PMID- 16625308
TI  - Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama,
      Japan.
AB  - Social object play (SOP), i.e., social play using portable object(s), among young
      Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was
      studied using a modified sequence sampling method from July to October 2000. SOP
      was a relatively common activity for most of the young macaques and often
      continued for long periods. Participants used many kinds of object, including
      edible natural objects and artificial objects, such as plastic bottles, but they
      never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts
      (>/=0.5 min) revealed the following interactive SOP features: (1) at any given
      time, participants used only one object, and only one participant held the
      object; (2) during SOP play-chasing, the object holder was likely to be chased by
      others; (3) during long bouts, the object changed hands frequently; and (4)
      agonistic competition for an object among young macaques was rare. Combinations
      of sexes, ages, relative ranks, or matrilines of the object holder and non-holder
      did not affect the tendency that the holder was chased by non-holder(s) during
      play-chasing. Even when there was a change in object holders, the repetitiveness
      of this interactive pattern, i.e., that the holder would be chased during SOP
      bouts, distinguished the SOP structure from that of other types of social play
      without object(s). General proximate social play mechanisms, such as self
      handicapping or role taking, were associated with SOP. Other mechanisms that
      affected SOP included the following: (1) young macaques treated an object as a
      target in play competition, and (2) 'being the holder of a target object' was
      associated with the 'role of the chasee.'

PMID- 16625309
TI  - Social organization of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) in
      the Qinling Mountains, Central China.
AB  - Sichuan snub-nosed monkeys were observed for 197 days from 2000 to 2003 in the
      Qinling Mountains, Central China. The study group was provisioned in 2001
      allowing detailed observations of social organization based on individual
      identification. The group was composed of 45-82 monkeys, all of which belonged to
      one of 6-8 one-male units (OMU) that foraged to form one big group. The average
      unit size was 9.0+/-2.3, 8+/-1.5 in the winter and 11.1+/-2.0 in the spring.
      Immigration or emigration of one-male units to or from the foraging group was
      observed, as was migration of individuals in and out of OMU, especially for by
      subadult females and juveniles. Group size therefore tended to fluctuate with the
      number of OMU and the number of young monkeys present in the group. The OMU in
      the study area were smaller than those in Shennongjia area. The factors
      influencing the size of these OMU and the entire group are discussed.

PMID- 16625310
TI  - Urinary incontinence symptoms during and after pregnancy in continent and
      incontinent primiparas.
AB  - OBJECTIVE: Examine patterns of urinary incontinence during and after pregnancy,
      as recalled by incontinent and continent primiparas. STUDY DESIGN: Primiparous
      women reporting no pre-pregnancy incontinence, were recruited 6 to 9 months
      postpartum. Those reporting current continence and demonstrating a negative
      stress test were considered "Primiparous Continent" (PC, n=64). Those reporting
      current incontinence and demonstrating a positive stress test were considered
      "Primiparous Incontinent" (PI, n=57). Subjects self-administered a questionnaire
      recalling leakage during and after pregnancy. RESULTS: Sixteen percent of PC
      women leaked during pregnancy. Of these, 70% experienced frequent leakage during
      pregnancy. Seventy-eight percent of PI women leaked both during and after
      pregnancy. Several patterns arose surrounding leakage frequency for PI women: 19%
      only leaked frequently during pregnancy, 4% only leaked frequently after
      pregnancy, and 51% leaked frequently both during and after pregnancy. CONCLUSION:
      Nearly five times as many primiparous incontinent women, compared with
      primiparous continent women, leaked during pregnancy.

PMID- 16625311
TI  - Reductions in overactive bladder-related incontinence from pooled analysis of
      phase III trials evaluating treatment with solifenacin.
AB  - The embarrassment and social stigma associated with urinary incontinence (UI) in
      overactive bladder syndrome (OAB) sufferers is a major reason for individuals to
      seek help for their condition. An analysis of 1,873 subjects with OAB with UI was
      conducted to assess the efficacy of solifenacin in reducing incontinence in a
      pooled population from four phase III clinical trials, stratified by severity of
      incontinence, urgency, and other key factors at baseline. Subjects were
      randomized to either 5 or 10 mg of solifenacin once daily or placebo for 12
      weeks. More than 50% of the total population became continent at study end, with
      either dose of solifenacin (P<0.01 vs placebo). Significant reductions in
      incontinence episodes and higher rates of attainment of continence vs placebo
      were observed irrespective of age or severity of incontinence or urgency at
      baseline with solifenacin treatment. Treatment was well tolerated, with the
      majority of adverse events being mild in nature. Solifenacin is an effective
      antimuscarinic agent for the treatment of incontinence associated with OAB.

PMID- 16625312
TI  - Evaluation of pericardial hydatid cysts by different echocardiographic imaging
      modalities.
AB  - Cardiac hydatid disease or echinococcosis is a rare complication of Echinococcus
      granulosus infection. Traditionally, the diagnosis is made with two-dimensional
      transthoracic echocardiography. This case report shows the complementary function
      of the different echo modalities (two-dimensional, three-dimensional, and
      contrast echocardiography) and MRI in the evaluation of pericardial hydatid cyst.

PMID- 16625313
TI  - Multifocal coronary artery myocardial bridging involving the right coronary and
      left anterior descending arteries detected by ECG-gated 64 slice multidetector CT
      coronary angiography.
AB  - Myocardial bridging is a congenital condition in which a segment of a major
      epicardial coronary artery has an intramyocardial course. Myocardial bridging is
      usually confined to a single vessel (typically the mid segment of the left
      anterior descending artery) and is usually asymptomatic, however, bridging may be
      associated with chest pain, myocardial infarction, or sudden cardiac death. While
      more commonly identified at autopsy, myocardial bridging is occasionally
      diagnosed by coronary angiography with identification of concomitant myocardial
      bridging involving both the left and right coronary arteries appearing to be
      uncommon. We present three patients presenting with atypical chest pain symptoms
      in whom concomitant right coronary artery and left anterior descending artery
      myocardial bridging was identified by ECG gated multidetector computed tomography
      (MDCT).

PMID- 16625316
TI  - Complete human gene structure of obscurin: implications for isoform generation by
      differential splicing.
AB  - The complete gene giant muscle protein obscurin, a modular protein composed
      largely of tandem Ig-domains, GDP/GTP exchange factor domains (GEF) for small G
      proteins, and differentially spliced kinase domains, was analysed. The splice
      donor and acceptor sites of the 117 exons give important clues for potential
      splice pathways. The fusion of the conventional obscurin A, containing only the
      GEF domain, and obscurin B, fusing into the 3' kinase exons, was experimentally
      confirmed and analysed. The linker between the two kinases contains multiple
      predicted phosphorylation sites, as well as a predicted NFX zinc finger domain.
      Both kinases show only weak homology to either myosin light chain kinases or
      other giant muscle protein kinases, suggesting that they are functionally
      distinct.

PMID- 16625317
TI  - Obscurin: a multitasking muscle giant.
AB  - Obscurin (approximately 800 kDa) is the third member of a family of giant
      proteins expressed in vertebrate striated muscle, along with titin (3-3.7 MDa)
      and nebulin (approximately 800 kDa). Like its predecessors, it is a multidomain
      protein composed of tandem adhesion modules and signaling domains. Unlike titin
      and nebulin, which are integral components of sarcomeres, obscurin is
      concentrated at the peripheries of Z-disks and M-lines, where it is appropriately
      positioned to communicate with the surrounding myoplasm. This unique distribution
      allows obscurin to bind small ankyrin 1, an integral component of the
      sarcoplasmic reticulum (SR) membrane. Obscurin also associates with the
      contractile apparatus through its binding to titin, sarcomeric myosin and perhaps
      other proteins of the contractile apparatus. Overexpression of the COOH-terminus
      of obscurin in primary myotubes has a dramatic and specific effect on the
      organization of sarcomeric myosin, indicating a role in the organization and
      regular assembly of A-bands. Given its ability to associate tightly, selectively
      and periodically with the periphery of the myofibril, its high affinity for an
      integral membrane protein of the SR and its close association with thick
      filaments, we speculate that obscurin is ideally suited to play key roles in
      modulating the organization and assembly of both the myofibril and the SR.

PMID- 16625319
TI  - Factors associated with abnormal eating attitudes among female college students
      in Japan.
AB  - OBJECTIVES: To determine the prevalence rates of abnormal eating attitudes and
      associated risk factors among female Japanese college students. SUBJECTS AND
      METHODS: The study population was 7812 female college students in Tokyo. They
      were asked to fill out the Japanese version of EAT-26 and lifestyle
      questionnaires. RESULTS: 5.1% of the subjects had a total EAT-26 score above the
      cutoff point (>20). Multiple regression analysis found the most important factors
      associated with abnormal eating attitudes were distorted body image, fewer
      sleeping hours, irregular meal habits, cigarette smoking and more exercise.
      DISCUSSION: The prevalence of abnormal eating attitudes among female college
      students in this study was lower than that of Japanese female high school
      students and lower than that reported for college students of both western and
      non-western countries. Our results suggest that body image dissatisfaction may be
      the most important factor associated with abnormal eating behavior.

PMID- 16625320
TI  - Transcriptional control of the HERV-H LTR element of the GSDML gene in human
      tissues and cancer cells.
AB  - Long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) have been
      reported to serve as alternative promoters in functional genes. The GSDML
      (gasdermin-like protein) gene located on human chromosome 17q21 has been found to
      be an oncogenomic recombination hotspot. Here, we identified the LTR element of
      HERV-H with reverse orientation as an alternative promoter of the GSDML gene and
      analyzed its expression pattern in human tissues and cancer cells. A reporter
      gene assay of the promoter activity of the LTR on the GSDML gene in human cancer
      cell lines (HCT-116 and HeLa) and a kidney cell line (Cos7) of African green
      monkey indicated that the LTR promoter with reverse orientation had stronger
      promoter activity than forward one. The transcripts of this LTR-derived promoter
      were widely distributed in various human tissues and cancer cells, whereas the
      transcripts of the cellular promoter were found only in stomach tissues and some
      cancer cells (HCT116, MCF7, U937, C-33A, and PC3). These findings suggest that
      the LTR element on the GSDML gene was integrated into the hominoid lineage and
      acquired the role of transcriptional regulation of human tissues and cancer
      cells.

PMID- 16625321
TI  - Comparative sequence analysis of envelope protein genes of Indian buffalopox
      virus isolates.
AB  - Buffalopox virus (BPXV) is considered to be a close variant of vaccinia virus
      (VACV), the prototype member of the genus Orthopoxvirus. In the present study, we
      have analyzed the sequences of H3L, A27L, and D8L gene-homologues of VACV in BPXV
      to elucidate its genetic relationship to VACV and other orthopoxviruses (OPVs).
      Products of these genes have been shown to be important in attachment of VACV to
      host cell surface receptors during viral entry. Additionally, the A27L gene is
      also responsible for cell fusion during infection, while the H3L gene is required
      for synthesis of the highly immunogenic major envelope protein p35. Full-length
      nucleotide sequences of H3L, A27L, and D8L genes of three BPXV isolates were
      determined by PCR amplification, cloning, and sequencing. The nucleotide (nt)
      sequence and the deduced amino acid (aa) sequences were compared with published
      sequences from other members of the genus Orthopoxvirus. Comparative sequence
      analysis of all the three genes revealed high sequence identity of BPXV isolates
      with VACV (close to 99% sequence identity) at both the nt and aa level.
      Phylogenetic analysis based on the deduced aa sequences of the H3L, A27L, and D8L
      genes also showed that BPXVs are more closely related to VACV than to any of the
      other OPVs.

PMID- 16625322
TI  - PrP(Sc) deposition in nervous tissues without lymphoid tissue involvement is
      frequently found in ARQ/ARQ Sarda breed sheep preclinically affected with natural
      scrapie.
AB  - The pathogenesis of natural scrapie in Sarda breed sheep was investigated in 1050
      asymptomatic and 49 sick sheep from scrapie-affected flocks. Central and
      peripheral nervous system, along with lymphoreticular system (LRS) tissues, were
      subjected to immunohistochemistry (IHC) and Western-blotting (WB) for detection
      of pathological isoform of the prion protein (PrP(Sc)). A total of 69 of the 1050
      clinically healthy sheep were found to be infected with scrapie, with PrP(Sc)
      being detected in both the central nervous system (CNS) and enteric nervous
      system (ENS) plexuses of 60 of the sheep, while IHC and WB yielded evidence of
      (PrP(Sc)) deposition only in lymphoid tissues of the remaining 9 clinically
      healthy sheep. PrP(Sc) was also detected in the CNS, as well as in ENS plexuses
      from all of the 49 clinically affected sheep. Nevertheless, 18 of the 69
      clinically healthy animals (26%, 17 ARQ/ARQ and 1 ARQ/AHQ sheep), along with 3
      ARQ/ARQ sheep (6%) of the clinically affected group, showed no IHC or WB evidence
      of PrP(Sc) in lymphoid tissues, but PrP(Sc) could be still detected in their CNS
      and ENS plexuses. The study demonstrates dual CNS and ENS PrP(Sc) deposition in
      Sarda sheep with scrapie, in spite of an apparent lack of lymphoid tissue
      involvement in a number of cases.

PMID- 16625323
TI  - Recurrent severe postoperative bleeding after stapled hemorrhoidopexy requiring
      emergency laparotomy.

PMID- 16625325
TI  - Mucosal flap excision for treatment of remnant prolapsed hemorrhoids or skin tags
      after stapled hemorrhoidopexy : Dis Colon Rectum 2005; 48:1660-1662.

PMID- 16625326
TI  - Perineal reconstruction after total pelvic evisceration and excision of
      pelviperineal soft tissues for recurrent vulvar carcinoma.

PMID- 16625329
TI  - Significance of histologic type of primary lesion and metastatic lymph nodes as a
      prognostic factor in stage III colon cancer.
AB  - PURPOSE: This study was designed to investigate whether the histologic types of
      the primary lesion and of metastatic lymph nodes in Stage III colon cancer are
      useful as prognostic factors. The usefulness of adjuvant chemotherapy in a
      randomized, controlled trial by using these prognostic factors as stratification
      criteria was also investigated. METHODS: Stage III colon cancer patients were
      enrolled and were divided into two groups: Group W, in which the histologic type
      of both primary tumors and metastatic lymph nodes was well-differentiated
      adenocarcinoma; and Group U, in which the primary tumors and the metastatic lymph
      nodes were of any type other than well-differentiated. Group W patients were
      assigned to Treatment Arm A (surgery alone) or Arm B (surgery, then 1
      hexylcarbamoyl-5-fluorouracil); and Group U patients, to Treatment Arm C (same as
      B), and Arm D (surgery + 1-hexylcarbamoyl-5-fluorouracil + mitomycin C). RESULTS:
      The Group W five-year survival rate was significantly superior to that in Group U
      (P = 0.0035). There was a better survival rate in Treatment Arm A than Arm B (P =
      0.0321), but no difference between Treatment Arms C and D. CONCLUSIONS: In Stage
      III colon cancer, the prognosis of cases whose primary lesion and lymph node
      tissues are both well differentiated is extremely good. In such cases, it is
      possible for adjuvant chemotherapy to have a deleterious effect, and therefore,
      it is not recommended.

PMID- 16625334
TI  - Gastrostomies in palliative care.
AB  - OBJECTIVE: In palliative care, gastrostomies are used to provide nutritional
      support or to decompress the bowel. To evaluate what happened to the patients
      monitored at our palliative care unit (PCU) who underwent gastrostomy between
      October 1994 and January 2005, a retrospective audit was made. METHOD: The charts
      of 154 patients were reviewed. RESULTS: The most frequent reason why a patient
      underwent a gastrostomy was dysphagia due to head and neck and/or esophageal
      cancer. Only one patient underwent a drainage gastrostomy because of intestinal
      obstruction. Interventional radiology performed 96% of the gastrostomies. Early
      complications occurred in 53 patients (34%) who underwent the gastrostomy for
      feeding and the most common was local pain, usually mild. However, there was one
      death due to peritonitis, probably related with the procedure. Late complications
      also occurred in 53 patients and major complications occurred in 22 patients, the
      most common was extrusion. The median survival after the performance of the
      gastrostomy was 61 days (range 1 to 551 days). Nineteen patients (12%) survived 1
      week or less, 28 (18%) between 8 and 30 days, 51 (33%) from 31 to 90 days, 53
      (35%) 91 days or more, and one unknown. The patient who underwent a gastrostomy
      for bowel obstruction survived for only 7 days. One hundred and twenty-five
      patients (81%) died at the PCU, 26 (17%) at home, and four (3%) at other places.

PMID- 16625335
TI  - Pilot study of a self-administered stress management and exercise intervention
      during chemotherapy for cancer.
AB  - GOALS OF WORK: This pilot project explored the feasibility, safety, and
      effectiveness of a self-administered exercise and stress management intervention
      for cancer patients receiving chemotherapy. PATIENTS AND METHODS: Thirty-nine of
      56 eligible patients (acceptance =69%) with a variety of solid tumors volunteered
      for the study. Participants were advised to exercise 20-40 min at 50-75%
      estimated heart rate reserve 3-5 times per week. In addition, patients were
      provided with instruction and written materials regarding stress management
      techniques. Follow-up data were collected during regularly scheduled outpatient
      visits at the start of the second, third, and fourth chemotherapy cycles using
      diary entries and the same questionnaires previously administered at baseline.
      MAIN RESULTS: Twenty-four of 39 patients (62%) completed all study requirements.
      These participants completed 438 of the 678 exercise sessions assigned (adherence
      =62%). Of the stress management techniques, positive thinking most practiced most
      frequently (48%), followed by deep breathing (38%) and active relaxation (37%).
      Paired t tests, comparing baseline values with final recorded values, indicated a
      significant improvement over time in bodily pain (p<0.03) and mental health
      (p<0.04) subscale scores. Participants' evaluations of the combined intervention
      were favorable: 90% felt it was helpful to them and 100% would recommend it to
      another patient. CONCLUSIONS: A self-administered intervention combining aerobic
      exercise and stress management was acceptable and safe for cancer patients
      receiving chemotherapy. Preliminary data demonstrating intervention efficacy
      should be confirmed in subsequent randomized clinical trials.

PMID- 16625337
TI  - Genital sympathetic skin responses in fibromyalgia syndrome.
AB  - The study was designed to investigate the autonomic dysfunction in fibromyalgia
      syndrome (FMS) by recording sympathetic skin response (SSR) from palmar, plantar
      and genital regions. The second aim was to evaluate the relation between sexual
      problems and autonomic dysfunction in FMS. SSR potential was recorded from
      palmar, plantar and genital regions in 28 married, female FMS patients and 18
      married, healthy females. Fibromyalgia Impact Questionnaire (FIQ) was used to
      show the clinical severity and functional disability in FMS patients. Glombok
      Rust Inventory of Sexual Satisfaction (GRISS), a 28-item questionnaire, was used
      to assess the existence and severity of sexual problems. Beck test was used to
      evaluate anxiety and depression. The amplitude of SSR recorded from palmar,
      plantar and genital regions was lower than in the control subjects (P < 0.05).
      GRISS (total and subscale), Beck test and FIQ scores of FMS patients were higher
      than in the control subjects (P < 0.05). No correlation was found between the SSR
      potential and GRISS scores. The results of our study reveal that abnormality in
      SSR recorded from palmar, plantar and genital regions reflects the abnormality in
      the autonomic nervous system (ANS) of FMS patients. These patients have more
      sexual problems than healthy subjects, and we think this finding is related to
      increased anxiety and depression in these patients.

PMID- 16625338
TI  - Massive cutaneous follicular lymphoid hyperplasia in a patient with the Sjogren
      syndrome: 7-year follow-up and immunohistochemical study.
AB  - The Sjogren syndrome often gives rise to complications such as pseudolymphomas
      and/or mucosa-/skin-associated lymphocytic tumors (MALT/SALT lymphomas). This
      paper presents a 74-year-old female patient with the Sjogren syndrome complicated
      by cutaneous plaques/tumors as cutaneous lymphoid hyperplasia over a 7-year
      follow-up study period. Immunohistochemical examination disclosed B-cell rich
      lymphoid follicle formation in the skin with the presence of T and B cells and a
      varied assortment of features to include abundant plasma cell infiltration. Based
      on the clinical course and histopathological findings, patient condition was
      considered benign and arises from reaction toward certain unknown microbes.

PMID- 16625339
TI  - Correlation between serum prolactin levels and lupus activity.
AB  - To assess the frequency of hyperprolactinemia and evaluate its possible clinical
      significance in patients with systemic lupus erythematosus (SLE). We determined
      serum prolactin (PRL) levels in 30 patients with SLE by a radioimmunometric
      assay. For each patient, the clinical disease activity was assessed using the
      Systemic Lupus Activity Measure. Antinuclear antibodies were determined by
      standard techniques. Correlation between PRL concentrations and SLE clinical and
      serological activity were evaluated. Elevated serum concentrations of PRL (>25
      ng/ml in female and >16 ng/ml in male) were found in 10 of the 30 (33.3%)
      patients (7-85 ng/ml, mean 33.8, SD 19.8). A significant correlation was found
      between the PRL levels and the clinical disease activity of SLE (P < 0.001, r =
      0.675). In addition, hyperprolactinemia was associated with serological activity.
      Hyperprolactinemia was frequently detected in patients with SLE. There is a
      significant correlation between hyperprolactinemia and lupus activity.

PMID- 16625340
TI  - Microscopic polyangiitis histologically confirmed by biopsy from nasal cavity and
      paranasal sinuses: a case report.
AB  - Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis affecting
      small vessels without necrotizing granulomatous inflammation and is commonly
      associated with necrotizing glomerulonephritis. Diagnosis is based on typical
      clinical features, the presence of antimyeloperoxidase-antineutrophil cytoplasmic
      antibodies (MPO-ANCA), and histopathologic findings. Cases of pathologically
      proven small-vessel vasculitis in nasal biopsy specimens are sparse. Here we
      report a patient with MPA that was histopathologically confirmed by nasal and
      paranasal biopsy. A 67-year-old man presented with fever and general fatigue.
      Laboratory examinations showed severe inflammation and acute progressive renal
      failure. The serum MPO-ANCA level was elevated. The patient also had nasal polyps
      that seemed to be nonspecific chronic sinusitis. To obtain a pathologic
      diagnosis, bilateral ethmoidectomy and nasal polypectomy were performed.
      Pathological findings revealed vasculitis of small vessels in the mucosal
      surface. MPA was diagnosed on the basis of clinical symptoms, elevated MPO-ANCA
      and the pathological findings of the nasal and paranasal surgical specimen.

PMID- 16625341
TI  - Antiphospholipid syndrome accompanied by a silent splenic infarct in a patient
      with juvenile SLE.

PMID- 16625342
TI  - The relation between joint erosion and generalized osteoporosis and disease
      activity in patients with rheumatoid arthritis.
AB  - The aim of this study is to investigate the correlation between joint erosion and
      osteoporosis in patients with rheumatoid arthritis (RA). Fifty-one patients with
      RA were included for the study. Hand radiograms of all patients were evaluated by
      the Larsen modified Sharp and carpometacarpal ratio methods. Bone mineral density
      (BMD) measurements were performed at the femur, lumbar, and forearm regions.
      Disease activity was assessed clinically by the health assessment questionnaire
      (HAQ), visual analog scale, erythrocyte sedimentation rate, C-reactive protein
      (CRP), and the rheumatoid factor (RF). There was no statistically significant
      difference in terms of the BMD values at L1-4 between the patients with RA and
      the control group. The BMD measurements at the right forearm and the right hip
      were statistically significantly lower in the patient group. For radiological
      scoring, hand radiograms were evaluated by three different methods. There was a
      significant correlation between the duration of disease and the radiological
      evaluation methods. HAQ scores, Larsen and Sharp methods 1/3 distal and mid
      distal (MID), and BMD measurements of the forearm were correlated. Moreover, 1/3
      distal, MID, and ultra-distal BMD showed significant correlations with CRP
      levels. Radiogram continues to have an important role in determining and
      following-up the joint erosion seen in patients with RA. However, we believe that
      as establishing periarticular osteoporosis in the early term by performing BMD
      measurements on the forearm is correlated with disease activity, it may be useful
      in the early diagnosis of RA and its objective results will be efficient in
      predicting the progression of disease.

PMID- 16625344
TI  - Evaluation of femoral head vascularization in slipped capital femoral epiphysis
      before and after cannulated screw fixation with use of contrast-enhanced MRI:
      initial results.
AB  - In this study we used contrast-enhanced magnetic resonance imaging (MRI) to
      evaluate the vascularization of the femoral head in children with slipped capital
      femoral epiphysis (SCFE) before and after cannulated screw fixation. Eleven
      consecutive children with SCFE, seven boys and four girls, aged 10-15 years were
      included in the study. There were no preslips; four children had acute, three
      acute-on-chronic, and four chronic SCFE. The MRI examinations were performed in a
      1.5 Tesla MR scanner with use of a coronal STIR sequence, a coronal contrast
      enhanced T1-weighted spin-echo sequence, and a sagittal three-dimensional
      gradient-echo sequence. Morphology, signal intensities, and contrast-enhancement
      of the femoral head were assessed by two radiologists in consensus. Morphologic
      distortion of the physis, bone marrow edema within the metaphysis and epiphysis,
      and joint effusion were the preoperative MRI findings of SCFE in each child. In
      nine children, the vascularization of the femoral head before and after surgery
      was normal. In one child, a preoperative avascular zone in the superolateral
      aspect of the epiphysis revascularized completely after surgery. One child with
      severe SCFE developed avascular necrosis of the femoral head after open reduction
      of the slip. We conclude that MRI allows for accurate evaluation of the femoral
      head vascularization before and after surgery in children with SCFE.

PMID- 16625346
TI  - Fusion of the midplane with the left intersectional plane: a liver anatomical
      variation revisited with multidetector-row CT.
AB  - This article updates the description of an anatomical variation of the liver, in
      which the gallbladder is adjacent to the ligamentum teres, that was described
      until now as "right-sided ligamentum teres and right umbilical portion of the
      portal vein". A study of eight patients showing this anatomical variation has led
      to a new archetypal anatomical description of the hepatic and portal veins, using
      multidetector-row computed tomography (MDCT) with three-dimensional (3D) volume
      rendering (VR) reconstructions. While 2D axial imaging gave the same information,
      MDCT imaging with VR reconstructions provided a clear 3D visualization of this
      anatomical variation. Typical features can be described as follows: (1)
      juxtaposition of the ligamentum teres and the gallbladder; (2) typical portal
      vein branching with a right posterior branch, a left posterior branch and a main
      medial branch that terminates in the ligamentum teres; (3) two main hepatic veins
      and a hypotrophied medial hepatic vein. We think, based on the direct comparison
      of anatomical findings and knowledge of chronological embryological development,
      that this abnormality results from the defective development of the central part
      of the liver and not from the persistence of the right rather than the left
      umbilical vein. Because of the presence of only one medial plane, containing both
      the gallbladder and the ligamentum teres, we propose renaming it "fusion of
      hepatic planes".

PMID- 16625347
TI  - CT-guided interstitial brachytherapy in the local treatment of extrahepatic,
      extrapulmonary secondary malignancies.
AB  - The purpose was to evaluate the safety and efficacy of high-dose-rate (HDR) CT
      guided interstitial brachytherapy in the treatment of extrahepatic,
      extrapulmonary, secondary malignancies. Nineteen patients were included in this
      prospective study. The median age was 66 years (49-77). Underlying primaries
      comprised colorectal carcinomas in six, renal cell carcinoma in three, pancreatic
      carcinoma in three, cervical cancer in two, endometrial cancer in two and NSCLC,
      breast cancer and sarcoma in one patient each. All patients had undergone
      extensive pretreatments. CT-guided HDR brachytherapy employed a 192Iridium
      source. Dose planning for brachytherapy was performed using 3D CT data acquired
      after CT-guided percutaneous applicator positioning. MRI follow-up was performed
      6 weeks and every 3 months post intervention. Primary endpoints were
      complications, local tumor control and progression-free survival. The median
      tumor diameter was 6 cm (2-15 cm). Tumor locations included the hepatoduodenal
      ligament, mesentery, adrenal gland, mesogastrium and local recurrences after
      rectal or pancreatic cancer. The minimal median dose in the target volume was 11
      Gy (4-18 Gy). Minor complications comprised pain and fever (n=6, 32%). Major
      complications included one hospital death of unknown causes (n=1; 5%). Median
      follow-up was 7 months (1-16). Four patients (21%) died during the follow-up
      period. Local tumor control was 76.5% after 6 months and progression-free
      survival 47% after 6 months. Minimally invasive CT-guided HDR brachytherapy is
      safe and effective in the palliative treatment of extrahepatic, extrapulmonary
      secondary malignancies.

PMID- 16625348
TI  - Pictorial review: magnetic resonance imaging of colonic diverticulitis.
AB  - Magnetic resonance imaging (MRI) is rapidly emerging as a useful imaging modality
      for the evaluation of the gastrointestinal tract. Increasingly rapid sequences
      and improving hardware have significantly improved the visualisation of diseases
      of the colon. MRI has a major advantage over CT in that there is no ionising
      radiation. In our institution, MRI has increasingly been used as a complimentary
      imaging modality to CT in the diagnosis and evaluation of diverticulitis and its
      complications. In this review article, we illustrate the emerging role of MRI in
      the diagnosis and evaluation of colonic diverticulitis.

PMID- 16625349
TI  - Characterization of the peri-infarction zone using T2-weighted MRI and delayed
      enhancement MRI in patients with acute myocardial infarction.
AB  - To characterize the peri-infarction zone using T2-weighted (T2w) magnetic
      resonance imaging (MRI) and infarct size on delayed enhancement (DE) MRI in
      patients with acute myocardial infarction (AMI). In 65 patients, short-axis T2w
      and DE MRI images were acquired 5 +/- 3 d after AMI. The MRI was analyzed using a
      threshold method defining infarct size on DE MRI and edema on T2w MRI as areas
      with signal intensity larger than +2 SD above remote normal myocardium. The peri
      infarction zone was calculated as the difference between the size of edema and
      the infarct size. The size of edema on T2w MRI (31.3 +/- 13.4% of LV area) was
      larger than the infarct size on DE MRI (20.3 +/- 10.4% of LV area, p< 0.0001).
      The size of the peri-infarction zone was 11.0 +/- 10.0% of the LV area. Good
      correlation was found between infarct size on DE MRI and peak creatine kinase
      (CK) isoenzyme MB (r = 0.65, p< 0.0001), but there was no correlation between the
      size of the peri-infarction zone and CK MB (r = 0.05, p = 0.67). The peri
      infarction zone was larger in patients with an infarct size <28% of the LV area
      (12.6 +/- 10.0% LV area) compared with patients with an infarct size > or =28% of
      the LV area (6.7 +/- 9.0% of the LV area, p< 0.05). The peri-infarction zone does
      not correlate with enzymatic parameters of infarct size and is substantially
      larger in small infarcts, indicating viable myocardium.

PMID- 16625350
TI  - Functional MRI for immediate monitoring stereotactic thalamotomy in a patient
      with essential tremor.
AB  - The effect of stereotactic thalamotomy was assessed with pre- and postoperative
      functional magnetic resonance imaging (fMRI) under motor stimulation. A patient
      with unilateral essential tremor (ET) of the left arm underwent stereotactically
      guided thalamotomy of the right ventral intermediate thalamic nucleus (VIM). FMRI
      was done directly before and after surgery on a 1.5-Tesla scanner. The
      stimulation paradigm was maintainance of the affected arm in an extended position
      and hand clenching being performed in a block design manner. Statistical analysis
      was done with Brain Voyager 2000. After thalamotomy the tremor diminished
      completely. As a difference between the pre- and postoperative fMRI, a
      significant activation was found in the VIM contralateral to the activation site,
      adjacent to the inferior olivary nucleus contralateral to the activation site and
      in the dorsal cingulum. In conclusion, fMRI can detect the functional effect of
      thalamotomy for tremor treatment. Direct postoperative fMRI provides a sufficient
      method for estimating the effect of thalamotomy immediately after intervention.
      The importance of the intermediate thalamic nucleus and the olivary nucleus in
      tremor generation is supported by our findings.

PMID- 16625352
TI  - MRI features of neurodegenerative Langerhans cell histiocytosis.
AB  - CNS complications of LCH include "space occupying" lesions corresponding to
      histiocytic granulomas and "neurodegenerative" presentation (ND-LCH)
      characterized by a progressive cerebellar ataxia. Studies analyzing specifically
      the MRI presentation of ND-LCH are scarce. We present here the MRIs of 13
      patients registered as isolated ND-LCH. Posterior fossa was involved in 12
      patients (92%), showing a symmetrical T2 hyperintensity of the cerebellar white
      matter areas in seven cases with a circumscribed T1 hyperintensity of the dentate
      nuclei in five cases, definite hyperintense T2 areas in the adjacent pontine
      tegmentum white matter in nine cases associated with a hyperintensity of the
      pontine pyramidal tracts in four cases. A cerebellar atrophy was noted in eight
      cases. The supratentorial region was involved in 11 patients, showing T2
      hyperintense lesions in the cerebral white matter in eight cases and a discrete
      symmetrical T1 hyperintense signal in the globus pallidus in eight patients. A
      diffuse cortical atrophy was present in three cases and a marked focal atrophy of
      the corpus callosum in three cases. This series allows us to establish a not
      previously reported evocative semeiologic MR presentation to precisely orientate
      to the diagnosis of the pure neurodegenerative form of LCH.

PMID- 16625353
TI  - A carotenoid synthesis gene cluster from Algoriphagus sp. KK10202C with a novel
      fusion-type lycopene beta-cyclase gene.
AB  - A carotenoid synthesis gene cluster was isolated from a marine bacterium
      Algoriphagus sp. strain KK10202C that synthesized flexixanthin. Seven genes were
      transcribed in the same direction, among which five of them were involved in
      carotenoid synthesis. This cluster had a unique gene organization, with an
      isoprenoid gene, ispH (previously named lytB), being present among the carotenoid
      synthesis genes. The lycopene beta-cyclase encoded by the crtY ( cd ) gene
      appeared to be a fusion of bacterial heterodimeric lycopene cyclase CrtY(c) and
      CrtY(d). This was the first time that a fusion-type of lycopene beta-cyclase was
      reported in eubacteria. Heterologous expression of the Algoriphagus crtY ( cd )
      gene in lycopene-accumulating Escherichia coli produced bicyclic beta-carotene. A
      biosynthesis pathway for monocyclic flexixanthin was proposed in Algoriphagus sp.
      strain KK10202C, though several of the carotenoid synthesis genes not linked with
      the cluster have not yet been cloned.

PMID- 16625354
TI  - Global transcriptional analysis of Methanosarcina mazei strain Go1 under
      different nitrogen availabilities.
AB  - Certain archaeal species can fix molecular nitrogen under nitrogen limiting
      conditions although little is known about this process at either the genetic or
      molecular level. To address this on a genome-wide scale, transcriptional analysis
      was performed on the model methanogen Methanosarcina mazei strain Go1 using DNA
      microarrays. The genomic expression patterns for cells grown under nitrogen
      fixing conditions versus nitrogen sufficiency (10 mM ammonium) revealed that
      approximately 5% of all genes are differentially expressed. Besides a small set
      of genes previously known to be up-regulated under nitrogen limitation, 14
      additional genes involved in nitrogen metabolism were identified plus 10 genes
      encoding potential transcriptional regulators, 13 genes involved in carbon
      metabolism, 3 genes in general stress response, 8 putative transporter genes, and
      an additional 21 genes with unknown function. Quantitative reverse transcriptase
      PCR experiments confirmed the differential expression of a subset of these genes.
      Promoter analysis revealed a palindromic DNA motif centered nearby the
      transcriptional start point for several genes up-regulated under nitrogen
      limitation. A bioinformatics study demonstrated the presence of this motif in the
      up-stream region of 52 genes genome-wide, the majority of which showed nitrogen
      dependent differential transcription. We therefore hypothesize that this DNA
      element is involved in nitrogen control in M. mazei where it may act as a binding
      site for a regulatory protein.

PMID- 16625355
TI  - The Rhizobium leguminosarum regulator IrrA affects the transcription of a wide
      range of genes in response to Fe availability.
AB  - We show that an unusual transcriptional regulator, called IrrA, regulates many
      genes in the symbiotic N2-fixing bacterium Rhizobium leguminosarum in response to
      iron availability. Several operons in R. leguminosarum are expressed at lower
      levels in cells grown in Fe-depleted compared to Fe-replete medium. These include
      hemA1, which encodes the haem biosynthesis enzyme amino-levulinic acid synthase;
      sufS2BCDS1XA, which specify enzymes for FeS cluster synthesis; rirA, a global, Fe
      responsive transcriptional repressor; RL0400, which likely encodes an unusual FeS
      cluster scaffold; and the possible ferri-siderophore ABC transporter rrp1.
      Reduced expression in Fe-depleted medium was effected by IrrA, a member of the
      Fur super-family, which in Bradyrhizobium, the symbiont of soybeans, and in the
      mammalian pathogen Brucella, is unstable in Fe-replete conditions, due to an
      interaction with haem. The R. leguminosarum IrrA likely interacts with ICE (iron
      control element) motifs, conserved sequences near the promoters of its target
      genes. The rirA, sufS2BCDS1XA and rrp1 genes are also known to be regulated by
      RirA, which represses their expression in Fe-replete medium. We present a
      possible model for iron-responsive gene regulation in Rhizobium, in which the
      IrrA and RirA regulators, working in parallel, respond to the intracellular
      availability of haem and, possibly, of FeS clusters respectively. Thus, these
      regulators may sense the physiological consequences of extraneous Fe
      concentrations, rather than the concentration of Fe per se, as happens in those
      bacteria (e.g. Escherichia coli) in which the ferric uptake regulator Fur is the
      global Fe-responsive gene regulator.

PMID- 16625358
TI  - [Acute hypertension following dexamethasone. A critical incident during
      anesthesia].
AB  - Prior to anesthesia a 65-year-old patient received 8 mg dexamethasone to prevent
      postoperative nausea and vomiting (PONV). Instantly she reported tingling and
      burning followed by intense pain in the genital region spreading to the whole
      body. Shortly later she complained about shortness of breath and pre-cordial
      pain. Acute hypertension could only be lowered by NTG, beta-blockade and
      induction of anesthesia. The ECG showed ST-segment depressions and troponin-T was
      elevated (0.3 ng/ml). Coronary angiography revealed no significant stenosis and
      an abdominal CT scan showed no evidence of a pheochromocytoma. Urine metabolites
      of catecholamines were negative. Thus, the most likely diagnosis was stimulation
      of endogenous catecholamines by painful stress after dexamethasone injection with
      the consequence of myocardial ischemia. As a result we now routinely inject
      dexamethasone after anesthesia induction as prophylaxis for PONV.

PMID- 16625360
TI  - [Genetics, pain and analgesia].
AB  - Genomic variations influencing nociceptive sensitivity and susceptibility to pain
      conditions, as well as responses to pharmacotherapy of pain are currently under
      investigation. Candidate genes involved in pain perception, pain processing and
      pain management such as (opioid) receptors, transporters and other targets of
      pharmacotherapy are discussed. Drug metabolizing enzymes represent a further
      major target of ongoing research in order to identify associations between an
      individual's genetic profile and drug response (pharmacogenetics). Polymorphisms
      of the cytochrome P 450 enzymes influence analgesic efficacy of codeine, tramadol
      and tricyclic antidepressants (CYP2D6). Blood levels of some non-steroidal anti
      inflammatory drugs (NSAIDs) are dependent on CYP2C9 activity, whereas opioid
      receptor polymorphisms are discussed with respect to differences in opioid
      mediated analgesia and side-effects. Pharmacogenetics is seen as a potential
      diagnostic tool for improving patient therapy and care and will contribute to a
      more individualized drug treatment in the future.

PMID- 16625362
TI  - Body mass and composition responses to short-term low energy intake are
      seasonally dependent in Steller sea lions (Eumetopias jubatus).
AB  - Steller sea lions (Eumetopias jubatus) were fed restricted iso-caloric amounts of
      Pacific herring (Clupea pallasi) or walleye pollock (Theragra chalcogramma) for 8
      9 days, four times over the course of a year to investigate effects of season and
      prey composition on sea lion physiology. At these levels, the sea lions lost body
      mass at a significantly higher rate during winter (1.6 +/- 0.14 kg day(-1)), and
      at a lower rate during summer (1.2 +/- 0.32 kg day(-1)). Decreases in body fat
      mass and standard metabolic rates during the trials were similar throughout the
      seasons and for both diet types. The majority of the body mass that was lost when
      eating pollock derived from decreases in lipid mass, while a greater proportion
      of the mass lost when eating herring derived from decreases in lean tissue,
      except in the summer when the pattern was reversed. Metabolic depression was not
      observed during all trials despite the constant loss of body mass. Our study
      supports the hypothesis that restricted energy intake may be more critical to
      Steller sea lions in the winter months, and that the type of prey consumed (e.g.,
      herring or pollock) may have seasonally specific effects on body mass and
      composition.

PMID- 16625363
TI  - Structural themes and variations in protein kinase A as seen by small-angle
      scattering and neutron contrast variation.
AB  - Using small-angle solution scattering and neutron contrast variation, we have
      studied the structure of the multi-subunit protein kinase A. We have gained
      insights into how nature can take a set of common structural domains (or themes)
      and modulate their interactions via sequence variations and second messenger
      mediated signaling to affect enzyme activity and receptor binding important for
      targeting this multi-function enzyme to specific sub-cellular locations. These
      studies demonstrate the power of neutron contrast variation to expand our
      knowledge of the dynamic supra-molecular structures that carry out biological
      function.

PMID- 16625364
TI  - The common bile duct ligation in rat: A relevant in vivo model to study the role
      of mechanical stress on cell and matrix behaviour.
AB  - Common bile duct ligation leads to bile accumulation and liver fibrosis. In this
      model, little attention has been dedicated to the modification of the common bile
      duct. We have studied by histochemistry and immunohistochemistry, 3 and 5 days
      after ligation, the connective tissue modifications of the common bile duct wall.
      After bile duct ligation, compared with normal bile duct, a strong increase of
      the bile duct diameter, due to bile stasis, and a thickness of the bile duct wall
      were observed; numerous myofibroblasts expressing alpha-smooth muscle actin
      appeared in parallel with the detection of many proliferating connective tissue
      cells. These myofibroblasts secreted very early high amount of elastic fibre
      components, elastin and fibrillin-1. Elastic fibre increase was also observed
      close to the epithelial cell layer. Procollagen type III deposition was also
      induced 3 days after ligation but decreased thereafter, underlining that
      myofibroblasts modify their synthesis of extracellular matrix components to
      comply with the request. We show here that common bile duct ligation represents
      an invaluable model to study myofibroblastic differentiation and extracellular
      matrix adaptation produced by an acute mechanical stress.

PMID- 16625365
TI  - Immunohistochemical study of NG2 chondroitin sulfate proteoglycan expression in
      the small and large intestines.
AB  - The intestinal subepithelial myofibroblasts (ISEMFs) are located in the lamina
      propria under the epithelial cells. ISEMFs are thought to have an important role
      in protecting and maintaining the integrity of the epithelial cell layer and also
      in the process of wound healing. In this study, we report that the membrane-bound
      proteoglycan NG2 is abundantly distributed in the ISEMF layer of the mouse and
      human intestines. NG2 immunostaining in this layer is distributed with similar
      intensity from the crypt to villi. NG2 is also immunolocalized along the
      membranes of smooth muscle cells in the intestinal muscle layer. However,
      skeletal and cardiac muscles are not immunostained for NG2, demonstrating
      selective expression of the proteoglycan by smooth muscle cells. Using electron
      microscopy, NG2 immunoreactivity was strongly observed along the cell membranes
      of ISEMF, with weak diffusion into the neighboring matrix, indicative of the
      presence of some "shed" NG2. This first report of NG2 proteoglycan expression by
      ISEMF provides insights into the nature of the interaction of these cells with
      extracellular matrix and/or intestinal epithelial cells.

PMID- 16625366
TI  - Hypertrophic muscle fibers with fissures in power-lifters; fiber splitting or
      defect regeneration?
AB  - Power-lifters have hypertrophic muscle fibers with fissures seen in cross
      sections, called as fiber splitting. Whether this phenomenon is due to real
      splitting or defective regeneration has not been settled. To elucidate this
      matter,we have examined biopsies from the trapezius and vastus lateralis of power
      lifters (P group) and power lifters self-administrating anabolic steroids (PAS
      group). For this purpose, immunohistochemical staining of serial cross -sections
      was used. The PAS group had significantly more fibers with fissures than the P
      group in the vastus lateralis (1.2%+/-0.95% vs 0.35+/-0.34, P < 0.05) but not in
      the trapezius muscle (1.7% in both groups). Serial sections revealed that the
      fibers with fissures changed their profile profoundly over short distances. Some
      such fibers had a mature staining profile, whereas other fibers indicated recent
      degeneration and/or regeneration. Activation of satellite cells and formation of
      aberrant segments were also evident. We conclude that the so-called split fibers
      are due to defect regeneration. Some fibers with fissures are the results of old
      events of segmental muscle fiber damage, whereas the others reflect an ongoing
      process. The normal regenerative process is most likely disturbed in power
      lifters by their continuous training with repeated high mechanical stress on the
      muscles.

PMID- 16625367
TI  - Clathrin and clathrin-accessory proteins in rat kidney cortex epithelia.
AB  - Several vectorial transport routes in mammalian cells involve clathrin and
      associated proteins. In kidney epithelia urine production requires numerous
      transport processes. However, only little is known about the distribution of
      clathrin and its associated proteins in this organ in situ. We now report on the
      presence and distribution of clathrin and its accessory proteins AP1, AP2, Eps15,
      Epsin, CALM and Clint/EpsinR in the epithelia of the rat kidney cortex using
      immunoblotting, immunofluorescence and immuno-electron microscopy. Our data show
      that all investigated proteins are ubiquitously present in rat kidney cortex
      epithelia, however, with distinct distribution patterns. In the renal corpuscle,
      podocytes showed the most conspicuous labelling. Clathrin, AP2 and CALM were
      highly expressed in foot processes, while AP1 was primarily localized in the cell
      body. In the proximal tubule all proteins were present in dots along the plasma
      membrane and most conspicuous below the brush border. However, clathrin and AP2
      co-localized in vesicle subtypes distinct from those containing clathrin and AP1.
      In the distal tubule and in the cortical collecting duct all proteins were found
      in the apex of the cells; however, AP1 and Clint/EpsinR showed additional
      staining in perinuclear dots. The occurrence and distribution of the investigated
      proteins in kidney epithelia are discussed with respect to their possible
      involvement in the functions of the specific nephron segment.

PMID- 16625369
TI  - [Invasive aspergillosis of the skull base with orbit infiltration].
AB  - BACKGROUND: [corrected] Aspergillosis of the paranasal sinuses is subdivided into
      noninvasive and invasive types, depending on invasion of the tissue. The invasive
      form often occurs in immunodeficient patients and can be divided further into
      granulomatous, chronic invasive, and acute fulminating forms. CASE REPORT: We
      report the clinical course of an immunosuppressed 64-year-old male with invasive
      aspergillosis originating from the sphenoid sinus with infiltration of the orbit
      and intracranial extension into the cavernous sinus. The patient was referred to
      our hospital with loss of vision, ptosis, and ophthalmoplegia of 3-month
      duration. Additionally he suffered from diabetes mellitus II and kidney failure
      after kidney transplantation. After CT scanning, endonasal sinus debridement and
      decompression of the orbit were carried out immediately. Histology revealed
      invasive aspergillosis. Postoperatively, both systemic and local antimycotic
      therapy and antibiotic treatment were performed. According to recommendations of
      the Undersea and Hyperbaric Medicine Society, cerebral abscess is a certain
      indication of hyperbaric oxygenation. We decided to attempt therapy for that as
      well. The patient died 3 weeks after surgical intervention due to carotid
      dissection. CONCLUSION: Invasive aspergillosis of the paranasal sinuses and the
      skull base of immunsuppressed patients is usually lethal because of intracranial
      complications. Therefore, fast diagnosis using CT and MRI and surgical and
      antimycotic therapy are necessary.

PMID- 16625370
TI  - [Clinical efficiency and the influence of human factors on ear, nose, and throat
      navigation systems].
AB  - BACKGROUND: The aim of this study was to evaluate the Navibase navigation system
      for ear, nose, and throat (ENT) surgery. A new methodology for evaluating
      surgical and human factors is developed. PATIENTS AND METHODS: The evaluation is
      based on 102 ENT surgical applications, including 89 cases of functional
      endoscopic sinus surgery (FESS). The evaluation of surgical and human factors was
      performed by seven ENT surgeons. To evaluate surgical performance, level of
      quality (LOQ) in the 89 cases of FESS was determined, comparing the surgeon's own
      impressions with those of the navigation system on a scale from 0 to 100 and
      further comparing them with clinical results. Intraoperative changes in surgical
      strategy were documented. The human factors of total confidence (trust),
      situation awareness, skill set requirement and workload shift were recorded as
      level of reliance (LOR). RESULTS: The maximum deviation amounted to 1.93 mm.
      Averaging the quality of information resulted in an LOQ of 63.59. Every second
      application of the navigation system (47.9%) led to a change in surgical
      strategy. Total confidence showed a positive evaluation of 3.35 points in LOR.
      CONCLUSION: Application-relevant information relevant to the application beyond
      only technical details permits comparison with other assisting systems.

PMID- 16625371
TI  - [Isolated apical petrositis: an atypical case of Gradenigo's syndrome].
AB  - In 1904 Guiseppe Gradenigo described an infection of the apex of the petrous part
      of the temporal bone from acute otitis media with the clinical symptoms of
      unilateral pain around the eye, diplopia due to sixth nerve paralysis and
      persistant otorrhea. While this infection became evident by inward extension from
      petrositis in the majority of fatal cases from acute otitis media in the
      preantibiotic era, it has now become very rare. Today, cases mainly derive from
      cholesteatomas or chronic osteomyelitis of the petrous bone. However, due to
      intense antibiotic treatment in acute otitis media clinical signs of petrositis
      may be less typical compared to former times. We report on a 12-year-old boy with
      rapid onset of sixth nerve paralysis without clinical signs of acute otitis media
      or mastoiditis. CT and NMR imaging confirmed infection of the petrous apex. He
      was treated by mastoidectomy with exploration of a posterior cell group from the
      epitympanon around the semicircular canals and subsequent high dose intravenous
      antibiotics. The patient recovered without any loss of inner ear or facial nerve
      function. The paralysis of the sixth nerve disappeared completely within 6 weeks.

PMID- 16625372
TI  - ["Descending necrotizing mediastinitis" due to deep neck infections. Incidence
      and management].
AB  - BACKGROUND: "Descending necrotizing mediastinitis" (DNM) is a rare but
      potentially life-threatening complication of deep neck infections caused by the
      rapid downward spread of a oropharyngeal infection along the facial planes into
      the mediastinum. MATERIAL AND METHODS: Between June 1997 and December 2004, 6
      patients with DNM were treated in our department. The primary etiology was a
      peritonsillar abscess in 2 cases, a parapharyngeal abscess in 3 cases and in 1
      case an odontogenic abscess. Most patients presented with risk factors such as
      diabetes mellitus or alcoholism, the mean age was 44.3 years and the mean
      duration of signs before diagnosis was 6.3 days. Thoracotomy was associated with
      the cervical approach in 4 cases and tracheostomy was also performed in 4 cases.
      RESULTS: Four patients were successfully treated, the mean duration of
      hospitalisation was 48.2 days and 2 patients died from sepsis and multiorgan
      failure despite intensive treatment. CONCLUSIONS: Descending necrotizing
      mediastinitis must be detected as soon as possible. The mean symptoms are
      persistent complaints after treatment of oropharyngeal infections, which may be
      masked by analgetic treatment. Only an immediate computer tomographic scanning,
      aggressive surgical drainage and debridement of the neck and the mediastinum can
      reduce the high mortality rate.

PMID- 16625373
TI  - Perforated colonic cancer presenting as intra-abdominal abscess.
AB  - BACKGROUND AND AIMS: The various presentations of carcinoma of the colon are well
      known. Abscess formation occurs in 0.3 to 0.4% and is the second most common
      complication of perforated lesions. Perforation and penetration of adjacent
      organs with intra-abdominal abscess formation as the initial presentation is
      uncommon. MATERIALS AND METHODS: A retrospective analysis was made between
      January 1998 and December 2003 at the Kaohsiung Medical University Hospital. Six
      colon cancer patients with intra-abdominal abscess as the initial presentation
      were enrolled into this study. Among them, two were men and four were women.
      RESULTS: During the 6-year period, there were 756 patients with colonic carcinoma
      but only six of those patients (0.79%) presented with abscess formation as the
      initial finding. The initial pre-operative diagnosis was ruptured colonic
      diverticulitis with abscess formation in three patients, and the other three
      patients were as follows: one ruptured appendicitis with abscess, one right
      subcutaneous inguinal abscess, and one omphalitis with abdominal wall abscess.
      Subsequent colonoscopy was performed in two patients, and colon cancer was
      recognized. The most common associated symptoms/signs were palpable abdominal
      mass, abdominal pain, and anemia. All of them underwent a one-stage surgical
      procedure, and adjuvant chemotherapy was given. One patient died of peritoneal
      carcinomatosis and liver metastases 1 year post-operatively. The other five
      patients are still alive. CONCLUSIONS: It is difficult to make an accurate
      diagnosis of abscess formation as the first evidence of colonic carcinoma pre
      operatively. The one-stage resection of the lesion seems to be an acceptable
      treatment. For patients with intra-abdominal abscess, clinicians should be aware
      of this differential because it is easily ignored pre-operatively.

PMID- 16625374
TI  - Inflammatory bowel disease and the lung: is there a link between surgery and
      bronchiectasis?
AB  - PURPOSE: One-third of patients with inflammatory bowel disease (IBD) has
      extracolonic manifestations. Inflammatory bowel-associated pulmonary disease is
      one of the less commonly recognized and more recently described manifestations.
      Here, we report the experience of our patients with inflammatory bowel-associated
      bronchiectasis. METHODS: A retrospective analysis of case notes of patients with
      IBD and respiratory manifestations was undertaken. Relevant demographic,
      clinical, radiological, and pulmonary physiology laboratory results were
      reviewed. RESULTS: Ten patients with IBD and bronchiectasis were identified.
      Eight developed respiratory symptoms after surgery for IBD. Five of the ten had
      ulcerative colitis. Their lung function abnormality is mild to moderate in
      severity. Small airways disease (forced expiratory flow between 25-75% is <50%)
      was evident in seven of the ten patients. CONCLUSIONS: This preliminary study
      supports an association between surgery for IBD and development of symptomatic
      lung disease, particularly bronchiectasis, in susceptible patients. The pulmonary
      manifestations of IBD in some patients may only become clinically significant
      after surgery and the withdrawal of medical treatment.

PMID- 16625375
TI  - Cyanoacrylate glue in the treatment of ano-rectal fistulas.
AB  - BACKGROUND AND AIMS: The management of anal fistula is debatable. Although
      several procedures have been described, none of them is free from complications,
      such as anal incontinence and anal pain. The purpose of this study was to
      evaluate the employment of a glue composed of N-butil-2-cyanoacrylate and
      methacryloxysulfolane (Glubran 2) to treat fistula-in-ano. PATIENTS AND METHODS:
      Twenty-one patients (14 men and 7 women) with cryptoglandular anal fistula were
      enrolled in the study and treated as day-cases. Fistulas were assessed both
      clinically and by trans-rectal endosonography with a rotating 10-MHz 360 degrees
      endoscopic probe. Assessment of continence was also performed. The fistula tract
      was identified, curetted and washed-out with normal saline and hydrogen peroxide;
      then the glue was injected from the syringe nozzle through a catheter previously
      inserted into the fistula. Additional treatments were performed when the first
      failed. RESULTS: Five of seven simple fistulas (71.4%) healed with primary glue
      treatment; the other two needed second and third injections, and both healed. Ten
      of 14 (71.4%) complex fistulas healed with primary treatment; of the other four
      patients, one showed signs of intolerance to cyanoacrylate, which required re
      intervention to remove the applied glue. In the second patient, treatment was
      successful after a second session; in the third case, three glue injections were
      required; while the fourth patient was lost at follow-up after three unsuccessful
      sessions. The ratio of cumulative healing with only one treatment was 15/21
      (71.4%), and the ratio of overall healing after more than one session was 19/21
      (90.2%). There was no sign of recurrence of the disease after 18 months of follow
      up. CONCLUSION: Cyanoacrylate glue seems to be ideal to treat fistula-in-ano, as
      it is a safe, cost-effective, repeatable and muscle-sparing technique. The
      incidence of recurrence is low, and post-procedure complicated fistulas or
      perianal abscesses were not reported.

PMID- 16625376
TI  - Disseminated Klebsiella pneumoniae infection after hemorrhoidectomy.

PMID- 16625377
TI  - Prospective randomised trial comparing ileocaecal interposition and colon-J-pouch
      as rectal replacement after total mesorectal excision.
AB  - BACKGROUND: Ileocaecal interposition (ICI) is a technique of rectal replacement
      after total mesorectal excision (TME), but the method has never been evaluated in
      a randomised fashion. We performed a randomised, controlled trial to compare ICI
      and colon-J-pouch (CJP) for rectal replacements after TME for rectal cancer.
      MATERIALS AND METHODS: Fifteen patients were enrolled into each treatment group
      of the trial according to the protocol. Follow-up evaluations were performed 3
      months and 1 year after ileostomy closure and at a mean of 5 years after initial
      surgery. RESULTS: Similar results between the groups were found for incontinence,
      urgency, constipation and quality of life at all follow-ups. The frequency of
      defecation was slightly lower in the CJP group at 3 months [3 (2-6) vs 5 (2-11)
      (p=0.043)] and at 1 year [3 (2-5) vs 5 (2-8) (p=0.034)]. However, this difference
      lost significance if patients who had postoperative radiotherapy were excluded
      from the analysis. Four out of the 15 patients treated with ICI experienced bowel
      obstruction, which required open surgery in two, endoscopic dilatation in one or
      maintenance of the ileostomy in one patient. None of the patients treated with
      CJP had similar complications. CONCLUSIONS: ICI and CJP reconstruction result in
      a similar functional outcome and quality of life. As ICI did not show any benefit
      over CJP and tended to result in a higher frequency of defecation, it should not
      be used as a first choice treatment. In addition, ICI was associated with
      significant complications after radiotherapy. Therefore, it must not be used if
      postoperative radiochemotheray is intended.

PMID- 16625385
TI  - Efavirenz-induced urolithiasis.
AB  - We describe the first case of efavirenz-induced urolithiasis in a 47-year-old HIV
      positive patient. Urinary obstruction led to pyelonephritis and septic shock,
      requiring emergency ureteral catheterisation. The subsequent clinical course was
      favourable, allowing the patient's discharge on day 5. A 7 mm, radio-translucent,
      non-crystalline, beige stone was extracted during catheterisation. Stone analysis
      by Fourier transform infrared spectrometry, liquid chromatography and mass
      spectrometry revealed a stone composed of efavirenz (EFV) metabolites M4, M5, M8
      (as described by Mutlib et al. in 1999) and approximately 50% of unspecified
      proteins. EFV is a non-nucleoside reverse transcriptase inhibitor introduced to
      European markets in 1999. It is principally metabolised by cytochrome P450 3A4
      and 2B6. Of the dose, 14-34% is excreted in the urine, 1% as unchanged drug. The
      patient had been taking 600 mg EFV per day for 3 years. As EFV-induced
      urolithiasis has not been reported so far, we would like to draw the attention of
      the medical community to this potentially severe complication.

PMID- 16625393
TI  - Development of a compact anti-BAFF antibody in Escherichia coli.
AB  - Recombinant antibodies, especially single-chain antibody fragment (scFv), can be
      applied as detection reagents and even substitute for some reagents used in
      immunoassays. For scFv fragments, there is no such universal system available up
      to now. We have constructed vectors for the convenient, rapid expression of a
      novel compact antibody composed of anti-B-cell-activating factor of the TNF
      family (BAFF) scFv and the Fc portion (the hinge region, CH2, and CH3 domains) of
      the human IgG1 in Escherichia coli. After expression in bacteria as inclusion
      bodies, the recombinant antibody was purified and refolded in vitro. The scFv-Fc
      antibody was demonstrated to retain high binding affinity to antigen, including
      membrane-bound BAFF and soluble BAFF, and to possess some human IgG
      crystallizable fragment domain functions, such as human complement C1q and
      protein A binding. Both size-exclusion high-performance liquid chromatography
      column analysis and Western blotting of proteins subjected to nonreducing sodium
      dodecyl sulfate polyacrylamide gel electrophoresis suggested that scFv-Fc
      antibody is homodimeric with relative molecular mass of 110 kDa. These findings
      suggest that the compact antibody may be useful in diagnostic application for the
      prediction of BAFF relevant to autoimmune diseases in human.

PMID- 16625394
TI  - Isolation and characterization of polyunsaturated fatty acid producing
      Thraustochytrium species: screening of strains and optimization of omega-3
      production.
AB  - An isolation program targeting Thraustochytrids (marine fungoid protists) from 19
      different Atlantic Canadian locations was performed. Sixty-eight isolates were
      screened for biomass, total fatty acid (TFA), eicosapentaenoic acid (EPA), and
      docosahexaenoic acid (DHA) content. Analysis of fatty acid methyl ester results
      discerned four distinctive clusters based on fatty acid profiles, with biomass
      ranging from 0.1 to 2.3 g L(-1), and lipid, EPA, and DHA contents ranging from
      27.1 to 321.14, 2.97 to 21.25, and 5.18 to 83.63 mg g(-1) biomass, respectively.
      ONC-T18, was subsequently chosen for further manipulations. Identified using 18S
      rRNA gene sequencing techniques as a Thraustochytrium sp., most closely related
      to Thraustochytrium striatum T91-6, ONC-T18 produced up to 28.0 g L(-1) biomass,
      81.7% TFA, 31.4% (w/w biomass) DHA, and 4.6 g L(-1) DHA under optimal
      fermentation conditions. Furthermore, this strain was found to produce the
      carotenoids and xanthophylls astaxanthin, zeaxanthin, canthaxanthin, echinenone,
      and beta-carotene. Given this strain's impressive productivity when compared to
      commercial strains, such as Schizochytrium sp. SR21 (which has only 50% TFA),
      coupled with its ability to grow at economical nitrogen and very low salt
      concentrations (2 g L(-1)), ONC-T18 is seen as an ideal candidate for both scale
      up and commercialization.

PMID- 16625395
TI  - Alternatively spliced Robo2 isoforms in zebrafish and rat.
AB  - Robo2, a member of the robo gene family, functions as a repulsive axon guidance
      receptor as well as a regulator of cell migration and tissue morphogenesis in
      different taxa. In this study, a novel isoform of the zebrafish robo2
      (robo2_tv2), which included an otherwise alternatively spliced exon (CAE), has
      been characterized. Robo2_tv2 is expressed differentially in most non-neuronal
      tissues of adult zebrafish whereas robo2_tv1 expression to a great extent is
      restricted to the brain and eye. In zebrafish, robo2_tv2 exhibits a very-low
      level basal expression starting from 1 day post fertilization until the mid
      larval stages, at which time its expression increases dramatically and could be
      detected throughout adulthood. Our findings demonstrate that the amino acid
      sequence coded by CAE of the robo2 gene is highly conserved between zebrafish and
      mammals, and also contains conserved motifs shared with robo1 and robo4 but not
      with robo3. Furthermore, we provide an account of differential transcription of
      the CAE homolog in various tissues of the adult rat. These results suggest that
      the alternatively spliced robo2 isoforms may exhibit tissue specificity.

PMID- 16625396
TI  - No effect of pulsed electromagnetic fields on PC12 and HL-60 cells.
AB  - The effect of pulsed electromagnetic fields (PEMF) similar to those used in
      transcranial magnetic stimulation (TMS) on two tumour cell lines, the human
      promyelocytic leukaemia cell line (HL-60) and the rat pheochromocytoma cell line
      (PC12), was investigated. The two cell lines were exposed to non-homogeneous
      pulsed electromagnetic fields (about 0.25-4.5 T peak magnetic field strength; 1-8
      exponential pulses, 0.25 Hz) at different positions on the coil (2x25 mm). After
      exposure with various intensities, various numbers of pulses and at different
      coil positions, cell viability and the intracellular cyclic AMP content were
      determined in the two cell lines. Additionally, in HL-60 cells the intracellular
      Hsp72 content and in PC12 cells the release of the neurotransmitters dopamine,
      noradrenaline and acetylcholine were measured after PEMF treatment. The results
      of these analyses do not hint at alterations in the cell viability or in the
      content of cAMP, Hsp72, dopamine, noradrenaline, and acetylcholine in the two
      tumour cell lines after PEMF exposure under various conditions.

PMID- 16625397
TI  - SEUSS and LEUNIG regulate cell proliferation, vascular development and organ
      polarity in Arabidopsis petals.
AB  - Unlike in animals where cell migrations and programmed cell death play key roles
      in organ shape determination, in plants organ shape is largely a result of
      coordinated cellular growth (cell divisions and cell elongations). We have
      investigated the role of the SEUSS and LEUNIG genes in Arabidopsis thaliana (L.)
      Heynh. petal development to better understand the molecular mechanisms through
      which cellular growth and organ shape are coordinated in plants. SEUSS and LEUNIG
      encode components of a putative transcriptional regulatory complex that controls
      organ identity specification through the repression of the floral organ identity
      gene AGAMOUS. SEUSS and LEUNIG also regulate petal shape through AGAMOUS
      independent mechanisms; however, the molecular and cellular actions of SEUSS and
      LEUNIG during petal development are unknown. Here we show that SEUSS and LEUNIG
      control blade cell number and vasculature development within the petal.
      Furthermore, SEUSS and LEUNIG regulate petal polarity along the adaxial/abaxial
      axis. We present a model where SEUSS and LEUNIG are required to potentiate the
      key polarity genes PHABULOSA and FILAMENTOUS FLOWER/YABBY1 and thus influence
      cellular growth within the developing petal blade.

PMID- 16625398
TI  - A rare case of nasopharyngeal angiofibroma in an elderly female.
AB  - Nasopharyngeal angiofibromas occur predominantly in males in their puberty and
      adolescence; the incidence in other age groups and in women is exceptional. This
      report describes a case of a 57-year-old woman with nasopharyngeal angiofibroma
      presenting typical radiological findings in computed tomography, MR imaging and
      angiography. The tumour was successfully removed and histopathological
      examination confirmed the diagnosis. In 6 years follow-up the patient is free of
      symptoms.

PMID- 16625399
TI  - Saccular damage in patients with high-frequency sensorineural hearing loss.
AB  - Subjects with high frequency sensorineural hearing loss (HF-SNHL) without
      retrocochlear pathology are those group which certainly encountered inner ear
      damaging factors. This study was designed to evaluate the effects of cochlear
      damaging factors on the sacculocollic pathway. Fifty patients (76 ears) with
      varying degrees of HF-SNHL but without clinical manifestations of vestibular
      pathology tested for vestibular evoked myogenic potentials (VEMP). The results
      were compared with those of 18-healthy referents (32 ears) examined in the same
      way. Subjects with HF-SNHL greater than 40 dB HL showed significantly more
      saccular deterioration, estimated as negative VEMP responses than did the
      referents. This suggests subclinical disturbances of the vestibular system
      especially of the saccule in these patients. The underlying mechanism may be
      simultaneous damage to both the cochlea and saccule by the same factors.

PMID- 16625400
TI  - First branchial cleft fistula presenting with external opening on earlobe.
AB  - First branchial cleft fistula is a rare congenital malformation of the head and
      neck with an incidence of less than 10% of all branchial cleft defects. We herein
      report a 15-year-old girl who had a cystic mass in the postauricular region with
      an external opening on the posterior face of the earlobe. Surgical exploration
      revealed that a second sinus tract was passing through the conchal cartilage
      without going beyond the skin of the external acoustic meatus. The mass and the
      tract were excised along with the opening on the earlobe as well as the skin
      island surrounding the opening. The case was treated surgically with success .
      The significance of our case was the location of external opening on the earlobe.

PMID- 16625406
TI  - Acute traumatic renal artery to inferior vena cava fistula treated with a covered
      stent.
AB  - A 34-year-old man presented within hours of suffering a penetrating stab wound
      and was diagnosed with a right renal artery to inferior vena cava fistula.
      Initial attempts at excluding the fistula with a balloon were unsuccessful. He
      was subsequently treated with a covered stent inserted into the right renal
      artery which successfully excluded the fistula.

PMID- 16625409
TI  - Endovascular embolization of visceral artery aneurysms with ethylene-vinyl
      alcohol (Onyx): a case series.
AB  - We report the application of the liquid embolic agent ethylene-vinyl alcohol
      (Onyx; MicroTherapeutics, Irvine, CA, USA) in the management of visceral artery
      aneurysms. The technique and indications for using Onyx are discussed with
      emphasis on the management of wide-necked aneurysms and maintenance of patency of
      the parent vessel. None of the cases was considered suitable for stent-grafting
      or embolization with conventional agents. Two aneurysms of the renal artery
      bifurcation and one aneurysm of the inferior pancreaticoduodenal artery were
      treated. Following treatment there was complete exclusion of all aneurysms. There
      was no evidence of end-organ infarction. Follow-up with intervals up to 6 months
      has shown sustained aneurysm exclusion. Onyx is known to be effective in the
      management of intracranial aneurysms. Our experience demonstrates the efficacy
      and applicability of the use of Onyx in the treatment of complex visceral artery
      aneurysms.

PMID- 16625410
TI  - Routine use of three-dimensional contrast-enhanced moving-table MR angiography in
      patients with peripheral arterial occlusive disease: comparison with selective
      digital subtraction angiography.
AB  - PURPOSE: To compare the diagnostic accuracy of contrast-enhanced (CE) three
      dimensional (3D) moving-table magnetic resonance (MR) angiography with that of
      selective digital subtraction angiography (DSA) for routine clinical
      investigation in patients with peripheral arterial occlusive disease. METHODS:
      Thirty-eight patients underwent CE 3D moving-table MR angiography of the pelvic
      and peripheral arteries. A commercially available large-field-of-view adapter and
      a dedicated peripheral vascular phased-array coil were used. MR angiograms were
      evaluated for grade of arterial stenosis, diagnostic quality, and presence of
      artifacts. MR imaging results for each patient were compared with those of
      selective DSA. RESULTS: Two hundred and twenty-six arterial segments in 38
      patients were evaluated by both selective DSA and MR angiography. No
      complications related to MR angiography were observed. There was agreement in
      stenosis classification in 204 (90.3%) segments; MR angiography overgraded 16
      (7%) segments and undergraded 6 (2.7%) segments. Compared with selective DSA, MR
      angiography provided high sensitivity and specificity and excellent interobserver
      agreement for detection of severe stenosis (97% and 95%, kappa = 0.9 +/- 0.03)
      and moderate stenosis (96.5% and 94.3%, kappa = 0.9 +/- 0.03). CONCLUSION:
      Compared with selective DSA, moving-table MR angiography proved to be an
      accurate, noninvasive method for evaluation of peripheral arterial occlusive
      disease and may thus serve as an alternative to DSA in clinical routine.

PMID- 16625412
TI  - Hand and wrist arterial aneurysms.
AB  - Hand and wrist aneurysms are a rare pathology, but recently the number of cases
      is increasing because of iatrogenic injuries such as catheter placement for
      endovascular procedures, invasive blood pressure monitoring, and arterial blood
      collection. In the period between January 1992 and January 2005, seven patients
      were treated at our institution for hand and wrist aneurysms. Five were true
      aneurysms and two were false aneurysms. All patients underwent surgery: four had
      aneurysmectomy and ligation of the arterial stumps and three had lesion removal,
      with arterial break suture in two cases and reconstruction with interposition of
      reversed autologous vein in the other case. In all cases, we did not have any
      postoperative ischemic or neurological complications. Symptoms like pain,
      paresthesia, and disesthesia combined with the minimal morbidity associated with
      repair suggest that operative repair of these aneurysms should be routinely
      performed.

PMID- 16625413
TI  - Primary aortoduodenal fistula without abdominal aortic aneurysm in association
      with psoas abscess.
AB  - Primary aortoenteric fistula (PAEF) is a communication between the aorta and the
      enteric tract without any previous vascular intervention, e.g., aortic grafting.
      Although rare, PAEF is a potentially lethal condition that requires a high index
      of suspicion and prompt surgical intervention. Most of the reported cases involve
      an abdominal aortic aneurysm. However, in this report, we describe a rare case of
      a primary aortoduodenal fistula in a nonaneurysmal aorta in association with a
      psoas abscess, which was treated successfully. At 2-year follow-up, the patient
      is alive without episodes of bleeding or fever.

PMID- 16625414
TI  - Superficial femoral vein and superficial femoral artery as replacement for
      infected axillofemoral graft.
AB  - We report successful replacement of infected axillofemoral bypass with a combined
      femoral vein and superficial femoral artery graft. The new graft was transferred
      through the tunnel left after infected prosthesis removal. Good early and long
      term results indicate that this may be a sufficient procedure.

PMID- 16625415
TI  - Percutaneous mesenteric stenting followed by laparoscopic exploration for
      visceral malperfusion in acute type B aortic dissection.
AB  - A 55-year-old man underwent percutaneous mesenteric and left renal stenting for
      malperfusion in acute type B aortic dissection. Laparoscopic exploration was
      performed immediately after percutaneous revascularization to ensure the
      integrity of the abdominal viscera. Because the diagnosis of mesenteric
      infarction may sometimes be difficult and its delay can be fatal, we advocate
      laparoscopic exploration as a mini-invasive method after percutaneous management
      of visceral malperfusion, if the integrity of the abdominal viscera needs to be
      verified.

PMID- 16625416
TI  - Right aortic arch with aberrant left subclavian artery symptomatic in adulthood.
AB  - Congenital malformations of the aortic arch are rarely found in adulthood. We
      describe three cases of right aortic arch with aberrant left subclavian artery
      with left-sided ligamentum arteriosum presenting in adulthood as vascular rings
      with symptoms of tracheal compression. Varying presentation as well as surgical
      strategy which was individualized according to the pathological anatomy of each
      case are discussed.

PMID- 16625417
TI  - Endovascular repair of a thoracoabdominal aortic aneurysm involving the celiac
      artery and the superior mesenteric artery.
AB  - We present a successful endovascular repair of a thoracoabdominal aortic aneurysm
      (TAAA) involving the celiac artery and the superior mesenteric artery. After the
      intentional occlusion of the celiac artery, an Inoue stent graft with a side arm
      to the superior mesenteric artery was implanted. Management of the visceral
      arteries in the endovascular repair of TAAA was highlighted.

PMID- 16625418
TI  - Superior vena cava bypass with superficial femoral vein for benign superior vena
      cava syndrome.
AB  - Superior vena cava (SVC) syndrome can result from benign causes such as temporary
      hemodialysis catheters placed into the central veins. The indications for open,
      surgical revascularization are rare and usually reserved for patients whose
      symptoms are refractory to anticoagulation and endovascular treatment. The
      current report documents the case of a 54-year-old woman with recurrent SVC
      syndrome secondary to long-term indwelling central venous catheters for total
      parenteral nutrition. She presented to the vascular service with moderate
      head/neck edema and persistent headaches despite chronic anticoagulation and
      multiple previous endovascular attempts including both angioplasty and stenting.
      An internal jugular-SVC bypass was performed using autogenous superficial femoral
      vein (SFV), which resulted in the resolution of her symptoms and a patent graft
      12 months postoperatively. Autogenous SFV is an ideal conduit for central vein
      revascularization secondary to its size, relative ease associated with
      harvesting, and handling characteristics. It may be the ideal conduit for
      revascularization in patients with SVC syndrome secondary to benign causes
      because of their favorable life expectancy, although documentation of long-term
      graft patency is necessary.

PMID- 16625420
TI  - Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen
      species generation and plasminogen activator inhibitor-1 induction.
AB  - Heme oxygenase-1 (HO-1) responds to a variety of oxidative stresses. We examined
      whether HO-1 expression influences pro-thrombotic processes, in which the
      involvement of oxidative stress has been reported. Since HO-1 knockout mice with
      a C57/BL6J background were not viable, embryonic cells from HO-1 deficient mice
      (E11.5) were used. Cell viability, the level of plasminogen activator inhibitor-1
      (PAI-1) expression and reactive oxygen species (ROS) generation of HO-1 deficient
      cells in response to the exposures to hydrogen peroxide and oxidized LDL were
      compared to those with wild-type cells. We also examined the effects of
      glutathione (GSH), desferrioxamine (DFO) and diphenyleneiodonium (DPI: an NADPH
      oxidase inhibitor) as well as of the HO reaction products, bilirubin (BR) and
      carbon monoxide (CO) on PAI-1 expression and ROS generation. PAI-1 expression and
      ROS generation were markedly elevated in HO-1 deficient cells compared to wild
      type cells. Exposure to oxidized LDL significantly elevated PAI-1 expression and
      ROS production in HO-1 deficient cells. Interestingly, these increases in HO-1
      deficient cells were significantly lowered by BR, CO, GSH and DPI while DFO had
      little effect. Furthermore, BR and CO were effective to improve viabilities of HO
      1 deficient cells. These results suggest that HO-1 may be required to suppress
      ROS generation and the production of pro-thrombotic molecules such as PAI-1.

PMID- 16625421
TI  - Differential involvement of mitochondrial permeability transition in cytotoxicity
      of 1-methyl-4-phenylpyridinium and 6-hydroxydopamine.
AB  - Defects in mitochondrial function have been shown to participate in the induction
      of neuronal cell injury. The aim of the present study was to assess the influence
      of the mitochondrial membrane permeability transition inhibition against the
      toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) and 6-hydroxydopamine (6-OHDA)
      in relation to the mitochondria-mediated cell death process and role of oxidative
      stress. Both MPP(+) and 6-OHDA induced the nuclear damage, the changes in the
      mitochondrial membrane permeability, leading to the cytochrome c release and
      caspase-3 activation, the formation of reactive oxygen species and the depletion
      of GSH in differentiated PC12 cells. Cyclosporin A (CsA), trifluoperazine and
      aristolochic acid, inhibitors of mitochondrial permeability transition,
      significantly attenuated the MPP(+)-induced mitochondrial damage leading to
      caspase-3 activation, increased oxidative stress and cell death. In contrast to
      MPP(+), the cytotoxicity of 6-OHDA was not reduced by the addition of the
      mitochondrial permeability transition inhibitors. The results show that the
      cytotoxicity of MPP(+) may be mediated by the mitochondrial permeability
      transition formation, which is associated with formation of reactive oxygen
      species and the depletion of GSH. In contrast, the 6-OHDA-induced cell injury
      appears to be mediated by increased oxidative stress without intervention of the
      mitochondrial membrane permeability transition.

PMID- 16625422
TI  - Insight into the role of DL-alpha-lipoic acid against cyclophosphamide induced
      alterations in calcium sensitivity of cardiac myofilaments.
AB  - Cyclophosphamide (CP), a potent antitumor drug, is known to cause severe
      cardiotoxicity. The present study is aimed at evaluating the role of DL-alpha
      Lipoic acid (LA) on the calcium responsiveness of cardiac myofilaments isolated
      from CP treated rats. Adult male Wistar rats were divided into four treatment
      groups. Two groups received single intraperitoneal injection of CP (200 mg/kg
      b.wt.) to induce cardiotoxicity, one of these groups received LA treatment (25
      mg/kg b.wt. for 10 days). A vehicle treated control group and a LA drug control
      were also included. Cardiotoxicity was evident from increased levels of cardiac
      Troponin I in serum of CP treated rats. The pCa-actomyosin ATPase relationship of
      myofilaments demonstrated a rightward shift indicating diminished responsiveness
      in CP treated rats. The hill coefficient was reduced and the myofibrillar myosin
      Ca(2+)-ATPase and K(+)-(EDTA) activities were also significantly (P < 0.05)
      reduced. Ultrastructural observations were also in agreement with the above
      abnormal changes, wherein loss of myofilaments occurred. LA effectively
      normalized these abnormalities and restored the cardiac function in CP
      administered rats.

PMID- 16625424
TI  - Native Thai speakers' acquisition of English word stress patterns.
AB  - The influence of syllabic structure, lexical class and stress patterns of known
      words on the acquisition of the English stress system was investigated in ten
      native Thai speakers. All participants were adult learners of English with an
      average length of residence in the US of 1.4 years. They were asked to produce
      and give perceptual judgments on 40 English non-words of varying syllabic
      structures in noun and verb sentence frames. Results of the production data
      suggested that syllables with a long vowel attracted stress more often than
      syllables containing a short vowel and nouns received initial stress more often
      than verbs. Additionally, regression analyses with the three factors as
      predictors suggested that Thai participants' pattern of stress assignment on non
      words was significantly influenced by the stress patterns of phonologically
      similar real words. These results were compared and contrasted to those found in
      previous work with Spanish-English and Korean-English bilinguals.

PMID- 16625419
TI  - Development of expressed sequence tags from the bay scallop, Argopecten irradians
      irradians.
AB  - The bay scallop, Argopecten irradians irradians, introduced from North America,
      has become one of the most important aquaculture species in China. Inan effort to
      identify scallop genes involved in host defense, a high-quality cDNA library was
      constructed from whole body tissues of the bay scallop. A total of 5828
      successful sequencing reactions yielded 4995 expressed sequence tags (ESTs)
      longer than 100 bp. Cluster and assembly analyses of the ESTs identified 637
      contigs (consisting of 2853 sequences) and 2142 singletons, totaling 2779 unique
      sequences. Basic Local Alignment Search Tool (BLAST) analysis showed that the
      majority (73%) of the unique sequences had no significant homology (E-value </=
      0.005) to sequences in GenBank. Among the 748 sequences with significant GenBank
      matches, 160 (21.4%) were for genes related to metabolism, 131 (17.5%) for
      cell/organism defense, 124 (16.6%) for gene/protein expression, 83 (11.1%) for
      cell structure/motility, 70 (9.4%) for cell signaling/communication, 17 (2.3%)
      for cell division, and 163 (21.8%) matched to genes of unknown functions. The
      list of host-defense genes included many genes with known and important roles in
      innate defense such as lectins, defensins, proteases, protease inhibitors, heat
      shock proteins, antioxidants, and Toll-like receptors. The study provides a
      significant number of ESTs for gene discovery and candidate genes for studying
      host defense in scallops and other molluscs.

PMID- 16625427
TI  - Disease progression and pharmacodynamics in Parkinson disease - evidence for
      functional protection with levodopa and other treatments.
AB  - We have modelled the Unified Parkinson's Disease Rating Scale (UPDRS) scores
      collected in 800 subjects followed for 8 years. Newly diagnosed and previously
      untreated subjects were initially randomized to treatment with placebo, deprenyl,
      tocopherol or both and, when clinical disability required, received one or more
      dopaminergic agents (levodopa (carbidopa/levodopa), bromocriptine, or pergolide).
      Using models for disease progression and pharmacodynamic models for drug effects
      we have characterized the changes in UPDRS over time to determine the influence
      of the various drug treatments. We have confirmed and quantitated the relative
      symptomatic benefits of the dopaminergic agents and provide model-based evidence
      for slowing of disease progression.

PMID- 16625428
TI  - Analysis of the late steps of exocytosis: biochemical and total internal
      reflection fluorescence microscopy (TIRFM) studies.
AB  - 1. Time with Julie in his laboratory at the NIH in the early 1970s is remembered.
      The experience led to a life-long interest in the regulation of catecholamine
      secretion. Here are summarized aspects of this work. 2. The relationship between
      ATP-dependent priming of exocytosis and the polyphosphoinositides is reviewed. In
      addition, studies are summarized in which total internal reflection fluorescent
      microscopy (TIRFM) was used to visualize secretory granule behavior before
      exocytosis and individual exocytotic events. 3. Quantitative optical analysis
      indicates that chromaffin granule motion is highly restricted but regulated.
      Granules can undergo significant motion in the 100 ms prior to fusion and
      interactions with the plasma membrane leading to fusion can occur within this
      time. The small motions may permit granules adjacent to the plasma membrane to
      repetitively sample microdomains of the plasma membrane, thereby increasing the
      probability of fruitful interactions that lead to fusion.

PMID- 16625431
TI  - Rostrocaudal somatotopy in the neural connections between the lateral
      hypothalamus and the dorsal periaqueductal gray of the rat brain.
AB  - 1. The lateral hypothalamus (LH) and the dorsal periaqueductal gray area (dPAG)
      are two important brain structures involved in central cardiovascular control. 2.
      In the present study, we searched for possible rostrocaudal somatotopy in the
      neural connections from the three subdivisions of the LH (anterior-LHa; tuberal
      LHt and posterior-LHp) to the different rostrocaudal portions of the dPAG. 3. The
      bidirectional neuronal tracer biotinylated-dextran-amine (BDA) was microinjected
      into different rostrocaudal coordinates of the dPAG (AP 3.4-2.7 mm) of male
      Wistar rats. One week later, animals were sacrificed and brain slices were
      processed and analyzed to detect neuronal efferent projections from the LH to the
      dPAG. 4. Neuronal cell body staining was observed along all the rostrocaudal axis
      of the LH when BDA was microinjected in more rostral dPAG coordinates. When the
      BDA was microinjected into more caudal dPAG regions, labeled neurons were
      observed only in the caudal portion of the LH. 5. Efferent projections from the
      LHa were directed only to the rostral portion of the dPAG. Projections from the
      rostral and medial portions of the LHt were also directed to the rostral dPAG,
      whereas both rostral and caudal dPAG received projections from the caudal portion
      of the LHt. Efferent projections from the anterior portion of the LHp were
      directed to both rostral and caudal dPAG, whereas projections from the caudal LHp
      were only directed to the rostral portion of the dPAG.6. The results suggest a
      somatotopic correlation in LH projections to the dPAG with main connections to
      the rostral dPAG, which are efferent from the three divisions of the LH. More
      caudal regions of the dPAG received afferents only from posterior sites in the
      LH. 7. Moreover, the results point out to extensive and complex neural
      somatotopic projections from all LH subdivisions to different rostrocaudal
      portions of the dPAG, reinforcing the idea of significant functional interactions
      between the brain structures.

PMID- 16625432
TI  - The effect of swelling on TRH and oxytocin secretion from hypothalamic
      structures.
AB  - 1. Cell swelling induces exocytosis of material stored in secretory vesicles
      resulting in a secretory burst of peptidic hormones or enzymes from various types
      of cells including endocrine cells and neurons. We have previously shown that
      swelling-induced exocytosis possesses limited selectivity; hypotonic medium
      evokes TRH but not oxytocin release from hypothalamic paraventricular nucleus
      (PVN) and neurohypophysis (NH). 2. It is the aim of this study to ascertain
      whether the swelling-induced oxytocin secretion could be unmasked by the
      inhibition of specific osmotic response using Ca(2+)-free medium and GdCl(3), an
      inhibitor of stretch activated channels. 3. Oxytocin release from the PVN was
      stimulated by the hypotonic medium only in the presence of 50 or 100 microM
      GdCl(3.) Oxytocin release from supraoptic nucleus (SON) was also stimulated by
      the Ca(2+)-free hypotonic medium in the presence of GdCl(3). Oxytocin secretion
      from the NH was not stimulated even in the presence of GdCl(3), both in Ca(2+)
      containing and Ca(2+)-free medium. TRH response to swelling-inducing stimulus was
      not affected by the presence of GdCl(3). 4. An intranuclear oxytocin secretion to
      hyposmotic stimulation within the PVN and the SON could be unmasked by the
      inhibiting specific response by GdCl(3). At these conditions general secretory
      response to swelling-inducing stimuli emerged. Secretion of oxytocin from the NH
      was not affected by any of these treatments. 5. Peptides and proteins released
      after cell swelling can play an important role in the pathophysiology of ischemia
      and could be mediators of local or remote preconditioning. Disruption of
      mechanosensitive gating in magnocellular neurosecretory cells could result in an
      inadequate secretory response (e.g. stimulation instead of inhibition and vice
      versa) of hormones engaged in water and salt metabolism regulation.

PMID- 16625433
TI  - The plasticity of the DRG neurons belonging to different subpopulations after
      dorsal rhizotomy.
AB  - 1. The plasticity of sensory neurons following the injury to their axons is very
      important for prognosis of recovery of afferent fibers with different modality.
      It is evident that the response of dorsal root ganglion (DRG) neurons after
      peripheral axotomy is different depending on the deficiency in neurotrophic
      factors from peripheral region. The loss of cells appears earlier and is more
      severe in B-cells (small, dark cells with unmyelinated axons) than in A-cells
      (large, light cells with myelinated axons). 2. We studied using
      immunohistochemical methods the response of DRG neurons to dorsal rhizotomy and
      combined injury of central and peripheral neuronal processes. A quantitative
      analysis of DRG neurons tagged by the selective markers isolectin B4 (IB4) and
      the heavy molecular component of the neurofilament triplet (NF200) antibody,
      selective for subpopulations of small and large/medium DRG neurons, respectively,
      was performed after dorsal rhizotomy, peripheral axotomy, and their combination.
      3. The number of NF200(+)-neurons is reduced substantially after both dorsal
      rhizotomy and peripheral axotomy, while the decrease of IB4(+)-neurons is
      observed only in combined injury, i.e., dorsal rhizotomy accompanied with sciatic
      nerve injury. 4. Our results show that distinct subpopulations of DRG neurons
      respond differently to the injury of their central processes. The number of
      NF200(+)-neurons decreases to greater degree following dorsal rhizotomy in
      comparison to IB4(+)-neurons.

PMID- 16625438
TI  - Corpus callosum morphometrics in young children with autism spectrum disorder.
AB  - This study assessed midsagittal corpus callosum cross sectional areas in 3-4 year
      olds with autism spectrum disorder (ASD) compared to typically developing (TD)
      and developmentally delayed (DD) children. Though not different in absolute size
      compared to TD, ASD callosums were disproportionately small adjusted for
      increased ASD cerebral volume. ASD clinical subgroup analysis revealed greater
      proportional callosum reduction in the more severely affected autistic disorder
      (AD) than in pervasive developmental disorder-not otherwise specified (PDD-NOS)
      children. DD children had smaller absolute callosums than ASD and TD. Subregion
      analysis revealed widely distributed callosum differences between ASD and TD
      children. Results could reflect decreased inter-hemispheric connectivity or
      cerebral enlargement due to increase in tissues less represented in the corpus
      callosum in ASD.

PMID- 16625441
TI  - [The post-polio syndrome].

PMID- 16625442
TI  - [The modified Ludloff osteotomy for correction of severe metatarsus primus varus
      with hallux valgus deformity].
AB  - AIM: The present study investigates the clinical and radiological mid-term
      results of the modified Ludloff osteotomy, a proximal metatarsal osteotomy for
      surgical correction of severe metatarsus primus varus with hallux valgus
      deformity. METHOD: 70 feet in 67 patients from 25 to 78 years (average age 56
      years) were included in this prospective study. The patients were evaluated with
      the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot
      metatarsophalangeal interphalangeal score, which was used preoperatively and at
      an average follow-up of 37 +/- 6 months. Weight-bearing foot radiographs were
      analysed according to AOFAS guidelines and statistical evaluation was made with
      the Wilcoxon signed-rank test. RESULTS: The average AOFAS score improved
      significantly (p < 0.0001) from 55.2 +/- 15.2 points preoperatively to 86.6 +/-
      15.2 points at follow-up. Preoperatively, all patients complained of pain (20.2
      +/- 9.6 points) which had improved significantly (p < 0.0001) at the latest
      follow-up (37.3 +/- 5.7 points). The average hallux valgus angle (HVA) was 37 +/-
      8 degrees preoperatively and improved significantly to 12 +/- 11 degrees at
      follow-up (p = 0.0001). The intermetatarsal angle (IMA) improved significantly
      from 18 +/- 2 degrees preoperatively to 8 degrees +/- 4 degrees after 37 +/- 6
      months (p = 0.0002). The sesamoid position improved significantly from
      preoperative to follow-up (p = 0.0003). Radiographic evaluation of the patients
      indicated that all examined osteotomies had healed after 37 +/- 6 months.
      CONCLUSION: This prospective investigation at intermediate follow-up using
      currently available outcome measures suggests that the Ludloff osteotomy is a
      suitable procedure for the surgical correction of severe metatarsus primus varus
      (IMA > 15 degrees ) with hallux valgus deformity.

PMID- 16625443
TI  - [Ambulation training with bilateral limited weight bearing after foot injuries].
AB  - AIM: Bilateral foot injuries are not uncommon. Operative treatment usually
      requires partial weight bearing over several weeks. This is a challenge for
      physiotherapy especially for ambulation training. We describe a new
      rehabilitation aid allowing for bilateral limited weight bearing during
      ambulation. METHODS: Ambulation training was initiated in the early postoperative
      period using the Regensburg ambulation aid. A lift system allows for exact
      limitation of weight bearing on both sides controlled by balances integrated into
      the floor. Using a rail system a 15 m free walking distance is available. This
      study included 10 patients with bilateral foot fractures. The functional outcome
      was assessed using the AOFAS score and quality of life with the SF-36 score.
      Plain X-rays were used to evaluate loss of correction. The control group
      consisted of 20 patients where ambulation training was discontinued for at least
      6 weeks postoperatively. RESULTS: The system is very safe, during the entire
      period no complication was recorded. Acceptance among the patients was extremely
      high. Worries about unwanted weight bearing could be reduced. Patients mobilized
      with early ambulation training showed a better compensation of gait if compared
      to the control group. Secondary problems in the knee, hip or spine, as well as
      muscular deficiencies had a significantly lower incidence. No loss of correction
      could be seen in either of the two groups. CONCLUSION: The presented ambulation
      aid is a significant contribution to the physiotherapy of bilateral foot
      injuries.

PMID- 16625445
TI  - [Sensorimotor potential of the intact and injured anterior and posterior cruciate
      ligaments--a neurophysiological study in an animal model].
AB  - AIM: This neurophysiological study is intended to investigate the sensomotor
      potential of the anterior cruciate ligament (ACL) and the posterior cruciate
      ligament (PCL) which may provide joint stabilization via a ligamentomuscular
      reflex arch. In addition, the role of ligamentous injury on the sensomotor
      potential has been investigated. METHOD: The sensomotor potential was
      investigated using 24 knee joints in a sheep model under in-vivo conditions. The
      cruciate ligaments were mechanically loaded and the muscular activities of the
      hamstrings and the quadriceps were recorded simultaneously via electromyography.
      Injury to the ligaments was simulated by defined mechanical elongation of the ACL
      and PCL to failure. RESULTS: The results confirm the hypothesis of the existence
      of a ligamentomuscular reflex loop between ligamentary mechanoreceptors and the
      joint-stabilizing muscles. Mechanical loading of the ACL triggered mainly the
      activity of the hamstrings, whereas loading of the PCL led to the activation of
      the quadriceps. The rate of elongation which caused disturbances to the
      sensomotor potential was significantly smaller as compared to the elongation to
      failure. CONCLUSION: The cruciate ligaments provide dynamic joint stabilization
      via a ligamentomuscular reflex arch. It was demonstrated that the sensomotor
      potential of both structures is significantly more susceptible to ligament injury
      than the biomechanical potential.

PMID- 16625444
TI  - [Influence of postoperative shoes on plantar pressure patterns].
AB  - AIM: There are several different types of shoe devices in the postoperative
      treatment of forefoot surgery. They all have the aim to unload the operated
      region. Examples for forefoot surgery are hallux valgus operations or correction
      of claw toes. The aim of this study was to compare a special forefoot shoe
      (Darco's Ortho Wedge) with a lengthwise and crosswise prepared postoperative shoe
      (Darco's Medical Surgical). METHOD: Plantar pressure distribution measurements
      were used to evaluate the unloading effect of the shoe conditions. The pressure
      in a standard shoe (Nike's Air Triax) was measured for further comparison.
      RESULTS: The results demonstrate that all analyzed shoes relieve weight under the
      medial forefoot region. The lengthwise prepared Medical Surgical achieves the
      highest pressure reduction under the medial forefoot, but the midfoot and the
      lateral forefoot are subjected to significantly higher loads. The Ortho Wedge
      reduces the load under the toes and the forefoot and relieves the midfoot region.
      The pressure is redistributed under the hindfoot. The crosswise prepared Medical
      Surgical also relieves pressure under the forefoot but not to the same extent as
      the Ortho Wedge. CONCLUSION: In conclusion it can be stated that the Ortho Wedge
      shows the best results of the tested shoes for pressure relief and load transfer
      under the forefoot.

PMID- 16625446
TI  - [In vitro investigation of posterior cruciate ligament strain following total
      knee arthroplasty].
AB  - AIM: The aim of this biomechanical in vitro study was to assess posterior
      cruciate ligament (PCL) strain following two different total knee arthroplasty
      (TKA) designs (fixed versus mobile) with regard to modification of the tibial
      slope. MATERIAL AND METHODS: We investigated eight Natural Knee I (NK I)
      prosthesis with fixed bearing and eight Low Contact Stress (LCS) prosthesis with
      mobile meniscal bearings. TKA was performed using fresh frozen human cadaveric
      knee joints. PCL strain was measured with implantable force transducers. Knee
      kinematic assessment was made with a load of 300 Newton and without load using a
      six-degrees-of-freedom testing device. Modification of the tibial slope was
      analysed radiographically. Statistical analysis was performed using Student's t
      test, Wilcoxon rank sum test, and the Spearman coefficient of correlation.
      RESULTS: Assessment of the tibial slope showed a non-significant increase of 2.1
      degrees (p = 0.14) following TKA using the NK I, and of 1.1 degrees (p = 0.12)
      using the LCS, respectively. Analysis of PCL strain following implantation of the
      NK I prosthesis revealed non-significant alterations both with (p = 0.74) and
      without load (p = 0.20). Concerning the LCS prosthesis, a significant decrease in
      PCL strain was seen with load (p = 0.01), whereas non-significant modifications
      were measured without load (p = 1.0). The modified tibial slope and modified PCL
      strain following LCS TKA showed no (with load: r (s) = 0.01) and modest
      correlation (without load: r (s) = - 0.43), respectively, whereas it was
      substantial following NK I TKA (with load: r (s) = 0.64, without load: r (s) =
      0.70). CONCLUSION: As the NK I prosthesis allows PCL tension to be close to
      normal as the knee flexes, it can be stated that regular PCL tension after TKA is
      restorable and, moreover, it can be hypothesised that the effected tension of the
      PCL mainly depends on the interaction between design of the implant
      (fixed/mobile) and the functional role of the PCL.

PMID- 16625447
TI  - [Characterisation of human meniscus cells].
AB  - AIM: The meniscus of the human knee joint has an important function for the shock
      absorption, stability and power transmission from the upper to the lower leg.
      After meniscus injury often a partial or complete resection is necessary. Only
      injuries in the outer third may heal spontaneously or upon primary suture due to
      the vascularisation in these segments. After partial or total meniscectomy
      osteoarthritis of the knee joint is common in a large number of patients. The
      goal of our investigations was to establish meniscus cell cultures and to
      characterise the fibrochondrocytes (meniscus cells) in vitro. METHODS: We
      examined the expression of different growth factors, cytokines and proteins in
      human menisci from surgical preparations using immunohistochemistry and RT-PCR
      analysis. RESULTS: Human meniscus cells express the collagens I , II, III, and
      VI, the matrix metalloproteinases-1, -2, -3, -8, and -13, BMP-2, and -4,
      TGFbeta1, VEGF, IGF-I, and -II, FGF-2, endostatin, iNOS, vimentin, TIMP-1, and 
      2, aggrecan, IL-1beta, IL-6, and IL-18. Staining with the monoclonal antibody
      AS.02 in all examined cells confirmed their mesenchymal origin. CONCLUSION: New
      strategies for the treatment of meniscus damage can be derived from these results
      and further advances for the tissue engineering of meniscus tissue can be
      obtained.

PMID- 16625448
TI  - [The effect of osteoprotegerin on tendon-bone healing after reconstruction of the
      anterior cruciate ligament: a histomorphological and radiographical study in the
      rabbit].
AB  - AIM: Improvement of the bony incorporation of a soft-tissue graft after ACL
      reconstruction by local administration of Osteoprotegerin between the bone and
      tendon graft. METHOD: Fifteen New Zealand White rabbits underwent unilateral
      anterior cruciate ligament (ACL) reconstruction using an autologous
      semitendinosis tendon graft. We compared the effect of three OPG doses (5 microg,
      50 microg, or 100 microg) at the tendon-bone interface to the controls (OPG
      carrier) and ACL reconstruction only. Specimens were analyzed at 3 weeks using
      radiology, histology and histomorphometry to investigate the effect of OPG on the
      bony incorporation of the tendon graft. RESULTS: Animals treated with OPG 100
      microg had a significant (p = 0.007) increase in newly-formed bone around the
      graft compared to the control group (0.16 +/- 0.01 mm(2); 0.06 +/- 0.02 mm(2)).
      No significant differences were found between the controls and the other groups
      (tendon graft only, OPG 5 microg, and 50 microg) (p > 0.05). Bone mineral
      density, measured in image-pixel brightness (IPB; reference range: 0-255), along
      the edge of the bone tunnel was greater in the OPG 100 microg group (169.5 +/-
      5.9 IPB) compared to the control group (150.3 +/- 4.3 IPB) but this was not
      statistically significant (p = 0.083). There was a significant decrease in the
      number of osteoclasts per high-power microscopic fields (HPF) lining the bone
      tunnel in the OPG 100 microg group compared to the control group (4.4 +/- 2.5
      cells/HPF; 6.4 +/- 1.8 cells/HPF) (p = 0.022). No significant differences were
      found between the control group and the other groups in osteoclast numbers (p >
      0.05). CONCLUSION: Since tendon-bone healing requires new bone formation and bone
      ingrowth around a tendon graft, OPG may improve biologic graft fixation. A
      potential implication could be earlier return to function or better conditions in
      revision surgery.

PMID- 16625449
TI  - [Effects of bisphosphonates in arthroplasty].
AB  - AIM: This study presents an overview of the general effects of bisphosphonates
      and in particular of their effects on different problems in joint arthroplasty.
      METHOD: First the chemical properties are described, then the biological effects.
      It is already known that bisphosphonates have effects on orthopaedic diseases and
      an increasing number of studies are investigating what effects can be achieved in
      joint arthroplasty with these substances. RESULTS: The bisphosphonates group was
      derived from industrial pyrophosphate which is used to prevent calcification.
      Bisphosphonates inhibit bone mineralisation and resorption. Several direct and
      indirect mechanisms are responsible for these effects. The inhibition of bone
      resorption is used to benefit patients suffering from various diseases causing
      increased bone resorption. Treatment with bisphosphonates results in greater bone
      density and improved mechanical bone quality. Indications for this treatment
      include osteoporosis, tumour-associated osseo-destruction, fibrous dysplasia and
      Paget's disease. Recent studies have shown that osseo-integration of metal
      implants is accelerated and periprosthetic bone loss, which is caused by various
      different mechanisms during the lifetime of an implant, can be reduced.
      CONCLUSION: Bisphosphonates have been an established element in the treatment of
      bone metabolic disorders for many years. Their use in joint arthroplasty could
      become increasingly important.

PMID- 16625450
TI  - [Long-term influence of the spongiosa metal surface prosthesis on the
      periprosthetic bone. A radiological and osteodensitometric analysis of
      implantation of the S& G (ESKA) hip prosthesis].
AB  - INTRODUCTION: The anatomically shaped, cementless total hip replacement (THR) (S
      and G, ESKA Lubeck) has a fully porous coating for secondary osseointegration.
      The aim of the present study was to analyse the long-term effect of the
      prosthesis on periprosthetic bone remodelling. METHODS: 137 THR in 117 patients
      were analysed clinically and radiographically 12.8 years (10-14.9 years)
      postoperatively. The average age at the last follow-up was 71.8 years (range: 34
      87 years). Osteodensitometric DEXA measurements of the periprosthetic bone in
      comparison to the contralateral non-operated femora were performed. RESULTS:
      Cumulative survival rates of all implanted THR (n = 231) at 14.9 years were 86.2
      % (+/-5.3 %) for the fully porous coated stem and 90.1 % (+/- 8 %) for the cup.
      Five stem fractures (3.6 %) at the middle part were recorded. The Harris hip
      score of the non-revised THR at the last follow-up averaged 88.3 (34-100) points.
      Bony atrophy in the proximal periprosthetic femora in Gruen zones I (16.8 %) and
      VII (34.6 %) confirmed a proximal stress-shielding. Osteodensitometric analyses
      demonstrated in comparison to the contralateral femora (BMD 1.3 g/cm (2)) a
      significantly reduced bone density at the calcar femoris (BMD 0.9 g/cm (2)) (p <
      0.001). CONCLUSION: The original goal of a physiological load transfer has not
      been realised with this fully porous, cementless THR. The anatomic S & G stem
      will mainly be osseointegrated by distal load transfer.

PMID- 16625451
TI  - [Limited, haemoglobin-dependent indication for autologous blood donation in total
      hip or knee replacement].
AB  - AIM: The rejection rate of autologous blood donation before joint replacement is
      high. The influence of the haemoglobin value and the age of patient before
      autologous blood donation was examined according to the necessity for blood
      transfusion. METHOD: In a retrospective study, the data of 233 patients who had
      donated autologous blood before hip (THR) or knee arthroplasty (TKR) were
      analysed. RESULTS: 72 patients (30.9 %) received an autologous blood transfusion
      during surgery or in the further course until the first day after surgery. A
      multivariate analysis showed no significant influence of age on the need for
      transfusions (p = 0.093), but a higher haemoglobin value before blood donation
      reduced the risk significantly to 0.712 per unit (1 g/dl). Therefore the age of
      the patient was less predictive compared to the haemoglobin value as to whether
      or not a blood transfusion had been necessary. CONCLUSION: The high security of
      homologous blood reached in the last years and the knowledge that autologous
      blood donation reduces the haemoglobin value before surgery has led to the
      procedure in our hospital only to perform autologous blood donation at the
      explicit request of the patient.

PMID- 16625452
TI  - [Long-term results after mediocarpal and total arthrodesis of the wrist--a
      matched paired study].
AB  - AIM: Indications for total wrist arthrodesis are still a matter of discussion.
      The aim of this study was to investigate the long-term results (mean 118 +/- 49.5
      months) of total wrist arthrodesis (TA) in comparison to mediocarpal arthrodesis
      (MA). METHOD: A paired study of the TA group and the MA group was performed
      including 22 patients after posttraumatic wrist arthrosis in each group.
      Subjective, objective and radiological parameters were assessed. In addition, the
      modified Mayo wrist score, the DASH score and the SF-36 were utilized. RESULTS:
      Mean pain did not differ significantly in both groups. Mean wrist function (DASH)
      was assessed better by MA patients (25.3 +/- 25.8) compared to TA patients (35.5
      +/- 25.9; p > 0.1). Mean total wrist motion in the MA group was 66.1 % of the
      opposite side. The average grip strength of the TA group was 85.5 % +/- 58.4 %
      and of the MA group 79.9 % +/- 25.4 % of the uninvolved wrist. The Mayo score of
      the MA group (56.4 +/- 12.4) was significantly higher than in the TA group (65.9
      +/- 16.3; p = 0.04). The SF-36 showed no significant difference between both
      groups. CONCLUSION: In self-assessment, pain was of higher importance then wrist
      motion. According to our findings the type of arthrodesis did not influence
      patient satisfaction. Total wrist arthrodesis should not be excluded
      categorically as a possible alternative to mediocarpal arthrodesis.

PMID- 16625453
TI  - [Current status of wrist arthrodesis].
AB  - AIM: In order to ascertain the value and future of wrist arthrodesis we assessed
      the results of 47 wrist arthrodeses performed at the Departments of Orthopaedic
      and Trauma Surgery of the University of Goettingen between 1980 and 1998. METHOD:
      In a retrospective analysis we examined the patients clinical and radiological
      records. Evaluating the results we used the score described by Lohmann and Buck
      Gramcko in order to consider function, pain, strength and assessment of the
      patient him/herself. RESULTS: 93.6 % of all cases could be examined. We found a
      wrist arthrodesis in posttraumatic arthritis in 22 cases and in rheumatoid
      arthritis in 25 cases. Plate (n = 30) and Rush-Pin osteosynthesis (n = 17) were
      used as surgical procedures. In all patients we found a successfully stabilised
      wrist, although in 3 trauma cases a further surgical procedure was necessary. A
      better function of the wrist was reached in every patient. The majority of the
      patients had no pain and an acceptable strength. The results obtained showed good
      and excellent results in 86.4 % of the wrist arthrodesis for post-traumatic
      arthritis and in 90.9 % for rheumatoid arthritis. CONCLUSION: The increase in
      quality of life, especially in patients suffering from rheumatoid arthritis,
      shows the procedure of wrist arthrodesis to be a still worthwile surgery.

PMID- 16625454
TI  - [Quality analysis of internet information on epicondylitis radialis humeri].
AB  - AIM: By means of conventional internet search engines we assessed the World Wide
      Web for the topic "epicondylitis radialis humeri" and analysed the content of the
      listed pages for their quality and transparency. METHODS: Three of the most
      frequently used internet search engines were utilised to search the World Wide
      Web for the terms "tennis arm", "tennis elbow" and "epicondylitis". The first 50
      listed internet addresses per search engine were scrutinised in respect to the
      authors' source, financier of the web page and whether commercial interests were
      evident. Furthermore, the medical content concerning radial epicondylitis was
      analysed using a 10-point score. RESULTS: After elimination of repetitive and not
      accessible internet pages, as well as web pages only giving links to further web
      sites or chat-rooms, we were able to evaluate 137 internet sites. The average
      content-score of all pages was low with 2.91 +/- 3.27 SD. Web-pages, where
      authorship could not be identified or where commercial interests were clearly
      evident, had the lowest content-scores. Sites authored by or associated with
      orthopaedic surgeons had a significantly higher content-score (6.84 +/- 3.17 SD)
      in comparison to other initiators of web-pages (p < 0.0001). CONCLUSION: The
      facts derived from the World Wide Web when searching for information on
      epicondylitis radialis humeri are mostly of low professional quality and
      transparency. Orthopaedic surgeons need to point out this problem to patients who
      additionally inform themselves on the internet. If the desire for browsing the
      web for further information concerning musculoskeletal pathology exists,
      orthopaedic surgeons should tell their patients which web sites are suitable.

PMID- 16625455
TI  - [Multicentric extra-abdominal fibromatosis: a rare case].
AB  - Extra-abdominal aggressive fibromatosis is a benign fibroblastic neoplasia with
      an infiltrative nature and a high tendency of local recurrence. Here, we report
      on a very rare case of multicentric fibromatosis. Low complaints led to
      considerable size of the tumours. The aim of the multimodal treatment was a limb
      salvage procedure. Adjuvant radiation therapy and chemotherapy was necessary
      because of the renunciation of wide resections in favour of the functionality of
      the limb.

PMID- 16625456
TI  - [Nora's lesion at the second metacarpal bone of a twelve-year-old female].
AB  - The extremely rare condition of bizarre parosteal osteochondromatous
      proliferation (BPOP) was first described in 1983 by the pathologist Nora, and a
      few more than 100 cases have since been reported. The lesion is defined as a
      reactive heterotopic ossification and is mostly found in the hands or feet of
      adults in the third decade of life, although it has also been described in long
      bones and in other age groups. A high rate of local recurrence of up to 50 % has
      been noted, but the lesion is benign and does not metastasise. An association
      with chromosomal rearrangements has recently been described. We here report the
      case of a 12-year-old girl with a BPOP at the second metacarpal bone, thus at an
      unusual age. The lesion was marginally resected after biopsy, but recurred
      locally within 2 years, resulting in subtotal resection of the second metacarpal
      bone, autologous fibula grafting and temporary external fixation. The clinical,
      plain radiographic and MRI appearance of the lesion and the prominent
      histological findings are described, and the difficulties in establishing the
      correct diagnosis in cases of BPOP are discussed.

PMID- 16625458
TI  - [Retrospective analysis of colorectal carcinomas reveals potential for
      improvement of diagnostic quality].
AB  - INTRODUCTION: The histopathological work-up of colorectal cancer is of critical
      importance for prognosis and therapy. Therefore we retrospectively analyzed all
      colorectal carcinomas diagnosed at our institution from January 2002 through
      March 2003. METHODS: 735 of a total of 777 carcinomas could be followed up. These
      tumors comprised 74 polypectomy specimens, 32 transanal microscopic surgery
      specimens, 322 surgical resection specimens analyzed at our own institution
      (subgroup A) and 263 surgical resection specimens that had been worked up at
      other pathological institutions (subgroup B) after the diagnosis of carcinoma had
      been established in our own institution in biopsies. 44 tumors were not treated
      locally until the end of the study. Quantitative quality parameters were analyzed
      statistically using Fisher's exact test. RESULTS: Between subgroups A and B
      significant differences were found within 1. the proportion of specimens with
      less than 12 lymph nodes examined (11 vs. 25 %), 2. for the detection of an R1
      situation despite macroscopic R0 resection (9 vs. 1 %), 3. the proportion of
      early colonic cancers (9 vs. 4 %), 4. of mucinous adenocarcinomas (19 vs. 4 %),
      5. of lymphatic (48 vs. 23 %) and venous invasion (25 vs. 8 %), 6. the frequency
      of a macroscopic description of mesorectum quality (85 vs. 14 %). In 7 of 32
      surgically treated patients with a high-risk carcinoma originally found within a
      polypectomy specimen, residual tumor was detected in the surgical resection
      specimen (at the polypectomy site and/or in regional lymph nodes). CONCLUSION:
      Due to retrospective analysis of colorectal cancer specimens we were able to
      identify potential for improvement of diagnostic quality. Furthermore our data
      underline the importance of an oncological resection, if a high risk carcinoma
      has been detected within a polypectomy specimen.

PMID- 16625459
TI  - [Socioeconomic characteristics, quality of life, and state of knowledge of
      patients with hepatitis C viral infection in Germany--socioeconomic aspects in
      hepatitis C].
AB  - BACKGROUND: Little is known as yet about the socio-economic consequences for
      patients with hepatitis C in Germany. AIMS AND METHODS: The study of the Deutsche
      Leberhilfe e. V., supported by the federal hepatitis competence net,
      prospectively analyzed questionnaires about quality-of-life, education and work
      situation, insurance, and various other socio-economical aspects of patients with
      chronic hepatitis C. The questionnaire included questions about the information
      status of patients concerning hepatitis C in general and their individual
      disease. Overall, 1500 questionnaires were distributed by clinics, general
      practitioners, patient-support groups and via the internet; 714 were sent back
      and analyzed. RESULTS: Most of the 714 patients were born in Germany; 56 % were
      women and 44 % men, with a mean age of 52 years and a hepatitis duration of 18
      years. More than 60 % of subjects younger than 65 years of age did not have a
      regular job, and 27 % were already retired. Only 47 % had a sufficient retirement
      insurance, whereas almost all had a health insurance. Only 12 % had an insurance
      covering work invalidity, and of those who had applied for the latter insurance,
      it was denied in 29 %. About 80 % of subjects reported that the hepatitis
      disturbed various aspects of their life. Only 4 % considered the public knowledge
      about hepatitis C as good or very good, but 80 % as bad or very bad. Of the
      subjects 40 % did not know how they had been infected; 37 % considered blood
      products as their infection mode, but only 10 % drug abuse. Almost all subjects
      knew that HCV cannot be transmitted via shaking hands, use of bathrooms, kisses
      or food (< 1 %, respectively). Surgery (17 %) and the dentist (15 %), however,
      were mentioned relatively often as a major risk for infection. About 80 % of
      subjects knew recent quantitative data on ALT and HCV-RNA, their genotype and the
      results of liver biopsy. Both mental and physical scores in the SF12
      questionnaire were markedly reduced by about one standard deviation in subjects
      with HCV infection when compared with the general German population. Mental and
      physical scores deteriorated with increases in inflammatory and fibrosis scores.
      Subjects with negative HCV-RNA and normal ALT had the best quality of life,
      whereas subjects with high levels of HCV-RNA and ALT had the worst. CONCLUSIONS:
      The data show that the public opinion is wrong when pretending that hepatitis C
      today is just a disease of drug addicts. Our analysis demonstrates for the first
      time that many HCV-infected subjects in Germany have problems with their
      insurance and jobs. German subjects are well informed about their infection
      including genotype, liver histology, ALT and HCV-RNA; on the other hand, there
      are information deficits and fears concerning the mode of infection. The recent
      analysis clearly shows that HCV-infected subjects consider the public information
      about the HCV infection as catastrophically bad. The recent data in addition show
      that elimination of HCV decisively ameliorates quality of life, whereas mental
      and physical health get increasingly worse with progressive liver disease and
      unsuccessful antiviral therapies.

PMID- 16625460
TI  - [Cholangitis with subphrenic abscess after complicated cholecystectomy due to
      occluded plastic stents].
AB  - A 62-year-old lady presented with fever and abdominal pain. History revealed
      cholecystectomy two years ago due to cholecystolithiasis, complicated by
      perforation of the common bile duct, leading to hepaticojejunostomy,
      jejunocholedochostomy, endoscopic retrograde insertion of two plastic stents and
      percutaneous drainage of bilioma. The patient was lost to follow-up until she
      presented two years later in the emergency room. ERC was performed. Both stents
      were occluded. After extraction dirty bile popped out. Injection of contrast
      medium showed stones in the remaining common bile duct and dilatation of the
      intrahepatic bile ducts and the interposed jejunum. After stone extraction a
      subphrenic intrahepatic fluid collection became visible when injecting contrast
      medium in the intrahepatic bile ducts. Pus was aspirated. The abscess was drained
      with a nasobiliary tube. Antibiotics were given. Temperature and CRP normalized.
      The nasobiliary tube was removed when the biliary fluid was clear. Recovery was
      uneventful with complete resolution of symptoms.

PMID- 16625461
TI  - [Early duodenal adenocarcinoma arising in gastric metaplasia treated by
      endoscopic resection].
AB  - Early duodenal carcinoma is a rare entity. Most duodenal carcinomas are diagnosed
      at a more advanced stage. This report describes the case of a 59-year-old lady
      with an early duodenal adenocarcinoma diagnosed at check-up gastroduodenoscopy in
      an outpatient clinic who was referred to us for further investigation and
      management. The initial upper endoscopy at our department revealed a type IIa+c
      lesion in the proximal duodenum (10 - 12 mm diameter, flat elevated lesion with
      central depression). Using chromoendoscopy and magnification endoscopy the lesion
      could be well demarcated and neoplastic changes in the architecture of the
      intestinal villi could be detected. After submucosal epinephrine-saline
      injection, the lesion was removed by endoscopic resection without complications.
      Histopathological examination revealed the rare entity of an early duodenal
      carcinoma arising from incomplete-type gastric metaplasia in the duodenum. In
      summary, the presented paper describes a case of successful endoscopic treatment
      of an early duodenal carcinoma arising from incomplete gastric metaplasia.

PMID- 16625462
TI  - [Pseudoaneurysm of the left hepatic artery as a complication of ERCP with
      sphincterotomy].
AB  - A pseudoaneurysm of the hepatic artery is a rare complication of interventional
      endoscopy or transhepatic puncture. The present case report describes a
      symptomatic pseudoaneurysm of the left hepatic artery following endoscopic
      retrograde cholangio-pancreatography (ERCP). The indication was a biliary
      pancreatitis, and it was treated by guide-wire-sphincterotomy and extraction of
      sludge with a Dormia basket. A superselective angiographic embolization was not
      necessary because of a spontaneous thrombotic obstruction of the pseudoaneurysm.

PMID- 16625463
TI  - [Gene therapy approaches to gastrointestinal tumors].
AB  - Gene therapy offers an elegant alternative to toxic chemotherapy regimens, mostly
      without severe side effects. Gene therapy for cancer was one of the first
      applications. Following the enthusiasm in the early 1990 s, a more rationale view
      is preferred today. This general review looks at the tools of gene therapy and
      their principle elements (vector, promoter, targeting, therapeutic genes). The
      principles of gene therapy such as gene-directed enzyme prodrug therapy (GDEPT)
      and gene-directed tumor vaccination are explained. Furthermore, published
      protocols and clinical studies in gastrointestinal oncology are reviewed.
      Finally, an outlook is given on the latest developments, some of them going
      beyond the realm of conventional gene therapy.

PMID- 16625464
TI  - [Are dilated intercellular spaces an invariable histological sign for gastro
      oesophageal reflux disease?].

PMID- 16625465
TI  - [Malnutrition in liver cirrhosis: impact of protein rich oral diet].

PMID- 16625469
TI  - [The state of pediatric urological outpatient surgery].
AB  - Economic requirements and the wishes of the patients have led to a clear increase
      in outpatient surgery. Besides the observance of legal conditions, a well-devised
      structure of organization is the prerequisite for a frictionless realization. The
      operating surgeon decides about the suitability of the patient, is responsible
      for a course without complications and takes on the postoperative care. The most
      frequent operations are circumcision, orchidopexy and the repair of inguinal
      hernias. Outpatient surgery stands out for a low rate of complications and a high
      satisfaction of the patients.

PMID- 16625470
TI  - [Induction of spermatogenesis in patients with non-obstructive azoospermia after
      antegrade sclerotherapy].
AB  - PURPOSE: The aim of this study was to prove the efficacy of antegrade
      sclerotherapy for varicocele testis in patients with azoospermia and in patients
      with cryptozoospermia (less than 0.1 million spermatozoons/mL ejaculate). We have
      investigated the induction of spermatogenesis in patients with non-obstructive
      azoospermia after antegrade sclerotherapy. MATERIALS AND METHODS: 20 consecutive
      patients who had been trying to beget a child over a period of one year or longer
      were chosen for this study. All patients suffered from non-obstructive
      azoospermia or from cryptozoospermia. We produced a control spermiogram for each
      patient before, 3 and 6 months after antegrade sclerotherapy. The postoperative
      spermiogram was done according to WHO criteria and was then compared to the
      preoperative data. RESULTS: 15 patients (75 %) were found to suffer from
      azoospermia preoperatively and 5 patients (25 %) from cryptozoospermia. Out of
      the 15 patients with initial azoospermia 8 (53 %) showed cryptozoospermia (OAT/OT
      syndrome) after antegrade sclerotherapy. Out of the 5 patients with the initial
      cryptozoospermia 3 (60 %) showed an improvement in the sperm count and motility
      criteria. CONCLUSIONS: Antegrade sclerotherapy for varicocele testis is a valid
      treatment option to isolate the spermatozoons from the ejaculate for
      extracorporeal fertilisation in patients with non-obstructive azoospermia.
      Complete normalisation of the spermiogram parameters, i.e., sufficient for
      natural child conception, cannot safely be achieved by this method.

PMID- 16625471
TI  - [Testicular metastases as primary manifestation of malignant melanoma at known
      melanocytoma].
AB  - BACKGROUND: Secondary tumors of the testes are rare. In about 15 % of the cases
      they are metastases of a malignant melanoma, there are about 30 reports of such
      cases in the literature. Most of them describe findings at post-mortem, in only 4
      of the previously described cases testicular metastases were the first
      manifestation of a melanoma. The transformation of a benign, meningeal
      melanocytoma into a malignant melanoma has only been described once world-wide.
      The problems in the diagnosis and therapy of this extremely rare tumor are
      discussed on the basis of a further patient with metastases of the testes as
      primary manifestation of a malignant melanoma. CASE REPORT: We report on a 74
      year-old man who presented with a relatively rapidly developing but less painful
      swelling of the left testicle. The case history disclosed operations 10 and 3.5
      year earlier for an apparently benign melanocytoma at the level of the 11th and
      12th thoracic vertebrae, a local recurrence with paraparesis was known at the
      time of admission. Sonography revealed an inhomogeneous tumor effecting the
      entire left testicle. Therapy comprised an inguinal, radical orchiectomy. The
      correct diagnosis was made histologically. Shortly after the operation, a
      diffuse, subcutaneous and hepatic metastases occurred. CONCLUSION: In the case of
      a primary manifestation a correct preoperative diagnosis is unusual. Radical
      orchiectomy is the treatment of choice for a suspected primary testicular tumor.
      The prognosis is accordingly poor. In elderly patients with unclear testicular
      tumors metastases from an (occult) tumor disease must be taken into
      consideration.

PMID- 16625472
TI  - [Acute abdominal pain due to a ventriculo-peritoneal shunt metastasis of an
      intracranial germ cell tumor].
AB  - INTRODUCTION: Extracranial metastases of pineal germinomas are rare. CASE REPORT:
      The case of a metastasis of a primary intracranial germ cell tumor via a
      temporary-ventriculo-peritoneal shunt as a cause of acute abdominal pain is
      reported. The germ cell tumor markers were useful in establishing the diagnosis.
      CONCLUSIONS: With an appropriate clinical history, intra-abdominal metastases via
      a temporary ventriculo-peritoneal shunt should be considered in the differential
      diagnosis of acute abdominal pain.

PMID- 16625473
TI  - [Distal stenosis of the ureter due to extrinsic endometriosis in a postmenopausal
      woman].
AB  - INTRODUCTION: Endometriosis in postmenopausal women is rare, especially in the
      urinary tract. Only a few cases have been described. CASE REPORT: A
      postmenopausal woman presented with left-sided ureteric obstruction.
      Intraoperatively an extrinsic endometriosis was found. In contrast to other
      cases, the patient had no history of endometriosis or estrogen therapy.
      CONCLUSION: This rare disease should also be considered in female patients in non
      reproductive age with symptoms of unclear hydronephrosis.

PMID- 16625474
TI  - [Circumcision with frenulum-plasty].

PMID- 16625475
TI  - [Funicolysis and orchidopexy].

PMID- 16625477
TI  - [Tissue engineering -- in vitro culture of reparative tissue].

PMID- 16625478
TI  - [Pulmonary tissue regeneration -- a hope for the future].

PMID- 16625479
TI  - [Reverse remodeling -- paradigm shift in the treatment of pulmonary
      hypertension].

PMID- 16625480
TI  - [BCGitis].

PMID- 16625481
TI  - [Stem cell transfer in myocardial infarction].

PMID- 16625482
TI  - [Atrial remodeling and anti-remodeling therapy in atrial fibrillation].

PMID- 16625483
TI  - [Transplantation of hepatocytes in liver failure].

PMID- 16625484
TI  - [Tissue regeneration and immunosuppression by mesenchymal stem cells].

PMID- 16625485
TI  - [Regeneration of renal tissue -- therapy of the future?].

PMID- 16625486
TI  - [Islet transplantation, stem cell transfer and regenerative therapy in diabetes
      mellitus].

PMID- 16625487
TI  - [Gastroesophageal reflux disease].

PMID- 16625488
TI  - [Fusion and privatisation of Giessen and Marburg University Hospitals in the
      network of Hessian academic medicine].

PMID- 16625489
TI  - [Fault of organisation in hospital and practice].

PMID- 16625496
TI  - Vascular endothelial growth factor, its receptors, and the tie receptors in the
      placental bed of women with preeclampsia, diabetes, and intrauterine growth
      retardation.
AB  - Placental bed vascular function is compromised in pregnancies complicated by
      preeclampsia (PE), intrauterine growth retardation (IUGR), and maternal diabetes
      mellitus (DM). We performed an immunohistochemical analysis of vascular
      endothelial growth factor (VEGF), its receptors (VEGFR) -1 and -2, and the Tie-1
      and -2 receptors in cryostat tissue sections of the placental bed from healthy
      women (n = 5) and women with PE (n = 5), IUGR (n = 5), and DM (n = 5). VEGF
      immunoreactivity was stable between the study groups. VEGFR-1 immunoreactivity in
      the myometrial vascular smooth muscle cells was strongest in the controls. In the
      myometrial cells, the strongest VEGFR-2 immunoreactivity was seen in women with
      IUGR. In the decidual vascular endothelial cells, the strongest Tie-1
      immunoreactivity was observed in healthy women and in those with DM. Alterations
      in the placental bed expression of VEGFR-1, VEGFR -2, and Tie-1, but not of VEGF
      and Tie-2, may be associated with PE, IUGR, or DM.

PMID- 16625497
TI  - Primary psoas abscess in a neonate.
AB  - A case of primary ileo-psoas abscess in a neonate is presented. Psoas abscess is
      extremely uncommon in this age group. The role of ultrasound and computed
      tomography in the diagnosis is demonstrated, and the need for antibiotic therapy
      is emphasized for a minimum period of 2 weeks.

PMID- 16625498
TI  - Prenatal diagnosis of conotruncal malformations: diagnostic accuracy, outcome,
      chromosomal abnormalities, and extracardiac anomalies.
AB  - The purpose of this study was to determine whether continuing experience in
      prenatal diagnosis of conotruncal malformations (CTMs) has resulted in improved
      diagnostic accuracy and outcome. Previous reports have demonstrated particular
      difficulty with ascertainment of the spatial relationship of the great arteries
      in patients with CTM. The prognosis for fetuses with CTM was poor. Medical
      records of 113 consecutive fetuses in whom a CTM (tetralogy of Fallot [TOF],
      double-outlet right ventricle [DORV], type B aortic arch interruption,
      transposition of the great arteries [TGA], and persistent truncus arteriosus
      [TA]) was diagnosed antenatally between 1994 and 2003 were reviewed. The
      diagnosis of the 91 fetuses with CTM included TOF (n = 32), TGA (n = 29), DORV (n
      = 22), and TA (n = 8). The great arterial spatial relationship was diagnosed
      accurately in 84 of the 91 (92%) live-born infants. In the other seven infants
      with DORV, the great arterial spatial relationship was identified inaccurately.
      The overall survival to 30 days was 85 of 91 (93%). Twenty-three of 91 (25%)
      patients had extracardiac anomalies. Genetic diagnosis (amniocentesis) was
      obtained in 63 of 94 patients; 11 (17%) had chromosomal abnormalities. Maternal
      glucose tolerance results were obtained in 65 of the 91 patients and were
      abnormal in 25 of 65 (38%). Prenatal diagnostic accuracy of conotruncal
      malformations is excellent; the arterial spatial relationship of DORV remains
      problematic. The populations of fetuses with CTMs who continue to develop to term
      have an excellent prognosis.

PMID- 16625499
TI  - A method for quantifying birthweight discordance in quadruplets and potential use
      in predicting early mortality.
AB  - We describe an approach to quantify birthweight discordance in quadruplets and
      assessed its potential use in predicting infant mortality. Retrospective cohort
      study on quadruplets delivered in the United States from 1995 through 2000
      inclusive. The main outcome measures were infant, neonatal, and postneonatal
      mortality. A total of 2692 quadruplet live births (673 complete clusters) with
      complete information on gestational age, birthweight, and survival within the
      first year. Of the total 673 quadruplet clusters, discordance occurred in 180
      sets (26.7%). The predominant discordant type was a single discordant individual
      within a cluster (177 sets or 99.8%), whereas only three sets (0.2%) recorded up
      to two discordant quadruplets within a cluster. The period of pronounced risk for
      the occurrence of birthweight discordance was between 28 and 35 gestational
      weeks. Discordant individuals exhibited elevated risk for infant (adjusted odds
      ratio [aOR] = 2.1; 95% confidence interval [CI], 1.4 to 3.0), neonatal (aOR =
      1.8; 95% CI, 1.2 to 2.6), and postneonatal (aOR = 2.9; 95% CI, 1.1 to 8.4)
      mortality. After adjusting for small for gestational age, the risk for
      postneonatal mortality among discordant infants quadrupled (aOR = 4.1; 95% CI,
      1.5 to 10.8). The population-attributable risks were 18, 20, and 46% for
      neonatal, infant, and postneonatal mortality, respectively. The new method is
      predictive of mortality at all stages of infancy. Discordance accounts for 18 to
      46% of all quadruplet deaths during infancy in the United States.

PMID- 16625500
TI  - Anticardiolipin and anti-beta2 glycoprotein I antibodies in infants born to
      mothers with antiphospholipid antibody-positive autoimmune disease: a follow-up
      study.
AB  - Infants born from mothers with antiphospholipid antibody (aPL) -positive
      autoimmune disease were prospectively evaluated for anticardiolipin and anti
      beta2 glycoprotein I antibodies (group 1) and for growth and neurological
      development. The results were compared with those obtained from two age-matched
      control groups (group 2 and 3). All infants were negative for anticardiolipin at
      12 months of life, whereas 14 (63.6%), eight (33.3%), and 10 (55.5%) of infants
      from group 1, 2, and 3, respectively, were positive for anti-beta2 glycoprotein
      I. At follow-up, all infants had normal growth and neurological development. No
      thrombotic complication was observed. The negativity of anticardiolipin in all
      infants at 12 months suggests that anticardiolipin detection is the best assay to
      evaluate the disappearance of maternal aPL and to estimate the potential risk of
      thrombosis associated with these antibodies. The high rate of anti-beta2
      glycoprotein I positivity in all three groups of infants may indicate that the
      synthesis of this antibody is stimulated by aspecific factors.

PMID- 16625501
TI  - Effect of introduction of synchronized nasal intermittent positive-pressure
      ventilation in a neonatal intensive care unit on bronchopulmonary dysplasia and
      growth in preterm infants.
AB  - The objective of this study was to evaluate the incidence of bronchopulmonary
      dysplasia (BPD), nutritional intake, and growth in premature infants receiving
      synchronized nasal intermittent positive-pressure ventilation (SNIPPV) versus
      nasal continuous positive airways pressure (NCPAP) after extubation, at an
      institution with no prior experience with SNIPPV. This was a retrospective case
      control study of infants (born May 2000 to December 2003) at < or = 32 weeks
      gestation. Extubation to SNIPPV was performed in accordance with a standardized
      protocol. Infants in the control group were extubated to NCPAP, as per standard
      nursery practice. There were no significant differences in the maternal
      characteristics, antenatal corticosteroid use, mode of delivery, gestational age,
      birthweight, male gender, Apgar scores at 1 and 5 minutes, number of surfactant
      doses, and duration of endotracheal tube PPV between infants in the control group
      (n = 30) and those extubated to SNIPPV (n = 30). The duration of NCPAP (median
      [range]: control versus SNIPPV, 601 [24 to 1270] versus 230.5 [36 to 1200] hours;
      P < 0.001) and supplemental oxygen (mean +/- standard error of the mean: 84.10 +/
      6.43 versus 63.68 +/- 5.34 days; p = 0.02) was significantly lower in the SNIPPV
      group. The number of infants with BPD was significantly less in the SNIPPV group
      (73% versus 40%; p < 0.01). There were no differences between the two groups in
      total days on parenteral nutrition, caloric intake (total, carbohydrate, protein,
      or fat), or weight gain. Our results show that introduction of SNIPPV in a
      neonatal intensive care unit resulted in infants having significantly less need
      for supplemental oxygen and decreased BPD, without affecting their weight gain or
      the incidence of other short-term morbidities.

PMID- 16625502
TI  - Iliofemoral-popliteal phlebothrombosis in twin pregnancy treated with cesarean
      section and thrombectomy in the same act: a case report.
AB  - A case is presented of a 39-year-old primigravida who developed iliofemoral
      popliteal thrombosis in the 34th week of twin pregnancy. Thrombectomy by use of a
      Fogarty catheter with previous protection from thrombus embolization by proximal
      placement of temporary occlusion was performed at the same time as the cesarean
      section for completion of premature delivery.

PMID- 16625503
TI  - Troponin I as a biomarker of cardiac injury in neonates with idiopathic
      respiratory distress.
AB  - Troponin I (TnI), an inhibitory protein complex located on the actin filament of
      cardiac muscle, has become a specific marker of myocardial damage. Troponin has
      been studied in a wide range of clinical settings. However, many questions are
      still unanswered, especially in preterm neonates with the most common pathology
      at birth, such as idiopathic respiratory distress syndrome (IRDS). The aim of
      this study was to establish a reference range for cardiac TnI for healthy preterm
      infants and serum levels in sick preterm infants with IRDS. Echocardiography was
      performed and TnI serum levels were measured at a median age of 62 hours of life
      in three groups of healthy preterm infants (n = 10), and ventilated infants with
      moderate (n = 15) and severe IRDS (n = 15). Ventilated infants with idiopathic
      moderate IRDS had significantly different cardiac parameters (R/L ejection
      fraction, R/L stroke volume, R/L cardiac output; p < 0.05) and significantly
      higher cardiac TnI levels than healthy infants (0.037 versus 0.01 microg/mL; p <
      0.05). Furthermore, infants with severe IRDS had higher TnI concentrations than
      infants with moderate IRDS (0.26 versus 0.037 microg/mL; p < 0.05). The results
      of this study show that increased TnI serum levels in sick preterm infants with
      IRDS are explained by myocardial injury or dysfunction due to impaired arterial
      oxygenation or reduction in cardiac output during treatment with mechanical
      ventilation. These results suggest that cardiac TnI may be a useful, specific
      marker for myocardial damage in preterm neonates with IRDS.

PMID- 16625504
TI  - [Acute onset of cerebellar dysfunction in infancy].

PMID- 16625505
TI  - [Treatment of neuropathic pain in neurology units. The PREVADOL study].
AB  - INTRODUCTION: Neuropathic pain (NPP) is defined as a pain started or caused by an
      injury to or dysfunction of the nervous system. Its treatment is different to
      that of nociceptive pain since it does not respond to conventional analgesics or
      non-steroidal antiinflammatory drugs. AIM: To describe the treatment being
      received by patients with NPP in the daily clinical practice of the specialist in
      neurology. PATIENTS AND METHODS: An observational, epidemiological, cross
      sectional study was conducted in 36 neurology units (24 extra-hospital and 12
      belonging to hospitals). We collected the clinical data and the treatment
      administered to the first 20 patients with NPP to visit the neurology units over
      a period of 20 consecutive working days. RESULTS: Data were collected for a total
      of 451 patients with NPP. The pharmacological groups most frequently used in
      patients with NPP attended in neurology units are antiepileptics (71%) and
      antidepressants (15%). Of these patients, 60% were being treated with a single
      drug (an antiepileptic agent in 84.5% of cases; antidepressants in 10.3%). Two
      pharmacological treatments were being received by 23.7%, and 2.3% of patients
      were given treatment involving three or more pharmacological agents. A total of
      30% received non-pharmacological treatments, especially physiotherapy (50.4%).
      CONCLUSIONS: Most patients with NPP attended in neurology units follow first
      order pharmacological treatments (antiepileptics or antidepressants). Over half
      the patients are controlled with monotherapy, usually with an antiepileptic
      agent. Non-pharmacological treatments (especially physiotherapy) are used in a
      third of the patients.

PMID- 16625506
TI  - [Evoked potentials in a population of children below 1,500 grams at birth: a
      description and probabilities].
AB  - INTRODUCTION: Bioelectrical behaviour was studied in a group of low birth weight
      children. AIM: To evaluate whether the characteristics of the waves of the brain
      potentials in these children, who weighed less than 1500 g at birth and
      experienced anomalous circumstances and events during their perinatal period,
      would help reach an early diagnosis of the possible developmental disorders they
      might suffer later on in life. SUBJECTS AND METHODS: Both visual and auditory
      cerebral evoked potentials were recorded in a group of children born underweight
      and the results were compared with the findings from another group of healthy
      children who were born in normal physiological conditions and were apparently
      free of any kind of pathology. RESULTS: In the waves and locations that were
      examined, the problem group displayed latencies that were longer than those of
      the control group; in contrast, no statistically significant differences were
      found in the amplitude, regardless of the location. Low gestational age and lower
      weight made latencies longer, but no relationship was found between latencies and
      the other perinatal features that were studied. CONCLUSIONS: Children with low
      weight at birth have slower wave latencies than normal children. This slowing,
      which is inversely proportional to the weight and weeks of gestation, is
      considered to be an anomalous sign that could be related to brain immaturity,
      delayed development or to disorders affecting myelination. Moreover, the
      amplitude, which has received far less attention from researchers, is usually
      shorter in these processes, although in our study we found no differences with
      the group of healthy children--only very slightly in the P300, in the weeks and
      the weight, and the N100 only in one location with respect to weight. Since these
      children usually have developmental disorders, the use of evoked potentials could
      be a very useful tool in their detection and ensuing therapy.

PMID- 16625507
TI  - [Clinical and videofluoroscopic evaluation of swallowing in patients with spastic
      tetraparetic cerebral palsy and athetosic cerebral palsy].
AB  - AIM: To evaluate and to compare the findings of oral and pharyngeal phases of
      swallowing in children with both spastic tetraparetic cerebral palsy (STCP) and
      with athetosic cerebral palsy (ACP). PATIENTS AND METHODS: 11 children were
      evaluated, with their ages ranging from 10 months to 8 years old, through both
      clinical assessment and videofluoroscopic evaluation. RESULTS: The children with
      STCP were more involved at the neurologic, clinical and speech-language and
      hearing aspects. At the oral phases all the children had presented some
      involvement. At the pharyngeal phases the clinical signs of aspiration were
      identified in 10 children. It was observed aspirations in 80% of children with
      STCP and in 67% with ACP. The changes on swallowing were similar in both cerebral
      palsy groups, but the performance of the children with STCP was inferior.
      CONCLUSION: The videofluoroscopy was an important method which makes possible the
      verification of aspirations, helping the professionals at the therapeutical
      program for these children.

PMID- 16625508
TI  - [Cerebellar atrophy following acute Mycoplasma pneumoniae cerebellitis].
AB  - INTRODUCTION: Acute cerebellitis is an uncommon complication following Mycoplasma
      pneumoniae infection. A benign and self-limited course has been described in the
      few reports found of this association. CASE REPORTS: We report two patients with
      an apparently M. pneumoniae-induced acute cerebellitis that resulted in
      cerebellar atrophy. Patients presented with a cerebellar syndrome including
      ataxia, hypotonia, dysarthric speech and dysmetria, which were preceded by signs
      of respiratory infection. Initial brain magnetic resonance imaging (MRI) in case
      1 was normal but in case 2 it displayed striking cerebellar swelling, small
      fourth ventricle and supratentorial ventriculomegaly which was self-limited and
      did not require neurosurgical intervention. Serological studies confirmed a
      recent M. pneumoniae infection. Case 1 has followed an unfavourable clinical
      course, with incomplete resolution of cerebellar dysfunction, while case 2 has
      remained asymptomatic. Follow-up brain MRI have demonstrated prominent cerebellar
      atrophy in both patients. CONCLUSIONS: M. pneumoniae infection should be
      considered in those patients with acute cerebellitis showing an incomplete
      resolution of cerebellar dysfunction or those who develop early cerebellar
      atrophy. The presenting MRI findings do not seem to predict final neurological
      outcome.

PMID- 16625509
TI  - [Anticholinesterases in the treatment of Alzheimer's disease].
AB  - INTRODUCTION: Among the numerous pathophysiological theories that attempt to
      explain the development of Alzheimer's disease (AD) there are two facts that
      stand out above the rest: on the one hand, the formation of neurofibrillary
      tangles inside cells and, on the other, the extra-cellular deposition of beta
      amyloid protein. These two mechanisms lead to neurodegeneration and the death of
      cells by means of a process called 'apoptosis' or 'programmed cell death'. In the
      early stages of this neurodegenerative process it is more pronounced in
      cholinergic-type brain centres. This led to the formulation of the so-called
      cholinergic theory of Alzheimer, which provides the rationale behind the use of
      the drugs that are currently available to treat this disease, namely,
      acetylcholine esterase (AChE) inhibitors (rivastigmine, donepezil and
      galanthamine). DEVELOPMENT AND CONCLUSIONS: We review the possible
      pharmacological approaches that could help to prevent or delay cell death, and
      which act on the mechanisms involved in the production of neurofibrillary tangles
      or the deposition of beta-amyloid protein. We also review the main
      characteristics of cholinergic neurotransmission, which will help us to
      understand the therapeutic approaches that have been applied in an attempt to
      enhance deficient cholinergic neurotransmission. One of the most notable of these
      is the amount of attention recently being paid to the enzyme AChE, which
      increases the bioavailability of the neurotransmitter in the cholinergic synapses
      by preventing the hydrolysis of acetylcholine; these are the only drugs currently
      available for the symptomatic treatment of this disease.

PMID- 16625510
TI  - [New therapeutic options in Alzheimer's disease].
AB  - INTRODUCTION: At present, cholinesterase inhibitors constitute the basis for
      therapy of Alzheimer's disease (AD); these drugs were rationally introduced given
      the loss of central cholinergic neurotransmission, even though there are many
      other systems affected in AD, including glutamatergic pathway. DEVELOPMENT: In
      addition to the loss of central cholinergic neurotransmission, biochemical
      evidence suggests glutamatergic dysfunction in AD and thus, therapeutic
      strategies directed at the glutamatergic system may be useful. These drugs
      include milacemide, cicloserine and ampakines (positive modulation) and memantine
      (negative modulation). Lithium seems to be a promising agent in AD, although the
      mechanism of action is poorly understood. Finally anti-inflammatory agents may be
      another therapeutic approach to AD. CONCLUSION: In addition to drugs acting on
      the cholinergic system, a large number of drugs with different mechanism could be
      used for the treatment and prevention of AD.

PMID- 16625511
TI  - [Treatment of non cognitive symptoms of Alzheimer's disease].
AB  - INTRODUCTION AND DEVELOPMENT: Owing to their functional repercussions, the
      secondary or non-cognitive symptoms displayed by patients with Alzheimer's
      disease (AD) are very important both for the patients themselves and for the work
      of the caregiver. In this article we review the treatment of some of them, such
      as psychotic disorders and depressive symptoms. Atypical neuroleptic drugs are
      the preferred treatment for symptoms such as delusions, hallucinations, agitation
      and aggressive behaviour. The most widely used are olanzapine and risperidone.
      Their pharmacological characteristics, therapeutic effectiveness and side effects
      are reviewed. CONCLUSIONS: Broader and better designed clinical studies are
      required to evaluate their usefulness. Recent reports, from 2004, have described
      a significant increase in the mortality rate (3.5 vs. 1.5%) and in the risk of
      suffering a stroke (1.3 vs. 0.4%) in elderly demented patients associated to the
      use of olanzapine and risperidone. The good tolerance and absence of
      anticholinergic effects of the serotonin reuptake inhibitors, fluoxetin and
      paroxetine, make them the first-choice medication for the treatment of the
      depressive symptoms in AD. Despite their widespread use, the evidence currently
      available with respect to their therapeutic effectiveness is not very convincing
      and clinical trials with a wider scope and a better design need to be carried
      out.

PMID- 16625512
TI  - [Mescaline and the San Pedro cactus ritual: archaeological and ethnographic
      evidence in northern Peru].
AB  - INTRODUCTION: The San Pedro cactus contains the alkaloid mescaline and other
      derivates of phenethylamine with hallucinogenic properties. This cactus was used
      throughout history by a number of different pre-Columbine cultures and
      civilisations that settled in northern Peru. In this article we review the ethno
      archaeological and ethno-historical evidence of the ritual use of the San Pedro
      cactus in the pre-Columbine cultures, and these findings are compared with the
      information provided by current ethnographical studies. DEVELOPMENT: The longer a
      cactus has been stored, the stronger and the higher its content in mescaline
      derived alkaloids will be. Archaeological evidence has been found of the use of
      San Pedro for magical-religious purposes in the following pre-Columbine cultures:
      Cupisnique (1500 BC), Chavin (1000 BC), Moche (100-750 AD) and Lambayeque (750
      1350 AD). Today's master shamans use San Pedro on altars ('mesas') erected for
      healing rites in order to treat enchantment and bad luck. The mesa follows a
      sophisticated ritual: 'levantar' (raise) or sniff tobacco with alcohol, ingest
      San Pedro, pinpoint the diseases, cleanse the evil and 'florecer' (flourish) the
      sick person. The mesa rite is performed in the early hours of Tuesdays and
      Fridays, which are sacred days in the Andean religions. San Pedro is sometimes
      replaced by an infusion of plants and seeds that contain hallucinogenic
      components, such as ayahuasca and the 'mishas' (Brugmansia sp.). CONCLUSIONS: The
      ancient tradition of using the San Pedro cactus for healing and hallucinogenic
      purposes has remained part of the culture in Andean shamanism up to the present
      day.

PMID- 16625514
TI  - [Acute cerebellitis and secondary hydrocephalus].

PMID- 16625515
TI  - [Hemicerebellitis versus cerebellar tumour].

PMID- 16625516
TI  - [Cerebellar seizures: can we speak of such a thing?].

PMID- 16625517
TI  - [Anterior encephalocele in a human embryo resulting from an ectopic pregnancy].

PMID- 16625518
TI  - Estimating incidence of HIV infection in childbearing age African women using
      serial prevalence data from antenatal clinics.
AB  - Ades and Medley provided the first flexible method for estimating age- and time
      specific HIV incidence using HIV prevalence data collected among pregnant women
      and adjusting for the effect of differential selection between infected and
      uninfected women. This paper extends the approach proposed by these authors. We
      used a parametric model that allows the relative inclusion rate to depend on both
      age, calendar time, and duration of HIV infection. We developed a two dimensional
      penalized log-likelihood approach for estimating time- and age-specific incidence
      using a binomial likelihood function and a quadratic roughness penalty which
      allows smoothing over both age and time. Identifiability of the model parameters
      and effect of sample size are studied through simulations. The method is
      illustrated using prenatal HIV testing data recorded from 1995 to 2002 in
      Abidjan, Cote d'Ivoire, to estimate the HIV annual incidence rate among women
      aged 12-40 year old, from the beginning of the epidemic to 2002. We show that
      estimated incidence rates are highly dependent on hypotheses made to model the
      relative inclusion rate. Despite this dependency, the application of the method
      leads to new and accurate findings on HIV incidence qualitative features in
      Abidjan. We highlight the relevance of such a method in monitoring the dynamics
      of HIV epidemic in Africa which is essential for planning vaccine trials and
      future treatment needs, and for assessment of prevention policy.

PMID- 16625519
TI  - East-west: does it make a difference to hospital efficiencies in Ukraine?
AB  - Ukraine's history has given it a split personality (e.g. divergent cultural
      influences on economic and managerial behavior), as was observed in the recent
      political developments both prior to and following the December 2004 elections.
      Eastern regions were heavily influenced by Russo-Soviet rule, while western
      regions have more of a European outlook. This study, which is largely
      exploratory, compares recent trends in hospital efficiency in Ukraine to see if
      this split personality manifests itself in differential rates of improvement.
      Given the inflexibility of Soviet-style planned economies, it is hypothesized
      that western regions will show greater improvement in economic efficiency that
      can be attributed to higher levels of managerial and medical entrepreneurship.
      Data for this study comes from three oblasts (i.e. geopolitical regions), one in
      the west and two in the east, spanning from 1997 to 2001. Data envelopment
      analysis (DEA) was used to estimate technical efficiency for the hospitals. After
      correcting for bias, a second-stage Tobit regression was estimated. Results
      indicate that hospitals in the west improved efficiencies, while those in the
      east stayed constant. These western areas of the nation, being more amenable to
      western management and medical 'business' practice, may be quicker to pick up on
      new techniques to increase healthcare delivery efficiencies. This may stem from
      the more limited effects of a shorter history of incorporation into a Soviet
      style planned and controlled economy in which individual decision-making and
      entrepreneurship was suppressed in favor of central decision-making by the state.

PMID- 16625520
TI  - Analysis of antiretroviral immunotherapy trials with potentially non-normal and
      incomplete longitudinal data.
AB  - For many HIV-infected patients, use of antiretroviral therapy (ART) results in a
      sustained suppression of plasma viral load to undetectable levels. However, due
      to lack of antigenic stimulation, this may also result in a gradual loss of cell
      mediated immune (CMI) responses that help control HIV infection. In concept,
      augmenting ART with periodic administrations of an HIV vaccine that boosts CMI
      responses could enhance control of viral replication. Researchers are designing
      'antiretroviral immunotherapy' (ARI) trials to test this hypothesis. In a typical
      ARI trial, HIV-infected patients with sustained viral suppression will receive
      inoculations of an experimental HIV vaccine or a placebo, and subsequently stop
      taking their antiretroviral drugs. The goal is to assess whether plasma viral
      loads during the ART interruption phase are generally lower in the vaccine group.
      Assessment of a vaccine effect will be challenging if some subjects resume ART or
      drop out before the end of the treatment interruption phase. To tackle this
      'missing' data problem and potential non-normality of the viral loads in ARI
      trials, we propose a two-step approach: multiple imputation of the missing values
      followed by use of the Wei-Lachin method with Wilcoxon scores. We use a numerical
      example and extensive simulations to illustrate the robustness and power
      advantages of our proposed method compared with other methods for incomplete
      longitudinal data, including REML, weighted GEE, last observation carried
      forward, and 'worst-rank' methods. Our proposed method is general enough for the
      robust analysis of longitudinal data in other therapeutic areas as well.

PMID- 16625521
TI  - Longitudinal variable selection by cross-validation in the case of many
      covariates.
AB  - Longitudinal models are commonly used for studying data collected on individuals
      repeatedly through time. While there are now a variety of such models available
      (marginal models, mixed effects models, etc.), far fewer options exist for the
      closely related issue of variable selection. In addition, longitudinal data
      typically derive from medical or other large-scale studies where often large
      numbers of potential explanatory variables and hence even larger numbers of
      candidate models must be considered. Cross-validation is a popular method for
      variable selection based on the predictive ability of the model. Here, we propose
      a cross-validation Markov chain Monte Carlo procedure as a general variable
      selection tool which avoids the need to visit all candidate models. Inclusion of
      a 'one-standard error' rule provides users with a collection of good models as is
      often desired. We demonstrate the effectiveness of our procedure both in a
      simulation setting and in a real application.

PMID- 16625522
TI  - Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of
      patients with adjustment disorders with anxiety: a double-blind controlled study
      in general practice.
AB  - Adjustment Disorders With Anxiety (ADWA) account for almost 10% of
      psychologically motivated consultations in primary care. The aim of this double
      blind randomised parallel group study was to compare (non-inferiority test) the
      efficacies of etifoxine, a non-benzodiazepine anxiolytic drug, and lorazepam, a
      benzodiazepine, for ADWA outpatients followed by general practitioners. 191
      outpatients (mean age: 43, female: 66%) were assigned to receive etifoxine (50 mg
      tid) or lorazepam (0.5-0.5-1 mg /day) for 28 days. Efficacy was evaluated on days
      7 and 28 of the treatment. The main efficacy assessment criterion was the
      Hamilton Rating Scale for Anxiety score (HAM-A) on Day 28 adjusted to Day 0. The
      anxiolytic effect of etifoxine was found not inferior to that of lorazepam (HAM-A
      score decrease: 54.6% vs 52.3%, respectively, p=0.0006). The two drugs were
      equivalent on Day 28. However, more etifoxine recipients responded to the
      treatment (HAM-A score decreased by >or=50%, p=0.03). Clinical improvement (based
      on Clinical Global Impression scale CGI, Social Adjustment Scale Self-Report SAS
      SR, and Sheehan scores) was observed in both treatment arms, but more etifoxine
      patients improved markedly (p=0.03) and had a marked therapeutic effect without
      side effects as assessed by CGI, p=0.04. Moreover, 1 week after stopping
      treatment, fewer patients taking etifoxine experienced a rebound of anxiety,
      compared to lorazepam (1 and 8, respectively, p=0.034).

PMID- 16625523
TI  - Statistical methodologies in psychopharmacology: a review.
AB  - There has been a greatly increased interest in statistical methods in the
      psychiatric research and its applications over the past few decades, in parallel
      with advances in computers and statistical software. This review aims to describe
      the main topics related to statistical methods in psychopharmacology, namely
      nature of statistics in medicine, problems in data analysis, statistical
      modelling, developments in statistical technology, statistical reporting and meta
      analysis.

PMID- 16625524
TI  - Clinical outcome in patients with bipolar I disorder, obsessive compulsive
      disorder or both.
AB  - BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive
      (OCD) and other anxiety disorders, but the impact of such comorbidity on long
      term outcome has not been evaluated systematically. METHODS: Extensive follow-up
      assessments were carried out at 4.3 years after index hospitalizations in a mixed
      BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20)
      alone. RESULTS: At follow-up, ratings of functional status were similar across
      groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9
      times more frequent among comorbid than OCD patients. OCD symptoms averaged 150%
      more severe in OCD than comorbid subjects, and were not measured in BPD subjects.
      CONCLUSIONS: Despite potential sampling bias with previously hospitalized
      subjects, the findings suggest that comorbid BPD-OCD patients may be clinically
      more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not
      negatively impact the long-term clinical outcome.

PMID- 16625525
TI  - A 12 to 24 weeks pilot study of sertraline treatment in obese women binge eaters.
AB  - Previous studies tested the efficacy of sertraline in Binge Eating Disorder (BED)
      over a period of 6 weeks. The present open study assesses the efficacy of
      sertraline over a period of 24 weeks in obese persons with binge eating behaviour
      (with or without the full criteria for BED) confirmed by high scores on the Binge
      Eating Scale (BES). Thirty-two obese outpatients (14 with BED and 18 without full
      criteria for BED), without co-occurring psychiatric comorbidities, were treated
      with sertraline (dose range 100-200 mg/d). Subjects were assessed at baseline and
      at 8, 12 and 24 weeks of treatment for number of binges, weight and
      psychopathology. After 8 weeks of treatment a significant improvement in the BES
      score and a significant weight loss emerged. These results were maintained over
      24 weeks. A moderate drop out rate was detected, but no significant association
      with the severity of side effects was found. Further studies are needed to
      confirm the usefulness of sertraline in the treatment of patients with BED and
      also in binge eaters with a less severe eating psychopathology.

PMID- 16625526
TI  - The role of education in biostatistical consulting.
AB  - Medical students, residents, postdoctoral fellows, and faculty commonly consult
      with biostatistical experts about study design and data analysis when conducting
      clinical research. The role of biostatistical training during these consultations
      is examined, and characterizations of the connections between biostatistical
      consultation and education are reviewed. The presence and kinds of teaching
      efforts during biostatistical consults at four academic research institutions
      over various periods of time between 1999 and 2005 (237 consultations in total)
      were recorded and are described. By site, 67, 70, 78, and 100 per cent of the
      consulting sessions included biostatistical training, with an overall 78 per cent
      (95 per cent CI: 73-83 per cent) of consultations including an educational
      component when all consultations were combined. Training covered a wide range of
      biostatistical topics. Seventy-five per cent of the consultations with faculty
      (120/161), 79 per cent with fellows and residents (31/39), and 100 per cent with
      medical students (10/10) included some degree of instruction in study design or
      statistical analysis topics. Results show that both the need and the opportunity
      exist for specialized biostatistical instruction during one-on-one sessions
      between a consulting biostatistician and physicians, medical students, and
      research staff. Academic researchers are ideally positioned to absorb this kind
      of training when they initiate a request for assistance with their own research
      project.

PMID- 16625527
TI  - Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute
      asthma.
AB  - BACKGROUND: In acute asthma inhaled beta2-agonists are often administered to
      relieve bronchospasm by wet nebulisation, but some have argued that metered-dose
      inhalers with a holding chamber (spacer) can be equally effective. Nebulisers
      require a power source and need regular maintenance, and are more expensive in
      the community setting. OBJECTIVES: To assess the effects of holding chambers
      (spacers) compared to nebulisers for the delivery of beta2-agonists for acute
      asthma. SEARCH STRATEGY: We last searched the Cochrane Airways Group trials
      register in January 2006 and the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 4, 2005). SELECTION CRITERIA: Randomised trials in
      adults and children (from two years of age) with asthma, where spacer beta2
      agonist delivery was compared with wet nebulisation. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently applied study inclusion criteria (one
      reviewer for the first version of the review), extracted the data and assessed
      trial quality. Missing data were obtained from the authors or estimated. Results
      are reported with 95% confidence intervals (CI). MAIN RESULTS: This review has
      been updated in January 2006 and four new trials have been added. 2066 children
      and 614 adults are now included in 25 trials from emergency room and community
      settings. In addition, six trials on in-patients with acute asthma (213 children
      and 28 adults) have been reviewed. Method of delivery of beta2-agonist did not
      appear to affect hospital admission rates. In adults, the relative risk of
      admission for spacer versus nebuliser was 0.97 (95% CI 0.63 to 1.49). The
      relative risk for children was 0.65 (95% CI: 0.4 to 1.06). In children, length of
      stay in the emergency department was significantly shorter when the spacer was
      used, with a mean difference of -0.47 hours (95% CI: -0.58 to -0.37). Length of
      stay in the emergency department for adults was similar for the two delivery
      methods. Peak flow and forced expiratory volume were also similar for the two
      delivery methods. Pulse rate was lower for spacer in children, mean difference 
      7.6% baseline (95% CI: -9.9 to -5.3% baseline). AUTHORS' CONCLUSIONS: Metered
      dose inhalers with spacer produced outcomes that were at least equivalent to
      nebuliser delivery. Spacers may have some advantages compared to nebulisers for
      children with acute asthma.

PMID- 16625528
TI  - Replacement arthroplasty versus internal fixation for extracapsular hip fractures
      in adults.
AB  - BACKGROUND: Internal fixation, commonly used for extracapsular hip fractures, may
      fail particularly in unstable fractures. Replacement of the hip using
      arthroplasty, often used for intracapsular fractures, has been used as an
      alternative. OBJECTIVES: To compare replacement arthroplasty with internal
      fixation for the treatment of extracapsular hip fractures in adults. SEARCH
      STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group
      Specialised Register (December 2005), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library Issue 4, 2005), MEDLINE, EMBASE, the UK National
      Research Register, several orthopaedic journals, conference proceedings and
      reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised
      trials comparing replacement arthroplasty with an internal fixation implant for
      adults with an extracapsular hip fracture. DATA COLLECTION AND ANALYSIS: Both
      review authors independently assessed 10 aspects of trial quality and extracted
      data. We requested additional information from trial investigators. Where
      appropriate, limited pooling of data was performed. MAIN RESULTS: Two randomised
      controlled trials including a total of 148 people aged 70 years or over with
      unstable extracapsular hip fractures in the trochanteric region were identified
      and included in this review. Both had methodological limitations, including
      inadequate assessment of longer-term outcome. One trial compared a cemented
      arthroplasty with a sliding hip screw. This found no significant differences
      between the two methods of treatment for operating time, local wound
      complications, mechanical complications, reoperation, mortality or loss of
      independence of previously independent patients at one year. There was, however,
      a higher blood transfusion need in the arthroplasty group. The other trial
      compared a cementless arthroplasty versus a proximal femoral nail. It also found
      a higher blood transfusion need in the arthroplasty group, together with a
      greater operative blood loss, and a longer length of surgery. There were no
      significant differences between the two interventions for mechanical
      complications, local wound complications, reoperation, general complications,
      mortality at one year or long-term function. None of the pooled outcome data
      yielded statistically significant differences between the arthroplasty and
      internal fixation, with the exception of the significantly higher numbers of
      participants in the arthroplasty group requiring blood transfusion (relative risk
      1.71, 95% confidence interval 1.05 to 2.77). AUTHORS' CONCLUSIONS: There is
      insufficient evidence from randomised trials to determine whether replacement
      arthroplasty has any advantage over internal fixation for extracapsular hip
      fractures. Further larger well-designed randomised trials comparing arthroplasty
      versus internal fixation for the treatment of unstable fractures are required.

PMID- 16625529
TI  - Immunotherapy for recurrent miscarriage.
AB  - BACKGROUND: Because immunological aberrations might be the cause of miscarriage
      in some women, several immunotherapies have been used to treat women with
      otherwise unexplained recurrent pregnancy loss. OBJECTIVES: The objective of this
      review was to assess the effects of any immunotherapy, including paternal
      leukocyte immunization and intravenous immune globulin on the live birth rate in
      women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (December
      2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library
      2004, Issue 3), MEDLINE (1966 to September 2004) and EMBASE (1980 to September
      2004). SELECTION CRITERIA: Randomized trials of immunotherapies used to treat
      women with three or more prior miscarriages and no more than one live birth
      after, in whom all recognised non-immunologic causes of recurrent miscarriage had
      been ruled out and no simultaneous treatment was given. DATA COLLECTION AND
      ANALYSIS: The review author and the two co-authors independently extracted data
      and assessed study quality for all studies considered for this review. MAIN
      RESULTS: Twenty trials of high quality were included. The various forms of
      immunotherapy did not show significant differences between treatment and control
      groups in terms of subsequent live births: paternal cell immunization (12 trials,
      641 women), Peto odds ratio (Peto OR) 1.23, 95% confidence interval (CI) 0.89 to
      1.70; third party donor cell immunization (three trials, 156 women), Peto OR
      1.39, 95% CI 0.68 to 2.82; trophoblast membrane infusion (one trial, 37 women),
      Peto OR 0.40, 95% CI 0.11 to 1.45; intravenous immune globulin, Peto OR 0.98, 95%
      CI 0.61 to 1.58. AUTHORS' CONCLUSIONS: Paternal cell immunization, third party
      donor leukocytes, trophoblast membranes, and intravenous immune globulin provide
      no significant beneficial effect over placebo in improving the live birth rate.

PMID- 16625530
TI  - Pyridoxine (vitamin B6) supplementation in pregnancy.
AB  - BACKGROUND: Vitamin B6 plays vital roles in numerous metabolic processes in the
      human body, such as nervous system development and functioning. It has been
      associated with some benefits in non-randomised studies, such as higher Apgar
      scores, higher birthweights, and reduced incidence of pre-eclampsia and preterm
      birth. Recent studies also suggest a protection against certain congenital
      malformations. OBJECTIVES: To evaluate the clinical effects of vitamin B6
      supplementation during pregnancy and/or labour. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group Trials Register (30 December 2005).
      SELECTION CRITERIA: We included randomised controlled trials comparing vitamin B6
      administration in pregnancy and/or labour with: placebos, no supplementations, or
      supplements not containing vitamin B6. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data and assessed trials for methodological quality. We
      used relative risk and weighted mean difference with 95% confidence intervals.
      MAIN RESULTS: Five trials (1646 women) were included. Four trials used blinding.
      One had adequate method of randomisation and allocation concealment; four did not
      report this. Three trials had large losses to follow up. Vitamin B6 as oral
      capsules or lozenges resulted in decreased risk of dental decay in pregnant women
      (capsules: relative risk (RR) 0.84; 95% confidence interval (CI) 0.71 to 0.98;
      one trial, n = 371; lozenges: RR 0.68; 95% CI 0.56 to 0.83; one trial, n = 342).
      A small trial showed reduced mean birthweights with vitamin B6 supplementation
      (weighted mean difference -0.23 kg; 95% CI -0.42 to -0.04; n = 33; one trial). We
      did not find any statistically significant differences in the risk of eclampsia
      (capsules: n = 1242; three trials; lozenges: n = 944; one trial), pre-eclampsia
      (capsules n = 1197; two trials; lozenges: n = 944; one trial) or low Apgar scores
      at one minute (oral pyridoxine: n = 45; one trial), between supplemented and non
      supplemented groups. No differences were found in Apgar scores at one or five
      minutes, or breastmilk production between controls and women receiving oral (n =
      24; one trial) or intramuscular (n = 24; one trial) loading doses of pyridoxine
      at labour. AUTHORS' CONCLUSIONS: There were few trials, reporting few clinical
      outcomes and mostly with unclear trial methodology and inadequate follow up.
      There is not enough evidence to detect clinical benefits of vitamin B6
      supplementation in pregnancy and/or labour other than one trial suggesting
      protection against dental decay. Future trials assessing this and other outcomes
      such as orofacial clefts, cardiovascular malformations, neurological development,
      preterm birth, pre-eclampsia and adverse events are required.

PMID- 16625531
TI  - Techniques for pelvic surgery in subfertility.
AB  - BACKGROUND: Since the introduction of in-vitro fertilisation (IVF) tubal surgery
      has been less frequently undertaken as a technique to improve fertility in women
      with damaged fallopian tubes. There are various surgical techniques that can be
      used to repair blocked or damaged fallopian tubes. OBJECTIVES: To evaluate the
      role of tubal surgery in the management of tubal infertility and to evaluate
      surgical techniques for the treatment of tubal infertility. SEARCH STRATEGY: This
      review has drawn on the search strategy developed for the Menstrual Disorders and
      Subfertility Group. We identified relevant trials from the Cochrane Menstrual
      Disorders and Subfertility Group Specialised Register (searched up to July 2005)
      and Cochrane Central Register of Controlled Trials (CENTRAL). The following
      databases were searched using the OVID platform: 1. MEDLINE (1966 to July 2005);
      2. EMBASE (1980 to July 2005). SELECTION CRITERIA: All randomised controlled
      trials investigating the following topics on infertility surgery technique as
      follows were included.1) The role of infertility surgery versus no treatment.2)
      The role of infertility surgery versus alternative treatments.3) The role of
      magnification.4) The role of the CO2 laser at infertility surgery. 5) The role of
      operative laparoscopy to perform infertility surgery. 6) Any other intervention
      regarding surgical technique investigated by RCT. DATA COLLECTION AND ANALYSIS:
      Data were extracted independently by the first two authors. Differences of
      opinion were recognised and resolved by consensus. Two by two tables were
      generated for each trial for the dichotomous outcome of pregnancy and the effects
      on pregnancy rate of each study is expressed as an odds ratio with 95% confidence
      intervals. MAIN RESULTS: Seven randomised control trials were identified. No RCTs
      comparing infertility surgery versus no treatment or alternative treatments were
      found. There was no RCT found investigating the use of magnification for tubal
      surgery. There was no evidence for or against the use of a CO2 laser compared
      with standard techniques for adhesiolysis (OR for pregnancy 1.07, 95% CI 0.40 to
      2.87) or salpingostomy (OR for pregnancy 1.38, 95% CI 0.47 to 4.05) from two
      RCTs. One RCT randomised women for salpingostomatolysis by laparotomy and
      laparoscopy using the classic approach or the one suture technique. There was no
      evidence of benefit or disadvantage when laparoscopy was compared to laparotomy.
      The OR for bilateral tubal patency was 1.32 (95% CI 0.55 to 3.22) and unilateral
      tubal patency OR was 0.82 (95% CI 0.29 to 2.29). The pregnancy rate was not
      reported. There was no evidence of benefit or disadvantage from two RCTs
      assessing the use of a prosthesis at salpingostomy compared with non-use
      (combined odds of pregnancy (term) in group using the prosthesis as compared to
      the control (OR for pregnancy at term 1.17, 95% CI 0.47 to 2.93). There was no
      evidence of benefit or disadvantage difference in one RCT comparing Cuff versus
      Bruhat technique for salpingostomy One RCT compared two methods of salpingostomy
      (OR for pregnancy rate ( intrauterine) 1.02, 95% CI 0.22 to 4.61). One RCT showed
      no evidence of benefit or disadvantage for the use of thermocoagulation or
      electrocoagulation at adhesiolysis, odds for pregnancy rate between the two
      groups OR 0.87 (95% CI 0.51 to 1.46). AUTHORS' CONCLUSIONS: From these limited
      data there is no evidence of benefit or disadvantage of tubal surgery versus no
      treatment or alternative treatments. Likewise there is no evidence of advantage
      or disadvantage of using microsurgery over standard techniques; laparoscopic
      approach over laparotomy; the use of CO2 laser; or electrocoagulation over
      thermocoagulation. Randomised controlled trials should be undertaken to determine
      the role of tubal surgery versus no treatment or alternative treatments.
      Randomised controlled trials should be undertaken to determine the role at tubal
      surgery of magnification, laparoscopic approach, the use of lasers or
      electrocoagulation.

PMID- 16625532
TI  - Antioxidant vitamin and mineral supplements for slowing the progression of age
      related macular degeneration.
AB  - BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
      the retina by reacting with free radicals that are produced in the process of
      light absorption. OBJECTIVES: The objective of this review was to assess the
      effects of antioxidant vitamin or mineral supplementation, or both, on the
      progression of age-related macular degeneration (AMD). SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library (2005, Issue 4); MEDLINE (1966 to January 2006); SIGLE (1980 to
      March 2005); EMBASE (1980 to January 2005); NRR (2005, Issue 4); AMED (1985 to
      January 2006); and PubMed (24 January 2006 covering last 60 days), reference
      lists of identified reports and the Science Citation Index. We contacted
      investigators and experts in the field for details of unpublished studies.
      SELECTION CRITERIA: We included randomised trials comparing antioxidant vitamin
      or mineral supplemention (alone or in combination) to a control intervention in
      people with AMD. DATA COLLECTION AND ANALYSIS: The author extracted data and
      assessed trial quality. Where appropriate, data were pooled using a random
      effects model unless three or fewer trials were available in which case a fixed
      effects model was used. MAIN RESULTS: Eight trials were included in this review.
      The majority of people were randomised in one trial (AREDS in the USA) that found
      a beneficial effect of antioxidant (beta-carotene, vitamin C and vitamin E) and
      zinc supplementation on progression to advanced AMD (adjusted odds ratio 0.68,
      99% confidence interval 0.49 to 0.93). People taking supplements were less likely
      to lose 15 or more letters of visual acuity (adjusted odds ratio 0.77, 99%
      confidence interval 0.58 to 1.03). Hospitalisation for genito-urinary problems
      was more common in people taking zinc and yellowing of skin was more common in
      people taking antioxidants. The other trials were, in general, small and the
      results were inconsistent. AUTHORS' CONCLUSIONS: The evidence as to the
      effectiveness of antioxidant vitamin and mineral supplementation in halting the
      progression of AMD comes mainly from one large trial in the USA. The
      generalisability of these findings to other populations with different
      nutritional status is not known. Further large, well-conducted randomised
      controlled trials in other populations are required. Long-term harm from
      supplementation cannot be ruled out. Beta-carotene has been found to increase the
      risk of lung cancer in smokers; vitamin E has been associated with an increased
      risk of heart failure in people with vascular disease or diabetes.

PMID- 16625533
TI  - Audit and feedback: effects on professional practice and health care outcomes.
AB  - BACKGROUND: Audit and feedback continues to be widely used as a strategy to
      improve professional practice. It appears logical that healthcare professionals
      would be prompted to modify their practice if given feedback that their clinical
      practice was inconsistent with that of their peers or accepted guidelines. Yet,
      audit and feedback has not consistently been found to be effective. OBJECTIVES:
      To assess the effects of audit and feedback on the practice of healthcare
      professionals and patient outcomes. SEARCH STRATEGY: We searched the Cochrane
      Effective Practice and Organisation of Care Group's register and pending file up
      to January 2004. SELECTION CRITERIA: Randomised trials of audit and feedback
      (defined as any summary of clinical performance over a specified period of time)
      that reported objectively measured professional practice in a healthcare setting
      or healthcare outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted data and assessed study quality. Quantitative (meta-regression), visual
      and qualitative analyses were undertaken. For each comparison we calculated the
      risk difference (RD) and risk ratio (RR), adjusted for baseline compliance when
      possible, for dichotomous outcomes and the percentage and the percent change
      relative to the control group average after the intervention, adjusted for
      baseline performance when possible, for continuous outcomes. We investigated the
      following factors as possible explanations for the variation in the effectiveness
      of interventions across comparisons: the type of intervention (audit and feedback
      alone, audit and feedback with educational meetings, or multifaceted
      interventions that included audit and feedback), the intensity of the audit and
      feedback, the complexity of the targeted behaviour, the seriousness of the
      outcome, baseline compliance and study quality. MAIN RESULTS: Thirty new studies
      were added to this update, and a total of 118 studies are included. In the
      primary analysis 88 comparisons from 72 studies were included that compared any
      intervention in which audit and feedback is a component compared to no
      intervention. For dichotomous outcomes the adjusted risk difference of compliance
      with desired practice varied from - 0.16 (a 16 % absolute decrease in compliance)
      to 0.70 (a 70% increase in compliance) (median = 0.05, inter-quartile range =
      0.03 to 0.11) and the adjusted risk ratio varied from 0.71 to 18.3 (median =
      1.08, inter-quartile range = 0.99 to 1.30). For continuous outcomes the adjusted
      percent change relative to control varied from -0.10 (a 10 % absolute decrease in
      compliance) to 0.68 (a 68% increase in compliance) (median = 0.16, inter-quartile
      range = 0.05 to 0.37). Low baseline compliance with recommended practice and
      higher intensity of audit and feedback were associated with larger adjusted risk
      ratios (greater effectiveness) across studies. AUTHORS' CONCLUSIONS: Audit and
      feedback can be effective in improving professional practice. When it is
      effective, the effects are generally small to moderate. The relative
      effectiveness of audit and feedback is likely to be greater when baseline
      adherence to recommended practice is low and when feedback is delivered more
      intensively.

PMID- 16625534
TI  - Strategies for detecting colon cancer and/or dysplasia in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Patients with longstanding ulcerative colitis and colonic Crohn's
      disease have an increased risk of colorectal cancer compared with the general
      population. This review assesses the evidence that endoscopic surveillance may
      prolong life by allowing earlier detection of colon cancer or its pre-cursor
      lesion, dysplasia, in patients with inflammatory bowel disease. OBJECTIVES: To
      assess the effectiveness of cancer surveillance programs in reducing the death
      rate from colorectal cancer in patients with ulcerative colitis and colonic
      Crohn's disease. SEARCH STRATEGY: The following strategies were used to identify
      relevant studies:1. MEDLINE and the Cochrane Central Register of Controlled
      Trials were searched from 1966 to August 2005. The medical subject headings
      "Ulcerative Colitis", "Crohn Disease" or "Inflammatory Bowel Disease" and
      "Surveillance" or "Cancer" were used to perform key-word searches of the
      databases.2. Hand searching of reference lists from papers. SELECTION CRITERIA:
      Potentially relevant articles were reviewed independently and unblinded by three
      authors to determine if they fulfilled the selection criteria. Each article was
      rated as being eligible, ineligible, or without sufficient information to
      determine eligibility. Any disagreement between reviewers was resolved by
      consensus. Any trials published in abstract form were only considered if it was
      possible to obtain full details of the protocol and results from the authors.
      DATA COLLECTION AND ANALYSIS: Eligible articles were reviewed in duplicate and
      the results of the primary research trials were abstracted onto specially
      designed data extraction forms. The proportion of patients dying from bowel
      cancer or other causes in the control and surveillance groups of each study was
      derived from life tables, survival curves or where possible, by calculating life
      tables from the data provided. Data from the original research articles were
      converted into 2x2 tables (survival versus death x surveillance versus control)
      for each of the individual studies for comparable follow-up intervals. The
      presence of significant heterogeneity among studies was tested by the chi-square
      test. Because this is a relatively insensitive test, a P value of less than 0.1
      was considered statistically significant. Provided statistical heterogeneity was
      not present, the fixed effects model was used for the pooling of data. The 2x2
      tables were combined into a summary test statistic using the pooled relative risk
      (RR) and 95% confidence intervals as described by Cochrane and Mantel and
      Haenszel. MAIN RESULTS: Karlen 1998a in a nested case-control study comprising
      142 patients from a study population of 4664 UC patients, found that 2/40
      patients dying of colorectal cancer had undergone surveillance colonoscopy on at
      least one occasion compared with 18/102 controls (RR 0.28, 95% CI 0.07 to 1.17).
      One of 40 patients who died from colorectal cancer had undergone surveillance
      colonoscopies on two or more occasions compared with 12/102 controls (RR 0.22,
      95% CI 0.03 to 1.74) in contrast to a more modest effect observed for patients
      who had only one colonoscopy (RR 0.43, 95% CI 0.05 to 3.76). Choi 1993 found that
      carcinoma was detected at a significantly earlier stage in the surveilled
      patients; 15/19 had Duke's A or B carcinoma in the surveilled group compared to
      9/22 in the non-surveilled group (P = 0.039). The 5-year survival rate was 77.2%
      for cancers occurring in the surveillance group and 36.3% for the no-surveillance
      group (P = 0.026). Four of 19 patients in the surveillance group died from
      colorectal cancer compared to 11 of 22 patients in the non-surveillance group (RR
      0.42, 95% CI 0.16 to 1.11). Lashner 1990 found that four of 91 patients in a
      surveillance group died from colorectal cancer compared to 2 of 95 patients in a
      non-surveilled group (RR 2.09, 95% CI 0.39 to 11.12). Colectomy was less common
      in the surveillance group, 33 compared to 51 (P < 0.05) and was performed four
      years later (after 10 years of disease) in the surveillance group. For the pooled
      data analysis 8/110 patients in the surveillance group died from colorectal
      cancer compared to 13/117 patients in the non-surveillance group (RR 0.81, 95% CI
      0.17 to 3.83). AUTHORS' CONCLUSIONS: There is no clear evidence that surveillance
      colonoscopy prolongs survival in patients with extensive colitis. There is
      evidence that cancers tend to be detected at an earlier stage in patients who are
      undergoing surveillance, and these patients have a correspondingly better
      prognosis, but lead-time bias could contribute substantially to this apparent
      benefit. There is indirect evidence that surveillance is likely to be effective
      at reducing the risk of death from IBD-associated colorectal cancer and indirect
      evidence that it may be acceptably cost-effective.

PMID- 16625535
TI  - Piracetam for acute ischaemic stroke.
AB  - BACKGROUND: Piracetam has neuroprotective and antithrombotic effects which may
      help to reduce death and disability in people with acute stroke. OBJECTIVES: The
      objective of this review was to assess the effects of piracetam in acute presumed
      ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched 20 June 2005). In addition, we searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2,
      2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), and ISI Science
      Citation Index (1981 to April 2005). We also contacted the manufacturer of
      piracetam to identify further published and unpublished studies. SELECTION
      CRITERIA: Randomised trials comparing piracetam with control, with at least
      mortality reported and entry to the trial within approximately 48 hours of stroke
      onset. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed
      trial quality and this was checked by the other two authors. Study authors were
      contacted for missing information. MAIN RESULTS: Three trials involving 1002
      people were included, with one trial contributing 93% of the data. Participants'
      ages ranged from 40 to 85, and both sexes were equally represented. Piracetam was
      associated with a statistically non-significant increase in death at one month
      (approximately 31% increase, 95% confidence interval 81% increase to 5%
      reduction). This trend was no longer apparent in the large trial after correction
      for imbalance in stroke severity. Limited data showed no difference between the
      treatment and control groups for functional outcome, dependency or proportion of
      patients dead or dependent. Adverse effects were not reported. AUTHORS'
      CONCLUSIONS: There is some suggestion (but no statistically significant result)
      of an unfavourable effect of piracetam on early death, but this may have been
      caused by baseline differences in stroke severity in the trials. There is not
      enough evidence to assess the effect of piracetam on dependency.

PMID- 16625536
TI  - Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.
AB  - BACKGROUND: The newer 5-ASA preparations were intended to avoid the adverse
      effects of SASP while maintaining its therapeutic benefits. The efficacy and
      safety of 5-ASA preparations have been evaluated in numerous clinical trials that
      have often lacked sufficient statistical power to arrive at definitive
      conclusions. Previously, it was found that newer 5-ASA drugs in doses of at least
      2 g/day, were more effective than placebo but no more effective than SASP in
      inducing remission in ulcerative colitis. This updated review includes more
      recent studies and evaluates the effectiveness, dose-responsiveness, and safety
      of 5-ASA preparations in terms of more precise outcome measures. OBJECTIVES: To
      assess the efficacy, dose-responsiveness and safety of the newer release
      formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or
      sulfasalazine (SASP) for the induction of remission in active ulcerative colitis.
      SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981
      2005) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register,
      the Cochrane IBD/FBD group specialized trials register and the Science Citation
      Index, followed by a manual search of reference lists from previously retrieved
      articles, review articles, symposia proceedings, and abstracts from major
      gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for
      analysis if they were randomized, double-blinded, and controlled clinical trials
      of parallel design, with treatment durations of a minimum of four weeks. DATA
      COLLECTION AND ANALYSIS: Based on an intention to treat principle, the outcomes
      of interest in the treatment of active disease were the failure to induce
      global/clinical remission, global/clinical improvement, endoscopic remission, or
      endoscopic improvement. MAIN RESULTS: 5-ASA was superior to placebo with regard
      to all measured outcome variables. For the failure to induce global/clinical
      improvement or remission, the pooled Peto odds ratio was 0.40 (95% CI, 0.30 to
      0.53). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared
      to SASP, the pooled Peto odds ratio was 0.83 (95% CI 0.60 to 1.13) for the
      failure to induce global/clinical improvement or remission, and 0.66 (95% CI 0.42
      to 1.04) for the failure to induce endoscopic improvement. SASP was not as well
      tolerated as 5-ASA. AUTHORS' CONCLUSIONS: The newer 5-ASA preparations were
      superior to placebo and tended towards therapeutic benefit over SASP. However,
      considering their relative costs, a clinical advantage to using the newer 5-ASA
      preparations in place of SASP appears unlikely. This review updates the existing
      review of oral 5-aminosalicylic acid for induction of remission in ulcerative
      colitis which was published in the Cochrane Library (Issue 1, 2006).

PMID- 16625537
TI  - Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.
AB  - BACKGROUND: The newer 5-ASA preparations were intended to avoid the adverse
      effects of SASP while maintaining its therapeutic benefits. The efficacy and
      safety of 5-ASA preparations have been evaluated in numerous clinical trials that
      have often lacked sufficient statistical power to arrive at definitive
      conclusions. Previously, it was found that newer 5-ASA drugs were more effective
      than placebo but no more effective than SASP in inducing remission in ulcerative
      colitis. This updated review includes more recent studies and evaluates the
      effectiveness, dose-responsiveness, and safety of 5-ASA preparations in terms of
      more precise outcome measures. OBJECTIVES: To assess the efficacy, dose
      responsiveness and safety of the newer release formulations of 5-aminosalicylic
      acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of
      remission in ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature
      search for relevant studies (1981-2005) was performed using MEDLINE, BIOS, the
      Cochrane Controlled Trials Register, the Cochrane IBD/FBD Group Specialized
      Trials Register, and the Science Citation Index, followed by a manual search of
      reference lists from previously retrieved articles, review articles, symposia
      proceedings, and abstracts from major gastrointestinal conferences. SELECTION
      CRITERIA: Studies were accepted for analysis if they were prospective,
      randomized, double-blinded, and placebo- or SASP-controlled clinical trials of
      parallel design with treatment duration of at least six months. DATA COLLECTION
      AND ANALYSIS: Based on an intention to treat principle, the primary outcome was
      the failure to maintain clinical or endoscopic remission. Secondary outcomes were
      the number of patients experiencing adverse events, the number of patients
      withdrawn due to adverse events, and exclusions or withdrawals after entry into
      the study (not due to relapse). All data were analyzed using the Peto odds ratio
      and corresponding 95% confidence intervals (CI). MAIN RESULTS: The Peto odds
      ratio for the failure to maintain clinical or endoscopic remission (withdrawals
      and relapses) for 5-ASA versus placebo was 0.47 (95% CI, 0.36 to 0.62) with an
      NNT of 6. These values were also calculated for the trials in which SASP and 5
      ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a
      negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness
      for SASP.SASP and 5-ASA had similar adverse event profiles, with odds ratios of
      1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were
      determined to be 171 and 78 respectively. AUTHORS' CONCLUSIONS: The newer 5-ASA
      preparations were superior to placebo in maintenance therapy. However, the newer
      preparations had a statistically significant therapeutic inferiority relative to
      SASP. This review updates the existing review of oral 5-aminosalicylic acid for
      maintenance of remission in ulcerative colitis which was published in the
      Cochrane Library (Issue 1, 2006).

PMID- 16625538
TI  - Interventions for preventing oral mucositis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly more effective but is associated
      with short and long-term side effects. Oral side effects remain a major source of
      illness despite the use of a variety of agents to prevent them. One of these side
      effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the
      effectiveness of prophylactic agents for oral mucositis in patients with cancer
      receiving treatment, compared with other potentially active interventions,
      placebo or no treatment. SEARCH STRATEGY: The Cochrane Oral Health Group Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      and EMBASE were searched. Reference lists from relevant articles were scanned and
      the authors of eligible studies were contacted to identify trials and obtain
      additional information. Date of most recent searches: April 2004. SELECTION
      CRITERIA: Trials were selected if they met the following criteria: design -
      random allocation of participants; participants - anyone with cancer receiving
      chemotherapy or radiotherapy treatment for cancer; interventions - agents
      prescribed to prevent oral mucositis; outcomes - prevention of mucositis, pain,
      amount of analgesia, dysphagia, systemic infection, length of hospitalisation,
      cost and patient quality of life. DATA COLLECTION AND ANALYSIS: Information
      regarding methods, participants, interventions and outcome measures and results
      were independently extracted, in duplicate, by two review authors. Authors were
      contacted for details of randomisation and withdrawals and a quality assessment
      was carried out. The Cochrane Oral Health Group statistical guidelines were
      followed and risk ratios (RR) calculated using random-effects models. MAIN
      RESULTS: Two hundred and two studies were eligible. One hundred and thirty two
      were excluded for various reasons, usually as there was no useable information on
      mucositis. Of the 71 useable studies all had data for mucositis comprising 5217
      randomised patients. Interventions evaluated were: acyclovir, allopurinol
      mouthrinse, aloe vera, amifostine, antibiotic pastille or paste, benzydamine,
      beta carotene, calcium phosphate, camomile, chlorhexidine, clarithromycin,
      folinic acid, glutamine, GM-CSF, honey, hydrolytic enzymes, ice chips, iseganan,
      keratinocyte GF, misonidazole, oral care, pentoxifylline, povidone, prednisone,
      propantheline, prostaglandin, sucralfate, traumeel and zinc sulphate. Of the 29
      interventions included in trials, 10 showed some evidence of a benefit (albeit
      sometimes weak) for either preventing or reducing the severity of mucositis.
      Interventions where there was more than one trial in the meta-analysis finding a
      significant difference when compared with a placebo or no treatment were:
      amifostine which provided minimal benefit in preventing moderate and severe
      mucositis RR = 0.84 (95% confidence interval (CI) 0.75 to 0.95) and 0.60 (95% CI
      0.37 to 0.97), antibiotic paste or pastille demonstrated a moderate benefit in
      preventing mucositis RR = 0.87 (95% CI 0.79 to 0.97), hydrolytic enzymes reduced
      moderate and severe mucositis with RRs = 0.52 (95% CI 0.36 to 0.74) and 0.17 (95%
      CI 0.06 to 0.52), and ice chips prevented mucositis at all levels RR = 0.63 (95%
      CI 0.44 to 0.91), 0.43 (95% CI 0.23 to 0.81), 0.27 (95% CI 0.11 to 0.68). Other
      interventions showing some benefit with only one study were: benzydamine, calcium
      phosphate, honey, oral care protocols, povidone and zinc sulphate. The number
      needed to treat (NNT) to prevent one patient experiencing moderate or severe
      mucositis over a baseline incidence of 60% for amifostine is 10 (95% CI 7 to 33),
      antibiotic paste or pastille 13 (95% CI 8 to 56), hydrolytic enzyme 4 (95% CI 3
      to 6) and ice chips 5 (95% CI 3 to 19). When the baseline incidence is 40%/90%
      the NNTs for amifostine are 16/7, for antibiotic paste or pastille 19/7, for
      hydrolytic enzyme 5/3 and for ice chips 7/3. The general reporting of RCTs was
      poor. However, the assessments of the quality of the randomisation improved when
      the authors provided additional information. AUTHORS' CONCLUSIONS: Several of the
      interventions were found to have some benefit at preventing or reducing the
      severity of mucositis associated with cancer treatment. The strength of the
      evidence was variable and implications for practice include consideration that
      benefits may be specific for certain cancer types and treatment. There is a need
      for well designed and conducted trials with sufficient numbers of participants to
      perform subgroup analyses by type of disease and chemotherapeutic agent.

PMID- 16625539
TI  - Amantadine and rimantadine for influenza A in adults.
AB  - BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral
      properties, but they are not widely used due to a lack of knowledge of their
      potential value and concerns about possible adverse effects. OBJECTIVES: The
      objective of this review was to assess the efficacy, effectiveness and safety
      ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE
      (October 2003 to July 2005) and reference lists of articles. SELECTION CRITERIA:
      Randomised and quasi-randomised studies comparing amantadine and/or rimantadine
      with placebo, control medication or no intervention, or comparing doses or
      schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND
      ANALYSIS: For prophylaxis (prevention) trials the numbers of participants with
      clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A
      and adverse effects were analysed. Analysis for treatment trials was of the mean
      duration of fever, length of hospital stay and adverse effects. MAIN RESULTS:
      Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%),
      and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of
      fever by one day (95% CI 0.7 to 1.2). Rimantadine demonstrated comparable
      effectiveness, but there were fewer trials and the results for prophylaxis were
      not statistically significant. Both amantadine and rimantadine induced
      significant gastrointestinal adverse effects. Adverse effects of the central
      nervous system and study withdrawals were significantly more common with
      amantadine than rimantadine. Neither drug affected the rate of viral shedding
      from the nose and the course of asymptomatic influenza. AUTHORS' CONCLUSIONS:
      Amantadine and rimantadine have comparable efficacy and effectiveness in
      relieving or treating symptoms of influenza A in healthy adults, although
      rimantadine induces fewer adverse effects than amantadine. The effectiveness of
      both drugs in interrupting transmission is probably low. Routine use of both
      drugs should be discouraged and both drugs should only be used when all other
      measures fail.

PMID- 16625540
TI  - Antibiotics versus placebo for acute bacterial conjunctivitis.
AB  - BACKGROUND: There are concerns about whether antibiotic therapy confers
      significant clinical benefit in the treatment of acute bacterial conjunctivitis.
      OBJECTIVES: The aim of this review was to assess the benefit and harm of
      antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register),
      MEDLINE, EMBASE, SIGLE, NRR, PubMed and the reference lists of identified trial
      reports. We used the Science Citation Index to look for articles that cited the
      relevant studies, and we contacted investigators and pharmaceutical companies for
      information about additional trials. SELECTION CRITERIA: We included double
      masked randomised controlled trials in which any form of antibiotic treatment had
      been compared with placebo in the management of acute bacterial conjunctivitis.
      This included topical, systemic and combination (for example, antibiotics and
      steroids) antibiotic treatments. DATA COLLECTION AND ANALYSIS: One author
      extracted data and the accuracy was checked by a second author. MAIN RESULTS:
      This review includes five trials which randomised a total of 1034 participants.
      One further trial is currently 'awaiting assessment'. This has been published in
      abstract form and has yet to be fully reported. Three of the trials have been
      conducted on a selected specialist care patient population and the two more
      recent trials have been conducted in a community care setting. The trials were
      heterogeneous in terms of their inclusion and exclusion criteria, the nature of
      the intervention, and the outcome measures assessed. Meta-analyses of data on
      clinical and microbiological remission rates reveal that topical antibiotics are
      of benefit in improving early (days 2 to 5) clinical (RR 1.24, 95% CI 1.05 to
      1.45) and microbiological (RR 1.77, 95% CI 1.23 to 2.54) remission rates; later
      (days 6 to 10) data reveal that these early advantages in clinical (RR 1.11, 95%
      CI 1.02 to 1.21) and microbiological cure rates are reduced (RR 1.56, 95% CI 1.17
      to 2.09), but persist. Most cases however resolve spontaneously with clinical
      remission being achieved in 65% (95% CI 59 to 70) by days 2 to 5 in those
      receiving placebo. No serious outcomes were reported in either the active or
      placebo arms of these trials, indicating that important sight-threatening
      complications are an infrequent occurrence. AUTHORS' CONCLUSIONS: Acute bacterial
      conjunctivitis is frequently a self-limiting condition, but the use of
      antibiotics is associated with significantly improved rates of clinical and
      microbiological remission.

PMID- 16625541
TI  - Fluid and pharmacological agents for adhesion prevention after gynaecological
      surgery.
AB  - BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion
      formation and adhesion reformation. Since subsequent fertility is reduced with
      increasing severity of periadnexal adhesions, pelvic adhesions will remain a
      clinical problem in infertility patients. Steroids, antihistamines and heparin
      were amongst the first substances to be advocated for adhesion prevention. More
      recently icodextrin 4%, hyaluronic acid agents and SprayGel have been used. This
      review aims to evaluate the role of fluid and pharmacological agents in the
      prevention of adhesions in fertility-conserving gynaecological surgery.
      OBJECTIVES: To investigate fluid and pharmacological agents for adhesion
      prevention when used as adjuvants during pelvic surgery. SEARCH STRATEGY: This
      review has drawn on the search strategy developed for the Menstrual Disorders and
      Subfertility Group. The following databases were searched: the Cochrane Menstrual
      Disorders and Subfertility Group Specialised Register, Cochrane Central Register
      of Controlled Trials (CENTRAL), MEDLINE and EMBASE. SELECTION CRITERIA:
      Randomised controlled trials investigating the use of fluid and pharmacological
      agents to prevent adhesion formation after fertility-conserving gynaecological
      surgery. DATA COLLECTION AND ANALYSIS: Data extraction and analysis was performed
      independently by two authors (Metwally M and Watson A). Two-by-two tables were
      generated for dichotomous outcomes and expressed as odds ratios (OR) with 95%
      confidence intervals (CI). For continuous outcomes a standardised mean difference
      was used. MAIN RESULTS: There is no evidence of benefit from the use of steroids,
      dextran or other pharmacological agents in any of the outcomes. The use of
      hyaluronic acid agents may decrease adhesion formation (OR 0.31, 95% CI 0.19 to
      0.51) and prevent the deterioration of pre-existing adhesions (OR 0.28 (95% CI
      0.12 to 0.66). There is insufficient evidence for the use of icodextrin 4% or
      SprayGel as adhesion-preventing agents. None of the studied agents has been shown
      to improve the pregnancy rate when used as an adjunct during pelvic surgery.
      AUTHORS' CONCLUSIONS: The current evidence for the use of fluid and
      pharmacological agents for the prevention of adhesions is limited. There is no
      evidence on any benefit for improving pregnancy outcomes when pharmacological and
      fluid agents are used as an adjunct during pelvic surgery. There is insufficient
      evidence for the use of the following agents: steroids, icodextrin 4%, SprayGel
      and dextran in improving adhesions following surgery. There is some evidence that
      hyaluronic acid agents may decrease the proportion of adhesions and prevent the
      deterioration of pre existing adhesions. However, due to the limited number of
      studies available, this evidence should be interpreted with caution and further
      studies are needed.

PMID- 16625542
TI  - Oral misoprostol for induction of labour.
AB  - BACKGROUND: Misoprostol is a synthetic prostaglandin that can be given orally or
      vaginally. In most countries misoprostol has not been licensed for use in
      pregnancy, but its unlicensed use is common because misoprostol is cheap, stable
      at room temperature and effective in causing uterine contractions. Oral use of
      misoprostol may be convenient, but high doses could cause uterine
      hyperstimulation and uterine rupture which may be life-threatening for both
      mother and fetus. OBJECTIVES: To assess the effectiveness and safety of oral
      misoprostol used for labour induction in women with a viable fetus in the third
      trimester of pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group Trials Register (January 2005). SELECTION CRITERIA: Randomised
      trials comparing oral misoprostol versus other methods, placebo or no treatment,
      given to women with a viable fetus for labour induction. DATA COLLECTION AND
      ANALYSIS: Three authors independently assessed trial quality and extracted data,
      using centrally-designed data sheets. MAIN RESULTS: Forty-one trials (8606
      participants) were included. In four trials comparing oral misoprostol with
      placebo (474 participants), women using oral misoprostol were less likely to have
      long labours (relative risk (RR) 0.16, 95% confidence interval (CI) 0.05 to
      0.49), needed less oxytocin (RR 0.32, 95% CI 0.24 to 0.43) and had a lower
      caesarean section rate (RR 0.62, 95% CI 0.40 to 0.96). In nine trials comparing
      oral misoprostol with vaginal dinoprostone (2627 participants), women given oral
      misoprostol were less likely to need a caesarean section, but this reduction
      reached statistical significance only in the subgroup with intact membranes (RR
      0.78, 95% CI 0.66 to 0.94). Uterine hyperstimulation was more common after oral
      misoprostol (RR 1.63, 95% CI 1.09 to 2.44) although this was not associated with
      any adverse fetal events. Seven trials (1017 participants) compared oral
      misoprostol with intravenous oxytocin. The only difference between the groups was
      an increase in meconium-stained liquor in women with ruptured membranes following
      administration of oral misoprostol (RR 1.72, 95% 1.08 to 2.74). Sixteen trials
      (3645 participants) compared oral and vaginal misoprostol and found no difference
      in the primary outcomes. There was less uterine hyperstimulation without fetal
      heart rate changes in those given oral misoprostol (RR 0.37, 95% 0.23 to 0.59).
      Oral misoprsotol was associated with increased need for oxytocin augmentation (RR
      1.28, 95% 1.11 to 1.48) and more meconium-stained liquor (RR 1.27, 1.01 to 1.60).
      AUTHORS' CONCLUSIONS: Oral misoprostol appears to be more effective than placebo
      and at least as effective as vaginal dinoprostone. However, there remain
      questions about its safety because of a relatively high rate of uterine
      hyperstimulation and the lack of appropriate dose ranging studies. In countries
      where misoprostol remains unlicenced for the induction of labour, many
      practitioners will prefer the legal protection of using a licenced product like
      dinoprostone. There is no evidence that misoprostol given orally is inferior to
      the vaginal route and has lower rates of hyperstimulation. If misoprostol is used
      orally, the dose should not exceed 50 mcg.

PMID- 16625543
TI  - Ipratropium bromide versus short acting beta-2 agonists for stable chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition
      associated with high morbidity, mortality and cost to the community. Patients
      often report symptomatic improvement with short-acting beta-2 agonists (SABA) and
      anticholinergic bronchodilator medications, and both are recommended in COPD
      guidelines. These medications have different mechanisms of action and therefore
      could have an additive effect when combined. OBJECTIVES: To compare the relative
      efficacy and safety of regular long term use (at least four weeks) of ipratropium
      bromide and short- acting beta-2 agonist therapy in patients with stable COPD.
      SEARCH STRATEGY: The Cochrane Airways Group Specialised Register of Trials was
      searched. Bibliographies were checked to identify relevant cross-references. Drug
      companies were contacted for relevant trial data. The searches are current to
      August 2005. SELECTION CRITERIA: All randomised controlled trials comparing at
      least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide)
      alone or in combination with a beta-2 agonist (short acting) versus the beta-2
      agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic
      adult subjects with stable COPD. DATA COLLECTION AND ANALYSIS: Data extraction
      and study quality assessment was performed independently by three reviewers.
      Authors of studies and relevant manufacturers were contacted if data were
      missing. MAIN RESULTS: Eleven studies (3912 participants) met the inclusion
      criteria of the review. Small benefits of ipratropium over a short-acting beta-2
      agonist were demonstrated on lung function outcomes. There were small benefits in
      favour of ipratropium on quality of life (HRQL), as well as a reduction in the
      requirement for oral steroids. Combination therapy with ipratropium plus a short
      acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone
      in terms of post-bronchodilator lung function. There was no significant benefit
      of combination therapy in subjective improvements in HRQL, but again there was a
      reduction in the requirement for oral steroids. AUTHORS' CONCLUSIONS: The
      available data from the trials included in this review suggest that the advantage
      of regular long term use of ipratropium alone or in combination with a short
      acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to
      improve lung function, symptoms and exercise tolerance. Until further data are
      available, the strategy of providing a short-acting beta-2 agonist on a PRN
      basis, and then either continuing with the short-acting beta-2 agonist regularly
      or conducting an "n of 1" trial of regular beta-2 agonist or regular
      anticholinergic to determine the treatment that gives the best relief of symptoms
      (and continuing with it), would seem cost effective. This strategy does need
      formal evaluation. Patient preference is also important, as is the relative
      importance of avoiding the use of systemic corticosteroids.

PMID- 16625544
TI  - Corticosteroids for Guillain-Barre syndrome.
AB  - BACKGROUND: The cause of Guillain-Barre syndrome is inflammation of the
      peripheral nerves, which corticosteroids would be expected to benefit.
      OBJECTIVES: To examine the ability of corticosteroids to hasten recovery and
      reduce the long-term morbidity from Guillain-Barre syndrome. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Register (May 2005), MEDLINE
      (January 2000 to May 2005) and EMBASE (January 1980 to May 2005) and contacted
      trial authors and other experts. SELECTION CRITERIA: We included quasi-randomised
      or randomised controlled trials of people of all ages and all degrees of severity
      of Guillain-Barre syndrome who were treated with any form of corticosteroid or
      adrenocorticotrophic hormone. Our primary outcome measure was change in
      disability grade on a commonly used, validated seven-point scale at four weeks
      after randomisation. Secondary outcome measures were: time from randomisation
      until recovery of unaided walking, time from randomisation until discontinuation
      of ventilation (for those ventilated), mortality, proportion of participants dead
      or disabled (unable to walk without aid) after 12 months, improvement in
      disability grade after six and 12 months, relapse, and adverse events related to
      corticosteroid treatment. DATA COLLECTION AND ANALYSIS: Two authors extracted the
      data. MAIN RESULTS: Six trials with 587 participants provided data for our
      primary outcome measure . The overall evidence showed no significant difference
      between the corticosteroid and non-corticosteroid treated patients in disability
      grade. In four trials of oral corticosteroids with 120 participants in total,
      there was significantly less improvement after four weeks with corticosteroids
      than without corticosteroids (weighted mean difference of 0.82 of a disability
      grade less improvement, 95% confidence intervals 0.17 to 1.47). In two trials
      with a combined total of 467 participants, there was a trend towards more benefit
      from intravenous corticosteroids which was not quite significant, weighted mean
      difference 0.17 (95% confidence intervals -0.06 to 0.39) of a disability grade
      more improvement after four weeks than with placebo. There were no important
      significant differences between the corticosteroid-treated participants and the
      control group in any of the secondary outcome measures. Diabetes was
      significantly more common and hypertension much less common in the corticosteroid
      treated participants. AUTHORS' CONCLUSIONS: Limited evidence shows that oral
      corticosteroids significantly slow recovery from Guillain-Barre syndrome.
      Substantial evidence shows that intravenous methylprednisolone alone does not
      produce significant benefit or harm. In combination with intravenous
      immunoglobulin, intravenous methylprednisolone may hasten recovery but does not
      significantly affect the long-term outcome. More research is needed and more
      effective treatments for Guillain-Barre syndrome should be sought.

PMID- 16625545
TI  - Educational games for mental health professionals.
AB  - BACKGROUND: In traditional didactic teaching, the learner has a passive role,
      digesting the knowledge presented by the teacher. Stimulating and active teaching
      processes may be better at instilling information than more pedestrian
      approaches. Games involving repetition, reinforcement, association and use of
      multiple senses have been proposed as part of experiential learning. OBJECTIVES:
      To assess the effects of educational games on the knowledge and clinical skill of
      mental health professionals compared to the effects of standard teaching
      approaches. SEARCH STRATEGY: We performed electronic searches of AMED (1998 -
      November 2005), British Nursing Index (November 2005), Cochrane Library (Issue 3,
      2005), Cochrane Schizophrenia Group Trials Register (November 2005), CINAHL
      (November 2005) EMBASE (November 2005), Educational Resources Information Centre
      on CSA (1966 - November 2005), MEDLINE (November 2005), PsycINFO (November 2005).
      We also searched references of all selected articles and contacted authors of
      included trials for more information. SELECTION CRITERIA: Randomised controlled
      trials comparing any educational game aiming at increasing knowledge and/or
      skills with a standard educational approach for mental health professionals. DATA
      COLLECTION AND ANALYSIS: We extracted data independently and analysed on an
      intention-to-treat basis. We analysed the individual person data using fixed
      effect Peto Odds Ratio (OR) calculated the 95% confidence intervals (CI). If
      appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was
      estimated. For continuous data, we calculated weighted mean differences. MAIN
      RESULTS: We identified one trial (n=34) of an educational game for mental health
      nursing students of only a few hours follow up. For an outcome we arbitrarily
      defined ('no academically important improvement [a 10% improvement in scores]')
      those allocated to educational games fared considerably better than students in
      the standard education techniques group (OR 0.06 CI 0.01 to 0.27, NNT 3 CI 2 to
      4). On average those in the games group scored six more points than the control
      students on a test of questions relevant to psychosis set to the standard of the
      mental health nursing curriculum of the day (WMD 6 CI 2.63 to 9.37). AUTHORS'
      CONCLUSIONS: Current limited evidence suggests educational games could help
      mental health students gain more points in their tests, especially if they have
      left revision to the last minute. This salient study should be refined and
      repeated.

PMID- 16625546
TI  - Guided tissue regeneration for periodontal infra-bony defects.
AB  - BACKGROUND: Conventional treatment of destructive periodontal (gum) disease
      arrests the disease but does not usually regain the bone support or connective
      tissue lost in the disease process. Guided tissue regeneration (GTR) is a
      surgical procedure that specifically aims to regenerate the periodontal tissues
      when the disease is advanced and could overcome some of the limitations of
      conventional therapy. OBJECTIVES: To assess the efficacy of GTR in the treatment
      of periodontal infra-bony defects measured against conventional surgery (open
      flap debridement (OFD)) and factors affecting outcomes. SEARCH STRATEGY: We
      conducted an electronic search of the Cochrane Oral Health Group Trials Register,
      MEDLINE and EMBASE up to April 2004. Handsearching included Journal of
      Periodontology, Journal of Clinical Periodontology, Journal of Periodontal
      Research and bibliographies of all relevant papers and review articles up to
      April 2004. In addition, we contacted experts/groups/companies involved in
      surgical research to find other trials or unpublished material or to clarify
      ambiguous or missing data and posted requests for data on two periodontal
      electronic discussion groups. SELECTION CRITERIA: Randomised, controlled trials
      (RCTs) of at least 12 months duration comparing guided tissue regeneration (with
      or without graft materials) with open flap debridement for the treatment of
      periodontal infra-bony defects. Furcation involvements and studies specifically
      treating aggressive periodontitis were excluded. DATA COLLECTION AND ANALYSIS:
      Screening of possible studies and data extraction was conducted independently.
      The methodological quality of studies was assessed in duplicate using individual
      components and agreement determined by Kappa scores. Methodological quality was
      used in sensitivity analyses to test the robustness of the conclusions. The
      Cochrane Oral Health Group statistical guidelines were followed and the results
      expressed as mean differences (MD and 95% CI) for continuous outcomes and risk
      ratios (RR and 95% CI) for dichotomous outcomes calculated using random-effects
      models. Any heterogeneity was investigated. The primary outcome measure was
      change in clinical attachment. MAIN RESULTS: The search produced 626 titles, of
      these 596 were clearly not relevant to the review. The full text of 32 studies of
      possible relevance was obtained and 15 studies were excluded. Therefore 17 RCTs
      were included in this review, 16 studies testing GTR alone and two testing
      GTR+bone substitutes (one study had both test treatment arms).No tooth loss was
      reported in any study although these data are incomplete where patient follow up
      was not complete. For attachment level change, the mean difference between GTR
      and OFD was 1.22 mm (95% CI Random Effects: 0.80 to 1.64, chi squared for
      heterogeneity 69.1 (df = 15), P < 0.001, I(2) = 78%) and for GTR + bone
      substitutes was 1.25 mm (95% CI 0.89 to 1.61, chi squared for heterogeneity 0.01
      (df = 1), P = 0.91). GTR showed a significant benefit when comparing the numbers
      of sites failing to gain 2 mm attachment with risk ratio 0.54 (95% CI Random
      Effects: 0.31 to 0.96, chi squared for heterogeneity 8.9 (df = 5), P = 0.11). The
      number needed to treat (NNT) for GTR to achieve one extra site gaining 2 mm or
      more attachment over open flap debridement was therefore 8 (95% CI 5 to 33),
      based on an incidence of 28% of sites in the control group failing to gain 2 mm
      or more of attachment. For baseline incidences in the range of the control groups
      of 3% and 55% the NNTs are 71 and 4. Probing depth reduction was greater for GTR
      than OFD: 1.21 mm (95% CI 0.53 to 1.88, chi squared for heterogeneity 62.9 (df =
      10), P < 0.001, I(2) = 84%) or GTR + bone substitutes, weighted mean difference
      1.24 mm (95% CI 0.89 to 1.59, chi squared for heterogeneity 0.03 (df = 1), P =
      0.85). For gingival recession, a statistically significant difference between GTR
      and open flap debridement controls was evident (mean difference 0.26 mm (95% CI
      Random Effects: 0.08, 0.43, chi squared for heterogeneity 2.7 (df = 8), P =
      0.95), with a greater change in recession from baseline for the control group.
      Regarding hard tissue probing at surgical re-entry, a statistically significant
      greater gain was found for GTR compared with open flap debridement. This amounted
      to a weighted mean difference of 1.39 mm (95% CI 1.08 to 1.71, chi squared for
      heterogeneity 0.85 (df = 2), P = 0.65). For GTR + bone substitutes the difference
      was greater, with mean difference 3.37 mm (95% CI 3.14 to 3.61). Adverse effects
      were generally minor although with an increased treatment time for GTR. Exposure
      of the barrier membrane was frequently reported with a lack of evidence of an
      effect on healing. AUTHORS' CONCLUSIONS: GTR has a greater effect on probing
      measures of periodontal treatment than open flap debridement, including improved
      attachment gain, reduced pocket depth, less increase in gingival recession and
      more gain in hard tissue probing at re-entry surgery. However there is marked
      variability between studies and the clinical relevance of these changes is
      unknown. As a result, it is difficult to draw general conclusions about the
      clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a
      significant improvement over conventional open flap surgery, the factors
      affecting outcomes are unclear from the literature and these might include study
      conduct issues such as bias. Therefore, patients and health professionals need to
      consider the predictability of the technique compared with other methods of
      treatment before making final decisions on use. Since trial reports were often
      incomplete, we recommend that future trials should follow the CONSORT statement
      both in their conduct and reporting. There is therefore little value in future
      research repeating simple, small efficacy studies. The priority should be to
      identify factors associated with improved outcomes as well as investigating
      outcomes relevant to patients. Types of research might include large
      observational studies to generate hypotheses for testing in clinical trials,
      qualitative studies on patient-centred outcomes and trials exploring innovative
      analytic methods such as multilevel modelling. Open flap surgery should remain
      the control comparison in these studies.

PMID- 16625547
TI  - Mechanical devices for urinary incontinence in women.
AB  - BACKGROUND: Incontinence can have a devastating effect on the lives of sufferers
      with significant economic implications. Non-surgical treatments such as pelvic
      floor muscle training and the use of mechanical devices are usually the first
      line of management. The latter more so when a person did not want surgery or when
      considered unfit for surgery. Mechanical devices are inexpensive and do not
      compromise future surgical treatment. OBJECTIVES: To determine the effects of
      mechanical devices in the management of adult female urinary incontinence. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register
      (7 December 2005). The register contains trials identified from MEDLINE, the
      Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL and
      handsearching of journals and conference proceedings. SELECTION CRITERIA: All
      randomised or quasi-randomised controlled trials of mechanical devices in the
      management of adult female urinary incontinence determined either by symptom
      classification or by urodynamic diagnosis. DATA COLLECTION AND ANALYSIS: Three
      reviewers assessed the identified studies for eligibility and methodological
      quality and independently extracted data from the included studies. Data analysis
      was performed using RevMan software (version 4.2). MAIN RESULTS: There were six
      trials involving a total of 286 women. Two small trials compared a mechanical
      device with no treatment and although they suggested that use of a mechanical
      device might be better than no treatment, the evidence for this was inconclusive.
      Five trials compared one mechanical device with another. Quantitative synthesis
      of data from these trials was not possible because different mechanical devices
      were compared in each trial using different outcome measures. Data from the
      individual trials showed no clear difference between devices, but with wide
      confidence intervals. There were no trials comparing a mechanical device with
      another type of treatment. AUTHORS' CONCLUSIONS: The place of mechanical devices
      in the management of urinary incontinence remains in question. Currently there is
      little evidence from controlled trials on which to judge whether their use is
      better than no treatment and a large well-conducted trial is required for
      clarification. There was also insufficient evidence in favour of one device over
      another and no evidence to compare mechanical devices with other forms of
      treatment.

PMID- 16625548
TI  - Developmental care for promoting development and preventing morbidity in preterm
      infants.
AB  - BACKGROUND: Preterm infants experience a range of morbidity related to the
      immaturity of their organ systems and to concurrent disease states. There is
      concern that an unfavourable environment in the neonatal intensive care unit
      (NICU) may compound this morbidity. Modification of the environment could
      minimize the iatrogenic effects. Developmental care is a broad category of
      interventions designed to minimize the stress of the NICU environment. These
      interventions may include elements such as control of external stimuli
      (vestibular, auditory, visual, tactile), clustering of nursery care activities,
      and positioning or swaddling of the preterm infant. Individual strategies have
      also been combined to form programs, such as the 'Newborn Individualized
      Developmental Care and Assessment Program' (NIDCAP) (Als 1986). OBJECTIVES: In
      preterm infants, do developmental care interventions reduce neurodevelopmental
      delay, poor weight gain, length of hospital stay, length of mechanical
      ventilation, physiological stress and other clinically relevant adverse outcomes?
      SEARCH STRATEGY: The Neonatal Review Group search strategy was utilized. Searches
      were made of MEDLINE from 1966 to June, 2005 and of CINAHL, The Cochrane Central
      Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), and
      conference and symposia proceedings in the English language from 1990 to June,
      2005. A search of EMBASE was also made from 2003 to June 2005. A list of all
      relevant articles was sent to two experts in the field to identify any omissions
      or additional unpublished studies. SELECTION CRITERIA: Randomized trials in which
      elements of developmental care are compared to routine nursery care for infants <
      37 weeks gestation and that measured clinically relevant outcomes. Reports were
      in English or a language for which a translator was available. Computerized
      searches were conducted and all potentially relevant titles and abstracts were
      extracted. Retrieved articles were assessed for relevance independently by two
      reviewers, based on predetermined criteria. Articles that met all criteria for
      relevance were assessed for methodological quality based on predetermined
      criteria. Articles judged to have the appropriate quality by both reviewers were
      included in the analysis. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by the two authors. Meta-analyses were conducted for each
      intervention where the same outcome measures and/or instruments were used within
      comparable time points. MAIN RESULTS: This review detected 36 eligible randomized
      controlled trials involving four major groups of developmental care
      interventions, 19 sub-groups and multiple clinical outcomes. In addition, the
      long-term outcomes of a previously included trial were added to the review. The
      results of the review indicate that developmental care interventions demonstrate
      limited benefit to preterm infants with respect to: decreased moderate-severe
      chronic lung disease, decreased incidence of necrotizing enterocolitis and
      improved family outcome. Conversely, an increase in mild lung disease and an
      increase in the length of stay were demonstrated in infants receiving
      developmental care compared to controls. There is also very limited evidence of
      the long-term positive effect of NIDCAP on behavior and movement at 5 years
      corrected age but no effect on cognition. Other individualized developmental care
      interventions have also demonstrated some effect in enhancing neurodevelopmental
      outcome. Although a limited number of other benefits were demonstrated, those
      results were from single studies with small sample sizes. The lack of blinding of
      the assessors was a significant methodological flaw in half of the studies. The
      cost of the interventions and personnel was not considered in any of the studies.
      AUTHORS' CONCLUSIONS: Because of the inclusion of multiple interventions in most
      studies, the determination of the effect of any single intervention is difficult.
      Although there is evidence of limited benefit of developmental care interventions
      overall, and no major harmful effects reported, there were a large number of
      outcomes for which no or conflicting effects were demonstrated. The single trials
      that did show a significant effect of an intervention on a major clinical outcome
      were based on small sample sizes, and the findings were often not supported in
      other small trials. Before a clear direction for practice can be supported,
      evidence demonstrating more consistent effects of developmental care
      interventions on important short- and long-term clinical outcomes is needed. The
      economic impact of the implementation and maintenance of developmental care
      practices should be considered by individual institutions.

PMID- 16625549
TI  - Dipyridamole for preventing stroke and other vascular events in patients with
      vascular disease.
AB  - BACKGROUND: Patients with limited cerebral ischaemia of arterial origin are at
      risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk
      by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22%
      risk-reduction compared with aspirin alone. However, a systematic review of all
      trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration
      showed that, in high-risk patients, there was virtually no difference between the
      aspirin-dipyridamole combination and aspirin alone. OBJECTIVES: To assess the
      efficacy and safety of dipyridamole versus control in the secondary prevention of
      vascular events in patients with vascular disease. SEARCH STRATEGY: We searched
      the Cochrane Stroke Group trials register (searched November 2005), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3,
      2005), MEDLINE (1966 to November 2005) and EMBASE (1980 to November 2005).
      SELECTION CRITERIA: Randomised long-term secondary prevention trials with
      concealed treatment allocation, treatment for more than one month, starting
      within six months after presentation of an arterial vascular disease were
      selected. Treatment consisted of dipyridamole with or without other antiplatelet
      drugs compared with no drug or an antiplatelet drug other than dipyridamole. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion,
      assessed trial quality and extracted data. Data were analysed according to the
      intention-to-treat principle. MAIN RESULTS: Twenty-seven trials were included,
      with 20242 patients, among whom 1399 vascular deaths and 3090 fatal and non-fatal
      vascular events occurred during follow up. Compared with control, dipyridamole
      had no clear effect on vascular death (relative risk (RR) 1.02, 95% confidence
      internal (CI) 0.90 to 1.17). This result was not influenced by the dose of
      dipyridamole or type of presenting vascular disease. In the presence of aspirin,
      dipyridamole appeared to reduce the risk of vascular events compared with control
      (RR 0.90, 95% CI 0.82 to 0.97), due to a single large trial in patients
      presenting with cerebral ischaemia. AUTHORS' CONCLUSIONS: For patients who
      presented with arterial vascular disease, there was no evidence that
      dipyridamole, in the presence or absence of another antiplatelet drug reduced the
      risk of vascular death, though it may reduce the risk of further vascular events.
      However, this benefit was found in only one single large trial and only in
      patients presenting after cerebral ischaemia. There was no evidence that
      dipyridamole alone was more efficacious than aspirin. Further trials comparing
      the effects of the combination of dipyridamole with aspirin versus aspirin alone
      are justified.

PMID- 16625550
TI  - Low protein diets for chronic kidney disease in non diabetic adults.
AB  - BACKGROUND: For more than fifty years, low protein diets have been proposed to
      patients with kidney failure. However, the effects of these diets in preventing
      severe renal failure and the need for maintenance dialysis have not been
      resolved. OBJECTIVES: To determine the efficacy of low protein diets in delaying
      the need to start maintenance dialysis. SEARCH STRATEGY: Cochrane Renal Group
      trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, and
      EMBASE. Congress abstracts (American Society of Nephrology since 1990, European
      Dialysis Transplant Association since 1985, International Society of Nephrology
      since 1987). Direct contacts with investigators. Date of most recent search:
      December 2004. SELECTION CRITERIA: Randomised trials comparing two different
      levels of protein intake in adult patients suffering from moderate to severe
      renal failure, followed for at least one year. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently selected studies and extracted data. Statistical analyses
      were performed using the random effects model and the results expressed as
      relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI).
      Collection of the number of "renal deaths" defined as the need for starting
      dialysis, the death of a patient or a kidney transplant during the trial. MAIN
      RESULTS: Eight trials were identified from over 40 studies. A total of 1524
      patients were analysed, 763 had received reduced protein intake and 761 a higher
      protein intake. Two hundred and fifty one renal deaths were recorded, 103 in the
      low protein diet and 148 in the higher protein diet group (RR 0.69, 95% CI 0.56
      to 0.86, P = 0.0007). To avoid one renal death, 2 to 56 patients need to be
      treated with a low protein diet during one year. AUTHORS' CONCLUSIONS: Reducing
      protein intake in patients with chronic kidney disease reduces the occurrence of
      renal death by 31% as compared with higher or unrestricted protein intake. The
      optimal level of protein intake cannot be confirmed from these studies.

PMID- 16625551
TI  - Interventions for ear discharge associated with grommets (ventilation tubes).
AB  - BACKGROUND: The insertion of grommets (also known as ventilation or tympanostomy
      tubes) is one of the most common surgical procedures performed on children.
      Postoperative otorrhoea (discharge) is the most common complication with a
      reported incidence ranging from 10% to 50%. In the UK, many ENT surgeons treat
      with topical antibiotics/steroid combinations, but general practitioners, mainly
      through fears of ototoxicity, are unlikely to prescribe these and choose systemic
      broad-spectrum antibiotics. OBJECTIVES: 1. To identify the most effective non
      surgical management of discharge from ears with grommets in place.2. To identify
      the risks of non-surgical management for this condition (e.g. ototoxicity), and
      to set benefits of treatment against these risks. SEARCH STRATEGY: We searched
      the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,
      Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1974 to 2005). We also
      searched the CINAHL, AMED, LILACS, ISI WEB OF KNOWLEDGE, ISI PROCEEDINGS, mRCT,
      NNR, ZETOC, KOREAMED, CSA, MEDCARIB, INDMED and SAMED databases. The date of the
      last search was February 2005. SELECTION CRITERIA: Randomised controlled trials
      of adults or children, with any type of grommet and an ear with discharge were
      included. The trials compared treatment with placebo or one treatment with
      another. The primary outcome measure was the duration of the discharge. DATA
      COLLECTION AND ANALYSIS: The trials were selected independently according to the
      above criteria by the four reviewers. Differences in opinion over the inclusion
      of studies were resolved by discussion. The studies were graded using the CASP
      critical appraisal tool. Analyses were based on the presence of discharge seven
      days from the onset of treatment. MAIN RESULTS: There was very little good
      quality evidence. Four studies were included, all of them investigating different
      interventions and therefore a meta-analysis was not possible. Only one study
      demonstrated a significant difference. Oral amoxicillin clavulanate was compared
      to placebo in 79 patients. The odds of having a discharge persisting eight days
      after starting treatment was 0.19 (95% CI 0.07 to 0.49) . The number needed to
      treat to achieve that benefit is 2.5. Participants in both arms of this study
      also received daily aural toilet. The results will therefore not be applicable to
      most settings including primary care. No significant benefit was shown in the two
      studies investigating steroids (oral prednisolone with oral amoxicillin
      clavulanate and topical dexamethasone with topical ciprofloxacin ear drops), or
      the one study comparing an antibiotic-steroid combination (Otosporin(R)) drops
      versus spray (Otomize(R)) (although more patients preferred the spray form).
      AUTHORS' CONCLUSIONS: The authors of this review have been unable to identify the
      most effective intervention or to assess the associated risks. Research is
      urgently needed into the effectiveness of oral versus topical antibiotics in this
      group of patients. Clinicians considering antibiotic treatment need to balance
      any potential benefit against the risks of side effects and antibiotic
      resistance.

PMID- 16625552
TI  - Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
AB  - BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free
      treatment. It may also represent the end point of long-term opioid replacement
      treatment such as methadone maintenance. The availability of managed withdrawal
      is essential to an effective treatment system. OBJECTIVES: To assess the
      effectiveness of interventions involving the administration of opioid antagonists
      to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in
      terms of withdrawal signs and symptoms, completion of treatment and adverse
      effects. SEARCH STRATEGY: We searched the Drugs and Alcohol Group register
      (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 4, 2004), Medline (January 1966 to January 2005), Embase (January
      1985 to January 2005), PsycINFO (1967 to January 2005), and Cinahl (1982 to
      December 2004) and reference lists of studies. SELECTION CRITERIA: Controlled
      trials comparing antagonist-induced withdrawal under heavy sedation or
      anaesthesia with another form of treatment, or a different regime of anaesthesia
      based antagonist-induced withdrawal. DATA COLLECTION AND ANALYSIS: One reviewer
      assessed studies for inclusion and undertook data extraction and assessed
      quality. Inclusion decisions and the overall process were confirmed by
      consultation between all three reviewers. MAIN RESULTS: Six studies (five
      randomised controlled trials) involving 834 participants met the inclusion
      criteria for the review.Antagonist-induced withdrawal is more intense but less
      prolonged than withdrawal managed with reducing doses of methadone, and doses of
      naltrexone sufficient for blockade of opioid effects can be established
      significantly more quickly with antagonist-induced withdrawal than withdrawal
      managed with clonidine and symptomatic medications. The level of sedation does
      not affect the intensity and duration of withdrawal, although the duration of
      anaesthesia may influence withdrawal severity. There is a significantly greater
      risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI
      1.13 to 9.12, P = 0.03) and probably also other forms of detoxification. AUTHORS'
      CONCLUSIONS: Heavy sedation compared to light sedation does not confer additional
      benefits in terms of less severe withdrawal or increased rates of commencement on
      naltrexone maintenance treatment. Given that the adverse events are potentially
      life-threatening, the value of antagonist-induced withdrawal under heavy sedation
      or anaesthesia is not supported. The high cost of anaesthesia-based approaches,
      both in monetary terms and use of scarce intensive care resources, suggest that
      this form of treatment should not be pursued.

PMID- 16625553
TI  - Buprenorphine for the management of opioid withdrawal.
AB  - BACKGROUND: Managed withdrawal is a necessary step prior to drug-free treatment.
      It may also represent the end point of maintenance treatment. OBJECTIVES: To
      assess the effectiveness of interventions involving the use of buprenorphine to
      manage opioid withdrawal, for withdrawal signs and symptoms, completion of
      withdrawal and adverse effects. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, including the Cochrane Drugs
      and Alcohol Group trials register, Issue 3, 2005), MEDLINE (January 1966 to
      August 2005), EMBASE (January 1985 to August 2005), PsycINFO (1967 to August
      2005), CINAHL(1982 to July 2005) and reference lists of articles. SELECTION
      CRITERIA: Experimental interventions involved the use of buprenorphine to modify
      the signs and symptoms of withdrawal in participants who were primarily opioid
      dependent. Comparison interventions involved reducing doses of methadone, alpha2
      adrenergic agonists, symptomatic medications or placebo, or different
      buprenorphine-based regimes. DATA COLLECTION AND ANALYSIS: One reviewer assessed
      studies for inclusion and methodological quality, and undertook data extraction.
      Inclusion decisions and the overall process was confirmed by consultation between
      all three reviewers. MAIN RESULTS: Eighteen studies (14 randomised controlled
      trials), involving 1356 participants, were included. Ten studies compared
      buprenorphine with clonidine; four compared buprenorphine with methadone; one
      compared buprenorphine with oxazepam; three compared different rates of
      buprenorphine dose reduction; two compared different starting doses of
      buprenorphine. (Two studies included more than one comparison.)Relative to
      clonidine, buprenorphine is more effective in ameliorating the symptoms of
      withdrawal, patients treated with buprenorphine stay in treatment for longer,
      particularly in an outpatient setting (SMD 0.82, 95% CI 0.57 to 1.06, P < 0.001),
      and are more likely to complete withdrawal treatment (RR 1.73, 95% CI 1.21 to
      2.47, P = 0.003). At the same time there is no significant difference in the
      incidence of adverse effects, but drop-out due to adverse effects may be more
      likely with clonidine. Severity of withdrawal is similar for withdrawal managed
      with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms
      may resolve more quickly with buprenorphine. There is a trend towards completion
      of withdrawal treatment being more likely with buprenorphine relative to
      methadone (RR 1.30, 95% CI 0.97 to 1.73, P = 0.08). AUTHORS' CONCLUSIONS:
      Buprenorphine is more effective than clonidine for the management of opioid
      withdrawal. There appears to be no significant difference between buprenorphine
      and methadone in terms of completion of treatment, but withdrawal symptoms may
      resolve more quickly with buprenorphine.

PMID- 16625554
TI  - Eradication of Helicobacter pylori for non-ulcer dyspepsia.
AB  - BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer
      disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES:
      To determine the effect of H pylori eradication on dyspepsia symptoms in patients
      with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through
      electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE,
      EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords,
      searching bibliographies of retrieved articles, and through contacts with experts
      in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA:
      All parallel group randomised controlled trials (RCTs) comparing drugs to
      eradicate H pylori with placebo or other drugs known not to eradicate H pylori
      for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were
      collected on individual and global dyspeptic symptom scores, quality of life
      measures and adverse effects. Dyspepsia outcomes were dichotomised into
      minimal/resolved versus same/worse symptoms. MAIN RESULTS: Twenty one randomised
      controlled trials were included in the systematic review. Eighteen trials
      compared antisecretory dual or triple therapy with placebo antibiotics +/-
      antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these
      trials gave results as dichotomous outcomes evaluating 3566 patients and there
      was no significant heterogeneity between the studies. There was a 10% relative
      risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to
      placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI =
      10 to 25). A further three trials compared Bismuth based H pylori eradication
      with an alternative pharmacological agent. These trials were smaller and had a
      shorter follow-up but suggested H pylori eradication was more effective than
      either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia.
      AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically
      significant effect in H pylori positive non-ulcer dyspepsia. An economic model
      suggests this modest benefit may still be cost-effective but more research is
      needed.

PMID- 16625555
TI  - Management of faecal incontinence and constipation in adults with central
      neurological diseases.
AB  - BACKGROUND: People with neurological disease have a much higher risk of both
      faecal incontinence and constipation than the general population. There is often
      a fine line between the two conditions, with any management intended to
      ameliorate one risking precipitating the other. Bowel problems are observed to be
      the cause of much anxiety and may reduce quality of life in these people. Current
      bowel management is largely empirical with a limited research base. OBJECTIVES:
      To determine the effects of management strategies for faecal incontinence and
      constipation in people with neurological diseases affecting the central nervous
      system. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised
      Trials Register (searched 26 January 2005), the Cochrane Central Register of
      Controlled Trials (Issue 2, 2005), MEDLINE (January 1966 to May 2005), EMBASE
      (January 1998 to May 2005) and all reference lists of relevant articles.
      SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating any
      types of conservative or surgical measure for the management of faecal
      incontinence and constipation in people with neurological diseases were selected.
      Specific therapies for the treatment of neurological diseases that indirectly
      affect bowel dysfunction were also considered. DATA COLLECTION AND ANALYSIS: Two
      reviewers assessed the methodological quality of eligible trials and two
      reviewers independently extracted data from included trials using a range of pre
      specified outcome measures. MAIN RESULTS: Ten trials were identified by the
      search strategy, most were small and of poor quality. Oral medications for
      constipation were the subject of four trials. Cisapride does not seem to have
      clinically useful effects in people with spinal cord injuries (three trials).
      Psyllium was associated with increased stool frequency in people with Parkinson's
      disease but did not alter colonic transit time (one trial). Prucalopride, an
      enterokinetic did not demonstrate obvious benefits in this patient group (one
      study). Some rectal preparations to initiate defaecation produced faster results
      than others (one trial). Different time schedules for administration of rectal
      medication may produce different bowel responses (one trial). Mechanical
      evacuation may be more effective than oral or rectal medication (one trial).
      There appears to be a benefit to patients in one-off educational interventions
      from nurses. The clinical significance of any of these results is difficult to
      interpret. AUTHORS' CONCLUSIONS: There is still remarkably little research on
      this common and, to patients, very significant condition. It is not possible to
      draw any recommendation for bowel care in people with neurological diseases from
      the trials included in this review. Bowel management for these people must remain
      empirical until well-designed controlled trials with adequate numbers and
      clinically relevant outcome measures become available.

PMID- 16625556
TI  - S-adenosyl-L-methionine for alcoholic liver diseases.
AB  - BACKGROUND: Alcohol is a major cause of liver disease and disrupts methionine and
      oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for
      methylation reactions and participates in the synthesis of glutathione, the main
      cellular antioxidant. Randomised clinical trials have addressed the question
      whether SAMe may benefit patients with alcoholic liver diseases. OBJECTIVES: To
      evaluate the beneficial and harmful effects of SAMe for patients with alcoholic
      liver diseases. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register (May 2005), The Cochrane Central Register of
      Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May
      2005), EMBASE (1980 to May 2005), and Science Citation Index Expanded (searched
      May 2005). SELECTION CRITERIA: We included randomised clinical trials studying
      patients with alcoholic liver diseases. Interventions encompassed per oral or
      parenteral administration of SAMe at any dose versus placebo or no intervention.
      DATA COLLECTION AND ANALYSIS: We performed all analyses according to the
      intention-to-treat method using RevMan Analyses provided by the Cochrane
      Collaboration. We evaluated the methodological quality of the randomised clinical
      trials by quality components. MAIN RESULTS: We identified nine randomised
      clinical trials including a heterogeneous sample of 434 patients with alcoholic
      liver diseases. The methodological quality regarding randomisation was generally
      low, but 8 out of 9 trials were placebo controlled. Only one trial including 123
      patients with alcoholic cirrhosis used adequate methodology and reported clearly
      on all-cause mortality and liver transplantation. We found no significant effects
      of SAMe on all-cause mortality (relative risks (RR) 0.62, 95% confidence interval
      (CI) 0.30 to 1.26), liver-related mortality (RR 0.68, 95% CI 0.31 to 1.48), all
      cause mortality or liver transplantation (RR 0.55; 95% CI 0.27 to 1.09), or
      complications (RR 1.35, 95% CI 0.84 to 2.16), but the analysis is based mostly on
      one trial only. SAMe was not significantly associated with non-serious adverse
      events (RR 4.92; 95% CI 0.59 to 40.89) and no serious adverse events were
      reported. AUTHORS' CONCLUSIONS: We could not find evidence supporting or refuting
      the use of SAMe for patients with alcoholic liver diseases. We need more long
      term, high-quality randomised trials on SAMe for these patients before SAMe may
      be recommended for clinical practice.

PMID- 16625557
TI  - Behavioural and cognitive interventions with or without other treatments for the
      management of faecal incontinence in children.
AB  - BACKGROUND: Faecal incontinence is a common and potentially distressing disorder
      of childhood. OBJECTIVES: To assess the effects of behavioural and/or cognitive
      interventions for the management of faecal incontinence in children. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register
      (searched 1 February 2006). SELECTION CRITERIA: Randomised and quasi-randomised
      trials of behavioural and/or cognitive interventions with or without other
      treatments for the management of faecal incontinence in children. DATA COLLECTION
      AND ANALYSIS: Reviewers selected studies from the literature, assessed study
      quality, and extracted data. Data were combined in a meta-analysis when
      appropriate. MAIN RESULTS: Eighteen randomised trials with a total of 1168
      children met the inclusion criteria. Sample sizes were generally small. All
      studies but one investigated children with functional faecal incontinence.
      Interventions varied amongst trials and few outcomes were shared by trials
      addressing the same comparisons. Combined results of nine trials showed higher
      rather than lower rates of persisting symptoms of faecal incontinence up to 12
      months when biofeedback was added to conventional treatment (OR 1.11 CI 95% 0.78
      to 1.58). This result was consistent with that of two trials with longer follow
      up (OR 1.31 CI 95% 0.80 to 2.15). In one trial the adjunct of anorectal manometry
      to conventional treatment did not result in higher success rates in chronically
      constipated children (OR 1.40 95% CI 0.72 to 2.73 at 24 months). In one small
      trial the adjunct of behaviour modification to laxative therapy was associated
      with a significant reduction in children's soiling episodes at both the three
      month (OR 0.14 CI 95% 0.04 to 0.51) and the 12 month assessment (OR 0.20 CI 95%
      0.06 to 0.65). AUTHORS' CONCLUSIONS: There is no evidence that biofeedback
      training adds any benefit to conventional treatment in the management of
      functional faecal incontinence in children. There was not enough evidence on
      which to assess the effects of biofeedback for the management of organic faecal
      incontinence. There is some evidence that behavioural interventions plus laxative
      therapy, rather than laxative therapy alone, improves continence in children with
      functional faecal incontinence associated with constipation.

PMID- 16625558
TI  - Cyclophosphamide versus methylprednisolone for treating neuropsychiatric
      involvement in systemic lupus erythematosus.
AB  - BACKGROUND: Neuropsychiatric involvement in systemic lupus erythematosus is
      complex and several clinical presentations are related to this disease such as:
      convulsions, chronic headache, transverse myelitis, vascular brain disease,
      psychosis and neural cognitive dysfunction. This systematic review is an update
      of a review performed in 2000. OBJECTIVES: To assess the efficacy and safety of
      cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric
      manifestations of systemic lupus erythematosus. SEARCH STRATEGY: We searched
      EMBASE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and
      MEDLINE up to and including May 2005. Additional articles were sought through
      handsearching in relevant journals. There were no language restrictions.
      SELECTION CRITERIA: All randomised controlled trials that compared
      cyclophosphamide to methylprednisolone were included. Patients of any age and
      gender were included as long as they fulfilled the criterion of the American
      College of Rheumatology for the diagnosis of systemic lupus erythematosus and
      presented with any one of the following neuropsychiatric events: convulsions,
      organic brain syndrome and cranial neuropathy. Outcome measures included the
      following: a) overall mortality (primary event); b) motor and psychiatric deficit
      (primary event); c) clinical improvement (secondary event). DATA COLLECTION AND
      ANALYSIS: Data was independently extracted by two reviewers and cross-checked.
      The methodological quality of each trial was assessed by the same two reviewers.
      Details of the randomisation (generation and concealment), blinding, and the
      number of patients lost to follow-up were recorded. Dichotomous data was
      presented as relative risks with corresponding 95% confidence intervals and a
      clinical relevance table was produced. MAIN RESULTS: We found one randomised
      controlled trial of 32 patients comparing cyclophosphamide versus
      methylprednisolone for the treatment of neuropsychiatric involvement in the
      systemic lupus erythematosus. A significantly greater number of people responded
      to treatment in the cyclophosphamide group. Treatment response was found in 94.7%
      (18/19) of patients using cyclophosphamide compared with 46.2% (6/13) in the
      methylprednisolone group at 24 months (RR 2.05, 95% CI 1.13, 3.73) The NNT for
      response to treatment is 2. Cyclophosphamide use was associated with a reduction
      in prednisone requirements. A significant decrease in the number seizures per
      month was observed in the cyclophosphamide group. All the patients in the
      cyclophosphamide group had electroencephalographic improvement. No significant
      differences in adverse effects between the groups were found. It was not possible
      to extract more data from the study because there was a small number of patients
      in the others clinical subgroups of neurological manifestations and the authors
      did not provide sufficient information for data extraction. AUTHORS' CONCLUSIONS:
      This systematic review found one randomised controlled trial with a small number
      of patients in the different clinical subgroups of neurological manifestation. It
      seems that cyclophosphamide is more effective in the treatment of
      neuropsychiatric involvement in systemic erythematosus lupus compared with
      methylprednisolone. However, properly designed randomised controlled trials that
      involve large, representative numbers of individuals, with explicit clinical and
      laboratory diagnosis criteria, sufficient duration of follow-up and description
      of all relevant outcome measures are necessary to guide practice.

PMID- 16625559
TI  - Intravenous immunoglobulin for myasthenia gravis.
AB  - BACKGROUND: Myasthenia gravis is an autoimmune disease in which autoantibodies
      interfere with neuromuscular transmission. As with other autoimmune diseases,
      people with myasthenia gravis would be expected to benefit from intravenous
      immunoglobulin. OBJECTIVES: The objective of this review was to examine the
      efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia
      gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the
      Cochrane Neuromuscular Disease Group trials register (March 2005) and MEDLINE
      (January 1966 to March 2005) using 'myasthenia gravis' and 'intravenous
      immunoglobulin' as the search terms. SELECTION CRITERIA: We included all
      randomised or quasi-randomised trials in which intravenous immunoglobulin was
      compared with no treatment, placebo or plasma exchange, in people with myasthenia
      gravis. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two
      others checked these data and the source from which they were derived. For
      methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We
      identified five randomised controlled trials, all of which investigated short
      term benefit. The first study of 87 participants with exacerbation found no
      statistically significant difference between immunoglobulin and plasma exchange
      after two weeks. The second study of 12 participants with moderate or severe
      myasthenia gravis treated in a crossover design trial found no statistically
      significant difference in the efficacy of immunoglobulin and plasma exchange
      after four weeks. The third study with 15 participants with mild or moderate
      myasthenia gravis found no statistically significant difference in efficacy of
      intravenous immunoglobulin and placebo after six weeks. The fourth study
      terminated early. It included 33 participants with moderate exacerbations of
      myasthenia gravis and showed no statistically significant difference in the
      efficacy of intravenous immunoglobulin and methylprednisolone. The fifth trial
      including 173 people with myasthenia gravis exacerbations, showed no superiority
      of intravenous immunoglobulin 1 g/kg on two consecutive days over intravenous
      immunoglobulin 1 g/kg on a single day. AUTHORS' CONCLUSIONS: In severe
      exacerbations of myasthenia gravis, one randomised controlled trial did not show
      a significant difference between intravenous immunoglobulin and plasma exchange.
      Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of
      intravenous immunoglobulin. A further trial showed no significant difference
      between intravenous immunoglobulin and oral methylprednisolone. In chronic
      myasthenia gravis, there is insufficient evidence from randomised trials to
      determine whether intravenous immunoglobulin is efficacious. More research is
      needed to determine whether intravenous immunoglobulin reduces the need for
      steroids as suggested by two case series.

PMID- 16625560
TI  - Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting.
AB  - BACKGROUND: There have been recent advances in chemotherapy-induced nausea and
      vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still
      experience these symptoms, and expert panels encourage additional methods to
      reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness
      of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea
      and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE,
      PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials
      Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain,
      Palliative Care and Supportive Care Specialized Register, Cochrane Cancer
      Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized
      trials of acupuncture-point stimulation by any method (needles, electrical
      stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea
      or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by
      investigators of the original trials and pooled using a fixed effect model.
      Relative risks were calculated on dichotomous data. Standardized mean differences
      were calculated for nausea severity. Weighted mean differences were calculated
      for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were
      pooled. Overall, acupuncture-point stimulation of all methods combined reduced
      the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99;
      P = 0.04), but not acute or delayed nausea severity compared to control. By
      modality, stimulation with needles reduced proportion of acute vomiting (RR =
      0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea
      severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76;
      95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not;
      delayed symptoms for acupuncture were not reported. Acupressure reduced mean
      acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P =
      0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation
      showed no benefit for any outcome. All trials used concomitant pharmacologic
      antiemetics, and all, except electroacupuncture trials, used state-of-the-art
      antiemetics. AUTHORS' CONCLUSIONS: This review complements data on post-operative
      nausea and vomiting suggesting a biologic effect of acupuncture-point
      stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced
      acute vomiting, but studies combining electroacupuncture with state-of-the-art
      antiemetics and in patients with refractory symptoms are needed to determine
      clinical relevance. Self-administered acupressure appears to have a protective
      effect for acute nausea and can readily be taught to patients though studies did
      not involve placebo control. Noninvasive electrostimulation appears unlikely to
      have a clinically relevant impact when patients are given state-of-the-art
      pharmacologic antiemetic therapy.

PMID- 16625561
TI  - Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated
      peripheral neuropathies.
AB  - BACKGROUND: Serum monoclonal anti-myelin associated glycoprotein antibodies may
      be pathogenic in some people with IgM paraprotein and demyelinating neuropathy.
      Immunotherapies aimed at reducing the level of these antibodies might be expected
      to be beneficial. OBJECTIVES: To examine the efficacy of any form of
      immunotherapy in reducing disability and impairment resulting from IgM anti
      myelin associated glycoprotein paraprotein-associated demyelinating peripheral
      neuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January
      1980 to March 2005) for controlled trials. We also checked bibliographies and
      contacted authors and experts in the field. SELECTION CRITERIA: We included
      randomised or quasi-randomised controlled trials of participants of any age
      treated with any type of immunotherapy for anti-myelin-associated glycoprotein
      antibody associated demyelinating peripheral neuropathy with monoclonal
      gammopathy of undetermined significance of any severity. Our primary outcome
      measure was change in the Neuropathy Impairment Scale or Modified Rankin Scale at
      six months after randomisationSecondary outcome measures were: Neuropathy
      Impairment Scale or the Modified Rankin Score at 12 months after randomisation;
      ten-metre walk time, subjective clinical scores and electrophysiological
      parameters at six and 12 months after randomisation; IgM paraprotein levels and
      anti-myelin associated glycoprotein antibody titres at six months after
      randomisation and adverse effects of treatments. DATA COLLECTION AND ANALYSIS: We
      identified eight possible trials. Of these, five randomised controlled trials
      were included after discussion between the authors. One author extracted and the
      other checked the data. No missing data could be obtained from trial authors.
      MAIN RESULTS: The five eligible trials (97 participants) tested intravenous
      immunoglobulin, interferon-alpha or plasma exchange. Only two, of intravenous
      immunoglobulin, had comparable interventions and outcomes but both were short
      term. There were no significant benefits of the treatments used in the outcomes
      predefined for this review, but not all the predefined outcomes were used in
      every included trial. Intravenous immunoglobulin showed benefits in terms of
      improvement in Modified Rankin Scale at two weeks and 10-metre walk time at four
      weeks. Serious adverse effects of intravenous immunoglobulin are known to occur
      from observational studies but none were encountered in these trials. AUTHORS'
      CONCLUSIONS: There is inadequate reliable evidence from trials of immunotherapies
      in anti-myelin associated glycoprotein paraproteinaemic neuropathy to recommend
      any particular immunotherapy treatment. Intravenous immunoglobulin is relatively
      safe and may produce some short-term benefit. Large well-designed randomised
      trials of at least six to 12 months duration are required to assess existing or
      novel therapies.

PMID- 16625562
TI  - Perazine for schizophrenia.
AB  - BACKGROUND: Perazine is an old phenothiazine derivative used for the treatment of
      people with schizophrenia and is reputed to have a low level of extrapyramidal
      adverse effects. As far as we are aware, its use is limited to Germany, Poland,
      the former Yugoslavia and the Netherlands. OBJECTIVES: To examine the effects of
      perazine for those with schizophrenia, and schizophrenia-like psychoses. SEARCH
      STRATEGY: We searched the Cochrane Schizophrenia Group's register which includes
      relevant randomised controlled trials from the bibliographic databases Biological
      Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS,
      PSYNDEX, Sociological Abstracts and Sociofile (last update of the review March
      2005). We searched references of all included studies for further trials. We
      contacted pharmaceutical companies and authors of trials. SELECTION CRITERIA: We
      selected all randomised controlled trials that compared perazine with other
      treatments for people with schizophrenia and/or schizophrenia-like psychoses.
      DATA COLLECTION AND ANALYSIS: We independently (SL, BH) inspected citations and
      where possible abstracts and ordered papers for re-inspection and quality
      assessment. We independently extracted data. We excluded data if loss to follow
      up was greater than 50%. For homogeneous dichotomous data we calculated the
      Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the
      number needed to treat (NNT) on an intention-to-treat basis. For continuous data,
      we calculated weighted mean differences (WMD). We inspected all data for
      heterogeneity. MAIN RESULTS: We included six trials with a total of 288
      participants. In only one trial with 95 participants, perazine appeared superior
      to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important
      global improvement' (n=95, RR 0.43 CI 0.2 to 0.8, NNT 4 CI 2 to 13), but there
      was no statistically significant difference in most measures of mental state.
      Perazine did not induce more general adverse events than placebo, but more
      participants received at least one dose of antiparkinson medication (n=95, RR
      4.50 CI 1.0 to 19.5, NNH 6 CI 4 to 33). Five small trials comparing perazine with
      other antipsychotics, including in total only 193 participants, were incompletely
      reported and the outcomes were presented in various ways so that meta-analysis
      was not possible in most occasions. A similar number of participants receiving
      perazine or comparator antipsychotics left the studies early (n=193, RR 0.85, CI
      0.5 to 1.4). The results on efficacy were controversial and need further
      assessment by randomised controlled trials. No obvious differences in adverse
      events between perazine and other antipsychotics could be derived from the
      limited data. Two haloperidol comparisons did not present extrapyramidal side
      effects in a suitable way for use in meta-analysis, but three small comparisons
      with the atypical antipsychotics zotepine and amisulpride showed no higher risk
      of akathisia (n=111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n=111, RR 0.47 CI 0.1 to
      3.5), parkinsonism (n=81, RR 1.21 CI 0.5 2.8) or tremor (n=40, RR 0.80 CI 0.3 to
      2.6) with perazine. AUTHORS' CONCLUSIONS: The number, size and reporting of
      randomised controlled perazine trials is insufficient to present firm conclusions
      about the properties of this antipsychotic. It is possible that perazine is
      associated with a similar risk of extrapyramidal side-effects as some atypical
      antipsychotics, and this should be clarified in larger, well-designed trials.

PMID- 16625563
TI  - Penfluridol for schizophrenia.
AB  - BACKGROUND: Penfluridol, available since 1970, is an unusual long acting oral
      antipsychotic agent for the treatment of schizophrenia. It may be considered a
      depot medication as it is administered once a week. OBJECTIVES: To review the
      effects of penfluridol for treatment of those with schizophrenia and
      schizophrenia-like illnesses in comparison to placebo, other antipsychotic
      medication or no intervention. SEARCH STRATEGY: We undertook electronic searches
      of the Cochrane Schizophrenia Group's Register (2005), the Cochrane Central
      Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched
      references of all identified studies and sought citations of these studies in the
      Science Citation Index. We contacted the authors of trials and the manufacturer
      of penfluridol. SELECTION CRITERIA: We reliably selected all randomised clinical
      trials comparing penfluridol to placebo or typical or atypical antipsychotic
      drugs for schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS:
      We independently extracted and analysed data on an intention-to-treat basis. We
      calculated the relative risk (RR) and 95% confidence intervals (CI) of
      homogeneous dichotomous data using a random effects model, and where possible
      calculated the number needed to treat. We calculated weighted mean differences
      (WMD) for continuous data. MAIN RESULTS: We included twenty-five studies with a
      total of 1024 participants. Most of these studies were undertaken in the 1970s
      when penfluridol was launched. Ten studies, with 365 patients, compared
      penfluridol to placebo. In the meta-analysis of medium-term lasting studies,
      penfluridol was superior to placebo in the main efficacy measures: 'improvement
      in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and
      'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3
      CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to
      penfluridol or oral typical antipsychotics. There were no particular differences
      between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine,
      thioridazine, or thiothixene for the main outcome measures in medium-term trials:
      'improvement on global state' (N=2 studies), 'leaving the study early' (N=6),
      'needing additional antipsychotic' (N=3), needing antiparkinsonian medication
      (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to
      depot typical antipsychotics. In general, for the efficacy and safety measures,
      no differences were established, but penfluridol was superior in keeping the
      patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to
      0.97, NNT 6 CI 3.4 to 50). AUTHORS' CONCLUSIONS: Although there are shortcomings
      and gaps in the data, there appears to be enough overall consistency for
      different outcomes. The efficacy and adverse effects profile of penfluridol are
      similar to other typical antipsychotics; both oral and depot. Furthermore,
      penfluridol is shown to be an adequate treatment option for people with
      schizophrenia, especially those who do not respond to oral medication on a daily
      basis and do not adapt well to depot drugs. One of the results favouring
      penfluridol was a lower drop out rate in medium term when compared to depot
      medications. It is also an option for chronic sufferers of schizophrenia with
      residual psychotic symptoms who nevertheless need continuous use of antipsychotic
      medication. An additional benefit of penfluridol is that it is a low-cost
      intervention.

PMID- 16625564
TI  - Electromagnetic therapy for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers are defined as areas "of localized damage to the skin
      and underlying tissue caused by pressure, shear, friction and/or the combination
      of these". In the UK, pressure ulcers occur in 5 to 32% of District General
      Hospitals people and in 4 to 7% of people in community settings. Electromagnetic
      therapy, in which electrodes produce an electromagnetic field across the wound,
      may improve healing of chronic wounds such as pressure ulcers. OBJECTIVES: To
      assess the effects of electromagnetic therapy on the healing of pressure ulcers.
      SEARCH STRATEGY: For this first update, we searched the Cochrane Wounds Group
      Specialised Register (last searched October 2005); CENTRAL (The Cochrane Library
      2005, Issue 4); MEDLINE (1966 to October 2005); EMBASE (1980 to October 2005);
      and CINAHL (1982 to October 2005). SELECTION CRITERIA: Randomised controlled
      trials comparing electromagnetic therapy with sham electromagnetic therapy, or
      other (standard) treatment. DATA COLLECTION AND ANALYSIS: For this first update,
      two authors independently scrutinized the results of the search to identify
      relevant RCTs and obtained full reports of potentially eligible studies. For the
      original review, details of eligible studies were extracted and summarised using
      a data extraction sheet. Attempts were made to obtain missing data by contacting
      authors. Data extraction was checked by a second author. Meta-analysis was
      applied to combine the results of trials when the interventions and outcome
      measures were sufficiently similar. MAIN RESULTS: This update identified no new
      trials. Two RCTs were identified for inclusion in the original review (total of
      60 participants). One was a three-armed study comparing electromagnetic therapy
      with electromagnetic therapy in combination with standard therapy, and with
      standard therapy alone, on 17 female and 13 male with grade II and III pressure
      ulcers. The other study compared electromagnetic therapy with sham therapy in 30
      male participants with a spinal cord injury and a grade II or grade III pressure
      ulcer.Neither study found a statistically significant difference between the
      healing rates of pressure ulcers in people treated with electromagnetic therapy
      compared with those in the control group. AUTHORS' CONCLUSIONS: The results
      provide no evidence of benefit in using electromagnetic therapy to treat pressure
      ulcers. However, the possibility of a beneficial or harmful effect cannot be
      ruled out, due to the fact that there were only two included trials both with
      methodological limitations and small numbers of participants. Further research is
      recommended.

PMID- 16625565
TI  - Electromagnetic therapy for treating venous leg ulcers.
AB  - BACKGROUND: Leg ulceration is a common, chronic, recurring condition. The
      estimated prevalence of leg ulcers in the UK population is 1.5 to 3 per 1000.
      Venous ulcers (also called stasis, or varicose ulcers) comprise 80 to 85% of all
      leg ulcers. Electromagnetic therapy is sometimes used as a treatment to assist
      the healing of chronic wounds such as venous leg ulcers. OBJECTIVES: To assess
      the effects of electromagnetic therapy on the healing of venous leg ulcers.
      SEARCH STRATEGY: For this first review update, we searched the Cochrane Wounds
      Group Specialised Register (last searched October 2005); CENTRAL (The Cochrane
      Library 2005, Issue 4); MEDLINE (1966 to October 2005); EMBASE (1980 to October
      2005); and CINAHL (1982 to October 2005). SELECTION CRITERIA: Randomised
      controlled trials comparing electromagnetic therapy with sham electromagnetic
      therapy or other treatments. DATA COLLECTION AND ANALYSIS: For the original
      review, details of eligible studies were extracted and summarised using a data
      extraction sheet. Attempts were made to obtain missing data by contacting
      authors. A second reviewer checked data extraction. Meta-analysis was applied to
      combine the results of trials where the interventions and outcome measures were
      adequately similar. For this first update, two reviewers independently
      scrutinized the results of the search to identify relevant RCTs and obtained full
      reports of potentially eligible studies. In the case of disagreements, a final
      decision was made either after discussion between two reviewers or consultation
      with a third party (a member of the Cochrane Wounds Group). MAIN RESULTS: This
      update identified no new trials. A total of three eligible RCTs were identified
      by the original review. Two trials compared the use of electromagnetic therapy
      with sham therapy and one trial compared it with standard topical treatments. One
      trial found a difference in healing rates of borderline statistical significance
      between electromagnetic therapy and sham therapy, although the direction of
      treatment effect was consistently in favour of electromagnetic therapy, the
      difference was not statistically significant. AUTHORS' CONCLUSIONS: There is
      currently no reliable evidence of benefit of electromagnetic therapy in the
      healing of venous leg ulcers. Further research is needed.

PMID- 16625566
TI  - Inhaled hyperosmolar agents for bronchiectasis.
AB  - BACKGROUND: Mucus retention in the lungs is a prominent feature of
      bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria,
      which elicit a host neutrophilic response. This fails to eliminate the bacteria,
      and the large concentration of host-derived protease may contribute to the airway
      damage. The sensation of retained mucus is itself a cause of suffering, and the
      failure to maintain airway sterility probably contributes to the frequent
      respiratory infections experienced by many patients. Hypertonic saline inhalation
      is known to accelerate tracheobronchial clearance in many conditions, probably by
      inducing a liquid flux into the airway surface, which alters mucus rheology in a
      way favourable to mucociliary clearance. Inhaled dry powder mannitol has a
      similar effect. Such agents are an attractive approach to the problem of
      mucostasis, and deserve further clinical evaluation. OBJECTIVES: To determine
      whether inhaled hyperosmolar substances are efficacious in the treatment of
      bronchiectasis SEARCH STRATEGY: The Cochrane Airways Group Specialised Register
      was searched, and leaders in the field were contacted. Searches were current as
      of October 2005. Search updates will be run annually. SELECTION CRITERIA: Any
      trial using hyperosmolar inhalation in patients with bronchiectasis not caused by
      cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers assessed studies for
      suitability. MAIN RESULTS: Two small studies met the inclusion criteria of the
      review (28 participants). One study reported tracheobronchial clearance of a
      particulate radio aerosol after inhalation of dry mannitol on a single occasion,
      with appropriate control. Airway clearance doubled in the central and
      intermediate regions of the lung, but not in the peripheral region, after
      mannitol administration. No side effects were observed, but two patients were
      premedicated with nedocromil to prevent bronchospasm. Findings from one further
      trial indicated that one domain of a sensitive health status instrument showed a
      favourable response to mannitol. AUTHORS' CONCLUSIONS: Dry powder mannitol has
      been shown to improve tracheobronchial clearance in bronchiectasis, as well as
      cystic fibrosis, asthmatics, and normal subjects. Hypertonic saline has not been
      specifically tested in bronchiectasis, but improves clearance in these other
      conditions and in chronic bronchitis. The measurement of health status in one of
      the studies should be repeated in future longer term randomised controlled
      studies of mannitol and hypertonic saline. Consideration should also be given to
      exacerbations and symptom scores, as well as drug-related adverse events.

PMID- 16625567
TI  - Drug therapy for obstructive sleep apnoea in adults.
AB  - BACKGROUND: The treatment of choice for moderate to severe obstructive sleep
      apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during
      sleep. However this is not tolerated by all patients and its role in mild OSA is
      not proven. Drug therapy has been proposed as an alternative to CPAP in some
      patients with mild to moderate sleep apnoea and could be of value in patients
      intolerant of CPAP. A number of mechanisms have been proposed by which drugs
      could reduce the severity of OSA. These include an increase in tone in the upper
      airway dilator muscles, an increase in ventilatory drive, a reduction in the
      proportion of REM sleep, an increase in cholinergic tone during sleep, a
      reduction in airway resistance and a reduction in surface tension in the upper
      airway. OBJECTIVES: To determine the efficacy of drug therapies in the treatment
      of sleep apnoea. SEARCH STRATEGY: We carried out searches on the Cochrane Airways
      Group Specialised Register of trials. Searches were current as of July 2005.
      SELECTION CRITERIA: Randomised, placebo controlled trials involving adult
      patients with confirmed OSA . We excluded trials if continuous positive airways
      pressure, mandibular devices or oxygen therapy were used. No restriction was
      placed upon publication language or trial duration. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed studies for inclusion, undertook data
      extraction according to pre-specified entry criteria, and quality assessment of
      studies. No response for further information was forthcoming from study authors.
      Results were expressed as mean differences and 95% Confidence Intervals (CI).
      MAIN RESULTS: Twenty-six trials of 21 drugs, involving 394 participants
      contributed data to the review. Most of the studies were small and many trials
      had methodological limitations. Each of the studies states that the subjects had
      OSA but diagnostic criteria were not always explicit and it is possible that some
      patients with central apnoeas may have been recruited. Six drugs had some impact
      on OSA severity and two altered daytime symptoms. One study reported that apnoea
      hypopnea index (AHI) was lower following treatment with intranasal fluticasone
      compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and
      rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave
      an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study
      Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10
      participants). Topical nasal lubricant given twice overnight resulted in an AHI
      of 14 compared to 24 with placebo (10 participants). These three latter studies
      were of single night crossover design and so there are no data on the
      acceptability of these treatments or their effect on symptoms. Paroxetine was
      shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20
      participants tolerated the treatment but there was no improvement in daytime
      symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine
      patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic
      benefit from the drug and it was poorly tolerated in the long term. Protriptyline
      led to a symptomatic improvement (improved versus not improved) in two out of
      three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to
      301.1) but there was no change in the apnoea frequency. In one trial naltrexone
      did reduce AHI, but total sleep time favoured placebo. No significant beneficial
      effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril,
      buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole.
      AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of drug
      therapy in the treatment of OSA. Small studies have reported positive effects of
      certain agents on short-term outcome. Certain agents have been shown to reduce
      the AHI in largely unselected populations with OSA by between 24 and 45%. For
      fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer
      duration are required to establish whether this has an impact on daytime
      symptoms. Individual patients had more complete responses to particular drugs. It
      is likely that better matching of drugs to patients according to the dominant
      mechanism of their OSA will lead to better results and this also needs further
      study.

PMID- 16625568
TI  - Community animal health services for improving household wealth and health status
      of low income farmers.
AB  - BACKGROUND: Community animal health services in low-income countries aim to
      improve the health of animals and directly improve the wealth and health or
      livelihood of their owners. These services have been promoted by aid
      organizations since the 1970s. OBJECTIVES: To summarize reliable research of
      community animal health services on indicators for household wealth and health.
      SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized
      Register (July 2005), CENTRAL (The Cochrane Library 2005, Issue 2), MEDLINE (1966
      to July 2002), AGRIS (1975 to July 2005), Science Citation Index (2000 to July
      2005), STN SIGLE database (1976 to 2002), and AGRICOLA (19 July 2005). We
      contacted relevant researchers and organizations, and also checked the reference
      lists of articles. SELECTION CRITERIA: Randomized controlled trials and
      controlled before-and-after studies comparing community animal health services
      with no community animal health services or with an alternative animal health
      service. DATA COLLECTION AND ANALYSIS: We independently assessed studies for
      inclusion in the review. MAIN RESULTS: No studies met the inclusion criteria.
      AUTHORS' CONCLUSIONS: Well-designed randomized controlled trials or controlled
      before-and-after studies that use standard pragmatic outcomes are needed to
      evaluate the positive results reported by observational studies.

PMID- 16625569
TI  - Hyaluronidase for cervical ripening and induction of labour.
AB  - BACKGROUND: Dilatation and effacement of the cervix are not only a result of
      uterine contractions, but are also dependent upon ripening processes within the
      cervix. The cervix is a fibrous organ composed principally of hyaluronic acid,
      collagen and proteoglycan. Hyaluronic acid increases markedly after the onset of
      labour. An increase in the level of hyaluronic acid is associated with an
      increase in tissue water content. Cervical ripening during labour is
      characterised by changes of the cervix and an increased water content. Cervical
      injection of hyaluronidase was postulated to increase cervical ripening. This is
      one of a series of reviews of methods of cervical ripening and labour induction
      using standardised methodology. OBJECTIVES: To determine the effects of
      hyaluronidase for third trimester cervical ripening or induction of labour in
      comparison with other methods of induction of labour. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (January
      2006) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials
      of hyaluronidase for third trimester cervical ripening or labour induction. DATA
      COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume
      and complexity of trial data relating to labour induction. This involved a two
      stage method of data extraction. We assessed trial quality. We contacted study
      authors for additional information. We collected adverse effects information from
      the trials. MAIN RESULTS: One trial, with 168 women participating, was included
      in the review. When compared with placebo for cervical ripening intracervical
      injections of hyaluronidase resulted in women receiving significantly fewer
      caesarean sections (18% versus 49%, relative risk (RR) 0.37, 95% confidence
      interval (CI) 0.22 to 0.61), less need for oxytocin augmentation (10% versus 47%,
      RR 0.20, 95% CI 0.10 to 0.41), and increased cervical favourability after 24
      hours (60% versus 98%, RR 0.62, 95% CI 0.52 to 0.74). No side-effects for mother
      or baby were reported in this trial. AUTHORS' CONCLUSIONS: Intracervical
      injections of hyaluronidase for cervical ripening appear beneficial. However,
      this is not common practice. In addition it is an invasive procedure that women
      may find unacceptable in the presence of less invasive methods.

PMID- 16625570
TI  - Corticosteroids for cervical ripening and induction of labour.
AB  - BACKGROUND: The role of corticosteroids in the process of labour is not well
      understood. Animal studies have shown the importance of cortisol secretion by the
      fetal adrenal gland in initiating labour in sheep. Infusion of
      glucocorticosteroids into the fetus has also shown to induce premature labour in
      sheep. Given these studies it has been postulated that corticosteroids will
      promote the induction of labour in women. This is one of a series of reviews of
      methods of cervical ripening and labour induction using standardised methodology.
      OBJECTIVES: To determine the effects of corticosteroids for third trimester
      cervical ripening or induction of labour in comparison with other methods of
      cervical priming or induction of labour. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group Trials Register (December 2005) and
      bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials of
      corticosteroids for third trimester cervical ripening or labour induction. DATA
      COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume
      and complexity of trial data relating to labour induction. This involved a two
      stage method of data extraction. We assessed trial quality. We contacted study
      authors for additional information. We collected adverse effects information from
      the trials. MAIN RESULTS: Only one small trial (66 women) was included. The
      primary outcome vaginal birth within 24 hours was not reported. No benefit of
      intramuscular administration of corticosteroids with intravenous oxytocin was
      found when compared with oxytocin alone. However, given the small size of this
      trial this result should be interpreted cautiously. AUTHORS' CONCLUSIONS: The
      effectiveness of corticosteroids for induction of labour is uncertain. This
      method of induction of labour is not commonly used and so further research in
      this area is probably unwarranted.

PMID- 16625571
TI  - Positive expiratory pressure physiotherapy for airway clearance in people with
      cystic fibrosis.
AB  - BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of
      airway secretions in people with cystic fibrosis (CF). Positive expiratory
      pressure (PEP) devices provide constant back pressure to the airways during
      expiration. This may improve clearance by building up gas behind mucus via
      collateral ventilation. Given the widespread use of PEP devices, there is a need
      to determine the evidence for their effect. OBJECTIVES: To determine the
      effectiveness and acceptability of PEP devices compared to other forms of
      physiotherapy as a means of improving mucus clearance and other outcomes in
      people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group Trials Register comprising of references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings. The electronic database CINAHL was
      also searched from 1982 to 2001. Most recent search of the Group's register:
      February 2006. SELECTION CRITERIA: Randomised controlled studies in which PEP was
      compared with any other form of physiotherapy in people with CF. DATA COLLECTION
      AND ANALYSIS: Two authors independently applied the inclusion and exclusion
      criteria to publications and assessed the quality of the included studies. MAIN
      RESULTS: Forty studies were identified and twenty-five studies involving 507
      participants met the review inclusion criteria. Most included studies had low
      scores on a scale of study quality. Twenty of these studies involving 300
      participants were cross-over in design. Data were not published in sufficient
      detail in most of these studies to perform meta-analysis.Forced expiratory volume
      in one second (FEV1) was the most frequently measured outcome. Single
      interventions or series of treatments continued for up to three months
      demonstrated no significant difference in effect between PEP and other methods of
      airway clearance on FEV1. Long-term studies had equivocal or conflicting results
      regarding the effect on FEV1. Participant preference was reported in nine
      studies. In all studies with an intervention period of at least one month,
      measures of participant preference were in favour of PEP. The results for the
      remaining outcome measures were not examined or reported in sufficient detail to
      provide any high level evidence. AUTHORS' CONCLUSIONS: There was no clear
      evidence that PEP was a more or less effective intervention overall than other
      forms of physiotherapy. There was limited evidence that PEP was preferred by
      participants compared to other techniques, but this finding is from studies of
      low quality.

PMID- 16625572
TI  - Memantine for dementia.
AB  - BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may
      prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy
      and safety of memantine for people with Alzheimer's disease (AD), vascular (VD)
      and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group was searched on 8th February 2006. This
      register contains references from all major healthcare databases and many ongoing
      trial databases and is updated regularly. In addition, the search engines
      Copernic and Google were used to identify unpublished trials through inspection
      of the websites of licensing bodies like the FDA , EMEA and NICE and of
      companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials
      registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled,
      randomized trials of memantine in people with dementia. DATA COLLECTION AND
      ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed
      case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out
      of three six month studies show a small beneficial effect of memantine. Pooled
      data indicate a beneficial effect at six months on cognition (2.97 points on the
      100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living
      (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and
      behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004),
      supported by clinical impression of change (0.28 points on the 7 point CIBIC+,
      95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three
      unpublished studies indicate a marginal beneficial effect at six months on ITT
      cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01)
      which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25,
      P = 0.03) but no effect on behaviour, activities of daily living or OC analysis
      of cognition.3. Mild to moderate vascular dementia. Pooled data from two six
      month studies indicated a small beneficial effect of memantine on cognition (1.85
      ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI
      0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4.
      Patients taking memantine were slightly less likely to develop agitation
      (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04).
      This effect was slightly larger, but still small, in moderate to severe AD
      (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There
      is no evidence either way about whether it has an effect on agitation which is
      already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Memantine
      has a small beneficial effect at six months in moderate to severe AD. In patients
      with mild to moderate dementia, the small beneficial effect on cognition was not
      clinically detectable in those with vascular dementia and was detectable in those
      with AD. Memantine is well tolerated.

PMID- 16625573
TI  - Metrifonate for Alzheimer's disease.
AB  - BACKGROUND: Metrifonate is a long-acting irreversible cholinesterase inhibitor,
      originally used to treat schistosomiasis. Its potential to enhance central
      nervous system cholinergic neurotransmission led to clinical trials for the
      treatment of people with Alzheimer's disease (AD). Although low incidence of
      serious side effects occurred during short-term use as an antihelmintic, in
      studies of the treatment of AD extending over 6 months, 20 patients experienced
      respiratory paralysis and problems with neuromuscular transmission. These
      findings have led to a halt to trials of metrifonate for AD and Bayer, the
      pharmaceutical company, has withdrawn its FDA application. OBJECTIVES: 1) To
      establish the efficacy of metrifonate for patients with Alzheimer's disease, in
      terms of cognition, global impression, functional activity, non cognitive
      symptoms, rate of institutionalization and mortality.2) Assess the safety and
      tolerability of metrifonate. SEARCH STRATEGY: The Cochrane Dementia and Cognitive
      Improvement Group's Specialized Register was searched on 5 December 2005 using
      the term metrifonat*. This Register is regularly updated with records from all
      major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials
      databases. One of the authors (LS), as member of the Metrifonate Study Group has
      had the opportunity to contact other metrifonate trialists to obtain data from
      potentially non published data of metrifonate clinical trials. SELECTION
      CRITERIA: All unconfounded, randomized double-blind clinical controlled trials
      comparing metrifonate to placebo in people with AD. DATA COLLECTION AND ANALYSIS:
      Data were extracted by the two reviewers, cross-checked, and pooled when
      appropriate and possible. MAIN RESULTS: Most studies assessed changes in
      cognitive function, global function, activities of daily living, behavioural
      problems, severity of disease and adverse events. Occasionally the results were
      not reported in sufficient detail to allow extraction of data for the meta
      analyses. The treatment regimens were varied: loading doses were used in some
      trials. The range of maintenance doses and studies were not pooled unless the
      treatment regimens were considered comparable. The lengths of treatment varied
      from 6 to 26 weeks and studies were not pooled unless the treatment duration was
      similar. The results are derived from the ITT populations. Metrifonate at various
      doses, fixed and loading doses, was associated with significant cognitive
      improvement compared to placebo, except for weekly doses where there was no
      difference from placebo: MMSE (metrifonate 60-80 mg/day with initial loading at
      26 weeks; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD
      1.85, 95% CI 1.06 to 2.64, p<0.00001); ADAS-Cog (metrifonate 60-80 mg/day with
      initial loading at 26 weeks MD -3.24, 95% CI -4.40 to -2.08, p<0.00001)In most
      trials, there was improvement in clinical global impression: CIBIC-Plus
      (metrifonate 30-55 mg/day, approximately 0.65 mg/kg body weight, with initial
      loading at 26 weeks MD -0.25, 95% CI -0.41 to -0.09 p=0.002; metrifonate 50
      mg/day fixed dose with no initial loading at 26 weeks MD -0.20, 95% CI -0.39 to 
      0.01, p=0.04). There were generally-significant drug-placebo differences in
      activities of daily living but this often depended on sample size and the
      characteristics of the instrument used: DAD (metrifonate 30-55 mg/day, 0.65 mg/kg
      body weight, with initial loading at 26 weeks MD 2.72, 95% CI 0.66 to 4.77,
      p=0.01; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD
      4.07, 95% CI 0.29 to 7.85, p=0.03)Also there were differences associated with
      metrifonate compared with placebo for different doses of metrifonate in scores on
      a behavioural symptom scale, caregiver burden scale, and severity of disease
      scale. Adverse events occurring more often with metrifonate included abdominal
      pain, bloating, bradycardia, diarrhoea, leg cramps, nausea and rhinitis and were
      described as mostly mild and transient, but occasionally moderately severe, and
      infrequently severe and serious. Analysis of the number of patients suffering at
      least one mild, moderate, severe or serious adverse event before the end of
      treatment showed that there was usually no difference between placebo and
      metrifonate. AUTHORS' CONCLUSIONS: Metrifonate given once per day appears to be
      related to clinical response in cognition, global improvement, and activities of
      daily living in patients with mild to moderate Alzheimer's disease. Tolerability
      is good with adverse events as expected from a cholinesterase inhibitor, but with
      a low incidence of neuromuscular dysfunction and respiratory failure, too low to
      be detected in this review. It has been withdrawn from further development.

PMID- 16625574
TI  - Electrostimulation for promoting recovery of movement or functional ability after
      stroke.
AB  - BACKGROUND: Electrostimulation might improve motor recovery after stroke by
      providing neuromuscular re-training. OBJECTIVES: To find if electrostimulation
      improved functional motor ability, and the ability to undertake activities of
      daily living. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched August 2005), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to January
      2004), EMBASE (1980 to January 2004), CINAHL (1982 to January 2004), AMED -
      Allied and Complementary Medicine Database (1985 to January 2004), Physiotherapy
      Evidence Database (PEDro), REHABDATA and the ISI Science Citation Index (1981 to
      2003). We placed a request on the PHYSIO e-mail discussion list and contacted
      authors of relevant studies to elicit any unpublished or ongoing studies,
      searched the reference lists of included trials and contacted trialists.
      SELECTION CRITERIA: Randomised controlled trials of electrostimulation delivered
      to the peripheral neuromuscular system which was designed to improve voluntary
      movement control, functional motor ability and activities of daily living. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials for
      inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Of the
      2077 references identified, 24 trials were included in this review. For
      electrostimulation compared with no treatment this review found that
      electrostimulation improved some aspects of functional motor ability and some
      aspects of motor impairment and normality of movement. In addition, there was a
      significant difference in favour of no treatment compared with electrostimulation
      for an aspect of functional motor ability. For electrostimulation compared with
      placebo this review found that electrostimulation improved an aspect of
      functional motor ability. For electrostimulation compared with conventional
      physical therapy this review found that electrostimulation improved an aspect of
      motor impairment. There were no statistically significant differences between
      electrostimulation and control treatment for all other outcomes. However, these
      results need to be interpreted with reference to the following: (1) the majority
      of analyses only contained one trial; (2) variation was found between included
      trials in time after stroke, level of functional deficit, and dose of
      electrostimulation; and (3) the possibility of selection and detection bias in
      the majority of included trials. AUTHORS' CONCLUSIONS: At present, there are
      insufficient robust data to inform clinical use of electrostimulation for
      neuromuscular re-training. Research is needed to address specific questions about
      the type of electrostimulation that might be most effective, in what dose and at
      what time after stroke.

PMID- 16625575
TI  - Short acting insulin analogues versus regular human insulin in patients with
      diabetes mellitus.
AB  - BACKGROUND: Short acting insulin analogue use for diabetic patients is still
      controversial, as reflected in many scientific debates. OBJECTIVES: To assess the
      effects of short acting insulin analogues versus regular human insulin. SEARCH
      STRATEGY: The Cochrane Library (Issue 3, 2005), MEDLINE, EMBASE until September
      2005. SELECTION CRITERIA: Randomised controlled trials with an intervention
      duration of at least 4 weeks. DATA COLLECTION AND ANALYSIS: Trial selection and
      evaluation of study quality was done independently by two reviewers. MAIN
      RESULTS: Altogether 8274 participants took part in 49 randomised controlled
      studies. Most studies were of poor methodological quality. In patients with type
      1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2
      to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes
      the WMD was 0.0% (95% CI: -0.1 to 0.0). In subgroup analyses of different types
      of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI:
      -0.3 to -0.1) in favour of insulin analogue in studies using continuous
      subcutaneous insulin injections (CSII), whereas for conventional intensified
      insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0).
      The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2
      (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison
      to regular insulin in patients with type 1 diabetes and type 2 diabetes,
      respectively. For studies in type 1 diabetes patients the incidence of severe
      hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years
      for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in
      type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person
      years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin.
      No study was designed to investigate possible long term effects (e.g. mortality,
      diabetic complications), in particular in patients with diabetes related
      complications. AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit
      of short acting insulin analogues in the majority of diabetic patients treated
      with insulin. Until long term efficacy and safety data are available we suggest a
      cautious response to the vigorous promotion of insulin analogues. For safety
      purposes, we need a long-term follow-up of large numbers of patients and well
      designed studies in pregnant women to determine the safety profile for both the
      mother and the unborn child.

PMID- 16625576
TI  - Strategies for integrating primary health services in middle- and low-income
      countries at the point of delivery.
AB  - BACKGROUND: Strategies to integrate primary health care aim to bring together
      inputs, organisation, management and delivery of particular service functions to
      make them more efficient, and accessible to the service user. In some middle and
      low income countries, services have been fragmented by separate vertical
      programmes established to ensure delivery of particular technologies. We examined
      the effectiveness of integration strategies at the point of delivery. OBJECTIVES:
      To assess the effects of strategies to integrate primary health care services on
      producing a more coherent product and improving health care delivery and health
      status. SEARCH STRATEGY: We searched the Cochrane Effective Practice and
      Organisation of Care Group specialised register (August 2005), MEDLINE (1966 to
      September 2005), EMBASE (1988 to 2005), Socio Files (1974 to September 2005),
      Popline (1970 to September 2005), HealthStar (1975 to September 2005), Cinahl
      (1982 to September 2005); Cab Health (1972 to 1999), International Bibliography
      of the Social Sciences (1970 to 1999), and reference lists of articles. We also
      searched the Internet and World Health Organization (WHO) library database, hand
      searched relevant WHO publications and contacted experts in the field. SELECTION
      CRITERIA: Randomised trials, controlled before and after studies, and interrupted
      time series analyses of integration strategies in primary health care services.
      Health services in high-income countries were excluded. The primary outcomes were
      indicators of health care delivery, user views on any measure of service
      coherence, and health status. We also sought information on comparative costs.
      DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and
      assessed study quality. MAIN RESULTS: Three cluster randomised trials and two
      controlled before and after studies were included, with three types of
      comparison: integration by adding on an additional component to an existing
      service (family planning); integrated services versus single special services
      (for sex workers); integrated delivery systems versus a vertical service (for
      family planning); and packages of enhanced primary child care services
      (integrated management of childhood illnesses) vs. routine child care.
      Interventions were complex and in some studies inputs varied substantially
      between comparison arms. Overall, no consistent pattern emerged. Only one study
      attempted to assess the user's view of the service provided. AUTHORS'
      CONCLUSIONS: Few studies of good quality, large and with rigorous study design
      have been carried out to investigate strategies to promote service integration in
      low and middle income countries. All describe the service supply side, and none
      examine or measure aspects of the demand side. Future studies must also assess
      the client's view, as this will influence uptake of integration strategies and
      their effectiveness on community health.

PMID- 16625577
TI  - Surgical versus endoscopic treatment of bile duct stones.
AB  - BACKGROUND: 10% to 18% of patients undergoing cholecystectomy for gallstones have
      common bile duct (CBD) stones. Treatment options for these stones include pre- or
      post-operative endoscopic retrograde cholangiopancreatography (ERCP) or open or
      laparoscopic surgery. OBJECTIVES: To systematically review the management of CBD
      stones by four approaches: (1) ERCP versus open surgical bile duct clearance. (2)
      Pre-operative ERCP versus laparoscopic bile duct clearance. (3) Post-operative
      ERCP versus laparoscopic bile duct clearance. (4) ERCP versus laparoscopic bile
      duct clearance in patients with previous cholecystectomy. SEARCH STRATEGY: We
      systematically searched key relevant electronic databases, bibliographies of
      relevant papers, and abstracts of relevant subspecialty meetings until November
      2005. SELECTION CRITERIA: The quality of included trials was assessed by adequacy
      of allocation sequence generation, allocation concealment, blinding, and follow
      up. DATA COLLECTION AND ANALYSIS: Published and unpublished data relevant to 12
      predefined outcome measures were used to conduct fixed- and random-effects models
      meta-analyses, with exploration of heterogeneity and use of sensitivity and
      subgroup analysis where required. MAIN RESULTS: Thirteen trials randomised 1351
      patients. Eight trials (n = 760) compared ERCP with open surgical clearance,
      three (n = 425) compared pre-operative ERCP with laparoscopic clearance, and two
      (n = 166) compared post-operative ERCP with laparoscopic clearance. There were no
      trials of ERCP versus laparoscopic clearance in patients without an intact
      gallbladder. Methodology was considered adequate in at least two of three
      assessable fields in ten trials. A significantly increased number of total
      procedures (including for complications) per patient was seen in the ERCP arms in
      all three comparisons with weighted mean differences of 0.62 (95% CI 0.15 to
      1.09), 0.96 (95% CI 0.96 to 0.96), and 1.09 (95% CI 0.93 to 1.24), respectively.
      ERCP was less successful than open surgery in CBD stone clearance (Peto OR 2.89,
      95% CI 1.81 to 4.61) with a tendency towards higher mortality (risk difference
      1%, 95% CI -1% to 4%). Laparoscopic CBD stone clearance was as efficient as pre-
      (Peto OR 1.00, CI 0.53 to 1.80) and post-operative ERCP (OR 2.27, 95% CI 0.37 to
      13.9) and with no significant difference in morbidity and mortality. Laparoscopic
      trials universally reported shorter hospital stays in surgical arms. Insufficient
      data were reported for cost analysis. AUTHORS' CONCLUSIONS: In the era of open
      cholecystectomy, open bile duct surgery was superior to ERCP in achieving CBD
      stone clearance. In the laparoscopic era, data are close to excluding a
      significant difference between laparoscopic and ERCP clearance of CBD stones. The
      use of ERCP necessitates increased number of procedures per patient.

PMID- 16625578
TI  - Interventions for paracetamol (acetaminophen) overdose.
AB  - BACKGROUND: Poisoning with paracetamol (acetaminophen) is a common cause of
      hepatotoxicity in the Western World. Inhibition of absorption, removal from the
      vascular system, antidotes, and liver transplantation are interventions for
      paracetamol poisoning. OBJECTIVES: To assess the benefits and harms of
      interventions for paracetamol overdose. SEARCH STRATEGY: We identified trials
      through electronic databases, manual searches of bibliographies and journals,
      authors of trials, and pharmaceutical companies until December 2005. SELECTION
      CRITERIA: Randomised clinical trials and observational studies were included.
      DATA COLLECTION AND ANALYSIS: The primary outcome measure was all-cause mortality
      plus liver transplantation. Secondary outcome measures were clinical symptoms,
      (eg, hepatic encephalopathy, fulminant hepatic failure), hepatotoxicity, adverse
      events, and plasma paracetamol concentration. We used Peto odds ratios and odds
      ratios with 95% confidence intervals (CI) for analysis of outcomes. Random- and
      fixed-effects meta-analyses were performed. MAIN RESULTS: Ten small and low
      methodological quality randomised trials, one quasi-randomised study, and 48
      observational studies were identified. It was not possible to perform relevant
      meta-analyses of randomised trials that have addressed our outcome measures.
      Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the
      absorption of paracetamol, but the clinical benefit is unclear. Of these,
      activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine
      seems preferable to placebo/supportive treatment, dimercaprol, and cysteamine,
      but N-acetylcysteine's superiority to methionine is unproven. It is not clear
      which N-acetylcysteine treatment protocol offers the best efficacy. No strong
      evidence supports other interventions for paracetamol overdose. N-acetylcysteine
      may reduce mortality in patients with fulminant hepatic failure (Peto OR 0.26,
      95% CI 0.09 to 0.94, one trial). Liver transplantation has the potential to be
      life saving in fulminant hepatic failure, but refinement of selection criteria
      for transplantation and long-term outcome reporting are required. AUTHORS'
      CONCLUSIONS: Our results highlight a paucity of randomised trials on
      interventions for paracetamol overdose. Activated charcoal seems the best choice
      to reduce absorption. N-acetylcysteine should be given to patients with overdose
      but the selection criteria are not clear. No N-acetylcysteine regime has been
      shown to be more effective than any other. It is a delicate balance when to
      proceed to liver transplantation, which may be life-saving for patients with poor
      prognosis.

PMID- 16625579
TI  - Directly observed therapy for treating tuberculosis.
AB  - BACKGROUND: People with tuberculosis require treatment for at least six months.
      As many patients do not complete their treatment, policies have been introduced
      to encourage adherence to treatment regimens. One such policy is directly
      observed therapy, which involves people directly observing patients taking their
      antituberculous drugs. OBJECTIVES: To compare directly observed therapy (DOT)
      with self administration of treatment in people requiring treatment for
      clinically active tuberculosis or prevention of active disease. SEARCH STRATEGY:
      We searched the Cochrane Infectious Diseases Group Specialized Register (November
      2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November
      2005), EMBASE (1974 to November 2005), LILACS (1982 to November 2005), and
      reference lists of articles. We also contacted researchers and organizations
      working in the field. SELECTION CRITERIA: Randomized and quasi-randomized
      controlled trials comparing a health worker, family member, or community
      volunteer routinely observing people taking antituberculous drugs compared with
      routine self administration of treatment at home. We include patients requiring
      treatment for clinically active tuberculosis or medication for preventing active
      disease. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial
      methodological quality and extracted data. Data were analysed using relative
      risks (RR) with 95% confidence intervals (CI) and the fixed-effect model when
      there was no statistically significant heterogeneity (chi square P > 0.1). Trials
      of drug users were analysed separately. MAIN RESULTS: Ten trials with 3985
      participants met the inclusion criteria. There was no statistically significant
      difference between DOT and self administration of treatment for the number of
      people cured (RR 1.02, 95% CI 0.86 to 1.21, random-effects model; 1603
      participants, 4 trials) or who were cured or completed treatment (RR 1.06, 95% CI
      1.00 to 1.13; 1603 participants, 4 trials). Stratifying the location of the DOT
      by home or at a clinic suggests a possible small effect with home-based DOT (RR
      1.10, 95% CI 1.02 to 1.18; 1365 participants, 3 trials). Two small trials of
      tuberculosis prophylaxis in intravenous drugs users found no statistically
      significant difference between DOT and self administration (199 participants, 1
      trial), or a choice of location for DOT for completion of treatment (108
      participants, 1 trial). AUTHORS' CONCLUSIONS: The results of randomized
      controlled trials conducted in low-, middle-, and high-income countries provide
      no assurance that directly observed therapy compared with self-administered
      treatment has any quantitatively important effect on cure or treatment completion
      in people receiving treatment for tuberculosis.

PMID- 16625580
TI  - Pain management for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease is an inherited genetic disorder characterized by
      an abnormality of haemoglobin that predisposes to polymerization and consequent
      deformation ("sickling"). Sickle cell disease can cause episodes of acute severe
      pain. Chronic pain may also occur. Currently, pain is inadequately managed.
      OBJECTIVES: The primary aim of the review was to assess the effectiveness of
      pharmacological analgesic interventions for pain management in sickle cell
      disease, including the treatment of acute and chronic pain in children and
      adults. SEARCH STRATEGY: A pre-defined search strategy was used to electronically
      search the MEDLINE and EMBASE databases. Searches were also conducted on the
      Cochrane Controlled Trial Register (CCTR) and the Oxford pain randomised
      controlled trials citation database. The search period covered from January 1965
      through to June 2002. Bibliographies of retrieved studies were searched for
      additional references. No language restriction was used. SELECTION CRITERIA: All
      randomised controlled trials involving pharmacological treatment of acute or
      chronic pain in children or adults with sickle cell disease were selected.
      Patients with haemoglobin SS, haemoglobin S ss thalassaemia and the haemoglobin
      SC group were included. DATA COLLECTION AND ANALYSIS: Trials were quality rated
      using the Oxford quality scale. Continuous measures of outcome were combined
      using weighted mean differences. Overall effect size was calculated with 95%
      confidence intervals. MAIN RESULTS: Nine randomised controlled trials were
      identified. All studies involved small numbers of patients with acute sickle cell
      pain only. Interventions included NSAIDs (versus placebo in four studies; versus
      strong opioids in one study), strong opioids (oral versus parenteral in one
      study; morphine versus alternate in one study) and corticosteroids (versus
      placebo in two studies). Lack of data, small patient numbers, variations in study
      design and outcome measures limited the review. Due to heterogeneity of
      methodologies and reporting, it was not possible to perform meaningful meta
      analyses. AUTHORS' CONCLUSIONS: There were no studies addressing chronic pain in
      sickle cell disease. There is limited evidence for analgesic interventions in
      acute pain crises. Studies have been under-powered. There is not enough data for
      inter-trial comparisons. In one trial, there was no difference in the efficacy of
      sustained-release oral versus parenteral morphine, which suggests that oral
      morphine should be considered for acute pain. Parenteral corticosteroids appear
      to shorten the period over which analgesics are required and hospital length-of
      stay, without producing short-term major adverse effects. More research is needed
      to improve pain management in sickle cell disease.

PMID- 16625581
TI  - Clotting factor concentrates given to prevent bleeding and bleeding-related
      complications in people with hemophilia A or B.
AB  - BACKGROUND: People with severe hemophilia A or B, X-linked bleeding disorders due
      to decreased blood levels of coagulants, suffer recurrent bleeding into joints
      and soft tissues. Before clotting factor concentrates were available, most people
      with severe hemophilia developed crippling musculoskeletal deformities. Clotting
      factor concentrate prophylaxis aims to preserve joint function by converting
      severe hemophilia (factor VIII or IX less than 1%) into a clinically milder form
      of the disease. Prophylaxis has long been used in Sweden, but not universally
      adopted because of medical, psychosocial, and cost controversies. Use of clotting
      factor concentrates is the single largest predictor of cost in treating
      hemophilia. OBJECTIVES: To determine the effectiveness of clotting factor
      concentrate prophylaxis in the management of people with hemophilia A or B.
      SEARCH STRATEGY: We searched the Cystic Fibrosis and Genetic Disorders Group's
      Trials Register comprising references from comprehensive electronic database
      searches and handsearches of journals and abstract books. Reference lists of
      relevant articles were reviewed. Most recent search: November 2005. SELECTION
      CRITERIA: Randomized controlled trials (RCTs) evaluating people with severe
      hemophilia A or B, receiving prophylactic clotting factor concentrates. DATA
      COLLECTION AND ANALYSIS: Two authors independently reviewed studies for
      eligibility, assessed methodological quality and extracted data. MAIN RESULTS:
      Twenty-nine studies were identified; four studies (including 37 participants)
      were eligible for inclusion. Three studies evaluated hemophilia A; one showed a
      decrease in frequency of joint bleeds with prophylaxis compared to placebo (non
      physiological dose), with a rate difference (RD) -10.80 (95% confidence interval
      (CI) -16.33 to -5.27) bleeds per year. The remaining two studies evaluating
      hemophilia A compared two prophylaxis regimens, one study showed no difference in
      joint bleed frequency, RD -5.04 (95%CI -17.02 to 6.94) bleeds per year and
      another failed to demonstrate an advantage of factor VIII dosing based on
      individual pharmacokinetic data over the standard prophylaxis regimen with RD 
      0.14 (95% CI -1.34 to 1.05) bleeds per year. The fourth study evaluated
      hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi
      weekly (7.5 IU/kg) prophylaxis, RD -3.30 (95% CI -5.50 to - 1.10) bleeds per
      year. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised
      controlled trials to determine whether prophylactic clotting factor concentrates
      decrease bleeding and bleeding-related complications in hemophilia A or B,
      compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic
      data from individuals. Well-designed RCTs are needed to assess the effectiveness
      of prophylactic clotting factor concentrates. Two clinical trials are ongoing.

PMID- 16625582
TI  - Low level laser therapy for treating tuberculosis.
AB  - BACKGROUND: The main treatment for tuberculosis is antituberculous drugs. Low
      level laser therapy is used as an adjunct to antituberculous drugs, predominantly
      in the former Soviet Union and India. OBJECTIVES: To compare low level laser
      therapy plus antituberculous drugs with antituberculous drugs alone for treating
      tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group
      Specialized Register (December 2005), CENTRAL (The Cochrane Library 2005, Issue
      4), MEDLINE (1966 to December 2005), EMBASE (1974 to December 2005), CINAHL (1982
      to December 2005), Science Citation Index (1945 to December 2005), PEDro (1929 to
      December 2005), the Central Medical Library of Moscow catalogue (1988 to June
      2005), the internet, and reference lists of articles. We contacted relevant
      organizations and researchers for the original version. SELECTION CRITERIA:
      Randomized trials comparing low level laser therapy plus antituberculous drugs
      with antituberculous drugs alone in people with tuberculosis. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data,
      including adverse events. MAIN RESULTS: One randomized controlled trial (130
      participants) conducted in India met the inclusion criteria. This trial was
      poorly reported, with no information on the generation of allocation sequence or
      allocation concealment. The trial report did not provide details on the group
      that each of the participants were randomized into or which group those
      participants that left the trial were from. This precluded the use of its data on
      time to sputum conversion and other outcome measures for analysis. AUTHORS'
      CONCLUSIONS: The use of low level laser therapy for treating tuberculosis is
      still not supported by reliable evidence. Researchers need to focus on conducting
      well-designed randomized controlled trials to justify the continued participation
      of volunteers for studies of this experimental intervention.

PMID- 16625583
TI  - Expectant care versus surgical treatment for miscarriage.
AB  - BACKGROUND: Miscarriage is a common complication of early pregnancy that can have
      both medical and psychological consequences like depression and anxiety. The need
      for routine surgical evacuation with miscarriage has been questioned because of
      potential complications such as cervical trauma, uterine perforation, hemorrhage,
      or infection. OBJECTIVES: To compare the safety and effectiveness of expectant
      management versus surgical treatment for early pregnancy loss. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December
      2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library
      2004, Issue 3), PubMed (1966 to March 2005), POPLINE (inception to March 2005),
      and LILACS (1982 to March 2005) and reference lists of reviews. SELECTION
      CRITERIA: Randomized trials comparing expectant care and surgical treatment
      (vacuum aspiration or dilation and curettage (D & C)) for miscarriage were
      eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. We contacted study authors for
      additional information. MAIN RESULTS: Five trials were included in this review
      with 689 total participants. The expectant-care group was more likely to have an
      incomplete miscarriage (RR 5.37; 95% CI 2.57 to 11.22). However, the time frames
      for declaring the process incomplete varied across the studies. The need for
      unplanned surgical treatment (such as vacuum aspiration or D&C) was greater for
      the expectant-care group (RR 4.78; 95% CI 1.99 to 11.48). The expectant-care
      group had more days of bleeding (WMD 1.59; 95% CI 0.74 to 2.45) and a greater
      amount of bleeding (WMD 1.00; 95% CI 0.60 to 1.40). Post-procedure diagnosis of
      infection was lower in the expectant-care group (RR 0.29; 95% CI 0.09 to 0.87).
      Information on psychological outcomes and pregnancy was too limited to draw
      conclusions. AUTHORS' CONCLUSIONS: Expectant management led to a higher risk of
      incomplete miscarriage, need for surgical emptying of the uterus, and bleeding.
      None of these were serious. In contrast, surgical evacuation was associated with
      a significantly higher risk of infection. Given the lack of clear superiority of
      either approach, the woman's preference should play a dominant role in decision
      making. Medical management has added choices for women and their clinicians, but
      these were not reviewed here.

PMID- 16625584
TI  - Inhaled corticosteroids versus sodium cromoglycate in children and adults with
      asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) and sodium cromoglycate (SCG) have
      become established as effective controller medications for children and adults
      with asthma, but their relative efficacy is not clear. OBJECTIVES: To compare the
      relative effectiveness and adverse effects of ICS and SCG among children and
      adults with chronic asthma. SEARCH STRATEGY: Systematic search of the Cochrane
      Airways Group's special register of controlled trials (to Feb. 2004), hand
      searches of the reference lists of included trials and relevant review papers,
      and written requests for identification of additional trials from pharmaceutical
      manufacturers. SELECTION CRITERIA: Randomized controlled trials comparing the
      effect of ICS with SCG in children and adults with chronic asthma. DATA
      COLLECTION AND ANALYSIS: All studies were assessed independently for eligibility
      by three review authors. Disagreements were settled by consensus. Trial authors
      were contacted to supply missing data or to verify methods. Eligible studies were
      abstracted and fixed- and random-effects models were implemented to pool studies.
      Separate analyses were conducted for paediatric and adult studies. Subgroup
      analyses and meta-regression models were fit to explore heterogeneity of lung
      function outcomes by type of RCT, category of ICS or SCG dosage, asthma severity
      of participants, and study quality on outcomes. MAIN RESULTS: Of 67 identified
      studies, 17 trials involving 1279 children and eight trials involving 321 adults
      with asthma were eligible. Thirteen (76%) of the paediatric studies and six (75%)
      of the adult studies were judged to be high quality. Among children, ICS were
      associated with a higher final mean forced expiratory volume in 1 second [FEV1]
      (weighted mean difference [WMD] 0.07 litres, 95% confidence interval [CI] 0.02 to
      0.11) and higher mean final peak expiratory flow rate [PEF] (WMD 17.3
      litres/minute, 95% CI 11.3 to 23.3) than SCG. In addition, ICS were associated
      with fewer exacerbations (WMD -1.18 exacerbations per year, 95% CI -2.15 to -
      0.21), lower asthma symptom scores, and less rescue bronchodilator use than SCG.
      There were no group differences in the proportion of children with adverse
      effects. Among adults, ICS were similarly associated with a higher mean final
      FEV1 (WMD 0.21 litres, 95% CI 0.13 to 0.28) and a higher final endpoint PEF (WMD
      28.2 litres/minute, 95% CI 18.7 to 37.6) than SCG. ICS were also associated with
      fewer exacerbations (WMD -3.30 exacerbations per year, 95% CI -5.62 to -0.98),
      lower asthma symptom scores among cross-over trials but not parallel trials, and
      less rescue bronchodilator use than SCG. There were no differences in the
      proportion of adults with adverse effects. In subgroup analyses involving lung
      function measures, paediatric and adult studies judged to be of high quality had
      results consistent with the overall results. Lung function measures in children
      were higher in studies with medium BDP-equivalent steroid dosages than low BDP
      equivalent dosages, while adult studies could not be compared by steroid dosage
      since they all incorporated similar dosages. There were no significant
      differences in lung function by the asthma severity of participants for adult or
      child studies. AUTHORS' CONCLUSIONS: ICS were superior to SCG on measures of lung
      function and asthma control for both adults and children with chronic asthma.
      There were few studies reporting on quality of life and health care utilization,
      which limited our ability to adequately evaluate the relative effects of these
      medications on a broader range of outcomes. Although there were no differences in
      adverse effects between ICS and SCG, most trials were short and may not have been
      of sufficient duration to identify long-term effects. Our results support recent
      consensus statements in the U.S. and elsewhere that favour the use of ICS over
      SCG for control of persistent asthma.

PMID- 16625585
TI  - Anti-IgE for chronic asthma in adults and children.
AB  - BACKGROUND: Omalizumab is a recombinant humanised monoclonal antibody directed
      against immunoglobulin E (anti-IgE) to inhibit the immune system's response to
      allergen exposure. Omalizumab is directed against the binding site of IgE for its
      high affinity Fc receptor. It prevents free serum IgE from attaching to mast
      cells and other effector cells and prevents IgE mediated inflammatory changes.
      OBJECTIVES: To determine the efficacy of anti-IgE compared with placebo in
      patients with allergic asthma SEARCH STRATEGY: We searched the Cochrane Airways
      Group Asthma trials register for potentially relevant studies (February 2006).
      SELECTION CRITERIA: Randomised controlled trials examining anti-IgE administered
      in any manner for any duration. Trials with co-interventions were included as
      long as they were the same in each arm. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed study quality and extracted and entered data.
      Three modes of administration were identified from the published literature
      (inhaled, intravenous and subcutaneous injection). Subgroup analysis was
      performed by asthma severity. Data were extracted from published and unpublished
      sources. MAIN RESULTS: Fourteen trials (15 group comparisons) were included in
      the review, contributing a total of 3143 mild to severe allergic asthmatic
      participants with high levels of IgE. Treatment with intravenous and subcutaneous
      Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led
      to a significant reduction in inhaled steroid (ICS) consumption compared with
      placebo (-119 mcg/day (95% CI -154 to -83, three trials)). There were significant
      increases in the number of participants who were able to reduce ICS by over 50%
      (odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials));
      or completely withdraw their daily ICS intake (OR 2.50 (95%CI 2.00 to 3.13; four
      trials)). Participants treated with Omalizumab were less likely to suffer an
      asthma exacerbation with treatment as an adjunct to ICS (OR 0.52, 95%CI 0.41 to
      0.65, five trials), or as an ICS tapering agent (OR 0.47, 95% CI 0.37 to 0.60,
      four trials). AUTHORS' CONCLUSIONS: Omalizumab was significantly more effective
      than placebo at increasing the numbers of patients who were able to reduce or
      withdraw their inhaled steroids, but the clinical value of the reduction in
      steroid consumption has be considered in the light of the high cost of
      Omalizumab. The impressive placebo effects observed in control groups bring into
      question the true effect of Omalizumab. Omalizumab was effective in reducing
      asthma exacerbations as an adjunctive therapy to inhaled steroids, and during
      steroid tapering phases of clinical trials. Omalizumab was generally well
      tolerated, although there were more injection site reactions with Omalizumab.
      Patient and physician assessments of the drug were positive. Further assessment
      in paediatric populations is necessary, as is direct double-dummy comparison with
      ICS.

PMID- 16625586
TI  - Interventions for idiopathic steroid-resistant nephrotic syndrome in children.
AB  - BACKGROUND: The majority of children who present with their first episode of
      nephrotic syndrome, achieve remission with corticosteroid therapy. Children who
      fail to respond may be treated with immunosuppressive agents such as
      cyclophosphamide, chlorambucil or cyclosporin, or with non-immunosuppressive
      agents such as ACE inhibitors. Optimal combinations of these agents with the
      least toxicity remain to be determined. OBJECTIVES: To evaluate the benefits and
      harms of interventions used to treat idiopathic steroid resistant nephrotic
      syndrome (SRNS) in children. SEARCH STRATEGY: Randomised controlled trials (RCTs)
      were identified from the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, reference lists of articles and abstracts from
      conference proceedings. Date of most recent search: June 2005 SELECTION CRITERIA:
      RCTs and quasi-RCTs were included if they compared different immunosuppressive
      agents or non-immunosuppressive agents with placebo, prednisone or other agent
      given orally or parenterally in children aged three months to 18 years with SRNS.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently searched the
      literature, determined trial eligibility, assessed quality, extracted data and
      entered it in RevMan. For dichotomous outcomes, results were expressed as
      relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the
      random effects model. MAIN RESULTS: Eleven RCTs (312 children) were included.
      Cyclosporin when compared with placebo or no treatment significantly increased
      the number of children who achieved complete remission (three trials, 49
      children: RR for persistent nephrotic syndrome 0.64, 95% CI, 0.47 to 0.88). There
      was no significant difference in the number of children who achieved complete
      remission between oral cyclophosphamide with prednisone and prednisone alone (two
      trials, 91 children: RR 1.01, 95% CI 0.74 to 1.36), between intravenous
      cyclophosphamide and oral cyclophosphamide (one study, 11 children: RR 0.09, 95%
      CI 0.01 to 1.39) and between azathioprine with prednisone and prednisone alone
      (one trial 31 children: RR 1.01, 95% CI 0.77 to 1.32). ACE inhibitors
      significantly reduced proteinuria (two trials, 70 children). After 12 weeks of
      treatment fosinopril reduced proteinuria by 0.95 g/24 h (95% CI -1.21 to -0.69).
      No RCTs were identified comparing combination regimens comprising high dose
      steroids, alkylating agents or cyclosporin with single agents, placebo or no
      treatment. AUTHORS' CONCLUSIONS: Further adequately powered and well designed
      RCTs are needed to confirm the efficacy of cyclosporin and to evaluate other
      regimens for idiopathic SRNS including high dose steroids with alkylating agents
      or cyclosporin.

PMID- 16625587
TI  - Oxcarbazepine versus phenytoin monotherapy for epilepsy.
AB  - BACKGROUND: Worldwide, phenytoin is a commonly used antiepileptic drug.
      Oxcarbazepine is one of the newer antiepileptic drugs and has similar chemical
      properties to its parent compound carbamazepine. For the new drugs such as
      oxcarbazepine, it is important to know how they compare with standard treatments.
      OBJECTIVES: To review the best evidence comparing oxcarbazepine and phenytoin
      when used as monotherapy in patients with epilepsy. SEARCH STRATEGY: We searched
      the Cochrane Epilepsy Group's Specialized Register (December 2005), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3,
      2005), and MEDLINE (1966 to November 2005). No language restrictions were
      imposed. We checked the reference lists of retrieved studies for additional
      reports of relevant studies. We also contacted pharmaceutical companies to try
      and identify any unpublished studies. SELECTION CRITERIA: Randomized controlled
      trials in children or adults with epilepsy. Trials must have included a
      comparison of oxcarbazepine monotherapy with phenytoin monotherapy. DATA
      COLLECTION AND ANALYSIS: This was an individual patient data review. Two review
      authors independently assessed trial quality and extracted data. Study authors
      were contacted for additional information. Outcomes were (a) time on allocated
      treatment; (b) time to achieve 6, 12 and 24-month remission; (c) time to first
      seizure post randomization; (d) quality of life measures if available. Clinical
      heterogeneity was assessed by reviewing differences across trials in
      characteristics of randomized patients, dosing protocols and trial design. Data
      were analysed on an intention to treat basis. Stratified logrank tests were used
      to obtain study-specific and overall estimates of hazard ratios (with 95%
      confidence intervals), where a HR > 1 indicates that an event is more likely on
      phenytoin. MAIN RESULTS: Individual patient data were available for 480 patients
      from two trials, representing 100% of the patients recruited into the two trials
      that met our inclusion criteria. By convention, for the outcomes time to
      withdrawal of allocated treatment and time to first seizure a hazards ratio (HR)
      > 1 indicates a clinical advantage for oxcarbazepine and for time to 6 and 12
      month remission a HR > 1 indicates a clinical advantage for phenytoin. The main
      overall results (HR, 95% confidence interval (CI)) were: (i) time to withdrawal
      of allocated treatment 1.64 (1.09 to 2.47), (ii) time to 6-month remission 0.89
      (0.66 to 1.22), (iii) time to 12-month remission 0.92 (0.62 to 1.37), (iv) time
      to first seizure 1.07 (0.83 to 1.39). The overall results indicate that
      oxcarbazepine is significantly better than phenytoin for time to treatment
      withdrawal, but suggest no overall difference between oxcarbazepine and phenytoin
      for other outcomes. Results stratified by seizure type indicate no significant
      advantage for either drug for patients with generalized onset seizures, but a
      potentially important advantage in time to withdrawal for oxcarbazepine for
      patients with partial onset seizures: HR 1.92 (95% CI 1.17 to 3.16). The age
      distribution of adults classified as having generalized epilepsy suggests a
      significant number of patients may have had their epilepsy misclassified.
      AUTHORS' CONCLUSIONS: For patients with partial onset seizures oxcarbazepine is
      significantly less likely to be withdrawn, but current data do not allow a
      statement as to whether oxcarbazepine is equivalent, superior or inferior to
      phenytoin in terms of seizure control. Guidelines recommend carbamazepine as a
      first line treatment for patients with partial onset seizures and more evidence
      is needed regarding the comparative effects of oxcarbazepine and carbamazepine to
      further inform policy. For patients with generalized onset tonic-clonic seizures,
      valproate is considered the first line standard treatment and the results of this
      review do not inform current treatment policy. Misclassification of patients'
      epilepsy type may have confounded the results of this review.

PMID- 16625588
TI  - Percutaneous needle aspiration, injection, and reaspiration with or without
      benzimidazole coverage for uncomplicated hepatic hydatid cysts.
AB  - BACKGROUND: Hepatic hydatid cyst is an important public health problem in parts
      of the world where dogs are used for cattle breeding. Management of uncomplicated
      hepatic hydatid cysts is currently surgical. However, the puncture, aspiration,
      injection, and re-aspiration (PAIR) method with or without benzimidazole coverage
      has appeared as an alternative to surgery over the past decade. OBJECTIVES: To
      assess the benefits and harms of PAIR with or without benzimidazole coverage for
      patients with uncomplicated hepatic hydatid cyst in comparison with sham/no
      intervention, surgery, or medical treatment. SEARCH STRATEGY: The Cochrane Hepato
      Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register
      in The Cochrane Library, MEDLINE, EMBASE, DARE, and ACP Journal Club and full
      text searches were combined (all searched October 2004). Reference lists of
      pertinent studies and other identified literature were scanned. Researchers in
      the field were contacted. SELECTION CRITERIA: Only randomised clinical trials
      using the PAIR method with or without benzimidazole coverage as the experimental
      treatment of uncomplicated hepatic hydatid cyst (ie, hepatic hydatid cysts which
      are not infected and do not have any communication with the biliary tree or other
      viscera) versus no intervention, sham puncture (ie, performing all steps for
      puncture, pretending that PAIR is being performed, but actually not performing
      the procedure proper), surgery, or chemotherapy were included. DATA COLLECTION
      AND ANALYSIS: Data were independently extracted and methodological quality of
      each trial was assessed by the authors. Principal authors of the trials were
      contacted to retrieve missing data. MAIN RESULTS: We found no randomised clinical
      trials comparing PAIR versus no or sham intervention. We identified only two
      randomised clinical trials, one comparing PAIR versus surgical treatment (n = 50)
      and the other comparing PAIR (with or without albendazole) versus albendazole
      alone (n = 30). Both trials were graded as 'adequate' for allocation concealment;
      however, generation of allocation sequence and blinding methods were 'unclear' in
      both of them. Compared to surgery, PAIR plus albendazole obtain similar cyst
      disappearance and mean cyst diameter with fewer adverse events (32% versus 84%, P
      < 0.001) and fewer days in hospital (mean + SD) ( 4.2 + 1.5 versus 12.7 + 6.5
      days, P < 0.001). Compared to albendazole, PAIR with or without albendazole
      obtain significantly more often (P < 0.01) cyst reduction and symptomatic relief.
      AUTHORS' CONCLUSIONS: PAIR seems promising, but there is insufficient evidence to
      support or refute PAIR with or without benzimidazole coverage for treating
      patients with uncomplicated hepatic hydatid cyst. Further well-designed
      randomised clinical trials are necessary to address the topic.

PMID- 16625589
TI  - Surgical approach to hysterectomy for benign gynaecological disease.
AB  - BACKGROUND: There are three approaches to hysterectomy for benign disease -
      abdominal hysterectomy (AH), vaginal hysterectomy (VH) and laparoscopic
      hysterectomy (LH). Laparoscopic hysterectomy has three further subdivisions -
      laparoscopic assisted vaginal hysterectomy (LAVH) where a vaginal hysterectomy is
      assisted by laparoscopic procedures that do not include uterine artery ligation,
      laparoscopic hysterectomy (which we will abbreviate to LH(a)) where the
      laparoscopic procedures include uterine artery ligation, and total laparoscopic
      hysterectomy (TLH) where there is no vaginal component and the vaginal vault is
      sutured laparoscopically. OBJECTIVES: To assess the most appropriate surgical
      approach to hysterectomy. SEARCH STRATEGY: We searched the Cochrane Menstrual
      Disorders & Subfertility Group's Specialised Register of controlled trials
      (searched 23 March 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE
      (1966 to Mar 2004), EMBASE (1985 to Mar 2004), Biological Abstracts (1968 to Mar
      2004), the National Research Register and relevant citation lists. SELECTION
      CRITERIA: Only randomised trials comparing one surgical approach to hysterectomy
      with another were included. DATA COLLECTION AND ANALYSIS: Twenty-seven trials
      that included 3643 participants were included. Independent selection of trials
      and data extraction were employed following Cochrane guidelines. MAIN RESULTS:
      The benefits of VH versus AH were shorter duration of hospital stay (WMD 1.0 day,
      95%CI 0.7 to 1.2 days), speedier return to normal activities (WMD 9.5 days, 95%CI
      6.4 to 12.6 days), fewer unspecified infections or febrile episodes (OR 0.42,
      95%CI 0.21 to 0.83). The benefits of LH versus AH were lower intraoperative
      bloodloss (WMD 45.3 mls, 95%CI 17.9 to 72.7 mls) and a smaller drop in
      haemoglobin level (WMD 0.55g/L, 95%CI 0.28 to 0.82g/L), shorter duration of
      hospital stay (WMD 2.0 days, 95%CI 1.9 to 2.2 days), speedier return to normal
      activities (WMD 13.6 days, 95%CI 11.8 to 15.4 days), fewer wound or abdominal
      wall infections (OR 0.32, 95%CI 0.12 to 0.85), fewer unspecified infections or
      febrile episodes (OR 0.65, 95%CI 0.49 to 0.87), at the cost of longer operating
      time (WMD 10.6 minutes, 95%CI 7.4 to 13.8 minutes) and more urinary tract
      (bladder or ureter) injuries (OR 2.61, 95%CI 1.22 to 5.60). There was no evidence
      of benefits of LH versus VH and the operating time was increased (WMD 41.5
      minutes, 95%CI 33.7 to 49.4 minutes). There was no evidence of benefits of LH(a)
      versus LAVH and the operating time was increased for LH(a) (WMD 25.3 minutes,
      95%CI 10.0 to 40.6 minutes). There was statistical heterogeneity in many of the
      outcome measures when randomised trials were pooled for meta-analysis. No other
      statistically significant differences were found. However, for some important
      outcomes, the analyses were underpowered to detect important differences, or they
      were simply not reported in trials. Data were notably absent for many important
      long-term outcome measures. AUTHORS' CONCLUSIONS: Significantly improved outcomes
      suggest VH should be performed in preference to AH where possible. Where VH is
      not possible, LH may avoid the need for AH, however the length of the surgery
      increases as the extent of the surgery performed laparoscopically increases,
      particularly when the uterine arteries are divided laparoscopically and
      laparoscopic approaches require greater surgical expertise. The surgical approach
      to hysterectomy should be decided by a woman in discussion with her surgeon in
      light of the relative benefits and hazards. Further research is required with
      full reporting of all relevant outcomes, particularly important long-term
      outcomes, in large RCTs, to minimise the possibility of reporting bias. Further
      research is also required to define the role of the newer approaches to
      hysterectomy such as TLH.

PMID- 16625590
TI  - Glutamatergic drugs for schizophrenia.
AB  - BACKGROUND: It has been shown that central nervous system dopamine can play a
      major role in the pathophysiology of schizophrenia. Brain glutamate is thought to
      mediate symptoms in schizophrenia due to the influence of glutamate neurons on
      the dopaminergic transmission in the brain. It might be possible to decrease
      negative symptoms and the cognitive impairment of people with schizophrenia by
      treatment with glutamatergic drugs. OBJECTIVES: To determine the efficacy of
      glutamatergic drugs in the treatment of schizophrenia. SEARCH STRATEGY: We
      searched the Cochrane Schizophrenia Group's Trials Register (May 2002 and October
      2003), inspected references of all identified studies and contacted relevant
      authors. SELECTION CRITERIA: We included all randomised controlled trials in
      which glutamatergic medication was administered to people with schizophrenia.
      DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them
      and extracted data. For dichotomous data, we estimated relative risks (RR), with
      the 95% confidence intervals (CI). Where possible, we calculated the number
      needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis. MAIN
      RESULTS: We included eighteen short-term trials with 358 randomised participants.
      The single studies were small with numbers of participants ranging between six
      and 51. All trials were short-term trials with a maximum duration of 12 weeks. In
      all of these trials, glycine, D-serine, D-cycloserine, or ampakine CX516 was used
      to augment the effect of antipsychotic drugs. D-cycloserine, a partial agonist of
      NMDA receptors' glycine site, seemed ineffective towards the symptoms of
      schizophrenia. NMDA receptor co-agonists glycine and D-serine showed some effects
      in reducing the negative symptoms of schizophrenia (n=132, SMD -0.66, CI -1.0 to 
      0.3, p=0.0004), but the magnitude of the effect was moderate. Furthermore, when
      responder rates rather than mean scores of negative symptoms were analysed the
      data were inconsistent: There was no difference in responder rates between
      glycine and the control in terms of more than 20% improvement of negative
      symptoms (n=62, RR 0.70, CI 0.3 to 1.71) and only a borderline significant
      superiority in terms of more than 50% improvement (n=62, RR 0.87, CI 0.8 to
      1.00). There were also some effects in favour of glycine and/or D-serine in terms
      of overall and general symptoms, but the results were again inconsistent and
      depended on the response definition applied. Available rating scale data on
      positive symptoms and cognitive functioning did not indicate a statistically
      significant effect of glycine or D-serine. AUTHORS' CONCLUSIONS: In general, all
      glutamatergic drugs appeared to be ineffective in further reducing positive
      symptoms of the disease when added to the existing antipsychotic treatment.
      Glycine and D-serine may somewhat improve negative symptoms when added to regular
      antipsychotic medication, but the results were not fully consistent and data are
      too few to allow any firm conclusions. Many participants in the included trials
      were treatment-resistant which may have reduced treatment response. Additional
      research on glutamatergic mechanisms of schizophrenia is needed.

PMID- 16625591
TI  - Insecticide-treated nets for preventing malaria in pregnancy.
AB  - BACKGROUND: Malaria in pregnancy is associated with adverse consequences for
      mother and fetus. Protection with insecticide-treated nets (ITNs) during
      pregnancy is widely advocated, but evidence of their benefit has been
      inconsistent. OBJECTIVES: To compare the impact of ITNs with no nets or untreated
      nets on preventing malaria in pregnancy. SEARCH STRATEGY: We searched the
      Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL
      (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to January 2006), EMBASE
      (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We
      also contacted researchers working in the field. SELECTION CRITERIA: Individual
      and cluster randomized controlled trials of ITNs in pregnant women. DATA
      COLLECTION AND ANALYSIS: Three authors independently assessed trials for
      methodological quality and extracted data. Data were combined using the generic
      inverse variance method. MAIN RESULTS: Six randomized controlled trials were
      identified, five of which met the inclusion criteria: four trials from sub
      Saharan Africa compared ITNs with no nets, and one trial from Asia compared ITNs
      with untreated nets. Two trials randomized individual women and three trials
      randomized communities. In Africa, ITNs, compared with no nets, reduced placental
      malaria in all pregnancies (relative risk (RR) 0.79, 95% confidence interval (CI)
      0.63 to 0.98). They also reduced low birthweight (RR 0.77, 95% CI 0.61 to 0.98)
      and stillbirths/abortions in the first to fourth pregnancy (RR 0.67, 95% CI 0.47
      to 0.97), but not in women with more than four previous pregnancies. For anaemia
      and clinical malaria, results tended to favour ITNs, but the effects were not
      significant. In Thailand, one trial randomizing individuals to ITNs or untreated
      nets showed a significant reduction in anaemia and stillbirths/abortions in all
      pregnancies but not for clinical malaria or low birthweight. AUTHORS'
      CONCLUSIONS: ITNs have a beneficial impact on pregnancy outcome in malaria
      endemic regions of Africa when used by communities or by individual women. No
      further trials of ITNs in pregnancy are required in sub-Saharan Africa. Further
      evaluation of the potential impact of ITNs is required in areas with less intense
      and Plasmodium vivax transmission in Asia and Latin America.

PMID- 16625592
TI  - Eradication therapy for peptic ulcer disease in Helicobacter pylori positive
      patients.
AB  - BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of
      patients. 95% of duodenal and 70% of gastric ulcers are associated with
      Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers
      but the magnitude of this effect is uncertain. OBJECTIVES: The primary outcomes
      were the proportion of peptic ulcers healed initially and proportion of patients
      free from relapse following successful healing. Eradication therapy was compared
      to placebo or pharmacological therapies in H. pylori positive patients. Secondary
      aims included symptom relief and adverse effects. SEARCH STRATEGY: Searches were
      conducted on the Cochrane Central register of Controlled Trials - CENTRAL (which
      includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials
      Register) on The Cochrane Library (Issue 3 2002) MEDLINE (1966 to July 2002) and
      EMBASE (1980 to July 2002). Reference lists from trials selected by electronic
      searching were handsearched to identify further relevant trials. Published
      abstracts from conference proceedings from the United European Gastroenterology
      Week (published in Gut) and Digestive Disease Week (published in
      Gastroenterology) were handsearched. The search was updated in September 2003,
      November 2004 and November 2005. Members of the Cochrane UGPD Group, and experts
      in the field were contacted and asked to provide details of outstanding clinical
      trials and any relevant unpublished materials SELECTION CRITERIA: Randomised
      controlled trials of short and long-term treatment of peptic ulcer disease in H.
      pylori positive adults were analysed. Patients received at least one week of H
      pylori eradication compared with ulcer healing drug, placebo or not treatment.
      Trials were included if they reported assessment from 2 weeks onwards. DATA
      COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief
      of symptoms and adverse effects. MAIN RESULTS: 63 trials were eligible. Data
      extraction was not possible in 7 trials, and 56 trials were included. In duodenal
      ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34
      trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95%
      confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients,
      RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant
      differences were detected between eradication therapy and UHD (14 trials, 1572
      patients, RR = 1.25; 95% CI = 0.88, 1.76). In preventing duodenal ulcer
      recurrence no significant differences were detected between eradication therapy
      and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of
      ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was
      superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15,
      0.26). In preventing gastric ulcer recurrence, eradication therapy was superior
      to no treatment (11 trials, 1104 patients, RR = 0.29; 95% CI 0.20, 0.42).
      AUTHORS' CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is
      an effective treatment for H. pylori positive peptic ulcer disease.

PMID- 16625593
TI  - Surgery versus medical therapy for heavy menstrual bleeding.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) significantly impairs the quality of
      life of many otherwise healthy women. Perception of HMB is subjective and
      management usually depends upon what symptoms are acceptable to the individual.
      Medical treatment options include oral medication and a hormone-releasing
      intrauterine system (LNG-IUS). Surgical options include conservative surgery
      (uterine resection or ablation) and hysterectomy. OBJECTIVES: To compare the
      effectiveness, safety and acceptability of surgery versus medical therapy for
      HMB. SEARCH STRATEGY: In September 2005 we searched the Cochrane Menstrual
      Disorders and Subfertility Group trials register Cochrane Controlled Trials
      Register (The Cochrane Library Issue 3, 2005), MEDLINE EMBASE, Current Contents,
      Biological Abstracts, PsycINFO, and CINAHL. We also searched reference lists of
      articles retrieved and contacted pharmaceutical companies and experts in the
      field. SELECTION CRITERIA: Controlled randomised trials comparing conservative
      surgery or hysterectomy versus medical therapy (oral or intrauterine) for HMB
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for
      quality and extracted data . MAIN RESULTS: The eight included trials randomised
      821 women. In comparisons of oral medication versus surgery, 58% of women
      randomised to medical treatment had received surgery by two years. Compared to
      oral medication, endometrial resection was significantly more effective in
      controlling bleeding (at four months: OR 10.62, 95% CI 5.30 to 21.27) and
      significantly less likely to cause side effects (at four months: OR 0.15, 95% CI
      0.07 to 0.31) and hysterectomy resulted in significantly greater improvements in
      mental health (at six months p = 0.04). In comparisons of LNG-IUS versus
      conservative surgery or hysterectomy, at one year there was no statistically
      significant difference in satisfaction rates or quality of life, though adverse
      effects were significantly less likely with conservative surgery (OR 0.24, 95% CI
      0.11 to 0.49). Two trials found conservative surgery significantly more effective
      than LNG-IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38).
      Two other small trials with longer follow-up found no difference or favoured LNG
      IUS - however in both these studies the data were skewed and fewer than two
      thirds of participants were analysed. Hysterectomy stopped all bleeding but
      caused serious complications for some women. AUTHORS' CONCLUSIONS: Surgery,
      especially hysterectomy, reduces menstrual bleeding at one year more than medical
      treatments but LNG-IUS appears equally effective in improving quality of life.
      The evidence for longer term comparisons is weak and inconsistent. Oral
      medication suits a minority of women long term.

PMID- 16625594
TI  - Compression stockings for preventing deep vein thrombosis in airline passengers.
AB  - BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It
      has been suggested that wearing compression stockings might reduce this risk.
      OBJECTIVES: To assess the effects of wearing compression stockings versus not
      wearing them among people travelling on flights lasting at least four hours.
      SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group's
      Specialized Register (January 2006), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (in The Cochrane Library, Issue 4, 2005), MEDLINE (January 1966
      to November 2005), EMBASE (January 1980 to December 2005) and several other
      electronic or grey literature sources, detailed in full in the review. The most
      recent searches were done in January 2006. SELECTION CRITERIA: Randomized trials
      of compression stockings versus no stockings in passengers on flights lasting at
      least four hours. Trials in which passengers wore a stocking on one leg but not
      the other, or those comparing stockings and another intervention were also
      eligible. DATA COLLECTION AND ANALYSIS: At least two authors independently
      assessed the quality of each study and extracted data. We sought additional
      information from trialists. MAIN RESULTS: Ten randomized trials (n = 2856) were
      included; nine (n = 2821) compared wearing stockings on both legs versus not
      wearing them, and one (n = 35) compared wearing a stocking on one leg for the
      outbound flight and on the other leg on the return flight. Of the nine trials,
      seven included people judged to be at low or medium risk (n = 1548) and two
      included high risk participants (n = 1273). All flights lasted at least seven
      hours. Fifty of 2637 participants with follow-up data available in the trials of
      wearing stockings on both legs had a symptomless DVT; three wore stockings, 47
      did not (odds ratio 0.10, 95% confidence interval 0.04 to 0.25, P < 0.00001).
      There were no symptomless DVTs in three trials. No deaths, pulmonary emboli or
      symptomatic DVTs were reported. Wearing stockings had a significant impact in
      reducing oedema (based on six trials). No significant adverse effects were
      reported. AUTHORS' CONCLUSIONS: Airline passengers similar to those in this
      review can expect a substantial reduction in the incidence of symptomless DVT and
      leg oedema if they wear compression stockings. We cannot assess the effect of
      wearing stockings on death, pulmonary embolus or symptomatic DVT because no such
      events occurred in these trials. Randomized trials to assess these outcomes would
      need to include a very large number of people.

PMID- 16625595
TI  - The effects of blood pressure lowering on development of cognitive impairment and
      dementia in patients without apparent prior cerebrovascular disease.
AB  - BACKGROUND: Hypertension and cognitive impairment are prevalent in older people.
      It is known that hypertension is a direct risk factor for vascular dementia and
      recent studies have suggested hypertension also impacts upon prevalence of
      Alzheimer's disease. The question is therefore whether treatment of hypertension
      lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood
      pressure lowering treatments for the prevention of dementia and cognitive decline
      in patients with hypertension but no history of cerebrovascular disease. SEARCH
      STRATEGY: The trials were identified through a search of CDCIG's Specialised
      Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005.
      SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which
      pharmacological or non-pharmacological interventions to lower blood pressure were
      given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers assessed trial quality and extracted data. The following outcomes were
      assessed: incidence of dementia, cognitive change from baseline, blood pressure
      level, incidence and severity of side effects and quality of life. MAIN RESULTS:
      Three trials including 12,091 hypertensive subjects were identified. Average age
      was 72.8 years. Participants were recruited from industrialised countries. Mean
      blood pressure at entry across the studies was 170/84 mmHg. All trials instituted
      a stepped care approach to hypertension treatment, starting with a calcium
      channel blocker, a diuretic or an angiotensin receptor blocker. The combined
      result of the three trials reporting incidence of dementia indicated no
      significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95%
      CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk
      reduction of dementia in patients with no prior cerebrovascular disease but this
      effect was not statistically significant (p = 0.38) and there was considerable
      heterogeneity between the trials. The combined results from the two trials
      reporting change in Mini Mental State Examination (MMSE) did not indicate a
      benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03,
      0.23). Both systolic and diastolic blood pressure levels were reduced
      significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI 
      8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for
      diastolic blood pressure). Two trials reported adverse effects requiring
      discontinuation of treatment and the combined results indicated a significant
      benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately,
      however, more patients on placebo in SCOPE were likely to discontinue treatment
      due to side effects; the converse was true in SHEP 1991. Quality of life data
      could not be analysed in the three studies. There was difficulty with the control
      group in this review as many of the control subjects received antihypertensive
      treatment because their blood pressures exceeded pre-set values. In most cases
      the study became a comparison between the study drug against a usual
      antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence
      from the trials identified that blood pressure lowering prevents the development
      of dementia or cognitive impairment in hypertensive patients with no apparent
      prior cerebrovascular disease. There were significant problems identified with
      analysing the data, however, due to the number of patients lost to follow-up and
      the number of placebo patients given active treatment. This introduced bias. More
      robust results may be obtained by analysing one year data to reduce differential
      drop-out or by conducting a meta-analysis using individual patient data.

PMID- 16625596
TI  - Preoperative hair removal to reduce surgical site infection.
AB  - BACKGROUND: The preparation of people for surgery has traditionally included the
      routine removal of body hair from the intended surgical wound site. However,
      there are studies which claim that pre-operative hair removal is deleterious to
      patients, perhaps by causing surgical site infections (SSIs), and should not be
      carried out. OBJECTIVES: The primary objective of this review was to determine if
      routine pre-operative hair removal results in fewer SSIs than not removing hair.
      SEARCH STRATEGY: The reviewers searched the Cochrane Wounds Group Specialised
      Register (October 2005), The Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 3, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005),
      CINAHL (1982 to 2005), and the ZETOC database of conference proceedings (1993 to
      2005). We also contacted manufacturers of hair removal products. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing hair removal with no hair
      removal, different methods of hair removal, hair removal conducted at different
      times prior to surgery and hair removal carried out in different settings. DATA
      COLLECTION AND ANALYSIS: Three authors independently assessed the relevance and
      quality of each trial. Data was extracted independently by one author and cross
      checked for accuracy by a second author. MAIN RESULTS: Eleven RCTs were included
      in this review. Three trials involving 625 people compared hair removal using
      either depilatory cream or razors with no hair removal and found no statistically
      significant difference between the groups in terms of surgical site infections.
      No trials were identified which compared clipping with no hair removal. Three
      trials involving 3193 people compared shaving with clipping and found that there
      were statistically significantly more SSIs when people were shaved rather than
      clipped (RR 2.02, 95%CI 1.21 to 3.36). Seven trials involving 1420 people
      compared shaving with removing hair using a depilatory cream but found no
      statistically significant difference between the two groups in SSI rates. No
      trials were found that compared clipping with a depilatory cream.One trial
      involving 537 people compared shaving on the day of surgery with shaving the day
      before surgery and one trial compared clipping on the day of surgery with
      clipping the day before surgery; neither trial found a statistically significant
      difference in the number of SSIs. No trials were found that compared depilatory
      cream at different times or that compared hair removal in different settings.
      AUTHORS' CONCLUSIONS: The evidence finds no difference in SSIs among patients who
      have had hair removed prior to surgery and those who have not. If it is necessary
      to remove hair then clipping results in fewer SSIs than shaving using a razor.
      There is insufficient evidence regarding depilatory cream compared with shaving
      using a razor. There is no difference in SSIs when patients are shaved or clipped
      one day before surgery or on the day of surgery.

PMID- 16625597
TI  - Marital therapy for depression.
AB  - BACKGROUND: Marital therapy for depression has the two-fold aim of modifying
      negative interaction patterns and increasing mutually supportive aspects of
      couple relationships, thus changing the interpersonal context linked to
      depression. OBJECTIVES: 1. To conduct a meta-analysis of all intervention studies
      comparing marital therapy to other psychosocial and pharmacological treatments,
      or to non-active treatments. 2. To conduct an assessment of the internal validity
      and external validity. 3. To assess the overall effectiveness of marital therapy
      as a treatment for depression. 4. To identify mediating variables through which
      marital therapy is effective in depression treatment. SEARCH STRATEGY: CCDANCTR
      Studies was searched on 5-9-2005, Relevant journals and reference lists were
      checked. SELECTION CRITERIA: Randomised controlled trials examining the
      effectiveness of marital therapy versus individual psychotherapy, drug therapy or
      waiting list/no treatment/minimal treatment for depression were included in the
      review. Quasi-randomised controlled trials were also included. DATA COLLECTION
      AND ANALYSIS: Data were extracted using a standardised spreadsheet. Where data
      were not included in published papers, two attempts were made to obtain the data
      from the authors. Data were synthesised using Review Manager software.
      Dichotomous data were pooled using the relative risk (RR), and continuous data
      were pooled using the standardised mean difference (SMD), and 95% confidence
      intervals (CIs) were calculated. The random effects model was employed for all
      comparisons. A formal test for heterogeneity, the natural approximate chi-squared
      test, was also calculated. MAIN RESULTS: Eight studies were included in the
      review. No significant difference in effect was found between marital therapy and
      individual psychotherapy, either for the continuous outcome of depressive
      symptoms, based on six studies: SMD -0.12 (95% CI -0.56 to 0.32), or the
      dichotomous outcome of proportion of subjects remaining at caseness level, based
      on three studies: RR 0.84 (95% CI 0.32 to 2.22). In comparison with drug therapy,
      a lower drop-out rate was found for marital therapy: RR 0.31 (95% CI 0.15 to
      0.61), but this result was greatly influenced by a single study. The comparison
      with no/minimal treatment, showed a large significant effect in favour of marital
      therapy for depressive symptoms, based on two studies: SMD -1.28 (95% CI -1.85 to
      -0.72) and a smaller significant effect for persistence of depression, based on
      one study only. The findings were weakened by methodological problems affecting
      most studies, such as the small number of cases available for analysis in almost
      all comparisons, and the significant heterogeneity among studies. AUTHORS'
      CONCLUSIONS: There is no evidence to suggest that marital therapy is more or less
      effective than individual psychotherapy or drug therapy in the treatment of
      depression. Improvement of relations in distressed couples might be expected from
      marital therapy. Future trials should test whether marital therapy is superior to
      other interventions for distressed couples with a depressed partner, especially
      considering the role of potential effect moderators in the improvement of
      depression.

PMID- 16625598
TI  - Palliative biliary stents for obstructing pancreatic carcinoma.
AB  - BACKGROUND: Palliative endoscopic stents or surgical by-pass are often required
      for inoperable pancreatic carcinoma to relieve symptomatic obstruction of the
      distal biliary tree. The optimal method of intervention remains unknown.
      OBJECTIVES: To compare surgery, metal endoscopic stents and plastic endoscopic
      stents in the relief of distal biliary obstruction in patients with inoperable
      pancreatic carcinoma. SEARCH STRATEGY: We searched the databases of the Cochrane
      Upper Gastrointestinal and Pancreatic Group specialised register, Cochrane
      Central Register of Controlled Trials, MEDLINE, EMBASE, CancerLit, Current
      Concepts Database and BIDS (September 2002 to September 2004). The searches were
      re-run in December 2005 and we are awaiting further details on two trials.
      Reference lists of articles and published abstracts from UEGW and DDW were hand
      searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      surgery to endoscopic stenting, endoscopic metal stents to plastic stents, and
      different types of endoscopic plastic and metal stents, used to relieve
      obstruction of the distal bile duct in patients with inoperable pancreatic
      carcinoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial
      quality and extracted data. Adverse effects information was collected from the
      trials. MAIN RESULTS: Twenty-one trials involving 1,454 people were included.
      Based on meta-analysis, endoscopic stenting with plastic stents appears to be
      associated with a reduced risk of complications (RR 0.60, 95% CI 0.45 - 0.81),
      but with higher risk of recurrent biliary obstruction prior to death (RR 18.59,
      95% CI 5.33 - 64.86) when compared with surgery. There was a trend towards higher
      30-day mortality in the surgical group (p=0.07, RR 0.58, 95% CI 0.32, 1.04).
      There was no evidence of a difference in technical or therapeutic success. Other
      outcomes were not suitable for meta-analysis. No trials comparing endoscopic
      metal stents to surgery were identified. In endoscopic stent comparisons, metal
      biliary stents appear to have a lower risk of recurrent biliary obstruction than
      plastic stents (RR 0.52, 95% CI 0.39 - 0.69). There was no significant
      statistical difference in technical success, therapeutic success, complications
      or 30-day mortality using meta-analysis. A narrative review of studies of the
      cost-effectiveness of metal stents drew conflicting conclusions, but results may
      be dependent on the patients' length of survival.Neither Teflon, hydrourethane,
      or hydrophilic coating appear to improve the patency of plastic stents above
      polyethylene in the trials reviewed. Only perflouro alkoxy plastic stents had
      superior outcome to polyethylene stents in one trial. The single eligible trial
      comparing types of metal stents reported higher patency with covered stents, but
      also a higher risk of complications. These results are based on review of the
      trials individual results only. AUTHORS' CONCLUSIONS: Endoscopic metal stents are
      the intervention of choice at present in patients with malignant distal
      obstructive jaundice due to pancreatic carcinoma. In patients with short
      predicted survival, their patency benefits over plastic stents may not be
      realised. Further RCTs are needed to determine the optimal stent type for these
      patients.

PMID- 16625599
TI  - Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary
      immunosuppression in kidney transplant recipients.
AB  - BACKGROUND: Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are
      immunosuppressive agents with a novel mode of action but an uncertain clinical
      role. OBJECTIVES: To investigate the benefits and harms of immunosuppressive
      regimens containing TOR-I when compared to other regimens as initial therapy for
      kidney transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005),
      MEDLINE (1966-June 2005), EMBASE (1980-June 2005), the specialised register of
      the Cochrane Renal Group (June 2005)., and contacted authors and pharmaceutical
      companies to identify relevant studies. SELECTION CRITERIA: All randomised
      controlled trials (RCTs) and quasi-RCTs where drug regimens containing TOR-I were
      compared to alternative drug regimens in the immediate post-transplant period
      were included, without age restriction, dosage or language of report. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for
      eligibility and quality, and extracted data. Results are expressed as relative
      risk (RR) or weight mean difference (MD) with 95% confidence intervals (CI). MAIN
      RESULTS: Thirty three trials (142 reports) were included (sirolimus (27),
      everolimus (5), head-to-head (1)). When TOR-I replaced CNI there was no
      difference in acute rejection, but serum creatinine was lower (MD -18.31
      micromol/L, -30.96 to -5.67), and bone marrow more suppressed (leucopenia: RR
      2.02 1.12 to 3.66; thrombocytopenia: RR 6.97 2.97 to 16.36; anaemia: RR 1.67,
      1.27 to 2.20). When TOR-I replaced antimetabolites, acute rejection (RR 0.84,
      0.71 to 0.99) and cytomegalovirus infection (CMV) (RR 0.49; 0.37 to 0.65) were
      reduced, but hypercholesterolaemia was increased (RR 1.65, 1.32 to 2.06). For low
      versus high-dose TOR-I, with equal CNI dose, rejection was increased (RR 1.23,
      1.06 to 1.43) but calculated GFR higher (MD 4.27 mL/min, 1.12 to 7.41), and for
      low-dose TOR-I/standard-dose CNI versus higher-dose TOR-I/reduced CNI, acute
      rejection (RR 0.67, 0.52 to 0.88) and calculated GFR (MD -9.46 mL/min, -12.16 to 
      6.76) were reduced. There was no significant difference in mortality, graft loss
      or malignancy risk for TOR-I in any comparison. AUTHORS' CONCLUSIONS: TOR-I have
      been evaluated in four different primary immunosuppressive algorithms; as
      replacement for CNI and for antimetabolites, in combination with CNI at low and
      high dose and with variable dose of CNI. Generally, surrogate endpoints for graft
      survival favour TOR-I (lower risk of acute rejection and higher GFR) and
      surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow
      suppression, lipid disturbance). Long-term hard-endpoint data from
      methodologically robust RCTs are still needed.

PMID- 16625600
TI  - Short term urinary catheter policies following urogenital surgery in adults.
AB  - BACKGROUND: Urinary catheterisation (by the urethral or suprapubic routes) is
      common following urogenital surgery. There is no consensus on how to minimize
      complications and practice varies. OBJECTIVES: To establish the optimal way to
      manage urinary catheters following urogenital surgery in adults. SEARCH STRATEGY:
      We searched the Cochrane Incontinence Group specialised trials register (searched
      30 May 2005) and the reference lists of relevant articles. SELECTION CRITERIA:
      Randomised and quasi-randomised trials were identified. Studies were excluded if
      they were not randomised or quasi-randomised trials of adults being catheterised
      following urogenital surgery. DATA COLLECTION AND ANALYSIS: Data collection was
      performed independently by two of the review authors and cross-checked. Where
      data might have been collected but not reported, clarification was sought from
      the trialists. MAIN RESULTS: Thirty nine randomised trials were identified for
      inclusion in the review. They were generally small and of poor or moderate
      quality reporting data on only few outcomes. Confidence intervals were all wide.
      USING A URINARY CATHETER VERSUS NOT USING ONE: The data from five trials were
      heterogeneous but tended to indicate a higher risk of (re)catheterisation if a
      catheter was not used postoperatively. The data gave only an imprecise estimate
      of any difference in urinary tract infection. URETHRAL CATHETERISATION VERSUS
      SUPRAPUBIC CATHETERISATION: In six trials, a greater number of people needed to
      be recatheterised if a urethral catheter rather than a suprapubic one was used
      following surgery (RR 3.66, 95% CI 1.41 to 9.49). SHORTER POSTOPERATIVE DURATION
      OF CATHETER USE VERSUS LONGER DURATION: In 11 trials, the seven trials with data
      suggested fewer urinary tract infections when a catheter was removed earlier (for
      example 1 versus 3 days, RR 0.50, 95% CI 0.29 to 0.87) with no pattern in respect
      of catheterisation. CLAMP AND RELEASE POLICIES BEFORE CATHETER REMOVAL VERSUS
      IMMEDIATE CATHETER REMOVAL: In a single small trial, the clamp-and-release group
      showed a significantly greater incidence of urinary tract infections (RR 4.00,
      95% 1.55 to 10.29) and a delay in return to normal voiding (RR 2.50, 95% CI 1.16
      to 5.39). AUTHORS' CONCLUSIONS: Despite reviewing 39 eligible trials, few firm
      conclusions could be reached because of the multiple comparisons considered, the
      small size of individual trials, and their low quality. Whether or not to use a
      particular policy is usually a trade-off between the risks of morbidity
      (especially infection) and risks of recatheterisation.

PMID- 16625601
TI  - Music therapy for autistic spectrum disorder.
AB  - BACKGROUND: The central impairments of people with autistic spectrum disorder
      (ASD) include social interaction and communication. Music therapy uses music and
      its elements to enable communication and expression, thus attempting to address
      some of the core problems of people with ASD. OBJECTIVES: To review the effects
      of music therapy for individuals with autistic spectrum disorders. SEARCH
      STRATEGY: The following databases were searched: CENTRAL, 2005, (Issue 3);
      Medline, (1966 to July 2004); Embase, (1980 to July 2004); LILACS, (1982 to July
      2004); PsycINFO, (1872 to July 2004); CINAHL, (1982 to July 2004); ERIC, (1966 to
      July 2004); ASSIA, (1987 to July 2004); Sociofile, (1963 to July 2004);
      Dissertation Abstracts International, (late 1960's to July 2004). These searches
      were supplemented by searching specific sources for music therapy literature and
      manual searches of reference lists. Personal contacts to some investigators were
      made. SELECTION CRITERIA: All randomised controlled trials or controlled clinical
      trials comparing music therapy or music therapy added to standard care to
      "placebo" therapy, no treatment or standard care. DATA COLLECTION AND ANALYSIS:
      Studies were independently selected, quality assessed and data extracted by two
      authors. Continuous outcomes were synthesised using a standardised mean
      difference (SMD) in order to enable a meta-analysis combining different scales,
      and to facilitate the interpretation of effect sizes. Heterogeneity was assessed
      using the I(2) statistic. MAIN RESULTS: Three small studies were included (total
      n = 24). These examined the short-term effect of brief music therapy
      interventions (daily sessions over one week) for autistic children. Music therapy
      was superior to "placebo" therapy with respect to verbal and gestural
      communicative skills (verbal: 2 RCTs, n = 20, SMD 0.36 CI 0.15 to 0.57; gestural:
      2 RCTs, n = 20, SMD 0.50 CI 0.22 to 0.79). Effects on behavioural problems were
      not significant. AUTHORS' CONCLUSIONS: The included studies were of limited
      applicability to clinical practice. However, the findings indicate that music
      therapy may help children with autistic spectrum disorder to improve their
      communicative skills. More research is needed to examine whether the effects of
      music therapy are enduring, and to investigate the effects of music therapy in
      typical clinical practice.

PMID- 16625602
TI  - Antibiotics for exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Most patients with an exacerbation of chronic obstructive pulmonary
      disease (COPD) are treated with antibiotics. However the value of their use
      remains uncertain. Some controlled trials of antibiotics have shown benefit
      (Berry 1960; Pines 1972) while others have not (Elmes 1965b; Nicotra 1982).
      OBJECTIVES: To conduct a systematic review of the literature estimating the value
      of antibiotics in the management of acute COPD exacerbations. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 4, 2005); MEDLINE (1966 to December 2005); EMBASE (1974 to
      December 2005); Web of Science (December 2005), and other electronically
      available databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) in
      patients with acute COPD exacerbations comparing antibiotic (for a minimum of
      five days) and placebo. DATA COLLECTION AND ANALYSIS: Data were analysed using
      Review Manager software. Continuous data were analysed using weighted mean
      differences (WMD) and 95% confidence intervals (CI). Relative risks (RR) (and 95%
      CI) were calculated for all dichotomous data. Where appropriate, number needed to
      treat to benefit (NNT) and 95% CI were calculated. MAIN RESULTS: Eleven trials
      with 917 patients were included. Ten trials used increased cough, sputum volume
      and purulence diagnostic criteria for COPD exacerbation. Eight-hundred and fifty
      seven patients provided data for outcomes including mortality, treatment failure,
      increased sputum volume, sputum purulence, PaCO(2), PaO(2), peak flow and adverse
      events. Antibiotic therapy regardless of antibiotic choice significantly reduced
      mortality (RR 0.23; 95% CI 0.10 to 0.52 with NNT of 8; 95% CI 6 to 17), treatment
      failure (RR 0.47; 95% CI 0.36 to 0.62 with NNT of 3; 95% CI 3 to 5) and sputum
      purulence (RR 0.56; 95% CI 0.41 to 0.77 with NNT of 8; 95% CI 6 to 17). There was
      a small increase in risk of diarrhoea with antibiotics (RR 2.86; 95% CI 1.06 to
      7.76). Antibiotics did not improve arterial blood gases and peak flow. AUTHORS'
      CONCLUSIONS: This review shows that in COPD exacerbations with increased cough
      and sputum purulence antibiotics, regardless of choice, reduce the risk of short
      term mortality by 77%, decrease the risk of treatment failure by 53% and the risk
      of sputum purulence by 44%; with a small increase in the risk of diarrhoea. These
      results should be interpreted with caution due to the differences in patient
      selection, antibiotic choice, small number of included trials and lack of control
      for interventions that influence outcome, such as use of systemic corticosteroids
      and ventilatory support. Nevertheless, this review supports antibiotics for
      patients with COPD exacerbations with increased cough and sputum purulence who
      are moderately or severely ill.

PMID- 16625603
TI  - Thrombolytic therapy for pulmonary embolism.
AB  - BACKGROUND: Thrombolytic therapy is usually reserved for patients with clinically
      serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic
      agents may dissolve blood clot more rapidly than heparin and might reduce the
      death rate associated with PE. However, there are still concerns about the
      possible risk of adverse effects of thrombolytic therapy, such as major or minor
      haemorrhages. OBJECTIVES: To assess the effectiveness and safety of thrombolytic
      therapy in patients with acute PE. SEARCH STRATEGY: We sought trials through the
      Cochrane Peripheral Vascular Diseases Group's Specialised Register (January 18,
      2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 1, 2006), MEDLINE (January 1966 to December 2004), EMBASE, CINAHL,
      LILACS and SCISEARCH (all November 2004). We also searched individual trial
      collections and private databases, along with bibliographies of relevant
      articles. Relevant medical journals were handsearched. The most recent search was
      on February 6, 2006. SELECTION CRITERIA: Randomised controlled trials that
      compared thrombolytic therapy with placebo or heparin or surgical intervention in
      patients with acute PE. We did not include trials comparing two different
      thrombolytic agents or different doses of the same thrombolytic drug. DATA
      COLLECTION AND ANALYSIS: Two authors (DB and WQ) assessed the eligibility and
      quality of trials and extracted data. MAIN RESULTS: Results were similar between
      thrombolytics compared with heparin alone or placebo and heparin in terms of:a)
      death rate: odds ratio (OR) 0.89; 95% confidence interval (CI) 0.45 to 1.78; b)
      recurrence of pulmonary embolism: OR 0.63; 95% CI 0.33 to 1.20;c) major
      haemorrhagic events: OR 1.61; 95% CI 0.91 to 2.86;d) minor haemorrhagic events:
      OR 1.98; 95% CI 0.68 to 5.75. We found no trials comparing thrombolytic therapy
      to surgical intervention. Using recombinant tissue-type plasminogen activator (rt
      PA) and heparin together compared to heparin alone appeared to reduce the need
      for further treatment for in-hospital events (OR 0.35; 95% CI 0.17 to 0.71).
      Thrombolytics improved haemodynamic outcomes, perfusion lung scanning, pulmonary
      angiogram assessment and echocardiograms to a greater extent than heparin alone.
      AUTHORS' CONCLUSIONS: We cannot conclude whether thrombolytic therapy is better
      than heparin for pulmonary embolism based on the limited evidence found. More
      double-blind RCTs, with subgroup analysis of patients presenting with
      haemodynamically stable acute pulmonary embolism compared to those patients with
      a haemodynamic unstable condition, are required.

PMID- 16625604
TI  - Capsaicin for allergic rhinitis in adults.
AB  - BACKGROUND: Allergic rhinitis represents a global health problem. Non-specific
      nasal hyperresponsiveness is an important feature of allergic and non-allergic
      rhinitis. This phenomenon is believed to result from the effect of allergic
      inflammation on the sensory nerves that supply the upper airway mucosa. A
      pharmacologic agent that has proved useful in the investigation of effects of
      neuronal stimulation is capsaicin, the pungent component of hot pepper.
      Intranasal capsaicin specifically stimulates afferent nerves consisting mostly of
      unmyelinated C fibers and some myelinated A-delta fibers. As a result it can
      trigger central and axonal reflexes, the latter being putatively mediated by the
      release of neuropeptides. Capsaicin as a blocking agent of neuropeptides, blocks
      the axon reflex and may exert a curative effect on allergic rhinitis. OBJECTIVES:
      To assess the effectiveness of capsaicin for allergic rhinitis in adults. SEARCH
      STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to 2006) and EMBASE
      (1974 to 2006). We assessed bibliographies from included studies, and contacted
      authors of known studies for additional information about published and
      unpublished trials. The date of the most recent search was January 2006.
      SELECTION CRITERIA: Randomised controlled trials of capsaicin for allergic
      rhinitis in adults were included. DATA COLLECTION AND ANALYSIS: Three reviewers
      read each paper, blind to its identity. Decisions concerning inclusion were made
      by simple majority. We all performed quality assessment independently. MAIN
      RESULTS: One small trial did not find evidence that intranasal capsaicin had a
      therapeutic effect in allergic rhinitis. A small pharmacological effect on
      clinical histamine dose response was found. After treatment, leukotriene levels
      in nasal lavage did not increase in the capsaicin group. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to assess the use of capsaicin in clinical
      practice.

PMID- 16625605
TI  - Herbal medicine for low back pain.
AB  - BACKGROUND: Low-back pain is a common condition and a substantial economic burden
      in industrialized societies. A large proportion of patients with chronic low-back
      pain use complementary and alternative medicine (CAM), visit CAM practitioners,
      or both. Several herbal medicines have been purported for use in low-back pain.
      OBJECTIVES: To determine the effectiveness of herbal medicine for non-specific
      low-back pain. SEARCH STRATEGY: We searched the following electronic databases:
      Cochrane Complementary Medicine Field Trials Register (Issue 3, 2005), MEDLINE
      (1966 to July 2005), EMBASE (1980 to July 2005); checked reference lists in
      review articles, guidelines and retrieved trials; and personally contacted
      individuals with expertise in this very specialized area. SELECTION CRITERIA: We
      included randomized controlled trials, examining adults (over 18 years of age)
      suffering from acute, sub-acute or chronic non-specific low-back pain. The
      interventions were herbal medicines, defined as plants that are used for
      medicinal purposes in any form. Primary outcome measures were pain and function.
      DATA COLLECTION AND ANALYSIS: Two authors (JJG & MVT) conducted the database
      searches. One author contacted content experts and acquired relevant citations.
      Full references and abstracts of the identified studies were downloaded. A hard
      copy was retrieved for final inclusion decisions. Methodological quality and
      clinical relevance were assessed separately by two individuals. Disagreements
      were resolved by consensus. MAIN RESULTS: Ten trials were included in this
      review. Two high quality trials examining the effects of Harpagophytum Procumbens
      (Devil's Claw) found strong evidence that daily doses standardized to 50 mg or
      100 mg harpagoside were better than placebo for short-term improvements in pain
      and rescue medication. Another high quality trial demonstrated relative
      equivalence to 12.5 mg per day of rofecoxib (Vioxx). Two trials examining the
      effects of Salix Alba (White Willow Bark) found moderate evidence that daily
      doses standardized to 120 mg or 240 mg salicin were better than placebo for short
      term improvements in pain and rescue medication. An additional trial demonstrated
      relative equivalence to 12.5 mg per day of rofecoxib. Three low quality trials on
      Capsicum Frutescens (Cayenne), examining various topical preparations, found
      moderate evidence that Capsicum Frutescens produced more favourable results than
      placebo and one trial found equivalence to a homeopathic ointment. AUTHORS'
      CONCLUSIONS: Harpagophytum Procumbens, Salix Alba and Capsicum Frutescens seem to
      reduce pain more than placebo. Additional trials testing these herbal medicines
      against standard treatments are needed. The quality of reporting in these trials
      was generally poor. Trialists should refer to the CONSORT statement extension for
      reporting trials of herbal medicine interventions.

PMID- 16625606
TI  - Stavudine, lamivudine and nevirapine combination therapy for treatment of HIV
      infection and AIDS in adults.
AB  - BACKGROUND: A favourable regimen for people infected with HIV/AIDS is one that
      provides optimal efficacy, durability of antiretroviral activity, tolerability,
      and has low adverse effects and drug-drug interactions. The combination of the
      non-nucleoside reverse transcriptase inhibitor nevirapine (NVP), and two
      nucleoside reverse transcriptase inhibitors, stavudine (d4T) and lamivudine
      (3TC), is widely used as first-line therapy, especially in low-resource
      countries. Analysis of the efficacy, durability and tolerability of the regimen
      is thus important to clinicians, consumers and policy-makers living in both rich
      and poor countries. OBJECTIVES: To examine the efficacy of the stavudine,
      lamivudine and nevirapine regimen for the treatment of HIV infection and AIDS in
      adults. SEARCH STRATEGY: We used the comprehensive search strategy developed
      specifically by the Cochrane HIV/AIDS Review Group to identify HIV/AIDS
      randomised controlled trials, and searched the following electronic databases:
      MEDLINE (searched July 2004); Embase (searched October 2004); and CENTRAL (July
      2004). This search was supplemented with a search of AIDSearch (April 2005) to
      identify relevant conference abstracts, as well as searching reference lists of
      all eligible articles. The search was not limited by language or publication
      status. SELECTION CRITERIA: Randomised controlled trials of the stavudine,
      lamivudine and nevirapine regimen, compared with any other regimens for treating
      HIV/AIDS, in antiretroviral treatment-naive or antiretroviral treatment
      experienced adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed the methodological quality of the trials and extracted data. MAIN
      RESULTS: Our search resulted in 1,148 records, of which two studies described
      trials that met our inclusion criteria. One trial was a small single-centre
      Australian trial of 70 antiretroviral-naive participants, while the other trial
      was a large, multicentre trial, conducted in 14 countries, of 1,216
      antiretroviral-naive participants. In both trials over 60% of participants were
      male. As the therapeutic combinations compared in both trials were not identical,
      it was not possible to conduct a meta-analysis to increase the power of the
      results. The main findings, therefore, are from the much larger trial, which was
      of a high quality. This trial found that there was no statistically significant
      difference in the efficacy (measured by treatment failure) between nevirapine and
      efavirenz (EFZ), when used in combination with 3TC and d4T (RR = 1.16; 95%CI:
      0.95, 1.41). There was no statistically significant difference between once daily
      or twice-daily dosing of NVP, when used in combination with 3TC and d4T (RR =
      1.00; 95%CI: 0.83; 1.21). It also showed that, compared with NVP plus EFZ, 3TC
      and d4T, a once-daily dosing of NVP, in combination with 3TC and d4T, performs
      better in averting treatment failure (RR = 0.82; 95%CI: 0.67, 1.00) than does
      twice-daily dosing of NVP with 3TC and d4T (RR = 0.82; 95%CI: 0.69; 0.97).
      Frequency of toxicity was higher in participants receiving NVP, compared with
      EFZ. AUTHORS' CONCLUSIONS: The combination of nevirapine, 3TC and d4T is as
      efficacious as a combination of efavirenz, 3TC and d4T. Once-daily NVP with twice
      daily 3TC and d4T is as efficacious as twice-daily NVP, 3TC and d4T. However,
      toxicity may be increased in the once-daily NVP regime. Additional trials of
      sufficient duration are required to provide better evidence for the use of this
      combination as a first line therapy. Ideally, trials should use standardised
      assessment measures especially with respect to measuring viral load, so that
      results can be compared and combined in meta-analyses.

PMID- 16625607
TI  - Aripiprazole for schizophrenia.
AB  - BACKGROUND: Treatment of people with schizophrenia using older typical
      antipsychotic drugs such as haloperidol can be problematic. Many fail to respond
      to these older antipsychotics and more people experience disabling adverse
      effects. Aripiprazole is said to be one of a new generation of atypical
      antipsychotics with good antipsychotic properties and minimal adverse effects.
      OBJECTIVES: To evaluate the effects of aripiprazole for people with schizophrenia
      and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane
      Schizophrenia Group's Register (September 2005) which is based on regular
      searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected
      references of all identified studies for further trials. We contacted relevant
      pharmaceutical companies, the FDA and authors of trials for additional
      information. SELECTION CRITERIA: All clinical randomised trials comparing
      aripiprazole with placebo, typical or atypical antipsychotic drugs for
      schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We
      extracted data independently. For homogenous dichotomous data we calculated
      random effects, relative risk (RR), 95% confidence intervals (CI) and, where
      appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For
      continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS:
      Despite the fact that 7110 people participated in fifteen randomised aripiprazole
      studies, we were unable to extract any usable data on death, service outcomes,
      general functioning, behaviour, engagement with services, satisfaction with
      treatment; economic outcomes or cognitive functioning. Study attrition was very
      large and data reporting poor. Compared with placebo, aripiprazole significantly
      decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.5
      to 0.8, NNT 5 CI 4 to 8). It also produced better compliance with study protocol
      (n=2271, 8 RCTs, RR 0.72 CI 0.5 to 0.97, NNT 26 CI 16 to 239). Aripiprazole may
      decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32
      CI 0.1 to 0.8, NNT 14 CI 11 to 50). Compared with typical antipsychotics there
      were no significant benefits for aripiprazole with regards to global state,
      mental state, quality of life or leaving the study early. Both groups reported
      similar rates of adverse effects, with the exception of akathisia (n= 955 RR 0.31
      CI 0.2 to 0.6, NNT 20 CI 17 to 32) and the need for antiparkinson medication
      (n=1854, 4 RCTs, RR 0.45 CI 0.3 to 0.6, NNT 4 CI 3 to 5) which were lower in
      those receiving aripiprazole. When compared with olanzapine and risperidone,
      aripiprazole was no better or worse on outcomes of global state and leaving the
      study early. The rates of adverse effects were also similar, with the exception
      of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.1, NNT 2 CI 1
      to 2.5) and less prolongation of the average QTc (30 mg/day) (n=200, 1 RCT, WMD 
      10.0, CI -16.99 to -3.0) compared with risperidone. When compared with standard
      care (mixed group receiving typical and atypical antipsychotics) one aripiprazole
      study did have significantly less people not responding to treatment (n=1599, RR
      0.70 CI 0.7 to 0.8, NNT 5 CI 4 to 6 ), not satisfied with care (n=1599, RR 0.62
      CI 0.6 to 0.7, NNT 4 CI 4 to 5) and less people leaving the study early (n=1599,
      1 RCT, RR 0.81 CI 0.7 to 0.9, NNT 13 CI 8 to 39). Results from the five new
      papers identified from the updated review search, did not significantly alter the
      main results or conclusions of the original review. AUTHORS' CONCLUSIONS:
      Aripiprazole may be effective for the treatment of schizophrenia, but it does not
      differ greatly from typical and atypical antipsychotics with respect to treatment
      response, efficacy or tolerability. In comparison with typical antipsychotics,
      aripiprazole may have a lower risk of akathisia, and in comparison to atypical
      antipsychotics, less risk of raised prolactin and prolongation of the QTc
      interval. Clearly reported pragmatic short, medium and long term randomised
      controlled trials should be undertaken to determine its position in everyday
      clinical practice.

PMID- 16625608
TI  - Speed enforcement detection devices for preventing road traffic injuries.
AB  - BACKGROUND: It is estimated that by 2020, road traffic crashes will have moved
      from ninth to third in the world ranking of burden of disease, as measured in
      disability adjusted life years. The identification of effective strategies for
      the prevention of road traffic injuries is of global public health importance.
      Measures aimed at reducing traffic speed are considered essential to preventing
      road injuries; the use of speed enforcement detection devices (including speed
      cameras and radar and laser devices) is one such measure. OBJECTIVES: To assess
      whether the use of speed enforcement detection devices (SEDs) reduces the
      incidence of speeding, road traffic crashes, injuries and deaths. SEARCH
      STRATEGY: We searched the Cochrane Injuries Group's Specialised Register,
      CENTRAL, MEDLINE, EMBASE, Science (and Social Science) Citation Index, TRANSPORT,
      PsycINFO, CINAHL, EconLit. We searched the websites of road safety and motoring
      associations, as well as general internet searches. We handsearched selected
      journals and conference proceedings, and contacted experts in the field. The
      searches were conducted during May to November 2004. SELECTION CRITERIA:
      Randomised controlled trials and controlled before-after studies that assessed
      the impact of speed enforcement detection devices on speeding, road crashes,
      injuries and deaths were eligible for inclusion. For studies involving co
      interventions, SEDs had to be the major intervention focus of the study to be
      eligible. DATA COLLECTION AND ANALYSIS: We independently screened search results,
      assessed studies for inclusion, extracted data and assessed methodological
      quality. Due to variability between and within included studies, a pooled
      analysis was not appropriate. MAIN RESULTS: No randomised controlled trials were
      identified. Twenty-six studies met the inclusion criteria, of which 22 were
      controlled before-after trials incorporating a distinct control or comparison
      group(s) and four were interrupted time series designs with a comparison
      group(s). Fourteen studies reported speed and crash outcomes, seven reported
      crash outcomes only and five reported speed outcomes only. All but one study
      reported an absolute reduction in pre/post average speeds. A pre/post reduction
      in the proportion of speeding vehicles ranged across studies from 5% to 70%
      depending on the speed threshold set. Pre/post reductions of 50% to 65% were
      reported in the proportion of speeding vehicles travelling >15 km/h over the
      speed limit. Compared with controls, the relative improvement was from 1% to 15%
      for average speed and from 14% to 65% for percent speeding. All studies reporting
      crash outcomes reported an absolute pre/post reduction in all crashes and injury
      related crashes. In the vicinity of camera sites these pre/post reductions ranged
      from 14% to 72% for all crashes, 8% to 46% for injury crashes, and 40% to 45% for
      crashes resulting in fatalities or serious injuries. More generalised effects
      over wider areas showed an absolute pre/post crash reduction ranging from 9% to
      35%, 7% to 30% for all injury crashes and 13% to 58% for crashes resulting in
      fatalities alone, or in combination with serious injuries. The studies of longer
      duration showed that these positive trends were either maintained or improved
      with time. Compared with controls, the relative improvement in pre/post crash
      numbers resulting in any type of injury ranged from 5% to 36%. AUTHORS'
      CONCLUSIONS: Despite the methodological limitations of the studies reviewed, the
      consistency of reported positive reductions in speed and crash outcomes across
      all studies suggest that SEDs are a promising intervention for reducing the
      number of road traffic injuries and deaths. More studies of a scientifically
      rigorous nature are necessary to provide a stronger evidence base that these
      interventions are worthwhile. There is a need for international harmonisation of
      data collection methods, including standards on how best to measure speeds and
      collect crash data, over lengthy intervention and follow-up periods, as well as
      some consensus as to the expression of outcomes in studies, so that studies can
      be compared.

PMID- 16625609
TI  - Calcium supplementation for the management of primary hypertension in adults.
AB  - BACKGROUND: Metabolic studies suggest calcium may have a role in the regulation
      of blood pressure. Some epidemiological studies have reported that people with a
      higher intake of calcium tend to have lower blood pressure. Previous systematic
      reviews and meta-analyses have reached conflicting conclusions about whether oral
      calcium supplementation can reduce blood pressure. OBJECTIVES: To evaluate the
      effects of oral calcium supplementation as a treatment for primary hypertension
      in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE,
      Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled
      Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses
      and randomised controlled trials (RCTs) included in the review. SELECTION
      CRITERIA: Inclusion criteria were: 1) RCTs comparing oral calcium supplementation
      with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks;
      3) participants over 18 years old, with raised systolic blood pressure (SBP)
      >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported
      at end of follow-up. We excluded trials where: participants were pregnant;
      received antihypertensive medication which changed during the study; or calcium
      supplementation was combined with other interventions. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently abstracted data and assessed trial quality.
      Disagreements were resolved by discussion or a third reviewer. Random effects
      meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: We included
      13 RCTs (n=485), with between eight and 15 weeks follow-up. The results of the
      individual trials were heterogeneous. Combining all trials, participants
      receiving calcium supplementation as compared to control had a statistically
      significant reduction in SBP (mean difference: -2.5 mmHg, 95% CI: -4.5 to -0.6,
      I(2 )= 42%), but not DBP (mean difference: -0.8 mmHg, 95% CI: -2.1 to 0.4, I(2) =
      48%). Sub-group analyses indicated that heterogeneity between trials could not be
      explained by dose of calcium or baseline blood pressure. Heterogeneity was
      reduced when poor quality trials were excluded. The one trial reporting adequate
      concealment of allocation and the one trial reporting adequate blinding yielded
      results consistent with the primary meta-analysis. AUTHORS' CONCLUSIONS: In view
      of the poor quality of included trials and the heterogeneity between trials, the
      evidence in favour of causal association between calcium supplementation and
      blood pressure reduction is weak and is probably due to bias. This is because
      poor quality studies generally tend to over-estimate the effects of treatment.
      Larger, longer duration and better quality double-blind placebo controlled trials
      are needed to assess the effect of calcium supplementation on blood pressure and
      cardiovascular outcomes.

PMID- 16625610
TI  - Polyclonal and monoclonal antibodies for treating acute rejection episodes in
      kidney transplant recipients.
AB  - BACKGROUND: Registry data shows that between 15-35% kidney recipients will
      undergo treatment for at least one episode of acute rejection within the first
      post transplant year. Treatment options include pulsed steroid therapy, the use
      of an antibody preparation, the alteration of background immunosuppression, or
      combinations of these options. In 2002, in the US, 61.4% patients with an acute
      rejection episode received steroids, 20.4% received an antibody preparation and
      18.2% received both. OBJECTIVES: To determine the benefits and harms of mono- or
      polyclonal antibodies (Ab) used to treat acute rejection in kidney transplant
      recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE
      (1966-June 2005), EMBASE (1980-June 2005), and the specialised register of the
      Cochrane Renal Group (June 2005). SELECTION CRITERIA: Randomised controlled
      trials (RCTs) in all languages comparing all mono- and polyclonal antibody
      preparations, given in combination with any other immunosuppressive agents, for
      the treatment of acute graft rejection, when compared to any other treatment for
      acute rejection. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trials for eligibility and quality, and extracted data. Results are
      expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS:
      Twenty one trials (49 reports, 1387 patients) were identified. Trials were
      generally small, incompletely reported, especially for potential harms, and did
      not define outcome measures adequately. Fourteen trials (965 patients) compared
      therapies for first rejection episodes. Ab was better than steroid in reversing
      rejection (RR 0.57, 95% CI 0.38 to 0.87) and preventing graft loss (death
      censored RR 0.74, CI 0.58 to 0.95) but there was no difference in preventing
      subsequent rejection or death at one year. Seven trials (422 patients)
      investigated Ab treatment of steroid-resistant rejection. There was no benefit of
      muromonab-CD3 over ATG or ALG in either reversing rejection, preventing
      subsequent rejection, preventing graft loss or death. AUTHORS' CONCLUSIONS: In
      reversing first rejection, any antibody is better than steroid and also prevents
      graft loss, but subsequent rejection and patient survival are not significantly
      different. In reversing steroid-resistant rejection the effects of different
      antibodies are also not significantly different. Given the clinical problem
      caused by acute rejection, data are very sparse, and clinically important
      differences in outcomes between widely used interventions have not been excluded.
      Standardised reproducible outcome criteria are needed.

PMID- 16625611
TI  - Patching for corneal abrasion.
AB  - BACKGROUND: Recent audits show that corneal abrasion is a common presenting eye
      complaint. Eye patches are often recommended for treating corneal abrasions
      despite the lack of evidence for their use. This systematic review was conducted
      to determine the effects of the eye patch when used to treat corneal abrasions.
      OBJECTIVES: The objective of this review was to test the hypothesis that patching
      an eye following a corneal abrasion improves healing or provides pain relief.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on
      The Cochrane Library (2005, Issue 2), MEDLINE (1966 to April 2005), EMBASE (1980
      to April 2005), LILACS (13 April 2005), NRR (2005, Issue 2) and SIGLE (December
      2004). There were no language or date restrictions in the searches. We also
      searched the reference lists of included studies, unpublished 'grey' literature
      and conference proceedings and contacted pharmaceutical companies for details of
      unpublished trials. SELECTION CRITERIA: We included randomised and quasi
      randomised controlled trials that compared patching the eye with no patching to
      treat simple corneal abrasions. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted
      investigators for further information regarding quality of trials. The primary
      outcome was healing of the corneal epithelium and secondary outcomes were related
      to pain. MAIN RESULTS: Eleven trials, which randomised a total of 1014
      participants, were included in the review. Meta-analysis of seven studies with
      dichotomous healing outcomes favoured no patching on the first day of healing
      (risk ratio (RR) 0.89, 95% Confidence Interval (CI) 0.79 to 0.99). For days two
      and three there was no significant difference between the two groups. Of the nine
      trials that measured pain scores two favoured no patching and none favoured
      patching. Complication rates were low and no differences were noted in these
      between the two groups. No-patch groups generally received more adjuvant
      treatment with antibiotics and/or cycloplegics than the patch group which is an
      important confounding factor. AUTHORS' CONCLUSIONS: Treating simple corneal
      abrasions with a patch does not improve healing rates on the first day post
      injury and does not reduce pain. In addition, use of patches results in a loss of
      binocular vision. Therefore it is recommended that patches should not be used for
      simple corneal abrasions. Further research should focus on large (greater than 10
      mm(2)) abrasions.

PMID- 16625612
TI  - Interventions for cutaneous molluscum contagiosum.
AB  - BACKGROUND: Molluscum contagiosum is a common skin infection, caused by a virus,
      which will usually resolve within months in people with a normal immune system.
      Many treatments have been promoted for molluscum contagiosum but a clear evidence
      base supporting them is lacking. OBJECTIVES: To assess the effects of management
      strategies (including waiting for natural resolution) for cutaneous, non-genital
      molluscum contagiosum in healthy people. SEARCH STRATEGY: We searched the Skin
      Group Specialised Register (March 2004), the Cochrane Central Register of
      Controlled Trials (2004, Issue 2), MEDLINE (from 1966 to March 2004), EMBASE
      (from 1980 to March 2004) and LILACS (from 1982 to March 2004) databases. We also
      searched reference lists and contacted pharmaceutical companies and experts in
      the field. SELECTION CRITERIA: Randomised controlled trials for treatment of
      molluscum contagiosum were investigated. Trials on sexually transmitted molluscum
      contagiosum and in people with lowered immunity (including those with HIV
      infection) were excluded. DATA COLLECTION AND ANALYSIS: Study selection and
      assessment of methodological quality were carried out by two independent authors.
      As similar comparisons between two interventions were not made in more than one
      study, statistical pooling was not performed. MAIN RESULTS: Five studies, with a
      total number of 137 participants, examined the effects of topical (three
      studies), systemic and homoeopathic interventions (one study each). Limited
      evidence was found for sodium nitrite co-applied with salicylic acid compared to
      salicylic acid alone (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.23 to
      9.92). No statistically significant differences were found for topical povidone
      iodine plus salicylic acid compared to povidone iodine alone (RR of cure 1.67,
      95% CI 0.81 to 3.41) or compared to salicylic acid alone. Also no statistically
      significant differences were found for potassium hydroxide compared to placebo;
      systemic treatment with cimetidine versus placebo or systemic treatment with
      calcarea carbonica, a homoeopathic drug, versus placebo (RR 5.57, 95% CI 0.93 to
      33.54). Study limitations included no blinding (two studies), many dropouts
      (three studies) and no intention-to-treat analysis (two studies); small study
      sizes may have led to important differences being missed. None of the evaluated
      treatment options were associated with serious adverse effects. AUTHORS'
      CONCLUSIONS: No single intervention has been shown to be convincingly effective
      in treating molluscum contagiosum.

PMID- 16625613
TI  - Hepatitis B immunisation for newborn infants of hepatitis B surface antigen
      positive mothers.
AB  - BACKGROUND: Hepatitis B vaccine and hepatitis B immunoglobulin are considered for
      newborn infants of HBsAg-positive mothers to prevent hepatitis B infection.
      OBJECTIVES: To assess the beneficial and harmful effects of hepatitis B vaccines
      and hepatitis B immunoglobulin in newborn infants of HBsAg-positive mothers.
      SEARCH STRATEGY: Trials were identified through The Cochrane Neonatal Group
      Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials
      Register, The Cochrane Central Register of Controlled Trials in The Cochrane
      Library, MEDLINE, and EMBASE (until February 2004), authors of trials, and
      pharmaceutical companies. SELECTION CRITERIA: Randomised clinical trials
      comparing: plasma-derived vaccine (PDV) or recombinant vaccine (RV) versus no
      intervention, placebo, or other active vaccines; hepatitis B immunoglobulin
      versus no intervention, placebo, or other control immunoglobulin; as well as PDV
      or RV plus hepatitis B immunoglobulin versus no intervention, placebo, or other
      control vaccines or immunoglobulin. DATA COLLECTION AND ANALYSIS: Outcomes are
      assessed at maximal follow-up. The primary outcome measure was hepatitis B
      occurrence, based on a blood specimen positive for HBsAg, HBeAg, or antibody to
      hepatitis B core antigen (anti-HBc). Binary outcomes are reported as relative
      risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed
      with regard to methodological quality of the trial, mother's HBe-Ag status, and
      time of immunisation after birth. MAIN RESULTS: We identified 29 randomised
      clinical trials, five of which were considered high quality. Only three trials
      reported inclusion of hepatitis B e-antigen negative mothers. Compared with
      placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95%
      confidence interval (CI) 0.20 to 0.40, 4 trials). No significant differences of
      hepatitis B occurrence were found comparing recombinant vaccine (RV) versus
      plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high
      dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR
      0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no intervention,
      hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B
      immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR
      0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08,
      95% CI 0.03 to 0.17, 3 trials). Compared with vaccine, vaccine plus hepatitis B
      immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10
      trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few
      trials reported on adverse events. AUTHORS' CONCLUSIONS: Vaccine, hepatitis B
      immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B
      occurrence in newborn infants of HBsAg positive mothers.

PMID- 16625614
TI  - Music for pain relief.
AB  - BACKGROUND: The efficacy of music for the treatment of pain has not been
      established. OBJECTIVES: To evaluate the effect of music on acute, chronic or
      cancer pain intensity, pain relief, and analgesic requirements. SEARCH STRATEGY:
      We searched The Cochrane Library, MEDLINE, EMBASE, PsycINFO, LILACS and the
      references in retrieved manuscripts. There was no language restriction. SELECTION
      CRITERIA: We included randomized controlled trials that evaluated the effect of
      music on any type of pain in children or adults. We excluded trials that reported
      results of concurrent non-pharmacological therapies. DATA COLLECTION AND
      ANALYSIS: Data was extracted by two independent review authors. We calculated the
      mean difference in pain intensity levels, percentage of patients with at least
      50% pain relief, and opioid requirements. We converted opioid consumption to
      morphine equivalents. To explore heterogeneity, studies that evaluated adults,
      children, acute, chronic, malignant, labor, procedural, or experimental pain were
      evaluated separately, as well as those studies in which patients chose the type
      of music. MAIN RESULTS: Fifty-one studies involving 1867 subjects exposed to
      music and 1796 controls met inclusion criteria. In the 31 studies evaluating mean
      pain intensity there was a considerable variation in the effect of music,
      indicating statistical heterogeneity ( I(2) = 85.3%). After grouping the studies
      according to the pain model, this heterogeneity remained, with the exception of
      the studies that evaluated acute postoperative pain. In this last group, patients
      exposed to music had pain intensity that was 0.5 units lower on a zero to ten
      scale than unexposed subjects (95% CI: -0.9 to -0.2). Studies that permitted
      patients to select the music did not reveal a benefit from music; the decline in
      pain intensity was 0.2 units, 95% CI (-0.7 to 0.2). Four studies reported the
      proportion of subjects with at least 50% pain relief; subjects exposed to music
      had a 70% higher likelihood of having pain relief than unexposed subjects (95%
      CI: 1.21 to 2.37). NNT = 5 (95% CI: 4 to 13). Three studies evaluated opioid
      requirements two hours after surgery: subjects exposed to music required 1.0 mg
      (18.4%) less morphine (95% CI: -2.0 to -0.2) than unexposed subjects. Five
      studies assessed requirements 24 hours after surgery: the music group required
      5.7 mg (15.4%) less morphine than the unexposed group (95% CI: -8.8 to -2.6).
      Five studies evaluated requirements during painful procedures: the difference in
      requirements showed a trend towards favoring the music group (-0.7 mg, 95% CI: 
      1.8 to 0.4). AUTHORS' CONCLUSIONS: Listening to music reduces pain intensity
      levels and opioid requirements, but the magnitude of these benefits is small and,
      therefore, its clinical importance unclear.

PMID- 16625615
TI  - Prophylactic antibiotics for manual removal of retained placenta in vaginal
      birth.
AB  - BACKGROUND: Retained placenta is a potentially life-threatening condition because
      of its association with postpartum haemorrhage. Manual removal of placenta
      increases the likelihood of bacterial contamination in the uterine cavity.
      OBJECTIVES: To compare the effectiveness and side-effects of routine antibiotic
      use for manual removal of placenta in vaginal birth in women who received
      antibiotic prophylaxis and those who did not and to identify the appropriate
      regimen of antibiotic prophylaxis for this procedure. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 November
      2005), CENTRAL (The Cochrane Library, Issue 4, 2005), MEDLINE (from 1966 to
      January 2005), EMBASE (from 1980 to January 2005), CINAHL (from 1982 to January
      2005) and LILACS (from 1982 to January 2005). SELECTION CRITERIA: All randomized
      controlled trials comparing antibiotic prophylaxis and placebo or non antibiotic
      use to prevent endometritis after manual removal of placenta in vaginal birth.
      DATA COLLECTION AND ANALYSIS: If eligible trials were to be identified, trial
      quality would be assessed and data would be extracted, unblinded by two review
      authors independently. MAIN RESULTS: No studies that met the inclusion criteria
      were identified. AUTHORS' CONCLUSIONS: There are no randomized controlled trials
      to evaluate the effectiveness of antibiotic prophylaxis to prevent endometritis
      after manual removal of placenta in vaginal birth.

PMID- 16625616
TI  - Aqueous shunts for glaucoma.
AB  - BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in
      primary and secondary glaucomas that fail medical, laser, and other surgical
      therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and
      safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in
      January 2006, LILACS to February 2004 and reference lists of included trials.
      SELECTION CRITERIA: We included all randomized and quasi-randomized trials in
      which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data for included studies and a third adjudicated
      discrepancies. We contacted investigators for missing information. We used fixed
      effect models and summarized continuous outcomes using mean differences. MAIN
      RESULTS: We included fifteen trials with a total of 1153 participants with mixed
      diagnoses. Five studies reported details sufficient to verify the method of
      randomization but only two had adequate allocation concealment. Data collection
      and follow-up times were variable.Meta-analysis of two trials comparing Ahmed
      implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11
      to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta
      analysis of two trials comparing double-plate Molteno implant with the Schocket
      shunt was not done due to substantial heterogeneity. One study comparing ridged
      with standard double-plate Molteno implants found no clinically significant
      differences in outcome. Two trials investigating the effectiveness of adjunctive
      mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit
      with MMC. Two trials that investigated surgical technique variations with the
      Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule.
      One study concluded there were outcome advantages with a double versus a single
      plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2)
      Baerveldt shunts found no clinically significant advantage of the larger device
      but neither of these trials included all patients randomized. One study suggested
      improved clinical outcome when MMC was employed with a newly described shunt
      including ultrasound supporting the conclusion. One small study did not
      demonstrate an outcome advantage to systemic steroid use postoperatively with
      single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP)
      with Ahmed implant in complicated glaucomas found no evidence of better IOP
      control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few
      randomized trials have been published on aqueous shunts and methodology and data
      quality among them is poor. To date there is no evidence of superiority of one
      shunt over another.

PMID- 16625617
TI  - Drugs for treating paracoccidioidomycosis.
AB  - BACKGROUND: Paracoccidioidomycosis is a fungal infection found in particular
      geographic localities in Latin America. Treatment can last for up to two years is
      often associated with complications, including relapse, but people may die
      without it. OBJECTIVES: To evaluate drugs used for treating
      paracoccidioidomycosis. SEARCH STRATEGY: We searched the Cochrane Infectious
      Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library
      2005, Issue 4), PubMed (1966 to January 2006), EMBASE (1974 to January 2006),
      LILACS (1982 to January 2006), conference proceedings, and reference lists. We
      also contacted researchers and pharmaceutical companies. SELECTION CRITERIA:
      Randomized controlled trials comparing drugs for treating people with
      paracoccidioidomycosis. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial eligibility and methodological quality, and extracted data,
      including adverse events. MAIN RESULTS: One trial with 42 participants met the
      inclusion criteria that compared imidazoles (itraconazole and ketoconazole) with
      sulfadiazine. No difference was detected for cure or clinical improvement, or
      serological titres after 10 months of treatment, and there was no difference
      detected in adverse events. AUTHORS' CONCLUSIONS: The small number of
      participants and the short follow-up period impede definitive conclusions.

PMID- 16625618
TI  - Oral antibiotics versus parenteral antibiotics for severe pneumonia in children.
AB  - BACKGROUND: Acute respiratory infection (ARI) is one of the leading causes of
      morbidity and mortality in children under five years of age in developing
      countries. When hospitalisation is required, the usual practice includes
      administering parenteral antibiotics if a bacterial infection is suspected. This
      has disadvantages as it causes pain and discomfort to the children, which may
      lead to treatment refusal or reduced compliance. It is also associated with
      needle-related complications. In some settings this equipment is in short supply
      or unavailable necessitating transfer of the child, which increases risks and
      healthcare costs. OBJECTIVES: To determine the equivalence in effectiveness and
      safety of oral antibiotic compared to parenteral antibiotic therapies in the
      treatment of severe pneumonia in children between three months and five years of
      age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 2, 2005); MEDLINE (January 1966 to
      July 2005); EMBASE (January 1990 to July 2005) and LILACS (February 2005).
      SELECTION CRITERIA: The review included published or unpublished randomised
      controlled trials (RCTs) and quasi-RCTs comparing any oral antibiotic therapy
      with any parenteral antibiotic therapy for the treatment of severe pneumonia in
      children from three months to five years of age. DATA COLLECTION AND ANALYSIS:
      The search yielded more than 1300 titles. Only three studies met all criteria for
      eligibility. One of the identified trials is yet to publish its results. We did
      not perform a meta-analysis because of clinical heterogeneity of therapies
      compared in the included trials. MAIN RESULTS: Campbell 1988 compared oral co
      trimoxazole versus intramuscular procaine penicillin followed by oral ampicillin
      in 134 children. At the seventh day of follow up, treatment failure occurred in
      6/66 (9.1%) in the oral co-trimoxazole group and 7/68 (10.2%) in the combined
      treatment group. The risk difference was -0.01% (95% confidence interval (CI) 
      0.11 to 0.09). The APPIS Group 2004 evaluated 1702 patients comparing oral
      amoxicillin versus intravenous penicillin for two days followed by oral
      amoxicillin. After 48 hours, treatment failure occurred in 161/845 (19%) in the
      amoxicillin group and 167/857 (19%) in the parenteral penicillin group. The risk
      difference was -0.4% (95% CI -4.2 to 3.3). The authors reported similar recovery
      in both groups at 5 and 14 days. AUTHORS' CONCLUSIONS: Oral therapy appears to be
      an effective and safe alternative to parenteral antibiotics in hospitalised
      children with severe pneumonia who do not have any serious signs or symptoms.

PMID- 16625619
TI  - Preoperative bathing or showering with skin antiseptics to prevent surgical site
      infection.
AB  - BACKGROUND: Surgical site infections (SSIs) are wound infections that occur after
      invasive (surgical) procedures. Preoperative bathing or showering with an
      antiseptic skin wash product is a well-accepted procedure for reducing skin
      bacteria (microflora). It is less clear whether reducing skin microflora leads to
      a lower incidence of surgical site infection. OBJECTIVES: To review the evidence
      for preoperative bathing or showering with antiseptics for the prevention of
      hospital-acquired (nosocomial) surgical site infection. SEARCH STRATEGY: We
      searched the Cochrane Wounds Group Specialised Register (December 2005), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,
      2005), MEDLINE (January 1966 to December 2005) and reference lists of articles.
      SELECTION CRITERIA: Randomised controlled trials comparing any antiseptic
      preparation used for preoperative full-body bathing or showering with non
      antiseptic preparations in patients undergoing surgery. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed studies for selection, trial quality
      and extracted data. Study authors were contacted for additional information. MAIN
      RESULTS: Six trials involving a total of 10,007 participants were included. Three
      of the included trials had three comparison groups. The antiseptic used in all
      trials was 4% chlorhexidine gluconate (Hibiscrub). Three trials involving 7691
      participants compared chlorhexidine with a placebo. Bathing with chlorhexidine
      compared with a placebo did not result in a statistically significant reduction
      in SSIs; the relative risk of SSI (RR) was 0.91 (95% confidence interval (CI)
      0.80 to 1.04). When only trials of high quality were included in this comparison,
      the RR of SSI was 0.95 (95%CI 0.82 to 0.10). Three trials of 1443 participants
      compared bar soap with chlorhexidine; when combined there was no difference in
      the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Two trials of 1092 patients
      compared bathing with chlorhexidine with no washing. No difference was found in
      the postoperative SSI rate between patients who washed with chlorhexidine and
      those who did not wash preoperatively (RR 0.70, 95% CI 0.19 to 2.58). AUTHORS'
      CONCLUSIONS: This review provides evidence of no benefit for preoperative
      showering or bathing with chlorhexidine over other wash products, to reduce
      surgical site infection. Efforts to reduce the incidence of nosocomial surgical
      site infection should focus on interventions where effect has been demonstrated.

PMID- 16625620
TI  - Total versus subtotal hysterectomy for benign gynaecological conditions.
AB  - BACKGROUND: Hysterectomy using an abdominal approach removes either the uterus
      alone (subtotal hysterectomy) or both the uterus and the cervix (total
      hysterectomy). The latter is more common but outcomes have not been
      systematically compared. OBJECTIVES: To assess and compare outcomes with subtotal
      hysterectomy versus total abdominal hysterectomy for benign gynaecological
      conditions. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and
      Subfertility Group's specialised register of controlled trials (December 2005),
      Central (December 2005), Medline (1966 to December 2005), EmBase (1980 to
      December 2005), Biological Abstracts (1980 to December 2005), the National
      Research Register and relevant citation lists. SELECTION CRITERIA: Only
      randomised controlled trials of women undergoing either total or subtotal
      hysterectomy for benign gynaecological conditions were included. DATA COLLECTION
      AND ANALYSIS: Three trials that included 733 participants were included.
      Independent selection of trials and data extraction were undertaken by 2
      reviewers and results compared. MAIN RESULTS: There was no evidence of a
      difference in the rates of incontinence, constipation or measures of sexual
      function. In one unblinded trial, a significantly greater proportion of women
      indicated that they had frequent episodes of urinary incontinence after subtotal
      hysterectomy when compared with total hysterectomy (OR=2.1, 1.02 to 4.3), but
      these results were not confirmed by the other two trials that measured both
      stress and urge incontinence and urinary frequency. . Length of surgery and
      amount of blood lost during surgery were significantly reduced during subtotal
      hysterectomy when compared with total hysterectomy, but there was no evidence of
      a difference in the odds of transfusion. Febrile morbidity was less likely
      (OR=0.43, 0.25 to 0.75) and ongoing cyclical vaginal bleeding one year after
      surgery was more likely (OR=11.3, 4.1 to 31.2) after subtotal when compared with
      total hysterectomy. There was no evidence of a difference in the rates of other
      complications, recovery from surgery or readmission rates. AUTHORS' CONCLUSIONS:
      This review has not confirmed the perception that subtotal hysterectomy offers
      improved outcomes for sexual, urinary or bowel function when compared with total
      abdominal hysterectomy. Surgery is shorter and intraoperative blood loss and
      fever are reduced but women are more likely to experience ongoing cyclical
      bleeding up to a year after surgery with subtotal hysterectomy compared to total
      hysterectomy.

PMID- 16625621
TI  - Rapid versus slow withdrawal of antiepileptic drugs.
AB  - BACKGROUND: The ideal objective of treating a person with epilepsy is to induce
      remission by usage of antiepileptic drugs (AEDs) and withdraw the AEDs without
      causing seizure recurrence. Prolonged usage of AEDs may have long-term side
      effects. Hence when a person with epilepsy is in remission (free of seizures for
      some time) it is logical to attempt to discontinue the medication. The timing of
      withdrawal and the mode of withdrawal arise while contemplating withdrawal of
      AEDs. This review proposes to examine the evidence for the rate of withdrawal of
      AEDs (whether rapid or slow tapering) and its effect on recurrence of seizure.
      This review also examines the effect of variables such as age of seizure onset,
      seizure types, presence of neurological deficits, mental subnormality, aetiology
      of epilepsy, type of AED, EEG findings or duration of seizure freedom on the risk
      of recurrence of seizures with the two tapering regimens. OBJECTIVES: (1) To
      quantify risk of seizure recurrence after rapid (taper period of three months or
      less) or slow (taper period or more than three months) discontinuation of
      antiepileptic drugs in adults with epilepsy who are in remission. (2) To quantify
      the risk of seizure recurrence after rapid (taper period of three months or less)
      or slow (taper period of more than three months) discontinuation of antiepileptic
      drugs in children with epilepsy who are in remission. (3) To attempt to assess
      which variables modify the risk of seizure recurrence. SEARCH STRATEGY: We
      searched the Cochrane Epilepsy Group's Specialized Register (August 2005), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      Issue 3, 2005), MEDLINE (1966 to September 2004) and cross-references from
      identified studies. No language restrictions were imposed. SELECTION CRITERIA:
      Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow
      manner after varying periods of seizure control in patients with epilepsy. DATA
      COLLECTION AND ANALYSIS: Both review authors independently assessed the trials
      for inclusion and extracted the data. The outcomes assessed included seizure
      relapse (i.e. the percentage of patients experiencing seizure recurrence after
      withdrawal of AED); time to recurrence of seizure following withdrawal;
      occurrence of status epilepticus; mortality; morbidity due to seizure such as
      injuries, fractures, aspiration pneumonia; and quality of life (if assessed by
      validated scale). MAIN RESULTS: One trial with weak methodology involving 149
      children was included with a mean age of seizure onset of four years, mean age of
      11 years at the time of starting the taper. The rapid taper group (six weeks)
      recruited 81 participants and the slow taper group (nine months) included 68
      participants, out of whom 11 and 5 were lost to follow up even before the taper
      began respectively. The number of participants who were seizure free in the rapid
      and slow taper groups were 40 and 44 respectively at the end of one year follow
      up (OR 0.53, 95% CI 0.27 to 1.03); 30 and 29 respectively at the end of two
      years, (OR 0.79, 95% CI 0.41 to 1.53); 24 and 14 respectively at the end of three
      years (OR 1.62, 95% CI 0.76 to 3.46); 18 and 8 respectively at the end of four
      years (OR 2.14, 95% CI 0.87 to 5.3); 10 and 6 respectively at the end of five
      years (OR 1.46, 95% CI 0.5 to 4.23). AUTHORS' CONCLUSIONS: In view of
      methodological deficiencies and small sample size, in the solitary study
      identified, we cannot derive any reliable conclusions regarding the optimal rate
      of tapering of AEDs. Further studies are needed in adults as well as in children
      to investigate the rate of withdrawal of AEDs and to study the effects of
      variables such as seizure types, its aetiology, mental retardation, EEG
      abnormalities, presence of neurological deficits and other co-morbidities on the
      rate of tapering.

PMID- 16625622
TI  - Acupuncture for epilepsy.
AB  - BACKGROUND: Seizures are poorly controlled in many people with epilepsy despite
      adequate current antiepileptic treatments. There is increasing interest in
      alternative therapies such as acupuncture; however, it remains unclear whether
      the existing evidence is rigorous enough to support the use of acupuncture.
      OBJECTIVES: To determine the effectiveness and safety of acupuncture in people
      with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's
      Specialized Register (June 2005) and the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 3, 2005). We also searched MEDLINE,
      EMBASE, CINAHL, AMED, TCMLARS, China Biological Medicine Database, Chinese
      Acupuncture Trials Register, National Center for Complementary and Alternative
      Medicine, and National Institute of Health Clinical Trials Database from
      inception to June 2005. Reference lists from relevant trials were reviewed. No
      language restrictions were imposed. SELECTION CRITERIA: Randomised controlled
      trials evaluating any form of acupuncture involving people of any age with any
      type of epilepsy were included. Trials included were those comparing acupuncture
      with placebo, sham or no treatment; or comparing acupuncture plus other
      treatments with the same other treatments. Trials that only compared different
      acupuncture methods or compared acupuncture alone with other treatments were
      excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted trial data and assessed trial quality using the Jadad score. Relative
      risk (RR) was used for binary data and weighted mean difference for continuous
      data, and 95% confidence intervals are given. Where possible, analyses were by
      intention to treat. MAIN RESULTS: Three small trials of varying methodological
      quality and with short follow up met the inclusion criteria. Two studied children
      in China and one studied adults in Norway. The two Chinese studies compared
      acupuncture plus Chinese herbs with Chinese herbs alone while the Norwegian study
      compared acupuncture with sham acupuncture. The two Chinese studies found that
      more children treated with acupuncture achieved 75% or greater reduction in
      seizure frequency (RR 1.52, 95% CI 1.12 to 2.05) and seizure duration (RR 2.38,
      95% CI 1.13 to 5) with a significant 50% or greater reduction in seizure duration
      (RR 1.36, 95% CI 1.07 to 1.73). However, the two trials were of low quality
      without adequate description of randomisation method, concealment of
      randomisation or blinding. On the other hand, the higher quality Norwegian trial
      found that acupuncture did not improve the mean seizure frequency, seizure-free
      weeks, or quality of life in adults. AUTHORS' CONCLUSIONS: The current evidence
      does not support acupuncture as a treatment for epilepsy. Much larger high
      quality clinical trials employing appropriate controls are needed.

PMID- 16625623
TI  - Medical and surgical treatment for ocular myasthenia.
AB  - BACKGROUND: Approximately 50% of people with myasthenia gravis present initially
      with purely ocular symptoms, so called ocular myasthenia and between 50 to 60% of
      these people will progress to develop generalized disease. The vast majority will
      do so within the first one to two years. There is controversy surrounding the
      appropriate management of patients with ocular myasthenia. OBJECTIVES: To perform
      a systematic review of the literature relevant to the treatment of ocular
      myasthenia and to answer three specific questions. Are there any medical or
      surgical treatments that have an impact on the risk of progression from ocular to
      generalized myasthenia gravis? Are there any medical or surgical treatments that
      improve symptoms of diplopia or ptosis in ocular myasthenia? What is the
      frequency of side effects associated with treatments used in people with ocular
      myasthenia? SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      Trials Register (searched December 2004), MEDLINE (1996 to 2004) and EMBASE (1980
      to 2004) for randomized controlled trials as well as case-control and cohort
      studies. The titles and abstracts of all articles were read by both authors and
      the full text of all articles that were of possible relevance was reviewed in
      full. The references of all manuscripts included in the review were scanned to
      identify additional articles of relevance and experts in the field were contacted
      to identify additional published and unpublished data. Where necessary and
      possible, we contacted authors for further information. SELECTION CRITERIA: To be
      included in the review, studies had to meet three criteria: (a) randomized (or
      quasi-randomized) controlled study design; (b) active treatment compared to
      placebo, no treatment or some other treatment; and (c) results reported
      separately for patients with ocular myasthenia (grade 1) as defined by the
      Myasthenia Gravis Foundation of America. DATA COLLECTION AND ANALYSIS: We
      collected data regarding the risk of progression to generalized myasthenia
      gravis, improvement in ocular symptoms, and the frequency of treatment-related
      side effects. MAIN RESULTS: We identified two randomized controlled trials
      relevant to the treatment of ocular myasthenia, only one of which reported
      results in terms of the pre-specified outcome measures used in this review. This
      study included only three participants and was of limited methodological quality.
      In the absence of data from randomized controlled trials, we present a review of
      the available observational data. AUTHORS' CONCLUSIONS: There are no data from
      randomized controlled trials on the impact of any form of treatment on the risk
      of progression from ocular to generalized myasthenia gravis. The available
      randomized controlled literature does not permit any meaningful conclusions about
      the efficacy of any form of treatment for ocular myasthenia. Data from several
      reasonably good quality observational studies suggest that corticosteroids and
      azathioprine may be beneficial in reducing the risk of progression to generalized
      myasthenia gravis.

PMID- 16625624
TI  - Calcium supplementation for improving bone mineral density in children.
AB  - BACKGROUND: Clinical trials have shown that calcium supplementation in children
      can increase bone mineral density (BMD) although this effect may not be
      maintained. There has been no quantitative systematic review of this
      intervention. OBJECTIVES: . To determine the effectiveness of calcium
      supplementation for improving BMD in children. . To determine if any effect
      varies by sex, pubertal stage, ethnicity or level of physical activity, and if
      any effect persists after supplementation is ceased. SEARCH STRATEGY: We searched
      CENTRAL, (Cochrane Central Register of Controlled Trials) (Issue 3, 2005),
      MEDLINE (1966 to 1 April 2005), EMBASE (1980 to 1 April 2005), CINAHL (1982 to 1
      April 2005), AMED (1985 to 1 April 2005), MANTIS (1880 to 1 April 2005) ISI Web
      of Science (1945 to 1 April 2005), Food Science and Technology Abstracts (1969 to
      1 April 2005) and Human Nutrition (1982 to 1 April 2005). Conference abstract
      books (Osteoporosis International, Journal of Bone and Mineral Research) were
      hand-searched. SELECTION CRITERIA: Randomised controlled trials of calcium
      supplementation (including by food sources) compared with placebo, with a
      treatment period of at least 3 months in children without co-existent medical
      conditions affecting bone metabolism. Outcomes had to include areal or volumetric
      BMD, bone mineral content (BMC), or in the case of studies using quantitative
      ultrasound, broadband ultrasound attenuation and ultrasonic speed of sound,
      measured after at least 6 months of follow-up. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality and extracted data including adverse
      events. We contacted study authors for additional information. MAIN RESULTS: The
      19 trials included 2859 participants, of which 1367 were randomised to
      supplementation and 1426 to placebo. There was no heterogeneity in the results of
      the main effects analyses to suggest that the studies were not comparable. There
      was no effect of calcium supplementation on femoral neck or lumbar spine BMD.
      There was a small effect on total body BMC (standardised mean difference (SMD)
      +0.14, 95% CI+0.01, +0.27) and upper limb BMD (SMD +0.14, 95%CI +0.04, +0.24).
      Only the effect in the upper limb persisted after supplementation ceased
      (SMD+0.14, 95%CI+0.01, +0.28). This effect is approximately equivalent to a 1.7%
      greater increase in supplemented groups, which at best would reduce absolute
      fracture risk in children by 0.1-0.2%per annum. There was no evidence of effect
      modification by baseline calcium intake, sex, ethnicity, physical activity or
      pubertal stage. Adverse events were reported infrequently and were minor.
      AUTHORS' CONCLUSIONS: While there is a small effect of calcium supplementation in
      the upper limb, the increase in BMD which results is unlikely to result in a
      clinically significant decrease in fracture risk. The results do not support the
      use of calcium supplementation in healthy children as a public health
      intervention. These results cannot be extrapolated to children with medical
      conditions affecting bone metabolism.

PMID- 16625625
TI  - Chinese herbal medicine for the treatment of pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia is a common disorder of pregnancy with uncertain
      etiology. In Chinese herbal medicines, a number of herbs are used for treating
      pre-eclampsia. Traditional Chinese medicine considers that, when a woman is
      pregnant, most of the blood of the mother is directed to the placenta to provide
      the baby with the required nutrition; other maternal organs may in consequence be
      vulnerable to damage. These organs include the liver, the spleen, and the
      kidneys. The general effects of Chinese herbal medicines that can protect these
      organs may be valuable in pre-eclampsia by encouraging vasodilatation, increasing
      blood flow, and decreasing platelet aggregation. The use of Chinese herbal
      medicine is often based on the individual and presence of traditional Chinese
      medicine symptoms. OBJECTIVES: To assess the effect of Chinese herbal medicine
      for treating pre-eclampsia and compare it with that of placebo, no treatment or
      Western medicine. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Groups Trial Register (31 March 2005), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library, Issue 1, 2005), MEDLINE (1969 to
      December 2004), EMBASE (1984 to March 2004) and CBM (1978 to February 2005) and
      we handsearched several main journals published in China. SELECTION CRITERIA:
      Randomized controlled trials in which Chinese herbal medicine was used for
      treating pre-eclampsia. DATA COLLECTION AND ANALYSIS: One review author assessed
      trials for inclusion. The trials were also assessed by a second review author if
      there was any doubt about whether or not to include the trial. Analysis was not
      performed as there were no trials included in this review. MAIN RESULTS: No
      trials were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: The
      effect of Chinese herbal medicine for treating pre-eclampsia remains unclear.
      There are currently no randomized controlled trials to address the efficacy and
      safety of Chinese herbal medicine for the treatment of pre-eclampsia. Well
      conducted randomized controlled trials are required.

PMID- 16625626
TI  - Photorefractive keratectomy (PRK) versus laser-assisted in-situ keratomileusis
      (LASIK) for myopia.
AB  - BACKGROUND: Myopia (also known as short-sightedness or near-sightedness) is an
      ocular condition in which the refractive power of the eye is greater than is
      required, resulting in light from distant objects being focused in front of the
      retina instead of directly on it. The two most commonly used surgical techniques
      to permanently correct myopia are photorefractive keratectomy (PRK) and laser
      assisted in-situ keratomileusis (LASIK). OBJECTIVES: The aim of this review was
      to compare the effectiveness and safety of PRK and LASIK for correction of
      myopia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) in The Cochrane Library (2005, Issue 3), MEDLINE (1966 to
      September 2005), EMBASE (1980 to September 2005) and LILACs (1982 to 3 November
      2005). We also searched the reference lists of the studies and the Science
      Citation Index. SELECTION CRITERIA: We included randomised controlled trials
      comparing PRK and LASIK for correction of any degree of myopia. We also included
      data on adverse events from prospective multicentre consecutive case series in
      the Food and Drugs Administration (FDA) trials database
      (http//www.fda.gov/cdrh/LASIK/lasers.htm). DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality and extracted data. Data were
      summarised using odds ratio and mean difference. Odds ratios were combined using
      a random-effects model after testing for heterogeneity. MAIN RESULTS: This review
      included six randomised controlled trials involving a total of 417 eyes, of which
      201 were treated with PRK and 216 with LASIK. We found that although LASIK gives
      a faster visual recovery than PRK, the effectiveness of these two procedures is
      comparable. We found some evidence that LASIK may be less likely than PRK to
      result in loss of best spectacle-corrected visual acuity. AUTHORS' CONCLUSIONS:
      LASIK gives a faster visual recovery than PRK but the effectiveness of these two
      procedures is comparable. Further trials using contemporary techniques are
      required to determine whether LASIK and PRK are equally safe.

PMID- 16625627
TI  - Interventions used to improve control of blood pressure in patients with
      hypertension.
AB  - BACKGROUND: It is well recognized that patients with high blood pressure
      (hypertension) in the community frequently fail to meet treatment goals - a
      condition labeled as "uncontrolled" hypertension. The optimal way in which to
      organize and deliver care to patients who have hypertension so that they reach
      treatment goals has not been clearly identified. OBJECTIVES: To determine the
      effectiveness of interventions to improve control of blood pressure in patients
      with hypertension. To evaluate the effectiveness of reminders on improving the
      follow-up of patients with hypertension. SEARCH STRATEGY: All-language search of
      all articles (any year) in the Cochrane Controlled Trials Register (CCTR),
      Medline and Embase from June 2000. SELECTION CRITERIA: Randomized controlled
      trials (RCTs) of patients with hypertension that evaluated the following
      interventions: (1) self-monitoring (2) educational interventions directed to the
      patient (3) educational interventions directed to the health professional (4)
      health professional (nurse or pharmacist) led care (5) organisational
      interventions that aimed to improve the delivery of care (6) appointment reminder
      systems. Outcomes assessed were: (1) mean systolic and diastolic blood pressure(
      2) control of blood pressure (3) proportion of patients followed up at clinic.
      DATA COLLECTION AND ANALYSIS: Two authors extracted data independently and in
      duplicate and assessed each study according to the criteria outlined by the
      Cochrane Collaboration Handbook. MAIN RESULTS: 56 RCTs met our inclusion
      criteria. The methodological quality of included studies was variable. An
      organized system of regular review allied to vigorous antihypertensive drug
      therapy was shown to reduce blood pressure (weighted mean difference -8.2/-4.2
      mmHg, -11.7/-6.5 mmHg, -10.6/-7.6 mmHg for 3 strata of entry blood pressure) and
      all-cause mortality at five years follow-up (6.4% versus 7.8%, difference 1.4%)
      in a single large RCT- the Hypertension Detection and Follow-Up study. Other
      interventions had variable effects. Self-monitoring was associated with moderate
      net reduction in diastolic blood pressure (weighted mean difference (WMD): -2.0
      mmHg, 95%CI: -2.7 to -1.4 mmHg, respectively. Appointment reminders increased the
      proportion of individuals who attended for follow-up. RCTs of educational
      interventions directed at patients or health professionals were heterogeneous but
      appeared unlikely to be associated with large net reductions in blood pressure by
      themselves. Health professional (nurse or pharmacist) led care may be a promising
      way of delivering care, with the majority of RCTs being associated with improved
      blood pressure control, but requires further evaluation. AUTHORS' CONCLUSIONS:
      Family practices and community-based clinics need to have an organized system of
      regular follow-up and review of their hypertensive patients. Antihypertensive
      drug therapy should be implemented by means of a vigorous stepped care approach
      when patients do not reach target blood pressure levels.

PMID- 16625628
TI  - Interventions to promote the wearing of hearing protection.
AB  - BACKGROUND: Noise induced hearing loss can only be prevented by eliminating or
      lowering noise exposure levels. Where the source of the noise can not be
      eliminated workers have to rely on hearing protective equipment. Several trials
      have been conducted to study the effectiveness of interventions to influence the
      wearing of hearing protection and to decrease noise exposure. We aimed to
      establish whether interventions to increase the wearing of hearing protection are
      effective. OBJECTIVES: To summarise the evidence for the effectiveness of
      interventions to enhance the wearing of hearing protection among workers exposed
      to noise in the workplace. SEARCH STRATEGY: We searched the Cochrane Ear, Nose
      and Throat Disorders Group Specialised Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2005), MEDLINE (1966 to
      June 2005), EMBASE (1980 to June 2005), NIOSHTIC, CISDOC, CINAHL, LILACS (1982 to
      June 2005) and Scientific Electronic Library Online. The date of the last search
      was June 2005. SELECTION CRITERIA: Studies were included if they had a randomised
      design, if they were among noise exposed (> 80 dB(A)) workers or pupils, if there
      was some kind of intervention to promote the wearing of hearing protection
      (compared to another intervention or no intervention), and if the outcome
      measured was the amount of use of hearing protection or a proxy measure thereof.
      DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed
      methodological quality and extracted data. There were no cases where the pooling
      of data was appropriate. MAIN RESULTS: Two studies were found. One study was a
      two-phased randomised controlled trial. A computer-based intervention tailored to
      the risk of an individual worker lasting 30 minutes was not found to be more
      effective than a video providing general information among workers, around 80% of
      whom already used hearing protection. The second phase of the trial involved
      sending a reminder to the home address of participants at 30 days, 90 days or at
      both 30 and 90 days after the intervention, or no reminder. No significant
      differences in the mean use of hearing protection were found. A second randomised
      controlled trial evaluated the effect of a four year school based hearing loss
      prevention programme among pupils working at their parents farms (N=753) in a
      cluster randomised controlled trial. The intervention group was twice as likely
      to wear some kind of hearing protection as the control group that received only
      minimal intervention. All results are based on self reported use of hearing
      protection. AUTHORS' CONCLUSIONS: Limited evidence does not show whether tailored
      interventions are more or less effective than general interventions in workers,
      80% of whom already use hearing protection. Long lasting school based
      interventions may increase the use of hearing protection substantially. These
      results are based on single studies only. Better interventions to enhance the use
      of hearing protection need to be developed and evaluated in order to increase the
      prevention of noise induced hearing loss among workers.

PMID- 16625629
TI  - Risperidone versus olanzapine for schizophrenia.
AB  - BACKGROUND: Antipsychotic medication is a mainstay of treatment for
      schizophrenia. Risperidone and olanzapine are popular choices among the new
      generation drugs. OBJECTIVES: To determine the clinical effects, safety and cost
      effectiveness of risperidone compared with olanzapine for treating schizophrenia.
      SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (Sept
      2005) which is based on regular searches of, amongst others, BIOSIS, CENTRAL,
      CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were
      inspected for further trials. We also contacted relevant pharmaceutical companies
      for additional information. SELECTION CRITERIA: We included all clinical
      randomised trials comparing risperidone with olanzapine for schizophrenia and
      schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data
      independently. For homogenous dichotomous data we calculated random effects,
      relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers
      needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data,
      we calculated weighted mean differences (WMD). MAIN RESULTS: We found no
      difference for the outcome of unchanged or worse in the short term (n=548, 2
      RCTs, RR 1.00 CI 0.88 to 1.15). One study favoured olanzapine for the outcome of
      relapse/rehospitalisation by 12 months (n=279, 1 RCT, RR 2.16 CI 1.31 to 3.54,
      NNH 7 CI 3 to 25). Most mental state data showed the two drugs to be as effective
      as each other (n=552, 2 RCTs, RR 'no <20% decrease PANSS by eight weeks' 1.01 CI
      0.87 to 1.16). Both drugs commonly cause adverse events: 75% given either drug
      experience an adverse event; 20% anticholinergic symptoms; both groups
      experienced insomnia although it was more frequent with risperidone (n=1588, 5
      RCTs, RR 1.41 CI 1.15 to 1.72, NNH 15 CI 9 to 41); about 30% experienced
      sleepiness (n=1713, 6 RCTs, RR 0.92 CI 0.79 to 1.07). People given either drug
      often experienced some extrapyramidal symptoms (n=893, 3 RCTs, RR 1.18 CI 0.75 to
      1.88); 25% of people using risperidone required medication to alleviate these
      symptoms (n=419, 2 RCTs, RR 1.76 CI 1.25 to 2.48, NNH 8 CI 4 to 25). People
      allocated to risperidone were less likely to gain weight compared with those
      given olanzapine and the weight gain was often considerable and of quick onset
      (n=984, 2 RCTs, RR gain more than 7% of their baseline weight in short term 0.47
      CI 0.36 to 0.61, NNH 7 CI 6 to 10). Risperidone participants were less likely to
      leave the study due to metabolic side effects and weight gain compared with
      olanzapine (n=667, 1RCT, RR 0.19 CI 0.08 to 0.45). Patients on risperidone were
      more likely to experience abnormal ejaculation (n=370, 2 RCTs, RR 4.36 CI 1.38 to
      13.76, NNH 20 CI 6 to 176). Both drugs are associated with high attrition rates;
      in the long term consistent findings show that 66% of those allocated risperidone
      left the study early compared with 56% given olanzapine (n=1440, 5 RCTs, RR 1.17
      CI 1.08 to 1.27, NNH 11 CI 7 to 23). AUTHORS' CONCLUSIONS: We know very little of
      the effects of these drugs regarding service outcomes, general functioning and
      behaviours, engagement with services and treatment satisfaction from evaluative
      studies. There was generally a high rate of attrition in the trials and there
      appears to be little to differentiate between risperidone and olanzapine except
      on issues of adverse effects. Both drugs are associated with a reduction in
      psychotic symptoms but both commonly cause unpleasant adverse effects.

PMID- 16625630
TI  - Interventions in the alcohol server setting for preventing injuries.
AB  - BACKGROUND: Injuries are a significant public health burden and alcohol
      intoxication is recognised as a risk factor for injuries. There is increasing
      attention on supply-side interventions, which aim to modify the environment and
      context within which alcohol is supplied and consumed. OBJECTIVES: To quantify
      the effectiveness of interventions implemented in the server setting for reducing
      injuries. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised
      Register (September 2004), Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 3, 2004), MEDLINE (January 1966 to September 2004), EMBASE
      (1980 to 2004, wk 36), other specialised databases and reference lists of
      articles. We also contacted experts in the field. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and non-randomised controlled studies (NRS) of the
      effectiveness of interventions administered in the server setting which attempted
      to modify the conditions under which alcohol is served and consumed, to
      facilitate sensible alcohol consumption and reduce the occurrence of alcohol
      related harm. DATA COLLECTION AND ANALYSIS: Two authors independently screened
      search results and assessed the full texts of potentially relevant studies for
      inclusion. Data were extracted and methodological quality was examined. Due to
      variability in the intervention types investigated, a pooled analysis was not
      appropriate. MAIN RESULTS: Twenty studies met the inclusion criteria. Overall
      methodological quality was poor. Five studies used an injury outcome measure;
      only one of these studies was randomised. The studies were grouped into broad
      categories according to intervention type. One NRS investigated server training
      and estimated a reduction of 23% in single vehicle night-time crashes in the
      experimental area (controlled for crashes in the control area). Another NRS
      examined the impact of a drink driving service, and reported a reduction in
      injury road crashes of 15% in the experimental area, with no change in the
      control; no difference was found for fatal crashes. One NRS investigating the
      impact of a policy intervention, reported that pre-intervention the serious
      assault rate in the experimental area was 52% higher than the rate in the control
      area. After intervention, the serious assault rate in the experimental area was
      37% lower than in the control. The only RCT targeting the server setting
      environment with an injury outcome compared toughened glassware (experimental) to
      annealed glassware (control) on number of bar staff injuries; a greater number of
      injuries were detected in the experimental group (relative risk 1.72, 95% CI 1.15
      to 2.59). A NRS investigating the impact of a intervention aiming to reduce crime
      experienced by drinking premises; found a lower rate of all crime in the
      experimental premises (rate ratio 4.6, 95% CI 1.7 to 12, P = 0.01), no difference
      was found for injury (rate ratio 1.1. 95% CI 0.1 to 10, P = 0.093). The
      effectiveness of the interventions on patron alcohol consumption is inconclusive.
      One randomised trial found a statistically significant reduction in observed
      severe aggression exhibited by patrons. There is some indication of improved
      server behaviour but it is difficult to predict what effect this might have on
      injury risk. AUTHORS' CONCLUSIONS: There is no reliable evidence that
      interventions in the alcohol server setting are effective in reducing injury.
      Compliance with interventions appears to be a problem; hence mandated
      interventions may be more likely to show an effect. Randomised controlled trials,
      with adequate allocation concealment and blinding are required to improve the
      evidence base. Further well conducted non-randomised trials are also needed, when
      random allocation is not feasible.

PMID- 16625631
TI  - Intravenous in-line filters for preventing morbidity and mortality in neonates.
AB  - BACKGROUND: Venous access is an essential part of caring for the sick neonate;
      however, problems such as contamination of fluids with bacteria, endotoxins and
      particulates have been associated with intravenous infusion therapy. Intravenous
      in-line filters claim to be an effective strategy for the removal of bacteria,
      endotoxins and particulates associated with intravenous therapy in adults and are
      increasingly being recommended for use in neonates. OBJECTIVES: To assess whether
      in-line filters on intravenous lines prevent morbidity and mortality in neonates.
      SEARCH STRATEGY: Searches were made of the electronic databases MEDLINE (from
      1966 to September 2005), EMBASE (from 1980 to September 2005), CINAHL (from 1982
      to September 2005) and the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 3 2005 ). There was no language
      restriction. Further searching included cross references, abstracts, conferences,
      symposia proceedings, expert informants and journal handsearching. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials that compared the use
      of intravenous in-line filters with placebo or nothing in neonates were included
      in the review. DATA COLLECTION AND ANALYSIS: The procedures of the Cochrane
      Neonatal Review Group (CNRG) were followed throughout. Titles and abstracts
      identified from the search were checked by the review authors. The full text of
      all studies of possible relevance were obtained. The review authors independently
      assessed the trials for their methodological quality and subsequent inclusion in
      the review. Statistical analysis followed the procedures of the Cochrane Neonatal
      Review Group. Dichotomous data is expressed as relative risk and 95% confidence
      intervals, and risk difference and 95% confidence intervals. MAIN RESULTS: There
      were three eligible studies, which recruited a total of 262 neonates. For most of
      the outcomes for this review, only one study of 88 neonates contributed eligible
      data. This review found no significant effect of in-line filters in any of the
      reported outcomes of overall mortality, proven and unproven septicaemia,
      phlebitis, necrotizing enterocolitis, duration of cannula patency, number of
      catheters inserted and financial costs. AUTHORS' CONCLUSIONS: There are
      insufficient data to determine whether or not the use of intravenous in-line
      filters prevent morbidity and mortality in neonates. The wide confidence
      intervals on outcomes indicate the imprecise estimates of treatment effect due to
      the small numbers of patients and events.

PMID- 16625632
TI  - Iodine supplementation for the prevention of mortality and adverse
      neurodevelopmental outcomes in preterm infants.
AB  - BACKGROUND: Parenteral nutrition solutions, formula milks, and human breast milk
      contain insufficient iodine to meet recommended intakes for preterm infants.
      Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants
      and this may be associated with adverse respiratory or neurological outcomes.
      OBJECTIVES: To assess the evidence from randomised controlled trials that dietary
      supplementation with iodine reduces mortality and morbidity in preterm infants.
      SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal
      Review Group. This included searches of the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 -
      November 2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005),
      conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials that compared a policy of supplementing
      enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram per
      day) versus placebo or no supplementation in preterm infants. DATA COLLECTION AND
      ANALYSIS: The standard methods of the Cochrane Neonatal Review Group, with
      separate evaluation of trial quality and data extraction by two reviewers, and
      synthesis of data using relative risk, risk difference and weighted mean
      difference. The primary outcomes for this review were neonatal mortality, death
      before hospital discharge, and longer term neurodevelopmental outcomes including
      severe neurodevelopmental disability. MAIN RESULTS: We found only one randomised
      controlled trial (N = 121) that fulfilled the review eligibility criteria (Rogahn
      2000). The participants were infants born before 33 weeks' gestation (but most
      were of birth weight greater than 1000 grams). The primary aim of this trial was
      to assess the effect of iodine supplementation on thyroid function. The
      investigators did not detect any statistically significant effects on the plasma
      levels of thyroxine (free and total), triiodothyronine, or thyrotrophin in
      preterm infants (measured up to 40 weeks' post-conceptional age). Only one infant
      died and the trial was therefore underpowered to detect an effect on mortality.
      The trial did not assess the effect of the intervention on neurodevelopmental
      morbidity. There was not a statistically significant difference in the incidence
      of chronic lung disease. AUTHORS' CONCLUSIONS: There are insufficient data at
      present to determine whether providing preterm infants with supplemental iodine
      (to match fetal accretion rates) prevents morbidity and mortality in preterm
      infants. Future randomised controlled trials of iodine supplementation should
      focus on extremely preterm and extremely low birth weight infants, the group at
      greatest risk of transient hypothyroxinaemia. These trials should aim to assess
      the effect of iodine supplementation on clinically important outcomes including
      respiratory morbidity and longer term neurodevelopment.

PMID- 16625633
TI  - Supervised exercise therapy versus non-supervised exercise therapy for
      intermittent claudication.
AB  - BACKGROUND: Although exercise therapy is considered to be of significant benefit
      to people with leg pain (intermittent claudication), almost half of those
      affected do not undertake any exercise therapy. OBJECTIVES: To evaluate the
      effects of supervised versus non-supervised exercise therapy on the maximal
      walking time or distance for people with intermittent claudication. SEARCH
      STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their
      Specialized Register (last searched November 2005) and the Cochrane Central
      Register of Controlled Trials (CENTRAL) database in The Cochrane Library (last
      searched Issue 4, 2005). In addition, we handsearched the reference lists of
      relevant articles for additional trials. There was no restriction on language of
      publication. SELECTION CRITERIA: Randomized and controlled clinical trials
      comparing supervised exercise programs with non-supervised exercise programs for
      people with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors
      (BB and EMW) independently selected trials and extracted data. One author (BB)
      assessed trial quality and this was confirmed by a second author (MP). For all
      continuous outcomes we extracted the number of participants, the mean
      differences, and the standard deviation. If data were available, the standardized
      mean difference was calculated using a fixed-effect model. MAIN RESULTS: We
      identified twenty-seven trials, of which 19 had to be excluded because the
      control group received no exercise therapy at all. The remaining eight trials
      involved a total of 319 male and female participants with intermittent
      claudication. The follow up ranged from 12 weeks to 12 months. In general, the
      supervised exercise regimens consisted of three exercise sessions per week. All
      trials used a treadmill walking test as one of the outcome measures. The overall
      quality of the included trials was good, though the trials were all small with
      respect to the number of participants, ranging from 20 to 59. Supervised exercise
      therapy showed statistically significant and clinically relevant differences in
      improvement of maximal treadmill walking distance compared with non-supervised
      exercise therapy regimens, with an overall effect size of 0.58 (95% confidence
      interval 0.31 to 0.85) at three months. This translates to a difference of
      approximately 150 meters increase in walking distance in favor of the supervised
      group. AUTHORS' CONCLUSIONS: Supervised exercise therapy is suggested to have
      clinically relevant benefits compared with non-supervised regimens, which is the
      main prescribed exercise therapy for people with intermittent claudication.
      However, the clinical relevance has not been demonstrated definitely and will
      require additional studies with a focus on the improvements in quality of life.

PMID- 16625634
TI  - Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults
      and children.
AB  - BACKGROUND: The relative efficacy of fluticasone (FP) and beclomethasone (BDP)
      propelled with CFCs has been well established. The potency of HFA-BDP is thought
      to have been improved with new propellant and some studies suggest that it may
      equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this
      question in the light of a potentially more potent new non-CFC propellant.
      OBJECTIVES: To determine the relative efficacy of FP and HFA-propelled BDP in
      chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register
      was searched using pre-specified terms. Searches were current as of January 2006.
      SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion in
      the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We
      made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses
      smaller particles of drug, leading to different, usually more peripheral
      distribution in the airways. Any inhaler device was considered, and there was no
      restriction on studies with or without spacers. We included studies which
      assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for
      inclusion in the review. Data were extracted and entered in to RevMan 4.2 using
      standard meta-analytical techniques with predefined criteria for exploring
      statistical heterogeneity. MAIN RESULTS: Eight studies (1260 participants) met
      the inclusion criteria of the review. One study was conducted in children. Study
      reporting quality was fair, but all studies were of short duration (three to
      twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP
      were identified. Lung function was not significantly different between extra fine
      BDP and FP when compared at the same dose in parallel studies, change in FEV1:
      0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in
      am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults).
      Individual studies reported non-significant findings in symptom scores and
      quality of life questionnaires. There was no significant difference between FP
      and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported
      as any adverse event. AUTHORS' CONCLUSIONS: There was no significant difference
      between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1.
      However, the number of studies and width of the confidence intervals in the
      analyses do not exclude a clinically meaningful difference between these two
      drugs. Difficulty in the successful manipulation of the devices studied may be a
      barrier to the widespread use of MDIs. One paediatric study was included in the
      review, so extrapolation of the findings of this review to children is limited.
      Further longer term studies in adults and children with moderate and severe
      asthma are required.

PMID- 16625635
TI  - Viscosupplementation for the treatment of osteoarthritis of the knee.
AB  - BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disorder
      worldwide and is associated with significant pain and disability. OBJECTIVES: To
      assess the effects of viscosupplementation in the treatment of OA of the knee.
      The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz
      (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron,
      Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl),
      Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum).
      SEARCH STRATEGY: MEDLINE (up to January (week 1) 2006 for update), EMBASE,
      PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register
      of Controlled Trials (CENTRAL) were searched. Specialised journals and reference
      lists of identified randomised controlled trials (RCTs) and pertinent review
      articles up to December 2005 were handsearched. SELECTION CRITERIA: RCTs of
      viscosupplementation for the treatment of people with a diagnosis of OA of the
      knee were eligible. Single and double-blinded studies, placebo-based and
      comparative studies were eligible. At least one of the four OMERACT III core set
      outcome measures had to be reported (Bellamy 1997). DATA COLLECTION AND ANALYSIS:
      Each trial was assessed independently by two reviewers for its methodological
      quality using a validated tool. All data were extracted by one reviewer and
      verified by a second reviewer . Continuous outcome measures were analysed as
      weighted mean differences (WMD) with 95% confidence intervals (CI). However,
      where different scales were used to measure the same outcome, standardized mean
      differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk
      (RR). MAIN RESULTS: Seventy-six trials with a median quality score of 3 (range 1
      to 5) were identified. Follow-up periods varied between day of last injection and
      eighteen months. Forty trials included comparisons of hyaluronan/hylan and
      placebo (saline or arthrocentesis), ten trials included comparisons of intra
      articular (IA) corticosteroids, six trials included comparisons of nonsteroidal
      anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical
      therapy, two trials included comparisons of exercise, two trials included
      comparisons of arthroscopy, two trials included comparisons of conventional
      treatment, and fifteen trials included comparisons of other hyaluronans/hylan.
      The pooled analyses of the effects of viscosupplements against 'placebo' controls
      generally supported the efficacy of this class of intervention. In these same
      analyses, differential efficacy effects were observed for different products on
      different variables and at different timepoints. Of note is the 5 to 13 week post
      injection period which showed a percent improvement from baseline of 28 to 54%
      for pain and 9 to 32% for function. In general, comparable efficacy was noted
      against NSAIDs and longer-term benefits were noted in comparisons against IA
      corticosteroids. In general, few adverse events were reported in the
      hyaluronan/hylan trials included in these analyses. AUTHORS' CONCLUSIONS: Based
      on the aforementioned analyses, viscosupplementation is an effective treatment
      for OA of the knee with beneficial effects: on pain, function and patient global
      assessment; and at different post injection periods but especially at the 5 to 13
      week post injection period. It is of note that the magnitude of the clinical
      effect, as expressed by the WMD and standardised mean difference (SMD) from the
      RevMan 4.2 output, is different for different products, comparisons, timepoints,
      variables and trial designs. However, there are few randomised head-to-head
      comparisons of different viscosupplements and readers should be cautious,
      therefore, in drawing conclusions regarding the relative value of different
      products. The clinical effect for some products, against placebo, on some
      variables at some timepoints is in the moderate to large effect-size range.
      Readers should refer to relevant tables to review specific detail given the
      heterogeneity in effects across the product class and some discrepancies observed
      between the RevMan 4.2 analyses and the original publications. Overall, the
      analyses performed are positive for the HA class and particularly positive for
      some products with respect to certain variables and timepoints, such as pain on
      weight bearing at 5 to 13 weeks postinjection. In general, sample-size
      restrictions preclude any definitive comment on the safety of the HA class of
      products; however, within the constraints of the trial designs employed no major
      safety issues were detected. In some analyses viscosupplements were comparable in
      efficacy to systemic forms of active intervention, with more local reactions but
      fewer systemic adverse events. In other analyses HA products had more prolonged
      effects than IA corticosteroids. Overall, the aforementioned analyses support the
      use of the HA class of products in the treatment of knee OA.

PMID- 16625636
TI  - Intraarticular corticosteroid for treatment of osteoarthritis of the knee.
AB  - BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee,
      injections of corticosteroids into the joint (intraarticular (IA)) may relieve
      inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the
      efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 2, 2003), MEDLINE (to January (week 1) 2006 for update), EMBASE,
      PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised
      journals, trial reference lists and review articles were handsearched. SELECTION
      CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA
      of the knee: single/double blind, placebo-based/comparative studies, reporting at
      least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS:
      Methodological quality of trials was assessed, and data were extracted in
      duplicate. Fixed effect and random effects models, giving weighted mean
      differences (WMD), were used for continuous variables. Dichotomous outcomes were
      analysed by relative risk (RR). MAIN RESULTS: Twenty-eight trials (1973
      participants) comparing IA corticosteroid against placebo, against IA
      hyaluronan/hylan (HA products), against joint lavage, and against other IA
      corticosteroids, were included.IA corticosteroid was more effective than IA
      placebo for pain reduction (WMD -21.91; 95% confidence interval (CI) -29.93 to 
      13.89) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at
      one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain
      on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment.
      Data on function were sparse at one week post injection and neither statistically
      significant nor clinically important differences were detected. There was
      evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to
      3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of
      evidence for efficacy in functional improvement. At four to 24 weeks post
      injection, there was lack of evidence of effect on pain and function (small
      studies showed benefits which did not reach statistical or clinical importance,
      i.e. less than 20% risk difference). For patient global, there were three studies
      which consistently showed lack of effect longer than one week post injection.
      However, all were fairly small sample sizes (less than 50 patients per group).
      This was supported by another study which did not find statistically significant
      differences, at any time point, on a continuous measure of patient global
      assessment (100 mm VAS).In comparisons of corticosteroids and HA products, no
      statistically significant differences were in general detected at one to four
      weeks post injection. Between five and 13 weeks post injection, HA products were
      more effective than corticosteroids for one or more of the following variables:
      WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of
      responders. One study showed a difference in function between 14 to 26 weeks, but
      no differences in efficacy were detected at 45 to 52 weeks. In general, the onset
      of effect was similar with IA corticosteroids, but was less durable than with HA
      products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was
      superior to betamethasone for number of patients reporting pain reduction up to
      four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons
      between IA corticosteroid and joint lavage showed no differences in any of the
      efficacy or safety outcome measures. AUTHORS' CONCLUSIONS: The short-term benefit
      of IA corticosteroids in treatment of knee OA is well established, and few side
      effects have been reported. Longer term benefits have not been confirmed based on
      the RevMan analysis. The response to HA products appears more durable. In this
      review, some discrepancies were observed between the RevMan 4.2 analysis and the
      original publication. These are likely the result of using secondary rather than
      primary data and the statistical methods available in RevMan 4.2. Future trials
      should have standardised outcome measures and assessment times, run longer,
      investigate different patient subgroups, and clinical predictors of response
      (those associated with inflammation and structural damage).

PMID- 16625637
TI  - Prophylactic antibiotics to prevent surgical site infection after breast cancer
      surgery.
AB  - BACKGROUND: Surgery has been used as part of breast cancer treatment for
      centuries; however any surgical procedure has the potential risk of infection.
      Infection rates for surgical treatment of breast cancer are documented at between
      three and 15%, higher than average for a clean surgical procedure. Pre and peri
      operative antibiotics have been found to be useful in lowering infection rates in
      other surgical groups, yet there is no current consensus on prophylactic
      antibiotic use in breast cancer surgery. OBJECTIVES: To determine the effects of
      prophylactic antibiotics on the incidence of surgical site infection after breast
      cancer surgery. SEARCH STRATEGY: We searched the Cochrane Wounds and Breast
      Cancer Groups Specialised Registers, the Cochrane Central Register of Controlled
      Trials (CENTRAL) issue 1 2006. MEDLINE 2002-2005, EMBASE 1980-2005, NRR issue 1
      2005, CINAHL 1982-2004 and SIGLE 1976-2004. Companies and experts in the field
      were contacted and reference lists were checked. No language restrictions were
      applied. SELECTION CRITERIA: Randomised controlled trials of pre and peri
      operative antibiotics for patients undergoing surgery for breast cancer were
      included. Primary outcomes were, incidence of breast wound infection and adverse
      reactions to treatment. DATA COLLECTION AND ANALYSIS: Two authors independently
      examined the title and abstracts of all studies identified by the search
      strategy, then assessed study quality and extracted data from those that met the
      inclusion criteria. MAIN RESULTS: Six studies met the inclusion criteria. All six
      evaluated pre-operative antibiotic compared with no antibiotic or placebo.
      Pooling of the results demonstrated that prophylactic antibiotics significantly
      reduce the incidence of surgical site infection for patients undergoing breast
      cancer surgery without reconstruction (pooled RR 0.66, 95% CI, 0.48 to 0.89). No
      studies presented separate data for patients who underwent reconstructive surgery
      at the time of removal of the breast tumour. AUTHORS' CONCLUSIONS: Prophylactic
      antibiotics reduce the risk of surgical site infection in patients undergoing
      surgery for breast cancer. The potential morbidity caused by infection, such as
      delays in wound healing or adjuvant cancer treatments must be balanced against
      the cost of treatment and potential adverse effects such as drug reactions or
      increased bacterial resistance. Further studies of patients undergoing immediate
      breast reconstruction would be useful as studies have identified this group as
      being at higher risk of infection than those who do not undergo immediate breast
      reconstruction.

PMID- 16625638
TI  - Recombinant human activated protein C for severe sepsis in neonates.
AB  - BACKGROUND: Sepsis is a common problem in both preterm and term infants. Although
      the overall incidence of neonatal sepsis has declined over the past decade,
      mortality remains high. Recombinant human activated protein C (rhAPC) has been
      shown to possess a broad spectrum of activity modulating coagulation and has been
      shown in septic adults to reduce mortality. In septic children, an open label
      study has shown similar pharmacokinetics, adverse reaction profile and frequency
      as in adults with severe sepsis. OBJECTIVES: To determine whether treatment with
      rhAPC will reduce mortality and/or morbidity in neonates with severe sepsis.
      SEARCH STRATEGY: Searches were carried out in July 2005 by the review authors
      independently of MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005), CINAHL
      (1982 to July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library, Issue 3, 2005), abstracts of annual meetings of the
      Pediatric Academic Societies and Society for Pediatric Research which were
      published in Pediatric Research from 1980, and contacts were made with subject
      experts. Doctoral dissertations, theses and the Science Citation Index for
      articles on activated protein C were searched from 1980. No language restriction
      was applied. SELECTION CRITERIA: Studies were included if they were randomized or
      quasi-randomized trials, assessing the efficacy of rhAPC compared to placebo or
      no intervention as an adjunct to antibiotic therapy of suspected or confirmed
      severe sepsis in term and preterm infants less than 28 days old. Eligible trials
      were required to report treatment effects on at least one of the following
      outcomes: all cause mortality during initial hospital stay, neurological
      development and neurodevelopmental assessment at two years of age or later,
      length of hospital stay, duration of ventilation, chronic lung disease in
      survivors, periventricular leukomalacia, intraventricular hemorrhage, necrotizing
      enterocolitis, bleeding, and any other adverse events. DATA COLLECTION AND
      ANALYSIS: Both review authors independently evaluated the papers for inclusion
      criteria and quality, and abstracted information for the outcomes of interest.
      Differences were resolved by mutual discussion. The statistical methods were to
      include relative risk, risk difference, number needed to treat to benefit or
      number needed to treat to harm for dichotomous and weighed mean difference for
      continuous outcomes reported with 95% confidence intervals. A fixed effects model
      was to be used for meta-analysis. Heterogeneity tests, including the I(2)
      statistic, were to be performed to assess the appropriateness of pooling the
      data. MAIN RESULTS: No eligible trials were identified. AUTHORS' CONCLUSIONS:
      Despite the scientific rationale for its use, there are insufficient data to
      support the use of rhAPC for the management of severe sepsis in newborn infants.
      There is a need for large well-designed trials to elucidate the effectiveness of
      rhAPC to reduce mortality and adverse outcomes in neonates with severe sepsis.
      The results of such trials would guide clinical practice. Currently, a cautious
      approach to the use of rhAPC is warranted due to the high incidence of bleeding
      with its use; especially as severe sepsis in preterm infants is commonly
      associated with bleeding problems and intraventricular hemorrhage. Its use is not
      recommended outside of randomized controlled trials.

PMID- 16625639
TI  - Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant
      pulmonary tuberculosis.
AB  - BACKGROUND: The emergence and spread of multiple-drug-resistant tuberculosis (MDR
      TB), caused by strains of Mycobacterium tuberculosis resistant to at least
      isoniazid and rifampicin, is a potential threat to global tuberculosis control.
      Treatment is prolonged, expensive, more toxic than treatment of susceptible
      tuberculosis, and often unsuccessful. Experts are still undecided on the
      management of people exposed to MDR-TB. OBJECTIVES: To evaluate antituberculous
      drugs given to people exposed to MDR-TB in preventing active tuberculosis. SEARCH
      STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register
      (January 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to
      January 2006); EMBASE (1974 to January 2006), LILACS (1982 to January 2006),
      conference proceedings, and reference lists. We also contacted researchers and
      organizations. SELECTION CRITERIA: Randomized controlled trials comparing
      antituberculous drug regimens with an alternative antituberculous drug regimen,
      placebo, or no intervention given to people exposed to MDR-TB for preventing
      active tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently
      inspected titles and abstracts identified by the search in order to identify
      potentially relevant publications for inclusion and analysis. MAIN RESULTS: No
      randomized controlled trials met the inclusion criteria. AUTHORS' CONCLUSIONS:
      The balance of benefits and harms associated with treatment for latent
      tuberculosis infection in people exposed to MDR-TB is far from clear.
      Antituberculous drugs should only be offered within the context of a well
      designed randomized controlled trial, or when people are given the details of the
      current evidence on benefits and harms, along with the uncertainties.

PMID- 16625640
TI  - Laetrile treatment for cancer.
AB  - BACKGROUND: Laetrile is an unconventional therapy which has been used illegally
      for decades by cancer patients who together with some alternative therapists
      claim its effectiveness as an anti-cancer treatment. It has been often referred
      to as amygdalin, although the two are not the same. OBJECTIVES: The aim of this
      review was to assess the alleged anti-cancer effect and the possible harms of
      Laetrile as a sole or adjunctive therapy in cancer treatment. SEARCH STRATEGY: We
      searched The Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE
      (from 1951); EMBASE (from 1980); Allied and Complementary Medicine (AMED),
      Scirus, CancerLit, CINAHL (all from 1982); CAMbase (from 1998); the MetaRegister;
      the National Research Register and our own files. No language restrictions were
      imposed. SELECTION CRITERIA: Randomized clinical trials (RCTs) and non randomized
      controlled clinical trials (non-RCTs). DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trials for inclusion in the review, assessed
      study quality and extracted data. MAIN RESULTS: No RCTs or non-RCTs were found,
      so no abstraction of outcome data could be performed in this systematic review
      AUTHORS' CONCLUSIONS: The claim that Laetrile has beneficial effects for cancer
      patients is not supported by data from controlled clinical trials. This
      systematic review has clearly identified the need for randomised or controlled
      clinical trials assessing the effectiveness of Laetrile or amygdalin for cancer
      treatment.

PMID- 16625641
TI  - Tongue scraping for treating halitosis.
AB  - BACKGROUND: Halitosis is used to describe any disagreeable odour of expired air
      regardless of its origin. Mouthwashes which disguise oral malodor are more
      socially acceptable and generally more popular than tongue scrapers. OBJECTIVES:
      To provide reliable evidence regarding the effectiveness of tongue scraping
      versus other interventions (including mouthwashes) to control halitosis. SEARCH
      STRATEGY: We searched the following databases: Cochrane Oral Health Group Trials
      Register (to 15th September 2005); the Cochrane Central Register of Controlled
      Trials (The Cochrane Library, Issue 3 2005); MEDLINE 1966 to September Week 1
      2005; EMBASE 1974 to September 2005 (searched September 19th 2005). SELECTION
      CRITERIA: Randomized controlled trials comparing different methods of tongue
      cleaning to reduce mouth odour in adults with halitosis. DATA COLLECTION AND
      ANALYSIS: Clinical heterogeneity between the two included trials precluded
      pooling of data, therefore a descriptive summary is presented. MAIN RESULTS: This
      review included two trials involving 40 participants. Both trials were
      methodologically sound but included no data for the primary outcomes specified in
      this review. Secondary outcomes expressed as volatile sulfur compound (VSC)
      levels were assessed by a portable sulfide monitor in both trials. One trial
      showed reductions of VSC levels of 42% with the tongue cleaner, 40% with the
      tongue scraper and 33% with the toothbrush. Reduced VSC levels persisted longer
      with the tongue cleaner than the toothbrush and could not be detected for more
      than 30 minutes after the intervention in any of the groups. Differences were
      assessed by the Friedman and Wilcoxon signed rank tests with the level of
      significance set at P < 0.05. The second trial, in which differences in totaled
      rank values between groups were compared by the Dunn method alpha = 0.01, showed
      a reduction of VSC levels compared with baseline measurements of 75% with the
      tongue scraper and 45% with the toothbrush. Adverse effects in one trial were
      nausea (60%) and trauma (10%) with the toothbrush and all participants receptive
      to using the tongue scraper. Based on the independent data from these two trials
      there was a statistically significant difference between the effectiveness of
      either the tongue cleaner or the tongue scraper in reducing VSC levels when
      compared with the toothbrush. AUTHORS' CONCLUSIONS: There is weak and unreliable
      evidence to show that there is a small but statistically significant difference
      in reduction of VSC levels when tongue scrapers or cleaners rather than
      toothbrushes are used to reduce halitosis in adults. We found no high level
      evidence comparing mechanical with other forms of tongue cleaning.

PMID- 16625642
TI  - Chinese medicinal herbs for measles.
AB  - BACKGROUND: Measles is an infectious disease caused by Morbillivirus. Chinese
      physicians believe that medicinal herbs are effective in alleviating symptoms and
      preventing complications. Chinese herbal medicines are dispensed according to the
      particular symptoms. OBJECTIVES: To assess the effectiveness and possible adverse
      events of Chinese medicinal herbs in treating measles. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Clinical Trials (CENTRAL)
      (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to June 2005); EMBASE (1980
      to June 2005); the Chinese Biomedical Database (1976 to June 2005); VIP
      Information (1989 to June 2005); China National Knowledge Infrastructure (CNKI)
      (1994 to June 2005); and the metaRegister of Controlled Trials was searched for
      ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which
      patients with measles without complications were treated with Chinese medicinal
      herbs were included. DATA COLLECTION AND ANALYSIS: The primary outcome measure
      was death from any cause. The secondary outcome measure was improvement of
      overall symptoms. The tertiary outcome measure was fever clearance time. MAIN
      RESULTS: We identified 28 trials which claimed to use random allocation. Nineteen
      study authors were contacted by telephone and we discovered that the allocation
      methods they had used were not actually randomised. Three studies were excluded
      because the patients experienced complications. We were unable to contact the
      remaining six authors. These require further assessment and have been allocated
      to the 'Studies awaiting assessment' section. AUTHORS' CONCLUSIONS: Two authors
      independently assessed trial quality and extracted data. We interviewed by
      telephone the study authors for missing information regarding random allocation
      of the study process. Some trials allocated the participants according to the
      sequence they were admitted to the trials, that is to say, by using a pseudo
      random allocation method. None of the trials concealed the allocation or blinding
      method. We hope future randomised controlled trials (RCTs) in this field will be
      conducted.

PMID- 16625643
TI  - Leukotriene receptor antagonist for prolonged non-specific cough in children.
AB  - BACKGROUND: Non-specific cough is defined as non-productive cough in the absence
      of identifiable respiratory disease or known aetiology. It is commonly seen in
      paediatric practice. These children are treated with a variety of therapies
      including a variety of asthma medications. The leukotriene pathway is reported to
      be involved in the sensory (neurogenic) pathway, which is a mechanism thought to
      be involved in the pathogenesis of chronic cough. OBJECTIVES: To evaluate the
      effectiveness of leukotriene receptor antagonist (LTRA) in treating children with
      prolonged non-specific cough. SEARCH STRATEGY: The Cochrane Register of
      Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register,
      MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The
      latest searches were carried out in September 2005. SELECTION CRITERIA: All
      randomised controlled trials comparing LTRA with a placebo medication in children
      with non-specific cough. DATA COLLECTION AND ANALYSIS: Results of searches were
      reviewed against pre-determined criteria for inclusion. One eligible trial was
      identified but no data was available for analysis. It was not possible to
      separate results from children with non-specific cough from those without. MAIN
      RESULTS: There was no significant difference in all study endpoints between the
      montelukast and placebo groups (total N=256). AUTHORS' CONCLUSIONS: With the lack
      of evidence, the routine use of LRTA in treating children with non-specific cough
      cannot be recommended.

PMID- 16625644
TI  - Rest during pregnancy for preventing pre-eclampsia and its complications in women
      with normal blood pressure.
AB  - BACKGROUND: Women at risk of pre-eclampsia or gestational hypertension are
      sometimes advised to rest. Whether this, overall, does more good than harm is
      unclear. OBJECTIVES: To assess the effects of rest or advice to reduce physical
      activity during pregnancy for preventing pre-eclampsia and its complications in
      women with normal blood pressure. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), and
      EMBASE (2002 to August 2005). SELECTION CRITERIA: Studies were included if they
      were randomised trials evaluating the effects of rest or advise to reduce
      physical activity for preventing pre-eclampsia and its complications in women
      with normal blood pressure. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials for inclusion and extracted data. Data were double
      checked for accuracy. MAIN RESULTS: Two small trials (106 women) of uncertain
      quality were included. Both recruited women with a singleton pregnancy at
      moderate risk of pre-eclampsia from 28 to 32 weeks' gestation. There was a
      statistically significant reduction in the relative risk of pre-eclampsia with
      four to six hours rest per day (one trial, 32 women; relative risk (RR) 0.05, 95%
      confidence interval (CI) 0.00 to 0.83), but not of gestational hypertension (RR
      0.25, 95% CI 0.03 to 2.00), compared to normal activity. Rest of 30 minutes per
      day plus nutritional supplementation was associated with a reduction in the risk
      of pre-eclampsia (one trial, 74 women; RR 0.13, 95% CI 0.03 to 0.51) and also of
      gestational hypertension (RR 0.15, 95% CI 0.04 to 0.63). The effect on caesarean
      section was unclear (RR 0.82, 95% CI 0.48 to 1.41). No other outcomes were
      reported. AUTHORS' CONCLUSIONS: Daily rest, with or without nutrient
      supplementation, may reduce the risk of pre-eclampsia for women with normal blood
      pressure, although the reported effect may reflect bias and/or random error
      rather than a true effect. There is no information about outcomes such as
      perinatal mortality and morbidity, maternal morbidity, women's views, adverse
      effects, and costs. Current evidence is insufficient to support recommending rest
      or reduced activity to women for preventing pre-eclampsia and its complications.
      Whether women rest during pregnancy should therefore be a matter of personal
      choice.

PMID- 16625645
TI  - Exercise or other physical activity for preventing pre-eclampsia and its
      complications.
AB  - BACKGROUND: The association between an increase in regular physical activity and
      a reduction in the risk of hypertension is well documented for non-pregnant
      people. It has been suggested that exercise may help prevent pre-eclampsia and
      its complications. Possible adverse effects of increased physical activity during
      pregnancy, particularly on the risk of preterm birth and fetal growth
      restriction, are unclear. It is, therefore, important to assess whether exercise
      reduces the risk of pre-eclampsia and its complications and, if so, whether these
      benefits outweigh the risks. OBJECTIVES: To assess the effects of exercise, or
      increased physical activity, on prevention of pre-eclampsia and its
      complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group Trials Register (December 2005), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2005, Issue 1), and EMBASE (2002 to
      February 2005). SELECTION CRITERIA: Studies were included if these were
      randomised trials evaluating the effects of exercise or increased physical
      activity during pregnancy for women at risk of pre-eclampsia. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials for inclusion and
      extracted data. Data were entered on Review Manager software for analysis, and
      double checked for accuracy. MAIN RESULTS: Two small, good quality trials (45
      women) were included. Both compared moderate intensity regular aerobic exercise
      with maintenance of normal physical activity during pregnancy. The confidence
      intervals were wide and crossed the line of no effect for all reported outcomes
      including pre-eclampsia (relative risk 0.31, 95% confidence interval 0.01 to
      7.09). AUTHORS' CONCLUSIONS: There is insufficient evidence for reliable
      conclusions about the effects of exercise on prevention of pre-eclampsia and its
      complications.

PMID- 16625646
TI  - Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum
      malaria.
AB  - BACKGROUND: The World Health Organization recommends artemether-lumefantrine, an
      expensive drug, as a treatment for uncomplicated malaria. We sought evidence of
      the superiority of the four-dose regimen over existing treatments. OBJECTIVES: To
      evaluate the four-dose regimen of artemether-lumefantrine for treating
      uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The
      Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to
      October 2005), LILACS (1982 to October 2005), conference proceedings, and
      reference lists of articles. We also contacted experts in malaria research and
      the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION
      CRITERIA: Randomized controlled trials comparing four doses of artemether
      lumefantrine with standard treatment regimens (single drug or combination), or
      six doses of artemether-lumefantrine, for treating uncomplicated falciparum
      malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied
      inclusion criteria to potentially relevant trials, assessed trial quality, and
      extracted data, including adverse events. Total failure by day 28 (day 42 for
      sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome.
      MAIN RESULTS: Seven trials (2057 participants) tested a four-dose regimen. More
      people tended to fail treatment with artemether-lumefantrine than with other
      drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial),
      halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1
      trial; difference statistically significant for mefloquine). When compared with
      chloroquine, artemether-lumefantrine was better in two trials (378 participants),
      but over 50% of the participants treated with chloroquine had total failure by
      day 28. Fewer people failed treatment with the six-dose regimen compared to the
      four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial).
      AUTHORS' CONCLUSIONS: The four-dose regimen of artemether-lumefantrine seems to
      be less effective than regimens against which it has been tested. The six-dose
      regimen is superior to four-dose regimen.

PMID- 16625647
TI  - Vaccines for preventing malaria (SPf66).
AB  - BACKGROUND: A malaria vaccine is badly needed. SPf66 was one of the earliest
      vaccines developed. It is a synthetic peptide vaccine containing antigens from
      the blood stages of malaria linked together with an antigen from the sporozoite
      stage, and is targeted mainly against the blood (asexual) stages. OBJECTIVES: To
      assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P.
      vivax, P. malariae, and P. ovale in preventing infection, disease, and death.
      SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized
      Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE
      (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to
      September 2005), Science Citation Index (1981 to September 2005), and reference
      lists of articles. We also contacted organizations and researchers in the field.
      SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing
      SPf66 vaccine with placebo or routine antimalarial control measures in people of
      any age receiving an artificial challenge or natural exposure to malaria
      infection (any species). DATA COLLECTION AND ANALYSIS: Two people independently
      assessed trial quality and extracted data, including adverse events. Results were
      expressed as relative risks (RR) with 95% confidence intervals (CI). MAIN
      RESULTS: Ten efficacy trials of SPf66 involving 9698 participants were included.
      Results with SPf66 in reducing new episodes of P. falciparum malaria were
      heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90
      to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25;
      1221 participants). In four trials in South America the number of first attacks
      with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807
      participants). It did not reduce episodes of P. vivax malaria or admission to
      hospital with severe malaria. Trials have not indicated any serious adverse
      events with SPf66 vaccine. AUTHORS' CONCLUSIONS: There is no evidence for
      protection by SPf66 vaccines against P. falciparum in Africa. There is a modest
      reduction in attacks of P. falciparum malaria following vaccination with SPf66 in
      South America. There is no justification for further trials of SPf66 in its
      current formulation. Further research with SPf66 vaccines in South America or
      with new formulations of SPf66 may be justified.

PMID- 16625648
TI  - Pharmaceutical policies: effects of reference pricing, other pricing, and
      purchasing policies.
AB  - BACKGROUND: Pharmaceuticals can be important for people's health. At the same
      time drugs are major components of health care costs. Pharmaceutical pricing and
      purchasing policies are used to determine or affect the prices that are paid for
      drugs. Examples are price controls, maximum prices, price negotiations, reference
      pricing, index pricing and volume-based pricing policies. The essence of
      reference pricing is to establish a maximum level of reimbursement for a group of
      drugs assumed to be therapeutically equivalent. OBJECTIVES: To determine the
      effects of pharmaceutical pricing and purchasing policies on drug use, healthcare
      utilisation, health outcomes and costs (expenditures). SEARCH STRATEGY: We
      searched the following databases and web sites: Effective Practice and
      Organisation of Care Group Register (date of last search: 22/08/03), Cochrane
      Central Register of Controlled Trials (15/10/03), MEDLINE (07/09/05), EMBASE
      (07/09/05), ISI Web of Science (08/09/05), CSA Worldwide Political Science
      Abstracts (21/10/03), EconLit (23/10/03), SIGLE (12/11/03), INRUD (21/11/03),
      PAIS International (23/03/04), International Political Science Abstracts
      (09/01/04), NHS EED (20/02/04), PubMed (25/02/04), NTIS (03/03/04), IPA
      (22/04/04), OECD Publications & Documents (30/08/05), SourceOECD (30/08/05),
      World Bank Documents & Reports (30/08/05), World Bank e-Library (04/05/05), JOLIS
      (22/08/05), Global Jolis (22/08/05 and 23/08/05), WHOLIS (29/08/05). SELECTION
      CRITERIA: Policies in this review were defined as laws, rules, financial and
      administrative orders made by governments, non-government organisations or
      private insurers. To be included a study had to include an objective measure of
      at least one of the following outcomes: drug use, healthcare utilisation, health
      outcomes, and costs (expenditures); the study must be a randomised controlled
      trial, non-randomised controlled trial, interrupted time series analysis,
      repeated measures study or controlled before-after study of a pharmaceutical
      pricing or purchasing policy for a large jurisdiction or system of care. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed
      study limitations. Quantitative analysis of time series data, for studies with
      sufficient data, and qualitative analyses were undertaken. MAIN RESULTS: We
      included 10 studies of reference pricing and one study of index pricing. Most of
      the reference pricing studies were for senior citizens in British Columbia,
      Canada. The use (dispensing) of reference drugs increased in five studies,
      between 60% and 196% immediately after introduction of reference drug pricing,
      whereas the use of cost sharing drugs decreased by between 19% and 42% in four
      studies. In three studies the reference drug group expenditures decreased (range
      19% - 50%), whereas in the fourth study the expenditures increased by 5% in the
      short term. The results after six months of reference pricing do not show any
      clear pattern in relationship to the immediate effects. We found no evidence of
      adverse effects on health and no clear evidence of increased health care
      utilisation. For index pricing the evidence was much more limited than for
      reference drug pricing. A small reduction in drug prices was found. AUTHORS'
      CONCLUSIONS: We found relatively few studies of pricing policies. The majority of
      the studies dealt with reference pricing. They had few methodological
      limitations. Based on the evidence in this review, mostly from senior citizens in
      British Columbia, Canada, reference drug pricing can reduce third party drug
      expenditures by inducing a shift in drug use towards less expensive drugs. We
      found no evidence of adverse effects on health and no clear evidence of increased
      health care utilisation. The analysis and reporting of the effects on patient
      drug expenditures were limited in the included studies and administration costs
      were not reported.

PMID- 16625649
TI  - Nicobrevin for smoking cessation.
AB  - BACKGROUND: Nicobrevin is a proprietary product marketed as an aid to smoking
      cessation. It contains quinine, menthyl valerate, camphor and eucalyptus oil.
      OBJECTIVES: The objective of this review was to assess the effects of Nicobrevin
      on long term smoking cessation SEARCH STRATEGY: We searched the Cochrane Tobacco
      Addiction Group trials register. SELECTION CRITERIA: Randomized trials comparing
      Nicobrevin to placebo or an alternative therapeutic control, which reported
      smoking cessation with at least six months follow up. DATA COLLECTION AND
      ANALYSIS: Data were sought on the outcome, method of randomization, and
      completeness of follow up. MAIN RESULTS: We identified no trials meeting the full
      inclusion criteria including long-term follow up. AUTHORS' CONCLUSIONS: There is
      no evidence available from long-term trials that Nicobrevin can aid smoking
      cessation.

PMID- 16625650
TI  - Adjuvant chemotherapy for invasive bladder cancer (individual patient data).
AB  - BACKGROUND: Controversy exists as to whether adjuvant chemotherapy improves
      survival in patients with invasive bladder cancer, despite a number of randomised
      controlled trials. OBJECTIVES: To evaluate the effect of adjuvant chemotherapy in
      invasive bladder cancer. We conducted a systematic review and meta-analysis of
      updated individual patient data from all available randomised controlled trials
      comparing local treatment plus adjuvant chemotherapy versus the same local
      treatment alone. SEARCH STRATEGY: MEDLINE and Cancerlit searches were
      supplemented with information from registers and hand searching meeting
      proceedings and also by discussion with relevant trialists and organisations.
      They have been regularly updated until September 2004. SELECTION CRITERIA: Trials
      that aimed to randomise patients with biopsy proven invasive (i.e. clinical stage
      T2-T4a) transitional cell carcinoma of the bladder to receive local definitive
      treatment with or without adjuvant chemotherapy were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: We collected, validated and re-analysed updated data on
      all randomised patients from all available randomised trials, including 491
      patients from 6 RCTs. For all outcomes, we obtained overall pooled hazard ratios
      using the fixed effects model. To explore the potential impact of trial design,
      we pre-planned analyses that grouped trials by important aspects of their design
      that might influence the treatment effect. To investigate any differences in
      effect by pre-defined patient sub-groups, we used a stratified logrank analysis
      on the primary endpoint of survival. MAIN RESULTS: Analyses were based on 491
      patients from six trials, representing 90% of all patients randomised in
      cisplatin-based combination chemotherapy trials and 66% of patients from all
      eligible trials. The power of this meta-analysis is clearly limited. The overall
      hazard ratio for survival of 0.75 (95%CI 0.60-0.96, p=0.019) suggests a 25%
      relative reduction in the risk of death for chemotherapy compared to that on
      control. Cox regression suggests that small imbalances in patient characteristics
      do not bias the results in favour of chemotherapy. However, the impact of trials
      that stopped early, of patients not receiving allocated treatments or not
      receiving salvage chemotherapy is less clear. AUTHORS' CONCLUSIONS: This IPD meta
      analysis provides the best evidence currently available on the role of adjuvant
      chemotherapy for invasive bladder cancer. However, at present there is
      insufficient evidence on which to reliably base treatment decisions. These
      results highlight the urgent need for further research into the use of adjuvant
      chemotherapy. The results of appropriately sized randomised trials, such as the
      ongoing EORTC-30994 trial are needed before any definitive conclusions can be
      drawn.

PMID- 16625651
TI  - Cranial suture complexity in white-tailed deer (Odocoileus virginianus).
AB  - Neurocranial expansion and mastication are commonly implicated as the two major
      biomechanical factors affecting suture morphology. In deer the antlers provide an
      additional source of biomechanical stress acting on the skull. Equivalent
      stresses are not found in females, who lack antlers. We analyzed the complexity
      and interdigitation of the interfrontal and coronal sutures that surround the
      antler-bearing frontal bones of (n = 67) white-tailed deer (Odocoileus
      virginianus) to 1) evaluate changes in suture morphology throughout ontogeny, and
      2) test the hypothesis that male deer have more complex sutures than females. Two
      methods were used to quantify suture morphology: fractal analysis and length
      ratios (actual suture length divided by direct straightline length). Both
      techniques produced similar results, although the two methods cannot be
      considered equivalent. Suture complexity increases markedly throughout ontogeny,
      but appears to level off after animals have reached adulthood. Cranial size in
      males, but not females, continues to increase in adults. No significant increase
      in suture complexity with age in the adult cohort was detected. While deer are
      highly dimorphic in size and the presence of antlers, no significant differences
      existed between males and females for any measure of suture complexity. No
      consistent patterns emerged between suture complexity and skull size or antler
      characteristics. The presence of antlers appears to have a minimal effect on
      suture complexity in white-tailed deer. Factors that may contribute to the lack
      of dimorphism in suture complexity are discussed.

PMID- 16625652
TI  - The role of mass spectrometry in the study of non-enzymatic protein glycation in
      diabetes: an update.
AB  - Recent studies on non-enzymatic protein glycation are reviewed, and results are
      critically discussed. Advanced glycation end products (AGE) levels in the body
      reflect a balance between their formation and catabolism. AGE proteolysis leads
      to the formation of low-molecular-weight AGE (AGE peptides) that are normally
      excreted in urine. In the case of diabetic disease and/or renal failure, AGE
      peptides accumulate in plasma. Because of their high reactivity, these compounds
      have been thought to play a role in the progression of chronic complications. The
      structural identification of these compounds is particularly important, and a
      strategy has been designed for their possible definition. A series of experiments
      has been devoted to the study of the enzymatic degradation products of in vitro
      glycated human serum albumin (HSA). This approach, based on different MS methods
      (LC/ESI/MS, LC/ESI/FTMS, MALDI), led to the detection of the glycated peptides
      generated by digestion of HSA. A further study was devoted to the possible
      identification of the peptides identified in the glycated HSA digestion products
      in the plasma of diabetic and nephropatic subjects. No glycated HSA digestion
      products were found in plasma samples of the subjects under investigation even if
      clear differences were found among the LC runs from populations of healthy,
      diabetic, and nephropatic subjects. Parallel investigations were devoted to the
      evaluation of glyoxal and methylglyoxal-dicarbonyl compounds that originate at
      the intermediate stage of the Maillard reaction. This evaluation was performed in
      diabetic patients, before and after the achievement of good metabolic control,
      and in nephropatic patients subjected to peritoneal dialysis (PD). In the latter
      case, results indicated that these dicarbonyl compounds, already present in the
      dialysis fluids, show a decrease in plasma and in dialysis fluids; those data
      suggested their reaction at peritoneal membrane level.

PMID- 16625653
TI  - Effect of cationized gelatins on the paracellular transport of drugs through caco
      2 cell monolayers.
AB  - Cationized gelatins, candidate absorption enhancers, were prepared by addition of
      ethylenediamine or spermine to gelatin and the effects of the resulting
      ethylenediaminated gelatin (EG) and sperminated gelatin (SG) on the paracellular
      transport of 5(6)-carboxyfluorescein (CF), FITC-dextran-4 (FD4), and insulin
      through caco-2 cell monolayers were examined. The Renkin function was used for
      characterization of the paracellular pathway and changes in the pore radius (R)
      and pore occupancy/length ratio (epsilon/L) calculated from the apparent
      permeability coefficients (P(app)) of CF and FD4 are discussed.
      Ethylenediaminetetraacetic acid (EDTA) increased the R of the caco-2 cell
      monolayer and the P(app) of all compounds examined was markedly increased by the
      addition of EDTA. On the other hand, EG and SG did not increase R and their
      enhancing effects were not as strong as those of EDTA. The increase in epsilon/L
      could be the enhancing mechanism for the cationized gelatins. The number of
      pathways for water-soluble drugs, such as CF and FD4, in the caco-2 monolayers
      could be increased by the addition of the cationized gelatins. The ratios of the
      permeability coefficients of insulin (observed/calculated based on the Renkin
      function) suggest that insulin undergoes enzymatic degradation during transport
      which is not inhibited by enhancers.

PMID- 16625654
TI  - Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in
      rats.
AB  - We carried out a pharmacokinetic study to determine the levels and profiles of
      catechins in pregnant rats and their fetuses after ingestion of green tea extract
      (GTE). We measured total catechin levels after enzyme digestions. Dams, at 15.5
      days of gestation, were fed with GTE and catechins were measured in the maternal
      plasma, placenta, and fetus 0, 0.5, 1, 2, 3, 5, 8, 10, 12, 16, and 20 h after
      maternal GTE intake. The pharmacokinetic changes were analyzed by non
      compartmental models. We found that maternal plasma concentrations of catechins
      were about 10 times higher than in placenta and 50-100 times higher than in the
      fetus. AUC and Cmax levels of (-)-epicatechin (EC) were the highest in plasma
      while the levels of (-)-epigallocatechin gallate (EGCG) were the highest in the
      placenta and the fetus. The exposure level of catechin derivatives was higher
      than the gallate derivatives in maternal plasma after normalization but reversed
      in the placenta and fetus. The absorption of epi-isomers in plasma was found to
      be more favorable than their non epi-isomer counterparts. EGCG had the highest
      level of exposure (AUC) and the highest Cmax in the fetus, implying it may have
      potential for in utero antioxidant protection.

PMID- 16625655
TI  - Solid state interactions between the proton pump inhibitor omeprazole and various
      enteric coating polymers.
AB  - The influence of the acidic film formers Eudragit L 100, HPMCAS-HF, HP-55, and
      shellac on the stability of the acid-labile proton pump inhibitor omeprazole in
      solid drug-polymer blends at accelerated storage conditions (40 degrees C/75% RH)
      was determined by fourier transform infrared spectroscopy (FTIR), modulated
      temperature differential scanning calorimetry (MTDSC), and high performance
      liquid chromatography (HPLC). As expected, acidic polymers caused a degradation
      of omeprazole which was manifested by discolorations and increasing amounts of
      degradation products. However, MTDSC curves and FTIR spectra did not show
      additional peaks resulting from the omeprazole degradation products. These
      methods appeared to be not sensitive enough to separate analytically the drug and
      polymer signals from those of the decomposition products. With HPLC a sufficient
      quantification of the degradation products was possible. HP-55 caused the highest
      degree of omeprazole degradation, followed by shellac, HPMCAS-HF, and Eudragit L
      100. No correlation with the microenvironmental pH values generated by the acidic
      polymers at the applied storage conditions was found. The melting process and the
      dissolution of acidic impurities were figured out as possible reasons for the
      more pronounced decomposition of the drug in presence of HP-55 and shellac.

PMID- 16625656
TI  - Effect of design on the performance of a dry powder inhaler using computational
      fluid dynamics. Part 2: Air inlet size.
AB  - This study investigates the effect of air inlet size on (i) the flowfield
      generated in a dry powder inhaler, and (ii) the device-specific resistance, and
      the subsequent effect on powder deagglomeration. Computational fluid dynamics
      (CFD) analysis was used to simulate the flowfield generated in an Aerolizer with
      different air inlet sizes at 30, 45, and 60 l/min. Dispersion performance of the
      modified inhalers was measured using mannitol powder and a multistage liquid
      impinger at the same flow rates. The air inlet size had a varying effect on
      powder dispersion depending on the flow rate. At low flow rates (30 and 45
      l/min), reducing the air inlet size increased the inhaler dispersion performance
      by increasing the flow turbulence and particle impaction velocities above their
      critical levels for maximal powder dispersion. At 60 l/min, reducing the air
      inlet size reduced the inhaler dispersion performance by releasing a large amount
      of powder from the device before the turbulence levels and particle impaction
      velocities could be fully developed. The results demonstrate that the maximal
      inhaler dispersion performance can be predicted if details of the device
      flowfield are known.

PMID- 16625657
TI  - Conformational structure, dynamics, and solvation energies of small alanine
      peptides in water and carbon tetrachloride.
AB  - The rate-limiting barrier for peptide transport across lipid bilayers is the
      nonpolar hydrocarbon interior. Permeating peptides may undergo conformational
      changes during their transfer from an aqueous solution into the barrier domain,
      thus facilitating peptide transport. To test this hypothesis, all-atom and
      explicit-solvent molecular dynamics (MD) simulations have been conducted on a
      series of small peptides, p-toluyl-Ala(n) (n = 0-3) used previously in transport
      experiments, to explore their conformational structures, dynamics and solvation
      free energies in water and carbon tetrachloride (CCl(4)). The conformations of
      the p-toluyl alanine di- and tri-peptides in water were found to be far from
      random coils, with P(II) and alpha(R) dominating but with smaller populations of
      seven-membered (c(7)) and five-membered rings (c(5)). In contrast, the seven
      membered ring, c(7), along with c(5) dominated in CCl(4). These results indicate
      that the conformational preferences of the alanine peptides are highly sensitive
      to solvent. Dynamically, stable seven-membered ring formation occurred on a time
      scale of 10 ps while larger ring-sizes (e.g., 10-membered rings) were observed
      much less frequently. The values of adjacent torsional angles (phi(1), psi(1))
      were dependent on neighboring torsional angles. Thermal motions of neighboring
      torsions leading to transitions between c(7), c(5), alpha(R), and P(II)
      conformers were highly cooperative while longer range correlations between
      transitions of adjacent sets of torsions (phi(1), psi(1)) and (phi(2), psi(2))
      were less evident. Peptide folding in CCl(4) lowers the intramolecular
      electrostatic energies. This, along with hydrophobic interactions, favors
      partitioning into CCl(4). These effects only partially offset other types of
      intramolecular interactions and peptide-solvent polar interactions that are more
      favorable in water, leading to net transfer free energies (3-7 kcal/mol) that
      disfavor peptide transfer from water into carbon tetrachloride.

PMID- 16625658
TI  - In vivo use of the P450 inactivator 1-aminobenzotriazole in the rat: varied
      dosing route to elucidate gut and liver contributions to first-pass and systemic
      clearance.
AB  - The small intestine is regarded as an absorptive organ in the uptake of orally
      administered drugs, but also has the ability to metabolize drugs by both phase 1
      and phase 2 reactions. The amount of drug that reaches the systemic circulation
      can be reduced by both intestinal and hepatic metabolism. 1-Aminobenzotriazole
      (ABT) is an irreversible inhibitor of cytochrome P450s. Through in vivo and in
      vitro studies, ABT has been evaluated for its utility in studying intestinal
      metabolism in rats. Rats have been exposed to ABT through varied routes of
      administration followed by p.o. and i.v. administration of midazolam (MDZ), a
      CYP3A substrate. The MDZ bioavailablity in rats dosed orally and in rats dosed
      intravenously with ABT is 58.5% and 0.7%, respectively (%F = 2.3% w/o ABT). The
      approximately 80-fold difference between the two groups suggests the majority of
      the extraction occurs in the intestine following an oral dose. To further study
      the utility of ABT, the antihistamine fexofenadine (Fex), which is not
      significantly metabolized and is a substrate for the uptake and efflux
      transporters, OATP and P-gp, was tested in rat. There was no change in oral or
      systemic exposure of Fex when animals were predosed with ABT, suggesting that ABT
      does not affect these transporters. These findings may lead to a better
      understanding of the interdependent role of absorption and metabolism and the
      specificity of ABT. This method should have utility in drug discovery for the
      identification of factors limiting oral bioavailability.

PMID- 16625659
TI  - Therapeutic utility of a novel tight junction modulating peptide for enhancing
      intranasal drug delivery.
AB  - Previously, a novel tight junction modulating (TJM) peptide was described
      affording a transient, reversible lowering of transepithelial electrical
      resistance (TER) in an in vitro model of nasal epithelial tissue. In the current
      report, this peptide has been further evaluated for utility as an excipient in
      transepithelial drug formulations. Chemical stability was optimal at neutral to
      acidic pH when stored at or below room temperature, conditions relevant to
      therapeutic formulations. The TJM peptide was tested in the in vitro tissue model
      for potential to enhance permeation of a low-molecular-weight (LMW) drug, namely
      the acetylcholinesterase inhibitor galantamine, as well as three peptides, salmon
      calcitonin, parathyroid hormone 1-34 (PTH(1-34)), and peptide YY 3-36 (PYY(3
      36)). In all cases, the TJM peptide afforded a dramatic improvement in drug
      permeation across epithelial tissue. In addition, a formulation containing PYY(3
      36) and TJM peptide was dosed intranasally in rabbits, resulting in a dramatic
      increase in bioavailability. The TJM peptide was as or more effective in
      enhancing PYY(3-36) permeation in vivo at a 1000-fold lower molar concentration
      compared to using LMW enhancers. Based on these in vitro and in vivo data, the
      novel TJM peptide represents a promising advancement in intranasal formulation
      development.

PMID- 16625660
TI  - Nitric oxide and peroxynitrite induce cellular death in bovine chromaffin cells:
      evidence for a mixed necrotic and apoptotic mechanism with caspases activation.
AB  - Treatment of chromaffin cells with nitric oxide (NO) donors (SNP and SNAP) and
      peroxynitrite produces a time- and dose-dependent necrotic and apoptotic cell
      death. Necrotic cell death was characterized by both an increase in lactate
      dehydrogenase and ATP release and changes in nuclei and cell morphology (as seen
      with fluorescence microscopy analysis with propidium iodide and Hoechst 33342).
      Apoptotic cell death was characterized by nuclear fragmentation and presence of
      apoptotic cell bodies, by a decrease in DNA content, and by an increase in DNA
      fragmentation. Treatment of chromaffin cells with lipopolysaccharide (LPS) or
      cytokines (interferon-gamma, tumor necrosis factor-alpha) resulted only in
      apoptotic cell death. Apoptotic effects of NO-inducing compounds were
      specifically reversed, depending on the stimuli, by the NO scavenger carboxy-PTIO
      (CPTio) or by the NOS inhibitors L-NMA and thiocitrulline. NO-induced apoptotic
      death in chromaffin cells was concomitant to a cell cycle arrest in G0G1 phase
      and a decrease in the number of chromaffin cells in the G2M and S phases of cell
      cycle. All NO-producing compounds were able to induce activation of caspase 3 and
      cytochrome c release, and specific inhibitors of caspase 3 and 9, such as Ac-DEVD
      CHO (CPP32) and Ac-Z-LEHD-FMK, respectively, prevented NO-induced apoptosis in
      chromaffin cells. These results suggest that chromaffin cells could be good
      models for investigating the molecular basis of degeneration in diseases showing
      death of catecholaminergic neurons, phenomenon in which NO plays an important
      role.

PMID- 16625661
TI  - Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-mediated excitotoxic
      axonal damage is attenuated in the absence of myelin proteolipid protein.
AB  - In vivo and in vitro studies have shown that alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)-receptor-mediated excitotoxicity causes
      cytoskeletal damage to axons. AMPA/kainate receptors are present on
      oligodendrocytes and myelin, but currently there is no evidence to suggest that
      axon cylinders contain AMPA receptors. Proteolipid protein (PLP) and DM20 are
      integral membrane proteins expressed by CNS oligodendrocytes and located in
      compact myelin. Humans and mice lacking normal PLP/DM20 develop axonal swellings
      and degeneration, suggesting that local interactions between axons and the
      oligodendrocyte/myelin unit are important for the normal functioning of axons and
      that PLP/DM20 is involved in this process. To determine whether perturbed glial
      axonal interaction affects AMPA-receptor-mediated axonal damage, AMPA (1.5 nmol)
      was injected into the caudate nucleus of anesthetized Plp knockout and wild-type
      male mice (n = 13). Twenty-four hours later, axonal damage was detected by using
      neurofilament 200 (NF 200) immunohistochemistry and neuronal damage detected via
      histology. AMPA-induced axonal damage, assessed with NF 200 immunohistochemistry,
      was significantly reduced in Plp knockout mice compared with wild-type mice (P =
      0.015). There was no significant difference in the levels of neuronal perikaryal
      damage between the Plp knockout and wild-type mice. In addition, there was no
      significant difference in the levels of glutamate receptor subunits GluR1-4 or
      KA2 in Plp knockout compared with wild-type littermates. The present study
      suggests that PLP-mediated interactions among oligodendrocytes, myelin, and axons
      may be involved in AMPA-mediated axonal damage.

PMID- 16625662
TI  - Kainate induces rapid redistribution of the actin cytoskeleton in ameboid
      microglia.
AB  - Microglia are key mediators of the immune response in the central nervous system
      (CNS). They are closely related to macrophages and undergo dramatic morphological
      and functional changes after CNS trauma or excitotoxic lesions. Microglia can be
      directly stimulated by excitatory neurotransmitters and are known to express many
      neurotransmitter receptors. The role of these receptors, however, is not clear.
      This study describes the microglial response to the glutamate receptor agonist
      kainate (KA) and shows via immunochemistry that the alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit GluR1 is
      present on cultured microglia. In the presence of 100 microM or 1 mM KA, cultured
      microglia underwent dramatic morphological and cytoskeletal changes as observed
      by time-lapse photography and quantitative confocal analysis of phalloidin
      labeling. KA-stimulated microglia showed condensation of cytoplasmic actin
      filaments, rapid de- and repolymerization, and cytoplasmic redistribution of
      condensed actin bundles. Rearrangement of actin filaments-thought to be involved
      in locomotion and phagocytosis and to indicate an increased level of activation
      (for reviews see Greenberg [ 1995] Trends Cell Biol. 5:93-99; Imai and Kohsaka [
      2002] Glia 40:164-174)-was significantly increased in treated vs. control
      cultures. Morphological plasticity and membrane ruffling were also seen. These
      findings suggest direct microglial excitation via glutamate receptor pathways.
      Thus, neurotransmitter release after brain or spinal cord injury might directly
      modulate the inflammatory response.

PMID- 16625663
TI  - Biosynthesis of thiamin thiazole: determination of the regiochemistry of the S/O
      acyl shift by using 1,4-dideoxy-D-xylulose-5-phosphate.

PMID- 16625664
TI  - Tetraarylporphyrin as a selective molecular cap for non-Watson-Crick guanine
      adenine base-pair sequences.

PMID- 16625665
TI  - Enhanced DNA vaccine potency by mannosylated lipoplex after intraperitoneal
      administration.
AB  - BACKGROUND: Here we describe a novel DNA vaccine formulation that can enhance
      cytotoxic T lymphocyte (CTL) activity through efficient gene delivery to
      dendritic cells (DCs) by mannose receptor-mediated endocytosis. METHODS:
      Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA
      encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination.
      Mannosylated cationic liposomes (Man-liposomes) were prepared using cholesten-5
      yloxy-N-{4-[(1-imino-2-D-thiomannosylethyl)amino]butyl}formamide (Man-C4-Chol)
      with cationic lipid. The potency of the mannosylated liposome/pCMV-OVA complex
      (Man-lipoplex) was evaluated by measuring OVA mRNA in CD11c+ cells, CTL activity,
      and the OVA-specific anti-tumor effect after in vivo administration. RESULTS: An
      in vitro study using DC2.4 cells demonstrated that Man-liposomes could transfect
      pCMV-OVA more efficiently than cationic liposomes via mannose receptor-mediated
      endocytosis. In vivo studies revealed that the Man-lipoplex exhibited higher OVA
      mRNA expression in CD11c+ cells in the spleen and peritoneal cavity and provided
      a stronger OVA-specific CTL response than intraperitoneal (i.p.) administration
      of the conventional lipoplex and intramuscular (i.m.) administration of naked
      pCMV-OVA, the standard protocol for DNA vaccination. Pre-immunization with the
      Man-lipoplex provided much better OVA-specific anti-tumor effect than naked pCMV
      OVA via the i.m. route. CONCLUSIONS: These results suggested that in vivo active
      targeting of DNA vaccine to DCs with Man-lipoplex might prove useful for the
      rational design of DNA vaccine.

PMID- 16625666
TI  - Hydrothermal chemistry of the copper-triazolate system: A microporous metal
      organic framework constructed from magnetic {Cu3(mu3-OH)(triazolate)3}2+ building
      blocks, and related materials.

PMID- 16625667
TI  - A self-regulatory host in an oscillatory guest motion: complexation of fullerenes
      with a short-spaced cyclic dimer of an organorhodium porphyrin.

PMID- 16625668
TI  - Enantiomerically pure cyclopropenylcarbinols as a source of chiral
      alkylidenecyclopropane derivatives.

PMID- 16625669
TI  - A deep, water-soluble cavitand acts as a phase-transfer catalyst for hydrophobic
      species.

PMID- 16625670
TI  - 1H and 13C NMR study of 5-substituted-4- (arylidene)amino-2,4-dihydro-3H-1,2,4
      triazole-3-thiones and 6-aryl-3-(D-gluco- pentitol-1-yl)-7H-1,2,4-triazolo[3,4-b]
      [1,3,4]thiadiazines.
AB  - Five 5-substituted-4-(arylidene)amino-2,4-dihydro-3H-1, 2,4-triazole-3-thiones
      (2a-2e) and seven 6-aryl-3-(D-gluco-pentitol-1-yl)-7H-1,2,4-triazolo[3,4
      b][1,3,4]thiadiazines (3a-3g) were synthesized. The complete 1H and 13C NMR
      chemical shift assignments were analyzed on one- and two-dimensional NMR
      techniques, including DEPT, NOE-DIF, COSY, gHMBC, and gHSQC.

PMID- 16625671
TI  - Comparison of EQ-5D and SF-6D utilities in mental health patients.
AB  - Various preference-based measures of health are available for use as an outcome
      measure in cost-utility analysis. The aim of this study is to compare two such
      measures EQ-5D and SF-6D in mental health patients. Baseline data from a Dutch
      multi-centre randomised trial of 616 patients with mood and/or anxiety disorders
      were used. Mean and median EQ-5D and SF-6D utilities were compared, both in the
      total sample and between severity subgroups based on quartiles of SCL-90 scores.
      Utilities were expected to decline with increased severity. Both EQ-5D and SF-6D
      utilities differed significantly between patients of adjacent severity groups.
      Mean utilities increased from 0.51 at baseline to 0.68 at 1.5 years follow-up for
      EQ-5D and from 0.58 to 0.70 for SF-6D. For all severity subgroups, the mean
      change in EQ-5D utilities as well as in SF-6D utilities was statistically
      significant. Standardised response means were higher for SF-6D utilities. We
      concluded that both EQ-5D and SF-6D discriminated between severity subgroups and
      captured improvements in health over time. However, the use of EQ-5D resulted in
      larger health gains and consequent lower cost-utility ratios, especially for the
      subgroup with the highest severity of mental health problems.

PMID- 16625672
TI  - Complete assignments of 1H and 13C NMR data for seven arylnaphthalide lignans
      from Justicia procumbens.
AB  - Three new arylnaphthalide lignans named 6'-hydroxy justicidin A (1), 6'-hydroxy
      justicidin B (2) and 6'-hydroxy justicidin C (3) have been isolated from the
      whole plant of Justicia procumbens, together with four known ones, neojusticin A
      (4), chinensinaphthol methyl ester (5), isodiphyllin (6) and taiwanin C (7). The
      complete assignments of 1H and 13C NMR chemical shifts for the new lignans and
      the 13C NMR chemical shifts for the known lignans were obtained for the first
      time by means of 2D NMR techniques, including HSQC and HMBC.

PMID- 16625673
TI  - Helium atom scattering from oxide surfaces.
AB  - Many experimental methods of surface science employ electrons or photons of
      considerable incident energy as probe particles. However, insulating surfaces or
      delicate physisorbed layers may be damaged by these particles and should,
      therefore, be analyzed with a gentler probe: He atom scattering allows to
      determine the symmetry of the unit cell and the detection of phase transitions
      from diffraction measurements as well as the determination of surface and
      adsorbate vibrations by time-of-flight resolved detection. Herein, the
      application of He atom scattering to oxide surfaces is demonstrated on the basis
      of the examples of MgO and ZnO. MgO(001) is a very inert and stable surface,
      whereas hydrogen atoms are chemisorbed on the mixed-terminated ZnO(1010) and on
      both polar faces: ZnO(0001) and ZnO(0001). He atom scattering is very sensitive
      to the presence of hydrogen on surfaces. In addition ZnO reacts with molecules
      such as water, CO and CO(2). It is demonstrated that in combination with
      photoelectron spectroscopy and thermal desorption spectroscopy He atom scattering
      can also contribute to studies of surface chemistry.

PMID- 16625674
TI  - Quantum-dot-labeled DNA probes for fluorescence in situ hybridization (FISH) in
      the microorganism Escherichia coli.
AB  - Semiconductor quantum dots (QDs) as a kind of nonisotopic biological labeling
      material have many unique fluorescent properties relative to conventional organic
      dyes and fluorescent proteins, such as composition- and size-dependent absorption
      and emission, a broad absorption spectrum, photostability, and single-dot
      sensitivity. These properties make them a promising stable and sensitive label,
      which can be used for long-term fluorescent tracking and subcellular location of
      genes and proteins. Here, a simple approach for the construction of QD-labeled
      DNA probes was developed by attaching thiol-ssDNA to QDs via a metal-thiol bond.
      The as-prepared QD-labeled DNA probes had high dispersivity, bioactivity, and
      specificity for hybridization. Based on such a kind of probe with a sequence
      complementary to multiple clone sites in plasmid pUC18, fluorescence in situ
      hybridization of the tiny bacterium Escherichia coli has been realized for the
      first time.

PMID- 16625675
TI  - Adsorption isotherms of ortho- and para-water.

PMID- 16625676
TI  - Atom-molecule interactions on transition metal surfaces: a DFT Study of CO and
      several atoms on Rh(100), Pd(100) and Ir(100).
AB  - Density functional theory (DFT) calculations have been performed to determine the
      interaction energy between a CO probe molecule and all atoms from the first three
      rows of the periodic table coadsorbed on Rh(100), Pd(100) and Ir(100) metal
      surfaces. Varying the coverage of CO or the coadsorbed atom proved to have a
      profound effect on the strength of the interaction energy. The general trend,
      however, is the same in all cases: the interaction energy becomes more repulsive
      when moving towards the right along a row of elements, and reaches a maximum
      somewhere in the middle of a row of elements. The absolute value of the
      interaction energy between an atom-CO pair ranges from about -0.40 eV (39 kJ mol(
      1)) attraction to +0.70 eV (68 kJ mol(-1)) repulsion, depending on the
      coadsorbate, the metal and the coverage. The general trend in interaction
      energies seems to be a common characteristic for several transition metals.

PMID- 16625677
TI  - Luminescence quenching by O2 of a Ru2+ complex attached to zeolite L.

PMID- 16625678
TI  - Enhanced activity and selectivity in cyclohexane autoxidation by inert H-bond
      acceptor catalysts.
AB  - Herein, we demonstrate that the chain-initiating dissociation of cyclohexyl
      hydroperoxide, CyOOH, is substantially accelerated by H-bond acceptors (e.g.
      Teflon), which assist O-O bond breaking by stabilising the leaving *OH radical.
      This is a completely new approach to boost the chain-propagating radical
      concentration. Indeed, up to now, literature has remained focussed on transition
      metal catalysis. In addition to this initiation effect, we demonstrate how inert
      perfluorinated compounds are also able to steer the selectivity at the molecular
      level, by promoting the conversion of the intermediate cyclohexyl hydroperoxide
      to the most desired end-product, cyclohexanone. This effect is explained by an
      enhanced, H-bond-assisted, hydroperoxide propagation. This hitherto overlooked
      hydroperoxide propagation was recently presented by us as the dominant
      cyclohexanone and cyclohexanol source. We herein thus confirm our previously
      reported autoxidation scheme, and illustrate its usefulness as a solid basis for
      designing new catalytic systems.

PMID- 16625679
TI  - Uncalibrated modelling of conservative tracer and pesticide leaching to
      groundwater: comparison of potential Tier II exposure assessment models.
AB  - The Root Zone Water Quality Model (RZWQM) and Pesticide Root Zone Model (PRZM)
      are currently being considered by the Office of Pesticide Programs (OPP) in the
      United States Environmental Protection Agency (US EPA) for Tier II screening of
      pesticide leaching to groundwater (November 2005). The objective of the present
      research was to compare RZWQM and PRZM based on observed conservative tracer and
      pesticide pore water and soil concentrations collected in two unique groundwater
      leaching studies in North Carolina and Georgia. These two sites had been used
      previously by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA)
      Environmental Model Validation Task Force (EMVTF) in the validation of PRZM. As
      in the FIFRA EMVTF PRZM validation, 'cold' modelling using input parameters based
      on EPA guidelines/databases and 'site-specific' modelling using field-measured
      soil and hydraulic parameters were performed with a recently released version of
      RZWQM called RZWQM-NAWQA (National Water Quality Assessment). Model calibration
      was not performed for either the 'cold' or 'site-specific' modelling. The models
      were compared based on predicted pore water and soil concentrations of bromide
      and pesticides throughout the soil profile. Both models tended to predict faster
      movement through the soil profile than observed. Based on a quantitative
      normalised objective function (NOF), RZWQM-NAWQA generally outperformed or was
      equivalent to PRZM in simulating pore water and soil concentrations. Both models
      were more successful in predicting soil concentrations (i.e. NOF < 1.0 for site
      specific data, which satisfies site-specific applicability) than they were at
      predicting pore water concentrations.

PMID- 16625680
TI  - Plant-derived natural products exhibiting activity against formosan subterranean
      termites (Coptotermes formosanus).
AB  - The Formosan subterranean termite, Coptotermes formosanus Shiraki, is among the
      most devastating termite pests. Natural products derived from plant extracts were
      tested in a discovery programme for effective, environmentally friendly termite
      control agents. Among the natural products tested, vulgarone B (isolated from
      Artemisia douglasiana Besser), apiol (isolated from Ligusticum hultenii (Fern.)
      Calder & Taylor) and cnicin (isolated from Centaurea maculosa Lam.) exhibited
      significantly higher mortalities than in untreated controls in laboratory
      bioassay. These compounds are present at high levels in their respective plant
      sources and also possess other biological activities such as phytotoxic and
      antifungal properties.

PMID- 16625681
TI  - The epimerization of peptide aldehydes--a systematic study.
AB  - Peptide aldehydes are interesting targets as enzyme inhibitors, and can be used
      for pseudopeptide chemistry or ligation. However, they are known to be subjected
      to epimerization during synthesis or purification. By (1)H NMR, a model dipeptide
      aldehyde can be used to check the possible epimerization occurring during
      synthesis. Various purification methods were investigated, but none was free from
      epimerization.

PMID- 16625682
TI  - Design and synthesis of potent, highly selective vasopressin hypotensive
      agonists.
AB  - We report here the solid-phase synthesis and vasodepressor potencies of a new
      lead vasopressin (VP) hypotensive peptide [1(beta-mercapto-beta,beta
      pentamethylenepropionic acid)-2-0-ethyl-D-tyrosine, 3-arginine, 4-valine, 7
      lysine, 9-ethylenediamine] lysine vasopressin, d(CH(2))(5)[D-Tyr(Et)(2), Arg(3),
      Val(4), Lys(7), Eda(9)]LVP (C) and 21 analogues of C with single modifications at
      positions 9 (1-13), 6 (14), 2 (16-20) and combined modifications at positions 6
      and 10 (15) and 2 and 10 (21). Peptides 1-13 have the following replacements for
      the Eda residue at position 9 in C: (1) Gly-NH(2); (2) Gly-NH-CH(3); (3) Ala
      NH(2); (4) Ala-NH-CH(3), (5) Val-NH(2); (6) Cha-NH(2); (7) Thr-NH(2); (8) Phe
      NH(2); (9) Tyr-NH(2); (10) Orn-NH(2); (11) Lys-NH(2); (12) D-Lys-NH(2); (13) Arg
      NH(2). Peptide 14 has the Cys residue at position 6 replaced by Pen. Peptide 15
      is the retro-Tyr(10) analogue of peptide 14. Peptides 16-20 have the D-Tyr(Et)
      residue at position 2 in C replaced by the following substituents: D-Trp (16); D
      2-Nal (17); D-Tyr(Bu(t))(18); D-Tyr(Pr(n)) (19); D-Tyr(Pr(i)) (20). Peptide 21 is
      the retro-Tyr(10) analogue of peptide 20. C and peptides 1-21 were evaluated for
      agonistic and antagonistic activities in in vivo vasopressor (V(1a)-receptor),
      antidiuretic (V(2)-receptor), and in in vitro (no Mg(2+)) oxytocic (OT-receptor)
      assays in the rat, and, like the original hypotensive peptide, d(CH(2))(5)[D
      Tyr(Et)(2), Arg(3), Val(4)]AVP (A) (Manning et al., J. Peptide Science 1999,
      5:472-490), were found to exhibit no or negligible activities in these assays.
      Vasodepressor potencies were determined in anesthetized male rats with baseline
      mean arterial blood pressure (BP) maintained at 100-120 mmHg. The effective dose
      (ED), in microg/100 g i.v., the dose required to produce a vasodepressor response
      of 5 cm(2) area under the vasodepressor response curve (AUC) during the 5-min
      period following the injection of the test peptide, was determined. The EDs
      measure the vasodepressor potencies of the hypotensive peptides C and 1-21
      relative to that of A (ED = 4.66 microg/100 g) and to each other. The following
      ED values in microg/100 g were obtained for C and for peptides 1-21; C 0.53; (1)
      2.41; (2) 1.13; (3) 1.62; (4) 0.80; (5) 1.83; (6) 1.56; (7) 2.12, (8) 2.58; (9)
      1.40; (10) 0.88; (11) 0.90; (12) 0.85; (13) 0.68; (14) 0.99; (15) 1.05; (16)
      0.66; (17) 0.54; (18) 0.33; (19) 0.18; (20) 0.15; (21) 0.14. All of the
      hypotensive peptides reported here are more potent than A. Peptides 20 and 21
      exhibit a striking 30-fold enhancement in vasodepressor potencies relative to A.
      With a vasodepressor ED = 0.14, peptide 21 is the most potent VP vasodepressor
      agonist reported to date. Because it contains a retro-Tyr(10) residue, it is a
      promising new radioiodinatable ligand for the putative VP vasodilating receptor.
      Some of these new hypotensive peptides may be of value as research tools for
      studies on the complex cardiovascular actions of VP and may lead to the
      development of a new class of antihypertensive agents.

PMID- 16625683
TI  - Rapid bidirectional allele-specific PCR identification for triazine resistance in
      higher plants.
AB  - Triazine resistance is reported to be due to chloroplast herbicide target
      insensitivity in most species, and this is most often caused by a Ser(264)-Gly
      mutation at the D1 protein. In order to ascertain whether this mutation is really
      predominant amongst resistant plants, and also for gene flow studies, a rapid
      test is needed that allows the testing of large quantities of plants. Here a
      bidirectional allele-specific PCR (polymerase chain reaction) identification is
      proposed. The designed primers were shown to be universal in the three grass and
      three broadleaf species examined.

PMID- 16625684
TI  - Design of a minimized cyclic tetrapeptide that neutralizes bacterial endotoxins.
AB  - Septic shock is a leading cause of mortality in intensive care patients, and no
      specific drugs are as yet available for its treatment. Therefore, new leads are
      required in order to increase the number of active molecules that may develop
      into efficacious and safe LPS-neutralizing molecules during pre-clinical stages.
      We used peptides, derived from the binding regions of known LPS-binding proteins,
      as scaffolds to introduce modifications at the amino acid level. Structure
      activity relationship studies have shown that these modifications generate highly
      active peptides. Thus, from a bioactive peptide with an initial 16 amino acid
      residues, a tetrapeptide sequence was determined. After inserting this sequence
      in a Cys cyclic peptide, it showed the same biological activity as the parent
      peptide. This sequence could provide the basis for the design of small molecules
      with LPS-binding properties.

PMID- 16625685
TI  - Five-Year Report of Croatian Medical Journal's Research Integrity Editor -
      Policy, Policing, or Policing Policy.

PMID- 16625686
TI  - Doing well or doing good?

PMID- 16625687
TI  - Effect of head position on cerebrospinal fluid pressure in cats: comparison with
      artificial model.
AB  - AIM: To demonstrate that changes in the cerebrospinal fluid (CSF) pressure in the
      cranial cavity and spinal canal after head elevation from the horizontal level
      occur primarily due to the biophysical characteristics of the CSF system, ie,
      distensibility of the spinal dura. METHODS: Experiments in vivo were performed on
      cats and a new artificial model of the CSF system with dimensions similar to the
      CSF system in cats, consisting of non-distensible cranial and distensible spinal
      part. Measurements of the CSF pressure in the cranial and spinal spaces were
      performed in chloralose-anesthetized cats (n = 10) in the horizontal position on
      the base of a stereotaxic apparatus (reference zero point) and in the position in
      which the head was elevated to 5 cm and 10 cm above that horizontal position.
      Changes in the CSF pressure in the cranial and spinal part of the model were
      measured in the cranial part positioned in the same way as the head in cats (n =
      5). RESULTS: When the cat was in the horizontal position, the values of the CSF
      pressure in the cranial (11.9 +/- 1.1 cm H2O) and spinal (11.8 +/- 0.6 cm H2O)
      space were not significantly different. When the head was elevated 5 cm or 10 cm
      above the reference zero point, the CSF pressure in the cranium significantly
      decreased to 7.7 +/- 0.6 cm H2O and 4.7 +/- 0.7 cm H2O, respectively, while the
      CSF pressure in the spinal space significantly increased to 13.8 +/- 0.7 cm H2O
      and 18.5 +/- 1.6 cm H2O, respectively (P<0.001 for both). When the artificial CSF
      model was positioned in the horizontal level and its cranial part elevated by 5
      cm and 10 cm, the changes in the pressure were the same as those in the cats when
      in the same hydrostatic position. CONCLUSIONS: The new model of the CSF system
      used in our study faithfully mimicked the changes in the CSF pressure in cats
      during head elevation in relation to the body. Changes in the pressure in the
      model were not accompanied by the changes in fluid volume in the non-distensible
      cranial part of the model. Thus, it seems that the changes in the CSF pressure
      occur due to the biophysical characteristics of the CSF system rather than the
      displacement of the blood and CSF volumes from the cranium to the lower part of
      body.

PMID- 16625688
TI  - Anterior instrumentation for correction of adolescent thoracic idiopathic
      scoliosis: historic prospective study.
AB  - AIM: To compare the results of anterior instrumentation and standard posterior
      procedure for correction of adolescent thoracic idiopathic scoliosis. METHODS:
      The study included 50 patients with adolescent thoracic idiopathic scoliosis who
      underwent corrective spinal surgery. Anterior spinal fusion by use of modified
      Zielke ventral derotation system (anterior approach to spine through thorax) was
      performed in 25 patients, whereas posterior approach was used in 25 patients. The
      average preoperative thoracic curve in coronal plane was 66.7 +/- 9.9 degrees and
      65.0 +/- 11.7 degrees in the anterior and posterior correction groups,
      respectively. The median age of patients before surgery was 14 years (range, 12
      18) in the anterior and 16 years (range, 13-18) in the posterior correction
      group. Women-to-men ratio was 22 to 3 in each group. Coronal and sagittal
      correction, apical vertebral body rotation, rib hump, and rib depression
      correction were measured before surgery and at the first (30 days after surgery)
      and at the second follow-up visit (at least 2 years after surgery).
      Posteroanterior and laterolateral radiographs of the erect spine were used
      (according to the method of Cobb and Nash-Moe) to assess coronal, sagittal, and
      horizontal plane corrections. Rib hump and rib depression were measured with
      Thulbourne-Gillespie measuring device. The differences in scoliosis correction
      parameters in the two groups were tested with Student two-tailed t test. RESULTS:
      In the coronal plane, the thoracic curve of 66.7 +/- 9.9 degrees before surgery
      in the anterior correction group was reduced to 14.8 +/- 8.7 degrees after
      surgery (78.1 +/- 12.4% relative correction), and the curve of 65.0 +/- 11.7
      degrees in the posterior correction group was corrected to 29.2 +/- 7.8 degrees
      after surgery (55.1 +/- 8.6% relative correction) (P<0.001). Apical vertebral
      body rotation correction according to the Nash-Moe classification from 2.0 +/-
      0.4 degrees to 0.8 +/- 0.6 degrees was achieved in the anterior correction group
      (62.0 +/- 26.6% relative correction) and from 1.7 +/- 0.5 degrees to 1.4 +/- 0.5
      degrees in the posterior correction group (12.0 +/- 21.8% relative correction)
      (P<0.001). Rib hump correction from 22.4 +/- 15.5 mm to 5.4 +/- 5.2 mm was found
      in the anterior correction group (70.9 +/- 26.0% relative correction) and from
      25.3 +/- 7.0 mm to 13.6 +/- 6.8 mm (48.4 +/- 16.5% relative correction) in the
      posterior correction group (P = 0.084). CONCLUSION: Compared with the standard
      posterior approach, the anterior approach resulted in better three-dimensional
      correction of idiopathic thoracic scoliosis.

PMID- 16625689
TI  - Intracranial pressure and biochemical indicators of brain damage: follow-up
      study.
AB  - AIM: To investigate the relation between metabolic parameters of the brain
      tissue, as direct indicators of real metabolic conditions within the brain, and
      intracranial pressure, as the consequence of pathophysiological changes. METHODS:
      Twelve patients with closed head injuries were followed up for 24 hours after
      injury. A Codman parenchymal intracranial pressure and a Neurotrend electrode
      were inserted within 3 hours after injury to monitor parenchymal intracranial
      pressure, brain tissue partial oxygen pressure (P(br)O2), brain tissue partial
      carbon dioxide pressure (P(br)CO2), pH, and brain tissue temperature. Data
      detected at 8-hourly intervals were compared with repeated measures analysis of
      variance. RESULT: At the initial observation, the mean value of intracranial
      pressure was 22.2 +/- 3.2 mm Hg. Although it increased at the second and
      decreased at the third measurement, the differences between the measurements were
      not significant (P = 0.320). The value of P(br)CO2 was increased from the
      beginning (63.3 +/- 6.0 mm Hg), whereas P(br)O2 was within the normal range at
      the first measurement (38.9 +/- 6.9 mm Hg), but significantly decreased after 8
      hours (P = 0.004), remaining low at later time points. CONCLUSION: After brain
      injury, changes in P(br)CO2 are visible earlier than those in P(br)O2.
      Improvement in intracranial pressure values did not necessary mean improvement in
      the brain tissue oxygenation. In addition to intracranial pressure, P(br)O2,
      P(br)CO2 and pH should also be monitored, as they directly reflect the real
      metabolic conditions within brain tissue and may be used in predictions about the
      outcome and possible therapeutic approaches.

PMID- 16625691
TI  - Bladder and bowel control in children with cerebral palsy: case-control study.
AB  - AIM: To determine the age of development of bladder and bowel control and the
      frequency of enuresis, encopresis, and urinary infections in children with
      cerebral palsy. METHODS: The study included 45 children with cerebral palsy who
      regularly attended a rehabilitation center in Isparta, Turkey, and two groups of
      age- and sex-matched children, 37 siblings of the children with cerebral palsy
      and 37 healthy children. Demographic data and information on the age of
      development of total bladder and bowel control and presence of possible urinary
      symptoms in children were collected from their caregivers by use of a
      questionnaire. Frequency of enuresis and encopresis was estimated among the
      children aged > or =5 years. A mid-way urinary sample was obtained from 40, 22,
      and 21 children in the cerebral palsy, siblings, and healthy children,
      respectively. RESULTS: The mean age of nighttime bladder and bowel control
      development was 47 months (95% confidence interval [CI], 35-58) and 45 (36-55)
      months, respectively, for the children with cerebral palsy, 35 months (95% CI, 24
      46) and 26 months (95% CI, 24-28), respectively, for their siblings, and 27
      months (95% CI, 22-33) and 25 months (95% CI, 23-27) months, respectively, for
      the healthy children. Among the children aged > or =5 years, enuresis was present
      in 11 of 34 children with cerebral palsy, 7 of 30 siblings, and 4 of 30 healthy
      children (P = 0.200), whereas encopresis was present in 5 children with cerebral
      palsy, one sibling, and one healthy child. Constipation was significantly more
      present in chidlren with cerebral palsy than in other two groups (P<0.001). Urine
      culture was positive in 13 children with cerebral palsy, 1 sibling, and 2 healthy
      chidlren (P = 0.024). There were no significant differences in other urinary
      symptoms and laboratory findings among the three groups. CONCLUSION: The children
      with cerebral palsy gained bladder and bowel control at older age in comparison
      with their siblings and healthy children. They also had more frequent enuresis
      and urinary infections.

PMID- 16625690
TI  - Long-term cognitive deficits in patients with good outcomes after aneurysmal
      subarachnoid hemorrhage from anterior communicating artery.
AB  - AIM: To evaluate long-term cognitive consequences of subarachnoid hemorrhage with
      good outcome and the opinion of patients and their relatives about these
      consequences. METHODS: The study included 10 patients surgically treated for
      subarachnoid hemorrhage due to the rupture of aneurysm of the anterior
      communicating artery 2 or more years earlier, and 10 age- and sex-matched healthy
      controls. The preoperative and postoperative course in the patients was
      uneventful. Clinical and psychosocial factors and cognitive status of the
      patients were assessed by use of checklists and neuropsychological tests for
      executive functions, attention, and memory, and event-related potential
      recordings (waves P3a and P3b) with tree-stimulus auditory oddball paradigm,
      which was also performed in healthy controls. RESULTS: The number of reported
      cognitive problems negatively correlated with the patients' level of community
      integration (rho range, -0.22 to -0.75). The average neuropsychological results
      ranged between the 12th and 46th percentile. Impaired results were found in 7
      patients across different tests and were most frequent for visual memory,
      followed by verbal memory and executive functions. A clear decline in cognitive
      functioning was observed in 3 patients. Neither P3a nor P3b wave could be found
      in 3 patients. In comparison with controls, patients had significantly longer P3b
      wave latencies (364 vs 334 ms; Mann-Whitney U test, P = 0.025). We found
      statistically non-significant, but still prominent negative correlations between
      the sustained attention results and latencies of P3a (rho = -0.58; P = 0.172) and
      P3b (rho = -0.58; P = 0.172) waves. CONCLUSION: Despite good outcome after
      subarachnoid hemorrhage, persistent cognitive consequences were still manifest,
      limiting the patients' psychosocial functioning. The correlation between
      neuropsychological and neurophysiological measures indicated frontal lobe damage,
      which in some patients persisted for years after the hemorrhage.

PMID- 16625692
TI  - Microcoagulation of junctional dorsal root entry zone is effective treatment of
      brachial plexus avulsion pain: long-term follow-up study.
AB  - AIM: To analyze long-term clinical results of coagulation lesions of the dorsal
      root entry zone (DREZ) in patients with deafferentation pain due to brachial
      plexus avulsion and to correlate the pain relief after DREZ coagulation with pain
      duration before the DREZ coagulation. METHODS: Twenty-six patients with
      intractable deafferentation pain after brachial plexus avulsion lesion were
      treated for pain at the Department of Neurosurgery. Junctional coagulation lesion
      was made with bipolar forceps along the DREZ. The patients assessed post
      operative analgesic effect using a visual analog scale at 1 week, 1 year, 3
      years, and 5 years after the surgery. RESULTS: The greatest pain relief was
      reported immediately after the DREZ procedure. Over the 5-year follow-up period,
      the pain relief effect gradually and significantly decreased. There were no
      significant differences between the pain relief evaluated at 1 week and after 1
      year and between the pain relief evaluated at 1 week and after 3 years. There was
      a correlation between the pain duration before the surgery and pain relief after
      the surgery, with best correlation found between pain duration before surgery and
      pain relief 5 years after DREZ procedure (r = 0.623, P = 0.007). CONCLUSION: The
      long-term follow up showed that the pain relief gradually decreased over 5 years
      after surgery. However, the pain relief still did not significantly decrease
      after 3 years.

PMID- 16625693
TI  - Somatosensory evoked potentials in children with brain ventricular dilatation.
AB  - AIM: To determine possible nerve conduction changes in the somatosensory pathway
      in children with brain ventricular dilatation and to estimate the relation
      between the ventricular size and somatosensory evoked potentials (SEP). METHODS:
      Twelve children with ventricular dilatation (frontal and occipital horn ratios
      >0.44) and 19 children without ventricular dilatation (control group), aged
      between 2 and 15 years, were included in the study. Somatosensory evoked
      responses to median nerve stimulation were recorded in both groups. Evoked
      potentials were recorded by silver/silver chloride cup electrodes from Erb's
      point in the supraclavicular fossa (wave N9), the cervical spine at the C7
      vertebral prominence (wave N13), and the scalp above the contralateral sensory
      cortex at the point C3' or C4', 1 cm behind the C3 or C4 site in the standard 10
      20 system (wave N19). Computed tomography scanning was performed to estimate
      ventricular dilatation. RESULTS: The conduction time of the central somatosensory
      pathway (N19-N13 interwave latency) was significantly longer in the children with
      ventricular dilatation than in the control group (P = 0.046). A statistically
      significant but weak correlation was found between the frontal and occipital horn
      ratio values and the N19-N13 interwave latencies in the subjects with enlarged
      ventricles (r = 0.579, P = 0.045). CONCLUSION: Ventricular dilatation is
      associated with prolonged conduction of the central part of the somatosensory
      pathway in children. Early detection and treatment of hydrocephalus could be
      useful in preventing long-term consequences of high intraventricular pressure.

PMID- 16625694
TI  - Amplitude-integrated electroencephalography in full-term newborns without severe
      hypoxic-ischemic encephalopathy: case series.
AB  - AIM: To assess the diagnostic value of amplitude-integrated
      electroencephalography (EEG) in comparison to standard EEG in newborns without
      severe hypoxic-ischemic encephalopathy who were at risk for seizures. METHODS:
      The study included a consecutive series of 18 term newborns without severe
      hypoxic-ischemic encephalopathy, but with clinical signs suspicious of epileptic
      seizures, history of loss of social contact, disturbance of muscle tone,
      hyperirritability, and/or jitteriness. Amplitude-integrated and standard EEG
      tracings were assessed for background pattern, epileptiform activity, and sleep
      wake cycling. RESULTS: Amplitude-integrated EEG and standard EEG recordings of 15
      newborns were suitable for analysis. Only two different background patterns were
      seen on amplitude-integrated EEG and standard EEG, with the absence of severely
      abnormal background patterns. Of 15 newborns, epileptiform discharges were
      present on amplitude-integrated EEG in 3 newborns, and on standard EEG in 6
      newborns. Sensitivity of seizures discharges on amplitude-integrated EEG to
      correspond with epileptiform discharges on standard EEG was 50%; specificity
      100%,positive predictive value 100%, and negative predictive value 75%. Of 4
      newborns suspected of having sleep myoclonus, amplitude-integrated EEG correctly
      identified the newborn who had epileptiform activity on standard EEG. CONCLUSION:
      The diagnostic value of amplitude-integrated EEG monitoring of term newborns
      without severe hypoxic-ischemic encephalopathy is limited, but could have a role
      in evaluating presence or absence of epileptiform activity and in differentiating
      non-epileptic movement from seizures.

PMID- 16625695
TI  - Laser-Doppler flowmetry and Horner's syndrome in patients with complete
      unilateral damage to the parasellar sympathetic fibers during cavernous sinus
      surgery.
AB  - AIM: To determine ocular, sudomotor, and vasomotor components of Horner's
      syndrome resulting from complete unilateral intraoperative damage to the
      parasellar sympathetic fibers during cavernous sinus surgery. METHODS: Complete
      damage to the parasellar sympathetic fibers was found in four patients operated
      for central skull base lesions. Pupilometry, eyelid fissure measurement, Hertel's
      exophthalmometry, starch iodine sweat test, and laser-Doppler perfusion
      assessment of bilaterally symmetrical forehead and cheek areas were performed.
      RESULTS: Pupil diameter was smaller and the eyelid fissure was >2 mm narrower on
      the affected side in all four patients. Exophthalmometry after the operation
      never revealed >1 mm difference. Anhydrosis was localized to the medial forehead
      in three and to the entire forehead in one patient. Average perfusion did not
      significantly differ between the affected and opposite side of the forehead or
      cheek. CONCLUSIONS: The parasellar sympathetic fibers exclusively innervate the
      orbit and variably innervate the forehead sweat glands. No conclusion regarding
      their contribution to the facial vasomotor control could be established.

PMID- 16625696
TI  - H wave and spinal root potentials in neuromonitoring of S1 root function during
      evacuation of herniated disc: preliminary results.
AB  - AIM: To determine the changes in the tibial H reflex and spinal nerve root
      potentials (SRPs) of the S1 root during posterior discectomy and the effects of
      surgical manipulation. METHODS: Tibial H reflex responses (M and H waves) were
      intermittently recorded from the soleus muscle by surface electrodes during
      different stages of surgery in 5 patients with S1 radiculopathy. All patients had
      Achilles reflex preserved bilateraly and no paresis on manual strength testing
      preoperatively. SRPs were additionally obtained by direct epidural recordings
      from the surgically exposed S1 root in 2 of them. RESULTS: The variations in the
      amplitude of H wave were minor and reversible upon the cessation of surgical
      manipulation of the root, but the H reflex was not lost either temporarily or
      permanently in any of the patients. Prolongation of H wave latency by up to 18%
      at the end of surgery in comparison with preoperative value was noticed in 4
      patients. However, there was increased degree of desynchronization of the SRP in
      some phases of the spinal root manipulation, such as root mobilization before the
      disc incision and retraction during the disc evacuation. H waves and SRPs were
      continuously present during the surgery. Ankle jerks were preserved
      postoperatively in all 5 patients. CONCLUSION: Unremarkable variations in H wave
      latency may be followed by increased SRP desynchronization. Monitoring of the
      epidurally recorded SRPs seems to be more sensitive to surgical manipulations of
      the spinal nerve root than the tibial H reflex recordings from the soleus muscle.

PMID- 16625697
TI  - Long-lasting partial regression of glioblastoma multiforme achieved by
      edotecarin: case report.
AB  - We describe the response to a new chemotherapy agent, topoisomerase I inhibitor
      edotecarin in an 18-year-old woman with recurring glioblastoma. The therapy was
      administered for 17 months. The radiological partial response and clinical
      improvement have been achieved, with minor toxicity. Median survival of patients
      with glioblastoma is 10 months. With edotecarin we have achieved promising
      result, which should encourage further investigations to develop more efficient
      therapy for such a deadly disease.

PMID- 16625698
TI  - Sellar region surgery in Croatia in the first half of 20th century.
AB  - We reconstructed the historical development of surgical approaches to the
      pituitary gland, which were used in Croatia in the first half of the 20th
      century, on the basis of earliest clinical case reports and descriptions of
      initial surgical attempts. The first published case report on surgical treatment
      of acromegaly was described, as well as the review of 11 patients with pituitary
      disease admitted to the Ophthalmology Clinic in Zagreb in the period 1925-1927.
      The earliest 5 reports on pituitary surgery dating from 1925 were analyzed to
      reveal the circumstances that led to the development of transsphenoidal approach
      as a method of choice in Croatia, when this technique was becoming obsolete in
      other parts of the world. Frequent modifications of surgical approaches to sellar
      region have been shown a suitable historical-medical model for analysis of
      changes in surgical trends.

PMID- 16625699
TI  - Prevalence of CCR5 Gene 32-Basepair Deletion in Populations of Slavic Origin.

PMID- 16625700
TI  - Alterations in intestinal contractility during inflammation are caused by both
      smooth muscle damage and specific receptor-mediated mechanisms.
AB  - AIM: To evaluate motoric intestinal disturbances during inflammation with
      Trichinella spiralis in rats as an experimental model. METHODS: We examined the
      changes in worm-positive (jejunum) and worm-free (ileum) intestinal segments of
      rats infected with T. spiralis. To investigate the relationship between
      structural and functional changes in smooth muscle, we measured the thickness of
      the muscle layers of rat jejunum and ileum. Mechanical responses to KCl 30
      mmol/L, acetylcholine (ACh) 10(-8)-10(-4) mol/L, substance P (SP) 10(-9)-10(-5)
      mol/L, and to electrical field stimulation of longitudinal muscle strips in the
      jejunum and ileum were studied in muscle bath as controls (day 0) and on day 2,
      6, 14, 23, and 72 after infection. RESULTS: After T. spiralis infestation, an
      inflammation of the mucosal and submucosal layers of jejunum was observed,
      whereas in the worm-free ileum there was not any inflammatory infiltrate.
      Increase in the smooth muscle thickness of both jejunum and ileum were correlated
      with increased responses to depolarizing agent KCl and to ACh. However, responses
      to SP were decreased on day 14-23 after infection in jejunum and from day 6-14
      after infection in ileum. Electric field stimulation-induced contractions were
      transiently decreased in the jejunum (day 2 after infection) but in the ileum the
      contractile responses were decreased until the end of the study period.
      CONCLUSIONS: Alterations in intestinal smooth muscle function do not require the
      presence of the parasite and the absence of histopathological signs of
      inflammation do not warrant intact motor function. Changes in motor responses
      after T. spiralis infection are not only due to smooth muscle damage but also to
      disturbances in specific receptor-mediated mechanisms.

PMID- 16625701
TI  - Peripheral arterial disease and ankle-brachial pressure index as predictors of
      mortality in residents of Metlika County, Slovenia.
AB  - AIM: To test how the presence of peripheral arterial disease predicted mortality
      of middle-aged and elderly residents of Metlika county, a rural area in
      southeastern Slovenia. METHODS: In 1987, we interviewed and examined a
      representative cohort of 646 subjects aged 45-80 years at inclusion without overt
      coronary or cerebrovascular disease, for cardiovascular risk factors and measured
      the ankle-brachial pressure index (ABPI). Peripheral arterial disease was defined
      as ABPI<0.90. The subjects were followed up 15 years or until death. All-cause
      mortality and cardiovascular mortality were assessed and compared between
      subjects with and without peripheral arterial disease in a multivariate model.
      RESULTS: There were 580 subjects with normal ABPI and 66 subjects with peripheral
      arterial disease, among which 49 were asymptomatic and 17 had intermittent
      claudication. Because subjects with peripheral arterial disease were on average
      10 years older than those without peripheral arterial disease, the mere presence
      of peripheral arterial disease was not an independent predictor of mortality.
      However, there was a significant interaction of peripheral arterial disease with
      age, with a more pronounced adverse prognostic effect of peripheral arterial
      disease in younger than in older age groups. For a 55-year-old subject with
      peripheral arterial disease, the hazard ratio of dying from any cause in the
      follow-up period was 2.44 (95% confidence interval [CI], 1.15-4.96) in comparison
      to an age-matched subject without peripheral arterial disease, but at 75 years of
      age, the hazard ratio decreased to only 0.71 (95% CI, 0.46-1.09). For
      cardiovascular mortality, the hazard ratio in the presence of peripheral arterial
      disease was 6.05 (95% CI, 1.87-16.27) at 55 years and 0.92 (95% CI, 0.54-1.52) at
      75 years. Among patients with peripheral arterial disease, each decrement of ABPI
      at inclusion by 0.10 significantly increased the cardiovascular mortality after
      15 years by 30% (P = 0.038). CONCLUSION: Peripheral arterial disease, even
      asymptomatic, is an important predictor of adverse cardiovascular prognosis in
      relatively young patients. Reduced ABPI is a strong, independent predictor of
      cardiovascular mortality in all patients with peripheral arterial disease.

PMID- 16625702
TI  - Health behavior among Lithuania's adolescents in context of European Union.
AB  - AIM: To compare health behavior patterns of adolescents in Lithuania with health
      behavior of adolescents in European Union (EU) in 2001/2002. METHODS: The study
      was carried out in conformity with the methodology of Health Behavior in School
      aged Children: a World Health Organization cross-national study. Three country
      representative samples of schoolchildren, aged 11, 13, and 15, were surveyed in
      25 EU countries and regions in 2001/2002 school year. The study instrument was a
      standardized questionnaire that included questions on alcohol consumption,
      smoking, illegal drugs use, physical activity, and other patterns of health
      behavior. The rate or mean values of the targeted health behavior of Lithuanian
      students were assessed and compared to those calculated as an average for the EU
      countries and regions. RESULTS: We found an early onset of alcohol consumption
      among Lithuanian boys. Lithuanian boys and girls across all age groups reported
      being drunk two and more times more often than their peers from other EU member
      states. Lithuanian 15-year-old boys smoked more often that did their European
      peers, while girls smoke more rarely. The prevalence of drugs (marihuana group)
      use among Lithuanian students is relatively low: the prevalence of drug use among
      15-year-olds in Lithuania is two times lower than the prevalence in other EU
      countries and regions (11.2% vs 24.5% for boys and 4.5% vs 18.3% for girls,
      respectively). Physical activity of Lithuanian adolescents is rather high in
      comparison with their EU peers, although many students watch television for > or
      =4 hours a day. Lithuanian students did not eat sweets often, or drank soft
      drinks (Coca Cola and other), and they ate fruits and had breakfast every school
      day. With respect to hygienic habits, approximately only one in 3 boys and every
      second girl brushed their teeth more than once a day. CONCLUSIONS: There are
      health behavior differences between adolescents in Lithuania and those in other
      EU countries. The disparities among health behavior of young people in EU
      countries and regions require Lithuanian and EU health policy to develop
      initiatives aimed at decreasing health behavior inequalities.

PMID- 16625704
TI  - The three aspects of malady.

PMID- 16625703
TI  - Attitudes of Roma toward smoking: qualitative study in Slovenia.
AB  - AIM: To understand the reasons for widespread smoking behavior among Roma in
      Slovenia for the purpose of developing successful smoking cessation
      interventions. METHOD: A qualitative focus group approach using a combination of
      pre-structured and open-ended questions was applied to collect the data from the
      representative members of the Roma community in southern Slovenia. The
      discussions were audiotaped and transcribed, and the collected data analyzed
      according to qualitative content analysis theory. RESULTS: The content analysis
      revealed that smoking was a strong part of the cultural, ethnic, and individual
      identity of the Roma. Even children smoked. Doctor's advice to quit smoking was
      usually not followed and the attempts to quit were usually unsuccessful.
      Difficult financial situation was never mentioned as a possible motive to quit.
      Roma held a tenacious belief that the harmful effects of smoking were in the
      hands of destiny and did not associate the smoking-related illness with the
      habit. CONCLUSIONS: Traditional strategies for smoking cessation are largely
      ineffective among the Roma because of their different attitudes toward smoking.
      Therefore, innovative and culturally acceptable methods need to be developed.

PMID- 16625705
TI  - Who accesses antiretroviral drugs within public sector in Malawi?

PMID- 16625707
TI  - Training children to save heart attack victims.

PMID- 16625706
TI  - Proteomic technology for biomarker profiling in cancer: an update.
AB  - The progress in the understanding of cancer progression and early detection has
      been slow and frustrating due to the complex multifactorial nature and
      heterogeneity of the cancer syndrome. To date, no effective treatment is
      available for advanced cancers, which remain a major cause of morbidity and
      mortality. Clearly, there is urgent need to unravel novel biomarkers for early
      detection. Most of the functional information of the cancer-associated genes
      resides in the proteome. The later is an exceptionally complex biological system
      involving several proteins that function through posttranslational modifications
      and dynamic intermolecular collisions with partners. These protein complexes can
      be regulated by signals emanating from cancer cells, their surrounding tissue
      microenvironment, and/or from the host. Some proteins are secreted and/or cleaved
      into the extracellular milieu and may represent valuable serum biomarkers for
      diagnosis purpose. It is estimated that the cancer proteome may include over 1.5
      million proteins as a result of posttranslational processing and modifications.
      Such complexity clearly highlights the need for ultra-high resolution proteomic
      technology for robust quantitative protein measurements and data acquisition.
      This review is to update the current research efforts in high-resolution
      proteomic technology for discovery and monitoring cancer biomarkers.

PMID- 16625708
TI  - Demystifying small RNA pathways.

PMID- 16625709
TI  - Occurrence of methicillin-resistant Staphylococcus aureus strains from cattle and
      chicken, and analyses of their mecA, mecR1 and mecI genes.
AB  - From 2001 to 2005, various specimens from cattle, pigs, and chickens were
      collected and examined for the presence of methicillin (oxacillin)-resistant
      Staphylococcus aureus (MRSA). The isolates from 19 specimens were tested for the
      presence of the mecA gene. Methicillin resistance was confirmed by determining
      the MICs for these isolates. Among these 19 mecA-positive isolates, 16 were
      consistently found to be resistant to methicillin. The mecR1 gene was found in
      all 19 mecA-positive S. aureus, and mecI was also detected in 15 of the mecA
      positive S. aureus. The mecI gene had an identical sequence to the reference
      sequence in 9 of the 15 mecI-positive isolates. Three of the other six isolates
      had a C to T substitution at nucleotide 202, and one had a G to T substitution at
      nucleotide 43. These have been previously identified in MRSA from humans. Two
      isolates from chickens contained an addition of C at position 23. This mutation
      of MRSA has not been reported elsewhere. In all 15 mecI-positive MRSA, the
      sequence of the mec promoter/operator region was identical to the reference
      sequence. This suggests other mechanisms for overcoming the repression of
      resistance caused by mecI, beyond the simple product interaction between the
      mecA, mecRI, and mecI genes.

PMID- 16625711
TI  - Home care not an exception for P4P shift.

PMID- 16625710
TI  - Spotlight on a young cardiologist. Interview by Monika Polak, PhD.

PMID- 16625713
TI  - Safe, safer, safest: the hierarchy of sexual risk behaviors for HIV.

PMID- 16625712
TI  - Inhaled beta agonists for chronic, nonspecific cough in children?

PMID- 16625714
TI  - The new sexual harm reduction.

PMID- 16625715
TI  - Serconversion narratives and insights for HIV prevention.

PMID- 16625716
TI  - Narrative competence psychotherapy for people with HIV.

PMID- 16625717
TI  - Immunity's yin and yang. A successful vaccine must first avoid being eliminated
      by pre-existing immunity before it can promote a protective immune response.

PMID- 16625718
TI  - Industrial strength research. Collaborative efforts in AIDS vaccine research are
      adopting some characteristics common in the biopharmaceutical industry.

PMID- 16625719
TI  - CROI covers advancements from start to finish. Highlights of recent HIV meeting
      run gamut from basic science to HIV prevention and vaccine research.

PMID- 16625720
TI  - HIV vaccine developments. An interview with Jose Esparza.

PMID- 16625721
TI  - Pharmexa-Epimmune initiates Phase I AIDS trial.

PMID- 16625722
TI  - Kenya begins enrollment for Phase I vaccine trial.

PMID- 16625723
TI  - Public health reports historical collection 1878-2005.

PMID- 16625724
TI  - Proceedings of the Endocrinopathy-Induced Osteoporosis 2nd National Meeting,
      Ancona, Italy, November 10-12, 2004.

PMID- 16625725
TI  - Extended abstracts of the annual meeting of the Working Group for Pharmacology in
      Oncology and Hematology (APOH) of the Central European Society for Anticancer
      Drug Research (CESAR), Vienna, Austria, 2005.

PMID- 16625726
TI  - Universal ethical principles in a diverse universe: a commentary on Monshi and
      Zieglmayer's case study.
AB  - Monshi and Zieglmayer's case study presents Sri Lankan participants as having
      views on the privacy of health information that differ radically from those
      commonly found in Western nations. This article explores 2 questions that their
      case study raises for the ethical review of research in international settings:
      First, are allegedly universal ethical principles--of the sort promulgated in the
      Belmont Report (National Commission for the Protection of Human Subjects of
      Biomedical and Behavioral Research, 1978)--useful in international settings?, and
      second, how should research oversight bodies address the challenges that arise in
      international behavioral and social science research?

PMID- 16625727
TI  - Human participants challenges in youth tobacco cessation research: researchers'
      perspectives.
AB  - Recruiting adolescents into smoking cessation studies is challenging,
      particularly given institutional review board (IRB) requirements for research
      conducted with adolescents. This article provides a brief review of the federal
      regulations that apply to research conducted with adolescents, and describes
      researchers' experiences of seeking IRB approval for youth cessation research.
      Twenty-one researchers provided information. The most frequently reported
      difficulty involved obtaining parental consent. Solutions to commonly reported
      problems with obtaining IRB approval are also identified. Waivers of parental
      consent can facilitate recruitment of youths into studies; however, researchers
      must ensure that their protocols comply with federal regulations when requesting
      a waiver.

PMID- 16625728
TI  - Human participants challenges in youth-focused research: perspectives and
      practices of IRB administrators.
AB  - The purpose of this research was to understand institutional review board (IRB)
      challenges regarding youth-focused research submissions and to present advice
      from administrators. Semistructured self-report questionnaires were sent via e
      mail to administrators identified using published lists of universities and
      hospitals an Internet searches. Of 183 eligible institutions, 49 responded. One
      half indicated they never granted parental waivers. Among those considering
      waivers, decision factors included research risks, survey content, and
      feasibility. Smoking and substance abuse research among children was generally
      considered more than minimal risk. These findings are consistent with those from
      a study conducted by Mammel and Kaplan (1995), which investigated IRB practices
      concerning protocols involving adolescent participants. IRBs and investigators
      need to become aware of regulations' flexibility to ensure adequate participant
      protection. Investigators need to limit jargon and assumptions about
      participants' understanding of research objectives.

PMID- 16625729
TI  - Ethics review of social, behavioral, and economic research: where should we go
      from here?
AB  - It is not unusual for researchers to complain about institutional review board
      (IRB) oversight, but social scientists have a unique set of objections to the
      work of ethics committees. In an effort to better understand the problems
      associated with ethics review of social, behavioral, and economic sciences (SBES)
      research, this article examinees 3 different aspects of research ethics
      committees: (a) the composition of review boards; (b) the guidelines used by
      these boards to review SBES--and in particular, behavioral health--research; and
      (c) the actual deliberations of IRBs. The article concludes with recommendations
      for changes in the review process and with suggestions for filling the gaps in
      knowledge about the way IRBs work.

PMID- 16625730
TI  - The journal club: a means to promote nursing research.

PMID- 16625731
TI  - New Year, new faces, new relationships.

PMID- 16625732
TI  - Public health nursing competencies.

PMID- 16625733
TI  - The nanny state meets the inner lawyer: overregulating while underprotecting
      human participants in research.
AB  - Without any systematic data or evidence of a problem, or even a thoughtful
      analysis of costs and benefits, the application of the human participant review
      system within universities is overreaching at the same time that some risky
      experimentation on humans outside of universities is unregulated. This article
      questions the purpose, feasibility, and effectiveness of current IRB approaches
      to most "2 people talking" situations and proposes scaling back the regulatory
      system to increase respect accorded it by researchers and its ability to protect
      human participants of research from real versus imagined harms. In too many
      cases, the focus is on form over ethical substance: counting what can be counted,
      rather than focusing instead on what counts. Some disciplines--oral history and
      journalism, for example--simply do not belong within the scope of institutional
      review board jurisdiction. Others, such as survey research, informational
      interviews, and informal interactions, call for a shift from centralized review
      to more departmentally based (i.e., rooted in disciplinary ethics) oversight, and
      clearer guidelines on what requires advance review as opposed to provision of
      post hoc complaint systems.

PMID- 16625734
TI  - Is compliance a professional virtue of researchers? Reflections on promoting the
      responsible conduct of research.
AB  - Evidence exists that behavioral and social science researchers have been
      frustrated with regulations and institutional review boards (IRBs) from the 1970s
      through today. Making matters worse, many human participants protection
      instruction programs--now mandated by IRBs--offer inadequate reasons why
      researchers should comply with regulations and IRBs. Promoting compliance either
      for its own sake or to avoid penalties is contrary to the developmental aims of
      moral education and may be ineffective in fostering the responsible conduct of
      research. This article explores the concept of professional virtue and argues
      that compliance is capable of becoming a professional virtue like scientific
      honesty. This requires, however, that regulatory and IRB demands contribute to
      human well-being and to the aims of research as a profession and that
      researchers, therefore, internalize the norms that underlie regulatory and IRB
      demands. This, in turn, requires a series of changes in the way society develops,
      promulgates, and enforces regulatory and IRB rules. The challenge is, simply put,
      to embed compliance into the world of living morality.

PMID- 16625735
TI  - Hierarchical protein identifications and assignments.

PMID- 16625736
TI  - Empirical research on research ethics.
AB  - Ethics is normative; ethics indicates, in broad terms, what researchers should
      do. For example, researchers should respect human participants. Empirical study
      tells us what actually happens. Empirical research is often needed to fine-tune
      the best ways to achieve normative objectives, for example, to discover how best
      to achieve the dual aims of gaining important knowledge and respecting
      participants. Ethical decision making by scientists and institutional review
      boards should not be based on hunches and anecdotes (e.g., about such matters as
      what information potential research participants would want to know and what they
      understand, or what they consider to be acceptable risks). These questions should
      be answered through empirical research. Some of the preceding articles in this
      special issue illustrate uses of empirical research on research ethics. This
      article places empirical research on research ethics into broader perspective and
      challenges investigators to use the tools of their disciplines to proactively
      solve ethical problems for which there currently exist no empirically proven
      solutions.

PMID- 16625737
TI  - Shaving proteins off the plasma membrane.

PMID- 16625738
TI  - Subcellular fractionation reveals proteins involved in insulin signaling.

PMID- 16625739
TI  - Practical ethics. Accept vendor dinner?

PMID- 16625740
TI  - Crohn's disease of the esophagus.

PMID- 16625741
TI  - Rotavirus vaccines.

PMID- 16625743
TI  - Rotavirus vaccines.

PMID- 16625742
TI  - Rotavirus vaccines.

PMID- 16625744
TI  - Proceedings from the French-Japanese Workshop on Muscular Dystrophies, July 1-2,
      2005, Paris, France.

PMID- 16625745
TI  - Intensive diabetes treatment and cardiovascular disease.

PMID- 16625746
TI  - Cryoplasty therapy.

PMID- 16625747
TI  - Patent foramen ovale and unexplained stroke.

PMID- 16625748
TI  - Physician assistants in radiology.

PMID- 16625749
TI  - Aneurysmal subarachnoid hemorrhage.

PMID- 16625750
TI  - Aneurysmal subarachnoid hemorrhage.

PMID- 16625752
TI  - Abstracts of the 26th Annual Conference on Peritoneal Dialysis, February 26-28,
      2006, San Francisco, California, USA.

PMID- 16625753
TI  - Abstracts of the American Society for Laser Medicine and Surgery 26th Annual
      Meeting, Boston, Massachusetts, USA, April 5-9, 2006.

PMID- 16625751
TI  - Aneurysmal subarachnoid hemorrhage.

PMID- 16625755
TI  - Conducting (paperless) research.

PMID- 16625754
TI  - Abstracts of the 7th Congress of the European Federation of National Associations
      of Orthopaedics and Traumatology, Lisbon, Portugal, 4-7 June 2005.

PMID- 16625756
TI  - Sexuality after ostomy surgery.

PMID- 16625758
TI  - For the little people.

PMID- 16625757
TI  - Xerosis and pruritus in elderly patients, Part 2.

PMID- 16625759
TI  - Chronic pain relief without drug risks.

PMID- 16625760
TI  - [Abstracts of the 20th Congress of the German-speaking Society of Intraocular
      Lens Implantation and Refractive Surgery. 3-4 March 2006, Heidelberg, Germany].

PMID- 16625762
TI  - Can ions in a spectrum be restored by a software setting to produce the proper
      mass spectrum?

PMID- 16625761
TI  - Bibliography. Current world literature. Behavioural medicine.

PMID- 16625763
TI  - Message from the vice president. Article: evolving and emerging roles in nursing.

PMID- 16625764
TI  - Collins on current issues: specialty certification in nursing: a hallmark of
      excellence.

PMID- 16625765
TI  - School nursing: advancing the well being and academic success of children.

PMID- 16625766
TI  - Specialty: autism approaches need to be tailored to each person.

PMID- 16625767
TI  - Nursing forensics: "CSI"-like techniques with one exception: live patients.

PMID- 16625768
TI  - Assisted living: the specialty of home care nursing.

PMID- 16625769
TI  - Long-term care nursing: a continuous evolution.

PMID- 16625770
TI  - Oncology nursing: maintaining quality of life for cancer patients.

PMID- 16625771
TI  - Advanced practice nursing: wound, ostomy, continence: a role for the new century.

PMID- 16625772
TI  - Pediatric nursing: nurse practitioner provides holistic care for the entire
      family.

PMID- 16625773
TI  - Nursing specialty: what is nursing informatics?

PMID- 16625774
TI  - Fitness nursing: a specialty for the 21st century.

PMID- 16625775
TI  - Community acquired methicillin-resistant Staphylococcus aureus update.

PMID- 16625776
TI  - Community acquired methicillin-resistant Staphylococcus aureus update--skin
      infection.

PMID- 16625778
TI  - [A society for French nurses].

PMID- 16625779
TI  - [Prevention of cardiovascular disease].

PMID- 16625780
TI  - [Handwashing: products better suited to nurses].

PMID- 16625781
TI  - [An essential step in immobilized patients].

PMID- 16625783
TI  - [Who ever sees veins will see pains: venous insufficiency].

PMID- 16625785
TI  - [Imaging specifically for women].

PMID- 16625786
TI  - [Tobramycin by inhalation].

PMID- 16625787
TI  - Individual rights? Public responsibility? Public health in the balance.

PMID- 16625788
TI  - Does affluence affect allergy preparedness?

PMID- 16625789
TI  - The effect of income on anaphylaxis preparation and management plans in Toronto
      primary schools.
AB  - BACKGROUND: Outcomes of serious allergic reactions are worse at school than at
      home. Prompt administration of epinephrine is the first-line treatment for
      anaphylactic reactions, and the EpiPen device is not subsidized by Ontario public
      health insurance. This study examines the relationship between the proportion of
      low-income households in Toronto neighbourhoods and the adequacy of anaphylaxis
      management plans in primary schools. METHODS: A survey was administered to
      principals of primary schools. It addressed the areas of: prevalence of food
      allergy, the presence of EpiPen at school and staff training in its use, and
      exposure prevention policy. The results were correlated to 2001 Canadian Census
      data for percentage of low-income households in each school's area. RESULTS:
      Children with reported severe food allergy attending schools in areas with
      greater than 20% low-income households were less likely to have medication at
      school than those in neighbourhoods with less than 20% (relative risk 2.2, 95%
      confidence interval 1.1-4.4). Other aspects of the anaphylaxis action plan,
      including staff EpiPen training and parental provision of information to the
      school, showed no significant correlation to income. Overall, about 50% of
      schools have their entire teaching staff trained to administer the EpiPen.
      INTERPRETATION: The lack of medication at school for anaphylaxis is a limiting
      factor in optimal anaphylaxis management in the school setting. Government
      support in the purchase of EpiPen in low-income households may be indicated.

PMID- 16625790
TI  - Infectious disease outbreaks related to drinking water in Canada, 1974-2001.
AB  - BACKGROUND: Recent public attention on drinking water supplies in the aftermath
      of waterborne infection outbreaks in Walkerton and North Battleford raises
      questions about safety. We analyzed information on waterborne outbreaks occurring
      between 1974 and 2001 in order to identify apparent trends, review the current
      status of monitoring and reporting, and gain a better understanding of the impact
      of drinking water quality on public health and disease burden. METHODS: Data from
      outbreak investigations, published and unpublished, were categorized by the type
      of drinking water provider and were assessed to be definitely, probably or
      possibly waterborne in nature. RESULTS: The final data set consisted of 288
      outbreaks of disease linked to a drinking water source. There were 99 outbreaks
      in public water systems, 138 outbreaks in semi-public systems and 51 outbreaks in
      private systems. The main known causative agents of waterborne disease outbreaks
      were (in descending frequency of occurrence) Giardia, Campylobacter,
      Cryptosporidium, Norwalk-like viruses, Salmonella and hepatitis A virus. SUMMARY:
      We found that severe weather, close proximity to animal populations, treatment
      system malfunctions, poor maintenance and treatment practices were associated
      with the reported disease outbreaks resulting from drinking water supplies.
      However, issues related to the accuracy, co-ordination, compatibility and detail
      of data exist. A systematic and coordinated national surveillance system for
      comparison purposes, trend identification and policy development is needed so
      that future waterborne disease outbreaks can be avoided.

PMID- 16625791
TI  - Effect of screening result on waiting times to assessment and breast cancer
      diagnosis: results from the Ontario Breast Screening Program.
AB  - BACKGROUND: The effect of severity of screening result on delays to diagnosis has
      primarily been examined for mammographic abnormalities. This study will examine
      delays to assessment and diagnosis for women with an abnormal mammogram compared
      to women with an abnormal clinical breast examination (CBE) or abnormal CBE and
      mammogram. METHODS: Using data routinely collected by Ontario Breast Screening
      Program (OBSP), 12,675 women aged 50 to 69 with an abnormal screening result
      between January 1, 2000 and December 31, 2000 were followed prospectively to the
      completion of their assessment process. Median waiting times from abnormal screen
      to first assessment procedure and diagnosis were compared by modality of referral
      and among women with a breast cancer diagnosis by prognostic features. RESULTS:
      The median waiting time to first assessment and to diagnosis was significantly
      longer for women with only a clinical abnormality compared to women with a
      mammographic abnormality. In addition, women diagnosed with cancers of larger
      size had longer delays when the abnormality was detected only clinically.
      However, women referred by both modalities had significantly shorter waiting
      times to first assessment procedure and to diagnosis of poor prognosis cancers
      compared to women referred by mammography alone. INTERPRETATION: Women with an
      abnormal CBE and mammogram are assessed more promptly and have shorter diagnostic
      times. However, women with only a CBE abnormality had delays to diagnosis as a
      result of longer waiting times to first assessment procedure. Integration of the
      OBSP with assessment centres should improve times to diagnosis irrespective of
      modality of referral.

PMID- 16625792
TI  - Proportion of cancer deaths occurring in hospital, Canada, 1994-2000.
AB  - BACKGROUND: Most terminally ill cancer patients would prefer not to die in
      hospital, but only a minority achieve their wish. Our objective was to examine
      the proportion of cancer deaths occurring in Canadian hospitals. METHODS: The two
      sources of data (1994-2000) were: 1) all hospital separations (HS) with a primary
      diagnosis of cancer and discharge as 'dead'; 2) all death certificates (DC) with
      cancer as underlying cause of death. Proportions of hospital deaths were
      estimated with two different numerators: 1) hospital cancer deaths from HS data,
      and 2) deaths with hospital as location from DC data; the denominator for both
      were all cancer deaths identified from the DC data. RESULTS: Proportions of
      hospital deaths from HS data decreased from 55% to 40% over 1994-2000, was
      slightly lower for females, decreased with age, but varied widely among
      provinces. Proportions of hospital deaths from DC data started at 80% and showed
      a small downward trend over the years. While age, sex, and cancer site
      distributions stayed the same, the proportion of hospital deaths from DC date
      again varied among provinces. For provinces with the home category completed on
      the DC data, 1999-2000, Alberta had most home deaths at 15.6% and PEI least at
      5.7%. INTERPRETATION: This is the first Canada-wide data on place of death for
      terminal cancer, which is important for determining and comparing present-day
      practices, as well as for planning for the future.

PMID- 16625793
TI  - [Usefulness of a vaccination registry and the management of consent: the case of
      Quebec].
AB  - CONTEXT: The Quebec Public Health Act provides for the creation of a central
      vaccination registry. However, details of how such a registry would be used have
      not been established. This study seeks to document the opinion of both the public
      and of health workers about the usefulness of the registry, consent for
      enrolment, access to the data and the right of withdrawal. METHODS: Individual
      interviews and discussion groups were held with parents, senior citizens and
      health workers. The material collected was recorded, transcribed and analyzed
      qualitatively using MAXQDA software. RESULTS: The usefulness of a vaccination
      registry seems to meet with general agreement, as does the idea of obtaining
      broad-based consent at enrolment. However, this consensus starts to crumble on
      questions of determining the rules governing access to the registry. Some favour
      limited consent, authorizing each access, while others, more numerous, prefer a
      broad-based consent giving access to all individuals authorized under the law.
      Opinions are even more divided on the question of giving the user the right to
      not record certain vaccines, particularly when they may be considered sensitive
      and a possible cause of prejudice. DISCUSSION: The more the information is
      considered sensitive by users, the more they seek to have access to the register
      and entries into it controlled and to apply some kind of specific consent,
      limited in scope, rather than a broad-based consent. This study lets us draw
      lessons applicable to the computerization and networking of medical records.

PMID- 16625794
TI  - [Portrait of the formation in vaccination training offered to Quebec nurses in
      the workplace].
AB  - INTRODUCTION: Nurses carry out essential functions in the area of immunization in
      Quebec and their role has broadened considerably since January 2003, following
      legislative modifications. However, the training received may not always allow
      nurses to fill this role satisfactorily. This study seeks to document the
      training in immunization offered to Quebec nurses in the workplace. METHOD: A
      questionnaire was mailed to the directors or heads of nursing care (DSI/RSI) in
      477 health care establishments in Quebec in March 2003. RESULTS: Health care
      establishments in Quebec offer more training to nurses on the job (68%) than at
      the moment of hiring (43%). These percentages vary widely according to the type
      of establishment. More than 90% of the local community service centres (CLSC)
      that responded offer training to their nurses. The indications/contraindications
      of immunization products and emergencies related to vaccination represent the
      themes most frequently dealt with. Only 38% of respondents affirm that the nurses
      in their institution are "very favourable" to vaccination. DISCUSSION: Almost all
      Quebec CLSCs, which is where most immunization activities are carried out, offer
      training in vaccination to their nurses. On the other hand, few hospital centres
      (CH) and long-term care establishments (CHSLD) do so. Further documentation
      should be carried out on the impact of less than optimal training on the
      promotion of immunization programs by nurses.

PMID- 16625795
TI  - The future of tobacco marketing in Canada.
AB  - With the advent of the Tobacco Act, tobacco marketing is now severely restricted
      in Canada. This article considers how the tobacco industry may conduct future
      marketing in order to circumvent the Tobacco Act. Past tobacco marketing
      strategies are discussed in light of how such strategies could be used in future
      marketing campaigns. In addition, this article highlights the need for private
      industries unrelated to tobacco to conduct socially responsible advertising so as
      to avoid inadvertently promoting tobacco.

PMID- 16625796
TI  - Legal foundations for a national public health agency in Canada.
AB  - This commentary addresses some of the key legal challenges associated with
      establishing a national public health agency in Canada. These include issues
      related to privacy and confidentiality of personal health information in the
      public health context, constraints on the jurisdiction and powers of a national
      agency, the need to respect individual rights and freedoms in an outbreak
      situation, and international cooperation in infectious disease control. The
      authors are part of a research initiative, comprised of experts in law, public
      health policy and medicine, that is currently analyzing legal considerations that
      may influence the mandate of a national public health agency in regard to
      infectious disease activities. This article discusses critical issues raised at a
      meeting in August 2004 that brought the research team together with key federal
      and provincial policy-makers and members of the public health community. The
      commentary emphasizes that law sets the foundation for public health activities,
      and the promise of a national public health agency will only be realized if
      significant legal issues are examined early on to ensure the agency is built on a
      robust legal and policy framework.

PMID- 16625797
TI  - Understanding and minimizing epidemiologic bias in public health research.
AB  - Awareness of potential biases is important for both researchers and policy-makers
      in public health: for researchers when designing and conducting studies, and for
      policy-makers when reading study reports and making decisions. This paper
      explains the meaning and importance of epidemiologic bias in public health and
      discusses how it arises and what can be done to minimize it. Examples of counting
      participants in a meeting, to which many policy-makers can relate, are used
      throughout the paper to illustrate bias in general, random error and systematic
      error, the effect of sample size, the three main categories of bias (selection,
      information and confounding), stratification and mathematical modeling.

PMID- 16625798
TI  - Child and adolescent health in Northern Ontario: a quantitative profile for
      public health planning.
AB  - Health in Northern Ontario is poorer than in the province of Ontario. Late
      childhood is the period in which adult habits and health behaviours are
      solidified, thus, health indicators are important to guide the development and
      implementation of disease prevention strategies. The Northern Ontario Child and
      Youth Health Report evaluated the health of children in Northern Ontario. The
      importance of public health planning is presented with the value of health status
      information for youth. The hospitalization rate for Northern Ontario youths was
      higher than for Ontario. In both areas, injuries and poisonings were the leading
      cause of hospitalization (7-13 year olds), however rates in the North were
      higher. Hospitalizations for injuries and poisonings were double the provincial
      rate in 14-19 year olds. The mortality rate for all youth was significantly
      higher. Health risk behaviour prevalence (e.g., alcohol consumption) was higher
      in the region. Current data emphasize the need for primordial and primary
      prevention in regional health planning and are also useful in secondary and
      tertiary prevention. Data for public health planning is critical to address
      population health needs and prevent chronic diseases.

PMID- 16625799
TI  - Re: conquering the crippler: Canada and the eradication of polio (insert). Can J
      Public Health 2005;96(2):I1-I24.

PMID- 16625800
TI  - The axis and nexus of e-health alliances in 2020.
AB  - Strategic partnerships between the health care and Information Communication
      Technology (ICT) sectors are the wave of the future, as e-health systems are
      implemented. Divergent perspectives between ICT and health care executives impose
      central challenges in forging productive strategic alliances. Bridging these
      perceptual differences requires strong leadership and vision, financial
      resources, and care provider support. Together these form the axis upon which
      tomorrow's e-health alliances will rest. The growth of e-health systems is
      inexorable. The strength of governance leadership continues to influence its rate
      of growth and positive impact on health care systems. The extent to which
      strategic partnerships with the ICT sector will evolve into dynamic e-health
      alliances is directly related to the quality of national and regional governance
      leadership--the ultimate nexus of evolving e-health systems of 2020.

PMID- 16625801
TI  - A community-based program for cardiovascular health awareness.
AB  - OBJECTIVE: The objective of the Cardiovascular Health Awareness Program (CHAP) is
      to improve the processes of care related to the cardiovascular health of older
      adults. PARTICIPANTS: Two Ontario communities including family physicians (FP),
      pharmacists, public health units and nurses, volunteer peer health educators,
      older adult patients and community organizations. SETTING: Community pharmacies
      and family physician offices. INTERVENTION: CHAP is designed to close a process
      of care loop around cardiovascular health awareness that originates from, and
      returns to, the FP. Older patients are invited by their FP to attend pharmacy
      CHAP sessions. At these sessions, trained volunteer peer health educators (PHEs)
      assist patients both in recording their blood pressure using a calibrated
      automated device and in completing a cardiovascular risk profile. This
      information is relayed to their respective FP via an automated computerized
      database. Pharmacists and patients receive copies of the results. Based on these
      cumulative risk profiles, patients are advised to follow-up with their FP.
      OUTCOMES: Of the FPs and pharmacists asked, 47% and 79%, respectively, agreed to
      participate in the project. 39% of older adult patients invited by their FPs
      attended the CHAP community pharmacy sessions. Of these, 100% agreed to having
      their risk profile, including their blood pressure readings, forwarded to their
      FP. Positive feedback about CHAP was expressed by the volunteer PHEs, the FPs and
      the pharmacists. CONCLUSION: The community-based pharmacy CHAP sessions are a
      feasible way of improving patient, physician, and pharmacist access to reliable
      blood pressure measurements and to cardiovascular health information. A
      randomized trial is in progress that will assess the impact of CHAP on monitoring
      of blood pressure.

PMID- 16625802
TI  - Preschoolers' physical activity behaviours: parents' perspectives.
AB  - OBJECTIVES: To understand parents' perspectives of their preschoolers' physical
      activity behaviours. METHODS: A maximum variation sample of 71 parents explored
      their preschoolers' physical activity behaviours through 10 semi-structured focus
      group discussions. RESULTS: Parents perceived Canada's Physical Activity
      Guidelines for Children as inadequate; that their preschoolers get and need more
      than 30-90 minutes of activity daily; and that physical activity habits must be
      established during the preschool years. Nine barriers against and facilitators
      toward adequate physical activity were proposed: child's age, weather, daycare,
      siblings, finances, time, society and safety, parents' impact, and child's
      activity preferences. DISCUSSION: The need for education and interventions that
      address current barriers are essential for establishing physical activity as a
      lifestyle behaviour during early childhood and, consequently, helping to prevent
      both childhood and adulthood obesity.

PMID- 16625803
TI  - Iron deficiency and anemia prevalence and associated etiologic risk factors in
      First Nations and Inuit communities in Northern Ontario and Nunavut.
AB  - BACKGROUND: Anemia is common among children in Aboriginal communities in Canada.
      The objectives of this study were to determine the prevalence of anemia and to
      identify its associated risk factors among young children in Aboriginal
      communities in northern Ontario and Nunavut. METHODS: 115 children from one Inuit
      and two Cree First Nations communities participated. We collected information on
      demographic and dietary factors and measured hemoglobin (Hb), ferritin (SF),
      serum transferrin receptor (sTfR) and Helicobacter pylori IgG antibodies. Odds
      ratios and 95% confidence intervals were determined to examine risk factors
      associated with anemia and iron deficiency (ID) and further analyzed using
      stepwise regression procedures. RESULTS: Prevalence of anemia (Hb<110 g/L) was
      36.0%. Iron deficiency (sTfR>8.5 mg/L) was present in 27.6% of the study
      population. Approximately 53.3% had depleted iron stores (SF<12 microg/L).
      Consumption of cow/evaporated milk was the only independent risk factor
      associated with anemia. Infection with H. pylori and prolonged consumption of
      breastmilk were also associated, although not independently, with anemia. Formula
      intake was negatively associated with ID. INTERPRETATION: The prevalence of
      anemia in Aboriginal children was eight times higher than among similar
      populations in urban Canada and was especially high among Inuit children. ID was
      the major cause of anemia, but not the only one, since 10% of anemic children
      were not iron deficient. Given that the consumption of cow/evaporated milk was
      found to be a significant independent risk factor associated with anemia, public
      health strategies should include promotion of breastfeeding, combined with iron
      rich complementary foods, while addressing socio-economic conditions that may be
      preventing these practices from being adopted. H. pylori may be a major
      contributing factor to anemia, thus improvements in water quality and sanitation
      also need to be considered.

PMID- 16625804
TI  - Falling through the cracks of the big cities: who is meeting the needs of HIV
      positive youth?
AB  - BACKGROUND: Globally, half of all new HIV infections occur among youth under 25.
      As of June 30, 2002, more than 13,000 youth and young adults had tested positive
      for HIV in Canada. Despite this prevalence, there is a lack of resources for
      Canadian HIV-positive youth. OBJECTIVE: To investigate what can be done to better
      support the needs of HIV-positive youth in Canada. METHODS: A community-based
      participatory research approach was adopted. Thirty-four qualitative in-depth
      semi-structured interviews were conducted with youth (ages 12-24) living with HIV
      in Ontario. A stakeholder group of youth living with HIV, professionals and
      researchers collaboratively analyzed the data for emerging themes. RESULTS: When
      asked about areas in their lives where youth needed support, three major themes
      emerged: 1) Personal feelings about HIV: Youth identified a wide range of
      emotional response to their HIV status; however feelings of isolation, loneliness
      and hopelessness were dominant. 2) Barriers to full participation in society:
      Youth described a number of social and structural barriers to their full
      participation in society. 3) Specific support needs: Youth had difficulty
      accessing appropriate support services; they had very mixed feelings about both
      youth- and AIDS-serving organizations. INTERPRETATION: The youth we interviewed
      are interested in targeted programs, have difficulty accessing appropriate
      resources and would benefit greatly from increased social support. Specialized
      health and support services that are developmentally appropriate may be
      necessary. Where specialized services do exist, more research may be necessary to
      understand why they are underutilized and/or perceived as inappropriate. While
      this was a small exploratory study, our data suggest that better supporting the
      needs of HIV-positive youth might directly benefit this vulnerable population.

PMID- 16625805
TI  - Socio-economic factors and adolescent sexual activity and behaviour in Nova
      Scotia.
AB  - PURPOSE: Little is known about associations of adolescents' socio-economic status
      (SES) and their sexual activity and risk behaviours. This study examined these
      associations in Nova Scotia adolescents aged 15-19. METHODS: Students at four
      high schools in northern Nova Scotia completed surveys examining relationships of
      family SES factors and: 1) sexual activity (having had vaginal or anal
      intercourse, intercourse before age 15 (early intercourse)); and 2) risk
      behaviours (use of contraception/condoms, number of partners and unplanned
      intercourse after substance use). RESULTS: Of students present when the survey
      was administered, 2,135 (91%) responded. Almost half (49%) had had vaginal
      intercourse, and 7% anal intercourse. In univariate analysis for young women, non
      intact family structure and lower parental education were associated with having
      vaginal, anal and early intercourse. Female risk behaviours showed no significant
      univariate associations with SES. Young men had univariate associations of family
      structure, lower maternal education and paternal unemployment with early
      intercourse, and lower paternal education with anal intercourse. Condom use was
      higher for young men with employed fathers; those living with both parents less
      often had >1 sexual partner. In multivariate analysis, most SES associations with
      females' sexual activities held, while most for males did not, and few
      associations of SES and risk behaviours were seen for females. CONCLUSIONS:
      Indicators of lower SES are associated with sexual activity in young women.
      Sexual risk behaviours are not often associated with SES in females, though they
      are more so in males. These findings have implications for sexual health
      promotion and health services.

PMID- 16625806
TI  - Tightening seat belts.

PMID- 16625807
TI  - Benefiting from an IRA rollover.

PMID- 16625808
TI  - Factors related to women's decisions to smoke during their pregnancies.

PMID- 16625809
TI  - Overuse-related vascular injury of the hand--hypothenar hammer syndrome: a case
      report.
AB  - Although rare, vascular insufficiency is a well-recognized cause of hand pain,
      making a significant impact in the athletic and labor industry. Surgically
      correctable lesions are important to recognize since definitive treatment may
      alter the course of the disease and affect outcomes. Hypothenar hammer syndrome
      (HHS) results from anatomic predisposition and exposure to acute and chronic
      stress. Arteriography is the gold standard of diagnosis and severe symptomatic
      cases are treated with surgical resection and re-establishment of blood flow. We
      report such a case of HHS, its clinical course and management.

PMID- 16625810
TI  - Giant aneurysm of the saphenous vein graft presenting as a mediastinal mass: a
      case report.
AB  - We report a patient who presented initially with a diagnosis of a mediastinal
      mass. During the cardiac catheterization, the patient was diagnosed with a
      saphenous vein graft aneurysm. We proceeded with a catheter-based intervention
      resulting in occlusion of the aneurysm. Repeat angiogram after three months
      showed complete occlusion of the vein graft supplying the aneurysm. We believe
      that in selected patients with saphenous vein graft aneurysm a catheter-based
      procedure is feasible and successful.

PMID- 16625811
TI  - The prevalence of viral hepatitis and HIV infections in patients with congenital
      bleeding disorders.
AB  - Patients with clotting disorders, including hemophilias A and B, and von
      Willebrand Disease generally receive pooled human blood products, and are at high
      risk for HIV-1 and hepatitis A, B and C viral infection. This retrospective study
      describes patients receiving treatment at a federally funded Hemophilia Treatment
      Center (HTC) from 1998 - 2002 and assesses the prevalence of viral infection. In
      addition, current rates of viral infection are compared to 1984-1996 rates.

PMID- 16625812
TI  - The use of botulinum toxic injection to treat excessive drooling in children with
      neurological conditions.
AB  - Drooling is a frequent complaint in children with chronic neurological
      conditions. This is due to poor neuromuscular coordination of the oropharyngeal
      musculature. Treatment options such as anticholinergic medications and surgical
      treatment have generally been unsuccessful or associated with side effects and
      complications. A new treatment for these children is botulinum toxin injection
      into the parotid glands to decrease saliva production. This article reports on
      two cases in which this modality was effectively utilized to treat this
      neurological condition.

PMID- 16625813
TI  - The multiple challenges in the management of a patient with HELLP syndrome, liver
      rupture and eclampsia.
AB  - We report a case of a patient with HELLP syndrome, hemorrhagic shock due to liver
      rupture and late postpartum eclampsia superimposed on lupus nephropathy and
      chronic hypertension. This patient was delivered at 26 weeks by C-section.
      Aggressive and complex surgical and medical treatments were necessary to achieve
      hemostasis and stabilize the patient. She recovered and was discharged to home on
      the 24th postpartum day in good condition. The premature baby was discharged home
      in fair condition on the 131st hospital day.

PMID- 16625814
TI  - Governor Manchin to receive AMA's highest award.

PMID- 16625815
TI  - Non-gene therapy for genetic diseases.

PMID- 16625816
TI  - The role of resistin in obesity-induced insulin resistance.
AB  - Resistin is a 12.5-kDa polypeptide hormone produced by adipocytes and
      immunocompetent cells. It was originally proposed as a link between obesity and
      insulin resistance/diabetes. Later, studies revealed that substantial inter
      species differences exist between the major sites of resistin production in
      rodents (adipocytes) and humans (immunocompetent cells). While in rodents
      resistin appears to have an important role in the development of liver insulin
      resistance, its role in humans is less clear, and it is probably involved in the
      regulation of inflammatory processes rather than in insulin sensitivity. Current
      experimental and clinical data concerning resistin physiology and
      pathophysiology, and its possible role in the development of insulin resistance
      and atherosclerosis are detailed in this review.

PMID- 16625817
TI  - Obesity drugs in clinical development.
AB  - A number of anti-obesity drugs are currently undergoing clinical development.
      These include: (i) centrally-acting drugs, such as the noradrenergic and
      dopaminergic reuptake inhibitor radafaxine, the endocannabinoid antagonist
      rimonabant, the selective serotonin 5-HT2c agonist APD-356, and oleoyl-estrone;
      (ii) drugs that target peripheral episodic satiety signals, such as glucagon-like
      peptide-1 (exenatide, exenatide-LAR and liraglutide), peptide YY (intranasal PYY3
      36 and AC-162325) and amylin (pramlintide); (iii) drugs that block fat
      absorption, such as the novel lipase inhibitors cetilistat and GT-389255; and
      (iv) a human growth hormone fragment (AOD-9604) that increases adipose tissue
      breakdown. Of these, only rimonabant has got as far as completing phase III
      clinical trials. This review will provide an overview of the most prominent drugs
      currently undergoing clinical development as potential anti-obesity therapies.

PMID- 16625818
TI  - Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 for the treatment of
      metabolic syndrome.
AB  - Metabolic syndrome is a group of metabolic abnormalities associated with
      increased cardiovascular and mortality risks. Glucocorticoid excess has been
      linked to the development of metabolic syndrome. Intracellular glucocorticoid
      levels are regulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD
      1), a key enzyme that converts inert cortisone to active cortisol. To counter the
      unfavorable metabolic effects of glucocorticoids in certain tissues, 11beta-HSD-1
      inhibitors are being investigated for their potential in the treatment of insulin
      resistance and other aspects of metabolic syndrome. Several different classes of
      11beta-HSD-1 inhibitors are currently under investigation by multiple
      pharmaceutical companies, highlighting the encouraging progress made in this
      field.

PMID- 16625819
TI  - Pathological mechanisms involved in diabetic neuropathy: can we slow the process?
AB  - Diabetic polyneuropathy (DPN) is the most common late diabetic complication, and
      is more frequent and severe in the type 1 diabetic population. Currently, no
      effective therapy exists to prevent or treat this complication. Hyperglycemia
      remains a major therapeutic target when dealing with DPN in both type 1 and type
      2 diabetes, and should be supplemented by aldose reductase inhibition and
      antioxidant treatment. However, in the past few years, preclinical and clinical
      data have indicated that factors other than hyperglycemia contribute to DPN, and
      these factors account for the disproportionality of prevalence of DPN between the
      two types of diabetes. Insulin and C-peptide deficiencies have emerged as
      important pathogenetic factors and underlie the acute metabolic abnormalities, as
      well as serious chronic perturbations of gene regulatory mechanisms, impaired
      neurotrophism, protein-protein interactions and specific degenerative disorders
      that characterize type 1 DPN. It has become apparent that in insulin-deficient
      conditions, such as type 1 diabetes and advanced type 2 diabetes, both insulin
      and C-peptide must be replaced in order to gain hyperglycemic control and to
      combat complications. As with any chronic ailment, emphasis should be on the
      prevention of DPN; as the disease progresses, metabolic interventions, be they
      directed against hyperglycemia and its consequences or against insulin/ C-peptide
      deficiencies, are likely to be increasingly ineffective.

PMID- 16625820
TI  - Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2
      diabetics via incretin enhancement.
AB  - Incretin levels approach normal physiological values following treatment with
      dipeptidyl peptidase (DPP)-IV inhibitors. This is in contrast to incretin levels
      resulting from the exogenous administration of glucagon-like peptide (GLP)-1 and
      its analogs, which can reach super-physiological values. This review describes
      the role of DPP-IV inhibitors as incretin enhancers in the regulation of glucose
      homeostasis in type 2 diabetic patients. The roles of incretins and the effect of
      DPP-IV on their actions are described, as are new therapeutic interventions based
      on the restoration of impaired incretin secretion in type 2 diabetic patients and
      obese individuals. In addition, the relevance of DPP-IV inhibition for weight
      control, its potential influence on beta-cell mass, and possible new indications
      are discussed, as are the implications of the currently available clinical data.

PMID- 16625821
TI  - New targets in and potential treatments for cholesterol gallstone disease.
AB  - Gallstone disease is very common among American Indians and Hispanics, and
      approximately 20 million patients are treated for this disease annually in the
      US. Bile acid receptor (nuclear farnesoid X receptor; FXR) knockout mice fed a
      lithogenic diet are more susceptible to gallstone disease than wild-type mice.
      The C57L mouse is also susceptible to gallstone formation when fed a lithogenic
      diet, and in this model, the small-molecule FXR agonist GW-4064 prevents the
      precipitation of cholesterol. Bile acids (eg, P-muricholic acid) and their
      derivatives are also being developed as FXR agonists. Fatty acid bile acid
      conjugates have the potential to prevent and reverse cholesterol crystallization.
      Furthermore, agents that increase the expression of selected hepatocyte bile acid
      transporters may also be useful in the treatment of gall bladder disease.

PMID- 16625822
TI  - Osteoporosis-treating parathyroid hormone peptides: What are they? What do they
      do? How might they do it?
AB  - The first experiments demonstrating parathyroid hormone's (PTH's) dramatic bone
      building activity in rat pups, using a bovine parathyroid extract called
      parathormone were reported 74 years ago. Over the next decades, the native
      parathyroid hormone (human (h)PTH(1-84)) was purified and two of its fragments
      (hPTH(1-34) and (Leu27)cycloGlu22-Lys26hPTH(1-31)NH2) have been developed for the
      treatment of osteoporosis. One of these, recombinant (r)hPTH(1-34), is now on the
      market under the trade name of Forteo. The native hormone has also completed
      clinical trials and (Leu27)cycloGlu22-Lys26hPTH(1-31)NH2 is in phase II clinical
      trials under the trade name Ostabolin-C. All three of these peptides potently
      stimulate bone growth, reinforce bone microstructure weakened by estrogen
      deprivation and reduce further fracturing. Furthermore, future studies may
      demonstrate that these peptides also promote the repair of existing fractures and
      implant anchorage in both healthy and osteoporotic humans. PTHs have the
      potential to become more successful by using cost-cutting, but still effective,
      cyclical treatment regimens and by formulating them for non-injectable delivery.
      This review will discuss the identification of PTH peptides, how they function
      and their future role in the treatment of osteoporosis.

PMID- 16625823
TI  - GW-501516 GlaxoSmithKline/Ligand.
AB  - GlaxoSmithKline and Ligand are developing GW-501516, a peroxisome proliferator
      activator receptor-delta agonist for the potential treatment of dyslipidemia.
      Phase II clinical trials of this compound are ongoing.

PMID- 16625824
TI  - Mecasermin Tercica.
AB  - Tercica, under license from Genentech, has developed and launched mecasermin,
      recombinant human insulin-like growth factor-1 (rhIGF-1), for the treatment of
      growth failure in children with primary IGF deficiency or with growth hormone
      (GH) gene deletion who have developed neutralizing antibodies to GH.

PMID- 16625825
TI  - Anti-CD3 antibody MacroGenics Inc.
AB  - A non-FcR-binding anti-CD3 monoclonal antibody, hOKT3gamma1 (Ala-Ala), originally
      developed by Columbia University, is being developed by MacroGenics for the
      potential treatment of type 1 diabetes and autoimmune diseases. Phase I/II trials
      in patients with diabetes have been completed, and a phase II clinical trial in
      psoriatic arthritis was initiated in October 2005. A Phase II trial that will
      evaluate a multi-course study of the drug in patients with new-onset diabetes
      began in March 2006. MacroGenics is currently seeking to outlicense the project
      to a strategic partner.

PMID- 16625826
TI  - Research advances on transgenic plant vaccines.
AB  - In recent years, with the development of genetics molecular biology and plant
      biotechnology, the vaccination (e.g. genetic engineering subunit vaccine, living
      vector vaccine, nucleic acid vaccine) programs are taking on a prosperous
      evolvement. In particular, the technology of the use of transgenic plants to
      produce human or animal therapeutic vaccines receives increasing attention.
      Expressing vaccine candidates in vegetables and fruits open up a new avenue for
      producing oral/edible vaccines. Transgenic plant vaccine disquisitions exhibit a
      tempting latent exploiting foreground. There are a lot of advantages for
      transgenic plant vaccines, such as low cost, easiness of storage, and convenient
      immune-inoculation. Some productions converged in edible tissues, so they can be
      consumed directly without isolation and purification. Up to now, many transgenic
      plant vaccine productions have been investigated and developed. In this review,
      recent advances on plant-derived recombinant protein expression systems,
      infectious targets, and delivery systems are presented. Some issues of high
      concern such as biosafety and public health are also discussed. Special attention
      is given to the prospects and limitations on transgenic plant vaccines.

PMID- 16625827
TI  - Molecular cloning and preliminary function study of a novel human gene, TSARG7,
      related to spermatogenesis.
AB  - A novel human gene TSARG7 (GenBank accession No. AY513610) was identified from a
      human testis cDNA library by using the mTSARG7 gene (GenBank accession No.
      AY489184) as an electronic probe. The gene whose full cDNA length is 2,463 bp
      containing 12 exons and 11 introns is located in the human chromosome 8p11.21.
      The predicted protein encoded by this gene contains 456 amino acids with a
      theoretical molecular weight of 56,295 dalton and isoelectric point of 9.13. It
      is a new member of the acyltransferase family since its sequence possesses the
      highly conserved PlsC domain existing in all acyltransferase-like proteins. Two
      groups, the TSARG7 and mTSARG7, the TSARG7 and Au041707, share 97% identity in
      the 456 amino acids. Expression of the TSARG7 gene is restricted to the testis.
      Subcellular localization studies show that the EGFP-tagged TSARG7 protein was
      localized in the cytoplasm of GC-1 cells. The TSARG7 mRNA expression was
      initiated in the testis of a 13-year-old boy, and its level increased steadily
      along with spermatogenesis and sexual maturation of the human. The results of
      heat stress experiment demonstrate that TSARG7 expression has a relation with
      temperature. In conclusion, our study suggests that we have cloned a novel human
      gene and this gene may play an important role in human spermatogenesis and sexual
      maturation.

PMID- 16625828
TI  - Evidence of different ploidy eggs produced by diploid F2 hybrids of Carassius
      auratus (female) x Cyprinus carpio (male).
AB  - Based on the presence of three types of eggs with different diameters 0.13, 0.17
      and 0.2 cm, we made two crosses: F2 (female) x diploid red crucian carp (male),
      and F2 (female) x F10 tetraploid (male). The ploidy levels of the progeny of the
      two crosses were examined by chromosome counting and DNA content measurement by
      flow cytometer. In the offspring of the former cross, tetraploids, triploids, and
      diploid were obtained. In the progeny of the latter cross, tetraploids and
      triploids were observed. The production of the different ploidy level fish in the
      progeny of the two crosses provided a further evidence that F2 might generate
      triploid, diploid and haploid eggs. The presence of the male tetraploid found in
      F2 (female) x diploid red crucian carp (male) suggested that the genotype of XXXY
      probably existed in the tetraploid progeny. The gonadal structures of the
      tetraploids and triploids indicated that both female and male tetraploids were
      fertile and the triploids were sterile. We concluded that the formations of
      different ploidy level eggs from F2 were contributed by endoreduplication and
      fusion of germ cells.

PMID- 16625829
TI  - Changes in variance components of flanking marker genotypes under varying
      selection intensities.
AB  - Selection is practically ubiquitous during marker-QTL linkage analysis with an
      experimental population. Thus, it is necessary to investigate the impacts of
      selection upon linkage analyses in order to obtain unbiased estimates of QTL
      position and effect. In this article, by exploiting flanking markers through the
      widely applied half-sib design, we have developed the structures of three
      variance components, i.e., variance component between marker genotypes, polygenic
      variance component and recombinant variance component within marker genotypes.
      Changes in these variance components under varying selection intensities were
      investigated in this study to formulate the effects of selection on various
      variance components. Results showed clearly that all variance components
      presented were quite sensitive to changes in selection intensity. As selection
      intensity increased, all variance components declined by differing extents in a
      quadratic fashion. Comparatively speaking, the variance between marker genotypes
      decreased most drastically, followed by the polygenic variance within marker
      genotypes and then the recombinant variance within marker genotypes, which
      suggested a decrease of power for QTL linkage analysis. Therefore, steps should
      be taken to avoid as much as possible the presence of selection in real
      populations, so as to further eliminate the negative effects of selection on QTL
      linkage analysis.

PMID- 16625830
TI  - Screening for and genetic analysis on T-DNA-inserted mutant pool in rice.
AB  - T-DNA tagging technique has provided a powerful strategy for identifying new
      functional genes in plants, and the key for success is the discovery of T-DNA
      inserted mutants with changed phenotype. In this study, we screened 4,416 rice T1
      tagged lines generated by enhancer trap system integrated with GLL4/VP16-UAS
      elements from two transformed parents, ZH11 and ZH15. We found many lines showed
      obvious morphological mutations, including two types--fake-homozygous mutation
      and separating mutation. The mutation phenotype was related to 14 kinds of trait
      such as plant height, heading date, leaf shape, leaf color, tiller number,
      panicle shape, spikelet number, grain shape, disease-like mutation, male
      sterility, awn, and so on. Among them, plant height, heading date, leaf color and
      male sterility had a comparatively high mutation frequency (over 1%). The
      mutation frequency of plant height and leaf color had no significant change
      between different years or transformed parents, but the frequency of heading date
      and male sterility varied greatly, suggesting that environment had a great effect
      on the expression of latter two traits. By conducting continuously co-segregating
      analyses in T1 and T2 generation, we identified 3 T-DNA-inserted mutants with
      malformed panicle or spikelets, which would provide a base for cloning
      correlative functional genes. At the same time, we selected randomly 42 lines
      with mutation phenotype and obtained 40 flanking sequences from 39 tagged lines
      by plasmid rescue or TAIL-PCR, of which, 26 were vector backbone sequence, 14 had
      good identity to rice genome sequence. The BlastN result showed the T-DNA
      preferentially integrated into protein-coding region in plants.

PMID- 16625831
TI  - RFLP analysis for mitochondrial genome of CMS-rice.
AB  - Restriction fragment length polymorphism (RFLP) was used to analyze mitochondrial
      (mt) genome of cytoplasmic male sterility (CMS) rice. Differences were observed
      among mitochondrial genomes of the sterile line (A) and maintain line (B) of nine
      types of CMS rice; Mitochondrial genomic differences were also detected between A
      and B in many functional gene regions. Even the materials with the same nucleic
      background have differences in their mtDNA. This provides molecular evidence for
      the cytoplasmic heterogeneity and the CMS mechanism research.

PMID- 16625832
TI  - Genetic analysis and molecular tagging on a novel excessive tillering mutant in
      rice.
AB  - A rice (Oryza sativa L.) mutant with an excessive tiller number, designated ext
      M1B, was found in the F2 progenies generated from the cross between M1B and GMS-1
      (a genetic male sterile), whose number of tillers was 121. The excessive
      tillering mutant also resulted in significant changes in plant height, flag leaf,
      stem, filled grains per panicle, and productive panicles per plant. The
      inbreeding progenies of ext-M1B exhibited the same mutant phenotype. The crosses
      from ext-M1B/M1B, M1B/ext-M1B, 2480B/ext-M1B, D62B/ext-M1B, G46B/ext-M1B, and
      G683B/ext-M1B expressed normal tillering in F1, and segregated into two different
      phenotypes of normal tillering type and excessive tillering type in a ratio of
      3:1 in F2. Inheritance analysis indicated that the excessive tillering character
      was controlled by a single recessive nucleic gene. By BSA (bulked segregants
      analysis) and microsatellite makers with the F2 population of 2480B/ext-M1B as
      the mapping population, RM197, RM584, and RM225, all of which were located on the
      short arm of rice chromosome 6, were identified to be linked with the excessive
      tillering gene with genetic distance of 3.8 cM, 5.1 cM, and 5.2 cM, respectively.
      This gene is probably a new excessive tillering gene in rice and is designated
      tentatively ext-M1B (t).

PMID- 16625833
TI  - Analysis of microsatellites in citrus unigenes.
AB  - Simple sequence repeats (SSRs) were investigated in the unigene sequences from
      expressed sequence tags (EST) of sweet orange (Citrus sinensis osbeck),
      trifoliate orange (Poncirus trifoliata Raf.) and other citrus species and
      cultivars. A total of 37 802 citrus unigene sequences corresponding to 23.29 Mb
      were searched, resulting in the identification of 8,218 SSRs. Among them there
      were 4,913 (59.8%) mono-, 1,419 (17.3%) di-, 1,709 (20.8%) tri-, 114 (1.39%)
      tetra-, 23 (0.28%) penta- and 40 (0.49%) hexa-nucleotide SSRs. The estimated
      frequency of SSRs was approximately 1/2.8 kb, which could be extrapolated to 1
      SSR-containing unigene in 4.6 unigenes. The maximum length of the SSR ranged from
      40 to 105 bp depending on the repeating numbers of the motif in the SSR. The
      overall average length of SSRs was 20.9 bp. The frequencies of different SSR
      types (di-, tri-, tetra-, and penta-nucleotide repeats) were very similar between
      sweet orange and trifoliate orange. The mononucelotide repeats appeared to be the
      most abundant SSRs within sweet orange and trifoliate orange, followed by
      trimeric repeats. The adenine rich repeats such as A/T, AG, AT, AAG AAAT, AAAG,
      AAAT, AAAAG, AAAAT etc. were predominant in each type of SSRs (mono-, di-, tri-,
      tetra-, and penta-), whereas the C/G, CG, CCG repeats were less abundant. Twenty
      five primer pairs flanking EST-SSR loci were designed to detect the possible
      polymorphism of six citrus cultivars including sweet orange and trifoliate
      orange. The PCR result with all these 25 primer pairs revealed the existence of
      polymorphism within six citrus cultivars confirming that citrus EST database
      could be efficiently exploited for the development of gene-derived SSR markers.

PMID- 16625834
TI  - Polymorphism of SARS-CoV genomes.
AB  - In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV)
      genome BJ202 (AY864806) was completely sequenced. The genome was directly
      accessed from the stool sample of a patient in Beijing. Comparative genomics
      methods were used to analyze the sequence variations of 116 SARS-CoV genomes
      (including BJ202) available in the NCBI GenBank. With the genome sequence of GZ02
      as the reference, there were 41 polymorphic sites identified in BJ202 and a total
      of 278 polymorphic sites present in at least two of the 116 genomes. The
      distribution of the polymorphic sites was biased over the whole genome. Nearly
      half of the variations (50.4%, 140/278) clustered in the one third of the whole
      genome at the 3' end (19.0 kb-29.7 kb). Regions encoding Orf10-11, Orf3/4, E, M
      and S protein had the highest mutation rates. A total of 15 PCR products (about
      6.0 kb of the genome) including 11 fragments containing 12 known polymorphic
      sites and 4 fragments without identified polymorphic sites were cloned and
      sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13
      804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and
      27 243) all contained 2 kinds of nucleotides. It is interesting to find that
      position 18379 which has not been identified to be polymorphic in any of the
      other 115 published SARS-CoV genomes is actually a polymorphic site. The
      nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV
      genomes, 18 types of deletions and 2 insertions were identified. Most of them
      were related to a 300 bp region (27,700-28,000) which encodes parts of the
      putative ORF9 and ORF10-11. A phylogenetic tree illustrating the divergence of
      whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also
      constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.

PMID- 16625835
TI  - Cloning, sequencing and analysis of the 16S-23S rDNA intergenic spacers (IGSs) of
      two strains of Vibrio vulnificus.
AB  - According to the conserved sequences flanking the 3' end of the 16S and the 5'
      end of the 23S rDNAs, PCR primers were designed, and the 16S-23S rDNA intergenic
      spacers (IGSs) of two strains of Vibrio vulnificus were amplified by PCR and
      cloned into pGEM-T vector. Different clones were selected to be sequenced and the
      sequences were analyzed with BLAST and the software DNAstar. Analyses of the IGS
      sequences suggested that the strain ZSU006 contains five types of polymorphic 16S
      23S rDNA intergenic spacers, namely, IGSGLAV, IGSGLV, IGSIA, IGSG and IGSA; while
      the strain CG021 has the same types of IGSs except lacking IGSA. Among these five
      IGS types, IGSGLAV is the biggest type, including the gene cluster of tRNAGlu
      tRNALys-tRNAAla-tRNAVal; IGSGLV includes that of tRNAGlu-tRNALys-tRNAVal; IGSAG,
      tRNAAla-tRNAGlu; IGSIA, tRNAIle-tRNAAla; IGSG, tRNAGlu and IGSA, tRNAAla.
      Intraspecies multiple alignment of all the IGS sequences of these two strains
      with those of V. vulnificus ATCC27562 available at GenBank revealed several
      highly conserved sequence blocks in the non- coding regions flanking the tRNA
      genes within all of strains, most notably the first 40 and last 200 nucleotides,
      which can be targeted to design species-specific PCR primers or detection probes.
      The structural variations of the 16S-23S rDNA intergenic spacers lay a foundation
      for developing diagnostic methods for V. vulnificus.

PMID- 16625836
TI  - Effects of degU32(Hy), degQa and degR pleiotropic regulatory genes on the growth
      and protease fermentation of Bacillus subtilis Ki-2-132.
AB  - Effects of degU32 (Hy), degR genes from Bacillus subtilis 168 and degQa gene from
      Bacillus amyloliquefaciens on Bacillus subtilis Ki-2-132 cell growth, sporulation
      and protease fermentation were investigated by introducing these genes into B.
      subtilis Ki-2-132 chromosome and/or cytoplasm. Although the genes come from
      different species and strains, they showed pleiotropic effects in B. subtilis Ki
      2-132. B. subtilis Ki-2-132degU32 (Hy) showed increased protease production, and
      when cooperating with degQa either in plasmid or in chromosome, further altered
      cell growth, increased protease production and affected the spore formation in a
      glucose and dosage dependent manner. By contrast, degR did not significantly
      affect the protease productivity in degU32 (Hy) mutant, consisting with that DegR
      was used to stabilise DegU-phosphate, which in degU32 (Hy) strain no longer
      further amplify the DegU-phosphate effect.

PMID- 16625837
TI  - The history of somatostatin analogs.
AB  - In the middle of the last century, there was a spectacular progress in the
      discovery, characterization and synthesis of neuropeptides. This was only
      possible because increasingly sophisticated analytical and isolation technology
      was becoming available. The pituitary lobes have become a real treasure house for
      the detection of different peptides, but also other glands and organs in the
      gastrointestinal (GI) and central nervous system (CNS) tracts have contained an
      ever growing list of regulatory peptides with sometimes unknown functionality.
      The main burning issues were to elucidate their role in physiology and, case by
      case and based on their structure, whether it was possible to design useful drugs
      for human therapy. Both issues were and are still being dealt with, and the
      history of somatostatin and somatostatin analogs is a good example of how such
      issues are being tackled successfully. In 1973, Brazeau and Guillemin's search at
      the Salk Institute for a GHRH in extracts of thousands of sheep hypothalami was
      crowned by a surprise, the discovery of a GHRH antagonist, a 14-amino acid Cystin
      bridge-containing peptide which they called somatostatin. This neuropetide
      appeared to be widely distributed in animal and human organs in the periphery and
      CNS, suggesting its potential regulatory functions, yet a thorough
      characterization of its properties due to its extremely short half-life was not
      possible. More insight could only be feasible with the synthesis of stable and
      potent analogs, a program that soon started in different research centers around
      the world. After having elucidated the 3-dimensional structure, the enzymatic
      degradation pattern and minimal chain length for biological activity of the
      natural hormone, the synthesis of a large number of analogs was started as early
      as 1974. The approach of the Sandoz team was to start with a hexapeptide lead
      structure Cys-Phe-DTrp-Lys-Thr-Cys and, by systematic elongation of the N and C
      terminals, in 1980 they managed to characterize the most stable and active analog
      with the following structure: H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr-OI-Octreotide.
      It was more potent in inhibiting GH in vivo compared to the native hormone. It
      demonstrated sufficient stability in vivo and, therefore, it was selected for
      clinical studies. In 1988, the first registration was obtained for treating
      acromegaly and carcinoid tumors. Since then, different depot preparations have
      been made available. Other analogs with similar structures have been also
      synthesized and are commercially available. The so-called targeting approach
      takes advantage of the presence of somatostatin receptors on different tumors. By
      coupling octreotide structural elements to so-called cage molecules complexing B
      or Y emitting isotopes, also the detection of somatostatin receptor containing
      tumors could be visualized and treated. The use of different somatostatin
      derivatives found its way since then both in basic research and in human therapy,
      and it is still opening new and exciting prospects.

PMID- 16625838
TI  - Physiology of somatostatin receptors.
AB  - Since its discovery three decades ago as an inhibitor of GH release from the
      pituitary gland, somatostatin has attracted much attention because of its
      functional role in the regulation of a wide variety of physiological functions in
      the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney
      and immune system. Its actions include inhibition of endocrine and exocrine
      secretions, modulation of neurotransmission, motor and cognitive functions,
      inhibition of intestinal motility, absorption of nutrients and ions and vascular
      contractility. In addition, the peptide controls the proliferation of normal and
      tumor cells. Its action is mediated by a family of G protein-coupled receptors
      [somatostatin receptor (SSTR)1-SSTR5] that are widely distributed in normal and
      cancer cells. Direct antitumor activities, mediated through SSTR expressed in
      tumor cells, include blockade of autocrine/paracrine growth-promoting hormone and
      growth factor production, inhibition of growth factor-mediated mitogenic signals
      and induction of apoptosis. Indirect antitumor effects include inhibition of
      growth-promoting hormone and growth factor secretion, and antiangiogenic actions.
      Many human tumors express more than one SSTR subtype, with SSTR2 being
      predominant. These receptors represent the molecular basis for the clinical use
      of somatostatin analogs in the treatment of endocrine tumors and their in vivo
      localization. This review covers the present knowledge in SSTR biology and
      signaling.

PMID- 16625839
TI  - Cortistatin: a natural somatostatin analog.
AB  - Cortistatin (CST) is a recently discovered neuropeptide from the somatostatin
      gene family named after its predominantly cortical expression and ability to
      depress cortical activity. CST shows many remarkable structural and functional
      similarities to its related neuropeptide somatostatin. However, the many
      physiological differences between CST and somatostatin are just as remarkable as
      the similarities. CST-14 shares 11 of its 14 amino acids with somatostatin-14,
      including the FWKT tetramer thought to be responsible for somatostatin's receptor
      interactions and the pair of cysteine residues that likely render the peptides
      cyclic. Yet the nucleotide sequences and chromosomal localizations of these genes
      clearly indicate they are products of separate genes and CST's activity in the
      brain is widely distinct from that of somatostatin. Now cloned from human, mouse
      and rat sources, in vitro assays show that CST is able to bind all five cloned
      somatostatin receptors and shares many pharmacological and functional properties
      with somatostatin, including the depression of neuronal activity and inhibition
      of GH release. However, distinct from somatostatin, CST has been shown to induce
      slow-wave sleep, reduce locomotor activity, and activate cation selective
      currents not responsive to, or antagonized by, somatostatin. Here we address the
      discovery and characterization of this novel somatostatin-like neuropeptide,
      including its cloning, expression and pharmacology. We also examine the evidence
      pointing towards a specific receptor for this novel neuropeptide member of the
      somatostatin gene family.

PMID- 16625840
TI  - Medicinal chemistry of somatostatin analogs leading to the DTPA and DOTA
      conjugates of the multi-receptor-ligand SOM230.
AB  - The somatostatin field has been a success story in terms of medicinal chemistry
      and drug discovery offering a variety of therapeutic opportunities. A rational
      medicinal chemistry approach capitalising on structure activity relationships has
      led to the discovery of SOM230, a novel, stable cyclohexapeptide somatostatin
      analog which exhibits multi-receptor binding to human somatostatin receptor
      (SSTR) subtypes (SSTR 1-5). Recently, we extended this research utilising the
      hydroxproline urethane extension of SOM230 for the attachment of the chelators
      DTPA and DOTA, which enable early diagnosis of SSTR positive tumors and
      radiotherapy.

PMID- 16625841
TI  - BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine
      receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary
      adenomas partial responders to octreotide.
AB  - We report the comparative efficacy of a somatostatin receptor 1 and 5 subtypes
      (SSTR2 and SSTR5), and dopamine D2 (DAD2) compound, BIM-23A760, in suppressing GH
      secretion, in cell culture from human GH-secreting tumors, from patients
      partially responsive to long-term treatments with octreotide or lanreotide. In 18
      tumors tested, the SSTR2, SSTR5, and DAD2 mRNAs were coexpressed. The SSTR2
      selective analog, BIM-23197, the SSTR5-selective analog, BIM-23268, and the
      dopamine (DA) analog, BIM-53097, produced a mean maximal suppression of GH
      secretion (24 +/- 3, 20 +/- 3, and 20 +/- 3%, respectively) that was similar to
      that obtained with octreotide (23 +/- 3%). Nevertheless, based on individual
      responses, 60% of the tumors were mostly sensitive to the SSTR2 analog while 19
      and 21% of the tumors were mainly responsive to the SSTR5 analog and to the DA
      analog, respectively. Among a series of new chimeric compounds that bind the
      SSTR2, SSTR5, and DAD2 receptors with variable affinities, BIM-23A760 produced
      greater maximal suppression of GH secretion than octreotide (38 +/- 2 vs 24 +/-
      2%; p<0.03). The EC50 for BIM-23A760 was 2 pmol/l. In the presence of sulpride,
      the dose response inhibition of GH secretion by the trihybrid molecule, BIM
      23A760, was partially reversed. The trihybrid produced also a maximal suppression
      of PRL greater than octreotide (74 +/- 5 vs 46 +/- 11%). When SSTRs pan
      inhibitors such as BIM-23A779 (binding affinity for SSTR1, SSTR2, SSTR3, SSTR5,
      respectively: 2.5, 0.3, 0.6, 0.6 nmol/l) or SOM230 were tested for their
      suppressive effects on GH secretion, they were less potent than the previous
      dopastatin hybrid molecule. After a brief exposure to a SSTR2-selective analog,
      BIM-23197, or to a DA analog, BIM-53097, the maximal GH suppression was achieved
      during 12 h. Under exposure to BIM-23A760, in the same conditions, maximal
      suppression of GH secretion lasted for 24 h. Such a longer biological effect, yet
      not explained, probably participates in the higher efficacy of BIM-23A760. The
      higher efficacy of BIM-23A760 is, at least partially, linked to its high affinity
      for the SSTR2 receptor subtype (IC50: 3 pmol/l). As compared to the dopastatin
      compound, the lower efficacy of the universal somatostatin ligands in the
      inhibition of GH secretion of GH-secreting tumors argues for the use of drugs
      targeted, according to specific receptors expression and functionality which may
      vary among the various classes of tumors.

PMID- 16625842
TI  - Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH,
      corticosterone and ghrelin in rats.
AB  - SOM230 is a novel somatostatin analog which shows affinity to 4 of the 5 known
      somatostatin receptors (SSTR1-5). In binding experiments, SOM230 has a higher
      affinity to SSTR1, SSTR3 and SSTR5 and a slightly lower affinity to SSTR2
      compared to octreotide. In addition, SOM230 has a >7-fold longer plasma half-life
      than octreotide (11 vs 1.5 h). It was suggested that SOM230 with its broader
      binding and activity profile compared to octreotide should have a stronger
      (usually inhibitory) effect on the secretion of hormones. In several animal
      species, SOM230 was a more potent inhibitor of GH and IGF-I than octreotide. This
      is in line with a strong expression of both SSTR2 and SSTR5. In the pituitary of
      patients with primary Cushing's disease, the SSTR5 is more frequently expressed
      than SSTR2. Accordingly, in rats SOM230 caused a stronger inhibition of ACTH and
      corticosterone secretion than octreotide. In contrast, most recent experiments
      showed that octreotide was more potent than SOM230 to inhibit ghrelin secretion
      in rats. This effect could be explained by the strong expression of SSTR2 in the
      rat stomach, whereas expression of SSTR3, SSTR4 and SSTR5 was poor or absent.
      Based on these data it can be concluded that in tissues (or tumors), where
      several SSTRs are expressed, SOM230 will generally have a stronger effect than
      octreotide. In cases where SSTR2 is the most important receptor mediating a
      response (e.g. ghrelin release in rats), the stronger inhibitory effect of
      octreotide can be explained by its higher affinity for SSTR2. In contrast to the
      long-lasting inhibitory effect of SOM230 on GH and IGF-I secretion, the
      inhibitory effects of both compounds on ghrelin show strong tachyphylaxis. These
      data are in line with the hypothesis that activation of the SSTR2 alone results
      in a rapid desensitization of the response. If, however, additional SSTR subtypes
      (especially SSTR5) are expressed and activated by multiligand analogs like
      SOM230, this might not only form the basis for a stronger response, but also the
      basis for a reduced tachyphylaxis.

PMID- 16625843
TI  - Pre-clinical and clinical experiences with novel somatostatin ligands:
      advantages, disadvantages and new prospects.
AB  - Since the cloning and characterization of the five human somatostatin receptor
      (SSTR) subtypes, our understanding of the expression and functional role of the
      five SSTR subtypes in human (neuro-)endocrine tumors has increased significantly.
      The majority of human (neuro-)endocrine tumors express multiple SSTR. GH
      secreting pituitary adenomas preferentially express SSTR2 and SSTR5,
      prolactinomas SSTR1 and SSTR5, and corticotroph adenomas express SSTR2 (low
      number) and predominantly SSTR5s. In addition, gastroenteropancreatic (GEP)
      neuroendocrine tumors frequently express multiple SSTR as well, with SSTR2 being
      expressed at the highest level. Treatment with the current generation of
      octapeptide somatostatin-analogs, e.g. octreotide and lanreotide, normalizes
      circulating GH- and IGF-I levels in approximately 60-70% of acromegalic patients,
      thereby remaining about one-third of patients uncontrolled. In patients with GEP
      neuroendocrine tumors, both somatostatin-analogs effectively suppress the
      production of bioactive peptides and hormones by the tumor cells, resulting in an
      important improvement of the related clinical symptomatology. However, a
      considerable proportion of patients experience an escape from treatment within
      months to several years. Altogether, the current generation of somatostatin
      analogs are effective medical tools in the treatment of acromegalic patients and
      of patients with neuroendocrine GEP tumors, but there is certainly a need for
      novel somatostatin analogs. In recent years, a significant number of novel
      somatostatin-ligands has been developed. These ligands include SSTR selective-,
      bi-specific, universal, as well as chimeric dopamine (DA)-somatostatin ligands.
      In vitro studies using human pituitary adenoma cells demonstrate a more profound
      inhibition of GH, PRL and ACTH secretion by somatostatin-analogs targeting both
      SSTR2s and SSTR5s, compared with SSTR2-preferential somatostatin-analogs. This
      likely reflects the SSTR subtype expression pattern in the adenoma cells. A first
      proof-of-concept trial with the more universal somatostatin-ligand SOM230 in 12
      acromegalic patients shows that a single dose of SOM230 is effective in
      suppressing circulating GH concentrations in a significant larger number of
      patients compared with octreotide. In animal models, SOM230 has a better effect
      on GH and IGF-I level with less signs of tachyphylaxis compared with octreotide.
      Depending on the SSTR expression pattern on neuroendocrine GEP tumors,
      somatostatin-analogs targeting multiple SSTRs may play a future role in the more
      long-term control of patients with neuroendocrine GEP tumors. The first clinical
      trial comparing octreotide and SOM230 is ongoing. However, every advantage has
      its disadvantage. Targeting multiple SSTR potentially induces more adverse
      effects as well. Especially, glucose homeostasis might induce new problems in the
      long-term use of universal ligands.

PMID- 16625844
TI  - Diagnosis and treatment of acromegaly and its complications: consensus
      guidelines.
AB  - In February 1999, May 2000 and April 2002, three workshops were held in Cortina,
      Montecarlo and Versailles, respectively, to develop a consensus defining the
      diagnosis and treatment of acromegaly and its complications. The workshops were
      sponsored by the Pituitary Society and European Neuroendocrine Association.
      Invited international participants included endocrinologists, neurosurgeons and
      radiotherapists skilled in the management of acromegaly. This review paper
      summarizes the main points of the three consensus statements published following
      these three workshops.

PMID- 16625845
TI  - Can treatment with somatostatin analogs replace neurosurgery?
AB  - There is an ongoing controversy on first-line treatment in acromegaly. Although
      transsphenoidal surgery has always traditionally been considered the first
      option, the evolution of new medical treatments is now challenging the clinical
      paradigm. In fact, somatostatin analogs are highly effective, convenient, avoid
      the growth of tumors or even shrink them, and also have the advantage of
      preserving normal pituitary function. On the other hand, when successful,
      neurosurgery has the advantage of eliminating long-term medical treatment and is
      less expensive. This manuscript discusses the pros and cons of both treatments.

PMID- 16625846
TI  - Efficacy and limits of somatostatin analogs.
AB  - For a considerable time, somatostatin analogs have been the medical therapy of
      choice for the treatment of acromegaly. In addition to their well-established use
      as an adjunctive therapy, primary therapy with somatostatin analogs has been
      investigated in recent years. Adjunctive therapy with octreotide long-acting
      release over 12-36 months allowed for sufficient GH suppression in 47-75% of
      patients (average 56%), as summarized by Freda. IGF-I was normalized in 41-75%
      (average 66%). Tumor shrinkage was observed in about 30% of patients, with a mass
      reduction of 20-50% in most cases. A bias in some of these studies cannot be
      excluded, with patients being selected on base of their octreotide
      responsiveness. Regarding primary treatment of acromegaly with long-acting
      somatostatin analogs, our review of five published studies, that applied
      stringent criteria for the analysis of biochemical normalization, revealed
      sufficient GH and IGF-I suppression in 68% and 61% of the 107 patients included,
      respectively, and significant tumor reduction in 51%. Therefore, somatostatin
      analogs represent an effective medical therapy in a significant proportion of
      patients with acromegaly. Resistance to currently available somatostatin analogs
      in some patients may be due to reduced density of SSTR2 on the tumors of these
      patients. New somatostatin receptor ligands with extended binding profile may
      have even higher efficacy in the biochemical control of patients with acromegaly.

PMID- 16625847
TI  - New perspectives in the medical treatment of acromegaly.
AB  - Currently available medical treatment of acromegaly includes dopamine agonists,
      slow release formulation of somatostatin analogues and pegvisomant, a GH-receptor
      antagonist. Dopamine agonists are well tolerated, not expensive but poorly
      effective. Somatostatin analogues are highly effective in 60-70% of patients
      based on the receptor profile of individual tumors. Pegvisomant is reported to
      normalize IGF-I levels in nearly the totality of the patients, but is devoted of
      tumor shrinking effect. In a preliminary study in patients with acromegaly, a new
      somatostatin analogue with affinity to four of the five somatostatin receptors
      (SOM230) was shown to be similarly effective as octreotide in some patients and
      more effective than octreotide in other patients. Moreover, new molecules with
      selective activity on the somatostatin receptor type 2, or 5, or 1 have been
      reported in vitro to strongly suppress GH secretion. Other new promising
      alternatives are the chimeric compounds with both somatostatin receptor and
      dopamine receptor binding. These drugs have been also shown to possess strong GH
      inhibitory activity in primary cultures from GH-secreting adenomas. These drugs
      are the future perspectives in the treatment of patients with GH-secreting or
      GH/PRL-secreting tumors.

PMID- 16625848
TI  - An overview of the epidemiology and genetics of acromegaly.
AB  - Historical data indicate that pituitary tumors represent 10% of intracranial
      tumors, while adenomas are noted in approximately 14-23% of normal subjects on
      autopsy or magnetic resonance imaging (MRI). About 2.5% of these tumors stain
      positive for GH in histopathologic studies. In contrast, the prevalence of
      clinically diagnosed acromegaly is lower at 36-69 per million population. Ongoing
      studies indicate that the actual prevalence of acromegaly in the community may be
      higher than previous epidemiologic data suggest. Acromegaly can occur both
      sporadically and in the setting of familial conditions, such as multiple
      endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Isolated familial
      somatotropinoma has been described and newer data suggest that acromegaly may
      also occur in non-MEN1/CNC families in combination with other pituitary tumor
      phenotypes.

PMID- 16625849
TI  - Review of Cortina criteria for the diagnosis of acromegaly.
AB  - Diagnostic protocols for acromegaly have evolved over time reflecting the
      refinement of assays for the biochemical assessment of the GH-IGF-I axis and
      greater understanding of disease process. In February 1999, an International
      Consensus Conference was held in Cortina, Italy, to define the criteria for cure
      of acromegaly. This review paper summarizes the diagnostic guidelines proposed in
      the consensus statement by Giustina et al. In recent years, however, the criteria
      for both biochemical assessment and long-term monitoring in patients with
      acromegaly have changed with the development of increasingly sensitive and
      specific GH assays coupled with the widespread availability of reliable IGF-I
      assays. For this reason, constant updating of the assessment criteria proposed in
      the workshop held in Cortina, in 1999, would be advisable.

PMID- 16625850
TI  - Are there alternative tests for diagnosis of acromegaly?
AB  - In acromegaly, clinical features are of the utmost importance, and biochemical
      confirmation is rarely difficult. However, some clinically manifest acromegalics
      have subtle abnormalities in GH secretion resulting in post-glucose GH nadir in
      the designated "normal" range with high IGF-I levels. Clinical decision may be
      based on the probability of the disease and elevated IGF-I levels. The TRH test
      or the frequent GH sampling test may help confirm acromegaly but on their own
      have no diagnostic advantage. A TRH-GH response is not specific to acromegaly,
      while frequent sampling is not practical. Other tests rarely add information
      beyond that obtained by usual investigations. Post-treatment assessment of the
      disease activity and definition of acromegaly cure, by measuring GH secretion,
      remain problematic. IGF-I levels seem to differentiate normality less clearly and
      discordance of GH and IGF-I results is frequent. Post-treatment probability for
      residual disease activity should include more clinical parameters such as insulin
      sensitivity, leptin and echocardiography. Furthermore, with efforts to achieve
      tight biochemical control of the disease it is foreseeable that a proportion of
      patients may be rendered GH deficient, requiring stimulatory testing. Acromegaly
      is a disfiguring and disabling illness, in which by definition, the disorder is
      caused by a pituitary GH-secreting adenoma resulting in high circulating levels
      of GH and IGF-I. The clinical features of acromegaly include those of GH and IGF
      I on tissues and the effects of the pituitary tumor itself. There is no single
      cut-off value for GH with perfect discrimination between acromegaly and
      normality. The recommended post-glucose GH nadir value of 1 microg/l is now
      considered to be inappropriately high, and measurement of IGF-I levels although
      extremely valuable has its limitations. Furthermore, some acromegalics may have
      subtle abnormalities in GH secretion, resulting in post-glucose GH nadir in the
      designated "normal" range with elevated IGF-I levels.

PMID- 16625851
TI  - GH and mortality in acromegaly.
AB  - Effective biochemical control of GH and IGF-I levels in subjects with acromegaly
      can reduce mortality to that of the general population. Several retrospective
      studies have reported that the increased mortality is improved if GH levels are
      reduced to <2.5 microg/l, measured as mean of GH day profile or random GH level.
      It has been proposed that control or "cure" of disease is achieved when mean GH
      levels are <2.5 microg/l, nadir GH after an oral glucose load is <1 microg/l, and
      circulating IGF-I is reduced to an age- and sex-adjusted normal range. However,
      virtually all evidence from epidemiological studies has related GH values and not
      IGF-I values to long-term morbidity and mortality; controversy remains regarding
      the relative importance of these 2 parameters in determining post-treatment
      control status. Review of the West Midlands Acromegaly Database (419 patients)
      revealed that mortality was increased in the subgroup of patients with GH levels
      >2 microg/l (measured either as mean GH day profile or GH values across an oral
      glucose tolerance test, or random GH level). Factors influencing mortality in
      acromegaly were analyzed in a study from New Zealand of 208 acromegalic subjects.
      Serum GH at last follow-up was the most significant predictor of mortality, with
      mortality rates reduced to normal by achieving GH concentrations <1-2 microg/l. A
      nationwide survey of mortality in 334 patients with acromegaly from Finland has
      reported no difference in overall mortality between patients and general
      population; however, patients with last known basal serum GH >2.5 microg/l showed
      excess mortality (SMR 1.61, p<0.001). These 3 analyses of 961 patients indicate
      unequivocally that a GH value of 1-2 microg/l is an appropriate therapeutic
      target, as values above this level are associated with increased mortality.

PMID- 16625852
TI  - IGF-I and mortality in patients with acromegaly.
AB  - There are several studies in the literature relating mortality in patients with
      acromegaly to GH levels either as random samples or as a mean of several
      spontaneous samples or GH nadir after oral glucose load. Fewer articles have been
      published until now on the relationship between IGF-I and mortality, with several
      of these studies reporting a clear association, while two databases did not find
      an association between mortality and IGF and have instead shown an
      interrelationship between mortality and GH levels. These latter studies report
      databases in which fewer individuals have been sampled for IGF-I than for GH.
      Moreover, reliable immunoassays for GH measurement have existed for almost 20 yr
      more than immunoassays for IGF-I. Since between-method results diverge for both
      GH and IGF-I, it appears desirable to have levels of both biochemical markers
      measured in the follow-up of acromegaly, preferably in a central laboratory
      setting. Only by this prospective effort, it will be possible in the future to
      evaluate the relative ability of IGF-I and GH in predicting the residual risk of
      patients with acromegaly in relation to mortality, but also to co-morbidities.

PMID- 16625853
TI  - Biochemical evidence supporting the Cortina criteria.
AB  - Whether acromegaly is inactive or active, respectively cured or not cured depends
      on the GH suppressibility and the basal IGF-I level. According to the Cortina
      criteria, GH suppression after oral ingestion of 75 g glucose to <1 microg/l
      using conventional polyclonal immunoassays and an IGF-I level within the age
      matched normal range are regarded as evidence of good control of acromegaly.
      According to more recent publications, mortality, which is increased in active
      acromegaly, is normalized when GH and IGF-I levels have become normal as defined
      above. Morbidity, i.e. typical features of acromegaly like cardiac problems,
      carpal tunnel syndrome, carbohydrate intolerance, and excessive sweating may also
      improve though painful arthropathy, and coarse facial features usually remain
      unaltered even if the biochemistry has been completely normalized. Using more
      sensitive GH assays, a group of acromegalic patients was shown to have normal IGF
      I levels after surgery, with post-glucose levels of GH <1 microg/l but >0.14
      microg/l, which is the upper level of normal subjects and of a second group of
      successfully operated acromegalic patients. The latter group also had slightly
      lower IGF-I levels, though such levels were normal in both groups. Whether this
      may indicate that these patients who have higher GH levels after oral glucose
      measured with the more sensitive immunoradiometric assay (IRMA) will more likely
      develop recurrences remains to be demonstrated in a larger cohort. According to
      the criteria put forward in Cortina d'Ampezzo in February 1999, all patients who
      have post-glucose GH levels <1 microg/l and normal age-matched IGF-I levels have
      to be regarded as well controlled, i.e. sufficiently treated. Because of lack of
      evidence, there is at present no reason to change the consensus reached there.

PMID- 16625854
TI  - Biochemical evidence in favor of revising Cortina criteria.
AB  - There is evidence that the Cortina criteria for the cure of acromegaly are not
      strict enough if the aim is to predict patients where cure will be successful as
      opposed to patients who will suffer disease recurrence or will have mortality and
      morbidity return to disease-like levels. These criteria depend on biochemical
      measurements of GH and IGF-I that are not universally standardised or comparable,
      even when excluding the older, less sensitive polyclonal radio immuno assay
      (RIA). The biochemical evidence suggesting a revision of the criteria for curing
      acromegaly and derived proposals can be summarised as follows: A) Using
      immunoradiometric assay (IRMA) for GH measurement, no acromegalic patient with
      elevated IGF-I suppressed GH after 100 g oral glucose tolerance test (OGTT) to <
      or = 0.14 microg/l, but 50% suppressed to <1microg/l. B) With hourly GH
      measurements using IRMA, cured acromegalic patients exhibit basal GH values < or
      = 0.33 microg/l (x +/- 2 SD). C) In patients with normal IGF-I having GH after
      OGTT suppressed to < or = 0.14microg/l no recurrences were observed, while in 19%
      with GH >0.14 microg/ showed recurrences (4, 5); however, this was not the
      experience of others. D) Polyclonal assays for GH exhibit overlap of GH
      suppression after OGTT between normal subjects and active patients and should
      therefore be avoided. E) A recent agreement for implementing universal rhGH
      reference standards by September 2006 will hopefully facilitate the comparison of
      different assays in the future. F) Reliable IGF-I assays require age- and sex
      matched reference ranges. G) For evaluation of long-term biochemical assessment
      after treatment, both GH and IGF-I should be undertaken. H) In order to monitor
      treatment with GH-receptor antagonists, a reliable IGF-I assay is of critical
      importance, since GH measurements cannot be used to evaluate treatment efficacy.

PMID- 16625855
TI  - Novel molecular aspects of pituitary adenomas.
AB  - Ghrelin stimulates while somatostatin inhibits GH release and they thus serve as
      functional antagonists. We have compared their effects on cell proliferation.
      Ghrelin stimulates while somatostatin inhibits cell proliferation in most tissues
      and cell lines. Here we show that ghrelin and desoctanoyl ghrelin stimulate cell
      proliferation in rat pituitary cell line (GH3), and these effects could be
      inhibited with mitogen-activated protein kinase (MAPK), tyrosine kinase and
      protein kinase C inhibitors. Somatostatin and its analogs negatively regulate the
      growth of pituitary cells, and we now show that they inhibit MAPK activation. We
      hypothesised that one of the mechanisms involved in the somatostatin effect is a
      stimulation of cell cycle inhibitor p27, as pituitary adenomas have decreased p27
      peptide content. Both octreotide and a new somatostatin analog SOM230 treatment
      resulted in an upregulation of p27 protein levels in human somatotrophinoma
      cells. In summary, we suggest that ghrelin and somatostatin have opposite effects
      on somatotroph cells not just at the level of GH release but also in terms of
      cell proliferation. Ghrelin may play a role in pituitary tumorigenesis via an
      autocrine/paracrine pathway. Our results also suggest that the antiproliferative
      effect of somatostatin analogs octreotide and SOM230 involve the up-regulation of
      p27 and down-regulation of the MAPK pathway in human somatotrophinomas.

PMID- 16625856
TI  - Non-functioning pituitary adenomas.
AB  - The vast majority (>80%) of clinically non-functioning pituitary adenomas (NFPAs)
      are gonadotroph-cell adenomas, as demonstrated by immunocytochemistry. However,
      they are rarely associated with increased levels of dimeric LH or FSH. Increased
      levels of uncombined subunits (free alpha-subunit mainly, LH-beta subunit more
      rarely) are more frequently encountered, but are generally modest. The main
      problems raised by NFPA are mass effects problems, responsible for optic chiasm
      compression or deficient hormone secretion resulting from compression of normal
      anterior pituitary cells. The therapeutic management of NFPA may require
      combination of different options. The strategy of observation only for patients
      with incidentally discovered pituitary adenomas may be appropriate, provided that
      the tumor is well-delimited, small, has no extension with risk of neurological or
      visual chiasm compression, and that a meticulous hormonal work-up has ruled out
      the possibility of a minimal hormonal hypersecretion. Transsphenoidal surgery
      allows improvement in visual disturbances due to chiasmal syndrome in most
      patients, and sometimes, in pituitary function. After surgery alone, nearly 30%
      (between 10 and 69%, according to the series) of patients relapse within 5 to 10
      yr. Radiotherapy is proposed either as a systematic adjunct or only if a
      significant remnant persists. Systematic radiation therapy is supported by the
      low relapse rate (mean, 11%; range, 6-21%) observed when radiation therapy is
      systematically associated with surgery. However, irradiation is almost always
      followed by hypopituitarism which might be associated with a reduction in life
      expectancy, despite appropriate replacement therapy. Results of medical treatment
      are disappointing. Dopamine agonist bromocriptine decreases gonadotropin and
      alpha-subunit in vitro and in vivo, but, in clinical studies, was poorly
      effective in reducing supranormal gonadotropins and free subunits levels, and
      rarely produced a minimal tumoral shrinkage. Cabergoline may be more efficacious.
      Somatostatin analogs are able to improve minimally visual problems in 20-40% of
      cases, but reduction in tumoral volume is anecdotic. Whether new somatostatin
      analogs (e.g. SOM230 which is a multiligand agonist) will improve these results
      is presently unknown. Administration of GnRH agonists is generally ineffective
      and may be hazardous. Prolonged administration of GnRH antagonist in a small
      number of patients with a secreting gonadotroph cell adenoma has been reported to
      reduce supranormal gonadotropins levels but not to produce any change in tumoral
      size.

PMID- 16625857
TI  - Pathophysiology of pituitary adenomas.
AB  - Pituitary tumor initiation and progression are associated with a plethora of
      genetic imbalances. The role of pituitary trophic status as determinant of
      neoplastic potential is not clear. The pituitary gland responds to diverse
      central and peripheral signals by undergoing reversible plastic and functional
      changes. The resulting hyperplasia/excess hormone production, or
      involution/hyposecretion in pituitary cells may correlate with the ability to
      develop pituitary tumors. It is difficult to test this hypothesis, in part due to
      limitations on the definition of human pituitary cell trophic status and because
      this organ is not readily accessible for serial histopathological analysis.
      Therefore, animal models represent the most functional approach to testing this
      hypothesis. Transgenic mouse models of pituitary tumor transforming gene (PTTG)
      inactivation or overexpression support the notion that a permissive trophic
      environment may be required for pituitary tumor formation. Mechanisms underlying
      changes in pituitary plasticity and their relationship to tumor development may
      account for the diverse genetic abnormalities observed in pituitary tumors.

PMID- 16625858
TI  - Potential indications for somatostatin analogs in Cushing's syndrome.
AB  - In recent years, somatostatin analogs have been proposed and used in the
      diagnosis and therapy in Cushing's syndrome (CS). In these last few years, the
      potential therapeutic effects of somatostain analogs have been studied in
      different aspects of CS. The strong expression of somatostatin receptors (SSTR)
      type 5 in human corticotroph cells and the demonstrated efficacy of SOM230, a
      novel multi-ligand somatostatin analog, in inhibiting ACTH release in vitro
      suggest that this new drug may be effective in the treatment of ACTH
      hypersecretion. Very preliminary in vivo results suggest that SOM230 could be a
      promising drug in medical therapy for patients with Cushing's disease (CD).
      Prolonged treatment and more data will be needed in order to evaluate its long
      term therapeutic efficacy.

PMID- 16625859
TI  - Potential indications for somatostatin analogues: immune system and
      limphoproliferative disorders.
AB  - Among hormones and neuropeptides influencing the immune system, somatostatin
      seems to play a key role not only in inhibiting specific immune cell activities,
      but also in promoting selected functions of particular immune cell subsets.
      Indeed, controversial effects have been observed in experimental conditions where
      somatostatin seems to stimulate certain cell functions, such as secretion of
      specific products (immunoglobulin, cytokines), cell migration and adhesion to
      extracellular matrix components. However, interestingly, cortistatin (CST), a
      neuropeptide that strongly resembles somatostatin, from both the structural and
      functional points of view, seems to have potential roles in regulating immune
      responses, as well as other lymphoid cell functions. The unexpected wide
      distribution of CST in a number of human organs, but particularly in immune
      cells, points to a broader physiological role of CST than previously presumed.
      The actions of somatostatin and its synthetic analogs (SSA) are mediated by five
      membrane G protein-coupled receptors subtypes (SSTR1-5), displaying a tissue
      specific distribution. The majority of somatostatin-target tissues, including
      lymphoid tissues, may co-express multiple somatostatin receptor (SSTR). The
      number of SSTRs in lymphoid cells is significantly lower compared to
      neuroendocrine tissues. However, the presence of receptors allowed the
      localization by in vivo SSTR scintigraphy of lymphoproliferative disorders, as
      well as granulomatous and autoimmune diseases. In specific cases, this technique
      may contribute to establishing the diagnosis and staging the disease. Recent
      studies evaluating the specific and quantitative SSTR distribution in lymphoid
      organs and cells, in both normal conditions and immune disorders, have largely
      contributed to better understand the phenomenology of in vivo receptor imaging
      and also the involvement of the different SSTR in determining the uptake of
      radiolabeled SSAs. Moreover, since lymphomas are highly radiosensitive
      malignancies, a promising approach in refractory patients with malignant
      lymphomas may be represented by radionuclide-targeted therapy with radioactive
      coupled SSAs combined with gene therapy. This latter technique seems effective in
      inducing the expression or increasing the number of given SSTR in order to
      ameliorate the impact of radionuclide-targeted therapy. Medical treatment of
      lymphoproliferative diseases with currently available synthetic analogs have
      produced unsatisfactory and conflicting results. This might be due to the
      affinity of the current available SSAs for specific SSTR. However, the synthesis
      of new compounds with distinct properties has reopened a challenge in this field.
      The application of receptor-based localization and anti-tumor strategies should
      also be taking into account the new knowledge recently emerged on the
      physiopathology of neuropeptide receptors: firstly, neuropeptide receptor homo-
      and heterodimerization, which may involve different subtypes of SSTRs, as well as
      other neuropetide receptors, and secondly, the role of endogenous SSTR ligands,
      such as CST.

PMID- 16625860
TI  - Somatostatin-related therapeutics in ophthalmology: a review.
AB  - Somatostatin and its derivatives have been predominantly studied and succesfully
      used in endocrinological diseases. This article reviews the rationale of the use
      of somatostatin and its derivatives in ophthalmology based on current
      understanding of its action in the eye and summarizes previously published
      controlled studies and case series. The article points out future possible
      applications. Larger randomised controlled studies are necessary to confirm its
      current and future use. New ways of application could facilitate its broader use
      in ophthalmology.

PMID- 16625861
TI  - Somatostatin, cortistatin, ghrelin and glucose metabolism.
AB  - At first sight, the title is confusing as it seems to try to merge four unrelated
      topics into a single presentation. Somatostatin, cortistatin (CST) and ghrelin
      display broad biological activities, including metabolic effects. However,
      although apparently unrelated, these peptides entities have more in common than
      it might be expected and their reciprocal interactions give a new perspective to
      the hormonal regulation of glucose metabolism. Let's analyze the ghrelin receptor
      subtype GH secretagogue (GHS)-receptor 1a (R1a). Taking into account the GHS-R1a
      as receptor of reference, acylated ghrelin is one of its natural ligands.
      Interestingly, it has been demonstrated that also CST, a neuropeptide, binds with
      high affinity to the GHS-R1a in human hypothalamus and pituitary tissues. CST is
      a recently described neuropeptide showing high structural homology with
      somatostatin that binds to all somatostatin receptor subtypes (SSTRs) with an
      affinity (1-2 nM). In fact, CST and somatostatin exhibit the same endocrine
      activities. The existence of specific receptors which selectively bind
      somatostatin or CST has been hypothesized, based on evidence that CST possesses
      an action profile different from somatostatin and that CST and somatostatin are
      often co-expressed in the same neurons but are regulated by different stimuli.
      Given these findings, the ability of CST to bind the GHS-R1a is of particular
      relevance because somatostatin and its fragments do not bind the same receptor.
      Interestingly, the classical synthetic somatostatin analogs, i.e. octreotide,
      lanreotide and vapreotide bind the GHS-R1a with an affinity lower than that of
      CST. These findings have generated the hypothesis that CST, because of its
      ability to bind both SSTRs and GHSRs, would represent the link between ghrelin
      and "somatostatin/CST" system that had not previously been demonstrated. On the
      other hand, the GHS-R1a is unlikely to be the only GHS-R. It has been already
      demonstrated that a GHS-R subtype able to bind non-acylated as well as acylated
      ghrelin exists and likely mediates biological activities. Another GHS-R subtype
      likely mediates the influence of unacylated ghrelin on glucose metabolism, since
      it does not bind nor activates the GHS-R1a. Given this complexity, it is clear
      that further studies are required to clarify whether ghrelin is the sole ligand
      or one of a number of ligands activating the GHS-R 1a and whether that receptor
      used for ghrelin isolation is the sole receptor or one of a group of receptors
      for such ligands.

PMID- 16625862
TI  - Neuroendocrine tumors and somatostatin: imaging techniques.
AB  - Tumors and metastases bearing the somatostatin receptor subtypes 2 (SSTR2) or
      SSTR5 can be visualized in vivo after injection of radiolabeled octapeptide
      somatostatin analogs like 111In-pentetreotide. The sensitivity of 111In
      pentetreotide scintigraphy for the detection of carcinoid tumors is 86-95%. The
      sensitivity of 111In-pentetreotide scintigraphy for the detection of gastrinomas,
      vasoactive intestinal polypeptide-secreting tumors, and glucagonomas as well as
      clinically non-functioning lesions is 75-100%. However, for insulinoma this is 50
      60%. 111In-pentetreotide scintigraphy generally has a lower detection rate for
      benign pheochromocytomas than 123I-MIBG scintigraphy, but it can have a
      complementary role for the staging of malignant pheochromocytomas. It can also be
      used for the detection of extra-adrenal pheochromocytomas and paragangliomas.
      Most GH- and TSH-secreting pituitary adenomas can be visualized using 111In
      pentetreotide. 111In-pentetreotide scintigraphy is negative in microprolactinomas
      and ACTH-secreting pituitary microadenomas. 111In-pentetreotide scintigraphy has
      been successful for the localization of extra-pituitary ACTH-secreting tumors and
      their metastases, and especially for occult tumors. A large variety of lesions in
      and around the pituitary region express somatostatin receptors and, therefore,
      can be visualized by 111In-pentetreotide scintigraphy.

PMID- 16625863
TI  - Somatostatin analogs in the treatment of neuroendocrine gastroenteropancreatic
      and intrathoracic tumors.
AB  - Somatostatin is a peptide hormone that posses several biological functions of
      which inhibition of hormone secretion from endocrine cells is one. Neuroendocrine
      tumors usually express somatostatin receptors (SSTRs), although the subtypes and
      number of SSTRs expressed in a certain tumor is very variable. The primary goal
      of somatostatin analog treatment is to decrease hormone production and secretion,
      resulting in control of hormone induced symptoms, while the ability of
      somatostatin analogs to retard tumor growth is less well documented. All patients
      considered for somatostatin analog treatment should undergo SSTR scintigraphy
      (111In-pentetreotide) to establish SSTR status, since the expression is usually
      correlated to therapeutic response. By this approach, it is possible to select
      patients suitable for treatment. Among patients with functioning neuroendocrine
      tumors expressing SSTR, more than 80% respond with symptomatic relief during
      somatostatin analog treatment, while treatment of non-functioning tumors still
      remains somewhat controversial.

PMID- 16625864
TI  - The neuroendocrine phenotype in prostate cancer: basic and clinical aspects.
AB  - Most of the conventional adenocarcinomas of the prostate display focal
      neuroendocrine (NE) differentiation at diagnosis, usually revealed by
      immunohistochemistry as solitary or clusters of cells, in the context of
      predominantly exocrine tumors. Even though the biological and clinical
      significance of NE differentiation in prostate cancer is still to be elucidated,
      NE phenotype is emerging as an important factor in the prognosis, evolution and
      progression of prostate cancer. It seems to be particularly relevant in
      facilitating prostate cancer progression during the ordinary androgen-suppression
      therapy (LHRH-analogs +/- anti-androgens). Several mechanisms have been
      identified: NE cells are androgen receptor negative, therefore they survive to
      androgen deprivation; NE cells produce peptides, hormones and growth factors
      which could stimulate proliferation [chromogranin (A-CgA), PTHrp, bombesin,
      etc.], inhibit apoptosis (Survivin) and stimulate neoangiogenesis [vascular
      endothelial GF (VEGF)] of the neighbouring exocrine prostate cancer cells. NE
      differentiation appears to be a dynamic phenomenon. The NE phenotype expression
      increases during androgen-deprivation therapy and results more elevated in
      hormone refractory than in hormone sensitive disease. Pre-clinical and clinical
      studies demonstrated a direct stimulation of NE differentiation by androgen
      suppression therapy, resulting in a dramatic increase in the number of cells
      expressing NE markers. CgA appears to be the most sensitive marker and is most
      frequently used for detecting NE phenotype either at the tissue level or in the
      general circulation. Elevated plasma CgA levels are frequently observed in
      hormone-refractory disease and correlate with poor prognosis. Even in hormone
      refractory disease, NE differentiation is a time-dependent phenomenon and is not
      influenced by conventional antineoplastic treatments.

PMID- 16625865
TI  - Molecular radiotherapy with somatostatin analogs for (neuro-)endocrine tumors.
AB  - Peptide receptor radionuclide therapy (PRRT) holds great promise for the future
      regarding the treatment of various cancers. With the use of radiolabelled
      peptides, which bind with high affinity to their receptors on cancer cells, it is
      possible to target the cancer efficiently. In gastroenteropancreatic tumors,
      radiolabelled somatostatin analog therapy has proven to be effective. Dose
      limiting organs are the bone marrow and the kidneys. With the currently used dose
      schemes and kidney protection, PRRT is relatively safe and serious side-effecs
      are rare. Which radiolabelled somatostatin analog can be regarded as the most
      effective therapy cannot be concluded from the available literature. Also, the
      development of therapy strategies with combinations of different radionuclides
      and or peptides is of interest as these strategies may provide an increase in
      therapeutic efficacy in the future.

PMID- 16625866
TI  - [Comparative study between the level of discomfort and the acoustic reflex in
      workers].
AB  - BACKGROUND: Comparative study between the level of discomfort and the acoustic
      reflex in workers. AIM: To observe the hearing behavior, through the assessment
      of the contraction activity of the stapedius muscle and the level of discomfort,
      of individuals who are and are not exposed to occupational noise, with the aim of
      identifying the influence of noise in the behavior of the contraction of the
      stapedius muscle and in the sensibility of hearing. METHOD: This study was
      developed at the Servico Social da Industria - SESI - Ce. A hundred and three
      adults with normal hearing, male and female, with ages varying from 18 to 45
      years were divided in three groups: G1 with 41 adults exposed to noise and who
      used AIPE; G2 with 32 adults exposed to noise and who did not use AIPE; G3 with
      30 adults who were not exposed to noise. Participants were submitted to
      audiologic evaluation, including the analysis of the acoustic reflex level (ARL)
      and discomfort level (DL) at the frequencies of 500 HZ, 1000Hz, 2000Hz, 3000Hz,
      4000Hz and WN. For the statistical analysis the tests of Mann Whitney, Wilcoxon
      and Kruskal, with significance levels of 5%, were used. RESULTS: No statistically
      significant difference was identified for the ARL between the three groups, with
      mean values ranging from 93 to 103dBHL; the ARL was significantly smaller than
      the DL, with the mean values of DL varying from 111 to 119 dBHL for G1, from 113
      to 120dBHL for G2 and from 106 to 114dBHL for G3; the DL is higher in individuals
      of G1 followed by individuals of G2 and G3. CONCLUSION: The exposure to noise
      does not determine changes in the behavior of the ARL; the DL rises with the
      exposure to occupational noise; the DL is higher than the ARL in 10 to 25dB.

PMID- 16625867
TI  - [Boston Naming Test: performance of Brazilian population from Sao Paulo].
AB  - BACKGROUND: The Boston Naming Test is frequently used to evaluate naming
      deficits. The scores used in Brazil have been the same as those used in the
      American version. In the case of individuals with poor schooling associated to
      cerebral lesions, a frequent situation in our country, one runs the risk of
      considering a poor performance as a deficit, what in fact is a consequence of
      lack of knowledge and cultural deprivation. AIM: to evaluate the influence of age
      and schooling in the naming ability of normal individuals, from Sao Paulo city,
      in a visual confrontation task. METHOD: 133 normal volunteers, aged between 28
      and 70 years. RESULTS: the scores obtained in spontaneous naming were [mean
      (SD)]: [39.4 (9.8)]; per age group: 28 - 50 years [39.5 (10.5)], 51 - 70 years
      [39.1 (9.1)]; per schooling: 1 - 4 years [33.7 (9.6)], 5 - 8 years [36.6 (7.9)],
      9 or more [47.4 (6)]. The comparison between the performances of the two age
      groups did not reveal any significant differences. Higher educational level
      determined a better performance both in spontaneous and facilitated naming. Cues
      of stimuli were necessary for the individuals to access the correct name,
      especially for the group with lower educational level. Phonemic cues, on the
      other hand, benefited individuals with more than eight years of formal education.
      The suggested cut-off score for the test to be use in Brazil was calculated by
      the ROC curve analysis and based on the comparison between normal and aphasic
      individuals. CONCLUSION: schooling was the variable that had the greatest
      influence on performance. Although the level of difficulty of a few items may, to
      some extent, differ between English and Portuguese, the translated version of the
      BNT can be used without any adaptations for the Brazilian population, provided
      that the level of education is taken in consideration when interpreting the
      results.

PMID- 16625868
TI  - [Hearing aids: objective and subjective evaluations of linear and nonlinear
      amplification users].
AB  - BACKGROUND: Sensorineural hearing impaired individuals benefit themselves with
      the use of nonlinear amplification, once the compression tries to reestablish the
      sensation of normal loudness. However, the literature is still controversial in
      relation to the benefits for speech recognition in users of linear and nonlinear
      hearing aids. AIM: For this reason, the purpose of this study was to compare the
      performance of linear and nonlinear hearing aid users through objective and
      subjective evaluations, verifying the best circuit for hearing adaptation and
      speech recognition in silence and in noise. METHOD: 21 bilateral hearing aid
      users, who had been using the hearing aid for at least 3 months, with 12 to 64
      years of age and with mild to moderate-severe hearing losses were studied
      according to the type of amplification used, forming two groups: linear group
      composed by 10 linear hearing aid users; and nonlinear group, composed by 11
      nonlinear hearing aid users. Speech recognition tests were applied in silence and
      in noise, as well as the International Outcome Inventory of Hearing Aids
      questionnaire. RESULTS: Statistically significant differences were not observed
      between the groups for the speech recognition tests, in silence and in noise, and
      for the questionnaire. CONCLUSION: It can be concluded that no difference exists
      in the performance of linear and nonlinear hearing aids users, regarding the
      objective evaluations (speech tests) and the subjective evaluations
      (questionnaire), that indicate a better adaptation or a better speech recognition
      in silence or in noise.

PMID- 16625869
TI  - [Loudness discomfort level in normal hearing individuals].
AB  - BACKGROUND: Loudness Discomfort Level (LDL), a test used in the hearing aid
      fitting process, has also been recommended to evaluate patients with tinnitus
      and/or suspect of hyperacusis. AIM: To determine LDL reference values for normal
      hearing individuals and to correlate the LDL to the Acoustic Reflex Threshold
      (ART). METHOD: LDL was investigated in 64 normal hearing subjects, with ages
      between 18 and 25 years (53.1% female), in the frequency threshold of 0.5 to 8KHz
      and for speech (non-recorded, non-standardized connected discourse). Pulsate pure
      tones were presented for two seconds, with a one-second interval between each
      presentation. The initial stimulus intensity was at 50dB and was followed by
      ascending presentations, of 5dB each, until the subject referred initial
      discomfort with loudness. The testing procedure was performed separately in each
      ear, and was immediately repeated at the end of the test (test and retest
      situation). The choice of the ear that would start the testing procedure was
      alternated for each subject. After that contralateral acoustic reflexes ART were
      measured. The presence of the ART was indicated by a minimal needle deflection
      (larger than 0.05ml) on the emittance equipment. RESULTS: Median varied from 86
      to 98dBHL, with no statistically significant differences between gender (p >
      0.11), between ears (p > 0.36) and between the test-retest situation (p > 0.34).
      The determination coefficients (r2) of the linear regression model revealed
      absence of correlation between log(LDL) and log(ART). CONCLUSION: Normal hearing
      individuals have LDL between 86 and 98dBHL for all of the tested stimuli. Inter
      subject differences and the good reproductivity suggest that the interpretation
      of the test should be cautious and analyzed considering the patient's history.
      The test can be an useful instrument go follow-up patients. No correlation was
      found between LDL and ART.

PMID- 16625870
TI  - [Occurrence of child abuse: knowledge and possibility of action of speech
      language pathologists].
AB  - BACKGROUND: This work presents the results of an epidemiological survey about the
      professional experience of Speech-Language Pathologists and Audiologists of Rio
      de Janeiro (Brazil) with children and adolescents who are victims of domestic
      violence. AIM: To understand the occurrence of child abuse and neglect of
      children and adolescents treated by speech-language pathologists, characterizing
      the victims according to: most affected age group, gender, form of violence,
      aggressor, most frequent speech-language complaint, how the abuse was identified
      and follow-up. METHOD: 500 self-administered mail surveys were sent to a random
      sample of professional living in Rio de Janeiro. The survey forms were identified
      only by numbers to assure anonymity. RESULTS: 224 completed surveys were mailed
      back. 54 respondents indicated exposure to at least one incident of abuse. The
      majority of victims were children, the main abuser was the mother, and physical
      violence was the most frequent form of abuse. The main speech disorder was late
      language development. In most cases, the victim himself told the therapist about
      the abuse--through verbal expression or other means of expression such as
      drawings, story telling, dramatizing or playing. As the majority of the victims
      abandoned speech-language therapy, it was not possible to follow-up the cases.
      CONCLUSION: Due to the importance if this issue and the limited Brazilian
      literature about Speech-Language and Hearing Sciences and child abuse, it is
      paramount to invest in the training of speech-language pathologists. It is the
      duty of speech-language pathologists to expose this complex problem and to give
      voice to children who are victims of violence, understanding that behind a speech
      language complaint there might be a cry for help.

PMID- 16625871
TI  - [Changes in transient evoked otoacoustic emissions contralateral suppression in
      infants].
AB  - BACKGROUND: It has been suggested that the function of the medial olivocochlear
      system (MOCS) can be evaluated by the suppression effect of the transient evoked
      otoacoustic emission (TEOAE). The competitive noise has an inhibitory effect on
      the functioning of the outer hair-cell, reducing the level of otoacoustic
      emissions. Despite the fact that there is no postnatal growth of the cochlea,
      middle ear growth and auditory processing development continue after birth. AIM:
      To analyze age-related changes of MOCS using the TEOAE suppression in healthy
      infants. METHOD: 25 full-term infants with no risk factors for hearing loss were
      evaluated in two moments: at birth and at the age of six months. At both ages
      TEOAE were recorded in the "Quickscreen" mode, nonlinear stimulation at 78dB
      peSPL, for both ears, with and without contralateral noise presented at 60dB SPL.
      RESULTS: The data analyses, using ANOVA, revealed significant contralateral
      suppression of otoacoustic emissions in both groups, but the TEOAE levels and the
      amount of TEOAE contralateral suppression were smaller at six-month of age when
      compared to the neonatal period (p < 0.01). The TEOAE suppression effect for
      neonatals was 2.81dB (+/- 0.19dB) and at the age of six months was 1.41dB (+/-
      0.29dB). CONCLUSION: The amount of TEOAE suppression decreased from birth to six
      months of age. The association between contralateral acoustic stimulation and a
      commercially available rapid TEOAE measurement system enables a non-invasive
      monitoring of the auditory efferent mechanism and seems to be clinically feasible
      to evaluate cochlear status and auditory efferent function development in infants
      at risk.

PMID- 16625872
TI  - [Sonar System- digital sounds of instruments for behavior hearing tests with
      infants].
AB  - BACKGROUND: The use of musical instruments, in the clinical practice, for the
      behavioral assessment of hearing has a limited possibility to control loudness,
      and does not restrict the test situation to a determined frequency. A new method
      of testing infants is through the Sonar System. This program can be used for the
      behavioral hearing assessment of infants, with the possibility of choosing the
      frequency range and loudness in which the test will be carried out. The Sonar
      System is different from other behavioral assessment methods once it offers
      instruments with standardized sounds and is limited to certain frequency ranges;
      all controlled by the examiner. With this method, one can offer more precise
      assessments and researches with better methodological control, once the presented
      sound will not suffer interferences of the examiner. AIM: To use the Sonar System
      -digital band--to follow up the development of hearing in infants, born at term,
      from one to six months of age. METHOD: An average of 30 infants was monthly
      evaluated. For the assessment the following recordings of instruments were
      presented: clapper, ganza, coco and drum. These recordings were respectively set
      at the frequencies of 3000, 1500, 700 and 500 Hz. All infants went through evoked
      otoacoustic emissions screening. RESULTS: Statistical analysis revealed
      significant responses in all of the tested frequencies. Results indicated
      statistically significant differences in all of the tested frequencies for the
      second trimester, but not for the first one. CONCLUSION: The use of the Sonar
      System (digital band) is recommended for the behavioral hearing assessment of
      this age group. Since this is a new technique to assess behavioral hearing, the
      use of the Sonar System should be expanded to other populations and in other
      social contexts in order to allow and facilitate the assessment, diagnosis and
      intervention of infants and small children.

PMID- 16625873
TI  - [Alphabetization and rehabilitation of reading/writing disorders through a
      phonetic-visual-articulatory method].
AB  - BACKGROUND: Alphabetization and rehabilitation of reading/writing disorders
      through a phonetic-visual-articulatory method (Metodo das Boquinhas - Jardini,
      1997). This methodology combines neuropsychological inputs, such as
      sounds/phonemes, letters/graphemes to the visual representation of mouth
      position/articulemes. AIM: To alphabetize and/or rehabilitate children who
      presented reading/writing disorders, of varied etiologies, with consistent short
      term results, in a combined intervention with a speech-language pathologists and
      a psycho-pedagogue. METHOD: Participants of this study were 30 children, with the
      diagnoses of dyslexia, ADHA, mild cognitive retardation, infant psychoses and
      borderline behavior, some of which presented comorbidities. Children ranged
      between 7 and 10 years of age, all presenting at least a six-month delay in
      regular schooling. The children along with their parents and teachers took part
      in the research. Parents and teachers assessed the children through a multiple
      choice questionnaire at the beginning of treatment (T0), three (T1) and six
      months after intervention (T2), according to parameters of reading, reading
      comprehension, spelling, blackboard copying, attention, concentration and
      confidence for learning. The questionnaire qualified children as incapable,
      intermediate and capable for learning in each of the assessed parameter. The
      adopted therapeutic approach was the application of a phonetic-visual
      articulatory method, with two weekly sessions with a speech-language pathologist
      and a psycho-pedagogue. Besides the therapeutic interventions, children continued
      to attend regular school. RESULTS: An expressive development was observed for all
      of the assessed parameters, according to parents and teachers. After the first 3
      months of intervention, the performance of the children was classified at an
      intermediate level of learning and after 6 months they were considered as being
      capable for learning in each of the assessed parameters. These results not only
      favored a better performance at school, but also raised the children's self
      esteem in terms of learning. CONCLUSION: After 6 months of intervention with the
      phonetic-visual-articulatory methodology children were able to continue with
      their learning process in a regular school, following the performance of the
      other members of class.

PMID- 16625874
TI  - [Hospitalization and premature surgeries; language and psychism: a report of 2
      cases].
AB  - BACKGROUND: mutual influences between body, psychism and language. AIM: The
      purpose of this work was to analyze the possible connections between hospital
      internations and surgeries, to which children were submitted at their earliest
      life years, as well as subsequent language and psychic adversities. METHOD: It is
      a qualitative/clinical research, of a descriptive/interpretative nature, carried
      out through the longitudinal analysis of two clinical case studies with small
      children of approximately three years of age, whose families had co-occurrent
      complaints: surgeries and premature hospital internations (as a consequence of
      organical diseases) and subsequent language disorders. Clinical material was
      analyzed under a theorical perspective, articulating psychoanalytical and speech
      therapy theories, based on clinical practice. RESULTS: In both cases, speech
      therapy symptoms decreased progressively as the organic disorders gained space
      during therapeutic dialogues (between speech therapist and patient), as well as
      in home-circle narratives. This promoted modifications/surpasses of the language
      symptoms presented by the patients. CONCLUSION: The organic birth of the studied
      children was not concomitant to their symbolic birth, thus creating a gap between
      them. This gap is derived from the lack of compatibility between the development
      of corporal scheme and subjective processes. The symbolic effects suffered by
      parents due to the birth of children who are radically divergent from what was
      expected was devastating, making it impossible for parents to conceive their
      babies symbolically. After the violent impact of disappointment, these children
      remained being interpreted by their parents. This created a disturbance in the
      functioning of language and in the psychism of these children. Thus,
      unconsciously, parents were only able to represent their children based on the
      place that was originally given to them: the place of disease.

PMID- 16625875
TI  - [Relation between social cognitive aspects and the functional communicative
      profile in a group of adolescents of the autistic spectrum].
AB  - BACKGROUND: Issues concerning language development and their relation with social
      cognitive aspects give direction to the clinical practice when assisting the
      population with the diagnosis within the autistic spectrum. The deficits or
      differences in this development can result in different ways of analyzing and
      counseling this population. Adolescence becomes a question mark in this analysis
      since, in most cases, researches address only early childhood. The speech
      pathologist must assess the relationship between language abilities and
      communicative competence. Language abilities refer to the possibilities to
      understand and formulate spoken or written symbolic systems, whereas the
      communicative competence refers to the ability to use language as an effective
      tool to interact with other people in several social contexts. PURPOSE: To verify
      the development of the functional communicative profile and of the social
      cognitive aspects of adolescents, who attend a specialized institution and who
      have a psychiatric diagnosis within the autistic spectrum in three different
      situations of communication during a 12 months period and to study the relation
      between these variables in the same situations, during the same period of time.
      METHOD: Subjects of this study were five adolescents with ages between 12 and 17
      years. Two recording sets, with a 12 month interval, were obtained for each
      subject. Each recording set was composed by three 30 minutes videotaped
      situations of different interactive contexts: Situation I--individual language
      therapy; Situation II--child in a group with coordinator; Situation III--child in
      a group without coordinator. RESULTS: Differences exist between the subjects in
      the three studied situations regarding the social cognitive performance and the
      functional communicative profile. CONCLUSION: There is a relationship between the
      development of the social cognitive aspects and the functional communicative
      profile in the three situations of communication for the studied period.

PMID- 16625876
TI  - [Brazilian scientific journals in speech-language and hearing science: impact
      indicator].
AB  - BACKGROUND: Global value of scientific papers published in national journals of
      the Brazilian Speech-language and Hearing Science analyzed through the Impact
      Factor (IF). PURPOSE: To analyze part of the Brazilian Speech-Language and
      Hearing Science through its scientific journals: characterization of the impact
      indicator--in this case the Impact Factor (IF). Seven national Speech-language
      and Hearing Science journals (1986/ 2001) registered in the Brazilian Institute
      of Information in Science and Technology (Ibict) and with a given International
      Standard Serial Number (ISSN) were analyzed. In order to calculate the IF of the
      scientific journals, the lists of bibliographic references of the published
      papers were consulted and the original formula of Garfield was used, adapting it
      to the seven journals. Bibliographic references cited in the research papers, in
      the case studies, in the review and update articles were considered for analyses.
      Researches which were cited in the summaries like letters to the editors;
      editorial, abstracts, commentaries and others were excluded. A total of 9,334
      bibliographic references of 549 papers were analyzed, excluding self-citations of
      authors. It was observed that the resulting IFs revealed practically null values.
      The obtained results demonstrate that the Brazilian Speech-language and Hearing
      Science needs to develop a few aspects of its editorial and scientific processes-
      the researches of the Brazilian Speech-language and Hearing Science are being
      lost, making it necessary for the editors to raise the access and visibility of
      their journals and for the speech-language and hearing scientists to cite the
      work of their antecessors and national partners. According to the obtained data,
      for the Brazilian Speech-language and Hearing Science, the publication of 11.9
      papers is necessary for only one of these papers to be cited in another research.
      It is observed that the IFs of the Brazilian Speech-language and Hearing Science,
      among these seven journals, have risen since 1999, suggesting a development of
      this Science. The follow up of this research, analyzing the years subsequent to
      2001, is necessary in order to verify the real raise of the impact of these
      articles.

PMID- 16625877
TI  - [The long-term average spectrum in research and in the clinical practice of
      speech therapists].
AB  - BACKGROUND: One of the great difficulties in evaluating a voice is the judgment
      of quality through the perceptual auditive analysis--although frequently used--,
      as it is influenced by socioeconomic and cultural aspects as well as individual
      preferences. Many are the adjectives and methods used in this assessment,
      especially because of the subjectivity involved in the process, leading to
      incompatibilities between listeners and difficulties in reaching a consensus on
      the use of this or that terminology. In such a context, the voice laboratory and
      more specifically the acoustic computerized analysis, has guided and complemented
      speech-language treatments. Among the several possibilities of spectrographic
      analysis, the (Long-Term Average Spectrum--LTAS) quantifies the quality of
      voices, pointing differences between gender, age, professional--spoken and sang-
      and dysphonic voices. The LTAS has been used a lot in researches that investigate
      voice. As it evidences the contribution of the glottic source and of resonance to
      the quality of voice, it provides objective parameters for the evaluation of this
      aspect which usually depends on our auditive perception. AIM: to demonstrate how
      LTAS can be applied in voice research and in the speech-language therapy
      practice, describing both the technical aspects required for the production and
      interpretation of results, and its limitations. CONCLUSION: The area of voice
      research has developed a lot in these last two decades especially because of the
      advent of the voice and speech laboratory. For this reason, the knowledge about
      the applicability of more tools for voice analysis, as the LTAS, as well as the
      existing need for more studies in this area, will most certainly contribute for
      the creation of new research areas not only in the field of professional voice
      but also in the field of therapy.

PMID- 16625878
TI  - Saying no to negativism and yes to a new future.

PMID- 16625879
TI  - Tools for a healing practice.

PMID- 16625880
TI  - Undoing Answers. Finding what's right for you.

PMID- 16625881
TI  - How do I get started? Financing your new practice and preparing for roadblocks.

PMID- 16625882
TI  - Close encounters with the legal aspects of private practice.

PMID- 16625883
TI  - Entrepreneurship in holistic home-care nursing.

PMID- 16625884
TI  - Serendipities leading to private practice.

PMID- 16625886
TI  - The basics of cultural competence: a conversation with Barbara Nichols. Interview
      by Paul Padilla.

PMID- 16625885
TI  - Weaving private practice with AHNA networks.

PMID- 16625887
TI  - A mission trip to Biloxi.

PMID- 16625888
TI  - Cultural competence in clinical practice.

PMID- 16625889
TI  - Diversity, cultural competence and the nursing student.

PMID- 16625890
TI  - Culturally competent care in the workplace.

PMID- 16625891
TI  - Is cultural competency required in today's nursing care?

PMID- 16625892
TI  - Cramer-Rao lower bounds on estimation of laser system pointing parameters by use
      of the return photon signal.
AB  - Cramer-Rao lower bounds (CRLBs) on the estimation of the pointing parameters of a
      laser system using the return signal are obtained. A maximum likelihood estimator
      is found to obtain an estimation performance close to the CRLB in most scenarios
      considered.

PMID- 16625893
TI  - Generating a high-extinction-ratio pulse from a phase-modulated optical signal
      with a dispersion-imbalanced nonlinear loop mirror.
AB  - We demonstrate a method for generating ultrashort pulses from a phase-modulated
      optical signal by using a dispersion-imbalanced nonlinear loop mirror instead of
      the traditional linear dispersion medium. The extinction ratio of the pulses is
      greatly improved at the same time. By controlling the bandwidth of the phase
      modulated signal and the dispersion map of the dispersion-imbalanced nonlinear
      loop mirror, we can control the pulse width from several picoseconds to hundreds
      of femtoseconds.

PMID- 16625894
TI  - Laser-optical fiber Bragg grating anemometer for measuring gas flows: application
      to measuring the electric wind.
AB  - A novel laser-optical fiber Bragg grating anemometer (FBGA) has been devised for
      measuring the speed of a moving gas in the range 0-1.5 m s(-1). As a test, the
      FBGA was applied to measuring the speed of the electric wind generated in the
      particularly harsh, high-voltage environment of a dc, negative-polarity, partial
      (corona) discharge in atmospheric air. The instrument proved more stable and
      yielded an order-of-magnitude improvement in sensitivity (deltav approximately 4
      x 10(-3) ms(-1)) compared with other optical-fiber-based anemometers. On-axis
      wind speeds ranging from zero to 1.1 m s(-1) were measured in the vicinity of the
      corona discharge.

PMID- 16625895
TI  - Analysis of nonlinear phase noise in single-channel return-to-zero differential
      phase-shift keying transmission systems.
AB  - Self-phase modulation and intrachannel cross-phase-modulation- (IXPM) induced
      nonlinear phase noise is investigated by the variational method. IXPM can cause a
      considerable increase of phase noise. We show, however, that IXPM leads to a
      partial correlation between the phase noises of adjacent pulses, which tends to
      reduce the influence of nonlinear phase noise in return-to-zero differential
      phase-shift keying transmission. In highly dispersive transmission systems,
      intrachannel four-wave mixing-induced differential phase fluctuations are
      typically larger than differential nonlinear phase noise. The analysis is
      validated by Monte Carlo simulation.

PMID- 16625896
TI  - Passive harmonic mode-locking of a soliton Yb fiber laser at repetition rates to
      1.5 GHz.
AB  - We report passive harmonic mode locking of a soliton Yb fiber laser at repetition
      rates continuously scalable up to 1.5 GHz. The laser generates transform-limited
      500 fs pulses, with pulse energies of 30-100 pJ. At the 31st harmonic (1.3 GHz),
      the cavity supermodes are suppressed by 35 dB, and the pulse-to-pulse timing
      jitter is 6 ps.

PMID- 16625897
TI  - Known-plaintext attack on optical encryption based on double random phase keys.
AB  - We demonstrate a new approach to known-plaintext attack on an optical encryption
      scheme based on double random phase keys. With this attack an opponent can access
      both random phase keys with the help of the phase retrieval technique. This
      demonstration shows that an optical encryption scheme based on double random
      encoding is vulnerable to known-plaintext attack.

PMID- 16625898
TI  - Unitary matrices for phase-coded holographic memories.
AB  - We propose a novel type of unitary matrix for phase-code multiplexed holographic
      memories, which could be quickly generated from geometric sequences. Our analysis
      shows that the phase-code matrices are unitary rather than orthogonal. The new
      matrices have complex elements. The order of unitary matrices can be any positive
      integer, so that we can accommodate the available spatial light modulators to
      obtain the maximum possible storage capacity. The cross-talk noises in phase
      encoded memories with unitary matrices and with Hadamard matrices are of the same
      order of magnitude, which are much lower than those in holographic memories with
      wavelength multiplexing or angle multiplexing.

PMID- 16625899
TI  - Consumer holographic read-only memory reader with mastering and replication
      technology.
AB  - What is believed to be a novel holographic design for read-only memory systems
      allows a compact low-cost consumer drive within a 10 mm drive height, using a
      lensless phase conjugate readout and a combination of polytopic and angle
      multiplexing. A two-step mastering method enables production of high-efficiency
      holographic masters, and fast replication is possible by using only a series of
      plane-wave illuminations. Mastering and replication techniques are verified
      experimentally with an array of 125 holograms with no measured bit errors.

PMID- 16625900
TI  - Precision measurement with visual feedback using binary phase diffractive optical
      elements.
AB  - A novel method for obtaining precision measurements by using two binary
      diffractive optical elements is presented. The system provides visual feedback of
      the measurement without the use of electronics.

PMID- 16625901
TI  - Simultaneous single-shot measurement of temperature and pressure along a one
      dimensional line by use of laser-induced thermal grating spectroscopy.
AB  - We report a new technique, based on laser-induced thermal grating spectroscopy
      (LITGS), for time- and space-resolved simultaneous measurement of temperature and
      pressure along a one-dimensional line. LITGS signals generated in NO2/N2 mixtures
      along a 5 mm line produce a time-varying image that is recorded on a streak
      camera. The temperature is derived with a precision of 0.3% from the streak
      images using a rapid Fourier method with a spatial resolution of 150 microm along
      the line. The principle of pressure measurement is demonstrated using a sequence
      of images, and a simple extension of the method to single-shot pressure
      measurement is discussed.

PMID- 16625902
TI  - Phase-shifting interferometry in the presence of nonlinear phase steps,
      harmonics, and noise.
AB  - A phase-shifting piezo device commonly employed in phase-shifting interferometry
      exhibits a nonlinear response to applied voltage. Hence, a method for estimation
      of phase distribution in the presence of nonlinear phase steps is presented. The
      proposed method compensates for the harmonics present in the intensity fringe,
      allows the use of arbitrary phase-step values between 0 and tau rad, and does not
      impose constraints on the selection of particular phase-step values for
      minimizing nonlinearity and compensating for the harmonics. The comparison of the
      proposed method with other well-known benchmarking algorithms shows that our
      method is highly efficient and also works well in the presence of noise.

PMID- 16625903
TI  - Single-frequency operation of a broad-area laser diode by injection locking of a
      complex spatial mode via a double phase conjugate mirror.
AB  - We demonstrate what is believed to be the first phase-coherent locking of a high
      power broad-area diode to a single-frequency master laser. We use photorefractive
      double phase conjugation to lock the diode in a self-optimized complex spatial
      mode while the photorefractive crystal diffracts that complex mode in a near
      diffraction-limited beam.

PMID- 16625904
TI  - Highly efficient, 0.84 slope efficiency, 901 nm, quasi-two-level laser emission
      of Nd in strontium lanthanum aluminate.
AB  - The possibility of using direct pumping into the emitting level of the Nd3+ ion
      in magnesium-compensated strontium lanthanum aluminate (Sr(1-x)La(x
      y)Nd(y)Mg(x)Al(12-x)O19) to improve 900 nm 4F(3/2) --> 4I(9/2) laser emission is
      discussed. Selection of the composition parameters x and y for optimization of
      laser emission and reduction of heat generation is based on the spectroscopic and
      crystal growth characteristics. Pumping in the 865.5 nm absorption band
      4I(9/2)(Z1) --> 4F(3/2)(R1) transforms the laser process into a quasi-two-level
      scheme of very low (below 4%) quantum defects. A very high slope efficiency (over
      84%) for 901 nm continuous-wave laser emission is demonstrated with Ti:sapphire
      laser pumping in this band for a crystal with x = 0.4 and y = 0.05.

PMID- 16625905
TI  - Dynamic transition from modelike patterns to turbulentlike patterns in a broad
      area Nd:YAG laser.
AB  - We report the first experimental observation to our knowledge of a dynamic
      transition from modelike patterns to completely disordered patterns in a large
      aspect-ratio Nd:YAG laser. Recordings of near-field patterns with an integration
      time as small as 1 ns allow us to follow the evolution of the transverse
      intensity profile along the output pulse of the laser.

PMID- 16625906
TI  - High-power efficient diode-pumped Nd:YVO4/LiB3O5 457 nm blue laser with 4.6 W of
      output power.
AB  - Continuous-wave 457 blue laser emission at powers as high as 4.6 W is achieved by
      using a fiber-coupled laser diode array with a power of 30 W to pump 0.1 at. %
      low-doped bulk Nd:YVO4 crystal, with intracavity frequency doubling in a 15 mm
      long type I critical phase-matched LiB3O5 (LBO) crystal in a compact three-fold
      cavity with a length of less than 100 mm. The optical-optical conversion
      efficiency is greater than 15.3%, and the stability of the output power is better
      than 3% for an hour.

PMID- 16625907
TI  - Mode-coupling analysis of three-dimensional microdisk resonators by the finite
      difference time-domain technique.
AB  - Quality factor enhancement due to mode coupling is observed in a three
      dimensional microdisk resonator. The microdisk, which is vertically sandwiched
      between air and a substrate, with a radius of 1 microm, a thickness of 0.2
      microm, and a refractive index of 3.4, is considered in a finite-difference time
      domain (FDTD) numerical simulation. The mode quality factor of the fundamental
      mode HE71 decreases with an increase of the refractive index of the substrate,
      n(sub), from 2.0 to 3.17. However, the mode quality factor of the first-order
      mode HE72 reaches a peak value at n(sub) = 2.7 because of the mode coupling
      between the fundamental and the first-order modes. The variation of mode field
      distributions due to the mode coupling is also observed. This mechanism may be
      used to realize high-quality-factor modes in microdisks with high-refractive
      index substrates.

PMID- 16625908
TI  - Fiber-optic scanning two-photon fluorescence endoscope.
AB  - We report on the development of a miniature, flexible, fiber-optic scanning
      endoscope for two-photon fluorescence imaging. The endoscope uses a tubular
      piezoelectric actuator for achieving two-dimensional beam scanning and a double
      clad fiber for delivery of the excitation light and collection of two-photon
      fluorescence. Real-time imaging of fluorescent beads and cancer cells has been
      performed.

PMID- 16625909
TI  - Spectroscopic spectral-domain optical coherence microscopy.
AB  - The spectroscopic content within optical coherence tomography (OCT) data can
      provide a wealth of information. Spectroscopic OCT methods are frequently limited
      by time-frequency trade-offs that limit high spectral and spatial resolution
      simultaneously. We present spectroscopic spectral-domain optical coherence
      microscopy performed with a multimodality microscope. Restricting the spatial
      extent of the signal by using high-numerical-aperture optics makes high
      resolution spectroscopic information accessible, facilitated with spectral-domain
      detection. Simultaneous acquisition of multiphoton microscopy images is used to
      validate tissue structure and localization of nuclei within individual cells.

PMID- 16625910
TI  - Feasibility of diffuse optical imaging with long-lived luminescent probes.
AB  - Long-lived near-infrared phosphors with high quantum yields have recently become
      available, making it possible to image oxygen distributions in tissue in three
      dimensions. By numerical simulations we demonstrate that, by using phosphorescent
      probes with appropriate oxygen quenching constants, one can image hypoxic
      phantoms in scattering media with adequate spatial resolution, employing simple
      time-gated measurements. The approach developed will guide experimental imaging
      of phosphorescence lifetime and oxygen pressure in living tissue.

PMID- 16625911
TI  - Highly sensitive detection of biomolecules with the magneto-optic surface-plasmon
      resonance sensor.
AB  - The characteristics of a novel magneto-optic surface-plasmon-resonance (MOSPR)
      sensor and its use for the detection of biomolecules are presented. This physical
      transduction principle is based on the combination of the magneto-optic activity
      of magnetic materials and a surface-plasmon resonance of metallic layers. Such a
      combination can produce a sharp enhancement of the magneto-optic effects that
      strongly depends on the optical properties of the surrounding medium, allowing
      its use for biosensing applications. Experimental characterizations of the MOSPR
      sensor have shown an increase in the limit of detection by a factor of 3 in
      changes of refractive index and in the adsorption of biomolecules compared with
      standard sensors. Optimization of the metallic layers and the experimental setup
      could result in an improvement of the limit of detection by as much as 1 order of
      magnitude.

PMID- 16625912
TI  - Estimating optical properties in layered tissues by use of the Born approximation
      of the radiative transport equation.
AB  - We use the Born approximation of the radiative transport equation to recover
      simultaneously the absorption and scattering coefficients in a single layer of a
      two-layer tissue sample from reflectance data. This method reduces the estimation
      of both optical properties to a single linear, least-squares problem. It is valid
      over length scales smaller than a transport mean free path and hence is useful
      for epithelial tissue layers. We demonstrate the accuracy of this method by using
      spatially resolved reflectance data computed with Monte Carlo simulations.

PMID- 16625913
TI  - Simultaneous compensation for spatial and temporal dispersion of acousto-optical
      deflectors for two-dimensional scanning with a single prism.
AB  - The dispersive nature of the acousto-optical deflector (AOD) presents a challenge
      to applications of two sequential orthogonal AODs (a two-dimensional AOD) as XY
      scanners in multiphoton microscopy. Introducing a prism before the two
      dimensional (2D) AOD allows both temporal and spatial dispersion to be
      compensated for simultaneously. A 90 fs laser pulse was broadened to 572 fs
      without compensation, and 143 fs with compensation. The ratio of long axis to
      short axis of the exiting laser beam spot was 3.50 without compensation and 1.14
      with compensation. The insertion loss was 37%. Two-photon fluorescence microscopy
      used the compensated 2D AOD scanner to image a fluorescent microsphere, which
      improves signal intensity -15-fold compared with the uncompensated scanner.

PMID- 16625914
TI  - Mid-infrared single-photon counting.
AB  - We report a procedure to detect mid-infrared single photons at 4.65 microm by
      means of a two-stage scheme based on sum-frequency generation, by using a
      periodically poled lithium niobate nonlinear crystal and a silicon avalanche
      photodiode. An experimental investigation shows that, in addition to a high
      timing resolution, this technique yields a detection sensitivity of 1.24 pW with
      63 mW of net pump power.

PMID- 16625915
TI  - Semidiscrete composite solitons in arrays of quadratically nonlinear waveguides.
AB  - We demonstrate that an array of discrete waveguides on a slab substrate, both
      featuring chi2 nonlinearity, supports stable solitons composed of discrete and
      continuous components. Two classes of fundamental composite soliton are
      identified: ones consisting of a discrete fundamental-frequency (FF) component in
      the waveguide array, coupled to a continuous second-harmonic (SH) component in
      the slab waveguide, and solitons with an inverted FF/SH structure. Twisted bound
      states of the fundamental solitons are found, too. In contrast with the usual
      systems, the intersite-centered fundamental solitons and bound states with the
      twisted continuous components are stable over almost the entire domain of their
      existence.

PMID- 16625916
TI  - Stable rotating dipole solitons in nonlocal optical media.
AB  - We reveal that nonlocality can provide a simple physical mechanism for
      stabilization of multihump optical solitons and present what we believe to be the
      first example of stable rotating dipole solitons and soliton spiraling, which are
      known to be unstable in all types of realistic nonlinear media with a local
      response.

PMID- 16625917
TI  - Parametric amplification of few-cycle carrier-envelope phase-stable pulses at 2.1
      microm.
AB  - We demonstrate an optical parametric chirped-pulse amplifier producing infrared
      20 fs (3-optical-cycle) pulses with a stable carrier-envelope phase. The
      amplifier is seeded with self-phase-stabilized pulses obtained by optical
      rectification of the output of an ultrabroadband Ti:sapphire oscillator. Energies
      of -80 microJ with a well-suppressed background of parametric superfluorescence
      and up to 400 microJ with a superfluorescence background are obtained from a two
      stage parametric amplifier based on periodically poled LiNbO3 and LiTaO3
      crystals. The parametric amplifier is pumped by an optically synchronized 1 kHz,
      30 ps, 1053 nm Nd:YLF amplifier seeded by the same Ti:sapphire oscillator.

PMID- 16625918
TI  - Three-dimensional recognition of occluded objects by using computational integral
      imaging.
AB  - We have proposed a method to recognize partially occluded three-dimensional (3D)
      objects by using 3D volumetric reconstruction integral imaging (II). An II system
      captures multiple perspectives of occluded objects by using a microlens array.
      The reconstruction of the occluded 3D scene and target recognition are done
      digitally to reduce the effects of the occlusion. To verify system performance,
      we have implemented an optimum filter for object recognition. Both two
      dimensional (2D) images and 3D II volumetric reconstructed images are considered.
      The correlation results of occluded 3D images for volumetric reconstruction show
      substantial improvements compared with those for conventional 2D imaging of
      occluded images.

PMID- 16625919
TI  - Tunable superprism and polarization splitting in a liquid crystal infiltrated two
      dimensional photonic crystal made of silicon oxynitride.
AB  - Tunable superprism and polarization splitting effects, based on liquid-crystal
      infiltrated two-dimensional photonic crystal with SiON as a background material,
      are demonstrated. Owing to the strong birefringence of the liquid crystal, the
      dispersion curves of the two polarizations are distinctly different, resulting in
      large splitting between the two polarizations. Extremely large splitting, as
      large as 80 degrees, can be obtained. Moreover, the splitting can be tuned to a
      substantial degree when the optic axis of the liquid crystal is reoriented. Fully
      controllable, incident-angle-dependent and wavelength-dependent superprism
      effects are also demonstrated. This large swing in the refraction can be
      completely switched off by reorientation of the optic axis of the liquid crystal,
      thus to resemble bulk media refraction.

PMID- 16625920
TI  - Voltage-controlled liquid-crystal terahertz phase shifter and quarter-wave plate.
AB  - Phase shift exceeding tau/2 at 1 THz is demonstrated by using electrically
      controlled birefringence in a homeotropically aligned nematic liquid crystal (E7)
      cell, 570 microm in thickness. The driving voltage required for a phase shift of
      90 degrees is 125 V (rms). We demonstrate that the phase shifter works as an
      electrically switchable quarter-wave plate at 1 THz. The device can also be used
      as an electrically tuned phase compensator around the quarter-wave point near 1
      THz.

PMID- 16625921
TI  - Upper bound imposed on responsivity of optical modulators.
AB  - I study theoretically the responsivity of optical modulators. For the case of a
      linear response, by using perturbation theory I find an upper bound imposed on
      the responsivity. For the case of a two-mode modulator I find a lower bound
      imposed on the optical path required for achieving full modulation when the
      maximum birefringence strength is given.

PMID- 16625922
TI  - Terahertz surface-wave resonant sensor with a metal hole array.
AB  - A surface-wave sensor based on the resonant transmission characteristics of metal
      hole arrays is demonstrated in the terahertz (THz) region. Since the frequency of
      the transmission peak of a metal hole array, which corresponds to the resonant
      frequency of the surface waves, is particularly sensitive to the refractive index
      in the vicinity of the metal surface, a very small change in the substances
      attached to the surface can be detected by monitoring the transmission spectrum.
      By attaching a layer of substance (thickness t < 5 microm) much thinner than the
      wavelength of the THz wave (lambda(THz) = 1 mm at 0.3 THz) to the surface of a
      metal hole array, we demonstrated that the existence of such a small amount of
      substance can be detected more easily than without the metal hole array. This
      demonstration of THz sensing with metal hole arrays indicates the possibility of
      realizing THz surface-wave sensors for biochemical molecules in the THz region.

PMID- 16625923
TI  - Backscattered polarization patterns, optical vortices, and the angular momentum
      of light.
AB  - We demonstrate that the polarization patterns observed in backscattering of
      linearly polarized light are a manifestation of the conservation of angular
      momentum of light. We will show that this phenomenon can be described in terms of
      phase vortices that are acquired by the right and left circularly polarized
      components. The helicity and orbital angular momentum of these components satisfy
      the requirement for conservation of angular momentum.

PMID- 16625924
TI  - Negative and positive lateral shift of a light beam reflected from a grounded
      slab.
AB  - We consider the lateral shift (LS) of a light beam reflecting from a dielectric
      slab backed by a metal. It is found that the LS of the reflected beam can be
      negative while the intensity of reflected beam is almost equal to the incident
      one under a certain condition. The explanation for the negativity of the LS is
      given in terms of the interference of the reflected waves from the two
      interfaces. It is also shown that the LS can be enhanced or suppressed under some
      other conditions. The numerical calculation on the LS for a realistic Gaussian
      shaped beam confirms our theoretical prediction.

PMID- 16625925
TI  - Reflectionless tunneling of light in gradient optics.
AB  - We analyze the optical (or microwave) tunneling properties of electromagnetic
      waves passing through thin films presenting a specific index profile that
      provides a cutoff frequency when the films are used below this frequency. We show
      that, contrary to the usual case of a square index profile, where tunneling is
      accompanied by a strong attenuation of the wave due to reflection, such films
      present the possibility of reflectionless tunneling, where the incoming intensity
      is totally transmitted.

PMID- 16625926
TI  - Joint spectrum of photon pairs measured by coincidence Fourier spectroscopy.
AB  - We propose and demonstrate a method for measuring the joint spectrum of photon
      pairs via Fourier spectroscopy. The biphoton spectral intensity is computed from
      a two-dimensional interferogram of coincidence counts. The method has been
      implemented for a type-I downconversion source using a pair of common-path Mach
      Zehnder interferometers based on Soleil compensators. The experimental results
      agree well with calculated frequency correlations that take into account the
      effects of coupling into single-mode fibers. The Fourier method is advantageous
      over scanning spectrometry when detectors exhibit high dark count rates leading
      to dominant additive noise.

PMID- 16625927
TI  - Experimental demonstration of quantum entanglement between frequency
      nondegenerate optical twin beams.
AB  - The quantum entanglement of amplitude and phase quadratures between two intense
      optical beams with a total intensity of 22 mW and a frequency difference of 1 nm,
      which are produced from an optical parametric oscillator operating above
      threshold, is experimentally demonstrated with two sets of unbalanced Mach
      Zehnder interferometers. The measured quantum correlations of intensity and phase
      are in reasonable agreement with the results calculated based on a semiclassical
      analysis of the noise characteristics given by Fabre et al. [J. Phys. (France)
      50, 1209 (1989)].

PMID- 16625928
TI  - Enhanced surface-plasmon resonance absorption in metal-dielectric-metal layered
      microspheres.
AB  - We present a theoretical study of the dispersion relation of surface-plasmon
      resonances of mesoscopic metal-dielectric-metal microspheres. By analyzing the
      solutions to Maxwell's equations, we obtain a simple geometric condition for
      which the system exhibits a band of surface-plasmon modes whose resonant
      frequencies are weakly dependent on the multipole number. Using a modified Mie
      calculation, we find that a large number of modes belonging to this flat
      dispersion band can be excited simultaneously by a plane wave, thus enhancing the
      absorption cross section. We demonstrate that the enhanced absorption peak of the
      sphere is geometrically tunable over the entire visible range.

PMID- 16625929
TI  - Ultraviolet laser filaments for remote laser-induced breakdown spectroscopy
      (LIBS) analysis: applications in cultural heritage monitoring.
AB  - We report experiments with subpicosecond UV laser filaments for the remote
      analysis of samples related to objects of cultural heritage. The classic laser
      induced breakdown spectroscopy (LIBS) technique finds new avenues through
      femtosecond filamentation, and dynamic remote LIBS becomes possible. Advantages
      such as self-regulated laser intensity deposition on the target suggest that
      there is significant potential for using UV femtosecond filaments for the remote
      analysis of sculpture and large monuments.

PMID- 16625930
TI  - Measurement of surface concentration of fluorophores by fluorescence fluctuation
      spectroscopy.
AB  - Fluorescence fluctuation spectroscopy is applied to study molecules passing
      through a small observation volume, usually subjected to diffusive or convective
      motion in a liquid phase. We suggest that such a technique could be used to
      measure the areal absolute concentration of fluorophores deposited on a substrate
      or embedded in a thin film, with a resolution of a few micrometers. The principle
      is to translate the solid substrate in front of a confocal fluorescence
      microscope objective and to record the subsequent fluctuations of the
      fluorescence intensity. The validity of this concept is investigated on model
      substrates (fluorescent microspheres) and DNA biochips.

PMID- 16625931
TI  - High-repetition-rate 12 fs pulse amplification by a Ti:sapphire regenerative
      amplifier system.
AB  - We demonstrate the direct generation of 12 fs pulses from a Ti:sapphire
      regenerative amplifier system at a 1 kHz repetition rate utilizing properly
      designed broadband components for chirped-pulse amplification. Optimized designs
      of a regenerative amplifier with a multilayer gain-narrowing compensator and an
      adaptive dispersion compensator with a spatial light modulator contribute to the
      shorter pulse amplification.

PMID- 16625932
TI  - Multimilliwatt ultrashort pulses continuously tunable in the visible from a
      compact fiber source.
AB  - We report on a single-pass device that efficiently converts the broadband near
      infrared output from a femtosecond fiber laser into a narrow spectrum in the
      visible. With fan-out poled MgO:LiNbO3 we obtain sub-picosecond, continuously
      tunable pulses in the 520-700 nm range. Conversion efficiencies as high as 30%
      are observed at typical pump power levels of 30 mW, corresponding to average
      output powers up to 9.5 mW. The specifications of our device are ideal for
      applications in confocal microscopy and frequency metrology.

PMID- 16625933
TI  - Heterodyne spectral interferometry for multidimensional nonlinear spectroscopy of
      individual quantum systems.
AB  - A novel implementation of transient nonlinear spectroscopy is presented that
      allows the study of the transient nonlinear polarization emitted from individual
      electronic transitions. Both the amplitude and the phase of the polarization are
      retrieved, permitting the implementation of multidimensional spectroscopy in the
      excitation pulse delays. The technique is shown to detect mutual coherent
      coupling in a group of individual, localized excitonic transitions.

PMID- 16625934
TI  - In situ broadband pulse compression for multiphoton microscopy using a shaper
      assisted collinear SPIDER.
AB  - The characterization and control of the phase of broadband femtosecond pulses in
      nonlinear microscopy are successfully demonstrated with a collinear configuration
      of spectral shear interferometry for direct electric field reconstruction
      (SPIDER). A femtosecond-pulse shaper is used as a dispersionless interferometer
      for the measurement of the spectral phase and to actively compress a broadband
      supercontinuum from a photonic crystal fiber. This allows in situ online phase
      management and enables the application of quantum control spectroscopy in
      microenvironments.

PMID- 16625935
TI  - High-repetition-rate white-light pump-probe spectroscopy with a tapered fiber.
AB  - We have realized a 76 MHz white-light differential transmission spectroscopy
      system. The technique employs a Ti:sapphire laser oscillator and a tapered fiber
      to generate a white-light continuum spanning almost the full visible to near
      infrared spectral range. Using acousto-optical modulation and subsequent lock-in
      detection, transient relative transmission changes as small as 10(-5) are
      detected. The method is applied to study the ultrafast gain dynamics of the
      active layer of a vertical-external-cavity surface-emitting laser based on a
      multiple-quantum-well structure.

PMID- 16625936
TI  - Neighborhood deterioration, social skills, and social relationships in late life.
AB  - This study is designed to test two hypotheses. The first specifies that older
      adults who live in dilapidated neighborhoods will receive less social support and
      encounter more negative interaction with family and friends. The second
      hypothesis proposes that the relationship between deteriorated neighborhood
      conditions and social relationships will depend upon whether older study
      participants have strong social skills. Data from a recent nationwide survey of
      older adults suggest that living in run-down neighborhoods is associated with
      more negative interaction; however, residing in disadvantaged neighborhoods is
      not related to the amount of support older people receive from significant
      others. But perhaps more important, the findings further reveal that the effects
      of living in run-down neighborhoods on social support and negative interaction
      are completely offset for older individuals who possess strong social skills.

PMID- 16625937
TI  - Cognitive abilities of Alzheimer's patients: perceptions of Black and White
      caregivers.
AB  - This study compared Black (n = 97) and White (n = 143) family caregivers
      regarding the relationship between subjective and objective cognitive assessments
      of Alzheimer's patients from the Memphis site of the NIA/NINR Resources for
      Enhancing Alzheimer's Caregivers Health (REACH) randomized clinical trial. Black
      and White caregivers' subjective ratings (Pearlin Cognitive Status Scale) of
      their care recipients' cognitive abilities were equivalent, but White Alzheimer's
      patients had higher objective cognitive performance (Mini-Mental State
      Examination). In simple regression analysis, race was significantly related to
      differences between subjective and objective cognitive assessments and remained
      so when caregiver age, sex, income, education, relationship to care recipient,
      caregiver bother (burden), and care recipient sex were statistically controlled
      in multiple regression analysis. Compared to the other group, Black caregivers
      generally overrated, and White caregivers underrated, their care recipient's
      cognitive ability. This difference in caregiver's appraisal may affect clinical
      and behavioral interventions for dementia patients and their caregivers.

PMID- 16625938
TI  - Physiological reactivity to cognitive stressors: variations by age and
      socioeconomic status.
AB  - The present study focused on age and SES differences in stress reactivity in
      response to cognitively challenging tasks. Specifically, we assessed within
      person trajectories of cortisol, a steroid hormone released by the adrenal gland
      in response to stressors, before, during, and after exposure to cognitively
      challenging tasks. We extend the current literature by simultaneously examining
      age and SES differences in physiological reactivity. Findings suggest that age
      and SES both play an important role in reactivity, such that it was the older
      adults with higher SES who were the most physiologically reactive to cognitive
      stressors. Implications of these findings for cognitive aging research are
      discussed.

PMID- 16625939
TI  - Bringing the law to the gerontological stage: a different look at movies and old
      age.
AB  - Films often portray the complexities of real-life aging issues, showing how they
      are apparently handled outside of and around the law or legal issues.
      Furthermore, films considering the aged and the social issues associated with
      aging also reveal how the law actually functions as a framework around and within
      which people develop customs, habits, and behaviors related to the issue of old
      age. Exposing these hidden socio-legal boundaries allows us to better understand
      both the films concerned and the place of law within our aging society. In an
      attempt to better understand these issues, this article deconstructs five
      relatively modern and well-known films. All feature aged protagonists, and all
      tell their stories against a background of legal issues that are only alluded to,
      and remain hidden "behind the scenes." Two main questions are addressed by this
      analysis: First, to what extent does the reality of old age as described in the
      films considered here reflect familiar social phenomena identified by empirical
      studies? And, second, to what extent does the legal infrastructure embedded in
      the narrative of these films reflect the legal regulations that govern the aged
      in today's society. The conclusions that arose from the analysis of the cinematic
      and the legal reality expressed in the films demonstrate that the current level
      of discourse on major issues in social gerontology ignores the importance and
      relevance of law. Therefore, it behooves us to "bring the Law to the
      gerontological stage," where the current situation as it actually exists can be
      analyzed and perhaps even changed.

PMID- 16625940
TI  - Understanding associations of control beliefs, social relations, and well-being
      in older adults with osteoarthritis.
AB  - Control beliefs and social relationships have been individually assessed in
      relation to adaptation to chronic illness, although only rarely together.
      Further, some control scales show psychometric limitations in older adult
      samples. To address these concerns, a scale assessing external control was
      created by factor analyzing the items from Levenson's (1974) control subscales.
      We tested the association of external control beliefs, measured with the new
      formulation of items, and two social relations variables (support and strain) to
      well-being measures in a sample of older adults reporting osteoarthritis (OA; N =
      95, 72% female). We also compared the new formulation of items to the original
      subscales. The Levenson measures were significantly related to life satisfaction
      after controlling for social relations. However, the new externality scale was a
      stronger correlate than the chance subscale (though not different from powerful
      others). Only the new scale was related to depressive symptoms once social
      relations were controlled. In addition, social support was significantly
      associated with both outcomes.

PMID- 16625941
TI  - Possibilities for fertility restoration: a new surgical technique.
AB  - Previously published work concluded that uterine artery microvascular anastomosis
      in the porcine model was feasible with subsequent normal vascular function in
      pregnancy. of the anastomosed vessels. The objective of this study was to assess
      the feasibility of uterine autotransplantation in a porcine model using
      microvascular anastomoses. Eight large white/landrace sows of proven fertility
      were used. A supracervical hysterectomy with or without bilateral salpingo
      oophorectomy (BSO) was performed. After 1 hour of cold storage in a transplant
      solution, the specimen was reintroduced and followed by stepwise vascular
      reanastomosis. Objective perfusion index measurements suggested adequate uterine
      perfusion after transplantation. Postoperatively, sow 1 survived to 3 months with
      no signs of oestrus, and sows 2, 6, and 8 were killed on days 6, 33, and 54,
      respectively, for pelvic infection. Histopathology of the uterine grafts revealed
      gradual vessel thromboses. Microvascular reanastomosis is feasible, however,
      unsuccessful in uterine autotransplantation because of gradual vessel thromboses.
      The porcine model is highly susceptible to postoperative infection.

PMID- 16625942
TI  - Is it feasible to use a large vessel patch with a uterine allograft en bloc for
      uterine transplantation?
AB  - Uterine auto-transplantation in the porcine model using a microvascular
      anastomotic technique failed because of gradual vessel thromboses. A
      macrovascular patch harvest with the uterus en bloc is probably less likely to
      undergo vessel thrombosis. The objective of this study was to assess the
      feasibility of an aortic/inferior vena caval vascular patch harvest with the
      uterus en bloc for uterine cross-transplantation purposes. A preserved human
      cadaver and freshly killed porcine and rabbit cadaveric models were used. The
      infrarenal aorta, inferior vena cava, common and internal iliac vessels and the
      uterine arterial and venous tree together with the uterus en bloc were
      successfully harvested intact as a large vessel patch and graft in both animal
      and human models. A macrovascular patch for uterine cross-transplantation is
      technically easy and feasible to harvest en bloc with the uterus in fresh
      cadaveric donors. This technique precludes live donors and makes cadaveric organ
      donation essential.

PMID- 16625943
TI  - Leiomyosarcoma of the inferior vena cava: a case report and review of literature.
AB  - Tumors of the inferior vena cava are rare, and most of these are leiomyosarcomas.
      They are most frequent in the sixth decade of life, with a female predominance.
      We present a 45-year-old male patient with a tumor involving the entire extent of
      the inferior vena cava. Computerized tomography revealed a heterogeneously
      enhancing mass with marked expansion of the inferior vena cava with extraluminal
      extension. Computerized tomography--guided biopsy of the extraluminal component
      showed features of a fasciculated spindle cell tumor positive for vimentin,
      smooth muscle actin, and calponin and negative for S-100 antigen. We discuss the
      clinical presentation imaging findings and review the literature.

PMID- 16625944
TI  - Anatomic resection for severe blunt liver trauma.
AB  - Despite recent advances in management of severe blunt liver trauma, the operative
      mortality rate in patients with complicated blunt liver trauma (grades IV and V)
      is still high. The purpose of this study was to assess the results of anatomic
      liver resection for severe liver trauma in the institution in which liver
      transplant surgeons are responsible for the management of liver injuries.

PMID- 16625945
TI  - Carcinoid tumor of the thymus: a clinicopathologic report of two cases with a
      review of the literature.
AB  - Thymic carcinoid, a tumor with neuroendocrine-derived cells, is extremely rare.
      Its clinical and pathological features are distinct from other thymic tumors or
      carcinoids in other organs. The prognosis is poorer compared with other thymic
      tumors. Herein, we describe two cases with thymic carcinoids that were completely
      resected and underwent radiotherapy after surgery. The postoperative follow-up
      periods were 7 years and 7 months. These rare cases are discussed in light of the
      clinico-pathological picture of thymic carcinoid reported in the literature.

PMID- 16625946
TI  - Extra-adrenal nonfunctional retroperitoneal paraganglioma: case report and review
      of the literature.
AB  - An extra-adrenal paraganglioma is a rare tumor derived from the chromaffin cells
      of sympathetic ganglia. This report documents a rare case of nonfunctional extra
      adrenal paraganglioma in a 20-year-old woman with persistent flank pain.
      Ultrasonography and computed tomography revealed a solid mass with calcification
      in center, measuring 7 x 6 x 6 cm, and localized in the left upper para-aortal
      retroperitoneal region. Absence of typical clinical symptoms made a correct
      preoperative diagnosis unlikely. Tumor was successfully removed through a midline
      laparotomy incision, and pathological analysis of the surgical specimen revealed
      a paraganglioma. After 12 months, the patient is still in a good health,
      asymptomatic, and without evidence of tumor recurrence. This case emphasizes the
      necessity to include extra-adrenal paraganglioma in the differential diagnosis
      and management of retroperitoneal tumors, despite its rarity.

PMID- 16625947
TI  - Primary lymphoma of the spleen: an experience with seven patients.
AB  - Primary lymphoma of the spleen is a rare clinical entity. In our study, a group
      of 110 patients with various hematological disorders were subjected to
      splenectomy over a period of 20 years. We have been able to isolate 7 patients
      with primary lymphoma of the spleen. Main indications of splenectomy in these
      patients were anemia and leukopenia. There was no mortality, but morbidity was
      quite high (43%). We conclude that splenectomy may be a useful treatment in
      patients with cytopenias secondary to primary lymphoma of the spleen refractory
      to other types of therapy.

PMID- 16625948
TI  - Endoscopic thoracic sympathetic block by clipping for recurrent palmar
      hyperhidrosis.
AB  - Postoperative complications of endoscopic thoracic sympathectomy may be
      troublesome in some patients. Between January 1998 and September 2002, a total of
      16 patients with recurrent palmar hyperhidrosis underwent video-assisted
      thoracoscopic T2 and T3 sympathetic block. There were seven men and nine women,
      with a mean age of 21.1 years (range, 12-35 years). All patients were placed in a
      semi-sitting position under single-lumen intubated anesthesia. We performed the
      T2 sympathetic block for patients with still intact T2 ganglion using an 8-mm, 0
      degrees thoracoscope. An additional T3 block should be given if patients received
      either previous T2 sympathectomy or elevated palmar temperature <1 degrees C
      after T2 sympathetic block. The mean operation time was 30 minutes. The level of
      sympathetic blocks were the T2 and T3 in five patients, only T2 block in four,
      patients, and only T3 block in seven patients. Improvement of palmar
      hyperhidrosis can be obtained in all patients. One patient received a reverse
      operation 12 days after the T2 and T3 clipping and obtained improvement of
      troublesome compensatory sweating and dry hands 1 day after removal of all clips.
      All patients obtained improvement of palmar hyperhidrosis without recurrence
      after a mean of 37.1 months of follow-up (range, 12-56 months). Endoscopic
      thoracic T2 with or without T3 sympathetic block by clipping is a safe and
      effective method in treating patients with recurrent palmar hyperhidrosis.

PMID- 16625949
TI  - Sacral osteoblastoma presenting as a L5-S1 disc herniation.
AB  - Osteoblastoma is an uncommon neoplasm of the bone accounting for only 0.5-2% of
      all primary bone tumors. It constitutes 9% of all primary bone tumors arising in
      the sacrum. The symptoms have a wide spectrum of variety and the diagnosis is
      often delayed. We report a case of sacral osteoblastoma in a 20-year-old man who
      presented with classical symptoms of postero-lateral herniation of L5-S1
      vertebral disc. The clinical and radiographic findings are discussed as well as
      the surgical treatment.

PMID- 16625950
TI  - Small necrotic liver metastasis with microscopic tumor embolism in hepatic vein:
      a case report and review of the literature.
AB  - Small liver metastasis of rectal carcinoma is mostly solid and rarely accompanied
      by necrosis. Microscopic invasion of the hepatic vein is rare in colorectal
      metastasis. A 53-year-old man, 2 years after rectal carcinoma resection, was
      noted to have a 15-mm liver tumor. On imaging, it was difficult to determine if
      the mass was hepatic abscess, cyst, solitary necrotic nodule, or liver
      metastasis. The resected tumor was metastatic liver cancer, the center of which
      had mostly atheromatous necrosis. Also, a microscopic tumor embolism was detected
      in the hepatic vein around the tumor. Liver tumors that grow should be suspected
      of being malignant and be resected.

PMID- 16625951
TI  - Colonic injuries (primary repair and proximal colostomy).
AB  - This paper compares the outcome of colonic injuries (primary repair and proximal
      colostomy) in 94 cases. It concludes that certain risk factors are of predictive
      value in case of colon injuries (eg, gross fecal contamination, more than two
      visceral injuries, more than four units of blood transfusion, and extensive
      colonic injuries) irrespective of type of operation performed. Primary repair is
      debatable; however, in the present antibiotic era, it is safe and less costly
      than the two-stage procedure of proximal colostomy with repair. Primary repair
      can be performed in almost all cases except in certain selected cases that are
      decided on the table, taking into account the above risks factors. Mortality in
      cases of colonic injuries is associated with risk factors rather than colonic
      injury itself.

PMID- 16625954
TI  - Staying "connected''.

PMID- 16625952
TI  - Is wide excision sufficient as treatment for malignant fibrous histiocytomas of
      the trunk in children?
AB  - The aim of this study was to review our experience of treatment and outcome for
      malignant fibrous histiocytomas (MFH) of the trunk in children. The results
      suggested that wide excision only is sufficient treatment for trunk MFH in
      pediatric patients.

PMID- 16625955
TI  - Chronic headache.

PMID- 16625956
TI  - Cerviogenic headache.
AB  - Cervicogenic headache has historically been misdiagnosed, ultimately leading to
      misguided therapies. Even with the growing body of literature in the field of
      headache, this particular entity is still vastly understudied. Efforts should be
      made to encourage appropriate clinical studies in order to provide evidence based
      therapeutic modalities for this patient population. The dental professional is
      provided with the unique opportunity to see these patients on a regular basis
      without the time constraints now shouldered by our physician colleagues. The goal
      of any health care provider should be to provide the most comprehensive, multi
      modal and/or multidisciplinary care possible in our field of expertise. Expanding
      our practice model to include a more comprehensive approach to patient care has
      the potential to not only help an underserved population of pain patients but
      also provide the practitioner with the reward of heartfelt gratitude when pain
      relief is provided.

PMID- 16625957
TI  - Clinical evaluation of orthodontic self-etching primers.

PMID- 16625958
TI  - Behavior of superelastic NiTi archwire.

PMID- 16625959
TI  - Instrumentation for aesthetic dentistry: preparation for a two-unit fixed partial
      denture (FPD).

PMID- 16625960
TI  - Ain't worth a spit.

PMID- 16625961
TI  - Oral and maxillofacial pathology case of the month. Malignant lymphoma, diffuse
      large B cell type.

PMID- 16625962
TI  - Histopatholgical spectrum of thymic neoplasms: twelve-year experience at a
      referral hospital in north India.
AB  - This study was undertaken to determine the histopathological spectrum and
      clinical profile of thymic neoplasms at a tertiary referral care centre. A total
      of 96 thymectomy specimens were received during the study period (1992-2004),
      which consisted of 54 neoplasms and 42 benign lesions. Among the neoplasms there
      were 48 thymic epithelial tumors, 3 thymolipomas and 3 thymic carcinoids. The
      former comprised of 36 male (75%) and 12 female patients (25%) ranging in age
      from 2-70 years (mean 37 years). Among paraneoplastic syndromes in thymic
      epithelial tumours, 27 out of 48 (56.25%) cases were associated with myasthenia
      gravis and one case was associated with pure red cell aplasia. The most frequent
      histological subtype was cortical thymoma (43.24%) followed by predominantly
      cortical (24.32%) and well-differentiated thymic carcinoma (18.92%). On staging,
      all cases of mixed and predominantly cortical subtype were stage 1 whereas one
      medullary and 2 cortical thymomas and 4 well differentiated thymic carcinoma
      (WDTC) showed pleural and pericardial invasion (stage III). This study has
      revealed that half of thymic epithelial tumours presented as myasthenia gravis.
      The cortical thymoma was the most frequently encountered histologic subtype and
      most commonly associated with myasthenia gravis.

PMID- 16625963
TI  - Adrenocortical carcinomas: a 12-year clinicopathologic study of 15 cases.
AB  - Adrenal cortical carcinomas are rare neoplasms and the definitive diagnostic
      criteria are distant metastasis and / or local invasion. Due to advances in
      imaging techniques, adrenal cortical neoplasms are discovered earlier and are
      smaller, increasing the need for more accurate diagnosis and pathologic
      indicators of prognosis. A twelve year retrospective clinicopathologic analysis
      of 15 histopathologically proven cases of adrenocortical carcinomas was done.
      Clinical details including radiologic findings, endocrine manifestations and
      gross finding were analysed. Hematoxylin and eosin stained slides were reviewed.
      Emphasis was on application of Weiss criteria. All fifteen tumors fulfilled Weiss
      criteria of malignancy, ie. all 15 possessed 3 or more of these criteria of
      malignancy. Functional tumors showed a greater representation of mixed cell type.
      It was concluded that Weiss criteria is easy to apply and that a combined
      evaluation of clinical features, size, weight and microscopic appearance seems
      necessary for the diagnosis of adrenocortical carcinomas.

PMID- 16625964
TI  - Interleukin 2 receptor expression in renal biopsies and the diagnosis of acute
      allograft rejection.
AB  - The aim of the study is to test the diagnostic usefulness of assessing
      interleukin 2 receptor (IL2R) expression in infiltrating lymphocytes in renal
      biopsies from patients with suspected acute renal allograft rejection and to
      compare the NIH-CCTT and the Banff 97 systems of classifying the histopathologic
      changes in acute renal allograft rejection. The expression of interleukin 2 (IL2)
      and IL2R, as shown immuno-histochemically, is the final step in T cell mediated
      acute renal allograft rejection. Renal biopsies obtained from 40 patients
      clinically suspected to have early acute allograft rejection were examined
      histologically to diagnose acute allograft rejection and classified by the two
      systems. Frozen sections of the biopsies were stained with specific antibody for
      the presence of IL2R. 31 of the 40 patients were histologically and clinically
      confirmed to have acute allograft rejection. There was significant correlation
      with this diagnosis and the demonstration of IL2R on infiltrating lymphocytes.
      The CCTT system of grading correlated better with the presence of IL2R and the
      confirmed diagnosis of acute allograft rejection. The immunohistochemical
      demonstration of IL2R is a useful adjunct in the evaluation of biopsies suspected
      to show changes of acute cellular rejection. Since IL2 expression reflects the
      relative proportion of activated lymphocytes in the cellular infiltrate, it is
      proposed that the degree of IL2 expression may reflect the response of the use of
      monoclonal antibodies (Humanised/Chimaerised) as anti rejection therapy.

PMID- 16625965
TI  - Significance of AgNOR score in benign and malignant soft tissue tumours.
AB  - AgNOR staining was employed on FNAC and histopathological sections obtained from
      patients with soft tissue tumours. The study comprised of 20 normal appearing
      soft tissues, 74 benign and 36 malignant soft tissue tumours. The slides were
      stained with AgNOR in order to differentiate between benign and malignant soft
      tissue tumours. The mean AgNOR count in normal appearing soft tissues, benign
      lesions and malignant lesions was 1.04+/-0.10 (0.94-1.14), 1.51+/-0.21 (1.1-2.1)
      and 4.96+/-1.33 (2.57-7.21) respectively. The mean AgNOR count was found to be
      higher in benign soft tissue tumours as compared to normal appearing soft tissues
      and the difference was found to be statistically significant. The mean AgNOR
      count in soft tissue sarcomas was found to be higher as compared to both normal
      appearing soft tissues and benign soft tissue tumours and the results were found
      to be statistically significant. The increased AgNOR score in both benign and
      malignant soft tissue tumours as compared to normal appearing soft tissues
      indicates high proliferative activity. Thus AgNOR staining is a simple and useful
      method for estimating tumour cell proliferation thereby differentiating normal
      appearing soft tissues from benign and malignant soft tissue tumours.

PMID- 16625966
TI  - Morphometrical analysis in endometrial hyperplasia: predictive of progression to
      cancer.

PMID- 16625967
TI  - Multiple hydatid cysts of ovary and spleen--a case report.

PMID- 16625968
TI  - Macrofollicular encapsulated papillary thyroid carcinoma--a case report.
AB  - Macrofollicular encapsulated papillary thyroid carcinoma (MEPC) is a rare variant
      of papillary carcinoma of thyroid with a favourable clinical course. It could be
      mistaken for a follicular neoplasm or a hyperplastic nodule. We report
      cytological and histopathological features of this rare variant of papillary
      carcinoma in a 22 year old female with brief review of literature.

PMID- 16625969
TI  - Spontaneous tumour lysis syndrome associated with non-Hodgkin's lymphoma--a case
      report.
AB  - Spontaneous tumour lysis syndrome is characterized by hyperuricemia,
      hyperkalemia, hyperphosphatemia, metabolic acidosis and hypocalcemia, that occur
      even prior to the treatment of a neoplasm. This rare occurrence was encountered
      in a patient with non-Hodgkin's lymphoma (NHL), of follicular cell type.
      Conservative but intensive treatment led to complete resolution. Subsequent
      chemotherapy was well tolerated.

PMID- 16625970
TI  - Inappropriate platelet transfusion in a patient with ethylenediamine tetra-
      acetic acid (EDTA)--induced pseudothrombocytopenia.
AB  - Automated platelet counts in the laboratory may be fictitiously low at times and
      require manual confirmation. Ethylenediaminetetra-acetic acid (EDTA) in few
      patients and healthy individuals can induce platelet aggregation, giving rise to
      a spuriously low automated platelet count. This phenomenon which occurs due to
      the presence of IgG antibodies, if unrecognized, can result in incorrect
      diagnosis and consequent inappropriate treatment. We present a patient who
      received inappropriate platelet transfusion as a result of EDTA induced spurious
      thrombocytopenia.

PMID- 16625971
TI  - Immature mediastinal teratoma--a rare pathology.
AB  - A 9 year old female presented with 8 months history of right sided chest pain and
      respiratory distress. Chest X-ray revealed a large anterior mediastinal mass.
      Histopathology of the mass revealed features of an immature teratoma. The case is
      being presented because of its rare occurrence in the mediastinum.

PMID- 16625972
TI  - Right-sided colonic angiodysplasia in a young patient-a case report.
AB  - The histological diagnosis of angiodysplasia is one of the most difficult
      problems in G.I.T. pathology. These lesions are presumed to be degenerative in
      nature, commonly found in population over 60 years of age and rarely in young
      patients. So, diagnosis of angiodysplasia in this age group is even more
      difficult. We present a case of massive bleeding from colonic angiodysplasia in a
      22-year-old female to increase awareness of this uncommon but potentially life
      threatening cause of lower intestinal bleeding in younger age group.

PMID- 16625973
TI  - Paratesticular papillary serous cystadenocarcinoma--a case report.
AB  - A case of paratesticular papillary serous cystadenocarcinoma in a six year old
      child is presented. The occurrence of these epithelial tumours of the ovarian
      type, in the paratesticular region is extremely rare and only six cases have been
      reported so far. They are thought to arise from Mullerian metaplasia of the
      peritoneal lining of the tunica vaginalis, appendix testis or mullerian remnants
      between the testis and spermatic cord.

PMID- 16625974
TI  - Anti Kell allo-antibody in a thalassaemic.
AB  - We describe a case of incidental detection of anti Kell antibody in a child with
      transfusion dependent thalassaemia. Kell antibody detection may be missed by
      routine indirect antiglobulin test (IAT) crossmatch procedure because of low
      prevalence of Kell antigen in the general population. A false negative result can
      be avoided by using sensitive cross matching techniques and screening cells
      representing antigens in homozygous state, against all clinically significant
      antibodies. A transfusion alert card describing the nature of antibody and future
      transfusion policy should be given to such allo-immunized patients.

PMID- 16625975
TI  - Malignant glomus tumour--a case report.
AB  - Glomus tumours are usually benign neoplasms of glomus bodies. Here we report a
      rare case of malignant glomus tumour of soft tissue. The tumour was 8 cm in size,
      infiltrating deep tissue, with nuclear atypia, high mitotic activity (6/HPF),
      atypical mitosis and showed recurrence, thus fulfilling all the criteria of
      malignancy.

PMID- 16625976
TI  - FNAC of gouty tophi--a case report.
AB  - A 52 yrs old male presented with multiple, painless, firm nodules over
      extremities, which were mimicking benign neoplastic lesion. Fine needle
      aspiration was performed from three such nodules which revealed chalky white
      aspirate. After staining the smears with H&E and Giemsa stains, smears show
      amorphous pink material, needle shaped crystalline structures, many macrophages
      and foreign body type giant cells. A diagnosis of gouty tophi was offered which
      was confirmed by histopathology and serum uric acid level.

PMID- 16625977
TI  - A clinicomicrobiological study on the importance of pseudomonas in nosocomially
      infected ICU patients, with special reference to metallo beta1-lactamase
      production.
AB  - The present study was conducted with a view to assess the burden of pseudomonal
      infection in ICU patients of a tertiary care teaching hospital in Uttaranchal. Of
      the 525 patients selected for the study, during a 1-year period, 60 patients
      developed features of nosocomial infection and among them Pseudomonas was
      isolated from one or more samples in 18 patients. The isolated strains were
      speciated and further characterized for determining their antibiogram and for
      production of beta-lactamase, extended spectrum beta-lactamase and metallo-beta
      lactamase enzymes. Pseudomonas aeruginosa was the commonest species isolated
      (54.54%) and endotracheal suction material showed the highest bacterial yield.
      Polymyxin B was found to be the most effective antibiotic followed by imipenem
      and carbenicillin. Though no strain was found to be producing beta-lactamase and
      extended spectrum beta-lactamase enzymes, a total of 12 strains (54.54%) were
      metallo-beta-lactamase producers. For all the beta lactam antibiotics, excepting
      aztreonam, the metallo-beta-lactamase producers showed more resistance compared
      to the non-producers.

PMID- 16625978
TI  - Cell adherence--a determinant of virulence in Yersinia enterocolitica.
AB  - The adherence of pathogenic bacteria to eukaryotic cells plays a central role in
      their ability to colonize the mucosal epithelial surfaces. The adherence by Y.
      enterocolitica to the mucosal surface of the gut is the initiating event leading
      to penetration of mucosa. Adhesion of 10 probable pathogenic and one non
      pathogenic isolate was studied using ileum and colon epithelial cells of mouse
      for 90 minutes. Adhesion study revealed that isolates of Y. enterocolitica had a
      good adhesive property while non pathogenic showed negligible adherence. All
      isolates showed better adherence to colon epithelial cells. The organism
      continued to be excreted in faeces up to 8-10 days after oral feeding. Adhesion
      positive isolates were found to be virulent when tested in mice for diarrhoea and
      death. Adhesion was found to be thermoregulated.

PMID- 16625979
TI  - Prevalence of anti-cysticercus antibodies in slum, rural and urban populations in
      and around Union territory, Chandigarh.
AB  - A comparative analysis for the prevalence of anti-cysticercus antibodies was
      carried out in urban, rural and slum population in & around Union territory of
      Chandigarh. Prevalence of anti-cysticercus antibodies in different population
      groups was found to be 17.3% with highest prevalence (24%) reported from slum
      areas followed by that of rural areas (20%) and least in the urban organized
      sectors (8%). Only 8% of the seropositive individuals had history suggestive of
      neurocysticercosis. Overall, females showed the highest anti-cysticercus response
      of 20.4%.

PMID- 16625980
TI  - Rubella prevalence and its transmission in children.
AB  - Rubella is a major cause of birth defects among the TORCH group of agents causing
      congenital anomalies. Almost all the symptomatic infected infants have long-term
      neurological sequelae & many asymptomatic infants also develop deafness or
      psychomotor retardation later in life. In India need for rubella prevention &
      control is being recognized. Before formulating any kind of rubella vaccination
      policies, data on the burden of disease is important. Hence the prevalence of
      rubella in children and their transmission was evaluated. Paired sera of 146
      babies with suspected intra uterine infection and their mothers from lower
      socioeconomic strata was tested for IgM antibodies by commercially available
      Enzyme immunoassay (EIA) kits. Congenital Rubella Syndrome (CRS) was confirmed in
      babies presenting with rubella compatible defects with positive IgM antibodies
      against rubella. It was seen that out of 146-paired samples evaluated, 15-paired
      samples (10.27%) were positive for IgM antibodies. The transmission rate of
      rubella virus from mother to child when the mother was infected was around 55.55%
      according to this study. CRS prevalence of 10.27% among symptomatic infants is
      significant as a large majority of rubella infection remains undetected and hence
      the actual burden of the disease may be higher. Since the disease is preventable
      by an effective vaccination, strategies for rubella immunization should be
      developed and enhanced.

PMID- 16625981
TI  - In-vitro evaluation of "piperacillin and tazobactum" combination in a tertiary
      care hospital--a preliminary study.

PMID- 16625982
TI  - Acinetobacter sepsis in neonates.

PMID- 16625983
TI  - Helicobacter pylori eradication prior to initiation of long-term non-steroidal
      anti-inflammatory drug therapy in Chinese patients-a cost-effectiveness analysis.
AB  - BACKGROUND: Recent randomized clinical trials suggested that eradication of
      Helicobacter pylori prior to initiation of non-steroidal anti-inflammatory drug
      (NSAID) therapy would reduce the rate of peptic ulcer disease (PUD). OBJECTIVE:
      To analyze the cost-effectiveness of H. pylori eradication prior to initiation of
      long-term NSAID therapy for prevention of NSAID-induced PUD in a cohort of
      Chinese patients at high risk for PUD. METHODS: Clinical and economic data of 100
      participants from a previously reported clinical trial conducted in Hong Kong
      were analyzed. Patients with a history of peptic ulcers were randomized to 1-week
      omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily
      (eradication group; n = 51) or 1-week omeprazole 20 mg twice daily (omeprazole
      group; n = 49) before initiation of diclofenac 100 mg daily for 6 months. The
      rates of PUD and healthcare utilization for routine follow-up as well as for
      management of symptomatic PUD of the 2 groups were retrieved from medical
      records. RESULTS: The rate of symptomatic ulcers in eradication group and
      omeprazole group were 3.9% and 18%, respectively. The mean direct medical cost of
      the eradication group was significantly lower than that of the omeprazole group
      by 30% (US dollar 797 (95% CI = 685 - 909) versus US dollar 1,128 (95% CI = 879 -
      1,377)) (p = 0.018). The results were robust to variation of all the cost items.
      CONCLUSIONS: H. pylori eradication prior to initiation of NSAID therapy appeared
      to reduce the ulcer rate and mean direct medical cost when compared to no
      eradication for Chinese H. pylori-infected NSAID users at high risk for PUD.

PMID- 16625984
TI  - Modification of pepsinogen I levels and their correlation with gastrointestinal
      injury after administration of dexibuprofen, ibuprofen or diclofenac: a
      randomized, open-label, controlled clinical trial.
AB  - OBJECTIVE: To assess the effect of a 2-week treatment with dexibuprofen, in
      comparison with ibuprofen and diclofenac, on pepsinogen plasma concentrations and
      gastrointestinal mucosa, as well as the correlation of these changes with
      gastrointestinal mucosal injury. METHODS: 60 patients with rheumatologic disease
      in chronic therapy with NSAID, were included. After a 7-day run-in period
      patients were randomly assigned to receive a 14-day treatment with dexibuprofen
      (Group A; Day 1 - 3 = 400 mg t.i.d; Day 4 - 14 = 400 mg b.i.d.), ibuprofen (Group
      B; Day 1 - 3 = 800 mg t.i.d; Day 4 -14 = 800 mg b.i.d.) or diclofenac (Group C;
      Day 1 - 3 = 50 mg t.i.d; Day 4 - 14 = 50 mg b.i.d.). Upper gastrointestinal
      endoscopy (Day 15), capsule-endoscopy (Day 16, 7 patients of each group) and
      determination of pepsinogen plasma concentrations were performed (basal and Day
      15). A semiquantitative scale was designed for the assessment of the
      gastrointestinal mucosa. RESULTS: No differences in plasma pepsinogen were found
      between treatment groups or gastrointestinal injury grades or between basal and
      post-therapy determinations. Dexibuprofen showed gastroduodenal mucosal injury in
      fewer patients (42.1%) than was the case with ibuprofen (5%; p = 0.003) and
      diclofenac (30%; p = N.S.). Dexibuprofen administration was also associated with
      more patients having no intestinal mucosal damage (42.86% vs. 28.7% in the
      diclofenac group and 14.29% in the ibuprofen group; p = 0.0175). The rate of
      clinical adverse events was similar in Groups A, B and C (28%, 38% and 34%).
      CONCLUSIONS: Dexibuprofen showed a lower rate of gastroduodenal and intestinal
      mucosal injury. This effect was not mediated by modifications of plasma
      pepsinogen levels.

PMID- 16625985
TI  - Evaluation of the pharmacokinetic interaction between fluvastatin XL and
      cyclosporine in renal transplant recipients.
AB  - OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and
      extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal
      transplant recipients. METHODS: This was a single-center, open-label study. 17
      renal transplant recipients received their standard cyclosporine therapy (Days 1 
      9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8).
      Blood samples were collected and cyclosporine (whole blood) and fluvastatin
      (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence
      detection, respectively. Pharmacokinetic parameters were calculated using non
      compartment analysis and fluvastatin results were compared with historical
      controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no
      significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of
      fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of
      cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the
      presence of fluvastatin). Co-administration of fluvastatin XL also had no effect
      on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal
      transplant patients. The AUC and Cmax for fluvastatin XL in the presence of
      cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold
      higher compared with historical data for fluvastatin XL alone in healthy
      volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical
      data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340
      ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the
      presence of cyclosporine were also similar to the historical controls.
      Concomitant administration of cyclosporine and fluvastatin XL was well tolerated
      by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and
      cyclosporine do not show clinically relevant pharmacokinetic interactions.

PMID- 16625986
TI  - Plasma pharmacokinetics of desmopressin following sublingual administration: an
      exploratory dose-escalation study in healthy male volunteers.
AB  - OBJECTIVE: Desmopressin is usually administered intranasally in the treatment of
      central diabetes insipidus or nocturnal enuresis. The sublingual administration
      of desmopressin is expected to be an alternative to the intranasal route with
      advantages to children and to patients with allergic rhinitis or chronic
      rhinosinusitis. Therefore, the present study was carried out to explore the time
      versus-concentration profile of desmopressin in plasma after sublingual
      administration to healthy volunteers. SUBJECTS AND METHODS: A total of 16 healthy
      male volunteers were enrolled in this open, exploratory, 1-period, randomized,
      dose-escalation study. Volunteers received a single sublingual dose of either 20,
      40, 80, 160, 240 or 320 microg of desmopressin acetate. Desmopressin plasma
      concentrations were measured over a 12-hour period using a validated
      radioimmunoassay method. Safety and tolerability were assessed simultaneously.
      RESULTS: Plasma concentrations of desmopressin were below the lower limit of
      quantification (LLOQ) of 5 pg/ml for doses lower than 80 microg. For the doses of
      160 - 320 microg the time-versus-concentration profiles were higher than the
      LLOQ. The area under the curve from 0 - 12 h (AUC0-12h) was 54.66 +/- 25.92 pg x
      h/ml after the 160 microg dose, 104.38 +/- 79.10 pg x h/ml following the 240
      microg dose and 133.18 +/- 181.84 pg x h/ml following the 320 microg dose. Given
      the data from previous experiments, the time-versus-concentration profile of
      desmopressin in plasma after a sublingual dose of 240 microg appeared to be in
      the range of previously published data on an intranasal dose of 20 microg.
      Sublingual administration of desmopressin proved to be safe and was well
      tolerated by all volunteers. CONCLUSION: A very high inter-individual variability
      in desmopressin plasma concentrations was detected after sublingual
      administration. A sublingual dose of 240 microg of desmopressin appeared to
      result in a pharmacokinetic profile comparable to 20 microg administered
      intranasally. These data, however, need to be verified in a separate well
      designed prospective clinical study.

PMID- 16625987
TI  - Comparative bioavailability of a generic capsule formulation of the reverse
      transcriptase inhibitor efavirenz and the innovator product.
AB  - OBJECTIVE: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI)
      that has been used successfully for more than a decade to treat human
      immunodeficiency virus (HIV) infection. The objective of the current study was to
      determine the bioequivalence between a generic capsule formulation of efavirenz
      and the innovator product. MATERIAL AND METHODS: A total of 41 healthy subjects
      (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the
      generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva,
      Bristol-Myers Squibb) capsule formulations under fasting conditions in a
      randomized, 2-way crossover study. Multiple blood samples were collected over 72
      hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS
      method. Pharmacokinetic (PK) parameters were calculated using non-compartmental
      methods. RESULTS: Plasma concentrations of efavirenz peaked within 2.5 hours and
      then declined in a multi-exponential manner for both formulations. At 72 hours
      post dose, all plasma concentrations of efavirenz were above the LOQ of the assay
      (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum
      plasma concentrations (Cmax) of efavirenz for the generic capsule formulation
      were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence
      intervals of PK parameters between the two formulations were within 80.0 -
      125.0%, suggesting that the two capsule formulations resulted in similar rate and
      extent of bioavailability under fasting conditions. Adverse events were similar
      in nature and frequency for the two formulations. CONCLUSIONS: Based on the above
      results, the generic capsule formulation of efavirenz developed by Ranbaxy should
      be as effective as the innovator product.

PMID- 16625988
TI  - Effect of food intake on the bioavailability of almotriptan, an antimigraine
      compound, in healthy volunteers: an open, randomized, crossover, single-dose
      clinical trial.
AB  - This open, randomized, crossover, single-dose clinical trial evaluated the
      possible pharmacokinetic interaction between a single oral dose of almotriptan 25
      mg, a 5-HT1B/1D receptor agonist for the acute treatment of migraine, and food
      intake in healthy volunteers. The influence of food intake in the rate and extent
      of almotriptan absorption was evaluated by bioequivalence criteria. Tolerability
      and safety of treatment were also assessed. 16 healthy volunteers (8 men and 8
      women, aged 19-27 years) received a crossed single oral dose of almotriptan 25 mg
      under fasting and fed conditions, separated by a 7-day washout period. The
      treatment given under fasting condition was considered as reference. Plasma
      levels of almotriptan were analyzed using high-performance liquid chromatography
      (HPLC) and UV detection at 227 nm. The 90% confidence intervals (CI) for the
      logarithmically transformed Cmax and AUC0-infinity, values of almotriptan under
      fasting and fed conditions (97.8 - 124% and 102.9 - 108.2%, respectively) fell
      into the predetermined accepted range of 80 - 125%. No statistically significant
      differences in Cmax, tmax, AUC0-infinity, MRT and t1/2 were observed under
      fasting and fed conditions between men and women. Tolerability of treatments was
      good throughout the whole study period. In conclusion, administration of
      almotriptan 25 mg is bioequivalent under fasting and fed conditions in healthy
      men and women. Therefore, it is unlikely that concomitant food intake would
      produce clinially relevant differences in therapeutic effect with almotriptan at
      the dose studied here.

PMID- 16625989
TI  - Levocetirizine in patients with chronic idiopathic urticaria: results of a
      multicenter clinical practice study.

PMID- 16625990
TI  - [Infectious mononucleosis (primary infection with Epstein-Barr virus].

PMID- 16625991
TI  - [Enhancing the therapeutic potential of the physician-patient-relationship].
AB  - The dependence of the patient-doctor-relationship on social change is briefly
      pointed out. The special challenge for the therapeutic relationship patients with
      somatoform disorders give rise to, is thoroughly outlined. The fact that patients
      with somatization are prone to use unconventional therapies is the reason for an
      analysis of the placebo effect. This analytical consideration allows to
      demonstrate that the success of the unconventional medicine relies on
      characteristic healing factors usually hidden in the blackbox placebo. Acqainted
      with such healing factors the science oriented physician may recognize new
      possibilities to improve his therapeutic impact with a kind of supplementary
      placebo effect. Eventually a practical procedure based on modern psychology is
      proposed to deal with patients with somatoform disorders.

PMID- 16625992
TI  - [The diabetic--a difficult patient difficult to treat?].
AB  - After the diagnosis of Diabetes mellitus one third of the children suffer from a
      transient psychological disorder. Diabetic adults have rates of depression
      between 9% and 27% with macrovascular disease and retinopathy as main risk
      factors. Causes of apparent insulin resistance are discussed, particularly the
      omission of insulin to control weight in young women, and the obesity and
      sedentary lifestyle in type 2 diabetics.

PMID- 16625993
TI  - [How effective is treatment of the oldest old?].

PMID- 16625994
TI  - [Psychiatric patient with elevated liver values].

PMID- 16625995
TI  - [Advances in the treatment of breast carcinoma. New therapy schedules with
      astonishing success quotas].

PMID- 16625996
TI  - [For postmenopausal women with hormone-dependent tumors. Aromatase inhibitors are
      the new gold standard].

PMID- 16625997
TI  - [Giving up alcohol is difficult to many. To drink wine inspite of diabetes and
      diet?].

PMID- 16625998
TI  - [All spoke for beginning bronchopneumonia: however antibiotics showed no effect].

PMID- 16625999
TI  - [Sports, travel and rock and roll. What is still possible after myocardial
      infarct?].

PMID- 16626000
TI  - [My comments on complementary medicine. Are they really too negative?].

PMID- 16626001
TI  - [Emergency measures in acute arterial occlusion. Why there are still colleagues
      who do it incorrectly?].

PMID- 16626002
TI  - [Hypertension, hyperlipidemia and cardiac insufficiency in senior citizens are
      problematic conditions. When it comes to the geriatric patient, medical science
      is on shaky ground].

PMID- 16626003
TI  - [Specific aspects of hypertension control in the geriatric patient].
AB  - Hypertensive patients older than 65 obtain greater benefit from antihypertensive
      therapy than do younger patients. The universally accepted values for the
      adjustment of blood pressure--140/90 mmHg--also apply in the case of the elderly.
      Hypertension control in this age group necessitates the taking into account of a
      number of peculiarities, including a tendency for these patients to develop
      postprandial hypotension, and to exhibit a diminishment in thirst, impairment of
      renal function and cognitive performance on the one hand, and an increase in salt
      sensitivity, comorbidity and a need for further medications. With regard to
      medicinal treatment, the basic rule is "start low, go slow", that is, a
      combination approach should be initiated at the lowest possible dose, which can
      then be gradually increased. Medical treatment is supplemented by age-group
      related recommendations for general measures.

PMID- 16626004
TI  - [Cardiac failure in the geriatric patient].
AB  - Cardiac insufficiency is a disease of old age. Analyses of subgroups have showed
      that old patients benefit to a particular extent from therapeutic measures the
      effectiveness of which has been confirmed in numerous studies. In the light of
      this knowledge, it is all the more difficult to understand why this group of
      patients are still not receiving effective treatment. In this area, there is an
      urgent need for improvement. Also difficult to understand is the fact that the
      guidelines for the treatment of chronic cardiac failure issued by the German
      Cardiology Society pay so little attention to cardiovascular research of cardiac
      insufficiency in old age, and thus bear indirect responsibility for the less than
      optimal treatment of this condition, which can be so severe in the old patient.
      These guidelines should contain a section on the peculiarities of cardiac
      insufficiency in high old age.

PMID- 16626005
TI  - [Lowering cholesterol in the elderly--yes, no, or maybe?].
AB  - At the present time, there is no adequate database for the application of statins
      for cholesterol lowering in geriatric patients. According to the current position
      adopted by the IOWiG (Institut fur Qualitat and Wirtschaftlichkeit im
      Gesundheitswesen = institute for quality and economy in health care), the
      usefulness of statins in patients with stable CAD or acute coronary syndrome can
      be affirmed. The National Institute of Clinical Excellence favors the
      administration of statins both in primary and secondary prevention of CAD and
      myocardial infarction, and also as a secondary prevention measure in non-severe
      stroke, PAD, unstable angina pectoris, and following revascularization procedures
      on the coronary arteries. Evidence for the superiority of the statins in patients
      older than 75 is, to date, available only for the indication of CAD in patients
      with elevated LDL cholesterol, but only up to the age of 80 years. Secondary
      prevention with statins leading to multipharmacotherapy must be rejected on
      account of the incalculable risk of side effects and drug interactions.

PMID- 16626006
TI  - [Poisoning by the autumn crocus plant].
AB  - Confirmed cases of poisoning resulting from the ingestion of Colchicum autumnale
      in mistake for Allium ursinum were analysed retrospectively. The study included
      32 patients between 27 and 90 years. The severity of the intoxication was graded
      on the basis of the poisoning severity score (PSS). All the patients developed
      diarrhea and/or vomiting after a latency period of between 2 and 24 h. All those
      patients with a latency of > 9 h suffered only mild poisoning. If the leaves were
      boiled before being eaten, 64% of the patients suffered moderate, severe or fatal
      poisoning; when the leaves were eaten raw, only 33%. It is presumed that heating
      may promote the liberation of colchicines from the plant. Eight of the nine
      patients with severe or fatal poisoning were older than 65 years. A possible
      cause of the more serious course in the elderly may be a decrease in renal
      clearance. In addition, a diminished sense of smell may allow the absence of the
      typical garlic smell and taste of Allium ursinum to go unrecognised.

PMID- 16626007
TI  - [Diagnosis and treatment of hypoglycemia unawareness in type 1 and type 2
      diabetes].
AB  - Hypoglycemia unawareness and the associated condition of hypoglycemia associated
      autonomic failure (HAAF) is a serious acute complication that in the early phase
      often goes undiagnosed, and in the advanced stage is frequently not treated. The
      underlying cause is recurrent episodes of hypoglycemia, and it is seen
      predominantly in patients with type 1 diabetes, but may also occur in type 2
      diabetics with low C-peptide levels. In the etiology a self-protection mechanism
      of the CNS with the maintenance of higher glucose concentrations in the brain
      appears to play a central role. Treatment is formally simple and involves the
      scrupulous avoidance of hypoglycemia for a period of at least 4 weeks. In
      practice, however, this requires a high expenditure of effort, and is not always
      successful. The focus of the present review is on a practical diagnostic and
      therapeutic strategy.

PMID- 16626008
TI  - [Dispute about the Board of Directors. Family physicians take down each other
      reciprocally].

PMID- 16626009
TI  - [Additional fee for family physicians by Barmer Contract. The Court blocks money
      for family physician contract].

PMID- 16626010
TI  - ["Bad feet"].

PMID- 16626011
TI  - [Delayed laparotomies in blunt injuries of the abdomen: incidence rates, causes,
      mortality rates and hospitalization times in a group of 139 operated patients. A
      retrospective study].
AB  - INTRODUCTION: Employment of visualizing methods and achievements of conservative
      treatment methods have a major influence on the management of blunt abdominal
      injuries. The aim of the study is to assess incidence rates of, possibly, delayed
      surgeries and complications. PATIENTS AND METHODS: The authors conducted a
      retrospective analysis in a group of 139 operated patients. A common algorithm
      was followed on their admission. The following parameters were assessed in
      patients operated later than 24 hours following their admission (GROUP A): a
      cause of the delay, a mortality rate and duration of their intensive care unit
      (ICU) hospitalization. The parameters were compared to those of a corresponding
      patient group operated no later than 4 hours after their admission (GROUP B).
      RESULTS: The GROUP A included 17 (12.23%) patients. The delay median was 4 days
      (1-48). The diagnostics failed in 9 (52.94%), the conservative care failed in 8
      (47.06%) subjects. The mortality rate was 29.41%. The GROUP B had significantly
      higher survival rates (p-value 0.0445). There was no statistically significant
      difference in the parameters of the ICU hospitalization duration. CONCLUSION:
      Diagnostic conclusions of visualizing methods, including CT scans, cannot be
      fully relied on in blunt abdominal injuries, mainly in cases of intestinal and
      diaphragmatic injuries. When a conservative treatment is indicated, the patient
      has to be closely monitored while sustaining an active surgical approach.

PMID- 16626012
TI  - [Atypical aneurysms of the superficial femoral artery in a young patient].
AB  - The authors present an unusual case of an urgent aneurysm of the superficial
      femoral artery in a young patient. The case raised a suspicion of a possibility
      of a genetic collagen disorder, primarily of the Marfan's syndrome. Also a
      malignant ethiology of the process was considered. The finding was managed by its
      radical extirpation and the resected part of the superficial femoral artery was
      replaced by a reverse graft of the vena saphaena magna. The original diagnosis of
      the Marfan's syndrome or a malignancy was not confirmed.

PMID- 16626013
TI  - [Lung resection for a non-small cell carcinoma (stage IV) with a permanent
      intracavitary brachytherapy 125I].
AB  - In November 2005, the authors used the lung resection method in combination with
      peroperative brachytherapy125 for a non-small cell carcinoma, for the first time.
      The patient had an adenocarcinoma of the right lung T2N2M0, stage IIIA. During
      the procedure, the team diagnosed advanced stage of the process, the tumor
      originated in the hilus region of the middle lobe with a metastatic spread into
      the superior and inferior lobe. Distant unilateral lymphonodes were infiltrated
      simultaneously. The histological examination confirmed the diagnosis of T2N2M1,
      however, the original classification was re-assessed and changed to stage IV.
      Pneumonectomy with lymphadenectomy of all of the macroscopically detectable
      lymphonodes was completed. The lymphatic drainage sites in the upper and lower
      mediastinum were covered by seeds of a permanent gama emitter 125I with a total
      dose of 100 Gy. The patient recovered with no complications and was discharged on
      the day 8. He was included in the study and will be followed on a regular basis.
      On the authors' opinion, the method of the lung resection with peroperative
      permanent brachytherapy has a potential for decreasing the tumor relaps rates,
      eventually, for improving the patients survival rates and their quality of life.
      The authors will continue their applied research of this serious problematics,
      aiming to confirm or refuse the stated hypothesis.

PMID- 16626014
TI  - [An axillary metastasis as the first sign of the breast carcinoma--a case
      review].
AB  - BACKGROUND: Carcinoma of the breast is the most commonly diagnosed women cancer.
      Less than 1% of the patients diagnosed with breast cancer initially present with
      axillary metastases as their only clinical manifestation. CASUISTIC: We report
      case of 58 years old woman with occult breast carcinoma in which extensive
      axillary node metastasis was the first manifestation. DISCUSSION: Breast cancer
      presenting with axillary metastases and no clinical apparent primary tumour in
      the breast is an uncommon form of stage II or IV of this disease.
      Ultrasonography, mammography, MRI and excisional biopsy are indicated for
      detecting occult primary tumours. The appropriate treatment of the breast after
      an axillary presentation of occult breast carcinoma continues to be a
      controversial issue. Complete axillary lymph node dissection is indicated in all
      patients. As a local treatment of the breast is indicated irradiation of the
      breast or total mastectomy or subcutaneus mastectomy with application of the
      breast prothesis. CONCLUSION: Axillary metastasis is rare first sign of breast
      cancer. Diagnostics of the occult breast carcinoma is difficult. The treatment of
      occult breast carcinoma is still controversial.

PMID- 16626015
TI  - [The rectal carcinoma treatment history].
AB  - The authors demonstrate a history of the rectal carcinoma surgical therapy, based
      on the available literature data or on oral information. Furthermore, they add
      their own experience with treatment of the rectal carcinoma, the disorder, which
      in the Czech Republic and, namely, in the Northern Moravian region, has one of
      the highest worldwide incidence rates.

PMID- 16626016
TI  - [A contribution of the anorectal angle measurement according to Schiessel to
      assessment of the safe distance of the inferior resection line in the rectal
      carcinomas surgical procedures].
AB  - Surgical procedures of the anus for rectal malignancies are amongst the most
      difficult procedures within abdominal surgery. Especially when the tumor is
      located in the middle and distal third of the rectum and the surgeons aim to
      conduct a sphincter-saving procedure, the pre-operative diagnostics is a pre
      requisite for a successful treatment. The authors aim to inform the medical
      community on a non-traditional and rarely used examination method of the
      anorectal angle prior to surgical procedures of the rectal carcinomas.

PMID- 16626017
TI  - [The first case of management of the rectovaginal fistule using transanal
      endocsopic microsurgery].
AB  - The authors present an unusual and, according to the available literature data,
      so far unused method--management of the rectovaginal fistule, using a T.E.M.
      technique (transanal endoscopic microsurgery). In their case-review of a female
      patient, they present advantages of this technique in a case of a rare disorder -
      a benign rectovaginal fistule. All of the following employment of a harmonic
      scalpel in the T.E.M. method, as well as of a tissue adhesive Tissucol and of a
      surgical rectoscope in the vaginal phase of the procedure, deserve attention of
      surgeons and gynaecologists.

PMID- 16626018
TI  - [A partial relaps of a colorectal carcinoma metastatic process following liver
      surgery--a multifactorical study].
AB  - In the period of November 1999 - June 2003 78 patients with colorectal liver
      metastases (CLM) were operated at Department of Surgery, University Hospital in
      Pilsen. In multifactorial analysis there were evaluated these clinical
      parametres: age of patient, sex, localisation of primary tumor, Dukes
      classification, grading, staging and histology of primary tumor, histologicaly
      free resection margin, chemotherapy or actinotherapy after colorectal operation,
      type of liver resection, complications after liver surgery, radicality of liver
      surgery, lateralisation of liver metastatic process, number of metastases, blood
      transfusions, repeated liver surgery, volume of metastases. Kaplan-Meier method
      was used for evaluation of survival rate and disease free interval (DFI).
      Statistical analysis of studied clinical parametres was performed by Log-rank
      test and Wilcoxon test. The medium DFI after liver surgery was 16 months for all
      the patients (range 0-55 months), the medium DFI for patients after radical
      surgery was 18 months. The medium survival time after liver surgery for all the
      patients was 30 months (range 1-57 months), for patients after radical surgery it
      was 32 months, and for patients after palliative surgery the medium disease free
      interval was 29 months (range 5-30 months). The 4-year survival rate after the
      liver surgery was for all the patients 37%. The factors statistically significant
      for a disease free interval after liver surgery were bilaterality of metastatic
      process, the microscopically free resection line, radical surgical treatment
      versus RFA and unilaterality of metastatic process. The authors proved followed
      factors as statistically significant for survival rate: grading of colorectal
      cancer and age of patients. The prediction of early recurrence enables us to
      choose adequate surgical therapy or its extension by oncological therapy. More
      thorough follow up of patients with tendency to early recurrence of CLM helps to
      early diagnosis of relaps and it increases the posssibility of repeated liver
      surgery.

PMID- 16626019
TI  - [Primary tumors of the duodenum and the small intestine in our clinical study
      subjects over a ten-year period].
AB  - The authors are evaluating occurrence of primary tumors of duodenum and small
      intestine during last 10 years (1995-2004) as a retrospective study. 13 patients
      were operated in this period, three of them are presented as case reports. The
      main clinical symptoms were bleeding and obstruction, two patients had no
      symptoms. To define the preoperative diagnosis of this kind of tumors is
      difficult and needs an essential combination of exams.

PMID- 16626020
TI  - [Internal hernias--uncommon causes of the status ileosus].
AB  - Internal hernia is an uncommon cause of acute intestinal obstruction with.
      Preoperative diagnosis of an internal hernia is difficult because of the lack of
      specific signs. Only a few cases of internal hernia have been successfully
      diagnosed, however, most cases (74%) were initially diagnosed as intestinal
      obstructions. Authors present the case of the patient with the history of
      resection of gaster sec. Billroth II with gastroenteroanastomosis. The symptoms
      of the internal hernia were vomiting, abdominal pain and leaded to an emergency
      operation. An incarceration of the bowel retroanastomotic under the Braun
      anastomosis. The obstruction was released by the traction of the bowel and the
      abnormal opening was sutured to prevent recurrence.

PMID- 16626021
TI  - [Do we always have the possibility to treat "lege artis"?].
AB  - The case-history occupies of a case of acute cardiac insufficiency in a patient
      at early postoperative period, who underwent a small surgical operation.
      Apparently the banal operation became the starting mechanism of life threatening
      cardiopulmonary insufficiency. Transthoracic echocardiografic diagnostic process
      not gave us the unambiguous response about a cause of that distressed state. The
      primary clinical consideration of the pulmonary embolization was not ambiguously
      acknowledged, though nor excluded. The clinical had to decided, whether the
      heparinization or the thrombolysing treatment was justified.

PMID- 16626022
TI  - [Acute surgical abdomen--a 2003 overview].

PMID- 16626023
TI  - [Our experience with surgical management of injuries to peripheral nerves of the
      upper extremities].
AB  - OBJECTIVES: The authors present their results of 44 microsurgical procedures of
      47 nerves in 44 patients subjects over a period of 19 years, from 1985 to 2003.
      STUDY GROUP SUBJECTS AND METHODS: 44 patients with injuries to peripheral nerves
      of the upper extremities underwent reconstructions of 47 nerves using
      autotransplants. The procedures effectivity results were analysed using the
      following indicators: the injury to the procedure time, the patient's age, the
      autotransplant length, the injury type, the injury site, the injured nerve type.
      RESULTS: The best results were reached: in young patients up to the age of 20, in
      cases of early operations up to 3 months, in cases when grafts up to 5 cm were
      used. Clean, for instance incision injury, has much better prospects for
      successful nerve graft autotransplantation than others, more complicated injuries
      (e.g. lacerated injury or contusion).

PMID- 16626024
TI  - Polyomaviruses and human diseases.
AB  - Polyomaviruses are small, nonenveloped DNA viruses, which are widespread in
      nature. In immunocompetent hosts, the viruses remain latent after primary
      infection. With few exceptions, illnesses associated with these viruses occur in
      times of immune compromise, especially in conditions that bring about T cell
      deficiency. The human polyomaviruses BKV and JCV are known to cause,
      respectively, hemorrhagic cystitis in recipients of bone marrow transplantation
      and progressive multifocal leukoencephalopathy in immunocompromised patients, for
      example, by HIV infection. Recently, transplant nephropathy due to BKV infection
      has been increasingly recognized as the cause for renal allograft failure.
      Quantitation of polyomavirus DNA in the blood, cerebrospinal fluid, and urine,
      identification of virus laden "decoy cells" in urine, and histopathologic
      demonstration of viral inclusions in the brain parenchyma and renal tubules are
      the applicable diagnostic methods. Genomic sequences of polyomaviruses have been
      reported to be associated with various neoplastic disorders and autoimmune
      conditions. While various antiviral agents have been tried to treat polyomavirus
      related illnesses, current management aims at the modification and/or improvement
      in the hosts' immune status. In this chapter, we provide an overview of
      polyomaviruses and briefly introduce its association with human diseases, which
      will be covered extensively in other chapters by experts in the field.

PMID- 16626025
TI  - Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC
      virus (JCV).
AB  - Although discovered over thirty years ago, many aspects of the epidemiology of
      BKV and JCV in the general population, such as the source of infectious virus and
      the mode of transmission, are still unknown. Primary infection with both BKV and
      JCV is usually asymptomatic, and so age seroprevalence studies have been used to
      indicate infection. BKV commonly infects young children in all parts of the
      world, with the exception of a few very isolated communities, adult
      seroprevalence rates of 65-90% being reached by the age of ten years. In
      contrast, the pattern of JCV infection appears to vary between populations; in
      some anti-JCV antibody is acquired early as for BKV, but in others anti-JCV
      antibody prevalence continues to rise throughout life. This indicates that the
      two viruses are probably transmitted independently and by different routes.
      Whilst BKV DNA is found infrequently in the urine of healthy adults, JCV viruria
      occurs universally, increasing with age, with adult prevalence rates often
      between 20% and 60%. Four antigenic subtypes have been described for BKV and
      eight genotypes are currently recognized for JCV. The latter have been used to
      trace population movements and to reconstruct the population history in various
      communities.

PMID- 16626026
TI  - Phylogenomics and molecular evolution of polyomaviruses.
AB  - We provide in this chapter an overview of the basic steps to reconstruct
      evolutionary relationships through standard phylogeny estimation approaches as
      well as network approaches for sequences more closely related. We discuss the
      importance of sequence alignment, selecting models of evolution, and confidence
      assessment in phylogenetic inference. We also introduce the reader to a variety
      of software packages used for such studies. Finally, we demonstrate these
      approaches throughout using a data set of 33 whole genomes of polyomaviruses. A
      robust phylogeny of these genomes is estimated and phylogenetic relationships
      among the polyomaviruses determined using Bayesian and maximum likelihood
      approaches. Furthermore, population samples of SV40 are used to demonstrate the
      utility of network approaches for closely related sequences. The phylogenetic
      analysis suggested a close relationship among the BK viruses, JC viruses, and
      SV40 with a more distant association with mouse polyomavirus, monkey polymavirus
      (LPV) and then avian polyomavirus (BFDV).

PMID- 16626027
TI  - Virus receptors and tropism.
AB  - Polyomaviruses are small, tumorigenic, nonenveloped viruses that infect several
      different species. Interaction of these viruses with cell surface receptors
      represents the initial step during infection of host cells. This interaction can
      be a major determinant of viral host and tissue tropism. This chapter reviews
      what is currently known about the cellular receptors for each of five
      polyomavirus family members: Mouse polyomavirus (PyV), JC virus (JCV), BK virus
      (BKV), Lymphotropic papovavirus (LPV) and Simian virus 40 (SV40). These
      polyomaviruses serve to illustrate the enormous diversity of virus-cell surface
      interactions and allow us to closely evaluate the role of receptors in their life
      cycles. The contribution of other factors such as transcriptional regulators and
      signaling pathways are also summarized.

PMID- 16626028
TI  - Serological cross reactivity between polyomavirus capsids.
AB  - Multiple methods have been used to measure antibodies to polyomavirus virions. In
      order to have a common method for all polyomaviruses, we developed enzyme
      immunoassays (EIAs) using virus-like-particles (VLPs) produced in the baculovirus
      expression system. We tested serum samples from humans and rhesus macaques in VLP
      based EIAs for the two human polyomaviruses, BK and JC virus, and two nonhuman
      primate polyomaviruses, simian virus 40 (SV40) and lymphotropic polyomavirus
      (LPV). Rhesus sera exhibited low level reactivity to BK and JC, and approximately
      10 and 15% of human sera showed low level reactivity to SV40 and LPV,
      respectively. Competitive inhibition assays with VLP protein demonstrated that
      the reactivity of rhesus sera against BK and JC VLPs was blocked by both SV40 and
      the respective human polyomavirus, indicating that the BK and JC assays were
      detected cross-reacting antibodies. Similarly, the reactivity of the majority of
      human sera to SV40 was blocked by both SV40 and BK or JC, demonstrating that the
      SV40 reactivity of human sera is largely due to cross reacting BK and JC
      antibodies. In contrast, the reactivity of human sera to LPV VLPs was blocked by
      LPV but not by BK or JC, providing serological evidence for an unknown human
      polyomavirus related to LPV. SV40 and LPV VLP-based EIAs and competitive
      inhibition assays with heterologous VLPs provide tools for seroepidemiological
      studies of possible SV40 and LPV-like infections of humans.

PMID- 16626029
TI  - Molecular genetics of the BK virus.
AB  - The BK Virus (BKV) genome is a double-stranded, circular DNA molecule with
      genetic organization similar to other polyomaviruses, and high homology to JC
      Virus (JCV) and SV40. The archetypal form of BKV noncoding regulatory region
      (NCRR) is the infectious form of BKV that replicates in the urothelium and is
      excreted in the urine. Rearranged forms of the NCRR are found in kidney and other
      tissues often in association with disease. BKV strains can be assigned to
      genotype/serotype groups based on sequence variation in the VP1 gene. Sequencing
      of the complete genomes from patient samples will enhance BKV phylogenetic
      studies and identify genotypic differences and naturally occurring mutations in
      BKV that may correlate with incidence and/or severity of a disease. This chapter
      is a review of the molecular genetics of the BK virus in respect to BKV disease.

PMID- 16626030
TI  - Serological diagnosis of human polyomavirus infection.
AB  - Measurement of antibody titres to the human polyomaviruses BK and JC has for many
      years had to rely on Hemagglutination inhibition. In recent years, viral serology
      based on virus-like particles (VLPs) in enzyme immunoassays (EIAs) has become
      widely used for a variety of viruses. We sought to establish a modern method for
      serological diagnosis of BK and JC viruses, by using purified VLPs containing the
      VP1 major capsid proteins. Antibody titres in assays based on VLPs of BKV (strain
      SB) showed no correlation to the titres in similar JCV assays. BKV (SB)
      seropositivity increases rapidly with increasing age of the children and reaches
      a 98 % seroprevalence at 7-9 years of age, whereas JCV seroprevalences increase
      more slowly with increasing age reaching 51 % positivity among children 9-11
      years of age. The antibody levels are almost identical in serial samples taken up
      to 5 years apart, suggesting that both BKV and JCV VLP seropositivitities are
      usually stable over time and can be used to measure cumulative exposure to these
      viruses. Serology using SV40 VLPs showed strong cross-reactivity with human
      polyomaviruses, in particular with BKV strain AS, and establishing a specific VLP
      based serology assay for SV40 required blocking with several hyperimmune sera to
      the human polyomaviruses. SV40-specific seropositivity also increased with
      increasing age of children, reaching 14% seroprevalence among children 7-9 years
      of age, but had limited stability over time in serial samples.

PMID- 16626031
TI  - Human polyomavirus JC and BK persistent infection.
AB  - Primary contact with the human polyomaviruses (HPV) is followed by lifelong
      persistence of viral DNA in its host. The most prominent organs affected are the
      kidney, the Central Nervous System (CNS)and the hematopoietic system. Under
      impairment of immune competence limited activation of virus infection can be
      followed by prolonged virus multiplication, severe destruction of tissue and
      disease. The mechanisms responsible for activation episodes of the asymptomatic
      persistent infection are not understood and questions on cellular localization,
      routes of dissemination of HPV infection and its activation are controversially
      discussed. The type of interaction of HPVs with target organs and patients groups
      is highly differentiated. Organ-specific activation above basic level argues for
      strong dependence on the respective immune states of risk group patients.
      However, since immune impairment generally plays an important role in the
      activation of polyomavirus infection, amplification of virus deoxyribonucleic
      acid (DNA) and activation of virus replication is also a normal event that is
      probably subject to immunomodulation in the healthy individual. It also becomes
      clear that BKV and JCV infection is differentially regulated by mechanisms
      depending on the balance of immune control as well as on organ-specific
      signalling.

PMID- 16626032
TI  - Immunity and autoimmunity induced by polyomaviruses: clinical, experimental and
      theoretical aspects.
AB  - In this chapter, polyomaviruses will be presented in an immunological context.
      Principal observations will be discussed to elucidate humoral and cellular immune
      responses to different species of the polyomaviruses and to individual viral
      structural and regulatory proteins. The role of immune responses towards the
      viruses or their proteins in context of protection against polyomavirus induced
      tumors will be described. One central aspect of this presentation is the ability
      of polyomaviruses, and particularly large T-antigen, to terminate immunological
      tolerance to nucleosomes, DNA and histones. Thus, in the present chapter we will
      focus on clinical, experimental and theoretical aspects of the immunity to
      polyomaviruses.

PMID- 16626033
TI  - The pathobiology of polyomavirus infection in man.
AB  - This article traces the discovery of polyomaviruses and outlines investigations,
      which shed light on potential modes of transmission of this increasingly
      important group of human pathogens. The pathobiology of the virus is summarized
      with particular reference to interactions with host cell receptors, cell entry,
      cytoplasmic trafficking, and targeting of the viral genome to the nucleus. This
      is followed by a discussion of sites of viral latency and factors leading to
      viral reactivation. Finally, we present biochemical mechanisms that could
      potentially explain several key elements of tissue pathology characteristic of
      BKV mediated damage to human kidney.

PMID- 16626034
TI  - Polyomavirus-associated nephropathy in renal transplantation: critical issues of
      screening and management.
AB  - Polyomavirus-associated nephropathy (PVAN) is an emerging disease in renal
      transplant patients with variable prevalence of 1-10% and graft loss up to 80%.
      BK virus (BKV) is the primary etiologic agent, but JC virus (JCV) and possibly
      simian virus SV40 may account for some cases. Intense immunosuppression is viewed
      as the most important risk factor. However, the preferential manifestation in
      renal transplants as compared to other allografts or to autologous kidneys of
      other organ transplants suggests that organ determinants and immunologic factors
      synergize: Renal tubular epithelial cells and their compensatory proliferation to
      restore tubular integrity after immunologic, ischemic or toxic injury may provide
      the critical cellular milieu supporting polyomavirus replication while immune
      control is impaired due to maintenance immunosuppression, anti-rejection
      treatment and HLA-mismatches. Patient determinants (older age, male gender,
      seronegative recipient), and viral factors (genotype, serotype) may have a
      contributory role. The definitive diagnosis of PVAN requires allograft biopsy
      which is, however, challenged by (i) limited sensitivity due to (multi-)focal
      involvement (sampling errors); (ii) varying presentations with cytopathic
      inflammatory and/or fibrotic/scarring patterns; (iii) coexisting acute rejection
      which is difficult to differentiate, but impacts on intervention strategies.
      Screening for polyomavirus replication in the urine and in the plasma complements
      allograft biopsy by high sensitivity and allows for noninvasive monitoring. Thus,
      we suggest a terminology similar to invasive fungal diseases where viruria
      ("decoy cells") defines patients at risk ("possible PVAN") who should be
      evaluated for plasma viral load. Increasing BK viremia (>10,000 copies/mL) or
      urine VP-1 mRNA (>6.5x10(5) copies/ng total RNA) load defines "presumptive PVAN"
      for which an intervention of reducing immunosuppression should be considered even
      if the diagnosis could not be confirmed by allograft biopsy ("definitive PVAN").
      The response to intervention should be monitored using plasma DNA or urine mRNA
      load.

PMID- 16626035
TI  - BK virus and immunosuppressive agents.
AB  - The last decade has witnessed the introduction of several potent
      immunosuppressive agents in the field of transplant medicine. Contemporaneously,
      infection with BK virus (BKV) has emerged as an important complication of
      immunosuppression and an important cause of allograft loss after kidney
      transplantation. Rhandhawa et al reported the first case of BKV associated
      nephropathy (BKVN) in the modern era of transplantation, in 1995. Since then
      there has been a resurgence of interest in the epidemiology, biology and
      pathogenic associations of BKV especially in transplant medicine. Up to 90% of
      adults have serologic evidence of exposure to BKV. However, only 1-5% of normal
      healthy adults excrete the virus in the urine (asymptomatic viruria). Thus, for a
      vast majority of the population, the virus remains perfectly latent and this
      state of latency is of no obvious consequence. Almost all instances of disease by
      the BKV have been seen in immunocompromised patients. In recent years, BKV has
      been associated with nephropathy (BKVN) in about 5% of renal transplant patients.
      Once established, the disease may result in allograft loss in 45-70% of patients.
      Although not proven by any prospective study, BKVN causing allograft failure has
      been linked to immunosuppressive regimens containing tacrolimus or mycophenolate
      mofetil. This is noteworthy, as both these agents have been used increasingly as
      the primary maintenance immunotherapy in solid organ transplantation since their
      introduction around 1990. In addition to the immunosuppressed state, other
      factors like allograft injury have been thought to be involved in the
      pathogenesis of the disease. We believe that reactivation of the BKV from its
      latent state crucially depends on an immunocompromised state but more factors
      than one dictate precipitation of clinical end organ disease. In this Chapter, we
      will discuss the clinical aspects of BKV infection in the renal transplant
      recipient. We will focus on the role of immunosuppression as a seminal factor
      allowing replication of the virus. Not all patients who have replicating BKV go
      on to develop nephropathy: we will discuss other host factors that may constitute
      a 'second hit' allowing replicating BKV to precipitate BKVN. Results of our
      recently concluded prospective study on the issue of current immunosuppressive
      agents in the development of BKVN will be discussed. Finally, based on our
      experience, we will provide some guidelines for early diagnosis and management of
      this disease.

PMID- 16626036
TI  - BK virus infection after non-renal transplantation.
AB  - Infection with BK virus (BKV), a member of the Polyomavirus (PV) family, is
      ubiquitous, with the virus remaining in a latent form in the kidney and urinary
      tract. This infection is usually asymptomatic, but with impairment of the
      cellular immune system the virus can reactivate and lead to tissue damage. In
      recipients of bone marrow and solid organ transplants, PV reactivation can be
      associated with disease in urinary tract and kidneys. BKV was first discovered in
      1971 from the urine of a kidney transplant recipient who had developed ureteral
      stenosis 4 months after transplantation. While much of the subsequent research
      focuses on patients after renal transplantation, we will review PV impact in
      patients after bone marrow transplant (BMT) and those with non-renal solid organ
      transplants.

PMID- 16626037
TI  - Latent and productive polyomavirus infections of renal allografts: morphological,
      clinical, and pathophysiological aspects.
AB  - Polyomavirus allograft nephropathy, also termed BK virus nephropathy (BKN) after
      the main causative agent, the polyoma-BK-virus strain, is a major complication
      following kidney transplantation. BKN is the most common viral infection
      affecting the renal allograft with a reported prevalence of 1% up to 10%. It
      often leads to chronic allograft dysfunction and graft loss. BKN is most likely
      caused by the reactivation of latent BK viruses which, under sustained and
      intensive immunosuppression, enter a replicative/productive cycle. Viral disease,
      i.e., BKN, is typically limited to the kidney transplant. It is histologically
      defined by the presence of intranuclear viral inclusion bodies in epithelial
      cells and severe tubular injury. Virally induced tubular damage is the
      morphological correlate for allograft dysfunction. In this chapter, different
      variants of polyomavirus intranuclear inclusion bodies [types 1 through 4] and
      adjunct techniques [immunohistochemistry, in-situ hybridization, electron
      microscopy and polymerase chain reaction (PCR)] that are used for proper
      characterization of disease are described. Special emphasis is placed on the
      clinical and pathophysiological significance of different histological stages of
      BKN.

PMID- 16626038
TI  - Urine cytology findings of polyomavirus infections.
AB  - Polyomaviruses of the BK- and JC-strains often remain latent within the
      transitional cell layer of the bladder, ureters and the renal pelvis as well as
      in tubular epithelial cells of the kidney. Slight changes in the immune status
      and/or an immunocompromised condition can lead to the (re)activation of latent
      polyomaviruses, especially along the transitional cell layer, resulting in the
      shedding of viral particles and infected cells into the urine. A morphologic sign
      of the (re)activation of polyomaviruses is the detection of typical intranuclear
      viral inclusion bearing epithelial cells, so-called "decoy cells", in the urine.
      Decoy cells often contain polyoma-BK-viruses. The inclusion bearing cells are
      easily identified and quantifiable in routine Papanicolaou stained urine cytology
      specimens. With some experience, decoy cells can also be detected in the
      unstained urinary sediment by phase contrast microscopy. Different morphologic
      variants of decoy cells (types 1 through 4) are described and ancillary
      techniques (immunohistochemistry, electron microscopy (EM), and fluorescence-in
      situ-hybridization (FISH)) for proper identification and characterization are
      discussed. Special emphasis is placed on the clinical significance of the
      detection of decoy cells as a parameter to assess the risk for disease, i.e.,
      polyoma-BK-virus nephropathy (BKN) in kidney transplant recipients. The
      sensitivity and specificity of decoy cells for diagnosing BKN is 99% and 95%,
      respectively, the positive predictive value varies between 27% and more than 90%,
      and the negative predictive value is 99%. The detection of decoy cells is
      compared to other techniques applicable to assess the activation of
      polyomaviruses in the urine (polymerase chain reaction (PCR) and EM).

PMID- 16626039
TI  - Diagnosis and treatment of BK virus-associated transplant nephropathy.
AB  - The incidence of polyoma virus infection, particularly that of BK virus (BKV) in
      kidney transplant recipients has been increasing steadily since early 1990s. The
      diagnosis is generally made by a renal allograft biopsy. However the diagnosis
      can sometimes be difficult because of the pathological similarities between BKV
      associated nephropathy (BKVAN) and acute cellular rejection. In addition to the
      difficulties in making a diagnosis, the treatment of BKVAN can also be very
      complex. Reduction in immunosuppression is generally advocated as the initial
      therapeutic option for the management of BKVAN. Despite reduced
      immunosuppression, BKV can persist in the renal allograft and lead to gradual
      loss of kidney function. Hence, new therapeutic options are being evaluated for
      treatment of BKVAN. Cidofovir, an anti-viral agent with known nephrotoxic
      effects, has been successfully used in very low doses to treat patients with
      BKVAN, with serial measurement of the blood and urine BKV load with PCR assays.
      More recently several other agents have also been utilized to treat BKVAN, with
      variable success. This chapter summarizes the current diagnostic modalities and
      therapeutic options for BKVAN.

PMID- 16626040
TI  - Pharmacotherapeutic options for the management of human polyomaviruses.
AB  - Polyomaviruses [BK virus (BKV), JC virus (JCV) and simian virus 40 (SV40)] have
      been known to be associated with diseases in humans for over thirty years. BKV
      associated nephropathy and JCV-induced progressive multifocal leukoencephalopathy
      (PML) were for many years rare diseases occurring only in patients with
      underlying severe impaired immunity. Over the past decade, the use of more potent
      immunosuppression (IS) in transplantation, and the Acquired Immune Deficiency
      Syndrome (AIDS) epidemic, have coincided with a significant increase in the
      prevalence of these viral complications. Prophylactic and therapeutic
      interventions for human polyomavirus diseases are limited by our current
      understanding of polyomaviral pathogenesis. Clinical trials are limited by small
      numbers of patients affected with clinically significant diseases, lack of
      defined risk factors and disease definitions, no proven effective treatment and
      the overall significant morbidity and mortality associated with these diseases.
      This chapter will focus on a review of the current and future research related to
      therapeutic targets and interventions for polyomavirus-associated diseases.

PMID- 16626041
TI  - Leflunomide in solid organ transplantation and polyoma virus infection.

PMID- 16626042
TI  - JC virus can infect human immune and nervous system progenitor cells:
      implications for pathogenesis.
AB  - Recent advances in stem cell biology have called attention to the role these
      cells may play in the pathogenesis of systemic and nervous system diseases.
      Although not capable of indefinite self renewal and pluripotentiality as stem
      cells are, progenitor cells can give rise to cells of different lineages. It is
      infection of these differentiated cells that has traditionally been associated
      with the pathology and symptoms of viral-induced disease. However, neural
      progenitor cells have been shown, in vitro, to be susceptible to infection by
      neurotropic viruses such as the human polyomavirus, JCV, and the lentivirus, HIV
      1. These progenitor cells, which exist during development as well as in the fully
      developed adult brain, could therefore be involved in neuropathogenesis. Morever,
      JCV can also infect progenitor cells of the hematopoietic system, derivatives of
      which have been implicated in the trafficking of virus from the periphery to the
      brain. Interestingly, susceptibility to and molecular regulation of JCV infection
      in hematopoietic cells closely parallels what has been observed in glial cells.
      The biological interaction between the immune and nervous systems that exists in
      the dissemination of virus from periphery to nervous system and the
      susceptibility of both systems to JCV infection provide potential for
      hematopoietic and neural progenitor cell involvement in JCV pathogenesis.

PMID- 16626043
TI  - The polyomavirus, JCV and its involvement in human disease.
AB  - The human neurotropic polyomavirus, JC virus (JCV), is the etiologic agent of
      progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease
      of the central nervous system that occurs mainly in immunosuppressed patients.
      JCV has also been found to be associated with human tumors of the brain and other
      organs. In this chapter, we describe JC virus and its role in human diseases.

PMID- 16626044
TI  - Transforming activities of JC virus early proteins.
AB  - Polyomaviruses, as their name indicates, are viruses capable of inducing a
      variety of tumors in vivo. Members of this family, including the human JC and BK
      viruses (JCV, BKV), and the better characterized mouse polyomavirus and simian
      virus 40 (SV40), are small DNA viruses that commandeer a cell's molecular
      machinery to reproduce themselves. Studies of these virus-host interactions have
      greatly enhanced our understanding of a wide range of phenomena from cellular
      processes (e.g., DNA replication and transcription) to viral oncogenesis. The
      current chapter will focus upon the five known JCV early proteins and the
      contributions each makes to the oncogenic process (transformation) when expressed
      in cultured cells. Where appropriate, gaps in our understanding of JCV protein
      function will be supplanted with information obtained from the study of SV40 and
      BKV.

PMID- 16626045
TI  - Polyomavirus in human cancer development.
AB  - In animal studies, polyoma viruses have been found to be viral agents for
      oncogenesis and to produce a wide range of pathological lesions in experimental
      animals, including a variety of neoplastic tumors. The human polyoma viruses (JCV
      and BKV), along with their simian cousin (SV40), are ubiquitous viruses that are
      primarily associated with progressive multifocal leukoencephalolopathy (PML) and
      hemorrhagic cystitis, respectively, under specific conditions in
      immunocompromized individuals. Currently, polyoma viruses are now undergoing
      increasing scrutiny as possible causes for several human cancers. Evidence has
      been mounting recently that JCV, BKV as well as SV40 are potential oncogenic
      viruses in humans as well.

PMID- 16626046
TI  - BK virus, JC virus and Simian Virus 40 infection in humans, and association with
      human tumors.

PMID- 16626047
TI  - Epidemiologic studies of polyomaviruses and cancer: previous findings,
      methodologic challenges and future directions.
AB  - Polyomavirus infection became the focus of epidemiologic studies of cancer
      several decades ago, soon after the discovery of simian virus 40 (SV40) in 1960
      and its ability to induce tumors in experimentally infected animals in 1961.
      Between 1963 and 2003, eight case-control and eleven cohort studies investigated
      the possible associations between polyomavirus infection and multiple types of
      cancer, including lymphoma, brain tumors, and mesothelioma. Two of these studies
      included measures of infection with the human polyomaviruses, JC virus and BK
      virus. Overall, the results from these studies were mostly null, although
      limitations in study design and exposure assessment complicate their
      interpretation. This chapter includes a review of results from previous
      epidemiologic studies of polyomavirus infection and human cancer, discussion of
      the methodologic challenges in study design, and proposed future directions for
      epidemiologic research.

PMID- 16626048
TI  - The geometry of education: patterns for growth.

PMID- 16626049
TI  - Surgical approaches to the craniocervical junction for the resection of
      chordomas.

PMID- 16626050
TI  - Exploring the limits of survivability: rational indications for decompressive
      craniectomy and resection of cerebral contusions in adults.

PMID- 16626051
TI  - Application of endoscopy to third ventricular tumors.

PMID- 16626052
TI  - Special lecture: glial reactivity after damage: implications for scar formation
      and neuronal recovery.

PMID- 16626053
TI  - CNS Internet tools and neurosurgery.
AB  - The CNS has developed a collection of online tools for the benefit of the public
      and the neurosurgical community. The CNS website, CNS PA, and SANS Wired all
      facilitate information access, communication, and education. Each of these
      applications takes advantage of the power of the Internet as a high-speed,
      asynchronous digital data storage and retrieval system. The CNS has designed and
      compiled these features with the objective of making these tools an easily
      accessible and integral part of neurosurgical education and practice.

PMID- 16626054
TI  - Honored guest presentation: craniocervical developmental anatomy and its
      implications.

PMID- 16626055
TI  - New developments in the surgical management of spinal cord compression caused by
      metastatic tumor.

PMID- 16626056
TI  - Intracranial atherosclerotic disease: common, dangerous, and treatable.

PMID- 16626057
TI  - Intramedullary spinal cord tumors: molecular insights and surgical innovation.

PMID- 16626058
TI  - Accuray, incorporated: a neurosurgical business case study.

PMID- 16626059
TI  - Human embryonic stem cells: hype or hope?

PMID- 16626060
TI  - Modeling and preclinical trials for gliomas.

PMID- 16626061
TI  - Pituitary adenomas and craniopharyngiomas.

PMID- 16626062
TI  - Keyhole surgery in the treatment of sellar region tumors.

PMID- 16626063
TI  - Hydrocephalus: new theories and new shunts?

PMID- 16626064
TI  - Neurostimulation for epilepsy, including a pilot study of anterior nucleus
      stimulation.

PMID- 16626065
TI  - Intrinsic optical signal imaging of normal and abnormal physiology in animals and
      humans--seeing the invisible.

PMID- 16626066
TI  - Honored guest presentation: conception to implication: craniocervical junction
      database and treatment algorithm.

PMID- 16626067
TI  - Advances in biomaterials that led to the artificial disc.

PMID- 16626068
TI  - Fractures of the upper thoracic spine: approaches and surgical management.
AB  - Management of upper thoracic spinal fractures continues to be a challenging task
      for spinal surgeons. Appropriate treatment depends on a variety of factors,
      including the nature of the fracture, the need for neural decompression, and the
      need for spinal stabilization. A number of surgical approaches have been
      developed to address these lesions. Each approach carries its own inherent
      advantages and disadvantages and an understanding of each is required to optimize
      the treatment of any individual patient. As our surgical experience and expertise
      continues to grow in the field of minimally invasive surgery, these techniques
      and novel approaches will provide alternatives for our patients that will
      maintain the current quality of care but minimize surgical trauma and improve
      recovery times.

PMID- 16626069
TI  - Neurosurgery at the crossroads: integrated multidisciplinary management of 449
      patients with brain arteriovenous malformations.

PMID- 16626070
TI  - Treatment of spinal vascular malformations: an integrated approach.

PMID- 16626071
TI  - Surgery for Parkinson's disease: integration of neurology and neurosurgery.

PMID- 16626072
TI  - Biomechanical considerations for stabilization of the craniovertebral junction.

PMID- 16626073
TI  - Neurosurgery in Africa.

PMID- 16626074
TI  - Honored guest presentation: surgery at the crossroads: craniocervical neoplasms.

PMID- 16626075
TI  - Emerging indications in stereotactic radiosurgery.

PMID- 16626076
TI  - Multimodality treatment of pituitary adenomas.

PMID- 16626077
TI  - When it is not cervical radiculopathy: thoracic outlet syndrome--a prospective
      study on diagnosis and treatment.

PMID- 16626078
TI  - Bone graft substitutes for use in spinal fusions.

PMID- 16626079
TI  - Contemporary management of anterior circulation aneurysms.

PMID- 16626080
TI  - Spinal dysraphism: impact of technique and technology on expectations.

PMID- 16626081
TI  - Functional neurosurgery: past, present, and future.

PMID- 16626082
TI  - Decompression, arthrodesis, and arthroplasty: decision making in the surgical
      treatment of lumbar disc disease.

PMID- 16626083
TI  - Treatment of hydrocephalus: mere survival is not enough.

PMID- 16626084
TI  - One size does not fit all: choosing a treatment strategy for trigeminal
      neuralgia.

PMID- 16626085
TI  - Evolution of management strategies for cerebral gliomas: the effects of science
      and technology.

PMID- 16626086
TI  - Honored guest presentation: lifetime experiences and where we are going: Chiari I
      with syringohydromyelia--controversies and development of decision trees.

PMID- 16626087
TI  - The management of traumatic brain injury: the development of guidelines and their
      influence.

PMID- 16626088
TI  - Innovative internal fixation for cervical spine fractures.

PMID- 16626089
TI  - Not your father's lobotomy: psychiatric surgery revisited.

PMID- 16626090
TI  - Surgical management of cervical disc disease: from no fusion to fusion and back
      again.

PMID- 16626091
TI  - Synthes Award for Resident Research on Spinal Cord and Spinal Column Injury:
      granulocyte macrophage colony stimulating factor (GM-CSF) prevents apoptosis and
      improves functional outcome in experimental spinal cord contusion injury.
AB  - OBJECTIVE: Granulocyte macrophage colony stimulating factor (GM-CSF) is a potent
      hematopoietic cytokine, which stimulates stem cell proliferation in the bone
      marrow and inhibits apoptotic cell death in leukocytes. However, the effects of
      GM-CSF in the central nervous system are still unclear. The present study was
      undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and
      improve neurologic function in a spinal cord injury (SCI) model. METHODS: To
      study the effect of GM-CSF on apoptotic neuronal death, we used a staurosporine
      induced neuronal death model in a Neuro 2A (N2A) cell line (in vitro) and in a
      rat SCI model (in vivo). N2A cells were preincubated with GM-CSF for 60 minutes
      before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, we
      pretreated N2A cells with antibodies of the GM-CSF receptor for 60 minutes. SCI
      was made by clip compression. Rats were treated with daily GM-CSF (20 microg/d)
      for 5 days. The number of apoptotic cells in the spinal cord and neurologic
      improvements were checked. RESULTS: GM-CSF pretreatment was found to
      significantly protect N2A cells from apoptosis, and neutralizing antibodies for
      the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the
      rat SCI model, neurologic functions improved significantly in the GM-CSF
      administered group versus the phosphate buffered saline (PBS)-treated control.
      TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick-end labeled) staining showed that GM-CSF administration reduced apoptosis in
      the injured spinal cord. CONCLUSION: Treatment of SCI with GM-CSF showed some
      beneficial effects. Neuronal protection against apoptosis is viewed as a likely
      mechanism underlying the therapeutic effect of GM-CSF in SCI.

PMID- 16626092
TI  - Synthes Award for Resident Research on Brain and Craniofacial Injury: normoxic
      ventilatory resuscitation after controlled cortical impact reduces peroxynitrite
      mediated protein nitration in the hippocampus.
AB  - Resuscitation with 100% ventilatory oxygen is routinely initiated after severe
      traumatic brain injury (TBI). Despite the objective to improve oxygenation of the
      injured brain, there are concerns about the increased production of reactive
      oxygen species (ROS), which can lead to further neuronal damage. 3-nitrotyrosine
      (3-NT), the product of peroxynitrite-meditated tyrosine residue nitration, has
      been used as a marker for ROS-induced oxidative damage to proteins. We
      hypothesized that posttraumatic resuscitation with hyperoxic ventilation with a
      fraction of inspired oxygen (Fio2, 100%) results in increased ROS-induced damage
      to proteins compared with resuscitation with normoxic ventilation or room air
      (Fio2, 21%). Male Sprague-Dawley rats underwent controlled cortical impact (CCI)
      and were resuscitated with either normoxic or hyperoxic ventilation for 1 hour
      after injury (n = 5 per group). Sham-operated control groups received 1 hour of
      normoxic or hyperoxic ventilation without CCI (n = 4-5 per group). Twenty-four
      hours after injury, rats were perfused with fixative, and hippocampi were
      evaluated for levels of 3-NT immunostaining. In a second experiment, for a
      delayed assessment of neuronal survival, another set of rats similarly underwent
      CCI and normoxic or hyperoxic ventilation for 1 hour (n = 4 per group), and a
      sham-operated group was used as a control (n = 4). One week after injury,
      neuronal cell counts and abnormal cell quantification were performed after
      staining with the neuron-specific NeuN antibody. Quantification of 3-NT staining
      revealed significantly increased levels in the ipsilateral hippocampus in the
      hyperoxic CCI group. The normoxic group showed a 51.0% reduction of staining in
      CA1 when compared with those rats resuscitated with hyperoxia and a 50.8%
      reduction in CA3 (both P < 0.05). There was no significant difference in staining
      between the injured normoxic group and the sham-operated groups. In the delayed
      analysis of neuronal survival, although neuronal counts were reduced in the
      hippocampus on the injured side in both injured groups, there was no significant
      difference between hyperoxic and normoxic groups. Similarly, abnormal cell counts
      were not significantly different between groups.

PMID- 16626093
TI  - CSNS Resident Award: healthcare management 101.

PMID- 16626094
TI  - CSNS Young Neurosurgeon Award: acoustic neuroma surgical cost and outcome by
      hospital volume.

PMID- 16626095
TI  - Ronald Tasker Award: nociceptive on- and off-cells in the mesopontine tegmentum.

PMID- 16626096
TI  - Galbraith Award: simvastatin attenuates experimental cerebral vasospasm and
      ameliorates serum markers of neuronal and endothelial injury in patients after
      subarachnoid hemorrhage: a dose-response effect dependent on endothelial nitric
      oxide synthase.

PMID- 16626097
TI  - Stereotactic and Functional Neurosurgery Resident Award: deep brain stimulation
      for generalized dystonia and spasmodic torticollis: rate and extent of
      postoperative improvement.

PMID- 16626098
TI  - Preuss Resident Research Award: bone marrow-derived Flk-1-expressing CD34+ cells
      contribute to the endothelium of tumor vessels in mouse brain.

PMID- 16626099
TI  - Mahaley Clinical Research Award: extent of glioma resection using low-field (0.2
      T) versus high-field (1.5 T) intraoperative MRI and image-guided frameless
      neuronavigation.

PMID- 16626100
TI  - Why patient safety matters.

PMID- 16626101
TI  - A day in the life: how PAs live and work.

PMID- 16626102
TI  - The case of Ms. C.

PMID- 16626103
TI  - Community-acquired MRSA infection: an update.

PMID- 16626104
TI  - Diagnosis and treatment of sarcoidosis.

PMID- 16626105
TI  - Oral health in children overlooked and undertreated.

PMID- 16626106
TI  - ACC/AHA 2005 guideline update: chronic heart failure in the adult.

PMID- 16626107
TI  - GI symptoms in a 34-year-old woman.

PMID- 16626108
TI  - When the treatment becomes the problem.

PMID- 16626109
TI  - Case of the month. Radial styloid fracture with scapholunate ligamentous injury.

PMID- 16626111
TI  - IB-01212, a new cytotoxic cyclodepsipeptide isolated from the marine fungus
      Clonostachys sp. ESNA-A009.
AB  - IB-01212, a new cytotoxic cyclodepsipeptide featuring C2 symmetry, was isolated
      from the mycelium extract of Clonostachys sp. ESNA-A009. The amino acid sequence
      of the compound was determined by spectroscopy techniques. The absolute
      configuration of the amino acids was determined by a combination of the Marfey
      and menthol methods. The structure, which was confirmed by comparison of the
      analytical data for the natural product with a sample obtained by solid-phase
      peptide synthesis, was revealed to be a cyclic dimer formed by two chains of L
      N,N-Me2Leu-L-Ser-L-N-MeLeu-L-N-MePhe bound by the two esters formed between the
      carboxylic acid of the L-N-MePhe and the hydroxyl function of the L-Ser. IB-01212
      is highly cytotoxic to different tumor cell lines.

PMID- 16626110
TI  - Vaccination with human tyrosinase DNA induces antibody responses in dogs with
      advanced melanoma.
AB  - Antitumor immune responses can be elicited in preclinical mouse melanoma models
      using plasmid DNA vaccines encoding xenogeneic melanosomal differentiation
      antigens. We previously reported on a phase I clinical trial of human tyrosinase
      (huTyr) DNA vaccination of 9 dogs with advanced malignant melanoma (World Health
      Organization stages II-IV), in which we demonstrated the safety of the treatment
      and the prolongation of the expected survival time (ST) of subjects as compared
      to historical, stage-matched controls. As a secondary goal of the same study, we
      report here on the induction of tyrosinase-specific antibody responses in three
      of the nine dogs vaccinated with huTyr DNA. The antibodies in two of the three
      responders cross-react with syngeneic canine tyrosinase, demonstrating the
      ability of this vaccine to overcome host immune tolerance and/or ignorance to or
      of "self" antigens. Most interestingly, the onset of antibody induction in these
      three dogs coincides with observed clinical responses and may suggest a means to
      account for their long-term tumor control and survival.

PMID- 16626112
TI  - Total solid-phase synthesis of marine cyclodepsipeptide IB-01212.
AB  - A suitable combination of synthetic design, orthogonal protecting groups and
      coupling reagents was used to complete the first known synthesis of the natural
      marine cyclodepsipeptide IB-01212. The cyclic, symmetric octapeptide contains two
      of each of the following residues: L-N,N-Me2Leu, L-Ser, L-N-MeLeu and L-N-MePhe.
      IB-01212 also features two symmetric ester bonds between the hydroxyl group of
      Ser and the carboxyl function of the N-MePhe. Total solid-phase syntheses of the
      product was performed in parallel via three distinct routes: dimerization of
      heterodetic fragments, linear synthesis, and convergent synthesis. The convergent
      strategy gave the best results in terms of product yield and purity and is
      particularly suitable for the large-scale synthesis of IB-01212 and similar
      peptides.

PMID- 16626113
TI  - Synthesis of a new trans-A2B2 phthalocyanine motif as a building block for
      rodlike phthalocyanine polymers.
AB  - Polyphthalocyanines have potential application in the development of electronic
      materials. One-dimensional polyphthalocyanines are accessible through monomers
      having a trans-A2B2 structure, but the preparation of a truly linear
      polyphthalocyanine is challenging because of limitations imposed by the geometry
      of phthalocyanines and the methodology for their synthesis.
      Benzimidazoporphyrazines are a known class of extra-annulated phthalocyanines. A
      trans-A2B2 benzimidazoporphyrazine is geometrically suitable for the preparation
      of rodlike polymers. A new synthesis of benzimidazoporphyrazines is presented as
      a stepping stone to the synthesis of trans-A2B2 benzimidazoporphyrazines.

PMID- 16626114
TI  - Electron-acceptor-induced isomerization of aryl [6,5] open fulleroids to [6,6]
      closed methanofullerenes and the electrochemical evaluation of their free energy
      difference.
AB  - The thermal and photochemical rearrangements of a series of aryl substituted
      [6,5] open fulleroids to [6,6] closed methanofullerenes are accelerated in the
      presence in of electron acceptors. These [6,5] open fulleroids, facilitated by
      electron acceptors, rearrange thermally by a zwitteronic-type intermediate, while
      the photochemical reactions proceed via an excited-state electron-transfer
      process. The oxidation potentials of these [6,5] open fulleroids and their
      corresponding [6,6] closed methanofullerenes isomers have been evaluated. The
      free energy difference between the [6,5] open fulleroids and their corresponding
      [6,6] closed isomers have been estimated from the difference in their oxidation
      potentials.

PMID- 16626115
TI  - Direct synthesis of esters and amides from unprotected hydroxyaromatic and 
      aliphatic carboxylic acids.
AB  - A facile method for the activation of hydroxy-substituted carboxylic acids using
      benzotriazole chemistry without prior protection of the hydroxy substituents is
      presented. The N-acylbenzotriazole intermediates 2a-g, 6a-d, and 9a-c have been
      used for high-yielding synthesis of both aliphatic (3a-l) and aromatic (7a-h, 10a
      f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a-h and 13a-i
      were obtained using either neat alcohols in neutral microwave conditions or
      nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate
      yields were obtained in the case of aliphatic hydroxy esters 11a,b and
      thiolesters 11e-g from the intermediates 2a-c.

PMID- 16626116
TI  - Efficient microwave access to polysubstituted amidines from
      imidoylbenzotriazoles.
AB  - Microwave reactions of primary and secondary amines with imidoylbenzotriazoles 6a
      w gave diversely substituted amidines 7a-Aa in 76-94% yields. Convenient
      preparations of a variety of amides 5a-Ab (87-96%) and imidoylbenzotriazoles 6a-w
      (56-95%) have also been developed using microwave irradiation under mild
      conditions and short reaction times. These results demonstrate further the
      advantages of microwave synthesis and introduce a new application of
      imidoylbenzotriazoles in the preparation of polysubstituted amidines.

PMID- 16626117
TI  - Syntheses of isochromenes and naphthalenes by electrophilic cyclization of
      acetylenic arenecarboxaldehydes.
AB  - Highly substituted 1H-isochromenes, isobenzofurans, and pyranopyridines can be
      prepared by allowing o-(1-alkynyl)arenecarboxaldehydes and ketones to react with
      I2, ICl, NIS, Br2, NBS, p-O2NC6H4SCl, or PhSeBr and various alcohols or carbon
      based nucleophiles at room temperature. Naphthyl ketones and iodides are also
      readily prepared by the reaction of 2-(1-alkynyl)arenecarboxaldehydes with I2 and
      simple olefins or alkynes.

PMID- 16626118
TI  - NMR method for the determination of solute hydrogen bond acidity.
AB  - It is shown that the difference in the 1H NMR chemical shift of a protic hydrogen
      in DMSO and CDCl3 solvents is directly related to the overall, or summation,
      hydrogen bond acidity for a wide range of solutes. This provides a new and direct
      method of measuring the hydrogen bond acidity. For 54 compounds, the observed
      shifts for 72 protic hydrogens could be correlated to the Abraham solute hydrogen
      bond acidity parameter, A, with a correlation coefficient squared, R2, of 0.938
      and a standard deviation, SD, of 0.054 units in A. A training equation that used
      half the data could predict A values for the remaining data with an average error
      of 0.001 and a standard deviation, SD, of 0.053 units, thus demonstrating the
      predictive power of the method. Unlike any previous method for the determination
      of solute hydrogen bond acidities, the NMR method allows the determination of A
      values for individual protic hydrogens in multifunctional solutes.

PMID- 16626119
TI  - Cyclic phosphate-linked oligosaccharides: synthesis and conformational behavior
      of novel cyclic oligosaccharide analogues.
AB  - CyPLOS (cyclic phosphate-linked oligosaccharides), that is, novel cyclic
      oligosaccharide surrogates, consisting of two, three, and four phenyl-beta-D
      glucopyranoside units, 4,6-linked through stable phosphodiester bonds, were
      prepared by a straightforward and efficient solid-phase protocol. The assembly of
      the linear precursors was achieved by standard phosphoramidite chemistry on an
      automated DNA synthesizer, using a suitably protected 4-phosphoramidite
      derivative of D-glucose as the building block. For the crucial cyclization step a
      phosphotriester methodology was exploited, followed by a mild basic treatment
      releasing the desired cyclic molecules in solution in a highly pure form. The
      cyclic dimer and trimer were also independently prepared by classical solution
      synthesis, basically following the same approach. The solution structural
      preferences of the cyclic dimer and trimer, obtained by detailed NMR analysis,
      are also reported.

PMID- 16626120
TI  - Effect of substituents on activation parameters in aliphatic S(N)2 reactions. A
      DFT study.
AB  - The activation parameters and optimized structures of the reactants and
      transition states in the S(N)2 reactions of substituted pyridines and N,N
      dimethylanilines with methyl iodide were computed at the DFT level in different
      solvents. The measured and calculated deltaG/deltaH/deltaS versus sigma plots
      proved to be linear, and their slopes, the deltadeltaG, deltadeltaH, and
      deltadeltaS reaction constants, were determined. The least solvent-dependent
      deltadeltaG reaction constants can be computed with acceptable accuracy. The
      calculated deltadeltaS data decrease only very slightly with the jointly
      increasing electron-withdrawing effect of the substituents and tightness of the
      transition states. The measured deltadeltaS values are influenced mainly by the
      change of solvation in the reactions, and deltadeltaH is also influenced by the
      reorganization of the solvent. Consequently, the experimental and calculated
      deltadeltaS and deltadeltaH reaction constants may deviate considerably from each
      other. In dipolar aprotic solvents the measured deltadeltaS was less than zero,
      and in protic solvents it was greater than zero. The ordering of the solvent
      molecules around the transition state with increasing charge is increased in the
      former but decreased in the latter media, as compared to the bulk of the
      solvents. The calculated deltaG(o), deltaH(o), and deltaS(o) parameters of the
      unsubstituted compounds agree relatively well with the experimental data for
      reactions of neutral molecules in dipolar aprotic solvents (e.g., XC6H4N(CH3)2 +
      CH3I). On the other hand, the measured and calculated activation parameters may
      show considerable deviations for reactions of ions (e.g., XC5H4NCH3+ + I-) and
      for any reaction in protic solvents.

PMID- 16626121
TI  - Synthesis and optical properties of bis(oligophenyleneethynylenes).
AB  - Bis(oligophenyleneethynylenes) 1-4 were prepared as representative members of a
      new class of potential nonlinear optical materials. The optical properties of 1-4
      were examined for evidence of restricted rotation of the aryl rings when compared
      to their single-strand precursors, which could potentially increase their
      nonlinear response through more effective conjugation. The effect of altering the
      electron density of the terminating functional group of these compounds on their
      properties was also investigated.

PMID- 16626122
TI  - Trichloromethyl chloroformate ("diphosgene"), ClCOOCCl3: structure and
      conformational properties in the gaseous and condensed phases.
AB  - The conformational properties of gaseous trichloromethyl chloroformate (or
      "diphosgene"), ClC(O)OCCl3, have been studied by vibrational spectroscopy [IR
      (gas), IR (matrix), and Raman (liquid)] and quantum chemical calculations (MP2
      and B3LYP with 6-311G basis sets); in addition, the structure of a single crystal
      at low temperature has been determined by X-ray diffraction. ClC(O)OCCl3 exhibits
      only one conformational form having Cs symmetry with a synperiplanar orientation
      of the C-O single bond relative to the C=O double bond. The calculated energy
      difference between the syn and anti forms, 5.73 kcal mol(-1) (B3LYP) or 7.06 kcal
      mol(-1) (MP2), is consistent with the experimental findings for the gas and
      liquid phases. The crystalline solid at 150 K [monoclinic, P2(1)/n, a = 5.5578(5)
      angstroms, b = 14.2895(12) angstroms, c = 8.6246(7) angstroms, beta = 102.443(2)
      degrees, Z = 4] likewise consists only of molecules in the syn form.

PMID- 16626123
TI  - Wide rim urethanes derived from calix[4]arenes: synthesis and self-assembly.
AB  - [reaction: see text] Calix[4]arenes 4, substituted at the wide rim by four N
      tolyl-urethane groups, were synthesized, as well as derivatives 10a,b bearing two
      or three tolyl-urea groups beside of one or two urethane group(s). In contrast to
      tetra-tolyl urea 11, the urethane derivatives do not form hydrogen-bonded,
      dimeric capsules in CDCl3 or benzene-d6, but the dimerization can be induced for
      the triurea 10b by tetraethylammonium cations as guests. The quantitative
      formation of heterodimers is observed for all urethanes 4 and 10a,bin benzene-d6
      in mixtures with a "tetra-loop" tetraurea 14, while "bisloop" tetraureas 13
      require di- or triurea derivatives 10a,b for a clean heterodimerization.

PMID- 16626124
TI  - On the surface-catalyzed reaction between the gases 2,2-dimethylpropanal and
      methanamine. formation of active-site imines.
AB  - The reaction that occurs when vapors of 2,2-dimethylpropanal and methanamine are
      allowed to mix in an infrared gas cell has been examined. The disappearance of
      starting materials and formation of E-imine product, monitored simultaneously, is
      best fit by a process involving wall-associated water. The same or closely
      related processes have been successfully modeled; such processes may also be
      common to pyridoxal-catalyzed transamination and related reactions in biological
      systems.

PMID- 16626125
TI  - Regioselective reductive openings of acetals; mechanistic details and synthesis
      of fluorescently labeled compounds.
AB  - Regioselective reductive openings of mixed phenolic-benzylic acetals, using
      BH3.NMe3-AlCl3, was investigated, and a mechanism where the outcome is directed
      by the electrostatic potential of the two oxygen atoms is presented. The
      regioselective acetal opening was used in the synthesis of a fluorescently
      labeled analogue to antiproliferative xylosides. The fluorescently labeled
      xyloside was tested for uptake, antiproliferative activity, and glycosaminoglycan
      priming in different cell lines. The xyloside was taken up by all cell lines but
      did not initiate glycosaminoglycan biosynthesis.

PMID- 16626126
TI  - 4,6-O-[1-cyano-2-(2-iodophenyl)ethylidene] acetals. improved second-generation
      acetals for the stereoselective formation of beta-D-mannopyranosides and
      regioselective reductive radical fragmentation to beta-D-rhamnopyranosides. scope
      and limitations.
AB  - The [1-cyano-2-(2-iodophenyl)]ethylidene group is introduced as an acetal
      protecting group for carbohydrate thioglycoside donors. The group is easily
      introduced under mild conditions, over short reaction times, and in the presence
      of a wide variety of other protecting groups by the reaction of the 4,6-diol with
      triethyl (2-iodophenyl)orthoacetate and camphorsulfonic acid, followed by
      trimethylsilyl cyanide and boron trifluoride etherate. The new protecting group
      conveys strong beta-selectivity with thiomannoside donors and undergoes a tin
      mediated radical fragmentation to provide high yields of the synthetically
      challenging beta-rhamnopyranosides. The method is also applicable to the
      glucopyranosides when high alpha-selectivity is observed in the coupling reaction
      and alpha-quinovosides are formed selectively in the radical fragmentation step.
      In the galactopyranoside series, beta-glycosides are formed selectively on
      coupling to donors protected by the new system, but the radical fragmentation is
      unselective and gives mixtures of the 4- and 6-deoxy products. Variable
      temperature NMR studies for the glycosylation step, which helped define an
      optimal protocol, are described.

PMID- 16626127
TI  - Highly diastereoselective one-pot synthesis of spiro[cyclopenta[a]indene-2,2'
      indene]diones from 1-indanones and aromatic aldehydes.
AB  - Treatment of 1-indanones with aromatic aldehydes and NaOEt in THF affords complex
      spiropolycyclic compounds through a four-component reaction in which two
      molecules of each starting compound are combined with formation of four new
      carbon-carbon bonds, leading to the elaboration of a new five-membered ring that
      bears five contiguous stereogenic centers with a well-defined relative
      configuration. Different amounts of a minor epimer of the main product are also
      formed. The presence of methoxy substituents in the indanone component and the
      use of aldehydes derived from pi-excedent heterocycles make the dimerization step
      a slower transformation. In these cases, better yields of spirodimers are
      obtained starting from the preformed enones. The reaction seems to take place by
      cross-aldol condensation, dehydration, and dimerization of the thus formed
      enones. The molecular mechanism of the dimerization reaction of enone 5g has been
      studied using DFT methods at the B3LYP/6-31G level. The dimerization takes place
      through a process involving a Michael addition of a carbanion, obtained by
      deprotonation of 5g at the 3-position, to a second molecule of 5g, followed by an
      intramolecular Michael addition in the corresponding intermediate. The final
      protonation of the resulting anion accounts for the formation of the cis-fused
      pentacyclic system.

PMID- 16626128
TI  - Studies in chlorin chemistry. 3. A practical synthesis of c,d-ring symmetric
      chlorins of potential utility in photodynamic therapy.
AB  - [reaction: see text] C,D-ring symmetric chlorins 8 were prepared in 47-85% yield,
      on scales up to several hundred milligrams, by condensation of appropriately
      substituted bis-formyldihydrodipyrrins 6 and dipyrromethane bis-carboxylic acids
      7 in 5% TFA/CH2Cl2 (25 examples). Target chlorins were chosen to systematically
      probe the effect of lipophilic and hydrophilic substituents on tissue
      partitioning and cellular membrane penetration in photodynamic therapy (PDT).

PMID- 16626129
TI  - A strategy for the synthesis of metal bis(2,2':6',2' '-terpyridine)-terminated
      molecular dyads having controlled torsion angles at the central biphenyl linker.
AB  - The synthesis of a series of binuclear complexes comprising bis(2,2':6',2' '
      terpyridine)ruthenium(II) and -osmium(II) centers connected via a geometrically
      constrained 4,4'-biphenyl bridge is described. These compounds have been prepared
      by a "synthesis-at-metal" approach as well as by the conventional method of
      synthesizing the ligand and subsequently attaching the metal center. A
      computational investigation into the behavior of the biphenyl-based bridges has
      been used to provide lowest-energy conformations and to estimate the degree of
      internal fluctuation about the mean torsion angle. It is shown that the length of
      the constraining strap determines both the torsion angle and the internal
      flexibility, with longer straps twisting the biphenyl group so as to relax
      stereochemical interactions between the linking oxygen atoms. Longer straps can
      be formed from poly(ethylene glycol) residues that provide an additional binding
      site for small cations. Electrospray mass spectrometry carried out on solutions
      of these crown ether-like bridges confirmed that Li+, Na+, and K+ ions bind in
      the form of 1:1 complexes. This range of compounds should permit rational
      examination of how the torsion angle affects the rate of through-bond electron
      transfer, electron exchange, and charge shift.

PMID- 16626130
TI  - Coupling-isomerization-N,S-ketene acetal-addition sequences--a three-component
      approach to highly fluorescent pyrrolo[2,3-b]pyridines, [1,8]naphthyridines, and
      pyrido[2,3-b]azepines.
AB  - Annelated 2-amino pyridines such as pyrrolo[2,3-b]pyridines, [1,8]naphthyridines,
      and pyrido[2,3-b]azepines can be synthesized in moderate to good yields in a
      consecutive one-pot three-component process by a coupling-isomerization-enamine
      addition-cyclocondensation sequence of an electron-poor (hetero)aryl halide, a
      terminal propargyl N-tosylamine, and an N,S-ketene acetal. After the coupling
      isomerization sequence, a Diels-Alder reaction with inverse electron demand of
      the intermediate enimine and the N,S-ketene acetal and subsequent aromatization
      furnish annelated 2-amino pyridines 4 that were unambiguously characterized by
      numerous X-ray structure analyses. These heterocycles are highly fluorescent and
      partially pH sensitive, and their electronic structure was studied with
      spectroscopic and computational methods.

PMID- 16626131
TI  - Novel alternative for the N-N bond formation through a PIFA-mediated oxidative
      cyclization and its application to the synthesis of indazol-3-ones.
AB  - The synthesis of a series of N,N'-disubstituted indazolone derivatives starting
      from methyl anthranilates is presented. This general approach features a novel
      and easy way for access to the target N-heterocycles by formation of a new N-N
      single bond. The key cyclization step embraces the formation of an N
      acylnitrenium intermediate, mediated by the hypervalent iodine reagent PIFA, and
      its succeeding intramolecular trapping by the amine moiety under rather mild
      experimental conditions.

PMID- 16626132
TI  - Synthesis of trifluoro- or difluoromethylated olefins by regio- and
      stereocontrolled S(N)2' reactions of gem-difluorinated vinyloxiranes.
AB  - This paper presents a highly stereoselective synthesis of trifluoro- or
      difluoromethylated olefins via an S(N)2' type fluorination or reductions of gem
      difluorinated vinyloxiranes. Their fluorination with HF-Py furnished
      trifluoromethylated allylic alcohols with exclusive E selectivity. On the other
      hand, their reduction with DIBAL-H afforded difluoromethylated E-allylic alcohols
      predominantly, whereas the corresponding Z isomers were formed exclusively by
      treatment with BH3.THF.

PMID- 16626133
TI  - Oxadisilole-fused isobenzofurans. Synthesis and characterization of oxadisilole
      substituted acenes.
AB  - Mono- and bis-oxadisilole-fused isobenzofurans were first synthesized and
      isolated. A series of mono-, bis-, and tris-oxadisilole-substituted acenes were
      then synthesized by benzyne Diels-Alder reactions with the isobenzofurans. The
      photophysical, redox, and thermal properties of these new acenes were
      characterized.

PMID- 16626134
TI  - A new convenient synthesis of propargylic fluorohydrins and 2,5-disubstituted
      furans from fluoropropargyl chloride.
AB  - Fluoropropargyl chloride reacted with carbonyl compounds to give propargylic
      fluorohydrins under mild conditions and in good yields; however, at higher
      temperatures and longer reaction times, 2,5-disubstituted furans are obtained,
      also in good yields. Fluorohydrins can be readily oxidized to alpha-fluoroketones
      and alpha-fluorocarboxylic acids with Jones' reagent.

PMID- 16626135
TI  - Oxidation of cholesterol by a biomimetic oxidant, cetyltrimethylammonium
      dichromate.
AB  - The oxidation of cholesterol by cetyltrimethylammonium dichromate (CTADC) in
      dichloromethane (DCM) yielded 7-dehydrocholesterol, while with addition of acetic
      acid in DCM the product was found to be 5-cholesten-3-one. The kinetics of
      oxidation of cholesterol by CTADC in DCM, in the presence of acid, was
      investigated with change in [acid], [cholesterol], [CTADC], [surfactant],
      temperature, and solvents. The reaction was found to be first order with acetic
      acid and fractional order with CTADC and cholesterol. Michaelis-Menten-type
      kinetics was observed with respect to cholesterol. The solvent isotope effect was
      found to be k(D2O)/k(H2O) = 0.72. The observed experimental data suggest that the
      reaction occurs in reversed micellar system, akin to an enzymatic environment,
      and the reaction path involves the intermediate formation of an ester complex,
      which undergoes decomposition to give the product.

PMID- 16626136
TI  - Peroxyl radical clocks.
AB  - A series of peroxyl radical clocks has been developed and calibrated based on the
      competition between the unimolecular beta-fragmentation (k(beta)) of a peroxyl
      radical and its bimolecular reaction with a hydrogen atom donor (k(H)). These
      clocks are based on either methyl linoleate or allylbenzene and were calibrated
      directly with alpha-tocopherol or methyl linoleate, which have well-established
      rate constants for reaction with peroxyl radicals (k(H-tocopherol) = 3.5 x 10(6)
      M(-1) s(-1), k(H-linoleate) = 62 M(-1) s(-1)). This peroxyl radical clock
      methodology has been successfully applied to determine inhibition and propagation
      rate constants ranging from 10(0) to 10(7) M(-1) s(-1).

PMID- 16626137
TI  - Synthesis of N,N-bis(3-butenyl)amines from 2-azaallyl dication synthetic
      equivalents and conversion to 2,3,6,7-tetrahydroazepines by ring-closing
      metathesis.
AB  - N,N-Bis(3-butenyl)amines can be prepared by the double allylation of either (2
      azaallyl)stannanes or (2-azaallyl)nitriles, both of which thereby act as
      synthetic equivalents to amine alpha,alpha'-dications (2-azaallyl dications).
      Allylmagnesium bromide is the reagent of choice for the double allylation of both
      substrates, although allyllithium also effects the double allylation of (2
      azaallyl)nitriles. Ring-closing metathesis can be performed on the N-protected
      amines, or with in situ protonation, on the free amines to provide 2,3,6,7
      tetrahydroazepines. (2-Azaallyl)nitriles can also be monoallylated to provide N
      (3-butenyl)aminonitriles, whereas the double allylation of (2-azaallyl)stannanes
      cannot be stopped at monoallylation. (2-Azaallyl)silanes undergo monoallylation
      to give N-(3-butenyl)aminosilanes but do not undergo double allylation.

PMID- 16626138
TI  - Zinc- and indium-promoted conjugate addition-cyclization reactions of
      ethenetricarboxylates with propargylamines and alcohol: novel
      methylenepyrrolidine and methylenetetrahydrofuran syntheses.
AB  - A new zinc- and indium-promoted conjugate addition-cyclization reaction to afford
      nitrogen- and oxygen-containing five-membered heterocycles has been developed.
      Reaction of ethenetricarboxylates with propargylamines (1 equiv) in the presence
      of ZnBr2 or InBr3 afforded methylenepyrrolidines in high yields. The
      stoichiometric use of ZnBr2 or InBr3 at room temperature and the catalytic use of
      InBr3-Et3N at 80 degrees C were effective. Reaction of ethenetricarboxylates with
      propargyl alcohol in the presence of ZnBr2 or InBr3 afforded
      methylenetetrahydrofurans.

PMID- 16626139
TI  - Palladium-catalyzed regio- and stereoselective formate reduction of fluorine
      containing allylic mesylates. A new entry for the construction of a tertiary
      carbon attached with a fluoroalkyl group.
AB  - The regioselective palladium-catalyzed formate reduction of gamma-fluoroalkylated
      allylic esters is described. Reduction of the allylic esters under the influence
      of palladium with a monodentate phosphine ligand proceeded preferentially at the
      gamma position, the corresponding reduction products with a fluoroalkyl group at
      the tertiary carbon being afforded in high yields. When the chiral allylic ester
      was employed, complete chirality transfer was observed, leading to the optically
      active materials in high yields.

PMID- 16626140
TI  - Synthesis of aryl ketones or ketimines by palladium-catalyzed arene C-H addition
      to nitriles.
AB  - The unprecedented palladium-catalyzed C-H addition of arenes to nitriles provides
      moderate to excellent yields of aryl ketones or the corresponding hindered
      imines. The addition of a small amount of DMSO increases the yields dramatically.
      Both intermolecular and intramolecular reactions are successful, although the
      intramolecular reactions tend to be more sluggish. This novel chemistry is
      believed to involve palladium-catalyzed C-H activation of the arene by
      electrophilic aromatic substitution, followed by the unusual carbopalladation of
      a nitrile. Similar reactions have been successfully developed employing
      arylboronic acids and nitriles. A concise route to xanthones starting from cheap
      starting materials has been developed employing this synthetic protocol.

PMID- 16626141
TI  - Electric and magnetic properties computed for valence bond structures: is there a
      link between pauling resonance energy and ring current?
AB  - To establish the link between the aromaticity descriptors based on the Pauling
      resonance energy and the molecular properties, the electric (polarizability) and
      magnetic (magnetizability) field response properties have been calculated using
      the valence bond approach for various molecules and their individual Kekule
      resonance structures. The results show that there is no direct relationship
      between the Pauling resonance energy and the properties; the response properties
      are weighted averages of the properties of the individual structures. According
      to the aromaticity criteria based on molecular properties, one-structure benzene
      would be aromatic; thus, concerning molecular properties, spin-coupled bonds do
      not behave like localized bonds in Lewis structures, with which they are usually
      associated.

PMID- 16626142
TI  - Nucleophilic perfluoroalkylation of aldehydes, ketones, imines, disulfides, and
      diselenides.
AB  - Using a procedure analogous to that developed for nucleophilic
      trifluoromethylation, the perfluoroalkyl anion reagents created by mixing C2F5I
      and n-C4F9I with tetrakis(dimethylamino)ethylene (TDAE) were effective in their
      nucleophilic reactions with aldehydes, ketones, imines, disulfides, and
      diselenides. Irradiation proved beneficial in the aldehyde and ketone reactions.

PMID- 16626143
TI  - CpRuCl(PPh3)2-catalyzed cyclopropanation of bicyclic alkenes with tertiary
      propargylic acetates.
AB  - The electron-rich cyclopentadienylruthenium complex CpRuCl(PPh3)2 turns out to be
      an efficient catalyst for the regio- and stereoselective cyclopropanation of
      bicyclic alkenes with tertiary propargylic carboxylates. The reaction provides
      1,2,3-trisubstituted cyclopropanes in high yields as a single stereoisomer
      instead of the expected cyclobutenes via [2 + 2] cycloaddition. Functional groups
      such as ethers, esters, alcohols, phenols, ketones, esters, carboxylic
      anhydrides, nitriles, halides, sulfones, imides, carbamates, and azines are
      tolerated with the catalyzed reaction. An efficient cyclopropanation of
      cyclobutenes was also demonstrated, providing the strained
      bicyclo[2.1.0(1,3)]pentane framework.

PMID- 16626144
TI  - Trisoxazoline/Cu(II)-promoted Kinugasa reaction. Enantioselective synthesis of
      beta-lactams.
AB  - The reactions of nitrones with terminal alkynes, catalyzed by chiral (i)Pr
      trisoxazoline 2a/Cu(ClO4)2.6H2O under air atmosphere, afforded beta-lactams in
      moderate to good yields with up to 85% ee. The diastereoselectivity depends on
      the alkyne. Propiolate gives the trans-isomer as a major product, while the other
      alkynes afford cis-disubstituted lactams predominantly. Copper(II) salt proved to
      be an efficient catalyst precursor for the first time in the Kinugasa reaction,
      and this allowed the reaction to be performed under a practical and convenient
      condition. An appropriate base used in this reaction was essential to control
      both diastereoselectivity and enantioselectivity. Compared with primary and
      tertiary amines, secondary amines gave higher enantioselectivities. The reaction
      scope and limitation as well as the mechanism were also studied.

PMID- 16626145
TI  - Mechanistic investigations into the photochemistry of 4-allyl-tetrazolones in
      solution: a new approach to the synthesis of 3,4-dihydro-pyrimidinones.
AB  - Photolysis (lambda = 254 nm) of 4-allyl-tetrazolones 2a-c was carried out in
      methanol, 1-propanol, 1-hexanol, acetonitrile, and cyclohexane. The sole primary
      photochemical process identified was molecular nitrogen elimination, with
      formation of pyrimidinones 6a-c. Following the primary photocleavage, secondary
      reactions were observed in acetonitrile and cyclohexane, leading to phenyl
      isocyanate (7), aniline (9), and 1-phenylprop-1-enyl-isocyanate (10a). In
      alcoholic solutions, the primary products, 6a-c, remained photostable even under
      extended irradiation, making possible the isolation of 3,4-dihydro-pyrimidinones
      as stable compounds in very high yields. The observed photostability of
      pyrimidinones 6a-c in alcohols is ascribed to the excited state quenching via
      reversible proton transfer, facilitated by the solvent cage stabilization due to
      formation of hydrogen bonds. The viscosity of alcohols is directly related to the
      cage effects observed. The photocleavage of 4-allyl-tetrazolones leads probably
      to a caged triplet radical pair. This hypothesis is confirmed by the solvent
      viscosity effect on the photolysis quantum yields. Additionally, dissolved
      molecular oxygen sensitizes the formation of pyrimidinones, as should be expected
      for a triplet intermediate that can only form the product molecule after T-S
      conversion, which is accelerated by oxygen.

PMID- 16626146
TI  - Nile Red nucleoside: design of a solvatofluorochromic nucleoside as an indicator
      of micropolarity around DNA.
AB  - The fluorophore, Nile Red, effectively works as a polarity-sensitive fluorescence
      probe. We have designed a new nucleoside modified by Nile Red for examining the
      change in the polarity of the microenvironment surrounding DNA. We synthesized a
      Nile Red nucleoside (1), formed by replacing nucleobases with Nile Red, through
      the coupling of a 2-hydroxylated Nile Red derivative and 1,2-dideoxyglycan. This
      nucleoside showed a high solvatofluorochromicity. The fluorescence of 1
      incorporated into DNA was greatly shifted to shorter wavelength by the addition
      of beta-cyclodextrin. The photophysical function of the Nile Red nucleoside will
      be a good optical indicator for monitoring the change in the micropolarity
      properties at a specific site on target sequences with interaction between DNA
      and DNA-binding molecules.

PMID- 16626147
TI  - Solution-phase parallel synthesis with oligoethylene glycol sorting tags.
      Preparation of all four stereoisomers of the hydroxybutenolide fragment of
      murisolin and related acetogenins.
AB  - The principles of the oligoethylene glycol (OEG) mixture synthesis are
      illustrated with the synthesis of all four possible stereoisomers of a
      hydroxybutenolide fragment common to murisolin and many other acetogenins.
      Modified dimethoxybenzyl groups with varying numbers of OEG units (-CH2CH2O-) are
      used to protect alcohols and serve as codes for configurations at two
      stereocenters. The encoded isomers are carried through several steps in a
      sequence of mixing prior to the reaction and then demixing during the separation
      to give individual pure products. A new tagging scheme is introduced in which a
      stereocenter bearing a hydroxy group is given two different tags. These initially
      redundant tags then serve to encode the configuration of another (untagged)
      stereocenter by appropriate pairwise reactions of the tagged precursors. The
      experimental features (reaction, analysis, separation, and characterization) of
      OEG mixture synthesis are detailed and are compared to and contrasted with those
      of fluorous mixture synthesis.

PMID- 16626148
TI  - Unsymmetrical photodimerization of a 9-aminomethylanthracene in the crystalline
      salt.
AB  - By the salt formation with particular nonaromatic dicarboxylic acids, rapid and
      selective photodimerization of 9-(N,N-dimethylaminomethyl)anthracene (1) was
      accomplished in the solid state. For instance, the salt with trans,trans-muconic
      acid or acetylenedicarboxylic acid was led quantitatively to the 9,10:4',1'
      photodimer usy-ht-2, the first example of the unsymmetrical [4+4]
      photodimerization of anthracene in the solid state. The reactions were
      rationalized by the relevant C...C distances between the reacting carbons.

PMID- 16626149
TI  - Lactam synthesis via the intramolecular hydroamidation of alkynes catalyzed by
      palladium complexes.
AB  - The palladium complexes catalyzed intramolecular hydroamidation reaction of
      amidoalkynes gives the corresponding lactams in good to high yields. For example,
      in the presence of 10 mol % of Pd(PPh3)4 and 20 mol % of PhCOOH, the reaction of
      the amidoalkyne 3a in 1,4-dioxane at 100 degrees C proceeded smoothly to give the
      corresponding lactam 4a in 92% yield.

PMID- 16626150
TI  - Single-isomer tetrasubstituted olefins from regioselective and stereospecific
      palladium-catalyzed coupling of beta-chloro-alpha-iodo-alpha,beta-unsaturated
      esters.
AB  - The efficient regioselective and stereospecific synthesis of tetrasubstituted
      olefins using a mild and convenient method is disclosed. 2-Alkynyl esters are
      selectively converted to E-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters
      by exposure to Bu4NI in refluxing dichloroethane. These products are produced
      cleanly, regio- and stereoselectively, and in high yields. Single-isomer
      tetrasubstituted olefins bearing four different carbon substituents are then
      synthesized by sequential palladium-catalyzed coupling reactions. Selectivity
      results from reactivity differences in the intermediate substrates.

PMID- 16626151
TI  - A short and economical synthesis of orthogonally protected C-linked 2-deoxy-2
      acetamido-alpha-D-galactopyranose derivatives.
AB  - A short and high-yielding synthesis has been devised to prepare C-linked 2-deoxy
      2-acetamido-alpha-D-galactopyranose derivative 3. One of the main advantages of
      this approach is that it employs commercially available and inexpensive d
      glucosamine as the starting material. The key steps include a highly
      stereoselective C-allylation followed by epimerization of the C-4 hydroxyl group.
      Building block 3 and orthogonally protected C-linked 2-deoxy-2-acetamido-alpha-D
      galactopyranose derivative 2 were obtained in 44% overall yield (six steps) and
      29% overall yield (eight steps), respectively. This represents a significant
      improvement over previously reported syntheses.

PMID- 16626152
TI  - Synthesis of new sugar-based surfactants and evaluation of their hemolytic
      activities.
AB  - The synthesis of four sugar-based surfactants derived from glucose and (R)-12
      hydroxystearic acid is described. The surfactants have a hydroxy group in the
      hydrophobic part, which is either free or acylated using acetyl chloride,
      hexanoyl chloride, or myristoyl chloride. Three of the synthesized surfactants
      are water-soluble and are evaluated with respect to their CMCs and hemolytic
      activities. The fourth surfactant has limited water solubility and is not further
      included in the study. The investigated surfactants are all hemolytic close to
      their respective CMC indicating that their use in parenteral formulations may be
      limited. Nevertheless, surfactants having the proposed structure appear as
      promising alternatives to existing solubilizing agents for pharmaceutical
      applications.

PMID- 16626153
TI  - Facile synthesis of mono-, di-, and trisubstituted alpha-unbranched hydrazines.
AB  - Methods for the alkylation of di-tert-butyl hydrazine-1,2-dicarboxylate were
      investigated. It was found that under mild conditions mono- or di-substituted
      hydrazine derivatives were obtained in good to excellent yield. Furthermore, it
      was shown that one of the two Boc-groups of the disubstituted derivatives was
      selectively removed by heating, leading to precursors for trisubstituted
      hydrazines.

PMID- 16626154
TI  - Radical-mediated 5-exo-trig cyclizations of 3-silylhepta-1,6-dienes.
AB  - Regioselectivity of the sulfonyl radical mediated 5-exo-trig cyclization of 3
      silylheptadienyl systems 3a-d has been studied. At low temperature, the reaction
      of the sulfonyl radical occurs regioselectively at the allylsilane terminus,
      while a reversal of regioselectivity is observed at 80 degrees C. This general
      trend has been rationalized on the basis of polar effects and radical
      stabilization. Thiyl-mediated radical cyclization of dienes 3a, 3c-d, 7 with
      subsequent sulfur atom transfer was also studied, providing thiabicyclo[3.3.0]
      skeleton in one step with excellent stereocontrol.

PMID- 16626155
TI  - One-pot synthesis of dithiocarbamates accelerated in water.
AB  - Highly efficient one-pot reactions of amines and carbon disulfide with alpha,beta
      unsaturated compounds were carried out in water under a mild and green procedure
      with high yields.

PMID- 16626156
TI  - A simple method of synthesis of (+/-)-2,3-diarylpiperazines and a novel method of
      resolution of (+/-)-2,3-diphenylpiperazine.
AB  - Intramolecular reductive coupling of diimines in the presence of
      Zn/Ti(O(i)Pr)2Cl2 gives the corresponding (+/-)-2,3-diarylpiperazines in 73-83%
      yields with dl/meso ratio >99%:<1%. The (+/-)-2,3-diphenylpiperazine obtained in
      this way was readily resolved partially using L-(+)-tartaric acid, and the
      enantiomeric purity was enhanced to >99% ee via preparation of hydrogen-bonded
      salt aggregates using oxalic acid.

PMID- 16626157
TI  - A convenient multigram synthesis of highly enantioenriched methyl 3
      silylglycidates.
AB  - A multigram scale synthesis of the four stereoisomers of methyl 3-silylglycidates
      (epoxysilanes) with high enantiopurity is described. Key reactions include a
      Sharpless asymmetric epoxidation (SAE) of a trans-vinylsilane and an enzymatic
      resolution of a racemic cis-epoxysilane to establish the desired configurations.
      Few chromatographic separations (5 columns out of 13 steps) are required for
      purification, establishing a convenient reaction sequence for both the trans- and
      cis-isomers.

PMID- 16626158
TI  - Stereoselective synthesis of (+)-goniothalesdiol.
AB  - Stereoselective synthesis of antitumor tetrahydrofuran (+)-goniothalesdiol was
      achieved in high overall yield from (-)-D-tartaric acid. Key features include an
      FeCl3 mediated THF formation with very high selectivity. Synthesis of natural
      gonithalesdiol and its analogue 2,5-bis-epi-goniothalesdiol was achieved from a
      common intermediate.

PMID- 16626159
TI  - Efficient and selective reduction protocols of the 2,2-dimethyl-1,3-benzodioxan-4
      one functional group to readily provide both substituted salicylaldehydes and 2
      hydroxybenzyl alcohols.
AB  - Two complementary procedures have been developed that selectively allow for the
      synthesis of either substituted salicylaldehydes or the corresponding 2
      hydroxylbenzyl alcohols upon treatment of the 2,2-dimethyl-1,3-benzodioxan-4-one
      functional group with DIBAL-H or LAH, respectively.

PMID- 16626160
TI  - New chiral benzothiazine ligand and its use in the synthesis of a chiral
      receptor.
AB  - The development of chiral ligands to direct the course and stereoselectivity of
      many catalytic asymmetric reactions is an important area of interest for many
      research groups. As part of a program examining the chemistry of 2,1
      benzothiazines, we have prepared a new chiral benzothiazine ligand. This ligand
      can be made in as few as three steps from commercially available starting
      materials. Presented herein is the synthesis of the ligand along with the
      synthesis of a chiral molecular receptor that potentially presages a new class of
      chiral molecular tweezers.

PMID- 16626161
TI  - Direct synthesis of polysubstituted quinoline derivatives by InBr3-promoted
      dimerization of 2-ethynylaniline derivatives.
AB  - InBr3 promotes the dimerization of 2-ethynylaniline derivatives containing an
      unsubstituted terminal carbon leading to the production of polysubstituted
      quinoline derivatives in good yield.

PMID- 16626162
TI  - A diastereoselective radical cyclization approach to substituted quinuclidines.
AB  - A new, concise, and flexible approach to novel quinuclidines has been developed,
      which employs a phosphorus hydride mediated radical addition/cyclization reaction
      in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient
      and diastereoselective radical addition/cyclization reaction to give
      trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into
      2,5-disubstituted quinuclidines using S(N)2-type cyclizations. Finally, the
      resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type
      (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have
      structures similar to that of (-)-quinine 1.

PMID- 16626164
TI  - Orphan drug designation and pharmacogenomics: options and opportunities.
AB  - The rapid increase in characterization and understanding of the human genome has
      had a major impact on the development of therapies for rare diseases. The "inborn
      errors of metabolism", which are generally rare diseases, are beginning to
      realize new therapies based on an understanding of disease processes at the
      genetic level. Likewise, an understanding of acquired genetic errors, as seen in
      cancer, is allowing for targeted approaches to therapy that are revolutionizing,
      in many cases, both standards of care and prognosis. Since its inception, the
      Office of Orphan Products Development has been privileged to witness many of the
      successes and also the failures of pharmacogenomics as it relates to rare
      diseases. This approach, from a regulatory standpoint, often calls into question
      even basic assumptions about disease classification. Phenotypically homogeneous
      diseases are more frequently becoming 'subsetted' on the basis of genomics;
      conversely, overlap of therapeutic mechanisms of action is increasingly seen
      across seemingly diverse diseases. With the recent completion of sequencing of
      the human genome, as well as the increasing ease of DNA sequencing, the promise
      and challenge of the pharmacogenetic approach to treatment will be expected to
      play an increasingly important role in development of new therapies for both rare
      and common diseases.

PMID- 16626165
TI  - Immunostimulants revisited: focus on the pharmacology of Ribomunyl.
AB  - Ribomunyl is an immunostimulant that was developed and commercialized in the
      1980s in France and has subsequently been made available in a large number of
      countries. The formulation is composed of proteoglycans from Klebsiella
      pneumoniae and of ribosomes from four of the most commonly encountered bacterial
      strains in recurrent respiratory tract infections. While it is obviously
      difficult to present a thorough summary of all historical data, here we revisit
      the mode of action of this immunostimulant and present a perspective in the
      context of the most recent data and hypotheses on the mechanisms of the
      antibacterial immune responses. We provide various examples of these mechanisms
      in innate immunity (phagocytosis, cell adhesion, dendritic cell maturation, Toll
      like receptors, interferon production, proinflammatory cytokines, activation of
      natural killer cells), as well as in adaptative immunity (polyclonal activation
      of T and B cells, specific immunoglobulin A immune response in an integrated view
      of the mucosal immune system, and T helper type 1/type 2 [Th1/Th2] regulation and
      balance). The effect of this immunostimulant on anti-infectious responses can be
      explained, not only by a stimulation of the antibacterial defense directly
      assumed by innate immunity, but also by a stimulation of the specific
      (adaptative) immune response related to the activation of dendritic cells, of
      which the pivotal role in T-cell differentiation is already well known. This
      supports the potential of bacterial immunostimulants such as Ribomunyl in anti
      infective therapy.

PMID- 16626166
TI  - Efficacy of alemtuzumab in organ transplantation: current clinical status.
AB  - An overview of the past 5 years of clinical renal transplantation would include
      progress in (i) the development of protocols with new induction agents (non
      depleting versus depleting monoclonal and polyclonal antibodies) designed to
      reduce the incidence and severity of acute rejection, (ii) the attempt to reduce
      calcineurin inhibitor short- and long-term nephrotoxicity, and (iii) the attempt
      to reduce immunosuppression overall if an immunoregulatory state ('tolerance')
      against donor alloantigens could be achieved. One such induction agent is the
      humanized anti-CD52 monoclonal antibody alemtuzumab (Campath-1H), which depletes
      T cells (most potently), as well as B cells and other lymphoid subsets, and may
      decrease the dosage or need for concurrent maintenance immunosuppressive agents.

PMID- 16626167
TI  - Cytokine and anti-cytokine therapies for psoriasis and atopic dermatitis.
AB  - Since the discovery of cytokines as key mediators in inflammation, targeting the
      cytokine network has represented a promising therapeutic approach. Psoriasis and
      atopic dermatitis, as T cell-mediated diseases with a strong cytokine component
      and a high unmet medical need, have moved into the focus of experimental
      therapies. Whereas pro-inflammatory cytokines such as tumor necrosis factor (TNF)
      alpha are overexpressed in both diseases, a type 1 cytokine pattern predominates
      in psoriasis and a type 2 cytokine pattern is of pathophysiological importance at
      least in the initial stages of atopic dermatitis. Strategies for intervention
      into the cytokine network have included antagonism of pro-inflammatory cytokines
      (e.g. TNFalpha, interleukin [IL]-1, IL-8, IL-12, IL-18, IL-23) with neutralizing
      antibodies and soluble receptors, application of recombinant cytokines (e.g. IL
      4, IL-10, IL-11, interferon [IFN]-gamma) to shift the cytokine balance, and
      administration of small molecules to modulate cytokine expression or signaling.
      Results from the clinic have led to novel therapeutic options as well as a better
      understanding of the pathophysiology of inflammatory skin diseases. This review
      highlights the various therapeutic strategies, results from the clinic (that are
      in some cases preliminary), and insights that can be drawn from the more advanced
      clinical studies and the use of approved cytokine-directed therapies.

PMID- 16626168
TI  - Neuroproteases in peptide neurotransmission and neurodegenerative diseases:
      applications to drug discovery research.
AB  - The nervous system represents a key area for development of novel therapeutic
      agents for the treatment of neurological and neurodegenerative diseases. Recent
      research has demonstrated the critical importance of neuroproteases for the
      production of specific peptide neurotransmitters and for the production of toxic
      peptides in major neurodegenerative diseases that include Alzheimer, Huntington,
      and Parkinson diseases. This review illustrates the successful criteria that have
      allowed identification of proteases responsible for converting protein precursors
      into active peptide neurotransmitters, consisting of dual cysteine protease and
      subtilisin-like protease pathways in neuroendocrine cells. These peptide
      neurotransmitters are critical regulators of neurologic conditions, including
      analgesia and cognition, and numerous behaviors. Importantly, protease pathways
      also represent prominent mechanisms in neurodegenerative diseases, especially
      Alzheimer, Huntington, and Parkinson diseases. Recent studies have identified
      secretory vesicle cathepsin B as a novel beta-secretase for production of the
      neurotoxic beta-amyloid (Abeta) peptide of Alzheimer disease. Moreover,
      inhibition of cathepsin B reduces Abeta peptide levels in brain. These
      neuroproteases potentially represent new drug targets that should be explored in
      future pharmaceutical research endeavors for drug discovery.

PMID- 16626169
TI  - Peroxisome proliferator-activated receptor-gamma: novel therapeutic target
      linking adiposity, insulin resistance, and atherosclerosis.
AB  - Insulin resistance and obesity is a common health problem in the industrialized
      world. As a result of the availability of high-calorie food and a reduction in
      energy expenditure, maladaptive metabolic processes may interfere with the action
      of insulin and increase susceptibility for the development of atherosclerotic
      cardiovascular diseases. With the advent of peroxisome proliferator-activated
      receptors (PPARs), the mechanisms of this maladaptation and its relationship to
      insulin resistance syndrome components have become less obscure, promising new
      therapeutic approaches for this common problem. In this review we first focus on
      the molecular structure and cellular mechanisms of action of these receptors and
      then discuss how PPAR-gamma, a PPAR isoform, provides a link between adiposity,
      insulin resistance, and atherosclerosis.

PMID- 16626170
TI  - Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia.
AB  - Gemtuzumab ozogamicin (Mylotarg) is a conjugate of a monoclonal antibody and
      calicheamicin, which targets the membrane antigen CD33 in CD33-positive acute
      myeloid leukaemia (AML) and, after cell internalization, releases a derivative of
      the cytotoxic calicheamicin component. In the US, it is approved as monotherapy
      in patients aged>or=60 years with a first relapse of AML who are ineligible for
      other cytotoxic therapy. Monotherapy with gemtuzumab ozogamicin results in
      complete remission (CR) or CR with incomplete platelet recovery (CRp) in
      approximate, equals 25% of adults (including those aged>or=60 years) with CD33
      positive AML in first relapse. Preliminary data indicate a potential role for
      gemtuzumab ozogamicin as a component of induction or consolidation regimens in
      adults and, based on an early study, in the treatment of children with AML,
      although randomized, controlled studies are needed. Serious adverse events,
      notably hepatotoxicity, characterize its tolerability profile, but gemtuzumab
      ozogamicin is comparatively well tolerated by most patients. Gemtuzumab
      ozogamicin is a valuable new treatment option for patients aged>or=60 years with
      CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not
      considered appropriate; patients with a first CR (CR1) of >12 months are likely
      to have the best outcome.

PMID- 16626171
TI  - Adsorption of platinum on the stoichiometric RuO2(110) surface.
AB  - Density functional theory was used to calculate the geometries and electronic
      structures of Pt adsorption on the stoichiometric RuO(2)(110) surface at
      different coverages. The calculated results revealed that the Pt atoms strongly
      adsorb on RuO(2), and two-dimensional growth up to 1.25 ML deposition is
      energetically favorable. At low coverage, the binding between Pt and RuO(2) is
      very strong, accompanied by a significant transfer of electron density from Pt to
      the support and a large downshift of the d-band compared to that of the
      unsupported Pt. At high coverage, a weak interaction of RuO(2) with the Pt
      cluster is observed, and the electronic structure of Pt is only slightly modified
      with respect to that of the unsupported material. Our results suggest that among
      the systems investigated, the RuO(2)-supported Pt at a coverage of 1 ML may
      become one of the best alternatives to pure Pt as a catalyst because it combines
      a high stability and a moderate activity similar to Pt.

PMID- 16626172
TI  - Absence of reptation in the high-temperature folding of the trpzip2 beta-hairpin
      peptide.
AB  - We have carried out extensive all atom explicit solvent simulations of the high
      temperature folding and unfolding of the trpzip2 beta-hairpin peptide and
      examined the resulting trajectories for evidence of folding via a reptation
      mechanism. Over 300 microcanonical simulations of 10 ns each were initiated from
      a Boltzmann ensemble of conformations at 425 K. Though we observed numerous
      folding and unfolding events, no evidence of reptation was found. The diffusional
      dynamics of the peptide are orders of magnitude faster than any observed
      reptation-like motion. Our data suggest that the dominant mechanisms for beta
      hairpin folding under these conditions are hydrophobic collapse and turn
      formation, and that rearrangements occur via significant expansion of the
      polypeptide chain.

PMID- 16626173
TI  - Optimized effective potentials yielding Hartree-Fock energies and densities.
AB  - It is commonly believed that the exchange-only optimized effective potential
      (OEP) method must yield total energies that are above corresponding ground-state
      Hartree-Fock (HF) energies except for one- and two-electron systems. We present a
      simple procedure for constructing local (multiplicative) exchange potentials that
      reproduce exactly the HF energy and density in any finite basis set for any
      number of electrons. For any finite basis set, no matter how large, there exist
      infinitely many such OEPs, which questions their suitability for practical
      applications.

PMID- 16626174
TI  - On the validity range of the Born-Oppenheimer approximation: a semiclassical
      study for all-particle quantization of three-body Coulomb systems.
AB  - The validity range of the Born-Oppenheimer (BO) approximation is studied with
      respect to the variation of the mass (m) of negatively charged particle by
      substituting an electron (e) with muon (mu) and antiproton (p) in hydrogen
      molecule cation. With the use of semiclassical quantization applied to these
      (ppe), (ppmu), and (ppp) under a constrained geometry, we estimate the energy
      difference of the non-BO vibronic ground state from the BO counterpart. It is
      found that the error in the BO approximation scales to the power of 3/2 to the
      mass of negative particles, that is, m(1.5). The origin of this clear-cut
      relation is analyzed based on the original perturbation theory due to Born and
      Oppenheimer, with which we show that the fifth order term proportional to m(5/4)
      is zero and thereby the first correction to the BO approximation should arise
      from the sixth order term that is proportional to m(6/4). Therefore, the validity
      range of the Born-Oppenheimer approximation is wider than that often mistakenly
      claimed to be proportional to m(1/4).

PMID- 16626175
TI  - A convergent multipole expansion for 1,3 and 1,4 Coulomb interactions.
AB  - Traditionally force fields express 1,3 and 1,4 interactions as bonded terms via
      potentials that involve valence and torsion angles, respectively. These
      interactions are not modeled by point charge terms, which are confined to
      electrostatic interactions between more distant atoms (1,n where n>4). Here we
      show that both 1,3 and 1,4 interactions can be described on the same footing as
      1,n (n>4) interactions by a convergent multipole expansion of the Coulomb energy
      of the participating atom pairs. The atomic multipole moments are generated by
      the theory of quantum chemical topology. The procedure to make the multipole
      expansion convergent is based on a "shift procedure" described in earlier work
      [L. Joubert and P. L. A. Popelier, Molec. Phys. 100, 3357 (2002)].

PMID- 16626176
TI  - Short-time dynamics through conical intersections in macrosystems. I. Theory:
      effective-mode formulation.
AB  - The short-time dynamics through a conical intersection of a macrosystem
      comprising a large number of nuclear degrees of freedom (modes) is investigated.
      The macrosystem is decomposed into a "system" part carrying a limited number of
      modes, and an "environment" part. An orthogonal transformation in the
      environment's space is introduced, as a result of which a subset of three
      effective modes can be identified which couple directly to the electronic
      subsystem. Together with the system's modes, these govern the short-time dynamics
      of the overall macrosystem. The remaining environmental modes couple, in turn, to
      the effective modes and become relevant at longer times. In this paper, we
      present the derivation of the effective Hamiltonian, first introduced by
      Cederbaum et al. [Phys. Rev. Lett. 94, 113003 (2005)], and analyze its properties
      in some detail. Several special cases and topological aspects are discussed.

PMID- 16626177
TI  - Short-time dynamics through conical intersections in macrosystems. II.
      Applications.
AB  - We present several numerical applications based upon the effective-mode
      formulation for the short-time dynamics through conical intersections in
      macrosystems, as detailed in the preceding paper and first proposed by Cederbaum
      et al. [Phys. Rev. Lett. 94, 113003 (2005)]. The macrosystem, containing a vast
      number of nuclear degrees of freedom (modes), is decomposed into a system part
      and an environment part. Only three effective environmental modes are needed
      together with the system's modes-to accurately calculate the low resolution
      spectra and the short-time dynamics of the entire macrosystem. For the systems
      discussed here, results are compared to those of a full quantum wave-packet
      propagation. Some rules are extracted to provide general tendencies; these rules
      allow one to understand and predict the dynamical properties in more general
      situations where the exact quantum dynamics of the macrosystem is out of reach.

PMID- 16626178
TI  - Calculation of excitation energies of open-shell molecules with spatially
      degenerate ground states. II. Transformed reference via intermediate
      configuration Kohn-Sham time dependent density functional theory oscillator
      strengths and magnetic circular dichroism C terms.
AB  - An extension of the transformed reference via an intermediate configuration Kohn
      Sham time dependent density functional theory (TRICKS-TDDFT) method for
      calculating the transition energies of molecules with spatially degenerate ground
      states is proposed that enables oscillator strengths to also be evaluated. The
      oscillator strengths are calculated starting from a description of the degenerate
      ground state and the excited states of interest in terms of linear combinations
      of Slater determinants based upon the F-vectors obtained in the TRICKS-TDDFT
      calculation. This approach for calculating oscillator strengths can also be
      applied to several other properties that involve excited states. An example of
      such a property, the C term of magnetic circular dichroism (MCD), is presented.
      The new method is illustrated through example calculations of the absorbance and
      MCD spectra of several octahedral and C(4v) d(5) transition metal complexes. The
      calculated transition energies and oscillator strengths are somewhat too low and
      too high, respectively, but these errors are within the range that would normally
      be expected for TDDFT calculations of this type. The calculations help to resolve
      some previously unexplained problems with the MCD spectra of the C(4v) complexes.

PMID- 16626179
TI  - Excited state geometry optimizations by analytical energy gradient of long-range
      corrected time-dependent density functional theory.
AB  - An analytical excitation energy gradient of long-range corrected time-dependent
      density functional theory (LC-TDDFT) is presented. This is based on a previous
      analytical TDDFT gradient formalism, which avoids solving the coupled-perturbed
      Kohn-Sham equation for each nuclear degree of freedom. In LC-TDDFT, exchange
      interactions are evaluated by combining the short-range part of a DFT exchange
      functional with the long-range part of the Hartree-Fock exchange integral. This
      LC-TDDFT gradient was first examined by calculating the excited state geometries
      and adiabatic excitation energies of small typical molecules and a small
      protonated Schiff base. As a result, we found that long-range interactions play a
      significant role even in valence excited states of small systems. This analytical
      LC-TDDFT gradient was also applied to the investigations of small twisted
      intramolecular charge transfer (TICT) systems. By comparing with calculated ab
      initio multireference perturbation theory and experimental results, we found that
      LC-TDDFT gave much more accurate absorption and fluorescence energies of these
      systems than those of conventional TDDFTs using pure and hybrid functionals. For
      optimized excited state geometries, LC-TDDFT provided fairly different twisting
      and wagging angles of these small TICT systems in comparison with conventional
      TDDFT results.

PMID- 16626180
TI  - Rovibrational spectroscopy calculations of neon dimer using a phase space
      truncated Weyl-Heisenberg wavelet basis.
AB  - In a series of earlier articles [B. Poirier J. Theor. Comput. Chem. 2, 65 (2003);
      B. Poirier and A. Salam J. Chem. Phys. 121, 1690 (2004); B. Poirier and A. Salam
      J. Chem. Phys. 121, 1740 (2004)], a new method was introduced for performing
      exact quantum dynamics calculations in a manner that formally defeats exponential
      scaling with system dimensionality. The method combines an optimally localized,
      orthogonal Weyl-Heisenberg wavelet basis set with a simple phase space truncation
      scheme, and has already been applied to model systems up to 17 degrees of freedom
      (DOF's). In this paper, the approach is applied for the first time to a real
      molecular system (neon dimer), necessitating the development of an efficient
      numerical scheme for representing arbitrary potential energy functions in the
      wavelet representation. All bound rovibrational energy levels of neon dimer are
      computed, using both one DOF radial coordinate calculations and a three DOF
      Cartesian coordinate calculation. Even at such low dimensionalities, the approach
      is found to be competitive with another state-of-the-art method applied to the
      same system [J. Montgomery and B. Poirier J. Chem. Phys. 119, 6609 (2003)].

PMID- 16626181
TI  - MP2 theory investigation on the halides of D6hC36:C36Xn (X=F,Cl,Br; n=2,4,6,12).
AB  - An investigation of C(36)X(n) (X=F,Cl,Br; n=2,4,6,12) formed from the initial
      C(36) fullerene with D(6h) symmetry has been performed using the MP2 theory.
      Their equilibrium structures, reaction energies, strain energies, lowest
      unoccupied molecular orbital-highest occupied molecular orbital (LUMO-HOMO) gap
      energies, and aromaticities have been studied. The calculation results showed
      that those addition reaction were highly exothermic and C(36)X(n) were more
      stable than C(36). Moreover, from the view of thermodynamics it should be
      possible to detect C(36)X(6). The LUMO-HOMO gap energies of C(36)X(n) were higher
      than D(6h)C(36) and the redox characteristics of C(36)X(n) were weaker comparing
      to D(6h)C(36). The analyses of pi-orbital axis vector indicated that the chemical
      reactivity of C(36) was the result of the high strain, and the nucleus
      independent chemical shifts research showed that the stabilities of the C(36)X(6)
      were correlative with the conjugation effect.

PMID- 16626182
TI  - Pulse shaping for optimal control of molecular processes.
AB  - In this paper, a new method is proposed to design optimized control fields with
      desired temporal and/or spectral properties. The method is based on penalizing
      the difference between an optimized field obtained from an iterative scheme and a
      reference field with desired temporal and/or spectral properties. Compared with
      the standard optimal control theory, the current method allows a simple,
      experimentally accessible field be found on the fly; while compared with
      parameter space searching optimization, the iterative nature of this method
      allows automatic exploration of the intrinsic mechanism of the population
      transfer. The method is illustrated by examing the optimal control of vibrational
      excitation of the Cl-O bond with both temporally and spectrally restricted
      pulses.

PMID- 16626183
TI  - Generalized trajectory surface hopping method based on the Zhu-Nakamura theory.
AB  - We present a generalized formulation of the trajectory surface hopping method
      applicable to a general multidimensional system. The method is based on the Zhu
      Nakamura theory of a nonadiabatic transition and therefore includes the treatment
      of classically forbidden hops. The method uses a generalized recipe for the
      conservation of angular momentum after forbidden hops and an approximation for
      determining a nonadiabatic transition direction which is crucial when the
      coupling vector is unavailable. This method also eliminates the need for a
      rigorous location of the seam surface, thereby ensuring its applicability to a
      wide class of chemical systems. In a test calculation, we implement the method
      for the DH(2) (+) system, and it shows a remarkable agreement with the previous
      results of C. Zhu, H. Kamisaka, and H. Nakamura, [J. Chem. Phys. 116, 3234
      (2002)]. We then apply it to a diatomic-in-molecule model system with a conical
      intersection, and the results compare well with exact quantum calculations. The
      successful application to the conical intersection system confirms the
      possibility of directly extending the present method to an arbitrary potential of
      general topology.

PMID- 16626184
TI  - Free energy surfaces from nonequilibrium processes without work measurement.
AB  - Recent developments in statistical mechanics have allowed the estimation of
      equilibrium free energies from the statistics of work measurements during
      processes that drive the system out of equilibrium. Here a different class of
      processes is considered, wherein the system is prepared and released from a
      nonequilibrium state, and no external work is involved during its observation.
      For such "clamp-and-release" processes, a simple strategy for the estimation of
      equilibrium free energies is offered. The method is illustrated with numerical
      simulations and analyzed in the context of tethered single-molecule experiments.

PMID- 16626185
TI  - Multireference Brillouin-Wigner coupled clusters method with noniterative
      perturbative connected triples.
AB  - We developed and implemented the state-specific Brillouin-Wigner coupled cluster
      method with singles, doubles, and noniterative perturbative triples, called MR
      BWCCSD(T), for a general number of closed- and open-shell reference
      configurations. To assess the accuracy of the method, we performed calculations
      of the three lowest electronic states of the oxygen molecule and of the
      automerization barrier of cyclobutadiene. For the oxygen molecule, the results
      were in a good agreement in comparison with those of the iterative MR
      BWCCSDTalpha method. For cyclobutadiene, the effect of connected triples was
      found to be minor, which is in agreement with the previous study by and Balkova
      and Bartlett [J. Chem. Phys. 101, 8972 (1994)].

PMID- 16626186
TI  - Beyond time-dependent exact exchange: the need for long-range correlation.
AB  - In the description of the interaction between electrons beyond the classical
      Hartree picture, bare exchange often yields a leading contribution. Here we
      discuss its effect on optical spectra of solids, comparing three different
      frameworks: time-dependent Hartree-Fock, a recently introduced combined density
      functional and Green's function approaches applied to the bare exchange self
      energy, and time-dependent exact exchange within time-dependent density
      functional theory (TD-EXX). We show that these three approximations give rise to
      identical excitonic effects in solids; these effects are drastically
      overestimated for semiconductors. They are partially compensated by the usual
      overestimation of the quasiparticle band gap within Hartree-Fock. The physics
      that lacks in these approaches can be formulated as screening. We show that the
      introduction of screening in TD-EXX indeed leads to a formulation that is
      equivalent to previously proposed functionals derived from many-body perturbation
      theory. It can be simulated by reducing the long-range part of the Coulomb
      interaction: this produces absorption spectra of semiconductors in good agreement
      with experiment.

PMID- 16626187
TI  - Ab initio electron propagator theory of molecular wires. II. Multiorbital
      terminal description.
AB  - Correlated, ab initio electron propagator methodology may be applied to the
      calculation of electrical current through a molecular wire. A new theoretical
      formalism is developed for the calculation of retarded and advanced Green
      functions in terms of the electron propagator matrix for a bridge molecule. The
      calculation of the current requires integration in a complex half-plane for a
      trace that involves terminal and Green function matrices that may have any rank.
      Because the latter arrays have poles represented by matrices, an alternative
      expression is developed in terms of ordinary poles which are (n-1)-fold
      degenerate or nondegenerate. For an arbitrary number of terminal orbitals, the
      analytical expression for the current is given in terms of pole strengths, poles,
      and terminal matrix elements of the electron propagator, i.e., the parameters
      that are found in the output of numerical calculations.

PMID- 16626188
TI  - Fast and accurate determination of the Wigner rotation matrices in the fast
      multipole method.
AB  - In the rotation based fast multipole method the accurate determination of the
      Wigner rotation matrices is essential. The combination of two recurrence
      relations and the control of the error accumulations allow a very precise
      determination of the Wigner rotation matrices. The recurrence formulas are
      simple, efficient, and numerically stable. The advantages over other recursions
      are documented.

PMID- 16626189
TI  - A rigid-body Newtonian propagation scheme based on instantaneous decomposition
      into rotation and translation blocks.
AB  - The rotation and translation block (RTB) method of Durand et al. [Biopolymers 34,
      759 (1994)] and Tama et al. [Proteins 41, 1 (2000)] provides an appealing way to
      calculate low-frequency normal modes of large biomolecules by restricting the
      space of motions to exclude internal motions of preselected rigid fragments
      within the molecule. These fragments are modeled essentially as rigid bodies and
      the need to calculate high-frequency relative motions of the atoms that form them
      is obviated in a natural way. Here we extend the RTB approach into a method for
      computing the classical (Newtonian) dynamics of a biomolecule, or any large
      molecule, with effective rigid-body constraints applied to a prechosen set of
      internal molecular fragments. This method, to be termed RTB dynamics, is easy to
      implement, conserves the total energy of the system, does not require the
      construction of the matrix of second spatial derivatives of the potential-energy
      function (Hessian matrix), and can be used to compute the classical dynamics of a
      system moving in an arbitrary anharmonic force field. An elementary numerical
      application to signal propagation in the small membrane-bound polypeptide
      gramicidin-A is presented for illustration purposes.

PMID- 16626190
TI  - Exact quantum dynamics study of the O(+)+H2(v=0,j=0)-->OH(+)+H ion-molecule
      reaction and comparison with quasiclassical trajectory calculations.
AB  - The close-coupling hyperspherical (CCH) exact quantum method was used to study
      the title barrierless reaction up to a collision energy (E(T)) of 0.75 eV, and
      the results compared with quasiclassical trajectory (QCT) calculations to
      determine the importance of quantum effects. The CCH integral cross section
      decreased with E(T) and, although the QCT results were in general quite similar
      to the CCH ones, they presented a significant deviation from the CCH data within
      the 0.2-0.6 eV collision energy range, where the QCT method did not correctly
      describe the reaction probability. A very good accord between both methods was
      obtained for the OH(+) vibrational distribution, where no inversion of population
      was found. For the OH(+) rotational distributions, the agreement between the CCH
      and QCT results was not as good as in the vibrational case, but it was
      satisfactory in many conditions. The kk(') angular distribution showed a
      preferential forward character, and the CCH method produced higher forward peaks
      than the QCT one. All the results were interpreted considering the potential
      energy surface and plots of a representative sampling of reactive trajectories.

PMID- 16626191
TI  - Vibrational and rotational energy transfers involving the CH B 2Sigma(-) v=1
      vibrational level in collisions with Ar, CO, and N2O.
AB  - With photolysis-probe technique, we have studied vibrational and rotational
      energy transfers of CH involving the B (2)Sigma(-) (v=1, 0<or=N<or=6, F) state by
      collisions with Ar, CO, and N(2)O. For the vibrational energy transfer (VET)
      measurements, the time-resolved fluorescence of the B-X(0,0) band is monitored
      following the (1,0) band excitation. For the rotational energy transfer (RET)
      measurements, the laser-induced fluorescence of the initially populated state is
      dispersed using a step-scan Fourier transform spectrometer. The time-resolved
      spectra obtained in the nanosecond regime may yield the RET information under a
      single pressure of the collider. The rate constants of intramolecular energy
      transfers are evaluated with simulation of kinetic models. The VET lies in the
      range of 4x10(-12) to 4x10(-11) cm(3) molecule(-1) s(-1), with efficiency
      following the order of Ar<CO<N(2)O, reflecting the average over Boltzmann
      rotational distribution. The RET rates are more rapid by one to two orders of
      magnitude, comparable to the gas kinetic, with the trend of Ar<CO<N(2)O. The
      transfer rates decrease with increasing N and DeltaN, proceeding via the DeltaN=
      1 transitions slightly larger than DeltaN=+1. With the fine-structure labels
      resolved up to N=6, the fine-structure-conserving collisions prevail increasingly
      with increasing N in DeltaN not equal 0. The rate constants for the F(2)-->F(1)
      transitions are larger than the reverse F(1)-->F(2) transitions in DeltaN=0 for
      the Ar and CO collisions. The trend of fine-structure conservation is along the
      order of N(2)O<CO approximately Ar. For the CH-Ar collisions, the fine-structure
      conservation is less pronounced as compared with the v=0 level reported
      previously. In general, the propensity rules obeyed in the v=0 collision with Ar
      are valid in v=1, but the latter case shows a weaker tendency. It might be caused
      by the anisotropy difference of interaction potential when vibrational excitation
      is considered. For the polyatomic collider, the strong long-range dipole-dipole
      interaction may have the chance to vary the rotational orientation to increase
      the fine-structure-changing transitions.

PMID- 16626192
TI  - Theoretical studies on tunneling ionizations of helium atom in intense laser
      fields.
AB  - Our generalized Keldysh theory is applied to the simplest many-electron atom,
      helium atom. For the single ionization (He-->He(+)+e) we derive a compact rate
      formula, which does not contain any series summation or integral and thus is as
      simple as the Ammosov-Delone-Krainov ionization rates. In addition to its
      simplicity, our formula can explicitly show the wavelength dependence.
      Furthermore a simple form of the angular distribution of the photoelectron is
      available. Our compact formula agrees well with both the exact numerical
      calculations [A. Scrinzi et al., Phys. Rev. Lett. 83, 706 (1999)] and
      experimental data [B. Walker et al., Phys. Rev. Lett. 73, 1227 (1994)] in the
      intensity range of I<5x10(15) Wcm(2). In higher intensity regions, we suggest to
      utilize another simple formula which is valid in the tunneling limit.

PMID- 16626193
TI  - The ionic KAl13 molecule: a stepping stone to cluster-assembled materials.
AB  - Theoretical calculations by Khanna and Jena predicted KAl(13) to be an ionically
      bonded, cluster-assembled "diatomic molecule," i.e., K(+)Al(13) (-). We have
      conducted both mass spectral and anion photoelectron spectroscopic studies on
      KAl(n) (-), finding a "dip" at n=13 in both their mass spectrum and in their
      electron affinity versus n trend. While these largely qualitative results are
      consistent with KAl(13) being a salt, they can also be explained in terms of the
      shell model and thus, by themselves, are not conclusive. Quantitative comparisons
      between calculated photodetachment transition energies and the photoelectron
      spectrum of KAl(13) (-), however, allow a strong case to be made for ionic
      bonding in KAl(13). As a prototype for ionic bonding involving intact Al(13) (-)
      subunits, KAl(13) may be a stepping stone toward forming ionic, cluster-assembled
      materials.

PMID- 16626194
TI  - Rate constants for the reactions of CO3- and O3- with SO2 from 300 to 1440 K.
AB  - Rate constants for the reactions of CO(3) (-) and O(3) (-) with SO(2) have been
      measured between 300 and 1440 K in a high temperature flowing afterglow
      apparatus. The CO(3) (-) rate constants near to the collision rate at low
      temperatures and fall by about a factor of 50 with temperature until a broad
      minimum is reached at 900-1300 K. The highest temperature point shows the
      increasing rate constant. Comparison to drift tube data taken in a helium buffer
      shows that total energy controls the reactivity, presumably because the reaction
      goes through a long lived complex even at 1440 K. The reaction of O(3) (-) with
      SO(2) was studied up to 1400 K. The rate constant is collisional until 700 K and
      then decreases with increasing temperature. Rate constants measured at 1300 and
      1400 K appear to show an increase, but that observation is questionable since
      O(3) (-) could not be made cleanly. The O(3) (-) data at 1200 K and below show
      that total energy controls reactivity in that range.

PMID- 16626195
TI  - Differences in electronic properties of fluorinated and trifluoromethylated
      fullerenes revealed by their propensity for dianion formation.
AB  - The cross sections for electron transfer from sodium to C(60)F(n) (-) and
      C(60)(CF(3))(n) (-) anions in 50-keV collisions as a function of the number of
      functional groups n are reported. There are clear differences between derivatives
      of fluorine and trifluoromethyl due to the different electron withdrawing
      properties of F and CF(3). The role of inductive effects and pi electron
      delocalization on the electron affinity is discussed, assuming a correlation
      between the cross section and the electron affinity of the anion.

PMID- 16626196
TI  - Femtosecond degenerate four-wave mixing of carbon disulfide: high-accuracy
      rotational constants.
AB  - Femtosecond degenerate four-wave mixing (fs-DFWM) rotational coherence
      spectroscopy (RCS) has been used to determine the rotational and centrifugal
      distortion constants of the 00 (0)0 ground and 01 (1)0 vibrationally excited
      states of gas-phase CS(2). RCS transients were recorded over the 0-3300 ps
      optical delay range, allowing the observation of 87 recurrences. The fits yield
      rotational constants B(00 (0)0)=3.271 549 2(18) GHz for (12)C(32)S(2) and B(00
      (0)0)=3.175 06(21) GHz for the (12)C(32)S(34)S isotopomer. The rotational
      constants of the degenerate 01 (1)0 bending level of (12)C(32)S(2) are B(01
      (1)0)=3.276 72(40) and 3.279 03(40) GHz for the e and f substrates, respectively.
      These fs-DFWM rotational constants are ten times more accurate than those
      obtained by CO(2) laser/microwave heterodyne measurements and are comparable to
      those obtained by high-resolution Fourier transform infrared spectroscopy. Ab
      initio calculations were performed at two levels, second-order Moller-Plesset
      theory and coupled-cluster singles, doubles, and iterative triples [CCSD(T)]. The
      equilibrium and vibrationally averaged C=S distances were calculated using large
      Dunning basis sets. An extrapolation procedure combining the ab initio rotational
      constants with the experiment yields an equilibrium C=S bond length of 155.448 pm
      to an accuracy of +/-20 fm. The theoretical C=S bond length obtained by a
      complete basis set extrapolation at the CCSD(T) level is r(e)(C=S)=155.579 pm, or
      0.13 pm longer than that in the experiment.

PMID- 16626197
TI  - In search of the germanium halomethylidyne (Ge=C-X; X=F,Cl,Br) free radicals: Ab
      initio studies of their spectroscopic signatures.
AB  - A variety of ab initio methods have been used to calculate the X (2)Pi and A
      (2)Sigma(+) state spectroscopic parameters of the GeCX (X=F,Cl,Br) free radicals.
      The theoretical methods and basis sets were tested on GeCH, for which extensive
      experimental data are available, and found to give predictions sufficiently
      reliable to guide experimental searches for spectra. In all cases, the linear
      Ge=C-X species was found to be the global minimum on the potential energy
      surface, with the bent X-Ge=C ((2)A(')) isomer as a local minimum much higher (62
      36 kcal/mol) in energy. In both the ground and excited states, the GeC moiety is
      very similar to that of GeCH, with a double bond in the lower state and a triple
      bond in the excited state, indicating that halogenation does not radically
      perturb the energetics or structure of germanium methylidyne. Ground state GeCX
      radicals have suitable rotational constants for microwave studies, although they
      suffer from only modest dipole moments. Matrix infrared experiments are most
      likely to detect the nu(1) fundamentals in the 1450-1100 cm(-1) region or the
      nu(3) fundamentals at the transition between the mid- and far-infrared regions.
      We have used the ab initio values for the Renner-Teller parameter, the average
      bending frequency, and the spin-orbit coupling constant to calculate the ground
      state energy levels, which will be helpful in the interpretation of A-X single
      vibronic level emission spectra, if they can be observed. The electronic
      absorption spectra of the (2)Pi(32) spin component of the 0(0) (0) bands of all
      three radicals have been calculated assuming typical jet-expansion conditions and
      should be useful in future laser-induced fluorescence, resonance enhanced
      multiphoton ionization, or cavity ringdown searches for the electronic band
      systems.

PMID- 16626198
TI  - Electronic structures and spectroscopic properties of nitrido-osmium(VI)
      complexes with acetylide ligands [OsN(C[Triple Bond]CR)4]- R=H, CH3, and Ph by
      density functional theory calculation.
AB  - Electronic structures and spectroscopic properties of a series of nitrido-osmium
      (VI) complex ions with acetylide ligands, [OsN(C[Triple Bond]CR)(4)](-) (R[Double
      Bond]H, (1), CH(3) (2), and Ph (3)) were investigated theoretically. The
      structures of the complexes were fully optimized at the B3LYP and CIS level for
      the ground states and excited states, respectively. The calculated bond lengths
      of Os[Triple Bond]N (1.639 A in 1, 1.642 A in 2, and 1.643 A in 3) and Os-C
      (2.040 A in 1, 2.043 A in 2, and 2.042 A in 3) in ground state agree well with
      the experimental results. The bond length of Os[Triple Bond]N bond is lengthened
      by ca. 0.13 A in the A (3)B(2) excited state compared to the (1)A(1) ground
      state, which is consistent with the lower vibration frequency of nu(Os-N) (
      approximately 780 cm(-1)) in the excited state than that ( approximately 1175 cm(
      1)) in the ground state. Among the calculated dipole-allowed absorptions at
      lambda>250 nm, the intense absorption at 261 nm for 1, 266 nm for 2, and 300 nm
      for 3 were attributed to the (1)[pi(C[Triple Bond]C)]-->(1)[pi(*)(N[Triple
      Bond]Os)+pi(*)(C[Triple Bond]C)], (1)[pi(C[Triple Bond]C)]-->(1)[pi(*)(N[Triple
      Bond]Os)+pi(*)(C[Triple Bond]C)], and (1)[pi(C[Triple Bond]CPh)]-
      >(1)[pi(*)(N[Triple Bond]Os)+pi(*)(C[Triple Bond]CPh)], respectively. The lowest
      energy absorption at lambda(max)=393 nm for 1, 400 nm for 2, and 400 nm for 3
      were assigned as (1)[d(xy)(Os)+pi(C[Triple Bond]C)]-->(1)[pi(*)(N[Triple
      Bond]Os)+pi(*)(C[Triple Bond]C)], (1)[d(xy)(Os)+pi(C[Triple Bond]C)]-
      >(1)[pi(*)(N[Triple Bond]Os)+pi(*)(C[Triple Bond]C)], and
      (1)[d(xy)(Os)+pi(C[Triple Bond]CPh)]-->(1)[pi(*)(N[Triple Bond]Os)+pi(*)(C[Triple
      Bond]CPh)], respectively. The calculated phosphorescence emission at
      lambda(max)=581 nm for 1, 588 nm for 2, and 609 nm for 3 were originated from
      (3)[(pi(*)(N[Triple Bond]Os)+pi(*)(C[Triple Bond]C))(1)(d(xy)(Os)+pi(C[Triple
      Bond]C))(1)], (3)[(pi(*)(N[Triple Bond]Os)+pi(*)(C[Triple
      Bond]C))(1)(d(xy)(Os)+pi(C[Triple Bond]C))(1)], and (3)[(pi(*)(N[Triple
      Bond]Os)+pi(*)(C[Triple Bond]CPh))(1)(d(xy)(Os)+pi(C[Triple Bond]CPh))(1)]
      excited state, respectively.

PMID- 16626199
TI  - Optimal control of ultrafast laser driven many-electron dynamics in a polyatomic
      molecule: N-methyl-6-quinolone.
AB  - We report time-dependent configuration interaction singles calculations for the
      ultrafast laser driven many-electron dynamics in a polyatomic molecule, N-methyl
      6-quinolone. We employ optimal control theory to achieve a nearly state-selective
      excitation from the S(0) to the S(1) state, on a time scale of a few (
      approximately 6) femtoseconds. The optimal control scheme is shown to correct for
      effects opposing a state-selective transition, such as multiphoton transitions
      and other, nonlinear phenomena, which are induced by the ultrashort and intense
      laser fields. In contrast, simple two-level pi pulses are not effective in state
      selective excitations when very short pulses are used. Also, the dependence of
      multiphoton and nonlinear effects on the number of states included in the
      dynamical simulations is investigated.

PMID- 16626200
TI  - The state-to-state-to-state model for direct chemical reactions: application to
      D+H2-->HD+H.
AB  - A simple theoretical model is developed to predict the state-to-state dynamics of
      direct chemical reactions. Motivated by traditional ideas from transition state
      theory, expressions are derived for the reactive S matrix that may be computed
      using the local transition state dynamics. The key approximation involves the use
      of quantum bottleneck states to represent the near separable dynamics taking
      place near the transition state. Explicit expressions for the S matrix are
      obtained using a Franck-Condon treatment for the inelastic coupling between
      internal states of the collision complex. It is demonstrated that the energetic
      thresholds for various initial reagent states of the D+H(2) reaction can be
      understood in terms of our theory. Specifically, the helicity of the reagent
      states are found to correlate directly to the symmetry of the quantum bottleneck
      states, which thus possess very different thresholds. Furthermore, the rotational
      product state distributions for D+H(2) are found to be associated with
      interfering pathways through the quantum bottleneck states.

PMID- 16626201
TI  - Rovibrational characterization of X 2Sigma+ 11BH+ by the extrapolation of
      photoselected high Rydberg series in 11BH.
AB  - Optical-optical-optical triple-resonance spectroscopy of (11)BH isolates high
      Rydberg states that form series converging to rotational state specific
      ionization potentials in the vibrational levels of (11)BH(+) from nu(+)=0 through
      4. Limits defined by a comprehensive fit of these series to state-detailed
      thresholds yield rovibrational constants describing the X (2)Sigma(+) state of
      (11)BH(+). The data provide a first determination of the vibrational-rotational
      interaction parameter alpha(e)=0.4821 cm(-1) and a more accurate estimate of
      omega(e)=2526.58 cm(-1) together with the higher-order anharmonic terms
      omega(e)x(e)=61.98 cm(-1) and omega(e)y(e)=-1.989 cm(-1). The deperturbation and
      global fit of series to state-detailed limits also yield a precise value of the
      adiabatic ionization potential of (11)BH of 79 120.3+/-0.1 cm(-1), or 9.810 33+/
      1x10(-5) eV. High precision is afforded here by the use of graphical analysis
      techniques, narrow-bandwidth laser systems, and an analysis of newly observed,
      high principal quantum number Rydberg states that conform well with Hund's case
      (d) electron-core coupling limit.

PMID- 16626202
TI  - Photodissociation of propargyl bromide and photoionization of the propargyl
      radical.
AB  - Velocity map imaging was used to study the 193 nm photodissociation of propargyl
      bromide C(3)H(3)Br as well as the photoionization dynamics of the resulting
      propargyl radical C(3)H(3). Images were recorded by using single-photon vacuum
      ultraviolet ionization of the propargyl radical and by using two-photon resonant,
      three-photon ionization of the ground state Br((2)P(32)) and spin-orbit excited
      Br(*)((2)P(12)) atoms. Analysis of these data allowed the determination of the
      branching ratio Br:Br(*) as well as the photofragment angular distributions.
      Images of C(3)H(3) produced by the photodissociation of both C(3)H(3)Br and
      C(3)H(3)Cl were recorded at several energies between 8.97 and 9.12 eV, as well as
      at 9.86 eV, and showed no obvious internal energy dependence of the relative
      photoionization cross sections.

PMID- 16626203
TI  - The electronic structure of oxo-Mn(salen): single-reference and multireference
      approaches.
AB  - Using single- and multireference approaches we have examined many of the low
      lying electronic states of oxo-Mn(salen), several of which have not been explored
      previously. Large complete-active-space self-consistent-field (CASSCF)
      computations have been performed in pursuit of an accurate ordering for the
      lowest several electronic states. Basis set and relativistic effects have also
      been considered. For the geometry considered, our best results indicate the
      ground spin state to be a closed-shell singlet, followed by a pair of low-lying
      triplet states, with additional singlet states and the lowest quintet state lying
      significantly higher in energy. Hartree-Fock and density functional theory (DFT)
      results are obtained and are compared to the more robust CASSCF results. The
      Hartree-Fock results are qualitatively incorrect for the relative energies of the
      states considered. Popular density functionals such as BP86 and B3LYP are
      superior to Hartree-Fock for this problem, but they give inconsistent answers
      regarding the ordering of the lowest singlet and triplet states and they greatly
      underestimate the singlet-quintet gap. We obtained multiple Hartree-Fock and DFT
      solutions within a given spin multiplicity, and these solutions have been
      subjected to wave function stability analysis.

PMID- 16626204
TI  - Interatomic decay of inner-valence-excited states in clusters.
AB  - In an isolated atom, excitation of an inner valence electron above the outer
      valence subshell leads to creation of an autoionizing state. Recently, it has
      been demonstrated experimentally that in a cluster, the inner-valence-excited
      states can decay also by an interatomic mechanism which has been called resonant
      interatomic Coulombic decay (RICD). Here we show that RICD is indeed the leading
      but not the only possible interatomic decay mode of the inner-valence excitations
      in clusters. Using Ne (2s-->3p) excitation in MgNe cluster as an example, we
      explore the possible decay mechanisms and draw conclusions on their relative
      importance and on the nature of the corresponding decay products.

PMID- 16626205
TI  - Origin of threefold symmetric torsional potential of methyl group in 4
      methylstyrene.
AB  - To understand the effect of the para position vinyl group substitution in toluene
      on methyl torsion, we investigated 4-methylstyrene, a benchmark molecule with an
      extended pi conjugation. The assignment for a 33 cm(-1) band in the excitation
      spectrum to the 3a(2) torsional transition, in addition to the assignments
      suggested previously for the other bands in the excitation spectrum, leads to the
      model potentials for the ground as well as excited states with V(3) (")=19.6 cm(
      1), V(6) (")=-16.4 cm(-1) and V(3) (')=25.6 cm(-1), V(6) (')=-30.1 cm(-1),
      respectively. These potentials reveal that both in ground and excited states, the
      methyl group conformations are staggered with a 60 degrees phase shift between
      them. MP2 ab initio calculations support the ground state conformations
      determined from experiments, whereas Hartree-Fock calculations fail to do so. The
      origin of the modified ground state potential has been investigated by
      partitioning the barrier energy using the natural bond orbital (NBO) theoretical
      framework. The NBO analysis shows that the local delocalization (bond-antibond
      hyperconjugation) interactions of the methyl group with the parent molecule is
      sixfold symmetric. The threefold symmetric potential, on the other hand, stems
      from the interaction of the vinyl group and the adjacent ring pi bond. The
      threefold symmetric structural energy arising predominantly from the pi electron
      contribution is the barrier forming term that overwhelms the antibarrier
      contribution of the delocalization energy. The observed 60 degrees phase shift of
      the excited state potential is attributed to the pi(*)-sigma(*) hyperconjugation
      between out of plane hydrogens of the methyl group and the benzene ring.

PMID- 16626206
TI  - A three-dimensional ab initio potential energy surface and predicted infrared
      spectra for the He-N2O complex.
AB  - We report a three-dimensional ab initio potential energy surface for He-N(2)O
      using a supermolecular method at the coupled-cluster singles and doubles with
      noniterative inclusion of connected triple level. Besides the intermolecular
      stretching and bending modes, we included the Q(3) normal mode for the nu(3)
      antisymmetric stretching vibration of N(2)O molecule in order to simulate the
      observed infrared spectra in the nu(3) region of N(2)O, especially to explain the
      frequency shift of the band origin in the infrared spectra. The harmonic
      oscillator approximation is used for the potential curve of the Q(3) mode of the
      isolate N(2)O molecule. The intermolecular potential energy surfaces are
      calculated for five potential-optimized discrete variable representation grid
      points of the Q(3) mode. The three-dimensional discrete variable representation
      method was employed to calculate the rovibrational states without separating the
      inter- and intramolecular nuclear motions. The calculated transition frequencies
      and line intensities of the rotational transitions in the nu(3) region of N(2)O
      for the van der Waals ground vibrational state are in good agreement with the
      observed infrared spectra. The calculated band shifts are found to be 0.1704 and
      0.1551 cm(-1) for (4)He-N(2)O and (3)He-N(2)O, respectively, which agree well
      with the observed values of 0.2532 and 0.2170 cm(-1).

PMID- 16626207
TI  - The potential energy curve of the ground state of the potassium dimer,
      X1Sigma(g)+ K2.
AB  - The most recently published listings of vibrational term values and corresponding
      turning points of the potential energy curve of X (1)Sigma(g) (+) K(2) consist of
      two sets of data: energy levels v(")=0-73 and v(")=74-81. The two sets of data
      are found to exhibit a discontinuity. This is due to different Dunham
      coefficients used to produce a listing of turning points for levels v(")=0-73 and
      for levels v(")=74-81. This work provides an explicit, self-consistent listing of
      turning points for the entire domain of observed vibrational term values. New
      values are reported for levels v(")=53-81. This potential yields eigenvalues in
      excellent agreement with experimental vibrational term values and predicts two
      more bound levels. A "universal" function proposed in 1991 for predicting
      potential energy curves yields eigenvalues for levels v(")=0-81 (99.96% of
      dissociation) that have an average absolute deviation from the experiment of 0.95
      cm(-1).

PMID- 16626208
TI  - How to extend hard sphere density functional approximation to nonuniform nonhard
      sphere fluids: applicable to both subcritical and supercritical temperature
      regions.
AB  - A methodology for the formulation of density functional approximation (DFA) for
      nonuniform nonhard sphere fluids is proposed by following the spirit of a
      partitioned density functional approximation [Zhou, Phys. Rev. E 68, 061201
      (2003)] and mapping the hard core part onto an effective hard sphere whose high
      order part of the functional perturbation expansion is treated by existing hard
      sphere DFAs. The resultant density functional theory (DFT) formalism only needs a
      second order direct correlation function and pressure of the corresponding
      coexistence bulk fluid as inputs and therefore can be applicable to both
      supercritical and subcritical temperature cases. As an example, an adjustable
      parameter-free version of a recently proposed Lagrangian theorem-based DFA is
      imported into the present methodology; the resultant DFA is applied to Lennard
      Jones fluid under the influence of external fields due to a single hard wall, two
      hard walls separated by a small distance, a large hard sphere, and a spherical
      cavity with a hard wall. By comparing theoretical predictions with previous
      simulation data and those recently supplied for coexistence bulk fluid situated
      at "dangerous" regions, it was found that the present DFA can predict subtle
      structure change of the density profile and therefore is the most accurate among
      all existing DFT approaches. A detailed discussion is given as to why so
      excellent DFA for nonhard sphere fluids can be drawn forth from the present
      methodology and how the present methodology differs from previous ones. The
      methodology can be universal, i.e., it can be combined with any other hard sphere
      DFAs to construct DFA for other nonhard sphere fluids with a repulsive core.

PMID- 16626209
TI  - Ferroelectric ordering in imidazolium perchlorate.
AB  - Imidazolium perchlorate has been synthesized and studied over a wide range of
      temperatures by differential scanning calorimetry, x-ray diffraction, proton
      magnetic resonance, optical observation, and dielectric spectroscopy. Polymorphic
      solid-solid phase transitions have been disclosed at 487, 373, and 247 K. The
      crystal structure at 298 K has been determined as trigonal, space group R3m, Z=1
      with a=5.484(1) A and alpha=95.18(2) degrees. The imidazolium cations are
      strongly disordered, while the perchlorate ions are well ordered. At 385 K the
      crystal structure remains trigonal, space group R3m, a=5.554(1) A and
      alpha=95.30(2) degrees . Both ionic sublattices are orientationally disordered.
      Temperature evolution of the molecular dynamics of the imidazolium cation has
      been characterized. In spite of a high cationic disorder, dielectric measurements
      have revealed the polar properties of the crystal. It appears to be a new
      ferroelectric compound with the Curie point at 373 K. The spontaneous
      polarization originates predominantly from the behavior of slightly distorted
      perchlorate anion.

PMID- 16626210
TI  - Model for dynamics of inhomogeneous and bulk fluids.
AB  - An accurate model for the density of states (DOS) for strongly inhomogeneous and
      bulk fluids has been proposed based on gamma distributions. The contribution to
      the density of states from the collective dynamics is modeled as an incomplete
      gamma distribution and the high frequency region is obtained from the solution of
      the memory equation using a sech memory kernel. Using only the frequency moments
      as input, the model parameters for the collective dynamics are obtained by
      matching moments of the resulting distribution. The model results in an
      analytical expression for the self-diffusivity of the fluid. We present results
      for soft sphere fluids confined in slit-shaped pores as well as bulk soft sphere
      liquids. Comparisons of the DOS, velocity autocorrelation functions, and memory
      kernels with molecular dynamics simulations reveal that the model predicts
      features in the DOS over the entire frequency range and is able to capture
      changes in the DOS as a function of fluid density and temperature. As a result
      the predicted VACFs, memory kernels, and self-diffusivities are accurately
      predicted over a wide range of conditions. Since the frequency moments for bulk
      liquids can be obtained from pair correlation functions, our method provides a
      direct route from fluid structure to dynamics. For fluids confined in slit-shaped
      pores, where the frequency moments are obtained from molecular dynamics
      simulations, the predicted self-diffusivities capture the resulting oscillations
      due to variations in the solvation pressure, and in the case of smooth walled
      pores, the predictions are superior to those obtained using kinetic theory.

PMID- 16626211
TI  - Scaling law of shear viscosity in atomic liquid and liquid mixtures.
AB  - A scaling law relating the shear viscosity of one and two component liquid
      mixtures to their excess thermodynamic entropies defined through pair correlation
      functions is derived by approximating the mode coupling theory expressions of
      frictions and then combining with the Stokes-Einstein relation. Molecular
      dynamics simulation has been performed to generate the data of shear viscosity
      for one and two component liquid mixtures to test the derived scaling law. The
      derived scaling laws yield numerical results of shear viscosity for one component
      and two component liquid mixtures, which are in excellent agreement with the
      molecular dynamics simulation results for a wide range of density and interaction
      potential.

PMID- 16626212
TI  - Dynamic scaling of the critical binary mixture methanol-hexane.
AB  - Acoustical attenuation spectrometry, dynamic light scattering, shear viscosity,
      density, and heat capacity measurements of the methanol/n-hexane mixture of
      critical composition have been performed. The critical part in the sonic
      attenuation coefficients nicely fits to the empirical scaling function of the
      Bhattacharjee-Ferrell [Phys. Rev. A 24, 1643 (1981)] dynamic scaling model if the
      theoretically predicted scaled half-attenuation frequency Omega(12) (BF)=2.1 is
      used. The relaxation rates of order parameter fluctuations, as resulting from the
      acoustical spectra, within the limits of experimental error agree with those from
      a combined evaluation of the light scattering and shear viscosity measurements.
      Both series of data display power law with amplitude Gamma(0)=44x10(9) s(-1). The
      amplitude of the fluctuation correlation length follows as xi(0)=0.33 nm from the
      light scattering data and as xi(0)=0.32 nm from the amplitude of the singular
      part of the heat capacity if the two-scale factor universality relation is used.
      The adiabatic coupling constant g=0.11 results from the amplitude of the critical
      contribution to the acoustical spectrum near the critical point, in conformity
      with g=0.12 as following from the variation of the critical temperature with
      pressure along the critical line and the thermal expansion coefficient.

PMID- 16626213
TI  - The melting point of ice Ih for common water models calculated from direct
      coexistence of the solid-liquid interface.
AB  - In this work we present an implementation for the calculation of the melting
      point of ice I(h) from direct coexistence of the solid-liquid interface. We use
      molecular dynamics simulations of boxes containing liquid water and ice in
      contact. The implementation is based on the analysis of the evolution of the
      total energy along NpT simulations at different temperatures. We report the
      calculation of the melting point of ice I(h) at 1 bar for seven water models:
      SPC/E, TIP4P, TIP4P-Ew, TIP4P/ice, TIP4P/2005, TIP5P, and TIP5P-E. The results
      for the melting temperature from the direct coexistence simulations of this work
      are in agreement (within the statistical uncertainty) with those obtained
      previously by us from free energy calculations. By taking into account the
      results of this work and those of our free energy calculations, recommended
      values of the melting point of ice I(h) at 1 bar for the above mentioned water
      models are provided.

PMID- 16626214
TI  - Cation electric field is related to hydration energy.
AB  - Electronic structure calculations on ions that use dielectric continuum theory to
      mimic solvent around the bare ionic solutes are often prone to make large errors
      in the hydration energies. It is found for cations that much of the error can be
      accounted for by a simple linear correlation with the maximum value found
      anywhere on the dielectric cavity surface of the solute potential or, even
      better, the outgoing normal electric field, thus mirroring analogous results
      previously obtained for anions. This correlation allows for significantly
      improved estimates of cation hydration energies while still retaining cavities of
      physically reasonable size in determination of the bulk dielectric contributions.

PMID- 16626215
TI  - Accurate measurement of 13C-15N distances with solid-state NMR.
AB  - Solid-state NMR technique for measuring distances between heteronuclei in static
      powder samples is described. It is based on a two-dimensional single-echo scheme
      enhanced with adiabatic cross polarization. As an example, the results for
      intramolecular distances in alpha-crystalline form of glycine are presented. The
      measured NMR distances (13)C(alpha)-(15)N and (13)C(')-(15)N are 1.496+/-0.002
      and 2.50+/-0.02 A, respectively.

PMID- 16626216
TI  - Aggregation of [70]fullerene in presence of acetonitrile: a chemical kinetic
      experiment.
AB  - [70]fullerene solutions in carbon tetrachloride and o-xylene exhibit a noteworthy
      spectral variation with time when acetonitrile is added. This has been ascribed
      to self-aggregation of [70]fullerene caused by the repulsion between polar
      acetonitrile and hydrophobic [70]fullerene, and the aggregation numbers have been
      determined from a kinetic scheme and also from a scanning electron microscopic
      study. The numbers thus obtained follow a cuboctahedral stacking pattern proposed
      recently and also agree with the magic formula n=55+3m (m=1 to 14) proposed by
      Branz et al. for [60]fullerene clusters [Phys. Rev. B. 66, 094107 (2002)].

PMID- 16626217
TI  - Solvent reorganization of electron transitions in viscous solvents.
AB  - We develop a model of electron transfer reactions at conditions of nonergodicity
      when the time of solvent relaxation crosses the observation time window set up by
      the reaction rate. Solvent reorganization energy of intramolecular electron
      transfer in a charge-transfer molecule dissolved in water and acetonitrile is
      studied by molecular dynamics simulations at varying temperatures. We observe a
      sharp decrease of the reorganization energy at a temperature identified as the
      temperature of structural arrest due to cage effect, as discussed by the mode
      coupling theory. This temperature also marks the onset of the enhancement of
      translational diffusion relative to rotational relaxation signaling the breakdown
      of the Stokes-Einstein relation. The change in the reorganization energy at the
      transition temperature reflects the dynamical arrest of the slow, collective
      relaxation of the solvent related to the relaxation of the solvent dipolar
      polarization. An analytical theory proposed to describe this effect agrees well
      with both the simulations and experimental Stokes shift data. The theory is
      applied to the analysis of charge-transfer kinetics in a low-temperature glass
      former. We show that the reorganization energy is substantially lower than its
      equilibrium value for the low-temperature portion of the data. The theory
      predicts the possibility of discontinuous changes in the dependence of the
      electron transfer rate on the free energy gap when the reaction switches between
      ergodic and nonergodic regimes.

PMID- 16626218
TI  - Pressure dependence of local structure in liquid carbon disulfide.
AB  - High pressure x-ray diffraction measurements on liquid carbon disulfide up to 1.2
      GPa are performed by using an energy dispersion method. The results are compared
      with a molecular dynamics calculation with usual Lennard-Jones potential. They
      give very good agreement for all pressures measured. It becomes clear that the
      liquid structure changes like hard core liquid up to the pressure just below
      crystallizing point. The relation between structural change and optical response
      at high pressure is discussed.

PMID- 16626219
TI  - Dielectric properties of glycerol/water mixtures at temperatures between 10 and
      50 degrees C.
AB  - At six temperatures T between 10 and 50 degrees C and at mole fractions x(g) of
      glycerol (0<x(g)<or=0.9) the complex (electric) permittivity epsilon(nu) of
      glycerol/water mixtures has been measured as a function of frequency nu between 1
      MHz and 40 GHz. The spectra of the glycerol/water mixtures can be well
      represented by a Davidson-Cole [J. Chem. Phys. 18, 1417 (1950)] relaxation
      function that reveals an unsymmetric relaxation time distribution. The effective
      dipole orientation correlation factor derived from the static permittivity
      displays an unspectacular behavior upon mixture composition. The dielectric
      relaxation time reveals a simple relation to the shear viscosity of the mixtures,
      but both quantities are not proportional to one another. The relaxation times at
      high temperatures nicely complement previously determined low temperature data,
      following a Vogel-Fulcher-Tammann-Hesse [Z. Phys. 22, 645 (1925); J. Am. Chem.
      Ceram. Soc. 8, 339 (1923); Z. Anorg. Allg. Chem. 156, 245 (1926)] (VFTH)
      temperature dependence. When the Eyring behavior is assumed a limiting high
      temperature form of the VFTH relation, enthalpy, and entropy of activation values
      are found which adopt significantly higher values in the glycerol rich mixtures
      than in the water rich liquids. The relaxation time distribution parameter at
      high water content indicates a dynamically heterogeneous structure of the
      liquids. Likely there exist glycerol rich and water rich microphases.

PMID- 16626220
TI  - Time evolution of a single spin inhomogeneously coupled to an interacting spin
      environment.
AB  - We study the time evolution of a single spin coupled by exchange interaction to
      an environment of interacting spin bath modeled by the XY Hamiltonian. By
      evaluating the spin correlator of the single spin, we observed that the decay
      rate of the spin oscillations strongly depends on the relative magnitude of the
      exchange coupling between the single spin and its nearest neighbor J(') and
      coupling among the spins in the environment J. The decoherence time varies
      significantly based on the relative coupling magnitudes of J and J('). The decay
      rate law has a Gaussian profile when the two exchange couplings are of the same
      order J(') approximately J but converts to exponential and then a power law as we
      move to the regimes of J(')>J and J(')<J. We also show that the spin oscillations
      propagate from the single spin to the environmental spins with a certain speed.
      The effect of varying the anisotropic parameter, external magnetic field, and
      temperature on the decaying rate of the spin state is also discussed.

PMID- 16626221
TI  - Molecular reorientation in hydrogen-bonding liquids: through algebraic
      approximately t-32 relaxation toward exponential decay.
AB  - We present a model for the description of orientational relaxation in hydrogen
      bonding liquids. The model contains two relaxation parameters which regulate the
      intensity and efficiency of dissipation, as well as the memory function which is
      responsible for the short-time relaxation effects. It is shown that the
      librational portion of the orientational relaxation is described by an algebraic
      approximately t(-32) contribution, on top of which more rapid and nonmonotonous
      decays caused by the memory effects are superimposed. The long-time behavior of
      the orientational relaxation is exponential, although nondiffusional. It is
      governed by the rotational energy relaxation. We apply the model to interpret
      recent molecular dynamic simulations and polarization pump-probe experiments on
      HOD in liquid D(2)O [C. J. Fecko et al., J. Chem. Phys. 122, 054506 (2005)].

PMID- 16626222
TI  - Negative linear compressibility in confined dilatating systems.
AB  - The role of a matrix response to a fluid insertion is analyzed in terms of a
      perturbation theory and Monte Carlo simulations applied to a hard sphere fluid in
      a slit of fluctuating density-dependent width. It is demonstrated that a coupling
      of the fluid-slit repulsion, spatial confinement, and the matrix dilatation acts
      as an effective fluid-fluid attraction, inducing a pseudocritical state with
      divergent linear compressibility and noncritical density fluctuations. An
      appropriate combination of the dilatation rate, fluid density, and the slit size
      leads to the fluid states with negative linear compressibility. It is shown that
      the switching from positive to negative compressibility is accompanied by an
      abrupt change in the packing mechanism.

PMID- 16626223
TI  - An apparent critical point in binary mixtures: experimental and simulation study.
AB  - We report the experimental and simulation studies for the system of nitrobenzene
      cyclododecane, showing an apparent critical point, which lies in their
      metastable, experimentally inaccessible state, below their melting point,
      affecting physical and chemical properties of this system in the stable liquid
      phase. The nonlinear dielectric effect (NDE) was measured in the mixture of
      nitrobenzene with cyclododecane. The mixture has been found to show an apparent
      critical point which lies below the melting point, manifested as anomalous NDE
      behavior in the vicinity of the critical concentrations in the stable liquid
      phase. The melting temperature of this system was estimated using the
      differential scanning calorimetry method. For such a system, we also performed
      Monte Carlo (MC) simulations that aimed to analyze the kinds of phase transitions
      observed and the conditions of their occurrence in Lennard-Jones mixture. The
      enthalpy, configurational energy, and radial distribution function have been
      estimated by the MC simulation method in the N-P-T system. Immiscibility
      conditions according to the approach by Schoen and Hoheisel [Mol. Phys. 57, 65
      (1986)] are also discussed.

PMID- 16626224
TI  - Critical behavior of 2,6-dimethylpyridine-water: measurements of specific heat,
      dynamic light scattering, and shear viscosity.
AB  - The specific heat C(p) at constant pressure, the shear viscosity eta(s), and the
      mutual diffusion coefficient D of the 2,6-dimethylpyridine-water mixture of
      critical composition have been measured in the homogeneous phase at various
      temperatures near the lower critical demixing temperature T(c). The amplitude of
      the fluctuation correlation length xi(0)=(0.198+/-0.004) nm has been derived from
      a combined evaluation of the eta(s) and D data. This value is in reasonable
      agreement with the one obtained from the amplitude A(+)=(0.26+/-0.01) J(g K) of
      the critical term in the specific heat, using the two-scale-factor universality
      relation. Within the limits of error the relaxation rate Gamma of order parameter
      fluctuations follows power law with the theoretical universal exponent and with
      the amplitude Gamma=(25+/-1)x10(9) s(-1). No indications of interferences of the
      critical fluctuations with other elementary chemical reactions have been found. A
      noteworthy result is the agreement of the background viscosity eta(b), resulting
      from the treatment of eta(s) and D data, with the viscosity eta(s)(nu=0)
      extrapolated from high-frequency viscosity data. The latter have been measured in
      the frequency range of 5-130 MHz using a novel shear impedance spectrometer.

PMID- 16626225
TI  - Optical control of the coherent acoustic vibration of metal nanoparticles.
AB  - Optical control of the coherent breathing vibrations of silver nanospheres is
      demonstrated using a high-sensitivity femtosecond pump-probe technique in a
      double-pump pulse configuration. Oscillation of the fundamental mode that usually
      dominates the time-domain vibrational response can thus be stopped, permitting
      observation of the first order radial mode and determination of its properties.
      These are found to be in agreement with the predictions of the model of an
      elastic sphere embedded in an elastic matrix.

PMID- 16626226
TI  - Competing interactions in two dimensional Coulomb systems: surface charge
      heterogeneities in coassembled cationic-anionic incompatible mixtures.
AB  - A binary mixture of oppositely charged components confined to a plane such as
      cationic and anionic lipid bilayers may exhibit local segregation. The relative
      strengths of the net short range interactions, which favors macroscopic
      segregation, and the long range electrostatic interactions, which favors mixing,
      determine the length scale of the finite size or microphase segregation. The free
      energy of the system can be examined analytically in two separate regimes, when
      considering small density fluctuations at high temperatures and when considering
      the periodic ordering of the system at low temperatures [F. J. Solis, S. I.
      Stupp, and M. Olvera de la Cruz, J. Chem. Phys. 122, 054905 (2005)]. A simple
      molecular dynamics simulation of oppositely charged monomers, interacting with a
      short range Lennard-Jones potential and confined to a two dimensional plane, is
      examined at different strengths of short and long range interactions. The system
      exhibits well-defined domains that can be characterized by their periodic length
      scale as well as the orientational ordering of their interfaces. By adding salt,
      the ordering of the domains disappears and the mixture macroscopically phase
      segregates in agreement with analytical predictions.

PMID- 16626227
TI  - CO adsorption and CO and O coadsorption on Rh(111) studied by reflection
      absorption infrared spectroscopy and density functional theory.
AB  - The adsorption of carbon monoxide on Rh(111) and on oxygen modified Rh(111) was
      investigated using thermal desorption spectroscopy, reflection absorption
      infrared spectroscopy (RAIRS), and density functional theory. The results show
      that CO adsorbs on Rh(111) in on top sites at low coverages. With increasing
      coverage hollow sites and bridge sites get occupied according to the RAIRS
      results. A new vibrational feature at high wave numbers was found in the on top
      region of the CO stretching frequency. This feature can be explained by a local
      high density CO structure where two CO molecules are adsorbed in the ( radical3x
      radical3)R30 degrees structure. The coadsorption of oxygen and carbon monoxide
      leads to a shift of the CO stretching frequency to higher wave numbers with
      increasing O to CO ratio. CO adsorption on a (2x1) oxygen layer is possible and
      RAIRS shows that the CO adsorbs in on top and most likely in bridge sites in this
      case.

PMID- 16626228
TI  - Quantifying electron transfer during hyperthermal scattering of C60+ from Au(111)
      and n-alkylthiol self-assembled monolayers.
AB  - A tandem time-of-flight mass spectrometer with an intermediate surface was used
      to quantify electron transfer during glancing incidence scattering of
      hyperthermal C(60) (+) (E(coll)=250-500 eV, theta(in)=75 degrees ) from (i) self
      assembled monolayers of n-alkylthiols on gold (of various chain lengths), (ii)
      partly fluorinated alkylthiols on gold, as well as (iii) clean gold surfaces.
      Self-assembled monolayers (SAMs) behave as insulating layers with their
      thicknesses determining the electron tunneling probability during collision.
      Correspondingly, a roughly exponential dependence of the neutralization
      probability on the chain length n was found. A pronounced dependence of the
      neutral yield on the primary beam kinetic energy indicates that dynamic SAM
      deformation and associated projectile penetration depth also play a role in
      determining electron transfer efficiency. Results are consistent with the
      molecular deformability of SAMs as determined with other experimental methods.

PMID- 16626229
TI  - Some estimates of the surface tension of curved surfaces using density functional
      theory.
AB  - Density functional theory is used to calculate the surface tension of planar and
      slightly curved surfaces, which can be written as gamma(R)=gamma(infinity)(1
      2delta(infinity)R), where R is the radius of curvature of the surface.
      Calculations are performed for a Lennard-Jones fluid, split into a hard-sphere
      repulsive potential and an attractive part. The repulsive part is treated using
      the local density approximation. The attractive part is treated using a high
      temperature approximation (HTA) in which the pair correlation function is
      approximated by the Percus-Yevick pair correlation function of a uniform hard
      sphere fluid evaluated at a position-dependent average density. An expression
      relating the Tolman length delta(infinity) to the density profile of the planar
      surface is derived. Numerical results are presented for the planar surface
      tension gamma(infinity) and for delta(infinity) and are compared with those using
      mean field theory (MFT) and with those using the square-gradient approximation.
      Values for gamma(infinity) using the HTA are 30%-40% higher than those using MFT.
      Values for delta(infinity) using the HTA are around -0.1 (in units of the Lennard
      Jones parameter sigma) and only weakly dependent on temperature. These values are
      less negative than the values from MFT. The square-gradient approximation gives
      reasonable estimates of the more accurate nonlocal results for both the MFT and
      the HTA.

PMID- 16626230
TI  - Mesoscopic nonequilibrium thermodynamics of solid surfaces and interfaces with
      triple junction singularities under the capillary and electromigration forces in
      anisotropic three-dimensional space.
AB  - A theory of irreversible thermodynamics of curved surfaces and interfaces with
      triple junction singularities is elaborated to give a full consideration of the
      effects of the specific surface Gibbs free energy anisotropy in addition to the
      diffusional anisotropy, on the morphological evolution of surfaces and interfaces
      in crystalline solids. To entangle this intricate problem, the internal entropy
      production associated with arbitrary virtual displacements of triple junction and
      ordinary points on the interfacial layers, embedded in a multicomponent,
      multiphase, anisotropic composite continuum system, is formulated by adapting a
      mesoscopic description of the orientation dependence of the chemical potentials
      in terms of the rotational degree of freedom of individual microelements. The
      rate of local internal entropy production resulted generalized forces and
      conjugated fluxes not only for the grain boundary triple junction transversal and
      longitudinal movements, but also for the ordinary points. The natural combination
      of the mesoscopic approach coupled with the rigorous theory of irreversible
      thermodynamics developed previously by the global entropy production hypothesis
      yields a well-posed, nonlinear, moving free-boundary value problem in two
      dimensional (2D) space, as a unified theory. The results obtained for 2D space
      are generalized into the three-dimensional continuum by utilizing the invariant
      properties of the vector operators in connection with the descriptions of curved
      surfaces in differential geometry. This mathematical model after normalization
      and scaling procedures may be easily adapted for computer simulation studies
      without introducing any additional phenomenological system parameters (the
      generalized mobilities), other than the enlarged concept of the surface
      stiffness.

PMID- 16626231
TI  - Coherent control approaches to light guidance in the nanoscale.
AB  - Concepts of coherent control are extended to manipulate light in subdiffraction
      length scales via nanoparticle arrays. Phase and polarization control are first
      introduced and applied to control the pathway of electromagnetic energy through
      multiple branching nanoarray intersections, leading to an ultrafast optical
      nanoswitch below the diffraction limit. The genetic algorithm is next generalized
      to provide a systematic design tool, wherein both the properties of the
      excitation field and the structural parameters of the material system are
      optimized so as to make nanodevices with desired functionality. The scheme is
      used to gain insight into the interplay between the interactions that underlies
      the coherent propagation of electromagnetic energy via nanoparticle arrays.
      Implications to several research fields, including single molecule spectroscopy,
      spatially confined chemistry, optical logic, and nanoscale sensing, are
      envisioned.

PMID- 16626232
TI  - Flow structure of water in carbon nanotubes: poiseuille type or plug-like?
AB  - We have conducted molecular dynamics simulations of water flow in carbon
      nanotubes (CNTs) for (6,6) to (20,20) CNTs at a streaming velocity of 100 ms. The
      fluidized piston model (FPM) and the ice piston model (IPM) are employed to drive
      flow through the CNTs. The results show that the single-file water flow inside
      (6,6) CNT has a convex upward streaming velocity profile, whereas the velocity
      profiles in (10,10) to (20,20) CNTs are flat except near the tube wall. The flow
      structure of cylindrical water in the (8,8) CNT is intermediate between that for
      the (6,6) CNT and the larger CNTs. The flow parameters are found not to exhibit
      any dependence on streaming velocity at up to 300 ms in the (12,12) CNT. The
      hydrogen bond lifetimes of water flowing in CNTs tend to be longer than for the
      corresponding equilibrium states, and nonzero flow does not reduce the
      microscopic structure or structural robustness (hydrogen bond lifetime). Although
      the atomic density profile varies with tube diameter, reflecting the change in
      static microscopic structure of flow from single file to cylindrical, tube
      diameter does not induce a clear transition in streaming velocity, temperature,
      or hydrogen bond lifetime over this diameter range. The results suggest that
      water flow in CNTs of this size is more pluglike than Poiseuille type, although
      the flow structure does not strictly accord with either definition.

PMID- 16626233
TI  - Prediction of phase behavior of nanoconfined Lennard-Jones fluids with density
      functional theory based on the first-order mean spherical approximation.
AB  - The recently proposed first-order mean spherical approximation (FMSA) [Y. Tang,
      J. Chem. Phys. 121, 10605 (2004)] for inhomogeneous fluids is extended to study
      the phase behavior of nanoconfined Lennard-Jones fluids, which is consistent with
      the phase equilibria calculation of the corresponding bulk fluid. With a
      combination of fundamental measure theory, FMSA provides Helmholtz free energy
      and direct correlation function to formulate density functional theory, which
      implementation is as easy as the mean-field theory. Following previous success in
      predicting density profiles inside slit pores, this work is focused specially on
      the vapor-liquid equilibrium of the Lennard-Jones fluids inside these pores. It
      is found that outside the critical region FMSA predicts well the equilibrium
      diagram of slit pores with the sizes of 5.0, 7.5, and 10 molecular diameters by
      comparing with available computer simulation data. As a quantitative method, FMSA
      can be treated as an extension from its bulk calculation, while the mean-field
      theory is only qualitative, as its bulk version.

PMID- 16626234
TI  - Complex Ohmic conductance of electrolytes in rectangular microchannels.
AB  - Motivated by the interest that microelectrolytic systems are gaining in the
      development of the so-called lab-on-a-chip systems, i.e., miniature microfluidic
      devices for biochemical analysis, we present an analytical study of Ohmic
      conduction in rectangular charged microchannels filled with electrolytic
      solution. The study complements a previous one [M. Campisi et al., J. Chem. Phys.
      123, 204724 (2005)], concerning ac electro-osmosis. The problem is framed within
      the theory of nonequilibrium thermodynamics and is based on the solution of the
      incompressible Navier-Stokes equation with an electrical body force due to the
      interaction of the applied electric field with the charged electric double layer
      (EDL) which forms at the solid-liquid interface. We analyze in detail the
      dependence of the system complex conductance on the ratio linear dimensions over
      Debye length with an eye on finite EDL effects, and compare its scaling
      properties with those of electrokinetic and hydraulic complex conductances.

PMID- 16626235
TI  - Spatial distributions of desorbing products in steady-state NO and N2O reductions
      on Pd(110).
AB  - The angular and velocity distributions of desorbing product N(2) were examined
      over the crystal azimuth in steady-state NO+CO and N(2)O+CO reactions on Pd(110)
      by cross-correlation time-of-flight techniques. At surface temperatures below 600
      K, N(2) desorption in both reactions splits into two directional lobes collimated
      along 41 degrees -45 degrees from the surface normal toward the [001] and [001]
      directions. Above 600 K, the normally directed N(2) desorption is enhanced in the
      NO reduction. Each product desorption component, as well as CO(2), shows a fairly
      asymmetric distribution about its collimation axis. Two factors, i.e., the
      anisotropic site structures and the reactant orientation and movements, are
      operative to induce such asymmetry, depending on the product emission mechanism.

PMID- 16626236
TI  - Spin distribution and hydrogen-bond effect in ferromagnetic alpha-phase crystal
      of 2-(2',5'-dihydroxyphenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxy
      3-oxide.
AB  - The ferromagnetic phenyl nitronyl nitroxide derivate alpha-phase 2-(2('),5(')
      dihydroxyphenyl)- 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxy-3-oxide has
      been studied by the electronic structure calculation based on the density
      functional theory. The result shows that the spin delocalization due to
      hyperconjugation effect plays an important role in the spin distribution and
      ferromagnetic coupling of the crystal.

PMID- 16626237
TI  - Sliding friction between polymer surfaces: a molecular interpretation.
AB  - For two contacting rigid bodies, the friction force F is proportional to the
      normal load and independent of the macroscopic contact area and relative velocity
      V (Amonton's law). With two mutually sliding polymer samples, the surface
      irregularities transmit deformation to the underlying material. Energy loss along
      the deformation cycles is responsible for the friction force, which now appears
      to depend strongly on V [see, e.g., N. Maeda et al., Science 297, 379 (2002)]. We
      base our theoretical interpretation on the assumption that polymer chains are
      mainly subjected to oscillatory "reptation" along their "tubes." At high
      deformation frequencies-i.e., with a large sliding velocity V-the internal
      viscosity due to the rotational energy barriers around chain bonds hinders
      intramolecular mobility. As a result, energy dissipation and the correlated
      friction force strongly diminish at large V. Derived from a linear differential
      equation for chain dynamics, our results are basically consistent with the
      experimental data by Maeda et al. [Science 297, 379 (2002)] on modified
      polystyrene. Although the bulk polymer is below T(g), we regard the first few
      chain layers below the surface to be in the liquid state. In particular, the
      observed maximum of F vs V is consistent with physically reasonable values of the
      molecular parameters. As a general result, the ratio FV is a steadily decreasing
      function of V, tending to V(-2) for large velocities. We evaluate a much smaller
      friction for a cross-linked polymer under the assumption that the junctions are
      effectively immobile, also in agreement with the experimental results of Maeda et
      al. [Science 297, 379 (2002)].

PMID- 16626238
TI  - Dielectric response of a polar fluid trapped in a spherical nanocavity.
AB  - We present extensive molecular dynamics simulation results for the structure and
      the static and dynamical responses of a droplet of 1000 soft spheres carrying
      extended dipoles and confined to spherical cavities of radii R=2.5, 3, and 4 nm
      embedded in a dielectric continuum of permittivity epsilon(')>or=1. The
      polarization of the external medium by the charge distribution inside the cavity
      is accounted for by appropriate image charges. We focus on the influence of the
      external permittivity epsilon(') on the static and dynamic properties of the
      confined fluid. The density profile and local orientational order parameter of
      the dipoles turn out to be remarkably insensitive to epsilon('). Permittivity
      profiles epsilon(r) inside the spherical cavity are calculated from a generalized
      Kirkwood formula. These profiles oscillate in phase with the density profiles and
      go to a "bulk" value epsilon(b) away from the confining surface; epsilon(b) is
      only weakly dependent on epsilon('), except for epsilon(')=1 (vacuum), and is
      strongly reduced compared to the permittivity of a uniform (bulk) fluid under
      comparable thermodynamic conditions. The dynamic relaxation of the total dipole
      moment of the sample is found to be strongly dependent on epsilon(') and to
      exhibit oscillatory behavior when epsilon(')=1; the relaxation is an order of
      magnitude faster than in the bulk. The complex frequency-dependent permittivity
      epsilon(omega) is sensitive to epsilon(') at low frequencies, and the zero
      frequency limit epsilon(omega=0) is systematically lower than the bulk value
      epsilon(b) of the static permittivity.

PMID- 16626239
TI  - Molecular dynamics simulation of the nematic liquid crystal phase in the presence
      of an intense magnetic field.
AB  - The influence of an intense external field on the dynamics of the nematic liquid
      crystal phase is investigated using a molecular dynamics simulation for the Gay
      Berne nematogen under isobaric-isothermal conditions. The molecular dynamics as a
      function of the second-rank orientational order parameter P<2> for a system
      consisting of a nematic liquid crystal in the presence of an intense magnetic
      field is compared with that of a similar system without the field. The
      translational motion of molecules is determined as a function of the
      translational diffusion coefficient tensor and the anisotropy and compared with
      the values predicted theoretically. The rotational dynamics of molecules is
      analyzed using the first- and the second-rank orientational time correlation
      functions. The translational diffusion coefficient parallel with respect to the
      director is constrained by the intense field, although the perpendicular one is
      decreased as the P<2> is increased, just as it is in the system without the
      field. However, no essential effect of the strong magnetic field is observed in
      the rotational molecular dynamics. Further, the rotational diffusion coefficient
      parallel with respect to the director obtained from the first-rank orientational
      time correlation function in the simulation is qualitatively in agreement with
      that in the real nematic liquid crystalline molecules. The P<2> dependence of the
      rotational diffusion coefficient for the system with the intense magnetic field
      shows a tendency similar to that for the system without the field.

PMID- 16626240
TI  - Effects of confinement on the order-disorder transition of diblock copolymer
      melts.
AB  - The effects of confinement on the order-disorder transition of diblock copolymer
      melts are studied theoretically. Confinements are realized by restricting diblock
      copolymers in finite spaces with different geometries (slabs, cylinders, and
      spheres). Within the random phase approximation, the correlation functions are
      calculated using the eigenvalues and eigenfunctions of the Laplacian operator
      inverted Delta(2) in the appropriate geometries. This leads to a size-dependent
      scattering function, and the minimum of the inverse scattering function
      determines the spinodal point of the homogeneous phase. For diblock copolymers
      confined in a slab or in a cylindrical nanopore, the spinodal point of the
      homogeneous phase (chiN)(s) is found to be independent of the confinement. On the
      other hand, for diblock copolymers confined in a spherical nanopore, (chiN)(s)
      depends on the confinement and it oscillates as a function of the radius of the
      sphere. Further understanding of the finite-size effects is provided by examining
      the fluctuation modes using the Landau-Brazovskii model.

PMID- 16626241
TI  - Modeling electrode polarization in dielectric spectroscopy: Ion mobility and
      mobile ion concentration of single-ion polymer electrolytes.
AB  - A novel method is presented whereby the parameters quantifying the conductivity
      of an ionomer can be extracted from the phenomenon of electrode polarization in
      the dielectric loss and tan delta planes. Mobile ion concentrations and ion
      mobilities were determined for a poly(ethylene oxide)-based sulfonated ionomer
      with Li(+), Na(+), and Cs(+) cations. The validity of the model was confirmed by
      examining the effects of sample thickness and temperature. The Vogel-Fulcher
      Tammann (VFT)-type temperature dependence of conductivity was found to arise from
      the Arrhenius dependence of ion concentration and VFT behavior of mobility. The
      ion concentration activation energy was found to be 25.2, 23.4, and 22.3+/-0.5
      kJmol for ionomers containing Li(+), Na(+), and Cs(+), respectively. The
      theoretical binding energies were also calculated and found to be approximately 5
      kJmol larger than the experimental activation energies, due to stabilization by
      coordination with polyethylene glycol segments. Surprisingly, the fraction of
      mobile ions was found to be very small, <0.004% of the cations in the Li(+)
      ionomer at 20 degrees C.

PMID- 16626242
TI  - Dynamic interactions between nematic point defects in the spinning extrusion duct
      of spiders.
AB  - Spider silk fibers have remarkable mechanical properties as a result of an
      ultraoptimized spinning process. Silk fibers are spun from a lyotropic nematic
      liquid crystalline anisotropic fluid phase which undergoes significant structural
      changes throughout the spinning pathway. In the silk extrusion duct, those
      structural changes are expected to be driven by elastic-mediated interactions
      between point defects. In this work, the interaction between two point defects of
      opposite topological charges located on the axis of a cylindrical cavity is
      studied using a tensor order parameter formalism. Distinct regimes leading to
      defect annihilation and structural transitions are described in detail. The
      driving force setting the defects into motion is also examined. The different
      results suggest that the tensorial approach is primordial in describing the
      complicated physics of the problem. The phenomenon described is important to the
      understanding of the process-induced structuring of silk fibers and to defect
      physics in a more general context.

PMID- 16626243
TI  - Photon echo spectroscopy of porphyrins and heme proteins: effects of
      quasidegenerate electronic structure on the peak shift decay.
AB  - Three pulse photon echo peak shift spectroscopy and transient grating
      measurements on Zn-substituted cytochrome c, Zn-tetraphenylporphyrin, and Zn
      protoporphyrin IX are reported. The effects of protein conformation, axial
      ligation, and solvent are investigated. Numerical simulations of the peak shift
      and transient grating experiments are presented. The simulations employed
      recently derived optical response functions for square-symmetric molecules with
      doubly degenerate excited states. Simulations exploring the effects of excited
      state energy splitting, symmetric and asymmetric fluctuations, and excited-state
      lifetime show that the time scales of the peak shift decay in the three-level
      system largely reflect the same dynamics as in the two-level system. However, the
      asymptotic peak shift, which is a clear indicator of inhomogeneous broadening in
      a two-level system, must be interpreted more carefully for three-level systems,
      as it is also influenced by the magnitude of the excited-state splitting. The
      calculated signals qualitatively reproduce the data.

PMID- 16626244
TI  - Lattice model of equilibrium polymerization. V. Scattering properties and the
      width of the critical regime for phase separation.
AB  - Dynamic clustering associated with self-assembly in many complex fluids can
      qualitatively alter the shape of phase boundaries and produce large changes in
      the scale of critical fluctuations that are difficult to comprehend within the
      existing framework of theories of critical phenomena for nonassociating fluids.
      In order to elucidate the scattering and critical properties of associating
      fluids, we consider several models of equilibrium polymerization that describe
      widely occurring types of associating fluids at equilibrium and that exhibit the
      well defined cluster geometry of linear polymer chains. Specifically, a Flory
      Huggins-type lattice theory is used, in conjunction with the random phase
      approximation, to compute the correlation length amplitude xi(o) and the Ginzburg
      number Gi corresponding, respectively, to the scale of composition fluctuations
      and to a parameter characterizing the temperature range over which Ising critical
      behavior is exhibited. Our calculations indicate that upon increasing the
      interparticle association energy, the polymer chains become increasingly long in
      the vicinity of the critical point, leading naturally to a more asymmetric phase
      boundary. This increase in the average degree of polymerization implies, in turn,
      a larger xi(o) and a drastically reduced width of the critical region (as
      measured by Gi). We thus obtain insight into the common appearance of asymmetric
      phase boundaries in a wide range of "complex" fluids and into the observation of
      apparent mean field critical behavior even rather close to the critical point.

PMID- 16626245
TI  - Pretransitional behavior in the isotropic phase of a nematic liquid crystal with
      the transverse permanent dipole moment.
AB  - The results presented give the evidence for the quasicritical, pretransitional
      behavior of dielectric properties in the isotropic phase of a rodlike nematic
      liquid crystal with the transverse permanent dipole moment. Studies were
      conducted in 2-cyano-4-pentylbiphenyl 4-(trans-4-pentylcyclohexyl) benzoate,
      focusing on the static-and ionic-dominated low-frequency (LF) regions. For the
      static dielectric permittivity [epsilon(')(T)] the application of the derivative
      analysis revealed the pretransitional anomaly associated with the specific heat
      exponent alpha approximately 0.5. For the LF domain the contribution to
      epsilon(')(T) from residual ionic impurities follows a linear temperature
      dependence on approaching the isotropic-nematic (I-N) transition. This dependence
      and pretransitional anomalies of electric conductivity and dielectric modulus can
      be associated with the influence of prenematic fluctuations. "Linear" dielectric
      studies were supported by the static nonlinear dielectric effect measurements,
      which delivered reliable estimations of the temperature of the hypothetical
      continuous phase transition T(*) and the discontinuity of the I-N transition
      DeltaT approximately 1.7 K.

PMID- 16626246
TI  - Phase behavior of polyampholytes from charged hard-sphere chain model.
AB  - A molecular thermodynamic theory is developed for polyampholytes from the coarse
      grained charged hard-sphere chain model. The phase behavior of polyampholytes
      with variations in sequence and chain length is satisfactorily predicted by the
      theory, consistent with simulation results and experimental observations. At a
      fixed chain length, the phase envelope expands as the sequence of charge
      distribution becomes less random. With increasing chain length, the phase
      envelope expands for diblock and random polyampholytes, but shrinks for
      zwitterionic polyampholytes. The predicted critical temperature, density, and
      pressure exhibit scaling relations with chain length for all the three (diblock,
      random, and zwitterionic) polyampholytes.

PMID- 16626247
TI  - Analysis of uncertainties in polymer viscoelastic properties obtained from
      equilibrium computer simulations.
AB  - We critically evaluate the uncertainties in the stress autocorrelation function
      obtained from equilibrium molecular dynamics simulation of model polymer melts.
      This quantity is central to evaluating transport properties, e.g., the complex
      modulus and the viscosity. In contrast to the intuitive expectation that
      simulations have to be run five to six orders of magnitude longer than the chain
      relaxation time to reduce uncertainties to acceptable levels, our analysis shows
      that the majority of the uncertainty is associated with rapidly oscillating
      bonded interactions. These fluctuations occur on time scales which are
      approximately 10(4) times shorter than the relaxation time of a chain of length
      80. Consequently, the effects of these oscillations on the stress autocorrelation
      function can be dramatically reduced by (i) conducting long simulations
      (typically 10(6) times longer than the bond relaxation times or only 10(2) chain
      relaxation times) and (ii) by performing running averages with time windows whose
      time scales are much longer than these oscillations. Conducting such long
      simulations also allows for the accurate determination of the melt viscosity and
      the low-frequency complex modulus, but performing running averages do not impact
      these quantities since they are time integrals of the stress autocorrelation
      function.

PMID- 16626248
TI  - Time-dependent perturbation theory for vibrational energy relaxation and
      dephasing in peptides and proteins.
AB  - Without invoking the Markov approximation, we derive formulas for vibrational
      energy relaxation (VER) and dephasing for an anharmonic system oscillator using a
      time-dependent perturbation theory. The system-bath Hamiltonian contains more
      than the third order coupling terms since we take a normal mode picture as a
      zeroth order approximation. When we invoke the Markov approximation, our theory
      reduces to the Maradudin-Fein formula which is used to describe the VER
      properties of glass and proteins. When the system anharmonicity and the
      renormalization effect due to the environment vanishes, our formulas reduce to
      those derived by and Mikami and Okazaki [J. Chem. Phys. 121, 10052 (2004)]
      invoking the path-integral influence functional method with the second order
      cumulant expansion. We apply our formulas to VER of the amide I mode of a small
      amino-acid like molecule, N-methylacetamide, in heavy water.

PMID- 16626249
TI  - Dynamic coupling between coordinates in a model for biomolecular isomerization.
AB  - To understand a complex reaction, it is necessary to project the dynamics of the
      system onto a low-dimensional subspace of physically meaningful coordinates. We
      recently introduced an automatic method for identifying coordinates that relate
      closely to stable-state commitment probabilities and successfully applied it to a
      model for biomolecular isomerization, the C(7eq)-->alpha(R) transition of the
      alanine dipeptide [A. Ma and A. R. Dinner, J. Phys. Chem. B 109, 6769 (2005)].
      Here, we explore approximate means for estimating diffusion tensors for systems
      subject to restraints in one and two dimensions and then use the results together
      with an extension of Kramers theory for unimolecular reaction rates [A.
      Berezhkovskii and A. Szabo, J. Chem. Phys. 122, 014503 (2005)] to show explicitly
      that both the potential of mean force and the diffusion tensor are essential for
      describing the dynamics of the alanine dipeptide quantitatively. In particular,
      the signficance of off-diagonal elements of the diffusion tensor suggests that
      the coordinates of interest are coupled by the hydrodynamic-like response of the
      bath of remaining degrees of freedom.

PMID- 16626250
TI  - Anisotropic colloidal particles interacting with polymers in a good solvent.
AB  - We study the consequences of chain self-avoidance for the interaction between
      nonadsorbing polymers and colloidal particles of anisotropic shape, such as
      ellipsoids, lenses, and dumbbells. In the framework of a field theoretic operator
      expansion for small mesoscopic particles, we obtain exact results for self
      avoiding polymers in d=2 spatial dimensions and we compare ideal and self
      avoiding polymers in 2<d<4. Changing the orientation of a particle, with a given
      size and shape, near a boundary wall requires less free energy if the chains are
      self-avoiding. The distance dependence of the anisotropic interation, mediated by
      the polymers between particle and wall, is changed both qualitatively and
      quantitatively by self-avoidance.

PMID- 16626251
TI  - Structure and effective interactions in polymer nanocomposite melts: an integral
      equation theory study.
AB  - The polymer reference interaction site model from integral equation theory is
      used to investigate the structure and effective interactions in polymer
      nanocomposite melts where strong nanoparticle-monomer interactions are
      principally considered in this work. For finite particle volume fraction, the
      compromise for the interference between polymers and nanoparticles results in an
      optimum particle volume fraction for nanoparticle dispersion in polymer melts. At
      constant particle volume fraction, the effects of degree of polymerization become
      insignificant when it reaches a threshold value, below which quantitative effects
      on the organization states of polymer nanocomposite melts are found and help
      nanoparticles to well disperse in polymer. The aggregation of large nanoparticles
      decreases with the increase of the nanoparticle-monomer attraction strength.
      These observations may provide useful information for the development of new
      polymer materials.

PMID- 16626252
TI  - Semiflexible amphiphilic polymers: cylindrical-shaped, collagenlike, and toroidal
      structures.
AB  - A coarse-grained model is used to study the conformational properties of
      semiflexible polymers with amphiphilic monomer units containing both hydrophilic
      and hydrophobic interaction sites. The hydrophobically driven conformational
      transitions are studied using molecular dynamics simulations for the chains of
      varying stiffness, as characterized by intrinsic Kuhn segment lengths that vary
      over a decade. It is shown that the energy of hydrophobic attraction required for
      the realization of the coil-to-globule transition increases with increasing chain
      stiffness. For rather stiff backbone, the coil-to-globule transition corresponds
      to a first order phase transition. We find that depending on the chain stiffness,
      a variety of thermodynamically stable anisometric chain morphologies are possible
      in a solvent selectively poor for hydrophobic sites of amphiphilic monomer units.
      For flexible chains, the amphiphilic polymer forms a cylindrical globule having
      blob structure with nearly spherical blobs. With increasing stiffness, the number
      of blobs composing the globule decreases and the shape of blobs transforms into
      elongated cylinder. Further increase in stiffness leads to compaction of
      macromolecules into a collagenlike structure when the chain folds itself several
      times and different strands wind round each other. In this state, the
      collagenlike structures coexist with toroidal globules, both conformations having
      approximately equal energies.

PMID- 16626253
TI  - On the extent of polymerization of liquid sulfur at very high temperatures.
AB  - The extent of polymerization of liquid sulfur up to 731 K has been obtained using
      Raman scattering. The data reveal the absence of a maximum in the polymerization
      curve. The obtained results are discussed in the spirit of computer simulations
      that suggest the existence of a maximum which depends on the bond breaking
      energy.

PMID- 16626254
TI  - Loss of chlorine in mass spectra of DCl picked up by water clusters in a beam.
AB  - Water clusters (H(2)O)(n), n<or=16, are produced by supersonic expansion of water
      vapor into vacuum, and then pick up a DCl molecule. The resulting mixed clusters
      are analyzed by electron bombardment ionization mass spectrometry. In all cases
      observed, the chlorine atom is lost in the ionization process, producing a
      deuterated water cluster cation [(H(2)O)(n)D(+)]. This suggests that the chlorine
      atom stays on the surface and has a weaker bond to the host cluster.

PMID- 16626255
TI  - Connection between the direct and mapping forms of a factorized classical
      propagator.

PMID- 16626258
TI  - Syphilis: a forgotten priority.

PMID- 16626259
TI  - Mischievous odds ratios.

PMID- 16626260
TI  - The need for an individual approach to lung cancer treatment.

PMID- 16626263
TI  - Development and demography: a relationship that requires research.

PMID- 16626265
TI  - Teaching clinical skills through videotape review: a randomized trial of group
      versus individual reviews.
AB  - BACKGROUND: Video review is a valuable educational tool for teaching
      communication skills. Many studies have demonstrated its efficacy with individual
      learners, but few studies have addressed its use in a group format. PURPOSE: To
      assess the educational benefits of group versus individual video review of
      standardized patient encounters through the evaluations of 4th-year students at
      the Albert Einstein College of Medicine. METHODS: Students (128) who participated
      in a 7-station, standardized patient, clinical competency exam were randomly
      assigned to an individual or small group video review of selected segments of
      these encounters in 2000-2001. Students filled out an anonymous 13-item
      questionnaire assessing the experience and provided open-ended responses.
      RESULTS: With both review formats, most students had a positive learning
      experience (80%), found it less stressful than they expected (67%), and would not
      have preferred to do the review the other way (84%). Students randomized to
      individual reviews had a significantly higher level of satisfaction with the
      amount of time for the session (91% vs. 78%, p < .05) and the amount of feedback
      they received (95% vs. 79%, p = .01) and were more likely to view the session as
      a positive learning experience (88% vs. 73%, p < .05). Students in the individual
      review format were more likely to choose self-assessed weak segments (63% vs.
      49%, p = .01). Students' comments indicated that they appreciated the value of
      peer review in a group setting. CONCLUSIONS: Although both group reviews and
      individual reviews of videotaped standardized patient encounters were received
      well by the students, there were several statistical differences in favor of the
      individual format.

PMID- 16626266
TI  - What do faculty observe of medical students' clinical performance?
AB  - BACKGROUND: An earlier study of our faculty's evaluation of junior medical
      students indicated that performance ratings were unreliable and reflected 1
      underlying dimension. Other researchers have obtained similar results. PURPOSE:
      The purpose of this study was to identify which aspects of students' clinical
      performance faculty actually observe. METHODS: We analyzed the responses of 9
      faculty members to an open-ended questionnaire concerning which aspects of
      clinical performance attending faculty observe. We also reviewed and summarized
      the written comments of 331 faculty evaluations of third-year medical students.
      RESULTS: Analysis of the questionnaires and evaluations indicated that faculty
      members gauge medical knowledge, professionalism, and clinical reasoning skills
      from direct interaction with students. History-taking and physical examination
      skills are inferred from the quality of verbal presentations. Faculty have little
      basis for evaluating other important aspects of clinical performance.
      CONCLUSIONS: Faculty primarily observe medical students' cognitive skills and
      professionalism. Faculty have little basis for evaluating most other features of
      clinical performance.

PMID- 16626267
TI  - Internal Medicine Clerkship Directors' opinion regarding clinical input in the
      preclinical years: the 2002 CDIM basic science survey results.
AB  - BACKGROUND: Input from both basic science and clinical faculty members is needed
      to promote further integration of medical curricula. PURPOSE: To assess current
      views of clerkship directors about the role and relationship of the basic
      sciences to clinical years in medical education. METHODS: As part of the 2002
      Annual CDIM Survey, questions regarding basic science curriculum were included;
      89 of 123 CDIM members responded (72%). RESULTS: Overall, respondents felt
      participation from both basic science and clinical faculty members is necessary
      to define basic science course content. Nearly 89% of clerkship directors
      indicated curricular review should be collaborative and interdepartmental; 93%
      felt that this review effort should occur frequently. Supporting the growing
      philosophy that the structure of the preclinical years should involve increased
      clinically relevant integration, 58% favored an integrated organ system approach
      rather than the traditional departmental structure (18%). In addition, in order
      of ranking, respondents felt that small group (M = 2.0 +/- 0.9) and problem-based
      learning (M = 2.1 +/- 1.1) are better approaches than the standard lecture format
      (M = 2.8 +/- 1.2). Although clerkship directors recognized the need for increased
      clinical input in the preclinical years, many reported a lack of knowledge
      regarding the amount of clinical exposure students received in the basic science
      years (33%), frequency of peer review of the basic science courses (20%), and who
      performed peer review of the basic science courses at their institution (36%).
      CONCLUSION: Medical clerkship directors believe that basic science education
      should be developed collaboratively, organized by organ system, and presented in
      small groups.

PMID- 16626268
TI  - Preclinical preceptorships in medical school: can curricular objectives be met in
      diverse teaching settings?
AB  - BACKGROUND: Although preclinical preceptorships for medical students during the
      first 2 years are now common, little is known about how well the curricular
      objectives can be met in clinical training sites. PURPOSE: To evaluate whether a
      clinical encounter system can help align preclinical preceptorship experiences
      with the core curriculum. METHODS: Using a PDA documentation system, 27 students
      collected student-preceptor-patient encounter information on all patients (N =
      2,953) during a 2-year clinical training course. We compared Years 1 and 2
      teaching and learning processes, common symptoms seen, and counseling skills
      performed and examined how well these clinical experiences aligned with the
      curricular goals. RESULTS: The majority of encounters in Year 1 involved the
      student observing the preceptor perform a history (47%) or physical exam (40%).
      In Year 2, there was a shift to student and preceptor both participating in the
      history (Year 1, 12%; Year 2, 24%; p = .004) and physical exam (Year 1, 34%; Year
      2, 47%; p = .002). Cardiovascular; pulmonary; and head, eyes, ears, nose, and
      throat examinations were most common in Year 1 and increased in Year 2.
      Genitourinary, gynecologic, and neurological examinations occurred least often,
      and only the neurological examinations increased significantly in Year 2.
      Overall, at least 75% of students could find opportunities in Years 1 and 2 to
      achieve the majority of curricular goals. CONCLUSIONS: Knowing what students
      experience at their preceptor sites is vital for clinical skills course
      evaluation. Student-preceptor-patient encounter data should be used to complement
      other course evaluations to aid curriculum planning and decrease variability in
      student experiences.

PMID- 16626269
TI  - Initial testing of an instrument to measure teacher identity in physicians.
AB  - BACKGROUND: A previous study described 7 elements of teacher identity: intrinsic
      satisfaction from teaching, knowledge and skill about teaching, belonging to a
      community of teachers, receiving rewards for teaching, believing that being a
      doctor means being a teacher, feeling a responsibility to teach, and sharing
      clinical expertise. PURPOSE: To conduct the initial testing of an instrument to
      measure the 7 elements of teacher identity in clinical educators and to consider
      the potential applications of such an instrument. METHODS: A 37-item
      questionnaire was mailed to 153 preceptors of preclinical students. Categories
      reflected the elements of teacher identity listed here. Demographic data were
      collected. Means, alphas, ANOVAs, and paired t tests were calculated. RESULTS: Of
      153 preceptors, 127 (83%) completed the questionnaire. Cronbach's alpha for the
      overall scale and several subscales were high. Salaried physicians and those who
      had completed a faculty development program scored significantly higher on
      several subscales than physicians who volunteered to teach or who did not have
      faculty development. CONCLUSIONS: This study provides preliminary evidence that
      teacher identity can be measured and that preceptors do not respond as a
      homogeneous group. Assessing teacher identity may be helpful to medical schools
      looking to identify and support physicians who teach.

PMID- 16626270
TI  - Academic advancement of authors receiving tutoring from a medical journal.
AB  - BACKGROUND: Although publishing in scientific journals has an educational
      component, the educational role of journals in medicine has not been evaluated.
      PURPOSE: To assess whether tutoring authors in a medical scientific journal could
      be related to their long-term scientific publications and academic advancement.
      METHODS: The study included 47 journal authors who were individually tutored in
      scientific writing and data presentation by the editors of the Croatian Medical
      Journal during the 1991-1995 war years and 47 colleagues the authors identified
      as their academic peers at the time of tutoring. We assessed their published
      articles in scientific journals, citations to these articles, and academic
      advancement, defined as the level of postgraduate education and advancement in
      the academic rank. RESULTS: By 2003, tutored authors published more articles in
      MEDLINE-indexed journals than their academic peers (median = 4, interquartile
      range = 1-9 vs. 1 [0-5], respectively; p = .0265), and received more citations to
      these articles (4 [0-16] vs. 1 [0-6], p = .0275). They also made a significantly
      greater academic advancement, assessed as a score of their academic rank and
      research degree (2 [0-4] vs. 1 [0-2], p = .0369). CONCLUSIONS: Editorial tutoring
      of journal authors can positively influence their long-term academic advancement.
      Journals may have an important teaching role in local academic communities.

PMID- 16626271
TI  - Faculty, students, and actors as standardized patients: expanding opportunities
      for performance assessment.
AB  - BACKGROUND: In an effort to expand preclinical formative assessments, our medical
      school has implemented additional simulated encounters using faculty members and
      students in addition to actors to portray standardized patients (SP). This report
      focuses on the implementation of this strategy. In addition, a preliminary
      evaluation of the fidelity of the simulated clinical encounters based on SP type
      is reported. DESCRIPTION: Three new performance-based assessments were added to
      the second-year curriculum; each was associated with specific content in the
      problem-based learning curriculum. The training of student and faculty SPs was
      modeled after an existing training program for another assessment event.
      EVALUATION: To determine the impact of SP type on students' experiences, 313
      students completed a 9-item anonymous questionnaire after each performance
      assessment; items were rated on a 5-point scale. Faculty members and students who
      were SPs also completed a brief satisfaction questionnaire. Faculty SPs were most
      intimidating to students, but they provided students with the most helpful
      feedback. Students were less anxious when peers were SPs, but they rated the
      encounter as a less valuable simulation. There was no difference in students'
      ratings of confidence in their diagnosis or the extent to which SP type inhibited
      their performance. CONCLUSIONS: Students and faculty benefited from their SP
      experience. A combination of SP types can provide a broad range of cost-effective
      preclinical learning experiences. Students, faculty, and actors as SPs each have
      specific strengths and weaknesses related to cost, training needs, feedback
      quality, and simulation fidelity. The goals of the encounter should guide the
      choice of SP type.

PMID- 16626272
TI  - The effectiveness of a first-year clinical preceptorship on the data collection
      and communication skills of second-year medical students.
AB  - BACKGROUND: Evidence suggests that effective physician communication strongly
      correlates with patient satisfaction and treatment outcome. Unfortunately,
      teaching these skills has been challenging because of 2 major barriers: (a)
      medical students are often too preoccupied with the technical and scientific
      aspects of their curriculum, and (b) it is difficult to expand curricular time.
      DESCRIPTION: To overcome these barriers, an educational intervention that has not
      required additional classroom time was implemented. This first-year preceptorship
      focused on improving data gathering and interpersonal/communication skills.
      EVALUATION: Analysis of the data for the 2 test groups revealed that
      interpersonal and communication skills were modestly higher in the preceptorship
      group. There was no significant difference in data collection in each of the two
      groups. CONCLUSIONS: Combining formal communication skills instruction with an
      early clinical experience may prove to be the most effective approach to
      improving interpersonal, communication, and data gathering skills.

PMID- 16626273
TI  - Educational development program for residency program directors and coordinators.
AB  - BACKGROUND: Residency program directors and program coordinators have increasing
      demands placed on them by accrediting agencies and require educational
      development specifically tailored to their needs. DESCRIPTION: We created,
      piloted, and evaluated an educational development program consisting of 10
      sessions spanning 1 year for program directors and a parallel set of sessions for
      program coordinators. EVALUATION: On average, more than half the residency
      programs participated in the sessions. Programs improved in residency activities
      related to their program's handbook, interviewing, evaluations, rotation
      descriptions, and program evaluation. They did not improve in educational
      scholarly activities. Program directors and coordinators indicated that the
      program improved their skills, and they would recommend the program for others.
      CONCLUSIONS: This 10-session program improved important elements of residency
      education and was favorably received.

PMID- 16626274
TI  - Teaching residents systems-based practice through a hospital cost-reduction
      program: a "win-win" situation.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      Outcome Project challenges residency programs to teach and evaluate competence in
      6 domains, including systems-based practice (SBP). One element of SBP is to
      "practice cost-effective health care ... that does not compromise quality."
      Institutional cost-reduction efforts included targeting laboratory fees by using
      point-of-care testing with an iSTAT machine rather than in the central
      laboratory. Predicted cost savings were 50,000 US dollars per month. Because
      residents are primary users of laboratory resources, the authors engaged them in
      the process and implementation of system redesign. DESCRIPTION: The residents
      identified barriers to use of the iSTAT and solutions to overcome those barriers.
      EVALUATION: As a result of resident solutions, use of the iSTATwent from 40% of
      potential iSTATtests being ordered on the iSTAT to 98%, with an estimated 549,780
      US dollars per year in savings to the hospital. CONCLUSION: Involving residents
      in hospital cost-reduction efforts allows both teaching and evaluation of
      competence in SBP while realizing significant cost savings.

PMID- 16626275
TI  - Narrative review: use of student-generated logbooks in undergraduate medical
      education.
AB  - BACKGROUND: Logbooks are used by clinical clerkships in undergraduate medical
      education as tools for individual student guidance, programmatic evaluation, and
      Liaison Committee on Medical Education (LCME) accreditation. The purpose of this
      narrative review was to summarize the published literature on the form and
      function of logbooks and to review logbook validity and reliability. We performed
      a literature search from 1980 through 2004 and reviewed 50 articles on logbook
      use during clinical clerkships. SUMMARY: Articles were categorized into 5 themes:
      description and feasibility of logbooks (27 articles), accuracy and completeness
      of logbook entries (14 articles), utility to student education (11 articles),
      utility to program evaluation (26 articles), and connecting logbook process
      measures to clerkship outcomes (2 articles). CONCLUSIONS: A feasible and
      acceptable logbook system is an attainable goal, although students usually did
      not complete logbooks unless required. The available literature does not
      establish that logbooks currently in use have sufficient reliability or validity
      to allow for the routine use of the information for program change or
      accreditation purposes. The ideal logbook should be inexpensive, feasible, and
      acceptable to students and should allow rapid collation of accurate, relevant
      data for timely analysis and feedback to the student and clerkship director.

PMID- 16626276
TI  - Mathematics preparation for medical school: do all premedical students need
      calculus?
AB  - BACKGROUND: The premedical student confronts a disparate set of required and
      recommended courses from the various medical schools to which the student might
      apply. SUMMARY: Students may feel compelled to take courses such as calculus even
      though most medical schools do not require it and even though it may not be
      related to either undergraduate academic plans or the core academic needs of the
      typical future physician. CONCLUSIONS: Basic mathematical knowledge--a knowledge
      of algebra, statistics, and overall numeracy--are each more important for most
      future physicians than is the traditional calculus course.

PMID- 16626281
TI  - Cardiac ryanodine receptor phosphorylation: target sites and functional
      consequences.
AB  - A study by Xiao and co-workers in this issue of the Biochemical Journal
      demonstrates PKA (protein kinase A)-dependent phosphorylation of Ser-2030 on the
      cardiac ryanodine receptor (RyR2) that is activated by beta-adrenergic agonists.
      They show that RyR2 phosphorylation at this site is not appreciably altered in
      heart failure samples, but retains PKA-dependence of phosphorylation. They
      contrast this with RyR2 phosphorylation at Ser-2808, a site previously reported
      to be the key and only PKA target site on RyR2. Here Ser-2808 phosphorylation was
      found to be relatively insensitive to either PKA activation or inhibition. These
      results add important new information to a highly controversial field. This issue
      is important because it is increasingly clear that altered regulation of the
      gating of the RyR2 sarcoplasmic reticulum Ca2+-release channel (e.g. by
      phosphorylation) is critically important in mediating altered diastolic
      sarcoplasmic reticulum Ca2+ release. This may contribute to both reduced cardiac
      function and arrhythmogenesis in humans carrying mutations in the RyR2 gene and
      with acquired heart failure of varied aetiology. This study brings some new
      answers, but also raises additional new questions that will require further
      investigation.

PMID- 16626282
TI  - Investigations of the modular structure of bacterial promoters.
AB  - Bacterial RNA polymerase holoenzyme carries different determinants that contact
      different promoter DNA sequence elements. These contacts are essential for the
      recognition of promoters prior to transcript initiation. Here, we have
      investigated how active promoters can be built from different combinations of
      elements. Our results show that the contribution of different contacts to
      promoter activity is critically dependent on the overall promoter context, and
      that certain combinations of contacts can hinder transcription initiation.

PMID- 16626283
TI  - How transcriptional and epigenetic programmes are played out on an individual
      mammalian gene cluster during lineage commitment and differentiation.
AB  - In the post-genomic era, a great deal of work has focused on understanding how
      DNA sequence is used to programme complex nuclear, cellular and tissue functions
      throughout differentiation and development. There are many approaches to these
      issues, but we have concentrated on understanding how a single mammalian gene
      cluster is activated or silenced as stem cells undergo lineage commitment,
      differentiation and maturation. In particular we have analysed the alpha globin
      cluster, which is expressed in a cell-type- and developmental stage-specific
      manner in the haemopoietic system. Our studies include analysis of the
      transcriptional programme that accompanies globin gene activation, focusing on
      the expression of relevant transcription factors and cofactors. Binding of these
      factors to the chromosomal domain containing the alpha globin cluster has been
      characterized by ChIP (chromatin immunoprecipitation). In addition, we have
      monitored the epigenetic modifications (e.g. nuclear position, timing of
      replication, chromatin modification, DNA methylation) that occur as the genes are
      activated (in erythroid cells) or silenced (e.g. in granulocytes) as haemopoiesis
      proceeds. Together, these observations provide a uniquely well-characterized
      model illustrating the mechanisms that regulate and memorize patterns of
      mammalian gene expression as stem cells undergo lineage specification,
      differentiation and terminal maturation.

PMID- 16626284
TI  - MOZ fusion proteins in acute myeloid leukaemia.
AB  - MOZ (monocytic leukaemia zinc finger protein; also known as ZNF220 or MYST3) is a
      member of the MYST family of protein acetyltransferases. Chromosomal
      translocations involving the MOZ gene are associated with AML (acute myeloid
      leukaemia), suggesting that it has a role in haematopoiesis. Recurrent reciprocal
      translocations fuse the MOZ gene [or the gene encoding MORF (MOZ-related factor);
      also known as MYST4] to genes encoding the nuclear receptor co-activators CBP
      [CREB (cAMP response element-binding protein)-binding protein], p300 or the p160
      protein TIF2 (transcription intermediary factor 2). The resulting fusion proteins
      can transform haematopoietic progenitors in vitro, and induce myeloproliferative
      disease in mice. Recent insights into the molecular mechanisms underlying these
      effects indicate that MOZ fusion proteins interfere with the activities of
      transcription factors such as nuclear receptors, p53 and Runx proteins. Our
      studies suggest that subverting the function of cellular CBP and p300 proteins
      may play a key role in this process. Here we review the recent progress in
      understanding the role of MOZ fusion proteins in the aetiology of AML.

PMID- 16626285
TI  - Mechanistic studies of the mRNA transcription cycle.
AB  - We have now completed an atomic crystallographic model of the 12-subunit yeast
      RNA polymerase II in elongation mode, with DNA and RNA in the active-centre
      cleft, and the NTP substrate at the growing end of the RNA. From these studies
      has emerged a detailed three-dimensional view of mRNA elongation. We have
      extended this structural analysis to a polymerase elongation complex bound by the
      transcript cleavage factor TFIIS (transcription factor IIS), which is required
      for polymerase escape from DNA arrest sites. A detailed model of this complex
      reveals a single tuneable active site for RNA polymerization and cleavage, and
      changes in the position of the RNA and polymerase domains, reflecting the dynamic
      nature of the elongation complex. An additional structure of a polymerase CTD (C
      terminal domain) phosphopeptide bound by the 3'-RNA processing factor Pcf11
      provides insights into the coupling of transcription elongation to mRNA
      processing. The structure of the CTD phosphatase Scp1 trapped in an intermediary
      enzymatic state explains CTD dephosphorylation during recycling of the
      polymerase. We also recently reported the first crystal structure of a Mediator
      subcomplex, which reveals an extended helical fold with a conserved hinge.

PMID- 16626286
TI  - Modulation of RNA polymerase core functions by basal transcription factor
      TFB/TFIIB.
AB  - The archaeal basal transcriptional machinery consists of TBP (TATA-binding
      protein), TFB (transcription factor B; a homologue of eukaryotic TFIIB) and an
      RNA polymerase that is structurally very similar to eukaryotic RNA polymerase II.
      This constellation of factors is sufficient to assemble specifically on a TATA
      box-containing promoter and to initiate transcription at a specific start site.
      We have used this system to study the functional interaction between basal
      transcription factors and RNA polymerase, with special emphasis on the post
      recruitment function of TFB. A bioinformatics analysis of the B-finger of
      archaeal TFB and eukaryotic TFIIB reveals that this structure undergoes rapid and
      apparently systematic evolution in archaeal and eukaryotic evolutionary domains.
      We provide a detailed analysis of these changes and discuss their possible
      functional implications.

PMID- 16626287
TI  - The relationship between higher-order chromatin structure and transcription.
AB  - It has generally been assumed that transcriptionally active genes are in an
      'open' chromatin structure and that silent genes have a 'closed' chromatin
      structure. Here we re-assess this axiom in the light of genome-wide studies of
      chromatin fibre structure. Using a combination of sucrose gradient sedimentation
      and genomic microarrays of the human genome, we argue that open chromatin fibres
      originate from regions of high gene density, whether or not those genes are
      transcriptionally active.

PMID- 16626288
TI  - Specialized transcription factories.
AB  - We have previously suggested a model for the eukaryotic genome based on the
      structure of the bacterial nucleoid where active RNA polymerases cluster to loop
      the intervening DNA. This organization of polymerases into clusters--which we
      call transcription 'factories'--has important consequences. For example, in the
      nucleus of a HeLa cell the concentration of soluble RNA polymerase II is
      approximately 1 mM, but the local concentration in a factory is 1000-fold higher.
      Because a promoter can diffuse approximately 100 nm in 15 s, one lying near a
      factory is likely to initiate; moreover, when released at termination, it will
      still lie near a factory, and the movement and modifications (e.g. acetylation)
      accompanying elongation will leave it in an 'open' conformation. Another promoter
      out in a long loop is less likely to initiate, because the promoter concentration
      falls off with the cube of the distance from the factory. Moreover, a long tether
      will buffer it from transcription-induced movement, making it prone to
      deacetylation, deposition of HP1 (heterochromatin protein 1), and incorporation
      into heterochromatin. The context around a promoter will then be self-sustaining:
      productive collisions of an active promoter with the factory will attract factors
      increasing the frequency of initiation, and the longer an inactive promoter
      remains inactive, the more it becomes embedded in heterochromatin. We review here
      the evidence that different factories may specialize in the transcription of
      different groups of genes.

PMID- 16626289
TI  - A role for upstream binding factor in organizing ribosomal gene chromatin.
AB  - Human ribosomal genes are located in NORs (nucleolar organizer regions) on the
      short arms of acrocentric chromosomes. During metaphase, previously active NORs
      appear as prominent chromosomal features termed secondary constrictions, which
      are achromatic in chromosome banding and positive in silver staining. The
      architectural RNA polymerase I transcription factor UBF (upstream binding factor)
      binds extensively across the ribosomal gene repeat throughout the cell cycle.
      Evidence that UBF underpins NOR structure is provided by an examination of cell
      lines in which large arrays of a heterologous UBF binding sequences are
      integrated at ectopic sites on human chromosomes. These arrays efficiently
      recruit UBF even to sites outside the nucleolus, and during metaphase form novel
      silver-stainable secondary constrictions, termed pseudo-NORs, that are
      morphologically similar to NORs.

PMID- 16626290
TI  - Nutrient-regulated gene expression in eukaryotes.
AB  - The recognition of changes in environmental conditions, and the ability to adapt
      to these changes, is essential for the viability of cells. There are numerous
      well characterized systems by which the presence or absence of an individual
      metabolite may be recognized by a cell. However, the recognition of a metabolite
      is just one step in a process that often results in changes in the expression of
      whole sets of genes required to respond to that metabolite. In higher eukaryotes,
      the signalling pathway between metabolite recognition and transcriptional control
      can be complex. Recent evidence from the relatively simple eukaryote yeast
      suggests that complex signalling pathways may be circumvented through the direct
      interaction between individual metabolites and regulators of RNA polymerase II
      mediated transcription. Biochemical and structural analyses are beginning to
      unravel these elegant genetic control elements.

PMID- 16626291
TI  - Chromatin-remodelling factors and the maintenance of transcriptional states
      through DNA replication.
AB  - At the replication fork, nucleosomes, transcription factors and RNA polymerases
      are stripped off the DNA, the DNA double strands are unzipped and DNA methylation
      marks may be erased. Therefore DNA replication is both a 'curse' and 'bliss' for
      the epigenome, as it disrupts its stability by causing chromatin perturbations,
      yet it offers an opportunity to initiate changes in chromatin architecture and
      gene expression patterns, especially during development. Thus the DNA replication
      site is a critical point for regulation. It has become apparent that there is a
      close functional relationship between those factors that regulate transcriptional
      competence and the DNA replication programme. In this review we discuss novel
      insights into how chromatin-remodelling factors at replication sites are involved
      in both the maintenance and regulation of transcriptional states.

PMID- 16626292
TI  - Nucleosome dynamics.
AB  - In the 30 years since the discovery of the nucleosome, our picture of it has come
      into sharp focus. The recent high-resolution structures have provided a wealth of
      insight into the function of the nucleosome, but they are inherently static. Our
      current knowledge of how nucleosomes can be reconfigured dynamically is at a much
      earlier stage. Here, recent advances in the understanding of chromatin structure
      and dynamics are highlighted. The ways in which different modes of nucleosome
      reconfiguration are likely to influence each other are discussed, and some of the
      factors likely to regulate the dynamic properties of nucleosomes are considered.

PMID- 16626293
TI  - Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor
      Elk-1.
AB  - The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in
      response to activation of the MAPK (mitogen-activated protein kinase) pathways.
      This phosphorylation triggers a series of molecular events that convert Elk-1
      from a transcriptionally silent state into a highly active state and then back to
      a basal level. At the same time, activation of the ERK (extracellular-signal
      regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO
      (small ubiquitin-related modifier). As SUMO imparts repressive properties on Elk
      1, ERK-mediated SUMO loss leads to de-repression at the same time as the ERK
      pathway promotes activation of Elk-1. Thus a two-step mechanism is employed to
      convert Elk-1 into its fully activated state. Here, the molecular events
      underlying these changes in Elk-1 status, and the role of PIASxalpha [protein
      inhibitor of activated STAT (signal transducer and activator of transcription)
      xalpha] as a co-activator that facilitates this process, are discussed.

PMID- 16626294
TI  - Non-coding RNA in transcription initiation.
AB  - Diverse classes of non-coding RNAs, including snRNAs (small nuclear RNAs), play
      fundamental regulatory roles in gene expression. For example, 7SK RNA and the
      components of the splicing apparatus U1-U6 snRNAs are implicated in the
      regulation of transcriptional elongation. The first evidence for the involvement
      of RNA in the regulation of transcriptional initiation is now emerging. TFIIH
      (transcription factor IIH), a general transcription initiation factor, appears to
      associate specifically with U1 snRNA, a core splicing component. Reconstituted
      transcription in vitro demonstrates an increase in the rate of formation of the
      first phosphodiester bond by RNA polymerase II in presence of U1 snRNA.
      Reconstituted re-initiation is also stimulated by U1 snRNA. These results suggest
      that U1 snRNA functions in the regulation of transcription by RNA polymerase II
      in addition to its role in RNA processing. The implications of these data extend
      to the development of new technologies that will allow the identification and
      analysis of diverse RNA species present as regulatory components in transcription
      related ribonucleoprotein complexes.

PMID- 16626295
TI  - Activation by c-Myc of transcription by RNA polymerases I, II and III.
AB  - The proto-oncogene product c-Myc can induce cell growth and proliferation. It
      regulates a large number of RNA polymerase II-transcribed genes, many of which
      encode ribosomal proteins, translation factors and other components of the
      biosynthetic apparatus. We have found that c-Myc can also activate transcription
      by RNA polymerases I and III, thereby stimulating production of rRNA and tRNA. As
      such, c-Myc may possess the unprecedented capacity to induce expression of all
      ribosomal components. This may explain its potent ability to drive cell growth,
      which depends on the accumulation of ribosomes. The activation of RNA polymerase
      II transcription by c-Myc is often inefficient, but its induction of rRNA and
      tRNA genes can be very strong in comparison. We will describe what is known about
      the mechanisms used by c-Myc to activate transcription by RNA polymerases I and
      II.

PMID- 16626296
TI  - Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5
      histone acetyltransferase- containing complexes.
AB  - SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a
      CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine
      tract in ataxin-7, a protein of unknown function. Sgf73, a putative yeast
      orthologue of ataxin-7, has been identified as a new component of the yeast SAGA
      (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex, a co-activator required
      for the transcription of a subset of RNA polymerase II-dependent genes. We show
      here that ataxin-7 is an integral component of mammalian SAGA-like complexes,
      i.e. the TFTC [TBP (TATA-binding protein)-free TAF (TBP-associated factor)
      complex] and the STAGA (SPT3/TAF9/GCN5 acetyltransferase) complex. In agreement
      with this, immunoprecipitation of ataxin-7 retained a histone acetyltransferase
      activity characteristic of TFTC-like complexes. Moreover, polyglutamine expansion
      in ataxin-7 did not affect its incorporation into TFTCs/STAGA complexes purified
      from cells from a SCA7 patient. We demonstrate here that ataxin-7 is the human
      orthologue of a the yeast SAGA Sgf73 subunit, and is a bona fide subunit of human
      TFTC-like transcriptional complexes.

PMID- 16626297
TI  - Regulation of NF-kappaB function.
AB  - In the 20 years since its discovery, research into the NF-kappaB (nuclear factor
      kappaB) family of transcription factors has revealed an amazing diversity of
      functions. NF-kappaB proteins are regulators of the immune, inflammatory, stress,
      proliferative and apoptotic responses of a cell to a very large number of
      different stimuli. NF-kappaB complexes can be found in all cell types, indicating
      that the number of different contexts in which NF-kappaB can become induced is
      enormous. Moreover, many reports suggest apparently opposing or contradictory
      functions for NF-kappaB. It is clear that it is not simply enough to understand
      the pathways leading to nuclear localization and DNA binding of NF-kappaB
      subunits. It is also important that we comprehend the regulation of NF-kappaB
      subunit functionality if we are to understand the NF-kappaB pathway as a whole.
      These issues include the mechanisms controlling the specificity and timing of
      genes regulated by NF-kappaB under particular circumstances. They also include
      the reasons why NF-kappaB subunits can sometimes repress rather than activate
      transcription and how the NF-kappaB response is integrated with other important
      transcription factor pathways in the cell, such as the induction of the p53
      tumour suppressor following DNA damage or oncogene activation. Understanding the
      mechanisms that regulate NF-kappaB function has important implications for our
      understanding of the role that NF-kappaB subunits play in human inflammatory
      diseases and cancer, and could also impact on the use of future NF-kappaB-based
      clinical therapies.

PMID- 16626298
TI  - The p53 response during DNA damage: impact of transcriptional cofactors.
AB  - Defects in the DNA damage response pathways can lead to tumour development. The
      tumour suppressor p53 is a key player in the DNA damage response, and the precise
      regulation of p53 is critical for the suppression of tumorigenesis. DNA damage
      induces the activity of p53, via damage sensors such as ATM (ataxia
      telangiectasia mutated) and ATR (ataxia telangiectasia-related), which leads to
      the transcriptional regulation of a variety of genes involved in cell cycle
      control and apoptosis. p53 is therefore tightly controlled, and its activity is
      regulated at a multiplicity of levels. An increasing array of cofactors are now
      known to influence p53 activity. Here we will discuss several of the cofactors
      that impact on p53 activity, specifically those involved in the function of the
      two novel p53 cofactors JMY (junction-mediating and regulatory protein) and Strap
      (serine/threonine-kinase-receptor-associated protein).

PMID- 16626299
TI  - The modulation of WTI transcription function by cofactors.
AB  - Wilms' tumour is a paediatric malignancy of the kidneys that affects one in every
      10,000 live births, making it the most common solid tumour in the young. This
      cancer arises due to a failure of the metanephric mesenchyme to differentiate and
      form the kidney filtration units and tubules, which instead undergo uncontrolled
      proliferation. WT1 (Wilms' tumour 1) was identified as a factor that is
      frequently mutated in Wilms' tumours. WT1 plays a central role in the development
      of the genito-urinary organs and also other regions of the embryo. A major
      function of WT1 is to act as a regulator of transcription, controlling the
      expression of genes that are involved in proliferation and differentiation. WT1
      can either activate or repress transcription of its target genes. Thus the
      transcription function of WT1 is highly context-specific, and can be modulated by
      a number of cofactors. Here, the known interaction partners of WT1 and the
      mechanisms by which they modulate WT1 transcription function will be discussed.

PMID- 16626300
TI  - The RNA polymerase I transcription machinery.
AB  - The rRNAs constitute the catalytic and structural components of the ribosome, the
      protein synthesis machinery of cells. The level of rRNA synthesis, mediated by
      Pol I (RNA polymerase I), therefore has a major impact on the life and destiny of
      a cell. In order to elucidate how cells achieve the stringent control of Pol I
      transcription, matching the supply of rRNA to demand under different cellular
      growth conditions, it is essential to understand the components and mechanics of
      the Pol I transcription machinery. In this review, we discuss: (i) the molecular
      composition and functions of the Pol I enzyme complex and the two main Pol I
      transcription factors, SL1 (selectivity factor 1) and UBF (upstream binding
      factor); (ii) the interplay between these factors during pre-initiation complex
      formation at the rDNA promoter in mammalian cells; and (iii) the cellular control
      of the Pol I transcription machinery.

PMID- 16626301
TI  - Fluorescence resonance energy transfer as a method for dissecting in vivo
      mechanisms of transcriptional activation.
AB  - The first step in transcriptional activation of protein-coding genes involves the
      assembly on the promoter of a large PIC (pre-initiation complex) comprising RNA
      polymerase II and a suite of general transcription factors. Transcription is
      greatly enhanced by the action of promoter-specific activator proteins
      (activators) that function, at least in part, by increasing PIC formation.
      Activator-mediated stimulation of PIC assembly is thought to result from a direct
      interaction between the activator and one or more components of the transcription
      machinery, termed the 'target'. The unambiguous identification of direct,
      physiologically relevant in vivo targets of activators has been a considerable
      challenge in the transcription field. The major obstacle has been the lack
      appropriate experimental methods to measure direct interactions with activators
      in vivo. The development of spectral variants of green fluorescent protein has
      made it possible to perform FRET (fluorescence resonance energy transfer)
      analysis in living cells, thereby allowing the detection of direct protein
      protein interactions in vivo. Here we discuss how FRET can be used to identify
      activator targets and to dissect in vivo mechanisms of transcriptional
      activation.

PMID- 16626302
TI  - Core promoter-selective RNA polymerase II transcription.
AB  - The initiation of mRNA synthesis in eukaryotic cells is a complex and highly
      regulated process that requires the assembly of general transcription factors and
      RNAP II (RNA polymerase II; also abbreviated as Pol II) into a pre-initiation
      complex at the core promoter. The core promoter is defined as the minimal DNA
      region that is sufficient to direct low levels of activator-independent (basal)
      transcription by RNAP II in vitro. The core promoter typically extends approx. 40
      bp up- and down-stream of the start site of transcription and can contain several
      distinct core promoter sequence elements. Core promoters in higher eukaryotes are
      highly diverse in structure, and each core promoter sequence element is only
      found in a subset of genes. So far, only TATA box and INR (initiator) element
      have been shown to be capable of directing accurate RNAP II transcription
      initiation independent of other core promoter elements. Computational analysis of
      metazoan genomes suggests that the prevalence of the TATA box has been
      overestimated in the past and that the majority of human genes are TATA-less.
      While TATA-mediated transcription initiation has been studied in great detail and
      is very well understood, very little is known about the factors and mechanisms
      involved in the function of the INR and other core promoter elements. Here we
      summarize our current understanding of the factors and mechanisms involved in
      core promoter-selective transcription and discuss possible pathways through which
      diversity in core promoter architecture might contribute to combinatorial gene
      regulation in metazoan cells.

PMID- 16626303
TI  - Resveratrol inhibits insulin responses in a SirT1-independent pathway.
AB  - Resveratrol mimics calorie restriction to extend lifespan of Caenorhabditis
      elegans, yeast and Drosophila, possibly through activation of Sir2 (silent
      information regulator 2), a NAD+-dependent histone deacetylase. In the present
      study, resveratrol is shown to inhibit the insulin signalling pathway in several
      cell lines and rat primary hepatocytes in addition to its broad-spectrum
      inhibition of several signalling pathways. Resveratrol effectively inhibits
      insulin-induced Akt and MAPK (mitogen-activated protein kinase) activation mainly
      through disruption of the interactions between insulin receptor substrates and
      its downstream binding proteins including p85 regulatory subunit of
      phosphoinositide 3-kinase and Grb2 (growth factor receptor-bound protein 2). The
      inhibitory effect of resveratrol on insulin signalling is also demonstrated at
      mRNA level, where resveratrol reverses insulin effects on phosphoenolpyruvate
      carboxykinase, glucose-6-phosphatase, fatty acid synthase and glucokinase. In
      addition, RNA interference experiment shows that the inhibitory effect of
      resveratrol on insulin signalling pathway is not weakened in cells with reduced
      expression of SirT1, the mammalian counterpart of Sir2. These observations raise
      the possibility that resveratrol may additionally modulate lifespan through
      inhibition of insulin signalling pathway, independently of its activation of
      SirT1 histone deacetylase. Furthermore, the present study may help to explain a
      wide range of biological effects of resveratrol, and provides further insight
      into the molecular basis of calorie restriction.

PMID- 16626304
TI  - Binding of amyloid beta-peptide to ganglioside micelles is dependent on histidine
      13.
AB  - Amyloid beta-peptide (Abeta) is a major component of plaques in Alzheimer's
      disease, and formation of senile plaques has been suggested to originate from
      regions of neuronal membrane rich in gangliosides. Here we demonstrate using NMR
      on 15N-labelled Abeta-(1-40) and Abeta-(1-42) that the interaction with
      ganglioside G(M1) micelles is localized to the N-terminal region of the peptide,
      particularly residues His13 to Leu17, which become more helical when bound. The
      key interaction is with His13, which undergoes a G(M1)-specific conformational
      change. The sialic acid residue of the ganglioside headgroup is important for
      determining the nature of the conformational change. The isolated pentasaccharide
      headgroup of G(M1) is not bound, suggesting the need for a polyanionic surface.
      Binding to heparin confirms this suggestion, since binding is of similar affinity
      but does not produce the same conformational changes in the peptide. A comparison
      of Abeta-(1-40) and Abeta-(1-42) indicates that binding to G(M1) micelles is not
      related to oligomerization, which occurs at the C-terminal end. These results
      imply that binding to ganglioside micelles causes a transition from random coil
      to alpha-helix in the N-terminal region, leaving the C-terminal region
      unstructured.

PMID- 16626305
TI  - Homocysteine stimulates phosphorylation of NADPH oxidase p47phox and p67phox
      subunits in monocytes via protein kinase Cbeta activation.
AB  - Hyperhomocysteinaemia is an independent risk factor for cardiovascular diseases
      due to atherosclerosis. The development of atherosclerosis involves reactive
      oxygen species-induced oxidative stress in vascular cells. Our previous study
      [Wang and O (2001) Biochem. J. 357, 233-240] demonstrated that Hcy (homocysteine)
      treatment caused a significant elevation of intracellular superoxide anion,
      leading to increased expression of chemokine receptor in monocytes. NADPH oxidase
      is primarily responsible for superoxide anion production in monocytes. In the
      present study, we investigated the molecular mechanism of Hcy-induced superoxide
      anion production in monocytes. Hcy treatment (20-100 microM) caused an activation
      of NADPH oxidase and an increase in the superoxide anion level in monocytes (THP
      1, a human monocytic cell line). Transfection of cells with p47phox siRNA (small
      interfering RNA) abolished Hcy-induced superoxide anion production, indicating
      the involvement of NADPH oxidase. Hcy treatment resulted in phosphorylation and
      subsequently membrane translocation of p47phox and p67phox subunits leading to
      NADPH oxidase activation. Pretreatment of cells with PKC (protein kinase C)
      inhibitors Ro-32-0432 (bisindolylmaleimide XI hydrochloride) (selective for
      PKCalpha, PKCbeta and PKCgamma) abolished Hcy-induced phosphorylation of p47phox
      and p67phox subunits in monocytes. Transfection of cells with antisense PKCbeta
      oligonucleotide, but not antisense PKCalpha oligonucleotide, completely blocked
      Hcy-induced phosphorylation of p47phox and p67phox subunits as well as superoxide
      anion production. Pretreatment of cells with LY333531, a PKCbeta inhibitor,
      abolished Hcy-induced superoxide anion production. Taken together, these results
      indicate that Hcy-stimulated superoxide anion production in monocytes is
      regulated through PKC-dependent phosphorylation of p47phox and p67phox subunits
      of NADPH oxidase. Increased superoxide anion production via NADPH oxidase may
      play an important role in Hcy-induced inflammatory response during atherogenesis.

PMID- 16626306
TI  - Two cycles of cisplatin-based chemotherapy for low-volume retroperitoneal stage
      II nonseminomatous germ cell tumours.
AB  - OBJECTIVE: To evaluate the oncological efficacy of reducing cisplatin-based
      chemotherapy to two cycles in patients with low-volume retroperitoneal stage II
      nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: From October
      1988 until January 2004, two cycles of cisplatin-based chemotherapy were
      administered in 59 patients with low-volume retroperitoneal clinical stage II
      NSGCT (retroperitoneal mass of <5 cm in diameter). Regardless of remission
      detected on computed tomography, 6 weeks after chemotherapy the patients had a
      retroperitoneal lymph node dissection (RPLND) to assess residual active tumour or
      mature teratoma (open modified bilateral RPLND until 1992, then laparoscopic
      unilateral template RPLND). RESULTS: The chemotherapy was effective, as no active
      tumour was found in any of RPLND specimens. Mature teratoma was present in
      lymphatic tissue in 23 of 59 patients (39%). In one patient there was a pulmonary
      recurrence, successfully treated with cisplatin-based salvage chemotherapy. One
      patient died from an accident but with no evidence of tumour, and 56 patients
      remained free of disease at a mean follow-up of 98.6 months. No patient died from
      disease. All patients had antegrade ejaculation after laparoscopic RPLND, as did
      89% after open RPLND. CONCLUSION: In this pilot study, the oncological efficacy
      of two cycles of cisplatin-based chemotherapy was favourable, but this approach
      still cannot be recommended as a standard treatment for patients with low-volume
      retroperitoneal stage II disease. RPLND after chemotherapy has diagnostic
      (detecting active tumour) and therapeutic (removing mature teratoma) value and
      can be done laparoscopically. Based on the present results a prospective
      randomized trial seems reasonable.

PMID- 16626307
TI  - Phosphodiesterase 5 in the female pig and human urethra: morphological and
      functional aspects.
AB  - OBJECTIVE: To characterize the distribution of phosphodiesterase 5 (PDE-5), cGMP
      and cGMP-dependent protein kinase I (PKG1), and to evaluate the effect of
      pharmacological inhibition of PDE-5 in isolated preparations of pig and human
      urethra, as the nitric oxide (NO)/cGMP pathway generates the main inhibitory
      signals to reduce resistance in the bladder outlet and urethra during emptying of
      the bladder. MATERIALS AND METHODS: After obtaining ethics committee approval,
      urethral specimens were obtained from three female patients during cystectomy,
      and from young female pigs. The specimens were prepared for immunohistochemical
      investigations and for functional studies in organ baths. Effects of sildenafil,
      vardenafil and tadalafil (1 nm to 30 microm) were studied in l-noradrenaline (1
      microm)-activated or spontaneously contracted preparations, and on relaxations
      induced by electrical-field stimulation (EFS). Levels of cGMP were determined by
      radioimmunoassay. RESULTS: After stimulation with the NO donor, DETA NONO-ate (1
      mm), there was greater cGMP-immunoreactivity (IR) in urethral and vascular smooth
      muscles. There was a wide distribution of cGMP- and vimentin-positive
      interstitial cells between pig urethral smooth muscle bundles. There was also
      cGMP-IR within NO-synthase-IR endothelium. There was PDE-5 IR within the urethral
      and vascular smooth muscle cells, but also in vascular endothelial cells that
      expressed cGMP-IR. In pig and human sections, there was strong PKG1-IR in alpha
      actin-IR urethral smooth muscle cells that also contained IR for cGMP.
      Sildenafil, vardenafil and tadalafil caused mean (sem) concentration-dependent
      relaxations of the pig urethra which, at 30 microm, were 80 (3)% (11 samples), 81
      (5)% (12 samples) and 64 (4)% (10 samples) of the spontaneous tone. The
      relaxation of L-noradrenaline-contracted female human urethra was 100% in
      response to 10 microm sildenafil, and 85 (15)% and 47 (13)% for 30 microm of
      vardenafil and tadalafil, respectively (three samples). Vardenafil or sildenafil
      (30 microm) doubled cGMP levels in pig specimens. There were no effects on cGMP
      levels with tadalafil. EFS (1-32 Hz) caused l-NG-nitroarginine-sensitive
      relaxations of pig urethral muscle that were increased in amplitude and duration
      by PDE-5 inhibition. At 0.1 microm, sildenafil, vardenafil or tadalafil
      significantly prolonged the mean (sem) duration of the relaxation at 4 Hz by 55
      (19)%, 45 (14)% and 51 (12)%, respectively. CONCLUSIONS: PDE-5-, cGMP- and PKG1
      IR is widely distributed in human and pig urethral tissues. Nerve-induced
      relaxations of urethral preparations were enhanced at low concentrations of
      sildenafil, vardenafil and tadalafil, whereas there were direct smooth muscle
      relaxant actions of the PDE-5 inhibitors at high concentrations. Inhibition of
      PDE-5 might be an interesting option to facilitate cGMP-mediated relaxation of
      the outflow region.

PMID- 16626308
TI  - Clinical characteristics of bladder cancer in patients previously treated with
      radiation for prostate cancer.
AB  - OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation
      therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate
      cancer not treated with RT, as such bladder cancer is thought to be more
      aggressive than de novo bladder cancer, and epidemiological studies show a higher
      rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We
      reviewed our records to identify patients who had a diagnosis of bladder cancer
      with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of
      prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage,
      initial pathology, definitive therapy, definitive pathological stage, and disease
      status were recorded. RESULTS: In all, 100 patients were identified who had a
      diagnosis of bladder cancer after a diagnosis of prostate cancer between January
      1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a
      diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and
      34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer,
      56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs
      27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with
      RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P =
      0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer
      is diagnosed later, and is of higher grade, in patients who are irradiated for
      prostate cancer than in those treated with other methods. Patients with prostate
      cancer who are treated with RT should be monitored closely for the presence of
      bladder cancer.

PMID- 16626312
TI  - Guideline statement: management of procedure-related pain in children and
      adolescents.

PMID- 16626313
TI  - Guideline statement: management of procedure-related pain in neonates.

PMID- 16626316
TI  - [The new German educational law for medical schools: the Hamburg concept in
      dermatology and venereology].
AB  - Medical school graduates are required to deal with complex situations in their
      future work which require profound theoretical knowledge as well as many
      practical skills. The University of Hamburg used a new educational law (AappO
      2002) as catalyst to define learning objectives relevant for practice and to
      guarantee a close connection between theory and practice. A newly founded
      curriculum committee with twelve members developed a strategy and structure for
      the new clinical curriculum (KliniCuM) in weekly sessions. The subject
      dermatology and venereology is taught in the thematic block "The Internal and
      External Human Being" in integrated courses with the subjects internal medicine,
      pathology and pharmacology. The teaching modules (introductory lectures, symptom
      oriented lectures, problem-based tutorials and bedside-teaching) are practice
      oriented and teach diseases and skills of dermatology which are important for
      "general medicine". Written and practical exams take place at the end of the
      block. Although there is more required attendance and increased demands on
      students' time, dermatology has received very positive evaluation results.
      Students consider their gain in knowledge and skills as very high. The new
      curriculum in Hamburg could provide helpful orientation for other medical
      faculties in changing their curricula for the subject "dermatology and
      venereology" according to the new educational law.

PMID- 16626317
TI  - [A trip through the signaling pathways of melanoma].
AB  - Many cellular signaling pathways are involved in the development of cancer.
      Depending on the tumor entity, the nature as well as the mode of activation can
      differ. Some signaling pathways frequently show changes as all tumor cells have
      to fulfill some basic requirements such as independence from growth factors or
      insensitivity against apoptosis. In this review, the possibilities of a tumor to
      manipulate signaling pathways to reach these goals are exemplified based on an
      archetypical melanoma cell. In addition, new therapeutic options based on the
      knowledge of signaling pathways will be discussed.

PMID- 16626318
TI  - [Causative agents of onychomycosis--a retrospective study].
AB  - BACKGROUND: Dermatophytes, yeasts and moulds all are potential causative agents
      of onychomycosis. The aim of this study was to determine the percentage of cases
      of onychomycoses caused by each group. In addition, the responsible genus and
      species was identified for each nail infection. PATIENTS AND METHODS: In a
      retrospective study performed at the Department of Dermatology of the Leipzig
      University, 5,077 nail samples from 4,177 patients--2,240 women and 1,937 men-
      with a variety of nail changes--not just onychomycosis--were investigated. 75%
      were toenails, 23% fingernails, and 2% from both sites. RESULTS: Both microscopic
      and/or cultural detection of fungi (dermatophytes, yeasts and moulds) were
      successful in 54% of samples. Causative fungal agents were: 68% dermatophytes,
      29% yeast, and 3% moulds. The most frequently detected dermatophyte species were
      T. rubrum (91%), and T. mentagrophytes (7.7%). Among yeasts, C. parapsilosis
      (42%) was most common,followed by C. guilliermondii (20.1%), C. albicans (14.2%),
      and Trichosporon spp. (10%). Scopulariopsis brevicaularis (43%) was the most
      frequent mould. The percentage of mixed fungal infections was 22%. CONCLUSIONS:
      Dermatophytes, in particular T.rubrum, but also T. mentagrophytes, are the most
      frequently isolated causative agents in onychomycosis. In addition, yeasts may be
      isolated relatively frequently, while moulds are uncommon.

PMID- 16626319
TI  - [Intraoperative labeling of sentinel lymph nodes with a combination of vital dye
      and radionuclide tracer--results in sentinel lymph node-positive patients].
AB  - BACKGROUND: Sentinel lymph node biopsy enhances the accuracy of tumor staging in
      patients with malignant melanoma and can help select candidates for regional
      lymphadenectomy. There are two techniques for identifying the sentinel lymph
      node: intradermal injection of a radionuclide tracer or of a blue dye. We
      evaluated both methods to determine how they can be best utilized to locate a
      sentinel lymph node. PATIENTS AND METHODS: In a retrospective study, 323 patients
      with melanoma (tumor thickness > or = 0.75 mm) who underwent sentinel lymph node
      biopsy after both radionuclide and blue dye injection were evaluated. The
      labeling of lymph nodes showing micrometastasis by histopathological examination
      was determined. RESULTS: 63 patients showed sentinel lymph nodes with
      micrometastasis. All of these nodes (100 %) were labeled with radionuclide
      tracer, but only 90 % with blue dye. In 5 patients, only radionuclide labeling
      identified the histopathologically-positive lymph node. In 36 patients, several
      sentinel lymph nodes were identified, with the histopathologically-positive nodes
      usually showing a higher radioactive signal intensity than the negative ones.
      CONCLUSION: Since in some patients histopathologically-positive lymph nodes are
      only labeled by radionuclide tracer, radionuclide labeling is indispensable for
      locating sentinel lymph nodes. In contrast, labeling with blue dye represents a
      supplementary method, which can simplify the recognition of the sentinel lymph
      node during surgery.

PMID- 16626320
TI  - [Progressive nodular histiocytosis--rare variant of cutaneous non-Langerhans cell
      histiocytosis].
AB  - Progressive nodular histiocytosis is an extremely rare skin disease is clinically
      characterized by the coincidence of two distinct lesions, namely, superficial
      xanthomatous papules up to 5 mm and deep nodules and tumors 1-3 cm.
      Histologically the nodules represent spindle cell xanthogranulomas. We report a
      24-year-old women with these findings. The distinction from other non-Langerhans
      cell histiocytoses, in particular multiple juvenile xanthogranulomas, which may
      be more likely to show spontaneous remission, is somewhat unclear; patients with
      progressive nodular histiocytosis usually follow a serious and disfiguring
      clinical course.

PMID- 16626321
TI  - [Umbilical endometriosis].
AB  - A 40-year-old woman with a history of a growing erythematous nodule in the
      umbilicus was diagnosed histopathologically with endometriosis. This umbilical
      endometriosis occurred spontaneously without any previous surgical procedures.
      The lesion was partially removed surgically; she then entered menopause with a
      spontaneous involution of the residuum during the following months so that
      further invention was not required. Umbilical endometriosis is very rare with an
      estimated incidence of 0.5 to 1% of all patients with endometrial ectopia. As the
      clinical appearance of umbilical endometriosis may share features with a variety
      of other disorders, we discuss the clinical picture and differential diagnostic
      considerations in detail.

PMID- 16626322
TI  - [Stroma-targeted palliative tumor therapy with biomodulators].
AB  - In search of new strategies for the therapy of advanced tumors stroma-targeted
      approaches have been discussed recently, especially antiangiogenic therapies. It
      has turned out that some biomodulating drugs exhibit also effects against tumors
      beyond their original non-oncologic indication. Among these drugs are for example
      thalidomide,COX-2 inhibitors, PPARgamma agonists (thiazolidindiones) and mTOR
      antagonists (rapamycin). The antitumor efficacy of these therapeutics is
      fundamentally based on indirect effects on the stroma of the tumors. Combination
      therapies of these therapeutics seem to be superior to the use of single agents.
      These new biomodulating therapy approaches represent an interesting option for
      the palliative treatment of advanced tumors, especially as a supplement or
      extension of established chemo- and immunotherapeutic therapies, since they can
      be performed in an outpatient setting, the observed side effects are usually
      mild, and the therapies are therefore well accepted by the patients.

PMID- 16626323
TI  - [75-year-old male with rapidly growing nodule on elbow].

PMID- 16626324
TI  - [Brief guidelines: squamous cell carcinoma of the skin, lip and eyelids].

PMID- 16626325
TI  - [Allergic rhinoconjunctivitis. Guidelines of the DGAI in association with the
      DDG].

PMID- 16626327
TI  - Investigating the genetic determinants of cardiovascular disease using candidate
      genes and meta-analysis of association studies.
AB  - Coronary artery disease (CAD) has a polygenic basis, and identification of CAD
      susceptibility genes has the potential to aid the development of new treatments
      and enhance prediction of disease risk. Thus far, the strategy has firstly been
      to choose "candidate" genes coding for important "rate-limiting" proteins in the
      homeostatic systems involved in maintaining cardiovascular health; secondly to
      identify common variants in these candidate genes; thirdly to carry out
      genotyping and statistical analysis using genetic association studies; and
      finally to test the functional effects of the identified variants in vitro and in
      vivo. However, lack of reproducibility of genetic association studies has led to
      uncertainty about the nature and number of genes involved. In part this is
      because many of the studies conducted have not been adequately powered to detect
      small risk effects, or to permit adequate exploration of gene-gene or gene
      environment interactions in a robust manner. Spurious positive and negative
      associations due to type I and type II statistical errors are likely to co-exist
      with real associations in the published literature. By utilising all available
      data to increase statistical power, meta-analysis of genetic association studies
      is increasingly being used to identify genotypic risk with a greater degree of
      precision. Though potentially powerful, this approach may be prone to publication
      bias. Therefore, very large genetic association studies will also be required to
      identify risk genes for CAD. This review lays out the framework for the candidate
      gene approach for CAD and illustrates this with published results from a UK
      prospective study of 3000 middle-aged men.

PMID- 16626328
TI  - An investigation of FRAXA intermediate allele phenotype in a longitudinal sample.
AB  - The FRAXA trinucleotide repeat at Xq27.3 gives rise to fragile X syndrome when
      fully expanded, and both premature ovarian failure (POF) and fragile X tremor and
      ataxia syndrome (FXTAS) when in the premutation range. Reports of phenotypic
      effects extending into the intermediate repeat range are inconsistent but some
      studies suggest that these smaller expansions predispose to special educational
      needs (SEN). This study utilises the Avon Longitudinal Study of Parents and
      Children (ALSPAC) cohort to investigate cognitive and behavioural variables that
      might be associated with FRAXA intermediate alleles. The current study failed to
      find any strong evidence of association of FRAXA intermediate alleles with SEN,
      behavioural problems or cognitive difficulties. However, our findings illustrate
      some of the difficulties encountered in identifying individuals with SEN. The
      power to identify specific components of cognitive and behavioural difficulties
      was reduced due to elective drop-out, which is characteristic of longitudinal
      studies. Our findings demonstrate the non-random loss of participants from this
      cohort and highlight problems that may arise when such data are used in genetic
      association studies.

PMID- 16626329
TI  - Micro-phylogeographic and demographic history of Portuguese male lineages.
AB  - The clinal pattern observed for the distribution of Y-chromosome lineages in
      Europe is not always reflected at a geographically smaller scale. Six hundred and
      sixty-three male samples from the 18 administrative districts of Portugal were
      typed for 25 Y-chromosome biallelic and 15 microsatellite markers, in order to
      assess the degree of substructuring of male lineage distribution. Haplogroup
      frequency distributions, Analysis of Molecular Variance (AMOVA) and genetic
      distance analyses at both Y-SNP and Y-STR levels revealed a general genetic
      homogeneity of Portuguese sub-populations. The traditional division of the
      country in north, central and south, which is usually considered in studies
      addressing questions of the genetic variation distribution in Portugal, was not
      reflected in the Y-haplotype distribution. Instead, just one sub-region
      (Alentejo) stood out due to the presence of high diversity levels and a higher
      number of different lineages, at higher frequencies than in other regions. These
      results are reconciled with the historical evidence available, assuming that from
      prehistorical times down to the end of the medieval period this region harboured
      the most diverse groups of people and, because of economic depression, remained
      relatively isolated from recent homogenisation movements. The finding of a
      broadly homogeneous background for the Portuguese population has vast
      repercussions in forensic, epidemiological and association studies.

PMID- 16626330
TI  - Mitochondrial DNA diversity in the Polish Roma.
AB  - Mitochondrial DNA variability in the Polish Roma population has been studied by
      means of hypervariable segment I and II (HVS I and II) sequencing and restriction
      fragment-length polymorphism analysis of the mtDNA coding region. The mtDNA
      haplotypes detected in the Polish Roma fall into the common Eurasian
      mitochondrial haplogroups (H, U3, K, J1, X, I, W, and M*). The results of
      complete mtDNA sequencing clearly indicate that the Romani M*-lineage belongs to
      the Indian-specific haplogroup M5, which is characterized by three transitions in
      the coding region, at sites 12477, 3921 and 709. Molecular variance analysis
      inferred from mtDNA data reveals that genetic distances between the Roma groups
      are considerably larger than those between the surrounding European populations.
      Also, there are significant differences between the Bulgarian Roma (Balkan and
      Vlax groups) and West European Roma (Polish, Lithuanian and Spanish groups).
      Comparative analysis of mtDNA haplotypes in the Roma populations shows that
      different haplotypes appear to demonstrate impressive founder effects: M5 and H
      (16261-16304) in all Romani groups; U3, I and J1 in some Romani groups.
      Interestingly, haplogroup K (with HVS I motif 16224-16234-16311) found in the
      Polish Roma sample seems to be specific for Ashkenazi Jewish populations.

PMID- 16626331
TI  - Population structure in the Mediterranean basin: a Y chromosome perspective.
AB  - The Mediterranean region has been characterised by a number of pre-historical and
      historical demographic events whose legacy on the current genetic landscape is
      still a matter of debate. In order to investigate the degree of population
      structure across the Mediterranean, we have investigated Y chromosome variation
      in a large dataset of Mediterranean populations, 11 of which are first described
      here. Our analyses identify four main clusters in the Mediterranean that can be
      labelled as North Africa, Arab, Central-East and West Mediterranean. In
      particular, Near Eastern samples tend to separate according to the presence of
      Arab Y chromosome lineages, suggesting that the Arab expansion played a major
      role in shaping the current genetic structuring within the Fertile Crescent.

PMID- 16626332
TI  - Associations between G/A1229, A/G3944, T/C30875, C/T48200 and C/T65013 genotypes
      and haplotypes in the vitamin D receptor gene, ultraviolet radiation and
      susceptibility to prostate cancer.
AB  - Ultraviolet radiation (UVR) may protect against prostate cancer via a mechanism
      involving vitamin D. Thus, the vitamin D receptor (VDR) gene is a susceptibility
      candidate, though published data are discrepant. We studied the association of
      prostate cancer risk with five VDR single nucleotide polymorphisms (SNPs):
      G/A(1229) (SNP 1), A/G(3944) (SNP 2), T/C(30875) (SNP 3), C/T(48200) (SNP 4) and
      C/T(65013) (SNP 5), in 430 cancer and 310 benign prostatic hypertrophy (BPH)
      patients. The SNP 2 GG genotype frequency was lower in cancer than BPH patients
      (odds ratio = 0.63, 95% CI = 0.41-0.98, p = 0.039). SNPs 1 and 2, and SNPs 4 and
      5, were in linkage disequilibrium. Two copies of haplotypes comprising SNPs 1-2,
      G-G (odds ratio = 0.63, p = 0.039), SNPs 2-3 G-C (odds ratio = 0.45, p = 0.008)
      and SNPs 1-2-3 G-G-C (odds ratio = 0.44, p = 0.006), but not SNPs 1-3, G-C (odds
      ratio = 0.81, p = 0.34), were associated with reduced risk (reference, no copies
      of the haplotypes). These associations were observed after stratification of
      subjects by extent of UVR exposure. These data show that SNP 2 GG genotype
      mediates prostate cancer risk, complementing studies reporting this allele is
      protective in malignant melanoma pathogenesis. They further suggest that
      published associations of risk with SNP 1 may result from linkage disequilibrium
      with SNP 2.

PMID- 16626333
TI  - Modelling germline mosaicism and different new mutation rates simultaneously for
      appropriate risk calculations in families with Duchenne muscular dystrophy.
AB  - For several genetic diseases two biological phenomena have been recognised as
      important: germline mosaicism; and different new mutation rates in males and
      females depending on mutation type. Both principles have been investigated
      separately and their influence on risk estimation in families has been
      exemplified in the literature. The aim of this paper is to present a general
      model that includes mosaicism and different new mutation rates. Mosaicism is
      introduced by defining additional alleles at the disease locus in combination
      with adapted segregation rules. Taking Duchenne muscular dystrophy as an example,
      we derive the conditions which have to be fulfilled for a population in mutation
      selection equilibrium. Our approach describes the model at the population level
      and not in individual subjects. This has the advantage of being able to use well
      known algorithms for the calculation of likelihoods in pedigrees, and to include
      additional diagnostic information such as marker genotypes and carrier deletion
      test results. We demonstrate the impact of the new model on a typical pedigree.
      In families where the patient is not available, the distinction between point
      mutations and deletions is important, since often molecular diagnostic tests for
      females can only screen for deletions. Negative deletion test results can now be
      included in the risk calculations.

PMID- 16626334
TI  - RISCALW: a Windows program for risk calculation in families with Duchenne
      muscular dystrophy.
AB  - RISCALW is a novel convenient Windows program for risk calculation in families
      with Duchenne muscular dystrophy. It is based on an extended genetic model which
      includes germline mosaicism and different new mutation rates depending on sex and
      mutation type. Arbitrary family structures and additional diagnostic information
      such as genotypes from intragenic and flanking genetic markers of the dystrophin
      gene, creatin kinase values, and female deletion test results can be taken into
      account. Comprehensive online help is available. RISCALW has been extensively
      tested in more than 100 families. The user is able to perform risk calculations
      in large families in an easy way, and thus explore the dependence of the results
      on different model assumptions, for example different mutation rates in males and
      females. A detailed handbook and example files are distributed with the program.
      RISCALW is freely available for scientific use at http://www.riscalw.uni-hd.de.

PMID- 16626335
TI  - Obtaining unbiased estimates of tagging SNP performance.
AB  - The use of tagging SNPs (tSNPs) as a cost-effective means of capturing genetic
      diversity is widespread. However, the quality of the tSNPs selected is dependent
      on the initial sample in which they are characterized. If the initial marker set
      is too sparse the tSNPs chosen will capture less information than a naive
      analysis suggests. A simple method has been proposed that should provide a better
      estimate of the performance of tSNPs. It is shown here that this approach is both
      unbiased and accurate, even for small numbers of typed markers. The effect of
      unknown phase is also investigated and it is shown that, excepting very small
      samples, this has little effect on the accuracy of the method.

PMID- 16626336
TI  - Statistical methods for the analysis of genetic association studies.
AB  - This paper applies a retrospective logistic regression model (Prentice, 1976)
      using a sandwich variance estimator (White, 1982; Zeger et al. 1985) to genetic
      association studies in which alleles are treated as dependent variables. The
      validity of switching the positions of allele and trait variables in the
      regression model is ensured by the invariance property of the odds ratio. The
      approach is shown to be able to accommodate many commonly seen designs, matched
      or unmatched alike, having either binary or quantitative traits. The resultant
      score statistic has potentially higher power than those that have previously
      appeared in the genetics literature. As a regression model in general, this
      approach may also be applied to incorporate covariates. Numerical examples
      implemented with standard software are presented.

PMID- 16626337
TI  - Program report: GENECOUNTING support programs.
AB  - We describe a suite of programs which enhance the usability of GENECOUNTING, a
      program for estimating haplotype frequencies in unrelated subjects. The programs,
      called RUNGC, SCANASSOC, COMPGR, SCANGROUP and LDPAIRS, carry out likelihood
      ratio tests and permutation tests to detect differences in haplotype frequencies
      between cases and controls,or between predefined groups, and output likely
      haplotype assignments and tables of linkage disequilibrium statistics between all
      pairs of markers in a dataset.

PMID- 16626338
TI  - Surgical margins for soft tissue sarcoma: size does matter.

PMID- 16626339
TI  - The place of sentinel node biopsy in melanoma after the Multicenter Selective
      Lymphadenectomy Trial.

PMID- 16626340
TI  - Benefits of sentinel node biopsy for melanoma: a review based on interim results
      of the first Multicenter Selective Lymphadenectomy Trial.

PMID- 16626341
TI  - Surgical margin and its influence on survival in soft tissue sarcoma.
AB  - BACKGROUND: The goal of surgeons treating soft tissue sarcoma is to gain local
      control, to avoid risk of local recurrence and to avoid compromise of the
      patient's potential survival. The aim of the investigation was to assess the
      significance of the extent of surgical margin on the chance of death, metastasis
      and local recurrence. METHODS: Two hundred and seventy-nine patients who
      presented with soft tissue sarcoma without metastatic disease were analysed.
      RESULTS: The extent of the surgical margin was not clinically or statistically
      significant in the development of metastatic disease. The presence of a
      contaminated surgical margin led to a significantly higher rate of local
      recurrence (as did a narrow surgical margin less than 1 mm). A margin greater
      than 1 mm allowed a satisfactory outcome in terms of low local recurrence rates.
      In terms of overall survival, the failure to achieve a wide surgical margin (wide
      contaminated margin) led to an increased relative death rate. However, when the
      margin was not contaminated (even if the margin was very close, less than 1 mm),
      the overall survival rate was similar across all groups. Patients who had radical
      resections did poorly; they generally belonged to a group in which palliative
      surgery was carried out, and they showed very high relative metastasis and death
      rates. CONCLUSION: The present study provides statistically significant evidence
      that increasing the width of resection improves local control and overall
      survival.

PMID- 16626342
TI  - Surgical dexterity after a 'night out on the town'.
AB  - BACKGROUND: This study examines the effect of alcohol intake on surgical
      dexterity immediately after and the morning after alcohol intake and minimal
      sleep deprivation by simulating a typical night out on the town. METHODS: Five
      surgeons (all men, aged 31-40 years) were trained on a laparoscopic surgical
      simulator (minimally invasive surgical trainer-virtual reality) to reach a
      desired standard of performance. Three experimental settings were used: (i) a
      control night with no alcohol and full night's sleep; (ii) a sham night out
      (sleep deprived) without alcohol; and (iii) a night out with alcohol ad libitum.
      The parameters recorded were the average time taken to carry out a task, error
      rate, average diathermy time and diathermy (damage) time to main object.
      Comparisons between baseline readings, those in the middle of the night and those
      of the following morning were made by applying ANOVA methods after logarithmic
      transformation of the data. RESULTS: The candidates consumed, on average, 10.33
      units (range, 6-15 units) of alcohol and had 0.86% (range, 0.71-1.1%) of breath
      alcohol levels and an average of 3.75 h (range, 3-5 h) of sleep after a typical
      night out. The morning-after breath alcohol levels were 0%. There was significant
      deterioration in performance, as measured by all indicators, immediately after
      alcohol consumption. The adverse effects on time taken to complete the task and
      total diathermy time were still apparent the morning after. The sham night out
      appeared to affect only 'time parameters'. No significant changes in performance
      were seen in the control setting. CONCLUSION: Both alcohol consumption and sleep
      deprivation adversely affect the ability to carry out surgical procedures. Our
      simulation study suggests that the adverse effects of alcohol intake persist the
      following morning.

PMID- 16626343
TI  - Management of muscle-invasive bladder cancer in Victoria, 1990-1995.
AB  - BACKGROUND: The management and outcomes of muscle-invasive bladder cancer are
      described in this article. METHODS: A retrospective survey of medical
      practitioners involved in the management of bladder cancer was conducted. The
      survey obtained at least 5 years of follow-up data on all patients. The sample
      was taken from the public and private health sectors in Victoria. All were cases
      of muscle-invasive bladder cancer diagnosed between 1990 and 1995. The main
      outcome measures included reported management by staging, treatment and survival.
      RESULTS: Completed questionnaires were returned for 743 (89.6%) of 829 cases. Of
      these, 523 (70.4%) were men, and the mean age was 72.7 years. More than 75% of
      the cases (560) presented with macroscopic haematuria. The majority (696, 94%)
      had transitional cell carcinoma. A variety of treatments were given in various
      sequences, with 231 cases (31.1%) having initial surveillance. Eventually, 303
      cases (40.8%) proceeded to 'definitive' management with either radiotherapy (132,
      17.8%) or cystectomy (171, 23.0%). In addition, chemotherapy was given to 254
      patients (34.2%) at some time. Most patients (613, 82.5%) have subsequently died;
      402 (54%) died from bladder cancer. Crude 5-year survival was 13.0%, and disease
      specific survival was 27.7%. Multivariate analysis identified the following
      predictors of greater disease-specific survival: grade 1 or 2 histopathology (P =
      0.0003), T2 primary (P < 0.0001), N0 disease (P = 0.04), M0 disease (P < 0.0001),
      radiation dose in BED(10) >70 Gy and cystectomy (P < 0.0001). CONCLUSION: Muscle
      invasive bladder cancer in Victoria typically occurs in elderly patients, and a
      notable proportion of these patients do not proceed onto 'definitive' treatment.
      Disease stage, cystectomy and the use of high doses of radiation are associated
      with better outcomes. Chemotherapy was given to approximately one-third of
      patients at some point in their disease management. Our data are similar to
      population-based data from North America, and provide a baseline against which
      potential changes in management of bladder cancer can be compared.

PMID- 16626345
TI  - Benefits of early aggressive management of empyema thoracis.
AB  - BACKGROUND: The end-target of the management of thoracic empyema is to obtain
      early rehabilitation by re-expansion of the trapped lung resulting from
      intrapleural infected material. Our aim was to shorten the hospitalization time
      and to prevent a possible thoracotomy by using video-assisted thoracoscopy
      initially. METHODS: Seventy patients with parapneumonic empyema were
      prospectively studied between January 1997 and June 2004. The patients were
      randomly divided into two groups. In group I (n = 35 patients), a chest tube was
      inserted into the patients after pleural content was evacuated and fibrins were
      debrided using video-assisted thoracoscopy. In group II (n = 35 patients), tube
      thoracostomy was carried out without using a video-assisted thoracoscope. Both
      groups were compared in terms of hospitalization time, open surgery for
      decortication and complications. RESULTS: There was no statistically significant
      difference between the groups from the point of view of age and sex (P > 0.05).
      In group I, 17.1% of the patients underwent open decortication, whereas in group
      II, 37.1% of the patients underwent the same procedure (P < 0.05). Whereas
      average hospital stay in group I was 8.3 days (range, 7-11 days), it was 12.8
      days in group II (range, 10-18 days; P < 0.05). There was one bronchopleural
      fistula in group I, and there was one bronchopleural fistula and one death in
      group II. CONCLUSION: Video-assisted thoracoscopic evacuation and chest tube
      insertion in situ is a new therapeutic approach for pleural empyema that shortens
      hospital stay and reduces the necessity of open decortication.

PMID- 16626346
TI  - Incidental thyroid carcinoma in a large series of consecutive patients operated
      on for benign thyroid disease.
AB  - BACKGROUND: The diagnosis of incidental thyroid carcinoma (ITC) in patients
      operated on for a benign disease is frequent. This study aims to determine both
      its clinical effect and the possibility of identifying this class of patients
      preoperatively. METHODS: A total of 998 consecutive patients (697 women and 301
      men; mean age, 49.5 years) undergoing surgery for benign thyroid pathology in a
      single institution were studied. The mean time between first diagnosis of thyroid
      disease and operation was 9.0 years (range, 0-50 years). All patients underwent
      at least one ultrasonography before surgery, and 678 patients underwent fine
      needle aspiration cytology. Patients with undetermined cytology or follicular
      nodules were excluded from the study. RESULTS: Histology revealed an ITC in 104
      patients (10.4%): 99 had a papillary carcinoma. Mean and median diameters of ITC
      were 1.4 and 0.7 cm, respectively (range, 0.1-7.5 cm). In 43 patients, the tumour
      size was greater than 1 cm, whereas it exceeded 2 cm in 25 patients. Tumours were
      multicentric in 19.8% of the patients and occurred in 8.2% of patients with
      nodular toxic goiter, 8.7% of patients with toxic diffuse goiter and 13.8% of
      patients with multinodular goiter. DISCUSSION: The results confirm the high
      frequency of ITC. ITC was more frequent in euthyroid patients than in thyrotoxic
      patients (P < 0.03). Sex, age, thyroid volume and interval between diagnosis and
      surgery did not significantly influence its incidence. The majority of ITC was
      represented by microcarcinomas, but in approximately 25% of patients, the tumour
      size was greater than 2 cm. The role played by FNAC in excluding malignancies
      proved to be fairly inconclusive.

PMID- 16626348
TI  - Primary peritonitis in adults: is it time to look for a better diagnostic
      classification?
AB  - BACKGROUND: The occurrence of primary peritonitis is rare. The experience of a
      single institution and the definition of this disease are reviewed. METHODS: A
      retrospective audit of primary peritonitis at a single institution was
      undertaken. Age, sex, clinical presentation, initial diagnosis, imaging and blood
      tests, comorbidities, recent medical intervention, surgical treatment and
      operative findings, antibiosis, bacterial isolates, the course of hospital
      treatment and follow up, including later diagnoses, were reviewed. RESULTS: The
      audit was carried out at Christchurch Hospital between January 1998 and March
      2005. A total of 115 patients were identified with a diagnosis of non-specific
      peritonitis, of which five patients were identified with a diagnosis of primary
      peritonitis. All were women aged 22-38 years. Three had undergone a caesarean
      section in the last 3 months. The details of these cases are presented in detail.
      CONCLUSION: Five cases of primary peritonitis are reported, and from a review of
      published work, a classification of primary peritonitis is suggested, which more
      clearly identifies the cause of the disease.

PMID- 16626349
TI  - Predicting iatrogenic gall bladder perforation during laparoscopic
      cholecystectomy: a multivariate logistic regression analysis of risk factors.
AB  - BACKGROUND: Seventeen independent risk factors were examined using multivariate
      logistic regression analysis to develop a profile of patients most likely at risk
      from iatrogenic gall bladder perforation (IGBP) during laparoscopic
      cholecystectomy. METHODS: Since 1989, a prospectively maintained database on 856
      (women, 659; men, 197) consecutive laparoscopic cholecystectomies by a single
      surgeon (R. J. F.) was analysed. The mean age was 48 years (range, 17-94 years).
      The mean operating time was 88 min (range, 25-375 min) and the mean postoperative
      stay was 1 day (range, 1-24 days). There were 311 (women, 214; men, 97) IGBP.
      Seventeen independent variables, which included sex, race, history of biliary
      colic, dyspepsia, history of acute cholecystitis, acute pancreatitis and
      jaundice, previous abdominal surgery, previous upper abdominal surgery, medical
      illness, use of intraoperative laser or electrodiathermy, performance of
      intraoperative cholangiogram, positive intraoperative cholangiogram,
      intraoperative common bile duct exploration, presence of a grossly inflamed gall
      bladder as seen by the surgeon intraoperatively and success of the operation,
      were analysed using multivariate logistic regression for predicting IGBP.
      RESULTS: Multivariate logistic regression analysis against all 17 predictors was
      significant (chi(2) = 94.5, d.f. = 17, P = 0.0001), and the variables male sex,
      history of acute cholecystitis, use of laser and presence of a grossly inflamed
      gall bladder as seen by the surgeon intraoperatively were individually
      significant (P < 0.05) by the Wald chi(2)-test. CONCLUSION: Laparoscopic
      cholecystectomy, using laser, in a male patient with a history of acute
      cholecystitis or during an acute attack of cholecystitis is associated with a
      significantly higher incidence of IGBP.

PMID- 16626350
TI  - Much ado about functional endoscopic sinus surgery.
AB  - BACKGROUND: Reported success rates in endoscopic sinus surgery vary from 74 to
      97%. However, the methods of evaluation and the functional endoscopic sinus
      surgery (FESS) techniques are not standard in these series. In our practice, some
      patients failed to attend the 3-monthly follow up claiming all was well. With
      this experience, the aim of this study is to document a standard minimal
      technique with minimal follow up, which may be applicable to selected patients.
      METHODS: An open prospective clinical trial was conducted. A total of 102
      selected patients were subjected to minimal FESS surgery and discharged after a 3
      month follow up with instructions to return if problems re-ensued. RESULTS: In a
      telephone follow up ranging from 28 to 40 months postoperatively, 12 patients
      could not be traced. All of the other patients expressed satisfaction with the
      results. There were no patients who were dissatisfied with the outcome. However,
      two patients have persisted with postoperative check-up visits on their own
      accord. CONCLUSION: It is possible in selected patients to resort to minimal FESS
      surgery with expectation of a good clinical outcome. It is stressed that, 'rigid
      selection criteria' apply.

PMID- 16626351
TI  - Prospective randomised controlled trial on the role of patient information
      leaflets in obtaining informed consent.
AB  - BACKGROUND: The aim of this study was to determine whether patient information
      leaflets help to improve patient recall during the process of informed consent.
      METHODS: A prospective randomized controlled trial that compared a group of
      patients who were posted a patient information leaflet with those given verbal
      consent only was carried out. The study was conducted at the orthopaedic unit of
      a district general hospital. A total of 110 patients were selected, of whom 57
      were randomly allocated to receive patient information leaflets by post and 53
      were given verbal consent only. The outcome measure was the recall of information
      given to the patient. This was tested on admission by using a questionnaire. Each
      patient was allocated a score out of 10. RESULTS: There was a significant
      difference between the patients in the group that received patient information
      leaflets and those in the group that did not (P < 0.0001; confidence interval,
      2.0-3.1). CONCLUSION: Patient information leaflets are a useful tool for the
      surgeon to improve the recall of the information given to the patient, in order
      to facilitate informed consent.

PMID- 16626353
TI  - Relaxation of the criteria for day surgery laparoscopic cholecystectomy.
AB  - BACKGROUND: For day case laparoscopic cholecystectomy programmes, studies suggest
      that overnight admission may be predicted by the following factors: gall bladder
      wall thickness, patient age over 55 years and previous sphincterotomy. This study
      investigated the effect of relaxing selection for a day surgery laparoscopic
      cholecystectomy programme, by removing these factors from the exclusion criteria.
      METHODS: Between September 2002 and April 2003, patients for elective
      laparoscopic cholecystectomy were considered for day surgery subject to standard
      criteria. For the initial part of the programme, patients were additionally
      excluded according to the risk factors mentioned above. RESULTS: Thirty-three
      patients underwent intended day case procedures. The first 16 were selected
      according to the more rigorous criteria. The latter 17 were significantly older,
      with a significantly higher incidence of gall bladder wall thickening. There were
      seven admissions, three in the former part of the study and four in the latter.
      CONCLUSION: The exclusion criteria described are not necessary for a good same
      day discharge rate.

PMID- 16626354
TI  - Surgery for acute abdominal conditions in intellectually-disabled adults.
AB  - BACKGROUND: Intellectually-disabled patients with acute abdominal conditions are
      susceptible to late diagnosis and adverse outcome due to impaired communication,
      altered behaviour, neurological impairment, associated congenital anomalies,
      variable reaction to pain and drugs and various difficulties in perioperative
      management. The present study aims to present the experience of surgery for acute
      abdominal conditions in intellectually-disabled patients. Various difficulties
      encountered during the management are highlighted and measures to overcome these
      problems are discussed. METHODS: A prospective descriptive population study was
      performed through the prospective collection of data on consecutive
      intellectually-disabled adults operated for acute abdominal conditions over a 5
      year period. Study parameters included demographic details, clinical
      presentation, diagnostic modalities, operative findings and outcome in terms of
      morbidity and mortality. RESULTS: Of 19 men and three women with a mean age of
      28.3 years, anorexia, vomiting, and increasing abdominal distension were the most
      common presenting features. History of pica was available in 36.4% of patients.
      Intestinal obstruction, acute appendicitis, volvulus and pseudo-obstruction of
      the colon were the most frequently encountered conditions. Postoperative
      morbidity and mortality were 33 and 23%, respectively. CONCLUSION: Intellectually
      disabled patients demand particular clinical expertise owing to various
      difficulties inherent to their mental and physical disabilities. Short history,
      anorexia, vomiting and abdominal distension should make the clinician aware of
      the possibility of an acute abdominal condition. History of pica should be
      considered a serious clinical correlate. A high index of clinical suspicion,
      intensive perioperative care and low threshold for an early operation are
      recommended to reduce the higher morbidity and mortality figures.

PMID- 16626355
TI  - Mammary duct fistulae: classification and management.
AB  - BACKGROUND: The aim of the present study was to review the management of mammary
      duct fistulae and propose a classification that could be useful in planning the
      management of mammary duct fistulae. METHODS: Sixteen women presented with a
      mammary duct fistula, two of whom had two fistulae. The data analysed included
      age, smoking habit, previous abscesses, nipple abnormalities, imaging, culture,
      operative technique and histopathological findings. RESULTS: The average follow
      up was 28 months, the mean age was 36.5 years and two women were heavy smokers.
      Nipple abnormalities were found in five (32%) patients, the average number of
      abscesses before the presentation was 1.8 and Staphylococcus coagulase negative
      predominated the culture. Eleven (69%) patients underwent total excision of the
      ductal system and fistulous tract using a technique modified by the author. Five
      patients were offered conservative treatment; however, one of the patients
      refused surgical treatment, but was still followed up in the present study.
      Histopathological results revealed periductal mastitis in 10 patients, idiopathic
      granulomatous mastitis in five patients and tuberculous mastitis in one patient.
      CONCLUSION: Deep mammary duct fistulae are directly related to a diseased ductal
      system and should be differentiated from superficial fistulae, which result from
      the infection of the subepidermal mammary glands. Deep fistulae that result from
      periductal mastitis should be treated by total excision of the ductal system in
      conjunction with the fistulous tract under antibiotics to ensure the lowest rate
      of recurrence. The technique used in the present study resulted in negligible
      morbidity and good cosmetic appearance. A trial of conservative treatment should
      be recommended for fistulae resulting from idiopathic granulomatous mastitis;
      however, further studies are required to establish the best treatment.

PMID- 16626357
TI  - Delay to appendicectomy and associated morbidity: a retrospective review.
AB  - BACKGROUND: This retrospective review was undertaken to determine if time between
      presentation and appendicectomy is a factor affecting morbidity and length of
      hospital stay for patients with proven appendicitis. METHODS: The notes of
      patients who underwent an appendicectomy at Wellington Public Hospital, New
      Zealand between June 2002 and February 2004 were retrospectively reviewed. Delay
      from admission until surgery was noted. Other variables recorded were age, sex,
      operation type (laparoscopic or open), white cell count, pulse rate and
      temperature at admission, antibiotic usage, ancillary investigations (e.g.
      ultrasound), operative findings, length of admission and in-hospital
      complications. RESULTS: A total of 480 appendicectomies were carried out. Four
      hundred and fifty-seven (95%) records were retrieved, and 436 (91%) included the
      required information and were analysed. Ninety-one (21%) resected appendices were
      pathologically normal, 275 (63%) were nonperforated, 61 (14%) were perforated and
      9 (2%) had appendicular abscesses. The mean waiting time from admission to
      operation was 14.5 h (range, 1.6-99 h). There were 36 complications in 31 (7%)
      patients. The mean hospital stay was 74.4 h (range, 9.2-372 h). Three hundred and
      forty-five admitted patients had histologically proven appendicitis. Patients who
      waited 12-24 h for their surgery, when compared with those that waited less than
      12 h, did not have a statistically significant difference in either perforation
      rates (P = 0.66) or abscess formation (P = 0.14). There was also no statistically
      significant difference in the postoperative length of hospital stay (P = 0.6) or
      complication rate (P = 0.92) in patients who waited >24 h for their surgery.
      Patients with appendicitis who waited for >24 h (n = 44) had more abscesses (P =
      0.0001). There was also a statistically significant difference in the perforation
      rate (P = 0.0001), postoperative length of stay (P = 0.04) and overall
      complication rate (P = 0.01). CONCLUSION: Time to surgery of up to 24 h does not
      lead to an increase in complicated appendicitis or morbidity. When the time
      exceeds 24 h, there is an increased rate of complicated appendicitis and
      morbidity, including complications that are not directly related to the
      appendicitis.

PMID- 16626358
TI  - Review of patients with peritoneal malignancy treated with peritonectomy and
      heated intraperitoneal chemotherapy.
AB  - BACKGROUND: Peritoneal dissemination of malignancy is usually considered
      incurable. The purpose of the present study was to evaluate the efficacy of
      intraperitoneal chemohyperthermia and cytoreductive surgery. METHODS: The present
      article is a retrospective review of prospectively recorded data in 60 patients
      who underwent 71 peritonectomy procedures between January 1996 and May 2004.
      Hospital records, a database and department notes were studied. Conditions
      treated were pseudomyxoma peritoneii (PMP) and appendiceal cancer (23),
      mesothelioma (7), colorectal cancer (CRC, 15), ovarian cancer (6) and other forms
      of malignancy (9). Following cytoreductive surgery, early postoperative
      intraperitoneal chemotherapy (EPIC) was given in 47 procedures, five with added
      i.v. mitomycin C. In 34 procedures, heated intraperitoneal chemotherapy (HIPEC)
      was administered. A policy change was made from intravenous to intraperitoneal
      mitomycin C chemotherapy in December 2001. Peritoneal cancer index (PCI) was
      calculated for all procedures. RESULTS: Of the procedures, 23 had PCI < or = 10,
      37 had PCI of 11-20, and 11 had PCI > 20. The median operation time was 9 h.
      Blood units transfused and length of hospital stay have declined. Mortality was
      4/60 patients (6.7%), caused by pancytopenia and sepsis. Morbidity occurred in
      28/71 procedures. The 3-year survival rate for the HIPEC group was 71% compared
      with 28% for the no HIPEC group. In the complete excision group, the 3-year
      survival rate was 52% compared with 13% for the incomplete excision group. The 3
      year survival rate for PMP and appendiceal cancer was 74%. The 2-year survival
      rate for ovarian cancer was 67%, mesothelioma 57%, and CRC 50%, respectively.
      CONCLUSIONS: Morbidity is significantly associated with duration of surgery and
      units of blood transfused. Our findings are consistent with the international
      experience in patients treated with combined peritonectomy and HIPEC.

PMID- 16626359
TI  - Evolving strategies for surgical management of carcinomatosis.

PMID- 16626360
TI  - Current controversies in the management of patients with severe traumatic brain
      injury.
AB  - BACKGROUND: Traumatic brain injury is a major cause of mortality and morbidity,
      particularly among young men. The efficacy and safety of most of the
      interventions used in the management of patients with traumatic brain injury
      remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and
      'volume-targeted' management strategies for optimizing cerebrovascular
      haemodynamics and specific interventions, such as hyperventilation, osmotherapy,
      cerebrospinal fluid drainage, barbiturates, decompressive craniectomy,
      therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy.
      METHODS: A review of the literature was performed to examine the evidence base
      behind each intervention. RESULTS: There is no class I evidence to support the
      routine use of any of the therapies examined. CONCLUSION: Well-designed, large,
      randomized controlled trials are needed to determine therapies that are safe and
      effective from those that are ineffective or harmful.

PMID- 16626361
TI  - Palliative and shared care concepts in patients with advanced colorectal cancer.
AB  - Approximately 50% of patients with colorectal cancer (CRC) will eventually die of
      metastatic disease. Effective palliative management can be used within a shared
      care model in CRC to provide optimum symptom control, psychological well-being
      and maintenance of quality of life for patients, their families and carers,
      including bereavement support. Maintenance of realistic hope and early goal
      setting are equally important in end-of-life discussions with patients and
      families. Palliative care should be incorporated early in the course of the
      illness, concurrent with disease-modifying therapies. Within shared care, the
      palliative medicine specialist, surgeon and other members of the
      multidisciplinary team can each bring their own expertise to provide a patient
      centred approach. A case is presented that incorporates some of these principles
      and exemplifies the benefits of contemporary palliative care for patients with
      advanced CRC.

PMID- 16626362
TI  - Requirements for trainee logbooks.
AB  - All trainees are required to keep a logbook as a record of the procedures they
      have carried out during their surgical training. However, the current logbook is
      only a record of work carried out and not of the outcome of the operations. It
      does not prepare the trainee for either a lifetime practice of surgical audit or
      for a lifetime of learning from the audit process. The logbook requirements of
      different training boards vary and consequently, trainees find the keeping of a
      logbook an inconsistent process with ill-defined learning objectives. The Royal
      Australasian College of Surgeons should define what needs to be collected, how
      data should be verified and how experience and learning should be reported, and
      should approve electronic databases that meet logbook standards. The choice of
      database software and format can then be left to the trainee. Although there are
      good examples of electronic logbooks being developed, there is, at present, no
      perfect logbook available. We recommend that all trainees, from the commencement
      of basic surgical training, should keep a logbook that contains the minimum and
      expanded datasets in addition to specific trainee data on supervision and
      learning. In addition to the current reporting format focused on procedural
      casemix and supervision level, quality/outcome reports and a record of learning
      are recommended.

PMID- 16626363
TI  - The surgical trainee log we need: minimum of work, maximum of output.
AB  - BACKGROUND: The objective of this study was to design a trainee logbook suitable
      for both surgical training and surgical audit. The fields of the logbook should
      conform to both the current requirements for surgical trainee logbooks and the
      minimum and recommended datasets for surgical audit. The database should be able
      to share information with other databases including hospital information systems.
      The current logbook requirements do not include much outcome data. Therefore,
      keeping the logbook does not train the young surgeon to collect all the
      information necessary for surgical audit, particularly the recently promoted
      minimum (12 fields) and recommended (22 fields) datasets. METHODS: An electronic
      logbook was developed as part of the hospital's clinical information system
      (CORDis). Patient identifier information was available in the system and did not
      need to be re-entered (e.g. name, number, date of birth and sex). The trainee
      only input the necessary fields for his/her logbook and was able to derive
      information already available from CORDis on complications, outcome and final
      diagnosis of the patient. RESULTS: Thirteen of 16 trainees used the program over
      a period of 2.5 years, and more than 4600 operative procedures were recorded.
      Information on outcome and complications was included in the logbook, regardless
      of who in the team entered the data. This also facilitated surgical audit
      presentations. Logbook reports for the Advanced Training Board were produced with
      the click of a mouse rather than by spending a whole weekend counting items in
      the operation register at the end of a 6-month rotation. This system could be
      used at different hospitals or the data can be exported to another database
      including databases on a hand-held device. CONCLUSION: The logbook contains all
      the data for reporting to the Specialty Training Board and Surgical Audit.
      Duplication of data entry was reduced, and presentation of unit/trainee surgical
      audits was facilitated. The data can be exchanged with other common databases
      when the trainee rotates out of Geelong.

PMID- 16626365
TI  - Unusual mass in the parapharyngeal space: a Warthin's tumour.
AB  - Parapharyngeal space (PPS) tumours are uncommon and can be a diagnostic challenge
      as the presenting symptoms are often vague and non-specific. Most of the PPS
      tumours are salivary tumours (pleomorphic adenoma being the most frequent
      diagnosis), and are thought to originate from minor salivary glands or the deep
      lobe of the parotid gland. Warthin's tumour, another benign salivary tumour
      involving the PPS has been rarely reported. A case of bilateral, metachronous
      Warthin's tumour involving the PPS is reported here. PPS Warthin's tumour is a
      very rare condition that if undiagnosed may result in considerable morbidity.

PMID- 16626366
TI  - Airway fire during tracheotomy.
AB  - We report a case of airway fire during surgical tracheotomy using diathermy for
      the incision into the trachea. A literature review of airway fire during
      tracheotomy was carried out, and the management of airway fire is discussed.
      Recommendations are made to prevent this adverse outcome.

PMID- 16626367
TI  - Pancreatic osteoclastoma: immunohistochemical evidence of a reactive
      histiomonocytic origin.

PMID- 16626368
TI  - Unsuspected double gall bladder found during laparoscopic cholecystectomy.

PMID- 16626369
TI  - Phenotypic and genotypic identification of enterococci isolated from canals of
      root-filled teeth with periapical lesions.
AB  - The objectives of the present study were to identify enterococcal species
      isolated from the canals of root-filled teeth with periapical lesions using
      biochemical and molecular techniques, and to investigate the genetic diversity of
      the isolates. Twenty-two Enterococcus strains, isolated from the canals of root
      filled teeth with persisting periapical lesions, were identified to species level
      using rapid ID 32 STREP galleries and partial 16S rDNA sequencing. To subtype the
      strains, genomic DNA from the isolates was analyzed by pulsed field gel
      electrophoresis (PFGE) after digestion with SmaI. Intragenic regions of two
      genes, ace and salA, were sequenced for further differentiation of the isolates.
      All strains were identified as Enterococcus faecalis by both commercial kit and
      partial 16S rDNA sequencing. PFGE with SmaI of 22 isolates demonstrated 18
      macrorestriction profiles, whereas 13 distinct genotypes were identified after
      analysis of the ace and salA composite sequences. Most of the isolates from
      distinct patients had different PFGE profiles. Moreover, in two cases, different
      E. faecalis strains were found in different root-filled teeth from the same
      mouth. E. faecalis was the only enterococcal species isolated from the canals of
      root-filled teeth with periapical lesions. Genetic heterogeneity was observed
      among the E. faecalis isolates following PFGE and sequence-based typing method.
      Furthermore, the genetic diversity within root canal strains was similar to
      previous reports regarding E. faecalis isolates from different clinical and
      geographic origins.

PMID- 16626370
TI  - Arginase activity in a murine macrophage cell line (RAW264.7) stimulated with
      lipopolysaccharide from Actinobacillus actinomycetemcomitans.
AB  - AIMS: The aim of the present study was to determine whether or not
      lipopolysaccharide from Actinobacillus actinomycetemcomitans could stimulate
      arginase activity in a murine macrophage cell line (RAW264.7 cells). METHODS:
      RAW264.7 cells were treated with A. actinomycetemcomitans-lipopolysaccharide or
      lipopolysaccharide from Escherichia coli for 24 h. The effect of polymyxin B, l
      norvaline, dl-norvaline, dexamethasone and cytokines (interferon-gamma and
      interleukin-4) on arginase activity in A. actinomycetemcomitans
      lipopolysaccharide-stimulated cells was also determined. The cells were
      pretreated with anti-CD14, anti -toll-like receptor 2, or anti-toll-like receptor
      4 antibody prior to stimulation with A. actinomycetemcomitans-lipopolysaccharide.
      Arginase activity was determined by a colorimetric assay. RESULTS: A.
      actinomycetemcomitans-lipopolysaccharide stimulated arginase activity in RAW264.7
      cells in a dose-dependent manner, but was less potent than E. coli
      lipopolysaccharide. Polymyxin B and l-norvaline, but not dl-norvaline, blocked
      the arginase activity in A. actinomycetemcomitans-lipopolysaccharide-stimulated
      cells. Dexamethasone and interleukin-4 but not interferon-gamma augmented
      arginase activity in A. actinomycetemcomitans-lipopolysaccharide-stimulated
      cells. Treatment of the cells with anti-CD14 and anti-toll-like receptor 4 but
      not anti-toll-like receptor 2 antibody decreased arginase activity in A.
      actinomycetemcomitans-lipopolysaccharide-stimulated cells. CONCLUSION: The
      results of the present study suggest that lipopolysaccharide from A.
      actinomycetemcomitans via CD14/toll-like receptor 4 complex molecules and the
      regulatory control of glucocorticoid and cytokines may stimulate arginase
      activity in RAW264.7 cells.

PMID- 16626371
TI  - Role of CD4 and CD8 T-cells in the induction of oral tolerance to Actinomyces
      viscosus in mice.
AB  - Mucosal presentation of Actinomyces viscosus results in the induction of antigen
      specific systemic suppressor cells in mice. The aim of the present study was to
      determine the phenotype of the suppressor cells responsible for the induction of
      oral tolerance to low doses of A. viscosus. When CD8 cell-depleted DBA/2 mice
      were intragastrically immunized and systemically immunized with A. viscosus, the
      delayed type hypersensitivity response was suppressed but not the levels of
      antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4(+)
      cells to CD4(+)-depleted mice resulted in suppression of delayed type
      hypersensitivity response but not of the levels of antigen specific serum
      antibodies. In contrast, adoptive transfer of orally immunized CD8(+) cells to
      CD8(+)-depleted mice resulted in partially suppressed delayed type
      hypersensitivity response but significantly inhibited the levels of antigen
      specific serum antibodies. When orally tolerized CD8(+) cells were cocultured
      with systemically immunized CD8(+) cell-depleted spleen cells, splenic specific
      antibodies were inhibited. However, no suppression of splenic specific antibodies
      could be observed in the cultures containing orally tolerized CD4(+) cells and
      systemically immunized CD4(+) cell-depleted spleen cells. The results of the
      present study suggest that oral tolerance of humoral and cellular immunity
      induced by low doses of A. viscosus may be mediated by CD8(+) and CD4(+) cells,
      respectively.

PMID- 16626372
TI  - Inhibitory effects of macrocarpals on the biological activity of Porphyromonas
      gingivalis and other periodontopathic bacteria.
AB  - BACKGROUND/AIMS: Macrocarpals, which are phloroglucinol derivatives contained in
      eucalyptus leaves, exhibit antimicrobial activity against a variety of bacteria
      including oral bacteria. This study examined effects of macrocarpals A, B, and C
      on periodontopathic bacteria, especially Porphyromonas gingivalis. METHODS:
      Macrocarpals A, B, and C were purified from a 60% ethanol-extract of Eucalyptus
      globules leaves. To investigate antibacterial activity, representative
      periodontopathic bacteria were cultured in media with or without various amounts
      of macrocarpals; subsequently, the optical density at 660 nm was measured.
      Macrocarpal inhibition of P. gingivalis Arg- and Lys-specific proteinases was
      assessed by spectrofluorophotometric assay and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis. The effect of macrocarpals on P.
      gingivalis binding to saliva-coated hydroxyapatite beads was examined with (3)H
      labeled P. gingivalis. RESULTS: Growth of P. gingivalis was inhibited more
      strongly than growth of Prevotella intermedia or Prevotella nigrescens and
      Treponema denticola by macrocarpals, however, Actinobacillus
      actinomycetemcomitans and Fusobacterium nucleatum were much more resistant.
      Macrocarpals inhibited P. gingivalis Arg- and Lys-specific proteinases in a dose
      dependent manner. The enzyme-inhibitory effect of macrocarpals was confirmed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis in which
      hemoglobin degradation by P. gingivalis proteinase was inhibited by macrocarpals.
      P. gingivalis binding to saliva-coated hydroxyapatite beads was also strongly
      attenuated by macrocarpals. CONCLUSIONS: Macrocarpals A, B and C demonstrated
      antibacterial activity against periodontopathic bacteria. Among tested bacteria,
      P. gingivalis displayed the greatest sensitivity to macrocarpals; additionally,
      its trypsin-like proteinase activity and binding to saliva-coated hydroxyapatite
      beads were inhibited by macrocarpals. These results indicate that eucalyptus leaf
      extracts may be useful as a potent preventative of periodontal disease.

PMID- 16626373
TI  - Antimicrobial susceptibility and molecular analysis of Enterococcus faecalis
      originating from endodontic infections in Finland and Lithuania.
AB  - BACKGROUND/AIMS: Enterococcus faecalis strains with multiple antibiotic
      resistances can cause infections that are difficult to treat. The microbial flora
      in treatment-resistant apical periodontitis is dominated by E. faecalis, and is a
      potential source of infections at other sites. MATERIAL AND METHODS:
      Sensitivities to a range of antibiotics were determined for 59 endodontic E.
      faecalis isolates from Finland and Lithuania. The DNA sequence of the gene
      responsible for the species' intrinsic quinupristin-dalfopristin resistance, lsa,
      was determined from two isolates with diminished resistance. Four pairs of
      isolates from the same root canal were typed by pulsed-field gel electrophoresis.
      RESULTS: A high prevalence of resistance to rifampicin was found, whereas all
      isolates were susceptible or showed intermediate susceptibility to penicillin and
      ampicillin and four isolates were unusually susceptible to cefotaxime. No
      vancomycin or high-level gentamicin resistance was detected. Nine of 59 isolates
      were susceptible to quinupristin-dalfopristin. A fully quinupristin-dalfopristin
      susceptible isolate also susceptible to clindamycin produced a truncated Lsa
      polypeptide, and an isolate with borderline quinupristin-dalfopristin
      susceptibility had mutations proximal to the predicted ribosomal binding site.
      Pulsed-field gel electrophoresis showed that the same root canal could harbor two
      different strains of E. faecalis during the course of the same infection.
      CONCLUSION: Despite the differing antibiotic usage in Finland and Lithuania, E.
      faecalis from endodontic infections in these countries showed similar
      susceptibility patterns with levels of resistance considered typical for the
      species, and decreased resistance to clindamycin and quinupristin-dalfopristin as
      well as lesions in the lsa gene which were similar to those described in other
      clinical isolates.

PMID- 16626374
TI  - Human T-cell responses to oral streptococci in human PBMC-NOD/SCID mice.
AB  - We investigated cellular and humoral immune responses to oral biofilm bacteria,
      including Streptococcus mutans, Streptococcus anginosus, Streptococcus sobrinus,
      and Streptococcus sanguinis, in NOD/SCID mice immunized with human peripheral
      blood mononuclear cells (hu-PBMC-NOD/SCID mice) to explore the pathogenicity of
      each of those organisms in dental and oral inflammatory diseases. hu-PBMC
      NOD/SCID mice were immunized by intraperitoneal injections with the whole cells
      of the streptococci once a week for 3 weeks. FACS analyses were used to determine
      the percentages of various hu-T cell types, as well as intracellular cytokine
      production of interleukin-4 and interferon-gamma. Serum IgG and IgM antibody
      levels in response to the streptococci were also determined by enzyme-linked
      immunosorbent assay. S. anginosus induced a significant amount of the
      proinflammatory cytokine interferon-gamma in CD4(+) and CD8(+) T cells in
      comparison with the other streptococci. However, there was no significant
      differences between the streptococci in interleukin-4 production by CD4(+) and
      CD8(+) T cells after inoculation. Further, S. mutans significantly induced human
      anti-S. mutans IgG, IgG(1), IgG(2), and IgM antibodies in comparison with the
      other organisms. In conclusion, S. anginosus up-regulated Th1 and Tc1 cells, and
      S. mutans led to increasing levels of their antibodies, which was associated with
      the induction of Th2 cells. These results may contribute to a better
      understanding of human lymphocyte interactions to biofilm bacteria, along with
      their impact on dental and mucosal inflammatory diseases, as well as
      endocarditis.

PMID- 16626375
TI  - In vitro antifungal susceptibility to six antifungal agents of 229 Candida
      isolates from patients with diabetes mellitus.
AB  - The most common antifungal drugs in current clinical use for the treatment of
      oral candidosis are polyenes and azoles, mainly used topically. Poor glycaemic
      control in association with other local factors, such as the presence of oral
      dental prostheses, salivary pH, salivary flow rate and tobacco habits, may lead
      to the development of oral candidosis. Topical antifungal agents are frequently
      used to prevent the development of candidal infections in patients with poor
      metabolic control, particularly in the elderly wearing dentures. The aim of this
      study was to assess the antifungal susceptibility of Candida isolates to six
      antifungal agents using a commercially available kit, Fungitest. The isolated
      were collected from patients affected by diabetes mellitus from two different
      geographic localities (London, UK, and Parma, Italy) and from a group of healthy
      non-diabetic subjects. No differences in antifungal susceptibility to the six
      agents tested were observed between Candida isolates from diabetic and non
      diabetic subjects. However, differences were observed between the two
      geographically different diabetes mellitus populations. Oral yeast isolates from
      diabetes mellitus patients in the UK more often displayed resistance or
      intermediate resistance to fluconazole (P=0.02), miconazole (P<0.0001), and
      ketoconazole (P=0.01) than did isolates from diabetes mellitus patients in Italy.
      In addition, more C. albicans isolates were found in diabetic and non-diabetic
      subjects that were susceptible to fluconazole (P=0.0008 and P=0.01, respectively)
      than non-albicans isolates. The difference in the antifungal resistance of
      isolates from the two populations of diabetes mellitus patients may be related to
      differences in the therapeutic management of candidal infections between the two
      centres.

PMID- 16626376
TI  - In vitro evaluation of virulence attributes of Candida spp. isolated from
      patients affected by diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is a common disease found worldwide and it has been
      previously suggested that oral candidal infections may be more frequent or severe
      in patients with this disease. Systemic and local factors may influence the
      balance between the host and yeasts, and favour the transformation of Candida
      isolates from commensal to pathogenic microorganisms. Candida species have
      developed specific virulence mechanisms that confer the ability to colonise host
      surfaces, to invade deeper host tissue, or to evade host defences. Few studies
      have investigated the expression of the virulence attributes of oral Candida
      isolates in patients with diabetes mellitus. MATERIAL AND METHODS: The in vitro
      extracellular proteinase production and the in vitro ability to adhere to
      fibronectin of 229 Candida isolates of two geographic different groups of
      patients with diabetes mellitus and of healthy subjects were assessed. RESULTS:
      Candida isolates of patients with diabetes mellitus expressed a higher ability to
      adhere than those of healthy subjects. Higher levels of adhesion were also
      recorded in patients with a lower oral Candida colonisation. No differences were
      observed in the in vitro expression of extracellular proteinase of Candida
      isolates of patients with diabetes mellitus and those of non-diabetic subjects.
      Isolates of patients with type 2 diabetes mellitus expressed greater levels of
      proteinase than isolates of type 1 diabetes mellitus. CONCLUSIONS: Diabetes
      mellitus could be considered as an additional variable that may influence not
      only oral Candida carriage but also the ability of isolates to enhance the
      expression of virulence attributes.

PMID- 16626377
TI  - Response of human macrophage-like cells to stimulation by Fusobacterium nucleatum
      ssp. nucleatum lipopolysaccharide.
AB  - Monocytes/macrophages are key members of the innate immune system and are present
      in higher numbers in active periodontal lesions than in inactive sites. The aim
      of this study was to characterize the response of human monocyte U937 cells,
      differentiated into adherent macrophages by treatment with phorbol-12-myristate
      13-acetate, to stimulation by Fusobacterium nucleatum ssp. nucleatum
      lipopolysaccharide. Attachment of (3)H-lipopolysaccharide to macrophage-like
      cells was partially inhibited by anti-CD14 and anti-TLR4 polyclonal antibodies.
      Fusobacterial lipopolysaccharide did not cause cell apoptosis or block apoptosis
      induced by camptothecin. Lipopolysaccharide up-regulated the secretion of the pro
      inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis
      factor-alpha as well as the chemokine interleukin-8 by macrophage-like cells. In
      addition, it increased phospholipase C and D activities, which likely contributed
      to the high levels of prostaglandin E(2) detected in the cell culture
      supernatant. Lastly, the amount of matrix metalloproteinase-9 produced by
      macrophage-like cells was significantly increased by the lipopolysaccharide
      treatment. Interestingly, fusobacterial cells acquired matrix metalloproteinase-9
      activity following incubation in the presence of the culture supernatant of
      lipopolysaccharide-stimulated macrophage-like cells. In summary, the
      lipopolysaccharide of F. nucleatum ssp. nucleatum has a large array of biological
      effects on macrophage-like cells. This monocytic responsiveness to
      lipopolysaccharide may be a key regulator of periodontitis.

PMID- 16626378
TI  - Langerhans cells express matrix metalloproteinases 9 and 2 and tissue inhibitors
      of metalloproteinases 1 and 2 in healthy human gingival tissue and in
      periodontitis.
AB  - BACKGROUND: As antigen-presenting cells, Langerhans cells may play an important
      role in the initiation and maintenance of periodontal disease. This study is the
      first report that extends our knowledge of the expression of matrix
      metalloproteinases and their endogenous tissue inhibitors by Langerhans cells in
      healthy and diseased gingival tissues. METHODS: Single and double immunolabeling
      procedures were carried out using monoclonal antibodies against CD1a, matrix
      metalloproteinases 2 and 9, and tissue inhibitors of matrix metalloproteinases 1
      and 2, and analyzed by conventional and confocal microscopes. RESULTS: Langerhans
      cells expressed matrix metalloproteinases 2 and 9, and tissue inhibitors of
      matrix metalloproteinases 1 and 2 in healthy and diseased gingival tissues. The
      tissue inhibitors of matrix metalloproteinase-positive Langerhans cells were
      mainly observed in the upper epithelial layers. Matrix metalloproteinase 9
      positive Langerhans cells were observed especially during periodontitis and in
      the basal epithelial layer or crossing the basement membrane. CONCLUSION: During
      periodontal disease, changes in the expression of matrix metalloproteinases and
      their tissue inhibitors by gingival Langerhans cells could be implicated in the
      migration of the cells towards the connective tissue.

PMID- 16626379
TI  - The Behind-the-Knee test: an efficient model for evaluating mechanical and
      chemical irritation.
AB  - BACKGROUND/PURPOSE: The 'Behind-the-Knee' method (BTK test), using the popliteal
      fossa as a test site, evaluates both the inherent chemical irritation, and the
      potential for mechanical irritation of substrates and products. This approach
      eliminates some of the difficulties of in-use clinical test systems while still
      providing reliable results. In this publication, examples of the results of BTK
      tests on several materials are presented with direct comparisons, where possible,
      with results of in-use clinical testing conducted on the same materials. METHODS:
      In in-use clinical tests, volunteer panelists were provided with catamenial
      products to use in place of their normal product. In the BTK test, samples were
      applied daily to the popliteal fossa using an elastic athletic band. In both
      studies, irritation reactions were scored visually. RESULTS: Levels of irritation
      in the BTK test are consistently higher than those of standard patch tests,
      illustrating the contribution of mechanical irritation to the overall irritant
      potential of materials and products. Repeated tests on identical test materials
      demonstrated that the BTK test results are reproducible. Side-by-side comparisons
      of the BTK test and in-use clinical tests demonstrated that the BTK test produces
      results of similar quality to the in-use clinical. By using several concurrent
      panels with a common test material, it is possible to compare the irritant
      properties of several materials at once. CONCLUSIONS: We have tested over 25
      different materials in over 35 BTK studies. The test method has proven reliable
      and versatile in testing a wide variety of materials, including menstrual pads,
      topsheets, interlabial pads, pantiliners, tampons and lotion coatings on
      products. Unlike in-use clinicals, the BTK test allows the direct comparison of
      two products at one time on the same individual, and is easily adapted to
      investigative programs. It is subject to fewer confounding factors, is much
      easier to implement, has a shorter turnaround time, and is less expensive than in
      use clinical testing. Importantly, unlike standard patch tests, the BTK test
      evaluates both the inherent chemical irritation associated with materials and the
      mechanical irritation owing to friction. Although the BTK test was developed
      using catamenial products, the test system provides a valuable alternative for
      evaluating any material where mechanical irritation may play a role, including
      textiles, facial tissues, baby and adult diapers, and laundry products that may
      leave residues on fabrics.

PMID- 16626380
TI  - Female patients complaining about hair loss: documentation of defective scalp
      hair dynamics with contrast-enhanced phototrichogram.
AB  - BACKGROUND: The complaint of chronic hair loss frequently affects female subjects
      and there is little or no objective technology available in the general
      dermatology or even in the hair clinics to guide the observer in the management
      of the patient. The purpose of this report is to share the results of refined
      hair growth measurements that were collected in 92 female subjects complaining
      about hair loss. METHODS: Clinically they were classified as having a patterned
      hair loss according to Ludwig (L; n=50), diffuse hair loss (D; n=13) or no
      visible hair loss but complaining of hair shedding (N; n=29). Two scalp sites on
      the top of the head and one occipital site were investigated after clipping by
      close-up photography before and after a hair dye (contrast enhancement, CE).
      Forty-eight hours later a new photograph was taken after CE in view of
      phototrichogram analysis (CE-PTG). Finally a last hair clip was performed 30 days
      later and hair thickness and length determined for linear growth measurements
      (LHGR). RESULTS: Herein we confirm that the top of the head shows usually a
      higher hair density than occipital sites, a physiological observation that
      applies both to men and women. From the technological perspective, we also
      document that CE improves hair detection in all sites. Interestingly, in affected
      patients (L and D) the relative increase of hair counts after CE was much higher
      (range +22.4% to +28.3%) compared with apparently unaffected females (N; range
      +8.2% to +9.7%). This increase in hair counts was only due in part to the
      presence of less pigmented thinning hair (thickness less than 40 microm). Such
      thin hairs were found in statistically significantly higher proportions in
      younger patients with mildly severe (grade I) patterned alopecia (Ludwig: L). In
      other patients with hair loss and in more severe forms of patterned alopecia -
      especially in older patients - the thin hair is not detected in abnormal
      proportions. In all sites slower growth rates and decreased anagen percentages
      indicate a defective hair replacement programme distinguishing L patterns from
      diffuse hair loss and from apparently unaffected patients complaining of chronic
      hair loss. Globally, we also noted that increasing age is associated with
      significant regression of scalp hair (decreased hair counts, thinner hair and
      slower LHGR). CONCLUSION: On the basis of the present data together with female
      data from the literature and our own studies in male subjects, we suggest a three
      step mechanism leading to hair loss 1. Shortening of growth phase the hair cycle
      with maintained thick hair, i.e. more frequent hair cycling that leads to more
      hair shedding. 2. Intermittent production of short thin hair, i.e. morphological
      evidence of miniaturisation. 3. Very occasional or almost no hair production,
      i.e. dormant follicles or irreversible follicular atrophy. Depending on the
      genetic background, hormonal microenvironment in the scalp and conditioning of
      individual hair follicle bio-responses, female and male patterned hair loss may
      end up into different phenotypes.

PMID- 16626381
TI  - Validation of scalp coverage scoring methods for scalp hair loss in male pattern
      hair loss (androgenetic alopecia).
AB  - BACKGROUND: Global evaluation of hair loss in male subjects affected by
      androgenetic alopecia has been proposed as a means for monitoring changes over
      time, including placebo-controlled drug efficacy studies. Because of the
      potential impact of subjectivity (e.g. placebo effect) of clinical investigators,
      global photographs (GPs) have been introduced as a more objective record.
      Examination of paired before and after pictures and rating on a seven-point scale
      (from greatly decreased -3 to greatly increased +3) have been historically
      introduced by United States of America (US) experts. METHODS: Based on published
      GPs and original GPs obtained at our clinical research facility, we developed a
      training set in order to allow European Union (EU) observers to practice and
      compare with ratings by the US experts. RESULTS: After training with the seven
      point scale, there was a positive correlation between three US and three EU
      ratings (n=52 paired images from 35 different subjects, r=0.795). The results of
      a test-retest evaluation was performed on 18 paired images from the initial image
      collection by the three EU experts. Correlation r=0.806 and identical scores in
      78% of cases documents a reproducibility similar to the single one US expert
      published data (119 subjects, retest correlation 0.76 with 75% identical
      duplicate ratings). Seventeen subjects taken from a placebo-controlled trial had
      GPs at 6 and 12 months. The average difference between an efficacious drug
      treatment and the placebo were almost similar in the US (0.833) as in the EU
      (0.689) expert panels. We also trained the EU experts in performing the scalp
      coverage scoring (SCS), a novel system for the global evaluation of scalp hair in
      vivo and on GP. SCS was performed on single images (randomised as to time and
      treatment) taken from the same set of 17 paired GPs. This showed a between-group
      difference of 0.055 at 6 months and 0.201 at 12 months, i.e. 5% improved coverage
      in favour of the active group. CONCLUSION: After completion of our study, US and
      trained - calibrated EU experts seem equally valuable in comparing before-after
      GPs. SCS can also be used on GPs and may support the clinical investigator during
      inclusion of test subjects and for real-time efficacy evaluation during the
      trial.

PMID- 16626382
TI  - In vivo imaging of intradermal tattoos by confocal scanning laser microscopy.
AB  - BACKGROUND/AIMS: In vivo confocal laser scanning microscopy (CLSM) is a new
      method for high-resolution imaging of intact skin in situ. Horizontal mapping of
      the outer skin is provided (magnification x 1000). OBJECTIVES: Tattooing is
      popular all over the world; however, tattooed skin has not been studied in using
      CLSM. RESULTS: Tattoos in two volunteers were studied using the Vivascope1500 of
      Lucid Inc. Subepidermal massive deposits of dense, clustered pigment granules up
      to about 3 mum in size corresponding to black tattoos, and more scarce and
      diffuse deposits, corresponding to red, blue and green tattoos, were observed.
      Diffuse pigment granules tended to accumulate in the outer dermis underneath the
      level of the basement membrane zone. CONCLUSIONS: Dermal pigments from tattoos
      can be imaged in vivo using CLSM. This application of CLSM has an important
      future potential for pre-evaluation of tattoos before laser removal, predicting
      good or poor outcome of laser removal.

PMID- 16626383
TI  - Capacitance imaging of the skin surface.
AB  - BACKGROUND/AIMS: A new device allowing recording capacitance images of the skin
      surface was recently presented. Parameters, extracted from the gray-level
      histogram of the images, are tested for a new approach of skin surface hydration
      measurement in comparison with the classical capacitance method. Illustration of
      the interest of having both images and parameters for studying the homogeneity
      and the level of skin surface hydration are presented. METHODS: Software for
      selecting a region of interest from an image and measuring the parameters derived
      from its gray-level histogram was used to characterize skin hydration. RESULTS:
      There is a very close correlation between a Corneometer and the parameters
      extracted from the SkinChip measurements. The importance of having capacitance
      images of skin is demonstrated in case of non-homogeneity of the skin hydration,
      either because of photoaging or following an inflammation process. CONCLUSION:
      Capacitance imaging is a necessary tool for both completely describing and
      quantifying skin surface hydration.

PMID- 16626384
TI  - Ultrasound enhanced skin-lightening effect of vitamin C and niacinamide.
AB  - BACKGROUND/PURPOSE: Cutaneous hyperpigmentation occurs in multiple conditions.
      There is a strong need for the improvement of hyperpigmentation especially among
      Asian women. However, the effect of existing skin-lightening agents is not
      sufficient. One reason attributes to the limited capability of active agents to
      be delivered transepidermally. Ultrasound is one promising approach to enhance
      transepidermal transport. In this work, we investigate the effect of the use of
      high-frequency ultrasound together with coupling gel containing skin-lightening
      agents (ascorbyl glucoside and niacinamide) on facial hyperpigmentation in vivo
      in Japanese women. METHODS: The effect of ultrasound on the absorption of skin
      lightening agents into the stratum corneum was evaluated in a tape-stripping
      method on human forearms in vivo. The skin efficacy was assessed in a facial
      clinical trial involving 60 subjects with hyperpigmentation in a paired design.
      Subjects were assigned to two groups, each group using two treatments (one on
      each facial cheek): (1) skin-lightening gel with ultrasound vs. no treatment or
      (2) skin-lightening gel with ultrasound vs. skin-lightening gel treatment.
      Changes in facial hyperpigmentation were objectively quantified by computer
      analysis and visual grading of high-resolution digital images of the face in
      addition to the subjective assessment via questionnaire. RESULTS: Ultrasound
      radiation enhanced the absorption of skin-lightening agents in the stratum
      corneum in a radiation-time-dependent manner. In the facial clinical trial, use
      of ultrasound radiation together with the skin-lightening gel significantly
      reduced facial hyperpigmented spots compared with both no treatment and skin
      lightening gel alone after 4 weeks. CONCLUSIONS: The data suggest that use of
      high-frequency ultrasound radiation together with skin-lightening gel is
      effective to reduce hyperpigmentation via enhancing transepidermal transport of
      skin-lightening agents.

PMID- 16626385
TI  - Evaluation of the epidermal refractive index measured by optical coherence
      tomography.
AB  - BACKGROUND/AIMS: It has recently been proposed that the refractive index (RI)
      measured by means of optical coherence tomography (OCT) may be a valid measure
      for hydration of skin. In this pilot study, using OCT in vivo, we aimed to
      investigate the interday variability of RI measurements and acute changes of RI
      following the application of a moisturizer. METHODS: Twenty healthy Caucasian
      volunteers were investigated on their forearms using a commercially available OCT
      system (SkinDex 300, ISIS optronics GmbH, Mannheim, Germany) fitted with an
      integrated algorithm for the evaluation of the RI. The interday repeatability of
      the OCT method was determined performing symmetrical measurements on both
      forearms on day 1, 5, 9, and 13. In order to investigate the acute effect of a
      moisturizer on RI, OCT assessments were performed before and 10 min after the
      application of an aqueous lotion with a lipophilic phase. As a control, the
      contralateral site was investigated in the same way, except for the use of
      distilled water instead of the lotion. RESULTS: Assessments of interday
      variability revealed insignificant (P>0.05) variances between the four
      measurement times as expressed in very small repeatability coefficients (right
      arm: 0.039; left arm 0.053) and small coefficients of variance (right arm: 1.02%;
      left arm: 1.38%). With regard to the RIs measured over time, we could not observe
      significant (P>0.05) differences between the two symmetrical anatomic sites
      (mean+/-SD of RI: 1.3893+/-0.0142 (right arm); 1.3875+/-0.0192 (left arm)). The
      acute effect of the moisturizer was indicated by a significant decrease of the RI
      5 min after the application of the lotion (1.399+/-0.01 vs. 1.387+/-0.02;
      difference between means: 0.012; P=0.033; 95% confidence interval: 0.001-0.0023).
      However the control site treated with distilled water did not show significant
      differences between the two measurement times (1.387+/-0.013 vs. 1.391+/-0.023;
      difference between means: -0.004; P=0.57; 95% confidence interval: -0.019-0.011).
      CONCLUSIONS: In this pilot study, we have demonstrated that RI evaluation via OCT
      is a promising technique that may be used for the assessment of skin hydration in
      vivo. However, the direct comparison of OCT with standard methods, ideally such
      as nuclear magnetic resonance spectroscopy, is necessary.

PMID- 16626386
TI  - Comparison of biophysical properties of skin measured by using non-invasive
      techniques in the KM mice following 595 nm pulsed dye, 1064 nm Q-Switched Nd:YAG
      and 1320 nm Nd:YAG laser non-ablative rejuvenation.
AB  - BACKGROUNDS/AIMS: The aim of the study was to compare the changes of the
      biophysical properties and to objectify the effects of 595 nm pulsed dye, 1064 nm
      Q-switched Nd:YAG and 1320 nm Nd:YAG lasers non-ablative rejuvenation by non
      invasive techniques. METHODS: KM mice were used for the study. The 595 nm pulsed
      dye, 1064 nm Q-switched Nd:YAG and 1320 nm Nd:YAG laser treatments were evaluated
      with biophysical parameter measurements including skin elasticity, skin color,
      skin trans-epidermal water loss (TEWL) and skin hydration. RESULTS: All three
      lasers improved the biophysical properties in the skin of KM mice. In skin
      elasticity measurements, the 1064 nm laser treatment showed the lowest ratio
      (0.61+/-0.09) while the 1320 nm laser showed the highest one (0.76+/-0.07) on day
      60. For erythema values, a significant increase was observed immediately after
      the 1064 nm laser treatment (196.67+/-19.17), but the lowest values occurred with
      the 1320 nm laser treatment (189.83+/-16.54). None of the three lasers resulted
      in obvious changes of skin melanin. TEWL increased immediately after laser
      irradiation, then began to recover and decreased 60 days after the 595 and 1064
      nm laser treatments. With the 1320 nm laser treatment the TEWL began to decrease
      from day 7 and obtained the lowest mean values (5.23+/-1.13). The water-holding
      capacity increased initially for the 595 and 1320 nm laser irradiation, while
      decreased for the 1064 nm laser. At day 60 of the experiment, skin hydration
      values in all animals were superior to those of the controls. The 1320 nm laser
      treatment caused the highest ratio (1.29+/-0.26). Both the values of TEWL and
      skin hydration for the 1320 nm laser treated areas differed significantly from
      the other two lasers. CONCLUSIONS: Our data showed the 1064 nm Q-switched Nd:YAG
      laser treatment was most effective in improving the skins' mechanical properties,
      while the 1320 nm Nd:YAG laser can enhance greatly the skin barrier function and
      the water-holding capacity. Moreover, we demonstrated the biophysical properties
      differed considerably between different areas.

PMID- 16626387
TI  - In vivo measurement of water content of the fingernail and its seasonal change.
AB  - BACKGROUND/AIMS: Recently, there has been increasing awareness regardless keeping
      nails in good condition. Maintenance of an optimum water level in the nail plate
      is very important since water content affects the nail condition. However, a
      simple method for in vivo measurement of water in the nail plate quantitatively
      has not been reported. In this study, we applied Near infrared spectroscopy (NIR)
      based prediction of water content of the cut nail plate to in vivo measurement to
      obtain information about the seasonal change of water in the fingernail. METHODS:
      Diffused reflectance spectra of the nail plate of the fingernail were collected
      in the NIR region with an NIR spectrometer in vivo both in summer and winter from
      the same 15 Japanese female subjects. The water content of the nail plate in vivo
      was calculated from the NIR spectrum using partial least square regression
      analysis. RESULTS: It was possible to apply NIR-based prediction of water content
      of the cut nail plate to in vivo measurement. We also found that the water
      content of the nail plate varied from person to person but not with the finger of
      the individual. The average water content of the nail plate was significantly
      lower in winter than in summer (P<0.05). In summer, the water content in the
      double-layered nail tended to be higher than a nail in good condition (P<0.1) and
      significantly lower in the split nail (P<0.05). There was no significant
      difference between the groups in winter. On the contrary, the amount of water
      absorption tended to vary depending on the nail condition. A large amount of
      water was absorbed in the double-layered nail and a small amount in the split
      nail both in summer and winter. CONCLUSION: The water content of the nail plate
      of fingernail was predicted by in vivo measurement using NIR spectrometry.
      Physiological information of the nail in vivo, such as aging and other disorders
      could be obtained by this method.

PMID- 16626388
TI  - Simulation and analysis of optical skin lesion images.
AB  - BACKGROUND/PURPOSE: In order to properly analyse the effectiveness of methods for
      optically differentiating malignant from benign skin lesions, it is necessary to
      have a set of images for which the ground truth is known. However, aspects of the
      ground truth of clinical images such as true lesion boundary position are unknown
      or not known precisely. Therefore, a skin/lesion image simulation with known
      features including boundary location, skin pattern and lesion colour is needed to
      enable accurate assessment of feature estimation algorithms for lesion
      classification. METHODS: In this paper, monochrome and colour skin/lesion images
      are synthesised with known characteristics including boundary, colour and skin
      pattern. Skin pattern is simulated with segmented lines with variations in
      length, orientation and intensity. Skin and lesion textures are modelled by an
      auto-regressive (AR) process. Monochrome skin lesion images are obtained by
      combining monochrome skin and lesion textures under the control of a known lesion
      shape with the addition of skin pattern. Colour skin lesion images are generated
      by mixing coloured skin and lesion textures. Finally, an inflammation area and
      image artefacts such as hair and specular reflection are added. RESULTS: The
      synthesised images provide the image set for evaluating image pre-processing,
      segmentation and skin pattern analysis. The pre-processing includes hair removal
      and specular reflection reduction. An AR model interpolation is suggested for
      hair removal, and multiple illumination processing is developed to decrease
      specular reflection. A fast snake algorithm is extended to detect the boundaries
      of skin lesion and inflammation areas. Skin line direction is detected as a
      feature to measure the disruption of skin pattern caused by lesion. CONCLUSIONS:
      Simulation of monochrome and colour skin/lesion image has been investigated,
      which is an alternative way to provide image set with known characteristics to
      validate image processing algorithms for image pre-processing,
      lesion/inflammation boundary detection and skin pattern analysis.

PMID- 16626389
TI  - Calorie restriction mimetics: an emerging research field.
AB  - When considering all possible aging interventions evaluated to date, it is clear
      that calorie restriction (CR) remains the most robust. Studies in numerous
      species have demonstrated that reduction of calories 30-50% below ad libitum
      levels of a nutritious diet can increase lifespan, reduce the incidence and delay
      the onset of age-related diseases, improve stress resistance, and decelerate
      functional decline. A current major focus of this research area is whether this
      nutritional intervention is relevant to human aging. Evidence emerging from
      studies in rhesus monkeys suggests that their response to CR parallels that
      observed in rodents. To assess CR effects in humans, clinical trials have been
      initiated. However, even if results from these studies could eventually
      substantiate CR as an effective pro-longevity strategy for humans, the utility of
      this intervention would be hampered because of the degree and length of
      restriction required. As an alternative strategy, new research has focused on the
      development of 'CR mimetics'. The objective of this strategy is to identify
      compounds that mimic CR effects by targeting metabolic and stress response
      pathways affected by CR, but without actually restricting caloric intake. For
      example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action
      (metformin), or affect stress signaling pathways (resveratrol), are being
      assessed as CR mimetics (CRM). Promising results have emerged from initial
      studies regarding physiological responses which resemble those observed in CR
      (e.g. reduced body temperature and plasma insulin) as well as protection against
      neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic
      factors). Ultimately, lifespan analyses in addition to expanded toxicity studies
      must be accomplished to fully assess the potential of any CRM. Nonetheless, this
      strategy clearly offers a very promising and expanding research endeavor.

PMID- 16626390
TI  - Free radical generation by skeletal muscle of adult and old mice: effect of
      contractile activity.
AB  - Oxidative modification of cellular components may contribute to tissue
      dysfunction during aging. In skeletal muscle, contractile activity increases the
      generation of reactive oxygen and nitrogen species (ROS). The question of whether
      contraction-induced ROS generation is further increased in skeletal muscle of the
      elderly is important since this influences recommendations on their exercise
      participation. Three different approaches were used to examine whether aging
      influences contraction-induced ROS generation. Hind limb muscles of adult and old
      mice underwent a 15-min period of isometric contractions and we examined ROS
      generation by isolated skeletal muscle mitochondria, ROS release into the muscle
      extracellular fluid using microdialysis techniques, and the muscle glutathione
      and protein thiol contents. Resting skeletal muscle of old mice compared with
      adult mice showed increased ROS release from isolated mitochondria, but no
      changes in the extracellular levels of superoxide, nitric oxide, hydrogen
      peroxide, hydroxyl radical activity or muscle glutathione and protein thiol
      contents. Skeletal muscle mitochondria isolated from both adult and old mice
      after contractile activity showed significant increases in hydrogen peroxide
      release compared with pre-contraction values. Contractions increased
      extracellular hydroxyl radical activity in adult and old mice, but had no
      significant effect on extracellular hydrogen peroxide or nitric oxide in either
      group. In adult mice only, contractile activity increased the skeletal muscle
      release of superoxide. A similar decrease in muscle glutathione and protein thiol
      contents was seen in adult and old mice following contractions. Thus, contractile
      activity increased skeletal muscle ROS generation in both adult and old mice with
      no evidence for an age-related exacerbation of ROS generation.

PMID- 16626391
TI  - Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2)
      links multiple aging and metabolism pathways.
AB  - Molecular genetics in lower organisms has allowed the elucidation of pathways
      that modulate the aging process. In certain instances, evolutionarily conserved
      genes and pathways have been shown to regulate lifespan in mammals as well. Many
      gene products known to affect lifespan are intimately involved in the control of
      energy metabolism, including the fuel sensor AMP-activated protein kinase (AMPK).
      We have shown previously that over-expression of an AMPK alpha subunit in
      Caenorhabditis elegans, designated aak-2, increases lifespan. Here we show the
      interaction of aak-2 with other pathways known to control aging in worms.
      Lifespan extension caused by daf-2/insulin-like signaling mutations was highly
      dependent on aak-2, as was the lifespan extension caused by over-expression of
      the deacetylase, sir-2.1. Similarly, there was partial requirement for aak-2 in
      lifespan extension by mitochondrial mutations (isp-1 and clk-1). Conversely, aak
      2 was not required for lifespan extension in mutants lacking germline stem cells
      (glp-1) or mutants of the eating response (eat-2). These results show that aging
      is controlled by overlapping but distinct pathways and that AMPK/aak-2 represents
      a node in a network of evolutionarily conserved biochemical pathways that control
      aging.

PMID- 16626392
TI  - The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis
      elegans lifespan and regulates genes repressed in multiple long-lived worms.
AB  - The orphan nuclear hormone receptor gene daf-12 in Caenorhabditis elegans plays a
      key role in the regulation of development and determination of adult longevity.
      To understand the effects of daf-12 on aging we characterized the lifespan of
      loss-of-function and gain-of-function daf-12 alleles that have been identified on
      the basis of their effects on dauer development. We find that these mutations
      have opposing effects on longevity and resistance to oxidative and thermal stress
      which makes daf-12 the first gene with alleles that can extend or shorten
      lifespan. We find that the shortened lifespan of the loss-of-function mutation is
      due to accelerated aging in young adulthood rather than an adverse effect of the
      mutation on development. Microarray analysis of worms carrying the two alleles
      revealed a relatively small number of genes differentially expressed between the
      two genotypes. Comparison of the expression profiles with the profiles associated
      with dauer formation and long-lived daf-2 mutants revealed that while the
      profiles are largely different, there is significant overlap among the genes down
      regulated, but not up-regulated, in all profiles. Several of these genes down
      regulated in multiple long-lived worms have known effects on lifespan, and many
      of the genes belong to a family of poorly characterized genes that are strongly
      down-regulated in dauers, daf-2 mutants, and long-lived daf-12 mutants. Our
      results point to daf-12 modulating aging and stress responses in part through the
      repression of specific genes, and emphasize the role that the repression of genes
      that curtail maximal lifespan plays in lifespan determination.

PMID- 16626393
TI  - The aging neurogenic subventricular zone.
AB  - In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell
      niche only 4-5 cell diameters thick. Within this narrow zone, a unique
      microenvironment supports stem cell self-renewal, gliogenesis or neurogenesis
      lineage decisions and tangential migration of newly generated neurons out of the
      SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines.
      Here, we examine the dynamic interplay between SVZ cytoarchitecture and
      neurogenesis through aging. Assembly of high-resolution electron microscopy
      images of corresponding coronal sections from 2-, 10- and 22-month-old mice into
      photomontages reveal a thinning of the SVZ with age. Following a 2-h BrdU pulse,
      we detect a significant decrease in cell proliferation from 2 to 22 months.
      Neuroblast numbers decrease with age, as do transitory amplifying progenitor
      cells, while both SVZ astrocytes and adjacent ependymal cells remain relatively
      constant. At 22 months, only residual pockets of neurogenesis remain and
      neuroblasts become restricted to the anterior dorsolateral horn of the SVZ.
      Within this dorsolateral zone many key components of the younger neurogenic niche
      are maintained; however, in the aged SVZ, increased numbers of SVZ astrocytes are
      found interposed within the ependyma. These astrocytes co-label with markers to
      ependymal cells and astrocytes, form intercellular adherens junctions with
      neighboring ependymal cells, and some possess multiple basal bodies of cilia
      within their cytoplasm. Together, these data reveal an age-related, progressive
      restriction of SVZ neurogenesis to the dorsolateral aspect of the lateral
      ventricle with increased numbers of SVZ astrocytes interpolated within the
      ependyma.

PMID- 16626394
TI  - Overexpression of Abeta is associated with acceleration of onset of motor
      impairment and superoxide dismutase 1 aggregation in an amyotrophic lateral
      sclerosis mouse model.
AB  - Transgenic mice carrying mutant Cu/Zn superoxide dismutase (SOD1) recapitulate
      the motor impairment of human amyotrophic lateral sclerosis (ALS). The amyloid
      beta (Abeta) peptide associated with Alzheimer's disease is neurotoxic. To
      investigate the potential role of Abeta in ALS development, we generated a double
      transgenic mouse line that overexpresses SOD1(G93A) and amyloid precursor protein
      (APP)-C100. The transgenic mouse C100.SOD1(G93A) overexpresses Abeta and shows
      earlier onset of motor impairment but has the same lifespan as the single
      transgenic SOD1(G93A) mouse. To determine the mechanism associated with this
      early-onset phenotype, we measured copper and zinc levels in brain and spinal
      cord and found both significantly elevated in the single and double transgenic
      mice compared with their littermate control mice. Increased glial fibrillary
      acidic protein and decreased APP levels in the spinal cord of C100.SOD1(G93A)
      mice compared with the SOD1(G93A) mice agree with the neuronal damage observed by
      immunohistochemical analysis. In the spinal cords of C100.SOD1(G93A) double
      transgenic mice, soluble Abeta was elevated in mice at end-stage disease compared
      with the pre-symptomatic stage. Buffer-insoluble SOD1 aggregates were
      significantly elevated in the pre-symptomatic mice of C100.SOD1(G93A) compared
      with the age-matched SOD1(G93A) mice, correlating with the earlier onset of motor
      impairment in the C100.SOD1(G93A) mice. This study supports abnormal SOD1 protein
      aggregation as the pathogenic mechanism in ALS, and implicates a potential role
      for Abeta in the development of ALS by exacerbating SOD1(G93A) aggregation.

PMID- 16626395
TI  - Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians:
      implications for the neolymphogenesis at the limit of human life.
AB  - During aging, the thymus undergoes a marked involution that is responsible for
      profound changes in the T-cell compartment. To investigate the capacity of the
      thymus to produce new cells at the limit of human lifespan, we analyzed some
      basic mechanisms responsible for the renewal and maintenance of peripheral T
      lymphocytes in 44 centenarians. Thymic functionality was analyzed by the
      quantification of cells presenting the T-cell receptor rearrangement excision
      circles (TREC). A new method based upon real-time PCR was used, and we found that
      most centenarians (84%) had undetectable levels of TREC+ cells. Six-color
      cytofluorimetric analysis revealed that centenarians had an extremely low number
      of naive T cells; central memory and effector memory T cells were greatly
      increased, while terminally differentiated cells were as numerous as in young
      (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7
      receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA,
      flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in
      centenarian females than males. The presence of TREC+ cells and of very few naive
      T lymphocytes suggests that in centenarians such cells could either derive from
      residues of thymic lymphopoietic islets, or even represent long-living
      lymphocytes that have not yet encountered their antigen. IL-7 could be one of the
      components responsible, among others, for the higher probability of reaching
      extreme ages typical of females.

PMID- 16626396
TI  - Metallothionein antagonizes aging-induced cardiac contractile dysfunction: role
      of PTP1B, insulin receptor tyrosine phosphorylation and Akt.
AB  - Aging is often accompanied by reduced insulin sensitivity and cardiac
      dysfunction. However, the causal relationship between the two remains poorly
      understood. This study was designed to determine the impact of cardiac-specific
      overexpression of antioxidant metallothionein (MT) on aging-associated cardiac
      dysfunction and impaired insulin signaling. Contractile and intracellular Ca(2+)
      properties were evaluated in left ventricular myocytes including peak shortening
      (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS),
      time-to-90% relengthening (TR(90)), fura-2 fluorescence intensity change
      (DeltaFFI) and intracellular Ca(2+) decay rate. Expression of insulin receptor,
      protein-tyrosine phosphatase 1B (PTP1B), phosphorylation of insulin receptor
      (Tyr1146) and Akt were evaluated by Western blot analysis. Aged wild-type FVB and
      MT transgenic mice (26-28 months old) displayed glucose intolerance and
      hyperinsulinemia. Cardiomyocytes from aged FVB mice exhibited prolonged TR(90)
      and intracellular Ca(2+) decay associated with normal PS, +/- dL/dt, TPS and
      DeltaFFI compared with those from young (2-3 months old) mice. Western blot
      analysis revealed reduced Akt expression and insulin (5 mU g(-1))-stimulated Akt
      phosphorylation, elevated PTP1B expression and diminished basal insulin receptor
      tyrosine phosphorylation associated with comparable insulin receptor expression
      in aged FVB mouse hearts. All of these aging-related defects in cardiac
      contractile function and insulin signaling (although not hyperinsulinemia and
      glucose intolerance) were significantly attenuated or ablated by MT transgene.
      These data indicate that enhanced antioxidant defense is beneficial for aging
      induced cardiac contractile dysfunction and alteration in insulin signaling.

PMID- 16626397
TI  - Senescence-associated beta-galactosidase is lysosomal beta-galactosidase.
AB  - Replicative senescence limits the proliferation of somatic cells passaged in
      culture and may reflect cellular aging in vivo. The most widely used biomarker
      for senescent and aging cells is senescence-associated beta-galactosidase (SA
      beta-gal), which is defined as beta-galactosidase activity detectable at pH 6.0
      in senescent cells, but the origin of SA-beta-gal and its cellular roles in
      senescence are not known. We demonstrate here that SA-beta-gal activity is
      expressed from GLB1, the gene encoding lysosomal beta-D-galactosidase, the
      activity of which is typically measured at acidic pH 4.5. Fibroblasts from
      patients with autosomal recessive G(M1)-gangliosidosis, which have defective
      lysosomal beta-galactosidase, did not express SA-beta-gal at late passages even
      though they underwent replicative senescence. In addition, late passage normal
      fibroblasts expressing small-hairpin interfering RNA that depleted GLB1 mRNA
      underwent senescence but failed to express SA-beta-gal. GLB1 mRNA depletion also
      prevented expression of SA-beta-gal activity in HeLa cervical carcinoma cells
      induced to enter a senescent state by repression of their endogenous human
      papillomavirus E7 oncogene. SA-beta-gal induction during senescence was due at
      least in part to increased expression of the lysosomal beta-galactosidase
      protein. These results also indicate that SA-beta-gal is not required for
      senescence.

PMID- 16626399
TI  - Extended phylogeny of equine arteritis virus: division into new subgroups.
AB  - To determine a conclusive phylogeny, equine arteritis viruses from Italy,
      Austria, Hungary, Sweden, South Africa and other parts of the world were analysed
      by reverse-transcription polymerase chain reaction amplification and direct
      sequencing. The nucleotide sequences corresponding to the variable part of the
      large glycoprotein GP5, specified by open reading frame 5, were compared and
      added to a previously published phylogenetic tree in which a clear division
      between 'European' and 'American' type viruses had been established. Adding the
      sequences determined in this study and new sequences retrieved from GenBank
      revealed additional diversity and new subgroups.

PMID- 16626400
TI  - A slide latex agglutination test for the rapid detection of antibodies in serum
      against porcine parvovirus.
AB  - A slide latex agglutination test (LAT) was developed and evaluated to detect
      serum antibodies against porcine parvovirus. Porcine parvovirus antigen was
      obtained by 10% PEG-6000 and 0.5 mol/l sodium chloride precipitation, and
      inactivated by 0.1% methanal. Two per cent suspensions of latex particles (0.5
      0.8 microm) were coated by adding an equal volume of porcine parvovirus antigen
      at 0.34 microg/ml. Repeatability of latex agglutination test was evaluated with a
      panel of 100 sera using the same and different antigen lots. A good agreement
      between LAT and haemagglutination inhibit assay was observed. Because of
      convenience and speed of performance, this method would be used widely in clinic
      examination.

PMID- 16626401
TI  - Comparison of blood non-specific immune parameters in Bovine virus diarrhoea
      virus (BVDV) persistently infected and in immune heifers.
AB  - Several data from different authors show that Bovine virus diarrhoea virus (BVDV)
      could be a key component in multiple-etiology diseases, indeed a lower leukocytes
      number and their impaired functions decrease the resistance to infections.
      However, most of the information on the impairment of immune function during BVDV
      infections arise from circumstantial evidence and from experimental infection
      studies, and few from field data. To assess the effects of BVDV on blood cells
      parameters, cellular and humoral functions under field conditions, we designed a
      controlled study in commercial dairy herds, comparing persistent infected (PI)
      and healthy heifers. A total of 45 heifers were considered, the PI animals were
      nine, the control animals were 34, while two controls were considered as acute
      infected animals. The comparison of the mean values in PI calves showed a
      significant decrease for leukocytes and granulocytes, while platelets showed a
      significant increase, when compared with control animals. The total number of
      lymphocytes decreased not significantly in PI animals, while the proportion
      significantly increased. The number and proportion of monocytes was significantly
      reduced in PI animals, when compared with controls. The data collected on markers
      of cellular immunity during our study cannot be compared with the literature
      because there are no reference values. The presence of a persistent infection
      affected the cellular enzymes: NAGase, lysozyme and respiratory burst showed a
      large statistically significant decrease in PI animals when compared with
      controls. The presence of a persistent infection with BVD virus influenced blood
      cells number and impaired some blood cell functions. Such impairment confirms
      that PI animals represent a threat to the herd not only because they could spread
      BVDV, but also because they are more susceptible to other infectious diseases.

PMID- 16626402
TI  - Porcine reproductive and respiratory syndrome virus (PRRSV): a ring test
      performed in Germany to assess RT-PCR detection methods.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen
      of swine. Due to genetic variation between the European and the US genotype as
      well as within both genotypes detection of PRRSV is a diagnostic challenge. This
      paper reports on a ring test to compare different established reverse
      transcriptase polymerase chain reaction methods applied routinely in 16 different
      laboratories in Germany. Three different sets of samples were sent to the
      laboratories which were to be analysed as follows: (i) basis package: detection
      of PRRS (yes/no); (ii) differentiation package I: differentiation of EU and US
      genotypes; and (iii) differentiation package II: differentiation of EU field
      isolates and EU vaccine strain. A total of 80% of the samples of the basic
      package were analysed correctly, the analysis of the differentiation package I
      revealed 61.82% correctly tested samples and the two laboratories that analysed
      the differentiation package II showed only one correct result. The ring test
      showed that the majority of incorrect diagnoses were false-negative results.

PMID- 16626403
TI  - Detection of the astA (EAST1) gene in attaching and effacing Escherichia coli
      from ruminants.
AB  - A total of 206 attaching and effacing Escherichia coli strains from ruminants
      were analysed for the presence of the astA (EAST1) and bfpA genes. None of these
      strains was bfpA-positive. The percentage of enteropathogenic E. coli (EPEC)
      strains astA-positive found in healthy cattle (15.6%) suggests that this animal
      species may be a significant reservoir of atypical EPEC potentially pathogenic
      for humans.

PMID- 16626404
TI  - Seroprevalence of Anaplasma phagocytophilum among healthy dogs and horses in
      Israel.
AB  - The presence of reacting antibodies to Anaplasma phagocytophilum has previously
      been demonstrated in Israel, both in humans and the golden jackal (Canis aureus
      syriacus). This study was undertaken to determine the seroprevalence of A.
      phagocytophilum antibodies in two additional potential hosts, domestic dogs and
      horses in order to investigate the possibility of exposure to the organism in
      Israel. Of 195 dogs tested, 9% were seroreactive with A. phagocytophilum antigen
      and 30% were seroreactive to Ehrlichia canis. Twenty-nine percent of the dogs
      seropositive for E. canis were also reactive to A. phagocytophilum. Two dogs had
      immunofluorescence antibody (IFA) antibody titres for A. phagocytophilum greater
      than E. canis. The equine serological survey (n = 300) revealed no seroreactive
      horses. The results presented in this study suggest that dogs in Israel could
      have been accidentally exposed to A. phagocytophilum, for example by ticks
      carried on migrating birds, however, the possibility of cross-reaction with E.
      canis should also be considered. In spite of the high prevalence of ticks on
      horses in Israel during the summer months, no evidence for exposure to A.
      phagocytophilum was apparent.

PMID- 16626405
TI  - Normal somatic cell count and subclinical mastitis in Murrah buffaloes.
AB  - This study was conducted to investigate the normal somatic cell count (SCC) and
      to define subclinical mastitis in Murrah buffaloes. Data were collected from 60
      clinically normal buffaloes stationed at five farms of Chitwan Nepal and Buffalo
      Research Center, Hissar, India. Somatic cell count was measured using the Newman
      Lampert staining technique. The upper limit of SCC was determined >or=200 000/ml
      of milk based on the mean +/- 2SD of a total SCC. Abnormal data of the SCC was
      repeatedly removed, which lie beyond the values of more than mean + 2SD until all
      the data come to lie within (mean + 2SD). Averages of SCC of right front and
      right hind quarters were significantly higher than left front and left hind
      quarters. Nearly 94% of California mastitis test (CMT) negative quarters were
      having somatic cells >or=200 000/ml. The mean SCC of CMT positive quarter was
      significantly higher (P < 0.01) than CMT negative quarters. Subclinical mastitis
      was diagnosed on the basis of samples with SCCs >or=200 000/ml with positive
      bacterial cultures. Subclinical mastitis was found in 21.7% buffaloes and 8% of
      the quarter foremilk samples. Neutrophil counts were significantly higher in
      subclinical mastitis milk.

PMID- 16626406
TI  - Serodiagnostic comparison between two methods, ELISA and surface plasmon
      resonance for the detection of antibody titres of Mycoplasma hyopneumoniae.
AB  - A protein chip based on surface plasmon resonance (SPR) was developed for
      measuring the Mycoplasma hyopneumoniae antibody titres using a recombinant 30-kDa
      fragment of P97 adhesin as an antigen. The diagnostic potential of this SPR
      assay, for detecting the antibody titres to the M. hyopneumoniae 30-kDa protein,
      was compared with that of conventional ELISA using 70 pig serum samples taken
      from six pig farms. The SPR assay was found to be highly specific and sensitive.
      Moreover, there was a strong positive correlation between the SPR and ELISA
      titres (n = 70, r = 0.898, P < 0.01). Therefore, this recombinant 30-kDa protein
      can be used as an antigen for serological studies, and the SPR, which is a label
      free method, is expected to be a valuable and reproducible tool in the
      serodiagnosis of M. hyopneumoniae infection.

PMID- 16626407
TI  - Sero-epidemiology of canine leptospirosis in Trinidad: serovars, implications for
      vaccination and public health.
AB  - A sero-epidemiological study on canine leptospirosis was conducted in house,
      stray, farm and hunting dogs, as well as in suspect cases of clinical canine
      leptospirosis. Serum samples were collected from apparently healthy (vaccinated
      and non-vaccinated), house dogs. A questionnaire was administered to the owners
      to elicit information on risk factors for leptospirosis. The microscopic
      agglutination test was used to screen for leptospirosis using 17 international
      serovars. Reciprocal titres of between 100 and <800 were considered as evidence
      of past exposure while reciprocal titres of 800 or greater were classified as
      suggestive of acute/current infection. Of a total of 419 serum samples tested, 61
      (14.6%) were seropositive for Leptospira agglutinins, 23 (5.5%) had mixed
      infections and 16 (3.8%) had current infection. Amongst 50 suspected cases of
      clinical leptospirosis, 24 (48.0%) were seropositive and only 13 (26.0%) had
      current infection compared with 10 (6.3%) and three (1.9%) of 160 apparently
      healthy house dogs respectively. The difference was statistically significant (P
      < 0.05; chi2). Twelve (25.5%) of 47 hunting dogs, 10 (20.4%) of 49 farm dogs and
      five (4.4%) of 113 stray dogs were seropositive (P < 0.05; chi2). Overall, a
      total of nine serovars were detected with serovars mankarso, icterohaemorrhagiae
      RGA, autumnalis and copenhageni being involved in 29 (47.5%), 20 (32.8%), 25
      (41.0%) and 10 (16.4%) respectively in 61 seropositive dogs (P < 0.05; chi2).
      Serovar mankarso was most predominant in seropositive apparently healthy dogs,
      37.8% (14/37), suspected clinical cases of leptospirosis, 62.5% (15/24) compared
      with serovar icterohaemorrhagiae with a frequency of 21.6% (8/37) and 50.0%
      (12/24), the difference being statistically significant (P < 0.05; chi2).
      Although all vaccines used for prevention of canine leptospirosis in the country
      contain serovars canicola and icterohaemorrhagiae, serovar mankarso was mostly
      associated with infection and disease and may be a good candidate for inclusion
      in the vaccine used locally. The public health risk posed to owners of dogs
      infected with Leptospira cannot be over-emphasized considering the zoonotic
      nature of the disease.

PMID- 16626408
TI  - American foulbrood of the honey bee: occurrence and distribution of different
      genotypes of Paenibacillus larvae in the administrative district of Arnsberg
      (North Rhine-Westphalia).
AB  - Between March 2003 and October 2004, Paenibacillus larvae, the aetiological agent
      of American foulbrood disease of the honey bee, was isolated from broodcombs and
      honey samples of 54 apiaries in the administrative district of Arnsberg (North
      Rhine-Westphalia, Germany). Genotyping of 176 P. larvae isolates with repetitive
      element polymerase chain reaction fingerprinting (rep-PCR) using BOX A1R and MBO
      REP1 primers revealed five different genotypes (AB, Ab, ab, ass, Acapital BE,
      Cyrillic). In samples of three apiaries, more than one genotype was detected. A
      combination of two genotypes was isolated from honey samples of the same hive two
      times (ab/ass and Ab/ab). The five genotypes were not randomly distributed in the
      district, but revealed a certain geographical clustering. Possible factors with
      impact on the genotype diversity and the distribution pattern are discussed.

PMID- 16626409
TI  - Determinants of health economic decisions in actual practice: the role of
      behavioral economics. Summary of the presentation given by Professor Daniel
      Kahneman at the ISPOR 10th Annual International Meeting First Plenary Session,
      May 16, 2005, Washington, DC, USA.

PMID- 16626410
TI  - Cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis
      against venous thromboembolism in patients undergoing hip fracture surgery.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of fondaparinux relative to
      enoxaparin as prophylaxis against venous thromboembolism (VTE) in patients
      undergoing hip fracture surgery. METHODS: A decision analysis model was created
      to simulate the impact of fondaparinux 2.5 mg once daily relative to enoxaparin
      30 mg twice daily on patient outcomes and costs over various time points up to 5
      years after surgery. Probabilities for the analysis were estimated for a
      hypothetical cohort of 1000 patients undergoing hip fracture surgery in the
      United States receiving either fondaparinux or enoxaparin according to
      comparative trial results. Resource use and costs (2003 dollars) were obtained
      from large health-care databases. Outcome measures were rates of symptomatic VTE
      events, health-care costs, and incremental cost-effectiveness ratios. RESULTS:
      Fondaparinux is estimated to prevent an additional 30 VTE events (per 1000
      patients) at 3 months compared with enoxaparin, producing savings of 103 dollars
      at discharge, 290 dollars over 1 month, 361 dollars over 3 months, and 466
      dollars over 5 years. The results remain robust to clinically plausible variation
      in input parameters and assumptions. CONCLUSIONS: Fondaparinux improves outcomes
      and is cost-saving over a broad range of assumptions compared with enoxaparin for
      prophylaxis of VTE after hip fracture surgery.

PMID- 16626411
TI  - Cost-effectiveness of olanzapine as first-line treatment for schizophrenia:
      results from a randomized, open-label, 1-year trial.
AB  - OBJECTIVES: This randomized, open-label trial was designed to help inform
      antipsychotic treatment policies. It compared the 1-year cost-effectiveness of
      initial treatment with olanzapine (OLZ) (n = 229) versus a "fail-first" algorithm
      on conventional antipsychotics (then olanzapine if indicated) (CON) (n = 214);
      and versus initial treatment with risperidone (RIS) (n = 221). METHODS:
      Individuals with schizophrenia or schizoaffective disorder were recruited from
      May 1998 to September 2001. Clinical, functioning, and resource utilization data
      were collected at baseline and five postbaseline visits. Brief Psychiatric Rating
      Scale scores defined "clinical effectiveness;" Lehman Quality of Life Scale
      social relations scores defined "social effectiveness." RESULTS: Requiring
      failure on less expensive antipsychotics before use of olanzapine did not result
      in total cost savings, despite significantly higher antipsychotic costs with OLZ.
      Total 1-year mean costs were 21,283 dollars for CON; 20,891 dollars for OLZ; and
      21,347 dollars for RIS (pair-wise comparisons nonsignificant). Intent-to-treat
      effectiveness comparisons (nonsignificant) were augmented by analyses that
      adjusted for duration on initial antipsychotic treatment, and by comparisons of
      patients remaining on initial antipsychotic treatment versus those who required
      switching. When accounting for differential switching rates (OLZ 0.14 vs. CON
      0.53, P < 0.0001; vs. RIS 0.31, P < 0.0001), OLZ was significantly more effective
      than CON on clinical (P = 0.025) and social (P = 0.043) measures, and
      significantly more effective than RIS on the social (P = 0.002) measure. Further,
      patients initiated on an antipsychotic from which they needed to switch required
      additional resources for hospitalization (P = 0.036) and crisis services (P =
      0.029). CONCLUSIONS: Approaches that integrate costs, effectiveness, and
      treatment patterns are important for providing optimal information regarding the
      value of first-line antipsychotic options for schizophrenia.

PMID- 16626412
TI  - Performance of the EQ-5D in patients with irritable bowel syndrome.
AB  - OBJECTIVE: The EQ-5D is a standardized, nondisease-specific instrument for
      evaluating patients' preference-based valuations of health-related quality of
      life (HRQoL). This study's purpose was to determine the psychometric properties
      of EQ-5D in patients with irritable bowel syndrome (IBS). METHODS: Data from four
      European IBS studies were assessed: UK (n = 161 and n = 297), Spain (n = 503),
      and Germany (n = 100). The EQ-5D is a five-item health state descriptive system
      used to develop health states (EQ-5D(INDEX)) and a visual analog scale (VAS) (0
      100 from worst to best imaginable health state, EQ-5D(VAS)). Measures used with
      the EQ-5D included the SF-36, Irritable Bowel Syndrome--Quality of Life (IBS
      QOL), and both subjective and clinical global assessments of IBS. Convergent
      validity was assessed using SF-36 and IBS-QOL data, discriminant validity using
      global ratings of IBS severity, and responsiveness by subjective and physician
      assessment of condition. RESULTS: Moderate-to-high associations (r >or= 0.33)
      were seen between the EQ-5D(VAS) and the SF-36 and IBS-QOL subscales. Mean
      response scores to EQ-5D(INDEX) dimensions and the EQ-5D(VAS) score were
      significantly better for control patients than for patients with IBS (all P <
      0.01). The EQ-5D(VAS) was able to discriminate between levels of pain severity
      (quartiles, P < 0.001; mild/moderate/severe, P < 0.05) and general health
      severity (mild/moderate/severe, P < 0.001). The EQ-5D(VAS) and the EQ-5D(INDEX)
      were responsive in patients using both a self-perceived (Subject's Global
      Assessment) and physician-rated (Clinic Global Assessment) improvement.
      CONCLUSIONS: The EQ-5D performs well in comparison to general and disease
      specific outcomes. It is a valid and responsive measure that can be used to
      generate preference-based valuations of HRQoL in patients with IBS and useful for
      comparisons in clinical and cost-effectiveness studies.

PMID- 16626413
TI  - Validation of electronic data capture of the Irritable Bowel Syndrome--Quality of
      Life Measure, the Work Productivity and Activity Impairment Questionnaire for
      Irritable Bowel Syndrome and the EuroQol.
AB  - OBJECTIVES: To assess the comparability, reliability, and subject acceptability
      of electronic data capture (EDC) versions of Irritable Bowel Syndrome-Quality of
      Life (IBS-QOL), EuroQoL (EQ-5D) and Work Productivity and Activity Impairment
      (WPAI:IBS) instruments. METHODS: Comparability of EDC and paper questionnaires
      was evaluated in 72 subjects with IBS who completed a baseline EDC or paper
      questionnaire, a crossover questionnaire 24 hours later, and a retest of the
      crossover version at 1 week. The EDC version was presented on a hand-held device.
      Comparability was assessed using paired t-test statistics, intraclass correlation
      coefficients (ICC) and tests for internal consistency (Cronbach's alpha).
      RESULTS: No significant differences were found between scores obtained by paper
      questionnaire and EDC at the baseline and crossover assessments. ICCs between
      baseline and crossover assessments ranged from 0.83 to 0.96 for the IBS-QOL
      scores, 0.82 to 0.96 for the WPAI:IBS scores, and 0.77 to 0.82 for the EQ-5D.
      Internal consistency was comparable for the two data collection methods for the
      IBS-QOL overall score (0.96) and subscales and the EQ-5D Index (0.70 vs. 0.74).
      Retest statistics (ICC) were generally comparable between the EDC and paper
      versions for all scores. Ease of use was comparable for the two modes of
      administration, but more patients preferred EDC (47.2%) than the paper
      questionnaire (23.6%). CONCLUSIONS: EDC versions of the IBS-QOL, EQ-5D, and
      WPAI:IBS are comparable to paper questionnaires in internal consistency and test
      retest reliability, and have greater patient acceptability.

PMID- 16626414
TI  - A primer on dynamic optimization and optimal control in pharmacoeconomics.
AB  - Pharmacoeconomic analyses employ a wide range of techniques and methods to help
      societies allocate scarce health-care resources wisely, fairly, and efficiently.
      Techniques such as dynamic optimization and optimal control, however, have yet to
      be exploited by this field. Although control theory has a long history in
      mathematical biology and disease management, its application to economic costs in
      these disciplines has not yet been explored. Pharmacoeconomics therefore may
      offer a particularly promising starting point because of the emphasis this field
      places on the economic perspective. Although challenges may exist to implementing
      these techniques in practice (at least in some settings), there will nevertheless
      be value to considering the dynamic perspective these techniques offer, which
      requires thinking more critically about the optimal allocation of scare health
      care resources over time. Therefore, our article serves as a primer to introduce
      this dynamic perspective from an economic standpoint within the context of two
      examples of treating of hyperlipidemia.

PMID- 16626415
TI  - The instrumental variable method to study self-selection mechanism: a case of
      influenza vaccination.
AB  - OBJECTIVE: To assess whether estimates of the effectiveness of influenza
      vaccination in reducing rates of hospitalizations and all-cause mortality derived
      from cross-sectional data could be improved by applying the instrumental variable
      (IV) method to data representing the community-dwelling elderly population in the
      United States in order to adjust for self-selection bias. METHODS: Secondary data
      analysis, using the 1996-97 Medicare Current Beneficiary Survey data. First,
      using single-equation probit regressions this study analyzed influenza-related
      hospitalization and death due to all causes predicted by vaccination status,
      which was measured by claims or survey data. Second, to adjust for potential self
      selection of the vaccine receipt, for example, higher vaccination rates among
      high-risk individuals, bivariate probit (BVP) models and two-stage least squares
      (2SLS) models were employed. The IV was having either arthritis or gout. RESULTS:
      In single-equation probit models, vaccination appeared to be ineffective or even
      to increase the probability of adverse outcomes. Based on BVP and 2SLS models,
      vaccination was demonstrated to be effective in reducing influenza-related
      hospitalization by at least 31%. The BVP model results implied significant self
      selection in the single-equation probit models. CONCLUSIONS: Adjusting for self
      selection, BVP analyses yielded vaccine effectiveness estimates for a nationally
      representative cross-sectional sample of the community-dwelling elderly
      population that are consistent with previous estimates based on randomized
      controlled trials, prospective cohort studies, and meta-analyses. This result
      suggests that analyses with 2SLS and BVP in particular may be useful for the
      analysis of observational data regarding prevention in which self-selection is an
      important potential source of bias.

PMID- 16626416
TI  - Incorporating direct and indirect evidence using bayesian methods: an applied
      case study in ovarian cancer.
AB  - OBJECTIVE: To demonstrate the application of a Bayesian mixed treatment
      comparison (MTC) model to synthesize data from clinical trials to inform
      decisions based on all relevant evidence. METHODS: The value of an MTC model is
      demonstrated using a probabilistic decision-analytic model developed to assess
      the cost-effectiveness of second-line chemotherapy in ovarian cancer. Three
      clinical trials were found that each made a different pair-wise comparison of
      three treatments of interest in the overall patient population. As no common
      comparator existed between the three trials, an MTC model was used to assess the
      combined weight of evidence on survival from all three trials simultaneously.
      This analysis was compared to an alternative approach that combined two of the
      trials to make the same comparison of all three treatments using a common
      comparator, and an informal approach that did not synthesize the available
      evidence. RESULTS: By including all three trials using an MTC model, the credible
      intervals around estimated overall survival were reduced compared with making the
      same comparison using only two trials and a common comparator. Nevertheless, the
      survival estimates from the MTC model result in greater uncertainty around the
      optimal treatment strategy at a cost-effectiveness threshold of 30,000 pounds per
      quality-adjusted life-year. CONCLUSIONS: MTC models can be used to combine more
      data than would typically be included in a traditional meta-analysis that relies
      on a common comparator. They can formally quantify the combined uncertainty from
      all available evidence, and can be conducted using the same analytical approaches
      as standard meta-analyses.

PMID- 16626417
TI  - Psychometric evaluation of a new questionnaire measuring treatment satisfaction
      in hypothyroidism: the ThyTSQ.
AB  - OBJECTIVES: There is a clinical impression of dissatisfaction with treatment for
      hypothyroidism among some patients. Psychometric properties of the new ThyTSQ
      questionnaire are evaluated. The questionnaire, measuring patients' satisfaction
      with their treatment for hypothyroidism, has two parts: the seven-item ThyTSQ
      Present and four-item ThyTSQ-Past, measuring satisfaction with present and past
      treatment, respectively, on scales from 6 (very satisfied) to 0 (very
      dissatisfied). METHODS: The questionnaire was completed once by 103 adults with
      hypothyroidism, age (mean [SD]) 55.2 [14.4], range 23-84 years (all treated with
      thyroxine). RESULTS: Completion rates were very high. Internal consistency
      reliability was excellent for both ThyTSQ-Present and ThyTSQ-Past (Cronbach's
      alpha = 0.91 and 0.90, respectively [N = 102 and 103]). Principal components
      analyses indicated that the seven items of the ThyTSQ-Present and the four items
      of the ThyTSQ-Past could be summed into separate Present Satisfaction and Past
      Satisfaction total scores. Mean Present Satisfaction was 32.5 (7.8), maximum
      range 0-42, and mean Past Satisfaction was 17.5 (6.1), maximum range 0-24,
      indicating considerable room for improvement. Patients were least satisfied with
      their present understanding of their condition, mean 4.2 (1.7) (maximum range 0
      6), and with information provided about hypothyroidism around the time of
      diagnosis, mean 3.9 (1.8) (maximum range 0-6). CONCLUSIONS: The ThyTSQ is highly
      acceptable to patients with hypothyroidism (excellent completion rates), and has
      established internal consistency reliability. It will assist health professionals
      in considering psychological outcomes when treating people with hypothyroidism,
      and is suitable for clinical trials and routine clinical monitoring.

PMID- 16626419
TI  - Giant cell arteritis.

PMID- 16626420
TI  - Cornea, intraocular pressure and glaucoma.

PMID- 16626421
TI  - Pars plana insertion of glaucoma drainage devices for refractory glaucoma.
AB  - BACKGROUND: Glaucoma drainage devices are more commonly inserted into the
      anterior chamber because of the relative ease of this method of insertion.
      However, in certain cases, posterior placement of the tube may be necessary or
      may be more desirable. The outcome of a series of patients with glaucoma drainage
      devices inserted into the pars plana was examined. METHODS: Retrospective chart
      review of patients who underwent pars plana implantation of Molteno and Baerveldt
      glaucoma drainage devices at the Sydney Eye Hospital. RESULTS: There were 33
      cases reviewed. The mean follow-up period was 30.2 months. The mean final
      postoperative intraocular pressure was reduced to 13.4 +/- 4.4 mmHg (SD) from
      33.06 +/- 8.47 mmHg preoperatively. The mean number of intraocular pressure
      lowering medications in use postoperatively was 0.6 +/- 0.8, reduced from 3.6 +/-
      1.27 medications in use preoperatively. Sixteen (48.5%) eyes were classified as
      complete successes, 14 (42.4%) eyes as qualified successes and three eyes (9%) as
      failures. Kaplan-Meier survival analysis for cumulative success (absence of
      failure) predicted 61.1% survival at 60 months. Complications included five cases
      of decompensation of corneas or corneal grafts, one case each of conjunctival
      wound dehiscence, large choroidal effusion, epiretinal membrane, Molteno plate
      extrusion and intraocular pressure unresponsive to medical therapy, and three
      cases of tube blockage. CONCLUSIONS: In this series of patients, pars plana
      insertion of glaucoma drainage devices has been shown to be an effective
      alternative for selected cases where anterior chamber tube insertion is not
      possible or is not ideal.

PMID- 16626422
TI  - Conjunctival impression cytology in pseudoexfoliative glaucoma and
      pseudoexfoliation syndrome.
AB  - BACKGROUND: In this study, ocular surface changes and tear film functions in
      patients with pseudoexfoliative glaucoma (PEXG) and pseudoexfoliation (PEX)
      syndrome were evaluated. METHODS: This study is a randomized, double-blind and
      prospective study. Conjunctival impression cytology, tear film break-up time
      (TFBUT) test and basal Schirmer test (BST) were performed on 45 eyes of 45
      subjects with PEXG (group I), 48 eyes of 48 subjects with PEX syndrome (group 2)
      and 50 eyes of 50 normal subjects (group 3). Impression cytology was graded 0-III
      based on the shape, eosinophilic-staining cytoplasm and nucleocytoplasmic ratio
      of the epithelial cells, and the shape, quantity and Periodic Acid Schiff
      positive cytoplasm of the goblet cells. RESULTS: Impression cytology grading
      scores were 6.7% grade 0, 15.6% grade I, 37.7% grade II and 40% grade III in
      group 1, 6.3%, 18.7%, 43.8% and 31.2% in group 2 and 38%, 36.0%, 20% and 6% in
      group 3, respectively. The scores in groups 1 and 2 were significantly higher
      than in group 3 (P = 0.001, chi(2) = 39.84). The mean values of TFBUT of groups
      1, 2 and 3 were 5.91 +/- 3.27, 7.39 +/- 4.82, 10.96 +/- 3.81 s and the mean
      values of BST were 7.82 +/- 3.56, 9.04 +/- 4.60 and 12.50 +/- 5.25 mm/5 min,
      respectively. The values of TFBUT and BST were lower in groups 1 and 2 than in
      group 3 (P = 0.001). CONCLUSION: The conjunctival changes in PEX and PEXG
      patients recorded in this study may explain the existence of tear film
      abnormalities in these patients. It has been shown that PEXG and PEX syndrome
      cause conjunctival surface changes and reduction of tear film functions.

PMID- 16626423
TI  - Diurnal variation of ocular hysteresis in normal subjects: relevance in clinical
      context.
AB  - BACKGROUND: This study was conducted to assess the diurnal variation in ocular
      hysteresis, as measured by the Ocular Response Analyser to establish a
      relationship between diurnal hysteresis variation and diurnal intraocular
      pressure (IOP) variation. METHODS: Forty-two normal eyes of 21 colleagues and
      staff in a teaching hospital in Birmingham, UK, were recruited. The IOP and
      hysteresis were measured by the Ocular Response Analyser. The central corneal
      thickness (CCT) was measured using a hand-held ultrasonic pachymeter in the mid
      pupillary axis. RESULTS: The mean ocular hysteresis at 8 am was 12.7 +/- 2.3
      mmHg, at 11 am was 12.2 +/- 2.0 mmHg, at 2 PM was 12.7 +/- 2.1 mmHg and at 5 PM
      was 12.7 +/- 1.7 mmHg; the difference between the values at any time of
      measurement was not statistically significant (P > 0.9, repeated measures). IOP
      as measured by non-contact tonometry was 18.4 +/- 2.8 mmHg, 17.9 +/- 3.3 mmHg,
      16.9 +/- 3.1 mmHg and 16.8 +/- 3.2 mmHg, respectively, for the same time period;
      the difference between the values in the morning and afternoon was statistically
      significant (P < 0.0001, repeated measures). The CCT was 548.8 +/- 29.5 microm,
      547.0 +/- 31.4 microm, 548.2 +/- 29.6 microm and 548.6 +/- 29.4 microm,
      respectively; the difference between the values was not statistically significant
      at any time points. Multiple regression analysis showed the relationship between
      IOP and hysteresis was not statistically significant (P = 0.9). CONCLUSION: The
      ocular hysteresis reading was almost constant throughout the day, whereas the IOP
      readings showed highest values in the morning with a reducing trend being lowest
      in the afternoon. The CCT values were almost stable throughout the day. IOP
      appears to vary independently of a variation in hysteresis or CCT.

PMID- 16626424
TI  - Semi-automated detection of the foveal avascular zone in fluorescein angiograms
      in diabetes mellitus.
AB  - BACKGROUND: The foveal avascular zone (FAZ) is known to enlarge in diabetic
      retinopathy. In a preliminary study, the authors applied a region growing
      algorithm to fluorescein angiograms to detect the FAZ in a semi-automated
      fashion. METHODS: The FAZ in 44 fluorescein angiograms of 44 eyes of 41 patients
      with diabetic retinopathy underwent manual outlining, then analysis with the
      region growing function of the ENVI image analysis software. The same algorithm
      was applied after median filtering of the images. RESULTS: Correlation
      coefficient was 0.98 between the first two authors, 0.89 between the first author
      and semi-automated detection before median filtering and 0.91 after median
      filtering. Average surface areas however, were smaller with semi-automated
      detection (1951 pixels before and 2226 pixels after median filtering) than with
      manual detection (3032 pixels). CONCLUSIONS: Semi-automated detection of the FAZ
      is possible, but refinements need to be made in angiogram quality and/or image
      pretreatment to improve results.

PMID- 16626425
TI  - Correlations between optical coherence tomography measurement of macular
      thickness and visual acuity after cataract extraction.
AB  - PURPOSE: To investigate correlations between optical coherence tomography macular
      thickness measurements and visual acuity after cataract surgery. METHODS: Sixty
      two patients underwent routine cataract surgery as part of a randomized clinical
      trial of oral Cox-2 inhibitor prophylaxis of cystoid macular oedema. Optical
      coherence tomography was used to quantify several parameters of macular
      thickness. Optical coherence tomography measurements were obtained before
      surgery, day one, week two and week six after surgery. These measurements were
      then correlated with logMAR best-corrected visual acuity. RESULTS: Optical
      coherence tomography macular thickness parameters increased after surgery by up
      to 20%. A significant correlation was identified between foveal minimum macular
      thickness and best-corrected visual acuity at day one and week six after surgery.
      Other macular parameters failed to show any significant correlation. At day one
      and week six, the 10 patients with greatest macular thickness had significantly
      lower visual acuity than the other patients. CONCLUSION: In this study routine
      cataract surgery caused an increase in macular thickness. Some significant
      positive correlations between macular thickness and best-corrected visual acuity
      were found, although not for all parameters or time points. There may be a
      threshold relationship between degree of foveal anatomic change and significant
      loss of visual acuity.

PMID- 16626426
TI  - Retinal nerve fibre layer thickness measurements in patients using chloroquine.
AB  - PURPOSE: Previous investigations have suggested that initial retinal damage from
      chloroquine toxicity occurs in ganglion cells, and other ocular tissues are
      affected only later on. The aim of this study was to evaluate retinal nerve fibre
      layer (RNFL) thickness measurements, as assessed by scanning laser polarimetry,
      in a group of patients under long-term treatment with chloroquine. METHODS: This
      case-control study included 34 patients using chloroquine diphosphate and 34 age
      matched healthy subjects with no previous history of chloroquine intake. All
      subjects underwent RNFL assessment using the GDx -- Nerve Fibre Analyser
      (software v.2.0.01). One eye of each patient was randomly selected for
      statistical analysis. Peripapillary RNFL measurements were compared between the
      two groups. For patients using chloroquine, the correlation between RNFL
      measurements and chloroquine dosage was assessed. RESULTS: Mean +/- SD RNFL
      thickness for patients using chloroquine was 60.6 +/- 11.2 microm, 65.6 +/- 13.2
      microm, 74.8 +/- 14.8 microm, 36.2 +/- 9.6 microm and 43.8 +/- 7.9 microm for
      global, superior, inferior, temporal and nasal regions, respectively. In the
      control group, the corresponding values were 72.1 +/- 12.7 microm, 79.9 +/- 14.8
      microm, 88.3 +/- 14.0 microm, 44.2 +/- 12.8 microm and 49.7 +/- 11.9 microm. Mean
      RNFL thickness measurements from patients using chloroquine were significantly
      different from those in the control group in all regions (P < 0.05). Thinner RNFL
      thickness measurements were associated with higher daily dosages of chloroquine.
      CONCLUSION: Patients under long-term chloroquine treatment had significantly
      lower RNFL thickness measurements than healthy subjects, and the RNFL loss was
      correlated to chloroquine daily dosage.

PMID- 16626427
TI  - Optical coherence tomographic pattern of fluorescein angiographic leakage site in
      acute central serous chorioretinopathy.
AB  - PURPOSE: To study the optical coherence tomography (OCT) pattern of the
      fluorescein angiographic leakage in acute central serous chorioretinopathy
      (CSCR). METHODS: This is a non-interventional pilot case study. OCT line scan was
      performed over the fluorescein angiographic leak site in eyes clinically
      diagnosed acute CSCR. Clinical fundus photograph, site of leakage on fundus
      fluorescein angiography and corresponding OCT were analysed. RESULTS: The mean
      age of 10 consecutive patients was 38.8 +/- 6.9 years. Six patients were male and
      the mean duration of symptom was 7 days. Six eyes (60%) showed a characteristic
      dipping pattern of neurosensory retina with intervening hyper-reflective echoes
      suggestive of fibrin over the leakage site. All these eyes had ink-blot leak and
      subretinal fibrin. CONCLUSIONS: Ink-blot leak in acute CSCR with subretinal
      fibrin generates a dipping morphological pattern on OCT.

PMID- 16626428
TI  - Eye care service utilization in older people seeking aged care.
AB  - BACKGROUND: To assess the need for, and the use of eye care services in older
      people seeking aged care. METHODS: In total, 188 people (69.1% of those eligible)
      aged 65+ years who were assessed for aged care provision at Westmead Hospital,
      Sydney, were recruited in 2003 and re-examined a year later. At baseline,
      presenting visual acuity (VA) was randomly assessed in half the participants.
      People with under-corrected refractive error (pinhole VA improved at least 10
      letters in those with presenting VA <6/6), bilateral visual impairment (better
      eye VA <6/12), or self-reported visual problems, were recommended to have further
      assessment by eye care professionals. At follow up, information on utilization of
      eye care services in the past 12 months was collected and VA was assessed in all
      returned participants. RESULTS: Of the 188 baseline participants, 121 (70% of
      survivors) were revisited a year later. Overall, 90/121 participants (74%) had
      seen an eye care professional in the previous year. Of the 66 participants who
      were recommended to see an eye care professional, 42 (64%) were revisited and
      37/42 (88%) complied with the recommendation. At revisit, bilateral visual
      impairment was found in 49/120 (41%). The proportion with bilateral visual
      impairment was lower in participants whose vision was assessed at baseline (35%)
      than in those whose vision was not assessed (47%, P = 0.17), and also lower among
      people who had visited an eye care professional during the previous 12 months
      (39%) than those who had not (45%, P = 0.57). CONCLUSIONS: This pilot study
      indicates a relatively high need for, and high utilization of eye care services
      in the subgroup of older people seeking aged care services.

PMID- 16626429
TI  - Causes of blindness among hospital outpatients in Ecuador.
AB  - BACKGROUND: There is a lack of published information on the causes of blindness
      in Ecuador and the Latin American region in general. This study is designed to
      enumerate the proportions of ocular conditions contributing to blindness in an
      outpatient population of an ophthalmology hospital in the coastal region of
      Ecuador. METHODS: All cases presenting to an ophthalmology outpatient clinic over
      a 3-week period during September 2004 were reviewed (n = 802). Visual acuity was
      measured using a Snellen acuity chart and those who met the criteria for
      blindness were included in the study (n = 118). Blindness was defined under the
      World Health Organization protocol as visual acuity of <3/60. Both unilateral and
      bilateral blindness were included in the study. The diagnosis of ocular pathology
      contributing to blindness was recorded. RESULTS: Among those considered to have
      unilateral blindness (n = 88), cataract was the most common cause (43%). This was
      followed by corneal pathologies (17%) and glaucoma (15%). Among those considered
      to have bilateral blindness (n = 30), refraction was the most common cause (37%),
      followed by cataract (23%) and glaucoma (17%). CONCLUSION: The major causes of
      blindness found in this study reflected those in estimated data for the region.
      More studies are needed to improve the quality and quantity of epidemiological
      data on blindness in Ecuador and Latin America. Many obstacles to successful
      implementation of prevention of blindness programmes in South America still need
      to be overcome.

PMID- 16626430
TI  - Old habits tie hard: an in vitro comparison of first-throw tension holding in
      Polyglycolic acid (Dexon S) and Polyglactin 910 (Coated Vicryl).
AB  - PURPOSE: To compare the first-throw tension holding property of two braided
      absorbable sutures commonly used in oculoplastic surgery. METHODS: The study was
      an in vitro experimental model. 6/0 Polyglycolic acid (Dexon S) and 6/0
      Polyglactin 910 (Coated Vicryl) were compared using an experimental model to
      determine first-throw knot security. A polypropylene suture (Surgipro 2) was
      included as a benchmark to judge the apparatus by, ensuring that our experiment
      could be designed independently of the test suture materials. Increasing metric
      loads were applied to the first double throw of a surgical knot. Each suture was
      tested to the point of knot slipping and the critical tension recorded. All the
      sutures were kept wet during use. Three variations of the experiment were
      undertaken: experiment 1 -- two metal loops brought together by the test suture;
      experiment 2 -- two strips of tissue brought together by the test suture; and
      experiment 3 -- a knot tied over a metal bar coated in tissue. The tissue used
      was processed cross-linked porcine dermal collagen (Permacol). Each experiment
      was repeated three times for each suture type and the mean value taken. RESULTS:
      Experiment 1: Dexon S 12.2 g (11, 12, 13.5), Coated Vicryl 2.5 g (2.5, 2.5, 2.5)
      and Surgipro 2 2.3 g (2, 2, 3); experiment 2: Dexon S 33.33 g (30, 35, 35),
      Coated Vicryl 25 g (25, 25, 25) and Surgipro 2 5 g (5, 5, 5); experiment 3: Dexon
      S 100 g (100, 100, 100), Coated Vicryl 56.667 g (60, 55, 55) and Surgipro 2 5 g
      (5, 5, 5). CONCLUSIONS: Dexon S-braided absorbable suture has significantly
      better first-throw knot security when compared with Coated Vicryl. This is an
      important property when suturing tissues under tension as it minimizes slippage
      before the locking throw is tied.

PMID- 16626431
TI  - Presymptomatic diagnosis of bronchogenic carcinoma associated with bilateral
      diffuse uveal melanocytic proliferation.
AB  - A 62-year-old man presented with bilateral diffuse uveal melanocytic
      proliferations (BDUMP) and painful flexor contractures of the fingers of both
      hands. All these features were considered paraneoplastic but extensive and
      repeated investigations revealed no underlying malignancy. Oral steroids and
      orbital radiotherapy were ineffective. The diagnosis was confirmed by trans
      scleral biopsy of the right choroid. Rapidly progressive cataracts were treated
      by phacoemulsification. Severe exudative retinal detachment with rubeosis and
      neovascular glaucoma in the left eye were treated successfully by partial
      choroidectomy. Fifteen months after presentation, investigations detected a 22
      mm, poorly differentiated adenocarcinoma, which was resected without
      complication. The ocular tumours in both eyes regressed, without improvement in
      vision of Light Perception, and the palmar fasciitis also improved. The patient
      remained free of tumour recurrence until sudden death from myocardial infarction
      five years after he first presented.

PMID- 16626432
TI  - Giant cell arteritis.
AB  - Giant cell arteritis (GCA) is an immune-mediated vasculitis, affecting medium- to
      large-sized arteries, in individuals over the age of 50 years. Visual loss is a
      frequent complication of GCA, and once it occurs it tends to be both permanent
      and profound. Although major advances have been made in recent years in genetics,
      molecular biology and the description of the vessel wall morphology, the
      aetiology and pathogenesis of GCA are still incompletely understood. Over the
      years there has been much debate over whether polymyalgia rheumatica and GCA are
      separate or linked entities. Recent investigations support that polymyalgia
      rheumatica and GCA are two different expressions of the same underlying
      vasculitic disorder. A single cause or aetiological agent has not as yet been
      identified. Except for the histopathology of the arterial wall, there are no
      laboratory findings specific for GCA, and no particular signs or symptoms
      specific for the diagnosis. GCA typically causes vasculitis of the extracranial
      branches of the aorta and spares intracranial vessels. Transmural inflammation of
      the arteries induces luminal occlusion through intimal hyperplasia. Clinical
      symptoms reflect end-organ ischaemia. Branches of the external and internal
      carotid arteries are particularly susceptible. Corticosteroids remain the only
      proven treatment for GCA, the regimen initially involving high doses followed by
      a slow taper. However, early detection and treatment with high-dose
      corticosteroids is effective in preventing visual deterioration in most patients.

PMID- 16626437
TI  - Vitreous and subretinal haemorrhage: an unusual complication of retinal racemose
      haemangioma.
AB  - Racemose haemangioma of the retina is a rare, usually unilateral developmental
      abnormality: an arteriovenous communication with variable alterations in
      capillary and arteriolar networks. Herein a case of a 57-year-old man with a
      vitreous and subretinal haemorrhage in the left eye is described.

PMID- 16626438
TI  - Spontaneous suprachoroidal hemorrhage secondary to thrombolysis for the treatment
      of myocardial infarction.
AB  - Suprachoroidal haemorrhage occurs most commonly as an intraoperative or a
      postoperative complication of ocular surgery. Spontaneous suprachoroidal
      haemorrhage is rare. Herein a case is described of spontaneous suprachoroidal
      haemorrhage in a patient who received recombinant tissue plasminogen activator
      for the treatment of a myocardial infarction. Systemic thrombolysis may induce
      spontaneous suprachoroidal haemorrhage. Prompt diagnosis and treatment can
      improve the likelihood of a favourable visual outcome. To the authors' knowledge,
      there have been only three previous reports in the literature of spontaneous
      suprachoroidal haemorrhage secondary to thrombolysis.

PMID- 16626439
TI  - Topical therapy with imiquimod for eyelid lesion.
AB  - Herein a case of clinically diagnosed lower eyelid lesion treated with topical
      imiquimod is reported. Macroscopic resolution of the lesion occurred 4 weeks
      after treatment with good cosmetic result. This is the first reported successful
      case of using this drug in treating eyelid lesion involving the lid margin.

PMID- 16626440
TI  - Decompression retinopathy and corneal oedema following Nd:YAG laser peripheral
      iridotomy.
AB  - Decompression retinopathy has been reported as a rare occurrence, subsequent to
      Nd:YAG laser peripheral iridotomy for the treatment of acute angle closure.
      Herein a case of a 67-year-old woman is described who developed decompression
      retinopathy in conjunction with unexpectedly severe corneal stromal oedema
      following Nd:YAG laser peripheral iridotomy for acute angle closure. The
      literature regarding these phenomena is reviewed.

PMID- 16626441
TI  - Retinopathy associated with photodynamic therapy for treatment of idiopathic
      choroidal neovascularization.
AB  - A case of retinopathy with retinal pigment epithelial alterations due to
      photodynamic therapy for the treatment of idiopathic choroidal neovascularization
      is reported. The possible mechanisms are discussed.

PMID- 16626442
TI  - Photodynamic therapy with Verteporfin for vascular leakage from a combined
      hamartoma of the retina and retinal pigment epithelium.
AB  - This interventional case report describes a patient with a combined hamartoma of
      the retina and retinal pigment epithelium (RPE), which was treated with
      photodynamic therapy (PDT) with Verteporfin. A 17-year-old girl presented with a
      combined hamartoma of the retina and RPE. Progressive decrease in vision due to
      vascular leakage and macular involvement led to the decision to treat this lesion
      with PDT. Rapid vascular closure occurred after PDT as confirmed by fundus
      fluorescein angiography and the clinical appearance gradually improved. However,
      visual acuity did not improve substantially. PDT with Verteporfin could be
      considered as a treatment modality for combined hamartomas of the retina and RPE,
      which demonstrate progressive vascular leakage.

PMID- 16626443
TI  - Orbital inflammation associated with Behcet's disease.
AB  - Herein a case of a 35-year-old woman with a history of Behcet's disease, who
      presented with swelling and redness of her right eye with increasing pain, is
      reported. Computed tomography and magnetic resonance imaging showed enlargement
      of the right lacrimal gland and contrast enhancement of the extraocular muscles.
      A diagnosis of orbital inflammation was made and the patient was treated with
      corticosteroids, with prompt resolution of symptoms and clinical signs. Orbital
      inflammation should be considered as an ophthalmic manifestation of Behcet's
      disease.

PMID- 16626444
TI  - Idiopathic orbital inflammation with sclerosing mesenteritis: a new association?
AB  - A 70-year-old man, who was recently diagnosed with sclerosing mesenteritis
      following an abdominal biopsy, presented with an acute onset of left upper eyelid
      swelling, moderate ptosis, mild chemosis and restriction of movements. A computed
      tomography scan showed an enlarged lateral rectus muscle with surrounding soft
      tissue changes. A diagnosis of orbital inflammation manifesting as myositis was
      made and the patient was commenced on high-dose prednisolone, which showed a
      rapid response. It is believed that this may be a new association similar to that
      previously reported with retroperitoneal fibrosis and orbital inflammation.

PMID- 16626445
TI  - Relative afferent pupillary defect, or afferent pupillary defect?

PMID- 16626447
TI  - Preface to the special issue: ecological and evolutionary genomics of populations
      in nature.

PMID- 16626448
TI  - Variation within and among species in gene expression: raw material for
      evolution.
AB  - Heritable variation in regulatory or coding regions is the raw material for
      evolutionary processes. The advent of microarrays has recently promoted
      examination of the extent of variation in gene expression within and among taxa
      and examination of the evolutionary processes affecting variation. This review
      examines these issues. We find: (i) microarray-based measures of gene expression
      are precise given appropriate experimental design; (ii) there is large inter
      individual variation, which is composed of a minor nongenetic component and a
      large heritable component; (iii) variation among populations and species appears
      to be affected primarily by neutral drift and stabilizing selection, and to a
      lesser degree by directional selection; and (iv) neutral evolutionary divergence
      in gene expression becomes nonlinear with greater divergence times due to
      functional constraint. Evolutionary analyses of gene expression reviewed here
      provide unique insights into partitioning of regulatory variation in nature.
      However, common limitations of these studies include the tendency to assume a
      linear relationship between expression divergence and species divergence, and
      failure to test explicit hypotheses that involve the ecological context of
      evolutionary divergence.

PMID- 16626449
TI  - Microarray analysis reveals differential gene expression in hybrid sunflower
      species.
AB  - This paper describes the creation of a cDNA microarray for annual sunflowers and
      its use to elucidate patterns of gene expression in Helianthus annuus, Helianthus
      petiolaris, and the homoploid hybrid species Helianthus deserticola. The array
      comprises 3743 ESTs (expressed sequence tags) representing approximately 2897
      unique genes. It has an average clone/EST identity rate of 91%, is applicable
      across species boundaries within the annual sunflowers, and shows patterns of
      gene expression that are highly reproducible according to real-time RT-PCR
      (reverse transcription-polymerase chain reaction) results. Overall, 12.8% of
      genes on the array showed statistically significant differential expression
      across the three species. Helianthus deserticola displayed transgressive, or
      extreme, expression for 58 genes, with roughly equal numbers exhibiting up- or
      down-regulation relative to both parental species. Transport-related proteins
      were strongly over-represented among the transgressively expressed genes, which
      makes functional sense given the extreme desert floor habitat of H. deserticola.
      The potential adaptive value of differential gene expression was evaluated for
      five genes in two populations of early generation (BC2) hybrids between the
      parental species grown in the H. deserticola habitat. One gene (a G protein
      coupled receptor) had a significant association with fitness and maps close to a
      QTL controlling traits that may be adaptive in the desert habitat.

PMID- 16626450
TI  - Expression profiling and local adaptation of Boechera holboellii populations for
      water use efficiency across a naturally occurring water stress gradient.
AB  - We studied the physiological basis of local adaptation to drought in Boechera
      holboellii, a perennial relative of Arabidopsis thaliana, and used cDNA-AFLPs to
      identify candidate genes showing differential expression in these populations. We
      compared two populations of B. holboellii from contrasting water environments in
      a reciprocal transplant experiment, as well as in a laboratory dry-down
      experiment. We continuously measured the water content of soils using time domain
      reflectometery (TDR). We compared populations for their water use efficiency
      (WUE), root/shoot ratios (R:S) and leaf mass per unit area (LMA) in the field and
      in the laboratory, and identified candidate genes that (i) responded plastically
      to water stress and (ii) were differentially expressed between the two
      populations. Genotypes from the drier site had higher WUE, which was attributable
      to a large reduction in transpirational water loss. The xeric-adapted population
      also had increased investment in root biomass and greater leaf mass per unit
      area. Reciprocal transplants in the field had significantly greater survival in
      their native habitat. In total, 450 cDNA-AFLP fragments showed significant
      changes between drought and control treatments. Furthermore, some genes showed
      genotype (population)-specific patterns of up- or down-regulation in response to
      drought. Three hundred cDNA-AFLP bands were sequenced leading to the
      identification of cDNAs coding for proteins involved in signal transduction,
      transcriptional regulation, redox regulation, oxidative stress and pathways
      involved in stress adaptation. Some of these proteins could contribute a
      physiological advantage under drought, making them potential targets for natural
      selection.

PMID- 16626451
TI  - Parallelism in gene transcription among sympatric lake whitefish (Coregonus
      clupeaformis Mitchill) ecotypes.
AB  - Abstract We tested the hypothesis that phenotypic parallelism between dwarf and
      normal whitefish ecotypes (Coregonus clupeaformis, Salmonidae) is accompanied by
      parallelism in gene transcription. The most striking phenotypic differences
      between these forms implied energetic metabolism and swimming activity.
      Therefore, we predicted that genes showing parallel expression should mainly
      belong to functional groups associated with these phenotypes. Transcriptome
      profiles were obtained from white muscle by using a 3557 cDNA gene microarray
      developed for the Atlantic salmon (Salmo salar). A total of 1181 genes expressed
      in both lake populations hybridized on the array. Significant differential
      expression between ecotypes was detected for 134 (11.3%) and 195 (16.5%) gene
      clones in Cliff Lake and Indian Pond, respectively. Fifty-one genes (4.3%) showed
      parallel differential expression between lakes, among which 35 were expressed in
      opposite directions. Sixteen genes (1.35%) showed true parallelism of
      transcription, which mainly belonged to energetic metabolism and regulation of
      muscle contraction functional groups. Variance in expression was significantly
      reduced for these genes compared to those not showing directionality in
      parallelism of expression. Candidate genes associated with parallelism in
      swimming activity and energetic metabolism based on their level and variance in
      expression were identified. These results add to the growing evidence that
      parallel phenotypic evolution also involves parallelism at both the genotypic and
      regulatory level, which may at least partly be associated with genetic
      constraints. It also provides further evidence for the determinant role of
      divergent natural selection in driving phenotypic divergence, and perhaps
      reproductive isolation, in the adaptive radiation of lake whitefish. This study
      adds to a nascent field employing microarrays as powerful tools for investigating
      the evolutionary processes of adaptive divergence among natural populations.

PMID- 16626452
TI  - Functional genomics of Buchnera and the ecology of aphid hosts.
AB  - In many animal groups, mutualistic bacterial symbionts play a central role in
      host ecology, by provisioning rare nutrients and thus enabling specialization on
      restricted diets. Among such symbionts, genomic studies are most advanced for
      Buchnera, the obligate symbiont of aphids, which feed on phloem sap. The contents
      of the highly reduced Buchnera genomes have verified its role in aphid nutrition.
      Comparisons of Buchnera gene sets indicate ongoing, irreversible gene losses that
      are expected to affect aphid nutritional needs. Furthermore, almost all
      regulatory genes have been eliminated, raising the question of whether and how
      gene expression responds to environmental change. Microarray studies on genome
      wide expression indicate that Buchnera has evolved some constitutive changes in
      gene expression: homologues of heat stress genes have elevated transcript levels
      in Buchnera (relative to other bacteria) even in the absence of stress.
      Additionally, the microarray results indicate that responses to heat stress and
      to amino acid availability are both few and modest. Observed responses are
      consistent with control by the few ancestral regulators retained in the genome.
      Initial studies on the role of host genes in mediating the symbiosis reveal
      distinctive expression patterns in host cells harbouring Buchnera. In the near
      future, a complete genome of pea aphid will accelerate progress in understanding
      the functional integration of aphid and Buchnera genomes. Although information
      for other insect symbioses is relatively limited, studies on symbionts of
      carpenter ants and tsetse flies indicate many similarities to Buchnera.

PMID- 16626453
TI  - A cDNA macroarray approach to parasite-induced gene expression changes in a
      songbird host: genetic response of house finches to experimental infection by
      Mycoplasma gallisepticum.
AB  - In 1994, the bacterial parasite Mycoplasma gallisepticum expanded its host range
      and swept through populations of a novel host--eastern US populations of the
      house finch (Carpodacus mexicanus). This epizootic caused a dramatic decline in
      finch population numbers, has been shown to have caused strong selection on house
      finch morphology, and presumably caused evolutionary change at the molecular
      level as finches evolved enhanced resistance. As a first step toward identifying
      finch genes that respond to infection by Mycoplasma and which may have
      experienced natural selection by this parasite, we used suppression subtractive
      hybridization (SSH) and cDNA macroarray approaches to identify differentially
      expressed genes regulated by the Mycoplasma parasite. Two subtractive cDNA
      libraries consisting of 16,512 clones were developed from spleen using an
      experimentally uninfected bird as the 'tester' and an infected bird as 'driver',
      and vice versa. Two hundred and twenty cDNA clones corresponding 34 genes with
      known vertebrate homologues and a large number of novel transcripts were found to
      be qualitatively up- or down-regulated genes by high-density filter
      hybridization. These gene expression changes were further confirmed by a high
      throughout reverse Northern blot approach and in specific cases by targeted
      Northern analysis. blast searches show that heat shock protein (HSP) 90, MHC II
      associated invariant chain (CD74), T-cell immunoglobulin mucin 1 (TIM1), as well
      as numerous novel expressed genes not found in the databases were up- or down
      regulated by the host in response to this parasite. Our results and macroarray
      resources provide a foundation for molecular co-evolutionary studies of the
      Mycoplasma parasite and its recently colonized avian host.

PMID- 16626454
TI  - Genomics of hybrid poplar (Populus trichocarpax deltoides) interacting with
      forest tent caterpillars (Malacosoma disstria): normalized and full-length cDNA
      libraries, expressed sequence tags, and a cDNA microarray for the study of insect
      induced defences in poplar.
AB  - As part of a genomics strategy to characterize inducible defences against insect
      herbivory in poplar, we developed a comprehensive suite of functional genomics
      resources including cDNA libraries, expressed sequence tags (ESTs) and a cDNA
      microarray platform. These resources are designed to complement the existing
      poplar genome sequence and poplar (Populus spp.) ESTs by focusing on herbivore-
      and elicitor-treated tissues and incorporating normalization methods to capture
      rare transcripts. From a set of 15 standard, normalized or full-length cDNA
      libraries, we generated 139,007 3'- or 5'-end sequenced ESTs, representing more
      than one-third of the c. 385,000 publicly available Populus ESTs. Clustering and
      assembly of 107,519 3'-end ESTs resulted in 14,451 contigs and 20,560 singletons,
      altogether representing 35,011 putative unique transcripts, or potentially more
      than three-quarters of the predicted c. 45,000 genes in the poplar genome. Using
      this EST resource, we developed a cDNA microarray containing 15,496 unique genes,
      which was utilized to monitor gene expression in poplar leaves in response to
      herbivory by forest tent caterpillars (Malacosoma disstria). After 24 h of
      feeding, 1191 genes were classified as up-regulated, compared to only 537 down
      regulated. Functional classification of this induced gene set revealed genes with
      roles in plant defence (e.g. endochitinases, Kunitz protease inhibitors),
      octadecanoid and ethylene signalling (e.g. lipoxygenase, allene oxide synthase, 1
      aminocyclopropane-1-carboxylate oxidase), transport (e.g. ABC proteins,
      calreticulin), secondary metabolism [e.g. polyphenol oxidase, isoflavone
      reductase, (-)-germacrene D synthase] and transcriptional regulation [e.g.
      leucine-rich repeat transmembrane kinase, several transcription factor classes
      (zinc finger C3H type, AP2/EREBP, WRKY, bHLH)]. This study provides the first
      genome-scale approach to characterize insect-induced defences in a woody
      perennial providing a solid platform for functional investigation of plant-insect
      interactions in poplar.

PMID- 16626455
TI  - A predicted microsatellite map of the passerine genome based on chicken-passerine
      sequence similarity.
AB  - Abstract We present a predicted passerine genome map consisting of 196
      microsatellite markers distributed across 25 chromosomes. The map was constructed
      by assigning chromosomal locations based on the sequence similarity between 550
      publicly available passerine microsatellites and the draft chicken genome
      sequence published by the International Chicken Genome Sequencing Consortium. We
      compared this passerine microsatellite map with a recently published great reed
      warbler (Acrocephalus arundinaceus) linkage map derived from the segregation of
      marker alleles in a pedigree of a natural population. Twenty-four microsatellite
      markers were shared between the two maps, distributed across ten chromosomes.
      Synteny was maintained between the predicted passerine microsatellite map and the
      great reed warbler linkage map, confirming the validity and accuracy of our
      approach. Possible applications of the predicted passerine microsatellite map
      include genome mapping; quantitative trait locus (QTL) discovery; understanding
      heterozygosity-fitness correlations; investigating avian karyotype evolution;
      understanding microsatellite mutation processes; and for identifying loci
      conserved in multiple species, unlinked loci for use in genotyping sets and sex
      linked markers.

PMID- 16626456
TI  - Identifying loci under selection across contrasting environments in Avena barbata
      using quantitative trait locus mapping.
AB  - We constructed recombinant inbred lines of a cross between naturally occurring
      ecotypes of Avena barbata (Pott ex Link), Poaceae, associated with contrasting
      moisture environments. These lines were assessed for fitness in common garden
      reciprocal transplant experiments in two contrasting field sites in each of two
      years, as well as a novel, benign greenhouse environment. An AFLP (amplified
      fragment length polymorphism) linkage map of 129 markers spanned 644 cM in 19
      linkage groups, which is smaller, with more linkage groups, than expected.
      Therefore parts of the A. barbata genome remain unmapped, possibly because they
      lack variation between the ecotypes. Nevertheless, we identified QTL
      (quantitative trait loci) under selection in both native environments and in the
      greenhouse. Across years at the same site, the same loci remain under selection,
      for the same alleles. Across sites, an overlapping set of loci are under
      selection with either (i) the same alleles favoured at both sites or (ii) loci
      under selection at one site and neutral at the other. QTL under selection in the
      greenhouse were generally unlinked to those under selection in the field because
      selection acted on a different trait. We found little evidence that selection
      favours alternate alleles in alternate environments, which would be necessary if
      genotype by environment interaction were to maintain genetic variation in A.
      barbata. Additive effect QTL were best able to explain the genetic variation
      among recombinant inbred lines for the greenhouse environment where heritability
      was highest, and past selection had not eliminated variation.

PMID- 16626457
TI  - Effect of genotype and environment on branching in weedy green millet (Setaria
      viridis) and domesticated foxtail millet (Setaria italica) (Poaceae).
AB  - Many domesticated crops are derived from species whose life history includes
      weedy characteristics, such as the ability to vary branching patterns in response
      to environmental conditions. However, domesticated crop plants are characterized
      by less variable plant architecture, as well as by a general reduction in
      vegetative branching compared to their progenitor species. Here we examine weedy
      green millet and its domesticate foxtail millet that differ in the number of
      tillers (basal branches) and axillary branches along each tiller. Branch number
      in F(2:3) progeny of a cross between the two species varies with genotype,
      planting density, and other environmental variables, with significant genotype
      environment interactions (GEI). This is shown by a complex pattern of reaction
      norms and by variation in the pattern of significant quantitative trait loci
      (QTL) amongst trials. Individual and joint analyses of high and low density
      trials indicate that most QTL have significant GEI. Dominance and epistasis also
      explain some variation in branching. Likely candidate genes underlying the QTL
      (based on map position and phenotypic effect) include teosinte branched1 and
      barren stalk1. Phytochrome B, which has been found to affect response to shading
      in other plants, explains little or no variation. Much variation in branching is
      explained by QTL that do not have obvious candidate genes from maize or rice.

PMID- 16626458
TI  - Natural genetic variation in whole-genome expression in Arabidopsis thaliana: the
      impact of physiological QTL introgression.
AB  - A long-standing and fundamental question in biology is how genes influence
      complex phenotypes. Combining near-isogenic line mapping with genome expression
      profiling offers a unique opportunity for exploring the functional relationship
      between genotype and phenotype and for generating candidate genes for future
      study. We used a whole-genome microarray produced with ink-jet technology to
      measure the relative expression level of over 21,500 genes from an Arabidopsis
      thaliana near-isogenic line (NIL) and its recurrent parent. The NIL material
      contained two introgressions (bottom of chromosome II and top of chromosome III)
      of the Cvi-1 ecotype in a Ler-2 ecotype genome background. Each introgression
      'captures' a Cvi allele of a physiological quantitative trait loci (QTL) that our
      previous studies have shown increases transpiration and reduces water-use
      efficiency at the whole-plant level. We used a mixed model anova framework for
      assessing sources of expression variability and for evaluating statistical
      significance in our array experiment. We discovered 25 differentially expressed
      genes in the introgression at a false-discovery rate (FDR) cut-off of 0.20 and
      identified new candidate genes for both QTL regions. Several differentially
      expressed genes were confirmed with QRT-PCR (quantitative reverse transcription
      polymerase chain reaction) assays. In contrast, we found no statistically
      significant differentially expressed genes outside of the QTL introgressions
      after controlling for multiple tests. We discuss these results in the context of
      candidate genes, cloning QTL, and phenotypic evolution.

PMID- 16626459
TI  - Use of Ecotilling as an efficient SNP discovery tool to survey genetic variation
      in wild populations of Populus trichocarpa.
AB  - Abstract Ecotilling was used as a simple nucleotide polymorphism (SNP) discovery
      tool to examine DNA variation in natural populations of the western black
      cottonwood, Populus trichocarpa, and was found to be more efficient than
      sequencing for large-scale studies of genetic variation in this tree. A publicly
      available, live reference collection of P. trichocarpa from the University of
      British Columbia Botanical Garden was used in this study to survey variation in
      nine different genes among individuals from 41 different populations. A large
      amount of genetic variation was detected, but the level of variation appears to
      be less than in the related species, Populus tremula, based on reported
      statistics for that tree. Genes examined varied considerably in their level of
      variation, from PoptrTB1 which had a single SNP, to PoptrLFY which had more than
      23 in the 1000-bp region examined. Overall nucleotide diversity, measured as
      (Total), was relatively low at 0.00184. Linkage disequilibrium, on the other
      hand, was higher than reported for some woody plant species, with mean r2 equal
      to 0.34. This study reveals the potential of Ecotilling as a rapid genotype
      discovery method to explore and utilize the large pool of genetic variation in
      tree species.

PMID- 16626460
TI  - A genetic similarity rule determines arthropod community structure.
AB  - We define a genetic similarity rule that predicts how genetic variation in a
      dominant plant affects the structure of an arthropod community. This rule applies
      to hybridizing cottonwood species where plant genetic variation determines plant
      animal interactions and structures a dependent community of leaf-modifying
      arthropods. Because the associated arthropod community is expected to respond to
      important plant traits, we also tested whether plant chemical composition is one
      potential intermediate link between plant genes and arthropod community
      composition. Two lines of evidence support our genetic similarity rule. First, in
      a common garden experiment we found that trees with similar genetic compositions
      had similar chemical compositions and similar arthropod compositions. Second, in
      a wild population, we found a similar relationship between genetic similarity in
      cottonwoods and the dependent arthropod community. Field data demonstrate that
      the relationship between genes and arthropods was also significant when the
      hybrids were analysed alone, i.e. the pattern is not dependent upon the inclusion
      of both parental species. Because plant-animal interactions and natural
      hybridization are common to diverse plant taxa, we suggest that a genetic
      similarity rule is potentially applicable, and may be extended, to other systems
      and ecological processes. For example, plants with similar genetic compositions
      may exhibit similar litter decomposition rates. A corollary to this genetic
      similarity rule predicts that in systems with low plant genetic variability, the
      environment will be a stronger factor structuring the dependent community. Our
      findings argue that the genetic composition of a dominant plant can structure
      higher order ecological processes, thus placing community and ecosystem ecology
      within a genetic and evolutionary framework. A genetic similarity rule also has
      important conservation implications because the loss of genetic diversity in one
      species, especially dominant or keystone species that define many communities,
      may cascade to negatively affect the rest of the dependent community.

PMID- 16626461
TI  - Integrating biogeographic and genetic approaches to investigate the history of
      bioluminescent colour alleles in the Jamaican click beetle, Pyrophorus
      plagiophthalamus.
AB  - Bioluminescent colour in the Jamaican click beetle, Pyrophorus plagiophthalamus,
      is an ideal system for studies moving from gene to landscape to gain a holistic
      understanding of the molecular, ecological, and historical bases for adaptation.
      Previous studies have established the genetics of bioluminescent colour variation
      in the beetle to the level of the nucleotide base pair in the target gene
      luciferase. Three different luciferase colour alleles affecting ventral light
      organ colour [yellow-green (vYG), yellow (vYE), and orange (vOR)] were found
      segregating in P. plagiophthalamus populations. These alleles differ from each
      other in a number of replacement mutations (14 total), the majority of which (11)
      have a measurable effect on colour. Phylogenetic analysis revealed a long-term
      adaptive trend on Jamaica towards longer wavelength bioluminescence, culminating
      in the most recently derived vOR allele. Here, we further investigate the
      historical and geographic context of adaptive colour evolution by testing a
      vicariance model for the origins of the extant ventral light organ polymorphism:
      that the vOR allele arose and differentiated in an isolated deme on the east side
      of Jamaica before spreading westward. Comparisons of colour phenotypes,
      luciferase coding sequences, the third intron of the gene, mtDNA, and
      microsatellite data provided evidence for past population subdivision on Jamaica
      and ongoing gene flow, as has been found for other island endemics. However, the
      pattern of differentiation supported the allopatric divergence of vYG and vYE
      alleles. The vOR gene appears to have arisen relatively recently from a vYE
      precursor and postdates the period of major biogeographic isolation. We discuss
      the implications of the results for discerning ecological causation in the
      adaptive sequence from nucleotide to landscape to population change for
      bioluminescent colour.

PMID- 16626462
TI  - Distribution of genetic variation within and among local populations of
      Arabidopsis thaliana over its species range.
AB  - A detailed description of local population structure in Arabidopsis thaliana is
      presented, including an assessment of the genetic relatedness of individuals
      collected from the same field. A hierarchical sample of four individuals from 37
      local populations, including North America, England, Eastern and Western Europe,
      and Asia, and a selection of ecotypes, were analysed for variation in Adh, ChiA,
      FAH1, F3H, Rpm1, Rps5, and five microsatellite loci. Twenty-eight of the 37
      population samples contained individuals with identical multilocus haplotypes, 12
      of which were fixed for a single haplotype. These monomorphic populations were
      evenly distributed over the species range. Only in North America did we find a
      single multilocus haplotype shared among different populations, perhaps
      indicating a continental founder event. Despite the occurrence of local
      inbreeding, a considerable amount of genetic variation was found segregating
      within and among local populations. A novel analysis of haplotype differences
      reveals that genetic differentiation occurs at every geographic scale in A.
      thaliana, where we find a surprising under-representation of recent migrants
      between local populations. This leads us to hypothesize that most dispersal
      between A. thaliana populations is by pollen rather than seed. Based on the
      structure of A. thaliana populations, it appears that regional groups of local
      populations may provide the most appropriate genetic material for linkage
      disequilibrium mapping of adaptive traits.

PMID- 16626463
TI  - The surprising diversity of ascomycetous mycorrhizas.

PMID- 16626464
TI  - Herbivory tolerance and coevolution: an alternative to the arms race?

PMID- 16626465
TI  - Scale and scalability.

PMID- 16626466
TI  - Letting the gene out of the bottle: the population genetics of genetically
      modified crops.
AB  - Genetically modified (GM) plants are rapidly becoming a common feature of modern
      agriculture. This transition to engineered crops has been driven by a variety of
      potential benefits, both economic and ecological. The increase in the use of GM
      crops has, however, been accompanied by growing concerns regarding their
      potential impact on the environment. Here, we focus on the escape of transgenes
      from cultivation via crop x wild hybridization. We begin by reviewing the
      literature on natural hybridization, with particular reference to gene flow
      between crop plants and their wild relatives. We further show that natural
      selection, and not the overall rate of gene flow, is the most important factor
      governing the spread of favorable alleles. Hence, much of this review focuses on
      the likely effects of transgenes once they escape. Finally, we consider
      strategies for transgene containment.

PMID- 16626467
TI  - Soil biota and invasive plants.
AB  - Interactions between plants and soil biota resist invasion by some nonnative
      plants and facilitate others. In this review, we organize research and ideas
      about the role of soil biota as drivers of invasion by nonnative plants and how
      soil biota may fit into hypotheses proposed for invasive success. For example,
      some invasive species benefit from being introduced into regions of the world
      where they encounter fewer soil-borne enemies than in their native ranges. Other
      invasives encounter novel but strong soil mutualists which enhance their invasive
      success. Leaving below-ground natural enemies behind or encountering strong
      mutualists can enhance invasions, but indigenous enemies in soils or the absence
      of key soil mutualists can help native communities resist invasions. Furthermore,
      inhibitory and beneficial effects of soil biota on plants can accelerate or
      decelerate over time depending on the net effect of accumulating pathogenic and
      mutualistic soil organisms. These 'feedback' relationships may alter plant-soil
      biota interactions in ways that may facilitate invasion and inhibit re
      establishment by native species. Although soil biota affect nonnative plant
      invasions in many different ways, research on the topic is broadening our
      understanding of why invasive plants can be so astoundingly successful and
      expanding our perspectives on the drivers of natural community organization.

PMID- 16626468
TI  - Preferential localization of abscisic acid in primordial and nursing cells of
      reproductive organs of Arabidopsis and cucumber.
AB  - Abscisic acid (ABA) is known to function in plant stress responses and seed
      dormancy, and much is known about its detailed mechanisms of signal transduction.
      Recent studies suggest that this hormone may also play important roles in sugar
      signaling and assimilate distribution during fruit development. However, little
      is known about the role of ABA in actively growing or differentiating fruits and
      other plant organs or tissues. To explore whether ABA functions during the early
      development of reproductive organs, we carried out ABA immunolocalization using
      monoclonal antibodies. The specific ABA accumulation pattern was verified by gas
      chromatography-mass spectrometry (GC-MS). ABA was not only detected in primordial
      cells of flower organs, but was also detected in nursing cells (e.g. tapetum and
      integuments), which function in supplying nutrition for germ cell development.
      These findings suggest that, in addition to its well-known function as a
      'negative hormone', ABA may play some 'positive' roles during plant development,
      including possible involvement in the regulation of assimilate distribution.

PMID- 16626469
TI  - Genetic basis of phenotypic correlations among growth traits in hybrid willow
      (Salix dasycladosxS. viminalis) grown under two water regimes.
AB  - Phenotypic correlations and quantitative trait loci (QTL) for important growth
      traits and a surrogate of intrinsic water-use efficiency (leaf delta(13)C) were
      analysed in a willow pedigree of 92 full-sibling clones grown under two water
      regimes. The major objective was to examine the genetic basis of the phenotypic
      correlations. Cuttings of Salix were glasshouse-grown during one growing season.
      The relative growth rate (RGR) and underlying traits were assessed. QTL analysis
      was conducted based on an available linkage map for Salix. Leaf area productivity
      and leaf nitrogen productivity were more important in determining RGR than leaf
      area ratio and specific leaf area. However, phenotypic correlations among growth
      traits partly varied between the two environments. QTL were detected for most
      growth traits, among them many common QTL for different traits. The QTL pattern
      reflected the phenotypic correlation pattern. None of the QTL for the complex
      traits was consistent across the different environments. The results demonstrate
      a genetic basis for phenotypic correlations among growth traits in Salix, and
      provide evidence for the existence of 'master switches' regulating some of the
      traits.

PMID- 16626470
TI  - Assimilation and allocation of carbon and nitrogen of thermal and nonthermal
      Agrostis species in response to high soil temperature.
AB  - We studied whether changes in the assimilation and allocation of carbon and
      nitrogen are associated with plant tolerance to high soil temperatures. Two
      Agrostis species, thermal Agrostis scabra, a species adapted to high-temperature
      soils in geothermal areas in Yellowstone National Park (USA), and two cultivars
      of a cool-season species, Agrostis stolonifera, L-93 and Penncross, were exposed
      to soil temperatures of 37 or 20 degrees C, while shoots were exposed to 20
      degrees C. Net photosynthesis rate, photochemical efficiency, NO(3) (-)
      assimilation rate and root viability decreased with increasing soil temperatures
      in both species. However, the decreases were less pronounced for A. scabra than
      for both A. stolonifera cultivars. Carbon investment in growth of plants exposed
      to 37 degrees C decreased more dramatically in both A. stolonifera cultivars than
      in A. scabra. Nitrogen allocation to shoots was greater in A. scabra than in both
      creeping bentgrass cultivars at 37 degrees C soil temperature. Our results
      demonstrate that plant tolerance to high soil temperature is related to efficient
      expenditure and adjustment of C- and N-allocation patterns between growth and
      respiration.

PMID- 16626471
TI  - Functional significance of dauciform roots: exudation of carboxylates and acid
      phosphatase under phosphorus deficiency in Caustis blakei (Cyperaceae).
AB  - Caustis blakei produces an intriguing morphological adaptation by inducing
      dauciform roots in response to phosphorus (P) deficiency. We tested the
      hypothesis that these hairy, swollen lateral roots play a similar role to cluster
      roots in the exudation of organic chelators and ectoenzymes known to aid the
      chemical mobilization of sparingly available soil nutrients, such as P. Dauciform
      root development and exudate composition (carboxylates and acid phosphatase
      activity) were analysed in C. blakei plants grown in nutrient solution under P
      starved conditions. The distribution of dauciform roots in the field was
      determined in relation to soil profile depth and matrix. The percentage of
      dauciform roots of the entire root mass was greatest at the lowest P
      concentration ([P]) in solution, and was suppressed with increasing solution [P],
      while in the field dauciform roots were predominantely located in the upper soil
      horizons, and decreased with increasing soil depth. Citrate was the major
      carboxylate released in an exudative burst from mature dauciform roots, which
      also produced elevated levels of acid phosphatase activity. Malonate was the
      dominant internal carboxylate present, with the highest concentration in young
      dauciform roots. The high concentration of carboxylates and phosphatases released
      from dauciform roots, combined with their prolific distribution in the organic
      surface layer of nutrient-impoverished soils, provides an ecophysiological
      advantage for enhancing nutrient acquisition.

PMID- 16626472
TI  - Modulation of reactive oxygen species activities and H2O2 accumulation during
      compatible and incompatible tomato-root-knot nematode interactions.
AB  - Here, the interaction of Melodoigyne incognita virulent and avirulent pathotypes
      with susceptible and Mi-resistant tomato (Solanum lycopersicon) has been studied.
      Significant differences in nematode penetration occurred 2 days postinoculation
      (dpi) and became stable from 3 dpi onwards. The hypersensitive cell response (HR)
      in resistant plants prevented the installation of the avirulent pathotype. The
      virulent pathotype overcame the Mi (nematode) resistance and induced feeding
      sites in root cells without triggering HR. Reactive oxygen species (ROS),
      visualized by subcellular reduction of nitroblue tetrazolium, accumulated in
      nematode penetrated cells. Quantitative analyses with dichlorofluorescein
      indicated that the oxidative burst occurred very early with both pathotypes, with
      an enhanced rate in hyper-responsive cells. Hydrogen peroxide (H(2)O(2)),
      detected by cerium chloride reaction, accumulated in the cell walls and
      especially in cells neighbouring HR. The apoplastic location of cerium
      perhydroxide indicated that either the plasma membrane or the cell wall was the
      primary site of the superoxide/H(2)O(2) generator. The data provide evidence, for
      the first time, for ROS-generated signals and their spatiotemporal expression in
      the host and nonhost interaction of tomato with nematodes.

PMID- 16626473
TI  - Grass-herbivore interactions altered by strains of a native endophyte.
AB  - Many plants support symbiotic microbes, such as endophytic fungi, that can alter
      interactions with herbivores. Most endophyte research has focused on
      agronomically important species, with less known about the ecological roles of
      native endophytes in native plants. In particular, whether genetic variation
      among endophyte symbionts affects herbivores of plant hosts remains unresolved
      for most native endophytes. Here, we investigate the importance of native
      isolates of the endophyte Epichloe elymi in affecting herbivory of the native
      grass host, Elymus hystrix. Experimental fungal isolate-plant genotype
      combinations and endophyte-free control plants were grown in a common garden and
      exposed to natural arthropod herbivory. Fungal isolates differed in their effects
      on two types of herbivory, chewing and scraping. Isolates exhibiting greater
      sexual reproduction were associated with greater herbivore damage than primarily
      asexual isolates. Endophyte infection also altered patterns of herbivory within
      plants, with stroma-bearing tillers experiencing up to 30% greater damage than
      nonstroma-bearing tillers. Results suggest that intraspecific genetic variation
      in endophytes, like plant genetic variation, can have important 'bottom-up'
      effects on herbivores in native systems.

PMID- 16626474
TI  - A cDNA microarray approach to decipher sunflower (Helianthus annuus) responses to
      the necrotrophic fungus Phoma macdonaldii.
AB  - To identify the genes involved in the partial resistance of sunflower (Helianthus
      annuus) to the necrotrophic fungus Phoma macdonaldii, we developed a 1000-element
      cDNA microarray containing carefully chosen genes putatively involved in primary
      metabolic pathways, signal transduction and biotic stress responses. A two-pass
      general linear model was used to normalize the data and then to detect
      differentially expressed genes. This method allowed us to identify 38 genes
      differentially expressed among genotypes, treatments and times, mainly belonging
      to plant defense, signaling pathways and amino acid metabolism. Based on a set of
      genes whose differential expression was highly significant, we propose a model in
      which negative regulation of a dual-specificity MAPK phosphatase could be
      implicated in sunflower defense mechanisms against the pathogen. The resulting
      activation of the MAP kinase cascade could subsequently trigger defense responses
      (e.g. thaumatin biosynthesis and phenylalanine ammonia lyase activation), under
      the control of transcription factors belonging to MYB and WRKY families.
      Concurrently, the activation of protein phosphatase 2A (PP2A), which is
      implicated in cell death inhibition, could limit pathogen development. The
      results reported here provide a valuable first step towards the understanding and
      analysis of the P. macdonaldii-sunflower interaction.

PMID- 16626475
TI  - Characterization of a new, nonpathogenic mutant of Botrytis cinerea with impaired
      plant colonization capacity.
AB  - Botrytis cinerea is a necrotrophic pathogen that attacks more than 200 plant
      species. Here, the nonpathogenic mutant A336, obtained via insertional
      mutagenesis, was characterized. Mutant A336 was nonpathogenic on leaves and
      fruits, on intact and wounded tissue, while still able to penetrate the host
      plant. It grew normally in vitro on rich media but its conidiation pattern was
      altered. The mutant did not produce oxalic acid and exhibited a modified
      regulation of the production of some secreted proteins (acid protease 1 and
      endopolygalacturonase 1). Culture filtrates of the mutant triggered an important
      oxidative burst in grapevine (Vitis vinifera) suspension cells, and the mutant
      plant interaction resulted in the formation of hypersensitive response-like
      necrosis. Genetic segregation analyses revealed that the pathogenicity phenotype
      was linked to a single locus, but showed that the mutated gene was not tagged by
      the plasmid pAN7-1. Mutant A336 is the first oxalate-deficient mutant to be
      described in B. cinerea and it differs from all the nonpathogenic B. cinerea
      mutants described to date.

PMID- 16626476
TI  - The effect of different pine hosts on the sampling of Rhizopogon spore banks in
      five Eastern Sierra Nevada forests.
AB  - Our primary goal was to determine whether detection of Rhizopogon internal
      transcribed spacer (ITS) groups is affected by the pine species used in seedling
      bioassays. Our secondary goal was to investigate composition of Rhizopogon spore
      banks in the Eastern Sierra Nevada of California, a previously unsampled region.
      We used seedlings of Pinus contorta, Pinus jeffreyi, Pinus lambertiana, and Pinus
      muricata as bioassay plants and identified the Rhizopogon retrieved by internal
      transcribed spacer (ITS) sequence analysis. We found that each of the pine
      species retrieved all of the abundant Rhizopogon ITS groups, but there were
      significant differences among pines in the richness of Rhizopogon ITS groups
      recovered. Pinus muricata recovered all ITS groups found in this study and was
      significantly better than P. lambertiana. Rhizopogon communities from the five
      sampled sites contained six to eight ITS groups per site, with two unique
      sequence groups and a higher abundance of the Rhizopogon ellenae and Rhizopogon
      arctostaphyli groups than at previously sampled sites. These results show high
      cross-receptivity between Rhizopogon and pine species, and regional patterns in
      spore bank composition.

PMID- 16626477
TI  - Mast fruiting of large ectomycorrhizal African rain forest trees: importance of
      dry season intensity, and the resource-limitation hypothesis.
AB  - Mast fruiting is a distinctive reproductive trait in trees. This rain forest
      study, at a nutrient-poor site with a seasonal climate in tropical Africa,
      provides new insights into the causes of this mode of phenological patterning. At
      Korup, Cameroon, 150 trees of the large, ectomycorrhizal caesalp, Microberlinia
      bisulcata, were recorded almost monthly for leafing, flowering and fruiting
      during 1995-2000. The series was extended to 1988-2004 with less detailed data.
      Individual transitions in phenology were analysed. Masting occurred when the dry
      season before fruiting was drier, and the one before that was wetter, than
      average. Intervals between events were usually 2 or 3 yr. Masting was associated
      with early leaf exchange, followed by mass flowering, and was highly synchronous
      in the population. Trees at higher elevation showed more fruiting. Output
      declined between 1995 and 2000. Mast fruiting in M. bisulcata appears to be
      driven by climate variation and is regulated by internal tree processes. The
      resource-limitation hypothesis was supported. An 'alternative bearing' system
      seems to underlie masting. That ectomycorrhizal habit facilitates masting in
      trees is strongly implied.

PMID- 16626478
TI  - Molecular and morphological diversity of pezizalean ectomycorrhiza.
AB  - A growing body of molecular research is discovering a high diversity of
      pezizalean ectomycorrhiza (EcM), yet most remain unidentified at the genus or
      species level. This study describes EcM-forming taxa within the Pezizales. EcM
      forming Pezizales were revealed by morphotyping and sequencing of EcM root tips
      from forests in Estonia and Denmark. The taxa on EcM root tips were identified
      using phylogenetic analyses of large-subunit rDNA sequences derived from
      sporocarps of 301 pezizalean species, and comparisons with internal transcribed
      spacer rDNA sequences. Thirty-three species are suggested as EcM symbionts,
      representing all three major clades of Pezizales, the genera Genea, Geopora,
      Humaria, Tarzetta, Trichophaea, Wilcoxina, Helvella, Hydnotrya, Tuber,
      Pachyphloeus, Peziza and Sarcosphaera, and two Pezizaceae anamorphs. EcM of
      Pezizales species are easily distinguished by their anatomy, particularly thick
      cell walls and stout hyphae. This study demonstrates that Pezizales species
      constitute a considerable proportion of the mycobionts in EcM fungal communities
      in mature boreal deciduous and coniferous forests, in several soil types. Fruit
      body sequences and EcM descriptions will facilitate identification of pezizalean
      EcM in future studies.

PMID- 16626479
TI  - Pseudocyphellaria crocata, P. neglecta and P. perpetua from the Northern and
      Southern Hemispheres are a phylogenetic species and share cyanobionts.
AB  - Pseudocyphellaria crocata, P. neglecta and P. perpetua specimens were examined to
      investigate links between genetic variation and morphology, geographical
      distribution and cyanobiont specificity. Fungal internal transcribed spacer
      (ITS), beta-tubulin and cyanobacterial tRNA(Leu) (UAA) intron sequences were used
      to investigate symbiont diversity in these lichens. Specimens were
      morphologically distinct but could not be distinguished by ITS sequences.
      Phylogenetic analyses split the P. crocata specimens into two clades, the larger
      of which contained P. neglecta and P. perpetua. Five cyanobionts were identified;
      two of these were in a number of specimens, while three were each restricted to a
      single lichen thallus. Fungus-specific molecular markers indicated that all
      specimens belonged to a single phylogenetic species. However, this may contain a
      cryptic species. Geography was linked to genetic diversity with Canadian
      specimens forming a monophyletic group, and most Southern Hemisphere specimens
      grouping together, although Chile represented a hot spot of genetic diversity.
      There was no connection between fungal genetic diversity and cyanobiont choice,
      consistent with the presence of a common pool of cyanobionts.

PMID- 16626480
TI  - Host tolerance does not impose selection on natural enemies.
AB  - Coevolution between hosts and their natural enemies is believed to operate
      through the evolution of resistance traits. Although the importance of tolerance
      to natural enemies as an alternative defensive strategy has been recognized,
      there is still no consensus about the possible role of host tolerance in the
      evolutionary outcome of the interaction. Here, using bioassay experiments, we
      tested the hypothesis that variation in host tolerance among selected plant
      genotypes could impose a selection pressure upon a specialist herbivore.
      Tolerance did not affect herbivore larvae survival, weight gain, efficiency of
      food consumption, total food consumption, developmental time and adult mass.
      These results therefore do not support the hypothesis that host tolerance could
      affect natural enemy performance. However, resistance did negatively affect
      herbivore larva survival. Genetic variation in herbivore larva survival was
      detected, thus suggesting the potential for a coevolutionary response. Our
      results indicate that host tolerance would reduce opportunities for a
      coevolutionary response by the natural enemies of the host. Contrary to
      predictions from previous models, our results suggest that host tolerance may
      constitute an evolutionarily unstable defensive strategy.

PMID- 16626481
TI  - Response to salinity in the homoploid hybrid species Helianthus paradoxus and its
      progenitors H. annuus and H. petiolaris.
AB  - To contribute to the understanding of ecological differentiation in speciation,
      we compared salinity responses of the halophytic diploid hybrid species
      Helianthus paradoxus and its glycophytic progenitors Helianthus annuus and
      Helianthus petiolaris. Plants of three populations of each species were subjected
      to a control (nonsaline) and three salinity treatments, including one simulating
      the ion composition in the habitat of H. paradoxus. Relative to the control,
      saline treatments led to a 17% biomass increase in H. paradoxus while its
      progenitors suffered 19-33% productivity reductions and only in H. paradoxus,
      leaf contents of potassium, calcium, and magnesium were strongly reduced. Under
      all treatments, H. paradoxus allocated more resources to roots, was more
      succulent, and had higher leaf contents of sodium (> 200 mmol l(-1) tissue water)
      and sulfur than its progenitor species. These results suggest that salt tolerance
      and thus speciation of H. paradoxus is related to sodium replacing potassium,
      calcium and magnesium as vacuolar osmotica. The evolutionary and genetic
      mechanisms likely to be involved are discussed.

PMID- 16626482
TI  - Quantifying species composition in root mixtures using two methods: near-infrared
      reflectance spectroscopy and plant wax markers.
AB  - Understanding of plant interactions is greatly limited by our ability to identify
      and quantify roots belonging to different species. We proposed and compared two
      methods for estimating the root biomass proportion of each species in artificial
      mixtures: near-infrared reflectance spectroscopy (NIRS) and plant wax markers.
      Two sets of artificial root mixtures composed of two or three herbaceous species
      were prepared. The proportion of root material of each species in mixtures was
      estimated from NIRS spectral data (i) and the concentration patterns of n-alkanes
      (ii), n-alcohols (iii), and n-alkanes +n-alcohols combined (iv). For each data
      set, calibration equations were developed using multivariate statistical models.
      The botanical composition of root mixtures was predicted well for all the species
      considered. The accuracy varied slightly among methods: alkanes < alcohols =
      alkanes + alcohols < NIRS. Correlation coefficients between predicted and actual
      root proportions ranged from 0.89 to 0.99 for alkanes + alcohols predictions and
      from 0.97 to 0.99 for NIRS predictions. These two methods provide promising
      potential for understanding allocation patterns and competitive interactions.

PMID- 16626483
TI  - Discovery, linkage disequilibrium and association analyses of polymorphisms of
      the immune complement inhibitor, decay-accelerating factor gene (DAF/CD55) in
      type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a common autoimmune disease resulting from T
      cell mediated destruction of pancreatic beta cells. Decay accelerating factor
      (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a
      candidate for autoimmune disease susceptibility based on its role in restricting
      complement activation and evidence that DAF expression modulates the phenotype of
      mice models for autoimmune disease. In this study, we adopt a linkage
      disequilibrium (LD) mapping approach to test for an association between the DAF
      gene and T1D. RESULTS: Initially, we used HapMap II genotype data to examine LD
      across the DAF region. Additional resequencing was required, identifying 16 novel
      polymorphisms. Combining both datasets, a LD mapping approach was adopted to test
      for association with T1D. Seven tag SNPs were selected and genotyped in case
      control (3,523 cases and 3,817 controls) and family (725 families) collections.
      CONCLUSION: We obtained no evidence of association between T1D and the DAF region
      in two independent collections. In addition, we assessed the impact of using only
      HapMap II genotypes for the selection of tag SNPs and, based on this study, found
      that HapMap II genotypes may require additional SNP discovery for comprehensive
      LD mapping of some genes in common disease.

PMID- 16626484
TI  - The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt.
AB  - BACKGROUND: Serotonergic neurotransmission has been implicated in suicidal
      behavior. Association between suicidal completers and a regulatory C(-1019)G
      polymorphism (rs6295) in the serotonin 1A receptor (HTR1A) gene was previously
      reported, whereas a following study showed no association in a sample of suicide
      attempters. METHODS: The involvement of the implicated G-allele of the 5-HTR1A C(
      1019)G polymorphism (rs6295) was analyzed with the transmission disequilibrium
      test (TDT) in a sample of 272 suicide attempter families. RESULTS: No
      overtransmission of the G-allele was found in the entire sample of suicide
      attempters (p = 0.1460; n = 272 trios). However, a strong trend for
      overtransmission of the G-allele was observed in a sub-sample selected for a high
      level of previous traumatic and/or stressful life events prior to the suicide
      attempt (p = 0.0630, two-tail; n = 94 trios). CONCLUSION: The current results
      show that variation at the rs6295 polymorphism of the HTR1A gene is not
      associated with suicide attempts generally. However, the results indicate a
      possible role of the G-allele in suicidal behavior in connection with high
      exposure to traumatic and/or stressful life events, which is in need of future
      investigation.

PMID- 16626485
TI  - A FERM-adjacent (FA) region defines a subset of the 4.1 superfamily and is a
      potential regulator of FERM domain function.
AB  - BACKGROUND: Proteins containing FERM domains comprise a diverse group of
      eukaryotic proteins that bind membrane proteins and lipids. In doing so, they
      organise membrane microstructure, and coordinate the disposition of signalling
      and cell adhesion complexes. In protein 4.1R, phosphorylation adjacent to the
      FERM domain regulates its activity, and membrane mechanical properties. RESULTS:
      A novel sequence domain has been detected in a subset of proteins that contain
      FERM domains. This subset includes the true 4.1 proteins, some tyrosine
      phosphatases, rho-GEF proteins and type II transmembrane proteins, as well as
      some uncharacterised FERM proteins. This FERM-adjacent region is always closely
      proximate to the C-terminal of the FERM domain. This sequence is likely to be
      folded with elements of alpha and beta structure. The FERM-adjacent region of
      4.1R contains serine residues phosphorylated by PKC and PKA; these appear
      conserved in about half of all other FERM-adjacent regions. Phylogenetic analyses
      indicate that all proteins containing a FERM-adjacent region arose from a single
      ancestor after FERM domains had started to proliferate in genomes of animals,
      plants and mycetozoa. CONCLUSION: The FERM-adjacent region defines a subset of
      the FERM proteins in animals. The conservation of motifs in this region that are
      potential substrates for kinases together with the known regulatory
      phosphorylation of 4.1R in this region raises the possibility that the FERM
      adjacent region is a regulatory adaptation in this subset of the FERM proteins.

PMID- 16626486
TI  - Lactate: creatinine ratio in babies with thin meconium staining of amniotic
      fluid.
AB  - BACKGROUND: ACOG states meconium stained amniotic fluid (MSAF) as one of the
      historical indicators of perinatal asphyxia. Thick meconium along with other
      indicators is used to identify babies with severe intrapartum asphyxia. Lactate
      creatinine ratio (L:C ratio) of 0.64 or higher in first passed urine of babies
      suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic
      Encephalopathy (HIE). Literature review shows that meconium is passed in distress
      and thin meconium results from mixing and dilution over time, which may be hours
      to days. Thin meconium may thus be used as an indicator of antepartum asphyxia.
      We tested L:C ratios in a group of babies born through thin and thick meconium,
      and for comparison, in a group of babies without meconium at birth. METHODS: 86
      consecutive newborns, 36 to 42 weeks of gestation, with meconium staining of
      liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of
      these 27 had thick meconium and 25 had thin meconium at birth. 42 others, who did
      not have meconium or any other signs of asphyxia at birth provided controls.
      Lactate and creatinine levels in urine were tested by standard enzymatic methods
      in the three groups. RESULTS: Lactate values are highest in the thin MSAF group
      followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF,
      followed by thick MSAF and controls. Normal babies had an average L:C ratio of
      0.13 (+/- 0.09). L:C ratio was more among thin MSAF babies (4.3 +/- 11.94) than
      thick MSAF babies (0.35 +/- 0.35). Median L:C ratio was also higher in the thin
      MSAF group. Variation in the values of these parameters is observed to be high in
      the thin MSAF group as compared to other groups. L:C ratio was above the cutoff
      of 0.64 of Huang et al in 40% of those with thin meconium. 2 of these developed
      signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital
      stay. One had L:C Ratio of 93 and the other of 58.6. A smaller proportion (20%)
      of those with thick meconium had levels above the cutoff and 2 developed HIE and
      convulsions with L:C ratio of 1.25 and 1.1 respectively. CONCLUSION: In evolving
      a cutoff of L:C ratios that would be highly sensitive and specific (0.64), Huang
      et al studied it in a series of babies with severe intrapartum asphyxia. Our
      study shows that the specificity may not be as good if babies born through thin
      meconium are also included. L:C ratios are much higher in babies with thin
      meconium. It may be that meconium alone is not a good indicator of asphyxia and
      the risk of HIE. However, if the presence of meconium implies asphyxia then
      perhaps a higher cut-off than 0.64 is needed. L:C ratios should be tested in a
      larger sample that includes babies with thin meconium, before L:C ratios can be
      applied universally.

PMID- 16626487
TI  - The photocurrent response of human cones is fast and monophasic.
AB  - BACKGROUND: The precise form of the light response of human cone photoreceptors
      in vivo has not been established with certainty. To investigate the response
      shape we compare the predictions of a recent model of transduction in primate
      cone photoreceptors with measurements extracted from human cones using the paired
      flash electroretinogram method. As a check, we also compare the predictions with
      previous single-cell measurements of ground squirrel cone responses. RESULTS: The
      predictions of the model provide a good description of the measurements, using
      values of parameters within the range previously determined for primate retina.
      The dim-flash response peaks in about 20 ms, and flash responses at all
      intensities are essentially monophasic. Three time constants in the model are
      extremely short: the two time constants for inactivation (of visual pigment and
      of transducin/phosphodiesterase) are around 3 and 10 ms, and the time constant
      for calcium equilibration lies in the same range. CONCLUSION: The close
      correspondence between experiment and theory, using parameters previously derived
      for recordings from macaque retina, supports the notion that the
      electroretinogram approach and the modelling approach both provide an accurate
      estimate of the cone photoresponse in the living human eye. For reasons that
      remain unclear, the responses of isolated photoreceptors from the macaque retina,
      recorded previously using the suction pipette method, are considerably slower
      than found here, and display biphasic kinetics.

PMID- 16626488
TI  - On pandemics and the duty to care: whose duty? who cares?
AB  - BACKGROUND: As a number of commentators have noted, SARS exposed the
      vulnerabilities of our health care systems and governance structures. Health care
      professionals (HCPs) and hospital systems that bore the brunt of the SARS
      outbreak continue to struggle with the aftermath of the crisis. Indeed, HCPs -
      both in clinical care and in public health - were severely tested by SARS.
      Unprecedented demands were placed on their skills and expertise, and their
      personal commitment to their profession was severely tried. Many were exposed to
      serious risk of morbidity and mortality, as evidenced by the World Health
      Organization figures showing that approximately 30% of reported cases were among
      HCPs, some of whom died from the infection. Despite this challenge, professional
      codes of ethics are silent on the issue of duty to care during communicable
      disease outbreaks, thus providing no guidance on what is expected of HCPs or how
      they ought to approach their duty to care in the face of risk. DISCUSSION: In the
      aftermath of SARS and with the spectre of a pandemic avian influenza, it is
      imperative that we (re)consider the obligations of HCPs for patients with severe
      infectious diseases, particularly diseases that pose risks to those providing
      care. It is of pressing importance that organizations representing HCPs give
      clear indication of what standard of care is expected of their members in the
      event of a pandemic. In this paper, we address the issue of special obligations
      of HCPs during an infectious disease outbreak. We argue that there is a pressing
      need to clarify the rights and responsibilities of HCPs in the current context of
      pandemic flu preparedness, and that these rights and responsibilities ought to be
      codified in professional codes of ethics. Finally, we present a brief historical
      accounting of the treatment of the duty to care in professional health care codes
      of ethics. SUMMARY: An honest and critical examination of the role of HCPs during
      communicable disease outbreaks is needed in order to provide guidelines regarding
      professional rights and responsibilities, as well as ethical duties and
      obligations. With this paper, we hope to open the social dialogue and advance the
      public debate on this increasingly urgent issue.

PMID- 16626489
TI  - Do visual analogue scale (VAS) derived standard gamble (SG) utilities agree with
      Health Utilities Index utilities? A comparison of patient and community
      preferences for health status in rheumatoid arthritis patients.
AB  - BACKGROUND: Assessment of Health Related Quality of Life (HRQL) has become
      increasingly important and various direct and indirect methods and instruments
      have been devised to measure it. In direct methods such as Visual Analog Scale
      (VAS) and Standard Gamble (SG), respondent both assesses and values health states
      therefore the final score reflects patient's preferences. In indirect methods
      such as multi-attribute health status classification systems, the patient
      provides the assessment of a health state and then a multi-attribute utility
      function is used for evaluation of the health state. Because these functions have
      been estimated using valuations of general population, the final score reflects
      community's preferences. The objective of this study is to assess the agreement
      between community preferences derived from the Health Utilities Index Mark 2
      (HUI2) and Mark 3 (HUI3) systems, and patient preferences. METHODS: Visual analog
      scale (VAS) and HUI scores were obtained from a sample of 320 rheumatoid
      arthritis patients. VAS scores were adjusted for end-aversion bias and
      transformed to standard gamble (SG) utility scores using 8 different power
      conversion formulas reported in other studies. Individual level agreement between
      SG utilities and HUI2 and HUI3 utilities was assessed using the intraclass
      correlation coefficient (ICC). Group level agreement was assessed by comparing
      group means using the paired t-test. RESULTS: After examining all 8 different SG
      estimates, the ICC (95% confidence interval) between SG and HUI2 utilities ranged
      from 0.45 (0.36 to 0.54) to 0.55 (0.47 to 0.62). The ICC between SG and HUI3
      utilities ranged from 0.45 (0.35 to 0.53) to 0.57 (0.49 to 0.64). The mean
      differences between SG and HUI2 utilities ranged from 0.10 (0.08 to 0.12) to 0.22
      (0.20 to 0.24). The mean differences between SG and HUI3 utilities ranged from
      0.18 (0.16 to 0.2) to 0.28 (0.26 to 0.3). CONCLUSION: At the individual level,
      patient and community preferences show moderate to strong agreement, but at the
      group level they have clinically important and statistically significant
      differences. Using different sources of preference might alter clinical and
      policy decisions that are based on methods that incorporate HRQL assessment. VAS
      derived utility scores are not good substitutes for HUI scores.

PMID- 16626490
TI  - A GIS-driven integrated real-time surveillance pilot system for national West
      Nile virus dead bird surveillance in Canada.
AB  - BACKGROUND: An extensive West Nile virus surveillance program of dead birds,
      mosquitoes, horses, and human infection has been launched as a result of West
      Nile virus first being reported in Canada in 2001. Some desktop and web GIS have
      been applied to West Nile virus dead bird surveillance. There have been urgent
      needs for a comprehensive GIS services and real-time surveillance. RESULTS: A
      pilot system was developed to integrate real-time surveillance, real-time GIS,
      and Open GIS technology in order to enhance West Nile virus dead bird
      surveillance in Canada. Driven and linked by the newly developed real-time web
      GIS technology, this integrated real-time surveillance system includes
      conventional real-time web-based surveillance components, integrated real-time
      GIS components, and integrated Open GIS components. The pilot system identified
      the major GIS functions and capacities that may be important to public health
      surveillance. The six web GIS clients provide a wide range of GIS tools for
      public health surveillance. The pilot system has been serving Canadian national
      West Nile virus dead bird surveillance since 2005 and is adaptable to serve other
      disease surveillance. CONCLUSION: This pilot system has streamlined, enriched and
      enhanced national West Nile virus dead bird surveillance in Canada, improved
      productivity, and reduced operation cost. Its real-time GIS technology, static
      map technology, WMS integration, and its integration with non-GIS real-time
      surveillance system made this pilot system unique in surveillance and public
      health GIS.

PMID- 16626491
TI  - Performance of a new hand-held device for exhaled nitric oxide measurement in
      adults and children.
AB  - BACKGROUND: Exhaled nitric oxide (NO) measurement has been shown to be a valuable
      tool in the management of patients with asthma. Up to now, most measurements have
      been done with stationary, chemiluminescence-based NO analysers, which are not
      suitable for the primary health care setting. A hand-held NO analyser which
      simplifies the measurement would be of value both in specialized and primary
      health care. In this study, the performance of a new electrochemical hand-held
      device for exhaled NO measurements (NIOX MINO) was compared with a standard
      stationary chemiluminescence unit (NIOX). METHODS: A total of 71 subjects (6-60
      years; 36 males), both healthy controls and atopic patients with and without
      asthma were included. The mean of three approved exhalations (50 ml/s) in each
      device, and the first approved measurement in the hand-held device, were compared
      with regard to NO readings (Bland-Altman plots), measurement feasibility (success
      rate with 6 attempts) and repeatability (intrasubject SD). RESULTS: Success rate
      was high (> or = 84%) in both devices for both adults and children. The subjects
      represented a FENO range of 8-147 parts per billion (ppb). When comparing the
      mean of three measurements (n = 61), the median of the intrasubject difference in
      exhaled NO for the two devices was -1.2 ppb; thus generally the hand-held device
      gave slightly higher readings. The Bland-Altman plot shows that the 95% limits of
      agreement were -9.8 and 8.0 ppb. The intrasubject median difference between the
      NIOX and the first approved measurement in the NIOX MINO was -2.0 ppb, and limits
      of agreement were -13.2 and 10.2 ppb. The median repeatability for NIOX and NIOX
      MINO were 1.1 and 1.2 ppb, respectively. CONCLUSION: The hand-held device (NIOX
      MINO) and the stationary system (NIOX) are in clinically acceptable agreement
      both when the mean of three measurements and the first approved measurement (NIOX
      MINO) is used. The hand-held device shows good repeatability, and it can be used
      successfully on adults and most children. The new hand-held device will enable
      the introduction of exhaled NO measurements into the primary health care.

PMID- 16626493
TI  - Mutacin H-29B is identical to mutacin II (J-T8).
AB  - BACKGROUND: Streptococcus mutans produces bacteriocins named mutacins. Studies of
      mutacins have always been hampered by the difficulties in obtaining active liquid
      preparations of these substances. Some of them were found to be lantibiotics,
      defined as bacterial ribosomally synthesised lanthionine-containing peptides with
      antimicrobial activity. The goal of this study was to produce and characterize a
      new mutacin from S. mutans strain 29B, as it shows a promising activity spectrum
      against current human pathogens. RESULTS: Mutacin H-29B, produced by S. mutans
      strain 29B, was purified by successive hydrophobic chromatography from a liquid
      preparation consisting of cheese whey permeate (6% w/v) supplemented with yeast
      extract (2%) and CaCO3 (1%). Edman degradation revealed 24 amino acids identical
      to those of mutacin II (also known as J-T8). The molecular mass of the purified
      peptide was evaluated at 3246.08 +/- 0.1 Da by MALDI-TOF MS. CONCLUSION: A simple
      procedure for production and purification of mutacins along with its
      characterization is presented. Our results show that the amino acid sequence of
      mutacin H-29B is identical to the already known mutacin II (J-T8) over the first
      24 residues. S. mutans strains of widely different origins may thus produce very
      similar bacteriocins.

PMID- 16626494
TI  - A high-throughput method for quantifying alleles and haplotypes of the malaria
      vaccine candidate Plasmodium falciparum merozoite surface protein-1 19 kDa.
AB  - BACKGROUND: Malaria vaccine efficacy may be compromised if the frequency of non
      target alleles increases following vaccination with a genetically polymorphic
      target. Methods are needed to monitor genetic diversity in polymorphic vaccine
      antigens, but determining which genetic variants of such antigens are present in
      infected individuals is complicated by the frequent occurrence of mixed
      infections. METHODS: Pyrosequencing was used to determine allele frequencies at
      each of six single nucleotide polymorphisms in the Plasmodium falciparum blood
      stage vaccine antigen merozoite surface protein 1 19 kDa (MSP-119) in field
      samples from a vaccine-testing site in Mali. Mixtures of MSP-119 clones were
      created to validate a haplotype-estimating algorithm that uses maximum likelihood
      methods to determine the most probable combination of haplotypes given the allele
      frequencies for an infection and the haplotypes known to be circulating in the
      population. RESULTS: Fourteen unique MSP-119 haplotypes were identified among 351
      genotyped infections. After adjustment to a standard curve, Pyrosequencing
      provided accurate and precise estimates of allele frequencies in mixed
      infections. The haplotype-estimating algorithm provided accurate estimates of
      haplotypes in mixed infections containing up to three haplotypes. Based on the
      MSP-119 locus, approximately 90% of the 351 infections contained two or fewer
      haplotypes. CONCLUSION: Pyrosequencing in conjunction with a haplotype-estimating
      algorithm provides accurate estimates of haplotypes present in infections with up
      to 3 haplotypes, and can be used to monitor genetic diversity in parasite
      populations prior to and following introduction of MSP-1-based malaria vaccines.

PMID- 16626495
TI  - Cataract surgery by appointment--a pilot study.
AB  - BACKGROUND: "Cataract Surgery by Appointment" is a new method of delivery of
      cataract surgery that reduces the time a patient spends in hospital by their
      direct arrival at the operating theatre, having self-prepared for surgery, thus
      avoiding admission to the ward or time spent in the Day Case Unit. The patient
      can stay as little as 20 minutes from their arrival to going home. We describe
      the process in detail, and seek to evaluate the visual outcome, safety and
      patient satisfaction of same. METHODS: Visual outcome and safety data were
      obtained from patients' medical records, prospectively. Patients were also
      surveyed by a questionnaire to determine their satisfaction with the service and
      viability as a prospect for providing a more efficient cataract surgery service.
      RESULTS: In 2002, fifty-one eyes of 39 consecutive patients underwent "Cataract
      Surgery by Appointment". There were 16 male and 23 female. The pre-operative best
      corrected visual acuity was 6/9 or better in 17 (33%) eyes. The post-operative
      best-corrected visual acuity was 6/9 or better in 44 (86%) eyes. There were no
      per-operative complications. Post-operative complications occurred in 3 (6%)
      eyes. The average number of days from surgery to final discharge was 14.5 days.
      Twenty-eight (72%) completed questionnaires were returned. The results show that
      the majority of patients were satisfied with their overall experience of this
      mode of delivery for cataract surgery. CONCLUSION: "Cataract Surgery by
      Appointment" performed under local anaesthesia by a skilled ophthalmic surgeon
      appears to be safe and effective for highly selected cases. This method of
      delivery gave a high level of patient satisfaction, and is the ultimate form of
      day case cataract surgery. The method may gain widespread use should per
      operative intracameral pupil dilatation prove to be effective and acceptable.
      Attention should be paid to risk-stratification, so complex cases are allocated
      more time on the operating list.

PMID- 16626496
TI  - Transcription profiles of non-immortalized breast cancer cell lines.
AB  - BACKGROUND: Searches for differentially expressed genes in tumours have made
      extensive use of array technology. Most samples have been obtained from tumour
      biopsies or from established tumour-derived cell lines. Here we compare cultures
      of non-immortalized breast cancer cells, normal non-immortalized breast cells and
      immortalized normal and breast cancer cells to identify which elements of a
      defined set of well-known cancer-related genes are differentially expressed.
      METHODS: Cultures of cells from pleural effusions or ascitic fluids from breast
      cancer patients (MSSMs) were used in addition to commercially-available normal
      breast epithelial cells (HMECs), established breast cancer cell lines (T-est) and
      established normal breast cells (N-est). The Atlas Human Cancer 1.2 cDNA
      expression array was employed. The data obtained were analysed using widely
      available statistical and clustering software and further validated through real
      time PCR. RESULTS: According to Significance Analysis of Microarray (SAM) and
      AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities
      between HMECs and MSSMs (p < 0.01). Some of these genes have already been
      directly linked with breast cancer, metastasis and malignant progression, whilst
      others encode receptors linked to signal transduction pathways or are otherwise
      related to cell proliferation. Fifty genes showed at least a 2.5-fold difference
      between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM.
      Most of these classified as genes related to metabolism and cell communication.
      CONCLUSION: The expression profiles of 1176 genes were determined in finite life
      span cultures of metastatic breast cancer cells and of normal breast cells.
      Significant differences were detected between the finite life-span breast cancer
      cell cultures and the established breast cancer cell lines. These data suggest
      caution in extrapolating information from established lines for application to
      clinical cancer research.

PMID- 16626497
TI  - The statistics of identifying differentially expressed genes in Expresso and TM4:
      a comparison.
AB  - BACKGROUND: Analysis of DNA microarray data takes as input spot intensity
      measurements from scanner software and returns differential expression of genes
      between two conditions, together with a statistical significance assessment. This
      process typically consists of two steps: data normalization and identification of
      differentially expressed genes through statistical analysis. The Expresso
      microarray experiment management system implements these steps with a two-stage,
      log-linear ANOVA mixed model technique, tailored to individual experimental
      designs. The complement of tools in TM4, on the other hand, is based on a number
      of preset design choices that limit its flexibility. In the TM4 microarray
      analysis suite, normalization, filter, and analysis methods form an analysis
      pipeline. TM4 computes integrated intensity values (IIV) from the average
      intensities and spot pixel counts returned by the scanner software as input to
      its normalization steps. By contrast, Expresso can use either IIV data or median
      intensity values (MIV). Here, we compare Expresso and TM4 analysis of two
      experiments and assess the results against qRT-PCR data. RESULTS: The Expresso
      analysis using MIV data consistently identifies more genes as differentially
      expressed, when compared to Expresso analysis with IIV data. The typical TM4
      normalization and filtering pipeline corrects systematic intensity-specific bias
      on a per microarray basis. Subsequent statistical analysis with Expresso or a TM4
      t-test can effectively identify differentially expressed genes. The best
      agreement with qRT-PCR data is obtained through the use of Expresso analysis and
      MIV data. CONCLUSION: The results of this research are of practical value to
      biologists who analyze microarray data sets. The TM4 normalization and filtering
      pipeline corrects microarray-specific systematic bias and complements the
      normalization stage in Expresso analysis. The results of Expresso using MIV data
      have the best agreement with qRT-PCR results. In one experiment, MIV is a better
      choice than IIV as input to data normalization and statistical analysis methods,
      as it yields as greater number of statistically significant differentially
      expressed genes; TM4 does not support the choice of MIV input data. Overall, the
      more flexible and extensive statistical models of Expresso achieve more accurate
      analytical results, when judged by the yardstick of qRT-PCR data, in the context
      of an experimental design of modest complexity.

PMID- 16626498
TI  - The effect of pre-pregnancy body mass index and gestational weight gain on
      pregnancy outcomes in urban care settings in Urmia-Iran.
AB  - BACKGROUND: Nutritional status of women has been considered an important
      prognostic indicator of pregnancy outcomes. Few studies have evaluated patterns
      of weight gain and pre-pregnancy body mass index in developing regions where
      malnutrition and poor weight gain as well as maternal obesity have significant
      influences on the pregnancy outcome. This study aims to show effect of pregnancy
      body mass index and the corresponding gestational weight gain on the outcome of
      pregnancy. METHODS: On a prospective cross sectional study, two hundred and
      seventy women from urban areas of Northwest Iran were recruited for participation
      during their first eight weeks of pregnancy. Body mass index (BMI) was
      categorized and gestational weight gain was divided into two groups of normal and
      abnormal based on recommendations of Institute of Medicine (IOM) published in
      1990. Chi square and one way ANOVA were used in the univariate analysis of the
      association between weight gain and corresponding adverse outcomes including
      cesarean, preterm labor and low neonatal birth weight. Adjusted odds ratios for
      adverse outcomes were determined by multiple logistic regression models, while
      controlling for the following factors: maternal age, parity, and education.
      RESULTS: Both pre-pregnancy BMI < 19 and abnormal weight gain during pregnancy
      were found to be associated with low neonatal birth weight defined as < 2500 g.
      Abnormal weight gain, during pregnancy was not related to an increased risk of
      preterm labor or cesarean delivery but it was highly associated with low birth
      weight (LBW)(P < 0.05). CONCLUSION: Low pre-pregnancy BMI is an established risk
      factor for LBW. Abnormal gestational weight gain may further complicate the
      pregnancy as an additional risk factor for neonatal LBW. All women, regardless of
      their pre-pregnancy BMI may be at risk for abnormal weight gain and hence low
      birth weight. Pre-pregnancy and gestation nutritional assessments remain
      significant part of all prenatal visits.

PMID- 16626499
TI  - Measuring social capital in a known disadvantaged urban community--health policy
      implications.
AB  - BACKGROUND: To assess the social capital profile of a known disadvantaged area a
      large cross-sectional survey was undertaken. The social capital profile of this
      area was compared to data from the whole of the state. The overall health status
      of the disadvantaged area was assessed in relation to a wide variety of social
      capital related variables. Univariate and multivariate analysis were undertaken.
      RESULTS: In the univariate analysis many statistically significant differences
      were found between the respondents in the disadvantaged area and the state
      estimates including overall health status, perceived attributes of the
      neighbourhood, levels of trust, community involvement and social activities. In
      the multivariate analysis very few variables were found to be statistically
      significantly associated with poorer health status. The variables that jointly
      predicted poorer health status in the disadvantaged area were older age, lower
      income, low sport participation, non-seeking help from neighbours and non
      attendance at public meetings. CONCLUSION: Measuring social capital on a
      population level is complex and the use of epidemiologically-based population
      surveys does not produce overly valuable results. The inter-relational/dependence
      dichotomy of social capital is not yet fully understood making meaningful
      measurement in the broader population extremely difficult and hence is of
      questionable value for policy decision making.

PMID- 16626500
TI  - In silico identification and comparative analysis of differentially expressed
      genes in human and mouse tissues.
AB  - BACKGROUND: Screening for differentially expressed genes on the genomic scale and
      comparative analysis of the expression profiles of orthologous genes between
      species to study gene function and regulation are becoming increasingly feasible.
      Expressed sequence tags (ESTs) are an excellent source of data for such studies
      using bioinformatic approaches because of the rich libraries and tremendous
      amount of data now available in the public domain. However, any large-scale EST
      based bioinformatics analysis must deal with the heterogeneous, and often
      ambiguous, tissue and organ terms used to describe EST libraries. RESULTS: To
      deal with the issue of tissue source, in this work, we carefully screened and
      organized more than 8 million human and mouse ESTs into 157 human and 108 mouse
      tissue/organ categories, to which we applied an established statistic test using
      different thresholds of the p value to identify genes differentially expressed in
      different tissues. Further analysis of the tissue distribution and level of
      expression of human and mouse orthologous genes showed that tissue-specific
      orthologs tended to have more similar expression patterns than those lacking
      significant tissue specificity. On the other hand, a number of orthologs were
      found to have significant disparity in their expression profiles, hinting at
      novel functions, divergent regulation, or new ortholog relationships. CONCLUSION:
      Comprehensive statistics on the tissue-specific expression of human and mouse
      genes were obtained in this very large-scale, EST-based analysis. These
      statistical results have been organized into a database, freely accessible at our
      website http://gln.ibms.sinica.edu.tw/product/HMDEG/EST/index.php, for easy
      searching of human and mouse tissue-specific genes and for investigating gene
      expression profiles in the context of comparative genomics. Comparative analysis
      showed that, although highly tissue-specific genes tend to exhibit similar
      expression profiles in human and mouse, there are significant exceptions,
      indicating that orthologous genes, while sharing basic genomic properties, could
      result in distinct phenotypes.

PMID- 16626501
TI  - Classification and risk stratification of invasive breast carcinomas using a real
      time quantitative RT-PCR assay.
AB  - INTRODUCTION: Predicting the clinical course of breast cancer is often difficult
      because it is a diverse disease comprised of many biological subtypes. Gene
      expression profiling by microarray analysis has identified breast cancer
      signatures that are important for prognosis and treatment. In the current
      article, we use microarray analysis and a real-time quantitative reverse
      transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological
      'intrinsic' subtypes and proliferation. METHODS: Gene sets were selected from
      microarray data to assess proliferation and to classify breast cancers into four
      different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and
      Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas,
      one fibroadenoma and five normal tissues) and three breast cancer cell lines were
      prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised
      of 53 genes. Biological subtypes were assigned from the microarray and qRT-PCR
      data by hierarchical clustering. A proliferation signature was used as a single
      meta-gene (log2 average of 14 genes) to predict outcome within the context of
      estrogen receptor status and biological 'intrinsic' subtype. RESULTS: We found
      that the qRT-PCR assay could determine the intrinsic subtype (93% concordance
      with microarray-based assignments) and that the intrinsic subtypes were
      predictive of outcome. The proliferation meta-gene provided additional prognostic
      information for patients with the Luminal subtype (P = 0.0012), and for patients
      with estrogen receptor-positive tumors (P = 3.4 x 10-6). High proliferation in
      the Luminal subtype conferred a 19-fold relative risk of relapse (confidence
      interval = 95%) compared with Luminal tumors with low proliferation. CONCLUSION:
      A real-time qRT-PCR assay can recapitulate microarray classifications of breast
      cancer and can risk-stratify patients using the intrinsic subtype and
      proliferation. The proliferation meta-gene offers an objective and quantitative
      measurement for grade and adds significant prognostic information to the
      biological subtypes.

PMID- 16626502
TI  - A classification based framework for quantitative description of large-scale
      microarray data.
AB  - Genome-wide surveys of transcription depend on gene classifications for the
      purpose of data interpretation. We propose a new information-theoretical-based
      method to: assess significance of co-expression within any gene group;
      quantitatively describe condition-specific gene-class activity; and
      systematically evaluate conditions in terms of gene-class activity. We applied
      this technique to describe microarray data tracking Escherichia coli
      transcriptional responses to more than 30 chemical and physiological
      perturbations. We correlated the nature and breadth of the responses with the
      nature of perturbation, identified gene group proxies for the perturbation
      classes and quantitatively compared closely related physiological conditions.

PMID- 16626503
TI  - Intensive care acquired infection is an independent risk factor for hospital
      mortality: a prospective cohort study.
AB  - INTRODUCTION: The aim of this study was to elucidate the impact of intensive care
      unit (ICU)-acquired infection on hospital mortality. METHODS: Patients with a
      longer than 48 hour stay in a mixed 10 bed ICU in a tertiary-level teaching
      hospital were prospectively enrolled between May 2002 and June 2003. Risk factors
      for hospital mortality were analyzed with a logistic regression model. RESULTS:
      Of 335 patients, 80 developed ICU-acquired infection. Among the patients with ICU
      acquired infections, hospital mortality was always higher, regardless of whether
      or not the patients had had infection on admission (infection on admission group
      (IAG), 35.6% versus 17%, p = 0.008; and no-IAG, 25.7% versus 6.1%, p = 0.023). In
      IAG (n = 251), hospital stay was also longer in the presence of ICU-acquired
      infection (median 31 versus 16 days, p < 0.001), whereas in no-IAG (n = 84),
      hospital stay was almost identical with and without the presence of ICU-acquired
      infection (18 versus 17 days). In univariate analysis, the significant risk
      factors for hospital mortality were: Acute Physiology and Chronic Health
      Evaluation (APACHE) II score >20, sequential organ failure assessment (SOFA)
      score >8, ICU-acquired infection, age > or = 65, community-acquired pneumonia,
      malignancy or immunosuppressive medication, and ICU length of stay >5 days. In
      multivariate logistic regression analysis, ICU-acquired infection remained an
      independent risk factor for hospital mortality after adjustment for APACHE II
      score and age (odds ratio (OR) 4.0 (95% confidence interval (CI): 2.0-7.9)) and
      SOFA score and age (OR 2.7 (95% CI: 2.9-7.6)). CONCLUSION: ICU-acquired infection
      was an independent risk factor for hospital mortality even after adjustment for
      the APACHE II or SOFA scores and age.

PMID- 16626504
TI  - The fragile X syndrome: exploring its molecular basis and seeking a treatment.
AB  - Fragile X syndrome (FXS) - the leading cause of inherited mental retardation - is
      an X-linked disease caused by loss of expression of the FMR1 (fragile X mental
      retardation 1) gene. In addition to impairment of higher-cognitive functions, FXS
      patients show a variety of physical and other mental abnormalities. FMRP, the
      protein encoded by the FMR1 gene, is thought to play a key role in translation,
      trafficking and targeting of mRNA in neurons. To better understand FMRP's
      functions, the protein partners and mRNA targets that interact with FMRP have
      been sought. These and functional studies have revealed links with processes such
      as cytoskeleton remodelling via the RhoGTPase pathway and mRNA processing via the
      RNA interference pathway. In this review, we focus on recent insights into the
      function of FMRP and speculate on how the absence of FMRP might cause the
      clinical phenotypes seen in FXS patients. Finally, we explore potential therapies
      for FXS.

PMID- 16626505
TI  - Mutation trend of hemagglutinin of influenza A virus: a review from a
      computational mutation viewpoint.
AB  - Since 1999 we have developed two computational mutation approaches to analyze the
      protein primary structure whose methodology and implications were reviewed in
      2002. Our first approach is the calculation of predictable and unpredictable
      portions of amino-acid pairs in a protein, and the second is the calculation of
      amino-acid distribution rank in a protein. Both approaches provide quantitative
      measures to present a protein, which we have used to study a number of proteins
      with numerous mutations such as p53 proteins. More recently, we focussed our
      efforts on analyzing the proteins mutating frequently over time such as
      hemagglutinins of influenza A viruses. In this review we summarise our findings
      and their implications for hemagglutinin mutations in combination with some newly
      available data. Our approaches throw light on the true nature of genetic
      heterogeneity of influenza virus hemagglutinins; that is, the protein variability
      is highly relevant to its amino-acid construction. Using these approaches, we can
      monitor new mutations from influenza virus hemagglutinins and may predict their
      mutations in the future.

PMID- 16626506
TI  - Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury
      induced by isoproterenol in rats.
AB  - AIM: To determine the cardioprotective action of ghrelin and des-octanoyl ghrelin
      in rats with isoproterenol-induced myocardial injury. METHODS: Rats were
      subcutaneously injected with isoproterenol (ISO; 20, 10, and 5 mg/kg) on d 1, 2
      and 3, respectively, and then 3 mg/kg for the next 7 d with or without ghrelin or
      des-octanoyl-ghrelin (100 microg/kg, twice daily). Plasma ghrelin and growth
      hormone levels were assayed using radioimmunoassay methods. Growth hormone
      secretagogue receptor (GHSR) and ghrelin mRNA were determined using RT-PCR. The
      maximal binding capacity and the affinity for [3H]ghrelin were determined by
      receptor binding assays. RESULTS: Compared with controls, ISO-treated rats showed
      severe myocardial injury, cardiomegaly, infarction-like necrosis and massive
      fibrosis with increases in irradiated-ghrelin (ir-ghrelin) content in plasma by
      67% and myocardia by 66% and in the mRNA level in the myocardia by 93% (P<0.01).
      ISO-treated rats had 95% (P<0.01) higher GHSR mRNA levels in the myocardia. The
      maximal binding capacity of [3H]ghrelin for myocardial sarcolemma was higher in
      ISO-treated rats than in controls. Ghrelin administration improved cardiac
      function and ameliorated cardiomegaly and attenuated myocardial lipid
      peroxidation injury and relieved cardiac fibrosis as compared with ISO treatment
      alone. Administration of des-octanoyl ghrelin effectively antagonized ISO-induced
      myocardial injury and improved all parameters measured. However, the therapeutic
      effect of des-octanoyl ghrelin was significantly weaker than that of ghrelin. The
      plasma growth hormone level increased markedly, by 1.5-fold (P<0.01), with
      ghrelin administration as compared with that in controls, but was unaltered in
      des-octanoyl ghrelin group. CONCLUSION: Myocardial ghrelin and GHSR were up
      regulated during ISO-induced myocardial injury. The protective effect of ghrelin
      against ISO-induced cardiac function injury and fibrosis was more potent than
      that of des-octanoyl ghrelin, which suggests that ghrelin could be an endogenous
      cardioprotective factor in ischemic heart disease, and that its effects include
      growth hormone-dependent and -independent pathways.

PMID- 16626507
TI  - Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in
      normal and high-glucose environments.
AB  - AIM: Ginkgo biloba extract is a natural product used widely for cerebral and
      cardiovascular diseases. It is mainly composed of terpene lactones (ginkgolide A
      and B) and flavone glycosides (eg quercetin and kaempferol). To better understand
      the cardiac electromechanical action of Ginkgo biloba extract in normal and
      diabetic states, this study was designed to examine the effect of ginkgolide B on
      cardiomyocyte contractile function under normal and high-glucose environments.
      METHODS: Isolated adult rat ventricular myocytes were cultured for 6 h in a serum
      free medium containing either normal (NG; 5.5 mmol/L) or high (HG; 25.5 mmol/L)
      glucose with or without ginkgolide B (0.5-2.0 microg/mL). Mechanical properties
      were evaluated using the IonOptix MyoCam system. Contractile properties analyzed
      included peak shortening (PS), maximal velocity of shortening/relengthening (+/
      dl/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Levels of
      essential Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase
      (SERCA2a), phospholamban (PLB) and Na(+)-Ca(2+) exchanger (NCX) were assessed by
      Western blotting. RESULTS: Ginkgolide B nullified HG-induced prolongation in
      TR90. However, ginkgolide B depressed PS, +/-dl/dt and shortened TPS in NG and HG
      cells. Ginkgolide B also prolonged TR90 in NG cells. Western blot analysis
      revealed that HG upregulated SERCA2a and downregulated PLB expression without
      affecting that of NCX. Ginkgolide B disrupted the NG-HG response pattern in
      SERCA2a and NCX without affecting that of PLB. CONCLUSION: Ginkgolide B affects
      cardiomyocyte contractile function under NG or HG environments in a paradoxical
      manner, which may be attributed to uneven action on Ca(2+) regulatory proteins
      under NG and HG conditions.

PMID- 16626508
TI  - Increased RhoA translocation in aorta of diabetic rats.
AB  - AIM: To analyze RhoA expression and activation in the aorta of diabetic rats.
      METHODS: Male SD rats (n=70) were divided into 2 groups: the diabetic group and
      the control group. Diabetes was induced by intravenous injection of
      streptozotocin (55 mg/kg). The Rats were studied 3 weeks after the induction of
      diabetes. Western blotting was used to measure the expression and activation of
      Rho. RESULTS: Heart rate was measured 24 h/d; it decreased by 58+/-13 beats/min
      in the diabetic rats. Isometric tension showed that the contraction of diabetic
      aorta was significantly reduced compared with that of control aorta when
      stimulated by KCl and serotonin. The relaxation of the diabetic aorta was reduced
      when stimulated by acetylcholine. An enhanced RhoA translocation in the aortic
      tissues of diabetic rats was determined by a 90% increase in membrane-bound RhoA,
      indicating that the activation of RhoA is markedly increased in the diabetic
      aorta. CONCLUSION: Our data suggest that upregulated RhoA could be involved in
      the vascular dysfunction of diabetic rats.

PMID- 16626509
TI  - Prostaglandin A1 inhibits increases in intracellular calcium concentration,
      TXA(2) production and platelet activation.
AB  - AIM: In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1)
      had neuroprotective effects in a rodent ischemic model. In the present study we
      aimed to investigate the inhibitory effect of PGA1 on platelet function. METHOD:
      The rate of aggregation of human platelets was measured by using turbidimetry.
      The rate of adhesion of platelets to cultured endothelial cells was determined by
      using [(3)H]-adenine labeled platelets. 5-Hydroxytryptamine release from
      platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The
      levels of TXB(2), a stable metabolite of TXA(2), were determined by radioimmuno
      assay. Alternations in platelet morphology were observed using an electron
      microscope, and the intraplatelet free calcium concentrations were measured with
      Fluo-3/AM FCM assay. RESULTS: PGA1 significantly inhibited thrombin-, collagen-
      and ADP-induced aggregation and adhesion of platelets. The morphological changes
      of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release
      of 5-hydroxytyptamine from dense granules and the synthesis of TXA(2).
      CONCLUSION: PGA1 inhibits the activation of platelets probably through blocking
      increases in intracellular calcium concentration and TXA(2) synthesis.

PMID- 16626510
TI  - Induction of collateral artery growth and improvement of post-infarct heart
      function by hepatocyte growth factor gene transfer.
AB  - AIM: To study the effect of adenovirus5-mediated human hepatocyte growth factor
      (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model. METHODS:
      Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF
      group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior
      descending coronary artery (LAD) ligation, Ad5-HGF was transferred into the
      myocardium via the right coronary artery. Coronary angiography and gated cardiac
      perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation,
      respectively, to evaluate collateral artery growth and cardiac perfusion. Then
      all animals were killed, the expression of HGF and alpha-smooth muscle actin
      (alpha-SMA) were evaluated by enzyme-linked immunosorbent assay and
      immunohistochemistry. RESULTS: Compared with the null-Ad(5) group, higher
      expression of human HGF was observed in the myocardium in the Ad(5)-HGF group
      (109.3+/-7.8 vs 6.2+/-2.6, t=30.685, P<0.01). The left ventricular ejection
      fraction was higher in the Ad(5)-HGF group than in the null-Ad(5) group (43.9+/
      4.3 vs 30.4+/-2.8, t=6.514, P<0.01). From the 4th week to the 7th week after
      operation, left ventricular end systolic volume (42.1+/-3.0 vs 31.0+/-4.9,
      t=12.800, P<0.01) and left ventricular end diastolic volume (62.2+/-4.2 vs 55.0+/
      4.8 t=13.207, P<0.01) were improved in the Ad(5)-HGF group. Cardiac perfusion was
      significantly improved in the Ad(5)-HGF group. In the Ad(5)-HGF group, growth of
      collateral arteries was obviously greater (average rank sum 9.17 vs 3.83, n=6, u=
      2.687, P<0.01), and the number of alpha-SMA(+) vessels/mm(2) was significantly
      greater (56.1+/-4.2 vs 16.4+/-3.5, t=17.731, P<0.01) than in the null-Ad(5)
      group. CONCLUSION: High expression levels of human HGF were observed in the
      myocardium because of non-infarct-related vessel transfer. HGF can increase the
      number of functional arterioles and improve collateral artery growth. HGF can
      improve cardiac perfusion and heart function.

PMID- 16626511
TI  - Antisense oligonucleotides-induced local blockade of T-bet expression leads to
      airway inflammation in rats.
AB  - AIM: To explore whether local blockade of T-box expressed in T cells (T-bet)
      expression in the lungs could lead to airway inflammation. METHODS: Twenty-four
      rats were randomly divided into 4 groups: saline group, ovalbumin (OVA)
      sensitized group, nonsense group, and the antisense group. The OVA-sensitized
      rats were sensitized and challenged with OVA, and the rats in the nonsense and
      antisense groups were subjected to an aerosol delivery of the nonsense and
      antisense oligonucleotides (AS-ODN) of T-bet (0.1%, w/v). The levels of
      interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-5 in the
      bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the mRNA and the
      protein expression of T-bet and GATA-3 genes were examined by in situ
      hybridization and Western blot analysis, respectively. RESULTS: The expression of
      T-bet mRNA and protein in the lungs of the rats in the antisense group were
      inhibited effectively. The lungs of the rats in the antisense and OVA-sensitized
      groups showed eosinophil and lymphocyte inflammatory infiltration, and
      eosinophilia located predominantly around the airways. The number of GATA-3 mRNA
      positive cells and the level of GATA-3 protein in the lungs of the rats in the
      antisense and the OVA-sensitized groups significantly increased. The level of IL
      4 and IL-5 in the BALF in the antisense and OVA-sensitized groups were elevated,
      but the level of IFN-gamma decreased markedly. CONCLUSION: Antisense ODN-induced
      local blockade of T-bet expression leads to airway inflammation with a selective
      alteration in patterns of cytokine expression and recruitment of eosinophil cells
      similar to that in the OVA-sensitized animals.

PMID- 16626512
TI  - Proteomic analysis of differential protein expression in early process of
      pancreatic regeneration in pancreatectomized rats.
AB  - AIM: A broad-range proteomic approach was applied to investigate the complexity
      of the mechanisms involved in pancreatic regeneration for identification of new
      targets of diabetes treatment and potential markers of pancreatic stem cells.
      METHODS: A regeneration pancreatic model was induced by 90% partial
      pancreatectomy (Px) in rats. Changes in the protein expression in regenerating
      rat pancreas on the third day after Px, as compared with rats that received sham
      surgery, were analyzed by using 2-D gel electrophoresis (2-DE), mass spectrometry
      (MS), and mass fingerprinting. RESULTS: 2-DE revealed 91 spots with at least 1.5
      fold increases in expression at 3 d after pancreatectomy and 53 differentially
      expressed proteins that were identified by peptide mass fingerprinting (PMF).
      These included cell growth-related, lipid and energy metabolism-related, protein
      and amino acid metabolism-related proteins, and signal transduction proteins.
      Vimentin, CK8, L-plastin, hnRNP A2/B1, and AGAT are associated with embryogenesis
      and cell differentiation, and may be new potential pancreatic stem cells markers.
      CONCLUSION: The proteome profiling technique provided a broad-based and effective
      approach for the rapid assimilation and identification of adaptive protein
      changes during pancreas regeneration induced by pancreatectomy. Our data clarify
      the global proteome during the pancreatic proliferation and differentiation
      processes, which is important for better understanding of pancreatic regeneration
      and for discovering of protein biomarkers for pancreatic stem cells.

PMID- 16626513
TI  - Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in
      rats with daunorubicin-induced nephrosis.
AB  - AIM: To study the potential pathological role of endogenous angiopoietins in
      daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy
      male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or
      a control group (n=30). The rats in the DRB group were injected with DRB (15
      mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12
      weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary
      protein quantitative measurements (24 h UPQM), and determination of plasma tumor
      necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2
      (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic
      Acid Schiff (PAS) staining, immunohistochemical staining and in situ
      hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the
      DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and
      expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased.
      Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with
      24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM).
      In comparison, expression of Ang2 mRNA and protein in glomeruli were positively
      correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there
      was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha
      and expression of TNF-alpha in glomeruli were positively correlated with
      expression of Ang2 mRNA and protein in glomeruli. There was a negative
      correlation between Ang1 protein expression and Ang2 protein expression in
      glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led
      to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in
      plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2
      in both plasma and glomeruli may mediate protein permeability through the
      glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate
      the progress of glomerulosclerosis by upregulating a component expression of
      extracellular matrix.

PMID- 16626514
TI  - Role of 11-beta-hydroxysteroid dehydrogenase type 1 in differentiation of 3T3-L1
      cells and in rats with diet-induced obesity.
AB  - AIM: To observe the roles of 11-beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) in in vitro preadipocyte differentiation and in rats with diet-induced
      obesity (DIO). METHODS: Protein expression of 11beta-HSD1 in the process of 3T3
      L1 cell differentiation and in various tissues of the rats were detected by
      Western blot analysis; expression of 11beta-HSD1 mRNA and glucocorticoid receptor
      (GR) and other marker genes of preadipocyte differentiation were detected by
      using real-time PCR. RESULTS: Lipid droplets in 3T3-L1 cells accumulated and
      increased after stimulation. A dramatically elevated protein level of 11beta
      HSD1, especially in the late stages of 3T3-L1 cell differentiation, was detected.
      The relative mRNA levels of 11beta-HSD1, GR and cell differentiation markers LPL,
      aP2, and FAS were upregulated, and Pref-1 was downregulated during the
      differentiation. In DIO rats, bodyweight, visceral adipose mass index and the
      protein expression of 11beta-HSD1 increased, especially in adipose tissue, brain
      and muscles. Serum insulin, triglyceride, total cholesterol and low-density
      lipoprotein cholesterol were found to be increased in DIO rats, but without any
      obvious changes in blood glucose or tumor necrosis factor-alpha levels.
      CONCLUSION: 11beta-HSD1 may promote preadipocyte differentiation, and may be
      involved in the development of obesity.

PMID- 16626515
TI  - Synthesis and anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoro
      methanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid.
AB  - AIM: To synthesize and study the anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2
      (4-trifluoromethanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid (compound
      I). METHODS: Compound I was prepared in 6 steps, using 4-(2-hydroxy-ethyl)-phenol
      as the starting material. The in vitro selectivity and potency of target compound
      I, rosiglitazone and WY-14643 on human PPARalpha and PPARgamma were determined in
      reporter gene assays. In vivo, rosiglitazone and compound I were administered
      orally to KK(Ay) mice for 14 d. Insulin tolerance tests and oral glucose
      tolerance tests were performed on the 10th and 14th day of treatment,
      respectively. At the end of the treatment, sera were collected for biochemical
      analysis. RESULTS: In vitro, compound I significantly activated both PPARalpha
      and PPARgamma. In vivo, compound I corrected the impaired insulin and glucose
      tolerance of KK(Ay) mice, and produced a significant reduction in plasma
      triglyceride levels after 14 d of treatment. The effect produced was significant
      compared with the control group. CONCLUSION: Both in vitro and in vivo anti
      diabetic activity studies for compound I were conducted and the data suggest that
      this compound is a potentially effective anti-diabetic agent.

PMID- 16626516
TI  - Sulfasalazine prevents apoptosis in spermatogenic cells after experimental
      testicular torsion/detorsion.
AB  - AIM: To determine whether sulfasalazine can prevent apoptosis in spermatogenic
      cells by preventing the activation of NF-kappaB in spermatogenic epithelium in
      experimental testicular torsion. METHODS: Thirty-two adult male Sprague-Dawley
      rats were subjected to unilateral 720 degree testicular torsion for durations of
      0 h and 2 h, then the torsion was relieved. The ischemic/reperfused testes were
      collected for the detection of NF-kappaB expression with Western blotting and
      immunohistochemistry techniques, and detection of apoptosis with TUNEL
      techniques. RESULTS: The NF-kappaB coefficient of spermatogenic epithelium and
      the apoptosis index of spermatogenic cells were significantly different in the
      operation and the sham-operation groups after experimental testicular torsion
      (P<0.01). CONCLUSION: NF-kappaB activation of spermatogenic epithelium is related
      to apoptosis of spermatogenic cells. Sulfasalazine can prevent apoptosis in
      spermatogenic cells after the experimental testicular torsion through prevention
      of NF-kappaB activation.

PMID- 16626517
TI  - Effects of adenoviral gene transfer of mutated IkappaBalpha, a novel inhibitor of
      NF-kappaB, on human monocyte-derived dendritic cells.
AB  - AIM: To investigate the effects of adenoviral gene transfer of IkappaBalpha
      mutant (IkappaBalphaM), a novel inhibitor of nuclear factor kappaB (NF-kappaB),
      on apoptosis, phenotype and function of human monocyte-derived dendritic cells
      (DC). METHODS: Monocytes, cocultured with granulocyte/macrophage colony
      stimulating factor (GM-CSF; 900 ng/mL) and interleukin (IL)-4 (300 ng/mL) for 5
      d, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 2 d
      differentiated into mature DC. Monocytes were either left untransfected or were
      transfected with AdIkappaBalphaM or AdLacZ. The transcription and expression of
      the IkappaBalphaM gene, and the inhibitory effect of IkappaBalphaM on tumor
      necrosis factor (TNF)-alpha-induced NF-kappaB activation in mature DC were
      detected by polymerase chain reaction (PCR), reverse transcription-polymerase
      chain reaction (RT-PCR), Western blot analysis, and electrophoretic mobility
      shift assays, respectively. The phenotype, apoptosis, IL-12 secretion level of
      DC, and ability to stimulate the proliferation of T cells were determined by flow
      cytometry, enzyme-linked immunosorbent assay and mixed leukocyte reaction.
      RESULTS: PCR and RT-PCR were used to detect a unique 801 bp band in
      AdIkappaBalphaM-transfected mature DC, and also a dose- and time-dependent
      expression of the IkappaBalphaM gene, which peaked at a multiplicity of infection
      of 100 pfu/cell and at 48 h. Furthermore, AdIkappaBalphaM significantly
      suppressed the TNF-alpha-induced NF-kappaB activation, augmented apoptosis,
      downregulated CD80, CD83, and CD86 surface molecules, IL-12 secretion levels and
      the ability to stimulate the proliferation of T cells in mature DC. CONCLUSION:
      AdIkappaBalphaM effectively transfected and potently inhibited NF-kappaB
      activation in monocyte-derived mature DC. Overexpression of the IkappaBalphaM
      gene in mature DC may contribute to T-cell immunosuppression through induction of
      DC apoptosis and downregulation of B7 molecules, providing a potential strategy
      for future DC-based immunotherapy of asthma.

PMID- 16626518
TI  - Engagement of PSGL-1 enhances beta(2)-integrin-involved adhesion of neutrophils
      to recombinant ICAM-1.
AB  - AIM: The interactions of selectins and their ligands initiate the process of
      leukocyte migrating into inflamed tissue. P-selectin glycoprotein ligand 1 (PSGL
      1) is the best characterized ligand of selectins, and has been demonstrated to
      mediate the adhesion of leukocytes to all three selectins in vivo. PSGL-1 not
      only functions as an anchor molecule to capture the leukocytes to the activated
      endothelial cells by its interaction with selectins, but also transduces the
      signals to activate leukocytes. Our present work aimed to investigate the
      mechanism by which PSGL-1-mediated signal activates neutrophils and enhances the
      adhesion to the endothelial cells. METHODS: We detected the effects of the
      engagement of PSGL-1 with monoclonal antibodies (mAb) or P-selectin on the
      adhesion of neutrophils to the recombinant intercellular adhesion molecule-1
      (ICAM-1), and on the expression of beta(2)-integrin. Additionally, the role of
      cytoskeleton in these process was studied by using inhibitor cytochalasin B.
      RESULTS: The engagement of PSGL-1 increased the expression of beta(2)-integrin on
      the surface of neutrophils and enhanced the adhesion of neutrophils to the
      recombinant ICAM-1. mAb against CD18 impaired the adhesion of PSGL-1-engaged
      neutrophils to ICAM-1. Moreover, the inhibitor cytochalasin B largely blocked the
      increase of CD18 expression as well as the adhesion of PSGL-1-engaged neutrophils
      to ICAM-1. CONCLUSION: The PSGL-1-transduced signals can enhance beta(2)-integrin
      involved adhesion of neutrophils to the recombinant ICAM-1, and this process
      depends on the dynamics of cytoskeleton.

PMID- 16626519
TI  - Biosynthesis of imipramine glucuronide and characterization of imipramine
      glucuronidation catalyzed by recombinant UGT1A4.
AB  - AIM: To study the profile of imipramine N+-glucuronidation using homogenates of
      recombinant uridine-5'-diphosphoglucuronosyltransferase 1A4 (UGT1A4) from
      baculovirus-infected sf9 cells. METHODS: Recombinant UGT1A4 was obtained from sf9
      cells infected with recombinant baculovirus. Imipramine N(+)-glucuronide was
      biosynthesized by incubating imipramine with recombinant UGT1A4 and then purified
      with solid-phase cartridges. A reversed phase-high pressure liquid chromatography
      (RP-HPLC) assay method was used to directly measure the concentration of
      imipramine and its metabolite, imipramine N(+)-glucuronide, with p-nitrophenol as
      the internal standard. The validated method was used to characterize the activity
      of recombinant UGT1A4 and carry out kinetic studies on imipramine glucuronidation
      in vitro. RESULTS: The high concentration of imipramine inhibited glucuronide
      conjugation, so the formula V=V(max).S/(Km+S+S(2)/K(i)) was used to calculate the
      parameters, using MATLAB software. The values of apparent K(m), K(i), and V(max)
      for imipramine glucuronidation via UGT1A4 were 1.39+/-0.09 mmol/L, 6.24+/-0.45
      mmol/L and 453.81+/-32.12 pmol/min per mg cell homogenate (n=3), respectively.
      CONCLUSION: As a specific substrate of UGT1A4, imipramine was used as a
      convenient method to characterize the activity of recombinant UGT1A4 by using
      HPLC. Furthermore, the profile of imipramine glucuronidation was evaluated by
      using recombinant UGT1A4 in vitro.

PMID- 16626520
TI  - Influence of age and sex on pharmacodynamics of propofol in neurosurgical
      patients: model development.
AB  - AIM: To determine propofol concentration in the cerebral spinal fluid (CSF) of
      neurosurgical patients and carry out a preliminary population pharmacodynamic
      study. METHODS: Twenty-seven elective neurosurgical patients (12 men and 15
      women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 min
      and an infusion of 10 mg/kg per h for 5 min. Frequent CSF samples were drawn and
      assayed for propofol concentration. The bispectral index (BIS) was used to
      measure the drug effect. All data were analyzed first with the Excel software
      package, then pharmacodynamics modeling was performed using the NONMEM software
      package. RESULTS: The CSF concentration was related to the drug effect with
      linear and sigmoid Emax models. The parameters for the linear addictive model
      were a=1.11 and b=95.4. The parameters for the linear exponential model were
      a=1.05 and b=92.7. The parameters for the sigmoid E(max) model were E(max)=119,
      EC(50)=53.6 ng/mL, and N=1.51. When the covariates of age, weight and sex were
      considered, the parameters of models, objective function, the standard error of
      the mean and the prediction error were not optimized. CONCLUSION: Linear
      additive, linear exponential and sigmoid E(max) models can be used to describe
      the pharmacodynamics of propofol with respect to the concentration in CSF. In
      this small population, age (17-74 years), weight (47-98 kg) and sex did not
      influence any of the pharmacodynamic parameters of propofol. To verify these
      preliminary results, a larger study population is required.

PMID- 16626521
TI  - Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal
      cytochrome P450 from in vivo and in vitro studies.
AB  - AIM: To study the in vivo and in vitro metabolism and the effect of para-toluene
      sulfonamide (PTS) on cytochrome P450 enzymes (CYP450). METHODS: Total CYP450 and
      microsome protein content were determined after iv pretreatment of rats with PTS.
      CYP-specific substrates were incubated with rat liver microsomes. Specific CYP
      isoform activities were determined by using HPLC. CYP chemical inhibitors added
      to the incubation mixture were used to investigate the principal CYP isoforms
      involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by
      incubating PTS with specific substrates. RESULTS: The groups treated with 33 and
      99 mg/kg per d PTS, respectively, had a total CYP content of 0.66+/-0.17 and
      0.60+/-0.12 nmol/mg. The K(m) and V(max) were 92.2 micromol/L and 0.0137 nmol/min
      per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in
      the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS
      metabolism were shown to have a mixed mechanism, whereas PTS metabolism was
      inhibited noncompetitively by quinidine. PTS had little effect on the activities
      of the selected CYP isoforms. CONCLUSION: Generally speaking, it is relatively
      safe for PTS to be co-administered with other drugs. However, care should be
      taken when administering PTS with CYP inhibitors and the substrates of CYP2C,
      CYP2D and CYP3A.

PMID- 16626522
TI  - Canadian Consensus Conference on menopause, 2006 update.
AB  - OBJECTIVE: To provide guidelines for health care providers on the management of
      menopause in asymptomatic healthy women as well as in women presenting with
      vasomotor symptoms, urogenital, sexual, and mood and memory concerns and on
      specific medical considerations, and cardiovascular and cancer issues. OUTCOMES:
      Prescription medications, complementary and alternative medicine (CAM), and
      lifestyle interventions are presented according to their efficacy in treating
      menopausal symptoms. EVIDENCE: MEDLINE and the Cochrane database were searched
      for articles from March 2001 to April 2005 in English on subjects related to
      menopause, menopausal symptoms, urogenital and sexual health, mood and memory,
      hormone therapy, CAM, and on specific medical considerations that affect the
      decision of which intervention to choose. VALUES: The quality of evidence is
      rated using the criteria described in the report of the Canadian Task Force on
      the Periodic Health Examination. Recommendations for practice are ranked
      according to the method described in this report (see Table 1). SPONSORS: The
      development of this consensus guideline was supported by unrestricted educational
      grants from Berlex Canada Inc, Lilly Canada, Merck Frosst, Novartis, Novogen,
      Novo Nordisk, Proctor and Gamble, Schering Canada, and Wyeth Canada.

PMID- 16626539
TI  - [Current status of percutaneous coronary intervention for chronic total
      occlusion].

PMID- 16626523
TI  - Canadian Consensus Conference on osteoporosis, 2006 update.
AB  - OBJECTIVE: To provide guidelines for the health care provider on the diagnosis
      and clinical management of postmenopausal osteoporosis. OUTCOMES: Strategies for
      identifying and evaluating high-risk individuals, the use of bone mineral density
      (BMD) and bone turnover markers in assessing diagnosis and response to
      management, and recommendations regarding nutrition, physical activity, and the
      selection of pharmacologic therapy to prevent and manage osteoporosis. EVIDENCE:
      MEDLINE and the Cochrane database were searched for articles in English on
      subjects related to osteoporosis diagnosis, prevention, and management from March
      2001 to April 2005. The authors critically reviewed the evidence and developed
      the recommendations according to the Journal of Obstetrics and Gynaecology
      Canada's methodology and consensus development process. VALUES: The quality of
      evidence is rated using the criteria described in the report of the Canadian Task
      Force on the Periodic Health Examination. Recommendations for practice are ranked
      according to the method described in this report. SPONSORS: The development of
      this consensus guideline was supported by unrestricted educational grants from
      Berlex Canada Inc., Lilly Canada, Merck Frosst, Novartis, Novogen, Novo Nordisk,
      Proctor and Gamble, Schering Canada, and Wyeth Canada.

PMID- 16626540
TI  - [Primary percutaneous coronary intervention in patients with acute myocardial
      infarction induced by left main artery occlusion or severe stenosis].
AB  - OBJECTIVE: The effects of primary percutaneous coronary intervention (PCI) in
      patients with acute myocardial infarction (AMI) induced by left main (LM) artery
      occlusion were analyzed retrospectively in this study. METHODS: A total of 1343
      consecutive AMI patients who underwent primary PCI between January 1995 and
      December 2004 were retrospectively studied. RESULTS: LM occlusion or severe
      stenosis were found in 11 patients [all male, mean age (56.4 +/- 9.2) years
      (range 43-70 years)], cardiogenic shock was overt in 6 patients. Primary PCI were
      performed under the assistance of intra-aortic balloon pump (IABP) in these
      patients [8 stent implantation, 3 balloon dilation and 2 necessitating emergency
      CABG after balloon dilation]. In-hospital mortality was 45.5% (5/11). Three-month
      follow-up were made in all survivals (6/11). Analysis showed good collateral
      circulation flow from right coronary artery to left coronary artery was existed
      in all survival cases before PCI. CONCLUSION: Prognosis of AMI patients with LM
      artery obstruction or severe stenosis was poor. Patients with pre-existed
      collateral circulation before primary PCI and IABP had a better clinical
      outcomes.

PMID- 16626541
TI  - [Clinical outcomes of treating bifurcation lesions with two drug-eluting stent
      techniques].
AB  - OBJECTIVE: To evaluate the clinical outcomes of treating bifurcation lesions with
      two drug-eluting stent (DES) techniques. METHODS: From October 2003 to February
      2005, Seventy-one patients with 72 bifurcation lesions (the ostium of side branch
      > 2.5 mm in diameter) were treated by two DES. Forty-five of the bifurcation
      lesions were located in LAD/Diagonal (62.5%), 20 in distal left main coronary
      arteries (27.8%), 6 in LCX/OM (8.3%) and 1 distal RCA (1.4%). The Crush or
      modified Crush technique was used in 42, "T" technique in 19, modified "Y"
      technique in 5, "V" technique in 3 and Culotta technique in 3 bifurcation
      lesions, respectively. Fifty-nine Cypher or Cypher Select stents, 48 TAXUS
      stents, 25 Firebird stents and 24 bare metal stents were used for 144 lesions.
      Final kissing balloon inflation was performed in 60 bifurcation lesions (83.3%)
      after stenting procedure. RESULTS: Success rate of PCI procedure for the
      bifurcation lesions was 100%. One patient developed subacute stent thrombosis and
      underwent successful urgent revascularization. In-hospital major adverse cardiac
      events (MACE, death, AMI, revascularization) rate was 1.4% (1/71). Six months
      follow-up was made in 16 patients. No death and AMI occurred during the follow-up
      period in these patients. Total occlusion in ostium of the diagonal vessel was
      found in one patient with LAD/Diagonal bifurcation lesion 6 months post
      procedure. MACE rate during the follow-up was 6.3% (1/16). CONCLUSION: This study
      showed that the use of two DES techniques for the treatment of bifurcation
      lesions was safe and effective. The short-term outcome for this strategy was very
      satisfactory and primary data of 6-month follow-up also showed satisfactory
      results.

PMID- 16626542
TI  - [Arsenic trioxide eluting stents to prevent restenosis of injured iliac arteries
      in rabbits].
AB  - OBJECTIVE: To assess the efficiency of eluting stent coated with arsenic trioxide
      (As(2)O(3)) suspended in poly-L-lactic acid (PLLA) to prevent in-stent restenosis
      in rabbits. METHODS: Forty-five male New Zealand white rabbits were assigned to
      three groups (n = 15 for each group) at random: uncoated stents, stents coated
      with PLLA or stents coated with As(2)O(3) in PLLA. Animals were euthanized 28
      days after stent implantation into the iliac arteries of rabbits. Neointimal
      thicknesses and apoptosis of vascular smooth muscle cell (VSMC) were measured.
      Stents coated with As(2)O(3) in PLLA were implanted in another 48 male New
      Zealand white rabbits, As(2)O(3) concentrations in serum and arterial tissue at
      implantation site were measured at 2 h and 1, 3, 7, 14, 28 days after As(2)O(3)
      eluting stent implantation (n = 8 for each time point). RESULTS: Neointimal
      hyperplasia was significantly reduced 51% and 31% and apoptosis significantly
      increased (21.0 +/- 3.3; 6.2 +/- 1.9(*); 5.3 +/- 2.1(*), (*)P < 0.01 vs.
      As(2)O(3) eluting stent) with As(2)O(3) eluting stent, versus PLLA-coated stents
      and uncoated stents. As(2)O(3) concentrations in arterial tissue at implantation
      site were 18.6 +/- 9.1 (ng/mg) at 1 day and 0.3 +/- 0.1 (ng/mg) at 28 days after
      stent implantation. CONCLUSIONS: As(2)O(3) coated stents released As(2)O(3) to
      local tissue for at least 28 days, suppressed neointimal hyperplasia in rabbit
      iliac arteries and increased local VSMC apoptosis might be one of the mechanisms
      for inhibiting restenosis by As(2)O(3) coated stents.

PMID- 16626543
TI  - [Determining the relationship between coronary artery and coronary sinus and its
      tributaries using multislice computed tomography].
AB  - OBJECTIVE: To obtain the coronary artery and coronary sinus (CS) and its
      tributaries imaging with multislice computed tomography (MSCT), measure the
      distance between coronary artery and CS and its tributaries and analyze their
      spatial relationships. METHODS: The MSCT scans of 117 patients (67 men, 50 women,
      age 56 +/- 10 years) were obtained, 3D image reconstructed and the vessels
      courses evaluated. The concomitant distances and spatial relationships of the
      vessels were determined. RESULTS: Right coronary artery domination was found in
      107 cases (91.4%), left coronary artery domination in 7 cases (6.0%), and co
      domination in 3 cases (2.6%). Left circumflex artery (LCX) was concomitant with
      CS or the great cardiac vein (GCV) in 81 cases (69.2%), intersected with left
      posterior vein in 62 cases (53.0%) and with middle cardiac vein (MCV) in 5 cases
      (4.3%), respectively. The dominant coronary artery branched out into the
      posterior descending artery (PDA) and the left posterior artery (LPA) in 112
      cases (95.7%). PDA was concomitant with MCV in 93 cases (79.5%) and intersected
      with MCV in 44 cases (37.6%). LPA was intersected with MCV in 106 cases (90.6%),
      and concomitant with CS in 50 cases (42.7%). CONCLUSIONS: MSCT is a reliable tool
      to visualize the relationship between coronary artery and CS and its tributaries.
      Owing to the multiple possibilities inherent to this technique, MSCT has broad
      potential for more clinical use.

PMID- 16626544
TI  - [Acute hemodynamic effects of intravenous recombinant human brain natriuretic
      peptide in patients with acute myocardial infarction complicated with heart
      failure].
AB  - OBJECTIVE: To compare the acute hemodynamic effects and safety of intravenous
      injection of recombinant human brain natriuretic peptide (rhBNP) versus
      intravenous nitroglycerin (NIT) in acute myocardial infarction (AMI) patients
      with heart failure. METHODS: On top of standard therapy, 42 consecutive patients
      who suffered from anterior wall AMI with heart failure [pulmonary capillary wedge
      pressure (PCWP) > 16 mm Hg] within 12 to 24 hours from the onset of chest pain
      were randomized into rhBNP group (n = 21, 1.5 microg/kg bolus intravenous
      injection followed by 0.0075 microg.kg(-1).mn(-1) for the first 3 hours and 0.015
      0.03 microg.kg(-1).mn(-1) infusion for following 21 hours) and NIT group (n = 21,
      10 to 100 microg/mn intravenous infusion for 24 hours). The hemodynamic
      parameters were monitored by Swan-Ganz catheter at baseline, during drug infusion
      and 6 hours post infusion withdraw; total urine output was also obtained. The
      major adverse cardiac events (MACE) were observed up to 1 week after drug
      infusions. RESULTS: Central venous pressure and systolic blood pressure remained
      unchanged after rhBNP or NIT infusion. Compared to baseline level, PCWP was
      significantly reduced by 48.9% (P < 0.01) at 30 minutes after rhBNP infusion and
      this effect remained up to 6 hours post infusion withdraw; PCWP reduced by 28.7%
      (P < 0.05) at 2 hours after NIT infusion and this effect remained to 6 hours
      before infusion withdraw. Cardiac index (CI) was increased by 27.1% (P < 0.05) at
      1 hour after rhBNP infusion and remained till 6 hours post infusion withdraw; CI
      was significantly increased at 3 hour after NIT infusion and this effect
      disappeared after infusion withdraw. The PCWP and CI values were significantly
      higher in rhBNP group than that of NIT group at 30 minutes and 2 hours (P <
      0.05). Heart rate was significantly reduced at 30 minutes (95.3 +/- 7.4 vs. 118.0
      +/- 8.2 bpm, P < 0.05) and at 2 hour (92.8 +/- 6.8 vs. 109.2 +/- 7.6 bpm, P <
      0.05) in rhBNP and NIT group, respectively and heart rate remained reduced during
      the whole infusion period in both groups. The total urine output for 30 hours in
      rhBNP group (1870 +/- 535 ml) tended to be higher than that in NIT group (1538 +/
      620 ml, P > 0.05). There was no symptomatic hypotension or other adverse events
      during drug infusion in both groups and MACE up to 1 week post drug infusion was
      also similar between the two groups. CONCLUSION: Intravenous injection of rhBNP
      results in more rapid and long-lasting hemodynamic improvements than that of NIT
      in AMI patients with heart failure and it is also feasible and safe for clinic
      use in AMI patients with heart failure.

PMID- 16626545
TI  - [Prognostic value of N-terminal-pro-brain natriuretic peptide on admission in
      patients with chronic heart failure].
AB  - OBJECTIVE: Heart failure is responsible for a huge burden in hospital care. Our
      goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide (Nt
      proBNP) on predicting death or hospital readmission after hospital discharge in
      patients with chronic heart failure (CHF). METHODS: From March 2003 to April
      2005, 135 consecutive patients (97 male and 38 female, mean age 60.7 years +/-
      13.1 years) with chronic heart failure [dilated cardiomyopathy (44%) and coronary
      heart disease (35%)] were included in this study. Plasma concentrations of the Nt
      proBNP were measured by ELISA on admission. All patients received conventional
      therapy and were followed up for 24 months. The primary end point was death or
      readmission. RESULTS: (1) During the follow up period (640 days +/- 100 days), 11
      patients died and 39 patients rehospitalized, the median Nt-proBNP level on
      admission was significantly higher in patients died during the follow up period
      (5908 ng/L) than that of rehospitalized patients (2768 ng/L, P = 0.038). Plasma
      Nt-proBNP level on admission were significantly higher in primary end point group
      (n = 50, 2947 ng/L) than that in non-primary end point group (n = 85, 917 ng/L, P
      < 0.01). (2) Variables associated with an increased hazard of death and/or
      rehospitalization were Nt-proBNP and NYHA degree when analyzed by logistic
      regression models. Increased Log Nt-proBNP was the strongest independent
      predictor of an adverse outcome of CHF (odds ratio 13.8, 95% confidence interval
      2.29 to 2.78, P < 0.01). (3) Area under the curve for Nt-proBNP in evaluating
      prognosis of CHF patients was 0.885 (positive predictive value 88.5%, negative
      predictive value 11.5%). CONCLUSION: Nt-proBNP level on admission is a strong
      predictor of rehospitalization and death within 24 months after hospital
      discharge in patients with chronic heart failure.

PMID- 16626546
TI  - [Human inward rectifying potassium current and Kir2.1 mRNA expression in myocytes
      isolated from patients with chronic atrial fibrillation].
AB  - OBJECTIVE: To compare the changes of both inward rectifying K(+) (Kir)
      current(I(k1)) density and mRNA expression level of Kir2.1, a major subfamily of
      Kir in chronic human atrial fibrillation (CAF) with those in normal sinus rhythm
      (NSR). METHODS: I(k1) density was measured with whole-cell patch clamp technique
      in single myocyte isolated by an enzymatic dissociation method from right atrial
      appendages in patients with CAF (n = 8) and those with NSR (n = 12). The mRNA
      expression levels of Kir2.1 was determined in right atrial appendages from CAF (n
      = 19) and NSR (n = 18) by semiquantitative reverse-transcription polymerase chain
      reaction (RT-PCR). RESULT: The average resting membrane potentials were similar
      between CAF and NSR (-78.95 mV +/- 4.67 mV and -70.22 mV +/- 11.08 mV, P>0.05).
      I(k1) density in single myocyte significantly increased at hyperpolarized
      potential level (-100 mV) in CAF compared to that in NSR (-9.59 pA/pF +/- 2.47
      pA/pF vs. -5.58 pA/pF +/- 2.52 pA/pF, P<0.01). The mRNA level of Kir2.1 was also
      significantly higher in CAF than that of NSR (0.50+/-0.16 vs. 0.34+/-0.09,
      P<0.05). CONCLUSION: The data suggest that Kir2.1 up-regulation and I(k1) current
      increase might contribute to the electrical remodeling in CAF patients.

PMID- 16626547
TI  - [Endothelial function evaluation in salt-sensitive normotensive and mild
      hypertensive subjects and effects of potassium supplement].
AB  - OBJECTIVE: Salt-sensitivity plays an important role in essential hypertension and
      is associated with more severe target organ injury and higher mortality in
      patients with essential hypertension. However, the pathologic mechanism of salt
      sensitivity is poorly understood and endothelial dysfunction might be involved in
      salt-sensitive hypertension. We, therefore, observed the endothelial function
      changes by measuring plasma and urine nitric oxide (NO) concentrations in salt
      sensitive (SS) normotensive and mild hypertensive subjects underwent various salt
      loading protocols and the effects of potassium supplement. METHODS: Thirty-nine
      normotensive and mild hypertensive subjects (< 160/100 mm Hg), aged 16-60, were
      enrolled and the study protocol is as follows: 3 days baseline investigation, 1
      week low-salt loading (3 g/day), 1 week. high-salt loading (18 g/day) and 1 week
      high-salt loading plus potassium chloride (4.5 g/day). RESULTS: Plasma and urine
      NO levels were significantly lower in SS (n = 8) subjects at baseline, low-salt
      and high-salt loading phases compared with salt-resistant subjects (SR, n = 31)
      and oral potassium supplement to SS subjects with high salt loading significantly
      increased plasma and urine NO levels. CONCLUSION: Endothelial function is
      impaired in normotensive and mild hypertensive SS subjects. Oral potassium
      supplement could improve endothelial function in normotensive and mild
      hypertensive SS subjects.

PMID- 16626549
TI  - [Involvement of p53-dependent pathway in the antiproliferative activity of emodin
      in human smooth muscle cell].
AB  - OBJECTIVE: To investigate whether p53 pathway participates in the effect of
      emodin on vascular smooth muscle cell proliferation. METHODS: The effects of
      emodin on vascular smooth muscle cell proliferation were evaluated by cell count,
      senescent-associated beta-galactosidase staining, and annexin V staining. DNA
      synthesis was determined by (3)H-thymidine corporation, cell cycle was analyzed
      by FACS, the p53 protein level was measured by Western blot and cDNA expression
      array technology was used to demonstrate the effect of emodin on the simultaneous
      expression of a large number of genes in cultured vascular smooth muscle cells.
      RESULTS: Emodin at 1.6-3.1 microg/ml inhibited VSMC growth, at 6.3-12.5 microg/ml
      promoted VSMC aging and induced VSMC apoptosis at 25.0 microg/ml 24 hours after
      exposure. Unscheduled DNA synthesis, which was a sensitive indicator for DNA
      injury, was observed in VSMC following 24 hours emodin exposure. The mRNA and
      protein levels of p53 were up-regulated in a concentration-dependent manner.
      Proliferation/carcinogenesis-related genes were down-regulated and other genes
      related to cell senescence, apoptosis, and DNA damage/repair were up-regulated in
      VSMC after exposure to emodin for 24 hours. Emodin readily permeated VSMC
      membrane and mostly located in the cytoplasm and few of them in the nucleus.
      CONCLUSIONS: The p53 pathway in VSMC was activated post emodin exposure in a
      concentration-dependent manner and which might be responsible for the observed
      antiproliferative effects of emodin in vascular smooth muscle cells.

PMID- 16626550
TI  - [Upregulated Rho-kinase and increased phosphorylation of myosin-binding subunit
      of myosin phosphates are key players in a porcine coronary artery spasm model
      with interleukin-1beta].
AB  - OBJECTIVE: Phosphorylation of myosin light chain (MLC) is one of the most
      important steps for vascular smooth muscle contraction and Rho-kinase is involved
      in this process. We investigated the role of Rho-kinase in a porcine coronary
      artery spasm model with interleukin-1beta. METHODS: Segments of left coronary
      artery adventitia were surrounded by normal saline (n = 8) or IL-1beta agarose
      microne (n = 8) for 2 weeks. Vasospastic responses to intracoronary serotonin or
      histamine then studied at the saline or IL-1beta-treated site. The Rho-kinase
      mRNA expression in the treated site was measured by reverse transcription
      polymerase chain reaction analysis (RT-PCR). The extent of phosphorylation of
      myosin-binding subunit of myosin phosphates (MBS, one of the major substrates of
      Rho-kinase) were quantified by Western blot analysis. RESULTS: Intracoronary
      serotonin or histamine repeatedly induced coronary artery spasm and coronary
      arterial stenosis was evidenced at IL-1beta-treated site. Expression of Rho
      kinase mRNA in IL-1beta-treated site was significantly increased compared to
      saline treated site (98.20% +/- 7.66% vs. 63.70% +/- 4.26%, P < 0.05). Western
      blot analysis showed that during the serotonin-induced contractions the extent of
      phosphorylation of MBS was also significantly increased in the spastic site
      (25,485 +/- 4745 vs. 6510 +/- 779, P < 0.05). CONCLUSION: Rho-kinase upregulation
      at the spastic site and increased phosphorylation of myosin-binding subunit of
      myosin phosphates are key players in inducing vascular smooth muscle
      hypercontraction in this porcine model.

PMID- 16626551
TI  - [Selective knockdown of Angiotensin II receptor subtype 1a in rat vascular smooth
      muscle cells by RNA interference].
AB  - OBJECTIVE: To selectively knockdown the expression of Angiotensin II receptor
      subtype 1a (AT1aR) in rat vascular smooth muscle cells (VSMCs) by RNA
      interference and the sequential effects on cellular viability and proliferation.
      METHODS: The primary cultured rat aortic VSMCs were transfected by plasmids pAT1a
      shRNA1 and pAT1a-shRNA2, each carrying an U6 promoter and an AT1a-specific shRNA
      coding template sequence, or by a control plasmid pGenesil-Control (pCon)
      carrying a nonspecific shRNA-coding sequence. The mRNA and protein expressions of
      AT1a, AT2 were analyzed by semi-quantified RT-PCR and Western blot, respectively
      and normalized to the internal control gene beta-actin. Cellular viability and
      proliferation were determined with methylthiazoletetrazolium (MTT) assay.
      RESULTS: AT1a mRNA and protein were reduced by 82% and 69% by pAT1a-shRNA1, 77%
      and 56% by pAT1a-shRNA2, respectively while no change was found in pCon treated
      VSMCs. AT2 receptor level in VSMCs remains unchanged after various treatments.
      The A(490nm) values obtained by MTT measurements were similar among groups in the
      absence of Ang II but decreased significantly in pAT1a-shRNA1 and pAT1a-shRNA2
      treated VSMCs in the presence of Ang II. CONCLUSION: RNA interference can
      selectively knockdown AT1a expression in cultured VSMCs and attenuate the Ang II
      induced cell proliferation. Future studies are warranted to explore the potential
      role of RNA interference on AT1 function and as a new gene therapy tool for
      cardiovascular diseases.

PMID- 16626553
TI  - [Ultrastructural study of the pulmonary veins in pigs].
AB  - OBJECTIVE: To explore the possible relationship between the ultrastructural
      characteristics of pulmonary veins and the pathogenesis of atrial fibrillation
      originating from pulmonary veins. METHODS: The pulmonary veins from domestic pigs
      were serially sectioned (2 mm) transversely along the vessels. The odd number
      sections were fixed in 10% phosphate buffered formalin solution and the even
      number sections were fixed in 3% Glutaral for further electron microscopy
      observations. RESULTS: Two cell types were found in the pulmonary veins of pigs.
      One cell type was the P-like cells that had an empty-appearing cytoplasm
      containing only sparse myofibrils and small mitochondria, both of which were
      randomly distributed. Another cell type was slender transitional cells with
      plenty of longitudinally displayed myofibrils. CONCLUSION: P-like cells in the
      pig pulmonary veins were found using electron microscopy in this study and
      ectopic beats from P-like cells in the myocardial sleeves in the pulmonary veins
      might be responsible for atrial fibrillation originating from pulmonary veins.

PMID- 16626552
TI  - [Effects and mechanism of hyperglycemia on development and maturation and immune
      function of human monocyte derived dendritic cells].
AB  - OBJECTIVE: Dendritic cells play an important role in the pathogenesis of
      atherosclerosis. To explore the effects of hyperglycemia on the maturation and
      immune function of human monocyte derived dendritic cells (MDCs). METHODS:
      Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose
      (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol
      (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive
      oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the
      MDCs immunophenotypic expression. Immune function was evaluated by allogeneic
      mixed T lymphocyte reaction and measurement of cytokine levels from culture
      supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'
      dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser
      scanning microscopy techniques. RESULTS: Compared with NG and HM treated MDCs,
      the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were
      significantly upregulated, allogeneic T cells proliferation as well as the
      cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased
      in HG treated MDCs. Intracellular ROS production in MDCs was also significantly
      increased and all these stimulatory effects of HG could be partially attenuated
      by NAC. CONCLUSION: High glucose promote the maturation of MDCs and augment their
      capacity to stimulate T-cell proliferation and cytokine secretions at least in
      part through enhancing intracellular ROS generation. These stimulating effects of
      high glucose on MDCs maturation may be one of the mechanisms of accelerated
      atherosclerosis found in patients with diabetes.

PMID- 16626567
TI  - [Cyclooxygenase-2 and atherosclerosis: disputation and prospect].

PMID- 16626568
TI  - [Pharmacogenomics of statin therapy].

PMID- 16626570
TI  - [Current status of stem cell transplantation for treatment of cardiovascular
      diseases in China].

PMID- 16626571
TI  - [Safety and efficacy of intracoronary transplantation of G-CSF mobilized
      autologous peripheral blood stem cells in patients with acute myocardial
      infarction].
AB  - OBJECTIVE: To investigate the safety and efficacy of intracoronary
      transplantation of G-CSF mobilized autologous peripheral blood stem cells in
      patients with acute myocardial infarction (AMI). METHODS: Patients with AMI were
      randomly assigned to receive intracoronary PBSCs transplantation following bone
      marrow cells mobilization by granulocyte colony-stimulating factor (300-600
      microg/day subcutaneously for 5 days) in addition to standard therapy (standard
      drug therapy and PCI, PBSCs transplantation group, n = 35) or standard therapy
      (standard drug therapy and PCI, n = 35). One day after G-CSF treatment was
      finished the patient's mononuclear cells were harvested by Baxter CS 3000 blood
      cell separator in a volume of 57 ml and then transferred into the infarct related
      artery by occluding the over the wire balloon and infusing artery through balloon
      center lumen. Complications during intervention and left ventricular function at
      baseline and 6 months thereafter were monitored. RESULTS: No severe side effects
      of G-CSF treatment could be observed. Malignant arrhythmias were not observed
      either. Left ventricular function was significantly improved 6 months after G-CSF
      mobilized autologous peripheral blood stem cell transplantation compared to
      baseline (global left ventricular function ejection fraction: 57.1 +/- 7.8 vs.
      50.0 +/- 8.2%, P < 0.0001; WMSI: 1.101 +/- 0.118 vs. 1.219 +/- 0.190, P < 0.0001;
      left end-systolic volume: 52.6 +/- 20.3 vs. 63.8 +/- 23.9 ml, P = 0.01 and left
      end-diastolic volume: 119.2 +/- 30.3 vs. 134.2 +/- 36.7 ml, P = 0.07) while these
      parameters remained unchanged in the control group. CONCLUSION: The present study
      demonstrates that G-CSF mobilized autologous intracoronary PBSCs transplantation
      is a safe and feasible treatment for patients with AMI and global left
      ventricular function is improved and left ventricular remodeling attenuated at
      six-month follow-up.

PMID- 16626572
TI  - [Effects of intracoronary autologous bone marrow mononuclear cells
      transplantation in patients with anterior myocardial infarction].
AB  - OBJECTIVES: To investigate the efficacy of intracoronary transfer of autologous
      bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction
      (MI) on left ventricular function and myocardial perfusion. METHODS: Thirty-five
      patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled
      study (20 patients in cell transplantation group; 15 patients in control group).
      All patients were treated by standard drug therapy and percutaneous coronary
      intervention (PCI). Baseline and 3 months follow-up evaluations included complete
      clinical and laboratory examinations, six minutes walk test, echocardiography,
      Dual-isotope simultaneous acquisition single photon emission computed tomography
      (DISA-SPECT) and cardiac magnetic resonance imaging (MRI). RESULTS: Baseline
      parameters were similar between the two groups. NYHA classification and six
      minutes walk test at 3 months follow-up were also similar between the two groups.
      However, left ventricular ejection fraction (LVEF) determined by echocardiography
      and DISA-SPECT was significantly higher; regional wall motion measured by
      echocardiography and cardiac MRI, myocardial viability and myocardial perfusion
      in the infarct zone assessed by DISA-SPECT were all significantly improved than
      before transplantation and than that in control group at 3 months follow-up.
      CONCLUSIONS: Our results indicate that intracoronary transplantation of ABMMNCs
      could improve the left ventricular systolic function and beneficially affect
      myocardial perfusion up to 3 months post transplantation in patients with
      myocardial infarction.

PMID- 16626573
TI  - [A prospective, randomized, controlled trial of autologous mesenchymal stem cells
      transplantation for dilated cardiomyopathy].
AB  - OBJECTIVE: Recent experimental and clinical observations have suggested that cell
      transplantation could be of therapeutic value for the treatment of heart failure.
      This study was performed to explore the efficacy and safety of intracoronary
      autologous mesenchymal stem cells (MSCs) transplantation for treating patients
      with idiopathic dilated cardiomyopathy. METHOD: Twenty-four consecutive patients
      with idiopathic dilated cardiomyopathy received standard drug therapy were
      randomly divided into intracoronary injection of autologous mesenchymal stem
      cells (treated, n = 12) or saline (control, n = 12) groups. Serum IL-6, TNF-alpha
      and CRP, plasma brain natriuretic peptides (BNP) were determined and
      echocardiography, Holter electrocardiogram monitoring and six minutes walk test
      were performed at baseline, 3 and 6 months post injection. RESULTS: IL-6, TNF
      alpha and CRP remained unchanged after MSCs transplantation. Plasma BNP levels at
      3 months and 6 months post MSCs injection were significantly higher than that of
      pre-injection (378.10 +/- 147.47, 420.40 +/- 148.50 vs. 292.40 +/- 148.54 ng/L,
      respectively, P < 0.05) but were significantly lower than that in control group
      at comparable time points (3 months: 378.10 +/- 147.47 vs. 473.10 +/- 106.31
      ng/L; 6 months: 420.40 +/- 148.50 vs. 544.60 +/- 93.11 ng/L, P < 0.05). Six
      minute-walking distance significantly increased at 6 months after MSCs injection
      compared with pre-injection level and which is also higher than that in control
      patients (519.00 +/- 43.28 vs. 396.33 +/- 42.19 and 464.00 +/- 76.5 m,
      respectively, P < 0.05). Left ventricular ejection fraction and LVEDd remained
      unchanged post MSCs injection. No malignant arrhythmias and severe side effects
      could be observed around transplantation and during six months follow-up.
      Survival was similar between the two groups during six months follow-up.
      CONCLUSION: Percutaneous coronary autologous mesenchymal stem cells
      transplantation can attenuate the increase of plasma BNP, increase six-minute
      walking capacity in patients with idiopathic dilated cardiomyopathy.

PMID- 16626574
TI  - [Transplantation of autologous bone marrow mononuclear cells on patients with
      idiopathic dilated cardiomyopathy: early results on effect and security].
AB  - OBJECTIVE: The aim of this study is to identify short-term result of cell
      transplantation in idiopathic dilated cardiomyopathy (IDC) patients who were
      treated by intracoronary transplantation of autologous mononuclear bone marrow
      cells (BMCs) in addition to standard therapy. METHODS: Based on given standard
      therapy, eighteen patients with idiopathic dilated cardiomyopathy were enrolled
      and divided into transplantation group and control group. The clinical
      characteristics of two groups were comparable. Among these patients, 10 patients
      were performed percutaneous coronary autologous BMCs transplantation. Blood
      routine test, hepatic function, renal function, glucose, triglyceride (TG),
      cholesterol, low density cholesterol (LDL), high density cholesterol (HDL), uric
      acid (UA) and high sensitive C-reactive protein (hsCRP) were measured at the time
      point of pre-operation and some time after transplantation. All patients were
      monitored under ultrasonic cardiography, Holter, six-minute-walk test and
      magnetic resonance imaging over a period of at least 6 months. Annual hospital
      days were recorded during two-year follow-up. RESULTS: Blood routine test,
      hepatic function, renal function, glucose, TG, cholesterol, LDL, HDL, UA and
      hsCRP had no significant differences among 48 hours, 3 months and 6 months after
      transplantation compared with control and pre-transplantation (P > 0.05). Six
      minute-walk distance elevated significantly six months after BMCs transplantation
      compared with control and pre-transplantation [(494.3 +/- 62.8) m vs (307.2 +/-
      75.0) m, (321.5 +/- 63.7) m, P < 0.05]. Left ventricular ejection fraction (LVEF)
      and the sizes of LVEDd had no significant changes compared with that of control
      and pre-transplantation (P > 0.05). Myocardium lesion area measured by (MRI)
      seemed decrease in transplantation group compared with that of control and pre
      operation [(4.96 +/- 0.47) cm(2) vs (5.12 +/- 0.54) cm(2), (5.02 +/- 0.39) cm(2),
      P > 0.05], but there was no significance. None of proarrhythmias and side effects
      had been observed around transplantation and 2 years follow-up. There was no
      significant difference in survival between two groups in 2 years follow-up.
      Interestingly, annual hospital day in BMCs transplantation patients was
      significantly shorter than that in control group [(30.2 +/- 11.2) d vs (43.6 +/-
      9.8) d, P < 0.05]. CONCLUSIONS: Autologous bone marrow mononuclear cells
      transplantation can prolong six-minute-walk, decrease re-hospitalization rate,
      elevate exercise ability and help to improve cardiac function in patients with
      IDC. In addition, it was demonstrated that cell transplantation is safe.

PMID- 16626575
TI  - [Time course of G-CSF, estrogen and various doses of atorvastatin on endothelial
      progenitor cells mobilization].
AB  - OBJECTIVE: To evaluate the time course of granulocyte-colony-stimulating-factor
      (G-CSF), estrogen and various doses of atorvastatin on endothelial progenitor
      cells (EPCs) mobilization. METHOD: A total of 48 male New Zealand White rabbits
      were treated with placebo, estrogen (0.25 mg.k(-1).d(-1)), Atorvastatin (2.5, 5,
      or 10 mg) and G-CSF (50 microg/rabbit/d), respectively. Peripheral EPCs number
      was surveyed weekly for 4 weeks by FACS analysis (double-positive for PE
      CD34/FITC-CD133) and under fluorescent microscope (double-positive for FITC-UEA
      1/Dil-acLDL). Serum nitric oxide (NO) and lipids were also measured at the third
      week. RESULTS: Peripheral EPCs was significantly increased in G-CSF treated
      animals and remained constant for 4 weeks compared to placebo treated animals.
      Atorvastatin increased peripheral EPCs dose-dependently from 2.5 to 5 mg and
      peaked at the third week while peripheral EPCs number was not affected by 10
      mg.k(-1).d(-1) atorvastatin during the first 3 weeks and was significantly higher
      only in the fourth week compared to placebo group. Estrogen also significantly
      increased peripheral EPCs at the third and fourth week compared to placebo group.
      At the third week, serum NO was similar in G-CSF group, significantly higher in
      atorvastatin 5 mg.k(-1).d(-1) and estrogen groups while significantly lower in
      atorvastatin 10 mg.k(-1).d(-1) group compared to placebo group. Serum lipids were
      similar among various groups. CONCLUSION: Atorvastatin, estrogen and G-CSF could
      mobilize EPCs. The mobilization efficacy is as follows: G-CSF > atorvastatin 5
      mg.k(-1).d(-1) > estrogen > atorvastatin 2.5 mg.k(-1).d(-1) > atorvastatin 10
      mg.k(-1).d(-1). NO might partly contribute to the mobilizing effect of estrogen
      and atorvastatin.

PMID- 16626576
TI  - [Hepatocyte growth factor did not enhance the effects of bone marrow-derived
      mesenchymal stem cells transplantation on cardiac repair in a porcine acute
      myocardial infarction model].
AB  - OBJECTIVE: To evaluate the impact of combined therapy with transplanting bone
      marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery
      and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model.
      METHODS: BM-MSCs were obtained from pig bone marrow, expanded in vitro with a
      purity of > 50%. MI was induced by ligating the distal left anterior descending
      artery in pigs. Eighteen animals received BM-MSCs cells (5 x 10(6)/ml, n = 6), BM
      MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) pfu, n = 6) or equal volume culture
      medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated
      myocardial perfusion imaging and coronary angiography were performed before and
      four weeks after transplantations. Histological examination was also performed 4
      weeks after transplantation. RESULTS: LVEF measured by gated myocardial perfusion
      imaging was similar among groups before transplantation and significantly
      increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/-
      6 vs. 34 +/- 3%, P < 0.05) treated animals while remained unchanged in IMDM (30
      +/- 3 vs. 32 +/- 2%) treated animals 4 weeks post transplantation. Similarly,
      capillary density was also significantly higher and myocardial perfusion defect
      scores significantly decreased in BM-MSCs or BM-MSCs + HGF treated hearts than
      that in IMDM treated hearts. However, all these changes were similar between BM
      MSCs and BM-MSCs + HGF groups. Rentrop score was similar before and 4 weeks after
      transplantation among various groups. CONCLUSION: HGF in combination with BM-MSCs
      transplantation did not enhance the cardiac repair effects of BM-MSCs
      transplantation alone and BM-MSCs transplantation did not improve collateral
      circulation in this model.

PMID- 16626577
TI  - [Comparison of Rapamycin and Paclitaxel eluting stent in patients with multi
      vessel coronary disease].
AB  - OBJECTIVE: To Compare the efficacy and safety of Rapamycin (Cypher) and
      Paclitaxel (TAXUS) eluting stents for multi-vessel coronary diseases. METHODS:
      From June 2003 to December 2004, a total of 416 patients with multi-vessel
      coronary diseases were randomly treated with Rapamycin (n = 210) and Paclitaxel
      (n = 206) eluting stents. Patients with left main lesion, acute myocardial
      infarction, revascularization were not included. Acute and long-term outcomes
      were compared between the two groups. RESULTS: Baseline clinical characteristics,
      including risk factors of coronary heart disease, coronary lesion type, heart
      function, rates of success and complication of percutaneous coronary intervention
      procedure in the two groups were comparable. Number of stents implanted was not
      significantly different between the two groups (3.24 +/- 1.25 vs 3.19 +/- 1.38, P
      > 0.05). Mean follow-up duration was (19.5 +/- 8.9) months. Follow-up rate (96.2
      vs 95.1%), angina pectoris reoccurrence (4.0 vs 6.1%), restenosis (7.1 vs 9.6%),
      major adverse cardiac event (6.4 vs 8.8%) and event free survival (93.1 vs 91.3%)
      during follow-up were not significantly different between the two groups.
      Subacute stent thrombosis rate tended to be higher in Paclitaxel eluting stent
      group compared with Rapamycin eluting stent group (1.0% vs 0.5%, P > 0.05). At 6
      to 9 months angiographic follow-up, the in-stent minimal lumen diameter (MLD) and
      the in-segment MLD were similar between the two groups. CONCLUSIONS: Satisfactory
      acute and long term outcomes for patients with multi-vessel coronary disease were
      achieved by both Cypher and TAXUS stent implantation and the safety and efficacy
      of the two kinds of stents were comparable.

PMID- 16626578
TI  - [A randomized comparative study of using enoxaparin or UFH adjunctive to
      percutaneous coronary intervention in patients with CHD (ROUTE)].
AB  - OBJECTIVE: To evaluate the efficacy and safety of using Enoxaparin instead of UFH
      for patients with coronary heart disease (CHD) underwent coronary angiogram with
      or without percutaneous coronary intervention (PCI). METHODS: From Oct. 2003 to
      Feb. 2005, 966 patients with CHD underwent coronary angiogram (CAG) were
      randomized to receive enoxaparin (1 mg/kg subcutaneously, Q12 h, at least twice
      before CAG and the sheath was withdrawn immediately after the procedure, n = 484)
      or UFH (25 mg, iv, before CAG with additional 65 mg iv if PCI indicated and the
      sheath was withdrawn 4 hours after the procedure, n = 482). RESULTS: (1) PCI was
      not performed in 511 patients due to mild lesions or patients were suitable for
      CABG. In 455 patients underwent PCI (227 in enoxaparin and 228 in UFH group), 1
      patient in enoxaparin group developed acute thrombosis and resulted in AMI during
      PCI and underwent successful urgent revascularization. The incidence of in
      hospital major adverse cardiac events were 0.44% in the enoxaparin group and 0 in
      the UFH group. (2) Hematoma at the puncture site happened in 8 patients (3.5%) in
      enoxaparin group and in 20 patients (8.8%, P < 0.05) in UFH group. (3) One
      patient had AMI caused by subacute thrombosis in UFH group during 1 month follow
      up. CONCLUSIONS: Our results suggest that the effects and safety are comparable
      for enoxaparin and UFH, it is also safe and efficient to give enoxaparin at least
      twice before CAG/PCI and the sheath can be withdrawn immediately after PCI. For
      ACS patients received more than twice enoxaparin and the last dose was given
      within 8 hours before PCI, PCI could be performed directly without additional
      UFH.

PMID- 16626579
TI  - [Coronary artery atherosclerotic plaque and stent visualizations by optical
      coherence tomography].
AB  - OBJECTIVE: To evaluate coronary artery atherosclerotic plaque characteristics and
      changes post coronary stenting by optical coherence tomography (OCT). METHODS:
      OCT images were obtained in 22 diseased coronary vessels after coronary
      angiography or percutaneous coronary interventions (PCI) in 20 patients and in 23
      stents [7 sirolimus-eluting stents (SES) follow up at 4-29 months post stenting
      and 8 bare mental stents (BMS) at 4-35 months post stenting, 8 stents immediately
      after PCI]. RESULTS: All 22 vessels and 23 stents OCT images were successfully
      acquired. Two thromboses, 8 fibrous, 9 lipid-rich and 3 calcium plaques as well
      as 3 plaque ruptures were visualized by OCT. No significant neointimal
      proliferation and restenosis were found in SES stents and some struts were not
      covered with neointima even at 29 months post stenting. Significant neointimal
      proliferation on surfaces of stent struts were visualized in all 8 BMS stents and
      restenosis was detected in 3 BMS stents. OCT images obtained immediately after
      PCI showed that 3 stents were well positioned, tissue prolapse between coronary
      stent struts occurred in 4 stents and stent dissociation with vessel wall could
      be seen in 1 stent. CONCLUSIONS: OCT imaging can clearly visualize different
      types of atherosclerotic plaques. By providing detailed information on plaque
      characteristics, this technique might help cardiologists in choosing suitable
      stents and guiding preventive therapy for patients with coronary heart disease.

PMID- 16626580
TI  - [Early ST resolution after successful primary PCI is related to a favorable
      outcome in ST elevated AMI patients].
AB  - OBJECTIVE: To analyze the relationship between the early ST resolution magnitude
      and TIMI flow, MACE and the cardiac function in ST elevated AMI (STEMI) patients
      after successful primary PCI. METHODS: A total of 120 consecutive patients with
      STEMI underwent primary PCI within 12 hours after the onset of chest pain were
      enrolled in this study, the ST segment resolution was calculated and the patients
      were divided into group A (n = 81, Sigma STE resolved > or = 50%) and group B (n
      = 39, Sigma STE resolved < 50%). TIMI flow after PCI, clinical events up to 30
      days post PCI and cardiac function 30 days post PCI were assessed. RESULTS: LVEF
      was higher in group A than that of group B (58.6% +/- 7.1% vs. 50.5% +/- 7.1%, P
      < 0.05). There are fewer patients with Killip III and IV in group A than in group
      B (1.2% vs. 12.8%, P < 0.05). The incidence of in-hospital MACE was also
      significantly less in group A than in group B (0 vs. 7.7%, P < 0.001). As
      expected, there were more patients with TIMI 3 flow (95.1% vs. 79.5%, P < 0.05)
      and fewer TIMI 2 (4.9% vs. 20.5%, P < 0.05) flow post PCI in group A than in
      group B and all 3 patients with MACE were group B patients with TIMI 2 flow.
      CONCLUSION: Early ST resolution post PCI represents improved myocardial perfusion
      and function and is related to a favorable clinical outcome in STEMI patients.

PMID- 16626581
TI  - [Glucose level on admission and outcome after primary percutaneous coronary
      intervention in patients with acute myocardial infarction].
AB  - OBJECTIVE: To investigate the influence of elevated glucose level on
      epicardial/microvascular flow and survival in patients with acute ST-segment
      elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (PCI). METHODS: A total of 308 patients with STEMI
      underwent primary PCI were divided into 3 groups according to the glucose level
      on admission: group 1, < 7.8 mmol/L; group 2, 7.8-11.0 mmol/L, and group 3, > or
      = 11.0 mmol/L. RESULTS: Compared with group 1, patients in the group 2 and 3 were
      older, had higher triglycerides levels and more 2-vessel or 3-vessel diseases.
      Although TIMI flow after PCI were similar among groups (89.7%, 86.0% and 86.3%, P
      = > 0.05), corrected TIMI frame count (CTFC) in group 2 and group 3 were higher
      than that in group 1. Moreover, TIMI myocardial perfusion grade (TMPG) 0-1 grade
      rate post PCI was higher in group 2 and 3 (30.3% and 29.0%) than that of group 1
      (17.3%, P < 0.05). There was less frequently complete ST-segment resolution
      (56.7%) and early T wave inversion (58.3%) in group 3 than that of group 1 after
      PCI (72.0% and 73.4% respectively, P < 0.05). Mortality rate at 30 days post PCI
      was significantly higher in the group 3 (10.4%) than that in the group 1 (2.6%, P
      < 0.05). CONCLUSION: Elevated glucose level on admission in ST-segment elevation
      myocardial infarction patients treated with primary PCI is associated with
      reduced myocardial microvascular flow. Abnormal myocardial microvascular flow
      might contribute to the poor outcomes observed in patients with hyperglycemia on
      admission.

PMID- 16626582
TI  - [Alpha-galactosidase A gene mutation in a Chinese family with Fabry disease
      mimicking clinical features of hypertrophic cardiomyopathy].
AB  - OBJECTIVE: To screen gene mutation in alpha-galactosidase A (alpha-Gal A) in a
      nonconsanguineous Chinese family with Fabry disease (FD) with clinical
      manifestations similar to hypertrophic cardiomyopathy (HCM). METHODS: Mutation
      analysis was performed by using purified PCR products to direct sequence analysis
      on an ABI-377XL automated DNA sequencer. DNA analysis of alpha-Gal A gene and
      physical and clinical examinations were performed in a female proband and in her
      relatives (15 subjects in total). RESULTS: Three hemizygotes and 6 heterozygotes
      were diagnosed for FD by the alpha-Gal A gene analysis with a missense mutation
      in exon 5 of the alpha-Gal A sequence, leading to a TGG32TGA substitution, which
      may induce the absent of tryptophan's translation (corresponded to TGG) by the
      terminator codon TGA. Six patients in the family were revealed as HCM by
      echocardiography. CONCLUSIONS: Present results show that it is important to
      differentiate FD from other causes of hypertrophy in patients with cardiac
      hypertrophy. Screening for alpha-Gal A gene mutations in patients with FD and in
      their relatives could help to identify all suspected cases within the families.

PMID- 16626584
TI  - [Increased lectin-like oxidized low density lipoprotein receptor-1 expression in
      the autologous vein grafts and vein graft atherosclerosis].
AB  - OBJECTIVE: To study the changes of lectin-like oxidized low density lipoprotein
      receptor-1 (LOX-1) expression in the autologous vein grafts and vein graft
      atherosclerotic lesions. METHODS: Thirty New Zealand white rabbits were randomly
      assigned to normal control group (rabbits fed with normal diet, n = 10), vein
      graft group (autologous external jugular vein grafting to common carotid artery
      and fed with normal diet, n = 10) or vein graft plus high-lipid diet group
      (autologous vein graft and fed with high-lipid diet, n = 10) for 12 weeks. LOX-1
      expressions in the grafts were examined by immunohistochemistry and semi
      quantitative reverse transcription-PCR. The relationships between serum total
      cholesterol level, intimal thickness and LOX-1 expression were also investigated.
      RESULTS: LOX-1 expression was low in the endothelium of external jugular veins in
      the normal control group and significantly increased in the endothelium and
      neointima of vein grafts in the vein graft group (0.31 +/- 0.14 vs. 0.09 +/-
      0.04, P < 0.01) and which was further increased in the endothelium and
      atherosclerotic lesions in the vein graft plus high-lipid diet group (0.93 +/-
      0.34 vs. 0.31 +/- 0.14, P < 0.01). LOX-1 expression in the atherosclerotic
      lesions was located both in endothelial cells and foam cells and the expression
      was most prominent in endothelial cells. LOX-1 expression and intimal thickness
      were positively related to serum total cholesterol level (P = 0.00 and 0.02) and
      the partial correlation coefficient was 0.78 and 0.42, respectively. CONCLUSIONS:
      LOX-1 expression is increased in endothelium and neointima of autologous vein
      grafts of rabbits. Hypercholesterolemia upregulates LOX-1 expression in vein
      graft atherosclerosis. Thus, LOX-1 might play an important role in the
      pathogenesis of vein graft atherosclerosis.

PMID- 16626585
TI  - [Heme oxygenase-1 and carbon monoxide are key mediators for vascular smooth
      muscle cells proliferation induced by insulin-like growth factor-I].
AB  - OBJECTIVE: To determine the role and related mechanisms of heme oxygenase
      1/carbon monoxide (HO-1/CO) on VSMCs proliferation induced by insulin-like growth
      factor-I (IGF-I). METHODS: VSMCs isolated from rabbit aorta were cultured in
      vitro and proliferation was induced by IGF-I. Hemin (a substrate and inducer of
      HO-1) or zinc protoporphyrin-IX (Znpp-IX, an inhibitor of HO-1) was added to
      stimulate or inhibit the expression of HO-1. The mRNA and protein expressions of
      HO-1 were detected by RT-PCR and Western blot analysis. CO released into the
      culture media was quantitated by measuring carbon monoxide hemoglobin (COHb),
      VSMCs proliferation and cell cycle were determined by (3)H-TdR incorporation
      assay and flow cytometry, respectively. RESULTS: The HO-1 mRNA and protein
      expressions in VSMCs and the amount of COHb in the culture media were
      significantly increased and the IGF-I-induced (3)H-TdR incorporations of VSMCs
      significantly reduced by hemin in a dose-dependent manner (P < 0.01).
      Furthermore, VSMCs in the G(0)/G(1) phase were increased and in the S and G(2)/M
      phase decreased by hemin (P < 0.01). Opposite results were observed in VSMCs
      treated with Znpp-IX. CONCLUSIONS: Endogenous HO-1 and CO are important mediators
      for inhibiting IGF-I induced VSMCs proliferation by reducing VSMCs DNA synthesis
      and decelerating cell cycle progression.

PMID- 16626587
TI  - [Gene transfer of CD151 enhanced myocardial angiogenesis and improved cardiac
      function in rats with experimental myocardial infarction].
AB  - OBJECTIVE: To investigate the effects of in vivo CD151 gene transfer on
      angiogenesis and heart function in rats with myocardial infarction. METHODS:
      Acute myocardial infarction (AMI) was induced in male Sprague-Dawley (SD) rats by
      left anterior descending coronary artery ligation. The surviving rats randomly
      received myocardial injection of saline (MI control), pAAV-CD151 and pAAV-GFP (n
      = 12/group). Sham-operated rats without myocardial injection (n = 12) were taken
      as normal control. Four weeks later, heart function and the expression of CD151
      were measured. Micro vessels density (MVD) in infarct myocardium was observed by
      factor VIII related antigen immunochemical staining. RESULTS: The expression of
      CD151 (1.98 +/- 0.23 vs. 0.91 +/- 0.09, P < 0.01) and MVD counting [(385.4 +/-
      79.9) vs. (252.5 +/- 43.0) n/mm(2), P < 0.01] in pAAV-CD151 treated MI rats were
      significantly higher than that in MI control group, similarly, EF (64.0 +/- 8.7)%
      vs. (41.5 +/- 5.0)%, P < 0.01] and dp/dt(max) (6620.2 +/- 884.6 vs. 5545.5 +/-
      693.0, P < 0.01) were also significantly increased post pAAV-CD151 treatment.
      These parameters were not affected by pAAV-GFP treatment. CONCLUSION: CD151 in
      vivo gene transfer for rats with acute myocardial infarction enhanced myocardial
      angiogenesis and improved left ventricular function.

PMID- 16626588
TI  - [The acute electrophysiological effects of amiodarone on normal and hypertrophied
      rat myocytes].
AB  - OBJECTIVE: The aim of the present study was to investigate the acute action of
      amiodarone (AM) on the inward currents I(Na), I(Ca-L) and outward currents I(k),
      I(k1), I(to) in hypertrophied and normal rat ventricular myocytes. METHODS: The
      pressure overload hypertrophy rat model was established by partial ligation of
      ascending aorta for 4 weeks. Ventricular myocytes were exposed to 0.01, 0.1, 1,
      10 and 50 micromol/L AM and whole cell patch clamp technique was used to study
      the acute effects of AM on the inward currents I(Na), I(Ca-L) and outward
      currents I(k), I(k1), I(to). RESULTS: (1) Compared with the normal ventricular
      myocytes, the current density of I(k), I(ks), I(to) and I(k1) were all decreased
      in hypertrophied myocytes, but I(Na) and I(Ca-L) remained unchanged. (2) I(Ca-L)
      was blocked by 59.0% +/- 4.4% in normal myocytes but only blocked by 16.7% +/-
      8.0% in hypertrophied myocytes after 50 micromol/L AM application; IC(50) of
      I(Na) were 9.2 micromol/L and 5.9 micromol/L in normal and in hypertrophied
      myocytes, respectively; I(to) was blocked by 55.9% +/- 5.5% in normal myocytes
      and 23.0% +/- 2.8% in hypertrophied myocytes after 50 micromol/L AM application.
      I(k1) was not affected by AM in both normal and hypertrophied myocytes; I(ks) was
      blocked by 21.6% +/- 5.6% in normal myocytes and 42.7% +/- 9.2% in hypertrophied
      myocytes after 10 micromol/L AM application. CONCLUSION: Our results show that
      the sensitivity of hypertrophied myocytes to AM on I(Na), I(ks) were higher than
      that of normal myocytes, while the sensitivity on I(Ca-L), I(k1), I(to) were
      lower than that of normal myocytes favoring the use of AM on hypertrophied
      myocardium for antiarrhythmic therapy.

PMID- 16626589
TI  - [Serum total cholesterol and 10-year cardiovascular risk in a Chinese cohort aged
      35-64 years].
AB  - OBJECTIVE: To evaluate the association between serum total cholesterol (TC) and
      the risk of cardiovascular diseases (CVD) in subjects aged 35-64 years. METHODS:
      This prospective study was performed from 1992 to 2002 in 11 provinces of China
      and the association between baseline TC level and the development of
      cardiovascular diseases was analyzed in 30 384 subjects aged 35-64 years using
      Cox multivariate proportional hazards regression. RESULTS: (1) Compared with the
      group of TC < 3.64 mmol/L (140 mg/dl), multivariate-adjusted relative risk of
      ischemic cardiovascular disease (ICVD, including CHD and ischemic stroke)
      increased continuously with increasing TC level. (2) TC level was positively
      related to the occurrence of ischemic stroke, but not to hemorrhagic stroke. The
      risk of CHD increased by 74% (RR = 1.743) and the risk of ischemic stroke
      increased by 12% (RR = 1.119) in the group with TC > or = 5.72 mmol/L compared
      with the group with TC < 5.72 mmol/L (220 mg/dl). (3) High serum cholesterol was
      responsible to 5.9% of ICVD, 11.7% of the acute CHD and 2.9% of the acute stroke.
      (4) At each TC level, the 10-year risk of ICVD increased in the presence of other
      risk factors. CONCLUSION: Starting from TC of 3.64 mmol/L, the risk of ICVD
      increases continuously with increasing TC level. Multiple risk factor
      intervention should be strengthened to reduce the overall risk of CVD.

PMID- 16626599
TI  - [Effect of abnormal neural innervation on hypertension].

PMID- 16626601
TI  - Marangoni instability and spontaneous non-linear oscillations produced at liquid
      interfaces by surfactant transfer.
AB  - The systems producing non-linear spontaneous oscillations of the interfacial
      tension and electric potential are considered and the available criteria for
      development of convective instability by the surfactant transfer through a liquid
      interface are discussed. The non-linear oscillations are observed by the
      surfactant transfer from a point-like source situated in the bulk of liquid, by
      the transfer of two ionic solutes through a liquid interface in two opposite
      directions, and by the transfer of ionic solutes through a liquid membrane. All
      these systems are governed by more complicated mechanisms than merely arising
      oscillatory convective instability. The main experimental results obtained for
      these three systems as well as theoretical models proposed for their explanation
      are discussed.

PMID- 16626602
TI  - Circulating cell-free fetal messenger RNA levels after fetoscopic interventions
      of complicated pregnancies.
AB  - OBJECTIVE: The aim of this study was to examine fetal gene expression in maternal
      plasma after fetoscopic intervention for twin-twin transfusion syndrome or
      congenital diaphragmatic hernia. STUDY DESIGN: Twelve women with pregnancies that
      were complicated by twin-twin transfusion syndrome and 10 women carrying fetuses
      with congenital diaphragmatic hernia were sampled before and sequentially after
      treatment. Levels of glyceraldehyde-3-phosphate dehydrogenase, human placental
      lactogen, and gamma globin messenger RNA were measured by real-time reverse
      transcriptase polymerase chain reaction amplification. RESULTS: At all time
      points, glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels were higher
      in the congenital diaphragmatic hernia cases than in the twin-twin transfusion
      syndrome cases (P < .05), but during the immediate postoperative observation
      period, there were no significant changes in glyceraldehyde-3-phosphate
      dehydrogenase, human placental lactogen, or gamma globin messenger RNA levels in
      individual patients or patients who were grouped by procedure. CONCLUSION:
      Fetoscopic intervention of complicated pregnancies does not affect circulating
      fetal messenger RNA levels, which is in contrast to earlier observations that
      circulating fetal DNA levels increase after laser ablation for twin-twin
      transfusion syndrome. Plasma glyceraldehyde-3-phosphate dehydrogenase messenger
      RNA levels could be a potential novel biomarker for fetal trauma.

PMID- 16626603
TI  - On redefining shoulder dystocia and at-risk populations.

PMID- 16626605
TI  - Translating data to dialogue: how to discuss mode of delivery with your patient
      with twins.
AB  - OBJECTIVE: Patients are given options with regard to the mode of delivery with
      increasing frequency. The manner in which obstetricians frame the risk/benefit
      information can have dramatic impact on the ultimate decision made by the
      patient. STUDY DESIGN: Recently published epidemiologic data reported increased
      morbidity and mortality to the second twin on the basis of mode of delivery. In
      this analysis, the findings of the epidemiologic studies were translated from
      odds ratio into the number of cesarean deliveries that would be required to
      prevent an adverse outcome for the second twin. RESULTS: For gestations of > or =
      36 weeks, 97 cesarean deliveries would need to be performed to prevent a single
      serious morbidity or mortality in a second twin. This number is within the range
      needed to prevent uterine rupture associated with trial of labor following
      cesarean delivery (556) or morbidity related to vaginal breech delivery (167).
      CONCLUSION: Number needed to treat may be more useful than odds risk assessment
      in patient counseling.

PMID- 16626607
TI  - A double-blind, randomized, placebo-controlled phase III study of the safety of
      alvimopan in patients who undergo simple total abdominal hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety and efficacy
      of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in
      patients who undergo simple total abdominal hysterectomy. STUDY DESIGN: Women (n
      = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n =
      106) > or = 2 hours before the operation then twice daily for 7 days (hospital
      and home). Adverse events were monitored up to 30 days after the last dose of
      study drug was administered. Efficacy was assessed for 7 postoperative days.
      RESULTS: Overall, the most common adverse events were nausea, vomiting, and
      constipation; < 5% of patients discontinued use because of adverse events.
      Alvimopan significantly accelerated the time to first bowel movement (hazard
      ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22
      hours, with more frequent bowel movement and better bowel movement quality found
      in the treatment cohort. CONCLUSION: Alvimopan has a safety profile that is
      similar to that of placebo and provides significantly improved lower
      gastrointestinal recovery in women who undergo simple total abdominal
      hysterectomy.

PMID- 16626608
TI  - Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and
      fetal membranes.
AB  - OBJECTIVE: Urocortin 2 (UCN2) and urocortin 3 (UCN 3) are recently identified
      neuropeptides showing homology to corticotropin-releasing factor (CRF). In the
      present study, we evaluated their expression and localization in gestational
      tissues (placenta, decidua, fetal membranes), and their effect on placental
      adrenocorticotropic hormone secretion. STUDY DESIGN: The study was performed in a
      tertiary clinical care center. Tissues were obtained at first (n = 8; 8-11 weeks
      of pregnancy) and third (n = 8; 38-40 gestational weeks) trimester. The mRNA
      expression was evaluated by semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR); the cellular localization by immunohistochemistry; ACTH
      levels were measured in media collected from cultured placental villi. RESULTS:
      All tissues analyzed expressed UCN2 and UCN3 mRNA. UCN2 and UCN3 were localized
      in cytotrophoblast and syncytiotrophoblast cells; UCN2 was present in maternal
      and fetal vessels and in amniotic cells, while UCN3 was absent. Finally, UCN2 and
      UCN3 did not stimulate ACTH secretion. CONCLUSION: Gestational tissues
      differentially express UCN2 and UCN3 and, despite their homology to CRF, they did
      not stimulate placental ACTH secretion.

PMID- 16626609
TI  - Validation of a low-cost, liquid-based screening method for cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: The objective of the study was to validate a low-cost, liquid-based
      method for cervical cancer screening. STUDY DESIGN: We conducted a retrospective,
      split-sample comparison of 300 liquid-based cervical cytology samples from a
      group of 150 human immunodeficiency virus-seropositive women and 150 women from
      low-risk general gynecology clinics whose specimens were screened via standard
      liquid-based methodology as part of routine care. Residual samples from each
      specimen were used to prepare a slide using a novel, inexpensive manual membrane
      method of liquid-based cytology. These slides were screened by a cytotechnologist
      and abnormal cases were reviewed by a pathologist. Final diagnoses from the
      manual membrane method of liquid-based cytology slides were compared with the
      original diagnoses and available cervical biopsy data. RESULTS: There was good
      overall agreement between the manual membrane method of liquid-based cytology and
      original cytology diagnoses (76.3% agreement; kappa = 0.52, 95% confidence
      interval 0.44 to 0.59). Using available biopsy data to determine the accuracy of
      each method to identify high-grade squamous intraepithelial lesions, the manual
      membrane method of liquid-based cytology method was found to have a higher
      sensitivity (71.4% versus 57.1%) and lower specificity (82.1% versus 89.7%). The
      slightly higher referral rate to colposcopy using the manual membrane method of
      liquid-based cytology method was limited to women from the low-risk general
      gynecology clinics (16.7% versus 12.0%, P = .05). CONCLUSION: The low-cost manual
      membrane method of liquid-based cytology cervical cytology method is comparable
      with a standard commercial method. Consequently, it may be of value in
      alternative screening strategies in resource-limited settings.

PMID- 16626610
TI  - Communicating contraceptive effectiveness: A randomized controlled trial to
      inform a World Health Organization family planning handbook.
AB  - OBJECTIVE: The objective of the study was to compare 3 different approaches for
      increasing clients' understanding of contraceptive effectiveness. STUDY DESIGN:
      We randomized 900 reproductive-age women in India and Jamaica to 1 of 3 charts
      presenting pregnancy risk. RESULTS: The most important reason for choosing a
      contraceptive was how well it prevents pregnancy (54%) followed by few side
      effects (17%). At baseline, knowledge about contraceptive effectiveness was poor.
      About half knew oral contraceptive pills are more effective than condoms (46%)
      and intrauterine devices are more effective than injectables (50%). All 3 charts
      improved knowledge significantly (P < .01) for these 2 questions. No chart
      improved knowledge better than any other (P > .05). The chart ranking
      contraceptive methods on a continuum was judged slightly easier to understand
      than the other 2 charts. CONCLUSION: Only with accurate understanding of
      pregnancy risk can clients make informed choices. Our results have already
      informed a global handbook for family planning providers to use the chart ranking
      contraceptive methods on a continuum.

PMID- 16626611
TI  - Ureaplasma associated preterm birth: is there a clinical application?

PMID- 16626612
TI  - Meloxicam effectively inhibits preterm labor uterine contractions in a
      chronically catheterized pregnant sheep model: impact on fetal blood flow and
      fetal-maternal physiologic parameters.
AB  - OBJECTIVE: Preterm birth occurs in 5% to 10% of all pregnancies and is associated
      with considerable neonatal mortality and morbidity. Effective and safe drugs to
      prevent preterm labor are not currently available. We have hypothesized that the
      nonsteroidal anti-inflammatory drug meloxicam, a more selective cyclooxygenase-2
      inhibitor will successfully inhibit labor but avoid the complications associated
      with inhibition of cyclooxygenase-1. STUDY DESIGN: Preterm labor was induced in
      chronically catheterized sheep by RU486 administration. Animals were then
      randomized to receive maternal infusions of saline (n = 5) or meloxicam (n = 4)
      for 48 hours or until delivery when the animals were killed and tissues and blood
      samples collected. RESULTS: Maternal infusion of meloxicam inhibited uterine
      contractions, increasing contraction duration, and attenuating frequency and
      amplitude. Saline-treated animals progressed to delivery. Administration of
      meloxicam was not associated with any change in fetal or maternal blood gas
      status, osmolality, arterial pressure, heart rate, or fetal blood flows.
      CONCLUSION: Meloxicam may represent a potentially safe and effective tocolytic
      agent.

PMID- 16626613
TI  - Endometrial endometrioid carcinoma: a glimpse at the natural course.
AB  - OBJECTIVE: This study was undertaken to assess the natural course of endometrial
      endometrioid carcinoma by identifying untreated patients and those with a
      prolonged (>6 months) treatment delay. STUDY DESIGN: A chart review of 252
      patients with histologically confirmed endometrial endometrioid carcinoma was
      conducted and clinical data of untreated patients and those with a prolonged
      treatment delay were abstracted. RESULTS: Seven patients (3 untreated and 4 with
      prolonged treatment delay) were identified. Five had clinical stage I and 5 had
      well-differentiated tumors. The survival of the untreated patients ranged from 5
      to 59 months. Of the patients with prolonged treatment delay, 2 died more than 5
      years after diagnosis and 2 are alive more than 5 years after diagnosis.
      CONCLUSION: The lengthy survival of our patients seems to indicate that the
      natural progression course, even in untreated patients, may be very slow in
      endometrial endometrioid carcinoma with favorable prognostic factors.

PMID- 16626614
TI  - Optimal range of hemoglobin concentration in pregnancy.

PMID- 16626615
TI  - Does a "vanishing twin" affect first-trimester biochemistry in Down syndrome risk
      assessment?
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of spontaneous
      reduction in multifetal pregnancy on first-trimester maternal serum biochemistry.
      STUDY DESIGN: We evaluated first-trimester pregnancy associated plasma protein-A
      (PAPP-A) and free beta-human chorionic gonadotropin levels in singleton euploid
      pregnancies. Biochemical values in pregnancies with evidence of spontaneous
      reduction were compared to other singleton pregnancies. Mann-Whitney U, Student t
      test, Fisher exact test, and logistic regression analysis were used for
      statistical comparison. RESULTS: There were 41 cases (0.9%) of spontaneous
      reduction. Though spontaneous reduction was not associated with different levels
      of either analyte, reduction within 4 weeks was associated with higher levels of
      both PAPP-A (1.79 vs 1.18; P = .002) and free beta-hCG (1.28 vs 0.96; P = .03)
      compared with other pregnancies. Spontaneous reduction was associated with a
      higher frequency of PAPP-A >95th %ile (17.1 vs 4.7%; P = .003) and free beta-hCG
      >95th %ile (17.1% vs 5.0%; P = .004). Logistic regression identified independent
      associations between spontaneous reduction and both high PAPP-A and high free
      beta-hCG. CONCLUSION: Recent spontaneous reduction is associated with higher
      values of PAPP-A and free beta-hCG. These differences have the potential to
      affect risk assessment for fetal aneuploidy.

PMID- 16626616
TI  - Is birth weight modified during pregnancy? Using sibling differences to
      understand the impact of blood glucose, obesity, and maternal weight gain in
      gestational diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the extent to which blood
      glucose, obesity, and maternal weight gain explains differences in birth weight
      using offspring sibling pairs in gestational diabetes mellitus (GDM). STUDY
      DESIGN: A retrospective analysis of 90 women with at least 2 GDM pregnancies was
      conducted. A fixed effects model was used to examine differences between siblings
      of the same mother (within-women), and results were contrasted with a
      multivariable regression model that compared different mothers (between-women).
      RESULTS: Higher maternal weight gain was significantly associated with increased
      birth weight within mothers, but not between different women. Conversely,
      overweight status (body mass index [BMI] > or = 25) was significant between
      mothers, but not within an individual mother's pregnancies. One-hour postprandial
      glucose was significant between-mothers, with a weaker association within
      mothers. There was no association between fasting glucose and birth weight in
      either analysis. CONCLUSION: Controlling pregnancy weight gain may reduce
      offspring birth weight in individual women with GDM, while the association
      between high birth weight and elevated prepregnancy BMI may represent a
      predisposition to both characteristics.

PMID- 16626617
TI  - Cause and solutions to the polymerase chain reaction smear problem in genotyping.

PMID- 16626618
TI  - A protein recycling system for nuclear magnetic resonance-based screening of drug
      candidates.
AB  - A sample-treating system for nuclear magnetic resonance (NMR)-based interaction
      screening between drug candidates (small molecules) and a protein of interest was
      developed by applying high-performance liquid chromatography (HPLC) technology.
      The system prepares a test solution by mixing a (15)N-labeled protein solution
      and a solution of each candidate compound, loads it to a flow cell-type NMR
      probe, and recycles the protein after the data acquisition. The system was
      designed to behave differently according to the information obtained in NMR
      measurements. In a test operation with a 100-compound library, the system could
      single out known interacting substances properly. Recovery values of the protein
      and one representative compound were 75 and 71%, respectively, and the recovered
      protein was found intact as intended.

PMID- 16626619
TI  - Optical detection of DNA hybridization based on fluorescence quenching of tagged
      oligonucleotide probes by gold nanoparticles.
AB  - A novel system for the detection of DNA hybridization in a homogeneous format is
      developed. This method is based on fluorescence quenching by gold nanoparticles
      used as both nanoscaffolds for the immobilization of capture sequences and
      nanoquenchers of fluorophores attached to detection sequences. The
      oligonucleotide-functionalized gold nanoparticles are synthesized by derivatizing
      the colloidal gold solution with 5'-thiolated 12-base oligonucleotides.
      Introduction of sequence-specific target DNAs (24 bases) into the mixture
      containing dye-tagged detection sequences and oligonucleotide-functionalized gold
      nanoparticles results in the quenching of carboxytetramethylrhodamine-labeled DNA
      fluorescence because DNA hybridization occurs and brings fluorophores into close
      proximity with oligonucleotide-functionalized gold nanoparticles. The quenching
      efficiency of fluorescence increases with the target DNA concentration and
      provides a quantitative measurement of sequence-specific DNA in sample. A
      linearity is obtained within the range from 1.4 to 92 nM. The target sequence is
      detected down to 2 nM. This new system not only overcomes many of the drawbacks
      inherent in radioisotopic measurement or enzyme-linked assay but also avoids the
      requirement for the stem-loop structure compared with conventional molecular
      beacons. Furthermore, the background signal that is defined as fluorescence
      quenching arising from electrostatic attraction between positively charged
      fluorophores and negatively charged gold nanoparticles is comparatively low due
      to electrostatic repulsion between negatively charged oligonucleotides. In
      addition, this is a homogeneous assay that can offer the potential to be
      monitored in real time, be amenable to automation, eliminate washing steps, and
      reduce the risk of contamination.

PMID- 16626620
TI  - [Left colon necrosis after endoscopic para-aortic lymph node exploration in a
      cervical carcinoma stage IIB].
AB  - Authors report a left colon ischemia six days after laparoscopic para-aortic
      lymphadenectomy in the staging of advanced cervical carcinoma. Before surgery,
      positron emission tomography scanning was performed: there were no para-aortic
      nodal metastasis. The histologic examination confirmed the radiological staging.
      Positron emission tomography scanning could avoid surgery in the case of patients
      with high risks morbidity factors.

PMID- 16626621
TI  - [Hydatic cyst of thyroid gland].
AB  - INTRODUCTION: Primary hydatid cyst of thyroid gland is an exceptional
      localization. The thyroid gland is an uncommon site even in Morocco where
      echinococcal disease is endemic. The aim of this study was to report our
      experience of this rare disease, and to review diagnosis problems and management.
      PATIENTS AND METHOD: Retrospective study of six patients with primary hydatid
      cyst of thyroid gland during a 4-year period. RESULTS: We report six cases of
      primary hydatid cyst of thyroid gland. Symptoms were isolated thyroid nodules.
      Diagnosis was based on echography and echinococcal immunologic test. However,
      hydatic origin was suspected in only 50% of patients preoperatively and
      immunologic test had 33% false positive rate. Surgical management was a lobo
      isthmectomy with a total resection of the cyst in four cases (67%) and a
      resection of the cyst prominent dome in two cases (33%). Diagnosis was always
      confirmed by macroscopic aspects and pathology. In all cases, the postoperative
      course was uneventful and no recurrence occurred with a 19 months follow up.
      CONCLUSION: Primary hydatid cyst of thyroid gland is a potential but rare
      situation. Positive diagnosis can be difficult during preoperative period. Cyst
      size and diagnosis doubt are two crucial criteria to decide the optimal surgical
      strategy (lobo-isthmectomy with total cyst resection vs resection of the cyst
      prominent dome).

PMID- 16626622
TI  - [Princeps procedure of gastric bypass for morbid obesity].
AB  - Princeps procedure of gastric bypass for morbid obesity is briefly described in
      this article including the three main steps: Roux-en-Y intestinal loop, gastric
      pouch and gastrojejunal anastomosis.

PMID- 16626623
TI  - The MAP kinase ERK5 binds to and phosphorylates p90 RSK.
AB  - We showed previously that p90 RSK was activated in cells expressing an activated
      mutant of MEK5, the activator of the MAP kinase ERK5. Based on the following
      evidence, we suggest that ERK5 can directly activate RSK in cells. ERK5 binds to
      RSK in vitro and co-immunoprecipitates from cell extracts; activation of ERK5
      weakens its binding to RSK, suggesting that RSK is released upon activation.
      Phosphorylation of RSK by ERK5 in vitro causes its activation, indicating that
      RSK is a substrate of ERK5. In cells activation of ERK5 but not p38 or the c-Jun
      N-terminal kinase is associated with RSK activation. The large C-terminal domain
      of ERK5 is not required for binding or activation of RSK by ERK5; however, the
      common docking or CD domain of ERK5 and the docking or D domain of RSK are
      important for their association.

PMID- 16626624
TI  - A new automated technique for the reconstitution of hydrophobic proteins into
      planar bilayer membranes. Studies of human recombinant uncoupling protein 1.
AB  - Electrophysiological characterisation of the vast number of annotated channel and
      transport proteins in the postgenomic era would be greatly facilitated by the
      introduction of rapid and robust methods for the functional incorporation of
      membrane proteins into defined lipid bilayers. Here, we describe an automated
      technique for reconstitution of membrane proteins into lipid bilayer membranes,
      which substantially reduces both the reconstitution time and the amount of
      protein required for the membrane formation. The method allows the investigation
      of single protein channels as well as insertion of multiple copies (approximately
      10(7)) into a single bilayer. Despite a comparatively large membrane area (up to
      300 microm diameter), the high stability of the membrane permits the application
      of transmembrane voltages up to 300 mV. This feature is especially important for
      studies of inner membrane mitochondrial proteins, since they act at potentials up
      to approximately 200 mV under physiological conditions. It is a combination of
      these advantages that enables the detailed investigation of the minuscule single
      protein conductances typical for proton transporters. We have applied the new
      technique for the reconstitution and electrophysiological characterisation of
      human recombinant uncoupling protein 1, hUCP1, that has been overexpressed in E.
      coli and purified from inclusion bodies. We demonstrate that hUCP1 activity in
      the presence of fatty acids is comparable to the activity of UCP1 isolated from
      brown adipose tissue.

PMID- 16626625
TI  - Properties of the permeability transition in VDAC1(-/-) mitochondria.
AB  - Opening of the permeability transition pore (PTP), a high-conductance
      mitochondrial channel, causes mitochondrial dysfunction with Ca2+ deregulation,
      ATP depletion, release of pyridine nucleotides and of mitochondrial apoptogenic
      proteins. Despite major efforts, the molecular nature of the PTP remains elusive.
      A compound library screening led to the identification of a novel high affinity
      PTP inhibitor (Ro 68-3400), which labeled a approximately 32 kDa protein that was
      identified as isoform 1 of the voltage-dependent anion channel (VDAC1) [A.M.
      Cesura, E. Pinard, R. Schubenel, V. Goetschy, A. Friedlein, H. Langen, P. Polcic,
      M.A. Forte, P. Bernardi, J.A. Kemp, The voltage-dependent anion channel is the
      target for a new class of inhibitors of the mitochondrial permeability transition
      pore. J. Biol. Chem. 278 (2003) 49812-49818]. In order to assess the role of
      VDAC1 in PTP formation and activity, we have studied the properties of
      mitochondria from VDAC1(-/-) mice. The basic properties of the PTP in VDAC1(-/-)
      mitochondria were indistinguishable from those of strain-matched mitochondria
      from wild-type CD1 mice, including inhibition by Ro 68-3400, which labeled
      identical proteins of 32 kDa in both wild-type and VDAC1(-/-) mitochondria. The
      labeled protein could be separated from all VDAC isoforms. While these results do
      not allow to exclude that VDAC is part of the PTP, they suggest that VDAC is not
      the target for PTP inhibition by Ro 68-3400.

PMID- 16626626
TI  - Mitochondrial dysfunction in patients with severe sepsis: an EPR interrogation of
      individual respiratory chain components.
AB  - Electron paramagnetic resonance (EPR) spectra of complex biological systems
      contain information about the paramagnetic centres present. Retrieving such
      information is important since paramagnetic species are common intermediates of
      all redox reactions in both normal and abnormal metabolism. However, it is often
      difficult to determine the nature and content of all paramagnetic species present
      because the EPR signals from individual centres overlap. Here, we apply our
      deconvolution method based on spectra subtraction with variable coefficient to
      quantify individual paramagnetic components of human muscle biopsies taken from
      critically ill patients with severe sepsis. We use low temperature EPR
      spectroscopy to identify and quantify nine different paramagnetic species in the
      tissue. These include the majority of the mitochondrial iron-sulfur centres and
      the first in vivo report of a mitochondrial radical assigned to a spin-coupled
      pair of semiquinones (SQ*-SQ*). We have previously demonstrated in these same
      muscle biopsies that biochemical assays of mitochondrial dysfunction correlate
      with clinical outcomes (D. Brealey, M. Brand, I. Hargreaves, S. Heales, J. Land,
      R. Smolenski, N.A. Davies, C.E. Cooper, M. Singer, Association between
      mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360
      (2002) 219-223.). Analysis of the paramagnetic centres in the muscle confirms and
      extends these findings: the (SQ*-SQ*) radical species negatively correlates with
      the illness severity of the patient (APACHE II score) and a decreased
      concentration of mitochondrial Complex I iron-sulfur redox centres is linked to
      mortality.

PMID- 16626627
TI  - Lateral energy transfer model for adjacent light-harvesting antennae rods of C
      phycocyanins.
AB  - Modeling of excitation transfer pathways have been carried out for the structure
      of Spirulina platensis C-phycocyanin. Calculations by Forster mechanism using the
      crystal structure coordinates determined in our laboratory indicate ultra-fast
      lateral energy transfer rates between pairs of chromophores attached to two
      adjacent hexamer disks. The pairwise transfer times of the order of a few pico
      seconds correspond to resonance transitions between peripheral beta155
      chromophores. A quantitative lateral energy transfer model for C-phycocyanin
      light-harvesting antenna rods that is suggestive to its native structural
      organization emerges from this study.

PMID- 16626628
TI  - Antimicrobial activity of an abiotic host defense peptide mimic.
AB  - Bacterial drug resistance is emerging as one of the most significant challenges
      to human health. Antimicrobial peptides (AMPs), which are produced by many
      tissues and cell types of invertebrates, insects, and humans, as part of their
      innate immune system, have attracted considerable interest as alternative
      antibiotics. Interest in novel mimics of AMPs has increased greatly over the last
      few years. This report details a new AMP mimic, based on phenylene ethynylene,
      with improved antimicrobial activity and selectivity. Screening against a large
      set of bacterial and other organisms demonstrates broad spectrum antimicrobial
      activity including activity against antibiotic resistant bacterial like
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      Enterococci (VRE) as well as activity against yeast (Candida albicans) and fungus
      (Stachybotrys chartarum). Bacterial resistance development studies using
      Staphylococcus aureus show a rapid increase in MIC for conventional antibiotics,
      ciprofloxacin and norfloxacin. In sharp contrast, no change in MIC was observed
      for the AMP mimic. Cytotoxicity experiments show that the AMP mimic acts
      preferentially on microbes as opposed to mammalian red blood cells, 3T3
      fibroblasts, and HEPG2 cells. In vivo experiments determined the maximum
      tolerated dose (MTD) to be 10 mg/kg suggesting a therapeutic window is available.
      These studies indicate that nonpeptidic amphiphilic AMP mimics could be developed
      as potential new treatments for antibiotic-resistant bacterial infections.

PMID- 16626629
TI  - Nystatin-induced lipid vesicles permeabilization is strongly dependent on sterol
      structure.
AB  - The selectivity of the antibiotic nystatin towards ergosterol compared to
      cholesterol is believed to be a crucial factor in its specificity for fungi. In
      order to define the structural features of sterols that control this effect,
      nystatin interaction with ergosterol-, cholesterol-, brassicasterol- and 7
      dehydrocholesterol-containing palmitoyloleoylphosphocholine vesicles was studied
      by fluorescence spectroscopy. Variations in sterol structure were correlated with
      their effect on nystatin photophysical and activity properties. Substitution of
      cholesterol by either 7-dehydrocholesterol or brassicasterol enhance nystatin
      ability to dissipate a transmembrane K+ gradient, showing that the presence of
      additional double bonds in these sterols-carbon C7 and C22, plus an additional
      methyl group on C-24, respectively-as compared to cholesterol, is fundamental for
      nystatin-sterol interaction. However, both modifications of the cholesterol
      molecule, like in the fungal sterol ergosterol, are critical for the formation of
      very compact nystatin oligomers in the lipid bilayer that present a long mean
      fluorescence lifetime and induce a very fast transmembrane dissipation. These
      observations are relevant to the molecular mechanism underlying the high
      selectivity presented by nystatin towards fungal cells (with ergosterol) as
      compared to mammalian cells (with cholesterol).

PMID- 16626630
TI  - Raft-like domain formation in large unilamellar vesicles probed by the
      fluorescent phospholipid analogue, C12NBD-PC.
AB  - The liquid-ordered/disordered-phase domain co-existence in large unilamellar
      vesicle membranes consisting of phosphatidylcholine:sphingomyelin (2:1) with
      different amounts of cholesterol has been examined using a concentration
      dependent self-quenching of a single reporter molecule, C12NBD-PC. A temperature
      dependent decrease of fluorescence intensity was associated with the expected
      formation and increase of l(o)-phase membrane fraction in the vesicles. The
      result is consistent with exclusion of the fluorescent probe from the liquid
      ordered phase which partitions preferentially into the liquid-disordered phase
      membrane domains. This leads to an increase of the local concentration of
      fluorophore in the liquid-disordered phase and a decrease of the quantum yield.
      This effect was used to obtain a quantitative estimation of the fraction of the
      vesicle membrane occupied by the liquid-ordered phase, Phi(o), as a function of
      temperature and cholesterol content between 0 and 45 mol%. The value of Phi(o)
      was related to the assumed partition coefficient k(p) of probe between liquid
      ordered/disordered phases. For large unilamellar vesicles containing 20 and 4
      mol% cholesterol and probe, respectively, with k(p) = 0 (probe completely
      excluded from liquid-ordered phase), Phi(o) = 0.16 and with k(p) = 0.2, Phi(o) =
      0.2. The results are relevant to the action of detergent in the fractionation of
      detergent-resistant membrane from living cells.

PMID- 16626631
TI  - AFM study of interaction forces in supported planar DPPC bilayers in the presence
      of general anesthetic halothane.
AB  - In spite of numerous investigations, the molecular mechanism of general
      anesthetics action is still not well understood. It has been shown that the
      anesthetic potency is related to the ability of an anesthetic to partition into
      the membrane. We have investigated changes in structure, dynamics and forces of
      interaction in supported dipalmitoylphosphatidylcholine (DPPC) bilayers in the
      presence of the general anesthetic halothane. In the present study, we measured
      the forces of interaction between the probe and the bilayer using an atomic force
      microscope. The changes in force curves as a function of anesthetic incorporation
      were analyzed. Force measurements were in good agreement with AFM imaging data,
      and provided valuable information on bilayer thickness, structural transitions,
      and halothane-induced changes in electrostatic and adhesive properties.

PMID- 16626632
TI  - Cognitive variables related to worry among adolescents: avoidance strategies and
      faulty beliefs about worry.
AB  - Studies aiming to better understand worry have neglected children and
      adolescents. This constitutes an important limitation considering that excessive
      worry is frequent among adolescents and that patients suffering from excessive
      worries associate the beginning of their disorder with adolescence. This study
      evaluates the cognitive variables associated with worry in a sample of 777
      adolescents. It attempts to determine whether cognitive avoidance and false
      beliefs about the usefulness of worries are present and associated with worries
      in adolescence. The results showed that participants with a high level of worry
      used more avoidance strategies and held more beliefs about worry. The results
      also revealed that avoidance of stimuli that trigger unpleasant thoughts and
      thought substitution were the major avoidance strategies related to worry among
      adolescents. The belief that worry helps to avoid future negative events was also
      related to worry. These findings may suggest that adolescents' worries are
      maintained by processes similar to those observed among adults.

PMID- 16626633
TI  - Expression of amino acid receptors and neural peptides in the weaver mouse brain.
AB  - In the present study, we conducted: (i) in situ hybridization in order to
      investigate the expression of kainate and GABA(A) receptor subunits and the pre
      proenkephalin and prodynorphin peptides in the brain of weaver mouse (a genetic
      model of dopamine deficiency) and (ii) immunocytochemistry in order to study the
      somatostatin-positive cells in weaver striatum. Our results indicated: (i)
      increases in mRNA levels of KA2 and GluR6 kainate receptor subunits, of alpha(4)
      and beta(3) GABA(A) receptor subunits and of pre-proenkephalin and prodynorphin
      in 6-month-old weaver striatum; (ii) a decrease in alpha(1) and beta(2) GABA(A)
      subunit mRNAs in 6-month-old weaver globus pallidus; (iii) increases in KA2,
      alpha(4) and beta(3) and decreases in alpha(2) and beta(2) mRNAs in the 6-month
      old weaver somatosensory cortex; and (iv) an increase in somatostatin
      immunopositive cells in 3-month-old weaver striatum. We suggest that: (i) in
      striatum, the alterations are induced by the induction of the transcription
      factor DeltafosB (for GluR6, pre-proenkephalin and prodynorphin mRNAs) and the
      suppression of transcription factors like NGF-IB (nerve growth factor inducible
      B; for the KA2 mRNA), in response to dopamine depletion; (ii) in striatum and
      cortex, the alterations in the expression of the GABA(A) subunits indicate an
      increase of extrasynaptic versus a decrease of synaptic GABA(A) receptors; and
      (iii) in globus pallidus, the increased striatopallidal GABAergic transmission
      leads to a decrease in the number of GABA(A) receptors. Our results further
      clarify the regulatory role of dopamine in the expression of amino acid receptors
      and striatal neuropeptides.

PMID- 16626634
TI  - Effects of spinal cord injury on c-fos expression in hypothalamic paraventricular
      nucleus and supraoptic nucleus in rats.
AB  - The effects of spinal cord injury (SCI) on c-fos expression in hypothalamic
      paraventricular nucleus (PVN) and supraoptic nucleus (SON) in rats were
      investigated. As hypothesized, SCI has a significant effect on neuronal responses
      in the PVN and SON. A significant increase in c-fos in the PVN was found at 1, 6,
      12 and 24 h following SCI, implying that the neurons in the PVN can be activated
      soon after SCI and persist for at least 24 h. However, in contrast to the PVN,
      SCI did not induce a significant increase in c-fos expression in the SON until 12
      h following SCI. The highest expression of c-fos in the SON was found at the end
      point of this study (24 h) following SCI. The data demonstrated that SCI can
      significantly activate neurons in the PVN and SON. The activated neurons might
      involve in the initiation of a variety biochemical, ischemic and other injury
      processes. The area-specific effects of SCI on the PVN and SON suggest that these
      nuclei might play their roles in different stages in the prolonged time course
      following SCI.

PMID- 16626635
TI  - Shock stress protects mice against amphetamine-induced dopaminergic toxicity.
AB  - The effect of tail shock (ten, 2.0 mA/0.15 s shocks) on amphetamine-induced
      dopaminergic toxicity in adult, male BALB/c mice was assessed. Fifteen minutes
      following a single shock session, mice received amphetamine (50-mg/kg) or saline
      as follows: Shock/Saline; NoShock/Saline; Shock/Amphetamine; No
      Shock/Amphetamine. Amphetamine caused a 60% dopamine depletion in the No
      Shock/Amphetamine group. Tail shock provided neuroprotection against amphetamine
      induced dopamine depletion, an effect likely related to the stress response.

PMID- 16626636
TI  - Na+/Ca2+ exchanger 1 alters in pyramidal cells and expresses in astrocytes of the
      gerbil hippocampal CA1 region after ischemia.
AB  - Alterations of immunoreactivity and protein contents of Na(+)/Ca(2+) exchanger 1
      (NCX1) were observed in the gerbil hippocampus proper after 5 min of transient
      forebrain ischemia. NCX1 immunoreactivity was significantly changed in the
      hippocampal CA1 region, but not in the CA2/3 region after ischemia/reperfusion.
      In the sham-operated group, NCX1 immunoreactivity was mainly detected in CA1
      pyramidal cells. However, 30 min after ischemia/reperfusion, NCX1
      immunoreactivity was significantly decreased and then increased at 1 day after
      ischemia. At this time, NCX1 immunoreactivity in CA1 pyramidal cells was similar
      to that of the sham-operated group. At 3 days after ischemia, NCX1
      immunoreactivity was significantly reduced in the CA1 region compared to that of
      the sham-operated group and NCX1 immunoreactivity was significantly increased
      again 4 days after ischemia. Thereafter, NCX1 immunoreactivity was decreased time
      dependently in ischemia groups. Between 15 min and 6 h post-ischemia, NCX1
      immunoreactivity was expressed in astrocytes in the strata oriens and radiatum of
      the CA1 region. From 3 days post-ischemia, NCX1 immunoreactivity was expressed in
      astrocytes in the strata oriens and radiatum. Ischemia-induced changes in NCX1
      protein contents in the hippocampus proper concurred with immunohistochemical
      data post-ischemia. Our results suggest that changes in NCX1 in CA1 pyramidal
      cells and astrocytes after ischemia are associated with intracellular Na(+)
      concentrations and that NCX1 may induce an intracellular calcium overload, which
      may be related to neuronal death.

PMID- 16626637
TI  - On the retention of neurotensin in the ventral tegmental area (VTA) despite
      destruction of the main neurotensinergic afferents of the VTA--implications for
      the organization of forebrain projections to the VTA.
AB  - Neurotensin (NT) modulates ventral tegmental area (VTA) signaling in a manner
      relevant to psychostimulant drug actions, thus inviting evaluation of
      psychostimulant effects in conditions of reduced or absent VTA NT. However, in a
      preliminary study, NT immunoreactivity (-ir) in the VTA was unaffected following
      destruction of the main concentration of forebrain neurotensinergic VTA afferents
      in the lateral preoptic-rostral lateral hypothalamic continuum (LPH) and adjacent
      lateral part of the medial preoptic area (MPOA). This study attempted to
      determine what measures are necessary to obtain a significant reduction of VTA NT
      ir. Large unilateral ibotenic acid lesions were made in several structures
      containing NTergic, VTA-projecting neurons, including the LPH-MPOA, nucleus
      accumbens, VTA itself and dorsal raphe. None of these was associated with
      substantial ipsilateral loss of NT-ir in the VTA, lateral hypothalamus or lateral
      habenula. Combinations of lesions, such as LPH-MPOA plus VTA and LPH-MPOA plus
      dorsal raphe, also failed to substantially reduce NT-ir in these structures.
      Transections of the medial forebrain bundle (mfb) likewise failed to produce a
      substantial loss of VTA NT-ir measured with immunohistochemistry and
      radioimmunoassay. Transections of the mfb were carried out in combination with
      infusions of retrograde and anterograde axonal tract-tracers, revealing that the
      routes taken by some forebrain NT-ir VTA afferents circumvent mfb transections.
      All of these results together are consistent with the hypothesis that the
      connectional organization of forebrain and brainstem, potentially in combination
      with limited adaptive synaptogenesis, renders the VTA relatively insensitive to
      moderate losses of neurotensinergic and, perhaps, other peptidergic afferents.

PMID- 16626638
TI  - Chronic stress induces upregulation of brain-derived neurotrophic factor (BDNF)
      mRNA and integrin alpha5 expression in the rat pineal gland.
AB  - Chronic stress affects brain areas involved in learning and emotional responses.
      These alterations have been related with the development of cognitive deficits in
      major depression. Moreover, stress induces deleterious actions on the epithalamic
      pineal organ, a gland involved in a wide range of physiological functions. The
      aim of this study was to investigate whether the stress effects on the pineal
      gland are related with changes in the expression of neurotrophic factors and cell
      adhesion molecules. Using reverse transcription-polymerase chain reaction (RT
      PCR) and Western blot, we analyzed the effect of chronic immobilization stress on
      the BDNF mRNA and integrin alpha5 expression in the rat pineal gland. We found
      that BDNF is produced in situ in the pineal gland. Chronic immobilization stress
      induced upregulation of BDNF mRNA and integrin alpha5 expression in the rat
      pineal gland but did not produce changes in beta-actin mRNA or in GAPDH
      expression. Stressed animals also evidenced an increase in anxiety-like behavior
      and acute gastric lesions. These results suggest that BDNF and integrin alpha5
      may have a counteracting effect to the deleterious actions of immobilization
      stress on functionally stimulated pinealocytes. Furthermore, this study proposes
      that the pineal gland may be a target of glucocorticoid damage during stress.

PMID- 16626639
TI  - AMPA/kainate receptor-mediated up-regulation of GABAA receptor delta subunit mRNA
      expression in cultured rat cerebellar granule cells is dependent on NMDA receptor
      activation.
AB  - We have studied the effects of AMPA/kainate receptor agonists on GABA(A) receptor
      subunit mRNA expression in vitro in cultured rat cerebellar granule cells (CGCs).
      Kainate (KA) (100 microM) and high K(+) (25 mM) dramatically up-regulated delta
      subunit mRNA expression to 500-700% of that in control cells grown in low K(+) (5
      mM). KA or high K(+) had no effect on the expression of the other major GABA(A)
      receptor subunits alpha1, alpha6, beta2, beta3 or gamma2. Up-regulation of delta
      mRNA was also detected with the AMPA receptor-selective agonist CPW-399 and to a
      lesser extent with the KA receptor-selective agonist ATPA. AMPA/kainate receptor
      selective antagonist DNQX completely inhibited KA-, CPW-399- and ATPA-induced
      delta mRNA up-regulation indicating that the effects were mediated via AMPA and
      KA receptor activation. NMDA receptor-selective antagonist MK-801 inhibited 76%
      of the KA- and 57% of the CPW-399-induced delta up-regulation suggesting that KA
      and CPW-399 treatments may induce glutamate release resulting in NMDA receptor
      activation, and subsequently to delta mRNA up-regulation. In CGCs, delta subunit
      is a component of extrasynaptic alpha6betadelta receptors that mediate tonic
      inhibition. Up-regulation of delta during prolonged glutamate receptor activation
      or cell membrane depolarization may be a mechanism to increase tonic inhibition
      to counteract excessive excitation.

PMID- 16626640
TI  - Effects of chronic fenfluramine administration on hypothalamic neuropeptide mRNA
      expression.
AB  - Appetite suppressants lose efficacy when given chronically; the mechanisms are
      unknown. We gave male rats once-daily dl-fenfluramine (dl-FEN, 5 mg/kg, i.p.)
      injections for 15 days and measured mRNA expression of corticotropin releasing
      factor (CRF), neuropeptide Y (NPY) and proopiomelanocortin (POMC) in hypothalamic
      neurons on days 1, 2 and 15. dl-FEN decreased food intake on days 1-2 but not on
      day 15. The drug increased CRF mRNA and decreased NPY mRNA on days 1-2; on day
      15, NPY mRNA was normal, but CRF mRNA remained elevated. No changes occurred in
      POMC mRNA. Thus, only the NPY mRNA response to dl-FEN correlated with changes in
      food intake over time in a manner consistent with the known effects of NPY on
      food intake.

PMID- 16626641
TI  - Proximal colon distension induces Fos expression in the brain and inhibits
      gastric emptying through capsaicin-sensitive pathways in conscious rats.
AB  - We assessed brain nuclei activated during noxious mechanical distension of the
      proximal colon in conscious rats, using Fos as a marker of neuronal activation,
      and functional reflex changes in gastric emptying associated to colon distension.
      The role of capsaicin-sensitive afferents in Fos and gastric responses to
      distension was also investigated. Compared with sham distension, isovolumetric
      phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) increased
      significantly Fos expression 1 h after distension in selective brain areas, most
      prominently, the paraventricular and supraoptic nuclei of the hypothalamus (13
      fold and 80-fold, respectively), the locus coeruleus-Barrington's nucleus complex
      (2-fold), area postrema (7-fold) and the nucleus tractus solitarius (4-fold).
      Increased Fos expression was also observed in the cingulate cortex, posterior
      paraventricular nucleus of the thalamus, periaqueductal gray and ventrolateral
      medulla. Distension of the proximal colon significantly inhibited gastric
      emptying by 82% and 34%, as measured 30 and 60 min after the distension
      respectively, compared with control. Pretreatment with systemic capsaicin
      prevented both the brain increase in Fos expression and the inhibition of gastric
      emptying induced by the colon distension. These results show that visceral pain
      arising from the proximal colon activates a complex neuronal network that
      includes specific brain nuclei involved in the integration of autonomic,
      neuroendocrine and behavioral responses to pain and an inhibitory motor reflex in
      other gut areas (delayed gastric emptying). Capsaicin-sensitive afferent pathways
      are involved in mediating brain neuronal activation and functional changes
      associated with noxious visceral stimulation.

PMID- 16626642
TI  - GDNF abates serum deprivation-induced tyrosine hydroxylase Ser19 phosphorylation
      and activity.
AB  - High dopamine levels can contribute to neuronal dysfunction, impair plasticity
      and be toxic to neuronal cells in pathological conditions. The synthesis of
      dopamine is regulated by phosphorylation of the rate-limiting enzyme tyrosine
      hydroxylase (TH) under physiological conditions, with the phosphorylation of
      Ser31 and Ser40 directly increasing TH activity. Although a third phosphorylation
      site, Ser19, does not appear to directly regulate TH activity in physiological
      conditions, its role in pathological conditions is poorly understood. In this
      study, we examined the effects of serum deprivation (to mimic loss of
      retrogradely/anterogradely transported target-derived neurotrophic factors
      following axonal injury) and glutamate receptor stimulation (to mimic
      excitotoxicity) on TH phosphorylation and activity in a cell line and in
      mesencephalic primary culture cells. In addition, we also tested whether glial
      cell line-derived neurotrophic factor (GDNF) can alter these changes. We
      demonstrate that serum-deprivation resulted in a sustained increase in Ser19
      phosphorylation beginning at 3 h and lasting up to 10 h without any detectable
      change in Ser31 or Ser40 phosphorylation within this time frame. This increase in
      Ser19 phosphorylation was associated with enhanced TH activity and was due, in
      part, to glutamate-receptor-mediated calcium influx and possibly
      calcium/calmodulin-dependent protein kinase II (CaMKII) activation. Interestingly
      in this serum-deprivation model, GDNF blocked the increase in Ser19
      phosphorylation and TH activity at the 10-h time point following serum
      deprivation. Furthermore, GDNF also blocked the glutamate-mediated increase in
      Ser19 phosphorylation in rat primary mesencephalic neuronal cultures. Taken
      together, these findings suggest that GDNF may reduce dopamine synthesis in
      pathological conditions.

PMID- 16626643
TI  - Nicotinic receptor inactivation after acute and repeated in vivo nicotine
      exposures in rats.
AB  - Nicotine tolerance is often accompanied by an upregulation of brain area
      nicotinic acetylcholine receptors (nAChRs) in both animal and human subjects.
      This upregulation has been hypothesized to result from repeated or prolonged
      exposures of these receptors to nicotine. To explore this further, this study
      examined the level of nAChR desensitization following acute and repeated nicotine
      administration in the male Lewis rat. Nicotine-stimulated (86)Rb(+) efflux was
      measured in synaptosomes prepared from the frontal cortex, hippocampus, striatum,
      and thalamus. Analysis of receptor functionality was achieved by calculating area
      under-the-curve (AUC) for nicotine-induced fractional (86)Rb(+) efflux. Nicotine
      stimulated (86)Rb(+) efflux from all brain regions was significantly less in rats
      that received an acute injection of 0.4 mg/kg nicotine (s.c.) 15 min prior to
      dissection compared to control rats. This decrease in nAChR functional status was
      also observed in rats treated with 1 day or 14 days of twice-daily nicotine
      administration. These results are consistent with the concept that acute exposure
      to nicotine induces rapid desensitization of nAChRs. In addition, following
      repeated exposure to nicotine, nAChRs did not become tolerant to the loss in
      receptor function that occurs after an initial nicotine administration. Overall,
      these data suggest that neuronal adaptations underlying nicotine tolerance may
      begin upon initial exposure then persist following repeated exposures.

PMID- 16626644
TI  - The effects of neuronal induction on gene expression profile in bone marrow
      stromal cells (BMSC)--a preliminary study using microarray analysis.
AB  - Bone marrow stromal cells (BMSC) have been anticipated as a donor for cell type
      for transplantation therapy in various neurological disorders. However, their
      neurogenic capacity still remains undetermined. In this study, we aimed to
      clarify whether in vitro chemical treatment promotes their neuronal
      differentiation on the level of gene expression. Mice BMSC were cultured with
      medium supplemented with DMSO, retinoic acid, and basic fibroblast growth factor,
      and their morphology and expression of neuronal markers were evaluated.
      Subsequently, using microarray and RT-PCR techniques, the treatment-induced
      changes in the gene expression profile were analyzed. After exposure to the
      medium, the BMSC simulated a neuron-like appearance and increased their
      immunoreactivity for nestin and Tuj-1. Microarray analysis revealed that the BMSC
      per se express the multilineage cellular genes, including those associated with
      the neuron. Chemical treatment significantly decreased the expression of genes
      related to mesenchymal cells and increased the expression of 5 neuron-associated
      genes. Microarray and RT-PCR analyses also demonstrated that the BMSC express the
      genes for several growth factors including NGF-beta and BDNF, indicating their
      therapeutic role in protecting the injured central nervous system. The present
      results suggest that at least a certain subpopulation of the BMSC have the
      potential to alter their gene expression profile in response to the surrounding
      environment and may possibly protect the host tissue by secreting neuroprotective
      factors.

PMID- 16626645
TI  - Assessment of prestin self-association using fluorescence resonance energy
      transfer.
AB  - An active process within the cochlea is necessary to obtain the sensitivity and
      frequency selectivity characteristic of mammalian hearing. This process is
      realized, at least in part, through the electromotile response of outer hair
      cells (OHCs). Electromotility requires the presence of prestin, a transmembrane
      protein highly expressed in the OHC lateral wall. Very little is known about how
      prestin functions at the molecular level to elicit electromotility, but
      theoretical models and recent experiments suggest that prestin-prestin
      interactions are required. To explore the extent of proposed prestin
      interactions, we employ fluorescence resonance energy transfer (FRET). FRET is a
      powerful optical technique capable of measuring inter-fluorophore distances less
      than 10 nm. Using human embryonic kidney cells (HEKs) as a model cell system and
      the standard FRET pair, cyan fluorescent protein (CFP) as the donor and yellow
      fluorescent protein (YFP) as the acceptor, we assay for the self-association of
      prestin under steady-state conditions using acceptor photobleach FRET (apFRET)
      and sensitized emission FRET (seFRET). Our findings from apFRET indicate the
      presence of prestin self-association when HEKs express both prestin-CFP and
      prestin-YFP in the membrane. The average FRET efficiency was approximately 9%,
      but values as high as 20% were measured. Notably, a higher efficiency of energy
      transfer ranging from 10-30% was obtained with seFRET. Additionally, we report an
      apFRET efficiency of approximately 10% for cells expressing a CFP-prestin-YFP
      double fusion protein. We discuss the significance of these measurements for
      establishing the presence of prestin-prestin interactions in transfected HEK
      cells.

PMID- 16626646
TI  - Early life stress impairs fear conditioning in adult male and female rats.
AB  - We demonstrated that neonatal isolation (1-h pup isolation; postnatal days 2-9)
      impairs context-induced fear conditioning in adult male rats and tends to enhance
      this effect and foot shock sensitivity in females. In this study, we examine the
      effects of brief (i.e., handling; 15 min) and prolonged (3 h) maternal
      separations (postnatal days 1-21) on fear conditioning and foot shock sensitivity
      in adult male and female rats. Identical training and test conditions from our
      prior study were employed so comparisons of the three early life stressors could
      be made. Context- and cue-elicited freezing and ultrasonic vocalizations (USVs;
      22 kHz) were measured after 10 tone-shock training trials in Experiment 1. In
      Experiment 2, foot shock responses (flinch, jump, sonic vocalizations) to
      escalating shock levels were assessed. Brief maternal separation impaired context
      and cue-conditioned fear in rats of both sexes as assessed by USVs. Prolonged
      maternal separation only impaired context fear in female rats. There were no
      effects on foot shock sensitivity. Results of this and other studies suggest that
      early life stress impairs fear conditioning in adult rats whereas stress
      experienced in adulthood has the opposite effect. These opposing effects may
      reflect developmental differences on stress-induced alterations on hippocampal
      regulation of the hypothalamic-pituitary-adrenal axis.

PMID- 16626647
TI  - Differential distribution and regulation of galanin receptors- 1 and -2 in the
      rat lumbar spinal cord.
AB  - The expression of the galanin receptor-1 and -2 (Gal(1) and Gal(2)) messenger
      ribonucleic acids (mRNAs) was studied in the lower spinal cord of rat by means of
      in situ hybridization, using ribonucleic acid probes (riboprobes). Naive rats as
      well as rats with unilateral axotomy of the sciatic nerve or unilateral
      inflammation of the hindpaw were analyzed. In naive rats, numerous Gal(1) mRNA
      positive (+) neurons were detected in lamina (L) I-III. In addition, several
      Gal(1) mRNA(+) neurons were seen in deeper layers, including the ventral horns,
      area X, and the lateral spinal nucleus. In contrast, few and comparatively weakly
      labeled Gal(2) mRNA(+) neurons were observed, mostly in the ventral horns and in
      area X, with fewer in the dorsal horn and in the sympathetic and parasympathetic
      intermediate lateral cell columns. Axotomy induced a strong increase in intensity
      and number of Gal(2) mRNA(+) motoneurons ipsilateral to the lesion. In contrast,
      nerve cut or hindpaw inflammation did not alter the expression of Gal(1) or
      Gal(2) in the dorsal horn. The present (and previous) results suggest that
      galanin, acting through Gal(1) and Gal(2) receptors, has a modulatory role on
      spinal excitability, not only via interneurons in superficial dorsal horn, but
      also on neurons in deep layers and area X, as well as on the sympathetic and
      parasympathetic outflow. Furthermore, the nerve injury-induced Gal(2)
      upregulation in motor neurons suggests a role for galanin in
      survival/regeneration mechanisms.

PMID- 16626648
TI  - Studying inner ear protein-protein interactions using FRET and FLIM.
AB  - Molecular genetic studies of the inner ear have recently revealed a large number
      of previously undescribed proteins, but their functions remain unclear. Optical
      methods such as FRET and FLIM are just beginning to be applied to the study of
      functional interactions between novel inner ear proteins. This review discusses
      the various methods for employing FRET and FLIM in protein-protein interaction
      studies, their advantages and pitfalls, with examples drawn from inner ear
      studies.

PMID- 16626649
TI  - The coding sequence of amyloid-beta precursor protein APP contains a neural
      specific promoter element.
AB  - The amyloid-beta precursor protein APP is generally accepted to be involved in
      the pathology of Alzheimer's disease. Since its physiological role is still
      unclear, we decided to study the function of APP via stable transgenesis in the
      amphibian Xenopus laevis. However, the application of constructs encoding
      (mutant) APP fused to the C-terminus of the green fluorescent protein GFP (GFP
      APP), and harboring a tissue-specific or an inducible gene promoter did not
      result in transgene expression of APP in neuronal and neuroendocrine cells.
      Surprisingly, a construct encoding either Xenopus or human APP fused to the N
      terminus of GFP (APP-GFP) gave fluorescence throughout the whole brain of the
      tadpole, despite the fact that a proopiomelanocortin gene promoter was used to
      target transgene expression specifically to the intermediate pituitary cells.
      Detailed analysis with deletion mutants revealed the presence of a neural
      specific, transcriptionally active DNA element within the 3'-end of the APP
      coding sequence that gave rise to an aberrant transcript and protein in the APP
      GFP transgenic animals. The DNA element appears to prevent proper APP transgene
      expression in Xenopus neuronal and neuroendocrine cells. Thus, the coding
      sequences of Xenopus and human APP contain a neural-specific promoter element,
      the physiological significance of which is at present unclear.

PMID- 16626650
TI  - Prenatal cocaine exposure accelerates morphological changes and transient
      expression of tyrosine hydroxylase in the cochlea of developing rats.
AB  - Prenatal cocaine exposure causes alterations in auditory brainstem response in
      children and experimental animals and has adverse effects on auditory information
      processing and language skills in children. These effects may result from lesions
      in the cochlea since this organ is particularly sensitive to chemical insults
      during the development. We have thus studied here the effect of prenatal cocaine
      exposure on the maturation of the rat cochlea using the transient non
      catecholaminergic expression of tyrosine hydroxylase in spiral ganglion neurons
      as an index of cochlear maturation and morphometry to evaluate the maturation of
      primary auditory neurons and the organ of Corti. We showed that prenatal cocaine
      exposure accelerated the cochlear maturation. In the basal coil of cochleas from
      PND8 cocaine-treated pups, the Kolliker's organ had disappeared, the tunnel of
      Corti was opened, and the stria vascularis no longer contained undifferentiated
      marginal cells. The maximum expression of tyrosine hydroxylase in type I primary
      auditory neurons occurred at PND8 instead of PND12 in pair-fed controls. On the
      other hand, the prenatal cocaine exposure had no effect on the width and height
      of the organ of Corti, spiral ganglion volume and number and size of primary
      auditory neurons. In conclusion, our data suggest that prenatal cocaine exposure,
      though not lethal to primary auditory neurons, accelerates aspects of the
      cochlear sensorineural maturation. This accelerated cochlear maturation in
      cocaine-treated rat pups could cause auditory dysfunctions by desynchronizing the
      development of the whole auditory pathway.

PMID- 16626651
TI  - Loss of nicastrin elicits an apoptotic phenotype in mouse embryos.
AB  - Nicastrin is a member of the high molecular weight presenilin complex that plays
      a central role in gamma-secretase cleavage of numerous type-1 membrane-associated
      proteins required for cell signaling, proliferation and lineage development. We
      have generated a nicastrin-null mouse line by disruption of exon 3. Similar to
      previously described nicastrin-null mice, these animals demonstrate severe growth
      retardation, mortality beginning at embryonic age 10.5 days, and marked
      developmental abnormalities indicative of a severe Notch phenotype. Preceding
      their mortality, 10.5-day-old nicastrin-null embryos were found to also exhibit
      specific apoptosis within regions showing profound deformities, particularly in
      the developing heart and brain. This result suggests that complete disruption of
      presenilin complexes elicits programmed cell death, in addition to a Notch
      phenotype, which may contribute to the developmental abnormalities and embryonic
      mortality of nicastrin-null mice and possibly neurodegeneration in Alzheimer's
      disease.

PMID- 16626652
TI  - Interaction of adenosine and naloxone on regional cerebral blood flow in morphine
      dependent rats.
AB  - The present research aimed at investigating the opioid-adenosine interaction on
      regional cerebral blood flow (rCBF). Therefore rCBF in the sensory cortex of
      morphine-naive and -dependent rats was measured using the laser-Doppler flowmetry
      technique. The results showed that adenosine (10(-5), 10(-4), 10(-3) M)
      significantly increased rCBF in morphine-dependent rats (MDR) (P < 0.01). This
      effect was inhibited by theophylline (5 x 10(-5) M). Also systemic naloxone (0.5,
      1.5 and 3 mg/kg, s.c.) significantly increased rCBF in MDR and it was accompanied
      by elevated blood pressure and heart rate. Local adenosine (10(-4) M)
      significantly augmented naloxone (0.5 mg/kg)-induced increase in rCBF of MDR but
      had no significant effect on naloxone's (1.5 and 3 mg/kg) increasing effect on
      rCBF. Theophylline also has no effect on naloxone increasing effect on rCBF.
      These data suggest that adenosine receptors responsiveness increase in sensory
      cortex of MDR. Naloxone also highly increased rCBF of MDR that probably not
      interfere with adenosine receptors. Also, it seems that adenosine acts as a
      modulator in rCBF regulation of morphine-dependent and morphine withdrawal rats.

PMID- 16626653
TI  - Using advance information in dynamic cognitive control: an ERP study of task
      switching.
AB  - Ensuring that behavior remains appropriate over time requires dynamic, flexible
      control. We used the task-switching procedure to investigate the mechanisms
      whereby advance information is used to control behavior under conditions of
      frequently changing task-rules. The color of target stimuli signaled which task
      set (or behavioral 'rule') was required on each trial. We provided different
      forms of advance information in two conditions and found a double dissociation in
      their effects: visual precues ('precueing') facilitated task-switching, whereas a
      fixed task-sequence ('predictability') facilitated task-repetition. In addition,
      precueing was associated with a late parietal positive ERP which preceded target
      onset, whereas predictability produced an increase in the target-locked centro
      parietal P3b ERP. We suggest that these results indicate the activity of two
      distinct mechanisms. The first, driven by a task-cue and indexed by the late
      parietal positivity, may drive efficient task-performance on precued switch
      trials but occurs too late on non-precued switch trials to index an anticipatory
      task-set reconfiguration process. The second may constitute active consolidation
      or maintenance of a particular task-set which occurs at least one trial ahead,
      when task-repetitions are predictable, and results in facilitation of target
      stimulus evaluation.

PMID- 16626654
TI  - Hair cell development: commitment through differentiation.
AB  - The perceptions of sound, balance and acceleration are mediated through the
      vibration of stereociliary bundles located on the lumenal surfaces of
      mechanosensory hair cells located within the inner ear. In mammals, virtually all
      hair cells are generated during a relatively brief period in embryogenesis with
      any subsequent hair cell loss leading to a progressive and permanent loss of
      sensitivity. In light of the importance of these cells, considerable effort has
      been focused on understanding the molecular genetic pathways that regulate their
      development. The results of these studies have begun to elucidate the signaling
      molecules that regulate several key events in hair cell development. In
      particular, significant progress has been made in the understanding of hair cell
      commitment, survival and differentiation. In addition, several aspects of the
      development of the stereociliary bundle, including its elongation and
      orientation, have recently been examined. This review will summarize results from
      each of these developmental events and describe the molecular signaling pathways
      involved.

PMID- 16626655
TI  - Cannabinoid system in the budgerigar brain.
AB  - Cannabinoid receptor density and cannabinoid receptor-mediated G protein
      stimulation were studied by autoradiographic techniques throughout the budgerigar
      (Melopsittacus undulatus) brain. The maximal CB(1) receptor density value (using
      [(3)H]CP55,940 as radioligand) was found in the molecular layer of the cerebellum
      (Mol), and high binding values were observed in the nucleus taeniae amygdalae
      (TnA), nucleus preopticus medialis, and nucleus pretectalis. The highest net
      stimulated [(35)S]GTPgammaS binding values induced by the selective CB(1)
      receptor agonist WIN55,212-2 were observed in the nucleus paramedianus internus
      thalami, and high values of [(35)S]GTPgammaS binding were observed in the TnA,
      Mol, arcopallium dorsale and arcopallium intermedium. The distribution data
      suggest that in the budgerigar, as previously indicated in mammals, cannabinoid
      receptors may be related to the control of several brain functions in the motor
      system, memory, visual system, and reproductive behavior. The discrepancies
      between the cannabinoid receptor densities and the cannabinoid receptor-mediated
      stimulation found in several budgerigar brain nuclei support the hypothesis,
      previously described for mammals, of the existence of different G(i/o) protein
      populations able to associate with the cannabinoid receptors, depending on the
      brain structure, and could reflect the relative importance that cannabinoid
      transmission could exerts in each cerebral area.

PMID- 16626656
TI  - AV3V lesions reduce the pressor response to L-glutamate into the RVLM.
AB  - Neurons from the rostral ventrolateral medulla (RVLM) directly activate
      sympathetic pre-ganglionic neurons in the spinal cord. Hypertensive responses and
      sympathetic activation produced by different stimuli are strongly affected by
      lesions of the preoptic periventricular tissue surrounding the anteroventral
      third ventricle (AV3V region). Therefore, in the present study, we investigated
      the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the
      AV3V region on the pressor responses produced by injections of the excitatory
      amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats
      with sham or electrolytic AV3V lesions and a stainless steel cannula implanted
      into the RVLM were used. The pressor responses produced by injections of L
      glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39
      +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6,
      39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2
      and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in
      sham or AV3V-lesioned rats produced no significant change in the heart rate (HR).
      Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium
      nitroprusside, respectively, and the pressor and bradycardic responses to
      chemoreflex activation with iv potassium cyanide were not modified by AV3V
      lesions. The results suggest that signals from the AV3V region are important for
      sympathetic activation induced by L-glutamate into the RVLM.

PMID- 16626657
TI  - Effects of the abused inhalant toluene on ethanol-sensitive potassium channels
      expressed in oocytes.
AB  - Toluene (methylbenzene) is representative of a class of industrial solvents that
      are voluntarily inhaled as drugs of abuse. Previous data from this laboratory and
      others have shown that these compounds alter the function of a variety of ion
      channels including ligand-gated channels activated by ATP, acetylcholine, GABA,
      glutamate and serotonin, as well as voltage-dependent sodium and calcium
      channels. It is less clear what effects toluene may have on potassium channels
      that act to reduce the excitability of most cells. Previous studies have shown
      that ethanol potentiates the function of both the large conductance, calcium
      activated potassium channel (BK) and specific members of the G-protein-coupled
      inwardly rectifying potassium channels (GirKs). Since toluene and other abused
      inhalants share many behavioral effects with ethanol, it was hypothesized that
      toluene would also enhance the function of these channels. This hypothesis was
      tested using two-electrode voltage-clamp electrophysiology to measure the
      activity of BK and GirK potassium channel currents expressed in Xenopus laevis
      oocytes. As reported previously, ethanol potentiated currents in oocytes
      expressing either BK or GirK2 channels. In contrast, toluene caused a
      concentration-dependent inhibition of BK channel currents with 3 mM producing
      approximately 50% inhibition of control currents. Currents in oocytes injected
      with GirK2 mRNA were also inhibited by toluene while those expressing GirK1/2 and
      1/4 channels were minimally affected. In oocytes co-injected with mRNA for GirK2
      and the mGluR1a metabotropic receptor, exposure to glutamate potentiated currents
      evoked by a high-potassium solution. Toluene inhibited these glutamate-activated
      currents to approximately the same degree as those induced under basal
      conditions. The results of these studies show that toluene has effects on BK and
      GirK channels that are opposite to those of ethanol, suggesting that these
      channels are unlikely to underlie behaviors that these two drugs of abuse share.

PMID- 16626658
TI  - Protective role of heat shock and heat shock protein 70 in lactacystin-induced
      cell death both in the rat substantia nigra and PC12 cells.
AB  - Proteasomal dysfunction plays an important role in the pathogenesis of Parkinson
      disease (PD). Although clinical and experimental evidence continues to accumulate
      indicating heat shock protein 70 (HSP70) is significant in the pathogenesis of
      PD, few studies have been made to investigate the role of HSP70 under the
      condition of proteasome dysfunction. In in vivo study, we infused lactacystin
      into the unilateral substantia nigra (SN) of Sprague-Dawley rats with or without
      preceding whole body hyperthermia (WBH). Immunohistochemical studies showed the
      death of dopaminergic neurons and activated microglia in the SN. Lactacystin with
      prior WBH increased the expression of HSP70 more than did lactacystin alone and
      decreased lactacystin-induced dopaminergic neuronal death in the SN. In PC12
      cells, heat shock pretreatment decreased lactacystin-induced cell death. Although
      additional treatment of nocodazole, ammonium chloride, and 3-methyladenine
      augmented cell death by lactacystin, heat shock pretreated to these drugs offsets
      their additional toxicity. These results indicate that heat shock proteins,
      especially HSP70, could play an important role under the condition of proteasome
      dysfunction in part by fostering aggresome formation and lysosome-mediated
      autophagy.

PMID- 16626659
TI  - Kainate receptor activation potentiates GABAergic synaptic transmission in the
      nucleus accumbens core.
AB  - Inhibitory synaptic transmission plays an important role in regulating the
      activity of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc). The
      kainate (KA) subtype of ionotropic glutamate receptor has been shown to potently
      modulate GABAergic synaptic transmission in several brain regions. Although KA
      receptor subunits are expressed in the NAcc, KA receptor modulation of GABAergic
      synaptic transmission in this brain region has not been previously examined. In
      the current study, we sought to determine if KA receptor activation could alter
      inhibitory synaptic transmission in the NAcc as it has been shown to do in other
      brain regions. Using the whole cell patch-clamp technique, we demonstrate that KA
      receptor activation potentiates evoked GABAergic synaptic transmission and
      increases the frequency of spontaneous, but not miniature, GABA(A)-receptor
      mediated IPSCs in the NAcc. In contrast, KA has no effect on currents evoked by
      exogenous application of GABA onto MSNs. Taken together, these data suggest that
      activation of KA receptors in the NAcc core potently facilitates action-potential
      dependent GABAergic synaptic transmission, likely via an excitation of
      presynaptic GABAergic interneurons.

PMID- 16626660
TI  - Regeneration of descending projections in Xenopus laevis tadpole spinal cord
      demonstrated by retrograde double labeling.
AB  - Xenopus laevis tadpoles functionally recover from spinal cord transection.
      Because this recovery requires the tadpole to metamorphose, it may result from
      compensatory changes initiated by de novo growth of axons involved in limb
      dominant locomotion rather than from regeneration of cut axons. To determine
      whether axonal regrowth contributes to functional recovery, sequential retrograde
      double labeling with two fluorescent dextran amines was used to identify neurons
      with regenerated axons. Rhodamine dextran amine was applied to hemisected spinal
      cords of prometamorphic tadpoles between the 4th and 5th vertebrae. After
      metamorphosis, in animals that had recovered movement, fluorescein dextran amine
      was applied to the lumbar spinal cord. Two weeks later, the CNS of these animals
      was examined for the presence of double-labeled neurons, i.e., those whose axons
      had regenerated. Double-labeled neurons were found in the reticular, raphe, and
      solitary tract nuclei, and in the interstitial nucleus of the medial longitudinal
      fasciculus. Because Xenopus expresses all the known mammalian molecular
      inhibitors of CNS axon regeneration, the determination that these
      phylogenetically conserved populations of neurons are indeed capable of axon
      regeneration should facilitate molecular studies of successful recovery from
      spinal cord trauma.

PMID- 16626661
TI  - Expression profiling of genes encoding glutamate and GABA receptor subunits in
      three immortalized GnRH cell lines.
AB  - Gonadotropin-releasing hormone (GnRH) plays a central role in regulating
      development and function of the reproductive axis, and its secretion is known to
      be influenced by glutamate and GABA. In the present study, we used gene
      microarrays and RT-PCR to compare the expression profiles of glutamate and GABA
      receptor subunits in three immortalized GnRH cell lines: GT1-1, GT1-7, and Gn10.
      All of these cell lines expressed the AMPA glutamate receptor subunit genes GluR2
      and GluR4, but only the GT1-1 and GT1-7 cells expressed the kainate glutamate
      receptor subunit gene KA2. Additionally, GluRdelta2, a subunit that can form
      heteromeric receptors with kainate and AMPA subunits, was present in GT1-1 and
      Gn10 cells but not in GT1-7 cells. Genes encoding the GABA(A) receptor alpha3,
      beta2, beta3, epsilon, and pi subunits, as well as the GABA(B) receptor 1
      subunit, were evident in all three cell lines. However, the gene encoding the
      expression of GABA(A) receptor gamma subunit was noticeably absent. Taken
      together, these data demonstrate comprehensive screening of neurotransmitter
      receptor genes in a controlled neuronal culture system, and reveal novel
      features.

PMID- 16626662
TI  - Temperature: an important experimental variable in studying PKC modulation of
      ligand-gated ion channels.
AB  - Amphibian oocyte and mammalian heterologous expression systems are often used to
      investigate the function of recombinant ion channels using electrophysiological
      techniques. Although both systems have yielded important information, the results
      obtained in these systems are sometimes conflicting. Oocytes and mammalian cells
      differ in their physiological temperature requirements. While room temperature is
      within the physiological temperature range for oocytes, this temperature is far
      below that required by mammalian cells. Since electrophysiological studies are
      often performed in both oocytes and mammalian cells at room temperature, we
      sought to determine if recording temperature could be a factor in some disparate
      results obtained in these cell types. For these studies, we examined phorbol
      ester modulation of GABA(A) and glycine receptors. Consistent with the
      literature, at room temperature, PMA (phorbol 12-myristate 13-acetate) produced a
      large reproducible decrease in the peak amplitude of GABA and glycine-gated
      currents in Xenopus oocytes. In contrast, PMA was ineffective in modulating these
      heterologously expressed receptors at room temperature in human embryonic kidney
      (HEK) 293 cells. However, when electrophysiological experiments were performed at
      35 degrees C in HEK 293 cells, PMA decreased the function of these receptors. Our
      results indicate that the temperature at which electrophysiological studies are
      conducted is an important experimental variable. To determine the extent to which
      electrophysiological recordings are performed at physiological temperatures in
      HEK 293 cells, a PubMed search was conducted using the search terms "patch clamp"
      and "HEK" for the years 2003-2004. This search revealed that only 15% of the
      patch clamp studies were reported to have been conducted in the temperature range
      of 32-37 degrees C. The results of our study indicate that temperature is an
      important experimental variable that requires rational consideration in the
      design of electrophysiological experiments.

PMID- 16626663
TI  - Alternation of galanin in nociceptive modulation in the central nervous system of
      rats during morphine tolerance: a behavioral and immunohistochemical study.
AB  - The present study was performed to investigate the alternation of galanin in
      nociceptive modulation and galanin-like immunoreactivity in the central nervous
      system of rats after morphine tolerance. The hindpaw withdrawal latencies to both
      thermal and mechanical stimulation increased significantly after
      intracerebroventricular injection of 3 nmol of galanin in opioid-naive rats. The
      antinociceptive effect induced by galanin was attenuated remarkably at the same
      dose in morphine-tolerant rats. Furthermore, an up-regulation of galanin-like
      immunoreactivity in the arcuate nucleus of hypothalamus of morphine-tolerant rat
      was observed by immunohistochemical methods, whereas no significant changes were
      detected in periaqueductal gray. The present study demonstrated that there are
      alternations in both galanin-induced antinociception and galanin-like
      immunoreactivity in the brain of rat after morphine tolerance. The results
      suggest an involvement of galanin in the central nervous system in morphine
      tolerance.

PMID- 16626664
TI  - Developmental pattern of expression of BMP receptors and Smads and activation of
      Smad1 and Smad5 by BMP9 in mouse basal forebrain.
AB  - Basal forebrain cholinergic neurons play critical roles in the organization of
      brain cortical structures and in processes such as learning and memory. We have
      previously shown that bone morphogenetic protein (BMP) 9, a member of the
      transforming growth factor (TGF) beta superfamily of cytokines, is a
      differentiating factor for cholinergic central nervous system neurons. However,
      whereas the basic signal transduction pathways for most known members of the TGF
      beta superfamily have been well characterized in brain and other organs, nothing
      is known about the signal transduction pathway of BMP9 in the brain. Here, we
      describe the pattern of expression of BMP receptors, including Bmpr-Ia, Bmpr-Ib,
      Bmpr-II, Actr-I. Actr-Ib, Actr-II and Actr-IIb, Alk-1, and Smad proteins (Smads 1
      5 and Smad8) in the septal region of the basal forebrain during mouse
      development. Using cultured basal forebrain cells derived from embryonic day (E)
      14 mice, we show that BMP9 causes phosphorylation of Smad1 and Smad5, formation
      of a complex of Smad4 with Samd1 and/or Smad5, and translocation of these
      proteins into the nucleus. These data show that BMP9 activates the canonical BMP
      signaling pathway and suggest that this could be one of the mechanisms
      responsible for the induction of the cholinergic phenotype by BMP9 in the basal
      forebrain.

PMID- 16626665
TI  - The mPer1 clock gene expression in the rd mouse suprachiasmatic nucleus is
      affected by the retinal degeneration.
AB  - Endogenous rhythms of mammals are controlled by the clock located in the
      suprachiasmatic nucleus (SCN). The molecular mechanism of a clock involves
      transcription/translation-based feedback loops in which the expression of the so
      called "clock genes" is suppressed periodically by their protein products.
      Previous studies reported influence of the eye itself on the circadian
      oscillation of the SCN, apart from the well-known photic readjustment of the
      central clock. With this in mind, we decided to analyze the mPer1 clock gene
      expression in the retinally degenerate (rd) mouse SCN by means of
      immunohistochemical techniques. Our objective was to detect possible alterations
      of the daily endogenous oscillation of PER1 protein in the SCN of these rd mice,
      as well as to make clear whether or not this protein was involved in the
      resetting of the central clock in a manner similar to wild-type animals. We found
      that the endogenous levels of PER1 protein were reduced in the SCN of rd mice
      throughout the 24-h cycle, which suggests that loss of classic photoreceptors
      influences somehow the main mechanism of the SCN clock. Light stimulation induced
      a parallel increase of Per1 expression at the subjective night, but not at the
      subjective day, in both rd and wild-type mice. Therefore, SCN readjustment by
      light in the rd mice occurs with a pattern similar to wild-type controls, despite
      the reduced PER1 protein levels detected. The effect of retinal degeneration on
      the circadian system and the possible interactions between the retinal and the
      SCN clocks are discussed.

PMID- 16626666
TI  - Memantine, an uncompetitive low affinity NMDA open-channel antagonist improves
      clinical rating scores in a multiple infarct embolic stroke model in rabbits.
AB  - The blockade of NMDA receptors has been pursued as a strategy to reduce the
      consequences of acute ischemic stroke (AIS) and NMDA receptors remain a valid
      therapeutic target to treat AIS. Because the pharmacological and toxicity profile
      of memantine in Alzheimer's disease patients appears to be good, we determined
      whether memantine would be effective at improving behavioral performance
      following embolic strokes in rabbits. For these studies, we used a rabbit
      multiple infarct ischemia model with a well-defined behavioral endpoint. In this
      study, memantine dissolved in PBS was given intravenously either as a bolus
      injection (over 1 min) or infused over 60 min. The P(50) of the control groups
      measured 24 h after embolization were 1.12 +/- 0.18 mg and 1.08 +/- 0.23 mg for
      the bolus injected and infused groups, respectively. Bolus injections of
      memantine at 1 mg/kg and 10 mg/kg were not effective at altering the P(50) value
      and memantine at a dose of 25 mg/kg was lethal. However, slowly infused memantine
      (25 mg/kg) significantly increased the P(50) value to 2.31 +/- 0.48 mg and 3.13
      +/- 1.13 mg when given 5 and 60 min following embolization, respectively.
      Memantine administered 180 min following embolization also increased the P(50)
      value to 2.69 +/- 2.21 mg, but the response was variable. These results suggest
      that uncompetitive NMDA antagonists, more specifically open channel blockers,
      which may be alternatives to high affinity NMDA antagonists, may have substantial
      therapeutic benefit for the treatment of AIS and memantine or new dual activity
      analogs of memantine should be further pursued as a useful therapy to treat the
      behavioral deficits associated with multiple-infarct ischemia.

PMID- 16626667
TI  - Genetic association between Ubiquitin Carboxy-terminal Hydrolase-L1 gene S18Y
      polymorphism and sporadic Alzheimer's disease in a Chinese Han population.
AB  - Increasing evidence indicates that the dysfunction of ubiquitin-proteasome system
      (UPS) is associated with Alzheimer's disease (AD). In the ubiquitin-proteasome
      pathway, Ubiquitin Carboxy-terminal Hydrolase-L1 (UCH-L1) plays an important role
      for the cellular clearance of abnormal proteins. Since a substitution of serine
      by tyrosine at codon 18, exon 3 (S18Y polymorphism) of the UCH-L1 gene exhibits a
      protective effect against the development of degenerative disease such as
      sporadic Parkinson's disease (PD) in several different ethnic groups, we
      hypothesized that UCH-L1 gene S18Y polymorphism may have that same effect on the
      pathologic process of AD. We examined UCH-L1 S18Y polymorphism genotypes of 116
      sporadic AD patients and 123 healthy subjects in Chinese Han population using PCR
      restriction fragment length polymorphism (RFLP) analysis. The allele and genotype
      data as well as data after stratification by age of onset failed to demonstrate
      any association between AD and S18Y polymorphism. However, after stratification
      by gender, female AD patients showed significantly less frequencies of Y allele
      and YY genotype in S18Y polymorphism than female controls (P = 0.003 and P =
      0.015 respectively). We conclude that Y allele and YY genotype of S18Y in the UCH
      L1 gene may have a protective effect against sporadic AD in female subjects,
      probably due to altering the function of UCH-L1 and the interactions among
      different risk factors.

PMID- 16626668
TI  - Effects of continuous masking noise on tone-evoked magnetic fields in humans.
AB  - Two different types of steep loudness growth have been reported in detail in
      psychoacoustical studies but have rarely been evaluated by objective methods in
      humans. One occurs in inner-ear hearing-impaired patients and is known as
      loudness recruitment. Another similar phenomenon is observed in healthy subjects
      with concurrent presence of background noise. Concerning the first type, our
      previous study using magnetoencephalography (MEG) showed that enhancement of the
      dipole moment of N100m with increase in stimulus intensity was greater in
      patients than in normal individuals. However, it is unclear whether the
      enhancement of activity in auditory cortex will also be detected with background
      noise in healthy subjects. To elucidate the effects of continuous background
      noise on tone-evoked cortical activity, we measured auditory-evoked magnetic
      fields (AEFs) from 7 normal-hearing subjects in two different conditions, with
      and without 55 dB SPL continuous masking white noise (noise/quiet conditions).
      The stimuli were 200 ms 1-kHz tones delivered monaurally and randomly at 4
      different intensities (40-70 dB SPL) with constant 1-s interstimulus intervals.
      The N100m increased in amplitude and decreased in latency as a function of
      stimulus intensity in both noise and quiet conditions. The dipole moment of N100m
      was significantly smaller in the noise than in the quiet condition, showing that
      continuous background noise suppresses the strength of tone-evoked cortical
      responses. The mechanisms underlying these two psychoacoustically similar
      phenomena of rapid loudness growth thus differ.

PMID- 16626669
TI  - DNA microarray analysis of striatal gene expression in symptomatic transgenic
      Huntington's mice (R6/2) reveals neuroinflammation and insulin associations.
AB  - Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder
      caused by CAG repeat expansion in the gene that codes for the protein huntingtin.
      The underlying neuropathological events leading to the selectivity of striatal
      neuronal loss are unknown. However, the huntingtin mutation interferes at several
      levels of normal cell function. The complexity of this disease makes microarray
      analysis an appealing technique to begin the identification of common pathways
      that may contribute to the pathology. In this study, striatal tissue was
      extracted for gene expression profiling from wild-type and symptomatic transgenic
      Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We
      interrogated a 15 K high-density mouse EST array not previously used for HD and
      identified 170 significantly differentially expressed ESTs in symptomatic R6/2
      mice. Of the 80 genes with known function, 9 genes had previously been identified
      as altered in HD. 71 known genes were associated with HD for the first time. The
      data obtained from this study confirm and extend previous observations using DNA
      microarray techniques on genetic models for HD, revealing novel changes in
      expression in a number of genes not previously associated with HD. Further
      bioinformatic analysis, using software to construct biological association maps,
      focused attention on proteins such as insulin and TH1-mediated cytokines,
      suggesting that they may be important regulators of affected genes. These results
      may provide insight into the regulation and interaction of genes that contribute
      to adaptive and pathological processes involved in HD.

PMID- 16626670
TI  - Hydroxylation of D-phenylalanine as a novel approach to detect hydroxyl radicals:
      application to cardiac pathophysiology.
AB  - OBJECTIVE: Research in the pathophysiology of ischemia/reperfusion or redox
      signaling is hindered by lack of simple methodology to measure short-lived oxygen
      radicals. In the presence of hydroxyl radical ((*)OH), d-phenylalanine (d-Phe)
      yields para-, meta- and ortho-tyrosine. We have previously demonstrated that d
      Phe can accurately detect (*)OH formation in chemical, enzymatic and cellular
      systems by simple HPLC methodology [Anal Biochem 290:138;2001]. In the present
      study, we tested whether d-Phe hydroxylation can be used to detect (*)OH
      formation in intact organs. METHODS: Rat hearts were perfused with buffer
      containing 5 mM d-Phe and subjected to 30 min of total global ischemia at 37
      degrees C followed by 45 min of reperfusion. Quantitative analysis of the three
      hydroxytyrosine isomers was achieved by HPLC-based electrochemical detection of
      cardiac venous effluent, with the analytical cells operating in the oxidative
      mode. The detection limit of this assay was <10 fmol. RESULTS: Under baseline
      conditions, hydroxytyrosine release from the heart was very low ( congruent
      with0.8 nmol/min/g). However, a prominent tyrosine burst occurred immediately
      upon post-ischemic reflow. In cardiac effluent collected 40 s into reperfusion,
      the hydroxytyrosine concentration was more than 40 times greater than at
      baseline; hydroxytyrosine concentration then progressively declined, to return to
      pre-ischemic values by 5 min of reperfusion. In parallel experiments, formation
      of hydroxytyrosines was markedly reduced in hearts reperfused in the presence of
      the (*)OH scavenger mannitol. Inclusion of 5 mm d-Phe in the perfusion medium
      altered neither basal cardiac function nor coronary vascular tone, but it
      enhanced recovery of myocardial function during post-ischemic reperfusion,
      consistent with direct reaction with (*)OH. CONCLUSION: Our results demonstrate
      that d-Phe is a sensitive method for detection of (*)OH generation in the heart.
      Since d-Phe is not a substrate for endogenous enzymes, it can be exploited as a
      reliable method to measure (*)OH formation under a variety of pathophysiological
      conditions.

PMID- 16626671
TI  - I(Kr) contributes to the altered ventricular repolarization that determines long
      term cardiac memory.
AB  - OBJECTIVE: Cardiac memory (CM) is characterized by an altered T-wave morphology,
      which reflects altered repolarization gradients. We hypothesized that the delayed
      rectifier currents, I(Kr) and I(Ks), might contribute to these repolarization
      changes. METHODS: We studied conscious, chronically instrumented dogs paced from
      the postero-lateral left ventricular (LV) wall at rates 5-10% faster than sinus
      rate for 3 weeks. ECGs during sinus rhythm were recorded on days 0, 7, 14 and 21
      of pacing. Within 3 weeks, CM achieved steady state, hearts were excised, and
      epicardial and endocardial tissues and myocytes were studied. RESULTS: In unpaced
      controls, action potential duration to 50% and 90% repolarization (APD) in
      epicardium was shorter than in endocardium (P < 0.05); in CM epicardial APD
      increased at CL > or = 500 ms, while endocardial APD was either unchanged or
      decreased such that the transmural gradient seen in controls diminished (P <
      0.05). A transmural I(Kr) gradient occurred in controls (epicardium>endocardium,
      P < 0.05) and was reversed in CM. No I(Ks) transmural gradient was found in
      controls, while in CM endocardial I(Ks) was greater than epicardial at greater
      than +50 mV. Canine ERG (cERG) mRNA and protein in epicardium > endocardium in
      controls (P < 0.05), and this difference was lost in CM. Expression levels of
      KCNQ1 and KCNE1 protein were similar in all groups. CONCLUSIONS: A
      transcriptionally induced change in epicardial I(Kr) contributes to the altered
      ventricular repolarization that characterizes CM.

PMID- 16626672
TI  - Effects of adenosine deaminase and A1 receptor deficiency in normoxic and
      ischaemic mouse hearts.
AB  - OBJECTIVE: Adenosine deaminase (ADA) may be multifunctional, regulating adenosine
      levels and adenosine receptor (AR) agonism, and potentially modifying AR
      functionality. Herein we assess effects of ADA (and A1AR) deficiency on AR
      mediated responses and ischaemic tolerance. METHODS: Normoxic function and
      responses to 20 or 25 min ischaemia and 45 min reperfusion were studied in
      isolated hearts from wild-type mice and from mice deficient in ADA and/or A1ARs.
      RESULTS: Neither ADA or A1AR deficiency significantly modified basal
      contractility, although ADA deficiency reduced resting heart rate (an effect
      abrogated by A1AR deficiency). Bradycardia and vasodilation in response to AR
      agonism (2-chloroadenosine) were unaltered by ADA deficiency, while A1AR
      deficiency eliminated the heart rate response. Adenosine efflux increased 10- to
      20-fold with ADA deficiency (at the expense of inosine). Deletion of ADA improved
      outcome from 25 min ischaemia, reducing ventricular diastolic pressure (by 45%;
      21+/-4 vs. 38+/-3mm Hg) and lactate dehydrogenase (LDH) efflux (by 40%; 0.12+/
      0.01 vs. 0.21+/-0.02 U/g/min ischaemia), and enhancing pressure development (by
      35%; 89+/-6 vs. 66+/-5mm Hg). Similar protection was evident after 20 min
      ischaemia, and was mimicked by the ADA inhibitor EHNA (5 microM). Deletion of ADA
      also enhanced tolerance in A1AR deficient hearts, though effects on diastolic
      pressure were eliminated. CONCLUSIONS: Deficiency of ADA does not alter
      sensitivities of cardiovascular A1 or A2ARs (despite markedly elevated
      [adenosine]), but significantly improves ischaemic tolerance. Conversely, A1AR
      deficiency impairs ischaemic tolerance. Effects of ADA deficiency on diastolic
      pressure appear solely A1AR-dependent while other ARs or processes additionally
      contribute to improved contractile recovery and reduced cell death.

PMID- 16626673
TI  - alpha-Tocopherol protects against alpha-naphthylisothiocyanate-induced
      hepatotoxicity in rats less effectively than melatonin.
AB  - The protective effect of alpha-tocopherol (alpha-Toc), which exerts antioxidant
      and anti-inflammatory actions, against alpha-naphthylisothiocyanate (ANIT)
      induced hepatotoxicity in rats was compared with that of melatonin because orally
      administered melatonin is known to protect against ANIT-induced hepatotoxicity in
      rats through its antioxidant and anti-inflammatory actions. Rats intoxicated once
      with ANIT (75 mg/kg, intraperitoneal (i.p.)) showed liver cell damage and biliary
      cell damage with cholestasis at 24 h, but not 12 h, after intoxication. ANIT
      intoxicated rats received alpha-Toc (100 or 250 mg/kg) or melatonin (100 mg/kg)
      orally at 12 h after intoxication. The alpha-Toc administration protected against
      liver cell damage in ANIT-intoxicated rats, while the melatonin administration
      protected against both liver cell damage and biliary cell damage with
      cholestasis. ANIT-intoxicated rats had increased hepatic lipid peroxide
      concentration and myeloperoxidase activity at 12 and 24 h after intoxication.
      ANIT-intoxicated rats also had increased serum alpha-Toc and non-esterified fatty
      acid (NEFA) concentrations at 12 and 24 h after intoxication and increased serum
      triglyceride and total cholesterol concentrations at 24h. The administration of
      alpha-Toc to ANIT-intoxicated rats increased the hepatic alpha-Toc concentration
      with further increase in the serum alpha-Toc concentration and attenuated the
      increased hepatic lipid peroxide concentration and myeloperoxidase activity and
      serum NEFA concentration at 24 h after intoxication. The melatonin administration
      did not affect the hepatic alpha-Toc concentration but attenuated the increased
      hepatic lipid peroxide concentration and myeloperoxidase activity and serum alpha
      Toc, NEFA, triglyceride, and total cholesterol concentrations at 24 h after ANIT
      intoxication. These results indicate that orally administered alpha-Toc protects
      against ANIT-induced hepatotoxicity in rats possibly through its antioxidant and
      anti-inflammatory actions less effectively than orally administered melatonin.

PMID- 16626674
TI  - The biochemical alterations following administration of Kalpaamruthaa and
      Semecarpus anacardium in mammary carcinoma.
AB  - BACKGROUND: Breast cancer is one of the most common cancers in women of developed
      and developing countries. Lipids, lipoproteins and lipid-metabolizing enzymes
      have been associated with the risk of breast cancer. Kalpaamruthaa (KA) is a
      modified Siddha preparation, which contains Semecarpus anacardium Linn. (SA),
      Emblica officinalis (EO) and honey. OBJECTIVE: The present study was embarked to
      study the variations in lipids, lipid-metabolizing enzymes and lipoproteins in
      cancerous animals and the effect of KA on the lipid metabolism. MATERIALS AND
      METHODS: Breast cancer was induced in rats by administrating 7,12
      dimethylbenz(a)anthracene orally (25 mg/kg body weight). After 90 days of
      induction, KA (300 mg/kg body weight) and SA (200 mg/kg body weight) were
      administered for 14 days, by gastric intubations. The levels of lipids and lipid
      metabolizing enzymes were analysed in control and experimental animals. RESULTS
      AND CONCLUSION: The increased levels of total cholesterol, free cholesterol,
      phospholipids, triglycerides and free fatty acids and decreased levels of ester
      cholesterol in plasma, liver and kidney found in cancer suffering animals were
      reverted back to near normal levels on treatment with KA and SA. In mammary
      carcinoma bearing animals, the activities of total lipase, cholesterol ester
      synthase, and cholesterol ester hydrolase were significantly (p < 0.05) increased
      whereas lipoprotein lipase and lecithin cholesterol-acyl transferase were
      decreased. The levels of very low-density lipoprotein (VLDL) and low-density
      lipoprotein (LDL) were increased and the level of high-density lipoprotein (HDL)
      was decreased. These alterations were recouped back upon treatment with KA as
      well as SA when compared to cancer animals. The effects of KA were found to be
      more effective than SA. No significant alterations were observed in herbal
      preparation control animals when compared to control animals.

PMID- 16626675
TI  - Relationship between platelet counts and cartilage erosion in 436 cases of
      rheumatoid arthritis.

PMID- 16626676
TI  - Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density
      lipoprotein oxidation.
AB  - BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is an
      important contributor to atherosclerosis. Also, oxidized LDL is suspected to
      cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous
      competitive nitric oxide synthase inhibitor, which is suggested to be an
      independent risk factor for atherosclerosis. This study was performed to evaluate
      how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex
      vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise
      healthy subjects. METHODS: Plasma ADMA was determined using high performance
      liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by
      the lag time and rate of copper-induced LDL oxidation. The nitric oxide
      production in plasma was estimated based on nitrate (NO(3)(-)) determination and
      plasma oxidized LDL was determined by a capture ELISA. RESULTS: Low ADMA was a
      significant determinant for high LDL oxidation rate and concentration of plasma
      ADMA was associated with nitrate levels. CONCLUSIONS: There may be an interplay
      between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize
      that plasma ADMA has a bivalent role: high ADMA may have a protective role in
      decelerating LDL fatty acid oxidation and also a risk factor for endothelial
      dysfunction by decreasing availability of nitric oxide.

PMID- 16626677
TI  - Preliminary studies of sperm cryopreservation in the mushroom coral, Fungia
      scutaria.
AB  - Coral species throughout the world are facing severe environmental pressures.
      Because of this, we began cryobiological studies on the sperm of the mushroom
      coral, Fungia scutaria. We determined that F. scutaria sperm had a mean length of
      56 microm and head diameter of 2.5 microm, and a mean spontaneous ice nucleation
      temperature of -37.2 +/- 1.7 degrees C. When the sperm were exposed to the
      cryoprotectant glycerol for 5 or 20 min (at 10% v/v), no fertilized larvae were
      produced. However, when sperm were exposed for 20 min to propylene glycol (10%
      v/v), fertilizations were produced at the same rate as untreated control eggs and
      sperm (P > 0.05), but slightly less for dimethyl sulfoxide (10% v/v) (P < 0.05).
      Regardless, dimethyl sulfoxide caused less osmotic damage to the sperm membrane
      than did propylene glycol. Therefore, we used the dimethyl sulfoxide (10% v/v) to
      develop cryopreservation protocols that yielded good post-thaw morphology and
      motility (>95%) for coral sperm.

PMID- 16626678
TI  - Rapid cold-hardening increases membrane fluidity and cold tolerance of insect
      cells.
AB  - The rapid cold-hardening (RCH) response not only confers dramatic protection
      against cold-shock (non-freezing) injury, but also "instantaneously" enhances
      organismal performance. Since cold-shock injury is associated with damage to the
      cell membrane, we investigated the relationship between RCH and changes in cold
      tolerance and membrane fluidity at the cellular level. None of the adult flies
      (Sarcophaga bullata) in the cold-shocked treatment group survived direct transfer
      to -8 degrees C for 2 h; in contrast, 64.5% of flies in the RCH group survived
      exposure to -8 degrees C. Differences between the treatment groups also were
      reflected at the cellular level; only 21.3% of fat body cells in the cold-shocked
      group survived compared to 68.5% in the RCH group. Using 31P solid-state NMR
      spectroscopy, we determined that membrane fluidity increased concurrently with
      rapid cold-hardening of fat body cells. This result suggests that membrane
      characteristics may be modified very rapidly to protect cells against cold-shock
      injury.

PMID- 16626679
TI  - Contribution of extracellular ice formation and the solution effects to the
      freezing injury of PC-3 cells suspended in NaCl solutions.
AB  - The mechanism of cell injury during slow freezing was examined using PC-3 human
      prostate adenocarcinoma cells suspended in NaCl solutions. The objective was to
      evaluate contribution of extracellular ice and the 'solution effects' to freezing
      injury separately. The solution effects that designate the influence of elevated
      concentration were evaluated from a pseudo-freezing experiment, where cells were
      subjected to the milieu that simulated a freeze-thaw process by changing the NaCl
      concentration and the temperature at the same time. The effect of extracellular
      ice formation on cell injury was then estimated from the difference in cell
      survival between the pseudo-freezing experiment and a corresponding freezing
      experiment. When cells were frozen to a relatively higher freezing temperature at
      -10 degrees C, about 30% of cells were damaged mostly due to extracellular ice
      formation, because the concentration increase without ice formation to 2.5-M
      NaCl, i.e., the equilibrium concentration at -10 degrees C, had no effect on cell
      survival. In contrast, in the case of the lower freezing temperature at -20
      degrees C, about 90% of cells were injured by both effects, particularly 60-80%
      by the solution effects among them. The present results suggested that the
      solution effects become more crucial to cell damage during slow freezing at lower
      temperatures, while the effect of ice is limited to some extent.

PMID- 16626680
TI  - EphB2 regulates axonal growth at the midline in the developing auditory
      brainstem.
AB  - Eph receptors play important roles in axon guidance at the midline. In the
      auditory system, growth of axons across the midline is an important determinant
      of auditory function. The avian cochlear nucleus, n. magnocellularis (NM), makes
      bilateral projections to its target, n. laminaris (NL). We examined the time
      course of NM axon growth toward the midline, the expression of Eph proteins at
      the midline during this growth, and the effects of Eph receptor misexpression on
      axonal growth across the midline. We found that NM axons reach the midline at E4.
      At this age, EphB receptors are expressed at the ventral floor plate. Expression
      extends dorsally to the ventricular zone beginning at E5. NM axons thus grow
      across the midline at a time when EphB receptor expression levels are low.
      Overexpression of EphB2 at E2 resulted in misrouted axons that deflected away
      from transfected midline cells. This effect was observed when midline cells were
      transfected but not when NM cells alone were transfected, suggesting that EphB2
      acts non-cell autonomously and through reverse signaling. These data suggest an
      inhibitory role for midline Eph receptors, in which low levels permit axon growth
      and subsequently high levels prohibit growth after axons have crossed the
      midline.

PMID- 16626681
TI  - Scube2 mediates Hedgehog signalling in the zebrafish embryo.
AB  - The Hedgehog family of secreted morphogens specifies the fate of a large number
      of different cell types within invertebrate and vertebrate embryos, including the
      muscle cell precursors of the embryonic myotome of zebrafish. Formation of
      Hedgehog-sensitive muscle fates is disrupted within homozygous zebrafish mutants
      of the "you"-type class, the majority of which disrupt components of the Hedgehog
      (HH) signal transduction pathway. We have undertaken a phenotypic and molecular
      characterisation of one of these mutants, you, which we show results from
      mutations within the zebrafish orthologue of the mammalian gene scube2. This gene
      encodes a member of the Scube family of proteins, which is characterised by
      several protein motifs including EGF and CUB domains. Epistatic and molecular
      analyses position Scube2 function upstream of Smoothened (Smoh), the signalling
      component of the HH receptor complex, suggesting that Scube2 may act during HH
      signal transduction prior to, or during, receipt of the HH signal at the plasma
      membrane. In support of this model we show that scube2 has homology to cubilin,
      which encodes an endocytic receptor involved in protein trafficking suggesting a
      possible mode of function for Scube2 during HH signal transduction.

PMID- 16626682
TI  - Genetic regulatory networks programming hematopoietic stem cells and erythroid
      lineage specification.
AB  - Erythroid cell production results from passage through cellular hierarchies
      dependent on differential gene expression under the control of transcription
      factors responsive to changing niches. We have constructed Genetic Regulatory
      Networks (GRNs) describing this process, based predominantly on mouse data.
      Regulatory network motifs identified in E. coli and yeast GRNs are found in
      combination in these GRNs. Feed-forward motifs with autoregulation generate
      forward momentum and also control its rate, which is at its lowest in
      hematopoietic stem cells (HSCs). The simultaneous requirement for multiple
      regulators in multi-input motifs (MIMs) provides tight control over expression of
      target genes. Combinations of MIMs, exemplified by the SCL/LMO2 complexes, which
      have variable content and binding sites, explain how individual regulators can
      have different targets in HSCs and erythroid cells and possibly also how HSCs
      maintain stem cell functions while expressing lineage-affiliated genes at low
      level, so-called multi-lineage priming. MIMs combined with cross-antagonism
      describe the relationship between PU.1 and GATA-1 and between two of their target
      genes, Fli-1 and EKLF, with victory for GATA-1 and EKLF leading to erythroid
      lineage specification. These GRNs are useful repositories for current regulatory
      information, are accessible in interactive form via the internet, enable the
      consequences of perturbation to be predicted, and can act as seed networks to
      organize the rapidly accumulating microarray data.

PMID- 16626683
TI  - CNBP regulates forebrain formation at organogenesis stage in chick embryos.
AB  - We recently demonstrated that Cellular Nucleic acid Binding Protein (CNBP)(-/-)
      mouse embryos exhibit forebrain truncation due to a lack of proper morphogenetic
      movements of the anterior visceral endoderm (AVE) during pre-gastrulation stage
      (Chen, W., Liang, Y., Deng, W., Shimizu, K., Ashique, A.M., Li, E., Li, Y.P.,
      2003. The zinc-finger protein CNBP is required for forebrain formation in the
      mouse, Development 130, 1367-1379). However, CNBP expression pattern in the mouse
      forebrain suggests that CNBP may have more direct effects during forebrain
      development. Our data show that CNBP is expressed in tissues of early chick
      embryo that are the equivalent to the mouse embryo. Using a combination of RNAi
      silencing and Retrovirus-misexpression approaches, we investigated the temporal
      function of CNBP in the specification/development of the chick forebrain during
      organogenesis. The silencing of CNBP expression resulted in forebrain truncation
      and the absence of BF-1, Six3 and Hesx1 expression, but not Otx2 in chick
      embryos. Misexpression of CNBP induced the expression of BF-1, Six3 and Hesx1 in
      the hindbrain, but not the expression of Otx2. These results offer novel insights
      into the function of CNBP during organogenesis as the regulator of forebrain
      formation and a number of rostral head transcription factors. Moreover, CNBP and
      Otx2 may play roles as regulators of forebrain formation in two parallel
      pathways. These new insights into CNBP functions underscore the essential role of
      CNBP in forebrain formation during chick embryo organogenesis.

PMID- 16626684
TI  - Global cell sorting in the C. elegans embryo defines a new mechanism for pattern
      formation.
AB  - 4D microscopic observations of Caenorhabditis elegans development show that the
      nematode uses an unprecedented strategy for development. The embryo achieves
      pattern formation by sorting cells, through far-ranging movements, into coherent
      regions before morphogenesis is initiated. This sorting of cells is coupled to
      their particular fate. If cell identity is altered by experiment, cells are
      rerouted to positions appropriate to their new fates even across the whole
      embryo. This cell behavior defines a new mechanism of pattern formation, a
      mechanism that is also found in other animals. We call this new mechanism "cell
      focusing". When the fate of cells is changed, they move to new positions which
      also affect the shape of the body. Thus, this process is also important for
      morphogenesis.

PMID- 16626685
TI  - Global cell sorting is mediated by local cell-cell interactions in the C. elegans
      embryo.
AB  - The Caenorhabditis elegans embryo achieves pattern formation by sorting cells
      into coherent regions before morphogenesis is initiated. The sorting of cells is
      coupled to their fate. Cells move extensively relative to each other to reach
      their correct position in the body plan. Analyzing the mechanism of cell sorting
      in in vitro culture experiments using 4D microscopy, we show that all AB-derived
      cells sort only according to their local neighbors, and that all cells are able
      to communicate with each other. The directions of cell movement do not depend on
      a cellular polarity but only on local cell-cell interactions; in experimental
      situations, this allows even the reversal of the polarity of whole regions of the
      embryo. The work defines a new mechanism of pattern formation we call "cell
      focusing".

PMID- 16626686
TI  - Retinoic acid induces neurite outgrowth and growth cone turning in invertebrate
      neurons.
AB  - Identification of molecules involved in neurite outgrowth during development
      and/or regeneration is a major goal in the field of neuroscience. Retinoic acid
      (RA) is a biologically important metabolite of vitamin A that acts as a trophic
      factor and has been implicated in neurite outgrowth and regeneration in many
      vertebrate species. Although abundant in the CNS of many vertebrates, the precise
      role of RA in neural regeneration has yet to be determined. Moreover, very little
      information is available regarding the role of RA in invertebrate nervous
      systems. Here, we demonstrate for the first time that RA induces neurite
      outgrowth from invertebrate neurons. Using individually identified neurons
      isolated from the CNS of Lymnaea stagnalis, we demonstrated that a significantly
      greater proportion of cells produced neurite outgrowth in RA. RA also extended
      the duration of time that cells remained electrically excitable in vitro, and we
      showed that exogenously applied RA acted as a chemoattractive factor and induced
      growth cone turning toward the source of RA. This is the first demonstration that
      RA can induce turning of an individual growth cone. These data strongly suggest
      that the actions of RA on neurite outgrowth and cell survival are highly
      conserved across species.

PMID- 16626687
TI  - Suramin-induced reciprocal changes in glucose and lactate synthesis in renal
      tubules contribute to its hyperglycaemic action.
AB  - Suramin is the drug of choice for the treatment of African trypanosomiasis and
      onchocerciasis. It is also tested for its potential use as an anticancer agent
      and chemosensitizer. As suramin has been reported to induce hyperglycaemia, its
      effect on glucose formation has been studied in isolated rabbit hepatocytes and
      kidney-cortex tubules. In contrast to hepatocytes, in kidney-cortex tubules
      suramin augments glucose production and decreases lactate formation. Suramin
      induced changes in intracellular gluconeogenic/glycolytic intermediates indicate
      a decrease in flux through pyruvate-phosphoenolpyruvate step. Moreover, this
      compound diminishes pyruvate kinase activity in kidney-cortex cytosolic fraction,
      while fructose-1,6-bisphosphate ameliorates its inhibitory action. As (i) kidneys
      are important contributors to the whole body glucose homeostasis and (ii) suramin
      is known to accumulate in kidney, suramin-induced stimulation of glucose
      formation in renal tubules might be responsible for hyperglycaemia observed in
      patients undergoing suramin treatment.

PMID- 16626688
TI  - 18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus
      to decrease morphine self-administration in rats.
AB  - The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative
      anti-addictive agent that has been shown, in rats, to decrease the self
      administration of morphine and other drugs of abuse. Previous work has
      established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors.
      Because alpha3beta4 nicotinic receptors in the brain are preferentially located
      in the medial habenula and the interpeduncular nucleus, the present study was
      conducted to determine if 18-MC could act in these brain areas to modulate
      morphine self-administration in rats. Local administration of 18-MC into either
      the medial habenula or the interpeduncular area decreased morphine self
      administration while having no effect on responding for a non-drug reinforcer
      (sucrose). Similar results were produced by local administration into the same
      brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and
      alpha-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental
      area had no effect on morphine self-administration. These and other data are
      consistent with the hypothesis that 18-MC decreases morphine self-administration
      by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular
      pathway.

PMID- 16626689
TI  - Picrotoxin blocks the anxiolytic- and panicolytic-like effects of sodium
      valproate in the rat elevated T-maze.
AB  - The effect of acute sodium valproate administration, an anxiolytic and putative
      panicolytic drug, was evaluated in rats tested in the elevated T-maze, an animal
      model that measures two defensive reactions: avoidance (inhibitory avoidance),
      related to generalized anxiety, and escape (escape from open arms), related to
      panic. Additionally, the involvement of gamma-aminobutyric acid (GABA)
      neurotransmission in sodium valproate effects was studied by picrotoxin co
      administration. Sodium valproate (300 mg/kg, intraperitoneally, 30 min before the
      test) impaired both avoidance latency (time to leave the closed arm) and one-way
      escape (latency to enter the closed arm) indicating anxiolytic and panicolytic
      effects, respectively. Pre-treatment with picrotoxin (0.5 mg/kg,
      intraperitoneally, 5 min before sodium valproate administration) blocked the
      effects of sodium valproate on inhibitory avoidance and one-way escape. No
      locomotor effect was seen in the open-field. These data suggest that sodium
      valproate exerts anxiolytic-like and panicolytic-like effects in the elevated T
      maze and that these effects were mediated by picrotoxin-sensitive GABA type A
      receptors.

PMID- 16626690
TI  - Effect of melatonin on enzyme activities of glutathione reductase from human
      erythrocytes in vitro and from rat erythrocytes in vivo.
AB  - The in vivo and in vitro effects of melatonin on enzyme activity of glutathione
      reductase (Glutathione: NADP(+) oxidoreductase, EC 1.8.1.7; GR) were investigated
      in this study. Glutathione reductase was purified from human erythrocytes 5.823
      fold with a yield of 24% by ammonium sulfate fractionation, affinity
      chromatography on 2',5'-ADP Sepharose 4B and gel filtration chromatography on
      Sephadex G-200. Enzyme activity was determined by the Calberg and Mannervik
      method using a spectrophotometer at 340 nm. For in vitro experiments, the enzyme
      activity increased at 0.02 mM and decreased at 0.08 mM melatonin concentration
      and reached a plateau above 0.08 mM. Melatonin was administered 10 mg/kg
      intraperitoneally (ip) and had a stimulatory effect on the enzyme. In vivo
      studies were performed for melatonin in Sprague-Dawley rats and time-dependent
      effects were demonstrated. Glutathione reductase activity in erythrocytes was
      increased more by melatonin at 1 and 3 h. These results indicate that
      pharmacological levels of melatonin increased enzyme activity in erythrocytes.
      They also indicate that melatonin may be pharmacologically useful in patients
      with a deficiency of the enzyme in red blood cells causing hemolytic anemia.

PMID- 16626691
TI  - Noradrenaline-induced increases in calcium and tension in skeletal muscle
      conductance and resistance arteries from rats with post-infarction heart failure.
AB  - We tested the hypothesis that arterial reactivity to noradrenaline is augmented
      in congestive heart failure (CHF), which could contribute to the deleterious
      changes in peripheral vascular resistance and compliance in this condition. From
      male Wistar rats with post-infarction CHF and sham-operated rats, skeletal muscle
      conductance and resistance arteries (mean lumen diameters: 514 and 186 microm)
      were isolated and mounted on wire myographs, and wall tension was recorded in
      response to cumulative application of acetylcholine and noradrenaline to the
      vessel segments. In a subset of experiments, wall tension and cytosolic free
      calcium ion concentration [Ca(2+)](i) were recorded simultaneously during
      noradrenaline application, using wire myography and the FURA-2 technique. No
      significant differences were found in the arterial baseline levels of [Ca(2+)](i)
      or tension between CHF and sham rats. In the resistance arteries of CHF rats, the
      noradrenaline-induced increases in [Ca(2+)](i) were significantly enhanced
      (P=0.003). Despite the augmented [Ca(2+)](i) levels, the tension responses to
      noradrenaline were unaltered in these arteries. In the conductance arteries,
      there were no significant differences in noradrenaline-induced [Ca(2+)](i) or
      tension responses between CHF and control rats. CHF did not alter vascular
      morphology or change vascular relaxations to acetylcholine in either type of
      artery. In conclusion, these results do not support the contention that arterial
      reactivity to noradrenaline is augmented in the skeletal muscle vascular bed in
      CHF. On the contrary, the unchanged contractile responsiveness in the resistance
      arteries despite the enhanced levels of [Ca(2+)](i) during noradrenaline
      application suggests that the contractile function of these vessels is
      compromised in CHF. Neither vascular remodeling, endothelial dysfunction nor
      changes in baseline vascular tone could be demonstrated in the skeletal muscle
      vascular bed of this animal model of heart failure.

PMID- 16626692
TI  - Nicotine-induced conditioned taste aversion in the rat: effects of ethanol.
AB  - It has been shown that small doses of ethanol antagonise the discriminative
      stimulus properties of nicotine in the rat. The aim of the present study was to
      evaluate whether ethanol could antagonise the aversive stimulus effects of
      nicotine. Wistar rats were trained to associate nicotine injections with a novel
      tasting fluid (0.1% saccharin) in the conditioned taste aversion procedure.
      Nicotine (0.3 mg/kg, s.c.) was injected 5 min after the end of a 20-min exposure
      to the saccharin solution. Ethanol (0.25-0.5 g/kg, i.p.) was administered 5 or 50
      min before nicotine. In general, ethanol did not inhibit nicotine-induced
      conditioned taste aversion. Contrary to the findings in drug discrimination
      studies, a slight but significant enhancement of nicotine-induced taste aversion
      conditioning was observed after ethanol pre-treatment. Blood ethanol levels were
      measured in a separate group of rats. Maximal blood ethanol levels after i.p.
      administration of 0.25 or 0.5 g/kg ethanol exceeded 20 and 80 mg%, respectively.
      Concluding, the present results may indicate that ethanol does not attenuate
      nicotine-induced conditioned taste aversion in the rat.

PMID- 16626693
TI  - Cholesterol-lowering effect of platycodin D in hypercholesterolemic ICR mice.
AB  - This study investigates the in vivo hypocholesterolemic action of platycodin D
      and its in vitro evidence for the cholesterol-lowering properties. In order to
      examine the effects of platycodin D on hypercholesterolemia in male ICR mice,
      platycodin D with doses of 15, 30 or 50 mg/kg was orally administered for 8
      weeks. Changes in body weight and daily food intake were measured regularly
      during the experimental period. Final contents of triglyceride and different
      types of cholesterol in the serum, livers and feces were determined. The effects
      of platycodin D on cholesterol metabolism were further investigated with several
      in vitro assays, including antioxidant effect on low density lipoprotein
      oxidation, inhibition of human acyl-coenzyme A:cholesterol acyltransferase
      (hACAT) and serum lipoprotein associated-phospholipase A(2) (Lp-PLA(2)), as well
      as the regulation of farnesoid X receptor. The formation of insoluble complex
      between platycodin D and cholesterol was also investigated. Following an eight
      week experimental period, the body weights of platycodin D-fed mice were less
      than those of control mice on a high cholesterol diet by 11.2+/-5% (P<0.01) with
      15 mg/kg platycodin D, 11.7+/-5% (P<0.01) with 30 mg/kg platycodin D, and 23.4+/
      7.9% (P<0.0001) with 50 mg/kg platycodin D, respectively. A decrease in daily
      food consumption was also noted in most of the treated animals. Triglyceride and
      cholesterol concentrations were decreased in serums and livers, but increased in
      feces. Some of the in vitro observations revealed that the hypocholesterolemic
      effect of platycodin D is partly associated with inhibition to hACAT activity and
      antagonism to the farnesoid X receptor as well as the formation of insoluble
      complex with between platycodin D and cholesterol. Both in vivo and in vitro
      results demonstrate a potential value of platycodin D as a novel cholesterol
      lowering and anti-atherogenic candidate.

PMID- 16626694
TI  - Inhibitory effects of alendronate on cholinergic responses in rat lower
      esophageal sphincter.
AB  - Alendronate is a potent inhibitor of osteoclast-mediated bone resorption, but its
      use results in serious esophageal damage. In order to clarify the latter, we
      examined the effects of alendronate on electrical field stimulation-induced
      responses in the rat lower esophageal sphincter. Electrical field stimulation
      induced atropine-sensitive contraction. Alendronate inhibited electrical field
      stimulation-induced contraction in a concentration-dependent manner. In the
      presence of N(G)-nitro-L-arginine (L-nitroarginine), electrical field stimulation
      elicited a strong cholinergic contraction. This contraction was also inhibited by
      alendronate, to a similar extent as that seen in the absence of L-nitroarginine.
      In lower esophageal sphincter contracted by prostaglandin F(2alpha) and treated
      with atropine, electrical field stimulation induced L-nitroarginine-sensitive
      relaxation. Alendronate did not affect relaxation. These results suggest that
      alendronate decreases the tone of lower esophageal sphincter by inhibiting
      cholinergic nervous activity.

PMID- 16626695
TI  - Importance of ryanodine receptors in effects of cyclic GMP is reduced in
      thyroxine-induced cardiac hypertrophy.
AB  - We tested the hypothesis that the negative functional effects of cyclic GMP were
      mediated by ryanodine receptors, and that these effects would be reduced in
      thyroxine (thyroxine, 0.5 mg/kg/day, 16 days)-induced hypertrophic myocytes.
      Using rabbit ventricular myocytes from control (n=9) and thyroxine (n=9) hearts,
      percent cell shortening (%) and maximum rate of contraction and relaxation were
      determined using a video edge detector at baseline and after 10(-6), 10(-5) M 8
      bromo-cyclic GMP. Dantrolene 10(-6) M, ryanodine receptor inhibitor, was added
      alone or after 8-Br-cGMP treatment. Changes in cytosolic Ca(2+) concentration
      were assessed in fura-2-loaded control and thyroxine myocytes. 8-Br-cGMP caused a
      significant decrease in percent shortening, from 5.3+/-0.9% to 3.9+/-0.6% at 10(
      5 )M in control, and 3.4+/-0.3% to 2.6+/-0.4% in thyroxine myocytes. Dantrolene
      significantly decreased percent shortening from 4.5+/-0.8% to 3.7+/-0.1% in
      control and from 3.7+/-0.1% to 2.8+/-0.3% in thyroxine myocytes. In 8-Br-cGMP
      treated control myocytes, dantrolene did not significantly change myocyte
      contractility, which suggested that cyclic GMP acted on ryanodine receptors.
      However, in 8-Br-cGMP treated thyroxine myocytes, dantrolene further reduced
      myocyte contractility implying that the interaction of cyclic GMP and ryanodine
      receptors appeared to be interrupted in thyroxine myocytes. Maximum rate of
      contraction data were consistent with the percent cell shortening data and Ca(2+)
      transients changed similarly to myocyte contractility. We conclude that effects
      of cyclic GMP on myocytes contractility were partially mediated though
      interaction with ryanodine receptors and the subsequent decrease in cytosolic
      calcium levels. This interaction was reduced in thyroxine hypertrophic myocytes.

PMID- 16626696
TI  - Paradoxical effects of very low dose MK-801.
AB  - Systemic injection of the noncompetitive NMDA (N-methyl-D-aspartate) receptor
      antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion
      and various stereotypic behaviors in rodents. However, the MK-801 dose ranges
      commonly examined usually begin at tenth of mg/kg and going higher, with the
      implicit assumption of lower doses being ineffective. We report here that very
      low dose MK-801, well below the commonly studied doses, exert distinct effects on
      rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has
      strikingly different effects than higher doses commonly reported in the
      literature. Locomotion, rearing, grooming, and other behaviors are strongly
      inhibited, replaced by periods of immobility. This is in contrast to the mobility
      enhancing effect of MK-801 at commonly reported dose ranges. The effects of very
      low dose MK-801 are qualitatively similar to those observed with moderate doses
      (0.1-0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight
      the complexity of the dose-response relation for MK-801-induced behaviors.

PMID- 16626697
TI  - Effect of melatonin and vitamin E on diabetes-induced learning and memory
      impairment in rats.
AB  - Previous studies indicate that diabetes mellitus might be accompanied by a
      certain erosion of brain function such as cognitive impairment. The aim of this
      study was to examine and compare the effects of melatonin and vitamin E on
      cognitive functions in diabetic rats. Diabetes was induced in male albino rats
      via intraperitoneal streptozotocin injection. Learning and memory behaviors were
      investigated using a spatial version of the Morris water maze test. The levels of
      lipid peroxidation and glutathione were detected in hippocampus and frontal
      cortex. The diabetic rats developed significant impairment in learning and memory
      behaviors as indicated by the deficits in water maze tests as compared to control
      rats. Furthermore, lipid peroxidation levels increased and glutathione
      concentration decreased in diabetic rats. Treatment with melatonin and vitamin E
      significantly ameliorated learning and memory performance. Furthermore, both
      antioxidants reversed lipid peroxidation and glutathione levels toward their
      control values. These results suggest that oxidative stress may contribute to
      learning and memory deficits in diabetes and further suggest that antioxidant
      melatonin and vitamin E can improve cognitive impairment in streptozotocin
      induced diabetes.

PMID- 16626698
TI  - Pairing of heterochromatin in response to cellular stress.
AB  - We previously reported that exposure of human cells to DNA-damaging agents (X
      rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric
      heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and
      also heat shock treatment of human cells lead to similar effects. Since the
      various agents induce very different types and frequencies of damage to cellular
      constituents, the data suggest a general stress response as the underlying
      mechanism. Moreover, local UV irradiation experiments revealed that pairing of
      heterochromatin is an event that can be triggered without induction of DNA damage
      in the heterochromatic sequences. The repair deficient xeroderma pigmentosum
      cells (group F) previously shown to fail pairing after MMC displayed elevated
      pairing after heat shock treatment but not after UV exposure. Taken together, the
      present results indicate that pairing of heterochromatin following exposure to
      DNA-damaging agents is initiated by a general stress response and that the
      sensing of stress or the maintenance of the paired status of the heterochromatin
      might be dependent on DNA repair.

PMID- 16626699
TI  - Functional abnormalities in the retinal pigment epithelium of CFTR mutant mice.
AB  - In response to light, the mouse retinal pigment epithelium (RPE) generates a
      series of slow changes in potential that are referred to as the c-wave, fast
      oscillation (FO) and light peak (LP) of the electroretinogram (ERG). While the FO
      is known to reflect a Cl(-) conductance generated at the basal membrane of the
      RPE, the specific channel (s) underlying this potential has not been identified.
      In the present study we examined two strains of mice with cftr mutations to
      define the contribution that cystic fibrosis transmembrane regulator (CFTR)
      mediated Cl(-) conductance makes to the mouse ERG. Responses obtained from
      cftr(Delta508/Delta508) mice exhibited an overall reduction in all components
      generated by the RPE in response to light without alteration of the luminance
      response function. Responses obtained from cftr(-/-) mice were also reduced in
      amplitude. These results illustrate the usefulness of ERG analysis of mice
      deficient in ion channels that are expressed in the RPE, and indicate that CFTR
      contributes to the generation of RPE-driven ERG components, but that it is not
      the sole generator of any one of these components.

PMID- 16626700
TI  - Multiple, parallel cellular suicide mechanisms participate in photoreceptor cell
      death.
AB  - Photoreceptor degeneration in human photoreceptor dystrophies and in the relevant
      animal models has been thought to be executed by one common mechanism -- caspase
      mediated apoptosis. However, recent experiments have challenged this concept. In
      previous experiments, analyzing gene expression in the degenerating rd/rd mouse
      retina, we have suggested that the gene defect leads to oxidative stress and
      altered metabolism, which may induce caspase-dependent and caspase-independent
      cell death mechanisms such as the activation of cystein-proteases, lysosomal
      proteases, autophagy and complement-mediated lysis. In this study we asked two
      questions. First, whether a temporal analysis of these different mechanisms
      during the course of degeneration would enable us to establish a causal
      relationship between these events; and second, whether photoreceptor degeneration
      in different models of photoreceptor dystrophies occurs by activating the same
      mechanisms. Three models of photoreceptor degeneration were chosen in which
      photoreceptor degeneration is caused by different events: the rd/rd mouse
      (calcium overload); the rds/rds mouse (structural defect); and light-damage (LD;
      oxidative stress). Marker genes were selected for the identified processes. PCR
      analysis on laser capture microdissection samples was used to verify the
      expression of these genes in the rod photoreceptor layer. A temporal relationship
      between the processes was established at the mRNA level, using quantitative RT
      PCR. The time course of gene expression was compared to that of cell loss (loss
      of rows of photoreceptor nuclei) and apoptosis (TUNEL labeling). Apoptosis and
      autophagy was analyzed using enzymatic assays. The time course of apoptosis and
      TUNEL labeling coincide in all three models. Complement-activated lysis was found
      to either parallel (rd/rd and rds/rds) or precede (LD) the development of TUNEL
      positive cells. Autophagy was determined to parallel (rd/rd and LD) or lag
      (rds/rds) behind the development of TUNEL-positive cells. In all three models,
      glucose metabolism was found to be increased significantly prior to the onset of
      cell death, but then dropped in parallel with the loss of cells. The presence of
      the marker genes was verified by laser capture microdissection, and apoptosis
      (caspase activity) and autophagy (lysozyme and cathepsin activity) were verified
      in retina extracts. These results provide evidence that irrespective of whether
      photoreceptor degeneration is triggered by gene defects (lack of beta-PDE or
      rds/peripherin) or environmental stress (light-damage), a number of pro-apoptotic
      mechanisms are triggered leading to the degeneration of the photoreceptor cells.
      The temporal pattern of the different pathways suggests that the non-caspase
      dependent mechanisms may actively participate in the demise of the
      photoreceptors, rather than represent a passive response of the retina to the
      presence of dying cells. Thus, unless the common upstream initiator for a given
      photoreceptor dystrophy is found, multiple rescue paradigms need to be used to
      target all active pathways.

PMID- 16626701
TI  - Focus on molecules: FoxE3.

PMID- 16626702
TI  - Development of inner retinal function, evidenced by the pattern
      electroretinogram, in the rat.
AB  - Though the rat is increasingly used as an animal model in ophthalmic research,
      including the study of glaucoma, little is known about age-related changes in its
      inner retinal function. The aim of this study was to evaluate these changes in
      the rat during the first 18 weeks of life. The pattern electroretinogram (PERG)
      was used to monitor inner retinal activity in 16 developing rats. In each animal,
      recordings were conducted at ages 3, 5, 7, 11, 14 and 18 weeks to assess age
      related changes in function. Signals were evoked by five stimuli of progressively
      increasing check width (subtending 82-1312 arc minutes of visual angle) that were
      projected directly onto the fundus through a specially modified ophthalmoscope
      which allowed visual and manual control of stimulus quality. Poor signal:noise
      ratio prevented signal analysis at age 3 weeks. Subsequently, PERG amplitude
      increased significantly, up to 242% (depending on stimulus check width), during
      weeks 5-11. After peaking at 11 weeks, signal amplitude declined moderately.
      Signal latency mirrored that of amplitude, decreasing during the first 11 weeks,
      and then increasing steadily. Latency was not affected by stimulus check width.
      Age was highly correlated with P1 latency (R(2)=0.80) and moderately correlated
      with N2 latency (R(2)=0.52). Therefore, we propose that studies of inner retinal
      diseases (such as glaucoma) in the rat model should use age-matched controls, as
      electrophysiological results may be confounded by age-related changes. The rat
      PERG undergoes many of the age-related changes that have been reported in humans,
      and thus may serve as an animal model to study development of inner retinal
      function.

PMID- 16626703
TI  - Focus on molecules: cystatin C.

PMID- 16626704
TI  - Transcriptional changes in multiple system atrophy and Parkinson's disease
      putamen.
AB  - Multiple system atrophy (MSA) and sporadic, non-mendelian Parkinson's disease
      (PD) are progressive neurodegenerative disorders with overlapping clinical
      symptoms and pathology. The etiology of both disorders is unknown, and complex
      combinations of multiple susceptibility genes and environmental factors are
      thought to be involved. Both disorders are characterized by ubiquitous alpha
      synuclein aggregates in distinct regions and cell types of the central nervous
      system. In PD, alpha-synuclein-positive aggregates appear to be largely neuronal
      while in MSA oligodendroglial inclusions prevail. In PD patients, the alpha
      synuclein pathology is thought to evolve in a rather regular pattern, starting in
      the brainstem and olfactory bulb and extending gradually onto the substantia
      nigra and ultimately the cerebral cortex while the cerebellum is largely spared.
      MSA pathology has not been graded in a similar way yet; neuropathological
      analyses revealed neurodegeneration and gliosis primarily in the brainstem,
      midbrain and basal ganglia and the cerebellum, while the cortex is largely
      spared. To identify disease-specific transcriptional patterns in MSA, we chose
      CNS regions differentially affected in MSA and PD for comparative gene expression
      profiling: putamen, cerebellum and occipital cortex. Four genes were regulated in
      both MSA and PD putamen and twelve in MSA and PD cerebellum. Regulated
      transcripts were validated using real-time quantitative RT-PCR, and
      immunohistochemistry was performed for the most significantly downregulated
      transcripts in MSA and PD putamen, GPR86 and RGS14, associated with G protein
      signaling and transcriptional regulation.

PMID- 16626705
TI  - Transplanted adult neural progenitor cells survive, differentiate and reduce
      motor function impairment in a rodent model of Huntington's disease.
AB  - The present study investigated the ability for adult rat neural progenitor cells
      to survive transplantation, structurally repopulate the striatum and improve
      motor function in the quinolinic acid (QA) lesion rat model of Huntington's
      disease. Neural progenitor cells were isolated from the subventricular zone of
      adult Wistar rats, propagated in culture and labeled with BrdU (50 microM).
      Fourteen days following QA lesioning, one group of rats (n = 12) received a
      unilateral injection of adult neural progenitor cells ( approximately 180,000
      cells total) in the lesioned striatum, while a second group of rats (n = 10)
      received a unilateral injection of vehicle only (sham transplant). At the time of
      transplantation adult neural progenitor cells were phenotypically immature, as
      demonstrated by SOX2 immunocytochemistry. Eight weeks following transplantation,
      approximately 12% of BrdU-labeled cells had survived and migrated extensively
      throughout the lesioned striatum. Double-label immunocytochemical analysis
      demonstrated that transplanted BrdU-labeled progenitor cells differentiated into
      either astrocytes, as visualized by GFAP immunocytochemistry, or mature neurons,
      demonstrated with NeuN. A proportion of BrdU-labeled cells also expressed DARPP
      32 and GAD67, specific markers for striatal medium spiny projection neurons and
      interneurons. Rats transplanted with adult neural progenitor cells also
      demonstrated a significant reduction in motor function impairment as determined
      by apomorphine-induced rotational asymmetry and spontaneous exploratory forelimb
      use when compared to sham transplanted animals. These results demonstrate that
      adult neural progenitor cells survive transplantation, undergo neuronal
      differentiation with a proportion of newly generated cells expressing markers
      characteristic of striatal neurons and reduce functional impairment in the QA
      lesion model of Huntington's disease.

PMID- 16626706
TI  - Murine embryonic EGF-responsive ventral mesencephalic neurospheres display
      distinct regional specification and promote survival of dopaminergic neurons.
AB  - Similar to embryonic forebrain, the embryonic mesencephalon contains Fibroblast
      Growth Factor 2 (FGF2)- and Epidermal Growth Factor (EGF)-responsive progenitors
      that can be isolated as neurospheres. Developmentally, the FGF2-responsive
      population appears first and is thought to give rise to EGF-responsive neural
      stem cells. It is not known whether following this developmental switch of growth
      factor responsiveness ventral mesencephalic (VM)-derived neural stem cells
      display distinct region-specific properties. We found that murine VM- and dorsal
      mesencephalic (DM)-derived primary neurospheres isolated with EGF at embryonic
      day 14.5 differed with respect to neurosphere formation efficacy and size. VM-
      but not DM-derived spheres expressed En1, the molecular marker of isthmic
      organizer, and contained transcripts of BDNF, FGF2, IGF-I and NT-3. Both VM and
      DM primary neurospheres were self-renewing and gave rise to astroglial cells, but
      20% of VM spheres also generated neurons. According to in vitro properties, DM-
      and majority of VM-derived EGF-responsive progenitors represent glial precursors.
      VM- but not DM-derived primary neurospheres enriched their respective conditioned
      medium with factors that promoted the survival of dopaminergic neurons in vitro,
      suggesting that ventral mesencephalic EGF-responsive progenitors are endowed with
      the potential to provide trophic support to nearby nascent dopaminergic neurons.
      These data may have implications in the treatment of Parkinson's disease.

PMID- 16626707
TI  - Postnatal development of vibrissae motor output following neonatal infraorbital
      nerve manipulation.
AB  - Using the model of infraorbital nerve (IoN) injury, we have studied the role IoN
      signals have on the developing vibrissal motor system. To this end, in ten rats,
      the IoN was severed on the day of birth: in five rats, the IoN was repaired to
      promote axon regeneration (Reinnervated group) while axon regeneration was
      prevented in the remaining five rats (Deafferented group). In another five rats,
      the isolated IoN was left intact (Sham group) and still another group of five
      rats was left untouched (Control group). After these rats had reached adulthood,
      the compound muscle action potential (MAP) was recorded from the vibrissa muscle
      and intracortical microstimulation (ICMS)-evoked movements were mapped in the
      frontal cortex contralateral to the operated side. We found: (i) no difference
      between Control, Sham and Reinnervated groups in the integrated MAPs and in the
      size and excitability of the M1 vibrissal representation. (ii) the Deafferented
      group showed a 42.9% decrease in the integrated MAP plus a 47.2% and 36.9%
      reduction, respectively, in the size and excitability of the M1 vibrissae
      representation. We conclude that, during perinatal life, IoN signals regulate the
      development of both the peripheral and central vibrissal motor system and that
      IoN reinnervation restores sensory signals able to stabilize normal development
      of the vibrissal motor system.

PMID- 16626708
TI  - Role of oxidative stress on beta-amyloid neurotoxicity elicited during impairment
      of energy metabolism in the hippocampus: protection by antioxidants.
AB  - Age-associated oxidative stress has been implicated in neuronal damage linked
      with Alzheimer's disease (AD). In addition to the role of beta-amyloid peptide
      (Abeta) in the pathogenesis of AD, reduced glucose oxidative metabolism and
      decreased mitochondrial activity have been suggested as associated factors.
      However, the relationship between Abeta toxicity, metabolic impairment, and
      oxidative stress is far from being understood. In vivo neurotoxicity of Abeta25
      35 peptide has been conflicting. However, in previous studies, we have shown that
      Abeta25-35 consistently induces synaptic toxicity and neuronal death in the
      hippocampus in vivo, when administered during moderate glycolytic or
      mitochondrial inhibition. In the present study, we have investigated whether
      enhancement of Abeta neurotoxicity during these conditions involves oxidative
      stress. Results show increased lipoperoxidation (LPO) when Abeta is administered
      in the hippocampus of rats previously treated with the glycolysis inhibitor,
      iodoacetate. Neuronal damage and LPO are efficiently prevented by vitamin E,
      while the spin trapper, alpha-phenyl-N-tert-butyl nitrone, shows partial
      protection. Abeta stimulates LPO in synaptosomes, but toxicity is only observed
      in the presence of metabolic inhibitors. Damage and LPO are efficiently prevented
      by vitamin E. The present results suggest an interaction between oxidative stress
      and metabolic impairment in the Abeta neurotoxic cascade.

PMID- 16626709
TI  - Social and photoperiod effects on reproduction in five species of Peromyscus.
AB  - At temperate latitudes, mammals and birds use changes in day length to time their
      reproductive activities to coincide with seasonal fluctuations in the
      environment. Close to the equator, however, conditions permissive of breeding do
      not track changes in day length as well, so other cues may be more important than
      photoperiod. In a variety of vertebrates, social interactions regulate breeding
      condition. We hypothesized that individuals of different species of Peromyscus
      mice found closer to the equator would respond more strongly to housing with an
      opposite sex conspecific than they would to photoperiod. To test this hypothesis,
      we compared the effects of long and short day lengths versus 8 days of pair
      housing with a female on reproductive tissue weights and testosterone (T)
      concentrations in five species of Peromyscus (P. aztecus, P. eremicus, P.
      maniculatus, P. melanophrys, and P. polionotus). After 13 weeks of short days
      (8L:16D), P. maniculatus, P. melanophrys, and P. polionotus significantly reduced
      relative testes mass compared to long day (16L:8D) housed animals. Social
      housing, however, had no effect on tissue weights in any species. However, male
      P. polionotus paired with females for 8 days increased T concentrations compared
      to single-housed males, whereas paired P. maniculatus reduced T. These data
      suggest that mechanisms of photoperiodic and social regulation of reproductive
      function are mediated by different physiological mechanisms among closely-related
      species and that both phylogeny and environmental factors contribute to patterns
      of reproductive plasticity.

PMID- 16626710
TI  - The relationship between social status, behaviour, growth and steroids in male
      helpers and breeders of a cooperatively breeding cichlid.
AB  - We tested whether subordinate helper males of the Lake Tanganyika cooperatively
      breeding cichlid Neolamprologus pulcher show elevated excretion levels of the
      stress hormone cortisol and reduced levels of 11-ketotestosterone and
      testosterone when living in groups with a small breeder male, compared to similar
      helper males living in groups with a large breeder male, in a full-factorial
      repeated measures experimental design. We also measured the same hormones in
      breeder males with and without helper males. Previous research showed that the
      size difference between large male helpers and male breeders in groups of this
      species influences behaviour and growth decisions. Contrary to our expectation,
      no effect of the size-difference between helper males and breeder males on helper
      hormone levels was detected. Furthermore, helper males had similar hormone
      excretion levels to those of size-matched breeder males without helpers, and to
      small breeder males. There was no influence of egg laying on breeder male and
      helper hormone levels during the experiment. Interestingly, all three hormone
      levels were significantly lower in helpers showing elevated levels of submissive
      behaviour towards the breeders, independently of the size of the breeder males.
      The low cortisol levels suggest that helper males can successfully reduce stress
      by appeasing breeder males through submission. Furthermore, helper males showing
      a high level of submissive behaviour had lower levels of androgens than less
      submissive helpers, suggesting a lower reproductive potential in submissive
      helpers. We propose that helper submission may be used as an honest signal of
      reduced interest in reproduction towards the breeder male in this species.

PMID- 16626711
TI  - Paraparesis with complete recovery in antepartum eclampsia.

PMID- 16626712
TI  - Tubal ligation via posterior colpotomy.

PMID- 16626714
TI  - Co-stimulatory molecule OX40 ligand in early human pregnancy.

PMID- 16626713
TI  - Pregnancy outcomes in women with or without placental malaria infection.
AB  - OBJECTIVE: To assess delivery outcomes in women with placental malaria who
      presented at public hospitals in Kisumu, a holoendemic region in western Kenya.
      METHODS: A cross-sectional study using both histology and molecular biology was
      conducted with 90 consecutive pregnant women who presented at 3 hospitals during
      a 2-week period. Data collectors completed standardized questionnaires using each
      patient's hospital record and physical examination results, and registered birth
      indices such as weight, head circumference, and weight-head ratio. Malaria
      infection of the placenta was assessed using a molecular biology approach (for
      genomic differences among parasite species) as well as histology techniques. Of
      the 5 histologic classes of placental infection, class 1 corresponds to active
      infection and class 4 to past infection; class 2 and 3 to active chronic
      infection; and class 5 to uninfected individuals. Plasmodium species typing was
      determined by polymerase chain reaction amplification of the parasite's genome.
      RESULTS: In newborns at term, low birth weight was directly associated with
      classes 2 and 4 of placental infection (P = 0.053 and P = 0.003, respectively),
      and differences in birth weight remained significant between the 5 classes (P <
      0.001) even after adjusting for parity and mother's age. Plasmodium falciparum
      was the only detected parasite. CONCLUSIONS: In Kisumu, infection with P.
      falciparum is an important cause of low birth weight and morbidity when it is
      associated with histologic classes 2 and 4 of placental infection. Moreover,
      polymerase chain reaction assays should be supported by ministries of health as
      an ancillary method of collecting data for malaria control during pregnancy and
      providing a baseline for future interventions.

PMID- 16626715
TI  - Early versus late closure of vesicovaginal fistulas.

PMID- 16626716
TI  - Effects of gestational weight gain and body mass index on obstetric outcome in
      Sweden.
AB  - OBJECTIVE: The objective of this study was to estimate the effects of low and
      high gestational weight gain, in different maternal Body Mass Index (BMI)
      classes, on obstetric and neonatal outcomes. METHOD: A prospective population
      based cohort study of 245,526 singleton term pregnancies. Women were grouped in
      five categories of BMI and in three gestational weight gain categories; < 8 kg
      (low weight gain), 8-16 kg and >16 kg (high weight gain). Obstetric and neonatal
      outcomes were evaluated after adjustments for maternal age, parity, smoking, year
      of birth. RESULT: Obese women with low gestational weight gain had a decreased
      risk for the following outcomes (adjusted odds ratio; 95% confidence interval):
      preeclampsia (0.52; 0.42-0.62), cesarean section (0.81; 0.73-0.90), instrumental
      delivery (0.75; 0.63-0.88), and LGA births (0.66; 0.59-0.75). There was a 2-fold
      increased risk for preeclampsia and LGA infants among average and overweight
      women with excessive weight gain. High gestational weight gain increased the risk
      for cesarean delivery in all maternal BMI classes. CONCLUSION: The effects of
      high or low gestational weight gain differ depending on maternal BMI and the
      outcome variable studied. Obese women may benefit from a low weight gain during
      pregnancy.

PMID- 16626717
TI  - Bladder tenderness as a physical sign for diagnosing cystitis in women.

PMID- 16626718
TI  - Drape estimation vs. visual assessment for estimating postpartum hemorrhage.
AB  - OBJECTIVE: To compare (1) visual estimation of postpartum blood loss with
      estimation using a specifically designed blood collection drape and (2) the drape
      estimate with a measurement of blood loss by photospectrometry. METHODS: A
      randomized controlled study was performed with 123 women delivered at the
      District Hospital, Belgaum, India. The women were randomized to visual or drape
      estimation of blood loss. A subsample of 10 drape estimates was compared with
      photospectrometry results. RESULTS: The visual estimate of blood loss was 33%
      less than the drape estimate. The interclass correlation of the drape estimate to
      photospectrometry measurement was 0.92. CONCLUSION: Drape estimation of blood
      loss is more accurate than visual estimation and may have particular utility in
      the developing world. Prompt detection of postpartum hemorrhage may reduce
      maternal morbidity and mortality in low-resource settings.

PMID- 16626720
TI  - ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic
      lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient
      mice.
AB  - The objective of the present study was to determine whether a novel acyl
      CoA:cholesterol acyltransferase (ACAT) inhibitor, pactimibe sulfate (CS-505),
      could reduce atherosclerotic lesions beyond and independent of the reduction
      achieved by cholesterol lowering alone from two different types of lesions. (1)
      Early lesion model. Twelve-week-old apolipoprotein E (apoE)(-/-) mice were
      treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3%
      cholestyramine for 12 weeks. Each treatment significantly reduced plasma
      cholesterol by a similar degree (43-48%). The antiatherosclerotic activity of
      0.1% CS-505, however, was more efficacious than the effects of the other
      treatments (90% versus 40-50%). (2) Advanced lesion model. Twenty-four-week-old
      apoE(-/-) mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12
      weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI
      1011 (77% versus 54%), whereas the plasma cholesterol-lowering effect of 0.1% CS
      505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical
      analysis demonstrated that CS-505 significantly reduced the number of macrophages
      and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data
      indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This
      antiatherosclerotic activity is exerted via both cholesterol lowering and direct
      ACAT inhibition in plaque macrophages.

PMID- 16626721
TI  - Helical flow as fluid dynamic signature for atherogenesis risk in aortocoronary
      bypass. A numeric study.
AB  - The main purpose of the study was to verify if helical flow, widely observed in
      several vessels, might be a signature of the blood dynamics of vein graft
      anastomosis. We investigated the existence of a relationship between helical flow
      structures and vascular wall indexes of atherogenesis in aortocoronary bypass
      models with different geometric features. In particular, we checked for the
      existence of a relationship between the degree of helical motion and the
      magnitude of oscillating shear stress in conventional hand-sewn proximal
      anastomosis. The study is based on the numerical evaluation of four bypass
      geometries that are attached to a simplified computer representation of the
      ascending aorta with different angulations relative to aortic outflow. The finite
      volume technique was used to simulate realistic graft fluid dynamics, including
      aortic compliance and proper aortic and graft flow rates. A quantitative method
      was applied to evaluate the level of helicity in the flow field associated with
      the four bypass models under investigation. A linear inverse relationship (R = 
      0.97) was found between the oscillating shear index and the helical flow index
      for the models under investigation. The results obtained support the hypothesis
      that an arrangement of the flow field in helical patterns may elicit damping in
      wall shear stress temporal gradients at the proximal graft. Accordingly, helical
      flow might play a significant role in preventing plaque deposition or in tuning
      the mechanotransduction pathways of cells. Therefore, results confirm that
      helical flow constitutes an important flow signature in vessels, and its strength
      as a fluid dynamic index (for instance in combination with magnetic resonance
      imaging flow visualization techniques) for risk stratification, in the activation
      of both mechanical and biological pathways leading to fibrointimal hyperplasia.

PMID- 16626722
TI  - Synthesis of UV-absorbing and fluorescent carrier ampholyte mixtures and their
      application for the determination of the operational pH values of buffering
      membranes used in isoelectric trapping separations.
AB  - Success in isoelectric trapping separations critically depends on the knowledge
      of the accurate operational pH value of the buffering membranes used. Currently,
      due to a lack of easy, rapid, accurate methods that can be used for the post
      synthesis determination of the operational pH value of a buffering membrane, only
      nominal pH values calculated from the amounts of the reagents used in the
      synthesis of the membranes and their acid-base dissociation constants are
      available. To rectify this problem, UV-absorbing and fluorescent carrier
      ampholyte mixtures were prepared by alkylating pentaethylenehexamine with a
      chromophore and a fluorophore, followed by Michael addition of acrylic acid and
      itaconic acid to the resulting oligoamine. Carrier ampholyte mixtures, with
      evenly distributed absorbance values across the 3<pI<10 range, were prepared by
      blending. The master blend served as the feed mixture in binary isoelectric
      trapping separations that used the buffering membrane to be characterized. The pI
      value of the most basic UV-absorbing or fluorescent carrier ampholyte collected
      in the anodic separation compartment, determined by full-column imaging capillary
      isoelectric focusing analysis, indicates the operational pH value of the
      separation membrane.

PMID- 16626723
TI  - Application of liquid-phase microextraction and on-column derivatization combined
      with gas chromatography-mass spectrometry to the determination of carbamate
      pesticides.
AB  - A method has been established for the determination of five carbamate pesticides
      in water samples using liquid-phase microextraction (LPME) followed by on-column
      derivatization and gas chromatography-mass spectrometric (GC-MS) determination.
      Trimethylphenylammonium hydroxide (TMPAH) and trimethylsulfonium hydroxide (TMSH)
      were used as derivatization reagent for extracts prior to GC-MS analysis as
      carbamate pesticides are thermally labile compounds. Parameters that affect the
      extraction efficiency (selection of organic solvent and extraction time) and
      derivatization efficiency (choice of derivatization reagent and concentration of
      derivatization reagent) were investigated. The proposed method provided good
      enrichment factors up to 224, with reproducibility ranging from 4.86 to 7.81%,
      and good linearity from 1 to 400 microg/L. The limits of detection (LODs) ranged
      between 0.2 and 0.8 microg/L (S/N = 3) using GC-MS with selective ion monitoring.
      This method was applied to the determination of carbamate pesticides in tap water
      and waste water.

PMID- 16626724
TI  - Adsorption of chromium ions from aqueous solution by using activated carbo
      aluminosilicate material from oil shale.
AB  - A novel activated carbo-aluminosilicate material was prepared from oil shale by
      chemical activation. The chemicals used in the activation process were 95 wt%
      sulfuric and 5 wt% nitric acids. The produced material combines the sorption
      properties and the mechanical strength of both activated carbon and zeolite. An X
      ray diffraction analysis shows the formation of zeolite Y, Na-X, and A-types,
      sodalite, sodium silicate, mullite, and cancrinite. FT-IR spectrum shows the
      presence of carboxylic, phenolic, and lactonic groups on the surface of this
      material. The zero point of charge estimated at different mass to solution ratio
      ranged from 7.9 to 8.3. Chromium removal by this material showed sorption
      capacity of 92 mg/g.

PMID- 16626725
TI  - Adsorption of Cu(II) and Ni(II) on solid humic acid from the Azraq area, Jordan.
AB  - Isotherms of adsorption of Cu(II) and Ni(II) onto solid Azraq humic acid (AZHA)
      were studied at different pH (2.0-3.7) values and 0.1 M NaClO4 ionic strength.
      The Langmuir monolayer adsorption capacity was found to range from 0.1 to 1.0
      mmol metal ion/g AZHA, where Cu(II) has higher adsorptivity than Ni(II). The
      previously reported NICA-Donnan parameters for sorption of Cu(II) on HA fit the
      amount of Cu(bound) determined in the present study at pH 3.7 but underestimates
      those at pH values of 3.0, 2.4, and 2.0. The contribution of low affinity sites
      to binding of metal ions increases with decreasing pH and increasing metal ion
      loading. The aggregation of HA, which is facilitated by decreasing pH and
      increasing metal loading, may increase the ability of low-affinity sites to
      encapsulate metal ions. The binding of Ni(II) to HA exhibits less heterogeneity
      and less multidentism than that of Cu(II). AZHA loaded with Cu(II) and Ni(II) was
      found to be insoluble in water with no measurable amount of desorbed metal ions.

PMID- 16626726
TI  - Reflectometric study of the adsorption of poly(vinyl imidazole) on a gold
      electrode, effects of pH, and applied potential.
AB  - The adsorption-desorption behavior of poly(vinyl imidazole), a weak polybase (pH
      dependent positive charge), on a gold electrode was investigated using optical
      fixed-angle reflectometry. Using an instrument comprising an impinging-jet
      system, the hydrodynamic conditions were well defined, making it possible to
      study the adsorption rate. Comparison between the actual adsorption rate and that
      of a purely diffusion-controlled process revealed the occurrence and the change
      of an electrostatic barrier in the adsorption process. The surface charge of the
      gold electrode was varied by means of an externally applied potential. The
      surface charge density was evaluated by separate electrochemical impedance
      spectroscopy. The uptake and the adsorption rate were very sensitive to pH and
      electrode polarization. At pH 3, the adsorption of the fully charged polymer
      increased fairly regularly with cathodic polarization, whereas it remained at
      about 0.4 mg m(-2) in the anodic zone At pH 8, the adsorption of the uncharged
      polymer decreased with the negative charge of the electrode due to the more
      favorable adsorption of potassium ions on the charged electrode. Discrepancies in
      adsorption-desorption measurements taken while cycling the pH were due to an
      electrostatic adsorption barrier.

PMID- 16626727
TI  - On the viscosity of composite suspensions of aluminum and ammonium perchlorate
      particles dispersed in hydroxyl terminated polybutadiene--New empirical model.
AB  - The rheological properties of fuel suspensions with various solid loadings up to
      close their maximum packing fraction and suspending media having different
      viscosities are investigated using the rotational viscometer at relatively low
      shear rates in which suspensions behave as Newtonian fluids. Aluminum (Al) and
      ammonium perchlorate (AP) particles are major solid components of any solid fuel
      system which should be distributed uniformly inside a polymeric binder based on
      hydroxyl terminated polybutadiene (HTPB). The experimental data generated in this
      investigation indicates that the relative viscosity of the suspensions is
      independent of viscosity of polymer binder, but in addition to solid content,
      geometrical aspects of the solid particles affect strongly the relative viscosity
      of suspensions. Maximum packing fraction of filler is found to be suitable
      quantitative measure of filler characteristics such as size, size distribution,
      shape and structure. Consequently, it is revealed that the relative viscosity of
      fuel suspension is a unique function of reduced volume fraction (Phi). Based on
      analogy of viscosity enhancement of reactive resin with cure conversion and
      suspension with filler content, an empirical model with two adjustable parameters
      originated from resin gelation model is suggested. According to this model and
      experimental results obtained in this investigation, a generalized model is
      proposed to describe the relative viscosity as a function of solid content in
      which the adjustable parameters are found to be general constants. The
      generalized model which is expressed as mu(r) = (1-Phi)(0.3 Phi-2) is found to be
      quite accurate to predict the experimental data. Furthermore, the applicability
      and accuracy of the generalized model are evaluated using the viscosity data of
      some suspension systems reported in the literature.

PMID- 16626728
TI  - Patterning in rapidly evaporated polymer solutions: formation of annular
      structures under evaporation of the poor solvent.
AB  - Patterning in the intensively evaporated polymer solutions based on polystyrene
      and poor solvent (acetone) was investigated. SEM and AFM studies demonstrated
      that annular elements of the surface topography are formed in this case, in
      contrast to the honeycomb patterns obtained under the evaporation of the good
      solvent (chloroform). The authors suggest that the theory of viscous dewetting
      developed by de Gennes explains the phenomenon satisfactorily.

PMID- 16626729
TI  - Geopolymeric adsorbents from fly ash for dye removal from aqueous solution.
AB  - Adsorbents from coal fly ash treated by a solid-state fusion method using NaOH
      were prepared. It was found that amorphous aluminosilicate geopolymers would be
      formed. These fly ash-derived inorganic polymers were assessed as potential
      adsorbents for removal of some basic dyes, methylene blue and crystal violet,
      from aqueous solution. It was found that the adsorption capacity of the
      synthesised adsorbents depends on the preparation conditions such as NaOH:fly-ash
      ratio and fusion temperature with the optimal conditions being at 1.2:1 weight
      ratio of Na:fly-ash at 250-350 degrees C. The synthesised materials exhibit much
      higher adsorption capacity than fly ash itself and natural zeolite. The
      adsorption isotherm can be fitted by Langmuir and Freundlich models while the two
      site Langmuir model producing the best results. It was also found that the fly
      ash derived geopolymeric adsorbents show higher adsorption capacity for crystal
      violet than methylene blue and the adsorption temperature influences the
      adsorption capacity. Kinetic studies show that the adsorption process follows the
      pseudo second-order kinetics.

PMID- 16626730
TI  - Facile fabrication of poly(p-phenylene ethynylene)/colloidal silica composite for
      nucleic acid detection.
AB  - Fabrication, characterization, and application of poly(phenylene ethynylene)
      (PPE)/silica composite particles are described. PPE is a class of conjugated
      polymers, which has been used for various sensory materials. However, its
      hydrophobic nature makes its application difficult in the aqueous phase,
      especially for biological substance detection. In this report, we utilized non
      aqueous soluble PPE, 15 nm of colloidal silica particles, and aminosilane to
      fabricate a biosensory platform. The resulting composite showed high aqueous
      compatibility, large surface area, high quantum efficiency, and versatile
      chemical modification including oligonucleotide coupling. By monitoring the
      fluorescence quenching of PPE, we could detect a quencher-labeled target
      oligonucleotide specifically. Stern-Volmer (SV) analysis showed different
      accessibility of fluorophores (PPE) to a quencher labeled target oligonucleotide.
      The accessibility of fluorophores and SV constant are determined to be 0.54 and
      4.2 x 10(7)M(-1), respectively, from a modified SV plot. This method will broaden
      the capability of conjugated polymers for the sensitive detection of biological
      substances.

PMID- 16626731
TI  - Centrifugation enhances integrin-mediated transduction of dendritic cells by
      conventional and RGD-modified adenoviral vectors.
AB  - The level of antigen loading can impact on the capacity for dendritic cells (DC)
      to activate T cell responses. Several different approaches to adenoviral (Ad)
      based transduction were therefore assessed for their effect on both transgene
      expression and T cell activation. While a conventional E1(-)/E3Delta Ad vector
      (Ad/GFP) produced a concentration-dependent expression of GFP, a modified vector
      expressing Arginine-Glycine-Aspartic Acid (RGD) sequence on its fiber knob (Ad
      RGD/GFP) enhanced transgene expression by 9-20-fold at each MOI. The addition of
      centrifugal force (2000xg) during DC transduction with Ad/GFP also increased
      expression up to 20-fold. However, combining centrifugation with the Ad-RGD/GFP
      vector produced no effect on transduction rate and only a 1.5- to 2-fold increase
      in GFP expression, suggesting overlapping mechanisms of action. Consistent with
      this, exogenous RGD peptide blocked transduction regardless of the vector used,
      or the addition of centrifugal force, and transduction was primarily limited to
      DC expressing the CD51 integrin receptor. Ad vectors expressing ovalbumin (OVA)
      were used to assess transduced DC for their capacity to activate OVA-specific T
      cells. We observed a significant relationship between transgene expression and
      the capacity for T cell activation regardless of whether transgene expression was
      increased by using a higher MOI, an RGD-modified vector, or by employing
      centrifugal force. Furthermore, combining these approaches produced synergistic
      effects on T cell activation. We conclude that RGD-modified vectors and
      centrifugation both enhance DC transduction by increasing entry via integrin
      receptors and that the capacity for T cell activation can be optimized by
      combining approaches to achieve the highest possible level of transgene
      expression.

PMID- 16626732
TI  - Structure and expressions of two circadian clock genes, period and timeless in
      the commercial silkmoth, Bombyx mori.
AB  - We cloned two circadian clock genes period (Bmper) and timeless (Bmtim) from the
      commercial silkmoth, Bombyx mori. Sequence analysis revealed a high degree of
      conservation among insects for both genes. BmPER predicted from the DNA sequence
      is a polypeptide of 1, 113 amino acids with functional domains such as PAS, PAC,
      nuclear localization signal (NLS) and cytoplasmic localization domain (CLD).
      Deduced BmTIM consists of 997 amino acids with PER interaction site (PIS) as well
      as NLS and CLD. Southern blot analyses revealed that Bmper and Bmtim are single
      copy genes. Northern blot analysis demonstrated that Bmper and Bmtim are
      expressed both in the head and peripheral tissues. We also examined temporal
      profiles of Bmper and Bmtim expressions in the head, flight muscle, testis and
      antenna of adult males under LD12:12 and LD16:8 by Real-Time PCR assays. Our data
      show that photoperiod differentially affects the temporal expression patterns of
      Bmper and Bmtim. The mRNA expression of Bmper and Bmtim in the head had a phase
      lead under LD12:12 compared to that under LD16:8, whereas photoperiod did not
      affect expression patterns in peripheral tissues relative to light-on.
      Photoperiod affected not only the phase relationship but also the expression
      level. In the testis and antenna, the level of transcription of Bmtim was low in
      LD12:12 but high in LD16:8. The daily differences in amplitudes of the Bmper and
      Bmtim expression rhythms were 2-fold in the head and 1.5-2.5 folds in the
      peripheral tissues examined.

PMID- 16626733
TI  - The CH-domain of calponin does not determine the modes of calponin binding to F
      actin.
AB  - Many actin-binding proteins have been observed to have a modular architecture.
      One of the most abundant modules is the calponin-homology (CH) domain, found as
      tandem repeats in proteins that cross-link actin filaments (such as fimbrin,
      spectrin and alpha-actinin) or link the actin cytoskeleton to intermediate
      filaments (such as plectin). In proteins such as the eponymous calponin, IQGAP1,
      and Scp1, a single CH-domain exists, but there has been some controversy over
      whether this domain binds to actin filaments. A previous three-dimensional
      reconstruction of the calponin-F-actin complex has led to the conclusion that the
      visualized portion of calponin bound to actin belongs to its amino-terminal
      homology (CH) domain. We show, using a calponin fragment lacking the CH-domain,
      that this domain is not bound to F-actin, and cannot be positioning calponin on F
      actin as hypothesized. Further, using classification methods, we show a
      multiplicity in cooperative modes of binding of calponin to F-actin, similar to
      what has been observed for other actin-binding proteins such as tropomyosin and
      cofilin. Our results suggest that the form and function of the structurally
      conserved CH-domain found in many other actin-binding proteins have diverged.
      This has broad implications for inferring function from the presence of
      structurally conserved domains.

PMID- 16626734
TI  - The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked cone
      dystrophies.
AB  - Absorption of light by visual pigments initiates the phototransduction pathway
      that results in degradation of the intracellular pool of cyclic-GMP (cGMP). This
      hydrolysis promotes the closing of cGMP-gated cation channels and consequent
      hyperpolarization of rod and cone photoreceptor cell membranes. Guanylate cyclase
      activating proteins (GCAPs) are a family of proteins that regulate retinal
      guanylate cyclase (GC) activity in a Ca2+-dependent manner. At high [Ca2+],
      typical of the dark-adapted state (approximately 500 nM), GCAPs inhibit retinal
      GCs. At the low [Ca2+] (approximately 50 nM) that occurs after the closing of
      cGMP-gated channels, GCAPs activate retinal GCs to replenish dark-state cGMP
      levels. Here, we report the crystal structure of unmyristoylated human GCAP3 with
      Ca2+ bound. GCAP3 is an EF-hand Ca2+-binding protein with Ca2+ bound to EF2, 3
      and 4, while Ca2+ binding to EF-hand 1 is disabled. GCAP3 contains two domains
      with the EF-hand motifs arranged in a tandem array similar to GCAP2 and members
      of the recoverin subfamily of Ca2+-binding proteins. Residues not involved in
      Ca2+ binding, but conserved in all GCAPs, cluster around EF1 in the N-terminal
      domain and may represent the interface with GCs. Five point mutations in the
      closely related GCAP1 have been linked to the etiology of cone dystrophies. These
      residues are conserved in GCAP3 and the structure suggests important roles for
      these amino acids. We present a homology model of GCAP1 based on GCAP3 that
      offers insight into the molecular mechanism underlying the autosomal dominant
      cone dystrophies produced by GCAP1 mutations.

PMID- 16626735
TI  - Viscous drag as the source of active site perturbation during protease
      translocation: insights into how inhibitory processes are controlled by serpin
      metastability.
AB  - The native form of serine protease inhibitors (serpins) is kinetically trapped in
      a metastable state, which is thought to play a central role in the inhibitory
      mechanism. The initial binding complex between a serpin and a target protease
      undergoes a conformational change that forces the protease to translocate toward
      the opposite pole. Although structural determination of the final stable complex
      revealed a detailed mechanism of keeping the bound protease in an inactive
      conformation, it has remained unknown how the serpin exquisitely translocates a
      target protease with an acyl-linkage unhydrolyzed. We previously suggested that
      the acyl-linkage hydrolysis is strongly suppressed by active site perturbation
      during the protease translocation. Here, we address what induces the transient
      perturbation and how the serpin metastability contributes to the perturbation.
      Inhibitory activity of alpha1-antitrypsin (alpha1AT) toward elastase showed
      negative correlations with medium viscosity and Stokes radius of elastase moiety,
      indicating that viscous drag directly affects the protease translocation. Stopped
      flow measurements revealed that the change in the inhibitory activity is
      primarily caused by the change in the translocation rate. The native stability of
      alpha1AT cavity mutants showed a negative correlation with the translocation rate
      but a positive correlation with the acyl-linkage hydrolysis rate, suggesting that
      the two kinetic steps are not independent but closely related. The degree of
      active site perturbation was probed by amino acid nucleophiles, supporting the
      view that the changes in the acyl-linkage hydrolysis rate are due to different
      perturbation states. These results suggest that the active site perturbation is
      caused by local imbalance between a pulling force driving protease translocation
      and a counteracting viscous drag force. The structural architecture of serpin
      metastability seems to be designed to ensure the active site perturbation by
      providing a sufficient pulling force, so the undesirable hydrolytic activity of
      protease is strongly suppressed during the translocation.

PMID- 16626736
TI  - Counterion charge density determines the position and plasticity of RNA folding
      transition states.
AB  - The self-assembly of RNA structure depends on the interactions of counterions
      with the RNA and with each other. Comparison of various polyamines showed that
      the tertiary structure of the Tetrahymena ribozyme is more stable when the
      counterions are small and highly charged. By monitoring the folding kinetics of
      the ribozyme as a function of polyamine concentration, we now find that the
      charge density of the counterions determines the positions of the folding
      transition states. The transition state ensemble (TSE) between U and N moves away
      from the native state as the counterion valence and charge density increase, as
      predicted by the Hammond postulate. The TSE is broader and less structured when
      the RNA is refolded in polyamines rather than Mg2+. That the charge density of
      the counterions determines the plasticity of the TSE demonstrates the importance
      of interactions among condensed counterions for the self-assembly of RNA
      structures. We propose that the major barrier to RNA folding is dominated by
      entropy changes when counterion charge density is low and enthalpy differences
      when it is high.

PMID- 16626737
TI  - Unique regulation of the active site of the serine esterase S-formylglutathione
      hydrolase.
AB  - S-Formylglutathione hydrolases (SFGHs) are highly conserved thioesterases present
      in prokaryotes and eukaryotes, and form part of the formaldehyde detoxification
      pathway, as well as functioning as xenobiotic-hydrolysing carboxyesterases. As
      defined by their sensitivity to covalent modification, SFGHs behave as cysteine
      hydrolases, being inactivated by thiol alkylating agents, while being insensitive
      to inhibition by organophosphates such as paraoxon. As such, the enzyme has been
      classified as an esterase D in animals, plants and microbes. While SFGHs do
      contain a conserved cysteine residue that has been implicated in catalysis,
      sequence analysis also reveals the classic catalytic triad of a serine hydrolase.
      Using a combination of selective protein modification and X-ray crystallography,
      AtSFGH from Arabidopsis thaliana has been shown to be a serine hydrolase rather
      than a cysteine hydrolase. Uniquely, the conserved reactive cysteine (Cys59)
      previously implicated in catalysis lies in close proximity to the serine
      hydrolase triad, serving a gate-keeping function in comprehensively regulating
      access to the active site. Thus, any covalent modification of Cys59 inhibited all
      hydrolase activities of the enzyme. When isolated from Escherichia coli, a major
      proportion of recombinant AtSFGH was recovered with the Cys59 forming a mixed
      disulfide with glutathione. Reversible disulfide formation with glutathione could
      be demonstrated to regulate hydrolase activity in vitro. The importance of Cys59
      in regulating AtSFGH in planta was demonstrated in transient expression assays in
      Arabidopsis protoplasts. As determined by fluorescence microscopy, the Cys59Ser
      mutant enzyme was shown to rapidly hydrolyse 4-methylumbelliferyl acetate in
      paraoxon-treated cells, while the native enzyme was found to be inactive. Our
      results clarify the classification of AtSFGHs as hydrolases and suggest that the
      regulatory and conserved cysteine provides an unusual redox-sensitive regulation
      to an enzyme functioning in both primary and xenobiotic metabolism in prokaryotes
      and eukaryotes.

PMID- 16626738
TI  - Crystal structure of SUMO-3-modified thymine-DNA glycosylase.
AB  - Modification of cellular proteins by the small ubiquitin-like modifier SUMO is
      important in regulating various cellular events. Many different nuclear proteins
      are targeted by SUMO, and the functional consequences of this modification are
      diverse. For most proteins, however, the functional and structural consequences
      of modification by specific SUMO isomers are unclear. Conjugation of SUMO to
      thymine-DNA glycosylase (TDG) induces the dissociation of TDG from its product
      DNA. Structure determination of the TDG central region conjugated to SUMO-1
      previously suggested a mechanism in which the SUMOylation-induced conformational
      change in the C-terminal region of TDG releases TDG from tight binding to its
      product DNA. Here, we have determined the crystal structure of the central region
      of TDG conjugated to SUMO-3. The overall structure of SUMO-3-conjugated TDG is
      similar to the previously reported structure of TDG conjugated to SUMO-1, despite
      the relatively low level of amino acid sequence similarity between SUMO-3 and
      SUMO-1. The two structures revealed that the sequence of TDG that resembles the
      SUMO-binding motif (SBM) can form an intermolecular beta-sheet with either SUMO-1
      or SUMO-3. Structural comparison with the canonical SBM shows that this SBM-like
      sequence of TDG retains all of the characteristic interactions of the SBM,
      indicating sequence diversity in the SBM.

PMID- 16626739
TI  - Structural bioinformatics prediction of membrane-binding proteins.
AB  - Membrane-binding peripheral proteins play important roles in many biological
      processes, including cell signaling and membrane trafficking. Unlike integral
      membrane proteins, these proteins bind the membrane mostly in a reversible
      manner. Since peripheral proteins do not have canonical transmembrane segments,
      it is difficult to identify them from their amino acid sequences. As a first step
      toward genome-scale identification of membrane-binding peripheral proteins, we
      built a kernel-based machine learning protocol. Key features of known membrane
      binding proteins, including electrostatic properties and amino acid composition,
      were calculated from their amino acid sequences and tertiary structures, which
      were then incorporated into the support vector machine to perform the
      classification. A data set of 40 membrane-binding proteins and 230 non-membrane
      binding proteins was used to construct and validate the protocol. Cross
      validation and holdout evaluation of the protocol showed that the accuracy of the
      prediction reached up to 93.7% and 91.6%, respectively. The protocol was applied
      to the prediction of membrane-binding properties of four C2 domains from novel
      protein kinases C. Although these C2 domains have 50% sequence identity, only one
      of them was predicted to bind the membrane, which was verified experimentally
      with surface plasmon resonance analysis. These results suggest that our protocol
      can be used for predicting membrane-binding properties of a wide variety of
      modular domains and may be further extended to genome-scale identification of
      membrane-binding peripheral proteins.

PMID- 16626740
TI  - Aminoglycoside resistance by ArmA-mediated ribosomal 16S methylation in human
      bacterial pathogens.
AB  - Aminoglycosides are a medically important class of antibiotics used to treat
      serious infections. Methylation of the ribosomal target is an emerging mechanism
      that produces a high level of resistance to all clinically available
      aminoglycosides for systemic therapy except streptomycin. ArmA was the first
      methyltransferase using this mechanism to be discovered in a clinical isolate. We
      demonstrate that ArmA methylates the N7 position of nucleotide G1405 in 16S rRNA.
      Methylation at this position is presumed to mediate cellular resistance by
      blocking aminoglycoside binding by ribosomes. To test this hypothesis, we
      measured the binding of gentamicin by 30S subunits. Under our conditions, we did
      not observe binding by ribosomes methylated by ArmA. Furthermore, the ArmA
      methylation reaction is specific for the 30S ribosomal subunit; neither 16S rRNA
      alone nor the 70S ribosome is a substrate for this reaction under our
      experimental conditions, implicating ribosomal proteins in substrate recognition.
      The biochemical characteristics of ArmA place it in the Agr family of
      methyltransferases, whose members are predominantly anti-suicide genes from
      Actinomycetes aminoglycoside producers. The discrepancy between the 30% GC
      content of armA and the >60% GC content of Actinomycetes, however, calls into
      question the origin of armA. We demonstrate that surprisingly, the natural
      promoter of armA from gram-negative Klebsiella pneumoniae was active in gram
      positive Bacillus subtilis, suggesting that armA originated from a low-GC, gram
      positive aminoglycoside-producing organism.

PMID- 16626741
TI  - Increased cerebellar vermis white-matter volume in men with schizophrenia.
AB  - We aimed to investigate cerebellar structural abnormalities and their functional
      significance in patients with schizophrenia. Forty right-handed men with
      schizophrenia and 40 sex, age and handedness matched controls underwent a
      volumetric magnetic resonance scan with 1 mm3 isotropic spatial resolution.
      Cerebellar grey- and white-matter volumes were analysed using voxel-based
      morphometry. Patients with schizophrenia completed a battery of
      neuropsychological tests assessing sustained attention (continuous performance
      test), memory (Hopkins memory test) and executive function (verbal fluency and
      Wisconsin card sorting tests). Patients with schizophrenia exhibited
      significantly increased cerebellar vermis white-matter volume compared with
      controls. By contrast, total cerebellar volume, and grey- and white-matter
      volumes of cerebellar hemispheres were not significantly different between
      groups. Increased vermis white-matter volume in patients was associated with poor
      verbal fluency performance. We concluded that increased white-matter in the
      cerebellar vermis, possibly suggesting anomalous connectivity, may be associated
      with verbal executive dysfunction in men with chronic schizophrenia.

PMID- 16626742
TI  - Vigilance monitoring for operator safety: A simulation study on highway driving.
AB  - INTRODUCTION: Alertness of individuals operating vehicles, aircrafts, and
      machinery is a pre-requisite for safety of the individual and for avoiding
      economic losses. In this paper, we present a new technique for determining the
      alertness level of the operator and elaborate the methodology for the specific
      case of highway driving METHOD: Our hypothesis is that the time derivative of
      force exerted by the driver at the vehicle-human interfaces can be used to
      construct a signature of individual driving styles and to discern different
      levels of alertness RESULTS: In this study, we present experimental results
      corroborating this hypothesis and introduce a parameter, 'spikiness index,' for
      the time series data of the force derivative to quantify driver alertness IMPACT
      ON INDUSTRY: The low cost, ruggedness, and low-volume data processing
      requirements of the proposed technique give it a competitive edge over existing
      predominantly image processing based vigilance monitoring systems.

PMID- 16626743
TI  - Clinical characteristics of cortical multiple sclerosis.
AB  - There are several articles in this special issue in which authors eloquently
      describe neurobehavioural and cognitive complications of multiple sclerosis with
      relevant neuropsychological assessments and neuroimaging findings. However
      behavioural and cognitive presentation of multiple sclerosis remains poorly
      understood. Two years ago, we reported a series of patients with multiple
      sclerosis who presented with neurobehavioural symptoms and had neuropsychological
      deficits consistent with cortical dysfunction. Based on previous case reports,
      pathological studies of cerebral cortex in multiple sclerosis and advanced
      neuroimaging studies we suggested that neurobehavioural presentation of multiple
      sclerosis represents a new variant called "cortical multiple sclerosis". The
      condition is characterised by predominant or exclusive cortical pathology
      presenting with neurobehavioural symptoms, such as depression, amnesia or
      distinct cortical syndromes. Since the publication of our report, there has been
      further neuroimaging and neuropathological findings that further supported the
      above concept. In addition, observation of more patients with this condition
      helped us to formulate a logical approach in the detection of these patients.
      This article focuses on their clinical characteristics.

PMID- 16626744
TI  - Retraining attention in MS.
AB  - Cognitive decline is frequently observed in multiple sclerosis (MS) and has a
      major impact on quality of life. Therefore it would be important to offer
      therapeutic strategies to the patients. In the past, several studies were
      conducted on pharmacological or cognitive treatment. However, there is currently
      no specific treatment for cognitive decline and the studies published so far
      report heterogeneous results. The present paper focuses on the cognitive
      treatment strategies by reviewing and discussing the few studies that have been
      carried out in this area. In addition, results of a recently completed fMRI study
      on the visualization of cognitive training effects will be reported. This review
      clearly points out that further research in this area is needed to clarify the
      effects of cognitive intervention. Larger sample sizes and standardized
      neuropsychological outcome measures as well as standardized training tools are
      required to allow for comparisons between different studies and to improve our
      understanding of cognitive decline and the processes of cognitive recovery in MS.

PMID- 16626745
TI  - Should neurologists measure fibrinogen concentrations?

PMID- 16626746
TI  - Cognitive dysfunction and emotional-behavioural changes in MS: the potential of
      positron emission tomography.
AB  - Cognitive dysfunction and emotional-behavioral changes are symptoms with
      increasing clinical relevance during progression of the disease. They cannot be
      explained by demyelination of white matter alone but clearly indicate cortical
      dysfunction. Positron emission tomography (PET) provides methods to assess
      cortical dysfunction quantitatively by measuring cerebral glucose metabolism
      using the tracer (18)F-2-fluoro-2-deoxy-d-glucose (FDG). The technique has been
      employed to study fatigue and disease progression. Microglial activation was
      studied by 11C-PK-11195 PET. It was found not only in active plaques but also in
      degenerating fibre tracks. Other tracers offer a broad spectrum of measuring
      local physiological functions and pathophysiological processes, but some of them
      are still limited to experimental animal research.

PMID- 16626747
TI  - Measures of cognitive and emotional changes in multiple sclerosis and underlying
      models of brain dysfunction.
AB  - In this short critical review, I will take first into account the cognitive
      defects usually observed in multiple sclerosis (MS) patients, the
      neuropsychological batteries constructed to measure these defects and the main
      objections that can be addressed to these batteries. I will then pass to consider
      the problem of the model of brain dysfunction corresponding to the pattern of
      neuropsychological impairment typical of MS patients, stressing the main
      differences between anatomical progression and across subjects consistency of the
      cognitive defects observed in Alzheimer's disease and MS patients. In the last
      part of my review, I will shortly consider the issues of the emotional changes
      observed in MS patients, of the interpretation of these emotional disorders and
      of the scales used to measure them.

PMID- 16626748
TI  - MRI markers of destructive pathology in multiple sclerosis-related cognitive
      dysfunction.
AB  - Studies with conventional magnetic resonance imaging (MRI) indicate that
      cognitive impairment in multiple sclerosis (MS) patients is not fully explained
      by the burden of T2-visible lesions in the brain. Other non-conventional MRI
      techniques with increased specificity to the more destructive aspects of MS
      pathology, such as magnetization transfer MRI, diffusion-weighted MRI and proton
      magnetic resonance spectroscopy, have recently been applied to MS cognitive
      studies. The results suggest that the presence and extent of "occult" MS
      pathological features in the normal-appearing brain tissue and the location of
      lesions in eloquent sites play a central role in the pathogenesis of MS
      neuropsychological impairment.

PMID- 16626749
TI  - Peripheral myelin protein 22 is expressed in human central nervous system.
AB  - We studied the expression of peripheral myelin protein 22 (PMP22) gene in the
      human central nervous system (CNS). Northern blot analysis was performed with
      polyA+ RNA blots containing several parts of the human brain and the spinal cord
      using human PMP22 cDNA as a probe. As two alternative PMP22 transcripts have been
      reported and since exon 1A-containing transcripts are associated with myelin
      formation, the exon 1A fragment was also used to examine this transcript. Total
      PMP22 mRNA was significantly detected in most parts of brain and spinal cord,
      while exon 1A-containing transcripts were detected in the medulla, spinal cord
      and corpus callosum. PMP22-like immunoreactivity was identified in motor neurons
      and preganglionic sympathetic neurons in the spinal cord. PMP22 was also detected
      in pia mater of the spinal cord. These results suggest that PMP22 might play an
      important role in human CNS.

PMID- 16626750
TI  - Cognitive fatigue in multiple sclerosis: findings from a two-wave screening
      project.
AB  - BACKGROUND: Multiple sclerosis (MS) patients commonly suffer from fatigue and
      define it as one of their most disabling symptom profoundly disrupting their
      lives. However, the relationship of fatigue to cognitive functions and its impact
      on quality of life have not been widely studied. AIM: To define (1) "cognitive
      fatigue", (2) survey its frequency and (3) characterize severity and impact on
      quality of life in MS patients in the first 10 years of the disease. METHODS: A
      two-wave design was utilized to enrich the studied population in subjects whose
      fatigue is significant. In the first wave, fatigue was measured by the self
      reported fatigue severity scale (FSS) in randomly selected MS patients from our
      computerized database. Patients responding to the 9th item of the FSS i.e.,
      "Fatigue interferes with my work, family, or social life" by a grade of 3 or
      higher (of 7) were further assessed (wave two) by the fatigue impact scale (FIS)
      and the RAYS quality of life questionnaire. RESULTS: Of the 259 patients that
      completed the first-wave screening, 158 patients (61%, 118 females, mean age
      41.1+/-9.2 years, mean disease duration 6.2+/-5.5 years) satisfied the additional
      criterion and were defined to suffer from significant fatigue. The great majority
      of these patients-91.7%-had a relapsing-remitting disease course, mean FIS score
      was 77+/-25.9 and their mean EDSS was 2.9+/-2.6. Fatigue was reported to occur
      most of the day in 30.9% of patients, persist in 69% for more than 1 year, and in
      59.8%, it was reported not to be associated with effort. No correlations were
      found between age, gender, disease duration or neurological disability and FIS
      cognitive subscale score. Significant correlations were found between the FIS
      cognitive subscale score and the three domains (physical, psychological and
      social-familial) of the RAYS quality of life questionnaire (p<0.001).
      CONCLUSIONS: Cognitive fatigue was found in more than half of MS patients in the
      first decade from onset that were particularly selected for significant fatigue
      in their lives. This aspect of fatigue correlated with all quality of life
      domains and especially with psychological everyday tasks.

PMID- 16626751
TI  - Predicting neuropsychological abnormalities in multiple sclerosis.
AB  - Multiple Sclerosis (MS) is associated with MRI signal alteration and
      neuropsychological (NP) dysfunction. Screening tools have been developed to
      identify patients at high risk for these neurological complications of MS. One
      such measure, the Multiple Sclerosis Neuropsychological Screening Questionnaire
      (MSNQ), has well-established reliability and predictive validity. In this
      article, we report on the accumulated findings derived from 162 consecutive
      research participants and MS clinic attendees. Our data show significant
      correlation between both patient- and informant-report MSNQ and NP impairment. As
      shown previously, larger, and more significant correlations are found between
      informant-report MSNQs than with patient-report MSNQs. In addition, we find that
      the MSNQ predicts follow-up NP testing 51 weeks after baseline with a similar
      degree of association. Finally, the MSNQ is correlated with MRI measures of whole
      brain lesion burden and atrophy, secondary progressive course, and vocational
      disability. We conclude that the MSNQ is reliable and valid for detecting
      neuropsychological and neuropsychiatric complications of MS.

PMID- 16626752
TI  - Effects of donepezil on memory and cognition in multiple sclerosis.
AB  - Acetylcholinesterase inhibitors are used to treat dementia associated with
      Alzheimer's disease, but their cognitive benefits may extend to additional
      disorders such as multiple sclerosis (MS). A single-center double-blind placebo
      controlled randomized clinical trial evaluated the effectiveness of donepezil in
      a sample of 69 MS persons selected for initial memory difficulties. Subjects
      received neuropsychological assessment at baseline and after 24 weeks of
      treatment. The primary outcome was change in total recall on the Selective
      Reminding Test, a measure of verbal learning and memory. Secondary outcomes
      included other neuropsychological tests from the Brief Repeatable Battery,
      patient-reported change in memory, and physician-reported impression of cognitive
      change. Donepezil improved memory performance on the SRT compared to placebo.
      This benefit remained significant after controlling for various covariates
      including Expanded Disability Status Scale (EDSS), MS subtype, interferon beta
      use, treatment group beliefs, gender, baseline selected reminding test (SRT)
      score, and reading ability. Subjects on donepezil were more likely to report
      memory improvement (65.7%) than those on placebo (32.4%). The clinician also
      reported cognitive improvement in more donepezil (54.3%) than placebo (29.4%)
      subjects. No serious adverse events related to study medication occurred.
      However, more donepezil (34.3%) than placebo (8.8%) subjects reported
      unusual/abnormal dreams. Donepezil improved learning and memory in MS patients
      with initial cognitive difficulties in a single-center clinical trial.
      Replication of results in a larger multi-center investigation is warranted in
      order to more definitively assess the efficacy of this intervention.

PMID- 16626753
TI  - Brain reorganization during attention and memory tasks in multiple sclerosis:
      insights from functional MRI studies.
AB  - Deficits in memory and attention frequently occur during the course of multiple
      sclerosis (MS). In patients with MS the severity of cognitive manifestations is
      not closely related to indices of structural brain damage on both conventional
      and non conventional magnetic resonance imaging (MRI). It is conceivable that the
      ability of the brain to compensate for tissue impairment or loss may contribute
      to the maintenance of normal performance despite scattered brain lesions.
      Accordingly, using functional MRI (fMRI), patients with multiple sclerosis showed
      a greater extent of brain activation during motors tasks than controls. Changes
      in functional organization of the cerebral cortex have also been reported by fMRI
      studies comparing the activation patterns during cognitive tasks in patients with
      MS and in healthy subjects. Differences in patients' selection, activation
      paradigm, experimental design and MR acquisition parameters make, however, the
      results obtained from fMRI studies difficult to be compared and may explain, at
      least partially, some discrepant findings. Nevertheless, fMRI studies provide a
      new interesting way of understanding how the brain can change its functional
      organization in response to MS pathology, and might be useful in the study of the
      effects of either rehabilitation or pharmacological agents on brain plasticity.

PMID- 16626754
TI  - MRI of combination treatment of embolic stroke in rat with rtPA and atorvastatin.
AB  - To test the hypothesis that combination treatment of embolic stroke with rtPA and
      statins improves the efficacy of thrombolytic therapy in rats. Rats subjected to
      embolic MCA occlusion (MCAo) were randomized into control (n = 10) and treatment
      (n = 9) groups. Four hours after MCAo, a combination of rtPA and atorvastatin
      (treatment) or saline (control) was administered. MRI measurements were performed
      on all animals at 2 h, 24 h and 48 h after MCAo. The patency of cerebral
      microvessels was examined using fluorescent microscopy. MRI images showed
      complete blockage of the right MCA and a reduction of CBF in the territory
      supplied by the MCA 2 h after MCAo for all animals. By 48 h after stroke, MRI
      showed that the decreased lesion size, elevated CBF and increased incidence of
      recanalization were found in treated rats compared with the control rats. The
      combination treatment significantly increased microvascular patency (16.3 +/-
      5.5% vs. 12.4 +/- 3.5%, of field-of-view) and reduced the infarct volume (23.1 +/
      9.6% vs. 38.8 +/- 13.3%, of hemisphere). These data demonstrate that the co
      administration of rtPA and atorvastatin 4 h after ischemia is efficacious and is
      reflected by the MRI indices of recanalization of the MCA, reduction of secondary
      microvascular perfusion deficits and reduction of the ischemic lesion.

PMID- 16626755
TI  - Subcortical vascular cognitive impairment: similarities and differences with
      multiple sclerosis.
AB  - Subcortical vascular cognitive impairment is caused by lacunes and widespread
      ischemic white matter damage which closely resembles white matter abnormalities
      seen in multiple sclerosis. Recent evidence suggests that the progression rate of
      ischemic white matter lesions on MRI is very similar to that observed in multiple
      sclerosis. Consequently, it has been proposed to use MRI for monitoring disease
      activity not only in multiple sclerosis but also in vascular dementia trials.
      There is first evidence from magnetization transfer imaging studies that other
      than in MS normal appearing white matter is not affected in cerebral small vessel
      disease. This contrasts the hypothesis that ischemic white matter damage extends
      far beyond changes visible on conventional MR. The cognitive consequences of both
      diseases are strikingly similar which is at least partly caused by damage to
      frontal-subcortical circuits. Involvement of these common functional anatomical
      structures and their modulatory transmitter systems has now led to common
      interventional approaches such as the use of cholinesterase inhibitors.

PMID- 16626757
TI  - Interferons and cognition.
AB  - Cognitive impairment in multiple sclerosis is frequent, but the effect of
      immunomodulating drugs and mainly interferon beta (IFNbeta) on the
      neuropsychological aspects of the disease has not been fully studied. The data
      that we have are not conclusive. This paper reviews the effect of IFNbeta on
      cognition in the different clinical forms of the disease and the future
      directions of clinical trials.

PMID- 16626758
TI  - Neuropsychological assessment, quantitative MRI and ApoE gene polymorphisms in a
      series of MS patients treated with IFN beta-1b.
AB  - Few trials issued the effect of disease-modifying medications on cognitive
      functions in multiple sclerosis. We designed an open-label longitudinal study to
      evaluate, during 2 years, cognitive performance and its relationship with MRI
      data and ApoE polymorphism findings in a group of relapsing-remitting (RR)
      multiple sclerosis (MS) Interferon (IFN) beta-1b-treated patients (median age 30
      years, median disease duration 3.4 years). Complete neuropsychological battery
      was grouped into attention, information learning/memory, language and visuo
      spatial functions. Fifty-two patients (33 females) were enrolled in the study.
      Six patients (11.5%) dropped out, mainly due to side effects. At baseline
      neuropsychological evaluation, we found 54% normal, 42% mildly impaired and 4%
      moderately impaired patients. At 2 years follow-up, cognitive status was stable
      in 65%, improved in 33% and worsened in 2% of patients. No significant relations
      were found between global cognitive outcome vs. EDSS change, clinical disease
      activity, MRI data or ApoE gene polymorphisms over the 2 years follow-up. EDSS
      and MRI fractional volumes were found to correlate with the performance at single
      tests. Twenty-one patients (45.6%) showed active MRI scans throughout the study,
      without any worsening at the corresponding neuropsychological examination. This
      ongoing trial suggests a possible beneficial effect of IFN beta-1b treatment on
      cognitive functions in RRMS patients. Extension of follow-up and further data
      analyses are needed to confirm and clarify these findings.

PMID- 16626759
TI  - Modelling slow wave activity in the small intestine.
AB  - We have developed an anatomically based model to simulate slow wave activity in
      the small intestine. Geometric data for the human small intestine were obtained
      from the Visible Human project. These data were used to create a one-dimensional
      finite element mesh of the entire small intestine using an iterative fitting
      procedure. The electrically active components of the intestinal walls were
      modelled using a modified Fitzhugh-Nagumo cell model embedded within a
      longitudinal smooth muscle layer and a layer containing Interstitial Cells of
      Cajal. Within these layers, the monodomain equation was used to describe slow
      wave propagation. To solve the monodomain equation, a high-resolution finite
      difference grid, with an average spatial resolution of 0.95 mm, was embedded
      within each finite element. The resulting simulations of intestinal activity
      agree with the experimental observation that slow wave frequency gradually
      declines from 12 cycles per minute (cpm) in the duodenum to 8 cpm at the terminal
      ileum. Furthermore, the simulations demonstrated a decrease in conduction
      velocity with distance along the small intestine (10.7 cm/s in the duodenum,
      5.1cm/s in the jejunum and 1.4 cm/s in the ileum), matching experimental
      recordings from the canine small intestine. We conclude that the framework
      presented here is capable of qualitatively simulating normal slow wave activity
      in an anatomical model of the small intestine.

PMID- 16626760
TI  - Activation of alpha- and beta-estrogen receptors by persistent pesticides in
      reporter cell lines.
AB  - Many persistent pesticides have been implicated in reproductive and developmental
      adverse effects, in man and wildlife. It has been hypothesized that these so
      called xeno-hormones could upset the endocrine system function by binding to
      human estrogen receptor alpha and beta (ERalpha, beta) and thus be responsible
      for the higher incidence of breast and cervical cancer, infertility and
      endometriosis. In this report, forty-nine pesticides were tested for ERalpha and
      beta activation or inhibition in stable reporter cell lines, HELN ERalpha and
      ERbeta. Stable transfection of the ERalpha and ERbeta constructs together with an
      estrogen reporter luciferase vector into the HeLa cell line resulted in two
      estradiol-sensitive cell lines. In our model, fifteen of the tested pesticides
      were found to agonize the ERalpha-mediated transcription in a dose-dependent
      manner and DDT, trans-nonachlor, chlordane, fenvalerate and toxaphene were also
      capable to activate ERbeta. Antagonistic activities toward hERalpha and hERbeta
      were shown in three (carbaryl, pentachlorophenol and 2,4,5-trichlorophenoxyacetic
      acid) and seven (chlordecone, methoxychlor, carbaryl, endosulfan, endrin,
      dieldrin, aldrin) pesticides, respectively. Remarkably chlordecone and
      methoxychlor which were the most effective antagonist compounds for hERbeta, were
      agonists for hERalpha. Although the ERalpha activation potential of the
      pesticides was lower than that of estradiol, the overall body scale response
      might be amplified by the ability of pesticides to act via several mechanisms and
      by frequent and prolonged exposure to different pesticides, even at low
      concentrations.

PMID- 16626761
TI  - Effects of genistein on angiotensin-converting enzyme in rats.
AB  - Genistein (4,5,7-trihydroxyisoflavone), a phytoestrogen with selective estrogen
      receptor modulator properties, has received a great deal of attention over the
      last few years because of its potentially preventive roles against cardiovascular
      diseases. However, the precise molecular mechanisms for this modulation are not
      fully elucidated. In this study, we investigated (both in vivo and in vitro) the
      relationship between genistein and the changes of angiotensin-converting enzyme
      (ACE) in rat aortic endothelial cells (RAECs), serum and tissue (aorta). ACE
      expression was assessed by the immunofluorescence and the reverse transcriptase
      polymerase chain reaction (RT-PCR) assay. Serum and tissue ACE activity was
      detected with a commercial kit. Genistein exhibited a concentration-dependent
      inhibitory effect on the expression of ACE, particularly at higher concentrations
      (24.70+/-1.20 at 100microM, P<0.01, and 18.22+/-0.92 at 200microM, P<0.01
      compared with the control group 50.49+/-5.19). The estrogen receptor blocker
      tamoxifen at 100microM attenuated this effect of genistein. The extracellular
      signal-regulated kinase 1/2 (ERK1/2) blocker PD98059 also markedly inhibited this
      effect. The observations in vivo were highly consistent with the data in RAECs.
      These results indicate that genistein inhibits the expression of ACE via estrogen
      receptor and subsequently ERK1/2 signaling pathway in RAECs. Our results suggest
      that the down-regulation of ACE with a consequent change in the circulating
      levels of angiotensin II (Ang II), vasorelaxant angiotensin-(1-7) [Ang-(1-7)] and
      bradykinin plays an important role in cardiovascular effects of genistein through
      the ERK1/2 pathway.

PMID- 16626762
TI  - Y-40138, a multiple cytokine production modulator, protects against D
      galactosamine and lipopolysaccharide-induced hepatitis.
AB  - Acute and fulminant liver failure induced by viral hepatitis, alcohol or other
      hepatotoxic drugs are associated with tumor necrosis factor (TNF) production. D
      Galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver injury is an
      experimental model of fulminant hepatic failure. In this model, TNF-alpha plays a
      central role in the pathogenesis of D-GalN/LPS-induced liver injury in mice. Y
      40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl]
      acetamide.HCl inhibits TNF-alpha and augments interleukin (IL)-10 production in
      LPS-injected mice in plasma. In the present study, we examined the effect of Y
      40138 on D-GalN/LPS-induced hepatitis. Y-40138 (10mg/kg, i.v.) significantly
      suppressed TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) production
      and augmented IL-10 production in plasma. In addition, Y-40138 significantly
      inhibited TNF-alpha production induced by direct interaction between human T
      lymphocytes and macrophages. Y-40138 suppressed plasma alanine transaminase (ALT)
      elevation and improved survival rate in D-GalN/LPS-injected mice, and it is
      suggested that the protective effect of Y-40138 on hepatitis may be mediated by
      inhibition of TNF-alpha and MCP-1, and/or augmentation of IL-10. This compound is
      expected to be a new candidate for treatment of cytokine and/or chemokine-related
      liver diseases such as alcoholic hepatitis.

PMID- 16626763
TI  - Does altitudinal difference modulate the respiratory properties in subterranean
      rodents' (Cryptomys hottentotus mahali) blood?
AB  - Do burrowing mammals that naturally experience hypoxic and hypercapnic conditions
      exhibit modifications to the blood chemistry at high altitudes? We investigated
      two populations of the Lesotho mole-rat living at different altitudes in the
      highlands of the Drakensberg. There was no significant difference between the
      specimens from 3200 and 1600 m in mean red blood cell count (RCC=8.9x10(6)+/
      1.6x10(6) vs. 8.4x10(6)+/-0.95x10(6) mm3, respectively) or packed red cell
      volumes (haematocrit=0.51+/-0.06 vs. 0.49+/-0.05, respectively). However, blood
      haemoglobin (Hb) concentration was significantly higher in the high altitude than
      in the low-altitude specimens (178+/-9 vs. 160+/-16 g/l). The oxygen equilibrium
      curves of thawed whole blood showed no displacement to the left in the animals
      sampled at the higher elevation. The data indicate that the oxygen-transporting
      properties of mole-rat blood do not change markedly with increased elevation and
      that burrowing mammals are a priori hypoxia-adapted.

PMID- 16626764
TI  - Air hunger and ventilation in response to hypercapnia: effects of repetition and
      anxiety.
AB  - We investigated the effects of anxiety on the intensity of air hunger during
      gradually increasing levels of CO2 until the end-tidal fractional concentration
      of CO2 was 7.9% or air hunger was intolerable. Normal high and low (trait)
      anxious participants (N=23) went through three rebreathing trials (15 min
      interval). Breathing behaviour was continuously monitored and air hunger was
      rated every 12 s. The threshold for responding to the increased CO2 was always
      lower for the subjective rating than for the ventilatory response. Habituation
      across trials was observed for both the ventilatory response and the air hunger
      rating regardless of anxiety. However, beyond the threshold, the slope in air
      hunger ratings decreased across trials in low anxious persons and tended to
      increase in high anxious persons (interaction P<0.05). No differences occurred in
      the slopes of the breathing responses. The findings documented uncoupling of the
      physiological and subjective responses during CO2-induced air hunger.

PMID- 16626765
TI  - Nutrient-conditioned flavor preference and incentive value measured by
      progressive ratio licking in rats.
AB  - Rats develop strong preferences for flavors associated with the postingestive
      actions of glucose and other nutrients. This preference may involve changes in
      both the hedonic appeal and incentive salience of the nutrient-paired flavor. The
      present study used a progressive ratio (PR) operant licking task to evaluate the
      degree to which nutrient conditioning changes the incentive value of flavors.
      Food restricted rats were trained to associate one flavored saccharin solution
      (CS+) with intragastric glucose infusions and another flavored solution (CS-)
      with water infusions. The rats subsequently showed a strong preference for the
      CS+ in two-bottle tests and also licked more for the CS+ than CS- in PR tests. PR
      licking for the CS+ was similar to that for an 8% fructose solution. Together
      with earlier data indicating that the CS- is isopreferred to a 3% fructose
      solution, these findings indicate that IG glucose conditioning enhances the
      hedonic and incentive value of the CS+ solution so that the animal responds as if
      the solution had a sweeter taste.

PMID- 16626766
TI  - Occurrence and taxonomic significance of cysteine sulphoxides in the genus Allium
      L. (Alliaceae).
AB  - Methiin was present in all investigated samples. In the genus Allium, methiin
      dominated species (rarely used by man) were common, but the occurrence of the
      other cysteine sulphoxides was variable and was largely correlated with use as
      spices or vegetables. Two major chemical types (named according to the species
      where they occur) could be distinguished, and at least two more may be
      recognized. Isoalliin dominates in the widely used "onion-type", which includes
      chive (A. schoenoprasum) and top onion (A.xproliferum). Pearl onion and leek (A.
      ampeloprasum) have higher relative amounts of methiin and propiin, respectively.
      Alliin dominates in the widely used "garlic-type", which includes wild leek (A.
      obliquum) and sand leek (A. scorodoprasum). Alliin and isoalliin rarely co
      dominate, being only found in the cultivated Chinese leek (A. tuberosum). A
      triple mix of almost equal amounts of methiin, alliin and isoalliin is present in
      ramson (A. ursinum). General trends in the three evolutionary lines of the genus
      Allium were apparent. In the first lineage, high amounts of methiin were more
      frequent, and propiin, although being a minor component in all three evolutionary
      lines, was present in the highest amounts. Most of the species in the second line
      showed only traces of cysteine sulphoxides. In the third line, the "onion-type"
      dominates, the "garlic type" is characteristic for subgenus Allium, and co
      dominating alliin and isoalliin also occur. Generally, the total cysteine
      sulphoxide amount increased, and the complexity of cysteine sulphoxide patterns
      decreased in the transition from the first to the third evolutionary line.

PMID- 16626767
TI  - D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering
      ATPase activities and oxidative stress in guinea pigs.
AB  - Cisplatin has been used as a chemotherapeutic agent to treat many kinds of
      malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been
      reported. However, the underlying biochemical change in the inner ear or central
      vestibular nervous system is not fully understood. In this study, we attempted to
      examine whether cisplatin-induced vestibulotoxicity and D-methionine protection
      were correlated with the changes of ATPase activities and oxidative stress of
      ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory
      center of VOR system) of guinea pigs. By means of a caloric test coupled with
      electronystagmographic recordings, we found that cisplatin exposure caused a dose
      dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of
      slow phase velocity (SPV). In addition, cisplatin significantly inhibited the
      Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the ampullary tissue with a
      good dose-response relationship but not those of cerebellar cortex. Regression
      analysis indicated that a decrease of SPV was well correlated with the reduction
      of Na(+), K(+)-ATPase and Ca(2+)-ATPase activities of the ampullary tissue. D
      Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in
      a correlated manner. Moreover, cisplatin exposure led to a significant dose
      dependent increase of lipid peroxidation and nitric oxide concentrations of the
      vestibules, which could be significantly suppressed by D-methionine. However,
      cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the
      cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased
      oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated
      cisplatin-induced vestibulotoxicity associated with ionic disturbance through its
      antioxidative property.

PMID- 16626768
TI  - A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.
AB  - Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors
      in the rat. To elucidate the mode of action for tumor formation, the effect of
      Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine
      UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats
      were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats
      diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42
      days and for 42 days followed by 42 days of reversal. As a positive control, rats
      were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7
      and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats
      with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased
      thyroid gland weights, which were associated with follicular cell hypertrophy.
      Thyroid follicular cell replicative DNA synthesis was increased by treatment with
      Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB
      increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and
      serum thyroid stimulating hormone levels (TSH), but reduced serum levels of
      either thyroxine (T4) and/or triiodothyronine (T3). The effects of Pyrethrins in
      female rats were dose-dependent, with 100 ppm being a no-effect level, and on
      cessation of treatment were essentially reversible in both sexes. The concordance
      between the effects of Pyrethrins and NaPB suggests that the mode of action for
      Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non
      genotoxic inducers of hepatic xenobiotic metabolism.

PMID- 16626769
TI  - Ochratoxin A in human blood in Abidjan, Cote d'Ivoire.
AB  - Ochratoxin A (OTA) produced by Aspergillus and Penicillium genera contaminates a
      diversity of foods including cereals; cereals-derived foods; dry fruits; beans;
      cocoa; coffee; beer; wine; and foodstuffs of animal origin mainly poultry, eggs,
      pork and milk, including human breast milk. OTA is nephrotoxic to all animal
      species studied so far and most likely to humans, who show the longest half-life
      for elimination of this toxin among all species examined. Among other toxic
      effects, OTA is teratogenic, immunotoxic, genotoxic, mutagenic and carcinogenic,
      all of which lead to life-threatening pathologies through several molecular
      pathways. In Cote d'Ivoire, preliminary surveys conducted by us have proven from
      1998 to 2004 the reality of ochratoxin A-contamination of foodstuffs. To assess
      OTA in human blood, the immunoaffinity columns were used along with HPLC for
      separation and fluorimetric quantification of blood samples collected in Abidjan
      from two categories of people: apparently healthy donors (n=63) and nephropathy
      patients undergoing dialysis (n=39). Among healthy donors, 34.9% show OTA
      concentrations ranging from 0.01 - 5.81 microg/l with a mean value of 0.83
      microg/l, whereas, among nephropathy patients undergoing dialysis 20.5% are OTA
      positive in a range of 0.167-2.42 microg/l and a mean value of 1.05. Although the
      sex ratio is 0.82 (46 females for 56 males) ochratoxin A contamination is equally
      distributed in both sexes. Nephropathy patients undergoing dialysis appear,
      however, less frequently contaminated than healthy donors (20.5 versus 34.9%) and
      show higher OTA concentrations (higher mean value, p=0.01). Ochratoxin A
      concentrations found in human blood reflect concentrations previously detected in
      cereals and peanuts according to the eating habits and diets of people in Cote
      d'Ivoire. But, the prevalence of ochratoxin A in blood of nephropathy people
      undergoing dialysis appears lower than expected from the frequency of OTA
      contamination in cereals and peanuts. Pearson chi(2)-test indicates that among
      OTA-positive individuals renal dialysis and age are important modalities for
      consideration.

PMID- 16626770
TI  - LC/ESI/MS method development for the analysis of hepatotoxic cyclic peptide
      microcystins in animal tissues.
AB  - Microcystins (MCYSTs) are a family of related cyclic heptapeptides produced by
      several genera and species of blue-green algae (cyanobacteria). MCYSTs are potent
      and specific inhibitors of the serine threonine family of protein phosphatases,
      especially PP1 and PP2A. MCYSTs inhibit a liver's protein phosphatase by forming
      a covalent linkage between MCYSTs' Mdha residue and the phosphatase's cysteine
      residue. Due to the covalent linkage, analysis of MCYSTs in animal tissues has
      been limited to determination of unbound MCYST concentration. The MMPB (2-methyl
      3-methoxy-4-phenylbutyric acid) oxidation procedure allows for the detection of
      total MCYST burden by releasing the carboxylic acid MMPB from MCYST's Adda amino
      acid. An internal standard 4-phenylbutyric acid (4PB) accounts for losses during
      the method. LC/MS conditions were developed using a ThermoFinnigan LCQDuo ion
      trap in negative electrospray ionization (ESI). Since both compounds produce the
      [M-H](-) ion, analysis occurs in selected ion monitoring (SIM) mode for both MMPB
      (m/z 207.1) and 4PB (m/z 163.1). Complete oxidation of MCYST-LR in liver tissues
      occurs in 3h. A solid phase extraction (SPE) cartridge removes MMPB and 4PB from
      the oxidant solution. The process efficiency for the SPE procedure is only 51.3%;
      however, suppression experiments indicate a 41.8% loss in signal strength due to
      matrix interferences. Therefore, the extraction efficiency for the SDB-XC
      cartridge procedure is 93.1%. This research has been successful in developing an
      LC/MS method for the analysis of total MCYST burden in animal tissues.

PMID- 16626771
TI  - Effects of veratrine and veratridine on oxygen consumption and electrical
      membrane potential of isolated rat skeletal muscle and liver mitochondria.
AB  - We have previously shown that veratrine, a mixture of alkaloids known as Veratrum
      alkaloids, produces skeletal muscle toxicity, and there is evidence that
      veratrine interferes with the energetics of various systems, including
      cardiomyocytes and synaptosomes. In this work, we explored the effects of
      veratrine and veratridine, a component of this mixture, in rat skeletal muscle
      mitochondria and compared the results with those seen in liver mitochondria.
      Veratrine and veratridine alkaloids caused a significant concentration-dependent
      decrease in the rate of state 3 respiration, respiratory control (RCR) and ADP/O
      ratios in isolated rat skeletal muscle mitochondria (RMM), but not in rat liver
      mitochondria (RLM) supported by either NADH-linked substrates or succinate. The
      oxygen consumption experiments showed that RMM were more susceptible to the toxic
      action of Veratrum alkaloids than RLM. The addition of veratrine (250 microg/ml)
      to RMM caused dissipation of the mitochondrial electrical membrane potential
      during succinate oxidation, but this effect was totally reversed by adding ATP.
      These results indicate that there are chemical- and tissue-specific toxic effects
      of veratrine and veratridine on mitochondrial respiratory chain complexes.
      Identification of the specific respiratory chain targets involved should provide
      a better understanding of the molecular mechanisms of the toxicity of these
      agents.

PMID- 16626772
TI  - Releasing or expression modulating mediator involved in hemostasis by
      Berythractivase and Jararhagin (SVMPs).
AB  - PIII snake venom metalloproteases (SVMPs) are structurally related to ADAMs (a
      disintegrin and metalloprotease human family of proteins). Berythractivase and
      Jararhagin are PIII SVMPs with 69% homology with different hemostatic properties.
      In order to clarify these differences and further characterize the biological
      effects of these proteins, we compared the effect of both proteases on human
      umbilical vein endothelial cell (HUVEC) for evaluating the release and modulation
      of coagulation and fibrinolysis mechanisms as well as the expression of their
      correlated genes. We found that both proteins increase the von Willebrand factor
      liberation, but did not modulate gene expression. Berythractivase, differently
      from Jararhagin increased the expression of tissue factor. Our results showed
      that both SVMPs (Berythractivase and Jararhagin) activate HUVEC releasing or
      modulating mediators involved in hemostasis. Meanwhile, we can suggest through
      the up-regulation of TF gene that the studied SVMP acts in a specific manner,
      suggesting that Jararhagin has preferentially a local action, while
      Berythractivase can be assumed as a systemic pro-coagulant protein with activity
      on the surface of HUVECs.

PMID- 16626773
TI  - Effect of microcystin on leukocyte viability and function.
AB  - Microcystin (MC) has been found in several areas of the world. In addition to its
      hepatotoxicity, microcystin may have an immunomodulatory effect. Considering that
      patients receiving hemodialysis may be chronically exposed to variable
      concentrations of MC, and that they present important changes in this immune
      response, we have assessed the effect of MC on the function of leukocytes.
      Polymorphonuclear leukocytes isolated from healthy volunteers (HV) and patients
      receiving hemodialysis (HD) were incubated with microcystin (10 microg/L) for 24h
      and evaluated for reactive oxygen species production (ROS), phagocytosis and
      apoptosis. Monocytes incubated with and without LPS (100 ng/mL) and microcystin
      for 24h were assessed for TNFalpha and IL-10 production. Leukocytes of HV
      presented an increase in apoptosis rates and leukocytes from HD exhibited a lower
      production of oxygen-reactive species, both spontaneously and after stimulus with
      S. aureus, when compared with leukocytes incubated without toxin. Monocytes
      presented an increase in cytokine production after stimulation by LPS in both
      groups, but there was no difference between the groups with and without MC that
      were incubated with or without LPS. Low concentrations of microcystin can induce
      mild changes in leukocyte function of HV and HDP, particularly in the ability to
      produce ROS.

PMID- 16626774
TI  - Azaspiracid-1 inhibits bioelectrical activity of spinal cord neuronal networks.
AB  - Azaspiracid-1 (AZA-1) is a recently identified phycotoxin that accumulates in
      molluscs and can cause severe human intoxications. For this study, we utilized
      murine spinal cord and frontal cortex neuronal networks grown over 64 channel
      microelectrode arrays (MEAs) to gain insights into the mechanism of action of AZA
      1 on neuronal cells. Extracellular recordings of spontaneous action potentials
      were performed by monitoring mean spike rate as an assay of the efficacy of AZA-1
      to alter the bioelectrical activity of neurons in the networks. Via slow onset,
      AZA-1 decreased the mean spike rate of the spinal cord neurons with an IC(50) of
      ca. 2.1nM, followed by partial recovery of original activity when toxin was
      removed. Pre-treatment with the GABA(A) receptor antagonist bicuculline led to an
      increased response of the neuronal networks to AZA-1 exposure and resulted in an
      irreversible inhibition of spike rate. AZA-1 did not cause any changes in frontal
      cortex networks upon drug exposure. In addition, whole-cell patch clamp
      recordings from spinal cord neurons showed that AZA-1 had no significant effect
      on the voltage-gated sodium (Na(+)) or calcium (Ca(2+)) currents, suggesting that
      the toxin affected synaptic transmission in the neuronal networks through a
      mechanism independent of these voltage-gated channels.

PMID- 16626775
TI  - Toxic potential of microcystin-containing cyanobacterial extracts from three
      Romanian freshwaters.
AB  - The aim of this study was to characterise for the first time the toxin profile
      and in vivo/in vitro toxicological effects of cyanobacteria obtained from three
      Romanian freshwater blooms. Two strains of Microcystis aeruginosa were isolated
      from blooms occurring in different fish ponds. As well, a complex bloom sample
      obtained from a recreational lake area and dominated by Microcystis aeruginosa
      and Microcystis viridis was explored. The morphological identity of the
      cyanobacterial species could be confirmed by sequence analysis of the intergenic
      spacer region of the phycocyanin operon, PC-IGS. As well, both the strains and
      the field sample were confirmed to possess mcyA and mcyB genes, which correlated
      with the formation of several microcystins (MCYSTs). A number of cyanopeptolins
      and a new aeruginosin were also found. Despite these mixtures of compounds, in
      vivo as well as in vitro toxicological responses resembled those previously found
      for MCYST-LR. These include strong hepatotoxicity in mice with parenchymal
      disintegration and the emergence of haemorrhagic centres, a lack of
      responsiveness of human and fish cell lines most likely due to a lack of active
      transport systems, and a significant subcellular damage most prominent on the
      level of the lysosomes in primary hepatocytes of mice and rainbow trout. We thus
      conclude that the formation of blooms in the Romanian fish ponds and the
      recreational area may impact on animal and human health. A broader survey of
      cyanotoxin occurrence and related toxicity is necessary in Romania in order to
      assess the extent of this animal and human health hazard.

PMID- 16626776
TI  - Functional characterization of a basic D49 phospholipase A2 (LmTX-I) from the
      venom of the snake Lachesis muta muta (bushmaster).
AB  - The whole venom of Lachesis muta muta is preponderantly neurotoxic but moderately
      myotoxic on the chick biventer cervicis preparation (BCp). We have now examined
      these toxic activities of a basic phospholipase A(2), LmTX-I, isolated from the
      whole venom. LmTX-I caused a significant concentration-dependent neuromuscular
      blockade in the BCp. The time to produce 50% neuromuscular blockade was 14.7+/
      0.75 min (30 microg/ml), 23.6+/-0.9 min (10 microg/ml), 34+/-1.7 min (2.5
      microg/ml) and 39.2+/-3.6 min (1 microg/ml), (n=5/concentration; p<0.05).
      Complete blockade with all tested concentrations was not accompanied by
      inhibition of the response to ACh. At the highest concentration, LmTX-I (30
      microg/ml) significantly reduced contractures elicited by exogenous KCl (20mM),
      increased the release of creatine kinase (1542.5+/-183.9 IU/L vs 442.7+/-39.8
      IU/L for controls after 120 min, p<0.05), and induced the appearance of
      degenerating muscle fibers ( approximately 15%). Quantification of myonecrosis
      indicated 14.8+/-0.8 and 2.0+/-0.4%, with 30 and 10 microg/mlvenom concentration,
      respectively, against 1.07+/-0.4% for control preparations. The findings indicate
      that the basic PLA(2) present on venom from L. m. muta (LmTX-I) possesses a
      dominant neurotoxic action on isolated chick nerve-muscle preparations, whereas
      myotoxicity was mainly observed at the highest concentration used (30 microg/ml).
      These effects of LmTX-I closely reproduce the effects of the whole venom of L. m.
      muta in chick neuromuscular preparations.

PMID- 16626777
TI  - Mass spectrometry strategies for venom mapping and peptide sequencing from crude
      venoms: case applications with single arthropod specimen.
AB  - Due to their complexity and diversity, animal venoms represent an extensive
      source of bioactive compounds such as peptides and proteins. Conventional
      approaches for their characterization often require large quantities of
      biological material. Current mass spectrometry (MS) techniques now give access to
      a wealth of information in a short working time frame with minute amounts of
      sample. Such MS approaches may now be used for the discovery of novel compounds,
      and once their structure has been determined they may be synthesized and tested
      for functional activity. Molecular mass fingerprints of venoms allow the rapid
      identification of known toxins as well as preliminary structural characterization
      of new compounds. De novo peptide sequencing by tandem mass spectrometry (MS/MS)
      offers rapid access to partial or total primary peptide structures. This article,
      written as a tutorial, also contains new material: molecular mass fingerprint
      analysis of Orthochirus innesi scorpion venom, and identification of components
      from bumblebee Bombus lapidarius venom, both collected from one single specimen.
      The structure of the three major peptides detected in the Bombus venom was fully
      characterized in one working day by de novo sequencing using an electrospray
      ionization hybrid quadrupole time-of-flight instrument (ESI-QqTOF) and a matrix
      assisted laser desorption ionization time-of-flight instrument (MALDI-LIFT-TOF
      TOF). After presenting the MS-based sequence elucidation, perspectives in using
      MS and MS/MS techniques in toxinology are discussed.

PMID- 16626778
TI  - In situ electrochemical and photo-electrochemical generation of the fenton
      reagent: a potentially important new water treatment technology.
AB  - In this work, the design and construction of an annular tube reactor for the
      electrochemical and photo-electrochemical in situ generation of H2O2 are
      described. By cathodic reduction of dissolved oxygen and the coupled oxidation of
      water at a UV-illuminated nanocrystalline-TiO2 semiconductor anode, it was found
      that the electrochemically generated H2O2 can be employed to readily oxidize the
      model compound Direct Yellow-52 in dilute acidic solution at high rates in the
      presence of small quantities of dissolved iron(II). Although, the model organic
      compound is chemically stable under UV radiation, its electrochemical oxidation
      rate increases substantially when the semiconductor anode is illuminated as
      compared to the same processes carried out in the dark.

PMID- 16626779
TI  - The influence of physical-chemical and biological factors on the removal of
      faecal coliform through down-flow hanging sponge (DHS) system treating UASB
      reactor effluent.
AB  - The mechanism of faecal coliform removal in down-flow hanging sponge (DHS) system
      treating up-flow anaerobic sludge blanket (UASB) reactor effluent was the subject
      of this study. The results obtained revealed that the most important removal
      mechanism of faecal coliform in the DHS system is adsorption, followed by
      predation. Die-off is a relatively minor removal mechanism in the DHS system. The
      impact of physical and chemical factors such as contact time, effective sponge
      bulk volume and pH values on faecal coliform removal has been investigated.
      Increasing the contact time and sponge bulk volume exerted positive effect on the
      removal of faecal coliform. Changing the pH values between 6.5 and 9.0 did not
      show significant impact. Reducing sponge pore size from 1.92 to 0.56 mm,
      increased faecal coliform removal by a value of 1.3 log10.

PMID- 16626780
TI  - Permeabilities of anaerobic CH4-producing granules.
AB  - The permeability of anaerobic CH4-producing granules was investigated with both
      settling and size exclusion chromatography experiments. The experimental results
      indicate that the two methods could be successfully applied to evaluate the
      permeability of the CH4-producing granules. An interdependent relationship was
      found to exist between the two methods for explaining the permeability of the
      granules. Both methods demonstrate that the porosity of the CH4-producing
      granules decreased with increasing size, while their settling velocities had an
      opposite trend. Extracellular polymeric substances yielded by the anaerobic
      microorganisms might clog the pores within the granules, resulting in a reduction
      in their porosities. The experimental results also suggest that molecular
      diffusion appeared to play an important role in the mass transfer in and/or
      through the granules.

PMID- 16626781
TI  - Evaluation of in situ layers for treatment of acid mine drainage: a field
      comparison.
AB  - Reactive treatment layers, containing labile organic carbon, were evaluated to
      determine their ability to promote sulfate reduction and metal sulfide
      precipitation within a tailings impoundment, thereby treating tailings effluent
      prior to discharge. Organic carbon materials, including woodchips and pulp waste,
      were mixed with the upper meter of tailings in two separate test cells, a third
      control cell contained only tailings. In the woodchip cell sulfate reduction
      rates were 500 mg L-1a-1, (5.2 mmol L-1a-1) this was coupled with the gradual
      removal of 350 mg L-1 Zn (5.4 mmol L-1). Decreased delta13CDIC values from -3 per
      thousand to as low as -12 per thousand indicated that sulfate reduction was
      coupled with organic carbon oxidation. In the pulp waste cell the most dramatic
      change was observed near the interface between the pulp waste amended tailings
      and the underlying undisturbed tailings. Sulfate reduction rates were 5000 mg L
      1a-1 (52 mmol L-1a-1), Fe concentrations decreased by 80-99.5% (148 mmol L-1) and
      Zn was consistently <5 mg L-1. Rates of sulfate reduction and metal removal
      decreased as the pore water migrated upward into the shallower tailings.
      Increased rates of sulfate reduction in the pulp waste cell were consistent with
      decreased delta13CDIC values, to as low as -22 per thousand, and increased
      populations of sulfate reducing bacteria. Lower concentrations of the nutrients,
      phosphorus, organic carbon and nitrogen in the woodchip material contribute to
      the lower sulfate reduction rates observed in the woodchip cell.

PMID- 16626782
TI  - Effect of clay content and wetting-and-drying on radiocaesium behaviour in a peat
      and a peaty podzol.
AB  - The interaction of radiocaesium with peat under two moisture regimes was studied
      in laboratory experiments and by growing ryegrass in pot experiments to simulate
      changing field moisture conditions. A peat untreated and treated with 5% by
      weight of clay containing 46% illitic minerals, and a peaty podzol naturally
      containing 4.5% mineral matter on a dry weight basis were contaminated with
      (134)Cs and incubated. The soils were exposed to 8 wetting-and-drying cycles or
      kept constantly wet during 40 days. Extraction of the peat with 1 M CH(3)COONH(4)
      (pH 7) repeated after each wetting-and-drying cycle indicated increasing (134)Cs
      fixation with time of incubation. The peat treated with clay showed a much higher
      (134)Cs fixation than that without clay. The pot experiment with the incubated
      soils showed a (134)Cs transfer to ryegrass of the same order for the peaty
      podzol as for the peat treated with clay. For the peat untreated with clay the
      (134)Cs transfer to ryegrass was much greater. Wetting-and-drying the peat, with
      or without clay, increased the overall yield of grass and the concentration and
      uptake of (134)Cs over 5 consecutive harvests. K-fertilisation increased the
      yield of plant material (except for the peat with added clay), decreased the
      concentration of (134)Cs, but had no significant effect (p=0.05) on the resultant
      uptake of (134)Cs. Mixing clay with the surface layer of organic soils appears to
      be an effective means of decreasing radiocaesium transfer to field crops in
      fallout situations.

PMID- 16626783
TI  - Chlorophyll-a in the rivers of eastern England.
AB  - Chlorophyll-a concentration variations are described for two major river basins
      in England, the Humber and the Thames and related to catchment characteristics
      and nutrient concentrations across a range of rural, agricultural and
      urban/industrial settings. For all the rivers there are strong seasonal
      variations, with concentrations peaking in the spring and summer time when
      biological activity is at its highest. However, there are large variations in the
      magnitude of the seasonal effects across the rivers. For the spring-summer low
      flow periods, average concentrations of chlorophyll-a correlate with soluble
      reactive phosphorus (SRP). Chlorophyll-a is also correlated with particulate
      nitrogen (PN), organic carbon (POC) and suspended sediments. However, the
      strongest relationships are with catchment area and flow, where two straight line
      relationships are observed. The results indicate the importance of residence
      times for determining planktonic growth within the rivers. This is also indicated
      by the lack of chlorophyll-a response to lowering of SRP concentrations in
      several of the rivers in the area due to phosphorus stripping of effluents at
      major sewage treatment works. A key control on chlorophyll-a concentration may be
      the input of canal and reservoir waters during the growing period: this too
      relates to issues of residence times. However, there may well be a complex series
      of factors influencing residence time across the catchments due to features such
      as inhomogeneous flow within the catchments, a fractal distribution of stream
      channels that leads to a distribution of residence times and differences in
      planktonic inoculation sources. Industrial pollution on the Aire and Calder seems
      to have affected the relationship of chlorophyll-a with PN and POC. The results
      are discussed in relation to the Water Framework Directive.

PMID- 16626784
TI  - Arsenic speciation in moso bamboo shoot--a terrestrial plant that contains
      organoarsenic species.
AB  - Arsenic is predominantly found as an inorganic species in most terrestrial
      plants. However, we found that a significant proportion of organic arsenic was
      present in moso bamboo (Phyllostachys pubescens Mazel) shoot in a market survey
      of arsenic species in edible terrestrial plants. Moso bamboo shoots from
      different producing areas in China were collected for analysis to confirm the
      ubiquity of methylated arsenic species. The total arsenic concentrations of
      bamboo shoots were determined by hydride generation coupled atomic fluorescence
      spectrometry (HG-AFS), ranging from 27.7 to 94.0 microg/kg. Information about
      arsenic species was acquired from cold trap-hydride generation-atomic absorption
      spectrometry (CT-HG-AAS). Dimethylarsinic acid (DMA) was present in the amount of
      13.9% to 44.9% of sum of the arsenic species in all these samples.
      Monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) were also detected
      in certain samples in the range of 4.2-16.5% and 11.8-18.4%, respectively. In
      addition, bamboo shoots collected in winter were found to have more total arsenic
      and organic arsenic than those collected in spring. To investigate the source of
      the organic arsenic in moso bamboo shoots, arsenic species in the rhizosphere
      soils of the plants were examined. The absence of organic arsenic in soils would
      suggest the possibility of formation of methylated arsenic in the plants. In
      addition, studies of arsenic speciation in the peel and core of winter bamboo
      shoots showed that all the cores contained organic arsenic while no organic
      arsenic was detected in the peels. The study provides useful information for
      better understanding of the distribution of arsenic species in terrestrial
      plants.

PMID- 16626785
TI  - Detoxification of selenite and mercury by reduction and mutual protection in the
      assimilation of both elements by Pseudomonas fluorescens.
AB  - A study on the assimilation and detoxification of selenium and mercury and on the
      interaction between these two elements was conducted on Pseudomonas fluorescens.
      P. fluorescens was able to convert separately both elements to their elemental
      forms, which are less toxic and biologically less available. To study the
      converting mechanism of selenite to elemental Se, cells were grown in the
      presence of various selenite concentrations and several parameters such as
      extracellular protein concentrations, pH, carbohydrate concentrations, isocitrate
      dehydrogenase (ICDH) and malic enzyme were monitored. Transmission electron
      microscopy (TEM) and various analytical methods were applied to confirm the
      interaction between selenium and cell. The former appeared as a red precipitate
      localized predominantly in the consumed culture medium. P. fluorescens also
      resisted to the toxic effect of mercury by converting Hg2+ to the volatile and
      less toxic form Hg0. Mercury reductase was likely responsible for the conversion
      of Hg2+ to Hg0. More importantly, the interaction between mercury and selenium
      was also studied. The presence of selenite significantly reduced the accumulation
      of mercury in P. fluorescens. It was also interesting to note that mercury
      appeared to behave as a protecting agent against selenium intoxication as the
      bioaccumulation of Se was also inhibited by this metal. The formation of Se-Hg
      complexes could explain this mutual protective effect. No precipitate of
      elemental Se could be detected when Hg was present in the cultures.

PMID- 16626786
TI  - Stream fish assemblages and basin land cover in a river network.
AB  - This study focused on characterizing fish assemblages in the Adour-Garonne basin
      and identifying the relative influences of landscape-scale features on observed
      patterns in stream fish assemblages. Two different artificial neural network
      algorithms were used: a self-organizing map (SOM) and a multilayer perceptron
      (MLP). A SOM was applied to determine fish assemblage types, and a MLP was used
      to predict the fish assemblage types defined by the SOM. Thirty four species were
      collected at 191 sampling sites in a major river-system, the Adour-Garonne basin,
      and topographical factors, namely altitude, distance from source and surface area
      of drainage basin were measured. Using GIS, land cover types (agricultural land,
      forests and urbanized artificial surface) were calculated for each site and
      expressed as percentage of the surface area of basin. These variables were
      introduced to the MLP and factorial discriminant analysis for the prediction of
      assemblage types. As a result, the SOM distinguished three fish assemblage types
      according to the differences of species composition, and the assemblage types
      were better predicted with landscape-scale features by MLP than discriminant
      analysis. The percentages of agricultural land and the surface area of a basin
      showed the greatest influence on assemblage types 1 and 2, and distance from
      source was the most important factor to determine assemblage type 3.

PMID- 16626787
TI  - Cinnamaldehyde reduction of platelet aggregation and thrombosis in rodents.
AB  - INTRODUCTION: Cinnamaldehyde (CA) has been reported to inhibit in vitro
      aggregation in human and rabbit platelets; however, little is known about the
      antithrombotic activities of CA in vivo. MATERIALS AND METHODS: We tested the
      effects of CA on collagen- or thrombin-induced aggregation of rat platelets in
      vitro. Hemorrhage and coagulation times of mice treated with CA by the tail
      cutting or slide method were measured. We also tested the life-saving effects of
      CA on experimental models of thrombosis in mice and rats. The anti-platelet
      effects of CA were examined in rats. RESULTS: CA inhibited collagen- and thrombin
      induced platelet aggregation in vitro in a concentration-dependent manner. In
      mice, CA administration (250, 500 mg/kg orally and 50, 100 mg/kg i.p.) markedly
      prolonged hemorrhage and coagulation times and effectively reduced the mortality
      rate of collagen-epinephrine-induced acute pulmonary thromboembolism. In an
      arteriovenous shunt thrombosis rat model, the CA administration (250, 500 mg/kg
      orally and 50, 100 mg/kg i.p.) for 10 days dose-dependently decreased thrombus
      weight. Administration of CA also significantly inhibited collagen-induced
      platelet aggregation in the rat platelet-rich plasma (PRP). CONCLUSIONS: The
      results demonstrate that CA may be a promising antithrombotic agent, and its
      antithrombotic activity may be due to anti-platelet aggregation activity in vitro
      and in vivo.

PMID- 16626788
TI  - Ximelagatran: an eulogy.

PMID- 16626789
TI  - Abnormally sialylated fibrinogen gamma-chains in a patient with chronic
      thromboembolic pulmonary hypertension.

PMID- 16626790
TI  - Characterization of functional P2X(1) receptors in mouse megakaryocytes.
AB  - INTRODUCTION: Although accumulating evidence within the past 5 years strongly
      supports the importance of platelet P2X(1) receptors in hemostasis and
      thrombosis, P2X(1) receptors of platelet and/or its progenitor cell,
      megakaryocyte, have not been fully characterized. The aim of this study was to
      electrophysiologically and pharmacologically characterize the functional P2X(1)
      receptors on mouse megakaryocytes. MATERIALS AND METHODS: The currents in
      response to nucleotides were examined using the patch-clamp whole-cell recording.
      RESULTS: The agonist profile of megakaryocyte P2X(1) receptors was ATP>alpha,beta
      methylene ATP>beta,gamma-methylene ATP. The P2X(1) receptors exhibited
      substantial monovalent as well as divalent cation permeability and the ratios of
      Na(+) to Cs(+) and Ca(2+) to Cs(+) permeability were 1 and 2.5, respectively. P2X
      receptor antagonists except suramin significantly inhibited the P2X(1) responses
      with an IC(50) values of 0.4 microM for pyridoxal-phosphate-6-azophenyl-2',4'
      disulfonate (PPADS), 0.3 microM for 2',3'-O-(2,4,6-trinitophenyl)-adenosine 5'
      triphosphate (TNP-ATP), 20 microM for reactive blue 2 (RB2), or 160 microM for
      8,8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5
      naphthalenetrisulfonic acid) (NF023), respectively. Suramin had no significant
      effect on the P2X(1) responses. In rat megakaryocytes, suramin similarly had no
      significant effect on the P2X(1) responses, but abolished the P2Y receptor
      mediated responses, indicating that the suramin was active under present
      experimental condition. CONCLUSIONS: These results provide the basic properties
      of mouse megakaryocyte P2X(1) receptors and would be helpful to examine the P2
      receptor signaling in platelets and megakaryocytes.

PMID- 16626791
TI  - Evaluation of HPV 16 PCR detection in self- compared with clinician-collected
      samples in women referred for colposcopy.
AB  - OBJECTIVES: A clinical prospective evaluation study was conducted to evaluate PCR
      detection of high-risk human papillomavirus (HPV) type 16 in self-sampled vaginal
      compared with clinician-collected cervical specimens. METHODS: Paired vaginal and
      cervical specimens were collected from 137 consecutive women referred for
      colposcopy because of abnormal cervical cytology. In-house and a commercial PCR
      method for HPV type 16 were used. Self-sampled vaginal HPV 16 detection was
      compared to histology and physician-collected cervical specimens. RESULTS: Of the
      137 patients, 98 had proven abnormal histology and were included in the analysis.
      Overall, using the cervix HPV detection as reference method, the self-sampled
      vaginal sample showed sensitivity 91.8%, specificity 96.1% and agreement kappa
      (kappa) 0.881. Using the histology as reference, all 11 cervical cancer cases
      were HPV-16-positive in both cervical and vaginal samples, and in 43 high-grade
      lesions, detection sensitivity in cervix was 72.1% (kappa 0.588) and vagina 67.4%
      (kappa 0.516). HPV 16 detection did not differ (P=0.27) between clinician
      collected cervical and self-sampled vaginal specimens. CONCLUSIONS: The self
      collected vaginal sample is highly concordant with the physician-collected
      cervical sample in HPV 16 detection.

PMID- 16626792
TI  - A phase I trial of intraperitoneal sustained-release paclitaxel microspheres
      (Paclimer) in recurrent ovarian cancer: a Gynecologic Oncology Group study.
AB  - OBJECTIVES: Paclimer is a biodegradable polymer microsphere formulation
      containing 10% (w/w) paclitaxel that is designed to provide a sustained-release
      form of paclitaxel after intraperitoneal (IP) administration. The goals of this
      phase I study were to determine the maximum tolerated dose (MTD) of IP paclitaxel
      microspheres and the pharmacology of paclitaxel after IP paclitaxel microsphere
      administration. METHODS: Twelve patients with recurrent or persistent ovarian or
      primary peritoneal carcinoma were treated. After placement of an IP catheter,
      patients were treated with escalating doses of IP paclitaxel microspheres
      administered with 2 l of normal saline following premedication. Treatment could
      be repeated once, 8 weeks after initial treatment. The starting dose was 60 mg/m2
      and no intrapatient dose escalation was used. RESULTS: One dose-limiting toxicity
      consisting of abdominal pain, ileus and bowel obstruction was seen with the
      second cycle of therapy in one patient who received 900 mg/m2. Patients received
      up to 1200 mg/m2 without further evidence of dose-limiting toxicities (DLT). The
      study was discontinued before MTD was defined due to the manufacturer's decision
      to suspend further clinical development of paclitaxel microspheres.
      Pharmacokinetic analysis showed a trend toward a dose-dependent effect of IP
      paclitaxel microspheres on measured plasma paclitaxel levels. Sustained
      paclitaxel levels were maintained throughout all 8 weeks of therapy; however,
      paclitaxel concentrations were well below the plasma concentrations associated
      with toxicity. In one patient, laparoscopy revealed extensive adhesions, fat
      necrosis, foreign body giant cell reaction and detectable residual polymer
      filaments 7 months after completion of treatment with paclitaxel microspheres.
      CONCLUSIONS: IP administration of paclitaxel microspheres is well tolerated up to
      1200 mg/m2 without defining MTD. The low but persistent detection of plasma
      paclitaxel indicates that paclitaxel continues to be released for at least 8
      weeks after IP paclitaxel microsphere treatment. The finding of significant
      peritoneal abnormalities, including the presence of residual polymer filaments,
      months after IP Paclimer treatment suggests that the polymer preparation used in
      Paclimer degrades slowly.

PMID- 16626793
TI  - The impact of PET/CT in the management of recurrent ovarian cancer.
AB  - OBJECTIVES: To evaluate the impact of PET/CT on the restaging and management of
      recurrent ovarian cancer. METHODS: From January 2002 to July 2003, all women
      undergoing either surveillance or investigation of possible recurrent ovarian
      cancer at the Centre for Molecular Imaging, The Peter MacCallum Cancer Centre,
      were invited to take part in a prospective evaluation of the clinical impact of
      PET/CT. RESULTS: Fifty-six women having 66 scans were available for analysis. All
      patients had at least 12months follow-up after the PET/CT unless they died before
      that time. Apart from one equivocal scan, all scans performed in women with a
      CA125 higher than 35IU/ml had a positive PET/CT. PET/CT altered the known disease
      distribution in 40 scans (64%). Overall, PET/CT showed less disease in six scans
      (9%) and more disease in 34 scans (52%). Regardless of the value of CA125, PET/CT
      identified a sub group of women with apparently localized disease or no definite
      evidence of disease. This group showed improved survival compared with women
      shown to have systemic disease. PET/CT resulted in a major change of management
      plan in 34 patients (58%). CONCLUSION: PET/CT modifies the assessment of the
      distribution of recurrent ovarian cancer and alters patient management in a
      substantial proportion of patients. PET/CT appears to offer prognostic
      information.

PMID- 16626794
TI  - Modulation of anxiety by mu-opioid receptors of the lateral septal region in
      mice.
AB  - Morphine and opiates are known to exert anxiolytic effects, probably by
      interacting with the GABAergic system. The lateral septum (LS), mainly
      constituted of GABA neurons, exhibits high densities of mu-opiate receptors and
      could thus represent one the brain sites where opiates interact with GABAergic
      transmission to modulate anxiety. We examined the effects of intra-LS morphine
      injections on measures of anxiety using the elevated plus-maze and hole-board
      tests. Fos imaging was used to identify neural circuits involved in anxiety
      modulation. Unilateral intra-LS morphine (100 or 500 ng/100 nl) decreased open
      arm exploration in the plus-maze and reduced head-dipping frequency in the hole
      board, an anxiogenic-like effect associated with decreased Fos expression in the
      ventral LS, the dorsal hippocampus and the anterior hypothalamus. Anatomical
      specificity was assessed by injecting morphine into the medial septum, which
      failed to produce anxiogenesis. Pre-injection of the mu-opioid receptor
      antagonist naloxonazine (100 ng/100 nl) into LS reversed morphine-induced
      anxiogenesis and the associated pattern of Fos expression, indicating a specific
      recruitment of mu-opioid receptors by morphine. Surprisingly, bilateral morphine
      injections (20 to 500 ng/100 nl) were not found anxiogenic, perhaps due to their
      stimulant effect. Taken together, these results suggest that LS mu-opioid
      receptors participate to the modulation of anxiety.

PMID- 16626795
TI  - Performance of galanin transgenic mice in the 5-choice serial reaction time
      attentional task.
AB  - The neuropeptide galanin impairs learning and memory in rodents. The mechanism
      underlying the cognitive effects of galanin may be related to inhibitory effects
      of galanin on cholinergic transmission. As cholinergic function is thought to
      modulate sustained attention, the present study examined whether galanin
      overexpressing transgenic mice have impairments in sustained attention. Galanin
      transgenic (GAL-tg) mice and wild-type (WT) littermate controls were trained in a
      5-choice serial reaction time task, modified to assess sustained attention. GAL
      tg and WT mice performed similarly during acquisition with respect to accuracy,
      total omissions, and response speed. Attentional mechanisms were challenged by
      parametric changes including increased event rate, event asynchrony, or decreased
      stimulus duration. Singly, these challenges did not differentially affect
      performance between genotypes. Concurrent administration of these challenges,
      which represents an optimal test of sustained attention, also had similar effects
      on GAL-tg and WT mice. When stimulus discriminability was reduced by constant
      illumination of the house light, GAL-tg mice omitted more trials than WT mice,
      but other measures of performance did not differ by genotype. Moreover,
      intraventricular injection of galanin in WT mice did not affect sustained
      attention. These data indicate that previously reported learning and memory
      effects of galanin are not secondary to attentional dysfunction.

PMID- 16626796
TI  - Does worry about breast cancer predict screening behaviors? A meta-analysis of
      the prospective evidence.
AB  - OBJECTIVE: Many women worry about the possibility of developing breast cancer,
      but there is conflicting evidence concerning whether cancer worry acts as a
      facilitator or inhibitor of breast cancer screening. METHOD: We conducted a meta
      analysis of 12 prospective studies that measured worry about breast cancer at
      baseline and subsequent breast self-examination (BSE) or mammography utilization
      among 3342 high-risk and general population women. RESULTS: The data consistently
      show that breast cancer worry has a small but reliable (r = 0.12) association
      with breast cancer screening behavior, such that greater worry predicts a greater
      likelihood of screening. We also found that the means for breast cancer worry
      were consistently in the lower third of the scales, despite differences in
      measurement approaches, sample utilization, or the date that the study was
      conducted. CONCLUSION: The meta-analysis supports the contention that breast
      cancer worry may motivate screening behavior, and that high levels of breast
      cancer worry are uncommon.

PMID- 16626797
TI  - A process evaluation of a telephone-based peer-delivered smoking cessation
      intervention for adult survivors of childhood cancer: the partnership for health
      study.
AB  - OBJECTIVE: We report on the process evaluation of an efficacious national smoking
      cessation intervention for adult survivors of childhood cancer. We examine
      associations between intervention implementation characteristics and study
      outcomes, as well as participant characteristics related to level of involvement
      in the intervention. METHODS: The study was conducted at the Dana-Farber Cancer
      Institute in Boston, Massachusetts, from 1999-2001. Participants (n = 398) were
      randomly assigned to receive a proactive telephone-based peer counseling
      intervention. They received up to 6 counseling calls, individually tailored and
      survivor-targeted materials, and nicotine replacement therapy (NRT) patches if
      they were prepared to quit smoking. RESULTS: Forty-two percent of survivors
      participated in the maximum number of calls (5-6), and 29% of participants
      requested and received NRT. Total counseling time was an average of 51 min. Quit
      status at follow-up was related to intervention dose, and participants who
      received NRT were significantly more likely to make a 24-h quit attempt.
      Demographic variables (females, White), higher daily smoking rate, poorer
      perceived health and moderate perceived risk of smoking were significantly
      related to greater intervention involvement. CONCLUSIONS: A brief peer-delivered,
      telephone counseling intervention is an effective way to intervene with adult
      survivors of childhood cancer who are smoking. Findings from the process
      evaluation data (call length and number, frequency, and spacing) will inform
      future telephone counseling cessation programs.

PMID- 16626798
TI  - In vitro thermal stress induces apoptosis and reduces development of porcine
      parthenotes.
AB  - The precise physiological causes that result in reduced development of oocytes
      after heat shock (HS) are not clear. In this study, apoptosis, heat shock
      protein70 (hsp70), and in vitro development of porcine oocytes were evaluated
      after HS. Porcine cumulus-oocyte complexes (COCs) were subjected to in vitro
      maturation for 42 h. The matured oocytes were then heated at 41.5 degrees C for 0
      h (control, C0h), 1 h (HS1h), 2 h (HS2h), or 4 h (HS4h). An additional group of
      oocytes was cultured for 4 h without HS (control, C4h). In Experiment 1,
      expression of hsp70 was detected by Western-blotting and no difference between
      controls and HS groups was observed. In Experiment 2, apoptosis of matured
      oocytes after HS was examined by Annexin V-FITC and TUNEL. No significant TUNEL
      positive signals were detected in the heated oocytes compared to the controls,
      but the intensity of Annexin V-FITC labeling among different groups increased
      with length of HS and in vitro culture (P<0.05). Oocytes were parthenogenetically
      activated by an electric pulse plus 6-DMAP (Experiment 3). Mean (+/-S.E.M.)
      embryonic development in HS2h (cleavage: 42+/-29%; blastocyst: 11+/-10%) and HS4h
      (cleavage: 36+/-28%; blastocyst: 11+/-8%) were decreased when compared to those
      in C0h (cleavage: 63+/-12%; blastocyst: 24+/-14%) and C4h (cleavage: 66+/-8%;
      blastocyst: 21+/-11%). Numbers of blastocysts with TUNEL-positive signals were
      similar among groups, but the signals increased before the eight-cell stage in HS
      groups (P<0.05). In conclusion, developmental competence of matured pig oocytes
      was compromised after heat shock, but it was not closely associated with the
      expression of oocyte hsp70. However, there may be a link between apoptosis and
      developmental competence of porcine oocytes.

PMID- 16626799
TI  - Contraception in felids.
AB  - Contraceptives are used for reversible reproductive control in genetically
      valuable wild felids, as permanent reproductive control in generic wild felids,
      and as an economically practicable means to control feral cats. The progestin
      contraceptives, megestrol acetate, melengesterol acetate, medroxyprogesterone
      acetate, and levonorgestrol (administered orally, in implants, or as depot
      injections), are effective in preventing pregnancy. However, long-term use is
      associated with endometrial hyperplasia, endometrial cancer, and mammary cancer.
      Gonadotropin releasing hormone analogs or luteinizing hormone vaccines that
      achieve contraception by suppressing ovarian or testicular function, do not have
      the adverse health effects of progestins. However, reliable reversibility has not
      been demonstrated, and male secondary sex characteristics may be suppressed.
      Bisdiamines also inhibit spermatogenesis and lower circulating testosterone
      concentrations in treated male cats. Porcine zona pellucida vaccines are
      ineffective contraceptives in felids and may cause serious health problems when
      combined with some adjuvants. Because of the limited availability of non
      progestin contraceptives and side effects associated with some agents, widespread
      application of contraception to felids has been curtailed. More non-steroidal
      methods of contraception should be tested in the future to provide alternatives
      for controlling reproduction in felids. Furthermore, all empirical information on
      contraceptive safety and efficacy should be assembled in a database to provide
      the knowledge needed by veterinarians and managers to determine benefits/risks of
      currently available contraceptives in felids, both domestic and wild.

PMID- 16626800
TI  - Positive career orientation as an inhibitor of adolescent problem behaviour.
AB  - This study tested the hypothesis that positive career orientation can prevent
      adolescents from engaging in or escalating problem behaviour. A 1-year,
      longitudinal study was conducted on a sample of 234 junior-high and high-school
      students, who were 14.8 years old on the average in the beginning of the study.
      Using structural equation modeling, a developmental, two-wave, two-factor
      empirical model corresponding to the predicted relationships between career
      orientation and problem behaviour was found to fit the data well. According to
      the fitted model, positive career orientation had a significant negative
      longitudinal effect on problem behaviour. In contrast, we found no evidence in
      support of the assumption that career orientation can be affected by problematic
      behavioural tendencies.

PMID- 16626801
TI  - Trophic structure and functioning in a eutrophic and poorly flushed lagoon in
      southwestern Taiwan.
AB  - Tapong Bay, a eutrophic and poorly flushed tropical lagoon, supports intensive
      oyster culture. Using the Ecopath approach and network analysis, a mass-balanced
      trophic model was constructed to analyze the structure and matter flows within
      the food web. The lagoon model is comprised of 18 compartments with the highest
      trophic level of 3.2 for piscivorous fish. The high pedigree index (0.82) reveals
      the model to be of high quality. The most-prominent living compartment in terms
      of matter flow and biomass in the lagoon is cultured oysters and bivalves,
      respectively. The mixed trophic impacts indicate that phytoplankton and
      periphyton are the most-influential living compartments in the lagoon.
      Comparative analyses with the eutrophic and well-flushed Chiku Lagoon and non
      eutrophic tropical lagoons show that high nutrient loadings might stimulate the
      growth and accumulation of phytoplankton and periphyton and therefore support
      high fishery yields. However, net primary production, total biomass, fishery
      yields per unit area, and mean transfer efficiency of Tapong Bay were remarkably
      lower than those of Chiku Lagoon. The lower transfer efficiency likely results
      from the low mortality of cultured oysters and invasive bivalves from predation
      or the lower density of benthic feeders constrained by the hypoxic bottom water
      as a result of poor flushing. This might therefore result in a great proportion
      of flows to detritus. However, the hypoxic bottom water might further reduce the
      recycling of the entering detritus back into the food web. In contrast to many
      estuaries and tropical lagoons, poor flushing of this eutrophic tropical lagoon
      might induce a shift from detritivory to herbivory in the food web.

PMID- 16626802
TI  - Matrix-assisted refolding of oligomeric small heat-shock protein Hsp26.
AB  - Recombinant gene expression in the prokaryotic host Escherichia coli is of
      general interest for both biotechnology and basic research. Use of E. coli is
      inexpensive and advantageous due to the fully developed genetic accessibility.
      However, often insoluble target protein (inclusion body) accumulates in the cell.
      Especially when producing eukaryotic or disulfide bridged proteins in E. coli,
      inclusion body formation is observed. Nonetheless, insoluble protein can be
      regained and refolded in vitro. Commonly, renaturation of proteins is
      accomplished by methods involving dilution and/or dialysis. An interesting
      alternative is matrix-assisted refolding in which the denatured protein is
      refolded in the immobilized state. Here, matrix-assisted refolding was applied to
      refold a double cysteine variant of Hsp26, a small heat-shock protein from
      Saccharomyces cerevisiae which was insoluble after biosynthesis in E. coli BL21
      (DE3) cells. This oligomeric protein was efficiently recovered from the insoluble
      fraction and refolded to its native oligomeric and chaperone-active state using
      ion exchange and size exclusion chromatography.

PMID- 16626803
TI  - Histamine regulates placental cytokine expression--in vivo study on HDC knockout
      mice.
AB  - Successful pregnancy is closely related to polarization toward a Th2 type immune
      response. As histamine is known to initiate Th2 dominance during inflammatory
      processes we raised the question whether histamine has any effect on the actual
      tuning of proper cytokine balance for the proceeding of the gestation. Histamine
      has multiple functions in the process of pregnancy, different studies have shown
      the direct and/or indirect presence of histamine action in the placenta as well.
      As HDC is the unique histamine producing enzyme in eukaryotes, we used HDC (so
      endogenous histamine)-deficient knockout mice as reliable model for studying
      histamine-related processes in vivo. We examined the placental histamine content
      and the expression of histamine receptors and Th1/Th2/Th3 type cytokines in the
      placenta. We showed for the first time the influence of histamine on the
      orchestrated regulation of placental cytokine expression. In the absence of local
      histamine the cytokine balance is shifted toward Th1 types at the maternal
      placental interface, threatening pregnancy. We also measured splenic lymphocyte
      subpopulation ratios in pregnant and non-pregnant mice and found that in
      pregnancy they are independent of the presence of histamine.

PMID- 16626804
TI  - Phenotypic and genetic characterization of enteropathogenic Escherichia coli
      (EPEC) and entero-aggregative E. coli (EAEC) from diarrhoeal and non-diarrhoeal
      children in Libya.
AB  - A total of 50 Escherichia coli strains isolated in a Libyan hospital (20 from
      children with diarrhoea and 30 from healthy children) were investigated for their
      pathotypes and virulence traits. Altogether nine eae-positive (enteropathogenic
      E. coli, EPEC) and nine aggR-positive (entero-aggregative E. coli, EAEC) strains
      were identified. Significantly (P=0.001) more EPEC strains were identified from
      diarrhoeal patients (n=8) than from healthy controls (n=1), while six EAEC
      strains were identified from diarrhoeal and three from healthy children. Typical
      (eae(+), EAF(+), bfp(+)) EPEC strains (n=6) belonged to classical EPEC serogroups
      O55, O114, O127 and showed localized adherence on Hela cells. EAEC strains
      revealed genetic heterogeneity but uniformly adhered to HeLa cultures in an
      entero-aggregative adherence pattern. Antibiotic resistance frequently,
      characterized the strains. Sixty-eight percentage of the strains were resistant
      against at least one antibiotic and 30% harbored a class 1 integron independently
      of their clinical background. This is the first report from North Africa
      demonstrating the significance of EPEC and EAEC.

PMID- 16626805
TI  - Uranium levels in the diet of Sao Paulo City residents.
AB  - Natural levels of uranium in the diet of Sao Paulo City residents were studied,
      and radionuclide concentrations were measured by the fission track method on
      samples of typical adult food items. This information was used to evaluate the
      daily intake of uranium in individuals living in Sao Paulo City which is,
      according to our findings, around 0.97 microg U/day. Using the ICRP Uranium
      model, we estimated the uranium accumulation and committed doses in some tissues
      and organs, as function of time. We compared the output of the ICRP uranium
      biokinetic model, tailored for the conditions prevailing in Sao Paulo, with
      experimental data from other localities. Such comparison was possible by means of
      a simple method we developed, which allows normalization among experimental
      results from different regions where distinct values of chronic daily intake are
      observed.

PMID- 16626806
TI  - Cytogenetic monitoring of domestic mammals exposed to wastewaters from the
      localities of Dladla and Boukallou near Settat, Morocco.
AB  - The aim of this work was to know the biological impact of wastewaters on
      livestock in the localities of Dladla and Boukallou (Town of Settat, Morocco),
      where wastewaters are largely used by the local population for their agricultural
      activities. We used the micronucleus (MN) test in cytochalasin B blocked
      binucleated cells (BNC) to assess the possible induced genetic effects. The
      cellular proliferation index (PI) was also calculated. Blood samples were
      collected from sheep, bovines and mules and peripheral blood cultures were made
      according to our laboratories' standard methodology. The results showed a
      significant increase of micronucleated cells in the lymphocytes of the exposed
      animals (14+/-8.79 MN/500 BNC) compared to the control (3+/-1.54 MN/500 BNC). The
      PI showed a nonsignificant decrease in the exposed animals. The highest MN
      frequency was found in mules which is probably due to their more sedentary life.
      Direct use of the wastewater by the animals as their source of drinking water
      significantly increased the frequency of cells with micronuclei. We also
      established an inverse correlation between the chromosome number and the PI.
      These results suggest a serious degradation of the ecosystem due to the
      wastewaters with a direct impact on its inhabitants.

PMID- 16626807
TI  - Breaking up the tie: disintegrin-like metalloproteinases as regulators of cell
      migration in inflammation and invasion.
AB  - Cell adhesion and cell migration are essential for a variety of important events
      in both embryonic development and in the adult organism. Cell adhesion molecules
      (CAM) like selectins, immunoglobulin superfamily members, integrins, and
      cadherins undergo diverse mechanisms of regulation. Dysregulation of adhesion can
      lead to pathological processes, including inflammatory diseases or tumor
      metastasis either by disrupting the normal anchorage, thereby altering cell
      movement and regulatory signalling, or by promoting inappropriate temporal and
      spatial adhesion. An increasing body of evidence has emerged showing that members
      of the a disintegrin and metalloproteinase (ADAM) family critically contribute to
      the regulation of CAM functions. While the disintegrin domain can interact with
      integrins and mediate adhesion, the metalloproteinase domain can mediate anti
      adhesive functions by cleaving the membrane bound adhesion molecules. This
      "shedding" process leads to the release of often still functional soluble
      ectodomains and can additionally influence intracellular cell signalling
      pathways. Several soluble CAMs have been detected in vitro and in vivo. Some of
      them are strongly increased in inflammatory diseases or in the serum of cancer
      patients. Therefore the level of soluble CAMs but also the expression of the
      metalloproteinases responsible for their release might provide prognostic
      information. It could also be useful for monitoring malignant disease stages and
      for evaluating the effectiveness of various therapeutic approaches. Moreover,
      metalloproteases of the ADAM family are emerging as promising targets for new
      therapeutic options.

PMID- 16626808
TI  - Further validation of LABORAS using various dopaminergic manipulations in mice
      including MPTP-induced nigro-striatal degeneration.
AB  - The automated behavioural apparatus, LABORAS (Laboratory Animal Behaviour
      Observation, Registration and Analysis System), has been further validated with
      respect to the ability of the system to detect behavioural impairments in mice,
      following various dopaminergic manipulations. Initially data were obtained from
      mice administered with amphetamine, haloperidol, SCH23390, apomorphine and L
      DOPA, with the focus on locomotor and grooming activities. The data recorded by
      LABORAS on administration of these pharmacological tool compounds, is comparable
      with published findings using standard LMA systems and conventional observer
      methods. In addition the home cage behaviour of mice administered with the
      dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using
      an acute dosing regimen was also investigated. In LABORAS, mice subjected to MPTP
      lesioning showed deficits in spontaneous motor activity at day 6-7 post-MPTP
      administration, over a 24 h test period, as compared to saline treated controls.
      The data captured and analysed using LABORAS, suggests that the automated system
      is able to detect both pharmacologically and lesion-induced changes in behaviour
      of mice, reliably and efficiently.

PMID- 16626809
TI  - Increased dopaminergic activity in restricting-type anorexia nervosa.
AB  - Eye blink rate, a peripheral measure of central dopaminergic activity, has been
      investigated in 20 female anorexic "restricting-type" patients and 16 healthy
      female subjects. A significantly increased blink rate was found in the anorexic
      patients. A significant positive correlation between blink rate and duration of
      illness was also found.

PMID- 16626810
TI  - Stroop performance in pathological gamblers.
AB  - Pathological gambling is a relatively prevalent psychiatric disorder that
      typically leads to severe family, social, legal, and occupational problems and is
      associated with a high rate of suicide attempts. Understanding the
      neurobiological basis of pathological gambling is a current focus of research,
      and emerging data have demonstrated that pathological gamblers may have impaired
      decision-making because of an inability to inhibit irrelevant information. In
      this study, we examined pathological gamblers by using the Stroop Color-Word
      Test, a neurocognitive task used to assess interference control. The "reverse"
      variant of the Stroop Color-Word Test was administered to a cohort of medication
      free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In
      the reverse variant of the Stroop task, subjects are asked to read the meaning of
      the word rather than name the ink color. The reverse Stroop task was chosen
      because it highly discriminates ability to inhibit interference in a population
      of psychiatric patients. In our study, performance on the reverse Stroop task in
      the pathological gamblers was significantly slower and less accurate than in the
      healthy subjects. A new finding in our study was that for pathological gamblers,
      the average reaction time in the neutral condition (where the color names are
      displayed in black letters) was slower than the average reaction time in the
      incongruent condition (where the meaning of the color name and the color of the
      printed letters are different). This controlled study extends previous findings
      by showing that performance on the Stroop task is impaired in a sample of
      medication-free pathological gamblers.

PMID- 16626811
TI  - IL-6 and CCL2 levels in CSF are associated with the clinical course of MS:
      implications for their possible immunopathogenic roles.
AB  - Biological markers would provide valuable tools for tracking disease activity,
      immunopathological processes or therapeutic efficacy in MS. In this study we
      analysed a panel of Th(1)/Th(2) cytokines and the chemokine CCL2 in serum and CSF
      from MS patients and healthy controls. Increased levels of IL-6 (p<0.05) and
      decreased levels of CCL2 (p<0.001), with the lowest levels during acute relapses,
      was found in CSF from patients with relapsing-remitting MS. CSF levels of CCL2
      correlated with indices for intrathecal IgG production and the CSF level of the
      neurofilament light protein, a marker for axonal damage, indicating a
      immunopathogenic role for CCL2.

PMID- 16626812
TI  - Age increases axon loss associated with primary demyelination in cuprizone
      induced demyelination in C57BL/6 mice.
AB  - Axon loss is recognised as a significant contributor to the progression of the
      disability associated with multiple sclerosis. Although evidence of axon damage
      is found in areas of chronic demyelination it is more frequently seen in
      association with acute demyelination. This study compares the incidence of axon
      degeneration associated with the areas undergoing demyelination in young adult (8
      10 weeks) and aged (6-7 months) C57BL/6 mice in cuprizone intoxication; a widely
      used model of demyelination. The incidence of axon transection, as indicated by
      the presence of SMI 32 positive axonal spheroids, and evidence of axon loss in
      the medial corpus callosum, were significantly greater in aged mice, as was the
      magnitude of the macrophage and astrocyte response to demyelination. Aged C57BL/6
      mice are thus more prone to axon degeneration in association with demyelination
      than young adult mice. A retrospective study indicated that the incidence of axon
      degeneration was much higher in C57BL/6 mice than in the Swiss albino mice used
      in the early cuprizone intoxication studies which were fed much higher doses of
      cuprizone. These results indicate both a genetic and age susceptibility to
      demyelination-associated axon transection.

PMID- 16626813
TI  - Neuroprotection induced by mucosal tolerance is epitope-dependent: conflicting
      effects in different strains.
AB  - The ability to cope with ongoing neurodegeneration after injury to the central
      nervous system of mammals differs among strains and depends in part on the
      animal's ability to manifest a T-cell-mediated protective response. After CNS
      injury, strain-related differences were observed. Moreover, the post-injury
      effect of naturally occurring regulatory CD4+CD25+ T cells was found to differ in
      different strains. In this study, using partially injured optic nerves of
      Balb/c/OLA and C57BL/6J mice as models, we observed strain-related differences in
      the T-cell-mediated protection obtained by antigens administered via the nasal
      route. Active immunization with myelin-related antigens emulsified in complete
      Freund's adjuvant had a beneficial effect on both strains, whereas mucosal
      administration of the same antigens was destructive in mice of the Balb/c/OLA
      strain but protective in C57BL/6J mice.

PMID- 16626814
TI  - Interleukin-1 beta modulates AMPA receptor expression and phosphorylation in
      hippocampal neurons.
AB  - Interleukin (IL)-1beta is a pro-inflammatory cytokine involved in modulating
      inflammation and stress responses in the brain. Central administration of IL
      1beta impairs both memory functions and long-term potentiation (LTP) induction.
      However, the molecular events responsible for the downstream effects of IL-1beta
      are not fully understood. Given the potential regulatory role of IL-1beta in LTP,
      we assessed whether IL-1beta influences surface expression and phosphorylation of
      glutamate receptors. We found that IL-1beta, but not IL-10 or tumour necrosis
      factor (TNF)-alpha, down-regulated the surface expression and Ser831
      phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptor subunit GluR1. Agents that block IL-1beta receptor activity
      abolished these effects. In contrast, no change in the surface expression of the
      N-methyl-d-aspartate (NMDA) receptor subunit NR1 was observed. The inhibition of
      NMDA receptor activity or depletion of extracellular calcium blocked IL-1beta
      effects on GluR1 phosphorylation and surface expression. NMDA-mediated calcium
      influx was also regulated by IL-1beta. These findings suggest that IL-1beta
      selectively regulates AMPA receptor phosphorylation and surface expression
      through extracellular calcium and an unknown mechanism involving NMDA receptor
      activity.

PMID- 16626815
TI  - Anti-inflammatory properties of Type I interferons.
AB  - The notion that Type I interferons (interferon-alpha and -beta) possess anti
      inflammatory potential is supported by data from clinical application in multiple
      sclerosis, by studies on cultured immune-competent cells and by investigation of
      experimental diseases in whole animals. These observations deserve the attention
      of virologists for their potential role in the pathogenesis and clinical
      management of virus infections.

PMID- 16626816
TI  - The saposin-like proteins 1, 2, and 3 of Fasciola gigantica.
AB  - The SAP genes of Fasciola encode proteins belonging to the saposin-like protein
      family. The saposin signature, a compact domain of mainly alpha-helical
      character, contains six conserved cysteine residues and has been implicated in
      membrane-binding, pore formation, and subsequent cell lysis in several family
      members. Recombinant SAP-2 of F. hepatica has been shown to induce lysis of human
      erythrocytes and peripheral blood mononuclear cells. This suggests that the SAPs
      are involved in the nutrition of Fasciola as the released content of lysed host
      cells is available for further enzymatic processing and uptake by the parasite.
      In the present study a new SAP-3 cDNA was obtained in an immunoscreen of an adult
      stage F. gigantica cDNA library with an antiserum against the parasite's
      excretion/secretion antigens. SAP-1 and SAP-2 cDNAs were isolated from F.
      gigantica cDNA libraries using oligonucleotide primers specific to the SAP-1 and
      SAP-2 DNA sequences from F. hepatica. Transcripts of the three SAPs are present
      from the metacercarial to the adult stage and are located to the gut epithelium.
      In immatures SAP-1 RNA is the predominant product whereas in adults SAP-2 and -3
      are the more abundant products. Polyclonal anti-SAP-1 and SAP-2 antisera
      confirmed the tissue-specificity and revealed the subcellular localization of
      SAPs in large granules concentrated in the apical part of the gut epithelial
      cells of the parasite. Interestingly, evolutionary conservation of the Fasciola
      SAP sequences among other trematodes is low at 20-30% sequence identity
      comparable to the Entamoeba amoebapore sequences.

PMID- 16626817
TI  - Effects of central infusion and immunoneutralization of growth hormone on the
      timing of puberty and plasma leptin levels in the female rat.
AB  - Growth hormone (GH) levels increase during puberty though its role in puberty
      onset is still unclear. An interaction is suggested between GH and leptin, as
      triggering factor of puberty. To evaluate the role of GH on the timing of puberty
      and its relation with leptin, we centrally administered recombinant human GH
      (rhGH; 1 microg/day) to normally fed or food-restricted (FR) prepubertal female
      rats, and monitored time of vaginal opening (VO). Median time of VO was equally
      postponed in FR animals and in normally fed rhGH-infused rats: median time of VO
      was respectively 35 and 34 vs. 27 d. Central infusion of rhGH in FR rats
      partially restored the delay in VO. Plasma leptin levels were increased in rhGH
      infused animals, normally fed or FR. Centrally infused anti-rat GH (0.6
      microg/day) did not affect plasma leptin levels, but advanced median time of VO
      (25 vs. 28 d) in pair-fed female rats but not in ad lib-fed animals. The effects
      of the centrally infused compounds appear to depend on the dietary regime imposed
      on the prepubertal animals. Furthermore, plasma leptin levels show no direct or
      predictive relation to the time of VO. The data indicate an involvement of GH in
      puberty onset, but do not explain the mechanism employed.

PMID- 16626818
TI  - Role of the Cys18-Cys274 disulfide bond and of the third extracellular loop in
      the constitutive activation and internalization of angiotensin II type 1
      receptor.
AB  - An insertion of residues in the third extracellular loop and a disulfide bond
      linking this loop to the N-terminal domain were identified in a structural model
      of a G-protein coupled receptor specific to angiotensin II (AT1 receptor), built
      in homology to the seven-transmembrane-helix bundle of rhodopsin. Both the
      insertion and the disulfide bond were located close to an extracellular locus,
      flanked by the second extracellular loop (EC-2), the third extracellular loop (EC
      3) and the N-terminal domain of the receptor; they contained residues identified
      by mutagenesis studies to bind the angiotensin II N-terminal segment (residues D1
      and R2). It was postulated that the insertion and the disulfide bond, also found
      in other receptors such as those for bradykinin, endothelin, purine and other
      ligands, might play a role in regulating the function of the AT1 receptor. This
      possibility was investigated by assaying AT1 forms devoid of the insertion and
      with mutations to Ser on both positions of Cys residues forming the disulfide
      bond. Binding and activation experiments showed that abolition of this bond led
      to constitutive activation, decay of agonist binding and receptor activation
      levels. Furthermore, the receptors thus mutated were translocated to cytosolic
      environments including those in the nucleus. The receptor form with full deletion
      of the EC-3 loop residue insertion, displayed a wild type receptor behavior.

PMID- 16626819
TI  - Serum tryptase levels and Kounis syndrome.

PMID- 16626820
TI  - Doppler echocardiography during the follow-up of hematological patients
      undergoing chemotherapy.
AB  - Our retrospective experience underscores the ability of Doppler echocardiography
      to detect the cardiotoxicity of chemotherapy (functional and pericardial
      abnormalities, heart involvement) and points out the need for an accurate
      echocardiographic follow-up of hematologic patients.

PMID- 16626821
TI  - "Iodide mumps" after coronary angioplasty.

PMID- 16626822
TI  - A huge obstructive myxoma located in the right heart without causing any symptom.
AB  - Cardiac myxoma is unusual and mostly located in left atrium. Although it is a
      benign tumor of the heart, it may cause life-threatening cardiac problems like
      valvular obstruction, systemic or pulmonary massive embolism, infection,
      arrhythmia, malignance. We report a huge cardiac myxoma originated from right
      atrium. It was moving between right atrium and ventricle without any symptoms.

PMID- 16626823
TI  - Development of a lab-made microarray for analyzing the genetic diversity of
      nitrogen fixing symbionts Sinorhizobium meliloti and Sinorhizobium medicae.
AB  - Some bacterial species, like nitrogen-fixing Sinorhizobium that interact with
      Medicago plants, are prone to frequent horizontal gene transfers. Investigation
      of their genetic structure requires to study polymorphism patterns at many loci.
      Although DNA microarrays represent a method of choice for high throughput
      analysis of polymorphisms, this technology yet remains an expensive and heavy
      approach, thus depriving most of research groups from this powerful tool. In an
      attempt to overcome this limitation, we have developed a simple genotyping
      procedure by DNA microarrays, and have evaluated its ability to characterize a
      Sinorhizobium population. Thirty 18- to 24-mer oligonucleotide probes were
      designed to target the most frequent mutations in three polymorphic loci of
      Sinorhizobium meliloti and S. medicae. Probe hybridization efficiency was
      compared on two spotting surfaces: nylon membranes and epoxy-coated glass slides.
      Epoxy-coated glass slides revealed more sensitive than nylon membranes and
      allowed discrimination of single mismatches. Using this procedure, an
      uncharacterized population consisting of 33 S. meliloti/S. medicae isolates was
      successfully genotyped.

PMID- 16626824
TI  - rpoB gene: a target for identification of LAB cocci by PCR-DGGE and melting
      curves analyses in real time PCR.
AB  - Lactic acid bacteria (LAB) are essential in the quality of many fermented
      beverages like beer, cider and wine. In the two later cases, they convert malic
      acid into lactic acid during the malolactic fermentation. After fermentation,
      microbial stabilization is needed to prevent the development of spoilage bacteria
      species. Among them, cocci lead to different alterations: Pediococcus sp., and
      some strains of Leuconostoc mesenteroides and Oenococcus oeni can produce
      exopolysaccharides which modify wine viscosity and lead to ropiness. They also
      can produce acetic acid, biogenic amine, ethyl carbamate and volatile phenols.
      Therefore detection and identification are crucial. Results of phenotypic tests
      and DNA-DNA probes are not accurate enough. 16S RNA gene which is currently used
      for bacterial species identification presents intraspecies heterogeneity. The
      rpoB gene is an alternative to this limitation. However previous PCR targeting
      partial sequence of rpoB gene could not delimit cocci species. Therefore we
      compared the rpoB gene sequence of the six main cocci species found in fermented
      beverages: P. damnosus, P. dextrinicus, P. parvulus, P. pentosaceus, L.
      mesenteroides and O. oeni. The most discriminating partial sequence of the rpoB
      gene was chosen for designing primers. By PCR-DGGE the reliability of these
      primers was verified. It was controlled in a mixture of several cocci and other
      lactic acid bacteria (Lactobacillus sp.). Then we adapted the primers and the PCR
      conditions in order to achieve the identification of cocci species by real time
      PCR program including the fluorescent dye SYBR Green I, which gives faster
      results. PCR melt curves were established and a specific T(m) was attributed to
      each species.

PMID- 16626825
TI  - AFLP fingerprinting of Colombian Clostridium spp strains, multivariate data
      analysis and its taxonomical implications.
AB  - Amplified Fragment Length Polymorphism (AFLP) analysis was used for
      characterising 13 native Colombian Clostridium spp strains. The DNA extraction
      method was optimised and the use of cetyl trimethyl ammonium bromide (CTAB) and
      sodium chloride (NaCl) was incorporated. All strains could be typed in these
      conditions. The AFLP profiles obtained were submitted to multivariate analysis
      and compared with previous pulsed field gel electrophoresis (PFGE) results. The
      results suggested that the set of native strains could correspond to two new
      species different to those having been described to date. It is proposed that DNA
      DNA hybridisation analysis should be done to produce complementary information
      for describing the new species.

PMID- 16626826
TI  - A phase II study of concomitant boost radiation plus concurrent weekly cisplatin
      for locally advanced unresectable head and neck carcinomas.
AB  - BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity
      of weekly cisplatin along with concomitant boost accelerated radiation regimen in
      patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND
      METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n =
      19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity
      were included. Patients received radiotherapy with a concomitant boost scheme
      (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy)
      and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most
      patients (95%) received both radiation and chemotherapy according to protocol.
      Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal
      toxicity in 85 and 50% of patients, respectively. Haematological toxicity was
      mild. Four patients (4%) died due to complications. With a median follow of 41
      months, median overall survival and time to progression were 27 and 25 months,
      respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS:
      Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a
      feasible schedule in patients with locally advanced unresectable head and neck
      carcinoma, with acceptable toxicity and survival data.

PMID- 16626827
TI  - Staging of nasopharyngeal carcinoma investigated by magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: To investigate the American Joint Commission on Cancer
      (AJCC) sixth edition staging system of nasopharyngeal carcinoma (NPC) by Magnetic
      Resonance Imaging (MRI). PATIENTS AND METHODS: One hundred and fifty-nine non
      disseminated biopsy-proven NPC patients were studied with MRI before treatment.
      Retrieval of MRI information enabled us to restage all patients accurately
      according to the sixth edition of the AJCC staging system. Splitting the
      respective T and N stages by the significant defining factors identified, the
      cancer death hazard ratios were modeled by the Cox model in SPSS 10.0 for windows
      (SPSS Inc, Chicago, IL). RESULTS: Single site of skull base abnormality (HR =
      3.91, 95% CI: 0.74-20.56) has a superior result to others involved in T3 (HR =
      5.83, 95% CI: 1.24-27.29). Involvement of either anterior or posterior cranial
      nerves solely (HR = 6.02, 95% CI: 1.55-35.60) was not found to be as a poor
      prognostic indicator as others involved in T4 (HR = 7.81, 95% CI: 1.81-33.63).
      Less than or equal to 3 cm of N1 (HR = 4.01, 95% CI: 0.48-33.83) and N2 (HR =
      4.72, 95% CI: 0.62-35.78) have a better result than >3 cm of N1 (HR = 8.09, 95%
      CI: 0.95-68.97) and N2 (HR = 10.58, 95% CI: 1.32-84.62), respectively.
      CONCLUSIONS: Perhaps, it is better to down-stage single site of skull base
      abnormality from T3 to T2, and involvement of either anterior or posterior
      cranial nerves solely from T4 to T3, meanwhile, < or =3 cm of N2 down-stage to
      N1, >3 cm of N1 up-stage to N2.

PMID- 16626829
TI  - Dose-response relationship of nasopharyngeal carcinoma above conventional
      tumoricidal level: a study by the Hong Kong nasopharyngeal carcinoma study group
      (HKNPCSG).
AB  - BACKGROUND AND PURPOSE: To define the dose-response relationship of
      nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of
      66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique.
      PATIENTS AND METHODS: Data from all five regional cancer centers in Hong Kong
      were pooled for this retrospective study. All patients (n = 2426) were treated
      with curative-intent RT with or without chemotherapy between 1996 and 2000 with
      the basic RT course using the Ho's technique. The primary endpoint was local
      control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T
      stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years)
      was studied. Both univariate and multivariate analyses were performed. RESULTS:
      On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal
      boost (P = 0.01; HR, 0.34) were the only significant factors affecting local
      failure for the whole study population, and for the population of patients
      treated by radiotherapy alone, but not for patients who also received
      chemotherapy. The following were independent determinants of local failure for
      patient groups with different T-stages treated by radiotherapy alone: use of a
      boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60)
      and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors
      treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a
      lower local failure rate than a 10 Gy-boost. There was no apparent excess
      mortality attributed to RT complications. CONCLUSIONS: Within the context of a
      multi-center retrospective study, dose-escalation above 66 Gy significantly
      improved local control for T1/T2a and T3/4 tumors when the primary RT course was
      based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC
      warrants further investigation. Caution should be taken when boosting is
      considered because of possible increase in radiation toxicity.

PMID- 16626831
TI  - The cognit: a network model of cortical representation.
AB  - The prevalent concept in modular models is that there are discrete cortical
      domains dedicated more or less exclusively to such cognitive functions as visual
      discrimination, language, spatial attention, face recognition, motor programming,
      memory retrieval, and working memory. Most of these models have failed or
      languished for lack of conclusive evidence. In their stead, network models are
      emerging as more suitable and productive alternatives. Network models are
      predicated on the basic tenet that cognitive representations consist of widely
      distributed networks of cortical neurons. Cognitive functions, namely perception,
      attention, memory, language, and intelligence, consist of neural transactions
      within and between these networks. The present model postulates that memory and
      knowledge are represented by distributed, interactive, and overlapping networks
      of neurons in association cortex. Such networks, named cognits, constitute the
      basic units of memory or knowledge. The association cortex of posterior-post
      rolandic-regions contains perceptual cognits: cognitive networks made of neurons
      associated by information acquired through the senses. Conversely, frontal
      association cortex contains executive cognits, made of neurons associated by
      information related to action. In both posterior and frontal cortex, cognits are
      hierarchically organized. At the bottom of that organization-that is, in
      parasensory and premotor cortex-cognits are small and relatively simple,
      representing simple percepts or motor acts. At the top of the organization-in
      temporo-parietal and prefrontal cortex-cognits are wider and represent complex
      and abstract information of perceptual or executive character. Posterior and
      frontal networks are associated by long reciprocal cortico-cortical connections.
      These connections support the dynamics of the perception-action cycle in
      sequential behavior, speech, and reasoning.

PMID- 16626832
TI  - Antimicrobial resistance in Irish isolates of verocytotoxigenic Escherichia coli
      (E. coli)--VTEC.
AB  - This study compared the antimicrobial resistance profiles of Escherichia coli
      O157:H7 isolates (n=257) recovered from bovine hides, minced beef and human
      clinical samples in Ireland, to those profiles of a range of Irish non-O157 E.
      coli (O111 and O26) isolates (n=31) from a variety of clinical and veterinary
      sources. Four multi-drug resistant (MDR) E. coli O157:H7 food isolates were
      identified, with resistance to 10 (1 isolate), 6 (1 isolate) and 4 (2 isolates)
      antimicrobial agents, respectively. Two of these isolates (resistant to 7 and 4
      antimicrobial classes) were characterised further by molecular methods and found
      to contain class 1 integrons along with a beta-lactamase-encoding tem-1 gene.
      Transfer of antimicrobial resistance (ampicillin, streptomycin and
      sulphonamides), the tem-1 gene and markers (int1, qacEDelta1, sul1)
      characteristic of class 1 integrons were evident in one MDR isolate (resistant to
      4 antimicrobial classes) when conjugation and transformation experiments were
      performed. A clinical isolate and a veterinary isolate of the O111 serotype were
      MDR and resistant to 4 and 3 antimicrobial classes, respectively. These data
      suggest that the prevalence of antimicrobial resistance among the three VTEC
      serotypes examined in this study is low. However, these organisms may become a
      public health risk should they enter the food chain.

PMID- 16626833
TI  - Yeasts isolated from three varieties of grapes cultivated in different locations
      of the Dolenjska vine-growing region, Slovenia.
AB  - The number and diversity of yeasts on grape berry surfaces are influenced by
      several factors, such as grape variety, degree of grape maturity at harvest,
      climatological conditions, geographic location, physical damage of grapes, the
      intensity of pest management etc. Cvicek is a typical Slovene wine, which has
      obtained a special protection under the Slovene Wine Law for its geographical
      origin. This blended red wine is produced from different grape varieties (Vitis
      vinifera L.), mostly from red grapes of Zametovka and Modra frankinja and from
      white grapes of Kraljevina. The aim of this study was to evaluate the impact of
      geographical locations in the Dolenjska vine-growing region and to obtain precise
      information about the influence of different grape varieties on the composition
      of yeast community on grape berries. The restriction fragment length polymorphism
      of PCR-amplified fragments from the rDNA gene cluster (PCR RFLP of rDNA) has been
      used for the differentiation of yeast species. The standard identification
      procedure has been performed on representative strains that shared identical RFLP
      profiles. The number of yeasts and yeast species isolated varied according to
      different grape varieties, Zametovka, Modra frankinja and Kraljevina (V. vinifera
      L.) and according to different sampling location. On the surface of grape berries
      13 different yeast species have been identified. Saccharomyces cerevisiae has not
      been found.

PMID- 16626834
TI  - Second stage production of iturin A by induced germination of Bacillus subtilis
      RB14.
AB  - Bacillus subtilis RB14, a dual producer of lipopeptide antibiotics iturin A and
      surfactin undergoes sporulation in the submerged fermentation and the production
      of these secondary metabolites becomes halted. In this study, production of
      lipopeptide antibiotics was investigated by induced germination of the spores by
      heat-activation and nutrient supplementation. The induced spores became
      metabolically active vegetative state and produced lipopeptide antibiotic iturin
      A that added up the total production at the end of the fermentation. However,
      additional production of surfactin was not observed. This second time iturin A
      production by the germinated cells from the spores was defined as second stage
      production.

PMID- 16626835
TI  - In-vivo efficacy of novel paclitaxel nanoparticles in paclitaxel-resistant human
      colorectal tumors.
AB  - Colloidal carriers have been shown to improve tumor therapy by increased drug
      delivery into tumor sites resulting directly from the enhanced permeability and
      retention effect (EPR). However, the clinical outcome of tumor therapy is often
      limited due to multidrug resistance. Several different types of resistance exist
      with expression of p-glycoprotein being the most commonly described. Paclitaxel
      entrapped in emulsifying wax nanoparticles (PX NPs) was shown to overcome drug
      resistance in a human colon adenocarcinoma cell line (HCT-15). In the present
      studies, the in-vivo efficacy of PX NPs in a HCT-15 mouse xenograft model was
      demonstrated. Significant inhibition in tumor growth was observed in mice
      receiving PX NPs treatment. Additionally, mice dosed with Taxol also demonstrated
      slower tumor growth; however, the efficacy of the Taxol treatment was shown in
      the in-vitro HUVEC model to be due to the antiangiogenic effect of paclitaxel. It
      was concluded that the enhanced efficacy of PX NPs over Taxol in the xenograft
      model was due to both overcoming paclitaxel resistance and an antiangiogenic
      effect.

PMID- 16626836
TI  - Mechanism of fluid infusion during microneedle insertion and retraction.
AB  - Previous work has shown that infusion flow rates can be increased by an order of
      magnitude by partially retracting microneedles after insertion into the skin.
      This study sought to determine the mechanism by which retraction increases fluid
      infusion by piercing human cadaver skin with single microneedles, fixing the skin
      after retracting microneedles to different distances, and examining skin
      microstructure by histology. We found that microneedle insertion to 1080 microm
      from the skin surface resulted primarily in skin indentation and only 100-300
      microm penetration into the skin. This caused significant compaction of the skin,
      which probably pressed out most water and thereby dramatically lowered the flow
      conductivity of skin beneath the needle tip. Retraction of the microneedle
      allowed the skin to recoil back toward its original position, which relieved the
      skin compaction and increased local flow conductivity. Altogether, these results
      suggest that microneedle insertion to penetrate into the skin followed by
      microneedle retraction to relieve skin compaction is an effective approach to
      infuse fluid into the skin in a minimally invasive manner.

PMID- 16626837
TI  - Pathophysiology and treatment of pain in joint disease.
AB  - Deep somatic pain originating in joints and tendons is a major therapeutic
      challenge. Spontaneous pain and mechanical hypersensitivity can develop as a
      consequence of sensitization of primary afferents directly involved in the
      inflammatory process, but also following sensitization of neuronal processing in
      the spinal cord (central sensitization) or higher centres. Inflammatory pain is
      linked to sensitization of sensory proteins at the nociceptive endings whereas
      pain originating from nerve damage (neuropathic pain) has been linked to changes
      in axonal ion channels producing ectopic discharge in nociceptors as a source of
      pain. New targets for analgesic therapy include sensory proteins at the
      nociceptive nerve endings such as the activating TRPV and ASIC channels, but also
      inhibitory opioid and cannabinoid receptors. Therapeutic targets are also found
      among the axonal channels that set membrane potential and modulate discharge
      frequency such as voltage sensitive sodium channels and various potassium
      channels.

PMID- 16626838
TI  - 'Finish your soup': counterproductive effects of pressuring children to eat on
      intake and affect.
AB  - The authors examined whether pressuring preschoolers to eat would affect food
      intake and preferences, using a repeated-measures experimental design. In the
      experimental condition, children were pressured to eat by a request to finish
      their food. We collected intake data, heights and weights, child-feeding
      practices data, and children's comments about the food. Children consumed
      significantly more food when they were not pressured to eat and they made
      overwhelmingly fewer negative comments. Children who were pressured to eat at
      home had lower body mass index percentile scores and were less affected by the
      pressure in the lab setting than children who were not pressured at home. These
      data provide experimental evidence supporting previous correlational research
      indicating that pressure can have negative effects on children's affective
      responses to and intake of healthy foods.

PMID- 16626839
TI  - Sex difference in body weight gain and leptin signaling in hypocretin/orexin
      deficient mouse models.
AB  - Recent studies in human and animal models of narcolepsy have suggested that
      obesity in narcolepsy may be due to deficiency of hypocretin signaling, and is
      also under the influence of environmental factors and the genetic background. In
      the current study, using two hypocretin/orexin deficient narcoleptic mouse models
      (i.e. preproorexin knockout (KO) and orexin/ataxin-3 transgenic (TG) mice) with
      cross-sectional assessments, we have further analyzed factors affecting obesity.
      We found that both KO and TG narcoleptic mice with mixed genetic backgrounds (N4
      5, 93.75-96.88% genetic composition of C57BL/6) tended to be heavier than wild
      type (WT) mice of 100-200 days old. The body weight of heterozygous mice was
      intermediate between those of KO and WT mice. Obesity was more prominent in
      females in both KO and TG narcoleptic mice and was associated with higher serum
      leptin levels, suggesting a partial leptin resistance. Obesity is less prominent
      in the congenic TG narcoleptic mice, but is still evident in females. Our results
      confirmed that hypocretin/orexin ligand deficiency is one of the critical factors
      for the obese tendency in narcolepsy. However, multiple factors are also likely
      to affect this phenotype, and a sex difference specific alteration of leptin
      hypocretin signaling may be involved.

PMID- 16626840
TI  - Heterocyclic analogs of benzanilide derivatives as potassium channel activators.
      IX.
AB  - On the basis of our previous works, addressed to synthesise new activators of BK
      potassium channels, and of many suggestions from the international literature, a
      simple pharmacophoric model, consisting of two suitably substituted phenyl rings
      bound to various kinds of linkers, was hypothesised. In particular, the
      effectiveness of the amidic linker was demonstrated, since several benzanilide
      derivatives showed interesting BK-opener properties. As a development of these
      benzanilides, in this work we introduced heterocyclic substituents, replacing the
      aryl ring on the acid side or on the basic one of the amide linker of the above
      pharmacophore. The pharmacological results indicated some relevant remarks about
      the structural requirements, needed for a satisfactory BK-opener activity. In
      particular, the presence of a phenolic function, with a possible H-bond donor
      role, has been confirmed. Furthermore, the presence of nitrogen heterocycles on
      the acid side of the amide linker seems to be a negative requirement, while furan
      and thiophene were well tolerated. On the contrary, the introduction of
      insaturated heterocyclic rings (pyridine and thiazole) on the basic side of the
      amide linker, led to satisfactory biological activity, while the presence of
      aliphatic heterocycles lowered the pharmacological effect.

PMID- 16626841
TI  - Plasma levels of brain derived-neurotrophic factor and catecholamine metabolites
      are increased during active phase of psychotic symptoms in CNS lupus: a case
      report.
AB  - In the present study, the authors reported a case of systemic lupus erythematosus
      (SLE) with central nervous system involvement (CNS lupus). The authors also
      longitudinally investigated plasma levels of brain-derived neurotrophic factor
      (BDNF) and catecholamine metabolites in the patient, and found that plasma levels
      of BDNF, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were
      raised in accordance with the severity of psychotic symptoms in this case of CNS
      lupus. These results suggest that it is useful to measure plasma levels of BDNF
      and the catecholamine metabolites in order to predict the severity of psychotic
      symptoms in CNS lupus and to provide a differential diagnosis from that of
      steroid-induced psychosis.

PMID- 16626842
TI  - Comments on "Paradoxial rate-dependent effect of fluoxetine on captivity-induced
      stereotypies in bank voles" by Lieve Meers, Frank Olof Odberg. In: Progress in
      Neuro-Psychopharmacology and Biological Psychiatry 29 (2005) 964-971.

PMID- 16626843
TI  - Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism and mood
      disorders: a preliminary study.
AB  - This study examined the relationship between a MnSOD gene (MnSOD) polymorphism
      (Ala-9Val) and mood disorders such as major depressive disorder (MDD) and bipolar
      I disorder (BD). Eighty patients with BD, 61 patients with MDD and 106 healthy
      controls were enrolled in this study and genotyped using a polymerase chain
      reaction-based method. The patients with MDD and BD, and the controls had a
      similar distribution of the genotypes and alleles in the Ala-9Val MnSOD
      polymorphism. The combined analysis (MDD plus BD) also failed to find any
      association between the Ala-9Val MnSOD polymorphism and mood disorders. Subgroup
      analyses according to the clinical variables such as the family history, age at
      onset, psychotic features and suicide history failed to identify any association
      with the Ala-9Val MnSOD polymorphism. This preliminary data suggests that at
      least in the Korean population, the Ala-9Val MnSOD polymorphism is not associated
      with the development of mood disorders or their clinical parameters. However,
      more study with a larger population sample will be needed.

PMID- 16626844
TI  - Activity of common anticonvulsant drugs on spinal seizure-induced by sudden
      cooling.
AB  - Although some of the clinical signs associated with epilepsy have their origin in
      supraspinal structures, it is the spinal cord in the end, which is responsible
      for generating the typical pattern of tonic-clonic contractions associated with a
      convulsion. Indeed, the spinal cord isolated from influence of the brain is
      capable of convulsive and paroxysmal activity that exhibits the same stereotyped
      motor pattern seen in the intact animal. This motor pattern can be reproduced
      experimentally by cooling the isolated spinal cord of amphibians. The isolated
      spinal cord-hindleg preparation of toad was used. Convulsive activity was induced
      by placing the isolated spinal cord into a Ringer's bath kept at 7 degrees C. The
      characteristic phases of the convulsion and their intensity were assessed by
      recording tonic-clonic contractions of hindleg muscles. Two main endpoints were
      used to assess the anticonvulsive activity of the drugs tested: first, their
      ability to block only the tonic hind-limb extension (THE) and second, their
      ability to block all tonic-clonic activity. The ED50 values and its 95%
      confidence interval estimated for abolition of THE for each drugs was (mg/kg):
      carbamazepine 8.6 (6.8-10.8), phenytoin 13 (7.1-23.6), diazepam 0.007 (0.004
      0.01), MK-801 3.4 (2.0-5.7), valproate 120 (40-400), phenobarbital 17.1 (12.2
      23.9), pentobarbital 10 (6-16.4), mephenesin 2-5 and acetazolamide >500. The
      ability of some of these drugs to inhibit this kind of seizure activity at doses
      within therapeutic range suggests a potential use of this isolated preparation as
      a model in the study and testing of new anticonvulsive drugs.

PMID- 16626845
TI  - Ketamine administration disturbs behavioural and distributed neural correlates of
      fear conditioning in the rat.
AB  - The neurotransmitter glutamate and its associated receptors perform an important
      role in the brain circuitry underlying normal fear processing. The glutamate NMDA
      receptor, in particular, is necessary for the acquisition and recollection of
      conditioned-fear responses. Here the authors examine how acute blockage of the
      NMDA receptor with sub-anaesthetic doses of ketamine affects behavioural assays
      of fear-conditioned stress (e.g. freezing) and cFos expression in a network of
      brain areas that have previously been implicated in fear processing. Fear
      conditioned rats displayed significantly more freezing behaviour than non
      conditioned controls. In fear-conditioned rats that also received ketamine, this
      conditioning effect was largely neutralised. Fear conditioning also led to
      increased cFos expression in various areas central to fear processing, including
      the basolateral nucleus of the amygdala, the paraventricular nucleus of the
      hypothalamus and the anterior cingulate. Ketamine abolished such increases in
      cFos expression in most brain areas investigated. The present study therefore
      demonstrates that systemic ketamine administration in rats interferes with fear
      conditioning on a behavioural level and in a network of brain regions associated
      with fear and anxiety. The combination of ketamine and fear conditioning may
      therefore provide a useful model of abnormal fear processing, as observed in
      certain psychiatric conditions.

PMID- 16626846
TI  - Monoamine and motor responses to cocaine are co-deficient in the Fawn-Hooded
      depressed animal model.
AB  - The Fawn-Hooded (FH) genetic animal model of depression continues to be of
      interest because the FH model has limited biochemical and immune function. The FH
      animal has an inherited trait, platelet storage pool deficiency (PSPD), an
      hemorrhagic disorder that is also a component of Chediak-Higashi syndrome (CHS).
      CHS is a pyrogenic infectious childhood disease; few patients live past the age
      of 20. Our hypothesis was that FH animals may exhibit different monoamine and
      motor responses to cocaine versus the Sprague-Dawley (SD) "normal" animal strain,
      which does not have the FH trait. Therefore, selective neuromolecular imaging
      (NMI) of the monoamines, dopamine (DA) and 5-HT within nucleus accumbens (NAcc)
      of behaving male FH versus SD rats was performed in vivo with BRODERICK PROBE
      sensors and a semiderivative voltammetric circuit. Each animal was placed in a
      faraday chamber and electrochemical signals were detected via a mercury
      commutator and flexible cable. Baseline values for neurotransmitters and behavior
      were derived during the last half-hour of habituation behavior. Release of DA and
      5-HT was detected selectively, at separate oxidation potentials, within seconds,
      before and after intraperitoneal administration of the psychostimulant, cocaine
      (10 mg/kg). At the same time, frequencies of ambulations and central ambulations
      were separately monitored with infrared photobeams, which surrounded the faraday
      chamber. Data were compared by ANOVA analysis followed by Tukey's post hoc test.
      The data showed that (1) DA release in NAcc of behaving FH animals did not
      respond to cocaine; neither first hour nor second hour values significantly
      differed from baseline (both hours, p>0.05), whereas SD animals exhibited a
      significant increase in cocaine-induced DA release in NAcc (both hours, p<0.001).
      The ability for acute cocaine to increase DA release in NAcc was significantly
      greater in SD than in FH animals (p<0.001). (2) 5-HT release in NAcc of behaving
      FH animals was not significantly increased by cocaine (both hours, p>0.05),
      whereas 5-HT release in NAcc of SD animals was significantly increased after
      cocaine (both hours, p<0.001). The ability for acute cocaine to increase 5-HT
      release was significantly greater in SD than in FH animals (p<0.001). (3)
      Ambulations in the FH strain were modestly, yet significantly, enhanced after
      cocaine during both hours of study (p<0.05, p<0.001, respectively) as were
      ambulations in the SD strain. Nonetheless, the ability for acute cocaine to
      increase ambulations was significantly greater in SD than in FH animals in the
      first hour (p<0.001). (4) Central ambulations in the FH strain was not affected
      by cocaine (both hours, p>0.05), whereas SD animals showed a significant increase
      in central ambulatory activity in both hours of the cocaine study (p<0.001). The
      ability for acute cocaine to increase central ambulations was significantly
      greater in SD than in FH animals (p<0.001). Thus, this is the first study to
      determine in vivo the neurochemical response to acute cocaine in the behaving FH
      animal. Moreover, this is the first study to determine in vivo and simultaneously
      the neurochemical and behavioral response to acute cocaine in the FH strain in
      comparison with SD animals, a "normal" strain. Remarkable deficiencies in the
      ability for acute cocaine to alter neurochemistry and behavior in animals with
      the FH trait are shown. These studies emphasize the need to look differentially
      at cocaine effects in biochemically and immune-compromised subjects versus
      "normal" subjects.

PMID- 16626847
TI  - March 27, 1827 and what happened later--the impact of psychiatry on evolutionary
      theory.
AB  - In the interaction between Psychiatry and evolutionary theory the force of the
      impact has not always been in one direction. The Brownes, father and son, had an
      influence on the development of Darwin's theory at different points in the
      nineteenth century. The crystallization by Miskolczy in 1933 of the concept that
      schizophrenia is a disorder that is specific to Homo sapiens is another example.
      In 1964 the formulation of the central paradox of psychosis by Huxley, Mayr and
      co-authors and the subsequent critique by Kuttner et al. of the solution Huxley
      et al. had offered opened up evolutionary approaches to aetiology. Here it is
      argued that a resolution of this paradox requires identification of the
      speciation event for modern H. sapiens and elucidation of its neuroanatomical and
      physiological consequences. It necessitates a saltational account of species
      transitions and the recognition of species-specific genetic variation. Pursuit of
      these objectives leads to the hypothesis that speciation events occur selectively
      on the heterogametic chromosome (the Y in mammals) and are followed by a phase of
      sexual selection to establish a new specific mate recognition system. In H.
      sapiens the core component of this system is the capacity for language; the
      nuclear symptoms of schizophrenia are necessary clues to its neural structure.

PMID- 16626848
TI  - [Salvage of digits replantations by direct arterial antithrombotic infusion].
AB  - At the end of the seventy, we saw the reconstructive microsurgery developed to
      such an extent that it became a new and an independent surgical specialty. The
      development of the microsurgical instrumentation and the description of the
      surgical anatomy allowed the application of this technology to the most complex
      plastic reconstructions and particularly to the replantation of the amputated
      digits, especially the very distal digital amputations. Nowadays, the indications
      of digital replantation are well-defined according to numerous parameters
      conditioning the anatomical result and the functional outcome. It is well-known
      that the replantation of the amputated digit should be realized as soon as
      possible with optimal conditions of digital hibernation during the patient
      transport. In spite of that technical progress, the failure rate is still
      relatively important. The causes are sometimes recognizable and connected to
      technical defection, such as a non permeable vascular anastomosis, bad
      hemodynamics conditions or an insufficient anticoagulation, while in certain
      cases, the digital ischemia occurs in spite of permeable and technically
      successful arterial anastomosis. We then consider a "no reflow phenomenon". It
      corresponds to the constitution of vascular microthrombi which will block the
      arteriolar network. Those microthrombi are inaccessible to the microsurgical
      techniques and their treatment remains medical by intra-arterial infusion of
      antithrombotic agents. Through our series of fifteen digital replantations,
      having suffered a "no reflow phenomenon", we are going to present the
      fibrinolytic protocol we used and the promising results we obtained. All our
      patients were victims of traumatisms associating avulsions and crush injuries
      mechanisms. The conditions of preservation of the amputated digits were all quite
      unfavourable: 1) the amputated digit soaked in water in 5 cases; 2) the amputated
      fingers underwent a long-term "warm ischemia" in three cases, going up to 13
      hours for one of them; 3) the amputated digits were completely frozen in six
      cases; 4) and one amputated finger was correctly hibernated but for too long a
      period (8 hours). The signs of ischemia appeared very prematurely in the first
      minutes after the microvascular revascularisation in ten cases, and in average
      within three hours postoperatively in the other five cases, with extreme cases
      going from 2 up to 6 hours. As soon as the diagnosis of "no reflow phenomenon"
      was confirmed, an intra-arterial catheter was fixed. The radial axis was chosen
      as the arterial infusion way and approached at the level of the pulse groove. The
      antithrombotic protocol included a flash of 50,000 UI of urokinase, 36 ml of
      lidocaine 1% and 40 mg of enoxaparine, followed by an electric syringe infusion
      the first six hours with 150,000 UI of urokinase, 36 ml of lidocaine 1% and 40 mg
      of enoxaparine at 6 cc/h speed. The urokinase was then interrupted but the intra
      arterial infusion maintained with 72 ml of lidocaine 1% and 80 mg of enoxaparine
      for 24 hours, at a 3 cc/h speed, and this for ten days. In 12 cases, the "no
      reflow phenomenon" was able to be raised and the digital vascularization
      restored. The success rate is very encouraging (80%) and it turns this protocol
      into a precious ally of the digit replantation microsurgery and an effective
      therapeutic means way against the "no reflow phenomenon".

PMID- 16626849
TI  - [Surgical treatment of male-to-female transsexuals: a ten-year experience
      assessment].
AB  - From May 1995 to March 2005 sixty-three consecutive male-to-female gender
      transformation surgeries were performed at our university center by one author.
      Our retrospective study collected data from medical records, questionnaire and
      physical examination. Fifty-nine percent of patients had autologous blood
      transfusion. Histological examination of testicles found beginning cancer in 1
      case. After a-8-year initial period where secondary bilateral Z-plasties were
      systematically performed, this procedure was abandoned because it left unnatural
      visible scars. Excluding haematomas (9 cases), we found 8 major complications
      (12,6%): 1 rectal lesion, 1 leg compression, 5 skin necrosis of the vaginoplasty
      (total necrosis in 2 cases, partial necrosis in 2 cases, necrosis of full
      thickness skin graft in 1 case), and 1 secondary post-traumatic rectovaginal
      fistula. The questionnaire was completed by 22 patients with a-45-month mean
      follow-up. Results were graded on a 0 to 10 scale. Mean grades were global
      satisfaction: 7.6, life quality: 8.4, genitalia appearance: 8.0, clitoris
      sensitivity: 8.4, urinary function: 8.3, vaginal function: 7.2, sexual function:
      7.0. Rate of general satisfaction was high. In a few cases however, patients
      expressed some disappointment both in being considered as women in their daily
      living and in having sexual intercourse. These poor results seem clearly related
      to unfavourable anatomical and morphological initial conditions. Our series
      demonstrates that surgical treatment of psychiatric disorders meets physical
      limitations.

PMID- 16626850
TI  - A material decoy of biological media based on chitosan physical hydrogels:
      application to cartilage tissue engineering.
AB  - The cartilage tissue has a limited self-regenerative capacity. Tissue-engineering
      represents a promising trend for cartilage repair. The present study was aimed to
      develop a biomaterial formulation by combining fragments of chitosan hydrogel
      with isolated rabbit or human chondrocytes. We first reported the properties of
      the constructs elaborated with rabbit chondrocytes and pure chitosan physical
      hydrogels with defined molecular weight, acetylation degree and polymer
      concentration. Morphological data showed that chondrocytes were not penetrating
      the hydrogels but tightly bound to the surface of the fragments and spontaneously
      formed aggregates of combined cell/chitosan. A significant amount of neo-formed
      cartilage-like extracellular matrix (ECM) was first accumulated in-between cells
      and hydrogel fragments and furthermore was widely distributed within the neo
      construct. The optimal biological response was obtained with hydrogel fragments
      concentrated at 1.5% (w/w) of polymer made from a chitosan with a degree of
      acetylation between 30 and 40%. Such hydrogels were then mixed with human
      chondrocytes. The phenotype of the cells was analyzed by using chondrocytic (mRNA
      expression of mature type II collagen and aggrecan as well as secretion of
      proteoglycans of high molecular weight) and non chondrocytic (mRNA expression of
      immature type II collagen and type I collagen) molecular markers. As compared
      with human chondrocytes cultured without chitosan hydrogel which rapidly
      dedifferentiated in primary culture, cells mixed with chitosan rapidly loose the
      expression of type I and immature type II collagen while they expressed mature
      type II collagen and aggrecan. In these conditions, chondrocytes maintained their
      phenotype for as long as 45 days, thus forming cartilage-like nodules. Taken
      together, these data suggest that a chitosan hydrogel does not work as a
      scaffold, but could be considered as a decoy of cartilage ECM components, thus
      favoring the binding of chondrocytes to chitosan. Such a biological response
      could be described by the concept of reverse encapsulation.

PMID- 16626851
TI  - The rational designed antagonist derived from the complex structure of
      interleukin-6 and its receptor affectively blocking interleukin-6 might be a
      promising treatment in multiple myeloma.
AB  - Human interleukin-6 is involved in the maintenance and progression of several
      diseases such as multiple myeloma (MM), rheumatoid arthritis, or osteoporosis.
      Our previous work demonstrated that an interleukin-6 antagonist peptide (named
      PT) possessed potential bioactivity to antagonize the function of hIL-6 and could
      efficiently induce the growth arrest and apoptosis of XG-7 and M1 cells in a dose
      dependent manner. In this study, the theoretical interaction of the peptide PT
      with its receptor was analyzed further more with molecular docking and molecular
      dynamics methods. The theoretical studies showed that PT possessed very high
      affinity to interleukin-6R and offered a practical means of imposing long-term
      blockade of interleukin-6 activity in vivo. According to the theoretical results,
      the biological evaluation of PT was researched on two different cells models with
      more sensitive approaches: (1) The antagonist activity of PT was studied on the
      interleukin-6 dependent MM cells (XG-7) cultured with interleukin-6. In the other
      interleukin-6 dependent MM cells (SKO-007), they survived themselves by
      auto/paracrine without the exogenous interleukin-6, and also could be antagonized
      by PT. The therapeutic value of PT only limited on the interleukin-6 dependent
      category in MM. (2) Myeloid leukemia M1 cells were induced for growth arrest and
      apoptosis in response to interleukin-6. The results supported our previous
      findings and showed that PT could be evaluated by protecting the cells from
      interleukin-6 induced apoptosis. In conclusion, PT could induce interleukin-6
      dependent XG-7 and SKO-007 cells to apoptosis while inhibit interleukin-6
      stimulated apoptosis in M1 cells.

PMID- 16626852
TI  - An approach of encoding for prediction of splice sites using SVM.
AB  - In splice sites prediction, the accuracy is lower than 90% though the sequences
      adjacent to the splice sites have a high conservation. In order to improve the
      prediction accuracy, much attention has been paid to the improvement of the
      performance of the algorithms used, and few used for solving the fundamental
      issues, namely, nucleotide encoding. In this paper, a predictor is constructed to
      predict the true and false splice sites for higher eukaryotes based on support
      vector machines (SVM). Four types of encoding, which were mono-nucleotide (MN)
      encoding, MN with frequency difference between the true sites and false sites
      (FDTF) encoding, Pair-wise nucleotides (PN) encoding and PN with FDTF encoding,
      were applied to generate the input for the SVM. The results showed that PN with
      FDTF encoding as input to SVM led to the most reliable recognition of splice
      sites and the accuracy for the prediction of true donor sites and false sites
      were 96.3%, 93.7%, respectively, and the accuracy for predicting of true acceptor
      sites and false sites were 94.0%, 93.2%, respectively.

PMID- 16626853
TI  - Potyvirus terminal protein VPg, effector of host eukaryotic initiation factor
      eIF4E.
AB  - Potyvirus RNA contains at the 5' end a covalently linked virus-encoded protein
      VPg, which is required for virus infectivity. This role has been attributed to
      VPg interaction with the eukaryotic translation initiation factor eIF4E, a cap
      binding protein. We characterized the dissociation constants for the interaction
      of the potato virus Y VPg with different plant eIF4Es and its isoforms and mapped
      the eIF(iso)4E attachment region on VPg. VPg/eIF4E interaction results in the
      inhibition of cell-free protein synthesis, and we show that it stems from the
      liberation of the cap moiety from the complex with eIF4E. Since VPg does not
      attach the cap, it appears that VPg induces changes in the eIF4E structure,
      diminishing its affinity to the cap. We show here that the initiation complex
      scaffold protein eIF(iso)4G increases VPg interaction with eIF(iso)4E. These data
      together suggest similar cap and VPg interactions with eIF4E and characterize VPg
      as a novel eIF4E-binding protein, which inhibits host protein synthesis at a very
      early stage of the initiation complex formation through the inhibition of cap
      attachment to the initiation factor eIF4E.

PMID- 16626854
TI  - Renal cell carcinoma with inferior vena cava invasion: an orphan disease?

PMID- 16626855
TI  - Expanding the indications for elective partial nephrectomy: is this advisable?

PMID- 16626856
TI  - Duration of testosterone suppression after a 9.45 mg implant of the GnRH-analogue
      buserelin in patients with localised carcinoma of the prostate a 12-month follow
      up study.
AB  - OBJECTIVES: (1) To determine the duration of androgen deprivation after a single
      buserelin implant 9.45 mg in the neoadjuvant setting in combination with curative
      radiation therapy of carcinoma of the prostate, and (2) to evaluate the time to
      recovery of gonadal function, and the incidence and duration of hypogonadal
      symptoms. METHODS: We prospectively evaluated 21 men with carcinoma of the
      prostate who received one implant of 9.45 mg buserelin subcutaneously. Release of
      buserelin, changes in serum testosterone concentration, hot flushing and sexual
      function over a 12-month study period were recorded. RESULTS: Testosterone was
      suppressed below the castration limit (0.58 ng/ml=2 nmol/l) for 224 days (range,
      139-309). The mean time to first return of testosterone above the castration
      limit was 246 days (range, 168-344); 50% of pre-treatment value was reached after
      285 days (range, 218-370). The prevalence of hot flushing was 19 of 21 patients
      (90%) at 12 weeks. At the end of the study period, serum testosterone had reached
      80% (range, 33%-166%) of pre-treatment concentration, sexual interest was present
      in 52%, erection was possible in 60%, and hot flushing remained in 24%.
      CONCLUSION: A single injection of 3-month buserelin implant 9.45 mg suppresses
      serum testosterone below the castration limit for at least 6 months. Testosterone
      secretion recovers by 8-12 months. Hypogonadal symptoms decreased with the
      restoration of serum testosterone secretion. These data are clinically relevant
      regarding the dose schedule for buserelin and the patient information provided.

PMID- 16626857
TI  - Foreseeing cancer metastases.

PMID- 16626858
TI  - High radical prostatectomy surgical volume is related to lower radical
      prostatectomy total hospital charges.
AB  - OBJECTIVE: To test the hypothesis that individual surgical volume (SV) is an
      independent predictor of radical prostatectomy (RP) total charges. METHODS: We
      used the Florida State Inpatient Data File. ICD-9 codes 60.5 (RP) and 185
      (prostate cancer) identified all men treated with RP for prostate cancer between
      January 1 and December 31, 1998. Among 1,923,085 records, 3167 RPs were selected.
      SV represented the predictor. Total RP charges represented the outcome. Age,
      race, and comorbidity represented covariates. Univariate and multivariate linear
      regression models were used. RESULTS: All 3167 RPs were performed by 81 surgeons.
      SV ranged from 2 to 162 (mean, 68). Charges were 4755 dollars to 140,201 dollars
      (mean, 18,200 dollars). In the multivariate model, each SV increment
      corresponding to one RP reduced hospital charges by 25 dollars (p < or = 0.001).
      CONCLUSIONS: Redistribution of RPs from low to high SV users could result in
      significant savings. For example, 4 million dollars could be saved if 1000 RPs
      were redistributed from surgeons with an SV of 18 to surgeons with an SV of 200.

PMID- 16626859
TI  - Plasmacytoid urothelial carcinoma of the urinary bladder report of seven new
      cases.
AB  - INTRODUCTION: Plasmacytoid urothelial carcinoma (PUC) is a rare tumor of the
      urinary bladder. Its clinical and histopathological features have not been well
      characterized. In this study we report seven cases of PUC from our institution.
      MATERIALS AND METHODS: A pilot case of PUC was recently diagnosed at our
      institution. Cases of urothelial carcinoma (UC) were reviewed for a period of
      seven years to identify PUC. Representative sections from each case of PUC were
      submitted for immunohistochemical studies. Clinical charts were reviewed.
      RESULTS: There were a total of seven cases of PUC out of 260 cases of invasive
      urothelial carcinoma. The common type of urothelial carcinoma (CUC) was present
      in focal areas in five cases. Cases with extensive PUC showed coarse and
      indurated mucosal folds and thickened bladder walls, with no grossly identifiable
      tumor. Urine cytology showed a scant number of atypical single cells, frequently
      without tumor diathesis, leading to a shortfall in the positive cytological
      diagnosis. Histologically, PUC appeared as dyscohesive, plasmacytoid cells with
      eccentric nuclei, extending widely into the bladder walls and extensively into
      adjacent pelvic organs. CONCLUSION: PUC is a distinct clinical and pathological
      subtype of urothelial carcinoma. The clinical presentation is frequently late due
      to the frequent absence of hematuria and indurated mucosal surface at cystoscopy.
      The disease followed an ominous course with recurrence in all the patients, and
      with patient death.

PMID- 16626860
TI  - Nonseminomatous germ cell tumor after chemotherapy with residual mass invading
      the spine.
AB  - Bony metastasis is a rare feature of metastatic nonseminomatous germ cell tumor.
      A 25 year-old man presented with back pain radiating down both legs, and a
      subsequent work-up demonstrated a right-sided testicular mass with bilateral
      retroperitoneal lymphadenopathy and tumor involvement of the L2 vertebra. Radical
      inguinal orchiectomy confirmed nonseminomatous germ cell tumor, and the patient
      underwent chemotherapy with a residual mass and vertebral involvement by MRI.
      Combined vertebral resection with spinal reconstruction and retroperitoneal lymph
      node dissection demonstrated residual fibrosis. While bony metastasis of
      nonseminomatous germ cell tumors is rare, resection with spinal reconstruction
      can be accomplished with acceptable morbidity.

PMID- 16626861
TI  - Neuroactive steroids prevent peripheral myelin alterations induced by diabetes.
AB  - The effect of the neuroactive steroids progesterone, dihydroprogesterone and
      tetrahydroprogesterone on myelin abnormalities induced by diabetes was studied in
      the sciatic nerve of adult male rats treated with streptozotocin. Streptozotocin
      increased blood glucose levels and decreased body weight gain, parameters not
      affected by steroids. Streptozotocin increased the number of fibers with myelin
      infoldings in the axoplasm, 8 months after the treatment. Chronic treatment for 1
      month with progesterone and dihydroprogesterone resulted in a significant
      reduction in the number of fibers with myelin infoldings to control levels.
      Treatment with tetrahydroprogesterone did not significantly affect this myelin
      alteration. These results suggest that neuroactive steroids such as progesterone
      and dihydroprogesterone may represent therapeutic alternatives to counteract
      peripheral myelin alterations induced by diabetes.

PMID- 16626862
TI  - Reuptake of L-DOPA-derived extracellular dopamine in the striatum with
      dopaminergic denervation via serotonin transporters.
AB  - The aim of our present study was to determine whether exogenous L-DOPA-derived
      extracellular dopamine (DA) in the denervated striatum is taken up via serotonin
      (5-HT) transporters. Rats with dopaminergic denervation by 6-hydroxydopamine were
      injected with L-DOPA 50 mg/kg (i.p.) and extracellular DA levels in the
      denervated striatum were measured using in vivo microdialysis technique. During
      the experiments, fluoxetine, a selective serotonin reuptake inhibitor, was
      locally perfused into the striatum through the microdialysis probe. Cumulative
      amounts of L-DOPA-derived extracellular DA during 300 min were increased by
      fluoxetine dose-dependently (10 microM and 50 microM). These results suggest that
      reuptake of DA via 5-HT transporters plays an important role in the clearance of
      L-DOPA-derived DA from the extracellular space when dopaminergic neurons are
      extensively denervated.

PMID- 16626864
TI  - Molecular characterization and localization of Plasmodium falciparum choline
      kinase.
AB  - Generation of phosphocholine by choline kinase is important for
      phosphatidylcholine biosynthesis via Kennedy pathway and phosphatidylcholine
      biosynthesis is essential for intraerythrocytic growth of malaria parasite. A
      putative gene (Gene ID PF14_0020) in chromosome 14, having highest sequence
      homology with choline kinase, has been identified by BLAST searches from P.
      falciparum genome sequence database. This gene has been PCR amplified, cloned,
      over-expressed and characterized. Choline kinase activity of the recombinant
      protein (PfCK) was validated as it catalyzed the formation of phosphocholine from
      choline in presence of ATP. The K(m) values for choline and ATP are found to be
      145+/-20 microM and 2.5+/-0.3 mM, respectively. PfCK can phosphorylate choline
      efficiently but not ethanolamine. Southern blotting indicates that PfCK is a
      single copy gene and it is a cytosolic protein as evidenced by Western
      immunoblotting and confocal microscopy. A model structure of PfCK was constructed
      based on the crystal structure of choline kinase of C. elegans to search the
      structural homology. Consistent with the homology modeling predictions, CD
      analysis indicates that the alpha and beta content of PfCK are 33% and 14%,
      respectively. Since choline kinase plays a vital role for growth and
      multiplication of P. falciparum during intraerythrocytic stages, we can suggest
      that this well characterized PfCK may be exploited in the screening of new
      choline kinase inhibitors to evaluate their antimalarial activity.

PMID- 16626865
TI  - Inhibition of mevalonate 5-diphosphate decarboxylase by fluorinated substrate
      analogs.
AB  - Mevalonate 5-diphosphate decarboxylase (MDD) is a peroxisomal enzyme in the
      cholesterol biosynthetic pathway, which plays an important role in regulating
      cholesterol biosynthesis. In the present study, rat MDD was cloned and purified
      to apparent homogeneity. Two fluorinated MDD substrate analogs, P'-geranyl 2
      fluoromevalonate 5-diphosphate (4) and 2-fluoromevalonate 5-diphosphate (6), were
      synthesized, and both were found to be irreversible inhibitors of rat MDD. These
      two inhibitors were characterized, and mechanisms of the inactivation process
      were proposed. Kinetic studies indicate both analogs only bind into mevalonate
      binding-site of MDD. Compound 4 shows competitive inhibition on mevalonate kinase
      (MVK), and its IC(50) value was determined to be comparable with that of geranyl
      diphosphate. Further kinetic studies indicate compound 4 only bind into ATP
      binding-site of MVK. These studies provide an example for a single inhibitor to
      carry out sequential blocking of two enzymes in cholesterol biosynthesis, which
      may provide useful information for drug discovery for the purpose of treating
      cardiovascular disease and cancer or for pest control.

PMID- 16626866
TI  - Morphological properties of mouse retinal ganglion cells.
AB  - The mouse retina offers an increasingly valuable model for vision research given
      the possibilities for genetic manipulation. Here we assess how the structural
      properties of mouse retinal ganglion cells relate to the stratification pattern
      of the dendrites of these neurons within the inner plexiform layer. For this
      purpose, we used 14 morphological measures to classify mouse retinal ganglion
      cells parametrically into different clusters. Retinal ganglion cells were labeled
      in one of three ways: Lucifer Yellow injection, 'DiOlistics' or transgenic
      expression of yellow fluorescent protein. The resulting analysis of 182 cells
      revealed 10 clusters of monostratified cells, with dendrites confined to either
      On or Off sublaminae of the inner plexiform layer, and four clusters of
      bistratified cells, dendrites spanning the On and Off sublaminae. We also sought
      to establish how these parametrically identified retinal ganglion cell clusters
      relate to cell types identified previously on the basis of immunocytochemical
      staining and the expression of yellow fluorescent protein. Cells labeled with an
      antibody against melanopsin were found to be located within a single cluster,
      while those labeled with the SMI-32 antibody were in four different clusters.
      Yellow fluorescent protein expressing cells were distributed within 13 of the 14
      clusters identified here, which demonstrates that yellow fluorescent protein
      expression is a useful method for labeling virtually the entire population of
      mouse retinal ganglion cells. Collectively, these findings provide a valuable
      baseline for future studies dealing with the effects of genetic mutations on the
      morphological development of these neurons.

PMID- 16626867
TI  - I.c.v. administration of the nonsteroidal glucocorticoid receptor antagonist, CP
      472555, prevents exacerbated hypoglycemia during repeated insulin administration.
AB  - Hypoglycemia elicits an integrated array of CNS-mediated counterregulatory
      responses, including activation of the hypothalamic-pituitary-adrenal axis. The
      role of antecedent adrenocortical hypersecretion in impaired glucose
      counterregulation remains controversial. The present studies utilized the
      selective, nonsteroidal glucocorticoid receptor antagonist, CP-472555, as a
      pharmacological tool to investigate the hypothesis that hypoglycemic
      hypercorticosteronemia modulates CNS efferent autonomic and neuroendocrine motor
      responses to recurring insulin-induced hypoglycemia via glucocorticoid receptor
      dependent mechanisms. Groups of adult male rats were injected s.c. with either
      one or four doses of the intermediate-acting insulin, Humulin neutral protamine
      Hagedorn (NPH), on as many days, while controls were injected with diluent alone.
      Animals injected with four doses of insulin were pretreated by i.c.v.
      administration of graded doses of the glucocorticoid receptor antagonist or
      vehicle alone prior to the first three doses of insulin. Repeated daily injection
      of NPH exacerbated hypoglycemia, attenuated patterns of glucagon and epinephrine
      secretion, and diminished neuronal transcriptional activation in discrete CNS
      metabolic loci, including the lateral hypothalamic area, dorsomedial hypothalamic
      nucleus, paraventricular hypothalamic nucleus, and nucleus of the solitary tract.
      While i.c.v. delivery of 25 or 100 ng doses of CP-472555 did not alter any of
      these parameters, animals treated with 500 ng exhibited circulating glucose,
      glucagon, and epinephrine levels that were similar to those in rats injected with
      one dose of insulin, as well as a reversal of recurring insulin-induced
      hypoglycemia-associated reductions in Fos immunolabeling in the lateral
      hypothalamic area, dorsomedial hypothalamic nucleus, and paraventricular
      hypothalamic nucleus. These results provide unique pharmacological evidence that
      antecedent activation of central glucocorticoid receptor is required for
      exacerbation of hypoglycemia during recurring insulin-induced hypoglycemia, and
      that these receptors mediate modulatory effects of hypoglycemic
      hypercorticosteronemia on autonomic efferent responses to recurring insulin
      induced hypoglycemia. The data also suggest that neurons in central loci
      characterized here by antagonist-mediated overturn of recurring insulin-induced
      hypoglycemia-induced decreases in neuronal transcriptional activation may be
      direct or indirect substrates for this hormonal modulation action.

PMID- 16626868
TI  - Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1
      R) in the cochlea: evidence for specific transcript expression of PAC1-R splice
      variants in rat microdissected cochlear subfractions.
AB  - Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a neuropeptide
      originally isolated from the hypothalamus, named for its high potency in
      stimulating adenylyl cyclase in pituitary cells. PACAP acts through the specific
      receptor PAC1-R to modulate the action of neurotransmitters, and additionally, to
      regulate cell viability via autocrine/intracrine mechanisms. Evidence has now
      been obtained that PACAP and multiple splice variants of PAC1-R are expressed in
      the rat cochlea. mRNA for PACAP precursor protein is found by reverse
      transcription-polymerase chain reaction (RT-PCR) in microdissected cochlear
      lateral wall, organ of Corti, and spiral ganglion subfractions. A specific
      pattern of expression of mRNA for PAC1-R splice variants, which mediate the
      response to PACAP, has been revealed by RT-PCR and cloning for the cochlear
      subfractions. Transcript for the short form of PAC1-R is found in all three
      subfractions. Four additional splice variants -- hop1, hop2, hip, and a novel
      hop1 splice variant -- are expressed in the lateral wall. For the amino terminus
      splice region of PAC1-R, a new splice variant has been detected in the organ of
      Corti, representing a deletion of the first 7 of 21 amino acids detected in the
      PAC1-R very-short sequence. Overall, from message determinations in cochlear
      subfractions, there are five PAC1-R splice variants in the lateral wall, two in
      the organ of Corti and one in the spiral ganglion, indicating multiple possible
      responses to PACAP and/or mechanisms to modulate the response to PACAP in the
      cochlea. The variety of PAC1-R splice variants expressed may reflect the
      diversity in cell function between subfractions that is modulated by PACAP. The
      neuropeptide and its specific receptor have been immunolocalized in the lateral
      wall, the source of the largest number of cochlear PAC1-R splice variants. The
      receptor was targeted by primary antibodies which would elicit immunoreactivity
      for all splice variants of PAC1-R detected with RT-PCR, and evidence has been
      obtained with Western blot analysis suggesting that PAC1-R is glycosylated in
      vivo. Within the lateral wall, PACAP and PAC1-R were immunolocalized primarily to
      the stria vascularis, with immunoreactivity for both neuropeptide and receptor
      increasing from the basal to apical cochlear turns. Within the stria, PACAP
      immunoreactivity was localized to the basolateral extensions of marginal cells,
      while PAC1-R was clearly associated with tight junctions between the marginal
      cells close to the endolymphatic compartment. In addition, evidence was obtained
      that PAC1-R was associated with endothelial cells of the capillaries in the stria
      vascularis. The large number of splice variants expressed, coupled to the
      specificity in linkage between PAC1-R splice variants and G-protein-coupled
      second messenger pathways, could provide a mechanism to closely modulate tight
      junction integrity in the stria vascularis, impacting the endolymphatic
      potential.

PMID- 16626869
TI  - Distribution of hypothalamic, hippocampal and other limbic peptidergic neuronal
      cell bodies giving rise to retinopetal fibers: anterograde and retrograde tracing
      and neuropeptide immunohistochemical studies.
AB  - In our present work utilizing the retrograde or anterograde transport of tracers
      (biotinylated dextran amine and Fluorogold, respectively) we have provided direct
      evidence for the cells of origin of the limboretinal pathway in rats and their
      termination in the retina using light microscopic approach. Administration of
      biotinylated dextran amine into the vitreous body resulted in nerve cell body
      labeling in several structures: the supraoptic and paraventricular nuclei, the
      hippocampus (CA1, CA3), the dentate gyrus, the indusium griseum, the olfactory
      tubercle, and the medial habenula, all of them belong to the limbic system. We
      estimated that the total number of retrogradely labeled cells is 1495+/-516. We
      have seen fiber labeling in the retinorecipient suprachiasmatic nucleus and in
      the primary visual center, the lateral geniculate body, but labeled nerve cell
      bodies in these structures were never seen. Iontophoretic application of
      Fluorogold into the hippocampal formation, where the major part of the
      biotinylated dextran amine-labeled cell bodies was observed, resulted in labeled
      fibers in the optic nerve and in the retina indicating that the retrogradely
      labeled cells in the hippocampus and the dentate gyrus among others are the cells
      of origin of the centrifugal visual fibers. Sections showing biotinylated dextran
      amine labeling were stained for vasoactive intestinal polypeptide, pituitary
      adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone
      immunoreactivity using immunohistochemistry. Some biotinylated dextran amine
      labeled cells also showed vasoactive intestinal polypeptide, pituitary adenylate
      cyclase activating polypeptide or luteinizing hormone-releasing hormone
      immunoreactivity. We conclude that the limboretinal pathway exists and that the
      cells of origin are partially vasoactive intestinal polypeptide, pituitary
      adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone
      immunoreactive.

PMID- 16626870
TI  - Barosensory cells in the nucleus tractus solitarius receive convergent input from
      group III muscle afferents and central command.
AB  - Some neural mechanism must prevent the full expression of the baroreceptor reflex
      during static exercise because arterial blood pressure increases even though the
      baroreceptors are functioning. Two likely candidates are central command and
      input from the thin fiber muscle afferents evoking the exercise pressor reflex.
      Recently, activation of the mesencephalic locomotor region, an anatomical locus
      for central command, was found to inhibit the discharge of nucleus tractus
      solitarius cells that were stimulated by arterial baroreceptors in decerebrated
      cats. In contrast, the effect of thin fiber muscle afferent input on the
      discharge of nucleus tractus solitarius cells stimulated by baroreceptors is not
      known. Consequently in decerebrated unanesthetized cats, we examined the
      responses of barosensory nucleus tractus solitarius cells to stimulation of thin
      fiber muscle afferents and to stimulation of the mesencephalic locomotor region,
      a maneuver which evoked fictive locomotion. We found that electrical stimulation
      of either the mesencephalic locomotor region or the gastrocnemius nerve at
      current intensities that recruited group III afferents inhibited the discharge of
      nucleus tractus solitarius cells receiving baroreceptor input. We also found that
      the inhibitory effects of both gastrocnemius nerve stimulation and mesencephalic
      locomotor region stimulation converged onto the same barosensory nucleus tractus
      solitarius cells. We conclude that the nucleus tractus solitarius is probably the
      site whereby input from both central command and thin fiber muscle afferents
      function to reset the baroreceptor reflex during exercise.

PMID- 16626871
TI  - Sex and gonadal steroid modulation of pheromone receptor gene expression in the
      mouse vomeronasal organ.
AB  - Non-volatile chemosignals in rodents are detected by unique receptors in the
      vomeronasal organ of the accessory olfactory system. Although the vomeronasal
      organ has been implicated in the regulation of sexually dimorphic behavioral and
      neuroendocrine functions, the underlying cellular mechanisms are undetermined. In
      previous studies we showed that exposure to soiled male bedding augmented
      immediate early gene immunoreactivity in neurons of the basal zone of the
      vomeronasal organ, an effect that depended on gender and sex steroid expression.
      To determine whether this effect could be due to differences in vomeronasal organ
      receptor expression, we examined two representatives (VR1 and VR4) from different
      subfamilies of the V2R family of receptors that are expressed in the basal zone
      of the vomeronasal organ. Adult Swiss-Webster male and female mice were
      gonadectomized and implanted with capsules containing 17beta-estradiol,
      testosterone or neither steroid (control). Two weeks later vomeronasal organs
      were processed for in situ hybridization using probes from the N-terminal
      extracellular domains of VR1 and VR4. Expression of both VR1 and VR4 was
      significantly higher in males than in females. Estradiol, but not testosterone
      treated, males had significantly lower levels of VR1 expression in the caudal
      vomeronasal organ compared with untreated gonadectomized males. In contrast,
      testosterone enhanced VR4 expression in males relative to similarly treated
      females. Despite these effects, we found no evidence that vomeronasal organ
      neurons express either androgen or estrogen receptors. These data show that
      expression of vomeronasal organ receptors in mice is sexually dimorphic and
      regulated by sex steroids. Thus, gonadal hormones may affect the response of
      vomeronasal organ neurons to chemosignals by altering levels of the receptors to
      which they bind.

PMID- 16626872
TI  - Patterns of expression of brain-derived neurotrophic factor and tyrosine kinase B
      mRNAs and distribution and ultrastructural localization of their proteins in the
      visual pathway of the adult rat.
AB  - We have examined the cellular and subcellular distribution and the patterns of
      expression of brain-derived neurotrophic factor (BDNF), and of its high affinity
      receptor, tyrosine kinase B (TrkB), in retinorecipient regions of the brain,
      including the superior colliculus, the lateral geniculate nucleus and the olivary
      pretectal nucleus. In the retinorecipient layers of the superior colliculus, BDNF
      protein and mRNA were present in the cell bodies of a subpopulation of neurons,
      and BDNF protein was present in the neuropil as punctate or fiber-like
      structures. In the lateral geniculate nucleus, however, BDNF mRNA was not
      detected, and BDNF protein was restricted to punctate and fiber-like structures
      in the neuropil, especially in the most superficial part of the dorsal lateral
      geniculate nucleus, just below the optic tract. At the ultrastructural level,
      BDNF protein was localized predominantly to axon terminals containing round
      synaptic vesicles and pale mitochondria with irregular cristae, which made
      asymmetric (Gray type I) synaptic specializations (R-boutons). Enucleation of one
      eye was followed by loss of BDNF immunoreactivity and disappearance of BDNF
      positive R-boutons in the contralateral visual centers, confirming the retinal
      origin of at least most of these terminals. TrkB was present in postsynaptic
      densities apposed to immunoreactive R-boutons in the superior colliculus and
      lateral geniculate nucleus, and was also associated with axonal and dendritic
      microtubules. These findings suggest that BDNF is synthesized by a subpopulation
      of retinal ganglion cells and axonally transported to visual centers where this
      neurotrophin is assumed to play important roles in visual system maintenance
      and/or in modulating the excitatory retinal input to neurons in these centers.

PMID- 16626873
TI  - Chronic treatment with first or second generation antipsychotics in rodents:
      effects on high affinity nicotinic and muscarinic acetylcholine receptors in the
      brain.
AB  - Several postmortem and neuroimaging studies suggest that central nicotinic and
      muscarinic acetylcholine receptors are important in both the pathophysiology and
      pharmacotherapy of schizophrenia. However, while antipsychotic drugs are
      routinely used in the therapeutics of schizophrenia, little is known about their
      effects on the densities of these receptors when they are administered for
      extended periods of time (a common practice in the clinical setting). In the
      present study in rats, the residual effects of prior chronic exposure to
      representative first generation antipsychotics and second generation
      antipsychotics on the densities of high affinity nicotinic acetylcholine
      receptors and muscarinic acetylcholine receptor in the brain were investigated.
      Test subjects were treated with the first generation antipsychotics, haloperidol
      (2.0 mg/kg/day) or chlorpromazine (10.0 mg/kg/day) or the second generation
      antipsychotics, risperidone (2.5 mg/kg/day) or olanzapine (10.0 mg/kg/day) in
      drinking water for periods of 90 or 180 days, given a drug-free washout period
      (i.e. returned to normal drinking water) for two weeks and then killed.
      Quantitative receptor autoradiography was subsequently performed using 16 mum
      sagittal slices of whole brain incubated with [3H]-epibatidine, [3H]-pirenzepine
      or [3H]-AFDX-384 to measure high affinity nicotinic acetylcholine receptors, M1
      and M2 muscarinic acetylcholine receptors, respectively. The most notable
      experimental result was a moderate, but significant (P<0.01) increase in [3H]
      AFDX-384 binding sites in a number of brain regions (including cortex,
      hippocampus, subiculum, substantia innominata, and thalamus) associated with
      prior exposure to olanzapine for 90, but not 180 days. Olanzapine was also
      associated with a significantly higher density of [3H]-pirenzepine binding sites
      in cortex lamina I after 90 days of prior drug exposure. These data indicate that
      chronic treatment with a commonly used second generation antipsychotic,
      olanzapine is associated with modest increases in M2 muscarinic acetylcholine
      receptors in memory-related brain regions that may eventually abate with longer
      periods of chronic drug exposure.

PMID- 16626874
TI  - Modulation of laser-evoked potentials by experimental cutaneous tonic pain.
AB  - The present study aimed to investigate whether tonic cutaneous pain exerts any
      effect on the cortical processing of nociceptive input and if this effect may
      involve only body parts in pain. Tonic cutaneous pain was obtained in nine
      healthy human subjects by infusion of a hypertonic saline (5%) in the s.c. tissue
      over the hypothenar muscles (10 ml/h for 20 min). Nociceptive cutaneous CO2 laser
      evoked potentials were recorded after stimulation of the right hand dorsum, which
      was adjacent to the painful area, and the right perioral region, corresponding to
      the adjacent cortical sensory area. Laser-evoked potentials were obtained before
      saline injection, at the peak pain and 20 min after pain disappeared. During
      saline infusion, the laser-evoked pain to right hand stimulation was reduced and
      the vertex laser-evoked potentials (N2a-P2, mean latency 181 ms and 319 ms for
      the N2a and the P2 potentials, respectively), which are generated in the anterior
      cingulate cortex, were significantly decreased in amplitude compared with the
      baseline. Moreover, the topography of these potentials was modified by cutaneous
      pain, shifting from the central toward the parietal region. Dipolar modeling
      showed that the dipolar source in the anterior cingulate cortex moved backward
      during saline infusion. This result suggests that cutaneous pain may modify the
      relative activities of the anterior and posterior anterior cingulate cortex
      parts, which are thought to be devoted to encode different aspects of pain
      sensation. No laser-evoked potential change was observed after stimulation of the
      right perioral region, suggesting that functional changes in the nociceptive
      system are selective for the painful regions and not for areas with cortical
      proximity.

PMID- 16626875
TI  - Do anorectic men share personality traits with opiate dependent men? A case
      control study.
AB  - BACKGROUND: Eating disorders (ED) and substance use disorders (SUD) display
      clinical and psychodynamic analogies. The co-diagnosis of a substance use
      disorder in male ED patients is frequent. Nevertheless, knowledge about the
      mutual predisposing factors or personality analogies is currently scarce and
      hypotheses are controversial. METHODS: The Temperament and Character Inventory
      (TCI) was used to assess 21 anorectic men, 79 heroin-dependent men, and 75
      control men matched for age and education. RESULTS: Anorectic and opiate-addicted
      patients displayed higher Harm Avoidance and lower Self-directedness and
      Cooperativeness. Anorectic men displayed lower Reward Dependence and higher
      Persistence. Opiate addicts had higher Novelty Seeking and Self-transcendence.
      DISCUSSION: Anorectic and heroine-dependent subjects share personality traits
      related to anxiety, fearfulness and antisocial features. Nevertheless, the
      personality profile does not completely overlap and this could influence the
      choice of the "substance" of abuse and the related clinical differences between
      anorexia and heroin dependence.

PMID- 16626876
TI  - When children of problem drinkers grow old: does the increased risk of mental
      disorders persist?
AB  - It is well established that children of problem drinkers have an increased risk
      of developing mental health problems, not only during childhood but also when
      they grow up into adolescents and adults. However, it has not been examined
      whether this risk is also present during the old age of these children. In this
      study, we examine the question whether this increased risk is present in
      inhabitants of eleven residential homes (mean age 85 years). A total of 355
      residents indicated whether one of their parents ever had problems with alcohol.
      We also used the MINI diagnostic interview to assess the presence of mental
      disorders. We found that parental problem drinking was significantly associated
      with having a major depression (current and lifetime), and with the number of
      drinks in the past week. No significant relationship was found with alcohol
      related disorders and anxiety disorders. It was already known that parental
      problem drinking results in mental health problems in children. We found clear
      indications that these problems do not disappear when these children grow old.

PMID- 16626877
TI  - Symptoms of traumatic stress and substance use in a non-clinical sample of young
      adults.
AB  - The link between symptoms of traumatic stress and substance abuse is well
      established in the literature, but the specific features of trauma that
      contribute to substance abuse remain elusive and have not been studied in non
      clinical samples. The current study assessed the relationship between traumatic
      symptoms and alcohol use in a sample of Midwestern college students. Using
      multiple regression analysis, traumatic stress symptoms, overall, accounted for
      55% of the variance in use of alcohol. Most importantly, dissociative behavior,
      intrusive thoughts, as well as low levels of tension reduction behaviors uniquely
      contributed to the self-reported use of alcohol. We discuss the importance of
      educating college-aged students about this relationship as a preventative measure
      to alcohol and other drug use/abuse.

PMID- 16626878
TI  - Comparing electronic-keypad responses to paper-and-pencil questionnaires in group
      assessments of alcohol consumption and related attitudes.
AB  - Electronic versions of questionnaires have the potential to improve research and
      interventions in the addictions. Administering questionnaires electronically to
      groups, however, has proven difficult without a multitude of computers, but
      gathering data electronically from a group could make for easy assessment and
      quick feedback. Using a sample of 107 college students, we examined the validity
      of wireless keypad survey responses by comparing them to traditional paper-and
      pencil questionnaires. The two formats led to almost identical responses that did
      not differ significantly from each other (all effect sizes less than g=.15) and
      high correlations between formats. The wireless, handheld keypad procedure
      appears to generate data that are as valid as questionnaire responses and permit
      rapid feedback to groups, as well as easy, human error-free data entry for
      analysis.

PMID- 16626879
TI  - The problem of binge drinking among Italian university students: a preliminary
      investigation.
AB  - Although binge drinking and excessive alcohol consumption are relevant public
      health problems in Italy, no research has been carried out on those topics for
      years. In the first months of the year 2005, 1000 undergraduates in a number of
      Italian universities were administered a survey regarding their attitudes in
      alcohol consumption. Participants were to complete a questionnaire including
      demographic and alcohol variables, the Sensation-Seeking Scale (SSSV) and the
      Positive Drinking Expectancy Scale (PDMS). According to previous research,
      students were categorized in non-drinkers, social, binge, and heavy drinkers.
      Results showed that the estimated percentage of binge drinking among university
      students is 32.9%. The survey revealed-by means of univariate and multivariate
      analysis-that social, binge, and heavy drinkers differ in terms of some drinking
      variables, in their expectancies about alcohol and in sensation-seeking
      dimensions. Implications for the prevention of binge drinking in young adults are
      currently under discussion even if further investigation into the Italian context
      is urgently needed.

PMID- 16626880
TI  - The Adolescent Cannabis Problems Questionnaire (CPQ-A): psychometric properties.
AB  - Despite the widespread use of cannabis among young people, little research
      attention has been given to the development of psychometrically sound measures
      specific to cannabis related problems in this group. The aim of this study was to
      explore the reliability, validity and factor structure of a multi-dimensional
      measure of cannabis-related problems among adolescents. The Adolescent Cannabis
      Problems Questionnaire (CPQ-A) was developed as an assessment tool and treatment
      outcome measure. A stratified sample of 100 young people (aged 14-18 years) who
      had used cannabis in the past 90 days were administered the CPQ-A on two
      occasions 1 week apart. Exploratory factor analysis revealed three factors
      accounting for 63% of total variance with alpha coefficients of 0.88, 0.72 and
      0.73. The CPQ-A was reliable with test-retest correlation for the total CPQ-A
      being 0.91. CPQ-A score correlated significantly with frequency of cannabis use
      and number of DSM-IV dependence criteria reported. The findings show promise for
      the CPQ-A as a reliable, valid and potentially clinically useful measure of
      cannabis related problems among young people.

PMID- 16626881
TI  - Defensively biased responding to risk information among alcohol-using college
      students.
AB  - Previous research has found that individuals who engage in risky health behaviors
      respond to health risk messages in a self-serving manner, limiting the impact of
      health messages among targeted individuals. The present study sought to
      investigate whether alcohol-using college students would respond to risk messages
      about alcohol use with a similar defensive bias. Both alcohol-using (N=244) and
      non-using (N=91) college students read a summary of alcohol risk information
      intended for college students. Participants then reported their attitudes about
      the seriousness of the problem of college drinking, personal risk, and the
      scientific credibility of the risk information. Results indicated that high-risk
      participants responded in a self-serving manner, with significantly lower ratings
      of problem importance among alcohol-using students and non-significant
      differences among assessments of personal risk between groups. Further, alcohol
      using students were more critical of the scientific merit of the risk information
      and more skeptical about the empirical claims. Defensively biased responding was
      more pronounced among more frequent and heavy drinking students than among
      lighter drinking students. The implications of these findings as well as possible
      ways to reduce defensive bias are discussed.

PMID- 16626882
TI  - Beliefs about drinking problems: results from a general population telephone
      survey.
AB  - As part of a general population telephone survey (N=3006), respondents were asked
      their beliefs about alcohol problems. The majority of respondents were skeptical
      about the possibility of untreated and of moderate drinking recoveries. The
      predominant conceptions of the nature of alcohol problems were those of a disease
      or of drug addiction. Beliefs about the need for treatment and abstinence were
      positively associated with being female, older, and married. Current heavy
      drinkers were less likely to believe that treatment was needed. Former heavy
      drinkers were more likely to believe that abstinence was required, as compared to
      all other respondents.

PMID- 16626883
TI  - Future time perspective as predictor of cannabis use: exploring the role of
      substance perception among French adolescents.
AB  - This study explored the relation of Future time perspective (FTP) to cannabis use
      and tested the potential mediating role of cannabis perception, with a sample of
      276 French adolescents. FTP was assessed using ZTPI subscale, cannabis perception
      was evaluated from a list of nine items related to drug-oriented perception
      (DOP), and participants were asked to report both their cannabis use and the
      level of use. Results showed that FTP acts as a significant predictor of cannabis
      use, and is significantly linked to DOP. A significant relationship between DOP
      and cannabis use also appeared. Regression analyses showed that DOP acts as a
      mediator in the link between FTP and cannabis use. These findings confirm the
      protective role of FTP in cannabis use and suggest the indirect nature of this
      role.

PMID- 16626884
TI  - Phase I trial of erlotinib with radiation therapy in patients with glioblastoma
      multiforme: results of North Central Cancer Treatment Group protocol N0177.
AB  - PURPOSE: To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib
      plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a
      multicenter phase I trial. METHODS AND MATERIALS: Patients were stratified on the
      basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or
      biopsy, patients were treated with erlotinib for 1 week before concurrent
      erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until
      progression. The erlotinib dose was escalated in cohorts of 3 starting at 100
      mg/day. RESULTS: Twenty patients were enrolled and 19 were evaluable for the MTD
      and efficacy endpoints. Of these patients, 14 were males and 5 were females, with
      a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal
      resections, and 7 had gross total resections. The highest dose level was 150
      mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients
      on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg
      (n=6) and at 150 mg (n=4), only 1 dose-limiting toxicity (DLT) occurred
      (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n=3), 150 mg
      (n=3), and 200 mg (n=3). With a median follow-up of 52 weeks, progression was
      documented in 16 patients and 13 deaths occurred. Median time to progression was
      26 weeks, and median survival was 55 weeks. CONCLUSION: Toxicity is acceptable at
      the current doses of erlotinib plus RT. The study was modified to include
      concurrent and adjuvant temozolomide, and accrual is in progress.

PMID- 16626885
TI  - Impact of radiotherapy in the risk of esophageal cancer as subsequent primary
      cancer after breast cancer.
AB  - PURPOSE: To assess the risk of esophageal cancer as second cancer among breast
      cancer patients treated with radiotherapy. METHODS AND MATERIALS: The records of
      the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of
      esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients
      were treated with surgery (n = 33,672), radiotherapy (n = 35,057), chemotherapy
      and radiotherapy (n = 4673), or chemotherapy (n = 2,447). The risk of a new
      primary cancer was expressed as standardized incidence ratio (SIR), defined as
      the ratio of observed to expected cases. RESULTS: By the end of 2000, the number
      of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized
      incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among
      patients followed for 15 years and treated with radiotherapy, the SIR for
      esophageal cancer was 2.3 (95% CI = 1.4 to 5.4). No increase in risk was seen for
      patients treated without radiotherapy. The risk of esophageal cancer was
      increased among patients diagnosed during 1953 to 1974, although age at the
      treatment did not have marked effect on the risk estimate. CONCLUSION: Increased
      risk of second cancer in the esophagus was observed for breast-cancer patients in
      Finland, especially among patients with over 15 years of follow-up and treated in
      the earliest period, which may relate to the type of radiotherapy.

PMID- 16626886
TI  - The role of surgical margins in treatment of Ewing's sarcoma family tumors:
      experience of a single institution with 512 patients treated with adjuvant and
      neoadjuvant chemotherapy.
AB  - PURPOSE: To evaluate the importance of surgical margins for local and systemic
      control of Ewing's sarcoma family tumors (ESFT). METHODS AND MATERIALS: Between
      1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and
      neoadjuvant studies performed at a single institution. Of these patients, 335
      were treated with surgery alone (196) or surgery followed by radiotherapy at
      doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients
      who were locally treated by radiotherapy at 60 Gy. RESULTS: Local control (88.8%
      vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p <
      0.0007) were significantly better in patients treated with surgery and, among
      them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and
      69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in
      extremity tumors. CONCLUSIONS: Surgery is better than radiotherapy in cases of
      extremity ESFT with achievable adequate surgical margins, and in cases of
      inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective.
      Therefore, when inadequate margins are expected, patients are better treated with
      full-dose radiotherapy from the start.

PMID- 16626887
TI  - Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82
      cases.
AB  - BACKGROUND: The Intergroup 0116 study showed a survival benefit with adjuvant
      chemoradiotherapy (CRT) for resected gastric cancer. We report our experience
      using conformal radiotherapy (RT). METHODS AND MATERIALS: Eighty-two patients
      with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB
      to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal
      technique. Chemotherapy was in accordance with the Intergroup 0116 study, or
      infusional 5-fluorouracil and cisplatin in a phase I/II trial. RESULTS: Mean age
      was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute
      toxicity (National Cancer Institute Common Terminology Criteria of Adverse
      Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract
      34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy
      Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients)
      and small bowel obstruction (1 patient). Full course CRT was completed by 67% of
      patients. Of 26 patients who relapsed, 20 died. Site of first relapse was
      available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11
      distant alone. Overall and relapse-free survival were 69% and 54% at 3 years.
      CONCLUSION: Adjuvant CRT for gastric cancer, even with conformal RT, is
      associated with significant toxicity. Survival was comparable to that reported in
      the Intergroup 0116 study.

PMID- 16626888
TI  - Variability of gross tumor volume delineation in head-and-neck cancer using CT
      and PET/CT fusion.
AB  - PURPOSE: To assess the need for gross tumor volume (GTV) delineation protocols in
      head-and-neck cancer (HNC) treatment planning by use of positron emission
      tomography (PET)/computed tomography (CT) fusion imaging. Assessment will consist
      of interobserver and intermodality variation analysis. METHODS AND MATERIALS:
      Sixteen HNC patients were accrued for the study. Four physicians (2
      neuroradiologists and 2 radiation oncologists) contoured GTV on 16 patients.
      Physicians were asked to contour GTV on the basis of the CT alone, and then on
      PET/CT fusion. Statistical analysis included analysis of variance for
      interobserver variability and Student's paired sample t test for intermodality
      and interdisciplinary variability. A Boolean pairwise analysis was included to
      measure degree of overlap. RESULTS: Near-significant variation occurred across
      physicians' CT volumes (p = 0.09) and significant variation occurred across
      physicians' PET/CT volumes (p = 0.0002). The Boolean comparison correlates with
      statistical findings. One radiation oncologist's PET/CT fusion volumes were
      significantly larger than his CT volumes (p < 0.01). Conversely, the other
      radiation oncologist's CT volumes tended to be larger than his fusion volumes (p
      = 0.06). No significant interdisciplinary variation was seen. Significant
      disagreement occurred between radiation oncologists. CONCLUSION: Significant
      differences in GTV delineation were found between multiple observers contouring
      on PET/CT fusion. The need for delineation protocol has been confirmed.

PMID- 16626889
TI  - FDG-PET/CT in the evaluation of anal carcinoma.
AB  - PURPOSE: Surgical staging and treatment of anal carcinoma has been replaced by
      noninvasive staging studies and combined modality therapy. In this study, we
      compare computed tomography (CT) and physical examination to [(18)F]-fluoro-2
      deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in
      the staging of carcinoma of the anal canal, with special emphasis on
      determination of spread to inguinal lymph nodes. METHODS AND MATERIALS: Between
      July 2003 and July 2005, 41 consecutive patients with biopsy-proved anal
      carcinoma underwent a complete staging evaluation including physical examination,
      CT, and 2-FDG-PET/CT. Patients ranged in age from 30 to 89 years. Nine men were
      HIV-positive. Treatment was with standard Nigro regimen. RESULTS: [(18)F]-fluoro
      2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT)
      detected 91% of nonexcised primary tumors, whereas CT visualized 59%. FDG-PET/CT
      detected abnormal uptake in pelvic nodes of 5 patients with normal pelvic CT
      scans. FDG-PET/CT detected abnormal nodes in 20% of groins that were normal by
      CT, and in 23% without abnormality on physical examination. Furthermore, 17% of
      groins negative by both CT and physical examination showed abnormal uptake on FDG
      PET/CT. HIV-positive patients had an increased frequency of PET-positive lymph
      nodes. CONCLUSION: [(18)F]-fluoro-2-deoxy-D-glucose-positron emission
      tomography/computed tomography detects the primary tumor more often than CT. FDG
      PET/CT detects substantially more abnormal inguinal lymph nodes than are
      identified by standard clinical staging with CT and physical examination.

PMID- 16626890
TI  - Radiation-induced moyamoya syndrome.
AB  - PURPOSE: The moyamoya syndrome is an uncommon late complication after
      radiotherapy (RT). METHODS AND MATERIALS: A PubMed search of English-language
      articles, with radiation, radiotherapy, and moyamoya syndrome used as search key
      words, yielded 33 articles from 1967 to 2002. RESULTS: The series included 54
      patients with a median age at initial RT of 3.8 years (range, 0.4 to 47). Age at
      RT was less than 5 years in 56.3%, 5 to 10 years in 22.9%, 11 to 20 years in
      8.3%, 21 to 30 years in 6.3%, 31 to 40 years in 2.1%, and 41 to 50 years in 4.2%.
      Fourteen of 54 patients (25.9%) were diagnosed with neurofibromatosis type 1 (NF
      1). The most common tumor treated with RT was low-grade glioma in 37 tumors
      (68.5%) of which 29 were optic-pathway glioma. The average RT dose was 46.5 Gy
      (range, 22-120 Gy). For NF-1-positive patients, the average RT dose was 46.5 Gy,
      and for NF-1-negative patients, it was 58.1 Gy. The median latent period for
      development of moyamoya syndrome was 40 months after RT (range, 4-240). Radiation
      induced moyamoya syndrome occurred in 27.7% of patients by 2 years, 53.2% of
      patients by 4 years, 74.5% of patients by 6 years, and 95.7% of patients by 12
      years after RT. CONCLUSIONS: Patients who received RT to the parasellar region at
      a young age (<5 years) are the most susceptible to moyamoya syndrome. The
      incidence for moyamoya syndrome continues to increase with time, with half of
      cases occurring within 4 years of RT and 95% of cases occurring within 12 years.
      Patients with NF-1 have a lower radiation-dose threshold for development of
      moyamoya syndrome.

PMID- 16626891
TI  - Permanent prostate brachytherapy: Dosimetric results and analysis of a learning
      curve with a dynamic dose-feedback technique.
AB  - PURPOSE: A permanent prostate brachytherapy (PPB) program utilizing
      intraoperative inverse-planned dynamic dose-feedback was initiated without prior
      firsthand experience of alternative techniques. The purpose of this study is to
      assess the dosimetric learning curve associated with this approach. METHODS AND
      MATERIALS: A total of 77 patients underwent PPB implants as monotherapy for
      localized prostate cancer to a prescription dose of 145 Gy with loose 125I seeds
      between December 2003 and June 2004. Intraoperative and postoperative dosimetric
      values, total implanted radioactivity, and operating room (OR) times were
      compared by sequential case number for all cases. RESULTS: The median
      intraoperative dosimetric values were: D90 (the minimum dose to 90% of the
      prostate) = 170 Gy (range, 135-203 Gy), V100 (the volume of the prostate that
      receives 100% of the prescription dose) = 96% (range, 86-100), V150 = 66% (range,
      34-86). Median postoperative dosimetric values were as follows: D90 = 168 Gy
      (range, 132-197 Gy), V100 = 95% (range, 86-99), V150 = 74% (range, 51-84). Median
      implanted activity was 0.79 mCi per cubic centimeter of prostate (range, 0.541
      1.13). There was no significant correlation by case number on any postoperative
      dosimetric parameter studied. Door-to-door OR time was reduced from median 138 to
      97.5 min per case at the end of the series with a correlation coefficient of 
      0.76 for the initial 28 cases. CONCLUSION: Satisfactory dosimetric parameters can
      be achieved from the outset without a learning curve effect in an appropriately
      trained environment. The learning curve for dynamic dose-feedback PPB in a clinic
      naive to other techniques is apparent in terms of OR time.

PMID- 16626892
TI  - Radiation dose to the internal pudendal arteries from permanent-seed prostate
      brachytherapy as determined by time-of-flight MR angiography.
AB  - PURPOSE: To determine the feasibility of time-of-flight magnetic resonance (MR)
      angiography to visualize the internal pudendal arteries (IPAs) in potent men
      undergoing permanent-seed prostate brachytherapy and to calculate the radiation
      dose received by these arteries. METHODS AND MATERIALS: Prostate brachytherapy is
      performed at the University Health Network/Princess Margaret Hospital by use of
      transrectal ultrasound (TRUS) preplanning and preloaded needles. All patients
      received (125)I, with a mean seed activity of 0.32 mCi/seed (0.41 U). Postplan
      evaluation is performed at 1 month by magnetic resonance-computed tomography
      fusion. Twenty consecutive potent men had time-of-flight MR angiography as part
      of their postplan evaluation. RESULTS: The mean V100 was 96.5%, and the mean D90
      was171.5 Gy. The IPAs were easily visualized for 18 of the 20 men. The mean peak
      dose received by the IPA was 17 Gy. The highest peak dose received by any patient
      was 38.2 Gy, with only 1 other patient receiving a peak dose greater than 30 Gy.
      Eleven of 18 had a measurable portion of at least 1 IPA that received 10% of the
      prescribed dose (V10 = 14.5 Gy). Only 2 patients had nonzero values for V25. The
      distal third of the IPA received the highest dose for 16 of the 18 patients.
      CONCLUSIONS: The IPAs can be well visualized in the majority of potent men by use
      of time-of-flight MR angiography 1 month after brachytherapy. The IPAs receive a
      low but calculable dose from permanent-seed (125)I brachytherapy. Further
      research is needed to determine if this outcome has any correlation with
      subsequent potency.

PMID- 16626893
TI  - Expression of PRL proteins at invasive margin of rectal cancers in relation to
      preoperative radiotherapy.
AB  - PURPOSE: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of
      colorectal cancer; however, its therapeutic implication in cancer patients has
      not been studied. We investigated the relationships of PRL expression to
      radiotherapy (RT) in rectal cancer patients. METHODS AND MATERIALS: Phosphatase
      of regenerating liver expression was immunohistochemically examined in distant (n
      = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy
      specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer
      patients participating in a clinical trial of preoperative RT. RESULTS:
      Phosphatase of regenerating liver expression was increased from the distant to
      adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at
      the invasive margin in 28% of the primary tumors and 26% of the metastases. In
      the RT group, strong PRL expression at the invasive margin was related to distant
      recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group.
      The survival significance remained even after adjusting for Dukes' stage and
      differentiation (p = 0.02). Additional multivariate analyses showed that the
      correlation with prognostic significance of PRL differed between the RT and non
      RT groups (p = 0.01). CONCLUSION: Phosphatase of regenerating liver expression
      (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and
      unfavorable survival in rectal cancer patients with preoperative RT.

PMID- 16626894
TI  - Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma
      of the uterine cervix.
AB  - PURPOSE: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT)
      for locally advanced cervical cancer by two phase I/II clinical trials. METHODS
      AND MATERIALS: Between June 1995 and January 2000, 44 patients were treated with
      CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA
      disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment
      consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local
      boost. In the first study, the total dose ranged from 52.8 to 72.0 gray
      equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole
      pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given
      to the cervical tumor (total dose, 68.8 or 72.8 GyE). RESULTS: No patient
      developed severe acute toxicity. In contrast, 8 patients developed major late
      gastrointestinal complications. The doses resulting in major complications were >
      or =60 GyE. All patients with major complications were surgically salvaged. The 5
      year local control rate for patients in the first and second studies was 45% and
      79%, respectively. When treated with > or =62.4 GyE, the local control was
      favorable even for the patients with stage IVA disease (69%) or for those with
      tumors > or =6.0 cm (64%). CONCLUSIONS: In CIRT for advanced cervical cancer, the
      dose to the intestines should be limited to <60 GyE to avoid major complications.
      Although the number of patients in this study was small, the results support
      continued investigation to confirm therapeutic efficacy.

PMID- 16626895
TI  - Identification and expression of novel isoforms of human stromal cell-derived
      factor 1.
AB  - Stromal Cell-derived factor 1 (SDF-1) is a CXC chemokine that binds to the CXCR4
      receptor. Recent publication indicates that the SDF-1/CXCR4 signaling pathway
      plays a pivotal role during development and in many patho-physiological
      conditions including hematopoiesis, blood vessel formation, cancer metastasis,
      angiogenesis and HIV infection. Two human SDF-1 isoforms, SDF-1alpha and SDF
      1beta, have been reported to date. Here we report the identification of four
      additional human SDF-1 isoforms derived from alternative splicing events, SDF
      1gamma, SDF-1delta, SDF-1epsilon and SDF-1phi. These SDF-1 splice variants all
      share the same first three exons but contain different fourth exons. The human
      SDF-1 gene spans over 88 kilobase-pairs on chromosome 10. Using the semi
      quantitative RT-PCR method, we determined the tissue distribution of these SDF-1
      isoforms. SDF-1alpha and SDF-1beta share similar expression patterns and the
      highest expression were detected in liver, pancreas and spleen. SDF-1gamma seems
      to be the human orthologue of recently isolated rat SDF-1gamma, and its
      expression was only detected in the heart. SDF-1delta expression can be detected
      in several adult tissues but the highest expression was detected in fetal liver.
      When transfected into HEK293 cells, all the SDF-1 isoforms can be detected as
      secreted proteins in the cell culture media. The conditioned media from
      transfected cells can stimulate cell migration in a CXCR4-dependent manner. These
      data suggest that the novel SDF-1 splice variants encode functional proteins.

PMID- 16626896
TI  - Assessing the microsporidia-fungi relationship: Combined phylogenetic analysis of
      eight genes.
AB  - Microsporidia are unicellular eukaryotes that are obligate parasites of a variety
      of animals. For many years, microsporidia were thought to be an early offshoot of
      the eukaryotic evolutionary tree, and early phylogenetic work supported this
      hypothesis. More recent analyses have consistently placed microsporidia far from
      the base of the eukaryotic tree and indicate a possible fungal relationship, but
      the nature of the microsporidian-fungal relationship has yet to be determined.
      The concatenated dataset employed in this analysis consists of eight genes and
      contains sequence data from representatives of four fungal phyla. A consistent
      branching pattern was recovered among four different phylogenetic methods. These
      trees place microsporidia as a sister to a combined ascomycete+basidiomycete
      clade. AU tests determined that this branching pattern is the most likely, but
      failed to reject two alternatives.

PMID- 16626897
TI  - Ongoing loss of the tirant transposable element in natural populations of
      Drosophila simulans.
AB  - Tirant is a long terminal repeat (LTR) retrotransposon with an average of 11
      insertion sites on the chromosome arms of Drosophila melanogaster flies collected
      from natural populations worldwide. In the sibling species Drosophila simulans,
      tirant is found only in African populations, which harbor a few insertion sites
      (1 to 5) on the chromosome arms, although some tirant sequences are present in
      the heterochromatin of most populations. This distribution in D. simulans
      reflects either the recent genomic invasion of African populations by a new
      variant of tirant, or a loss of tirant from the entire species apart from some
      sequence relics still present in Africa. In an attempt to clarify the situation,
      we focused on the LTR-UTR region of tirant copies from various populations of
      both D. melanogaster and D. simulans. We found two distinct types of regulatory
      region: one type was present in both D. melanogaster and D. simulans, and the
      other was present only in D. simulans. Copies of this latter type of tirant were
      transcriptionally inactive in gonads. Here we propose that the present day
      distribution of tirant in D. simulans populations reflects an ancient invasion of
      D. simulans by tirant copies followed by the loss of active copies from most
      populations, apart from the African ones, suggesting that this loss is still
      ongoing in this species.

PMID- 16626898
TI  - Bacterial lipopolysaccharide induces porcine circovirus type 2 replication in
      swine alveolar macrophages.
AB  - Monocyte/macrophage lineage cells are major target cells of porcine circovirus
      type 2 (PCV2). From tissues of field pigs suffering from postweaning
      multisystemic wasting syndrome (PMWS), both intracytoplasmic and intranuclear
      PCV2 signals, including antigens and nucleic acid, were easily detected in the
      monocyte/macrophage lineage cells. However, there was a high incidence of
      intracytoplasmic PCV2-positive signals, but lack of intranuclear signals and PCV2
      replication in these cells in vitro. Concurrent infection with bacteria and
      activation of immune system are suggested to promote viral replication. In this
      study, lipopolysaccharide (LPS) and phorbol-12-myristate-13-acetate (PMA) were
      used to stimulate PCV2-inoculated alveolar macrophages (AMs). A decrease in
      intracytoplasmic but increase in intranuclear PCV2-positive signals, including
      antigens and nucleic acid, were detected in LPS-treated PCV2-inoculated AMs, but
      not in PMA-treated cells. Additionally, the replication product corresponding to
      PCV2 spliced major capsid protein (Cap) mRNA and a significant elevation in PCV2
      titer were demonstrated in the LPS-treated PCV2-inoculated AMs. The results imply
      that Gram-negative bacterial co-infection in PCV2-infected pigs may be an
      important factor in promoting PCV2 replication and contributing, at least
      partially, to the full development of PMWS.

PMID- 16626899
TI  - Do former preterm infants remember and respond to neonatal intensive care unit
      noise?
AB  - BACKGROUND: Previous studies have shown that 4-month-old infants have a decrease
      in heart rate, a component of the orienting reflex, in response to interesting
      auditory stimuli and an increase in heart rate to aversive auditory stimuli.
      OBJECTIVE: To compare the heart rate responses of former preterm and term infants
      at 4-5 months corrected age to a recording of NICU noises. METHODS: 13 former
      preterm infants and 17 full-term infants were presented NICU noise and another
      noise of similar level and frequency content in random order. Heart rate 10s
      prior to the stimulus and for 20s during the stimulus was analyzed. Group
      differences in second by second heart rate changes in response to the two noise
      stimuli were compared by analysis of covariance. RESULTS: Both the preterm and
      term newborns responded similarly to the NICU noise and the control noise. The
      preterm infants did not alter their heart rate in response to either stimulus. In
      contrast, the term infants displayed an orienting response to the second stimulus
      presented regardless of whether it was the NICU or control noise. CONCLUSIONS:
      Former preterm infants at 4-5 months corrected age have reduced responsiveness to
      auditory stimulation in comparison to 4- to 5-month-old term infants.
      Furthermore, they did not respond to the NICU noise as an aversive stimulus.

PMID- 16626900
TI  - Prenatal bowel dilatation and the subsequent postnatal management.
AB  - The presence of dilated bowel loops antenatally suggests fetal bowel obstruction.
      Neonatal intestinal obstruction can have different variations in presentation
      depending on the level and extent of obstruction. Some of these conditions can be
      diagnosed antenatally. Antenatal detection of surgically correctable anomalies
      would ideally reduce perinatal morbidity and mortality by allowing a planned
      delivery with early resuscitation and prompt surgical intervention. Duodenal
      atresia is the most common intestinal atresia diagnosed in a fetus. Presently
      there are no significant abnormalities of the fetal gastrointestinal tract that
      benefit from fetal intervention. However a thorough understanding of the disease
      processes is necessary for diagnosis and treatment of intestinal obstruction.
      With advances in neonatal intensive care and management there has been a
      significant decrease in mortality rates of neonates with intestinal obstruction.

PMID- 16626901
TI  - Increased expression of extracellular proteins as a hallmark of human endothelial
      cell in vitro senescence.
AB  - A convenient way to study processes of aging in distinct human tissues consists
      of a molecular analysis of cells from the tissue in question, that were explanted
      and grown in vitro until they reach senescence. Using human umbilical vein
      endothelial cells (HUVEC), we have established an in vitro senescence model for
      human endothelial cells. A major hallmark of HUVEC in vitro senescence is the
      increased frequency of apoptotic cell death, which occurs as a determining
      feature of HUVEC senescence. Senescent endothelial cells are also found in vivo
      in atherosclerotic lesions, suggesting that the presence of such cells may
      contribute to the development of vascular pathology. To elucidate mechanisms
      underlying endothelial cell senescence and age-associated apoptosis, gene
      expression analyses were carried out. In these experiments, we observed the up
      regulation of genes coding for extracellular proteins in senescent HUVEC. In
      particular, a significant upregulation of interleukin-8, VEGI, and the IGF
      binding proteins 3 and 5 was observed. Upregulation of these genes was confirmed
      by both RT-PCR and Western blot. In the case of interleukin-8, a roughly 50-fold
      upregulation of the protein was also found in cellular supernatants. The
      extracellular proteins encoded by these genes are well known for their ability to
      modulate the apoptotic response of human cells, and in the case of interleukin-8,
      clear links to the establishment of atherosclerotic lesions have been defined.
      The results described here support a new model, where changes in the secretome of
      human endothelial cells contribute to vascular aging and vascular pathology.

PMID- 16626902
TI  - Rapid identification of Enterobacteriaceae by sequencing DNA gyrase subunit B
      encoding gene.
AB  - Real-time polymerase chain reaction and sequencing were used to characterize a
      506-bp-long DNA fragment internal to the gyrB gene (gyrBint). The sequences
      obtained from 32 Enterobacteriaceae-type strains and those available in the
      Genbank nucleotide sequence database (n = 24) were used as a database to identify
      240 clinical enterobacteria isolates. Sequence analysis of the gyrBint fragment
      of 240 strains showed that gyrBint constitutes a discriminative target sequence
      to differentiate between Enterobacteriaceae species. Comparison of these
      identifications with those obtained by phenotypic methods (Vitek 1 system and/or
      Rapid ID 32E; bioMerieux, Marcy l'Etoile, France) revealed discrepancies
      essentially with genera Citrobacter and Enterobacter. Most of the strains
      identified as Enterobacter cloacae by phenotypic methods were identified as
      Enterobacter hormaechei strains by gyrBint sequencing. The direct sequencing of
      gyrBint would be useful as a complementary tool in the identification of clinical
      Enterobacteriaceae isolates.

PMID- 16626903
TI  - Mathematical formulation of additivity for antimicrobial agents.
AB  - The ability to describe and quantify pharmacodynamic interaction objectively is
      of paramount importance in the study of combination chemotherapy. Current methods
      based on Loewe additivity and Bliss independence are associated with implicit
      assumptions of the interacting system. We reviewed the hyperplane theorem that
      used a generalized equation for defining the isobols (surfaces of equal effect)
      for 2 noninteracting drugs. We showed that under certain conditions, the original
      equation might lead to nonintuitive results, which were inconsistent with the
      definition of additivity. To circumvent these limitations, an alternative model
      for defining additivity based on effect summation is proposed. This alternative
      definition for isobols deviates from the Loewe additivity, the null interaction
      criterion used as the foundation for Berenbaum's isobol equation. However, its
      results are simple, easily interpreted, and may be more applicable to a wide
      variety of clinical and experimental circumstances.

PMID- 16626904
TI  - In vitro activities of tigecycline against recently isolated Gram-negative
      anaerobic bacteria in Greece, including metronidazole-resistant strains.
AB  - The in vitro activity of tigecycline was compared with those of benzylpenicillin,
      piperacillin + tazobactam, cefoxitin, imipenem, metronidazole, clindamycin, and
      tetracycline against 249 Gram-negative anaerobic bacteria (158 Bacteroides
      fragilis group, 27 non-fragilis Bacteroides spp., 44 Prevotella spp., and 20
      miscellaneous), recently isolated from 8 general hospitals in Athens, Greece.
      Overall tigecycline MIC(50) and MIC(90) were 0.25 and 2 mg/L, respectively,
      whereas B. fragilis group MIC(50) and MIC(90) were 0.5 and 4 mg/L, respectively.
      In total, 93% of the isolates were susceptible to tigecycline (MIC </= 4 mg/L)
      and no high-level resistance (MIC >/= 32 mg/L) was detected. In addition,
      tigecycline exhibited good activity against metronidazole- and tetracycline
      resistant isolates (MIC(90), 0.5 and 8 mg/L, respectively). In summary,
      tigecycline exhibits good in vitro activity against Gram-negative anaerobic
      bacteria isolated in Greece, as well as stability to the most common occurring
      resistance mechanisms, attributes that make this parenteral agent an attractive
      alternative for use against infections involving these microorganisms.

PMID- 16626905
TI  - Septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient
      receiving infliximab therapy.
AB  - We report a case of septic arthritis due to Roseomonas mucosa in a rheumatoid
      arthritis patient receiving infliximab therapy. This is the first report of
      septic arthritis due to R. mucosa, and infliximab therapy might be a predisposing
      factor because this infection was never reported in the pre-anti-tumor necrosis
      factor alpha therapy period.

PMID- 16626906
TI  - Differentiation of tuberculous meningitis from acute bacterial meningitis using
      simple clinical and laboratory parameters.
AB  - Tuberculous meningitis (TBM) is still a major cause of serious illness in many
      parts of the world. The newer diagnostic tests and neuroimaging methods are
      unlikely to be available in many developing countries. We attempt to identify
      simple parameters for early diagnosis. A retrospective study was performed to
      compare the clinical and laboratory features of cultured-confirmed, TBM (134) and
      other bacterial meningitis (709). Features independently predictive of TBM were
      studied by multivariate logistic regression to develop a diagnostic rule. Six
      features were found predictive: length of clinical history >5 days, headache,
      total cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear
      appearance of CSF, lymphocyte proportion of >30%, and protein content of >100
      mg/dL. Application of 3 or more parameters revealed 93% sensitivity and 77%
      specificity. Applying this diagnostic rule can help in the early diagnosis of
      TBM, in both children and adults.

PMID- 16626907
TI  - Determination and geographic distribution of Orientia tsutsugamushi serotypes in
      Thailand by nested polymerase chain reaction.
AB  - Clotted blood samples of 240 scrub typhus patients were collected from 8 Regional
      Medical Sciences Centers in Thailand during 1999 to 2002. The serotypes of
      Orientia tsutsugamushi and their geographic distribution were determined. A
      nested polymerase chain reaction (PCR) was used to identify the serotypes of O.
      tsutsugamushi. The number of patients with positive results for O. tsutsugamushi
      was 25.0%. Two serotypes, Karp and Kato, were detected in these samples. No
      Gilliam serotype was detected from any of the study locations. The PCR products
      were sequenced using an automated DNA sequencer. The nucleotide sequence of gene
      encoding 56-kDa protein from these samples showed a high sequence homology with
      the reference sequence of O. tsutsugamushi Karp and Kato serotypes. O.
      tsutsugamushi Karp serotype was predominant throughout Thailand with the
      percentage of 96.8% of the total serotype-positive patients, whereas 3.2% for
      Kato serotype was observed only in the south. The highest number among the region
      of Karp serotype-positive patients of 31.6% was found in the northeast.

PMID- 16626908
TI  - Stool antigen tests for the detection of Helicobacter pylori in children.
AB  - Stool specimens from 102 children (median age = 6.0 years; Helicobacter pylori in
      biopsy specimens, n = 43) were tested for H. pylori with the monoclonal antibody
      based enzyme immunoassay HpStar. In 28 cases, the specimen was obtained with a
      rectal cotton swab during endoscopy. The sensitivity and specificity of the
      HpStar were 0.95 and 0.90, respectively, as compared with biopsy-based methods.
      The rectal cotton swab specimen gave accurate results in 24 of the 28 cases.
      Storage of specimens for 1, 3, or 7 days (n = 6) had a minor effect on the
      results, but one specimen's originally positive value on borderline turned
      negative when it was kept in room temperature. Forty-eight specimens were tested
      in parallel with all 3 tests used: HpStar, Premium Platinum HpSA, and the rapid
      test ImmunoCardSTAT! The accuracy rates of the tests were 98% for the HpSA and
      HpStar and 96% for the ImmunoCardSTAT! The performance of the stool antigen tests
      was excellent in young children.

PMID- 16626910
TI  - Haemophilus influenzae serotype f purulent pericarditis: a cause of death in a
      child with Down syndrome.
AB  - Purulent pericarditis is a cardiac emergency that can be difficult to diagnose
      and can be rapidly fatal. We report the case of a child with Down syndrome and
      recent atrial and ventricular septal defect repair who died from Haemophilus
      influenzae serotype f pericarditis.

PMID- 16626911
TI  - Rise of Streptococcus pneumoniae isolates containing both erm(B) and mef(E) genes
      from an adult tertiary care community hospital system.
AB  - The emergence of macrolide- and lincosamide-resistant Streptococcus pneumoniae is
      a worldwide concern. Of particular interest is the increasing prevalence of
      erythromycin and clindamycin-resistant isolates containing both erm(B) and mef
      genes. This study determined the prevalence of erythromycin and clindamycin
      resistance in 596 clinical S. pneumoniae isolates from 2 adult tertiary care
      hospitals over a 4-year period (2001-2004). Erythromycin resistance increased
      from 24% to 34%, but S. pneumoniae isolates resistant to clindamycin as well as
      to erythromycin increased from 3% in 2001 to 15.5% in 2004 (5-fold increase).
      Among erythromycin-resistant isolates, those also resistant to clindamycin
      (MLS(B) phenotype) increased 3-fold (12.8-45%). Of forty-one
      erythromycin/clindamycin-resistant S. pneumoniae isolates tested, 29 (71%)
      contained both erm(B) and mef(E) genes. Pulsed-field gel electrophoresis
      performed on 28 erm(B) + mef(E) positive isolates identified 2 predominant and
      possibly related clones, which made up 64% of the isolates.

PMID- 16626912
TI  - Molecular diagnosis of culture-negative cerebral nocardiosis due to Nocardia
      abscessus.
AB  - We describe a case of culture-negative cerebral nocardiosis in a 34-year-old
      immunocompetent man who presented multiple cerebral abscesses. All bacteriologic
      cultures were negative. Nocardiosis was diagnosed by using a direct genus
      specific 16S rDNA amplification method, and Nocardia abscessus was identified by
      hsp65 sequence analysis. The patient is alive and well on imipenem and
      doxycycline therapy, 14 months after onset.

PMID- 16626913
TI  - Salmonella enterica serovar Enteritidis producing a TEM-52 beta-lactamase: first
      report in Spain.
AB  - TEM-52 is an extended-spectrum beta-lactamase (ESBL) that is being increasingly
      reported in enterobacteria. In Spain, TEM-52 had been reported before only in
      Escherichia coli. Here we report the first finding of a TEM-52 ESBL in Salmonella
      in Spain, associated to a Tn3 transposon.

PMID- 16626914
TI  - Quantitative detection of Streptococcus pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis in lower respiratory tract samples by real-time PCR.
AB  - The limitation of polymerase chain reaction (PCR) in diagnosis of lower
      respiratory tract infections (LRTIs) caused by Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis has been a distinguishing
      colonization from infection. We assess here the usefulness of real-time
      quantitative PCR (RQ-PCR) performed on lower respiratory tract samples to
      overcome this problem. Consecutive respiratory tract samples from patients with
      and without signs of infection (n = 203) were subjected to RQ-PCR, targeting the
      genes pneumolysin (S. pneumoniae), fumarate reductase (H. influenzae), and outer
      membrane protein B (M . catarrhalis). DNA from positive controls with predefined
      colony forming units (CFUs) per milliliter were included to allow estimation of
      CFU per milliliter for the test samples. In parallel, assessment of quantitative
      cultures from all samples was performed. In the group of patients with LRTI,
      significant pathogens (>/=10(5) CFU/mL) were found in 32/135 samples (23.7%) with
      culture, in 51/135 (37.7%) with RQ-PCR, and in 59/135 (43.7%) when combining the
      methods.

PMID- 16626915
TI  - Clinical suspicion as a primary guidance to use commercial amplification tests
      for rapid diagnosis of pulmonary tuberculosis.

PMID- 16626916
TI  - Recombinant antigens as diagnostic markers for aspergillosis.
AB  - Eight recombinant proteins and purified galactomannan of Aspergillus fumigatus
      were tested by enzyme-linked immunosorbent assay to quantify the anti-Aspergillus
      antibodies in sera of patients with aspergilloma, allergic bronchopulmonary
      aspergillosis (ABPA), and invasive aspergillosis (IA). In spite of the
      variability observed in the immune responses of individual patients,
      quantification of the antibody titers against the 18-kDa ribonuclease (RNU), the
      360-kDa catalase (CAT), and the 88-kDa dipeptidylpeptidase V (DPPV) was useful
      for the diagnosis of aspergilloma and ABPA. Differential diagnosis of ABPA was
      even possible among cystic fibrosis as well as noncystic fibrosis patients. In
      the group of immunocompromised patients with IA, no antibody response was mounted
      in response to the Aspergillus infection in any of the patients. Interestingly,
      about half of the patients with proven IA came to the hospital with high titers
      of anti-Aspergillus antibodies, suggesting that they were infected upon entry to
      the hospital. These results suggest that recombinant RNU, CAT, and DPPV have a
      great potential in the serodiagnosis of all forms of aspergillosis in the
      immunocompromised and immunocompetent patient.

PMID- 16626917
TI  - Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell
      transplant patients receiving voriconazole prophylaxis.
AB  - We performed a retrospective observational study to examine the incidence of
      invasive aspergillosis (IA) among allogeneic hematopoietic stem cell transplant
      (HSCT) recipients, according to whether patients received at least 1 week of
      voriconazole prophylaxis. We report no cases of IA among 92 HSCT recipients who
      received voriconazole prophylaxis compared with a 10% (23/223) incidence among
      those receiving other systemic antifungals for prophylaxis (P < .0005).

PMID- 16626918
TI  - An improved selective and differential medium for the isolation of Burkholderia
      pseudomallei from clinical specimens.
AB  - Isolation and culture of Burkholderia pseudomallei remains the main stay in the
      diagnosis of melioidosis. Thus, the search for selective and differential media
      for B. pseudomallei has been ongoing. A number of such media have been reported
      with varying efficacy. Ashdown medium is the most established selective medium
      for the isolation of B. pseudomallei. There are no reports of differential media
      differentiating B. pseudomallei from Burkholderia cepacia. This report documents
      such a selective and differentiating medium for B. pseudomallei. Of a total of
      1042 clinical specimens containing mixed flora and gram-negative isolates that
      were tested on this medium, 16 of the specimens yielded B. pseudomallei. The
      isolation rate was found to be 1.5%. This medium was found to be simple and
      inexpensive, can be made by small laboratories, and called as Francis medium.
      Based on the colony morphology and color, a preliminary report can be made within
      18-24 h for the presence of B. pseudomallei. Our study showed that this medium
      had an overall sensitivity of 78.4% with a specificity of 92.2%. The use of this
      medium as an early diagnostic tool will help to reduce mortality and morbidity of
      melioidosis patients.

PMID- 16626919
TI  - Seasonal and photoperiodic regulation of secretion of hormones associated with
      reproduction in Magang goose ganders.
AB  - This study examined the reproductive endocrine profile under natural and
      artificial photoperiods in Magang goose ganders. Group 1 ganders (n=8) served as
      non-treated controls and were exposed to natural photoperiod throughout the
      experiment from 13th January to 17th December 2004. Group 2 ganders (n=8) were
      exposed to 18 h long daily photoperiod for 60 days from 13 January till 15 March
      2004 and again to 16 h photoperiod for 75 days till 10th October 2004, and the
      11h short photoperiod in the remainder periods of the experiment. In control
      ganders, plasma LH concentrations were high in normal breeding seasons (August
      March) and decreased to low levels in non-breeding season from April to July.
      Testosterone concentrations changed similarly to that of LH throughout the
      seasons. Seasonal pattern of PRL concentrations was opposite to those of LH and
      testosterone, with low values in breeding season and high values in non-breeding
      season. In artificial photoperiod treated ganders, increasing photoperiod
      increased PRL and decreased LH and testosterone concentrations, while decreasing
      photoperiod reversed these changes. There were no seasonal or photoperiod caused
      changes in plasma T3 concentrations in both control ganders and artificial
      photoperiod treated ganders. These results demonstrated that in Magang goose
      ganders that long photoperiod stimulates PRL secretion and decreases LH
      secretion, which terminates reproductive season in spring and early summer, and
      short photoperiod stimulates LH secretion and inhibits PRL secretion rendering
      ganders enter into reproductive season.

PMID- 16626920
TI  - Thromboprophylaxis in major abdominal surgery for cancer.
AB  - AIMS: To review the epidemiology and pathogenesis of venous thromboembolism (VTE)
      in surgical cancer patients, in addition to the use of thromboprophylaxis in
      major abdominal surgery, such as low-molecular-weight heparin (LMWH) and
      fondaparinux. METHODS: Systematic review of the literature, focussing on risk
      factors for VTE, parenteral methods of thromboprophylaxis, approaches to
      prolonged prophylaxis, and effects on patient survival. FINDINGS: Patients with
      cancer undergoing abdominal surgery are at substantially higher risk for VTE than
      patients without cancer. Furthermore, prolonged thromboprophylaxis for up to 4
      weeks is more effective than short-term administration in these high-risk
      patients. The concurrent use of graduated compression stockings has a synergistic
      effect on the reduction in VTE risk. CONCLUSIONS: Thromboprophylaxis with LMWH
      has been shown to minimise the incidence of thromboembolic events, and is a well
      established therapy worldwide. The American College of Chest Physicians
      recommends the routine use of thromboprophylaxis, with LMWH or unfractionated
      heparin, in patients with cancer who are undergoing surgical procedures, and the
      appropriate use of these thromboprophylactic agents has significant implications
      for the clinical care and quality of life of surgical patients with cancer.

PMID- 16626921
TI  - Verrucous carcinoma of the larynx: determining the best treatment option.
AB  - BACKGROUND: Verrucous carcinoma (VC) of the larynx is a rare variant of well
      differentiated squamous cell carcinoma, characterized by locally invasive,
      exophytic warty growth. The purpose of the present study was to evaluate the
      experience with this rare disease in Slovenia over a 23-year period and to weigh
      the potential for cure of different treatment options against the functional
      outcome. MATERIALS AND METHODS: The databases of the Cancer Registry of Slovenia
      as well as of the registries of all three departments licensed for the treatment
      of laryngeal cancer in the country were used for the identification of patients.
      Presentation, diagnosis, treatment and outcome were reviewed retrospectively.
      RESULTS: From 1980 to 2002, 30 patients were diagnosed with VC of the larynx,
      representing 1.23% of all laryngeal malignancies. The most frequent site of
      origin was the glottis. Twenty-three patients had surgery (functional 13; total
      laryngectomy 10), three patients had radiotherapy, and a combination of
      irradiation and concomitant chemotherapy was used in four patients. Only one
      tumor recurred, six months after primary radiation treatment, but was
      successfully salvaged with a total laryngectomy. The 5-year overall survival rate
      of 75% was not significantly different from an age- and sex-matched cohort from
      the Slovenian population (P=0.071). CONCLUSIONS: In VC of the larynx,
      determination of treatment options should be dictated by voice preservation
      strategies. Surgery remains the gold standard of treatment. However, concomitant
      radiochemotherapy emerges as an attractive alternative to mutilating surgical
      procedures.

PMID- 16626922
TI  - Radioactivity thresholds for sentinel node biopsy in breast cancer.
AB  - AIMS: The aim of the present study is to clarify the level of radioactive lymph
      node should be biopsied after the most radioactive SN is removed. METHODS: SNB
      using radionuclide was performed in our hospital for 1179 primary breast cancers
      between April 2000 and October 2005; most (1177/1179) were performed
      successfully. Our criterion for harvesting SNs is to remove tissue until no
      radioactive site is present. The level of radioactivity and the order of removal
      of each lymph node were compared with pathologic results. RESULTS: More than 2
      (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts.
      Cancer positive results were recorded for 142 breasts with multiple SNs. In 142
      breasts, 64 showed metastasis to the most radioactive node only, 39 showed
      metastasis other than the most radioactive node only, and 39 showed the most
      radioactive node and other radioactive nodes. Moreover, if several other criteria
      were applied, false-positive cases were increased significantly. CONCLUSIONS: It
      is necessary to harvest radioactive lymph nodes other than the most radioactive.
      Moreover, efforts to remove every radioactive lymph node will minimize false
      negative results.

PMID- 16626923
TI  - Malignancies following bilateral salpingo-oophorectomy (BSO).
AB  - AIMS: Prophylactic bilateral salpingo-oophorectomy (BSO) is an effective risk
      reducing measure in ovarian cancer susceptible women. Yet, a small subset of
      women develop primary peritoneal carcinomatosis (PPC) after BSO. The rates of PPC
      following non-risk reducing BSO have sparingly been reported. METHODS: Women who
      underwent BSO for non-cancer reasons from 1/1/1984 to 12/31/2000 were crossed
      with the list of cancer diagnoses reported to the Israel National Cancer Registry
      until 12/31/2001. RESULTS: Overall, 4128 women at a mean age of 58+/-12 years
      were analyzed. After a mean of 7.2+/-4 years following BSO, 147 women (3.6%) were
      diagnosed with cancer: breast cancer in 50 women 62+/-50 months after BSO, and
      one patient developed PPC, whereas the expected was 0.15 cases. The Standardized
      Incidence Ratio (SIR) of developing breast cancer was statistically significant
      lower than expected (SIR 0.71, 95% C.I. 0.44-0.78). CONCLUSION: The rate of post
      oophorectomy PPC in average risk population is low, and BSO appears to lower the
      rate of breast cancer in average risk women.

PMID- 16626924
TI  - [Candiduria in intensive care unit: significance and value of yeast numeration in
      urine].
AB  - JUSTIFICATION: Candiduria is increasingly frequent among patients admitted to
      intensive care units but its significance remains unclear. OBJECTIVES: Search for
      eventual correlation between quantitative candiduria and known risk factors for
      invasive candidiasis. STUDY DESIGN: Prospective. PATIENTS AND METHODS: A four
      month study was conducted in 162 patients hospitalized in the intensive care unit
      for more than 72 hours. All patients underwent a weekly research of candiduria
      added to sampling from different body sites to determine the Pittet Candida
      colonization index. RESULTS: Candiduria has been proved in 56 cases (34%). It was
      superior or equal to 10(4) UFC/ml among 28 patients (50%). Candida tropicalis,
      Candida glabrata and Candida albicans has been isolated in 41, 22 and 20%
      respectively. All patients had at least one major and two minor risk factors for
      Candida infection. Six patients (10%) developed invasive candidiasis. The global
      mortality rate was at 52%. Pittet colonization index was significantly different
      between patients with candiduria and those with invasive candidiasis (p=0.01).
      There was a statistically significant correlation between candiduria superior or
      equal to 10(4) UFC/ml and Pittet colonization index superior or equal to 0.5
      (p=0.01). CONCLUSION: Candiduria superior or equal to 10(4) UFC/ml associated
      with risk factors may predict invasive candidiasis in critically ill patients.

PMID- 16626925
TI  - [Patient-controlled epidural analgesia for labour: in practice].
AB  - OBJECTIVES: Update on patient controlled epidural analgesia for labour. STUDY
      DESIGN: Literature review of the recent data on local anaesthetics, additional
      analgesics and of publications on the various protocols used. DATA COLLECTION:
      Pubmed database was checked with the following key words: PCEA, labour, opioids,
      clonidine. The abstracts of the ASA meetings from 2000 to 2005 were also
      examined. RESULTS: Patient controlled epidural analgesia (PCEA) is the method of
      choice for optimal labour pain management. The advantages of this technique are
      numerous. Some of them are established: consistent reduction in overall local
      anathetic requirement, less motor blockade, safety of the technique and team
      workload reduction. A better adequacy with the analgesic requirements and an
      increase in overall patient satisfaction are frequently retrieved, provided that
      the choice of the analgesics and the PCEA parameters are adequately chosen.
      CONCLUSION: The use of PCEA improves the quality of analgesic management offered
      to the parturients who are more and more willing to have a "more natural"
      childbirth. The PCEA gives them more autonomy and, in fine, enables them to
      better enjoy this unique event. The main barrier to a more widespread diffusion
      of PCEA in many institutions remains the financial issue, although a well
      selected device and low cost disposables allow a reduction of indirect costs by
      decreasing care giver workload.

PMID- 16626926
TI  - Evidence for cross-regulated cytokine response in human peripheral blood
      mononuclear cells exposed to whole gonococcal bacteria in vitro.
AB  - Neisseria gonorrhoeae is an obligate human pathogen that represents a significant
      health concern, particularly in the developing world. Although generally
      associated with an acute inflammatory infection of urogenital epithelia cells,
      infections have been noted in multiple tissues and many infected individuals can
      become asymptomatic carriers. Few studies of immune response to N. gonorrhoeae
      infection in peripheral blood have evaluated the production of T helper cytokines
      (TH1/TH2) induced early after infection. We developed a quantitative realtime PCR
      assay based on the gonococcal rmpIII gene to monitor dose-response effects of
      infection on cytokine release from peripheral blood mononuclear cells (PBMCs). We
      observed upregulation of CD69 transcription and surface CD25 expression on
      lymphocytes, consistent with early T-cell activation. We observed dosage
      dependent transcription of the chemotactic factor IL-8 and previously unreported
      activation of the chemoattractant MCP-2. Multiplex analysis of broad cytokine
      protein production revealed a differential increase in the TH1 and TH2 associated
      cytokines: IL-2, IL-4, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha and MCP-1. Markov
      models of protein accumulation implicated a cross-regulated response to
      infection, notably for IL-8, IL-10 and IL-12. Taken together, the cytokine
      profile we observed early in response to whole gonococcal bacteria was broader
      than has been previously described and may have relevance for the contribution of
      antagonistic signaling events early in infection and in understanding peripheral
      immune mechanisms engaged to control infection.

PMID- 16626927
TI  - The Ser/Thr kinase activity of the Yersinia protein kinase A (YpkA) is necessary
      for full virulence in the mouse, mollifying phagocytes, and disrupting the
      eukaryotic cytoskeleton.
AB  - The Yersinia protein kinase A (YpkA) is injected into host cells by the yersinial
      type three secretion system (TTSS). YpkA is widely believed to function within
      the host cell based on the fact that its kinase domain is clearly homologous to
      eukaryotic Ser/Thr kinases and that its enzymatic activity, when assayed in
      vitro, is dependent on eukaryotic-derived host factors. Whether this activity is
      required for virulence has not been addressed. Here, we report that a Yersinia
      pseudotuberculosis strain expressing a kinase-inactive YpkA(D270A) variant is
      greatly attenuated in the mouse model of infection compared to the isogenic wild
      type strain. The ypkA(D270A) mutant strain was likewise attenuated in a cell
      culture infection assay indicating that the kinase activity of YpkA enhances the
      viability of host cell-associated bacteria. To begin to understand what cellular
      activities are targeted, we expressed YpkA and its variants in two different
      yeast model systems. In agreement with previous studies, we found that when
      rapidly induced and expressed at high levels in Saccharomyces cerevisiae, YpkA
      mediated toxicity occurred extremely swiftly. Under these conditions toxicity was
      dependent on the structurally distinct GTPase-binding domain of YpkA and was
      entirely independent of its kinase activity. Therefore, to probe for kinase
      dependent effects we expressed YpkA and its kinase-inactive variant at
      comparatively moderate levels in the fission yeast Schizosaccharomyces pombe. S.
      pombe is particularly well suited for actin cytoskeletal studies due to its
      easily quantifiable, well defined pattern of actin localization. S. pombe
      transformed with a wild-type YpkA-encoding plasmid displayed a pronounced actin
      mislocalization phenotype, the severity of which was directly proportional to the
      level of YpkA expressed in the cell. In cells expressing the kinase-inactive YpkA
      variant, the degree of actin mislocalization was reduced, but not entirely
      abrogated, suggesting that YpkA affects the eukaryotic cytoskeleton through
      kinase-dependent and kinase-independent mechanisms. Collectively, our yeast
      derived results show how critical expression levels and exposure periods are for
      assaying virulence factor activities in heterologous model systems. More
      generally, our finding that the 'eukaryotic-like' kinase domain of YpkA is
      important for virulence illustrates how a bacterium can utilize a host-like
      factor or activity in order to enhance its survival following host cell contact.

PMID- 16626928
TI  - Development of a novel three-dimensional in vitro model of oral Candida
      infection.
AB  - Oropharyngeal candidiasis is emerging as a serious health problem in the elderly
      as well as other chronically immunosuppressed patient populations. Several
      approaches have been used to study the interactions between Candida and the oral
      mucosa in vitro. Recently, three-dimensional organotypic systems of the oral
      mucosa have been developed, which provide an organizational complexity that is
      between the culture of single cell types and organ cultures in vivo. In this
      report we describe the development of a novel three-dimensional system of the
      human oral mucosa based on an immortalized oral keratinocyte cell line. Unlike
      the commercially available cell line systems, this system also contains a
      connective tissue cell component, which ensures the quality and resemblance of
      the tissue model to the human oral masticatory mucosa and submucosa. Using a
      panel of Candida albicans strains with variable virulence in vivo, we showed that
      the extent of tissue damage, fungal invasion and host inflammatory response in
      this system was proportional to the well-documented in vivo virulence potential
      of these strains. Therefore, this investigation has added another useful tool in
      the study of host pathogen interactions in oral candidiasis.

PMID- 16626929
TI  - Mycobacterial sulfolipid shows a virulence by inhibiting cord factor induced
      granuloma formation and TNF-alpha release.
AB  - Virulence mechanism of infection with Mycobacterium tuberculosis is currently
      focused to be clarified in the context of cell surface lipid molecule. Comparing
      two mycobacterial glycolipids, we observed toxicity and prominent
      granulomatogenic activity of trehalose 6,6'-dimycolate (TDM) injection in mice,
      evident by delayed body weight gain and histological observations, whereas
      2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL) was non-toxic and non
      granulomatogenic. Likewise, TDM but not SL caused temporarily, but marked
      increase of lung indices, indicative of massive granuloma formation.
      Interestingly, co-administration of TDM and SL prevented these symptoms
      distinctively and SL inhibited TDM-induced release of tumor necrosis factor alpha
      (TNF-alpha) in a dose-dependent manner. Histological findings and organ index
      changes also showed marked inhibition of TDM induced granuloma formation by co
      administration of SL. Simultaneous injection of SL together with TDM was highly
      effective for this protection, as neither injection 1h before nor after TDM
      injection showed highly inhibitory. In parallel studies on a cellular level, TDM
      elicited strong TNF-alpha release from alveolar but not from peritoneal
      macrophages in vitro. This effect was blocked when alveolar macrophages were
      incubated in wells simultaneously coated with TDM and SL, indicating that SL
      suppresses TDM-induced TNF-alpha release from macrophages. Our results suggest a
      novel mechanism by which SL could contribute to virulence at early stage of
      mycobacterial infection or stimulation with the glycolipids by counteracting the
      immunopotentiating effect of TDM.

PMID- 16626930
TI  - The major circulating immunosuppressive activity in American visceral
      leishmaniasis patients is associated with a high-molecular weight fraction and is
      not mediated by IgG, IgG immune complexes or lipoproteins.
AB  - Opportunistic infections, due to disease-related immunosuppression, constitute
      the major cause of death in American visceral leishmaniasis (AVL). Sera from
      these patients (AVL sera) non-specifically inhibit the in vitro proliferative
      response of normal human lymphocytes to lectins or antigens. In the present work,
      the mediation of this inhibition by IgG, immune complexes and low- or very low
      density lipoproteins was studied. AVL serum fractions containing proteins with
      the molecular weight of IgG, and IgG, purified from AVL sera by anion exchange
      chromatography, did not suppress the lymphoproliferation. Most of the suppressive
      activity of AVL sera was associated with a fraction containing molecules with
      molecular weights above 430 kDa. This would be compatible with it being due to
      immune complexes and/or lipoproteins, and not to soluble IL-2 receptors as
      reported previously. However, neither of the two possibilities seem to be the
      case, as (1) depletion of immune complexes by protein-A followed by protein-G
      chromatographies did not affect the serum suppressive activity, (2) no
      correlation between immune complex contents and suppressive activities in
      individual sera was observed, and (3) plasma lipoproteins (VLDL and LDL),
      purified from AVL patients and from healthy individuals, had the same degree of
      immunosuppressive activity.

PMID- 16626931
TI  - Deletion of the genes encoding the type III secretion system and cytotoxic
      enterotoxin alters host responses to Aeromonas hydrophila infection.
AB  - In our previous study, we deleted the gene encoding Aeromonas outer membrane
      protein B (AopB), a structural component of the type III secretion system (T3SS)
      from a cytotoxic enterotoxin gene (act)-minus diarrheal isolate SSU of Aeromonas
      hydrophila. Our laboratory also molecularly characterized the cytotoxic
      enterotoxin (Act), which is secreted by the bacterium utilizing the type II
      secretion system (T2SS). The act/aopB mutant exhibited significantly reduced
      cytotoxicity to cultured cells (e.g. RAW 264.7 murine macrophages and HT-29 human
      colonic epithelial cells) and was avirulent in mice. In this study, we developed
      additional A. hydrophila mutants in which T3SS-associated ascV and acrV genes
      were deleted, either individually or in combination with that of the act gene, to
      examine host-pathogen interactions. A significant reduction in the induction of
      inflammatory cytokines and chemokines was noted in the sera of mice infected with
      these mutants when compared to animals infected with wild-type (WT) A.
      hydrophila. After infection with the WT and act/aopB mutant, we performed
      microarray analyses on RNA from the above-mentioned murine macrophages and human
      colonic epithelial cells to examine global cellular transcriptional responses.
      Based on three independent experiments, WT A. hydrophila altered the expression
      of 434 genes in RAW 264.7 cells and 80 genes in HT-29 cells. Alteration in the
      expression of 209 macrophage and 32 epithelial cell genes was reduced when the
      act/aopB mutant was used, compared to when cells were infected with the WT
      bacterium, indicating the involvement of Act and/or AopB in transcriptional
      regulation of these genes. We verified up-regulation of 15 genes by real-time
      reverse transcriptase-polymerase chain reaction and confirmed A. hydrophila WT
      versus mutant-induced production of cytokines/chemokines in supernatants from RAW
      264.7 and HT-29 cells. This is the first description of host cell transcriptional
      responses to A. hydrophila infection.

PMID- 16626932
TI  - Tspy is nonfunctional in the Mongolian gerbil but functional in the Syrian
      hamster.
AB  - The TSPY gene is conserved in placental mammals and encodes the testis-specific
      protein, Y encoded. Within the testis, TSPY expression is restricted to germ
      cells, and it is assumed that TSPY plays a role in the proliferation of germ
      cells. Since it was first discovered in humans, TSPY orthologous gene families
      have been subsequently characterized in many mammalian lineages. In contrast to
      the situation in cattle and primates, in which TSPY is organized in a moderately
      repetitive cluster, including functional members and pseudogenes, a peculiar
      situation is observed in rodents, in which Tspy has been become low or single
      copy and degenerated to a pseudogene in some species of the subgenus Mus. We have
      extended this approach and investigated Tspy gene evolution in the Syrian hamster
      (Mesocricetus auratus) and the Mongolian gerbil (Meriones unguiculatus). Whereas
      the Syrian hamster Tspy is functionally conserved, organized in multiple copies,
      and expressed only in testis, the closely related Mongolian gerbil possesses a
      single-copy pseudogene that is unable to generate a functional transcript. Thus,
      the Tspy locus has degenerated at least twice at different points of rodent
      evolution, strongly supporting the hypothesis that the decay of Y-chromosomal
      genes is an intrinsic evolutionary process. TSPY is the first example of a Y
      chromosomal tandem repetitive gene whose decay could be studied in two
      independent mammalian lineages.

PMID- 16626933
TI  - Laryngostroboscopic evaluation after supracricoid partial laryngectomy.
AB  - BACKGROUND: Supracricoid partial laryngectomy (SCPL) results in laryngeal
      preservation in more than 95% of patients with T2 glottic carcinoma. Postsurgical
      glottic function is characterized by an absence of vocal cords, and phonation
      quality is a key post-SCPL quality-of-life factor. OBJECTIVE: This investigation
      was designed to enhance post-SCPL vocal function, study anatomic function of the
      post-SCPL larynx, and correlate anatomic findings with perceptual and
      instrumented measurements of voice. METHOD: Twenty-five patients were included.
      All had undergone SCPL with cricoepiglottopexy for T2 glottic carcinoma. All
      patients were evaluated by laryngostroboscopic examination, voice sample
      recording, and instrumented voice analysis with the aim of gaining further
      insight into postoperative larynx function. Laryngostroboscopic parameters such
      as laryngeal occlusion, epiglottic length, arytenoid movement, and vibratory area
      were assessed. The perceptual evaluation was based on the GRBAS scale. Acoustic
      and aerodynamic parameters were recorded, including fundamental frequency (F0),
      intensity, jitter, shimmer, signal-to-noise ratio (SNR), oral airflow (OAF),
      maximum phonation time (MPT), and estimated subglottic pressure (ESGP).
      Nonparametric tests were used to compare laryngostroboscopic parameters with
      instrumented measurements and perceptual evaluations of voice quality. RESULTS:
      Correlations were established among occlusion, epiglottic length, and general
      grade of dysphonia. Oral air flow (P = 0.006) was found to be correlated with
      occlusion. Voice roughness was correlated with the presence of a clearly
      identifiable vibratory area (P = 0.003), whereas these vibratory areas were
      correlated with shimmer (P = 0.041), OAF (P = 0.001), and SNR (P = 0.001). The
      number of preserved arytenoids was not identified as a voice quality factor (P =
      0.423). CONCLUSION: This study highlighted correlations between the
      laryngostroboscopic examination results and the perceptive and instrumented
      measurements of voice. Glottis occlusion and epiglottis length were found to be
      key factors for postoperative voice quality. These results should help to advance
      technical development on surgical techniques to enhance voice results.

PMID- 16626934
TI  - Musculoskeletal patterns in patients with voice disorders.
AB  - This study correlated the ear, nose, and throat (ENT) and physiotherapy input on
      26 patients who presented with voice problems and were found by the ENT surgeon
      to have a degree of musculoskeletal issues. It also looked for patterns of
      musculoskeletal findings. Although all patients referred were found by the
      physiotherapist to have musculoskeletal abnormalities, the correlation proved to
      be excellent among the subgroup of performers, but only fair-to-good among the
      other voice professionals. Certain patterns of musculoskeletal abnormalities were
      frequently encountered, including a high held larynx, a shortening or contraction
      of the stylohyoid and sternocleidomastoid muscles, and a weak deep flexor
      mechanism. In this small group, most patients seemed to improve, although it must
      be noted that management was not limited to physiotherapy. In summary,
      physiotherapy input proved helpful in the evaluation and management of this group
      of patients presenting with voice problems.

PMID- 16626935
TI  - Frequency and voice: perspectives in the time domain.
AB  - SUMMARY: Frequency variation is one of the most primitive features of voice
      production, endowing language and communication with richness and efficiency and
      enhancing enjoyment of the voice arts. In the first of two tutorial articles, the
      subject of frequency is examined formally, beginning in the time domain. A
      companion article explores the topic of frequency and voice from the frequency
      domain perspective. Frequency is a well-defined quantity of the sinusoidal
      function and of periodic functions of time. However, voice is inherently
      nonstationary, even over short time segments, to degrees that range from minor
      (stable vowels of a healthy voice) to major (singing voice and voiced
      consonants). For signals that are not periodic, the notion of frequency is
      ambiguous and often altogether unclear, which has led to a multitude of frequency
      measurement techniques and discrepancy of measures. This article identifies the
      source of these discrepancies for a variety of time-domain techniques that are
      examined in the absence of noise. In the time domain, the subject of frequency is
      inherently coupled to the topic of signal modeling, which is explored in some
      detail. Sinusoidal models having time-varying phase are examined with the
      objective of achieving a frequency description of voice that is both continuous
      and instantaneous. The analytic signal method of mathematical physics is
      discussed and applied to the technology of empirical mode decomposition to
      demonstrate that the frequencies of voice may be comprehensively examined from
      the time domain point of view.

PMID- 16626936
TI  - Sensing extracellular matrix: an update on discoidin domain receptor function.
AB  - Discoidin Domain Receptors (DDRs) have recently emerged as non-integrin-type
      receptors for collagen. The two mammalian gene products Discoidin Domain Receptor
      1 and -2 constitute a subfamily of tyrosine kinase receptors that are selectively
      expressed in a number of different cell types and organs. Upon collagen
      activation, DDRs regulate cell adhesion, proliferation and extracellular matrix
      remodeling. Here we review the various signaling pathways and cellular responses
      evoked by activated DDRs. Additionally, we give an overview of the more recent
      advances in understanding the role of DDRs in various human diseases, in
      particular during tumor progression, atherosclerosis, inflammation and tissue
      fibrosis. Furthermore, we discuss potential roles of genes homologous to
      mammalian DDRs identified in flies, worms and sponges. We show that the
      structural organization of these DDR-related genes is highly conserved throughout
      evolution suggesting that invertebrate DDRs may also function as receptors for
      collagen. By highlighting current questions about these unusual collagen
      receptors, we hope to attract new research on DDRs from a variety of different
      fields.

PMID- 16626937
TI  - Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines.
AB  - INTRODUCTION: The aim of this study was to investigate whether there is an
      increased susceptibility to apoptosis in cultured fibroblasts from patients with
      schizophrenia. METHOD: Dermal fibroblasts were collected and cultured from three
      groups: patients with schizophrenia, patients with non-schizophrenic psychosis,
      and healthy comparison subjects. Susceptibility to apoptosis was measured at the
      level of degradation product (proportion of cells in the sub-G0 cell cycle
      fraction in which apoptotic bodies accumulate), pro-apoptotic effector (activated
      caspase-3), and molecular regulators (P53, Bax and Bcl-2). Cell lines were
      studied under both basal culture and cycloheximide (an apoptotic inducer)
      exposure conditions. RESULTS: Consistent with increased susceptibility to
      apoptosis, the proportion of sub-G0 cells under basal conditions was
      significantly larger in the schizophrenia group, compared to the non
      schizophrenic psychosis group. However when apoptosis was stimulated with
      cycloheximide, the schizophrenia group showed an attenuated caspase-3 response.
      The pattern of correlations between regulators, caspase-3 and the proportion of
      sub-G0 cells was different in the schizophrenia group, consistent with group
      specific apoptotic pathway dysregulation. CONCLUSION: The study demonstrated
      anomalous apoptotic mechanisms in schizophrenia, which appear not to affect non
      schizophrenia psychosis patients. The detection of these anomalies in fibroblasts
      suggests that altered apoptosis may be observable in all somatic cell types in
      schizophrenia.

PMID- 16626938
TI  - Optimization of a multinomial model for investigating hallucinations and
      delusions with source monitoring.
AB  - Studies of source monitoring have played an important role in cognitive
      investigations of the inner/outer confusions that characterize hallucinations and
      delusions in schizophrenia, and multinomial modelling is a statistical/cognitive
      modelling technique that provides a powerful method for analyzing source
      monitoring data. The purpose of the current work is to describe how multinomial
      models can be optimized to answer direct questions about hallucinations and
      delusions in schizophrenia research. To demonstrate this, we present a reanalysis
      of previously published source monitoring data, comparing a group of patients
      with schneiderian first rank symptoms to a group without schneiderian first rank
      symptoms. The main findings of this analysis were (1) impaired recognition of
      self-generated items and (2) evidence that impaired source discrimination of
      perceived items is accompanied by an internalization bias in the target symptom
      group. Statistical and cognitive interpretations of the findings are discussed.

PMID- 16626939
TI  - Are females at special risk of obesity if they become psychotic? The longitudinal
      Northern Finland 1966 Birth Cohort Study.
AB  - Obesity is a serious health problem, especially in patients with long-term mental
      disorders. We explored the socio-demographic, psychiatric, and clinical factors
      that increase the risk of changing from under- or normal weight in adolescence to
      overweight/obese in adulthood. We found a 3.6-fold risk of weight gain in females
      with psychotic disorder. Other significant correlates of weight gain in males
      were physical inactivity, unhealthy diet, high alcohol consumption, and being
      single; and in females, chronic diseases, physical inactivity, high alcohol
      consumption, and having at least three children. These findings emphasize the
      importance of regular weight monitoring in clinical practice, especially in
      females with psychotic disorders.

PMID- 16626940
TI  - Risk factors for completed suicide in schizophrenia and other chronic psychotic
      disorders: a case-control study.
AB  - OBJECTIVE: Despite an increased risk for suicide among individuals diagnosed with
      psychotic disorders, risk factors for completed suicide remain largely unexamined
      in this population. Using a case-control design, this study aimed to investigate
      clinical and behavioural risk factors for suicide completion in schizophrenia and
      other chronic psychotic disorders. METHOD: A total of 81 psychotic subjects were
      examined; of these, 45 died by suicide. Proxy-based interviews with, on average,
      2 informants were conducted using the SCID I and II interviews and a series of
      personality trait assessments. RESULTS: Psychotic individuals at risk for suicide
      are most readily identified by the presence of depressive disorders NOS, moderate
      to severe psychotic symptoms and a family history of suicidal behaviour. They
      also exhibited fewer negative symptoms, had more comorbid diagnoses and, contrary
      to findings in other populations, we found that cluster A and C personality trait
      symptoms seem to have protective effects against suicide in schizophrenics and
      other chronic psychotic suicides. CONCLUSIONS: Our study suggests that
      behavioural mediators of suicide risk, such as impulsive-aggressive behaviours,
      do not play a role in schizophrenic and chronic psychotic suicide. This is
      contrary to findings in other diagnostic groups, thus implying heterogeneity in
      predisposing mechanisms involved in suicide.

PMID- 16626941
TI  - Premorbid intra-individual variability in intellectual performance and risk for
      schizophrenia: a population-based study.
AB  - BACKGROUND: Some, but not most, schizophrenia patients have below-average
      intelligence years before they manifest psychosis. However, it is not clear if
      those whose intelligence falls within-normal-range nevertheless have cognitive
      abnormalities. We examined the association between intra-individual variability
      in intellectual performance and risk for schizophrenia in individuals with normal
      IQ. METHODS: 555,326 adolescents, mandatory assessed by the Israeli Draft Board
      were followed up over 8 to 17 years for psychiatric hospitalization by means of
      the Israeli National Psychiatric Hospitalization Case Registry. Data were
      available on 4 intelligence sub-tests, and on behavioral and psychosocial
      variables. Variability was computed from the variance of the four intelligence
      tests' standardized scores. RESULTS: There was a significant monotonic
      association between increased intra-individual variability in intellectual
      performance and risk of schizophrenia in individuals with within-normal-range IQ.
      Individuals with the highest variability were 3.8 times more likely to have
      schizophrenia [95%CI: 2.32-6.08; p < 0.0001] compared with individuals with the
      lowest variability. This association held after controlling for the effects of
      potential confounders. CONCLUSIONS: Despite within-normal-range premorbid IQ,
      apparently healthy adolescents who will later on manifest schizophrenia,
      nevertheless have cognitive abnormalities such as increased variability across
      intellectual tasks, possibly related to frontal lobe abnormalities.

PMID- 16626942
TI  - Scotopic sensitivity in schizophrenia.
AB  - Among participants with schizophrenia there is evidence for early-stage visual
      processing deficits, which may arise in the rod pathways. Input to the earliest
      level of this pathway, however, has not been tested in this population. It has
      been widely hypothesized that schizophrenia participants have magnocellular
      deficits that occur at the pre-cortical level. To address this hypothesis, we
      studied absolute scotopic (dark-adapted) sensitivity in fifteen schizophrenia and
      fifteen matched control participants. Scotopic thresholds were assessed using a
      1.85-deg, 510-nm circular test stimulus located at 10 degrees eccentricity in the
      left visual field and presented in Maxwellian-view. Thresholds were obtained
      using a two-alternative forced-choice paradigm (an average of 200 trials per
      participant was obtained). Threshold estimates were derived using probit
      analysis. In this procedure the transformed binomial data (the inverse of the
      normal probability integral) is fit with a weighted linear regression. Noise was
      defined as the average deviation from this line. Lens optical density was also
      assessed by comparing absolute scotopic thresholds to the extinction spectrum of
      rhodopsin. Scotopic thresholds and lens density values of the two groups were
      evaluated using independent samples t-tests. The scotopic thresholds, and
      associated noise, did not differ between the schizophrenia and control
      participants. Lens density was also nearly identical between groups. These
      results suggest that magnocellular deficits in schizophrenia may not be due to
      problems at the level of the rods but are more likely to occur later in the
      visual pathway.

PMID- 16626943
TI  - A validation of a new measure of activity in psychosis.
AB  - Despite demonstrated relationships between activity and clinical change, we lack
      effective measures of time use in psychosis. Existing time budget measures of
      activity are demanding to complete, and thus unsuited to routine clinical use as
      measures of change. Less burdensome 'check-box' measures are prone to bias and
      omission in the activities selected. We recently devised a simplified time budget
      measure of activity in psychosis which was piloted on a small sample [Jolly, S.,
      Garety, P., Dunn, G., White, J., Aitken, M., Challocombe, F., Griggs, M.,
      Wallace, M., Craig, T. 2005. A pilot validation study of a new measure of
      activity in psychosis. Soc. Psychiatry Psychiatr. Epidemiol. 40, 905-911]. This
      study is a larger scale validation. 276 participants with a recent relapse of non
      affective psychosis completed the new time budget, together with an established
      measure of global social functioning, measures of positive and negative psychotic
      symptoms, positive symptom distress and affect. The time budget measure showed a
      correlation of 0.5 with both the SOFAS and the SANS avolition/apathy subscale.
      Activity levels were related to psychotic symptomatology, both positive and
      negative. Positive symptom distress was more strongly associated with activity
      levels than symptom severity and affective disturbance. We conclude that the time
      budget measure can be used as an indicator of social functioning, with potential
      as a measure of therapeutic change. We are currently investigating its
      sensitivity in this context.

PMID- 16626944
TI  - Resting hypofrontality in schizophrenia: A study using near-infrared time
      resolved spectroscopy.
AB  - Hypofrontality has been a major finding obtained from functional neuroimaging
      studies on schizophrenia, although there have also been contradictory results
      that have questioned the reality of hypofrontality. In our previous study, we
      confirmed the existence of activation hypofrontality by using a 2-channel
      continuous-wave-type (CW-type) near-infrared spectroscopy (NIRS) instrument. In
      this study, we employed a single-channel time-resolved spectroscopy (TRS)
      instrument, which can quantify hemoglobin (Hb) concentrations based on the photon
      diffusion theory, to investigate resting hypofrontality. A pair of incident and
      detecting light guides was placed on either side of the forehead at approximately
      Fp2-F8 or Fp1-F7 alternately in 14 male schizophrenic patients and 16 age-matched
      male control subjects to measure Hb concentrations at rest. The patients were
      also measured with a 2-channel CW-type NIRS instrument during the performance of
      a random number generation (RNG) task. A reduced total hemoglobin concentration
      (t-Hb) less than 60 microM (the mean value of the control subjects-1.5 SD) was
      observed bilaterally in 4 patients and only in the left side in 3 patients.
      Activation hypofrontality was more manifest in these patients than in the
      remaining 7 patients despite the same task performance. This decreased t-Hb was
      related to the duration of illness, and it was not observed in patients whose
      duration of illness was less than 10 years. These results indicate that resting
      hypofrontality is a chronically developed feature of schizophrenia. This does not
      necessarily represent frontal dysfunction, but may reflect anatomical and/or
      functional changes in frontal microcirculation.

PMID- 16626945
TI  - Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other
      psychotic disorders.
AB  - Cognitive deficits have been found to be prevalent in early onset schizophrenia.
      Whether these deficits also characterise other early onset psychotic disorders to
      a similar degree is unclear, as very few comparative studies have been done. The
      primary purpose of this study was to compare the profile and severity of
      cognitive impairments in first-episode early onset psychotic patients who
      received the schizophrenia diagnosis to those diagnosed with other non-organic,
      non-affective psychotic disorders. The secondary purpose was to examine whether
      the profile of cognitive deficits, in terms of intelligence, executive functions,
      memory, attention and processing speed was global or specific. First-episode
      psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18
      of whom were diagnosed with schizophrenia, and 21 with other non-organic, non
      affective psychoses, using ICD-10 criteria. A healthy control group (N = 40) was
      included, matched on gender and age. Cognitive functions were assessed using WISC
      III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschke's
      selective reminding task. A similar profile and level of impairment was found on
      measures of attention, executive functions, reaction time, and memory in the
      schizophrenic and psychotic adolescent groups. However, analyses of WISC-III
      factor profiles suggested that early onset schizophrenia patients may have more
      global IQ deficits than non-organic, non-affective psychoses when examined
      recently after illness onset. Compared to the deficits of adult schizophrenia
      described in the literature, the results suggest relatively spared simple
      reaction times in early onset patients.

PMID- 16626946
TI  - Social isolation stress and neuroactive steroids.
AB  - Social isolation of rats immediately after weaning is associated to a reduction
      in the cerebrocortical and plasma concentrations of progesterone and its
      metabolites 3alpha,5alpha-TH PROG and 3alpha,5alpha-THDOC. Although we found that
      the basal plasma concentration of adrenocorticotropic hormone in isolated rats
      was slightly decreased compared with that in group-housed animals no other
      significant changes were found in the steroidogenic machinery (peripheral
      benzodiazepine receptors, steroidogenic regulatory protein (StAR)). However, the
      functional response of the hypothalamic-pituitary-adrenal axis HPA axis to an
      acute stressful stimulus (foot shock), or to an acute injection of ethanol or
      isoniazid is markedly increased in isolated rats. Behavioral studies have also
      indicated that the ability of ethanol to inhibit isoniazid-induced convulsions is
      greater in isolated rats than in group-housed animals and this effect of
      isolation is prevented by treatment with the 5alpha-reductase inhibitor
      finasteride. Social isolation modified the effects of ethanol on the amounts of
      StAR mRNA and protein in the brain suggesting an alteration in the mechanism of
      cholesterol transport in mitochondria. Moreover, the amounts of the alpha4 and
      delta subunits of the GABA(A) receptor in the hippocampus were increased in
      isolated rats, and these effects were accompanied by an increase in GABA(A)
      receptor-mediated tonic inhibitory currents in granule cells of the dentate
      gyrus. Ethanol also increased the amplitude of GABA(A) receptor-mediated
      miniature inhibitory postsynaptic currents (mIPSC) recorded from CA1 pyramidal
      neurons with a greater potency in hippocampal slices prepared from socially
      isolated rats than in those from group-housed, an effect inhibited by
      finasteride.

PMID- 16626947
TI  - Visualization of the cortical dopamine transporter in type 1 and 2 alcoholics
      with human whole hemisphere autoradiography.
AB  - We measured cortical dopamine transporter (DAT) in Cloninger type 1 and 2
      alcoholics by using [(125)I]PE2I as a radioligand in human postmortem whole
      hemispheric autoradiography, and evaluated the putative correlations of DAT
      between cortical areas and nucleus accumbens. There was a low, but distinct
      cortical binding in the cryosections. The mean binding was generally higher in
      both groups of alcoholics compared to controls, and the results reached
      statistical significance with a large effect size (1.25) in the temporal cortex
      of type 2 alcoholics. This is surprising, because several studies have reported
      lower DAT densities in the striatum among alcoholics compared to controls.
      Moreover, the density of DAT had a statistically significant positive correlation
      between temporal cortex and nucleus accumbens in controls, whereas among type 2
      alcoholics the correlation was statistically significantly negative, which may
      suggest some pathology relating to the antisocial behaviour of these alcoholics.

PMID- 16626948
TI  - Cationic liposomes modified with non-ionic surfactants as effective non-viral
      carrier for gene transfer.
AB  - A defined change in formulation components affects the physical and chemical
      characteristics of cationic liposomes (CLs) carriers in many ways. Therefore, a
      great degree of control can be exercised over the structure by modifying the CLs
      with various materials, leading to new innovations for carrier improvement. In
      the present study, surface modifications of cationic liposomes with non-ionic
      surfactants--sorbitan monoesters serials (Span 85, 80, 40 and 20) were carried
      out for developing a new gene transfer carrier. Span modified cationic liposomes
      (Sp-CLs) were prepared by reverse phase evaporation method (RPV) and self
      assemble complexes of antisense oligonucleotides/surfactant modifying cationic
      liposomes were prepared by auto-coacervation through electrostatic effect.
      Characterization of Sp-CLs and the self-assembled complex was performed by
      electron microscope, particle size, zeta potential, turbidity and agarose
      electrophoresis. Furthermore, in vitro cellular uptake experiment showed that
      Span plays a role in enhancing the cellular uptake of encapsulated
      oligonucleotides mediated by Sp-CLs by the endocytosis-dependent route. CLs
      modified with Span 40 significantly facilitated the cellular uptake by COS-7
      cells and HeLa cells; also showed some positive effect on gene expression. That
      suggests it is a potential non-viral carrier for efficient gene transfer.

PMID- 16626949
TI  - Mexican American elders have similar severities of COPD despite less tobacco
      exposure than European American elders.
AB  - INTRODUCTION: Hispanics are the fastest growing ethnicity of the US population
      and the largest subset includes those of Mexican origin. Hispanics, including
      Mexican Americans (MAs), consistently report less tobacco exposure than European
      Americans (EAs), but limited data are available regarding differences in the
      clinical characteristics, severity of airflow obstruction, and functional status
      between MAs and EAs with chronic obstructive pulmonary disease (COPD). METHODS:
      Participants in a community-based study of aging and frailty among MAs and EAs,
      San Antonio Longitudinal Study of Aging, underwent spirometry. Participants with
      spirometry values consistent with COPD by Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) criteria are described here. RESULTS: Thirty-four
      percent (248/721) of the participants who underwent spirometry had evidence of
      GOLD Stages 1-4 COPD. Significantly more MAs with COPD reported being never
      smokers compared to EAs with COPD. Among those with COPD who also smoked, MAs
      reported significantly less tobacco exposure than EAs (15.7 vs. 32.4 pack-years,
      respectively), but both groups had surprisingly similar severities of airflow
      obstruction. Additionally, MAs had worse functional status and perceived health
      than did EAs. CONCLUSIONS: Despite significantly less exposure to tobacco smoke,
      MAs with COPD had a similar degree of obstruction to airflow compared with EAs
      with COPD. Healthcare providers should have a high index of suspicion for COPD in
      MAs who are exposed to even small amounts of cigarette smoke.

PMID- 16626950
TI  - Chronic respiratory symptoms, spirometry and knowledge of COPD among general
      population.
AB  - RATIONALE: Infradiagnosis of chronic obstructive pulmonary disease (COPD) may be
      related to the lack of knowledge about the disease and/or the scarce use of
      diagnostic procedures. This study analyses the frequency of respiratory symptoms
      and the knowledge about COPD in the general population, together with the use of
      spirometry in individuals at risk of COPD. POPULATION AND METHOD: A telephone
      survey was carried out in 6758 subjects older than 40 years, stratified by age,
      habitat (urban or rural) and region, screened by random-digit dialling. RESULTS:
      Up to 24% reported having at least one chronic respiratory symptom and 20.9% had
      a self-reported respiratory diagnosis. A total of 19.2% were active smokers and
      40% had never tried to quit. Only 60% of the individuals with chronic symptoms
      had consulted a physician and, of them, only 45% had undergone spirometry.
      Spirometry was mentioned more frequently by subjects attended by pulmonologists
      than by GPs (67.6 vs. 28.6%; P<0.001). The term COPD was identified only by 8.6%
      of the participants. CONCLUSIONS: Many individuals with respiratory symptoms do
      not request medical attention and do not attempt to quit smoking. There is a lack
      of knowledge about COPD. Physicians should more actively inform about the disease
      and increase the use of spirometry for early detection.

PMID- 16626951
TI  - Respiratory muscle training in persons with spinal cord injury: a systematic
      review.
AB  - The purpose of this paper was to review the effectiveness of respiratory muscle
      training (RMT) on respiratory muscle strength and endurance, pulmonary function,
      quality of life, respiratory complications and exercise performance in persons
      with spinal cord injury. A MEDLINE (National Library of Medicine, Bethesda, MD,
      USA) database was used for selection of the literature (from 1980 to November
      2004), and relevant references from peer-reviewed articles were retrieved as
      well. Studies investigating the effects of RMT (i.e. resistive breathing weight
      lifting or normocapnic hyperpnea) in persons with spinal cord injury were
      selected. Two independent reviewers investigated controlled studies for
      methodological quality by using a modification of the framework for
      methodological quality. Methodological quality ranged between 15 and 29 (maximal
      feasible score=40). Twenty-three papers were retrieved and six controlled trials
      were kept for further analysis. A meta-analysis and calculation of effect-size of
      each individual study and weighted summary effect-size was intended. However,
      unreported data and heterogeneity in outcome variables did not allow performing a
      meta-analysis. From the systematic review it is concluded that RMT tended to
      improve expiratory muscle strength, vital capacity and residual volume.
      Insufficient data was available to make conclusions concerning the effects on
      inspiratory muscle strength, respiratory muscle endurance, quality of life,
      exercise performance and respiratory complications.

PMID- 16626952
TI  - Exophiala dermatitidis infection in non-cystic fibrosis bronchiectasis.
AB  - A 54-year-old female presented with an exacerbation of right middle lobe
      bronchiectasis. A bronchoscopic bronchial washing and repeated trials of sputum
      culture consistently recovered no other infectious agent except Exophiala
      dermatitidis. Her illness was improved by administrations of intravenous
      miconazole and nebulized amphotericin B when sputum cultures yielded no fungi,
      demonstrating a pathogenic role of the fungi. The present case illustrates E.
      dermatitidis as a pathogenic agent in non-cystic fibrosis bronchiectasis.

PMID- 16626953
TI  - Bayesian analysis using continuous likelihood ratios for identifying pleural
      exudates.
AB  - STUDY OBJECTIVES: To ascertain if equations that calculate continuous likelihood
      ratios (CLRs) for pleural exudates improve pleural fluid categorization,
      especially when false positive or false negative test results are obtained by
      using Light's criteria. DESIGN AND SETTING: Retrospective review of the clinical
      and pleural fluid data from a consecutive series of patients with pleural
      effusion who underwent thoracentesis at the University Hospital Arnau de Vilanova
      (Lleida, Spain) over an 11-year period. PATIENTS AND METHODS: A total of 1490
      patients with pleural effusion (298 transudates and 1192 exudates) were recruited
      into the study. The presence of a transudate or exudate was established by
      clinical judgment. We examined the comparative diagnostic accuracy of 4 tests
      (i.e. pleural fluid protein and lactate dehydrogenase (LDH), and pleural fluid to
      serum protein and LDH ratios) for discriminating between transudates and
      exudates. Decision thresholds were determined by receiver operating
      characteristics (ROC) analysis. Equations for calculating CLRs derived from a
      logistic regression analysis based on a previously described method. RESULTS:
      Individual pleural fluid tests did not differ in their diagnostic accuracies
      according to ROC analysis. We calculated CLRs for the elements of Light's
      criteria and pleural fluid protein, and also illustrated the sequential use of
      CLRs for determining posttest probabilities. Overall, CLR formulas had marginal
      performance for the correct categorization of pleural fluid. CONCLUSIONS: CLRs
      provide a probabilistic statement as to the likelihood an effusion is a
      transudate or exudate. However, clinical judgment is little changed by the
      application of CLRs, and in doubtful cases a great amount of uncertainty remains.
      This Bayesian approach is likely to have no major impact on the clinical
      practice.

PMID- 16626954
TI  - Plant-based formulation in COPD.

PMID- 16626955
TI  - Efficacy and safety of montelukast in adults with asthma and allergic rhinitis.
AB  - Several clinical studies have confirmed the effectiveness of montelukast 10mg
      orally in adults with both asthma and allergic rhinitis. The objective of this
      phase IV study was to investigate the efficacy and safety of montelukast 10mg in
      adults with both asthma and allergic rhinitis in a real-life setting. Data from
      5855 patients (mean age: 42.8+/-15.4 years) were collected and analyzed following
      treatment for 4-6 weeks. Efficacy was analyzed by comparing baseline values of:
      general, day- and night-time improvement in asthma symptoms, need for rescue
      medication or inhaled corticosteroids (ICSs), general and specific improvement in
      allergic rhinitis symptoms, reduction in rhinitis medication use, and general and
      specific quality of life (QoL) improvement with values collected at the end of
      the observation period of 4-6 weeks. Following treatment with 10mg montelukast
      86.5% (n=4547) of patients reported a strong or marked improvement in day-time
      asthma symptoms and 88.5% (n=4367) reported improvement in night-time symptoms. A
      similarly high proportion of patients had a strong or marked improvement in all
      symptoms of allergic rhinitis (i.e. sneezing/itching (84%), rhinorrhea (81.7%),
      nasal congestion (79.3%), watery eyes (78.4%) and red or burning eyes (77.7%).
      The use of asthma and rhinitis medication was also reduced. 92.3% (n=5685) of all
      patients intended to continue montelukast therapy. Overall QoL was "very good" or
      "good" in 85.2% of patients (n=4991) and a "strong" or "marked" improvement in
      each of the four domains of sleep, work, everyday life and physical activity.
      Montelukast was well tolerated. Adverse drug reactions occurred in 14 out of 6158
      patients. None of the adverse events was serious. Accordingly, montelukast 10mg
      is a safe and effective treatment for patients with both asthma and allergic
      rhinitis.

PMID- 16626956
TI  - Effect of formoterol, tiotropium, and their combination in patients with acute
      exacerbation of chronic obstructive pulmonary disease: a pilot study.
AB  - The aim of our study was to evaluate the pharmacodynamic effects of 1-day
      treatment with formoterol, tiotropium and their combination in patients with
      acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Twenty-one
      (19 males, mean age 72+/-8 years, mean FEV1 38+/-14% of predicted values)
      patients with mild to moderate AECOPD were enrolled. Patients received formoterol
      (12 microg deliver via Modulite b.i.d.), tiotropium (18 microg dry powder
      capsules delivered via HandiHaler once daily), and their combination, in
      randomized sequence. Serial measurements of FEV1, FVC, IC, SpO2 and HR were
      performed over 24h. Formoterol, tiotropium, and their combination significantly
      improved the area under curves (AUCs) for FEV1, FVC and IC over 12 and 24h. The
      mean FEV1, FVC and IC AUC(0-12h) and AUC(0-24h) after formoterol and tiotropium
      combination were significantly higher than formoterol and tiotropium alone,
      whereas the differences between the two single drugs were not statistically
      significant. Formoterol, either alone or in combination with tiotropium, elicited
      a significantly faster onset of action, and combination elicited a greater
      maximum bronchodilation than both single drugs in terms of FEV1 and FVC. After
      24h the bronchodilating effect of the three treatments disappeared, with the
      exception of the combination on FEV1. The results of this study have documented
      that, although the time course of the effects of evaluated drugs differs
      significantly from that in stable COPD, with a shorter bronchodilation both for
      tiotropium and formoterol, these two long-acting bronchodilators appear to also
      be complementary in mild to moderate AECOPD.

PMID- 16626958
TI  - Cytotoxicity of abietane diterpenoids from Perovskia abrotanoides and of their
      semisynthetic analogues.
AB  - Seven known abietane diterpenoids and 11-O- and 12-O-acetylcarnosic acids were
      isolated from a methanol extract of Perovskia abrotanoides (Labiatae). Structure
      and cytotoxic activity relationships (SAR) of the natural and semisynthetic
      analogues of the presently isolated abietane diterpenoids were studied by using
      P388 murine leukemia cells.

PMID- 16626957
TI  - Soy protein with and without isoflavones fails to substantially increase
      postprandial antioxidant capacity.
AB  - Five methods for the assessment of antioxidant capacity [whole plasma conjugated
      diene formation, low-density lipoprotein oxidation susceptibility, ferric
      reducing ability of plasma, oxygen radical absorbance capacity and perchloric
      acid-treated oxygen radical absorbance capacity (PCA-ORAC)] were used in a
      randomized, double blind, crossover study to determine the acute postprandial
      antioxidant protection imparted by the isoflavone component of soy. On separate
      days, 16 subjects consumed one of three isocaloric shakes containing 25 g of
      protein in the form of soy, with 107 mg of total aglycone units of isoflavones,
      soy with trace isoflavones (<4 mg) or total milk protein. Blood was collected at
      baseline, 4 h, 6 h and 8 h after consumption. Antioxidant capacity, serum
      isoflavone levels, fat-soluble antioxidants and plasma vitamin C levels were
      evaluated. Repeated measures analysis of variance showed no significant
      differences (P=.05) within treatments over time in four of five antioxidant
      capacity measurements. Significant differences over time between the soy with
      trace isoflavones and the total milk protein group were observed using the PCA
      ORAC assay. It can be concluded that, on an acute basis, a significant increase
      in serum antioxidant capacity is not detectable following consumption of soy
      protein.

PMID- 16626959
TI  - Some remarks on the indoor radon distribution in a country.
AB  - From the point of view of indoor radon activity concentrations, a country is
      characterized correctly by two parameters (GM and GSD) of a lognormal
      distribution if and only if hypothesis tests do not reject the distribution of
      the local radon activity concentrations as a lognormal one. The authors introduce
      a way to obtain an empirical distribution using a stratum system covering almost
      the whole country and in each stratum the lognormal model is acceptable according
      to hypothesis tests. The sample for the analysis is provided by the measurement
      of radon level in 15,619 Hungarian homes.

PMID- 16626960
TI  - Identification of gene expression changes in transgenic C. elegans overexpressing
      human alpha-synuclein.
AB  - Alpha-synuclein containing cellular inclusions are a hallmark of Parkinson
      Disease, Lewy Body Dementia, and Multiple System Atrophy. A genome wide
      expression screen was performed in C. elegans overexpressing both wild-type and
      A53T human alpha-synuclein. 433 genes were up- and 67 genes down-regulated by
      statistical and fold change (> or <2) criteria. Gene ontology (GO) categories
      within the regulated gene lists indicated over-representation of development and
      reproduction, mitochondria, catalytic activity, and histone groups. Seven genes
      (pdr-1, ubc-7, pas-5, pas-7, pbs-4, RPT2, PSMD9) with function in the ubiquitin
      proteasome system and 35 mitochondrial function genes were up-regulated. Nine
      genes that form histones H1, H2B, and H4 were down-regulated. These results
      demonstrate the effects of alpha-synuclein on proteasome and mitochondrial
      complex gene expression and provide further support for the role of these
      complexes in mediating neurotoxicity. The results also indicate an effect on
      nuclear protein genes that suggests a potential new avenue for investigation.

PMID- 16626961
TI  - Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating
      a cPLA2-dependent sphingomyelinase-ceramide pathway.
AB  - Recent data have revealed that soluble oligomeric amyloid-beta peptide (Abeta)
      may be the proximate effectors of neuronal injuries and death in Alzheimer's
      disease (AD) by unknown mechanisms. Consistently, we recently demonstrated the
      critical role of a redox-sensitive cytosolic calcium-dependent phospholipase A2
      (cPLA2)-arachidonic acid (AA) pathway in Abeta oligomer-induced cell death.
      According to the involvement of oxidative stress and polyunsaturated fatty acids
      like AA in the regulation of sphingomyelinase (SMase) activity, the present study
      underlines the role of SMases in soluble Abeta-induced apoptosis. Soluble Abeta
      oligomers induced the activation of both neutral and acidic SMases, as
      demonstrated by the direct measurement of their enzymatic activities, by the
      inhibitory effects of both specific neutral and acidic SMase inhibitors, and by
      gene knockdown using antisense oligonucleotides. Furthermore, soluble Abeta
      mediated activation of SMases and subsequent cell death were found to be
      inhibited by antioxidant molecules and a cPLA2-specific inhibitor or antisense
      oligonucleotide. We also demonstrate that sphingosine-1-phosphate is a potent
      neuroprotective factor against soluble Abeta oligomer-induced cell death and
      apoptosis by inhibiting soluble Abeta-induced activation of acidic
      sphingomyelinase. These results suggest that Abeta oligomers induce neuronal
      death by activating neutral and acidic SMases in a redox-sensitive cPLA2-AA
      pathway.

PMID- 16626962
TI  - Inhibitory effects of pesticides on proteasome activity: implication in
      Parkinson's disease.
AB  - Epidemiological studies have suggested a correlation of pesticides and
      Parkinson's disease (PD) while genetic and biochemical studies have implicated
      the ubiquitin-proteasome system (UPS) in the pathogenesis of PD. In the present
      studies, we tested the hypothesis that pesticide exposure increases the risk of
      developing PD by inhibiting the UPS. The effects of pesticides on proteasome
      activity were examined in SK-N-MC neuroblastoma cells overexpressing a GFP
      conjugated proteasome degradation signal, GFP(u). Six out of 25 representative
      pesticides, including rotenone, ziram, diethyldithiocarbamate, endosulfan,
      benomyl, and dieldrin, showed inhibitory effects on proteasome activities at low
      concentrations (10 nM to 10 microM). Unlike proteasome inhibitors, they did not
      inhibit 20 S proteasome activities in cell lysates. Except for rotenone, the
      other five pesticides did not induce significantly cellular oxidative stress. The
      cytotoxic effects of these pesticides were closely correlated with proteasome
      inhibition. Our results suggest proteasome inhibition as a potential mechanism
      for the epidemiological association of pesticides and PD.

PMID- 16626963
TI  - MAPCAs, bronchials, monkeys, and men.

PMID- 16626964
TI  - Outcomes in patients with interrupted aortic arch and associated anomalies: a 20
      year experience.
AB  - OBJECTIVE: The surgical results for the repair of interrupted aortic arch (IAA)
      have evolved in recent years. We report our results for staged repair of this
      complex congenital malformation. METHODS: Sixty-five patients (mean age, 16.9+/
      41.7 days) were diagnosed with IAA and referred for surgical therapy. The
      surgical management strategy at our institution between 1982 and 2005 has been
      one-stage complete repair (n=13) or staged repair (n=52) in selected patients.
      Non-complex patients (group I, n=51) had a ventricular septal defect (87%),
      aortopulmonary window (8%), and left ventricular outflow tract obstruction (27%).
      Group II (n=14) were patients with Taussig-Bing double outlet right ventricle
      (n=6) or truncus arteriosus (n=8). Method of staged repair of IAA was to transect
      and turn down the left carotid artery and anastomosis it to the descending aorta
      (n=41) or graft interposition (n=2) combined with a pulmonary artery (PA) banding
      followed in a few months by delayed ventricular septal defect (VSD) closure and
      PA de-banding. RESULTS: There were 5 early and 10 late deaths. The actuarial
      survival including early mortality was 92% at 1 year, 81% at 5 years, and 76% at
      10 and 15 years. There was an 81% 15-year survival for children in group I
      compared with a 54% for children in group II (p<0.001). Risk factors for
      increased mortality by univariate analysis were as follows: (1) primary aortic
      anastomosis (p=0.03), (2) presence of complex anomalies (p=0.05), and (3) initial
      IAA repair performed before 1994 (p=0.05). Actuarial freedom from any type of
      aortic reoperation or intervention was 86% at 1 year, 69% at 5 years, and 60% at
      10 and 15 years. Univariate and multivariate analyses identified no tested
      variables as risk factors for reoperation. The majority (86%) was in New York
      Heart Association (NYHA) class I, and 14% remained in NYHA class II. During the
      postoperative course there were no neurologic deficits, seizures, and growth
      disturbances in any patient. CONCLUSION: Staged repair of IAA using a left
      carotid artery turn down can be safely applied in IAA patients with and without
      other intracardiac anomalies with good results. Use of the left carotid artery
      for arch reconstruction did not result in any detectable neurological events or
      growth disturbances later in life. Associated anomalies played an important role
      in outcomes. The long-term probability for reoperation and/or reintervention
      remains high regardless of operative technique.

PMID- 16626965
TI  - Effects of purified poloxamer 407 gel on vascular occlusion and the coronary
      endothelium.
AB  - OBJECTIVE: Vascular occlusion during off-pump coronary surgery often results in
      sub-optimal visualization and endothelial damage of the target vessel. We have
      previously reported the safety of purified poloxamer 407, a gel with reverse
      thermosensitive properties, in a model of off-pump coronary occlusion. The aim of
      this study was to evaluate different gel concentrations and their effects on
      coronary occlusion time, myocardial contractility, endothelial function, and
      markers of myocardial injury and apoptosis. METHODS: Yorkshire swine (30-35 kg)
      underwent sternotomy and mid-LAD occlusion using either microvascular clamps
      (n=6) or varying quantities of three different concentrations (20%; n=6, 22.5%;
      n=3, and 25%; n=3) of purified poloxamer 407 gel. Distal LAD flow, left
      ventricular pressure, and in vitro microvascular reactivity were assessed.
      Molecular markers of myocardial injury and apoptosis were assessed using Western
      blotting. RESULTS: Duration of ischemia correlated significantly with the amount
      of injected gel for the 20% and 22.5% formulations (Spearman r=0.64, p=0.02 and
      r=0.85, p=0.03, respectively) but not for the 25% gel (r=0.22, p=0.66). There
      were no significant differences in LV contractility (maximum+dp/dt) (p=0.86) as
      well as LAD flow (p=0.25) during reperfusion in the four groups. Microvessel
      relaxation to adenosine diphosphate in the ischemic territory was impaired with
      higher concentrations of the gel, 22.5% (-14.8+/-7.5% vs control at 10(-5)mol/L,
      p<0.05) and 25% gel (-24.0+/-7.6% vs control at 10(-5)mol/L, p<0.001) but not
      with the 20% gel. Endothelium-independent relaxation to sodium nitroprusside was
      preserved in all groups. Cleaved poly(ADP-ribose) polymerase, a marker of
      myocardial injury and apoptosis, was elevated in the ischemic myocardium in all
      groups (p=0.02 vs non-ischemic myocardium) with no significant differences
      between the groups (p=0.70). Phosphorylation of Bad, an anti-apoptotic protein,
      was significantly reduced in the ischemic territory (p=0.04). No changes were
      observed in other markers of myocardial apoptosis. CONCLUSIONS: Purified
      poloxamer 407 gel is effective for temporary coronary vascular occlusion.
      Coronary artery occlusion time is related to gel concentration and the quantity
      of gel injected. The higher gel concentrations may cause endothelial dysfunction
      of the distal vasculature and therefore should be avoided.

PMID- 16626966
TI  - Video-assisted right supradiaphragmatic thoracic duct ligation for non-traumatic
      recurrent chylothorax.
AB  - BACKGROUND: Chylothorax is an uncommon disorder with respiratory, nutritional and
      immunological manifestations. Surgical management is indicated in case of
      recurrence or failure after conservative treatment. We report our experience with
      video-assisted right-sided supradiaphragmatic thoracic duct ligation for non
      traumatic, non-postoperative persistent or recurrent chylothorax. PATIENTS AND
      METHODS: The medical records of six patients operated at our institution between
      1999 and 2004 were retrospectively reviewed. A right-sided chylothorax was found
      in four patients, a left-sided in one, and a bilateral in one. Three patients
      developed chylothorax after chemotherapy and chest irradiation for malignant
      diseases (lymphoma in two patients and breast cancer in one), one in the context
      of lymphangioleiomyomatosis, one due to a non-diagnosed lymphoma, and one after
      heart transplantation. RESULTS: The mean operative time was 102 min, with an
      average length of hospital stay of 14 days. Persistent cessation of chylous
      effusion within 7 days after surgery was observed in 5/6 patients without
      recurrence during a mean follow-up time of 41 months. One patient with
      undiagnosed mediastinal lymphoma required re-operation and thoracic duct ligation
      on day 8 by right-sided thoracotomy due to persistent chylothorax. No 30-day
      mortality was recorded. Two patients presented postoperative complications
      including respiratory insufficiency requiring mechanical ventilation in one, and
      chylous ascites development requiring peritoneo-venous LeVeen shunting in one
      patient. CONCLUSIONS: Recurrent or persistent non-traumatic chylothorax may be
      successfully treated by video-assisted right supradiaphragmatic thoracic duct
      ligation.

PMID- 16626967
TI  - The evidence on the effectiveness of management for malignant pleural effusion: a
      systematic review.
AB  - The aim of this study was to review systematically the available evidence on
      pleurodesis for malignant effusion, focusing on the choice of the agents, route
      of delivery and other strategies to improve outcomes. Four electronic databases
      (MEDLINE, EMBASE, Web of Science and Cochrane Controlled Trials Register) were
      searched, reference lists checked and letters requesting details of unpublished
      trials and data sent to authors of previous trials. Studies of malignant pleural
      effusion in humans were selected with no language restrictions applied. Criteria
      for randomised clinical trial (RCT) eligibility were random allocation of
      patients and non-concurrent use of another experimental medication or device.
      Methodological quality evaluation of the trials was based on randomisation,
      blinding, allocation concealment and intention to treat analysis. A random effect
      model was used to combine the relative risk estimates of the treatment effects
      whenever pooling for an overall effect was considered appropriate. Forty-six RCTs
      with a total of 2053 patients with malignant pleural effusions were reviewed for
      effectiveness of pleurodesis. Talc tended to be associated with fewer recurrences
      when compared to bleomycin (RR, 0.64; 95% CI, 0.34-1.20) and, with more
      uncertainty, to tetracycline (RR, 0.50; 95% CI, 0.06-4.42). Tetracycline (or
      doxycycline) was not superior to bleomycin (RR, 0.92; 95% CI, 0.61-1.38). When
      compared with bedside talc slurry, thoracoscopic talc insufflation was associated
      with a reduction in recurrence (RR, 0.21; 95% CI, 0.05-0.93). Strategies such as
      rolling the patient after instillation of the sclerosing agent, protracted
      drainage of the effusion and use of larger chest tubes were not found to have any
      substantial advantages. Talc appears to be effective and should be the agent of
      choice for pleurodesis. Thoracoscopic talc insufflation is associated with fewer
      recurrences of effusions compared with bedside talc slurry, but this is based on
      two small studies. Where thoracoscopy is unavailable bedside talc pleurodesis has
      a high success rate and is the next best option.

PMID- 16626970
TI  - Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the
      lesioned spinal cord.
AB  - We have characterized in the contusion-lesioned murine spinal cord the behavior
      of acutely implanted epidermal neural crest stem cells (EPI-NCSC, formerly
      eNCSC). EPI-NCSC, a novel type of multipotent adult stem cell, are remnants of
      the embryonic neural crest. They reside in the bulge of hair follicles and have
      the ability to differentiate into all major neural crest derivatives (Sieber
      Blum, M., Grim, M., Hu, Y.F., Szeder, V., 2004. Pluripotent neural crest stem
      cells in the adult hair follicle. Dev. Dyn. 231, 258-269). Grafted EPI-NCSC
      survived, integrated, and intermingled with host neurites in the lesioned spinal
      cord. EPI-NCSC were non-migratory. They did not proliferate and did not form
      tumors. Significant subsets expressed neuron-specific beta-III tubulin, the
      GABAergic marker glutamate decarboxylase 67 (GAD67), the oligodendrocyte marker,
      RIP, or myelin basic protein (MBP). Close physical association of non-neuronal
      EPI-NCSC with host neurites was observed. Glial fibrillary acidic protein (GFAP)
      immunofluorescence was not detected. Collectively, our data indicate that
      intraspinal EPI-NCSC demonstrate several desirable characteristics that may
      include local neural replacement and re-myelination.

PMID- 16626971
TI  - Self-reported injury and physical activity levels: United States 2000 to 2002.
AB  - PURPOSE: The aim of the study is to compare national estimates of the incidence
      of self-reported all-cause and activity-specific injuries in adults with
      differing leisure-time physical activity levels. METHODS: Data were analyzed from
      the 2000 to 2002 National Health Interview Survey. Leisure-time physical activity
      levels were categorized as active, insufficiently active, and inactive. RESULTS:
      Age-adjusted incidences of all-cause injury did not differ by leisure-time
      physical activity level (active, 89.3/1000; 95% confidence interval [CI], 81.8
      96.8; insufficiently active, 81.6/1000; 95% CI, 73.1-90.1; and inactive,
      86.3/1000; 95% CI, 78.6-93.9). Active respondents (29.4/1000; 95% CI, 25.2-33.6)
      had a greater incidence of injury related to sport and leisure-time activities
      than inactive respondents (15.2/1000; 95% CI, 12.1-18.3), whereas inactive
      respondents (71.1/1000; 95% CI, 63.9-78.2) had a greater incidence of injury
      related to nonsport and non-leisure-time activities than active respondents
      (59.9/1000; 95% CI, 53.6-66.2). Results were unchanged after multivariate control
      for confounding factors. CONCLUSIONS: Although the incidence of sport and leisure
      time injuries is associated with participation in leisure-time physical activity,
      no association was observed between leisure-time physical activity and overall
      injuries.

PMID- 16626972
TI  - Increased brain activation during verbal learning in obstructive sleep apnea.
AB  - This study examined the cerebral response to a verbal learning (VL) task in
      obstructive sleep apnea (OSA) patients. Twelve OSA patients and 12 controls were
      studied with functional magnetic resonance imaging (FMRI). As hypothesized, VL
      performance was similar for both groups, but OSA patients showed increased brain
      activation in several brain regions. These regions included bilateral inferior
      frontal and middle frontal gyri, cingulate gyrus, areas at the junction of the
      inferior parietal and superior temporal lobes, thalamus, and cerebellum. Better
      free recall performance in the OSA group was related to increased cerebral
      responses within the left inferior frontal gyrus and left supramarginal area.
      Recall was negatively related to activation within the left inferior parietal
      lobe. The findings support the predictions that intact performance in OSA
      patients is associated with increased cerebral response. Recruitment of
      additional brain regions to participate in VL performance in OSA patients likely
      represents an adaptive compensatory recruitment response, similar to that
      observed in young adults following total sleep deprivation and in healthy older
      adults. These data, and those of the only other FMRI study in OSA, suggest that
      individuals with OSA show characteristic differences in the BOLD signal response
      to cognitive challenges. Including subjects with untreated OSA in neuroimaging
      studies may potentially influence the results by altering individual and group
      level activation patterns. Given this, future neuroimaging studies may want to be
      aware of this potential confound.

PMID- 16626973
TI  - Modulatory role of cyclooxygenase-2 in cerebrovascular coupling.
AB  - To investigate the role of cyclooxygenase-2 (COX-2) in the cerebrovascular
      coupling, hemodynamic and neuronal responses to forepaw stimulation were measured
      in alpha-chloralose-anesthetized rats (N = 18) before and after intravenous
      administration of Meloxicam (MEL), a preferential COX-2 inhibitor, and following
      a bolus of prostaglandin E(2) (PGE(2)), a prominent vasodilatatory product of COX
      2 catalyzed metabolism of arachidonic acid. The cerebral blood flow (CBF) and
      blood-oxygenation-level-dependent (BOLD) response was quantified using continuous
      arterial spin labeling magnetic resonance imaging. Neuronal activity was measured
      by recording somatosensory-evoked potentials (SEPs) via intracranial electrodes.
      Both MEL and PGE(2) had a significant effect on the activation-elicited CBF (P <
      10(-6)) and BOLD (P < 10(-6)) responses, without affecting the baseline
      perfusion. Meloxicam decreased brain COX enzymatic activity by 57 +/- 14% and
      decreased the stimulation-induced CBF response to 32 +/- 2% and BOLD to 46 +/- 1%
      of their respective pre-drug amplitudes. In turn, PGE(2) bolus resulted in a
      partial recovery of functional hyperemia, with the CBF response recovering to 52
      +/- 3% and the BOLD response to 56 +/- 2% of their values prior to MEL
      administration. There was no concomitant decrease in either amplitudes or
      latencies of SEP components. These findings suggest a modulatory role of COX-2
      products in the cerebrovascular coupling and provide evidence for existence of a
      functional metabolic buffer.

PMID- 16626974
TI  - Evidence of altered prefrontal-thalamic circuitry in schizophrenia: an optimized
      diffusion MRI study.
AB  - MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the
      diffusion tensor, was used to investigate microstructural changes in the brains
      of 12 individuals with schizophrenia compared with 12 matched control subjects.
      To control for the effects of anatomic variation between subject groups, all
      participants' diffusion images were nonlinearly registered to standard anatomical
      space. Significant statistical differences in mean diffusivity (MD) measures
      between the two groups were determined on a pixel-by-pixel basis, using Gaussian
      random field theory. We found significantly elevated MD measures within temporal,
      parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001),
      especially within the medial frontal gyrus and anterior cingulate. The dorsal
      medial and anterior nucleus of the thalamus, including the caudate, also
      exhibited significantly increased MD in the schizophrenia group (P > 0.001). This
      study has shown for the first time that MD measures offer an alternative strategy
      for investigating altered prefrontal-thalamic circuitry in schizophrenia.

PMID- 16626975
TI  - An fMRI study of the neural correlates of graded visual perception.
AB  - The neural correlates of clearly perceived visual stimuli have been reported
      previously in contrast to unperceived stimuli, but it is uncertain whether
      intermediate or graded perceptual experiences correlate with different patterns
      of neural activity. In this study, the subjective appearance of briefly presented
      visual stimuli was rated individually by subjects with respect to perceptual
      clarity: clear, vague or no experience of a stimulus. Reports of clear
      experiences correlated with activation in a widespread network of brain areas,
      including parietal cortex, prefrontal cortex, premotor cortex, supplementary
      motor areas, insula and thalamus. The reports of graded perceptual clarity were
      reflected in graded neural activity in a network comprising the precentral gyrus,
      intraparietal sulcus, basal ganglia and the insula. In addition, the reports of
      vague experiences demonstrated unique patterns of activation. Different degrees
      of perceptual clarity were reflected both in the degree to which activation was
      found within parts of the network serving a clear conscious percept, and
      additional unique activation patterns for different degrees of perceptual
      clarity. Our findings support theories proposing the involvement of a widespread
      network of brain areas during conscious perception.

PMID- 16626976
TI  - Phylogenetic relationships and phylogeography of the Killifish species of the
      subgenus Chromaphyosemion (Radda, 1971) in West Africa, inferred from
      mitochondrial DNA sequences.
AB  - We have analyzed the phylogenetic relationships of 160 specimens from 88 samples
      representing all defined species of the African Aplocheiloid subgenus
      Chromaphyosemion in order to examine the monophyly of this group, the species
      interrelationships, and to reveal trends in chromosomal evolution and formulate
      hypotheses about their evolutionary history. The data set comprised 1153 total
      nucleotides from the mitochondrial 12S rRNA, cytochrome oxidase I, and D-loop.
      The molecular-based topologies were analyzed by maximum parsimony, maximum
      likelihood, distance method and Bayesian inference support the monophyly of the
      subgenus Chromaphyosemion. All populations with ambiguous taxonomic status were
      assigned to an already described species except A. sp. Rio Muni which corresponds
      to a still undescribed species. Aphyosemion alpha and A. lugens were in basal
      position in the different trees that indicate a possible origin of the subgenus
      Chromaphyosemion in the South Cameroon-North Gabon region. Furthermore, the South
      Cameroon region (between 2 degrees and 3 degrees of North latitude) that
      accommodates half of the Chromaphyosemion species is considered to have been a
      refuge zone during the late quaternary dry events that Africa experienced.
      Phylogenetic relationships among the subgenus also revealed that chromosomal
      evolution is complex and should be studied at the intraspecific level.

PMID- 16626977
TI  - Neotomine-peromyscine rodent systematics based on combined analyses of nuclear
      and mitochondrial DNA sequences.
AB  - Recently, sequences from two nuclear genes (exon 6 of the dentin matrix protein 1
      gene and intron 7 of the beta-fibrinogen gene) and one mitochondrial gene
      (cytochrome b gene) were used independently in an attempt to resolve phylogenetic
      relationships within the neotomine-peromyscine complex. Although these studies
      provided testable hypotheses regarding this group of rodents, the affinities of
      certain tribes and genera remain uncertain. To elucidate these relationships, the
      three data partitions were tested for heterogeneity and then concatenated
      according to conditional data combination and total evidence approaches. Support
      was found for five clades, four of which correspond to well recognized tribes
      (the Neotomini, Peromyscini=Reithrodontomyini, Baiomyini, and Tylomyini).
      Recommendations are made regarding the recognition of Ochrotomys as a tribe of
      its own, the Ochrotomyini, paralleling other recent findings. The Peromyscini,
      Baiomyini, and Ochrotomyini are unresolved in relation to each other, but as a
      whole are sister to the Neotomini. The Tylomyini is basal to all clades. It
      appears that combined data from the nuclear and mitochondrial genes (analyzing
      all three partitions simultaneously) resulted in the best phylogenetic hypothesis
      regarding the complex.

PMID- 16626978
TI  - An integrated analysis of five double-blind, randomized controlled trials
      evaluating the safety and efficacy of a hyaluronan product for intra-articular
      injection in osteoarthritis of the knee.
AB  - OBJECTIVE: Five double-blind, randomized, saline-controlled trials (RCTs) were
      included in the United States marketing application for an intra-articular
      hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee.
      We report an integrated analysis of the primary Case Report Form (CRF) data from
      these trials. METHOD: Trials were similar in design, patient population and
      outcome measures - all included the Lequesne Algofunctional Index (LI), a
      validated composite index of pain and function, evaluating treatment over 3
      months. Individual patient data were pooled; a repeated measures analysis of
      covariance was performed in the intent-to-treat (ITT) population. Analyses
      utilized both fixed and random effects models. Safety data from the five RCTs
      were summarized. RESULTS: A total of 1155 patients with radiologically confirmed
      knee OA were enrolled: 619 received three or five IA-HA injections; 536 received
      "placebo" saline injections. In the active and control groups, mean ages were
      61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores
      11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a
      statistically significant reduction (P < 0.001) in total Lequesne score with
      hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: 
      0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed
      robustness of the analyses. CONCLUSIONS: This integrated analysis demonstrates
      that multiple design factors influence the results of RCTs assessing efficacy of
      intra-articular (IA) therapies, and that integrated analyses based on primary
      data differ from meta-analyses using transformed data.

PMID- 16626979
TI  - Zonal variations in the three-dimensional morphology of the chondron measured in
      situ using confocal microscopy.
AB  - OBJECTIVE: Chondrocytes in articular cartilage are surrounded by a narrow
      pericellular matrix (PCM), which together with the enclosed cell(s) are termed
      the "chondron". Although the precise function of this tissue region is unknown,
      previous studies provide indirect evidence that the PCM plays an important role
      in governing the local mechanical environment of chondrocytes. In particular,
      theoretical models of the chondron under mechanical loading suggest that the
      shape, size, and biomechanical properties of the PCM significantly influence the
      stress-strain and fluid flow environment of the cell. The goal of this study was
      to quantify the three-dimensional morphology of chondron in situ using en bloc
      immunolabeling of type VI collagen coupled with fluorescence confocal microscopy.
      METHODS: Three-dimensional reconstructions of intact, fluorescently labeled
      chondrons were made from stacks of confocal images recorded in situ from the
      superficial, middle, and deep zones of porcine articular cartilage of the medial
      femoral condyle. RESULTS: Significant variations in the shape, size, and
      orientation of chondrocytes and chondrons were observed with depth from the
      tissue surface, revealing flattened discoidal chondrons in the superficial zone,
      rounded chondrons in the middle zone, and elongated, multicellular chondrons in
      the deep zone. CONCLUSIONS: The shape and orientation of the chondron appear to
      reflect the local collagen architecture of the interterritorial matrix, which
      varies significantly with depth. Quantitative measurements of morphology of the
      chondron and its variation with site, disease, or aging may provide new insights
      into the influence of this structure on physiology and the pathology of articular
      cartilage.

PMID- 16626980
TI  - Genetic characterization of the natural hybrid species Phytophthora alni as
      inferred from nuclear and mitochondrial DNA analyses.
AB  - The different subspecies of Phytophthora alni, P. alni subsp. alni (Paa), P. alni
      subsp. uniformis (Pau), and P. alni subsp. multiformis (Pam), are recent and
      widespread pathogens of alder in Europe. They are believed to be a group of
      emergent heteroploid hybrids between two phylogenetically close Phytophthora
      species. Nuclear and mitochondrial DNA analyses were performed, using a broad
      collection of P. alni and two closely related species, P. cambivora and P.
      fragariae. Paa possesses three different alleles for each of the nuclear genes we
      studied, two of which are present in Pam as well, whereas the third matches the
      single allele present in Pau. Moreover, Paa displays common mtDNA patterns with
      both Pam and Pau. A combination of the data suggests that Paa may have been
      generated on several occasions by hybridization between Pam and Pau, or their
      respective ancestors. Pau might have P. cambivora as a species ancestor, whereas
      Pam seems to have either been generated itself by an ancient reticulation or by
      autopolyploidization.

PMID- 16626981
TI  - Bicyclic monoterpene diols stimulate release of nitric oxide from skin cells,
      increase microcirculation, and elevate skin temperature.
AB  - Bicyclic monoterpene diols (BMTd) stimulate nitric oxide synthesis in melanoma
      and neuronal cells, representing cell types arising from embryonic neural crest
      tissue. This study shows that an equimolar mixture of the BMTd's 2,3-cis/exo
      pinanediol and 2,3-cis/exo-camphanediol stimulates nitric oxide synthesis in
      epithelial cells of the skin, specifically normal human epidermal keratinocytes
      (NHEK) and normal human microvascular endothelial cells (HMVEC). A 1 mM mixture
      increased nitric oxide 3-fold in HMVEC in the first 24 h after treatment, and a 2
      mM mixture produced an equivalent increase in NHEK. We hypothesized that an
      increase in nitric oxide in skin would lead to an increase in microcirculation,
      thereby increasing skin temperature. We found that twice daily application of 1mM
      BMTd lotion significantly increased arm skin temperature by 0.5 degrees C in 14
      days compared to placebo, while a 2 mM mixture significantly increased skin
      temperature by 0.3 degrees C in 7 days (P < or = 0.05; ANOVA). A single
      application of a 2 mM BMTd mixture applied 30 min before a 30 min cold challenge
      (6 degrees C), maintained facial skin temperature 1.4 degrees C above untreated
      control sites (P < or = 0.05; ANOVA). We also tested whether BMTd treatment would
      benefit people with dark circles under their eyes. Twenty-six panelists with dark
      undereye circles completed 2-week, twice daily application of a lotion containing
      the 1mM mixture to one eye while the other eye was untreated. Seven of 26
      subjects showed a reduction of darkness of undereye circles (P < or = 0.05;
      paired t test). Application of 2 mM BMTd lotion to lips resulted in a significant
      increase in their redness, as measured by the erythema index (P < or = 0.05;
      ANOVA). These results show that a mixture of BMTd's increases nitric oxide, and
      application to skin increases microcirculation and skin temperature.

PMID- 16626982
TI  - Pomegranate juice protects nitric oxide against oxidative destruction and
      enhances the biological actions of nitric oxide.
AB  - Pomegranate juice (PJ), which is a rich source of potent flavonoid antioxidants,
      was tested for its capacity to protect nitric oxide (NO) against oxidative
      destruction and enhance the biological actions of NO. Employing chemiluminescence
      headspace analysis, PJ was found to be a potent inhibitor of superoxide anion
      mediated disappearance of NO. PJ was much more potent than Concord grape juice,
      blueberry juice, red wine, ascorbic acid, and DL-alpha-tocopherol. As little as 3
      microl of a 6-fold dilution of PJ, in a reaction volume of 5000 microl, produced
      a marked antioxidant effect, whereas 300 microl of undiluted blueberry juice or
      nearly 1000 microl of undiluted Concord grape juice were required to produce
      similar effects. PJ and other antioxidant-containing products were found to
      augment the anti-proliferative action of NO (DETA/NO) on vascular smooth muscle
      cell (rat aorta) proliferation. PJ was much more effective than the other
      products tested and elicited no effects when tested alone in the absence of added
      NO. Similarly, neither PJ nor the other products enhanced the anti-proliferative
      action of alpha-difluoromethylornithine, a stable substance that inhibits cell
      growth by NO-independent mechanisms. In order to determine whether PJ is capable
      of increasing the production of NO by vascular endothelial cells, PJ was tested
      for its capacity to upregulate and/or activate endothelial NO synthase (eNOS) in
      bovine pulmonary artery endothelial cells. PJ elicited no effects on eNOS protein
      expression or catalytic activity. Moreover, PJ did not enhance promoter activity
      in the eNOS gene (COS-7 cells transfected with eNOS). These observations indicate
      that PJ possesses potent antioxidant activity that results in marked protection
      of NO against oxidative destruction, thereby resulting in augmentation of the
      biological actions of NO.

PMID- 16626983
TI  - Oxidative stress in Perna perna and other bivalves as indicators of environmental
      stress in the Brazilian marine environment: antioxidants, lipid peroxidation and
      DNA damage.
AB  - Oxidative stress can take place in marine bivalves under a series of
      environmental adverse conditions. The study of different systems related to
      oxidative stress in these organisms can give important information about their
      physiological status and also about environmental health. Bivalves have been
      proposed as good sentinel organisms in pollution monitoring studies through the
      analysis of biochemical biomarkers, and most of the biomarkers analyzed are those
      related to oxidative stress. However, it is very important to know how other
      environmental factors not associated to the presence of pollutants might affect
      these parameters. We have studied a series of mechanisms related to oxidative
      stress in mussels which inhabit the Brazilian coast, especially in Perna perna
      species, subjected to different stress conditions, such as the exposure to
      different contaminants in the laboratory and in the field, the exposure of
      mussels to air and re-submersion, simulating the tidal oscillations, and in
      mussels collected at different seasons. Both oxidative damage levels and
      antioxidant defense systems were strongly affected by the different environmental
      stress. This review summarizes the data obtained in some studies carried out in
      bivalves from the Brazilian coast.

PMID- 16626984
TI  - Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their
      interaction with the mammalian host.
AB  - Current knowledge of the biochemistry of Trypanosoma cruzi has led to the
      development of new drugs and the understanding of their mode of action. Some
      trypanocidal drugs such as nifurtimox and benznidazole act through free radical
      generation during their metabolism. T. cruzi is very susceptible to the cell
      damage induced by these metabolites because enzymes scavenging free radicals are
      absent or have very low activities in the parasite. Another potential target is
      the biosynthetic pathway of glutathione and trypanothione, the low molecular
      weight thiol found exclusively in trypanosomatids. These thiols scavenge free
      radicals and participate in the conjugation and detoxication of numerous drugs.
      Inhibition of this key pathway could render the parasite much more susceptible to
      the toxic action of drugs such as nifurtimox and benznidazole without affecting
      the host significantly. Other drugs such as allopurinol and purine analogs
      inhibit purine transport in T. cruzi, which cannot synthesize purines de novo.
      Nitroimidazole derivatives such as itraconazole inhibit sterol metabolism. The
      parasite's respiratory chain is another potential therapeutic target because of
      its many differences with the host enzyme complexes. The pharmacological
      modulation of the host's immune response against T. cruzi infection as a possible
      chemotherapeutic target is discussed. A large set of chemicals of plant origin
      and a few animal metabolites active against T. cruzi are enumerated and their
      likely modes of action are briefly discussed.

PMID- 16626985
TI  - Body cooling and the diving capabilities of muskrats (Ondatra zibethicus): a test
      of the adaptive hypothermia hypothesis.
AB  - We tested the hypothesis that immersion hypothermia enhances the diving
      capabilities of adult and juvenile muskrats by reducing rates of oxygen
      consumption (V O2). Declines in abdominal body temperature (T(b)) comparable to
      those observed in nature (0.5-3.5 degrees C) were induced by pre-chilling animals
      in 6 degrees C water. Pre-chilling did not reduce diving V O2 of any animal
      tested in 10 degrees C or 30 degrees C water, irrespective of the nature of the
      dive. Most behavioural indices of dive performance, including average and
      cumulative dive times, were unaffected by T(b) reduction in adults, but depressed
      in hypothermic juveniles (200-400 g). Hypothermia reduced diving heart rate only
      on short (<25s) dives (16% reduction, P=0.01), but did not affect the temporal
      onset of diving bradycardia. Post-immersion V O2 was higher for pre-chilled than
      for normothermic muskrats, but the difference became insignificant on longer (>90
      s) dives. Our findings suggest that the mild hypothermia experienced by muskrats
      in nature has minimal effect on diving and post-immersion metabolic costs, and
      thus has little impact on the dive performance of this northern semi-aquatic
      mammal.

PMID- 16626986
TI  - Sleep quantitation in common marmoset, cotton top tamarin and squirrel monkey by
      non-invasive actigraphy.
AB  - Sleep quantitation data on the Neotropical primate species, apart from the
      squirrel monkey, are still sparse. As such, we have quantitated sleep in the
      common marmosets (Callithrix jacchus), cotton top tamarins (Saguinus oedipus) and
      squirrel monkeys (Saimiri sciureus) reared in one primate facility
      simultaneously, by non-invasive actigraphy. The range in total sleep time/24h
      measured for male adult common marmosets, cotton top tamarins and squirrel
      monkeys were 713-793 min (n=4), 707-889 min (n=4) and 459-475 min (n=2)
      respectively. The range in sleep episode length /12h dark phase for marmosets,
      tamarins and squirrel monkeys were 21-52 min (n=3), 10-28 min (n=4) and 9-15 min
      (n=2) respectively. Since vigilance is a critical evolutionary adaptive feature
      of predator avoidance among Callitrichid monkeys and squirrel monkeys, the
      shorter ranges in sleep episode length recorded, even under captivity, in this
      study could be interpreted as probable indicators of such vigilance behavior
      during the rest phase. We hypothesize that the vigilance behavior when it exists
      during a primate's active phase should also prevail when it is at rest (sleep).
      This hypothesis deserves additional testing in female Callitrichid monkeys.

PMID- 16626987
TI  - Opposite effects of tryptophan intake on motor activity in ring doves (diurnal)
      and rats (nocturnal).
AB  - The role of l-tryptophan as precursor of serotonin and melatonin synthesis on
      activity-rest rhythm was studied in ring doves, Streptopelia risoria, as a
      representative of diurnal animals and rats, Rattus norvegicus, as a typical
      nocturnal one. The animals were housed in cages equipped for horizontal activity
      recording in a thermostatized chamber and submitted to a 12/12h light/dark
      photoperiod (lights on at 08:00 h). After acclimatization, the animals received
      vehicle (methylcellulose) and l-tryptophan (240 mg/kg) by esophagic cannula 2h
      before the onset of either light or dark phase. Also, oral melatonin (2.5mg/kg)
      was tested for comparative purposes. After nocturnal l-tryptophan administration,
      rats showed increased activity (149%), while the opposite occurred in ring doves
      (39% decrease). No significant changes were found after diurnal l-tryptophan
      intake in either species. Melatonin produced effects similar to those of l
      tryptophan. These results suggest that the effects of l-tryptophan administration
      are dependent on the nocturnal/diurnal habits of the studied species and, most
      probably, are mediated by increased melatonin synthesis.

PMID- 16626988
TI  - Shematrin: a family of glycine-rich structural proteins in the shell of the pearl
      oyster Pinctada fucata.
AB  - Random sequencing of molecules from a cDNA library constructed from mantle mRNA
      of the pearl oyster Pinctada fucata was used to obtain information on organic
      matrix proteins in the shell. In the determined sequences, we identified 7
      distinct cDNAs encoding similar glycine-rich domains. Complete sequence analysis
      of these cDNAs showed that the predicted sequences of the proteins, which we
      named shematrins, possessed similar domains comprising repeat sequences of two or
      more glycines, followed by a hydrophobic amino acid. In addition, in shematrin-1,
      -2 and -3, a repeat domain designated as XGnX (where X is a hydrophobic amino
      acid) was conserved. It is of further note that all the shematrin proteins have
      RKKKY, RRKKY or RRRKY as their C-terminal sequence. According to northern blot
      analysis, all shematrins are exclusively expressed in the mantle, and
      particularly in the edge region of the mantle; furthermore, peptide fragments
      similar to shematrin-1 and -2 were detected in the prismatic layer of shells by
      MALDI-TOF/TOF MS analysis. These findings suggest that many of shematrins are
      synthesized in the mantle edge and secreted into the prismatic layer of the
      shell, where the protein family is thought to provide a framework for
      calcification.

PMID- 16626989
TI  - Expression of thick filament proteins during ontogenesis of the mussel Mytilus
      trossulus (Mollusca: Bivalvia).
AB  - The appearance of thick filament proteins organized into supramolecular complexes
      was studied by SDS-PAGE and Western-blot analysis at different developmental
      stages of the mussel Mytilus trossulus. Paramyosin appeared at the egg stage,
      while twitchin and myorod appeared at the blastula stage (12 h after
      fertilization). In addition, RT-PCR analysis showed that the twitchin genes were
      expressed starting from the blastula stage. Thus, the proteins forming thick
      filaments of the contractile apparatus of mussel muscles are expressed long
      before the formation of the first well-organized muscle system of the veliger
      larvae (55 h). Further, the ratios actin/myosin heavy chain (MHC) and
      paramyosin/MHC at the veliger stage (96 h) distinctly differed from those in the
      adult mussel.

PMID- 16626990
TI  - Misleading clavicular osteolytic lesion revealing fibrous dysplasia.

PMID- 16626991
TI  - Primary hypertrophic osteoarthropathy with bilateral destructive hip arthritis.

PMID- 16626992
TI  - Gait disorders in patients with fibromyalgia.
AB  - OBJECTIVES: The objective of this study was to compare gait in patients with
      fibromyalgia and in matched controls. METHODS: Measurements must be obtained in
      patients with fibromyalgia, as the evaluation scales for this disorder are semi
      quantitative. We used a patented gait analysis system (Locometrix Centaure
      Metrix, France) developed by the French National Institute for Agricultural
      Research. Relaxed walking was evaluated in 14 women (mean age 50+/-5 years; mean
      height 162+/-5 cm; and mean body weight 68+/-13 kg) meeting American College of
      Rheumatology criteria for fibromyalgia and in 14 controls matched on sex, age,
      height, and body weight. RESULTS: Gait during stable walking was severely altered
      in the patients. Walking speed was significantly diminished (P<0.001) as a result
      of reductions in stride length (P<0.001) and cycle frequency (P<0.001). The
      resulting bradykinesia (P<0.001) was the best factor for separating the two
      groups. Regularity was affected in the patients (P<0.01); this variable is
      interesting because it is independent of age and sex in healthy, active adults.
      CONCLUSION: Measuring the variables that characterize relaxed walking provides
      useful quantitative data in patients with fibromyalgia.

PMID- 16626993
TI  - Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based
      on published evidence and expert opinion.
AB  - OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate
      in rheumatoid arthritis (RA), using the evidence-based approach and expert
      opinion. METHODS: A scientific committee used a Delphi procedure to select five
      questions, which formed the basis for developing recommendations. Evidence
      providing answers to the five questions was sought in the Cochrane databases,
      PubMed, and proceedings of meetings of the French Society for Rheumatology,
      European League Against Rheumatism, and American College of Rheumatology. Using
      this evidence, a group of rheumatologists developed and validated the
      recommendations. For each recommendation, the level of evidence and the extent of
      agreement among experts were specified. RESULTS: The recommendations were as
      follows: 1: The starting dosage for methotrexate in patients with RA should not
      be less than 10 mg/week and should be determined based on disease severity and
      patient-related factors; 2: When a patient with RA shows an inadequate response
      to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20
      mg/week, according to tolerance and patient-related factors; 3: When starting
      methotrexate treatment in a patient with RA, preference should be given to the
      oral route. A switch to the intramuscular or subcutaneous route should be
      considered in patients with poor compliance, inadequate effectiveness, or
      gastrointestinal side effects; 4: At present, there is no evidence indicating
      that a change in methotrexate dosage is in order when a TNF antagonist is given
      concomitantly; 5: The investigations that are mandatory before starting
      methotrexate therapy in a patient with RA consist of a full blood cell count,
      serum transaminase levels, serum creatinine with computation of creatinine
      clearance, and a chest radiograph. In addition, serological tests for the
      hepatitis viruses B and C and a serum albumin assay are recommended. In patients
      with a history of respiratory disease or current respiratory symptoms, lung
      function tests with determination of the diffusing capacity for carbon monoxide
      are recommended; 6: Investigations that are mandatory for monitoring methotrexate
      therapy in patients with RA consist of full blood cell counts and serum
      transaminase and creatinine assays. These tests should be obtained at least once
      a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation
      can be given routinely to patients treated with methotrexate for RA. In practice,
      a minimal dosage of 5 mg of folic acid once a week, at a distance from the
      methotrexate dose, is appropriate; 8: In the event of respiratory symptoms
      possibly related to methotrexate toxicity, the drug must be stopped and symptom
      severity evaluated. Should evidence of serious disease be found, the patient
      should be admitted immediately or advice from a pulmonologist should be obtained
      immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were
      developed. These recommendations should help to improve practice uniformity and,
      ultimately, to improve the management of RA.

PMID- 16626994
TI  - Osteosarcoma presenting as a solitary focus of osteolysis in the calvarium.
AB  - Osteolysis of the skull is fairly common. The clinical presentation and results
      of laboratory or imaging tests may suggest a benign or a malignant disease.
      However, histology is the only means of obtaining a definitive diagnosis and
      should therefore be performed at the slightest doubt. We report the case of a 58
      year-old man who presented with a recent painless lump in the right
      temporoparietal region. Laboratory tests were normal. Brain imaging studies and
      total body radionuclide scanning showed no other lesions. However, the
      heterogeneous and aggressive appearance of the skull lesion prompted a surgical
      biopsy, which showed osteoblastic osteosarcoma. Chemotherapy and radiation
      therapy were given after complete excision of the tumor.

PMID- 16626995
TI  - Nonpharmacological treatments in early rheumatoid arthritis: clinical practice
      guidelines based on published evidence and expert opinion.
AB  - OBJECTIVE: To develop clinical practice guidelines for the use of
      nonpharmacological treatments in patients with early rheumatoid arthritis (RA),
      using the evidence-based approach and expert opinion. METHODS: A scientific
      committee used a Delphi prioritization procedure to select five questions.
      Evidence providing answers to the five questions was sought in the literature and
      presented to a panel of rheumatologists. The panel developed five detailed
      recommendations, filling gaps in evidence with their expert opinion. The strength
      of each recommendation was determined. RESULTS: Of the 565 publications retrieved
      by the literature review, 198 were included in the analysis. The five
      recommendations on nonpharmacological treatments for early RA were validated by a
      final vote among all participants. The recommendations are as follows: (1)
      physicians may decide to provide joint protection education to patients with
      potentially severe early RA, with the knowledge that structured joint protection
      programs have not been found effective; (2) physical exercise and sports can be
      recommended to patients with early RA; muscle strength exercises are advisable;
      (3) in patients with early RA, metatarsal pain and/or foot alignment
      abnormalities should be looked for regularly, and appropriate insoles should be
      prescribed if needed; (4) dietary measures and nutritional supplements are not
      indicated as part of the treatment of early RA; (5) elimination diets,
      particularly those with low intakes of dairy products, should be discouraged in
      patients with early RA. CONCLUSION: These recommendations should help to improve
      practice uniformity and, ultimately, to improve the management of RA.

PMID- 16626996
TI  - Effects of breath-hold diving on bone mineral density of women divers.
AB  - OBJECTIVES: The relationship between bone mineral density (BMD) and swimming has
      been thoroughly researched. The aim of this study was to determine the effects of
      breath-hold diving on the BMD in the proximal femurs of women divers. METHODS: A
      case-control observational study was carried out using health-checks of divers
      and control subjects at a hospital in Jeju City, South Korea. Women divers (N=61)
      were matched individually with non-diver controls (N=61) by age, weight, and
      postmenopausal year. The bone mineral densities of their proximal femurs (total
      hip, femoral neck) were assessed by dual-energy X-ray absorptiometry. RESULTS:
      The average diving year of women divers was 34+/-13 years. The BMD of divers was
      higher than that of controls in the total hip and femur neck area (P<0.05). On
      multiple linear regression analysis, age and body weight were predictors of
      proximal femur bone mineral densities in divers. On linear regression analysis of
      the proximal femur BMD according to age in divers and controls, the bone mineral
      densities of divers tend to decrease more rapidly than those of controls in all
      two areas of the proximal femurs. CONCLUSIONS: Our study results may suggest that
      diving in a high-pressure environment is an osteogenic stimulus. However, the
      weight-supported environment in diving exerts an effect that reduces BMD
      proportionately to the time spent in the water.

PMID- 16626997
TI  - DRESS syndrome induced by sulphasalazine in rheumatoid arthritis.

PMID- 16626998
TI  - Bilateral fibrous ankylosis of temporomandibular joint associated with ankylosing
      spondylitis: a case report.

PMID- 16626999
TI  - Hand involvement in Behcet's disease.
AB  - AIMS: To study the clinical hand findings in Behcet's disease (BD) and to observe
      scintigraphic changes of these areas. METHODS: Fifty-seven randomly selected BD
      patients and the patients in the control group (N=40) were evaluated by two blind
      rheumatologists. The hands were examined for the presence of pain, tenderness,
      swelling, effusion, erythema, warmth, range of motion and limitation of motion,
      deformities and muscle atrophy. Then scintigraphic examination of the hands was
      performed. Control hand scintigrams were obtained from 40 age- and sex-matched
      patients and were examined by the same two observers. RESULTS: Thirty-two of the
      57 patients (56.1%) showed Behcet's clinical hand findings. Terminal phalangeal
      pulp atrophy was observed in 17 (29.81%), rheumatoid-like hand findings were
      observed in 16 (28.1%), dorsal interosseos atrophy was observed in 12 (20.05%)
      and erythema over the digits was observed in 12 (20.05%). Twenty-four patients
      (42.1%) had scintigraphic involvement. The disease duration was observed to be an
      important factor for hand findings (P=0.040) and scintigraphic involvement
      (P=0.011). CONCLUSION: High prevalence of hand involvement in BD and its
      relationship with disease duration is demonstrated. Hand involvement tends to be
      overlooked and careful examination is required in the evaluation of BD. The
      scintigraphic involvement detected in hands requires special consideration, too.

PMID- 16627000
TI  - [Primary ovarian abscess. Diagnosis and therapeutic approach].
AB  - Primary ovarian abscess is a rare infection. A new case has led us to carry out a
      literature review in order to optimize the treatment. Exceptionally isolated,
      primary ovarian abscess usually belongs to the postoperative complications.
      Nevertheless, its etiopathogenies are numerous. The symptoms are often poor;
      therefore the diagnosis is difficult to establish. The curative treatment must
      associate surgery and antibiotherapy. Even if laparoscopic surgery is the first
      line treatment in many cases, laparotomy remains the choice procedure.
      Ultrasonographically-guided evacuation has to be further evaluated. Preventive
      treatment is of major importance.

PMID- 16627001
TI  - Allobilharzia visceralis gen. nov., sp. nov. (Schistosomatidae-Trematoda) from
      Cygnus cygnus (L.) (Anatidae).
AB  - In Iceland, the examination of whooper swans (Cygnus cygnus L.) viscera resulted
      in the detection of adult digenean flukes of the family Schistosomatidae. The
      mature worms occurring in the blood vessels of the large intestine and
      mesenterium caused vascular lesions, around the eggs deposited in the intestinal
      mucosa and liver granulomatous reactions developed. The morphology of the
      isolated schistosomes shows certain similarity with the flukes of the genus
      Trichobilharzia; in males reduced gynecophoral canal, and on both sexes both
      suckers and spatulate ends are present. However, the Icelandic flukes possess
      other morphological features which are distinct from the genus: the point of
      caecal reunion in males takes place posterior to gynecophoral canal and the
      genital pore is behind acetabulum and anterior to caecal reunion. In order to
      evaluate the identity of Icelandic schistosomes, sequencing of ITS region of DNA
      was performed, and the obtained sequence was deposited in GenBank under the
      accession no. DQ067561. Following phylogenetic analysis of relationship between
      the sequence of Icelandic flukes and database sequences of other bird schistosome
      genera (Trichobilharzia, Gigantobilharzia and Dendritobilharzia) showed different
      position of Icelandic worms in the phylogenetic tree. In conclusion, our study
      revealed new genus and species of schistosome flukes--Allobilharzia visceralis
      gen. et sp. n.

PMID- 16627002
TI  - Phospholipid homeostasis in phosphatidylserine synthase-2-deficient mice.
AB  - Phosphatidylserine (PS) is synthesized in mammalian cells by two distinct serine
      exchange enzymes, phosphatidylserine synthase-1 and -2. We recently demonstrated
      that mice lacking PS synthase-2 develop normally and exhibit no overt
      abnormalities [Bergo et al., (2002) J. Biol. Chem. 277:47701-47708]. We now show
      that PS synthase-2 mRNA levels are up to 80-fold higher in livers of embryos than
      in adults. Despite reduced serine-exchange activity in several tissues of PS
      synthase-2 deficient mice, the phospholipid composition of mitochondria and
      microsomes from these tissues is normal. Although PS synthase-2 is highly
      expressed in neurons, axon extension of cultured sympathetic neurons is not
      impaired by PS synthase-2 deficiency. We hypothesized that mice compensate for PS
      synthase-2 deficiency by modifying their phospholipid metabolism. Our data show
      that the rate of PS synthesis in hepatocytes is not reduced by PS synthase-2
      deficiency but PS synthase-1 activity is increased. Moreover, PS degradation is
      decreased by PS synthase-2 deficiency, probably as a result of decreased PS
      degradation via phospholipases rather than decreased PS decarboxylation. These
      experiments underscore the idea that cellular phospholipid composition is tightly
      controlled and show that PS synthase-2-deficient hepatocytes modify phospholipid
      metabolism by several compensatory mechanisms to maintain phospholipid
      homeostasis.

PMID- 16627003
TI  - Coronary artery bypass graft operation: Patients' experience of health and well
      being over time.
AB  - BACKGROUND: The aim of the coronary artery bypass graft operation is to relieve
      anginal symptoms and improve functional ability, quality of life and survival.
      However, having the surgery does not always have the desired outcomes. Although
      numerous studies have investigated the outcomes of coronary artery bypass graft
      operation, little attention has been given to patients' perceptions of the
      outcomes or effects of the operation on health and well-being over time. AIM: To
      explore patients' perspectives on the effects of coronary artery bypass surgery
      on health and well-being over time. METHODS: As part of a larger mixed methods
      study, 62 in-depth audio-taped interviews with men and women who had undergone
      coronary artery bypass approximately 7 years earlier were conducted. Interviews
      were audio-taped and transcribed. Data were analysed thematically. This paper
      reports the findings from the qualitative component of the larger study.
      FINDINGS: The four main themes: 'Recovery and Rehabilitation', 'Seven Years On',
      'Maintaining a Positive Approach', and 'Health Behaviour Change' reflect the main
      areas of focus emerging across the interviews and provide credible overarching
      descriptors of the sub-themes they encompass. The 11 sub-themes identified were
      recognised as central to the patients' experiences of their health and well-being
      over the longer-term. CONCLUSIONS: Although most patients report improved health
      and well-being after coronary artery bypass operation, many have described their
      recovery and rehabilitation as a complex process with both short and long term
      effects. The insights provided by participants help improve our understanding of
      the impact of the operation on patients' health and well-being over time. We
      believe these insights will help us to anticipate the possible needs of future
      patients and enable us develop appropriate interventions that may facilitate self
      management for optimal recovery and health maintenance.

PMID- 16627004
TI  - Recombinant adenoviral vectors turn on the type I interferon system without
      inhibition of transgene expression and viral replication.
AB  - Recombinant adenovirus administration gives rise to transgene-independent effects
      caused by the ability of the vector to activate innate immunity mechanisms. We
      show that recombinant adenoviruses encoding reporter genes trigger IFN-alpha and
      IFN-beta transcription from both plasmacytoid and myeloid mouse dendritic cells.
      Interestingly, IFN-beta and IFN-alpha5 are the predominant transcribed type I IFN
      genes both in vitro and in vivo. In human peripheral blood leukocytes type I IFNs
      are induced by adenoviral vectors, with a preponderance of IFN-beta together with
      IFN-alpha1 and IFN-alpha5 subtypes. Accordingly, functional type I IFN is readily
      detected in serum samples from human cancer patients who have been treated
      intratumorally with a recombinant adenovirus encoding thymidine kinase. Despite
      inducing functional IFN-alpha release in both mice and humans, gene transfer by
      recombinant adenoviruses is not interfered with by type I IFNs either in vitro or
      in vivo. Moreover, IFN-alpha does not impair replication of wild-type adenovirus.
      As a consequence, cancer gene therapy strategies with defective or replicative
      competent adenoviruses are not expected to be hampered by the effect of the type
      I IFNs induced by the vector itself. However, type I IFN might modulate antitumor
      and antiadenoviral immune responses and thus influence the outcome of gene
      immunotherapy.

PMID- 16627005
TI  - Differential action of proteases from Trimeresurus malabaricus, Naja naja and
      Daboia russellii venoms on hemostasis.
AB  - The action of venom proteases and their role in hemostasis has been compared in
      the venoms of Trimeresurus malabaricus, Daboia russellii and Naja naja from the
      Southern region of Western Ghats, India. These venoms exhibit varying amounts of
      proteolytic activity and also influence hemostasis differently. Casein
      hydrolyzing activity of T. malabaricus venoms was 16 and 24 fold higher than
      those of N. naja and D. russellii venoms, respectively. With the synthetic
      substrate TAME, the highest activity was observed in T. malabaricus venom. N.
      naja venom did not hydrolyze TAME even at higher concentrations. These variations
      in proteolytic activity also influenced the coagulation process. T. malabaricus
      and D. russellii venoms are strongly procoagulant and reduce the re-calcification
      time from 148 to 14 and 12 s, respectively. Similarly, both T. malabaricus and D.
      russellii venoms reduce the prothrombin time from 12.5 to 6.0 s. On the other
      hand, N. naja venom is anticoagulant and prolongs re-calcification time to 600 s
      and prothrombin time to 42 s. In spite of varied effects on hemostasis, all the
      venoms hydrolyze fibrinogen. T. malabaricus venom hydrolyses both Aalpha and
      Bbeta subunits. While D. russellii and N. naja venoms hydrolyse only Aalpha. None
      of these venoms hydrolyze the gamma subunit of fibrinogen. Inhibition studies
      with specific protease inhibitors revealed that both N. naja and T. malabaricus
      venoms contain only metalloproteases. D. russellii venom contained both serine
      and metalloproteases. Only, T. malabaricus venom exhibited thrombin-like activity
      and induces fibrin clot formation with purified fibrinogen within 58 s. Even
      though D. russellii venom exhibits procoagulant activity, it did not show
      thrombin-like activity and may act on other coagulation factors.

PMID- 16627006
TI  - Cadmium and zinc induction of ZnT-1 mRNA in an established carp cell line.
AB  - The cDNA of a zinc transporter-1 (ZnT-1) gene was cloned from an established cell
      line derived from common carp (Cyprinus carpio) using rapid amplification of cDNA
      ends (RACE). Using real-time quantitative PCR, we showed that both zinc (Zn) and
      cadmium (Cd) transiently upregulate ZnT-1 mRNA to comparable levels. The loosely
      bound cellular Zn pool, as estimated using the Zn-specific probe FluoZin-3, was
      increased threefold after exposure to 250 microM ZnCl(2). Correspondingly, the
      ZnT-1 mRNA level at 24 h was induced about fivefold, reflecting the need for more
      zinc export capacity. Total cellular zinc levels were not different from the
      controls after 72 h of exposure to 10, 50, or 250 microM ZnCl(2). A loss of total
      cellular Zn but little labile zinc changes were observed with up to 25 microM Cd.
      At 72 h, the total Zn was partially restored to the control levels, only 1 microM
      Cd allowed for a full recovery. Downregulation of ZnT-1 mRNA and partial loss of
      loosely bound Zn were observed with 50 microM Cd. Our results clearly show that
      although Zn and Cd can both regulate Zn export in EPC cells, the effects on the
      cellular Zn pools are quite different.

PMID- 16627007
TI  - The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a
      randomized trial of Ginkgo biloba extract in prevention of dementia.
AB  - The epidemic of late life dementia, prominence of use of alternative medications
      and supplements, and initiation of efforts to determine how to prevent dementia
      have led to efforts to conduct studies aimed at prevention of dementia. The GEM
      (Ginkgo Evaluation of Memory) study was initially designed as a 5-year,
      randomized double-blind, placebo-controlled trial of Ginkgo biloba, administered
      in a dose of 120 mg twice per day as EGb761, in the prevention of dementia (and
      especially Alzheimer's disease) in normal elderly or those with mild cognitive
      impairment. The study anticipates 8.5 years of participant follow-up. Initial
      power calculations based on estimates of incidence rates of dementia in the
      target population (age 75+) led to a 3000-person study, which was successfully
      recruited at four clinical sites around the United States from September 2000 to
      June 2002. Primary outcome is incidence of all-cause dementia; secondary outcomes
      include rate of cognitive and functional decline, the incidence of cardiovascular
      and cerebrovascular events, and mortality. Following screening to exclude
      participants with incident dementia at baseline, an extensive neuropsychological
      assessment was performed and participants were randomly assigned to treatment
      groups. All participants are required to have a proxy who agreed to provide an
      independent assessment of the functional and cognitive abilities of the
      participant. Assessments are repeated every 6 months. Significant decline at any
      visit, defined by specific changes in cognitive screening scores, leads to a
      repeat detailed neuropsychological battery, neurological and medical evaluation
      and MRI scan of the brain. The final diagnosis of dementia is achieved by a
      consensus panel of experts. Side effects and adverse events are tracked by
      computer at the central data coordinating center and unblinded data are reviewed
      by an independent safety monitoring board. Studies such as these are necessary
      for this and a variety of other potential protective agents to evaluate their
      effectiveness in preventing or slowing the emergence of dementia in the elderly
      population.

PMID- 16627008
TI  - Immersion of the hand in ice water releases adrenergic vasoconstrictor tone in
      the ipsilateral temple.
AB  - Immersion of the hand in painfully cold water induces cutaneous vasodilatation in
      the temples, more so ipsilaterally than contralaterally. To investigate the
      mechanism of this response, guanethidine or saline was administered by
      transcutaneous iontophoresis to a recording site in the temple of ten
      participants before they immersed one of their hands in ice water. Guanethidine
      displaces noradrenaline from sympathetic nerve terminals and inhibits sympathetic
      noradrenergic neurotransmission. Therefore, it was hypothesized that guanethidine
      pre-treatment would block vasodilatation mediated by release of sympathetic
      vasoconstrictor tone in cutaneous vessels in the temple. During hand immersion,
      increases in the amplitude of the pulse waveform detected by laser Doppler
      flowmetry were greater in the ipsilateral than contralateral temple (86% vs. 34%
      above baseline, p<0.05), and pre-treatment with guanethidine prevented this
      asymmetric response (ipsilateral response 21% above baseline and contralateral
      response 32%, difference not significant). Guanethidine also inhibited
      ipsilateral increases in cutaneous blood flow during hand immersion in responsive
      participants. These findings suggest that limb pain inhibited ipsilateral
      adrenergic vasoconstrictor outflow in the temple. Thus, the findings challenge
      the concept of the sympathetic nervous system as a "mass action" system that
      discharges in unison to meet environmental demands. Instead, they suggest that
      the sympathetic nervous system is highly differentiated, with separate control of
      discrete reflex pathways on each side of the body.

PMID- 16627009
TI  - Spontaneous electrical activity in the prostate gland.
AB  - The cellular mechanisms that underlie the initiation, maintenance and propagation
      of electrical activity in the prostate gland remain little understood.
      Intracellular microelectrode recordings have identified at least two distinct
      electrical waveforms: pacemaker potentials and slow wave activity. By analogy
      with the intestine, we have proposed that pacemaker activity arises from a
      morphologically distinct group of c-Kit positive interstitial cells that lie
      mainly between the glandular epithelium and smooth muscle layers. We speculate
      that pacemaker activity arising from the prostatic interstitial cells (PICs) is
      likely to propagate and initiate slow wave activity in the smooth muscle cells
      resulting in contraction of the stromal smooth muscle wall. While spontaneous
      electrical activity in the prostate gland is myogenic in origin, it is clear that
      nerve-mediated agents are able to modulate this activity. Excitatory agents such
      as histamine, phenylephrine and a raised potassium saline all increase slow wave
      discharge. In contrast, nitric oxide donors reduce or abolish the spontaneous
      electrical events. However, the cellular mechanisms underlying the action of
      various endogenously released agents remain to be elucidated.

PMID- 16627011
TI  - Differential effects of plasma membrane electric excitation on H+ fluxes and
      photosynthesis in characean cells.
AB  - Cells of characean algae exposed to illumination arrange plasma-membrane H(+)
      fluxes and photosynthesis in coordinated spatial patterns (bands). This study
      reveals that H(+) transport and photosynthesis patterns in these excitable cells
      are affected not only by light conditions but also by electric excitation of the
      plasma membrane. It is shown that generation of action potential (AP) temporally
      eliminates alkaline bands, suppresses O(2) evolution, and differentially affects
      primary reactions of photosystem II (PSII) in different cell regions. The quantum
      yield of PSII electron transport decreased after AP in the alkaline but not in
      acidic cell regions. The effects of electric excitation on fluorescence and the
      PSII electron flow were most pronounced at light-limiting conditions. Evidence
      was obtained that the shift in chlorophyll fluorescence after AP is due to the
      increase in DeltapH at thylakoid membranes. It is concluded that the AP-triggered
      pathways affecting ion transport and photosynthetic energy conversion are linked
      but not identical.

PMID- 16627012
TI  - Impaired gastric myolectrical activity in patients with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is frequently associated with gastrointestinal
      complaints that can be due to gastrointestinal dysmotility. Electrogastrography
      (EGG) is an attractive, non-invasive procedure to assess gastric electric
      activity. The aims of our study were to investigate EGG abnormalities in
      pancreatic sufficient and pancreatic insufficient CF patients, and to examine
      whether EGG correlates with gastric emptying as assessed by scintigraphy.
      METHODS: EGG was performed in 23 CF patients (12 pancreatic sufficient patients,
      11 pancreatic insuffficient) by using cutaneous recording pre- and postprandialy.
      Pre- and postpostprandial EGG indexes were compared to 19 healthy control
      patients. Gastric emptying was assessed simultaneously by gastric scintigraphy in
      11 of the 23 CF patients. Six patients underwent a repeated scintigraphy
      recording following a month of treatment with cisapride. RESULTS: Abnormal
      patterns of EGG were found in 78.3% of CF patients compared to 31.3% of controls
      during fasting (p<or=0.003) and in 56.5% of CF patients compared to 15.7% in
      healthy controls postprandially (p<or=0.018). In the CF patients, dysmotility
      consisted mostly of bradygastria during both fasting (16 of 18 with abnormal EGG)
      and postprandially (12 of 13 [92.3%]). Gastric emptying results on scintigraphy
      were in agreement with EGG results in 9 of 11 (two normal and seven
      pathological). Five of the six patients treated with cisapride (83.3%) showed
      significant improvement in EGG indexes. CONCLUSIONS: Our results suggest that EGG
      abnormalities are frequently found in CF patients. The similar rate of EGG and
      gastric scintigraphy abnormalities suggests that EGG may be a useful clinical
      tool in CF patients.

PMID- 16627010
TI  - New methods for inferring population dynamics from microbial sequences.
AB  - The reduced cost of high throughput sequencing, increasing automation, and the
      amenability of sequence data for evolutionary analysis are making DNA data (or
      the corresponding amino acid sequences) the molecular marker of choice for
      studying microbial population genetics and phylogenetics. Concomitantly, due to
      the ever-increasing computational power, new, more accurate (and sometimes
      faster), sequence-based analytical approaches are being developed and applied to
      these new data. Here we review some commonly used, recently improved, and newly
      developed methodologies for inferring population dynamics and evolutionary
      relationships using nucleotide and amino acid sequence data, including:
      alignment, model selection, bifurcating and network phylogenetic approaches, and
      methods for estimating demographic history, population structure, and population
      parameters (recombination, genetic diversity, growth, and natural selection).
      Because of the extensive literature published on these topics this review cannot
      be comprehensive in its scope. Instead, for all the methods discussed we
      introduce the approaches we think are particularly useful for analyses of
      microbial sequences and where possible, include references to recent and more
      inclusive reviews.

PMID- 16627013
TI  - Paternity in men with cystic fibrosis: a retrospective survey in France.
AB  - BACKGROUND: Because more patients reach adulthood, new questions as "what about
      having a child and/or paternity responsibility?" arose. METHOD: We performed a
      retrospective investigation based on the French CF registry. The context of the
      paternity and the health status of fathers were recorded. A comparison with
      clinical status of non-father patients and a compilation of follow-up data to
      evaluate its impact were done. RESULTS: Forty-eight men had 69 children. One
      fourth was said to be natural conceptions, 69% needed assisted reproduction
      techniques. No child had CF. Clinical status of men was satisfactory: mean BMI
      was 20.9 kg/m(2) and mean FEV(1) and FVC were 50.5% and 69.2% of predicted,
      respectively. When matched to CF non-fathers, few significant differences
      appeared. More non-fathers were F508del/F508del (p=0.03). Fathers' sputum
      cultures were positive for non-Pseudomonas aeruginosa strain (p=0.05), including
      Staphylococcus aureus (p=0.01). Mean age at diagnosis was higher, and based on
      minor evidence of sterility as first symptom leading to the diagnosis of CF
      (p=0.01) or aspergillosis (p=0.03). The 3-year follow-up showed no degradation of
      the clinical status. CONCLUSION: Men having paternity responsibility over
      children did not differ from the CF male population and neither did it seem to
      have an impact on the disease course.

PMID- 16627014
TI  - NMR studies of BPTI aggregation by using paramagnetic relaxation reagents.
AB  - Paramagnetic probes, whose approach to proteins can be monitored by nuclear
      magnetic resonance (NMR) studies, have been found of primary relevance for
      investigating protein surfaces accessibility. Here, paramagnetic probes are also
      suggested for a systematic investigation on protein aggregation. Bovine
      pancreatic trypsin inhibitor (BPTI) was used as a model system for aggregation by
      analyzing its interaction with TEMPOL and Gd(III)DTPA-BMA. Some of the measured
      paramagnetic relaxation rates of BPTI protons exhibited a reverse dependence on
      protein concentration, which can be attributed to the formation of transient BPTI
      aggregates.

PMID- 16627015
TI  - Early bacterial infection of the pancreas and course of disease in cerulein
      induced acute pancreatitis in rats.
AB  - BACKGROUND: Bacterial infection of the pancreas aggravates the course of acute
      pancreatitis. Since bacterial translocation from the gut is likely to be an early
      event, in an animal model of pancreatitis, we investigated the effect of early
      bacterial supra-infection of the pancreas on the course of the disease. METHODS:
      Six hours after the induction of acute pancreatitis in male Wistar rats (n = 180)
      by supramaximal stimulation with cerulein (or placebo in a control group), the
      animals were operated and a suspension of Helicobacter pylori, Escherichia coli
      or saline were introduced either in the pancreatic duct or interstitium (12
      groups of 15 rats each); after 24 h, animals were killed and the following
      parameters analysed: macroscopic and histologic appearance of the pancreas
      (score), wet-to-dry weight ratio, pancreas trypsinogen activation peptide level,
      serum amylase, interleukin-6 and phospholipase A2 activity. RESULTS: All
      parameters were increased in rats with cerulein-induced pancreatitis in
      comparison to placebo. Interstitial and intraductal application of bacteria
      increased the pancreatic damage. This effect was more evident with the
      application of E. coli in both cerulein and placebo groups. Application of E.
      coli but not of H. pylori determined pancreatic activation of trypsinogen,
      increased mortality and induced the production of interleukin-6. CONCLUSIONS:
      Bacterial invasion of the pancreas worsens the histologic and clinical picture of
      disease and induces a systemic inflammatory response.

PMID- 16627016
TI  - Pathophysiological characteristics of the various forms of gastro-oesophageal
      reflux disease. Spectrum disease or distinct phenotypic presentations?
AB  - BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a
      spectrum disease has recently been criticised and the distinct phenotypic
      presentations model has been proposed. AIM: To evaluate the main
      pathophysiological characteristics of various gastro-oesophageal reflux disease
      presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were
      performed in a gastro-oesophageal reflux disease series collected in a 7-year
      period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total
      percentage acid reflux time was significantly higher in long-segment Barrett's
      oesophagus and in ulcerative oesophagitis than in all the other gastro
      oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus
      results were quite similar to those found in non-erosive reflux disease and in
      erosive reflux disease. Patients with ulcerative oesophagitis and long-segment
      Barrett's oesophagus were older than all the other gastro-oesophageal reflux
      disease groups. The mean lower oesophageal sphincter pressure was significantly
      reduced in non-erosive reflux disease, erosive reflux disease, ulcerative
      oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's
      oesophagus as compared with functional heartburn and hypersensitive oesophagus
      and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro
      oesophageal reflux disease, severity of acid reflux increases from non-erosive
      reflux disease through erosive reflux disease up to ulcerative oesophagitis and
      long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment
      Barrett's oesophagus could represent an advanced step in the natural history of
      gastro-oesophageal reflux disease. Our results do not confirm the distinct
      phenotypic presentations hypothesis.

PMID- 16627017
TI  - Endoanal ultrasound in perianal fistulas and abscesses.
AB  - Anal ultrasound has demonstrated to be accurate in staging perianal
      cryptoglandular fistulae and fistulae in Crohn's disease. When there is an
      external fistula opening, H2O2 can be introduced with a plastic infusion
      catheter. The tract becomes then visible as a hyperechoic lesion ('white'). It
      has been shown that this corresponds excellent with surgical findings. It is
      equally sensitive as endoanal MRI. Because recurrent cryptoglandular fistulae are
      complex in about 50% and Crohn's fistula in 75%, it is mandatory to perform anal
      ultrasound preoperative in these patients to avoid missed tracks during surgery
      and subsequent recurrences. Anal ultrasound can also be used to monitor (medical)
      therapy in patients with Crohn's disease. Especially considering the easiness of
      performing and lesser costs then MRI, endoanal ultrasound merits more attention.

PMID- 16627018
TI  - Malignancies and mortality in patients with coeliac disease and dermatitis
      herpetiformis: 30-year population-based study.
AB  - BACKGROUND AND AIM: To assess the long-term risks of malignant diseases and
      mortality in patients with coeliac disease and dermatitis herpetiformis in a
      centre, where the prevalence of these diseases is high. The risks have probably
      been overestimated, as patients with subtle forms have earlier remained
      undetected. PATIENTS: The study comprised 17,245 person-years of follow-up in
      1147 patients. METHODS: The observed numbers of malignancies and causes of deaths
      were assessed, and compared to those expected, and standardised incidence ratio
      and standardised mortality ratio given. RESULTS: The occurrence of all malignant
      conditions was equal to that in the population both in coeliac disease and
      dermatitis herpetiformis: standardised incidence ratios of 1.2 (95% confidence
      intervals 0.9-1.5) and 1.0 (0.6-1.5), respectively. Five patients with coeliac
      disease and seven with dermatitis herpetiformis had developed non-Hodgkin
      lymphoma; standardised incidence ratios of 3.2 (1.0-7.5) and 6.0 (2.4-12.4),
      respectively. Four patients with coeliac disease and one with dermatitis
      herpetiformis had enteropathy-associated T-cell lymphoma, associated with
      inadequate dietary compliance. Mortality was increased (standardised mortality
      ratio 1.26; 1.00-1.55) in coeliac disease, but decreased in dermatitis
      herpetiformis (standardised mortality ratio 0.52; 0.36-0.72). CONCLUSION: The
      overall prognosis in our patients was good. Non-Hodgkin lymphoma emerged in
      patients with undiagnosed or poorly treated coeliac disease. The mortality rate
      in dermatitis herpetiformis was even lower than in the population. Our data
      support the early diagnosis and dietary treatment of these conditions.

PMID- 16627019
TI  - Pharmacological management of pain in chronic pancreatitis.
AB  - Pain is the major presenting symptom of chronic pancreatitis. Patients with
      chronic pancreatitis experience substantial impairments in health-related quality
      of life. Pain may be considered as the most important factor affecting the
      quality of life. The pathogenesis of pancreatic pain is poorly understood. The
      cause of pain in chronic pancreatitis is probably multifactorial. This article
      discusses the various hypotheses that have been suggested to underlie pain.
      Special attention is paid to the concept of autonomous central sensitisation and
      hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step
      of chronic pancreatic pain management. As a second step, it is important to
      exclude treatable complications of chronic pancreatitis, such as pseudocysts.
      Symptomatic treatment with analgesics is often unavoidable in patients with
      chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and
      eventually opioids are suitable. Several trials have been performed with
      pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in
      terms of pain relief. The treatment of chronic pancreatic pain requires a
      multidisciplinary approach that tailors the various therapeutic options to meet
      the need of the individual patient.

PMID- 16627020
TI  - The clinical value of hepatocyte growth factor and its receptor--c-met for liver
      cancer patients with hepatectomy.
AB  - BACKGROUND: To study the dynamic change of hepatocyte growth factor after
      hepatectomy in patients with primary liver cancer, and to analyse the prognostic
      value of hepatocyte growth factor and c-met for these patients. METHODS: Thirty
      one consecutive patients undergoing partial hepatectomy for liver cancer were
      studied. Serum hepatocyte growth factor level was determined by using enzyme
      linked immunosorbent assay kit before and after operation, respectively. C-met
      protein and MRNA expressions in cancerous and paracancerous tissues were examined
      by immunohistochemical and RT-PCR methods, respectively. The correlations between
      clinical-pathologic parameters and the expressions of hepatocyte growth factor in
      serum and c-met in cancerous tissues were analysed, respectively. RESULTS: Liver
      cancer patients had a significantly higher level of serum hepatocyte growth
      factor than normal controls (1.0424+/-0.498 ng/ml versus 0.685+/-0.115 ng/ml,
      p=0.008). Serum hepatocyte growth factor level was positively affected by tumour
      size, node cirrhosis, portal vein tumour thrombi, cholangiocarcinoma (including
      combined hepatocellular carcinoma), poorly differentiated hepatocellular
      carcinoma and tumour recurrence or metastases. After hepatectomy, serum
      hepatocyte growth factor level peaked on the third postoperative day, and then
      declined, but did not return to normal level on the postoperative day 10. From
      the preoperative day to postoperative day 10, the level of serum hepatocyte
      growth factor had a decrease of percent (85.33+/-10.2%) in the group with large
      tumours (>5 cm), but an elevation of percent (121.9+/-10.3%) in the group with
      small tumours (<or=5 cm). From the preoperative day to postoperative day 3, the
      level of serum hepatocyte growth factor had a higher elevation in the group with
      major resection than in the group with local resection (p=0.016). Moderately or
      strongly positive expression of c-met protein was observed in 27 cancerous
      regions (27/31), and only in 5 paracancerous regions. The intensive expression of
      c-met MRNA was 100% (31/31) detectable in the cancerous tissues, but only 22.6%
      (7/31) in the paracancerous tissues. C-met protein expression in cancerous
      tissues was correlated with portal vein tumour thrombi, cholangiocarcinoma and
      tumour recurrence or metastases, and the expression in paracancerous tissues was
      correlated with node cirrhosis. No significant correlation was observed between
      the hepatocyte growth factor in serum and c-met in cancerous tissues. CONCLUSION:
      The over-expressions of the hepatocyte growth factor and c-met indicates an
      adverse prognosis for patients with liver cancer. The sustained high level of
      serum hepatocyte growth factor after hepatectomy may be a factor related to early
      tumour recurrence and metastasis. Liver regeneration may be a main factor leading
      to high level of serum hepatocyte growth factor in early postoperative stage.

PMID- 16627021
TI  - Hepatitis C virus infection in a resident elderly population: a 10-year follow-up
      study.
AB  - BACKGROUND: The natural history of hepatitis C virus infection in the elderly is
      poorly known. OBJECTIVE: To assess the mortality rate, the progression of liver
      disease, the hepatitis C virus carrier state and the co-morbidity in a cohort of
      35 out of 1,063 anti-hepatitis C virus positive elderly people prospectively
      followed-up from 1992 to 2002. METHODS: Liver function tests, hepatitis C virus
      RNA analysis, hepatitis C virus genotyping and abdominal ultrasonography were
      assessed at the beginning of the study, and then, liver function tests and
      ultrasonography were performed annually during the first 5 years of the follow
      up. At the end of the 10-year period, causes of death were recorded, while
      surviving patients underwent again medical examination, liver function tests and
      abdominal ultrasonography. RESULTS: Out of 35 patients with a 10-year follow-up,
      12 patients died: only 2 (5.7%) from liver-related disease (hepatocellular
      carcinoma and liver failure), whilst 10 (28.5%) from extrahepatic causes. Out of
      the two patients dying from liver-related causes, one was hepatitis C virus-RNA
      positive and one hepatitis C virus-RNA negative. Among the 23 living patients, 13
      were hepatitis C virus-RNA positive (56.5%), the majority being infected with
      genotype 2 (69%); of them, 6 (46.1%) had persistently normal alanine
      aminotransferase levels. None of the hepatitis C virus-RNA positive individuals
      had excessive alcohol intake. CONCLUSION: Despite the presumably long duration of
      infection in our cohort, the liver-related mortality was five-fold lower than
      that from extrahepatic causes (five-fold higher). Lack of hepatic co-morbidity
      factors, such as alcohol consumption, seems to be relevant for the limited
      severity of liver disease.

PMID- 16627022
TI  - Use of upper endoscopy to evaluate patients with a positive faecal occult blood
      test and negative colonoscopy: is it appropriate?

PMID- 16627023
TI  - Follow-up after surgical treatment for cancer of the gastrointestinal tract.
AB  - BACKGROUND: Presently, no evidence-based guidelines for the follow-up of patients
      after surgery for gastrointestinal cancer are available. As a consequence, follow
      up strategies may differ between hospitals depending on preference of physicians.
      We investigated which follow-up procedures are currently employed after surgery
      for gastrointestinal cancer in the Netherlands. METHOD: A questionnaire was sent
      to all surgical departments in the Netherlands. The questionnaire focused on
      frequency of follow-up visits and diagnostic procedures after surgical treatment
      for oesophageal, gastric, pancreatic and colorectal cancer and psychosocial
      issues during follow-up. RESULTS: The response rate was 90% (83/92). In the
      majority of hospitals, surgeons treated patients with colorectal (100%) and
      gastric (96%) cancer in their own centre, whereas patients with pancreatic (64%)
      and oesophageal (61%) cancer were more often referred to a tertiary centre. For
      all patients treated for gastrointestinal cancer, three to four follow-up visits
      were made in the first year, followed by at least two annual visits thereafter.
      After colorectal surgery, blood tests (78%), colonoscopy (75%) and abdominal
      ultrasound (57%) were frequently performed. In other gastrointestinal
      malignancies, procedures were in most cases only performed if symptoms occurred.
      In almost three-quarters of patients, psychosocial problems were observed, which
      were dealt with by surgeons in two-thirds of patients. The majority of patients
      treated for gastrointestinal cancer were pre- and postoperatively discussed in a
      multidisciplinary setting. Oncologists, gastroenterologists and dieticians were
      the most frequently consulted specialists after surgery for gastrointestinal
      cancer. CONCLUSION: Patients frequently visit the outpatient clinic after surgery
      for gastrointestinal cancer in the Netherlands. Whereas follow-up after
      colorectal cancer surgery focuses on finding recurrent disease and metachronous
      lesions in the colorectum, this is less clear after oesophageal, gastric and
      pancreatic cancer surgery. Further studies are needed to establish what is the
      most effective follow-up protocol after different types of gastrointestinal
      cancer surgery.

PMID- 16627024
TI  - Familial Mediterranean fever in the Syrian population: gene mutation frequencies,
      carrier rates and phenotype-genotype correlation.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease
      mainly affecting particularly Arabs, Non-Ashkenazi Jews, Armenians, and Turks. It
      is an autoinflammatory periodic disorder characterized by febrile and painful
      attacks due to inflammation involving the serosal membranes in the abdomen, chest
      or joints. Over 50 mutations have been identified in the MEFV gene responsible
      for FMF. OBJECTIVE: To identify the distribution and the frequency of the MEFV
      gene mutations in Syrian FMF patients and population and perform a
      genotype/phenotype correlation in the patients' cohort. PATIENTS AND METHODS: The
      study was carried out on 83 clinically diagnosed Syrian FMF patients and 242
      healthy subjects. The tested individuals were screened for the most common five
      MEFV mutations (M694V, M694I, M680I, V726A and E148Q) by restriction fragment
      length polymorphism. Sequencing of exon 10 was performed only for the patients'
      DNA where just one or no mutation was detected. RESULTS AND DISCUSSION: Of the 83
      patients studied, 74 (89%) were positive either for one, two or three mutations
      and nine (11%) had no mutations detected. Of those positive for mutations, 25
      were homozygous, 30 were compound heterozygotes, three had complex alleles, and
      16 patients had only one mutation. The M694V, V726A, M694I, M680I and E148Q
      mutations accounted for 45.8%, 26%, 13.9%, 4.8% and 6% of the alleles,
      respectively. The carrier rate in the Syrian population for the tested mutations
      was 17.5%, E148Q being the most common mutation, followed by V726A and M694V. The
      severity of the disease and development of amyloidosis seem to have an
      association with M694V, the most common mutation in Syrian FMF patients.

PMID- 16627025
TI  - Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from
      their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs.
AB  - Bisphosphonates induce osteoclast apoptosis, thereby decreasing bone resorption
      and reducing the rate of bone remodeling. Earlier work from our group and others
      has demonstrated that, additionally, bisphosphonates prevent osteoblast and
      osteocyte apoptosis in vivo and in vitro, raising the possibility that perhaps
      part of their anti-fracture efficacy may result from preserving the integrity of
      the osteocyte network and prolonging the working time of bone forming cells.
      Whereas induction of osteoclast apoptosis results from inhibition of the
      mevalonate pathway or from conversion to toxic ATP analogs, prevention of
      osteoblastic cell apoptosis is mediated by connexin43 hemichannel opening and
      activation of the extracellular signal-regulated kinases (ERKs). We examined here
      the ability of several bisphosphonates, including novel analogs, to exert these
      two effects. All 16 bisphosphonates studied inhibited etoposide-induced apoptosis
      of MLO-Y4 osteocytic cells and osteoblastic cells derived from calvaria, with
      EC50 between 10(-12) and 10(-10) M. On the other hand, only 10 analogs induced
      apoptosis of RAW-264.7-cell-derived osteoclasts. Each of the 6 bisphosphonates
      that lack pro-apoptotic activity in osteoclasts but retain anti-apoptotic
      activity in osteoblasts and osteocytes has a structural-related analog that is
      active in both cell types. These findings indicate that the structural
      prerequisites for the anti-apoptotic effect of bisphosphonates on cells of the
      osteoblastic lineage are less stringent than the ones required to induce
      osteoclast apoptosis and confirm that bisphosphonates act on the two cell types
      by distinct mechanisms. Preservation of osteoblast and osteocyte viability
      without inducing osteoclast apoptosis by these bisphosphonates analogs opens new
      possibilities for the treatment of bone fragility in conditions in which a
      decrease in bone remodeling is not desirable.

PMID- 16627026
TI  - Raman spectroscopic evidence for octacalcium phosphate and other transient
      mineral species deposited during intramembranous mineralization.
AB  - To understand early mineralization events, we studied living murine calvarial
      tissue by Raman spectroscopy using fibroblast growth factor 2 (FGF2)-soaked
      porous beads. We detected increased levels of a transient phase resembling
      octacalcium phosphate in sutures undergoing premature suture closure.
      INTRODUCTION: Several calcium phosphates have been postulated as the earliest
      inorganic precursors to bone mineral. They are unstable and have not been
      previously detected in tissue specimens. Whether the same intermediates are
      formed in sutures undergoing premature closure is also unknown. METHODS: Six
      coronal suture tissue specimens from fetal day 18.5 B6CBA F1/J wild-type mice
      were studied. Three sutures specimens were treated with FGF2-soaked heparin
      acrylic beads to induce accelerated mineralization and premature suture closure.
      Three control specimens were treated with empty heparin acrylic beads. All
      sutures were maintained as organ cultures to permit repeated spectral analyses at
      12-24 h intervals over a 72-h period. RESULTS: During the first 24 h, the spectra
      contained bands of octacalcium phosphate (OCP) or an OCP-like mineral. The main
      phosphorus-oxygen stretch was at 955 cm(-1), instead of the 957-959 cm(-1) seen
      in bone mineral, and there was an additional band at 1010-1014 cm(-1), as
      expected for OCP. A broad band was found at 945 cm(-1), characteristic of a
      highly disordered or amorphous calcium phosphate. An increased amount of mineral
      was observed in FGF2-treated sutures, but no qualitative differences in Raman
      spectra were observed between experimental and control specimens. CONCLUSIONS:
      Inorganic mineral deposition proceeds through transient intermediates, including
      an OCP-like phase. Although this transient phase has been observed in purely
      inorganic model systems, this study is the first to report OCP or an OCP-like
      intermediate in living tissue. Raman microspectroscopy allows observation of this
      transient mineral and may allow observation of other precursors as well.

PMID- 16627027
TI  - Reproductive health risks in perspective.

PMID- 16627028
TI  - Surrogate markers, emboldened and boxed warnings, and an expanding culture of
      misinformation: evidence-based clinical science should guide FDA decision making
      about product labeling.

PMID- 16627029
TI  - WHO statement on hormonal contraception and bone health.

PMID- 16627030
TI  - Combined hormonal contraception and bone health: a systematic review.
AB  - This systematic review examined whether women who use combined hormonal
      contraception experience changes in risk of fracture or bone mineral density
      (BMD) that differ from nonusers. We identified 86 articles from PubMed and EMBASE
      (published 1966 to August 2005) that reported on fracture or BMD outcomes by use
      of combined hormonal contraceptives. The evidence relating to combined oral
      contraceptives (COCs) and fracture is inconclusive, as results from the available
      studies conflict. Studies of adolescent and young adult women generally found
      lower BMD among COC users than nonusers. Evidence for premenopausal adult women
      suggested no differences in BMD between COC users and nonusers. COC use in
      perimenopausal and postmenopausal women preserved bone mass, while nonusers lost
      BMD, but BMD among former COC users in this age group was the same as for never
      users. Evidence for other combined hormonal methods was very limited, with one
      study indicating no effect of combined hormonal injectable use among
      premenopausal women on BMD and one study suggesting lower BMD among premenopausal
      users of the NuvaRing than in nonusers.

PMID- 16627031
TI  - Progestogen-only contraception and bone mineral density: a systematic review.
AB  - Questions have been raised about the effects of progestogen-only contraceptive
      use on bone health, particularly among young women who have not yet reached peak
      bone mass and perimenopausal women who may be starting to lose bone mass. We
      conducted a systematic review that evaluated the association between progestogen
      only contraceptive use and fracture risk or bone mineral density (BMD). We
      identified 39 articles from MEDLINE and EMBASE, published through July 2005. One
      study reported that depot medroxyprogesterone acetate (DMPA) users were more
      likely to experience stress fractures than nonusers; this association was not
      statistically significant after controlling for baseline bone density. In cross
      sectional studies, the mean BMD in DMPA users was usually below that of nonusers,
      but within 1 SD. In longitudinal studies, BMD generally decreased more over time
      among DMPA users than among nonusers, but women gained BMD upon discontinuation
      of DMPA. Limited evidence suggested that use of progestogen-only contraceptives
      other than DMPA did not affect BMD.

PMID- 16627032
TI  - Acceptability and satisfaction using Quick Start with the contraceptive vaginal
      ring versus an oral contraceptive.
AB  - BACKGROUND: Many women discontinue their use of hormonal contraception, and even
      those who continue so may have difficulty using oral contraceptive pills
      consistently. New delivery systems, including the vaginal ring, may be easier to
      use, but user acceptability and satisfaction with these new methods may be
      affected by women's experience with their bodies. MATERIALS AND METHODS: Data for
      this study were collected as part of a randomized clinical trial on 201 women
      comparing immediate start of vaginal ring use with immediate start of low-dose
      oral contraceptive use. We assessed user satisfaction and method continuation 3
      months after ring or pill initiation. RESULTS: At 3 months, 174 of 201 subjects
      (87%) had follow-up interviews. Among the 174 study participants with follow-up
      data, 61% of ring subjects and 34% of pill subjects were very satisfied with
      their methods (p=.003). For posttrial contraception, 79% of ring subjects chose
      to continue with the ring whereas 59% of pill subjects chose to continue with the
      pill (p<.001). Women who reported greater comfort in touching their genitals,
      greater frequency of masturbation, more comfort with intercourse and past use of
      vaginal contraceptives and products were not more likely than others to be
      satisfied with the ring or to continue using it for birth control. CONCLUSION:
      Women who were allocated to vaginal ring use, regardless of their baseline
      characteristics or behavior, were likely to be highly satisfied with the method
      and to continue its use.

PMID- 16627033
TI  - Attitudes, perceptions and knowledge about the vagina: the International Vagina
      Dialogue Survey.
AB  - BACKGROUND: The International Vagina Dialogue Survey examined women's attitudes,
      perceptions and knowledge regarding the vagina. METHODS: In total, 9441 women (18
      44 years) from 13 countries underwent online interviews during April/May 2004.
      RESULTS: The majority of the women thought that vaginal health did not receive
      the attention it deserves (66%) and that society has too many misconceptions
      about the vagina (65%); indeed, 78% agreed that society's taboos surrounding the
      vagina contribute to women's ignorance. Only 39% of the women had ever read an
      informative article on the vagina, although 83% would like to read such an
      article. Although 79% of the women relied on advice from healthcare professionals
      (HCPs) when choosing a contraceptive, <50% were comfortable talking to HCPs about
      vagina-related issues. CONCLUSIONS: A more open and informative approach is
      needed with regard to the subject of the vagina in order to empower and educate
      women about their bodies and in matters such as choice of contraception.

PMID- 16627034
TI  - Agreement between women's and providers' assessment of hormonal contraceptive
      risk factors.
AB  - OBJECTIVE: To measure agreement between women's self-administered risk factor
      questionnaire and their providers' evaluation of their medical eligibility for
      hormonal contraceptive use. METHODS: This was an anonymous cross-sectional study.
      Participants were women 15-45 years old who completed a 20-item self-administered
      questionnaire. Women were recruited from six public health family planning
      clinics in the Seattle Metropolitan area. A matching medical evaluation
      questionnaire was completed concurrently by each participant's health care
      provider. Using provider evaluation as the "gold standard" against which we
      compared self-reported medical history, we calculated participant-provider
      agreement with point estimates and 95% confidence interval (CI). RESULTS: Of 399
      participant and provider pairs, participant-provider agreement was obtained for
      392 participant pairs. The majority of the participants (90.3%) were 15-30 years
      old and 77.7% had used a hormonal contraceptive method for more than 1 year. The
      estimated proportion of the overall agreement was 96% (95% CI, 0.92-0.98). Women
      were more likely to report severe headaches (12.4% vs. 3.3%), possible pregnancy
      (7.3% vs. 3.5%) and smoking (6.2% vs. 2.1%) than providers, but less likely to
      report smoking more than 15 cigarettes per day (2.6% vs. 9.2%) and irregular
      menses (6.5% vs. 9.9%). CONCLUSION: Overall, a high proportion of the women in
      this study completed our medical history questionnaire in concordance with their
      health care providers' same-day medical evaluation. Agreement on critical medical
      eligibility criteria such as hypertension was well above 90%. For criteria on
      which there was disagreement, women were more likely to identify
      contraindications than were their providers.

PMID- 16627035
TI  - Hormone levels before and after tubal sterilization.
AB  - OBJECTIVE: The aim of this study was to determine whether women experience
      significant luteal phase hormonal changes following interval tubal sterilization.
      DESIGN: This is a partly randomized, prospective clinical study. SETTING: This
      study involved healthy volunteers in an academic research environment. PATIENTS:
      This study involved 118 fertile women seeking tubal sterilization and 57 fertile
      controls with at least three normal cyclic menstrual periods before entry into
      the study. INTERVENTIONS: The patients were randomized to bipolar cautery or
      Hulka clip as sterilization methods. Barrier contraception or abstinence was used
      by controls. MAIN OUTCOME MEASURES: The main outcome measures are serum estradiol
      and progesterone levels and urinary estradiol and pregnanediol levels obtained
      during the luteal phase before, 1 year and 2 years after sterilization. RESULTS:
      The women randomized to the bipolar cautery group had higher midluteal
      progesterone levels measured between Days 5 and 11 postovulation (15.5 ng/mL
      before sterilization, 14.5 ng/mL at 1 year and 14.5 ng/mL at 2 years) than did
      the other two groups. The clip group had progesterone levels of 14.1, 12.0 and
      12.5 ng/mL at baseline, 1 year and 2 years, respectively, and the control group
      had levels of 12.0, 11.9 and 11.3 ng/mL for the same periods. Serum estradiol and
      progesterone and urinary pregnanediol and estradiol were not significantly
      changed over the 2-year period, nor were there significant differences between
      the two groups. CONCLUSIONS: There were no significant hormonal changes in
      sterilized women over a period of 2 years when compared with their baseline
      levels or when compared with unsterilized age-matched controls.

PMID- 16627036
TI  - Identifying women who will request sterilization reversal in a military
      population.
AB  - OBJECTIVE: We sought to identify the characteristics of women in a military
      population who are likely to seek a tubal anastomosis after a previous bilateral
      tubal ligation (BTL). METHOD: A written investigational review board-approved
      questionnaire was administered to 56 women, ages 18-40 years, requesting
      evaluation for a reversal of a prior BTL and 52 women of the same age range not
      seeking reversal. The questionnaire identified demographics and relationship
      characteristics of volunteers at the time of their decision to have a BTL and at
      the present time. RESULTS: Age 25 years or younger, sterilization due to pressure
      from a partner, poor marital relationship at the time of the BTL and a new
      marriage are highly predictive of tubal sterilization regret and a request for
      sterilization reversal in a military population. In addition, women requesting a
      tubal anastomosis reported less preoperative counseling on the permanence of a
      BTL and of the male alternative for permanent female sterilization, vasectomy.
      CONCLUSION: Women with these characteristics should have extensive counseling
      before undergoing tubal sterilization.

PMID- 16627037
TI  - Induction of second trimester abortion (12-20 weeks) with mifepristone and
      misoprostol: a review of 386 consecutive cases.
AB  - DESIGN: A retrospective analysis of 386 women who underwent termination of
      pregnancy between 12 and 24 weeks' gestation. METHODS: Each woman received 200 mg
      mifepristone orally followed by vaginal misoprostol 800 microg 36 to 48 h later.
      Three hours after the initial misoprostol administration, 400-microg doses of
      vaginal misoprostol were administered every 3 h, to a maximum of four doses in 24
      h. If abortion failed, 200 mg mifepristone is given again 3 h after the last
      misoprostol dose, followed by 12 h of rest before vaginal misoprostol
      administration is repeated as per previous course of treatment. RESULTS: Overall,
      97.9% and 99.5% of the women aborted within 24 and 36 h, respectively. The median
      induction-to-abortion interval was 6.7 h (range: 1.4-73.8 h), and nulliparous
      women took significantly longer time to abort (6.0 h in multiparous women
      compared to 7.6 h in nulliparous women; p<.0001). One woman failed to abort
      within 48 h. Surgical evacuation of the uterus was performed in 5% of women for
      incomplete abortion or retained placenta. Multiparous women were less likely to
      need analgesic administration for pain relief, and to experience vomiting and
      diarrhea, than nulliparous women. CONCLUSION: The combination of 200 mg
      mifepristone and vaginally administered misoprostol is a safe, effective and
      noninvasive regimen for termination of pregnancy between 12 and 20 weeks.

PMID- 16627038
TI  - Measuring pregnancy intention and its relationship with contraceptive use among
      women undergoing therapeutic abortion.
AB  - BACKGROUND: Most pregnancies ending in therapeutic abortion are assumed to have
      been unintended. In the developed world, most arise from inconsistent or
      incorrect contraceptive use. Ambivalence about pregnancy might be associated with
      less effective contraceptive use. METHODS: Three hundred sixteen women undergoing
      abortion in Scotland were interviewed about contraceptive use at the time of
      conception. A modified measure of pregnancy intendedness was used to determine
      ambivalence. RESULTS: Pregnancy appeared to be clearly unintended for 92% of
      women. Sixteen percent were not using contraception and had higher intendedness
      scores (p<.001) than those using a method. Forty-four percent were using
      contraception inconsistently or incorrectly, almost always condoms or oral
      contraception, but method choice was not linked to pregnancy intendedness.
      DISCUSSION: Women who are ambivalent about the desire for pregnancy are less
      likely to use contraception. The challenge for reducing abortion rates lies in
      improving contraceptive use among the much larger group of women who do not
      intend to get pregnant but use contraception imperfectly.

PMID- 16627039
TI  - Simultaneous very low dose mifepristone and vaginal misoprostol for medical
      abortion.
AB  - OBJECTIVE: This pilot study was designed to evaluate the outcome of medical
      abortion following simultaneous mifepristone (100 mg) and misoprostol (800
      microg). METHODS: Enrollees had gestational ages up to 56 days and desired a
      medical abortion. They received 100 mg of mifepristone orally and 800 microg of
      misoprostol vaginally. Follow-up examination occurred in 2-7 days. A phone call 3
      weeks later assessed symptoms and acceptability. A 95% success rate, as seen in
      higher dose studies, gives a 95% confidence interval of 88-100% for 40 subjects.
      RESULTS: Forty women were enrolled; 39 women had follow-up visits. Completed
      medical abortion was confirmed for 35 (90%) of 39 women. Four women had uterine
      aspiration. Two patients required repeat misoprostol. Median time from medication
      to abortion was 7 h. Most women (92%) strongly preferred taking all medications
      in the clinic. CONCLUSIONS: The simultaneous administration of vaginal
      misoprostol with 100 mg of oral mifepristone had the outcome of completed
      abortion within the predicted confidence interval. In addition, simultaneous
      dosing was highly acceptable.

PMID- 16627040
TI  - Effects of levonorgestrel-releasing intrauterine system on glucose and lipid
      metabolism: a 1-year follow-up study.
AB  - PURPOSE: This prospective study aimed to assess the possible effects of the
      levonorgestrel-releasing intrauterine system (LNG-IUS) on serum lipids and
      fasting blood glucose levels over a period of 1 year. METHODS: Forty-eight
      premenopausal women, attending our gynecology clinic with the complaint of
      menorrhagia, were enrolled in the study. Systolic and diastolic blood pressures
      were recorded. Serum concentrations of total cholesterol (TC), triglycerides
      (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein
      cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and fasting plasma glucose
      (FPG) levels were tested before (pretreatment group) and 1 year later following
      insertion (on-treatment group). Baseline mean parameters were compared with mean
      parameters at 1 year for statistical significance using paired samples t-test.
      RESULTS: Thirty-three (68.75%) women were eligible for control in the on
      treatment group. Mean age of the patients was 44.34+/-7.59 years. The study
      results showed that mean FPG level was significantly increased, whereas mean
      diastolic blood pressure was significantly decreased. Although mean systolic
      blood pressure tended to decrease and HDL-C concentrations to increase, these
      changes from baseline levels were insignificant. There were no significant
      changes in mean TG, TC, VLDL, LDL, AST and ALT. DISCUSSION: The only significant
      unfavorable effect observed was an increase in FPG level. Since it did not rise
      to risky values, but alerted us for the high risk patients for glucose
      intolerance before insertion. The LNG-IUS can be regarded as being safe in their
      effects on lipid metabolism, blood pressure and liver function tests.

PMID- 16627041
TI  - Ovarian cysts in users of Implanon and Jadelle subdermal contraceptive implants.
AB  - OBJECTIVE: To evaluate the prevalence of ovarian cysts in users of two
      contraceptive implants compared to users of intrauterine contraceptive (IUC).
      MATERIALS AND METHODS: A total of 344 women were enrolled at 3 months of use of
      the etonogestrel-releasing implant (Implanon), the levonorgestrel-releasing
      implant (Jadelle) or the TCu380A IUC. Bimanual pelvic examination and vaginal
      ultrasound were performed during routine 3-, 6- and 12-month visits of
      asymptomatic women. Women with ovarian cysts (or enlarged ovarian follicles > or
      = 25 mm) were assessed weekly until disappearance or reduction of the image
      [including estradiol (E2) and progesterone (P) measurement], and women with no
      ovarian enlargement underwent the same evaluation for the same period of time.
      RESULTS: Ovarian cysts were detected in 5.2%, 13.0% and 1.9% of users of
      Implanon, Jadelle and IUC, respectively, at 3 months. At 6 months of use,
      prevalence was 7.2%, 8.0% and 2.1%, whereas 12-month rates were 26.7%, 14.6% and
      1.2% in the three groups, respectively. E2 levels were significantly higher among
      users with ovarian cysts than controls. The time until disappearance of the
      ovarian cyst was similar in all three groups. There were more cases of
      menorrhagia in users of implants who had ovarian cysts than in those with no
      ovarian enlargement. CONCLUSIONS: The finding of ovarian cysts or enlarged
      ovarian follicles during the first year of use of Implanon and Jadelle implants
      is common and transient and should not be interpreted as a pathologic ovarian
      cyst. No further medical interventions are necessary.

PMID- 16627042
TI  - What is the desired menstrual frequency of women without menstruation-related
      symptoms?
AB  - INTRODUCTION: This study aimed to investigate the desired menstrual frequency of
      subjects without menstruation-related symptoms. MATERIALS AND METHODS: The study
      included 270 women of reproductive age. Women with menstrual headache,
      dysmenorrhea, hypermenorrhea and/or premenstrual syndrome were excluded. The
      study subjects completed a standardized questionnaire. RESULTS: Of the women,
      75.6% declared that menstrual periods interfere with their sexual life, 28.8%
      preferred not having their menstrual period when at work and 48.4% reported that
      menstrual periods interfere with practicing sports. Given the choice, 28.5% of
      the women would desire amenorrhea and 27.8% would prefer a reduction in the
      frequency of menstrual periods. Of the 152 women desiring to reduce menstrual
      frequency, 73.0% declared that they would accept to use a drug to reduce
      menstrual frequency. CONCLUSIONS: Over 50% of women without menstruation-related
      symptoms would like to lessen the frequency of menstrual periods and about 50% of
      them would desire amenorrhea.

PMID- 16627043
TI  - Vaginal safety after use of a bioadhesive, acid-buffering, microbicidal
      contraceptive gel (ACIDFORM) and a 2% nonoxynol-9 product.
AB  - BACKGROUND: ACIDFORM is a microbicidal and contraceptive candidate with strong
      buffering capacity. METHODS: This was a Phase I blinded, randomized and crossover
      clinical study on two products, ACIDFORM and a commercial nonoxynol-9 (N-9)
      product (2%), evaluating their vaginal safety in 20 couples aged between 19 and
      45 years. The women had regular menses, underwent previous tubal ligation, were
      not breast-feeding, had no vaginal sign and symptom and were in a stable
      partnership; both partners had no previous STI. Colposcopy, vaginal microbiology,
      inflammation markers and subject complaints were studied after coitus. Women were
      randomly assigned sequentially to receive ACIDFORM 0-30 min (0-30 min before
      intercourse), ACIDFORM 8-10 h (8-10 h before intercourse) or N-9 0-30 min after a
      control cycle. RESULTS: Mild/moderate vulvar irritation was observed in five
      postcoital test colposcopies, burning and pruritus were reported in six treated
      cycles and non-irritation-related symptoms were found in five cycles with
      different treatments. No difference in vaginal pH, Nugent scores, H2O2-producing
      lactobacillus or leukocytes and interleukin 6 in the cervicovaginal lavage was
      found between the treatment and control cycles. CONCLUSIONS: ACIDFORM appears to
      be safe for clinical use once a day. There is a potential spermicidal
      microbicidal role for ACIDFORM as a vaginal flora helper or as a vehicle for
      products, except N-9.

PMID- 16627044
TI  - The acceptability of an injectable, once-a-month male contraceptive in China.
AB  - PURPOSE: An acceptability study of an injectable preparation of the synthetic
      steroid testosterone undecanoate as a once-a-month male contraceptive method was
      carried out concurrently with, but independently from, a clinical safety and
      efficacy trial of this preparation in China, from 1997 to 1999. METHOD: Three
      hundred eight men, the entire group of volunteers enrolled in the clinical trial,
      were interviewed using a structured questionnaire. In addition, 24 sessions of
      focus group discussions and 54 in-depth interviews were conducted with a broad
      range of stakeholders, including men enrolled in the trial and their wives,
      potential users, service providers, principal investigators of the six
      participating clinical trial centers, provincial and national policy makers, and
      experts engaged in research and development of male methods of contraception.
      RESULTS: Overall, men found the regimen to be acceptable, and most reported no
      change or an improvement in their well-being as a result of participating in the
      clinical study. The frequency of the injections, monthly semen analyses and the
      need to use another contraceptive method during the period of sperm suppression
      were reported inconveniences of the trial. CONCLUSION: Further research is needed
      to assess the long-term safety, continuation rates, satisfaction among users and
      issues related to service delivery.

PMID- 16627045
TI  - Abortifacient effect of Prangos ferulacia on pregnant rats.
AB  - PURPOSE: Prangos ferulacea grows in southern Iran and used in Iranian herbal
      medicine for gastrointestinal disorders, but it seems it has an abortifacient
      effect on pregnant women. To verify its potential as an abortifacient agent, we
      administered the leaves of this plant to pregnant rats. MATERIAL AND METHODS:
      Hydroalcoholic and aqueous extract of the leaves was administered orally at
      different doses to 60 rats on the first 18 days of pregnancy. Group 1 (G1) was
      considered as control group and was given only water. Groups 2-5 (G2-G5) received
      25, 50, 100 mg/g per day and Groups 6-8 (G6-G8) received 300, 500 and 1000 mg/g
      per day, respectively. On Day 18 of pregnancy, they were killed and
      laparotomized. The uterine horns of each group were opened to see whether they
      contained any live and degenerated/dead fetuses. We used Student's t-test to
      analyze the data (p < or = .05 was considered significant). RESULTS: Of the total
      504 fetuses in the studied groups, 13 fetuses (2.57%) were aborted. The abortion
      rate in the control group was 2 (1.94%) of 103 fetuses; the abortion rate was
      higher in the treated groups but not statistically significant. There was no
      relationship between the dose and type of extract and abortion rate in all
      studied groups. CONCLUSION: This study shows that the aqueous or hydroalcoholic
      extract of P. ferulacea is ineffective on the rate of abortion of pregnant rats.
      Future studies should be performed with higher doses to test the efficacy of this
      agent on other animals.

PMID- 16627046
TI  - From JNC I to JNC 7--what have we learned?

PMID- 16627047
TI  - Clinical features in the management of selected hypertensive emergencies.
AB  - A hypertensive emergency is a clinical diagnosis that is appropriate when marked
      hypertension is associated with acute target-organ damage; in this setting,
      lowering of blood pressure (BP) is typically begun within hours of diagnosis. For
      hypertensive urgency with no acute target-organ damage, BP lowering may occur
      over hours to days. A hypertensive emergency may present with cardiac, renal,
      neurologic, hemorrhagic, or obstetric manifestations, but prompt recognition of
      the condition and institution of rapidly acting parenteral therapy to lower BP
      (typically in an intensive care unit) are widely recommended. For aortic
      dissection, the systolic BP target is lower than 120 mm Hg, to be achieved during
      the first 20 minutes using a beta-blocker (typically esmolol) and a vasodilator
      to reduce both shear stress on the aortic tear and the BP, respectively.
      Otherwise, sodium nitroprusside is the agent with the lowest acquisition cost and
      longest record of successful use in hypertensive emergencies; however, it is
      metabolized to toxic thiocyanate and cyanide. Other attractive agents include
      fenoldopam mesylate, nicardipine, and labetalol; in pregnant women, magnesium and
      nifedipine are used commonly. Most authors suggest a reduction in mean arterial
      pressure of approximately 10% during the first hour and a further 10% to 15%
      during the next 2 to 4 hours; hypoperfusion can result if the BP is lowered too
      suddenly or too far (eg, into the range of <140/90 mm Hg). Oral antihypertensive
      therapy can usually be instituted after 6 to 12 hours of parenteral therapy, and
      the patient moved out of the intensive care unit, when consideration should be
      given to screening for secondary causes of hypertension. Long-term follow-up to
      ensure adequate control of hypertension is necessary to prevent further target
      organ damage and recurrence of another hypertensive emergency.

PMID- 16627048
TI  - From left ventricular hypertrophy to congestive heart failure: management of
      hypertensive heart disease.
AB  - Other than age, left ventricular hypertrophy (LVH) is the most potent predictor
      of adverse cardiovascular outcomes in the hypertensive population, and is an
      independent risk factor for coronary heart disease, sudden death, heart failure
      and stroke. Although directly related to systolic blood pressure, other factors
      including age, sex, race, body mass index and stimulation of the renin
      angiotensin-aldosterone and sympathetic nervous systems play an important role in
      the pathogenesis of LVH. LVH involves changes in myocardial tissue architecture
      consisting of perivascular and myocardial fibrosis and medial thickening of
      intramyocardial coronary arteries, in addition to myocyte hypertrophy. The
      physiologic alterations which occur as a result of these anatomical changes
      include disturbances of myocardial blood flow, the development of an
      arrhythmogenic myocardial substrate and diastolic dysfunction. The latter is
      directly related to the degree of myocardial fibrosis and is the hemodynamic
      hallmark of hypertensive heart disease. When diastolic dysfunction is present,
      left ventricular end-diastolic pressure increases out-of-proportion to volume and
      may be elevated at rest or with exertion leading to clinical heart failure. At
      least one third of heart failure patients in the United States can be considered
      to have heart failure related to diastolic dysfunction. Compared to heart failure
      patients with systolic dysfunction, diastolic heart failure patients are more
      likely to be older, female, and to be hypertensive at the time of presentation.
      Although it has been assumed that LVH may lead to systolic dysfunction, evidence
      is lacking that LVH resulting from hypertension is a major risk factor for
      systolic heart failure independent of coronary artery disease. Treatment of
      hypertension greatly attenuates the development of LVH and significantly
      decreases the incidence of heart failure. In patients with established LVH,
      regression is both possible and desirable and results in a significant reduction
      in adverse clinical endpoints.

PMID- 16627049
TI  - Autonomic nervous system interaction with the cardiovascular system during
      exercise.
AB  - There is considerable recent evidence that parameters thought to reflect the
      complex interaction between the autonomic nervous system and the cardiovascular
      system during exercise testing can provide significant prognostic information.
      Specific variables of great importance include heart rate (HR) response to
      exercise (reserve), HR recovery after exercise, and multiple components of HR
      variability both at rest and with exercise. Poor HR response to exercise has been
      strongly associated with sudden cardiac death and HR recovery from a standard
      exercise test has been shown to be predictive of mortality. In addition, there
      are limited studies evaluating the components of HR variability at rest and
      during exercise and their prognostic significance. Research continues seeking to
      refine these exercise measurements and further define their prognostic value.
      Future findings should augment the power of the exercise test in risk-stratifying
      cardiovascular patients.

PMID- 16627050
TI  - Reducing infarct size in the setting of acute myocardial infarction.
AB  - Acute myocardial infarction is caused by coronary occlusion, and the mainstay of
      treatment has become reperfusion by either coronary angioplasty with possible
      stenting or surgical bypass grafting. Unfortunately, reperfusion can seldom be
      done soon enough to prevent infarction. Thus, the search for effective
      cardioprotection has been ongoing for more than 3 decades. After establishment of
      a suitable animal model to test the efficacy of pharmacological agents and other
      interventions, investigators found ischemic preconditioning to be a powerful and
      reproducible cardioprotectant. Much of the signaling pathway from cell receptor
      to end-effector has now been established even if the identity of the latter has
      not been proven. Remarkably, the actual protection is believed to occur during
      reperfusion rather than during ischemia. Yet, the clinical applicability of
      ischemic preconditioning is limited because of the obligate need to initiate it
      before ischemia. However, several strategies have been developed that can be
      applied at the time of reperfusion and which, therefore, hold clinical promise.
      These interventions are thought to trigger the same signaling cascades as
      ischemic preconditioning, which include activation of extracellular signal
      regulated kinase and phosphatidylinositol 3-kinase and also somehow prevent
      mitochondrial permeability transition pore formation. Ultimately, deployment of
      any of these strategies for clinical use must involve the pharmaceutical
      industry, which is becoming increasingly reluctant to be involved. Before any
      approach is tested in the clinical arena, however, it should be thoroughly vetted
      in preclinical settings. Only then can industry maximize the chances that its
      application in man will have the highest chance of success.

PMID- 16627051
TI  - Optimal medical therapy for heart failure.

PMID- 16627052
TI  - Operative trials: the opportunity beckons-an update on the American College of
      Surgeons Oncology Group.

PMID- 16627053
TI  - Advocacy by and for surgeons and our patients.

PMID- 16627054
TI  - Mississippi medical liability reform experience.

PMID- 16627055
TI  - Osler's advice to "shun politics" is outdated.

PMID- 16627056
TI  - A systematic review of reasons for nonentry of eligible patients into surgical
      randomized controlled trials.
AB  - BACKGROUND: The low recruitment rates into surgical randomized controlled trials
      (RCTs) threaten the validity of their findings. We reviewed the reasons for
      nonentry of eligible patients into surgical RCTs that would form the basis for
      future prospective research. METHODS: A systematic review of the English language
      literature for studies reporting reasons for nonentry of eligible patients into
      surgical RCTs and of recommendations made to improve the low recruitment rates.
      RESULTS: We reviewed 401 articles, including 94 articles presenting the results
      of 62 studies: 23 reports of recruitment into real surgical RCTs, 11 surveys of
      patients regarding hypothetical surgical RCTs, 10 surveys of clinicians and 18
      literature reviews. The most frequently reported patient-related reasons for
      nonentry into surgical RCTs were preference for one form of treatment, dislike of
      the idea of randomization, and the potential for increased demands. Distrust of
      clinicians caused by a struggle to understand, explicit refusal of a no-treatment
      (placebo) arm, and the mere inability to make a decision were frequently reported
      in studies of real RCTs and patient surveys, but were not emphasized in surveys
      of clinicians and review articles. Difficulties with informed consent, the
      complexity of study protocols, and the clinicians' loss of motivation
      attributable to lack of recognition were the most commonly reported clinician
      related reasons. CONCLUSIONS: There seems to be a discrepancy between real
      reasons for nonentry of eligible patients into surgical RCTS and those perceived
      by the clinicians, which require further prospective research. A summary and
      discussion of main recommendations sighted in the literature is presented.

PMID- 16627057
TI  - Operative indications for relatively small (2-5 cm) gastrointestinal stromal
      tumor of the stomach based on analysis of 60 operated cases.
AB  - BACKGROUND: Removal of the primary lesion with a clear operative margin is the
      standard treatment for gastrointestinal stromal tumor (GIST) of the stomach.
      However, there are few reports on the operative indications for relatively small
      GIST. METHODS: Clinicopathologic features and survival data of all 60 patients
      with GIST of the stomach treated at Keio University Hospital from 1993 to 2004
      were analyzed. Laparoscopic wedge resection was used as the primary procedure for
      tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or
      laparoscopy-assisted operation. RESULTS: Thirty-five lesions (58.3%) were
      resected by laparoscopic wedge resection, 3 by laparoscopic operation with a
      small skin incision and 22 by conventional open procedures. The mean size of the
      tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm.
      All operative margins were clear, but 1 patient had liver metastases at the time
      of resection of the primary lesion. The median follow-up period was 53 months and
      the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or
      distant metastasis was encountered in patients with tumors smaller than 4 cm. A
      statistically significant correlation was observed between tumor size and mitotic
      count in this cohort (P = .010). Tumors from the intermediate- (n = 14) and high
      risk (n = 10) groups as classified by the Risk Assessment Classification showed
      significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9%
      vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14
      cases (14.3%) were classified into the intermediate-risk group. CONCLUSIONS:
      Although a prospective randomized trial remains to be performed, this study
      provides additional evidence suggesting that the early removal of GIST, at 5 cm
      or less in size, provides better DFS than later removal of the tumor at a larger
      size.

PMID- 16627058
TI  - Motility of the pouch correlates with quality of life after total gastrectomy.
AB  - BACKGROUND: Jejunal pouch reconstruction is used to provide reservoir function
      after total gastrectomy, but controversy remains regarding pouch functions and
      quality of life (QOL). In this study, pouch motility was studied in conjunction
      with postoperative QOL. METHODS: Pouch motility of 23 patients with jejunal pouch
      interposition after total gastrectomy was examined by manometry under fasting
      conditions and by an emptying test using dual-scintigraphy under postprandial
      conditions. Residual food was graded by endoscopic examinations. QOL was
      evaluated using the Gastrointestinal Quality of Life Index, and a stasis- or
      dumping-related symptom score. RESULTS: The pouch showed interdigestive
      contractile activity. Bursts of contractile activity occurred frequently and were
      long-lasting compared with the migrating motor complex phase III of the control
      jejunum. The percentage of time of contractile bursts correlated with
      postprandial pouch emptying (liquid: R(2) = 0.229, P < .03; solid: R(2) = 0.243,
      P < .02). Patients with little or no residual food had more percentage of time of
      contractile bursts than those with moderate residual food (P < .01). The
      percentage of time of contractile bursts was correlated with the Gastrointestinal
      Quality of Life Index score (R(2) = 0.262, P < .02), stasis-related symptoms
      (R(2) = 0.279, P < .01), and dumping-related symptoms (R(2) = 0.218, P < .03).
      CONCLUSIONS: An interposed jejunum pouch showed bursts of contractile activity
      that affected postoperative gastrointestinal function and patient QOL.

PMID- 16627059
TI  - Individualized surgery for early gastric cancer guided by sentinel node biopsy.
AB  - BACKGROUND: We have reported that lymphatic mapping using indocyanine green (ICG)
      solution can be a good tool for identifying sentinel nodes (SNs) in gastric
      cancer. The purpose of this study was to evaluate individualized operations for
      gastric cancer guided by SN biopsy and to explore the possibility for more
      limited operative procedures using SN technology. METHODS: SNs were identified by
      using (99m)Tc-labeled tin colloid and ICG solution in patients with clinically
      T1N0M0 gastric cancer. When pathologic examination by frozen section revealed
      metastasis in SNs, we performed a standard D2 gastrectomy. Less extensive
      lymphadenectomy preserving vagus and pylorus was applied when the SN biopsy was
      negative. Then, postoperative pathology was analyzed. RESULTS: Among the 80
      enrolled patients, 7 patients with apparent node metastasis or T2-3 neoplasms and
      10 patients with positive metastasis in SNs underwent D2 gastrectomy. Sixty-one
      patients with negative metastasis in SNs underwent a less extensive, function
      preserving gastrectomy. The false-negative rate in sentinel node biopsy was 23%
      (3/13) for frozen section and 7% (1/14) for postoperative pathology. In 3
      patients with a false-negative result, metastasis was found in lymph nodes
      located at the station where the tracers were distributed. Of the 7 patients in
      whom metastasis was detected in 2 or more SNs by frozen section, postoperative
      pathology revealed that 3 patients (43%) belonged to the N2 category.
      CONCLUSIONS: SN biopsy is a useful tool for individualizing the operative
      procedure for early gastric cancer. Dissecting the lymph node stations only where
      the tracers are distributed may be a promising procedure for patients with no
      metastatic SNs.

PMID- 16627060
TI  - Mild hepatic steatosis is not a major risk factor for hepatectomy and
      regenerative power is not impaired.
AB  - BACKGROUND: An understanding of the regeneration power and operative risk of
      steatotic livers after hepatectomy is still unclear. We evaluated the volume
      regeneration and outcome of steatotic livers after donor hepatectomy. METHODS:
      Fifty-four, consecutive living liver donors from September 2002 to December 2003
      were evaluated prospectively by volumetric analysis, liver-spleen ratio, and
      liver attenuation index; the latter has been shown by serial computed tomographic
      scanning to be correlated strongly with histologic steatosis. Donors were
      followed up completely for at least 1 year (460-915 days) and were allocated
      according to histologic degree of macrovesicular steatosis: group 1, <5% (n =
      36); group 2, 5%-30% (n = 18). RESULTS: No mortality or hepatic failure was
      observed, and no donor required reoperation or intraoperative transfusion. The
      results of serial liver function tests, and major and minor morbidities were
      comparable between groups. Liver-spleen ratio and liver attenuation index
      remained at a constant level above normal values postoperatively in group 1, but
      increased rapidly above normal values in group 2. No difference in the rate of
      liver regeneration at 10 days after hepatectomy was found between the groups (P =
      .487), but the liver regeneration rate at 3 months after hepatectomy in group 1
      was slightly higher than that in group 2 (P < .044). However, no difference was
      observed between the 2 groups at 1 year after hepatectomy (P = .4). CONCLUSIONS:
      Mild hepatic steatosis is cleared immediately after hepatectomy, and early
      regeneration power is impaired, but the long-term regenerative power is
      comparable. Hepatectomy in donors with mild steatosis can be performed with low
      morbidity.

PMID- 16627061
TI  - Distribution of lymph node metastasis is a prognostic index in patients with
      stage III colon cancer.
AB  - BACKGROUND: In the TNM classification of colorectal carcinoma, N-staging is
      dependent on the number of metastases; in the Japanese classification system,
      staging usually has been based on the distribution of metastases (N1, paracolic;
      N2, along the major vessels; N3, at the root of major vessels). The aim of our
      study was to examine whether the concept of the distribution of nodal metastasis
      could improve the TNM classification for colorectal cancer. METHODS: We studied
      the survival rates of 485 and 136 patients with stage III colonic and rectal
      cancer, respectively, who underwent curative surgery between 1979 and 1998. The
      patients were categorized into 4 groups: group 1, TNM-N1 classified in J-N1;
      group 2, TNM-N2 in J-N1; group 3, TNM-N1 in J-N2-3; and group 4, TNM-N2 in J-N2
      3. RESULTS: In the colon cancer arm, the 5-year survival rates of the patients in
      groups 1 to 4 were 74%, 51%, 52%, and 54%, respectively. There was a significant
      difference in survival rate between groups 1 and 3 (P = .0002). Thus, in colon
      cancer, nodal metastasis along the major vessels was a bad prognostic factor,
      even though the number of nodes that were involved was <4. In the rectum cancer
      arm, the 5-year survival rates of the patients in each group were 65%, 39%, 60%,
      and 32%, respectively. Only the number of nodal metastases was an independently
      significant prognostic variable. CONCLUSION: This study suggests that adding the
      concept of nodal distribution to the conventional TNM staging of colon cancer
      will improve the accuracy in the evaluation of the nodal status.

PMID- 16627062
TI  - A United Kingdom survey of surgical technique and handling practice of inguinal
      canal structures during hernia surgery.
AB  - BACKGROUND: Recent trials have assessed the impact of elective nerve division on
      patient outcome after inguinal herniorrhaphy. The aim of this study was to
      establish UK surgical practice of handling of structures in the inguinal canal
      during herniorrhaphy. METHODS: A cross-sectional survey of all Fellows (n = 1113)
      of the Association of Surgeons of Great Britain and Ireland (ASGBI) was
      performed. The main outcomes were to determine method of inguinal hernia repair
      and routine practice for intra-operative handling of structures in the inguinal
      canal. RESULTS: A total of 852 (77%) questionnaires were returned, of which 784
      (92%) surgeons performed inguinal herniorrhaphy. Approximately two-thirds (63%)
      of responding surgeons performed less than 50 procedures per annum and 37%
      conducted more than 50 procedures annually. Mesh was the preferred method used by
      90% of surgeons; 6% used non-mesh, and 4% used other (laparoscopic) methods.
      Routine practice in relation to the inguinal structures varied by volume of
      hernia surgery; surgeons who conducted more than 50 procedures annually were more
      likely to visualize and preserve inguinal nerve structures. However,
      inconsistency in the answers suggested confusion over anatomy. CONCLUSION: This
      is the first UK survey to investigate method of hernia repair and usual handling
      practice of inguinal canal structures. There was wide acceptance of the use of
      mesh in inguinal hernia repair, with the majority of UK surgeons favoring an open
      approach. Surgeons performing high volumes of herniorrhaphy were more likely to
      preserve, rather than transect, inguinal nerve structures. This variation in
      practice may confound assessment of long-term neuralgia and other post
      herniorrhaphy pain syndromes.

PMID- 16627063
TI  - Indications for operative intervention in patients with asymptomatic primary
      hyperparathyroidism: practice patterns of endocrine surgery.
AB  - BACKGROUND: Currently, many patients with primary hyperparathyroidism (PHPT) are
      diagnosed when they are considered to be "asymptomatic." The need for
      parathyroidectomy in these patients has been questioned. A consensus statement
      drafted after the National Institutes of Health (NIH) 2002 Workshop on
      Asymptomatic PHPT provided guidelines for management of such patients but has
      been criticized for being too conservative. The purpose of this survey was to
      determine the impact of these guidelines on practice patterns of endocrine
      surgeons. METHODS: Members of the American Association of Endocrine Surgeons
      (AAES) were surveyed to determine whether previously published consensus
      guidelines for management of asymptomatic patients with PHPT are used to base the
      decision of whether to offer parathyroidectomy and to ascertain what parameters
      are considered indicators to proceed with operative intervention. AAES members
      were asked about the management of patients with asymptomatic PHPT, specialty
      characteristics, and demographics. RESULTS: Of 257 AAES members, 96 (37%)
      responded to the survey. Although the majority of the respondents were aware of
      and followed the NIH consensus conference guidelines, the majority of surgeons
      (80%) would operate on a patient with PHPT who did not meet these criteria but
      had other nonspecific symptoms. Surgeons favored operative intervention when
      preoperative localization studies were positive, even if the criteria of the NIH
      guidelines were not fulfilled. Most of the responders who would operate on all
      patients with PHPT, regardless of objective parameters, were surgeons with a high
      volume practice (>30 parathyroidectomies per year). The presence of multiple
      endocrine neoplasia (MEN) syndromes did not alter the decision to operate on
      asymptomatic patients. CONCLUSIONS: Endocrine surgeons do not base the decision
      to intervene operatively in patients with PHPT solely on objective criteria. Most
      high-volume, experienced endocrine surgeons believe that subjective complaints
      warrant operative intervention.

PMID- 16627064
TI  - Liver transplantation for primary and metastatic hepatic malignancy: a single
      center experience.

PMID- 16627065
TI  - The diurnal periodicity of hexose transporter mRNA and protein levels in the rat
      jejunum: role of vagal innervation.
AB  - BACKGROUND: Protein and messenger RNA (mRNA) levels of the hexose transporters
      sodium-dependent glucose transporter-1, glucose transporter 2, and glucose
      transporter 5 follow a (daily) diurnal rhythm in rat jejunum. Because vagal
      innervation mediates the diurnal activity of other proteins in the rat small
      bowel, we hypothesized that the diurnal variation of mRNA and protein levels of
      these hexose transport proteins are mediated by vagal innervation. METHODS: Forty
      eight rats kept in a strictly maintained, alternating 12-hour light-dark room
      underwent either sham laparotomy (n = 24) or bilateral total abdominal vagotomy
      (n = 24). Four weeks postoperatively, jejunal mucosa was harvested from 6 rats in
      each group at 3 am, 9 am, 3 pm and 9 pm; mRNA levels were determined by reverse
      transcription real-time polymerase chain reaction and protein levels by
      semiquantitative Western blot analysis. Transporter mRNA and protein levels were
      expressed as a ratio to the corresponding mRNA and protein levels of the stably
      expressed housekeeping gene glyceraldehyde-6-phosphate dehydrogenase. RESULTS:
      mRNA and protein levels for all 3 hexose transporters showed diurnal variation in
      sham controls (P < or = .01 for all). After vagotomy, although mRNA levels of all
      3 transporters showed diurnal variation (each P < .01), diurnal variation in all
      3 hexose transporter protein levels was abolished (P > .10 for all). CONCLUSIONS:
      Vagal innervation appears to differentially mediate the diurnal changes in hexose
      transporter mRNA and protein expression in the rat jejunum by
      posttranscriptional, and/or posttranslational processes.

PMID- 16627066
TI  - C3a levels and occurrence of subdermal vascular thrombosis are age-related in
      deep second-degree burn wounds.
AB  - BACKGROUND: After second-degree burns, thrombosis of the subdermal vascular
      plexus may occur, necessitating epifascial necrectomy instead of tangential
      excision to ensure split skin graft healing. Until now, no parameter has been
      obtained to explain this phenomenon. METHODS: Thirty-four patients with deep
      second-degree burn wounds were divided into 2 groups. In group 1, patients' age
      was < 60 years, in group 2, > 60 years. In each patient, 2 microdialysis
      catheters were introduced into subdermal tissue of deep second-degree thermal
      wounds immediately after admission. Another 2 catheters were introduced in
      control tissue. We measured biochemical parameters (lactate, glycerol and
      glucose) and complement 3a (C3a) until surgery was performed. The surgically
      removed tissue was examined histologically. RESULTS: In thermal wounds of both
      groups, glucose levels fell, but lactate and glycerol levels rose compared to
      healthy tissue. Within the first 24 hours after trauma, C3a levels were
      significant higher in both groups, compared with controls (P < .01). After 24
      hours the levels in group 1 had fallen to nonsignificant values, while in group 2
      these levels remained high until surgery was performed (P < .001). We found
      significantly more thrombotic blood vessels in deep dermal tissue of group 2 (P <
      .005). Abbreviated burn severity index score was comparable in both groups.
      CONCLUSIONS: C3a is continuously elevated in deep second-degree burned wounds in
      patients > 60 years. This finding may be related to the occurrence of
      significantly more thrombotic blood vessels in deep dermal tissue of elderly
      patients. Microdialysis therapy is a useful tool to measure metabolic and
      immunologic parameters in thermally damaged tissue.

PMID- 16627067
TI  - Long-term prognostic value of detection of circulating colorectal cancer cells
      using CGM2 reverse transcriptase-polymerase chain reaction assay.
AB  - BACKGROUND: The criteria commonly used for prognosis of colorectal cancer remain
      histoprognostic and are based on primarily TNM classification. The lack of
      discrimination of purely histoprognostic criteria is evidenced by the development
      of different outcomes in similarly staged patients. The aim of this work was to
      study the long-term prognostic value of preoperative detection of circulating
      enterocytes in the blood of colorectal cancer patients using the CGM2 reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: A nested RT-PCR
      with specific primers for CGM2 was used preoperatively to detect circulating
      enterocytes in 121 patients (64 men, 57 women; mean age, 70 years) with
      colorectal neoplasms. RESULTS: Circulating enterocytes were detected in 58/121
      (48%) patients. The positivity rate was not correlated with American Joint
      Committee on Cancer (AJCC) staging (stage I, 11/28 (39%); stage II, 13/34 (38%);
      stage III, 15/23 (65%); stage IV, 17/32 (53%); sterilized (after radiotherapy, no
      residual neoplasm) 2/4 (50%); not significant [NS]), but circulating enterocytes
      were detected more frequently in patients with metastatic lymph nodes (60% vs
      41%, P = .06). Overall 5-year survival rates (mean +/- SD) were 40 +/- 13% and 45
      +/- 13% for patients without and with circulating enterocytes, respectively (P =
      NS). Similarly, recurrence-free survival rates were 71 +/- 4% versus 72 +/- 14%
      (P = NS). Using univariate analysis, AJCC stage (P < .0001) was correlated with
      survival. AJCC stage (P = .007) and obstructive neoplasms (P = .043) were
      correlated with recurrence-free survival. Using multivariate analysis, AJCC stage
      was correlated with survival and recurrence-free survival. CONCLUSIONS:
      Preoperative detection of circulating enterocytes using CGM2 RT-PCR assay
      provides no specific prognostic information and cannot be used as a decision
      criterion for adjuvant therapy.

PMID- 16627068
TI  - Combination gene therapy of HGF and truncated type II TGF-beta receptor for rat
      liver cirrhosis after partial hepatectomy.
AB  - BACKGROUND: In a cirrhotic liver, the regenerative ability and specific functions
      are impaired; a hepatic resection increases the possibility of postoperative
      liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration,
      accelerates restoration of hepatic function, and improves fibrosis. A truncated
      type II transforming growth factor-beta receptor (TbetaTR), which specifically
      inhibits TGF-beta signaling as a dominant-negative receptor, appears to prevent
      the progression of liver fibrosis. We demonstrated the therapeutic efficacy of
      adenovirus-mediated HGF and TbetaTR gene transduction after partial hepatectomy
      for liver cirrhosis. METHODS: Rats were treated with dimethylnitrosamine for 3
      weeks, and they all had severe cirrhosis. After partial hepatectomy (10%), we
      injected adenovirus expressing bacterial beta-galactosidase (AdLacZ), adenovirus
      expressing a truncated type II TGF-beta receptor (AdTbetaTR), adenovirus
      expressing hepatocyte growth factor (AdHGF), or AdTbetaTR + AdHGF into the portal
      vein, which was followed by an additional 2-week dimethylnitrosamine treatment.
      RESULTS: On histologic examination, fibrotic tissue had decreased in the livers
      of the AdTbetaTR + AdHGF-treated rats compared with rats that were treated by
      AdLacZ, AdTbetaTR alone, and AdHGF alone. Liver function, which included serum
      levels of alanine aminotransferase, improved significantly in AdTbetaTR + AdHGF
      treated rats compared with all other groups. The number of hepatocytes that were
      positive for proliferating-cell nuclear antigen was greater (P < .05) in AdHGF
      alone and AdTbetaTR + AdHGF-treated rat livers than in AdLacZ- and AdTbetaTR
      treated rats. All AdTbetaTR + AdHGF-treated rats survived >60 days, and AdTbetaTR
      + AdHGF treatment markedly improved the survival rate after a partial
      hepatectomy. CONCLUSION: Our results suggest that the combination of HGF and
      TbetaTR gene therapy may increase the possibility of hepatectomy in a cirrhotic
      liver by improving fibrosis, hepatic function, and hepatocyte regeneration.

PMID- 16627069
TI  - Emergency department resuscitative thoracotomy for nontorso injuries.
AB  - BACKGROUND: Resuscitative thoracotomy performed in the emergency department (EDT)
      continues to have clear indications in patients sustaining trauma to the torso,
      particularly penetrating injuries. However, adjunctive use of aortic cross
      clamping during EDT for hemorrhagic shock also may be useful in the acute
      resuscitation of patient with nontorso injuries (NTI). We questioned the utility
      of EDT in patients with nontorso trauma. METHODS: Patients undergoing EDT have
      been prospectively followed since 1977 at our regional level I trauma center.
      RESULTS: During the 26-year study period, 959 patients underwent EDT; 27 (3%) of
      these patients underwent EDT for penetrating NTI. Three (11%) of these patients
      survived to leave the hospital, with only 1 patient sustaining mild neurologic
      deficit. The mechanism of injury in the survivors was stab wound to the neck (1),
      gunshot wound to the neck (1), and extremity vascular injury (1). All survivors
      of EDT for NTI underwent prehospital cardiopulmonary resuscitation and successful
      endotracheal intubation in the field. There were no survivors of EDT for
      penetrating injury to the head. CONCLUSIONS: Resuscitative EDT with aortic cross
      clamping is a potential adjunct in the acute resuscitation of NTI involving
      penetrating neck or extremity vascular injuries.

PMID- 16627070
TI  - Breast cancer metastatic to renal cell carcinoma.

PMID- 16627071
TI  - Ectopic thyroid in the adrenal gland presenting as cystic lesion.

PMID- 16627072
TI  - How to meta-analyze trials of perioperative beta blockade.

PMID- 16627075
TI  - The assessment of the older adult with a physical disability: a guide for
      clinicians.
AB  - As the population of older adults increases, so does the number of people aging
      with a disability. It is more important than ever that clinicians caring for
      these individuals ask appropriate questions and focus on key areas of the
      physical examination that are pertinent to the care of this population. This
      article is meant to provide clinicians with a framework for evaluating the older
      adult aging with a physical disability in a clinic or hospital setting.

PMID- 16627076
TI  - Exercise in the elderly: research and clinical practice.
AB  - Exercise programs for elderly patients have received much attention recently for
      their potential role in preventing illness and injury, limiting functional loss
      and disability, and alleviating the course and symptoms of existing cardiac,
      pulmonary, and metabolic disorders. The basic components of an exercise training
      program include strength, endurance, balance, and flexibility. This article
      reviews the main attributes of each, along with some of the most recent research
      defining their roles in health care. Where available, it discusses specific
      recommendations for prescribing exercise modalities. Finally, it presents
      suggestions for developing integrated exercise programs and enhancing patient
      compliance.

PMID- 16627077
TI  - Rehabilitation outcomes in the older adult.
AB  - Numerous studies support the use of rehabilitative interventions in the older
      adult. Given the many fiscal challenges in health care today, it is of utmost
      importance that funding for rehabilitation result in fruitful outcomes. Specific
      rehabilitative interventions have been found to be very effective in the elderly
      and can be demonstrated through numerous studies. Outcomes for conditions
      including stroke, traumatic brain injury, spinal cord injury, amputation, hip
      fracture, and joint replacement are discussed. There is great need for ongoing
      research to determine optimal rehabilitative interventions in the elderly.

PMID- 16627078
TI  - The role of the physical therapist in the care of the older adult.
AB  - Physical therapists play an important role in the care of older adults who have
      physical disabilities. Proper patient selection, a thorough medical, social, and
      functional history, and a physical examination emphasizing the
      neuromusculoskeletal system are the cornerstones of the evaluation process.
      Treatment is individualized and goal driven, with appropriate precautions being
      followed. Gait training is an integral part of the treatment process for many
      older adults with disabilities, and various assistive devices may be used to
      ensure safe mobility.

PMID- 16627079
TI  - The role of occupational therapy in the care of the older adult.
AB  - Older adults who have physical disabilities often require the services of an
      occupational therapist. This article reviews the role of the occupational
      therapist in the care of the geriatric population.

PMID- 16627080
TI  - Speech, language, and swallowing disorders in the older adult.
AB  - The geriatric population has become a major component in the practice of medical
      speech-language pathology. This article discusses normal and abnormal functions
      of speech, voicing, language, cognition, and swallowing. Particular attention is
      given to disorders affecting the geriatric population. Evaluation, treatment, and
      ethical issues are explored in addition to the role of the speech-language
      pathologist on the interdisciplinary team.

PMID- 16627081
TI  - Neurogenic bowel and bladder in the older adult.
AB  - Special skills are needed in caring for an elderly patient with a neurogenic
      bowel and bladder. One not only has to take into account the age-related changes
      that occur, but also how these changes impact on a patient already struggling
      with bowel and bladder issues because of various neurogenic causes. Incontinence
      of bowel and bladder leads to a loss of quality of life and physicians should be
      educated on the treatment available to provide the best care for their patients.

PMID- 16627082
TI  - A geriatrician's guide to the use of the physical modalities in the treatment of
      pain and dysfunction.
AB  - The use of the physical modalities in the treatment of musculoskeletal conditions
      has a long and rich history. This article explores the various physical
      modalities and their indications, precautions, and contraindications, especially
      in their applied use in pain management. It also highlights the role of the
      physical modalities as agents for the management of pain in the geriatric
      population.

PMID- 16627083
TI  - Wheelchair evaluation for the older adult.
AB  - This article focuses on basic principles of seating and wheelchair evaluation for
      the general population. The discussion includes wheelchair options, components,
      and accessories. Basic principles to guide the clinician in the process of
      selection for maximum function are addressed.

PMID- 16627084
TI  - Prosthetics and orthotics for the older adult with a physical disability.
AB  - Prosthetics and orthotics serve many functions for the elderly and disabled.
      Assessment of patients in need of such devices is discussed. Prosthetic and
      orthotic devices are described with attention to their components, biomechanical
      effects, and potential value to patients. Strategies for selecting the proper
      device are presented. Structured rehabilitation is vital to ensure that patients
      maximally benefit from these devices; strategies for optimizing a rehabilitation
      program are discussed.

PMID- 16627085
TI  - Balance in the elderly.
AB  - Balance dysfunction remains a significant contributing factor for disability in
      the elderly. A wide variety of surgical, pharmaceutical, medical, and
      rehabilitation treatment options exists for these patients. The complexity of the
      balance system, however, often requires a thorough, multidisciplinary approach to
      the evaluation and successful treatment of balance impairment.

PMID- 16627086
TI  - Principles of geriatric dentistry and their application to the older adult with a
      physical disability.
AB  - The older adult living with a physical disability faces many daily challenges.
      Limited hand function or impaired cognition often has profound effects on
      activities of daily life including oral hygiene. This article explores age
      related changed in dentition and common causes of pathology of the oral cavity
      with special emphasis in populations with impaired hand function or cognition.
      This article will also assist the treating physician as it relates to oral
      diagnosis and patient management.

PMID- 16627087
TI  - Rehabilitation of the older adult with an osteoporosis-related fracture.
AB  - Osteoporosis is the most common metabolic bone disease and is clinically silent
      until it manifests in the form of fracture. When this occurs, significant
      deformity and disability can result. Appropriate rehabilitation of fracture
      includes antiosteoporotic medication; exercise programs; fall prevention;
      orthoses, such as bracing and hip protectors; and the minimally invasive
      procedures vertebroplasty and kyphoplasty.

PMID- 16627088
TI  - Traumatic brain injury in the elderly: diagnostic and treatment challenges.
AB  - The purpose of this review is to introduce geriatric practitioners to issues and
      challenges presented in the elderly after onset of traumatic brain injury (TBI).
      Issues discussed include the magnitude of TBI in the elderly, mechanisms of
      onset, issues specific to both acute and rehabilitation care for the elderly with
      TBI, and specific physical and behavioral manifestations of TBI that may need to
      be addressed on an inpatient or outpatient basis. General guidelines are provided
      for the diagnosis and treatment of older individuals who have TBI, with specific
      clinical scenarios illustrating key points.

PMID- 16627089
TI  - Rehabilitation of the older adult with stroke.
AB  - Stroke is an increasing public health concern throughout the world as the leading
      cause of long-term disability. It is well known that there exist differences
      related to epidemiology, pathophysiology, comorbidity, and functional outcome of
      stroke patients with advanced age compared with the young. Factors that have been
      suggested to influence this disparity include age-related complications,
      availability of resources, lack of aggressive management, and possible diminished
      capacity for neuroplasticity. This article reviews the current medical and
      rehabilitative aspects of stroke and the possible disparities related to advanced
      age.

PMID- 16627090
TI  - Infiltrative intestinal disease.

PMID- 16627091
TI  - Intra-abdominal abscess and peritonitis in an Appaloosa gelding.

PMID- 16627092
TI  - Chronic diarrhea and weight loss in three horses.

PMID- 16627093
TI  - Fluphenazine-induced extrapyramidal side effects in a horse.

PMID- 16627094
TI  - Secondary renal tubular acidosis in a quarter horse gelding.

PMID- 16627095
TI  - Congenital renal dysplasia in a 7-month-old quarter horse colt.

PMID- 16627096
TI  - Fever of unknown origin secondary to occult pleuropneumonia.

PMID- 16627097
TI  - Actinobacillus pleuritis and peritonitis in a quarter horse mare.

PMID- 16627098
TI  - Actinobacillus peritonitis in a Warmblood gelding.

PMID- 16627100
TI  - Fluid therapy: a primer for students, technicians, and veterinarians in equine
      practice.

PMID- 16627101
TI  - Equine fluid therapy: problem set.

PMID- 16627102
TI  - Duodenal stricture in a foal.

PMID- 16627103
TI  - Neonatal diarrhea and septicemia in an American Miniature Horse.

PMID- 16627104
TI  - Chronic hyperproteinemia associated with a probable abdominal abscess in an
      Appaloosa stallion.

PMID- 16627105
TI  - Postpartum hemoperitoneum and septic peritonitis in a Thoroughbred mare.

PMID- 16627106
TI  - Acute diarrhea in the adult horse: case example and review.

PMID- 16627107
TI  - Malabsorptive maldigestive disorder with concurrent Salmonella in a 3-year-old
      quarter horse.

PMID- 16627108
TI  - Severe metabolic acidemia, hypoglycemia, and sepsis in a 3-week-old quarter horse
      foal.

PMID- 16627109
TI  - Cholelithiasis and hepatic fibrosis in a standardbred mare.

PMID- 16627110
TI  - Liver disease in a 9-year-old Arabian stallion.

PMID- 16627111
TI  - Clostridial myositis and collapse in a standardbred filly.

PMID- 16627112
TI  - Polysaccharide storage myopathy in a 4-year-old Holsteiner gelding.

PMID- 16627113
TI  - Excessive drowsiness secondary to recumbent sleep deprivation in two horses.

PMID- 16627114
TI  - Left otitis media/interna and right maxillary sinusitis in a Percheron mare.

PMID- 16627115
TI  - Equine herpes myeloencephalopathy in a 12-year-old American quarter horse.

PMID- 16627116
TI  - Perinatal asphyxia syndrome in a quarter horse foal.

PMID- 16627117
TI  - Unilateral pyelonephritis in a miniature horse colt.

PMID- 16627118
TI  - Polydipsia and polyuria in a weanling colt caused by nephrogenic diabetes
      insipidus.

PMID- 16627119
TI  - Type 1 renal tubular acidosis in a broodmare.

PMID- 16627120
TI  - Rhodococcus equi pneumonia in a foal.

PMID- 16627121
TI  - Pneumonia and pleuritis in a mare.

PMID- 16627122
TI  - Diaphragmatic hernia in a 19-year-old thoroughbred broodmare.

PMID- 16627123
TI  - Disparities in access to fresh produce in low-income neighborhoods in Los
      Angeles.
AB  - BACKGROUND: Access to fresh produce and other healthy foods differs between poor
      ethnic and wealthier non-ethnic neighborhoods. Given the need to improve access,
      emergency food organizations, such as food pantries, can provide assistance. Food
      pantry clients, many living in poor ethnic neighborhoods, are at highest risk for
      inadequate intake of fruits and vegetables as emergency food assistance often
      does not include a supply of fresh produce. This study examines the extent to
      which food pantry clients live within reasonable walking distance of stores
      carrying fresh produce, and it proposes a strategy to increase accessibility of
      produce to those clients. METHODS: Addresses for 3,985 food pantry clients
      residing in Pomona, California, in 2003 and 84 food stores categorized as selling
      a "variety of produce" or "limited produce" were geocoded using geographic
      information systems technology in 2004. A 0.8-km network buffer was used to
      measure access to stores. Cluster areas with high densities of food pantry
      clients, or hot spots, were determined. RESULTS: Forty-one percent of Pomona food
      pantry clients were within walking distance of a store with fresh produce. Eighty
      three percent were within walking distance of stores with limited produce, and
      13% were not within walking distance of either store type. Seventeen cluster
      areas of food pantry clients accounted for 48% of clients with no access to a
      produce store. CONCLUSIONS: Using individual-level data allowed for the
      identification of significant numbers of food pantry clients with limited access
      to stores carrying a variety of fresh produce. Identification of the location of
      high concentrations of food pantry clients provides a potential solution to
      increase fresh fruit and vegetable access via mobile produce trucks.

PMID- 16627124
TI  - Changes in incidence of diabetes in U.S. adults, 1997-2003.
AB  - BACKGROUND: The incidence of self-reported diagnosed diabetes may be increasing
      because of recent changes in the diagnostic criteria for diabetes, enhanced case
      detection, and a true increase in disease incidence. These factors may also be
      changing the characteristics of newly diagnosed cases. Therefore, we examined
      recent trends in the incidence of diagnosed diabetes, changes to the
      characteristics of incident cases, and factors associated with incidence.
      METHODS: First, National Health Interview Survey data for 1997 to 2003 were used
      to examine 7-year trends in the incidence of diagnosed diabetes among U.S. adults
      aged 18 to 79 years. Second, among 1997-1998 and 2002-2003 incident cases,
      differences in sociodemographic characteristics, risk factors, and indicators of
      health status were examined. Lastly, multivariate-adjusted incidence from
      multiple logistic regression of 2001-2003 survey data were derived. RESULTS: From
      1997 to 2003, the incidence of diagnosed diabetes increased 41% from 4.9 to 6.9
      per 1,000 population (p <0.01). Incidence increased among men and women, non
      Hispanic whites, persons with at least a high school education, nonsmokers,
      active and inactive persons, and among obese persons (p <0.05). Obesity was more
      prevalent (p <0.01) and physical limitation was less prevalent (p =0.03) in 2002
      2003 versus 1997-1998 incident cases. Multivariate-adjusted incidence increased
      with age and BMI category, and decreased with education level (p <0.05).
      CONCLUSIONS: Obesity was a major factor in the recent increase of newly diagnosed
      diabetes. Lifestyle interventions that reduce or prevent the prevalence of
      obesity among persons at risk for diabetes are needed to halt the increasing
      incidence of diabetes.

PMID- 16627125
TI  - Colorectal cancer screening differential costs for younger versus older
      Americans.
AB  - BACKGROUND: Colorectal cancer (CRC) incidence rises with age, and most CRC arises
      from adenomatous polyps. It was therefore hypothesized that increased use of CRC
      screening and polypectomy in younger persons might yield CRC-related savings
      later in life for payers such as Medicare. METHODS: Using a decision analytic
      Markov model, the impact of increased CRC screening uptake on healthcare payers
      for younger Americans versus payers for older Americans, such as Medicare, was
      projected. RESULTS: As screening uptake increased, CRC incidence and mortality
      decreased, and annual costs related to CRC care and testing increased for younger
      persons, but decreased for older persons. Compared with current screening uptake
      of 40%, screening 75% of the U.S. population aged 50 to 80 increased annual costs
      related to CRC care and testing from 3.6 billion US dollars to 5.0 billion US
      dollars for 50- to 64-year-olds, but decreased annual costs from 5.9 billion US
      dollars to 5.6 billion US dollars for those aged 65 years and older. Sensitivity
      analyses suggest that future costs for other diseases could offset CRC care
      savings in older Americans that are attributable to screening. However, even
      without net cost savings for any age group, screening remained relatively cost
      effective. CONCLUSIONS: Investments in screening and polypectomy in younger
      persons may decrease CRC-related costs, including screening and surveillance, for
      healthcare payers for older Americans, including Medicare. While these savings
      could potentially be offset by future health costs for other diseases, screening
      would still be cost-effective. Widespread CRC screening beginning at age 50 must
      remain a national priority.

PMID- 16627126
TI  - Physical activity in men and women with arthritis National Health Interview
      Survey, 2002.
AB  - BACKGROUND: Regular physical activity in persons with arthritis has been shown to
      decrease pain, improve function, and delay disability. This study estimates the
      national prevalence of leisure-time physical activity and identifies factors
      associated with physical inactivity in adults with arthritis. METHODS: Data from
      the 2002 National Health Interview Survey were analyzed in 2004-2005 to estimate
      the proportion of adults with arthritis meeting four physical activity
      recommendations put forward in Healthy People 2010 and one arthritis-specific
      recommendation established by a national expert panel in arthritis and physical
      activity. Multivariate logistic regression was used to evaluate the association
      between inactivity and sociodemographic factors, body mass index, functional
      limitations, social limitations, need for special equipment, frequent
      anxiety/depression, affected joint location, joint pain, physical activity
      counseling, and access to a fitness facility. RESULTS: Adults with arthritis were
      significantly less likely than adults without arthritis to engage in recommended
      levels of moderate or vigorous physical activity, and 37% of adults with
      arthritis were inactive. In both men and women with arthritis, inactivity was
      associated with older age, lower education, and having functional limitations;
      having access to a fitness facility was inversely associated with inactivity.
      Among women, inactivity was also associated with being Hispanic, non-Hispanic
      black, having frequent anxiety/depression or social limitations, needing special
      equipment, and not receiving physical activity counseling. Among men, inactivity
      was also associated with severe joint pain. CONCLUSIONS: Although physical
      activity is a recommended therapy for people with arthritis, levels among adults
      with arthritis are insufficient, and those with arthritis have worse activity
      profiles than their peers without arthritis. Efforts to promote physical activity
      should include expanding access to evidence-based interventions and recreational
      facilities/programs. The importance of physical activity counseling and
      associated pain management measures by healthcare providers should be emphasized.

PMID- 16627127
TI  - Decision making in prostate-specific antigen screening National Health Interview
      Survey, 2000.
AB  - BACKGROUND: The net benefits and harms of prostate cancer screening with the
      prostate-specific antigen (PSA) test are uncertain, and professional
      organizations recommend that physicians discuss these uncertainties with patients
      before initiating screening. Using a nationally representative sample of men
      reporting past PSA screening, we aimed to determine the extent to which screening
      was initiated by physicians and preceded by physician-patient discussions.
      METHODS: Cross-sectional analysis of data from the 2000 National Health Interview
      Survey; 2,676 men aged 40 and older underwent PSA screening and met study
      inclusion criteria. We analyzed the proportions of men for whom PSA screening was
      (1) was initiated by the physician versus the patient, and (2) preceded by
      discussions about the test's advantages and disadvantages. RESULTS: Overall, 74%
      (95% CI=71.8-76.0) of recipients reported that PSA screening was initiated by
      their physician, and the proportion increased with advancing age, declining
      health status, lack of family history of prostate cancer, presence of a usual
      source of medical care, and non-Hispanic ethnicity. Sixty-five percent (95%
      CI=63.1-67.1) of screening recipients reported prescreening discussions with
      their physicians. Discussions were more common with physician-initiated screening
      than with patient-initiated screening, and among patients reporting a usual
      source of medical care, non-blue-collar occupation, and black race. CONCLUSIONS:
      Among U.S. men receiving PSA screening, screening is usually initiated by
      physicians, frequently in men relatively less likely to benefit from it, and
      often without prior discussion of the test's advantages and disadvantages.
      Further examination of the PSA decision-making process among screened and
      unscreened men is warranted.

PMID- 16627128
TI  - Gender and age disparities for smoking-cessation treatment.
AB  - BACKGROUND: Physicians play a critical role in tobacco-dependence treatment,
      especially prescribing cessation medications. However, it is unclear whether
      efforts are meeting recommended standards. This study evaluates the frequency and
      predictors of tobacco-use identification, counseling for tobacco dependence, and
      the prescription of cessation medications in a nationally representative sample
      of physician-patient encounters. METHODS: More than 58,000 physician-patient
      ambulatory encounters from the National Ambulatory Medical Care Survey 2001 and
      2002 were analyzed in 2004-2005, including patient demographics, diagnoses,
      tobacco counseling, and prescriptions. RESULTS: Tobacco-use status was identified
      in 69% of patient encounters, with 16% of those encounters indicating current
      use. Tobacco counseling occurred in 22.5% of visits by tobacco users, and 2.4% of
      tobacco users were prescribed cessation medications. These rates are similar to
      previous analyses in 1991. Patient characteristics associated with being more
      likely to receive counseling include being a new patient (adjusted odds ratio
      [OR]=1.34, 95% confidence interval [CI]=1.00-1.77) and having a tobacco-caused
      diagnosis (OR=2.71, CI=1.95-3.78). Characteristics associated with a lower
      likelihood of receiving medication include female gender (OR=0.45, CI=0.22-0.90)
      and age 65 and above (OR=0.14, CI=0.03-0.63), while a tobacco-caused diagnosis
      (OR=3.91, CI=1.64-9.29) and patient prompting (OR=15.31, CI=3.36-69.8) were
      associated with higher likelihood of receiving medications. CONCLUSIONS: Despite
      increasing national attention, the identification of tobacco status, counseling
      rates, and the use of cessation medications by physicians are low and unchanged
      from 1991. Women and elderly tobacco users were much less likely to receive
      prescriptions for cessation medications, while patients requesting treatment and
      those with tobacco-caused diagnoses were more likely. Further educational and
      public health campaigns are needed to encourage the use of these effective
      medications, especially in women and the elderly.

PMID- 16627129
TI  - Influence of primary care practice and provider attributes on preventive service
      delivery.
AB  - BACKGROUND: While visits to the doctor's office are appropriate times to advise
      patients on health behaviors, these opportunities are often missed. Lapses in
      care quality are no longer attributed solely to individuals, but are also
      increasingly understood to be the result of organizational factors. This research
      examines the influence that both practice and provider attributes have on the
      delivery of preventive services for health behaviors. METHODS: This study used
      data collected from the Prescription for Health initiative sponsored by the
      Robert Wood Johnson Foundation. Quantitative data on 52 primary care practices
      and 318 healthcare providers were gathered from September 2003 to September 2004,
      and were analyzed upon completion of data collection. Hierarchical linear
      modeling was used to examine associations between both practice and provider
      attributes and preventive service delivery. RESULTS: Practice staff participation
      in decisions regarding quality improvement, practice change, and clinical
      operations positively influenced the effect of work relationships and negatively
      influenced the effect of practice size on service delivery. Nurse practitioners
      and allied health professionals reported more frequent delivery of services
      compared to physicians. Last, use of reminder systems and patient registries were
      positively associated with preventive service delivery. CONCLUSIONS: This study
      offers preliminary support for staff participation in practice decisions as a
      positive aspect of teamwork and collaboration. Findings also suggest leveraging
      nonphysician clinical staff and organized clinical systems to improve the
      delivery of preventive services for health behaviors.

PMID- 16627130
TI  - Unintentional prescription drug overdose deaths in New Mexico, 1994-2003.
AB  - BACKGROUND: New Mexico has the highest rate of drug-induced mortality in the
      United States. The contribution of prescription drugs to the total overdose death
      rate has not been adequately described. METHODS: A total of 1,906 unintentional
      drug overdose deaths occurring in 1994 to 2003 in New Mexico were analyzed.
      Unintentional drug overdose death was defined as death caused by prescription,
      illicit, or a combination of drugs, as determined by a pathologist. Deaths were
      investigated annually by the medical examiner and data were analyzed in 2004
      2005. Rates and trends of total and prescription drug overdose death were
      calculated, decedent characteristics were analyzed, and common drug combinations
      causing death were described. RESULTS: The rate of unintentional prescription
      drug overdose death increased by 179% (1.9 to 5.3/100,000) from 1994 to 2003. A
      high percentage of prescription drug overdose decedents were white non-Hispanic
      (63.2%) and female (43.9%). These decedents were older and less frequently had
      alcohol listed as an additional cause of death than decedents of other drug
      overdose categories. Of all deaths caused by prescription drug(s) (n =765), 590
      (77.1%) were caused by opioid painkillers, 263 (34.4%) by tranquilizers, and 196
      (25.6%) by antidepressants. CONCLUSIONS: The rate of prescription drug overdose
      death in New Mexico increased significantly over the 10-year study period.
      Comprehensive surveillance of drug overdose deaths is recommended to describe
      their occurrence in the context of both medical and diverted use of prescription
      drugs. Understanding decedent profiles and the potential risk factors for
      prescription drug overdose death is crucial for effective drug overdose
      prevention education among healthcare providers.

PMID- 16627131
TI  - Food taxation and pricing strategies to "thin out" the obesity epidemic.
AB  - This article highlights characteristics of two related yet distinct economic
      approaches to addressing the current obesity epidemic in the United States: the
      general taxation of soft drinks, snack foods, and/or fast foods, and the
      application of pricing incentives/disincentives on foods sold in schools and
      worksites. The article specifically focuses on the: (1) rationale for, (2)
      potential barriers and limitations to, and (3) possible unintended consequences
      of implementing these policy interventions at the state level. Novel empirical
      evidence showing strong positive associations between the presence of state-level
      taxation on soft drinks or snack foods between 1991 and 1998 and relative changes
      in obesity prevalence over the same time period is further presented. The article
      concludes by summarizing the similarities and dissimilarities of the two
      approaches, and by emphasizing some of the gaps and priorities regarding these
      strategies that should be addressed in future research and policies to best
      effect obesity prevention.

PMID- 16627132
TI  - Risks and benefits of seafood consumption.

PMID- 16627133
TI  - Risks and benefits of seafood consumption.

PMID- 16627134
TI  - Risks and benefits of seafood consumption.

PMID- 16627137
TI  - Malignant tumors at the site of total hip prosthesis. Analytic review of 46
      cases.
AB  - During the years 1974 to 2003, a total of 46 cases of malignant tumors at the
      site of total hip arthroplasty, 41 sarcomas, 4 lymphomas, and 1 epidermoid
      carcinoma, have been reported in the Western literature. Soft tissue sarcomas
      occurred in 31 and bone sarcomas in 10 cases. Malignant fibrous histiocytoma was
      the most common in 20 (65%) of all soft tissue sarcomas. The patients with
      malignant tumors had been operated on more often for secondary osteoarthritis and
      had more local complications than those in ordinary total hip arthroplasty
      series. Primary osteoarthritis was the indication in 63% and secondary
      osteoarthritis in 37% of the 38 reported cases. Tumor developed after 8 (17%)
      revisions. Deep infection complicated 4 (9%) of the cases. Four cases (9%) were
      preceded by a precondition for cancer, 2 postradiation necroses of the femoral
      head, 1 chronic sinus, and 1 Mafucci syndrome. Mean age of the patients at the
      time of first implantation was 59 years (range, 24-79 years). The mean latent
      period was 6 years (range, 0.5-20 years) from the first operation. Longer latency
      period did not correlate positively with the cancer risk. Sarcomas were highly
      aggressive. Of the 31 reported patients, 24 (77%) died within 1 year after the
      diagnosis. The number of reported sarcoma cases is low considering the total
      population behind the cases. In addition, one observed local sarcoma from Nordic
      cohorts was less than expected. Chronic, particle-induced inflammation around the
      prosthesis does not seem to increase the risk for carcinogenesis.

PMID- 16627138
TI  - Total hip arthroplasty in patients with renal failure: a comparison between
      transplant and dialysis patients.
AB  - This study analyzed the outcome of total hip arthroplasty (THA) from a single
      institution of patients with renal failure, including renal dialysis patients (9
      patients, 9 hips) and renal transplant patients (28 patients, 36 hips). There
      were 12 revisions and a 61% complication rate in the transplant group. In the
      dialysis group, 1 patient was revised, and there was a 33% complication rate.
      Transplant patients were younger, more active, and lived longer, but had higher
      cumulative rates of revision and complications with longer follow-up. Dialysis
      patients, in contrast, had a short survival but a lower rate of complications and
      revisions. These data differ from previous reports of acceptable outcomes with
      low complication rates of THA in transplant patients. Efforts to minimize
      complications in these patients are justified.

PMID- 16627139
TI  - Relationship between product demand, tibial polyethylene insert shelf age, and
      total knee arthroplasty survival: retrospective review of total knees of one
      design.
AB  - Shelf aging of gamma-irradiated-in-air polyethylene tibial components has been
      associated with increased articular surface wear and an elevated risk for
      revision. Nine hundred fifty cruciate-retaining inserts of one design were
      implanted between 1987 and 1996 (shelf age, 1.0 +/- 1.2 years). Less frequently
      used inserts (smallest/largest sizes, thicker thicknesses, supplemental articular
      constraint) had longer shelf ages (means ranged from 1.2 to 2.6 years). Survival
      analysis showed that shelf age (P < .01) and gamma-sterilization in air (P = .01)
      elevated the risk for revision. Surgeons must remain attentive to identify the
      shelf-aged gamma-irradiated-in-air polyethylene tibial component while following
      designs from the era when this sterilization method was used. Recognition is
      expedited by understanding how shelf life is related to product demand and can be
      of aid when diagnosing the painful knee.

PMID- 16627140
TI  - Total hip arthroplasty with the porous-coated anatomic hip prosthesis: results at
      11 to 18 years.
AB  - The authors had previously reported good results with apparent fixation of a
      series of porous-coated anatomic hips at 2 to 4 years. In a larger series of 133
      hips with porous-coated anatomic uncemented components, 91 hips in 82 patients
      were available for a follow-up of 11 years or greater. Although 3.1% of
      acetabular cups had migrated or had been revised at 2 to 4 years; at 11 to 18
      years, there was 37% lysis, 21.7% migration, and 32.3% revision. For the femur at
      2 to 4 years, there was 3.1% migration and 1.5% revision. At 11 to 18 years,
      there was 27.2% lysis (proximal only), 6.6% migration, and 3.2% revision.
      Survival analysis for migration or revision for the femoral was 94%, and for the
      acetabular component, 63%, deteriorating markedly after 10 years.

PMID- 16627141
TI  - Comparison of two hydroxyapatite-coated femoral stems: clinical, functional, and
      bone densitometry evaluation of patients randomized to a regular or modified
      hydroxyapatite-coated stem aimed at proximal fixation.
AB  - Clinical function, bone mineral density (BMD), and radiographs of 80 randomly
      allocated, hydroxyapatite-coated femoral stems of two differing lengths were
      studied for 2 years. The short stem was optimized for proximal fixation. The
      predictive value of bone densitometry was also studied. After 2 years,
      significantly more bone apposition and a higher BMD percentage were observed in
      Gruen zone 7 of the short stem. We conclude that stem design can be enhanced to
      achieve more proximal fixation. However, we found a higher incidence of pain with
      the short stem, indicating a trade-off between increased proximal fixation and
      diminished overall mechanical stability. No strong correlations between clinical
      function and radiographic evaluation of remodeling were found with BMD,
      suggesting that dual-energy x-ray absorptiometry has no predictive value for
      short-term clinical outcome.

PMID- 16627142
TI  - Surface cementation of stemmed tibial components in primary total knee
      arthroplasty: minimum 5-year follow-up.
AB  - Cement remains the "gold standard" for fixation in total knee arthroplasty.
      Between 1991 and 1998, 128 consecutive knees in 109 patients underwent primary
      cemented total knee arthroplasty using a surface cementation technique. The
      average follow-up was 95 (range, 63-155) months. Preoperative range of motion
      (ROM) averaged 5 degrees to 111 degrees which improved to 1 degrees to 116
      degrees postoperatively. Modified Hospital for special surgery score (HSS) scores
      improved from 61 (range, 47-76) to 97 (range, 81-100) and the corresponding Knee
      Society Scores from 122 (range, 94-152) to 195 (range, 162-200). No osteolytic
      lesions were found; however, 3 tibias had radiolucent lines which were
      asymptomatic, nonprogressive, and not associated with implant failure. The
      average depth of penetration of cement was 2.7 mm. One knee (1%) required
      revision surgery for femoral loosening, and 1 required revision of the
      polyethylene liner. The present cementation technique provides excellent durable
      results at midterm follow-up.

PMID- 16627143
TI  - Total knee arthroplasty in the elderly. Is there an age limit?
AB  - The goal of this study was to compare the results of the total knee arthroplasty
      (TKA) in 2 study groups only differing by age. We have analyzed 218 TKA cases
      (138 women and 80 men) with at least 2 years follow-up. Mean age was 70 years
      (SD, 7.38 years; range, 43 to 98 years). An age cutoff point at 75 years defined
      the 2 study groups: 167 cases younger than 75 years and 51 older. Results were
      evaluated using the Hospital for Special Surgery Score. Mean score was raised
      from 53.43 (SD, 9.186) preoperatively to 85.57 (SD, 10.763) in 2 years follow-up
      (P < .001). The final score did not show significant differences between both
      groups (86.11 for the younger group and 83.8 for the older group). Differences in
      pain on walking, pain at rest, walk, range of motion, climbing stairs, transfer,
      muscle strength, or instability were not found between the patients younger and
      older than 75 years. We did not find any differences in TKA, functional score, or
      pain between the 2 studied groups.

PMID- 16627144
TI  - Impaction allografting for massive femoral defects in revision hip arthroplasty
      using collared textured stems.
AB  - We present a prospective study of impaction grafting using collared textured
      stems in femurs with massive defects (defined as requiring >150 cm(3) of
      cancellous allograft). Eighteen hips were followed for a minimum of 2 years.
      Average Harris hip scores increased from 50 preoperatively to 83 at most recent
      follow-up. Seventeen hips were functioning well at the time of most recent follow
      up and exhibited no stem subsidence or aseptic loosening. One hip was associated
      with visible subsidence and required further revision. Single-photon emission
      computed tomography analyses performed at an average of 37 months indicated
      active graft reorganization in all cases studied. Impaction allografting with
      collared textured stems for massive defects demonstrates good intermediate-term
      clinical results and may be a useful alternative to allograft stem composites and
      megaprostheses.

PMID- 16627145
TI  - Femoral revision with a fluted, tapered, modular stem seventy patients followed
      for a mean of 3.9 years.
AB  - Fluted tapered revision femoral stems have been used successfully in Europe.
      Modularity makes these implants more versatile, but outcomes of modular designs
      have not been reported. We report a retrospective review of 70 such stems with a
      mean follow-up of 47 months. Combined metaphyseal/diaphyseal bone loss was
      present preoperatively in 36 (51%) of 70 hips. Three hips (4.3%) were re-revised
      or in need of re-revision, and worst-case survival was 87%. The mean
      postoperative patient-assessed Oxford Hip Score was 21.1. Restoration of proximal
      bone was noted in 56%. Complications included mean subsidence of 9.9 mm,
      dislocation in 7 (10%) of 70 hips, and fracture or cortical perforation in 17
      (24.2%) of 70. These results are equivalent to, or better than, reported results
      of other types of cementless revision femoral stems.

PMID- 16627146
TI  - The influence of ambient theater temperature on cement setting time.
AB  - We have prospectively recorded ambient operating theater temperature from 186
      total knee arthroplasties and the time taken for the cement to set at
      implantation. The majority of cases used Antibiotic Simplex cement (n = 131), and
      the rest, Simplex with tobramycin (n = 55). Set time was defined as when a no. 15
      scalpel could not indent the cement surface at either the femoral or tibial
      interface. There was a reasonable negative correlation between temperature and
      setting time (Antibiotic Simplex: Pearson correlation coefficient, R = -0.674;
      Simplex with tobramycin: R = -0.655). There was also a considerable variation of
      setting time at any given theater temperature. There is an inverse relationship
      between ambient theater temperature and the setting time for Simplex cement, and
      surgeons should be aware that the setting time can vary considerably. Their
      operative protocol should take this into account.

PMID- 16627147
TI  - Coagulation parameters after retransfusion of unwashed blood.
AB  - Postoperative blood salvage reduces the risk of allogenic transfusion in patients
      undergoing elective total joint arthroplasty. We measured the concentrations of
      coagulation parameters after autotransfusion of unwashed shed blood in 22
      patients having elective joint arthroplasty and compared them with patients
      without retransfusion. Twenty-two patients with a total hip or knee arthroplasty
      received a mean of 611.4 mL unwashed but filtered shed blood. No complications
      were observed during or after the reinfusion of salvaged blood. Levels of D-dimer
      and fibrinogen increased significantly over time after retransfusion (P < .0001).
      Comparison of the autotransfused group with the 25 patients without reinfused
      shed blood showed no significant difference in fibrinogen concentration between
      the 2 groups in the postoperative course but a significant difference with
      increased D-dimer concentrations in the autotransfused group (P < .001).

PMID- 16627148
TI  - Ten-year survivorship of rough-surfaced femoral stem with geometry similar to
      Charnley femoral stem.
AB  - The aim of this study is to review the 10-year results of 269 cemented total hip
      arthroplasties performed using the Harvard femoral stem with matte surface finish
      and Charnley stem-like geometry. This is a retrospective cross-sectional
      survivorship study. We retrospectively reviewed the results of 269 cemented total
      hip arthroplasties performed using the Harvard femoral stem in 257 patients
      (men/women 93:164, mean age 71.2 years) between 1990 and 1994. The median
      duration of follow-up for the surviving implants was 118 (range 60-129) months.
      Radiographs were reviewed to evaluate the type of osteoarthritis, cement mantle
      thickness, alignment of the components, presence of aseptic loosening, and
      radiolucent lines. Kaplan-Meier survival analysis and Cox proportional hazards
      analysis were performed to evaluate 10-year survival and the impact of various
      radiological parameters on the prosthesis survival respectively. Of the 248
      eligible patients (260 hips), 6 patients (7 hips) were lost to follow-up, and 67
      patients had died at the time of the study; 36 hips (35 patients) underwent
      revision surgery for aseptic failure (median duration 60 months, range 12-125
      months), and 11 hips were revised for septic failure (median duration 24 months,
      range 10-53 months from the index procedure). The femoral component was revised
      in all patients, whereas the acetabular component was revised in 27 patients. Ten
      year survival for the femoral and acetabular components using aseptic loosening
      (with and without revision surgery) as an end point was 77.5% (71.5%-83.5%) and
      91.1% (87.2%-95%), respectively. Cox regression analysis did not reveal a
      statistically significant (P > 0.05) effect of various radiological parameters on
      survival rate. Our results demonstrate that the matte surface finish femoral
      component (with geometry similar to Charnley femoral component) has less
      satisfactory long-term survival rate.

PMID- 16627149
TI  - Outcome assessment in the elderly after total hip arthroplasty.
AB  - An analysis of the Short-Form 36 (SF-36) and Oxford Hip questionnaires, were used
      to assess 2 randomized groups, by either mail or interview, at a minimum 10-year
      follow up after total hip arthroplasty. Ninety-nine patients (median age 77
      years) were reviewed at a median 11 years after total hip arthroplasty. There was
      a 91% response rate to participation in the study. There was no significant
      difference between the groups for missing values. The mode of administration did
      not affect the mean Oxford scores (P > .1), but significant differences were
      noted in SF-36 health scales Role Emotional and Role Physical (P = .01). Analysis
      of other demographic variables revealed unexpectedly that comorbidity affected
      the Pain score in the Oxford questionnaire (P = .002) and that age had no effect
      on scores obtained in either questionnaire (P > .05). The uses of both general
      health and disease-specific questionnaires complement each other in the
      assessment of such groups. The SF-36 and Oxford questionnaires give a more
      accurate reflection of health status when self-completed while accepting higher
      missing values in an elderly population.

PMID- 16627150
TI  - A proposed classification of supracondylar femur fractures above total knee
      arthroplasties.
AB  - A new classification system is proposed for supracondylar femur fractures above
      total knee arthroplasties based on fracture location relative to the femoral
      component. Radiographs of 28 cases were evaluated and classified according to the
      proposed system by 12 physicians: 3 trauma specialists, 3 adult reconstruction
      specialists, 3 musculoskeletal radiologists, and 3 orthopaedic residents. The
      same 12 physicians reevaluated the same 28 cases 3 months later. The mean
      reliability coefficient for all observers was 0.74 (substantial agreement). The
      coefficient for reproducibility after 3 months was 0.85 (almost perfect). The
      power of the study was 80%. The proposed classification system is easy to use and
      has good interobserver reliability among orthopaedic residents, orthopaedic
      attendings--trauma and reconstruction--and radiologists. Intraobserver
      reliability was also excellent at 3 months.

PMID- 16627151
TI  - Common misconceptions of normal hip joint relations on pelvic radiographs.
AB  - This study defines normal bilateral variations in offset and hip center location
      on pelvic radiographs. The relationship of the femoral head center to the tip of
      the greater trochanter and that of offset to medullary canal diameter are also
      defined. Measurements of the offset, hip center location, height of the tip of
      the greater trochanter from the femoral head center, and medullary canal diameter
      were carried out on 100 normal pelvic radiographs. The offset of one hip was
      found to predict that of the contralateral hip to within 4.62 mm with 95%
      confidence. Their hip center locations differed by 6.3 mm. The tip of the greater
      trochanter was, on average, 8 mm higher than the femoral head center. Although
      offset generally increased with an increase in medullary canal diameter, frequent
      discrepancies occurred in their relationship.

PMID- 16627152
TI  - Reliable acetabular cup orientation with a new gravity-assisted guidance system.
AB  - Acetabular cup orientation is a key factor determining hip stability, and
      standard mechanical guides have shown little help in improving alignment. An in
      vitro study was carried out to compare the accuracy and precision of a new
      gravity-assisted guidance system with a standard mechanical guide. Three hundred
      ten cups were impacted by 5 surgeons, and the final cup orientation was measured.
      With the new guide, the average error in anteversion was 0.4 degrees , compared
      with 10.4 degrees with the standard guide and 0.3 degrees and -4.7 degrees ,
      respectively, for abduction angles. The average time required for orienting the
      cups was similar for both guides. The accuracy and reproducibility obtained with
      the new guide were better (P < .0001). These good results would require a
      clinical validation.

PMID- 16627153
TI  - Computer-assisted patellofemoral arthroplasty: a mechanism for optimizing
      rotation.
AB  - We reviewed the early outcome of 4 primary Avon patellofemoral arthroplasties
      performed by a single surgeon in a 1-year period. All operations were performed
      to treat symptomatic osteoarthritis, which had failed conservative management.
      All 4 procedures were performed with intraoperative computer navigation to enable
      correct alignment of the prosthesis. The patients were assessed clinically using
      the Oxford knee score and Crosby and Insall score. Radiologically, they were
      assessed using plain radiographs and computed tomography long leg and dynamic
      axial alignment views of the prosthesis. All patients had excellent early
      clinical and radiological results proving intraoperative navigation produces
      safe, reliable, and reproducible implant position in patellofemoral arthroplasty.

PMID- 16627154
TI  - The effectiveness of sequential medial soft tissue release on coronal alignment
      in total knee arthroplasty: using a computer navigation model.
AB  - Soft tissue management is a major step in total knee arthroplasty. We aimed to
      analyze the relationship between sequential medial soft tissue release and the
      resulting change in the anteroposterior limb axis and the tibiofemoral gaps.
      Measurements were obtained using a CT-free navigation system (Ci navigation
      system, DePuy I-Orthopaedics, Munich, Germany). Concerning leg axis, each release
      step led to significant (P < .001) effects. The highest effect was seen for the 6
      cm release in extension and the release of medial collateral ligament in 90
      degrees flexion. The medial gap difference was significant for each release step
      except the 4-cm release in extension. The highest increase resulted when
      sacrificing the entire posterior cruciate ligament in extension and in 90 degrees
      flexion. Implementation of computer-assisted surgery allows this first navigation
      controlled study, elucidating the effect of soft tissue release in total knee
      arthroplasty.

PMID- 16627155
TI  - Treatment of periprosthetic femoral shaft nonunion.
AB  - The purpose of this study is to review the contemporary treatment of
      periprosthetic femoral shaft nonunions. Thirteen periprosthetic femoral shaft
      nonunions in 13 patients were reviewed retrospectively. The average follow-up was
      48.3 months. Five patients were treated with open reduction and internal
      fixation, 3 patients were treated with open reduction and internal fixation and
      prosthesis revision, and 5 were treated with partial femoral replacing
      prosthesis. Functional outcomes were assessed using a modified Harris hip score.
      Twelve of 13 nonunions were treated successfully as defined by either
      radiographic union or a well-functioning prosthesis. Four major complications, 2
      requiring reoperation, were noted. These included persistent nonunion,
      dislocation, and new periprosthetic fracture. Successful treatment of
      periprosthetic femoral shaft nonunion yielded excellent pain relief, improved
      function, and patient satisfaction. However, complication and reoperation rates
      remain high.

PMID- 16627156
TI  - Factors influencing the initial micromotion between polyethylene acetabular cups
      and titanium alloy shells.
AB  - Mechanical test factors affecting short-term rotational stability under combined
      torsional and compressive loading was assessed in modular press-fit acetabular
      components with 4 different locking mechanism designs, by measuring the
      micromotion of the liner-shell interface at either room (20 degrees C) or body
      temperature (37 degrees C) and with either a high (2,943 N) or low (490 N)
      compressive load. Liner-shell constructs whose short-term stability was
      statistically significantly affected by temperature exhibited more rotational
      stability at body temperature than at room temperature. Liner-shell constructs
      whose short-term stability was statistically significantly affected by the level
      of compressive load exhibited more rotational stability with high compressive
      loads than with low loads. Liner-shell constructs with different locking
      mechanism designs were influenced by temperature and compressive loads
      differently. It is recommended to consider including these factors in tests of
      acetabular component locking mechanisms.

PMID- 16627157
TI  - Wiring through cannulated screws for the fixation of greater trochanter in
      arthroplasties performed for peritrochanteric fractures.
AB  - Safe and rigid fixation of a fractured greater trochanter is often very difficult
      because of osteoporosis of the fragments. The authors propose a new technique
      using cannulated screws and wires passed through the screws to fix the greater
      trochanter in arthroplasties performed for peritrochanteric fractures.

PMID- 16627158
TI  - Femoral perforation complicating contemporary uncemented hip arthroplasty.
AB  - This case series reports on 4 patients in whom intraoperative penetration of the
      femoral cortex occurred and went unrecognized on routine postoperative
      radiographs. This case series highlights some important points. Femoral cortex
      penetration can and does occur with uncemented hip arthroplasty and is likely to
      occur when surgical exposure is difficult and inadequate (such as in patients
      with severe obesity) or some form of proximal femoral deformity exists (such as
      patients with achondroplasia). Extra diligence should be exercised to avoid this
      complication in the high-risk patients, and adequate 2-plain radiographs may need
      to be ordered intraoperatively if such complication is suspected.

PMID- 16627159
TI  - Sciatic nerve palsy due to hematoma after thrombolysis therapy for acute
      pulmonary embolism after total hip arthroplasty.
AB  - Sciatic nerve paralysis as a complication of bleeding due to hip surgery is a
      rare entity. The use of thrombolysis and full-dose heparin administration for the
      treatment of massive pulmonary embolism increase the risk for developing major
      bleeding. Prompt recognition and intervention in this condition are warranted. A
      case of sciatic nerve palsy due to expanding thigh hematoma as a complication of
      thrombolytic therapy for pulmonary embolism after total hip arthroplasty is
      presented with a literature review. Although rare, this complication should be
      promptly recognized and immediate decompression should take place because of the
      favorable results of the early treatment.

PMID- 16627160
TI  - Magnetic resonance imaging to evaluate osteolysis around total knee arthroplasty.
AB  - Wear-induced osteolysis remains a common problem after total knee arthroplasty
      and may be particularly difficult to detect clinically or radiographically around
      the femoral component. We describe the use of magnetic resonance imaging to
      identify particulate-induced osteolysis around the distal femur and proximal
      tibia in 2 patients with total knee arthroplasties. The extent of the osteolysis
      was not apparent from standard x-rays, and the information provided by the
      magnetic resonance imaging facilitated preoperative discussion with the patient
      as well as preoperative planning for the surgery.

PMID- 16627161
TI  - Analysis of 16 retrieved proximal cemented femoral stems.

PMID- 16627165
TI  - Board certification upon graduation in Canada.

PMID- 16627167
TI  - Deferred extraction option for Class II subdivision malocclusion.

PMID- 16627168
TI  - A glimpse into the future.

PMID- 16627169
TI  - Outcome assessment of Invisalign and traditional orthodontic treatment and
      subsequent commentaries.

PMID- 16627170
TI  - Current concepts in the biology of orthodontic tooth movement.
AB  - Adaptive biochemical response to applied orthodontic force is a highly
      sophisticated process. Many layers of networked reactions occur in and around
      periodontal ligament and alveolar bone cells that change mechanical force into
      molecular events (signal transduction) and orthodontic tooth movement (OTM).
      Osteoblasts and osteoclasts are sensitive environment-to-genome-to-environment
      communicators, capable of restoring system homeostasis disturbed by orthodontic
      mechanics. Five micro-environments are altered by orthodontic force:
      extracellular matrix, cell membrane, cytoskeleton, nuclear protein matrix, and
      genome. Gene activation (or suppression) is the point at which input becomes
      output, and further changes occur in all 5 environments. Hundreds of genes and
      thousands of proteins participate in OTM. Gene-directed protein synthesis,
      modification, and integration form the essence of all life processes, including
      OTM. Bone adaptation to orthodontic force depends on normal osteoblast and
      osteoclast genes that correctly express needed proteins at the right times and
      places. Cell membrane receptor-ligand docking is an important initiator of signal
      transduction and a discovery target for new bone-enhancing drugs. Despite
      progress in identification of regulatory molecules, the genetic mechanism of
      "orchestrated synthesis" between different cells, tissues, and systems remains
      largely unknown. Interpatient variation in mechanobiological response is most
      likely due to differences in periodontal ligament and bone cell populations,
      genomes, and protein expression patterns. Discovery of mutations in OTM
      associated genes of orthodontic patients, including those regulating osteoclast
      bone-matrix acidification, chloride channel function, and osteoblast-derived
      mineral and protein matrices, will permit gene therapy to restore normal matrix
      and protein synthesis and function. Achieving selectivity in targeting abnormal
      genes, cells, and tissues is a major obstacle to safe and effective clinical
      application of gene engineering and stem-cell mediated tissue growth. Orthodontic
      treatment is likely to evolve into a combination of mechanics and molecular
      genetic-cellular interventions: a change from shotgun to tightly focused
      communication with OTM cells.

PMID- 16627171
TI  - Cellular, molecular, and tissue-level reactions to orthodontic force.
AB  - Remodeling changes in paradental tissues are considered essential in effecting
      orthodontic tooth movement. The force-induced tissue strain produces local
      alterations in vascularity, as well as cellular and extracellular matrix
      reorganization, leading to the synthesis and release of various
      neurotransmitters, cytokines, growth factors, colony-stimulating factors, and
      metabolites of arachidonic acid. Recent research in the biological basis of tooth
      movement has provided detailed insight into molecular, cellular, and tissue-level
      reactions to orthodontic forces. Although many studies have been reported in the
      orthodontic and related scientific literature, a concise convergence of all data
      is still lacking. Such an amalgamation of the rapidly accumulating scientific
      information should help orthodontic clinicians and educators understand the
      biological processes that underlie the phenomenon of tooth movement with
      mechanics (removable, fixed, or functional appliances). This review aims to
      achieve this goal and is organized to include all major findings from the
      beginning of research in the biology of tooth movement. It highlights recent
      developments in cellular, molecular, tissue, and genetic reactions in response to
      orthodontic force application. It reviews briefly the processes of bone,
      periodontal ligament, and gingival remodeling in response to orthodontic force.
      This review also provides insight into the biological background of various
      deleterious effects of orthodontic forces.

PMID- 16627172
TI  - Morphology of the temporomandibular joint in subjects with Class II Division 2
      malocclusions.
AB  - INTRODUCTION: Temporomandibular joint (TMJ) morphology has not been studied
      adequately in subjects with various types of malocclusion, and it is not known if
      TMJ morphology and facial morphology are related. Such knowledge might assist in
      the establishment of biological treatment strategies, especially when the TMJ is
      the target of the treatment plan. The aim of this study was to explore the
      morphological characteristics of the TMJ in subjects with skeletal Class II
      Division 2 malocclusions. METHODS: The material consisted of corrected lateral
      tomograms of 94 joints in 47 subjects with Class II Division 2 malocclusions (age
      range, 8.3-42.8 years). The subjects were divided into 5 groups according to age.
      RESULTS: Intragroup comparisons showed statistically significant differences for
      condylar angle, condylar position, eminence height, eminence inclination, ramus
      height, and condylar-neck height. These differences were found mainly between the
      youngest and oldest groups. The Pearson correlation coefficient was greater than
      0.60 for eminence height and eminence inclination, eminence height and ramus
      inclination, eminence inclination and ramus inclination, fossa posterior-eminence
      midpoint and fossa posterior-eminence top, and fossa posterior-eminence midpoint
      and fossa posterior-fossa roof. Condylar shape was most often round, followed by
      oval, flattened, and triangular; fossa shape was most often oval, followed by
      triangular, trapezoidal, and round. CONCLUSIONS: The results suggest that (1)
      fossa morphology and condylar length attain their final sizes early; (2)
      articular eminence and ramus morphology (height, inclination) have great
      variability; (3) some joint components such as eminence height with eminence
      inclination, eminence height with ramus inclination, eminence inclination with
      ramus inclination, and fossa anteroposterior dimensions are highly correlated
      with each other; and (4) the most prevalent condylar and fossa anteroposterior
      shape is oval.

PMID- 16627173
TI  - Evaluation of internal derangement of the temporomandibular joint by panoramic
      radiographs compared with magnetic resonance imaging.
AB  - INTRODUCTION: Panoramic radiographs are routinely used in orthodontic diagnosis
      and treatment planning. It would be useful if these radiographs could also
      provide information about internal derangement (ID) of the temporomandibular
      joint (TMJ). METHODS: The sample consisted of 168 condyles in 84 women. They
      underwent panoramic radiography on 1 of 3 machines and bilateral magnetic
      resonance imaging of the TMJ on 1 machine. Six panoramic variables were analyzed
      by 2-factor ANOVA to evaluate differences in condylar morphology with respect to
      status of the TMJ ID and type of panoramic machine. RESULTS: Decreased condylar
      heights and distally inclined condyles were found in the patients with TMJ ID,
      irrespective of the type of panoramic machine used. The change became more severe
      as ID progressed to disk displacement without reduction. CONCLUSIONS: This study
      suggests that some panoramic variables can help the clinician identify patients
      with potential ID.

PMID- 16627174
TI  - Herbst appliance therapy and temporomandibular joint disc position: a prospective
      longitudinal magnetic resonance imaging study.
AB  - INTRODUCTION: The objective of this prospective study was to verify changes in
      the position of the temporomandibular joint (TMJ) disc by means of magnetic
      resonance images (MRIs) in adolescent patients treated with the Herbst appliance.
      METHODS: Twenty consecutive Class II Division 1 patients treated with Herbst
      appliances were selected for the study. MRIs were analyzed at 3 stages:
      immediately before Herbst treatment (T1), 8 to 10 weeks after appliance placement
      (T2), and at the end of the 12-month Herbst treatment, immediately after
      appliance removal (T3). RESULTS: Class I or overcorrected Class I dental-arch
      relationships were observed after Herbst therapy. The qualitative evaluation
      showed that each patient had the disc within normal limits at T1. At T2, a slight
      tendency toward disc retrusion because of mandibular advancement was observed,
      but, at T3, the disc returned to normal, similar to T1 values. By using a
      quantitative evaluation, parasagittal MRIs (central, medial, and lateral slices)
      of the TMJs showed that there was no change of disc position from T1 to T3,
      except in the central slice, which had a retrusive position of the articular disc
      at T3. CONCLUSIONS: During the 12-month period of Herbst appliance treatment,
      mild changes in the position of the disc occurred in patients whose articular
      discs were within normal limits at T1. These changes were within normal
      physiological limits when evaluated in the short term.

PMID- 16627175
TI  - Lateral cephalometric characteristics of malocclusion patients with
      temporomandibular joint disorder symptoms.
AB  - INTRODUCTION: There is much controversy about the relationship between
      temporomandibular joint (TMJ) disorders and the skeletal structures of the lower
      face. It is not clear whether the disharmony of the facial skeletal structure is
      caused by the TMJ disorder or vice versa. The aim of this study was to determine
      the relationship between craniofacial skeletal structures and TMJ disorders by
      using lateral cephalogram measurements to examine the characteristics of the
      facial profile of patients with TMJ disorders. METHODS: Of 111 patients over 18
      years of age from the Department of Orthodontics, Dental Hospital, Yonsei
      University, those showing symptoms of TMJ disorders were chosen as the
      experimental group (56 patients), and patients without TMJ disorders were chosen
      as the control group (55 patients). A lateral cephalogram of each subject was
      taken and traced to confirm the significance of the craniofacial measurements
      between the experimental group and the control group of Class I (mean ANB angle,
      2.89 degrees), Class II (mean ANB angle, 6.32 degrees), Class III (mean ANB
      angle, -2.02 degrees) patients, who were grouped according to ANB-angle
      difference. RESULTS: Each experimental subject with a TMJ disorder had a
      hyperdivergent facial profile, more lingual tilting of the maxillary incisors,
      and a steeper inclined occlusal plane. CONCLUSIONS: There was a significant
      correlation between the structure of the lower face and the temporomandibular
      disorder.

PMID- 16627176
TI  - Physical properties of root cementum: part 7. Extent of root resorption under
      areas of compression and tension.
AB  - INTRODUCTION: The aim of this article was to quantify the extent of root
      resorption in areas of compression or tension under light and heavy buccal
      tipping orthodontic forces. METHODS: The sample consisted of 36 premolars in 16
      patients. On 1 side, light (25 g) or heavy (225 g) buccal tipping orthodontic
      forces were activated for 28 days. The contralateral side in each patient served
      as the control (0 g). The teeth were extracted, disinfected, imaged under a
      scanning electron microscope, and analyzed with commercial stereo imaging
      computer software modified for this study. Buccal and lingual surfaces were
      divided into 3 equal regions: cervical, middle, and apical. The root surface
      areas of these regions were documented with straight-on images. Quantification of
      resorption craters by using volumetric analysis was performed from stereo images
      taken at +/-3 degrees. The degree of resorption was correlated to the amount of
      surface area under compression or tension. RESULTS AND CONCLUSIONS: The buccal
      cervical region had 8.16-fold more root resorption in the heavy-force group
      compared with the light-force group (P <.01). The other regions did not seem to
      have significant differences in the force levels. In the experimental teeth,
      there was more root resorption in the high-compression regions than in the other
      regions (P <.01). There were similar amounts of resorption per unit area on the
      lingual apical and buccal cervical regions. Regions under compression had more
      root resorption than regions under tension. There was more resorption in regions
      under heavy compression than in regions under light compression (P <.01). There
      was also more root resorption in regions under heavy tension than in regions
      under light tension (P <.01).

PMID- 16627177
TI  - Palatal displacement of canines and maxillary skeletal width.
AB  - INTRODUCTION: The purpose of this study was to determine whether a clinically
      significant association exists between maxillary skeletal width and palatal
      canine impaction, also known as palatally displaced canine (PDC). METHODS:
      Seventy-nine patients with PDC were matched for age, sex, and malocclusion to 79
      controls. Maxillary and mandibular skeletal widths and nasal cavity widths were
      measured on posteroanterior cephalograms; maxillary and mandibular intermolar
      widths were measured on dental casts; and maxillary interalveolar arch widths at
      3 levels (canine, premolar, and first molar) were measured on occlusograms.
      RESULTS: Only maxillary alveolar arch width at the canine level was significantly
      different between the 2 groups. However, further analysis showed that the
      presence of erupted deciduous or permanent canines, rather than their absence in
      the canine area (whether due to extraction, exfoliation, impaction, or not yet
      having erupted), was strongly associated with maxillary intercanine alveolar arch
      width. CONCLUSIONS: The additional finding in this study that the eruptive status
      of canines significantly affects maxillary alveolar arch width in this area
      suggests that maxillary intercanine alveolar arch width as measured in this or
      other studies is not a good predictor of PDC.

PMID- 16627178
TI  - Dentoalveolar and skeletal changes associated with the pendulum appliance
      followed by fixed orthodontic treatment.
AB  - INTRODUCTION: This prospective clinical study analyzed the distalization of
      maxillary molars achieved by the pendulum appliance and its effect on the
      anchorage teeth during and after fixed orthodontic treatment. METHODS: Lateral
      cephalograms of 22 adolescents (15 girls, 7 boys) taken pretreatment, after
      distalization, after leveling and aligning, and after fixed orthodontic treatment
      were evaluated. The initial mean age was 14.5 years (SD = 1.80). The mean time
      for distalization of the maxillary molars was 5.85 months (SD = 1.82), and the
      total treatment time was 3.61 years (SD = 1.83). RESULTS: The pendulum appliance
      moved the maxillary molars distally, but with significant distal inclination,
      protrusion of the anterior teeth, and increase in lower anterior facial height
      (LAFH) due to the clockwise mandibular rotation. After fixed orthodontic
      treatment, the maxillary incisors and the maxillary first premolars and first
      molars were returned to their pretreatment anteroposterior positions. Thus, at
      postdistalization, there was 2.1 mm of protrusion of the maxillary first molars,
      despite the anchorage reinforcement (Nance button and cervical headgear worn at
      night during fixed appliance therapy). However, at the end of treatment, all
      patients had Class I molar relationships. CONCLUSIONS: The pendulum appliance
      followed by fixed orthodontic treatment corrected the Class II sagittal
      relationship, especially due to the dentoalveolar changes secondary to the
      spontaneous mandibular growth in the anterior direction during fixed appliance
      treatment.

PMID- 16627179
TI  - A comparison of dental arch forms between Class II Division 1 and normal
      occlusion assessed by euclidean distance matrix analysis.
AB  - INTRODUCTION: The purpose of the study was to use euclidean distance matrix
      analysis to compare dental arch forms between subjects with Class II Division 1
      malocclusions and normal occlusions. METHODS: The sample consisted of 60 subjects
      with Class II Division 1 malocclusions and 60 subjects with normal occlusions,
      all between 13 and 17 years of age. Fourteen landmarks, corresponding to cusp
      tips and incisor edges, were identified on the dental casts with a 3-dimensional
      measuring machine. All possible linear distances between pairs of landmarks in an
      arch were computed, and arch-form differences between Class II Division 1 and
      normal-occlusion subjects were tested by euclidean distance matrix analysis.
      RESULTS: In both sexes, the maxillary arches of the Class II Division 1 subjects
      were larger than the arches of the normal-occlusion subjects (1.8% and 2.7%
      larger for girls and boys, respectively), and arch shape was also significantly
      different (P < .001). The posterior teeth contributed to the shape difference
      between 2 groups more than the anterior teeth, moreover the main factor was
      narrow maxillary posterior arch width in the Class II Division 1 subjects. The
      mandibular arches of the Class II Division 1 subjects were also slightly larger,
      and arch shape was not significantly different regardless of sex. CONCLUSIONS:
      Expanding the maxillary posterior arch width in Class II Division 1 subjects
      might be an important method to harmonize maxillary and mandibular arch forms.

PMID- 16627180
TI  - The child perception questionnaire is valid for malocclusions in the United
      Kingdom.
AB  - INTRODUCTION: The purpose of this study was to validate the child perception
      questionnaire (CPQ(11-14)) with a sample of schoolchildren in Greater Manchester,
      United Kingdom. METHODS: We made a longitudinal survey of children from 1999 to
      2002, using the index of orthodontic treatment need (IOTN) at baseline when the
      children were 11 to 12 years old, the CPQ(11-14), and their uptake of orthodontic
      treatment 3 years later. RESULTS: CPQ(11-14) scores corresponded to differences
      in IOTN scores. These were related to the child's emotional and social well
      being. Regression analysis showed that CPQ(11-14) scores were higher for girls,
      for higher grades of the dental health component of the IOTN, and for children
      who thought that their teeth needed straightening. CONCLUSIONS: CPQ(11-14) has
      acceptable reliability and validity, and is likely to be a useful measure for
      orthodontic trials. The impact of malocclusion on a child's quality of life might
      be substantial.

PMID- 16627181
TI  - Effect of light-tip distance on the shear bond strengths of resin-modified glass
      ionomer cured with high-intensity halogen, light-emitting diode, and plasma arc
      lights.
AB  - INTRODUCTION: The purpose of this study was to assess the effect of light-tip
      distance on the shear bond strength and the failure site of brackets cured with 3
      light-curing units (high-intensity halogen, light-emitting diode, and plasma
      arc). METHODS: One hundred thirty-five bovine mandibular permanent incisors were
      randomly allocated to 9 groups of 15 specimens each. Stainless steel brackets
      (Victory Series, Unitek/3M, Monrovia, Calif) were bonded with a resin-modified
      glass-ionomer (Fuji Ortho LC, GC Europe, Leuven, Belgium) to the teeth, and each
      curing light was tested at 3 distances from the bracket: 0, 3, and 6 mm. After
      bonding, all samples were stored in distilled water at room temperature for 24
      hours and subsequently tested for shear bond strength. RESULTS: When the 3 light
      curing units were compared at a light-tip distance of 0mm, they showed no
      significantly different shear bond strengths. At a light-tip distance of 3 mm, no
      significant differences were found between the halogen and plasma arc lights, but
      both lights showed significantly higher shear bond strengths than the light
      emitting diode light. At a light-tip distance of 6 mm, no significant differences
      were found between the halogen and light-emitting diode lights, but both showed
      significantly lower bond strengths than the plasma arc light. When the effect of
      the light-tip distance on each light-curing unit was evaluated, the halogen and
      light-emitting diode lights showed no significant differences among the 3
      distances. However, the plasma arc light produced significantly higher shear bond
      strengths at a greater light-tip distance. No significant differences were found
      among the adhesive remnant index scores of the various groups, except with the
      LED light at a distance of 3 mm. CONCLUSIONS: In hard-to-reach areas, the plasma
      arc curing light is suggested for optimal curing efficiency.

PMID- 16627182
TI  - Shear bond strength of orthodontic brackets with 3 self-etch adhesives.
AB  - INTRODUCTION: The purpose of this study was to compare shear bond strength and
      mode of failure of brackets bonded with 3 self-etching products. METHODS: The
      products tested were (1) a recently developed, modified self-etching, 1-step
      adhesive system (Adper Prompt L-Pop Self Etch Adhesive, 3M, St Paul, Minn); (2) a
      new fluoride-releasing, antibacterial, self-etching adhesive system (Clearfil
      Protect Bond, Kuraray, Osaka, Japan); and (3) a fluoride-releasing, self-etching
      adhesive system (Transbond Plus Self Etching Primer, 3M). Thirty-six defect-free
      premolars were randomly divided into 3 groups (n = 12 each), and metal brackets
      were bonded according to the manufacturer's instructions. Brackets were debonded
      in shear on a universal testing machine with a crosshead speed of 1 mm per
      minute. RESULTS: One-way ANOVA showed a statistically significant (P < .001)
      difference between groups. Group 2 had the highest shear bond strength. The
      difference between groups 1 and 3 was not statistically significant. The Kruskal
      Wallis test showed no significant differences in the ARI scores (P = .595; P <
      .05). CONCLUSIONS: The fluoride-releasing, antibacterial, self-etching adhesive
      system, Clearfil Protect Bond, produced greater shear bond strength than the
      other 2 products tested and could be considered for clinical use.

PMID- 16627183
TI  - Comparison and measurement of the amount of anchorage loss of the molars with and
      without the use of implant anchorage during canine retraction.
AB  - INTRODUCTION: The purpose of this study was to compare and measure the amount of
      anchorage loss with titanium microimplants and conventional molar anchorage
      during canine retraction. METHODS: Subjects for this study comprised 10
      orthodontic patients (7 women, 3 men) with a mean age of 19.6 years (range, 18 to
      25 years), who had therapeutic extraction of all first premolars. After leveling
      and aligning, titanium microimplants 1.3 mm in diameter and 9 mm in length were
      placed between the roots of the second premolars and the first molars. Implants
      were placed in the maxillary and mandibular arches on 1 side in 8 patients and in
      the maxilla only in 2 patients. A brass wire guide and an intraoral periapical
      radiograph were used to determine the implant positions. After 15 days, the
      implants and the molars were loaded with closed-coil springs for canine
      retraction. Lateral cephalograms were taken before and after retraction, and the
      tracings were superimposed to assess anchorage loss. The amount of molar
      anchorage loss was measured from pterygoid vertical in the maxilla and sella
      nasion perpendicular in the mandible. RESULTS: Mean anchorage losses were 1.60 mm
      in the maxilla and 1.70 mm in the mandible on the molar anchorage side; no
      anchorage loss occurred on the implant side. CONCLUSIONS: Titanium microimplants
      can function as simple and efficient anchors for canine retraction when maximum
      anchorage is desired.

PMID- 16627184
TI  - Effects of endothelin antagonist tezosentan on orthodontic tooth movement in
      rats.
AB  - INTRODUCTION: Endothelin is a cytokine peptide present in the periodontal
      ligament in physiological conditions. Its concentration in the periodontal
      ligament doubles after 3 hours of axial loading of a tooth. The role of
      endothelin in orthodontic tooth movement has not yet been explained. We tried to
      determine the effect of tezosentan, a specific dual endothelin receptor
      antagonist, on orthodontic tooth movement in rats. METHODS: Twenty-one rats were
      divided into 3 groups (n = 7). In the tezosentan group, closed-coil springs were
      placed, and the animals were treated daily with tezosentan; in the coil-spring
      group, closed-coil springs were placed, and the animals were treated with an
      inert physiological solution. The appliance was placed between the maxillary left
      first molar and the incisor. The third group was the control group. On days 0, 7,
      14, and 25, the distances between the maxillary molars and incisors were measured
      at the experimental and contralateral sides. RESULTS: Changes in measured
      distances at the experimental sides were significantly different between the
      tezosentan and the coil-spring groups on day 25 (P < .001), with the tezosentan
      group showing greater changes in the measured distances. There were no
      differences between the tezosentan and the coil-spring groups at the
      contralateral side. In the control group, the measured distance increased at both
      sides (P < .001). CONCLUSIONS: Tezosentan, an endothelin dual antagonist,
      enhanced tooth movements in rats.

PMID- 16627185
TI  - Correlation between mandibular incisor crown morphologic index and postretention
      stability.
AB  - INTRODUCTION: Considering postretention stability as a result of successful
      orthodontic treatment, we aimed to verify the influence of mandibular-incisor
      crown morphology in the relapse of mandibular anterior crowding. METHODS: The
      sample comprised 56 white subjects of both sexes with Class I and Class II
      malocclusions at pretreatment, treated with extraction of 4 first premolars and
      edgewise mechanics. No patient underwent interproximal stripping during or after
      treatment. Mean pretreatment age was 13.23 years. Mean treatment time was 2.11
      years, and mean posttreatment evaluation time was 5.12 years. Mandibular anterior
      crowding was measured with the Little irregularity index, and the mesiodistal and
      buccolingual proportion of the mandibular incisor crowns was measured with the
      Peck and Peck index. The measurements were obtained from dental casts at the
      pretreatment, posttreatment, and postretention stages. The Pearson correlation
      coefficient was calculated to determine the correlation between mandibular
      incisor-crown morphology and the amount of postretention-crowding relapse.
      RESULTS: The mandibular-incisor-crown morphologic index was not significantly
      correlated with the amount of mandibular-anterior-crowding relapse. CONCLUSIONS:
      Mandibular-incisor-crown morphology is not correlated with the amount of
      mandibular-anterior-crowding relapse.

PMID- 16627186
TI  - Chincup therapy for a young woman with anterior displacement and obtuse angle of
      the mandible in Class I malocclusion.
AB  - INTRODUCTION: Dolichofacial skeletal patterns are a challenge for the
      orthodontist. Even when treatment for a long-face patient begins before the
      adolescent growth spurt, excellent compliance is generally needed. The patient
      whose care is presented here started treatment at age 14. RESULTS: The extraction
      of 4 premolars, rapid palatal expansion, and excellent compliance wearing a
      combination occipital and vertical-pull chincup over a 2-year period led to good
      results at age 16, with minimal dental or skeletal relapse at age 18 years 5
      months.

PMID- 16627187
TI  - Appropriate use of the designation of ABO certification: a statement by the
      American Board of Orthodontics.

PMID- 16627188
TI  - Orthodontics in 3 millennia. Chapter 8: The cephalometer takes its place in the
      orthodontic armamentarium.
AB  - After World War II, cephalometric radiography came into widespread use, enabling
      orthodontists to measure changes in tooth and jaw positions produced by growth
      and treatment. Cephalometrics revealed that many malocclusions resulted from
      faulty jaw relationships, not just malposed teeth, and made it possible to see
      that jaw growth could be altered by orthodontic treatment. Since 1931, a
      multitude of analyses have been developed, whereby the face is inscribed in
      triangles, rectangles, and polygons, permitting the orthodontist to dissect the
      profile into an array of angular and distance measurements. Those who embraced
      too quickly these measurements as a panacea soon learned that they are best taken
      with a grain of good judgment.

PMID- 16627189
TI  - Rapid prototyping as a tool for diagnosis and treatment planning for maxillary
      canine impaction.
AB  - Treating an impacted maxillary canine requires identifying its exact position;
      this can pose a challenge to both orthodontists and oral surgeons. The purpose of
      this article is to present a new method for diagnosis and treatment planning of
      maxillary canine impaction by using computed tomography combined with rapid
      prototyping. Computed tomography image files of a patient with tooth 13 impaction
      were edited to produce, by means of rapid prototyping, an anatomic model of the
      maxillary teeth and a single attachment model that was later used to fabricate a
      metal attachment to be bonded to the impacted tooth. The dental model was used in
      the diagnosis and orthodontic treatment planning, and to communicate with the
      patient and his parents. The model showed the exact anatomical relationship
      between the impacted tooth and the other teeth; it was the main aid in
      intraoperative navigation during surgery to expose the tooth. The metal
      attachment built from the prototype was bonded to tooth 13 during surgery.
      Prototyping could become a new tool for fabricating brackets and other precision
      accessories for specific needs. Dental models made with rapid prototyping could
      become the diagnostic procedure of choice for evaluating impacted maxillary
      canines.

PMID- 16627190
TI  - Phylogeography of Pseudacris regilla (Anura: Hylidae) in western North America,
      with a proposal for a new taxonomic rearrangement.
AB  - The Baja California populations of Pseudacris regilla, a widespread species in
      Western North America ranging from British Columbia to southern Baja California,
      are characterized by extensive geographic fragmentation. We performed
      phylogeographic and historical demographic analyses on 609 bp of the cytochrome b
      mitochondrial gene of 110 individuals representing 28 populations to determine
      the relative influences of current and historical processes in shaping the
      present distribution of genetic diversity on the Baja California Peninsula.
      Haplotypes from this area were nested in a clade with three well-differentiated
      groups. Two of these groups are from Baja California Sur and another is from
      California and Baja California. The estimated date for the split of these groups,
      between 0.9-1 Ma, fits with previously proposed hypotheses of vicariance due to
      different transpeninsular seaways, although successive population fragmentation
      and expansion due to climatic oscillations during Pleistocene glaciations cannot
      be discarded. Historical demographic analyses detected signs of past population
      expansions, especially in the southernmost group. With respect to populations
      north of this region, two older clades were identified, one with haplotypes
      mainly distributed in central California, and the other corresponding to the
      northern half of the species range, in what apparently is a recurrent pattern in
      the Pacific coast of North America. Based on the concordance between mt-DNA and
      available allozyme data indicating that these species have a long independent
      evolutionary history, we propose to consider the three major clades as distinct
      species: P. regilla, P. pacifica, and P. hypochondriaca.

PMID- 16627192
TI  - Epidemiology of vertebral fractures: implications for vertebral augmentation.
AB  - To put vertebral augmentation (eg, vertebroplasty) into perspective, the etiology
      and outcomes of vertebral fractures are reviewed. There is considerable debate
      about which criteria should be used to define a vertebral fracture because there
      is no consistent relation between symptoms and the degree of vertebral deformity.
      However, it is the more significant vertebral body deformities that are most
      closely associated with frequent or severe back pain, and the referrals for
      vertebral augmentation come mainly from this subset of patients. In addition to
      their vertebral fractures, these patients typically have osteoporosis or elevated
      bone turnover, and they are at greatly increased risk of subsequent fractures as
      a result of falling or, more often, excessive spinal loads from activities of
      everyday living. Additional risk factors for new vertebral fractures include the
      number and severity of vertebral deformities at baseline. Moreover, new fractures
      are most likely in nearby vertebrae, and they occur more frequently in the mid
      thoracic or thoracolumbar regions of the spine. Interestingly, these are also the
      characteristics of the subsequent fractures of contiguous vertebrae considered by
      some to represent a complication of vertebral augmentation, yet they characterize
      vertebral fracture risk even in untreated patients. Vertebral fractures are very
      common among older men and postmenopausal women; they are associated with
      substantial morbidity and mortality; and they may have a devastating impact on
      the patient's quality of life. Vertebral augmentation may be able to help many of
      these patients, although opportunities exist to optimize management strategies
      with respect to the other factors that influence long-term outcomes in this
      patient population.

PMID- 16627193
TI  - Randomized vertebroplasty trials: Current status and challenges.

PMID- 16627194
TI  - Evidence on the effectiveness and cost-effectiveness of vertebroplasty: A review
      of policy makers' responses.
AB  - This review paper tracks the growth in the evidence supporting the use of
      percutaneous vertebroplasty for painful osteoporotic vertebral compression
      fractures. The rapidly increasing numbers of publications in the literature
      between 1994 and 2004 are documented. Despite the relatively large volume of
      research on this topic, several technology appraisals undertaken by international
      health policy makers reported inadequate high-quality evidence. Policy makers'
      reimbursement decisions for vertebroplasty and their options when faced with
      imperfect evidence are discussed.

PMID- 16627195
TI  - Mentoring the mentors: Aligning mentor and mentee expectations.
AB  - The Radiology Alliance for Health Services Research sponsored a symposium at the
      2005 Annual Meeting of the Association of University Radiologists, which focused
      on the issue of aligning mentor and mentee expectations to foster successful
      mentoring relationships. This article presents a summary of the informal
      discussion of the panelists' individual experiences, common themes, and insights
      gained from the panel participants.

PMID- 16627196
TI  - Clinical decision rules in radiology.
AB  - Clinical decision rules to guide physicians in the appropriate use of diagnostic
      imaging studies need to be developed, in part, to control the overutilization of
      imaging studies. These rules need to be evidence based. Randomized control trials
      can be designed to assess the value of imaging studies and interventional
      procedures at levels five and six, patient outcome and societal efficacies, in
      Fryback and Thornbury's hierarchical model of efficacy. Results of these trials
      can be used to develop clinical decision rules. However, the efficacy of most
      diagnostic imaging studies can be assessed better at levels three and four,
      diagnostic thinking and therapeutic efficacies. Studies can be designed to
      determine clinical situations in which imaging studies will be of no value or to
      determine clinical criteria for the use of imaging studies. Systematic reviews of
      the literature and other techniques of analysis of evidence, such as decision
      trees, also can be used to develop evidence-based clinical decision rules for the
      use of diagnostic imaging procedures.

PMID- 16627197
TI  - Statistical combination schemes of repeated diagnostic test data.
AB  - RATIONALE AND OBJECTIVES: When diagnostic tests are repeated and combined, a
      number of schemes may be adopted. Guidelines for their interpretations are
      required. MATERIALS AND METHODS: Three combination schemes, "and" (A), "or" (O),
      and "majority" (M), are considered. To evaluate these schemes, dependency by
      specifying kappa values quantifying repeated test agreement was structured. In a
      pilot study, the combined accuracies of magnetic resonance imaging using six
      different pulse sequences of medial collateral ligaments of the elbows of 28
      cadavers, with eight having lesions artificially created surgically, were
      examined. Images were evaluated simultaneously by using a five-point ordinal
      scale. For each pulse sequence, individuals for whom the diagnosis varied from
      once to three repetitions were considered. RESULTS: Scheme M improves diagnostic
      accuracy when sensitivity and specificity of a single test exceed 0.5, with
      maximal improvement at 0.79. Under scheme A, sensitivity decreases to 0.38-0.59.
      Under scheme O, sensitivity increases to 0.53-0.79. Scheme M yields a small
      improvement, reaching 0.50-0.71. Under scheme A, specificity increases to 0.95
      0.98. Under scheme O, specificity decreases to 0.91-0.98. Scheme M also yields a
      small improvement, reaching 0.94-0.98. CONCLUSION: Scheme A is recommended for
      ruling in diagnoses, scheme O is recommended for ruling out diagnoses, and scheme
      M is neutral. Consequently, different schemes may be used to optimize the target
      diagnostic accuracy.

PMID- 16627198
TI  - Radiographic and clinical predictors of bladder rupture in blunt trauma patients
      with pelvic fracture.
AB  - RATIONALE AND OBJECTIVES: Bladder rupture is a potentially serious injury in
      blunt trauma patients. We determined whether location and displacement of pelvic
      fractures and the degree of hematuria can accurately predict bladder injury.
      MATERIALS AND METHODS: A retrospective database of 721 blunt trauma pelvic
      fractures that presented to a single large regional level 1 trauma center between
      January 1, 1997, and July 15, 2003, was expanded to include data on bladder
      injury and the initial urinalysis. Multiple logistic regression was performed to
      determine if an association exists between pelvic fracture pattern, degree of
      hematuria, and bladder injury. A potential clinical prediction rule was then
      derived using a point system for four independent, significant risk factors
      identified from the logistic regression results. RESULTS: There were 37 bladder
      ruptures (5.0%), all of which presented with hematuria >30 red blood cells per
      high-powered field (RBC/HPF). Pelvic injuries that were independently associated
      with bladder injury included diastasis of the pubic symphysis >1 cm, RR = 9.8
      (95% CI 4.6-20.9), and fracture of the obturator ring with displacement >1 cm RR
      = 3.2 (95% CI 1.6-6.5). No patient with isolated acetabular fractures sustained
      bladder injury. A clinical prediction rule was derived, consisting of a single
      point for each of the significant pelvic injury sites in patients with hematuria
      >30 RBC/HPF. Patients with a prediction score of 0 had a 2.3% probability of
      bladder injury, whereas patients with scores of 1 and 2 had probabilities of
      bladder injury of 9.2% and 43.7%, respectively. CONCLUSIONS: Patients with
      isolated acetabular fractures and patients with <30 RBC/HPF did not sustain
      bladder injury. In addition to hematuria, specific pelvic injury patterns are
      associated with bladder rupture. If validated, a clinical prediction rule derived
      from this data has the potential to guide the care of the blunt trauma patient.

PMID- 16627199
TI  - Inference and uncertainty in radiology.
AB  - This paper seeks to enhance understanding of the philosophical underpinnings of
      our discipline and the resulting practical implications. Radiology reports exist
      in order to convey new knowledge about a patient's condition based on empiric
      observations from anatomic or functional images of the body. The route to
      explanation and prediction from empiric evidence is mostly through inference
      based on inductive (and sometimes abductive) arguments. The conclusions of
      inductive arguments are, by definition, contingent and provisional. Therefore, it
      is necessary to deal in some way with the uncertainty of inferential conclusions
      (i.e. interpretations) made in radiology reports. Two paradigms for managing
      uncertainty in natural sciences exist in dialectic tension with each other. These
      are the frequentist and Bayesian theories of probability. Tension between them is
      mirrored during routine interactions among radiologists and clinicians. I will
      describe these core issues and argue that they are quite relevant to routine
      image interpretation and reporting.

PMID- 16627200
TI  - Loss of anteroposterior intralobar attenuation gradient of the lung: Correlation
      with pulmonary function.
AB  - RATIONALE AND OBJECTIVES: Since the initial description of an intralobar
      attenuation gradient by Webb et al, it has been suggested that departure from the
      intralobar attenuation gradient could indicate early lung diseases. However, its
      significance has not been determined in detail. We aimed to quantify the
      anteroposterior intralobar attenuation gradient on volumetric end-inspiratory and
      end-expiratory high-resolution computed tomography (CT) in patients with
      emphysema and to correlate the gradient values with pulmonary function. MATERIALS
      AND METHODS: The study population consisted of 21 consecutive patients with
      emphysema evaluated with volumetric expiratory high-resolution CT and 6 patients
      with normal high-resolution CT findings. The anteroposterior intralobar
      attenuation gradient values were quantified on end-inspiratory and end-expiratory
      sagittal reformations using a lung analysis software program and were correlated
      with pulmonary function tests results. RESULTS: The intralobar attenuation
      gradient values in patients with forced expiratory volume in 1 second (FEV1) < or
      =70% were significantly smaller compared with those in patients with FEV1 >70% in
      bilateral lower lobes at end-expiration (P = .0061, P = .047, respectively,
      unpaired t-test). The FEV1 values in patients with attenuation gradient values <
      or =0.02 were significantly lower than in those with attenuation gradient values
      >0.02 (right lower lobe: P = .024; left lower lobe: P = .0034; chi-squared test).
      The intralobar attenuation gradient values in bilateral lower lobes at end
      expiration were significantly correlated with FEV1 and FEV1/forced vital capacity
      (right: P = .031, P = .039, respectively; left: P = .036, P = .030, respectively,
      Pearson correlation). CONCLUSIONS: The quantitative measurement of the
      anteroposterior intralobar attenuation gradient values of the lung showed that
      these gradients at end-expiration in both lower lobes correlate with obstructive
      physiology.

PMID- 16627201
TI  - PET and planar imaging of tumor hypoxia with labeled metronidazole.
AB  - RATIONALE AND OBJECTIVES: This study was aimed to develop 99mTc- and 68Ga-labeled
      metronidazole (MN) using ethylenedicysteine (EC) as a chelator and evaluate their
      potential use to assess tumor hypoxia. MATERIALS AND METHODS: EC-MN was labeled
      with 99mTc in the presence of tin (II) chloride. Labeling EC-MN with 68Ga was
      achieved by adding 68GaCl3 (2 mCi with 3.4 microg cold GaCl3). In vitro cellular
      uptakes of 99mTc- and 68Ga-EC-MN were obtained in various types of tumor cells at
      0.5-4 hours. Tissue distribution and PET imaging of 99mTc and 68Ga-EC-MN were
      evaluated in breast tumor-bearing rats at 0.5-4 hours. Tumor oxygen tension was
      measured using an oxygen probe. RESULTS: There were similar cellular uptakes (2
      10%) between 99mTc- and 68Ga-EC-MN at 0.5-4 hours. In vivo biodistribution of
      99mTc- and 68Ga-EC-MN in breast tumor-bearing rats showed increased tumor-to
      blood and tumor-to-muscle count density ratios as a function of time. Positron
      emission tomography images confirmed that the tumors could be visualized clearly
      with 68Ga-EC-MN. Oxygen tension in tumor tissue was determined to be 6-10 mm Hg
      compared with 40-50 mm Hg in normal muscle tissue. CONCLUSIONS: The results
      indicated that it is feasible to use 99mTc- and 68Ga-EC-MN for assessment of
      tumor hypoxia. These agents may be useful in selecting and evaluating cancer
      therapy.

PMID- 16627202
TI  - CT angiography of peripheral arterial bypass grafts: Accuracy and time
      effectiveness of quantitative image analysis with an automated software tool.
AB  - RATIONALE AND OBJECTIVES: Qualitative analysis of computed tomography (CT)
      angiography data often is limited by intra- and interobserver variability. The
      purpose of this study was to evaluate the time-effectiveness and accuracy of a
      quantitative CT angiography data analysis using automated software in comparison
      with qualitative axial and coronal CT image reading in patients with peripheral
      bypass grafts. MATERIALS AND METHODS: Twenty-eight patients with 33 saphenous
      bypass grafts underwent 4-channel (n = 21) and 16-channel (n = 7) CT angiography.
      Two readers evaluated in consensus the CT data qualitatively on axial and coronal
      reconstructions and with the software regarding the presence of graft stenoses,
      aneurysmal changes, and arteriovenous fistulas. The time for data analysis was
      taken and the accuracy was compared with the results from digital subtraction
      angiography (DSA). RESULTS: No significant difference was present between data
      analysis time using axial and coronal CT images (4.9 +/- 1.5 minutes) and when
      using the software tool (5.5 +/- 1.4 minutes). Good (kappa = 0.652) to excellent
      (kappa = 1.000) intermodality agreement was present between qualitative and
      quantitative CT analysis regarding graft-related abnormalities. Sensitivity and
      specificity for diagnosing stenoses, aneurysms, and fistula did not differ
      significantly (P > .025) between qualitative CT image reading and the automated
      software tool. CONCLUSIONS: CT angiography analysis of peripheral bypass grafts
      using an automated software tool is similar regarding time-effectiveness and
      accuracy when compared with qualitative CT data analysis on axial and coronal
      images. It may assist in determining the significance of an abnormality and can
      yield objective morphometric data of vessel calibers.

PMID- 16627203
TI  - Consensus review: A method of assessment of calcifications that appropriately
      undergo a six-month follow-up.
AB  - RATIONALE AND OBJECTIVES: Breast calcifications seen on mammography may be
      associated with benign conditions or malignancies. Accurate characterization of
      these calcifications is crucial to providing optimal care that may spare women
      unnecessary biopsies and appropriately allow interval mammography. The purpose of
      this study is to determine if consensus characterization of calcifications by two
      breast imaging experts using standardized criteria can establish that follow-up
      is a safe option. MATERIALS AND METHODS: For this retrospective study, our breast
      imaging database was reviewed and the cases imaged between the years 1999 and
      2001 were used to identify patients with calcifications who were recommended for
      a six-month follow-up or biopsy. All cases had been prospectively assessed by at
      least two expert breast imagers using standardized features to assess the
      findings before a recommendation for follow-up or a biopsy was made. A
      retrospective chart review examining the radiology reports was done to determine
      the percentage of women from each of the two groups who developed malignancies.
      RESULTS: Of 744 patients who had mammographically identified clusters of
      calcifications, 490 clusters (409 single and 81 multiple) were diagnosed as
      probably-benign, and a short-interval 6-month follow-up was recommended. Of these
      calcifications followed for three years, only two (0.5%) of the single clusters
      proved to be malignant, and malignancy was diagnosed at the 12-month follow-up
      examination. In both cases, the women were diagnosed with ductal carcinoma in
      situ (DCIS). Of 254 clusters recommended for biopsy, 242 (215 single and 27
      multiple) underwent biopsy. A total of 70 cancers were diagnosed: 54 (77.1%) were
      DCIS and 16 (22.9%) were primary invasive mammary carcinoma (10 cases of invasive
      ductal carcinoma, 3 cases of invasive lobular carcinoma, 2 cases of invasive
      ductal carcinoma with DCIS, and one case of invasive mucinous carcinoma with
      DCIS). Twenty-nine percent of women who had a biopsy performed had calcifications
      associated with malignancy. In contrast, in the women whose calcifications were
      followed by mammography, only 0.5% went on to develop malignancies. CONCLUSION:
      Consensus review of calcifications by two breast imagers using standardized
      criteria is a safe follow-up option.

PMID- 16627204
TI  - Automatic selection of the optimal cardiac phase for gated three-dimensional
      coronary x-ray angiography.
AB  - RATIONALE AND OBJECTIVES: For the reconstruction of the coronary arteries from
      rotational angiography data, a crucial point is the selection of the optimal
      cardiac phase for data reconstruction. To avoid time-consuming interactive
      selection of the optimal cardiac phase by visual inspection of multiple high
      resolution data sets reconstructed at different cardiac phases, an automatic
      approach for deriving optimal reconstruction windows is attractive. MATERIALS AND
      METHODS: This paper presents a new approach to fully automatic selection of the
      optimal cardiac phase for image reconstruction. It is based on the analysis of a
      four-dimensional data set of the region of interest reconstructed at low-spatial
      resolution utilizing an image quality index, which quantifies the image quality
      of a single three-dimensional reconstructed volume. The derived image quality
      index utilizes the histogram information of a single temporal snapshot as a
      quality measure for the vessel reconstruction. The proposed technique was applied
      to 16 projection data sets obtained in eight pigs. RESULTS: Experiments to
      evaluate the proposed method based on user-defined image quality parameters
      serving as ground truth, showed a relatively high correlation (>84%) for high
      quality (c(phi) > 0.95) images. CONCLUSION: An image-based technique is
      introduced, which is able to determine the optimal cardiac phase for 3D-RCA fully
      automatically. The proposed method was successfully applied to 16 data sets
      obtained in a total of 8 porcine models.

PMID- 16627205
TI  - Keys to educator effectiveness in radiology.
AB  - Knowing what makes an educator effective is a key step in becoming an effective
      educator. There is a paucity of literature on this subject related specifically
      to radiology, but the tenets of effective teaching and learning can be applied to
      all educational domains. The desired outcome of all educators is motivation of
      students to learn. Put in this perspective, the primary role of the teacher is
      that of a facilitator. The teacher must possess enough knowledge in his or her
      domain to demonstrate credibility to students. He or she must be able to create
      effective learning environments and effectively communicate with students. In
      addition to demonstrating these and other skills, an effective educator must act
      as a role model for professional behavior. By doing so, he or she encourages
      students to become life-long learners who will make positive contributions to the
      world in which they live and work.

PMID- 16627206
TI  - Three-dimensional X-ray coronary angiography in the porcine model: A feasibility
      study.
AB  - RATIONALE AND OBJECTIVES: Three-dimensional high-spatial-resolution angiograms of
      the coronary arteries were acquired with an electrocardiogram-gated three
      dimensional rotational angiography technique on an interventional X-ray system.
      MATERIALS AND METHODS: During selective injection of contrast material in the
      left and right coronary artery, projection images were obtained in eight pigs
      during a continuous rotation of the X-ray gantry over an angular range of 180
      degrees within 8 seconds. RESULTS: Three-dimensional tomographic reconstruction
      depicted the proximal, medial, and distal sections of the main arteries as well
      as the main bifurcations in multiple cardiac phases in all animals. CONCLUSIONS:
      For the first time, this feasibility study shows that a three-dimensional
      angiogram of the coronary arteries can be obtained intraprocedurally in a
      conventional interventional suite by means of tomographic reconstruction from
      projection images.

PMID- 16627207
TI  - Rapid and automatic calculation of the midsagittal plane in magnetic resonance
      diffusion and perfusion images.
AB  - RATIONALE AND OBJECTIVES: A near real-time and fully automatic method for
      calculation of the midsagittal plane (MSP) for magnetic resonance (MR) diffusion
      and perfusion images is introduced. MATERIALS AND METHODS: The method is based on
      the Kullback-Leibler's (KL) measure quantifying the difference between two
      intensity distributions. The MSP is a sagittal plane with the highest KL measure.
      The method was validated quantitatively for 61 diffusion-weighted imaging (DWI),
      cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT),
      peak height (PKHT), and time to peak (TPP) data sets of 11 stroke patients based
      on the ground truth provided by two raters. RESULTS: Average angular errors are
      less than 1 degrees for DWI and less than 2 degrees for CBF and CBV. Average
      distance errors measured in the worst case (on the brain's bounding box) are less
      than 2.5 mm for DWI and less than 5 mm for CBF and CBV. This algorithmic accuracy
      is at the level of interrater variability. Results obtained for the other
      perfusions maps (MTT, PKHT, TTP) were inferior; therefore, processing of CBF or
      CBV is preferred for accurate and robust calculation of the MSP from perfusion
      maps. Calculation of the MSP takes about half a second on a standard computer.
      CONCLUSIONS: The proposed method is near real-time and fully automatic, and
      neither user interaction nor parameter setting is needed. It does not require
      preprocessing of data. The method potentially is useful in rapid and automated
      processing of MR stroke diffusion and perfusion images.

PMID- 16627210
TI  - An initial evaluation of pelvic floor function and quality of life of bladder
      exstrophy patients after ureterosigmoidostomy.
AB  - Classic bladder exstrophy is characterized by displaced pelvic floor musculature
      and significant skeletal and genitourinary defects. A paucity of data exist
      evaluating long-term pelvic floor function in exstrophy patients after
      ureterosigmoidostomy. This study is an initial attempt to evaluate the prevalence
      of urofecal incontinence, pelvic organ prolapse, and overall quality of life in
      patients who have had ureterosigmoidostomies. Fifty-two individuals who underwent
      ureterosigmoidostomy between 1937 and 1990 were identified through the
      Ureterosigmoidostomy Association and the Johns Hopkins bladder exstrophy database
      and mailed questionnaires approved by the Institutional Review Board (Johns
      Hopkins). Data were analyzed with SigmaStat 3.0 (SPSS, Inc., Chicago, IL). Eighty
      three percent of the subjects responded, with a mean age of 44.4 years (range, 14
      73 years) and mean of 40.9 years (range, 14-65 years) after ureterosigmoidostomy.
      Prevalence of daily urinary and fecal incontinence was 48% (n = 20) and 26% (n =
      11), respectively, whereas the prevalence of weekly combined urofecal
      incontinence was 63% (n = 27). The incidence of pelvic organ prolapse in this
      cohort was 48% (n = 20). In these patients, a significant risk of urofecal
      incontinence and pelvic organ prolapse exists. Long-term follow-up studies are
      needed to understand the role of pelvic floor musculature in this complex birth
      defect.

PMID- 16627211
TI  - Early perioperative outcomes and pancreaticoduodenectomy in a general surgery
      residency training program.
AB  - Current trends in national health care are triggering a reassessment of training
      in general surgery. Currently, 75% of general surgery residents seek postgraduate
      fellowship training, and significant debate has occurred regarding the best
      manner for surgeons to acquire competency in performing complex operations.
      Pancreaticoduodenectomy (PD) is a complex procedure performed infrequently by
      most surgical graduates. From 1990 through 1997, the average number of PD
      operations performed per general surgery graduate ranged from 1.5 to 2.5. We
      examine the surgical outcomes following PD performed by surgical resident staff
      in a university-based general surgery training program. Between January 2001 and
      October 2004, 164 patients underwent PD for periampullary disease. Data were
      prospectively entered into a computerized database, including resident
      participation. We analyzed 30-day mortality and morbidity rates. Perioperative
      outcomes were 30-day mortality (2.2%), pancreatic fistula (6.1%), reoperation
      (2.2%), average length of hospital stay (13.5 days), mean operating time (489
      minutes), and median estimated blood loss (1274 ml per case). PD can be performed
      with an acceptable morbidity and mortality within the teaching structure of a
      general surgery training program. These outcomes are likely related to the
      performance of PD at a high-volume, tertiary center by a single surgeon and
      compare favorably to best-practice benchmark outcomes.

PMID- 16627212
TI  - Postchemotherapy characteristics of hepatic colorectal metastases: remnants of
      uncertain malignant potential.
AB  - Accepted management for colorectal cancer (CRC) involves resection of the primary
      neoplasm and chemotherapy; the debate continues over the most beneficial order of
      these components. Preoperative chemotherapy aimed at liver metastases may result
      in complete pathologic response and replacement of the malignancy with scar. The
      McGill University liver diseases database was retrospectively reviewed. Forty-one
      patients receiving treatment between December 2003 and August 2004 were
      identified, their medical records examined, and liver histology reviewed. The
      histology of the remnants was linked to the appearance of the lesions on
      preresection imaging and to the primary colorectal neoplasms. Twenty-seven of the
      41 patients (66%) received preoperative chemotherapy (oxaliplatin or irinotecan).
      Features of the primary neoplasm that predicted resolution of the metastases were
      absence of tumor budding (P = 0.04), absence of a diffusely infiltrative tumor
      margin (P = 0.02), and loss of expression of the DNA repair gene O6-methylguanine
      DNA methyltransferase (P = 0.08). Oxaliplatin and irinotecan demonstrate
      beneficial effects in treating hepatic colorectal metastases and should be
      considered in such patients before resection. We propose the acronym RUMP to
      denote the remnants of uncertain malignant potential remaining. Further
      investigation is required to determine any correlation between the drug received
      and the resulting lesion.

PMID- 16627213
TI  - The usefulness of drain data to identify a clinically relevant pancreatic
      anastomotic leak after pancreaticoduodenectomy?
AB  - Pancreatic anastomotic leak (leak) remains a persistent problem after
      pancreaticoduodenectomy (PD). Recent reports indicate a mean occurrence of 10%
      with a range of 2%-28% of patients. However, valid comparisons for these studies
      cannot be made because the definition of leak is variable, and many patients
      deemed to have a leak are not sick. The aim of this study was to determine the
      meaning of the volume and amylase content of the effluent from surgical drains by
      comparing these values to actual clinical outcomes. From January 1996 to July
      2002, 207 consecutive patients underwent PD. We considered a leak to be present
      if greater than 30 ml/day of drainage was observed from drains and if that
      drainage contained an amylase-rich fluid (greater than 5X serum) on or after
      postoperative day (POD) 5. Cases were then divided into three groups-no leak,
      chemical leak only (leak but asymptomatic), and a clinical leak group (leak that
      required therapeutic intervention, reoperation, readmission, or prolonged length
      of stay). Then the drainage volume and its amylase concentration for every
      postoperative day were compared between the three groups. There were no operative
      or hospital deaths, and the mean length of stay (LOS) was 11.2 +/- 6.1 days.
      Prolonged LOS was set at greater than 17 days (one standard deviation beyond the
      mean LOS for all cases). Leak was observed in 14% of cases (n = 29) and the
      patients were subsequently divided into these groups: no leak (n = 178), chemical
      leak only (n = 12), and clinical leak (n = 17). Surprisingly, the daily drain
      amylase values did not differ between the chemical leak group and the clinical
      leak group. The daily volume of drainage on POD 5-8 for the clinical leak group
      was significantly greater than the volumes of the other two groups, so that a
      combination of greater than 200 ml/day of drainage on POD 5 with an amylase
      greater than 5X serum had a positive predictive value (PPV) of 84% and a negative
      predictive value (NPV) of 99% for a clinically relevant leak. We used broad
      criteria from drainage effluent to include as many potential leaks as possible.
      This broad definition of leak selected 14% of the PD patients as having a leak;
      within this group, all of the clinical complications of leak occurred. By
      increasing the volume criteria from greater than 30 ml per day to greater than
      200 ml per day, the PPV was increased from 59% to 84% while keeping NPV at 99%.
      Drain data based on the volume and amylase criteria of this study may be useful
      for early detection of a leak that will have clinical impact. This study's
      criteria for leak may be a good definition to design a clinical trial.

PMID- 16627214
TI  - Combined antioxidant therapy reduces pain and improves quality of life in chronic
      pancreatitis.
AB  - Patients with chronic pancreatitis (CP) typically suffer intractable abdominal
      pain that is resistant to most analgesic strategies. Recent research indicates
      that the pain of CP may be in part due to oxygen free radical induced pancreatic
      damage. Using a randomized, double-blind, placebo-controlled crossover trial, we
      evaluated the efficacy of a combined antioxidant preparation in the management of
      CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to
      receive treatment with either Antox, which contains the antioxidants selenium,
      betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each
      group of patients then switched to receive the alternative treatment for a
      further 10 weeks. Markers of antioxidant status were measured by blood sampling,
      whereas quality of life and pain were assessed using the SF-36 questionnaire.
      Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox
      was associated with significant improvements in quality of life in terms of pain
      (+17 antioxidant vs. -7 placebo), physical (+9 vs. -3) and social functioning (+8
      vs. -7), and general health perception (+10 vs. -3). We conclude that treatment
      with antioxidants may improve quality of life and reduce pain in patients
      suffering from chronic pancreatitis.

PMID- 16627215
TI  - Long-term results of Frey's procedure for chronic pancreatitis: a longitudinal
      prospective study on 40 patients.
AB  - Only limited prospective data are available regarding the long-term outcome of
      local resection of the pancreatic head in combination with longitudinal
      pancreaticojejunostomy in patients with chronic pancreatitis. From 1997 to 2001,
      40 patients affected by chronic pancreatitis were subjected to the Frey's
      procedure. Preoperative selection criteria included confirmed diagnosis of
      chronic pancreatitis, dilation of Wirsung's duct to a diameter greater than 6 mm,
      and the absence of obstructive chronic pancreatitis secondary to fibrotic
      stenosis at the pancreatic body or tail. Preoperative pain was present in 38
      cases (95%), and follow-up was performed in all patients at least once yearly up
      to 2003 (median 60 months, inter percentile range 20.1-79.6). Postoperative
      morbidity occurred in three cases (7.5%). The percentage of pain-free patients
      was 94.7%, 93.7%, 87.5%, and 90% at 1, 2, 3, and 4/5 years after surgical
      operation, respectively. After surgery, three patients developed diabetes. Both
      the body mass index and quality of life showed statistically significant
      improvements at all follow-up intervals. Whenever surgery is indicated, the short
      term and long-term outcomes confirm that Frey's procedure is an appropriate means
      of management for patients with chronic pancreatitis in the absence of doubts of
      neoplasia and/or distal ductal obstruction.

PMID- 16627216
TI  - Patterns of recurrence after curative resection of pancreatic cancer, based on
      autopsy findings.
AB  - The autopsy findings of patients who died of recurrence after curative resection
      of pancreatic cancer may afford a reliable guide to increase long-term survival
      after surgery. Recurrence patterns were analyzed for 27 autopsied patients who
      had undergone potentially curative resection of pancreatic cancer. The pattern of
      recurrence was classified as follows: (1) local recurrence, (2) hepatic
      metastasis, (3) peritoneal dissemination, (4) para-aortic lymph node metastasis,
      and (5) distant metastasis not including hepatic metastasis, peritoneal
      dissemination, and para-aortic lymph node metastasis. Of the 27 autopsied
      patients, recurrence was confirmed for 22 of 24 patients, except for three who
      died of early postoperative complications. Eighteen (75%) of the 24 patients had
      local recurrence, 12 (50%) had hepatic metastasis, and 11 (46%) had both. For
      four patients, local recurrence confirmed by autopsy was undetectable by computed
      tomography, because the recurrent lesions had infiltrated without forming a tumor
      mass. Peritoneal dissemination, para-aortic lymph node metastasis, and distant
      metastasis were found for eight (33%), five (21%), and 18 (75%) of the cases,
      respectively. Twenty patients died of cancer, but local recurrence was judged to
      be the direct cause of death of only four. Local recurrence frequently occurs,
      but is rarely a direct cause of death, and most patients died of metastatic
      disease. Therefore, treatment that focuses on local control cannot improve the
      survival of patients with resectable pancreatic cancer, and thus, treatment
      regimens that are effective against systemic metastasis are needed.

PMID- 16627217
TI  - Aortic occlusion balloon catheter technique is useful for uncontrollable massive
      intraabdominal bleeding after hepato-pancreato-biliary surgery.
AB  - Massive intraabdominal hemorrhage sometimes requires urgent hemostatic surgical
      intervention. In such cases, its rapid stabilization is crucial to reestablish a
      general hemodynamic status. We used an aortic occlusion balloon catheter in
      patients with massive intraabdominal hemorrhage occurring after hepato-pancreato
      biliary surgery. An 8-French balloon catheter was percutaneously inserted into
      the aorta from the femoral artery, and the balloon was placed just above the
      celiac artery. Fifteen minutes inflation and 5 minutes deflation were alternated
      during surgery until the bleeding was surgically controlled. An aortic occlusion
      balloon catheter was inserted on 13 occasions in 10 patients undergoing
      laparotomy for hemostasis of massive hemorrhage. The aorta was successfully
      occluded on 12 occasions in nine patients. Both systolic pressure and heart rate
      were normalized during aortic occlusion, and the operative field became clearly
      visible after adequate suction of leaked blood. Bleeding sites were then easily
      found and controlled. Hemorrhage was successfully controlled in 7 of 10 patients
      (70%), and they were discharged in good condition. The aortic occlusion balloon
      catheter technique was effective for easily controlling massive intraabdominal
      bleeding by hemostatic procedure after hepato-pancreato-biliary surgery.

PMID- 16627218
TI  - Influence of bactibilia after preoperative biliary stenting on postoperative
      infectious complications.
AB  - The aim of this study was to correlate the bactibilia found after preoperative
      biliary stenting with that of the bacteriology of postoperative infectious
      complications in patients with obstructive jaundice. One hundred thirty-eight
      patients (83% malignant and 17% benign etiologies) with obstructive jaundice had
      both their bile and all postoperative infectious complications cultured. Eighty
      six (62%) had preoperative biliary stents (stent group) and 52 (38%) did not (no
      stent group). There were no differences for age, sex, incidence of malignancy,
      type of operation, estimated blood loss, transfusion requirements, hospital
      length of stay, morbidity, or mortality rates between the two groups. Of 31
      infectious complications, 23 were in the stent group and eight were in the no
      stent group (P > 0.05), but only 13 (42%) infectious complications had bacteria
      that were also cultured from the bile. Only wound infection (P = 0.03) and
      bacteremia (P = 0.04) were more likely to occur in stented patients. Taken
      together, these data show that preoperative biliary stenting increases the
      incidence of bactibilia, bacteremia, and wound infection rates but does not
      increase morbidity, mortality, or hospital length of stay. Jaundiced patients can
      undergo preoperative biliary stenting while maintaining an acceptable
      postoperative morbidity rate.

PMID- 16627219
TI  - Oncolytic herpes viral therapy is effective in the treatment of hepatocellular
      carcinoma cell lines.
AB  - The rising incidence of hepatocellular carcinoma (HCC) in western countries,
      along with the poor prognosis offered by present-day treatment modalities, makes
      novel therapies for this disease necessary. Oncolytic herpes simplex viruses
      (HSV) are replication-competent viruses that are highly effective in the
      treatment of a wide variety of experimental models of human malignancies. This
      study seeks to investigate the effectiveness of oncolytic herpes viruses in the
      treatment of primary HCC cell lines. Sixteen commercially available human HCC
      cell lines were studied. G207 is an attenuated, replication-competent, oncolytic
      HSV engineered to selectively replicate within cancer cells. Cell lines were
      tested for viral sensitivity to G207 and their ability to support viral
      replication using standard cytotoxicity and viral replication assays. Eleven of
      16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC
      cell lines additionally demonstrated the ability to support viral replication in
      vitro with as high as 800-fold amplification of the administered viral dose
      observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines
      in vitro. From these data, we suggest that oncolytic HSV therapy may have a role
      in the treatment of HCC, and in vivo studies are warranted.

PMID- 16627220
TI  - Arterioportal fistulas: introduction of a novel classification with therapeutic
      implications.
AB  - Arterioportal fistulas (APFs) are arteriovenous communications between the
      splanchnic arteries and the portal vein that represent an infrequent cause of
      presinusoidal portal hypertension. They can be acquired or congenital.
      Penetrating hepatic trauma, including liver biopsies, represent the most common
      etiology. They can be asymptomatic or manifest with portal hypertension. An
      abdominal bruit is a valuable physical finding. Persistence of an APF can cause
      hepatoportal sclerosis and possibly portal fibrosis. A detailed radiologic
      evaluation is mandatory. One must differentiate between small peripheral
      intrahepatic APFs (type 1) and large central APFs (type 2). The former usually
      resolve spontaneously, whereas the latter can cause portal hypertension and
      hepatic parenchymal changes. Type 1 APFs caused by needle injury can be followed
      by Doppler ultrasound. All other fistulas need treatment. Arterioportal fistulas
      are first treated by transcatheter embolization. Surgical approaches are reserved
      for complex cases. Congenital APFs (type 3) are diffuse and intrahepatic and can
      be difficult to manage. Overall, the prognosis is good. Herein, we propose a
      novel classification for arterioportal fistulas with therapeutic implications.

PMID- 16627221
TI  - Helicobacter pylori extract induces nuclear factor-kappa B, activator protein-1,
      and cyclooxygenase-2 in esophageal epithelial cells.
AB  - Helicobacter pylori infection is recognized as the major cause of gastritis and
      gastric cancer; however, its role in the development of gastroesophageal reflux
      disease and Barrett's adenocarcinoma is unclear. The expression of NF-kappaB, AP
      1, and COX-2 may be important in inflammation and tumorigenesis in the esophagus.
      The aim of this study was to examine the effect of live H pylori or H pylori
      extract (HPE) on these factors in the esophageal epithelial cell lines SKGT-4 and
      OE33. NF-kappaB and AP-1 activity were assessed by gel shift assay and COX-2 by
      Western blotting. Coculture of SKGT-4 and OE33 with live H pylori and HPE induced
      NF-kappaB and AP-1 DNA-binding activity, and also decreased IkappaB-alpha levels.
      Treatment with the specific MEK1/2 MAPK inhibitor PD98059, but not the p38 MAPK
      inhibitor SB203580, inhibited NF-kappaB and AP-1 activity. The antioxidant
      vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1
      expression. Moreover, HPE induced COX-2 expression and IL-8 production, and
      PD98059 inhibited COX-2 expression, ERK1/2 phosphorylation, and IL-8 production.
      These data demonstrate that both live H pylori and HPE induce NF-kappaB and AP-1
      expression in esophageal epithelial cells. The induction of such transcription
      factors may play a role in the specific immune response within Barrett's mucosa
      and may indirectly cause inflammation of the gastric cardia and the distal
      esophagus.

PMID- 16627222
TI  - Minimally invasive surgery for gastric stromal cell tumors: intermediate follow
      up results.
AB  - Laparoscopic wedge resection of the stomach (LWS) has become the treatment of
      choice for patients with benign gastric tumors. The technical consideration and
      long-term follow-up data of LWS for gastrointestinal stromal tumors (GISTs) of
      the stomach are limited. We present our experience of 28 LWSs for gastric GISTs
      with a mean follow-up of 43 months. From October 1995 to December 2002, we
      successfully performed 28 LWSs for 29 patients with GISTs of the stomach, and one
      patient needed conversion to laparotomy because of suspected bowel injury when
      establishing pneumoperitoneum. Patient demographics, perioperative parameters,
      and outcomes of the 28 patients were assessed retrospectively. The tumors were
      located in the upper third of the stomach in 13 patients, in the middle third, in
      eight patients, and in the lower third, in seven patients. The mean size of
      tumors was 3.4 +/- 1.6 cm in diameter. The duration of operation ranged from 95
      to 390 minutes: 189.6 +/- 79.5 minutes with the stapler method and 194.3 +/- 50.5
      minutes with the hand-sewn method (P = 0.8870). No blood transfusion was given in
      the perioperative period in all cases. Cholecystectomy in three patients and
      repair of hiatal hernia in one patient were performed during the same operation.
      The oral intake was restored at the third to fourth postoperative days. The
      hospital stay ranged from 3 to 11 days (mean, 6.7 +/- 1.8 days). The follow-up
      period ranged from 12 to 95 months (mean, 43.3 +/- 23.5 months, median 42
      months). There has been no evidence of tumor recurrence, including one patient
      with microscopic invasion of section margin. LWS can be performed safely with a
      satisfactory remission rate for patients with gastric stromal cell tumors.

PMID- 16627223
TI  - Efficacy and safety of ertapenem versus piperacillin-tazobactam for the treatment
      of intra-abdominal infections requiring surgical intervention.
AB  - Complicated intra-abdominal infections usually mandate prompt surgical
      intervention supplemented by appropriate antimicrobial therapy. The aim of this
      study was to demonstrate that ertapenem was not inferior to piperacillin
      tazobactam for the treatment of community-acquired intra-abdominal infections. A
      randomized open-label active-comparator clinical trial was conducted at 48
      medical centers on four continents from December 2001 to February 2003. Adult
      patients with intra-abdominal infections requiring surgery were randomized to
      receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4
      divided doses. The primary analysis of efficacy was the clinical response rate in
      clinically and microbiologically evaluable patients at the test-of-cure
      assessment 2 weeks after completion of therapy. All treated patients were
      included in the safety analysis. Patient demographics, disease characteristics,
      and treatment duration in both treatment groups were generally similar. The most
      commonly isolated pathogens at baseline were E coli (greater than 50% of cases in
      each group) and B fragilis ( approximately 9%). Favorable clinical response rates
      were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for
      piperacillin/tazobactam recipients. The frequencies of drug-related adverse
      events, most commonly diarrhea and elevated serum alanine aminotransferase
      levels, were similar in both treatment groups. Six of 180 ertapenem recipients
      (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug
      related adverse experiences. In this study, ertapenem and piperacillin/tazobactam
      were comparably safe and effective treatments for adult patients with complicated
      intra-abdominal infections.

PMID- 16627224
TI  - Surgery is justified in patients with bowel obstruction due to radiation therapy.
AB  - The management of the patient with radiation-induced bowel obstruction remains
      controversial. To reassess the surgical therapy for radiation-induced bowel
      obstruction, we analyzed 22 patients operated upon at the National Taiwan
      University Hospital. In 10 patients, peritoneal carcinomatosis was found during
      operation. We classified them as "recurrence group" and the remaining 12 patients
      as the "study group." Three patients in the study group had metastases, which did
      not cause bowel obstruction. The clinical presentation and image findings of both
      groups were not significantly different. The patients of the study group tended
      to have a low body mass index (mean +/- SD, 18.7 +/- 1.92 kg/m(2)) and decreased
      serum albumin level (mean +/- SD, 3.12 +/- 0.32 g/dl). Total parenteral nutrition
      was given for 27.1 +/- 16.0 days (mean +/- SD). The strategies of operation
      included resection and anastomosis (nine patients), bypass (two patients), or
      ileostomy (one patient). Operation resolved bowel obstruction and enteral
      nutrition was resumed in all the patients postoperatively. No early postoperative
      mortality occurred. Four patients had morbidity, including one reoperation
      because of anastomotic failure, one enterovesical fistula, and two cases of wound
      infection. The estimated median survival time of the study group (21 months) was
      significantly longer than that of the recurrence group (5 months). Specifically
      in the patients without previous neoplasm recurrence or metastasis, overall
      survival was 100%, 80%, and 53%, at 1, 2, and 5 years after surgery,
      respectively. We conclude surgery plays a role in both diagnostic and therapeutic
      aspects of radiation bowel injury. For selected patients, resection and primary
      anastomosis is an appropriate choice.

PMID- 16627225
TI  - Spontaneous mesenteric hemorrhage associated with Ehlers-Danlos syndrome.
AB  - The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective
      tissue and is frequently associated with catastrophic arterial complications. Its
      surgical treatment is extremely difficult because of the fragility of vessels.
      This article describes three patients with vascular type of Ehlers-Danlos
      syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture.
      The clinical and molecular characteristics of the disease are briefly reviewed.

PMID- 16627226
TI  - Postprandial augmentation of absorption of water and electrolytes in jejunum is
      neurally modulated: implications for segmental small bowel transplantation.
AB  - Postprandial augmentation of absorption of water and electrolytes is believed to
      occur in the jejunum. Neural mechanisms of control, however, have not been
      studied in the in situ jejunum or in the transplanted bowel. The aim of this
      study was to determine if postprandial augmentation of absorption occurs in the
      in situ jejunum and to evaluate neural mechanisms controlling postprandial
      jejunal absorption. Based on our previous work, we hypothesized that postprandial
      augmentation of absorption does not occur in the jejunum in situ and that
      extrinsic denervation of the jejunum is associated with decreased postprandial
      absorption. Absorption was studied in an 80 cm, in situ jejunal segment in six
      dogs by using an isosmolar electrolyte solution alone, or with 80 mmol/L glucose
      before and after jejunal transection to disrupt intrinsic neural continuity of
      the study segment with the remaining gut. Net absorptive fluxes of water and
      electrolytes were measured in the fasted state and after a 400-kcal meal. Another
      six dogs were studied 3 weeks after our validated model of extrinsic denervation
      of jejunoileum; identical fasting and postprandial absorptive states were
      evaluated. Postprandial augmentation of absorption of water and electrolytes did
      occur in the jejunum (P < 0.03) both in the absence and in the presence of
      intraluminal glucose. After intrinsic neural transection or extrinsic
      denervation, no postprandial augmentation of absorption occurred, with or without
      glucose. Postprandial augmentation of absorption of water and electrolytes occurs
      in the in situ jejunum. Disrupting intrinsic neural continuity or extrinsic
      denervation (as after intestinal transplantation) abolishes postprandial
      augmentation.

PMID- 16627227
TI  - Visuospatial abilities correlate with performance of senior endoscopy specialist
      in simulated colonoscopy.
AB  - Visuospatial abilities have been demonstrated to predict the performance of
      medical students in simulated endoscopy. However, little has been reported
      whether differences in visuospatial abilities influence the performance of senior
      endoscopists or whether their vast endoscopy experience reduces the importance of
      these abilities. Eleven senior endoscopists were included in our study. Before
      the simulated endoscopies in GI Mentor II (gastroscopy: case 3, module 1 and
      colonoscopy: case 3, module 1), the endoscopists performed three visuospatial
      tests: (1) pictorial surface orientation (PicSOr), (2) card rotation, and (3)
      cube comparison tests that monitor the ability of the tested person to re-create
      a three-dimensional image from a two-dimensional presentation as well as mentally
      manipulate that re-created image. The results of the visuospatial tests were
      correlated to the performance parameters of the virtual-reality endoscopy
      simulator. The percent of time spent with clear view in the simulated colonoscopy
      correlated well with the performance in the visuospatial PicSOr (r = -0.75, P =
      0.01), card rotation (r = 0.75, P = 0.01), and cube comparison (r = 0.79, P =
      0.004) tests. The endoscopists who performed better in the visuospatial tests
      also were better at maintaining visualization of the colon lumen. Those who
      performed better in the PicSOr test formed fewer loops during colonoscopy (r =
      0.60, P = 0.05). In the technically less demanding simulated gastroscopy, there
      were no such correlations. The visuospatial tests performed better in
      endoscopists not playing computer games. Good visuospatial ability correlates
      significantly with the performance of experienced endoscopists in a technically
      demanding simulated colonoscopy, but not in the less demanding simulated
      gastroscopy.

PMID- 16627228
TI  - Chronic pouchitis after ileal pouch-anal anastomosis for ulcerative colitis:
      effect on quality of life.
AB  - Chronic pouchitis can be observed in up to 30% of patients after proctocolectomy
      with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). It remains
      a poorly understood complication and often requires chronic antibiotic and
      antidiarrheal treatment. We hypothesized that its occurrence can be predicted by
      distinct clinical parameters and that it adversely affects quality of life. Sixty
      eight of 129 consecutive UC patients who underwent IPAA over a 10-year period
      were evaluated by Cleveland Clinic Global Quality of Life questionnaires,
      telephone interviews, and by chart review. Using bivariate comparison, clinical
      predictors for the occurrence of chronic pouchitis were sought, and postoperative
      data analyzed with regard to functional results and quality of life. Nineteen of
      68 patients (28%) experienced chronic pouchitis, but its occurrence could not be
      predicted by any variable assessed. Patients with chronic pouchitis complained of
      more frequent fecal incontinence (32% vs. 4% in controls; P < 0.01), of more
      frequent bowel movements (7.7/day vs. 6.2/day; P < 0.05), and experienced severe
      abdominal pain more often (P < 0.05). Overall quality of life and satisfaction
      with surgery, as well as subjective health and energy levels were lower in
      patients with chronic pouchitis (P < 0.01); however, greater than 80% of these
      patients would consider undergoing the same procedure again.

PMID- 16627229
TI  - Pancreaticoduodenectomy: superior mesenteric artery first approach.

PMID- 16627230
TI  - Management of common bile duct stones.

PMID- 16627231
TI  - Foregut duplication cyst of the stomach.

PMID- 16627232
TI  - "Identification and management of an errant antiperistaltic roux limb after total
      gastrectomy".

PMID- 16627236
TI  - Advanced MRI could help to differentiate meningeal carcinomatosis with mass
      effect from cerebral metastasis in prostate cancer.
AB  - Prostatic neoplasms are the second cause of mortality due to cancer in men. Brain
      metastases are a rare presentation, whereas epidural localizations are relatively
      frequent. However both occur late in the evolution of the cancer. Thus a
      reliable, fast and non-invasive diagnosis would be useful in this setting.
      Regarding the prognosis of such disease, earlier treatment may probably influence
      the quality of life and postpone fatal evolution. However improved survival is
      more hypothetical. We report the case of a 69-year old man with a hormone
      refractory adenocarcinomatous prostatic cancer presenting with diffuse
      intracranial metastases. An MRI analysis using T2 perfusion images, diffusion
      weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps excluded
      intra-axial brain metastases and concluded to the existence of voluminous nodular
      dural metastases. We discuss the imaging techniques and review literature of
      neurological complications of prostate cancer.

PMID- 16627238
TI  - [Epigenetics and cancer].
AB  - The term epigenetics encompasses all the modifications that are stable across
      cell generations, but which do not imply any change in DNA sequence. Post
      translational modifications of the histones and DNA methylation are the most
      studied types of epigenetic information due to their major impact on
      transcription. The link between epigenetics and cancer arises from the fact that
      epigenetic deregulations frequently participate in tumorigenesis by inactivation
      of tumour-suppressor genes. Since these deregulations are reversible, hopes of
      treatment rely on a better understanding of the maintenance mechanisms of the
      epigenetic information. Among the different pathways of transcription inhibition,
      DNA methylation is the simplest and one of the best characterized at the present
      time. Inhibitors of DNA methyltransferases are currently under clinical trials
      and already show promising results.

PMID- 16627239
TI  - [HIF-1 activation during tumor progression: implications and consequences].
AB  - The transcription factor hypoxia-inducible factor 1 (HIF-1) regulates the
      expression of more than 70 genes in response to hypoxic stress. Composed of two
      subunits, HIF-1 activity is modulated by the availability of the HIF-1alpha
      protein subunit. The stability and transcriptional activity of this extremely
      labile protein is affected by post-translational modifications. Hypoxia and non
      hypoxic stimuli allow the formation of an active HIF-1 complex in many types of
      human cancers. However, the exact implication of HIF-1 activation in tumor
      progression is still not precisely understood. The HIF-1 dependent genic products
      are involved in tumoral angiogenesis, in the metabolic switch to anaerobic
      glycolysis and in prosurvival, proliferative and apoptotic mechanisms. In this
      review, we will focus on the hypoxic and non-hypoxic stimuli leading to HIF-1
      activation and in its implication in tumor processes. We will highlight the most
      recent developments in molecular and cellular signaling that are upstream and
      downstream of HIF-1.

PMID- 16627240
TI  - [Stakes, aims and specificities of the physician-patient communication in cancer
      care: state of the art and perspectives].
AB  - The physician-patient relationship has three main stakes : creating a high
      quality inter-personal relationship, exchanging information and decision-making.
      The achievement of these stakes implies that the physician and the patient are
      able to reach specific communicational objectives. The aim of this paper is to
      review the characteristics of care as regards cancer patients that could prevent
      the physician from reaching these stakes and objectives. Moreover, two future
      perspectives in this field are exposed : the study of factors that influence the
      communication process when a cancer patient is accompanied by one of his or her
      relative in a medical interview and the study of personal characteristics of
      physicians that can predict their ability to communicate in cancer care. On the
      basis of this triple review, proposals aimed to improve physician-patient
      communication in cancer care are exposed.

PMID- 16627241
TI  - [Smoking cessation interventions among cancer patients].
AB  - What are the benefits of smoking cessation for cancer patients ? Are they
      motivated to quit smoking ? Which interventions are currently proposed to these
      patients ? Our literature review emphasizes the risks linked with continued
      smoking (increased relapse risk, increased second cancer risk...) as well as the
      abstinence benefits. Some studies have even identified differences in quality of
      life between smoker and non-smoker cancer patients. Research works also show that
      cancer patients desire to quit smoking and expect to receive some help to do so.
      But only a limited number of smoking cessation programs are specifically devoted
      to those persons. Moreover, the few studies that have evaluated the efficacy of
      those programs generally contain important methodological bias. In the future, it
      will then be imperative to explore the smoking cessation benefits in terms of
      quality of life but also to set up smoking cessation programs and to accurately
      assess their efficacy.

PMID- 16627242
TI  - [Improvement in breast cancer survival between 1975 and 2003 in a cohort of 5722
      women].
AB  - To evaluate improvement in breast cancer management between 1975 and 2003, we
      constituted a cohort of 5722 women with an invasive non-metastatic breast cancer.
      An active follow-up was carried out and completed using administrative databases.
      Survival rates were computed using a classical person-time and a period analyses.
      Relative survival rates were also presented. Advanced cancers at diagnosis
      decreased from 70.7% to 45.5% between 1975 and 2003. Person-time analysis showed
      a 48.8% reduction in death rates over 30 years. Survival at 10 years ranged from
      50% (CI95% = 45-55) for women diagnosed in 1975-1979 to 66% (CI95% = 63-69) for
      those diagnosed in 1990-1994. Using period analysis, we estimated the 10 year
      survival of women diagnosed in 2000-2003 to be 68% (CI95% = 64-72). Overall
      relative survival was 76% (CI95% = 71-80) at 10 years. Taking into account known
      prognosis factors, survival was significantly improved for recent diagnosis
      periods (p<0.00001). Observed improvement in survival confirmed 'in real life'
      data from clinical trials.

PMID- 16627243
TI  - [Endometrial cancer by laparoscopy and vaginal approach in the obese patient].
AB  - To prove feasibility of laparoscopic and vaginal surgical approach in obese
      patients with endometrial cancer, 81 patients were included retrospectively in 2
      Cancer Centres : 41 obese and 40 non obese. We performed hysterectomy with
      oophorectomy and pelvic lymphadenectomy by laparoscopic and vaginal approach.
      Operative time was higher for obese patients vs non obese (150 vs 121 minutes, p
      = 0.01) but pelvic nodes (16.3 vs 16.2), postoperative stay (3.8 [2-8] vs 3.6
      days [2-7]), complications and disease-free survival (93 % vs 83 %) were similar.
      Matching 41 obese patients treated by laparoscopy with 29 obese patients with
      endometrial cancer treated by laparotomy, hospital stay was shorter in the
      laparoscopic group (3.8 [2-8] vs 7.4 days [5-10] p < 0.001) and pelvic nodes
      (16.3 [3-50] vs 11.5 [2-34]), operative time (149.9 [80-300] vs 167.9 minutes [60
      390]) and disease-free survival (93 vs 80 %) were similar. One patient treated by
      laparotomy never received intended radiotherapy because of a delay greater than 3
      months caused by cutaneous necrosis. For obese patients with stage I endometrial
      adenocarcinoma, laparoscopic approach should be first choice because of similar
      operative complications and pelvic nodes, shorter hospital stay and less
      abdominal wall morbidity associated with lower risk to delay adjuvant
      radiotherapy.

PMID- 16627244
TI  - [Accepting chemotherapy at the age of 70 and over: between autonomy and ageing].
AB  - This study is based on the interview of 21 subjects, aged 70 years and over,
      attending an oncology centre. At the end of their treatment, we have explored the
      processes of patient's choice, including goals, resources and constraints. The
      main variables influencing the acceptance of chemotherapy are full awareness of
      one's clinical condition, irrespective of whether a cure is possible or not, self
      perceived state of health, and lastly life expectancy. Age itself initially does
      not appear to be a limiting factor. Every effort should be made to tailor
      communication to individual needs, not least because of a link between learned
      and perceived treatment adverse effects. We found that symptoms, especially
      fatigue, hamper routine activities, leading to social withdrawal. Gradually the
      manifestations of the disease itself and of its treatment, combined with age,
      reveal both personal vulnerability and the role of support networks.

PMID- 16627245
TI  - [Sentinel lymph node biopsy for breast cancer after neoadjuvant chemotherapy:
      influence of nodal status before treatment].
AB  - OBJECTIVES: To determine feasibility and accuracy of SLN biopsy in locally
      advanced breast cancer treated by neoadjuvant chemotherapy. MATERIALS AND
      METHODS: From April 2001 to December 2004, a prospective series was constituted
      of 74 women with invasive breast carcinoma T1T2T3N0N1 receiving neoadjuvant
      chemotherapy. The SLN located was removed using subdermal periareolar injection
      of radiolabelled nanocolloid and axillary lymph node dissection was
      systematically performed. RESULTS: A SLN was identified in 68/74 (92%) patients.
      It was metastatic in 30/68 cases (44%). The false negative (FN) rate was 14%
      (5/35). In the subgroup of 42 patients clinically N(0) before chemotherapy,
      accuracy was 100 %, and FN rate 0%, in the 32 N1, accuracy was 83%, and FN rate
      25%. CONCLUSIONS: SLN biopsy using a single subdermal injection of radiolabelled
      nanocolloid in patients with a breast cancer treated by neoadjuvant chemotherapy
      is technically feasible and appears to be highly accurate in the subgroup of
      patients with a clinically negative axilla breast cancer before treatment.

PMID- 16627246
TI  - [New intra-operative probes for sentinel lymph node dissection].

PMID- 16627247
TI  - Detection of alpha-thalassemia in beta-thalassemia carriers and prevention of Hb
      Bart's hydrops fetalis through prenatal screening.
AB  - The aim of this study was to detect alpha-thalassemia in beta-thalassemia
      carriers during prenatal screening. During a 12-year prenatal screening program,
      a total of 158 couples (3.2%) were diagnosed to be the discordant alpha- and beta
      thalassemia carriers. Of the 158 beta-thalassemia partners, seven (4.4%) were
      found to have co-inheritance of alpha0-thalassemia, and three (1.9%) found to
      have co-inheritance of alpha(+)-thalassemia. Three pregnancies affected with Hb
      Bart's hydrops fetalis were terminated in the 158 couples. The results showed
      that molecular analysis must be used for accurate diagnosis of double
      heterozygotes in couples presumed to be discordant for alpha- and beta
      thalassemia on hematologic testing.

PMID- 16627248
TI  - Minimal residual disease analysis in children with t(12;21)-positive acute
      lymphoblastic leukemia: comparison of Ig/TCR rearrangements and the genomic
      fusion gene.
AB  - Quantification of minimal residual disease (MRD) based on clonotypic
      immunoglobulin/ T-cell receptor (Ig/TCR) gene rearrangements is widely used as an
      independent prognostic parameter in childhood acute lymphoblastic leukemia (ALL).
      In this study we compared MRD by quantification of Ig/TCR targets and genomic
      ETV6-RUNX1 specific sequences. In ten of twelve patients with t(12;21)+ ALL we
      observed concordance with rapid blast reduction in nine, and high-level
      persistence in one case. The two remaining patients showed low-level persistence
      of the genomic breakpoint specific sequence. These patients have remained in
      complete remission for 38 and 41 months, so far, indicating that a small ETV6
      RUNX1-positive clone is not detrimental to the short-term prognosis of affected
      children.

PMID- 16627249
TI  - Mutations of AML1 in non-M0 acute myeloid leukemia: six novel mutations and a
      high incidence of cooperative events in a South-east Asian population.
AB  - Point mutations of AML1 are uncommon and predominantly reported in a rare
      minimally differentiated acute myeloid leukemia (M0 AML). Few data exist
      regarding the frequency of AML1 mutations in non-M0 cases. We screened 284
      consecutive adult Thai patients with de novo AML and found that 3.9% had AML1
      mutations. The highest incidence occurred in M6. Six novel mutations were
      uniquely identified in non-M0 cases. Sixty-four percent of the non-M0 patients
      with AML1 mutations had coexisting genetic abnormalities including FLT3 mutation
      in 36%. Our study provides evidence to support the model of multiple co-operating
      events, which could also be critical in the development of leukemia in non-M0 AML
      patients with mutated AML1. The prognostic significance of these novel mutations
      remains to be determined.

PMID- 16627250
TI  - Mutations in telomerase catalytic protein in Japanese children with aplastic
      anemia.
AB  - Recent studies indicate that a subset of patients with apparently acquired
      aplastic anemia (AA) have mutations in genes for telomerase ribonucleoprotein
      complex components. We looked for mutations in telomerase RNA (TERC) and
      telomerase reverse transcriptase (TERT) in 96 Japanese children with acquired AA
      and in 76 healthy controls. No mutations in TERC were found in any subjects.
      Novel heterozygous, non-synonymous mutations in TERT (T726M and G682D) were found
      in two patients with AA, neither of whom had clinical characteristics suggesting
      constitutional AA. This genetic difference does not explain the higher incidence
      of AA in Asian populations.

PMID- 16627251
TI  - A comparison of donor lymphocyte infusions or imatinib mesylate for patients with
      chronic myelogenous leukemia who have relapsed after allogeneic stem cell
      transplantation.
AB  - Imatinib mesylate is highly effective in relapsed chronic myelogenous leukemia
      (CML) after allogeneic hematopoetic stem cell transplantation (HSCT). However, it
      is unknown whether imatinib produces durable molecular remissions. The outcome of
      CML patients transplanted at our center who had received only imatinib for
      relapse after HSCT was compared with that of patients treated with donor
      lymphocyte infusions (DLI). Imatinib therapy resulted in a higher incidence of
      relapse and inferior leukemia-free survival (p=0.006 and p=0.016, respectively).
      These data suggest that imatinib alone probably does not cure relapse after HSCT.

PMID- 16627252
TI  - Short-term effect of miglustat in every day clinical use in treatment-naive or
      previously treated patients with type 1 Gaucher's disease.
AB  - In a prospective, open-label study, 25 patients with mild-to-moderate type 1
      Gaucher's disease (GD1) were treated with miglustat (Zavesca), an oral
      glucosylceramide synthase inhibitor, over 12 months. Of the 25 patients, 10 were
      therapy-naive and 15 had previously received enzyme replacement therapy (ERT).
      Clinical status, blood parameters, biomarkers, and organomegaly were assessed at
      baseline at 6 months and at 12 months. At 6 months the previously untreated
      patients showed a mean increase in hemoglobin of 0.77 g/dL, platelet counts
      improved or remaining stable, chitotriosidase and CCL18 decreased. These results
      were similar to those observed in 40 Spanish GD1 patients on ERT. Bone marrow
      infiltration cleared at 12 months. In the previously treated group, clinical and
      hematologic parameters and biomarkers were maintained/ improved at 12 months.
      Miglustat was well tolerated. The efficacy of miglustat treatment after 6 months
      was comparable to that of ERT.

PMID- 16627253
TI  - Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in
      patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study.
AB  - BACKGROUND AND OBJECTIVES: Although alkylating agents are clearly beneficial in
      multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic
      progenitor cells usually precludes their use as front-line therapy in patients
      scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the
      impact of first-line chemotherapy with alkylating agents on stem cell collection
      in MM patients. DESIGN AND METHODS: Seven hundred and eighty-nine patients
      included in the Spanish multicenter protocol GEM-2000 underwent mobilization
      therapy after four courses of alternating VBMCP/VBAD chemotherapy. RESULTS: The
      mobilization regimens consisted of standard or high-dose granulocyte colony
      stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in
      206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388
      patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%).
      Multivariate analysis indicated that advanced age (p<0.0001) and longer interval
      between diagnosis and mobilization (p=0.012) were the two variables associated
      with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were
      not observed between the mobilization regimens. Of the 789 patients included in
      the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did
      not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9)
      neutrophils/L could be recovered after 11 days (median time; range, 5-71 days)
      and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6
      69 days). INTERPRETATION AND CONCLUSIONS: A short-course of therapy with
      alkylating agents according to the GEM-2000 protocol was associated with an
      appropriate CD34+ cell collection, and allowed the planned ASCT to be performed
      in the majority of MM patients.

PMID- 16627254
TI  - Comparison of allele specific oligonucleotide-polymerase chain reaction and
      direct sequencing for high throughput screening of ABL kinase domain mutations in
      chronic myeloid leukemia resistant to imatinib.
AB  - To identify a fast and sensitive method for screening for mutations in patients
      with imatinib- resistant chronic myeloid leukemia (CML), we compared allele
      specific oligonucleotide- polymerase chain reaction (ASO-PCR) assay with
      conventional direct sequencing. Among the 68 imatinib resistant CML patients
      studied, 18 amino acid substitutions were detected in 44 patients by two assays.
      The sensitivity of ASO-PCR was superior to that of direct sequencing as it could
      detect one mutant allele in 100 approximately 100,000 wild type sequences. The
      fastness, simplicity, and sensitivity of ASO-PCR assays will be useful for
      routine monitoring of mutations, especially for frequently identified mutations.

PMID- 16627255
TI  - The significance of minimal residual disease kinetics in adults with newly
      diagnosed PML-RARalpha-positive acute promyelocytic leukemia: results of a
      prospective trial.
AB  - Seventy adults with acute promyelocytic leukemia were studied to clarify the
      significance of the level and kinetics of minimal residual disease (MRD) over
      their entire treatment course by realtime quantitative polymerase chain reaction.
      At a median follow-up of 44 months, nine relapses had occurred. The 5-year
      probabilities of relapse and disease-free survival were 17.3+/-5.4% and 81.5+/
      5.4%, respectively. A MRD level of >10-3 after first consolidation was the most
      powerful predictor of relapse (85.7+/-13.2% versus 7.3+/-4.1%, p<0.001) and
      disease-free survival (14.3+/-13.2% versus 91.2%+/-4.3%, p<0.001). Prospective
      MRD monitoring may allow us to identify subgroups of patients at high risk of
      relapse earlier during treatment.

PMID- 16627256
TI  - The involvement of stromal derived factor 1alpha in homing and progression of
      multiple myeloma in the 5TMM model.
AB  - BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a lethal plasma cell cancer
      characterized by the monoclonal growth of cells in the bone marrow. To reach the
      bone marrow, MM cells need to be attracted by chemokines. Recently, it has been
      shown that chemokines can also be involved in the growth of several cancer types.
      Stromal cell derived factor 1a (SDF1alpha) or CXCL12 is known to play an
      important role as a chemokine for hematopoietic progenitor cells and human MM
      cells. We studied the effects of SDF1a in the 5TMM murine model. DESIGN AND
      METHODS: The in vitro effects of SDF1alpha were analyzed by gelatin zymography,
      adhesion, migration, proliferation, and chemoinvasion assays and by blockade with
      the CXCR4 inhibitor, 4F-benzoyl-TN14003. In vivo, diseased mice were treated with
      either vehicle or 4F-benzoyl-TN14003. RESULTS: In vitro SDF1alpha was capable of
      attracting both 5T2MM and 5T33MM cells and inducing a 1.6-fold increase in MMP9
      production by the 5TMM cells, which was correlated with an increased invasive
      capacity. In addition, SDF1alpha induced a 20% increase in DNA synthesis in the
      5TMM cells. All these effects could be blocked by the CXCR4 inhibitor, 4Fbenzoyl-
      TN14003. An in vivo study in the 5T33MM model showed that blocking CXCR4 led to a
      20% reduction in bone marrow tumor load. INTERPRETATION AND CONCLUSIONS: These
      data demonstrate that SDF1alpha/CXCR4 is involved in the homing and the expansion
      of MM cells. Blocking CXCR4 could be useful in synergy with other anti-neoplastic
      treatments targeting the bone marrow microenvironment.

PMID- 16627257
TI  - The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for
      both arterial and venous thrombosis in patients with systemic lupus
      erythematosus.
AB  - In an effort to clarify the clinical significance of anti-phospholipid antibodies
      (aPL) detected by enzyme-linked immunosorbent assay (ELISA), we examined the
      prevalence of anti-cardiolipin antibodies (aCL), anti-beta2-glycoprotein I
      antibodies (anti-beta2-GPI), antiprothrombin antibodies (anti-PT), and anti
      phosphatidylserine/prothrombin antibodies (anti-PS/PT) in 175 patients with
      systemic lupus erythematosus (SLE) comprising 67 patients with thrombotic
      complications. The present study showed that positive results of anti-beta2-GPI
      ELISA and anti-PS/PT-ELISA could serve as markers of thrombotic complications in
      patients with SLE, whereas aCL and anti-PT are less reliable as markers of these
      complications. Furthermore, results of the anti-PS/PT-ELISA correlate best with
      the occurrence of both arterial and venous thrombosis in patients with SLE.

PMID- 16627258
TI  - Immunoglobulin light chain gene rearrangements in precursor-B-acute lymphoblastic
      leukemia: characteristics and applicability for the detection of minimal residual
      disease.
AB  - We analyzed the frequency and characteristics of Vk-Jk and Vlambda-Jlambda
      rearrangements inpatients with precursor-B-acute lymphoblastic leukemia (ALL) and
      evaluated the applicability of these rearrangements as targets for minimal
      residual disease (MRD) detection. Using the BIOMED-2 primer sets, Vk-Jk and
      Vlambda-Jlambda rearrangements were detected in 30% and 17% of patients,
      respectively. Vk-Jk rearrangements were particularly frequent in common-ALL,
      children between 5-10 years, and TEL-AML1-positive patients. Vk-Jk and Vlambda
      Jlambda rearrangements showed a good stability between diagnosis and relapse and
      reached good sensitivities in real-time quantitative polymerase chain reaction
      analysis. Our data show that Vk-Jk and Vlambda-Jlambda rearrangements can be
      successfully applied for MRD detection in a subset of patients with precursor-B
      ALL.

PMID- 16627259
TI  - CD8+ lymphomatoid papulosis and its differential diagnosis.
AB  - We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary
      cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30
      positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP)
      based on the clinical course, which was recurrent asymptomatic papular nodular
      lesions over years responding to methotrexate; granulomatous inflammation and
      lack of other inflammatory cell elements were characteristic. In 1 case, an
      initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell
      lymphoma. The fifth case in this series was first interpreted as representing
      primary cutaneous anaplastic large cell lymphoma but was later recategorized as
      primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma owing
      to the extent of extracutaneous dissemination, including testicular involvement
      and disease progression despite chemotherapeutic intervention. Although all cases
      of LyP showed sharp cytoplasmic membrane staining with perinuclear Golgi
      accentuation with CD30, the recategorized case of aggressive epidermotropic CD8
      cytotoxic T-cell lymphoma manifested only a weak cytoplasmic staining pattern.
      CD8 LyP defines a distinctive entity with characteristic light microscopic and
      phenotypic findings and has a predilection for young males. CD30 expression can
      occur in other forms of CD8 lymphoproliferative disease unrelated to primary
      cutaneous anaplastic large cell lymphoma or LyP.

PMID- 16627260
TI  - Altered expression, localization, and phosphorylation of epithelial junctional
      proteins in celiac disease.
AB  - We aimed to study the expression and localization of the molecular components of
      enterocyte junctions in celiac disease together with the level of tyrosine
      phosphorylation, a phenomenon known to affect their cellular distribution and
      function, and to explore the influence of proinflammatory cytokines. Duodenal
      biopsy specimens from patients with celiac disease and control subjects were used
      for immunoprecipitation, immunoblotting, and immunolocalization by using
      antioccludin, anti-zonula occludens (ZO)-1, anti-E-cadherin, anti-beta-catenin,
      and antiphosphotyrosine antibodies. The same procedures were carried out on
      filter-grown Caco-2 cells incubated in the absence or presence of interferon g
      and tumor necrosis factor a. In active celiac disease, the absence of a
      phosphorylated ZO-1 and the extensive phosphorylation of beta-catenin might be
      responsible for the absence of membranous localization of occludin and E
      cadherin, respectively. The in vitro system showed an influence of the cytokines
      on the assembly of these complexes that proved the opposite to celiac samples as
      far as tight junctions were concerned because the presence of a phosphorylated ZO
      1 enables occludin to localize in the membrane.

PMID- 16627261
TI  - Vascular endothelial growth factor expression in the basal subtype of breast
      carcinoma.
AB  - The recognition of subtypes of breast carcinomas based on their molecular
      features has brought new perspectives in breast cancer research. Some key
      regulators of angiogenesis and tumor infiltration were evaluated in breast
      carcinomas of basal phenotype (cytokeratin [CK]5+). Immunohistochemical analysis
      with 14 primary antibodies was performed in 100 formalin-fixed, paraffin-embedded
      samples of invasive ductal carcinomas. CK5 correlated with indicators of poor
      outcome, including precocious age, high histologic grade, lymph node positivity,
      advanced pathologic stage, negativity for hormonal receptors, and a high
      proliferative rate (Ki-67 labeling index). CK5 also correlated with vascular
      endothelial growth factor (VEGF) expression but not with the microvessel density.
      Considering that VEGF-overexpressing neoplastic mammary cells display increased
      proliferative activity in vitro regardless of the angiogenic effect of VEGF, the
      differential expression of VEGF might contribute to the more aggressive behavior
      of these neoplasms. CK5 correlated with tissue inhibitor of metalloproteinase
      (TIMP)-1, but not matrix metalloproteinase (MMP)-1, MMP-2, extracellular matrix
      metalloproteinase inducer, TIMP-2 or plasminogen activator inhibitor, indicating
      that antiproteolytic stimuli might be preponderant in these neoplasms.

PMID- 16627262
TI  - Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular
      carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver.
AB  - The cytoplasmic staining of thyroid transcription factor (TTF)-1 was analyzed in
      86 liver resection specimens, including 40 hepatocellular carcinoma (HCC), 4
      metastatic HCC, 20 cholangiocarcinoma, 2 combined hepatocellular
      cholangiocarcinoma (CHC), and 20 metastatic carcinoma (MC) specimens with
      immunohistochemical stains to TTF-1, cytokeratin (CK)19, hepatocyte paraffin 1,
      alpha-fetoprotein, polyclonal carcinoembryonic antigen, CK7, and CK20. TTF-1
      cytoplasmic staining was identified in 93% of HCCs (37/40), 100% of metastatic
      HCCs (4/4), 10% of cholangiocarcinomas (2/20), and 5% of MCs (1/20). CK19 was
      positive in all cholangiocarcinomas and MCs but only in 5% of HCCs (2/40) and
      none of the metastatic HCCs (0/4). TTF-1 cytoplasmic staining positively
      correlates with differentiation and the trabecular growth pattern of HCC. The
      results suggest TTF-1 cytoplasmic staining, together with CK19, might serve as a
      useful marker for the diagnosis of primary and metastatic HCC and for the
      differential diagnosis of HCC from cholangiocarcinoma and MC. The mechanism of
      TTF-1 cytoplasmic staining is explored.

PMID- 16627263
TI  - Double slide viewing as a cytology quality improvement initiative.
AB  - Few studies have measured the effect of pre-sign out double viewing of cytology
      cases as a means to decrease error. Three Agency for Healthcare Research and
      Quality-funded project sites performed pre-sign out double viewing of 431
      pulmonary cytology cases. Two-step or more differences in diagnosis were
      arbitrated as interpretive errors, and the effect of double viewing was measured
      by comparing the frequency of cytologic-histologic correlation-detected errors in
      the previous 2 years with the double-viewing period. The number of interpretive
      errors detected by double viewing for the 3 institutions was 2.7%, 0% and 1.9%,
      respectively. Double viewing did not lower the frequency of cytologic-histologic
      correlation false-negative errors. We conclude that double viewing detects errors
      in up to 1 of every 37 cases and that biases in the double-viewing process limit
      error detection.

PMID- 16627264
TI  - Abnormal beta-catenin and reduced axin expression are associated with poor
      differentiation and progression in non-small cell lung cancer.
AB  - We studied the expression of axin and beta-catenin and their relation to
      clinicopathologic factors in 100 non-small cell lung cancers (NSCLCs) by
      immunohistochemical analysis. The mutation in exon 3 of the beta-catenin gene was
      examined by polymerase chain reaction and direct sequencing. Preserved axin
      expression was significantly higher in well- and moderately differentiated NSCLC
      samples than in poorly differentiated ones. Reduced membranous expression of beta
      catenin was shown in 80 cases, whereas 26 cases had aberrant nuclear expression.
      Poor differentiation and lymph node metastasis were associated significantly with
      reduced beta-catenin expression. Lower axin expression was related significantly
      to higher nuclear beta-catenin expression. However, this study failed to detect
      any exon 3 mutation in the beta-catenin gene in the 100 NSCLC samples. We
      conclude that reduced beta-catenin and axin expression might predict poor
      differentiation in NSCLC. Reduced axin expression, but not mutation in exon 3,
      might be an important explanation for the abnormal beta-catenin expression in
      NSCLC.

PMID- 16627265
TI  - Thymoma classification: current status and future trends.
AB  - The classification of thymic epithelial neoplasms has been a controversial topic
      for many years. Recent advances in diagnostic methods and renewed interest in the
      biology of these tumors has led to efforts by investigators to shed new light on
      their biologic behavior and to offer novel perspectives on these unusual
      neoplasms. Several new classification schemes have been proposed, including the
      new World Health Organization schema for the histologic typing of tumors of the
      thymus. We review the current status of thymoma classification and comment on
      problem areas and future trends that may offer a more pragmatic approach to these
      tumors.

PMID- 16627266
TI  - Osteosarcoma: anatomic and histologic variants.
AB  - Osteosarcoma is the most common primary tumor of bone, yet its absolute incidence
      among malignant tumors is low. Within its strict histologic definition,
      osteosarcoma comprises a family of lesions with considerable diversity in
      histologic features and grade. Its prognosis is dependent not only on these
      parameters, but also on its anatomic site. It may occur inside the bones (in the
      intramedullary or intracortical compartment), on the surfaces of bones, and in
      extraosseous sites. Information of diagnostic or prognostic significance has not
      been elucidated from studies of its cytogenetics. This review summarizes the
      anatomic and histologic variations of osteosarcoma and offers a schema for its
      subclassification.

PMID- 16627267
TI  - Detection and identification of cytochrome P-450 2C9 alleles *1, *2, and *3 by
      high-resolution melting curve analysis of PCR amplicons.
AB  - High-resolution melting curve analysis using a fluorescent DNA binding dye can
      detect sequence variations in a closed-tube system without labeled primers or
      probes. We developed and verified a melting analysis assay for common single
      nucleotide polymorphisms of cytochrome P-450 (CYP) 2C9 that affect warfarin
      metabolism. We used this method to genotype 84 patients receiving warfarin. For
      wild-type, *1/*1, 50% fluorescence corresponded to a mean+/-SD of 87.17+/-0.05
      degrees C, whereas *2/*2 was 0.4 degrees C lower. The *1/*2 melting curve was
      easily distinguished from *1/*1 and *2/*2 based on transition temperature and
      shape. Exon 7 showed a more complex melting curve; however, genotypes *1/*1,
      *1/*3, and *3/*3 were easily distinguishable. Melting curves were highly
      reproducible (SD of temperature for multiple fluorescence values 0.04 degrees C
      0.11 degrees C; mean, 0.06 degrees C). Heterozygotes (*1/*2 or *1/*3) required
      significantly lower mean maintenance warfarin doses compared with wild-type
      (30.67 and 29.56 vs 42.81 mg/wk; P<.05). High-resolution melting analysis
      provides a simple and accurate method for genotyping of CYP2C9.

PMID- 16627268
TI  - Rituximab can be combined with daily plasma exchange to achieve effective B-cell
      depletion and clinical improvement in acute autoimmune TTP.
AB  - Much of idiopathic thrombotic thrombocytopenic purpura (TTP) is attributed to the
      presence of an autoantibody to ADAMTS13, the metalloprotease that degrades
      ultralarge von Willebrand protein multimers. Most patients respond to treatment
      with therapeutic plasma exchange (TPE), which replaces the missing protease and
      removes the circulating inhibitor. However, a substantial fraction of idiopathic
      TTP cases (10%-20%) might not respond to TPE alone, and, therefore, interest has
      been gathering around the use of the novel immunosuppressive anti-B-cell
      antibody, rituximab. We report 2 cases of refractory TTP in which the combined
      use of plasma exchange and rituximab was associated with clinical resolution of
      active TTP, and we discuss the benefits and possible timing of combined therapy.

PMID- 16627269
TI  - The correlation dimension identifies B-cell immunoglobulin light chain
      restriction in peripheral blood flow cytometry data.
AB  - The correlation dimension (D2) is a mathematical tool that quantifies dimensional
      properties of fractals. We set out to determine whether immunoglobulin light
      chain restriction (LCR) in B-cell lymphoproliferative disorders (BCLPDs) could be
      identified using the D2. The D2 was calculated from flow cytometry data files
      (FCS 2.0) from a training set of peripheral blood specimens from 22 patients with
      and 23 patients without BCLPD. A cutoff value derived from the training set was
      applied to a validation set of 69 patients with and 64 patients without BCLPD. In
      the training set, all BCLPDs had a D2 of less than 0.72 (CD19-gated kappa-lambda
      data). When this cutoff was applied to the validation set, the D2 had sensitivity
      and specificity values of 88% and 98%, respectively. The D2 can identify LCR in
      peripheral blood flow cytometry data. It offers operator-independent data
      analysis and may be useful in objectively quantifying differences in data
      distribution.

PMID- 16627270
TI  - Spurious hemoglobin Barts caused by bilirubin: a common interference mimicking an
      uncommon hemoglobinopathy.
AB  - High-performance liquid chromatography (HPLC) is replacing electrophoresis for
      identification of hemoglobin variants. Our objective was to identify unknown tall
      peaks with elution times and shapes of hemoglobin Barts found on hemoglobin
      chromatograms that could not be confirmed by alkaline and acid gel
      electrophoresis. Of 90 specimens identified with this peak, 86 were from patients
      with hemoglobin SS. Regression of the height of the unknown peaks to serum
      bilirubin concentrations, diminution of the unknown peaks by washing the
      specimens, and chromatographic similarity of a total bilirubin serum calibrator,
      a bilirubin proficiency testing specimen, and 3 patients' serum samples with
      markedly elevated bilirubin to hemoglobin Barts provide evidence the peak was
      bilirubin. We suggest exclusion of bilirubin before HPLC results are reported as
      consistent with hemoglobin Barts.

PMID- 16627271
TI  - Immunohistochemical analysis identifies two cyclin D1+ subsets of plasma cell
      myeloma, each associated with favorable survival.
AB  - The significance of cyclin D1 expression in plasma cell myeloma was examined by
      immunohistochemical analysis using a newly available rabbit monoclonal antibody
      with superior staining properties. Two patterns of positive staining were
      observed, each associated with distinct pathologic features. Strong cyclin D1
      staining was associated with increased plasma cells at diagnosis (P=.026),
      lymphoplasmacytic morphologic features (P=.029), CD20 expression (P=.040), and
      t(11;14)(q13;q32) as detected by interphase fluorescence in situ hybridization
      with simultaneous CD138 immunofluorescence (P<.001). In contrast, weak staining
      was associated with hyperdiploidy (P=.02) and gains of the CCND1 locus (P=.01).
      Overall survival was longer in the cyclin D1+ cases than in cyclin D1- cases
      (estimated 3-year survival, 73% vs 27%; P=.005). Improved survival was seen in
      the strongly positive and weakly positive groups compared with cyclin D1- cases
      (P=.005). This report shows for the first time that cyclin D1 immunohistochemical
      analysis can provide prognostic information in plasma cell myeloma.

PMID- 16627272
TI  - Identification of the JAK2 V617F mutation in chronic myeloproliferative disorders
      using FRET probes and melting curve analysis.
AB  - We developed and validated a real-time polymerase chain reaction assay using
      fluorescent hybridization probes and melting curve analysis to identify the JAK2
      V617F mutation, which is implicated in a substantial proportion of chronic
      myeloproliferative disorders (CMPDs). DNA from 161 samples was isolated from
      peripheral blood granulocytes and formalin-fixed bone marrow clot sections in
      patients with CMPDs and without myeloproliferative disorders previously genotyped
      for the JAK2 V617F (G-->T) mutation, which included 114 wild types (GG) and 47
      mutants (GT and TT). Melting curve analysis of these samples yielded 114 wild
      types, 42 heterozygotes, and 5 homozygotes showing 100% concordance. Analytic
      sensitivity of the assay for mutant DNA was 5% for the LightTyper (Roche Applied
      Sciences, Indianapolis, IN) and 10% for the LightCycler (Roche Applied Sciences).
      Consistent with earlier reports, 78% of the non-chronic myelogenous leukemia CMPD
      patients and 8% of non-CMPD patients displayed this mutation. This study
      demonstrates that clinical genotyping of the JAK2 V617F mutation can be performed
      by melting analysis using both freshly isolated and formalin-fixed tissues.

PMID- 16627273
TI  - Paedocypris, a new genus of Southeast Asian cyprinid fish with a remarkable
      sexual dimorphism, comprises the world's smallest vertebrate.
AB  - Paedocypris is a new genus of paedomorphic cyprinid fish from highly acidic
      blackwater peat swamps in Southeast Asia. It includes two new species, one of
      which (Paedocypris progenetica) appears to be the smallest fish and vertebrate
      known, with the smallest mature female measuring a mere 7.9 mm. Paedocypris has
      many 'larval' features typically associated with paedomorphic fish (e.g. narrow
      frontals that leave the brain unprotected dorsally by bone and a precaudal larval
      fin-fold), but, uniquely among fishes, males also possess highly modified pelvic
      fins with hypertrophied muscles and a keratinized pad in front of the pelvic
      girdle, which, we hypothesize, function together as a clasping or holding device,
      thereby suggesting an unusual reproductive mode. Unfortunately, habitat
      destruction jeopardizes the survival of these fishes and thus opportunities for
      further research.

PMID- 16627274
TI  - Alternative male reproductive tactics and the immunocompetence handicap in the
      Azorean rock-pool blenny, Parablennius parvicornis.
AB  - In the Azorean rock-pool blenny (Parablennius parvicornis) reproductively active
      males display alternative morphotypes, which differ in the expression of
      secondary sexual characters (SSC). Males expressing SSC, the M+ morphotype, have
      high androgen levels and compete for crevices that will be visited by females to
      spawn. M+ males holding nests court females and care for the eggs. Males with low
      expression of SSC, the M- morphotype, have low levels of androgens and reproduce
      by stealing fertilizations from the M+ males. Based on the hypothesis that
      androgens are immunosuppressive, we expected these morphotypes to differ in
      immunocompetence. To test this hypothesis, we conducted a field study in which we
      collected repeated blood samples to monitor leukocyte populations (blood smears),
      and to measure the primary antibody response of males that were experimentally
      challenged with a foreign non-pathogenic antigen (sheep red blood cells).
      Circulating levels of 11-ketotestosterone and testosterone were higher in M+
      males than in M- males. Neither granulocyte nor thrombocyte counts did covariate
      with androgens or male tactic. In contrast, lymphocyte counts and humoral
      antibody response were negatively correlated with body size, and as expected,
      both were lower in M+ than in M- males. Interestingly, in M+ males androgen
      levels decreased after immunization, and this was less in nest-holder males than
      in M+ males that were floating around in the pools. Within each morphotype we
      found no relationship between androgens and immunocompetence. The latter result
      is not supportive for androgen regulated immunosuppression in M+ males. A
      possible alternative is enhancement of immunity in M- males. These males had
      relatively high levels of injuries in comparison with M+ males. High immunity
      might be a consequence of high infection rate because of such injuries.

PMID- 16627275
TI  - Strong assortative mating between allopatric sticklebacks as a by-product of
      adaptation to different environments.
AB  - Speciation involves the evolution of reproductive isolation between populations.
      One potentially important mechanism is the evolution of pre- or postzygotic
      isolation between populations as a by-product of adaptation to different
      environments. In this paper, we tested for assortative mating between allopatric
      stickleback populations adapted to different ecological niches. Our experimental
      design controlled for interpopulation interactions and non-adaptive explanations
      for assortative mating. We found that prezygotic isolation was surprisingly
      strong: when given a choice, the majority of matings occurred between individuals
      from similar environments. Our results indicate that the by-product mechanism is
      a potent source of reproductive isolation, and likely contributed to the origin
      of sympatric species of sticklebacks.

PMID- 16627276
TI  - Evidence for adaptive male mate choice in the fruit fly Drosophila melanogaster.
AB  - Theory predicts that males will benefit when they bias their mating effort
      towards females of higher reproductive potential, and that this discrimination
      will increase as males become more resource limited. We conducted a series of
      experiments to test these predictions in a laboratory population of the fruitfly,
      Drosophila melanogaster. In this species, courtship and copulation have
      significant costs to males, and females vary greatly in fecundity, which is
      positively associated with body size. When given a simultaneous choice between
      small and large virgin females, males preferentially mated with larger, more
      fecund, females. Moreover, after males had recently mated they showed a stronger
      preference for larger females. These results suggest that male D. melanogaster
      adaptively allocate their mating effort in response to variation in female
      quality and provide some of the first support for the theoretical prediction that
      male stringency in mate choice increases as resources become more limiting.

PMID- 16627277
TI  - Outbreeding selects for spiteful cytoplasmic elements.
AB  - In addition to their nuclear genome, the vast majority of eukaryotes harbour
      cytoplasmic genomes, e.g. in mitochondria or chloroplasts. In the majority of
      cases, these cytoplasmic genomes are transmitted maternally only, leading to
      selective pressures divergent from those that act on nuclear genes. In
      particular, cytoplasmic genes, which reduce the fitness of males that carry them,
      but have no fitness effect in females, are believed to be selectively neutral.
      Here, we go a step further and argue that in outbreeding populations (i.e.
      populations with inbreeding avoidance), 'spiteful' cytoplasmic elements that
      reduce the number of offspring produced by males are in fact selected for. We
      study this process by means of a stochastic model, analysing both the probability
      of spread and the impact that such a spiteful cytotype can have on population
      dynamics. Our results demonstrate that the probability of spread of the spiteful
      cytotype can be several times higher in outbreeding than in panmictic
      populations. Spread and fixation of the spiteful cytotype can lead to different
      qualitative effects on the population dynamics, including extinction, decreased
      or increased stable population size. We discuss our results in respect to
      cytoplasmically induced male infertility and cytoplasmic incompatibility.

PMID- 16627278
TI  - Phenotypic plasticity in the scaling of avian basal metabolic rate.
AB  - Many birds exhibit short-term, reversible adjustments in basal metabolic rate
      (BMR), but the overall contribution of phenotypic plasticity to avian metabolic
      diversity remains unclear. The available BMR data include estimates from birds
      living in natural environments and captive-raised birds in more homogenous,
      artificial environments. All previous analyses of interspecific variation in BMR
      have pooled these data. We hypothesized that phenotypic plasticity is an
      important contributor to interspecific variation in avian BMR, and that captive
      raised populations exhibit general differences in BMR compared to wild-caught
      populations. We tested this hypothesis by fitting general linear models to BMR
      data for 231 bird species, using the generalized least-squares approach to
      correct for phylogenetic relatedness when necessary. The scaling exponent
      relating BMR to body mass in captive-raised birds (0.670) was significantly
      shallower than in wild-caught birds (0.744). The differences in metabolic scaling
      between captive-raised and wild-caught birds persisted when migratory tendency
      and habitat aridity were controlled for. Our results reveal that phenotypic
      plasticity is a major contributor to avian interspecific metabolic variation. The
      finding that metabolic scaling in birds is partly determined by environmental
      factors provides further support for models that predict variation in scaling
      exponents, such as the allometric cascade model.

PMID- 16627279
TI  - No extension of lifespan by ablation of germ line in Drosophila.
AB  - Increased reproduction is frequently associated with a reduction in longevity in
      a variety of organisms. Traditional explanations of this 'cost of reproduction'
      suggest that trade-offs between reproduction and longevity should be obligate.
      However, it is possible to uncouple the two traits in model organisms. Recently,
      it has been suggested that reproduction and longevity are linked by molecular
      signals produced by specific reproductive tissues. For example, in Caenorhabditis
      elegans, lifespan is extended in worms that lack a proliferating germ line, but
      which possess somatic gonad tissue, suggesting that these tissues are the sources
      of signals that mediate lifespan. In this study, we tested for evidence of such
      gonadal signals in Drosophila melanogaster. We ablated the germ line using two
      maternal effect mutations: germ cell-less and tudor. Both mutations result in
      flies that lack a proliferating germ line but that possess a somatic gonad. In
      contrast to the findings from C. elegans, we found that germ line ablated females
      had reduced longevity relative to controls and that the removal of the germ line
      led to an over-proliferation of the somatic stem cells in the germarium. Our
      results contrast with the widely held view that it is downstream reproductive
      processes such as the production and/or laying of eggs that are costly to
      females. In males, germ line ablation caused either no difference, or a slight
      extension, in longevity relative to controls. Our results indicate that early
      acting, upstream reproductive enabling processes are likely to be important in
      determining reproductive costs. In addition, we suggest that the specific roles
      and putative patterns of molecular signalling in the germ line and somatic
      tissues are not conserved between flies and worms.

PMID- 16627280
TI  - Red dominates black: agonistic signalling among head morphs in the colour
      polymorphic Gouldian finch.
AB  - Recent sexual selection studies on the evolution of bird colouration have mainly
      focused on signals with a high level of condition-dependent variation, with much
      less attention given to colour traits whose expression is genetically controlled.
      Here, we experimentally tested the relative importance of a genetic colour
      polymorphism in determining male dominance in the Gouldian finch (Erythrura
      gouldiae), a species displaying three completely discrete but naturally co
      occurring genetically inherited phenotypes; yellow-, red- (carotenoid) and black
      headed (melanin) morphs. First, in staged dominance contests between unfamiliar
      birds of different head morphs, red-headed males dominated black-headed males,
      both of which dominated the yellow-headed birds. Second, within morphs, the
      intensity and size of the strongly ultraviolet-blue collar determined the outcome
      of these contests, and among the red-headed males, redder males dominated less
      chromatic birds. Lastly, when the dominance signal of red-headed birds was
      experimentally destabilized (i.e. blackened or reddened), naturally red-headed
      morphs continued to dominate both the black-and yellow-headed morphs. Together,
      these results suggest that intrinsic dominance-related behavioural differences
      between the three colour morphs, which are likely to influence the relative
      fitness of each morph, contribute to the complex selective patterns maintaining
      these three discrete phenotypes in relatively stable frequencies in wild
      populations.

PMID- 16627281
TI  - Symmetrical crypsis and asymmetrical signalling in the cuttlefish Sepia
      officinalis.
AB  - The salience of bilateral symmetry to humans has led to the suggestion that
      camouflage may be enhanced in asymmetrical patterns. However, the importance of
      bilateral symmetry in visual signals (and overall morphology) may constrain the
      evolution of asymmetrical camouflage, resulting in the bilaterally symmetrical
      cryptic patterns that we see throughout the animal kingdom. This study
      investigates the cuttlefish (Sepia officinalis), which can control the degree of
      symmetry in its coloration. Ten juvenile S. officinalis were filmed in two
      behavioural contexts (cryptic and threatened) to test the prediction that cryptic
      patterns will be expressed more asymmetrically than an anti-predator signal known
      as the 'deimatic display'. Cryptic body patterns, particularly those with a
      disruptive function, were found to exhibit a high degree of bilateral symmetry.
      By contrast, the components of the deimatic display were often expressed
      asymmetrically. These results are contrary to the predicted use of symmetry in
      defensive coloration, indicating that the role of symmetry in both crypsis and
      visual signalling is not as straightforward as previously suggested.

PMID- 16627282
TI  - The effects of floral mimics and models on each others' fitness.
AB  - Plants that lack floral rewards may nevertheless attract pollinators by mimicking
      the flowers of rewarding plants. It has been suggested that both mimics and
      models should suffer reduced fitness when mimics are abundant relative to their
      models. By manipulating the relative densities of an orchid mimic Disa nivea and
      its rewarding model Zaluzianskya microsiphon in small experimental patches within
      a larger population we demonstrated that the mimic does indeed suffer reduced
      pollination success when locally common relative to its model. Behavioural
      experiments suggest that this phenomenon results from the tendency of the long
      proboscid fly pollinator to avoid visits to neighbouring plants when encountering
      the mimic. No negative effect of the mimic on the pollination success of the
      model was detected. We propose that changes in pollinator flight behaviour,
      rather than pollinator conditioning, are likely to account for negative frequency
      dependent reproductive success in deceptive orchids.

PMID- 16627283
TI  - Diverse staghorn corals (Acropora) in high-latitude Eocene assemblages:
      implications for the evolution of modern diversity patterns of reef corals.
AB  - Acropora is the most diverse genus of reef-building corals in the world today. It
      occurs in all three major oceans; it is restricted to latitudes 31 degrees N-31
      degrees S, where most coral reefs occur, and reaches greatest diversity in the
      central Indo-Pacific. As an exemplar genus, the long-term history of Acropora has
      implications for the evolution and origins of present day biodiversity patterns
      of reef corals and for predicting their response to future climate change.
      Diversification of Acropora was thought to have occurred in the central Indo
      Pacific within the previous two million years. We examined Eocene fossils from
      southern England and northern France and found evidence that precursors of up to
      nine of 20 currently recognized Acropora species groups existed 49-34 Myr, at
      palaeolatitudes far higher than current limits, to 51 degrees N. We propose that
      pre-existing diversity contributed to later rapid speciation in this important
      functional group of corals.

PMID- 16627284
TI  - Coevolution of slow-fast populations: evolutionary sliding, evolutionary pseudo
      equilibria and complex Red Queen dynamics.
AB  - We study the interplay of ecological and evolutionary dynamics in communities
      composed of populations with contrasting time-scales. In such communities,
      genetic variation of individual traits can cause population transitions between
      stationary and cyclic ecological regimes, hence abrupt variations in fitness.
      Such abrupt variations raise ridges in the adaptive landscape, where the
      populations are poised between equilibrium and cyclic coexistence and along which
      evolutionary trajectories can remain sliding for long times or halt at special
      points called evolutionary pseudo-equilibria. These novel phenomena should be
      generic to all systems in which ecological interactions cause fitness to vary
      discontinuously. They are demonstrated by the analysis of a predator-prey
      community, with one adaptive trait for each population. The eco-evolutionary
      dynamics of the system show a number of other distinctive features, including
      evolutionary extinction and two forms of Red Queen dynamics. One of them is
      characterized by intermittent bouts of cyclic oscillations of the two
      populations.

PMID- 16627285
TI  - Ecological divergence promotes the evolution of cryptic reproductive isolation.
AB  - Speciation can involve the evolution of 'cryptic' reproductive isolation that
      occurs after copulation but before hybrid offspring are produced. Because such
      cryptic barriers to gene exchange involve post-mating sexual interactions,
      analyses of their evolution have focused on sexual conflict or traditional sexual
      selection. Here, we show that ecological divergence between populations of
      herbivorous walking sticks is integral to the evolution of cryptic reproductive
      isolation. Low female fitness following between-population mating can reduce gene
      exchange between populations, thus acting as a form of cryptic isolation. Female
      walking sticks show reduced oviposition rate and lower lifetime fecundity
      following between-population versus within-population mating, but only for mating
      between populations using different host-plant species. Our results indicate that
      even inherently sexual forms of reproductive isolation can evolve as a by-product
      of ecological divergence and that post-mating sexual interactions do not
      necessarily evolve independently of the ecological environment.

PMID- 16627286
TI  - Phylogenetic and ecological determinants of the neotropical dawn chorus.
AB  - The concentration of avian song at first light (i.e. the dawn chorus) is widely
      appreciated, but has an enigmatic functional significance. One widely accepted
      explanation is that birds are active at dawn, but light levels are not yet
      adequate for foraging. In forest communities, the onset to singing should thus be
      predictable from the species' foraging strata, which is ultimately related to
      ambient light level. To test this, we collected data from a tropical forest of
      Ecuador involving 57 species from 27 families of birds. Time of first song was a
      repeatable, species-specific trait, and the majority of resident birds, including
      non-passerines, sang in the dawn chorus. For passerine birds, foraging height was
      the best predictor of time of first song, with canopy birds singing earlier than
      birds foraging closer to the forest floor. A weak and opposite result was
      observed for non-passerines. For passerine birds, eye size also predicted time of
      first song, with larger eyed birds singing earlier, after controlling for body
      mass, taxonomic group and foraging height. This is the first comparative study of
      the dawn chorus in the Neotropics, and it provides the first evidence for
      foraging strata as the primary determinant of scheduling participation in the
      dawn chorus of birds.

PMID- 16627287
TI  - Marsupials from space: fluctuating asymmetry, geographical information systems
      and animal conservation.
AB  - We report the development of a new quantitative method of assessing the effects
      of anthropogenic impacts on living beings; this method allows us to assess actual
      impacts and to travel backwards in time to assess impacts. In this method, we
      have crossed data on fluctuating asymmetry (FA, a measure of environmental or
      genetic stress), using Didelphis albiventris as a model, with geographical
      information systems data relating to environmental composition. Our results show
      that more impacted environments resulted in statistically higher levels of FA.
      Our method appears to be a useful and flexible conservation tool for assessing
      anthropogenic impacts.

PMID- 16627288
TI  - What's in it for me? Self-regard precludes altruism and spite in chimpanzees.
AB  - Sensitivity to fairness may influence whether individuals choose to engage in
      acts that are mutually beneficial, selfish, altruistic, or spiteful. In a series
      of three experiments, chimpanzees (Pan troglodytes) could pull a rope to access
      out-of-reach food while concomitantly pulling another piece of food further away.
      In the first study, they could make a choice that solely benefited themselves
      (selfishness), or both themselves and another chimpanzee (mutualism). In the next
      two experiments, they could choose between providing food solely for another
      chimpanzee (altruism), or for neither while preventing the other chimpanzee from
      receiving a benefit (spite). The main result across all studies was that
      chimpanzees made their choices based solely on personal gain, with no regard for
      the outcomes of a conspecific. These results raise questions about the origins of
      human cooperative behaviour.

PMID- 16627289
TI  - Parasites as causative agents of human affective disorders? The impact of anti
      psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's
      ability to alter host behaviour.
AB  - With increasing pressure to understand transmissible agents, renewed recognition
      of infectious causation of both acute and chronic diseases is occurring.
      Epidemiological and neuropathological studies indicate that some cases of
      schizophrenia may be associated with environmental factors, such as exposure to
      the ubiquitous protozoan Toxoplasma gondii. Reasons for this include T. gondii's
      ability to establish persistent infection within the central nervous system, its
      ability to manipulate intermediate host behaviour, the occurrence of neurological
      and psychiatric symptoms in some infected individuals, and an association between
      infection with increased incidence of schizophrenia. Moreover, several of the
      medications used to treat schizophrenia and other psychiatric disease have
      recently been demonstrated in vitro to possess anti-parasitic, and in particular
      anti-T. gondii, properties. Our aim here was thus to test the hypothesis that the
      anti-psychotic and mood stabilizing activity of some medications may be achieved,
      or at least augmented, through their in vivo inhibition of T. gondii replication
      and invasion in infected individuals. In particular we predicted, using the
      epidemiologically and clinically applicable rat-T. gondii model system, and
      following a previously described and neurologically characterized 'feline
      attraction' protocol that haloperidol (an anti-psychotic used in the treatment of
      mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer
      used in the treatment of mental illnesses including schizophrenia), would be, at
      least, as effective in preventing the development of T. gondii-associated
      behavioural and cognitive alterations as the standard anti-T. gondii
      chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while T.
      gondii appears to alter the rats' perception of predation risk turning their
      innate aversion into a 'suicidal' feline attraction, anti-psychotic drugs prove
      as efficient as anti-T. gondii drugs in preventing such behavioural alterations.
      Our results have important implications regarding the aetiology and treatment of
      such disorders.

PMID- 16627290
TI  - Temperature-dependent transmission and latency of Holospora undulata, a
      micronucleus-specific parasite of the ciliate Paramecium caudatum.
AB  - Transmission of parasites to new hosts crucially depends on the timing of
      production of transmission stages and their capacity to start an infection. These
      parameters may be influenced by genetic factors, but also by the environment. We
      tested the effects of temperature and host genotype on infection probability and
      latency in experimental populations of the ciliate Paramecium caudatum, after
      exposure to infectious forms of its bacterial parasite Holospora undulata.
      Temperature had a significant effect on the expression of genetic variation for
      transmission and maintenance of infection. Overall, low temperature (10 degrees
      C) increased levels of (multiple) infection, but arrested parasite development;
      higher temperatures (23 and 30 degrees C) accelerated the onset of production of
      infectious forms, but limited transmission success. Viability of infectious forms
      declined rapidly at 23 and 30 degrees C, thereby narrowing the time window for
      transmission. Thus, environmental conditions can generate trade-offs between
      transmission relevant parameters and alter levels of multiple infection or
      parasite-mediated selection, which may affect evolutionary trajectories of
      parasite life history or virulence.

PMID- 16627293
TI  - Streptomyces inside-out: a new perspective on the bacteria that provide us with
      antibiotics.
AB  - Many of the antibiotics used today are made by a group of bacteria called
      Streptomyces. Streptomycetes evolved about 450 million years ago as branched
      filamentous organisms adapted to the utilization of plant remains. They reproduce
      by sending up specialized aerial branches, which form spores. Aerial growth is
      parasitic on the primary colony, which is digested and reused for aerial growth.
      The reproductive phase is coordinated with the secretion of antibiotics, which
      may protect the colony against invading bacteria during aerial growth. A clue to
      the integration of antibiotic production and aerial growth is provided by bldA
      mutants, which are defective in both processes. These mutants lack the ability to
      translate a particularly rare codon, UUA, in the genetic code. The UUA codon (TTA
      in DNA) is present in several regulatory genes that control sets of antibiotic
      production genes, and in one, bldH that controls aerial mycelium formation. The
      regulatory genes for antibiotic production are all involved in self-reinforcing
      regulatory systems that potentially amplify the regulatory significance of small
      changes in the efficiency of translation of UUA codons. One of the regulatory
      targets of bldH is an extracellular protease inhibitor protein that is likely to
      delay the digestion of the primary biomass until the colony is ready for aerial
      growth. The use of the UUA codon to orchestrate different aspects of
      extracellular biology appeared very early in Streptomyces evolution.

PMID- 16627294
TI  - Stratospheric ozone depletion.
AB  - Solar ultraviolet radiation creates an ozone layer in the atmosphere which in
      turn completely absorbs the most energetic fraction of this radiation. This
      process both warms the air, creating the stratosphere between 15 and 50 km
      altitude, and protects the biological activities at the Earth's surface from this
      damaging radiation. In the last half-century, the chemical mechanisms operating
      within the ozone layer have been shown to include very efficient catalytic chain
      reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX
      and ClOX chains involve the emission at Earth's surface of stable molecules in
      very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere
      for as long as a century before absorbing ultraviolet radiation and decomposing
      to create NO and Cl in the middle of the stratospheric ozone layer. The growing
      emissions of synthetic chlorofluorocarbon molecules cause a significant
      diminution in the ozone content of the stratosphere, with the result that more
      solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This
      ozone loss occurs in the temperate zone latitudes in all seasons, and especially
      drastically since the early 1980s in the south polar springtime-the 'Antarctic
      ozone hole'. The chemical reactions causing this ozone depletion are primarily
      based on atomic Cl and ClO, the product of its reaction with ozone. The further
      manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the
      1987 Montreal Protocol of the United Nations. Atmospheric measurements have
      confirmed that the Protocol has been very successful in reducing further
      emissions of these molecules. Recovery of the stratosphere to the ozone
      conditions of the 1950s will occur slowly over the rest of the twenty-first
      century because of the long lifetime of the precursor molecules.

PMID- 16627292
TI  - Adventures in vascular biology: a tale of two mediators.
AB  - I would like to thank the Royal Society for inviting me to deliver the Croonian
      Lecture. In so doing, the Society is adding my name to a list of very
      distinguished scientists who, since 1738, have preceded me in this task. This is,
      indeed, a great honour. For most of my research career my main interest has been
      the understanding of the normal functioning of the blood vessel wall and the way
      this is affected in pathology. During this time, our knowledge of these subjects
      has grown to such an extent that many people now believe that the conquering of
      vascular disease is a real possibility in the foreseeable future. My lecture
      concerns the discovery of two substances, prostacyclin and nitric oxide. I would
      like to describe the moments of insight and some of the critical experiments that
      contributed significantly to the uncovering of their roles in vascular biology.
      The process was often adventurous, hence the title of this lecture. It is the
      excitement of the adventure that I would like to convey in the text that follows.

PMID- 16627295
TI  - The multiple-channel cochlear implant: the interface between sound and the
      central nervous system for hearing, speech, and language in deaf people-a
      personal perspective.
AB  - The multiple-channel cochlear implant is the first sensori-neural prosthesis to
      effectively and safely bring electronic technology into a direct physiological
      relation with the central nervous system and human consciousness, and to give
      speech perception to severely-profoundly deaf people and spoken language to
      children. Research showed that the place and temporal coding of sound frequencies
      could be partly replicated by multiple-channel stimulation of the auditory nerve.
      This required safety studies on how to prevent the effects to the cochlea of
      trauma, electrical stimuli, biomaterials and middle ear infection. The mechanical
      properties of an array and mode of stimulation for the place coding of speech
      frequencies were determined. A fully implantable receiver-stimulator was
      developed, as well as the procedures for the clinical assessment of deaf people,
      and the surgical placement of the device. The perception of electrically coded
      sounds was determined, and a speech processing strategy discovered that enabled
      late-deafened adults to comprehend running speech. The brain processing systems
      for patterns of electrical stimuli reproducing speech were elucidated. The
      research was developed industrially, and improvements in speech processing made
      through presenting additional speech frequencies by place coding. Finally, the
      importance of the multiple-channel cochlear implant for early deafened children
      was established.

PMID- 16627296
TI  - New ways of preventing HIV infection: thinking simply, simply thinking.
AB  - HIV infection is the greatest health crisis in human history. It continues to
      spread unchecked among the poor in the developing world because we have failed to
      design simple preventative methods that are available and affordable to those
      living on under Dollars 2 a day. Five new methods are discussed. (i) A natural
      microbicide. Intravaginal lime or lemon juice has been used for centuries as a
      traditional contraceptive. The juice can also kill HIV in the laboratory, but
      clinical trials are needed to see if vaginal application is acceptable, safe and
      effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian
      immunodeficiency virus (SIV) infection by keratinizing the vagina with topical
      oestrogen. If women take the oral contraceptive pill vaginally it retains its
      contraceptive efficacy, and the oestrogen it contains should thicken the vagina
      and protect against HIV infection. Clinical trials are needed. (iii) Male
      circumcision. Removal of the inner foreskin removes the main site of HIV entry
      into the penis, resulting in a sevenfold reduction in susceptibility to
      infection. The practice needs to be promoted. (iv) Post-coital penile hygiene.
      Wiping the penis immediately after intercourse with lime or lemon juice or
      vinegar should kill the virus before it has had a chance to infect. A clinical
      trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing
      countries to photograph their impressions of HIV/AIDS is a powerful way of
      getting them to discuss the subject openly, and develop their own preventative
      strategies.

PMID- 16627297
TI  - Ovulation, pregnancy, placentation and husbandry in the African elephant
      (Loxodonta africana).
AB  - The African elephant reproduces so efficiently in the wild that overpopulation is
      now a serious problem in some game parks in Zimbabwe, Botswana and South Africa.
      The female reaches puberty between 10 and 12 years of age in the wild and, when
      in captivity, shows oestrous cycles of 14-15 weeks duration. She readily
      conceives a singleton in the wild yet her uterus has the capacity for twins. She
      shows a gestation length of 22 months and, in the wild, shows a population
      density and feed dependent intercalving interval of 4-8 years. The trophoblast
      erodes the lumenal epithelium of the endometrium and stimulates upgrowths of
      blood vessel-containing stromal villi, which develop eventually into the broad,
      tightly folded lamellae of the zonary, endotheliochorial placenta. Significant
      quantities of leaked maternal erythrocytes and ferric iron are phagocytosed by
      specialized trophoblast cells in the haemophagous zones at the lateral edges of
      the placental band. Although the placenta itself is endocrinologically inert, the
      foetal gonads, which enlarge greatly during the second half of pregnancy can
      synthesize 5alpha-dihydryoprogesterone and other 5alpha pregnane derivatives from
      cholesterol and pregnenolone. These products may synergize with progestagens
      secreted by the 2-8 large corpora lutea which are always present in the maternal
      ovaries throughout gestation to maintain the pregnancy state.

PMID- 16627298
TI  - Indigenous petrol sniffing: lessons from a coronial inquest.

PMID- 16627299
TI  - The rise of Viagra among British illicit drug users: 5-year survey data.
AB  - Viagra use among British nightclubbers, a sentinel population of illicit drug
      users, was first reported in 1999. There has since been little attention paid to
      the evolution of patterns of non-prescribed use, apart from among men who have
      sex with men. Beginning in 1999 an annual survey has been conducted with a
      specialist dance music magazine, permitting cross-sectional comparisons over
      time. Rising levels of lifetime and current use prevalence and data on patterns
      of both male and female use are reported, along with elevated prevalence levels
      among both gay men and women. Experimentation with Viagra appears increasingly to
      have become established among British nightclubbers who use recreational drugs.
      Ethnographic and epidemiological study and monitoring of adverse consequences is
      now needed to fully appreciate reasons for use and the extent of possible harms.

PMID- 16627300
TI  - Patients receiving a prescription for diamorphine (heroin) in the United Kingdom.
AB  - The United Kingdom is unusual internationally in that it is one of few countries
      able to prescribe diamorphine for the treatment of opiate dependence. Prescribing
      diamorphine has been part of the UK response to drug problems since the 1920s.
      Despite this, little is known about who receives diamorphine and how treatment is
      delivered. This study aims to describe the characteristics and treatment regimes
      of opiate-dependent drug users receiving a prescription for diamorphine in the
      United Kingdom in 2000, and report on their status in 2002. A retrospective case
      note review was conducted in England and Wales. Two hundred and ten (72%;
      210/292) patients' sets of case-notes were reviewed at 27 of the 42 (64%) drug
      clinics where diamorphine was prescribed by the doctor. Patients had been
      receiving a prescription for diamorphine for a median length of six years. The
      majority were unemployed white males, with a median age of 44 years. Illicit drug
      use and criminal activity, while low, had not been eliminated totally. The
      majority were prescribed ampoules and few had significant health problems. In
      some cases patients had been transferred to injectable diamorphine from
      injectable methadone to reduce injection related problems. There were wide
      variations in dose. The majority of patients had no serious drug, health or
      social problems. Diamorphine prescribing was a long-term commitment. The
      experience from the United Kingdom has been one of long-term prescribing with the
      aim of retaining patients in treatment and reducing the harms caused by illicit
      drug use. Prospective studies are needed to determine the long-term consequences
      of receiving a diamorphine prescription.

PMID- 16627301
TI  - Abstinence-orientated buprenorphine replacement therapy for young adults in out
      patient counselling.
AB  - This study assessed treatment retention, compliance and completion of a 9-month
      buprenorphine replacement programme. In addition, changes in drug use and other
      relevant variables, as well as predictors of completion, were examined. Seventy
      five opioid-dependent out-patients (mean age 26 years; 33% females) who aimed for
      opioid abstinence were enrolled into the study. Assessments were undertaken prior
      to buprenorphine induction and again at 3, 6 and 9 months. Forty patients (53%)
      completed the buprenorphine programme. At 9 months, 67 patients (87%) were still
      in counselling. Mean attendance rates for buprenorphine dosing and counselling
      sessions were 0.91 and 0.74, respectively. There were significant and persistent
      reductions in drug use during treatment with, however, a reversed tendency in the
      9th month. Psychiatric problems escalated at 9 months, and three patients died
      during the detoxification phase. Completion was predicted by fewer previous
      treatment episodes. Detoxification from buprenorphine is associated with
      substantial psychological distress and an increased death risk. Buprenorphine
      replacement therapy should be continued until the patient chooses to leave, and
      close monitoring during the detoxification phase is essential.

PMID- 16627302
TI  - Estimating prevalence of injecting drug use: a comparison of multiplier and
      capture-recapture methods in cities in England and Russia.
AB  - We consider the question of what method should be recommended to estimate the
      prevalence of injecting drug use (IDU); and compare multiplier and capture
      recapture (CRC) methods of estimating prevalence of injecting drug use (IDU). The
      prevalence of injecting drug use in four cities (Brighton, Liverpool, London and
      Togliatti) was estimated using similar methods: covariate capture-recapture (CRC)
      and multipliers. The multipliers, generated either from a community recruited
      survey or historical/literature-based, were applied to a range of 'benchmarks':
      specialist drug treatment, arrests, accident and emergency department (A&E),
      syringe exchange, HIV tests and opiate overdose deaths. The CRC estimates were
      assumed to be 'preferred/gold standard' [2,304 (95% confidence interval 1,514 -
      3,737) in Brighton, 2,910 (2,546 - 4,977) in Liverpool, 16,782 (13,793 - 21,620)
      in 12 London boroughs and 15,039 (12,696 - 18,515) male IDU in Togliatti]. The
      ranges given by the multiplier estimates obtained through the community survey
      varied from 200 to 770 in Brighton, 530 to 1,300 in Liverpool, 2,900 to 10,600 in
      London and 12,400 to 91,000 in Togliatti. Several multipliers gave implausible
      results, lower than the observed data collected for another benchmark, and in the
      three English cities all these multiplier estimates were below the lower 95%
      confidence interval of the CRC estimate. In Togliatti, only one multiplier
      estimate was close to the preferred CRC estimates, with the rest implausibly
      high. The multiplier estimates based on historical/literature multipliers also
      ranged widely from 390 to 4,800 for Brighton, from 1,645 to 2,800 in Liverpool,
      from 4,650 to 12,600 in the 12 London boroughs and 12,800 to 32,000 in Togliatti.
      In the three UK cities the mortality multiplier estimates were closest to the
      capture-recapture estimates. The study was a practical demonstration comparing a
      range of multiplier estimates with a single CRC study. In almost all the
      individual comparisons the multiplier estimates performed poorly. CRC methods
      should be preferred as the means of estimating numbers of drug users with
      multiplier methods being used with caution and only where CRC is not possible.

PMID- 16627303
TI  - The association between cocaine use and short-term outcomes for the treatment of
      heroin dependence: findings from the Australian Treatment Outcome Study (ATOS).
AB  - The aim of this study was to determine the prevalence of cocaine use among
      individuals presenting for treatment for heroin dependence, describe the clinical
      profile of heroin users who also use cocaine and to establish the effects of
      cocaine use on short term outcomes for the treatment for heroin dependence. A
      longitudinal follow-up of 549 heroin users recruited in Sydney for the Australian
      Treatment Outcome Study was conducted at 3-month post-baseline interview. At
      baseline, current cocaine use was common (39%) and was associated with increased
      drug use, needle risk taking and criminality. The 3-month prevalence of cocaine
      use declined significantly to 19%. Thirty-five per cent of those who had used
      cocaine at baseline continued to use at 3 months, while 9% of the sample had
      commenced cocaine use. Those who entered residential rehabilitation at baseline
      were less likely than other treatment entrants and the non-treatment group to
      have used cocaine at follow-up. Treatment retention was not affected by baseline
      cocaine use status; however, baseline cocaine users (CU) displayed higher levels
      of heroin use, polydrug use and drug-related problems. A poorer outcome was
      associated with the commencement or continuation of cocaine use, while cessation
      of cocaine use resulted in significant improvements on these measures. Cocaine
      use was common among individuals seeking treatment for heroin dependence and was
      an important moderator of treatment outcome. It appears that cocaine use has a
      strong negative effect on treatment outcome over and above that caused by
      polydrug use generally.

PMID- 16627304
TI  - Developing an integrated substance use and mental health service in the
      specialised setting of a youth detention centre.
AB  - This article describes the frequency of co-morbid substance use and mental health
      problems of young people within the youth justice system and demonstrates that
      mental health and drug and alcohol services can be integrated and work
      effectively. The establishment of an integrated Mental Health Alcohol Tobacco and
      Other Drugs Service (MHATODS) to juveniles in detention represents a shift away
      from the traditional paradigm of separate services frequently found throughout
      Australia. The development of referral procedures and adolescent-focused
      treatment programmes that are tailored to the specific needs of this
      disadvantaged population are discussed. A wide-ranging literature review
      illustrates the consequences of the high prevalence of co-morbid substance use
      and mental health problems in juveniles within the youth justice system. A
      retrospective and descriptive account is given of the expansion of the MHATODS,
      including the recruitment of an Indigenous health worker, the incorporation of an
      automatic referral process for young people with substance use problems and the
      development of a brief four-session drug and alcohol counselling programme and a
      group relapse prevention programme. The proportion of Indigenous clients referred
      to MHATODS is now equitable to referrals of non-Indigenous youth. The
      introduction of an automatic voluntary referral process resulted in an increase
      in referrals for drug and alcohol assessment and counselling from 17% to 64% of
      total referrals. Of those young people commencing the drug and alcohol programme,
      32% completed all sessions. While young people reportedly enjoyed the group
      programme, feedback from participants indicated that they felt vulnerable in a
      group setting. MHATODS recognises the limitations of the prevailing paradigm of
      separate service delivery for mental health and drug and alcohol treatment, and
      has developed an integrated treatment service for juveniles in detention. The
      service has expanded its referral base for substance use problems by employing an
      Indigenous health worker, and initiating an automatic referral process for young
      people admitted into detention who have a history of significant substance use.
      Early evidence indicates increased utilisation of drug and alcohol services by
      young people in detention.

PMID- 16627305
TI  - A critical appraisal of the Australian comparative trial of methadone and
      buprenorphine maintenance.
AB  - While there are serious problems with the analyses and reports, the Australian
      comparative trial of methadone and buprenorphine maintenance has generated very
      useful data. Contrary to the triallists' conclusions, their study provides good
      evidence that methadone is better than buprenorphine at retaining addicts in
      programmes where clinicians can adjust their patients' daily doses. The trial
      also provides the first evidence that methadone is significantly cheaper than
      buprenorphine maintenance. The savings from less frequent clinic attendance were
      more than offset by the extra time spent dispensing buprenorphine and the greater
      cost of the buprenorphine itself. In cost-effectiveness terms, the trial's
      results show methadone 'dominates' buprenorphine as an opioid maintenance drug
      because it is not only more effective but also cheaper.

PMID- 16627306
TI  - Retention and attendance with supervised buprenorphine treatment: a case-note
      review.
AB  - Since 2001, the Langton Centre has used supervised administration of
      buprenorphine in treating heroin dependence, without distinguishing between
      detoxification and maintenance; most people commencing treatment may remain on
      buprenorphine indefinitely. The aim of this study was to describe retention in
      treatment, reasons for leaving, re-entry and pattern of attendance, and compare
      retention in practice with results from research trials, using a file review of
      sequential presentations for buprenorphine treatment. Retention in treatment was
      37% at 6 months, the same as in Australian research trials of buprenorphine
      maintenance (37%); most people dropped-out without consultation or dose tapering.
      Repeated episodes of treatment constituted 45% of all episodes; missed scheduled
      doses were common. Participation in buprenorphine treatment often involves
      repeated, short episodes and erratic attendance. Measures to improve retention in
      treatment could improve treatment efficacy.

PMID- 16627307
TI  - Treatment retention in adolescent patients treated with methadone or
      buprenorphine for opioid dependence: a file review.
AB  - The aim of this study was to compare retention and re-entry to treatment between
      adolescent subjects treated with methadone, those treated with buprenorphine, and
      those treated with symptomatic (non-opioid) medication only. We used a
      retrospective file review of all patients aged less than 18 at first presentation
      for treatment for opioid dependence. The study was conducted at the Langton
      Centre, Sydney, Australia, an agency specialising in the treatment of alcohol and
      other drug dependency. Sixty-one adolescents (age range 14 - 17 years at the time
      of commencing treatment); mean reported age of initiation of heroin use was 14 +/
      1.3 years (range 11 - 16). Sixty-one per cent were female. The first episode of
      treatment was methadone maintenance in 20 subjects, buprenorphine in 25,
      symptomatic medication in 15; one patient underwent assessment only. These 61
      subjects had a total of 112 episodes of treatment. Subjects treated with
      methadone had significantly longer retention in first treatment episode than
      subjects treated with buprenorphine (mean days 354 vs. 58, p<0.01 by Cox
      regression) and missed fewer days in the first month (mean 3 vs. 8 days, p<0.05
      by ttest). Subsequent re-entry for further treatment occurred in 25% of subjects
      treated with methadone, 60% buprenorphine and 60% symptomatic medications. Time
      to re-entry after first episode of buprenorphine treatment was significantly
      shorter than after methadone treatment (p<0.05 by Kaplan - Meier test). Methadone
      maintenance appears to have been more effective than buprenorphine at preventing
      premature drop-out from treatment of adolescent heroin users.

PMID- 16627308
TI  - Drug use and HIV/AIDS in China.
AB  - This paper on drug use and HIV/AIDS in China follows on from the column's May
      2005 article on the description of the first methadone maintenance clinic in
      Beijing. Methadone maintenance clinics and needle exchange programmes are now
      being implemented in China as a response to the rapid increase in prevalence of
      HIV/AIDS over the last 10-15 years. It is worth noting that in prior years
      methadone was available only as for short-term detoxification from opioids and
      for research purposes. Accordingly, the Department of Health Education and
      Behavioural Intervention at the National Center for AIDS Prevention and Control
      in China plans to establish 1,000 methadone replacement clinics within the next 5
      years to treat 200,000 heroin-dependent users who are at increased risk of
      HIV/AIDS. Robert Ali & Rachel HumeniukEditors, Asia Pacific ColumnThe cumulative
      number of registered drug users in mainland China increased from 70,000 in 1990
      to 1.14 million in 2004. Heroin continues to be the most commonly used drug in
      China; however, polydrug use is popular among heroin users. Sedatives/hypnotics
      (e.g. triazolam) and other uncontrolled prescription opioids (e.g. pethidine and
      tramadol) are used commonly in combination with heroin. The majority of drug
      users (79%) are young people aged between 17 and 35 years and comprise
      predominantly farmers (30%) and unemployed people (45%). The HIV/AIDS epidemic in
      China has reached expansion phase (1995-present). It is estimated that the actual
      number of HIV/AIDS cases reached 840,000, including 80,000 actual AIDS patients,
      in 2003, with injecting drug users (IDUs) making up the largest proportion of
      these cases. Although the prevalence rate of HIV/AIDS is only 0.065% in the
      Chinese population overall, there is potential for an explosive spread of
      HIV/AIDS if preventative measures are not employed. Supported by the Chinese
      government and other related international organisations, harm reduction
      strategies such as methadone maintenance treatment (MMT) and needle-syringe
      programmes (NSP) have commenced implementation to reduce the risk of HIV
      infection among heroin users.

PMID- 16627309
TI  - Drug dreams in cocaine addiction.

PMID- 16627311
TI  - Assessment of the quality of interaction in distance learning programmes
      utilizing the Internet or interactive television: perceptions of students and
      lecturers.
AB  - WebCT, a web-based virtual learning environment (VLE) and Interactive TV (ITV)
      are relatively new technologies that are used to deliver distance education at
      the Faculty of Health Sciences, Stellenbosch University. This study explores how
      effective current approaches to instructional design and interaction have been in
      utilizing these two technologies to support interaction and what lessons can be
      learnt. Five focus-group interviews were held with students and lecturers to
      assess the perceived quality of student-lecturer/student-student interactions.
      All students were invited to complete a questionnaire at the end of every module
      to assess their perceptions of interaction. Interaction was highly valued by
      students and lecturers participating in distance-learning programmes utilizing
      either VLE or ITV. Students rated courses using both technologies as moderately
      interactive. Significant differences between VLE and ITV were detected in student
      lecturer and student-student interactions, use of additional modes of
      communication, instructional design, technological interactivity and social
      rapport activities. The groups did not differ across a number of likely barriers
      to interaction and both also reported the need for more flexible and better paced
      instructional designs.

PMID- 16627312
TI  - Medical students' professionalism.

PMID- 16627313
TI  - How can experience in clinical and community settings contribute to early medical
      education? A BEME systematic review.
AB  - REVIEW DATE: Review period January 1992-December 2001. Final analysis July 2004
      January 2005. BACKGROUND AND REVIEW CONTEXT: There has been no rigorous
      systematic review of the outcomes of early exposure to clinical and community
      settings in medical education. OBJECTIVES OF REVIEW: Identify published empirical
      evidence of the effects of early experience in medical education, analyse it, and
      synthesize conclusions from it. Identify the strengths and limitations of the
      research effort to date, and identify objectives for future research. SEARCH
      STRATEGY: Ovid search of: BEI, ERIC, Medline, CINAHL and EMBASE Additional
      electronic searches of: Psychinfo, Timelit, EBM reviews, SIGLE, and the Cochrane
      databases. Hand-searches of:Medical Education, Medical Teacher, Academic
      Medicine, Teaching and Learning in Medicine, Advances in Health Sciences
      Education, Journal of Educational Psychology. CRITERIA:  DEFINITIONS: 
      EXPERIENCE: Authentic (real as opposed to simulated) human contact in a social or
      clinical context that enhances learning of health, illness and/or disease, and
      the role of the health professional. Early: What would traditionally have been
      regarded as the preclinical phase, usually the first 2 years. Inclusions: All
      empirical studies (verifiable, observational data) of early experience in the
      basic education of health professionals, whatever their design or methodology,
      including papers not in English. Evidence from other health care professions that
      could be applied to medicine was included. EXCLUSIONS: Not empirical; not early;
      post-basic; simulated rather than 'authentic' experience. DATA COLLECTION:
      Careful validation of selection processes. Coding by two reviewers onto an
      extensively modified version of the standard BEME coding sheet. Accumulation into
      an Access database. Secondary coding and synthesis of an interpretation. HEADLINE
      RESULTS: A total of 73 studies met the selection criteria and yielded 277
      educational outcomes; 116 of those outcomes (from 38 studies) were rated strong
      and important enough to include in a narrative synthesis of results; 76% of those
      outcomes were from descriptive studies and 24% from comparative studies. Early
      experience motivated and satisfied students of the health professions and helped
      them acclimatize to clinical environments, develop professionally, interact with
      patients with more confidence and less stress, develop self-reflection and
      appraisal skill, and develop a professional identity. It strengthened their
      learning and made it more real and relevant to clinical practice. It helped
      students learn about the structure and function of the healthcare system, and
      about preventive care and the role of health professionals. It supported the
      learning of both biomedical and behavioural/social sciences and helped students
      acquire communication and basic clinical skills. There were outcomes for
      beneficiaries other than students, including teachers, patients, populations,
      organizations and specialties. Early experience increased recruitment to primary
      care/rural medical practice, though mainly in US studies which introduced it for
      that specific purpose as part of a complex intervention. CONCLUSIONS: Early
      experience helps medical students socialize to their chosen profession. It helps
      them acquire a range of subject matter and makes their learning more real and
      relevant. It has potential benefits for other stakeholders, notably teachers and
      patients. It can influence career choices.

PMID- 16627314
TI  - Applying theory to practice in undergraduate education using high fidelity
      simulation.
AB  - High-fidelity patient simulation allows students to apply their theoretical
      knowledge of pharmacology and physiology to practice. The purpose of this study
      was to determine if experiential education using high-fidelity simulation
      improves undergraduate performance scores on simulation-based and written
      examinations. After receiving research ethics board approval, students completed
      a consent form and then answered a ten question multiple-choice quiz to identify
      their knowledge regarding the management of cardiac arrhythmias. Four simulation
      scenarios were presented and students worked through each scenario as a team.
      Faculty facilitated the sessions and feedback was given using students'
      videotaped performances as a template for discussion. Performance evaluation
      scores using predetermined checklists and global rating scales were completed.
      Students then reviewed the American Heart Association guidelines for the
      management of unstable cardiac arrhythmias. The afternoon session involved
      repetition of the four case scenarios with the same teams involved but different
      team leaders. Students then repeated the quiz they received in the morning.
      Descriptive statistics, paired t-test and repeated measures analysis of variance
      (ANOVA) were used to analyse results. Two hundred and ninety-nine students
      completed the study. There was a statistically significant improvement in
      performance on the pharmacology written test. Simulation team performance also
      statistically improved and a good correlation between checklist and global rating
      scores were demonstrated in all but one scenario. Student evaluation of the
      experience was extremely positive. High-fidelity simulation can be used to allow
      students to apply theoretical knowledge to practice in a safe and realistic
      environment. Results of this study indicate that simulation is a valuable
      learning experience and bridges the gap between theory and practice. Simulation
      technology has the potential to provide an enriching venue to examine the role of
      communication and dynamics of novice learners in team environments.

PMID- 16627315
TI  - Undergraduates' learning profile development: what is happening to the men?
AB  - Higher Education Institutions in the UK that offer programmes leading to
      professional registration with the Health Professions Council have been charged
      to provide the National Health Service with graduating autonomous professionals.
      Autonomous professionals are said to need: (a) self-directed learning skills and
      attributes; (b) a positive academic self-efficacy; (c) an internal academic locus
      of control and (d) a positive academic self-concept. The curricular influences on
      the development of these learning profile skills and attributes can be mapped
      overtime using batteries of self-rated inventories. In response to initiatives to
      widen access into Higher Education, increasing numbers of mature (aged 21 + years
      on admission) and male students are commencing undergraduate healthcare
      programmes. This study follows the learning profile changes of the mature, male
      physiotherapy students from two BSc (Hons) Physiotherapy cohorts and compares
      their development with that of their mature, female peers. Results suggest that
      the three-year undergraduate curriculum (validated 1997) had a negative effect on
      mature, male learning profile development. Most profile variables had fallen
      significantly overtime such that just prior to graduation the mature, male group
      was displaying a learning profile almost opposite to that suggested for an
      autonomous professional. The male group's cumulative assessment score was
      significantly lower than that for the mature, female group. The study explores
      the female dominance of the academic and clinical placement areas used to support
      undergraduate education, and considers the unintentional gender bias within
      elements of the curriculum and assessment design. Curricular adjustments made for
      the 2002 validated programme are discussed. With physiotherapy widening access
      initiatives striving to increase entry from non-traditional students (with mature
      and male students particularly targeted), this study suggests that the possible
      effects of curricular gender bias should not be overlooked.

PMID- 16627316
TI  - Twelve tips to promote excellence in medical teaching.
AB  - For medical teachers around the world, teaching duties have expanded beyond the
      classroom and include teaching small groups, assessment, providing instructional
      materials beyond the syllabus, problem-based learning, learner-centred teaching,
      clinical teaching on-the-fly--and the list goes on. Faculty development is
      essential to train medical faculty in essential educational theory and specific
      teaching skills as well as to encourage a flexible and learner-centred approach
      to teaching. Finally, self-reflection and critique of teaching techniques are
      vital to propel medical schools towards promoting and aiming for uncompromising
      excellence in medical education. The twelve tips described in this article
      relating to educating teachers, evaluating teaching and eradicating institutional
      apathy are simple measures that educational leaders can apply to promote
      excellence in teaching at their parent institutions. The tips introduce a multi
      dimensional approach to improving the overall quality of medical education
      consisting of measures aimed at individual teachers and those aimed at
      overhauling the teaching climate at medical institutions.

PMID- 16627317
TI  - Changes, trends and challenges of medical education in Latin America.
AB  - This paper briefly reviews the current situation of Latin American medical
      schools and the search to improve the quality and professionalism of medical
      education through the region. Institutional evaluation and accreditation programs
      based on nationally ongoing developing standards have been accepted, now
      optimized and complemented by the framework of the Global & International
      Standards of Medical Education working jointly with the WFME. More recently, the
      process has evolved to look into the quality of the outcomes of the medicals as
      seen by examinations implemented at the end of medical studies and the initiation
      of medical practice. In addition, there is vision for the application of new
      programs such as the global minimum essential requirements advanced by the
      Institute for International Medical Education (IIME). The PanAmerican Federation
      of Associations of Medical Schools (PAFAMS), an academic, non-governmental
      organization, is fostering the exchange of ideas and experiences among members,
      associations and affiliated medical schools geared to focus on the quality and
      professionalism of the graduates of medical schools in Latin America. These
      actions also aim to consolidate databases of information on medical education and
      innovative endeavors in continuing professional education and development through
      e-learning projects in the region.

PMID- 16627318
TI  - Discovering professionalism through guided reflection.
AB  - Doctors need to identify and understand the professional behaviours of both
      themselves and others. In order for students to think critically about these
      issues we encouraged them to use the tenets of the General Medical Council's
      Duties of a Doctor as a framework in which to reflect on the actions of
      healthcare professionals at work. Although the critical incident technique is a
      well-known process for encouraging reflection, little is known about its
      usefulness for assessment purposes in this setting. We aimed to discover the
      validity, feasibility and educational impact of the critical incident as an
      assessment method for first year students undertaking guided reflection in the
      context of their first exposure to multi-professional health and social care
      experiences. First year medical students submitted two critical incidents they
      had observed during multi-professional health and social care attachments and an
      evaluation of their experiences. Students engaged in the reflective cycle on the
      professional behaviours of others providing evidence of a varied range of
      situations. With adequate preparation, junior students are able to reflect on
      social and healthcare experiences using the Duties of a Doctor as a framework.
      Critical incidents are a valid and feasible method for assessing students'
      reflections on professionalism, with good educational impact.

PMID- 16627319
TI  - Teaching the art of doctoring: an innovative medical student elective.
AB  - The authors describe a longitudinal third- and fourth-year elective, 'The Art of
      Doctoring', introduced in an attempt to counteract perceived frustration and
      cynicism in medical students at their home institution during the clinical years.
      The course goals aimed at helping students to develop self-reflective skills;
      improve awareness of and ability to modify personal attitudes and behaviors that
      compromise patient care; increase altruism, empathy and compassion toward
      patients; and sustain commitment to patient care, service and personal well
      being. These goals were accomplished through introduction and development of five
      skill sets: learning from role models and peers; on-site readings of works by
      medical student- and physician-authors; self- and other-observation; self
      reflective techniques; and case-based problem-solving. The course involved
      regular in-class exercises and homework assignments, as well as a personal
      project related to improving personal compassion, caring and empathy toward
      patients. Students also learned to use a coping algorithm to approach problematic
      clinical and interpersonal situations. Class discussions revealed three issues of
      recurring importance to students: loss of idealism, non-compliant patients, and
      indifferent, harsh or otherwise unpleasant attendings and residents. Quantitative
      and qualitative student evaluations overall indicated a generally favorable
      response to the course. Problems and barriers included attendance difficulties
      and variable levels of student engagement. Future directions for this type of
      educational intervention are considered, as well as its implications for medical
      education.

PMID- 16627320
TI  - Reflective practice in physiotherapy curricula: a survey of UK university based
      professional practice coordinators.
AB  - There has been recent increasing interest in reflective practice within
      physiotherapy education as a method for reducing the 'theory-practice gap' and as
      a means of articulating, exposing and developing knowledge embedded in practice.
      Several contrasting theories have been developed to explain the role, place,
      purpose and definition of reflection in learning and teaching; however, much of
      the research to date has relied on theoretical debate rather than high quality
      empirical evidence. The aim of this paper was therefore, to report how a group of
      United Kingdom (UK) based physiotherapy Professional Practice Coordinators (n =
      33) with their unique insight into the concept from both the academic and
      clinical perspective viewed and interpreted the use of reflective practice within
      their physiotherapy curriculum. Consent for the study was obtained via the
      professional body (The Chartered Society of Physiotherapists) (CSP) and data was
      collected via postal questionnaire. Results indicated a diversity of experience
      in respondents both in terms of their role as Coordinator and their training in
      reflective practice. There was also no clear consensus regarding facilitative
      models or assessment methods even though the majority of coordinators believed
      that reflective practice should be considered to be a central component of
      physiotherapy teaching strategies. The results of this survey provide a focus for
      further empirical research into reflective practice as part of the physiotherapy
      curricula, while advancing the understanding of reflective practice from a
      broader perspective and clarifying the benefits to students, teachers, patients
      and practitioners.

PMID- 16627321
TI  - Developing and evaluating professionalism.
AB  - Professional behaviour, being one of the domains of professionalism, is an area
      of medical education that has long been of concern to medical educators. At
      Hacettepe University, our main goal is to have students become conscious of
      professional identity, values, responsibilities and the physician-patient
      relationship. We welcome our new students with an opening ceremony on their first
      day and two months later, the students start the course called "Health-Illness
      Concepts and Medical Professional Identity". Students are expected to discuss the
      subjects given to them as scenarios or arguments. The aim of our study is to
      determine whether the course leads to a positive change in students' attitudes,
      indicating the attainment of those attributes that reflect professionalism. On
      the first and the last days of the course, a questionnaire was delivered to the
      students. Any positive change in preferences between the two questionnaires is
      identified as an achievement of that attribute. As a result we found that in all
      of the seven attributes there were positive changes in the students' attitudes.
      Positive changes varied from 48% to 84% and all were statistically significant.
      Using more interactive techniques helped the students to make larger percentage
      changes in their awareness of these professional attributes.

PMID- 16627322
TI  - Information and communication technologies in higher education: evidence-based
      practices in medical education.
AB  - In contrast to traditional meta-analyses of research, an alternative overview and
      analysis of the research literature on the impact of information and
      communication technologies (ICT) in medical education is presented in this
      article. A distinction is made between studies that have been set up at the micro
      level of the teaching and learning situation and studies on meso-level issues. At
      the micro-level, ICT is hypothesized to foster three basic information processing
      activities: presentation, organization, and integration of information. Next to
      this, ICT is expected to foster collaborative learning in the medical knowledge
      domain. Empirical evidence supports the potential of ICT to introduce students to
      advanced graphical representations but the studies also stress the importance of
      prior knowledge and the need for real-life tactile and practical experiences. The
      number of empirical studies focusing on the impact of ICT on information
      organization is restricted but the results suggest a positive impact on student
      attitudes and relevant learning gains. However, again, students need a relevant
      level of prior knowledge. Empirical studies focusing on the impact of ICT on
      information integration highlight the positive impact of ICT-based assessment and
      computer simulations; for the latter this is especially the case when novices are
      involved, and when they master the prerequisite ICT skills. Little empirical
      evidence is available regarding the impact of computer games. Research results
      support the positive impact of ICT-based collaboration but care has to be taken
      when skills development is pursued. At the meso-level, the available empirical
      evidence highlights the positive impact of ICT to promote the efficiency of
      learning arrangements. Research grounds the key position of ICT in a state-of-the
      art medical curriculum. Recent developments focusing on repositories of learning
      materials for medical education have yet not been evaluated. The article
      concludes by stressing the need for evaluative studies, especially in the
      promising field of ICT-based collaborative learning. Furthermore, the importance
      to be attached to the position and qualifications of the teaching staff is
      emphasized.

PMID- 16627323
TI  - Disorganized junior doctors fail the MRCP (UK).
AB  - Career progression during undergraduate and early postgraduate years is currently
      determined by successfully passing examinations. Both academic factors (secondary
      school examination results, learning style and training opportunities) and non
      academic factors (maturity, ethnic origin, gender and motivation) have been
      identified as predicting examination outcome. Few studies have examined
      organization skills. Disorganized medical students are more likely to perform
      poorly in end-of-year examinations but this observation has not been examined in
      junior doctors. This study asked whether organization skills relate to
      examination outcome amongst junior doctors taking the clinical Part II
      examination for the Membership of the Royal College of Physicians (Practical
      Assessment of Clinical Examination Skills). The study was conducted prospectively
      at four consecutive clinical courses that provided clinical teaching and practice
      to prepare trainees for the examination. Arrival time at registration for the
      course was the chosen surrogate for organization skills. Trainees were advised
      that they should arrive promptly at 8.00 a.m. for registration and it was
      explained that the course would start at 8.30 a.m. Recorded arrival times were
      compared with the pass lists published by the Royal College of Physicians. The
      mean arrival time was 8.17 a.m. A total of 81 doctors (53.3%) passed the
      examination with a mean arrival time of 8.14 a.m. However, 71 doctors failed the
      exam and arrived, on average, six minutes later than doctors who passed
      (p?=?0.006). Better-prepared junior doctors were more likely to pass the final
      examination. Arriving on time represents a composite of several skills involved
      in the planning of appropriate travel arrangements and is therefore a valid
      marker of organization skills and preparation. This novel study has shown that
      good time-keeping skills are positively associated with examination outcome.

PMID- 16627324
TI  - A questionnaire survey of students' perceptions of nurse tutor teaching in a
      clinical skills learning programme.
AB  - Changes in medical education and in the environments in which students learn have
      brought about new ways of learning in undergraduate medical curricula. Amongst
      these have been the establishment of courses in clinical skills learning to
      address concerns of deficient skills amongst newly qualified doctors. Curriculum
      reform at Liverpool, UK, included extensive and early learning of clinical
      skills. Nurse tutors provide full-time teaching support in a single Clinical
      Skills Resource Centre. They work alongside medically qualified tutors in
      delivering a clinical skills learning programme. This study aimed to explore
      students' opinion of nurses teaching clinical skills and to compare that to their
      opinion of teaching by medically qualified clinicians. A questionnaire survey was
      used to gain the views of 206 first-year medical students. Overall, students were
      strongly supportive in their opinion of nurse tutors. Some small statistically
      significant differences are probably of little or no educational significance.
      This role for nurses stresses the importance of interprofessional teachers in
      undergraduate healthcare education.

PMID- 16627325
TI  - Breaking bad news: qualitative evaluation of an interprofessional learning
      opportunity.
AB  - This paper analyses the effects of bringing together a small group of nursing and
      medical students to learn the skills needed to break bad news to patients. It
      outlines the qualitative and quantitative methods used, to provide the reader
      with a comprehensive account of the teaching, learning and research strategies
      drawn on during the study. The paper examines the evaluation phase, as this
      aspect is of greatest import if such initiatives are to flourish. The facet of
      the study analysed in detail concerns the students' responses to the open-ended
      qualitative questionnaires. In coding the data, three researchers independently
      highlighted a series of themes associated with the benefits and hazards of
      nursing and medical students learning and working together. Finally, the paper
      closes by arguing that trust and mutual respect are vital ingredients if
      collaborative working is to become part of the medical and nursing curriculum.

PMID- 16627326
TI  - Not just another multi-professional course! Part 1. Rationale for a
      transformative curriculum.
AB  - Undergraduate inter- and multi-professional education has traditionally aimed to
      develop health professionals who are able to collaborate effectively in
      comprehensive healthcare delivery. The respective professions learn from and
      about each other through comparisons of roles, responsibilities, powers, duties
      and perspectives in order to promote integrated service. Described here is the
      educational rationale of a multi-professional course with a difference; one that
      injects value to undergraduate health professional education through the
      development of critical cross-field knowledge, skills and attitudes that unite
      rather than differentiate professions. The aim of this course, offered at the
      Faculty of Health Sciences, University of Cape Town, is to lay an integrated, pan
      professional foundation for the advancement of collective commitment to and
      understanding of national health and social development objectives such as
      primary health care, human rights and professionalism. Pan-professional refers to
      curriculum content that is core and of critical relevance to all participating
      professions. What is learned, how it is learned, how learning is facilitated and
      how it is applied, has been co-constructed by a multi-professional design team
      representing a range of health professions (audiology, medicine, occupational
      therapy, nursing, physiotherapy and speech therapy) and academic disciplines
      (anthropology, sociology, psychology, history, African studies and social
      development, information technology and language literacy). Education specialists
      facilitate the ongoing design process ensuring that the structure and content of
      the curriculum complies with contemporary adult learning principles and national
      higher education imperatives. Designing the original curriculum required the
      deconstruction of intra-professional and disciplinary canons of knowledge and
      ways of 'doing things' in order to identify and develop shared interpretations of
      critical epistemology and axiology for health professional practice in the South
      African context. This enabled the alignment of the learning objectives, at first
      year level, of all the represented professions. The educational rationale guiding
      the curriculum design process is discussed in Part 1 of two articles. Part 2
      describes the 'nuts and bolts' or practicalities of the curriculum design
      process.

PMID- 16627327
TI  - Clinical role models are important in the early years of a problem-based learning
      curriculum.
AB  - Following a comprehensive study of the role models identified by the first five
      years of students in a traditional medical programme, it was hypothesized that
      with curriculum reform clinical role models would assume greater importance
      earlier in the undergraduate medical programme. Indeed, when compared with their
      first- and second-year traditional curriculum colleagues, more problem-based
      learning students identified role models. Almost four times as many identified
      faculty role models (largely medically qualified) in comparison with their
      traditional curriculum counterparts. Concomitant with this increase was a decline
      in the selection by the PBL students of family members, friends and other
      students as role models. For all cohorts, however, the mother was the most
      important role model. Since students in integrated curricula have earlier
      clinical experience and patient contact, they interact with clinicians in
      hospitals and clinics as well as in the academic environment of the small-group
      tutorial and lecture theatres. Academic faculty members, particularly clinicians,
      need to be aware that students take note of their attitudes and behaviour as
      members of the medical profession, a profession that students had chosen as a
      career. Retraining of senior doctors from the traditional curriculum might be
      necessary to ensure that all clinicians have an equivalent understanding of
      patient care.

PMID- 16627328
TI  - Person-task-context: a model for designing curriculum and in-training assessment
      in postgraduate education.
AB  - Structured curricula for senior house officers have often been lacking. The aim
      of this study was to trial a person-task-context model in designing a curriculum
      and in-training assessment (ITA) programme for SHOs in internal medicine. A
      working group designed the programme based on triangulation of information from
      interviews with trainees and programme directors, analysis of patient case mix
      and national quality assurance data. The interview data showed that the main
      difference currently between trainee levels was in expected degree of
      responsibility for patient management rather than in actual tasks. Key learning
      needs were how to take a structured approach to the tasks and get an overview of
      situations. SHOs expressed a need for explicit learning goals and standards of
      performance. SHOs requested formal teaching in non-medical aspects of competence
      such as communication, interpersonal skills and professionalism. This article
      points out how consideration of the type of trainees involved, the tasks they
      must do and learn, and the context in which they work are important in designing
      postgraduate curricula. The person-task-context model can be used to tailor
      curricula and ITA that support learning and may be especially beneficial in
      promoting learning in non-dominant areas of a specialty.

PMID- 16627329
TI  - Learning by doing: developing fellows' academic skills through collaborative
      research.
AB  - Physicians in postgraduate training are expected to learn research methods but
      how best to achieve that curricular goal is unclear. This article describes a
      novel educational approach to develop research skills among infectious disease
      fellows. Five infectious disease fellows and two faculty members participated in
      a collaborative research project as a vehicle for active, problem-based learning.
      During the learning experience several tasks with specific learning objectives
      were achieved. The authors evaluated the weaknesses and strengths of the
      collaborative research project as an educational program. This problem-based
      approach for learning research methods seems more effective than traditional
      methods and may be applicable to a broad range of training programs.

PMID- 16627330
TI  - You couldn't make it up. Or could you?
AB  - Revalidation is the new method by which doctors in the UK will stay on the
      medical register. Most doctors will take the appraisal route to revalidation-
      that is, they will undergo annual appraisals and five successful appraisals will
      result in revalidation. So there is a lot riding on appraisal. But it relies
      almost completely on trust. And in a situation that is based on absolute trust
      there are endless opportunities for that trust to be broken. Doctors will be
      encouraged to look at how they are doing as a doctor in terms of the General
      Medical Council's characteristics of a good doctor-such as providing good
      clinical care and maintaining good relationships with patients. But doctors can
      fabricate evidence to show that they work to these standards. There is anecdotal
      evidence that this happens and also published evidence that medical students
      cheat and that such cheating may predict dishonesty later on. One study from
      outside medicine showed that some learners doing a postgraduate diploma in
      education admitted to cheating. The current system of appraisal and revalidation
      is currently under review in light of the Shipman inquiry and many doctors are
      scared that appraisal may be a stepping stone towards assessment. A guaranteed
      way of speeding up the drive towards introducing assessment is not taking
      appraisal seriously.

PMID- 16627331
TI  - What influences medical school choice?
AB  - In this six year study, we asked new students at the University of Liverpool, why
      they had chosen it. We asked students to tell us what they had considered when
      they made their decision about Liverpool in a questionnaire at first
      registration. Ninety-six percent of students in 2001-2002, compared with 66% in
      1996-1997, cited the course as most important when choosing a medical school. The
      type of course offered by medical schools has become important for applicants.
      The importance of the course for potential students is increasing, but applicants
      will still consider the whole package: course, students and city when choosing a
      medical school.

PMID- 16627332
TI  - Addressing the needs and priorities of medical teachers through a collaborative
      intensive faculty development programme.
AB  - Faculty development in medical education is crucial for developing and sustaining
      quality education in medical schools. However, examples of successful intensive
      programmes based on experiential and collaborative learning are generally lacking
      in the literature. The Medical Education Unit of National University of Singapore
      conducted a three-day intensive programme on core competences in medical
      education. This paper highlights the process of programme development, programme
      structure, challenges faced and strategies adopted. It also describes the
      approach taken to educational programme evaluation along with the results. The
      programme structure was based on experiential and collaborative learning models.
      Participants contributed to all activities and emerged as facilitators and
      learners to gain first-hand experience of the complex educational processes. Each
      individual session was sequential with a brief plenary, demonstration, practicum
      and reflection. Pre-programme needs assessment showed that even the experienced
      teachers perceived a need to further improve their educational competencies.

PMID- 16627334
TI  - Progress testing.

PMID- 16627335
TI  - Do you know?

PMID- 16627339
TI  - Can we use monoclonal antibodies to help T cells fight tumors?

PMID- 16627340
TI  - CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce
      T-cell responses against AML cells in an autologous culture system.
AB  - BACKGROUND: Cells from AML patients can differentiate into the phenotype of DC
      when cultured with GM-CSF and IL-4. Such cytokine-treated AML-derived DC (AML-DC)
      can stimulate autologous T cells. In this study we examined whether an anti-CTLA
      4 MAb (MDX-010) could enhance the generation of autologous anti-AML T cells.
      METHODS: MAb MDX-010 was added to AML PBMC cultures in the presence of GM-CSF and
      IL-4, a previously reported AML-DC culture method of generating anti-AML T cells.
      T-cell activation and proliferation were examined thereafter. RESULTS: Addition
      of MDX-010 to GM-CSF/IL-4-conditioned AML-DC cultures induced a mean seven-fold
      increase in the numbers of autologous T cells compared with cultures without MDX
      010 (P < 0.007). T cells stimulated by AML-DC with CTLA-4 blockade were
      significantly more cytotoxic towards autologous AML cells than those without MDX
      010 (42 +/- 23% vs. 26 +/- 15%, E:T ratio of 20). T cells stimulated by AML-DC
      with CTLA-4 blockade had significantly greater proportions of T cells producing
      IFN-gamma in response to autologous AML cells than those cultured with AML-DC
      alone (10.7 +/- 4.7% vs. 4.5 +/- 2.4% for CD4+ IFN-gamma+ CD69+ and 9.8 +/- 4.1%
      vs. 4 +/- 2.1% for CD8+ IFN-gamma+ CD69+ with or without MDX-010; n = 7; P <
      0.007, P < 0.003, respectively). DISCUSSION: CTLA-4 blockade enhances the
      activity and numbers of AML-reactive T cells that can be stimulated by autologous
      AML-DC and may enhance the efficacy of adoptive immunotherapy of AML.

PMID- 16627341
TI  - The apoptotic and proliferative fate of cytokine-induced killer cells after
      redirection to tumor cells with bispecific Ab.
AB  - BACKGROUND: Cytokine-induced killer (CIK) cells are ex vivo expanded T cells with
      co-expression of CD3 and CD56 and NK activity. They have recently been evaluated
      in a phase I/II clinical trial against malignant lymphoma. Bispecific Ab (bsAb)
      redirect CIK cells to tumor targets, thus enhancing their cytotoxicity. While
      bsAb may improve T-cell mediated anti-tumor activity, little is known about the
      fate of effector cells upon redirection to tumor targets using a bsAb. METHODS:
      Using ex vivo-activated CIK cells, Her2/neu expressing breast and ovarian cell
      lines and a F(ab')2 Her2/neu x CD3 bsAb, we investigated the anti-tumor activity
      and the proliferative and apoptotic outcome of CIK cells. RESULTS: When
      redirected to tumor targets with bsAb, there was a significant increase in anti
      tumor activity as well as an increase in both CIK cell proliferation and
      apoptosis. The addition of agonistic Ab against CD28 did not significantly
      increase proliferation or apoptosis of CIK cells redirected to CD80- and CD86-
      tumor targets. To attempt to reduce T-cell apoptosis, we incubated CIK cells in
      the presence of the pan-caspase inhibitor z-VAD-fmk, which led to a partial
      reduction in T-cell apoptosis without increasing cellular cytotoxicity.
      DISCUSSION: bsAb are effective in redirecting activated T cells to tumor targets
      and such redirection leads to both T-cell proliferation and apoptosis that are
      not altered by co-stimulation through CD28. Effector cell apoptosis can be
      reduced by using a caspase inhibitor but this does not increase CIK cell
      cytotoxicity.

PMID- 16627342
TI  - Expression of aberrantly glycosylated tumor mucin-1 on human DC after
      transduction with a fiber-modified adenoviral vector.
AB  - BACKGROUND: DC-presenting tumor Ag are currently being developed to be used as a
      vaccine in human cancer immunotherapy. To increase chances for successful therapy
      it is important to deliver full-length tumor Ag instead of loading single
      peptides. METHODS: In this study we used a fiber-modified adenoviral vector
      (rAd5F35) containing full-length tumor Ag cDNA to transduce human monocyte (Mo)
      derived DC in vitro. Cells were efficiently transduced and survived for at least
      3 days after adenoviral transduction. Phenotype and function after maturation of
      Mo-DC were not impaired by infection with adenovirus particles. Expression of the
      tumor-associated Ag mucin-1 (MUC1) was detected using MAb defining different MUC1
      glycoforms. RESULTS: Non-transduced mature Mo-DC express endogenous MUC1 with
      normal glycosylation. After transduction with the rAd5F35-MUC1 adenoviral vector,
      Mo-DC also expressed MUC1 with tumor-associated glycosylation (Tn and T
      glycoforms), although no changes in mRNA levels of relevant glycosyltransferases
      could be demonstrated. DISCUSSION: The presence of aberrantly glycosylated MUC1
      may influence Ag presentation of the tumor glycoforms of MUC1 to immune cells,
      affecting tumor cell killing. These findings could be highly relevant to
      developing strategies for cancer immunotherapy based on DC vaccines using MUC1 as
      tumor Ag.

PMID- 16627343
TI  - Transduction with a fiber-modified adenoviral vector is superior to non-viral
      nucleofection for expressing tumor-associated Ag mucin-1 in human DC.
AB  - BACKGROUND: DC-presenting tumor Ag are currently being developed to be used as a
      vaccine in human cancer immunotherapy. To increase the chances for successful
      therapy it is important to deliver full-length tumor Ag instead of loading single
      peptides. Methodologically, several recombinant DNA delivery techniques have been
      used. METHODS: In this study we compared nucleofection, an optimized form of
      electroporation, and adenoviral transduction regarding their efficiency to
      transduce human monocyte-derived (Mo-) DC in vitro. Expression of the tumor
      associated Ag mucin-1 (MUC1) after adenoviral transduction (rAd5Fib35-MUC1) was
      determined using two MAb. RESULTS: We showed that the viability of cells and
      percentage of green fluorescent protein (GFP)-positive cells after transduction
      with a fiber-modified adenoviral vector (rAd5F35-GFP) was much higher than after
      nucleofection. Furthermore, phenotype and function of DC were not impaired by
      infection with adenovirus particles. Cells matured normally; up-regulation of
      CD40, CD80, CD83, CD86 and HLA-DR was not affected by adenoviral transduction.
      The capacity to stimulate naive T-cell proliferation was preserved and no change
      in IL-10 production was observed. Production of IL-12 increased up to 500-fold
      upon adenoviral transduction, considered to contribute positively to an anti
      tumor immune response. Non-transduced mature DC expressed low levels of
      endogenous MUC1. After transduction with the rAd5F35-MUC1 adenoviral vector, a
      100-fold increase in MUC1 expression by DC was observed. DISCUSSION: The use of
      the fiber-modified adenoviral vector presented here may therefore be favorable
      compared with non-viral gene delivery systems for DC that will be used in cancer
      immunotherapy.

PMID- 16627344
TI  - General safety guidances in stem cell bank installations.
AB  - The use of cell cultures in research and in regenerative medicine programs has
      increased in the past few years, and control of the risks inherent to these
      procedures should be increased. People who work in stem cell bank installations
      should be aware of the risks implied in their work and take necessary self
      protection measures for the known and unidentified risks. Work in stem cell bank
      installations is subject to different types of risks, such as toxicologic,
      carcinogen and, mainly, infectious risks. Different types of safety measurements
      should be distinguished and secured, for example for protection of personnel,
      protection of the cell cultures and protection in general of humans and the
      environment.

PMID- 16627345
TI  - Novel cryoprotectant significantly improves the post-thaw recovery and quality of
      HSC from CB.
AB  - BACKGROUND: Hematopoietic stem cells (HSC) have traditionally been frozen using
      the cryoprotectant DMSO in dextran-40, saline or albumin. However, the process of
      freezing and thawing results in loss of HSC numbers and/or function. METHODS:
      This study investigated the use of CryoStor for the freezing of HSC from cord
      blood (CB). CB donations (n = 30) were collected under an Institutional Ethics
      Committee-approved protocol, volume reduced and frozen using three different
      methods of cryoprotection. Aliquots were frozen with either 10% DMSO in dextran
      40, 10% DMSO in CryoStor or 5% DMSO in CryoStor. Prior to freezing samples were
      separated for nucleated cell (NC) and CD34+ counts and assessment of CD34+
      viability. Aliquots were frozen and kept in vapor phase nitrogen for a minimum of
      72 h. Vials were rapidly thawed at 37 degrees C and tested for NC and CD34+
      counts and CD34+ viability and colony-forming unit (CFU) assay. RESULTS: Cells
      frozen with CryoStor in 10% DMSO had significantly improved NC (P < 0.001), CD34+
      recovery, viable CD34+ (P < 0.001) and CFU numbers (P < 0.001) compared with
      dextran in 10% DMSO. CryoStor in 5% DMSO resulted in significantly improved NC (P
      < 0.001) and CFU (P < 0.001). DISCUSSION: These results suggest that improved HSC
      recovery, viability and functionality can be obtained using CryoStor with 10%
      DMSO and that similar if not better numbers can be obtained with 5% DMSO compared
      with dextran-40 with 10% DMSO.

PMID- 16627346
TI  - Introduction of a validation concept for a PCR-based Mycoplasma detection assay.
AB  - BACKGROUND: Mycoplasma contamination is amongst the most frequently occurring
      problems associated with cell cultures. In order to meet the legal requirements
      (European Pharmacopoeia and FDA) for Mycoplasma testing of cell lines and
      therapeutics, we have developed a PCR-based method to detect mycoplasms and
      introduce a validation concept. METHODS: The PCR assay specifically amplifies a
      280-bp DNA fragment of the gene coding for the 16S rDNA. Simultaneous
      amplification of an artificial oligonucleotide containing primer-binding sites
      allowed control of the efficacy of the PCR. The validation of the PCR assay was
      performed with two Mycoplasma reference strains, M. orale and M. pneumoniae. The
      validation concept included (i) cultivation of M. orale and M. pneumoniae in
      medium with an indicator for bacterial metabolism, (ii) determination of the
      color-changing units (CCU) in repeated dilution experiments and (iii) correlation
      of the PCR results with CCU values. RESULTS: The detection range was found to
      include all Mycoplasma species most commonly found in cell cultures. The
      analytical sensitivity of the PCR was the CCU equivalent of 100 for M. orale and
      M. pneumoniae. Probit analysis revealed a detection probability of 9% for a mean
      concentration of 1222 (935-1844) CCU/mL for M. pneumoniae and 2547 (1584-10,352)
      CCU/mL for M. orale. DISCUSSION: The validation of the Mycoplasma detection assay
      supported PCR as an attractive diagnostic tool that will help manage the
      important issue of Mycoplasma contamination of cell cultures.

PMID- 16627347
TI  - SCF modulates organ distribution and hematopoietic engraftment of CB-derived
      pluripotent HPC transplanted in NOD/SCID mice.
AB  - BACKGROUND: During the engraftment process of transplanted HPC, the beta 1
      integrins play an important role. An increased expression and adhesive function
      of these integrins has been shown in hematopoietic cell lines and peripheral
      blood-derived HPC after stimulation with SCF. In this study, we investigated the
      influence of SCF on the engraftment capability and tissue distribution of cord
      blood (CB) cells transplanted into NOD/SCID mice. METHODS: CB-derived mononuclear
      cells were injected i.v. into 40 sublethally irradiated NOD/SCID mice with or
      without the addition of 10 microg SCF/ mouse. Six weeks later, BM, liver,
      kidneys, brain and testicular tissue were analyzed for the prevalence of human
      cells. RESULTS: The mean proportion of human CD45+ CD71+ cells within the BM of
      all engrafted mice receiving SCF in addition to the cells was 1.7-fold higher
      than in the respective controls. By immunohistochemical staining, human cells
      were found in liver and kidneys of the engrafted animals, but not in neural
      tissues or testicles. In the kidneys, the proportion of human cells rose
      significantly from 0.07 +/- 0.3% to 0.24 +/- 0.05% with treatment with SCF,
      compared with untreated controls. Single human cells in the liver additionally
      stained positive for human albumin, indicating organ-specific differentiation of
      the transplanted cells. DISCUSSION: Our results indicate that stimulation with
      SCF modulates the tissue distribution of the progeny of the transplanted cells
      and improves the hematopoietic engraftment potential of transplanted CB cells.

PMID- 16627348
TI  - The role of response selection in sequence learning.
AB  - We investigated the role of response selection in sequence learning in the serial
      reaction time (SRT) task, by manipulating stimulus-response compatibility. Under
      conditions in which other types of learning, like perceptual, response-based, and
      response-effect learning, were unaffected, sequence learning was better with an
      incompatible than with a compatible stimulus-response mapping. Stimulus
      discriminability, on the other hand, had no influence on the amount of sequence
      learning. This indicates that the compatibility effects cannot be accounted for
      by a different level of task difficulty. Relating our results to the dimensional
      overlap model (Kornblum, Hasbroucq, & Osman, 1990), which assumes that
      incompatible stimulus-response mappings require more controlled response
      selection than do compatible stimulus-response mapping, we suggest that sequence
      learning in the SRT task is particularly effective when response selection occurs
      in a controlled way.

PMID- 16627349
TI  - Inattentional blindness for negative relationships in human causal learning.
AB  - The present study focuses on the effect of selective attention on causal
      learning. Three effects of the level of attention to predictive symptoms in
      positive and negative contingency learning tasks are reported. First,
      participants accurately detected a positive relationship between an incidental
      cue and a contingent outcome, although judgements were slightly lower than those
      for the attended cue. Second, participants were unable to detect negative
      relationships between incidental cues and outcomes, which suggests a major role
      of selective attention in this type of learning. Third, participants retrieved
      the frequency of each trial type more accurately in the attended conditions than
      in the incidental conditions. These findings show how attention guides and
      constrains human causal learning and reveal an inattentional blindness effect for
      negative contingency learning.

PMID- 16627350
TI  - The Espinet and the perceptual learning effects in flavour aversion conditioning:
      do they depend on a common inhibitory mechanism?
AB  - In three experiments rats were given short or long preexposure (4 or 10 sessions)
      to two compound flavours, AX and BX, according to an intermixed or a blocked
      schedule. Following preexposure, aversion conditioning trials were given with AX
      as the conditioned stimulus (CS). In Experiments 1 and 2, retardation and
      summation tests were then carried out to assess the inhibitory properties of B
      (an Espinet procedure). In Experiment 3, test trials evaluated generalization
      from AX to BX (the standard perceptual learning procedure). The results showed
      that B performed as an inhibitor of the unconditioned stimulus (US; an Espinet
      effect) only after long intermixed preexposure, whereas a reliable perceptual
      learning effect was observed both after short and after long preexposure. The
      observation that B had no detectable inhibitory properties after short
      preexposure casts doubt on the suggestion that inhibitory learning is responsible
      for perceptual learning after brief exposure to AX and BX.

PMID- 16627351
TI  - Successful differential evaluative conditioning using simultaneous and trace
      conditioning procedures in the picture-picture paradigm.
AB  - This paper describes a study designed to investigate the efficacy of two
      traditional classical conditioning procedures in generating evaluative
      conditioning (EC) in the picture-picture paradigm in human participants.
      Differential EC was found using both simultaneous and trace conditioning
      procedures. In addition, the use of a block-subblock (BSB) nonpaired control
      condition and full counterbalancing of conditioned stimulus-unconditioned
      stimulus (CS-UCS) pairings across participants indicated that the observed EC
      effects were the result of associative learning. Examination of whether
      successful conditioning could take place with or without conscious awareness of
      CS-UCS contingencies was inconclusive. The results provide evidence for EC as an
      associative process and also provide some insight into the possible conditioning
      parameters that might successfully generate EC.

PMID- 16627352
TI  - Memory for object location and route direction in virtual large-scale space.
AB  - In everyday life people have to deal with tasks such as finding a novel path to a
      certain goal location, finding one's way back, finding a short cut, or making a
      detour. In all of these tasks people acquire route knowledge. For finding the
      same way back they have to remember locations of objects like buildings and
      additionally direction changes. In three experiments using recognition tasks as
      well as conscious and unconscious spatial priming paradigms memory processes
      underlying wayfinding behaviour were investigated. Participants learned a route
      through a virtual environment with objects either placed at intersections (i.e.,
      decision points) where another route could be chosen or placed along the route
      (non-decision points). Analyses indicate first that objects placed at decision
      points are recognized faster than other objects. Second, they indicate that the
      direction in which a route is travelled is represented only at locations that are
      relevant for wayfinding (e.g., decision points). The results point out the
      efficient way in which memory for object location and memory for route direction
      interact.

PMID- 16627353
TI  - Action-feature integration blinds to feature-overlapping perceptual events:
      evidence from manual and vocal actions.
AB  - Previous studies showed that the identification of a left- or right-pointing
      arrowhead is impaired when it appears while planning and executing a spatially
      compatible left or right keypress (Musseler & Hommel, 1997a). We attribute this
      effect to stimulus processing and action control operating on the same feature
      codes so that, once a code is integrated in an action plan, it is less available
      for perceptual processing. In three pairs of experiments we tested the generality
      of this account by using stimulus-response combinations other than arrows and
      manual keypresses. Planning manual left-right keypressing actions impaired the
      identification of spatially corresponding arrows but not of words with congruent
      meaning. On the contrary, planning to say "left" or "right" impaired the
      identification of corresponding spatial words but not of congruent arrows. Thus,
      as the feature-integration approach suggests, stimulus identification is impaired
      only with overlap of perceptual or perceptually derived stimulus and response
      features while mere semantic congruence is insufficient.

PMID- 16627354
TI  - Programming strategies for rapid aiming movements under simple and choice
      reaction time conditions.
AB  - Increases in reaction time (RT) as a function of response complexity have been
      shown to differ between simple and choice RT tasks. Of interest in the present
      study was whether the influence of response complexity on RT depends on the
      extent to which movements are programmed in advance of movement initiation versus
      during execution (i.e., online). The task consisted of manual aiming movements to
      one or two targets (one- vs. two-element responses) under simple and choice RT
      conditions. The probe RT technique was employed to assess attention demands
      during RT and movement execution. Simple RT was greater for the two- than for the
      single-target responses but choice RT was not influenced by the number of
      elements. In both RT tasks, reaction times to the probe increased as a function
      of number of elements when the probe occurred during movement execution. The
      presence of the probe also caused an increase in aiming errors in the simple but
      not choice RT task. These findings indicated that online programming was
      occurring in both RT tasks. In the simple RT task, increased executive control
      mediated the integration between response elements through the utilization of
      visual feedback to facilitate the implementation of the second element.

PMID- 16627355
TI  - Effects of unit formation on the perception of a changing sound.
AB  - The effects of subunit formation on adult listeners' ability to notice changes in
      a continuous spectral gradient of sound were studied. Results of this experiment
      support the idea that the auditory system processes information differently
      within a unit, and that this processing does not occur unless the perceptual
      system detects unit boundaries. In this experiment, silences were inserted into a
      continuously changing sound to cause the formation of short units. Listeners
      noticed the change earlier in conditions with silences inserted than in to
      conditions where the transition was either unbroken or broken by loud noise
      bursts. Results are discussed in terms of two processes, one that accentuates
      stimulus properties present at moments of onset and offset, and a second that
      uses onsets and offsets to signal the beginnings and ends of units and reduces
      the change perceived within units.

PMID- 16627356
TI  - Decomposing retrieval and integration in memory for actions: a multinomial
      modeling approach.
AB  - Typically, action phrases are recalled better if participants are asked to enact
      the phrases than if they are just asked to remember them. When investigating
      which processes constitute this enactment effect a difficulty is that observable
      effects in standard memory tests are ambiguous because such tests require several
      processes. In the present article, we introduce a multinomial model that
      decomposes observable memory performance into a retrieval parameter and a
      parameter concerning the item-specific processing and integration of an action
      phrase. These parameters are estimated from free recall and cued recall
      performance. The model fitted the data of two experiments designed to test it.
      Experiment 1 demonstrated the basic usefulness of the model by showing expected
      differences in the integration parameter in the absence of unexpected differences
      in the retrieval parameter. Experiment 2 extended the conditions under which the
      model is useful by showing expected differences in the retrieval parameter even
      in the presence of unexpected differences in the integration parameter. Together,
      these findings support our theoretical framework according to which enactment
      generally boosts integration of action phrases, but increases retrieval only for
      phrases with context cues.

PMID- 16627357
TI  - The influence of phoneme position overlap on the phonemic similarity effect in
      nonword recall.
AB  - The current research examined the predictions that short-term memory models
      generate for the phonological similarity effect, when similarity was defined in
      different ways. Three serial recall experiments with consonant-vowel-consonant
      (CVC) nonwords are reported, where the position of the phonemes that list items
      shared was manipulated (i.e., shared vowel and final consonant [_VC; Experiment
      1], initial consonant and vowel [CV_; Experiment 2], or the two consonants [C_C;
      Experiment 3]. The results show that the position of common phonemes in nonwords
      has differential effects on order and item information. The findings are
      discussed in relation to previous research into the effect of phonemic similarity
      on nonword recall, and modifications to current short-term memory models are
      proposed.

PMID- 16627358
TI  - Inference-driven attention in symbolic and perceptual tasks: biases toward
      expected and unexpected inputs.
AB  - The aims of this paper are (a) to gather support for the hypothesis that some
      basic mechanisms of attentional deployment (i.e., its high efficiency in dealing
      with expected and unexpected inputs) meet the requirements of the inferential
      system and have possibly evolved to support its functioning, and (b) to show that
      these orienting mechanisms function in very similar ways in two perceptual tasks
      and in a symbolic task. The general hypothesis and its predictions are sketched
      in the Introduction, after a discussion of current findings concerning visual
      attention and the generalities of the inferential system. In the empirical
      section, three experiments are presented where participants tracked visual
      trajectories (Experiments 1 and 3) or arithmetic series (Experiments 2 and 3),
      responding to the onset of a target event (e.g., to a specific number) and to the
      repetition of an event (e.g., to a number appearing twice consecutively). Target
      events could be anticipated when they were embedded in regular
      series/trajectories; they could be anticipated, with the anticipation later
      disconfirmed, when a regular series/trajectory was abruptly interrupted before
      the target event occurred; and they could not be anticipated when the
      series/trajectory was random. Repeated events could not be anticipated. Results
      show a very similar pattern of allocation in tracking visual trajectories and
      arithmetic series: Attention is focused on anticipated events; it is defocused
      and redistributed when an anticipation is not confirmed by ensuing events;
      however, performance decreases when dealing with random series/trajectory--that
      is, in the absence of anticipations. In our view, this is due to the fact that
      confirmed and disconfirmed anticipations are crucial events for "knowledge
      revision"--that is, the fine tuning of the inferential system to the environment;
      attentional mechanisms have developed so as to enhance detection of these events,
      possibly at all levels of inferential processing.

PMID- 16627360
TI  - Exercise training produces nonuniform increases in arteriolar density of rat
      soleus and gastrocnemius muscle.
AB  - OBJECTIVE: Exercise training has been shown to increase regional blood flow
      capacity to muscle tissue containing fibers that experience increased activity
      during exercise. The purpose of this study was to test the hypothesis that the
      increased blood flow capacity is partially the result of increases in arteriolar
      density (number of arterioles/mm2 of tissue), specifically in skeletal muscle
      tissue, with the largest relative increase in muscle fiber activity during
      training bouts. METHODS: This hypothesis was tested by comparing and contrasting
      the effects of endurance exercise training (ET) and interval sprint training
      (IST) on arteriolar density in soleus muscle (S) red (Gr) and white (Gw) portions
      of gastrocnemius muscle of male Sprague Dawley rats. ET rats completed 10 weeks
      of treadmill training 30 m/min, 15% grade, 60 min/day, 5 days/week, while IST
      rats completed 10 weeks of IST consisting of six 2.5-min exercise bouts, with 4.5
      min rest between bouts (60 m/min, 15% incline), 5 days/week. The hypothesis would
      be supported if ET increased arteriolar density in S and Gr and if IST increased
      arteriolar density in Gw. RESULTS: ET increased arteriolar density above values
      of sedentary rats (SED) in both the Gw (ET = 0.93 +/- 0.19 arterioles/microm2;
      SED = 0.44 +/- 0.09 arterioles/microm2) and Gr (ET = 0.97 +/- 0.1
      arterioles/microm2; SED = 0.51 +/- 0.06 arterioles/microm2) muscles, but not in S
      (ET = 1.69 +/- 0.45 arterioles/microm2; SED = 1.51 +/- 0.34 arterioles/microm2)
      muscle. In contrast, IST did not alter arteriolar density in Gw or Gr muscle
      tissue. Although arterial wall thickness was greater in S (3.95 +/- 0.40 microm)
      and Gr (6.24 +/- 0.59 microm) than Gw (2.76 +/- 0.18 microm), neither ET or IST
      altered mean wall thickness in either muscle. CONCLUSION: Increases in blood flow
      capacity produced in Gr and Gw by ET appear to be due in part to increased
      arteriolar density. In contrast, increased arteriolar density does not contribute
      to increased blood flow capacity of Gw in IST rats.

PMID- 16627361
TI  - Myocardial gene expression of angiogenic factors in human chronic ischemic
      myocardium: influence of acute ischemia/cardioplegia and reperfusion.
AB  - OBJECTIVE: Angiogenic therapies in animals have demonstrated the development of
      new blood vessels within ischemic myocardium. However, results from clinical
      protein and gene angiogenic trials have been less impressive. The present study
      aimed to investigate the expression of angiogenic genes in human chronic ischemic
      myocardium and the influence of acute ischemia/cardioplegia and reperfusion on
      their expression. METHODS: Myocardial biopsies were taken from chronic ischemic
      and nonischemic myocardium in 15 patients with stable angina pectoris during
      coronary bypass surgery. Tissue samples were evaluated by oligonucleotide
      microarray and quantitative real-time PCR for the expression of angiogenic
      factors. RESULTS: There was identical baseline expression of VEGF-A and VEGF-C
      mRNA in chronic ischemic myocardium compared with nonischemic myocardium.
      Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in
      nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the
      extracellular matrix around the cardiomyocytes in ischemic myocardium.
      CONCLUSION: These data suggest that the nonconclusive VEGF gene therapy trials
      chronic coronary artery disease was not due to a preexisting upregulation of VEGF
      in chronic ischemic myocardium. There might be room for further therapeutic
      angiogenesis in chronic ischemic myocardium.

PMID- 16627362
TI  - A computer-based method for determination of the cell-free layer width in
      microcirculation.
AB  - OBJECTIVES: The cell-free layer between the erythrocyte column and the vessel
      wall is an important determinant of hydrodynamic resistance in microcirculatory
      vessels. The authors report a method for continuous measurement of the width of
      this layer. METHODS: The light intensity of a linear array of pixels
      perpendicular to the vessel axis is continuously determined from a video image of
      a microcirculatory vessel. A threshold level based on Otsu's method is used to
      establish the interface between the cell-free layer and the erythrocyte column.
      To test the method, video images at 750-4500 frames/s were obtained from venules
      and arterioles in rat spinotrapezius muscle at normal and reduced arterial
      pressures before and after induction of erythrocyte aggregation with Dextran 500.
      The current measurements were compared to manual measurements of the same images.
      RESULTS: Values obtained by the manual and the new methods were in agreement
      within the 95% confidence limit by the Bland-Altman analysis and within 90-95%
      range by the correlation coefficient (R2). The more frequent measurements reveal
      substantial, rapid variations in cell-free layer width and changes in mean values
      with alteration of arterial pressure and red cell aggregability. CONCLUSIONS: A
      new, computer-based technique has been developed that provides measurements of
      rapid, time-dependent variations in the width of the cell-free layer in the
      microcirculation.

PMID- 16627363
TI  - Coronary vasomotor reactivity to endothelin-1 in the prediabetic metabolic
      syndrome.
AB  - OBJECTIVE: The purpose of the present investigation was to test the hypothesis
      that coronary vasoconstrictor responses to endothelin-1 are augmented in the
      prediabetic metabolic syndrome. METHODS: ELISA was used to measure plasma
      endothelin-1 and intracoronary endothelin-1 dose-response experiments were
      conducted in vivo on normal control and high-fat-fed prediabetic dogs.
      Additionally, isolated left circumflex (LCX) coronary arteries and arterioles (<
      160 microm) were used for in vitro functional studies and molecular analyses
      (quantitative real-time PCR and Western blotting). RESULTS: Plasma endothelin-1
      concentrations were not different between control and prediabetic dogs. Coronary
      vasoconstriction to endothelin-1 was similar in control and prediabetic dogs,
      both in vivo and in isolated arterioles. Nonetheless, real-time PCR analysis
      revealed significant decreases in ET(A) receptor transcript levels in LCX
      coronary arteries and arterioles. Also, Western blotting revealed a significant
      decrease in ET(A) receptor protein in LCX coronary arteries. CONCLUSIONS: The
      findings of the present investigation indicate that although ET(A) receptor
      signaling is sensitized by induction of the metabolic syndrome, endothelin
      mediated coronary vasoconstriction does not significantly contribute to coronary
      dysfunction at this early stage of prediabetes.

PMID- 16627364
TI  - Mast cell degranulation alters lymphatic contractile activity through action of
      histamine.
AB  - OBJECTIVE: Mast cells reside in most tissues and in close association with blood
      vessels and nerves, areas where lymphatic vessels are also present. Mast cells
      and lymphatic vessels are two important players in the development of the
      inflammatory process. This study was designed to examine the effects of mast cell
      degranulation on the contractile activity of mesenteric lymphatic vessels.
      METHODS: Lymphatic vessel contractile activity was assessed in vitro by video
      microscopy of the mesentery of cow's milk-sensitized guinea pigs upon application
      of beta-lactoglobulin and compared to the response measured in sham animals.
      RESULTS: Application of 5-10 microM beta-lactoglobulin increased lymphatic vessel
      constriction frequency and decreased constriction amplitude (n = 12). This effect
      was not seen in sham-treated animals (n = 16) and was not due to an increased
      number of mast cells in the mesentery of the milk-sensitized animals, as revealed
      by histological examination. Two known mast cell-derived mediators, histamine and
      thromboxane A2, via stable mimetic U46619 also altered lymphatic pumping in a
      similar manner, but only pretreatment with the histamine H1 receptor antagonist
      pyrilamine (1 microM) could reduce the beta-lactoglobulin-induced response. The
      thromboxane A2 receptor antagonist, SQ 29548, and the 5-lipoxygenase inhibitor,
      caffeic acid, were without significant effect. CONCLUSION: In the in vitro
      mesenteric preparation, mast cell degranulation altered lymphatic contractile
      activity via the release of a mediator suggested to be histamine and the
      subsequent activation of H1 receptors. This action could potentially interfere
      with the expected ability of lymphatic vessels to reduce edema during
      inflammation.

PMID- 16627365
TI  - Clot fragments formed from original thrombus obstruct downstream arteries in the
      ischemic injured brain.
AB  - OBJECTIVE: Embolic occlusion of the middle cerebral artery (MCA) leads to distal
      perfusion deficits as the vessel is recanalized. However, the mechanism for the
      perfusion deficits is not fully understood. The authors examined whether distal
      movement of fragments formed from the original thrombus contributes to the
      perfusion deficits. METHODS: In the first series, they studied whether the
      reduction in perfusion deficits is due to the dissolution of the original clots
      embolized or due to collateral perfusion. In the second series, they studied
      whether fragments formed from the original clots move to distal arterial system.
      In the third series, they studied whether plasminogen activator plays a role in
      the thrombolysis following ischemia. RESULTS: Occlusion of MCA permanently
      resulted in large perfusion deficits in the ipsilateral hemisphere, and these
      perfusion deficits did not change significantly after the occlusion. In contrast,
      perfusion deficits reduced significantly in a model of transient MCA occlusion.
      The numbers of fragments formed from the original clots increased gradually after
      the MCA occlusion in the ischemic injured brain. In addition, expression of
      urokinase plasminogen activator was also upregulated. CONCLUSION: The present
      study thus reveals the mechanisms of the downstream arterial occlusion following
      the dissolution of original thrombus.

PMID- 16627366
TI  - Rho and ROCK signaling in VEGF-induced microvascular endothelial
      hyperpermeability.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) plays an important role in
      the regulation of microvascular permeability under various physiological and
      pathological conditions. The authors tested the hypothesis that the small GTPase
      Rho and its downstream effector ROCK (Rho-associated coiled-coil-containing
      protein kinase) mediate VEGF-induced increases in venular permeability. They also
      investigated myosin light chain (MLC) phosphorylation and actin polymerization,
      two well-characterized targets of the Rho-ROCK pathway that are implicated in the
      regulation of endothelial barrier function. METHODS: The apparent permeability
      coefficient of albumin (P(a)) was measured in intact isolated porcine coronary
      venules and in cultured coronary venular endothelial cell (CVEC) monolayers. RhoA
      activation was determined using a Rhotekin-agarose pull down assay. MLC
      phosphorylation was evaluated by immunoblotting with phospho-specific antibodies,
      and endothelial cellular F-actin was viewed using fluorescence microscopy.
      RESULTS: VEGF increased P(a) in both isolated coronary venules and CVEC
      monolayers. The hyperpermeability response occurred in a similar time course to
      that of Rho activation, MLC phosphorylation, and actin stress fiber formation.
      Selective blockage of ROCK with Y27632 dose-dependently inhibited VEGF-induced
      venular hyperpermeability. Moreover, inhibition of either Rho with exoenzyme C3
      or ROCK with Y-27632 attenuated VEGF-induced increases in permeability, MLC
      phosphorylation, and actin-stress fiber formation in CVEC monolayers.
      CONCLUSIONS: Collectively, these findings suggest that the Rho-ROCK signal
      pathway contributes to VEGF-induced hyperpermeability. Myosin light-chain
      phosphorylation and actin stress fiber formation occur concomitantly with the
      increase in permeability upon VEGF stimulation.

PMID- 16627367
TI  - Changes in capillary shear stress in skeletal muscles exposed to long-term
      activity: role of nitric oxide.
AB  - OBJECTIVE: The purpose of this study was to establish whether suppression of
      angiogenesis by nitric oxide synthase (NOS) inhibition in skeletal muscles
      exposed to long-term activity can be explained by changes in capillary shear
      stress linked to the lack of nitric oxide production. METHODS: Capillary shear
      stress was calculated from diameters (d) and red blood cell velocities (V(rbc))
      measured at rest and after acute contractions in epi-illuminated extensor
      digitorum longus muscles of control rats and those in which ankle flexors had
      been stimulated via implanted electrodes (10 Hz, 8 h x day(-1)) for 2 or 7 days
      without and with inhibition of nitric oxide synthase activity by N(omega)-nitro-L
      arginine (L-NNA, 3-4 mg x day(-1) in drinking water). RESULTS: Neither chronic
      electrical stimulation nor L-NNA treatment altered capillary diameters. Capillary
      V(rbc) and shear stress (SS) were doubled in muscles after 2 days stimulation
      (298 +/- 22 microm x s(-1) and 11.4 +/- 1.0 dyne x cm(-2), respectively, p <
      .005) compared to controls (148 +/- 18 microm x s(-1) and 5.6 +/- 0.8 dyne x cm(
      2)) but normalized after 7 days (153 +/- 27 microm x s(-1) and 6.2 +/- 1.0 dyne x
      cm(-2)), when the capillary bed is known to be enlarged. L-NNA, which increased
      blood pressure in all treated animals, abolished the increase in capillary SS
      after 2 days stimulation and decreased SS after 7 days. CONCLUSIONS: These data
      support a role for NO in the early elevation of capillary shear stress that
      initiates angiogenesis in stimulated muscles, likely via modulation of upstream
      vascular resistance, and could explain the lack of capillary growth in stimulated
      muscles when nitric oxide generation is suppressed.

PMID- 16627368
TI  - Perivascular cells along venules upregulate NG2 expression during microvascular
      remodeling.
AB  - OBJECTIVE: Recently the authors have shown that neuron-glial antigen 2 (NG2) is
      expressed by perivascular cells along arterioles and capillaries, but not along
      venules in quiescent rat mesenteric microvascular networks. To investigate how
      the spatial distribution of this proteoglycan changes during microvascular
      remodeling, the objective of this study was to characterize the expression of NG2
      in adult rat mesenteric microvascular networks undergoing active remodeling.
      METHODS: The distribution of NG2 expression was evaluated in adult rat mesenteric
      microvascular networks. Tissues were harvested from 250 g, female, Sprague-Dawley
      rats at 1, 3, and 5 days poststimulation and double immunolabeled for NG2 and
      CD31 (endothelial cell marker). RESULTS: After 1 day, NG2 expression was observed
      along 27 +/- 11% of network draining venules (14-55 microm) and after 3 days, 59
      +/- 10% of draining venules (13-59 microm) stained positive for the proteoglycan.
      By 5 days poststimulation, the percentage of network draining venules (18-59
      microm) staining positive for NG2 returned to 18 +/- 7%, indicating a
      downregulation of the proteoglycan toward quiescent levels along larger-sized
      venules. CONCLUSIONS: The results suggest that NG2 proteoglycan expression is
      transiently upregulated along venules during microvascular remodeling,
      implicating NG2 as a marker of activated venules.

PMID- 16627369
TI  - An evaluation of conditions that may affect the performance of houseboat exhaust
      stacks in prevention of carbon monoxide poisonings from generators.
AB  - National Institute for Occupational Safety and Health (NIOSH) researchers
      evaluated two exhaust stack designs for reducing carbon monoxide (CO) exposures
      from gasoline-powered generator exhaust on houseboats. Tests were conducted (a)
      after dark, (b) in high-temperature and high-humidity environments, (c) during
      temperature inversions, (d) under various generator loads, and (e) at different
      houseboat trim angles. Two different designs of houseboat exhaust stacks were
      evaluated and compared with the side-exhaust configuration, which is standard on
      many houseboats. The two designs were flagpole and vertical stack. Both exhaust
      stacks performed dramatically better than the standard water level, side-exhaust
      configuration. The highest mean CO concentrations on the upper and lower decks of
      the houseboat with the vertical exhaust stack were 27 ppm and 17 ppm. The highest
      mean CO concentrations on the upper and lower decks of the houseboat with the
      modified flagpole stack were 5 ppm and 2 ppm. These findings are much lower than
      the 67 ppm and 341 ppm for the highest mean CO concentrations found on the upper
      and lower decks of houseboats having the usual side-exhausted configuration. The
      NIOSH evaluation also indicated that high-temperature and high-humidity levels,
      temperature inversions, generator loading, and houseboat trim angles had little
      effect on the exhaust stack performance. It also demonstrated the importance of
      proper design and installation of exhaust stacks to ensure that all exhaust gases
      are released through the stack. Based on the results of this work, NIOSH
      investigators continue to recommend that houseboat manufacturers, rental
      companies, and owners retrofit their gasoline-powered generators with exhaust
      stacks to reduce the hazard of CO poisoning and death to individuals on or near
      the houseboat.

PMID- 16627370
TI  - The correlation between personality type and performance time while wearing a
      respirator.
AB  - Many studies have shown that individuals perform better if not wearing a
      respirator compared with wearing a respirator. This study examined the degree of
      performance reduction attributable to specific dominant character traits. The
      subjects performed on a treadmill at a constant speed and grade resulting in 80
      85% VO(2)max. A modified M40 respirator was used to create three levels of
      inspiratory resistance: 2.8, 16.8, and 27.3 cmH(2)O*(sec/L). The 31 subjects were
      tested using a Myers-Briggs Type Indicator and State-Trait Anxiety Inventory.
      Multiple regressions and an ANOVA were used to test for correlation. When air
      intake is very constricted, the only multiple regression equation that was found
      to be statistically significant was sensing-intuition (how one takes in
      information) and thinking-feeling (how one makes a decision) vs. performance time
      for the highest value of inhalation resistance. A simple linear regression
      between trait anxiety level and performance time was not found to be
      statistically significant for the same highest value of inhalation resistance.

PMID- 16627372
TI  - ACE/AACE consensus conference on the implementation of outpatient management of
      diabetes mellitus: consensus conference recommendations.

PMID- 16627373
TI  - Introductory remarks: diabetes care in America - "a sense of urgency".
AB  - OBJECTIVE: To review the status of diabetes care in America and present questions
      to be addressed in the current consensus conference. METHODS: Data from recent
      studies are reviewed, and trends in diabetes care are summarized in an effort to
      improve interventional strategies and future results. RESULTS: The diabetes
      epidemic is worsening; more than 20 million Americans have diabetes. Another 42
      million Americans have pre-diabetes. Diabetes care in America has deteriorated
      during the past decade, with fewer patients at target hemoglobin A1c levels. New
      diabetes-related therapies and technologies are available, but clinicians often
      fail to intervene early and aggressively to achieve good glycemic control and
      help avoid complications. Moreover, many patients do not receive education and
      training in diabetes self-management. Several questions must be addressed in
      order to develop recommendations for implementing more aggressive treatment
      strategies in patients with diabetes. CONCLUSION: Substantial clinical and
      financial benefits can be gained through better control of diabetes. Finding ways
      to meet this challenge must be a priority.

PMID- 16627374
TI  - Impaired glucose tolerance, diabetes, and cardiovascular disease.
AB  - OBJECTIVE: To analyze the association among impaired glucose tolerance (IGT),
      diabetes, and cardiovascular disease (CVD). METHODS: We review current studies
      that have addressed the foregoing relationship and summarize the results of
      diagnostic and therapeutic interventions. RESULTS: A major cause of the reduction
      in life expectancy in patients with diabetes is CVD and cardiovascular
      complications. Both prediabetes and diabetes predispose to cardiovascular
      alterations. IGT and even the upper normal values of nondiabetic glucose levels
      are associated with an increased cardiovascular risk. The risk of heart disease
      can be increased as early as 15 years before the diagnosis of diabetes. Patients
      with chronic or acute CVD and no previous diagnosis of diabetes frequently
      present with either IGT or diabetes. Thus, such patients should undergo screening
      for diabetes with an oral glucose tolerance test. In acute coronary syndromes,
      lowering of glucose levels to the near-normal range by administration of insulin
      is highly beneficial. Early, rigorous interventions to improve metabolic control
      will yield better cardiovascular outcomes in patients with dysglycemia.
      CONCLUSION: Aggressive preventive and treatment strategies, which can include
      multiple interventions, are needed to minimize the potential effects of CVD in
      patients with diabetes or IGT.

PMID- 16627375
TI  - An update on the Diabetes Prevention Program.
AB  - OBJECTIVE: To summarize the results of the Diabetes Prevention Program (DPP) and
      describe the additional 5-year follow-up study. METHODS: The design,
      implementation, and outcome of the DPP are reviewed, and an economic analysis of
      the effects of diabetes prevention and delay is presented. RESULTS: The DPP, thus
      far the largest diabetes prevention trial with the most ethnically diverse
      patient population, originally consisted of more than 3,800 subjects with
      impaired glucose tolerance. These subjects were randomized to receive one of four
      interventions: intensive lifestyle adjustments or standard lifestyle plus one of
      the following--placebo, metformin, or troglitazone. In June 1998, the
      troglitazone treatment was discontinued after a fatal case of liver failure in a
      study participant, but the subjects in this arm of the study continued to undergo
      followup. Thus, 3,234 subjects remained in the other three arms of the study.
      After a mean of 2.8 years of follow-up, the DPP was prematurely terminated
      because of an observed significant benefit to the intervention groups. Both
      metformin therapy and intensive lifestyle intervention reduced the risk of
      developing diabetes (by 31% and 58%, respectively, in comparison with placebo),
      and both interventions were deemed to be cost-effective on the basis of computer
      projections over a lifetime. Because of the premature discontinuation of the DPP,
      the durability of the interventions on diabetes prevention and the effect on
      microvascular and macrovascular disease could not be assessed. The subsequent
      outcomes study will address these issues during a 5-year follow-up period.
      CONCLUSION: The DPP showed that both metformin and intensive lifestyle
      modifications effectively delayed or prevented the development of diabetes in a
      cost-effective manner.

PMID- 16627376
TI  - Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease
      in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin
      Dependent Diabetes Mellitus (STOP-NIDDM) Trial.
AB  - OBJECTIVE: To evaluate, in subjects with impaired glucose tolerance (IGT), the
      effect of acarbose on the incidence of diabetes, hypertension, and cardiovascular
      disease. METHODS: The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus
      (STOP-NIDDM) Trial was an international, multicenter, double-blind, placebo
      controlled, randomized investigation, undertaken in 9 participating countries
      from December 1995 through August 2001. Patients were randomly assigned to
      receive placebo (N = 715) or acarbose, 100 mg three times a day (N = 714), and
      underwent follow-up for a mean of 3.3 years. Sixty-one subjects (4%) were
      excluded from the study because they did not have IGT or had no postrandomization
      data; thus, 1,368 subjects remained for intent-to-treat analysis. The outcome
      measures were the development of diabetes based on a single oral glucose
      tolerance test, the development of hypertension ((3) 140/90 mm Hg), and the
      development of major cardiovascular events, including coronary heart disease,
      cardiovascular death, stroke, and peripheral vascular disease. RESULTS: Two
      hundred eleven subjects in the acarbose-treated group and 130 in the placebo
      group discontinued treatment prematurely; however, they underwent follow-up for
      assessment of end points. Acarbose treatment resulted in a 25% relative risk
      reduction in the development of type 2 diabetes (hazards ratio [HR], 0.75; 95%
      confidence interval [CI], 0.63 to 0.90; P = 0.0015), in a 34% risk reduction in
      the development of new cases of hypertension (HR, 0.66; 95% CI, 0.49 to 0.89; P =
      0.0059), and in a 49% risk reduction in the development of cardiovascular events
      (HR, 0.51; 95% CI, 0.28 to 0.95; P = 0.03). A post hoc cost-effectiveness
      analysis done from the Swedish perspective showed that acarbose treatment was
      likely to be cost-effective in the management of subjects with IGT. CONCLUSION:
      The STOP-NIDDM Trial demonstrated that, in subjects with IGT, acarbose treatment
      was effective in reducing the risk of type 2 diabetes. It also suggested that it
      was associated with a reduction in hypertension and cardiovascular disease.

PMID- 16627377
TI  - Analysis of the XENDOS study (Xenical in the Prevention of Diabetes in Obese
      Subjects).
AB  - OBJECTIVE: To present an overview and analysis of the previously published XENDOS
      (Xenical in the Prevention of Diabetes in Obese Subjects) study. METHODS: The
      design, methods, and results of the XENDOS study are reviewed. On the basis of
      the findings, conclusions are discussed. RESULTS: The XENDOS study was a double
      blind, prospective investigation with 3,305 participants, who had either normal
      or impaired glucose tolerance. The patients were randomly assigned to lifestyle
      plus placebo intervention or lifestyle changes plus orlistat (Xenical) (120 mg 3
      times daily). After 4 years of treatment, the cumulative incidence of type 2
      diabetes was 9.0% in the placebo group and 6.2% in the orlistat group (P =
      0.0032). The incidence of diabetes was low and not significantly different in the
      two treatment arms of the study in those patients with normal glucose tolerance
      at baseline. In patients with impaired glucose tolerance, however, the conversion
      to type 2 diabetes was significantly greater in the placebo group than in the
      orlistat-treated group (P = 0.0024). Division of the baseline fasting plasma
      glucose levels into an upper and a lower subclassification revealed a significant
      difference (P < 0.05) in incidence of diabetes between the placebo (17.8%) and
      orlistat (9.4%) groups in the upper stratification but no significant difference
      in the lower subclassification (3.2% versus 2.5%, respectively). The weight loss
      was significantly greater in the orlistat group than in the placebo group for the
      entire study period (P < 0.001). CONCLUSION: In the XENDOS study, orlistat
      therapy reduced the incidence of diabetes beyond the result achieved with
      lifestyle changes only, an effect that was especially evident in patients with
      baseline impairment of glucose tolerance.

PMID- 16627378
TI  - Insights from the diabetes control and complications trial/epidemiology of
      diabetes interventions and complications study on the use of intensive glycemic
      treatment to reduce the risk of complications of type 1 diabetes.
AB  - OBJECTIVE: To analyze the long-term effects of early implementation of intensive
      glycemic treatment in patients with type 1 diabetes. METHODS: Data from the
      Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes
      Interventions and Complications (EDIC) followup study are reviewed, particularly
      in terms of reduction of diabetes-related complications. RESULTS: In the DCCT,
      intensive intervention resulted in a 63% reduction in retinopathy progression, a
      47% decrease in development of severe nonproliferative diabetic retinopathy, a
      39% and 54% reduction in microalbuminuria and macroalbuminuria, respectively, and
      a 60% reduction in clinical neuropathy at 5 years. Aggressive early intervention
      before the manifestation of complications yielded the best results. In both
      intensive and conventional treatment groups in the DCCT, there was approximately
      a 40% reduction in risk of progression of retinopathy for each 10% proportional
      reduction in hemoglobin A1c (HbA1c). At the conclusion of the DCCT, participants
      learned about the results, and all were encouraged and helped to adopt intensive
      treatment. Thereafter, the HbA1c levels of the two groups rapidly approached each
      other and have not been significantly different for the past 5 years of the EDIC
      study. CONCLUSION: The findings in the DCCT and the EDIC follow-up study support
      early intensive treatment in patients with type 1 diabetes, with the goal of
      maintaining HbA1c levels as close to normal as is safely possible, to achieve
      long-term beneficial effects on the risk of complications.

PMID- 16627379
TI  - Contributions of fasting and postprandial glucose to hemoglobin A1c.
AB  - OBJECTIVE: To define the respective contributions of fasting and postprandial
      plasma glucose to hemoglobin A1c (HbA1c) in patients with non-insulin-treated
      type 2 diabetes. METHODS: Previous studies of diurnal glycemic profiles are
      reviewed, and glucose values for predicting successful treatment of diabetes are
      suggested. RESULTS: By analyzing the results from prior studies of diurnal
      glycemic profiles, we found that the relative contribution of postprandial plasma
      glucose was high (70%) in patients with fairly good control of diabetes (HbA1c
      <7.3%) and decreased progressively (30%) with worsening diabetes (HbA1c >10.2%).
      In contrast, the contribution of fasting plasma glucose showed a gradual increase
      with increasing levels of HbA1c. By using the same model (the diurnal glycemic
      profile), we established that post-meal glycemia was a better predictor of good
      or satisfactory control of diabetes (HbA1c <7%) than was fasting glucose. The
      best cutoff values that ensured the optimal balance between high sensitivity and
      specificity were approximately 200 mg/dL at 11 AM and 160 mg/dL at 2 PM. The cut
      point values for predicting treatment success (specificity (3) 90%) were 162
      mg/dL at 11 AM and 126 mg/dL at 2 PM. CONCLUSION: Postprandial plasma glucose is
      the predominant contributor in patients with satisfactory to good control of
      diabetes, whereas the contribution of fasting plasma glucose increases with
      worsening diabetes. Postmeal thresholds for predicting good or satisfactory
      control of diabetes are dependent on the timing of the meals.

PMID- 16627380
TI  - Postprandial hyperglycemia and cardiovascular disease.
AB  - OBJECTIVE: To review the role of postprandial hyperglycemia in the development of
      type 2 diabetes mellitus and cardiovascular disease. METHODS: The pathogenic
      mechanisms involved in the deterioration of glucose tolerance are discussed, and
      findings from relevant epidemiologic and clinical interventional studies are
      presented. RESULTS: It is now well established that hyperglycemia is an
      independent risk factor for cardiovascular disease, with no apparent threshold.
      In clinical practice, glycemic exposure is measured by hemoglobin A1c levels.
      These values reflect the contribution of fasting and postprandial plasma glucose
      levels during the previous 2 to 3 months. Epidemiologic studies have indicated
      that, at hemoglobin A1c levels (5.5%) already associated with a substantially
      increased risk for cardiovascular mortality, fasting plasma glucose levels are
      generally normal. These observations implicate isolated postprandial
      hyperglycemia as a cardiovascular risk factor. Controlled interventional clinical
      trials have found that reduction of postprandial hyperglycemia decreases
      cardiovascular events or surrogates thereof. CONCLUSION: Postprandial
      hyperglycemia should be considered a cardiovascular risk factor similar to
      hypertension, hyperlipidemia, and smoking; accordingly, it should be monitored
      and treated.

PMID- 16627381
TI  - Can glycemic targets be achieved-- in particular with two daily injections of a
      mix of intermediate- and short-acting insulin?
AB  - OBJECTIVE: To present data that demonstrate the feasibility of using twice-daily
      insulin injections, in combination with selected orally administered agents, to
      achieve glycemic targets in patients with type 2 diabetes. METHODS: Recent
      studies of the effects of various therapeutic strategies in patients with type 2
      diabetes are reviewed, and the rationale for and recommended approaches in the
      use of combination treatment to achieve glycemic goals are discussed. RESULTS:
      The combination of insulin and insulin sensitizers is an effective option for
      achieving glycemic goals (hemoglobin A1c pound 6.5%). Although thiazolidinediones
      are better sensitizers than metformin, they are associated with significant
      weight gain. In contradistinction, metformin, an effective insulin sensitizer,
      causes less weight gain. The sequence in which these two sensitizers are added to
      insulin therapy is important; if metformin is added before a thiazolidinedione,
      weight gain may be avoided. CONCLUSION: Glycemic targets can be achieved with use
      of twice-daily mixtures of intermediate- and short-acting insulin in a high
      percentage of patients with type 2 diabetes.

PMID- 16627382
TI  - Treatment of impaired glucose tolerance with acarbose and its effect on intima
      media thickness: a substudy of the STOP-NIDDM trial (study to prevent non-insulin
      dependent diabetes mellitus).
AB  - OBJECTIVE: To discuss the influence of glucose excursions on intima-media
      thickness (IMT) and the potential benefits of treatment to reduce or reverse its
      effects on cardiovascular risk. METHODS: The findings in pertinent reported
      studies are reviewed, and the efficacy of various interventions for management of
      impaired glucose tolerance and type 2 diabetes in slowing the progression of IMT
      is analyzed. RESULTS: Considerable evidence from published epidemiologic studies
      provides compelling data regarding the association between postprandial and
      postchallenge glycemic excursions and cardiovascular risk. IMT has been shown to
      be a good surrogate marker for symptomatic and coronary atherosclerosis. Acarbose
      treatment in patients with impaired glucose tolerance has been shown to diminish
      the progression of IMT in comparison with placebo. In a study of repaglinide or
      glyburide therapy in patients with type 2 diabetes, a reduction in IMT was noted
      in the repaglinide group but not in the glyburide group at 1-year follow-up.
      CONCLUSION: Measurement of IMT allows direct observation of vascular damage
      attributable to postprandial and postchallenge hyperglycemia. It also provides a
      means for direct assessment of the effect of medications used for the control of
      glucose excursions.

PMID- 16627383
TI  - Oxidative stress and diabetes-associated complications.
AB  - OBJECTIVE: To review the role of oxidative stress in the development of
      complications of diabetes. METHODS: Evidence that implicates hyperglycemia
      derived oxygen free radicals as mediators of diabetes-associated complications is
      presented and discussed. RESULTS: Recent studies have indicated that a
      hyperglycemia-induced overproduction of superoxide seems to be the first and main
      event in the activation of all pathways involved in the pathogenesis of
      complications of diabetes. Superoxide overproduction is accompanied by increased
      generation of nitric oxide and, consequently, formation of the strong oxidant
      peroxynitrite and by poly(adenosine diphosphate-ribose) polymerase activation,
      which in turn further activates the pathways involved in the pathogenesis of
      diabetes-related complications. This process results in acute endothelial
      dysfunction and activation of inflammation in blood vessels of patients with
      diabetes, and these factors contribute to the development of complications of
      diabetes. CONCLUSION: In vivo evidence supports the major contribution of
      hyperglycemia in producing oxidative stress and, ultimately, acute endothelial
      dysfunction in blood vessels of patients with diabetes.

PMID- 16627384
TI  - Tackling hyperglycemia: a more comprehensive approach.
AB  - OBJECTIVE: To review the components of glycemic control in patients with diabetes
      and discuss the factors contributing to development of complications. METHODS:
      The findings in various published reports are summarized, particularly in
      reference to metabolic alterations, treatment, and long-term outcomes in
      diabetes. RESULTS: Hemoglobin A1c, an integrated marker of overall glucose
      exposure, is the standard for monitoring glycemic control. The results in the
      United Kingdom Prospective Diabetes Study indicated that each 1% decrease in
      hemoglobin A1c reduced the risk for mortality associated with diabetes by 21% and
      the risk for myocardial infarction by 14%. Nevertheless, fasting plasma glucose
      and postprandial glucose levels are well-defined targets for therapy. Numerous
      epidemiologic studies also support the concept that excessive glucose excursion
      after ingestion of an oral glucose load is associated with an independent risk
      for cardiovascular disease that is greater than the one associated with the
      fasting plasma glucose level. Hyperglycemia apparently activates different
      metabolic pathways that may contribute to development of microangiopathy and
      macroangiopathy. Intensive treatment to maintain strict glycemic control has been
      shown to yield better control of diabetes-related complications in comparison
      with conventional therapy. CONCLUSION: The complexity of the metabolic
      alterations in diabetes must be fully recognized, and a comprehensive approach to
      management should be considered.

PMID- 16627385
TI  - Assessing the preprandial glucose target: 100 mg/dL versus 110 mg/dL.
AB  - OBJECTIVE: To assess the potential value of lowering the impaired fasting glucose
      (IFG) cut point from 110 mg/dL to 100 mg/dL. METHODS: Data from pertinent
      published studies are analyzed in an effort to identify the risk of diabetes,
      cardiovascular disease, and mortality under various glycemic conditions. RESULTS:
      The risk of developing diabetes increases with advancing age. The relationship is
      strongest when the 2-hour plasma glucose level is analyzed, whereas the fasting
      plasma glucose level is generally stable and changes little with aging. The 2
      hour plasma glucose level has a linear relationship with cardiovascular disease
      and mortality. Most patients with acute myocardial infarction have high 2-hour
      plasma glucose levels but normal fasting plasma glucose values. Increased
      mortality risk based on the fasting plasma glucose level does not appear until
      values of approximately 7 mmol/L (126 mg/dL) and remains relatively flat at lower
      levels. CONCLUSION: Lowering the cut point for IFG from 6.1 mmol/L to 5.6 mmol/L
      (110 mg/dL to 100 mg/dL) increases the prevalence of IFG but does not predict
      mortality below 7 mmol/L (126 mg/dL).

PMID- 16627386
TI  - The Treat-to-Target Trial and related studies.
AB  - OBJECTIVE: To describe the rationale for, and the findings of, the Treat-to
      Target Trial and to compare its results with those of two subsequent studies
      based on the same concepts. METHODS: The 24-hour pattern of hyperglycemia in type
      2 diabetes is presented, and its separate components are identified in an attempt
      to help optimize therapeutic interventions for diabetes. In addition, the treat
      to-target concept, including glycemic outcomes and potential adverse effects, is
      discussed. RESULTS: Using a hemoglobin A1c (A1c) value of 7% as a treatment goal
      based on evidence from interventional studies and a fasting plasma glucose level
      of 100 mg/dL as a target for titration of dosage of basal insulin, the Treat-to
      Target Trial tested two hypotheses. It confirmed that addition of basal insulin
      to previously unsuccessful oral therapies can, using a simple algorithm, restore
      glycemic control to 7% A1c or better in most patients with type 2 diabetes. It
      also confirmed that a long-acting insulin analogue, glargine, causes less
      hypoglycemia than human NPH insulin when used in this way. Two subsequent studies
      using similar treatment algorithms showed comparable ability to improve glycemic
      control but also demonstrated more frequent unwanted effects of insulin treatment
      when a different comparator regimen was used to initiate therapy than when a
      glargine-based regimen was used. CONCLUSION: Initiation of insulin therapy with
      structured titration to glycemic targets can frequently, but not always, restore
      glycemic control in patients with type 2 diabetes when orally administered agents
      are no longer successful alone. Future trials should include hypoglycemia and
      weight gain as specific, objectively measured endpoints to assess their
      importance as adverse effects of titrating insulin dosage to target. Studies are
      needed to assess ways to control postprandial as well as basal hyperglycemia and
      thus enable almost all patients with type 2 diabetes to reach A1c targets.

PMID- 16627387
TI  - Long-term intervention studies using insulin in patients with type 1 diabetes.
AB  - OBJECTIVE: To discuss data from long-term intervention studies regarding therapy
      in type 1 diabetes and review strategies for preventing hypoglycemia and safely
      achieving glycemic goals in this patient population. METHODS: The shortcomings of
      traditional models of insulin therapy are elucidated, and the need for
      physiologic insulin replacement is emphasized. RESULTS: An estimated more than 10
      million patients will have type 1 diabetes worldwide within the next 20 years.
      Twice-daily injection of premixed or self-mixed insulin is the most common
      insulin regimen; however, this therapeutic strategy is also a major contributor
      to hypoglycemia and, eventually, hypoglycemia unawareness. Hypoglycemia
      unawareness in patients with type 1 diabetes has been found to be largely
      reversible. Moreover, intensive insulin therapy may prevent hypoglycemia and
      maintain glycemic targets. The most physiologic regimen of insulin available is
      continuous subcutaneous insulin infusion with an insulin pump; however, insulin
      glargine is a useful alternative to pump therapy. CONCLUSION: Use of today's
      rapid- and long-acting insulin analogues in intensive management protocols not
      only improves glycemic control but also reduces the risk of hypoglycemia.
      Therefore, safe achievement and maintenance of target glycemic goals are
      possible.

PMID- 16627388
TI  - Control of cardiovascular risk factors in the Veterans Affairs Diabetes Trial in
      advanced type 2 diabetes.
AB  - OBJECTIVE: To present a status report on the Veterans Affairs Diabetes Trial
      (VADT), a multisite long-term study examining the effect of glucose control on
      cardiovascular (CV) complications in older patients with established, poorly
      controlled type 2 diabetes. METHODS: We review the rationale, objectives, and
      design of the VADT and summarize the baseline data and the results achieved thus
      far. RESULTS: The main objective of this 20-site, 1,792-patient study is to
      ascertain whether intensive glucose control can reduce major CV events in
      patients with difficult-to-control type 2 diabetes. The study design consists of
      a standard treatment arm and an intensive treatment arm, with a goal of 1.5%
      difference in hemoglobin A1c values between the two groups. The trial is now in
      its fifth year, with completion expected in December 2007. The planned glucose
      separation has been achieved and maintained to this point. Blood pressure and
      hemoglobin A1c levels have been reduced from baseline values, and established CV
      risk factors are within recommended ranges. CONCLUSION: The current results of
      the VADT show that excellent control of glucose and CV risk factors can be
      achieved and maintained in the population studied. The results of these
      interventions on CV outcomes will ultimately have important implications for the
      clinical care of older patients with advanced type 2 diabetes.

PMID- 16627389
TI  - Glycemic control and prevention of microvascular and macrovascular disease in the
      Steno 2 study.
AB  - OBJECTIVE: To review key findings and insights from the Steno 2 trial involving
      160 patients with type 2 diabetes in Denmark. METHODS: The Steno 2 study design,
      with conventional and intensive treatment arms, is described, and the outcomes
      are summarized. RESULTS: Intensive and target-driven behavior modeling and
      polypharmacy for 7.8 years induced an absolute risk reduction of 20% in
      cardiovascular disease events in patients with type 2 diabetes and the metabolic
      syndrome in comparison with a conventional multifactorial treatment. The relative
      risk reduction found for microvascular events after 4 years was maintained at a
      similar level after 7.8 years of intervention: nephropathy 61%, retinopathy 58%,
      and autonomic neuropathy 63%. CONCLUSION: Improving glycemic control in patients
      with type 2 diabetes may be as important as, or even more important than,
      treating hypertension and dyslipidemia for the prevention of both microvascular
      and macrovascular complications, particularly when aggressive treatment is
      initiated at an early stage of the disease.

PMID- 16627390
TI  - How can we implement current therapies and interventions to achieve glycemic
      control?
AB  - OBJECTIVE: To discuss the appropriate use of oral therapies to achieve and
      sustain glycemic targets in patients with type 2 diabetes. METHODS: The stages in
      the development and progression of type 2 diabetes are reviewed, and the
      limitations of single-drug therapy are addressed. RESULTS: The development of
      diabetes is a staged progression; affected patients show evolution through
      numerous stages of glucose intolerance before clinical diabetes manifests. Beta
      cell function continues to deteriorate until absolute failure occurs; however,
      other factors, such as glucose and lipid toxicities, insulin resistance in
      peripheral tissues, and loss of the first-phase insulin response, further impair
      the body's ability to regulate release of insulin in response to glucose.
      Traditional treatment algorithms often fail to address the progressive,
      multifaceted nature of type 2 diabetes, with its numerous related abnormalities.
      Combination therapy with orally administered agents can be used to manage glucose
      concentrations and other risk factors safely and effectively. CONCLUSION: The
      therapeutic goal in type 2 diabetes is to achieve and maintain a physiologic
      profile as close to normal as possible. This outcome necessitates treatment of
      multiple defects with use of various combinations of orally administered agents.
      Clinicians should focus on effective treatment of these defects to achieve
      established targets.

PMID- 16627391
TI  - Treatment models from the International Diabetes Center: advancing from oral
      agents to insulin therapy in type 2 diabetes.
AB  - OBJECTIVE: To discuss treatment models used at the International Diabetes Center
      (IDC) and present strategies for transitioning patients with type 2 diabetes from
      orally administered medications to insulin therapy. METHODS: The experiences of
      the IDC in developing and improving patient care and educational programs are
      reviewed. In addition, clinical outcomes and economic results are highlighted.
      RESULTS: In the management of chronic conditions such as diabetes, the patient is
      a crucial member of the health-care team. Therefore, patients must understand and
      endorse treatment goals. Key components of the patient-centered IDC treatment
      model are group instruction focused on behavioral change, worksite education and
      coaching programs, and treatment algorithms to help clinicians identify treatment
      priorities and initiate appropriate therapeutic strategies, including early and
      more effective use of insulin therapy. CONCLUSION: The IDC patient-centered team
      model aimed at helping patients live well with diabetes has been shown to improve
      achievement of glycemic, lipid, and blood pressure goals, and it is economically
      viable. One approach to helping more patients with type 2 diabetes reach glycemic
      targets is for clinicians to become more comfortable with, and therefore more
      aggressive in, initiating and adjusting insulin therapy.

PMID- 16627392
TI  - Insulin treatment in type 1 diabetes.
AB  - OBJECTIVE: To present key aspects and strategies for use of insulin therapy in
      patients with type 1 diabetes mellitus. METHODS: Limitations and advantages of
      various insulin regimens are discussed, and issues pertaining to insulin
      analogues are reviewed. RESULTS: Rapid-acting insulin analogues provide better
      and safer postprandial glucose coverage than does human regular insulin. Premixed
      insulin preparations do not provide the flexibility to address the individual
      needs of patients adequately to control postprandial glucose excursions. Because
      of its peak, short duration, and high variability, NPH insulin is inappropriate
      for patients with type 1 diabetes and patients with type 2 diabetes who require
      continuous basal coverage. Continuous infusion of soluble insulin by means of an
      insulin pump is currently the most physiologic approach available for treatment
      of type 1 diabetes. Use of insulin glargine or insulin detemir with a rapid
      acting insulin analogue at meals is an effective and reasonable alternative to
      insulin pump therapy. CONCLUSION: Both rapid-acting and long-acting insulin
      analogues improve glycemic control. This improvement involves controlling
      hemoglobin A1c levels, reducing glucose excursions, and decreasing hypoglycemia,
      particularly during the night. Clinicians should prescribe insulin regimens that
      yield physiologic results in patients with type 1 diabetes.

PMID- 16627394
TI  - Changing patient behavior.
AB  - OBJECTIVE: To discuss barriers and strategies relevant to initiating lifestyle
      modifications for the prevention and treatment of type 2 diabetes. METHODS:
      Findings from previously published studies are reviewed. In light of reported
      successful changes in patient behavior and resultant improved outcomes pertinent
      to reduction or control of diabetes, methods to achieve optimal results are
      outlined. RESULTS: Both the Diabetes Prevention Program and the Finnish Diabetes
      Prevention Study demonstrated that intensive lifestyle interventions, such as
      weight loss as a result of physical activity, can delay and prevent the
      development of type 2 diabetes. Key barriers to initiating behavioral
      modifications in patients include the following: (1) health-care provider
      experience, (2) patient experience and beliefs, (3) lack of health-care system
      support, and (4) minimal availability of community support. These barriers can be
      overcome through use of proven strategies--promoting patient awareness of health
      risks, selecting patients who are willing to participate in a behavioral
      modification program, defining realistic goals, establishing patient
      accountability, and maintaining regular follow-up for review of progress,
      providing assistance with problem solving, and reinforcement of efforts and
      successes. CONCLUSION: The feasibility of initiating successful lifestyle
      interventions has been shown in numerous studies. The effective implementation of
      these interventions in clinical practice will necessitate fundamental changes in
      the health-care system and society in general.

PMID- 16627393
TI  - Role of self-monitoring of blood glucose in glycemic control.
AB  - OBJECTIVE: To examine the role of self-monitoring of blood glucose (SMBG) in the
      management of diabetes mellitus. METHODS: Current trends and published evidence
      are reviewed. RESULTS: Despite the widespread evidence that lowering glycemic
      levels reduces the risks of complications in patients with diabetes, little
      improvement in glycemic control has been noted among patients in the United
      States and Europe in recent years. Although SMBG has been widely used,
      considerable controversy surrounds its role in achieving glycemic control. The
      high cost of test strips has made considerations regarding appropriate
      recommendations for SMBG a priority, especially in light of the current climate
      of health-care cost-containment. Existing clinical recommendations lack specific
      guidance to patients and clinicians regarding SMBG practice intensity and
      frequency, particularly for those patients not treated with insulin. Previous
      studies of the association between SMBG and glycemic control often found weak and
      conflicting results. CONCLUSION: A reexamination of the role of SMBG is needed,
      with special attention to the unique needs of patients using different diabetes
      treatments, within special clinical subpopulations, and during initiation of SMBG
      versus its ongoing use. Further understanding of the intensity and frequency of
      SMBG needed to reflect the variability in glycemic patterns would facilitate more
      specific guideline development. Educational programs that focus on teaching
      patients the recommended SMBG practice, specific glycemic targets, and
      appropriate responses to various blood glucose readings would be beneficial.
      Continuing medical education programs for health-care providers should suggest
      ways to analyze patient SMBG records to tailor medication regimens. For transfer
      or communication of SMBG reports to the clinical staff, a standardized format
      that extracts key data elements and allows quick review by health-care providers
      would be useful. Because the practice of SMBG is expensive, the cost
      effectiveness of SMBG needs to be carefully assessed.

PMID- 16627395
TI  - Diets do not fail: the success of medical nutrition therapy in patients with
      diabetes.
AB  - OBJECTIVE: To emphasize the importance of medical nutrition therapy in the
      overall management of diabetes. METHODS: Published reports of the effectiveness
      of nutrition intervention in glycemic control are reviewed, and useful strategies
      for implementation of lifestyle changes in patients with diabetes are discussed.
      RESULTS: In randomized controlled trials of nutrition therapy in patients with
      diabetes, reduction in hemoglobin A1c levels has been demonstrated. The focus of
      medical nutrition intervention in patients with diabetes should be strategies
      that will address the metabolic abnormalities of glucose, lipids, and blood
      pressure associated with this disease. Early referral for lifestyle changes and
      advice will yield the most benefit in prevention of development of type 2
      diabetes or minimization of progression of the disease if the diagnosis has
      already been made. Patients should be educated about the progressive nature of
      type 2 diabetes and the importance of glycemic control, with appropriate food
      choices and physical activity in conjunction with their antidiabetes medication.
      CONCLUSION: The health-care team can provide practical and useful information to
      patients with diabetes that will improve management of their disease and enhance
      their well-being.

PMID- 16627396
TI  - Implementing diabetes self-management training programs: breaking through the
      barriers in primary care.
AB  - OBJECTIVE: To review issues, examples, and recommendations for the delivery of
      diabetes self-management training (DSMT) services in the primary care setting.
      METHODS: Barriers to provision of DSMT at the point of care and strategies to
      overcome such challenges are discussed. In addition, new avenues to support
      continuing diabetes education are presented. RESULTS: Diabetes is a complex
      disease that requires education, monitoring, and medication adjustment to achieve
      treatment goals. Unfortunately, adequate support is seldom available for the
      increased time and effort needed for optimal management of diabetes. Health-care
      delivery systems are designed to provide a response to acute illnesses and are
      poorly configured to meet the needs of patients with complex chronic illnesses.
      Although team care and DSMT have proved to be effective, they have infrequently
      been integrated in primary care offices, where most patients with diabetes
      receive treatment. It is encouraging that the studies conducted to date have
      generally found office-based counseling and educational strategies to be
      effective for the vast majority of patients with diabetes. Community-based
      programs that extend DSMT have also been successful. CONCLUSION: Diabetes is a
      chronic disease that requires providers to deliver multifaceted care and patients
      to be proficient in many self-care skills. Team care and DSMT approaches have
      been found to yield beneficial results, yet such strategies are seldom used in
      the primary care office. Thus, models that support the team approach to delivery
      of diabetes care and self-management education interventions should be explored
      and encouraged.

PMID- 16627397
TI  - Internet resources to improve health care for patients with diabetes.
AB  - OBJECTIVE: To review diabetes-related Web sites and online resources for health
      care professionals, patients, and health-care organizations. METHODS: Diabetes
      related Web sites were sought and reviewed. RESULTS: The Internet has a vast
      amount of diabetes-related content. Many health-care organizations make their
      practice guidelines available for online viewing, downloading, or both. Other
      resources focus on helping clinicians answer specific clinical questions at the
      point of care by providing extensive diabetes-related basic science, diagnostic,
      and therapeutic content. Some online resources can help to improve patient
      adherence to recommended treatment regimens and healthier lifestyles. New Web
      sites and online tools can help health-care professionals and organizations
      implement improved systems of diabetes care, focusing on evidence-based decision
      making, effective information systems, and meeting the needs of diverse
      populations. Online data can also help those wishing to purchase and implement
      electronic registries or electronic medical record systems (or both) to compare
      product characteristics. CONCLUSION: An increasing number of diabetes-related Web
      sites have become available to help clinicians, patients, and health-care systems
      obtain the information, tools, and support to address the many challenges
      involved in effective management of diabetes.

PMID- 16627398
TI  - Diabetes educators: partners in diabetes care and management.
AB  - OBJECTIVE: To promote the role of the diabetes educator as an important team
      member in conjunction with the patient and other clinicians in optimizing
      diabetes management. METHODS: The goal of the diabetes educator in facilitating
      changes in patient behavior is reviewed, and current trends and strategies for
      improvement of outcomes by means of diabetes education are outlined. RESULTS: The
      American Association of Diabetes Educators (AADE) is a multidisciplinary group of
      healthcare professionals dedicated to the professional growth and development of
      personnel who are responsible for diabetes education. Diabetes management is best
      addressed by using a team approach in a patient-centered care environment.
      Diabetes education encompasses more than the dissemination of information; the
      goal is to facilitate changes in specific behaviors relating to both therapy and
      lifestyle that support good diabetes management and improved clinical outcomes.
      Diabetes educators currently frame their intervention on the basis of the AADE 7
      Self-Care Behaviors: (1) healthful eating, (2) being active, (3) monitoring, (4)
      taking medication, (5) problem-solving, (6) healthful coping, and (7) reducing
      risks. Diabetes education is underutilized; approximately 60% to 70% of patients
      with diabetes have not received training in diabetes self-management. Diabetes
      educators are trained to identify and help overcome barriers to optimal diabetes
      care. CONCLUSION: Individual patients and the overall health-care system will
      benefit when physicians and other health-care providers collaborate with diabetes
      educators to ensure that patients receive the information, training, and support
      needed to facilitate effective diabetes self-management.

PMID- 16627399
TI  - Therapeutic options in development for management of diabetes: pharmacologic
      agents and new technologies.
AB  - OBJECTIVE: To review new pharmacologic therapies and technologies relevant to the
      management of diabetes and its complications. METHODS: New treatment options for
      diabetes, made available through research efforts during the past 2 decades, are
      discussed. RESULTS: Several new drugs and drug classes for the management of
      diabetes are under development, including the incretin mimetic agents (exenatide,
      dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 analogues), the
      amylin analogue pramlintide, the cannabinoid-1 receptor antagonist rimonabant,
      the mixed peroxisome proliferator-activated receptor agonists muraglitazar and
      tesaglitazar, the inhaled insulin preparation Exubera, and the insulin analogues
      (insulin glulisine and insulin detemir). CONCLUSION: New drugs and technologic
      advances being made available will help achieve the goals of treating patients
      with diabetes to all the appropriate metabolic targets. Many other agents that
      act on fundamental abnormalities such as energy imbalance, inflammation, and
      vascular biologic conditions are in very early stages of development but are
      likely to become available during the next 5 to 10 years.

PMID- 16627401
TI  - Determination of the spatial orientation and shape of pulmonary vein ostia by
      contrast-enhanced magnetic resonance angiography.
AB  - AIMS: For catheter ablation of atrial fibrillation (AF), proper catheter
      positioning is crucial and depends on knowledge of pulmonary vein (PV) anatomy.
      The aim of this study was to assess PV spatial orientation and ostial shape by
      contrast-enhanced magnetic resonance angiography (CE-MRA). METHODS AND RESULTS:
      In 30 consecutive AF patients, CE-MRA was performed prior to ostial ablation.
      Using a centre-line technique, the PV ostium was defined perpendicular to this
      centre-line. Minimal and maximal ostial diameters, ostial perimeter, and angles
      in the anatomical frontal and transverse planes were measured. Twenty-one
      patients had four separate PVs. In four patients, there was a distinct right
      middle PV and in five a common left common PV was found. Left-sided PV ostia were
      smaller and more elliptical than right-sided PVs. In the transverse plane, the
      ostia of both superior PVs were directed anteriorly (LS -15 +/- 13 degrees , RS 
      13 +/- 11 degrees ) and both inferior PV ostia were directed posteriorly (LI 23
      +/- 15 degrees , RI 39 +/- 15 degrees ). In the frontal plane, both superior PV
      ostia pointed upwards (LS -27 +/- 14 degrees , RS -33 +/- 12 degrees ) while the
      inferior ostia were directed horizontally (LI 2 +/- 11 degrees , RI 3 +/- 13
      degrees ). CONCLUSION: PV ostial shape and spatial orientation are variable and
      can be visualized adequately by CE-MRA.

PMID- 16627402
TI  - Simple and efficient identification of conduction gaps in post-ablation recurring
      atrial flutters.
AB  - AIMS: Cavo-tricuspid isthmus (CTI) radiofrequency (RF) ablation is a curative
      therapy for common atrial flutter (AFl), but is associated with a recurrence rate
      of 5-26%. Although complete bidirectional conduction block is usually achieved,
      the recurrence of AF is due to recovered conducting isthmus tissue through which
      activation wavefronts pass. We evaluated a simple and efficient
      electrophysiological strategy, which pinpoints the ablation target. METHODS AND
      RESULTS: Twenty-five patients (19 men), mean age 61 +/- 6, with recurrent AFl
      required a repeat ablation, 250 +/- 160 days after a successful RF CTI procedure.
      Transverse CTI conduction was monitored during AFl or coronary sinus (CS) pacing
      by a 24-pole mapping catheter positioned in the right atrium (RA), with the
      distal poles in the CS, proximal poles on the lateral RA, and intermediate poles
      on the CTI. A slow conduction area traversing the CTI (velocity, 37 +/- 22 vs. 98
      +/- 26 cm/s on either side, P < 0.05) and a lower potential amplitude than at
      both sides (0.2 +/- 0.15 vs. 0.5 +/- 0.5 mV, P < 0.05), defined by a bayonet
      shaped depolarization sequence, were considered to represent the incomplete line
      of block (InLOB). An ablation catheter was progressively dragged up to this
      InLOB, from the tricuspid annulus to the inferior vena cava, analysing the widely
      separated double potentials (DPs) until these coalesced. In nine patients (35%),
      the target conduction gap was a coalesced fractionated atrial potential within
      the InLOB (duration, 77 +/- 12 ms), and in 16 patients (65%), a narrow DP toward
      the healthy margins of this InLOB (duration, 28 +/- 15 ms). Adopting this
      strategy yields 100% successful re-ablation of recurring AFl leading to
      bidirectional block, with a mean 2.7 +/- 1.4 RF applications. CONCLUSION:
      Transverse CTI mapping precisely locates the InLOB and helps find conduction gaps
      along the CTI in re-ablation procedures for common AFl.

PMID- 16627403
TI  - Intraoperative endocardial microwave ablation for treatment of permanent atrial
      fibrillation during coronary artery bypass surgery: 1-year follow-up.
AB  - AIMS: Operative treatment of atrial fibrillation was initially performed as a
      maze operation in combination with mitral valve surgery or as a stand-alone
      procedure. The introduction of simplified ablation procedures led to the
      extension of operative atrial fibrillation treatment. METHODS AND RESULTS: In 102
      consecutive patients, endocardial microwave ablation was performed during
      coronary artery bypass surgery alone (n = 42) or in combination with valve
      surgery (n = 60). Patients were divided according to lesion line concept (the
      initial single lesion line concept connecting the pulmonary veins with the mitral
      valve annulus was replaced by a box lesion line concept including the left atrial
      appendage) and the complexity of the procedure. Patients were followed
      prospectively at 1, 3, 6, and 12 months post-operatively. Survival rate was 95.8%
      at 30 days and 88.5% after 1 year. There were no device-related complications. At
      all follow-ups, approximately 10% more of the patients with the first lesion line
      concept and coronary bypass operation alone showed stable sinus rhythm in
      contrast to the combination procedures. With the new lesion line concept,
      patients were significantly more often in sinus rhythm at 1-year follow-up (74%
      vs. 52%; P = 0.0026). CONCLUSION: Our results demonstrate that endocardial
      microwave ablation can be performed in combination with coronary artery bypass
      grafting with excellent conversion rate to sinus rhythm after 1 year without
      increasing the surgical risk for patients with permanent atrial fibrillation.

PMID- 16627404
TI  - Permanent form of junctional reciprocating tachycardia in adults: peculiar
      features and results of radiofrequency catheter ablation.
AB  - AIM: PJRT occurs predominantly in infants and children and is limited to small
      series in adults. The aim of this study was to describe the clinical
      presentation, electrophysiological characteristics, feasibility and safety of
      radiofrequency ablation, and the long-term prognosis in a large group of adult
      patients with the permanent form of junctional reciprocating tachycardia (PJRT).
      METHODS AND RESULTS: Forty-nine adult patients (22 male and 27 female; mean age
      43+/-16) with a diagnosis of PJRT confirmed at electrophysiological study were
      included. Eight patients (16%) presented with tachycardia-induced cardiomyopathy
      (TIC). Ventricular rate was 146+/-30 bpm. The arrhythmia was permanent or
      incessant in 23/49 cases (47%) and paroxysmal in 26/49 (53%). A significant
      correlation was found between symptom duration and tachycardia rate (r(2)=0.12,
      P=0.01). The accessory pathway (AP) was located in the right posteroseptal region
      in 37 cases (76%) and in atypical sites in 12 cases (24%). Patients with the
      incessant or permanent form of PJRT had longer duration of symptoms, more
      frequently TIC and a slower tachycardia rate. Radiofrequency catheter ablation
      was initially successful in 46 cases (94%) without any serious complication. Long
      term success rate was 100% (49/49 patients) in the absence of any antiarrhythmic
      drug treatment (mean follow-up 49+/-38 months). Regression of TIC was observed in
      all cases (8/8). CONCLUSION: PJRT in adults is often paroxysmal (53%), and the
      retrograde slowly conducting, decremental AP is not infrequently in a non
      posteroseptal location. Radiofrequency catheter ablation is highly effective and
      should be considered as the treatment of first choice in adult patients with
      PJRT.

PMID- 16627405
TI  - Classification and differential diagnosis of atrioventricular nodal re-entrant
      tachycardia.
AB  - Recent evidence on atrioventricular nodal re-entrant tachycardia has identified
      several types of this common arrhythmia, with potential therapeutic implications.
      This article reviews the relevant new information, discusses the differential
      diagnosis of atrioventricular nodal re-entrant tachycardia, and summarizes the
      electrophysiological criteria for classification of the various forms of the
      arrhythmia.

PMID- 16627406
TI  - Volume measurement by CARTO compared with cardiac magnetic resonance.
AB  - AIMS: The CARTO electrophysiological mapping system has demonstrated accurate
      results for end-diastolic ventricular volumes in casts and animals. However, in
      humans, a comparison with cardiac magnetic resonance (CMR), the non-invasive gold
      standard for volumetric analysis, has not yet been performed. METHODS AND
      RESULTS: A total of 34 (29 male) heart failure patients (NYHA class III/IV)
      underwent an electrophysiological mapping procedure with the CARTO system in the
      left ventricle (LV) (n = 34) and right ventricle (RV) (n = 12) and CMR for RV and
      LV end-diastolic volume (RVEDV and LVEDV) measurements another day. Mean LVEDV
      was comparable between CMR and CARTO (328 +/- 95 and 320 +/- 92 mL, respectively;
      P = NS), whereas RV volumes measured by CARTO were larger (CMR 140 +/- 48 vs.
      CARTO 176 +/- 47 mL; P < 0.01). Overall, we found a good correlation between CMR
      and CARTO measurements for both chambers; however, the Bland-Altman analysis
      showed a non-interchangeability of these methods. Measurement differences were
      independent of chamber size, but significantly affected by the number of acquired
      mapping points. CONCLUSION: Although CMR and CARTO showed a good correlation in
      the measurement of RVEDV and LVEDV in a group of heart failure patients, the
      clinical interchangeability of the two methods may be questioned.

PMID- 16627407
TI  - Occlusion of the proximal subclavian vein complicating pacemaker lead
      implantation.
AB  - A set of images in which a pacemaker lead replacement procedure was complicated
      by occlusion of the proximal subclavian vein is presented. However, this was not
      detected on venography performed before the procedure. Physicians should be aware
      of a more proximal occlusion of the subclavian vein while replacing pacemaker
      leads, even in cases with seemingly normal venography.

PMID- 16627408
TI  - Coronary and peripheral blood flow changes following biventricular pacing and
      their relation to heart failure improvement.
AB  - AIMS: To study the effect of cardiac resynchronization therapy (CRT) on coronary
      and peripheral arterial circulation and to assess whether their changes are
      related to the improvement in patients' functional capacity and prognostically
      important biochemical markers. METHODS AND RESULTS: Twenty-five patients were
      studied (New York Heart Association classes III and IV, left ventricular ejection
      fraction <35%, QRS>120 ms, mean age 66 +/- 2.1 years). Coronary blood flow (CBF),
      forearm blood flow (FBF), and their reserve were measured by transoesophageal
      echocardiography (in cm/s) and venous occlusion plethysmography (in mL/100
      mL/min) at baseline and following 3 months of CRT. N-terminal-pro-brain
      natriuretic peptide (Nt-pro-BNP) and serum adhesion molecules, sICAM-1 and sVCAM
      1 levels were also assessed. CRT induced a non-significant increase in resting
      CBF (baseline vs. CRT: 52.1 +/- 5.5 vs. 58.2 +/- 3.6, P: NS), whereas hyperaemic
      CBF was increased by CRT (baseline vs. CRT: 67.8 +/- 6.8 vs. 79.8 +/- 6.2, P <
      0.05). Significant increases were observed in resting FBF (baseline vs. CRT: 1.6
      +/- 0.2 vs. 2.6 +/- 0.2, P < 0.05) and hyperaemic FBF (baseline vs. CRT: 2.1 +/-
      0.2 vs. 3.2 +/- 0.3, P < 0.05). The per cent difference in hyperaemic FBF was
      related to the per cent change in Nt-pro-BNP (r = -0.71, P < 0.05) and the per
      cent improvement in exercise duration (r = 0.80, P < 0.05). CONCLUSION: CRT
      induces favourable changes in coronary and peripheral arterial function. Changes
      in peripheral blood flow are related to patients' improvement and may be
      prognostically significant.

PMID- 16627409
TI  - Upgrade to biventricular pacing in patients with conventional pacemakers and
      heart failure: a double-blind, randomized crossover study.
AB  - AIMS: To investigate whether patients with previously implanted conventional
      pacemakers and severe heart failure benefit from an upgrade to a biventricular
      system. METHODS AND RESULTS: Study inclusion criteria were New York Heart
      Association (NYHA) classes III and IV, dominant paced rhythm, and no left bundle
      branch block in the pre-pacing ECG. Ten patients with pacemakers (four VVIR due
      to slow atrial fibrillation and six DDDR, of which four were due to high-degree
      atrioventricular block and two to sinus node disease) were upgraded to a
      biventricular pacing (BVP) system. The median duration of pacing before the
      upgrade was 5.7 years. Assessments of 6-min walk test, symptom score, brain
      natriuretic peptide (pro-BNP), and echocardiography were made pre-operatively.
      After a run-in period of 1 month in BVP following the upgrade, the patients were
      randomized to a 2-month period in either BVP or right ventricular pacing (RVP),
      followed by 2 months in the other mode, in a double-blind crossover fashion.
      After each period, the pre-operative measurements were repeated. After study
      completion, patients were asked to select their preferred period. The median 6
      min walking distance was significantly longer in BVP (400 m) vs. RVP (315 m), P =
      0.02. The symptom score was also significantly better in BVP (P = 0.005). Median
      pro-BNP was significantly lower in BVP than in RVP, 3,030 vs. 5,064 ng/L (P =
      0.005). Six patients demanded an early crossover in RVP but none in BVP (P =
      0.015), and all patients except one expressed a preference for BVP. However, echo
      parameters did not show any significant differences between BVP and RVP.
      CONCLUSION: Pacemaker patients with heart failure and dominant paced heart rhythm
      benefit substantially from an upgrade to BVP, in terms of physical performance
      and symptoms. The upgrade resulted in significantly improved cardiac function as
      reflected by reduced levels of pro-BNP.

PMID- 16627410
TI  - Use of a modified introducer sheath with a side-hole to improve access to left
      ventricular veins with proximal origin.
AB  - AIMS: Despite technical advances in tools used to facilitate implantation of
      cardiac resynchronization therapy (CRT) devices, there are many hurdles related
      mainly to the variation in the anatomy of the coronary veins. One such difficulty
      is the presence of a very proximal origin of the lateral or postero-lateral
      cardiac vein. METHODS AND RESULTS: We describe an alteration of existing left
      ventricular (LV) lead delivery sheath with the creation of a side-hole 35-50 mm
      from its tip. This modification is made to provide access to proximal cardiac
      vein ostia, while maintaining adequate support for the delivery system. The
      modified introducer sheath was used in the implantation of six CRT systems (four
      defibrillators and two pacemakers) in patients who had a proximal origin of the
      lateral or postero-lateral cardiac vein, all of which were successful and without
      complications. CONCLUSION: In those patients with unusual proximal origin of
      target LV veins, modifications of the introducer sheath with the creation of a
      side-hole facilitate the successful implantation of the LV pacing lead. Until
      this modified sheath is tested, this technique is considered experimental and may
      carry unknown risks.

PMID- 16627411
TI  - FOLLOWPACE study: a prospective study on the cost-effectiveness of routine follow
      up visits in patients with a pacemaker.
AB  - AIMS: This communication describes the design of the FOLLOWPACE study. The
      overall aim of FOLLOWPACE is to quantify the cost-effectiveness of routine follow
      up visits in patients with a pacemaker (PM). Specific aims are (i) to quantify
      the incidence of complications and the quality of life 1 year after PM
      implantation; (ii) to quantify which baseline characteristics measured during
      implantation are predictors of the occurrence of complications and quality of
      life after 1 year; (iii) to determine the added predictive value of follow-up
      measurements to improve the efficiency of follow-up and to demonstrate which
      follow-up measurements are redundant. METHODS AND RESULTS: FOLLOWPACE is a
      prospective, observational, prognostic cohort study. About 40 PM centres in the
      Netherlands will participate to include about 2,500 patients. Each patient aged
      >or=18 receiving a PM for the first time is eligible. At baseline, i.e. time of
      implantation, all potential predictors of complications and quality of life after
      1 year are documented. After implantation, follow-up visits will be carried out
      conforming with routine care, usually three in the first year. At these visits,
      other potential prognostic predictors will be documented. Primary outcome is the
      incidence of PM- or cardiac complications at 1 year. Secondary outcome parameters
      are quality of life and costs after 1 year. CONCLUSION: This study will lead to
      definition of a more efficient routine follow-up schedule for patients with a PM,
      aiming to reduce time and energy while preserving the safety of pacing therapy
      and the prognosis of the patient. The study will ultimately provide evidence
      based guidelines for PM follow-up including knowledge of the responsibilities of
      cardiologists, technicians, and representatives of PM manufacturers.

PMID- 16627412
TI  - Acute performance evaluation of a new ventricular automatic capture algorithm.
AB  - AIMS: This study evaluated the acute clinical performance of a new ventricular
      automatic capture algorithm developed to work with all lead types and pacing
      vectors. METHODS AND RESULTS: During regular pacemaker implant or replacement,
      AutoThreshold and manual threshold tests were performed in ventricular unipolar
      (UP) and bipolar (BP, if applicable) pacing using a customized external prototype
      INSIGNIA pacemaker. The success rate and accuracy of two different modes
      (commanded and ambulatory) of the automatic capture algorithm were used to
      evaluate the performance. Loss-of-capture events (two consecutive non-captured
      beats without backup pacing) were used to assess safety. Data of 53 patients (33
      DDD/20 VVI) from four medical centres were analysed. Tested leads included 43 BP
      and 10 UP from nine manufacturers, and seven had electrodes with low
      polarization. The rate of successful commanded and ambulatory AutoThreshold tests
      was 96 and 94%, respectively, with an average absolute threshold difference
      compared with manual threshold of < 0.1 V at 0.4 ms (commanded 0.07 +/- 0.07 V
      and ambulatory 0.08 +/- 0.07 V). There was no significant difference in
      performance between UP/BP pacing, polarization, and lead type. No loss-of-capture
      event was observed. CONCLUSION: When successful, the ventricular automatic
      capture algorithm accurately determined pacing thresholds in either a UP or BP
      pacing configuration among all leads tested.

PMID- 16627413
TI  - Predictors of chronotropic incompetence in the pacemaker patient population.
AB  - AIMS: We prospectively evaluated results from cardiopulmonary exercise testing
      for chronotropic incompetence (CI) in a cohort of 292 pacemaker patients. In
      addition, we evaluated comorbidity and antiarrhythmic patient data as indicators
      of CI. METHODS AND RESULTS: On the basis of exercise stress testing and
      application of the definition of CI by Wilkoff, 51% of our cohort was categorized
      as having CI. Indications for pacemaker implant for this patient group were 42%
      atrioventricular block, 56% sinus node disease, and 59% atrial fibrillation.
      Maximum oxygen uptake (VO(2) max) and exercise duration were significantly
      reduced among CI pacemaker patients, whereas oxygen uptake at the anaerobic
      threshold remained unchanged. The following clinical characteristics were
      significant predictors of CI: existence of coronary artery disease (P = 0.038),
      presence of an acquired valvular heart disease (P = 0.037), and former cardiac
      surgery (P = 0.041). Age, gender, arterial hypertension, cardiomyopathy,
      congenital heart disease, left ventricular ejection fraction, and time period
      between stress-exercise examination and pacemaker implantation were not
      significant predictors of CI. Chronic antiarrhythmic therapy with digitalis (P =
      0.013), beta blockers (P = 0.036), and amiodarone (P = 0.045) were significant
      predictors of CI. In contrast, medication with class I and IV antiarrhythmics had
      no significant correlation with CI. CONCLUSION: We found the following
      characteristics predictive of CI in this pacemaker patient population: VO(2) max,
      existence of coronary artery disease or acquired valvular heart disease, previous
      cardiac surgery, as well as medication with digitalis, beta blockers, and
      amiodarone.

PMID- 16627414
TI  - Biventricular vs. left univentricular pacing in heart failure: rationale, design,
      and endpoints of the B-LEFT HF study.
AB  - AIMS: Cardiac resynchronization therapy (CRT) confers sustained therapeutic
      benefits to patients suffering from congestive heart failure (CHF) due to
      systolic dysfunction associated with ventricular dyssynchrony. Biventricular
      (BiV) pacing has, thus far, been the preferred method, as it corrects both
      electrical and mechanical dyssynchrony. Left ventricular (LV) only pacing, which
      has conferred similar benefits in pilot studies, may be an alternative treatment
      method. 'Biventricular vs. left univentricular pacing with ICD back-up in heart
      failure patients' (B-LEFT HF) is an international, prospective, randomized,
      parallel-design, double-blind, clinical trial to examine whether LV only pacing
      is as safe and effective as BiV pacing in patients suffering from CHF. METHODS
      AND RESULTS: The trial will randomly assign 172 patients to either LV only or BiV
      pacing. The study has prospectively defined efficacy endpoints to be evaluated at
      6 months, which are (i) changes in functional capacity and degree of reverse
      remodelling (primary) and (ii) changes in the heart failure clinical composite
      response (secondary). CONCLUSION: Because LV only pacing in CRT is likely to be
      technically less challenging and costly than BiV, a specifically designed study
      is needed to compare the safety and effectiveness of the two configurations. B
      LEFT HF has been designed to settle this critical issue.

PMID- 16627415
TI  - Four years experience of a nurse-led elective cardioversion service within a
      district general hospital setting.
AB  - AIMS: External direct current cardioversion is an effective method of restoring
      sinus rhythm (SR) in patients with persistent atrial arrhythmias. Increasing
      demand for hospital beds, together with a reduction in junior doctors' hours, has
      adversely affected cardioversion provision. A regular nurse-led cardioversion
      service conducted in a dedicated hospital day-unit was introduced to resolve
      these constraints. There are limited data on the safety or efficacy of such a
      service. METHODS AND RESULTS: All cardioversions between October 2000 and October
      2004 were performed by an appropriately trained specialist nurse, under general
      anaesthesia. Patients attended a pre-assessment clinic. Energy requirements for
      initial and subsequent defibrillations were guided by a local protocol in
      accordance with the guidelines from American Heart Association, American College
      of Cardiology, and the European Society of Cardiology. Rectilinear biphasic
      defibrillation was introduced in January 2004 with an appropriate protocol
      amendment. In the absence of complications, the aim was to discharge patients the
      same day. A total of 578 cardioversions (475 monophasic; 103 biphasic) were
      performed on 464 patients [72.1% male, mean (+/- SD) age 67.8 +/- 9.4 years] with
      atrial fibrillation (AF) (89.7%) and atrial flutter (10.3%). SR was restored in
      84.0 and 100% of patients with AF and atrial flutter, respectively, which
      increased to 90.2 and 100% following the introduction of biphasic defibrillation.
      Biphasic shocks cardioverted AF with less energy (163 +/- 22 vs. 289 +/- 81 J)
      and less cumulative energy (230 +/- 139 vs. 455+/-255 J) than monophasic (P <
      0.001 for both), despite no difference in the duration of AF (P = 0.26) or
      patient age (P = 0.78). Two patients required hospital admission due to transient
      bradycardia; both were discharged within 72 h, without the need for permanent
      pacing. A total of 99.6% of patients was discharged home the same day; there were
      no deaths. CONCLUSION: The provision of a nurse-led elective cardioversion
      service is feasible and effective, without compromising safety.

PMID- 16627416
TI  - The role of pacing mode in the development of atrial fibrillation.
AB  - Asynchronous ventricular pacing has been shown to increase the risk of
      development of atrial fibrillation (AF) because of various mechanisms: retrograde
      atrioventricular (AV) conduction with increase in atrial pressure causing acute
      atrial stretch and reverse flow in the pulmonary veins, mitral regurgitation,
      reduced coronary blood flow, adverse neuroendocrine reactions, etc. Dual-chamber
      pacing preserves atrioventricular synchrony. However, in randomized multicentre
      trials comparing VVI(R) with DDD(R) pacing, AF is only slightly less frequent in
      the dual-chamber mode. This is most likely due to unnecessary ventricular pacing,
      which is frequent in dual-chamber pacing. At nominal values, dual-chamber devices
      usually do not permit intrinsic AV conduction but promote delivery of the
      ventricular stimulus at an inappropriate time in an inappropriate place.
      Programming of long AV delays facilitates spontaneous AV conduction but usually
      cannot completely avoid unnecessary ventricular pacing and causes other problems
      in the dual-chamber mode. Atrial septal lead placement can improve left-sided AV
      synchrony and promote spontaneous AV conduction. Programming of the AAI(R) mode
      is superior to the dual-chamber mode but cannot be used if AV conduction is
      impaired intermittently or permanently. Therefore, dedicated algorithms enhancing
      spontaneous AV conduction in the dual-chamber mode are desirable for a large
      proportion of pacemaker patients.

PMID- 16627417
TI  - Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular
      pacing.
AB  - AIMS: To examine the performance of AAIsafeR2, a new pacing mode to minimize the
      cumulative proportion of ventricular pacing in patients who do not need regular
      ventricular support. METHODS AND RESULTS: The safety of AAIsafeR2 was examined in
      123 recipients (73 +/- 12 years old, 51% men) of dual chamber pacemakers
      implanted for sinus node dysfunction, paroxysmal AV block or the bradycardia
      tachycardia syndrome. Data were collected from pacemaker diagnostics, and the
      first 43 patients underwent 24-h Holter recordings before being discharged from
      the hospital with AAIsafeR2 activated. No adverse event related to AAIsafeR2 was
      observed. All ventricular pauses detected on Holter tapes triggered immediate
      back-up ventricular pacing. Appropriate switches to DDD occurred in 97 of 123
      patients. In 69 of 123 devices (56%) switches to DDD were non-sustained, and the
      average % ventricular pacing in this group was 0.2+/-0.5%. CONCLUSION: AAIsafeR2
      mode seems to be safe and reliable in patients with infrequent slowing or pauses
      in ventricular activity, while maintaining ventricular pacing below 1%.

PMID- 16627418
TI  - Abnormalities of pulmonary venous flow in patients with lone atrial fibrillation.
AB  - AIMS: Mechanisms underlying lone atrial fibrillation (LAF) are poorly defined. We
      sought to investigate indices of left atrial (LA) function in patients with
      recurrent LAF, in comparison with that in healthy subjects. METHODS AND RESULTS:
      Investigations were performed in 42 patients aged 51.8 +/- 8.7 at least 30 days
      after the last episode of LAF and in 38 healthy controls. Each subject underwent
      echocardiographic evaluation including left ventricular parameters and LA
      function indices. LA ejection fraction served as a measure of LA systolic
      performance, and acceleration (SAT) and deceleration time (SDT) of systolic phase
      of pulmonary venous flow (PVF) corresponded to LA relaxation and compliance,
      respectively. Patients with LAF showed significantly lower values of SAT (179.1
      +/- 63.2 vs. 199.2 +/- 45.1 ms, P < 0.02) and higher values of SDT (250.8 +/-
      81.6 vs. 211.7 +/- 57.3 ms, P < 0.01) when compared with controls. No significant
      differences were found with respect to other measured parameters. The combination
      of SAT < 185 ms and SDT > 239 ms showed a positive predictive value of 92% in the
      identification of patients prone to LAF. CONCLUSION: This study suggests that (i)
      patients with LAF have abnormalities of the systolic phase of PVF and (ii)
      Doppler estimation of PVF seems to be very valuable in the evaluation of patients
      with LAF.

PMID- 16627419
TI  - Right atrial overdrive pacing for prevention of symptomatic refractory atrial
      fibrillation.
AB  - AIMS: Our aim was to investigate whether right atrial overdrive pacing is
      effective for the prevention of atrial fibrillation (AF) in patients without
      bradyarrhythmias. METHODS AND RESULTS: Patients with symptomatic paroxysmal or
      persistent AF refractory to at least two Class I or III antiarrhythmic drugs and
      without bradyarrhythmias were included. Successful therapy was defined as the
      combination of (a) a reduction of AF burden with or without AAD use >75%, (b)
      total AF burden < or =5% per year, and (c) less than one electrical cardioversion
      per year. Lower rate was set at 70 b.p.m. Additional AF prevention and
      termination features were used in case of no success. After a median follow-up of
      18 (10-55) months, therapy was effective in 19 of the 36 included patients (53%).
      In 74% of the successfully treated patients, additional antiarrhythmic drugs were
      used. In successfully treated patients, the AF burden was reduced from 15% (5
      100%) to 0% (0-4%). Multivariate analysis showed that the concomitant use of a
      Class I or III antiarrhythmic drug, a lower AF burden before implantation and the
      use of an angiotensin converting enzyme inhibitor were predictors of successful
      therapy. CONCLUSION: Right atrial overdrive pacing in combination with
      antiarrhythmic drugs seems an attractive treatment option in drug refractory
      symptomatic AF patients.

PMID- 16627420
TI  - Passive electrode effect reduces defibrillation threshold in bi-filament middle
      cardiac vein defibrillation.
AB  - AIMS: To investigate whether a passive electrode effect decreases defibrillation
      threshold (DFT) in multi-filament middle cardiac vein (MCV) defibrillation.
      METHODS AND RESULTS: Twelve pigs underwent active housing (AH) insertion, with
      defibrillation coils placed transvenously in right ventricular apex and superior
      vena cava. The MCV was cannulated, and 1.12F, 50 mm coil electrodes (Ela Medical
      SA, France) were deployed in its right and left branches. Lead placement was
      possible in 11 of 12 animals. DFT (J, mean +/- SD) was determined by three
      reversal binary search and compared between the MCV monofilament (single filament
      deployed) and the AH (25.9 +/- 10.9) and the MCV mono + passive filaments (both
      filaments deployed, one connected) and the AH (19.9 +/- 11.4); 24% DFT reduction
      P = 0.008. CONCLUSION: A bystander electrode adjacent to a monofilament electrode
      in the MCV reduces DFT by 24% when compared with monofilament MCV alone.
      Microfilament electrodes decrease DFT as auxiliary anode but not as sole anode.

PMID- 16627421
TI  - Clinical surveillance of a tined, bipolar, silicone-insulated ventricular pacing
      lead.
AB  - AIMS: This study assesses short- and long-term performance of the S80TB
      ventricular lead manufactured by Sorin Biomedica, Italy. METHODS AND RESULTS:
      Three hundred and thirty leads were implanted and had complete follow-up with us
      for a minimum of 60 months or up to failure, removal, and/or patient death (mean
      40 months, range: 1 day to 81 months). Thirty-two patients (9.6%) had spontaneous
      lead-related complications: 7 (2.1%) occurred during the first week; 25 (7.6%)
      had chronic complications, of which 20 (6.1%) necessitated re-operations; 3
      (0.9%) were lead material failures. Of the 110 re-operations (90 pacemaker
      replacements and 20 operations due to complications), 7 additional cases (6.4%)
      were complicated by unique connector damage that occurred during disconnection of
      the lead from the connector block. The Kaplan-Meier estimated 5-year lead
      survival free of lead material failure and free of any significant lead
      complication were 97.9 and 87%, respectively. CONCLUSION: The S80TB lead
      demonstrates an acceptable rate of acute and chronic spontaneous complications
      and very few lead material failures over 5 years of follow-up. However, there
      seems to be a relatively high incidence of connector damage during disconnection
      from the connector block. Extra caution is required during those procedures in
      patients with this lead.

PMID- 16627422
TI  - Cost of diagnosis and treatment of syncope in patients admitted to a cardiology
      unit.
AB  - AIMS: Despite the large number of hospital admissions due to syncope, information
      on the in-hospital cost of management of these patients remains incomplete.
      METHODS AND RESULTS: In order to assess such cost, we analysed the clinical
      histories of the patients suffering from syncope who were admitted to our Unit of
      Cardiology in 2003. We determined the length of stay (in days) for each
      inpatient, the number of diagnostic tests performed, and the various therapeutic
      procedures undertaken. Two hundred and three patients (mean age 68 +/- 14, 49%
      female) were admitted because of syncope. Final diagnoses on discharge were drug
      induced syncope in 10 patients, vasovagal syncope in 11, syncope secondary to
      cardiac ischaemia in 18, valvular disease in 4, rapid supraventricular arrhythmia
      in 20, ventricular arrhythmia in 19, atrioventricular block in 90, and
      unexplained syncope in 31 patients. Of these 203 patients, 70 (34.5%) had a
      previous history of cardiac disease. The global cost for all 203 patients was
      2,264,979 Euros. The overall cost per patient was 11,158 Euros (range: 1651
      31,762) including stay, diagnosis, and treatment. The overall cost of hospital
      stay per patient was 3718 Euros (range: 1436-5679). The overall cost per
      diagnosis of the 203 patients was 1141 Euros (range: 155-3577), and the cost of
      the therapeutic procedures required was 6299 Euros (range: 0-23 115). The most
      expensive were those cases of syncope secondary to ventricular arrhythmia, the
      cost of which is 20 times that of drug-induced syncope. CONCLUSION: The cost per
      diagnosis and treatment of a patient admitted because of syncope varies widely
      with important differences depending on the specific cause.

PMID- 16627423
TI  - Accelerated sinus rhythm with high grade A-V block during head-up tilt testing.

PMID- 16627424
TI  - Long-term safety and efficacy of slow pathway ablation in patients with
      atrioventricular nodal re-entrant tachycardia and pre-existing prolonged PR
      interval.
AB  - The association of atrioventricular nodal re-entrant tachycardia (AVNRT) and pre
      existing prolonged PR interval is unusual. Radiofrequency (RF) ablation in such
      patients may be associated with an increased risk of immediate and delayed AV
      block. The aim of our study is to assess the long-term efficacy and safety of
      slow pathway ablation in this population. We studied 10 patients (4 males and 6
      females) with pre-existing prolonged PR interval of 68 consecutive patients with
      AVNRT. All had slow-fast subtype of AVNRT. The mean PR interval was 222 +/- 15 ms
      before RF. The patients with pre-existing prolonged PR were older (69 +/- 15 vs.
      54 +/- 17, P = 0.008) and their tachycardias were slower (387 +/- 102 vs. 323 +/-
      73 ms; P < 0.05). Transient complete AV block (<5 s) occurred in two patients.
      None had permanent complete AV block. One patient had a significant increase in
      PR interval (from 220 to 320 ms). The mean post-RF PR interval was 232+/-37 ms (P
      = n.s.). Over a mean follow-up of 39 +/- 21 months, none had a recurrence of
      tachycardia nor developed higher degree AV block. In conclusion, in patients with
      AVNRT and pre-existing prolonged PR interval, a slow pathway ablation appeared
      efficient and safe. From our data, no delayed AV block developed on a long follow
      up. Most of the patients with periprocedural transient AV block had no evidence
      of dual AV node physiology, suggesting that, in this population, absence of dual
      AV node physiology may be associated with a higher risk of AV block during slow
      pathway ablation.

PMID- 16627425
TI  - Atrioventricular nodal re-entrant tachycardia with QRS voltage and cycle length
      alternation and aberrant conduction due to two distinct antegrade slow pathways.
AB  - QRS voltage and cycle length alternation can be seen during supraventricular re
      entrant tachycardias, especially in atrioventricular (AV) re-entrant tachycardia.
      We present a case of a 20-year-old man, in which AV nodal re-entrant tachycardia
      (AVNRT) shows alternation of QRS voltage and cycle length, as well as right
      bundle branch block aberration due to a re-entrant circuit using two distinct,
      beat-to-beat alternating slow AV nodal pathways antegradely and a single fast
      pathway retrogradely. Although more than one antegrade slow pathway exists,
      creation of a single lesion at the right posterior atrial septum using the
      conventional right-sided approach successfully eliminated AVNRT.

PMID- 16627426
TI  - Mapping and ablation of atypical flutter in congenital heart disease with a novel
      three-dimensional mapping system (Carto Merge).
AB  - Mapping and successful ablation of an intra-atrial re-entry tachycardia in a
      patient after Fontan operation were performed within the anatomy, superimposed
      from the computed tomography study. In this case, the new system enabled us to
      display the complex anatomy of the right atrium in detail, whereas the
      conventional electro-anatomic three-dimensional geometry showed significant
      inconsistencies.

PMID- 16627427
TI  - Spontaneous automaticity of an atriofascicular accessory pathway.
AB  - In a 12-year-old girl with history of recurrent palpitation, an ambulatory 24 h
      Holter electrocardiogram showed a wide QRS complex rhythm with atrioventricular
      dissociation. During an electrophysiology study, an atriofascicular pathway was
      diagnosed with an inducible antidromic atrioventricular re-entrant tachycardia.
      At slower heart rates, the patient had a wide QRS complex escape rhythm similar
      to the tachycardia and the pre-excited QRS complex morphology. This indicates the
      presence of pacemaker-like cells in the atriofascicular accessory pathway giving
      rise to the wide QRS complex escape rhythm at a slower heart rate.

PMID- 16627428
TI  - Cardiac resynchronization via the femoral vein: a novel method in cases with
      contraindications to the pectoral approach.
AB  - We describe a case involving biventricular pacemaker implantation via the right
      femoral vein in a patient where subclavian vein access was not possible.

PMID- 16627429
TI  - Permanent pacing using a coronary sinus lead in a patient with univentricular
      physiology: an extended application of biventricular pacing technology.
AB  - In the past, patients requiring permanent pacing with difficult right ventricular
      (RV) access were usually subjected to epicardial pacing by a surgical approach.
      This report describes a young patient with univentricular physiology following
      repeated palliative surgery for complex congenital heart disease. The patient had
      symptomatic complete heart block and a dual chamber pacemaker with transvenous
      atrial and ventricular leads was implanted successfully. The ventricle was paced
      through the posterolateral cardiac vein with a lead specially designed for
      cardiac resynchronization therapy. This case illustrates an extended application
      of the recently developed coronary sinus lead in selected patients, when
      conventional RV endocardial pacing is impossible.

PMID- 16627430
TI  - Impact of intraventricular conduction delay on coronary haemodynamics: a study
      with intracoronary Doppler in patients with bundle branch blocks and normal
      coronary arteries.
AB  - AIMS: The impact of right bundle branch block (RBBB) and left bundle branch block
      (LBBB) on myocardial perfusion is not completely understood as data are often
      blurred by underlying cardiac disease. The present study investigates whether
      conduction delays per se affect coronary perfusion-an indirect measure of
      myocardial oxygen demand. METHODS AND RESULTS: Intracoronary Doppler and
      ultrasound were performed in 8 patients with RBBB, 10 patients with LBBB, and 10
      control subjects. All patients had angiographically normal coronary arteries and
      normal left ventricular function. Baseline (bAPV) and adenosine-induced
      hyperaemic average flow velocity and coronary flow velocity reserve (CFVR) were
      measured in left anterior descending arteries. Intravascular ultrasound showed no
      difference in lumen cross-sectional area and plaque burden between groups.
      Patients with RBBB and LBBB had higher bAPV values than controls (19.0 +/- 4.9,
      21.9 +/- 5.1, and 14.6 +/- 2.4 cm/s, respectively; ANOVA P = 0.003). There was no
      difference between patients with LBBB and RBBB compared with controls in CFVR
      (2.8 +/- 0.5, 3.0 +/- 1.0, and 3.4 +/- 0.7, respectively; ANOVA P = 0.21).
      CONCLUSION: Bundle branch blocks, in particular LBBB, are associated with an
      increased coronary flow velocity, which indicates enhanced myocardial oxygen
      demand on the basis of mechanoenergetic disturbance. This may contribute to the
      unfavourable outcome of patients with intraventricular conduction delay.

PMID- 16627431
TI  - Cardiac uptake of progenitor cells in patients with moderate-to-severe left
      ventricular failure scheduled for cardiac resynchronization therapy.
AB  - AIMS: Injury to the heart causes haematopoietic and endothelial progenitor cells
      (PCs) to migrate to the site of damage and to undergo PC differentiation, which
      may contribute to angiogenesis and myocardial tissue repair. We sought to
      determine the cardiac uptake of PC in patients with moderate-to-severe congestive
      heart failure (CHF) scheduled for cardiac resynchronization therapy. METHODS AND
      RESULTS: A total of 28 patients was included in the study. Fourteen patients had
      moderate-to-severe CHF with a mean left ventricular ejection fraction (LVEF) of
      20 +/- 9%. The remaining patients had a normal LVEF and served as controls. PCs
      (CD34(+) and CD34(+)/CD117(+)) were quantified using a fluorescence-activated
      cell sorter. In CHF patients, PCs were determined from whole blood samples taken
      from the aorta, the coronary sinus (CS), and the superior vena cava (SVC) during
      right and left heart catheterization. Cardiac PC uptake was determined as the
      difference in PC levels between the aorta and the CS. Differences in CD34(+)PC
      counts (Delta0.11 +/- 0.98 x 10(3) mL(-1)) and relative amount of
      CD34(+)/CD117(+)PC (Delta0.08 +/- 0.31%) between the aorta and the CS were not
      significant. PC levels were comparable between the SVC, CS, and aorta. CD34(+)
      and PC levels did not correlate with New York Heart Association class (r(2) =
      0.22), LVEF (r(2) = 0.01), LV diameter (r(2) = 0.05), QRS complex duration (r(2)
      = 0.1), or maximal O(2) uptake during exercise (r(2) = 0.08). There was no
      difference between patients with ischaemic cardiomyopathy (ICM) and non-ICM.
      Systemic PC levels were not different compared with age-matched controls without
      LV failure (CD34(+): 4.61 +/- 1.83 x 10(3) mL(-1) vs. control: 5.25 +/- 1.67 x
      10(3) mL(-1); P = n.s.). CONCLUSION: Moderate-to-severe chronic CHF is not
      associated with elevated PC levels in the systemic circulation. A measurable
      cardiac uptake of CD34(+) and CD34(+)/CD117(+)PC cannot be demonstrated by FACS
      analysis in this cohort of patients.

PMID- 16627432
TI  - First multi-centre evaluation of a knowledge-based implant-assistant for
      implantable cardioverter-defibrillators.
AB  - AIMS: Modern implantable cardioverter-defibrillators (ICDs) place increasing
      demands on the physician, as their complexity requires more and more knowledge
      and effort in handling them. To overcome this problem an implant-assistant has
      been developed, which transfers clinical data entered by the physician into a
      complete set of parameters for programming a dual-chamber ICD (Tachos-DR,
      Biotronik, Berlin, Germany) at DFT testing (DFT-Prog) and first permanent
      programming (Perm-Prog) after implant. METHODS AND RESULTS: Routine ICD
      implantations were initially evaluated by clinical experts at 19 centres in USA
      and Europe from 178 patient files. The rating of parameters was related to the
      number of parameters available in each patient. For DFT-Prog, 98.4% of parameter
      suggestions were identical to experts' expectations, an additional 1.0% were
      accepted, 0.5% were rejected, and none was considered harmful. This resulted in
      an overall acceptance of 94.4% of the DFT-Prog. For Perm-Prog, 96.1% of
      parameters were identical to those advised by experts, an additional 2.4% were
      accepted, 1.5% rejected, and seven parameters (0.04%) were considered potentially
      harmful by experts with an overall acceptance of 86.5%. Adaptation of the implant
      assistant increased the overall acceptance to 100% for DFT-Prog and 90.6% for
      first Perm-Prog without any potentially harmful suggestions. CONCLUSION: The ICD
      implant-assistant, which allows the physician to programme ICDs directly from
      clinical data, is a promising method to simplify the programming of modern ICDs.

PMID- 16627433
TI  - Health-related quality of life of patients with implantable cardioverter
      defibrillators compared with that of pacemaker recipients.
AB  - AIMS: Studies indicate a poorer quality of life (QoL) for implantable
      cardioverter defibrillator (ICD) patients than for the general population.
      However, studies comparing the QoL of ICD patients with that of patients with
      other implantable cardiac devices are scarce. We hypothesized that ICD patients
      had a poorer QoL than pacemaker patients. METHODS AND RESULTS: All ICD patients
      living in Iceland at the beginning of 2002 (44 subjects), and a comparison group
      of 81 randomly selected patients with pacemakers were invited to participate. The
      Icelandic Quality of Life Questionnaire (IQL), the General Health Questionnaire
      (GHQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI)
      were submitted to measure QoL, psychiatric distress, and symptoms of anxiety and
      depression. The ICD and pacemaker groups did not differ on IQL, BAI, BDI, or GHQ
      scores. ICD patients were as a group more fearful of death (P = 0.056) and showed
      more concerns about returning to work (P = 0.072), although these items fell just
      short of statistical significance. CONCLUSION: Contrary to our expectations, ICD
      patients had a comparable QoL with pacemaker recipients and were not more likely
      to suffer from anxiety, depression, or general psychiatric distress. These
      findings are encouraging in view of expanding ICD indications.

PMID- 16627434
TI  - Detection of refrigerator-associated 60 Hz alternating current as ventricular
      fibrillation by an implantable defibrillator.
AB  - This report describes a patient with an implantable defibrillator who suffered an
      inappropriate defibrillation shock upon retrieving some food items from his
      inadequately earthed refrigerator. Noise typical of electrical interference can
      be observed in the stored electrogram of the episode. The patient was instructed
      to earth his home appliances, but he decided to avoid his refrigerator
      altogether, and has had no subsequent shocks.

PMID- 16627435
TI  - Transient ST-segment-elevation during pulmonary vein ablation using
      circumferential coiled microelectrodes in a prospective multi-centre study.
AB  - AIMS: Paroxysmal atrial fibrillation (PAF) is predominantly triggered by focal
      ectopies located within the pulmonary veins (PV). The BITMAP Study (Breakthrough
      and Isolation Trial: Mapping and Ablation of Pulmonary Veins) investigated
      prospectively the safety and efficacy of a catheter design with circumferential
      mapping and ablation electrodes. We report the phenomenon of ST-segment-elevation
      during catheter placement in the left atrium (LA) and superior PVs in this multi
      centre study. METHODS AND RESULTS: Forty-three patients (57+/-10 years) with PAF
      were included in this study. Radiofrequency catheter (RFC) ablation supported by
      the 4F REVELATION Helix microcatheter (Cardima Inc., Freemont, CA, USA) with
      eight distal-coiled microelectrodes for bipolar mapping and ablation. RFC was
      applied at the ostial region of PV (30 W, 45-50 degrees C) with a maximum of four
      RFC applications per electrode. In four of the 43 patients from three centres, we
      recorded the occurrence of ST-segment-elevation greater than 0.2 mV and
      accompanying left thoracic discomfort. The ECG changes and the symptoms started
      abruptly and lasted for 4.2+/-2.2 min. Pericardial effusion could instantaneously
      be excluded by echocardiography in all cases. Coronary angiograms were performed
      in three patients with the longest episodes; no thrombotic material or air emboli
      were present. The symptoms and the ECG changes resolved completely in all
      patients. CONCLUSION: The phenomenon of ST-segment-elevation during LA- and PV
      mapping in patients with PAF may be a common occurrence. In this prospective
      multi-centre trial, we demonstrated the reversibility of this phenomenon; no
      cardiovascular or cerebral damage was reported during both the procedure and the
      follow-up. Although the mechanism is still unclear, vasospasm may contribute to
      this phenomenon because of autonomic dysregulation.

PMID- 16627436
TI  - Incidence, location, and cause of recovery of electrical connections between the
      pulmonary veins and the left atrium after pulmonary vein isolation.
AB  - AIMS: The aim of this study was to reveal the incidence, location, and cause of
      recovery of the electrical connections (ECs) between the left atrium and the
      pulmonary veins (PVs) after the segmental ostial PV isolation (PVI). METHODS AND
      RESULTS: Pulmonary vein mapping and successful PVI were performed using a
      computerized three-dimensional mapping system (QMS2trade mark) with a basket
      catheter in 167 PVs in 53 consecutive patients with atrial fibrillation (AF). In
      14 patients with recurrent AF after PVI, the same PV mapping and isolation as in
      the first procedure were performed, and the PV potential maps constructed by QMS2
      in two different procedures were compared. Forty-nine recovered ECs were observed
      in 27 PVs, and all were eliminated by a few local radiofrequency (RF)
      applications. Thirty-four (69%) of those ECs recovered at the edge of original
      ECs, and another 15 (31%) recovered at the mid-portion of the continuous broad
      original ECs. CONCLUSION: Electrical connection recovery occurred most commonly
      at the edges of original ECs and occasionally at the mid-portion of continuous
      broad original ECs after PVI probably due to tissue oedema neighbouring the
      segmental RF lesions. Further RF lesions at the edge of original ECs and linear
      ablation to the continuous broad ECs may help reduce AF recurrence.

PMID- 16627437
TI  - Atrio-oesophageal fistula following circumferential pulmonary vein ablation:
      verification of diagnosis with multislice computed tomography.

PMID- 16627438
TI  - Development of thrombus on a transseptal sheath in the left atrium during
      attempted electrical pulmonary vein isolation for the treatment of paroxysmal
      atrial fibrillation.

PMID- 16627439
TI  - Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective,
      randomized, placebo-controlled study.
AB  - AIMS: To compare the therapeutic efficacy of placebo, propranolol, and fluoxetine
      in patients with vasovagal syncope (VVS). METHODS AND RESULTS: Ninety-six
      consecutive patients with VVS were randomized to treatment with placebo,
      propranolol, or fluoxetine and followed-up for 6 months. Before and during
      treatment, they reported their syncopal and presyncopal episodes and graded their
      well-being, expressed as the general evaluation of life, general activities, and
      everyday activities (each scaled from 1 = very good to 5 = very bad). Two
      patients refused follow-up. Among the remaining 94, no difference between groups
      was observed regarding the distribution of time of vasovagal events (syncopes or
      presyncopes) during follow-up (log-rank test). No difference was also observed
      when syncopes and presyncopes were assessed separately. Eighteen patients
      discontinued therapy. Among the remaining 76 ('on-treatment' analysis), the mean
      time to a vasovagal episode (syncope or presyncope) was significantly longer in
      the fluoxetine group when compared with the two other groups (log-rank test, P <
      0.05). A significant difference in favour of fluoxetine was also observed
      regarding presyncopes. The difference between groups regarding the syncope-free
      period was not significant. During therapy, patients' well-being was improved
      (decreased) only in the fluoxetine-group (13.4 +/- 0.7 vs. 15.4 +/- 0.9 before
      treatment, P < 0.01). CONCLUSION: Fluoxetine seems to be equivalent to
      propranolol and placebo in the treatment of VVS. However, it improves patients'
      well-being and might be more effective in reducing presyncopes and total
      vasovagal events in some patients with recurrent VVS.

PMID- 16627440
TI  - Cerebrovascular blood flow during the near syncopal phase of head-up tilt test: a
      comparative study in different types of neurally mediated syncope.
AB  - AIMS: This study analyses the changes in cerebral blood flow (CBF) velocity
      occurring in the near syncopal phase of head-up tilt test (HUT) to determine
      whether their appearance during the premonitory symptoms permits the
      differentiation of the different types of haemodynamic response. METHODS AND
      RESULTS: Six hundred and nineteen patients aged 35.9 +/- 16.4 with a prior
      history of syncope (55%) or presyncope (45%) were studied. Head-up tilt test was
      positive in 585 patients. The test was interrupted before syncope, once
      hypotension was evident and CBF changed. A vasovagal reaction (VVR) was observed
      in 245 patients. They had a 59% fall in diastolic CBF velocity, whereas systolic
      CBF velocity decreased by 12%. Postural orthostatic tachycardia syndrome (POTS)
      was observed in 82, systolic and diastolic CBF velocity decreased 44 and 60%,
      respectively. A similar response was observed in 258 patients with the
      orthostatic intolerance (OI) pattern. No significant changes were observed in the
      negative group. CONCLUSION: Patients with VVR had changes in CBF velocity, which
      are different from those presented by patients with POTS and OI pattern. Cerebral
      blood flow monitoring is useful to increase the yield of HUT and may allow early
      interruption before syncope occurs, reducing patient discomfort.

PMID- 16627441
TI  - Onset mechanism of paroxysmal atrial fibrillation detected by ambulatory Holter
      monitoring.
AB  - AIMS: The aim of this study was to evaluate the mechanisms of induction of
      paroxysmal atrial fibrillation (PAF) by analysis of its onset recorded on Holter
      monitoring (HM). METHODS AND RESULTS: One hundred and seven HM were evaluated in
      90 patients (mean age 67.7, cardiac disease in 31.1%), with one or more self
      terminating episodes of PAF, lasting >or=30 s. Two hundred and thirty-three
      episodes of PAF were detected. A triggering premature atrial complex (PAC) was
      present in 222/233 episodes (95.3%); 118/233 episodes were preceded by a
      bradyarrhythmic event (BE) or a post-extrasystolic pause (50.6%). According to
      the polarity of the ectopic P-wave, triggering PACs were left atrial origin in
      74.3%, right atrial in 15.3%, not determined in 10.4% of cases. Coupling interval
      (CI) of triggering PACs was shorter in episodes preceded by BEs; it was shorter
      than that of non-triggering PACs. Frequency of PACs was significantly higher in
      the hour preceding the onset of PAF. During the day, three periods of higher
      frequency of PAF onsets were found from noon to 2 p.m., 6 p.m. to 2 a.m., and 4
      a.m. to 6 a.m. Heart rate variability analysis showed a vagal prevalence in the 5
      min preceding the onset of arrhythmia, both in the time and in the frequency
      domain. CONCLUSION: Paroxysmal atrial fibrillation is generally triggered by a
      PAC, with left atrial origin in two-thirds of cases: CI and neuroendocrine
      balance are factors affecting the induction of the arrhythmia.

PMID- 16627442
TI  - Utility of adjunctive single oral bolus propafenone therapy in patients with
      atrial defibrillators.
AB  - AIMS: Previous studies have demonstrated that ambulatory atrial defibrillation
      shocks delivered by an implantable cardioverter-defibrillator (ICD) are safe and
      effective, but poorly tolerated. Separate studies have demonstrated the utility
      of single oral bolus propafenone for conversion of recent-onset atrial
      fibrillation (AF); however, most patients were hospitalized, had no structural
      heart disease, were taking no other antiarrhythmic drugs, and were not exposed to
      concomitant shock. We hypothesized that a single oral bolus dose of propafenone
      given early after onset would be a safe and effective adjunct to ICD-based AF
      therapy and improve overall therapy tolerance. METHODS AND RESULTS: A randomized
      three-way crossover study design was used to compare three strategies, deployed
      in the ambulatory setting early after AF episode onset in 35 ICD patients with
      advanced, drug refractory episodic/persistent syndromes, many of whom had
      structural heart disease and were taking other antiarrhythmic drugs: (i) single
      oral bolus propafenone (600 mg), followed by ICD shock if necessary; (ii) single
      oral bolus placebo, followed by ICD shock if necessary; and (iii) no oral bolus
      therapy and ICD shock if necessary (no bolus). Antiarrhythmic efficacy, defined
      by the restoration of sinus rhythm within 24 h, was similar during propafenone
      (81%) and no-bolus strategies (84%); both were significantly higher than during
      placebo strategy (62%). Propafenone was well tolerated and not associated with
      proarrhythmia. Shock use was significantly lower during propafenone strategy
      (19%) than during no-bolus strategy (55%); this was correlated with improved
      patient tolerance. CONCLUSION: Adjunctive use of single oral bolus propafenone is
      safe and effective in patients with an ICD and improves patient tolerance of
      device-based AF therapy.

PMID- 16627443
TI  - Role of ventricular Autocapture function in increasing longevity of DDDR
      pacemakers: a prospective study.
AB  - AIMS: Autocapture is an algorithm for automatic adaptation of ventricular output
      to capture threshold. The aim of this prospective study was to estimate the
      effects of ventricular Autocapture algorithm on DDD-DDDR pacemaker longevity.
      METHODS AND RESULTS: Eighty-three patients implanted with a DDD-DDDR pacemaker
      (Affinity or Entity; St Jude Medical, USA) were enrolled and the Autocapture
      function was activated pre-discharge. Ventricular pulse duration was randomly
      programmed at 0.3 or 0.4 ms, with a cross-over at 8-12 weeks and again at 13-14
      months. Diagnostic data were retrieved from device memory and by calculating
      battery current drain from long-term threshold recordings; device longevity was
      estimated at the following settings: Autocapture with a pulse duration of 0.3 and
      0.4 ms, respectively, standard output (3.5 V, 0.4 ms) and conventional low output
      programming (2.5 V, 0.4 ms). According to a series of assumptions, Autocapture
      was associated with a 55-60% increase in estimated device longevity compared with
      standard output programming and a 6-7% increase in longevity compared with low
      output programming. No significant differences were found between Autocapture
      programmed with a pulse duration of 0.3 or 0.4 ms. In projections to a 10-year
      follow-up, use of the Autocapture function resulted in a 42% reduction in pacing
      related estimated costs compared with standard output programming at 3.5 V, 0.4
      ms. CONCLUSION: Pacing with constant adaptation of ventricular output in dual
      chamber devices has the potential to increase generator longevity and to reduce
      sizeably pacing-related costs compared with standard programming.

PMID- 16627444
TI  - Complete atrioventricular block associated with toxoplasma myocarditis.
AB  - Myocarditis has been described during and after a wide variety of infectious
      agents: viral, rickettsial, bacterial, protozoal, and metazoal diseases may cause
      cardiac inflammation. We report a case of toxoplasma myocarditis in a young
      healthy man.

PMID- 16627445
TI  - Magnetic navigation in AV nodal re-entrant tachycardia study: early results of
      ablation with one- and three-magnet catheters.
AB  - AIMS: Steering soft, flexible catheters using an external magnetic field could
      have advantages for heart catheterization, especially for therapy of
      tachyarrhythmias. Our aims were to assess the feasibility of magnetic navigation
      to Koch's triangle and reliable ablation of atrioventricular nodal re-entry
      tachycardia (AVNRT) with a magnetic catheter. METHODS AND RESULTS: Consecutive
      patients with AVNRT were mapped and ablated with a magnetically enabled catheter
      (Helios I or II), with, respectively, one and three magnets at the tip. The
      catheter was remotely advanced with the Cardiodrive system and orientated with
      the Navigant control system. After initial positioning with the external magnets,
      adjustment was made in 5 degrees steps. Success rates, procedure, and fluoroscopy
      times were analysed, and compared with a local contemporary series of
      conventional AVNRT ablations. Magnetic navigation was feasible in all 20
      patients. Targets were easily reached. Catheters remained stable in position
      during accelerated junctional rhythms. Ablation was successful in 18/20
      procedures (90%). No significant complications occurred. Median patient
      fluoroscopy time was 12 min, median physician fluoroscopy time was 4 min.
      Fluoroscopy times tended to be shorter than that in the conventionally treated
      group. Procedure duration decreased significantly over time, median procedure
      time was similar to that in the conventional group. CONCLUSION: AVNRT can be
      successfully mapped and ablated using magnetic navigation. A learning curve was
      evident, unrelated to catheter type, but to increasing operator experience.
      Physician radiation times were one-third of patient times. No complications
      occurred. Procedure time is comparable with that of conventional ablation.

PMID- 16627446
TI  - Perspectives on the development of a magnetic navigation system for remote
      control of electrophysiology catheters.

PMID- 16627447
TI  - QTc interval and survival in 75-year-old men and women from the general
      population.
AB  - AIMS: The study concerns the relationship of the corrected QT (QTc) interval to
      6.4 years of survival and to measures of cardiac function, such as
      echocardiographic variables and plasma levels of brain natriuretic peptide (BNP),
      in 75-year-old people. METHODS AND RESULTS: QTc was measured in a 12-lead
      electrocardiogram (ECG) in 210 men and 223 women, comprising a randomly selected
      sample from the general population (70% participation rate). The Sicard 440/740
      computer-analysis program, with Hodges' formula for heart rate-based QT
      correction, was used. The optimal cut-off point for predicting survival according
      to the receiver operating characteristic curve was found between 429 and 430 ms.
      Individuals with a QTc interval of > or =430 ms (n = 115) had decreased survival
      when compared with those with shorter QTc interval (n = 318); the relative risk
      was 2.4 (95% confidence interval 1.5-3.7). The predictive ability of QTc reflects
      an association between QTc and the following variables: BNP, left ventricular
      mass, and left ventricular ejection fraction (but not diastolic filling
      patterns). Both Hodges' and Bazett's formulae for heart rate correction of the QT
      interval were useful for predicting survival. The median QTc was 415 ms using
      Hodges' formula and 430 ms with Bazett's formula. The QRS component of QTc
      predicted survival better than the rest of the QTc interval and was approximately
      as useful as the QTc interval itself. CONCLUSION: The computer-derived QTc
      obtained from the ordinary 12-lead ECG identifies high-risk individuals among
      elderly people from the general population.

PMID- 16627448
TI  - Phenotype reveals genotype in a Greek long QT syndrome family.
AB  - We aimed to verify the long QT syndrome (LQTS) genotype in a family with strong
      evidence of LQTS type 1 (LQT1) on the basis of so far established genotype
      phenotype correlations. Genetic testing for mutations in the KCNQ1 potassium
      channel gene revealed an A341V mutation in three generations of the family.
      Existing genotype-phenotype correlations were correctly predictive of the
      genotype in the case of this family, despite the fact that there are no
      previously reported data for the Greek LQTS genetic pool. Thus, genotype
      phenotype correlations are often a helpful tool in the management of LQTS
      patients and their families.

PMID- 16627449
TI  - The left hand as a model for the right atrium: a simple teaching tool.
AB  - AIMS: Knowledge of the complex three-dimensional anatomy of the right atrium is
      mandatory for the electrophysiologist and interventional cardiologist, but its
      understanding remains difficult. We hypothesized that the left hand, loosely
      clenched, is a good three-dimensional model to understand the position of the
      different anatomical and electrical regions in the right atrium. For validation,
      we compared the hand with an endocast that had been prepared from an adult human
      right atrium and with a three-dimensional electro-anatomical CT image of the
      right atrium. METHODS AND RESULTS: Views of the left hand were photographed from
      various angles to replicate as closely as possible the standard fluoroscopic
      views. Using the nomenclature of the bones of the hand, we assigned the different
      regions of the hand to represent regions and structures of the right atrium. An
      endocast was prepared from an adult human right atrium. A three-dimensional
      electro-anatomical right atrial map with CT integration (CartoMerge) was used as
      the gold standard for the exact localization of electrical regions such as the
      sinus node (SN), bundle of His, and slow pathway region. Using the left hand, it
      is possible to mark the free wall, terminal crest, appendage, septal surface,
      oval fossa and orifices of the caval veins, tricuspid valve, and coronary sinus.
      We also marked the anticipated locations of the SN, His bundle, triangle of Koch,
      slow pathway region, inferior isthmus, and right atrial insertion of Bachmann's
      bundle. When compared with an endocast and a three-dimensional electro-anatomical
      CT image, the position and orientation of the marked regions were deemed to be
      anatomically correct. CONCLUSION: Compared with an endocast and a CT-guided
      electro-anatomical reconstruction of the right atrium, the left hand is a
      reliable model to understand the position and orientation of the different
      anatomical and electrical regions in the right atrium. Although an
      oversimplification of the complex right atrial anatomy, this model is 'handy' to
      understand, guide, and teach electrophysiological and interventional procedures.

PMID- 16627450
TI  - Paradoxical effect of ajmaline in a patient with Brugada syndrome.
AB  - AIMS: The typical Brugada ECG pattern consists of a prominent J-wave associated
      with ST-segment elevation localized in the right precordial leads V1-V3. In many
      patients, the ECG presents periods of transient normalization and the Brugada
      phenotype can be unmasked by the administration of class-I antiarrhythmics.
      Reports have documented the heterogeneity of the Brugada syndrome ECG-phenotype
      characterized by unusual localization of the ECG abnormalities in the inferior
      leads. Case report A 51-year-old man, without detectable structural heart
      disease, was referred to us because of a history of syncope, dizziness, and
      palpitations. The ECG showed a J-wave and ST-segment elevation in the right
      precordial leads, suggesting Brugada syndrome. As other causes of the ECG
      abnormalities were excluded, the patient underwent an electrophysiological study
      that documented easy induction of ventricular fibrillation. During infusion of
      ajmaline, new prominent J-waves and ST-segment elevation appeared in the inferior
      leads, whereas the basal ECG abnormalities in the right precordial leads
      normalized. After infusion of isoprenaline, the ECG-pattern resumed the typical
      Brugada pattern. An implantable cardioverter-defibrillator was recommended.
      CONCLUSION: In our patient, the double localization of the typical Brugada
      pattern and the paradoxical effect of ajmaline on the ECG abnormalities confirmed
      the possibility of a phenotype heterogeneity in the Brugada syndrome.

PMID- 16627451
TI  - Long-term continuous external electrocardiographic recording: a review.
AB  - Ambulatory electrocardiographic (AECG) monitoring is an essential tool in the
      diagnostic evaluation of patients with cardiac arrhythmias. Recent advances in
      solid-state technology have improved the quality of the ECG signals and new
      dedicated algorithms have expanded the clinical application of software-based
      AECG analysis systems. These advances, in addition to the availability of
      inexpensive large storage capacities, and very long-term continuous high-quality
      AECG monitoring, have opened new potential uses for AECG. New digital recorders
      have the capability of multichannel simultaneous recordings (from 3 to 12 leads)
      and for telemetred signal transduction. These possibilities will expand the
      traditional uses of AECG for arrhythmia detection, as arrhythmia monitoring to
      assess drug and device efficacies has been further defined by new studies. The
      analysis of transient ST-segment deviation still remains controversial, but
      considerably more data are now available, especially about the prognostic value
      of detecting asymptomatic ischaemia. Heart rate variability analysis has shown
      promise for predicting mortality rates in cardiac patients at high risk. We
      review recent advances in this field of non-invasive cardiac testing.

PMID- 16627452
TI  - Cardiac resynchronization therapy for adult congenital heart disease patients
      with a systemic right ventricle: analysis of feasibility and review of early
      experience.
AB  - AIMS: Patients with a systemic right ventricle (RV) frequently develop heart
      failure and may benefit from cardiac resynchronization therapy (CRT). We aimed to
      assess the proportion of unselected patients with a systemic RV eligible for CRT
      and to review available data on the effect of CRT in congenital heart disease
      patients. METHODS AND RESULTS: Adhering to criteria derived from landmark CRT
      trials, we determined the eligibility of patients with a systemic RV for CRT.
      Seventy-five transposition of the great arteries (TGA) patients (age 29.5+/-10.2
      years) and 49 patients with congenitally corrected (cc) TGA (age 36.2+/-12.8
      years) were studied. Full criteria for CRT were met in 4.0% of the TGA patients
      and 4.1% of the ccTGA patients. Including New York Heart Association class 2
      patients, 9.3% of TGA and 6.1% of ccTGA patients were eligible for CRT.
      CONCLUSION: Four to 9% of unselected patients with a systemic RV appear to be
      potential candidates for CRT. Although large clinical studies are currently
      lacking, available data consistently demonstrate that CRT improves haemodynamics
      in congenital heart disease patients and warrants further investigation.

PMID- 16627453
TI  - The influence of fluid and diuretic administration on the index of atrial
      contribution in sequentially paced patients.
AB  - AIMS: To examine whether acute changes in patient hydration can change atrial
      contribution (AC) to circulatory function. METHODS AND RESULTS: Atrial
      contribution was quantified by beat-to-beat changes in the amplitude of pulse
      oximetry signal in 24 paced outpatients. Changes in body weight were used for
      assessment of changes in total body water. The first measurement was performed at
      steady state. The second measurement was made after infusion of saline (5 mL/kg)
      and the third measurement was obtained 2 h after a bolus of furosemide (1 mg/kg).
      Changes found after furosemide administration (compared with steady state): a
      substantial decrease in body weight from median 78.6 (interquartile range 65.7
      86.5) to 77.1 (64.4-85.6) kg (P < 0.001), accompanied by an increase in AC from
      30.4 (20.2-47.1) up to 43.3 (30.6-80.9)% (P < 0.001). An increase in heart rate
      and shortening of the atrioventricular conduction time occurred during acute
      hypohydration in some of the subjects. CONCLUSION: Administration of furosemide
      was followed by a decrease in body weight and an increase in AC to stroke volume.
      This suggests that in conditions where pre-load is reduced cardiac output is
      preserved by an increase in AC enforced by sympathetic activation.

PMID- 16627454
TI  - Electromechanical synchronization of the heterotopic and native heart by dual
      atrial stimulation following heart transplantation.
AB  - After heterotopic heart transplantation, a 59-year-old woman presented with
      remarkable symptoms of breathlessness and fatigue, despite excellent donor heart
      function. Asynchrony of donor and native heart provoked haemodynamic instability.
      Dual atrial pacemaker implantation lead to linkage and synchronization of atrial
      and ventricular contraction in both the donor and native heart with the faster
      organ executing the synchronization. Remarkable relief of symptoms has been
      evident during the long-term follow-up.

PMID- 16627455
TI  - Post-operative use of heparin increases morbidity of pacemaker implantation.
AB  - AIMS: The objective of this study is to characterize the incidence of peri
      operative severe adverse events (AEs) related to the post-operative use of
      heparin in patients undergoing pacemaker surgery. METHODS AND RESULTS: We
      retrospectively compared the outcome of 38 patients with mechanical valves (MVs)
      and 76 patients with atrial fibrillation (AF) with control cases matched for
      gender, age, and surgical details. Heparin was systematically used post
      operatively in MV patients, but left to clinical judgment in AF patients. The
      relative risk for severe haemorrhagic AEs was 11 (CI 1.5-81.1, P < 0.01) in the
      MV group when compared with matched controls and 8 (CI 1.0-62.5, P < 0.05) in the
      AF group. Overall, the relative risk of heparin use in the post-operative period
      was 14 (CI 1.88-104, P = 0.0006) and the post-operative stay was prolonged from 7
      days in this group when compared with control cases (P < 0.0001).The variables
      associated with haemorrhage were the delay to restart heparin after surgery and
      the presence of an MV. CONCLUSION: Post-operative use of heparin increases
      morbidity of pacemaker implantation. A different approach to management of these
      patients is possible.

PMID- 16627456
TI  - The RIONI study rationale and design: validation of the first stored electrograms
      transmitted via home monitoring in patients with implantable defibrillators.
AB  - Appropriate and inappropriate therapies of implantable cardioverter
      defibrillators (ICDs) have a major impact on morbidity and quality of life in ICD
      recipients. The recently introduced home monitoring of ICD devices is a promising
      new technique which remotely offers information about the status of the system.
      Stored intracardiac electrograms (IEGMs), which are essential for correct
      classification of appropriate and inappropriate ICD discharges, have until now
      not been available with ICD home monitoring on a day-by-day basis because of
      limitations of transferable data. We demonstrate the first compressed IEGMs daily
      transferable via home monitoring (IEGM-online). Validation of these electrograms
      will be performed in the Reliability of IEGM-Online Interpretation (RIONI) study.
      A total of 210 episodes of stored IEGMs will be collected by at least 12 European
      centres. The primary endpoint of this study is to investigate whether the IEGM
      online based evaluation of the appropriateness of the ICDs therapeutic decision
      following episode detection is equivalent to the evaluation based on the complete
      ICD episode Holter extracted from the IEGM stored. The evaluation is
      independently done by an expert board of three experienced ICD investigators. The
      equivalence of the two methods is accepted if the evaluations yield a different
      conclusion for <10% of all evaluated IEGMs. The conclusion of the study is
      expected at the beginning of 2007. If RIONI successfully validates IEGMs
      transmitted via home monitoring, a strong basis for the use of this promising
      technique will be established.

PMID- 16627457
TI  - Unipolar ventricular pacing reduces inappropriate shocks from a separate
      cardioverter defibrillator in a post-Fontan patient.
AB  - This report describes a 20-year-old man with complex congenital heart disease and
      inappropriate epicardial implantable cardioverter defibrillator (ICD) shocks
      secondary to double counting of ventricular-paced spikes and QRS complexes from a
      separate bipolar epicardial dual-chamber pacemaker. Adjusting to a unipolar paced
      ventricular mode resolved any double counting via pacemaker-ICD interaction.

PMID- 16627458
TI  - A simple point score system for predicting the efficacy of external rectilinear
      biphasic cardioversion for persistent atrial fibrillation.
AB  - AIMS: To develop a simple point score system that can accurately predict the
      optimal energy of initial rectilinear biphasic (RLB) waveform shock for
      cardioversion (DC) of persistent atrial fibrillation (AF). METHODS AND RESULTS:
      Data from 302 consecutive patients with AF who underwent a step-up protocol of
      sequential shocks of 50 J-from 1 up to 2 J/kg-200 J of RLB waveform DC were
      prospectively examined. Using a logistic regression model, three variables
      independently predicted the need for 2 J/kg shocks: AF duration > 7 months,
      previous DC, and increased left atrial (LA) diameter > 4.5 cm. A simplified point
      score system (REBICAF score) that spans from 0 to 4 was developed. The score
      gives two points for AF duration > 7 months and one point for previous DC or LA
      diameter > 4.5 cm. The area under the receiver operator curve (ROC) of the
      proposed score for predicting the need for 2 J/kg shock was 0.84. There was a
      progressive increase in the need for 1 J/kg, 2 J/kg, and 200 J as the point score
      increased (P < 0.001, chi2 test for trend). More than 90% cumulative success rate
      was achieved in the low- (0-1), intermediate- (2), and high-REBICAF (3-4) score
      subgroups with 1 J/kg, 2 J/kg, and 200 J RLB shocks, respectively. CONCLUSION: A
      simple point score system is useful in prediction of successful initial RLB
      energy for DC of AF.

PMID- 16627459
TI  - Design and rationale of a randomized study to compare amiodarone and Class IC
      anti-arrhythmic drugs in terms of atrial fibrillation treatment efficacy in
      patients paced for sinus node disease: the PITAGORA trial.
AB  - AIMS: Many sinus node disease (SND) patients suffer from atrial fibrillation
      (AF). Anti-arrhythmic drugs (AADs) are the therapeutic mainstay for AF
      prophylaxis. The PITAGORA trial has a multicentre, prospective, randomized,
      single blind design to compare amiodarone with Class IC AADs in patients who have
      an AF history and are paced for SND. METHODS AND RESULTS: Starting from January
      2001, 176 patients received a Medtronic AT500 pacemaker. AADs were randomly
      assigned with a 3 : 2 ratio between Class III and Class IC. Randomization was
      stratified in order to assign two patients to amiodarone and one patient to
      sotalol every three Class III AAD patients. After a 5-month observational period,
      Ramp or Burst+ ATP therapies were enabled in a randomized way, maintained for 4
      months, and then crossed over. Total follow-up period is 21 months. The primary
      long-term objective is to show the non-inferiority of IC AADs compared with
      amiodarone in terms of time to first occurrence of a composite endpoint (death,
      atrial cardioversion, hospitalizations due to AF or heart failure, or change of
      AADs). Data will be analysed on an intention-to-treat basis. The primary short
      term objective is to compare Ramp vs. Burst+ efficacy in terminating atrial
      tachyarrhythmias treated by the device. Secondary endpoints are major clinical
      events, medication toxicity, symptoms, AF burden, and quality-of-life.
      CONCLUSION: Given the high morbidity and healthcare costs associated with AF, new
      therapeutic strategies are needed. The results of the PITAGORA trial may help in
      guiding AADs therapy and ATP programming in SND patients suffering from AF.

PMID- 16627460
TI  - Central serotoninergic response to orthostatic challenge in patients with
      neurocardiogenic syncope.
AB  - AIMS: To determine whether central serotoninergic system activity is impaired by
      orthostatic challenge in patients with neurocardiogenic syncope (NCS). METHODS
      AND RESULTS: Thirty-five [mean age: 24 (SD): 6 years] patients with a clinical
      history of NCS and positive head-up tilt test and 35 age-matched healthy
      volunteers (CON = 25+/-5 years) with negative response were studied. Overnight
      dexamethasone suppression test (DST) (1.5 mg given at 11 p.m.) was performed to
      assess the sensitivity of the hypothalamic-pituitary-adrenal axis by measuring
      next day cortisol (microg/dL) at 8 a.m. and 4 p.m. Cardiac autonomic function,
      cortisol, and prolactin (ng/dL) were also determined at baseline supine (BAS) and
      after 5, 10, and 15 min of orthostatic stress (OS) at 60 degrees . No significant
      differences were observed in cortisol plasma levels after the DST: CON = 0.6+/
      0.6 microg/dL vs. NCS = 0.6+/-0.5; P = 0.7. Cardiac autonomic function, cortisol,
      and prolactin responses were similar in both study groups (CON vs. NCS; P > 0.05)
      during BAS: cortisol = 8.6+/-4 vs.8.7+/-4 microg/dL and prolactin = 16.8+/-9 vs.
      16.8+/-9 ng/dL; OS-5: cortisol = 8.7+/-5 vs. 8.5+/-4 microg/dL and prolactin =
      16.9+/-9 vs. 15.8+/-9 ng/dL; OS-10: cortisol = 8.5+/-5 vs. 8.1+/-3 microg/dL;
      prolactin = 16.2+/-9 vs. 15.8+/-9 ng/dL, and OS-15: cortisol = 9.0+/-5 vs. 8.4+/
      4 microg/dL; prolactin = 17.1+/-9 vs. 15.5+/-9 ng/dL. CONCLUSION: Central
      serotoninergic response during orthostatic challenge was not impaired in patients
      with recurrent NCS. These findings suggest that the activation of the
      hypothalamic-pituitary-adrenal axis is not altered in patients with recurrent
      NCS.

PMID- 16627461
TI  - Neuropsychological sequelae of bacterial meningitis: the influence of alcoholism
      and adjunctive dexamethasone therapy.

PMID- 16627464
TI  - Challenges of marijuana research.

PMID- 16627465
TI  - Familial risk for Alzheimer's disease alters fMRI activation patterns.
AB  - Alzheimer's disease poses a looming crisis for the health care system as well as
      society in general. The low efficacy of current treatments for those already
      affected with this disease has prompted the suggestion that interventions might
      be more successful if they were applied before the development of significant
      pathology, that is, when individuals are clinically asymptomatic. Currently, the
      field requires a sensitive and specific diagnostic tool for identifying those
      individuals destined to develop this disease. As a first step, we present here an
      analysis of cross-sectional data for 95 asymptomatic offspring (50-75 years of
      age) of autopsy-confirmed late-onset familial Alzheimer's disease cases and 90
      age-matched controls, studied with functional magnetic resonance imaging (fMRI)
      to investigate brain activation patterns. Analysis of activation in response to a
      paired-associates memory paradigm found significantly different patterns in these
      groups. At-risk individuals showed more intense and extensive activation in the
      frontal and temporal lobes including the hippocampus during memory encoding, an
      increase unrelated to the APOE epsilon4 allele. They also showed decreased
      activation particularly in the cingulum and thalamus during both the encoding and
      recall phases of the task. These results demonstrate that asymptomatic
      individuals, at genetic risk for development of late-onset Alzheimer's disease by
      virtue of familial clustering, show functional activation patterns distinct from
      those without such risk more than a decade before their parent's onset age. While
      longitudinal study is needed to determine whether these patterns, or a subset of
      them, are predictive of disease onset, these findings suggest that functional
      neuroimaging holds promise as a method of identifying pre-clinical Alzheimer's
      disease.

PMID- 16627466
TI  - Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1.
AB  - Nerve growth factor (NGF) and the ubiquitous second messenger cyclic AMP (cAMP)
      are both implicated in neuronal differentiation. Multiple studies indicate that
      NGF signals to at least a subset of its targets via cAMP, but the link between
      NGF and cAMP has remained elusive. Here, we have described the use of small
      molecule inhibitors to differentiate between the two known sources of cAMP in
      mammalian cells, bicarbonate- and calcium-responsive soluble adenylyl cyclase
      (sAC) and G protein-regulated transmembrane adenylyl cyclases. These inhibitors,
      along with sAC-specific small interfering RNA, reveal that sAC is uniquely
      responsible for the NGF-elicited rise in cAMP and is essential for the NGF
      induced activation of the small G protein Rap1 in PC12 cells. In contrast and as
      expected, transmembrane adenylyl cyclase-generated cAMP is responsible for Rap1
      activation by the G protein-coupled receptor ligand PACAP (pituitary adenylyl
      cyclase-activating peptide). These results identify sAC as a mediator of NGF
      signaling and reveal the existence of distinct pathways leading to cAMP-dependent
      signal transduction.

PMID- 16627467
TI  - A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic
      elastase-like serine proteases.
AB  - Serpins form a large class of protease inhibitors involved in regulation of a
      wide spectrum of physiological processes. Recently identified prokaryotic members
      of this protein family may provide a key to the evolutionary origins of the
      unique serpin fold and the associated inhibitory mechanism. We performed a
      biochemical characterization of a serpin from Bifidobacterium longum, an
      anaerobic Gram-positive bacterium that naturally colonizes human gastrointestinal
      tract. The B. longum serpin was shown to efficiently inhibit eukaryotic elastase
      like proteases with a stoichiometry of inhibition close to 1. Porcine pancreatic
      elastase and human neutrophil elastase were inhibited with the second order
      association constants of 4.7 x 10(4) m(-1) s(-1) and 2.1 x 10(4) m(-1) s(-1),
      respectively. The B. longum serpin is expected to be active in the
      gastrointestinal tract, because incubation of the purified recombinant serpin
      with mouse feces produces a stable covalent serpin-protease adduct readily
      detectable by SDS-PAGE. Bifidobacteria may encounter both pancreatic elastase and
      neutrophil elastase in their natural habitat and protection against exogenous
      proteolysis may play an important role in the interaction between these commensal
      bacteria and their host.

PMID- 16627468
TI  - Structural and functional characterization of an essential RTX subdomain of
      Bordetella pertussis adenylate cyclase toxin.
AB  - The adenylate cyclase toxin (CyaA) is one of the major virulence factors of
      Bordetella pertussis, the causative agent of whooping cough. CyaA is able to
      invade eukaryotic cells by a unique mechanism that consists in a calcium
      dependent, direct translocation of the CyaA catalytic domain across the plasma
      membrane of the target cells. CyaA possesses a series of a glycine- and aspartate
      rich nonapeptide repeats (residues 1006-1613) of the prototype
      GGXG(N/D)DX(L/I/F)X (where X represents any amino acid) that are characteristic
      of the RTX (repeat in toxin) family of bacterial cytolysins. These repeats are
      arranged in a tandem fashion and may fold into a characteristic parallel beta
      helix or beta-roll motif that constitutes a novel type of calcium binding
      structure, as revealed by the three-dimensional structure of the Pseudomonas
      aeruginosa alkaline protease. Here we have characterized the structure-function
      relationships of various fragments from the CyaA RTX subdomain. Our results
      indicate that the RTX functional unit includes both the tandem repeated
      nonapeptide motifs and the adjacent polypeptide segments, which are essential for
      the folding and calcium responsiveness of the RTX module. Upon calcium binding to
      the RTX repeats, a conformational rearrangement of the adjacent non-RTX sequences
      may act as a critical molecular switch to trigger the CyaA entry into target
      cells.

PMID- 16627469
TI  - Inhibition of the mitotic kinesin Eg5 up-regulates Hsp70 through the
      phosphatidylinositol 3-kinase/Akt pathway in multiple myeloma cells.
AB  - The microtubule-dependent motor protein Eg5 plays a critical role in spindle
      assembly and maintenance in mitosis. Herein we show that the suppression of Eg5
      by a specific inhibitor arrested mitosis, induced apoptosis, and up-regulated
      Hsp70 in human multiple myeloma cells. Mechanistically, Hsp70 induction occurred
      at the transcriptional level via a cis-regulatory DNA element in Hsp70 promoter
      and was mediated by the phosphatidylinositol 3-kinase/Akt pathway. Eg5 inhibitor
      mediated Hsp70 up-regulation is cytoprotective because blocking Hsp70 induction
      directly by antisense or small interfering RNA or indirectly by inhibiting the
      phosphatidylinositol 3-kinase/Akt pathway significantly increased Eg5 inhibitor
      induced apoptosis. Furthermore, a farnesyltransferase inhibitor interacted
      synergistically with the Eg5 inhibitor in inducing apoptosis through disrupting
      the Akt/Hsp70 signaling axis. These findings provide the first evidence for Eg5
      inhibitor activity in hematologic malignancy and identify Hsp70 up-regulation as
      a critical mechanism responsible for modulating myeloma cell sensitivity to Eg5
      inhibitors. In addition, these findings suggest that a combination of Eg5
      inhibitors with agents abrogating Hsp70 induction would be useful for myeloma
      therapy in the clinic.

PMID- 16627470
TI  - An asymmetric contribution to gamma-aminobutyric type A receptor function of a
      conserved lysine within TM2-3 of alpha1, beta2, and gamma2 subunits.
AB  - Mutations that impair the expression and/or function of gamma-aminobutyric acid
      type A (GABAA) receptors can lead to epilepsy. The familial epilepsy
      gamma2(K289M) mutation affects a basic residue conserved in the TM2-3 linker of
      most GABAA subunits. We investigated the effect on expression and function of the
      Lys --> Met mutation in mouse alpha1(K278M), beta2(K274M), and gamma2(K289M)
      subunits. Compared with cells expressing wild-type and alpha1beta2gamma2(K289M)
      receptors, cells expressing alpha1(K278M)beta2gamma2 and alpha1beta2(K274M)gamma2
      receptors exhibited reduced agonist-evoked current density and reduced GABA
      potency, with no change in single channel conductance. The low current density of
      alpha1beta2(K274M)gamma2 receptors coincided with reduced surface expression. By
      contrast the surface expression of alpha1(K278M)beta2gamma2 receptors was similar
      to wild-type and alpha1beta2gamma2(K289M) receptors suggesting that the
      alpha1(K278M) impairs function. In keeping with this interpretation GABA
      activated channels mediated by alpha1(K278M)beta2gamma2 receptors had brief open
      times. To a lesser extent gamma2(K289M) also reduced mean open time, whereas
      beta2(K274M) had no effect. We used propofol as an alternative GABAA receptor
      agonist to test whether the functional deficits of mutant subunits were specific
      to GABA activation. Propofol was less potent as an activator of
      alpha1(K278M)beta2gamma2 receptors. By contrast, neither beta2(K274M) nor
      gamma2(K289M) affected the potency of propofol. The beta2(K274M) construct was
      unique in that it reduced the efficacy of propofol activation relative to GABA.
      These data suggest that the alpha1 subunit Lys-278 residue plays a pivotal role
      in channel gating that is not dependent on occupancy of the GABA binding site.
      Moreover, the conserved TM2-3 loop lysine has an asymmetric function in different
      GABAA subunits.

PMID- 16627471
TI  - ADP-ribosyltransferase-specific modification of human neutrophil peptide-1.
AB  - Epithelial cells lining human airways and cells recruited to airways participate
      in the innate immune response in part by releasing human neutrophil peptides
      (HNP). Arginine-specific ADP-ribosyltransferases (ART) on the surface of these
      cells can catalyze the transfer of ADP-ribose from NAD to proteins. We reported
      that ART1, a mammalian ADP-ribosyltransferase, present in epithelial cells lining
      the human airway, modified HNP-1, altering its function. ADP-ribosylated HNP-1
      was identified in bronchoalveolar lavage fluid (BALF) from patients with asthma,
      idiopathic pulmonary fibrosis, or a history of smoking (and having two common
      polymorphic forms of ART1 that differ in activity), but not in normal volunteers
      or patients with lymphangioleiomyomatosis. Modified HNP-1 was not found in the
      sputum of cystic fibrosis patients or in leukocyte granules of normal volunteers.
      The finding of ADP-ribosyl-HNP-1 in BALF but not in leukocyte granules suggests
      that the modification occurred in the airway. Most of the HNP-1 in the BALF from
      individuals with a history of smoking was, in fact, mono- or di-ADP-ribosylated.
      ART1 synthesized in Escherichia coli, glycosylphosphatidylinositol-anchored ART1
      released with phosphatidylinositol-specific phospholipase C from transfected NMU
      cells, or ART1 expressed endogenously on C2C12 myotubes modified arginine 14 on
      HNP-1 with a secondary site on arginine 24. ADP-ribosylation of HNP-1 by ART1 was
      substantially greater than that by ART3, ART4, ART5, Pseudomonas aeruginosa
      exoenzyme S, or cholera toxin A subunit. Mouse ART2, which is an NAD:arginine ADP
      ribosyltransferase, was able to modify HNP-1, but to a lesser extent than ART1.
      Although HNP-1 was not modified to a significant degree by ART5, it inhibited
      ART5 as well as ART1 activities. Human beta-defensin-1 (HBD1) was a poor
      transferase substrate. Reduction of the cysteine-rich defensins enhanced their
      ability to serve as ADP-ribose acceptors. We conclude that ADP-ribosylation of
      HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory
      conditions and disease.

PMID- 16627472
TI  - PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular
      localization of TRPV4.
AB  - TRPV4 is a cation channel that responds to a variety of stimuli including
      mechanical forces, temperature, and ligand binding. We set out to identify TRPV4
      interacting proteins by performing yeast two-hybrid screens, and we isolated with
      the avian TRPV4 amino terminus the chicken orthologues of mammalian PACSINs 1 and
      3. The PACSINs are a protein family consisting of three members that have been
      implicated in synaptic vesicular membrane trafficking and regulation of dynamin
      mediated endocytotic processes. In biochemical interaction assays we found that
      all three murine PACSIN isoforms can bind to the amino terminus of rodent TRPV4.
      No member of the PACSIN protein family was able to biochemically interact with
      TRPV1 and TRPV2. Co-expression of PACSIN 3, but not PACSINs 1 and 2, shifted the
      ratio of plasma membrane-associated versus cytosolic TRPV4 toward an apparent
      increase of plasma membrane-associated TRPV4 protein. A similar shift was also
      observable when we blocked dynamin-mediated endocytotic processes, suggesting
      that PACSIN 3 specifically affects the endocytosis of TRPV4, thereby modulating
      the subcellular localization of the ion channel. Mutational analysis shows that
      the interaction of the two proteins requires both a TRPV4-specific proline-rich
      domain upstream of the ankyrin repeats of the channel and the carboxyl-terminal
      Src homology 3 domain of PACSIN 3. Such a functional interaction could be
      important in cell types that show distribution of both proteins to the same
      subcellular regions such as renal tubule cells where the proteins are associated
      with the luminal plasma membrane.

PMID- 16627473
TI  - Crystal structure of the severe acute respiratory syndrome (SARS) coronavirus
      nucleocapsid protein dimerization domain reveals evolutionary linkage between
      corona- and arteriviridae.
AB  - The causative agent of severe acute respiratory syndrome (SARS) is the SARS
      associated coronavirus, SARS-CoV. The nucleocapsid (N) protein plays an essential
      role in SARS-CoV genome packaging and virion assembly. We have previously shown
      that SARS-CoV N protein forms a dimer in solution through its C-terminal domain.
      In this study, the crystal structure of the dimerization domain, consisting of
      residues 270-370, is determined to 1.75A resolution. The structure shows a dimer
      with extensive interactions between the two subunits, suggesting that the dimeric
      form of the N protein is the functional unit in vivo. Although lacking
      significant sequence similarity, the dimerization domain of SARS-CoV N protein
      has a fold similar to that of the nucleocapsid protein of the porcine
      reproductive and respiratory syndrome virus. This finding provides structural
      evidence of the evolutionary link between Coronaviridae and Arteriviridae,
      suggesting that the N proteins of both viruses have a common origin.

PMID- 16627474
TI  - Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA
      double strand breaks in human neuron-like cells.
AB  - The protein kinase ATM (ataxia-telangiectasia mutated) activates the cellular
      response to double strand breaks (DSBs), a highly cytotoxic DNA lesion. ATM is
      activated by DSBs and in turn phosphorylates key players in numerous damage
      response pathways. ATM is missing or inactivated in the autosomal recessive
      disorder ataxia-telangiectasia (A-T), which is characterized by neuronal
      degeneration, immunodeficiency, genomic instability, radiation sensitivity, and
      cancer predisposition. The predominant symptom of A-T is a progressive loss of
      movement coordination due to ongoing degeneration of the cerebellar cortex and
      peripheral neuropathy. A major deficiency in understanding A-T is the lack of
      information on the role of ATM in neurons. It is unclear whether the ATM-mediated
      DSB response operates in these cells similarly to proliferating cells.
      Furthermore, ATM was reported to be cytoplasmic in neurons and suggested to
      function in these cells in capacities other than the DNA damage response.
      Recently we obtained genetic molecular evidence that the neuronal degeneration in
      A-T does result from defective DNA damage response. We therefore undertook to
      investigate this response in a model system of human neuron-like cells (NLCs)
      obtained by neuronal differentiation in culture. ATM was largely nuclear in NLCs,
      and their ATM-mediated responses to DSBs were similar to those of proliferating
      cells. Knocking down ATM did not interfere with neuronal differentiation but
      abolished ATM-mediated damage responses in NLCs. We concluded that nuclear ATM
      mediates the DSB response in NLCs similarly to in proliferating cells. Attempts
      to understand the neurodegeneration in A-T should be directed to investigating
      the DSB response in the nervous system.

PMID- 16627475
TI  - Second messenger function of nicotinic acid adenine dinucleotide phosphate
      revealed by an improved enzymatic cycling assay.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent
      activator of Ca2+ release from intracellular stores known today. Although recent
      reports have suggested an important function of NAADP in human T lymphocytes,
      direct evidence for receptor-induced formation of NAADP is yet missing in these
      cells. Thus, we developed a highly sensitive and specific enzyme assay capable of
      quantifying low fmol amounts of NAADP. In unstimulated T cells, the NAADP
      concentration amounted to 4.4 +/- 1.6 nm (0.055 +/- 0.028 pmol/mg of protein).
      Stimulation of the cells via the T cell receptor/CD3 complex resulted in biphasic
      elevation kinetics of cellular NAADP levels and was characterized by a bell
      shaped concentration-response curve for NAADP. In contrast, the NAADP
      concentration was elevated neither upon activation of the ADP-ribose/TRPM2
      channel Ca2+ signaling system nor by an increase of the intracellular Ca2+
      concentration upon thapsigargin stimulation. T cell receptor/CD3 complex-mediated
      NAADP formation was dependent on the activity of tyrosine kinases because
      genistein completely blocked NAADP elevation. Thus, we propose a regulated
      formation of NAADP upon specific stimulation of the T cell receptor/CD3 complex,
      suggesting a function of NAADP as a Ca2+-mobilizing second messenger during T
      cell activation.

PMID- 16627476
TI  - Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a
      genetic reporter system.
AB  - p94/calpain 3 is a skeletal muscle-specific member of the Ca(2+)-regulated
      cytosolic cysteine protease family, the calpains. Defective p94 protease activity
      originating from gene mutations causes a muscular dystrophy called calpainopathy,
      indicating the indispensability of p94 for muscle survival. Because of the
      existence of the p94-specific regions IS1 and IS2, p94 undergoes very rapid and
      exhaustive autolysis. To elucidate the physiological relevance of this unique
      activity, the autolytic profiles of p94 and the effect of the p94 binding
      protein, connectin/titin, on this process were investigated. In vitro analysis of
      p94 autolysis showed that autolysis in IS1 proceeds without immediate disassembly
      into fragments and that the newly identified cryptic autolytic site in IS2 is
      critical for disassembling autolyzed fragments. As a genetic system to assay p94
      autolysis semiquantitatively, p94 was expressed in yeast as a hybrid protein
      between the DNA binding and activation domains of the yeast transcriptional
      activator Gal4. Transcriptional activation by the Gal4-p94:WT hybrid protein is
      precluded by p94 autolysis. Complete or partial loss of autolytic activity by
      C129S active site mutation, limb girdle muscular dystrophy type 2A pathogenic
      missense mutations, or PCR-based random mutagenesis could be detected by
      semiquantitative restoration of Gal4-dependent beta-galactosidase gene
      expression. Using this system, the N2A connectin fragment that binds to p94 was
      shown to suppress p94 autolytic disassembly. The proximity of the IS2 autolytic
      and connectin-binding sites in p94 suggested that N2A connectin suppresses IS2
      autolysis. These data indicate the importance of p94-connectin interaction in the
      control of p94 functions by regulating autolytic decay of p94.

PMID- 16627477
TI  - Molecular analysis of ulilysin, the structural prototype of a new family of
      metzincin metalloproteases.
AB  - The metzincin clan encompasses several families of zinc-dependent
      metalloproteases with proven function both in physiology and pathology. They act
      either as broad spectrum protein degraders or as sheddases, operating through
      limited proteolysis. Among the structurally uncharacterized metzincin families
      are the pappalysins, of which the most thoroughly studied member is human
      pregnancy-associated plasma protein A (PAPP-A), a heavily glycosylated 170-kDa
      multidomain protein specifically cleaving insulin-like growth factor (IGF)
      binding proteins (IGFBPs). Proulilysin is a 38-kDa archaeal protein that shares
      sequence similarity with PAPP-A but encompasses only the pro-domain and the
      catalytic domain. It undergoes calcium-mediated autolytic activation, and the
      mature protein adopts a three-dimensional structure with two subdomains separated
      by an active site cleft containing the catalytic zinc ion. This structure is
      reminiscent of human members of the adamalysin/ADAMs (a disintegrin and a
      metalloprotease) family of metzincins. A bound dipeptide yields information on
      the substrate specificity of ulilysin, which specifically hydrolyzes IGFBP-2 to 
      6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II.
      Accordingly, ulilysin has higher proteolytic efficiency and a broader substrate
      specificity than human PAPP-A. The structure of ulilysin represents a prototype
      for the catalytic domain of pappalysins.

PMID- 16627478
TI  - O-glycosylation regulates autolysis of cellular membrane type-1 matrix
      metalloproteinase (MT1-MMP).
AB  - MT1-MMP is a key enzyme in cancer cell invasion and metastasis. The activity of
      cellular MT1-MMP is regulated by furin-like proprotein convertases, TIMPs,
      shedding, autoproteolysis, dimerization, exocytosis, endocytosis, and recycling.
      Our data demonstrate that, in addition to these already known mechanisms, MT1-MMP
      is regulated by O-glycosylation of its hinge region. Insignificant autolytic
      degradation is characteristic for naturally expressed, glycosylated, MT1-MMP. In
      turn, extensive autolytic degradation, which leads to the inactivation of the
      protease and the generation of its C-terminal membrane-tethered degraded species,
      is a feature of overexpressed MT1-MMP. We have determined that incomplete
      glycosylation stimulates extensive autocatalytic degradation and self
      inactivation of MT1-MMP. Self-proteolysis commences during the secretory process
      of MT1-MMP through the cell compartment to the plasma membrane. The strongly
      negatively charged sialic acid is the most important functional moiety of the
      glycopart of MT1-MMP. We hypothesize that sialic acid of the O-glycosylation
      cassette restricts the access of the catalytic domain to the hinge region and to
      the autolytic cleavage site and protects MT1-MMP from autolysis. Overall, our
      results point out that there is a delicate balance between glycosylation and self
      proteolysis of MT1-MMP in cancer cells and that when this balance is upset the
      catalytically potent MT1-MMP pool is self-proteolyzed.

PMID- 16627479
TI  - The structure of the human centrin 2-xeroderma pigmentosum group C protein
      complex.
AB  - Human centrin-2 plays a key role in centrosome function and stimulates nucleotide
      excision repair by binding to the xeroderma pigmentosum group C protein. To
      determine the structure of human centrin-2 and to develop an understanding of
      molecular interactions between centrin and xeroderma pigmentosum group C protein,
      we characterized the crystal structure of calcium-loaded full-length centrin-2
      complexed with a xeroderma pigmentosum group C peptide. Our structure shows that
      the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium
      atoms, whereas the amino-terminal lobe is in a closed conformation positioned
      distantly by an ordered alpha-helical linker. A stretch of the amino-terminal
      domain unique to centrins appears disordered. Two xeroderma pigmentosum group C
      peptides both bound to centrin-2 also interact to form an alpha-helical coiled
      coil. The interface between centrin-2 and each peptide is predominantly nonpolar,
      and key hydrophobic residues of XPC have been identified that lead us to propose
      a novel binding motif for centrin.

PMID- 16627480
TI  - The genetic stability of a conditional live HIV-1 variant can be improved by
      mutations in the Tet-On regulatory system that restrain evolution.
AB  - Live attenuated human immunodeficiency virus type 1 (HIV-1) vaccines are
      considered unsafe because more quickly replicating pathogenic virus variants may
      evolve after vaccination. As an alternative vaccine approach, we have previously
      presented a doxycycline (dox)-dependent HIV-1 variant that was constructed by
      incorporating the tetracycline-inducible gene expression system (Tet-On system)
      into the viral genome. Replication of this HIV-rtTA variant is driven by the dox
      inducible transcriptional activator rtTA and can be switched on and off at will.
      A large scale evolution study was performed to test the genetic stability of this
      conditional live vaccine candidate. In several long term cultures, we selected
      for HIV-rtTA variants that no longer required dox for replication. These evolved
      variants acquired a typical amino acid substitution either at position 19 or 37
      in the rtTA protein. Both mutations caused rtTA activity and viral replication in
      the absence of dox. We designed a novel rtTA variant with a higher genetic
      barrier toward these undesired evolutionary routes. The corresponding HIV-rtTA
      variant did not lose dox control in long term cultures, demonstrating its
      improved genetic stability.

PMID- 16627481
TI  - Thrombin-induced autoinhibitory factor, Down syndrome critical region-1,
      attenuates NFAT-dependent vascular cell adhesion molecule-1 expression and
      inflammation in the endothelium.
AB  - Activation and dysfunction of the endothelium underlie many vascular disorders
      including atherosclerosis, tumor growth, and inflammation. We recently reported
      that thrombin and vascular endothelial growth factor, but not tumor necrosis
      factor-alpha, results in dramatic up-regulation of Down syndrome critical region
      (DSCR)-1 gene in endothelial cells, a negative feedback regulator of calcineurin
      NFAT signaling. Constitutive expression of DSCR-1 in activated endothelial cells
      markedly impaired NFAT nuclear localization, proliferation, tube formation, and
      tumor growth. The goal of the present study was to elucidate the relative roles
      of NFAT/DSCR-1 and NF-kappaB/I-kappaB in mediating thrombin-responsive gene
      expression in endothelial cells. DNA microarrays of thrombin-treated human
      umbilical vein endothelial cells overexpressing DSCR-1 or constitutive active
      IkappaBalpha revealed genes that were dependent on NFAT and/or NF-kappaB
      activity. Vascular cell adhesion molecule-1 was inhibited both by DSCR-1 and I
      kappaB at the level of mRNA, protein, promoter activity, and function (monocyte
      adhesion). Using a combination of transient transfections, electrophoretic
      mobility shift assays, and chromatin immunoprecipitation, thrombin was shown to
      induce time-dependent coordinate binding of RelA and NFATc to a tandem NF-kappaB
      element in the upstream promoter region of vascular cell adhesion molecule-1.
      Together, these findings suggest that thrombin-mediated activation of endothelial
      cells involves an interplay between NFAT and NF-kappaB signaling pathways and
      their negative feedback inhibitors, DSCR-1 and I-kappaB, respectively. As natural
      brakes in the inflammatory process, DSCR-1 and I-kappaB may lend themselves to
      therapeutic manipulation in vasculopathic disease states.

PMID- 16627482
TI  - Kinetic mechanisms of the oxygenase from a two-component enzyme, p
      hydroxyphenylacetate 3-hydroxylase from Acinetobacter baumannii.
AB  - p-Hydroxyphenylacetate hydroxylase (HPAH) from Acinetobacter baumannii catalyzes
      the hydroxylation of p-hydroxyphenylacetate (HPA) to form 3,4
      dihydroxyphenylacetate (DHPA). The enzyme system is composed of two proteins: an
      FMN reductase (C1) and an oxygenase that uses FMNH- (C2). We report detailed
      transient kinetics studies at 4 degrees C of the reaction mechanism of C2.C2
      binds rapidly and tightly to reduced FMN (Kd, 1.2 +/- 0.2 microm), but less
      tightly to oxidized FMN (Kd, 250 +/- 50 microm). The complex of C -FMNH-2 reacted
      with oxygen to form C(4a)-hydroperoxy-FMN at 1.1 +/- 0.1 x 10(6) m(-1) s(-1),
      whereas the C -FMNH-2 -HPA complex reacted with oxygen to form C(4a)-hydroperoxy
      FMN-HPA more slowly (k = 4.8 +/- 0.2 x 10(4) m(-1) s(-1)). The kinetic mechanism
      of C2 was shown to be a preferential random order type, in which HPA or oxygen
      can initially bind to the C -FMNH-2 complex, but the preferred path was oxygen
      reacting with C -FMNH-2 to form the C(4a)-hydroperoxy-FMN intermediate prior to
      HPA binding. Hydroxylation occurs from the ternary complex with a rate constant
      of 20 s(-1) to form the C2-C(4a)-hydroxy-FMN-DHPA complex. At high HPA
      concentrations (>0.5 mm), HPA formed a dead end complex with the C2-C(4a)-hydroxy
      FMN intermediate (similar to single component flavoprotein hydroxylases), thus
      inhibiting the bound flavin from returning to the oxidized form. When FADH- was
      used, C(4a)-hydroperoxy-FAD, C(4a)-hydroxy-FAD, and product were formed at rates
      similar to those with FMNH-. Thus, C2 has the unusual ability to use both common
      flavin cofactors in catalysis.

PMID- 16627483
TI  - Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate
      dehydrogenase.
AB  - 10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes the NADP(+)-dependent
      conversion of 10-formyltetrahydrofolate to CO(2) and tetrahydrofolate (THF) and
      is an abundant high affinity folate-binding protein. Although several activities
      have been ascribed to FDH, its metabolic role in folate-mediated one-carbon
      metabolism is not well understood. FDH has been proposed to: 1) inhibit purine
      biosynthesis by depleting 10-formyl-THF pools, 2) maintain cellular folate
      concentrations by sequestering THF, 3) deplete the supply of folate-activated one
      carbon units, and 4) stimulate the generation of THF-activated one-carbon unit
      synthesis by channeling folate cofactors to other folate-dependent enzymes. The
      metabolic functions of FDH were investigated in neuroblastoma, which do not
      contain detectable levels of FDH. Both low and high FDH expression reduced total
      cellular folate concentrations by 60%, elevated rates of folate catabolism, and
      depleted cellular 5-methyl-THF and S-adenosylmethionine levels. Low FDH
      expression increased the formyl-THF/THF ratio nearly 10-fold, whereas THF
      accounted for nearly 50% of total folate in neuroblastoma with high FDH
      expression. FDH expression did not affect the enrichment of exogenous formate
      into methionine, serine, or purines and did not suppress de novo purine
      nucleotide biosynthesis. We conclude that low FDH expression facilitates the
      incorporation of one-carbon units into the one-carbon pool, whereas high levels
      of FDH expression deplete the folate-activated one-carbon pool by catalyzing the
      conversion of 10-formyl-THF to THF. Furthermore, FDH does not increase cellular
      folate concentrations by sequestering THF in neuroblastoma nor does it inhibit or
      regulate de novo purine biosynthesis. FDH expression does deplete cellular 5
      methyl-THF and S-adenosylmethionine levels indicating that FDH impairs the folate
      dependent homocysteine remethylation cycle.

PMID- 16627484
TI  - c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2
      synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1
      expression and prostaglandin E2 biosynthesis by cardiomyocytes.
AB  - Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes the terminal
      step in the biosynthesis of PGE(2), a key proinflammatory mediator. The purpose
      of this study was to elucidate the regulation of mPGES-1 mRNA expression in
      cardiomyocytes, define the role of JNK enzymes in this process, and characterize
      the role of mPGES-1 in cardiomyocyte PGE(2) biosynthesis. In neonatal
      cardiomyocytes, interleukin-1beta and lipopolysaccharide (LPS) both stimulated
      mPGES-1 mRNA expression and increased mPGES-1 mRNA stability and protein
      synthesis but failed to increase mPGES-1 mRNA transcription. Treatment with the
      JNK1/2 inhibitor, SP600125, abrogated the increases in mPGES-1 mRNA stability,
      mPGES-1 protein synthesis, and PGE(2) release induced by interleukin-1beta or
      LPS. mPGES-1 protein synthesis was observed in LPS-stimulated neonatal
      cardiomyocytes from jnk1(-/-) or jnk2(-/-) mice. In contrast, infection of jnk1(
      /-) cardiomyocytes with an adenovirus encoding phosphorylation-resistant JNK2 (ad
      JNK2-DN), or of jnk2(-/-) cardiomyocytes with ad-JNK1-DN, significantly decreased
      LPS-stimulated mPGES-1 protein synthesis. Similarly, co-infection with ad-JNK1-DN
      and ad-JNK2-DN attenuated LPS-stimulated mPGES-1 protein synthesis in
      cardiomyocytes from wild type mice. Targeted deletion of the gene encoding mPGES
      1 led to a 3.2-fold decrease in LPS-stimulated PGE(2) release by cardiomyocytes
      in comparison with wild type cells but had no effect on COX-1, COX-2, mPGES-2, or
      cytosolic PGES mRNA levels. These studies provide direct evidence that mPGES-1
      mRNA levels in cardiomyocytes are augmented by stabilization of mPGES-1 mRNA,
      that JNK1 or JNK2 can participate in the regulation of mPGES-1 protein synthesis
      in these cells, and that mPGES-1 catalyzes the majority of LPS-induced PGE(2)
      biosynthesis by cardiomyocytes.

PMID- 16627485
TI  - Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell
      motility of glioblastoma by converting lysophosphatidylcholine to
      lysophosphatidic acid.
AB  - Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from
      melanoma cells as a potent cell motility-stimulating factor. ATX is identical to
      lysophospholipase D, which produces a bioactive phospholipid, lysophosphatidic
      acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of
      ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is
      implicated in progression of tumor, the precise role of ATX expressed by tumor
      cells was unclear. In this study, we found that ATX is highly expressed in
      glioblastoma multiforme (GBM), the most malignant glioma due to its high
      infiltration into the normal brain parenchyma, but not in tissues from other
      brain tumors. In addition, LPA1, an LPA receptor responsible for LPA-driven cell
      motility, is predominantly expressed in GBM. One of the glioblastomas that showed
      the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed
      LPA1-dependent cell migration in response to LPA in both Boyden chamber and wound
      healing assays. Interestingly these ATX-expressing cells also showed chemotactic
      response to LPC. In addition, knockdown of the ATX level using small interfering
      RNA technique in SNB-78 cells suppressed their migratory response to LPC. These
      results suggest that the autocrine production of LPA by cancer cell-derived ATX
      and exogenously supplied LPC contribute to the invasiveness of cancer cells and
      that LPA1, ATX, and LPC-producing enzymes are potential targets for cancer
      therapy, including GBM.

PMID- 16627486
TI  - A common site of the Fc receptor gamma subunit interacts with the unrelated
      immunoreceptors FcalphaRI and FcepsilonRI.
AB  - The transmembrane (TM) region of the Fc receptor-gamma (FcRgamma) chain is
      responsible for the association of this ubiquitous signal transduction subunit
      with many immunoreceptor ligand binding chains, making FcRgamma key to a number
      of leukocyte activities in immunity and disease. Some receptors contain a TM
      arginine residue that interacts with Asp-11 of the FcRgamma subunit, but
      otherwise the molecular basis for the FcRgamma subunit interactions is largely
      unknown. This study reports residues in the TM region of the FcRgamma subunit are
      important for association with the high affinity IgE receptor FcepsilonRI and a
      leukocyte receptor cluster member, the IgA receptor FcalphaRI. FcRgamma residue
      Leu-21 was essential for surface expression of FcepsilonRIalpha/gamma2 and Tyr-8,
      Leu-14, and Phe-15 contributed to expression. Likewise, detergent-stable FcRgamma
      association with FcalphaRI was also dependent on Leu-14 and Leu-21 and in
      addition required residues Tyr-17, Tyr-25, and Cys-26. Modeling the TM regions of
      the FcRgamma dimer indicated these residues interacting with both FcalphaRI and
      FcepsilonRI are near the interface between the two FcRgamma TM helices.
      Furthermore, the FcRgamma residues interacting with FcalphaRI form a leucine
      zipper-like interface with mutagenesis confirming a complementary interface
      comprising FcalphaRI residues Leu-217, Leu-220, and Leu-224. The dependence of
      these two nonhomologous receptor interactions on FcRgamma Leu-14 and Leu-21
      suggests that all the associated Fc receptors and the activating leukocyte
      receptor cluster members interact with this one site. Taken together these data
      provide a molecular basis for understanding how disparate receptor families
      assemble with the FcRgamma subunit.

PMID- 16627487
TI  - Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community
      acquired pneumonia in Istanbul, Turkey.
AB  - BACKGROUND: To investigate the role of Mycoplasma pneumoniae and Chlamydia
      pneumoniae infection in pediatric pneumonia, in Istanbul, Turkey, we conducted a
      prospective study covering all the children between 2 months and 15 years
      hospitalized for community-acquired pneumonia. METHODS: A total of 140 children
      (85 males, median age 2.5 years) with community-acquired pneumonia were enrolled.
      Acute and convalescent sera were tested for IgM and IgG antibodies to M.
      pneumoniae (enzyme-linked immunosorbent assay, Serion ELISA classic) and for IgM
      and IgG antibodies to C. pneumoniae (microimmunofluorescence, Savyon, Israel).
      RESULTS: Mycoplasma pneumoniae infection was diagnosed in 38 patients (27%) and
      C. pneumoniae infection in 7 (5%). In 2 children M. pneumoniae and C. pneumoniae
      co infection was observed. The average age of the M. pneumoniae cases was 5.3
      years and that of the C. pneumoniae was 1.5 years. The average age of pneumonia
      cases caused by other pathogens was 3.4 years (p<0.05). No significant difference
      was observed in clinical onset, signs, symptoms and laboratory parameters in
      children with M. pneumoniae and C. pneumoniae infection and in those without M.
      pneumoniae and C. pneumoniae infection. CONCLUSIONS: The results of this study
      suggest a remarkable role for M. pneumoniae and C. pneumoniae in childhood
      community-acquired pneumonia, and the knowledge of the true prevalence of these
      two types of infections discovered in the community might lead to modifications
      in the present empirical treatment of bacterial pneumonia.

PMID- 16627488
TI  - Sample sizes of studies on diagnostic accuracy: literature survey.
AB  - OBJECTIVES: To determine sample sizes in studies on diagnostic accuracy and the
      proportion of studies that report calculations of sample size. DESIGN: Literature
      survey. DATA SOURCES: All issues of eight leading journals published in 2002.
      METHODS: Sample sizes, number of subgroup analyses, and how often studies
      reported calculations of sample size were extracted. RESULTS: 43 of 8999 articles
      were non-screening studies on diagnostic accuracy. The median sample size was 118
      (interquartile range 71-350) and the median prevalence of the target condition
      was 43% (27-61%). The median number of patients with the target condition--needed
      to calculate a test's sensitivity--was 49 (28-91). The median number of patients
      without the target condition--needed to determine a test's specificity--was 76
      (27-209). Two of the 43 studies (5%) reported a priori calculations of sample
      size. Twenty articles (47%) reported results for patient subgroups. The number of
      subgroups ranged from two to 19 (median four). No studies reported that sample
      size was calculated on the basis of preplanned analyses of subgroups. CONCLUSION:
      Few studies on diagnostic accuracy report considerations of sample size. The
      number of participants in most studies on diagnostic accuracy is probably too
      small to analyse variability of measures of accuracy across patient subgroups.

PMID- 16627489
TI  - Educational programmes for young people with eczema.

PMID- 16627490
TI  - Why should preterm births be rising?

PMID- 16627491
TI  - Are virtual communities good for our health?

PMID- 16627492
TI  - Court awards claimant 13.5m dollars in rofecoxib lawsuit.

PMID- 16627496
TI  - Dutch doctors suspended for use of complementary medicine.

PMID- 16627497
TI  - Johns Hopkins scales down its deal with cosmetics firm after criticism.

PMID- 16627505
TI  - Indian doctors debate increased affirmative action for lower castes.

PMID- 16627508
TI  - Tossed aside.

PMID- 16627509
TI  - Age related, structured educational programmes for the management of atopic
      dermatitis in children and adolescents: multicentre, randomised controlled trial.
AB  - OBJECTIVE: To determine the effects of age related, structured educational
      programmes on the management of moderate to severe atopic dermatitis in childhood
      and adolescence. DESIGN: Multicentre, randomised controlled trial. SETTING: Seven
      hospitals in Germany. PARTICIPANTS: Parents of children with atopic dermatitis
      aged 3 months to 7 years (n = 274) and 8-12 years (n = 102), adolescents with
      atopic dermatitis aged 13-18 years (n = 70), and controls (n = 244, n = 83, and n
      = 50, respectively). INTERVENTIONS: Group sessions of standardised intervention
      programmes for atopic dermatitis once weekly for six weeks or no education
      (control group). MAIN OUTCOME MEASURES: Severity of eczema (scoring of atopic
      dermatitis scale), subjective severity (standardised questionnaires), and quality
      of life for parents of affected children aged less than 13 years, over 12 months.
      RESULTS: Significant improvements in severity of eczema and subjective severity
      were seen in all intervention groups compared with control groups (total score
      for severity: age 3 months to 7 years - 17.5, 95% confidence intervals - 19.6 to 
      15.3 v - 12.2, - 14.3 to - 10.1; age 8-12 years - 16.0, - 20.0 to - 12.0 v -
      7.8, - 11.4; - 4.3; and age 13-18 years - 19.7, - 23.7 to - 15.7 v - 5.2, - 10.5
      to 0.1). Parents of affected children aged less than 7 years experienced
      significantly better improvement in all five quality of life subscales, whereas
      parents of affected children aged 8-12 years experienced significantly better
      improvement in three of five quality of life subscales. CONCLUSION: Age related
      educational programmes for the control of atopic dermatitis in children and
      adolescents are effective in the long term management of the disease.

PMID- 16627510
TI  - The double benefits of educational programmes for patients with eczema.

PMID- 16627511
TI  - Atorvastatin may cause nightmares.

PMID- 16627512
TI  - Panic disorder.

PMID- 16627513
TI  - From burns unit to boardroom.

PMID- 16627515
TI  - Syncope and falls due to timolol eye drops.

PMID- 16627516
TI  - Recent advances and emerging treatments.

PMID- 16627518
TI  - Importance of relative measures in policy on health inequalities.

PMID- 16627519
TI  - Reporting attrition in randomised controlled trials.

PMID- 16627520
TI  - Call for shake up in NHS funding: clarifications from Doctors for Reform.

PMID- 16627521
TI  - Call for shake up in NHS funding: few GPs among the 900 Doctors for Reform.

PMID- 16627522
TI  - Call for shake up in NHS funding: Nye Bevan's view on national and private
      insurance.

PMID- 16627523
TI  - Call for shake up in NHS funding: a reply to 900 doctors.

PMID- 16627524
TI  - Hypertension and ethnic group: eplerenone may have role in hypertension related
      atrial fibrillation.

PMID- 16627525
TI  - Hypertension and ethnic group: not as simple as black or white.

PMID- 16627526
TI  - Pay for efficiency, not simply more work.

PMID- 16627527
TI  - More on bird flu.

PMID- 16627528
TI  - Referral management centres: is this an April fool?

PMID- 16627529
TI  - Referral management centres: general practitioner colleagues could refer among
      themselves.

PMID- 16627530
TI  - Referral management centres: more Hackney carriage than Trojan horse.

PMID- 16627531
TI  - Competence in children has a Scottish twist.

PMID- 16627532
TI  - A sexist celebration.

PMID- 16627533
TI  - Blanket hepatitis B vaccination is questionable in India.

PMID- 16627534
TI  - Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in
      the UK.
AB  - Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt
      Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case
      of CJD in a porcine dura graft recipient. The mean incubation period of the human
      dura mater cases was 93 (range 45-177) months. The clinico-pathological features
      of the cases are described and compared with cases previously reported in the
      world literature.

PMID- 16627535
TI  - Severe cerebral congophilic angiopathy coincident with increased brain aluminium
      in a resident of Camelford, Cornwall, UK.
AB  - In July 1988, 20 tonnes of aluminium sulphate was discharged by the South West
      Water Authority into the drinking water supplied to a large region of North
      Cornwall. Up to 20,000 people were exposed to concentrations of aluminium which
      were 500-3000 times the acceptable limit under European Union legislation (0.200
      mg/l). Although this incident is currently the topic of a government inquiry,
      nothing is known about its longer-term repercussions on human health. The first
      neuropathological examination of a person who was exposed and died of an
      unspecified neurological condition was carried out. A rare form of sporadic early
      onset beta amyloid angiopathy in cerebral cortical and leptomeningeal vessels,
      and in leptomeningeal vessels over the cerebellum was identified. In addition,
      high concentrations of aluminium were found coincident with the severely affected
      regions of the cortex. Although the presence of aluminium is highly unlikely to
      be adventitious, determining its role in the observed neuropathology is
      impossible. A clearer understanding of aluminium's role in this rare form of
      Alzheimer's related disease should be provided by future research on other people
      from the exposed population as well as similar neuropathologies in people within
      or outside this group.

PMID- 16627536
TI  - Exposure to aluminium and the subsequent development of a disorder with features
      of Alzheimer's disease.

PMID- 16627537
TI  - Biphasic behaviour in malignant invasion.
AB  - Invasion is an important facet of malignant growth that enables tumour cells to
      colonise adjacent regions of normal tissue. Factors known to influence such
      invasion include the rate at which the tumour cells produce tissue-degrading
      molecules, or proteases, and the composition of the surrounding tissue matrix. A
      common feature of experimental studies is the biphasic dependence of the speed at
      which the tumour cells invade on properties such as protease production rates and
      the density of the normal tissue. For example, tumour cells may invade dense
      tissues at the same speed as they invade less dense tissue, with maximal invasion
      seen for intermediate tissue densities. In this paper, a theoretical model of
      malignant invasion is developed. The model consists of two coupled partial
      differential equations describing the behaviour of the tumour cells and the
      surrounding normal tissue. Numerical methods show that the model exhibits steady
      travelling wave solutions that are stable and may be smooth or discontinuous.
      Attention focuses on the more biologically relevant, discontinuous solutions
      which are characterised by a jump in the tumour cell concentration. The model
      also reproduces the biphasic dependence of the tumour cell invasion speed on the
      density of the surrounding normal tissue. We explain how this arises by seeking
      constant-form travelling wave solutions and applying non-standard phase plane
      methods to the resulting system of ordinary differential equations. In the phase
      plane, the system possesses a singular curve. Discontinuous solutions may be
      constructed by connecting trajectories that pass through particular points on the
      singular curve and recross it via a shock. For certain parameter values, there
      are two points at which trajectories may cross the singular curve and, as a
      result, two distinct discontinuous solutions may arise.

PMID- 16627538
TI  - Simultaneous constraints on pre- and post-synaptic cells couple cortical feature
      maps in a 2D geometric model of orientation preference.
AB  - The most prominent feature of mammalian striate cortex (V1) is the spatial
      organization of response preferences for the position and orientation of
      elementary visual stimuli. Models for the formation of cortical maps of
      orientation and 'retinotopic' position typically rely on a combination of Hebbian
      or correlation-based synaptic plasticity, and constraints on the distribution of
      synaptic weights. We consider a simplified model of orientation and retinotopic
      specificity based on the geometry of the feed-forward synaptic weight
      distribution from an 'unoriented' layer of cells to a first weakly oriented
      layer. We model the feed-forward weight distribution as a system of planar
      Gaussian receptive fields each elongated in the direction matching the preferred
      orientation of the postsynaptic cell. Under the constraint of presynaptic weight
      normalization (each cell in the oriented layer receives the same net synaptic
      weight) and a uniform retinotopic map (displacement of centres of mass of
      receptive fields in the unoriented layer is strictly proportional to the
      displacement of the corresponding cells in the oriented layer), we find that
      imposing a pattern of orientation preference forces the system to violate
      postsynaptic weight normalization (each cell in the unoriented layer no longer
      sends forth the same net synaptic weight). We study this deviation from
      uniformity of the postsynaptic weight, and find that the deviation has a distinct
      form in the vicinity of the 'pinwheel' singularities of the orientation map. We
      show that uniform synaptic coverage of the unoriented layer can be restored by
      introducing a distortion in the retinotopic locations of the receptive fields. We
      calculate, to first order in the relative elongation of the receptive fields, the
      retinotopic distortion vector field. Both the pattern of postsynaptic weight non
      uniformity and the corrective retinotopic distortion vector field fail to possess
      the reflection symmetry commonly assumed to relate orientation singularities with
      topological index +/- pi. Hence, we show that 'right-handed' and 'left-handed'
      orientation singularities are funda-mentally distinct anatomical structures when
      full 2D synaptic architecture is taken into account. Finally, we predict specific
      patterns of retinotopic distortion that should obtain in the vicinity of +/- pi
      fold orientation singularities, if uniform pre- and post-synaptic weight
      constraints are strongly enforced.

PMID- 16627539
TI  - Clinical classification criteria for knee osteoarthritis: performance in the
      general population and primary care.
AB  - BACKGROUND: Doubts have been expressed about the performance of the American
      College of Rheumatology (ACR) clinical classification criteria for osteoarthritis
      when applied in the general population. OBJECTIVE: To investigate whether the
      distribution of population subgroups and underlying disease severity might
      explain the performance of these criteria in the population setting. METHODS:
      Population-based cross-sectional study. 819 adults aged > or = 50 years reporting
      knee pain in the last 12 months were clinically assessed by research therapists
      using standardised protocols and blinded to radiographic status. All participants
      underwent plain radiography of the knees, scored by a single reader blinded to
      clinical status. The relationship between fulfilling the ACR clinical
      classification criteria for knee osteoarthritis and the presence of symptomatic
      radiographic knee osteoarthritis was summarised for the sample as a whole and
      within subgroups. RESULTS: Radiographic osteoarthritis was present in 539
      participants (68%) and symptomatic radiographic knee osteoarthritis in 259 (33%).
      238 participants (30%) fulfilled the ACR clinical criteria for knee
      osteoarthritis. Agreement between the ACR clinical criteria and symptomatic
      radiographic knee osteoarthritis was low (sensitivity 41%; specificity 75%;
      positive predictive value 44%; negative predictive value 72%). Sensitivity and
      specificity did not vary markedly between population subgroups, although they
      were influenced by the underlying severity of radiographic osteoarthritis.
      CONCLUSION: The ACR clinical criteria seem to reflect later signs in advanced
      disease. Other approaches may be needed to identify early, mild osteoarthritis in
      the general population and primary care.

PMID- 16627540
TI  - Combined high-resolution magnetic resonance imaging and histological examination
      to explore the role of ligaments and tendons in the phenotypic expression of
      early hand osteoarthritis.
AB  - BACKGROUND: The pathogenesis of the early stages of hand osteoarthritis is poorly
      understood, but recent high-resolution magnetic resonance imaging (hrMRI) studies
      suggest that the joint ligaments have a major role in the phenotypic expression
      of the disease. OBJECTIVE: To combine hrMRI and cadaveric histological studies to
      better understand the mechanisms of damage, and especially the role of joint
      ligaments and tendons in disease expression. METHODS: hrMRI was carried out in
      the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in 20
      patients with osteoarthritis, with a disease duration < or = 12 months.
      Histological sections of the DIP and PIP joints were obtained from three
      dissecting-room specimens for comparative analysis. RESULTS: The collateral
      ligaments influenced the location of both hrMRI-determined bone oedema and bone
      erosion in early osteoarthritis. These changes were best understood in relation
      to the enthesis organ concept, whereby the interaction between ligament
      fibrocartilages leads to bone disease. Normal ligaments were commonly associated
      with microdamage at insertions corresponding to ligament thickening noted in
      early osteoarthritis. The ligaments also influenced the location of node
      formation in early osteoarthritis. The DIP extensor tendon insertions were
      associated with the development of a neoarticular surface. CONCLUSIONS: Small
      joint collateral ligaments and tendons have a central role in the early stages of
      hand osteoarthritis, and determine the early expression of both the soft tissue
      and bony changes in disease.

PMID- 16627541
TI  - Childhood onset arthritis is associated with an increased risk of fracture: a
      population based study using the General Practice Research Database.
AB  - BACKGROUND: Childhood onset arthritis is associated with low bone mass and
      strength. OBJECTIVE: To determine whether childhood onset arthritis is associated
      with greater fracture risk. METHODS: In a retrospective cohort study all subjects
      with onset of arthritis between 1 and 19 years of age in the United Kingdom
      General Practice Research Database were identified. As controls, all sex and age
      matched subjects from a practice that included a subject with arthritis were
      included. Incidence rate ratios (IRRs) for first fracture were generated using
      Mantel-Haenszel methods and Poisson regression. RESULTS: 1939 subjects with
      arthritis (51% female) and 207 072 controls (53% female) were identified. The
      median age at arthritis diagnosis was 10.9 years. A total of 129 (6.7%) first
      fractures were noted in subjects with arthritis compared with 6910 (3.3%) in
      controls over a median follow up of 3.90 and 3.95 years in the subjects with
      arthritis and controls, respectively. The IRR (95% confidence interval) for first
      fracture among subjects with arthritis, compared with controls, according to the
      age at the start of follow up were 1.49 (0.91 to 2.31) for age <10 years, 3.13
      (2.21 to 4.33) at 10-15 years, 1.75 (1.18 to 2.51) at 15-20 years, 1.40 (0.91 to
      2.08) at 20-45 years, and 3.97 (2.23 to 6.59) at >45 years. CONCLUSIONS:
      Childhood onset arthritis is associated with a clinically significant increased
      risk of fracture in children, adolescents and, possibly, adults. Studies are
      urgently needed to characterise the determinants of structural bone abnormalities
      in childhood arthritis and devise prevention and treatment strategies.

PMID- 16627542
TI  - Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic
      diseases: assessment and preventive strategies.
AB  - Understanding of the natural history and basic biology of hepatitis B virus (HBV)
      has increased greatly in recent years. In view of this, the following are
      reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic
      disease population; (b) the risks of HBV reactivation in patients with rheumatic
      disease undergoing immunosuppression; and (c) potential strategies to manage
      these risks.

PMID- 16627543
TI  - Pretreatment macrophage infiltration of the synovium predicts the clinical effect
      of both radiation synovectomy and intra-articular glucocorticoids.
AB  - OBJECTIVE: To explore whether pretreatment features of synovial tissue in
      patients with gonarthritis could predict the clinical effect of radiation
      synovectomy with yttrium-90 (90Y) and glucocorticoids or with intra-articular
      glucocorticoids alone. METHODS: A synovial biopsy was carried out blindly 2 weeks
      before treatment in 66 patients with persistent gonarthritis, who were randomised
      to treatment either with 90Y and triamcinolone or with placebo and triamcinolone.
      Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma
      cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory
      cytokines. Stained sections were evaluated by digital image analysis. Individual
      patient improvement was expressed using a composite change index (CCI; range 0
      12). Successful treatment was defined as CCI > or = 6 after 6 months. RESULTS:
      Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated
      arthritis and other causes of gonarthritis were included. The overall response
      rate was 47%. Clinical efficacy in both therapeutic groups was similar and not
      dependent on diagnosis. No significant differences were noted between baseline
      microscopic features of synovial tissue inflammation in patients with rheumatoid
      arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other
      than rheumatoid arthritis). The number of macrophages in the synovial sublining
      was significantly higher in responders than in non-responders (p = 0.002),
      independent of treatment group and diagnosis. The clinical effect was positively
      correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03),
      sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion
      molecule 1 expression (r = 0.25; p = 0.04). CONCLUSION: The observations support
      the view that intra-articular treatment either with 90Y and glucocorticoids or
      with glucocorticoids alone is especially successful in patients with marked
      synovial inflammation.

PMID- 16627544
TI  - Ethnicity and mortality from systemic lupus erythematosus in the US.
AB  - OBJECTIVE: To study ethnic differences in mortality from systemic lupus
      erythematosus (lupus) in two large, population-based datasets. METHODS: We
      analysed the national death data (1979-98) from the National Center for Health
      Statistics (Hyattsville, Maryland, USA) and hospitalisation data (1993-2002) from
      the Nationwide Inpatient Sample (NIS), the largest hospitalisation database in
      the US. RESULTS: The overall, unadjusted, lupus mortality in the National Center
      for Health Statistics data was 4.6 per million, whereas the proportion of in
      hospital mortality from the NIS was 2.9%. African-Americans had
      disproportionately higher mortality risk than Caucasians (all-cause mortality
      relative risk adjusted for age = 1.24 (women), 1.36 (men); lupus mortality
      relative risk = 3.91 (women), 2.40 (men)). Excess risk was found among in
      hospital deaths (odds ratio adjusted for age = 1.4 (women), 1.3 (men)). Lupus
      death rates increased overall from 1979 to 98 (p<0.001). The proportional
      increase was greatest among African-Americans. Among Caucasian men, death rates
      declined significantly (p<0.001), but rates did not change substantially for
      African-American men. The African-American:Caucasian mortality ratio rose with
      time among men, but there was little change among women. In analyses of the NIS
      data adjusted for age, the in-hospital mortality risk decreased with time among
      Caucasian women (p<0.001). CONCLUSIONS: African-Americans with lupus have 2-3
      fold higher lupus mortality risk than Caucasians. The magnitude of the risk
      disparity is disproportionately higher than the disparity in all-cause mortality.
      A lupus-specific biological factor, as opposed to socioeconomic and access-to
      care factors, may be responsible for this phenomenon.

PMID- 16627545
TI  - Risk perception and attitudes towards HIV in Serbian health care workers.
AB  - BACKGROUND: Health care workers (HCWs) are at risk of occupational exposure to
      human immunodeficiency virus (HIV). AIM: To investigate the perception of
      professional risk from, and the knowledge, attitudes and practice of HCWs to HIV
      and AIDS in Serbia. METHODS: Cross-sectional study of 1,559 Serbian HCWs using
      self-administered anonymous questionnaires. Chi-square testing and multiple
      logistic regression analysis were applied. RESULTS: Eighty-nine per cent of HCWs
      believed that they were at risk of acquiring HIV through occupational exposure.
      The perception of professional risk was higher among HCWs frequently exposed to
      patients' blood and body fluids (OR 7.9, 95% CI 4.4-14.5), who used additional
      personal protection if the HIV status of patient was known (OR 2.6, 95% CI 1.5
      4.6), who had experienced sharp injuries within the last year (OR 1.9, 95% CI 1.0
      3.8) or who had been tested for HIV (OR 2.1, 95% CI 1.2-3.5), and among HCWs who
      had treated HIV-positive patients (OR 1.7, 95% CI 1.1-2.8). The majority of
      respondents had deficient knowledge about modes of HIV transmission. Attitudes
      towards HIV-positive patients were significantly different by occupation. Seventy
      per cent of HCWs used appropriate protection during their daily work with
      patients. CONCLUSIONS: HCWs require specific educational programmes and training
      protocols to ensure that they are adequately protected when carrying out high
      quality care.

PMID- 16627546
TI  - A descriptive study of workers' compensation claims in Washington State orchards.
AB  - BACKGROUND: Previous studies have reported high rates of occupational injury and
      illness among workers in the tree fruit industry. However, many common and
      preventable risk factors and conditions in orchards have not been investigated.
      AIMS: To identify and rank risk conditions leading to workers' compensation
      claims among orchard workers with respect to frequency, severity and cost.
      METHODS: State Fund workers' compensation claims between 1996 and 2001 for
      orchard workers in the main tree fruit growing region of Washington were reviewed
      and categorized according to cause of injury. Descriptive analyses were performed
      to characterize claims by cause of injury. RESULTS: Of the 13,068 claims in the
      dataset, 4,020 (31%) were determined to be ladder-related injuries. Ladder
      related claims accounted for nearly half (48%) of all 'compensable' claims (e.g.
      claims involving time loss, disability or 'loss of earning power' in addition to
      medical expenses). Claims related to ladders were not only the most frequent but
      also the most expensive collectively in terms of medical aid, time loss and other
      costs. On a per-claim basis, ladder-related injuries were among the most severe
      and costly reported injuries. Other common causes of injury among claims were
      branches and vegetation, structure and material and ground-related injuries.
      CONCLUSIONS: There is a strong and compelling need to develop interventions to
      reduce the number of ladder-related injuries in orchards.

PMID- 16627547
TI  - Risk factors for specific upper limb disorders as compared with non-specific
      upper limb pain: assessing the utility of a structured examination schedule.
AB  - BACKGROUND: Few community-based epidemiological investigations of upper limb
      disorders (ULDs) have classified cases by validated procedures involving a
      structured clinical examination. AIM: To compare risk factor profiles for
      different diagnostic categories of ULD using one such examination scheme.
      METHODS: A questionnaire about upper limb pain and demographic, occupational and
      psychosocial risk factors was mailed to 10,264 adults from two English general
      practices, followed by standardized physical examination in those with arm or
      neck pain. Logistic regression was used to compare those with specific ULDs and
      non-specific arm pain with those who had no neck or arm symptoms. RESULTS: There
      was a 59% response rate. A total of 1,197 subjects with arm or neck pain
      underwent standardized physical examination and were classified as having one or
      more of 11 specific ULDs or non-specific regional pain. Among these, 250 subjects
      with specific ULDs and 176 with only non-specific arm pain were compared with
      2,248 subjects who had no neck or arm symptoms. Certain physical risk factors
      were more strongly associated with specific disorders than with non-specific
      pain. In comparison with pain-free subjects, the odds ratios (ORs) in keyboard
      users (>or=1 h versus <1 h/day) were 3.1 (95% CI 1.3, 7.8) for hand-wrist
      tendonitis but 1.3 (0.8, 2.1) for non-specific hand-wrist pain. Other
      differential associations were found with age, sex, manual versus non-manual
      employment and smoking. Unexpectedly, low vitality was similarly associated with
      both specific disorders and non-specific pain. CONCLUSION: These findings suggest
      that the schedule may usefully distinguish disorders that differ in their
      association with physical risk factors.

PMID- 16627548
TI  - Treatment of non-cardiac chest pain: a controlled trial of hypnotherapy.
AB  - BACKGROUND: Non-cardiac chest pain (NCCP) is an extremely debilitating condition
      of uncertain origin which is difficult to treat and consequently has a high
      psychological morbidity. Hypnotherapy has been shown to be effective in related
      conditions such as irritable bowel syndrome where its beneficial effects are long
      lasting. AIMS: This study aimed to assess the efficacy of hypnotherapy in a
      selected group of patients with angina-like chest pain in whom coronary
      angiography was normal and oesophageal reflux was not contributory. PATIENTS AND
      METHODS: Twenty eight patients fulfilling the entry criteria were randomised to
      receive, after a four week baseline period, either 12 sessions of hypnotherapy or
      supportive therapy plus placebo medication over a 17 week period. The primary
      outcome measure was global assessment of chest pain improvement. Secondary
      variables were a change in scores for quality of life, pain severity, pain
      frequency, anxiety, and depression, as well as any alteration in the use of
      medication. RESULTS: Twelve of 15 (80%) hypnotherapy patients compared with three
      of 13 (23%) controls experienced a global improvement in pain (p = 0.008) which
      was associated with a significantly greater reduction in pain intensity (p =
      0.046) although not frequency. Hypnotherapy also resulted in a significantly
      greater improvement in overall well being in addition to a reduction in
      medication usage. There were no differences favouring hypnotherapy with respect
      to anxiety or depression scores. CONCLUSION: Hypnotherapy appears to have use in
      this highly selected group of NCCP patients and warrants further assessment in
      the broader context of this disorder.

PMID- 16627549
TI  - Problems of opioid availability and accessibility across Europe: ESMO tackles the
      regulatory causes of intolerable and needless suffering.

PMID- 16627550
TI  - Expression of chemokine receptors predicts the site of metastatic relapse in
      patients with axillary node positive primary breast cancer.
AB  - BACKGROUND: Recent studies have suggested that chemokine receptors are involved
      in development of organ-specific pattern of metastases. In the present study, we
      evaluated the association between the chemokine receptors expressed in primary
      tumor cells and the site of metastatic relapse in patients with breast cancer.
      METHODS: Primary tumors were obtained from 142 patients with axillary node
      positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression.
      All statistical analyses were adjusted for systemic post-operative treatment.
      RESULTS: After a median follow-up of 13 years, none of the chemokine receptors
      was associated with overall survival or disease free survival. However,
      expression of chemokine receptors was found to be associated with increased risk
      of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR),
      CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P
      = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P =
      0.01). Patients with CCR6 positivity were more likely to develop a first
      metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was
      associated with the occurrence of skin metastases (11% versus 0%, P = 0.017).
      INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts
      the site of metastatic relapse in patients with axillary node positive breast
      cancer. This study, in concordance with the data obtained in animal models,
      suggests that the chemokine receptors family could be the biological support of
      the 'seed and soil' theory.

PMID- 16627551
TI  - Promotion of neurogenesis by human stem cells in high-risk breast cancer
      survivals after stem-cell supported high-dose therapy.

PMID- 16627554
TI  - Intensive treatment of risk factors in patients with type-2 diabetes mellitus is
      associated with improvement of endothelial function coupled with a reduction in
      the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of
      nitric oxide synthase.
AB  - AIMS: Vascular endothelium is a major organ involved in hyperglycaemia and is
      affected by plasma asymmetric dimethylarginine (ADMA). ADMA is an endogenous,
      competitive inhibitor of nitric oxide synthase and is induced by inflammatory
      cytokines of tumour necrosis factor (TNF)-alpha in vitro. We hypothesized that a
      tight glycaemic control may restore endothelial function in patients with type-2
      diabetes mellitus (DM), in association with modulation of TNF-alpha and/or
      reduction of ADMA level. METHODS AND RESULTS: In 24 patients with type-2 DM, the
      flow-mediated, endothelium-dependent dilation (FMD: %) of brachial arteries
      during reactive hyperaemia was determined by a high-resolution ultrasound method.
      Blood samples for glucose, cholesterol, TNF-alpha, and ADMA analyses were also
      collected from these patients after fasting. No significant glycaemic or FMD
      changes were observed in 10 patients receiving the conventional therapy. In 14
      patients who were hospitalized and intensively treated, there was a significant
      decrease in glucose level after the treatment [from 190+/-55 to 117+/-21 (mean+/
      SD) mg/dL, P<0.01]. After the intensive control of glucose level, FMD increased
      significantly (from 2.5+/-0.9 to 7.2+/-3.0%), accompanied by a significant
      (P<0.01) decrease in TNF-alpha (from 29+/-16 to 11+/-9 pg/dL) and ADMA (from
      4.8+/-1.5 to 3.5+/-1.1 microM/L) levels. The changes in FMD after treatment
      correlated inversely with those in TNF-alpha (R=-0.711, P<0.01) and ADMA (R=
      0.717, P<0.01) levels. CONCLUSION: The intensive correction of hyperglycaemia is
      associated with the improvement of endothelial function, which is coupled with
      the decrease in the levels of reduction of plasma TNF-alpha and ADMA in patients
      with type-2 DM. A strict glycaemic control may exert anti-cytokine and anti
      atherogenic effects and may therefore be pathophysiologically important.

PMID- 16627555
TI  - In vitro and in vivo analysis of the thyroid system-disrupting activities of
      brominated phenolic and phenol compounds in Xenopus laevis.
AB  - We investigated the effects of the brominated phenolic and phenol compounds, some
      of which are brominated flame retardants, on the binding of (125)I-3,3',5-L
      triiodothyronine ((125)I-T(3)) to purified Xenopus laevis transthyretin (xTTR)
      and to the ligand-binding domain of X. laevis thyroid hormone receptor beta (xTR
      LBD), on the induction of a T(3)-responsive reporter gene in a recombinant X.
      laevis cell line (XL58-TRE-Luc) and on T(3)-induced or spontaneous metamorphosis
      in X. laevis tadpoles. Of the brominated phenolic and phenol compounds tested,
      3,3',5-tribromobisphenol A and 3,3'-dibromobisphenol A were the most potent
      competitors of (125)I-T(3) binding to xTTR and the xTR LBD, respectively.
      Structures with a bromine in either ortho positions with respect to the hydroxy
      group competed more efficiently with T(3) binding to xTTR and the xTR LBD. 3,3',5
      Tribromobisphenol A and 3,3',5,5'-tetrabromobisphenol A, at 0.1-1.0 microM,
      exerted both T(3) agonist and antagonist activities in the T(3)-responsive
      reporter gene assay. Sera obtained from fetal bovine and bullfrog tadpoles
      weakened the T(3) agonist and antagonist activities of 3,3',5-tribromobisphenol
      A, but not the T(3) antagonist activity of o-t-butylphenol, for which xTTR has no
      significant affinity. The T(3) agonist and antagonist activities of 0.5 microM
      3,3',5-tribromobisphenol A were confirmed in the in vivo, short-term gene
      expression assay in premetamorphic X. laevis tadpoles using endogenous, T(3)
      responsive genes as molecular markers. Our results suggest that 3,3',5
      tribromobisphenol A affects T(3) binding to xTTR and xTR and that it interferes
      with the intracellular T(3) signaling pathway.

PMID- 16627556
TI  - Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.
AB  - Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene
      defects have been detected, explaining the mechanism and diversity of iron
      overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have
      been identified. Surprisingly, genes involved in HH encode for proteins that all
      affect pathways centered around liver hepcidin synthesis and its interaction with
      ferroportin, an iron exporter in enterocytes and macrophages. Hepcidin
      concentrations in urine negatively correlate with the severity of HH. Cytokine
      mediated increases in hepcidin appear to be an important causative factor in
      anemia of inflammation, which is characterized by sequestration of iron in the
      macrophage system. For clinicians, the challenge is now to diagnose HH before
      irreversible damage develops and, at the same time, to distinguish progressive
      iron overload from increasingly common diseases with only moderately increased
      body iron stores, such as the metabolic syndrome. Understanding the molecular
      regulation of iron homeostasis may be helpful in designing innovative and
      reliable DNA and protein tests for diagnosis. Subsequently, evidence-based
      diagnostic strategies must be developed, using both conventional and innovative
      laboratory tests, to differentiate between the various causes of distortions of
      iron metabolism. This review describes new insights in mechanisms of iron
      overload, which are needed to understand new developments in diagnostic medicine.

PMID- 16627557
TI  - Analysis of sequence variations in the LDL receptor gene in Spain: general gene
      screening or search for specific alterations?
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a frequent form of autosomal
      dominant hypercholesterolemia that predisposes to premature coronary
      atherosclerosis. FH is caused by sequence variations in the gene coding for the
      LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and
      genetic diagnosis can be performed by 2 strategies. METHODS: Point variations and
      large rearrangements were screened along all the LDLR gene (promoter, exons, and
      flanking intron sequences). RESULTS: We screened a sample of 129 FH probands from
      the Valencian Community, Spain, and identified 54 different LDLR sequence
      variations. The most frequent (10% of cases) was 111insA, and 60% of the variants
      had a frequency as low as 1%. A previously described method for detection of
      known sequence variations in the Spanish population by DNA array analysis allowed
      the identification of only approximately 50% of patients with a variant LDLR gene
      and approximately 40% of the screened samples. CONCLUSION: Our results indicate
      that the adequate procedure to identify LDLR sequence variations in outbreed
      populations should include screening of the entire gene.

PMID- 16627558
TI  - Ultrasensitive monitoring of HIV-1 viral load by a low-cost real-time reverse
      transcription-PCR assay with internal control for the 5' long terminal repeat
      domain.
AB  - BACKGROUND: Current HIV-1 viral-load assays are too expensive for resource
      limited settings. In some countries, monitoring of antiretroviral therapy is now
      more expensive than treatment itself. In addition, some commercial assays have
      shown shortcomings in quantifying rare genotypes. METHODS: We evaluated real-time
      reverse transcription-PCR with internal control targeting the conserved long
      terminal repeat (LTR) domain of HIV-1 on reference panels and patient samples
      from Brazil (n = 1186), South Africa (n = 130), India (n = 44), and Germany (n =
      127). RESULTS: The detection limit was 31.9 IU of HIV-1 RNA/mL of plasma (> 95%
      probability of detection, Probit analysis). The internal control showed
      inhibition in 3.7% of samples (95% confidence interval, 2.32%-5.9%; n = 454; 40
      different runs). Comparative qualitative testing yielded the following: Roche
      Amplicor vs LTR assay (n = 431 samples), 51.7% vs 65% positives; Amplicor
      Ultrasensitive vs LTR (n = 133), 81.2% vs 82.7%; BioMerieux NucliSens HIV-1 QT (n
      = 453), 60.5% vs 65.1%; Bayer Versant 3.0 (n = 433), 57.7% vs 55.4%; total (n =
      1450), 59.0% vs 63.8% positives. Intra-/interassay variability at medium and near
      negative concentrations was 18%-51%. The quantification range was 50-10,000,000
      IU/mL. Viral loads for subtypes A-D, F-J, AE, and AG yielded mean differences of
      0.31 log(10) compared with Amplicor in the 10(3)-10(4) IU/mL range. HIV-1 N and O
      were not detected by Amplicor, but yielded up to 180 180.00 IU/mL in the LTR
      assay. Viral loads in stored samples from all countries, compared with Amplicor,
      NucliSens, or Versant, yielded regression line slopes (SD) of 0.9 (0.13) (P <
      0.001 for all). CONCLUSIONS: This method offers all features of commercial assays
      and covers all relevant genotypes. It could allow general monitoring of
      antiretroviral therapy in resource-limited settings.

PMID- 16627559
TI  - Quantitative reverse transcription-PCR assay for detection of mRNA encoding full
      length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in
      breast cancer.
AB  - BACKGROUND: The human tissue kallikrein gene family (KLK1 to KLK15) encodes a
      group of 15 serine proteases (hK1 to hK15), several of which have been implicated
      in cancer-related processes. METHODS: We established a specific quantitative
      reverse transcription-PCR assay for full-length KLK7 mRNA that excluded
      amplification of the exon 2 deletion splice variant (the latter does not encode a
      functional protease), and evaluated full-length KLK7 mRNA expression [normalized
      to human glucose-6-phosphate dehydrogenase (h-G6PDH)] in tumor tissue specimens
      from 155 breast cancer patients. RESULTS: High KLK7 mRNA expression (continuous)
      was significantly associated with a better patient outcome according to both
      univariate (P = 0.005) and multivariate (P = 0.046) Cox survival analysis.
      Separation of patients by optimized dichotomization revealed a significantly
      better prognosis for patients with high KLK7 mRNA status (n = 89) compared with
      patients with low KLK7 mRNA status (n = 66) [univariate hazard ratio (HR) = 0.45
      (P = 0.001); multivariate HR = 0.50 (P = 0.005)]. In the subgroup of patients not
      receiving adjuvant treatment (n = 69), KLK7 mRNA status was a significant
      prognosticator [univariate HR = 0.29 (P = 0.002); multivariate HR = 0.40 (P =
      0.034)]. This subgroup was least influenced by postoperative treatment and thus
      best showed the impact of KLK7 expression on the natural course of breast cancer
      disease. CONCLUSION: Expression of full-length KLK7 mRNA may represent a new
      prognostic marker in breast cancer disease.

PMID- 16627560
TI  - Immunoluminometric assay for measurement of the C-terminal endothelin-1 precursor
      fragment in human plasma.
AB  - BACKGROUND: Endothelin-1 (ET-1), a potent vasoconstrictor, is difficult to
      measure because of its instability and its binding to receptors and plasma
      proteins. We report a rapid, robust way to indirectly quantify ET-1 release by
      measuring the C-terminal ET-1 precursor fragment (CT-proET-1) without an
      extraction step. METHODS: In plasma samples from healthy individuals, patients
      with congestive heart failure (CHF), and patients with sepsis, we measured CT
      proET-1 with a sandwich immunoluminometric assay that uses 2 polyclonal
      antibodies to amino acids 168-212 of pre-proET-1. We also correlated CT-proET-1
      concentrations with bigET-1 measurements. RESULTS: The assay yielded results
      within 3 h and showed linear dilution with an analytical detection limit of 0.4
      pmol/L and an interlaboratory CV <10% for values >10 pmol/L. Ex vivo CT-proET-1
      was stable (<10% loss of immunoreactivity) in EDTA-, heparin-, and citrate-plasma
      for at least 4 h at room temperature, 6 h at 4 degrees C, and in EDTA-plasma for
      at least 6 months at -20 degrees C. CT-proET-1 values followed a gaussian
      distribution in healthy individuals (mean, 44.3 pmol/L; range, 10.5-77.4 pmol/L)
      without significant differences between males and females. The correlation
      coefficient for CT-proET-1 vs age was 0.25 (P <0.0001). CT-proET1 was
      significantly (P <0.0001) increased in patients with CHF (median, 104 pmol/L;
      range, 50.8-315 pmol/L) and patients with sepsis (median, 189 pmol/L; range, 34.6
      855 pmol/L). The correlation between CT-proET-1 and bigET-1 for 43 samples was
      0.80 (P <0.0001). CONCLUSIONS: CT-proET-1 measurement is a rapid and easy method
      for indirectly assessing the release of ET-1 in critically ill patients.

PMID- 16627561
TI  - APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis
      of prostate cancer.
AB  - BACKGROUND: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that
      has shown promise as a prostate cancer diagnostic tool. This report describes the
      characterization of a prototype quantitative PCA3-based test for whole urine.
      METHODS: Whole-urine specimens were collected after digital rectal examination
      from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years
      of age with no known prostate cancer risk factors; n = 52), and men who had
      undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen
      (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400
      Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio,
      and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the
      yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA
      yield were also evaluated. RESULTS: The specimen informative rate (fraction of
      specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical
      research study, ROC curve analysis of prebiopsy specimens yielded an area under
      the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay
      specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in
      postprostatectomy specimens except for one man with recurrent prostate cancer.
      Assay interrun CVs were < or =12%. Both mRNAs were stable in processed urine up
      to 5 days at 4 degrees C and after 5 freeze-thaw cycles. CONCLUSION: The APTIMA
      PCA3 assay combines simple specimen processing with precise assays and existing
      instruments and could add specificity to the current algorithm for prostate
      cancer diagnosis.

PMID- 16627562
TI  - Systematic comparison of the T7-IVT and SMART-based RNA preamplification
      techniques for DNA microarray experiments.
AB  - BACKGROUND: Small biological samples obtained from biopsies or laser
      microdissection often do not yield sufficient RNA for successful microarray
      hybridization; therefore, RNA amplification is performed before microarray
      experiments. We compared 2 commonly used techniques for RNA amplification.
      METHODS: We compared 2 commercially available methods, Arcturus RiboAmp for in
      vitro transcription (IVT) and Clontech BD SMART for PCR, to preamplify 50 ng of
      total RNA isolated from mouse livers and kidneys. Amplification factors of 3
      sequences were determined by real-time PCR. Differential expression profiles were
      compared within and between techniques as well as with unamplified samples with
      10K 50mer oligomer-spotted microarrays (MWG Biotech). The microarray results were
      validated on the transcript and protein levels by comparison with public
      expression databases. RESULTS: Amplification factors for specific sequences were
      lower after 2 rounds of IVT than after 12 cycles of SMART. Furthermore, IVT
      showed a clear decrease in amplification with increasing distance of the
      amplified sequences from the polyA tail, indicating generation of smaller
      products. In the microarray experiments, reproducibility of the duplicates was
      highest after SMART. In addition, SMART-processed samples showed higher
      correlation when compared with unamplified samples as well as with expression
      databases. CONCLUSIONS: Whenever 1 round of T7-IVT does not yield sufficient
      product for microarray hybridization, which is usually the case when <200 ng of
      total RNA is used as starting material, we suggest the use of SMART PCR for
      preamplification.

PMID- 16627563
TI  - The SK channel blocker apamin inhibits slow afterhyperpolarization currents in
      rat gonadotropin-releasing hormone neurones.
AB  - Gonadotropin-releasing hormone (GnRH) neurones play an essential role in the
      hypothalamo-pituitary-gonadal axis. As for other neurones, the discharge pattern
      of action potentials is important for GnRH neurones to properly function. In the
      case of a luteinizing hormone (LH) surge, for example, GnRH neurones are likely
      to continuously fire for more than an hour. For this type of firing, GnRH
      neurones must have a certain intrinsic property. To address this issue, we
      investigated the voltage-gated Ca(2+) currents and Ca(2+)-activated voltage
      independent K(+) currents underlying afterhyperpolarization, because they affect
      cell excitability. Dispersed GnRH neurones from adult GnRH-EGFP (enhanced green
      fluorescent protein) transgenic rats were cultured overnight and then used for an
      electrophysiological experiment involving the perforated patch-clamp
      configuration. The GnRH neurones showed five subtypes of voltage-gated Ca(2+)
      currents, i.e. the T-, L-, N-, P/Q- and R-types. The GnRH neurones also showed a
      slow afterhyperpolarization current (I(sAHP)), but not a medium one. It is
      reported that the SK channel blocker apamin (10 pm-100 nm) blocks a medium
      afterhyperpolarization current but not an I(sAHP). In contrast to previous
      reports, the I(sAHP) observed in rat GnRH neurones was potently blocked by
      apamin. In addition, the GnRH neurones expressed transcripts for SK1-3 channels.
      The results indicate that rat GnRH neurones express all five subtypes of voltage
      gated Ca(2+) channels and exhibit an apamin-sensitive I(sAHP), which may allow
      continuous firing in response to a relatively strong depolarizing input.

PMID- 16627564
TI  - The importance of occupancy rather than affinity of CaV(beta) subunits for the
      calcium channel I-II linker in relation to calcium channel function.
AB  - The Ca(V)beta subunits of voltage-gated calcium channels regulate the trafficking
      and biophysical properties of these channels. We have taken advantage of
      mutations in the tyrosine residue within the alpha interaction domain (AID) in
      the I-II linker of Ca(V)2.2 which reduce, but do not abolish, the binding of
      beta1b to the AID of Ca(V)2.2. We have found that the mutation Y388S decreased
      the affinity of Ca(V)beta1b binding to the Ca(V)2.2 I-II linker from 14 to 329
      nm. However, the Y388S mutation had no effect on current density and cell surface
      expression of Ca(V)2.2/alpha2delta-2/beta1b channels expressed in human embryonic
      kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore,
      despite the 24-fold reduced affinity of Ca(V)beta1b for the Y388S I-II linker of
      Ca(V)2.2, all the key features of modulation as well as trafficking by Ca(V)beta
      subunits remained intact. This is in contrast to the much more marked effect of
      the W391A mutation, which abolished interaction with the Ca(V)2.2 I-II linker,
      and very markedly affected the trafficking of the channels. However, using the
      Xenopus oocyte expression system, where expression levels can be accurately
      titrated, when Ca(V)beta1b cDNA was diluted 50-fold, all evidence of interaction
      with Ca(V)2.2 Y388S was lost, although wild-type Ca(V)2.2 was still normally
      modulated by the reduced concentration of beta1b. These results indicate that
      high affinity interaction with the alpha1 subunit is not necessary for any of the
      modulatory effects of Ca(V)beta subunits, but occupancy of the interaction site
      is important, and this will occur, despite the reduced affinity, if the Ca(V)beta
      subunit is present in sufficient excess.

PMID- 16627565
TI  - Calmodulin kinase II accelerates L-type Ca2+ current recovery from inactivation
      and compensates for the direct inhibitory effect of [Ca2+]i in rat ventricular
      myocytes.
AB  - Some studies report that the positive relationship between L-type Ca(2+) current
      (I(Ca-L)) and frequency in cardiac myocytes is mainly due to a direct negative
      feedback of sarcoplasmic reticulum Ca(2+) release on I(Ca-L) inactivation while
      others provide evidence for activation of calmodulin kinase II (CaMKII). To
      further elucidate the role of endogenous CaMKII activity, the CaMKII inhibitory
      peptides, autocamtide-2 relating inhibitory peptide (AIP) and myristoylated AIP
      were applied using conventional and perforated patch-clamp methods. AIP inhibited
      the normal adaptive increase in I(Ca-L) in response to abrupt increase in pacing
      frequency from 0.05 to 2 Hz. The positive I(Ca-L)-frequency relationship was
      reversed by AIP and the inhibitory effect of AIP was significantly exaggerated at
      fast pacing rates. The onset of inactivation of I(Ca-L) was not altered by AIP.
      After thapsigargin treatment, AIP slowed recovery from inactivation of I(Ca-L)
      and this effect was exaggerated during fast pacing. Buffering of [Ca(2+)](i) by
      BAPTA and EGTA accelerated recovery of I(Ca-L) from inactivation, and BAPTA
      partly eliminated the effect of AIP on the recovery. We conclude that: (1)
      [Ca(2+)](i) directly slows I(Ca-L) recovery from inactivation; and (2) Ca(2+)
      dependent endogenous CaMKII activity accelerates the I(Ca-L) recovery. Thus, at
      fast heart rates, elevated [Ca(2+)](i) activates endogenous CaMKII and
      compensates for its direct inhibitory effect on I(Ca-L) recovery from
      inactivation. Dynamic activity of endogenous CaMKII enhances the positive I(Ca-L)
      frequency relationship.

PMID- 16627566
TI  - Corticothalamic 5-9 Hz oscillations are more pro-epileptogenic than sleep
      spindles in rats.
AB  - Absence-related spike-and-wave discharges (SWDs) occur in the thalamocortical
      system during quiet wakefulness or drowsiness. In feline generalized penicillin
      epilepsy, SWDs develop from sleep spindles. In contrast, in genetic absence
      epilepsy rats from Strasbourg (GAERS), SWDs develop from wake-related 5-9 Hz
      oscillations, which are distinct from spindle oscillations (7-15 Hz). Since these
      two oscillation types share common frequency bands and may contribute to SWD
      genesis, it is important to compare their thalamic cellular mechanisms. Under
      neuroleptic analgesia, in GAERS and control non-epileptic rats barbiturates
      abolished both SWDs and 5-9 Hz oscillations but increased the incidence of
      spindle-like oscillations. Within the thalamocortical circuit 5-9 Hz oscillations
      occurred more coherently than spindle-like oscillations. Intracellular events
      associated with 5-9 Hz and spindle-like oscillations were distinctively different
      in both thalamic relay and reticular neurons. In both cell types, SWDs and 5-9 Hz
      oscillations emerged from a significantly more depolarized membrane potential
      than spindle-like oscillations. In relay neurons, 5-9 Hz oscillations were mainly
      characterized by a rhythmic depolarization, which occurred during a tonic
      hyperpolarization and which could trigger an apparent low-threshold Ca2+
      potential, whereas spindle-like oscillations were characterized by a rhythmic
      hyperpolarization. In reticular cells, SWDs and 5-9 Hz oscillations occurred
      during a tonic hyperpolarization, whereas spindle-like oscillations occurred
      during a long-lasting depolarizing envelope. The difference in the intracellular
      events between 5-9 Hz and spindle-like oscillations and similarities between 5-9
      Hz oscillations and SWDs indicate that in GAERS, 5-9 Hz oscillations are more pro
      epileptogenic than spindle-like oscillations. In conclusion, the present study
      strongly supports the hypothesis that SWDs in GAERS are generated by a wake
      related corticothalamic resonance, and not by sleep-related, hypersynchronous,
      spindle-like activity originating in the thalamus.

PMID- 16627567
TI  - GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse
      hypothalamus.
AB  - Hypocretin/orexin (Hcrt) is a critical neurotransmitter for the maintenance of
      wakefulness and has been implicated in several other functions, including energy
      metabolism and reward. Using whole-cell patch-clamp recordings from transgenic
      mice in which enhanced green fluorescent protein was linked to the Hcrt promoter,
      we investigated GABAergic control of the Hcrt neurones in hypothalamic slices.
      Bath application of GABA or muscimol caused an early hyperpolarization mediated
      by Cl(-) and a late depolarization mediated by the efflux of bicarbonate. These
      GABA(A) receptor-mediated responses were blocked by picrotoxin and bicuculline.
      Under the GABA(A) blockade condition, GABA produced consistent hyperpolarization,
      decreased firing rate and input resistance. The selective GABA(B) agonist (R)
      baclofen caused a similar response with an EC(50) of 7.1 mum. The effects of (R)
      baclofen were blocked by the GABA(B) antagonist CGP 52432 but persisted in the
      presence of tetrodotoxin, suggesting direct postsynaptic effects. The existence
      of GABA(B) modulation was supported by GABA(B(1)) subunit immunoreactivity on
      Hcrt cells colabelled with antisera to the Hcrt-2 peptide. Furthermore, GABA(B)
      receptor activation inhibited the presynaptic release of both glutamate and GABA.
      (R)-Baclofen depressed the amplitude of evoked excitatory postsynaptic currents
      (EPSCs) and inhibitory synaptic currents (IPSCs), and also decreased the
      frequency of both spontaneous and miniature EPSCs and IPSCs with a modest effect
      on their amplitudes. These data suggest that GABA(B) receptors modulate Hcrt
      neuronal activity via both pre- and postsynaptic mechanisms, which may underlie
      the promotion of non-rapid eye movement sleep and have implications for the use
      of GABA(B) agonists in the treatment of substance addiction through direct
      interaction with the Hcrt system.

PMID- 16627568
TI  - Molecular interactions between dipeptides, drugs and the human intestinal H+ 
      oligopeptide cotransporter hPEPT1.
AB  - The human intestinal proton-coupled oligopeptide transporter hPEPT1 has been
      implicated in the absorption of pharmacologically active compounds. We have
      investigated the interactions between a comprehensive selection of drugs, and
      wild-type and variant hPEPT1s expressed in Xenopus oocytes, using radiotracer
      uptake and electrophysiological methods. The beta-lactam antibiotics ampicillin,
      amoxicillin, cephalexin and cefadroxil, the antineoplastics delta-aminolevulinic
      acid (delta-ALA) and bestatin, and the neuropeptide N-acetyl-Asp-Glu (NAAG), were
      transported, as judged by their ability to evoke inward currents. When the drugs
      were added in the presence of the typical substrate glycylsarcosine (Gly-Sar),
      the inward currents were equal or less than that induced by Gly-Sar alone. This
      suggests that the drugs are transported at a lower turnover rate than Gly-Sar,
      but may also point towards complex interactions between dipeptides, drugs and the
      transporter. Gly-Sar and the drugs also modified the kinetics of hPEPT1 presteady
      state charge movement, by causing a reduction in maximum charge (Qmax) and a
      shift of the midpoint voltage (V0.5) to more negative potentials. Our results
      indicate that the substrate selectivity of hPEPT1 is: Gly-Sar > NAAG, delta-ALA,
      bestatin > cefadroxil, cephalexin > ampicillin, amoxicillin. Based on steady
      state and presteady-state analysis of Gly-Sar and cefadroxil transport, we
      proposed an extension of the 6-state kinetic model for hPEPT1 function that
      globally accounts for the observed presteady-state and steady-state kinetics of
      neutral dipeptide and drug transport. Our model suggests that, under saturating
      conditions, the rate-limiting step of the hPEPT1 transport cycle is the
      reorientation of the empty carrier within the membrane. Variations in rates of
      drug cotransport are predicted to be due to differences in affinity and turnover
      rate. Oral availability of drugs may be reduced in the presence of physiological
      concentrations of dietary dipeptides in the gut, suggesting that oral delivery
      drugs should be taken on an empty stomach. The common hPEPT1 single-nucleotide
      polymorphisms Ser117Asn and Gly419Ala retained the essential kinetic and drug
      recognition characteristics of the wild type, suggesting that neither variant is
      likely to have a major impact on oral absorption of drugs.

PMID- 16627569
TI  - Impaired overload-induced muscle growth is associated with diminished
      translational signalling in aged rat fast-twitch skeletal muscle.
AB  - Impaired overload-induced protein synthesis and growth in aged fast-twitch
      skeletal muscle may result from diminished responsiveness of signalling
      intermediates controlling protein translation. Yet, potential age-related
      signalling decrements have never been examined in direct parallel with impaired
      overload-induced muscle growth in any model. To this end, we used Western
      blotting to examine the contents and phosphorylation states of mammalian target
      of rapamycin (mTOR) and its downstream translational signalling intermediates, 70
      kDa ribosomal protein S6 kinase (S6k), ribosomal protein S6 (rpS6), eukaryotic
      elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1
      (4E-BP1), in conjunction with impaired growth in 1 week overloaded fast-twitch
      plantaris muscles (via unilateral gastrocnemius ablation) of old (O; 30 months)
      versus young adult (YA; 8 months) male Fischer344 x Brown Norway rats. The
      significantly (P <or= 0.05) diminished growth (assessed by total muscle protein
      content) in overloaded O muscles (5.6 +/- 1.7 versus 19.3 +/- 2.9% in YA) was
      accompanied by significant impairments in the phosphorylation states of mTOR
      (Ser2448), S6k (impaired at the mTOR-specific Thr389 residue but not at
      Thr421/Ser424), rpS6 (Ser235/236) and 4E-BP1 (gel shift), as well as deficits in
      total eEF2 accretion. Moreover, in overloaded muscles across both age groups,
      phospho-S6k at Thr389 (but not at Thr421/Ser424), 4E-BP1 phosphorylation status,
      and total eEF2 accretion were all positively correlated with percentage muscle
      hypertrophy, and negatively correlated with the phosphorylation (Thr172) of 5'
      AMP-activated protein kinase (AMPK; which inhibits translational signalling and
      protein synthesis in young muscle at rest). As previously published by ourselves,
      AMPK was hyperphosphorylated in O versus YA muscles used in the current
      investigation. The present results provide solid evidence that impaired overload
      induced growth in aged fast-twitch muscle may partly result from multiple-level
      decrements in signalling pathway(s) controlling protein translation, and also
      provide an initial indication that AMPK hyperactivation with age may potentially
      lie upstream of these decrements.

PMID- 16627570
TI  - Tmc1 is necessary for normal functional maturation and survival of inner and
      outer hair cells in the mouse cochlea.
AB  - The deafness (dn) and Beethoven (Bth) mutant mice are models for profound
      congenital deafness (DFNB7/B11) and progressive hearing loss (DFNA36),
      respectively, caused by recessive and dominant mutations of transmembrane
      cochlear-expressed gene 1 (TMC1), which encodes a transmembrane protein of
      unknown function. In the mouse cochlea Tmc1 is expressed in both outer (OHCs) and
      inner (IHCs) hair cells from early stages of development. Immature hair cells of
      mutant mice seem normal in appearance and biophysical properties. From around P8
      for OHCs and P12 for IHCs, mutants fail to acquire (dn/dn) or show reduced
      expression (Bth/Bth and, to a lesser extent Bth/+) of the K+ currents which
      contribute to their normal functional maturation (the BK-type current IK,f in
      IHCs, and the delayed rectifier IK,n in both cell types). Moreover, the
      exocytotic machinery in mutant IHCs does not develop normally as judged by the
      persistence of immature features of the Ca2+ current and exocytosis into
      adulthood. Mutant mice exhibited progressive hair cell damage and loss. The
      compound action potential (CAP) thresholds of Bth/+ mice were raised and
      correlated with the degree of hair cell loss. Homozygous mutants (dn/dn and
      Bth/Bth) never showed CAP responses, even at ages where many hair cells were
      still present in the apex of the cochlea, suggesting their hair cells never
      function normally. We propose that Tmc1 is involved in trafficking of molecules
      to the plasma membrane or serves as an intracellular regulatory signal for
      differentiation of immature hair cells into fully functional auditory receptors.

PMID- 16627571
TI  - Crossbridge and non-crossbridge contributions to tension in lengthening rat
      muscle: force-induced reversal of the power stroke.
AB  - Lengthening of active muscle is an essential feature of animal locomotion, but
      the molecular processes occurring are incompletely understood. We therefore
      examined and modelled tension responses to ramp stretches (5% fibre length, L0)
      over a wide range of velocities (0.1-10 L(0) s(-1)) of tetanized intact rat
      muscle fibre bundles (L0 approximately 2 mm) with a resting sarcomere length of
      2.5 microm at 20 degrees C. Tension rose to a peak during stretch and decayed
      afterwards to a level which was higher than the prestretch tetanic tension. This
      residual force enhancement was insensitive to velocity. The tension rise during
      stretch showed an early transition (often appearing as an inflection) at
      approximately 1 ms. Both the stretch (L1) and the tension rise at this transition
      increased in proportion to velocity. A second transition, marked by a reduction
      in slope, occurred at a stretch of approximately 18 nm per half-sarcomere; the
      rise in tension at this transition increased with velocity towards a plateau.
      Based on analyses of the velocity dependence of the tension and modelling, we
      propose that the initial steep increase in tension arises from increasing strain
      of all attached crossbridges and that the first transition reflects the tension
      loss due to the original post-stroke heads executing a reverse power stroke.
      Modelling indicates that the reduction in slope at the second transition occurs
      when the last of the heads that were attached at the start of the ramp become
      detached. Thereafter, the crossbridge cycle is largely truncated, with prepower
      stroke crossbridges rapidly detaching at high strain and attaching at low strain,
      the tension being borne mainly by the prestroke heads. Analysis of the tension
      decay after the ramp and the velocity dependence of the peak tension suggest that
      a non-crossbridge component increasingly develops tension throughout the stretch;
      this decays only slowly, reaching at 500 ms after the ramp approximately 20% of
      its peak value. This is supported by the finding that, in the presence of 10
      microm N-benzyl-p-toluene sulphonamide (a myosin inhibitor), while isometric
      tension is reduced to approximately 15%, and the crossbridge contribution to
      stretch-induced tension rise is reduced to 30-40%, the peak non-crossbridge
      contribution and the residual force enhancement remain high. We propose that the
      residual force enhancement is due to changes upon activation in parallel elastic
      elements, specifically that titin stiffens and C-protein-actin interactions may
      be recruited.

PMID- 16627572
TI  - 17Beta-oestradiol enhances the acute hypotensive effect of captopril in female
      ovariectomized spontaneously hypertensive rats.
AB  - The objective of this study was to investigate whether the acute haemodynamic
      effects of angiotensin-converting enzyme inhibition with captopril could be
      enhanced by oestrogen administration, and then to evaluate the mechanisms
      involved in this enhancement. All experiments were performed in 18-week-old
      female spontaneously hypertensive rats arranged in three experimental groups:
      intact; ovariectomized (OVX); and ovariectomized plus treatment with 17beta
      oestradiol (OVX + E2). These groups were used to evaluate the effects of
      captopril administration alone, or following bradykinin B2 receptor blockade or
      nitric oxide synthase inhibition, on a number of haemodynamic parameters (mean
      arterial pressure, cardiac index, vascular resistance and heart rate). The drop
      in mean arterial pressure and vascular resistance index in response to captopril
      was more pronounced in intact and ovariectomized rats treated with 17beta
      oestradiol than in ovariectomized animals. Blockade of bradykinin B2 receptors or
      inhibition of nitric oxide synthesis attenuated the synergy between 17beta
      oestradiol and captopril. It is concluded that ovariectomy blunted the blood
      pressure and vascular resistance index drop observed in intact rats in response
      to captopril. Treatment with 17beta-oestradiol prevented the blunted response to
      captopril in ovariectomized rats. Kinins and nitric oxide may be involved in the
      mechanisms of 17beta-oestradiol potentiation of the haemodynamic effects of
      captopril.

PMID- 16627573
TI  - Effect of short-term starvation versus high-fat diet on intramyocellular
      triglyceride accumulation and insulin resistance in physically fit men.
AB  - It is currently believed that intramyocellular triglyceride (IMTG) accumulation
      and insulin resistance are a consequence of dietary fat ingestion and/or the
      elevated circulating lipid levels associated with chronic fat surplus. The
      purpose of this study was to compare the effect of short-term starvation versus
      low-carbohydrate (CHO)/high-fat diet on IMTG accumulation and the development of
      insulin resistance in physically fit men. Intramyocellular triglyceride content,
      measured as intramyocellular lipid (IMCL) by proton magnetic resonance
      spectroscopy (1H-MRS), and glucose tolerance/insulin sensitivity, assessed by
      frequently sampled intravenous glucose tolerance test (IVGTT), were determined
      after 67 h of: (a) water-only starvation (S); and (b) very low-CHO/high-fat diet
      (LC). These diets had in common significant restriction of CHO availability but
      large differences in fat content. All results were compared with those measured
      after a mixed CHO diet (C). Dietary interventions were administered by cross-over
      design. The level of dietary-induced IMTG accumulation (P = 0.46), insulin
      resistance (P = 0.27) and glucose intolerance (P = 0.29) was not different
      between S and LC treatments. Intramyocellular triglyceride content and insulin
      sensitivity were negatively correlated (r = -0.63, P < 0.01). Therefore, whilst
      insulin resistance may be due to fat accumulation at a cellular level, in the
      integrated human organism this outcome is not exclusively a function of dietary
      fat intake. The comparable level of IMTG accumulation and insulin resistance
      following S and LC may suggest that these metabolic perturbations are largely a
      consequence of the increased lipolytic response associated with CHO restriction.

PMID- 16627574
TI  - Effect of transdermal nicotine administration on exercise endurance in men.
AB  - Nicotine is widely reported to increase alertness, improve co-ordination and
      enhance cognitive performance; however, to our knowledge there have been no
      attempts to replicate these findings in relation to exercise endurance. The
      purpose of this study was to determine the effects nicotine might have on cycling
      endurance, perception of exertion and a range of physiological variables. With
      local ethics committee approval and having obtained informed consent, 12 healthy,
      non-smoking men (22 +/- 3 years; maximal O2 uptake, 56 +/- 6 ml kg(-1) min(-1),
      mean +/- s.d.) cycled to exhaustion at 18 degrees C and 65% of their peak aerobic
      power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour-matched
      placebo (PLA) in a randomized cross-over design; water was available ad libitum.
      Subjects were exercising at approximately 75% of their maximal O2 uptake with no
      differences in cadence between trials. Ten out of 12 subjects cycled for longer
      with NIC administration, and this resulted in a significant 17 +/- 7% improvement
      in performance (P < 0.05). No differences were observed for perceived exertion,
      heart rate or ventilation. There were no differences in concentrations of plasma
      glucose, lactate or circulating fatty acids. In the absence of any effect on
      peripheral markers, we conclude that nicotine prolongs endurance by a central
      mechanism. Possible modes of action are suggested.

PMID- 16627575
TI  - Glucose-induced incretin hormone release and inactivation are differently
      modulated by oral fat and protein in mice.
AB  - Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins,
      especially whey protein (WP), have insulinotropic effects and can reduce
      postprandial glycemia. This effect may involve the incretin hormones glucose
      dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
      To explore this, we examined the release and inactivation of GIP and GLP-1 after
      administration of glucose with or without OA or WP through gastric gavage in
      anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold
      augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced
      oral glucose tolerance (P < 0.01). The insulin response to glucose was also
      augmented by addition of OA (34 mg; P < 0.05) although only 1.5-fold and with no
      associated increase in glucose elimination. The slope of the glucose-insulin
      curve was increased by OA (1.7-fold; P < 0.05) and by WP (4-fold; P < 0.01)
      compared with glucose alone, suggesting potentiation of glucose-stimulated
      insulin release. WP increased GLP-1 secretion (P < 0.01), whereas GIP secretion
      was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP
      increased the levels of both intact GIP and intact GLP-1 (both P < 0.01), and OA
      increased the levels of intact GLP-1 (P < 0.05). WP inhibited dipeptidyl
      peptidase IV activity in the proximal small intestine by 50% (P < 0.05),
      suggesting that luminal degradation of WP generates small fragments, which are
      substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We
      therefore conclude that fat and protein may serve as exogenous regulators of
      secretion and inactivation of the incretin hormones with beneficial influences on
      glucose metabolism.

PMID- 16627576
TI  - Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle
      promoting obesity.
AB  - The relation between blood taurine (2-aminoethanesulfonic acid) concentrations
      and obesity was investigated. Taurine is supplied to the body by dietary
      ingestion as well as by de novo synthesis; it is anabolized by cysteine
      dioxygenase (CDO), which is abundantly expressed in liver and white adipose
      tissue. Overexpression of CDO in 3T3-L1 preadipocytes caused a decrease in the
      level of cysteine (precursor of taurine) and an increase in the level of taurine
      in the culture medium, suggesting that CDO is involved in biosynthesis and
      secretion of taurine in white adipose tissue. In high-fat diet-induced and/or
      genetically obese mice, a decrease in the blood taurine concentration was
      observed along with a decrease in CDO expression in adipose tissue but not in
      liver. Dietary taurine supplementation prevented high-fat diet-induced obesity
      with increased resting energy expenditure. Thus, taurine deficiency observed in
      association with obesity may create a vicious circle promoting obesity. Dietary
      taurine supplementation interrupts this vicious circle and may prevent obesity.

PMID- 16627577
TI  - Bacterial lipopolysaccharide stimulates the thyrotropin-dependent thyroglobulin
      gene expression at the transcriptional level by involving the transcription
      factors thyroid transcription factor-1 and paired box domain transcription factor
      8.
AB  - The bacterial lipopolysaccharide (LPS) is a biological activator that induces
      expression of multiple genes in several cell types. LPS has been proposed as an
      etiopathogenic agent in autoimmune diseases. However, whether LPS affects the
      expression of autoantigens has not been explored. Thyroglobulin (TG) is a key
      protein in thyroid hormonogenesis and one of the major thyroid autoantigens. This
      study aimed to analyze the action of LPS on TG gene expression in Fisher rat
      thyroid cell line FRTL-5 thyroid cells. We demonstrate that LPS increases the TSH
      induced TG protein and mRNA level. Evidence that the effect of LPS is exerted at
      the transcriptional level was obtained by transfecting the minimal TG promoter.
      The C element of the TG promoter, which contains sequences for paired box domain
      transcription factor 8 (Pax8) and thyroid transcription factor (TTF)-1 binding,
      is essential for full TG promoter expression under TSH stimulation. The
      transcriptional activity of a construct containing five tandem repeats of the C
      site is increased by LPS, indicating a possible involvement of the C site in the
      LPS-induced TG gene transcription. We demonstrate that the TG promoter mutated at
      the Pax8 or TTF-1 binding element in the C site does not respond to LPS. In band
      shift assays, binding of Pax8 and TTF-1 to the C site is increased by LPS. The
      Pax8 and TTF-1 mRNA and protein levels are augmented by LPS. The half-lives of
      TG, Pax8, and TTF-1 are increased in endotoxin-treated cells. Our results reveal
      the ability of LPS to stimulate the expression of TG, a finding of potential
      pathophysiological implication.

PMID- 16627578
TI  - Mineralocorticoid receptor blockade but not steroid withdrawal reverses renal
      fibrosis in deoxycorticosterone/salt rats.
AB  - The pathophysiologic effects of nonepithelial mineralocorticoid receptor (MR)
      activation include vascular inflammation followed by renal and cardiac remodeling
      in experimental animals. We have recently shown that MR blockade can reverse
      established cardiac fibrosis and vascular inflammation; the present study
      explores whether a similar protection is seen in renal tissue. Rats were
      uninephrectomized and maintained on 0.9% NaCl solution to drink and treated as
      follows: control, vehicle; deoxycorticosterone (DOC), 20 mg/wk sc for 4 wk and
      then killed; DOC for 8 wk; DOC for 4 wk and no steroid for wk 5-8; DOC for 8 wk
      and eplerenone 100 mg/kg.d in the food for wk 5-8. DOC increased renal collagen
      at 4 and 8 wk; rats given DOC for 4 wk and killed at 8 wk showed levels of
      fibrosis identical with those killed at 4 wk, whereas rats given DOC for 8 wk
      plus eplerenone for wk 5-8 were indistinguishable from control. The inflammatory
      markers ED-1, osteopontin, and cyclooxygenase-2 remained significantly elevated
      despite the withdrawal of DOC (DOC404), whereas eplerenone restored
      cyclooxygenase-2 expression (but not that of ED-1 or osteopontin) to control
      levels. In addition, markers of oxidative stress and TGFbeta were determined. We
      hypothesize that continuing tubular inflammation and fibrosis despite DOC
      withdrawal indicates that the renal tissue may reflect MR activation in the
      context of tissue damage.

PMID- 16627579
TI  - Ablation of the glucagon receptor gene increases fetal lethality and produces
      alterations in islet development and maturation.
AB  - Although glucagon (GLU) plays a pivotal role in glucose homeostasis, its role in
      the regulation of fetal growth and maturation is poorly understood. These issues
      were examined in a line of mice with a global deletion of the GLU receptor (Gcgr
      /-), which are characterized by lower blood glucose levels and by alpha- and
      delta-cell hyperplasia in adults. Ablation of Gcgr was deleterious to fetal
      survival; it delayed beta-cell differentiation and perturbed the proportion of
      beta- to alpha-cells in embryonic islets. In adults, the mutation inhibited the
      progression of alpha-cells to maturity, affected the expression of several beta
      cell-specific genes, and resulted in an augmentation of the alpha-, beta-, and
      delta-cell mass. This increase was due to an augmentation in both islet number
      and in the rate of proliferation of cells expressing GLU or insulin. These
      findings suggest that GLU participates in a feedback loop that regulates the
      proportion of the different endocrine cell types in islets, the number of islets
      per pancreas, and development of the mature alpha-cell phenotype.

PMID- 16627580
TI  - The intraovarian actions of estrogen receptor-alpha are necessary to repress the
      formation of morphological and functional Leydig-like cells in the female gonad.
AB  - The predisposition of the testis and ovary to primarily synthesize testosterone
      (T) and estradiol (E2), respectively, is due to gonadal-specific cell types that
      differentially express the various hydroxysteroid (17beta) dehydrogenase (HSD17B)
      isoforms. In testes, Leydig cells rely on LH stimulation to maintain expression
      of the type 3 (HSD17B3) isoform, which specifically converts androstenedione to
      T. In ovaries, thecal interstitial (TI) cells also rely on LH to induce androgen
      synthesis but lack HSD17B3 and therefore secrete androgens of low biological
      activity. Therefore, thecal cells may possess a mechanism to repress the Leydig
      cell phenotype and HSD17B3 expression. E2 is known to inhibit experimentally
      Leydig cell function and proliferation. In the current study, we provide evidence
      that E2 prevents the development of functional Leydig-like cells in the murine
      ovary and that this action is mediated by estrogen receptor (ER) alpha. ERalpha
      null (alphaERKO) female mice exhibit testis-like levels of Hsd17b3 expression in
      the ovaries and male-like levels of plasma T. Herein, we demonstrate that: 1)
      Hsd17b3 expression in alphaERKO ovaries is a primary effect of the loss of
      intraovarian ERalpha actions; 2) alphaERKO ovarian cells produce substantial
      levels of T in vitro, and this is blocked by a HSD17B3-specific inhibitor; 3)
      Hsd17b3 expression in alphaERKO ovaries is LH regulated and localized to the
      secondary interstitial (SI)/TI cells; and 4) alphaERKO SI/TI cells possess Leydig
      like ultrastructural features. These data indicate that intraovarian ERalpha
      actions are required to repress Hsd17b3 expression in the ovary and may be
      important to maintaining a female phenotype in SI/TI cells.

PMID- 16627581
TI  - Osteoblasts provide a suitable microenvironment for the action of receptor
      activator of nuclear factor-kappaB ligand.
AB  - Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor
      activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis
      caused by enhanced bone resorption. Serum concentrations of RANKL are extremely
      high in OPG-deficient (OPG(-/-)) mice, suggesting that circulating RANKL is
      involved in osteoclastogenesis. RANKL(-/-) mice exhibit osteopetrosis, with the
      absence of osteoclasts. We examined the requirements for osteoclastogenesis using
      OPG(-/-) mice, RANKL(-/-) mice, and a system involving bone morphogenetic protein
      2 (BMP-2)-induced ectopic bone formation. When collagen disks containing BMP-2
      (BMP-2-disks) or vehicle were implanted into OPG(-/-) mice, osteoclast-like cells
      (OCLs) and alkaline phosphatase-positive OCLs appeared in BMP-2-disks but not the
      control disks. F4/80-positive osteoclast precursors were similarly distributed in
      both BMP-2- and control disks. Cells expressing RANKL were detected in the BMP-2
      disks, and the addition of OPG to the disk inhibited OCL formation. Muscle cells
      in culture differentiated into alkaline phosphatase-positive cells in the
      presence of BMP-2 and accordingly expressed RANKL mRNA in response to PTH. This
      suggests that RANKL expressed by osteoblasts is a requirement for
      osteoclastogenesis. We then examined how osteoblasts are involved in
      osteoclastogenesis other than RANKL expression, using RANKL(-/-) mice. BMP-2- and
      control disks were implanted into RANKL(-/-) mice, which were injected with RANKL
      for 7 d. Many OCLs were observed in the BMP-2-disks and bone tissues but not the
      control disks. These results suggest that osteoblasts also play important roles
      in osteoclastogenesis through offering the critical microenvironment for the
      action of RANKL.

PMID- 16627582
TI  - Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice
      with androgen receptor or follicle-stimulating hormone mutations.
AB  - The jsd mice experience a single wave of spermatogenesis, followed by an arrest
      of spermatogenesis because of a block in spermatogonial differentiation. Previous
      pharmacological and surgical studies have indicated that testosterone (T) and low
      scrotal temperatures but not FSH block spermatogonial differentiation in jsd
      mice. We sought to test these observations by genetic approaches by producing
      male jsd mutant mice with either defective androgen receptor (AR, Tfm mutation)
      or a deficiency of FSH (fshb(-/-)). In adult jsd-Tfm double-mutant mice, the
      tubule differentiation index was 95% compared with 14% in jsd littermates,
      suggesting that general ablation of AR function restored spermatogonial
      differentiation in jsd mice. The results indicated that this enhancement of
      differentiation was primarily a result of elevation of temperature caused by the
      cryptorchid position of the testis in jsd-Tfm double-mutant mice, which resulted
      from the lack of AR in the gubernaculum. The low levels of T were not a factor in
      the release of the spermatogonial differentiation block in the jsd-Tfm mice, but
      we were unable to determine whether inactivation of AR in the adult jsd testis
      had a direct effect on the restoration of spermatogonial differentiation because
      the elevated temperature bypassed the T-induced block in spermatogonial
      differentiation. Although spermatogonia were indeed present in adult jsd-fshb
      double-mutant mice and were capable of differentiation after androgen
      deprivation, these mice had a tubule differentiation index of 0%, ruling out the
      possibility that endogenous FSH inhibited spermatogonial differentiation in jsd
      mice. The results are consistent in support of the hypothesis that inhibition of
      spermatogonial differentiation in jsd mice is a result of T acting through the AR
      only at scrotal temperatures.

PMID- 16627583
TI  - Biological activity of follistatin isoforms and follistatin-like-3 is dependent
      on differential cell surface binding and specificity for activin, myostatin, and
      bone morphogenetic proteins.
AB  - Follistatin (FST) and FST-like-3 (FSTL3) are activin-binding and neutralization
      proteins that also bind myostatin. Three FST isoforms have been described that
      differ in tissue distribution and cell-surface binding activity, suggesting that
      the FST isoforms and FSTL3 may have some nonoverlapping biological actions. We
      produced recombinant FST isoforms and FSTL3 and compared their biochemical and
      biological properties. Activin-binding affinities and kinetics were comparable
      between the isoforms and FSTL3, whereas cell-surface binding differed markedly
      (FST288 > FST303 > FST315 > FSTL3). Inhibition of endogenous activin bioactivity,
      whether the FST isoforms were administered endogenously or exogenously,
      correlated closely with surface binding activity, whereas neutralization of
      exogenous activin when FST and FSTL3 were also exogenous was consistent with
      their equivalent activin-binding affinities. This difference in activin
      inhibition was also evident in an in vitro bioassay because FST288 suppressed,
      whereas FST315 enhanced, activin-dependent TT cell proliferation. Moreover, when
      FSTL3, which does not associate with cell membranes, was expressed as a membrane
      anchored protein, its endogenous activin inhibitory activity was dramatically
      increased. In competitive binding assays, myostatin was more potent than bone
      morphogenetic proteins (BMPs) 6 and 7, and BMPs 2 and 4 were inactive in binding
      to FST isoforms, whereas none of the BMPs tested competed with activin for
      binding to FSTL3. Neutralization of exogenous BMP or myostatin bioactivity
      correlated with the relative abilities of the isoforms to bind cell-surface
      proteoglycans. These results indicate that the differential biological actions
      among the FST isoforms and FSTL3 are primarily dependent on their relative cell
      surface binding ability and ligand specificity.

PMID- 16627584
TI  - Gonadotropin-releasing hormone activation of c-jun, but not early growth response
      factor-1, stimulates transcription of a luteinizing hormone beta-subunit gene.
AB  - Transcription of mammalian LH beta-subunit genes (LHbeta) is regulated by GnRH
      through activation of early growth response factor-1 (Egr-1), which interacts
      synergistically with steroidogenic factor-1 (Sf-1) and pituitary homeobox-1
      (Pitx1) at the promoter; Egr-1 is thought to comprise the major mediator of this
      effect. However, the proximal promoters of LHbeta genes in lower vertebrates lack
      an Egr-1 response element yet are responsive to GnRH; we demonstrate here that
      the promoter of the Chinook salmon LHbeta (csLHbeta) gene is also unresponsive to
      Egr-1. The homologous LHbeta promoters in other fish contain a conserved estrogen
      response element-like sequence, which we recently demonstrated is not required
      for estrogen receptor (ER) alpha association with the csLHbeta gene. Here we show
      that the estrogen response element-like element is required for the GnRH effect
      and for a response to c-jun overexpression. Using plasmid immunoprecipitation, we
      show that after GnRH exposure, c-jun associates with the intact csLHbeta gene
      promoter through this element. We further show that the effect of c-jun requires
      its DNA-binding domain and that c-jun interacts with Sf-1 and ERalpha and exerts
      synergistic effects on promoter activity with Sf-1, ERalpha, and Pitx1. Finally,
      we demonstrate the role of c-jun in mediating the GnRH effect on this gene
      through knockdown of c-jun expression or use of a dominant negative. We conclude
      that c-jun mediation of the GnRH effect on the LHbeta gene may be common in lower
      vertebrates and may have preceded an evolutionary divergence in the cis
      regulatory elements that led to its function being replaced in mammals by Egr-1.

PMID- 16627585
TI  - Deoxyribonucleic acid damage and spontaneous mutagenesis in the thyroid gland of
      rats and mice.
AB  - Thyroid tumors are a frequent finding not only in iodine-deficient regions. They
      are predominantly characterized by somatic genetic changes (e.g. point mutations
      or rearrangements). Because slow thyroid proliferation is a apparent
      contradiction to a high frequency of tumor initiation, we characterized
      mutational events in thyroid. First we studied the frequency of certain base
      exchanges in somatic TSH receptor (TSHR) mutations and determined the spontaneous
      mutation rate in thyroid and liver. Then we applied different protocols of the
      comet assay to quantify genomic DNA damage and conducted immunohistochemistry for
      8-oxoguanine as a molecular marker for oxidative stress. Among 184 somatic
      mutations of the human TSHR found in thyroid tumors, C-->T transitions had a
      unexpectedly high frequency (>32%). The mutation rate in thyroid is 8-10 times
      higher than in other organs. The comet assay detected increased levels of
      oxidized pyrimidine (2- to 3-fold) and purine (2- to 4-fold) in thyroid, compared
      with liver and lung, and a 1.6-fold increase of oxidized purine, compared with
      spleen. Immunohistochemistry revealed high levels of 8-oxoguanine in thyroid
      epithelial cells. We have shown a strikingly high mutation rate in the thyroid.
      Furthermore, results of the comet assay as well as immunohistochemistry suggest
      that oxidative DNA modifications are a likely cause of the higher mutation rate.
      It is possible that free radicals resulting from reactive oxygen species in the
      thyroid generate mutations more frequently. This is also supported by the
      spectrum of somatic mutations in the TSHR because more frequent base changes
      could stem from oxidized base adducts that we detected in the comet assay and
      with immunohistochemistry.

PMID- 16627586
TI  - Mining the mouse transcriptome of receptive endometrium reveals distinct
      molecular signatures for the luminal and glandular epithelium.
AB  - Epithelia coat most tissues where they sense and respond to the environment and
      participate in innate immune responses. In the adult mouse uterus, columnar
      epithelium lines the central lumen and the glands that penetrate the underlying
      stroma. A nidatory surge of estrogen causes differentiation of the luminal
      epithelium to the receptive state that permits blastocyst attachment and allows
      subsequent implantation. Here, using laser-capture microdissection to isolate the
      luminal and glandular epithelia separately, we have profiled gene expression 2 h
      before embryo attachment to determine whether there are unique roles for these
      two epithelial structures in this process. Although most genes were expressed in
      both compartments, there was greater expression of 153 and 118 genes in the lumen
      and glands, respectively. In the luminal epithelium, there is enrichment in
      lipid, metal-ion binding, and carbohydrate-metabolizing enzymes, whereas in the
      glands, immune response genes are emphasized. In situ hybridization to uterine
      sections obtained from mice during the preimplantation period validated these
      data and indicated an array of previously undocumented genes expressed with
      unique patterns in these epithelia. The data show that each epithelial
      compartment has a distinct molecular signature and that they act differentially
      and synergistically to permit blastocyst implantation.

PMID- 16627587
TI  - DAX-1 expression is regulated during mammary epithelial cell differentiation.
AB  - In recent studies, we have found that DAX-1 (dosage-sensitive sex
      reversal/adrenal hypoplasia congenita critical region on the X chromosome) is
      expressed in the mouse mammary epithelial cell line HC11. In this study, we
      focused on the regulation of DAX-1 expression and subcellular localization
      throughout mouse mammary epithelial cell differentiation and its hormonal
      regulation in the mouse mammary gland. Proliferating HC11 cells grown in
      epidermal growth factor (EGF)-containing medium, expressed very low levels of DAX
      1 as detected by Western blotting and quantitative real-time PCR, whereas, upon
      EGF withdrawal and induction of differentiation, DAX-1 expression increased.
      Inhibition of MAPK pathway with PD 098059 resulted in increased DAX-1 levels even
      in the presence of EGF. Using confocal microscopy, we showed that DAX-1
      cytoplasmic levels increased as cells differentiated. DAX-1 staining was nuclear
      in luminal cells of mouse mammary glands from 3-month-old virgin mice. A nucleo
      cytoplasmic pattern was observed in pseudopregnant mice and a cytoplasmic pattern
      was found in mammary glands from 6-d lactating mice. The influence of DAX-1 on
      transcriptional activity of endogenously expressed estrogen receptors alpha
      (ERalpha) and beta (ERbeta) in HC11 mammary epithelial cells was evaluated with
      an estrogen response element-luciferase reporter assay and by quantitative real
      time PCR of the ER-regulated gene receptor-interacting protein 140 kDa.
      Cotransfection of HC11 cells with human DAX-1 inhibited estrogen response element
      reporter and receptor-interacting protein 140 kDa expression induced by 17beta
      estradiol, the ERalpha-selective agonist 4,4',4'-(4-propyl-(1H)-pyrazole-1,3,5
      triyl)trisphenol, or the ERbeta-selective agonist 2,3-bis(4-hydroxyphenyl)
      propionitrile. In summary, DAX-1 expression increased upon differentiation
      induced by EGF withdrawal, and DAX-1 decreased response to estrogens in HC11
      cells. Further studies are needed to determine whether DAX-1 is also important in
      regulation of differentiation of HC11 cells.

PMID- 16627588
TI  - The role of intracerebroventricular administration of leptin in the stimulation
      of prothyrotropin releasing hormone neurons in the hypothalamic paraventricular
      nucleus.
AB  - We previously have shown that leptin regulates proTRH in the paraventricular
      nucleus (PVN) of the hypothalamus through two pathways. The first one acts
      directly on proTRH neurons, and the second one (indirect) acts through the
      melanocortin system (arcuate nucleus). However, it is unknown whether the direct
      or the indirect pathways of leptin action on proTRH neurons occurs on separated
      or on the same subsets of neurons within the PVN region. We used immunostaining
      for the phosphorylated signal transducer and activator of transcription 3 to
      localize direct leptin signaling, and the phosphorylated cAMP response element
      binding protein to localize indirect signaling on proTRH neurons in animals
      intracerebroventricularly injected with leptin. With this approach we were able
      to identify two subsets of neuronal populations responsive to leptin, which are
      distributed in different regions within the PVN. ProTRH neurons directly
      responsive to leptin were located mainly in the medial and posterior part of the
      PVN, and they were not primarily related to the hypothalamic pituitary thyroid
      axis. Whereas, proTRH neurons indirectly responsive (through alpha-MSH) to leptin
      were located mainly in the anterior, medial, and periventricular part of the PVN,
      and related to the hypothalamic pituitary thyroid axis. In addition, alpha-MSH
      showed to affect the processing of proTRH and up-regulated the prohormone
      convertase 1/3. In this study, we show evidence supporting the hypothesis that in
      the PVN there are subpopulations of proTRH neurons responding to leptin, which is
      dependent upon the way leptin reaches its primary target(s) in the hypothalamus.
      These findings are critical to a better understanding of leptin-mediated actions
      in energy expenditure.

PMID- 16627589
TI  - RGS2 is regulated by angiotensin II and functions as a negative feedback of
      aldosterone production in H295R human adrenocortical cells.
AB  - Regulator of G protein signaling (RGS) proteins interact with Galpha-subunits of
      heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and finalizing
      the intracellular signaling triggered by the G protein-coupled receptor-ligand
      interaction. Angiotensin (Ang) II interacts with its G protein-coupled receptor
      in zona glomerulosa adrenal cells and triggers a cascade of intracellular signals
      that regulates steroidogenesis and proliferation. We studied Ang II-mediated
      regulation of RGS2, the role of RGS2 in steroidogenesis, and the intracellular
      signal events involved in H295R human adrenal cells. We report that both H295R
      cells and human adrenal gland express RGS2 mRNA. In H295R cells, Ang II caused a
      rapid and transient increase in RGS2 mRNA levels quantified by real-time RT-PCR.
      Ang II effects were mimicked by calcium ionophore A23187 and blocked by calcium
      channel blocker nifedipine. Ang II effects also were blocked by calmodulin
      antagonists (W-7 and calmidazolium) and calcium/calmodulin-dependent kinase
      antagonist KN-93. RGS2 overexpression by retroviral infection in H295R cells
      caused a decrease in Ang II-stimulated aldosterone secretion but did not modify
      cortisol secretion. In reporter assays, RGS2 decreased Ang II-mediated
      aldosterone synthase up-regulation. These results suggest that Ang II up
      regulates RGS2 mRNA by the calcium/calmodulin-dependent kinase pathway in H295R
      cells. RGS2 overexpression specifically decreases aldosterone secretion through a
      decrease in Ang II-mediated aldosterone synthase-induced expression. In
      conclusion, RGS2 expression is induced by Ang II to terminate the intracellular
      signaling cascade generated by Ang II. RGS2 alterations in expression levels or
      functionality could be implicated in deregulations of Ang II signaling and
      abnormal aldosterone secretion by the adrenal gland.

PMID- 16627590
TI  - Regulation of the mouse protein targeting to glycogen (PTG) promoter by the FoxA2
      forkhead protein and by 3',5'-cyclic adenosine 5'-monophosphate in H4IIE hepatoma
      cells.
AB  - The scaffolding protein, protein targeting to glycogen (PTG), orchestrates the
      signaling of several metabolic enzymes involved in glycogen synthesis. However,
      little is known concerning the regulation of PTG itself. In this study, we have
      cloned and characterized the mouse promoter of PTG. We identified multiple FoxA2
      binding sites within this region. FoxA2 is a member of the forkhead family of
      transcription factors that has recently been implicated in the cAMP-dependent
      regulation of several genes involved in liver metabolism. Using luciferase
      reporter constructs, we demonstrate that FoxA2 transactivates the PTG promoter in
      H4IIE hepatoma cells. Nuclear extracts prepared from mouse liver and H4IIE cells
      were able to bind a FoxA2-specific probe derived within the PTG promoter region.
      Chromatin immunoprecipitation experiments further demonstrate that FoxA2 binds to
      the PTG promoter in vivo. Finally, we show that treatment with cAMP analogs
      activates the PTG promoter and significantly increases PTG levels in H4IIE cells.
      Our results provide a framework to investigate how additional transcription
      factors may regulate PTG expression in other cell types.

PMID- 16627591
TI  - Amphotericin B tissue distribution in autopsy material after treatment with
      liposomal amphotericin B and amphotericin B colloidal dispersion.
AB  - OBJECTIVES: Tissue concentrations of amphotericin B were determined in autopsy
      material of patients who had been treated with liposomal amphotericin B or
      amphotericin B colloidal dispersion (colloidal amphotericin B) for suspected or
      proven invasive fungal infection. PATIENTS AND METHODS: Amphotericin B tissue
      levels were measured in liver, spleen, lung, kidney, and myocardial and brain
      tissue of 20 patients who had been treated with lipid-formulated amphotericin B,
      before they died from multi-organ failure. Seven patients had been treated with
      liposomal amphotericin B (AmBisome) and thirteen with colloidal amphotericin B
      (Amphocil). Tissue samples were obtained during routine autopsy, homogenized and
      extracted with methanol. Amphotericin B concentrations were measured using HPLC
      after purification by solid phase extraction. RESULTS: The highest amphotericin B
      levels were found in liver and spleen, followed by kidney, lung, myocardium and
      brain. In the lung higher amphotericin B concentrations were found after
      treatment with amphotericin B colloidal dispersion than after therapy with
      liposomal amphotericin B. CONCLUSIONS: The choice of lipid formulation may
      influence amphotericin B penetration into the lung.

PMID- 16627592
TI  - Activity of newer triazoles against Histoplasma capsulatum from patients with
      AIDS who failed fluconazole.
AB  - OBJECTIVES: To determine the activity of newer triazoles against strains of
      Histoplasma capsulatum resistant to fluconazole. METHODS: Susceptibility testing
      was performed on 17 paired pre- and post-treatment H. capsulatum isolates from
      patients with AIDS who failed fluconazole. RESULTS: The median MICs of
      fluconazole, voriconazole, and posaconazole and ravuconazole for the pre
      treatment isolates were 1 mg/L, 0.015 mg/L and <0.007 mg/L, respectively. A 4
      fold or greater increase in the MIC of fluconazole and voriconazole was observed
      in 12 and 7 of the post-treatment isolates, respectively; the median fold
      increases in MIC were 8 and 2.1, respectively. No MIC increases were observed for
      posaconazole and ravuconazole. One pair of isolates exhibiting reduced
      susceptibility was examined in more detail. A single amino acid substitution (at
      tyrosine 136) was identified in the active site of the CYP51 protein from the
      post-treatment isolate, which is presumed to be responsible for reduced
      susceptibility to voriconazole and fluconazole, analogous to recent observations
      in Candida albicans. CONCLUSIONS: These findings support careful monitoring for
      relapse in patients receiving voriconazole treatment for histoplasmosis,
      particularly in those who were previously treated with fluconazole.

PMID- 16627593
TI  - Comparison of mortality of patients with Acinetobacter baumannii bacteraemia
      receiving appropriate and inappropriate empirical therapy.
AB  - OBJECTIVES: To evaluate the effect of inappropriate empirical antimicrobial
      treatment on the mortality of patients with Acinetobacter baumannii bacteraemia.
      METHODS: Retrospective cohort study of patients with A. baumannii bacteraemia
      hospitalized at the Henry Dunant hospital from January 2002 to December 2004.
      RESULTS: Among 40 patients with A. baumannii bacteraemia, 22 (55%) and 18 (45%)
      received inappropriate and appropriate antibiotic therapy, respectively, during
      the 3 day period after obtaining the blood culture(s) from which the pathogen was
      isolated. Failure to cure the infection was more common in the first group [16/22
      patients (72.7%) versus 5/18 (27.8%), P = 0.005]. Although without statistical
      significance, probably due to the small number of studied patients, considerably
      increased mortality was noted in the first group compared with the second group
      [13/22 patients (59.1%) versus 6/18 (33.3%), P = 0.10]. CONCLUSIONS: A. baumannii
      bacteraemia was associated with worse outcome regarding the cure of infection in
      patients who received inappropriate empirical antimicrobial treatment compared
      with those who received appropriate treatment.

PMID- 16627594
TI  - Long-term administration of estradiol decreases expression of hepatic lipogenic
      genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is
      through direct regulation of signal transducer and activator of transcription 3.
AB  - In this study, we used ob/ob mice as a model to investigate the effects of long
      term estradiol administration on insulin sensitivity and to explore the
      mechanisms that underlie the antidiabetic effects of estrogen on mouse liver.
      Female ob/ob mice were randomly divided into two groups and given estradiol (100
      microg/kg.d) or vehicle alone for 4 wk. Estrogen administration improved glucose
      tolerance and insulin response to glucose in ob/ob mice. Moreover, insulin
      resistance and liver triglyceride levels were decreased in response to estrogen
      administration. Microarray analysis revealed that expression of genes involved in
      hepatic lipid biosynthesis was decreased in ob/ob mouse livers after estradiol
      treatment. Further searches for direct estrogen target genes revealed increased
      hepatic mRNA expression of signal transducer and activator of transcription 3
      (Stat3) and several known Stat3 target genes in ob/ob livers after long-term
      estradiol treatment. Furthermore, Stat3 and phosphorylated Stat3 protein is
      induced in ob/ob mouse liver after long-term estrogen treatment. We also present
      data showing that Stat3 is rapidly induced by estradiol in mouse livers. This,
      together with data showing recruitment of ERalpha to the promoter of Stat3 in
      vivo, suggests that Stat3 is a direct target gene for estradiol. In conclusion,
      estradiol treatment improves glucose tolerance and insulin sensitivity in ob/ob
      mice. We propose that this may be mediated, at least partially, via estrogen
      stimulation of the hepatic expression of Stat3, leading to decreased expression
      of hepatic lipogenic genes, and thereby to antidiabetic effects.

PMID- 16627595
TI  - Androgen receptor ligand-binding domain interaction and nuclear receptor
      specificity of FXXLF and LXXLL motifs as determined by L/F swapping.
AB  - The androgen receptor (AR) ligand-binding domain (LBD) binds FXXLF motifs,
      present in the AR N-terminal domain and AR-specific cofactors, and some LXXLL
      motifs of nuclear receptor coactivators. We demonstrated that in the context of
      the AR FXXLF motif many different amino acid residues at positions +2 and +3 are
      compatible with strong AR LBD interaction, although a preference for E at +2 and
      K or R at +3 was found. Pairwise systematic analysis of F/L swaps at +1 and +5 in
      FXXLF and LXXLL motifs showed: 1) F to L substitutions in natural FXXLF motifs
      abolished AR LBD interaction; 2) binding of interacting LXXLL motifs was
      unchanged or increased upon L to F substitutions; 3) certain noninteracting LXXLL
      motifs became strongly AR-interacting FXXLF motifs; whereas 4) other nonbinders
      remained unaffected by L to F substitutions. All FXXLF motifs, but not the
      corresponding LXXLL motifs, displayed a strong preference for AR LBD.
      Progesterone receptor LBD interacted with some FXXLF motifs, albeit always less
      efficiently than corresponding LXXLL motifs. AR LBD interaction of most FXXLF and
      LXXLL peptides depended on classical charge clamp residue K720, whereas E897 was
      less important. Other charged residues lining the AR coactivator-binding groove,
      K717 and R726, modulated optimal peptide binding. Interestingly, these four
      charged residues affected binding of individual peptides independent of an F or L
      at +1 and +5 in swap experiments. In conclusion, F residues determine strong and
      selective peptide interactions with AR. Sequences flanking the core motif
      determine the specific mode of FXXLF and LXXLL interactions.

PMID- 16627596
TI  - Symmetrical muscle involvement in necrobiosis lipoidica.

PMID- 16627597
TI  - Proximal muscle weakness and elevated creatinine kinase.

PMID- 16627598
TI  - Nailfold capillaroscopic picture by chance.

PMID- 16627599
TI  - Cardiac tamponade ... a wire too far?

PMID- 16627600
TI  - Klotho, an important new factor for the activity of Ca2+ channels, connecting
      calcium homeostasis, ageing and uraemia.

PMID- 16627601
TI  - Cockroft-Gault or abbreviated-MDRD equations--which 'weighs' more in
      cardiovascular risk?

PMID- 16627602
TI  - Iliac cuffed tunnelled catheters for chronic haemodialysis vascular access.

PMID- 16627603
TI  - Renal glucose excretion as a function of blood glucose concentration in subjects
      with type 2 diabetes--results of a hyperglycaemic glucose clamp study.
AB  - BACKGROUND: The purpose of this study was to investigate renal glucose excretion
      as a function of blood glucose concentration and to evaluate the within-subject
      variability and between-subject variability in subjects with type 2 diabetes.
      METHODS: Twenty-two subjects with type 2 diabetes [age 58 (12) years, diabetes
      duration 7 (6) years, endogenous creatinine clearance 117 (38) ml min(-1) 1.73 m(
      2); median (inter-quartile range, IQR)] underwent two five-period hyperglycaemic
      glucose clamp experiments at intervals of 7-21 days. Starting from an initial
      blood glucose level of 12.2 mmol l(-1), subsequent glucose clamp levels were
      chosen using an algorithm based on urinary glucose concentrations measured at the
      end of the preceding glucose clamp period. That is, blood glucose was either
      stepwise decreased or increased depending on whether urinary glucose
      concentration was above or below 11.1 mmol l(-1), respectively. RESULTS: As
      expected, increasing the blood glucose from 7.8 to 13.3 mmol l(-1) during the
      glucose clamps resulted in a steep increase of urinary glucose excretion from
      0.06 to 0.77 mmol min(-1). With decreasing blood glucose, a measurable glucosuria
      persisted up to a blood glucose level of 7.8 mmol l(-1). When defining the
      (pseudo)threshold for renal glucose excretion (PRT(G)) as the highest blood
      glucose level during glucose clamps associated with a concomitant glucose
      concentration in urine of <2.8 mmol l(-1), median (IQR) PRT(G) was 11.0 (1.1)
      mmol l(-1). The within-subject variability of PRT(G), i.e. the difference between
      two assessments, was low, 0.1 (0.0) mmol l(-1) while the between-subject
      variability of PRT(G) was high, ranging from 7.7 to 12.2 mmol l(-1). CONCLUSION:
      Renal glucose excretion increases in a proportional manner with increasing blood
      glucose. When decreasing blood glucose to euglycaemic blood glucose levels,
      glucosuria persists so that the classical concept of a renal threshold for
      glucose excretion cannot be upheld in subjects with type 2 diabetes.

PMID- 16627604
TI  - Graft vs host disease following kidney transplantation using an '0 HLA antigen
      mismatched' donor.

PMID- 16627605
TI  - Clarithromycin-induced granulomatous tubulointerstitial nephritis.

PMID- 16627606
TI  - Catheter lock solutions influence staphylococcal biofilm formation on abiotic
      surfaces.
AB  - BACKGROUND: Microbial biofilms form on central venous catheters and may be
      associated with systemic infections as well as decreased dialysis efficiency due
      to catheter thrombosis. The most widely used anticoagulant catheter lock solution
      in the US is sodium heparin. We have previously shown that sodium heparin in
      clinically relevant concentrations enhances Staphylococcus aureus biofilm
      formation. In the present study, we examine the effect of several alternative
      catheter lock solutions on in vitro biofilm formation by laboratory and clinical
      isolates of S. aureus and coagulase-negative staphylococci (CNS). METHODS:
      Lepirudin, low molecular weight heparin, tissue plasminogen activator, sodium
      citrate, sodium citrate with gentamicin and sodium ethylene diamine tetra-acetic
      acid (EDTA) were assessed for their effect on biofilm formation on polystyrene,
      polyurethane and silicon elastomer. RESULTS: Sodium citrate at concentrations
      above 0.5% efficiently inhibits biofilm formation and cell growth of S. aureus
      and Staphylococcus epidermidis. Subinhibitory concentrations of sodium citrate
      significantly stimulate biofilm formation in most tested S. aureus strains, but
      not in CNS strains. Sodium EDTA was effective in prevention of biofilm formation
      as was a combination of sodium citrate and gentamicin. Low molecular weight
      heparin stimulated biofilm formation of S. aureus, while lepirudin and tissue
      plasminogen activator had little effect on S. aureus biofilm formation.
      CONCLUSIONS: This in vitro study demonstrates that heparin alternatives, sodium
      citrate and sodium EDTA, can prevent the formation of S. aureus biofilms,
      suggesting that they may reduce the risk of biofilm-associated complications in
      indwelling catheters. This finding suggests a biological mechanism for the
      observed improvement in catheter-related outcomes in recent clinical comparisons
      of heparin and trisodium citrate as catheter locking solutions. A novel and
      potential clinically relevant finding of the present study is the observation
      that citrate at low levels strongly stimulates biofilm formation by S. aureus.

PMID- 16627607
TI  - Costs and benefits of improving renal failure treatment--where do we go?

PMID- 16627608
TI  - Chylous pericardial tamponade in a haemodialysis patient with catheter-associated
      thrombosis of internal jugular and subclavian veins.

PMID- 16627609
TI  - Polynocturia in chronic kidney disease is related to natriuresis rather than to
      water diuresis.
AB  - BACKGROUND: Nocturnal polyuria has been well known in renal insufficiency.
      Recently, we found that as renal function deteriorated in chronic kidney disease
      (CKD), natriuresis was enhanced during the night with nocturnal blood pressure
      elevation. In the present study, we investigated whether nocturnal polyuria in
      CKD was due to the inability to concentrate urine, as previously proposed, or
      based on osmotic diuresis mainly by natriuresis. METHODS: In 27 CKD patients,
      circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates
      (U(Na)V, U(K)V, U(urea)V, U(osm)V) as well as of urinary volume (V) and free
      water clearance (C(H(2)O)) were estimated during both daytime (6:00 to 21:00) and
      nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were
      analysed in relation to creatinine clearance (C(cr)) as a marker of glomerular
      filtration rate. RESULTS: C(cr) had significantly negative relationships with
      night/day ratios of V (R = -0.69; P < 0.0001), U(osm)V (R = -0.54; P = 0.004) and
      U(Na)V (R = -0.63; P = 0.0005), but no correlation with night/day ratios of
      C(H(2)O) (R = -0.33; P = 0.1), U(K)V (R = -0.29; P = 0.1) or U(urea)V (R = -0.31;
      P = 0.1). Linear and multiple regression analysis identified nocturnal
      natriuresis rather than urea excretion as an independent determinant of nocturia.
      CONCLUSION: As renal function deteriorated, nocturnal polyuria was seen, being
      consistent with classical recognition. Furthermore, this increase in nocturnal
      urine volume seemed related to osmotic diuresis mainly by natriuresis rather than
      to water diuresis or urea excretion.

PMID- 16627610
TI  - Tubulointerstitial disease and ulcerative colitis.

PMID- 16627611
TI  - Aquaporin-1--a water channel on the move.

PMID- 16627612
TI  - Successful endovascular treatment of bilateral renal artery paradoxical embolus
      by a modified standard technique.

PMID- 16627613
TI  - Prolonged use of an intracardiac catheter for dialysis in a patient with multiple
      venous access failure.

PMID- 16627614
TI  - Improvement in open-angle glaucoma by nocturnal home haemodialysis.

PMID- 16627615
TI  - CMV prophylaxis--to do or not to do, that is the question.

PMID- 16627616
TI  - The long-term dialysis patient with purple-blue toes.

PMID- 16627617
TI  - TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity.
AB  - Target of rapamycin (TOR) plays a central role in cell growth regulation by
      integrating signals from growth factors, nutrients, and cellular energy levels.
      TOR forms two distinct physical and functional complexes, termed TOR complex 1
      (TORC1) and TOR complex 2 (TORC2). TORC1, which is sensitive to rapamycin,
      regulates translation and cell growth, whereas TORC2, which is insensitive to
      rapamycin, regulates cell morphology and cell growth. The Ras homology enriched
      in brain (Rheb) small GTPase is known to be a key upstream activator of TORC1,
      although the mechanism of Rheb in TORC1 activation remains to be determined.
      However, the function of Rheb in the TORC2 regulation has not been elucidated. By
      measuring Akt and S6K phosphorylation as a functional assay for TORC1 and -2,
      here, we report that dRheb has an inhibitory effect on dTORC2 activity in
      Drosophila S2 cells. This negative effect of dRheb on dTORC2 is possibly due to a
      feedback mechanism involving dTORC1 and dS6K. We also observed that Rheb does not
      activate TORC2 in human embryonic kidney 293 cells, although it potently
      stimulates TORC1. Furthermore, tuberous sclerosis complex 1 (TSC1) and TSC2,
      which are negative regulators of Rheb, have negative and positive effects on
      TORC1 and -2, respectively. Our observations suggest that TSC1/2 and Rheb have
      different effects on the activity of TORC1 and -2, further supporting the
      complexity of TOR regulation.

PMID- 16627618
TI  - The primary function of RNA binding by the influenza A virus NS1 protein in
      infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway.
AB  - The NS1 protein of influenza A virus (NS1A protein) is a multifunctional protein
      that counters cellular antiviral activities and is a virulence factor. Its N
      terminal RNA-binding domain binds dsRNA. The only amino acid absolutely required
      for dsRNA binding is the R at position 38. To identify the role of this dsRNA
      binding activity during influenza A virus infection, we generated a recombinant
      influenza A/Udorn/72 virus expressing an NS1A protein containing an RNA-binding
      domain in which R38 is mutated to A. This R38A mutant virus is highly attenuated,
      and the mutant NS1A protein, like the WT protein, is localized in the nucleus.
      Using the R38A mutant virus, we establish that dsRNA binding by the NS1A protein
      does not inhibit production of IFN-beta mRNA. Rather, we demonstrate that the
      primary role of this dsRNA-binding activity is to protect the virus against the
      antiviral state induced by IFN-beta. Pretreatment of A549 cells with IFN-beta for
      6 h did not inhibit replication of WT Udorn virus, whereas replication of R38A
      mutant virus was inhibited 1,000-fold. Using both RNA interference in A549 cells
      and mouse knockout cells, we show that this enhanced sensitivity to IFN-beta
      induced antiviral activity is due predominantly to the activation of RNase L.
      Because activation of RNase L is totally dependent on dsRNA activation of 2'-5'
      oligo (A) synthetase (OAS), it is likely that the primary role of dsRNA binding
      by the NS1A protein in virus-infected cells is to sequester dsRNA away from 2'-5'
      OAS.

PMID- 16627619
TI  - Homodimerization of the G protein SRbeta in the nucleotide-free state involves
      proline cis/trans isomerization in the switch II region.
AB  - Protein translocation across and insertion into membranes is essential to all
      life forms. Signal peptide-bearing nascent polypeptide chains emerging from the
      ribosome are first sampled by the signal-recognition particle (SRP), then
      targeted to the membrane via the SRP receptor (SR), and, finally, transferred to
      the protein-conducting channel. In eukaryotes, this process is tightly controlled
      by the concerted action of three G proteins, the 54-kD subunit of SRP and the
      alpha- and beta-subunits of SR. We have determined the 2.2-A crystal structure of
      the nucleotide-free SRbeta domain. Unexpectedly, the structure is a homodimer
      with a highly intertwined interface made up of residues from the switch regions
      of the G domain. The remodeling of the switch regions does not resemble any of
      the known G protein switch mechanisms. Biochemical analysis confirms
      homodimerization in vitro, which is incompatible with SRalpha binding. The switch
      mechanism involves cis/trans isomerization of a strictly conserved proline,
      potentially implying a new layer of regulation of cotranslational transport.

PMID- 16627620
TI  - Dysregulation of signaling pathways in CD45-deficient NK cells leads to
      differentially regulated cytotoxicity and cytokine production.
AB  - CD45, a protein tyrosine phosphatase that regulates Src family kinases, is
      important for regulating T cell and B cell receptor signaling; however, little is
      known about how CD45 regulates immunoreceptor tyrosine-based activation motif
      (ITAM)-dependent natural killer (NK) cell receptor signaling and the resulting
      effector functions. NK cells from CD45-deficient mice are relatively competent
      for ITAM receptor-induced cell-mediated cytotoxicity, yet completely deficient
      for cytokine secretion after stimulation with ligands to or antibodies against
      NK1.1, CD16, Ly49H, Ly49D, and NKG2D. This deficiency in cytokine/chemokine
      production occurs at the level of mRNA expression. After receptor engagement,
      extracellular signal-regulated kinase and c-Jun N-terminal kinase activation was
      markedly perturbed, whereas p38 activation was not substantially affected. The
      pattern and amounts of basal tyrosine phosphorylation were altered in freshly
      isolated NK cells and were surprisingly and markedly increased in IL-2-expanded
      NK cells from CD45-/- mice. These findings indicate that CD45-dependent
      regulation of ITAM-dependent signaling pathways is essential for NK cell-mediated
      cytokine production but not cytolytic activity.

PMID- 16627621
TI  - Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a
      modification associated with S phase in mitosis and meiosis.
AB  - Histone acetylation affects many nuclear processes including transcription,
      chromatin assembly, and DNA damage repair. Acetylation of histone H3 lysine 56
      (H3 K56ac) in budding yeast occurs during mitotic S phase and persists during DNA
      damage repair. Here, we show that H3 K56ac is also present during premeiotic S
      phase and is conserved in fission yeast. Furthermore, the H3 K56ac modification
      is not observed in the absence of the histone chaperone Asf1. asf1delta and H3
      K56R mutants exhibit similar sensitivity to DNA damaging agents. Mutational
      analysis of Asf1 demonstrates that DNA damage sensitivity correlates with (i)
      decreased levels of H3 K56ac and (ii) a region implicated in histone binding. In
      contrast, multiple asf1 mutants that are resistant to DNA damage display WT
      levels of K56ac. These data suggest that maintenance of H3 K56 acetylation is a
      primary contribution of Asf1 to genome stability in yeast.

PMID- 16627622
TI  - Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by
      extracellular signal-regulated kinases 1/2.
AB  - Sustained activation of poly(ADP-ribose) polymerase-1 (PARP-1) and extracellular
      signal-regulated kinases 1/2 (ERK1/2) both promote neuronal death. Here we
      identify a direct link between these two cell death pathways. In a rat model of
      hypoglycemic brain injury, neuronal PARP-1 activation and subsequent neuronal
      death were blocked by the ERK1/2 inhibitor 2-(2-amino-3-methoxyphenyl)-4H-1
      benzopyran-4-one (PD98059). In neuron cultures, PARP-1-mediated neuronal death
      induced by N-methyl-d-aspartate, peroxynitrite, or DNA alkylation was similarly
      blocked by ERK1/2 pathway inhibitors. These inhibitors also blocked PARP-1
      activation and PARP-1-mediated death in astrocytes. siRNA down-regulation of ERK2
      expression in astrocytes also blocked PARP-1 activation and cell death. Direct
      effects of ERK1/2 on PARP-1 were evaluated by using isolated recombinant enzymes.
      The activity of recombinant human PARP-1 was reduced by incubation with alkaline
      phosphatase and restored by incubation with active ERK1 or ERK2. Putative ERK1/2
      phosphorylation sites on PARP-1 were identified by mass spectrometry. Using site
      directed mutagenesis, these sites were replaced with alanine (S372A and T373A) to
      block phosphorylation, or with glutamate (S372E and T373E) to mimic constitutive
      phosphorylation. Transfection of PARP-1 deficient mouse embryonic fibroblasts
      with the mutant PARP-1 species showed that the S372A and T373A mutations impaired
      PARP-1 activation, whereas the S372E and T373E mutations increased PARP-1
      activity and eliminated the effect of ERK1/2 inhibitors on PARP-1 activation.
      These results suggest that PARP1 phosphorylation by ERK1/2 is required for
      maximal PARP-1 activation after DNA damage.

PMID- 16627623
TI  - Different allele-distribution of mthfr 677 C -> T and mthfr -393 C -> a in
      patients classified according to subtypes of Lesch's typology.
AB  - AIMS: The typology by Lesch distinguishes between four subtypes: type 1 (model of
      allergy), type 2 (model of anxiety or conflict), type 3 (alcohol as an
      antidepressant), and type 4 (alcohol as adaptation). Taking into account that
      alcohol dependence is associated with elevated homocysteine levels, this study
      was undertaken to investigate different MTHFR (methylenetetrahydrofolate
      reductase) genotypes related to homocysteine metabolism in patients with alcohol
      dependence who were classified according to Lesch's typology (LT). SUBJECTS AND
      METHODS: 134 non-abstinent chronic alcoholics (112 males, 22 females; mean age
      44.2 (SD 8.9) years) were classified according to LT and divided into four
      groups: LT 1 (n = 26), LT 2 (n = 65), LT 3 (n = 58), and LT 4 (n = 18). Total
      plasma homocysteine levels and MTHFR genotypes -393, 677, and 1,793 were
      determined. RESULTS: We observed a significantly higher frequency of the
      thermolabile MTHFR 677 C-->T variant (TT) in patients classified as subtype LT4
      when compared with subtypes LT2 and LT3 (P = 0.005). Furthermore, for the MTHFR 
      393 C --> A-polymorphism, significantly more AC/AA variants were found in subtype
      LT4 (P = 0.034). No differences in allele-distribution were detected for MTHFR
      1793. CONCLUSION: To our knowledge, this is the first study evaluating MTHFR
      genotypes in patients who were classified according to LT. Significantly
      different distributions of MTHFR 677 and -393 variants within Lesch Type 4 as
      compared with Types 2 and 3 hint at genetic determination of Lesch subtypes.

PMID- 16627624
TI  - A literature overview of the relationship between life-events and alcohol use in
      the general population.
AB  - AIMS: A critical review of the evidence of effects of stressful life-events on
      alcohol use in the general population, with a particular focus on study design.
      METHODS: A literature search in Medline was conducted, covering the period from
      1990 to 2005, to identify articles in which the relationship between life-events
      and alcohol use in the general population (i.e. non-problem drinking population)
      was investigated. Samples with a limited age range (e.g. college students) were
      excluded. Twelve studies with a cross-sectional design, and four articles with a
      longitudinal design were included in this review. RESULTS: Four cross-sectional
      studies found evidence that experiencing life-events is related to higher alcohol
      use, three other studies, however, found no such association. The relationship
      between specific life-events and alcohol use in the five remaining cross
      sectional studies is less clear-cut. Being a victim of crime was associated with
      higher alcohol use, but divorce and financial problems were related to both
      higher and lower alcohol use. Health-related life-events were found to be
      associated with lower alcohol use. In studies with a longitudinal design, it was
      found that health-related life-events and financial problems caused a decrease in
      alcohol use, and life-events related to spouse, friends and relatives, and
      retiring led to an increase in alcohol use. CONCLUSIONS: Evidence points towards
      a relationship between the occurrence of life-events and alcohol use in the
      general population. The direction of the effect is, however, not unequivocal.
      When life-events are operationalized or categorized separately they are not only
      related to an increased alcohol use but also to a decreased alcohol use.
      Specification of the model to be tested, including buffering factors such as
      gender, social support, coping resources, as well as baseline consumption, is
      important for a correct estimation of the effect of negative life-events.

PMID- 16627625
TI  - Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates
      heart failure progression in genetic cardiomyopathy.
AB  - The type 1 protein phosphatase (PP1) has been reported to be overactivated in the
      failing heart, leading to a depression in cardiac function. We investigated
      whether in vivo PP1 inhibition by myocardial gene transfer of inhibitor-2 (INH
      2), an endogenous PP1 inhibitor, alleviates heart failure (HF) progression in the
      cardiomyopathic (CM) hamster, a well-established HF model. Adenoviral INH-2 gene
      delivery improved % fractional shortening of the left ventricle (LV) accompanied
      by reduced chamber size at 1 wk. In vivo myocardial INH-2 gene delivery induced
      an increase in cytosolic PP1 catalytic subunit alpha (PP1Calpha) without inducing
      the corresponding increase in cytosolic PP1 activity. On the other hand, INH-2
      delivery induced a decrease in microsomal PP1Calpha, resulting in a preferential
      decrease in microsomal PP1 activity, thereby increasing in phospholamban
      phosphorylation at Ser16. INH-2 gene transfer alleviated brain natriuretic
      peptide expression, presumably reflecting improved cardiac function. Moreover,
      adeno-associated virus-mediated INH-2 gene delivery significantly extended the
      survival time for 3 mo. These results indicate that increased PP1 activity is an
      exacerbating factor during progression of genetic cardiomyopathy and modulation
      of PP1 activity by INH-2 provides a potential new treatment for HF without
      activating protein kinase A signaling in cardiomyocytes.

PMID- 16627626
TI  - Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal
      homeostasis.
AB  - Nicotine reduces beta-amyloidosis and has a beneficial effect against Alzheimer's
      disease (AD), but the underlying mechanism is not clear. The abnormal
      interactions of beta-amyloid (Abeta) with metal ions such as copper and zinc are
      implicated in the process of Abeta deposition in AD brains. In the present study,
      we investigated the effect of nicotine on metal homeostasis in the hippocampus
      and cortex of APP(V717I) (London mutant form of APP) transgenic mice. A
      significant reduction in the metal contents of copper and zinc in senile plaques
      and neuropil is observed after nicotine treatment. The densities of copper and
      zinc distributions in a subfield of the hippocampus CA1 region are also reduced
      after nicotine treatment. We further studied the mechanism of nicotine-mediated
      effect on metal homeostasis by using SH-SY5Y cells overexpressing the Swedish
      mutant form of human APP (APPsw). Nicotine treatment decreases the intracellular
      copper concentration and attenuates Abeta-mediated neurotoxicity facilitated by
      the addition of copper, and these effects are independent of the activation of
      nicotinic acetylcholine-receptor. These data suggest that the effect of nicotine
      on reducing beta-amyloidosis is partly mediated by regulating metal homeostasis.

PMID- 16627627
TI  - Child's play.

PMID- 16627628
TI  - High-energy extracorporeal shock wave therapy as a treatment for insertional
      Achilles tendinopathy.
AB  - BACKGROUND: Results of high-energy extracorporeal shock wave therapy for the
      treatment of insertional Achilles tendinopathy are not determined. It is unclear
      how local anesthesia alters the outcome of this procedure. HYPOTHESIS:
      Extracorporeal shock wave therapy is an effective treatment for insertional
      Achilles tendinopathy. Local anesthesia field block adversely affects outcome.
      STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Thirty-five
      patients with chronic insertional Achilles tendinopathy were treated with 1 dose
      of high-energy extracorporeal shock wave therapy (ESWT group; 3000 shocks; 0.21
      mJ/mm2; total energy flux density, 604 mJ/mm2), and 33 were treated with
      nonoperative therapy (control group). All extracorporeal shock wave therapy
      procedures were performed using a local anesthesia field block (LA subgroup, 12
      patients) or a nonlocal anesthesia (NLA subgroup, 23 patients). Evaluation was by
      visual analog score and by Roles and Maudsley score. RESULTS: One month, 3
      months, and 12 months after treatment, the mean visual analog score for the
      control and ESWT groups were 8.2 and 4.2 (P < .001), 7.2 and 2.9 (P < .001), and
      7.0 and 2.8 (P < .001), respectively. Twelve months after treatment, the number
      of patients with successful Roles and Maudsley scores was statistically greater
      in the ESWT group compared with the control group (P > .0002), with 83% of ESWT
      group patients having a successful result, and the mean improvement in visual
      analog score for the LA subgroup was significantly less than that in the NLA
      subgroup (F = 16.77 vs F = 53.95, P < .001). The percentage of patients with
      successful Roles and Maudsley scores did not differ among the LA and NLA
      subgroups. CONCLUSION: Extracorporeal shock wave therapy is an effective
      treatment for chronic insertional Achilles tendinopathy. Local field block
      anesthesia may decrease the effectiveness of this procedure.

PMID- 16627629
TI  - A prospective outcome evaluation of arthroscopic Bankart repairs: minimum 2-year
      follow-up.
AB  - BACKGROUND: Arthroscopic treatment of anterior shoulder dislocation has become
      possible through improvements in instruments and techniques. OBJECTIVE: To
      prospectively evaluate results of arthroscopic Bankart repairs at a minimum 2
      year follow-up for patients with histories of shoulder dislocation and an
      anterior-inferior labral tear at the time of diagnostic arthroscopy. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: A consecutive series of 85
      patients (70 men, 15 women; mean age, 26 years) with Bankart lesions were treated
      with arthroscopic repair using suture anchors; 18 patients (27%) had extension of
      the labral injury into the superior labrum affecting some or all of the biceps
      anchor. Anchors were loaded with no. 2 nonabsorbable braided suture and placed 2
      mm into the edge of the glenoid surface. A low anterior (5-o'clock) portal
      through the subscapularis tendon was used in all patients; 72 patients were
      evaluated at a minimum of 2 years postoperatively (mean, 46 months). RESULTS:
      Seven patients (10%) experienced recurrent instability after repair. Four
      patients had redislocations; 3 experienced recurrent subluxations. One patient
      had pain with the apprehension test without a clear history of recurrent
      instability. Of 18 collision athletes, 2 had dislocations at 22 and 60 months
      postoperatively. There were no complications, including no neurologic deficits.
      Clinical strength testing of the subscapularis muscle was normal in all patients.
      The mean Rowe score was 88 of 100 points, with 90% excellent or good results.
      Simple Shoulder Test responses improved from 66% positive preoperatively to 88%
      positive postoperatively. The American Shoulder and Elbow Surgeons scoring index
      averaged 92 of 100 points postoperatively. Pain analog scales improved from 5.5
      preoperatively to 0.35 postoperatively on a 10-point scale. SF-12 scores improved
      for physical function. Patient satisfaction was rated 8.9 on a 10-point visual
      analog scale. CONCLUSION: Bankart repairs performed arthroscopically using
      properly implanted suture anchors and nonabsorbable sutures and in which
      associated pathoanatomy is addressed demonstrate low recurrence rates (10%)
      similar to historical open controls.

PMID- 16627630
TI  - Avoiding sural nerve injuries during percutaneous Achilles tendon repair.
AB  - BACKGROUND: Sural nerve injury is a reported risk during percutaneous repair of
      the Achilles tendon. HYPOTHESIS: Exposure of the sural nerve during percutaneous
      repair can minimize the risk of nerve injury. STUDY DESIGN: Case control study;
      Level of evidence, 3. METHODS: The authors retrospectively examined the results
      of 84 patients who were treated for acute Achilles tendon rupture at 2 different
      hospitals. Both hospitals used the same percutaneous repair technique, except
      that the sural nerve was exposed in the 38 patients (mean age, 38 years; range,
      23-68 years) of one hospital; the nerve was not exposed in the 46 patients (mean
      age, 42 years; range, 24-71 years) of the other hospital (the nonexposure group).
      RESULTS: All patients recovered and returned to work after 44 days (range, 5-202
      days). All patients returned to their previous sports levels within 1 year. On
      the 100-point Hannover Achilles Tendon Score, the mean score was 81 points
      (range, 44-100 points). The overall incidence of sural nerve related
      complications was 18%. All sural nerve lesions occurred in the nonexposure group.
      In the total study population, there were 3 cases of deep vein thrombosis, 1
      rerupture, and 1 case of infection. CONCLUSION: Sural nerve injuries can be
      minimized during surgery by carefully placing the stab incisions to expose the
      nerve so as to avoid it during repair. If the sural nerve is exposed,
      percutaneous repair of the ruptured Achilles tendon is a safe and reliable method
      of treating Achilles tendon ruptures.

PMID- 16627631
TI  - Team physicians in college athletics.

PMID- 16627632
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- 16627633
TI  - Notification that new names and new combinations have appeared in volume 56, part
      2, 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- 16627634
TI  - Bacteroides finegoldii sp. nov., isolated from human faeces.
AB  - Two strains, 199T and 176, of Gram-negative, anaerobic, rod-shaped, non-spore
      forming bacteria were isolated during studies of microbiota in human faeces using
      polyamine-deficient medium. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that the isolated strains belonged to the genus Bacteroides.
      The G+C content (42.4-43.0 mol%) and major fatty acid composition (anteiso-C15:0,
      31.8-36.2 %) supported the affiliation of the two strains to the genus
      Bacteroides. 16S rRNA gene sequence similarities with their closest neighbours,
      Bacteroides thetaiotaomicron and Bacteroides ovatus, ranged from 94.6 to 96.5 %.
      DNA-DNA hybridization and phenotypic analysis showed that the two strains
      belonged to the same species (DNA-DNA relatedness of 89 %) and were distinct from
      their close relatives, B. thetaiotaomicron and B. ovatus (<23 % DNA-DNA
      relatedness). On the basis of these data, a novel species of the genus
      Bacteroides, Bacteroides finegoldii sp. nov., is proposed, comprising the
      designated type strain 199T (=JCM 13345T=DSM 17565T) and strain 176 (=JCM 13346).

PMID- 16627635
TI  - Genetic relatedness within the genus Campylobacter inferred from rpoB sequences.
AB  - The genus Campylobacter comprises 17 species, some of which are important animal
      and human pathogens. To gain more insight into the genetic relatedness of this
      genus and to improve the molecular tools available for diagnosis, a universal
      sequencing approach was established for the gene encoding the beta-subunit of RNA
      polymerase (rpoB) for the genus Campylobacter. A total of 59 strains, including
      the type strains of currently recognized species as well as field isolates, were
      investigated in the study. A primer set specific for Campylobacter species
      enabled straightforward amplification and sequencing of a 530 bp fragment of the
      rpoB gene. The 16S rRNA gene sequences of all of the strains were determined in
      parallel. A good congruence was obtained between 16S rRNA and rpoB gene sequence
      based trees within the genus Campylobacter. The branching of the rpoB tree was
      similar to that of the 16S rRNA gene tree, even though a few discrepancies were
      observed for certain species. The resolution of the rpoB gene within the genus
      Campylobacter was generally much higher than that of the 16S rRNA gene sequence,
      resulting in a clear separation of most species and even some subspecies. The
      universally applicable amplification and sequencing approach for partial rpoB
      gene sequence determination provides a powerful tool for DNA sequence-based
      discrimination of Campylobacter species.

PMID- 16627636
TI  - Two novel species, Lysobacter daejeonensis sp. nov. and Lysobacter
      yangpyeongensis sp. nov., isolated from Korean greenhouse soils.
AB  - Two bacterial strains were isolated from greenhouse soils of Daejeon and
      Yangpyeong regions in Korea. The strains, designated GH1-9T and GH19-3T, were
      Gram-negative and aerobic, with rod-shaped cells. Their DNA G+C contents were
      61.7 and 67.3 mol%, respectively. The major fatty acids of strain GH1-9T were iso
      C16 : 0, iso-C15 : 0, iso-C14 : 0, iso-C17 : 1omega9c and iso-C11 : 0 3-OH and
      the major components of strain GH19-3T were iso-C16 : 0, iso-C15 : 0, C16 :
      1omega7c alcohol, iso-C17 : 1omega9c and iso-C11 : 0 3-OH. None of the species of
      the genus Lysobacter with validly published names showed 16S rRNA gene sequence
      similarity values of more than 97 % with respect to the novel isolates. The
      closest sequence similarity of strain GH1-9T was with Lysobacter concretion is
      DSM 16239T (96.4 %), whereas strain GH19-3T showed the highest sequence
      similarity with Lysobacter enzymogenes DSM 2043T (96.6 %). Polyphasic taxonomic
      studies indicated that the two strains should be classified as representing novel
      members of the genus Lysobacter. The names Lysobacter daejeonensis sp. nov. and
      Lysobacter yangpyeongensis sp. nov. are proposed, with strains GH1-9T (=KACC
      11406T=DSM 17634T) and GH19-3T (=KACC 11407T=DSM 17635T), respectively, as the
      type strains.

PMID- 16627637
TI  - Echinicola pacifica gen. nov., sp. nov., a novel flexibacterium isolated from the
      sea urchin Strongylocentrotus intermedius.
AB  - The taxonomic position of three novel marine, heterotrophic, pigmented and
      agarolytic bacteria with gliding motility, isolated from the sea urchin
      Strongylocentrotus intermedius, was investigated. 16S rRNA gene sequence analysis
      revealed that strains KMM 6166, KMM 6172T and KMM 6173 are members of the phylum
      Bacteroidetes; their nearest neighbours were Belliella baltica and Hongiella
      marincola (similarities of 94.5 and 93.6 %, respectively). The DNA G+C content of
      the strains was 44-45 mol%. The predominant fatty acids were C15 : 0 iso,
      C16:1omega5c, C17:1 iso omega9c, C17:0 iso 3-OH and summed feature 3
      (C16:1omega7c and/or C15:0 iso 2-OH). The major respiratory quinone was MK-7.
      Results of molecular experiments supported by phenotypic and chemotaxonomic data
      enabled the isolates to be classified as representatives of a novel species in a
      new genus, for which the name Echinicola pacifica gen. nov., sp. nov. is
      proposed. Echinicola pacifica is the type species of the genus Echinicola, and
      its type strain is KMM 6172T (=KCTC 12368T=LMG 23350T).

PMID- 16627638
TI  - Sandarakinotalea sediminis gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae.
AB  - Four Gram-negative, orange-coloured, aerobic, heterotrophic bacteria were
      isolated from sediment samples collected on the Pacific coast of Japan near the
      cities of Toyohashi and Katsuura. 16S rRNA gene sequence analysis indicated that
      these strains form a distinct lineage within the family Flavobacteriaceae. The
      four isolates shared 99.9-100 % 16S rRNA gene sequence similarity with each other
      and showed 88-90.9 % similarity with their neighbours in the family
      Flavobacteriaceae. The four strains also shared high DNA-DNA reassociation values
      of 67-99 % with each other. All the strains grew at 37 degrees C but not at 4
      degrees C, and degraded gelatin, starch and DNA. The major fatty acids were i
      C15:0, a-C15:0, i-C16:0 and i-C17:0 3-OH. However, two common fatty acids of
      members of the Flavobacteriaceae, i-C15:1 and a-C15:1, were absent in these
      strains. The DNA G+C contents of the four strains were in the range 35-37 mol%.
      On the basis of the polyphasic evidence, it was concluded that these strains
      should be classified as a novel genus and a novel species in the family
      Flavobacteriaceae, for which the name Sandarakinotalea sediminis gen. nov., sp.
      nov. is proposed. The type strain of Sandarakinotalea sediminis is CKA-5T (=NBRC
      100970T=LMG 23247T).

PMID- 16627639
TI  - Ignisphaera aggregans gen. nov., sp. nov., a novel hyperthermophilic
      crenarchaeote isolated from hot springs in Rotorua and Tokaanu, New Zealand.
AB  - Consortia containing a novel coccus-shaped, anaerobic heterotroph together with
      Pyrobaculum rods were cultivated from geothermal environments in New Zealand.
      Pure cultures of the cocci were only obtained from one such consortium, despite
      extensive attempts. Cells of this strain (AQ1.S1T) were regular to irregular
      cocci in morphology and occasionally formed large aggregates, especially when
      utilizing polysaccharides such as konjac glucomannan as a carbon source. Strain
      AQ1.S1T is a hyperthermophile, with an optimal temperature for growth between 92
      and 95 degrees C (range 85-98 degrees C), and a moderate acidophile, with optimal
      growth occurring at pH 6.4 (range 5.4-7.0). Growth was inhibited by the addition
      of sulphur and NaCl (optimal growth occurred without addition of NaCl) and an
      electron acceptor was not required. Strain AQ1.S1T utilized starch, trypticase
      peptone, lactose, glucose, konjac glucomannan, mannose, galactose, maltose,
      glycogen and beta-cyclodextrin as carbon sources. The G+C content was 52.9 mol%.
      Based on 16S rRNA gene sequence analysis and physiological features it is
      proposed that isolate AQ1.S1T (=DSM 17230T=JCM 13409T) represents the type strain
      of a novel species of a new genus within the Crenarchaeota, Ignisphaera aggregans
      gen. nov., sp. nov.

PMID- 16627640
TI  - Cupriavidus pinatubonensis sp. nov. and Cupriavidus laharis sp. nov., novel
      hydrogen-oxidizing, facultatively chemolithotrophic bacteria isolated from
      volcanic mudflow deposits from Mt. Pinatubo in the Philippines.
AB  - Taxonomic studies were performed on ten hydrogen-oxidizing, facultatively
      chemolithotrophic bacteria that were isolated from volcanic mudflow deposits
      derived from the eruption of Mt. Pinatubo in the Philippines in 1991.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that these
      isolates belonged to the genus Cupriavidus of the Betaproteobacteria; sequence
      similarity values with their nearest phylogenetic neighbour, Cupriavidus
      basilensis, were 97.1-98.3 %. In addition to phylogenetic analysis, results of
      whole-cell protein profiles and biochemical tests revealed that these strains
      were members of two distinct species. DNA-DNA hybridizations and whole-cell
      protein profiles enabled these isolates to be differentiated from related
      Cupriavidus species with validly published names. The isolates were aerobic, Gram
      negative, non-sporulating, peritrichously flagellated rods. Their G+C contents
      ranged from 65.2 to 65.9 mol% and their major isoprenoid quinone was ubiquinone Q
      8. On the basis of these results, two novel species are proposed, Cupriavidus
      pinatubonensis sp. nov. [nine strains, with 1245T (=CIP 108725T=PNCM 10346T) as
      the type strain] and Cupriavidus laharis sp. nov. [one strain, the type strain
      1263aT (=CIP 108726T=PNCM 10347T)]. It is also suggested that Ralstonia sp. LMG
      1197 (=JMP 134) should be included in the species C. pinatubonensis.

PMID- 16627641
TI  - Rhodococcus kroppenstedtii sp. nov., a novel actinobacterium isolated from a cold
      desert of the Himalayas, India.
AB  - The taxonomic position of an actinomycete, strain K07-23T, isolated from a cold
      desert of the Himalayas, India, was established by a polyphasic approach. The
      strain exhibited phenotypic characters that were typical of the genus
      Rhodococcus. 16S rRNA gene sequence (1467 bases) comparisons confirmed that
      strain K07-23T belongs to the genus Rhodococcus. 16S rRNA sequence similarity
      studies showed that the isolate is very closely related to Nocardia
      corynebacterioides DSM 20151T (98.6 %), which has been recently reclassified as
      Rhodococcus corynebacterioides. It showed 94.4-96.6 % sequence similarity with
      other species of the genus Rhodococcus. However, genomic relatedness between
      strain K07-23T and R. corynebacterioides as revealed by DNA-DNA hybridization was
      low (62 %). Based on polyphasic analysis, strain K07-23T could be clearly
      distinguished from other species. It is proposed that strain K07-23T (=MTCC
      6634T=DSM 44908T=JCM 13011T) represents a novel species of Rhodococcus,
      Rhodococcus kroppenstedtii sp. nov.

PMID- 16627642
TI  - Methylibium petroleiphilum gen. nov., sp. nov., a novel methyl tert-butyl ether
      degrading methylotroph of the Betaproteobacteria.
AB  - A Gram-negative, rod-shaped, motile, non-pigmented, facultative aerobe that grew
      optimally at pH 6.5 and 30 degrees C (strain PM1T) was isolated for its ability
      to completely degrade the gasoline additive methyl tert-butyl ether. Analysis of
      the 16S rRNA gene sequence indicated that this bacterium was a member of the
      class Betaproteobacteria in the Sphaerotilus-Leptothrix group. The 16S rRNA gene
      sequence identity to other genera in this group, Leptothrix, Aquabacterium,
      Roseateles, Sphaerotilus, Ideonella and Rubrivivax, ranged from 93 to 96 %. The
      chemotaxonomic data including Q-8 as the major quinone, C16 : 1omega7c and C16 :
      0 as the major fatty acids and a DNA G+C content of 69 mol%, support the
      inclusion of strain PM1T in the class Betaproteobacteria. It differed from other
      members of the Sphaerotilus-Leptothrix group by being a facultative methylotroph
      that used methanol as a sole carbon source, and by also being able to grow
      heterotrophically in defined media containing ethanol, toluene, benzene,
      ethylbenzene and dihydroxybenzoates as sole carbon sources. On the basis of the
      morphological, physiological, biochemical and genetic information, a new genus
      and species, Methylibium petroleiphilum gen. nov., sp. nov., is proposed, with
      PM1T (=ATCC BAA-1232T=LMG 22953T) as the type strain.

PMID- 16627643
TI  - Emticicia oligotrophica gen. nov., sp. nov., a new member of the family
      'Flexibacteraceae', phylum Bacteroidetes.
AB  - An aquatic bacterium, strain GPTSA100-15T, was isolated on nutritionally poor
      medium TSBA100 (tryptic soy broth diluted 100 times and solidified with 1.5 %
      agarose) and characterized using a polyphasic approach. The isolate was unable to
      grow on commonly used nutritionally rich media such as tryptic soy agar, nutrient
      agar and Luria-Bertani agar. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that the isolate was affiliated with the family
      'Flexibacteraceae' in the phylum Bacteroidetes. Phylogenetically, it showed
      closest similarity (94.0 %) with an uncultured bacterial clone, HP1A92, detected
      in a sludge microbial community. Among the culturable bacteria, the isolate had
      highest 16S rRNA gene sequence similarity with Leadbetterella byssophila 4M15T
      (87.8 %). Sequence similarities with other members of the phylum Bacteroidetes
      were less than 85 %. The fatty acid profile of the isolate grown on TSBA100
      indicated that the major fatty acid was iso-C15:0, which is also present in many
      members of the family 'Flexibacteraceae'. Cells of strain GPTSA100-15T are Gram
      negative, strictly aerobic rods. The DNA G+C content of the isolate is 36.9 mol%.
      Results of phenotypic, chemotaxonomic and phylogenetic analyses clearly indicate
      that strain GPTSA100-15T represents a new genus within the family
      'Flexibacteraceae'; the name Emticicia gen. nov. is proposed for the genus, with
      Emticicia oligotrophica sp. nov. as the type species. The type strain of
      Emticicia oligotrophica is GPTSA100-15T (=MTCC 6937T=DSM 17448T).

PMID- 16627644
TI  - Flavobacterium soli sp. nov., isolated from soil.
AB  - A Gram-negative, rod-shaped Flavobacterium-like bacterial strain, DS-6T, was
      isolated from soil from the island of Dokdo, Korea, and subjected to a polyphasic
      taxonomic study. Strain DS-6T grew optimally at pH 7.0 and 25 degrees C in the
      presence of 0-0.5 % (w/v) NaCl. It contained MK-6 as the predominant menaquinone
      and iso-C15:0 and iso-C17:0 3-OH as the major fatty acids. The DNA G+C content
      was 36.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated
      that strain DS-6T belonged to the genus Flavobacterium. Levels of 16S rRNA gene
      sequence similarity between strain DS-6T and the type strains of Flavobacterium
      species were below 95.4 %. Strain DS-6T differed from some phylogenetically
      related Flavobacterium species in several phenotypic characteristics. On the
      basis of phenotypic and phylogenetic distinctiveness, DS-6T (=KCTC 12542T=CIP
      108840T) was classified in the genus Flavobacterium as the type strain of a novel
      species, for which the name Flavobacterium soli sp. nov. is proposed.

PMID- 16627645
TI  - Psychromonas ingrahamii sp. nov., a novel gas vacuolate, psychrophilic bacterium
      isolated from Arctic polar sea ice.
AB  - A gas vacuolate bacterium, designated strain 37T, was isolated from a sea ice
      core collected from Point Barrow, Alaska, USA. Cells of strain 37T were large (6
      14 microm in length), rod-shaped, contained gas vacuoles of two distinct
      morphologies, and grew well at NaCl concentrations of 1-10 % and at temperatures
      of -12 to 10 degrees C. The DNA G+C content was 40 mol%. Whole-cell fatty acid
      analysis showed that 16 : 1omega7c comprised 67 % of the total fatty acid
      content. Phylogenetic analysis of 16S rRNA gene sequences indicated that this
      bacterium was closely related to members of the genus Psychromonas, with highest
      sequence similarity (96.8 %) to Psychromonas antarctica. Phenotypic analysis
      differentiated strain 37T from P. antarctica on the basis of several
      characteristics, including cell morphology, growth temperature range and the
      ability to hydrolyse polymers. DNA-DNA hybridization experiments revealed a level
      of relatedness of 37 % between strain 37T and P. antarctica, providing further
      support that it represents a distinct species. The name Psychromonas ingrahamii
      sp. nov. is proposed for this novel species. The type strain is 37T (=CCUG
      51855T=CIP 108865T).

PMID- 16627646
TI  - Reclassification of Serpulina intermedia and Serpulina murdochii in the genus
      Brachyspira as Brachyspira intermedia comb. nov. and Brachyspira murdochii comb.
      nov.
AB  - A reassessment was undertaken of published characteristics of the five species of
      anaerobic intestinal spirochaetes in the genus Brachyspira (Brachyspira aalborgi,
      Brachyspira alvinipulli, Brachyspira hyodysenteriae, Brachyspira innocens and
      Brachyspira pilosicoli) and the two species in the genus Serpulina (Serpulina
      intermedia and Serpulina murdochii). Comparisons were made of published
      descriptions, including phenotypic properties, grouping by multilocus enzyme
      electrophoresis, DNA base composition, DNA-DNA relative reassociation values and
      16S rRNA gene sequence similarity. On the basis of extensive similarities between
      all the species, it is proposed to reclassify Serpulina intermedia Stanton et al.
      1997 and Serpulina murdochii Stanton et al. 1997 in the genus Brachyspira, as
      Brachyspira intermedia comb. nov. (type strain ATCC 51140T) and Brachyspira
      murdochii comb. nov. (type strain ATCC 51284T).

PMID- 16627647
TI  - Bradyrhizobia isolated from root nodules of Parasponia (Ulmaceae) do not
      constitute a separate coherent lineage.
AB  - Rhizobial bacteria almost exclusively nodulate members of the families Fabaceae,
      Mimosaceae and Caesalpiniaceae, but are found on a single non-legume taxon,
      Parasponia (Ulmaceae). Based on their host-range, their nitrogen-fixing ability
      and strain competition experiments, bacterial strains isolated from Parasponia
      were thought to constitute a separate lineage that would account for their
      exceptional host affinity. This hypothesis was investigated by focusing on four
      isolates that are representative of the morphological and cultural types of
      Parasponia-nodulating bradyrhizobia. Their evolutionary relationships with other
      rhizobia were analysed using 16S rRNA gene sequences and their nodulation
      properties were explored using the nodA gene as a proxy for host-range
      specificity. Phylogenetic analyses of the 16S rRNA and nodA gene sequences
      revealed that bacterial isolates from Parasponia species are embedded among other
      bradyrhizobia. They did not cluster together in topologies based on the 16S rRNA
      or nodA gene sequences, but were scattered among other bradyrhizobia belonging to
      either the Bradyrhizobium japonicum or the Bradyrhizobium elkanii lineages. These
      data suggest that the ability of some bradyrhizobia to nodulate species of the
      genus Parasponia does not represent a historical relationship that predates the
      relationship between rhizobia and legumes, but is probably a more recent host
      switch for some rhizobia.

PMID- 16627648
TI  - Desulfovibrio alkalitolerans sp. nov., a novel alkalitolerant, sulphate-reducing
      bacterium isolated from district heating water.
AB  - A novel alkalitolerant, sulphate-reducing bacterium (strain RT2T) was isolated
      from alkaline district heating water. Strain RT2T was a motile vibrio (0.5-0.8
      microm wide and 1.4-1.9 microm long) and grew at pH 6.9-9.9 (optimum at pH 9.0
      9.4) and at 16-47 degrees C (optimum at 43 degrees C). The genomic DNA G+C
      content was 64.7 mol%. A limited number of compounds were used as electron donors
      with sulphate as electron acceptor, including lactate, pyruvate, formate and
      hydrogen/acetate. Sulphite and thiosulphate also served as electron acceptors.
      Based on physiological and genotypic properties, the isolate was considered to
      represent a novel species of the genus Desulfovibrio, for which the name
      Desulfovibrio alkalitolerans sp. nov. is proposed. The type strain is RT2T (=DSM
      16529T=JCM 12612T). The strain is the first alkali-tolerant member of the genus
      Desulfovibrio to be described.

PMID- 16627649
TI  - Estimation of prokaryote genomic DNA G+C content by sequencing universally
      conserved genes.
AB  - Determination of the DNA G+C content of prokaryotic genomes using traditional
      methods is time-consuming and results may vary from laboratory to laboratory,
      depending on the technique used. We explored the possibility of extrapolating the
      genomic DNA G+C content of prokaryotes from gene sequences. For this, 127
      universally conserved genes were studied from 50 prokaryotic genomes in the
      Clusters of Orthologous Groups database. Of these, 57 genes were present as a
      single copy in the genomes of 157 different prokaryote species available in
      GenBank. There was a strong correlation [coefficient of determination (r2) >95 %]
      between the DNA G+C contents of 20 genes and their corresponding genomes. For
      each of the 157 prokaryotic genomes studied, the DNA G+C content of the 20 genes
      was used to determine a 'calculated' genome DNA G+C content (CGC) and this value
      was compared with the 'real' genome DNA G+C content (RGC). In order to select the
      most suitable gene for the determination of CGC values, we compared the r2 and
      median mol% difference between CGC and RGC as well as the sensitivity of each
      gene to provide CGC values for prokaryotic genomes that differ by less than 5
      mol% from their RGC. The highly conserved ftsY gene (median size 1144
      nucleotides), a vertically inherited member of the GTPase superfamily, showed the
      highest r2 value of 0.98, the smallest median mol% difference between CGC and RGC
      of 1.06 and a sensitivity of 100 %. Using ftsY DNA G+C content values, the CGC
      values of 100 genomes not included in the calculation of r2 differed by less than
      5 mol% from their RGC values. These data suggest that the genomic DNA G+C content
      of prokaryotes may be estimated easily and reliably from the ftsY gene sequence.

PMID- 16627650
TI  - Phylogenetic study and multiplex PCR-based detection of Burkholderia plantarii,
      Burkholderia glumae and Burkholderia gladioli using gyrB and rpoD sequences.
AB  - In order to develop a detection method for the rice pathogens Burkholderia
      plantarii, Burkholderia glumae and Burkholderia gladioli, the phylogeny of six
      plant-pathogenic Burkholderia species was analysed using the combined nucleotide
      sequences of gyrB and rpoD. B. plantarii, B. glumae and B. gladioli formed tight
      monophyletic branches supported by high bootstrap probabilities. The high
      sequence similarity revealed a close phylogenetic relationship between B. glumae
      and B. plantarii. B. plantarii strains were divided into three subclusters
      comprising rice strains, whereas the single Vanda strain occupied a unique
      position in the phylogenetic tree. The gyrB and rpoD sequences of all B. glumae
      strains examined were highly conserved. In contrast, B. gladioli strains
      demonstrated a far greater sequence diversity, but this diversity did not
      correlate with pathovar, host plant or geographical origin of the strains. A
      multiplex-PCR protocol using specific primers from the gyrB sequences was
      designed that allowed the specific detection and identification of B. plantarii,
      B. glumae and B. gladioli in rice seeds infected with these pathogenic species.

PMID- 16627651
TI  - Sulfobacillus thermotolerans sp. nov., a thermotolerant, chemolithotrophic
      bacterium.
AB  - A thermotolerant, Gram-positive, aerobic, endospore-forming, acidophilic
      bacterium (strain Kr1T) was isolated from the pulp of a gold-containing sulfide
      concentrate processed at 40 degrees C in a gold-recovery plant (Siberia). Cells
      of strain Kr1(T) were straight to slightly curved rods, 0.8-1.2 microm in
      diameter and 1.5-4.5 microm in length. Strain Kr1T formed spherical and oval,
      refractile, subterminally located endospores. The temperature range for growth
      was 20-60 degrees C, with an optimum at 40 degrees C. The pH range for growth on
      medium containing ferrous iron was 1.2-2.4, with an optimum at pH 2.0; the pH
      range for growth on medium containing S0 was 2.0-5.0, with an optimum at pH 2.5.
      Strain Kr1T was mixotrophic, oxidizing ferrous iron, S0, tetrathionate or sulfide
      minerals as energy sources in the presence of 0.02 % yeast extract or other
      organic substrates. The G+C content of the DNA of strain Kr1T was 48.2+/-0.5
      mol%. Strain Kr1T showed a low level of DNA-DNA reassociation with the known
      Sulfobacillus species (11-44 %). 16S rRNA gene sequence analysis revealed that
      Kr1T formed a separate phylogenetic group with a high degree of similarity
      between the nucleotide sequences (98.3-99.6 %) and 100 % bootstrap support within
      the phylogenetic Sulfobacillus cluster. On the basis of its physiological
      properties and the results of phylogenetic analyses, strain Kr1T can be
      affiliated to a novel species of the genus Sulfobacillus, for which the name
      Sulfobacillus thermotolerans sp. nov. is proposed. The type strain is Kr1T (=VKM
      B-2339T=DSM 17362T).

PMID- 16627652
TI  - Azonexus caeni sp. nov., a denitrifying bacterium isolated from sludge of a
      wastewater treatment plant.
AB  - A polyphasic taxonomic study was carried out to determine the taxonomic position
      of a newly isolated denitrifying bacterium, designated Slu-05T, which had been
      isolated from sludge from the main aerobic treatment tanks of a municipal sewage
      treatment plant. Phylogenetic analysis based on comparative 16S rRNA gene
      sequencing indicated that strain Slu-05T was closely related to Azonexus
      fungiphilus LMG 19178T (96.4 % sequence similarity), the sole species in the
      genus Azonexus. Strain Slu-05T comprised Gram-negative, motile, non-spore-forming
      and slightly curved rods. The predominant respiratory lipoquinone was Q-8. The
      major fatty acids were C16:1omega7c, C16:0, C18:1 isomers and C10:0 3-OH. The G+C
      content of the genomic DNA was 65.6 mol%. The results of DNA-DNA hybridization
      (15.6 %) together with phenotypic determination showed that strain Slu-5T could
      be distinguished from A. fungiphilus. Moreover, some phenotypic properties
      concerning enzyme activity, the substrates utilized as carbon sources and growth
      conditions distinguish strain Slu-5T from A. fungiphilus. On the basis of the
      results obtained in this study, Slu-05T (=DSM 17719T=KCTC 12530T=CCBAU 10199T) is
      the type strain of a novel species of Azonexus, for which the name Azonexus caeni
      sp. nov. is proposed.

PMID- 16627653
TI  - Vulcanibacillus modesticaldus gen. nov., sp. nov., a strictly anaerobic, nitrate
      reducing bacterium from deep-sea hydrothermal vents.
AB  - A novel anaerobic, moderately thermophilic, spore-forming bacterium, designated
      strain BRT, was isolated from deep-sea hydrothermal core samples collected at the
      Rainbow vent field on the Mid-Atlantic Ridge (36 degrees 14' N 33 degrees 54' W).
      The cells were found to be rod-shaped, non-motile, Gram-positive and spore
      forming. The organism grew in the temperature range 37-60 degrees C, with an
      optimum at 55 degrees C, and at pH values in the range 6-8.5, with an optimum
      around pH 7. NaCl concentrations for growth were in the range 10-40 g l(-1), with
      an optimum at 20-30 g l(-1). Strain BRT grew chemo-organoheterotrophically with
      carbohydrates, proteinaceous substrates and organic acids with nitrate as
      electron acceptor. The novel isolate was not able to ferment. The G+C content of
      the genomic DNA was 34.5 mol%. Phylogenetic analysis of the 16S rRNA gene
      sequence placed strain BRT in the Bacillaceae within the class 'Bacilli'. On the
      basis of the phenotypic and phylogenetic data, this isolate should be described
      as a member of a novel genus, for which the name Vulcanibacillus gen. nov. is
      proposed. The type species is Vulcanibacillus modesticaldus sp. nov., with the
      type strain BRT (=DSM 14931T=JCM 12998T).

PMID- 16627654
TI  - Psychroserpens mesophilus sp. nov., a mesophilic marine bacterium belonging to
      the family Flavobacteriaceae isolated from a young biofilm.
AB  - A number of marine bacteria isolated from young biofilms were characterized as
      belonging to the family Flavobacteriaceae. The taxonomic characterization of
      strain KOPRI 13649T, which was isolated from an acrylic surface at the seashore
      at Gangneung, Korea, is reported here. The nearly complete 16S rRNA gene sequence
      of strain KOPRI 13649T was determined and was found to have a high level of
      similarity with that of Psychroserpens burtonensis (95.0-95.6 %). In addition,
      phylogenetic analysis and comparison with closely related strains confirmed that
      the strain represented a novel member of the genus Psychroserpens. The major
      respiratory quinone of strain KOPRI 13649T was MK-6 and the DNA G+C content was
      29.8 mol%. The dominant fatty acid methyl esters were i-15 : 0, a-15 : 0, i-16 :
      0, i-15 : 1omega10, 16 : 1omega7 and 15 : 0. Growth was observed at 10-34 degrees
      C (optimum 30 degrees C), at pH 6-9 (optimum 6.5-8.0) and with 0.5-4 % NaCl
      (optimum 1 %). On the basis of the polyphasic taxonomic evidence presented,
      strain KOPRI 13649T (=KCCM 42261T=JCM 13413T) should be classified as the type
      strain of a novel species in the genus Psychroserpens, for which the name
      Psychroserpens mesophilus sp. nov. is proposed.

PMID- 16627655
TI  - Description of Fabibacter halotolerans gen. nov., sp. nov. and Roseivirga
      spongicola sp. nov., and reclassification of [Marinicola] seohaensis as
      Roseivirga seohaensis comb. nov.
AB  - Bacterial strains UST030701-097T and UST030701-084T were isolated from a marine
      sponge in the Bahamas. Both strains were pink-pigmented, Gram-negative, strictly
      aerobic and chemo-organotrophic. Cells of strain UST030701-097T were short,
      curved rods with fast-gliding motility, whereas those of strain UST030701-084T
      were straight rods with a less rapid gliding motion. The two strains had MK-7 as
      the major respiratory quinone and did not produce flexirubin-type pigments. The
      DNA G+C contents of strains UST030701-097T and UST030701-084T were 42.5 and 43.7
      mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the two strains belonged to the family 'Flexibacteraceae' of the
      phylum Bacteroidetes. 16S rRNA gene sequence similarity between strains UST030701
      097T and UST030701-084T was 95.0 %; their closest relative was [Marinicola]
      seohaensis, with 93.3 % and 96.0 % sequence similarity, respectively.
      Phylogenetic tree topology indicated that the two strains belonged to the same
      lineage, but were on separate branches. Whilst strain UST030701-084T and
      [Marinicola] seohaensis were found on one branch, strain UST030701-097T was in
      another branch that had no species with validly published names. Based on the
      polyphasic taxonomic data obtained in the present study, we propose that strain
      UST030701-097T represents a novel genus and that strain UST030701-084T represents
      a novel species in the phylum Bacteroidetes. The genus Fabibacter gen. nov. is
      proposed, with strain UST030701-097T (=NRRL B-41220T=JCM 13334T) as the type
      strain of the type species, Fabibacter halotolerans sp. nov. Strain UST030701
      084T (=NRRL B-41219T=JCM 13337T) is proposed as the type strain of Roseivirga
      spongicola sp. nov. In an earlier study, it was suggested that the genus
      Marinicola is a later heterotypic synonym of the genus Roseivirga. However, a
      formal proposal to reclassify [Marinicola] seohaensis, the only member of the
      genus Marinicola, has not yet been made. The results of phylogenetic analyses in
      this study support the reclassification of [Marinicola] seohaensis as Roseivirga
      seohaensis comb. nov.

PMID- 16627656
TI  - Photobacterium halotolerans sp. nov., isolated from Lake Martel in Spain.
AB  - A halotolerant bacterium was isolated from a saline lake located in Mallorca,
      Spain. Cells of the strain, designated MACL01T, were Gram-negative, rod-shaped
      and motile by means of polar flagella. Colonies of strain MACL01T were white to
      cream in TSA medium, turning brown after 7 days of incubation; they were blue in
      thiosulphate/citrate/bile salts/sucrose agar medium. A neighbour-joining
      phylogenetic analysis based on 16S rRNA gene sequences showed that strain MACL01T
      belongs to the genus Photobacterium, in which it forms a distinct lineage
      together with Photobacterium rosenbergii and Photobacterium ganghwense (showing
      96.9 and 96.2 % similarity, respectively). The most closely related taxon
      according to phylogenetic analysis of the rpoA gene is also P. rosenbergii (90 %
      similarity). The recA gene also showed low similarity (83.7, 83.4 and 82.4 %,
      respectively) with respect to those of Vibrio proteolyticus LMG 3772T,
      Photobacterium leiognathii LMG 4228T and P. rosenbergii LMG 22223T. Neighbour
      joining phylogenetic analysis of the rpoA and recA genes confirms that strain
      MACL01T belongs to the genus Photobacterium, forming a branch together with P.
      rosenbergii. Strain MACL01T was able to grow in 0-8 % NaCl. Growth occurred
      between 4 and 37 degrees C (optimum, 28 degrees C) and at pH 5-8.5. Luminescence
      was negative on marine agar. Strain MACL01T was found to be sensitive to the
      vibriostatic agent O/129. It reduced nitrate to nitrite, produced beta
      galactosidase and hydrolysed gelatin, but did not produce arginine dihydrolase,
      indole or acetoin. Strain MACL01T used several carbohydrates and fermented
      glucose, L-arabinose and sucrose. The most abundant fatty acids were summed
      feature 3 (32.6 %; comprising C16 : 1omega7c and/or C15 : 0 iso 2-OH), C16 : 0
      (21.2 %) and C18 : 1omega7c (19.9 %). The G+C content of the genomic DNA was 49.8
      mol%. On the basis of genotypic, phenotypic, chemotaxonomic and phylogenetic
      results, strain MACL01T (=LMG 22194T=CECT 5860T) should be classified as the type
      strain of a novel species of the genus Photobacterium, for which the name
      Photobacterium halotolerans sp. nov. is proposed.

PMID- 16627657
TI  - Bacillus okhensis sp. nov., a halotolerant and alkalitolerant bacterium from an
      Indian saltpan.
AB  - A strictly aerobic, rod-shaped bacterium (0.6-0.8 x2-3 microm), designated strain
      Kh10-101T, was isolated from a saltpan (22 degrees 15' N, 69 degrees 1' E) in the
      vicinity of Port Okha, India. The creamish pigmented colonies of strain Kh10-101T
      were round, flat and translucent with irregular margins and a smooth surface. The
      strain possessed up to three subpolar flagella, and was motile by a corkscrew
      motion. The strain grew optimally at 37 degrees C (temperature growth range 25-40
      degrees C) in a complex glucose-containing medium with 5 % NaCl (NaCl growth
      range 0-10 %) at pH 9 (pH growth range pH 7-10), indicating that it was a
      mesophilic halotolerant alkaliphile. The strain was sensitive to lincomycin,
      meticillin, cefuroxime and cephalexin, but resistant to gentamicin, tetracycline
      and cotrimazine. Spores were not detected and cells were heat sensitive. The
      isolate metabolized a range of carbohydrates and hydrolysed casein, gelatin and
      starch. Growth was not observed on aromatic compounds, Tween 40 or Tween 80.
      Nitrate was not reduced and catalase was produced. Electron microscopic
      examination of thin sections revealed a single thick Gram-positive cell wall. The
      DNA G+C content was 41+/-1 mol%. Phylogenetic analyses of the 16S rRNA gene
      sequence revealed that strain Kh10-101T was a member of the sixth rRNA group of
      the genus Bacillus, which includes alkalitolerant, alkaliphilic and halotolerant
      species. The halotolerant obligate alkaliphile Bacillus krulwichiae is the
      closest relative of strain Kh10-101T (96 % similarity) but a number of phenotypic
      differences suggest that strain Kh10-101T (=JCM 13040T=ATCC BAA-1137T) should be
      designated the type strain of a new species, for which the name Bacillus okhensis
      sp. nov. is proposed.

PMID- 16627658
TI  - Porphyrobacter dokdonensis sp. nov., isolated from sea water.
AB  - A Gram-negative, non-motile, non-spore-forming, slightly halophilic bacterial
      strain, DSW-74T, was isolated from sea water off the island of Dokdo, Korea, and
      its taxonomic position was investigated by a polyphasic study. Strain DSW-74T
      grew optimally at 37 degrees C and in the presence of 2 % (w/v) NaCl. It
      contained Q-10 as the predominant ubiquinone and C17 : 1omega6c and C18 :
      1omega7c as the major fatty acids. Its DNA G+C content was 65.8 mol%.
      Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DSW
      74T was most closely related to Porphyrobacter species. Similarity values between
      the 16S rRNA gene sequence of strain DSW-74T and those of the type strains of
      recognized Porphyrobacter species and of Erythromicrobium ramosum were in the
      range 97.4-98.7 %. Strain DSW-74T exhibited 16S rRNA gene sequence similarity
      values of <97.5 % to recognized Erythrobacter species and the other species used
      in the phylogenetic analysis. DNA-DNA relatedness levels and differential
      phenotypic properties made it possible to categorize strain DSW-74T as
      representing a novel Porphyrobacter species. On the basis of the taxonomic data
      presented, it is proposed that DSW-74T (=KCTC 12395T=DSM 17193T) should be
      classified in the genus Porphyrobacter as the type strain of a novel species,
      Porphyrobacter dokdonensis sp. nov.

PMID- 16627659
TI  - Actinocorallia cavernae sp. nov., isolated from a natural cave in Jeju, Korea.
AB  - A novel actinomycete, strain N3-7T, was isolated from a natural cave in Jeju,
      Republic of Korea, using a dilution method and was subjected to characterization
      using polyphasic taxonomy. A 16S rRNA gene sequence analysis revealed that the
      organism belonged to the phylogenetic cluster of the genus Actinocorallia and was
      most closely related to Actinocorallia glomerata and Actinocorallia longicatena
      (97.6 and 97.5 % similarity, respectively). The main chemotaxonomic properties of
      strain N3-7T, such as the principal amino acid of the peptidoglycan, the
      predominant menaquinone and the polar lipid profile, supported classification in
      the genus Actinocorallia. The organism was readily differentiated from
      Actinocorallia species with validly published names on the basis of a broad range
      of phenotypic properties. Thus the isolate represents a novel species of the
      genus Actinocorallia, for which the name Actinocorallia cavernae sp. nov. is
      proposed. The type strain is strain N3-7T (=JCM 13278T=NRRL B-24429T).

PMID- 16627660
TI  - Five novel species of the genus Nocardiopsis isolated from hypersaline soils and
      emended description of Nocardiopsis salina Li et al. 2004.
AB  - Five novel Nocardiopsis strains isolated from hypersaline soils in China were
      subjected to a polyphasic analysis to determine their taxonomic position. All of
      the novel isolates could grow on agar plates at NaCl concentrations of up to 18 %
      (w/v), with optimum growth at 5-8 %. The DNA G+C contents of the novel strains
      ranged from 67.9 to 73.2 mol%. The morphological and chemotaxonomic
      characteristics of the isolates matched those described for members of the genus
      Nocardiopsis. Based on their 16S rRNA gene sequence analysis, DNA-DNA
      hybridization values and phenotypic characteristics, including the composition of
      cell-wall amino acids and sugars, menaquinones, polar lipids and cellular fatty
      acids, the isolates are proposed as representing five novel species of the genus
      Nocardiopsis. The novel species are proposed as Nocardiopsis gilva sp. nov. [type
      strain YIM 90087T (=KCTC 19006T=CCTCC AA 2040012T=DSM 44841T)], Nocardiopsis
      rosea sp. nov. [type strain YIM 90094T (=KCTC 19007T=CCTCC AA 2040013T=DSM
      44842T), Nocardiopsis rhodophaea sp. nov. [type strain YIM 90096T (=KCTC
      19049T=CCTCC AA 2040014T=DSM 44843T), Nocardiopsis chromatogenes sp. nov. [type
      strain YIM 90109T (=KCTC 19008T=CCTCC AA 2040015T=DSM 44844T) and Nocardiopsis
      baichengensis sp. nov. [type strain YIM 90130T (=KCTC 19009T=CCTCC AA
      2040016T=DSM 44845T). On the basis of the chemotaxonomic data, the description of
      the recently described species Nocardiopsis salina Li et al. 2004 is emended.

PMID- 16627661
TI  - Kribbella karoonensis sp. nov. and Kribbella swartbergensis sp. nov., isolated
      from soil from the Western Cape, South Africa.
AB  - Two novel nocardioform actinomycetes, strains Q41T and HMC25T, were isolated from
      soil samples collected in the Western Cape province, South Africa. Rapid genus
      identification revealed that the isolates belonged to the genus Kribbella (based
      on single-digestion restriction analysis of the 16S rRNA gene sequences with
      MboI, VspI, SphI, SnaBI, SalI and AgeI). Both isolates had ll-diaminopimelic acid
      and glycine in their cell-wall peptidoglycan, and contained mannose and ribose as
      whole-cell sugars. Strain HMC25T is able to grow at 45 degrees C and in the
      presence of NaCl (3 %), cephaloridine (10 microg ml(-1)) and gentamicin sulphate
      (10 microg ml(-1)). Strain Q41T grows in the presence of NaCl (2 %). Neither
      strain was able to grow under anaerobic conditions, whereas Kribbella flavida
      KACC 20248T, Kribbella jejuensis HD9T, Kribbella koreensis KACC 20250T and
      Kribbella sandramycini KACC 20249T exhibited weak but distinct growth under
      anaerobic conditions. Physiological test results and 16S rRNA gene sequence
      analysis allowed Q41T and HMC25T to be distinguished from other members of the
      genus with validly published names. Strains HMC25T (=NRRL B-24426T=DSM 17345T)
      and Q41T (=NRRL B-24425T=DSM 17344T) therefore represent the type strains of
      novel species, for which the names Kribbella swartbergensis sp. nov. and
      Kribbella karoonensis sp. nov., respectively, are proposed.

PMID- 16627662
TI  - Pseudoxanthomonas kalamensis sp. nov., a novel gammaproteobacterium isolated from
      Johnston Atoll, North Pacific Ocean.
AB  - An aerobic, mesophilic bacterium, strain JA40T, was isolated from soil
      contaminated with polycyclic aromatic hydrocarbons and polychlorinated biphenyls
      collected from Johnston Atoll in the North Pacific Ocean. The strain formed
      yellow-pigmented colonies on heterotrophic media. The cells were Gram-negative,
      non-motile, non-sporulating rods. The strain reduced nitrite to nitrous oxide,
      the DNA G+C content was 64 mol% and the dominant fatty acids were 15 : 0 iso, 17
      : 1 iso cis7 and 11 : 0 iso 3-OH. DNA sequencing of 1457 nt of the 16S rRNA gene
      established that JA40T belongs in the genus Pseudoxanthomonas within the
      Xanthomonadaceae branch of the Gammaproteobacteria. Strain JA40T can be
      differentiated from other mesophilic species in the genus on the basis of its
      physiological and biochemical characteristics and distinctive fatty acid profile.
      Thus strain JA40T (=ATCC BAA-1031T=CIP 108476T) is the type strain of a novel
      species of the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas
      kalamensis sp. nov. is proposed.

PMID- 16627663
TI  - Neutrotolerant acidophilic Streptomyces species isolated from acidic soils in
      China: Streptomyces guanduensis sp. nov., Streptomyces paucisporeus sp. nov.,
      Streptomyces rubidus sp. nov. and Streptomyces yanglinensis sp. nov.
AB  - The taxonomic status of six neutrotolerant acidophilic streptomycetes isolated
      from acidic soils in Yunnan Province, China, was established using a polyphasic
      approach. The morphological and chemotaxonomic characteristics revealed that the
      isolates belong to the genus Streptomyces. Almost complete 16S rRNA gene
      sequences of the isolates were determined and aligned with available
      corresponding sequences of representatives of the family Streptomycetaceae;
      phylogenetic trees were inferred using four tree-making algorithms. The isolates
      formed a distinct, albeit heterogeneous, subclade in the Streptomyces 16S rRNA
      gene tree together with the type strain of Streptomyces yeochonensis, but were
      readily distinguishable from the latter using DNA-DNA hybridization and
      phenotypic data. It was evident from the genotypic and phenotypic data that the
      isolates belonged to four novel Streptomyces species, for which the following
      names are proposed: Streptomyces guanduensis sp. nov. (type strain 701T=CGMCC
      4.2022T=JCM 13274T), Streptomyces paucisporeus sp. nov. (type strain 1413T=CGMCC
      4.2025T=JCM 13276T), Streptomyces rubidus sp. nov. (type strain 13c15T=CGMCC
      4.2026T=JCM 13277T) and Streptomyces yanglinensis sp. nov. (type strain
      1307T=CGMCC 4.2023T=JCM 13275T); isolates 317 and 913 belong to this latter
      species.

PMID- 16627664
TI  - Reclassification of [Flavobacterium] ferrugineum as Terrimonas ferruginea gen.
      nov., comb. nov., and description of Terrimonas lutea sp. nov., isolated from
      soil.
AB  - Strain DY(T), which was isolated from garden soil in Japan, was subjected to a
      polyphasic taxonomic study. Sequence analysis of the 16S rRNA gene and the GyrB
      protein revealed that the closest relative of strain DYT was [Flavobacterium]
      ferrugineum Sickles and Shaw 1934, with 94.8 and 90.1 % similarity, respectively.
      The two strains had similar chemotaxonomic characteristics, with menaquinone 7 as
      the major quinone system, 47.2-48.9 mol% DNA G+C content and 15 : 0 iso, 15 : 1
      iso, 17 : 0 iso 3-OH and summed feature 3 as the major fatty acids. Based on
      genotypic and phenotypic characteristics, [Flavobacterium] ferrugineum IAM 15098T
      could be clearly differentiated from other members of the genus Flavobacterium.
      Strain DYT and [Flavobacterium] ferrugineum IAM 15098T could be easily
      distinguished from neighbouring taxa by morphological features (non-motile, non
      gliding and non-filamentous single cells). Therefore, it is proposed that
      [Flavobacterium] ferrugineum IAM 15098T and strain DYT represent two separate
      species of a new genus, Terrimonas gen. nov., with the names Terrimonas
      ferruginea comb. nov. (type species; type strain IAM 15098T=ATCC 13524T) and
      Terrimonas lutea sp. nov. (type strain DYT=IAM 15284T=CCTCC AB205006T),
      respectively.

PMID- 16627665
TI  - Williamsia marianensis sp. nov., a novel actinomycete isolated from the Mariana
      Trench.
AB  - The taxonomic status of an actinomycete isolated from sediment collected from the
      Mariana Trench was established using a combination of genotypic and phenotypic
      data. Isolate MT8T had chemotaxonomic and morphological properties consistent
      with its classification in the genus Williamsia, and formed a distinct phyletic
      line in the 16S rRNA gene tree together with the type strain of Williamsia
      muralis. The isolate was readily distinguished from the latter, and from
      representatives of other Williamsia species, using DNA-DNA relatedness and
      phenotypic criteria. Predominant cellular fatty acids were oleic, palmitic and
      tuberculostearic acids and a hexadecenoic acid. The DNA G+C content was 65.2
      mol%. It is apparent that the isolate belongs to a novel species of Williamsia.
      Strain MT8T (=DSM 44944T=NCIMB 14085T) was thus considered to be the type strain
      of a novel species in the genus Williamsia, for which the name Williamsia
      marianensis sp. nov. is proposed.

PMID- 16627666
TI  - Streptococcus massiliensis sp. nov., isolated from a patient blood culture.
AB  - An unidentified strain of the viridans group of streptococci was isolated from a
      human blood sample. It was distinguished from all other recognized species of the
      Streptococcus sanguinis group by several biochemical characteristics.
      Phylogenetic analysis based on 16S rRNA gene sequence comparisons clustered this
      strain with Streptococcus ferus (mutans group) but phylogenetic analysis based on
      rpoB and sodA gene sequence comparisons included it in the S. sanguinis group.
      The isolate showed 95.4 and 95.2 % 16S rRNA gene sequence similarity to S. ferus
      and S. sanguinis, respectively, confirming it as belonging to a novel taxon, for
      which the name Streptococcus massiliensis sp. nov. is proposed. The type strain
      is 4401825T (=CIP 108498T=CCUG 49690T).

PMID- 16627667
TI  - Desulfuromonas svalbardensis sp. nov. and Desulfuromusa ferrireducens sp. nov.,
      psychrophilic, Fe(III)-reducing bacteria isolated from Arctic sediments,
      Svalbard.
AB  - Two psychrophilic, Gram-negative, rod-shaped, motile bacteria (strains 112T and
      102T) that conserved energy from dissimilatory Fe(III) reduction concomitant with
      acetate oxidation were isolated from permanently cold Arctic marine sediments.
      Both strains grew at temperatures down to -2 degrees C, with respective
      temperature optima of 14 degrees C and 14-17 degrees C for strains 112T and 102T.
      The isolated strains reduced Fe(III) using common fermentation products such as
      acetate, lactate, propionate, formate or hydrogen as electron donors, and they
      also grew with fumarate as the sole substrate. As alternatives to Fe(III), they
      reduced fumarate, S0 and Mn(IV). Based on 16S rRNA gene sequence similarity,
      strain 112T was most closely related to Desulfuromonas acetoxidans (97.0 %) and
      Desulfuromonas thiophila NZ27T (95.5 %), and strain 102T to Malonomonas rubra Gra
      Mal 1T (96.3 %) and Desulfuromusa succinoxidans GylacT (95.9 %) within the
      Deltaproteobacteria. Strains 112T and 102T therefore represent novel species, for
      which the names Desulfuromonas svalbardensis sp. nov. (type strain 112T=DSM
      16958T=JCM 12927T) and Desulfuromusa ferrireducens sp. nov. (type strain 102T=DSM
      16956T=JCM 12926T) are proposed.

PMID- 16627668
TI  - A new subclade of haplontic Metschnikowia species associated with insects of
      morning glory flowers in Africa and description of Metschnikowia aberdeeniae sp.
      nov.
AB  - The novel species Metschnikowia aberdeeniae is described to accommodate five
      isolates recovered from insects of morning glory flowers in the Serengeti
      National Park, Tanzania. On the basis of rDNA ITS and D1/D2 large-subunit
      sequences, these yeasts form, together with six other isolates, a novel subclade
      of large-spored Metschnikowia species. The exact position of the subclade within
      the Metschnikowiaceae cannot be determined with any confidence from these
      sequences or from small-subunit rDNA sequences, as the variable sites of the
      sequences are excessively divergent. However, in morphological and physiological
      terms, the novel isolates are typical of the genus Metschnikowia in general and
      of the large-spored group in particular. The type strain of Metschnikowia
      aberdeeniae sp. nov. is strain SUB 05-213.1T (=CBS 10289T=NRRL Y-27921T) (h-) and
      the allotype is strain SUB 05-213.2 (=CBS 10290=NRRL Y-27922) (h+).

PMID- 16627669
TI  - Candida heliconiae sp. nov., Candida picinguabensis sp. nov. and Candida
      saopaulonensis sp. nov., three ascomycetous yeasts from Heliconia velloziana
      (Heliconiaceae).
AB  - Strains belonging to three novel yeast species, Candida heliconiae (four
      isolates), Candida picinguabensis (three isolates) and Candida saopaulonensis
      (two isolates), were recovered in the year 2000 from water of flower bracts of
      Heliconia velloziana L. Emigd. (Heliconiaceae) found in a forest ecosystem site
      in an Atlantic rainforest of south-eastern Brazil. C. picinguabensis and C.
      saopaulonensis were nearly identical in morphology and physiology, but sequence
      divergence in the D1/D2 domain of the large-subunit rDNA indicated that they
      should be regarded as different species. They belong to the Metschnikowiaceae
      clade. C. heliconiae had affinities to Pichia mexicana and related species, but
      was genetically isolated from all currently accepted species in that group. The
      type strains are C. heliconiae UNESP 00-91C1T (=CBS 10000T=NRRL Y-27813T), C.
      picinguabensis UNESP 00-89T (=CBS 9999T=NRRL Y-27814T) and C. saopaulonensis
      UNESP 00-99T (=CBS 10001T=NRRL Y-27815T).

PMID- 16627670
TI  - Candida tibetensis sp. nov. and Candida linzhiensis sp. nov., novel anamorphic,
      ascomycetous yeast species from Tibet.
AB  - Three anamorphic, ascomycetous yeast strains isolated from plant samples
      collected in Linzhi District, Tibet, China, were revealed as representing two
      novel species by 26S rRNA gene D1/D2 domain sequence and physiological property
      comparisons. The names Candida tibetensis sp. nov. and Candida linzhiensis sp.
      nov. are proposed for these novel species, with XZ 41-6T (=AS 2.3072T=CBS 10298T)
      and XZ 92-1T (=AS 2.3073T=CBS 10299T) as the respective type strains. D1/D2
      sequence analysis showed that C. tibetensis and C. linzhiensis are closely
      related to Candida caryicola and Candida sequanensis, respectively.

PMID- 16627671
TI  - Phylogenetic placement of Hanseniaspora-Kloeckera species using multigene
      sequence analysis with taxonomic implications: descriptions of Hanseniaspora
      pseudoguilliermondii sp. nov. and Hanseniaspora occidentalis var. citrica var.
      nov.
AB  - Two protein-coding genes, actin and translation elongation factor-1alpha (EF
      1alpha), as well as two ribosomal gene regions, D1/D2 domains of the large
      subunit and both internal transcribed spacers including the 5.8S gene region,
      were evaluated regarding their usefulness for reconstruction of phylogenetic
      relationships in the Hanseniaspora-Kloeckera species group. This included
      analyses of sequence divergence values, heterogeneity of evolutionary rates and
      the reliability of the inferred trees. Both protein-coding genes showed greater
      capacities to resolve at the strain level and between the closely related species
      of Hanseniaspora-Kloeckera, compared with the ribosomal gene regions. However, to
      obtain a fully resolved and reliable phylogenetic tree that reflected the
      biological relationships it was necessary to combine three congruent sequence
      datasets. The novel species Hanseniaspora pseudoguilliermondii sp. nov. (type
      strain CBS 8772T) is described as a result of the application of various
      molecular approaches to delimit species. Furthermore, incongruent gene
      genealogies of genetically divergent strains of Hanseniaspora occidentalis, as
      determined by amplified fragment length polymorphism analysis and DNA-DNA
      reassociation measurements, indicated the presence of two novel varieties, H.
      occidentalis var. occidentalis (type strain CBS 2592T) and H. occidentalis var.
      citrica var. nov. (type strain CBS 6783T), which could be distinguished by
      habitat preference.

PMID- 16627672
TI  - Effect of smoke inhalation on viscoelastic properties and ventilation
      distribution in sheep.
AB  - Smoke inhalation injuries are the leading cause of mortality from burn injury.
      Airway obstruction due to mucus plugging and bronchoconstriction can cause severe
      ventilation inhomogeneity and worsen hypoxia. Studies describing changes of
      viscoelastic characteristics of the lung after smoke inhalation are missing. We
      present results of a new smoke inhalation device in sheep and describe
      pathophysiological changes after smoke exposure. Fifteen female Merino ewes were
      anesthetized and intubated. Baseline data using electrical impedance tomography
      and multiple-breath inert-gas washout were obtained by measuring ventilation
      distribution, functional residual capacity, lung clearance index, dynamic
      compliance, and stress index. Ten sheep were exposed to standardized cotton smoke
      insufflations and five sheep to sham smoke insufflations. Measured
      carboxyhemoglobin before inhalation was 3.87 +/- 0.28% and 5 min after smoke was
      61.5 +/- 2.1%, range 50-69.4% (P < 0.001). Two hours after smoke functional
      residual capacity decreased from 1,773 +/- 226 to 1,006 +/- 129 ml and lung
      clearance index increased from 10.4 +/- 0.4 to 14.2 +/- 0.9. Dynamic compliance
      decreased from 56.6 +/- 5.5 to 32.8 +/- 3.2 ml/cmH(2)O. Stress index increased
      from 0.994 +/- 0.009 to 1.081 +/- 0.011 (P < 0.01) (all means +/- SE, P < 0.05).
      Electrical impedance tomography showed a shift of ventilation from the dependent
      to the independent lung after smoke exposure. No significant change was seen in
      the sham group. Smoke inhalation caused immediate onset in pulmonary dysfunction
      and significant ventilation inhomogeneity. The smoke inhalation device as
      presented may be useful for interventional studies.

PMID- 16627673
TI  - Increased propensity for apnea in response to acute elevations in left atrial
      pressure during sleep in the dog.
AB  - Periodic breathing is commonly observed in chronic heart failure (CHF) when
      pulmonary capillary wedge pressure is abnormally high and there is usually
      concomitant tachypneic hyperventilation. We hypothesized that acute pulmonary
      hypertension at pressures encountered in CHF and involving all of the lungs and
      pulmonary vessels would predispose to apnea/unstable breathing during sleep. We
      tested this in a chronically instrumented, unanesthetized dog model during non
      rapid eye movement (NREM) sleep. Pulmonary hypertension was created by partial
      occlusion of the left atrium by means of an implanted balloon catheter in the
      atrial lumen. Raising mean left atrial pressure by 5.7 +/- 1.1 Torr resulted
      immediately in tachypneic hyperventilation [breathing frequency increased
      significantly from 13.8 to 19.9 breaths/min; end-tidal P(CO2) (P(ET(CO2))) fell
      significantly from 38.5 to 35.9 Torr]. This tachypneic hyperventilation was
      present during wakefulness, NREM sleep, and rapid eye movement sleep. In NREM
      sleep, this increase in left atrial pressure increased the gain of the
      ventilatory response to CO2 below eupnea (1.3 to 2.2 l.min(-1).Torr(-1)) and
      thereby narrowed the CO2 reserve [P(ET(CO2)) (apneic threshold) - P(ET(CO2))
      (eupnea)], despite the decreased plant gain resulting from the hyperventilation.
      We conclude that acute pulmonary hypertension during sleep results in a narrowed
      CO2 reserve and thus predisposes toward apnea/unstable breathing and may,
      therefore, contribute to the breathing instability observed in CHF.

PMID- 16627674
TI  - Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in
      guinea pigs.
AB  - A lowered threshold to the cough response frequently accompanies chronic airway
      inflammatory conditions. However, the mechanism(s) that from chronic inflammation
      results in a lowered cough threshold is poorly understood. Irritant agents,
      including capsaicin, resiniferatoxin, and citric acid, elicit cough in humans and
      in experimental animals through the activation of the transient receptor
      potential vanilloid 1 (TRPV1). Protease-activated receptor-2 (PAR2) activation
      plays a role in inflammation and sensitizes TRPV1 in cultured sensory neurons by
      a PKC-dependent pathway. Here, we have investigated whether PAR2 activation
      exaggerates TRPV1-dependent cough in guinea pigs and whether protein kinases are
      involved in the PAR2-induced cough modulation. Aerosolized PAR2 agonists (PAR2
      activating peptide and trypsin) did not produce any cough per se. However, they
      potentiated citric acid- and resiniferatoxin-induced cough, an effect that was
      completely prevented by the TRPV1 receptor antagonist capsazepine. In contrast,
      cough induced by hypertonic saline, a stimulus that provokes cough in a TRPV1
      independent manner, was not modified by aerosolized PAR2 agonists. The PKC
      inhibitor GF-109203X, the PKA inhibitor H-89, and the cyclooxygenase inhibitor
      indomethacin did not affect cough induced by TRPV1 agonists, but abated the
      exaggeration of this response produced by PAR2 agonists. In conclusion, PAR2
      stimulation exaggerates TRPV1-dependent cough by activation of diverse
      mechanism(s), including PKC, PKA, and prostanoid release. PAR2 activation, by
      sensitizing TRPV1 in primary sensory neurons, may play a role in the exaggerated
      cough observed in certain airways inflammatory diseases such as asthma and
      chronic obstructive pulmonary disease.

PMID- 16627675
TI  - Effects of chronic NaHCO3 ingestion during interval training on changes to muscle
      buffer capacity, metabolism, and short-term endurance performance.
AB  - This study determined the effects of altering the H(+) concentration during
      interval training, by ingesting NaHCO(3) (Alk-T) or a placebo (Pla-T), on changes
      in muscle buffer capacity (beta m), endurance performance, and muscle
      metabolites. Pre- and posttraining peak O(2) uptake (V(O2 peak)), lactate
      threshold (LT), and time to fatigue at 100% pretraining V(O2 peak) intensity were
      assessed in 16 recreationally active women. Subjects were matched on the LT, were
      randomly placed into the Alk-T (n = 8) or Pla-T (n = 8) groups, and performed 8
      wk (3 days/wk) of six to twelve 2-min cycle intervals at 140-170% of their LT,
      ingesting NaHCO(3) or a placebo before each training session (work matched
      between groups). Both groups had improvements in beta m (19 vs. 9%; P < 0.05) and
      V(O2 peak) (22 vs. 17%; P < 0.05) after the training period, with no differences
      between groups. There was a significant correlation between pretraining beta m
      and percent change in beta m (r = -0.70, P < 0.05). There were greater
      improvements in both the LT (26 vs. 15%; P = 0.05) and time to fatigue (164 vs.
      123%; P = 0.05) after Alk-T, compared with Pla-T. There were no changes to pre-
      or postexercise ATP, phosphocreatine, creatine, and intracellular lactate
      concentrations, or pH(i) after training. Our findings suggest that training
      intensity, rather than the accumulation of H(+) during training, may be more
      important to improvements in beta m. The group ingesting NaHCO(3) before each
      training session had larger improvements in the LT and endurance performance,
      possibly because of a reduced metabolic acidosis during training and a greater
      improvement in muscle oxidative capacity.

PMID- 16627676
TI  - Heat shock protein 72 overexpression protects against hyperthermia, circulatory
      shock, and cerebral ischemia during heatstroke.
AB  - This study extends our earlier studies in rats by applying our heatstroke model
      to a new species. Additionally, transgenic mice are used to examine the role of
      heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were
      heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate
      controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR)
      under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees
      C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial
      pressure, the striatal blood flow, and the striatal PO2 after the onset of
      heatstroke were significantly lower than those in preheat controls. The core and
      brain temperatures, the extracellular concentrations of ischemic and injury
      markers in the striatum, and the striatal neuronal damage scores were
      significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the
      body temperatures, cell ischemia content, and injury marker in the striatum were
      significantly higher, and the mean arterial pressure, striatal blood flow, and
      striatal PO2 concentration were significantly lower during heatstroke than in
      [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72
      significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that
      the overexpression of HSP72 in multiple organs improves survival during
      heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and
      damage in mice.

PMID- 16627677
TI  - Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle fatigue induced by
      electrical stimulation in rats.
AB  - We investigated whether low-level laser therapy (LLLT) can reduce muscular
      fatigue during tetanic contractions in rats. Thirty-two male Wistar rats were
      divided into four groups receiving either one of three different LLLT doses (0.5,
      1.0, and 2.5 J/cm2) or a no-treatment control group. Electrical stimulation was
      used to induce six tetanic muscle contractions in the tibial anterior muscle.
      Contractions were stopped when the muscle force fell to 50% of the initial value
      for each contraction (T50%). There was no significant difference between the 2.5
      J/cm2 laser-irradiated group and the control group in mean T50% values. Laser
      irradiated groups (0.5 and 1.0 J/cm2) had significantly longer T50% values than
      the control group. The relative peak force for the sixth contraction in the laser
      irradiated groups were significantly higher at 92.2% (SD 12.6) for 0.5 J/cm2,
      83.2% (SD 20.5) for 1.0 J/cm2, and 82.9% (SD 18.3) for 2.5 J/cm2 than for the
      control group [50% (SD 15)]. Laser groups receiving 0.5 and 1.0 J/cm2 showed
      significant increases in mean performed work compared with both the control group
      and their first contraction values. Muscle damage was indirectly measured by
      creatine kinase levels in plasma. A distinct dose-response pattern was found in
      which 1.0 and 2.5 J/cm2 LLLT groups had significantly lower creatine kinase
      levels than the 0.5 J/cm2 LLLT group and the control group. We conclude that LLLT
      doses of 0.5 and 1.0 J/cm2 can prevent development of muscular fatigue in rats
      during repeated tetanic contractions.

PMID- 16627678
TI  - IL-1beta decreases the elastic modulus of human tenocytes.
AB  - Cellular responses to mechanical stimuli are regulated by interactions with the
      extracellular matrix, which, in turn, are strongly influenced by the degree of
      cell stiffness (Young's modulus). It was hypothesized that a more elastic cell
      could better withstand the rigors of remodeling and mechanical loading. It was
      further hypothesized that interleukin-1beta (IL-1beta) would modulate
      intracellular cytoskeleton polymerization and regulate cell stiffness. The
      purpose of this study was to investigate the utility of IL-1beta to alter the
      Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to
      the strain, E = stress/strain = (F/A)/(deltaL/L0), where L0 is the equilibrium
      length, deltaL is the length change under the applied stress, F is the force
      applied, and A is the area over which the force is applied. Human tenocytes were
      incubated with 100 pM recombinant human IL-1beta for 5 days. The Young's modulus
      was reduced by 27-63%. Actin filaments were disrupted in >75% of IL-1beta-treated
      cells, resulting in a stellate shape. In contrast, immunostaining of alpha
      tubulin showed increased intensity in IL-1beta-treated tenocytes. Human tenocytes
      in IL-1beta-treated bioartificial tendons were more tolerant to mechanical
      loading than were untreated counterparts. These results indicate that IL-1beta
      reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton
      and/or downregulating the expression of actin and upregulating the expression of
      tubulins. The reduction in cell modulus may help cells to survive excessive
      mechanical loading that may occur in damaged or healing tendons.

PMID- 16627679
TI  - Endothelium-dependent vasodilation of cerebral arteries is altered with simulated
      microgravity through nitric oxide synthase and EDHF mechanisms.
AB  - Cephalic elevations in arterial pressure associated with microgravity and
      prolonged bed rest alter cerebrovascular autoregulation in humans. Using the head
      down tail-suspended (HDT) rat to chronically induce headward fluid shifts and
      elevate cerebral artery pressure, previous work has likewise shown cerebral
      perfusion to be diminished. The purpose of this study was to test the hypothesis
      that 2 wk of HDT reduces cerebral artery vasodilation. To test this hypothesis,
      dose-response relations for endothelium-dependent (2-methylthioadenosine
      triphosphate and bradykinin) and endothelium-independent (nitroprusside)
      vasodilation were determined in vitro in middle cerebral arteries (MCAs) from HDT
      and control rats. All in vitro measurements were done in the presence and absence
      of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (10(-5)
      M) and cyclooxygenase inhibitor indomethacin (10(-5) M). MCA caveolin-1 protein
      content was measured by immunoblot analysis. Endothelium-dependent vasodilation
      to 2-methylthioadenosine triphosphate and bradykinin were both lower in MCAs from
      HDT rats. These lower vasodilator responses were abolished with N(G)-nitro-L
      arginine methyl ester but were unaffected by indomethacin. In addition, HDT was
      associated with lower levels of MCA caveolin-1 protein. Endothelium-independent
      vasodilation was not altered by HDT. These results indicate that chronic cephalic
      fluid shifts diminish endothelium-dependent vasodilation through alterations in
      the endothelial nitric oxide synthase signaling mechanism. Such decrements in
      endothelium-dependent vasodilation of cerebral arteries could contribute to the
      elevations in cerebral vascular resistance and reductions in cerebral perfusion
      that occur after conditions of simulated microgravity in HDT rats.

PMID- 16627680
TI  - Wide-pulse-width, high-frequency neuromuscular stimulation: implications for
      functional electrical stimulation.
AB  - Electrical stimulation (1-ms pulses, 100 Hz) produces more torque than expected
      from motor axon activation (extra contractions). This experiment investigates the
      most effective method of delivering this stimulation for neuromuscular electrical
      stimulation. Surface stimulation (1-ms pulses; 20 Hz for 2 s, 100 Hz for 2 s, 20
      Hz for 3 s) was delivered to triceps surae and wrist flexors (muscle stimulation)
      and to median and tibial nerves (nerve stimulation) at two intensities.
      Contractions were evaluated for amplitude, consistency, and stability. Surface
      electromyograph was collected to assess how H-reflexes and M-waves contribute. In
      the triceps surae, muscle stimulation produced the largest absolute contractions
      (23% maximal voluntary contraction), evoked the largest extra contractions as
      torque increased by 412% after the 100-Hz stimulation, and was more consistent
      and stable compared with tibial nerve stimulation. Absolute and extra contraction
      amplitude, consistency, and stability of evoked wrist flexor torques were similar
      between stimulation types: torques reached 11% maximal voluntary contraction, and
      extra contractions increased torque by 161%. Extra contractions were 10 times
      larger in plantar flexors compared with wrist flexors with muscle stimulation but
      were similar with nerve stimulation. For triceps surae, H reflexes were 3.4 times
      larger than M waves during nerve stimulation, yet M waves were 15 times larger
      than H reflexes during muscle stimulation. M waves in the wrist flexors were
      larger than H reflexes during nerve (8.5 times) and muscle (18.5 times)
      stimulation. This is an initial step toward utilizing extra contractions for
      neuromuscular electrical stimulation and the first to demonstrate their presence
      in the wrist flexors.

PMID- 16627681
TI  - Comparison of lung sound transducers using a bioacoustic transducer testing
      system.
AB  - Sensors used for lung sound research are generally designed by the investigators
      or adapted from devices used in related fields. Their relative characteristics
      have never been defined. We employed an artificial chest wall with a viscoelastic
      surface and a white noise signal generator as a stable source of sound to compare
      the frequency response and pulse waveform reproduction of a selection of devices
      used for lung sound research. We used spectral estimation techniques to determine
      frequency response and cross-correlation of pulses to determine pulse shape
      fidelity. The sensors evaluated were the Siemens EMT 25 C accelerometer
      (Siemens); PPG 201 accelerometer (PPG); Sony ECM-T150 electret condenser
      microphone with air coupler (air coupler; with cylindrical air chambers of 5-, 10
      , and 15-mm diameter and conical air chamber of 10-mm diameter); Littman classic
      stethoscope head (Littman) connected to an electret condenser microphone; and the
      Andries Tek (Andries) electronic stethoscope. We found that the size and shape of
      the air coupler chamber to have no important effect on the detected sound. The
      Siemens, air coupler, and Littman performed similarly with relatively flat
      frequency responses from 200 to 1,200 Hz. The PPG had the broadest frequency
      response, with useful sensitivity extending to 4,000 Hz. The Andries' frequency
      response was the poorest above 1,000 Hz. Accuracy in reproducing pulses roughly
      corresponded with the high-frequency sensitivity of the sensors. We conclude that
      there are important differences among commonly used lung sound sensors that have
      to be defined to allow the comparison of data from different laboratories.

PMID- 16627682
TI  - Mediator mechanisms involved in TRPV1 and P2X receptor-mediated, ROS-evoked
      bradypneic reflex in anesthetized rats.
AB  - Inhalation of H2O2 is known to evoke bradypnea followed by tachypnea, which are
      reflexes resulting from stimulation by reactive oxygen species of vagal lung
      capsaicin-sensitive and myelinated afferents, respectively. This study
      investigated the pharmacological receptors and chemical mediators involved in
      triggering these responses. The ventilatory responses to 0.2% aerosolized H2O2
      were studied before and after various pharmacological pretreatments in
      anesthetized rats. The initial bradypneic response was reduced by a transient
      receptor potential vanilloid 1 (TRPV1) receptor antagonist [capsazepine; change
      (Delta) = -53%] or a P2X purinoceptor antagonist [iso-pyridoxalphosphate-6
      azophenyl-2',5'-disulphonate (PPADS); Delta = -47%] and was further reduced by
      capsazepine and iso-PPADS in combination (Delta = -78%). The initial bradypneic
      response was reduced by a cyclooxygenase inhibitor (indomethacin; Delta = -48%),
      ATP scavengers (apyrase and adenosine deaminase in combination; Delta = -50%), or
      capsazepine and indomethacin in combination (Delta = -47%), was further reduced
      by iso-PPADS and indomethacin in combination (Delta = -75%) or capsazepine and
      ATP scavengers in combination (Delta = -83%), but was not affected by a
      lipoxygenase inhibitor (nordihydroguaiaretic acid) or by any of the various
      vehicles. No pretreatment influenced delayed tachypnea. We concluded that 1) the
      initial bradypneic response to H2O2 results from activation of both TRPV1 and P2X
      receptors, possibly located at terminals of vagal lung capsaicin-sensitive
      afferent fibers; 2) the functioning of the TRPV1 and P2X receptors in triggering
      the initial bradypnea is, in part, mediated through the actions of cyclooxygenase
      metabolites and ATP, respectively; and 3) these mechanisms do not contribute to
      the H2O2-evoked delayed tachypnea.

PMID- 16627683
TI  - Na+-K+-2Cl- cotransporters and Cl- channels regulate citric acid cough in guinea
      pigs.
AB  - Loop diuretics have been shown to inhibit cough and other airway defensive
      reflexes via poorly defined mechanisms. We test the hypothesis that the
      furosemide-sensitive Na+-K+-2Cl- cotransporter (NKCC1) is expressed by sensory
      nerve fibers innervating the airways where it plays an important role in
      regulating sensory neural activity. NKCC1 immunoreactivity was present on the
      cell membranes of most nodose and jugular ganglia neurons projecting to the
      trachea, and it was present on the peripheral terminals of putative
      mechanosensory nerve fibers in the airways. In urethane-anesthetized,
      spontaneously breathing guinea pigs, bolus application of citric acid (1 mM to 2
      M) to an isolated and perfused segment of the tracheal mucosa evoked coughing and
      respiratory slowing. Removal of Cl- from the tracheal perfusate evoked
      spontaneous coughing and significantly potentiated cough and respiratory slowing
      reflexes evoked by citric acid. The NKCC1 inhibitor furosemide (10-100 microM)
      significantly reduced both the number of coughs evoked by citric acid and the
      degree of acid-evoked respiratory slowing (P < 0.05). Localized tracheal
      pretreatment with the Cl- channel inhibitors DIDS or niflumic acid (100 microM)
      also significantly reduced cough, whereas the GABAA receptor agonist muscimol
      potentiated acid-evoked responses. These data suggest that vagal sensory neurons
      may accumulate Cl- due to the expression of the furosemide-sensitive Cl-
      transporter, NKCC1. Efflux of intracellular Cl-, in part through calcium
      activated Cl- channels, may play an important role in regulating airway afferent
      neuron activity.

PMID- 16627684
TI  - Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment
      into, and isolation of viable engrafted donor cells from, the heart.
AB  - Stem cells offer a promising approach to the treatment of myocardial infarction
      and prevention of heart failure. We have used iron labeling of bone marrow
      stromal cells (BMSCs) to noninvasively track cell location in the infarcted rat
      heart over 16 weeks using cine-magnetic resonance imaging (cine-MRI) and to
      isolate the BMSCs from the grafted hearts using the magnetic properties of the
      donor cells. BMSCs were isolated from rat bone marrow, characterized by flow
      cytometry, transduced with lentiviral vectors expressing green fluorescent
      protein (GFP), and labeled with iron particles. BMSCs were injected into the
      infarct periphery immediately following coronary artery ligation, and rat hearts
      were imaged at 1, 4, 10, and 16 weeks postinfarction. Signal voids caused by the
      iron particles in the BMSCs were detected in all rats at all time points. In
      mildly infarcted hearts, the volume of the signal void decreased over the 16
      weeks, whereas the signal void volume did not decrease significantly in severely
      infarcted hearts. High-resolution three-dimensional magnetic resonance (MR)
      microscopy identified hypointense regions at the same position as in vivo. Donor
      cells containing iron particles and expressing GFP were identified in MR-targeted
      heart sections after magnetic cell separation from digested hearts. In
      conclusion, MRI can be used to track cells labeled with iron particles in damaged
      tissue for at least 16 weeks after injection and to guide tissue sectioning by
      accurately identifying regions of cell engraftment. The magnetic properties of
      the iron-labeled donor cells can be used for their isolation from host tissue to
      enable further characterization.

PMID- 16627685
TI  - The phenotypes of pluripotent human hepatic progenitors.
AB  - Human livers contain two pluripotent hepatic progenitors, hepatic stem cells and
      hepatoblasts, with size, morphology, and gene expression profiles distinct from
      that of mature hepatocytes. Hepatic stem cells, the precursors to hepatoblasts,
      persist in stable numbers throughout life, and those isolated from the livers of
      all age donors from fetal to adult are essentially identical in their gene and
      protein expression profiles. The gene expression profile of hepatic stem cells
      throughout life consists of high levels of expression of cytokeratin 19 (CK19),
      neuronal cell adhesion molecule (NCAM), epithelial cell adhesion molecule
      (EpCAM), and claudin-3 (CLDN-3); low levels of albumin; and a complete absence of
      expression of alpha-fetoprotein (AFP) and adult liver-specific proteins. By
      contrast, hepatoblasts, the dominant cell population in fetal and neonatal
      livers, decline in numbers with age and are found as <0.1% of normal adult
      livers. They express high levels of AFP, elevated levels of albumin, low levels
      of expression of adult liver-specific proteins, low levels of CK19, and a loss of
      NCAM and CLDN-3. Mature hepatocytes lack expression altogether of EpCAM, NCAM,
      AFP, CLDN-3, cytokeratin 19, and have acquired the well-known adult-specific
      profile that includes expression of high levels of albumin, cytochrome P4503A4,
      connexins, phosphoenolpyruvate carboxykinase, and transferrin. Thus, hepatic stem
      cells have a unique stem cell phenotype, whereas hepatoblasts have low levels of
      expression of both stem cell genes and genes expressed in high levels in mature
      hepatocytes.

PMID- 16627686
TI  - Embryonic stem cell-derived neural progenitors display temporal restriction to
      neural patterning.
AB  - Neural stem cells have considerable therapeutic potential because of their
      ability to generate defined neuronal cell types for use in drug screening studies
      or cell-based therapies for neurodegenerative diseases. In this study, we
      differentiate mouse embryonic stem cells to neural progenitors with an initial
      forebrain identity in a defined system that enables systematic manipulation to
      generate more caudal fates, including motoneurons. We demonstrate that the
      ability to pattern embryonic stem cell-derived neural progenitors is temporally
      restricted and show that the loss of responsiveness to morphogenetic cues
      correlates with constitutive expression of the basic helix-loop-helix
      transcription factors Olig2 and Mash1, epidermal growth factor receptor, and
      vimentin and parallels the onset of gliogenesis. We provide evidence for two
      temporal classes of embryonic stem cell-derived putative radial glia that
      coincide with a transition from neurogenesis to gliogenesis and a concomitant
      loss of regional identity.

PMID- 16627687
TI  - Selection of neural differentiation-specific genes by comparing profiles of
      random differentiation.
AB  - Differentiation of embryonic stem cells (ESCs) into neurons requires a high level
      of transcriptional regulation. To further understand the transcriptional
      regulation of neural differentiation of ESCs, we used oligonucleotide microarray
      to examine the gene expressions of the guided differentiation (GD) model for
      dopaminergic (DA) neurons from mouse ESCs. We also determined the gene expression
      profiles of the random differentiation (RD) model of mouse ESCs into embryoid
      bodies. From K-means clustering analysis using the expression patterns of the two
      models, most of the genes (1,282 of 1,884 genes [68.0%]) overlapped in their
      expression patterns. Six hundred twenty-two differentially expressed genes (DEGs)
      from the GD model by random variance F-test were classified by their critical
      molecular functions in neurogenesis and DNA replication (Gene Ontology analysis).
      However, 400 genes among GD-DEGs (64.3%) showed a high correlation with RD in
      Spearman's correlation analysis (Spearman's coefficient p(s) >or= .6). The genes
      showing marginal correlation (-.4 < p(s) < .6) were present in the early stages
      of differentiation of both GD and RD, which were non-specific to brain
      development. Finally, we distinguished 66 GD-specific genes based on p(s) <or= 
      .4, the molecular functions of which were related mainly to vesicle formation,
      neurogenesis, and transcription factors. From among these GD-specific genes, we
      confirmed the expression of Serpini1 and Rab33a in P19 differentiation models and
      adult brains. From these results, we identified the specific genes required for
      neural differentiation by comparing gene expressions of GD with RD; these would
      potentially be the highly specific candidate genes necessary for differentiation
      of DA neurons.

PMID- 16627688
TI  - Long-term facilitation of ventilation and genioglossus muscle activity is evident
      in the presence of elevated levels of carbon dioxide in awake humans.
AB  - We hypothesized that long-term facilitation (LTF) of minute ventilation and peak
      genioglossus muscle activity manifests itself in awake healthy humans when carbon
      dioxide is sustained at elevated levels. Eleven subjects completed two trials.
      During trial 1, baseline carbon dioxide levels were maintained during and after
      exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was
      sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven
      subjects were exposed to sustained elevated levels of carbon dioxide in the
      absence of episodic hypoxia, which served as a control experiment. Minute
      ventilation was measured during trial 1, trial 2, and the control experiment.
      Peak genioglossus muscle activity was measured during trial 2. Minute ventilation
      during the recovery period of trial 1 was similar to baseline (9.3 +/- 0.5 vs.
      9.2 +/- 0.7 l/min). Likewise, minute ventilation remained unchanged during the
      control experiment (beginning vs. end of control experiment, 14.4 +/- 1.7 vs.
      14.7 +/- 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle
      activity during the recovery period of trial 2 was greater than baseline (minute
      ventilation: 28.4 +/- 1.7 vs. 19.6 +/- 1.0 l/min, P < 0.001; peak genioglossus
      activity: 1.6 +/- 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that
      exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and
      peak genioglossus muscle activity and that LTF is only evident in awake humans in
      the presence of sustained elevated levels of carbon dioxide.

PMID- 16627689
TI  - Changes in body temperature in king penguins at sea: the result of fine
      adjustments in peripheral heat loss?
AB  - To investigate thermoregulatory adjustments at sea, body temperatures (the
      pectoral muscle and the brood patch) and diving behavior were monitored during a
      foraging trip of several days at sea in six breeding king penguins Aptenodytes
      patagonicus. During inactive phases at sea (water temperature: 4-7 degrees C),
      all tissues measured were maintained at normothermic temperatures. The brood
      patch temperature was maintained at the same values as those measured when
      brooding on shore (38 degrees C). This high temperature difference causes a
      significant loss of heat. We hypothesize that high-energy expenditure associated
      with elevated peripheral temperature when resting at sea is the thermoregulatory
      cost that a postabsorptive penguin has to face for the restoration of its
      subcutaneous body fat. During diving, mean pectoral temperature was 37.6 +/- 1.6
      degrees C. While being almost normothermic on average, the temperature of the
      pectoral muscle was still significantly lower than during inactivity in five out
      of the six birds and underwent temperature drops of up to 5.5 degrees C. Mean
      brood patch temperature was 29.6 +/- 2.5 degrees C during diving, and temperature
      decreases of up to 21.6 degrees C were recorded. Interestingly, we observed
      episodes of brood patch warming during the descent to depth, suggesting that, in
      some cases, king penguins may perform active thermolysis using the brood patch.
      It is hypothesized that functional pectoral temperature may be regulated through
      peripheral adjustments in blood perfusion. These two paradoxical features, i.e.,
      lower temperature of deep tissues during activity and normothermic peripheral
      tissues while inactive, may highlight the key to the energetics of this diving
      endotherm while foraging at sea.

PMID- 16627690
TI  - Attenuation of homeostatic responses to hypotension and glucoprivation after
      destruction of catecholaminergic rostral ventrolateral medulla neurons.
AB  - This study determined the effect of destruction of rostral ventrolateral medulla
      (RVLM)-C1 cells on integrated sympathetic and hormonal responses to hypotension
      or glucoprivation. Injection of anti-dopamine beta-hydroxylase-saporin into the
      RVLM resulted in 29-99% depletion of RVLM-C1 neurons and approximately 60%
      reduction in the number of A5 neurons. As in our previous study in unanesthetized
      rats, resting mean arterial pressure (MAP) was reduced by approximately 10 mmHg
      in rats with >80% depletion of RVLM-C1 cells compared with control rats, although
      resting heart rate (HR) did not differ significantly. In the present study,
      resting plasma levels of norepinephrine (NE) did not differ significantly between
      control rats and rats with >80% depletion of RVLM-C1 cells, although there was a
      tendency for RVLM-C1 lesioned rats to have lower levels. Also consistent with our
      previous study, hydralazine (HDZ)-evoked hypotension resulted in smaller
      increases in HR and plasma levels of NE in rats with >80% depletion of RVLM-C1
      cells compared with control rats. Furthermore, the elevated plasma levels of
      posterior pituitary hormones vasopressin and oxytocin evoked by HDZ were blunted
      in RVLM-C1 lesioned rats compared with control rats, even though MAP fell to
      lower levels in the lesioned rats. Plasma renin activity, plasma osmolality, and
      plasma protein concentrations did not differ between control rats and rats with
      >80% depletion of RVLM-C1 neurons. In response to systemic administration of 2
      deoxyglucose, the circulating level of epinephrine and the resulting
      hyperglycemia were attenuated in rats with >80% depletion of RVLM-C1 cells
      compared with control rats. These results demonstrate that RVLM-C1 cells, in
      addition to playing a role in acute cardiovascular reflexes, play an important
      role in integrated sympathetic and hormonal responses to homeostatic challenges
      such as hypotension and glucoprivation.

PMID- 16627691
TI  - Increased expression of sFlt-1 in in vivo and in vitro models of human placental
      hypoxia is mediated by HIF-1.
AB  - Elevated expression of soluble vascular endothelial growth factor receptor-1
      (sFlt-1) in preeclampsia plays a major role in the pathogenesis of this serious
      disorder of human pregnancy. Although reduced placental oxygenation is thought to
      be involved in the pathogenesis of preeclampsia, it is unclear how oxygen
      regulates placental sFlt-1 expression. The aims herein were to investigate sFlt-1
      expression in in vivo and in vitro physiological and pathological models of human
      placental hypoxia and to understand the role of hypoxia inducible factor-1 (HIF
      1) in regulating the expression of this molecule. sFlt-1 expression in placental
      villi was significantly increased under physiological low oxygen conditions in
      early first-trimester and in high-altitude placentae, as well as in pathological
      low oxygen conditions, such as preeclampsia. In high-altitude and in preeclamptic
      tissue, sFlt-1 localized within villi to perivascular regions, the
      syncytiotrophoblast layer, and syncytial knots. In first-trimester villous
      explants, low oxygen, but not hypoxia-reoxygenation (HR), increased sFlt-1
      expression. Moreover, exposure of villous explants to dimethyloxalyl-glycin, a
      pharmacological inhibitor of prolyl-hydroxylases, which mimics hypoxia by
      increasing HIF-1alpha stability, increased sFlt-1 expression. Conversely, HIF
      1alpha knockdown using antisense oligonucleotides, decreased sFlt-1 expression.
      In conclusion, placental sFlt-1 expression is increased by both physiologically
      and pathologically low levels of oxygen. This oxygen-induced effect is mediated
      via the transcription factor HIF-1. Low oxygen levels, as opposed to intermittent
      oxygen tension (HR) changes, play an important role in regulating sFlt-1
      expression in the developing human placenta and hence may contribute to the
      development of preeclampsia.

PMID- 16627692
TI  - Free radical biology and medicine: it's a gas, man!
AB  - We review gases that can affect oxidative stress and that themselves may be
      radicals. We discuss O(2) toxicity, invoking superoxide, hydrogen peroxide, and
      the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground
      state, triplet oxygen ((3)O(2)), and the more energetic, reactive singlet oxygen
      ((1)O(2)). Nitric oxide ((*)NO) is a free radical with cell signaling functions.
      Besides its role as a vasorelaxant, (*)NO and related species have other
      functions. Other endogenously produced gases include carbon monoxide (CO), carbon
      dioxide (CO(2)), and hydrogen sulfide (H(2)S). Like (*)NO, these species impact
      free radical biochemistry. The coordinated regulation of these species suggests
      that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the
      carbonate radical (CO(3)(*-)) react selectively at moderate rates with
      nonradicals, but react fast with a second radical. These reactions establish
      "cross talk" between reactive oxygen (ROS) and reactive nitrogen species (RNS).
      Some of these species can react to produce nitrated proteins and nitrolipids. It
      has been suggested that ozone is formed in vivo. However, the biomarkers that
      were used to probe for ozone reactions may be formed by non-ozone-dependent
      reactions. We discuss this fascinating problem in the section on ozone. Very low
      levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative
      stress that can result in growth arrest (transient or permanent), apoptosis, or
      necrosis. Between these extremes, many of the gasses discussed in this review
      will induce transient adaptive responses in gene expression that enable cells and
      tissues to survive. Such adaptive mechanisms are thought to be of evolutionary
      importance.

PMID- 16627694
TI  - Under what conditions is ingested sodium rendered osmotically inactive?

PMID- 16627695
TI  - Placental restriction alters circulating thyroid hormone in the young lamb
      postnatally.
AB  - Intrauterine growth restriction (IUGR) is associated with accelerated growth and
      increased adiposity in early life due to unknown mechanisms, which could include
      increased thyroid hormone (TH) action. We hypothesized that placental restriction
      (PR) of fetal growth would increase circulating TH concentrations and alter their
      response to fasting, and that these would relate to growth and body composition
      in the young lamb. PR reduced size at birth, increased fractional growth rates
      (FGRs) of soft and skeletal tissues up to 30 days of age, and slowed the
      ontogenic decrease in plasma total T3 and plasma total T3/T4. PR did not alter
      the abundance of plasma THs after short-term fasting. In general, plasma total T3
      and total T3/T4 ratio correlated negatively, whereas plasma total T4 correlated
      positively with size at birth. Absolute growth rates of weight and crown-rump
      length correlated positively with plasma total T3 and total T4 between days 15
      and 35. Current FGRs for weight and metatarsal length correlated positively with
      plasma total T3 between days 20 and 35. In conclusion, PR and small size at birth
      reduce plasma total T4 and increase plasma total T3 postnatally, whereas catch-up
      growth relates to increased abundance of the more bioactive forms of TH. Finally,
      greater soft tissue growth occurs in PR compared with control lambs at the same
      circulating TH concentrations. This suggests that PR and small size at birth may
      increase activation of T4 to T3 and sensitivity of soft tissues to TH, which may
      contribute to catch-up growth following IUGR.

PMID- 16627696
TI  - Activation of central opioid receptors determines the timing of hypotension
      during acute hemorrhage-induced hypovolemia in conscious sheep.
AB  - After an initial compensatory phase, hemorrhage reduces blood pressure due to a
      widespread reduction of sympathetic nerve activity (decompensatory phase). Here,
      we investigate the influence of intracerebroventricular naloxone (opioid-receptor
      antagonist) and morphine (opioid-receptor agonist) on the two phases of
      hemorrhage, central and peripheral hemodynamics, and release of vasopressin and
      renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml x
      kg(-1) x min(-1)) from a jugular vein until mean arterial blood pressure (MAP)
      reached 50 mmHg. Starting 30 min before and continuing until 60 min after
      hemorrhage, either artificial cerebrospinal fluid (aCSF), naloxone, or morphine
      was infused intracerebroventricularly. Naloxone (200 microg/min but not 20 or 2.0
      microg/min) significantly increased the hemorrhage volume compared with aCSF
      (19.5 +/- 3.2 vs. 13.9 +/- 1.1 ml/kg). Naloxone also increased heart rate and
      cardiac index. Morphine (2.0 microg/min) increased femoral blood flow and
      decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9 +/- 1.5 vs. 13.9
      +/- 1.1 ml/kg). The effects of morphine were abolished by naloxone at 20
      microg/min. It is concluded that the commencement of the decompensatory phase of
      hemorrhage in conscious sheep involves endogenous activation of central opioid
      receptors. The effective dose of morphine most likely activated mu-opioid
      receptors, but they appear not to have been responsible for initiating
      decompensation as 1) naloxone only inhibited an endogenous mechanism at a dose
      much higher than the effective dose of morphine, and 2) the effects of morphine
      were blocked by a dose of naloxone, which, by itself, did not delay the
      decompensatory phase.

PMID- 16627697
TI  - Visualization of cellulose synthase demonstrates functional association with
      microtubules.
AB  - Expression of a functional yellow fluorescent protein fusion to cellulose
      synthase (CESA) in transgenic Arabidopsis plants allowed the process of cellulose
      deposition to be visualized in living cells. Spinning disk confocal microscopy
      revealed that CESA complexes in the plasma membrane moved at constant rates in
      linear tracks that were aligned and were coincident with cortical microtubules.
      Within each observed linear track, complex movement was bidirectional. Inhibition
      of microtubule polymerization changed the fine-scale distribution and pattern of
      moving CESA complexes in the membrane, indicating a relatively direct mechanism
      for guidance of cellulose deposition by the cytoskeleton.

PMID- 16627698
TI  - Drilling to gabbro in intact ocean crust.
AB  - Sampling an intact sequence of oceanic crust through lavas, dikes, and gabbros is
      necessary to advance the understanding of the formation and evolution of crust
      formed at mid-ocean ridges, but it has been an elusive goal of scientific ocean
      drilling for decades. Recent drilling in the eastern Pacific Ocean in Hole 1256D
      reached gabbro within seismic layer 2, 1157 meters into crust formed at a
      superfast spreading rate. The gabbros are the crystallized melt lenses that
      formed beneath a mid-ocean ridge. The depth at which gabbro was reached confirms
      predictions extrapolated from seismic experiments at modern mid-ocean ridges:
      Melt lenses occur at shallower depths at faster spreading rates. The gabbros
      intrude metamorphosed sheeted dikes and have compositions similar to the
      overlying lavas, precluding formation of the cumulate lower oceanic crust from
      melt lenses so far penetrated by Hole 1256D.

PMID- 16627699
TI  - Flip-flopping fractional flux quanta.
AB  - The d-wave pairing symmetry in high-critical temperature superconductors makes it
      possible to realize superconducting rings with built-in pi phase shifts. Such
      rings have a twofold degenerate ground state that is characterized by the
      spontaneous generation of fractional magnetic flux quanta with either up or down
      polarity. We have incorporated pi phase-biased superconducting rings in a logic
      circuit, a flip-flop, in which the fractional flux polarity is controllably
      toggled by applying single flux quantum pulses at the input channel. The
      integration of p rings into conventional rapid single flux quantum logic as
      natural two-state devices should alleviate the need for bias current lines,
      improve device symmetry, and enhance the operation margins.

PMID- 16627700
TI  - Atomic-scale coupling of photons to single-molecule junctions.
AB  - Spatial resolution at the atomic scale has been achieved in the coupling of light
      to single molecules adsorbed on a surface. Electron transfer to a single molecule
      induced by green to near-infrared light in the junction of a scanning tunneling
      microscope (STM) exhibited spatially varying probability that is confined within
      the molecule. The mechanism involves photo-induced resonant tunneling in which a
      photoexcited electron in the STM tip is transferred to the molecule. The coupling
      of photons to the tunneling process provides a pathway to explore molecular
      dynamics with the combined capabilities of lasers and the STM.

PMID- 16627701
TI  - Early diagnosis of avian influenza.

PMID- 16627702
TI  - Biomedical research. Court decides tissue samples belong to university, not
      patients.

PMID- 16627703
TI  - Women in science. Progress on hiring women science faculty members stalls at MIT.

PMID- 16627704
TI  - Science policy. NSF begins a push to measure societal impacts of research.

PMID- 16627705
TI  - Cosmology. Skewed starlight suggests particle masses changed over eons.

PMID- 16627706
TI  - Development. Gene-suppressing proteins reveal secrets of stem cells.

PMID- 16627707
TI  - Geophysics. Opening the door to a chilly new climate regime.

PMID- 16627708
TI  - Southeast Asia. Thai scientists secure royally inspired windfall.

PMID- 16627709
TI  - Climatology. Latest forecast: stand by for a warmer, but not scorching, world.

PMID- 16627710
TI  - Israel-Palestine science. Bridging the divide in the Holy Land.

PMID- 16627711
TI  - Israel-Palestine science. Palestinian archaeology braces for a storm.

PMID- 16627712
TI  - Israel-Palestine science. Breaking up bomb plots--and habitats?

PMID- 16627713
TI  - Cancer research. After regime change at the National Cancer Institute.

PMID- 16627714
TI  - Meeting briefs. Graves of the Pacific's first seafarers revealed.

PMID- 16627716
TI  - Meeting briefs. Java Man's first tools.

PMID- 16627715
TI  - Meeting briefs. When in Vietnam, build boats as the Romans do.

PMID- 16627722
TI  - Assessing clinical trial results.

PMID- 16627723
TI  - Ethics issues in stem cell research.

PMID- 16627724
TI  - Comment on "Phylogenetic MCMC algorithms are misleading on mixtures of trees".
AB  - Mossel and Vigoda (Reports, 30 September 2005, p. 2207) show that nearest
      neighbor interchange transitions, commonly used in phylogenetic Markov chain
      Monte Carlo (MCMC) algorithms, perform poorly on mixtures of dissimilar trees.
      However, the conditions leading to their results are artificial. Standard MCMC
      convergence diagnostics would detect the problem in real data, and correction of
      the model misspecification would solve it.

PMID- 16627725
TI  - Genetics. No longer de-identified.

PMID- 16627726
TI  - Ecology. Mutualistic webs of species.

PMID- 16627727
TI  - Chemistry. The first femtosecond in the life of a chemical reaction.

PMID- 16627728
TI  - Applied physics. Laser-driven particle accelerators.

PMID- 16627729
TI  - Materials science. Self-assembly of unusual nanoparticle crystals.

PMID- 16627730
TI  - Pharmacology. Hitting the hot spots of cell signaling cascades.

PMID- 16627732
TI  - A one-size-fits-all flu vaccine?

PMID- 16627733
TI  - Oseltamivir becomes plentiful--but still not cheap.

PMID- 16627734
TI  - Global patterns of influenza a virus in wild birds.
AB  - The outbreak of highly pathogenic avian influenza of the H5N1 subtype in Asia,
      which has subsequently spread to Russia, the Middle East, Europe, and Africa, has
      put increased focus on the role of wild birds in the persistence of influenza
      viruses. The ecology, epidemiology, genetics, and evolution of pathogens cannot
      be fully understood without taking into account the ecology of their hosts. Here,
      we review our current knowledge on global patterns of influenza virus infections
      in wild birds, discuss these patterns in the context of host ecology and in
      particular birds' behavior, and identify some important gaps in our current
      knowledge.

PMID- 16627735
TI  - Emergence of drug-resistant influenza virus: population dynamical considerations.
AB  - Given the considerable challenges to the rapid development of an effective
      vaccine against influenza, antiviral agents will play an important role as a
      first-line defense if a new pandemic occurs. The large-scale use of drugs for
      chemoprophylaxis and treatment will impose strong selection for the evolution of
      drug-resistant strains. The ensuing transmission of those strains could
      substantially limit the effectiveness of the drugs as a first-line defense.
      Summarizing recent data on the rate at which the treatment of influenza infection
      generates resistance de novo and on the transmission fitness of resistant virus,
      we discuss possible implications for the epidemiological spread of drug
      resistance in the context of an established population dynamic model.

PMID- 16627736
TI  - Predictability and preparedness in influenza control.
AB  - The threat of pandemic human influenza looms as we survey the ongoing avian
      influenza pandemic and wonder if and when it will jump species. What are the
      risks and how can we plan? The nub of the problem lies in the inherent
      variability of the virus, which makes prediction difficult. However, it is not
      impossible; mathematical models can help determine and quantify critical
      parameters and thresholds in the relationships of those parameters, even if the
      relationships are nonlinear and obscure to simple reasoning. Mathematical models
      can derive estimates for the levels of drug stockpiles needed to buy time, how
      and when to modify vaccines, whom to target with vaccines and drugs, and when to
      enforce quarantine measures. Regardless, the models used for pandemic planning
      must be tested, and for this we must continue to gather data, not just for
      exceptional scenarios but also for seasonal influenza.

PMID- 16627737
TI  - Host species barriers to influenza virus infections.
AB  - Most emerging infectious diseases in humans originate from animal reservoirs; to
      contain and eradicate these diseases we need to understand how and why some
      pathogens become capable of crossing host species barriers. Influenza virus
      illustrates the interaction of factors that limit the transmission and subsequent
      establishment of an infection in a novel host species. Influenza species barriers
      can be categorized into virus-host interactions occurring within individuals and
      host-host interactions, either within or between species, that affect
      transmission between individuals. Viral evolution can help surmount species
      barriers, principally by affecting virus-host interactions; however, evolving the
      capability for sustained transmission in a new host species represents a major
      adaptive challenge because the number of mutations required is often large.

PMID- 16627738
TI  - Global mineralogical and aqueous mars history derived from OMEGA/Mars Express
      data.
AB  - Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie,
      l'Eau, les Glaces et l'Activite (OMEGA) instrument on the European Space Agency's
      Mars Express spacecraft provides new information on Mars' geological and climatic
      history. Phyllosilicates formed by aqueous alteration very early in the planet's
      history (the "phyllocian" era) are found in the oldest terrains; sulfates were
      formed in a second era (the "theiikian" era) in an acidic environment. Beginning
      about 3.5 billion years ago, the last era (the "siderikian") is dominated by the
      formation of anhydrous ferric oxides in a slow superficial weathering, without
      liquid water playing a major role across the planet.

PMID- 16627739
TI  - Bolometric infrared photoresponse of suspended single-walled carbon nanotube
      films.
AB  - The photoresponse in the electrical conductivity of a single-walled carbon
      nanotube (SWNT) film is dramatically enhanced when the nanotube film is suspended
      in vacuum. We show here that the change in conductivity is bolometric (caused by
      heating of the SWNT network). Electron-phonon interactions lead to ultrafast
      relaxation of the photoexcited carriers, and the energy of the incident infrared
      (IR) radiation is efficiently transferred to the crystal lattice. It is not the
      presence of photoexcited holes and electrons, but a rise in temperature, that
      results in a change in resistance; thus, photoconductivity experiments cannot be
      used to support the band picture over the exciton model of excited states in
      carbon nanotubes. The photoresponse of suspended SWNT films is sufficiently high
      that they may function as the sensitive element of an IR bolometric detector.

PMID- 16627740
TI  - Atomic pillar-based nanoprecipitates strengthen AlMgSi alloys.
AB  - Atomic-resolution electron microscopy reveals that pillarlike silicon double
      columns exist in the hardening nanoprecipitates of AlMgSi alloys, which vary in
      structure and composition. Upon annealing, the Si2 pillars provide the skeleton
      for the nanoparticles to evolve in composition, structure, and morphology. We
      show that they begin as tiny nuclei with a composition close to Mg2Si2Al7 and a
      minimal mismatch with the aluminum matrix. They subsequently undergo a one
      dimensional growth in association with compositional change, becoming elongated
      particles. During the evolution toward the final Mg5Si6 particles, the
      compositional change is accompanied by a characteristic structural change. Our
      study explains the nanoscopic reasons that the alloys make excellent automotive
      materials.

PMID- 16627741
TI  - Timing and climatic consequences of the opening of Drake Passage.
AB  - Age estimates for the opening of Drake Passage range from 49 to 17 million years
      ago (Ma), complicating interpretations of the relationship between ocean
      circulation and global cooling. Secular variations of neodymium isotope ratios at
      Agulhas Ridge (Southern Ocean, Atlantic sector) suggest an influx of shallow
      Pacific seawater approximately 41 Ma. The timing of this connection and the
      subsequent deepening of the passage coincide with increased biological
      productivity and abrupt climate reversals. Circulation/productivity linkages are
      proposed as a mechanism for declining atmospheric carbon dioxide. These results
      also indicate that Drake Passage opened before the Tasmanian Gateway, implying
      the late Eocene establishment of a complete circum-Antarctic pathway.

PMID- 16627742
TI  - Asymmetric coevolutionary networks facilitate biodiversity maintenance.
AB  - The mutualistic interactions between plants and their pollinators or seed
      dispersers have played a major role in the maintenance of Earth's biodiversity.
      To investigate how coevolutionary interactions are shaped within species-rich
      communities, we characterized the architecture of an array of quantitative,
      mutualistic networks spanning a broad geographic range. These coevolutionary
      networks are highly asymmetric, so that if a plant species depends strongly on an
      animal species, the animal depends weakly on the plant. By using a simple
      dynamical model, we showed that asymmetries inherent in coevolutionary networks
      may enhance long-term coexistence and facilitate biodiversity maintenance.

PMID- 16627743
TI  - Stability via asynchrony in Drosophila metapopulations with low migration rates.
AB  - Very few experimental studies have examined how migration rate affects
      metapopulation dynamics and stability. We studied the dynamics of replicate
      laboratory metapopulations of Drosophila under different migration rates. Low
      migration stabilized metapopulation dynamics, while promoting unstable
      subpopulation dynamics, by inducing asynchrony among neighboring subpopulations.
      High migration synchronized subpopulation dynamics, thereby destabilizing the
      metapopulations. Contrary to some theoretical predictions, increased migration
      did not affect average population size. Simulations based on a simple non-species
      specific population growth model captured most features of the data, which
      suggests that our results are generalizable.

PMID- 16627744
TI  - A plant miRNA contributes to antibacterial resistance by repressing auxin
      signaling.
AB  - Plants and animals activate defenses after perceiving pathogen-associated
      molecular patterns (PAMPs) such as bacterial flagellin. In Arabidopsis,
      perception of flagellin increases resistance to the bacterium Pseudomonas
      syringae, although the molecular mechanisms involved remain elusive. Here, we
      show that a flagellin-derived peptide induces a plant microRNA (miRNA) that
      negatively regulates messenger RNAs for the F-box auxin receptors TIR1, AFB2, and
      AFB3. Repression of auxin signaling restricts P. syringae growth, implicating
      auxin in disease susceptibility and miRNA-mediated suppression of auxin signaling
      in resistance.

PMID- 16627745
TI  - Nuclear pores form de novo from both sides of the nuclear envelope.
AB  - Nuclear pore complexes are multiprotein channels that span the double lipid
      bilayer of the nuclear envelope. How new pores are inserted into the intact
      nuclear envelope of proliferating and differentiating eukaryotic cells is
      unknown. We found that the Nup107-160 complex was incorporated into assembly
      sites in the nuclear envelope from both the nucleoplasmic and the cytoplasmic
      sides. Nuclear pore insertion required the generation of Ran guanosine
      triphosphate in the nuclear and cytoplasmic compartments. Newly formed nuclear
      pore complexes did not contain structural components of preexisting pores,
      suggesting that they can form de novo.

PMID- 16627746
TI  - Differential targeting of Gbetagamma-subunit signaling with small molecules.
AB  - G protein betagamma subunits have potential as a target for therapeutic treatment
      of a number of diseases. We performed virtual docking of a small-molecule library
      to a site on Gbetagamma subunits that mediates protein interactions. We
      hypothesized that differential targeting of this surface could allow for
      selective modulation of Gbetagamma subunit functions. Several compounds bound to
      Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated
      functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide
      signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia
      in vivo. These data demonstrate an approach for modulation of G protein-coupled
      receptor signaling that may represent an important therapeutic strategy.

PMID- 16627747
TI  - EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and
      potential anti-inflammatory drug for treating cystic fibrosis.
AB  - EPI-hNE4 (depelstat) is a potent inhibitor of human neutrophil elastase derived
      from human inter-alpha-trypsin inhibitor and designed to control the excess
      proteolytic activity in the sputum of cystic fibrosis patients. We analyzed its
      resistance to the proteolysis it is likely to encounter at inflammatory sites in
      vivo. EPI-hNE4 resisted hydrolysis by neutrophil matrix metalloproteases (MMPs)
      and serine proteases that are released from activated neutrophils in inflammatory
      lung secretions, including MMP-8 and MMP-9, and the elastase-related protease 3
      and cathepsin G. It also resisted degradation by epithelial lung cell MMP-7 but
      was broken down by the Pseudomonas aeruginosa metalloelastase pseudolysin, when
      used in a purified system, but not when this protease competed with equimolar
      amounts of neutrophil elastase. We also investigated the inhibitory properties of
      EPI-hNE4 at the surface of purified blood neutrophils and in the sputum of cystic
      fibrosis patients where neutrophil elastase is in both a soluble and a gel phase.
      The elastase at the neutrophil surface was fully inhibited by EPI-hNE4 and formed
      soluble complexes. The elastase in cystic fibrosis sputum supernatants was
      inhibited by stoichiometric amounts of EPI-hNE4, allowing titration of the
      protease. But the percentage of inhibition in whole sputum homogenates varied
      from 50 to 100%, depending on the sample tested. EPI-hNE4 was rapidly cleaved by
      the digestive protease pepsin in vitro. Therefore, EPI-hNE4 seems to be an
      elastase inhibitor suitable for use in aerosols to treat patients with cystic
      fibrosis.

PMID- 16627748
TI  - Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in
      rat and human livers.
AB  - Although Oatp1a1 (rat organic anion-transporting polypeptide 1a1) was the
      transporter found responsible for the hepatocellular entry of enalapril (EN) into
      the rat liver, the canalicular transporter involved for excretion of EN and the
      metabolite, enalaprilat (ENA), was unknown. The Eisai hyperbilirubinemic rat
      (EHBR) that lacks Mrp2 (multidrug resistance-associated protein 2) was used to
      appraise the role of Mrp2 in the excretion of [3H]EN and its metabolite [3H]ENA
      in single-pass rat liver preparations. Although the total and metabolic
      clearances and hepatic extraction ratios at steady-state were virtually unaltered
      for EN in EHBR compared with published values of Sprague-Dawley rats, the biliary
      clearances of EN and ENA were significantly reduced almost to zero (P<0.05).
      Involvement of human OATP1B1, OATP1B3, and MRP2 in EN transport was further
      assessed in single- or double-transfected mammalian cells. Human embryonic kidney
      293 cells that expressed OATP1B1 or OATP1B3 showed that OATP1B3 transport of EN
      (20-500 microM) was of low affinity, whereas transport of EN by OATP1B1 was
      associated with the Km of 262+/-35 microM, a value similar to that for Oatp1a1
      (214 microM). The transcellular transport of EN via human OATP1B1 and MRP2,
      investigated with the double-transfected Madin-Darby canine kidney (MDCK) II
      cells in the Transwell system, showed that the sinusoidal to canalicular flux of
      EN in the OATP1B1/MRP2/MDCK cells was significantly higher (P<0.05) than that of
      mock/MDCK and OATP1B1/MDCK cells. EN was transported by Oatp1a1 and Mrp2 in rats
      and OATP1B1/OATP1B3 and MRP2 in humans.

PMID- 16627749
TI  - Alcohol use, vascular disease, and lipid-lowering drugs.
AB  - Many epidemiological and clinical studies have shown that light-to-moderate
      alcohol (Alc) consumption is associated with reduced risk of coronary heart
      disease (CHD) and total mortality in middle-aged and elderly men and women. The
      plausible mechanisms for the putative cardioprotective effects include increased
      levels of high-density lipoprotein cholesterol, prevention of clot formation,
      reduced platelet aggregation, promotion of blood clot dissolution, and lowering
      of plasma lipoprotein (a) concentration. Individuals who need to be treated with
      lipid-lowering drugs, such as dyslipidemic or CHD patients, may benefit from
      these effects of Alc. Because hypolipidemic treatment is usually continued for
      life, an important issue is the suitability of Alc consumption in these patients.
      In the present review, the beneficial effects of Alc consumption on CHD risk, its
      side effects, and its safety and suitability when coadministered with
      hypolipidemic drugs are discussed.

PMID- 16627750
TI  - Inhibition of protein kinase c-Src reduces the incidence of breast cancer
      metastases and increases survival in mice: implications for therapy.
AB  - c-Src is a proto-oncogene, belonging to the nonreceptor protein kinases family,
      which plays a prominent role in carcinogenesis. In this study, we tested the
      hypothesis that c-Src could promote breast cancer metastasis acting on several
      cell types and that pharmacological disruption of its kinase activity could be
      beneficial for the treatment of metastases. Female BALB/c-nu/nu mice were
      subjected to intracardiac injection of the human breast cancer cells MDA-MB-231
      (MDA-231), which induced prominent bone and visceral metastases. These were
      pharmacologically reduced by treatment with the c-Src inhibitor [7-{4-[2-(2
      methoxy-ethylamino-ethoxy]-phenyl}-5-(3-methoxy-phenyl)-7H-pyrrolo[2,3
      d]pyrimidin-4-ylamine] CGP76030 (100 mg/kg/day p.o.), resulting in decreased
      morbidity and lethality. Metastases were more severe in mice injected with MDA
      231 cells stably transfected with wild-type c-Src (MDA-231-SrcWT), whereas
      transfection in injected cells of a c-Src kinase-dead dominant-negative construct
      (MDA-231-SrcDN) resulted in reduced morbidity, lethality, and incidence of
      metastases similar to the mice treated with the inhibitor. An analogous
      beneficial effect of c-Src inhibition was observed in subcutaneous and
      intratibial implanted tumors. In vitro, c-Src suppression reduced MDA-231 cell
      aggressiveness. It also impaired osteoclast bone resorption both directly and by
      reducing expression by osteoblasts of the osteoclastogenic cytokines interleukin
      1beta and interleukin-6, whereas parathyroid hormone-related peptide was not
      implicated. c-Src was also modestly but consistently involved in the enhancement
      of endothelial cell proliferation in vitro and angiogenesis in vivo. In
      conclusion, we propose that c-Src disruption affects the metastatic process and
      thus is a therapeutic target for the treatment of breast cancer.

PMID- 16627751
TI  - Experimental and modeling studies of desensitization of P2X3 receptors.
AB  - The function of ATP-activated P2X3 receptors involved in pain sensation is
      modulated by desensitization, a phenomenon poorly understood. The present study
      used patch-clamp recording from cultured rat or mouse sensory neurons and kinetic
      modeling to clarify the properties of P2X3 receptor desensitization. Two types of
      desensitization were observed, a fast process (t1/2 = 50 ms; 10 microM ATP)
      following the inward current evoked by micromolar agonist concentrations, and a
      slow process (t1/2 = 35 s; 10 nM ATP) that inhibited receptors without activating
      them. We termed the latter high-affinity desensitization (HAD). Recovery from
      fast desensitization or HAD was slow and agonist-dependent. When comparing
      several agonists, there was analogous ranking order for agonist potency, rate of
      desensitization and HAD effectiveness, with 2-methylthioadenosine triphosphate
      the strongest and beta,gamma-methylene-ATP the weakest. HAD was less developed
      with recombinant (ATP IC50 = 390 nM) than native P2X3 receptors (IC50 = 2.3 nM).
      HAD could also be induced by nanomolar ATP when receptors seemed to be
      nondesensitized, indicating that resting receptors could express high-affinity
      binding sites. Desensitization properties were well accounted for by a cyclic
      model in which receptors could be desensitized from either open or closed states.
      Recovery was assumed to be a multistate process with distinct kinetics dependent
      on the agonist-dependent dissociation rate from desensitized receptors. Thus, the
      combination of agonist-specific mechanisms such as desensitization onset, HAD,
      and resensitization could shape responsiveness of sensory neurons to P2X3
      receptor agonists. By using subthreshold concentrations of an HAD-potent agonist,
      it might be possible to generate sustained inhibition of P2X3 receptors for
      controlling chronic pain.

PMID- 16627752
TI  - A homozygous Fas ligand gene mutation in a patient causes a new type of
      autoimmune lymphoproliferative syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by
      lymphoproliferation and autoimmune clinical manifestations and is generally
      caused by defective Fas-mediated apoptosis. This report describes the first
      homozygous FASL gene mutation in a woman with clinical and immunologic features
      of ALPS. T-cell blasts from the patient did not induce FasL-mediated apoptosis on
      Fas-transfected murine L1210 or on Jurkat cells, and activation-induced cell
      death was impaired. Furthermore, Fas-dependent cytotoxicity was drastically
      reduced in COS cells transfected with the mutant FasL. In addition, FasL
      expression on T-cell blasts from the patient was similar to that observed in a
      healthy control, despite its bearing the high-producer genotype -844C/C in the
      FASL promoter. Sequencing of the patient's FASL gene revealed a new mutation in
      exon 4 (A247E). The location of A247E in the FasL extracellular domain and the
      conservation of the protein sequence of that region recorded in 8 species
      different from humans support the essential role of FasL COOH terminal domain in
      Fas/FasL binding. These findings provide evidence that inherited nonlethal FASL
      abnormalities cause an uncommon apoptosis defect producing lymphoproliferative
      disease, and they highlight the need for a review of the current ALPS
      classification to include a new ALPS type Ic subgroup.

PMID- 16627753
TI  - Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and
      terminal maturation and is thereby an important enhancer of definitive
      erythropoiesis during mouse development.
AB  - Erythropoiesis, the essential process of hematopoietic stem cell development into
      erythrocytes, is controlled by lineage-specific transcription factors that
      determine cell fate and differentiation and by the hormone erythropoietin that
      stimulates cell survival and proliferation. Here we identify the Sry-related high
      mobility-group (HMG) box transcription factor Sox6 as an important enhancer of
      definitive erythropoiesis. Sox6 is highly expressed in proerythroblasts and
      erythroblasts in the fetal liver, neonatal spleen, and bone marrow. Mouse fetuses
      and pups lacking Sox6 develop erythroid cells slowly and feature misshapen, short
      lived erythrocytes. They compensate for anemia by elevating the serum level of
      erythropoietin and progressively enlarging their erythropoietic tissues.
      Erythroid-specific inactivation of Sox6 causes the same phenotype, demonstrating
      cell-autonomous roles for Sox6 in erythroid cells. Sox6 potentiates the ability
      of erythropoietin signaling to promote proerythroblast survival and has an effect
      additive to that of erythropoietin in stimulating proerythroblast and
      erythroblast proliferation. Sox6 also critically facilitates erythroblast and
      reticulocyte maturation, including hemoglobinization, cell condensation, and
      enucleation, and ensures erythrocyte cytoskeleton long-term stability. It does
      not control adult globin and erythrocyte cytoskeleton genes but acts by
      stabilizing filamentous actin (F-actin) levels. Sox6 thus enhances erythroid cell
      development at multiple levels and thereby ensures adequate production and
      quality of red blood cells.

PMID- 16627754
TI  - High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a
      low risk of GVHD following HLA-matched allogeneic SCT.
AB  - Regulatory T cells (T(reg)s) that constitutively express FOXP3 are instrumental
      to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD)
      in humans. To determine whether regulatory T cells in allogeneic stem cell
      transplants (SCTs) ameliorate GVHD after transplantation, we quantitated the
      coexpression of FOXP3 on CD4(+) T cells in 32 donor SCTs infused into HLA-matched
      siblings and examined GVHD incidence in respective recipients. High
      CD4(+)FOXP3(+) T-cell count in the donor was associated with a reduced risk of
      GVHD. We monitored T(reg)s during immune reconstitution in 21 patients with
      leukemia undergoing a T-cell-depleted allogeneic SCT. Early after SCT, there was
      a significant expansion in the CD4(+)FOXP3(+) T-cell compartment. A low
      CD4(+)FOXP3(+) T-cell count early after SCT (day 30) was associated with an
      increased risk of GVHD, and the ratio of CD4(+)FOXP3(+) T cells to
      CD4(+)CD25(+)FOXP3(-) T cells was significantly reduced in patients with GVHD,
      suggesting diminished control of effector T cells. Our findings suggest that
      graft T(reg) content may predict for risk of GVHD after SCT. Determining the
      T(reg) levels in the donor and manipulating T(reg)s early after transplantation
      may provide a new approach to controlling GVHD.

PMID- 16627755
TI  - Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by
      imatinib mesylate.
AB  - Imatinib mesylate (IM) therapy for chronic myeloid leukemia (CML) has transformed
      the treatment of this disease. However, the vast majority of patients, despite
      major responses, still harbor Philadelphia chromosome-positive (Ph(+)) cells. We
      have described a population of primitive Ph(+) cells that are insensitive to IM
      and may be a source of IM resistance. Cell line studies have suggested that the
      drug transporter ABCG2 may be a mediator of IM resistance, however there is
      considerable debate about whether IM is an ABCG2 substrate or inhibitor. We
      demonstrate here that primitive CML CD34(+) cells aberrantly overexpress
      functional ABCG2 but that cotreatment with IM and an ABCG2 inhibitor does not
      potentiate the effect of IM. We definitively show that IM is an inhibitor of, but
      not a substrate for, ABCG2 and that, therefore, ABCG2 does not modulate
      intracellular concentrations of IM in this clinically relevant cell population.

PMID- 16627756
TI  - Survival advantage from imatinib compared with the combination interferon-alpha
      plus cytarabine in chronic-phase chronic myelogenous leukemia: historical
      comparison between two phase 3 trials.
AB  - In the multinational IRIS study comparing imatinib with interferon plus
      cytarabine (IFN/Ara-C) in patients with newly diagnosed chronic-phase chronic
      myelogenous leukemia (CP CML), imatinib demonstrated significantly higher rates
      of complete cytogenetic responses (CCyRs) and improved progression-free survival
      (PFS). However, because of a high early crossover rate to imatinib, survival
      benefit was not assessable. Here, we report the result of a study comparing long
      term outcome of patients included in 2 prospective randomized trials: 551
      patients assigned to imatinib in the IRIS trial from 2000 to 2001 and 325
      patients who received the combination IFN/Ara-C in the CML91 trial between 1991
      and 1996 before imatinib was available. With a follow-up of 42 months for both
      groups of patients, estimated CCyR, survival free of transformation, and overall
      survival were significantly higher with imatinib compared with IFN/Ara-C (P <
      .001, P = .004, and P < .001, respectively). Improved overall survival was also
      confirmed within different Sokal prognostic risk groups. Of interest, among all
      patients who achieved major cytogenetic response or CCyR at 12 months, the
      survival rate was similar irrespective of their treatment. In conclusion, within
      the limitation of this historical comparison, there is a survival advantage from
      first-line therapy with imatinib over IFN/Ara-C.

PMID- 16627757
TI  - Role of a 5'-enhancer in the transcriptional regulation of the human endothelial
      cell protein C receptor gene.
AB  - The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells
      of large blood vessels and by hematopoietic stem cells. DNaseI hypersensitive
      (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3
      potential regulatory elements. By itself, the DH region spanning the proximal
      promoter (PP) was unable to direct cell-specific transcription in transgenic
      mice. A second DH element, located upstream of PP and termed -5.5HS was
      hypersensitive only in endothelial cells (ECs) and immature hematopoietic cell
      lines. Transgenes expressing LacZ under the control of -5.5HS coupled to either
      PP or the SV40 promoter were able to direct beta-galactosidase activity to the
      endothelium of large vessels during embryogenesis and adulthood. The -5.5HS
      exhibited enhancer activity that was conferred by the interplay of transcription
      factors interacting with conserved Ets and composite GATA/Tal1 motifs. The third
      DH element, located in intron 2, was primarily hypersensitive in EPCR-negative
      cells, and capable of initiating antisense transcription, suggesting a role in
      hEPCR silencing. This study identifies critical elements required for the tissue
      specificity of hEPCR and suggests a mechanism for endothelial and hematopoietic
      stem cell-specific transcriptional regulation that reflects the common origin of
      these cell types.

PMID- 16627758
TI  - Endothelial stroma programs hematopoietic stem cells to differentiate into
      regulatory dendritic cells through IL-10.
AB  - Regulatory dendritic cells (DCs) have been reported recently, but their origin is
      poorly understood. Our previous study demonstrated that splenic stroma can drive
      mature DCs to proliferate and differentiate into regulatory DCs, and their
      natural counterpart with similar regulatory function in normal spleens has been
      identified. Considering that the spleen microenvironment supports hematopoiesis
      and that hematopoietic stem cells (HSCs) are found in spleens of adult mice, we
      wondered whether splenic microenvironment could differentiate HSCs into
      regulatory DCs. In this report, we demonstrate that endothelial splenic stroma
      induce HSCs to differentiate into a distinct regulatory DC subset with high
      expression of CD11b but low expression of Ia. CD11b(hi)Ia(lo) DCs secreting high
      levels of TGF-beta, IL-10, and NO can suppress T-cell proliferation both in vitro
      and in vivo. Furthermore, CD11b(hi)Ia(lo) DCs have the ability to potently
      suppress allo-DTH in vivo, indicating their preventive or therapeutic
      perspectives for some immunologic disorders. The inhibitory function of
      CD11b(hi)Ia(lo) DCs is mediated through NO but not through induction of
      regulatory T (Treg) cells or T-cell anergy. IL-10, which is secreted by
      endothelial splenic stroma, plays a critical role in the differentiation of the
      regulatory CD11b(hi)Ia(lo) DCs from HSCs. These results suggest that splenic
      microenvironment may physiologically induce regulatory DC differentiation in
      situ.

PMID- 16627759
TI  - Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by
      FLT3-ITD.
AB  - Acquired mutations in the FLT3 receptor tyrosine kinase are common in acute
      myeloid leukemia and result in constitutive activation. The most frequent
      mechanism of activation is disruption of the juxtamembrane autoregulatory domain
      by internal tandem duplications (ITDs). FLT3-ITDs confer factor-independent
      growth to hematopoietic cells and induce a myeloproliferative syndrome in murine
      bone marrow transplant models. We and others have observed that FLT3-ITD
      activates STAT5 and its downstream effectors, whereas ligand-stimulated wild-type
      FLT3 (FLT3WT) does not. In vitro mapping of tyrosine phosphorylation sites in
      FLT3-ITD identified 2 candidate STAT5 docking sites within the juxtamembrane
      domain that are disrupted by the ITD. Tyrosine to phenylalanine substitution of
      residues 589 and 591 in the context of the FLT3-ITD did not affect tyrosine
      kinase activity, but abrogated STAT5 activation. Furthermore, FLT3-ITD-Y589/591F
      was incapable of inducing a myeloproliferative phenotype when transduced into
      primary murine bone marrow cells, whereas FLT3-ITD induced myeloproliferative
      disease with a median latency of 50 days. Thus, the conformational change in the
      FLT3 juxtamembrane domain induced by the ITD activates the kinase through
      dysregulation of autoinhibition and results in qualitative differences in signal
      transduction through STAT5 that are essential for the transforming potential of
      FLT3-ITD in vivo.

PMID- 16627760
TI  - Genes contributing to minimal residual disease in childhood acute lymphoblastic
      leukemia: prognostic significance of CASP8AP2.
AB  - In childhood acute lymphoblastic leukemia (ALL), early response to treatment is a
      powerful prognostic indicator. To identify genes associated with this response,
      we analyzed gene expression of diagnostic lymphoblasts from 189 children with ALL
      and compared the findings with minimal residual disease (MRD) levels on days 19
      and 46 of remission induction treatment. After excluding genes associated with
      genetic subgroups, we identified 17 genes that were significantly associated with
      MRD. The caspase 8-associated protein 2 (CASP8AP2) gene was studied further
      because of its reported role in apoptosis and glucocorticoid signaling. In a
      separate cohort of 99 patients not included in the comparison of gene expression
      profiles and MRD, low levels of CASP8AP2 expression predicted a lower event-free
      survival (P = .02) and a higher rate of leukemia relapse (P = .01) and were an
      independent predictor of outcome. High levels of CASP8AP2 expression were
      associated with a greater propensity of leukemic lymphoblasts to undergo
      apoptosis. We conclude that measurement of CASP8AP2 expression at diagnosis
      offers a means to identify patients whose leukemic cells are highly susceptible
      to chemotherapy. Therefore, this gene is a strong candidate for inclusion in gene
      expression arrays specifically designed for leukemia diagnosis.

PMID- 16627761
TI  - Proprotein convertase furin is preferentially expressed in T helper 1 cells and
      regulates interferon gamma.
AB  - Interleukin 12 (IL-12) is a major inducer of interferon gamma (IFN-gamma) and the
      principal mediator of T helper 1 (Th1) differentiation. To identify IL-12
      regulated genes, which might contribute to Th1 differentiation and IFNG
      regulation, we employed microarray analysis. Surprisingly, a ubiquitously
      expressed proprotein convertase (PC), furin, was one of the most consistently IL
      12-induced genes in T cells, and among PCs was the only one regulated by this
      cytokine. Furin was preferentially expressed in differentiated Th1 cells in a
      Stat4-dependent manner. Expression of furin enhanced IFN-gamma secretion, whereas
      inhibition of furin interfered with IFN-gamma production. Thus, we conclude that
      IL-12 induction of furin might represent a new aspect of IFN-gamma regulation and
      control of Th1 differentiation.

PMID- 16627763
TI  - Oral chelators deferasirox and deferiprone for transfusional iron overload in
      thalassemia major: new data, new questions.
AB  - For nearly 30 years, patients with transfusional iron overload have depended on
      nightly deferoxamine infusions for iron chelation. Despite dramatic gains in life
      expectancy in the deferoxamine era for patients with transfusion-dependent
      anemias, the leading cause of death for young adults with thalassemia major and
      related disorders has been cardiac disease from myocardial iron deposition.
      Strategies to reduce cardiac disease by improving chelation regimens have been of
      the highest priority. These strategies have included development of novel oral
      iron chelators to improve compliance, improved assessment of cardiac iron status,
      and careful epidemiologic assessment of European outcomes with deferiprone, an
      oral alternative chelator available for about a decade. Each of these strategies
      is now bearing fruit. The novel oral chelator deferasirox was recently approved
      by the Food and Drug Administration (FDA); a randomized clinical trial
      demonstrates that deferasirox at 20 to 30 mg/kg/d can maintain or improve hepatic
      iron in thalassemia as well as deferoxamine. A randomized trial based on cardiac
      T2* magnetic resonance imaging (MRI) suggests that deferiprone can unload
      myocardial iron faster than deferoxamine. Retrospective epidemiologic data
      suggest dramatic reductions in cardiac events and mortality in Italian subjects
      exposed to deferiprone compared with deferoxamine. These developments herald a
      new era for iron chelation, but many unanswered questions remain.

PMID- 16627764
TI  - Recipient gammadelta T cells in graft-versus-host disease.

PMID- 16627765
TI  - Assessing the risk of inhibitor formation with different factor VIII products.

PMID- 16627766
TI  - A novel deletion causing alpha thalassemia clarifies the importance of the major
      human alpha globin regulatory element.

PMID- 16627767
TI  - Still's concept of connective tissue: lost in "translation"?

PMID- 16627768
TI  - Credit where credit's due: forebears of the Osteopathic Research Center.

PMID- 16627769
TI  - Whole person medicine: a definition articulated osteopathically.

PMID- 16627770
TI  - Continuity of thought and tradition in the discipline supported by ongoing AOA
      efforts.

PMID- 16627772
TI  - Women's reproductive health and neonatal care.

PMID- 16627773
TI  - Risk factors for postpartum depression: a retrospective investigation at 4-weeks
      postnatal and a review of the literature.
AB  - OBJECTIVE: To describe possible correlations between incidence of postpartum
      depression and the following patient characteristics: age, breastfeeding status,
      tobacco use, marital status, history of depression, and method of delivery. STUDY
      DESIGN: Data gathered at routine 4-week postnatal visits were obtained from the
      patient records of 209 women who gave birth between June 1, 2001, and June 1,
      2003, at three university medical clinics in Tulsa, Okla. Inclusion criteria
      required that the records of potential study subjects contain data on the
      characteristics noted as well as patient-completed Edinburgh Postnatal Depression
      Scale forms. RESULTS: Formula feeding in place of breastfeeding, a history of
      depression, and cigarette smoking were all significant risk factors for an
      Edinburgh Postnatal Depression Scale score of 13 or higher, indicating probable
      postpartum depression. CONCLUSION: The authors' findings corroborate the results
      of previous investigators. To facilitate prophylactic patient education and
      intervention strategies, a larger study is recommended to determine risk factors
      for postpartum depression.

PMID- 16627774
TI  - Postpartum outcomes in supine delivery by physicians vs nonsupine delivery by
      midwives.
AB  - CONTEXT: Clinically preferred maternal position during childbirth has varied
      between supine and nonsupine over time and from patient to patient. Preferred
      maternal birthing position is coming under increasing scrutiny. OBJECTIVE: To
      compare postpartum maternal and infant outcomes resulting from supine and
      nonsupine positions maintained during the second stage of labor. DESIGN AND
      METHODS: Nonrandomized clinical trial comparing low-risk women (N=198) in two
      separate obstetrics practices. In one practice, parturients (n=100) used only the
      supine position as their birthing position. In the other practice, parturients
      (n=98) used any or all of three nonsupine positions (sitting, squatting, or
      kneeling/hands-and-knees). Data collection took place immediately after birth by
      provider survey and included: Apgar scores, demographics, estimated blood loss,
      neonatal weight, perineal integrity, position during second-stage labor and
      birth, and vulvar edema. RESULTS: Infants born to mothers in nonsupine positions
      were delivered with significantly less tearing of the perineum (P<.001) and less
      vulvar edema (P<.001). Although the length of second-stage labor was shorter
      among the women who were nonsupine, this result lacked statistical significance.
      There did not appear to be increased risk to the infant from the mother's
      nonsupine posture. CONCLUSION: Nonsupine positions during labor and delivery were
      found to have clinical advantages without risk to mother or infant. Enhanced
      maternal outcomes included improved perineal integrity, less vulvar edema, and
      less blood loss.

PMID- 16627775
TI  - Breastfeeding, the immune response, and long-term health.
AB  - Breastfeeding provides unsurpassed natural nutrition to the newborn and infant.
      Human breast milk also contains numerous protective factors against infectious
      disease and may influence immune system development, as noted in previous studies
      of infant response to vaccination and thymus gland development. If immune system
      development is significantly improved with the introduction of components of
      breast milk, then prematurely discontinued breastfeeding may facilitate
      pathogenesis of many chronic diseases later in life (eg, autoimmune disorders).
      The authors summarize the reported effects of breastfeeding on the development of
      the suckling infant's immune system and discuss possible consequences to
      immunologic health when breastfeeding is discontinued prematurely.

PMID- 16627776
TI  - Medical and legal issues related to brachial plexus injuries in neonates.
AB  - Injuries to the brachial plexus in neonates present a malpractice dilemma not
      only for physicians who provide obstetric care, but also for those who administer
      immediate postnatal treatment for newborns who have these injuries and comorbid
      medical conditions. Although trauma remains the probable etiology for many
      brachial plexus injuries, other, nontraumatic etiologies need to be considered.
      The authors review current medical and legal principles related to brachial
      plexus injuries-principles that are of concern to all practitioners who provide
      obstetric and newborn care. They also make a number of recommendations for
      practitioners to reduce the risk of malpractice lawsuits related to these
      injuries. Among these recommendations are increasing one's awareness of
      nontraumatic origins; making sure that appropriate testing (eg, electromyography)
      is performed for infants whose conditions fail to improve within several months
      after birth; and taking a proactive role in discussing brachial plexus injuries
      with patients' families.

PMID- 16627778
TI  - Let the beauty of the marketplace benefit healthcare.

PMID- 16627780
TI  - Residents' wisdom regarding narcotics.

PMID- 16627781
TI  - Calling all osteopathic physicians in New England!

PMID- 16627782
TI  - Follow precautions when prescribing opioids.

PMID- 16627783
TI  - Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling.
AB  - Intima-media thickening (IMT) in response to hemodynamic stress is a
      physiological process that requires coordinated signaling among endothelial,
      inflammatory, and vascular smooth muscle cells (VSMC). Axl, a receptor tyrosine
      kinase, whose ligand is Gas6, is highly induced in VSMC after carotid injury.
      Because Axl regulates cell migration, phagocytosis and apoptosis, we hypothesized
      that Axl would play a role in IMT. Vascular remodeling in mice deficient in Axl
      (Axl(-/-)) and wild-type littermates (Axl(+/+)) was induced by ligation of the
      left carotid artery (LCA) branches maintaining flow via the left occipital
      artery. Both genotypes had similar baseline hemodynamic parameters and carotid
      artery structure. Partial ligation altered blood flow equally in both genotypes:
      increased by 60% in the right carotid artery (RCA) and decreased by 80% in the
      LCA. There were no significant differences in RCA remodeling between genotypes.
      However, in the LCA Axl(-/-) developed significantly smaller intima+media
      compared with Axl(+/+) (31+/-4 versus 42+/-6x10(-6) microm3, respectively).
      Quantitative immunohistochemistry of Axl(-/-) LCA showed increased apoptosis
      compared with Axl(+/+) (5-fold). As expected, p-Akt was decreased in Axl(-/-),
      whereas there was no difference in Gas6 expression. Cell composition also changed
      significantly, with increases in CD45+ cells and decreases in VSMC, macrophages,
      and neutrophils in Axl(-/-) compared with Axl(+/+). These data demonstrate an
      important role for Axl in flow-dependent remodeling by regulating vascular
      apoptosis and vascular inflammation.

PMID- 16627784
TI  - Insulin-like growth factor-1 and PTEN deletion enhance cardiac L-type Ca2+
      currents via increased PI3Kalpha/PKB signaling.
AB  - Ca2+ influx through the L-type Ca2+ channel (I(Ca,L)) is a key determinant of
      cardiac contractility and is modulated by multiple signaling pathways. Because
      the regulation of I(Ca,L) by phosphoinositide-3-kinases (PI3Ks) and
      phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in
      the regulation of myocardial growth and contractility, I(Ca,L) was recorded in
      myocytes isolated from mice overexpressing a dominant-negative p110alpha mutant
      (DN-p110alpha) in the heart, lacking the PI3Kgamma gene (PI3Kgamma(-/-)) or with
      muscle-specific ablation of PTEN (PTEN(-/-)). Combinations of these genetically
      altered mice were also examined. Although there were no differences in the
      expression level of CaV1.2 proteins, basal I(Ca,L) densities were larger (P<0.01)
      in PTEN(-/-) myocytes compared with littermate controls, PI3Kgamma(-/-), or DN
      p110alpha myocytes and showed negative shifts in voltage dependence of current
      activation. The I(Ca,L) differences seen in PTEN(-/-) mice were eliminated by
      pharmacological inhibition of either PI3Ks or protein kinase B (PKB) as well as
      in PTEN(-/-)/DN-p110alpha double mutant mice but not in PTEN(-/-)/PI3Kgamma(-/-)
      mice. On the other hand, application of insulin-like growth factor-1 (IGF-1), an
      activator of PKB, increased I(Ca,L) in control and PI3Kgamma(-/-), while having
      no effects on I(Ca,L) in DN-p110alpha or PTEN(-/-) mice. The I(Ca,L) increases
      induced by IGF-1 were abolished by PKB inhibition. Our results demonstrate that
      IGF-1 treatment or inactivation of PTEN enhances I(Ca,L) via PI3Kalpha-dependent
      increase in PKB activation.

PMID- 16627785
TI  - A calmodulin-binding site on cyclin E mediates Ca2+-sensitive G1/s transitions in
      vascular smooth muscle cells.
AB  - Calcium transients are known to control several transition points in the
      eukaryotic cell cycle. For example, we have previously shown that a coordinate
      elevation in the intracellular free calcium ion concentration is required for G1-
      to S-phase cell cycle progression in vascular smooth muscle cells (VSMC).
      However, the molecular basis for this Ca2+ sensitivity was not known. Using
      buffers with differing [Ca2+], we found that the kinase activity of mouse and
      human cyclin E/CDK2, but not other G1/S-associated cell cycle complexes, was
      responsive to physiological changes in [Ca2+]. We next determined that this Ca2+
      responsive kinase activity was dependent on a direct interaction between
      calmodulin (CaM), one of the major Ca2+-signal transducers of eukaryotic cells,
      and cyclin E. Pharmacological inhibition of CaM abrogated the Ca2+ sensitivity of
      cyclin E/CDK2 and retarded mouse VSMC proliferation by causing G1 arrest. We next
      defined the presence of a highly conserved 22 amino acid N-terminal CaM-binding
      motif in mammalian cyclin E genes (dissociation constant, 1.5+/-0.1 micromol/L)
      and showed its essential role in mediating Ca2+-sensitive kinase activity of
      cyclin E/CDK2. Mutant human cyclin E protein, lacking this CaM-binding motif, was
      incapable of binding CaM or responding to [Ca2+]. Taken together, these findings
      reveal CaM-dependent cyclin E/CDK2 activity as a mediator of the known Ca2+
      sensitivity of the G1/S transition of VSMC.

PMID- 16627786
TI  - Dexamethasone downregulates calcification-inhibitor molecules and accelerates
      osteogenic differentiation of vascular pericytes: implications for vascular
      calcification.
AB  - Vascular calcification is present in many pathological conditions and is
      recognized as a strong predictor of future cardiovascular events. Current
      evidence suggests that it is a regulated process involving inducing and
      inhibitory molecules. Glucocorticoids have great clinical importance as
      antiinflammatory drugs and can act as potent inducers of osteogenic
      differentiation in vitro. The effect of glucocorticoids on vascular cells in vivo
      remains obscure. Pericytes are pluripotent cells that can differentiate into
      osteoblasts, and recent evidence suggests that they could participate in vascular
      calcification. We hypothesized that the synthetic glucocorticoid dexamethasone
      would enhance the rate of pericyte differentiation and mineralization in vitro
      with a concomitant suppression of calcification-inhibitory molecules. Three weeks
      of dexamethasone treatment induced a 2-fold increase in (1) alkaline phosphatase
      activity, (2) calcium deposition, and (3) the number of nodules formed in vitro;
      and a reduction in the expression of matrix Gla protein (MGP), osteopontin (OPN),
      and vascular calcification-associated factor (VCAF) mRNAs. The glucocorticoid
      receptor antagonist Org 34116 abolished dexamethasone-accelerated pericyte
      differentiation, nodule formation, and mineralization. Data obtained using Org
      34116, the transcription inhibitor actinomycin D, and the protein synthesis
      inhibitor cyclohexamide suggest that MGP, OPN, and VCAF mRNA abundance are
      controlled at different and multiple levels by dexamethasone. This is the first
      report showing that dexamethasone enhances the osteogenic differentiation of
      pericytes and downregulates genes associated with inhibition of mineralization.
      Our study highlights the need for further investigation into the long-term
      consequences of prolonged glucocorticoid therapy on vascular calcification.

PMID- 16627787
TI  - Impaired glucose tolerance increases stroke risk in nondiabetic patients with
      transient ischemic attack or minor ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Impaired glucose tolerance, an intermediate metabolic
      state between normal glucose and diabetes characterized by nonfasting glucose
      levels between 7.8 to 11.0 mmol/L, is associated with an increased stroke risk in
      patients with coronary heart disease. Whether impaired glucose tolerance
      increases the risk of stroke in patients with transient ischemic attack (TIA) or
      minor ischemic stroke is unknown. METHODS: In total, 3127 patients with a TIA or
      minor ischemic stroke participated in the Dutch TIA Trial, testing 2 different
      doses of aspirin and atenolol versus placebo. We estimated the risk of stroke and
      the risk of myocardial infarction or cardiac death in relation to baseline
      nonfasting glucose levels (mean 6.0, SD 2.2 mmol/L) with Cox proportional hazards
      regression analysis, adjusted for cardiovascular risk factors. RESULTS: During
      2.6 years follow-up, 272 patients (9%) experienced a stroke and 200 (6%) a
      myocardial infarction or cardiac death. We found a J-shaped relationship between
      baseline nonfasting glucose levels and stroke risk. Stroke risk was nearly
      doubled in patients with impaired glucose tolerance (glucose 7.8 to 11.0 mmol/L)
      compared with those with normal glucose levels (hazard ratio [HR] 1.8, 95% CI,
      1.1 to 3.0) and nearly tripled in diabetic patients (glucose > or =11.1 mmol/L;
      HR 2.8, 95% CI, 1.9 to 4.1). Patients with low glucose levels (<4.6 mmol/L) had a
      50% increased stroke risk (HR 1.5, 95% CI, 1.0 to 2.2) compared with those with
      normal glucose levels. There was no association between glucose levels and risk
      of myocardial infarction or cardiac death. CONCLUSIONS: Impaired glucose
      tolerance is an independent risk factor for future stroke in nondiabetic patients
      with TIA or minor ischemic stroke.

PMID- 16627788
TI  - Potential contribution of NF-kappaB in neuronal cell death in the glutathione
      peroxidase-1 knockout mouse in response to ischemia-reperfusion injury.
AB  - BACKGROUND AND PURPOSE: We have previously identified an increased susceptibility
      of Gpx1(-/-) mice to increased infarct size after middle cerebral artery
      occlusion (MCAO). This study was designed to elucidate the mechanisms involved in
      elevated neuronal cell death arising from an altered endogenous oxidant state.
      METHODS: Gpx1(-/-) mice were exposed to transient MCAO and reperfusion by
      intraluminal suture blockade. Protein expression of the p65 subunit of
      transcription factor nuclear factor-kappaB (NF-kappaB) was examined by
      immunohistochemistry and Western Analysis. NF-kappaB DNA-protein activity was
      assessed by electrophoretic mobility shift assays (EMSA). Wild-type and Gpx1(-/-)
      mice were exposed to MCAO with or without the NF-kappaB inhibitor,
      pyrrolidinedithiocarbamate (PDTC). RESULTS: Upregulation of the p65 subunit of NF
      kappaB and subsequent p65 phosphorylation at serine 536 was detected in the Gpx1(
      /-) brains after stroke. EMSAs revealed that increased ischemia-enhanced DNA
      binding of NF-kappaB was observed in Gpx1(-/-) mice compared with wild-type.
      Supershift assays indicated that the p50 and p65 subunits participated in the
      bound NF-kappaB complex. The NF-kappaB inhibitor PDTC, a potential antioxidant,
      was able to afford partial neuroprotection in the Gpx1(-/-) mice. CONCLUSIONS: NF
      kappaB is upregulated in the Gpx1(-/-) mouse, and this upregulation contributes
      to the increased cell death seen in the Gpx1(-/-) after MCAO. The activation of
      NF-kappaB may increase the expression of downstream target genes that are
      involved in the progression of neural injury after MCAO.

PMID- 16627789
TI  - Rates of delayed rebleeding from intracranial aneurysms are low after surgical
      and endovascular treatment.
AB  - BACKGROUND AND PURPOSE: Although results of the randomized International
      Subarachnoid Aneurysm Trial suggested that coil embolization was superior to
      surgical clipping 1 year after treatment, a paucity of data on long-term outcomes
      has been a major concern. METHODS: In an ambidirectional cohort study, 9
      institutions with expertise in intracranial aneurysm treatment identified all
      ruptured saccular aneurysms treated 1996 to 1998. After an initial medical record
      review, all patients meeting entry criteria were contacted by postal
      questionnaire or telephone. Possible reruptures were adjudicated independently by
      a neurologist, a neurosurgeon, and a neurointerventional radiologist. Rates of
      delayed (>1 year) and early rerupture and retreatment were evaluated using Kaplan
      Meier survival analysis and the log-rank test. RESULTS: A total of 1010 patients
      (711 surgically clipped, 299 treated with coil embolization) were included.
      Patients treated with coil embolization were older, more likely to have smaller
      aneurysms arising from the posterior circulation, and less likely to have middle
      cerebral artery aneurysms. Rerupture of the index aneurysm after 1 year occurred
      in 1 patient treated with coil embolization during 904 person-years of follow-up
      (annual rate 0.11%) and in no patients treated with surgical clipping during 2666
      person-years (P=0.11). Aneurysm retreatment after 1 year was more frequent in
      patients treated with coil embolization (P<0.0001), but major complications were
      rare during retreatment. CONCLUSIONS: Rerupture of aneurysms treated by either
      coil embolization or surgical clipping is rare after the first year. Late
      retreatment is more common after coil embolization than after clipping but
      complication rates are low. Thus, late events are unlikely to overwhelm
      differences between procedures at 1-year follow-up.

PMID- 16627790
TI  - White matter lesions in an unselected cohort of the elderly: molecular pathology
      suggests origin from chronic hypoperfusion injury.
AB  - BACKGROUND AND PURPOSE: "Incidental" MRI white matter (WM) lesions, comprising
      periventricular lesions (PVLs) and deep subcortical lesions (DSCLs), are common
      in the aging brain. Direct evidence of ischemia associated with incidental WM
      lesions (WMLs) has been lacking, and their pathogenesis is unresolved. METHODS: A
      population-based, postmortem cohort (n=456) of donated brains was examined by MRI
      and pathology. In a subsample of the whole cohort, magnetic resonance images were
      used to sample and compare WMLs and nonlesional WM for molecular markers of
      hypoxic injury. RESULTS: PVL severity was associated with loss of ventricular
      ependyma (P=0.004). For DSCLs, there was arteriolar sclerosis compared with
      normal WM (vessel wall thickness and perivascular enlargement; both P<0.001).
      Capillary endothelial activation (ratio of intercellular adhesion molecule to
      basement membrane collagen IV; P<0.001) and microglial activation (CD68
      expression; P=0.002) were elevated in WMLs. Immunoreactivity for hypoxia
      inducible factors (HIFs) HIF1alpha and HIF2alpha was elevated in DSCLs (P=0.003
      and P=0.005). Other hypoxia-regulated proteins were also increased in WMLs:
      matrix metalloproteinase-7 (PVLs P<0.001; DSCLs P=0.009) and the number of
      neuroglobin-positive cells (WMLs P=0.02) reaching statistical significance. The
      severity of congophilic amyloid angiopathy was associated with increased
      HIF1alpha expression in DSCLs (P=0.04). CONCLUSIONS: The data support a hypoxic
      environment within MRI WMLs. Persistent HIF expression may result from failure of
      normal adaptive mechanisms. WM ischemia appears to be a common feature of the
      aging brain.

PMID- 16627791
TI  - The role of antiplatelet therapy in carotid stenting for ischemic stroke
      prevention.
AB  - BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) is a minimally
      invasive revascularization procedure that has become a popular and acceptable
      treatment option in the United States for high surgical risk patients with
      internal carotid artery atherosclerosis. It is effective and has an acceptable
      risk profile, but ischemic complications caused by distal embolization and
      underlying atherothrombosis persist. SUMMARY OF REVIEW: Atherothrombosis is the
      pathological process that is frequently implicated as the underlying cause of
      stroke, transient ischemic attacks, and most other ischemic vascular disease.
      Critical steps in the development of occlusive episodes are the disruption of
      atherosclerotic plaque and subsequent formation of a platelet-rich mural
      thrombus. Vascular injury as a result of CAS or any other percutaneous
      intervention triggers platelet adhesion, activation, and aggregation, resulting
      in the formation of a mural thrombosis. This risk, in addition to the potential
      risk of embolization to distal sites, provides a rationale for early antiplatelet
      therapy with CAS. The risk of late stent (>30 days after stenting) thrombosis in
      some patients, particularly those receiving drug-eluting stents, provides a
      rationale for prolonged antiplatelet prophylaxis as well as for prophylaxis
      against late atherothrombotic events. Because of the systemic and progressive
      nature of atherothrombosis, protection against ischemic vascular events in other
      arterial beds expands the benefits of long-term antiplatelet therapy.
      CONCLUSIONS: As clinical experience with CAS increases, it is likely that it will
      be used more frequently for patients with occlusive carotid disease. In addition,
      adjunct antiplatelet therapy will play a key role in the continued development of
      CAS.

PMID- 16627792
TI  - Recommendations of the National Heart, Lung, and Blood Institute working group on
      cerebrovascular biology and disease.
AB  - The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call
      working group, consisting of experts in stroke and cerebrovascular biology on
      January 28, 2005. The purpose of this working group was to develop a prioritized
      set of recommendations for NHLBI to establish a focused and comprehensive set of
      research activities in cerebrovascular biology and disease. Three thematic areas
      of research emerged: (1) molecular and cellular neurobiology of cerebral blood
      vessels, focusing on genomics and proteomics, neurovascular signaling and
      cerebrovascular embryogenesis, development and plasticity; (2) resource
      development, involving the development of new methodological approaches for
      normal and altered function of the neurovascular unit, collaborative research,
      and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases
      and translational approaches, addressing vascular mechanisms of disease, the role
      of risk factors, importance of biomarkers with the ultimate goal of developing
      new treatments.

PMID- 16627793
TI  - NMDA receptor antibodies predict adverse neurological outcome after cardiac
      surgery in high-risk patients.
AB  - BACKGROUND AND PURPOSE: The goal of this study was to compare the predictive
      ability of S100B, N-methyl-D-aspartate (NMDA) receptor antibodies (NR2Ab) and C
      reactive protein (CRP) for neurological deficits after cardiac surgery with
      cardiopulmonary bypass (CPB). METHODS: We investigated 557 high-risk adult
      patients who underwent coronary artery or valve replacement surgery using CPB as
      a substudy of a prospective, blinded, multicenter clinical trial. Serum
      concentrations of S100B (n=513 patients), NR2Ab (n=398) and CRP (n=510) were
      measured preoperatively, 24 and 48 hours after CPB. Neurological adverse events
      were assessed at baseline and postoperative days 1 and 2; neurocognitive function
      (mini-mental status examination) was assessed at baseline and on postoperative
      days 1, 7 and 28. RESULTS: Fifty-five (9.9%) patients had moderate or severe
      neurological adverse events (confusion/delirium, transient ischemic attack, or
      stroke) within 48 hours of CPB. Women had significantly more neurological
      complications than men (15.5% versus 7.8%; P=0.007). Ninety-six percent (24/25)
      of patients with NR2Ab concentrations > or =2.0 ng/mL preoperatively had
      neurological complications within 48 hours post-CPB, versus only 5.4% (20/373) of
      patients with NR2Ab concentrations <2.0 ng/mL, resulting in a 17.9-fold increase
      (95% CI, 11.6 to 27.6) in postoperative neurological complications for patients
      with high levels of NR2A antibodies. Preoperative serum S100B and CRP did not
      predict neurological complications from CPB. Decreased mini-mental status
      examination scores for orientation, attention and recall were associated with
      neurological adverse events early after CPB. CONCLUSIONS: Preoperative serum
      concentrations of NR2Ab, but not S100B or CRP, are predictive of severe
      neurological adverse events after CPB. Patients with a positive NR2Ab test (> or
      =2.0 ng/mL) preoperatively were nearly 18 times more likely to experience a
      postoperative neurological event than patients with a negative test (<2.0 ng/mL).

PMID- 16627794
TI  - Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial.
AB  - BACKGROUND AND PURPOSE: The relationship between baseline and recurrent vascular
      events may be important in the targeting of secondary prevention strategies. We
      examined the relationship between initial event and various types of further
      vascular outcomes and associated effects of blood pressure (BP)-lowering.
      METHODS: Subsidiary analyses of the Perindopril Protection Against Recurrent
      Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that
      established the benefits of BP-lowering in 6105 patients (mean age 64 years, 30%
      female) with cerebrovascular disease, randomly assigned to either active
      treatment (perindopril for all, plus indapamide in those with neither an
      indication for, nor a contraindication to, a diuretic) or placebo(s). RESULTS:
      Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater
      risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for
      large artery infarction, P<0.0001 for other events). However, 46% to 92% of
      further vascular outcomes were not of the same type. Active treatment produced
      comparable reductions in the risk of vascular outcomes among patients with a
      broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001
      for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for
      coronary events; P homogeneity=0.4). CONCLUSIONS: Patients with previous vascular
      events are at high risk of recurrences of the same event. However, because they
      are also at risk of other vascular outcomes, a broad range of secondary
      prevention strategies is necessary for their treatment. BP-lowering is likely to
      be one of the most effective and generalizable strategies across a variety of
      major vascular events including stroke and myocardial infarction.

PMID- 16627795
TI  - Leukoaraiosis and ischemia: beyond the myth.

PMID- 16627796
TI  - Regular transfusion lowers plasma free hemoglobin in children with sickle-cell
      disease at risk for stroke.
AB  - BACKGROUND AND PURPOSE: Intravascular hemolysis releases large amounts of free
      hemoglobin (PFH) in plasma of sickle-cell disease (SCD) patients. PFH has been
      associated with harmful endothelial actions including scavenging nitric oxide
      (NO). Whether PFH plays a role in stroke in SCD has not been examined. METHODS:
      Serum levels of PFH, lactate dehydrogenase, and total bilirubin were measured in
      stored sera from children at risk for stroke treated in a randomized controlled
      trial of regular red cell transfusion (STOP study). Baseline and post-treatment
      (approximately 1 year of transfusion) were compared to determine whether
      treatment (which reduces stroke risk by 90%) was associated with reduction in
      markers of hemolysis. RESULTS: Baseline serum PFH values did not differ between
      treatment groups. PFH declined with repeated transfusion from 78.7+/-8.2 mg/dL to
      34.4+/-3.4 mg/dL (P<0.001). With only episodic or no transfusion the drop was
      smaller: 80.9+/-7.5 to 62.8+/-5.0 (P=0.019). The decrease was larger in those
      with regular transfusion (56% versus 22%; P<0.001). Reduction of lactate
      dehydrogenase and total bilirubin was observed only in those on regular
      transfusion. CONCLUSIONS: Regular transfusion which lowers stroke risk is
      associated with a significant reduction in PFH. A role for PFH in promoting
      stroke in SCD should be investigated.

PMID- 16627797
TI  - Poststroke rehabilitation: outcomes and reimbursement of inpatient rehabilitation
      facilities and subacute rehabilitation programs.
AB  - BACKGROUND AND PURPOSE: To assess whether poststroke rehabilitation outcomes and
      reimbursement for Medicare beneficiaries differ across inpatient rehabilitation
      facilities (IRFs) and skilled nursing facility (SNF) subacute rehabilitation
      programs. METHODS: Clinical data were linked with Medicare claims for 58,724
      Medicare beneficiaries with a recent stroke who completed treatment in 1996 or
      1997 in IRFs and subacute rehabilitation SNFs that subscribed to the Uniform Data
      System for Medical Rehabilitation. Outcome measures were discharge destination,
      discharge FIM ratings and Medicare Part A reimbursement during the institutional
      stay. RESULTS: IRF patients that were more likely to have a community-based
      discharge, compared with rehabilitation SNF patients, were patients with mild
      motor disabilities and FIM cognitive ratings of 23 or greater (adjusted odds
      ratio [AOR]=2.19; 95% CI: 1.52 to 3.14), patients with moderate motor
      disabilities (AOR=1.98; 95% CI: 1.49 to 2.61), patients with significant motor
      disabilities (AOR=1.26; 95% CI: 1.01 to 1.57) and patients younger than 82 with
      severe motor disabilities (AOR=1.43; 95% CI: 1.25 to 1.64). IRF patients with
      significant and severe motor disabilities achieved greater motor function of 2 or
      more FIM units compared with rehabilitation SNF patients. Medicare Part A
      payments for IRFs were higher than rehabilitation SNF payments across all
      subgroups. CONCLUSIONS: For most patients, poststroke rehabilitation in the more
      costly and intensive IRFs resulted in higher functional outcomes compared with
      care in a SNF-based rehabilitation program. IRF and SNF outcomes were similar for
      patients with minimal motor disabilities and patients with mild motor
      disabilities and significant cognitive disabilities. Cost-effectiveness analyses
      require considering the costs of the full episode of care.

PMID- 16627798
TI  - Microsurgical clipping or endovascular coiling for ruptured cerebral aneurysms.

PMID- 16627799
TI  - Adipocyte differentiation-related protein promotes fatty acid storage in
      cytosolic triglycerides and inhibits secretion of very low-density lipoproteins.
AB  - OBJECTIVE: We investigated the role of adipocyte differentiation-related protein
      (ADRP) in triglyceride turnover and in the secretion of very low-density
      lipoprotein (VLDL) from McA-RH7777 cells and primary rat hepatocytes. METHODS AND
      RESULTS: An increase in the expression of ADRP increased triglyceride
      accumulation in cytosolic lipid droplets and prevented the incorporation of fatty
      acids into secretable triglycerides, thereby reducing the secretion of
      triglycerides as well as of apolipoprotein B-100 (apoB-100) and apoB-48 VLDL. The
      ability of ADRP to block the secretion of apoB-100 VLDL1 decreased with
      increasing quantities of fatty acids in the medium, indicating a saturable
      process and emphasizing the importance of sequestering of fatty acids for the
      effect of ADRP on VLDL secretion. Knockdown (small interfering RNA) of ADRP
      decreased the pool of cytosolic lipid droplets but increased only the secretion
      of apoB-48 VLDL1. Additionally, there was an increased flow of fatty acids into
      beta-oxidation. CONCLUSIONS: ADRP is essential for the accumulation of
      triglycerides in cytosolic lipid droplets. An increase in ADRP prevents the
      formation of VLDL by diverting fatty acids from the VLDL assembly pathway into
      cytosolic triglycerides, whereas a decrease of the protein increases the sorting
      of fatty acids to beta-oxidation and promotes the secretion of apoB-48 VLDL1.

PMID- 16627800
TI  - Estrogen receptor beta protects the murine heart against left ventricular
      hypertrophy.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) displays significant gender-based
      differences. 17beta-estradiol (E2) plays an important role in this process
      because it can attenuate pressure overload hypertrophy via 2 distinct estrogen
      receptors (ERs): ERalpha and ERbeta. However, which ER is critically involved in
      the modulation of LVH is poorly understood. We therefore used ERalpha-deficient
      (ERalpha-/-) and ERbeta-deficient (ERbeta-/-) mice to analyze the respective ER
      mediated effects. METHODS AND RESULTS: Respective ER-deficient female mice were
      ovariectomized and were given E2 or placebo subcutaneously using 60-day release
      pellets. After 2 weeks, they underwent transverse aortic constriction (TAC) or
      sham operation. In ERalpha-/- animals, TAC led to a significant increase in
      ventricular mass compared with sham operation. E2 treatment reduced TAC induced
      cardiac hypertrophy significantly in wild-type (WT) and ERalpha-/- mice but not
      in ERbeta-/- mice. Biochemical analysis showed that E2 blocked the increased
      phosphorylation of p38-mitogen-activated protein kinase observed in TAC-treated
      ERalpha-/- mice. Moreover, E2 led to an increase of ventricular atrial
      natriuretic factor expression in WT and ERalpha-/- mice. CONCLUSIONS: These
      findings demonstrate that E2, through ERbeta-mediated mechanisms, protects the
      murine heart against LVH.

PMID- 16627801
TI  - Local heat shock priming promotes recanalization of thromboembolized
      microvasculature by upregulation of plasminogen activators.
AB  - OBJECTIVE: Thromboembolization and subsequent microvascular perfusion failure is
      implicated in the pathology of a variety of diseases, including transient
      ischemic attack (TIA), stroke, and myocardial infarction, and also for the
      complications after interventional and microsurgical procedures in coronary heart
      disease and peripheral arterial occlusive disease. In vitro heat shock priming
      has been suggested to induce plasminogen activators, which are the major
      upregulators of the fibrinolytic system. Herein, we determined whether local heat
      shock priming endogenously upregulates plasminogen activators also in vivo, and
      whether this promotes recanalization of thromboembolized microvasculature.
      METHODS AND RESULTS: To induce thromboembolization, a suspension of preformed
      microthrombi (maximum diameter: 40 microm) was injected via the femoral artery
      into the left hindlimbs of anesthetized rats. Local heat shock priming (42.5
      degrees C, 30 minutes) was performed 24 hours before embolization and resulted in
      a significant increase of endothelium-derived plasminogen activator expression.
      The study of the microcirculation by intravital microscopy revealed in all
      tissues analyzed (muscle, periosteum, subcutis, and skin) that heat shock priming
      significantly (P<0.05) accelerates recanalization of the thromboembolized
      microvasculature when compared with nonprimed and sham-primed controls.
      Importantly, the addition of plasminogen activator inhibitor-1 to the
      microthrombi suspension completely blunted the heat shock-induced acceleration of
      microvascular recanalization. CONCLUSIONS: Heat shock induces endogenous
      hyperfibrinolysis by upregulation of plasminogen activators that promote
      recanalization of thromboembolized microvasculature.

PMID- 16627802
TI  - Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein e
      knockout mice.
AB  - OBJECTIVE: All 3 isoforms of the nitric oxide synthase (NOS) are expressed in
      atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects
      atherosclerosis, we studied apoE/nNOSalpha double knockout (DKO) and
      apolipoprotein E (apoE) knockout (KO) control mice. METHODS AND RESULTS: Lesion
      area was significantly increased in male DKO (66%) mice after 14 weeks and in
      female DKO animals (31%) after 24 weeks of "western" diet. Moreover, mean
      arterial blood pressure was significantly reduced in female DKO animals.
      Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO
      animals, residual nNOS staining was caused by the presence of nNOS splice
      variants. Whereas nNOSalpha was present in vessels of KO and absent in DKO
      animals, nNOSgamma was expressed in KO and DKO mice. CONCLUSIONS: nNOSalpha
      protects against atherosclerosis as nNOSalpha deletion leads to an increase in
      plaque formation in apoE/nNOSalpha DKO mice. Female DKO mice showed a significant
      reduction in mean arterial blood pressure. Additionally, we found expression of
      nNOS splice variants in vessels of apoE KO mice. Our data highlights nNOSalpha
      overexpression as a potential therapeutic strategy and naturally occurring splice
      variants that lack exon 2 of the nNOS gene as a potential risk factor for
      vascular disease.

PMID- 16627803
TI  - Lipoprotein-associated phospholipase A2 predicts future cardiovascular events in
      patients with coronary heart disease independently of traditional risk factors,
      markers of inflammation, renal function, and hemodynamic stress.
AB  - OBJECTIVE: We sought to evaluate whether lipoprotein-associated phospholipase A2
      (Lp-PLA2), an emerging marker of cardiovascular risk, is associated with
      prognosis in patients with coronary heart disease (CHD). METHODS AND RESULTS:
      Plasma concentrations and activity of Lp-PLA2 were determined in 1051 patients
      aged 30 to 70 years with CHD who were followed for &4 years. A Cox proportional
      hazards model was used to determine the prognostic value of Lp-PLA2 after
      adjustment for various covariates, including markers of inflammation, renal
      function, and hemodynamic stress. In multivariable analyses, Lp-PLA2 mass and
      activity were strongly associated with cardiovascular events after controlling
      for traditional risk factors, severity of CHD, statin treatment, cystatin C, and
      N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95%
      confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA2 mass
      compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA2
      activity. After additional adjustment for low-density lipoprotein (LDL), the HRs
      were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity:
      1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer
      statistically significant. CONCLUSIONS: Increased concentrations of Lp-PLA2
      predict future cardiovascular events in patients with manifest CHD independent of
      a variety of potential risk factors including markers of inflammation, renal
      function, and hemodynamic stress.

PMID- 16627804
TI  - Fibrin and activated platelets cooperatively guide stem cells to a vascular
      injury and promote differentiation towards an endothelial cell phenotype.
AB  - OBJECTIVE: Bone marrow-derived progenitor cells play a role in vascular
      regeneration. However, their homing to areas of vascular injury is poorly
      understood. One of the earliest responses to an injury is the activation of
      coagulation and platelets. In this study we assessed the role of hemostatic
      components in the recruitment of CD34+ cells to sites of injury. METHODS AND
      RESULTS: Using an ex vivo injury model, representing endothelial cell (EC) injury
      or vessel denudation, we studied homing of CD34+ under flow. Platelet aggregates
      facilitated initial tethering and rolling of CD34+ cells through interaction of P
      selectin expressed by platelets and P-selectin glycoprotein ligand-1 (PSGL-1),
      expressed by CD34+ cells. Ligation of PSGL-1 activated adhesion molecules on
      CD34+ cells, ultimately leading to firm adhesion of CD34+ cells to tissue factor
      expressing ECs or to fibrin-containing thrombi formed on subendothelium. We also
      demonstrate that fibrin-containing thrombi can support migration of CD34+ cells
      to the site of injury and subsequent differentiation toward a mature EC
      phenotype. Additionally, intravenously injected CD34+ cells homed in vivo to
      denuded arteries in the presence of endogenous leukocytes. CONCLUSIONS: We
      provide evidence that hemostatic factors, associated with vascular injury,
      provide a regulatory microenvironment for re-endothelialization mediated by
      circulating progenitor cells.

PMID- 16627805
TI  - Degenerative aortic valve stenosis, but not coronary disease, is associated with
      shorter telomere length in the elderly.
AB  - OBJECTIVE: The mechanisms responsible for the age-related increase in the
      incidence of calcific aortic valve stenosis (CAS) are unclear but may include
      telomere-driven cellular senescence. Because telomere length varies widely among
      individuals of the same age, we hypothesized that patients with shorter telomeres
      would be prone to develop CAS late in life. METHODS AND RESULTS: Mean telomere
      length was measured in leukocytes from a cohort of 193 patients > or =70 years of
      age with and without CAS. Pilot experiments performed in 30 patients with CAS and
      controls pair-matched for age, sex, and presence or absence of coronary disease
      demonstrated significantly shorter telomeres in the CAS group both by Southern
      blot hybridization (5.75+/-0.55 kbp versus 6.27+/-0.7 kbp, P=0.0023) and by a
      quantitative polymerase chain reaction-based technique (relative telomere length
      0.88+/-0.19 versus 1.0+/-0.19, P=0.01). This finding was then confirmed in the
      whole cohort (CAS n=64, controls n=129, relative telomere length=0.86+/-0.16
      versus 0.94+/-0.12, P=0.0003). Both groups were comparable for potential
      confounding characteristics. Subgroup analysis according to the presence or
      absence of coronary disease demonstrated no association of this disorder with
      telomere length. CONCLUSIONS: In the elderly, calcific aortic stenosis, but not
      coronary disease, is associated with shorter leukocyte telomere length.

PMID- 16627806
TI  - Coronary atherosclerosis and alcohol consumption: angiographic and mortality
      data.
AB  - OBJECTIVE: Moderate alcohol consumption is associated with reduced cardiovascular
      disease (CVD) risk. Whether this protection is based on a lesser degree of
      coronary atherosclerosis has not been established. METHODS AND RESULTS: We
      studied 1676 men and 465 women consecutively undergoing coronary angiography. A
      score (ATS) was calculated by summing the percent lumen narrowing of all main
      vessels; alcohol consumption was quantitated by questionnaire. In univariate
      analysis, ATS was significantly (P< or = 0.001) associated with male sex, age,
      familial CVD, smoking, diabetes, hypertension, and serum cholesterol levels;
      alcohol consumption was associated with less frequent diabetes (P<0.001) and
      lower ATS (P = 0.02). By multivariate analysis, alcohol intake was associated
      with lower ATS (P<0.01) independently of the other risk factors; the estimated
      effect size was comparable to that associated with a 1-mmol decrement in serum
      cholesterol. Over a median follow-up of 93 months, 37 women and 194 men died from
      a cardiac cause. By Cox analysis, positive predictors for cardiac mortality were
      male sex (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1 to 2.6]), age
      (HR, 2.1; 95% CI, 1.8 to 2.5 per decade) and diabetes (HR, 1.7; 95% CI, 1.2 to
      2.4), whereas alcohol consumption was the only negative predictor (HR, 0.84; 95%
      CI, 0.71 to 1.00). CONCLUSIONS: In a selected high-risk population, moderate
      alcohol consumption was independently associated with less coronary
      atherosclerosis and lower risk for cardiac mortality.

PMID- 16627807
TI  - New insights to vascular smooth muscle cell and pericyte differentiation of mouse
      embryonic stem cells in vitro.
AB  - OBJECTIVE: The molecular mechanisms that regulate pericyte differentiation are
      not well understood, partly because of the lack of well-characterized in vitro
      systems that model this process. In this article, we develop a mouse embryonic
      stem (ES) cell-based angiogenesis/vasculogenesis assay and characterize the
      system for vascular smooth muscle cell (VSMC) and pericyte differentiation.
      METHODS AND RESULTS: ES cells that were cultured for 5 days on OP9 stroma cells
      upregulated their transcription of VSMC and pericyte selective genes. Other SMC
      marker genes were induced at a later time point, which suggests that vascular
      SMC/pericyte genes are regulated by a separate mechanism. Moreover, sequence
      analysis failed to identify any conserved CArG elements in the vascular SMC and
      pericyte gene promoters, which indicates that serum response factor is not
      involved in their regulation. Gleevec, a tyrosine kinase inhibitor that blocks
      platelet-derived growth factor (PDGF) spell-receptor signaling, and a
      neutralizing antibody against transforming growth factor (TGF) beta1, beta2, and
      beta3 failed to inhibit the induction of vascular SMC/pericyte genes. Finally, ES
      derived vascular sprouts recruited cocultured MEF cells to pericyte-typical
      locations. The recruited cells activated expression of a VSMC- and pericyte
      specific reporter gene. CONCLUSIONS: We conclude that OP9 stroma cells induce
      pericyte differentiation of cocultured mouse ES cells. The induction of pericyte
      marker genes is temporally separated from the induction of SMC genes and does not
      require platelet-derived growth factor B or TGFbeta1 signaling.

PMID- 16627808
TI  - Human paraoxonase-1 overexpression inhibits atherosclerosis in a mouse model of
      metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome is typified by obesity, dyslipidemia,
      diabetes, hypertension, increased oxidative stress, and accelerated
      atherosclerosis. Paraoxonase1 (PON1), a high-density lipoprotein (HDL)-associated
      antioxidant enzyme that prevents the oxidation of low-density lipoprotein (LDL),
      is low in the metabolic syndrome. METHODS AND RESULTS: We used adenovirus
      mediated PON1 gene transfer (AdPON1) to overexpress human PON1 in mice with
      combined leptin and LDL receptor deficiency, a model of metabolic syndrome. PON1
      activity, plasma lipids, the titer of autoantibodies against malondialdehyde
      (MDA)-modified LDL, and atherosclerosis in AdPON1 mice were compared with these
      in mice that received a control recombinant adenovirus (AdRR5). PON1 activity was
      increased 4.4-fold (P<0.001) in AdPON1 mice (N = 12), whereas in AdRR5 mice (N =
      11) activity did not change. Expressing human PON1 significantly reduced the
      total plaque volume, the volume of plaque macrophages, and of plaque-associated
      oxidized LDL. It increased the percentage of smooth muscle cells in the plaques.
      Expressing human PON1 lowered the titer of autoantibodies against MDA-modified
      LDL, a proxy for oxidized LDL in mice. It had no overall effect on plasma total
      cholesterol and triglycerides, as evidenced by the similar area under the curves,
      and on the HDL distribution profile. CONCLUSIONS: Our data suggest that in this
      mouse model of metabolic syndrome, expressing human PON1 inhibited the
      development of atherosclerosis, probably by reducing the amount of oxidized LDL
      in plasma and in the plaque, thereby preventing its proatherogenic effects.
      Adenovirus-mediated gene transfer of human PON1 may be a potential and useful
      tool to prevent/retard atherosclerosis in humans.

PMID- 16627809
TI  - Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to
      label plaque macrophages.
AB  - BACKGROUND: Inflammation within atherosclerotic lesions contributes to plaque
      instability and vulnerability to rupture. We set out to evaluate the use of a
      macrophage labeling agent to identify carotid plaque inflammation by in vivo
      magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty patients with
      symptomatic severe carotid stenosis scheduled for carotid endarterectomy
      underwent multi-sequence MRI of the carotid bifurcation before and after
      injection of ultrasmall superparamagnetic particles of iron oxide (USPIOs). USPIO
      particles accumulated in macrophages in 24 of 30 plaques (80%). Areas of signal
      intensity reduction, corresponding to USPIO/macrophage-positive histological
      sections, were visualized in 24 of 27 (89%) patients, with an average reduction
      in signal intensity induced by the USPIO particles of 24% (range, 3.1% to 60.8%).
      CONCLUSIONS: USPIO-enhanced MRI can identify plaque inflammation in vivo by
      accumulation of USPIO within macrophages in carotid plaques.

PMID- 16627810
TI  - Soluble CD40L levels are regulated by the -3459 A>G polymorphism and predict
      myocardial infarction and the efficacy of antithrombotic treatment in non-ST
      elevation acute coronary syndrome.
AB  - OBJECTIVE: Current evidence suggests the CD40-CD40L pathway as a key process in
      the development, progression, and outcome of acute coronary syndrome (ACS). The
      aim was to investigate the prognostic importance of soluble (s) CD40L levels,
      single nucleotide polymorphisms (SNP) in the CD40LG gene, and the relation
      between sCD40L and SNPs in patients with acute coronary syndromes (ACS). METHODS
      AND RESULTS: Samples were obtained on admission from 2359 patients with non-ST
      elevation ACS randomized to an early invasive versus a conservative and to
      placebo controlled long-term dalteparin treatment in the FRISC-II study. The 
      3459 A>G SNP was identified as a novel regulator of sCD40L levels (P = 0.001). In
      the placebo-treated group, sCD40L levels above median were associated with a 2.5
      fold increased risk of myocardial infarction (MI) (P < or = 0.001) but not with
      raised mortality. In the dalteparin treated group, sCD40L showed no association
      with MI (P = 0.75). Consequently, dalteparin treatment was effective in reducing
      the risk of MI only in patients with sCD40L levels above median. A combined
      assessment of troponin-T and sCD40L complemented the prognostic information on
      risk of MI. CONCLUSIONS: We identified a SNP in the CD40LG gene as a novel
      regulator of sCD40L plasma concentrations. Soluble CD40L levels above median
      reflect a prothrombotic state, which can be managed with the use of intense anti
      thrombotic treatments.

PMID- 16627811
TI  - Identification of a novel C5L2 variant (S323I) in a French Canadian family with
      familial combined hyperlipemia.
AB  - OBJECTIVE: A functional acylation stimulating protein (ASP) receptor, C5L2, has
      been recently identified in ASP-responsive cells. Impaired ASP-mediated
      triglyceride synthesis has previously been described in a subset of
      hyperapolipoprotein B/familial combined hyperlipidemia subjects. METHODS AND
      RESULTS: DNA sequencing of C5L2 coding region in 61 unrelated probands identified
      a heterozygous variant (G968-->T) in 1 subject, resulting in Ser323-->Ile
      substitution in the carboxyl terminal region. This variant was not detected in
      2176 additional chromosomes by restriction fragment length polymorphism or
      fluorescence polarization genotyping. Eight family members of the proband were
      identified with one altered (+/-)C5L2 allele. Nine other family members had the
      wild-type (+/+)C5L2 sequence. The abnormal allele was associated with increased
      plasma triglyceride, plasma cholesterol, low-density lipoprotein (LDL)
      cholesterol, apolipoprotein B and ASP. Of 23 subjects tested in cell-based ASP
      bioactivity assays, those with C5L2(+/-) variant (n = 2) had a 50% reduction in
      ASP-stimulated triglyceride synthesis, glucose transport and marked reduction in
      maximal binding (B(max)). By contrast, a C5L2(+/+) family member responded
      normally, as did hyperapolipoprotein B normal ASP subjects compared with
      C5L2(+/+) controls (n = 6). CONCLUSIONS: The S323I variant may alter C5L2
      function and might be one molecular basis contributing to familial combined
      hyperlipidemia.

PMID- 16627812
TI  - T cell costimulation in the development of cardiac allograft vasculopathy:
      potential targets for therapeutic interventions.
AB  - Cardiac allograft vasculopathy (CAV) is a form of coronary arterial stenosis and
      a leading cause of death in patients who survive beyond the first year after
      heart transplantation. Histopathologically, this lesion is concentric diffuse
      intimal hyperplasia of the arterial wall that is accompanied by extensive
      infiltration of inflammatory cells, including T cells. Many studies have explored
      the potential risk factors related to this arterial lesion and its pathogenesis.
      Continuous minor endothelial cell damage evokes inflammatory processes including
      T cell activation. Costimulatory molecules play crucial roles in this T cell
      activation. Many costimulatory pathways have been described, and some are
      involved in the pathogenesis of CAV, atherogenesis, and subsequent plaque
      formation. In this review, we summarize the present knowledge of the role of
      these pathways in CAV development and the possibility of manipulating these
      pathways as a means to treat heart allograft vascular disease and
      atherosclerosis.

PMID- 16627813
TI  - Nonpharmacological treatment of hypercholesterolemia increases circulating
      endothelial progenitor cell population in adults.

PMID- 16627814
TI  - Platelet-activating factor acetylhydrolase concentration in children with
      abdominal obesity.

PMID- 16627818
TI  - COX-2 in cardiovascular disease.

PMID- 16627819
TI  - Where is endothelial nitric oxide synthase more critical: plasma membrane or
      Golgi?

PMID- 16627820
TI  - Flow perturbation is linked to endothelial par signaling.

PMID- 16627821
TI  - A new dimension in the vasculoprotective function of HDL: progenitor-mediated
      endothelium repair.

PMID- 16627822
TI  - Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of
      weight loss.
AB  - Obesity is becoming a global epidemic in both children and adults, and it is
      associated with numerous co-morbidities such as cardiovascular diseases (CVD),
      type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered
      breathing. In fact, is an independent risk factor for CVD and CVD risks have been
      also documented in obese children, and is associated with reduced life
      expectancy. A variety of adaptations/alterations in cardiac structure and
      function occur in the individual as adipose tissue accumulates in excess amount.
      As a whole, overweight/obesity predispose or is associated with numerous cardiac
      complications such as coronary heart disease, heart failure, and sudden death
      through its impact on the cardiovascular system.

PMID- 16627824
TI  - Phosphorylated HSP27 modulates the association of phosphorylated caldesmon with
      tropomyosin in colonic smooth muscle.
AB  - Thin-filament regulation of smooth muscle contraction involves phosphorylation,
      association, and dissociation of contractile proteins in response to agonist
      stimulation. Phosphorylation of caldesmon weakens its association with actin
      leading to actomyosin interaction and contraction. Present data from colonic
      smooth muscle cells indicate that acetylcholine induced a significant association
      of caldesmon with PKCalpha and sustained phosphorylation of caldesmon at ser789.
      Furthermore, acetylcholine induced significant and sustained increase in the
      association of phospho-caldesmon with heat-shock protein (HSP)27 with concomitant
      increase in the dissociation of phospho-caldesmon from tropomyosin. At the thin
      filament level, HSP27 plays a crucial role in acetylcholine-induced association
      of contractile proteins. Present data from colonic smooth muscle cells
      transfected with non-phospho-HSP27 mutant cDNA indicate that the absence of
      phospho-HSP27 inhibits acetylcholine-induced caldesmon phosphorylation. Our
      results further indicate that the presence of phospho-HSP27 significantly
      enhances acetylcholine-induced sustained association of phospho-caldesmon with
      HSP27 with a concomitant increase in acetylcholine-induced dissociation of
      phospho-caldesmon from tropomyosin. We thus propose a model whereby upon
      acetylcholine-induced phosphorylation of caldesmon at ser789, the association of
      phospho-caldesmon (ser789) with phospho-HSP27 results in an essential
      conformational change leading to dissociation of phospho-caldesmon from
      tropomyosin. This leads to the sliding of tropomyosin on actin thus exposing the
      myosin binding sites on actin for actomyosin interaction.

PMID- 16627825
TI  - Different roles for human lung dendritic cell subsets in pulmonary immune defense
      mechanisms.
AB  - Dendritic cells (DC) have a central role in the initiation of adequate immune
      responses. They recognize pathogens by means of Toll-like receptors (TLR) and
      link innate to adaptive immune responses by releasing proinflammatory cytokines
      and inducing T cell proliferation. We conducted this study to evaluate the
      expression and function of TLR on human lung DC subsets and to study their T cell
      stimulatory capacity. TLR gene expression by human pulmonary DC was evaluated by
      RT-PCR, while protein expression was analyzed by flow cytometry. We investigated
      cytokine release by DC in response to different TLR ligands. T cell stimulatory
      capacity was evaluated by mixed leukocyte reactions of purified lung DC with
      allogeneic T cells. Myeloid dendritic cells type 1 (mDC1) and myeloid dendritic
      cells type 2 (mDC2) express mRNA transcripts for TLR1, TLR2, TLR3, TLR4, TLR6,
      and TLR8. Flow cytometric analysis demonstrated high TLR2 protein expression for
      mDC1 and moderate TLR4 expression for mDC2. mDC1 and mDC2 release proinflammatory
      cytokines (TNF-alpha, IL-1beta, IL-6, and IL-8) in response to TLR2 and TLR4
      ligands. TLR3 ligands induce cytokine release in mDC1, but not in mDC2.
      Plasmacytoid DC (pDC) express TLR7 and TLR9 and release proinflammatory cytokines
      in response to imiquimod and IFN-alpha in response to CpG oligonucleotides. mDC1
      are strong inducers of T cell proliferation, while pDC hardly induce any T cell
      proliferation. mDC2 have an intermediate T cell-stimulatory capacity. Our results
      show divergent roles for the different human lung DC subsets, both in innate and
      adaptive immune responses.

PMID- 16627826
TI  - A case of self-inflicted craniocerebral penetrating injury.

PMID- 16627827
TI  - Proximal tibiofibular dislocation.
AB  - Proximal tibiofibular joint dislocation is an uncommon injury, which may be
      easily missed on plain radiography. If recognised, it can be treated in the
      emergency department, avoiding surgery and long term problems. The case is
      presented of a 22 year old male rugby player who was tackled from the left hand
      side while turning to the left. He heard a "pop" from his knee as he fell to the
      ground. Clinical examination revealed a prominence in the area of the fibular
      head. There was no evidence of peroneal nerve injury. Plain x rays confirmed a
      clinical suspicion for anterior dislocation of the proximal tibiofibular joint.
      Proximal tibiofibular joint dislocation typically occurs when the knee is
      slightly flexed and the foot is rotated and plantar flexed. Antero lateral
      dislocation is the most common pattern. Diagnosis is largely clinical, but the
      findings may be subtle. Plain films may not show any abnormality and computed
      tomography is the investigation of choice if there is clinical suspicion for the
      injury. The dislocation should be reduced in the emergency department, but
      controversy exists whether early mobilisation or casting is the most appropriate
      course of action.

PMID- 16627828
TI  - Melaena as the presenting symptom of gastric mucosal injury due to blunt
      abdominal trauma.
AB  - Blunt abdominal trauma is a common cause of admission to the typical trauma
      centre. Hollow viscus injury from blunt trauma, however, is unusual and rarely
      involves the stomach. A 15 year old boy sustained a bicycle handle bar injury to
      the abdomen and presented to the casualty department four days later with
      melaena. A computed tomography (CT) scan of the abdomen showed normal findings
      but endoscopy revealed two "kissing" areas of mucosal ulceration on the anterior
      and posterior wall of the gastric antrum. The patient received a blood
      transfusion for anaemia but was otherwise treated conservatively and made a full
      recovery. The authors believe this to be the first reported case of melaena as
      the primary presenting symptom of gastric ulceration secondary to blunt abdominal
      trauma. Diagnosis of hollow viscus injuries due to blunt abdominal trauma
      requires a high index of suspicion and thorough investigation, particularly if
      the presentation is delayed.

PMID- 16627829
TI  - Adopt a disease; make this the year of stroke.

PMID- 16627830
TI  - Paramedics and pre-hospital management of acute myocardial infarction: diagnosis
      and reperfusion.
AB  - In this paper, we discuss and critically analyse pre-hospital management of acute
      myocardial infarction (AMI). It is clear from several large studies that rapid
      diagnosis and application of thrombolysis reduces morbidity and mortality rates.
      Strategies that improve time to treatment in the pre-hospital setting are
      therefore of fundamental importance in the management of this fatal disease. The
      advantage of 12 lead electrocardiography use by paramedics to diagnose AMI and
      reduce time to treatment is discussed. Moreover, paramedic application of
      thrombolysis in the pre-hospital environment is examined. Several studies
      conducted worldwide support the notion that ambulance services can play a role in
      minimising time to treatment for patients with AMI. The contribution of early
      intervention by paramedics trained in critical care is potentially considerable,
      particularly in the important chain of survival that is often initiated by pre
      hospital intervention.

PMID- 16627831
TI  - An experience of emergency ultrasonography in children in a sub-Saharan setting.
AB  - Emergency ultrasonography is an appealing imaging modality in paediatric
      emergencies, given its non-invasive nature and potential as an adjunct to
      physical examination in a setting where rapid decisions need to be made. This
      review of a case series describes the applications, versatility, and limitations
      of emergency physician led ultrasonography in a paediatric resuscitation room in
      a sub-Saharan African setting.

PMID- 16627832
TI  - Prospective validation of a current algorithm including bedside US performed by
      emergency physicians for patients with acute flank pain suspected for renal
      colic.
AB  - OBJECTIVE: The purpose of this study was to validate an algorithm recommended by
      current literature for the patients with acute flank pain and evaluate the
      validity of bedside ultrasonography (US) performed by emergency physicians (EP)
      as a part of this algorithm. MATERIALS AND METHODS: This prospective validation
      study was carried out over a 5 month period in a tertiary care hospital adult
      emergency department (ED) with annual attendance of 55,000. Adult patients
      presenting to the ED with unilateral acute flank pain during the study period
      were enrolled into the study consecutively. Oral consent was obtained after the
      protocol was briefly explained to the patient and before the administration of
      analgesia. A protocol form was recorded for each patient enrolled into the study,
      and patients were followed up under the guidance of a previously designated
      algorithm in the ED. Data were analysed with SPSS software. The chi2 test was
      used to compare the dichotomised data of patients, diagnosed with and without
      stones, and to select the significant parameters to be used in the logistic
      regression. RESULTS: Of the 227 patients enrolled, 176 were proven to have
      urinary tract stones. There were 122 patients discharged from ED without further
      investigation except urinalysis and bedside US. Of these 122 directly discharged
      patients, 99 had a urinary stone, and the others did not have a life threatening
      disorder. Four of the 227 patients were admitted to the hospital. The remaining
      51 patients did not have stones detected, and their pain subsided. Having a
      previous history of stones, radiation of pain to the groin, accompanying nausea,
      and detection of pelvicalyceal dilatation using bedside US performed by the EPs
      were found to be the most significant parameters in determining urinary stones in
      logistic regression analysis. Sensitivity and specificity of these parameters
      were: previous history of stones 59% and 66%, radiating pain to the groin 68% and
      49%, nausea 71% and 51%, and detection of pelvicalyceal dilatation by bedside US
      81% and 37%. CONCLUSION: Bedside US performed by EPs could be used safely in the
      evaluation of patients with acute flank pain as a part of a clinical algorithm.
      Previous history of urinary stones, radiation of pain to the groin, accompanying
      nausea. and detection of pelvicalyceal dilatation are major parameters and
      symptoms of urinary stone disease, and could be used in the algorithms.

PMID- 16627833
TI  - Internet health information use and e-mail access by parents attending a
      paediatric emergency department.
AB  - OBJECTIVES: To document internet access and health related usage patterns by
      families of children in a large paediatric emergency department (ED), and to
      discover if parents want the internet to become a tool for transferring medical
      test results. METHODS: This was a pre-tested, 21 item, interview conducted with
      parents at the paediatric ED in Toronto over 3 months. Descriptive statistics and
      frequency distributions were calculated and variables associated with parents
      wishing to access results electronically were examined. RESULTS: In total, 950
      parents completed the interview (93%), of whom 87% reported routine internet
      access, 75% reported having an e-mail account, and 60% accessed their e-mail once
      or more a day. Over half (56%) reported searching the internet for health related
      information, with 8.5% of these searching immediately preceding their visit.
      Nearly three quarters (73%) indicated they would like to receive an e-mail
      containing the results of tests conducted in the ED; 66% of all respondents and
      89% of those with e-mail indicated that they would like their child's primary
      care provider to receive information electronically. CONCLUSION: The majority of
      families have internet access and most want to receive medical information
      electronically and to send it to the primary provider. The vast use of internet
      for health related information emphasises the need to guide parents regarding
      reliable resources online, possibly as part of their ED visit.

PMID- 16627834
TI  - Paediatric emergency department staff perceptions of infection control measures
      against severe acute respiratory syndrome.
AB  - OBJECTIVES: To determine paediatric emergency department (ED) staff perceptions
      of the effectiveness and practice of infection control measures against a novel
      virulent pathogen. METHODS: All medical staff of the paediatric ED in a tertiary
      medical centre completed a written questionnaire near the onset of the severe
      acute respiratory syndrome (SARS) outbreak. Level of concern regarding SARS, and
      perceptions of effectiveness and use of infection control measures were assessed
      on a 5 point scale. Statistical analysis was performed using chi2 test and one
      way analysis of variance with significance at p<0.05. RESULTS: Response rate was
      97% (116/120). All scores were given out of 5 possible points. Using isolation
      rooms (mean score 4.6), wearing a mask when examining patients (4.5), and
      handwashing (4.5) were considered most effective. Staff physicians reported
      handwashing more than nurses and trainees (4.9 v 4.5 and 4.5, respectively;
      p<0.05) while other measures were reported equally. Respondents considering SARS
      a high public health threat reported higher compliance with handwashing (4.8 v
      4.4), always wearing a mask (3.9 vs 3.2) and gloves (3.6 v 2.9) in the ED
      (p<0.05), but not eye protection (3.4 v 3.0), gown use (4.9 v 4.7), or wearing a
      mask when examining patients (5.0 v 4.8). Staff who considered combined infection
      control measures effective in protecting patients and healthcare workers did not
      report increased compliance. CONCLUSIONS: Eye protection was perceived as only
      moderately effective in protecting against the spread of SARS, and reported
      compliance was relatively poor among ED staff. Concern of SARS as a public health
      threat rather than perceived effectiveness of infection control measures appears
      to have a greater impact on compliance.

PMID- 16627835
TI  - How do clinical features help identify paediatric patients with fractures
      following blunt wrist trauma?
AB  - OBJECTIVE: Wrist injuries are a common presentation to the emergency department
      (ED). There are no validated decision rules to help clinicians evaluate
      paediatric wrist trauma. This study aimed to identify which clinical features are
      diagnostically useful in deciding the need for a wrist radiograph, and then to
      develop a clinical decision rule. METHODS: This prospective cohort study was
      carried out in the ED of Sheffield Children's Hospital. Eligible patients were
      recruited if presenting within 72 hours following blunt wrist trauma. A
      standardised data collection form was completed for all patients. The outcome
      measure was the presence or absence of a fracture. Univariate analysis was
      performed with the chi2 test. Associated variables (p<0.2) were entered into a
      multivariate model. Classification and regression tree (CART) analysis was used
      to derive the clinical decision rule. RESULTS: In total, 227 patients were
      recruited and 106 children were diagnosed with fractures (47%). Of 10 clinical
      features analysed, six were found by univariate analysis to be associated with a
      fracture. CART analysis identified the presence of radial tenderness, focal
      swelling, or an abnormal supination/pronation as the best discriminatory
      features. Cross fold validation of this decision rule had a sensitivity of 99.1%
      (95% confidence interval 94.8% to 100%) and a specificity of 24.0% (17.2% to
      32.3%). The radiography rate would be 87%. CONCLUSIONS: Radial tenderness, focal
      swelling, and abnormal supination/pronation are associated with wrist fractures
      in children. The clinical decision rule derived from these features had a high
      sensitivity, but low specificity, and would not substantially alter our current
      radiography rate. The potential for a clinical decision rule for paediatric wrist
      trauma appears limited.

PMID- 16627836
TI  - Comparison of nebulised magnesium sulphate and salbutamol combined with
      salbutamol alone in the treatment of acute bronchial asthma: a randomised study.
AB  - OBJECTIVE: To test the hypothesis that combined administration of multiple doses
      of nebulised salbutamol and magnesium sulphate provides additional benefit
      compared with salbutamol alone in adult patients with acute asthma. DESIGN:
      Randomised, double blind, prospective study. METHODS: A total of 100 patients
      presenting to an emergency department with an acute attack of bronchial asthma
      were randomised to two groups: nebulisation with a combination of salbutamol and
      magnesium sulphate (group A) and nebulisation with salbutamol only (group B).
      Both groups received nebulisation thrice at intervals of 20 minutes. Salbutamol
      and magnesium sulphate were administered in doses of 0.5 mg and 500 mg,
      respectively, and the solutions were made isotonic to plasma osmolality. Pulse
      rate, blood pressure, and peak expiratory flow rate (PEFR) were measured at
      baseline and at 15, 60, 75, and 120 minutes. Serum magnesium levels and blood
      gases were measured at 0 and 120 minutes in both groups. RESULTS: All patients
      had either acute severe or life threatening asthma. The baseline characteristics
      were comparable in the two groups. Both groups showed significant rise in PEFR at
      all time intervals, however, there was no significant difference between the
      groups in rise in PEFR at any time point. Serum magnesium levels remained within
      normal limits, and there was no difference in requirement of additional
      medication during the study or hospital admission rates in both groups. No
      significant side effects were noted. CONCLUSION: This study suggests that there
      is no therapeutic benefit of adding magnesium sulphate to salbutamol nebulisation
      in the treatment of patients with acute severe or life threatening asthma.

PMID- 16627837
TI  - Emergency department census of patients awaiting admission following
      reorganisation of an admissions process.
AB  - OBJECTIVES: To determine the impact of reorganisation of an acute admissions
      process on numbers of people in the emergency department (ED) awaiting admission
      to a hospital bed in a major teaching hospital. METHODS: We studied all emergency
      medical patients admitted to St James' Hospital, Dublin, between 1 January 2002
      and 31 December 2004. In 2002, patients were admitted to a variety of wards from
      the ED when a hospital bed became available. In 2003, two centrally located wards
      were reconfigured to function as an acute medical admissions unit (AMAU) (bed
      capacity 59), and all emergency patients were admitted directly to this unit from
      the ED (average 15 admissions per day). The maximum permitted length of stay on
      the AMAU was 5 days. We recorded the number of patients in the ED, who were
      awaiting the availability of a hospital bed, at 0700 and 1700 on the days of
      recording during the 36 month study period. RESULTS: The impact of the AMAU
      reduced overall hospital length of stay from 7 days in 2002 to 5 days in 2003 and
      2004 (p<0.0001). The median number of patients waiting in the ED for a hospital
      bed reduced from 14 in 2002 to 9 in 2003 and 8 in 2004 (p<0.0001). While age and
      sex of patients did not differ over the years, the factors that independently
      contributed to the number of patients awaiting admission were the day of the
      week, the month of the year, and and the extent of the comorbidity index on the
      previous day's intake (p<0.0001). CONCLUSIONS: This study found that
      reorganisation of a system for acute medical admissions can significantly impact
      on the number of patients awaiting admission to a hospital bed, and allow an ED
      to operate efficiently and at a level of risk acceptable to patients.

PMID- 16627839
TI  - Prediction of mortality among emergency medical admissions.
AB  - BACKGROUND: The Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine
      Score (REMS) are risk adjustment methods for emergency medical admissions
      developed for use in audit, research, and clinical practice. Each predicts in
      hospital mortality using four (RAPS) or six (REMS) variables that can be easily
      recorded at presentation. We aimed to evaluate the predictive value of REMS,
      RAPS, and their constituent variables. METHODS: Age, heart rate, respiratory
      rate, blood pressure, Glasgow Coma Score (GCS) and oxygen saturation were
      recorded for 5583 patients who were transported by emergency ambulance, admitted
      to hospital and then followed up to determine in hospital mortality. The
      discriminant power of each variable, RAPS, and REMS were compared using the area
      under the receiver operator characteristic curve (AROCC). Multivariate analysis
      was used to identify which variables were independent predictors of mortality.
      RESULTS: REMS (AROCC 0.74; 95% CI 0.70 to 0.78) was superior to RAPS (AROCC 0.64;
      95% CI 0.59 to 0.69) as a predictor of in hospital mortality. Although all the
      variables, except blood pressure, were associated with mortality, multivariate
      analysis showed that only age (odds ratio 1.74, p < 0.001), GCS (2.10, p <
      0.001), and oxygen saturation (OR 1.36, p = 0.01) were independent predictors. A
      combination of age, oxygen saturation, and GCS (AROCC 0.80, 95% CI 0.77 to 0.83)
      was superior to REMS in our population. CONCLUSION: REMS is a better predictor of
      mortality in emergency medical admissions than RAPS. Age, GCS, and oxygen
      saturation appear to be the most useful predictor variables. Inclusion of other
      variables in risk adjustment scores, particularly blood pressure, may reduce
      their value.

PMID- 16627838
TI  - The impact of a new regional air ambulance service on a large general hospital.
AB  - BACKGROUND: Helicopter air ambulance crews are influenced in their selection of
      the destination hospital for their patients by several factors including:
      distance from the scene; facilities, on site specialties, and senior cover of the
      receiving hospital; and the proximity of the helicopter landing area to the
      emergency department (ED). Only a limited number of hospitals have landing sites
      adjacent to the ED from which patients can be taken directly into the department
      (primary landing sites). Helicopter crews will often elect to over fly hospitals
      that do not have primary landing sites because secondary land transfers will add
      delays in delivering patients. Birmingham Heartlands Hospital has an elevated
      helideck adjacent to the ED. In October 2003, the Warwickshire and
      Northamptonshire Air Ambulance (WNAA) service was launched; the hospital sits on
      the western periphery of the area served by the service. METHODS: Prospective
      data was collated on all patients brought by WNAA to Heartlands Hospital between
      1 October 2003 and 31 August 2004. RESULTS: In the 10 month period after the
      launch of the service, the helicopter delivered 83 patients to the ED; 74 of
      these were "off patch". This additional workload generated 163 ward days, 19
      operative procedures, and 85 intensive care unit, high dependency unit, or
      coronary care unit days. The direct costs of this additional workload approached
      160,000 pounds sterling. CONCLUSIONS: In future discussions on the cost
      effectiveness of air ambulances, it will be important to consider both the direct
      and indirect costs to the receiving hospitals arising from the redistribution of
      emergency workload.

PMID- 16627840
TI  - Necessity breeds invention: a study of outpatient management of low velocity
      gunshot wounds.
AB  - BACKGROUND: Since the late 1980s, the emergency department (ED) at the Mater
      Hospital, Belfast, has implemented a policy of treating conservatively patients
      who sustain low velocity gunshot wounds to the lower limbs. Wounds are cleaned
      and minimally debrided under local anaesthetic in the ED. Patients are given oral
      antibiotics, and reviewed 48 hours later at the ED review clinic. OBJECTIVE: To
      investigate the outcome of outpatient ED management of low velocity gunshot
      wounds to the lower limbs. METHOD: This was a retrospective, observational study
      from January 2000 to September 2004 inclusive. Notes were retrieved of those
      patients who had gunshot wound mentioned in the triage text. Patients were
      included if they presented with a low velocity gunshot wound to the lower limbs.
      Demographics and treatment regimen were recorded. RESULTS: In total, 90 patients
      sustained low energy injuries to the lower limb, with 70.5% of wounds involving
      the skin and soft tissue only. Most patients (n = 67) were treated as
      outpatients, which included 80% of unilateral injuries and 46.6% of bilateral
      injuries presented. There were 56 patients reviewed at clinic. Three patients
      developed minor complications CONCLUSION: Irrigation and minimal debridement in
      the outpatient setting is an acceptable method of treatment for low energy
      gunshot wounds to the lower limbs, without orthopaedic or vascular involvement.

PMID- 16627841
TI  - Effect of population ageing on emergency department speed and efficiency: a
      historical perspective from a district general hospital in the UK.
AB  - OBJECTIVE: To examine changes in the rate of seeing patients between 1990 and
      2004 and to see whether performance might be related to patient age, using data
      held on the patient administration system. METHOD: Data collected in 1990 were
      compared with those collected in 2004. Age related data were examined for the
      following parameters: the number of patients arriving by ambulance; the time
      taken to process the attendance; the number of investigations; the number of
      emergency admissions; and the length of inpatient stay. RESULTS: Emergency
      department (ED) performance has fallen markedly since 1990. Between 1990 and
      2004, there was a 54% increase in total patients with a disproportionate 198%
      increase in patients aged more than 70 years, including a 671% increase in those
      aged more than 90 years. The time taken to manage patients increased with age. In
      2004, there was a marked rise in investigation rates, and the probability of
      having investigations increased with age. In 2004, older patients (aged more than
      70 years) were 4.9 times more likely to require admission to hospital than
      younger patients (aged 30 years or less). Their average length of stay was 6.9
      times longer. Younger patients were 3.3 times more numerous than older patients
      but older patients occupied 9.8 times more emergency bed days. CONCLUSIONS:
      Pressure on emergency care is associated with a disproportionate increase in the
      number of elderly patients and with an increased tendency to investigate them.
      Population ageing is of central importance in planning health services.

PMID- 16627842
TI  - Effect of an extended scope physiotherapy service on patient satisfaction and the
      outcome of soft tissue injuries in an adult emergency department.
AB  - OBJECTIVES: To evaluate the effect of introducing an extended scope physiotherapy
      (ESP) service on patient satisfaction, and to measure the functional outcome of
      patients with soft tissue injuries attending an adult emergency department (ED),
      comparing management by ESPs, emergency nurse practitioners (ENPs), and all
      grades of ED doctor. METHODS: The ESP service operated on four days out of every
      seven in a week in an urban adult ED. A satisfaction questionnaire was sent to
      all patients with a peripheral soft tissue injury and fractures (not related to
      the ankle) within one week of attending the ED. Patients with a unilateral soft
      tissue ankle injury were sent the acute Short Form 36 (SF-36) functional outcome
      questionnaire, with additional visual analogue scales for pain, at 4 and 16 weeks
      after their ED attendance. Waiting times and time spent with individual
      practitioners was also measured. RESULTS: The ESP service achieved patient
      satisfaction that was superior to either ENPs or doctors. Overall 55% of patients
      seen by the ESP service strongly agreed that they were satisfied with the
      treatment they received, compared with 39% for ENPs and 36% for doctors (p =
      0.048). Assessment of long-term outcome from ankle injury was undermined by poor
      questionnaire return rates. There was a trend towards improved outcomes at four
      weeks in those patients treated by an ESP, but this did not achieve statistical
      significance. CONCLUSION: Adding an ESP service to the interdisciplinary team
      achieves higher levels of patient satisfaction than for either doctors or ENPs.
      Further outcomes research, conducted in a wider range of emergency departments
      and integrated with an economic analysis, is recommended.

PMID- 16627843
TI  - Announcing the emergent patient in the emergency department: a randomised trial.
AB  - OBJECTIVE: To determine which of three commonly used methods for notifying
      medical staff of the arrival of an emergent case to the triage area of an
      emergency department (ED) is optimal. METHODS: Prospective, randomised trial.
      Patients arriving with conditions rated as emergencies (triage category 2) were
      randomised to one of three notification arms: by microphone, by telephone, or by
      computer. The proportion of patients seen by a doctor within 10 minutes of
      arrival to the ED in each arm was compared. RESULTS: A total of 1000 patients
      were enrolled. The proportion seen within 10 minutes for patients announced by
      microphone was significantly greater than those announced by telephone or
      computer (67.0% v 63.2% v 57.3%, respectively; chi2 6.30, p = 0.04). No method
      achieved the benchmark proportion of 80% of patients seen within 10 minutes of
      arrival. CONCLUSIONS: A microphone announcement heard by overhead speakers should
      be incorporated with other strategies to improve the timeliness of medical
      assessment of emergent cases.

PMID- 16627844
TI  - A study of childhood attendance at emergency departments in the West Midlands
      region.
AB  - INTRODUCTION: Research into childhood attendance at EDs in the UK has focused
      mainly on injury rather than medical conditions and studies have been relatively
      small. This study looks at all types of ED attendance by children across a large
      population. DATA AND METHODS: Routine data on all new attendances by children
      under 16 years were available for 12 EDs in the West Midlands (period: 1 April
      2002 to 31 March 2004, 365 695 records). The data were split into four age groups
      (<1, 1-4, 5-9, and 10-15 years). RESULTS: Injury related conditions increased
      with age (with the exception of head injury). Respiratory and gastrointestinal
      were the most common medical conditions decreased with age. 11.5% of children
      were admitted to hospital and this varied from 8.2% (10-15 years) to 24.2% (<1
      year). CONCLUSIONS: This study has shown substantial variations in ED attendance
      by age and has given an insight into the variation among hospitals. This is the
      largest study of childhood ED attendance undertaken in the UK, and it is hoped
      that the questions raised will prompt more research in this field.

PMID- 16627845
TI  - Diagnostic radiopacity and hepatotoxicity following chloroform ingestion: a case
      report.
AB  - BACKGROUND: Diagnostic imaging can help in the management of toxicologic
      emergencies. The authors report on a patient who presented to the emergency
      department with coma and suppressed respirations after ingestion of an unknown
      substance. METHODS: Ingestion of chloroform with radiopaque material in the bowel
      on abdominal radiograph was documented. The patient was treated with
      haemoperfusion, activated charcoal, and laxatives to decrease the toxicities.
      RESULTS: Hepatotoxicity occurred on post-ingestion day 3 and elevation of liver
      enzymes reached peak levels on post-ingestion day 5. The patient received N
      acetylsystein and supportive care during hospitalisation. The patient improved
      from hepatic dysfunction and was discharged without complication on post
      ingestion day 11. CONCLUSION: Radiographic studies in toxicology may confirm a
      diagnosis and assist in therapeutic intervention.

PMID- 16627846
TI  - A risk assessment based approach to the management of acute poisoning.
AB  - Early assessment and management of poisoning constitutes a core emergency
      medicine competency. Medical and psychiatric emergencies coexist; the acute
      poisoning is a dynamic medical illness that represents an acute exacerbation of a
      chronic underlying psychosocial disorder. The emergency physician must use an
      approach that ensures early decisions address potentially time critical
      interventions, while allowing management to be tailored to the individual
      patient's needs in that particular medical setting. This article outlines a
      rationale approach to the management of the poisoned patient that emphasises the
      importance of early risk assessment. Ideally, this approach should be used in the
      setting of a health system designed to optimise the medical and psychosocial care
      of the poisoned patient.

PMID- 16627847
TI  - Best evidence topic report. The use of intravenous terlipressin in non-variceal
      upper GI bleeds.
AB  - A short cut review was carried out to establish whether terlipressin should be
      used in upper GI bleeding when variceal bleeding is not suspected as the cause.
      556 papers were found, of which none answered the three part question. The
      clinical bottom line is that there is no evidence for the use of intravenous
      terlipressin in patients presenting with acute, severe upper GI bleeds unless
      they have endoscopic evidence of varices or a high clinical index of suspicion is
      met.

PMID- 16627849
TI  - Best evidence topic report. Ultrasound placement of needle in three-in-one nerve
      block.
AB  - A short cut review was carried out to establish whether ultrasound placement of
      three-in-one block is better than placement using a nerve stimulator. 137 papers
      were found, of which two presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these best papers
      are tabulated. The clinical bottom line is that ultrasound guidance is better
      than electrical nerve stimulation at obtaining a good quality three in one
      femoral block.

PMID- 16627850
TI  - Best evidence topic report. Beta-Blockers in cocaine induced acute coronary
      syndrome.
AB  - A short cut review was carried out to establish whether beta blockers should be
      used in the treatment of chest pain associated with cocaine use. 12 papers were
      found, of which two presented the best evidence to answer the clinical question.
      The author, date and country of publication, patient group studied, study type,
      relevant outcomes, results and study weaknesses of these best papers are
      tabulated. The clinical bottom line is that Beta Blockers should not be used in
      the treatment of cocaine induced myocardial ischaemia.

PMID- 16627851
TI  - Best evidence topic report. Brain natriuretic peptide as a potential marker of
      acute coronary syndromes.
AB  - A short cut review was carried out to establish whether brain natriuretic peptide
      (BNP) can be used as a marker for acute coronary syndromes. 685 citations were
      found, of which eight presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these best papers
      are tabulated. The clinical bottom line is that BNP shows promise as an early
      cardiac marker and may enhance prognostic stratification. NPV and PPV may be
      unacceptably low to enable use as a sole cardiac marker. Incorporation into a
      multimarker strategy and serial estimations may be necessary.

PMID- 16627852
TI  - Who's who at a major incident: standardising role titles for emergency planners.
AB  - OBJECTIVE: To standardise the names for key roles in a major incident. METHODS: A
      Delphi study using experts in major incident planning. RESULTS: There is clear
      consensus regarding the need for standard nomenclature. The expert group
      identified 28 roles, and 184 different names were initially given by group
      members for the 28 roles. Agreement on a common nomenclature was achieved in only
      12/28 roles. CONCLUSION: There is agreement for a standardised nomenclature for
      major incident roles. However, consensus may be difficult to achieve from within
      an expert group.

PMID- 16627853
TI  - Case of the month: Unusual presentation of myasthenia gravis with acute
      respiratory failure in the emergency room.
AB  - A 21 year old woman with no past medical history presented to the emergency room
      (ER) with signs and symptoms of sepsis and subsequently went into acute
      respiratory failure. She was found to have myasthenia gravis which was
      exacerbated by the infection. This report highlights the need to consider
      myasthenia gravis in the differential diagnosis of an otherwise unexplained
      respiratory failure in the critical care setting.

PMID- 16627855
TI  - Images in emergency medicine. Lag it.

PMID- 16627856
TI  - Decoding near-threshold perception of fear from distributed single-trial brain
      activation.
AB  - Instead of contrasting functional magnetic resonance imaging (fMRI) signals
      associated with 2 conditions, as customarily done in neuroimaging, we reversed
      the direction of analysis and probed whether brain signals could be used to
      "predict" perceptual states. We probed the neural correlates of perceptual
      decisions by "decoding" brain states during near-threshold fear detection.
      Decoding was attempted by using support vector machines and other related
      techniques. Although previous decoding studies have employed relatively "blocked"
      data, our objective was to probe how the "moment-to-moment" fluctuation in fMRI
      signals across a population of voxels reflected the participant's perceptual
      decision. Accuracy increased from when 1 region was considered (approximately
      64%) to when 10 regions were used (approximately 78%). When the best
      classifications per subject were averaged, accuracy levels ranged between 74% and
      86% correct. An information theoretic analysis revealed that the information
      carried by pairs of regions reliably exceeded the sum of the information carried
      by individual regions, suggesting that information was combined "synergistically"
      across regions. Our results indicate that the representation of behavioral choice
      is "distributed" across several brain regions. Such distributed encoding may help
      prepare the organism to appropriately handle emotional stimuli and regulate the
      associated emotional response upon the conscious decision that a fearful face is
      present. In addition, the results show that challenging brain states can be
      decoded with high accuracy even when "single-trial" data are employed and suggest
      that multivariate analysis strategies have considerable potential in helping to
      elucidate the neural correlates of visual awareness and the encoding of
      perceptual decisions.

PMID- 16627857
TI  - Insertion of alpha7 nicotinic receptors at neocortical layer V GABAergic synapses
      is induced by a benzodiazepine, midazolam.
AB  - Benzodiazepines act mainly at postsynaptic gamma-aminobutyric acid type A
      (GABA(A)) receptors. In rat neocortical layer V pyramidal neurons, we found that
      midazolam (MDZ), a benzodiazepine, increases the frequency of GABAergic miniature
      inhibitory postsynaptic currents (mIPSCs) via insertion of alpha7 nicotinic
      acetylcholine receptors (nAChRs) at presynaptic GABAergic boutons. Although
      nicotine alone had no effect, MDZ plus nicotine dramatically increased mIPSC
      frequency. Neostigmine, an acetylcholinesterase inhibitor, mimicked the actions
      of nicotine. MDZ increased the number of alpha-bungarotoxin-bound boutons that
      were blocked by protein kinase C (PKC) inhibitors, as revealed by confocal
      imaging of a neuron-synaptic bouton preparation. Thus, MDZ may induce membrane
      translocation of alpha7 nAChRs on GABAergic boutons via activation of PKC,
      enabling endogenous acetylcholine to increase GABA release. The above actions
      seem unique to MDZ because neither other benzodiazepines (diazepam and
      flunitrazepam) nor zolpidem had this effect. The findings reveal both a novel
      cholinergic modulatory mechanism affecting GABAergic transmission and a novel
      action of some general anesthetics.

PMID- 16627858
TI  - Differences in cyclin D2 and D1 protein expression distinguish forebrain
      progenitor subsets.
AB  - Regulation of neural proliferation is an essential component of brain formation
      and is driven by both intrinsic cell cycle and extrinsic growth and trophic
      molecules. Among the cell cycle proteins, understanding of the relative roles of
      the G1-phase active cyclins D2 and D1 (cD2 and cD1) has been hampered by lack of
      data regarding their expression patterns. In this study, cD2 immunoreactivity was
      examined in the neocortex, ganglionic eminences/striatum, and hippocampal
      formation from embryonic day 12.5 until postnatal day 60 to more precisely
      characterize the expression of this protein during forebrain development. The
      localization of cD1 was also immunohistologically mapped for comparison.
      Throughout forebrain development, both overlapping and nonoverlapping protein
      expression of these cyclins suggests the presence of shared and unique cell cycle
      requirements for neurogenesis that distinguishes progenitor pools.

PMID- 16627859
TI  - White matter pathway asymmetry underlies functional lateralization.
AB  - Structural and functional asymmetry of the human brain has been well documented
      using techniques such as magnetic resonance imaging (MRI). However, asymmetry of
      underlying white matter connections is less well understood. We applied an MRI
      technique known as diffusion tensor tractography to reveal the morphology of the
      white matter in vivo by mapping directions of maximum water diffusion in brain
      tissue. White matter pathway asymmetry was investigated in a normalized image
      data set of 30 right-handed young healthy individuals. We identified, for the
      first time, a rightwardly asymmetric pathway connecting the posterior temporal
      lobe to the superior parietal lobule. This pathway may be related to auditory
      spatial attention and working memory for which there is evidence for a rightward
      laterality from functional imaging studies. Additional leftward asymmetries
      connecting the parietal and frontal lobes to the temporal lobe may be more
      closely related to laterality of language.

PMID- 16627860
TI  - Maturational changes in the interdependencies between cortical brain areas of
      neonates during sleep.
AB  - This work aims at assessing the maturational changes in the interdependence
      between the activities of different cortical areas in neonates during active
      sleep (AS) and quiet sleep (QS). Eight electroencephalography (EEG) channels were
      recorded in 3 groups of neonates of increasing postmenstrual age. The average
      linear (AVL) and average nonlinear (AVN) interdependencies of each electrode
      region with the remaining ones were calculated using the coherence function and a
      recently developed index of nonlinear coupling between 2 signals in their state
      spaces, respectively. In theta band, AVL increased with neonate's age for central
      and temporal regions during QS. In beta band, AVL increased for most cortical
      regions during QS and a parallel decrease of AVL with neonate's age was found
      during AS. For all regions, beta AVL was greater in AS than in QS in preterm
      neonates but the reverse happened in older term neonates. Contrarily to AVL, AVN
      decreased with age during QS for most cortical regions. Surrogate data test
      showed that the interdependencies were nonlinear in preterm and younger term
      neonates but in older term both linear and nonlinear interdependencies coexisted.
      It is concluded that neonatal maturation is associated with changes in the
      magnitude and character of the EEG interdependencies during sleep.

PMID- 16627861
TI  - Neuroplasticity in human callosal dysgenesis: a diffusion tensor imaging study.
AB  - Callosal dysgenesis (CD) is observed in many neurodevelopmental conditions, but
      its subjacent mechanisms are unknown, despite extensive research on animals. Here
      we employ magnetic resonance diffusion tensor imaging and tractography in human
      CD to reveal the aberrant circuitry of these brains. We searched particularly for
      evidence of plasticity. Four main findings are described--1) in the presence of a
      callosal remnant or a hypoplastic corpus callosum (CC), fibers therein largely
      connect the expected neocortical regions; 2) callosal remnants and hypoplastic
      CCs display a fiber topography similar to normal; 3) at least 2 long abnormal
      tracts are formed in patients with defective CC: the well-known Probst bundle
      (PB) and a so far unknown sigmoid, asymmetrical aberrant bundle connecting the
      frontal lobe with the contralateral occipitoparietal cortex; and 4) whereas the
      PB is topographically organized and has an ipsilateral U-connectivity, the
      sigmoid bundle is a long, heterotopic commissural tract. These observations
      suggest that when the developing human brain is confronted with factors that
      hamper CC fibers to cross the midline, some properties of the miswired fibers are
      maintained (such as side-by-side topography), whereas others are dramatically
      changed, leading to the formation of grossly abnormal white matter tracts.

PMID- 16627862
TI  - Noninvasive ventilation improves preoxygenation before intubation of hypoxic
      patients.
AB  - RATIONALE: Critically ill patients are predisposed to oxyhemoglobin desaturation
      during intubation. OBJECTIVES: To find out whether noninvasive ventilation (NIV),
      as a preoxygenation method, is more effective at reducing arterial oxyhemoglobin
      desaturation than usual preoxygenation during orotracheal intubation in
      hypoxemic, critically ill patients. METHODS: Prospective randomized study
      performed in two surgical/medical intensive care units (ICUs). Preoxygenation was
      performed, before a rapid sequence intubation, for a 3-min period using a
      nonrebreather bag-valve mask (control group) or pressure support ventilation
      delivered by an ICU ventilator through a face mask (NIV group) according to the
      randomization. MEASUREMENTS AND MAIN RESULTS: The control (n = 26) and NIV (n =
      27) groups were similar in terms of age, disease severity, diagnosis at
      admission, and pulse oxymetry values (Sp(O(2))) before preoxygenation. At the end
      of preoxygenation, Sp(O(2)) was higher in the NIV group as compared with the
      control group (98 +/- 2 vs. 93 +/- 6%, p < 0.001). During the intubation
      procedure, the lower Sp(O(2)) values were observed in the control group (81 +/-
      15 vs. 93 +/- 8%, p < 0.001). Twelve (46%) patients in the control group and two
      (7%) in the NIV group had an Sp(O(2)) below 80% (p < 0.01). Five minutes after
      intubation, Sp(O(2)) values were still better in the NIV group as compared with
      the control group (98 +/- 2 vs. 94 +/- 6%, p < 0.01). Regurgitations (n = 3; 6%)
      and new infiltrates on post-procedure chest X ray (n = 4; 8%) were observed with
      no significant difference between groups. CONCLUSION: For the intubation of
      hypoxemic patients, preoxygenation using NIV is more effective at reducing
      arterial oxyhemoglobin desaturation than the usual method.

PMID- 16627863
TI  - Inhaled L-arginine improves exhaled nitric oxide and pulmonary function in
      patients with cystic fibrosis.
AB  - RATIONALE: Nitric oxide formation is deficient in airways of patients with cystic
      fibrosis (CF). Since nitric oxide has bronchodilatory effects, nitric oxide
      deficiency may contribute to airway obstruction in CF. OBJECTIVES: We reasoned
      that inhalation of l-arginine, the precursor of enzymatic nitric oxide formation,
      could improve airway nitric oxide formation and pulmonary function in patients
      with CF. MEASUREMENTS: Exhaled nitric oxide, pulmonary function, and peripheral
      oxygen saturation were measured before and after a single inhalation of nebulized
      l-arginine solution in patients with CF and in healthy subjects. A saline
      solution of similar osmolarity (1.7%) was used as control. RESULTS: Nebulized l
      arginine not only significantly increased exhaled nitric oxide concentrations but
      also resulted in a sustained improvement of FEV(1) in patients with CF. Oxygen
      saturation also increased significantly after the inhalation of l-arginine.
      Nebulized saline resulted in a small but significant increase in exhaled nitric
      oxide but a decrease in FEV(1) in patients with CF. In control subjects
      inhalation of l-arginine increased exhaled nitric oxide concentrations, but
      FEV(1) decreased. No effect of saline on exhaled nitric oxide, pulmonary
      function, or oxygen saturation was observed in healthy subjects. CONCLUSIONS:
      These data suggest that a single inhalation of l-arginine acutely and transiently
      improves pulmonary function in CF through the formation of nitric oxide.
      Augmentation of airway nitric oxide formation by inhalation of l-arginine is a
      promising therapeutic approach in patients with CF.

PMID- 16627864
TI  - Dobutamine improves liver function after hemorrhagic shock through induction of
      heme oxygenase-1.
AB  - RATIONALE: Induction of heme oxygenase-1 (HO-1) protects the liver against
      reperfusion injury after hemorrhagic shock. Previous data suggest that the
      beta(1)-adrenoceptor agonist dobutamine induces HO-1 in hepatocytes. OBJECTIVES:
      To investigate the functional significance of dobutamine pretreatment for liver
      function after hemorrhagic shock in vivo. METHODS: Anesthetized rats received
      either Ringer's (Vehicle/Shock), 10 microg/kg/min of the beta(1)-adrenoceptor
      agonist dobutamine (Dob/Shock), or 10 microg/kg/min dobutamine and 500
      microg/kg/min of the beta(1)-adrenoceptor antagonist esmolol (Dob/Esmolol/Shock)
      for 6 h. Hemorrhagic shock was induced thereafter (mean arterial pressure, 35 mm
      Hg for 90 min). Animals were resuscitated with shed blood and Ringer's. In
      addition, the HO pathway was blocked after dobutamine pretreatment with 10
      micromol/kg tin-mesoporphyrin-IX (Dob/SnMP/Shock) or animals received 100 mg/kg
      of the carbon monoxide donor dichloromethane (DCM/Shock). MEASUREMENTS:
      Hepatocellular metabolism and liver blood flow were measured by plasma
      disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver
      function. MAIN RESULTS: Pretreatment with dobutamine induced HO-1 in pericentral
      hepatocytes and improved PDR(ICG) (Vehicle/Shock: 11.7 +/- 8.12%/min vs.
      Dob/Shock: 19.7 +/- 2.46%/min, p = 0.006). Blockade of the HO pathway after
      preconditioning and the combined pretreatment with dobutamine and esmolol
      decreased PDR(ICG) (Dob/SnMP/Shock: 12.6 +/- 4.24%/min, p = 0.011;
      Dob/Esmolol/Shock: 10.2 +/- 4.34%/min, p = 0.008). Pretreatment with a carbon
      monoxide donor improved PDR(ICG) (DCM/Shock: 18 +/- 3.19%/min, p = 0.022)
      compared with Vehicle/Shock. CONCLUSIONS: These results suggest a beta(1)
      adrenoceptor-dependent hepatic up-regulation of HO-1 and a better maintained
      hepatocellular function after hemorrhagic shock in animals pretreated with
      dobutamine. The improved hepatocellular function may be in part mediated by
      carbon monoxide because of up-regulation of HO-1. Pretreatment with dobutamine
      might be a potential means of pharmacologic preconditioning before ischemia
      reperfusion of the liver.

PMID- 16627865
TI  - Fluorescein-enhanced autofluorescence thoracoscopy in patients with primary
      spontaneous pneumothorax and normal subjects.
AB  - RATIONALE: The exact site(s) and pathophysiology of air leakage in patients with
      primary spontaneous pneumothorax (PSP) are unknown. In one patient with PSP,
      fluorescein-enhanced autofluorescence thoracoscopy (FEAT) has shown areas of
      parenchymal abnormality unnoticed during white light thoracoscopy (WLT).
      OBJECTIVES: To prospectively perform and compare WLT and FEAT in patients with
      spontaneous pneumothorax and in normal subjects. METHODS: One-time FEAT and WLT
      inspection with systematic mapping of semiquantified lesions in 12 consecutive
      patients with PSP was compared with one-time FEAT and WLT during sequential
      bilateral thoracoscopy in 17 control subjects. RESULTS: WLT abnormalities
      (anthracosis, cobblestone malformation, and blebs/bullae) were more prevalent in
      PSP. FEAT, however, showed high-grade lesions in PSP only, which often were
      present at areas that were normal, or that only showed anthracosis at WLT. When
      blebs/bullae were present, bleb-associated FEAT abnormalities were only present
      in two. Actual fluorescein leakage was seen in two patients with PSP.
      CONCLUSIONS: Lungs in patients with PSP show significantly more abnormalities at
      WLT when compared with normal subjects. High-grade FEAT lesions were exclusively
      present in PSP, and predominantly at lung zones that appeared normal at white
      light inspection. These findings suggest that significant parenchymal
      abnormalities are not limited to lesions visible during WLT, such as blebs and
      bullae.

PMID- 16627866
TI  - Obesity and asthma.
AB  - Asthma and obesity are prevalent disorders, each with a significant public health
      impact, and a large and growing body of literature suggests an association
      between the two. The systemic inflammatory milieu in obesity leads to metabolic
      and cardiovascular complications, but whether this environment alters asthma risk
      or phenotype is not yet known. Animal experiments have evaluated the effects of
      leptin and obesity on airway inflammation in response to both allergic and
      nonallergic exposures and suggest that airway inflammatory response is enhanced
      by both endogenous and exogenous leptin. Cross-sectional and prospective cohort
      studies of humans have shown a modest overall increase in asthma incidence and
      prevalence in the obese, although body mass index does not appear be a
      significant modifier of asthma severity. Studying the obesity-asthma relationship
      in large cohorts, in which self-reports are frequently used to ascertain the
      diagnosis of asthma, has been complicated by alterations in pulmonary physiology
      caused by obesity, which may lead to dyspnea or other respiratory symptoms but do
      not fulfill accepted physiologic criteria for asthma. Recent investigations
      toward elucidating a shared genetic basis for these two disorders have identified
      polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of
      which contains one or more genes encoding receptors relevant to asthma,
      inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor
      gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is
      warranted to synthesize these disparate observations into a cohesive
      understanding of the relationship between obesity and asthma.

PMID- 16627867
TI  - DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer
      dynein arm defects.
AB  - RATIONALE: Primary ciliary dyskinesia (PCD) is characterized by recurrent airway
      infections and randomization of left-right body asymmetry. To date, autosomal
      recessive mutations have only been identified in a small number of patients
      involving DNAI1 and DNAH5, which encode outer dynein arm components. METHODS: We
      screened 109 white PCD families originating from Europe and North America for
      presence of DNAH5 mutations by haplotype analyses and/or sequencing. RESULTS:
      Haplotype analyses excluded linkage in 26 families. In 30 PCD families, we
      identified 33 novel (12 nonsense, 8 frameshift, 5 splicing, and 8 missense
      mutations) and two known DNAH5 mutations. We observed clustering of mutations
      within five exons harboring 27 mutant alleles (52%) of the 52 detected mutant
      alleles. Interestingly, 6 (32%) of 19 PCD families with DNAH5 mutations from
      North America carry the novel founder mutation 10815delT. Electron microscopic
      analyses in 22 patients with PCD with mutations invariably detected outer dynein
      arm ciliary defects. High-resolution immunofluorescence imaging of respiratory
      epithelial cells from eight patients with DNAH5 mutations showed mislocalization
      of mutant DNAH5 and accumulation at the microtubule organizing centers. Mutant
      DNAH5 was absent throughout the ciliary axoneme in seven patients and remained
      detectable in the proximal ciliary axoneme in one patient carrying compound
      heterozygous splicing mutations at the 3'-end (IVS75-2A>T, IVS76+5G>A). In a
      preselected subpopulation with documented outer dynein arm defects (n = 47),
      DNAH5 mutations were identified in 53% of patients. CONCLUSIONS: DNAH5 is
      frequently mutated in patients with PCD exhibiting outer dynein arm defects and
      mutations cluster in five exons.

PMID- 16627868
TI  - Measurement of bronchial and alveolar nitric oxide production in normal children
      and children with asthma.
AB  - RATIONALE: Airway inflammation is characteristic of asthma. Distal inflammation
      may be particularly important. OBJECTIVE: To calculate alveolar nitric oxide (NO)
      concentration (C(alv)) and bronchial flux NO (J(NO)) in children. METHODS: We
      measured C(alv) and J(NO) from the fractional exhaled NO (FeNO(50)) measured at
      multiple exhalation flow rates in 132 children (aged 4-18 yr) with known atopic
      status, medication, and asthma control. MEASUREMENTS AND MAIN RESULTS: Of
      participants, 85% (112/132) completed all measurements. In 20 of 112, the result
      did not fit the linear model. Thus, J(NO) and C(alv) were assessed in 92 (70%)
      subjects. The median (range) values of asthmatic (n = 52), normal (n = 20), and
      nonasthmatic atopic (n = 20) children were as follows: FeNO(50): 28.1 (4.3-190),
      10.35 (3.3-29), 21.8 (8.7-69) ppb, respectively; J(NO): 1,230 (204-9,236), 480
      (196-1,913), 1,225 (486-4,119) pl/s, respectively; C(alv): 2.22 (0.44-6.63), 1.63
      (0.44-3), 1.21 (0.03-2.85) ppb, respectively. A reproducibility study in 18 other
      children gave intraclass correlation coefficients (single measures) of 0.99
      (J(NO)) and 0.81 (C(alv)). J(NO) and C(alv) were higher in children with asthma
      than normal children (p = 0.0004 and p = 0.0002, respectively). Children with
      poorly controlled asthma (n = 27) had higher FeNO(50) measurements than children
      with good symptom control (n = 25): C(alv): mean (+/- SD), 3.17 +/- 1.62 versus
      2.26 +/- 1.30 ppb, p = 0.03; J(NO): mean (+/- SD), 2,634 +/- 2,255 versus 1,193
      +/- 1,294 pl/s, p = 0.007, respectively. CONCLUSIONS: Measurement of J(NO) and
      C(alv) is feasible in 70% of school-age children. FeNO(50) and J(NO) give the
      same information (r = 0.97, p < 0.0001), C(alv) is higher in asthmatic children
      than in normal children and is affected by asthma control, but not by atopy.
      C(alv) may possibly reflect alveolar inflammation in asthma.

PMID- 16627869
TI  - Quantitative proteomic analysis of post-translational modifications of human
      histones.
AB  - Histone proteins are subject to a range of post-transcriptional modifications in
      living cells. The combinatorial nature of these modifications constitutes the
      "histone code" that dictates chromatin structure and function during development,
      growth, differentiation, and homeostasis of cells. Deciphering of the histone
      code is hampered by the lack of analytical methods for monitoring the
      combinatorial complexity of reversible multisite modifications of histones,
      including acetylation and methylation. To address this problem, we used LC-MSMS
      technology and Virtual Expert Mass Spectrometrist software for qualitative and
      quantitative proteomic analysis of histones extracted from human small cell lung
      cancer cells. A total of 32 acetylations, methylations, and ubiquitinations were
      located in the human histones H2A, H2B, H3, and H4, including seven novel
      modifications. An LC-MSMS-based method was applied in a quantitative proteomic
      study of the dose-response effect of the histone deacetylase inhibitor (HDACi)
      PXD101 on histone acetylation in human cell cultures. Triplicate LC-MSMS runs at
      six different HDACi concentrations demonstrated that PXD101 affects acetylation
      of histones H2A, H2B, H3, and H4 in a site-specific and dose-dependent manner.
      This unbiased analysis revealed that a relative increase in acetylated peptide
      from the histone variants H2A, H2B, and H4 was accompanied by a relative decrease
      of dimethylated Lys(57) from histone H2B. The dose-response results obtained by
      quantitative proteomics of histones from HDACi-treated cells were consistent with
      Western blot analysis of histone acetylation, cytotoxicity, and dose-dependent
      expression profiles of p21 and cyclin A2. This demonstrates that mass
      spectrometry-based quantitative proteomic analysis of post-translational
      modifications is a viable approach for functional analysis of candidate drugs,
      such as HDAC inhibitors.

PMID- 16627870
TI  - Analysis of pooled DNA samples on high density arrays without prior knowledge of
      differential hybridization rates.
AB  - Array based DNA pooling techniques facilitate genome-wide scale genotyping of
      large samples. We describe a structured analysis method for pooled data using
      internal replication information in large scale genotyping sets. The method takes
      advantage of information from single nucleotide polymorphisms (SNPs) typed in
      parallel on a high density array to construct a test statistic with desirable
      statistical properties. We utilize a general linear model to appropriately
      account for the structured multiple measurements available with array data. The
      method does not require the use of additional arrays for the estimation of
      unequal hybridization rates and hence scales readily to accommodate arrays with
      several hundred thousand SNPs. Tests for differences between cases and controls
      can be conducted with very few arrays. We demonstrate the method on 384
      endometriosis cases and controls, typed using Affymetrix Genechip(c) HindIII 50 K
      arrays. For a subset of this data there were accurate measures of hybridization
      rates available. Assuming equal hybridization rates is shown to have a negligible
      effect upon the results. With a total of only six arrays, the method extracted
      one-third of the information (in terms of equivalent sample size) available with
      individual genotyping (requiring 768 arrays). With 20 arrays (10 for cases, 10
      for controls), over half of the information could be extracted from this sample.

PMID- 16627871
TI  - Impaired growth plate chondrogenesis in children with chronic illnesses.
AB  - In mammals, statural growth is primarily accomplished by endochondral
      ossification, which takes place at the growth plate. Growth plate chondrocyte
      proliferation, hypertrophy/differentiation, apoptosis, and cartilage matrix
      synthesis all contribute to chondrogenesis or cartilage formation, a process
      tightly coupled to the simultaneous remodeling of the cartilage into bone at the
      metaphyseal border of the growth plate. Growth plate chondrogenesis is regulated
      by the complex interaction of molecular signals acting systemically as well
      locally within the growth plate. This network is often dysregulated during
      chronic illnesses, thus resulting in impaired growth plate chondrogenesis and, in
      turn, growth failure. The principal events responsible for altered growth plate
      chondrogenesis in chronic illness are inflammation, protein/calorie deprivation,
      uremia/metabolic acidosis, glucocorticoids, and impaired GH/IGF-I axis.

PMID- 16627872
TI  - Reduced left ventricular function in hypoxemic newborn pigs: a strain Doppler
      echocardiographic study.
AB  - Myocardial dysfunction, hypotension, and increased pulmonary artery pressure are
      induced by asphyxia in neonates. We sought to define left ventricular (LV)
      systolic function by measuring longitudinal and radial contraction by strain
      Doppler echocardiography (SDE) in hypoxemic newborn pigs. Hypoxemia was induced
      in 11 anesthetized and instrumented newborn pigs by ventilation with 8% O2 in
      nitrogen. When mean arterial blood pressure (BP) decreased to 15 mm Hg or
      arterial base excess reached -20 mmol/L or less, the pigs were reoxygenated and
      ventilated for 150 min. Echocardiography was performed at baseline and during
      hypoxemia and reoxygenation. Baseline measurements of myocardial peak systolic
      strain demonstrated normal longitudinal shortening and radial thickening. During
      hypoxemia, systolic longitudinal shortening in the mid-posterior and septal
      segments changed to systolic stretching. Peak strain in the mid-lateral and
      anterior segments decreased but without signs of paradox wall motion. Short-axis
      peak strain remained positive during hypoxemia, although the amplitude was
      reduced and delayed with respect to timing. In the newborn pig heart, we found a
      complex and heterogeneous systolic pattern with distinct regional differences
      during global hypoxemia. Rapid changes in LV function during hypoxemia and
      reoxygenation are assessable by SDE, and the results indicate that longitudinal
      systolic contraction is more vulnerable to hypoxemic changes than radial
      contraction. To explore the full picture of a global hypoxemic injury, both long-
      and short-axis functions have to be considered.

PMID- 16627873
TI  - Platelet dysfunction in asphyxiated newborn piglets resuscitated with 21% and
      100% oxygen.
AB  - Hemostatic disturbances are common in asphyxiated newborns after resuscitation.
      We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or
      100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely
      instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia
      was induced with an inspired oxygen concentration of 10-15% for 2 h. Piglets were
      then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21%
      oxygen. Platelet counts and collagen (2, 5, and 10 microg/mL)-stimulated whole
      blood aggregation were studied before hypoxia and at 4 h of post
      hypoxia/reoxygenation. Platelet function was studied using transmission electron
      microscopy and by measuring plasma thromboxane B2 (TxB2) and matrix
      metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated
      without hypoxia/reoxygenation. The hypoxemic (PaO2 33 mm Hg) piglets developed
      hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets
      recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet
      aggregation ex vivo was impaired as evidenced by a rightward-downward shifting of
      the concentration-response curves. Electron microscopy showed features of
      platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased.
      Resuscitation with 100% but not 21% oxygen increased plasma TxB2 levels. Platelet
      counts decreased after hypoxia/reoxygenation but were not different between
      groups during the experiment. Resuscitation of hypoxic newborn piglets caused
      platelet activation with significant deterioration of platelet aggregation ex
      vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate
      the activation of prostaglandin-thromboxane mechanistic pathway.

PMID- 16627874
TI  - Pancreatic phospholipase A2 contributes to lung injury in experimental meconium
      aspiration.
AB  - To investigate the role of pancreatic (group I) secretory PLA2 (sPLA2-I) in the
      pathogenesis of meconium aspiration syndrome, human particulate meconium or its
      supernatant either before or after extraction of PLA2-I was insufflated into rat
      lungs. In addition, the pulmonary effects of intra-tracheal human and bovine PLA2
      I were studied. Lungs with saline instillation served as controls. Intrapulmonary
      particulate meconium (both before and after PLA2-I extraction), unlike meconium
      supernatant, resulted in markedly elevated lung tissue PLA2 catalytic activity
      and human PLA2-I concentrations when compared with controls. On the other hand,
      tissue concentrations of the group II PLA2 remained unchanged in all meconium
      lungs. Pulmonary PLA2-I concentrations further correlated positively with lung
      injury scores. Instillation of meconium-derived human PLA2-I, at a concentration
      of one-third of that in particulate meconium, did not raise PLA2 activity or
      concentrations of PLA2-I or PLA2-II in the lung tissue from the control level,
      but still resulted in significantly elevated lung wet/dry ratio and injury score.
      In contrast, insufflation of bovine pancreatic PLA2 increased the lung tissue
      enzyme activity and wet/dry ratio from the control level, but had no effect on
      the type II PLA2 concentration or lung injury score. Our data thus indicate that
      human pancreatic PLA2, introduced in high amounts within aspirated meconium
      especially in particulate form, is a potent inducer of lung tissue inflammatory
      injury.

PMID- 16627875
TI  - Deep inhalation prevents the respiratory elastance response to methacholine in
      rats.
AB  - The bronchodilator effect of deep inhalation (DI) may be assessed from the time
      course of respiratory system resistance (Rrs) and reactance (Xrs) measured by the
      forced oscillation technique at a single frequency. The aim of the study was to
      assess the effect of DI in the closed chest rat. Under anesthesia and mechanical
      ventilation, seven Brown Norway rats were given regular DI (BN-di) and six
      underwent continuous tidal ventilation (BN) throughout an otherwise similar
      methacholine (Mch) challenge protocol. Rrs and Xrs were monitored at 20 Hz and
      apparent respiratory system elastance (Ers) was computed from Xrs. After Mch
      nebulization, there was a significant increase in Rrs and Ers compared with
      saline. Ers, but not Rrs, decreased after the DI and BN-di were found to have
      lower Ers than BN. Thus, DI significantly alters Ers and its response to Mch.
      Computer simulations suggested reversal of increased viscoelasticity and/or
      inhomogeneous behavior by the DI in that model.

PMID- 16627876
TI  - Effects of transforming growth factor-beta and formula feeding on systemic immune
      responses to dietary beta-lactoglobulin in allergy-prone rats.
AB  - Early nutritional events have the potential to affect health outcomes in later
      life including the development of allergy. Food allergy is usually the first
      manifestation of allergy. Breast-feeding has been associated with a protective
      effect against the development of allergy, but the evidence is contradictory and
      the mechanisms involved are not clear. We hypothesize that milk cytokines, such
      as transforming growth factor beta (TGF-beta), play a role in regulating immune
      responses to dietary antigens. Using a rat pup model of gastrostomy feeding, the
      immune response profile, at weaning and post-weaning, of allergy-prone Brown
      Norway rats fed formula supplementation with TGF-beta was assessed. We show that
      feeding formula to allergy-prone rat pups results in increased total IgE
      immunoglobulin, beta-lactoglobulin (BLG) IgG1 antibody, and mucosal mast cell
      activation, as measured by serum rat mast cell protease II (RMCPII) levels in the
      gut. Supplementation of formula with physiological levels of TGF-beta down
      regulated the BLG IgG1 response as well as total IgE and mucosal mast cell
      activation. Supplementation of formula also resulted in an increase in Th1
      cytokines, interleukin (IL)-18, IL-12p40, IL-12p35, and interferon gamma (IFN
      gamma) and an increase in IL-10. In conclusion, TGF-beta supplementation of
      formula moved the immune response profile of allergy prone (Th2 type) rat pups
      toward a Th1 profile in the suckling period. Importantly, this immune profile
      persisted after weaning when TGF-beta was no longer present in the diet.

PMID- 16627877
TI  - Breast milk lactoferrin regulates gene expression by binding bacterial DNA CpG
      motifs but not genomic DNA promoters in model intestinal cells.
AB  - High-affinity binding of DNA by lactoferrin (LF) is an established phenomenon,
      but the biologic function of this interaction remains unclear. LF is an abundant
      breast milk protein (12.5-87.5 micromol/L) and is resistant to digestion in the
      infant gut. Regulation of gene expression by LF appears to be a major activity,
      particularly in modulating immune responses. We hypothesized that LF binding to
      DNA is a mechanism of gene regulation and aimed to identify the mechanism and
      physiologic sites of this activity. Our studies focused on two major biologic
      compartments of DNA: LF binding to proinflammatory bacterial DNA sequences (CpG
      motifs) in extracellular compartments and LF binding to genomic DNA promoters in
      the nucleus. LF 0.5 mmol/L inhibited CpG motif-induced nuclear factor-kappaB (NF
      kappaB) activation and interleukin (IL)-8 and IL-12 cytokine gene transcription
      in B cells. Intestinal epithelial cells were unresponsive to CpG motifs. However,
      significant LF transferred across M cell-like monolayers, specialized epithelial
      cells that transcytose intact macromolecules to underlying B-cell follicles in
      the intestine. LF did not activate gene expression by binding to putative
      response elements in epithelial and lymphoid cells. Nor did LF bind to putative
      response elements specifically in gel-shift assays. No nuclear localization of LF
      was detected in green fluorescent protein (GFP) tagging experiments. We conclude
      that breast milk LF regulates gene expression by binding CpG motifs
      extracellularly, with follicular B cells in the infant intestine a likely target.

PMID- 16627878
TI  - Liver hepcidin and stainable iron expression in biliary atresia.
AB  - Hepcidin is a proposed mammalian host defense peptide that was identified on the
      basis of its antimicrobial activity, but it was later shown to be a crucial
      regulator of iron homeostasis and a mediator of the anemia of chronic
      inflammation. Hepcidin and stainable iron expression in biliary atresia (BA) were
      investigated in this study. Fresh liver tissues were obtained from 10 patients in
      the early stage of BA when they underwent Kasai's procedure, 9 in the late stage
      of BA when they received liver transplantation and 5 controls receiving liver
      resection for benign lesions other than cholestasis or fibrosis. Real-time
      quantitative reverse-transcription PCR (QRT-PCR), immunohistochemical staining
      and ELISA were performed to gauge hepcidin mRNA and protein expression in liver
      and plasma. Archival liver specimens from patients in the early and late stages
      of BA were treated with Perls' acid ferrocyanide technique for hepatic stainable
      iron. The results demonstrated that liver hepcidin mRNA expression was 100-fold
      lower in late-stage BA than in the early stage by QRT-PCR. Significantly weaker
      liver hepcidin immunostaining and lower plasma hepcidin levels were found in late
      stage BA than in the early stage. There was also significantly lower stainable
      iron in the liver of late-stage BA. The major site of stainable iron was in
      Kupffer cells. The results support a role for hepcidin as a key regulator of
      mammalian iron metabolism and chronic inflammation, whose expression correlates
      with the degree of stainable iron in BA.

PMID- 16627879
TI  - Systemic effects of orally-administered zinc and tin (IV) metalloporphyrins on
      heme oxygenase expression in mice.
AB  - Some metalloporphyrins (Mps) inhibit heme oxygenase (HO), the rate-limiting
      enzyme in the production of bilirubin, and are potential compounds for the
      treatment of neonatal jaundice. We studied the safety and efficacy of Mps
      following oral administration. Adult HO-1-luc reporter mice were administered 30
      micromol/kg body weight of tin mesoporphyrin (SnMP), zinc bis glycol
      deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP), or vehicle by oral
      gavage. Bilirubin production was measured as total body carbon monoxide (CO)
      excretion (VeCO). HO activity was quantitated via CO measurements by gas
      chromatography. HO-1 protein was determined by Western blot. HO-1 transcription
      levels were assessed by in vivo bioluminescence imaging. A significant 28%
      decrease in bilirubin production occurred within 3 h of SnMP treatment and
      persisted beyond 48 h. Bilirubin production decreased 15% and 9% by 3 h after
      administration of ZnBG and ZnPP, respectively, but returned to baseline within 48
      h. Maximal inhibition of liver, spleen, and intestine HO activity was seen at 3 h
      with inhibitory effects decreasing in the order: SnMP > or = ZnBG > or = ZnPP.
      After SnMP treatment, HO-1 transcription increased 5.7-fold after 24 h.
      Furthermore, liver and spleen HO-1 protein significantly increased 3.7- and 2.0
      fold, respectively, after 24 h. HO-1 transcription and protein were not affected
      in ZnBG- or ZnPP-treated mice. We conclude that the three Mps are absorbed at
      different rates in the mouse and affect bilirubin production and HO-1 expression
      in a tissue- and time-dependent manner.

PMID- 16627880
TI  - Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in
      developing infants.
AB  - Astrocyte end-feet ensheathe blood vessels in the brain and are believed to
      provide structural integrity to the cerebral vasculature. We sought to determine
      in developing infants whether the coverage of blood vessels by astrocyte end-feet
      is decreased in germinal matrix (GM) compared with cerebral cortex and white
      matter (WM), which may cause fragility of the GM vasculature. Therefore, we
      evaluated the perivascular coverage by astrocyte end-feet in these areas. We
      double-labeled the brain sections with astroglial markers [glial fibrillary
      acidic protein (GFAP), aquaporin-4 (AQP4), and S-100beta] and a vascular marker,
      laminin. Perivascular coverage by GFAP+ astrocyte end-feet increased consistently
      as a function of gestational age (GA) in cortex and WM from 19 to 40 wk. Compared
      with GFAP, AQP4+ astrocyte end-feet developed at an earlier GA, ensheathing about
      63% of blood vessels for 23-40 wk in cortex, WM, and GM. Coverage by GFAP+
      perivascular end-feet was decreased in GM compared with cortex and WM from 23 to
      34 wk. There was no difference in the coverage by AQP4+ end-feet among the three
      areas in these infants. The expression of AQP4, a water channel molecule, in the
      astrocyte end-feet was not significantly different between premature and mature
      infants, suggesting similar risk of brain edema in preterm and term infants in
      pathologic conditions. More importantly, the lesser degree of GFAP expression in
      astrocyte end-feet of GM compared with cortex and WM may reflect a cytoskeletal
      structural difference that contributes to the fragility of GM vasculature and
      propensity to hemorrhage.

PMID- 16627881
TI  - Acute hypoxia-ischemia results in hydrogen peroxide accumulation in neonatal but
      not adult mouse brain.
AB  - The neonatal brain responds differently to hypoxic-ischemic injury and may be
      more vulnerable than the mature brain due to a greater susceptibility to
      oxidative stress. As a measure of oxidative stress, the immature brain should
      accumulate more hydrogen peroxide (H2O2) than the mature brain after a similar
      hypoxic-ischemic insult. To test this hypothesis, H2O2 accumulation was measured
      in postnatal day 7 (P7, neonatal) and P42 (adult) CD1 mouse brain regionally
      after inducing HI by carotid ligation followed by systemic hypoxia. H2O2
      accumulation was quantified at 2, 12, 24, and 120 h after HI using the
      aminotriazole (AT)-mediated inhibition of catalase spectrophotometric method.
      Histologic injury was determined by an established scoring system, and infarction
      volume was determined. P7 and P42 animals were subjected to different durations
      of hypoxia to create a similar degree of brain injury. Despite similar injury,
      significantly less H2O2 accumulated in P42 mouse cortex compared with P7 at 2,
      12, and 24 h after HI. In addition, less H2O2 accumulated in P42 mouse
      hippocampus compared with P7 hippocampus at 2 h. Since immature neurons are more
      vulnerable to the toxic effects of H2O2 than mature neurons, this increased
      accumulation in the immature brain may explain why the neonatal brain may be more
      devastated, even after a milder degree of acute hypoxic-ischemic injury.

PMID- 16627882
TI  - Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic
      ischemic brain injury in neonatal rats.
AB  - Hypoxic ischemic (HI) injury in neonates may have devastating, long-term
      consequences. Recently completed clinical trials in HI neonates indicate that
      hypothermia within 6 h of birth results in modest improvement in the combined
      outcome of death or severe disability. The aim of this study was to investigate
      the effects of combining hypothermia and N-acetylcysteine (NAC) on brain injury,
      neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were
      subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2
      h. Systemic hypothermia (30 + 0.5 degrees C) was induced immediately after the
      period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by
      intraperitoneal injection daily until sacrifice. Brain infarct volumes were
      significantly reduced at 48 h post-HI in the hypothermia plus NAC group (21.5 +/-
      3.84 mm3) compared with vehicle (240.85 +/- 4.08 mm3). Neonatal reflexes were
      also significantly improved by combination therapy at days 1 and 7. There was a
      significant loss of right hemispheric brain volume in the untreated group at 2
      and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC
      group and were not significantly different when compared with the sham group.
      Similarly, increased myelin expression was seen in brain sections from
      hypothermia plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic
      Protein (MBP) and Proteolipid protein (PLP). These results indicate that
      hypothermia plus NAC combination therapy improves infarct volume, myelin
      expression and functional outcomes after focal HI injury.

PMID- 16627883
TI  - Intravenous infusion of an antisense oligonucleotide results in exon skipping in
      muscle dystrophin mRNA of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease that is
      characterized by muscle dystrophin deficiency. We report that intravenous (IV)
      infusion of an antisense oligonucleotide created an in-frame dystrophin mRNA from
      an out-of-frame DMD mutation (via exon skipping) which led to muscle dystrophin
      expression. A 10-year-old DMD patient possessing an out-of-frame, exon 20
      deletion of the dystrophin gene received a 0.5 mg/kg IV infusion of an antisense
      31-mer phosphorothioate oligonucleotide against the splicing enhancer sequence of
      exon 19. This antisense construct was administered at one-week intervals for 4
      wk. No side effects attributable to infusion were observed. Exon 19 skipping
      appeared in a portion of the dystrophin mRNA in peripheral lymphocytes after the
      infusion. In a muscle biopsy one week after the final infusion, the novel in
      frame mRNA lacking both exons 19 and 20 was identified and found to represent
      approximately 6% of the total reverse transcription PCR product. Dystrophin was
      identified histochemically in the sarcolemma of muscle cells after
      oligonucleotide treatment. These findings demonstrate that phosphorothioate
      oligonucleotides may be administered safely to children with DMD, and that a
      simple IV infusion is an effective delivery mechanism for oligonucleotides that
      lead to exon skipping in DMD skeletal muscles.

PMID- 16627884
TI  - Sonographic maturation of third-trimester cerebellar foliation after birth.
AB  - The development of cerebellar folia of third-trimester preterms has not been
      described with ultrasound before. We set out to determine normal development of
      the pons and cerebellar folia for future measurements of hypoplasia and atrophy.
      Study sonograms were made in preterms admitted to the neonatal intensive care
      unit with postmenstrual age (PMA) from 25 wk until term. On a weekly basis,
      transcranial measurements were made in the axial and coronal planes at the
      asterion with high-frequency transducers (8.5 and 13 MHz). The axial images
      showed the pons and fourth ventricle. The coronal images showed cerebellar folia
      and white matter. In the same coronal plane, the depth of cerebellar fissures at
      the rostral cerebellar convexity could be observed. A total of 172 cranial
      sonograms were performed on 98 neonates. The development of folia could be
      measured with ultrasound through the asterion. We showed that pons area, mean of
      three fissure depths, hemisphere area, and number of folia in the horizontal
      fissure correlated significantly with PMA. Hemisphere area described the same
      trend of growth as the transverse cerebellar diameter used in fetal sonography.

PMID- 16627885
TI  - Variability of the initial phase of the ventilatory response to hypoxia in
      sleeping infants.
AB  - Most of the available data on the hypoxic ventilatory response (HVR) in infants
      has been obtained in quiet sleep (QS), and only one study has made repeated tests
      in the same infant. We aimed to gain a more complete knowledge of the maturation
      and consistency of the initial phase of the HVR by performing multiple tests in
      both QS and active sleep (AS) over the first 6 mo of life in term infants.
      Fifteen healthy term infants were studied with daytime polysomnography
      longitudinally at 2-5 wk, 2-3 mo, and 5-6 mo after birth. Each infant received
      multiple hypoxic (15% O2, balance N2) challenges (three or more) in both AS and
      QS. In AS, infants consistently aroused to hypoxia; however, in QS, infants both
      aroused and failed to arouse. The initial phase of the HVR varied considerably
      between infants with the changes in ventilation/kg [SD of inspired minute
      ventilation per kilogram of body weight (V(I)/kg)] being more variable during AS
      than QS at all three ages and overall decreasing with postnatal age in both sleep
      states. The variability between replicate V(I)/kg measurements was also
      significantly greater in AS compared with QS at 2-5 wk postnatal age. There was
      no evidence of habituation to repeated hypoxic tests in either sleep state. Our
      study has demonstrated that the initial phase of the HVR is variable both between
      and within term infants in both AS and QS, with responses being markedly more
      variable during AS, and becoming more consistent with increasing postnatal age.
      By performing only one test or by failing to account for arousal responses,
      previous studies may not have detected the natural variation of the infant HVR.

PMID- 16627886
TI  - Diaphragm electrical activity during expiration in mechanically ventilated
      infants.
AB  - The presence of diaphragm electrical activity (EAdi) during expiration is
      believed to be involved in the maintenance of end-expiratory lung volume (EELV)
      and has never been studied in intubated and mechanically ventilated infants. The
      aim of this study was to quantify the amplitude of diaphragm electrical activity
      present during expiration in mechanically ventilated infants and to measure the
      impact of removing positive end-expiratory pressure (PEEP) on this activity. We
      studied the EAdi in 16 ready-to-be weaned intubated infants who were breathing on
      their prescribed ventilator and PEEP settings. In all 16 patients, 5 min of data
      were collected on the prescribed ventilator settings. In a subset of eight
      patients, the PEEP was briefly reduced to zero PEEP (ZEEP). EAdi was recorded
      with miniaturized sensors placed on a conventional nasogastric feeding tube.
      Airway pressure (Paw) was also measured. For each spontaneous breath, we
      identified the neural inspiration and neural expiration. Neural expiration was
      divided into quartiles (Q1, Q2, Q3, and Q4), and the amplitude of EAdi calculated
      for each Q1-Q4 represented 95 +/- 29%, 31 +/- 15%, 15 +/- 8%, and 12 +/- 7%,
      respectively, of the inspiratory EAdi amplitude. EAdi for Q3-Q4 significantly
      increased during ZEEP, and decreased after reapplication of PEEP. These findings
      confirm that the diaphragm remains partially active during expiration in
      intubated and mechanically ventilated infants and that removal of PEEP affects
      this tonic activity. This could have potential implications on the management of
      PEEP in intubated infants.

PMID- 16627887
TI  - Changes in behavior and attentional capacity after adenotonsillectomy.
AB  - The objective of this study was to quantify behavioral and attention capacity
      changes in children aged 4-11 y before and 3 mo after adenotonsillectomy (A/T).
      Overnight cardiorespiratory recordings were performed in 61 "behaviorally normal"
      children 1 wk before A/T. Tests of sustained attention using visual and auditory
      continuous performance tests (CPT) were completed by children 1 wk before and 3
      mo after A/T. Behavioral Assessment Scales for Children (BASC) and a sleep
      questionnaire were completed by the parent/s at these same times. Results from
      overnight cardiorespiratory recordings showed that the children had mild sleep
      related breathing disorders (SRBD) preoperatively with a mean apnea/hypopnea
      index of 3.0/h and a movement awakening index of 2.5/h. The majority had parent
      perceived sleep and breathing difficulties that significantly improved post-A/T.
      BASC T scores for externalizing and internalizing behaviors improved post-A/T,
      e.g., behavioral symptom index mean pre-A/T was 56.2 (95% confidence interval,
      52.8-59.6) compared with 50.9 (48.5-53.5) post-A/T. Some measures indicative of
      impulsivity and attentiveness obtained from the visual CPT before surgery,
      improved post-A/T, but no change was observed in any auditory CPT measures. Our
      data confirm improvements in subjective measures of sleep problems in children
      treated for SRBD and strengthen the notion of treating the disorder, not only
      related to the obvious clinical condition but also to the underlying sleep
      problems and adverse effects on daytime behavior and attention.

PMID- 16627888
TI  - Relationship between umbilical cord essential fatty acid content and the quality
      of general movements of healthy term infants at 3 months.
AB  - Prenatal essential fatty acid (EFA) status might be an important factor in the
      development of the central nervous system (CNS). The aim of the present study was
      to evaluate the relationship between the fatty acid compositions of the umbilical
      blood vessels at birth, used as a proxy of prenatal EFA status, and quality of
      general movements (GMs) at 3 mo. Umbilical artery and vein fatty acid
      compositions were investigated in a mixed group of breastfed infants and infants
      fed with formula with or without long-chain polyunsaturated fatty acid (LCPUFA)
      supplementation. At the age of 3 mo, video assessment of the quality of GMs was
      performed to evaluate neurologic condition. The quality of GMs was scored by
      assessing the degree of variation, complexity, and fluency. Outcomes were
      classified as normal-optimal, normal suboptimal, mildly abnormal, and definitely
      abnormal movements. Information on potential confounders, including the type of
      postnatal feeding, was collected prospectively. Associations between fatty acid
      status at birth and quality of GMs were investigated, and multinomial logistic
      regression analyses were carried out. None of the infants showed definitely
      abnormal movements. Infants with mildly abnormal GMs had a lower EFA index, lower
      arachidonic acid (AA) content, higher total n-9 fatty acid, and higher total
      monounsaturated fatty acid (MUFA) content in the umbilical artery compared with
      infants with normal GMs. Multivariate analyses confirmed these findings. We
      conclude that mildly abnormal GMs are associated with a less favorable EFA status
      in the umbilical artery.

PMID- 16627889
TI  - Breast milk fatty acids may link innate and adaptive immune regulation: analysis
      of soluble CD14, prostaglandin E2, and fatty acids.
AB  - In addition to its role in sensing intraluminal microbial antigens, soluble
      (s)CD14 may regulate immune responses by its lesser known function as a lipid
      carrier with possible influences in the production of fatty acid-derived
      eicosanoids. We investigated the interrelations of fatty acids, prostaglandin E2
      (PGE2), and sCD14 and their role in infant atopic eczema during the first year of
      life. Serum and breast milk samples from mothers and serum samples from their
      infants were collected at infant's age 3 mo and analyzed for sCD14 and PGE2
      concentrations and for fatty acid compositions. The main correlation of sCD14 was
      with arachidonic acid (20:4n-6) (AA). Dihomo-gamma-linolenic acid (20:3n-6)
      (DHGLA) and the ratio of n-6 to n-3 fatty acids correlated positively and
      docosahexaenoic acid (22:6n-3) (DHA) and sum of n-3 fatty acid negatively with
      PGE2 in mother's serum and linoleic acid (LA) negatively with PGE2 in breast
      milk. Soluble CD14 tended to be higher and LA, total polyunsaturated fatty acid
      (PUFA), and sum of n-6 fatty acids were lower in breast milk received by infants
      with atopic eczema compared with those without. These results suggest that fatty
      acids contribute to the regulation of innate and adaptive immune responses and
      link intraluminal exposures, mother's diet, and microbes.

PMID- 16627890
TI  - Changes in sucking performance from nonnutritive sucking to nutritive sucking
      during breast- and bottle-feeding.
AB  - Our aim was to obtain a better understanding of the differences between breast
      feeding and bottle-feeding, particularly with regard to how sucking performance
      changes from nonnutritive sucking (NNS) to nutritive sucking (NS). Twenty-two
      normal term infants were studied while breast-feeding at 4 and 5 d postpartum.
      Five of the 22 infants were exclusively breast-fed, but we tested the other 17
      infants while breast-feeding and while bottle-feeding. Before the milk ejection
      reflex (MER) occurs, little milk is available. As such, infants perform NNS
      before MER. For bottle-feeding, a one-way valve was affixed between the teat and
      the bottle so that the infants needed to perform NNS until milk flowed into the
      teat chamber. At the breast, the sucking pressure (-93.1 +/- 28.3 mm Hg) was
      higher during NNS compared with NS (-77.3 +/- 27.0 mm Hg). With a bottle, the
      sucking pressure was lower during NNS (-27.5 +/- 11.2 mm Hg) compared with NS (
      87.5 +/- 28.5 mm Hg). Sucking frequency was higher and sucking duration was
      shorter during NNS compared with that during NS both at the breast and with a
      bottle. There were significant differences in the changes of sucking pressure and
      duration from NNS to NS between breast- and bottle-feeding. The change in sucking
      pressure and duration from NNS to NS differed between breast-feeding and bottle
      feeding. Even with a modified bottle and teats, bottle-feeding differs from
      breast-feeding.

PMID- 16627891
TI  - Effects of early amino acid administration on leucine and glucose kinetics in
      premature infants.
AB  - We previously showed that, in prematurely born infants, an anabolic state without
      metabolic acidosis can be achieved upon intravenous amino acid (AA)
      administration in the immediate postnatal phase, despite a low energy intake. We
      hypothesized that the anabolic state resulted from an increased protein synthesis
      and not a decreased proteolysis. Furthermore, we hypothesized that the energy
      needed for the higher protein synthesis rate would be derived from an increased
      glucose oxidation. To test our hypotheses, 32 ventilated premature infants (<1500
      g) received intravenously either solely glucose or glucose and 2.4 g AA/kg/d
      immediately postnatally. On postnatal d 2, each group received primed continuous
      infusions of either [1-13C]leucine or [U-13C6]glucose. 13CO2 enrichments in
      expiratory air and plasma [1-13C]alpha-KICA (as an intracellular leucine
      precursor) and [U-13C6]glucose enrichments were measured by mass spectrometry
      techniques. The AA administration resulted in an increased incorporation of
      leucine into body protein and a higher leucine oxidation rate, whereas leucine
      release from proteolysis was not affected. Glucose oxidation rate did not
      increase upon AA administration. In conclusion, the anabolic state resulting from
      AA administration in the immediate postnatal period resulted from increased
      protein synthesis and not decreased proteolysis. The energy needed for the
      additional protein synthesis was not derived from an increased glucose oxidation.

PMID- 16627892
TI  - A noninvasive, sensitive, specific, and reliable approach to assess whole-body
      nitric oxide synthesis in children.
AB  - Determination of nitric oxide (NO) synthesis in vivo is essential to understand
      the pathophysiologic role and therapeutic implications of the L-arginine/NO
      pathway in pediatric diseases. The aim of this study was to establish a
      noninvasive, sensitive, specific, and reliable approach to determine whole-body
      NO synthesis in healthy children. Seventeen healthy children (eight boys/nine
      girls, 4-16 y) were studied twice, and six of them on three occasions. Fasting
      children received a single oral dose of nonradioactive L-[15N]2-guanidino
      arginine (5 mg/kg body weight). Complete 24-h urine collections were subsequently
      performed on an ambulatory basis. Total urinary nitrate excretion and
      [15N]nitrate enrichments were determined using high-pressure liquid
      chromatography and gas chromatography-isotope ratio mass spectrometric
      techniques. The mean urinary [15N]nitrate enrichments on the 0-12-h/12-24-h
      collection periods of three study visits were 0.9309%/0.5910%, 0.9056%/0.6214%,
      and 0.9087%/0.6059%. The levels of 24-h urinary [15N]nitrate excretion [mean (95%
      confidence interval)] for three study visits were 11.70 (8.85-14.54), 12.21 (9.61
      14.82), and 11.37 (7.96-14.77) microg [15N]nitrogen-nitrate/mmol creatinine,
      respectively. Within-subject coefficient of variation for 24-h urinary
      [15N]nitrate excretion was 11.87%. Agreement among results was assessed by
      intraclass correlation coefficient (0.93) and coefficient of repeatability
      (4.08). The percentage of L-[15N]2-guanidino arginine dose directed to nitric
      oxide synthesis was 0.221% [0.181-0.261]. Multiple regression analysis showed age
      as the predictor variable of whole-body NO synthesis. These results show for the
      first time that a single oral administration of L-[15N]2-guanidino arginine can
      be used to reliably and specifically determine whole-body NO synthesis in
      children.

PMID- 16627893
TI  - American Pediatric Society Presidential Address 2005: Pediatric scientists
      priming the pipeline.

PMID- 16627894
TI  - Thematic review series: lipid posttranslational modifications. Lysosomal
      metabolism of lipid-modified proteins.
AB  - Much is now understood concerning the synthesis of prenylated and palmitoylated
      proteins, but what is known of their metabolic fate? This review details
      metabolic pathways for the lysosomal degradation of S-fatty acylated and
      prenylated proteins. Central to these pathways are two lysosomal enzymes,
      palmitoyl-protein thioesterase (PPT1) and prenylcysteine lyase (PCL). PPT1 is a
      soluble lipase that cleaves fatty acids from cysteine residues in proteins during
      lysosomal protein degradation. Notably, deficiency in the enzyme causes a
      neurodegenerative lysosomal storage disorder, infantile neuronal ceroid
      lipofuscinosis. PCL is a membrane-associated flavin-containing lysosomal
      monooxygenase that metabolizes prenylcysteine to prenyl aldehyde through a
      completely novel mechanism. The eventual metabolic fates of other lipidated
      proteins (such as glycosylphosphatidylinositol-anchored and N-myristoylated
      proteins) are poorly understood, suggesting directions for future research.

PMID- 16627895
TI  - Continuous electroencephalography for subarachnoid hemorrhage has come of age.

PMID- 16627896
TI  - CSF spectrophotometry in questionable SAH: a continental divide.

PMID- 16627897
TI  - Prognostic significance of continuous EEG monitoring in patients with poor-grade
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Predicting outcome in patients with poor-grade subarachnoid
      hemorrhage (SAH) may help guide therapy and assist in family discussions. The
      objective of this study was to determine if continuous electroencephalogram
      (cEEG) monitoring results are predictive of 3-month outcome in critically ill
      patients with SAH. METHODS: We prospectively studied 756 patients with SAH over a
      7-year period. Functional outcome was assessed at 3 months with the modified
      Rankin Scale (mRS). Patients that underwent cEEG monitoring were retrospectively
      identified and EEG findings were collected. Multivariate logistic regression
      analysis was performed to identify EEG findings associated with poor outcome,
      defined as mRS 4 to 6 (dead or moderately to severely disabled). RESULTS: In 116
      patients with SAH, cEEG monitoring and 3-month mRS were available. Of these
      patients, 88% had a Hunt & Hess grade of 3 or worse on admission. After
      controlling for age, Hunt & Hess grade, and presence of intraventricular
      hemorrhage on admission CT scan, poor outcome was associated with the absence of
      sleep architecture (80 versus 47%; odds ratio [OR] 4.3, 95%-confidence interval
      [CI] 1.1-17.2) and the presence of periodic lateralized epileptiform discharges
      (PLEDS) (91 versus 66% OR 18.8, 95%-CI 1.6-214.6). In addition, outcome was poor
      in all patients with absent EEG reactivity (n = 8), generalized periodic
      epileptiform discharges (n = 12), or bilateral independent PLEDs (n = 5), and in
      92% (11 of 12) of patients with nonconvulsive status epilepticus. CONCLUSIONS:
      cEEG monitoring provides independent prognostic information in patients with poor
      grade SAH, even after controlling for clinical and radiological findings.
      Unfavorable findings include periodic epileptiform discharges, electrographic
      status epilepticus, and the absence of sleep architecture.

PMID- 16627898
TI  - Intra-arterial papaverine used to treat cerebral vasospasm reduces brain oxygen.
AB  - INTRODUCTION: Intra-arterial papaverine (IAP) is used to treat symptomatic
      cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). IAP,
      however, can increase intracranial pressure (ICP). In this study we examined
      whether IAP alters brain oxygen (BtO2). METHODS: Poor clinical grade (Hunt & Hess
      IV or V) SAH patients who underwent continuous ICP and BtO2 monitoring during IAP
      infusion for symptomatic cerebral vasospasm were evaluated as part of a
      prospective observational study. RESULTS: Data are available for five patients
      (median age 58) who received IAP for cerebral vasospasm 4 to 7 days after SAH. In
      each patient, angiographic vasospasm was improved on postinfusion angiogram. Mean
      ICP before IAP was 23.04 +/- 1.18 mmHg; it increased immediately after IAP
      infusion and remained elevated (29.89 +/- 1.18 mmHg; p < 0.05) during IAP and for
      approximately 10 minutes after IAP ended. Baseline mean arterial pressure (MAP)
      was 110.55 +/- 1.36 mmHg. During IAP treatment MAP remained stable (110.90 +/-
      2.00 mmHg; p = 0.31). Mean BtO2 before IAP was 32.99 +/- 1.45 mmHg. There was a
      significant BtO2 decrease in all patients during IAP to a mean of 22.96 +/- 2.9
      mmHg (p < 0.05). BtO2 returned to baseline within 10 minutes after IAP ended.
      There was a modest relationship between the ICP increase and BtO2 decrease (R2 =
      0.526). CONCLUSION: IAP infusion to treat cerebral vasospasm following SAH can
      increase ICP and reduce BtO2. The IAP-induced reduction in BtO2 may help explain
      why IAP, although it reverses arterial narrowing, does not improve patient
      outcome.

PMID- 16627899
TI  - MR imaging and prognosis of hypoxic-ischemic leukoencephalopathy.
AB  - OBJECTIVE: To correlate prognosis of hypoxic-ischemic white-matter injury with
      magnetic resonance imaging (MRI). METHODS: In a retrospective review at an urban
      medical center, three adult and three pediatric patients with predominant white
      matter involvement caused by hypoxic- ischemic injury were evaluated over a 15
      month period. RESULTS: Five patients with MRI-defined hypoxic-ischemic
      leukoencephalopathy had a favorable outcome, and one with associated diffusion
      weighted abnormality of deep gray structures died. CONCLUSION: The prognosis of
      hypoxic-ischemic leukoencephalopathy is more favorable than previously reported,
      and diffusion-weighted imaging abnormality of deep gray structures was associated
      with a poor outcome.

PMID- 16627900
TI  - Analysis of dynamic autoregulation assessed by the cuff deflation method.
AB  - INTRODUCTION: Dynamic testing of cerebral pressure autoregulation is more
      practical than static testing for critically ill patients. The process of cuff
      deflation is innocuous in the normal subject, but the systemic and cerebral
      effects of cuff deflation in severely head-injured patients have not been
      studied. The purposes of this study were to examine the physiological effects of
      cuff deflation and to study their impact on the calculation of autoregulatory
      index (ARI). METHOD: In 24 severely head-injured patients, 388 thigh cuff
      deflations were analyzed. The physiological parameters were recorded before,
      during, and after a transient decrease in blood pressure. Autoregulation was
      graded by generating an ARI value from 0 to 9. RESULTS: Mean arterial blood
      pressure (MAP) dropped rapidly during the first 2-3 seconds, but the nadir MAP
      was not reached until 8 +/- 7 seconds after the cuff deflation. MAP decreased by
      an average value of 19 +/- 5 mmHg. Initially the tracings for MAP and cerebral
      perfusion pressure (CPP) were nearly identical, but after 30 seconds, variable
      increases in intracranial pressure caused some differences between the MAP and
      CPP curves. The difference between the ARI values calculated twice using MAP as
      well as CPP was zero for 70% of left-sided studies and 73% for right-sided
      studies and less than or equal to 1 for 93% of left- and 95% of right-sided cuff
      deflations. CONCLUSION: Transient and relatively minor perturbations were
      detected in systemic physiology induced by dynamic testing of cerebral pressure
      autoregulation. Furthermore, this study confirms that the early changes in MAP
      and CPP after cuff deflation are nearly identical. MAP can substitute for CPP in
      the calculation of ARI even in the severely brain-injured patient.

PMID- 16627901
TI  - Posterior reversible encephalopathy syndrome caused by hypertensive
      encephalopathy and acute uremia.
AB  - INTRODUCTION: The posterior reversible encephalopathy syndrome (PRES) is a
      recently proposed cliniconeuroradiological entity. The most common causes of PRES
      are hypertensive encephalopathy, eclampsia, cyclosporin A neurotoxicity, and the
      uremic encephalopathy. On magnetic resonance imaging (MRI) studies, edema has
      been reported in a relatively symmetrical pattern, typically in the subcortical
      white matter and occasionally in the cortex of the posterior circulation area of
      the cerebrum. METHODS AND RESULTS: A 19-year-old woman undergoing chronic
      hemodialysis was admitted with encephalopathy. High signal intensity was seen
      bilaterally in the subcortical and deep white matter areas of the temporal,
      frontal, parietal, and occipital lobes on cranial MRI. CONCLUSION: Particular
      attention needs to be given to PRES because initiation of appropriate
      intervention can reverse the encephalopathic condition in most cases. Cerebral
      lesions may be more prominent in the anterior circulation area in some patients.

PMID- 16627902
TI  - Paraneoplastic coma and acquired central alveolar hypoventilation as a
      manifestation of brainstem encephalitis in a patient with ANNA-1 antibody and
      small-cell lung cancer.
AB  - INTRODUCTION: Paraneoplastic neurological disorders are a well recognized
      complication of malignancy. METHODS: A case report to expand the currently
      described clinical manifestations of type 1 antineuronal antibody (ANNA-1)
      associated paraneoplastic encephalomyelitis to include coma. RESULTS: We present
      an unusual case of fluctuating coma and rapid fulminant progression to acute
      respiratory failure from central alveolar hypoventilation caused by ANNA-1
      paraneoplastic encephalomyelitis associated with small-cell lung carcinoma.
      Paraneoplastic infiltration of the brainstem and cerebellum, including
      respiratory and arousal centers, was documented on autopsy. CONCLUSIONS:
      Paraneoplastic encephalomyelitis should be considered as a possible cause of coma
      and central alveolar hypoventilation.

PMID- 16627903
TI  - Prolonged coma from refractory status epilepticus.
AB  - OBJECTIVE: Status epilepticus is a life-threatening medical condition. In its
      most severe form, refractory status epilepticus (RSE) seizures may not respond to
      first and second-line anti-epileptic drugs. RSE is associated with a high
      mortality and significant medical complications in survivors with prolonged
      hospitalizations. METHODS: We describe the clinical course of RSE in the setting
      of new onset lupus in a 31-year-old male who required prolonged barbiturate coma.
      RESULTS: Seizure stopped on day 64 of treatment. Prior to the resolution of
      seizures, discussion around withdrawal of care took place between the physicians
      and patient's family. Medical care was continued because of the patient's age,
      normal serial MRI studies, and the patient's reversible medical condition.
      CONCLUSION: Few evidence-based data exist to guide management of RSE. Our case
      emphasizes the need for continuous aggressive therapy when neuroimaging remains
      normal.

PMID- 16627904
TI  - Reversibility of extensive hemispheric cytotoxic cerebral edema following
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Cerebral edema, as assessed by computer-assisted tomography, has
      been proposed as a prognosis factor of poor outcome following aneurysmal
      subarachnoid hemorrhage. However, this radiological finding might wrongly
      influence the decision to maintain or withdraw treatment in critically ill
      patients. CASE REPORT: We present the case of a 63-year-old female presenting
      with poor clinical grade after an aneurysmal rupture that developed extensive
      right hemispheric cytotoxic edema. With appropriate treatment, the brain edema
      progressively resolved and the clinical state improved. CONCLUSION: We discuss
      the importance of recognizing the possible reversibility of such extensive
      hemispheric edema and its relevance to patient management.

PMID- 16627905
TI  - Postoperative confusion and basilar artery stroke.
AB  - INTRODUCTION: Non-focal postoperative mental status changes can be challenging.
      METHODS: Single patient case report and medical literature review. RESULTS: We
      describe a 67-year-old male who was admitted for radical cystectomy and ileal
      conduit urinary diversion. General anesthesia was uneventful and the patient
      remained hemodynamically stable throughout the procedure. At the end of the
      procedure, the patient's trachea was extubated. Initially, he was arousable, able
      to move all extremities, and answer questions appropriately. Over the next 2
      hours, his mental status waxed and waned and respirations became irregular. An
      emergent head computed tomogram without contrast revealed a hyperdense basilar
      artery consistent with acute thrombosis. Vascular radiology intervention occurred
      approximately 9 hours after the onset of symptoms, but there was no improvement
      in the patient's neurological status and he subsequently died. CONCLUSION:
      Although nonfocal postoperative mental status changes are common and often
      secondary to benign etiologies, they may herald more significant pathology,
      including stroke. Patients with postoperative mental status changes should be
      evaluated carefully to identify life-threatening and treatable etiologies. Recent
      advances in the acute care of stroke, such as thrombolysis and angioplasty, can
      improve outcome if instituted promptly.

PMID- 16627906
TI  - Raccoon eyes following vigorous sneezing.

PMID- 16627907
TI  - Spectrophotometry for cerebrospinal fluid pigment analysis.
AB  - The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is
      reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are
      introduced and discussed with regard to clinical differential diagnosis and
      potentially confounding variables (the four T's: traumatic tap, timing, total
      protein, and total bilirubin). The practical laboratory aspects of
      spectrophotometry and automated techniques are presented in the context of
      analytical and clinical specificity and sensitivity. The perceptual limitations
      of human color vision are highlighted and the use of visual assessment of the CSF
      is discouraged in light of recent evidence from a national audit in the United
      Kingdom. Finally, future perspectives including the need for longitudinal CSF
      profiling and routine spectrophotometric calibration are outlined.

PMID- 16627908
TI  - Laryngospasm in neurological diseases.
AB  - Laryngospasm is a clinical symptom characterized by involuntary spasms of the
      laryngeal muscles, which leads to paroxysms of coughing, inspiratory stridor, and
      sometimes to episodes of complete upper-airway occlusion. Although laryngospasm
      is a symptom mainly seen in otolaryngeal diseases and in the context of
      anesthesiological complications, it also occurs in neurological disorders. In
      this review of the occurrence of laryngospasms in neurological diseases, the
      clinical symptomatology, additional circumstances, possible underlying causes,
      and therapeutic options are presented.

PMID- 16627909
TI  - Neuroprotection for ischemic stroke using hypothermia.
AB  - The development of animal models of acute stroke has allowed the evaluation of
      mild and moderate hypothermia as a therapeutic modality in this clinical setting.
      Studies have demonstrated that animals subjected to hypothermia up to 3 hours
      after the primary central nervous system insult have reduced mortality and
      neuronal injury, and improved neurological outcome. These results warranted the
      evaluation of hypothermia in clinical trials. Even though hypothermia has potent
      neuroprotective effects in animal models of ischemic stroke, there are only a few
      clinical studies of therapeutic hypothermia in humans. Because of the small
      number of patients in the studies and the absence of matched controls, clinical
      studies are considered pilot studies for feasibility and safety. Thus,
      therapeutic hypothermia for ischemic stroke remains a promising but fiercely
      debated therapeutic modality. This review summarizes the animal model studies
      that have led to clinical trials in acute ischemic stroke. The existing
      techniques for inducing brain cooling, the mechanisms of neuroprotection, the
      complications of therapeutic hypothermia, and the future perspective of the field
      are also discussed.

PMID- 16627910
TI  - Therapy of intracranial hypertension in patients with fulminant hepatic failure.
AB  - Severe intracranial hypertension (IH) in the setting of fulminant hepatic failure
      (FHF) carries a high mortality and is a challenging disease for the critical care
      provider. Despite considerable improvements in the understanding of the
      pathophysiology of cerebral edema during liver failure, therapeutic maneuvers
      that are currently available to treat this disease are limited. Orthotopic liver
      transplantation is currently the only definitive therapeutic strategy that
      improves outcomes in patients with FHF. However, many patients die prior to the
      availability of donor organs, often because of cerebral herniation. Currently,
      two important theories prevail in the understanding of the pathophysiology of IH
      during FHF. Ammonia and glutamine causes cytotoxic cerebral injury while cerebral
      vasodilation caused by loss of autoregulation increases intracranial pressure
      (ICP) and predisposes to herniation. Although ammonia-reducing strategies are
      limited in humans, modulation of cerebral blood flow seems promising, at least
      during the early stages of hepatic encephalopathy. ICP monitoring, transcranial
      Doppler, and jugular venous oximetry offer valuable information regarding
      intracranial dynamics. Induced hypothermia, hypertonic saline, propofol sedation,
      and indomethacin are some of the newer therapies that have been shown to improve
      survival in patients with severe IH. In this article, we review the
      pathophysiology of IH in patients with FHF and outline various therapeutic
      strategies currently available in managing these patients in the critical care
      setting.

PMID- 16627911
TI  - Comment on "Validity and reliability of the DDS for severity of delirium in the
      ICU".

PMID- 16627915
TI  - Handling of thyroid follicular patterned lesions.
AB  - A novel scheme for the classification of well-differentiated thyroid tumors
      composed of follicular cells and having a follicular pattern of growth is
      presented. In addition to the two conventional categories, i.e., adenoma and
      carcinoma, this scheme includes a group of tumors "of uncertain malignant
      potential."

PMID- 16627914
TI  - Cyclooxygenase-2 and thromboxane synthase in non-endocrine and endocrine tumors:
      a review.
AB  - Prostaglandins (PG) are members of a large group of hormonally active fatty acids
      derived from free fatty acids. They are formed from arachidonic acid-the major PG
      precursor. Cyclooxygenase (COX)-1 and -2 are the rate-limiting steps in PG
      synthesis. COX-2 is overexpressed in many human non-endocrine and endocrine
      tumors including colon, breast, prostate, brain, thyroid, and pituitary. COX-2
      has an important role in angiogenesis and tumor growth. Thromboxane synthase (TS)
      catalyzes the synthesis of thromboxane A2 (TXA2), which is derived from
      arachidonic acid and prostaglandin H2 and is a vasoconstrictor and inducer of
      platelet aggregation. TXA2 stimulates tumor growth and spread of some tumors and
      TS appears to have a critical role in tumorigenesis in some organ systems. In
      this review, we examine the role of COX-2 and TS in various non-endocrine tumors,
      especially colon, breast, prostate, and brain as well as in endocrine tumors. The
      accumulating evidence points to an increasingly important role of COX-2 and TS in
      tumor progression and metastasis.

PMID- 16627916
TI  - Use and abuse of frozen section in the diagnosis of follicular thyroid lesions.
AB  - The role of intraoperative frozen section in certain organ systems such as the
      thyroid continues to be problematic. In many cases, diagnoses are deferred or
      nonhelpful--"follicular lesion." In the modern era, the widespread use of
      preoperative aspiration biopsy has allowed for more careful selection of patients
      who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA)
      biopsy diagnosis can be definitive or can guide the specific surgical procedure.
      The literature supports our approach, which is summarized as follows:
      Intraoperative consultation is not needed on the intrathyroidal nodule if a
      preoperative FNA was definitive for papillary carcinoma. Frozen section is of no
      value in the intraoperative diagnosis of lesions diagnosed on FNA as "follicular
      neoplasm" or "Hurthle cell neoplasm" because the characterization of these
      lesions requires detailed analysis of the tumor capsule for the demonstration of
      capsular and/or vascular invasion--an analysis that is not practical in the
      intraoperative setting. Finally, intraoperative consultation including frozen
      section and intraoperative cytologic examination is most useful in those cases
      that are diagnosed as suspicious for papillary carcinoma by FNA, because the
      assessment of nuclear features needed for the definitive diagnosis is possible
      with intraoperative techniques in a significant number of cases.

PMID- 16627917
TI  - The role of immunohistochemical markers in the diagnosis of follicular-patterned
      lesions of the thyroid.
AB  - Thyroid nodules are extremely common in the general population. The differential
      diagnosis includes numerous entities, non-neoplastic and neoplastic, benign and
      malignant. However, the diagnosis of follicular-patterned lesions remains an area
      fraught with controversy and diagnostic criteria are highly variable. It is,
      therefore, a field in need of objective, scientific markers that better
      characterize these lesions than has been possible by classical morphology. A
      number of candidates have been proposed. No single marker can identify all
      malignant follicular-patterned lesions, however, various combinations have been
      proposed. They include HBME-1, high molecular weight cytokeratins and ret,
      galectin-3 and TPO, galectin-3, fibronectin-1, CITED-1, HBME-1, and CK19.
      Advances in our understanding of the molecular basis of thyroid cancer will allow
      the identification of new markers and more accurate characterization of specific
      subtypes of neoplasia and malignancy. As new markers are characterized and
      validated, directed by molecular profiling of thyroid lesions with characteristic
      morphology, behavior, and outcome, they will become available as routine
      immunohistochemical markers that will provide a more accurate, scientific, and
      clinically relevant consultation report from the pathologist for cytology and
      surgical pathology procedures. Application of these markers will enhance the
      diagnosis of thyroid nodules and better guide the management of patients with
      these lesions.

PMID- 16627918
TI  - Understanding the genotype of follicular thyroid tumors.
AB  - Tumors of the thyroid with a follicular growth pattern are controversial and can
      be diagnostically challenging for the pathologist. This group of tumors includes
      both follicular derived lesions (adenomas and carcinomas) and papillary carcinoma
      (follicular variant of papillary carcinoma). H&E morphology has classically been
      the gold standard for diagnosis. In the past several decades, however, several
      important molecular markers have been identified that may be unique to different
      types of thyroid carcinomas. These include the translocations RET/PTC and PAX8
      PPARgamma and point mutations in the BRAF and RAS genes. Other molecular events
      in tumor suppressor genes may be useful for diagnosis of these tumors as well.
      None of the mutational markers are very sensitive, and there is some question
      regarding specificity for malignancy, because mutations have also been described
      in histologically benign tumors. However, with increasing availability of
      molecular testing for the general pathologist, a molecular testing panel used in
      conjunction with the H&E morphology and immunohistochemical stains may become
      useful in the clinical setting for the diagnosis of thyroid tumors.

PMID- 16627919
TI  - Papillary carcinoma of thyroid: A 30-yr clinicopathological review of the
      histological variants.
AB  - Many histological variants of PTC have been described and some are known to have
      prognostic significance. However, their relative frequencies and associated
      clinicopathological features in a large cohort of patients with PTC treated at a
      single institution have seldom been documented. We reclassified 1035 malignant
      thyroid tumors treated in a 30-yr study period, into variants of PTC according to
      current histological criteria and analyzed their features. Six hundred and fifty
      two patients (153 men; 499 women) with PTC were identified. PTC accounted for
      72.8% of primary thyroid cancers. Conventional papillary carcinoma (n = 300)
      accounted for 46% of PTC and papillary microcarcinoma 27.8% (n = 181). The
      frequencies of the common histological variants were follicular (17.6%, n =115),
      tall cell (4%, n = 26), and diffuse sclerosing (1.8%, n = 12). Uncommon
      histological variants including solid (n = 5), diffuse follicular (n = 5),
      papillary carcinoma with focal insular component (n = 3), columnar cell (n = 2),
      papillary carcinoma with fasciitis-like stroma (n = 2), and oncocytic (n = 1)
      were also noted. Histological variants of PTC had different age presentation,
      tumor size, frequencies of lymph node metastases, calcification, metaplastic
      bone, and psammoma bodies, when compared with conventional PTC. We conclude that
      a high prevalence of different variants of PTC with distinct clinicopathological
      features can be documented. Recognition of these histological variants may be
      important for better management of patients with PTC.

PMID- 16627920
TI  - Diffuse sclerosing variant of papillary thyroid carcinoma: a clinicopathologic
      and immunophenotypic analysis of 22 cases.
AB  - BACKGROUND: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV
      PTC) is an uncommon tumor making up about 2% of all papillary thyroid carcinomas.
      Previous studies have not comprehensively evaluated these tumors in a large
      series of patients. DESIGN: Twenty-two cases of DSV-PTC diagnosed between 1970
      and 2000 were identified in the files of the AFIP. Histologic and
      immunohistochemical features were evaluated and patient follow-up was obtained.
      RESULTS: The tumors affected 14 females and 8 males, aged 6 to 49 yr (mean, 18
      yr), with males presenting at a mean older age than females (24 vs 14 yr).
      Symptoms included an enlarging mass in the thyroid, present for a mean of 9.5 mo.
      While a dominant tumor was identified in a single lobe, bilateral disease was
      common (n = 16). The dominant mass ranged in size from 1.7 to 5.8 cm in diameter
      (mean, 3.8 cm). Histologically, all cases demonstrated a papillary carcinoma
      (conventional, solid, or follicular pattern) diffusely involving the gland.
      Extrathyroidal extension, lymphocytic thyroiditis, squamous metaplasia, increased
      fibrosis/sclerosis, and psammoma bodies were present to a variable degree. Both
      the papillary carcinoma and squamous metaplasia cells were strongly
      immunoreactive with CK19, thyroglobulin, and TTF-1. An increased number of S-100
      protein immunoreactive dendritic cells were recognized. p53 was increased (>15%)
      in the tumor cells in 12 patients, while Ki-67 was increased in the tumor cells
      in two patients. Perithyroidal and cervical lymph node metastasis occurred in 18
      (82%) patients. All metastases demonstrated histologic features similar to the
      primary. Complete resection (thyroidectomy in 18 patients) with lymph node
      dissection, yielded a 95% 5-yr survival without evidence of disease. One patient
      died of disease after a malignant transformation of the squamous metaplasia into
      squamous cell carcinoma. CONCLUSIONS: The recognition of DSV-PTC can be made with
      the following features: classic to solid foci of PTC, lymphocytic thyroiditis,
      squamous metaplasia, increased fibrosis, and innumerable psammoma bodies. DSV-PTC
      is more biologically aggressive than conventional PTC, but the patients' survival
      is not significantly different. This diagnosis should lead the clinician to
      aggressively manage these patients (thyroidectomy and lymph node dissection) in
      an effort to achieve an excellent long-term clinical outcome.

PMID- 16627921
TI  - Cost-effectiveness of fine-needle-aspiration cytology of thyroid nodules with
      intranodular vascular pattern using two different needle types.
AB  - OBJECTIVE: To compare the cytological findings of hypoechoic thyroid nodules with
      intranodular vascular pattern (pattern II) obtained by two different needles
      (Neolus 25 gauge, Chemil, Wenzhou, China vs Yale Spinal 25 gauge, Becton
      Dickinson, Madrid, Spain) in euthyroid patients and to evaluate their cost
      effectiveness. METHODS: From January 2001 to December 2003, 480 euthyroid
      patients with a hypoechoic thyroid nodule pattern II were referred for US-FNAC.
      The nodules were alternatively evaluated by Neolus or by Yale Spinal with the
      stylet (YS+) or without the stylet (YS-), in order to evaluate if the cytological
      results could be due to the presence of the stylet or to the different length of
      the two needles. For each nodule two passes were performed and the material was
      obtained by capillary action. Material was smeared on slides, fixed, and stained
      by Papanicolaou techniques. Cytological specimens were evaluated in blind by the
      same experienced cytopathologist. RESULTS: Inadequate cytological specimens
      because of blood contamination were present in 30 (18.7%) samples by Neolus
      needle and in 22 (13.8%) by YS- compared to only 5 (3.1%) by YS+. In 6 (20%)
      cases of the 30 repeated US-FNAC by Neolus and in 4 (18%) of the 22 US-FNAC by YS
      , material remained inadequate for diagnosis because of blood contamination. All
      the five repeated samples obtained by YS+ became adequate for diagnosis and
      resulted benign nodules. Direct costs of US-FNAC procedure are currently 72.30
      Euro including cytological examination. The cost of Neolus and Yale needles is
      0.19 Euro and 3.0 Euro, respectively. The estimated total cost to obtain a
      cytological diagnosis by a Neolus needle (160 + 30 repeated US-FNAC) was 13809.2
      Euro vs 12919.5 Euro by Yale Spinal needle (160 + 5 repeated US-FNAC).
      CONCLUSION: This study demonstrates that the use of Yale Spinal needles greatly
      reduces inadequate cytological specimens, and therefore limits both direct and
      indirect costs.

PMID- 16627922
TI  - Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression
      of the vascular endothelial growth factor (VEGF) and endostatin.
AB  - Craniopharyngiomas are benign tumors of the sellar region generally associated
      with endocrine abnormality and often locally aggressive. Several studies have
      demonstrated that angiogenesis or neovascularization plays an important role in
      tumoral growth. The microvascular density (MVD) of craniopharyngiomas was
      determined in tumor tissue samples from a reference neurosurgery center located
      in southern Brazil using immunohistochemical methods for two endothelial markers,
      CD34 and CD105 (endoglin). In addition, tissue expression was determined for an
      angiogenesis stimulatory factor and for one of its inhibitors, the vascular
      endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell
      immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD
      determined using CD105 antigen was significantly lower than the results obtained
      by using CD34 antigen. There was no association between the two endothelial
      markers and tumor extension. The epithelial component showed different degrees of
      immunoreactivity for VEGF and endostatin in all samples analyzed. We were not
      able to establish a relationship between angiogenesis in craniopharyngiomas and
      tumor extension with the endothelial markers used in this study. The investigated
      vascularization stimulatory and inhibitory factors showed no relation with MVD.
      We believe that CD105 antigen can be a more specific endothelial marker for tumor
      angiogenesis than CD34 antigen.

PMID- 16627923
TI  - Malignant paraganglioma of the urinary bladder: Immunohistochemical study of
      prognostic indicators.
AB  - Using various immunohistochemical markers, the objective of our study was to
      assess whether correlation exists between growth potential of paraganglioma
      (pheochromocytoma) cells and formation of metastasis. The patient was a 28-yr-old
      man who presented with intermittent episodes of gross hematuria due to a mass in
      the urinary bladder. He had no constitutional symptoms to suggest paraganglioma.
      Histologic, immunohistochemical, and electron microscopic investigation of the
      surgically removed tissue proved that the tumor was a malignant paraganglioma
      with metastases in the regional lymph nodes. The immunohistochemical tests were
      not supportive of high cell proliferation index, indicating that metastases can
      develop in the absence of rapid multiplication of the tumor cells. Abnormalities
      in vascular architecture and marked expression of VEGF in the tumor cells may be
      regarded as prognostic signs to predict the formation of metastases.

PMID- 16627924
TI  - Deformability, dynamics, and remodeling of cytoskeleton of the adherent living
      cell.
AB  - A trail of evidence has led to an unexpected intersection of topical issues in
      condensed matter physics and cytoskeletal biology. On the one hand, the glass
      transition and the jammed state are two outstanding unsolved problems; such
      systems are out-of-equilibrium, disordered, and their transitions between solid
      like and liquid-like states are not understood. On the other hand, cellular
      systems are increasingly being considered as interconnected maps of protein
      interactions that are highly specific and tightly regulated but, even when such
      comprehensive maps become available, they may be insufficient to define
      biological function at the integrative level because they do not encompass
      principles that govern dynamics at intermediate (meso) scales of organization. It
      is interesting, therefore, that the cytoskeleton of the living cell shows
      physical properties and remodeling dynamics with all the same signatures as soft
      inert condensed systems, although with important differences as well. Data
      reviewed here suggest that trapping, intermittency, and approach to kinetic
      arrest represent mesoscale features of collective protein-protein interactions
      linking underlying molecular events to integrative cellular functions such as
      crawling, contraction and remodeling. Because these are crucial cell functions,
      this synthesis may offer new perspectives on a variety of disorders including
      infectious disease, cardiovascular disease, asthma and cancer.

PMID- 16627925
TI  - Effects of disturbed flow on endothelial cell function: Pathogenic implications
      of modified leukocyte recruitment.
AB  - Numerous studies have shown that intracellular signalling, transcription factor
      activation and gene expression in endothelial cells are modulated by the
      magnitude and patterns of shear stress to which they are exposed. Although these
      responses suggest that the haemodynamic environment will consequently modulate
      the ability of the endothelial cells to support leukocyte recruitment as part of
      an inflammatory response, direct evidence is quite sparse. It seems that
      disturbances of flow (such as local spatial or temporal variation or sudden
      cessation) are likely to be pathogenic co-factors, combined with mediators such
      as cytokines, oxidised lipids or hypoxia, in conditions such as atherosclerosis,
      post-surgical intimal hyperplasia and ischaemia/reperfusion injury. In fact there
      have been few experimental investigations of these scenarios that include
      measurement of leukocyte adhesion and migration. We recently demonstrated that
      the level of steady shear to which EC are exposed has a powerful effect on their
      ability to support cytokine-induced leukocyte adhesion and migration. However,
      more combined studies of flow and agonist-mediated responses, with functional
      readouts, appear necessary if we are to develop a better understanding of the
      mechanisms pre-disposing to vascular inflammatory responses and pathology.

PMID- 16627926
TI  - Micropatterned polymer surfaces improve retention of endothelial cells exposed to
      flow-induced shear stress.
AB  - The use of synthetic polymeric vascular grafts is limited by the thrombogenecity
      of most biomaterials. Efforts to reduce thrombogenicity by seeding grafts with
      endothelial cells, the natural non-thrombogenic lining of blood vessels, have
      been thwarted by flow-induced cell detachment. We hypothesized that by creating
      well-defined micro-textured patterns on a surface, fluid flow at the surface can
      be altered to create discrete regions of low shear stress. We further
      hypothesized that, due to reduced shear stress, these regions will serve as
      sanctuaries for endothelial cells and promote their retention. To test these
      hypotheses, well-defined micro-textured polyurethane (PU) surfaces consisting of
      arrays of parallel 95-micron wide and 32-micron deep channels were created using
      an etched silicon template and solvent casting techniques. Based on computational
      fluid dynamics, under identical bulk flow conditions, the average local shear
      stress in the channels (46 dyn/cm2) was 28% lower than unpatterned surfaces (60
      dyn/cm2). When PU surfaces pre-seeded with endothelial cells (EC) were exposed to
      the same bulk flow rate, EC retention was significantly improved on the
      micropatterned surfaces relative to un-patterned surfaces (92% vs. 58%
      retention).

PMID- 16627927
TI  - Blood rheology of Weddell seals and bowhead whales.
AB  - Red blood cell (RBC) aggregation and blood viscosity are important determinants
      of in vivo blood flow dynamics and, in marine mammals, these parameters may
      impact diving physiology by altering blood oxygen delivery during the diving
      response. Weddell seals are superb divers and exhibit age-related patterns in
      blood oxygen chemistry and diving ability. By contrast, bowhead whales are not
      long duration divers, and little is known of their blood properties relative to
      diving. The present study was designed to compare rheological characteristics of
      blood from Weddell seal pups, Weddell seal adults, and from adult bowhead whales:
      blood viscosity and RBC aggregation in plasma and in polymer solutions (i.e., RBC
      "aggregability") were measured. Salient findings included: (1) significant 4- to
      8-fold greater aggregation in blood from adult seals compared with pups and human
      subjects; (2) 2-to 8-fold greater aggregation in bowhead whale blood compared
      with human blood; (3) compared to human red cells, enhanced RBC aggregability of
      RBC from adult seals and whales as determined by their greater aggregation in
      polymer solutions; (4) increasing RBC aggregation and aggregability of seal pup
      blood over a seven day period following birth; (5) significantly greater blood
      viscosity for adult seals compared with pups at both native and standardized
      hematocrits. These results indicate that, for both species, hemorheological
      parameters differ markedly from those of humans, and suggest progressive changes
      with seal age; the physiological implications of these differences have yet to be
      fully defined.

PMID- 16627928
TI  - An in vitro model for analysing neutrophil migration into and away from the sub
      endothelial space: Roles of flow and CD31.
AB  - To model the later stages of neutrophil migration into tissue, we developed an
      assay in which human umbilical vein endothelial cells (HUVEC) were cultured on
      porous filters, treated with the inflammatory cytokine tumour necrosis factor
      alpha (TNF), and then incorporated in a flow chamber. Video-microscopic
      observations were made of neutrophils as they were perfused over the HUVEC. When
      3 microm pore filters were used (as opposed to 0.4 microm pore filters),
      neutrophils could be observed to migrate not only through the endothelial
      monolayer but also through the filter within minutes. The proportion of adherent
      neutrophils migrating through the endothelial monolayer and velocity of migration
      underneath it, were similar on the different filters, and also when neutrophils
      were perfused over cultures in glass capillaries, or settled on HUVEC cultured in
      standard plastic dishes. However, neutrophils migrated through HUVEC/filter
      constructs more rapidly in the flow chamber than in a standard, static, Transwell
      system, even though the velocities of migration under HUVEC were similar when
      directly observed under flow or static conditions. A function-blocking antibody
      against CD31 did not alter movement through the endothelial monolayer or the
      filter in the new flow system, but did reduce the migration velocity of
      neutrophils underneath the HUVEC (by 24%). Thus, we have developed a method for
      following each stage of neutrophil migration, including exit from the sub
      endothelial space, and shown how they may be modified by applied fluid shear
      stress and blockade of a regulatory adhesion molecule.

PMID- 16627929
TI  - Electrophysiological demonstration of Na+/Ca2+ exchange in bovine articular
      chondrocytes.
AB  - Altered fluxes of Ca2+ across the chondrocyte membrane have been proposed as one
      pathway by which mechanical load can modulate cartilage turnover. In many cells,
      Na+/Ca2+ exchange (NCX) plays a key role in Ca2+ homeostasis, and recent studies
      have suggested it is operative in articular chondrocytes. In this study, an
      electrophysiological characterisation of NCX in articular bovine chondrocytes has
      been performed, using the whole-cell patch clamp technique, and the effects of
      inhibitors and the transmembrane electrochemical gradients of Na+ and Ca2+ on NCX
      function have been assessed. A Ni2+-sensitive current (I(NCX)) which exhibited
      outward rectification, was elicited by a voltage ramp protocol. The current was
      also attenuated by the NCX inhibitors benzamil and KBR7943, without significant
      differences between the effect of these two compounds upon outward and inward
      currents. The Ni2+-sensitive current was modulated by changes in extracellular
      and pipette Na+ and Ca2+ in a manner characteristic of I(NCX). Measured values
      for the reversal potential differed significantly from those predicted for an
      exchanger stoichiometry of 3Na+ : 1Ca2+, implying that accumulation of
      intracellular Ca2+ (from influx or release from stores) or more than one
      transport mode is occurring. These results demonstrate the operation of NCX in
      articular chondrocytes and suggest that changes in its turnover rate, as might
      occur in response to mechanical load, may modify cell composition and thereby
      dictate cartilage turnover.

PMID- 16627930
TI  - Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration
      through a decrease in tau O-GlcNAcylation.
AB  - Neurofibrillary degeneration characterized by abnormal hyperphosphorylation and
      aggregation of tau in affected neurons is directly associated with dementia
      symptoms and plays a pivotal role in the pathogenesis of Alzheimer disease (AD)
      and related tauopathies. It is well established that brain glucose
      uptake/metabolism is impaired in AD, but how this impairment contributes to the
      disease is unknown. We recently found that tau in human brain is also modified by
      O-GlcNAcylation in addition to phosphorylation and that the former negatively
      regulates the latter. On the basis of these findings, we propose a novel
      hypothesis that the impaired glucose uptake/metabolism contributes to AD by
      facilitating abnormal hyperphosphorylation of tau. Further studies of this
      mechanism are likely to offer a novel therapeutic target for preventing and
      treating AD.

PMID- 16627931
TI  - Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic
      Alzheimer's disease.
AB  - The cascade of Alzheimer's disease (AD) neurodegeneration is associated with
      persistent oxidative stress, mitochondrial dysfunction, impaired energy
      metabolism, and activation of pro-death signaling pathways. More recently,
      studies with human postmortem brain tissue linked many of the characteristic
      molecular and pathological features of AD to reduced expression of the insulin
      and insulin-like growth factor (IGF) genes and their corresponding receptors. We
      now demonstrate using an in vivo model of intracerebral Streptozotocin (ic-STZ),
      that chemical depletion of insulin and IGF signaling mechanisms combined with
      oxidative injury is sufficient to cause AD-type neurodegeneration. The ic-STZ
      injected rats did not have elevated blood glucose levels, and pancreatic
      architecture and insulin immunoreactivity were similar to control, yet their
      brains were reduced in size and exhibited neurodegeneration associated with cell
      loss, gliosis, and increased immunoreactivity for p53, active glycogen synthase
      kinase 3beta, phospho-tau, ubiquitin, and amyloid-beta. Real time quantitative RT
      PCR studies demonstrated that the ic-STZ-treated brains had significantly reduced
      expression of genes corresponding to neurons, oligodendroglia, and choline
      acetyltransferase, and increased expression of genes encoding glial fibrillary
      acidic protein, microglia-specific proteins, acetylcholinesterase, tau, and
      amyloid precursor protein. These abnormalities were associated reduced expression
      of genes encoding insulin, IGF-II, insulin receptor, IGF-I receptor, and insulin
      receptor substrate-1, and reduced ligand binding to the insulin and IGF-II
      receptors. These results demonstrate that many of the characteristic features of
      AD-type neurodegeneration can be produced experimentally by selectively impairing
      insulin/IGF functions together with increasing oxidative stress, and support our
      hypothesis that AD represents a neuro-endocrine disorder associated with brain
      specific perturbations in insulin and IGF signaling mechanisms, i.e. Type 3
      diabetes.

PMID- 16627932
TI  - Blueberry extract alters oxidative stress-mediated signaling in COS-7 cells
      transfected with selectively vulnerable muscarinic receptor subtypes.
AB  - Previous research has indicated that selective vulnerability to oxidative stress
      may be important in determining regional differences in functional declines in
      neuronal aging. Oxidative stress vulnerability may involve selective deficits in
      Ca2+ buffering (Ca2+ recovery time following oxotremorine application) to
      oxidative stress, determined in-part by receptor subtype with M1, M2 and M4 AChR
      showing greater oxidative stress-induced loss [via dopamine (DA) exposure for 4
      hrs] of Ca2+ recovery time than that seen in M3 or M5 cells. Deficits were
      antagonized by pre-treating M1, M2, or M4 AChR-transfected cells with blueberry
      (BB) extract. Thus, we assessed whether these differences in oxidative stress
      vulnerability might involve differential patterns of DA-induced protein kinase
      (PKCalpha, PKCgamma) and/or cyclic AMP response element binding protein (CREB)
      activation, and whether these differences might be altered by BB treatment. M1 or
      M3 AChR-transfected COS-7 cells were exposed to 1 mM DA, and activation of
      phospho-(p) mitogen-activated protein kinase (MAPK) signaling was examined by
      immunoblotting analyses. The results showed that DA increased pCREB and pPKCgamma
      for both M1- and M3-transfected cells, and BBs decreased these DA-induced
      alterations, when measured by immunoblotting techniques. Taken together these
      findings suggest that M1/M3 oxidative stress sensitivity differences may involve
      differential signaling in pMAPK and pCREB under oxidative stress conditions,
      suggesting that the native protection in these receptors against oxidative stress
      and inflammation may be derived from reduced activation. These findings also
      suggest that BB may antagonize oxidative stress effects induced by DA in M1
      transfected cells by lowering activation of pCREB, and possibly pPKCgamma.

PMID- 16627933
TI  - The brain-derived neurotrophic factor Val66Met polymorphism and rate of decline
      in Alzheimer's disease.
AB  - It is largely unknown why some patients with Alzheimer's disease (AD) decline
      cognitively more rapidly than others. Genetic differences among patients could
      influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a
      neurotrophin important in the survival neurons and in memory function. BDNF
      levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene
      modifies neuronal BDNF secretion, and affects hippocampal function and memory
      performance. We tested the hypothesis that the BDNF Val66Met polymorphism
      influences rate of cognitive decline in AD. In a sample of 149 AD patients
      followed for an average of 3.9 years, we found no effect of BDNF Val66Met
      genotype on rate of change in the Mini Mental State Examination. Results were
      similar when we excluded patients taking an acetylcholinesterase inhibitor, those
      placed in a nursing home during the study, or those with a neuropathological
      diagnosis that included AD plus an entity other than AD. We also found no
      evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype,
      which itself had no effect on rate of cognitive change. These findings suggest
      that the functional BDNF Val66Met variant is not a major determinant of rate of
      cognitive decline in AD.

PMID- 16627934
TI  - Thrombin and inflammatory proteins are elevated in Alzheimer's disease
      microvessels: implications for disease pathogenesis.
AB  - The notion that microvascular abnormalities contribute to deleterious changes in
      the Alzheimer's disease (AD) brain is supported by work from our laboratory and
      others demonstrating biochemical and functional alterations of the
      microcirculation in AD. The objective of this study is to determine whether
      levels of neurotoxic (thrombin) and inflammatory (interleukin 8 (IL-8), integrins
      alphaVbeta3 and alphaVbeta5) proteins are altered in microvessels isolated from
      AD patients compared to levels in vessels obtained from non-demented age-matched
      controls. We also evaluate in AD and control microvessels expression of the
      transcription factor hypoxia-inducible factor 1-alpha(HIF1-alpha), which
      regulates pro-inflammatory gene expression, and the regulation of HIF1-alpha
      expression by thrombin in cultured brain endothelial cells. Our results indicate
      that in AD there are high levels of expression of the neurotoxic protease
      thrombin and the inflammation-associated proteins IL-8 and alphaVbeta3 and
      alphaVbeta5 integrins. HIF1-alpha is higher in AD microvessels compared to
      control and thrombin treatment of cultured brain endothelial cells results in
      increased expression of HIF1-alpha. These data suggest that in AD the cerebral
      microcirculation is a source of neurotoxic and inflammatory mediators and as such
      contributory to pathologic processes ongoing in the AD brain.

PMID- 16627935
TI  - Time window in cholinomimetic ability to rescue long-term potentiation in
      neurodegenerating anti-nerve growth factor mice.
AB  - A deficit in cortical cholinergic synaptic transmission is a common feature of
      cognitive and behavioral impairment observed in neurodegenerative pathologies.
      AD11 transgenic mice producing blocking antibodies against Nerve Growth Factor
      (NGF) are characterized by a progressive neurodegenerative phenotype defined by
      the deposition of amyloid peptide, intracellular neurofibrillary tangles and by a
      marked cholinergic depletion. We exploited AD11 mice to develop a functional
      assay to investigate the impact of cholinergic deficit on cortical synaptic
      plasticity impairment at different neurodegenerative stages. In particular, we
      investigated the time course of long-term potentiation (LTP) impairment in
      neocortex of AD11 mice and potential rescue by acute pharmacological treatment
      with Acetylcholine (ACh) or the cholinergic agonist Galantamine (GAL). We showed
      that LTP starts being absent in AD11 mice at 2 months, an age corresponding to
      early neurodegenerative stage characterized by the first observed decrease in
      number of basal forebrain cholinergic neurons (BFCNs) without overt cortical
      neurodegeneration. We demonstrated that acute ACh or GAL treatment fully reverts
      LTP impairment in 2 month old AD11 mice. In contrast, cholinergic treatment
      failed to recover synaptic plasticity deficit in aged (9-10 months) AD11 mice
      characterized by a severe cortical neurodegeneration.

PMID- 16627936
TI  - The management of agitation in demented patients with propranolol.
AB  - Congress and the FDA have strongly suggested that tranquilizers and
      antipsychotics not be used in agitated demented frail elderly patients. The
      medical profession has not moved away from the tradition of antipsychotic
      sedation of such patients. Use of 'modern second generation low dose'
      antipsychotics continue to be the standard of care. Propranolol, a non-selective
      beta-blocker with good penetration of the CNS, is a reasonable and safe
      alternative to sedatives and antipsychotics. Anti-dementia drugs are
      complementary to propranolol. A case study which contrasts the two pharmacologic
      approaches is detailed. A method of estimating delirium-agitation risk in
      dementia patients (DRN method) is described.

PMID- 16627937
TI  - Alzheimer's disease and head circumference.
AB  - OBJECTIVE: Larger brains may contain more neurons and synaptic connections,
      providing a greater reserve against cognitive decline in Alzheimer's disease
      (AD). Larger head circumference (HC) may therefore be associated with later
      detection and diagnosis of AD. We investigated HC in nondemented individuals and
      AD patients using cross-sectional and prospective analyses. METHODS: The cross
      sectional analysis compared mean HC between 592 AD patients and 459 nondemented
      controls. Prospective analysis was based on the same initially normal controls
      who were followed longitudinally for conversion to dementia. Diagnosis of AD was
      made by neurologists using NINDS-ADRDA criteria. RESULTS: When compared to AD
      patients, controls had a significantly larger mean HC by 0.58 cm in men and by
      0.31 cm in women, but these differences were no longer significant after
      adjustment for age and years of education. HC varied inversely with age and
      directly with years of education but did not vary with presence/absence of
      dementia in first-degree relatives or with apolipoprotein-E (ApoE) genotype. In
      the prospective analysis, the hazard ratio for time to conversion to AD was not
      significant for HC when adjusted for age at entry, ApoE allele status, family
      history of dementia, gender, and years of education. ApoE allele status, first
      degree relative with dementia, and baseline age conferred an increased risk for
      conversion to AD, consistent with other studies. CONCLUSIONS: We observed a
      smaller HC in AD patients compared to nondemented individuals, but AD per se
      accounted for little of this difference. HC was not a statistically significant
      predictor for conversion to AD in our longitudinal group.

PMID- 16627938
TI  - Combining experimental data for structure determination of flexible multimeric
      macromolecules by molecular replacement.
AB  - A major effort has been made by the structural biology community to develop user
      friendly software for the use of biologists. However, structural projects become
      more and more challenging and their solution often relies on a combination of
      information from various sources. Here, it is described how X-ray data, normal
      mode analysis (NMA) and electron-microscopy (EM) data can be successfully
      combined in order to obtain a molecular-replacement (MR) solution for crystal
      structures containing multimeric molecules. NMA is used to simulate
      computationally the inherent internal flexibility of the monomer and thus
      enhance, together with the crystal noncrystallographic symmetry (NCS), the MR
      capabilities. NCS is also used to obtain a reliable EM reconstruction, which is
      then employed as a filter to construct oligomers starting from monomers. The
      feasibility of the direct use of EM reconstructions as a template for MR when the
      X-ray and EM data resolutions overlap is also discussed.

PMID- 16627939
TI  - Structure of T4moC, the Rieske-type ferredoxin component of toluene 4
      monooxygenase.
AB  - The structure of the Rieske-type ferredoxin (T4moC) from toluene 4-monooxygenase
      was determined by X-ray crystallography in the [2Fe-2S](2+) state at a resolution
      of 1.48 A using single-wavelength anomalous dispersion phasing with the [2Fe-2S]
      center. The structure consists of ten beta-strands arranged into the three
      antiparallel beta-sheet topology observed in all Rieske proteins. Trp69 of T4moC
      is adjacent to the [2Fe-2S] centre, which displaces a loop containing the
      conserved Pro81 by approximately 8 A away from the [2Fe-2S] cluster compared with
      the Pro loop in the closest structural and functional homolog, the Rieske-type
      ferredoxin BphF from biphenyl dioxygenase. In addition, T4moC contains five
      hydrogen bonds to the [2Fe-2S] cluster compared with three hydrogen bonds in
      BphF. Moreover, the electrostatic surface of T4moC is distinct from that of BphF.
      These structural differences are identified as possible contributors to the
      evolutionary specialization of soluble Rieske-type ferredoxins between the diiron
      monooxygenases and cis-dihydrodiol-forming dioxygenases.

PMID- 16627940
TI  - Structure of the catalytic nucleotide-binding subunit A of A-type ATP synthase
      from Pyrococcus horikoshii reveals a novel domain related to the peripheral
      stalk.
AB  - H(+)-transporting ATP synthase is a multi-subunit enzyme involved in the
      production of ATP, which is an essential molecule for living organisms as a
      source of energy. Archaeal A-type ATPase (A-ATPase) is thought to act as a
      functional ATP synthase in archaea and is thought to have chimeric properties of
      F-ATPase and V-ATPase. Previous structural studies of F-ATPase indicated that the
      major nucleotide-binding subunits alpha and beta consist of three domains. The
      catalytic nucleotide-binding subunit A of V/A-ATPase contains an insertion of
      about 90 residues which is absent from the F(1)-ATPase beta subunit. Here, the
      first X-ray structure of the catalytic nucleotide-binding subunit A of an A(1)
      ATPase is described, determined at 2.55 A resolution. A(1)-ATPase subunit A from
      Pyrococcus horikoshii consists of four domains. A novel domain, including part of
      the insertion, corresponds to the 'knob-like structure' observed in electron
      microscopy of A(1)-ATPase. Based on the structure, it is highly likely that this
      inserted domain is related to the peripheral stalk common to the A- and V
      ATPases. The arrangement of this inserted domain suggests that this region plays
      an important role in A-ATPase as well as in V-ATPase.

PMID- 16627941
TI  - On the role of the R configuration of the reaction-intermediate isostere in HIV-1
      protease-inhibitor binding: X-ray structure at 2.0 A resolution.
AB  - Peptidomimetic inhibitors of human immunodeficiency virus-1 protease are
      successful lead substances for the development of virostatic drugs against HIV as
      the causative agent of acquired immunodeficiency syndrome (AIDS). The
      hydroxyethylamine isostere of the proteolytic cleavage intermediate provides a
      suitable replacement for the peptide bond. A series of acyclic pseudopeptide
      inhibitors with the hydroxyethylamine isostere varying in chiral carbon
      configuration and P'2 residue type were structurally analysed by single-crystal X
      ray crystallography. The compounds inhibit HIV protease with subnanomolar
      inhibition constants and block viral replication in tissue cultures. Here, the
      structure of such a complex with the R configuration of the isosteric group (PDB
      code 1zsf) is presented together with newly available synchrotron data for a
      complex with the S stereoisomer of the inhibitor (PDB code 1zsr). Comparison of
      the structure and binding with other complexes of HIV-1 protease and similar
      inhibitors contributes to the understanding of how these molecules bind to the
      wild-type form of this enzyme. The hydroxy group of the R stereoisomer interacts
      with one of the catalytic aspartic acids by a short hydrogen bond with rather
      extreme geometry. The change of configuration of the chiral carbon bearing the
      hydroxyl from S to R does not influence the inhibition efficiency in this case.

PMID- 16627942
TI  - Resolution improvement of X-ray diffraction data of crystals of a vesicular
      stomatitis virus nucleocapsid protein oligomer complexed with RNA.
AB  - Vesicular stomatitis virus (VSV) is a non-segmented negative-stranded RNA virus.
      The nucleocapsid (N) protein of VSV is found tightly associated with the viral
      genomic RNA and this complex serves as the template for transcription and
      replication. A method for the soluble expression of the N protein in Escherichia
      coli has previously been reported. An N protein-RNA oligomer was isolated from
      this system, the stoichiometry of which was determined to be ten molecules of the
      N protein bound to approximately 90 nucleotides of RNA. Here, the crystallization
      of this protein-nucleic acid complex is presented. The crystals belong to space
      group P2(1)2(1)2, with unit-cell parameters a = 165.65, b = 235.35, c = 75.71 A
      and a diffraction limit of 6 A. Self-rotation function analysis has shown the
      oligomer to have tenfold rotational symmetry. In a search to identify heavy-atom
      derivatives, uranyl acetate was discovered to stabilize the crystals, giving them
      an increase in diffraction limits to beyond 2.9 A. Based on the internal symmetry
      of the oligomer, the size of the oligomer determined previously by negative
      stained electron microscopy, the space-group symmetry and packing considerations,
      the packing arrangement in the crystal has been determined.

PMID- 16627943
TI  - I222 crystal form of despentapeptide (B26-B30) insulin provides new insights into
      the properties of monomeric insulin.
AB  - Despentapeptide (des-B26-B30) insulin (DPI), an active modified insulin, has been
      crystallized in the presence of 20% acetic acid pH 2. A crystal structure
      analysis to 1.8 A spacing (space group I222) revealed that the DPI molecule,
      which is unable to make beta-strand interactions for physiological dimer
      formation and is apparently monomeric in solution, formed an alternative lattice
      generated dimer. The formation of this dimer involved interactions between
      surfaces which included the B9-B19 alpha-helices (usually buried by the dimer
      dimer contacts within the native hexamer). The two crystallographically
      independent molecules within the dimer were essentially identical and were
      similar in conformation to T-state insulin as seen in the T(6) insulin hexamer.
      An unusual feature of each molecule in the dimer was the presence of two
      independent conformations at the B-chain C-terminus (residues B20-B25). Both
      conformations were different from that of native insulin, involving a 3.5 A
      displacement of the B20-B23 beta-turn and a repositioning of residue PheB25 such
      that it made close van der Waals contact with the main body of the molecule,
      appearing to stabilize the B-chain C-terminus.

PMID- 16627944
TI  - The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin.
AB  - Systemic deposition of transthyretin (TTR) amyloid fibrils is always observed in
      familial amyloidotic polyneuropathy, senile systemic amyloidosis and familial
      amyloidotic cardiomyopathy patients. Destabilization of the molecule leads to a
      cascade of events which result in fibril formation. The destabilization of a
      native protein with consequent conformational changes appears to be a common link
      in several human amyloid diseases. Intensive research has been directed towards
      finding small molecules that could work as therapeutic agents for the
      prevention/inhibition of amyloid diseases through stabilization of the native
      fold of the potentially amyloidogenic protein. This work provides insight into
      the structural determinants of the highly stabilizing effects of 2,4
      dinitrophenol on wild-type TTR. It is also shown that similar interactions are
      established between this molecule and two highly amyloidogenic TTR variants: TTR
      L55P and TTR Y78F. In the three crystal complexes, 2,4-dinitrophenol occupies the
      two hormone-binding sites of the TTR tetramer. As a result of 2,4-dinitrophenol
      binding, the two dimers in the TTR tetramer become closer, increasing the
      stability of the protein. The three-dimensional structures now determined allow a
      comprehensive description of key interactions between transthyretin and 2,4
      dinitrophenol, a small compound that holds promise as a template for the design
      of a therapeutical drug for amyloid diseases.

PMID- 16627945
TI  - Novel versatile cryoprotectants for heavy-atom derivatization of protein
      crystals.
AB  - Determination of a suitable cryoprotectant agent condition is one of the time
      consuming processes in protein X-ray crystallography. The adaptability of two
      novel versatile cryoprotectants (oil- and water-based types) has been evaluated
      by cryodiffraction experiments using crystals of five different proteins. The
      results suggest that complementary use of both oil- and water-based
      cryoprotectants enables the successful cryoprotection of protein crystals. Since
      the versatile cryoprotectants do not contain crystallization solution, rapid and
      efficient preparation of heavy-atom derivatives is possible with these
      cryoprotectants in the presence of heavy-atom reagents. Four heavy-atom reagents
      [K(2)PtCl(4), HgCl(2), KAu(CN)(2) and K(2)Pt(CN)(4)] were examined and could be
      stored with sufficient derivatizing capabilities for over one month in the
      versatile cryoprotectants.

PMID- 16627946
TI  - Structure of a red fluorescent protein from Zoanthus, zRFP574, reveals a novel
      chromophore.
AB  - The three-dimensional structure of the red fluorescent protein (RFP) zRFP574 from
      the button polyp Zoanthus sp. (two dimers per asymmetric unit, 231 x 4 amino
      acids) has been determined at 2.4 A resolution in space group C222(1). The
      crystal structure, refined to a crystallographic R factor of 0.203 (R(free) =
      0.249), adopts the beta-barrel fold composed of 11 strands similar to that of the
      yellow fluorescent protein zYFP538. The zRFP574 chromophore, originating from the
      protein sequence Asp66-Tyr67-Gly68, has a two-ring structure typical of GFP-like
      proteins. The bond geometry of residue 66 shows the strong tendency of the
      corresponding C(alpha) atom to sp(2) hybridization as a consequence of N
      acylimine bond formation. The zRFP574 chromophore contains the 65-66 cis-peptide
      bond characteristic of red fluorescent proteins. The chromophore phenolic ring
      adopts a cis conformation coplanar with the imidazolinone ring. The
      crystallographic study has revealed an unexpected chemical feature of the
      internal chromophore. A decarboxylated side chain of the chromophore-forming
      residue Asp66 has been observed in the structure. This additional post
      translational modification is likely to play a key role in the bathochromic shift
      of the zRFP574 spectrum.

PMID- 16627947
TI  - Low-resolution ab initio phasing of Sarcocystis muris lectin SML-2.
AB  - Structural analysis of the lectin SML-2 faced difficulties when applying standard
      crystallographic phasing methods. The connectivity-based ab initio phasing method
      allowed the computation of a 16 A resolution Fourier synthesis and the derivation
      of primary structural information. It was found that SML-2 crystals have three
      dimers in the asymmetric part of the unit cell linked by a noncrystallographic
      symmetry close to translation by (0, 0, 1/3). A clear identification of the
      noncrystallographic twofold axis explains the space-group transformation from the
      primitive P2(1)2(1)2(1) to the C-centred C222(1) observed during annealing
      procedures within an N(2) cryostream for cocrystals of SML-2 and galactose.
      Related packing considerations predict a possible arrangement of SML-2 molecules
      in a tetragonal unit cell. Multiple noncrystallographic symmetries and crystal
      forms provide a basis for further image improvements.

PMID- 16627948
TI  - Structure of alcohol dehydrogenase from Entamoeba histolytica.
AB  - The structure of the apo form of alcohol dehydrogenase from a single-cell
      eukaryotic source, Entamoeba histolytica, has been determined at 1.8 A. To date,
      bacterial and archeal alcohol dehydrogenases, which are biologically active as
      tetramers, have crystallized with tetramers in the asymmetric unit. However, the
      current structure has one independent dimer per asymmetric unit and the full
      tetramer is generated by application of the crystallographic twofold symmetry
      element. This structure reveals that many of the crystallization and
      cryoprotection components, such as cacodylate, ethylene glycol, zinc ions and
      acetate, have been incorporated. These crystallization solution elements are
      found within the molecule and at the packing interfaces as an integral part of
      the three-dimensional arrangements of the tetramers. In addition, an unexpected
      modification of aspartic acid to O-carboxysulfanyl-4-oxo-L-homoserine was found
      at residue 245.

PMID- 16627949
TI  - Mutation of Gly51 to serine in the P-loop of Lactobacillus casei
      folylpolyglutamate synthetase abolishes activity by altering the conformation of
      two adjacent loops.
AB  - Based upon the three-dimensional structure of Lactobacillus casei
      folylpolyglutamate synthetase (FPGS), site-directed mutagenesis studies were
      performed on three residues associated with the ATPase site: Gly51, Ser52 and
      Ser73. Gly51 and Ser52 are at the end of the P-loop, which is involved in
      triphosphate binding. A G51S mutant enzyme and a G51S/S52T double-mutant enzyme
      were made in order to alter the FPGS P-loop to more closely resemble the
      sequences found in other ATPase and GTPase enzymes. Ser73 is on a neighboring
      loop (the Omega-loop) and precedes a proline residue found to be in a cis
      conformation. The carbonyl O atom of Ser73 is one of the protein ligands for the
      essential Mg(2+) ion involved in ATP binding and hydrolysis and the Omega-loop is
      involved in binding the folate substrate 5,10-methylenetetrahydrofolate. The
      serine residue was mutated to alanine and this is the only one of the three
      mutants which retains some FPGS activity. The structures of the G51S, G51S/S52T
      and S73A mutant proteins have been solved to high resolution, along with the
      structure of the apo wild-type FPGS. The P-loop in both the G51S and G51S/S52T
      mutant proteins remains unaltered, yet both structures show a large
      conformational rearrangement of the Omega-loop in which a cis-Pro residue has
      switched conformation to a trans-peptide. The structure of the Omega-loop is
      severely disrupted and as a consequence structural rearrangements are observed in
      the peptide linker joining the two domains of the enzyme. Magnesium binding in
      the active site is also disrupted by the presence of the serine side chain at
      position 51 and by the repositioning of the carbonyl O atom of Ser73 and a water
      molecule is bound in place of the Mg(2+) ion. The S73A mutant protein retains the
      cis-Pro configuration in the Omega-loop and the Mg(2+) site remains intact. The
      cis-Pro is also observed in the structure of the substrate-free form of FPGS
      (apoFPGS), maintained in the absence of Mg(2+) by a hydrogen-bonding network
      involving water molecules in the active site. It is only in the complete absence
      of water or Mg(2+) in the binding site that the cis-Pro switches to the trans
      conformation.

PMID- 16627950
TI  - A method for screening the temperature dependence of three-dimensional crystal
      formation.
AB  - Temperature is an important parameter controlling protein crystal growth. A new
      temperature-screening system (Thermo-screen) is described consisting of a
      gradient thermocycler fitted with a special crystallization-plate adapter onto
      which a 192-well sitting-drop crystallization plate can be mounted (temperature
      range 277-372 K; maximum temperature gradient 20 K; interval precision 0.3 K).
      The system allows 16 different conditions to be monitored simultaneously over a
      range of 12 temperatures and is well suited to conduct wide (approximately 20 K)
      and fine (approximately 3 K) temperature-optimization screens. It can potentially
      aid in the determination of temperature phase diagrams and run more complex
      temperature-cycling experiments for seeding and crystal growth.

PMID- 16627951
TI  - Structure of the inactive variant C60S of Mycobacterium tuberculosis thiol
      peroxidase.
AB  - The genome of Mycobacterium tuberculosis encodes several peroxiredoxins (Prxs)
      thought to be active against organic and inorganic peroxides. The open reading
      frame Rv1932 encodes a 165-residue thiol peroxidase (Tpx), which belongs to the
      atypical 2-Cys peroxiredoxin family. The crystal structure of the C60S mutant of
      M. tuberculosis Tpx (MtTpx) crystallized in space group P3(1)21, with unit-cell
      parameters a = 106.08, b = 106.08, c = 65.33 A. The structure has been refined to
      an R value of 17.1% (R(free) = 24.9%) at 2.1 A resolution. MtTpx is structurally
      homologous to other peroxiredoxins, including the mycobacterial AhpC and AhpE.
      The inactive MtTpx C60S mutant structure closely resembles the structure of
      Streptococcus pneumoniae Tpx (SpTpx) and thus represents the reduced enzyme
      state. The mutated active-site serine is electrostatically linked to Arg130 and
      hydrogen bonded to Thr57, practically identical to the cysteine in SpTpx. A
      cocrystallized acetate molecule mimics the position of the substrate and
      interacts with Ser60, Arg130 and Thr57.

PMID- 16627952
TI  - Inhibitory effects of CIDR-based ovulation-synchronization protocols on uterine
      PGF2alpha secretion at the following luteal phase in early postpartum non-cycling
      beef cows.
AB  - We investigated whether CIDR-based ovulation-synchronization protocols inhibit
      secretion of prostaglandin (PG) F2alpha from the uterus in the following luteal
      phase in non-cycling beef cows. Ten early (a month) postpartum non-cycling
      Japanese Black beef cows were treated with (1) Ovsynch (GnRH analogue on Day 0,
      PGF2alpha analogue on Day 7, and GnRH analogue on Day 9; n=3), (2) Ovsynch+CIDR
      (Ovsynch protocol plus a CIDR for 7 days from Day 0; n=4), or (3) estradiol
      benzoate (EB) Ovsynch+CIDR (EB on Day 0 in lieu of the first GnRH treatment
      followed by the Ovsynch+CIDR protocol; n=3). An oxytocin challenge was
      administered on Day 24 to examine uterine PGF2alpha secretion. Plasma
      concentrations of 13,14-dihydro-15-keto- PGF2alpha were lower at 30-120 min after
      oxytocin administration in the Ovsynch+CIDR group and 75 min after administration
      in the EB Ovsynch+CIDR group than in the Ovsynch group (P<0.05). Plasma
      progesterone concentrations were higher from Days 1 to 7 in the Ovsynch+CIDR
      group and from Days 1 to 5 in the EB Ovsynch+CIDR group than in the Ovsynch group
      (P<0.05). The progesterone concentrations were higher on Days 27 and 29 in both
      CIDR-treated groups than in the Ovsynch group (P<0.05). In conclusion, in non
      cycling beef cows, CIDR-based ovulation-synchronization protocols inhibit uterine
      PGF2alpha secretion in the following luteal phase and prevent premature
      luteolysis as is seen with the Ovsynch protocol.

PMID- 16627953
TI  - TCDD increases inhibin A production by human luteinized granulosa cells in vitro.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic of the halogenated
      dioxins and one of the most poisonous substances known to man. The major toxic
      effects of TCDD on reproduction are decreased fertility and diminished ability to
      maintain a pregnancy. Granulosa cells obtained from hormonally stimulated women
      participating in an in-vitro fertilization program were cultured with 3.1
      femtomolar, 3.1 picomolar and 3.1 nanomolar TCDD. While inhibin B production was
      not altered, inhibin A production increased significantly after 4 hours of
      exposure to both nanomolar and micromolar TCDD concentrations. By 8 hours of
      exposure to these concentrations of dioxin, human luteinizing granulosa cells
      exhibited a pronounced increase in inhibin A, nearly quadrupling secretion from
      unexposed control cells. TCDD continued to increase inhibin A secretion at the
      picomolar concentration at 24 and 36 hours. It is conceivable that TCDD may act
      at the ovary to augment inhibin A secretion, thereby reducing FSH-stimulable
      estrogen secretion by granulosa cells.

PMID- 16627954
TI  - Analysis of the function of activin betaC subunit using recombinant protein.
AB  - Activins, TGF-beta superfamily members, have multiple functions in a variety of
      cells and tissues. Additional activin beta subunit genes, betaC and betaE, have
      been identified in humans and rodents. To explore the role of activin betaC
      subunit, we generated recombinant human activin C using Chinese hamster ovary
      cells. Recombinant activin C from the conditioned medium was purified by
      consecutive hydrophobic, size-exclusion, and high performance liquid
      chromatography. SDS-PAGE and Western blot analysis of the purified protein
      revealed that activin C formed disulfide bridges. However, activin C had no
      effect on the proliferation of cultured liver cells. Furthermore, there were no
      significant differences in erythroid differentiation and follicle stimulating
      hormone secretion in vitro. It was also shown that immunoreactive bands indicated
      the hetrodimer of activin betaC, and inhibin alpha subunits were detected in the
      conditioned medium from the activin C-producing cells, which were stably
      transfected with inhibin alpha subunit cDNA. This suggests that activin betaC
      subunit may have been present and that it may exert its effect as inhibin C.

PMID- 16627955
TI  - Relationship between the first ovulation within three weeks postpartum and
      subsequent ovarian cycles and fertility in high producing dairy cows.
AB  - The aim of this study was to investigate the relationship between the first
      ovulation within 3 weeks postpartum and subsequent ovarian cycles and fertility
      in high producing dairy cattle in Hokkaido, Japan. In Experiment 1, 110 cows (44
      primiparous and 66 multiparous) were used to determine the effects of the first
      ovulation within 3 weeks postpartum on subsequent ovarian cycles. Milk samples
      were collected twice weekly from 7 to 100 days postpartum. The first ovulation
      was identified by an increase in milk progesterone (P4) to more than 1 ng/ml
      within 3 weeks postpartum. The numbers of cows showing ovulation and anovulation
      within 3 weeks postpartum were 31 (70.5%) and 13 (29.5%) in the primiparous cows
      and 35 (53.0%) and 31 (47.0%) in the multiparous cows, respectively. The patterns
      of ovarian resumption after calving were classified into two types (normal
      ovarian cycles and abnormal ovarian cycles) on the basis of milk P4
      concentrations. Initiation of normal ovarian function in cows ovulated within 3
      weeks postpartum occurred earlier than in anovulated cows regardless of the
      number of calvings (primiparous, 27.8 days vs. 44.4 days; multiparous, 30.6 days
      vs. 55.7 days; P<0.01). Out of the multiparous cows that ovulated within 3 weeks
      postpartum, initiation of normal ovarian function followed by a normal luteal
      phase was earlier than when it was followed by an abnormal luteal phase (25.5
      days vs. 40.4 days; P<0.05). Milk P4 concentrations after the first ovulation
      were lower than those after the second ovulation in both the primiparous and
      multiparous cows (P<0.05). In Experiment 2, 22 multiparous cows were used to
      determine the effects of the first ovulation within 3 weeks postpartum on
      subsequent fertility. Blood samples were collected once a week from 0 to 3 weeks
      postpartum. The interval from parturition to first service in ovulated cows was
      shorter than in anovulated cows (68.4 days vs. 94.8 days; P<0.05). The conception
      rate by 100 days after calving tended to be higher in ovulated cows than in
      anovulated cows (50.0% vs. 16.7%, P=0.09). In conclusion, our data strongly
      suggests that ovulation within 3 weeks postpartum is a crucial phenomenon for
      subsequent resumption of ovarian function and conception, and thus it can be used
      as an index of subsequent reproductive performance.

PMID- 16627956
TI  - In memoriam of Rudolf virchow: a historical retrospective including aspects of
      inflammation, infection and neoplasia.
AB  - Rudolf Ludwig Carl Virchow (1821-1902) studied medicine and received his academic
      degree 'Dr. med.' in 1843. In 1856 he was appointed as head of the institute of
      pathology at the University of Berlin. In 1859, he became a member of the Berlin
      town council and later additionally a member of the Prussian and the German
      parliament. With his probably most important publication 'Cellularpathologie' he
      introduced pathology to a cellular rationale. This was the major basis for his
      research in oncology. Virchow further studied aspects of inflammation, despite
      only few links to tumor pathology were drawn. The few links from infection and
      inflammation to tumor pathology have almost been forgotten or ignored and have
      never been evaluated and discussed sufficiently. Virchow recognized that
      inflammation is a pre-disposing factor for tumor genesis. Furthermore, infectious
      diseases such as syphilis and tuberculosis had elements of a 'tumor process' and
      were therefore often difficult or impossible to separate from a 'genuine' tumor
      process, which was recognized by him. He further tried to explain tumor
      dissemination by an 'infectious' process. Additionally, there were ideas for a
      coherent explanation of tumor etiology in form of a common bacterial pathogen
      ('Krebsbacillus').

PMID- 16627957
TI  - Aneuploidy and cancer: from correlation to causation.
AB  - Conventional genetic theories have failed to explain why cancer (1) is not found
      in newborns and thus not heritable; (2) develops only years to decades after
      'initiation' by carcinogens; (3) is caused by non-mutagenic carcinogens; (4) is
      chromosomally and phenotypically 'unstable'; (5) carries cancer-specific
      aneuploidies; (6) evolves polygenic phenotypes; (7) nonselective phenotypes such
      as multidrug resistance, metastasis or affinity for non-native sites and
      'immortality' that is not necessary for tumorigenesis; (8) contains no
      carcinogenic mutations. We propose instead that cancer is a chromosomal disease:
      Accordingly, carcinogens initiate chromosomal evolutions via unspecific
      aneuploidies. By unbalancing thousands of genes aneuploidy corrupts teams of
      proteins that segregate, synthesize and repair chromosomes. Aneuploidy is thus a
      steady source of karyotypic-phenotypic variations from which, in classical
      Darwinian terms, selection of cancer-specific aneuploidies encourages the
      evolution and subsequent malignant 'progressions' of cancer cells. The rates of
      these variations are proportional to the degrees of aneuploidy, and can exceed
      conventional mutation by 4-7 orders of magnitude. This makes cancer cells new
      cell 'species' with distinct, but unstable karyotypes, rather than mutant cells.
      The cancer-specific aneuploidies generate complex, malignant phenotypes, through
      the abnormal dosages of the thousands of genes, just as trisomy 21 generates Down
      syndrome. Thus cancer is a chromosomal rather than a genetic disease. The
      chromosomal theory explains (1) nonheritability of cancer, because aneuploidy is
      not heritable; (2) long 'neoplastic latencies' by the low probability of evolving
      competitive new species; (3) nonselective phenotypes via genes hitchhiking on
      selective chromosomes, and (4) 'immortality', because chromosomal variations
      neutralize negative mutations and adapt to inhibitory conditions much faster than
      conventional mutation. Based on this article a similar one, entitled 'The
      chromosomal basis of cancer', has since been published by us in Cellular Oncology
      2005;27:293-318.

PMID- 16627958
TI  - Adult stem cell theory of the multi-stage, multi-mechanism theory of
      carcinogenesis: role of inflammation on the promotion of initiated stem cells.
AB  - Inflammation, induced by microbial agents, radiation, endogenous or exogenous
      chemicals, has been associated with chronic diseases, including cancer. Since
      carcinogenesis has been characterized as consisting of the 'initiation',
      'promotion' and 'progression' phases, the inflammatory process could affect any
      or all three phases. The stem cell theory of carcinogenesis has been given a
      revival, in that isolated human adult stem cells have been isolated and shown to
      be 'targets' for neoplastic transformation. Oct4, a transcription factor, has
      been associated with adult stem cells, as well as their immortalized and
      tumorigenic derivatives, but not with the normal differentiated daughters. These
      data are consistent with the stem cell theory of carcinogenesis. In addition, Gap
      Junctional Intercellular Communication (GJIC) seems to play a major role in cell
      growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems
      to be the mechanism for the tumor promotion and progression phases of
      carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous
      inflammatory factors have been shown to inhibit GJIC and act as tumor promoters.
      The inhibition of GJIC might be the mechanism by which the inflammatory process
      affects cancer and that to intervene during tumor promotion with anti
      inflammatory factors might be the most efficacious anti-cancer strategy.

PMID- 16627959
TI  - Helicobacter pylori and gastric neoplasia.
AB  - Helicobacter pylori is present in the stomach of more than half of the world
      population. Based on compelling epidemiological evidences, it was classified by
      the World Health Organization as a type I gastric carcinogen. It is generally
      believed that gastric cancer development is a multi-step progression from chronic
      gastritis to atrophy, intestinal metaplasia, dysplasia, and cancer. Individuals
      infected with H. pylori have at least a 2-fold increase in risk of gastric cancer
      development though only a small proportion of infected individuals will
      ultimately develop this malignancy. The exact mechanisms underlying how H. pylori
      triggers or causes gastric cancer remain elusive. Certain H. pylori genotypes
      like cagA, vacA s1 or babA1 are considered to be of higher virulent potential.
      Apart from the bacterial factors, the host response to chronic H. pylori
      infection may also attribute to the cancer risk. It was found that individuals
      who carry pro-inflammatory cytokine gene polymorphism have a substantial increase
      in risk of cancer development. The combination of bacterial and host genotypes
      may have a synergistic effect on cancer development. Despite the strong causal
      link between chronic H. pylori infection and gastric cancer, the role of H.
      pylori eradication in preventing gastric cancer remains controversial. More long
      term data may be necessary to clarify this controversy.

PMID- 16627960
TI  - Schistosomiasis and neoplasia.
AB  - Schistosomiasis is endemic in at least 75 tropical and subtropical countries
      where 600 million people are at risk of which over 200 million are infected.
      Three species, S. hematobium, S. mansoni and S. japonicum, account for the
      majority of human infections. There is sufficient evidence that S. hematobium,
      the predominant etiologic agent for urinary schistosomiasis, is carcinogenic to
      humans leading to squamous cell carcinoma of the urinary bladder, a relatively
      uncommon vesical cancer in nonendemic areas. There is limited evidence suggesting
      that S. japonicum is possibly carcinogenic to humans leading to colorectal cancer
      and is a risk factor for hepatocellular carcinoma formation. There is inadequate
      evidence for the carcinogenicity of S. mansoni in humans. S. mansoni may still be
      linked to hepatocellular carcinoma through potentiating the effects of hepatitis
      B virus and hepatitis C virus on the liver. In this article, the relationship
      between schistosomiasis and neoplasia will be reviewed.

PMID- 16627961
TI  - Relevant oncogenic viruses in veterinary medicine: original pathogens and animal
      models for human disease.
AB  - Oncogenic viruses are important pathogens in farm and companion animals. These
      original pathogens are classified in various virus families, such as
      Retroviridae, Papillomaviridae, and Herpesviridae. Besides a role as pathogens
      for its original host, animal viruses serve as valuable models for viruses
      affecting humans, such as hepatitis B virus, and issues of immunity, therapy, but
      also basic pathophysiological mechanisms, can often only be addressed in those
      animal systems.

PMID- 16627962
TI  - The inflammatory tumor microenvironment and its impact on cancer development.
AB  - The role of the immune system during cancer development is complex involving
      extensive reciprocal interactions between genetically altered cells, adaptive and
      innate immune cells, their soluble mediators and structural components present in
      the neoplastic microenvironment. Each stage of cancer development is regulated
      uniquely by the immune system; whereas full activation of adaptive immune cells
      at the tumor stage may result in eradication of malignant cells, chronic
      activation of innate immune cells at sites of premalignant growth may actually
      enhance tumor development. In addition, the balance between desirable antitumor
      immune responses and undesirable pro-tumor chronic inflammatory responses largely
      depends on the context in which a malignancy is developing. The following chapter
      focuses on the inflammatory components and processes engaged during cancer
      development and the impact of the inflammatory microenvironment.

PMID- 16627963
TI  - Co-opting macrophage traits in cancer progression: a consequence of tumor cell
      fusion?
AB  - Tumor-associated macrophages (TAMs) play multiple roles in tumor initiation and
      progression. Tumors frequently appear in areas of chronic inflammation. This is
      likely aided by the mutagenic actions of macrophages. Tumor growth and
      progression is supported by macrophage-induced neoangiogenesis and stroma
      production, and macrophages produce tumor-stimulating growth factors. In most
      cancers a high density of TAMs predicts poor outcome. But not only do cancer
      cells depend upon macrophages for growth and invasion, they also co-opt
      macrophage traits. These include a wide diversity of molecules and pathways
      regulating adhesion, matrix alterations, neoangiogenesis, motility, chemotaxis,
      immune signaling pathways and even multidrug resistance proteins. Evidence is
      presented that these traits could be generated through macrophage-tumor cell
      fusion. Fusion has been reported in numerous animal tumor models and was recently
      documented in 2 human cases. Fusion could also account for the high degree of
      aneuploidy and plasticity in cancer, and for immune evasion. One common trait of
      myeloid-tumor fusion is the high expression of Beta1,6-branched N-glycans, used
      by macrophages in systemic migration. Beta1,6-branched oligosaccharides have long
      been associated with metastasis in animal models and were recently found to be
      common in a wide diversity of human cancers. We suggest that Beta1,6-branched
      oligosaccharides in human cancer may reflect widespread tumor cell fusion.
      Viewing the cancer cell as a myeloid hybrid provides new approaches towards
      understanding and treating this complex disease.

PMID- 16627964
TI  - Carcinogenesis driven by bone marrow-derived stem cells.
AB  - The overall mechanism of bone marrow-derived stem cell (BMDC) trans
      differentiation seems to be simple: BMDCs trans-differentiate as referred to the
      blueprint, which is given by the tissue itself. Thereby, the blueprint can be the
      local tissue micro-environment (defined by the tissue-specific cytokine,
      chemokine, adhesion molecule pattern, etc.), it can be a single cell (cell
      fusion), or it can be a combination of both. In fact stem cell trans
      differentiation is a complex not yet fully understood process. In between the
      start- and stop-points of transdifferentiation several gene reprogramming steps
      have to occur in a sequential step-by-step manner, for which a defined set of
      instructions is a prerequisite to ensure an accurate transdifferentiation.
      However, a recent study indicated that the ability of BMDCs - to adopt tissue
      function by reading its blueprint - seems to be a double-edged sword since BMDCs
      that have received a faulty blueprint, provided by chronically inflamed tissue,
      trans-differentiated into a neoplastic phenoytpe. Here, we review the importance
      of an accurate blueprint for BMDC trans-differentiation and discuss a model
      showing that BMDCs might contribute to overall tumor development due to
      recruitment to tumor tissue.

PMID- 16627965
TI  - Chemokine-directed metastasis.
AB  - Over the last 20 years, the biology of chemokines has expanded beyond their
      initial role in mediating migration of specific subsets of leukocytes. Chemokines
      have been found to display pleiotropic effects for enhancing immunity to tumor
      associated antigens, regulating angiogenesis, promoting proliferation/anti
      apoptosis of tumor cells; and mediating tumor cell invasion and trafficking in an
      organ-specific manner that leads to metastases. Here, we review the importance of
      chemokines, especially CXC chemokines in regulating angiogenesis, tumor cell
      invasion and metastases; and demonstrate why they can be seen as important
      therapeutic targets for intervention in cancer.

PMID- 16627966
TI  - Involvement of chemokine receptors in organ-specific metastasis.
AB  - The chemokines are a family of small proteins known for their ability to control
      cell migration in the body. Their receptors belong to the class A subfamily of G
      protein-coupled receptors. In recent years, chemokines have grown in importance,
      because they are involved in inflammation and autoimmune disease. Some of them
      are also involved in infectious disease, since two chemokine receptors, CXCR4 and
      CCR5, are used by the human immunodeficiency virus (HIV) to gain entry to cells.
      Several years ago it also became clear that chemokines can also influence tumor
      cells. Specifically, tumor cells express chemokine receptors in a nonrandom
      manner, and this suggested a role for chemokines in the metastatic destination of
      tumor cells. By far the most common chemokine receptor expressed by many cancer
      cells is CXCR4. Its ligand, CXCL12, is strongly expressed in lung, liver, bone
      marrow and lymph nodes, places that represent common metastatic destinations in
      many cancers. Many studies have now validated the concept that chemokines and
      their receptors influence metastasis. The potential therapeutic importance of
      these observations depends on the role that each metastatic destination such as
      liver, lung, bone marrow, etc., plays in the prognosis of a cancer patient.

PMID- 16627967
TI  - Visualization of tumor cell extravasation.
AB  - In cancer the blood-borne spread of tumor cells leads to the formation of
      secondary tumors at distant loci, whereby the extravasation of tumor cells is a
      prerequisite step during hematogenous metastasis. In regard to the fate of
      endothelial cells located at the site of tumor cell infiltration, tumor cell
      endothelial interactions were analyzed using an in vitro real-time model. This
      model shows the complete sequence of the transmigration process and gave new
      insights into the complex and dynamic cell-cell and cell-matrix interactions
      which occur during tumor cell transmigration across the endothelial barrier. An
      in vitro real-time apoptosis assay permits the distinction between apoptotic cell
      death from necrotic cell death. This model indicates that transmigration of tumor
      cell clusters derived from the invasive human bladder carcinoma cell line T24
      irreversibly damages the endothelial cells by inducing apoptosis at the site of
      tumor cell infiltration. It is postulated here that apoptosis induction
      facilitates the removal of detached endothelial cells, thereby forestalling a
      local inflammatory response which might be detrimental to extravasating tumor
      cells.

PMID- 16627968
TI  - Options for visualizing metastatic disease in the living body.
AB  - Detection and observation of primary tumor growth and metastasis in living
      subjects is an important task in clinical and basic cancer research. Recently
      several approaches and techniques emerged which offer a huge variety of options
      with respect to the specific objectives and questions of a given study. Recent
      developments in the field of in vivo imaging not only allow the assessment of
      anatomic information but also functional processes with cellular resolution and
      molecular sensitivity. This chapter will provide an overview of the most common
      imaging techniques which are currently available for the detection and
      observation of metastasizing tumor cells. General capacities, advantages,
      limitations and drawbacks will be discussed. These techniques include computed
      tomography (CT), molecular resonance imaging (MRI), positron emission tomography
      (PET), single photon emission computed tomography (SPECT), fluorescence imaging
      (FI), and bioluminescent imaging (BLI). The objective is to provide the cancer
      researcher with information that will help solve the dilemma of how best to apply
      the latest imaging tools for studying biological questions in the context of the
      living body.

PMID- 16627969
TI  - Infection, inflammation and neoplasia: an interdisciplinary challenge.
AB  - During the past two to three decades there has been an exciting revolution in our
      understanding of the multistage carcinogenic process and of the molecular
      genetics of cancer. The general principle of multifactor interactions is central
      to our understanding of cancer causation. The paradigm that persistent infections
      and chronic inflammation contributes via cytokine- and chemokine-mediated
      disbalanced immune response to carcinogenesis becomes more and more attractive in
      cancer research. Besides genetic factors, the epigenetics of impaired cell
      signaling and signal transduction by proinflammatory cytokines and chemokines are
      important potentiators of carcinogenesis. The activation of the nuclear factor
      kappaB, for example, a hallmark of inflammatory responses that is frequently
      detected in tumors, might constitute a missing link between inflammation and
      cancer. It will be a challenge for future therapeutic and preventive cancer
      research to detect potential targets in chronic inflammatory disease which are
      essential links to promote inflammation-associated cancer.

PMID- 16627971
TI  - Caveolin and STAT-5 signaling: potential overlap in lactation and breast tumor
      promotion.

PMID- 16627972
TI  - A potential role for resistant starch fermentation in modulating colonic
      bacterial metabolism and colon cancer risk.

PMID- 16627973
TI  - How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data,
      reflections and reactions.
AB  - RUNX3 is the oldest known gene in the RUNX family. Data have demonstrated its
      function to be thoroughly involved the neurogenesis of the dorsal root ganglia, T
      cell differentiation and tumorigenesis of gastric epithelium. As a TGF-beta
      target, RUNX3 protein is believed to be involved in TGF-beta-mediated tumor
      suppressor pathway; however, little is known about its role in apoptosis.
      According to recent data reported by Yamamura et al., (J Biol Chem 2006; 281:5267
      76), RUNX3 interacts with FoxO3a/FKHRL1 expressed in gastric cancer cells to
      activate Bim and induce apoptosis. The cooperation between RUNX3 and the PI3K/Akt
      signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in
      the homoeostasis of gastric cells and in stomach cancer control. Here we discuss
      recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric
      malignancy and comment on possible future trends and perspectives.

PMID- 16627974
TI  - Hypoxic microenvironment as a cradle for melanoma development and progression.
AB  - Hypoxia-inducible factor (HIF)-1alpha, a global regulator of oxygen homeostasis,
      plays a crucial role in tumor cell adaptation to the hypoxic microenvironment
      through transcriptional regulation of its target genes. These genes in turn are
      involved in a plethora of biochemical as well as cell biological processes,
      including glucose metabolism, apoptosis and angiogenesis. In melanoma, HIF-1alpha
      has been implicated in tumor progression with effects upon metastasis and
      angiogenesis. However, its role in malignant transformation by oncogenes has not
      been described. Bedogni et al. (Cancer Cell 2005, 8:443-54) report that the
      hypoxic microenvironment in the skin contributes to melanocyte transformation and
      tumor growth induced by oncogenes Ras and Akt, which are frequently activated in
      melanoma. HIF-1alpha activity was found to be required in Akt-induced melanocyte
      transformation and tumor growth and it was suppressed greatly by mTOR inhibition
      with rapamycin. Since mTOR regulates HIF-1alpha expression and its
      transcriptional activity, rapamycin was proposed as a promising hypoxia-related
      therapeutic approach in melanoma treatment. This study sheds light upon the role
      of HIF-1alpha in the early stage of melanoma development and highlights the
      importance of the Akt-mTOR pathway in the regulation of HIF-1alpha.

PMID- 16627975
TI  - Chemosensitizing multiple drug resistance of human carcinoma by Bicyclol involves
      attenuated p-glycoprotein, GST-P and Bcl-2.
AB  - Bicyclol, a second generation of synthetic hepatoprotectant being used in China
      for anti-hepatitis therapy, shows chemosensitizing effect on reverting multiple
      drug resistance (MDR) of cytostatic agents in two established MDR carcinoma cell
      lines, vincristine resistant human stomatic epidermoid carcinoma VinRKB and
      adriamycin resistant human breast carcinoma AdrRMCF-7. The reversal rate of drug
      resistance was calculated from the changes of the IC50 of cell growth inhibition.
      Bicyclol at the concentration of 25, 50, 100 microM induced 2.8 7.3 and 20.7
      fold, respectively, reversal of vincristine resistance in VinRKB cell. Bicyclol
      also reversed the cross-resistance of VinRKB cell to taxol and AdrRMCF-7 cell
      resistance to adriamycin at the similar range of potency. Further, Bicyclol
      recovered the reduced accumulation of adriamycin in AdrRMCF-7 cell partially to
      the level in drug-sensitive MCF-7 cell, indicate the inhibition of MDR related
      membrane efflux pump system. Overexpression of membrane p-glycoprotein coded by
      Mdr-1 genes, the most common efflux pump correlated to MDR, was found in both
      VinRKB and AdrRMCF-7 cells by Western blot and immunocytochemistry as compared
      with drug-sensitive cells. The p-glycoprotein was decreased to the levels in drug
      sensitive cells when VinRKB and AdrRMCF-7 cells were treated with Bicyclol for 12
      72 hours. Both VinRKB and AdrRMCF-7 cells showed increased GSH contents, and
      AdrRMCF-7 cell showed increased GST activity and the overexpression of Bcl-2
      protein, by which molecules are tightly related to the MDR formation besides Mdr
      1 p-glycoprotein. Bicyclol reduced the GSH contents, GST activities and Bcl-2
      expression. All these data demonstrate that, by modifying the expressions of Mdr
      1, GSH/GST and Bcl-2, Bicyclol increases the intracellular drug concentration and
      sensitizes the resistant cells to the anti-carcinoma agents.

PMID- 16627976
TI  - Selenomethionine induces p53 mediated cell cycle arrest and apoptosis in human
      colon cancer cells.
AB  - While there is an increasing interest in selenium chemoprevention against human
      colon polyp recurrence and other cancers, the mechanism(s) by which these agents
      inhibit carcinogenesis are uncertain. Some of the proposed mechanisms include the
      inhibition of cytosine methyltransferases, carcinogen bioactivation, and
      inhibition of cyclooxygenase (COX). More recently, it has been suggested that
      selenium may exert growth inhibitory effects by activating p53. However, the
      molecular mechanisms of action of selenomethionine, an organoselenium compound
      present in selenized yeast and currently being investigated in human clinical
      trials for colon polyp prevention, are unclear. In the present study we tested
      the hypothesis that selenomethionine might affect colon cancer cell growth by p53
      mediated apoptosis and/or cell cycle regulation. Four human colon cancer cell
      lines including HCT116 and RKO (wild type p53), HCT116-p53KO (isogenic control of
      HCT116 cells with p53 knocked out) and Caco-2 (mutant p53) were treated with 0
      100 microM of selenomethionine for 24, 48 and 72 h. Cell viability rates were
      determined by the MTT assay. Cell cycle analysis was performed by flow cytometry
      and apoptosis measured by Annexin V-Cy5 staining. Expression of p53 protein was
      determined by Western blotting and immunofluorescence assays. All cell lines
      showed concentration and time dependent growth inhibition with selenomethionine,
      although HCT116 and RKO cells were the most sensitive to such treatments.
      Interestingly, although HCT116 and HCT116-p53KO are isogenic cell lines,
      selenomethionine caused a G2/M cell cycle arrest in HCT116 and RKO cells, but not
      in HCT116-p53KO cells. Similarly, both HCT116 and RKO demonstrated a significant
      increase in apoptosis (100-170%; p < 0.01) with 50-100 microM selenomethionine.
      Cell cycle arrest and apoptosis observed in HCT116 and RKO cell lines were
      accompanied by a marked increase in p53 protein expression following selenium
      treatment. These results clearly suggest that selenomethionine exerts p53
      dependent growth inhibitory effects in colon cancer cells by inducing G2/M cell
      cycle arrest as well as apoptosis.

PMID- 16627977
TI  - Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G
      heterozygosity of the QM gene are associated with ovarian cancer.
AB  - The QM gene is located at Xq28 of the X chromosome. QM may act as a tumor
      suppressor and may also participate in the 60S ribosomal subunit assembly. We
      studied loss of heterozygosity (LOH) and microsatellite instability (MSI) of
      microsatellite markers DXS15A, DXS1107, WI12360 and WI9327 for the Xq28 region in
      29 ovarian cancer biopsies. The results showed that the LOH frequencies were
      18.2%, 30%, 26.3% and 20.8% for WI12360, WI9327, DXS1107 and DXS15A,
      respectively, whereas the MSI rates were 18.2%, 50.0%, 31.6% and 12.5%,
      respectively. All tumors showed LOH or MSI for at least one of these markers.
      Sequencing the QM cDNA did not identify any mutation other than the adenine
      (A)/guanine (G) replacement at the 605th nucleotide which changes the coding from
      serine to asparagine. In 17 (58.6%) of the 29 tumors, both A and G types of QM
      mRNA were detected, indicating that the QM was A/G heterozygous and escaped X
      inactivation. However, cDNA and genomic DNA sequencing revealed that the adjacent
      normal tissues showed the A/G heterozygosity in only 3 of the 17 cases, while in
      the remaining 14 cases, four had no more adjacent tissue available and ten
      revealed either G or A at the 605th nt, indicating an A/G point mutation in these
      tumors. The allele distribution was 32.8% for the A and 67.2% for the G type QM
      gene. The frequencies of A/A, G/G and A/G homo- or hetero-zygosity were 3.5%,
      37.9% and 58.6%, respectively in cancer tissues but they were 26.1%, 52.2% and
      21.7%, respectively in the adjacent tissues, indicating a higher heterozygous
      rate in cancer (58.6% vs 21.7%, p < 0.01). These results suggest that high
      frequencies of LOH and MSI at the Xq28 and of the A/G heterozygosity at the 605th
      nt of the QM gene may be associated with ovarian cancer.

PMID- 16627978
TI  - Proteomic analysis of hemangioblastoma cyst fluid.
AB  - OBJECTIVE: Hemangioblastomas are benign CNS tumors that occur sporadically or in
      patients with von Hippel-Lindau (VHL) disease. These tumors are
      characteristically associated with formation of intra- or peritumoral cysts.
      Hemangioblastoma cyst formation is a major cause of morbidity and mortality with
      these tumors. While peritumoral cysts have been suggested to result from vascular
      leakage, the mechanism of intratumoral cyst formation is not understood. METHODS:
      To elucidate the origin of intratumoral hemangioblastoma cyst fluid, we
      characterized its biochemical composition by two-dimensional (2D) proteomic
      profiling followed by sequencing of several proteins. The proteomic pattern of
      intratumoral cyst fluid was furthermore compared to the proteomic pattern of
      serum, hemangioblastoma tumor tissue, and hemangioblastoma peritumoral cyst
      fluid. RESULTS: We show that proteomic patterns of intra- and peritumoral cyst
      fluid are identical Both are highly similar to serum and not to tumor.
      CONCLUSIONS: Intratumoral hemangioblastoma cyst fluid originates from serum. Cyst
      formation associated with hemangioblastoma, whether peri- or intratumoral, is a
      consequence of vascular leakage. Anti-VEGF therapy may effectively control
      hemangioblastoma cyst formation.

PMID- 16627979
TI  - Coexpression of erythopoietin and erythopoietin receptor in sporadic clear cell
      renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (CCRCC) is the most common renal carcinoma and it
      is often associated with von Hippel-Lindau disease (VHL) gene mutations. CCRCCs
      with VHL mutations demonstrate hypoxia-inducible factor (HIF) overexpression as
      well as increased expression of vascular endothelial growth factor (VEGF).
      Recently, the erythropoietin (Epo) has been found to be upregulated in renal and
      other tumors associated with VHL disease. Furthermore, Epo and Epo receptor
      (EpoR) coexpression has also been reported in these tumors. The results provided
      strong evidence that an autocrine loop is involved in tumorigenesis in VHL
      disease. We investigated whether Epo and EpoR coexpression also occurs in
      sporadic CCRCC. Fifty-four sporadic CCRCCs were analyzed. VHL gene mutations were
      detected in 30 out of 54 tumors. Coexpression of Epo and EpoR was detected in 50
      out of 54 tumors regardless of their VHL mutation status. The results suggest
      that coexpression of Epo and EpoR plays an important role in tumorigenesis of
      sporadic CCRCC.

PMID- 16627980
TI  - Annexin-1 downregulation in thyroid cancer correlates to the degree of tumor
      differentiation.
AB  - We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell
      lines and in thyroid cancers with a different degree of differentiation. The
      highest level of ANXA1 expression examined by Western blotting was detected in
      the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the
      other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO)
      presented the lowest level of ANXA1 expression. In surgical tissue specimens from
      32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in
      papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated
      thyroid cancers (UTC) the expression of the protein was barely detectable.
      Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC
      examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested
      showed high expression of the protein. Thus ANXA1 expression may correlate with
      the tumorigenesis suggesting that the protein may represent an effective
      differentiation marker in thyroid cancer.

PMID- 16627981
TI  - Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by
      suppression of NF-kappaB survival signaling in hepatocellular carcinoma.
AB  - CYLD is a tumor suppressor gene related to cylindroma and is negative regulator
      of NF-kappaB. However, antitumor effect of CYLD has not been reported. The
      activation of NF-kappaB induced by tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) renders hepatocellular carcinoma (HCC) resistant to TRAIL
      mediated cell apoptosis. Here we described that the adenoviral vector expressing
      CYLD (Ad/hTERT-CYLD) augmented the cytotoxicity of TRAIL in HCC cells by
      negatively regulating NF-kappaB activity since CYLD could reverse the
      ubiquitination of TNF receptor-associated factor 2 (TRAF2) and interact with the
      IkappaB kinasegamma (IKKgamma). The combined treatment of Ad/hTERT-CYLD and a
      conditionally replicating adenovirus carrying TRAIL gene (ZD55-TRAIL) induced
      rapid and potent apoptosis in HCC cells, characterized by activation of caspase
      3, caspase-8, PARP and the reduction of X-linked inhibitor of apoptosis protein
      (XIAP). In animal study, the combined treatment could eradicate the BEL7404
      xenograft tumors. In contrast, treatment with Ad/hTERT-CYLD or ZD55-TRAIL alone
      achieved less antitumor effect. IN CONCLUSION: CYLD inhibits TRAIL-mediated NF
      kappaB activation and enhances the sensitivity of HCC cells to TRAIL-triggered
      apoptosis. The combined delivery of Ad/hTERT-CYLD and ZD55-TRAIL may be a new
      useful strategy for HCC or other tumor cells with enhanced NF-kappaB activity.

PMID- 16627982
TI  - Homozygous deletion of MKK4 in ovarian serous carcinoma.
AB  - Analysis of deleted chromosomal regions in tumors has historically led to the
      identification of tumor suppressor genes. In this study, we used digital
      karyotyping, a genome-wide, high-resolution technology, to search for chromosomal
      deletions in ovarian serous carcinoma, the most lethal gynecological malignancy
      in women. Five purified ovarian serous carcinomas were analyzed by digital
      karyotyping and small interstitial deletions at chromosome 17p were identified in
      two tumor samples. Aligning these two deletions identified an overlapping region
      that spanned 2.4 Mb which harbored a candidate tumor suppressor gene, mitogen
      activated protein kinase kinase-4 (MKK4). Dual-color FISH analysis confirmed
      homozygous deletion of the MKK4 locus in both samples and RT-PCR demonstrated
      that both carcinomas lacked MKK4 transcript expression. Loss of heterozygosity of
      17p occurred in 24 (86%) of 28 high-grade serous carcinomas including both cases
      with homozygous MKK4 deletion. Additionally, downregulation of MKK4 expression
      was found in 96 (75%) of 128 ovarian serous carcinomas as compared to benign
      ovarian tissues. These findings suggest that homozygous deletion or reduced
      expression of MKK4 may contribute to the development of ovarian serous carcinoma.

PMID- 16627983
TI  - Inhibition of CD147 expression reduces tumor cell invasion in human prostate
      cancer cell line via RNA interference.
AB  - CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), has
      been proved to be involved in the invasion and metastasis processes of tumor
      cells in many types of cancers. To determine the role of CD147 in the
      invasiveness properties of prostate cancer, we successfully downregulated CD147
      by RNA interference (RNAi) technology, in PC-3 cell line at high level of CD147
      expression. PC-3 cells were transfected with a pSilencer 4.1-CMV neo Vector
      coding for an RNA composed of two identical 19-nucleotide sequence motifs in an
      inverted orientation, separated by a 9-bp spacer to form a hairpin dsRNA capable
      of mediating target CD147 inhibition. Gelatin zymography was employed to
      determine the effect on reducing secretions of MMP-2 and MMP-9 of the transfected
      cells. Matrigel invasion assay was performed to evaluate the invasion ability of
      PC-3 cells in vitro. Our results showed that CD147 expression was significantly
      inhibited by small interfering RNAs (siRNA) transfectants in PC-3 cells at mRNA
      and protein levels, which resulted in dramatic reduction of invasion ability in
      tumor cells. Moreover, downregulation of CD147 resulted in reducing secretions of
      MMP-2, MMP-9. Taken together, CD147 downregulation by RNAi technology decreases
      the invasive capability of prostate cancer cells, demonstrating that stable
      expression of siRNA CD147 could potentially be an experimental approach for
      prostate cancer gene therapy.

PMID- 16627984
TI  - Molecular markers of hepatitis C virus-related hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is triggered by many factors including infection
      with hepatitis C virus (HCV). However, the molecular basis of the development of
      HCV-related HCC remains unknown. The present study was designed to reveal the
      interference of the HCV infection in HCC patients with a set of anti-apoptotic
      factors, and expression levels of some molecular markers between HCV-related HCC
      and non-HCV-related HCC. We have determined the plasma circulating levels of Bcl
      2, TGF-betaI, VEGF, beta2-MG and immunohistochemistry staining of p53 in HCV
      related HCC patients (n = 40) and compared them in relation to both HCV-free HCC
      patients (n = 37) and normal control group (n = 20). The present data do not
      distinctly predict a significant role of HCV infection on the circulating Bcl-2
      protein since in both HCC and HCC/HCV groups a limited number of patients have
      high levels of Bcl-2. However, TGF-betaI expression is markedly decreased in all
      patients, particularly in HCC associated with HCV. Moreover, serum VEGF is
      significantly higher in HCC patients with or without HCV infection than in normal
      control. No significant difference, however, was found between HCV-infected and
      HCV-free groups. Presence of HCV is associated with a high incidence of Loss of
      Heterozygosity (LOH) at M6P/IGFIIr site compared to HCV-free patients. Although
      beta2-MG is markedly elevated in all patients, a significant increase was
      observed in the presence of HCV. Immunohistochemical positive total staining for
      p53 protein was detected in 32/77 (41.5%); HCC-positive HCV was 21/40 (52.2%),
      and HCC-negative HCV was 11/37 (29.73%). Collectively, in HCC patients, HCV
      infection does not affect the levels of Bcl-2 and VEGF. beta2-MG and LOH levels
      at the M6P/IGFIIr site were higher in the presence of HCV concomitant with a
      decrease in TGF-beta1. There was no significant correlation between p53 and stage
      of the disease or between p53 protein expression and clinicopathological
      manifestations.

PMID- 16627985
TI  - Oral ingestion of streptococcus thermophilus diminishes severity of small
      intestinal mucositis in methotrexate treated rats.
AB  - BACKGROUND: Currently, there are no available effective preventative or
      adjunctive agents to alleviate symptoms of chemotherapy-induced mucositis. This
      is compounded by the absence of a recognized and validated noninvasive biomarker
      to assess gut function. This study investigated the effects of orally ingested
      Streptococcus thermophilus (TH-4) on chemotherapy-induced small intestinal damage
      in rats using the noninvasive (13)C-sucrose breath test (SBT). METHODS:
      Gastrointestinal damage was induced in 27 female dark agouti rats (148 +/- 1g)
      with MTX (1.5 mg/kg; i.m.). Rats received MTX or saline at 0 h; with daily
      treatment of: TH-4 at doses of 10(9) (high), 10(8) (low) cfu/mL, or skim milk
      (vehicle), 48 h pre and 96 h post-MTX. The noninvasive (13)C-sucrose breath test
      (SBT) was conducted at -24, 24 and 96 h post-MTX to monitor gut function. At
      sacrifice, small intestinal tissues were collected for determinations of sucrase
      activity, myeloperoxidase (MPO) activity and histological assessment. RESULTS:
      MTX + vehicle and MTX + low TH-4-treated rats produced significantly lower SBT
      and sucrase activity results compared to saline controls (p < 0.001). In
      contrast, MTX + high TH-4 treatment showed no significant differences in the SBT
      compared to saline controls, and the SBT results were significantly higher
      compared to MTX + vehicle and MTX + low TH-4 (p < 0.05). MPO levels were
      significantly elevated (p < 0.05) in MTX + vehicle and MTX + low TH-4, but not
      following MTX + high TH-4 treatment, compared to saline controls. This was
      further confirmed by histological analyses. CONCLUSION: Oral ingestion of TH-4 at
      10(9) cfu/mL is capable of partially attenuating small bowel damage in rats. The
      noninvasive SBT is a useful technique to longitudinally assess the efficacy of
      treatments or interventions for small bowel disease.

PMID- 16627986
TI  - Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal
      carcinomas.
AB  - Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role
      in breast cancer development. Even though SMAD4 is located on 18q21, a region
      frequently lost in breast cancers, point mutations of SMAD4 were rarely observed,
      implying that biallelic inactivation of SMAD4 was not necessary in the process.
      In this study, a novel homozygous deletion of SMAD4 was identified in breast
      cancer cell line SW527 during a screening of 31 breast cancer cell lines. As
      several breast cancer cell lines were shown to contain SMAD4 homozygous deletion,
      we sought to develop a reliable method to access such lesions in archived primary
      tumor specimens. First, a DNA quantification method was developed to measure as
      few as 5 copies of DNA templates so that the amount of genomic DNA isolated by
      laser-capture microdissection can be accurately determined. Next, accurate DNA
      quantitation allowed sufficient DNA templates to be included in the homozygous
      deletion assay for the robust amplification of SMAD4 genetic markers. Two out of
      24 primary infiltrative ductal carcinomas (IDC) with 18q allelic imbalance were
      determined to contain SMAD4 homozygous deletions, and these samples are also
      negative for Smad4 protein expression by immunohistochemistry. Our data suggest
      that biallelic inactivation of SMAD4 through homozygous deletion does occur in a
      small percentage of IDCs, and support the hypothesis that inactivation of TGF
      beta/SMAD4 signaling plays in a role in the development of a subset of IDC.

PMID- 16627987
TI  - Use of immuno-LCM to identify the in situ expression profile of cellular
      constituents of the tumor microenvironment.
AB  - Expression profiling using microarrays has become an essential tool for
      interrogating tumor biology. However, profiling of whole tumor RNA reflects both
      tumor and host cells, making it difficult to dissect molecular events within
      specific cellular compartments in the tumor microenvironment. We developed and
      optimized a simple, rapid technique combining immunohistochemistry and laser
      capture microdissection (immuno-LCM) to purify specific cell populations from the
      tumor microenvironment followed by RNA isolation and amplification for microarray
      analysis. Using this methodology, we were able to elucidate the in situ
      expression profile of pure tumor cells and tumor endothelial cells from ovarian
      tumors with brisk immune infiltrates. This technique not only increased the
      specificity of profiling isolated cell populations, eliminating genes expressed
      by surrounding cells, but also increased the sensitivity of analysis, allowing
      for the detection of low expression genes that were not detected in whole tumor
      arrays. Pathway analysis of tumor cells in situ identified distinct activation of
      signaling pathways converging on NF-kappaB, as compared to pathways identified in
      cultured tumor cell lines, which were primarily metabolic. Profiling of tumor
      vascular cells revealed most known panendothelial and tumor endothelial-specific
      markers, and unveiled genes specific to the myeloid-monocytic lineage. We propose
      that immuno-LCM coupled with transcriptional profiling is a convenient tool for
      dissecting molecular and cellular events in complex biological systems such as
      the tumor microenvironment.

PMID- 16627988
TI  - Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain
      (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab.
AB  - The HER-2 receptor tyrosine kinase is an important regulator of cell
      proliferation and survival, and it is a clinically validated target of
      therapeutic intervention for HER-2 positive breast cancer patients. Its
      extracellular domain (ECD) is frequently cleaved by protease(s) in HER-2
      overexpressing breast cancer patients, rendering the remaining membrane-bound
      portion (p95) a constitutively activated kinase. The presence of both serum ECD
      and cellular p95 protein has been linked to poor clinical outcome as well as
      reduced effectiveness of some therapeutic treatments. We have identified a series
      of potent, selective small molecule inhibitors of ADAM proteases, exemplified
      here by INCB003619, and demonstrate that these inhibitors effectively block HER-2
      cleavage in HER-2 overexpressing human breast cancer cell lines. Intriguingly,
      when used in combination, INCB003619 dramatically enhances the antiproliferative
      activity of suboptimal doses of the anti-HER-2 antibody, trastuzumab, in HER-2
      overexpressing/shedding breast cancer cell lines, accompanied by reduced ERK and
      AKT phosphorylation. Furthermore, INCB003619, in combination with trastuzumab,
      augments the pro-apoptotic and antiproliferative effects of the chemotherapeutic
      agent paclitaxel. Consistent with these in vitro data, INCB003619 reduces serum
      ECD levels and enhances the antitumor effect of trastuzumab in a xenograft tumor
      model derived from the HER-2 overexpressing BT-474 breast cancer cell line.
      Collectively, these findings suggest that blocking HER-2 cleavage with selective
      ADAM inhibitors may represent a novel therapeutic approach for treating HER-2
      overexpressing breast cancer patients.

PMID- 16627989
TI  - Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity
      in HER2 overexpressing breast cancer cells.
AB  - Overexpression and activating mutations of ErbB family members have been
      implicated in the development and progression of a variety of tumor types.
      Cleavage of the HER2 receptor by an as yet unidentified ectodomain sheddase has
      been shown to liberate the HER2 extracellular domain (ECD) leaving a fragment
      with constitutive kinase activity that can provide ligand-independent growth and
      survival signals to the cell. This process is clinically relevant since HER2 ECD
      serum levels in metastatic breast cancer patients are associated with a poorer
      prognosis. Thus, inhibition of the HER2 sheddase may provide a novel therapeutic
      approach for breast cancer. We describe the use of transcriptional profiling,
      pharmacological and in vitro approaches to identify the major source of HER2
      sheddase activity. Real-time PCR was used to identify those ADAM family members
      which were expressed in HER2 shedding cell lines. siRNAs that selectively
      inhibited ADAM10 expression reduced HER2 shedding. In addition, we profiled over
      1000 small molecules for in vitro inhibition of a panel of ADAM and MMP proteins;
      a positive correlation was observed only between ADAM10 inhibition and reduction
      of HER2 ECD shedding in a cell based assay. Finally, in vitro studies demonstrate
      that in combination with low doses of Herceptin, selective ADAM10 inhibitors
      decrease proliferation in HER2 overexpressing cell lines while inhibitors, that
      do not inhibit ADAM10, have no impact. These results are consistent with ADAM10
      being a major determinant of HER2 shedding, the inhibition of which, may provide
      a novel therapeutic approach for treating a variety of cancers with active HER2
      signaling.

PMID- 16627990
TI  - Human tumor mutants in the p110alpha subunit of PI3K.
AB  - The PI3K-Akt pathway is frequently upregulated in human tumors. Recently, somatic
      mutations of PIK3CA, encoding p110alpha catalytic subunit of Class IA PI3Ks, have
      been found in various cancers. The two most common types of p110alpha mutants,
      those in the helical and kinase domains, have been shown to be very potent in Akt
      activation and oncogenic transformation by several groups. Notably these common
      mutations may not enhance recruitment of p110alpha to the plasma membrane where
      its substrates are located. We have investigated the effect of membrane
      localization on common PIK3CA tumor mutants via myristoylation. In addition we
      have studied a third class of less frequent mutants in the p85-binding domain, in
      an attempt to gain insight into p85's inhibitory effect on p110alpha. This
      article briefly reviews and extends the literature on mutant forms of p110alpha.

PMID- 16627991
TI  - Regulation of p14ARF through subnuclear compartmentalization.
AB  - The p53-mediated pathway cell cycle arrest and apoptosis is central to cancer and
      an important point of focus for therapeutics development. The p14ARF ("ARF")
      tumor suppressor induces the p53 pathway in response to oncogene activation or
      DNA damage. However, ARF is predominantly nucleolar in localization and engages
      in several interactions with nucleolar proteins, whereas p53 is nucleoplasmic.
      This raises the question as to how ARF initiates its involvement in the p53
      pathway. We have found that UV irradiation of cells disrupts the interaction of
      ARF with two of its nucleolar binding partners, B23 (NPM, nucleophosmin, NO38,
      numatrin) and topoisomerase I, and promotes an immediate and transient subnuclear
      redistribution of ARF to the nucleoplasm, where it can engage the p53 pathway
      (Lee et al, Cancer Res 65:9834-42; 2005). The results support a model in which
      the nucleolus serves as a p53 upstream sensor of cellular stress, and add to a
      growing body of evidence that nucleolar sequestration of ARF prevents activation
      of p53. The results also have therapeutic implications for therapies based on
      exploiting p53 and other cellular stress response pathways to suppress cancer.

PMID- 16627992
TI  - Single cell FRET imaging for determination of pathway of tumor cell apoptosis
      induced by photofrin-PDT.
AB  - Apoptosis is an important cellular event that plays a key role in pathogeny and
      therapy of many diseases. Apoptosis has been associated with photodynamic therapy
      (PDT) and its pathway is important in the mechanistic study of PDT. We show that
      single cell fluorescent imaging can be used to determine the pathway of PDT
      induced tumor cell apoptosis. In this study, ASTC-a-1 tumor cells transfected by
      plasmid DNA SCAT3 were treated by Photofrin-PDT. The intracellular distribution
      of Photofrin was observed using a confocal microscope. The activations of caspase
      3 and caspase-8 were dynamically observed using fluorescence resonance energy
      transfer (FRET). Our experimental results show that the Photofrin molecules are
      localized in cell mitochondria, and that after PDT caspase-3 was activated
      rapidly while caspase-8 remained inactive. These results demonstrate that the
      tumor cell apoptosis induced by Photofrin-PDT was directly initiated from the
      mitochondrial pathway.

PMID- 16627993
TI  - The HIRAN domain and recruitment of chromatin remodeling and repair activities to
      damaged DNA.
AB  - Aided by sensitive sequence profile searches we identify a novel conserved domain
      in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p
      (hence HIP116, Rad5p N-terminal domain: HIRAN domain). We show that the HIRAN
      domain is found as a standalone protein in several bacteria and prophages, or
      fused to other catalytic domains, such as a nuclease of the restriction
      endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. Based on
      a network of contextual connections in the form of domain architectures,
      conserved gene neighborhoods and functional interactions we predict that the
      HIRAN domain is likely to function as a DNA-binding domain that probably
      recognizes features associated with damaged DNA or stalled replication forks. It
      might thus act as a sensor to initiate a damaged DNA checkpoint and engage
      different DNA repair and chromatin remodeling or modifying activities to these
      sites. In evolutionary terms, the fusion of the HIRAN domain, and the
      functionally analogous RAD18 Zn-finger and the PARP-type Zn-finger to SWI2/SNF2
      ATPases appears to have been a notable factor for recruiting these ATPases for
      chromatin modification and remodeling in the context of DNA repair.

PMID- 16627994
TI  - MicroRNA control of lifespan and metabolism.
AB  - A family of small, noncoding RNAs, known as microRNAs, has recently emerged as
      sequence-specific regulators of gene expression. Hundreds of microRNAs have been
      identified in almost all metazoans genomes, but they are only beginning to be
      classified by functional roles. Here, we review microRNAs that have been shown to
      play roles in two closely related processes, lifespan and metabolic regulation.
      Understanding the metabolic and lifespan regulatory roles of these novel gene
      regulators will undoubtedly further our understanding of the complex genetic
      networks that control lifespan and metabolism, and will also provide us with
      novel targets for the therapeutic intervention of metabolic and age-related
      diseases.

PMID- 16627995
TI  - p38 MAPK in development and cancer.
AB  - p38 is a MAPK that has been shown to induce a wide variety of biological effects
      in cell culture in response to a wide range of stimuli. These effects are
      dependent not only on the stimuli, but also on the cellular context, resulting in
      a bewildering array of possibilities. For example, p38 was shown to induce
      apoptosis in some cells, but prevent apoptosis in others. Similarly opposed
      effects had been observed with respect to cell cycle regulation. The role of p38
      in inflammatory disease has been appreciated from the beginning, since it was
      initially identified as an cytokine inducer. More recently, p38 function has been
      evaluated in vivo, and through these studies p38 has emerged as an important
      regulator of both embryonic development and cancer progression. This review will
      focus on these in vivo studies in an effort to provide perspective on p38
      biologically and as a pharmacological target.

PMID- 16627996
TI  - Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide?
AB  - The formation of distant metastases is the deadliest phase of cancer progression.
      Although numerous studies have identified genes and mechanisms that affect
      metastasis after tumors have reached secondary sites, our knowledge about how
      cancer cells initially gain access to systemic circulation is limited. Since
      tumors can enter the blood directly by intravasating into venous capillaries or
      indirectly via lymphatics, it is important to evaluate the relative contributions
      of both pathways as routes of egress from the primary site. Insights into tumor
      and stromal factors governing the intravasation process may help explain why
      certain tumors exhibit "preferred" pathways for metastatic dissemination, both
      clinically and in experimental animal models.

PMID- 16627997
TI  - Polo-like kinases: a team in control of the division.
AB  - Polo, the founding member of the family of polo-like kinases (Plks) was
      identified in a Drosophila screen for mutants affecting spindle pole behavior.(1)
      Several mutants showed defects at their spindle poles and were hence named after
      the magnetic poles of the earth or geo-magnetic phenomena associated with them,
      like Polo and Aurora. Currently, the conserved family of Plks consists of many
      members throughout various species. Multiple Plks are present in mammalian cells
      (Plk1, Plk2/Snk, Plk3/Fnk/Prk, and Plk4/Sak) and Xenopus (Plx1-3), whereas in
      other species only one member has been identified, like Polo in Drosophila, Cdc5
      in budding yeast and Plo1 in fission yeast. Plks are now viewed as important
      regulators of multiple functions before and during the mitotic cell division. In
      this review, we will focus our attention on human Plk1 and its family members
      Plk2-4 and the many roles they play during mitosis. Furthermore, we will describe
      the currently knowledge of the regulation of these functions.

PMID- 16627998
TI  - Check, double check: the G2 barrier to cancer.
AB  - Loss of the G1/S checkpoint is recognized as a mandatory step in the development
      of cancer. Nevertheless, both in vivo and in vitro experiments have indicated
      that this condition highly sensitizes cells to apoptosis, e.g., primary mouse
      embryonic fibroblasts that lack the complete retinoblastoma suppressor gene
      family (TKO MEFs) massively die under mitogen-deprived conditions. The prevailing
      hypothesis therefore is that the increased proliferative capacity of cells that
      have lost the G1/S checkpoint becomes apparent by suppression of apoptosis.
      However, this view was recently challenged by the finding that suppression of
      apoptotic cell death in TKO MEFs did not allow unconstrained proliferation;
      instead, cells became arrested in G2. This mechanism, which is dependent on p53,
      provides yet another barrier to oncogenic transformation. Thus, progression to
      malignancy of Rb-deficient lesions by alleviation of G2 arrest may offer an
      alternative explanation for the synergism between loss of Rb and p53 in
      tumorigenesis.

PMID- 16627999
TI  - The fission yeast APC activator Ste9 is regulated by mRNA decay.
AB  - Fission yeast Ste9/Srw1 is a family member of the Fizzy-related APC activators
      that promote the ubiquitination and degradation of mitotic cyclins and other
      substrates at the end of mitosis and G1. These proteins are highly regulated
      during the cell cycle at the level of gene transcription and protein
      phosphorylation in order to guarantee the correct order of events during the cell
      cycle. Here we propose mRNA decay as a novel mechanism that regulates ste9+ gene
      expression during the cell cycle. We have characterized the elements in the 3'UTR
      of the ste9 mRNA responsible for this mechanism. Moreover, we demonstrate that
      the instability of ste9 mRNA is important for downregulating Ste9 levels in G2,
      allowing appropriate cyclin B accumulation to promote timely entry into mitosis.

PMID- 16628000
TI  - Chromosomal instability, colorectal cancer and taxane resistance.
AB  - The spindle checkpoint monitors the fidelity of chromosome separation during
      mitosis. Aberrations in key regulators of this process have been found in human
      malignancies associated with chromosomal instability (CIN). Important
      chemotherapeutic agents which alter microtubule dynamics such as paclitaxel and
      vincristine, prolong spindle checkpoint activation and delay the completion of
      mitosis. Intriguingly, inhibition of BubR1 or overexpression of Aurora kinase A,
      spindle checkpoint regulators implicated in CIN, promote resistance to
      microtubule inhibitors (MTIs) in vitro. Taxanes have failed to demonstrate
      significant clinical benefit in phase II trials in colorectal cancer (CRC). The
      high incidence of CIN in this disease, coupled with alterations in spindle
      checkpoint regulators in vivo, may explain the disappointing results associated
      with taxane based therapies for CRC. A phase II trial of taxanes in patients with
      metastatic CIN negative CRC may be indicated.

PMID- 16628001
TI  - p8 and prothymosin alpha: unity is strength.
AB  - p8 and prothymosin alpha are two natively unstructured proteins with anti
      apoptotic activity. We showed that their interaction results in the formation of
      a one-to-one heterodimer complex with stable structure. To test whether the
      heterodimer bears the function previously attributed to both proteins, we
      monitored the consequences on apoptosis of modulating in vitro the concentrations
      of both proteins. Overexpression was obtained by transfection of appropriate
      vectors and inhibition by using specific siRNAs. In all conditions inhibition of
      apoptosis correlated with the level of the partner with lowest concentration,
      demonstrating that the anti-apoptotic effect previously attributed to each
      proteins was in fact borne by the p8/ProTalpha complex, the two proteins, being
      individually inactive. These results show that the function attributed to a
      natively unfolded protein might actually belong to a multi-protein complex in
      which the protein of interest is engaged.

PMID- 16628002
TI  - Friend or foe? The proteasome in combined cancer therapy.
AB  - The proteasome is a multicatalytic enzyme complex that is responsible for
      degradation of the vast majority of intracellular proteins. Thus, it is involved
      in diverse cellular processes such as proliferation, differentiation and
      apoptosis. Especially its latter function yielded in the development of specific
      proteasomal inhibitors which have recently entered clinical trials due to their
      tremendous apoptosis-inducing capability. However, several recent studies
      including ours provided substantial evidence that a combined treatment of tumors
      with apoptosis-inducing agents and proteasomal inhibitors might even cause
      adverse effects leading to a prolonged survival of tumor cells. Based on our
      model of a biphasic role for the proteasome in apoptosis, we believe that a
      successful combat of tumors that relies on a combinational therapy with
      proteasomal inhibitors requires careful evaluation of several critical aspects in
      order to avoid a friend becoming a foe.

PMID- 16628003
TI  - Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP
      1 in response to DNA damage.
AB  - Cell survival after genotoxic stress is determined by a counterbalance of pro-
      and anti-death factors. Sirtuins (SIRTs) are deacetylases that promote cell
      survival whereas poly(ADP-ribose) polymerases (PARPs) can act both as survival
      and death inducing factor and the two protein families are strictly dependent on
      NAD(+) for their activities. Here we report that SIRT1 modulates PARP-1 activity
      upon DNA damage. Activation of SIRT1 by resveratrol leads to reduced PARP-1
      activity and there is a drastic increase in PAR synthesis in sirt1-null cells.
      The unbalanced regulation of PARP-1 in the absence of SIRT1 results in AIF
      (apoptosis inducing factor)-mediated cell death. Our findings establish a
      functional link between the two NAD+-dependent enzyme systems and provide a
      physiological interpretation for the mechanism of death in cells lacking SIRT1.

PMID- 16628004
TI  - M-phase MELK activity is regulated by MPF and MAPK.
AB  - The protein kinase MELK is implicated in the control of cell proliferation, cell
      cycle and mRNA splicing. We previously showed that MELK activity is correlated
      with its phosphorylation level, is cell cycle dependent, and maximal during
      mitosis. Here we report on the identification of T414, T449, T451, T481 and S498
      as residues phosphorylated in Xenopus MELK (xMELK) in M-phase egg extract.
      Phosphorylations of T449, T451, T481 are specifically detected during mitosis.
      Results obtained in vivo showed that MPF and MAPK pathways are involved in xMELK
      phosphorylation. In vitro, MPF and MAPK directly phosphorylate xMELK and MPF
      phosphorylates xMELK on T481. In addition, phosphorylation by MPF and MAPK
      enhances MELK activity in vitro. Taken together our results indicate that MELK
      phosphorylation by MPF and MAPK enhance its activity during M-phase.

PMID- 16628005
TI  - Human Sgo1 is an excellent target for induction of apoptosis of transformed
      cells.
AB  - Aneuploidy, a frequent form of genomic instability, is a direct result of mis
      segregation of sister chromatids during mitosis. Cohesion of sister chromatids in
      eukaryotes is primarily achieved by the cohesin complex. Since Sgo1 functions to
      protect centromeric cohesin and since depletion of Sgo1 results in precocious
      chromosomal segregation and massive mitotic arrest, we reasoned that disruption
      of Sgo1 functions by delivery of a competitive peptide could interfere with
      normal cell cycle progression. Treatment of HeLa and A549 cells with a Sgo1
      fragment of 22 amino acids (corresponding to a conserved basic region at the C
      terminus) linked with a cell-permeable peptide penetratin, but not with
      penetratin alone, resulted in concentration-dependent suppression of viability.
      Following 24 h treatment with Sgo1 peptide at a 40 muM final concentration, HeLa
      cell viability was dramatically reduced. The Sgo1 peptide induced rapid and
      drastic changes of cell and nuclear morphologies, which were associated with
      disappearance of cellular Sgo1 at kinetochores in mitotic cells. Moreover, the
      reduction in HeLa cell viability after treatment with Sgo1 peptide resulted from
      induction of apoptosis. Interestingly, WI-38 diploid fibroblasts were rather
      resistant to the treatment with Sgo1 peptide. These normal cells exhibited little
      changes of cellular and nuclear morphologies, and remained viable after exposure
      to 40 muM of Sgo1 peptide for 24 h. Our combined studies thus suggest that small
      peptides corresponding to conserved regions of Sgo1 are capable of functioning as
      dominant negative inhibitors in vivo and that Sgo1 is an excellent target for
      induction of apoptosis of cancer cells.

PMID- 16628006
TI  - 2-deoxy-D-glucose reduces the level of constitutive activation of ATM and
      phosphorylation of histone H2AX.
AB  - Histone H2AX phosphorylated on Ser-139, defined as gammaH2AX, is a reporter of
      DNA double-strand breaks (DSBs). While H2AX undergoes phosphorylation after
      induction of DNA damage by genotoxic agents or during physiological events that
      involve DNA recombination, it also is phosphorylated in untreated normal and
      tumor cells. We recently reported that this constitutive H2AX phosphorylation
      (CHP) is markedly reduced by the antioxidant N-acetyl-L-cysteine (NAC), and
      postulated that it reflects the oxidative DNA damage ("endogenous DSBs") induced
      by reactive oxygen species (ROS) generated by metabolic activity during
      progression through the cell cycle. In the present study, we provide evidence
      that growth of cells from three human lymphoblastoid cell lines TK6, NH32 and
      WTK1 in the presence of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) led
      to a distinct reduction in the level of CHP. The reduction of CHP was more
      pronounced in S and G(2)M than in G(1) phase cells. Constitutive activation of
      ATM was also reduced. The data suggest that a decrease in a cell's metabolic
      activity as a result of inhibition of glycolysis by 2-DG reduces generation of
      ROS which leads to the reduction of oxidative DNA damage. The data also point out
      that ATM may play a role in CHP induced by oxidative DNA damage. Therefore, the
      assay of CHP by multiparameter cytometry provides the means to measure effects of
      antioxidants and metabolic inhibitors on endogenous oxidative DNA damage in
      relation to cell cycle phase.

PMID- 16628007
TI  - Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1
      complex by CRYPTOCHROMES.
AB  - Mammalian CLOCK(NPAS2), BMAL1 and CRYPTOCHROMEs are core components of the
      circadian oscillatory mechanism. The active CLOCK/BMAL1 or NPAS2/BMAL1 complexes
      regulate expression of numerous genes including two Cryptochromes. The products
      of these genes, CRY1 and CRY2, in turn repress CLOCK/BMAL1 transcriptional
      activity by an unknown mechanism. We have examined the effect of CRYPTOCHROMEs on
      posttranslational modifications and intracellular distribution of endogenous and
      ectopically expressed CLOCK(NPAS2) and BMAL1 proteins. We found that ectopic
      coexpression with CRY led to stabilization and nuclear accumulation of
      unphosphorylated forms of the proteins, which directly correlated with the
      inhibition of their transcriptional activity. This effect was CRY-specific, as
      other known repressors of CLOCK/BMAL1 and NPAS2/ BMAL1 transcriptional activity
      were not able to induce similar effects. CRYs had no effect on CLOCK(NPAS2)/BMAL1
      complex formation or its ability to bind DNA. Altogether, these results
      demonstrate that CRYs regulate the functional activity of circadian
      transcriptional complex at the posttranslational level. Importantly, the
      posttranslational modifications and intracellular distribution of CLOCK and BMAL1
      proteins were critically impaired in the tissues of mice with targeted disruption
      of both Cry genes, thus confirming the suggested role of CRY in clock function in
      vivo. Based on these findings we propose a modified model of the circadian
      transcriptional control, which implies CRY-mediated periodic rotation of
      transcriptionally active and inactive forms of CLOCK/BMAL1 on the promoter. This
      model provides mechanistic explanation for previously reported dual functional
      activity of CLOCK/BMAL1 and highlights the involvement of the circadian system in
      modulating the organism's response to various types of genotoxic stress,
      including chemotherapy and radiation.

PMID- 16628008
TI  - Clonal expansion in the human gut: mitochondrial DNA mutations show us the way.
AB  - The mechanisms of how DNA mutations are fixed within the human gastrointestinal
      tract and how they spread are poorly understood and are hotly debated. It has
      been well documented that human colonic crypts are clonal units; one epithelial
      stem cell within the crypt becoming dominant and taking over the crypts' entire
      stem cell population--so called monoclonal conversion. Studies have revealed that
      crypts can exist as families and develop into patches. The questions have been
      how do such patches in the human colon develop? Does this have implications on
      how DNA mutations spread? We have previously shown that mitochondrial DNA (mtDNA)
      mutations, which result in the deficiency of cytochrome c oxidase, are
      established within a single colonic crypt stem cell, resulting in a crypt with a
      mixed phenotype. Over time that mutated stem cell can take over the entire stem
      cell population resulting in a wholly-mutated crypt. We have furthered this
      research by showing that entirely cytochrome c oxidase-deficient crypts are able
      to divide by a process called crypt fission, to form two cytochrome c oxidase
      deficient daughter crypts, each sharing the exact parental mtDNA mutation.
      Furthermore, patches of these crypts also possess a founder mtDNA mutation
      suggesting that fission repeats itself to form patches, which increase in size
      with age. Here, we hypothesize that this can be expanded into other areas of the
      gastrointestinal tract, especially the stomach, where there is a paucity of data
      regarding clonality and the spread of DNA mutations. We ask if these mutated
      crypts expand at a different rate to wild type ones. We also discuss the
      implications for the spread of potential carcinogenic mutations within the gut.

PMID- 16628009
TI  - Genesis and wanderings: origins and migrations in asymmetrically replicating
      mitochondrial DNA.
AB  - Mammalian mitochondria maintain a small circular genome that encodes RNA and
      polypeptides that are essential for the generation of ATP through oxidative
      phosphorylation. The mechanism of replication of mammalian mitochondrial DNA
      (mtDNA) has recently been a topic of controversy. New evidence has led to a
      modified strand-displacement model that reconciles much of the current data. This
      revision stems from a new appreciation for alternative light-strand origins. We
      consider here some of the potential mechanisms for light-strand origin
      initiation. We also consider further the susceptibility of branch migration
      within replicating mtDNA molecules. The existence of alternative light-strand
      origins and a propensity for branch migration in replicating mtDNA molecules
      exposes a new array of possible configurations of mtDNA. The assortment and
      assignment of these forms is relevant to the interpretation of experimental data
      and may also yield insight into the molecular basis of replication errors.

PMID- 16628010
TI  - ATF3 regulates the stability of p53: a link to cancer.
AB  - ATF3 is a member of the ATF/CREB family of transcription factors involved in the
      cellular response to a large variety of stresses including DNA damage. However,
      neither the signaling leading to nor the biological significance of its induction
      upon stress is well understood. Although it is generally believed that ATF3
      exerts its function in the stress response by regulating transcription, to date,
      only a limited number of target genes have been identified. We recently reported
      that ATF3 interacts with the tumor suppressor p53 to increase its stability in
      the genotoxic response. While providing the cell a general means of responding to
      diverse adverse environment cues, this mechanism confers ATF3 with an ability to
      promote tumor suppressor functions. Conversely, dysfunction of ATF3 impairs the
      p53-mediated cellular response to DNA damage, allowing cells to be readily
      transformed by oncogenes. Consistent with this notion is the observation of
      downregulated ATF3 expression in most human cancers. Therefore, our findings
      indicate that ATF3 intersects with p53-associated pathways ensuring genomic
      integrity. The ability of ATF3 to stabilize p53-induced pathways thus represents
      a means of effectively countering DNA damage caused by environmental insult the
      latter leading to oncogene activation and ultimately malignant transformation.

PMID- 16628011
TI  - Non-specific detection of the centrosomes by antibodies recognizing
      phosphorylated ATM at serine 1981.

PMID- 16628012
TI  - E2F1 and telomerase: alliance in the dark side.
AB  - Cancer arises from a stepwise accumulation of genetic changes. Among these
      changes, deregulation of the Rb/E2F1 pathway and constitutively active telomerase
      are pivotal milestones for the attainment of immortality and maintaining the
      neoplastic phenotype. We recently showed the Rb/E2F1 pathway to be a direct
      modulator of telomerase activity in normal and cancer cells, specifically in
      malignant gliomas. In addition, we reported that the correlation between the
      levels of expression of E2F1 and hTERT -the catalytic subunit of telomerase- in a
      subset of patients with glioblastoma multiforme confers clinical relevance to the
      role of E2F1 in triggering or maintaining hTERT expression. Here we review the
      evidence supporting the mechanistic linkage between E2F1 and telomerase
      activation. We also consider the clinical implications of this association in
      terms of prognostic significance and opportunities for the development of new and
      more rational therapeutic strategies.

PMID- 16628013
TI  - Cell cycling through Cdc25A: transducer of cytokine proliferative signals.
AB  - A balance between survival and proliferative signals maintains a constant number
      of T lymphocytes that populate the mammalian immune system, a process termed
      "homeostasis". Central to this process is the availability of a stromal cell
      product--the cytokine interleukin-7 (IL-7). We recently showed that IL-7, in
      addition to protecting cells from apoptosis, drives the cell cycling of
      lymphocytes through regulation of the stability of the phosphatase, Cdc25A, a key
      activator of cyclin-dependent kinases (cdks). IL-7 achieves this by controlling
      the activity of p38 MAP kinase (MAPK), which can phosphorylate Cdc25A, triggering
      its degradation. Sustained expression of Cdc25A had diverse effects: it promoted
      cell cycling, even in presence of cell cycle inhibitors such p27Kip1, and
      prevented cell shrinkage in response to cytokine deprivation. Herein we show a
      role for Cdc25A as a transducer of cytokine-driven proliferation and discuss
      novel implications for cell growth from the perspective of the requirements for
      maintenance of lymphocyte homeostasis.

PMID- 16628014
TI  - Common and divergent roles for members of the mouse DCX superfamily.
AB  - The doublecortin-like (DCX) domains serve as protein-interaction platforms. DCX
      tandem domains appear in the product of the X-linked doublecortin (DCX) gene, in
      retinitis pigmentosa-1 (RP1), as well as in other gene products. Mutations in the
      human DCX gene are associated with abnormal neuronal migration, epilepsy, and
      mental retardation; mutations in RP1 are associated with a form of inherited
      blindness, while DCDC2 has been associated with dyslectic reading disabilities.
      Motivated by the possible importance of this gene family, a thorough analysis to
      detect all family members in the mouse was conducted. The DCX-repeat gene
      superfamily is composed of eleven paralogs, and we cloned the DCX domains from
      nine different genes. Our study questioned which functions attributed to the DCX
      domain, are conserved among the different members. Our results suggest that the
      proteins with the DCX-domain have conserved and unique roles in microtubule
      regulation and signal transduction. All the tested proteins stimulated
      microtubule assembly in vitro. Proteins with tandem repeats stabilized the
      microtubule cytoskeleton in transfected cells, while those with single repeats
      localized to actin-rich subcellular structures, or the nucleus. All tested
      proteins interacted with components of the JNK/MAP-kinase pathway, while only a
      subset interacted with Neurabin 2, and a nonoverlapping group demonstrated actin
      association. The sub-specialization of some members due to confined intracellular
      localization, and protein interactions may explain the success of this
      superfamily.

PMID- 16628015
TI  - Wasted work time: management and supervision are key to improving productivity.

PMID- 16628017
TI  - Measuring productivity: why don't we have any universal standards?

PMID- 16628018
TI  - Trends in pediatric nutrition.

PMID- 16628020
TI  - Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic
      heart failure.
AB  - Underlying causes, risk factors, and precipitating causes of heart failure (HF)
      should be treated. Drugs known to precipitate or aggravate HF such as
      nonsteroidal antiinflammatory drugs should be stopped. Patients with HF and a low
      left ventricular ejection fraction (systolic heart failure) or normal ejection
      fraction (diastolic HF) should be treated with diuretics if fluid retention is
      present, with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin
      receptor blocker if the patient cannot tolerate an ACE inhibitor because of
      cough, angioneurotic edema, rash, or altered taste sensation, and with a beta
      blocker unless contraindicated. If severe systolic HF persists, an aldosterone
      antagonist should be added. If HF persists, isosorbide dinitrate plus hydralazine
      should be added. Calcium channel blockers should be avoided if systolic HF is
      present. Digoxin should be avoided in men and women with diastolic HF if sinus
      rhythm is present and in women with systolic HF. Digoxin should be given to men
      with systolic HF if symptoms persist, but the serum digoxin level should be
      maintained between 0.5 and 0.8 ng/mL.

PMID- 16628021
TI  - Management of dyslipidemia in diabetes.
AB  - Diabetes is associated with a high risk of cardiovascular disease. The management
      of dyslipidemia, a well-recognized and modifiable risk factor among patients with
      type 2 diabetes, is an important element in the multifactorial approach to
      prevent coronary heart disease. Diabetic dyslipidemia typically consists of
      elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the
      predominance of small dense low-density lipoprotein (LDL) particles. LDL
      cholesterol (LDL-C) levels in patients with diabetes are similar to those found
      in the rest of the population. During the past few years, clinical trials have
      provided evidence that lipid-lowering therapy has a similar beneficial effect on
      cardiovascular outcomes in diabetic and nondiabetic individuals. According to
      current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in
      very high-risk patients) and, to this end, statins are the agents of choice. The
      appropriate management of dyslipidemia in patients with diabetes, particularly in
      individuals with low LDL-C, remains controversial. To achieve lipid targets,
      attention should be directed first toward nonpharmacologic therapeutic
      interventions to control dyslipidemia, such as diet, exercise, smoking cessation,
      weight loss, and glycemic control. Statin therapy is recommended for most
      subjects but, frequently, a combination of lipid-lowering agents is required. A
      number of combinations are possible, and several factors should be considered to
      improve the safety of this strategy.

PMID- 16628022
TI  - Variability of response to clopidogrel: possible mechanisms and clinical
      implications.
AB  - Clopidogrel has been shown to inhibit adenosine diphosphate-induced platelet
      aggregation and has been demonstrated to be effective in reducing the risk of
      arterial thrombotic events in several large clinical studies. However, the
      clinical benefit could be attenuated by the variability of response to the
      antiplatelet effects of clopidogrel in as many as 30% of patients. Multiple
      mechanisms likely contribute to clopidogrel variability of response, including
      inappropriate dosing or underdosing of clopidogrel, drug-drug interactions, and
      genetic polymorphisms. The best laboratory procedure to screen for possible
      clopidogrel variability of response remains to be determined.

PMID- 16628023
TI  - The paclitaxel-eluting stent in percutaneous coronary intervention: Part II.
      Comparison with the sirolimus-eluting stent, economics, and unanswered questions.
AB  - The paclitaxel- and sirolimus-eluting stents are currently the only drug-eluting
      stents approved for use in the United States. These 2 stents differ in terms of
      mechanism of drug action, the construct of the stent itself, and the drug
      delivery polymer. Clinical trials have demonstrated superiority of both
      paclitaxel- and sirolimus-eluting stents when compared with bare-metal stents in
      terms of reducing restenosis and the need for target vessel revascularization.
      Recently published head-to-head trials have not conclusively shown 1 drug-eluting
      stent to be superior to the other, but have demonstrated more favorable
      angiographic results with the sirolimus-eluting stent compared with the
      paclitaxel-eluting stent; however, no significant difference has been
      demonstrated in clinical outcomes such as myocardial infarction or death. In
      terms of economics, the paclitaxel-eluting stent is substantially more expensive
      than the bare-metal stent. However, by significantly reducing the risk of
      restenosis and need for repeat revascularization, the higher direct cost of the
      paclitaxel-eluting stent may in theory be offset by lower overall healthcare
      costs, although economic analyses have yet to definitively establish that the
      paclitaxel-eluting stent is truly cost-effective. There is still much to be
      discovered regarding the paclitaxel-eluting stent, specifically the optimal stent
      design and drug release mechanism, the relative safety and efficacy of the
      paclitaxel-eluting stent compared with other drug-eluting stents, the long-term
      effects of the paclitaxel-eluting stent, the ideal antiplatelet regimen to use in
      patients with a paclitaxel-eluting stent, the safety and efficacy of the
      paclitaxel-eluting stent in various high-risk patient groups, and the ultimate
      cost-effectiveness of this device.

PMID- 16628024
TI  - Dynamic aortic obstruction in a patient with acute type B dissection.
AB  - There are at least 7000 aortic dissections diagnosed in the United States each
      year. Type B dissections accounted for 38% of cases enrolled in the prospective
      International Registry of Aortic Dissection. We report a case of a 48-year-old
      hypertensive woman with an acute type B aortic dissection causing significant
      dynamic obstruction of the aorta. Intravascular ultrasound of her aorta revealed
      a mobile intimal flap nearly obliterating the true lumen with each systolic
      contraction. Simultaneous pressure tracings obtained from her ascending aorta and
      femoral artery demonstrated a systolic pressure gradient in excess of 100 mm Hg.
      The patient developed progressive renal failure and ultimately underwent
      successful operative replacement of the proximal descending thoracic aorta with a
      Dacron graft. In this case presentation, we highlight the unusual physiology
      exemplified by this case and explore contemporary management strategies for
      complicated type B aortic dissection, including surgery and catheter-based
      techniques.

PMID- 16628025
TI  - Coronary artery dissection during pregnancy treated with medical therapy.
AB  - Spontaneous coronary artery dissection is a rare etiology of myocardial
      infarction with a higher noted incidence in pregnancy. The recognition and proper
      treatment of this condition affects patient outcomes. We report the case of a
      coronary artery dissection during a twin pregnancy involving the left anterior
      descending artery. Successful treatment with medical management was possible once
      spontaneous reperfusion had been achieved.

PMID- 16628026
TI  - Changing conduction abnormalities in a dialysis patient with fever.
AB  - A patient on hemodialysis with severe aortic valve disease and presumed
      arteriovenous fistula infection was found to have new-onset atrial fibrillation
      and alternating left and right bundle branch block patterns on serial
      electrocardiograms. These findings prompted transesophageal echocardiography,
      which revealed a large abscess involving the intervalvular fibrosa and the
      posterior cusp of the bicuspid aortic valve. Hence, basic bedside diagnostic
      skills remain important in the era of sophisticated imaging techniques and
      laboratory analyses.

PMID- 16628027
TI  - Detection of portal perfusion abnormalities: comparison of 3 ferucarbotran
      enhanced magnetic resonance imaging sequences.
AB  - OBJECTIVE: To estimate the accuracy, sensitivity, and specificity of 3
      ferucarbotran-enhanced magnetic resonance (MR) imaging sequences prospectively
      for the detection of nontumoral portal perfusion abnormalities. METHODS: Thirty
      nine noncirrhotic patients with liver metastases underwent computed tomography
      during arterial portography (CTAP) and MR imaging comprising T1-weighted gradient
      recalled echo (GRE), T2-weighted fast spin echo (FSE), and T2*-weighted GRE
      sequences with and without ferucarbotran. Magnetic resonance images were reviewed
      by 4 blinded observers for rating based on the confidence scale. The accuracy,
      sensitivity, and specificity for each sequence were measured by receiver
      operating characteristic analysis. Contrast-to-noise ratio (CNR) and relative
      signal-to-noise ratio changes were statistically compared. RESULTS: Thirty-nine
      nontumoral perfusion defects were observed in 22 patients by CTAP. Receiver
      operating characteristic analysis showed the accuracy was higher for T2*-weighted
      GRE (0.884) than for T1-weighted GRE (0.572) and T2-weighted FSE (0.597). T2*
      weighted imaging achieved the highest sensitivity (81.4%) and the lowest
      specificity (86.6%). Postenhanced T2*-weighted imaging achieved the highest CNR
      (19.3 +/- 9.2). CONCLUSIONS: T2*-weighted imaging was the most accurate and
      sensitive method for detecting portal perfusion abnormalities compared with T1-
      or T2-weighted imaging, whereas T1- or T2-weighted imaging is superior in
      specificity to T2*-weighted imaging during ferucarbotran-enhanced MR imaging.

PMID- 16628028
TI  - CT features of an intraductal polypoid mass: Differentiation between
      hepatocellular carcinoma with bile duct tumor invasion and intraductal papillary
      cholangiocarcinoma.
AB  - OBJECTIVE: To determine the CT features capable of differentiating hepatocellular
      carcinoma (HCC) with bile duct tumor invasion (BDTI) from intraductal
      cholangiocarcinoma (IDCC). METHODS: Multiphasic CT images of 14 patients with HCC
      with BDTI and 18 patients with IDCC were retrospectively reviewed. Analysis of
      the CT findings included the size, location, and margin of the intraductal mass,
      the enhancement pattern of intraductal lesions, degree of ductal dilatation,
      presence of downstream ductal dilatation and ductal wall thickening, presence of
      parenchymal mass and its size, continuity of parenchymal mass with intraductal
      mass, and liver cirrhosis. Objective evaluation of the enhancement patterns of
      intraductal tumors was done by measuring the CT attenuation coefficients of the
      tumors and the uninvolved hepatic parenchyma in each phase. Among these findings,
      statistically significant variables were then determined using Fisher exact test
      or Mann-Whitney test. RESULTS: Significant variables that helped differentiating
      HCC with BDTI from IDCC included the presence of parenchymal mass, liver
      cirrhosis, and the hyperattenuating intraductal tumor on the hepatic arterial
      phase (HAP). On unenhanced images, the tumor-to-liver contrast of IDCC (16.7 +/-
      8.1) was greater than that of HCC with BDTI (6.4 +/- 10.4), but on HAP, that of
      HCC with BDTI (26.5 +/- 28.2) was greater than that of IDCC (5.9 +/- 18.7) (P <
      0.05). In addition, there was a significant difference in the enhancement ratio
      of the intraductal tumors on portal venous phase (PVP) between the 2 conditions
      (P = 0.003). CONCLUSIONS: Several objective and subjective multiphasic CT
      findings may help differentiating HCC with BDTI from IDCC.

PMID- 16628029
TI  - Optimal delay time for the hepatic parenchymal enhancement at the multidetector
      CT examination.
AB  - The objective of this study was to determine the optimal scan delay time after
      hepatic parenchymal enhancement using a 16-channel multidetector row helical CT
      (MDCT) scanner. Two hundred fifty-five consecutive patients underwent biphasic CT
      scans using a 16-channel MDCT. In group A (n = 125), two hepatic venous phase
      scans (HVP1 and HVP2) were obtained at 40 and 60 seconds, after 100-HU threshold
      time (T100HU) in the abdominal aorta. In group B (n = 130), HVP1 and HVP2 scans
      were obtained 50 and 70 seconds after T100HU. Both groups were divided into
      subgroups that were given different contrast media. Groups A1 and B1 received a
      contrast medium of 300 mgI/mL; groups A2 and B2 received a contrast medium of 370
      mgI/mL. Each patient was injected with contrast medium at a dose of 2 mL/kg at a
      rate adjusted to the patient's body weight with a constant injection duration of
      47 seconds. The attenuation values (HU) for the liver, portal vein, hepatic vein,
      and aorta were measured. The average HU was compared between the groups. Hepatic
      enhancement in the images obtained at 50 and 60 seconds after T100HU was greater
      (P < 0.05) than in images obtained at 40 and 70 seconds. These results were
      obtained with both contrast media. A few patients showed greater enhancement at a
      40 seconds or 70 seconds. Hepatic enhancement was significantly greater in all
      scans using a contrast medium dose of 370 mgI/mL compared with the 300-mgI/mL
      dose (P < 0.05). Independent of the concentration of contrast medium, scan delays
      of 50 to 60 seconds after T100HU may provide optimal hepatic enhancement.

PMID- 16628030
TI  - Solid organizing hepatic abscesses mimic hepatic tumor: Multiphasic computed
      tomography and magnetic resonance imaging findings with histopathologic
      correlation.
AB  - OBJECTIVE: To describe the computed tomography (CT) and magnetic resonance
      imaging (MRI) findings of solid organizing hepatic abscesses and correlate them
      with the pathologic findings. METHODS: Ten patients with 10 pathologically proven
      solid organizing hepatic abscesses who underwent 3-phase CT (n = 10) or MRI (n =
      7) were enrolled in this study. Images were retrospectively analyzed by consensus
      of 2 radiologists for attenuation (signal intensity), shape, and margin of the
      lesions as well as for their enhancement patterns. Their imaging findings were
      correlated with their pathologic findings. RESULTS: The main imaging finding on
      CT or MRI was the well-defined target appearance of a central enhancing area with
      a low-attenuation (signal intensity) rim on arterial and portal phases. On the
      delayed phase, most of lesions showed slightly low attenuation (signal intensity)
      with an enhancing rim, and 1 showed diffuse enhancement. Pathologically, the
      central areas and peripheral rims corresponded to granulation tissue and
      fibrosis, respectively. Nine lesions demonstrated a tiny necrotic cystic portion
      in the center. CONCLUSION: The target appearance of solid organizing hepatic
      abscesses on CT and MRI can be helpful in differentiating them from other focal
      liver lesions. These imaging findings are well correlated with the pathologic
      findings.

PMID- 16628031
TI  - Evaluation of super paramagnetic iron oxide-enhanced diffusion-weighted PROPELLER
      T2-fast spin echo magnetic resonance imaging: Preliminary experience.
AB  - OBJECTIVE: To evaluate the usefulness of super paramagnetic iron oxide-enhanced,
      diffusion-weighted, periodically rotated overlapping parallel lines with enhanced
      reconstruction (SPIO DWI PROPELLER) T2-fast spin echo (FSE) magnetic resonance
      imaging (MRI) for the detection of hepatic metastases. METHODS: Fourteen patients
      were examined with SPIO-enhanced T2-FSE (SPIO FSE) imaging and SPIO DWI PROPELLER
      T2-FSE imaging. The b-value of the diffusion-sensitizing gradient was 10 s/mm so
      as to suppress the signal of the hepatic vessels. Hepatic resections were
      performed on all patients, and the number of lesions on MRI was compared between
      the 2 pulse sequences with references from pathologic reports. RESULTS: Nearly
      all metastases 1 cm or larger, totalling 38 metastases, were detected with both
      pulse sequences. Among the 30 metastases less than 1 cm, more lesions were
      detected on SPIO DWI PROPELLER T2-FSE imaging than on SPIO FSE imaging (16 for
      SPIO FSE imaging and 24 for DWI PROPELLER T2-FSE imaging; P < 0.05, McNemar
      test). CONCLUSION: Super paramagnetic iron oxide-enhanced DWI PROPELLER T2-FSE is
      useful for detecting small hepatic metastases.

PMID- 16628032
TI  - Density histogram analysis of unenhanced hepatic computed tomography in patients
      with diffuse liver diseases.
AB  - OBJECTIVE: The aim of the study was to assess the potential of density histogram
      analysis of unenhanced hepatic computed tomography (CT) in the diagnosis and
      differentiation of diffuse liver diseases. METHODS: Twenty-six patients with
      normal liver parenchyma, 35 patients with diffuse steatosis, 14 patients with
      acute steatohepatitis, 15 patients with active alcoholic cirrhosis, 23 patients
      with inactive alcoholic cirrhosis, 15 patients with virus-induced cirrhosis, and
      8 patients with hemochromatosis underwent unenhanced hepatic CT. All diffuse
      liver diseases and the absence of diffuse liver disease were histologically
      proven. Quantitative analysis of unenhanced liver parenchyma was performed in
      each patient. RESULTS: The hepatic density histogram showed no significant
      differences in kurtosis and skewness between the groups (P > 0.05). Except for
      steatosis, active alcoholic cirrhosis, and hemochromatosis, diffuse liver
      diseases led to similar densities of liver parenchyma in unenhanced hepatic CT.
      CONCLUSION: A reliable diagnosis and differentiation of diffuse liver diseases on
      the basis of density histogram analysis is not possible.

PMID- 16628033
TI  - Determining the optimal timing for early arterial phase hepatic CT imaging by
      measuring abdominal aortic enhancement in variable contrast injection protocols.
AB  - OBJECTIVE: To find the optimal scan timing for early arterial phase hepatic CT
      with adequate arterial enhancement after the aortic contrast arrival. METHODS:
      Sixty patients were divided randomly into three groups, each of which received
      2.0 mL/kg of the 300 mgI/mL contrast medium with an injection duration of 30
      seconds (Group A, mean rate 3.6 mL/sec); of 25 seconds (B, 4.6 mL/sec); of 30
      seconds (3.6 mL/sec) followed by a saline chaser (C). RESULTS: After the contrast
      arrival, aortic enhancement increased rapidly for 6-15 seconds (mean, 10 seconds)
      to the initial peak enhancement in all groups, and then, increased moderately to
      the maximum aortic enhancement over the following 19, 13, and 21 seconds,
      respectively. The mean maximum aortic enhancement in Group B (392 HU) and C (360
      HU) were significantly higher than that in A (326 HU), respectively. The
      difference between the initial and maximum aortic enhancement was less than 50
      HU. CONCLUSION: The optimal timing of the early arterial phase for hepatic CT
      arteriography is 10-15 seconds after the aortic arrival.

PMID- 16628034
TI  - Volumetric analysis of liver metastases in computed tomography with the fuzzy C
      means algorithm.
AB  - Tumor size is often determined from computed tomography (CT) images to assess
      disease progression. A study was conducted to demonstrate the advantages of the
      fuzzy C-means (FCM) algorithm for volumetric analysis of colorectal liver
      metastases in comparison with manual contouring. Intra-and interobserver
      variability was assessed for manual contouring and the FCM algorithm in a study
      involving contrast-enhanced helical CT images of 43 hypoattenuating liver lesions
      from 15 patients with a history of colorectal cancer. Measurement accuracy and
      interscan variability of the FCM and manual methods were assessed in a phantom
      study using paraffin pseudotumors. In the clinical imaging study, intra-and
      interobserver variability was reduced using the FCM algorithm as compared with
      manual contouring (P = 0.0070 and P = 0.0019, respectively). Accuracy of the
      measurement of the pseudotumor volume was improved using the FCM method as
      compared with the manual method (P = 0.047). Interscan variability of the
      pseudotumor volumes was measured using the FCM method as compared with the manual
      method (P = 0.04). The FCM algorithm volume was highly correlated with the manual
      contouring volume (r = 0.9997). Finally, the shorter time spent in calculating
      tumor volume using the FCM method versus the manual contouring method was
      marginally statistically significant (P = 0.080). These results suggest that the
      FCM algorithm has substantial advantages over manual contouring for volumetric
      measurement of colorectal liver metastases from CT.

PMID- 16628035
TI  - Ectopic thyroid in the adrenal gland: Computed tomography findings.
AB  - Ectopic thyroid in the adrenal gland is extremely rare, and its radiologic
      findings have not been reported in the radiologic literature. A case of ectopic
      thyroid in the adrenal gland is reported, and its imaging findings on computed
      tomography are discussed.

PMID- 16628036
TI  - Eccrine acrospiroma of inguinal area: Computed tomography findings.
AB  - Eccrine acrospiroma is a tumor originating from the sweat glands. The computed
      tomography findings of eccrine acrospiroma in the right inguinal area are
      presented. In our case, the tumor was seen as a well-defined and ovoid-shaped
      cystic mass with an internal enhancing solid portion and containing
      calcifications. Eccrine acrospiroma should be considered in the differential
      diagnosis of a subcutaneous cystic mass with an internal solid nodule.

PMID- 16628037
TI  - Delayed hyperenhancement by contrast-enhanced magnetic resonance imaging:
      Clinical application for various cardiac diseases.
AB  - The clinical applications of contrast-enhanced magnetic resonance (MR) imaging
      for defining viability are evolving as a result of the advantage of the
      technique's excellent spatial resolution. The value of delayed hyperenhancement
      imaging is for the accurate identification of the infarcted myocardium with
      resolution that allows determination of the transmural extent of myocardial
      injury. In addition, nonischemic patterns of myocardial injury such as dilated or
      hypertrophic cardiomyopathy have been reported in other disease states. Delayed
      hyperenhancement may have an additional role in guiding the management of or
      determining the prognosis for diseases such as myocarditis. In this study, the
      clinical application of delayed hyperenhancement is demonstrated for various
      cardiac diseases such as myocardial infarction, including right ventricular
      infarction; microvascular obstruction; and nonischemic cardiomyopathy such as
      dilated cardiomyopathy and myocarditis.

PMID- 16628038
TI  - Evaluation of pulmonary embolisms using coronal reformations on 64-row
      multidetector-row computed tomography: Comparison with axial images.
AB  - OBJECTIVE: To evaluate coronal reformations of the chest on 64-row multidetector
      row computed tomography (MDCT) for detection of pulmonary embolisms compared with
      axial images. METHODS: Thirty-eight consecutive patients who underwent pulmonary
      computed tomography angiography (CTA) on 64-row MDCT for a suspected pulmonary
      embolism were retrospectively studied. Contiguous 2-mm axial and coronal images
      were reviewed independently. A pulmonary embolism was assessed in the main,
      lobar, or segmental pulmonary arteries and was scored using a 5-point scale.
      RESULTS: A pulmonary embolism was demonstrated in 10% (4 of 38) of axial images
      and 16% (6 of 38) of coronal images. Interpretation was concordant in 95% to 100%
      of cases for a main or lobar pulmonary embolism and in 80% to 82% of cases for a
      segmental pulmonary embolism. Agreement of scores was almost perfect for a a main
      or lobar pulmonary embolism (mean weighted kappa value = 0.969) and moderate to
      good for a segmental pulmonary embolism (mean weighted kappa value = 0.560).
      CONCLUSION: Coronal reformations of the chest on 64-row MDCT were as informative
      as axial images for the detection of main, lobar, and segmental pulmonary
      embolisms.

PMID- 16628039
TI  - Endovascular therapy of pulmonary arteriovenous malformations: Utility of 16
      detector-row computed tomography pulmonary angiography as a pre-embolization
      survey.
AB  - The utility of computed tomography pulmonary angiography (CTPA) for coil
      embolization therapy of pulmonary arteriovenous malformations (PAVMs) was
      considered. Three consecutive patients (group A) with PAVMs underwent CTPA and
      coil embolization. The CTPA was performed using a 16-detector-row computed
      tomography scanner. After careful selection of pulmonary vessel trees, each
      feeding artery, nidus, and drainage vein was colored using different codes. By
      using the colored images, a 5-French catheter was shaped to fit to each feeding
      artery, the best fluoroscopic angle to select each feeding artery was chosen, and
      interlocking detachable coils (IDCs) were used in embolization. The procedure
      time and contrast material dose of group A were compared with those of the
      previous 3 patients (group B) who were treated by the conventional method. All
      PAVMs of both groups were completely embolized without coil migration. The
      average procedure time per lesion was 48.4 minutes for group A and 124.0 minutes
      for group B (P < 0.05). The average contrast material dose per lesion was 37.5 mL
      in group A and 76.0 mL in group B (P < 0.05). Using CTPA and IDCs, procedure time
      and contrast material dose were statistically significantly reduced. This
      combination therapy is useful in treating PAVMs less invasively.

PMID- 16628040
TI  - Quantitative analysis for computed tomography findings of various diffuse lung
      diseases using volume histogram analysis.
AB  - OBJECTIVES: : The aim of this study was to achieve the quantitative analysis of
      the characteristic computed tomography (CT) findings and course of interstitial
      pneumonia using the volume histogram method. METHODS: : Contrast (CNT), variance
      (VAR), and entropy (EPY) values from whole-lung volume data were compared between
      normal lungs and 5 diseases that have characteristic CT findings. Thirteen cases
      with nonspecific interstitial pneumonia (NSIP) were evaluated before and after
      treatment. RESULTS: : In cases with thickening of the bronchovascular bundles and
      interlobular thickening, ground-glass attenuation, airspace consolidation, and
      honeycombing, the values of VAR and EPY were greater than those in the normal
      cases (P < 0.05). In the cases with NSIP, the CNT value after treatment was
      significantly greater and the values of VAR and EPY after treatment were
      significantly lower than those before treatment (P < 0.05). CONCLUSIONS: : Volume
      histogram analysis is a promising method for the evaluation of diffuse lung
      diseases and the effectiveness of treatment.

PMID- 16628041
TI  - Magnetic resonance imaging of a coronary fistula manifesting as a pericardial
      effusion.
AB  - A case of a congenital fistulous communication between the left circumflex
      coronary artery and coronary sinus that presented as a pericardial effusion and
      was diagnosed using a comprehensive cardiac magnetic resonance imaging (MRI)
      evaluation is presented. This is an unusual presentation of an uncommon
      condition, and the MRI features have not been described previously. Noninvasive
      cardiac assessment via MRI allows for identification of the anatomic basis and
      functional consequences of an unusual anomaly such as a coronary artery fistula.

PMID- 16628042
TI  - Nodular pattern at lung computed tomography in fat embolism syndrome: a helpful
      finding.
AB  - The purpose of this study is to describe the computed tomography (CT) findings in
      pulmonary fat embolism syndrome (FES). The chest radiographs and CT scans of 5
      patients with the diagnosis of FES as determined by the presence of at least 1
      major and 4 minor criteria were reviewed. The radiologic features included ground
      glass opacities, with different patterns of presentation seen in all patients.
      Three patients presented with alveolar opacities, and small (<1 cm) ill-defined
      nodules were seen in 4 of 5 patients. In the context of a patient with previous
      trauma and the clinical suspicion of FES, the presence of nodules at CT
      examination may be a helpful finding in the diagnosis of this entity. The chest
      radiographs and CT scans of 5 patients with the diagnosis of FES as determined by
      the presence of at least 1 major and 4 minor criteria as defined by Gurd and
      Wilson were reviewed.

PMID- 16628043
TI  - Effect of the reconstruction window obtained at the isovolumic relaxation period
      on the image quality in electrocardiographic-gated 16-multidetector-row computed
      tomography coronary angiography studies.
AB  - OBJECTIVE: To evaluate whether images obtained during the reconstruction window
      responding to the isovolumic relaxation period could be used for rapid and easy
      postprocessing. METHODS: One hundred ten consecutive patients with suspected
      coronary artery disease who had previously had a multidetector computed
      tomography (MDCT) scan for imaging coronary arteries were enrolled in this study.
      The age of the patients was 59 +/- 13 years (range: 33-78 years), and 77 (70%)
      were male. Multidetector computed tomography was performed on a 16-detector-row
      computed tomography scanner during 1 breath hold (16-24 seconds). Seven different
      sets of images reconstructed at every 10% of the R-R interval from 30% to 90% for
      contrast-enhanced scans at levels containing the first several centimeters of the
      left and right coronary arteries were analyzed. The best of these reconstruction
      windows were then compared with the images reconstructed at the isovolumic
      relaxation period, which is the last portion of the T wave at the end of the
      systole, where there is not any change in ventricular volume, which causes
      stepladder artifacts. The step artifact was classified as excellent, good, or
      poor. Image quality was assessed by 2 radiologists who were not aware of each
      other's interpretation. RESULTS: According to the routinely used reconstructions,
      there were 76 patients with excellent image quality, 28 with good image quality,
      and 6 with poor image quality. For the period of isovolumic relaxation, there
      were 74 patients with excellent image quality, 25 with good image quality, and 11
      with poor image quality. CONCLUSION: If one begins image analysis with the
      isovolumic relaxation period reconstruction window, spending less time for
      postprocessing analyses, good image quality can be obtained such as with other
      good reconstruction windows.

PMID- 16628044
TI  - Computed tomography evaluation of right heart dysfunction in patients with acute
      pulmonary embolism.
AB  - PURPOSE: To evaluate the role of qualitative assessment of right heart
      dysfunction on multidetector computed tomography (CT) in patients with acute
      pulmonary embolism. METHODS: Seventy-four consecutive adults with pulmonary
      embolism diagnosed on multidetector nongated CT were identified between July 2002
      and March 2004. There were 47 women and 27 men, with a mean age of 62 years. Each
      CT scan was jointly reviewed by 2 of 3 reviewers in consensus. The CT scans were
      qualitatively assessed for dilatation of the right ventricle and the position of
      the interventricular septum. Scans were considered positive for right heart
      dysfunction if, on visual integration of multiple axial images, the right
      ventricle was dilated or the interventricular septum was straightened or bowed
      into the left ventricle. The extent of pulmonary vascular obstruction was graded
      using the CT clot burden scoring system. Reports of echocardiograms (n = 30) were
      reviewed when available. The sensitivity and specificity of CT and
      echocardiography in demonstrating right heart dysfunction were calculated and
      compared using pulmonary vascular obstruction of > or =30% as the reference
      standard. RESULTS: Sixty-six percent (49 of 74 patients) with pulmonary embolism
      had right heart dysfunction on CT, with right ventricular dilatation in 38
      patients and septal straightening or bowing in 44 patients. Forty-nine percent
      (36 of 74 patients) had pulmonary vasculature obstruction of > or =30%. There was
      a significant difference between the mean clot burden of patients with (12.8) and
      without (7.5) right heart dysfunction on CT (P = 0.0021). The sensitivity and
      specificity of CT in demonstrating right heart dysfunction were 81% (29 of 36
      patients) and 47% (18 of 38 patients), respectively. Forty-one percent (30 of 74
      patients) had technically adequate echocardiograms within 48 hours of CT. Fifty
      seven percent (17 of 30) of the echocardiograms were positive for right heart
      dysfunction. There was no significant difference between the mean clot burden of
      patients with (12.7) and without (10.3) right heart dysfunction on
      echocardiography. Echocardiography had a sensitivity of 56% (10 of 17 patients)
      and a specificity of 42% (5 of 13 patients) in demonstrating right heart
      dysfunction. CONCLUSION: Qualitative assessment of the cardiac chambers is a
      quick and practical means of evaluating for right heart dysfunction on CT.
      Computed tomography findings of right heart dysfunction in patients with acute
      pulmonary embolism compare favorably with echocardiography and correlate with a
      higher mean pulmonary arterial clot burden. Because most patients do not undergo
      echocardiography, chest CT often provides the only opportunity to evaluate for
      right heart dysfunction in patients with acute pulmonary embolism.

PMID- 16628045
TI  - Percutaneous needle biopsy in single lung patients.
AB  - The occurrence of complications such as pneumothorax after a transthoracic needle
      biopsy is well known. This event may be life threatening in patients with a
      single aerated lung, thus altering the risk/benefit assessment of the physician
      when considering whether to attempt an otherwise indicated biopsy. We review our
      results in 6 single-lung patients who underwent a transthoracic needle biopsy for
      pulmonary nodules.

PMID- 16628046
TI  - Visualization of lymphatic basin from the tumor using magnetic resonance
      lymphography with superparamagnetic iron oxide in patients with thoracic
      esophageal cancer.
AB  - OBJECTIVE: To evaluate magnetic resonance (MR) lymphography with submucosal
      injection of superparamagnetic iron oxide (SPIO) for imaging lymphatic pathways
      from thoracic esophageal cancer. METHODS: In 24 patients with esophageal cancer,
      SPIO was injected into the submucosal layer of the peritumoral region
      endoscopically and MR lymphography was conducted. In study 1, fast spoiled
      gradient-recalled acquisition using a steady-state (FSPGR) sequence was performed
      from the neck to the upper abdomen before and at 20, 40, and 60 minutes after
      injection in 10 patients. In study 2, FSPGR and spin echo T1-weighted images were
      obtained after injection in 14 patients. Areas scanned were the neck to the upper
      mediastinum and the upper abdomen. RESULTS: In study 1, at 20 minutes after
      injection, the signal of each lymph node appeared attenuated when compared with
      precontrast images. The signal-to-noise ratio in lymph nodes exhibiting influx of
      SPIO was significantly lower than that found on precontrast images (P < 0.0005).
      In study 2, influx to the neck lymph nodes was detected in 8 patients (64.3%),
      whereas influx to the upper abdominal lymph nodes was detected in 13 (92.9%).
      CONCLUSIONS: Magnetic resonance lymphography with SPIO could visualize the
      lymphatic pathways draining from the injection site and the location of lymph
      nodes exhibiting influx of SPIO in patients with thoracic esophageal cancer.

PMID- 16628047
TI  - Wandering pleuropericardial cyst.
AB  - Change in position of a chest mass is considered virtually pathognomonic of a
      solitary fibrous tumor of the pleura. Rarely, however, a pleuropericardial cyst
      may manifest as a mobile chest lesion. The computed tomography appearance and
      imaging characteristics of a "wandering" pleuropericardial cyst are discussed.

PMID- 16628048
TI  - A case of lymphangioleiomyomatosis affecting the supraclavicular lymph nodes.
AB  - The case of a 46-year-old woman with lymphangioleiomyomatosis (LAM) involving the
      supraclavicular, mediastinal, and pelvic lymph nodes in addition to the lungs is
      reported. Computed tomography incidentally revealed multiple thin-walled
      pulmonary cysts and low-attenuating masses in the supraclavicular, mediastinal,
      and retroperitoneal lymph nodes. A biopsy of the supraclavicular mass was
      performed and diagnosed as LAM histopathologically. The common sites of
      extrapulmonary LAM include retroperitoneal and mediastinal lymph nodes; however,
      supraclavicular lymph node involvement is extremely rare.

PMID- 16628049
TI  - Temporal subtraction of thin-section thoracic computed tomography based on a 3
      dimensional nonlinear geometric warping technique.
AB  - The authors developed a computer system that automatically produces temporal
      subtraction images on thin-section thoracic computed tomography based on a 3
      dimensional nonlinear geometric warping technique. The automated subtraction
      system was applied to data from 20 subjects with lung diseases. Nineteen (95%) of
      20 results showed good or excellent image quality. The remaining 1 (5%) showed
      adequate image quality. Our preliminary computer system demonstrates the
      potential for a clinically useful automated subtraction system.

PMID- 16628050
TI  - Proton magnetic resonance spectroscopy of mesial temporal sclerosis: Analysis of
      voxel shape and position to improve diagnostic accuracy.
AB  - OBJECTIVE: To determine if change in voxel shape and position improves the
      lateralization of magnetic resonance (MR) spectroscopy to the side of the MR
      imaging and/or electroencephalography (EEG) abnormality in mesial temporal
      sclerosis. METHODS: In 10 patients with unilateral mesial temporal sclerosis and
      5 controls, MR spectroscopy was performed. Long echo time single-voxel
      spectroscopy was obtained in the right and left hippocampus. First, the standard
      2-cm x 2-cm x 2-cm cubic voxels were placed bilaterally. Then, 1-cm x 2-cm x 4-cm
      rectangular voxels were used. With this rectangular voxel shape, more of the
      hippocampus and less of the adjacent medial temporal lobe were included in the
      interrogation voxel. N-acetylaspartate-to-creatine (NAA/Cr) ratios and choline-to
      creatine (Cho/Cr) ratios were obtained. The difference between the affected and
      unaffected sides in the patients was calculated and compared with the controls.
      Additionally, the mean difference and standard deviation were determined.
      Predictive values and Student t tests were also performed. RESULTS: In all 10
      patients, using the NAA/Cr ratios, the rectangular voxel correctly identified the
      abnormal side. The cubic voxel only identified the abnormal side in 6 of the 10
      patients, however. Additionally, the mean difference between the affected and
      unaffected sides was 0.30 for the rectangular voxel but only 0.003 for the cubic
      voxel; that is, there was no overall significant difference when using the cubic
      voxel (P = 0.007). No significant correlation between the affected and unaffected
      sides was found using the Cho/Cr ratios. No significant difference between the
      right and left sides was found in the controls. CONCLUSION: Use of a 1-cm x 2-cm
      x 4-cm rectangular voxel places more of the hippocampus in the region of
      interrogation with less partial volume artifact from the adjacent brain
      parenchyma, which occurs with use of the standard 2-cm x 2-cm x 2-cm cubic voxel,
      resulting in improved correct lateralization of MR spectroscopy to the side of
      the MR imaging and/or EEG abnormality.

PMID- 16628051
TI  - Comparison of magnetic resonance imaging sequences with computed tomography to
      detect low-grade subarachnoid hemorrhage: Role of fluid-attenuated inversion
      recovery sequence.
AB  - OBJECTIVES: To compare computed tomography (CT) with magnetic resonance imaging
      (MRI) for the presumptive diagnosis and localization of acute and subacute low
      grade subarachnoid hemorrhage (SAH). METHODS: We consecutively enrolled 45
      patients clinically suspected of low-grade SAH, comparing them with a control
      group. We obtained axial nonenhanced CT scans as well as fluid-attenuated
      inversion recovery (FLAIR) and T2-weighted gradient echo (T2*) MRI sequences at
      1.0 T. Two neuroradiologists scrutinized the presence of blood at 26 different
      regions in the intracranial subarachnoid space (SAS). RESULTS: Three of 45
      patients had normal CT and MRI scans, and SAH was excluded by lumbar puncture. We
      demonstrated SAH on CT scans in 28 of 42 (66.6%) patients, T2* sequences in 15 of
      42 (35.7%) patients, and FLAIR sequences in 42 of 42 (100%) patients. Fluid
      attenuated inversion recovery sequences were superior to CT in 16 of the 26
      evaluated regions. CONCLUSIONS: The FLAIR sequence was superior for presumptive
      diagnosis and localization of acute and subacute low-grade SAH, representing a
      potential tool in this setting.

PMID- 16628052
TI  - Myelin water fraction in human cervical spinal cord in vivo.
AB  - The noninvasive discrimination of myelin disease from axonal loss and other
      pathologic confounds remains an unsolved problem in multiple sclerosis but may be
      possible through magnetic resonance quantitation of the intramyelinic water
      compartment. Technical challenges have limited the study of this approach in the
      spinal cord, a common site of involvement in multiple sclerosis. This technical
      note reports the test-retest reproducibility of a short T2-based estimate of
      myelin content in human spinal cord in vivo.

PMID- 16628053
TI  - Evaluation of cerebral hemodynamics with computed tomography perfusion using
      gadolinium as an alternative to iodinated contrast: a case report.
AB  - Computed tomography (CT) perfusion is traditionally performed using iodinated
      contrast, but this can be problematic in patients with impaired renal function or
      contrast allergy. We report a case of a 63-year-old man whose medical history was
      complicated by chronic renal failure, which was exacerbated after placement of a
      left cervical internal carotid artery stent by 70% stenosis and left hemisphere
      perfusion deficit. On a follow-up clinic visit, because of the patient s chronic
      renal failure, CT perfusion was performed successfully using gadolinium without
      further renal complications.

PMID- 16628054
TI  - Shock thyroid: A new manifestation of the hypovolemic shock complex in trauma
      patients.
AB  - The authors describe a new computed tomography finding associated with
      significant thoracoabdominal trauma: thyroidal and perithyroidal edema and fluid
      without evidence for direct thyroid injury. It does not seem to be related to
      direct or indirect thyroid injury but is rather a secondary finding related to
      the hypovolemic shock complex. The physiology of this phenomenon is unknown, but
      it is likely to be an additional component to the imaging findings of the
      hypovolemic shock complex. This finding should be recognized so as to avoid
      confusion with thyroid or vascular injury or other incidental etiology.

PMID- 16628055
TI  - Intervertebral disk cyst: a case report.
AB  - This case describes a patient who presented with chronic low back pain which
      developed over the course of 1 year. Imaging revealed a 1.1-cm cystic lesion at
      the L4-L5 vertebral level posterior to the intervertebral disk. Following both
      magnetic resonance and computed tomography imaging, diagnosis of intervertebral
      disk cyst was confirmed by both imaging modalities. A computed tomography-guided
      aspiration of the lesion was performed, and the patient was given a course of
      steroid injections with complete resolution of the lesion.

PMID- 16628056
TI  - Range of normal and abnormal subacromial/subdeltoid bursa fluid.
AB  - OBJECTIVE: To determine the range of normal and abnormal subacromial/subdeltoid
      (SA/SD) bursa fluid. METHODS: Using a 1.5-T magnetic resonance (MR) imaging
      scanner, 2 observers evaluated coronal oblique T2-weighted, fast spin echo, fat
      suppressed images of 71 persons (36 asymptomatic volunteers and 35 patients with
      full-thickness rotator cuff tears [RCTs]) for the 1) widest thickness of the
      SA/SD bursa; 2) medial extent of bursa from the acromioclavicular joint (ACJ);
      and 3) because patients were supine, whether fluid was in the posterior quarter,
      middle quarter, anterior quarter, or anterior-most quarter of the bursa. RESULTS:
      The range of bursa thickness was 0 to 7 mm (mean = 1.3 mm, median = 2 mm) in
      normal bursas and 0 to 8 mm (mean = 3.3 mm, median = 3 mm; P < 0.05, t test) in
      RCTs. Only 2 volunteers exceeded 3 mm in bursa thickness. In volunteers, 36% had
      no fluid present, 61% had a small amount of fluid lateral to the ACJ, and 1 had
      fluid directly beneath the ACJ (P < 0.05). In RCT patients, 37% had fluid
      directly under the ACJ or medial to the ACJ. Only 1 patient with an RCT had no
      bursal fluid. In volunteers, most fluid was in the posterior quarter (53%) or
      middle quarter (22%) of the bursa, whereas in RCT patients, most fluid was
      located in the anterior quarter of the humerus or anterior to the humerus (89%; P
      < 0.05). CONCLUSIONS: Normal SA/SD bursa fluid is rarely thicker than 2 mm and
      tends to be located posteriorly. An abnormal amount of fluid is present when the
      thickness exceeds 3 mm, fluid is present medial to the ACJ, and fluid is seen in
      the part of the bursa anterior to the humerus.

PMID- 16628057
TI  - Magnetic resonance elastography of the plantar fat pads: Preliminary study in
      diabetic patients and asymptomatic volunteers.
AB  - OBJECTIVE: To test the feasibility of applying the magnetic resonance
      elastography (MRE) technique to map the elastic modulus of the plantar fat pads
      in diabetic and nondiabetic subjects. METHODS: A prototype MRE imaging apparatus
      was used to produce quantitative maps of the heel fat pad in a pilot study of 12
      volunteers and 4 patients with diabetes with neuropathy. Anatomic images
      corresponding to MRE maps allowed precise selection of regions of interest in the
      fat. RESULTS: Magnetic resonance elastograms of the heel fat pads were
      successfully created; mean measurements in the volunteers and the diabetic
      patients were 4.85 and 5.26 kPa, respectively. CONCLUSION: It is feasible to
      perform MRE on the plantar fat pads and to produce elasticity maps. The trend
      toward stiffer fat pads, as demonstrated in patients with diabetes, suggests that
      the fat pads were qualitatively different. Magnetic resonance elastography offers
      great potential to investigate the mechanical properties of soft tissues in vivo
      noninvasively.

PMID- 16628058
TI  - Magnetic resonance imaging appearance of a double anterior cruciate ligament
      associated with a displaced tear of the lateral meniscus.
AB  - The aim of this study is to report a novel description of a displaced tear of the
      lateral meniscus as a curvilinear low signal intensity band parallel and
      posteroinferior to the anterior cruciate ligament (ACL) on midline oblique
      sagittal magnetic resonance (MR) images, resulting in the appearance of a "double
      ACL." The appearance of a double ACL may potentially be a specific indicator for
      a lateral meniscal displaced tear. Increased awareness of this characteristic MR
      finding may increase accuracy in the diagnosis of displaced tears of the lateral
      meniscus.

PMID- 16628059
TI  - Hibernomas show intense accumulation of FDG positron emission tomography.
AB  - We present 2 cases of hibernoma. Positron emission tomography using the glucose
      analog [18F]fluoro-2-deoxy-d-glucose (FDG) of 2 patients with hibernoma showed
      intense accumulation. Standardized uptake values (SUVs) in these patients were
      11.93 and 26.74, values much higher than the SUVs reported in published studies
      of liposarcomas. Standardized uptake values of FDG positron emission tomography
      may thus be able to differentiate hibernomas from liposarcomas.

PMID- 16628060
TI  - High-resolution computed tomography of temporal bone: Part III: Axial
      postoperative anatomy.
AB  - The purpose of this 4-part series is to illustrate the nuances of temporal bone
      anatomy using a high-resolution (200-mu isotropic) prototype volume computed
      tomography (CT) scanner. The normal anatomy in axial and coronal sections is
      depicted in the first and second parts. In this and the subsequent part, the
      structures that are removed and/or altered in 9 different surgical procedures are
      color coded and inscribed in the same axial (article III) and coronal (article
      IV) sections. The text stresses clinically important imaging features, including
      the normal postoperative appearance, and common complications after these
      operations. The superior resolution of the volume CT images is vital to the
      comprehensive and accurate representation of these operations. Minuscule
      intricate structures that are currently only localized in the mind's eye because
      of the resolution limit of conventional CT are clearly seen on these scans. This
      enhanced visualization, together with the information presented in the text,
      should assist in interpreting temporal bone scans, communicating with surgeons,
      and teaching this complex anatomy.

PMID- 16628061
TI  - Erythropoietin: a new paradigm for neuroprotection.

PMID- 16628062
TI  - Neuroanesthesiology review--2005.

PMID- 16628063
TI  - The effects of volatile anesthetics on intraoperative monitoring of myogenic
      motor-evoked potentials to transcranial electrical stimulation and on partial
      neuromuscular blockade during propofol/fentanyl/nitrous oxide anesthesia in
      humans.
AB  - The aim of the present study was to compare the influence of volatile anesthetics
      on transcranial motor-evoked potentials (tcMEP) in humans anesthetized with
      propofol/fentanyl/nitrous oxide and on partial neuromuscular blockade (NMB). The
      authors studied 35 ASA I and II patients who were undergoing elective craniotomy
      and brain tumor resection. The patients were randomized to one of three groups to
      receive halothane (HAL), isoflurane (ISO), or sevoflurane (SEV). Anesthetic depth
      was initially adjusted using the bispectral index to 40+/-5, and NMB was adjusted
      to 40%-50% of one twitch of train of four (T1) after recovery from intubation.
      MEPs with train of five square-wave pulses were elicited using screw electrodes
      placed in the skull over C3-C4. After craniotomy, the inhalational agent was
      introduced at 0.5 MAC and then 1.0 MAC (20 minutes each), and the effects on
      MEPs, NMB, and hemodynamic variables were studied. A decrease in BIS and systolic
      blood pressure was observed with all agents. Both SEV and ISO at 1.0 MAC
      significantly decreased train-of-four ratio from 38.4+/-18.1 at control to 19.0+/
      9.7 and from 35.3+/-12.4 to 26.1+/-13.7, respectively (P<0.001), but not HAL at
      1.0 MAC. The amplitudes of tcMEPs were significantly reduced by all agents at 1.0
      MAC, with the effect being less in HAL at 0.5 MAC. We have shown that HAL had a
      lesser suppressive effect on MEPs than either ISO or SEV at 0.5 MAC, which was
      partially due to a lesser degree of NMB.

PMID- 16628064
TI  - Comparison of intracarotid anesthetics for EEG silence.
AB  - The goal of this study was to compare systemic and cerebrovascular effects of
      three anesthetic drugs (etomidate, thiopental, and propofol) when delivered by
      intracarotid and intravenous routes in doses that produce electrocerebral silence
      (electroencephalography [EEG]). EEG activity, mean arterial pressure (MAP), and
      laser Doppler flow as a proxy of cerebral blood flow (CBF) of 24 anesthetized New
      Zealand white rabbits were continuously recorded. Data were compared at three
      timepoints: baseline, during EEG silence, and after recovery of EEG activity.
      Drugs were randomly injected via the carotid artery to produce 10 minutes of EEG
      silence. After 30 minutes of rest, intravenous boluses of the same drug were
      injected to achieve 10 minutes of EEG silence. During EEG silence, transient
      hypotension was seen with intracarotid propofol, but there was no decrease in
      CBF. MAP and CBF did not decrease with either intracarotid etomidate or
      thiopental during EEG silence. Intracarotid/intravenous dose ratio of propofol
      (26%+/-22%; n=8, P<0.02) was much higher than that of etomidate and thiopental
      (14%+/-2% and 19%+/-11%, respectively; NS). Collectively, these results suggest
      intracarotid etomidate and thiopental are more useful than propofol in producing
      EEG silence because they offer better dose advantage and are less likely to
      impair cerebral or systemic hemodynamics.

PMID- 16628065
TI  - nPKCepsilon and NMDA receptors participate in neuroprotection induced by morphine
      pretreatment.
AB  - Morphine pretreatment induces ischemic tolerance in neurons, but it remains
      uncertain whether novel protein kinase C epsilon isoform (nPKCepsilon) and N
      methyl-D-aspartate (NMDA) receptors are involved in this neuroprotection. The
      present study examined this issue. Hippocampal slices from adult BALB/C mice were
      incubated with morphine at 0.1-10.0 muM in the presence or absence of various
      antagonists for 30 minutes and then kept in morphine- and antagonist-free buffer
      for 30 minutes before being subjected to oxygen-glucose deprivation for 20
      minutes. After recovery in oxygenated artificial fluid for 5 hours, assessment of
      slice injury was done by determination of the intensity of slice stain after they
      were incubated with 2% 2,3,5-triphenyltetrazolium chloride for 30 minutes and
      extracted by organic solvent for 24 hours. At designated periods, slices were
      preserved for immunoblot analysis to observe effects of morphine pretreatment on
      membrane translocation and total protein expression of nPKCepsilon and
      phosphorylation of NR1 subunits of NMDA receptors. The neuroprotection induced by
      morphine pretreatment was partially blocked by chelerythrine (a nonselective PKC
      blocker), epsilonv(1-2) (a selective nPKCepsilon antagonist), MK-801 (a
      noncompetitive NMDA receptor blocker), chelerythrine combined with MK-801, and
      epsilonv(1-2) with MK-801. Morphine pretreatment significantly inhibited
      nPKCepsilon membrane translocation and phosphorylation of NR1 subunits of NMDA
      receptors during reperfusion injury. However, epsilonv(1-2) blocked these effects
      induced by morphine pretreatment. These findings suggested that nPKCepsilon and
      NMDA receptors might participate in neuroprotection induced by morphine
      pretreatment, and NMDA receptors might be downstream targets of nPKCepsilon.

PMID- 16628066
TI  - Aging: impact upon local cerebral oxygenation and blood flow with acute
      isovolemic hemodilution.
AB  - Data from the neurosurgical critical care arena demonstrate a correlation between
      cerebral oxygenation, survival, and cognitive function. Transfusion may increase
      and hemodilution decrease cerebral oxygenation. Both acute and chronic anemia
      have been associated with cognitive dysfunction. Aggressive blood conservation
      protocols have been instituted across all age groups without conclusive evidence
      for their impact upon outcome. Aged subjects are at the greatest risk of
      cognitive sequelae after major surgery associated with significant blood loss. We
      hypothesize that cerebral physiologic changes associated with "normal" aging may
      compromise cerebral oxygenation in the presence of severe anemia.Fischer 344
      rats, the NIH National Institute of Aging normal aging rat model, underwent a
      stepwise isovolemic hemodilution protocol. Age groups (Age Grp) studied were as
      follows: Age Grp-A (3 months), n=14; Age Grp-B (9 to 12 months), n=14; and Age
      Grp-C (24 months), n=14. Brain oxygen tension (PBrO2), laser Doppler flow, and
      mean arterial pressure were measured. Final hemoglobin averaged 6.1+/-0.9 g/dL.
      PBrO2 levels decreased from a baseline of 18.1+/-4.1 to 17.5+/-6.8 mm Hg
      (P=0.49), and laser Doppler flow increased by 18+/-20% (P<0.0001) after
      hemodilution. Employing repeated measures multiple regression, Age Grp (P=0.30)
      was not a significant controlling covariate of PBrO2 in response to isovolemic
      hemodilution. PBrO2 levels were actually higher in Age Grp-C animals at all time
      points of the hemodilution protocol, although this was not statistically
      significant. Aged animals were also fully capable of mounting a robust local
      cerebral hyperemic response to the anemic challenge that was not separable from
      the response of younger animals.

PMID- 16628067
TI  - The brain erythropoietin system and its potential for therapeutic exploitation in
      brain disease.
AB  - The discovery of the broad neuroprotective potential of erythropoietin (EPO), an
      endogenous hematopoietic growth factor, has opened new therapeutic avenues in the
      treatment of brain diseases. EPO expression in the brain is induced by hypoxia.
      Practically all brain cells are capable of production and release of EPO and
      expression of its receptor. EPO exerts multifaceted protective effects on brain
      cells. It protects neuronal cells from noxious stimuli such as hypoxia, excess
      glutamate, serum deprivation or kainic acid exposure in vitro by targeting a
      variety of mechanisms and involves neuronal, glial and endothelial cell
      functions. In rodent models of ischemic stroke, EPO reduces infarct volume and
      improves functional outcome, but beneficial effects have also been observed in
      animal models of subarachnoid hemorrhage, intracerebral hemorrhage, traumatic
      brain injury, and spinal cord injury. EPO has a convenient therapeutic window
      upon ischemic stroke and favorable pharmacokinetics. Results from first
      therapeutic trials in humans are promising, but will need to be validated in
      larger trials. The safety profile and effectiveness of EPO in a wide variety of
      neurologic disease models make EPO a candidate compound for a potential first
      line therapeutic for neurologic emergencies.

PMID- 16628068
TI  - Orbital head pain elicited by neuroendoscopy of the third ventricle performed
      under local anesthesia.
AB  - Endoscopic third ventriculostomy (ETVS) is considered a minimally invasive
      procedure for blocked hydrocephalus. In 24 cases, this procedure was carried out
      in awake patients under local anesthesia. All patients reported abrupt orbital
      pain when the third ventricle floor was manipulated. Although recent advancements
      in knowledge of some forms of migraine and cluster headache could be regarded as
      a good basis for interpreting the pain triggered by ETVS, other hypotheses should
      also be taken into consideration.

PMID- 16628069
TI  - Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a
      prospective randomized pilot study.
AB  - We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4)
      infusion for aneurysmal subarachnoid hemorrhage (SAH).Sixty patients with SAH
      were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion
      for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm
      were treated with hypertensive and hypervolemic therapy. Neurologic status was
      assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome
      Scale. Incidences of cardiac and pulmonary complications were also recorded.
      Patient characteristics, severity of SAH, and surgical treatment did not differ
      between groups. The incidence of symptomatic vasospasm decreased from 43% in the
      saline group to 23% in patients receiving MgSO4 infusion, but it did not reach
      statistical significance, P=0.06. For patients who had transcranial Doppler
      detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard
      index >3, the duration was shorter in the magnesium group compared with controls
      (P<0.01). There was, however, no difference between groups in functional recovery
      or Glasgow Outcome Scale score. The incidence of adverse events such as brain
      swelling, hydrocephalus, and nosocomial infection was also similar in patients
      receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for
      aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study
      recruiting approximately 800 patients is required to test for a possible
      neuroprotective effect of magnesium after SAH.

PMID- 16628074
TI  - Pressure inside the neuroendoscope should be measured on the inflow channel.

PMID- 16628075
TI  - Measurement of table elevation of the Jackson spine table for studies involving
      the reverse Trendelenburg position.

PMID- 16628076
TI  - Cardiac asystole during radiofrequency lesioning of the trigeminal ganglion.

PMID- 16628077
TI  - Prospective and challenges of islet transplantation for the therapy of autoimmune
      diabetes.
AB  - Pancreatic islet cell transplantation is an attractive treatment of type 1
      diabetes (T1D). The success enhanced by the Edmonton protocol has fostered
      phenomenal progress in the field of clinical islet transplantation in the past 5
      years, with 1-year rates of insulin independence after transplantation near 80%.
      Long-term function of the transplanted islets, however, even under the Edmonton
      protocol, seems difficult to accomplish, with only 10% of patients maintaining
      insulin independence 5 years after transplantation. These results differ from the
      higher metabolic performance achieved by whole pancreas allotransplantation, and
      autologous islet cell transplantation, and form the basis for a limited
      applicability of islet allografts to selected adult patients. Candidate problems
      in islet allotransplantation deal with alloimmunity, autoimmunity, and the need
      for larger islet cell masses. Employment of animal islets and stem cells, as
      alternative sources of insulin production, will be considered to face the problem
      of human tissue shortage. Emerging evidence of the ability to reestablish
      endogenous insulin production in the pancreas even after the diabetic damage
      occurs envisions the exogenous supplementation of islets to patients also as a
      temporary therapeutic aid, useful to buy time toward a possible self-healing
      process of the pancreatic islets. All together, islet cell transplantation is
      moving forward.

PMID- 16628078
TI  - Influence of steroid therapy on the course of diabetes mellitus in patients with
      autoimmune pancreatitis: findings from a nationwide survey in Japan.
AB  - OBJECTIVE: The aim of this study was to estimate the number of autoimmune
      pancreatitis (AIP) patients in Japan and evaluate the influence of steroid
      therapy on the course of diabetes mellitus (DM) in AIP. METHODS: A total of 2972
      departments were randomly selected with hospital stratification throughout Japan.
      We sent a questionnaire asking the selected departments to report the number of
      patients who had visited their hospital in 2002 and who fulfilled the diagnostic
      criteria for AIP set by the Japan Pancreas Society. We then sent a second
      questionnaire asking for the details of the clinical course of DM, if any, and
      the treatments used for AIP. RESULTS: The annual number of AIP in Japan was
      estimated as approximately 900 (95% confidence interval 670-1100) or 0.71 per
      100,000 individuals in the Japanese population. In the second survey, 66.5% of
      the 167 patients of AIP were reported as being complicated with DM. Among the AIP
      patients with DM (n = 93), 52% of the patients started to show DM simultaneously
      with the onset of AIP, and 33% of the patients had DM before the onset of AIP.
      Following steroid therapy, 55% and 36% of these patient groups showed improvement
      of DM control, respectively. On the other hand, less than 20% of patients showed
      newly developed DM or showed exacerbation of DM control after steroid therapy.
      The older the patients were, the higher were the rates of new development or
      exacerbation of DM. CONCLUSIONS: These findings indicated that steroid therapy
      has a beneficial effect on the clinical courses of DM in approximately half of
      AIP patients. However, it also has negative effect on glucose tolerance in some
      patients, particularly older patients, and thus, careful observation for
      involvement of DM should be required in AIP patients treated with steroids.

PMID- 16628079
TI  - Effect of rat-to-mouse bioartificial pancreas xenotransplantation on diabetic
      renal damage and survival.
AB  - OBJECTIVE: Diabetic nephropathy is a life-threatening complication of diabetes
      mellitus. Bioartificial pancreas transplantation is becoming a therapeutic option
      for diabetes mellitus as it protects both allogeneic and xenogeneic islets from
      the host immune system. This study was undertaken to determine the effectiveness
      of bioartificial pancreas transplantation to improve or prevent diabetic renal
      damage. METHODS: Approximately 800 rat islets were macroencapsulated in polyvinyl
      alcohol gel and then transplanted into the peritoneal cavity of diabetic mice
      (transplantation group [Tx group]). Diabetic mice transplanted with a capsule
      without islets served as a sham operation group. After transplantation, the
      following data were collected: survival, body weight, blood glucose, blood urea
      nitrogen, serum creatinine levels, urinalysis, water intake, and histological
      changes in the kidney. RESULTS: There was a significant improvement in survival,
      blood glucose, blood urea nitrogen, and creatinine in the Tx group compared with
      the sham operation group. No remarkable changes were seen in urinary parameters
      between the 2 groups, and there was also no significant difference in water
      intake. Histological examination revealed that mesangial matrix expansion was
      decreased in the Tx group. CONCLUSIONS: This study demonstrated that polyvinyl
      alcohol gel bioartificial pancreas transplantation can protect the kidney from
      diabetic damage.

PMID- 16628080
TI  - Safety and preliminary clinical activity of a novel pancreatic enzyme preparation
      in pancreatic insufficient cystic fibrosis patients.
AB  - OBJECTIVES: Currently available pancreatic enzyme products are crude porcine
      products with few data available regarding their efficacy, safety, and
      manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product,
      TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase,
      protease, and amylase, to determine its safety and preliminary efficacy in cystic
      fibrosis. METHODS: We conducted an open-label, dose-ranging study in 23 subjects
      diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects
      received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per
      meal with each meal or snack for 3 days. The clinical and laboratory parameters
      and adverse events (AEs) were monitored. RESULTS: There were no serious AEs. Most
      AEs were mild, although gastrointestinal complaints were common. TCT increased
      the coefficient of fat and nitrogen absorption in all groups except in the low
      dose group. At the other dosing levels, the mean coefficient of fat and nitrogen
      absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively,
      whereas the mean stool weight decreased by 517 +/- 362 g. CONCLUSIONS: TCT was
      well tolerated in this short-term exposure study. The preliminary efficacy data
      demonstrate lipase and protease activity with little difference seen with lipase
      doses greater than 500 USP U/kg per meal. These data support a larger randomized
      phase 2 trial.

PMID- 16628082
TI  - Analysis of long-term survivors after surgical resection for pancreatic cancer.
AB  - OBJECTIVES: The purpose of this study was to determine the outcome of surgical
      resection for pancreatic cancer and to characterize the clinicopathologic
      features of actual long-term survivors. METHODS: Of the 789 pancreatic cancer
      patients, we retrospectively analyzed 242 patients who underwent an operation
      between 1985 and 1999. Surgical resection with curative intent was performed in
      123 patients. We analyzed the overall results of surgical treatment, compared the
      clinicopathologic features between long-term and short-term survivors, and
      reevaluated the histological slides of the long-term survivors. RESULTS: Median
      survival and cumulative 5-year survival rate after surgical resection were 14.8
      months and 12.1%. Tumor size, American Joint Committee on Cancer stage, resection
      margin involvement, and lymph node metastases were the significant prognostic
      factors. Eleven patients survived for more than 5 years. Some patients with poor
      prognostic factors such as lymph node metastasis and big tumor size survived for
      more than 5 years. Histological reevaluation in the long-term survivors revealed
      4 cases of variant adenocarcinoma (anaplastic carcinoma, mucinous noncystic
      adenocarcinoma [n = 2], and undifferentiated carcinoma). CONCLUSIONS: Active
      surgical resection should be attempted even in patients with poor prognostic
      factors. As there were various types of pathology among the long-term survivors,
      typical ductal adenocarcinoma of the pancreas might have a poorer survival rate.

PMID- 16628081
TI  - Clinical significance of serum thioredoxin 1 levels in patients with acute
      pancreatitis.
AB  - OBJECTIVE: Thioredoxin 1 (TRX-1), a redox-regulating protein with antioxidant
      activity, is induced by oxidative stress, and serum TRX-1 levels are recognized
      as an oxidative-stress marker. The aim of this study was to clarify the clinical
      significance of serum TRX-1 levels in patients with acute pancreatitis (AP) and
      evaluate the usefulness of this measurement in assessing disease severity.
      METHODS: Serum TRX-1 levels were determined on admission in 18 patients with
      severe AP and 36 patients with mild AP. We also investigated the relationship
      between serum TRX-1 levels and clinical and laboratory data. RESULTS: The median
      serum TRX-1 levels on admission were 54.9 ng/mL in mild AP and 118.8 ng/mL in
      severe AP. When the cutoff value for TRX-1 in predicting severe AP was determined
      to be 100 ng/mL, its sensitivity, specificity, and accuracy were 83.3%, 94.4%,
      and 90.7%, respectively. A significant correlation was observed between serum TRX
      1 levels and Ranson score (r = 0.674), C-reactive protein (r = 0.718),
      interleukin 6 (r = 0.712), leukocyte count (r = 0.642), and serum amylase (r =
      0.436). CONCLUSIONS: Serum TRX-1 levels significantly correlate with AP severity.
      TRX-1 should constitute a reliable oxidative-stress marker for the evaluation of
      AP severity in relation to oxidative stress.

PMID- 16628083
TI  - Solid pseudopapillary tumor of the pancreas suggesting malignant potential.
AB  - OBJECTIVES: It has been suggested that the histopathologic features associated
      with malignant potential in solid pseudopapillary tumors (SPTs) of the pancreas
      include cellular polymorphism, mitotic activity, peripancreatic tissue invasion,
      neural invasion, lymphovascular invasion, and lymph node metastasis. This study
      aimed to delineate the features predicting SPTs with malignant potential, which
      can be easily assessed in the clinical setting, and long-term results of patients
      who underwent resection of SPT. METHODS: A retrospective review and analysis were
      done of 33 patients who had SPTs that were surgically treated. RESULTS: Eleven
      patients (33.3%) had SPTs suggesting malignant potential among surgically treated
      patients with SPTs. The local invasion to the peripancreatic tissue was the most
      frequent malignant pathological feature (7/11 patients, 63.7%). Using univariate
      analysis, tumor size greater than 5 cm was a significant clinical factor to
      predict SPTs with malignant potential (P = 0.022). The prognosis was excellent.
      No statistically significant survival difference was noted between groups of
      malignant potential and benign pathology (P = 0.1904). CONCLUSIONS: Malignant
      SPTs are low-grade tumors with good prognosis. Adequate surgical intervention is
      necessary. Especially, SPTs over 5 cm in diameter need to be treated carefully
      because of the chance of malignant pathology. Careful long-term follow-up is
      necessary in those patients in case of possible tumor recurrences.

PMID- 16628084
TI  - Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of
      the pancreas: a clinicopathologic comparison with a common type of invasive
      ductal carcinoma.
AB  - OBJECTIVES: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an
      indolent neoplasm by nature; however, it sometimes acquires invasive potential
      and has been classified as invasive IPMN. The aim of the present study was to
      investigate the clinicopathologic difference between invasive IPMN and a common
      type of invasive ductal carcinoma of the pancreas. METHODS: Eighteen patients
      with invasive IPMN underwent pancreatectomy between 1992 and 2004. Clinical,
      biochemical, and histopathologic factors were retrospectively analyzed. The
      resulting data were compared with those of 274 patients with a common type of
      pancreatic ductal carcinoma who underwent surgery during the same period.
      RESULTS: The total size of tumor of invasive IPMN, including cystic and invasive
      components, was statistically larger than that of a common type of invasive
      ductal carcinoma (62 vs 40 mm, P < 0.001), but the size of invasive component of
      invasive IPMN was smaller than that of a common type of invasive ductal carcinoma
      (21 vs 40 mm, P < 0.001). Negative lymph node metastases and relatively limited
      local tumor spreading were frequently observed in patients with invasive IPMN. On
      microscopic examination, the tumors infiltrating the surrounding tissue had a
      less invasive growth pattern, and a lower frequency of lymphatic invasion, venous
      invasion, and intrapancreatic neural invasion was also observed in patients with
      invasive IPMN. The 5-year survival rate of invasive IPMN was significantly higher
      than that of common-type invasive ductal carcinoma (42% vs 20%, P = 0.04).
      CONCLUSIONS: An increased awareness of invasive IPMN has enabled pancreatectomies
      to be performed at an earlier stage, relative to that for ordinary pancreatic
      cancer. The less frequent detection of pathological factors concerned with tumor
      invasiveness in patients with invasive IPMN suggested the lower aggressive
      behavior of this tumor.

PMID- 16628085
TI  - XIAP is related to the chemoresistance and inhibited its expression by RNA
      interference sensitize pancreatic carcinoma cells to chemotherapeutics.
AB  - OBJECTIVES: To explore the exact role does the x-linked inhibitor of apoptosis
      (XIAP) play in chemoresistance of pancreatic carcinoma cell and the cell
      sensitivity to chemotherapeutic drugs changed after XIAP is inhibited by RNA
      interference (RNAi). METHODS: Pancreatic carcinoma cell line SW1990 was exposed
      to 5-fluorouracil (5-fu) with the concentrations of 1.0 and 10 mug/mL to increase
      the expression of XIAP. Then 4 RNAi plasmid vectors against XIAP were designed
      and constructed, then transfected into SW1990. Repressive effect was evaluated by
      reverse transcriptase polymerase chain reaction and Western blot; 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry were
      performed to determine cell sensitivity to 5-fu and gemcitabine; furthermore,
      apoptosis is confirmed by Hoechst 33258 stain. RESULTS: XIAP of SW1990 can be up
      regulated with the chemoresistance increasing 1.5- and 4-fold after 10 and 30
      days induced by 5-fu. Two of the 4 vectors can inhibit the expression of XIAP
      protein more than 60%. The cells apoptosis index induced by 5-fu and gemcitabine
      increased greatly after XIAP is inhibited by the RNAi plasmid vectors.
      CONCLUSIONS: XIAP is one of the most important factors in the pancreatic
      carcinoma chemoresistance, and inhibition of XIAP in pancreatic carcinoma can
      enhance the cancer sensitivity to chemotherapeutic drugs.

PMID- 16628086
TI  - Effect of antisense hypoxia-inducible factor 1alpha on progression, metastasis,
      and chemosensitivity of pancreatic cancer.
AB  - OBJECTIVES: The aim of the study was to observe the effect of antisense hypoxia
      inducible factor 1alpha (HIF-1alpha) on progression, metastasis, and
      chemosensitivity of pancreatic cancer. METHODS: BxPc-3 cells transfected with
      antisense HIF-1alpha plasmid were exposed to 0.5% O2 for 4 hours. Expressions of
      HIF-1alpha, survivin, and beta1 integrin were detected by reverse transcriptase 
      polymerase chain reaction and Western blotting. Growth inhibition rates and
      apoptosis rates of BxPc-3 cells under different dosages of chemotherapy agents (5
      fluorouracil, doxorubicin, and gemcitabine) were measured by MTT colorimetric
      assay and flow cytometry. The migration of BxPc-3 cells was assayed using
      transwell cell culture chambers. Subcutaneous transplantation of BxPc-3 cells in
      nude mice for 8 weeks was to assess progression and metastasis of pancreatic
      cancer. RESULTS: Expression of HIF-1alpha was obviously down-regulated, and at
      the same time, survivin and beta1-integrin expressions were markedly down
      regulated in the experimental group (P < 0.05). Higher dosages (100, 200, and 400
      mg/L of 5-fluorouracil; 0.05, 0.075, and 0.1 mg/L of doxorubicin; and 10(-9), 10(
      8), and 10(-7) mol/L of gemcitabine) caused a greater increase of inhibition in
      the experimental group than in control (P < 0.05). The number of migrated BxPc-3
      cells in the experimental group was far less than in control (P < 0.05). In vivo,
      the tumor size and weight in the experimental group were significantly lower than
      those in control (P < 0.05). CONCLUSION: Our data demonstrate that antisense HIF
      1alpha inhibits expressions of survivin and beta1 integrin, enhancing apoptosis
      in human pancreatic cancer cells and restraining the progression and metastasis
      of pancreatic cancer. Therefore, HIF-1alpha may play a very important role in
      progression, metastasis, and chemosensitivity of human pancreatic cancer.
      Blocking HIF-1alpha in pancreatic cancer cells may offer an avenue for gene
      therapy.

PMID- 16628087
TI  - Sequence variation outside the "active" region of dog and rabbit cholecystokinin
      58 results in bioactivity differences.
AB  - OBJECTIVES: We propose that regions outside the bioactive 7-amino acid carboxyl
      terminus of cholecystokinin (CCK)-58 influence its biological activity. Here we
      evaluate if sequence variation of the N-terminal regions of rabbit and canine CCK
      58 changes their biological activities. METHODS: Cholecystokinin-like
      immunoreactivity was purified from rabbit intestinal extracts by reverse phase
      and ion-exchange high-performance liquid chromatography steps. The peptide was
      characterized by microsequence and mass spectral characterizations of the intact
      and tryptic peptides. Canine and rabbit CCK-58 were evaluated for their CCK1 and
      CCK2 receptor binding, receptor activation, and immunologic properties. RESULTS:
      The sequence of rabbit CCK-58 differs from that of canine CCK-58 in 9 of the
      amino terminal 40 residues. Canine CCK-58 was approximately 3-fold more potent
      than rabbit CCK-58 for CCK1 receptor binding and CCK2 receptor binding, but about
      the same potency for stimulation of amylase release from purified acinar cells.
      The canine peptide was 9-fold more immunoreactive than rabbit CCK-58.
      CONCLUSIONS: Canine and rabbit CCK-58 have different biological and immunologic
      properties that can only result from differences in their N-terminal sequences
      which influence the properties of their identical carboxyl termini. These results
      are the first direct demonstration that amino acids outside the C-terminus of CCK
      58 influence CCK biological activity.

PMID- 16628088
TI  - Calcineurin-dependent and calcineurin-independent signal transduction pathways
      activated as part of pancreatic growth.
AB  - OBJECTIVE: We have recently reported that pancreatic growth driven by
      cholecystokinin released endogenously by feeding the synthetic trypsin inhibitor
      camostat requires the Ca-activated phosphatase calcineurin. In the present study,
      we evaluated a number of signal transduction pathways for their activation as
      part of the growth response and whether their activation was dependent on
      calcineurin. METHODS: Male ICR mice were fed with either chow or chow plus 1 mg/g
      of camostat. FK506 was administered at 3 mg/kg. After various times from 12 hours
      to 10 days, pancreatic samples were prepared and assayed for activity of various
      signal transduction pathway components. RESULTS: Camostat feeding increased the
      activation of extracellular signal-regulated kinases, c-Jun NH2-terminal kinases,
      and phosphorylation of the translation factor eukaryotic initiation factor 4E and
      activated the mammalian target of rapamycin pathway that leads to phosphorylation
      of the ribosomal protein S6 and of the eukaryotic initiation factor 4E binding
      protein but with different time courses. Treatment of mice with the calcineurin
      inhibitor FK506 totally blocked c-Jun NH2-terminal kinase activation, partially
      blocked the mammalian target of rapamycin pathway, and had no effect on
      extracellular signal-regulated kinase activation or the phosphorylation of
      eukaryotic initiation factor 4E. CONCLUSIONS: The pancreatic growth response is
      accompanied by activation of a number of signaling pathways regulating
      transcription and translation, some of which are dependent on and some
      independent of calcineurin.

PMID- 16628089
TI  - Recurrent invasive intraductal papillary mucinous carcinoma of the pancreas
      mimicking pott disease: review of the literature.
AB  - Specific information regarding intraductal papillary mucinous neoplasm (IPMN)
      recurrence is limited because most series are small and the follow-up interval is
      short. We report an unusual case of cancer recurrence in an 86-year-old woman who
      had undergone a pancreaticoduodenectomy for a large IPMN in the head of the
      pancreas. Final pathological evaluation of the resected pancreas found a
      component of in situ and invasive ductal adenocarcinoma without lymph node
      involvement. The patient did not receive postoperative chemotherapy and was
      monitored with transaxial imaging at regular intervals. Nine years later, the
      patient developed a retroperitoneal psoas abscess that was misdiagnosed as
      tuberculous spondylitis (Pott disease) but was proven to be recurrent mucinous
      adenocarcinoma of pancreatic origin. In our review of published reports in
      patients who underwent resection of IPMN, we found a combined mean recurrence
      rate of approximately 20%.

PMID- 16628090
TI  - Immunohistochemical and genetic analysis of osteoclastic giant cell tumor of the
      pancreas.
AB  - Clinical, histopathologic, immunohistochemical, and genetic analyses of 2
      osteoclastic giant cell tumors of the pancreas are presented. The neoplasms were
      composed of osteoclastic giant cells and pleomorphic cells (PCs). The tissue
      specific markers gave evidence of mesenchymal nature of the osteoclastic giant
      cells, as well as other components of the tumor, and lacked any signs of
      epithelial differentiation in both patients. The nonepithelial nature of both
      components in the osteoclastic giant cell tumors presented may be associated with
      a better prognosis, which corresponds to the previous reports of similar
      neoplasms. A positive immunoreactivity to neuron-specific enolase was recorded in
      patient 2. The presence of CD68 in osteoclastic giant cells proved their
      histiocytic nature. Both components of the tumors showed a negative
      immunoreactivity to desmin and only a scattered reactivity to smooth muscle cell
      actin, typical markers of myofibroblastic differentiation. Mutation analysis of
      the tumor revealed the wild state of both p53 and K-ras oncogenes in both
      patients. A positive immunoreactivity for p53 in PCs of both osteoclastic giant
      cell tumors was recorded, whereas osteoclastic giant cells did not express this
      protein. The expression of p21 was recorded in osteoclastic giant cells in
      patient 1. The absence of Ki-67 in the osteoclastic giant cells and its
      expression in PCs gave evidence of a different proliferation rate of both cell
      populations. Different tissue-specific markers, a different proliferation rate,
      and a different state of oncogene activation in the osteoclastic giant cell
      tumors contribute to the idea that the tumor derives from a pluripotent cell that
      may differentiate into an array of phenotypes.

PMID- 16628091
TI  - Pankrin: a new parameter for the diagnosis of acute pancreatitis in cases of late
      clinical presentation.

PMID- 16628092
TI  - Colonic apple-core lesion resulting from cyberknife treatment of unresectable
      pancreatic cancer.

PMID- 16628093
TI  - Imaging features of large intraductal papillary mucinous carcinoma of the
      pancreatic tail.

PMID- 16628094
TI  - Impact of rapid influenza testing at triage on management of febrile infants and
      young children.
AB  - OBJECTIVE: To determine the impact of an emergency department (ED) triage
      protocol for rapid influenza testing of febrile infants and children on
      additional diagnostic testing, ED charges and patient time in the ED. METHODS: A
      trial of triage-based rapid influenza A and B testing of febrile infants and
      children 3 to 36 months of age presenting to an urban ED during December 2002 to
      March 2003 was performed. Children with a temperature of 39 degrees C or higher
      or history of fever 102 degrees F or higher at home were included. Those with
      obvious focal infection, potential immunodeficiency, and indwelling medical
      devices were excluded. The intervention group, tested for influenza at triage
      (TT) was compared with a nonintervention group consisting of those receiving
      usual care (SP). A subanalysis comparing influenza-positive children was
      performed. RESULTS: Of 1007 eligible subjects a total of 719 (71%) patients were
      in the SP group and 288 in the TT group. There were significant differences in
      respiratory syncytial virus rapid test (RSV; 18%-7%) and chest radiographs (CXRs;
      26%-20%) tests in the TT group. In addition, significant increases in obtaining a
      complete blood count (relative risk [RR] 12.0; 95% confidence interval [CI] 2.9
      49), blood culture (RR, 12.0; 95% CI, 3.0-51.0), RSV testing (RR, 0.9.2; 95% CI,
      3.4-25.0), urinalysis (RR, 5.7; 95% CI, 2.0-16.0), CXR (RR, 2.2; 95% CI, 1.04
      4.5), time in the ED (195 vs 156 minutes; 95% CI, of the difference 19-60), and
      medical charges ($666 vs $393; 95% CI, of the difference 153-392) were seen among
      those testing positive for influenza in the SP group. CONCLUSIONS: A triage
      protocol for rapid influenza testing for febrile infants and children appears to
      significantly decrease additional testing, time in the ED, and charges in
      children testing positive for influenza.

PMID- 16628095
TI  - Health care providers' opinions on intimate partner violence resources and
      screening in a pediatric emergency department.
AB  - OBJECTIVES: The American Academy of Pediatrics has called upon pediatricians to
      routinely screen for intimate partner violence (IPV) as an active means by which
      to prevent child abuse. The pediatric emergency department (ED) is one
      potentially important site to screen and to provide women with IPV resources.
      This cross-sectional questionnaire investigated pediatric health care providers'
      (HCPs') opinions about displaying IPV posters and performing IPV screening in a
      pediatric ED. METHODS: This cross-sectional survey was conducted in the ED of an
      urban, academic, tertiary care children's hospital that serves approximately
      70,000 children each year. A convenience sample of 151 HCPs, defined as any
      person who provided medical care, including physicians, nurses, paramedics, and
      respiratory therapists, in the pediatric ED was surveyed using a 4-item
      questionnaire, designed by investigators, about their views regarding newly
      displayed IPV posters and resource cards, their opinions about universal IPV
      screening, and their personal use of the IPV materials. Between June and August
      2004, surveys were distributed, along with return envelopes to be placed in a
      sealed box, to HCPs during their shifts in the ED. RESULTS: Of the 158
      distributed surveys, 151 (96%) were returned. Of the sample, 30% were physicians,
      53% were RNs, 10% were paramedics/emergency medical technicians, and 7% were
      other HCPs. Pediatric ED providers supported both IPV resource information and
      routine screening. Female providers were more likely than men to support the IPV
      posters. Five percent of the sample took IPV resource information for themselves
      or for later use with patients. CONCLUSIONS: Our pediatric ED's providers'
      endorsement of IPV screening and of the presence of IPV posters demonstrates
      support for and recognition of the problem of IPV in their patients' families.

PMID- 16628096
TI  - Psychosocial needs of African American youth presenting to a pediatric emergency
      department with assault-related injuries.
AB  - OBJECTIVE: The purpose of this study was to identify the psychosocial needs
      confronting African American youth assaulted in their community. METHODS: A
      convenience sample of 36 African American youth (mean age, 14.8 years; range, 10
      18 years) who presented to a pediatric emergency department with violent
      interpersonal injuries was interviewed to identify the psychosocial issues they
      were facing. Participants also completed self-report measures of violence
      exposure and trauma symptoms, and their parents completed a screening measure of
      the youths' emotional and behavioral functioning. RESULTS: During the interview,
      the youth reported 178 different concerns that were content-analyzed and placed
      into 10 thematic categories labeled anger/aggressive behavior (78% of
      respondents), general internalizing symptoms (61%), peer difficulties (53%),
      parent/family conflict (50%), posttraumatic stress symptoms (47%), academic
      concerns (42%), physical health concerns (39%), safety concerns (39%), and public
      service concerns (17%). Elevated rates of historical violence exposure and trauma
      symptoms were observed on the self-report measures, and one third of the youths'
      parents reported levels of emotional and behavioral problems that would warrant
      further clinical attention. CONCLUSION: African American assault victims are
      experiencing a broad range of psychosocial needs. To bolster youth recovery and
      reduce the risk of future injury, researchers and practitioners need to identify
      effective methods of assessing these needs in the emergency department so that
      youth victims of interpersonal violence can be referred for appropriate follow-up
      services.

PMID- 16628097
TI  - Epidemiology of exercise equipment-related injuries to young children.
AB  - OBJECTIVES: The objective of this study was to describe and identify the type,
      cause, and epidemiology of injuries related to exercise equipment to children
      younger than 5 years reported to US emergency rooms. METHODS: A retrospective
      review of data for children 4 years old and younger from the National Electronic
      Injury Surveillance System of the US Consumer Product Safety Commission for the
      years 1994 to 2001 was conducted. A total of 1679 children were identified
      obtaining treatment at a participating emergency room. RESULTS: There were an
      estimated 46,440 exercise equipment-related injuries (95% confidence interval,
      38,081-55,079 injuries) to children 4 years old and younger treated in hospital
      emergency departments in the United States during the 8-year study period. The
      annual rate of injury among children was 28.32 per 100,000. Most injuries
      involved the head, foot, and hand regions. Injury diagnosis included lacerations
      (49%), soft tissue injuries (29%), and fractures and dislocations (9%). Most
      hospital admissions were for amputations (36%), fractures (34%), and lacerations
      (20%). CONCLUSIONS: Injuries can result from children's exposure to exercise
      equipment in the home. Parental awareness of the dangers of home-based exercise
      equipment and the potential hazards of exercise equipment-related injuries on the
      limbs and head region is recommended.

PMID- 16628098
TI  - Nonparticipant injuries associated with skating activities.
AB  - OBJECTIVE: Children are at risk for injury even if they are not active
      recreational participants. This study describes the epidemiology of pediatric
      nonparticipant skating-related injuries treated in hospital emergency departments
      in the United States from 1993 to 2003. METHODS: Narratives of injuries
      identified by the US Consumer Product Safety Commission's National Electronic
      Injury Surveillance System consumer product codes as ice-skating, roller-skating,
      and in-line skating-related were reviewed. RESULTS: Fifty-eight children were
      treated for nonparticipant skating-related injuries in National Electronic Injury
      Surveillance System emergency departments. Mechanisms of injury included being
      stepped on (36.2%), dropped (34.5%), or kicked (12.1%) by skaters and collision
      with skaters (17.2%). The most common body regions injured were the lower
      extremities (41.4%), upper extremities (24.1%), and head (20.7%).
      Contusions/abrasions (32.8%), lacerations (20.7%), and fractures (19.0%) were the
      most common diagnoses. Children who were dropped sustained more head injuries
      than children injured by other mechanisms (relative risk [RR], 20.9; 95%
      confidence interval [CI], 2.9-150.5; P < 0.001) and were younger than those
      stepped on (RR, 1.5; 95% CI, 1.1-2.2; P = 0.02) or kicked (RR, 6.7; 95% CI, 1.1
      40.9; P < 0.001). Children stepped on by skaters experienced more injuries to the
      extremities than children who were dropped by (RR, 3.3; 95% CI, 1.7-6.5; P <
      0.001) or collided with skaters (RR, 1.7; 95% CI, 1.0-2.8; P < 0.01).
      CONCLUSIONS: Children are at risk for injury when they are around skaters. The
      risk of such injuries can be reduced if children are never carried by skaters,
      young children are closely supervised to avoid collisions, and skaters are
      cautioned against kicking or stepping on other children.

PMID- 16628099
TI  - Danger of flumazenil use in pediatric status epilepticus.
AB  - Benzodiazepines are an important class of drugs in the management of acute
      pediatric seizure disorders such as status epilepticus. They are used both in the
      community and in the hospital; however, one of their major side effects is
      respiratory depression. If ventilation is needed for benzodiazepine-induced
      respiratory depression during seizure management, pressures to facilitate
      extubation may lead to the use of the specific reversal agent for this class of
      drugs, flumazenil. Three cases of seizure recurrence after flumazenil use in this
      context are reported, and the pharmacology is discussed. Irrespective of pressure
      to extubate such children, physicians must be alert to the potential risk of
      flumazenil in the clinical scenario.

PMID- 16628100
TI  - An infant with trisomy 21 and tachypnea.
AB  - A 4-month-old infant with trisomy 21 is brought to the emergency department for
      breathing difficulty. Subsequently, he is diagnosed with a Morgagni diaphragmatic
      hernia. Tachypnea in an infant with trisomy 21 may be the result of diagnosis
      such as congenital heart disease, infectious processes, structural anomalies, or
      aspiration secondary to gastroesophageal reflux or swallowing dysfunction.
      Knowledge of these abnormalities is important when generating a differential
      diagnosis in these patients. Although uncommon, a Morgagni hernia may present
      beyond the newborn period and should be considered when evaluating an infant with
      trisomy 21 and respiratory difficulty.

PMID- 16628101
TI  - An unusual method for the removal of a foreign body from a child's airway.
AB  - This is a case of a 6-year-old child who had a laryngeal foreign body, which was
      obstructing his airway. The object was large and dense, and traditional methods
      of removal had failed. After lifting the child upside down by his feet, the heavy
      foreign body was removed using a laryngoscope and finger sweep. Foreign body
      removal can be challenging, and this is a simple method that a practitioner may
      be able to use in a difficult case.

PMID- 16628102
TI  - Dilated cardiomyopathy and adipic aciduria in nutritional rickets.
AB  - Hypocalcemia secondary to nutritional rickets is a rare cause of dilated
      cardiomyopathy. It is also not a recognized cause of dicarboxylic aciduria. We
      report the first case of adipic aciduria, presenting with dilated cardiomyopathy,
      secondary to hypocalcemia.

PMID- 16628103
TI  - Amanita bisporigera ingestion: mistaken identity, dose-related toxicity, and
      improvement despite severe hepatotoxicity.
AB  - Ingestion of wild mushrooms has led to unintentional poisonings caused by
      mistaken identity. We report 3 cases of exposure to Amanita bisporigera,
      demonstrating dose-related toxicity. The use of nasobiliary drainage as a novel
      approach to interrupting the enterohepatic circulation of amatoxins is
      illustrated. Pathophysiology and treatment of Amanita poisoning are reviewed.

PMID- 16628104
TI  - Infant mandibular fractures: are you considering child abuse?
AB  - Mandibular fractures in infants are rare and difficult to detect. Causes include
      motor vehicle accidents, falls, and physical abuse. Historical, physical, and
      imaging aids to diagnose mandibular fractures and to differentiate abuse from
      accident are discussed. Three-dimensional computed tomographic scans are the
      preferred method of imaging. In addition, a thorough workup for physical abuse is
      needed.

PMID- 16628105
TI  - Challenges of electronic medical record implementation in the emergency
      department.
AB  - TARGET AUDIENCE: Physicians, nurse practitioners and physician assistants who
      care for infants and children in the emergency department or in other ambulatory
      and acute care settings. In particular, physicians with administrative
      responsibilities will find this information useful. OBJECTIVES: 1. Describe the
      purpose and scope of an electronic medical record. 2. Point out the unique
      demands that the emergency department places upon an EMR. 3. List the advantages
      and disadvantages of computerized charting.

PMID- 16628107
TI  - Obvious head injury: analyzing the mechanism.

PMID- 16628108
TI  - A tale of two sisters.

PMID- 16628109
TI  - Pediatric emergency medicine: legal briefs.

PMID- 16628110
TI  - ECGs in the ED.

PMID- 16628111
TI  - A 21-month-old boy with fever and red eye.

PMID- 16628113
TI  - T-Pin for distal radius fracture.
AB  - Distal radius fractures are among the most common fractures treated by orthopedic
      surgeons. Numerous techniques have been devised to address these fractures and
      the factors associated with these injuries. The T-Pin (Union Surgical, LLC,
      Philadelphia, PA) is a novel instrumentation designed to use standard
      percutaneous techniques in the treatment of extra-articular distal radius
      fractures. The T-Pin allows for early active range of motion, as well as earlier
      return to functional activities. This article discusses the instrumentation, the
      techniques of insertion and extraction, and postoperative care.

PMID- 16628114
TI  - Arthroscopic assessment and classification of Kienbock's disease.
AB  - The authors have utilised arthroscopy to assess and classify Kienbock's avascular
      necrosis of the lunate. The classification is based on the number of articular
      surfaces of the lunate and adjacent articulation, which are non-functional.
      Kienbock's disease usually affects the proximal surface of the lunate first with
      subsequent secondary changes to the lunate facet of the radius. Advanced cases
      and those with a coronal fracture of the lunate will cause involvement of the mid
      carpal joint. Surgery is aimed to debride the joint, classify the level of
      disease and direct the definitive procedure to be performed. If the articular
      surfaces are intact, a synovectomy or radial shortening would be indicated. If
      there is involvement of the lunate but an intact lunate facet a proximal row
      carpectomy would be indicated. If there is involvement of the proximal lunate and
      lunate facet then a radio-scapholunate fusion could be utilised. More extensive
      involvement of the joint would require a wrist fusion. Arthroscopy provides a
      valuable assessment and subsequent classification of Kienbock's disease.

PMID- 16628115
TI  - ARM: a modular hinged joint for the AO tubular external fixator.
AB  - Certain complex traumatic elbow lesions challenge the orthopaedic and trauma
      surgeon. If they are not treated correctly, they cause a high rate of disability,
      arising from elbow instablility and stiffness, either by fibrosis or joint
      incongruity. Injuries such as complex fractures of the proximal third of the
      ulna, coronoid fractures associated with radial head fractures (the "terrible
      triad"), are even worse if they are accompanied by soft tissue lesions. Hinged
      external fixators, complemented by other surgical procedures, are, for many, a
      recommended alternative when dealing with irreparable lesions. The AO tubular
      external fixator, by virtue of its versatility, is a very important tool in
      orthopaedics and trauma, but there is not the possibility of using it as a hinged
      fixator. The authors describe a prototype of a hinged joint that can be applied
      easily to the AO tubular external fixator, converting it into a hinged one. This
      hinged joint, in conjunction with the AO tubular external fixator, has been
      applied in 5 patients; 2 "terrible triads", one posterior elbow fracture
      dislocation with radial head fracture, one Monteggia fracture-dislocation and an
      anterior elbow dislocation that developed a forearm compartment syndrome. The
      patients' age range was between 20 and 72 years (median 45,6); 4 were male and 1
      female. In 3 patients, either a type III coronoid fracture or a radial head
      fracture, could not be repaired. One radial head was totally removed and another
      one partially removed. The remaining indications were because of severe soft
      tissue lesions. Results were evaluated using the Mayo Elbow Score Scale and the
      Broberg and Morrey radiographic evaluation scale. The median follow up was 18
      months(range 6 to 48 months). All 5 patients got a maximum score of 100 points in
      the Mayo's Elbow Score Scale, indicating excellent results. No patient suffered
      elbow pain, or any type of elbow instability. The median range of motion in
      flexion was of 127.5 degrees (max. 140 degrees and min. 120 degrees ) and the
      median extension loss was 20 degrees (max. 25 degrees and min. 15 degrees ). One
      patient had pronation limited to 70 degrees and one had supination limited to 70
      degrees . Every patient was able to resume a normal daily life activity and
      returned to normal work. In 3 patients the radiographic evaluation was Grade 0
      and in the other 2, Grade I. Two complications occurred, one was a distal ulnar
      Schanz screw loosening with osteolysis and the other was a superficial infection
      of one Schanz screw. It can be concluded that good results can be obtained in
      injuries with severe elbow instability and soft tissue lesions, using this hinged
      external fixator. With this new clamp, the AO tubular external fixator is
      transformed into a hinged one and a new use is added to this already very
      versatile system. This clamp is very easy to apply.

PMID- 16628116
TI  - Extra-articular arthrodesis of the carpometacarpal joint of the thumb.
AB  - There are numerous surgical treatment options for instability and painful
      trapeziometacarpal arthrosis. The available surgical treatments are arthrodesis
      and trapeziectomy alone or with synthetic/biologic interpositions, osteotomy, and
      total joint replacement. However, there is no clear consensus regarding the
      appropriate surgical procedure, and a unique situation exists in which the
      surgeon can develop a successful hybrid technique based on his own philosophy and
      experience. Traditionally, ligament reconstruction and tendon interposition have
      been used for elderly patients with lower demands whereas arthrodesis has been
      reserved for the treatment of posttraumatic arthritis in high-demand, younger
      patients. Regarding the second case, when thumb carpometacarpal arthrodesis is
      indicated, the procedure provides a reliable and lasting treatment with
      satisfactory results. However, it is important to know the indications and
      contraindications, as well as benefits and risks of this procedure. Therefore,
      the surgical technique is straightforward, and fusion may be performed with
      either a plate-and-screw construct, power staples, tension band wiring with or
      without Kirschner wires, or alone with multiple Kirschner wires. However, in all
      the techniques, it is necessary to remove the articular surfaces of the
      metacarpal and trapezium apart from the need of autogenous bone graft to fill the
      defect between those bones from either the distal radius or iliac crest. In
      addition, later in almost all the cases, it is necessary to remove the metal work
      because of protrusion or skin intolerance. The technique described in this
      article is a modification of a sliding inlay metacarpal bone graft technique
      originally described by Muller in 1949 and, 52 years after, perfected by Doyle.
      However, and as opposed to these, with the extra-articular arthrodesis technique,
      it is not necessary to remove the articular surfaces, and the graft fixation is
      performed by 2 Herbert screws which, when buried into the bone, avoid the need to
      remove the metal work because of the protrusion under the skin. Therefore, this
      intervention easily permits to convert the arthrodesis to another method of
      treatment (implant arthroplasty or tendon interposition arthroplasty) by means of
      the resection of the bone bridge between the metacarpal and trapezium and proceed
      to the chosen surgical intervention.

PMID- 16628117
TI  - Volar open reduction of complex metacarpophalangeal dislocation of the index
      finger: a pictorial essay.
AB  - Dislocations of the metacarpophalangeal joint are uncommon and usually caused by
      significant trauma. The distinction between subluxations and dislocations is
      critical. Complex dislocations require surgical reduction. The need for surgical
      reduction is primarily due to the anatomy of this region, which contributes to
      the complexity of this injury and to the degree of difficulty in its reduction.
      This pictorial essay aims to highlight the clinical, radiographic, and surgical
      features of this uncommon yet complex injury.

PMID- 16628118
TI  - Uses and abuses of wrist arthroscopy.
AB  - PURPOSE OF REVIEW: The use of wrist arthroscopy in the diagnosis and treatment of
      carpal pathology continues to expand. The purpose of this paper is to summarize
      recent advances in the utility of this diagnostic, therapeutic, and research
      tool. RECENT FINDINGS: The indications for wrist arthroscopy are growing with the
      description of volar portals for the radiocarpal and scaphotrapezial trapezoid
      joint. Arthroscopic assistance in the treatment of distal radius and scaphoid
      fractures is also becoming more feasible. Arthroscopic excision of dorsal carpal
      ganglions has met with considerable success. In addition, the application of
      electrothermal collagen shrinkage is an exciting new frontier in arthroscopic
      wrist procedures. SUMMARY: Wrist arthroscopy has evolved to be an essential
      diagnostic and therapeutic tool in the armamentarium of every surgeon treating
      disorders of the wrist.

PMID- 16628119
TI  - Thumb arthrodesis.
AB  - PURPOSE OF REVIEW: Arthrodesis of the thumb carpometacarpal, metacarpophalangeal,
      and interphalangeal joints are well-established options in the management of
      arthritis, instability, and/or deformity. This review includes a general review
      of the indications and technique of arthrodesis and recent review of the
      literature. RECENT FINDINGS: New literature has focused on the role of
      arthrodesis in managing carpometacarpal arthritis and compared its results with
      ligament reconstruction and tendon interposition. However, no conclusive evidence
      demonstrates the superiority of arthrodesis. Several new articles have
      demonstrated good long-term results of carpometacarpal arthrodesis. A new report
      on complications associated with plate and screw fixation for carpometacarpal
      arthritis has been published, leading the authors to conclude that k-wire
      fixation was a better option. A technique of metacarpophalangeal joint
      arthrodesis using a cannulated screw has been recently published with good
      success. Moreover, a cup-in-cone technique of reaming surfaces of the thumb
      metacarpophalangeal joint to maximize bone contact surface area has been
      described. Other authors have reiterated and reinforced the success of some of
      the more standard techniques including Herbert screws for interphalangeal joint
      arthrodeses. SUMMARY: Thumb arthrodesis of the carpometacarpal,
      metacarpophalangeal, and interphalangeal joints maintains a significant role in
      the management of deformity and arthritis. Better comparison studies are
      necessary in evaluating arthrodesis of the carpometacarpal joint versus
      arthroplasty. New fixation techniques for metacarpophalangeal joint arthrodesis
      are promising. Standard fixation for interphalangeal joint fusion has been
      reiterated. Successful arthrodesis can lead to excellent patient outcomes and
      function.

PMID- 16628120
TI  - Ulna oblique osteotomy for radius and ulna length inequality: technique and
      applications.
AB  - An ulna that is too long or too short may be responsible for symptoms around the
      wrist. Several techniques are available to shorten or lengthen the ulna. We have
      used, among other techniques, an oblique osteotomy which allows the length of the
      ulna to be modified by sliding the 2 fragments over each other, taking care to
      keep good contact between them. The main advantage of this technique is that it
      combines length modification with a reorientation of the distal ulna, to restore
      congruency of the distal radioulnar joint. When shortening a long ulna, this may
      help to regain a normal range of pronation and supination. When used to lengthen
      a short ulna, it stabilizes the distal ulna stump, which may be a cause of pain
      if unstable and can impinge on the radius. This lengthening is combined with soft
      tissue procedures to further stabilize the distal stump.Our experience in using
      it for shortening was mainly in Madelung deformity and, for lengthening, the
      sequelae of too large a distal ulna resection.

PMID- 16628121
TI  - Percutaneous release of A1 pulley.
AB  - We performed 100 percutaneous releases of the trigger digits in a cadaveric model
      using an 18-gauge needle. Successful percutaneous release was achieved for only
      59 digits (59%). No neurovascular injury occurred. We found that a percutaneous
      trigger digit release resulted in high percentage of incomplete releases of A1
      pulley, especially in the thumb, index, and little fingers.

PMID- 16628122
TI  - Using a fine forceps for rasping small bones.

PMID- 16628123
TI  - Therapeutic drug monitoring of mycophenolate mofetil in transplantation.
AB  - A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to
      guide immunosuppression with mycophenolate mofetil was held in New York in
      December 2004. Existing recommendations for the initial months after
      transplantation were updated. After ensuring adequate levels of mycophenolic acid
      (MPA, the active metabolite of mycophenolate mofetil) immediately after
      transplantation, optimal efficacy may require only a few dose adjustments,
      because intrapatient variability in exposure seems low. Recommendations based on
      current knowledge were made for posttransplantation sampling time points and for
      target MPA concentrations. Algorithms for estimating MPA exposure using limited
      sampling strategies were presented, and a new assay for MPA discussed. It was
      agreed that because of interpatient variability and the influence of concomitant
      immunosuppressants, TDM might help optimize outcomes, especially in patients at
      higher risk of rejection. The value of TDM in the general transplant population
      will be assessed from large, ongoing, randomized studies.

PMID- 16628124
TI  - Review of biologic matrices (urine, blood, hair) as indicators of recent or
      ongoing cannabis use.
AB  - Especially for cannabinoids, analytical procedures for the verification of recent
      use and generally for the assessment of the extent of drug abuse are of interest
      in clinical and forensic toxicology. For confirmation of abstinence, urine
      analysis seems to be a useful tool. Serial monitoring of THC-COOH to creatinine
      ratios can differentiate between recent drug use and residual THC-COOH excretion
      (THC-COOH/creatinine ratio > or = 0.5 compared with previous specimen ratio). For
      an assessment of the extent of cannabis use, the determination of free and bound
      THC-COOH and especially of THC and 11-OH-THC glucuronides are suggested as useful
      but need further confirmation. Blood analysis is preferred for the interpretation
      of acute effects after cannabis abuse. The cannabis influence factor (CIF) was
      demonstrated as a better tool to interpret the concentrations of THC and its
      metabolites in blood in forensic cases and therefore it was proposed to assume
      absolute driving inability because of cannabis intoxication from a CIF > or = 10.
      Additionally, a higher CIF is indicative of a recent cannabis abuse. Also
      discrimination between occasional use of cannabis and regular drug consumption is
      possible by analysis of THC-COOH in blood samples because of the long plasma half
      life of THC-COOH and its accumulation in the blood of frequent cannabis
      consumers. In routine tests, blood samples have to be taken within a prescribed 8
      day-period, and a THC-COOH concentration >75 ng/mL is assumed to be associated
      with regular consumption of cannabis products, whereas plasma THC-COOH
      concentrations <5 ng/mL are associated with occasional consumption. In contrast
      to other illicit drugs, hair analysis lacks the sensitivity to act as a detector
      for cannabinoids. THC and especially the main metabolite THC-COOH have a very low
      incorporation rate into hair and THC is not highly bound to melanin, resulting in
      much lower concentrations in hair compared with other drugs. Additionally, THC is
      present in cannabis smoke and also can be incorporated into the hair only by
      contamination. For the determination of the main metabolite THC-COOH in the
      picogram or femtogram per milligram range, which indicates an active consumption,
      special analytical procedures, such as GC/MS/MS techniques, are required.

PMID- 16628125
TI  - Comparison of the reintroduced MEIA assay with HPLC-MS/MS for the determination
      of whole-blood sirolimus from transplant recipients.
AB  - Therapeutic monitoring with dosage individualization of sirolimus drug therapy is
      standard clinical practice for organ transplant recipients. For several years
      sirolimus monitoring has been restricted as a result of lack of an immunoassay.
      The recent reintroduction of the microparticle enzyme immunoassay (MEIA) for
      sirolimus on the IMx analyser has the potential to address this situation. This
      study, using patient samples, has compared the MEIA sirolimus method with an
      established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established
      HPLC-UV assay was used for independent cross-validation. For quality control
      materials (5, 11, 22 microg/L), the MEIA showed acceptable validation criteria
      based on intra- and inter-run precision (CV) and accuracy (bias) of <8% and <13%,
      respectively. The lower limit of quantitation was found to be approximately 3
      microg/L. The performance of the immunoassay was compared with HPLC-MS/MS using
      EDTA whole-blood samples obtained from various types of organ transplant
      recipients (n = 116). The resultant Deming regression line was: MEIA =1.3 x HPLC
      MS/MS + 1.3 (r = 0.967, S(y/x) = 1) with a mean bias of 49.2% +/- 23.1% (range, 
      2.4% to 128%; P<0.001). The reason for the large and variable bias was not
      explored in this study, but the sirolimus-metabolite cross-reactivity with the
      MEIA antibody could be a substantive contributing factor. Whereas the MEIA
      sirolimus method may be an adjunct to sirolimus dosage individualization in
      transplant recipients, users must consider the implications of the substantial
      and variable bias when interpreting results. In selected patients where difficult
      clinical issues arise, reference to a specific chromatographic method may be
      required.

PMID- 16628126
TI  - An enzyme-linked immunosorbent assay for therapeutic drug monitoring of
      infliximab.
AB  - An enzyme-linked immunosorbent assay (ELISA) measuring serum infliximab
      concentrations in treated patients was developed. Microtiter plates were
      sensitized with tumor necrosis factor alpha (TNF-alpha) and saturated with
      phosphate-buffered saline (PBS) containing 1% bovine serum albumin (BSA). Samples
      diluted 1:100 in PBS-1% BSA were added and bound infliximab was detected using
      peroxidase-conjugated goat anti-human immunoglobulin G specific for Fc fragment
      (HRP-anti hIgG). Reading was performed using an ELISA plate reader. The limit of
      detection, calculated by assaying 10 replicates of a drug-free serum sample or
      blank sample and defined as the lowest concentration distinguishable from zero at
      2 standard deviations, was 0.014 microg/mL. Each quality control sample was
      tested on 7 occasions on 1 day and on 5 separate days. The intraday precision
      indices of the method were (percent coefficients of variation, CV%) 11.7%, 6.2%,
      and 6.9% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The
      corresponding bias measures (percent deviation) were -5.5%, -1.9%, and -7.9%,
      respectively. The between-days precision was 9.8%, 5.3%, and 5.3% for 0.04
      microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias
      were +0.3%, -0.3%, and -7.8%, respectively. Lower limit of quantitation and upper
      limit of quantitation were 0.04 microg/mL and 4.5 microg/mL, respectively. Trough
      serum concentrations of infliximab were measured in 6 adult patients with various
      diseases and in 5 pediatric patients with Crohn's disease. For the latter group,
      samples drawn 1 hour after the end of the infusion and repeated measurements also
      were available. Data were described using a 1-compartment population
      pharmacokinetic model. Terminal elimination half-life was 10.9 days. This method
      is rapid, accurate, and reproducible, and may be useful in therapeutic drug
      monitoring of infliximab.

PMID- 16628127
TI  - Limited penetration of lopinavir and ritonavir in the genital tract of men
      infected with HIV-1 in Brazil.
AB  - The concentrations of lopinavir and ritonavir in seminal and blood plasma and the
      seminal human immunodeficiency virus (HIV) viral load were quantified by HPLC and
      the Nuclisens assay, respectively, in a cross-sectional study of 16 HIV-1
      infected Brazilian men under stable treatment with a lopinavir/ritonavir
      containing antiretroviral regimen. Semen and blood samples were collected on 2
      occasions: at 6 to 60 minutes before ("trough"), and 5 to 6 hours after ("peak")
      ingestion of regular doses of lopinavir/ritonavir. Median seminal lopinavir
      levels were 120.6 ng/mL (range, <20-1481.8 ng/mL) and 233.1 ng/mL (range, 48.4
      1133.4 ng/mL) at trough and peak points, respectively. The corresponding values
      for ritonavir were 9.2 ng/mL (range, <5-47 ng/mL) and 17.1 ng/mL (range, 6.6-66.7
      ng/mL). The median concentrations of lopinavir and ritonavir in semen were,
      respectively, 1.9% to 3% and 3.7% to 4.4% of those measured in blood plasma
      samples collected within 30 minutes. HIV-1 viral load was detectable in the semen
      of 2 and in the blood of 6 of 16 patients. These results may have implications
      for drug-resistant HIV-1 evolution and transmission.

PMID- 16628128
TI  - Determination of paroxetine in human plasma by high-performance liquid
      chromatography using 7,7,8,8-tetracyanoquinodimethane as the derivatization
      reagent.
AB  - A selective and sensitive reversed-phase HPLC method was developed for the
      determination of the antidepressant paroxetine in plasma. The method is based on
      the purple chromogen formed by a displacement reaction of paroxetine with 7,7,8,8
      tetracyanoquinodimethane (TCNQ) in acetonitrile at 80 degrees C for 20 minutes.
      For the assay, the drug was extracted from 1 mL of plasma with chloroform and,
      after sample alkalinization, derivatized with TCNQ; then the reaction mixture was
      directly injected into a C18 column. Desipramine was used as internal standard.
      The mobile phase was acetonitrile-water (70:30) at a flow-rate of 1.0 mL/min, and
      the derivatives were eluted at 13.1 and 15.5 minutes for paroxetine and
      desipramine, respectively, and detected at 567 nm. Calibration curve was found
      linear over the range of 20-400 ng/mL, and the detection limit was 2 ng/mL at a
      signal-to-noise ratio of 3/1. Recoveries determined for 3 concentrations range
      between 81.3% and 88.1%. Intraday and interday relative standard deviation values
      were found to be within 3.8%-13.5% and 8.2%-14.6%, respectively. With this
      developed method, a pharmacokinetic study was performed for paroxetine.

PMID- 16628129
TI  - Quetiapine in overdosage: a clinical and pharmacokinetic analysis of 14 cases.
AB  - Data on quetiapine overdosage are only sparsely available in the literature. This
      study provides additional data on the pharmacokinetics and clinical effects of
      intoxication with this atypical antipsychotic drug. The authors performed a
      retrospective analysis of all quetiapine intoxications reported to and screened
      by the toxicological laboratory of the Central Hospital Pharmacy The Hague
      between January 1999 and December 2003. Cases with known suggested amount of
      intake and medical outcome were included. From the patient's medical record and
      from the toxicological laboratory findings, patient demographic characteristics
      (gender, age), details of quetiapine intoxication (estimated time of ingestion,
      estimated amount of ingestion, and coingested drugs) and clinical parameters were
      obtained. Severity of intoxication was graded by the Poisoning Severity Score
      (PSS). Individual pharmacokinetic parameter values were calculated using a one
      compartment open model and a Bayesian fitting procedure. Out of a total of 21
      intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested
      dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to
      8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood
      sampling at the emergency ward. The most frequent findings were somnolence and
      tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%),
      and severe in 3 patients (21%). Severity of intoxication was not associated with
      a higher amount of quetiapine intake. The authors found no correlation between
      the serum concentration of quetiapine and the amount ingested. Elimination t(1/2)
      was not prolonged. It can be concluded that quetiapine intoxications appear to
      proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our
      case series. No fatalities occurred. The severity of clinical symptoms was not
      associated with either a high serum concentration or the suggested amount
      ingested of quetiapine.

PMID- 16628130
TI  - Acute antidepressant response and plasma levels of bupropion and metabolites in a
      pediatric-aged sample: an exploratory study.
AB  - Studies examining associations between antidepressant response and plasma levels
      of bupropion and its metabolites have yielded contradictory findings. There have
      been no such studies in youth. This study explored such associations in 8 boys
      and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (SR)
      for major depression (n = 6) or depressive disorder not otherwise specified (n =
      10) as part of a pharmacokinetic (PK) study. All were started on morning doses of
      bupropion SR of 100 mg/day, and most eventually had doses increased to 200 mg/day
      because of inadequate clinical response. After taking prescribed dose of
      bupropion SR at least 14 days (median = 21 days), subjects had steady-state
      serial plasma levels of bupropion and its metabolites measured during a 24-hour
      period after morning doses. A total of 9 subjects underwent these PK assessments
      on doses of 100 mg/day, and 6 underwent these on doses of 200 mg/day, with 4
      studied on both doses. In this 24-hour assessment, the treating psychiatrist
      rated subjects' antidepressant response using the Clinical Global Impression's
      Improvement scale (CGI-I), blind to plasma levels, but informed by child and
      parent rating scales of depressive symptoms and clinical interviews. Relative to
      7 nonresponders, 9 responders (CGI-I < or = 2) had significantly higher mean
      areas under concentration curves for bupropion (P = 0.03), threohydrobupropion (P
      = 0.02), and erythrohydrobupropion (P = 0.02), and especially hyroxybupropion (P
      = 0.006). Plasma levels 7.5 hours after morning doses reaching the following cut
      points discriminated responders from nonresponders: bupropion > or = 37 ng/mL (P
      = 0.001), hydroxybupropion > or = 575 ng/mL (P = 0.003), threohydrobupropion > or
      = 240 ng/mL (P = 0.009), or erythrohydrobupropion > or = 45 ng/mL (P = 0.009).
      These preliminary findings suggest that plasma levels of bupropion and
      metabolites, particularly hydroxybupropion, may predict acute antidepressant
      response in depressed youths taking bupropion SR.

PMID- 16628131
TI  - Determination of docetaxel and Paclitaxel in human plasma by high-performance
      liquid chromatography: validation and application to clinical pharmacokinetic
      studies.
AB  - Taxanes, docetaxel and paclitaxel, represent important antineoplastic agents with
      broad spectra of antitumor activity. The authors developed and validated a high
      performance liquid chromatography method with ultraviolet detection for
      quantifying both taxanes in human plasma. The assay uses liquid-liquid extraction
      as sample treatment and an isocratic mobile phase and reversed-phase
      chromatography to determine docetaxel with paclitaxel as internal standard and
      vice versa. The lower limit of quantification was 0.015 mg/L. The assay had good
      recovery (87.96+/-14.05 and 90.57+/-9.63 for docetaxel and paclitaxel
      respectively) and precision: the within-day and between-days relative standard
      deviation of the mean for docetaxel (0.015-3 mg/L) and paclitaxel was always
      <10%. The method presented has been fully validated following the U.S. Food and
      Drug Administration requirements and has been successfully applied for the
      pharmacokinetic investigation of docetaxel or paclitaxel.

PMID- 16628132
TI  - Population pharmacokinetics of oxaliplatin (85 mg/m2) in combination with 5
      fluorouracil in patients with advanced colorectal cancer.
AB  - Pharmacokinetic (PK) studies of oxaliplatin, using a dose regimen of 85 mg/m, are
      lacking. A PK model may be used in future studies to investigate the relationship
      between pharmacokinetics and dose limiting toxicity. The purpose of this study
      was to construct a population PK model to describe platinum (Pt) concentrations
      in plasma in 33 patients with colorectal cancer. The secondary objective was to
      determine the relationship between the amount of Pt in 24-hour urine and the
      amount of Pt in fractionated urine collection periods. Plasma and urine samples
      were collected from patients during their first oxaliplatin treatment course.
      Population PK analysis was performed with WinNonMix. The model that best
      described the Pt concentrations in plasma was a two-compartment PK model. The
      elimination clearance (CL) and the elimination clearance of the peripheral
      compartment (CL2) (median +/- SE) were 25.2 +/- 6.3 L/hr and 68 +/- 24.8 L/hr,
      respectively. The median volume of distribution (V1) was determined to be 41.6 +/
      9.4 L and the median volume of distribution of the peripheral compartment (V2)
      was 452.5 +/- 96.4 L. The relationship between the cumulative amount of Pt in
      urine in the first 12 hours compared with the amount of Pt in 24 hours urine was
      reflected by a correlation coefficient (r2) of 0.95. The cumulative Pt
      concentration in urine in the first 10 hours and the first 8 hours compared with
      24 hours was reflected by correlation coefficients r2 = 0.93 and r2 = 0.897,
      respectively. This PK model could be useful in identifying predictors for PK and
      pharmacodynamic variability to individualize dosing. The results of this study
      suggest that fractionated urine samples can replace 24-hour urine collection.

PMID- 16628133
TI  - Dose individualization of carboplatin after a 120-hour infusion schedule: higher
      dose intensity but fewer toxicities.
AB  - Carboplatin (CBDCA) is a widely used anticancer agent for which dose-effect and
      dose-toxicity relationships have been demonstrated, thus stressing the need for a
      controlled exposure to this drug. So far, carboplatin administration could only
      be individualized a priori following 2 classic methods, which are based on the
      evaluation of renal clearance: Calvert's and Chatelut's formulas. This study was
      designed to develop and evaluate the performance of an alternative CBDCA 120-hour
      schedule coupled to a Bayesian adaptive dosing with feedback strategy. Precision
      of the dosing method was assessed in 84 patients (256 courses performed during a
      10-year period), by comparing CBDCA plasma concentrations observed at the end of
      the infusion with initial target values. A comprehensive monitoring of treatment
      related toxicities also was performed. Finally, the authors compared doses
      actually delivered following the dose-tailoring method with the theoretical,
      standard, ones calculated retrospectively with Calvert's and Chatelut's formulas.
      No significant differences were found between experimental and theoretical
      concentrations. According to the target exposure chosen (3 levels), the mean
      doses administered to our patients were 517, 719, and 902 mg of CBDCA compared
      with 550, 509, and 538 or 657, 604, and 644 mg, which would have been given
      following Calvert or Chatelut formulas, respectively. These results showed that
      our Bayesian method led to the administration of up to 60% higher doses of
      carboplatin compared with those based only on the evaluation of renal clearance.
      Despite the markedly higher doses administered, no severe toxicities were
      reported in the patients treated following this new schedule. It is noteworthy
      that neither hematologic growth factors nor stem cells, usually associated with
      high-dose regimen, were used as support in this study. These data strongly
      suggest that it is possible to deliver higher dose- intensities of carboplatin,
      even in elderly, unselected patients, without increasing toxicities and with no
      growth factor support, provided that a therapeutic drug monitoring strategy with
      real-time tailored dosing is performed.

PMID- 16628134
TI  - Pharmacokinetics of azithromycin in plasma, blood, polymorphonuclear neutrophils
      and sputum during long-term therapy in patients with cystic fibrosis.
AB  - Chronic therapy with the macrolide antibiotic azithromycin (AZM) is widely
      practiced in the treatment of patients with cystic fibrosis (CF) and chronic lung
      infection with Pseudomonas aeruginosa. Azithromycin dosage is variable, based on
      published studies, and not supported by pharmacokinetic data. This study
      describes the pharmacokinetics of the long-term administration of AZM (500 mg per
      day) in CF patients. AZM concentrations were quantified in the plasma, blood,
      isolated polymorphonuclear neutrophils (PMNNs), and sputum of 8 adult CF
      patients. The AZM distribution t1/2 was 0.1 hours in plasma. The (mean +/-
      standard deviation) elimination t(1/2) was 102 +/- 20 hours in plasma, 180 +/- 68
      hours in blood, and 289 +/- 166 hours in PMNNs. The C(max) of AZM was 0.67 +/-
      0.31 mg/L in plasma and 2.01 +/- 0.74 mg/L in blood, of which 1.44 +/- 0.69 mg/L
      was found in PMNNs. In sputum the concentration of AZM ranged from 12 to 53 mg/L
      and was still detectable at concentrations in the range 4 to 27 mg/L 10 days
      after the last dose. On average, the concentration in PMNNs was 2100 times the
      C(plasma) 24 hours after dosing AZM. These results confirm the accumulation of
      AZM in PMNNs. The authors conclude that sputum levels are elevated far above
      plasma and blood concentrations. The long t(1/2) in blood and PMNNs and the slow
      decrease in sputum levels indicate a less frequent dosing schedule (for instance
      once weekly) should be studied in future clinical trials of AZM in patients with
      cystic fibrosis.

PMID- 16628135
TI  - Population pharmacokinetics and dosing of amoxicillin in (pre)term neonates.
AB  - Amoxicillin plasma concentrations, pharmacokinetic parameters, and the influence
      of demographic, anthropometric, and clinical covariates were investigated in 150
      neonates. Gestational age (GA) ranged from 25 to 42 weeks and mean postnatal age
      (PNA) was 0.8 days. Amoxicillin concentrations were measured with reversed-phase
      HPLC in surplus plasma from routine assays of coadministered gentamicin. Mean
      total body clearance corrected for body weight (CL/W) was 0.096 +/- 0.036 L/kg(
      1)h(-1), mean elimination half-life (t(1/2)) was 5.2 +/- 1.9 hours, and mean
      volume of distribution corrected for body weight (V/W) was 0.65 +/- 0.13 L/kg.
      Multiple regression equations were calculated for the prediction of CL/W
      amoxicillin. CL/W gentamicin, V/W gentamicin, and GA were significant predictors
      of CL/W amoxicillin. Amoxicillin peak and trough concentrations after the second
      dose and the time the concentration exceeds the minimum inhibitory concentration
      (T>MIC), reached with the current dosage regimen, were evaluated. Toxic plasma
      concentrations were reached in several patients. Therefore, the authors have
      proposed a lower dosage regimen, based on GA, population pharmacokinetic
      parameters, bacterial susceptibility (T>MIC), and possible toxicity: 15 mg/kg per
      8 hours and 20 mg/kg per 8 hours for neonates with GA < or = 34 and GA>34 weeks,
      respectively. Simulation with this new dosage regimen indicated that satisfactory
      plasma concentrations were reached in all 150 neonates. Therefore, use of
      therapeutic drug monitoring and pharmacokinetic calculations for dosage
      adjustment is generally not necessary.

PMID- 16628136
TI  - Validation of a new high-performance liquid chromatography assay for nizatidine.
AB  - An expedient high-performance liquid chromatography (HPLC) assay for nizatidine
      measurement in human plasma was developed and validated. After deproteinization
      of 200 microL of plasma by filtration, nizatidine and 4-amino-antipyrine
      (internal standard) were separated (capacity ratio 3.0 and 6.63, respectively) on
      Nova-Pak C18 cartridge at room temperature (RT), and detected
      spectrophotometrically at 320 nm. The mobile phase, 0.02 mol/L disodium hydrogen
      phosphate, acetonitrile, methanol, and triethylamine (80:10:10:0.05 vol/vol), was
      delivered at 1.5 mL/min. Calibration curves were linear (r2 > or = 0.999) in the
      range 0.02 to 5 microg/mL, detection and quantification limits were 0.01 and 0.02
      microg/mL, respectively, intra-run and inter-run coefficients of variation were <
      or = 3.5% and < or = 4.2%, respectively, and recovery was >90%. Nizatidine was
      stable for at least 4 hours at RT, 12 weeks at -20 degrees C, and 3 freeze-thaw
      cycles in plasma; 16 hours at RT and 48 hours at -20 degrees C in deproteinized
      plasma; and 6 hours at RT and 3 weeks at -20 degrees C in water.

PMID- 16628137
TI  - A micromethod for the quantification of atenolol in plasma using high-performance
      liquid chromatography with fluorescence detection: therapeutic drug monitoring of
      two patients with severe coronary insufficiency before cardiac surgery.
AB  - A simple, rapid, selective, and sensitive analytical method was developed for the
      quantification of atenolol in small volumes of plasma, by high-performance liquid
      chromatography with fluorescence detection. Only 200 microL of plasma was used
      for chromatographic analysis. Separation was performed on a C18 reverse-phase
      column (4 microm) using a binary mobile phase consisting of 0.05 M of phosphate
      buffer, pH 5.5, and methanol (80:20, vol/vol) at a flow rate of 0.7 mL/minute.
      The retention times of atenolol and of the internal standard (sotalol) were 12.7
      and 10.4 minutes, respectively. Validation of this analytical method showed a
      good linear correlation (8-2000 ng/mL), high sensitivity (quantification limit: 8
      ng/ml and detection limit: 4 ng/mL), accuracy of 99.3%, and intraday and interday
      precision of 5.3% and 6.9%, respectively. Absolute recovery was 93.7%. The method
      was found to be robust, with acceptable stability. The analytical method was
      validated by the quantification of atenolol in plasma obtained from 2 patients
      with unstable angina, scheduled for myocardium revascularization surgery, who
      were chronically treated with 50 mg of atenolol administered per os once a day.
      The method developed was found to be adequate for use in pharmacokinetic studies
      and in adjusted dose pharmacotherapy.

PMID- 16628138
TI  - The in vivo glucuronidation of buprenorphine and norbuprenorphine determined by
      liquid chromatography-electrospray ionization-tandem mass spectrometry.
AB  - The opioid partial agonist medication, buprenorphine (BUP), and its primary
      metabolite, norbuprenorphine (NBUP), are extensively glucuronidated. Sensitive
      analytical methods that include determination of buprenorphine-3-glucuronide
      (BUPG) and norbuprenorphine-3-glucuronide (NBUPG) are needed to more fully
      understand the metabolism and pharmacokinetics of buprenorphine. A method has now
      been developed that uses solid-phase extraction followed by liquid chromatography
      electrospray ionization-tandem mass spectrometry. BUP-d4, NBUP-d3, and morphine-3
      glucuronide-d3 were used as internal standards. The lower limit of quantitation
      was 0.1 and 0.5 ng/mL for each of the analytes in 1-mL of human plasma and urine,
      respectively, except for NBUP in urine in which it was 2.5 ng/mL. The analytes
      were stable under the following conditions: plasma and urine at room temperature,
      up to 20 hours; plasma and urine at -20 degrees C for 119 and 85 days,
      respectively; plasma freeze-thaw, up to 3 cycles; processed sample, up to 96
      hours at -20 degrees C and up to 48 hours on the autosampler; stock solutions at
      room temperature and at -20 degrees C, up to 6 hours and 128 days, respectively.
      In plasma collected from 5 subjects on maintenance daily sublingual doses of 16
      mg BUP and 4 mg naloxone, respective 0- to 24-hour areas under the curve were 32,
      88, 26, and 316 ng/mL x h for BUP, NBUP, BUPG, and NBUPG. In urine samples
      respective percent of daily dose excreted in the 24-hour urine were 0.014%,
      1.89%, 1.01%, and 7.76%. This method allowed us to determine that NBUPG is a
      major metabolite present in plasma and urine of BUP. Because urinary elimination
      is limited ( approximately 11% of daily dose), the role of NBUPG in total
      clearance of buprenorphine is not yet known.

PMID- 16628139
TI  - Response of CEDIA amphetamines assay after a single dose of bitter orange.
AB  - Bitter orange has recently been substituted as an ingredient in many "ephedra
      free" dietary supplements used for weight loss. The primary active ingredient in
      bitter orange is synephrine. Previous reports have documented false-positive
      results from ephedrine with urine amphetamine assays. Because of the similarity
      in chemical structure of ephedrine and synephrine, it is hypothesized that
      ingestion of a bitter orange supplement may have the potential to cause false
      positive results with urine amphetamine assays. The purpose of this study was to
      determine the response of the CEDIA Amphetamines Assay after ingestion of bitter
      orange. Six healthy adult male volunteers were administered a single oral dose of
      Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to
      6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post
      administration. Additional urine specimens were collected from 1 subject at 9,
      12, and 15 hours after administration. All specimens were analyzed by the CEDIA
      Amphetamines Assay. Urine specific gravity and pH also were measured. All urine
      specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine
      specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus,
      reducing the possibility that the negative results were caused by diluted
      specimens or reduced excretion of synephrine into alkaline urine. This
      information will be of value when health care providers or those who interpret
      drug screens are asked to provide consultation regarding the interference of
      bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of
      Nature's Way Bitter Orange was not found to cause a false-positive response to
      the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

PMID- 16628140
TI  - Ketoconazole renders poor CYP3A phenotype status with midazolam as probe drug.
AB  - Drugs metabolized by cytochrome CYP3A isoenzymes have wide interindividual
      variability and normally distributed plasma clearance distributions. This makes
      precise dosing difficult to achieve clinically, which may compromise safe
      therapy. We hypothesized that with potent inhibition of CYP3A, we could
      clinically render patients "poor metabolizer" phenotype status, and thus reduce
      interindividual pharmacokinetic variability of midazolam, a well-known CYP3A
      substrate. Intravenous bolus midazolam at doses of 2.5 mg and 1 mg were
      administered to 28 and 29 patients with cancer with and without co-administration
      of 200 mg of oral ketoconazole twice per day respectively for 3 days, starting 1
      day before midazolam. Pharmacokinetic analyses of midazolam on both groups were
      derived using noncompartmental methods and compared. The mean clearance (CL) of
      midazolam was reduced 6 times by ketoconazole. Midazolam CL were normally
      distributed in both groups, and ranged from 1.7 to 51.9 and 1.4 to 8.2 L/hour in
      the control and ketoconazole groups, respectively, corresponding to a 7-fold
      reduction in dispersion between the 2 groups. Area-under-the-curve variability
      was reduced by >100%. A limited sampling model consisting of time points at 15
      and 300 minutes was validated as a phenotype for CYP3A activity to facilitate the
      use of midazolam as a probe drug for CYP3A activity. Potent inhibition of CYP3A
      by ketoconazole reduced midazolam CL and area-under-the-curve variability,
      allowing for more precise achievement of therapeutic target drug exposure.
      Prospective evaluation of this approach, together with dose adjustment based on
      limited sampling, seems warranted.

PMID- 16628141
TI  - Optimizing lithium dosing in hemodialysis.
AB  - We studied a 62-year-old female hemodialysis patient during initiation and
      maintenance of lithium carbonate therapy. Three different methods were applied to
      estimate the regimen: a scenario based on volume of distribution (V(d)), a
      scenario based on glomerular filtration rate (GFR), and a scenario in which we
      developed an algorithm based on a 2-compartment distribution without elimination.
      The GFR estimate led to plasma concentrations 3-4 times lower than those
      anticipated. In contrast, the estimates based on V(d) and the algorithm derived
      from pharmacokinetic modeling led to comparable loading dose estimates.
      Furthermore, the maintenance dose estimated from the central compartment (V1) led
      to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2
      mmol lithium was given after each hemodialysis session resulted in stable between
      dialysis plasma lithium concentrations in this patient with no residual kidney
      function. We did not observe adverse effects related to this regimen, which was
      monitored from 18 days to 8 months of therapy, and the patient experienced relief
      from her severe depressive disorder. In conclusion, dialysis patients may be
      treated with lithium administrated immediately postdialysis. Further observations
      are necessary to obtain robust long-term safety data and to optimize the
      monitoring schedule.

PMID- 16628142
TI  - Acute oxcarbazepine, benazepril, and hydrochlorothiazide overdose with alcohol.
AB  - An epiletic patient, suffering from partial complex seizures and hypertension,
      ingested approximately 42 g of oxcarbazepine (OXC) and an undefined number of
      tablets containing an association of benazepril and hydrochlorothiazide along
      with some glasses of wine. Four hours later he was brought to the emergency room.
      He was stuporous and gradually became unconscious. Therefore he was intubated
      and, approximately 6 hours after the overdose, transferred to the intensive care
      unit, where he underwent a 4-hour hemodialysis. Even if this procedure did not
      accelerate the elimination of the prodrug nor its active metabolite
      (monohydrocarbazepine), 3 hours after the end of dialysis the patient was fully
      recovered.

PMID- 16628143
TI  - Clinical outcomes of renal transplantation using liquid chromatographic
      monitoring of tacrolimus.
AB  - It is suggested that specific methods of Tacrolimus monitoring rather than
      immunoassays which over-estimate Tacrolimus levels, should be used in transplant
      recipients. There is limited data, however, comparing clinical outcomes of renal
      transplantation using each of these techniques. In this study, 40 renal
      transplant recipients with Tacrolimus monitoring by Microparticle Enzyme
      Immunoassay (MEIA; target trough level 10-15 ng/ml) were compared with 40
      patients monitored by High Performance Liquid Chromatography with Tandem Mass
      Spectrometry (HPLC-MS; target trough level 8-13 ng/ml). All received anti CD25
      antibody induction and Mycophenolate Mofetil in a steroid sparing protocol. No
      demographic differences were seen between MEIA and HPLC-MS groups. All patients
      were followed for 6 months. Patient survival was 100% in both groups; graft
      survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups
      did not differ in the number of dose changes required in the first 6 months or in
      the number of patients displaying Tacrolimus levels within target range at three
      and six months. Delayed graft function occurred in 14 patients in the MEIA group
      and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection
      occurred in 4 patients in the MEIA group and 1 patient in the HPLC-MS group (P =
      0.17). Biopsy proven acute Tacrolimus nephrotoxicity occurred in 6 patients in
      the MEIA group, and 7 in the HPLC-MS group (P = NS). No difference was seen in
      serum creatinine or estimated creatinine clearance at 3 or 6 months. No
      difference between groups was seen in systolic or diastolic blood pressure, or
      total cholesterol at 3 or 6 months. 2 patients in the MEIA group developed CMV
      disease and 1 developed posttransplantation diabetes mellitus. CMV and
      posttransplantation diabetes were not seen in the HPLC-MS group. 2 patients in
      each group developed reversible tremor. This study suggests that renal
      transplantation with HPLC-MS monitoring of Tacrolimus is safe and effective.

PMID- 16628144
TI  - Determination of mycophenolic acid plasma levels in renal transplant recipients
      co-administered sirolimus: comparison of an enzyme multiplied immunoassay
      technique (EMIT) and liquid chromatography-tandem mass spectrometry.
AB  - This study was designed to compare the enzyme multiplied immunoassay technique
      (EMIT) and a specific ;liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the determination of mycophenolic acid (MPA) concentrations in plasma
      samples collected from renal transplant patients receiving mycophenolate mofetil
      in association with sirolimus and corticosteroids. Ten-point blood concentration
      time profiles, between pre-dose (C0) and 9-hour post-dose, were obtained on day
      7, day 14, months 1, 2, and 3 posttransplantation in 8 patients. MPA plasma
      concentrations were measured simultaneously with both EMIT and LC-MS/MS. Higher
      concentrations were obtained with EMIT. The mean (+/-SD) absolute difference was
      +0.84 +/- 1.93 mg/L, which corresponds to a significant overestimation of 18.7 +/
      2 6.8% with EMIT, with variations depending on the time elapsed since
      transplantation. An EMIT overestimation of 16.7 +/- 22.5% also was obtained for
      the MPA areas under the curve calculated using the trapezoidal rule.

PMID- 16628145
TI  - Reliable new high-performance liquid chromatographic method for the determination
      of ciprofloxacin in human serum.
AB  - Ciprofloxacin is a broad-spectrum antibacterial drug, being used in a wide range
      of infections. A method to quantify the total (unbound + protein-bound)
      ciprofloxacin concentrations in human serum is presented based on rapid liquid
      liquid extraction, followed by reversed-phase liquid chromatography and UV
      detection at 280 nm. The calibration range used was 2 to 10 mg/L. The mean
      accuracy and precision (CV%) were all within specifications: at 0.2 mg/L 81.2%
      (10.1%), assigned to be the lower limit of quantification (LLOQ), at 8 mg/L
      103.6% (4.48%), at 14 mg/L 103.1% (3.98%). Metabolites and frequently used
      comedications showed minimal interference. Sample storage conditions suitable for
      routine determination of serum ciprofloxacin concentrations for daily therapeutic
      drug monitoring (gel-collection tubes and PVC tubes at 4 degrees C) and for
      intermittent batch-wise analyses for research purposes (PVC tubes at -18 degrees
      C) showed acceptable sample stability after storage for 48 hours (4 degrees C)
      and 6 months (-18 degrees C).

PMID- 16628146
TI  - The new enzyme-linked immunosorbent digoxin assay on the ADVIA Integrated Modular
      System is virtually free from oleander interference.
AB  - Despite known toxicity of oleander, this product is used in herbal preparations.
      Oleander interferes with various digoxin immunoassays. It is possible that a
      person taking digoxin also may take oleander-containing herbal products, and
      digoxin immunoassays interfering with oleander cannot be used for therapeutic
      monitoring of digoxin. Recently, Bayer Diagnostics introduced a new enzyme-linked
      chemiluminescent immunosorbent digoxin assay for application on the ADVIA IMS
      System (ECLIA-digoxin). We studied potential interference of oleander with this
      new digoxin assay and found that this assay is virtually free from oleander
      interference. When aliquots of drug-free serum pools were supplemented with ethyl
      alcohol extract of oleander leaf or pure oleandrin standard, we observed
      significant apparent digoxin concentration when measured by the fluorescence
      polarization immunoassay (FPIA) but minimal digoxin-like immunoreactivity using
      the ECLIA digoxin assay. Because cross-reactivity should be studied in the
      presence of primary analyte, we prepared 2 serum pools using sera from patients
      receiving digoxin. Then aliquots of first digoxin pool were supplemented with
      oleandrin standard and aliquots of second digoxin pool with oleander extract. We
      observed significant increases in apparent digoxin concentration in the presence
      of both oleandrin and oleander extract using the FPIA. However, we observed no
      statistically significant change in digoxin concentration when ECLIA digoxin
      assay was used, indicating that this assay is virtually free from oleander
      interference.

PMID- 16628147
TI  - False-positive results in urine drug screening in healthy volunteers
      participating in phase 1 studies with efavirenz and rifampin.

PMID- 16628148
TI  - Racial/ethnic differences in FIM scores and length of stay for underinsured
      patients undergoing stroke inpatient rehabilitation.
AB  - OBJECTIVE: To explore racial/ethnic differences in FIM data from admission to
      discharge in underinsured patients undergoing inpatient stroke rehabilitation.
      DESIGN: This is a retrospective analysis of the Uniform Data System for Medical
      Rehabilitation (UDSMR) database of an inpatient rehabilitation unit of a county
      hospital in a large urban city. Data included 171 adult patients admitted to the
      stroke rehabilitation unit between January 2000 and October 2003. Main outcome
      measures included admission and discharge total FIM score, FIM gain, FIM
      efficiency, and length of stay (LOS). Data were analyzed using chi analyses, t
      tests, univariate analysis of variance, binary logistic regression, and
      hierarchical multiple regression. RESULTS: Data from 68 Hispanic, 83 black, and
      20 white patients were included in the study. Univariate tests revealed that
      race/ethnicity groups differed significantly on admission FIM score (F=5.38,
      P<0.005), FIM gain (F=4.35, P<0.014), and FIM efficiency (F=3.42, P<0.035). Post
      hoc pairwise comparisons revealed that Hispanics had lower admission FIM scores
      than blacks (58.9 vs. 68.9). However, Hispanics had higher FIM gain scores than
      blacks (26.8 vs. 21.5). Race/ethnicity was not significantly related to age,
      gender, side of stroke, type of stroke, time from onset of stroke to
      rehabilitation admission, discharge FIM score, or LOS. Multiple regression
      analyses revealed that after controlling for all other available factors,
      race/ethnicity accounted for a significant amount of additional variance in
      admission FIM score (5.8%) and FIM efficiency (4.6%), but not in discharge FIM
      score, FIM gain, or LOS. Race/ethnicity was not predictive of discharge
      disposition. CONCLUSIONS: Differences in functional independence at admission to
      poststroke rehabilitation and the average daily improvement in function are
      related, in part, to patients' race/ethnicity. Differences in change in
      functional independence from admission to discharge (FIM gain) are not related to
      race/ethnicity once other factors, particularly admission FIM score, are taken
      into account. Future studies should identify reasons why Hispanics have lower
      admission FIM scores because demographic and stroke-related variables were not
      related to ethnicity yet have outcomes similar to blacks and whites at discharge.

PMID- 16628149
TI  - Skin problems in an amputee clinic.
AB  - OBJECTIVE: To document the type and frequency of individual residual limb skin
      problems among patients using a lower extremity prosthesis, including the
      suggested etiology and management of each type of skin problem. DESIGN: This is a
      6-yr retrospective chart review of skin lesions diagnosed in patients examined in
      an outpatient amputee clinic at a regional, referral rehabilitation hospital in
      Ottawa, Canada. Skin lesions were included if they were on a lower extremity
      residual limb for a patient who functionally used a prosthesis. Descriptive
      statistics were used to analyze data. RESULTS: A total of 528 skin problems were
      documented in 337 lower extremity residual limbs. Ulcers, irritations, inclusion
      cysts, calluses, and verrucous hyperplasia were the five most common skin
      problems representing 79.5% of all documented skin disorders. CONCLUSIONS: This
      study demonstrated that a wide variety of dermatologic conditions occurred
      frequently in the lower extremity amputee who functionally used a prosthesis.
      Five types of skin problems accounted for nearly 80% of the skin lesions
      identified. Future studies are required to evaluate prevention and management of
      the most frequent skin problems.

PMID- 16628150
TI  - Sleep disturbance in patients with chronic low back pain.
AB  - OBJECTIVE: To document the relationship between sleep disturbance and chronic low
      back pain in patients referred to a physical medicine and rehabilitation clinic.
      DESIGN: This is a prospective cross-sectional survey of 268 patients 18 yrs or
      older being evaluated for low back pain of greater than 6 months at a tertiary
      medical center. The survey consisted of a 43-item composite form that contained
      the Short-Form McGill Pain Questionnaire (SF-MPQ); the Pittsburgh Sleep Quality
      Index (PSQI); a pain visual analog scale (VAS); and questions regarding bed type,
      sleep position, and patients' sleep description. RESULTS: There was a significant
      relationship between pain and sleep (P<0.0005) with a 55% increase in the
      proportion of subjects reporting restless/light sleep after pain onset. There was
      no corresponding increase in sleep medication use. There was a significant direct
      correlation between SF-MPQ and PSQI (r=0.44, P<0.0005); between PSQI and VAS
      (r=0.41, P<0.0005); and between overall quality of sleep and VAS (r=0.31,
      P<0.0005). Finally, PSQI scores were the worst in subjects sleeping on an
      orthopedic mattress (P=0.001). CONCLUSIONS: Chronic low back pain significantly
      affects quality of sleep. Sleep problems should be addressed as an integral part
      of the pain management plan.

PMID- 16628151
TI  - Relationship between maximal exercise capacity and walking capacity in adult
      hemiplegic stroke patients.
AB  - OBJECTIVE: To evaluate the relationship between maximal exercise capacity and
      walking capacity in hemiplegic stroke patients. DESIGN: An uncontrolled
      observational study was conducted in the physical medicine and rehabilitation
      unit in an academic hospital. Participants were 21 hemiplegic stroke patients (18
      men, 3 women; age, 18-70 yrs) whose stroke occurred >3 mos before the study and
      who could walk independently with or without walking aids. Main outcome measures
      were peak oxygen uptake, workload, walking capacity, and motor impairment.
      RESULTS: There was a significant correlation between walking capacity (6-min-walk
      test) and both peak oxygen uptake (r=0.602, P=0.0032) and maximal power output
      (r=0.867, P<0.0001). CONCLUSIONS: Aerobic capacity and walking capacity are
      decreased in hemiplegic stroke patients and are correlated with each other. These
      results underscore the need for future studies, to confirm the role of fitness in
      relation to walking capacity, and to evaluate the benefit of integrating aerobic
      training into more traditional rehabilitation programs after stroke.

PMID- 16628152
TI  - Electrophysiological assessment of acupuncture points.
AB  - OBJECTIVE: This study was designed to assess the occurrence of end plate noise
      (EPN) in an acupuncture point (AcP). DESIGN: Ten male and 10 female normal
      volunteers were included in this study. For each subject, mapping of the
      distribution of EPN loci in an AcP region of Stomach-36 in one leg selected
      randomly, and also in a nearby non-AcP region in the other leg as a control, was
      performed with electromyographic recordings. RESULTS: There were significantly
      more EPN loci in the AcP region of Stomach-36 than in the non-AcP region near
      this AcP. Whenever the searching needle approached an EPN locus, the subjects
      always felt pain, soreness, or an unpleasant sensation. This feeling was rarely
      reported when no EPN was recorded from any site in either an AcP region or a non
      AcP region. After electromyographic study, every AcP was confirmed as a
      myofascial trigger point. CONCLUSIONS: Similar to the distribution of EPN loci in
      an MTrP region, significantly more EPN loci can be identified in an AcP region of
      Stomach-36 than in a nearby non-AcP site. This study provides additional support
      to the hypothesis that some AcPs are also myofascial trigger points.

PMID- 16628153
TI  - Role of blink reflex in diagnosis of subclinical cranial neuropathy in diabetic
      mellitus type II.
AB  - BACKGROUND AND OBJECTIVES: Peripheral neuropathy (PN) is one of the late
      complications of diabetes mellitus. Cranial nerves III, VII, and V are among the
      most commonly affected in diabetic patients. Traditional electrodiagnosis (Edx)
      studies are a useful method for diagnosis of PN and symptomatic cranial
      neuropathy, and may not be useful for detecting subclinical involvement of
      cranial nerves. The main objective of this study is to evaluate the role of blink
      reflex (BR) for early diagnosis of cranial neuropathy in diabetic patients with
      PN. DESIGN: A prospective study was performed on NIDDM patients with PN. One
      hundred eighty-eight subjects were included in our study in which 142 acted as
      healthy subjects and 46 as diabetic patients. Patients were excluded with prior
      history of cranial nerve lesions, stroke, or any other disease with
      polyneuropathy or drug-induced neuropathy. Routine nerve conduction studies were
      performed, and only patients with PN were included in this study. RESULTS:
      Abnormalities were found in 54.4% of patients. R1, IR2, and CR2 were prolonged
      relative to the healthy group. Statistically there was no significant difference
      in R/D ratio of patients (P=0.201). Also, there was a positive correlation
      between R1, IR2, and CR2 latencies with duration of diabetes and severity of
      polyneuropathy, but not for R/D. The greatest correlation was shown in R1 latency
      (69.9% abnormality). CONCLUSION: BR is a noninvasive and very useful method for
      the evaluation and diagnosis of subclinical cranial nerve involvement in diabetic
      patients.

PMID- 16628154
TI  - Early unplanned transfers from inpatient rehabilitation.
AB  - OBJECTIVE: To identify characteristics of patients who transfer off inpatient
      rehabilitation to a surgical or medical unit before completion of their
      rehabilitation program. DESIGN: A retrospective 9-yr chart review of patients
      transferred off the rehabilitation unit at a regional level 1 trauma center due
      to medical complications. RESULTS: Of 3072 patient admissions, 250 (8%) were
      transferred to an acute medical or surgical unit, and 55 (22%) of those transfers
      were within 3 days. Of the 250 patients, 33% had traumatic brain injury, 23% had
      spinal cord injury, 24% had stroke, 2% had amputations, 18% were in other
      diagnostic groups, and 23% were >64 yrs of age. When patients transferred early,
      only 47% were ultimately discharged to home, compared with approximately 72% of
      all discharges. The most common reasons for early transfer in these patients were
      infection (22%) and pulmonary complications (14%). Risk factors for early
      discharge included age of >64 yrs, spinal cord injury, or amputation. CONCLUSION:
      Patients admitted to the inpatient rehabilitation unit who have spinal cord
      injuries, amputations, or are >64 yrs old may have more medical/surgical
      complications. More detailed study of this patient population may help reduce the
      number of early transfers off the inpatient rehabilitation unit.

PMID- 16628156
TI  - Bone-density changes after stroke.
AB  - It has been many years since bone loss and fracture risk were first recognized as
      serious complications of stroke. Hip fracture is associated with a substantial
      increase in morbidity and mortality for stroke survivors, and therefore,
      assessing and maintaining skeletal health after stroke should be an important
      clinical goal. Recent long-term, prospective studies have illustrated a highly
      nonuniform pattern of bone changes after stroke. In general, there is significant
      bone loss on the paretic side, which is greatest in those patients with the most
      severe functional deficits. In some patients, bone loss in the paretic arm during
      the first year after stroke is the equivalent of >20 yrs of bone loss in healthy
      individuals of comparable age. Bone density in the nonparetic upper limb can
      actually increase after stroke, consistent with an increase in habitual use of
      the nonparetic hand. Bone density in the paretic lower limb can decrease by >10%
      in <1 yr, with smaller decreases being typical for the nonparetic lower limb.
      Despite the recent increase in the number of prospective, longitudinal studies,
      important questions about bone changes after stroke remain unanswered. Longer
      term studies quantifying bone loss for periods of >12 mos poststroke are needed
      to determine how long excess bone loss continues after stroke. Studies with more
      subjects and with more varied disability levels are needed to better understand
      the relationships between functional deficits and bone loss. New metrics are
      needed to quantify the intensity and duration of physical activity in the upper
      and lower limbs that are consistent with previous research on the role of
      mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health
      and the factors that affect bone quantity and quality should be a standard
      component in the clinical management of all survivors of stroke.

PMID- 16628157
TI  - Neurocognitive recovery from hypothyroid dementia after thyroid replacement
      therapy.

PMID- 16628158
TI  - Treating a pressure ulcer with bio-electric stimulation therapy.
AB  - Mr Jones lived independently until he developed necrotic pressure ulcers over his
      heels and could no longer mobilize to care for himself. He was transferred to a
      nursing home where he lived for 18 months and where the nurses could care for his
      wounds. The wound had been on his right heel without changing over the 18 months
      and, although attempts to hydrate the eschar had been somewhat successful, the
      necrotic tissue proved stubborn creating large quantity of fibrous slough. Mr
      Jones was initially assessed by the tissue viability consultant on 14 March 2005
      and agreed to the application of bio-electric stimulation therapy (POSiFEC). The
      wound change was immediate and was fully healed by 16 June 2005, 12 weeks after
      his initial assessment. This article outlines his care and the background to bio
      electrical stimulation in wounds.

PMID- 16628159
TI  - Perioperative analgesia: a factor in the development of heel pressure ulcers?
AB  - This article presents the incidence of heel pressure ulcers after an elective hip
      or a knee replacement. The majority of patients in the authors' institute receive
      either a neuraxial block (epidural and/or spinal) or peripheral nerve blocks
      (femoral and sciatic), depending on the anaesthetist's and surgeon's preference,
      and the patient's physical status. The past few years have seen increasing use of
      peripheral nerve blocks for knee replacement surgery. Patients with either the
      central or peripheral nerve blockade are at an increased risk of developing heel
      pressure ulcers. This article describes the experience at a tertiary referral
      centre and, in particular, highlights the risk of developing heel ulcers in
      patients receiving peripheral nerve blocks. Medical and nursing staff looking
      after these patients should be made aware of this complication and appropriate
      measures should be taken to prevent this avoidable complication.

PMID- 16628160
TI  - Complications of adapting pressure ulcer risk assessment scales.
AB  - This article challenges recommendations to adapt a pressure ulcer risk assessment
      scale (RAS) according to the clinical context. The transformation of the Cubbin
      and Jackson (1991) RAS is used to illustrate problems in scale development. When
      new factors are added to an existing scale, this can lead to unnecessary
      complexity. When words are changed by a person developing a scale this
      illustrates their differing beliefs and value judgements. Arbitrary scores for
      factors are misleading and in some cases mystifying, yet appear to be objective.
      This article suggests that the relationship between sub-scales and the whole
      scale have not been adequately accounted for -- they can't simply be added up
      arithmetically. The paradox of risk is debated, namely, that the more something
      is thought to be a risk, the less risky it becomes. RASs should be replaced by
      risk reduction scales linking a risk factor with its outcome following
      intervention.

PMID- 16628161
TI  - What price do we place on wound dressings?

PMID- 16628162
TI  - Anti-embolism stockings: are they used effectively and correctly?
AB  - Anti-embolism stockings are widely advocated in the prevention of deep vein
      thrombosis. But do they do more harm than good? This article explores the
      effectiveness of this intervention and the possible link with heel pressure
      ulceration, an increasing problem which costs the NHS millions of pounds and
      causes suffering to patients. With the aid of an audit tool the author assesses
      nursing knowledge and reveals that, although there is a high level of
      understanding regarding post-application care, the appropriate initiation of the
      intervention and subsequent documentation of this intervention are severely
      lacking, leaving the health profession wide open to litigation.

PMID- 16628164
TI  - The London Network for Nurses and Midwives.

PMID- 16628165
TI  - Nurse's poor moving and handling technique put patients at risk.

PMID- 16628166
TI  - Psychological impact of colostomy pouch change and disposal.
AB  - This article presents some of the findings from a multicentre cross-sectional
      correlational study to evaluate the relationship between colostomy pouch change
      and disposal practices and the patient's psychological wellbeing. Five
      questionnaires were used in a one-off interview with 86 patients. Patients were
      assessed at between one and four months postoperatively. Results from the Pouch
      Change and Disposal questionnaire showed that only 25% of patients found disposal
      of used appliances the most difficult part of their pouch change and disposal
      routine. Half felt that their body was out of their control and 33% reported
      avoiding social and leisure activities due to what was involved in their pouch
      change and disposal routine. Patients cited several factors, such as minimizing
      odour and having an appliance that could flush away, as factors which would help
      them to stop avoiding these activities. Stoma care nurses have a unique
      opportunity to improve the psychological wellbeing of their patients by
      considering the aspects of pouch change and disposal that pose the greatest
      challenge to individuals. Use of a modified version of the Pouch Change and
      Disposal questionnaire may be a useful tool in identifying those at risk of
      impaired quality of life.

PMID- 16628167
TI  - Parastomal hernia: an exploration of the risk factors and the implications.
AB  - Risk may be defined as 'the chance that something may happen to cause loss or an
      adverse effect' (Concise Oxford Medical Dictionary, 2003). Patients undergoing
      stoma formation are at risk of developing a wide range of complications following
      surgery. A parastomal hernia is an adverse effect that can contribute to
      postoperative morbidity. The risk of developing a parastomal hernia is dependent
      upon a number of variables, and stoma care nurses need to be aware of these to
      plan the appropriate care for patients undergoing stoma formation. This article
      discusses the issues surrounding the development of parastomal hernias and also
      looks at ways in which the risk factors associated with the development of a
      parastomal hernia may be minimized.

PMID- 16628168
TI  - Bed occupancy, turnover interval and MRSA rates in Northern Ireland.
AB  - The data describe bed turnover intervals (TI), bed percentage occupancy (PO) and
      methicillin-resistant Staphylococcus aureus (MRSA) rates per 1000 bed days of
      patient episodes. It was collected from annual hospital statistics in Northern
      Ireland (NI) and from the Communicable Diseases Surveillance Centre (CDSC) NI.
      The descriptive data show 6 of the general 11 surgical Trusts, out of a total of
      12 Trusts examined, had PO greater than 85%; and all 11 medical facilities in
      these Trusts had occupancy rates greater than 85%. A significant correlation was
      established between turnover interval and MRSA per 1000 bed days of patient
      episodes in acute services beds. The correlation of PO with MRSA rates was 0.49
      (ns). The conclusions drawn from the study are that in many Trusts the rates of
      bed occupancy for general surgery and general medicine is in excess of national
      guidelines and rapid turnover of patients is related to rates of MRSA infection.
      The implications for nurses and managers are discussed.

PMID- 16628169
TI  - Intravenous enzyme replacement therapy: better in home or hospital?
AB  - This article evaluates satisfaction with enzyme replacement therapy (ERT) at home
      and at hospital in adult patients with Fabry and Gaucher diseases. A
      questionnaire was developed and sent to 34 patients with Fabry disease who were
      receiving ERT with agalsidase alfa (Replagal) and to 49 patients with type I
      Gaucher disease who were receiving ERT with glucocerebrosidase (Cerezyme). Of the
      45 returned questionnaires, 20 were from patients with Fabry disease and 25 from
      patients with Gaucher disease. Hospital treatment visits were reported as
      stressful by 18 patients (40%), whereas only 4 (9%) patients reported that home
      therapy was stressful. Both groups of patients adjusted well to receiving home
      based therapy. Nearly all of the patients with Fabry disease (19 patients, 95%)
      and Gaucher disease (21 patients, 84%) preferred home-based therapy. Treatment in
      the home was reported as more comfortable, less stressful, more effective and had
      less impact on family life. Only 4 (9%) patients chose to continue receiving
      infusions in hospital. The majority of patients with Fabry disease and Gaucher
      disease found home-based therapy to be more convenient and less stressful than
      hospital-based therapy.

PMID- 16628170
TI  - Colostomy: getting patient consent to treatment for surgery.
AB  - This article explores the law relating to consent to treatment and the duty to
      inform a patient of the significant risks of serious harm which could arise from
      the treatment.

PMID- 16628171
TI  - The role of mentors in supporting pre-registration nursing students.
AB  - Students' practice experience is one of the most important aspects of their
      preparation for registration. There is currently considerable emphasis on
      improving this practice experience with adequate support and supervision. Mentors
      play a vital role in supporting, teaching and assessing students in practice.
      This article offers a literature-based discussion of the development and current
      practice of the mentor role in the support and assessment of students undertaking
      pre-registration programmes. The development of the mentor role is discussed.
      Issues relating to the role in nurse education today are addressed in relation to
      supporting, teaching and assessing students in practice and mentor
      accountability. This article discusses how Higher Education Institutions and
      universities and service managers might support mentors in their role. The
      implications for practice are outlined and include the NMC standards to support
      learning and assessment in practice due for publication in 2006.

PMID- 16628172
TI  - Generalist versus specialist nursing practice.

PMID- 16628173
TI  - Dying at home: a real patient choice?

PMID- 16628174
TI  - Exploring Aboriginal people's experience of relocation for treatment during end
      of-life care.
AB  - AIM: to explore indigenous peoples' experience of relocation for medical
      treatment during end-of-life care. METHODS: the data were collected from 72
      qualitative interviews conducted throughout the regional, rural and remote areas
      of the Northern Territory, Australia, with Aboriginal patients and carers and the
      health professionals who cared for them. RESULTS: relocation for indigenous
      peoples is a frightening experience. There are a myriad of fears including: the
      fear of leaving home, especially for people who had never been away from their
      home lands; the fear of dis-empowerment associated with leaving the support of
      family networks; fears about hospital environments and 'high-tech' treatments;
      fear of cultural alienation for familiar foods and ways of being; fear of travel;
      fear of loneliness; fear of language and communication barriers; financial fears;
      and fear of dying away from the homeland. CONCLUSION: the findings demonstrate
      the strong need for building-up local palliative care services and raise
      significant questions about the cultural appropriateness of the Western
      biomedical rationale for relocation during end-of-life care.

PMID- 16628175
TI  - Palliative care and pain control in Romania.

PMID- 16628176
TI  - Palliative care nurses' perceptions of the Edmonton Symptom Assessment Scale: a
      pilot survey.
AB  - AIM: to evaluate, at a pilot level, palliative care nurses' perceptions of the
      Edmonton Symptom Assessment Scale's (ESAS's) feasibility and usefulness. METHODS:
      all nurses working within the Edmonton Palliative Care Programme were provided
      with a one-page document containing five statements about the benefits and
      feasibility of the ESAS, and invited to rate each statement on a five-point
      Likert scale (1=strongly agree; 5=strongly disagree). RESULTS: of the 74 nursing
      staff employed in the programme, 48 (64.9%) chose to participate in this study.
      Perceptions of the ESAS were most favourable among the 22 registered nurses: 21
      (95.4%) believed the ESAS helped staff care for patients; and 17 (77.3%) believed
      patients benefited from implementation of the instrument. Most registered nurses
      found that the ESAS took little time and effort to complete. Licensed practical
      nurses and nursing attendants had a less favourable perception of the ESAS.
      CONCLUSION: the results of this pilot study demonstrate that palliative care
      nurses' perceptions of the ESAS are favourable generally, although they vary
      according to level of professional training. A full-scale study will be necessary
      to attain a more in-depth evaluation.

PMID- 16628177
TI  - Breaking bad news to parents: the children's nurse's role.
AB  - Breaking bad news is an extremely difficult and challenging process for the
      health care professional. The National Service Framework for Children in the UK
      highlights that the manner in which the health care professional delivers bad
      news impacts upon the way it is received, interpreted, understood and dealt with.
      The children's nurse, as an instrumental member of the multidisciplinary team
      caring for the child and family, is central to this complex communication
      process. This article examines the literature surrounding the breaking of bad
      news and introduces a new framework that outlines the multifaceted role of the
      children's nurse within this complex, challenging process.

PMID- 16628178
TI  - The impact of complementary therapy on mainstream practice.

PMID- 16628179
TI  - Evaluating an education programme in general palliative care for community
      nurses.
AB  - AIMS: To evaluate the effects of a palliative care education programme on the
      self-reported knowledge and confidence of 72 community nurses. DESIGN: a
      prospective longitudinal postal questionnaire survey was conducted. FINDINGS:
      seventy-one (99%) completed a pre-course questionnaire, 52 (72%) a questionnaire
      at completion of the course, and 37 (51%) a questionnaire one year later.
      Following the programme, more nurses felt that their professional needs were
      being met well or very well. Confidence in practice showed an increasing trend
      over time. Desire for education was lower on course completion than at its start.
      Palliative Care Nursing Quiz scores rose from a pre-course median of 12.5 to 15
      at course completion (P=0.001) which was maintained 1 year later. CONCLUSION: the
      education programme was successful in raising standards of knowledge,
      professional development and confidence. Improvement was maintained one year
      later.

PMID- 16628180
TI  - Interdisciplinary teams in palliative care: a critical reflection.
AB  - The notion of the interdisciplinary team as integral to the delivery of
      palliative care emerges clearly and consistently in palliative care philosophy
      and practice discourses. Many studies have found clear benefits of
      interdisciplinary palliative care teams. The empirical evidence supporting such
      teams, however, is not all positive. It is perhaps timely and appropriate to
      examine critically how palliative care interdisciplinary teams provide optimum
      support for patients and families. This article examines the notion that
      palliative care interdisciplinary teams are universally or inevitably effective
      and identifies potential barriers and constraints to effective teamwork. In
      particular, it is suggested that there is a need for careful examination of how
      teams function in the realm of 'psychosocial' care, and ways to look beyond
      rhetoric are articulated in order to facilitate teams to function more
      efficiently to provide optimum patient care.

PMID- 16628181
TI  - HIV transmission among male inmates in a state prison system--Georgia, 1992-2005.
AB  - The estimated prevalence of human immunodeficiency virus (HIV) infection is
      nearly five times higher for incarcerated populations (2.0%) than for the general
      U.S. population (0.43%). In 1988, the Georgia Department of Corrections (GDC)
      initiated mandatory HIV testing of inmates upon entry into prison and voluntary
      HIV testing of inmates on request or if clinically indicated. GDC offered
      voluntary HIV testing to inmates annually during July 2003-June 2005 and
      currently offers testing to inmates on request. During July 1988-February 2005, a
      total of 88 male inmates were known to have had both a negative HIV test result
      upon entry into prison and a subsequent confirmed positive HIV test result (i.e.,
      seroconversion) during incarceration. Of these 88 inmates, 37 (42%) had had more
      than one negative HIV test result before their HIV diagnosis. In October 2004,
      GDC and the Georgia Division of Public Health invited CDC to assist with an
      epidemiologic investigation of HIV risk behaviors and transmission patterns among
      male inmates within GDC facilities and to make HIV prevention recommendations for
      the prison population. This report describes the results of that investigation,
      which identified the following characteristics as associated with HIV
      seroconversion in prison: male-male sex in prison, tattooing in prison, older age
      (i.e., age of >26 years at date of interview), having served > or =5 years of the
      current sentence, black race, and having a body mass index (BMI) of < or =25.4
      kg/m2 on entry into prison. Findings from the investigation demonstrated that
      risk behaviors such as male-male sex and tattooing were associated with HIV
      transmission among inmates, highlighting the need for HIV prevention programs for
      this population.

PMID- 16628182
TI  - Monitoring poison control center data to detect health hazards during hurricane
      season--Florida, 2003-2005.
AB  - Eight hurricanes made landfall in Florida from August 13, 2004, through October
      24, 2005. Each hurricane caused flooding and widespread power outages. In the
      fall of 2004, the Florida Department of Health (FDOH) began retrospectively
      reviewing data collected by the Florida Poison Information Center Network (FPICN)
      during the 2004 hurricane season. During the 2005 hurricane season, FDOH, in
      consultation with FPICN, initiated daily monitoring of FPICN records of exposures
      that might reflect storm-related health hazards. Analysis of these data
      determined that 28 carbon monoxide (CO) exposures were reported to FPICN in the 2
      days after Hurricane Katrina made its August 25, 2005, landfall in Florida, en
      route to a second landfall on the Gulf Coast. Data on CO and other exposures were
      used to develop and distribute public health prevention messages to Florida
      communities affected by hurricanes.

PMID- 16628183
TI  - Rapid needs assessment of two rural communities after Hurricane Wilma--Hendry
      County, Florida, November 1-2, 2005.
AB  - On October 24, 2005, Hurricane Wilma, the most intense hurricane (882 mb) ever
      recorded in the Atlantic Basin, made landfall on the southern tip of Florida. By
      landfall, Wilma had been downgraded from a Category 5 (i.e., winds of > or =156
      mph) to a Category 3 hurricane but still contained winds of >110 mph. The storm
      moved slowly over the Florida Keys and south Florida, causing extensive wind and
      flood damage to homes and businesses. Approximately 3 million households were
      left without power, and thousands of residents were displaced to temporary
      shelters; 10 deaths were storm related. On October 27, the Florida Department of
      Health (FDOH) asked CDC and the North Carolina Division of Public Health (NCDPH)
      for assistance in performing a rapid needs assessment of communities most
      affected by the storm. On the basis of information from local public health
      officials, field assessment teams, and electric power companies, FDOH identified
      Hendry County, a rural county with a 2000 population of 36,210, as the most
      severely affected area. Two Hendry County communities, Montura Ranch Estates and
      Pioneer Plantation in the town of Clewiston (pop. 6,460), were of particular
      concern. According to the 2000 census, nearly 20% of Clewiston residents lived
      below the poverty level. The assessment determined that approximately one third
      of households also had been affected by at least one other hurricane that
      preceded Wilma during 2004 and 2005. More than half of the households surveyed
      lived in homes that were damaged but still habitable, and 10% of households in
      Montura Ranch Estates reported their homes as uninhabitable; approximately 73% of
      households had not received information about how to remain safe during clean-up
      activities. Results of the assessment were immediately provided to the Hendry
      County Emergency Operations Center, Hendry County Health Department, and FDOH for
      allocation of resources to help these communities recover from the hurricane.

PMID- 16628184
TI  - Update: influenza activity--United States, April 2-8, 2006.
AB  - During April 2-8, 2006, the number of states reporting widespread influenza
      activity decreased to 10. Ten states reported regional activity, 15 reported
      local activity, 14 reported sporadic activity, and one reported no activity. The
      percentage of specimens testing positive for influenza decreased in the United
      States. During the preceding 3 weeks (weeks 12-14), the percentage of specimens
      testing positive for influenza ranged from 26.4% in the South Atlantic region to
      12.5% in the Mid-Atlantic region. During this period, regions reporting the
      highest proportion of isolates as influenza B included the Pacific (62.5%),
      Mountain (61.8%), and West North Central (61.2%) regions. Other regions reporting
      more than 30.0% of recent isolates as influenza B include the East North Central,
      West South Central, and New England regions. The percentage of outpatient visits
      for influenza-like illness (ILI) during the week ending April 8 was below the
      national baseline. The percentage of deaths attributed to pneumonia and influenza
      (P&I) was below the epidemic threshold for the week ending April 8.

PMID- 16628185
TI  - Chromosomal aberrations in leukaemia cells may delete tumour target antigens of
      stem cell-based immunotherapy.

PMID- 16628186
TI  - A novel MHC-associated proteinase 3 peptide isolated from primary chronic myeloid
      leukaemia cells further supports the significance of this antigen for the
      immunotherapy of myeloid leukaemias.
AB  - Three of the most promising antigens for immunotherapy of chronic myelogenous
      leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the
      overexpressed proteins WT1 and Proteinase 3. The clinical significance of
      Proteinase 3 as a target in myelogenous leukaemias has been bolstered by
      detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this
      antigen in patients undergoing immune therapies. Our investigation aimed to
      directly identify MHC-ligands derived from these antigens and presented on CML
      blasts by means of affinity-purification and mass spectrometric peptide
      sequencing. Although no known or potential new epitopes were discovered for
      Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more
      abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic
      proteins overexpressed as a result of Bcr/Abl transformation were also
      identified. Our investigation is the second of only a small number of studies to
      identify a peptide from Proteinase 3 among the more abundant MHC-associated
      peptides and thus implies that peptides from this antigen are among the more
      abundantly presented of the known leukaemic antigens. Taken in conjunction with
      clinical observations of functional Proteinase 3 specific CTL in patients', these
      data further support the application of this antigen as an immunotherapeutical
      target for myelogenous leukaemias.

PMID- 16628187
TI  - A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need
      for a prospective, multicenter initiative for rare 'poor prognosis' myeloid
      malignancies.

PMID- 16628188
TI  - The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic
      lymphocytic leukemia cells in vitro.
AB  - We have studied the in vitro actions of the sesquiterpene lactone parthenolide
      (PTL) on cells isolated from patients with chronic lymphocytic leukemia (CLL).
      Dye reduction viability assays showed that the median LD(50) for PTL was 6.2 muM
      (n=78). Fifteen of these isolates were relatively resistant to the conventional
      agent chlorambucil but retained sensitivity to PTL. Brief exposures to PTL (1-3
      h) were sufficient to induce caspase activation and commitment to cell death.
      Chronic lymphocytic leukemia cells were more sensitive towards PTL than were
      normal T lymphocytes or CD34(+) haematopoietic progenitor cells. The mechanism of
      cell killing was via PTL-induced generation of reactive oxygen species, resulting
      in turn in a proapoptotic Bax conformational change, release of mitochondrial
      cytochrome c and caspase activation. Parthenolide also decreased nuclear levels
      of the antiapoptotic transcription factor nuclear factor-kappa B and diminished
      phosphorylation of its negative regulator IkappaB. Killing of CLL cells by PTL
      was apparently independent of p53 induction. This is the first report showing the
      relative selectivity of PTL towards CLL cells. The data here warrant further
      investigation of this class of natural product as potential therapeutic agents
      for CLL.

PMID- 16628189
TI  - Pathogen-associated molecular patterns are growth and survival factors for human
      myeloma cells through Toll-like receptors.
AB  - Multiple myeloma (MM) patients are strongly vulnerable to infections, which
      remain a major cause of death. During infection, human immune cells sense the
      presence of invading pathogens through the Toll-like receptor family (TLR), which
      recognizes pathogen-associated molecular patterns (PAMP). We hypothesized that MM
      cells also could sense the presence of microorganisms, thus promoting myeloma
      disease progression. Here, we report that human myeloma cell lines (HMCL) and
      primary myeloma cells express a broad range of TLR, and are sensitive to the
      corresponding PAMP. Toll-like receptor 1, 7 and 9 are most frequently expressed
      by HMCL. The expression pattern of TLR does not correlate with the one of B
      cells, as TLR2 and 10 are lost while TLR3, 4 and 8 are acquired by some HMCL.
      Culture with TLR7- and TLR9-ligands saves HMCL from serum-deprivation or
      dexamethasone-induced apoptosis. Similarly, both ligands increase myeloma cell
      growth. These effects are mediated by an autocrine secretion of interleukin-6 (IL
      6) since the neutralization of IL-6 blocks the growth and survival of HMCL. Thus,
      TLR expression and function are not restricted to the cells of the immune system
      and could be of advantage for cancer cells. In MM, recurrent infections could
      promote tumor growth and favor escape from standard therapies.

PMID- 16628190
TI  - Physical association of the patient-specific GATA1 mutants with RUNX1 in acute
      megakaryoblastic leukemia accompanying Down syndrome.
AB  - Mutations of the GATA1 gene on chromosome X have been found in almost all cases
      of transient myeloproliferative disorder and acute megakaryoblastic leukemia
      (AMKL) accompanying Down syndrome (DS). Although most GATA1 mutations lead to the
      expression of GATA1s lacking the N-terminal activation domain, we recently found
      two novel GATA1 proteins with defects in another N-terminal region. It has been
      suggested that loss of the N-terminal portion of GATA1 might interfere with
      physiological interactions with the critical megakaryocytic transcription factor
      RUNX1, and this would imply that GATA1s is not able to interact properly with
      RUNX1. However, the interaction domain of GATA1 remains controversial. In this
      study, we show that GATA1 binds to RUNX1 through its zinc-finger domains, and
      that the C-finger is indispensable for synergy with RUNX1. All of the patient
      specific GATA1 mutants interacted efficiently with RUNX1 and retained their
      ability to act synergistically with RUNX1 on the megakaryocytic GP1balpha
      promoter, whereas the levels of transcriptional activities were diverse among the
      mutants. Thus, our data indicate that physical interaction and synergy between
      GATA1 and RUNX1 are retained in DS-AMKL, although it is still possible that
      increased RUNX1 activity plays a role in the development of leukemia in DS.

PMID- 16628191
TI  - ArgBP2, encoding a negative regulator of ABL, is fused to MLL in a case of infant
      M5 acute myeloid leukemia involving 4q35 and 11q23.

PMID- 16628192
TI  - Identification and characterization of a novel zinc finger protein (HZF1) gene
      and its function in erythroid and megakaryocytic differentiation of K562 cells.
AB  - A novel zinc finger protein (HZF1) gene was identified and characterized by
      screening a human bone marrow cDNA library, using a new expression sequence tag
      probe that contains sequences encoding zinc finger motifs. There are at least
      three transcripts that may result from different splicing of the pre-mRNA, but
      the differences among them are only involved in 5' non-translation region of HZF1
      mRNA. HZF1 gene contains four exons and three introns. The putative protein
      consists of 670 amino-acid residues including 15 typical C2H2 and 2 C2RH zinc
      finger motifs. This structure characterization of HZF1 and the nuclear location
      of the protein suggest that HZF1 may function as a transcription factor. HZF1
      mRNA expression was detected in ubiquitous tissues and various hematopoietic cell
      lines. Increased HZF1 mRNA expression was observed following erythroid
      differentiation of K562 cells induced by hemin or megakaryocytic differentiation
      of K562 cells induced by phorbol myristate acetate (PMA). Both of the antisense
      method and RNA interference assay revealed that repression of the intrinsic
      expression of HZF1 blocked the hemin-induced erythroid differentiation and
      reduced the PMA-induced megakaryocytic differentiation of K562 cells, which
      suggested that HZF1 play important roles in erythroid and megakaryocytic
      differentiation.

PMID- 16628193
TI  - Reliability of quantitative chimerism results: assessment of sample performance
      using novel parameters.

PMID- 16628194
TI  - Blockade of experimental atopic dermatitis via topical NF-kappaB decoy
      oligonucleotide.
AB  - Atopic dermatitis (AD) is a common chronic skin inflammatory disease. Long-term
      use of topical corticosteroids in skin inflammation poses risks of systemic and
      local side effects. The NF-kappaB transcription factor family plays a central
      role in the progression and maintenance of AD. This study explores the
      possibility of using topical NF-kappaB Decoy as a novel therapeutic alternative
      for targeting Th1/Th2-driven skin inflammation in experimental AD. A high
      affinity, topical NF-kappaB Decoy developed for human efficacy demonstrates: (i)
      efficient NF-kappaB Decoy penetration in pig skin, (ii) NF-kappaB Decoy nuclear
      localization in keratinocytes and key immune cells, and (iii) potent "steroid
      like" efficacy in a chronic dust-mite antigen skin inflammation treatment model.
      NF-kappaB Decoy exerts its anti-inflammatory action through the effective
      inhibition of essential regulators of inflammation and by induction of apoptosis
      of key immune cells. Unlike betamethasone valerate (BMV), long-term NF-kappaB
      Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappaB Decoy,
      in contrast to BMV, restores compromised stratum corneum integrity and barrier
      function. Steroid withdrawal causes rapid rebound of inflammation, while the NF
      kappaB Decoy therapeutic benefit was maintained for weeks. Thus, topical NF
      kappaB Decoy provides a novel mechanism of reducing chronic skin inflammation
      with improved skin homeostasis and minimal side effects.

PMID- 16628195
TI  - New insights into ultrastructure, lipid composition and organization of vernix
      caseosa.
AB  - The upper layer of the epidermis, the stratum corneum (SC), is very important for
      skin barrier function. During the last trimester of gestation, the SC of the
      fetus is protected by a cheesy, white biofilm called vernix caseosa (VC). VC
      consists of water-containing corneocytes embedded in a lipid matrix and the basic
      structure shows certain similarities with the SC. This study aimed to
      characterize VC, with the main focus on an integral analysis of free and (to the
      corneocytes) bound lipids, on the lipid organization, and on ultrastructure. Free
      lipids of VC show a wide distribution in polarity; nonpolar lipids such as sterol
      esters and triglycerides predominate, having a chain length of up to 32 carbon
      atoms. The profile of fatty acids, omega-hydroxyacids and omega-hydroxyceramides 
      representing the bound lipids of VC - shows high similarity to that of SC.
      Morphological studies revealed the presence of highly hydrated corneocytes
      embedded in lipids, the latter being occasionally accumulated as lipid pools.
      Freeze fracture electron microscopy showed smooth surfaces of corneocytes and a
      heterogeneous appearance of intercellular lipids. The results suggest a lower
      degree of ordering of VC lipids as compared to the SC. A small-angle X-ray
      diffraction study showed similar results.

PMID- 16628196
TI  - SOCS1-negative feedback of STAT1 activation is a key pathway in the dsRNA-induced
      innate immune response of human keratinocytes.
AB  - Toll-like receptor (TLR)3 is a receptor for virus-associated double-stranded RNA,
      and triggers antiviral immune responses during viral infection. Epidermal
      keratinocytes express TLR3 and provide an innate immune defense against viral
      infection. Since the intracellular regulatory mechanism is unknown, we
      hypothesized that the signal transducers and activators of transcription (STAT)
      suppressors of cytokine signaling (SOCS) system regulates the innate immune
      response of keratinocytes. Treatment with polyinosinic-polycytidylic acid
      (poly(I:C)) resulted in the rapid translocation of IFN regulatory factor (IRF)-3
      into the nucleus, followed by phosphorylation of STAT1 and STAT3. The activation
      of STATs by poly(I:C) probably occurs in an indirect fashion, through poly(I:C)
      induced IFN. We infected cells with the dominant-negative forms of STAT1
      (STAT1F), STAT3 (STAT3F), and SOCS1 using adenovirus vectors. Infection with
      STAT1F suppressed the induction of macrophage inflammatory protein (MIP)-1alpha
      by poly(I:C), whereas STAT3F had a minimal effect, which indicates that STAT1
      mediates MIP-1alpha induction. SOCS1, which is a negative feedback regulator of
      STAT1 signaling, was induced by treatment with poly(I:C). SOCS1 infection
      inhibited the phosphorylation of STAT1 and significantly reduced poly(I:C)
      induced MIP-1alpha production. Furthermore, STAT1-SOCS1 regulated poly(I:C)
      induced TLR3 and IRF-7 expression. However, SOCS1 did not affect NF-kappaB
      signaling. Thus, the STAT1-SOCS1 pathway regulates the innate immune response via
      TLR3 signaling in epidermal keratinocytes.

PMID- 16628197
TI  - Early death from cardiomyopathy in a family with autosomal dominant striate
      palmoplantar keratoderma and woolly hair associated with a novel insertion
      mutation in desmoplakin.

PMID- 16628198
TI  - Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin-
      and chymotrypsin-like hyperactivity in Netherton syndrome.
AB  - SPINK5 (serine protease inhibitor Kazal-type 5), encoding the protease inhibitor
      LEKTI (lympho-epithelial Kazal-type related inhibitor), is the defective gene in
      Netherton syndrome (NS), a severe inherited keratinizing disorder. We have
      recently demonstrated epidermal protease hyperactivity in Spink5(-/-) mice
      resulting in desmosomal protein degradation. Herein, we investigated the
      molecular mechanism underlying the epidermal defect in 15 patients with NS. We
      demonstrated that, in a majority of patients, desmoglein 1 (Dsg1) and desmocollin
      1 (Dsc1) were dramatically reduced in the upper most living layers of the
      epidermis. These defects were associated with premature degradation of
      corneodesmosomes. Stratum corneum tryptic enzyme (SCTE)-like and stratum corneum
      chymotryptic enzyme (SCCE)-like activities were increased, suggesting that these
      proteases participate in the premature degradation of corneodesmosomal cadherins.
      SCTE and SCCE expression was extended to the cell layers where Dsg1 and Dsc1
      immunostaining was reduced. In contrast, a subset of six patients with normal
      epidermal protease activity or residual LEKTI expression displayed apparently
      normal cadherin expression and less severe disease manifestations. This suggests
      a degree of correlation between cadherin degradation and clinical severity. This
      work further supports the implication of premature corneodesmosomal cadherin
      degradation in the pathogenesis of NS and provides evidence for additional
      factors playing a role in disease expression.

PMID- 16628199
TI  - Integrative pharmacology and drug discovery--is the tide finally turning?
AB  - In vivo animal experiments are essential (and a regulatory requirement) to
      demonstrate the potential efficacy, safety and pharmacodynamic/pharmacokinetic
      profile of candidate drugs. However, the number of pharmacologists (and other
      bioscientists) with integrative (in vivo) pharmacology skills has been in decline
      for a number of years, as have the opportunities for students to learn such
      skills. This article reviews some recent initiatives that are underway to rebuild
      this essential skills base in the United Kingdom and the United States.
      Partnerships between industry and national funders of research and education have
      proved to be a particularly effective approach to support this strategically
      important area of biological science.

PMID- 16628200
TI  - MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis.
AB  - Macrophage migration inhibitory factor (MIF) is well established as a key
      cytokine in immuno-inflammatory diseases such as rheumatoid arthritis.
      Inflammation is now also recognized as having a crucial role in atherosclerosis,
      and recent evidence indicates that MIF could also be important in this disease.
      Here, we review the role of MIF in rheumatoid arthritis and atherosclerosis,
      discuss the ways in which MIF and its relationship with glucocorticoids could
      link these diseases, and consider the potential of MIF as a new therapeutic
      target for small-molecule and antibody-based anti-cytokine drugs.

PMID- 16628201
TI  - GFP expression in muscle cells impairs actin-myosin interactions: implications
      for cell therapy.

PMID- 16628202
TI  - Increasing the power of cytometry.

PMID- 16628203
TI  - Imaging activity in brain cells: deconvolution clears the haze.

PMID- 16628204
TI  - Detection and localization of single molecular recognition events using atomic
      force microscopy.
AB  - Because of its piconewton force sensitivity and nanometer positional accuracy,
      the atomic force microscope (AFM) has emerged as a powerful tool for exploring
      the forces and the dynamics of the interaction between individual ligands and
      receptors, either on isolated molecules or on cellular surfaces. These studies
      require attaching specific biomolecules or cells on AFM tips and on solid
      supports and measuring the unbinding forces between the modified surfaces using
      AFM force spectroscopy. In this review, we describe the current methodology for
      molecular recognition studies using the AFM, with an emphasis on strategies
      available for preparing AFM tips and samples, and on procedures for detecting and
      localizing single molecular recognition events.

PMID- 16628205
TI  - A highly flexible tRNA acylation method for non-natural polypeptide synthesis.
AB  - Here we describe a de novo tRNA acylation system, the flexizyme (Fx) system, for
      the preparation of acyl tRNAs with nearly unlimited selection of amino and
      hydroxy acids and tRNAs. The combination of the Fx system with an appropriate
      cell-free translation system allows us to readily perform mRNA-encoded synthesis
      of proteins and short polypeptides involving multiple non-natural amino acids.

PMID- 16628206
TI  - Fluorescent cell barcoding in flow cytometry allows high-throughput drug
      screening and signaling profiling.
AB  - Flow cytometry allows high-content, multiparameter analysis of single cells,
      making it a promising tool for drug discovery and profiling of intracellular
      signaling. To add high-throughput capacity to flow cytometry, we developed a cell
      based multiplexing technique called fluorescent cell barcoding (FCB). In FCB,
      each sample is labeled with a different signature, or barcode, of fluorescence
      intensity and emission wavelengths, and mixed with other samples before antibody
      staining and analysis by flow cytometry. Using three FCB fluorophores, we were
      able to barcode and combine entire 96-well plates, reducing antibody consumption
      100-fold and acquisition time to 5-15 min per plate. Using FCB and phospho
      specific flow cytometry, we screened a small-molecule library for inhibitors of T
      cell-receptor and cytokine signaling, simultaneously determining compound
      efficacy and selectivity. We also analyzed IFN-gamma signaling in multiple cell
      types from primary mouse splenocytes, revealing differences in sensitivity and
      kinetics between B cells, CD4+ and CD4- T cells and CD11b-hi cells.

PMID- 16628207
TI  - Probing the role of multicellular organization in three-dimensional
      microenvironments.
AB  - Successful application of living cells in regenerative medicine requires an
      understanding of how tissue structure relates to organ function. There is growing
      evidence that presentation of extracellular cues in a three-dimensional (3D)
      context can fundamentally alter cellular responses. Thus, microenvironment
      studies that previously were limited to adherent two-dimensional (2D) cultures
      may not be appropriate for many cell types. Here we present a method for the
      rapid formation of reproducible, high-resolution 3D cellular structures within a
      photopolymerizable hydrogel using dielectrophoretic forces. We demonstrate the
      parallel formation of >20,000 cell clusters of precise size and shape within a
      thin 2-cm(2) hydrogel and the maintenance of high cell viability and
      differentiated cell markers over 2 weeks. By modulating cell-cell interactions in
      3D clusters, we present the first evidence that microscale tissue organization
      regulates bovine articular chondrocyte biosynthesis. This platform permits
      investigation of tissue architecture in other multicellular processes, from
      embryogenesis to regeneration to tumorigenesis.

PMID- 16628208
TI  - Reconstruction of firing rate changes across neuronal populations by temporally
      deconvolved Ca2+ imaging.
AB  - Methods to record action potential (AP) firing in many individual neurons are
      essential to unravel the function of complex neuronal circuits in the brain. A
      promising approach is bolus loading of Ca(2+) indicators combined with
      multiphoton microscopy. Currently, however, this technique lacks cell-type
      specificity, has low temporal resolution and cannot resolve complex temporal
      firing patterns. Here we present simple solutions to these problems. We
      identified neuron types by colocalizing Ca(2+) signals of a red-fluorescing
      indicator with genetically encoded markers. We reconstructed firing rate changes
      from Ca(2+) signals by temporal deconvolution. This technique is efficient,
      dramatically enhances temporal resolution, facilitates data interpretation and
      permits analysis of odor-response patterns across thousands of neurons in the
      zebrafish olfactory bulb. Hence, temporally deconvolved Ca(2+) imaging (TDCa
      imaging) resolves limitations of current optical recording techniques and is
      likely to be widely applicable because of its simplicity, robustness and generic
      principle.

PMID- 16628209
TI  - High-throughput RNAi screening by time-lapse imaging of live human cells.
AB  - RNA interference (RNAi) is a powerful tool to study gene function in cultured
      cells. Transfected cell microarrays in principle allow high-throughput phenotypic
      analysis after gene knockdown by microscopy. But bottlenecks in imaging and data
      analysis have limited such high-content screens to endpoint assays in fixed cells
      and determination of global parameters such as viability. Here we have overcome
      these limitations and developed an automated platform for high-content RNAi
      screening by time-lapse fluorescence microscopy of live HeLa cells expressing
      histone-GFP to report on chromosome segregation and structure. We automated all
      steps, including printing transfection-ready small interfering RNA (siRNA)
      microarrays, fluorescence imaging and computational phenotyping of digital
      images, in a high-throughput workflow. We validated this method in a pilot screen
      assaying cell division and delivered a sensitive, time-resolved phenoprint for
      each of the 49 endogenous genes we suppressed. This modular platform is scalable
      and makes the power of time-lapse microscopy available for genome-wide RNAi
      screens.

PMID- 16628210
TI  - Metabolic biotinylation of cell surface receptors for in vivo imaging.
AB  - We have developed a versatile, potent technique for imaging cells in culture and
      in vivo by expressing a metabolically biotinylated cell-surface receptor and
      visualizing it with labeled streptavidin moieties. The recombinant reporter
      protein, which incorporates a biotin acceptor peptide (BAP) between an N-terminal
      signal sequence and a transmembrane domain, (BAP-TM) was efficiently biotinylated
      by endogenous biotin ligase in mammalian cells with the biotin displayed on the
      cell surface. Tumors expressing the BAP-TM have high sensitivity for magnetic
      resonance and fluorescence tomographic imaging in vivo after intravascular
      injection of streptavidin conjugated to magnetic nanoparticles or fluorochromes,
      respectively. Moreover, streptavidin-horseradish peroxidase conjugates in
      conjunction with a peroxidase-sensitive gadolinium agent further increased and
      prolonged the magnetic resonance signal. This BAP-TM allows noninvasive real-time
      imaging of any cell type transduced to express this reporter protein in culture
      or in vivo.

PMID- 16628211
TI  - Delivery of short hairpin RNAs--triggers of gene silencing--into mouse embryonic
      stem cells.

PMID- 16628213
TI  - Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila
      melanogaster.
AB  - Polycomb group (PcG) proteins maintain transcriptional repression of
      developmentally important genes and have been implicated in cell proliferation
      and stem cell self-renewal. We used a genome-wide approach to map binding
      patterns of PcG proteins (Pc, esc and Sce) in Drosophila melanogaster Kc cells.
      We found that Pc associates with large genomic regions of up to approximately 150
      kb in size, hereafter referred to as 'Pc domains'. Sce and esc accompany Pc in
      most of these domains. PcG-bound chromatin is trimethylated at histone H3 Lys27
      and is generally transcriptionally silent. Furthermore, PcG proteins
      preferentially bind to developmental genes. Many of these encode transcriptional
      regulators and key components of signal transduction pathways, including
      Wingless, Hedgehog, Notch and Delta. We also identify several new putative
      functions of PcG proteins, such as in steroid hormone biosynthesis. These results
      highlight the extensive involvement of PcG proteins in the coordination of
      development through the formation of large repressive chromatin domains.

PMID- 16628214
TI  - A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage
      sites.
AB  - The BRCA1 tumour suppressor and its heterodimeric partner BARD1 constitute an E3
      ubiquitin (Ub) ligase and function in DNA repair by unknown mechanisms. We show
      here that the Caenorhabditis elegans BRCA1/BARD1 (CeBCD) complex possesses an E3
      Ub ligase responsible for ubiquitylation at DNA damage sites following ionizing
      radiation (IR). The DNA damage checkpoint promotes the association of the CeBCD
      complex with E2-Ub conjugating enzyme, Ubc5(LET-70), leading to the formation of
      an active E3-Ub ligase on chromatin following IR. Correspondingly, defects in
      Ubc5(let-70) or the DNA damage checkpoint genes atl-1 or mre-11 abolish CeBCD
      dependent ubiquitylation in vivo. Extending these findings to human cells reveals
      a requirement for UbcH5c, the MRN complex, gamma-H2AX and a co-dependence for ATM
      and ATR kinases for BRCA1-dependent ubiquitylation at DNA damage sites.
      Furthermore, we demonstrate that the DNA damage checkpoint promotes the
      association between BRCA1 and UbcH5c to form an active E3-Ub ligase on chromatin
      after IR. These data reveal that BRCA1-dependent ubiquitylation is activated at
      sites of DNA repair by the checkpoint as part of a conserved DNA damage response.

PMID- 16628215
TI  - The FUSE/FBP/FIR/TFIIH system is a molecular machine programming a pulse of c-myc
      expression.
AB  - FarUpStream Element (FUSE) Binding Protein (FBP) binds the human c-myc FUSE in
      vitro only in single-stranded or supercoiled DNA. Because transcriptionally
      generated torsion melts FUSE in vitro even in linear DNA, and FBP/FBP Interacting
      Repressor (FIR) regulates transcription through TFIIH, these components have been
      speculated to be the mechanosensor (FUSE) and effectors (FBP/FIR) of a real-time
      mechanism controlling c-myc transcription. To ascertain whether the FUSE/FBP/FIR
      system operates according to this hypothesis in vivo, the flux of activators,
      repressors and chromatin remodeling complexes on the c-myc promoter was monitored
      throughout the serum-induced pulse of transcription. After transcription was
      switched on by conventional factors and chromatin regulators, FBP and FIR were
      recruited and established a dynamically remodeled loop with TFIIH at the P2
      promoter. In XPB cells carrying mutant TFIIH, loop formation failed and the serum
      response was abnormal; RNAi depletion of FIR similarly disabled c-myc regulation.
      Engineering FUSE into episomal vectors predictably re-programmed metallothionein
      promoter-driven reporter expression. The in vitro recruitment of FBP and FIR to
      dynamically stressed c-myc DNA paralleled the in vivo process.

PMID- 16628216
TI  - Regulating angiogenesis at the level of PtdIns-4,5-P2.
AB  - Angiogenesis is a coordinated sequence of cellular responses that result in the
      outgrowth of new blood vessels. The angiogenic program is regulated by
      extracellular factors, whose input is integrated at least in part at the level of
      signal transduction pathways driven by phosphoinositide 3 kinase (PI3K) and
      phospholipase Cgamma (PLCgamma). Using an in vitro angiogenesis model, we
      discovered that PI3K was essential for tube formation, whereas PLCgamma promoted
      regression. The underlying mechanism by which PLCgamma antagonized tube formation
      appeared to be by competing with PI3K for their common substrate,
      phosphatidylinositol-4,5-bisphosphate. These studies are the first to identify
      signaling enzymes involved with vessel regression, and reveal that the angiogenic
      program can be coordinated by the availability of a membrane lipid.

PMID- 16628217
TI  - Opaque cells signal white cells to form biofilms in Candida albicans.
AB  - Upon homozygosis from a/alpha to a/a or alpha/alpha, Candida albicans must still
      switch from the 'white' to 'opaque' phenotype to mate. It was, therefore,
      surprising to discover that pheromone selectively upregulated mating-associated
      genes in mating-incompetent white cells without causing G1 arrest or shmoo
      formation. White cells, like opaque cells, possess pheromone receptors, although
      their distribution and redistribution upon pheromone treatment differ between the
      two cell types. In speculating about the possible role of the white cell
      pheromone response, it is hypothesized that in overlapping white a/a and
      alpha/alpha populations in nature, rare opaque cells, through the release of
      pheromone, signal majority white cells of opposite mating type to form a biofilm
      that facilitates mating. In support of this hypothesis, it is demonstrated that
      pheromone induces cohesiveness between white cells, minority opaque cells
      increase two-fold the thickness of majority white cell biofilms, and majority
      white cell biofilms facilitate minority opaque cell chemotropism. These results
      reveal a novel form of communication between switch phenotypes, analogous to the
      inductive events during embryogenesis in higher eukaryotes.

PMID- 16628218
TI  - Phospholipase Cgamma/diacylglycerol-dependent activation of beta2-chimaerin
      restricts EGF-induced Rac signaling.
AB  - Although receptor-mediated regulation of small G-proteins and the cytoskeleton is
      intensively studied, the mechanisms for attenuation of these signals are poorly
      understood. In this study, we have identified the Rac-GAP beta2-chimaerin as an
      effector of the epidermal growth factor receptor (EGFR) via coupling to
      phospholipase Cgamma (PLCgamma) and generation of the lipid second messenger
      diacylglycerol (DAG). EGF redistributes beta2-chimaerin to promote its
      association with the small GTPase Rac1 at the plasma membrane, as determined by
      FRET. This relocalization and association with Rac1 were impaired by disruption
      of the beta2-chimaerin C1 domain as well as by PLCgamma1 RNAi, thus defining
      beta2-chimaerin as a novel DAG effector. On the other hand, GAP-deficient beta2
      chimaerin mutants show enhanced translocation and sustained Rac1 association in
      the FRET assays. Remarkably, RNAi depletion of beta2-chimaerin significantly
      extended the duration of Rac activation by EGF, suggesting that beta2-chimaerin
      serves as a mechanism that self-limits Rac activity in response to EGFR
      activation. Our results represent the first direct evidence of divergence in DAG
      signaling downstream of a tyrosine-kinase receptor via a PKC-independent
      mechanism.

PMID- 16628219
TI  - Interaction of Moloney murine leukemia virus matrix protein with IQGAP.
AB  - The matrix protein (MA) of the Moloney murine leukemia virus (M-MuLV) was found
      to interact with IQGAP1, a prominent regulator of the cytoskeleton. Mutational
      studies defined residues of MA critical for the interaction, and tests of viruses
      carrying MA mutations revealed a near-perfect correlation between binding and
      virus replication. The replication-defective mutants showed defects in both early
      and late stages of the life cycle. Four viable second-site revertant viruses were
      isolated from three different replication-defective parental mutants, and in all
      cases the interaction with IQGAP1 was restored by the suppressor mutations. The
      interaction of MA and IQGAP1 was readily detected in vitro and in vivo. Virus
      replication was potently inhibited by a C-terminal fragment of IQGAP1, and
      impaired by RNAi knockdown of IQGAP1 and 2. We suggest that the IQGAPs link the
      virus to the cytoskeleton for trafficking both into and out of the cell.

PMID- 16628220
TI  - Nucleotide flips determine the specificity of the Ecl18kI restriction
      endonuclease.
AB  - Restricion endonuclease Ecl18kI is specific for the sequence /CCNGG and cleaves
      it before the outer C to generate 5 nt 5'-overhangs. It has been suggested that
      Ecl18kI is evolutionarily related to NgoMIV, a 6-bp cutter that cleaves the
      sequence G/CCGGC and leaves 4 nt 5'-overhangs. Here, we report the crystal
      structure of the Ecl18kI-DNA complex at 1.7 A resolution and compare it with the
      known structure of the NgoMIV-DNA complex. We find that Ecl18kI flips both
      central nucleotides within the CCNGG sequence and buries the extruded bases in
      pockets within the protein. Nucleotide flipping disrupts Watson-Crick base
      pairing, induces a kink in the DNA and shifts the DNA register by 1 bp, making
      the distances between scissile phosphates in the Ecl18kI and NgoMIV cocrystal
      structures nearly identical. Therefore, the two enzymes can use a conserved DNA
      recognition module, yet recognize different sequences, and form superimposable
      dimers, yet generate different cleavage patterns. Hence, Ecl18kI is the first
      example of a restriction endonuclease that flips nucleotides to achieve
      specificity for its recognition site.

PMID- 16628221
TI  - pH-dependent conformational switch activates the inhibitor of transcription
      elongation.
AB  - Gfh1, a transcription factor from Thermus thermophilus, inhibits all catalytic
      activities of RNA polymerase (RNAP). We characterized the Gfh1 structure,
      function and possible mechanism of action and regulation. Gfh1 inhibits RNAP by
      competing with NTPs for coordinating the active site Mg2+ ion. This coordination
      requires at least two aspartates at the tip of the Gfh1 N-terminal coiled-coil
      domain (NTD). The overall structure of Gfh1 is similar to that of the Escherichia
      coli transcript cleavage factor GreA, except for the flipped orientation of the C
      terminal domain (CTD). We show that depending on pH, Gfh1-CTD exists in two
      alternative orientations. At pH above 7, it assumes an inactive 'flipped'
      orientation seen in the structure, which prevents Gfh1 from binding to RNAP. At
      lower pH, Gfh1-CTD switches to an active 'Gre-like' orientation, which enables
      Gfh1 to bind to and inhibit RNAP.

PMID- 16628222
TI  - Communication between subunits within an archaeal clamp-loader complex.
AB  - We have investigated the communication between subunits in replication factor C
      (RFC) from Archaeoglobus fulgidus. Mutation of the proposed arginine finger in
      the small subunits results in a complex that can still bind ATP but has impaired
      clamp-loading activity, a process that normally only requires binding of
      nucleotide. The small subunit alone forms a hexameric ring that is six-fold
      symmetric in the absence of ATP. However, this symmetry is broken when the
      nucleotide is bound to the complex. A conformational change associated with
      nucleotide binding may relate to the opening of PCNA rings by RFC during the
      loading reaction. The structures also reveal the importance of the N-terminal
      helix of each subunit at the ATP-binding site. Analysis of mutant protein
      complexes containing subunits lacking this N-terminal helix reveals key distinct
      regulatory roles during clamp loading that are different for the large and small
      subunits in the RFC complex.

PMID- 16628223
TI  - GIT2 represses Crk- and Rac1-regulated cell spreading and Cdc42-mediated focal
      adhesion turnover.
AB  - G protein-coupled receptor kinase interactors (GITs) regulate focal adhesion (FA)
      turnover, cell spreading, and motility through direct interaction with paxillin
      and the Rac-exchange factor Pak-interacting exchange factor beta (betaPIX).
      However, it is not clear whether GITs function to activate or repress motility or
      if the predominant GIT forms, GIT1 and GIT2, serve distinct or redundant roles.
      Here we demonstrate an obligatory role for endogenous GIT2 in repression of
      lamellipodial extension and FA turnover by Rac1- and Cdc42-dependent signaling
      pathways, respectively. Moreover, we show that the SH2-SH3 adaptor protein Crk is
      an essential target of GIT2 inhibition. Unexpectedly, we find that betaPIX is
      dispensable for the effects elicited by knockdown of GIT2. Finally, we show that
      loss of GIT2 is sufficient to induce migration of the nontransformed epithelial
      cell line MCF10A. These results suggest that inactivation of GIT2 function is a
      required step for induction of cell motility and that GIT2 may be a target of
      oncogenic signaling pathways that regulate cell migration.

PMID- 16628224
TI  - The length of the transcript encoded from the Kcnq1ot1 antisense promoter
      determines the degree of silencing.
AB  - The underlying mechanisms linking antisense RNA, chromatin architecture and gene
      expression have not been fully elucidated. Here we show that long transcripts
      encoded from the Kcnq1ot1 antisense promoter silence the flanking genes more
      efficiently than short antisense transcripts. Interestingly, the antisense RNA
      mediated deposition of inactive chromatin-specific histone modifications was
      higher with the longer antisense transcripts than with the shorter antisense
      transcripts. The kinetic studies of expression and chromatin remodeling of
      overlapping and nonoverlapping genes in response to antisense transcription
      revealed that the overlapping gene was rapidly silenced due to decrease in the
      occupancy of basal transcription machinery and simultaneous enrichment of its
      promoter with inactive chromatin modifications. The nonoverlapping gene,
      initially enriched with histone modifications specific to active chromatin, was
      subsequently silenced. Surprisingly, the flanking sequences were initially
      enriched with H3K9 monomethylation, as compared to di- and trimethylation, with a
      subsequent shift to trimethylated H3K9 enrichment. Our data provide a new
      perspective into antisense RNA-mediated gene silencing, and, more importantly,
      provide an explanation for why the antisense transcripts encoded from imprinting
      control regions are of significant length.

PMID- 16628225
TI  - Analysis of KaiA-KaiC protein interactions in the cyano-bacterial circadian clock
      using hybrid structural methods.
AB  - The cyanobacterial circadian clock can be reconstituted in vitro by mixing
      recombinant KaiA, KaiB and KaiC proteins with ATP, producing KaiC phosphorylation
      and dephosphorylation cycles that have a regular rhythm with a ca. 24-h period
      and are temperature-compensated. KaiA and KaiB are modulators of KaiC
      phosphorylation, whereby KaiB antagonizes KaiA's action. Here, we present a
      complete crystallographic model of the Synechococcus elongatus KaiC hexamer that
      includes previously unresolved portions of the C-terminal regions, and a negative
      stain electron microscopy study of S. elongatus and Thermosynechococcus elongatus
      BP-1 KaiA-KaiC complexes. Site-directed mutagenesis in combination with EM
      reveals that KaiA binds exclusively to the CII half of the KaiC hexamer. The EM
      based model of the KaiA-KaiC complex reveals protein-protein interactions at two
      sites: the known interaction of the flexible C-terminal KaiC peptide with KaiA,
      and a second postulated interaction between the apical region of KaiA and the ATP
      binding cleft on KaiC. This model brings KaiA mutation sites that alter clock
      period or abolish rhythmicity into contact with KaiC and suggests how KaiA might
      regulate KaiC phosphorylation.

PMID- 16628226
TI  - SUMO conjugation attenuates the activity of the gypsy chromatin insulator.
AB  - Chromatin insulators have been implicated in the establishment of independent
      gene expression domains and in the nuclear organization of chromatin. Post
      translational modification of proteins by Small Ubiquitin-like Modifier (SUMO)
      has been reported to regulate their activity and subnuclear localization. We
      present evidence suggesting that two protein components of the gypsy chromatin
      insulator of Dorsophila melanogaster, Mod(mdg4)2.2 and CP190, are sumoylated, and
      that SUMO is associated with a subset of genomic insulator sites. Disruption of
      the SUMO conjugation pathway improves the enhancer-blocking function of a
      partially active insulator, indicating that SUMO modification acts to regulate
      negatively the activity of the gypsy insulator. Sumoylation does not affect the
      ability of CP190 and Mod(mdg4)2.2 to bind chromatin, but instead appears to
      regulate the nuclear organization of gypsy insulator complexes. The results
      suggest that long-range interactions of insulator proteins are inhibited by
      sumoylation and that the establishment of chromatin domains can be regulated by
      SUMO conjugation.

PMID- 16628227
TI  - Induction of apoptosis in human lung cancer cells following treatment with
      amifostine and an adenoviral vector containing wild-type p53.
AB  - Adenoviral delivery of the p53 gene is a potential therapeutic approach for the
      treatment of lung cancer. Furthermore, amifostine is a cytoprotective agent and
      recent reports have described its potentiation of chemotherapy's antitumor
      activity in lung cancer. Therefore, we wished to investigate the ability of
      amifostine both alone and in combination with p53-based therapy to induce
      apoptosis, and to understand the mechanisms by which this apoptosis occurs. Using
      p53 null and wild-type p53 human lung cancer cells and normal human bronchial
      epithelial cells, we evaluated the effects of amifostine on proliferation and
      apoptosis. We then analyzed Adp53 in combination with amifostine and performed
      isobologram analysis. Expression of p53, p21(WAF1), Bax, Bak, bcl-2, as well as
      total and phosphorylated Cdc2 in the absence and presence of olomoucine, a
      phosphorylated Cdc2 kinase inhibitor, was then determined. Amifostine-induced
      apoptosis in human lung cancer cells in a dose-dependent fashion. The combination
      of amifostine and Adp53 significantly enhanced, with a supra-additive effect, the
      inhibition of proliferation of lung cancer cells. This enhancement of apoptosis
      by amifostine was associated with activation of p53 and dephosphorylation of Cdc2
      proteins. Notably, olomoucine effectively prevented amifostine and/or Adp53
      induced Cdc2 kinase activation and subsequent apoptosis. Our data shows that
      amifostine alone can induce apoptosis of human lung cancer cells, and that the
      combination of Adp53 with amifostine resulted in significantly higher levels of
      apoptosis. In addition, it appears that Cdc2 kinase plays an important role in
      the induction of apoptosis by amifostine and Adp53.

PMID- 16628228
TI  - Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal
      cancer correlates with tumor differentiation.
AB  - Modified adenoviruses represent a new approach to treatment of gastrointestinal
      cancer. However, their uptake by cells in many cases requires the major receptor
      for adenoviruses, the coxsackievirus and adenovirus receptor (CAR). Thus, lack of
      CAR expression is a potential cause of intrinsic resistance of tumor cells to
      this type of treatment. To evaluate this, we studied the localization of CAR
      protein in normal and malignant gastrointestinal tissues. In normal tissues, CAR
      was concentrated at sites of cell-cell interaction, in particular at the apico
      lateral cellular surface. Expression was particularly strong around bile and
      pancreatic ducts, which is in agreement with CAR's physiological function as a
      tight-junction protein. In GI malignancies (esophageal, pancreatic, colorectal
      and liver cancer), expression of the receptor varied substantially. Loss of CAR
      expression at cell-cell junction was evident in many samples. A significant
      correlation between CAR expression and histological grade was found, with
      moderately to poorly differentiated tumors most frequently demonstrating loss or
      reduction of CAR expression. These data indicate that CAR expression is
      frequently altered in gastrointestinal malignancy, potentially reducing the
      efficacy of adenovirus-based therapies.

PMID- 16628229
TI  - 13th Euroconference on apoptosis.

PMID- 16628230
TI  - Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with APPL
      during Drosophila development.
AB  - beta-Amyloid precursor protein binding protein 1 (APP-BP1) was previously
      identified based on its binding to the carboxyl terminal of beta-amyloid
      precursor protein. In this report, we have discovered that a mutation of dAPP-BP1
      (Drosophila ortholog of APP-BP1) hinders tissue development, causes apoptosis in
      imaginal disc cells, and blocks the NEDD8 conjugation pathway. We show that dAPP
      BP1 specifically binds the intracellular domain of APP-like protein (APPL). The
      dAPP-BP1 mutation partially suppresses the abnormal macrochaete phenotype of
      Appl(d), while overexpression of dAPP-BP1 causes abnormal macrochaetes. When APPL
      is overexpressed, the normal bristle pattern in the fly thorax is disturbed and
      apoptosis is induced in wing imaginal discs. APPL overexpression phenotypes are
      enhanced by reducing the level of dAPP-BP1. APPL overexpression is shown to
      inhibit the NEDD8 conjugation pathway. APPL-induced apoptosis is rescued by
      overexpression of dAPP-BP1. Our data suggest that APPL and dAPP-BP1 interact
      antagonistically during Drosophila development.

PMID- 16628231
TI  - Role of geminin: from normal control of DNA replication to cancer formation and
      progression?

PMID- 16628232
TI  - A new insight into phagocytosis of apoptotic cells: proteolytic enzymes divert
      the recognition and clearance of polymorphonuclear leukocytes by macrophages.
AB  - The recognition of phosphatidylserine (PS) on the surface of any apoptotic cell
      is considered to be a key event for its clearance. We challenge this concept by
      showing that pretreatment of neutrophils with either host or bacterial protease
      affects their uptake by human monocyte-derived macrophages without having an
      effect on cell-surface PS presentation. Specifically, whereas preincubation of
      apoptotic neutrophils with cathepsin G or thrombin significantly inhibited their
      uptake, gingipains R or clostripain enhanced phagocytosis by macrophages.
      Moreover, bacterial proteinases sensitized healthy neutrophils for uptake by
      macrophages, whereas endogenous proteinases were unable to elicit this effect.
      This stimulation was apparently owing to the combined effect of proteolytic
      cleavage of an antiphagocytic signal (CD31) and the generation of a novel 'eat
      me' signal on the neutrophil surface. These results argue that neutrophil
      recognition and phagocytosis by macrophages is mediated by a protein ligand whose
      proteolytic modification could affect the local inflammatory process.

PMID- 16628233
TI  - Activation of NF-kappaB by HDAC inhibitor apicidin through Sp1-dependent de novo
      protein synthesis: its implication for resistance to apoptosis.
AB  - Histone deacetylase (HDAC) inhibitors are promising anti-cancer drugs, but these
      exert differential responses depending on the cell types. Here, we demonstrate a
      new mechanism for activation of nuclear factor-kappaB (NF-kappaB) by HDAC
      inhibitor apicidin and the role of NF-kappaB signaling pathway for mediating
      differential cellular responses, especially, apoptosis. Treatment of HeLa cells
      with apicidin increases transcriptional activity of NF-kappaB and its target gene
      IL-8 and cIAP-1 induction, which involves the activation of IKK-IkappaBalpha
      signaling pathway through Sp1-dependent de novo protein synthesis. In parallel,
      apicidin treatment leads to histone hyperacetylation in the IL-8 promoter region
      independent of NF-kappaB signaling pathway, which is not sufficient for full
      transcription of IL-8 gene. This NF-kappaB activation contributes to resistance
      of HeLa cells to apoptotic potential of apicidin. Collectively, our results
      suggest that activation of NF-kappaB signaling cascade functions as a critical
      modulator to determine cell fate on apoptosis in response to HDAC inhibitors.

PMID- 16628234
TI  - Macrophages use different internalization mechanisms to clear apoptotic and
      necrotic cells.
AB  - The present study characterized two different internalization mechanisms used by
      macrophages to engulf apoptotic and necrotic cells. Our in vitro phagocytosis
      assay used a mouse macrophage cell line, and murine L929sAhFas cells that are
      induced to die in a necrotic way by TNFR1 and heat shock or in an apoptotic way
      by Fas stimulation. Scanning electron microscopy (SEM) revealed that apoptotic
      bodies were taken up by macrophages with formation of tight fitting phagosomes,
      similar to the 'zipper'-like mechanism of phagocytosis, whereas necrotic cells
      were internalized by a macropinocytotic mechanism involving formation of multiple
      ruffles directed towards necrotic debris. Two macropinocytosis markers (Lucifer
      Yellow (LY) and horseradish peroxidase (HRP)) were excluded from the phagosomes
      containing apoptotic bodies, but they were present inside the macropinosomes
      containing necrotic material. Wortmannin (phosphatidylinositol 3'-kinase (PI3K)
      inhibitor) reduced the uptake of apoptotic cells, but the engulfment of necrotic
      cells remained unaffected. Our data demonstrate that apoptotic and necrotic cells
      are internalized differently by macrophages.

PMID- 16628235
TI  - Linear pattern of West Nile virus-associated chorioretinitis is related to
      retinal nerve fibres organization.
AB  - PURPOSE: To clarify the reason for the linear pattern of West Nile virus (WNV)
      associated chorioretinitis. METHODS: The study included 12 patients (24 eyes)
      with WNV-associated chorioretinitis. All the patients underwent a complete
      ophthalmic evaluation, including dilated fundus examination, fundus photography,
      fluorescein angiography, and indocyanine green angiography. Characteristics of
      linear streaks, particularly their relationship to the course of retinal and
      choroidal vessels, and pattern of retinal nerve fibres, were analysed. RESULTS:
      All patients had bilateral multifocal chorioretinitis with linear clustering of
      chorioretinal lesions associated with a variable number of scattered lesions.
      Linear streaks, variable in number and length, originated from the optic disc or
      its vicinity in most cases. Their course in all cases appeared to closely follow
      the course of retinal nerve fibres, rather than that of retinal or choroidal
      vessels. CONCLUSIONS: Results of our study show that the linear pattern of WNV
      associated chorioretinitis is related to retinal nerve fibres organization,
      suggesting a contiguous spread of WNV virus from central nerve system via the
      optic nerve fibres to the outer retina, retinal pigment epithelium, and choroid.

PMID- 16628236
TI  - Reply to T Sandinha et al. Re: Superior forniceal conjunctival advancement
      pedicles (SFCAP) in the management of acute and impending corneal perforations.

PMID- 16628237
TI  - Decrease in reducing power of aqueous humor originating from glaucomatous
      rabbits.
AB  - AIM: To evaluate changes in the reducing power of aqueous humor (AH) with cyclic
      voltammetry (CV) and HPLC-EC. METHODS: NZW Rabbits exhibiting a sporadic mutation
      causing bilaterally buphthalmus eyes were set for intra ocular pressure (IOP) and
      eye size measurements. AH was obtained under anesthesia, from congenital
      glaucomatic rabbits (CGR, n=6) and age-matched controls (CON; n=6). The AH
      samples were analysed by CV and HPLC-EC. RESULTS: CGR IOP was found to be
      significantly higher than in CON (33.5+/-1.1 and 14.2+/-1.0 mmHg, respectively),
      eye size was 18.25 and 13.9 cm, respectively. CV analysis revealed two anodic
      currents representing two groups of low molecular weight antioxidant (LMWA). The
      two anodic potentials were equal for the two tested groups, indicating the same
      components of LMWA. The first anodic current of CGR was only 30% of the CON
      rabbits (2.11 vs7.17 microA/mg protein, t-test: P<0.05). As the main hydrophilic
      components of the first anodic current are known to be uric acid (UA) and
      ascorbic acid (AA), they were analysed for exact content by HPLC-EC. UA and AA
      levels were significantly lower in the CGR group (UA: 17.1+/-3.2 and 189.1+/
      75.70 microM/mg, AA: 1.1+/-0.3 and 4.8+/-2.0 microM/mg protein respectively).
      CONCLUSIONS: Changes in the reducing power, as indicated by CV analysis, of CGR
      AH, is probably a result of chronic oxidative stress caused by the pathology. The
      differences in the first anodic wave are mainly due to a fall in the
      concentration of UA and AA.

PMID- 16628238
TI  - Bilateral big-bag intraocular lens implant for highly myopic eyes.

PMID- 16628239
TI  - Long-term efficacy and visual acuity following transscleral diode laser
      photocoagulation in cases of refractory and non-refractory glaucoma.
AB  - AIMS: Transscleral diode laser cyclophotocoagulation (TSCP) is widely accepted in
      the treatment of refractory glaucoma especially in eyes with poor vision.
      However, until recently, there has been a reluctance to extend its use to eyes
      with good visual acuity (VA). The aims of this study were to evaluate the long
      term efficacy and safety of TSCP for a range of glaucoma conditions, with
      particular emphasis on post-treatment VA in seeing eyes. METHODS: A retrospective
      analysis of case notes of 74 treated eyes was conducted over a period of 4-30
      months (mean 12.5 months). RESULTS: Mean (SD) intraocular pressure (IOP) was
      reduced by 43% from 40.3 (6.7) to 21.1 mmHg (5.4) at the final index visit. Of
      all patients, 58% had a reduction in glaucoma drops and all discontinued oral
      Acetazolamide; 9% experienced complications. Mean VA was preserved in the
      subgroups with good vision, although 3/23 (13%) patients with primary open-angle
      glaucoma (POAG) lost vision due to cataract and glaucoma progression. There were
      no cases of hypotony (IOP<or=5 mmHg) or phthisis and only one eye required re
      treatment. CONCLUSIONS: TSCP is highly effective and safe for various types of
      glaucoma, and its use can be extended to eyes with good vision.

PMID- 16628240
TI  - Retinal diseases in Ibadan.

PMID- 16628241
TI  - Macular hole secondary to X-linked retinoschisis.

PMID- 16628242
TI  - Comparison of Luneau SA disposable and Goldmann applanation tonometer readings.
AB  - PURPOSE: To test the agreement of intraocular pressure (IOP) measurements made
      with Luneau SA applanators and Goldmann applanator. MATERIALS AND METHODS: A
      single-blind crossover trial. IOPs were measured in both eyes of subjects with
      both applanators. Type of applanator was alternated to eliminate systematic bias.
      Multiple observers were used. Observers were blind to the scale while performing
      measurements but not to the type of applanator used. The appearance of the
      meniscus was assessed semiquantitatively. All measurements were combined and
      presented in a Bland-Altman plot. RESULTS: A total of 140 eyes of 79 subjects
      were tested by seven observers. The range of measurements was 6-45 mmHg (mean
      17.8 mmHg) for the Goldmann applanator. On average, the Luneau SA applanator
      (range of measurements 4-36 mmHg) gave a measurement of 2.35 mmHg less than the
      Goldmann standard. The standard deviation of these differences was 2.13 mmHg,
      giving an upper 95% confidence limit of 6.53 mmHg and a lower 95% confidence
      limit of -1.83 mmHg. The measurements agreed in only 24 out of 140 instances. In
      28 eyes, the disposable tonometer end point was difficult to assess owing to
      excessively thick rings. Linear extrapolation suggests an increase in difference
      with increasing IOP. CONCLUSION: The inter-head inaccuracy, tendency to
      underestimate IOP, and lack of systematic inaccuracy make a corrective algorithm
      impossible to formulate. The range of variation between the Luneau SA disposable
      applanator and the Goldmann standard is sufficiently large to influence clinical
      management decisions. We speculate that one explanation is the interaction of the
      tonometer with the tear film, making end point determination difficult. Further
      research is being undertaken.

PMID- 16628243
TI  - Intraoperative breakage of the mushroom manipulator tip during
      phacoemulsification.

PMID- 16628244
TI  - Dynamics of ocular surface topography.
AB  - PURPOSE: To investigate fluctuations in the ocular surface, we used high-speed
      videokeratoscopy (50 Hz) to measure the dynamics of the ocular surface
      topography. METHODS: Ocular surface height difference maps were computed to
      illustrate the changes in the tear film in the inter-blink interval. Topography
      data were used to derive the ocular surface wavefront aberrations up to the
      fourth radial order of the Zernike polynomial expansion. We examined the ocular
      surface dynamics and temporal changes in the ocular surface wavefront aberrations
      in the inter-blink interval. RESULTS: During the first 0.5 s following a blink,
      the ocular surface height at the upper edge of the topography map increased by
      about 2 mum. Temporal changes occurred for some ocular surface wavefront
      aberrations and appeared to be related to changes in the distribution of tear
      film. CONCLUSION: In the clinical measurement of ocular surface topography using
      videokeratoscopy or optics of the eye using wavefront sensors, care should be
      taken to avoid the initial tear film build-up phase following a blink to achieve
      more consistent results.

PMID- 16628245
TI  - NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB
      126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies).
AB  - DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic
      hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability
      to bind to and activate the ligand-activated transcription factor, the aryl
      hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR
      and exhibit biological actions similar to TCDD are commonly referred to as
      "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the
      ingestion of foods containing residues of DLCs that bioconcentrate through the
      food chain. Due to their lipophilicity and persistence, once internalized they
      accumulate in adipose tissue resulting in chronic lifetime human exposure. Since
      human exposure to DLCs always occurs as a complex mixture, the Toxic Equivalency
      Factor (TEF) methodology has been developed as a mathematical tool to assess the
      health risk posed by complex mixtures of these compounds. The TEF methodology is
      a relative potency scheme that ranks the dioxin-like activity of a compound
      relative to TCDD that is the most potent congener. This allows for the estimation
      of the potential dioxin-like activity of a mixture of chemicals, based on a
      common mechanism of action involving an initial binding of DLCs to the AhR. The
      toxic equivalency of DLCs was nominated for evaluation, because of the widespread
      human exposure to DLCs and the lack of data on the adequacy of the TEF
      methodology for predicting relative potency for cancer risk. To address this, the
      National Toxicology Program conducted a series of 2-year bioassays in female
      Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity
      of DLCs and structurally-related polychlorinated biphenyls (PCBs) and mixtures of
      these compounds. 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) was produced
      commercially before 1977 for the electric industry as a dielectric insulating
      fluid for transformers and capacitors. Manufacture and use of the chemical was
      stopped because of increased PCB residues in the environment, but it continues to
      be released into the environment through the use and disposal of products
      containing PCBs, as by-products during the manufacture of certain organic
      chemicals, and during combustion of some waste materials. Bioaccumulation of PCB
      126 results in persistent levels in animal and human tissues and the biological
      responses to PCB 126 are similar to those of TCDD, a known human carcinogen. PCB
      126 was selected for study by the National Toxicology Program as a part of the
      dioxin TEF evaluation to assess the cancer risk posed by complex mixtures of
      polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and PCBs. The dioxin TEF evaluation includes conducting multiple 2-year rat
      bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs,
      structurally related PCBs, and mixtures of these compounds. PCB 126 was included
      since this is the most potent coplanar PCB that has dioxin-like activities. While
      one of the aims of the dioxin TEF evaluation was a comparative analysis across
      studies, in this Technical Report only the results of the PCB 126 study are
      presented and discussed. Female Harlan Sprague-Dawley rats were administered PCB
      126 (99% pure) in corn oil with acetone by gavage for 14, 31, or 53 weeks or 2
      years. 2-YEAR STUDY: Groups of 81 female rats were administered 30, 100, 175,
      300, 550, or 1,000 ng PCB 126/kg body weight in corn oil:acetone (99:1) by
      gavage, 5 days per week, for up to 104 weeks; a group of 81 vehicle control
      female rats received the corn oil/acetone vehicle alone. A group of 28 rats
      received 10 ng/kg for up to 53 weeks only. Up to 10 rats per group were evaluated
      at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered
      1,000 ng/kg PCB 126 in corn oil:acetone (99:1) by gavage for 30 weeks then the
      vehicle for the remainder of the study. Mean body weights of 30 and 100 ng/kg
      rats were similar to those of the vehicle controls during most of the study, mean
      body weights of 175 and 300 ng/kg rats were less than those of the vehicle
      controls during year 2 of the study, and mean body weights of 550 ng/kg, 1,000
      ng/kg core study, and 1,000 ng/kg stop-exposure rats were less than those of the
      vehicle controls after week 17. THYROID HORMONE CONCENTRATIONS: Alterations in
      serum thyroid hormone levels were evaluated at the 14-, 31- and 53- week interim
      evaluations. In the 550 and 1,000 ng/kg rats, total thyroxine (T4) and free T4
      were significantly lower than vehicle controls and serum triiodothyronine (T3)
      and thyroid stimulating hormone (TSH) levels were significantly higher than
      vehicle controls at the 14-week interim evaluation. Serum T3 was also
      significantly higher in the 300 ng/kg rats compared to vehicle controls at 14
      weeks. At 31 weeks, T3 was significantly higher at doses of 100 ng/kg or greater
      compared to vehicle controls. TSH levels were higher in 550 and 1,000 ng/kg rats
      than in vehicle controls. At 53 weeks, significantly lower serum concentrations
      of total T4 and free T4 were observed compared to vehicle controls in groups
      administered 175 ng/kg or greater and 30 ng/kg or greater, respectively. Serum T3
      levels were significantly higher at doses of 175 ng/kg or greater compared to
      vehicle controls. No changes in TSH were observed between vehicle controls and
      dosed rats at 53 weeks. HEPATIC CELL PROLIFERATION DATA: To evaluate hepatocyte
      replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'
      deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations. The
      hepatocellular labeling index was significantly higher at doses of 300 ng/kg or
      greater at 14 weeks and 175 ng/kg or greater at 31 weeks compared to vehicle
      controls. No statistically significant differences were observed between vehicle
      controls and PCB 126 dosed rats at 53 weeks. However at 53 weeks, a 5.8-fold
      increase above the vehicle controls was observed in the 1,000 ng/kg group.
      CYTOCHROME P450 ENZYME ACTIVITIES: To evaluate the expression of known dioxin
      responsive genes, CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD)
      activity and CYP1A2-associated acetanilide 4-hydroxylase (A-4-H) activity were
      evaluated at the 14-, 31-, and 53-week interim evaluations. In addition, CYP2B
      associated pentoxyresorufin-O-deethylase (PROD) activity was also analysed.
      Hepatic PROD (CYP2B1) and hepatic and pulmonary EROD (CYP1A1) activity were
      significantly greater in all dosed groups than in vehicle controls at weeks 14,
      31, and 53. Hepatic A-4-H (CYP1A2) activity was significantly greater in the 30,
      100, 175, 300, 550, and 1,000 ng/kg groups compared to vehicle controls at weeks
      14, 31, and 53. DETERMINATIONS of PCB 126 CONCENTRATIONS IN TISSUES: The tissue
      disposition of PCB 126 was analyzed in the liver, lung, fat, and blood of all
      rats in vehicle controls and all dosed groups at the 14-, 31-, and 53-week
      interim evaluations and in 10 rats per group including vehicle controls at the
      end of the 2-year study (104 weeks). Detectable concentrations of PCB 126 were
      observed in the liver, fat, lung, and blood. Measurable concentrations of PCB 126
      were present in the liver and fat at weeks 31, 53, and 104. Hepatic and fat
      concentrations increased with increasing doses of PCB 126. Measurable
      concentrations of PCB 126 were present in vehicle control lung tissue at 53 and
      104 weeks. No PCB 126 was observed in the blood from the vehicle control rats.
      Lung and blood concentrations tended to increase with increasing doses of PCB
      126, with a few exceptions. In the stop-exposure group, PCB 126 concentrations in
      liver and fat were lower than the levels observed in the 30 ng/kg group. In the
      stop-exposure group, lung tissue PCB 126 concentrations were equivalent to the
      levels observed in the 30 ng/kg group. In blood from the stop-exposure group, PCB
      126 concentrations were equivalent to the levels observed in the 100 ng/kg group.
      PATHOLOGY AND STATISTICAL ANALYSES: Absolute and relative liver weights were
      significantly increased at all time points and correlated with increased
      incidences of hepatocellular hypertrophy. At 2 years, there were significant
      treatment-related increases in the incidences of cholangiocarcinoma and
      hepatocellular adenoma. Three hepatocholangiomas were seen in the 1,000 ng/kg
      core study group and a single incidence of cholangioma each occurred in the 550
      and 1,000 ng/kg core study groups. At 2 years, a significant dose-related
      increase in hepatic toxicity was observed and was characterized by increased
      incidences of numerous lesions including hepatocyte hypertrophy, multinucleated
      hepatocytes, diffuse fatty change, bile duct hyperplasia, bile duct cyst, oval
      cell hyperplasia, necrosis, pigmentation, inflammation, nodular hyperplasia,
      portal fibrosis, cholangiofibrosis, and toxic hepatopathy. The incidences of
      these lesions were generally decreased in the 1,000 ng/kg stop-exposure group
      compared to the 1,000 ng/kg core study group. The lung weights of 1,000 ng/kg
      rats were generally significantly increased at weeks 14, 31, and 53. At 2 years,
      treatment related increases in the incidences of cystic keratinizing epithelioma
      and squamous cell carcinomas were observed. In addition, dose-related increases
      in the incidences of bronchiolar metaplasia of the alveolar epithelium and
      squamous metaplasia were also observed. The incidence of gingival squamous cell
      carcinoma of the oral mucosa was significantly increased in the 1,000 ng/kg core
      study group at 2 years. Gingival squamous cell carcinoma, although reduced in
      incidence as compared to the 1,000 ng/kg core study group, was still present in
      the 1,000 ng/kg stop-exposure group. At 2 years, adenomas and/or carcinomas were
      present in the adrenal cortex of most core study groups and in the 1,000 ng/kg
      stop-exposure group. Dose-related effects on the incidences of adrenal cortex
      atrophy and cytoplasmic vacuolization were also seen. (ABSTRACT TRUNCATED)

PMID- 16628246
TI  - Loss of Atrx affects trophoblast development and the pattern of X-inactivation in
      extraembryonic tissues.
AB  - ATRX is an X-encoded member of the SNF2 family of ATPase/helicase proteins
      thought to regulate gene expression by modifying chromatin at target loci.
      Mutations in ATRX provided the first example of a human genetic disease
      associated with defects in such proteins. To better understand the role of ATRX
      in development and the associated abnormalities in the ATR-X (alpha thalassemia
      mental retardation, X-linked) syndrome, we conditionally inactivated the homolog
      in mice, Atrx, at the 8- to 16-cell stage of development. The protein, Atrx, was
      ubiquitously expressed, and male embryos null for Atrx implanted and gastrulated
      normally but did not survive beyond 9.5 days postcoitus due to a defect in
      formation of the extraembryonic trophoblast, one of the first terminally
      differentiated lineages in the developing embryo. Carrier female mice that
      inherit a maternal null allele should be affected, since the paternal X
      chromosome is normally inactivated in extraembryonic tissues. Surprisingly,
      however, some carrier females established a normal placenta and appeared to
      escape the usual pattern of imprinted X-inactivation in these tissues. Together
      these findings demonstrate an unexpected, specific, and essential role for Atrx
      in the development of the murine trophoblast and present an example of escape
      from imprinted X chromosome inactivation.

PMID- 16628247
TI  - Conformational changes in protein loops and helices induced by post-translational
      phosphorylation.
AB  - Post-translational phosphorylation is a ubiquitous mechanism for modulating
      protein activity and protein-protein interactions. In this work, we examine how
      phosphorylation can modulate the conformation of a protein by changing the energy
      landscape. We present a molecular mechanics method in which we phosphorylate
      proteins in silico and then predict how the conformation of the protein will
      change in response to phosphorylation. We apply this method to a test set
      comprised of proteins with both phosphorylated and non-phosphorylated crystal
      structures, and demonstrate that it is possible to predict localized
      phosphorylation-induced conformational changes, or the absence of conformational
      changes, with near-atomic accuracy in most cases. Examples of proteins used for
      testing our methods include kinases and prokaryotic response regulators. Through
      a detailed case study of cyclin-dependent kinase 2, we also illustrate how the
      computational methods can be used to provide new understanding of how
      phosphorylation drives conformational change, why substituting Glu or Asp for a
      phosphorylated amino acid does not always mimic the effects of phosphorylation,
      and how a phosphatase can "capture" a phosphorylated amino acid. This work
      illustrates how computational methods can be used to elucidate principles and
      mechanisms of post-translational phosphorylation, which can ultimately help to
      bridge the gap between the number of known sites of phosphorylation and the
      number of structures of phosphorylated proteins.

PMID- 16628248
TI  - Identification and classification of conserved RNA secondary structures in the
      human genome.
AB  - The discoveries of microRNAs and riboswitches, among others, have shown
      functional RNAs to be biologically more important and genomically more prevalent
      than previously anticipated. We have developed a general comparative genomics
      method based on phylogenetic stochastic context-free grammars for identifying
      functional RNAs encoded in the human genome and used it to survey an eight-way
      genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra
      fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose
      threshold for acceptance, this search resulted in a set of 48,479 candidate RNA
      structures. This screen finds a large number of known functional RNAs, including
      195 miRNAs, 62 histone 3'UTR stem loops, and various types of known genetic
      recoding elements. Among the highest-scoring new predictions are 169 new miRNA
      candidates, as well as new candidate selenocysteine insertion sites, RNA editing
      hairpins, RNAs involved in transcript auto regulation, and many folds that form
      singletons or small functional RNA families of completely unknown function. While
      the rate of false positives in the overall set is difficult to estimate and is
      likely to be substantial, the results nevertheless provide evidence for many new
      human functional RNAs and present specific predictions to facilitate their
      further characterization.

PMID- 16628249
TI  - Tropical Medicine and Animal Diseases: Onderstepoort and the Development of
      Veterinary Science in South Africa 1908-1950.
AB  - This article traces the development of agricultural science at the Onderstepoort
      Veterinary Institute, near Pretoria, from its founding in 1908 until the 1950s,
      by which time many enzootic and epizootic diseases had either been eradicated, or
      were largely controllable through various forms of prophylaxis. The Institute
      demonstrated the political and economic significance attributed to the pastoral
      industry in South Africa and the conviction that scientific discoveries could
      increase output. During this period, researchers explicated the aetiology and
      provenance of hitherto mysterious diseases such as lamsiekte, geeldikkop and
      African horsesickness. They developed vaccines, some of which were adopted
      internationally. The nature of their investigations showed that veterinary
      science increasingly entailed more than just progress in biomedical procedures.
      Ecological factors, in particular the nutritional state of the veld, became a
      priority from the 1920s onwards as veterinarians saw their function as promoting
      animal health as well as eliminating disease. Dealing with contagious infections
      also incorporated less welcome, and at times controversial, approaches to disease
      control. The imposition of pastoral regulations illustrated the expanding powers
      of the South African state, founded on presumptions of scientific legitimacy. The
      article also explores the contribution made by African communities and settler
      farmers to the institutionalisation of veterinary knowledge, as well as the role
      South African researchers played in the evolution of a colonial, as well as an
      increasingly international, scientific culture.

PMID- 16628250
TI  - Classroom Interpreting and Visual Information Processing in Mainstream Education
      for Deaf Students: Live or Memorex?
AB  - This study examined visual information processing and learning in classrooms
      including both deaf and hearing students. Of particular interest were the effects
      on deaf students' learning of live (three-dimensional) versus video-recorded (two
      dimensional) sign language interpreting and the visual attention strategies of
      more and less experienced deaf signers exposed to simultaneous, multiple sources
      of visual information. Results from three experiments consistently indicated no
      differences in learning between three-dimensional and two-dimensional
      presentations among hearing or deaf students. Analyses of students' allocation of
      visual attention and the influence of various demographic and experimental
      variables suggested considerable flexibility in deaf students' receptive
      communication skills. Nevertheless, the findings also revealed a robust advantage
      in learning in favor of hearing students.

PMID- 16628251
TI  - Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise
      interaction of CD2AP, Fyn, and synaptopodin.
AB  - Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular
      diagnosis resulting in end-stage renal disease. Defects in several podocyte
      proteins have been implicated in the etiology of FSGS, including podocin, alpha
      actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing
      understanding of genes involved in the pathogenesis of focal segmental sclerosis,
      the vast majority of patients with this disease, even those with a familial
      linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of
      genetic heterozygosity (bigenic heterozygosity) that alone do not result in
      clinical kidney disease could function together to enhance susceptibility to
      glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and
      heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not
      kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like
      glomerular damage. These genetic interactions were also reflected at a functional
      level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1.
      This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that
      combined mutations in 2 or multiple podocyte genes may be a common etiology for
      glomerular disease.

PMID- 16628252
TI  - Mast cell IL-4 expression is regulated by Ikaros and influences encephalitogenic
      Th1 responses in EAE.
AB  - When exposed to a pathogen, a naive CD4(+) T cell is forced to make a cell fate
      decision that leads to a polarized population of Th1 IFN-gamma- or Th2 IL-4-
      producing cells. Although IL-4 has traditionally been considered a factor that
      promotes Th2 cell differentiation, recent evidence has demonstrated that the site
      and timing of IL-4 expression in an immune response determines its ultimate
      effects on CD4(+) T cell fate. Using a mast cell (MC) reconstitution model, we
      demonstrate that MC-derived IL-4 promoted Th1 responses in vivo. Furthermore, MCs
      from genetically disparate mouse strains varied in their potential for IL-4
      expression. Independent of the activation mode, MCs from Th1-prone C57BL/6 mice
      exhibited a more robust Il4 response than did the Th2-prone strain Balb/c. The
      hierarchy of IL-4 expression potential was directly associated with the degree of
      basal chromatin accessibility at cis-regulatory elements conserved noncoding
      sequence-1 and V(A) enhancer within the Th2 locus. GATA1/2 and Ikaros, factors
      with opposing roles in chromatin remodeling, acted at these sites. We propose
      that GATA and Ikaros proteins coordinately fine-tune accessibility at the Il4
      locus during development to variably regulate IL-4 expression. These events
      likely contribute to the genetically determined heterogeneity in Th1 responses
      that underlie susceptibility to many diseases.

PMID- 16628253
TI  - Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent
      onset autoimmune diabetes by inducing Tregs.
AB  - Safe induction of autoantigen-specific long-term tolerance is the "holy grail"
      for the treatment of autoimmune diseases. In animal models of type 1 diabetes,
      oral or i.n. immunization with islet antigens induces Tregs that are capable of
      bystander suppression. However, such interventions are only effective early in
      the prediabetic phase. Here, we demonstrate that a novel combination treatment
      with anti-CD3epsilon-specific antibody and i.n. proinsulin peptide can reverse
      recent-onset diabetes in 2 murine diabetes models with much higher efficacy than
      with monotherapy with anti-CD3 or antigen alone. In vivo, expansion of
      CD25(+)Foxp3(+) and insulin-specific Tregs producing IL-10, TGF-beta, and IL-4
      was strongly enhanced. These cells could transfer dominant tolerance to
      immunocompetent recent-onset diabetic recipients and suppressed heterologous
      autoaggressive CD8 responses. Thus, combining a systemic immune modulator with
      antigen-specific Treg induction is more efficacious in reverting diabetes. Since
      Tregs act site-specifically, this strategy should also be expected to reduce the
      potential for systemic side effects.

PMID- 16628254
TI  - Connexin 26 regulates epidermal barrier and wound remodeling and promotes
      psoriasiform response.
AB  - Inflammatory skin disorders result in significant epidermal changes, including
      keratinocyte hyperproliferation, incomplete differentiation, and impaired
      barrier. Here we test whether, conversely, an impaired epidermal barrier can
      promote an inflammatory response. Mice lacking the transcription factor Kruppel
      like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition.
      Transcription profiling of Klf4(-/-) newborn skin revealed similar changes in
      gene expression to involved psoriatic plaques, including a significant
      upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression
      of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26)
      demonstrated that downregulation of Cx26 is required for barrier acquisition
      during development. In juvenile and adult mice, persistent Cx26 expression kept
      wounded epidermis in a hyperproliferative state, blocked the transition to
      remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic
      expression of Cx26 in keratinocytes resulted in increased ATP release, which
      delayed epidermal barrier recovery and promoted an inflammatory response in
      resident immune cells. These results provide a molecular link between barrier
      acquisition in utero and epidermal remodeling after wounding. More generally,
      these studies suggest that the most effective treatments for inflammatory skin
      disorders might concomitantly suppress the immune response and enhance epidermal
      differentiation to restore the barrier.

PMID- 16628255
TI  - Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in
      NOD mice.
AB  - Factors that determine the spectrum of target organs involved in autoimmune
      destruction are poorly understood. Although loss of function of autoimmune
      regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the
      pathogenic roles of AIRE in regulating target-organ specificity remain elusive.
      In order to gain insight into this issue, we have established NOD mice, an animal
      model of type 1 diabetes caused by autoimmune attack against beta cell islets, in
      which Aire has been abrogated. Remarkably, acinar cells rather than beta cell
      islets were the major targets of autoimmune destruction in Aire-deficient NOD
      mice, and this alteration of intra-pancreatic target-organ specificity was
      associated with production of autoantibody against pancreas-specific protein
      disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells.
      Consistent with this pathological change, the animals were resistant to the
      development of diabetes. The results suggest that Aire not only is critical for
      the control of self-tolerance but is also a strong modifier of target-organ
      specificity through regulation of T cell repertoire diversification. We also
      demonstrated that transcriptional expression of PDIp was retained in the Aire
      deficient NOD thymus, further supporting the concept that Aire may regulate the
      survival of autoreactive T cells beyond transcriptional control of self-protein
      expression in the thymus.

PMID- 16628256
TI  - Tesaglitazar: a promising approach in type 2 diabetes.
AB  - While glycemic control remains the cornerstone of clinical management for
      patients with type 2 diabetes, the importance of a more comprehensive approach
      that addresses the multiple metabolic abnormalities seen in this population is
      now widely recognized. Abnormal lipid metabolism resulting in dyslipidemia
      contributes greatly to the markedly increased risks of cardiovascular disease
      observed in diabetic patients and in prediabetic patients with signs of insulin
      resistance. The peroxisome proliferator-activated receptors (PPARs) play a key
      role in the regulation of energy homeostasis and the coordination of inflammatory
      responses. As such, they are interesting targets for addressing both the glucose
      and lipid abnormalities associated with insulin resistance. The
      thiazolidinediones (TZDs), which activate PPARgamma, appear to improve glycemic
      control primarily by increasing peripheral insulin sensitivity and reducing
      hepatic glucose production, thereby helping to preserve beta-cell function. They
      have also demonstrated modest beneficial effects on some lipid parameters. The
      fibrate drugs, which activate PPARalpha, produce robust improvements in
      dyslipidemia, decrease atherosclerotic lesions and may have an effect on
      cardiovascular events, but do not affect glycemia. Theoretically, a compound
      targeting both the alpha and gamma PPARs simultaneously might combine the
      benefits of TZDs and fibrates. Tesaglitazar is a dual-acting PPARalpha/gamma
      agonist currently being investigated in phase III clinical trials as an
      alternative treatment for insulin resistance and the characteristic dyslypidemia
      of type 2 diabetes. This article reviews the available data on the clinical
      efficacy and safety of tesaglitazar in patients with type 2 diabetes and in
      individuals without diabetes but with insulin resistance.

PMID- 16628257
TI  - Clinical experience with erlotinib in non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer death worldwide. Despite the
      introduction of more- effective chemotherapeutic agents, it appears that a
      survival plateau has been reached, so new treatment strategies are clearly
      needed. One innovative therapeutic cancer strategy is the introduction of
      biological agents that target specific intracellular pathways related to the
      distinctive properties of cancer cells. Among these agents, epidermal growth
      factor receptor (EGFR)-targeting agents have received particular attention in
      lung cancer. Numerous EGFR blockers have been evaluated, including monoclonal
      antibodies to the receptor and small-molecule tyrosine kinase inhibitors. The
      present review focuses on the tyrosine kinase inhibitor erlotinib. Preclinical
      studies have shown that erlotinib blocks the growth of human non-small-cell lung
      cancer (NSCLC) cell lines in vitro by inhibiting the receptor and the downstream
      protein phosphorylation. In a randomized study conducted by the National Cancer
      Institute of Canada (BR.21) in second- and third-line NSCLC treatment, erlotinib
      significantly prolonged overall survival and decreased symptoms compared with
      placebo. A crucial aspect of the clinical development of molecular-targeted
      therapies is to understand which patients will obtain clinical benefit from their
      use. Sensitivity to erlotinib has been associated with EGFR mutations, most
      commonly deletions of four to six amino acids in exon 19 or a point mutation
      (L858R) in exon 21. Increased EGFR gene copy number has also been pointed out as
      a good predictive marker for erlotinib response. Intense research activity is
      ongoing to validate known predictive markers and to discover new tools which
      maximize clinical benefit using erlotinib. However, there is no conclusive
      evidence, as yet, linking response to survival.

PMID- 16628258
TI  - A single-pill combination of amlodipine besylate and atorvastatin calcium.
AB  - This review describes the clinical profile and rationale for the development of a
      single-pill formulation of the calcium channel blocker amlodipine besylate, a
      blood pressure-lowering agent with pleiotropic effects, and atorvastatin calcium,
      a statin with lipid-lowering as well as pleiotropic anti-atherosclerotic
      properties. Amlodipine and atorvastatin have been demonstrated in numerous
      clinical trials to be highly effective in lowering blood pressure and low-density
      lipoprotein cholesterol (LDL-C). Furthermore, both amlodipine and atorvastatin
      have been demonstrated to reduce cardiovascular events in a broad range of
      patients. The amlodipine/atorvastatin single pill has been shown to improve
      patients' achievement of national guideline-recommended blood pressure and lipid
      target levels and exhibits a safety profile consistent with its parent compounds.
      The combination pill is available in formulations appropriate for administration
      across therapeutic dose ranges targeted to a wide variety of hypertensive
      patients with additional risk factors and differing degrees of cardiovascular
      risk, or with manifest cardiovascular disease. Single-pill
      amlodipine/atorvastatin has the potential to improve the management of
      hypertensive patients with additional cardiovascular risk factors, especially
      dyslipidemia, by reducing pill burden and prescription costs. This potential has
      important implications because hypertensive patients with additional risk factors
      represent a large proportion of those at risk for cardiovascular events.

PMID- 16628259
TI  - Ranolazine: focusing on angina pectoris.
AB  - Chronic stable angina is common and is a difficult-to-manage problem when
      patients begin to fail conventional therapy especially when maximal
      revascularization has been provided. The most promising agent in development is
      ranolazine, a late sodium channel inhibitor and partial fatty oxidation inhibitor
      which has unique and desirable anti-ischemic and electrophysiologic properties.
      This agent is likely to become standard therapy for chronic stable angina and may
      play a future role in the management of acute coronary syndromes.

PMID- 16628260
TI  - Olanzapine/fluoxetine combination for bipolar depression and other mood
      disorders: a review.
AB  - Patients with bipolar disorder tend to experience most of their illness in the
      depressed phase. Existing antidepressant therapies are effective in bipolar
      depression but carry a risk of treatment-emergent mania or increased phase
      cycling. Other therapies such as lithium may not be particularly effective, or
      may not currently be licensed for the acute phase, such as lamotrigine. A
      combination of the antipsychotic olanzapine and the serotonin reuptake inhibitor
      fluoxetine has been investigated in both bipolar depression and other affective
      disorders such as psychotic depression and treatment-refractory depression. The
      combination's possible mode of action, pharmacokinetics, drug interactions,
      clinical efficacy and safety and tolerability have been reviewed.

PMID- 16628261
TI  - Gene therapy for ulcerations of the gastrointestinal tract.
AB  - Ulcer healing requires cell proliferation, migration (re-epithelialization) and
      angiogenesis - all ultimately leading to scar formation. All these processes are
      controlled by growth factors. Gene therapy has shown only limited promise for
      effective treatment of congenital diseases. This is due to time-limited gene
      expression, adverse immune responses and/or complications related to viral
      vectors. However, short- term expression of genes encoding angiogenic growth
      factors appears to be ideal for treatment of chronic ulcers and wounds, which
      require only limited temporal gene overexpression. Since angiogenesis is
      essential for wound and ulcer healing, the genes encoding proangiogenic growth
      factors have been utilized for treatment of experimental esophageal, gastric and
      duodenal ulcers. These studies demonstrated that a single local injection of
      plasmids expressing vascular endothelial growth factor and angiopoietin-1
      dramatically accelerates the healing of duodenal, gastric and esophageal gastric
      ulcers. Preliminary data indicate that such treatment can also be effective for
      the healing of experimental colitis.

PMID- 16628262
TI  - Pathophysiology of interleukin-23 in experimental autoimmune encephalomyelitis.
AB  - Interleukin-23 (IL-23) is a heterodimeric cytokine that is composed of a p40
      subunit, shared with the closely related cytokine IL-12, and a smaller IL-23p19
      subunit. It belongs to a family of heterodimeric cytokines that also includes IL
      12 and IL-27. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune
      disease that serves as a model for multiple sclerosis, an inflammatory
      demyelinating disease of the central nervous system that is a frequent cause of
      disability in young adults. EAE is thought to be initiated by CD4+ T cells. The
      production of interferon-gamma and tumor necrosis factor-alpha (T helper 1 [Th1]
      phenotype) was considered a marker for the ability of such cells to induce
      disease. Consistent with this view, IL-12, a cytokine that induces the
      differentiation of Th1 cells, was considered essential for EAE susceptibility.
      However, it is now clear that IL-23 rather than IL-12 is required for EAE
      susceptibility. IL-23 induces a population of IL-17-producing cells that is more
      critically involved in EAE pathogenesis than Th1 cells. Here, we review the role
      of the IL-23 system in the pathophysiology of EAE.

PMID- 16628263
TI  - Inhibition of ALK5 as a new approach to treat liver fibrotic diseases.
AB  - Liver fibrosis is the result of an unbalanced wound healing response to a chronic
      hepatic injury. Transforming growth factor-beta (TGF-beta) plays a major role in
      this process via the activation of hepatic stellate cells. Various approaches
      have been tested in animal models of fibrosis to block the effects of TGF-beta,
      including antibodies and soluble receptors. Here, we discuss the potential use of
      TGF-beta signaling inhibitors, acting at the TGF-beta type I receptor kinase
      (ALK5) level, as a possible therapy for liver fibrosis. Thus far, there is only
      one ALK5 inhibitor (GW6604) for which activity in models of liver fibrosis has
      been described, showing clear antifibrotic effects resulting in liver function
      improvement. However, due to the pleiotropic effects of TGF-beta, the beneficial
      antifibrotic effects of ALK5 inhibition should be carefully balanced against the
      potential risk of unwanted effects stemming from chronic treatment.

PMID- 16628264
TI  - Retinoic acid receptor-related orphan receptor alpha as a therapeutic target in
      the treatment of dyslipidemia and atherosclerosis.
AB  - Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of
      the nuclear receptor family. Recently, cholesterol (derivatives) has been
      identified as an RORalpha ligand and deorphanized this receptor. RORalpha is
      expressed in many tissues and is therefore a regulator of multiple biological
      processes. Studies of staggerer mice and in vitro assays indicate a beneficial
      modulatory role of RORalpha in the pathogenesis of dyslipidemia, inflammation and
      atherosclerosis. This paper provides an overview on the role of RORalpha in lipid
      metabolism and discusses its potential therapeutic option for treating lipid and
      inflammatory disorders leading to atherosclerosis.

PMID- 16628265
TI  - The controversial role of adenoviral-derived vectors in gene therapy programs:
      where do we stand?
AB  - The high immunogenicity of recombinant adenoviral vectors is one of the major
      issues in the field of gene therapy. Adenoviral-based vectors are susceptible
      both to cytotoxic T-lymphocyte and humoral immune responses. In addition, leaky
      adenoviral genes also render transduced cells susceptible to host immune
      responses. These are the main reasons why adenoviral-based vectors are not
      suitable to correct genetic disorders, which require long-term expression of the
      transgene. Another limit to long-term transgene expression is posed by the fact
      that adenoviral-based vectors do not integrate their genome into the cellular
      chromosomal DNA of transduced cell populations. As it stands, adenoviral-mediated
      gene transfer is a promising tool for cancer therapy and for genetic immunization
      programs against infectious diseases, provided that host immune responses are
      carefully controlled.

PMID- 16628266
TI  - Molecule of the month. Sorafenib.

PMID- 16628267
TI  - A year of advancement and reflection in nephrology science.
AB  - The 38th Annual Meeting of the American Society of Nephrology was held November 8
      13, 2005, in Philadelphia, Pennsylvania, USA. The meeting offered the latest
      findings in basic and clinical nephrology science and was attended by more than
      12,000 specialists from around the world. This year's sessions included 58 basic
      and clinical science symposia, 29 clinical nephrology conference sessions, 24
      official symposia, 51 free communications and three poster sessions. Highlights
      of the meeting are discussed.

PMID- 16628268
TI  - [Tracking, diagnosis and revascularization of coronary arterial disease in type 2
      diabetes: supreme challenges to contemporary medicine, also in Brazil!].

PMID- 16628269
TI  - [Postprandial glycemia].

PMID- 16628270
TI  - [Genetic screening of multiple endocrine neoplasia type 2: experience of the USP
      Endocrine Genetics Unit].
AB  - Multiple endocrine neoplasia type 2 (MEN-2) is an inherited tumor syndrome that
      includes medullary thyroid carcinoma (MTC), primary hyperparathyroidism,
      pheochromocytoma and other non-endocrine diseases. Since the first RET missense
      mutations in association with MEN-2 were identified, RET mutation analysis had a
      great impact in the clinical management of MEN-2, such as in early diagnosis and
      treatment of MTC. Presently, early total thyroidectomy provides real cure of MTC
      for cases in which molecular diagnosis has been performed at early ages. After
      RET mutation identification, family members should be screened for this mutation
      by using methods as DGGE, SSCP, restriction enzyme, genetic sequencing or mini
      sequencing. In this paper, we briefly review our experience with the direct RET
      gene sequencing and DGGE approaches. In 50 typical MEN-2 patients analyzed using
      both methods, we found no false results suggesting that DGGE is a reliable
      screening method for RET proto-oncogene mutation analysis.

PMID- 16628271
TI  - From growth hormone-releasing peptides to ghrelin: discovery of new modulators of
      GH secretion.
AB  - Growth hormone (GH)-releasing hormone and somatostatin modulate GH secretion. A
      third mechanism has been discovered in the last decade, involving the action of
      GH secretagogues. Ghrelin is a new acylated peptide produced mainly by the
      stomach, but also synthesized in the hypothalamus. This compound increases both
      GH release and food intake. The relative roles of hypothalamic and circulating
      ghrelin on GH secretion are still unknown. Endogenous ghrelin might amplify the
      basic pattern of GH secretion, optimizing somatotroph responsiveness to GH
      releasing hormone. This peptide activates multiple interdependent intracellular
      pathways at the somatotroph, involving protein kinase C, protein kinase A and
      extracellular calcium systems. However, as ghrelin induces a greater release of
      GH in vivo, its main site of action is the hypothalamus. In this paper we review
      the available data on the discovery of ghrelin, the mechanisms of action and
      possible physiological roles of GH secretagogues and ghrelin on GH secretion,
      and, finally, the regulation of GH release in man after intravenous
      administration of these peptides.

PMID- 16628272
TI  - [Vitamin D deficiency in adults: to better understand a new presentation of an
      old disease].
AB  - Vitamin D is synthesized in skin through a reaction mediated by sunlight, and it
      is metabolized to 25-hydroxyvitamin D, in liver, and in 1,25-dihydroxyvitamin D,
      in kidney. This last reaction has a tight feedback mechanism. 1,25
      dihydroxyvitamin D is the active hormone, and its actions are mediated mainly by
      nuclear receptors. Its major functions are in calcium metabolism and bone mass
      maintenance. Hypovitaminosis D, as a disease in adult people, manifests itself
      with hypocalcemia and secondary hyperparathyroidism with subsequent loss of
      trabecular bone, thinning of cortical bone, and, eventually, a higher risk of
      fractures. Hypovitaminosis D is a very common condition in Europe, Africa, North
      America and some South American countries, such as Chile and Argentina.
      Measurement of serum total 25-hydroxyvitamin D concentration is the gold standard
      to diagnose vitamin D deficiency. Serum concentrations below 50 nmol/L are
      associated with an increase in parathyroid hormone concentration, and bone loss.
      Risk factors for vitamin D deficiency, like poor sunlight exposition, aging skin
      and factors that interfere with normal vitamin D metabolism, are well
      established. Oral vitamin D supplementation, an easy and inexpensive treatment,
      is needed to treat this illness.

PMID- 16628273
TI  - [Diabetes and coronary stent implantation: experience from a reference center in
      interventional cardiology].
AB  - We evaluated the influence of diabetes mellitus (DM) on clinical outcomes in
      patients with coronary artery disease treated with stent implantation. Between
      1996 and 2000, 934 stents were implanted in 893 patients in our institution; 23%
      of them had DM. Clinical and angiographic characteristics and clinical outcomes
      of the patients with and without DM were prospectively included in a computerized
      database. Diabetics were older (61.5 +/- 10 vs. 59.8 +/- 11 years; p = 0.04) and
      had a higher prevalence of hypertension (69% vs. 62%; p = 0.09). The procedural
      clinical success rate (successful coronary stenting with residual stenosis < 30%,
      TIMI 3 flow and no in-hospital adverse clinical event) was lower in the diabetic
      group (88% vs. 92%; p = 0.05). In the 1-year follow up, diabetic patients showed
      higher rates of new target vessel revascularization (12.3% vs. 8%; p = 0.06),
      death (5.4% vs. 2.5%; p = 0.03) and major adverse cardiovascular events (MACE,
      new angioplasty, surgery, acute myocardial infarction or death: 16.3% vs. 9.3%; p
      = 0.003). Diabetes was independently associated to 1-year MACE on multivariate
      analysis (OR: 2.00; IC: 1.25-3.24; = 0.004). We concluded that DM is associated
      with higher complication and restenosis rates and a higher risk of long-term
      major cardiovascular events in patients treated with coronary stent implantation.

PMID- 16628274
TI  - Value of diagnostic tools for myocardial ischemia used in routine clinical
      practice to predict cardiac events in patients with type 2 diabetes mellitus: a
      prospective study.
AB  - OBJECTIVE: To analyze tests used in routine clinical practice for the diagnosis
      of myocardial ischemia to predict the development of cardiac events in type 2
      diabetic patients. METHODS: The occurrence of cardiac events (new myocardial
      infarct, myocardial re-vascularization procedures, congestive heart failure,
      acute pulmonary edema, sudden death, and death after myocardial infarction or
      pulmonary edema) were prospectively assessed in a cohort of 135 type 2 diabetic
      patients after up to seven years of follow-up. At baseline, coronary artery
      disease was assessed by the WHO cardiovascular questionnaire, resting
      electrocardiogram, and stress myocardial scintigraphy. RESULTS: Forty-eight
      cardiac events were observed in 41 patients (10.5 events/100 patients-year). In a
      Cox's proportional-hazard model only the presence of symptoms of coronary artery
      disease on the WHO cardiovascular questionnaire alone (RR = 2.13, 95% CI 1.11
      4.07, P= 0.022) or in combination with abnormalities on resting ECG (RR= 2.03,
      95% CI 1.05-3.92, P= 0.034) or on myocardial scintigraphy (RR= 1.89, 95% CI 1.001
      3.57, P= 0.050) predicted cardiac events, adjusted for fasting plasma glucose,
      mean blood pressure, body mass index, peripheral vascular disease and diabetic
      nephropathy. CONCLUSION: The WHO cardiovascular questionnaire, a simple tool for
      the diagnosis of coronary artery disease, is a significant predictor of cardiac
      events in type 2 diabetic patients.

PMID- 16628275
TI  - [Contribution of post-breakfast plasma glucose to the glycemic control of type 2
      diabetic patients].
AB  - Epidemiological studies have documented that postprandial hyperglycemia is the
      main risk factor for cardiovascular diseases. It has been established that
      glycated hemoglobin (HbA1C) provides an integrated measure of plasma glucose (PG)
      of the last 2-3 months. However, the relative contribution of fasting PG (FPG)
      and postprandial PG (PPG) to the HbA1C value is controversial. OBJECTIVE: To
      evaluate FPG and PPG contributions to the HbA1C value in patients with type 2
      diabetes mellitus (DM2). METHODS: 53 subjects with stable DM2 were studied. They
      were treated with oral anti-diabetic agents (n = 27) and/or insulin (n = 26).
      Each subject went to 3 visits at 2-month-intervals. On each visit, FPG, PPG (2 h
      after breakfast and lunch), and HbA1C were measured and we provided breakfast and
      lunch according to their meal habits. PG was measured by glucose-oxidase and
      HbA1C by ion-exchange chromatography. Statistical analysis was performed by
      correlation coefficients at a < 0.05 P value. RESULTS: Correlations were stronger
      between HbA1C and post-breakfast PG (r: 0.66-0.48), mean FPG (r: 0.64-0.41),
      glucose area under the curve (r: 0.64-0.46), and mean PPG (r: 0.59-0.41).
      CONCLUSIONS: Measurement of post-breakfast PG showed to be another valuable tool
      for type 2 diabetic glucose control monitoring.

PMID- 16628276
TI  - [Prevalence of overweight and obesity in school children of Santos city, Brazil].
AB  - The aim of this population-based study was to estimate the prevalence of
      overweight and obesity in public and private schools of Santos city, Brazil. We
      evaluated a total of 10,822 children aged 7 to 10 years old. Determination of
      overweight and obesity was obtained by the 85th and 95th percentiles of BMI for
      age, respectively, as proposed by CDC in 2000. The overall prevalence rates of
      overweight and obesity were 15.7% (CI 95%= 15.0% to 16.4%) and 18.0% (17.3% to
      18.7%), respectively. The prevalence of overweight was 13.7% (12.6% a 14.8%) in
      boys and 14.8% (13.7% a 15.9%) in girls of public schools. In private schools,
      the rates were 17.7% (15.7% to 19.7%) in boys and 22.2% (20.0% to 24.4%) in
      girls. Obesity was found in 16.9% (15.7% to 18.1%) of the boys and 14.3% (13.2%
      to 15.4%) of the girls of public schools. In the private schools, 29.8% (27.4% to
      32.2%) of the boys and 20.3% (18.2% to 22.4%) of the girls were obese. We
      concluded that the prevalence of obesity in public and private schools in the
      city of Santos is higher than other studies conducted in Brazil and in other
      countries of Latin America. Private schools showed higher prevalence rates of
      obesity than public schools (p= 0.001).

PMID- 16628277
TI  - [Effects of growth hormone on anthropometric and metabolic parameters in android
      obesity].
AB  - The aim of the study was to evaluate the effect of GH on body weight, body
      composition and cardiovascular risk factors in android obese men. Forty non
      diabetic subjects aged 20 to 50 years-old with android obesity (WHR > 1) were
      divided in two groups, on a prospective randomized double-blind basis to receive
      treatment with GH (0.050 U/kg/day) or placebo for three months. Bioimpedance
      analysis, DEXA, indirect calorimetry and cardiovascular risk factors were done at
      the beginning and at the end of the study. Anthropometric measurements were
      evaluated monthly. Body weight was reduced (3.5 +/- 2.9 kg), as well as BMI (1.2
      +/- 1.0 kg/m2), WHR (0.04 +/- 0.01) and fat mass (2.4 +/- 1.0 kg), total
      cholesterol (4.0 +/- 3.3 mg/dL) and LDL-cholesterol (5.7 +/- 2.7 mg/dL) in GH
      treated patients. Percentual changes were statistically different from placebo.
      Benefits and risks of long-term GH use in obese patients are still largely
      unknown.

PMID- 16628278
TI  - [Obstructive sleep apnea and hypopnea syndrome (OSAHS): association with obesity,
      gender and age].
AB  - Obstructive sleep apnea and hypopnea syndrome (OSAHS) has been the focus of
      extensive research because of its association with neurocognitive and
      cardiovascular complications. The aim of this study was to evaluate the frequency
      and association between OSAHS and the class of obesity, gender and age in
      outpatients referred to a sleep laboratory. We selected 1,595 patients, 71.7%
      male. Mean +/- SD age was 46.7 +/- 11.7 years, BMI was 28.1 +/- 5.1 kg/m2 and AIH
      was 13.9 +/- 15.5 events/ hour of sleep. The patients were considered apneic when
      the apnea-hypopnea index (AHI) was > 5 events/hour of sleep; OSAHS was present
      in: (1) 71.1% of men and 50.3% of women (p < 0.001); (2) in 45.3% of patients
      with normal BMI, in 64.3% of those overweighed and in 80% of obese (p < 0.001).
      According to age, 61.2% with age < 55 were apneic, as well as 78% of those with
      age > 55 years old (p < 0.001). We concluded that OSAHS was directly and strongly
      associated to the male gender, obesity class and to aging.

PMID- 16628279
TI  - [Cardiac morphology and performance alterations and analysis of determinant
      factors of left ventricular hypertrophy in 40 patients with acromegaly].
AB  - Acromegaly has a high mortality rate due mainly to cardiovascular complications.
      The aim was to evaluate the determinant factors of left ventricular hypertrophy
      (LVH) and cardiac alterations in 40 acromegalic patients submitted to clinical
      laboratorial studies and echocardiogram. The variables analyzed were age, sex,
      disease duration, arterial hypertension (AH), impaired glucose tolerance/DM,
      previous treatment with octreotide, GH and %IGF-I. Univaried analysis showed that
      patients with LVH were older (p= 0.031), had higher prevalence of AH (p= 0.009)
      and higher %IGF-I (p= 0.002), than those without LVH. Multivaried analysis showed
      AH and %IGF-I as determinants of LVH (p= 0.035 and p= 0.016). After dichotomizing
      of %IGF-I, a score was created and the frequency of LVH was 9%, 65%, 92% x 0, 1,
      2; p< 0.0001. Prevalence of aortic ectasia was higher and valvar disease was
      smaller than reported in the literature. We conclude that AH and %IGF-I were
      determinants of LVH.

PMID- 16628280
TI  - Managing thyroid cancer without thyroxine withdrawal.
AB  - Thyroxine (T4) withdrawal or recombinant TSH is used for the stimulation of
      thyroglobulin (Tg), whole-body scanning (WBS) and iodine-131 treatment in
      patients with thyroid carcinoma. This study evaluated the T4 dose reduction
      protocol as an alternative for patients' preparation. Fifty-one patients were
      submitted to total T4 withdrawal for WBS and Tg measurement. T4 treatment was
      then resumed and maintained until TSH reached levels < 0.3 mIU/l. The T4 dose was
      then decreased to 0.8 microg/kg/day and TSH was measured weekly. Tg was assayed
      when TSH was > 30 mIU/l. Patients diagnosed with the disease upon initial
      evaluation were treated. We also evaluated the clinical and laboratory changes
      observed for both preparations. Using the reduced dose protocol, TSH levels > 30
      mIU/l were reached within 6 and 8 weeks in 84.6 and 100% of the patients,
      respectively. T4 withdrawal was associated with more common symptoms of
      hypothyroidism and elevation of creatine kinase (CK) and LDL cholesterol. The T4
      dose reduction protocol proved to be useful for Tg stimulation and ablative
      therapy, without the complication of severe hypothyroidism or the cost of
      recombinant TSH.

PMID- 16628281
TI  - [Percutaneous ethanol injection for the treatment of thyroid nodules].
AB  - To verify the effectiveness of percutaneous ethanol injection (PEI) in the
      treatment of thyroid nodules (TN), we analyzed 86 TN from 77 patients before and
      after one or two sessions of PEI. The medians of the initial and final volumes
      were: 3.5 mL (range 0.3-82.7) and 1.8 mL (range 0-29.4). Seven percent of the
      nodules disappeared and the mean nodule size reduction was 52.6% (p< 0.0001).
      After ethanol injection, the median volume reduction was: 37.3% (range -39.0
      82.6) for solid; 53.5% (14.6-88.0) for mostly solid; 58.0% (21.0-64.5) for mixed;
      71.0% (18.8-100.0) for mostly cystic and 90.0% (45.9-100.0) for cystic lesions.
      Furthermore, we compared the variation of the greatest diameter of TN, without
      any treatment and after PEI, and found this difference statistically significant
      (p< 0.00001). Pain was the most common complication, although this was mostly
      described as moderate (27.6%). We conclude that PEI is an efficient and safe
      treatment option for benign TN.

PMID- 16628282
TI  - [A predictive analysis from bone mineral density among eutrophic Brazilian male
      adolescents].
AB  - Osteoporosis is considered one of the most serious public health diseases and
      studies show that it is a pediatric disease that manifests during senility. It is
      usually diagnosed in clinical practice by dual-energy x-ray absorptiometry (DXA).
      This exam has a high cost and it is difficult to apply to a pediatric population
      because specific equipment and special software are required. This study presents
      predictive equations to evaluate the bone mineral density (BMD) among male
      adolescents. To better predict the equations, some parameters were used as the
      bone age (by left hand and wrist x-ray), pubertal stages, weight, height and the
      lumbar spine and femur BMD from 61 healthy adolescents, ages 10 through 19 years.
      The prediction models were carried through analysis of multiple regressions
      stepwise. The results have indicated a prediction model for BMD with a
      coefficient of 0.87 and 0.80, respectively for the spine and the femoral regions.
      In conclusion, the results have confirmed that BMD depends on the skeletal age
      and the physical growth during adolescence. The proposed equations are easy to
      use, has a low operational cost, and the clarification rate is 75% and 65% for
      lumbar spine and femoral BMD, respectively.

PMID- 16628283
TI  - Relation between insulin resistance and hematological parameters in a Brazilian
      sample.
AB  - It has already been demonstrated that insulin resistance (IR) is associated with
      the stimulation of erythroid progenitors and with increased levels of
      inflammation markers. Therefore, IR should also be associated with increased red
      blood cell (RBC) and white blood cell (WBC) count. The aim of this study is to
      demonstrate that IR is independently associated with altered hematological
      parameters in a Brazilian sample. We analyzed laboratorial exams from 925
      subjects. All data on hematological parameters, insulin resistance (Homeostasis
      Model Assessment [HOMA]) and lipid levels were included in the analysis.
      Demographic information included age and gender. HOMA correlated positively with
      RBC (r= 0.17, p< 0.001), plasma hemoglobin concentrations (r= 0.14, p< 0.001),
      hematocrit value (r= 0.15, p< 0.001) and WBC (r= 0.17, p< 0.01). Subjects in the
      upper quartile of IR had higher levels of plasma glucose, fasting insulin,
      triglycerides, hematocrit, hemoglobin, RBC and WBC count than those in the lower
      quartile. In conclusion, IR seems to be associated with alterations in several
      hematological parameters. These hematological alterations may be considered an
      indirect feature of the IR syndrome.

PMID- 16628284
TI  - [Evaluation of hypothalamic-pituitary-adrenal axis recovery after corticotherapy
      by using basal cortisol secretion].
AB  - The glucocorticoid-induced inhibition that occurs after discontinuation of
      treatment is the most frequent cause of adrenal insufficiency. There are yet some
      doubts about the best way of evaluating the hypothalamic-pituitary-adrenal (HPA)
      axis in those patients. The main objective of this study was to evaluate the
      utility of basal cortisol in diagnosing adrenal insufficiency. Thirty-five
      children with acute lymphoid leukemia (ALL) receiving glucocorticoid therapy
      (median age of 6.9 years) were evaluated. A stimulus test with corticotropin
      releasing hormone (CRH-1 mcg/kg) was performed before the introduction of
      dexamethasone (6 mg/m2/day, for 28 days), in the 8th and the 28th days of
      glucocorticoid therapy, and 48 hours and one month after discontinuation of
      therapy. Suppression of the basal secretion as well as the maximum concentration
      of cortisol (post-CRH) occurred during glucocorticoid therapy, which persisted
      for 48 hours after the steroid was removed from treatment (p< 0.01 and p< 0.0001,
      respectively, for the three tests). One month after ceasing the administration of
      the glucocorticoid, the basal secretion, as well as the maximum concentration of
      cortisol, were similar to that before glucocorticoid therapy. There was a
      positive and statistically significant correlation between basal secretion and
      maximum concentration of cortisol in all tests. We observed 95% of specificity
      for the diagnosis of adrenal insufficiency when the inferior limit of basal
      cortisol was 8.5 mcg/dl. According to these results we concluded that basal
      secretion of cortisol is a good marker of supra-renal function in evaluating
      children after discontinuation of glucocorticoid therapy.

PMID- 16628285
TI  - [Brazilian Diabetes Society consensus statement--intensive insulin therapy and
      insulin pump therapy].
AB  - This article reports the Brazilian Diabetes Society consensus statement on
      intensive insulin therapy and insulin pump therapy, arrived at during an update
      symposium held in 2003 for this specific purpose. The concepts underlying these
      modalities of diabetes treatment are outlined, their fundaments are given, and
      practical issues about their indications, feasibility, limits, techniques and
      cost-benefit relationships are analyzed. The techniques comprise the suggested
      self-monitoring schedules and the insulin doses, types, forms of administration
      and correction factors used in each modality of intensive treatment, for both
      type 1 and 2 diabetes. The roles of SBD in the implementation of these treatments
      and of the different professionals involved are discussed and commented. The
      conclusions are based on consensual answers to some orienting questions
      formulated during the symposium's presentation.

PMID- 16628286
TI  - [Nationwide multicenter study on the prevalence of overweight and obesity in type
      2 diabetes mellitus in the Brazilian population].
AB  - AIM: To evaluate the prevalence of overweight and obesity in type 2 diabetic
      (DM2) outpatients from different regions of Brazil. PATIENTS AND METHODS: We
      studied 2,519 randomly selected patients, from 11 hospitals, 2 endocrine and one
      general public care clinics from 10 cities. Overweight was defined as body-mass
      index (BMI) > 25 and obesity as BMI > 30 kg/m2. Glycemic control (GC) was
      evaluated by GC index (GCI = patient's HbA1 or HbA1c/upper limit of normal for
      the method x 100). RESULTS: 39% of the population studied was male, the mean age
      was 58.8 +/- 11.6 y, the duration from clinical diagnosis of DM2 was 9.0 +/-
      7.3y, and BMI was 28.3 +/- 5.2 kg/m2. No measurements of BMI were recorded from
      265 patients (10.5%). Patients from the Northeast presented lower BMI as compared
      with those from the Midwest, Southeast and South areas, respectively (26.4 +/-
      4.7 vs. 27.9 +/- 4.8 vs. 29.2 +/- 5.1 vs. 29.4 +/- 5.4 kg/m2; p < 0.001). A
      greater prevalence of obesity was observed in the Southeast and South areas as
      compared to the Northeast (p < 0.001), as well as in the female group,
      respectively (69% vs. 31%; p < 0.001). Normal weight patients presented lower
      GCI. Patients being treated with two or more oral drugs and an association of
      insulin plus oral drug presented greater BMI values than those being treated with
      diet, oral hypoglycemic agents and insulin p < 0.001. The BMI of patients treated
      by a specialist did not differ from those treated by a generalist. CONCLUSIONS:
      75% of our sample was out of adequate BMI and 30% was obese. The percentage of
      patients with overweight and obesity was comparable to those found in similar
      European studies but still lower than those found in the USA. The prevalence of
      obesity in diabetic patients was three times higher than in the overall Brazilian
      population according to data from the Brazilian Institute of Geography and
      Statistics (IBGE).

PMID- 16628287
TI  - [Slight hormonal alterations in a patient with a large pheochromocytoma].
AB  - We present a case report that the patient had symptoms suggesting
      pheochromocytoma, a large tumor (> 50 g) and a single minimally altered
      laboratorial test, exemplifying a diagnostic pitfall. A 31 y.o. male patient had
      two acute abdominal events, the last one accompanied by headache, arterial
      hypertension, facial flushing, perspiration and cutaneous pallor. In another
      admission, the patient had sustained arterial hypertension and cardiac
      arrhythmia. From laboratory analysis, the vanililmandelic acid was slightly
      modified. Scintigraphy disclosed a large adrenal mass suggesting
      pheochromocytoma. Histopathology confirmed this hypothesis. This report points
      out that patients with symptoms suggesting pheochromocytoma, even when plasma
      catecholamines and urinary metanephrines levels are normal, may harbor large
      tumors with a high catecholamines turnover or that had undergone hemorrhagic
      necrosis.

PMID- 16628288
TI  - [Hyperparathyroidism associated with hypophosphatemic osteomalacia: case report
      and review of the literature].
AB  - Adult-onset hypophosphatemic osteomalacia is a rare disease characterized by
      hypophosphatemia, increased levels of alkaline phosphatase and decreased bone
      mass. Oral supplementation with phosphate and vitamin D is the main treatment
      and, in cases of oncogenic osteomalacia, tumor resection is mandatory. We report
      the case of a patient with hypophosphatemic osteomalacia of an unknown cause.
      Despite extensive search, no tumor was found. The patient was treated with
      phosphate for a long period and developed tertiary hyperparathyroidism. Serum PTH
      levels did not return to normal after surgical excision of three parathyroids and
      the patient refused to continue clinical investigation and treatment. After ten
      years absent from the hospital, during which medications were used irregularly,
      she was admitted with multiple fractures and respiratory insufficiency caused by
      severe thoracic deformities, and died. The authors discuss the relationship
      between osteomalacia and hyperparathyroidism and the aggressive course of the
      disease.

PMID- 16628289
TI  - [Hormonal therapy of the menopause based on evidences].

PMID- 16628291
TI  - Improving the quality of emergency care for children in developing countries.

PMID- 16628292
TI  - How quality improvement in health care can help to achieve the Millennium
      Development Goals.

PMID- 16628293
TI  - Suicide, suicide attempts and pesticides: a major hidden public health problem.

PMID- 16628294
TI  - China's pragmatic approach to AIDS.

PMID- 16628295
TI  - New fund-raising scheme fuses profit with philanthropy.

PMID- 16628296
TI  - Tough measures in Russian prisons slow spread of TB.

PMID- 16628297
TI  - Tackling social factors to improve health.

PMID- 16628299
TI  - Failure of standard antimicrobial therapy in children aged 3-59 months with mild
      or asymptomatic HIV infection and severe pneumonia.
AB  - OBJECTIVE: To determine whether children aged 3-59 months with mild or non
      symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe
      pneumonia have a higher failure rate than do HIV-uninfected children when treated
      with the standard WHO treatment of parenteral penicillin or oral amoxicillin.
      METHODS: This study was a planned sub-analysis of a randomized trial of 3-59
      month-old children presenting with WHO-defined severe pneumonia (the APPIS
      study). We included two sites with high HIV prevalence in Durban, South Africa
      and Ndola, Zambia. Primary outcome measures were clinical treatment failure at
      day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER:
      CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523
      children enrolled, HIV status was known for 464 participants; 106 (23%) of these
      were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and
      110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day
      2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07;
      95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected
      children failed treatment by day 14 compared with 76 (21.2%) uninfected children
      (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the
      greatest differential in treatment failure at day 2 and day 14 occurred in the
      children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe
      pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin
      at day 2 and day 14 more often than do HIV-uninfected children, especially young
      infants. Standard case management of acute respiratory infection (ARI) using WHO
      treatment guidelines is inadequate in areas of high HIV prevalence and
      reappraisal of empiric antimicrobial therapy is urgently needed for severe
      pneumonia associated with HIV-1.

PMID- 16628300
TI  - Patterns of hospital transfer for self-poisoned patients in rural Sri Lanka:
      implications for estimating the incidence of self-poisoning in the developing
      world.
AB  - OBJECTIVES: Most data on self-poisoning in rural Asia have come from secondary
      hospitals. We aimed to: assess how transfers from primary to secondary hospitals
      affected estimates of case-fatality ratio (CFR); determine whether there was
      referral bias according to gender or poison; and estimate the annual incidence of
      all self-poisoning, and of fatal self-poisoning, in a rural developing-world
      setting. METHODS: Self-poisoning patients admitted to Anuradhapura General
      Hospital, Sri Lanka, were reviewed on admission from 1 July to 31 December 2002.
      We audited medical notes of self-poisoning patients admitted to 17 of the 34
      surrounding peripheral hospitals for the same period. FINDINGS: A total of 742
      patients were admitted with self-poisoning to the secondary hospital; 81 died
      (CFR 10.9%). 483 patients were admitted to 17 surrounding peripheral hospitals.
      Six patients (1.2%) died in peripheral hospitals, 249 were discharged home, and
      228 were transferred to the secondary hospital. There was no effect of gender or
      age on likelihood of transfer; however, patients who had ingested oleander or
      paraquat were more likely to be transferred than were patients who had taken
      organophosphorus pesticides or other poisons. Estimated annual incidences of self
      poisoning and fatal self-poisoning were 363 and 27 per 100,000 population,
      respectively, with an overall CFR of 7.4% (95% confidence interval 6.0-9.0).
      CONCLUSION: Fifty per cent of patients admitted to peripheral hospitals were
      discharged home, showing that CFRs based on secondary hospital data are inflated.
      However, while incidence of self-poisoning is similar to that in England, fatal
      self-poisoning is three times more common in Sri Lanka than fatal self-harm by
      all methods in England. Population based data are essential for making
      international comparisons of case fatality and incidence, and for assessing
      public health interventions.

PMID- 16628301
TI  - Maternal mortality in St. Petersburg, Russian Federation.
AB  - OBJECTIVE: To study the levels and causes of maternal mortality in St.
      Petersburg, Russian Federation. METHODS: We collected data about all pregnancy
      related deaths in St. Petersburg over the period 1992-2003 using several sources
      of information. An independent research group reviewed and classified all cases
      according to ICD-10 and the Confidential Enquiries into Maternal Deaths in the
      United Kingdom. We tested trends of overall and cause specific ratios (deaths per
      100,000 births) for four 3-year intervals using the chi2 test. FINDINGS: The
      maternal mortality ratio for the study period was 43 per 100,000 live births. A
      sharp decline of direct obstetric deaths was observed from the first to fourth 3
      year interval (49.8 for 1992-94 versus 18.5 for 2001-03). Sepsis and haemorrhage
      were the main causes of direct obstetric deaths. Among the total deaths from
      sepsis, 63.8% were due to abortion. Death ratios from sepsis declined
      significantly from the first to second study interval. In the last study interval
      (2001-03), 50% of deaths due to haemorrhage were secondary to ectopic
      pregnancies. The death ratio from thromboembolism remained low (2.9%) and stable
      throughout the study period. Among indirect obstetric deaths a non-significant
      decrease was observed for deaths from cardiac disease. Death ratios from
      infectious causes and suicides increased over the study period. CONCLUSIONS:
      Maternal mortality levels in St. Petersburg still exceed European levels by a
      factor of five. Improved management of abortion, emergency care for sepsis and
      haemorrhage, and better identification and control of infectious diseases in
      pregnancy, are needed.

PMID- 16628302
TI  - A comparison of cluster and systematic sampling methods for measuring crude
      mortality.
AB  - OBJECTIVE: To compare the results of two different survey sampling techniques
      (cluster and systematic) used to measure retrospective mortality on the same
      population at about the same time. METHODS: Immediately following a cluster
      survey to assess mortality retrospectively in a town in North Darfur, Sudan in
      2005, we conducted a systematic survey on the same population and again measured
      mortality retrospectively. This was only possible because the geographical layout
      of the town, and the availability of a good previous estimate of the population
      size and distribution, were conducive to the systematic survey design. RESULTS:
      Both the cluster and the systematic survey methods gave similar results below the
      emergency threshold for crude mortality (0.80 versus 0.77 per 10,000/day,
      respectively). The results for mortality in children under 5 years old (U5MR)
      were different (1.16 versus 0.71 per 10,000/day), although this difference was
      not statistically significant. The 95% confidence intervals were wider in each
      case for the cluster survey, especially for the U5MR (0.15-2.18 for the cluster
      versus 0.09-1.33 for the systematic survey). CONCLUSION: Both methods gave
      similar age and sex distributions. The systematic survey, however, allowed for an
      estimate of the town's population size, and a smaller sample could have been
      used. This study was conducted in a purely operational, rather than a research
      context. A research study into alternative methods for measuring retrospective
      mortality in areas with mortality significantly above the emergency threshold is
      needed, and is planned for 2006.

PMID- 16628303
TI  - A method for deriving leading causes of death.
AB  - OBJECTIVE: A standard list for ranking leading causes of death worldwide does not
      exist. WHO headquarters, regional offices and Member States all use different
      lists that have varying levels of detail. We sought to derive a standard list to
      enable countries to identify their leading causes of death and to permit
      comparison between countries. Our aim is to share the criteria and methodology we
      used to bring some order to the construction of such a list, to provide a
      consistent procedure that can be used by others, and to give researchers and data
      owners an opportunity to utilize the list at national and subnational levels.
      METHODS: Results were primarily data-driven. Data from individual countries
      representing different regions of the world were extracted from the WHO Mortality
      Database. Supplementary information from WHO estimates on mortality was used for
      regions where data were scarce. In addition, a set of criteria was used to group
      the candidate causes and to determine other causes that should be included on the
      list. FINDINGS: A ranking list of the leading causes of death that contains broad
      cause groupings (such as "all cancers", "all heart diseases" or "all accidents")
      is not effective and does not identify the leading individual causes within these
      broad groupings; thus it does not allow policy-makers to generate appropriate
      health advocacy and cost-effective interventions. Similarly, defining candidate
      causal groups too narrowly or including diseases that have a low frequency does
      not meet these objectives. CONCLUSION: For international comparisons, we
      recommend that countries use this list; it is based on extensive evidence and the
      application of public health disease-prevention criteria. It is not driven by
      political or financial motives. This list may be adapted for national statistical
      purposes.

PMID- 16628304
TI  - Preventable risk factors for noncommunicable diseases in rural Indonesia:
      prevalence study using WHO STEPS approach.
AB  - OBJECTIVE: To gain a better understanding of the health transition in Indonesia,
      we sought to describe the prevalence and distribution of risk factors for
      noncommunicable diseases and to identify the risk-factor burden among a rural
      population and an urban population. METHODS: Using the protocol of the WHO
      STEPwise approach to Surveillance (STEPS), risk factors for noncommunicable
      diseases were determined for 1502 men and 1461 women aged 15-74 years at the
      Purworejo Demographic Surveillance Site in 2001. FINDINGS: Smoking prevalence was
      high among men (913/1539; weighted percentage=53.9.%) in both rural and urban
      populations; it was almost non-existent among women. A higher proportion of the
      urban population and the richest quintile of the rural population had high blood
      pressure and were classified as being overweight or obese when compared with the
      poorest quintile of the rural population. Those classified as being in the
      richest quintile who lived in the rural area were 1.5 times more likely to have
      raised blood pressure and 8 times more likely to be overweight than those
      classified as being in the poorest quintile and living in the rural area.
      Clustering of risk factors was higher among those classified as being in the
      richest quintile of those living in the rural area compared with those classified
      as being in the poorest quintile; and the risks of clustering were just 20-30%
      lower compared with the urban population. CONCLUSION: Both the rural and urban
      populations in Purworejo face an unequally distributed burden of risk factors for
      noncommunicable diseases. The burden among the most well-off group in the rural
      area has already reached a level similar to that found in the urban area. The
      implementation of the WHO STEPS approach was feasible, and it provides a
      comprehensive picture of the burden of risk factors, allowing appropriate health
      interventions to be implemented to address health inequities.

PMID- 16628305
TI  - Improved triage and emergency care for children reduces inpatient mortality in a
      resource-constrained setting.
AB  - PROBLEM: Early assessment, prioritization for treatment and management of sick
      children attending a health service are critical to achieving good outcomes. Many
      hospitals in developing countries see large numbers of patients and have few
      staff, so patients often have to wait before being assessed and treated.
      APPROACH: We present the example of a busy Under-Fives Clinic that provided
      outpatient services, immunizations and treatment for medical emergencies. The
      clinic was providing an inadequate service resulting in some inappropriate
      admissions and a high case-fatality rate. We assessed the deficiencies and sought
      resources to improve services. LOCAL SETTING: A busy paediatric outpatient clinic
      in a public tertiary care hospital in Blantyre, Malawi. RELEVANT CHANGES: The
      main changes we made were to train staff in emergency care and triage, improve
      patient flow through the department and to develop close cooperation between
      inpatient and outpatient services. Training coincided with a restructuring of the
      physical layout of the department. The changes were put in place when the
      department reopened in January 2001. LESSONS LEARNED: Improvements in the process
      and delivery of care and the ability to prioritize clinical management are
      essential to good practice. Making the changes described above has streamlined
      the delivery of care and led to a reduction in inpatient mortality from 10-18%
      before the changes were made (before 2001) to 6-8% after.

PMID- 16628306
TI  - Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral
      therapy in Malawi.
AB  - OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used
      to assess the delivery of antiretroviral therapy during nationwide scale-up of
      treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the
      Ministry of Health and its partners (the Lighthouse Clinic; Medecins Sans
      Frontieres-Belgium, Thyolo district; and WHO's Country Office) undertook
      structured supervision and monitoring of all public sector health facilities in
      Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that
      by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%)
      adults) who had ever started antiretroviral therapy. Of patients who had ever
      started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8%
      (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1%
      (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to
      another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were
      ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side
      effects; and, based on pill counts, 96% (6824/7114) had taken their treatment
      correctly. Mistakes in the registration and monitoring of patients were
      identified and corrected. Drug stocks were checked, and one potential drug stock
      out was averted. As a result of the supervisory visits, by the end of March 2005
      recruitment of patients to facilities scheduled to start delivering
      antiretroviral therapy had increased. CONCLUSION: This report demonstrates the
      importance of early supervision for sites that are starting to deliver
      antiretroviral therapy, and it shows the value of combining data collection with
      supervision. Making regular supervisory and monitoring visits to delivery sites
      are essential for tracking the national scale-up of delivery of antiretrovirals.

PMID- 16628307
TI  - Translating words into actions: are governments acting on the advice of the World
      health report?
AB  - Every year, WHO produces the World health report: the 2005 report concentrated on
      maternal, neonatal and child health. But what is the value of these reports? Are
      they ritualistic publications designed to promote WHO, or are they worthy of
      proper discussion and debate? One would think that given the current crises in
      global health, the annual report of the UN's primary agency for health would be
      important. However, unless there is evidence that these reports are taken
      seriously, discussed and debated, and shown to have an effect, a conclusion might
      be drawn that they are largely insignificant. And that would consign WHO to a
      level of insignificance that it does not warrant. In this discussion of the 2005
      report, I aim to provoke a response from both WHO and the international health
      community to demonstrate that the annual World health reports are meaningful.
      Furthermore, I suggest here that WHO shows its commitment to the recommendations
      of the 2005 report by monitoring how well recommendations have been taken
      forward.

PMID- 16628310
TI  - Composite index of anthropometric failure (CIAF) classification: is it more
      useful?

PMID- 16628312
TI  - Dual job holding by public-sector health professionals may be beneficial to
      patients.

PMID- 16628313
TI  - Clinical trial registry initiative.

PMID- 16628315
TI  - Fifteen years ago laser was supposed to open arteries, now it is supposed to
      close veins: what is the reality behind the tool?
AB  - Laser first emerged as a technology for use in the vascular arena nearly 20 years
      ago. The ability of laser to evaporate atherosclerotic plaque was extensively
      studied; however, the goal of creation of an adequate channel without arterial
      wall perforation proved to be elusive, and the technique fell into disfavor. More
      than a decade later, interest in lasers was sparked again with its application to
      endovenous thermal ablation of axial superficial venous reflux. The mechanism of
      action of endovenous laser therapy involves thermal damage of the vein wall,
      resulting in destruction of the intima and collagen denaturation of the media
      with eventual fibrotic occlusion of the vein. Apart from the obvious attraction
      of a minimally invasive procedure to ablate superficial venous reflux with its
      attendant benefits, another advantage of laser ablation includes a potentially
      decreased incidence of neovascularization in the groin secondary to preservation
      of superficial venous drainage of the abdominal wall. Early success in terms of
      ablation of the refluxing saphenous vein has been reported as 90% to 95%. Minor
      complications are reported in 3% to 10% of patients and include bruising around
      the puncture site, transient paresthesias, superficial phlebitis, and skin burns
      or pigmentation. The more serious complications of deep venous thrombosis or
      extension of thrombus into the femoral vein have been variously reported in 0% to
      2.3% of limbs treated. Pulmonary embolism is extremely rare. There is a learning
      curve, with a decrease in the incidence of all complications with experience. The
      importance of detailed preoperative and intraoperative duplex ultrasound
      examination cannot be overemphasized. The identification of all refluxing venous
      segments and their ablation is the key to optimizing the rate of successful
      ablation to 97% at 1 year and minimizing recurrence of varicose veins. With
      encouraging early and mid-term results with endovenous laser therapy, future
      developments in this field must mandate standardization of technical aspects,
      follow-up imaging, and reporting.

PMID- 16628317
TI  - Commentary on "Fifteen years ago laser was supposed to open arteries, now it is
      supposed to close veins: what is the reality behind the tool".

PMID- 16628318
TI  - Retrievable IVC filters: a decision matrix for appropriate utilization.
AB  - The use of vena caval filters for patients at high risk for or with venous
      thromboembolism has increased substantially during the past two decades. Advances
      in technology have improved the ease of insertion, increasing physicians'
      acceptance of the procedure. Until recently, all vena caval filters available in
      the United States were considered permanent, but since 2003, three nonpermanent
      or retrievable-filters have been approved by the Food and Drug Administration.
      This article reviews the indications for caval filtration in patients at risk for
      venous thromboembolic events. A decision matrix is suggested for use of
      retrievable (optional) vena caval filters.

PMID- 16628319
TI  - Commentary on "Retrievable IVC filters: a decision matrix for appropriate
      utilization".

PMID- 16628321
TI  - Beyond the instructions for use: pushing the limits of infrarenal device
      application for abdominal aortic aneurysms.
AB  - Endograft devices are used to treat 40% to 80% of patients with abdominal aortic
      aneurysms. A much smaller percentage of patients have ideal anatomy, for which
      the devices were designed. Vascular surgeons and interventionalists have become
      increasingly creative in endograft placement to exclude aneurysms, despite the
      presence of complex aortoiliac anatomy. Arterial diameter and angulation are the
      most common barriers to successful endograft placement. In response to this need,
      graft manufacturers are increasing graft size choices, improving device
      flexibility, and providing improved arterial wall fixation. Despite newer
      devices, providers still must push the limits of defined anatomy based on the
      manufacturers recommended instructions to repair most infrarenal aneurysms.

PMID- 16628322
TI  - Commentary on "Beyond the instructions for use: pushing the limits of infrarenal
      device application for abdominal aortic aneurysms".

PMID- 16628324
TI  - Patient selection: lesion characteristics and predictors of outcome.
AB  - Patient selection based on predictors of outcome and lesion characteristics has
      been a strong part of vascular surgeons performing endovascular peripheral
      arterial interventions. The TansAtlantic Inter-Society Consensus (TASC) has
      defined plaque morphology for iliac and femoropopliteal artery lesions. TASC also
      outlines other indicators of success including the indication of claudication,
      proximal lesion location, focal morphology, multivessel run-off, male gender, and
      no diagnosis of diabetes mellitus or renal failure. This information guides the
      vascular surgeon as to what lesions may be best treated by endovascular means.
      Furthermore, outcome of interventions has been linked to types of TASC lesions
      treated. Other factors, not specifically addressed by TASC may play a vital role
      in determining who may be at increased risk of failure and alter patient
      selection for an endovascular intervention. These include calcification load,
      risk of embolism, tortuosity, artery diameter, and proximity to other structures
      such aneurysms, side branches, or graft anastomoses. Refining patient selection
      can also be improved by review of predictors of endovascular complications.
      Herein, information is provided to improve patient selection based on lesion
      characteristics and predictors of outcome.

PMID- 16628326
TI  - Commentary on "Patient selection: lesion characteristics and predictors of
      outcome".

PMID- 16628327
TI  - Crossing chronic total occlusions of the iliac and femoral-popliteal vessels and
      the use of true lumen reentry devices.
AB  - Treatment of chronic total occlusions of the iliac and femoral-popliteal vessels
      with endovascular techniques has become the standard approach for shorter lesions
      and is increasingly applied to long, complex arterial occlusive lesions. As the
      complexity of the arterial occlusions increases, the demands for technical skills
      and devices needed to successfully cross and treat the occlusion also increases.
      We describe here our technique for treatment of iliac and femoral-popliteal
      occlusions. Important aspects of that that have allowed for a high technical
      success include (1) the use of hydrophilic wires and catheters to traverse
      occlusions in the subintimal plane, (2) femoral access with axially supported
      catheters or sheaths to apply the force needed for successful recanalization, and
      (3) the use of true lumen reentry devices when, after crossing the occlusion, the
      wire or catheter cannot be manipulated into the true lumen beyond the occlusion.

PMID- 16628328
TI  - Commentary on "Crossing chronic total occlusions of the iliac and femoral
      popliteal vessels and the use of true lumen reentry devices".

PMID- 16628330
TI  - Covered stenting of the superficial femoral artery using the Viabahn stent-graft.
AB  - High initial technical success rates for superficial femoral artery
      revascularization are possible using multiple modalities. For these interventions
      to pose a serious challenge to open surgical bypass, improved primary patency in
      mid- and long-term follow-up must be achieved. In several smaller studies,
      covered stenting of the superficial femoral artery has shown superior patency at
      2 years after intervention. The ongoing VIBRANT trial randomizes patients to
      superficial femoral artery intervention with either bare nitinol stents or
      Viabahn covered stents. The 3-year outcomes data from this trial will better
      define the role of percutaneous intervention for complex superficial femoral
      artery disease.

PMID- 16628331
TI  - Commentary on "Covered stenting of the superficial femoral artery using the
      Viabahn stent-graft".

PMID- 16628333
TI  - Plaque excision in the treatment of peripheral arterial disease.
AB  - The goals of any percutaneous intervention in the lower extremity are to provide
      initial technical success and restore durable arterial patency. The first goal
      can be achieved through a multitude of endovascular techniques, whereas achieving
      the latter has remained elusive. The large number of choices in treatment options
      for percutaneous lower-extremity revascularization speak to the fact that no
      single tool or technique has been proven to be superior. The SilverHawk plaque
      excision system is designed to debulk stenotic or occlusive arterial lesions.
      Like many endovascular technologies, reports have focused on rates of initial
      technical success and short-term outcomes, but long-term results remain unknown.
      This report reviews selected published or presented results of plaque excision,
      touches on areas of concern or controversy regarding both the device and some of
      its proponents, and suggests clinical or anatomic settings in which plaque
      excision appears most effective. The ultimate utility of this technology will
      depend on confirmation of its acute and long-term outcomes through unbiased, well
      designed clinical trials.

PMID- 16628334
TI  - Commentary on "Plaque excision in the treatment of peripheral arterial disease".

PMID- 16628336
TI  - Transforming growth factor-beta and wound healing.
AB  - Acute and chronic wounds are a source of significant morbidity for patients, and
      they demand a growing portion of health-care time and finances to be devoted to
      their care. Transforming growth factor-beta (TGF-beta) has surfaced from abundant
      research as a key signal in orchestrating wound repair. In beginning this review,
      we discuss the inflammatory, proliferative, and maturational phases of wound
      healing. We then focus on TGF-beta by first discussing the pathway from its
      production to the target cell where Smad proteins execute an intracellular
      signaling cascade. To review TGF-beta's role in wound healing, we discuss the
      actions of it individually on keratinocytes, fibroblasts, endothelial cells, and
      monocytes, which are the major cell types involved in wound repair. From
      illustrating these cellular actions of TGF-beta, we summarize its multipotent
      role in the process of wound repair. As a clinical correlation, we also review
      research dedicated to the involvement of TGF-beta in venous stasis ulcers.

PMID- 16628337
TI  - Carotid plaque morphologic characteristics.
AB  - Carotid artery atherosclerosis is predominantly believed to mirror
      atherosclerosis elsewhere in the body. Endothelial injury results in expression
      of cell surface adhesion molecules with expression of sequence of genes involved
      in the inflammatory pathway and expression of proinflammatory cytokines. The
      combination of the inflammatory mediators and contribution by monocytes
      infiltrating the intima and vascular smooth muscle cell proliferation result in
      the development of atheromatous plaque with a lipid-rich necrotic core.
      Complications of these atheromatous plaques can lead to plaque instability,
      rupture, and subsequent hemorrhage or ulceration. The significant risk factors,
      characteristics associated with symptoms, and available diagnostic imaging
      modalities are also discussed with review of the relevant literature.

PMID- 16628338
TI  - Commentary. Screening for abdominal aortic aneurysm: recommendation statement.

PMID- 16628340
TI  - Commentary. Carotid artery stents for blunt cerebrovascular injury.

PMID- 16628343
TI  - Commentary. Endovascular aneurysm repair versus open repair in patients with
      abdominal aortic aneurysm (EVAR trial 1): randomized controlled trial.

PMID- 16628344
TI  - Commentary. Endovascular aneurysm repair and outcome in patients unfit for open
      repair of abdominal aortic aneurysm (EVAR trial 2): randomized controlled trial.

PMID- 16628346
TI  - Commentary. Effect of intraoperative fluid management on outcome after
      intraabdominal surgery.

PMID- 16628348
TI  - Commentary. Statins are associated with better outcomes after carotid
      endarterectomy in symptomatic patients.

PMID- 16628352
TI  - Commentary. An evaluation of the efficacy of methods used in screening for lower
      limb arterial disease in diabetes.

PMID- 16628350
TI  - Commentary. Carotid stenting done exclusively by vascular surgeons.

PMID- 16628354
TI  - Developmental regulation of intracellular calcium homeostasis in early cardiac
      myocytes.
AB  - The proper intracellular Ca(2+) signaling is essential for normal cell functions
      and organ development, and the maintaining Ca(2+) homeostasis in cardiac myocytes
      is of functional importance for the intact heart. As the first functional organ
      in the vertebrate embryo, the heart is continuously remodeled and maintains its
      physiologic pumping function in response to increasing circulatory demands. The
      expressions of Ca(2+) handing proteins in the embryonic heart, however, are
      different from those in neonatal and adult hearts, which means that the
      regulation of Ca(2+) transients in embryonic cardiomyocytes is different from
      that in adult cardiac myocytes. Recent advances in molecular and cellular
      biology, as well as the application of embryonic stem cell differentiation
      system, have made progress in uncovering the regulation of Ca(2+) homeostasis
      during cardiomyogenesis. This paper briefly summarizes the Ca(2+) homeostasis
      during early development of cardiomyocytes and reviews current knowledge of the
      regulatory mechanisms controlling Ca(2+) homeostasis during cardiomyocyte
      development.

PMID- 16628355
TI  - Cl- channels: what role do they play in mammalian heart?
AB  - Cl(-) channel has been identified in heart over more than a decade. It is now
      known that Cl(-) channel is a super-family. The potentially important roles of
      cardiac Cl(-) channels have been emerging. Cardiac Cl(-) channels may play
      multifunctional roles in both physiological and pathophysiological conditions.
      Since the existence and distribution of cardiac Cl(-) channels vary with species
      and cardiac tissues, and blockade of Cl (-) channel with putative Cl(-) channel
      blockers or Cl(-) substitution has profound influence on cardiac electrical
      properties, it appears that the main role of cardiac Cl(-) channels may be to
      modulate cation channels or provide an ionic environment suitable for the
      activities of cation channels. So, to investigate the relationship between Cl(-)
      channels and cation channels may be of physiological and pathophysiological
      significance.

PMID- 16628356
TI  - [Inhibitory effects of AcSDKP on proliferation of human bone marrow mesenchymal
      stem cells in vitro].
AB  - The tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a physiological
      regulator of cell proliferation, has been principally reported as a potent
      inhibitor of the proliferation of haematopoietic stem cells and progenitors. The
      purpose of this study was to investigate whether the AcSDKP may directly affect
      the proliferative potential of human bone marrow mesenchymal stem cells (MSCs) in
      vitro. We added AcSDKP to the cultures of human bone marrow mononuclear cells and
      measured the number and average area of MSC colonies. MTT colorimetric assay and
      mitotic index determination were further used to examine the proliferative state
      of the third passage MSCs in subcultures with or without the addition of AcSDKP.
      In addition, we evaluated whether AcSDKP may kill MSCs by the trypan blue dye
      exclusion test. The results showed that the colony forming capacity, the number
      of viable cells and the mitotic index were reduced in human bone marrow MSCs
      cultured in 1x10(-12) mol/L to 1x10(-9) mol/L AcSDKP. Maximum inhibitory activity
      appeared in 1x10(-11) mol/L of AcSDKP. No difference in percent of living cells
      was observed between the MSC subcultures with and without the addition of AcSDKP.
      As a result, AcSDKP within a certain range of concentrations has negatively
      regulatory effects on the proliferation of human bone marrow MSCs in vitro.

PMID- 16628357
TI  - [Simvastatin inhibits hypertension-induced cardiac hypertrophy in rats through
      activation of heme oxygenase-1/carbon monoxide pathway].
AB  - To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight
      male Wistar rats were randomly allocated to four groups. Rats in model group
      received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d)
      by peritoneal injection. Rats in simvastatin treatment groups were given
      simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d)
      intragastrically respectively. Rats in control group received the same volume of
      normal sodium. Left ventricular function, left ventricular mass index (LVMI), the
      content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial
      hydroxyproline and heme oxygenase activity were determined after 6 weeks. The
      results showed that rats in model group developed significant cardiac hypertrophy
      associated with reduced left ventricular function compared with the control
      group. However, compared with the model group, L-NNA-induced cardiac hypertrophy
      of rats was significantly relieved in simvastatin treatment groups, associated
      with improved left ventricular function, decreased LVMI, lower BNP levels in
      plasma and myocardium, lower content of myocardial hydroxyproline, and increased
      myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes,
      simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1)
      mRNA expression, HO activity as well as the production of CO in cardiomyocytes.
      Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not
      change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with
      simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake
      induced by angiotensin II in a concentration-dependent manner. Cotreatment with
      zinc protoporphyrin significantly abolished the suppressive effect of simvastatin
      on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of
      HO-1/CO pathway may be one of the important mechanisms by which statins inhibit
      cardiac hypertrophy caused by hypertension.

PMID- 16628358
TI  - Effects of basic fibroblast growth factor on the expressions of angiogenic gene
      profile and cyclooxygenase-2 in brain microvascular endothelial cells.
AB  - The present study aimed to investigate the effects of basic fibroblast growth
      factor (bFGF) on the expressions of angioge-nesis-related genes in a mouse brain
      microvascular endothelial cell line, namely bEnd.3, using cDNA microarray. The
      effects of bFGF (10 ng/ml) on mRNA and protein expressions of cyclooxygenase-2
      (COX-2), an angiogenesis bystander molecule, were further investigated. cDNA
      microarray was employed to study the effects of bFGF on the expressions of
      angiogenic genes in a high throughput pattern. RT-PCR was used to study the
      effect of bFGF on COX-2 mRNA expression. Western blot and immunocytochemistry
      were utilized to study the effect of bFGF on COX-2 protein expression. The
      results showed that, 2 h after bFGF treatment, pro-angiogenic genes (Adamts1, MMP
      9, Ang-1, PDGF B, G-CSF, FGF16, IGF-1, etc.) were significantly upregulated,
      whereas anti-angiogenic genes (TIMP-2, TSP-3, etc.) were significantly
      downregulated. The bystander molecule in angiogenic pathway COX-2 mRNA and
      protein expressions were significantly upregulated after bFGF treatment. It is
      suggested that triggering angiogensis switch through upregulating pro-angiogenic
      gene and downregulating anti-angiogenic gene expression is one of the major
      mechanisms of bFGF-induced angiogenesis. The expression change of COX-2, as a
      bystander molecule, was observed after bFGF treatment in bEnd.3 cells and the
      significance was discussed.

PMID- 16628359
TI  - [Characteristics of the action potentials and the underlying ionic mechanisms in
      the cardiomyocytes from rabbit pulmonary vein sleeves].
AB  - To investigate the characteristics of action potentials and their ionic mechanism
      in cardiomyocytes from rabbit pulmonary vein sleeves (PVC), and to compare them
      with those in left atrial cardiomyocytes (LAC), the technique of whole-cell patch
      clamp was applied. We used current-clamp technique to record action potentials,
      and voltage-clamp technique to record ionic currents. PVC had longer action
      potential duration (APD) than LAC, and therefore a second plateau response could
      be induced easily, suggesting a strong tendency of early afterdepolarization
      (EAD) genesis in PVC. Non-selective cation current (I(NSCC)) was first recorded
      in both LAC and PVC. This I(NSCC)was permeable to K(+), Na(+) and Cs(+),
      sensitive to GdCl3 but not sensitive to 4-AP. The current densities of inward
      rectifier potassium current (I(K1)), transient outward potassium current (I(To))
      and I(NSCC) were all significantly less in PVC than those in LAC. These
      differences in repolarizing ionic currents between PVC and LAC form a basis of
      the differences in their action potential configurations and might be an
      important ionic mechanism of the arrhythmogenic characteristics of pulmonary vein
      muscle sleeves.

PMID- 16628360
TI  - [Regulative effects of temperature, intracellular sodium, ATP and pH on I(Na/Ca)
      of cardiac myocytes].
AB  - The Na(+)-Ca(2+) exchange is a major pathway for removal of cytosolic Ca(2+) in
      cardiac myocytes. To explore the effects of temperature, intracellular Na(+), ATP
      and pH on Na(+)-Ca(2+) exchange currents (I(Na/Ca)) of intact guinea-pig
      myocytes, the whole-cell patch-clamp technique was used to record I(Na/Ca) in
      isolated guinea-pig ventricular myocytes. We found that I(Na/Ca) at 34 degrees C
      was four times higher than that at 22 degrees C. However, intracellular
      acidification had no obvious influence on bidirectional I(Na/Ca). At 22~24
      degrees C , intracellular ATP depletion and intracellular acidification did not
      markedly affect bidirectional I(Na/Ca) either. At 34~37 degrees C , intracellular
      ATP depletion and intracellular acidification synergistically inhibited the
      outward and inward currents of I(Na/Ca), and blocked the inward currents of
      I(Na/Ca)more potently than the outward currents of I(Na/Ca). The effect of ATP on
      I(Na/Ca) is temperature-dependent. Intracellular higher sodium increased the
      outward currents of I(Na/Ca) however it did not increase, even sometimes
      decreased the inward currents of I(Na/Ca). These results suggest that
      intracellular ATP depletion and intracellular acidification synergistically
      impair Ca(2+) extrusion via forward mode Na(+)-Ca(2+) exchange, and intracellular
      sodium overload increases Ca(2+) influx via reverse mode Na(+)-Ca(2+) exchange,
      leading to calcium overload respectively.

PMID- 16628361
TI  - Different forward masking patterns of sustained noise burst and segmental noise
      burst in the inferior collicular neurons of the mouse.
AB  - Although there has been a growing body of literature showing the neural
      correlation of forward masking caused by a pure tone masker in the auditory
      neurons, relative few studies have addressed the description of how the forward
      masking caused by a noise burst, especially a sequence of noise burst, is
      transformed into neuronal representation in the central auditory system. Using a
      noise forward masking paradigm under free field stimuli conditions, this in vivo
      study was devoted to exploring it in the inferior collicular (IC) neurons of the
      mouse (Mus musculus KM). A total of 96 IC neurons were recorded. Rate-intensity
      functions (RIFs) with and without the presentation of masker, sustained noise
      burst (SNB) or segmental noise burst (SGNB), were measured in 51 neurons. We
      found that the relative masker intensities were distributed over a wide range
      between 21 dB below the minimum threshold (MT) and 19 dB above the MT of the
      corresponding probe tone. The masking effect of the SGNB on firing rate in nearly
      half of neurons (type I, 45.10%) was stronger than that of the SNB (P<0.001),
      whereas in a smaller fraction of neurons (type III, 17.65%), it was weaker than
      that of the SNB (P<0.001). There was no significant difference in masking effect
      between the SNB and SGNB in type II neurons (37.25%, P>0.05). Irrespective of
      type I or type III neurons, the inhibitory effects of both kinds of maskers were
      all greater at lower probe intensities but decreased significantly with the
      increase of probe intensity (P<0.001). Interestingly, as the probe intensity
      increased, the difference of masking effect between the SNB and SGNB disappeared
      (P>0.05). In addition, we observed that temporal masking pattern could be
      transformed when the masker was changed from the SNB to SGNB. The main type of
      this transformation was from early-inhibition to proportional-inhibition pattern
      (53.85%, 7/13). Our data provide the evidence that the inhibitory effects of
      these two maskers have differential weights over time and intensity domains of
      the IC neurons responding to a pure tone. This suggests that the forward masking
      of noise is by no means the source of simply suppression in neuronal firing rate.
      There might be a few of active neural modulating ways in which the coding of
      temporal acoustical information can be operated.

PMID- 16628362
TI  - [Capacitative Ca2+ entry is involved in ACh-induced distal colon smooth muscle
      contraction in rats].
AB  - Contraction of smooth muscle cells is triggered by an increase in cytosolic
      Ca(2+) upon agonist stimulation. Ca(2+) influx across the plasma membrane
      constitutes a major component of the agonist-induced response in smooth muscle
      cells. Traditionally, voltage-operated Ca(2+) channel (VOCC) is considered as the
      channel mediating the Ca(2+) entry. However, this view has been challenged by
      recent discoveries, which demonstrated that other types of ion channels, such as
      store-operated and/or receptor-operated Ca(2+) channels (SOCC and/or ROCC), also
      participate in Ca(2+) response induced by agonists in smooth muscle cells. SOCC
      is defined as the channel activated in response to the depletion of the internal
      Ca(2+) stores, an event secondary to G protein coupled receptor or receptor
      tyrosine kinase stimulation. The Ca(2+) flow mediated by SOCC is termed as
      capacitative Ca(2+) entry (CCE). Previous study from other group has demonstrated
      that VOCC played a predominant role in ACh-induced contraction of distal colon
      smooth muscle in guinea pig. However, whether SOCC participates in the agonist
      induced contractile response in this particular tissue is unknown. The present
      study was performed to investigate the role of CCE in ACh-induced mechanical
      activity of distal colon smooth muscle in rats. The contractile function of the
      smooth muscle was assessed by measuring isometric force of isolated rat distal
      colon rings. We showed that both high extracellular K(+) (40 mmol/L) and ACh (5
      mumol/L) evoked striking contraction of the smooth muscle. The contractile
      responses were almost abolished by removal of extracellular Ca(2+) with ethylene
      glycol-bis(2-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), suggesting a
      critical contribution of extracellular source of Ca(2+) to the contraction.
      Verapamil (5 mumol/L), an L-type VOCC blocker, significantly attenuated, but
      didn't completely eliminate the high K(+)- and ACh-induced contraction (74% and
      41% for high K(+) and ACh, respectively), indicating that additional channels
      might be involved in the contractile mechanism. Furthermore, ACh only induced
      transient contractions in the absence of extracellular Ca(2+). Readmission of
      Ca(2+) into the extracellular compartment resulted in a significant and sustained
      increase in the tension of the smooth muscle. This response was not affected by
      verapamil (5 mumol/L) and Cd(2+) (5 mumol/L), both of which efficiently block
      VOCC at the doses. However, La(3+), a known inhibitor of SOCC, significantly
      suppressed the Ca(2+) readdition-induced contraction in a dose-dependent manner.
      On the basis of these results, we conclude that contraction of smooth muscle in
      the distal colon is regulated by multiple Ca(2+) channels. In addition to VOCC
      mediated Ca(2+) influx, SOCC-mediated CCE participates in agonist-induced
      contractile response of distal colon smooth muscle in rats.

PMID- 16628363
TI  - [Cation ions modulate the ACh-sensitive current in type II vestibular hair cells
      of guinea pigs].
AB  - Molecular biological studies and electrophysiological data have demonstrated that
      acetylcholine (ACh) is the principal cochlear and vestibular efferent
      neurotransmitter among mammalians. However, the functional roles of ACh in type
      II vestibular hair cells among mammalians are still unclear, with the exception
      of the well-known alpha9-containing nicotinic ACh receptor (alpha9-nAChR) in
      cochlear hair cells and frog saccular hair cells. In this study, the properties
      of the ACh-sensitive current were investigated by whole-cell patch clamp
      technique in isolated type II vestibular hair cells of guinea pigs. The direct
      effect of extracellular ACh was to induce a hyperpolarization effect in type II
      vestibular hair cells. Type II vestibular hair cells displayed a sustained
      outward current in response to the perfusion of ACh. It took about 60 s for the
      ACh-sensitive current to get a complete re-activation. The reversal potential of
      the ACh-sensitive current was (-66 +/- 8) mV, which indicated that potassium ion
      was the main carrier of this current. The blocking effect by the submillimolar
      concentration of tetraethylammonium (TEA) further indicated that extracellular
      ACh stimulated the calcium-dependent potassium current. Following replacement of
      the compartment of NaCl in the normal external solution with TrisCl, LiCl or
      saccharose respectively, the amplitude of the ACh-sensitive current was not
      affected. Blocking of the release of intracellular Ca(2+) stores by intracellular
      application of heparin failed to inhibit the ACh-sensitive current. Therefore,
      extracellular Na(+)and the inositol 1,4,5-trisphosphate (IP(3))-dependent
      intracellular Ca(2+)release were not involved in the activation of the ACh
      sensitive current. However, the ACh-sensitive current was strongly affected by
      the concentration of the extracellular K(+), extracellular Ca(2+) and
      intracellular Mg(2+). The amplitude of the ACh- sensitive current was strongly
      inhibited by high concentration of extracellular K(+). In the Ca(2+)-free
      external solution, ACh only activated a very small current; however, the ACh
      sensitive current demonstrated a Ca(2+)-dependent inhibition effect in high
      concentration of Ca(2+)solution. In addition, the ACh-sensitive current was
      inhibited by increasing of the concentration of intracellular Mg(2+). In
      conclusion, the present results demonstrate that ACh plays an important role in
      the vestibular efferent system. The fact that Na(+) is not involved in the ACh
      sensitive current will not favor the well-known profile of alpha9-nAChR, which is
      reported to display a small but important permeability to Na(+). It is also
      suggested that, in vivo, the amplitude of the ACh-induced hyperpolarization may
      strongly depend on the concentration of extracellular Ca(2+)and intracellular
      Mg(2+).

PMID- 16628364
TI  - Characteristics of P2X purinoceptors in the membrane of rat trigeminal ganglion
      neurons.
AB  - The characteristics of purinoceptors in the membrane of rat trigeminal ganglion
      (TG) neurons were studied by using whole- cell patch clamp technique. The results
      showed that most of neurons examined (78.9%, 142/180) were responsive to ATP in a
      concentration-dependent manner; the others (21.1%, 38/180) were ATP insensitive.
      Of the ATP-sensitive cells, the majority (95.1%, 135/142) responded to ATP with
      an inward current, a few (2.1%, 3/142) with an outward current, and the rest
      (2.8%, 4/142) with biphasic current. Small sized cells (<30 mum) responded to ATP
      with a rapid desensitizing inward current and were highly sensitive to vanilloid;
      the medium sized cells (30~40 mum) responded to ATP with slow desensitizing
      inward current and were not sensitive to vanilloid; while the majority of large
      sized cells (>40 mum) did not respond to ATP and vanilloid. The waveform of ATP
      activated inward currents was related to the cell diameter. The I-V curves for
      both small and medium sized cells manifested obvious inward rectification.
      Furthermore, we studied the kinetic features of ATP-activated currents and the
      effects of P2 purinoceptor agonists and antagonists on I(ATP). The findings
      suggest that ATP receptor-ion channels are expressed differently among different
      types of rat TG neurons.

PMID- 16628365
TI  - Intraganglionic laminar endings act as mechanoreceptors of vagal afferent nerve
      in guinea pig esophagus.
AB  - Intraganglionic laminar endings (IGLEs) have been supposed to be the
      mechanoreceptors in the gut by electrophysiological recording techniques. But the
      specialized morphology of IGLEs could not be displayed closely associated with
      this function and the mechanism that IGLEs act as the mechanotransduction sites
      in the gut is not yet well understood. In the present study, we used styryl dye
      FM1-43 combined with stretch stimulation in the guinea pig esophagus to test
      whether IGLEs acted as the mechano-sensitive receptors of the vagal afferent
      nerves. At the same time, the special structure of IGLEs displayed by FM1-43 was
      further confirmed by neurobiotin anterograde labeling technique. To further
      investigate the characteristics of IGLEs as mechanosensitive receptors, different
      drugs were used to block or stimulate IGLEs activation. Our results indicated
      that only in the stretched preparation could FM1-43 enter the IGLEs and
      completely display their specialized structure, which was consistent with that
      shown by neurobiotin. The amount of IGLEs shown by stretch-evoked FM1-43 staining
      was much more than that shown without stretch stimulation [(90.4 +/- 9.5) % vs
      (10.7 +/- 2.1) %, P<0.05]. Ca(2+), TTX (0.6 mumol/L), atropine (0.6 mumol/L), SKF
      (50 mumol/L), and gadolium (100 mumol/L) had no effect on the IGLEs activation.
      But for benzamil (100 mumol/L), an epithelial sodium channel blocker, activation
      of IGLEs by stretch stimulation was significantly blocked. The potent ATP
      analogue, alpha,beta-methylene ATP (100 mumol/L) could not activate FM1-43
      staining without stretch. These results indicate that IGLEs are sensitive to
      mechanical stimulation. This could lead to the deduction that IGLEs act as the
      mechanoreceptors of vagal afferent nerve. IGLEs could transmit mechanical stimuli
      directly through ion channels, independent of neurotransmitter release and action
      potential propagation. The stretch-sensitive channels on IGLEs probably belong to
      the epithelial sodium channel family rather than voltage-gated sodium ion
      channels. Furthermore, styryl dye FM1-43 is a useful activity-dependent marker to
      demonstrate the structure and function of IGLEs in guinea pig esophagus.

PMID- 16628366
TI  - [Changes of glutamate and taurine released in the medial vestibular nucleus
      following acute hypotension].
AB  - In order to understand whether some special amino acids in the medial vestibular
      nucleus (MVN) of rats are involved in the regulation of blood pressure, we used
      microdialysis technique and high performance liquid chromatography (HPLC) to
      measure the changes of glutamate and taurine in this central area. Acute
      hypotension was induced by hemorrhage from the femoral artery. It was observed
      that the basal release of glutamate and taurine in the MVN was stable about 90
      min after the beginning of microdialysis. The basal release of glutamate was
      (18.96 +/- 0.27) pmol/sample (8 mul), and that of taurine was (7.73 +/- 0.05)
      pmol/sample (8 mul). Glutamate release increased (P<0.05) and taurine release
      reduced (P<0.05) in the MVN in the hemorrhage-induced acute hypotensive rats.
      Nevertheless, these changes were not observed in the hemorrhage-induced acute
      hypotensive rats which were pretreated by infusing 2% lidocaine into the middle
      ear or 100 mg arsanilic acid into the tympanic cavity. These results suggest that
      the hemorrhage-induced acute hypotention can influence the activity of the
      neurons in the MVN by the afferent impulses from vestibular organ, and that some
      special amino acid transmitters in the MVN are involved in this process.

PMID- 16628367
TI  - A remote controlled multimode micro-stimulator for freely moving animals.
AB  - This paper presents a remote controlled multimode micro-stimulator based on the
      chip nRF24E1, which consists mainly of a micro-control unit (MCU) and a radio
      frequency (RF) transceiver. This micro-stimulator is very compact (18 mmx28 mm
      two layer printed circuit board) and light (5 g without battery), and can be
      carried on the back of a small animal to generate electrical stimuli according to
      the commands sent from a PC 10 meters away. The performance and effectiveness of
      the micro-stimulator were validated by in vitro experiments on the sciatic nerve
      (SN) of the frog, where action potentials (APs) as well as artifacts were
      observed when the SN was stimulated by the micro-stimulator. It was also shown by
      in vivo behavioral experiments on operant conditioned reflexes in rats which can
      be trained to obey auditory instruction cues by turning right or left to receive
      electrical stimulation ('virtual' reward) of the medial forebrain bundle (MFB) in
      a maze. The correct response for the rats to obey the instructions increased by
      three times and reached 93.5% in an average of 5 d. This micro-stimulator can not
      only be used for training small animals to become an 'animal robot', but also
      provide a new platform for behavioral and neurophysiological experiments.

PMID- 16628368
TI  - A mathematical model for constituent ratios of energy expenditure in human.
AB  - In order to assess the constituent ratios of energy expenditure in human, the
      deductive process of establishing a mathematical model for assessing the
      constituent ratios of the three major nutrients in energy expenditure in human
      was described in this paper. Total oxygen consumption, total carbon dioxide
      output and total nitrogen (urine nitrogen + skin nitrogen) excretion are related
      to the oxidation of the three major nutrients and the physiological combustion
      values of the three nutrients are already known. Based on these measurable and
      known parameters, the mathematical model established by the authors will help
      understand the characteristics of the tested individual's energy expenditure.

PMID- 16628369
TI  - Sex differences in perception of emotion intensity in dynamic and static facial
      expressions.
AB  - Most research on the perception of emotional expressions is conducted using
      static faces as stimuli. However, facial displays of emotion are a highly dynamic
      phenomenon and a static photograph is its very unnatural representation. The goal
      of the present research was to assess the role of stimuli dynamics as well as
      subjects' sex in the perception of emotional expressions. In the experiment,
      subjects rated the intensity of expressions of anger and happiness presented as
      photographs (static stimuli) and animations (dynamic stimuli). The impact of both
      stimulus dynamics and emotion type on the perceived intensity was observed. The
      emotions on 'angry faces' were judged as more intense than on 'happy faces' and
      the intensity ratings were higher in the case of animation rather than
      photography. Moreover, gender differences in the rated intensity were found. For
      male subjects higher intensity ratings for dynamic than for static expressions
      were noted in the case of anger, whereas in the case of happiness, no differences
      were observed. For female subjects, however, differences for both anger and
      happiness were significant. The results suggest that the dynamic characteristic
      of facial display is an important factor in the perception of the intensity of
      emotional expressions. Its effect, however, depends on the subjects' sex and
      emotional valence.

PMID- 16628372
TI  - Vesicovaginal fistula following a transobturator midurethral sling procedure.
AB  - Synthetic mid-urethral slings are currently the most common surgical procedure
      performed for the treatment of female stress urinary incontinence. The
      transobturator mid-urethral sling technique was originally described in 2001 and
      has since become widely accepted due to its high rate of success and low
      complication rate. Although complications remain infrequent, when they do occur,
      there is potential for significant patient morbidity. We report a case of a
      vesicovaginal fistula following a transobturator mid-urethral sling procedure and
      describe successful reconstruction with transvaginal sling excision, fistula
      closure, and placement of an autologous pubovaginal sling.

PMID- 16628373
TI  - Incidence of stress urinary incontinence among women in Turkey.
AB  - The aim of this study was to determine the incidence of stress urinary
      incontinence among women at the age of 15 and above who applied to the primary
      health care centers in Ankara, Turkey. We applied the urinary stress incontinence
      questionnaire to 2,601 women at the age of 15 or above who consulted to the
      "mother-child health care and family planning centers" in January 2002. To
      evaluate the urinary incontinence status with respect to age groups and other
      risk factors, chi-square test was used. Stress incontinence prevalence was 16.1%
      in our population. Age was a statistically significant risk factor affecting the
      incidence of stress incontinence. As the number of gravida increases, the
      frequency of stress incontinence increases (p<0.05). Presence of a systemic
      disease was also an important risk factor (p<0.05). Alcohol use and smoking were
      not found to affect the incidence of urinary stress incontinence (p>0.05). As
      urinary incontinence greatly influences life quality and social and psychological
      status of the person, and also creates economic burden, predisposing factors of
      stress incontinence should be well defined and measures should be taken to
      encourage women experiencing this problem to visit a doctor and to get an
      efficient treatment.

PMID- 16628374
TI  - A 3-month preclinical trial to assess the performance of a new TVT-like mesh
      (TVTx) in a sheep model.
AB  - The objective of this study was to evaluate in a sheep model the performance of a
      new polypropylene mesh (TVTx), which is intended as a less invasive treatment for
      female stress urinary incontinence. Eight female sheep were used in this study,
      each one being implanted with eight TVTx samples. At each time-point (weeks 1, 2,
      4, and 12) seven TVTx were pulled out, while one TVTx was carefully dissected for
      histological investigations. One TVTx and one TVT, moreover, were inserted and
      immediately pulled out for obtaining the initial pullout forces in all sheep. The
      initial pullout values of TVT and TVTx were overlapping. The pullout forces of
      TVTx were >5 N (500 g) and increasing from weeks 1 to 12 (p<0.001). Histology
      revealed good tissue integration of TVTx in the tissue within 12 weeks after
      implantation. No abnormal histological findings were observed. This data could
      support the realization of a clinical trial with the TVTx mesh.

PMID- 16628375
TI  - The effect of vaginal and cesarean delivery on lower urinary tract symptoms: what
      makes the difference?
AB  - A prospective cohort study was undertaken to evaluate the effect of pregnancy and
      childbirth in nulliparous pregnant women. The focus of this paper is on the
      difference in the prevalences and risk factors for lower urinary tract symptoms
      (LUTS) between woman who delivered vaginally or by cesarean and secondly the
      effect of LUTS on the quality of life between these two groups was analyzed.
      Included were 344 nulliparous pregnant women who completed four questionnaires
      with the Urogenital Distress Inventory and the Incontinence Impact Questionnaire
      (IIQ). Two groups were formed: vaginal delivery group (VD), which included
      spontaneous vaginal delivery and an instrumental vaginal delivery and cesarean
      delivery group (CD). No statistical significant differences were found in the
      prevalences of LUTS during pregnancy between the two groups. Three months after
      childbirth, urgency and urge urinary incontinence (UUI) are less prevalent in the
      CD group, but no statistical difference was found 1 year postpartum. Stress
      incontinence was significantly more prevalent in the VD group at 3 and 12 months
      postpartum. The presence of stress urinary incontinence (SUI) in early pregnancy
      is predictive for SUI both in the VD as in CD group. A woman who underwent a CD
      and had SUI in early pregnancy had an 18 times higher risk of having SUI in year
      postpartum. Women were more embarrassed by urinary frequency after a VD. After a
      CD, 9% experienced urge urinary incontinence. Urge incontinence affected the
      emotional functioning more after a cesarean, but the domain scores on the IIQ
      were low, indicating a minor restriction in lifestyle. In conclusion, after
      childbirth, SUI was significantly more prevalent in the group who delivered
      vaginally. Besides a vaginal delivery, we found both in the VD and in the CD
      group that the presence of SUI in early pregnancy increased the risk for SUI 1
      year after childbirth. Further research is necessary to evaluate the effect of
      SUI in early pregnancy on SUI later in life. Women were more embarrassed by
      urinary frequency after a vaginal delivery. UUI after a CD compared to a vaginal
      birth limited the women more emotionally; no difference was found for the effect
      of SUI on the quality of life between the two groups.

PMID- 16628377
TI  - Heliorestis convoluta sp. nov., a coiled, alkaliphilic heliobacterium from the
      Wadi El Natroun, Egypt.
AB  - A morphologically distinct heliobacterium, strain HH, was isolated from Lake El
      Hamra, a soda lake in the Wadi El Natroun region of northwest Egypt. Strain HH
      consisted of ring-shaped cells that remained attached after cell division to
      yield coils of various lengths. Strain HH showed several of the physiological
      properties of known heliobacteria and grouped in the Heliorestis clade by virtue
      of its phylogeny and alkaliphily. The closest relative of strain HH was the
      filamentous alkaliphilic heliobacterium Heliorestis daurensis. However, genomic
      DNA:DNA hybridization results clearly indicated that strain HH was a distinct
      species of Heliorestis. Based on its unique phenotypic and genetic properties we
      describe strain HH here as a new species of the genus Heliorestis, H. convoluta
      sp. nov.

PMID- 16628378
TI  - Changes in hydrophilic antioxidant activity in Avena sativa and Triticum aestivum
      leaves of different age during de-etiolation and high-light treatment.
AB  - The steady-state of reactive oxygen species (ROS) in plant cells is controlled by
      ROS-producing and scavenging agents. A large cellular pool of antioxidant
      metabolites is involved in their control. Variations in this antioxidant pool may
      be monitored by measuring changes in hydrophilic antioxidant activity (free
      radical-quenching activity of water-soluble components) and ascorbic acid levels.
      The de-etiolation process and induction of light stress in Avena sativa and
      Triticum aestivum leaves were used as physiological models to study the
      antioxidant status at different ages. The data showed that five-day-old green
      plants and de-etiolated plants of the same age have similar hydrophilic
      antioxidant activity ( approximately 8 mumol ASC equivalents g FW(-1)), which
      increases during the de-etiolation process. In oat and wheat, young leaves (five
      days old) had higher antioxidant status (hydrophilic antioxidant activity and
      ascorbic acid level) than old leaves (10 and 20 days old). High-light treatment
      caused a decrease in antioxidant status, especially in young leaves. Hydrophilic
      antioxidant activity and ascorbic acid levels recovered totally or partially
      after 30 or 60 min in the dark. This capacity also depends on age and species.
      The ascorbic acid/hydrophilic antioxidant activity ratio is presented as an
      indicator of antioxidant variations in response to stress, but taking into
      account the absolute levels of antioxidants.

PMID- 16628379
TI  - Stand structure and woody species diversity in relation to stand stratification
      in a subtropical evergreen broadleaf forest, Okinawa Island.
AB  - Stand structure and woody species diversity in a subtropical evergreen broadleaf
      forest grown in a silicate habitat, Okinawa Island, have been investigated on the
      basis of stand stratification. The forest stand consisted of four layers. The
      floristic composition of the top and the lower three layers was only slightly
      similar, although approximately one-third of the species were common to them.
      Mean tree weight decreased from the top toward the bottom layer whereas tree
      density increased from the top downward. This trend resembled the mean weight
      density trajectory of self-thinning plant populations. The relationship between
      mean tree height and tree density for the upper two layers supported Yamakura's
      quasi -1/2 power law of tree height. The values of the Shannon-Wiener index, H',
      and the equitability index, J', tended to increase from the top layer downward
      except for the bottom layer. The values of H' and J' were, respectively, 4.83 bit
      and 0.82 for trees taller than 0.10 m. The lower layers contained many species of
      smaller height. High species diversity of the forest depended on small trees in
      the lower layers. Conservation of small trees in the lower layers, especially the
      bottom layer, is indispensable for sound maintenance of Okinawan evergreen
      broadleaf forests.

PMID- 16628380
TI  - Functional morphology of phonation evaluated by dynamic MRI.
AB  - The complex anatomy of the larynx is a consequence of its various airway
      functions. The aim of the present study was to evaluate which anatomical
      structures of the larynx soft tissues could be defined using MRI, and to
      investigate the feasibility of using this technique to assess the dynamic
      functions of the larynx. MRI images of the larynx of six healthy volunteers
      during speech production were obtained in vivo. The volunteers were asked to
      breathe out long and deep in order to prolong in a normal voice the emission of
      the vowels [i] (as in key) and [a] (as in car) and the consonant [ch] (as in
      ship). We demonstrated the modification of the larynx position, which is high for
      [i] and low for [a], and the modification of the vocal folds which is adducted
      and abducted in [i] and kept abducted in [ch]. Dynamic MRI allows the possibility
      of multiplanar high-resolution imaging. It can provide information about the
      anatomy of the larynx and, it also has the ability to image moving laryngeal
      structures and to analyze vocal fold vibrations during phonation.

PMID- 16628381
TI  - Pericardiacophrenic shunt: imaging finding of rare splenosystemic collateral.
      Case report.
AB  - Portosystemic collaterals are the natural consequence of portal hypertension.
      These collaterals can occur anywhere in the gastrointestinal tract. Apart from
      the usual sites, they can develop in some unusual and rare locations. In this
      report, imaging findings of an unusual venous collateral pathway between spleen
      and left subclavian vein in a 30-year-old female patient with cirrhosis and
      portal hypertension are presented.

PMID- 16628382
TI  - Non-invasive diagnosis of in stent stenosis by stress 99m technetium tetrofosmin
      myocardial perfusion imaging.
AB  - BACKGROUND: The aim of this study was to assess the accuracy of stress 99m
      technetium tetrofosmin myocardial perfusion imaging for the diagnosis of in stent
      stenosis (ISS). METHODS: We studied 72 patients who underwent exercise or
      dobutamine stress 99m technetium tetrofosmin imaging, 0.9+/-0.5 years after
      percutaneous coronary interventions in which stents were deployed. Coronary
      angiography was performed within 3 months of the stress test. ISS was defined as
      > or =50% stenosis in a coronary segment with previous stenting. Significant
      coronary artery disease (CAD) was defined as > or =50% stenosis within or outside
      the stented coronary segment. RESULTS: The stent was deployed in 1 coronary
      artery in 52 patients, and in 2 coronary arteries in 20 patients (a total of 92
      detected in 42 (58%) patients (51 stents). Reversible perfusion abnormalities
      were present in 34 of patients with ISS (sensitivity=81%, CI 70-94). Regional
      sensitivity for diagnosis of stenosis per stent was 76% (CI 65-88), specificity
      was 83% (CI 71-94) and accuracy was 79% (CI 69-85). Reversible perfusion
      abnormalities were detected in > or =2 vascular distributions in 15 of 22
      patients with multi-vessel CAD and in 5 of 50 patients without (sensitivity for
      identifying multivessel CAD=68%, CI 50-89; specificity=90%, CI 82-98; and
      accuracy=83%, CI 75-90). CONCLUSION: Stress 99m technetium tetrofosmin myocardial
      perfusion imaging is a useful non-invasive technique for the diagnosis of in
      stent stenosis and extent of CAD in patients with previous percutaneous coronary
      artery interventions.

PMID- 16628383
TI  - Asymptomatic partial anomalous pulmonary venous return masquerading as pulmonary
      vein occlusion following radiofrequency ablation.
AB  - Recent advances in the field of cardiac electrophysiology have resulted in the
      rapid growth of radiofrequency ablation for treatment of arrhythmias. Pulmonary
      vein stenosis or occlusion is a rare, but well described adverse outcome.
      Fortunately, the concomitant evolution of multislice computed tomography (CT)
      scanners has provided an excellent non-invasive method of monitoring for this
      complication. We recently encountered a case on multislice CT that initially
      appeared to be a pulmonary vein occlusion related to the procedure, but on
      further evaluation was found to be an asymptomatic case of partial anomalous
      pulmonary venous return.

PMID- 16628384
TI  - Depressed heart rate response to vasodilator stress for myocardial SPECT predicts
      mortality in patients after myocardial infarction.
AB  - BACKGROUND: As heart rate (HR) response during vasodilator stress myocardial
      perfusion studies can be a marker of HR variability, we investigated its
      prognostic value in patients after myocardial infarction (MI). METHODS: Subjects
      were 147 survivors of MI who underwent vasodilator stress thallium-201
      scintigraphy. HR response was measured as peak to basal (P/B) ratios during
      vasodilator infusion. End points for survival analysis were all-cause deaths, non
      fatal recurrent MI, and soft events. RESULTS: HR response was significantly
      depressed in the post-MI patients compared to controls (p<0.0005). HR response
      correlated to LVEF (r=0.37, p<0.0001) and summed stress scores (r=-0.18, p<0.05),
      but not with antianginal medication. During 58+/-30 mo of follow-up, there were
      15 deaths, 7 recurrent MI, and 11 soft events. Low HR response, old age, low
      LVEF, and high difference score were significant univariate risk factors for
      death. Multivariate analysis identified low HR response (p=0.03), high stress
      score (p=0.02), and low LVEF (p=0.05) as independent predictors of mortality. The
      predictive value of HR response was incremental to that offered by other
      variables (p=0.02). CONCLUSIONS: HR response, readily attained during vasodilator
      stress myocardial perfusion studies, may provide useful additional prognostic
      information in post-MI patients.

PMID- 16628387
TI  - ROC analysis for diagnostic accuracy of fracture by using different monitors.
AB  - BACKGROUND: The purpose of this study was to compare diagnostic accuracy by using
      two types of monitors. METHODS: Four radiologists with 10 years experience twice
      interpreted the films of 77 fracture cases by using the ViewSonic P75f+ and BARCO
      MGD221 monitors, with a time interval of 3 weeks. Each time the radiologists used
      one type of monitor to interpret the images. The image browser used was the
      Unisight software provided by Atlastiger Company (Shanghai, China), and
      interpretation result was analyzed via the LABMRMC software. RESULTS: In studies
      of receiver operating characteristics to score the presence or absence of
      fracture, the results of images interpreted through monochromic monitors showed
      significant statistical difference compared to those interpreted using the color
      monitors. CONCLUSION: A significant difference was observed in the results
      obtained by using two kinds of monitors. Color monitors cannot serve as
      substitutes for monochromatic monitors in the process of interpreting computed
      radiography (CR) images with fractures.

PMID- 16628388
TI  - Computerized digital imaging techniques provided by digital X-ray radiogrammetry
      as new diagnostic tool in rheumatoid arthritis.
AB  - PURPOSE: Our study evaluates digital x-ray radiogrammetry (DXR) and
      Radiogrammetry Kit (RK) as a new diagnostic method for the measurement of disease
      related osteoporosis including quantification of joint space narrowing dependent
      on the severity of rheumatoid arthritis (RA). MATERIALS AND METHODS: A total of
      172 unselected patients with RA underwent computerized measurements of bone
      mineral density (BMD) and metacarpal index (MCI) by DXR, as well as a
      semiautomated measurement of joint space distances at the metacarpal-phalangeal
      articulation (JSD-MCP 2-5), both were analyzed from plain radiographs of the
      nondominant hand. RESULTS: Correlations between DXR-BMD and DXR-MCI vs.
      parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected
      negative association was observed between RK parameters and the different scoring
      methods (-0.27 < R < -0.59). The maximum relative decrease in BMD vs. MCI as
      measured by DXR between the highest and lowest RA severity group was -27.7% vs. 
      27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of
      relative DXR-BMD and DXR-MCI reduction could be documented for the Sharp Erosion
      Score (-20.8% vs. -26.8%; p < 0.01). The relative reduction of mean JSD-MCP using
      RK significantly varied from -25.0% (Sharp Erosion Score) to -41.2% (modified
      Larsen Score). In addition, an excellent reproducibility of DXR and RK could be
      verified. CONCLUSION: DXR in combination with RK could be a promising, widely
      available diagnostic tool to supplement the different scoring methods of RA with
      quantitative data, allowing an earlier and improved diagnosis and more precision
      in determining disease progression.

PMID- 16628397
TI  - Cerebral acetylcholine and choline contents and turnover following low-dose
      acetylcholinesterase inhibitors treatment in rats.
AB  - Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking
      water plus subcutaneous (s.c.) saline (0.5 ml/kg) injections three times/week,
      (2) pyridostigmine bromide (PB) in drinking water (80 mg/L) plus s.c. saline
      injections three times/week, (3) regular tap drinking water plus s.c. sarin (0.5
      x LD(50)) injections three times/week, or (4) PB in drinking water plus s.c.
      sarin injections three times/week. Repeated doses of sarin, in the presence or
      absence of PB, were devoid of acute toxicity during the three-week treatment
      period. Two, 4, and 16 weeks post-treatment, animals were given an intravenous
      pulse injection of choline labeled with 4 deuterium atoms (D4Ch) followed, after
      1 min, by microwave fixation of the brain in vivo. Tissue levels of endogenous
      acetylcholine (D0ACh), endogenous choline (D0Ch), D4Ch, and ACh synthesized from
      D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry in
      hippocampus, infundibulum, mesencephalon, neocortex, piriform cortex, and
      striatum. Ch uptake from blood and ACh turnover were estimated from D4Ch and
      D4ACh concentrations in brain tissue, respectively. Statistically significant
      differences among brain regions were found for D0Ch, D4Ch, D0ACh and D4ACh at 2,
      4 and 16 weeks post-treatment. However, differences in the values of these
      parameters between control and drug treatments were found only for D0ACh and D0Ch
      at 2 and 4 weeks, but not at 16 weeks post-treatment. In conclusion, the results
      from these experiments do not support a delayed or persistent alteration in
      cholinergic function after exposure to low doses of PB and/or sarin.

PMID- 16628398
TI  - [The cemented MS-30 stem. A multi-surgeon series of 333 consecutive cases].
AB  - INTRODUCTION: So far there is only one peer-reviewed long-term publication from
      the inventors' clinic for the MS-30 stem. MATERIAL AND METHODS: In a
      retrospective study we followed the first 333 consecutive MS-30 stems. All
      patients with 5- to 11-year follow-up were clinically and radiographically
      evaluated. At the time of implantation the criteria of modern cementing
      techniques were not implemented. Clinical evaluation was done using the scores of
      Harris and Merle d'Aubigne and Postel. Radiographic evaluation included quality
      of the cement mantle (true lateral radiographs taken under fluoroscopy), stem
      subsidence, loosening signs, and the risk for pending failure. RESULTS: At follow
      up 12 hips had undergone femoral revision: 3 for aseptic loosening, 6 for
      infection, 1 for periprosthetic fracture, and 2 for recurrent dislocation. The
      overall survival for all reasons at 10 years was 96.1%; survival with aseptic
      loosening as an end point was 99.0%. The median Harris Hip Score at follow-up was
      80 (26-100) points. Radiological evaluation revealed a thin cement mantle (<2 mm)
      in approximately 2/3, predominantly on the lateral views (Gruen zones 8/9). One
      third of all reviewed prostheses were considered at risk for pending failure,
      which strongly correlated with the initial quality of the cement mantle.
      CONCLUSION: Midterm results with the MS-30 stem are encouraging and an even
      better long-term outcome can be expected with a better cement technique.

PMID- 16628399
TI  - Selective attention and Pavlovian conditioning.
AB  - The present results show that the common practice of using self-indexing
      conditioned stimuli (CSs) in research on Pavlovian conditioning is a major source
      of experimental bias. The typical stimulus used is either a light flash or a
      sound pulse in a light/sound-shielded chamber. Under these conditions the onset
      characteristics of the CS signal totally predominate over the durational
      characteristic, i.e. the pattern information. Thus a visual pattern presented as
      a CS in a dark chamber is confounded with a brightness change from darkness to
      light. In the first experiment, animals were conditioned with a brightness CS
      using a self-indexing signal paradigm. When tested for specificity of the
      conditioning, they showed complete transfer of learning to either a visual
      pattern or even an auditory CS. These findings indicated that the traditional
      conditioning paradigm is biased towards non-specific sensory learning. The second
      experiment showed that specific sensory conditioning is critically dependent on
      selective attention mechanisms. When the onset characteristics of the CS signal
      were de-emphasized by the use of equal energy background illumination in the
      intertribal interval (ITI) during conditioning, the animals were not able to
      feature extract either the onset or the durational component of the CS signal
      from the ITI background despite prolonged training. It was only by starting with
      conditioning that was initially anchored to the CS onset characteristics that a
      perceptual fade-in procedure would bias attention to feature extract the
      durational characteristics of the CS. Thus conditioning occurred only when the
      rabbit's attention was directed to detection of the gratings display without any
      associated changes in visual albedo. Perhaps the most important finding of the
      present experiments is that the use of self-indexing CS signals in Pavlovian
      conditioning inevitably introduces non-specific sensory processing involving
      multiple sensory input pathways in the conditioning. This inherent uncertainty of
      the sensory input pathways presents a problem for clarifying the role of sensory
      pathways in the neural mechanisms of NM conditioning. In addition, the use of
      self-indexing CSs inevitably leads to an underestimation of the role of forebrain
      mechanisms in Pavlovian conditioning.

PMID- 16628400
TI  - Mechanisms of human static spatial orientation.
AB  - We have developed a tri-axial model of spatial orientation applicable to static
      1g and non-1g environments. The model attempts to capture the mechanics of
      otolith organ transduction of static linear forces and the perceptual
      computations performed on these sensor signals to yield subjective orientation of
      the vertical direction relative to the head. Our model differs from other
      treatments that involve computing the gravitoinertial force (GIF) vector in three
      independent dimensions. The perceptual component of our model embodies the idea
      that the central nervous system processes utricular and saccular stimuli as if
      they were produced by a GIF vector equal to 1g, even when it differs in
      magnitude, because in the course of evolution living creatures have always
      experienced gravity as a constant. We determine just two independent angles of
      head orientation relative to the vertical that are GIF dependent, the third angle
      being derived from the first two and being GIF independent. Somatosensory
      stimulation is used to resolve our vestibular model's ambiguity of the up-down
      directions. Our otolith mechanical model takes into account recently established
      non-linear behavior of the force-displacement relationship of the otoconia, and
      possible otoconial deflections that are not co-linear with the direction of the
      input force (cross-talk). The free parameters of our model relate entirely to the
      mechanical otolith model. They were determined by fitting the integrated
      mechanical/perceptual model to subjective indications of the vertical obtained
      during pitch and roll body tilts in 1g and 2g force backgrounds and during
      recumbent yaw tilts in 1g. The complete data set was fit with very little
      residual error. A novel prediction of the model is that background force
      magnitude either lower or higher than 1g will not affect subjective vertical
      judgments during recumbent yaw tilt. These predictions have been confirmed in
      recent parabolic flight experiments.

PMID- 16628401
TI  - Localization of the subjective vertical during roll, pitch, and recumbent yaw
      body tilt.
AB  - Localization of the subjective vertical during body tilt in pitch and in roll has
      been extensively studied because of the relevance of these axes for aviation and
      control of posture. Studies of yaw orientation relative to gravity are lacking.
      Our goal was to perform the first thorough evaluation of static orientation in
      recumbent yaw and to collect as efficiently as possible roll and pitch
      orientation data which would be consistent with the literature, using the same
      technique as our yaw tests. This would create the first comprehensive, coherent
      data set for all three axes suitable for quantitative tri-dimensional modeling of
      spatial orientation. We tested localization of the vertical for subjects tilted
      in pitch (-100 degrees to +130 degrees ), in roll (-90 degrees to +90 degrees ),
      and in yaw while recumbent (-80 degrees to +80 degrees ). We had subjects point a
      gravity-neutral probe to the gravitational vertical (haptically indicated
      vertical) and report verbally their perceived tilt. Subjects underestimated their
      body tilts in recumbent yaw and pitch and overestimated their tilts in roll. The
      haptic settings for pitch and roll were consistent with data in the literature
      obtained with haptic and visual indications. Our data constitute the first tri
      dimensional assessment of the subjective vertical using a common measurement
      procedure and provide the basis for the tri-axial modeling of vestibular function
      presented in the companion paper.

PMID- 16628404
TI  - Molecularly imprinted polymers applied to the clean-up of zearalenone and alpha
      zearalenol from cereal and swine feed sample extracts.
AB  - A molecularly imprinted polymer prepared using 1-allylpiperazine (1-ALPP) as the
      functional monomer, trimethyltrimethacrylate (TRIM) as the crosslinker and the
      zearalenone (ZON)-mimicking template cyclododecanyl-2,4-dihydroxybenzoate (CDHB)
      has been applied to the clean-up and preconcentration of this mycotoxin
      (zearalenone) and a related metabolite, alpha-zearalenol (alpha-ZOL), from cereal
      and swine feed sample extracts. The extraction of ZON and alpha-ZOL from the food
      samples was accomplished using pressurized liquid extraction (PLE) with MeOH/ACN
      (50:50, v/v) as the extraction solvent, at 50 degrees C and 1500 psi. The
      extracted samples were cleaned up and preconcentrated through the MIP cartridge
      and analyzed using HPLC with fluorescence detection (lambda (exc)=271/ lambda
      (em)=452 nm). The stationary phase was a polar endcapped C18 column, and
      ACN/MeOH/water 10/55/35 (v/v/v, 15 mM ammonium acetate) at a flow rate of 1.0 mL
      min(-1) was used as the mobile phase. The method was applied to the analysis of
      ZON and alpha-ZOL in wheat, corn, barley, rye, rice and swine feed samples
      fortified with 50, 100 and 400 ng g(-1) of both mycotoxins, and it gave
      recoveries of between 85 and 97% (RSD 2.1-6.7%, n=3) and 87-97% (RSD 2.3-5.6%,
      n=3) for alpha-ZOL and ZON, respectively. The method was validated using a corn
      reference material for ZON.

PMID- 16628405
TI  - DOAS tomography for the localisation and quantification of anthropogenic air
      pollution.

PMID- 16628406
TI  - Analysis of oligomers in atmospheric aerosol particles--analytical challenges.

PMID- 16628409
TI  - Decrease in rat internal anal pressure with the use of a topical ointment
      containing a killed E. coli culture suspension.
AB  - OBJECTIVES: The present study aimed to clarify the mechanisms of a topical
      ointment containing an Escherichia coli culture suspension and hydrocortisone
      (Posterisan forte, BCS+HC) in lowering internal anal pressure in conscious rats.
      MATERIALS AND METHODS: Internal anal pressure was measured using a water-filled
      balloon system for consecutive 10-min periods. The changes in pressure were
      evaluated by the number of peaks above 20 mmH2O between 1 and 8 min of recording.
      RESULTS: Topical intra-anal application of BCS+HC ointment (160 mg/kg)
      significantly decreased the internal anal pressure at 3 h after the application.
      Thereafter, this effect reached a maximum decrease at 4 h and lasted until 6 h.
      BCS+HC ointment (40, 80, and 160 mg/kg) lowered the internal anal pressure at 4-5
      h in a dose-dependent manner. The maximum decrease ratios of the ointment and
      corresponding hydrocortisone-free ointment (Posterisan, BCS) were 32.6+/-12.7 and
      25.7+/-9.0%, respectively, revealing significant pressure-lowering effects
      compared with a placebo (P<0.05). In contrast, the same ointment containing
      hydrocortisone alone and other ointments containing steroids or local anesthetics
      had no effects. DISCUSSION: Treatment with 1 mg/kg NG-nitro-L-arginine methyl
      ester HCl (L-NAME), a non-selective nitric oxide synthase inhibitor,
      significantly suppressed the effect of BCS+HC ointment (160 mg/kg) in lowering
      the internal anal pressure. Furthermore, BCS+HC ointment (160 mg/kg)
      significantly lowered capsaicin-induced high internal anal pressure compared to a
      placebo. CONCLUSION: These findings suggest that BCS+HC and BCS ointments
      containing an E. coli culture suspension significantly lowered the internal anal
      pressure due to endogenous nitric oxide production in conscious rats.

PMID- 16628410
TI  - Identification of neurons that express 5-hydroxytryptamine4 receptors in
      intestine.
AB  - 5-Hydroxytryptamine (5-HT) is an endogenous stimulant of intestinal propulsive
      reflexes. It exerts its effects partly through 5-HT4 receptors; 5-HT4 receptor
      agonists that are stimulants of intestinal transit are in clinical use. Both
      pharmacological and recent immunohistochemical studies indicate that 5-HT4
      receptors are present on enteric neurons but the specific neurons that express
      the receptors have not been determined. In the present work, we describe the
      characterization of an anti-5-HT4 receptor antiserum that reveals
      immunoreactivity for enteric neurons and other cell types in the gastrointestinal
      tract. With this antiserum, 5-HT4 receptor immunoreactivity has been found in the
      muscularis mucosae of the rat oesophagus, a standard assay tissue for 5-HT4
      receptors. It is also present in the muscularis mucosae of the guinea-pig and
      mouse oesophagus. In guinea-pig small intestine and rat and mouse colon, 5-HT4
      receptor immunoreactivity occurs in subpopulations of enteric neurons, including
      prominent large neurons. Double-staining has shown that these large neurons in
      the guinea-pig small intestine are also immunoreactive for two markers of
      intrinsic primary afferent neurons, cytoplasmic NeuN and calbindin. Some muscle
      motor neurons in the myenteric ganglia are immunoreactive for this receptor,
      whereas it is rarely expressed by secretomotor neurons. Immunoreactivity also
      occurs in the interstitial cells of Cajal but is faint in the external muscle.
      Expression of the protein and mRNA has been confirmed in extracts containing
      enteric neurons. The observations suggest that one site of action of 5-HT4
      receptor agonists is the intrinsic primary afferent neurons.

PMID- 16628411
TI  - Orcokinin immunoreactivity in the accessory medulla of the cockroach Leucophaea
      maderae.
AB  - The accessory medulla is the master circadian clock in the brain of the cockroach
      Leucophaea maderae and controls circadian locomotor activity. Previous studies
      have demonstrated that a variety of neuropeptides are prominent neuromediators in
      this brain area. Recently, members of the orcokinin family of crustacean
      neuropeptides have been identified in several insect species and shown to be
      widely distributed in the brain, including the accessory medulla. To investigate
      the possible involvement of orcokinins in circadian clock function, we have
      analyzed the distribution of orcokinin immunostaining in the accessory medulla of
      L. maderae in detail. The accessory medulla is densely innervated by
      approximately 30 orcokinin-immunoreactive neurons with cell bodies distributed in
      five of six established cell groups in the accessory medulla. Immunostaining is
      particularly prominent in three ventromedian neurons. These neurons have
      processes in a median layer of the medulla and in the internodular neuropil of
      the accessory medulla and send axonal fibers via the posterior optic commissure
      to their contralateral counterparts. Double-labeling experiments have revealed
      the colocalization of orcokinin immunostaining with immunoreactivity for pigment
      dispersing hormone, FMRFamide, Mas-allatotropin, and gamma-aminobutyric acid in
      two cell groups of the accessory medulla, but not in the ventromedian neurons or
      in the anterior and posterior optic commissure. Immunostaining in the
      ventromedian neurons suggests that orcokinin-related peptides play a role in the
      heterolateral transmission of photic input to the pacemaker and/or in the
      coupling of the bilateral pacemakers of the cockroach.

PMID- 16628413
TI  - Thyroid transcription factor 1 (TTF-1) and p63 expression in two primary thyroid
      papillary carcinomas of branchial cleft cysts.
AB  - Malignant lateral cervical cysts can be related to metastatic tumors or rarely to
      primary thyroid carcinoma arising in branchial cleft cysts. This study evaluates
      the expression of thyroid-associated transcription factor-1 (TTF-1) and p63 in
      three branchial cleft cysts and in two primary thyroid papillary carcinoma of
      branchial cleft cysts. TTF-1 was negative in the nuclei of the lining epithelia
      of branchial cleft cysts, but positive in the adjacent normal thyroid tissue,
      while TTF-1 was positive in the nuclei of the lining epithelia and in the nuclei
      of the papillae and follicles in branchial cleft cysts with ectopic thyroid
      carcinoma. P63 was positive in the nuclei of the lining epithelia of branchial
      cleft cysts, but negative in the adjacent normal thyroid tissue. Papillary
      thyroid carcinoma of branchial cleft cysts displayed p63-positive foci. In
      conclusion, our results demonstrate that TTF-1 cannot distinguish between primary
      and metastatic tumors of branchial cleft cysts. The detection of p63 in papillary
      thyroid carcinomas of branchial cleft cysts could suggest that p63 contributes to
      the onset of this tumor. It is really important to evaluate if the case has a
      metastatic derivation or represents papillary thyroid carcinoma arising in
      ectopic thyroid tissue in a branchial cleft cyst.

PMID- 16628414
TI  - Evaluation of the prognostic significance of androgen receptor expression in
      metastatic breast cancer.
AB  - The purpose of this study was to investigate the influence of androgen receptor
      (AR) expression in tumour tissue on survival of patients with metastatic breast
      cancer. Tumour specimens from 232 patients with metastatic breast cancer were
      examined for presence of AR by immunohistochemistry. According to the extent of
      immunostaining, AR expression was classified as score 0, 1+, 2+, or 3+. AR
      positivity was observed in 164 (70.7%) tumours. The median survival after disease
      recurrence (SAR) of patients with AR-expressing tumours was significantly longer
      compared to that of patients with AR-negative tumours (21.89 months, 95% CI 17.23
      26.55 vs 11.99 months, 95% CI 9.36-14.62; log-rank test 0.0282). In addition,
      patients with AR score 3+ had a significantly longer disease-free survival (DFS)
      compared to patients with AR score 0, 1+, and 2+, (24.67 months, 95% CI 13.72
      35.62 vs 16.36 months, 95% CI 13.18-19.54, log-rank test 0.0043). Multivariate
      Cox analyses showed no statistically significant influence of AR expression on
      DFS or SAR. In conclusion, SAR is significantly longer in patients with AR
      expressing breast carcinoma. However, AR expression is not an independent
      prognostic factor for SAR in metastatic breast cancer.

PMID- 16628415
TI  - Predicting diet, trophic level and palaeoecology from bone stable isotope
      analysis: a comparative study of five red deer populations.
AB  - C and N stable isotope ratios of red deer (Cervus elaphus) bone collagen (154
      individuals) from five modern populations occupying geographically different
      habitats are reported. No significant difference was observed between deer
      occupying forested and non-forested environments subject to similar climatic
      conditions suggesting a simple "canopy effect" is not observed. Mean population
      delta13C is negatively correlated with temperature whereas mean population
      delta15N is positively correlated with temperature. A weak but significant
      positive correlation was observed between deer age and collagen delta13C values
      from the Isle of Rum population (Scotland). The amount of intra-population
      isotope variability is not consistent among populations; thus significant numbers
      of individuals from each species are required for modern food web studies, for
      palaeodietary baseline data, and for palaeoecological studies.

PMID- 16628416
TI  - Improved systemic safety and risk-benefit ratio of topical 0.1% timolol hydrogel
      compared with 0.5% timolol aqueous solution in the treatment of glaucoma.
AB  - PURPOSE: The purpose of the study was to compare the systemic safety and risk
      benefit ratio of 0.1% timolol hydrogel and 0.5% aqueous timolol eye drops in the
      treatment of glaucoma. METHODS: An 8-week randomised, double-blind, cross-over,
      multicentre study. A total of 25 patients with primary open-angle glaucoma,
      exfoliation glaucoma, or ocular hypertension was enrolled. After completing a
      wash-out period, patients were randomly chosen to receive either 0.1% timolol
      hydrogel once daily or 0.5% aqueous timolol eye drops twice daily. Intraocular
      pressure and heart rate during rest and exercise, head-up tilt test results,
      spirometry readings, and plasma concentrations of timolol were recorded. The risk
      benefit ratio was determined by calculating the ratio between several heart rate
      endpoints and the change in intraocular pressure (IOP). RESULTS: The mean drug
      induced change in the peak heart rate during exercise was -13.5 beats/min (SD
      7.6) in the 0.5% aqueous timolol group and -5.1 beats/min (SD 6.7) in the 0.1%
      timolol hydrogel group (P<0.001; 95% CI 4.06-12.18). There was no significant
      difference in the IOP-reducing efficacy between these compounds. The risk-benefit
      ratio was significantly improved when 0.1% timolol hydrogel was used, compared
      with 0.5% aqueous timolol in the exercise test. In the head-up tilt test the risk
      benefit ratio was significantly improved at rest (P<0.05), at 1 min (P<0.05) and
      at 5 min (P<0.001) after patients had received 0.1% timolol hydrogel. There were,
      however, no differences in spirometry readings. After patients had been treated
      with 0.1% timolol hydrogel, plasma concentrations of timolol were 1/6 (at peak)
      and 1/50 (at trough) of those of 0.5% aqueous timolol. CONCLUSIONS: Drug-induced
      changes in the peak heart rate, and head-up tilt test results as well as plasma
      concentrations of timolol, were significantly more pronounced after treatment
      with 0.5% aqueous timolol than with 0.1% timolol hydrogel. Because of the
      statistically similar IOP-reducing efficacy of these formulations the risk
      benefit ratio was significantly improved when patients used 0.1% timolol hydrogel
      instead of 0.5% aqueous timolol.

PMID- 16628417
TI  - Quantification of retinal nerve fiber layer thickness reduction associated with a
      relative afferent pupillary defect.
AB  - BACKGROUND: A relative afferent pupillary defect (RAPD) is known to develop only
      when more than 25% of retinal ganglion cells are ablated in monkeys' eyes.
      However, there was no prior study to estimate biometrically the degree of retinal
      nerve fiber layer (RNFL) thickness reduction leading to the development of RAPD
      in live human eyes. The purpose of this study was to examine the correlation
      between the amount of RNFL thickness reduction and the depth of a clinically
      detectable RAPD in patients with unilateral optic atrophy. METHODS: Enrolled were
      20 patients with optic atrophy of various etiologies. We quantified RAPD by
      performing the swinging flashlight test with log-scaled neutral density filters
      placed over the unaffected eye. Average RNFL thickness was measured by OCT3000
      with the average RNFL thickness program. Linear regression analysis was used in
      assessing the relationship between RAPD and the ratio of affected to unaffected
      average RNFL thickness. RESULTS: The mean of average RNFL thickness was 95.6+/
      17.3 microm in the unaffected eyes and 50.7+/-19.3 microm in the affected eyes
      (P<0.001). Regression analysis between RAPD and the ratio of affected to
      unaffected average RNFL thickness revealed a correlation coefficient R2=0.48
      (P=0.0007). The regression line intersected the y-axis at 0.77. CONCLUSIONS: RAPD
      was not clinically detected until at least approximately 25% of the retinal nerve
      fibers were lost when compared with the unaffected eyes. Substantial retinal
      ganglion cell damage is required for the development of RAPD.

PMID- 16628418
TI  - Estimation of visual outcome without treatment in patients with subfoveal
      choroidal neovascularization in pathologic myopia.
AB  - OBJECTIVE: To clarify prognostic factors of long-term visual outcome without
      treatment in patients with myopic choroidal neovascularization (CNV) and estimate
      a regression equation to predict visual acuity at 5 years after CNV onset.
      METHODS: Fifty-four eyes of 54 consecutive patients with high myopia and
      subfoveal CNV who did not receive treatment were identified using clinical
      records from 1988 to 2004. Photodynamic therapy not approved for myopic CNV in
      Japan during this period. The association of best-corrected visual acuity (BCVA)
      at 5 years after CNV onset with patient age, refractive error, axial length,
      initial BCVA, myopic retinopathy grade, duration of persistent hemorrhage, CNV
      size at onset, and size of hemorrhage around the CNV was analyzed using
      Spearman's correlation and multiple linear regression analysis. RESULTS: BCVA at
      5 years after onset was significantly associated with patient age, CNV size, and
      initial BCVA (P<0.05, Spearman's correlation). The regression equation estimating
      BCVA at 5 years after CNV onset was based on age and initial BCVA (R2=0.43). When
      subjects were divided into groups according to age (<40 and >or=40 years), CNV
      size, axial length and duration of persistent hemorrhage influenced BCVA at 5
      years in patients under 40 years; while only initial BCVA was an influence in
      those at least 40 years old. CONCLUSIONS: We developed a linear predictive model
      to estimate BCVA at 5 years after onset of myopic CNV without treatment based on
      the identified prognostic factors. This information might be important for
      managing patients with myopic CNV.

PMID- 16628419
TI  - Clinical characteristics and surgical outcomes of pediatric cataract in Taiwan.
AB  - PURPOSE: To report treatment of pediatric patients with cataract, and evaluate
      the efficiency of different surgical interventions. METHOD: This study comprised
      a consecutive series of pediatric patients with congenital or developing cataract
      who received surgery between 1993 and 2002 at Chang Gung Memorial Hospital in
      Taiwan. Patients' demographics, cataract type, presenting symptoms, surgical
      intervention, postoperative visual acuity, and follow-up refractive changes were
      recorded. RESULTS: Three hundred and ninety-nine eyes of 246 children were
      included; unilateral cataract was present 21.8% of the eyes. The age at surgery
      was ranged from 1 to 157 months. Eyes were grouped by surgical interventions
      performed: Group 1 included 98 eyes that had lensectomy. Group 2 included 89 eyes
      that had lensectomy and secondary intraocular lens implantation. Group 3 included
      212 eyes that had lensectomy with primary intraocular implantation. The mean
      follow up time was 41.3 months. Finally, 23.1% group 1 patients, 42.1% group 2
      patients, and 63.4% group 3 patients achieved visual acuity better than 20/60
      (P=0.000). Upon analysis with multifactor regression, age at onset (P=0.011) was
      the only significant factor related to visual outcome. Complications such as
      after cataract and glaucoma occurred in 21.6% and 5.8% of all patients,
      respectively. CONCLUSIONS: Intraocular lens implantation for children with
      congenital or developing cataract is an effective treatment for visual
      rehabilitation, even for those patients age 2 years and younger.

PMID- 16628420
TI  - Effects of subretinal implant materials on the viability, apoptosis and barrier
      function of cultured RPE cells.
AB  - BACKGROUND: Subretinal microphotodiode array (MPDA) is a type of visual
      prosthesis used for the implantation in the subretinal space of patients with
      progressive photoreceptor cell loss. The present study aimed to evaluate the
      effect of materials for MPDA on the viability, apoptosis and barrier function of
      cultured pig retinal pigment epithelium (RPE) cells. METHODS: Primary culture of
      pig RPE cells was performed and 24 pig eyes were used to start RPE culture. The
      third passage of the cultures was plated on different materials for MPDA and
      MPDAs. The tetrazolium dye-reduction assay (MTT) was used to determine RPE cell
      viability. Flow cytometry was measured to indicate the apoptosis rates of RPE
      cells on different materials. RPE cells were also cultured on microporous
      filters, and the transepithelial resistance and permeability of the experimental
      molecule were measured to determine the barrier function. RESULTS: The data from
      all the methods indicated no significant difference between the materials groups
      and the control group, and the materials tested showed good biocompatibility.
      CONCLUSIONS: The materials for MPDA used in the present study had no direct
      toxicity to the RPE cells and did not release harmful soluble factors that
      affected the barrier function of RPE in vitro.

PMID- 16628421
TI  - Catastrophic acute retinal necrosis syndrome associated with diffuse orbital
      cellulitis: a case report.
AB  - BACKGROUND: To report a case of severe acute retinal necrosis syndrome (ARN)
      associated with initial features of orbital cellulitis. METHODS: A 49-year-old
      immunocompetent woman presented with unilateral painful orbital inflammation
      associated with deep visual loss due to ARN. Polymerase chain reaction (PCR) for
      detection of viral DNA was applied to ocular fluids. Immunohistochemistry for
      detection of viral antigens and histopathologic studies were performed on orbital
      biopsy specimens. RESULTS: HSV-2 DNA was detected by PCR in ocular fluids.
      Orbital biopsy disclosed non-specific inflammation without viral replication.
      Orbital inflammation resolved rapidly after the initiation of antiviral drugs,
      whereas intraocular inflammation worsened. Final ophthalmic examination disclosed
      no light perception due to optic atrophy. CONCLUSION: ARN and cellulitis may be
      associated. Consequently, ARN should be investigated in all patients with orbital
      inflammation, in order to initiate immediately an appropriate antiviral strategy.

PMID- 16628422
TI  - Recession-resection combined with intraoperative botulinum toxin A
      chemodenervation for exotropia following subtotal ruptured of medial rectus
      muscle.
AB  - BACKGROUND: Ruptured extraocular muscle loses its function and shows severe
      restriction of eye movement even after muscle-to-muscle anastomosis or muscle
      transposition surgery. We present the case of a patient who developed a large
      exotropia after near-total rupture of the medial rectus muscle following a
      blowout fracture. METHODS: Case report. RESULTS: A 12-year-old girl presented at
      our clinic with 45 prism diopters' exotropia after a blunt trauma. A forced
      duction test was unrestricted, and orbital computed tomography showed a medial
      orbital wall fracture and an impinged medial rectus muscle. Upon surgical
      exploration, an almost totally ruptured medial rectus muscle was found. The
      median margin of the ruptured muscle was 6.0 mm from its insertion, and the
      distal end that we could examine was 15.0 mm from the limbus. Recession-resection
      surgery combined with intraoperative botulinum toxin A chemodenervation to the
      ipsilateral lateral rectus muscle achieved a good primary alignment and binocular
      single visual field, even at a 9-month follow-up. CONCLUSIONS: Recession
      resection surgery augmented by intraoperative botulinum toxin A chemodenervation
      to the ipsilateral rectus muscle appears to be highly effective in the treatment
      of a large exotropia produced by subtotal rectus muscle rupture following orbital
      wall fracture, with a lower risk of anterior segment ischemia.

PMID- 16628423
TI  - Cerebral air embolism during contrast-enhanced CT.

PMID- 16628426
TI  - Traumatic manubriosternal dislocation.
AB  - Manubriosternal dislocation is an extremely rare occurrence, especially as the
      result of an indirect compression injury. Manubriosternal dislocations are
      divided into two types: In a Type I dislocation, the body of the sternum is
      displaced in a dorsal direction; in Type II dislocation, the body is displaced to
      the ventral side of the manubrium. A manubriosternal dislocation may be caused by
      direct or indirect trauma. Direct injury is generally a collision injury
      occurring in the context of a road accident. Resulting may be in either a Type I
      or Type II dislocation. Indirect trauma always leads to a Type II dislocation due
      to a flexion-compression mechanism in the region of the spine. Rheumatic
      arthritis and obvious kyphosis are predisposing factors in manubriosternal
      dislocation due to the indirect compression injury. Non-operative treatments
      after reduction, e.g. correction tape or plaster bandage, symptomatic pain
      treatment, application of ice, and several weeks without sports, are associated
      with a not inconsiderable rate of subluxations or reluxations, especially due to
      insufficient patient compliance. These disorders can lead to chronic pain,
      periarticular calcification with ankylosis, and progressive deformity. It has not
      been possible to establish an optimal, standardized operative procedure so far
      because of the small number of cases. We have achieved very good, postoperative
      long-term outcomes after plate osteosynthesis of manubriosternal dislocations in
      two patients.

PMID- 16628427
TI  - Two cannulated hip screws for femoral neck fractures: treatment of choice or
      asking for trouble?
AB  - INTRODUCTION: Undisplaced intracapsular fractures are predominantly treated with
      a minimally invasive fixation technique, whereas the standard treatment for
      displaced intracapsular fractures is still a subject of discussion. The purpose
      of this study was to identify the determinants influencing the outcome of
      intracapsular femoral neck fractures, treated with two cannulated hip screws.
      PATIENTS AND METHODS: From January 1998 through December 2002 data of all
      consecutive patients with an intracapsular femoral fracture, treated with two
      cannulated screws, were documented. Consolidation was chosen as the primary
      endpoint, mortality and a reoperation for replacement of osteosynthesis were
      defined secondary endpoints. RESULTS: One hundred and twelve patients were
      included in the study. Fifty six percent of the intracapsular fractures healed
      within 1 year. Consolidation was accomplished in 95% of the stable fractures.
      Consolidation rates were negatively influenced by unstable fractures and
      inadequate anatomical reduction. The position of the screws did not influence
      consolidation rates. Reintervention rates were related to the number of local
      complications and the fracture type. CONCLUSION: In conclusion, the results of
      this study show that in case of operative treatment, undisplaced femoral neck
      fractures can be adequately fixated by two cannulated hip screws. Unstable,
      anatomically reduced femoral neck fracture (Garden III/IV) may be treated with a
      more stable implant (e.g. DHS) to avoid redisplacement. If adequate reduction
      cannot be achieved, endoprosthetic replacement is recommended.

PMID- 16628428
TI  - The fixation strength of hydroxyapatite-coated Schanz screws and standard
      stainless steel Schanz screws in lower extremity lengthening : a comparison based
      on a new torque value index: the fixation index.
AB  - INTRODUCTION: Lengthening procedures are often complicated by loosening of pins.
      It has been reported that coating with hydroxyapatite improves fixation and
      reduces the rate of pin-track infection. MATERIALS AND METHODS: We compared 47
      hydroxyapatite-coated Schanz screws (HA screws) in 12 monolateral fixators
      mounted at the University Hospital Hamburg-Eppendorf with 45 standard stainless
      steel screws in 9 monolateral fixators mounted at the St Josefs-Hospital
      Wiesbaden by measuring the insertion and extraction torque values. The average
      implantation period was 7 months for the hydroxyapatite-coated screws and 5.4
      months for the uncoated screws. We established the quotient of the maximum
      extraction torque over insertion torque which shows the change in the fixation
      strength with respect to time, the fixation index. It eliminates the influence of
      the varying pin-bone contact. RESULTS: There was no significant difference in the
      rate of infection. In the Schanz screws without signs of infection the index was
      1.92 for the HA screws and 0.76 for the stainless steel screws (P = 0.0002)
      giving evidence of the improvement of the fixation by the coating. CONCLUSION: HA
      coating resulted in improved fixation of Schanz screws in bone and may be useful
      in prolonged external fixation of the lower leg. The fixation index proved to be
      a simple tool for the evaluation of the fixation strength of Schanz screws.

PMID- 16628429
TI  - Total hip arthroplasty of dysplastic hip after previous Chiari pelvic osteotomy.
AB  - INTRODUCTION: Many reports have suggested that Chiari pelvic osteotomy would
      improve the results of acetabular component placement and fixation in subsequent
      total hip arthroplasty. However, little is known concerning the biomechanical,
      radiological, and clinical effects of Chiari pelvic osteotomy on subsequent total
      hip arthroplasty. MATERIALS AND METHODS: Ten total hip arthroplasties for
      developmental dysplasia of the hip after previous Chiari pelvic osteotomy (Chiari
      group) were compared with 20 total hip arthroplasties for developmental dysplasia
      of the hip without previous surgery (control group). Preoperative patient
      demographic data and operative technique were well matched between the groups.
      The mean duration of follow-up was 3.0 years. Biomechanical, radiological, and
      clinical evaluations were performed. RESULTS: No acetabular or femoral components
      exhibited loosening. All patients had good or excellent clinical score according
      to the Merle d'Aubigne-Postel rating system at the most recent follow-up.
      Abductor force and joint force were smaller in the Chiari group, although long
      operative time, more blood loss, and verticalization of joint force were noted in
      this group. CONCLUSION: This limited study suggested that Chiari pelvic osteotomy
      changed the biomechanical features of the hip joint, and that this alteration
      might have compromised subsequent total hip arthroplasty.

PMID- 16628430
TI  - Characteristics and outcome of infections associated with tumor endoprostheses.
AB  - INTRODUCTION: Infection associated with prosthesis used after tumor resection is
      a common and serious complication. The purpose of the current retrospective study
      was to describe the course of infection in patients with a tumor endoprosthesis
      and the determination of risk factors associated with failed limb salvage.
      MATERIAL AND METHODS: 30 patients with an infection associated with a tumor
      endoprosthesis were investigated with regard to treatment strategies, number and
      type of revision operations, duration of hospital stay, determination of risk
      factors associated with failed limb salvage and final outcome. RESULTS: Limb
      salvage related to the complication infection was achieved in 19 patients
      (63.3%). Two-stage reimplantation of an endoprosthesis was successful in 14
      patients but subsequently failed in one patient. Out of 11 patients where limb
      salvage failed, an amputation was performed in 6 patients, a rotationplasty in 4,
      and stump lengthening procedure in 1 patient. A poor soft tissue condition was a
      significant (P<0.05) risk factor for failed limb salvage. No patient receiving
      chemotherapy with a poor soft tissue condition had limb salvage surgery. The mean
      number of revision operations per patients was 2.6. The mean duration of hospital
      stay was 68 days. CONCLUSION: Infection associated with prosthesis is a serious
      complication and is involved with long hospitalization. Limb salvage failed
      mostly in the case of a poor soft tissue condition. In these cases repeated
      revision surgery should be avoided and ablative surgery recommended at an early
      stage. Rotationplasty is an alternative to amputation in the case of an infection
      of the proximal or distal part of the femur.

PMID- 16628432
TI  - Radiocesium in mushrooms from selected locations in the Czech Republic and the
      Slovak Republic.
AB  - In this paper, activity concentrations of radiocesium in mushrooms from various
      locations in the Czech Republic and the Slovak Republic in the years 2000-2004
      are presented. Summary reports of Czech regulatory bodies have judged the average
      activity concentrations in mushrooms to be remarkably below the maximum
      permissible level of contamination. However, there are certain regions where
      radiocesium activities have approached the maximum permissible level for
      contamination of basic foodstuff. For example, the highest activity concentration
      of (137)Cs measured by gamma-spectrometry was 2,263 Bq kg(-1) (on a dry mass
      basis), in Xerocomus badius from Stare Ransko (a locality in the Czech-Moravian
      Highlands, Czech Republic). The highest activity concentration of (137)Cs
      measured in Slovakia was 966 Bq kg(-1) (on a dry mass basis), for Suillus luteus
      from Senica. For comparison, the corresponding activity concentration in a sample
      taken within the 30 km zone around Chernobyl was measured to be 6,000 Bq kg(-1)
      (on a dry mass basis). Our results have also demonstrated remarkably lower
      activity concentrations of (137)Cs in Slovakia compared to those in the Czech
      Republic.

PMID- 16628437
TI  - [Conventional x-ray after shoulder prosthesis].
AB  - Three types of shoulder prostheses are commonly used to cover the different
      indications of shoulder joint replacements: classical modular, inverse and cup.
      The modular prosthesis can replace the glenoid as well as the humeral head
      components. Exact visualization of the interface between the glenoid component
      and bone (or cement-bone interface) is necessary to detect osteolysis, which is
      relatively common. Therefore, it is mandatory to make true AP and axial
      projections. When describing the humeral component, the interface between bone
      and implant must again be considered. Additionally, the position of the humeral
      head in relation to the glenoid has to be noted. The glenoid component is usually
      fixed by screws to the bone and an osteolysis is often present at the inferior
      pole of the glenoid component due to prosthesis bone notching. If the implants
      are modular devices (classic modular prosthesis, inverse shoulder prosthesis)
      there is the possibility of dissociation of components and any suspicion of this
      should be reported. In case of reporting the conventional x-ray of cup
      prosthesis, the bone implant interface should be mentioned. Again the position of
      the humeral head to the glenoid requires attention. In all types of prostheses,
      dislocation of the glenohumeral joint is obvious and has to be addressed in the
      medical report.

PMID- 16628438
TI  - Therapy monitoring using dynamic MRI: analysis of lung motion and intrathoracic
      tumor mobility before and after radiotherapy.
AB  - A frequent side effect after radiotherapy of lung tumors is a decrease of
      pulmonary function accompanied by dyspnea due to developing lung fibrosis. The
      aim of this study was to monitor lung motion as a correlate of pulmonary function
      and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic
      MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were
      examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and
      T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal
      (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital
      capacity (VC) was measured and correlated using spirometry. Before RT, the
      maximum CC motion of the tumor-bearing hemithorax was 5.2 +/- 0.9 cm if the tumor
      was located in the lower LR (middle LR: 5.5 +/- 0.8 cm; upper LR: 6.0 +/- 0.6
      cm). After RT, lung motion was significantly reduced in the lower LR (P < 0.05).
      Before RT, the maximum CC tumor mobility was significantly higher in tumors of
      the lower LR 2.5 +/- 0.6 vs. 2.0 +/- 0.3 cm (middle LR; P < 0.05) vs. 0.7 +/- 0.2
      cm (upper LR; P < 0.01). After RT, tumor mobility was significantly reduced in
      the lower LR (P < 0.01) and in T2 tumor patients (P < 0.05). VC showed no
      significant changes. dMRI is capable of monitoring changes in lung motion that
      were not suspected from spirometry. This might make the treatment of side effects
      possible at a very early stage. Changes of lung motion and tumor mobility are
      highly dependent on the tumor localization and tumor diameter.

PMID- 16628439
TI  - The accuracy of MRI in diagnosis of suspected deep vein thrombosis: systematic
      review and meta-analysis.
AB  - Magnetic resonance imaging (MRI) may be used to diagnose deep vein thrombosis
      (DVT) in patients for whom ultrasound examination is inappropriate or unfeasible.
      We undertook a systematic review of the literature and meta-analysis to estimate
      the diagnostic accuracy of MRI for DVT. We searched databases of medical
      literature and citation lists of retrieved articles. We selected studies that
      compared MRI with a reference standard in patients with suspected DVT or
      suspected pulmonary embolus, or high-risk asymptomatic patients. Data were
      analysed by random effects meta-analysis. We included 14 articles in the meta
      analysis. Most compared MRI with venography in patients with clinically suspected
      DVT. The pooled estimate of sensitivity was 91.5% (95% CI: 87.5-94.5%) and the
      pooled estimate of specificity was 94.8% (95% CI: 92.6-96.5%). Sensitivity for
      proximal DVT was higher than sensitivity for distal DVT (93.9% versus 62.1%).
      However, pooled estimates should be interpreted with caution as estimates of both
      sensitivity and specificity were subject to significant heterogeneity (P<0.001).
      Individual studies reported sensitivity ranging from zero to 100%, while
      specificity ranged from 43 to 100%. MRI has equivalent sensitivity and
      specificity to ultrasound for diagnosis of DVT, but has been evaluated in many
      fewer studies, using a variety of different techniques.

PMID- 16628441
TI  - Backstroke technique: an effective way to improve the healing of tibia fracture.
AB  - To assess the method and results of applying a backstroke technique, we treated
      43 patients with tibial shaft fracture using unreamed tibial nails (UTN). Of
      these patients, 27 suffered a closed fracture and 16 an open fracture. After the
      operation, the effect of treatment was evaluated: 42 of 43 cases were followed up
      from four to 18 months, averaging 13.6 months. The four-month and 12-month
      healing rates of open fracture were 54.6 and 80.9%, respectively, the former of
      which is significantly higher than the average rate of the AO/ASIF multicentre
      study. Our results indicate that applying a backstroke technique in treating
      tibial shaft fracture with UTN can improve the healing rate and reduce
      complications.

PMID- 16628443
TI  - Cervical pedicle screw placement: feasibility and accuracy of two new insertion
      techniques based on morphometric data.
AB  - This morphometric and experimental study was designed to assess the dimensions
      and axes of the subaxial cervical pedicles and to compare the accuracy of two
      different techniques for subaxial cervical pedicle screw (CPS) placement using
      newly designed aiming devices. Transpedicular fixation is increasingly used for
      stabilizing the subaxial cervical spine. Development of the demanding technique
      is based on morphometric studies of the pedicle anatomy. Several surgical
      techniques have been developed and evaluated with respect to their feasibility
      and accuracy. The study was carried out on six conserved human cadavers (average
      age 85 years). Axes and dimensions of the pedicles C3-C7 (60 pedicles) were
      measured using multislice computed tomography (CT) images prior to surgery. Two
      groups consisting of 3 specimens and 30 pedicles each were established according
      to the screw placement technique. For surgical technique 1 (ST1) a para-articular
      mini-laminotomy was performed. Guidance of the drill through the pedicle with a
      handheld aiming device attached onto the medial aspect of the pedicle inside the
      spinal canal. Screw hole preparation monitored by lateral fluoroscopy. In
      surgical technique 2 (ST2) a more complex aiming device was used for screw holes
      drilling. It consists of a frame with a fully adjustable radiolucent arm for
      carrying the instruments necessary for placing the screws. The arm was angled
      according to the cervical pedicle axis as determined by the preoperative CT
      scans. Drilling was monitored by lateral fluoroscopy. In either technique 3.5 mm
      screws made of carbon fiber polyetheretherketone (CF-PEEK) were inserted. The use
      of the CF-PEEK screws allowed for precise postoperative CT-assessment since this
      material does not cause artifacts. Screw placement was qualified from ideal to
      unacceptable into four grades: I = screw centered in pedicle; IIa = perforation
      of pedicle wall less than one-fourth of the screw diameter; IIb = perforation
      more than one-fourth of the screw diameter without contact to neurovascular
      structures; III = screw more than one-fourth outside the pedicle with contact to
      neurovascular structures. Fifty-six pedicle screws could be evaluated according
      to the same CT protocol that was used preoperatively. Accuracy of pedicle screw
      placement did not reveal significant differences between techniques 1 and 2. A
      tendency towards less severe misplacements (grade III) was seen in ST2 (15% in
      ST2 vs. 23% in ST1) as well as a higher rate of screw positions graded IIa (62%
      in ST2 vs. 43% in ST1). C4 and C5 were identified to be the most critical
      vertebral levels with three malpositioned screws each. Because of the variability
      of cervical pedicles preoperative CT evaluation with multiplanar reconstructions
      of the pedicle anatomy is essential for transpedicular screw placement in the
      cervical spine. Cadaver studies remain mandatory to develop safer and technically
      less demanding procedures. A similar study is projected to further develop the
      technique of CPS fixation with regard to safety and clinical practicability.

PMID- 16628446
TI  - Proteolytic systems of lactic acid bacteria.
AB  - Lactic acid bacteria (LAB) have a very long history of use in the manufacturing
      processes of fermented foods and a great deal of effort was made to investigate
      and manipulate the role of LAB in these processes. Today, the diverse group of
      LAB includes species that are among the best-studied microorganisms and
      proteolysis is one of the particular physiological traits of LAB of which
      detailed knowledge was obtained. The proteolytic system involved in casein
      utilization provides cells with essential amino acids during growth in milk and
      is also of industrial importance due to its contribution to the development of
      the organoleptic properties of fermented milk products. For the most extensively
      studied LAB, Lactococcus lactis, a model for casein proteolysis, transport,
      peptidolysis, and regulation thereof is now established. In addition to nutrient
      processing, cellular proteolysis plays a critical role in polypeptide quality
      control and in many regulatory circuits by keeping basal levels of regulatory
      proteins low and removing them when they are no longer needed. As part of the
      industrial processes, LAB are challenged by various stress conditions that are
      likely to affect metabolic activities, including proteolysis. While environmental
      stress responses of LAB have received increasing interest in recent years, our
      current knowledge on stress-related proteolysis in LAB is almost exclusively
      based on studies on L. lactis. This review provides the current status in the
      research of proteolytic systems of LAB with industrial relevance.

PMID- 16628447
TI  - Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and
      environmental significance.
AB  - Heme-thiolate haloperoxidases are undoubtedly the most versatile biocatalysts of
      the hemeprotein family and share catalytic properties with at least three further
      classes of heme-containing oxidoreductases, namely, classic plant and fungal
      peroxidases, cytochrome P450 monooxygenases, and catalases. For a long time, only
      one enzyme of this type--the chloroperoxidase (CPO) of the ascomycete
      Caldariomyces fumago--has been known. The enzyme is commercially available as a
      fine chemical and catalyzes the unspecific chlorination, bromination, and
      iodation (but no fluorination) of a variety of electrophilic organic substrates
      via hypohalous acid as actual halogenating agent. In the absence of halide, CPO
      resembles cytochrome P450s and epoxidizes and hydroxylates activated substrates
      such as organic sulfides and olefins; aromatic rings, however, are not
      susceptible to CPO-catalyzed oxygen-transfer. Recently, a second fungal
      haloperoxidase of the heme-thiolate type has been discovered in the agaric
      mushroom Agrocybe aegerita. The UV-Vis adsorption spectrum of the isolated enzyme
      shows little similarity to that of CPO but is almost identical to a resting-state
      P450. The Agrocybe aegerita peroxidase (AaP) has strong brominating as well as
      weak chlorinating and iodating activities, and catalyzes both benzylic and
      aromatic hydroxylations (e.g., of toluene and naphthalene). AaP and related
      fungal peroxidases could become promising biocatalysts in biotechnological
      applications because they seemingly fill the gap between CPO and P450 enzymes and
      act as "self-sufficient" peroxygenases. From the environmental point of view, the
      existence of a halogenating mushroom enzyme is interesting because it could be
      linked to the multitude of halogenated compounds known from these organisms.

PMID- 16628448
TI  - Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of sugars,
      alcohols, and organic acids with transcriptional microarrays.
AB  - Microorganisms respond to environmental changes by reprogramming their metabolism
      primarily through altered patterns of gene expression. DNA microarrays provide a
      tool for exploiting microorganisms as living sensors of their environment. The
      potential of DNA microarrays to reflect availability of nutrient components
      during fermentations on complex media was examined by monitoring global gene
      expression throughout batch cultivation of Escherichia coli MG1655 on Luria
      Bertani (LB) medium. Gene expression profiles group into pathways that clearly
      demonstrate the metabolic changes occurring in the course of fermentation.
      Functional analysis of the gene expression related to metabolism of sugars,
      alcohols, and organic acids revealed that E. coli growing on LB medium switches
      from a sequential mode of substrate utilization to the simultaneous one in the
      course of the growth. Maltose and maltodextrins are the first of these substrates
      to support growth. Utilization of these nutrients associated with the highest
      growth rate of the culture was followed by simultaneous induction of enzymes
      involved in assimilation of a large group of other carbon sources including D
      mannose, melibiose, D-galactose, L-fucose, L-rhamnose, D-mannitol, amino sugars,
      trehalose, L-arabinose, glycerol, and lactate. Availability of these nutrients to
      the cells was monitored by induction of corresponding transport and/or catabolic
      systems specific for each of the compounds.

PMID- 16628449
TI  - Influence of the mechanical properties of the muscle-tendon unit on force
      generation in runners with different running economy.
AB  - In earlier studies, we found more economical runners having a more compliant
      quadriceps femoris (QF) tendon at low force levels, and a higher contractile
      strength and stiffness at the triceps surae (TS). To better understand how these
      differences influence force generation economy and energy recovery, we simulated
      contractions using a Hill-type muscle model and the previously determined muscle
      properties as input parameters. For eight different activation levels, we
      simulated isovelocity concentric contractions preceded by an isovelocity stretch.
      The length changes and contraction velocities imposed to the muscle-tendon units
      (MTU) corresponded to those happening whilst running. The main results of the
      simulations were: (a) a more compliant tendon at low force levels (QF) led to an
      advantage in force-generation due to a decrease in shortening velocity of the CE,
      (b) a higher contractile strength and higher stiffness at the TS led to a
      disadvantage in force-generation at high activation levels and to an advantage at
      low activation levels. In addition at the high economy runners both MTUs showed
      an advantageous energy release during shortening, which at the QF was mainly due
      to a higher elongation of the SEE and at the TS mainly to the higher contractile
      strength. Especially at low activation levels both MTUs showed an advantageous
      force generation per activation and a higher energy release as compared to the
      low economy runners.

PMID- 16628450
TI  - Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early
      onset Alzheimer's disease in Mexican families.
AB  - The etiology of Alzheimer's disease (AD) is complex. To date, molecular genetic
      studies in several families affected with AD have identified three genes
      associated with highly penetrant early-onset AD: Presenilin 1 (PSEN1), Presenilin
      2 (PSEN2) and beta-amyloid precursor protein (APP); and one gene (apolipoprotein
      E) associated with late-onset AD. Molecular analysis of the PSEN1 gene was
      performed by direct sequencing of genomic DNA. The possible founder effect was
      investigated analyzing two highly polymorphic microsatellite markers flanking the
      PSEN1 gene. Twelve unrelated Mexican families with early-onset AD were analyzed.
      The Ala431Glu mutation in exon 12 of PSEN1 was found in nine (75%) of these
      families, which segregated showing autosomal dominant inheritance. Because all
      families bearing the mutation are from the State of Jalisco (located in Western
      Mexico), a founder effect was hypothesized. Microsatellite haplotype analysis
      suggested a common ancestor in these nine kindreds. In conclusion, the Ala431Glu
      mutation is a prevalent cause of early-onset familial Alzheimer's disease in
      families from the State of Jalisco, Mexico. Genetic evidence supports that it is
      a founder mutation descending from a single common ancestor. These findings have
      important implications for prompt diagnosis and genetic counseling for Mexican
      patients with familial AD from Jalisco.

PMID- 16628452
TI  - Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism
      in rabbits.
AB  - Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery
      and trauma. We hypothesized that air emboli in the lung circulation might change
      expired nitric oxide (FeNO). A single intravenous infusion of air was given (100
      mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A)
      one with intact NO production, (B) one with intact NO production and where end
      tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L:
      -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control
      group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P <
      0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P <
      0.05). Parallel to the NO increase there were significant decreases in end-tidal
      CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation
      pressure. In group B, when CO(2) was supplemented after air infusion, NO was
      suppressed (P = 0.033), but was still significantly elevated compared with pre
      infusion control (P < 0.05). In group C, all animals died within 40 min of air
      infusion whereas all animals in the other groups were still alive at this time
      point. We conclude that venous air embolization increases FeNO, and that a part
      of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an
      intact NO production may be critical for the tolerance to VGE. Finally, FeNO
      might have a potential in the diagnosis and monitoring of pulmonary gas embolism.

PMID- 16628454
TI  - Temporal variation in parasite infestation of a host individual: does a parasite
      free host remain uninfested permanently?
AB  - Host individuals not infested by parasites at a given time are either permanently
      free from parasites or could be infested at other times. We studied temporal
      variation in the presence or absence of fleas (Siphonaptera) on individual
      rodents of two species (Gerbillus dasyurus and Acomys cahirinus) and questioned
      if and how an individual rodent can change its infestation status temporally.
      Change in infestation status by fleas over time was found in 45.5% of G. dasyurus
      and 35.9% of A. cahirinus. In both host species, the proportion of individuals
      that either changed or did not change their infestation status did not differ
      from the null expectation of 1:1. No difference between the proportions of
      infested at two consecutive captures and uninfested at two consecutive captures
      animals was found in A. cahirinus, whereas the proportion of G. dasyurus infested
      by fleas at two consecutive captures was significantly greater than that of
      uninfested at two consecutive captures individuals. In both host species, similar
      proportions of individuals changed their infestation status either from being
      infested to being uninfested or vice versa. Among individuals of both species
      that were initially infested by fleas, similar proportions changed and did not
      change their subsequent infestation status. The same was true for the uninfested
      at the first capture A. cahirinus. However, among initially uninfested G.
      dasyurus, the proportion of individuals that remained uninfested was
      significantly greater than that of the individuals newly infested by fleas. In A.
      cahirinus, the probability to change the infestation status did not depend on the
      initial status of an individual. In G. dasyurus, the probability of the initially
      uninfested individuals to be subsequently found still uninfested was higher than
      to be subsequently found harboring fleas, whereas initially infested individuals
      could be subsequently found either still infested or flea-free with equal
      probability.

PMID- 16628455
TI  - Humoral immune reaction of newborn calves congenitally infected with Neospora
      caninum and experimentally treated with toltrazuril.
AB  - Neospora caninum is widely recognized as one of the most important infectious
      organisms causing abortion and stillbirth in cattle. This parasite causes severe
      economical losses worldwide. Infection is mostly passed vertically from mother to
      calf during pregnancy. Under certain circumstances, an infection can lead to
      abortion, but in most cases it results in a chronically infected calf, which
      itself will represent the next endogenously infectious generation. So far, no
      reliable therapeutic or metaphylactic tool has been developed. One possibility to
      control the problem may consist of treating newborn calves that became vertically
      infected by a persistently infected mother. This may allow parasite-free
      offspring. The aim of the present study was to address the questions: (1) can
      serology be used to assess efficiency of treatment in toltrazuril-medicated
      animals? and (2) is a strategic prevention measure possible by means of producing
      N. caninum-free calves from positive cows? Calves from Neospora-seropositive cows
      and heifers were randomly split into two different medication groups: 36 calves
      were medicated with toltrazuril and 36 calves obtained a placebo. Medication (20
      mg toltrazuril per kg bw) was administered three times, every second day, within
      the 7 days post natum. Three months after medication, there was no difference in
      antibody reactivity between the two groups. At later time points (4-6 months),
      however, significant differences were found, as explained by a strong humoral
      immunity after chemotherapeutical affection of parasites, while the placebo
      treated animals only responded weakly to the persistent infection. In summary, we
      concluded that (1) serology was not an entirely appropriate tool to answer our
      initial question and (2) toltrazuril has the potential to eliminate N. caninum in
      newborn calves. As a consequence, we plan to follow up toltrazuril-medicated
      calves clinically and serologically over a longer period and investigate if they
      give birth to Neospora-free calves.

PMID- 16628456
TI  - Endocytic portals in Trypanosoma cruzi epimastigote forms.

PMID- 16628457
TI  - PCR fingerprinting of Blastocystis isolated from symptomatic and asymptomatic
      human hosts.
AB  - Genomic DNA from 16 Blastocystis hominis isolates comprising of eight
      asymptomatic isolates (A1-A8) and eight symptomatic isolates (S1-S8) was
      amplified by arbitrarily primed polymerase chain reaction (AP-PCR) using 38
      arbitrary 10-mer primers. Six primers (A10, B5, C20, D1, F6, and F10) generated
      reproducible DNA fingerprints. AP-PCR amplification revealed similar DNA
      fingerprints among all symptomatic isolates (S1-S8) with common bands at 850 bp
      using primer A10, 920 bp using primer B5, and 1.3 kbp using primer D1. Isolates
      A1, A3, A4, A5, A6, and A7 showed similar DNA banding patterns and all
      asymptomatic isolates (A1-A8) shared a major band at 1 kbp using primer B5.
      Isolates A2 and A8 showed distinct DNA banding patterns that differed from the
      remainder of the isolates. The results of the phylogenetic analyses showed that
      all symptomatic isolates (S1-S8) formed a clade with >70% similarity among the
      isolates and which were clearly separate from asymptomatic isolates A1, A3, A4,
      A5, A6, and A7. Asymptomatic isolates A2 and A8 formed two distinct and separate
      clades. AP-PCR revealed higher genetic variability within the asymptomatic
      isolates than within the symptomatic isolates. The present study suggests that AP
      PCR can be a valuable method for differentiating between isolates of B. hominis
      and our results support the hypothesis that our asymptomatic and symptomatic B.
      hominis isolates may represent two different strains/species with varying
      pathogenic potential.

PMID- 16628458
TI  - In vitro investigation of the influence of tibial slope on quadriceps extension
      force after total knee arthroplasty.
AB  - The purpose of this study was to investigate the influence of tibial base plate
      angulation on knee kinematics and kinetics during knee arthroplasty. The amount
      of quadriceps force required to extend the knee and the anteroposterior
      displacement of a mobile bearing insert as well as tibiofemoral position were
      measured during an in vitro simulation of an isokinetic knee extension cycle.
      Human knee specimens (n = 7, mean age 62, range 52-75 years, all male) were
      tested in a kinematic knee simulating machine after total knee arthroplasty (TKA)
      with a mobile bearing insert prosthesis (Interax), Stryker/Howmedica). During
      simulation, a hydraulic cylinder applied sufficient force to the quadriceps
      tendon to produce an extension moment of 31 N m about the knee. The quadriceps
      load was measured using a load cell attached to the quadriceps tendon, the
      anteroposterior displacement of the mobile bearing insert as well as the relative
      tibiofemoral position was measured using an ultrasound base motion analysis
      system (CMS 100, Zebris). Quadriceps load, insert and tibial displacement were
      first investigated with the tibial base plate implanted with a neutral tibial
      base plate orientation, and subsequently after 10 degrees posterior angulation.
      The quadriceps forces needed to produce a 31 N m knee extension moment after TKA
      with neutral slope reached levels as high as 1,391 N (SD 82 N). After applying a
      posterior slope of 10 degrees , maximum quadriceps force was measured to be up to
      1,303 N (SD 34 N, P = 0.04). The mobile bearing insert was observed to move up to
      0.1 mm (SD 4.2 mm) anteriorly relative to the tibial base plate with neutral
      tibial slope, and up to 1.0 mm (SD 4.5 mm, P = 0.47) with tibial slope. Femoral
      position relative to the tibia moved from a posterior position of 13.1 mm (SD 4.0
      mm) anteriorly up to 0.5 mm (SD 6.3 mm), and from 16.0 mm (SD 6.4 mm, P = 0.67)
      to 9.5 mm (SD 9.9 mm, P = 0.33) with a 10 degrees tibial slope. Posterior slope
      of the tibial base plate resulted in a more physiologic insert movement with a
      more posterior position of the femur and reduced quadriceps force especially in
      knee flexion angles above 60 degrees compared to TKA with a neutral slope of the
      tibial base plate. Thus, the data suggest that the quadriceps lever arm was
      improved, which might have positive effect in mobilization of patients after TKA.

PMID- 16628459
TI  - Multicenter-study of operative treatment of intraligamentous tears of the
      anterior cruciate ligament in children and adolescents: comparison of four
      different techniques.
AB  - Tears of the anterior cruciate ligament in skeletally immature patients were
      operated with four different methods and their outcome compared to each other.
      Sixty-eight patients (33 males, 35 females), mean 12.5 years, were treated in
      four different centers from 1984 to 2001. Twenty-eight patients underwent the ACL
      reconstruction with hamstring grafts, 16 patients with bone-patella-bone
      autografts, 12 patients with quadriceps grafts and 12 patients with facia lata.
      The mean follow-up was 32 months. Postoperative evaluation included radiographs,
      KT-1000/2000 stability measurements, Lysholm score, The Tegner activity scale and
      IKDC score. Neither leg length discrepancy nor angular deformities were noted.
      Mean KT-1000 difference was 2.1 mm, mean postoperative Lysholm knee score 93.3,
      IKDC 87% normal or nearly normal. The Tegner index decreased from 6.6 to 5.7. In
      total, six patients developed instability due to an adequate trauma 1 year after
      the index operation. Two patients showed mild arthrotic changes. All but two
      patients were able to return to the same level of preoperative sports
      participation. None of the four methods studied showed major differences in
      outcome compared to the other. No growth disturbance could be noted.

PMID- 16628460
TI  - Optic pathway glioma: outcome and prognostic factors in a surgical series.
AB  - OBJECTS: The goals of this study were to evaluate the surgical outcomes of optic
      pathway glioma (OPG) and to analyze the prognostic factors related to the
      progression-free survival. MATERIALS AND METHODS: A retrospective review was
      conducted on 33 patients who underwent surgery for OPG; these included 15 male
      and 18 female patients with a mean age of 8.3 years. The mean duration of follow
      up was 52 months. RESULTS AND CONCLUSIONS: The preservation rate of ipsilateral
      vision was 25%, while that of contralateral vision was 83% (P<0.001). There was
      no remarkable endocrine improvement after surgery. The overall and progression
      free survival rates at 5 years were 93.6 and 52.4%, respectively. In our study,
      the predictors for tumor progression were children younger than 5 years of age
      (p=0.023) and of female gender (p=0.022). Because of the variable course of OPG,
      treatment policy should be optimized individually according to patient's status.

PMID- 16628461
TI  - Introduction to the special section: the extended mind and the foundations of
      cognitive science.

PMID- 16628462
TI  - The cognitive cost of extending an evolutionary mind into the environment.
AB  - Clark and Chalmers (1998) have argued that mental states can be extended outside
      an organism's skin. In response to some worries about the availability,
      reliability and portability of such extended resources, Clark (2005) offers a set
      of rough criteria that non-biological objects must fulfil to legitimately ground
      mental states. One such criterion is that the information retrieved from these
      non-biological sources be (more or less) automatically endorsed. But Sterelny
      (2003, 2005) has persuasively argued that the extended sphere is
      epistemologically opaque: a domain of contested truth and deliberate deception.
      As such, retrieving information from this domain requires the deployment of
      social guards for the information to remain reliable. But deploying such guards
      would seem to endanger endorsability by increasing cognitive load. Here I
      demonstrate that deploying social guards does not increase cognitive load if the
      guards are implemented in a highly distributed connectionist economy or off
      loaded to the external environment.

PMID- 16628463
TI  - The biogenic approach to cognition.
AB  - After half a century of cognitive revolution we remain far from agreement about
      what cognition is and what cognition does. It was once thought that these
      questions could wait until the data were in. Today there is a mountain of data,
      but no way of making sense of it. The time for tackling the fundamental issues
      has arrived. The biogenic approach to cognition is introduced not as a solution
      but as a means of approaching the issues. The traditional, and still predominant,
      methodological stance in cognitive inquiry is what I call the anthropogenic
      approach: assume human cognition as the paradigm and work 'down' to a more
      general explanatory concept. The biogenic approach, on the other hand, starts
      with the facts of biology as the basis for theorizing and works 'up' to the human
      case by asking psychological questions as if they were biological questions.
      Biogenic explanations of cognition are currently clustered around two main
      frameworks for understanding biology: self-organizing complex systems and
      autopoiesis. The paper describes the frameworks and infers from them ten
      empirical principles--the biogenic 'family traits'--that constitute constraints
      on biogenic theorizing. Because the anthropogenic approach to cognition is not
      constrained empirically to the same degree, I argue that the biogenic approach is
      superior for approaching a general theory of cognition as a natural phenomenon.

PMID- 16628464
TI  - How do connectionist networks compute?
AB  - Although connectionism is advocated by its proponents as an alternative to the
      classical computational theory of mind, doubts persist about its computational
      credentials. Our aim is to dispel these doubts by explaining how connectionist
      networks compute. We first develop a generic account of computation-no easy task,
      because computation, like almost every other foundational concept in cognitive
      science, has resisted canonical definition. We opt for a characterisation that
      does justice to the explanatory role of computation in cognitive science. Next we
      examine what might be regarded as the "conventional" account of connectionist
      computation. We show why this account is inadequate and hence fosters the
      suspicion that connectionist networks are not genuinely computational. Lastly, we
      turn to the principal task of the paper: the development of a more robust
      portrait of connectionist computation. The basis of this portrait is an
      explanation of the representational capacities of connection weights, supported
      by an analysis of the weight configurations of a series of simulated neural
      networks.

PMID- 16628465
TI  - A new method for detecting causality in fMRI data of cognitive processing.
AB  - One of the most important achievements in understanding the brain is that the
      emergence of complex behavior is guided by the activity of brain networks. To
      fully apply this theoretical approach fully, a method is needed to extract both
      the location and time course of the activities from the currently employed
      techniques. The spatial resolution of fMRI received great attention, and various
      non-conventional methods of analysis have previously been proposed for the above
      named purpose. Here, we briefly outline a new approach to data analysis, in order
      to extract both spatial and temporal activities from fMRI recordings, as well as
      the pattern of causality between areas. This paper presents a completely data
      driven analysis method that applies both independent components analysis (ICA)
      and the Granger causality test (GCT), performed in two separate steps. First, ICA
      is used to extract the independent functional activities. Subsequently the GCT is
      applied to the independent component (IC) most correlated with the stimuli, to
      indicate its causal relation with other ICs. We therefore propose this method as
      a promising data-driven tool for the detection of cognitive causal relationships
      in neuroimaging data.

PMID- 16628466
TI  - Localizing complex neural circuits with MEG data.
AB  - During cognitive processing, the various cortical areas, with specialized
      functions, supply for different tasks. In most cases then, the information flows
      are processed in a parallel way by brain networks which work together integrating
      the single performances for a common goal. Such a step is generally performed at
      higher processing levels in the associative areas. The frequency range at which
      neuronal pools oscillate is generally wider than the one which is detectable by
      bold changes in fMRI studies. A high time resolution technique like
      magnetoencephalography or electroencephalography is therefore required as well as
      new data processing algorithms for detecting different coherent brain areas
      cooperating for one cognitive task. Our experiments show that no algorithm for
      the inverse problem solution is immune from bias. We propose therefore, as a
      possible solution, our software LOCANTO (LOcalization and Coherence ANalysis
      TOol). This new package features a set of tools for the detection of coherent
      areas. For such a task, as a default, it employs the algorithm with best
      performances for the neural landscape to be detected. If the neural landscape
      under attention involves more than two interacting areas the SLoreta algorithm is
      used. Our study shows in fact that SLoreta performance is not biased when the
      correlation among multiple sources is high. On the other hand, the Beamforming
      algorithm is more precise than SLoreta at localizing single or double sources but
      it gets a relevant localization bias when the sources are more than three and are
      highly correlated.

PMID- 16628467
TI  - News from the ROAR lab at the Ohio State University.

PMID- 16628468
TI  - Over-expressed estrogen receptor-alpha up-regulates hTNF-alpha gene expression
      and down-regulates beta-catenin signaling activity to induce the apoptosis and
      inhibit proliferation of LoVo colon cancer cells.
AB  - Epidemiologic studies reported that the prevalence of hereditary non-polyposis
      colon cancer (HNPCC) in male is about 1.5-fold higher than that in female.
      Decreases in circulatory estrogen (E(2)) have been reported to downregulate the
      expression of E(2) receptor (ER) and significantly increase the risk of
      colorectal cancer. Patients that received E(2) replacement therapy were found to
      have a reduction in the incidence of colon adenoma and carcinoma. Furthermore,
      significant decreases in the expression of ER have been found in colorectal
      cancer specimens. Evidences strongly suggest the protective roles of E(2) and ER
      against colorectal cancer. However, the mechanisms of ERalpha effects on
      colorectal cancer cells remained un-clear. LoVo cells were transient transfected
      to overexpress ERalpha, DNA fragmentation and the activated caspases measurements
      were performed to evaluate apoptotic effects. Western blotting was used to
      evaluate protein levels, and luciferase activity assay to measure the Htnf-a
      promoter activity. The results clearly demonstrated that overexpressed ERalpha
      with or without E(2) (10(-8) M) treatment could activate caspase -8, -9, and 3
      and induce DNA fragmentation in LoVo cell. At the same time, overexpressed
      ERalpha plus E(2) significantly increases the expression and promoter activity of
      hTNF-alpha, and the DNA fragmentation effect induced by E(2) plus ERalpha were
      reduced by the addition of hTNF antibody (0.1 ng(ml). In addition, E(2) plus
      ERalpha significantly upregulated p21 and p27 levels and downregulated the beta
      catenin and its target genes, cyclin D1 and Rb, which regulate the cell cycle and
      cell proliferation. The results indicate that E(2) plus overexpressed ERalpha
      induce LoVo cell apoptosis might mediate through the increase of hTNF-alpha gene
      expression, which in turn activate caspase-8, -9 and caspase-3 and lead to the
      DNA fragmentation and apoptosis. E(2) plus ERalpha also showed the downregulation
      of beta-catenin signalings implicating the suppression of proliferation and
      metastasis of colorectal cells. Efforts aiming at enhancing ERalpha expression
      and(or activity may be proved to be an alternative therapy against colorectal
      cancer.

PMID- 16628469
TI  - The effect of Euryale ferox (Makhana), an herb of aquatic origin, on myocardial
      ischemic reperfusion injury.
AB  - Fox nut or gorgon nut (Euryale ferox--Family Nymphaeaceae), popularly known as
      Makhana, has been widely used in traditional oriental medicine to cure a variety
      of diseases including kidney problems, chronic diarrhea, excessive leucorrhea and
      hypofunction of the spleen. Based on the recent studies revealing antioxidant
      activities of Euryale ferox and its glucosides composition, we sought to
      determine if Euryale ferox seeds (Makhana) could reduce myocardial ischemic
      reperfusion injury. Two different models were used: acute model, where isolated
      rat hearts were preperfused for 15 min with Krebs Henseleit bicarbonate (KHB)
      buffer containing three different doses of makhana (25, 125 or 250 microg/ml)
      followed by 30 min of ischemia and 2 h of reperfusion; and chronic model, where
      rats were given two different doses of makhana (250 and 500 mg/kg/day) for 21
      days, after which isolated hearts were subjected to 30 min of ischemia followed
      by 2 h of reperfusion. In both cases, the hearts of the Makhana treated rats were
      resistant to ischemic reperfusion injury as evidenced by their improved post
      ischemic ventricular function and reduced myocardial infarct size. Antibody array
      technique was used to identify the cardioprotective proteins. The Makhana-treated
      hearts had increased amounts of thioredoxin-1 (Trx-1) and thioredoxin-related
      protein-32 (TRP32) compared to the control hearts. Western blot analysis
      confirmed increased expression of TRP32 and thioredoxin proteins. In vitro
      studies revealed that Makhana extracts had potent reactive oxygen species
      scavenging activities. Taken together, the results of this study demonstrate
      cardioprotective properties of Makhana and suggest that such cardioprotective
      properties may be linked with the ability of makhana to induce TRP32 and Trx-1
      proteins and to scavenge ROS.

PMID- 16628474
TI  - Extranodal marginal zone B-cell lymphoma mimicking meningioma in lateral
      ventricle: a case report and possible pathogenesis.
AB  - We report a case of extranodal marginal zone B-cell lymphoma (MZL) mimicking
      meningioma in a lateral ventricle and suggest its possible pathogenesis. The
      patient was a 63-year-old male with seizure attack. MRI showed a 3.5x1.7 cm sized
      homogeneously enhancing mass in the trigon of the right lateral ventricle,
      possibly arising from the choroid plexus. The provisional diagnosis was
      meningioma or metastasis. In the surgical findings, the mass was attached to the
      choroid plexus and totally removed. Pathologic examination revealed a monotonous
      population of medium-sized mononuclear lymphoma cells associated with
      meningothelial whorl formation and neoplastic cells which invaded the
      meningothelial cells. The tumor was immunopositive for CD79a, CD20, CD43 and bcl
      2. We suggest that intracranial extranodal marginal zone B-cell lymphomas might
      mimic meningiomas, because of their relation with the arachnoid cells and that
      meningothelial cells serve as a substitute for the mucosal surface in
      intracranial MALT lymphomas.

PMID- 16628475
TI  - Asterosaponin 1, a cytostatic compound from the starfish Culcita novaeguineae,
      functions by inducing apoptosis in human glioblastoma U87MG cells.
AB  - Malignant glioblastoma is one of the most common malignant tumors in the
      neurological system. Asterosaponin 1, a new cytostatic agent from the starfish
      Culcita novaeguineae appear to exhibit various biological activities, including
      antitumor effect, but the function and mechanism of this new agent on
      glioblastoma cells has not previously been determined. In the present study, we
      investigated the proliferation change of human glioblastoma U87MG cells exposed
      to different concentrations (2.5-20.0 microg/ml) of asterosaponin 1 for a certain
      time. The results showed that asterosaponin 1 significantly suppressed U87MG cell
      proliferation in a time- and dose-dependent manner (IC50 =4.3 microg/ml). Flow
      cytometric analysis of DNA in U87MG cells showed that asterosaponin 1 induces the
      prominent appearance of a sub-G1 peak in the cell cycle suggestive of apoptosis
      identical with the result of annexin V/PI assay. Furthermore, U87MG cells
      treatment with asterosaponin 1 resulted in nuclear condensation with apoptotic
      bodies observed by both fluorescence and electron microscopy. Agarose gel
      electrophoresis of DNA from asterosaponin 1-treated cells revealed a typical
      "ladder" consistent with apoptotic DNA fragmentation. Western-blot staining
      showed asterosaponin 1 decreased the expression of Bcl-2 protein and increased
      the expression of Bax protein. The novel findings suggest that the cytostatic
      actions of asterosaponin 1 toward U87MG cells result from the induction of cell
      apoptosis. Overall, our data demonstrate that asterosaponin 1 is fully equipped
      for an efficient apoptotic killing of glioblastoma cells and suggest that this
      mechanism may play a critical role in anti-tumor chemotherapy.

PMID- 16628476
TI  - Salvage chemotherapy with CPT-11 for recurrent meningioma.
AB  - BACKGROUND: A prospective Phase II study of irinotecan (CPT-11) in adult patients
      with recurrent surgery and radiotherapy-refractory WHO Grade I meningioma.
      METHODS: Sixteen patients (5 men; 11 women) ages 48-70 years (median 62.5), with
      recurrent meningioma were treated. All patients had previously been treated with
      surgery (complete in 4; partial in 9; biopsy in 3) and involved-field
      radiotherapy (median dose 54 Gy; 12 following first surgery and 4 following
      second surgery). Additionally, eight patients underwent re-operation (complete in
      2; partial in 6) and eight patients were treated with salvage stereotactic
      radiosurgery. No patient was treated with prior chemotherapy. CPT-11 was
      administered intravenously every 3 weeks (350 mg/m2/day in patients on non-enzyme
      inducing anticonvulsants [NEIAED]; 600 mg/m2/day in patients on enzyme-inducing
      anticonvulsants [EIAED]) for 9 weeks (operationally defined as a single cycle).
      Neurological and neuroradiographic evaluation were performed every 10 weeks.
      RESULTS: All patients were evaluable. A median of two cycles of CPT-11 (range 1
      4) was administered. CPT-11 related-toxicity (> or = grade 3) included diarrhea
      (6 occurrences, 19% all cycles administered), granulocytopenia (6, 19%),
      leukopenia (5, 16%), thrombocytopenia (3, 10%) and anemia (3, 10%). Four patients
      required transfusion (3 RBC and 1 platelet). One patient developed neutropenic
      fever without bacteriologic confirmation. No treatment-related deaths occurred.
      No patient demonstrated a neuroradiographic complete or partial response (PR), 13
      patients (81%) demonstrated stable disease but disease progressed after 2 cycles
      of CPT-11, and 3 patients (19%) had progressive disease (PD) following a single
      cycle of CPT-11. Time to tumor progression ranged from 2.5 to 5.0 months (median
      5.0 months). Survival ranged from 4 to months (median 7.5 months). CONCLUSIONS:
      The primary objective was to estimate the 6-month progression-free survival (PFS)
      after study entry. As no patient demonstrated PFS at 6-months, the study was
      stopped prematurely as specified by study design. Using CPT-11 in this moderately
      toxic dose schedule failed to demonstrate efficacy in this cohort of adult
      patients with recurrent surgery and radiotherapy-refractory meningioma.

PMID- 16628477
TI  - Chordoid meningioma, an uncommon variant of meningioma: a clinicopathologic study
      of 12 cases.
AB  - AIMS: The study has been undertaken to document the clinicopathological features
      of 12 cases of chordoid meningioma, operated at All India Institute of Medical
      Sciences during 1996 to June 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, mucicarmine, giemsa,
      toluidine blue, alcian blue, reticulin and Masson trichrome. Immunohistochemistry
      for pancytokeratin, epithelial membrane antigen, vimentin, glial fibrillary
      acidic protein, MIB-1, Leucocyte common antigen (LCA), CD-3 and CD-20 was done in
      all cases. RESULTS: The age ranged from 12-67 years (mean 34.2 years) and three
      of them occurred in < 18 years. Male to female ratio was 1:1.4. The duration of
      symptoms varied from 3.5 months to 5 years (mean 14.1 months). No systemic
      symptoms were noted. The location of tumor in eight cases was in the
      supratentorial and rest four in the infratentorial compartments. Interestingly,
      two cases were in intraventricular location, one in the lateral ventricle and
      other in the fourth ventricle. Microscopic examination showed lobulation with
      chordoid elements constituting > 95% of the entire tumor area in 11 of the total
      12 cases. In one case, chordoid pattern constituted about 30% of the total tumor
      area; the rest was predominant meningothelial (60%). Mild to severe
      lymphoplasmacytic cell infiltrate was present in all cases. The histochemical
      stains showed the pattern of acidic mucin and interestingly revealed the presence
      of mast cells both in connective tissue stroma and epithelial cell islands. The
      inflammatory infiltrate was B-cell predominant. MIB-1 labeling index was low (<
      2%) in all cases except two, which showed LI of 6% and 8%. Strong diffuse
      immunoreactivity for vimentin and focal positivity for epithelial membrane
      antigen was noted in all cases. CONCLUSIONS: Chordoid meningiomas are
      predominantly tumors of young adults with predilection for supratentorial
      location. Intraventricular location, absence of systemic manifestations despite
      the presence of abundant B-lymphocytes, presence of mast cells and low MIB-1 LI
      are some of the interesting findings in the present series, which need
      documentation. Hence, larger number of cases with adequate follow-up data need to
      be studied further to establish the clinical significance of this variant.

PMID- 16628481
TI  - Using Carey Temperament Scales to assess behavioral style in children with autism
      spectrum disorders.
AB  - Many researchers have suggested that temperament information could be useful for
      understanding the behavioral variability within the autism spectrum. The purpose
      of this brief report is to examine temperament profiles of 110 children with ASD
      (ages 3-8 years, 61 with Autistic Disorder, 42 with PDD-NOS; and 7 with Asperger
      Disorder) via a commonly used parent report measure of child temperament.
      Internal consistency of temperament dimensions, test-retest reliability,
      descriptions of means and standard deviations are examined, relative to
      previously published norms. Internal consistency of the dimensions and test
      retest reliability were comparable to published norms; however, children with
      autism were rated as presenting with more extreme scores than typically
      developing children on several dimensions. Limitations and implications for
      future work are discussed.

PMID- 16628482
TI  - The use of clarification sessions in the treatment of incest victims and their
      families: an exploratory study.
AB  - The "clarification session" has been implicated as an important component of the
      treatment of families affected by incest. On the basis of information presented
      in clinical literature, however, the specific nature of this intervention varies
      widely. This exploratory study examined the practices and attitudes regarding
      clarification sessions of select members of the Association for the Treatment of
      Sexual Abusers. Surveys were completed by 483 members. Results indicated that
      approximately 77% of respondents had experience in conducting clarification
      sessions. The top two reported reasons for conducting clarification sessions were
      for the perpetrator to assume all responsibility for the abuse and to decrease
      the level of self-blame of the victim. The majority of respondents concurred that
      several activities needed to occur prior to the clarification session, whereas
      less consensus was indicated for activities that were deemed essential during the
      clarification session. Respondents' practices, attitudes, and beliefs are
      discussed in terms of the current state of limited, empirically based knowledge
      in this area. Directions for future research are suggested.

PMID- 16628487
TI  - Chronic schisandrin B treatment improves mitochondrial antioxidant status and
      tissue heat shock protein production in various tissues of young adult and middle
      aged rats.
AB  - The effects of chronic schisandrin B (Sch B) treatment (10 mg/kg/dayx15) on
      mitochondrial antioxidant status and sensitivity to Ca2+-induced permeability
      transition, as well as tissue heat shock protein (Hsp)25/70 production were
      examined in various tissues (brain, heart, liver, skeletal muscle) of young adult
      and middle-aged female rats. Age-dependent impairment in mitochondrial
      antioxidant status, as assessed by levels/activities of antioxidant components
      (reduced glutathione, alpha-tocopherol, Se-glutathione peroxidase and Mn
      superoxide dismutase) and the extent of reactive oxygen species generation in
      vitro, was observed in brain, heart, liver and skeletal muscle tissues. While
      tissue Hsp25 levels remained relatively unchanged with aging, the Hsp70 level was
      increased in both brain and heart tissues of middle-aged rats. Chronic Sch B
      treatment was able to enhance mitochondrial antioxidant status and the resistance
      to Ca2+-induced mitochondrial permeability transition in an age-independent
      manner in various tissues of rats. However, Hsp25 and Hsp70 levels were only
      increased in young adult rats. The Sch B-induced enhancement of mitochondrial
      protective parameters in the heart was associated with the protection against
      myocardial ischemia-reperfusion injury in both young adult and middle-aged rats.
      The results suggest that chronic Sch B treatment may be beneficial for reversing
      the mitochondrial changes with aging and enhancing the heat shock response.

PMID- 16628488
TI  - Dietary restriction would probably not increase longevity in human beings and
      other species able to leave unsuitable environments.
AB  - This article argues that dietary restriction would not increase longevity in
      species able to leave a place where they are subjected to starvation. Human
      beings can emigrate when feeding conditions are a threat to survival and thus
      they would not live longer if subjected to dietary restriction.

PMID- 16628489
TI  - Effects of caloric restriction are species-specific.
AB  - This article addresses two questions: (1) 'can caloric restriction (CR) extend
      the life spans of all species of experimental animals', and (2) 'is CR likely to
      slow the human aging process and/or extend the human life span?' The answer to
      the first question is clearly 'no', because CR decreases the life span of the
      housefly, Musca domestica, and fails to extend the life span of at least one
      mouse strain. The answer to the second question is unknown, because human CR has
      not yet been shown either to increase or curtail the human life span. However,
      recent efforts to develop insect models of CR have been unsuccessful and/or
      relatively uninformative, so any insights regarding the relationship between CR
      and human aging are more likely to arise from studies of established, mammalian
      models of CR.

PMID- 16628493
TI  - Visualization of interphase chromosomes in postmitotic cells of the human brain
      by multicolour banding (MCB).
AB  - Molecular cytogenetics offers the unique possibility of investigating numerical
      and structural chromosomal aberrations in interphase nuclei of somatic cells.
      Previous fluorescence in-situ hybridization (FISH) investigations gave hints of
      numerical chromosomal imbalances in the human brain, present as low-level
      mosaicism. However, as precise identification of aneuploidy rates in somatic
      tissues faces major difficulties due to the limitations of FISH using whole
      chromosome painting or centromeric probes, in this study low-level mosaicism in
      the human brain was addressed for the first time using microdissection-based
      multicolour banding (MCB) probe sets. We demonstrated that MCB is suitable for
      this application and leads to more reliable results than the use of centromeric
      probes in parallel on the same samples. Autosomes and the active X chromosome
      appear as discrete metaphase chromosome-like structures, while the inactive X
      chromosome is condensed in more than 95% of interphase nuclei. The frequency of
      stochastic aneuploidy was found to be 0.2-0.5% (mean 0.35%) per autosome pair, 2%
      for the X chromosome in the female brain, and 0.4% in the male brain, giving a
      cumulative frequency of aneuploidy of approximately 10% in the adult brain.
      Moreover, MCB as well as multi-probe FISH using centromeric probes revealed
      associated signals in a large proportion of brain cells (10-40%). While co
      localized signals could not be discriminated from numerical chromosome imbalances
      after FISH using centromeric probes, interphase MCB allows such differentiation.
      In summary, MCB is the only approach available at present that provides the
      possibility of characterizing the chromosomal integrity of arbitrary interphase
      cell populations. Thus, cytogenetics is no longer limited in its application to
      dividing cells, which is a great step forward for brain research.

PMID- 16628494
TI  - Cytogenetics of the bleak (Alburnus alburnus), with special emphasis on the B
      chromosomes.
AB  - Some of the largest B chromosomes so far discovered in vertebrates are present in
      the cyprinid fish Alburnus alburnus. Previous cytogenetic analyses revealed a
      diploid chromosome number of 2n = 50. In addition, in some individuals one or two
      unusually large B chromosomes are present. Two morphologically different types of
      B chromosomes were observed. The frequency of animals bearing a supernumerary
      chromosome was found to vary considerably between different populations. A more
      detailed analysis of the A and B chromosomes of A. alburnus by conventional
      banding techniques, as well as fluorescence in-situ hybridization (FISH) with the
      telomeric DNA repeats (GGGTTA)7/(TAACCC)7, 18S + 28S rDNA and 5S rDNA were
      performed in the present study. Furthermore, a B chromosome-specific DNA probe
      obtained by amplified length polymorphism (AFLP) was hybridized on metaphases of
      A. alburnus carrying supernumerary B chromosomes. The banding analyses showed
      that the B chromosomes are completely heterochromatic, consist of GC-rich DNA
      sequences, replicate their DNA in the very late S-phase of the cell cycle and are
      composed mainly of a specific retrotransposable DNA element. Finally, blood
      probes from A. alburnus were collected for DNA-flow cytometric measurements. It
      could be shown that the huge supernumerary chromosomes represent nearly 10% of
      the total genome size of A. alburnus.

PMID- 16628495
TI  - High-resolution comparative chromosome painting in the Arizona collared peccary
      (Pecari tajacu, Tayassuidae): a comparison with the karyotype of pig and sheep.
AB  - We used chromosome painting with chromosome-specific probes derived from domestic
      sheep and pig for a high-resolution cytogenetic comparison with the karyotype of
      collared peccary (Pecari tajacu sonoriensis). A reorganization of the karyotype
      involving at least 62-66 conserved segments were observed between the sheep and
      collared peccary. This is an extremely high number compared with other members of
      the same mammalian order (Cetartiodactyla). The comparison between pig and
      collared peccary, both belonging to the Suiformes, however, revealed various
      changes in the gross organization of both karyotypes that may have already
      occurred in a common ancestor of both species suggesting a monophyletic origin of
      Suidae/Tayassuidae. The sheep probes, however, also revealed several
      rearrangements between the two Suidae/Tayassuidae, indicating that these probes
      represent a useful tool for a more detailed analysis of the evolutionary history
      of Suiformes. Our sample of the collared peccary from North America (Arizona,
      USA) showed distinct differences to those already described from South America.
      The chromosome painting results defined a complex translocation that involves
      chromosomes including about one-quarter of the entire collared peccary karyotype.
      This considerable rearrangement indicates subspecies or even species status of
      both peccary populations, as it should present a significant barrier for their
      hybridization.

PMID- 16628496
TI  - Chromosome localization of microsatellite markers in the shrews of the Sorex
      araneus group.
AB  - The extremely high rate of karyotypic evolution that characterizes the shrews of
      the Sorex araneus group makes this group an exceptionally interesting model for
      population genetics and evolutionary studies. Here, we attempted to map 46
      microsatellite markers at the chromosome arm level using flow-sorted chromosomes
      from three karyotypically different taxa of the Sorex araneus group (S. granarius
      and the chromosome races Cordon and Novosibirsk of S. araneus). The most likely
      localizations were provided for 35 markers, among which 25 were each
      unambiguously mapped to a single locus on the corresponding chromosomes in the
      three taxa, covering the three sexual chromosomes (XY1Y2) and nine of the 18
      autosomal arms of the S. araneus group. The results provide further evidence for
      a high degree of conservation in genome organization in the S. araneus group
      despite the presence of numerous Robertsonian rearrangements. These markers can
      therefore be used to compare the genetic structure among taxa of the S. araneus
      group at the chromosome level and to study the role of chromosomal rearrangements
      in the genetic diversification and speciation process of this group.

PMID- 16628497
TI  - Chromosome microdissection identifies genomic amplifications associated with drug
      resistance in a leukemia cell line: an approach to understanding drug resistance
      in cancer.
AB  - A significant problem encountered in the treatment of cancer patients is that
      cancer cells often evolve resistance to chemotherapeutic agents. One of the
      mechanisms responsible for drug resistance is gene amplification. The study of
      the behavior of genes conferring drug resistance is very important to determine
      future treatments for cancer patients that will minimize the effect of gene
      amplification. One of the best methods to investigate this phenomenon is to use
      chromosome microdissection to directly access the amplified gene or genes. In the
      present study, chromosome microdissection and fluorescent in-situ hybridization
      (FISH) were applied for the identification of genes residing in a homogeneously
      staining region (HSR) in drug-resistant cell sublines developed by treatment of
      the T-cell leukemia cell line CCRF-CEM with increasing levels of the
      anthracycline, epirubicin. We have demonstrated that the selection by epirubicin
      actually elevated the level of the multidrug resistance-associated protein (MRP1)
      gene. We argue that the breakage fusion bridge (B-F-B) cycle offers a plausible
      explanation for this amplification. The DNA prepared from the amplified regions
      by chromosome microdissection provides a resource for future investigations
      looking for the possible presence of novel genes contributing to drug resistance.

PMID- 16628498
TI  - Characterization of a complex rearrangement with interstitial deletions and
      inversion on human chromosome 1.
AB  - Deletion of the distal band of the short arm of chromosome 1 (monosomy 1p36) is
      the most common terminal deletion syndrome, occurring in about 1 in 5000
      newborns. Of the 121 subjects ascertained for our study to date, 12 (9.9%) have
      interstitial deletions, three of which are complex rearrangements showing more
      than one deletion. Herein we report the characterization of a complex
      rearrangement with two interstitial deletions in the same chromosome 1p36.33
      p36.23. We narrowed and analyzed the breakpoints and junctions between the
      sequence fragments involved in the rearrangement to determine the structure of
      this deleted chromosome 1. The analyses of the DNA sequence at the junctions
      showed additional complexity: an inversion and a third de-novo interstitial
      deletion. We reconstructed this complex rearrangement of 1p36 to understand the
      mechanism of formation. Analysis of the breakpoint junctions revealed that three
      of the four breakpoints each interrupted a gene. Alignments of the junctions
      showed the lack of any sequence similarity between the breakpoints, suggesting
      the involvement of non-homologous end joining (NHEJ) in the ligation of broken
      ends following deletion. The identification of translin recognition sites in the
      breakpoints suggests translin involvement in the repair of broken chromosomes.
      This report is one of the first to examine constitutional chromosomal
      rearrangements at the DNA sequence level. The discovery of cryptic events in
      seemingly simple chromosome rearrangements may provide the basis for proposing
      mechanisms of formation.

PMID- 16628499
TI  - Comparative genome maps of the pangolin, hedgehog, sloth, anteater and human
      revealed by cross-species chromosome painting: further insight into the ancestral
      karyotype and genome evolution of eutherian mammals.
AB  - To better understand the evolution of genome organization of eutherian mammals,
      comparative maps based on chromosome painting have been constructed between human
      and representative species of three eutherian orders: Xenarthra, Pholidota, and
      Eulipotyphla, as well as between representative species of the Carnivora and
      Pholidota. These maps demonstrate the conservation of such syntenic segment
      associations as HSA3/21, 4/8, 7/16, 12/22, 14/15 and 16/19 in Eulipotyphla,
      Pholidota and Xenarthra and thus further consolidate the notion that they form
      part of the ancestral karyotype of the eutherian mammals. Our study has revealed
      many potential ancestral syntenic associations of human chromosomal segments that
      serve to link the families as well as orders within the major superordinial
      eutherian clades defined by molecular markers. The HSA2/8 and 7/10 associations
      could be the cytogenetic signatures that unite the Xenarthrans, while the
      HSA1/19p could be a putative signature that links the Afrotheria and Xenarthra.
      But caution is required in the interpretation of apparently shared syntenic
      associations as detailed analyses also show examples of apparent convergent
      evolution that differ in breakpoints and extent of the involved segments.

PMID- 16628500
TI  - Contrast between extensive variation of 28S rDNA and stability of 5S rDNA and
      telomeric repeats in the diploid-polyploid Squalius alburnoides complex and in
      its maternal ancestor Squalius pyrenaicus (Teleostei, Cyprinidae).
AB  - The diploid-polyploid Squalius alburnoides complex resulted from interspecific
      hybridization. The chromosomal mapping of 28S and 5S ribosomal genes and of
      (TTAGGG)n telomeric repeats was performed on specimens from the complex and from
      the sympatric bisexual species S. pyrenaicus (the complex maternal ancestor) as
      part of an investigation of the evolutionary relationships between genomic
      constitutions and the consequences of the ongoing polyploidization process in
      terms of chromosome reshaping. Contrasting results were obtained. While results
      with 5S rDNA and telomeric probes gave an impression of genomic stability, the
      variability detected with 28S rDNA probe suggested quite the opposite. The 5S
      rDNA probe mapped constantly to three chromosomes per haploid genome with
      apparently conserved locations in morphologically similar chromosomes;
      conversely, prominent intra- and inter-individual variations of 28S rDNA and of
      syntenic sites with 5S rDNA were detected with regard to number, size and
      location. Hypotheses for the causes of such polymorphisms are discussed. The
      terminal position of most 28S rDNA sites and the absence of detectable
      interstitial telomeric sequences suggest a mechanism that does not involve major
      chromosomal rearrangements. These fishes share similar patterns for the studied
      cytogenetic markers which may be taken as evidence of an apparent stability that
      may be hiding extensive and subtle genome variations that are possibly related to
      an ongoing evolutionary process of genome tetraploidization and speciation.

PMID- 16628501
TI  - Ac-like transposons in populations of wild diploid Triticeae species: comparative
      analysis of chromosomal distribution.
AB  - Data are presented on the intra- and interspecific differences/similarities in
      chromosomal patterns of Ac-like elements (hAT family) in ecologically contrasted
      populations of three Triticeae species - Aegilops speltoides, Triticum urartu,
      and Hordeum spontaneum. Application of original computer software made it
      possible to precisely map transposon clusters and to link them to known
      chromosomal markers (rDNA sites, centromeres, and heterochromatin regions). From
      our data we can specify the most visible features of Ac-like elements chromosomal
      distribution: preferential concentration in chromosomal proximal regions; high
      percentage of clusters on the border between euchromatin and heterochromatin;
      complementary chromosomal arrangement towards En/Spm transposons (CACTA);
      population-specific insertions into centromeres; more differences in total
      cluster numbers between populations of self-pollinated species than between
      populations of cross-pollinated species. The application of statistical
      simulation (Resampling) method to analysis of data indicates that ecology may
      play a certain role in dynamics of Ac-like elements. Comparison of real Ayala
      distances, as well as real chromosomal distribution of Ac-like elements in
      populations of two species with different mating systems with the same but
      randomly simulated parameters, revealed that non-random population structure in
      the Mediterranean floral zone suffers and becomes chaotic in the Irano-Turanian
      zone.

PMID- 16628502
TI  - Histone deacetylase activity is necessary for chromosome condensation during
      meiotic maturation in Xenopus laevis.
AB  - Chromosome condensation is thought to be an essential step for the faithful
      transmission of genetic information during cellular division or gamete formation.
      The folding of DNA into metaphase chromosomes and its partition during the cell
      cycle remains a fundamental cellular process that, at the molecular level, is
      poorly understood. Particularly, the role of histone deacetylase (HDAC)
      activities in establishing and maintaining meiotic metaphase chromosome
      condensation has been little documented. In order to better understand how
      metaphase chromosome condensation is achieved during meiosis, we explored, in
      vivo, the consequences of HDAC activities inhibition in a Xenopus oocyte model.
      Our results show that deacetylase activity plays a crucial role in chromosome
      condensation. This activity is necessary for correct chromosome condensation
      since the earlier stages of meiosis, but dispensable for meiosis progression,
      meiosis exit and mitosis entry. We show that HDAC activity correlates with
      chromosome condensation, being higher when chromosomes are fully condensed and
      lower during interphase, when chromosomes are decondensed. In addition, we show
      that, unlike histone H4, Xenopus maternal histone H3 is stored in the oocyte as a
      hypoacetylated form and is rapidly acetylated when the oocyte exits meiosis.

PMID- 16628503
TI  - [Clinical symptoms of the supratentorial arteriovenous malformations and factors
      influencing their occurrence].
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess frequency of main
      symptoms of the supratentorial arteriovenous malformations (AVM) and attempt to
      find factors influencing their occurrence. MATERIAL AND METHODS: 88 consecutive
      patients operated on for AVM located supratentorially in the years 1983-2000 were
      included in a retrospective analysis. Statistical analyses including chi-square
      test and exact Fisher test were performed for comparisons among groups. RESULTS:
      The most common cause of diagnostics was intracranial hemorrhage--62.5%.
      Epilepsy, headaches and non-hemorrhagic focal deficits were described in 38.6%,
      9.1% and 4.5%, respectively. Deterioration (focal deficits and/or disturbances of
      consciousness) after hemorrhage occurred in 30%. The risk of hemorrhage from AVM
      was 2.2% per year. Hemorrhage was more frequent in the cases of small size (<3
      cm) of AVM (p=0.001), deep location (p<0.05) and when single (p=0.001) and
      exclusively deep (p<0.05) venous drainage were present. However, superficial
      location of AVM and nidus size >3 cm significantly influenced epilepsy occurrence
      (p<0.05 and p=0.001, respectively). Sex and coexisting aneurysm did not influence
      occurrence of epilepsy or hemorrhage. CONCLUSIONS: Supratentorial AVMs manifest
      most common as intracranial hemorrhage and epilepsy. Factors increasing the risk
      of hemorrhage are: small size, deep location of AVM, single and exclusively deep
      venous drainage. Factors increasing the risk of epilepsy are: superficial
      location and size >3 cm.

PMID- 16628504
TI  - [The microsurgical treatment of the supratentorial arteriovenous malformations.
      Part I--early and late results].
AB  - BACKGROUND AND PURPOSE: The aim of this study was an analysis of early and late
      results of the microsurgical treatment of arteriovenous malformations (AVM)
      located supratentorially and factors that may influence the outcome. MATERIAL AND
      METHODS: 88 consecutive patients operated on in the years 1983-2000 for
      supratentorial AVM located were included in a retrospective analysis. All
      patients underwent microsurgical selective removal of AVM without prior
      embolization. The outcome was assessed on the day of discharge according to the
      Glasgow Outcome Scale (GOS) and at least 6 months after surgery according to the
      Karnofsky Scale (KS). RESULTS: A satisfactory outcome (GR+MD in GOS) was achieved
      in 92%. A severe deficit appeared in 4.5% and 3 (3.4%) patients died. The only
      factor influencing satisfactory outcome was low grade of AVM (I-II) in the
      Spetzler-Martin scale (p<0.0001). Factors influencing the excellent outcome (GR
      in GOS) are: size of AVM<3 cm (p=0.02), non-eloquent location (p=0.001) and
      exclusively superficial venous drainage (p=0.04). There was no case of
      deterioration in the late period. In 3/4 of patients discharged with deficit, a
      significant improvement was observed: a mild deficit withdrew in 13 of 17, and a
      severe deficit withdrew in 3 of 4. A satisfactory outcome in final assessment
      (KS>70%) was achieved in 95.5%, severe disabling deficit (KS 50%) remained in
      1.1%. CONCLUSIONS: Results of the surgical treatment of AVM are satisfactory,
      especially in I and II grade of the Spetzler-Martin scale. In these cases
      microsurgical removal should be the method of choice, because immediately after
      treatment the risk of further hemorrhage is eliminated. Postoperative deficits
      withdraw during weeks or months in most cases and the final satisfactory result
      was achieved in 95% of patients.

PMID- 16628505
TI  - [The microsurgical treatment of the supratentorial arteriovenous malformations.
      Part II--complications].
AB  - BACKGROUND AND PURPOSE: The aim of this study was an analysis of complications
      after surgical treatment of the cerebral supratentorial arteriovenous
      malformations (AVM), assessment of their clinical sequelae, and attempt to find
      factors influencing their occurrence. MATERIAL AND METHODS: 88 consecutive
      patients operated on for AVM in the years 1983-2000 were included in a
      retrospective study. In all patients microsurgical, selective removal of AVM was
      performed, without prior embolization. The statistical analysis was carried out
      by means of exact Fisher test and c2 test. RESULTS: Complications in the
      postoperative period were observed in 45.5%, including short-term deterioration
      (27.3%) and symptoms present till the day of discharge (18.2%). Mechanisms of
      deterioration were as follows: significant intraoperative hemorrhage (5.7%),
      hemodynamic disturbances after AVM removal (20.5%) and resection of AVM in the
      eloquent area (19.3%). Many variables that may contribute to the complications
      were studied. Factors increasing the risk of significant intraoperative
      hemorrhage are: steal effect visible in angiography (32% vs. 10%, p<0.05),
      intraventricular penetration of AVM (38% vs. 11%, p<0.05). Factors increasing the
      risk of hemodynamic disturbances are: feeding from the medial cerebral artery
      (MCA) (31% vs. 8%, p=0.02) and complex venous drainage (32% vs. 14%, p=0.05).
      CONCLUSIONS: The most common causes of postoperative deterioration are
      hemodynamic disturbances after AVM removal and manipulation in the eloquent area.
      Hemodynamic disturbances worsened the prognosis significantly, and were the only
      cause of mortality (3.4%). However, massive intraoperative hemorrhage and
      operation in the eloquent area did not influence the outcome significantly. Risk
      factors for intraoperative hemorrhage are steal effect and intraventricular
      penetration of AVM. Risk factors for hemodynamic disturbances are feeding AVM
      from MCA and complex venous drainage.

PMID- 16628506
TI  - [Concentration of the beta-chemokine CCL5 (RANTES) in cerebrospinal fluid in
      patients with tick-borne encephalitis].
AB  - BACKGROUND AND PURPOSE: In tick-borne encephalitis (TBE), perivascular
      infiltrates are formed within the central nervous system (CNS) and are
      accompanied by pleocytosis with a predominance of T CD4+ lymphocytes in
      cerebrospinal fluid (CSF). Factors responsible for leukocyte flow into CNS in TBE
      have not been investigated. We evaluated the concentration of the chemotactic
      factor for lymphocytes, chemokine CCL5 (RANTES, Regulated upon Activation, Normal
      T cell Expressed and Secreted) in CSF and serum of patients with TBE and assessed
      its correlation with CSF pleocytosis. MATERIAL AND METHODS: Group I consisted of
      10 patients with TBE virus infection presenting as meningitis; group II included
      11 patients with TBE presenting as encephalomeningitis or
      myeloencephalomeningitis. The control group consisted of 8 patients, in whom
      neuroinfection and infection with TBE virus was excluded. The concentration of
      CCL5 was measured by ELISA in CSF and serum samples taken within 24 hours after
      hospitalization (examination 1) and in the convalescence period, on average after
      16 days (examination 2). RESULTS: Mean CCL5 concentration in serum did not differ
      between the groups, while in CSF it was significantly increased in group I
      (64.3+/-75.5 pg/ml in examination 1 and 44.4+/-39.5 pg/ml in examination 2) and
      in group II (38.4+/-17.0 pg/ml in examination 1 and 48.8+/-24.7 pg/ml in
      examination 2) in comparison with controls (3.7+/-5.3 pg/ml). There was no
      significant difference regarding CCL5 concentration between groups I and II and
      between the examination 1 and 2. There was no correlation between the
      concentration of CCL5 and CSF parameters. CONCLUSIONS: The concentration of CCL5
      is increased in CSF, but not in serum of patients with TBE. This increase does
      not depend on the clinical form of the disease and is sustained after the
      disappearance of the symptoms of acute infection. Further studies are necessary
      to determine the source of CCL5, and its role in the pathogenesis of TBE and its
      sequelae.

PMID- 16628507
TI  - [Computer-based rehabilitation of cognitive impairments and motor arm function of
      patients with hemiparesis after stroke].
AB  - OBJECTIVE: To evaluate the usefulness of the computer program made for the
      patients after stroke to treat their cognitive impairments and hemiparesis.
      RESEARCH DESIGN AND METHODS: The experimental group involved 10 patients after
      stroke who were obliged to train on a computer every day during their three-week
      stay on the rehabilitation ward. The control group involved 10 patients after
      stroke who did not participate in any computer training during their
      rehabilitation process. The first part of the computer tasks trains the attention
      impairments and visual-motor co-ordination problems. We modified the joystick by
      adding special buttons to train movements of the wrist, thumb and forefinger of
      the impaired hand. Computer tasks are made in the way to stimulate both the
      cognitive functions and hand dexterity at the same time. RESULTS: This initial
      research shows a statistically significant improvement of the cognitive functions
      and hand dexterity among patients from the experimental group. According to these
      results we did not observe any significant improvement in the cognitive functions
      among patients who did not train on a computer (control group). CONCLUSIONS: The
      results of this research suggest the usefulness of this computer program in
      training cognitive impairments and visual-motor co-ordination as well as hand
      dexterity among the patients after stroke.

PMID- 16628508
TI  - [Unilateral thalamotomy for the treatment of tremor dominant Parkinson's
      disease].
AB  - BACKGROUND AND PURPOSE: To assess the effectiveness of unilateral thalamotomy for
      the treatment of parkinsonian tremor and other motor signs of Parkinson's disease
      (PD). MATERIAL AND METHODS: Between 1999 and 2004, 41 patients with idiopathic
      tremor dominant PD were treated surgically in the Neurosurgical Department of
      Postgraduate Medical Center in Warsaw. Stereotactic thalamotomy was performed
      with Leksell stereotactic frame (model G) using intraoperative macrostimulation.
      The patients were assessed according to the Unified Parkinson's Disease Rating
      Scale version 3. (UPDRS) before and after thalamotomy in the off state. The
      progression of PD was also evaluated according to the Hoehn and Yahr scale in the
      off state and also Schwab and England was used to assess the disability of the
      patients. The patients were evaluated before thalamotomy in the off state, and 3,
      12, 24 and 36 months after surgery, according to the above mentioned clinical
      rating scales. RESULTS: The authors report their results among 41 patients who
      underwent stereotactic thalamotomy 3 years postoperatively. At 3 years follow-up
      (in the group of 19 patients) the contralateral tremor from the presurgical value
      of 11.2 (items 20 - 21 UPDRS) decreased to 2.6. The rigidity in contralateral
      limbs at 3 years follow-up was 1.7 (item 22 UPDRS) when compared to 2.8 (item 22
      UPDRS) preoperative value. Thalamotomy had no effect on bradykinesia or other
      manifestations of PD such as balance or gait disturbance. There were 13 transient
      and 6 permanent complications. CONCLUSIONS: Thalamotomy using intraoperative
      macrostimulation in carefully selected patients is a beneficial operation for the
      control of medically refractory parkinsonian resting and postural tremor. The
      effect of unilateral thalamotomy on tremor is long lasting.

PMID- 16628509
TI  - [Posturography as objective evaluation of the balance system in Parkinson's
      disease patients after neurosurgical treatment. A preliminary report].
AB  - BACKGROUND AND PURPOSE: In advanced stages of Parkinson's disease (PD) beside
      resting tremor, rigidity, and bradykinesia, most patients reveal severe balance
      instability. The goal of this study is to determine objectively postural control
      changes using static posturography after neurosurgical treatment (unilateral
      posteroventrolateral pallidotomy). MATERIAL AND METHODS: 15 patients with
      advanced idiopathic PD underwent unilateral posteroventrolateral pallidotomy. The
      study group was composed of 8 men and 7 women. The mean disease duration until
      operation was 12.5+/-3.5 years, and the mean age of the patients at the time of
      surgery was 65.8+/-4.1 years. Postural control changes were assessed objectively
      by static computerized posturography and subjectively according to items of
      posture, gait and postural stability derived from Part III (motor examination)
      UPDRS. All evaluations of the balance system were performed preoperatively in the
      off and on condition, and also two weeks postoperatively in the same conditions.
      RESULTS: It was found that the majority of posturographic parameters in the off
      condition were improved after neurosurgical treatment. The improvement in the on
      condition was less pronounced. For example, the mean path length in the off
      condition during eyes opened was 318+/-159 mm before pallidotomy, and after
      surgery it was 240.9+/-119.2 mm in off. The difference was statistically
      significant (p < 0.005, t=3.11). CONCLUSIONS: Pallidotomy improves postural
      control changes in the early postoperative period, which can be proved by static
      computerized posturography.

PMID- 16628510
TI  - [Complications of a transpedicular stabilization of thoraco-lumbar burst
      fractures].
AB  - Complications of transpedicular stabilizations of thoraco-lumbar burst fractures
      are presented on the basis of literature review and own experiences. Unstable
      thoraco-lumbar burst fractures create the most difficult biomechanical conditions
      for a stabilizer. A literature review was done to estimate the effectiveness of
      vertebral body height restoration and its maintenance, the effectiveness of
      transpedicular grafting, the fusion rate and the implant-related complications
      rate. Transpedicular stabilization systems demonstrate a marked stiffness in all
      directions which is greater than in the case of other posterior stabilization
      systems. During the postero-lateral spondylodesis the transpedicular stabilizer
      is gradually unburdened but it is still loaded even after the completion of the
      bone fusion. A support of the anterior spinal column markedly diminishes the
      loads of the stabilizer and improves the segmental stability. Long-term follow-up
      studies of transpedicularly stabilized burst fractures reveal a deterioration of
      primarily good corrections. In some cases the correction returns to the level
      from before the operation in spite of transpedicular bone grafting. The implant
      related complications rate (screw or rod breakages and a loss of
      interconnections) reaches up to 28 % of cases. In order to improve the anterior
      column stability and limit late kyphotization, as well as avoid implant-related
      complications, some authors additionally recommend performing a posterior
      interbody fusion (PLIF) or an anterior corpectomy with stabilization. Posterior
      transpedicular stabilization of thoraco-lumbar burst fractures does not provide a
      complete stabilization of the anterior spinal column, which results in a
      recurrence of spine kyphotization and implant-related complications. In selected
      cases, the application of an additional anterior column support markedly relieves
      the transpedicular fixator and reduces the pseudoarthrosis rate, late
      kyphotization and implant-related complications simultaneously.

PMID- 16628511
TI  - [The role of social support in the quality of life after stroke. A review of
      selected experimental research].
AB  - Surviving of a stroke may be considered as a major stressful life event.
      Neurological and functional deficits often lead to a loss of independence, social
      alienation, depression and deterioration of the quality of life. Earlier
      correlational studies have shown that social support may mediate responses to
      stroke and improve patients' quality of life. The aim of this article was to
      review randomized controlled trials (RCTs) concerning the role of professional
      social support in the quality of life after stroke. The vast majority of the RCTs
      published in the last decade did not show any positive impact of support on the
      psychosocial consequences of a stroke. It does not mean, however, that
      professional support is necessarily ineffective. The reviewed RCTs may fail to
      detect benefits because of some methodological and theoretical limitations. There
      is a need of further research but more attention should be given to a power
      analysis, selection of an appropriate outcome measure and standardisation of a
      study procedure. It is also important to found research deliberately on existing
      social support theories.

PMID- 16628512
TI  - [Carbamazepine-induced systemic lupus erythematosus--a case report].
AB  - Epileptic seizures may be an early symptom of systemic lupus erythematosus, while
      at the same time some of the epileptic drugs, namely carbamazepine (CBZ),
      phenytoin (PHT), valproic acid (VPA), ethosuximide (ETM), primidone (PRM),
      lamotrigine (LTG), zonisamide (ZNS) can cause lupus. A separate clinical problem
      is the fact that few cases of systemic lupus have as yet been identified by
      giving antiepileptic drug. We present the case of a 30-year-old woman with
      frequent simple partial seizures and few secondarily generalized seizures since
      the age of 18. She was treated with VPA for three years. Then, because of side
      effects the drug had to be withdrawn and was replaced by CBZ. After eight months
      duration of the treatment with CBZ, the dose was increased because a secondarily
      generalized seizure occurred again. After another two months, painful swelling of
      all joints and leucopenia were observed. During additional studies, LE cells and
      high titer of ANA antibodies were found. Systemic lupus erythematosus was
      diagnosed and prednisone therapy was introduced. In spite of the withdrawal of
      CBZ, the increased titer of ANA antibodies persisted for several years and skin
      and muscle biopsy performed five years from the onset of clinical symptoms
      disclosed inflammatory infiltration and presence of IgG and IgM deposits in skin
      and vessel walls. Control serological examinations, skin and muscle biopsy
      carried out after eight years of observation and lack of clinical manifestations
      permitted to exclude a connective tissue disease in our patient.

PMID- 16628513
TI  - [Reversible demyelinisation of corpus callosum in the course of Marchiafava
      Bignami disease].
AB  - Marchiafava-Bignami disease is a rare disorder of an unknown aetiology that is
      marked by focal demyelinisation in the corpus callosum. Chronic alcohol abuse
      plays an important role in its development. Its course is unfavourable, although
      rare cases of clinical improvement confirmed in MRI have been reported. Until
      now, no case of Marchiafava-Bignami disease diagnosed intra vitam was so far
      described on the territory of Poland. The authors present such a case with
      favourable course. A 52-year-old male with chronic alcoholism was hospitalised
      due to altered consciousness which developed subacutely prior to admission. The
      first MRI scans yielded demyelinating lesions in the corpus callosum. The
      clinical and radiological findings were consistent with the diagnosis of
      Marchiafava-Bignami disease. Thiamine, vitamin B12, folic acid and amantadine
      were administered, which resulted in an improvement in both motor and cognitive
      functions. Control MRI scans revealed remyelinisation of the corpus callosum.
      Hence, this technique proved itself to be useful in monitoring the course of the
      disease.

PMID- 16628514
TI  - [Pathophysiology of respiration with special reference to sleep related breathing
      disorders].

PMID- 16628515
TI  - [Current trends in the diagnosis of sleep related breathing disorders].

PMID- 16628516
TI  - [Use of oral appliances in therapy of sleep related breathing disorders].

PMID- 16628517
TI  - [Surgical therapy of sleep related breathing disorders - a critical observation].

PMID- 16628518
TI  - [Perioperative risks and management of patients with sleep related breathing
      disorders].

PMID- 16628519
TI  - [Differential use of positive airway (PAP) in sleep related breathing disorders
      with obstruction of the upper airways].

PMID- 16628520
TI  - [Sleep related breathing disorders without obstruction of the upper airways -
      peculiarities in diagnosis and therapy].

PMID- 16628521
TI  - [Sleep disorders in childhood with special reference to sleep related breathing
      disorders].

PMID- 16628525
TI  - Classification of headache disorders.
AB  - Clinical diagnostic classifications are critical when clear biological markers
      are not available. Such is the case in many headache disorders and mental
      disorders. Also, it is crucial that the classification is widely accepted and
      utilized. A main goal of classification is to be a universal language for
      categorizing a disease or a set of disorders, establishing diagnostic criteria,
      and promoting unity in treatment. The International Headache Society published
      its first Classification of Headache Disorders in 1988 and its second edition in
      2004. The first classification paved the way for a better understanding of the
      epidemiology, mechanisms, and treatment of headache disorders, and the second
      edition likely will magnify our knowledge. This article provides an overview of
      the classification system and outlines some of the major changes in the revised
      edition.

PMID- 16628526
TI  - When and how to investigate the patient with headache.
AB  - The very common symptom of headache most often has a benign cause and can usually
      be diagnosed following a thorough history and neurologic and focused general
      physical examinations. Because the potential etiologies can threaten life and
      neurological function, headaches provoke understandable concern on the part of
      the patient and health care provider. Thoughtful testing can exclude the
      worrisome underlying causes. This article reviews the neurological and general
      symptoms and signs that should prompt diagnostic testing and the specific
      diagnostic studies that are recommended. The worrisome factors include recent
      head or neck injury; a new, worse, worsening, or abrupt-onset headache; headache
      brought on by exertion or Valsalva maneuver/cough; new headache in the patient
      over the age of 50; neurological symptoms and/or abnormal signs; systemic
      symptoms and/or signs; and secondary risk factors such as a history of cancer or
      human immunodeficiency virus infection. Less worrisome are headaches that wake
      the patient from sleep at night, side-locked headaches, and prominent effect of
      change in posture on the pain. The diagnostic investigations include
      neuroimaging, cerebrospinal fluid examination, and blood testing in specific
      situations.

PMID- 16628527
TI  - Pathophysiology of migraine.
AB  - The cause and pathophysiology of migraine are not well understood. Over the years
      research into migraine pathophysiology has focused on the physiology and
      pharmacology of the headache, the changes in cerebral cortex associated with the
      symptoms of the aura, and more recently the genetics underlying the migraine
      syndromes. In this discussion, the neuroanatomical structures activated during
      migraine attacks, the traditional theories of migraine that serve as the
      foundation for current research, and the essential findings from current migraine
      pathophysiological research will be reviewed. Investigations in migraine can be
      divided into those related to the brain events initiating a migraine attack,
      those examining the mechanisms of activation and transmission within trigeminal
      afferent neurons, and those focused on the effect of and the modulation of
      nociception trigeminal input within the central nervous system.

PMID- 16628528
TI  - Acute therapy for migraine headaches.
AB  - The migraine attack is made up of phases, which include the prodrome, aura, and
      the headache itself. Not every migraineur experiences each phase. Each phase has
      its own distinct pathogenesis and its own unique acute therapy. The acute therapy
      for each phase of the migraine attack will be discussed.

PMID- 16628529
TI  - Prophylactic pharmacotherapy for migraine headaches.
AB  - Migraine therapeutics are pharmacological, including acute and preventive,
      nonpharmacological and/or both. Preventive pharmacological strategies
      serendipitously were discovered to be effective and include drugs from various
      pharmacological classes (e.g., beta-adrenergic blocker, anticonvulsant, tricyclic
      antidepressants, serotonin receptor antagonist). Converging level I evidence and
      clinical experience support the use of the antidepressant amitriptyline, the
      anticonvulsants divalproex and topiramate, and the beta-adrenergic blockers
      propranolol, timolol, and metoprolol in migraine prevention. Other options for
      migraine prophylaxis exist, but the level of evidence in support of their use is
      not as robust. All of these drugs have varying degrees of adverse effects, some
      of which can limit their use. Balancing potential efficacy with risk of adverse
      effects, addressing patients' expectations and desires, complying with management
      recommendations, adequate follow up, and accurate assessment of treatment goals
      are key to migraine prevention. Finally, future migraine-preventive drugs likely
      will target migraine mechanisms more specifically, which undoubtedly will enhance
      the therapeutic index.

PMID- 16628530
TI  - Behavioral approaches to the treatment of migraine.
AB  - Behavioral interventions such as biofeedback training, relaxation training, and
      cognitive-behavior stress management therapy have been identified as efficacious
      treatments for migraine headache. These treatments, and the formats (clinic
      based, limited-contact, and home-based) in which they are taught, are described
      in this article. Information about public health interventions (school, work,
      Internet, and mass media) is also briefly addressed. Results of studies examining
      the efficacy of behavioral treatments, how behavioral treatments compare in
      effectiveness, and how they can be integrated with pharmacotherapy are reviewed
      for both adult and pediatric populations. Finally, the role of behavioral
      treatments in migraine treatment guidelines is discussed, and factors that are
      associated with response to behavioral treatments are reviewed.

PMID- 16628531
TI  - Sporadic and familial hemiplegic migraine: diagnosis and treatment.
AB  - Hemiplegic migraine is a rare subtype of migraine with aura associated with
      transient hemiplegia. The weakness is caused by motor aura. Hemiplegic migraine
      is the only headache syndrome associated with known genetic mutations and serves
      as a model for understanding more common varieties of migraine. Because the
      phenotype includes striking yet transient neurological signs and symptoms, it is
      imperative that clinicians know the differential diagnosis to rule out possible
      secondary etiologies when treating patients with hemiplegic spells. Hemiplegic
      migraine occurs with equal prevalence in either a sporadic or familial form
      differentiated only by family history. Thus far, treatment trials are anecdotal,
      although verapamil and acetazolamide have shown promise.

PMID- 16628532
TI  - Special considerations in the treatment of migraine in women.
AB  - Nearly 32 million Americans have migraine, 24 million of whom are women who
      suffer with migraine throughout their lifetimes. Prior to puberty, girls are
      afflicted with migraine at approximately the same rate as boys, but after puberty
      there is an emerging female predominance. Although hormones do not entirely
      explain the epidemiological variation seen in migraine, estrogen certainly plays
      an important role. Given the hormonal changes occurring throughout a woman's
      life, there are many opportunities for a hormonal impact on migraine, including
      menarche, oral contraceptive use, pregnancy, perimenopause, and menopause. The
      special considerations of migraine in women will be reviewed including
      epidemiology, pathophysiology, diagnosis, and therapy.

PMID- 16628533
TI  - Episodic and chronic migraine in children.
AB  - Migraine headaches occur frequently in both preschool and school-aged children.
      Although some symptoms of migraines may change with age, they are typically
      characterized by severe headaches in an ill-appearing child associated with
      photophobia and nausea and are relieved by sleep. In late childhood and
      adolescence, the headaches of some patients will transform into a chronic daily
      headache or chronic migraine. Treatment consists of identifying environmental
      triggers, providing appropriate pain relief, and the judicious use of
      preventative medications.

PMID- 16628534
TI  - Pathophysiology and management of transformed migraine and medication overuse
      headache.
AB  - There is considerable overlap in the mechanisms mediating migraine headache pain
      and sustained opioid-induced paradoxical pain. Both involve upregulation of
      calcitonin gene-related peptide and increased excitability of dorsal horn
      neurons. Descending facilitation from the rostral ventromedial medulla may
      contribute to this increased excitability. Using special magnetic resonance
      imaging techniques, high iron levels were found in the periaqueductal gray of
      patients with chronic daily headache with medication overuse. The periaqueductal
      gray is the center of a powerful descending antinociceptive neuronal network and
      projects to the rostral ventromedial medulla and subsequently to the dorsal horn.
      The periaqueductal gray is also involved in the behavioral response to opiate
      withdrawal. Dysfunction in the periaqueductal gray may explain why frequent
      analgesic use can result in medication overuse headache in migraineurs.
      Management of transformed migraine with medication overuse involves patient
      education, biobehavioral therapy, withdrawal of overused acute medications,
      bridge therapy for withdrawal headache, initiation of preventive medication, and
      close follow-up.

PMID- 16628535
TI  - Diagnosis and treatment of cluster headache.
AB  - Cluster headache is an uncommon yet distinctive neurovascular syndrome occurring
      in either episodic or chronic patterns. The most unique feature of cluster
      headache is the unmistakable circadian and circannual periodicity. The attacks
      are stereotypical, that is, of extreme intensity, of short duration, occurring
      unilaterally, and associated with robust signs and symptoms of autonomic
      dysfunction. Unlike migraine, during an attack the patient with cluster headache
      often paces about. Attacks frequently occur at night, awakening the patient from
      sleep. Although the pathophysiology of cluster headache remains to be fully
      elucidated, several seminal observations have recently been made. The medical
      treatment of cluster headache includes acute, transitional, and maintenance
      prophylaxis. Agents used for acute therapy include inhalation of oxygen and
      triptans, such as sumatriptan, and dihydroergotamine. Transitional prophylaxis
      refers to the short-term use of fast-acting agents. This typically involves
      either corticosteroids or ergotamine derivatives. The mainstay of prophylactic
      therapy is verapamil. Lithium, divalproex sodium, or topiramate may also be
      useful. As the sophistication of functional neuroimaging increases, so too will
      our ability to better understand the anatomic and metabolic perturbations that
      underlie cluster headache.

PMID- 16628536
TI  - Paroxysmal hemicrania, SUNCT, and hemicrania continua.
AB  - The trigeminal autonomic cephalalgias (TACs) are a group of primary headache
      disorders characterized by unilateral pain in the somatic distribution of the
      trigeminal nerve and ipsilateral autonomic signs, which reflect activation of the
      cranial parasympathetic pathway. The group includes cluster headache, paroxysmal
      hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival
      injection and tearing. Hemicrania continua was previously classified as one of
      the TACs. Despite their common elements, individually these headaches differ with
      respect to attack duration, frequency, and response to indomethacin.

PMID- 16628537
TI  - Latham and the vasomotor theory of migraine.

PMID- 16628538
TI  - Intensive extracorporeal photochemotherapy in pediatric patients with chronic
      graft-versus-host disease (cGVHD).
AB  - Extracorporeal photochemotherapy (ECP) is an alternative treatment approach in
      the management of chronic graft-versus-host disease (cGVHD). However, few reports
      have investigated the optimal treatment schedule of ECP. We treated seven
      pediatric patients with steroid-resistant or -dependent cGVHD with ECP. Using the
      Therakos UVAR XTS system, ECP was begun three (three patients) or five (four
      patients) times a week initially. Complete and partial responses were obtained in
      three patients. Three of seven patients died of GVHD-related complications. In
      this group initial intensive ECP did not improve the rate of response. However,
      this schedule appeared well tolerated.

PMID- 16628539
TI  - Half-numerical evaluation of pseudopotential integrals.
AB  - A half-numeric algorithm for the evaluation of effective core potential integrals
      over Cartesian Gaussian functions is described. Local and semilocal integrals are
      separated into two-dimensional angular and one-dimensional radial integrals. The
      angular integrals are evaluated analytically using a general approach that has no
      limitation for the l-quantum number. The radial integrals are calculated by an
      adaptive one-dimensional numerical quadrature. For the semilocal radial part a
      pretabulation scheme is used. This pretabulation simplifies the handling of
      radial integrals, makes their calculation much faster, and allows their easy
      reuse for different integrals within a given shell combination. The
      implementation of this new algorithm is described and its performance is
      analyzed.

PMID- 16628540
TI  - Metabolism of [14C]-2,4-dichlorophenol in edible plants.
AB  - Several 2,4-dichlorophenoxyacetic acid (2,4-D)-sensitive plants have been
      modified by genetic engineering with tfdA gene to acquire 2,4-D tolerance. The
      expression product of this gene degrades 2,4-D to 2,4-dichlorophenol (DCP), which
      is less phytotoxic but could cause a problem of food safety. After a comparison
      of 2,4-D and DCP metabolism in transgenic 2,4-D-tolerant and wild cotton
      (Gossypium hirsutum L.), a direct study of DCP metabolism in edible plants was
      performed. After petiolar uptake of a [U-phenyl-(14)C]-DCP solution followed by a
      48 h water chase, aqueous extracts were analysed by high-performance liquid
      chromatography. Metabolites were thereafter isolated and their structural
      identities were determined by enzymatic and chemical hydrolyses and mass
      spectrometry analyses. The metabolic fate of DCP was equivalent to 2,4-D
      metabolism in transgenic 2,4-D-tolerant cotton. In addition, DCP metabolism was
      similar in transgenic and wild cotton. The major terminal metabolites were DCP
      saccharide conjugates in all species, essentially DCP-(6-O-malonyl)-glucoside or
      its precursor DCP-glucose. The significance of this metabolic pathway with regard
      to food safety is discussed.

PMID- 16628541
TI  - An easy and rapid method using microscopy to determine herbicide effects in
      Poaceae weed species.
AB  - A new, easy, rapid and relatively inexpensive method using microscopy has been
      developed for the detection of herbicide effects in leaves of grass weed species
      displaying no visual signs of damage. The method has potential to be used as a
      tool to indicate future death of grass species due to herbicide exposure by
      observing phytochemical effects, i.e. early-warning effects. In the present
      study, Apera spica-venti (L.) Beauv., Bromus hordeaceus L., Alopecurus
      myosuroides Huds., Lolium perenne L. and Poa annua L. were exposed to lethal
      rates of four herbicides with different mode of action. The herbicides
      investigated were the thiocarbamate: prosulfocarb, the sulfonylurea:
      iodosulfuron, the aryloxyphenoxypropionate: fenoxaprop-P-ethyl and the
      organophosphate glyphosate. Autofluorescence of leaves was studied under a
      microscope using ultraviolet and blue light. The fluorescence of leaves treated
      to enhance flavonoids was also examined. To confirm the results,
      microspectrofluorometry was performed. Effects indicating future death of the
      grasses were observed in visually healthy leaves following treatment with
      prosulfocarb, glyphosate and iodosulfuron. No changes were detected following
      treatment with fenoxaprop-P-ethyl. After exposure to glyphosate or iodosulfuron,
      changes in the content of flavonoids and other compounds with a conjugation
      system and rigid structure and a decrease in the content of chlorophyll were
      detected in the leaves. Prosulfocarb treatment resulted in changes in the content
      of flavonoids and other compounds with a conjugation system and rigid structure
      and an increase in the content of chlorophyll in the leaves. The results obtained
      from microspectrofluorometry indicated that exposure to prosulfocarb caused a
      reduction in the flavonoids quercetin, naringenin and/or naringin.

PMID- 16628542
TI  - Fate of the herbicides glyphosate, glufosinate-ammonium, phenmedipham,
      ethofumesate and metamitron in two Finnish arable soils.
AB  - The fate of five herbicides (glyphosate, glufosinate-ammonium, phenmedipham,
      ethofumesate and metamitron) was studied in two Finnish sugar beet fields for 26
      months. Soil types were sandy loam and clay. Two different herbicide-tolerant
      sugar beet cultivars and three different herbicide application schedules were
      used. Meteorological data were collected throughout the study and soil properties
      were thoroughly analysed. An extensive data set of herbicide residue
      concentrations in soil was collected. Five different soil depths were sampled.
      The study was carried out using common Finnish agricultural practices and
      represents typical sugar beet cultivation conditions in Finland. The overall
      observed order of persistence was ethofumesate > glyphosate > phenmedipham >
      metamitron > glufosinate-ammonium. Only ethofumesate and glyphosate persisted
      until the subsequent spring. Seasonal variation in herbicide dissipation was very
      high and dissipation ceased almost completely during winter. During the 2 year
      experiment no indication of potential groundwater pollution risk was obtained,
      but herbicides may cause surface water pollution.

PMID- 16628543
TI  - Inhibition of nifedipine-induced proliferation of cultured human gingival
      fibroblasts by Saiko, a Chinese herbal medicine.
AB  - Saiko is predominantly contained in Saireito, a Chinese herbal medicine. The
      present study was conducted to determine whether or not Saiko is involved in the
      inhibition by Saireito of nifedipine-induced proliferation and collagen synthesis
      in gingival fibroblasts. Nifedipine (10 microM) significantly enhanced the
      proliferation starting on day 5 of the culture period. When added together with
      nifedipine, Saiko at concentrations of 0.05%-0.2% (w/v) dose-dependently
      inhibited the nifedipine-induced proliferation, and at the highest concentration
      tested (0.2%), Saiko inhibited the nifedipine-induced proliferation by about 40%.
      Moreover, Saiko (0.2%) also inhibited the normal proliferation at days 11 and 14.
      Sole application of nifedipine (10 microM) augmented the release of bFGF, and
      Saiko concentration-dependently reduced the level of bFGF in the nifedipine
      containing culture medium. Nifedipine (10 microM) increased the production of
      type I collagen to almost twice that of the control (normal medium), and Saiko at
      concentrations above 0.1% significantly reduced the nifedipineinduced production
      of collagen. In conclusion, the present findings demonstrate that Saiko inhibited
      the nifedipine-induced proliferation of gingival fibroblasts by reducing the
      release of bFGF and that Saiko is involved in the Saireito-induced inhibition of
      nifedipine-stimulated proliferation and collagen synthesis in gingival
      fibroblasts.

PMID- 16628544
TI  - A review of the bioactivity and potential health benefits of chamomile tea
      (Matricaria recutita L.).
AB  - Chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla)
      is one of the most popular single ingredient herbal teas, or tisanes. Chamomile
      tea, brewed from dried flower heads, has been used traditionally for medicinal
      purposes. Evidence-based information regarding the bioactivity of this herb is
      presented. The main constituents of the flowers include several phenolic
      compounds, primarily the flavonoids apigenin, quercetin, patuletin, luteolin and
      their glucosides. The principal components of the essential oil extracted from
      the flowers are the terpenoids alpha-bisabolol and its oxides and azulenes,
      including chamazulene. Chamomile has moderate antioxidant and antimicrobial
      activities, and significant antiplatelet activity in vitro. Animal model studies
      indicate potent antiinflammatory action, some antimutagenic and cholesterol
      lowering activities, as well as antispasmotic and anxiolytic effects. However,
      human studies are limited, and clinical trials examining the purported sedative
      properties of chamomile tea are absent. Adverse reactions to chamomile, consumed
      as a tisane or applied topically, have been reported among those with allergies
      to other plants in the daisy family, i.e. Asteraceae or Compositae.

PMID- 16628547
TI  - Estimates of the cancer burden in Europe from radioactive fallout from the
      Chernobyl accident.
AB  - The Chernobyl accident, which occurred April 26, 1986, resulted in a large
      release of radionuclides, which were deposited over a very wide area,
      particularly in Europe. Although an increased risk of thyroid cancer in exposed
      children has been clearly demonstrated in the most contaminated regions, the
      impact of the accident on the risk of other cancers as well as elsewhere in
      Europe is less clear. The objective of the present study was to evaluate the
      human cancer burden in Europe as a whole from radioactive fallout from the
      accident. Average country- and region-specific whole-body and thyroid doses from
      Chernobyl were estimated using new dosimetric models and radiological data.
      Numbers of cancer cases and deaths possibly attributable to radiation from
      Chernobyl were estimated, applying state-of-the-art risk models derived from
      studies of other irradiated populations. Simultaneously, trends in cancer
      incidence and mortality were examined over time and by dose level. The risk
      projections suggest that by now Chernobyl may have caused about 1,000 cases of
      thyroid cancer and 4,000 cases of other cancers in Europe, representing about
      0.01% of all incident cancers since the accident. Models predict that by 2065
      about 16,000 (95% UI 3,400-72,000) cases of thyroid cancer and 25,000 (95% UI
      11,000-59,000) cases of other cancers may be expected due to radiation from the
      accident, whereas several hundred million cancer cases are expected from other
      causes. Although these estimates are subject to considerable uncertainty, they
      provide an indication of the order of magnitude of the possible impact of the
      Chernobyl accident. It is unlikely that the cancer burden from the largest
      radiological accident to date could be detected by monitoring national cancer
      statistics. Indeed, results of analyses of time trends in cancer incidence and
      mortality in Europe do not, at present, indicate any increase in cancer rates --
      other than of thyroid cancer in the most contaminated regions -- that can be
      clearly attributed to radiation from the Chernobyl accident.

PMID- 16628548
TI  - Determination of strength and deformation behavior of human cartilage for the
      definition of significant parameters.
AB  - In reconstructive surgery, an artificial supporting scaffold made from autogenous
      cartilage from the rib, the ear concha, or the nasal septum is used as a
      substitute for the destroyed endogenous tissue in the ear concha, the nose, the
      trachea, and in parts of the facial skeleton. For the successful use of polymer
      materials in reconstructive surgery, an exact knowledge of the material
      properties of the natural tissues is required. The applicability of conventional
      material test methods was examined with regard to the suitability of the test
      methodology. Materials properties are to be assessed for different specimen sizes
      and geometries. Human cartilage specimens from the septum, rib, and ear were
      subsected to the following test methods: (1) tension, (2) bending, (3)
      compression, and (4) micro-hardness measuring. Specimen geometry was evaluated
      for each experimental method by taking into account the dimensions of samples
      used in plastics testing as well as the appropriate model of miniaturization.
      Elastic properties determined using test methods (1), (2), and (3) are Et
      sep=(7.2+/-3.4) MPa, Ef-rib=(8.8+/-2.9) MPa, and Ec-rib=(103+/-30) MPa. The micro
      hardness values hpl fluctuate for septum from 1 to 4 N/mm2 and for the rib from
      0.5 to 1.3 N/mm2. The experiments have shown that, beside the sex- and age
      specific values recorded, the standard values and their variation are
      particularly influenced by preparation technique and by the conditions of
      storage. As a result of these first investigations, characteristic values for
      strength and deformation were determined under quasistatic and dynamic load
      conditions. The aim of this study was not the determination of statistically
      firmed properties, but the examination of the applicability of mechanical test
      methods of the polymer testing for these materials.

PMID- 16628549
TI  - Does seeding density affect in vitro mineral nodules formation in novel composite
      scaffolds?
AB  - This study investigated the human alveolar osteoblasts (AOs) proliferation and
      extracellular matrix formation at seeding density of 0.05, 0.1, 0.2, 0.4, and 0.8
      million (M) per 3x4x4 mm3 on medical grade polycaprolactone-tricalcium phosphate
      (mPCL-TCP) scaffolds designed for bone regeneration. Over 80-90% of the initial
      seeded cells were retained in the scaffolds after 24 h. AOs bridged over pores at
      density of 0.2M/scaffold and below, but formed cell balls at density of
      0.4M/scaffold and above. At seeding density of 0.2M and below, cell proliferation
      increased with time having DNA content peaked to 1600 ng/scaffold at day 21 and
      28, respectively, whereas at 0.4 and 0.8M, the corresponding DNA content
      decreased to 1600 ng in 28 days. At day 7, higher alkaline phosphatase (ALP)
      activity and higher osteocalcin (OCN) secretion were detected at 0.2M/scaffold
      and below. After 28 days, multilayered cell-sheet formation and collagen fibers
      were observed at all densities. ALP and OCN in matrix and mineral nodules were
      found mainly at the border of AOs-scaffold construct. These findings demonstrated
      that the density of 0.2M and below per 3 x 4 x 4 mm(3) scaffold resulted in
      better cell proliferation and extracellular matrix synthesis, potentially
      resulting in better mineralized tissue formation.

PMID- 16628550
TI  - A method for the effective formation of hepatocyte spheroids using a
      biodegradable polymer nanosphere.
AB  - Cultures of hepatocytes in spheroid form are known to maintain higher cell
      viability and exhibit better hepatocyte functions than those in monolayer
      cultures. In this study, a method for the formation of hepatocyte spheroids was
      developed using biodegradable polymer nanospheres. The addition of poly(lactic-co
      glycolic acid) nanospheres to hepatocyte cultures in spinner flasks increased the
      efficiency of hepatocyte spheroid formation (the number of cells in spheroids
      divided by the total cell number) as compared with hepatocyte cultures without
      nanospheres (control). The viability and mitochondrial activity of the hepatocyte
      spheroids in the nanosphere-added cultures were significantly higher than those
      in the control. In addition, the mRNA expression levels of albumin and
      phenylalanine hydroxylase, both of which are hepatocyte-specific proteins, were
      significantly higher in the nanosphere-added cultures than in the control. This
      new culture method improves upon the conventional method of forming hepatocyte
      spheroids in terms of spheroid formation efficiency, cell viability, and
      hepatocyte function.

PMID- 16628551
TI  - Avian pancreatic polypeptide fragments refold to native aPP conformation when
      combined in solution: a CD and VCD study.
AB  - An equimolar mixture of avian pancreatic polypeptide (aPP) fragments aPP(1-11)
      NH2 and Ac-aPP(12-36) had an electronic circular dichroism (ECD) spectrum that
      was similar to that of whole aPP in H2O and even more so in 30% (v/v)
      trifluoroethanol (TFE) in 15 mM Na2HPO4, but was different from the sum of the
      spectra of the individual fragments. The vibrational circular dichroism (VCD)
      spectrum of the combined fragments in 30% (v/v) TFE in 15 mM Na2HPO4 in D2O was
      also similar to that of the intact aPP and unlike the sum of the VCD spectra of
      the fragments. The interaction of these fragments is thus sufficient to support
      the conformation of whole aPP. This study demonstrates that VCD, in combination
      with ECD, is useful for the study of protein-protein interactions.

PMID- 16628552
TI  - Ifosfamide-induced nephrotoxicity in 593 sarcoma patients: a report from the Late
      Effects Surveillance System.
AB  - BACKGROUND: Ifosfamide is widely used in paediatric oncology, but its use is
      limited by nephrotoxic side effects. The aim of this study was to evaluate the
      incidence and risk factors of tubulopathy, with special emphasis on the influence
      of age, where different findings have been published so far. PROCEDURE: Five
      hundred ninety three children and adolescents treated for Ewing, osteo- or soft
      tissue sarcoma (median age at diagnosis: 11.7 years) were prospectively
      investigated for nephrotoxicity in the Late Effects Surveillance System (LESS)
      study. Tubulopathy was diagnosed in case of continuing hypophosphatemia and
      proteinuria. RESULTS: After a median follow up of 19 months, 27 patients (4.6%;
      95% CI: 3.0-6.6%) had newly developed tubulopathy. This incidence was 0.4% (95%
      CI: 0-2.4%) in patients treated with a cumulative ifosfamide dose of < or =24
      g/m2, 6.5% (95% CI: 3.6-10.7%) after 24-60 g/m2, and 8.0% (95% CI: 4.2-13.6%)
      after > or = 60 g/m2. In multivariate analysis, children younger than 4 years at
      time of diagnosis had an 8.7-fold (95% CI: 3.5-21.8) higher risk for tubulopathy
      than older patients. Neither carboplatin treatment nor abdominal irradiation
      showed any significant influence. CONCLUSION: Ifosfamide-induced nephrotoxicity
      was found in 4.6% of patients. Risk factors were the cumulative ifosfamide dose
      and young age at treatment.

PMID- 16628553
TI  - Assessment of health-related quality of life of adolescent cancer patients using
      the Minneapolis-Manchester Quality of Life Adolescent Questionnaire.
AB  - BACKGROUND: Improved survival after childhood cancer has shifted the focus to
      health-related quality of life (HRQL)-an understudied problem, especially among
      adolescents. PROCEDURE: We assessed HRQL among adolescents utilizing a validated
      self-report tool, the Minneapolis-Manchester Quality of Life (MMQL) Adolescent
      Form, consisting of 46 items comprising seven domains: physical, cognitive,
      psychological and social functioning, body image, intimate relations, and outlook
      on life, and computed an overall QoL score. The MMQL Adolescent Form was
      administered to 226 adolescent survivors of childhood cancer a median of 7.8
      years from diagnosis (off therapy-median age: 16.2 years), 136 adolescent cancer
      patients undergoing therapy (on therapy-median age: 16.4 years), and 134 healthy
      adolescents (controls-median age: 15.5 years). Primary diagnoses included
      leukemia (46%), lymphoma (26%), brain tumors (5%), and other solid tumors (23%).
      RESULTS: Compared to healthy controls, on-therapy patients were at increased risk
      for reporting poor overall QoL [Odds Ratio (OR) = 3.3, P = 0.002)] and poor
      physical functioning (OR = 11.8, P < 0.001). Off-therapy survivors did not differ
      significantly from healthy controls for overall QoL (OR = 1.6, P = 0.5) or any
      HRQL domains. Female patients, both on- and off-therapy, were more likely to
      report poorer overall QoL, physical, psychological and cognitive functioning as
      well as poorer body image when compared with male patients. CONCLUSIONS: While
      adolescent cancer patients undergoing active therapy report poor physical
      functioning, there is no evidence of long-term QoL sequelae.

PMID- 16628554
TI  - Childhood essential thrombocytosis.

PMID- 16628555
TI  - Allogeneic bone marrow transplantation with reduced intensity conditioning for
      chronic granulomatous disease complicated by invasive Aspergillus infection.
AB  - Chronic granulomatous disease (CGD) is a rare disorder characterized by recurrent
      infections, often resulting in impaired quality of life and death. Allogeneic BMT
      provides a definitive cure for CGD, but carries a significant risk of mortality
      and morbidity. The risk is higher for those who have invasive fungal infection
      prior to transplant. Reduced intensity conditioning (RIC) is associated with less
      toxicity from the conditioning agents and may provide an alternative option for
      all non-malignant diseases. We report a case of successful allogeneic BMT after
      RIC for a case of X-linked CGD complicated by severe invasive aspergillosis (IA).

PMID- 16628556
TI  - Validation of the oral mucositis assessment scale in pediatric cancer.
AB  - BACKGROUND: Our objective was to examine the construct validity of the Oral
      Mucositis Assessment Scale (OMAS) in children receiving doxorubicin chemotherapy.
      METHODS: Children between 6 and 18 years of age with cancer receiving doxorubicin
      containing chemotherapy were included. OMAS was measured on days 7, 10, 14, and
      17 after chemotherapy. Other measures of mucositis obtained concurrent with OMAS
      were the World Health Organization (WHO) mucositis scale and pain visual analogue
      scale (VAS). We also recorded analgesia administration. RESULTS: Sixteen children
      were studied for 45 post-chemotherapy cycles and 156 OMAS assessments were
      performed. OMAS was moderately correlated with WHO scores (r = 0.56; P = 0.0006)
      whereas correlation with the pain VAS was fair (r = 0.37; P = 0.002). OMAS also
      had fair correlation with the number of doses of topical analgesia (r = 0.43; P =
      0.001) and with the cumulative dose of opioid analgesia (r = 0.38; P = 0.003).
      CONCLUSIONS: The OMAS is valid for use in mucositis clinical trials for children
      at least 6 years of age.

PMID- 16628557
TI  - Neuroblastoma in adults: Incidence and survival analysis based on SEER data.
AB  - PURPOSE: Clinical data on survival outcomes of adult patients (defined as 20
      years of age and older) with neuroblastoma are scarce due to the rarity of the
      disease. Small single institution reports have described worse outcomes for
      adults than pediatric patients. MATERIALS/METHODS: Data from the public access
      Surveillance Epidemiology and End Results database were reviewed for a 30-year
      period between 1973 and 2002 for the diagnosis of neuroblastoma. Analyses
      compared frequency and survival rates of neuroblastoma among children and adults
      with particular focus on the incidence, case characteristics, and long-term
      survival of the adult patients. RESULTS: The observed 3- and 5-year survival
      rates were lowest among adult patients (45.9% and 36.3%, respectively), whereas
      infants fared best with 86.0% 3-year and 84.6% 5-year overall survival. There was
      a steady decline in the incidence of adult neuroblastoma from 0.47 cases per
      million per year in 1973-1977 to 0.12 cases per million per year in 1998-2002.
      When the long-term adult neuroblastoma survival was examined in detail for 1-, 3
      , 5-, 7-, and 10-year follow-up periods, there was continuous decrease in
      survival during the first 7 years after the diagnosis with subsequent
      stabilization for both observed (OS) and relative survival (RS) rates. There was
      a notable trend towards improved outcome over the past three decades.
      CONCLUSIONS: Adults with neuroblastoma have significantly worse outcome than
      children. This may be due to tumor biology, more virulent clinical course, or
      possibly due to the fact that adults are less sensitive or have poor tolerance to
      pediatric chemotherapy regimens.

PMID- 16628558
TI  - A meta-analysis of the neurocognitive sequelae of treatment for childhood acute
      lymphocytic leukemia.
AB  - BACKGROUND: Impaired neurocognitive functioning is one increasingly recognized
      long-term consequence of childhood ALL treatment. However, research findings have
      been inconsistent regarding the domains affected and the degree to which they are
      compromised. PROCEDURE: A comprehensive meta-analytic review of the long-term
      neurocognitive effects of childhood ALL was conducted. Studies were included if
      they were published in English, reported original quantitative data on the post
      treatment neurocognitive functioning of childhood ALL patients in first remission
      and control groups, and used neurocognitive measures with adequate psychometric
      properties and published normative data. RESULTS: Data from 28 empirical studies
      yielding 13 effect sizes across nine domains were extracted and analyzed. All
      effects were negative (g = -0.34 to -0.71), demonstrating that ALL survivors
      consistently experienced significant deficits in intellectual functioning,
      academic achievement, and specific neurocognitive abilities compared to control
      groups. The role of potential moderators, including treatment with cranial
      irradiation, age at time of diagnosis, and time since treatment ended, was
      examined. However, no effects emerged as clearly and consistently moderated by
      these variables. CONCLUSIONS: The results from this meta-analysis suggest that
      declines in both global and specific areas of areas of neurocognitive functioning
      occur as a result of contemporary ALL treatment. Such deficits have significant
      implications for survivors' academic achievement and overall quality of life.
      Neurocognitive assessment plays a critical role in determining what remedial or
      specialized instruction is needed in childhood ALL survivors and should be
      included as a standard part of long-term follow-up care.

PMID- 16628559
TI  - A centralized approach to tandem mass spectrometry method development for high
      throughput ADME screening.
AB  - A centralized approach to acquisition and dissemination of tandem mass
      spectrometry (MS/MS) conditions within an ADME-screening bioanalytical mass
      spectrometry group has been developed. The method development process uses two
      automated software products (Autoscan and Automaton) specifically designed for
      mass spectrometers manufactured by MDS Sciex. Both provide the ability to quickly
      determine selected reaction monitoring (SRM) transitions for hundreds of
      compounds per day. In addition, Autoscan determines optimal polarity and
      collision energy (CE). Automaton also determines the optimal declustering
      potential (DP) as well as the CE. The resulting optimized conditions are loaded
      into a central database for access by LC/MS/MS bioanalysis workstations in the
      group. The effect of DP and CE on the sensitivity was investigated. Optimization
      of DP improved signal response about 27% on average. For approximately 10% of
      compounds, signal enhancement was greater than 50% compared to the generic
      setting. A generic setting of DP = 25 V can be used for the majority of ADME
      screening applications. Optimization of CE can have a much larger impact on
      signal intensity and a minimum of three CE settings should be tested. We have
      determined that CE values of 1, 30 and 45 V provide adequate coverage for most
      small molecule drug discovery analytes.

PMID- 16628560
TI  - Ion sampling effects under conditions of total solvent consumption.
AB  - The motivation of this work was to study some of the properties of
      nanoelectrospray operation under conditions where the entire sprayed liquid is
      vaporized and inhaled into the vacuum system. Under these conditions the
      desolvation requirements, sampling efficiency, concentration versus mass
      sensitivity, and molar response characteristics of various compounds were
      studied. The combined efficiency of ion production from solution and transfer
      into the vacuum system, referred to as sampling efficiency, is presented under
      various inlet conditions including different flow rates, solution compositions,
      and compound types. Under ideal solvent conditions the results for favorable
      compounds show sampling efficiencies of 70-85% at flows in the range of 50-500
      nL/min. Efficiencies were lower for aqueous samples and compounds of different
      structures gave different molar response factors under these high sampling
      efficiency conditions. The relative molar response factors are presented in terms
      of those observed with higher flow rate sources which operate at significantly
      lower sampling efficiencies. In all cases, operating in this flow regime, the ion
      count rate was directly proportional to the absolute mass of analyte molecules
      entering the source. The experimental source used to carry out these studies
      included gas nebulization to stabilize the electrospray process, a heated laminar
      flow chamber to enhance desolvation and ion production, and various atmosphere-to
      vacuum aperture diameters to maximize ion transfer.

PMID- 16628561
TI  - The influence of structural features on facile McLafferty-type, even-electron
      rearrangements in tandem mass spectra of carboxylate anions.
AB  - In contrast to the well-described McLafferty rearrangement in odd-electron
      cations, relatively little has been reported on comparable rearrangements in even
      electron ions, especially negative ions. This work reports a systematic study
      using tandem mass spectrometry (MS/MS) fragment ion spectra of carboxylate anions
      having a suitably acidic proton in the gamma position. The rearrangement process
      was studied in both ion trap and triple quadrupole mass spectrometers;
      characteristic enolate anions and stable neutral products were formed at low
      collision energies. The process has diagnostic and analytical potential in, for
      example, the analysis of peptides having C-terminal serine residues and of 3
      hydroxy- or 3-aminocarboxylic acids in complex mixtures.

PMID- 16628562
TI  - Analysis of the stochastic variation in LTQ single scan mass spectra.
AB  - A better understanding of the scan-to-scan signal intensity variation can lead to
      more sophisticated algorithms for database searching and de novo peptide
      sequencing using single scan mass spectra. In this study, we systematically
      studied the variation in relative intensity of m/z values in the single scan
      product ion mass spectra (MS2) derived from five representative precursor ions
      (MS1) collected using an LTQ linear ion trap under constant flow direct infusion
      conditions with peptide concentrations held constant. We applied a matching
      algorithm based on a pair hidden Markov model to align the peaks from each scan
      belonging to the same m/z value prior to assessing the signal intensity
      variation. The most significant single contributor to scan-to-scan signal
      intensity variation for high abundance ions was centroider error. Our study also
      showed that the variation in signal intensity is higher than what would be
      expected if the ion statistics derived from the dual geometry electron multiplier
      detector followed a Poisson distribution.

PMID- 16628563
TI  - Study of automated mass spectral deconvolution and identification system (AMDIS)
      in pesticide residue analysis.
AB  - The effects of overlapping levels and concentration ratios of overlapping
      components, and of scan rates of the mass spectrometer, on the capability of the
      automated mass spectral deconvolution and identification system (AMDIS) in
      pesticide residue analysis were studied. To investigate the capability of AMDIS
      in removing interferences from the overlapping peaks, this system was applied to
      data files obtained from the gas chromatography/mass spectrometry (GC/MS)
      analysis of two overlapping (co-eluting) pesticides (beta-HCH and PCNB) in full
      scan mode. Differences in overlap levels, the concentration ratios of the two
      overlapping components and the scan rates of the instrument were studied. When
      the difference in scan number of overlapping compounds was equal to 1 scan, AMDIS
      incompletely extracted 'purified' mass spectra but as the difference increased to
      3 or more scans, complete correct spectra could be extracted. The results also
      show that when the scan rate was in the range of 0.4-0.90 s/scan and the
      concentration ratios of the target compound/interference were above 1/5, there
      were ideal deconvolution results for this approach. To further study the
      application of AMDIS to pesticide residue analysis, AMDIS was applied to the
      identification of pesticides spiked in real samples (cabbage and rice). Typical
      pesticides being evaluated were identified using AMDIS at concentrations >50 ng/g
      in the extracts.

PMID- 16628564
TI  - Serial analysis of stable nitrogen and carbon isotopes in hair: monitoring
      starvation and recovery phases of patients suffering from anorexia nervosa.
AB  - Stable nitrogen and carbon isotopic ratios of hair strands of six patients
      suffering from anorexia nervosa were measured to monitor a dietary change from
      near starvation to recovery. This paper presents the results of a first-time
      study of nitrogen and carbon balance of the patients prior to and after
      admittance to a hospital and therapy. Sequential analysis of the isotopic ratios
      of hair strands of all patients could be related to the respective body mass
      index (BMI) of each patient. Our hypothesis concerning the diachronic change in
      delta15N and delta13C during therapy was met: The delta15N values were inversely
      related to the BMI, indicating a slow-down in catabolism of bodily protein due to
      the process of gluconeogenesis during the starvation phase. In contrast, the
      delta13C values and BMI were in phase: an increase in BMI resulted in an increase
      in the delta13C values. This rise in delta13C ratios is best interpreted by an
      increased supply of protein in the diet. Furthermore, delta15N and delta13C were
      inversely related. We conclude that hair, which is easily and non-traumatically
      sampled, is an adequate monitor that reflects dietary change and nitrogen balance
      within days. This isotopic method may also be applied in forensic studies with
      regard to cases of deprivation, and starvation, and may be a method for
      investigating starvation in historic populations.

PMID- 16628565
TI  - Photocatalytic degradation of phenyl-urea herbicides chlortoluron and
      chloroxuron: characterization of the by-products by liquid chromatography coupled
      to electrospray ionization tandem mass spectrometry.
AB  - The first stages of the photocatalytic degradation of the compounds chlortoluron
      [3-(3-chloro-4-methylphenyl)-1,1-dimethylurea] and chloroxuron [3-[4-(4
      chlorophenoxy)phenyl]-1,1-dimethylurea], belonging to the class of phenyl-urea
      herbicides, were investigated using high-performance liquid chromatography (HPLC)
      coupled to electrospray ionization ion trap tandem mass spectrometry (ESI-IT
      MS/MS). Degradation was accomplished under solar radiation, using TiO2 embedded
      into a polyvinylidene fluoride (PVDF) transparent matrix as a heterogeneous
      photocatalyst. Aliquots of the chlorinated herbicide solutions were withdrawn at
      different times and subjected to gradient elution, reversed-phase HPLC
      separations, specifically optimized to obtain the highest resolution between
      peaks related to the herbicide degradation by-products. The latter were then
      investigated using MS detection; in particular, MS/MS measurements were made and
      structural information was obtained from the interpretation of fragmentation
      data. Several by-products were identified; the most important ones are
      hydroxylated compounds arising from the interaction between the two chlorinated
      herbicides and OH radicals generated at the TiO2 surface under irradiation. Other
      by-products were generated by slightly different processes, namely demethylation,
      dearylation and dechlorination, eventually followed by interaction with OH
      radicals.

PMID- 16628566
TI  - Dedication to Bob Boyd.

PMID- 16628567
TI  - Assessing the properties of internal standards for quantitative matrix-assisted
      laser desorption/ionization mass spectrometry of small molecules.
AB  - Growing interest in the ability to conduct quantitative assays for small
      molecules by matrix-assisted laser desorption/ionization (MALDI) has been the
      driving force for several recent studies. This present work includes the
      investigation of internal standards for these analyses using a high-repetition
      rate MALDI triple quadrupole instrument. Certain physicochemical properties are
      assessed for predicting possible matches for internal standards for different
      small molecules. The importance of similar molecular weight of an internal
      standard to its analyte is seen through experiments with a series of
      acylcarnitines, having a fixed charge site and growing alkyl chain length. Both
      acetyl- and hexanoyl-carnitine were systematically assessed with several other
      acylcarnitine compounds as internal standards. The results clearly demonstrate
      that closely matched molecular weights between analyte and internal standard are
      essential for acceptable quantitation results. Using alpha-cyano-4
      hydroxycinnamic acid as the organic matrix, the similarities between analyte and
      internal standard remain the most important parameter and not necessarily their
      even distribution within the solid sample spot. Several 4-quinolone antibiotics
      as well as a diverse group of pharmaceutical drugs were tested as internal
      standards for the 4-quinolone, ciprofloxacin. Quantitative results were shown
      using the solution-phase properties, log D and pKa, of these molecules. Their
      distribution coefficients, log D, are demonstrated as a fundamental parameter for
      similar crystallization patterns of analyte and internal standard. In the end, it
      was also possible to quantify ciprofloxacin using a drug from a different
      compound class, namely quinidine, having a similar log D value as the analyte.

PMID- 16628568
TI  - Combining protein identification and quantification: C-terminal isotope-coded
      tagging using sulfanilic acid.
AB  - Two methods of differential isotopic coding of carboxylic groups have been
      developed to date. The first approach uses d0- or d3-methanol to convert carboxyl
      groups into the corresponding methyl esters. The second relies on the
      incorporation of two 18O atoms into the C-terminal carboxylic group during
      tryptic digestion of proteins in H(2)18O. However, both methods have limitations
      such as chromatographic separation of 1H and 2H derivatives or overlap of
      isotopic distributions of light and heavy forms due to small mass shifts. Here we
      present a new tagging approach based on the specific incorporation of sulfanilic
      acid into carboxylic groups. The reagent was synthesized in a heavy form (13C
      phenyl ring), showing no chromatographic shift and an optimal isotopic separation
      with a 6 Da mass shift. Moreover, sulfanilic acid allows for simplified
      fragmentation in matrix-assisted laser desorption/ionization (MALDI) due the
      charge fixation of the sulfonate group at the C-terminus of the peptide. The
      derivatization is simple, specific and minimizes the number of sample treatment
      steps that can strongly alter the sample composition. The quantification is
      reproducible within an order of magnitude and can be analyzed either by
      electrospray ionization (ESI) or MALDI. Finally, the method is able to
      specifically identify the C-terminal peptide of a protein by using GluC as the
      proteolytic enzyme.

PMID- 16628569
TI  - Simultaneous analysis of prostanoids using liquid chromatography/high-field
      asymmetric waveform ion mobility spectrometry/tandem mass spectrometry.
AB  - A liquid chromatography/high-field asymmetric waveform ion mobility
      spectrometry/tandem mass spectrometry (LC-FAIMS-MS/MS) semi-quantitative method
      was developed for the simultaneous determination of prostaglandin (PG) E2, PGD2,
      PGF(2alpha), 6-keto-PGF(1alpha), and thromboxane (TX) B2. Diluted samples
      containing these prostanoids and their tetra-deuterium-substituted internal
      standards were analyzed by LC followed by either selected reaction monitoring (LC
      SRM) or FAIMS and selected reaction monitoring (LC-FRM). FAIMS reduced background
      noise, separated the isobaric ions PGE2 and PGD2, and separated dynamically
      interchanging TXB2 anomers. This is the first report of the separation of
      interconverting anomers by FAIMS. Generally, the LC-FRM chromatograms were more
      selective than the LC-SRM chromatograms. Its potential was demonstrated by
      analysis of prostanoids in guinea pig lumbar spinal cord homogenate.

PMID- 16628570
TI  - Improved cell typing by charge-state deconvolution of matrix-assisted laser
      desorption/ionization mass spectra.
AB  - Robust, specific, and rapid identification of toxic strains of bacteria and
      viruses, to guide the mitigation of their adverse health effects and optimum
      implementation of other response actions, remains a major analytical challenge.
      This need has driven the development of methods for classification of
      microorganisms using mass spectrometry, particularly matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS), that allows high-throughput
      analyses with minimum sample preparation. We describe a novel approach to cell
      typing based on pattern recognition of MALDI mass spectra, which involves charge
      state deconvolution in conjunction with a new correlation analysis procedure. The
      method is applicable to both prokaryotic and eukaryotic cells. Charge-state
      deconvolution improves the quantitative reproducibility of spectra because
      multiply charged ions resulting from the same biomarker attaching a different
      number of protons are recognized and their abundances are combined. This allows a
      clearer distinction of bacterial strains or of cancerous and normal liver cells.
      Improved class distinction provided by charge-state deconvolution was
      demonstrated by cluster spacing on canonical variate score charts and by
      correlation analyses. Deconvolution may enhance detection of early disease state
      or therapy progress markers in various tissues analyzed by MALDI-MS.

PMID- 16628571
TI  - Correlations between synthetic peptide-based enzyme immunoassays and
      immunofluorescence assay for detection of human herpesvirus 8 antibodies in
      different Argentine populations.
AB  - Human herpesvirus 8 (HHV-8) antibody tests vary in sensitivity and specificity,
      depending on the population tested and on the type of assay. In this study, we
      evaluated the sensitivity and specificity of two peptide enzyme immunoassays
      using a multiple antigenic peptide (PK8.1-MAP) or a chimeric peptide (PK8.1
      orf65) as the antigens and determined the HHV-8 seroprevalence in different
      Argentine populations using an immunofluorescence assay (IFA) as reference. For
      analysis, when either or both of the peptide EIAs were positive, the specimen was
      considered positive (PEIA). We estimated the sensitivity and specificity of PEIA
      to be 97% using Kaposi's sarcoma (KS) patients and healthy individuals as
      positive and negative controls respectively. Then, we expanded the control groups
      to include IFA positive men who have sex with men (MSM) and IFA negative blood
      donors. The sensitivity decreased to 83% but specificity remained high at 98%.
      Concordance between PEIA and IFA was 77% for 1/40 IFA titers and increased to 90%
      for titers >or=1/160. Seroprevalences for HHV-8 performed in the HIV positive MSM
      were (IFA 73.1%; PEIA55.2%); heterosexuals (52.5%, 22.2%), which includes
      injecting drug users (IDU) (54.0%, 32.4%) and non-IDU (51.6%, 16.1%). The
      inclusion of non-KS HHV-8 IFA positive individuals to the positive controls may
      be a substantial improvement towards the realistic assessment of assay
      sensitivity. These peptide EIAs can be used for trends in populations with high
      probability of being HHV-8 infected and negative results should be confirmed by
      IFA. IFA test is still the most suitable test for populations with low
      probabilities of being infected.

PMID- 16628572
TI  - Fecal cytokines and markers of intestinal inflammation in international travelers
      with diarrhea due to Noroviruses.
AB  - The intestinal immune and inflammatory responses of Norovirus (NoV) are poorly
      defined. The objective of this study was to investigate fecal cytokine and
      lactoferrin profiles in response to NoV gastroenteritis in travelers. Both fecal
      cytokines and fecal lactoferrin were measured for NoV-associated diarrhea (N =
      7), mixed infection of NoV and enterotoxigenic E. coli (ETEC)-associated diarrhea
      (N = 10) and in pathogen-negative diarrhea cases (N = 19). Both IL-2 and IFN
      gamma were significantly increased in NoV-associated diarrhea specimens,
      suggesting a predominant Th1 immune response to NoV infection in the gut. When a
      mixed infection of NoV and ETEC occurred, a combined Th1/Th2 response was
      observed suggesting a dual immune response secondary to infection by both
      pathogens. Intestinal inflammation associated with increased fecal lactoferrin,
      important in bacterial enteric infection, was not found in NoV-associated
      gastroenteritis.

PMID- 16628573
TI  - Network of sexual contacts and sexually transmitted HIV infection in Burkina
      Faso.
AB  - Two thirds of the people who have been infected by human immunodeficiency virus
      (HIV) in the world live in Sub-Saharan African countries. The results of a study
      measuring the degree distribution of the network of sexual contacts in Burkina
      Faso are described. Such a network is responsible for the spread of sexually
      transmitted diseases, and in particular of HIV. It has been found that the number
      of different sexual partners reported by males is a power law distribution with
      an exponent gamma = 2.9 (0.1). This is consistent with the degree distribution of
      scale-free networks. On the other hand, the females can be divided into two
      groups: the prostitutes with an average of 400 different partners per year, and
      females with a stable partner, having a rapidly decreasing degree distribution.
      Such a result may have important implications on the control of sexually
      transmitted diseases and in particular of HIV. Since scale-free networks have no
      epidemic threshold, a campaign based on prevention and anti-viral treatment of
      few highly connected nodes can be more successful than any policy based on
      enlarged but random distribution of the available anti-viral treatments.

PMID- 16628574
TI  - Correlates of placental infection with cytomegalovirus, parvovirus B19 or human
      herpes virus 7.
AB  - Vertical transmission of viruses is an important cause of morbidity in the fetus
      and neonate. Placental viral infection indicates risk of vertical transmission,
      but not always transmission to, or disease of the fetus. Specimens from mothers
      and babies from three groups-two prospective and one retrospective cohort-were
      tested for pathogens of teratogenic potential using multiplex PCR. Placental
      infection was present in 13% of the 105 samples collected. Assessment of the
      prospective cohorts showed cytomegalovirus (CMV) detected in 4% of placentae from
      unselected women, parvovirus B19 in 1% and Ureaplasma parvum in 1% of placentae.
      In a retrospective cohort of women at high risk of transmitting congenital
      infection due to seroconversion during pregnancy, miscarriage or stillbirth, CMV
      was detected in 64% and human herpes virus type 7 in 9% of placentae. Of 14 PCR
      positive placentae, two were associated with the birth of a living symptomatic
      infant, two with stillbirth, one with miscarriage, and two with elective
      terminations of pregnancy. Directed laboratory assessment of women at high risk
      of transmitting congenital infection, on the basis of clinical or laboratory
      markers, is important for accurate diagnosis of adverse outcomes of pregnancy.
      However, routine screening for viruses in the placentae from women with a low
      risk serological profile for transmitting congenital infection is unlikely to
      result in significant numbers of additional diagnoses and is confounded by
      inadequacy of current diagnostic methods. The major pathogen detected in all
      cases of placental infection associated with fetal death was human CMV.

PMID- 16628575
TI  - Trends in drug resistance mutations in antiretroviral-naive intravenous drug
      users of Rio de Janeiro.
AB  - DNA sequencing of a pol gene fragment from drug-naive injecting drug users
      samples obtained at two time points of the Brazilian AIDS epidemic (Pre-HAART
      era: 1994 to early 1997, n = 27; post-HAART era: 1999-2001, n = 38) was
      undertaken to assess HIV-1 antiretroviral drug resistance mutations and subtyping
      profiles. Genotypic analysis revealed the presence of PR primary L90M, D30N,
      M46I, and V82A mutations in 7.9% of the post-HAART group, and a high frequency of
      secondary mutations (84.2%). Nucleoside RT-associated mutations were observed in
      13.2%. In the pre-HAART group, a higher frequency of RT mutations was observed
      (22.2%) and no PR primary mutations were found, in agreement with the
      introduction of protease inhibitors (PIs) in therapy during the same period. The
      identification of 7.9% of drug-naive injecting drug users already bearing RT/PR
      primary resistance mutations in the post-HAART era group constitutes a major
      concern in terms of dissemination of drug resistant viruses. The resistance
      mutations profile of the individuals may reflect the context of antiretroviral
      treatment in Brazil at the sample collection periods (1994-1997 and 1999-2001).
      In spite of the differences observed in the drug resistance profiles, similar
      frequencies of subtype B (63.0 vs. 73.7%), F (22.2 vs. 10.5%), and recombinant
      B/F (14.8 vs. 15.8%) viruses were found, respectively, in the pre- and post-HAART
      groups.

PMID- 16628576
TI  - Time course characteristics of human herpesvirus 6 specific cellular immune
      response and natural killer cell activity in patients with exanthema subitum.
AB  - The time-course of cell-mediated immunity in exanthema subitum is not well
      documented. The lymphoproliferative response to purified human herpesvirus 6 (HHV
      6) antigen and to phytohemagglutinin was measured and natural killer (NK) cell
      activities determined in three consecutive specimens obtained biweekly from 18
      young children and infants with exanthema subitum. Virus isolation and PCR
      detection of virus DNA and determination of neutralization antibody to HHV-6 and 
      7 were also carried out. The magnitude of the HHV-6 specific lymphoproliferative
      response varied; however, in most cases the time course kinetics revealed a low
      response in the acute phase with a subsequent gradual increase. In contrast, NK
      cell activities were high in the acute phase and declined gradually during
      convalescence. The lymphoproliferative response to phytohemagglutinin did not
      show a consistent trend in kinetics of time; however, dynamic changes in activity
      were observed in patients during the acute and convalescent periods. The results
      suggest that NK cells play a major role in resolving acute phase infection while
      specific lymphocyte activity develops later. The cause of the delayed development
      of HHV-6 specific lymphoproliferative response is unknown. The
      lymphoproliferative response to phytohemagglutinin ratios implied that HHV-6
      infection has some impact on host T-cell immunity during the course of exanthema
      subitum.

PMID- 16628577
TI  - Prevalence of antibodies against A and B influenza viruses in South-Western Papua
      New Guinea.
AB  - Influenza viruses remain a major cause of respiratory disease in both developed
      and developing countries. Nevertheless, there is little information on the
      prevalence of this respiratory infection in many developing countries, such as
      Papua New Guinea, since most of the available data originate from studies carried
      out in industrialized countries. In the present study, a serosurvey among
      residents of 47 remote villages of Papua New Guinea was conducted to evaluate the
      intensity of exposure to human influenza A and B viruses. The data obtained
      confirm the co-circulation of these antigenic variants, reported having
      circulated in the Southern Hemisphere. Variations in seroprevalence of influenza
      A and B virus infection were found within the study area.

PMID- 16628578
TI  - Outbreak of sapovirus infection among infants and children with acute
      gastroenteritis in Osaka City, Japan during 2004-2005.
AB  - One hundred and twenty five fecal specimens were collected from sporadic cases of
      acute gastroenteritis in a pediatric clinic in Osaka City, Japan from July 2004
      to June 2005 and tested for the presence of rotavirus, norovirus, sapovirus,
      astrovirus, and adenovirus by RT-multiplex PCR. Among diarrheal viruses detected,
      norovirus was the most prevalent (19.2%, 24 of 125), followed by group A
      rotavirus (18.4%, 23 of 125), astrovirus (1.6%, 2 of 125), and adenovirus (0.8%,
      1 of 125), respectively. Interestingly, sapovirus infection was identified with
      high incidence of 17.6% (22 of 125). Sapovirus was subjected to molecular genetic
      analysis by sequencing. It was found that sapovirus detected in this study was
      classified into four genotypes (GI/1, GI/4, GI/6, and GI/8), and sapovirus GI/6
      was predominant, followed by GI/8 and accounted for 81.8% (18 of 22) and 9.1% (2
      of 22), respectively. It was noteworthy that sapovirus GI/6 infection was
      apparently confined within the period of 5 months (August 2004 through December
      2004). This pattern of infection implied the outbreak of sapovirus GI/6 in these
      patients, which was the first outbreak of acute gastroenteritis attributed to
      sapovirus in Osaka City. Another interesting feature of the study was the
      appearance of two novel, naturally occurring recombinant sapoviruses circulating
      in the Japanese population studied. This report confirmed the presence as well as
      the importance of sapovirus causing acute gastroenteritis among Japanese infants
      and children.

PMID- 16628579
TI  - Locally acquired hepatitis E virus infection, El Paso, Texas.
AB  - Hepatitis E virus (HEV) is an enterically transmitted RNA virus that causes both
      epidemic and sporadic cases of acute hepatitis. Despite sero-surveys showing
      antibody to HEV in up to 36% of the US population, acute hepatitis E has been
      reported among individuals with no history of international travel only three
      times in the United States. We report a case of apparently locally-acquired
      hepatitis E that occurred in El Paso, Texas that was 98% similar to a previously
      isolated HEV found in swine in the United States. Like the three previous cases,
      a thorough investigation found no conclusive sources of infection. Active case
      surveillance found no additional cases.

PMID- 16628580
TI  - Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using
      real-time PCR: correlation of CMV in the vagina and adverse outcome of pregnancy.
AB  - The impact of cytomegalovirus (CMV) infection of the genital tract during
      pregnancy on adverse pregnancy outcomes is not understood fully. A real-time PCR
      assay was used to determine vaginal shedding of CMV in 993 healthy pregnant
      Japanese women and the results were compared with the outcome of pregnancy. CMV
      DNA was detected in 76 (7.7%) of the women. The outcome of pregnancy could be
      determined finally in 848 women, of whom 60 (7.1%) were CMV positive. The
      carriers of CMV had an increased miscarriage rate (RR 6.96, 95% CI 2.04-23.84, P
      < 0.01). These findings suggest that latent genital tract CMV infection
      predisposes to adverse pregnancy outcomes.

PMID- 16628581
TI  - Clonality analysis by sequence variation of the latent membrane protein 1 gene in
      patients with chronic active Epstein-Barr virus infection.
AB  - Chronic active Epstein-Barr virus (EBV) infection is a severe systemic disease
      associated with high rates of mortality and morbidity. Recent studies suggest
      that the clonal expansion of EBV-infected T or natural killer cells plays a
      crucial role in the pathogenesis of chronic active EBV infection. However, it is
      not clear whether chronic active EBV infection is truly a monoclonal disorder
      that originates from one cell. The clonality of EBV was investigated by sequence
      variation of the latent membrane protein 1 (LMP1) gene, which has a high degree
      of sequence heterogeneity. Peripheral blood mononuclear cells were obtained from
      nine Japanese patients with chronic active EBV infection and four with infectious
      mononucleosis. A carboxyl-terminal region of the LMP1 gene was analyzed by
      polymerase chain reaction (PCR). The amplified PCR products were subcloned, and
      18 clones from each sample were sequenced. Patients with chronic active EBV
      infection each had two to five different LMP1 nucleotide sequences, whereas
      patients with infectious mononucleosis each had one to seven different sequences.
      Patients with chronic active EBV infection and infectious mononucleosis both had
      one dominant sequence. Longitudinal analysis was performed in four patients with
      chronic active EBV infection, in whom the dominant strains were found to have
      remained unchanged for several years. The results suggest that EBV in patients
      with chronic active EBV infection was polyclonal, although clonal expansion may
      occur. Collectively, these findings are critical to clarify further the
      pathogenesis of chronic active EBV infection and aid in the development of
      effective treatment strategies.

PMID- 16628582
TI  - Adverse response of non-indigenous cattle of European breeds to live attenuated
      Smithburn Rift Valley fever vaccine.
AB  - Three hundred eighteen European cows and 115 buffaloes were vaccinated with
      locally prepared Smithburn vaccine, of which, 100 cows and 20 buffaloes were
      pregnant. Twenty-eight cows aborted within 72 days post-vaccination, buffaloes
      did not abort. Blood samples collected 77 days post-vaccination from aborted
      cows, 17 pregnant cows, 5 pregnant buffaloes, and 32 non-pregnant cows. Sera were
      tested by ELISA for anti-RVF IgM and IgG. All aborted cows were strongly positive
      for IgG. Five of 17 cows and two of five buffaloes that did not abort were IgG
      positive. The percentage of IgM positives in aborted cows was 25% and 0% in non
      aborted cows. The percentage of IgG positives in pregnant non-aborted cows was
      lower than in non-pregnant cows. The percentage of IgG positives of non-pregnant
      cows was lower than pregnant aborted cows. Virus was isolated from one aborted
      fetus. The nucleotide sequence of fetus virus was compared to Smithburn of
      Onderstepoort, local Smithburn and virus isolates from 1993 to 1994 and 1977 RVF
      outbreaks. The nucleotide sequences of Onderstepoort and Egyptian Smithburn
      vaccines were almost identical. The sequences of 1993-1994 isolates were
      identical to 1977 outbreak virus. Virus from the fetus had two mutations; it is
      apparently a variant that is genetically distant from local Smithburn and
      Onderstepoort vaccines. Fetus virus was genetically distant from virus of
      1993/1994 and 1977 outbreaks. In conclusion, antibody response to vaccination
      with local Smithburn had occurred in some, but not all the cows and buffaloes.
      Virus isolation from the fetus suggests in utero transmission of used vaccine
      virus, which resulted in high abortions in European cows.

PMID- 16628583
TI  - HHV-6 and HHV-7 antigenemia related to CMV infection after liver transplantation.
AB  - BACKGROUND: Betaherpesviruses human herpesvirus-6 and -7 (HHV-6, HHV-7), which
      are closely related to cytomegalovirus (CMV), have been reported in transplant
      patients. In this retrospective study, we investigated the occurrence of HHV-6
      and HHV-7 antigenemia in relation to symptomatic CMV infection after liver
      transplantation. METHODS: Sample material from 64 adult liver transplant
      recipients was included in the study. The patients were monitored weekly for CMV,
      HHV-6, and HHV-7. CMV infections were diagnosed by pp65-antigenemia and viral
      cultures. Concomitantly HHV-6 and HHV-7 antigens were demonstrated in peripheral
      blood mononuclear cells by monoclonal antibodies against both variants A and B
      and immunoperoxidase staining. Altogether 540 post-transplant blood specimens
      were analyzed. RESULTS: Nineteen patients (30%) developed symptomatic CMV pp65
      antigenemia during the first 3 months (mean 33 days, range 5-62 days) post
      transplantation and were treated with intravenous ganciclovir. Concurrent HHV-6
      antigenemia was detected in 16/19 (median 9 days, range 6-24 days) and HHV-7
      antigenemia 15/19 patients (median 17 days, range 5-58 days) after
      transplantation. HHV-6 appeared before CMV in most cases (12/16), HHV-7 usually
      together with CMV. In those cases that HHV-6 preceded CMV antigenemia, it also
      was a possible cause of graft dysfunction. HHV-7 and CMV were so closely
      overlapping, that no symptoms could solely be linked with HHV-7. CONCLUSION: HHV
      6 and HHV-7 antigenemia usually occurred together with symptomatic CMV infection
      after liver transplantation. HHV-6 preceded CMV, but HHV-7 appeared together with
      CMV. Further investigation of the clinical significance of HHV-6 and HHV-7
      antigenemia in organ transplant patients is necessary.

PMID- 16628584
TI  - High-risk human papillomavirus infection of the genital tract of women with a
      previous history or current high-grade vulvar intraepithelial neoplasia.
AB  - Human papillomavirus (HPV) infection is associated with high-grade vulvar
      intraepithelial neoplasia (VIN-3). The prevalence of anogenital HPV infection in
      women with previously treated VIN-3 has not been documented yet. This cross
      sectional study compared high-risk HPV DNA detection rates in women with past (n
      = 30) and current (n = 22) VIN-3 to those without current or past VIN (n = 86).
      HPV DNA was detected in vulvar and cervical samples with Hybrid Capture 2 (HC-2).
      Smoking was associated in multivariate analysis with current VIN-3 (odds ratio
      (OR) 8.3, 95% confidence interval (CI) 2.0-8.2) and any VIN-3 history (OR 6.5,
      95% CI 2.5-16.5). High-risk HPV DNA was found on the vulva of 64%, 33%, and 20%
      of women with current VIN-3, past VIN-3, and without previous or current VIN,
      respectively. After controlling for age and smoking, high-risk HPV vulvar
      infection was associated with cervical high-risk HPV infection (OR 8.6, 95% CI
      2.8-26.5; P = 0.001). After controlling for age, HPV infection was more often
      multifocal in women with current VIN-3 compared to women with previous but no
      current VIN-3 lesion (OR 17.6, 95% CI 1.4-227.2). Multifocal vulvar HPV infection
      was detected in women with previous or active VIN-3. Longitudinal studies are
      required to determine if the multifocality of HPV infection on the vulva could
      explain the high recurrence rate of VIN-3.

PMID- 16628585
TI  - Decreased bacterial clearance from the lungs of mice following primary
      respiratory syncytial virus infection.
AB  - Virus respiratory infections often precede bacterial pneumonia in healthy
      individuals. In order to determine the potential role of respiratory syncytial
      virus (RSV) in bacterial secondary infections, a mouse sequential pulmonary
      infection model was developed. Mice were exposed to RSV then challenged with
      Streptococcus pneumoniae (StPn). Exposure of BALB/c mice to 10(6)-10(7) plaque
      forming units (pfu) of virus of RSV significantly decreased StPn clearance 1-7
      days following RSV exposure. This finding was not restricted to StPn alone:
      exposure to RSV followed by Staphylococcus aureus (SA) or Pseudomonas
      aeruginosa(PA) resulted in similar decreases in bacterial clearance. Both
      bronchoalveolar lavage (BAL) cell counts and pulmonary histopathology
      demonstrated that RSV-StPn exposed mice had increased lung cellular inflammation
      compared to mice receiving StPn or RSV alone. The effect of RSV infection on
      bacterial clearance was dependent on the mouse genetic background: C57BL/6J mice
      (relatively resistant to RSV infection) demonstrated a modest change in StPn
      clearance following RSV exposure, whereas FVBN/J mice (similar to the BALB/cJ
      mice in RSV susceptibility) demonstrated a similar degree of RSV-associated
      decrease in StPn clearance 7 days following RSV exposure. Neutrophils from the
      RSV-StPn sequentially exposed BALB/cJ mice were functionally altered-produced
      greater levels of peroxide production but less myeloperoxidase (MPO) compared to
      mice receiving StPn alone. These data demonstrate that RSV infection decreases
      bacterial clearance, potentially predisposing to secondary bacterial pneumonia
      despite increased lung cellular inflammation, and suggest that functional changes
      occur in the recruited neutrophils that may contribute to the decreased bacterial
      clearance.

PMID- 16628586
TI  - Human immunodeficiency virus type 1 and hepatitis C virus co-infection and viral
      subtypes at an HIV testing center in Brazil.
AB  - Human immunodeficiency virus (HIV) testing sites have been recognized recently as
      potential settings for hepatitis C virus (HCV) screening since both viruses share
      common routes of transmission. HIV and HCV prevalence, predictors, co-infection
      rates, and viral subtypes were studied in 592 attendants at an anonymous HIV
      Counseling and Testing Center in central Brazil. Anti-HIV-1 and -HCV antibodies
      were screened by ELISA, and Western blots were used to confirm HIV infection.
      Among HIV-seropositive samples, reverse transcriptase-polymerase chain reaction
      (RT-PCR) and nested-PCR were used to subtype HIV-1 by the Heteroduplex Mobility
      Analysis (HMA) and HCV by the line probe assay (INNO-LiPA). HIV and HCV
      seroprevalence was 3.2% (95% CI 2.0-4.9) and 2.5% (95% CI 1.5-4.0), respectively.
      Intravenous drug use was the risk factor most strongly associated with both HIV
      and HCV infections, even in a population with few intravenous drug users (n = 6);
      incarceration was also associated with HCV. HIV/AIDS-positive sexual partner and
      homosexual/bisexual behaviors were associated independently with HIV-1. The
      prevalence of HCV infection among HIV-positive persons was 42% (95% CI 20-66),
      higher than in HIV-negative persons (1.2%; 95% CI 0.5-2.5). HIV-1 subtype B was
      identified in the env and gag regions of the genome. HCV subtype 3a predominated
      among co-infected persons and one HCV subtype 1a was detected. Overall, a similar
      prevalence of HIV and HCV infections and a higher prevalence of HCV among HIV
      positive persons were observed. Integrated HIV and HCV screening at HIV testing
      sites may represent a unique opportunity to provide diagnosis and prevention
      strategies at a single visit.

PMID- 16628587
TI  - Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV
      positive and -negative pregnant women in Burkina Faso.
AB  - Toxoplasma gondii (T. gondii) infections can cause serious complications in HIV
      infected pregnant women, leading to miscarriage, stillbirth, birth defects (e.g.,
      mental retardation, blindness, epilepsy etc.) and could favor or enhance the
      mother-to-child transmission of HCV, HBV, and HIV vertical transmission. From May
      20, 2004 to August 3, 2005, 336 18-45 years aged pregnant women, were enrolled
      for an investigation of the prevalence of serum antibodies against T. gondii,
      HCV, HBV, and HIV using ELISA. The prevalence of T. gondii, HCV, and HBV in
      pregnant women was 25.3%, 5.4%, and 9.8%, respectively and the HIV serostatus
      (61.6%) seems to be associated with greater prevalence rates of both T. gondii
      (28.5% vs. 20.2%) and HBV (11.6% vs. 7.0%). Without taking into account HIV, only
      65.5% (220 of 336) of the women were not infected with these agents. The co
      infection rate between HIV-infected and -negative women was different
      statistically: T. gondii/HBV 0.048 versus 0.015, T. gondii/HCV 0.014 versus
      0.008, and HCV/HBV 0.005 versus 0.008, respectively. The elevated co-infection
      rate in HIV-positive women demonstrated that they are exposed to T. gondii, HCV,
      and HBV infections prevalently by sexual contact.

PMID- 16628588
TI  - Peptide-loaded dendritic-cell vaccination followed by treatment interruption for
      chronic HIV-1 infection: a phase 1 trial.
AB  - Immune response enhanced by therapeutic HIV-1 vaccine may control viral
      proliferation after discontinuation of highly active antiretroviral therapy
      (HAART). Although which strategies for therapeutic vaccination are feasible
      remains controversial, application of dendritic cells (DCs) as a vaccine adjuvant
      represents a promising approach to improving deteriorated immune function in HIV
      1-infected individuals. The safety and efficacy of DC-based vaccine loaded with
      HIV-1-derived cytotoxic T lymphocytes (CTL) peptides were thus investigated in
      this study. Autologous DCs loaded with seven CTL peptides with HLA-A*2402
      restriction were immunized to four HIV-1-infected individuals under HAART. In
      terms of safety, peptide-loaded DCs were well tolerated, and only mild local and
      general symptoms were observed during vaccine administration. ELISPOT assays to
      detect IFN-gamma production in CD8(+) lymphocytes revealed a limited breadth of
      responses to immunized peptides in two of four participants, but no response in
      the remaining two participants. Differences in immunological response might be
      attributable to the fact that responders displayed higher nadir CD4 counts before
      starting HAART and were immunized with a larger number of DCs per reactive
      peptide than non-responders. Discontinuation of HAART after vaccination failed to
      lower viral set points compared to those before starting HAART. This early
      outcome warrants further exploration to elucidate the therapeutic value of
      vaccination with DCs in HIV-1 infection.

PMID- 16628589
TI  - Hepatitis B virus genotypes, core promoter variants, and precore stop codon
      variants in patients infected chronically in North-Eastern Italy.
AB  - The hepatitis B virus (HBV) genotypes distribution and the core promoter
      (CP)/precore (PC) variability were evaluated by a line probe assay in 272
      patients infected chronically enrolled consecutively in an area of the North
      Eastern Italy. Seven out of the eight genotypes were detected. Italian subjects
      (83% of the sample) were infected mainly by genotype D (73%) and A (26%);
      genotype F, and genotype H, were detected only in one subject. In foreigners, the
      genotype distribution reflected the distribution described for the areas of
      origin, that is, in Asia genotypes B, C, and D; in Africa genotypes A and E. CP
      and PC variants prevalence rates were 51% and 60%, respectively, and were
      significantly higher in Italian patients, probably in relation to their older
      age. In the analysis restricted to genotypes A and D, PC wild type was linked
      strongly to genotype A (OR = 4.08, 95% CI = 3.07-5.43, P < 0.0001). In genotype A
      infected patients, only e seroconversion was associated significantly with CP
      variants. In genotype D-infected subjects, CP variants were linked significantly
      to older age and to a higher e seroconversion rate, while PC variants also showed
      a strong relationship with an ALT lower activity and a lower viral load. In
      multivariate analysis, HBeAg positivity was associated strongly and independently
      with younger age, genotype A and CP wild type. Independent determinants of higher
      viral loads were recognized by increasing age, in male gender and concomitant
      presence of HBeAg and the CP wild type virus.

PMID- 16628590
TI  - Patterns of serum type 1 and type 2 immune markers in healthy carriers of HTLV-I.
AB  - Type 1 immunity appears to be diminished in healthy Japanese carriers of human T
      lymphotropic virus type I (HTLV-I), but type 2 status remains undetermined. To
      further examine the subclinical effect of HTLV-I on host immunity, we measured
      serum antibodies to the Epstein-Barr virus (EBV) in 415 healthy Japanese adults
      to broadly characterize type 1 status. Levels of the type 2 biomarkers total
      immunoglobulin E (IgE), soluble CD23 (sCD23), and soluble CD30 (sCD30) were
      assessed in 167, 142, and 135 of these subjects, respectively. We analyzed the
      association of HTLV-I with levels of each serum marker using linear and logistic
      regression. Altered EBV antibody profiles that are consistent with deficient type
      1 immunity were more prevalent in HTLV-I carriers than non-carriers (odds ratio
      (OR) = 2.8, 95% confidence interval (CI) = 1.5-5.3). Carriers also had 45% lower
      total IgE levels (P = 0.04) than non-carriers. In contrast, HTLV-I infection was
      not significantly associated with elevated levels of sCD23 or sCD30. These
      observations are contrary to our expectation of elevated type 2 biomarkers among
      carriers. We conclude that in this population, healthy carriers of HTLV-I may
      have subclinical deficiencies in both type 1 and type 2 immunity, and that type 1
      and type 2 immunity are not necessarily reciprocal in persons with subclinical
      immune dysregulation.

PMID- 16628591
TI  - SYBR green and TaqMan real-time PCR assays are equivalent for the diagnosis of
      dengue virus type 3 infections.
AB  - Dengue is the most important arthropod-borne viral disease in the world. A rapid
      diagnostic test for dengue is warranted, and real-time polymerase chain reaction
      may improve diagnosis. TaqMan and Sybr Green systems were evaluated for the
      diagnosis of dengue virus type 3 (DENV-3) infections. Out of 77 patients with
      clinical suspicion of dengue infection, specific IgM antibodies were detected in
      40 patients. DENV-3 was detected and quantitated in 17 IgM-positive samples by
      both systems. These assays were shown to be rapid, and specific for detection of
      DENV-3, and that for diagnostic purposes, there is no difference between these
      two assays.

PMID- 16628592
TI  - Dedication to Dr. Robert Boyd.

PMID- 16628593
TI  - Combining desorption electrospray ionization mass spectrometry and nuclear
      magnetic resonance for differential metabolomics without sample preparation.
AB  - Desorption electrospray ionization mass spectrometry (DESI-MS) and nuclear
      magnetic resonance (NMR) spectroscopy are used to provide data on urine examined
      without sample preparation to allow differentiation between diseased (lung
      cancer) and healthy mice. Principal component analysis (PCA) is used to shortlist
      compounds with potential for biomarker screening which are responsible for
      significant differences between control urine samples and samples from diseased
      animals. Similar PCA score plots have been achieved by DESI-MS and NMR, using a
      subset of common detected metabolites. The common compounds detected by DESI and
      NMR have the same changes in sign of their concentrations thereby indicating the
      usefulness of corroborative analytical methods. The effects of different solvents
      and surfaces on the DESI mass spectra are also evaluated and optimized. Over 80
      different metabolites were successfully identified by DESI-MS and tandem mass
      spectrometry experiments, with no prior sample preparation.

PMID- 16628594
TI  - Atypical ductus venosus blood flow pattern during a prolonged fetal heart rate
      deceleration in labor.

PMID- 16628595
TI  - Discovery of fatty acid ester metabolites of spirolide toxins in mussels from
      Norway using liquid chromatography/tandem mass spectrometry.
AB  - Cultured mussels sampled in the spring of 2002 and 2003 from Skjer, a location in
      the Sognefjord, Norway, tested positive in the mouse bioassay for lipophilic
      toxins. In a previous report, it was established that a number of spirolides,
      cyclic imine toxins produced by the phytoplankton Alexandrium ostenfeldii, were
      present in the mussels and were responsible for the observed toxicity. The main
      toxin proved to be a new compound named 20-methyl spirolide G. In subsequent
      studies, a delayed onset of spirolide-like symptoms in the mouse bioassay
      exceeding the usual time limit of 20 min was observed in some samples, with
      symptoms and death appearing as long as 45-50 min after injection. It is well
      known that shellfish can extensively metabolize other toxins, such as okadaic
      acid and the dinophysistoxins, to fatty acid acyl esters and it is also known
      that a delayed onset of toxic symptoms with such metabolites can occur. Analyses
      performed with liquid chromatography/tandem mass spectrometry (LC/MS/MS) have
      revealed a complex mixture of esters of 20-methyl spirolide G in the contaminated
      mussels. Precursor ion scanning has delineated the range of fatty acid esters
      involved, while product ion scanning has provided information on structure.
      Identity was also supported through reaction of 20-methyl spirolide G with
      palmitic anhydride, which produced a derivative with a retention time and
      spectrum identical with one putative metabolite, 17-O-palmitoyl-20-methyl
      spirolide G.

PMID- 16628596
TI  - Analytical application of acetate anion in negative electrospray ionization mass
      spectrometry for the analysis of triterpenoid saponins--ginsenosides.
AB  - Ginsenosides containing different numbers of glycosyl groups can be easily
      differentiated based on the formation of characteristic ginsenoside-acetate
      adduct anions and deprotonated ginsenosides generated by electrospray ionization
      (ESI) of methanolic solutions of ginsenosides (M) and ammonium acetate (NH4OAc).
      Ginsenosides containing two glycosyl groups gave a characteristic mass spectral
      pattern consisting of [M+2OAc]2-, [M-H+OAc]2- and [M-2H]2- ions with m/z values
      differing by 30 Th, while this mass spectral pattern was not observed for
      ginsenosides containing one glycosyl group. Formation of [M+2OAc]2- was
      influenced by the chain length of glycosyl groups and was used to differentiate
      the ginsenosides containing different combinations of monosaccharide and
      disaccharide units in the glycosyl groups. Under identical collisional activation
      conditions, [M+OAc]-, [M-H+OAc]2- and [M+2OAc]2- underwent proton abstractions
      predominantly to generate [M-H]-, [M-2H]2- and [M-H+OAc]2- ions, respectively.
      The ion intensity ratios, I[M-H](-/I) [M+OAc]-, I[M-2H](2-/I) [M-H+2OAc]2- and
      I[M-H+OAc](2-/I) [M+OAc]2-, being sensitive to the structural differences of
      ginsenosides, could differentiate the isomeric ginsenosides, including (i) Rf,
      F11 and Rg1, (ii) Rd and Re, and (iii) Rb2 and Rc. Additionally, NH4OAc was found
      to enhance the sensitivity of detection of ginsenosides in the form of [M-H]-
      down to the femtomole level.

PMID- 16628597
TI  - Three-dimensional ultrasonographic demonstration of agenesis of the 12th rib in a
      fetus with trisomy 21.

PMID- 16628598
TI  - Dedication to Dr. Robert Kinnear Boyd.

PMID- 16628599
TI  - Dedication to Robert Kinnear Boyd.

PMID- 16628600
TI  - Liquid chromatographic tandem mass spectrometric assay for the uremic toxin 3
      carboxy-4-methyl-5-propyl-2-furanpropionic acid in human plasma.

PMID- 16628601
TI  - Detection of artifacts and peptide modifications in liquid chromatography/mass
      spectrometry data using two-dimensional signal intensity map data visualization.
AB  - We demonstrate how visualization of liquid chromatography/mass spectrometry data
      as a two-dimensional signal intensity map can be used to assess the overall
      quality of the data, for the identification of polymer contaminants and
      artifacts, as well as for the confirmation of post-translational modifications.

PMID- 16628602
TI  - Depression and self-reported depressive symptoms in multiple system atrophy
      compared to Parkinson's disease.

PMID- 16628603
TI  - Temporal discrimination of two passive movements in writer's cramp.
AB  - Although movement abnormalities are predominant symptoms of dystonia, patients
      also have alterations in temporal as well as spatial discrimination of cutaneous
      inputs. Here, we use a recently described method to test whether deficits also
      exist in temporal discrimination of proprioceptive inputs. Percutaneous
      electrical stimulation of the motor point of the first dorsal interosseous (FDI)
      muscle, and of the flexor carpii radialis (FCR) muscle separately, was used to
      produce a nonpainful contraction of the muscles that caused index finger
      abduction and wrist flexion, respectively. In 10 patients with writer's cramp and
      in 10 healthy subjects, pairs of stimuli separated by different time intervals
      were given and subjects were asked to report whether they perceived a single or a
      double index finger abduction movement or wrist flexion. The threshold value was
      the shortest interval at which the subjects reported two separated movements
      (temporal discrimination motor threshold [TDMT]). In both writer's cramp patients
      and controls, TDMTs were higher for FCR than for FDI. But in contrast to the
      reduced temporal discrimination reported for cutaneous sensation, there was no
      significant difference in either muscle between TDMT in patients and normal
      subjects. We conclude that temporal processing of muscle and cutaneous afferents
      is differentially affected in focal hand dystonia.

PMID- 16628604
TI  - Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single
      family.
AB  - Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant
      neurodegenerative disorders caused by mutations in two different genes. We
      identified mutations for SCA2 and SCA3 segregating simultaneously in a single
      Brazilian family. The index patient had SCA2, whereas her two second-degree
      cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who
      presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3
      patients, who had only mild cerebellar vermian atrophy. In such situations,
      molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and
      eventual errors in predictive testing of unaffected family members.

PMID- 16628605
TI  - Overexpression of pituitary tumor transforming gene 1 in HCC is associated with
      angiogenesis and poor prognosis.
AB  - The pituitary tumor transforming gene 1 (PTTG1) protein is cell-cycle regulated
      and is identified as a human securin that inhibits sister chromatid separation
      and is involved in transformation and tumorigenesis. PTTG1 has very low or
      undetectable expression in most normal human tissues, but it is abundantly
      expressed in malignant cell lines and pituitary tumors. In this study, we
      investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC)
      specimens using quantitative real-time reverse transcription polymerase chain
      reaction analysis. We found that, compared with corresponding noncancerous liver
      tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/beta-actin; 0.443 +/-
      0.073 vs. 0.068 +/- 0.007; P < .0001). Furthermore, we found a significant
      correlation between PTTG1 expression and serum alpha-fetoprotein level (P <
      .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA
      (mRNA) expression was an independent prognostic factor for disease-free (odds
      ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover,
      we discovered a significant relationship between PTTG1 expression and
      intratumoral microvessel density. Our data supported an important role for PTTG1
      mediated upregulation of fibroblast growth factor (FGF)-2, one of angiogenesis
      and modulation of tumor progression, in hepatocarcinogenesis. In conclusion,
      PTTG1 might be critically involved in the development of HCCs through the
      promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest
      that PTTG1 mRNA expression has prognostic significance for the survival of
      postoperative patients with HCC.

PMID- 16628606
TI  - Toward brain correlates of natural behavior: fMRI during violent video games.
AB  - Modern video games represent highly advanced virtual reality simulations and
      often contain virtual violence. In a significant amount of young males, playing
      video games is a quotidian activity, making it an almost natural behavior.
      Recordings of brain activation with functional magnetic resonance imaging (fMRI)
      during gameplay may reflect neuronal correlates of real-life behavior. We
      recorded 13 experienced gamers (18-26 years; average 14 hrs/week playing) while
      playing a violent first-person shooter game (a violent computer game played in
      self-perspective) by means of distortion and dephasing reduced fMRI (3 T; single
      shot triple-echo echo-planar imaging [EPI]). Content analysis of the video and
      sound with 100 ms time resolution achieved relevant behavioral variables. These
      variables explained significant signal variance across large distributed
      networks. Occurrence of violent scenes revealed significant neuronal correlates
      in an event-related design. Activation of dorsal and deactivation of rostral
      anterior cingulate and amygdala characterized the mid-frontal pattern related to
      virtual violence. Statistics and effect sizes can be considered large at these
      areas. Optimized imaging strategies allowed for single-subject and for single
      trial analysis with good image quality at basal brain structures. We propose that
      virtual environments can be used to study neuronal processes involved in semi
      naturalistic behavior as determined by content analysis. Importantly, the
      activation pattern reflects brain-environment interactions rather than stimulus
      responses as observed in classical experimental designs. We relate our findings
      to the general discussion on social effects of playing first-person shooter
      games.

PMID- 16628607
TI  - Retrospective motion correction protocol for high-resolution anatomical MRI.
AB  - Modern computational brain morphology methods require that anatomical images be
      acquired at high resolution and with a high signal-to-noise ratio. This often
      translates into long acquisition times (>20 minutes) and images susceptible to
      head motion. In this study we tested retrospective motion correction (RMC),
      common for functional MRI (fMRI) and PET image motion correction, as a means to
      improve the quality of high-resolution 3-D anatomical MR images. RMC methods are
      known to be effective for correcting interscan motion; therefore, a single high
      resolution 3-D MRI brain study was divided into six shorter acquisition segments
      to help shift intrascan motion into interscan motion. To help reduce intrascan
      head motion, each segment image was reviewed for motion artifacts and repeated if
      necessary. Interscan motion correction was done by spatially registering images
      to the third image and forming a single average motion-corrected image. RMC was
      tested on 35 subjects who were considered at high risk for head motion. Our
      results show that RMC provided better contrast-to-noise ratio and boundary detail
      when compared to nonmotion-corrected averaged images.

PMID- 16628608
TI  - Effect of word and syllable frequency on activation during lexical decision and
      reading aloud.
AB  - This functional MRI (fMRI) study investigated the effect of lexical and syllable
      frequency on visual word processing during lexical decision and reading aloud.
      Previous research has shown a dissociation of syllable and word frequency effects
      in Spanish using behavioral and electrophysiological measures, suggesting that
      sublexical (syllabic) representations are computed and mediate the firing of
      lexical candidates. Here, we characterize the neuroanatomical basis of these
      lexical and sublexical manipulations and their dependence on task. During lexical
      decision, words with low vs. high lexical frequency increased activation in left
      frontal, anterior cingulate, supplemental motor area (SMA), and pre-SMA regions;
      while words with high vs. low syllable frequency increased activation in a left
      anterior inferior temporal region. In contrast, when the words were read aloud
      those with low vs. high syllable frequency increased activation in the left
      anterior insula, with no other significant effects. On the basis of the
      neuroanatomy, we propose that the contrasting effects of syllable frequency
      during lexical decision and reading aloud reflect two different cognitive
      processes in visual word processing. Specifically, words with high-frequency
      syllables may increase lexical competition in the inferior temporal lobe while
      facilitating articulatory planning in the left anterior insula.

PMID- 16628609
TI  - A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic
      evidence that the sodium potassium pump contributes to left-right asymmetry
      downstream or in parallel to nodal flow.
AB  - While there is a good conceptual framework of dorsoventral and anterioposterior
      axes formation in most vertebrate groups, understanding of left-right axis
      initiation is fragmentary. Diverse mechanisms have been implied to contribute to
      the earliest steps of left-right asymmetry, including small molecule signals, gap
      junctional communication, membrane potential, and directional flow of
      extracellular liquid generated by monocilia in the node region. Here we
      demonstrate that a mutation in the zebrafish Na,K-ATPase subunit atp1a1a causes
      left-right defects including isomerism of internal organs at the anatomical
      level. The normally left-sided Nodal signal spaw as well as its inhibitor lefty
      are expressed bilaterally, while pitx2 may appear random or bilateral. Monocilia
      movement and fluid circulation in Kupffer's vesicle are normal in atp1a1a(m883)
      mutant embryos. Therefore, the Na,K-ATPase is required downstream or in parallel
      to monocilia function during initiation of left-right asymmetry in zebrafish.

PMID- 16628610
TI  - Ultrasound-guided radiofrequency-driven umbilical cord occlusion: an in-vitro
      study.
AB  - OBJECTIVES: To assess the ability and safety of radiofrequency (RF) to induce
      cord thermal lesions using in-vitro perfused umbilical cords. METHODS: Nineteen
      human term umbilical cords were cannulated at both ends and perfused continuously
      with saline serum in a saline serum bath (37 degrees C). The RF electrode was
      then inserted into the cord close to the umbilical vein. Different RF power and
      temperature controls were applied to determine the optimal RF procedure in terms
      of cord tissue injury and safety in nine experiments. The safety of RF procedures
      was investigated in ten cords by measuring temperature changes at different sites
      close to the RF electrode insertion and the impact of RF on cord narrowing was
      evaluated by continuous monitoring of intraluminal pressure. Subsequent
      histopathological analysis was carried out in all cases. RESULTS: The optimal RF
      procedure reached a temperature of 100 degrees C in 10 min. RF produced a
      significant increase in intraluminal pressure (from 54.2 +/- 16.4 mmHg at
      baseline to 118.3 +/- 42.7 mmHg after 10 min, P < 0.05). There was no significant
      increase in temperature next to the site of insertion during the RF procedure.
      Histopathological analysis confirmed a > 30% decrease in cord and vein diameter.
      Cord tissue lesions were characterized by damage in the vessel walls and in the
      surrounding Wharton's jelly. CONCLUSION: Our results suggest that RF might be a
      feasible and safe technique to induce occlusion of umbilical vessels. Further in
      vivo experiments are needed to assess its ability to induce a complete occlusion
      of the umbilical cord.

PMID- 16628611
TI  - Enterovirus 71 infection induces Fas ligand expression and apoptosis of Jurkat
      cells.
AB  - T-cell depletion is found in enterovirus 71 (EV71)-infected patients with
      pulmonary edema. However, the mechanism that causes T-cell depletion is unclear.
      To address this question, the effects of EV71 infection on the cell viability of
      human Jurkat T cells were studied. Viable viruses were recovered from both the
      culture supernatant and the cell lysate of Jurkat cells after EV71 infection.
      Results from reverse-transcription polymerase chain reaction (RT-PCR) and
      immunofluorescence assay confirmed further the presence of EV71 negative-strand
      RNA and antigen, respectively, in EV71-infected Jurkat cells. The viability of
      the Jurkat cells decreased after 48 hr of EV71 infection. Both terminal
      transferase end labeling (TUNEL) and DNA fragmentation assays demonstrated that
      the apoptosis of EV71-infected Jurkat cells had increased. In addition, the
      expression of Fas ligand (FasL) in EV71-infected Jurkat cells increased at both
      mRNA and surface expression levels. Taken together, these results confirmed that
      EV71 infected T cells and induced FasL expression, which may contribute to T-cell
      apoptosis during EV71 infection.

PMID- 16628612
TI  - Real-time human fetal aorta velocity profile using global acquisition and signal
      processing (GASP).

PMID- 16628613
TI  - A case of hydatid cyst associated with postpartum maternal death.
AB  - A young, apparently healthy woman from a rural area in South Africa presented in
      the third trimester of pregnancy with a symptomatic abdominal mass between the
      uterine fundus and liver. The etiology was established to be an echinococcus cyst
      of the liver and medical treatment was initiated. The fetal outcome was good but
      the mother died 3 days postpartum due to an unusual but devastating complication
      of the hydatid cyst.

PMID- 16628614
TI  - Comparison of extrinsic efferent innervation of guinea pig distal colon and
      rectum.
AB  - The extrinsic efferent innervation of the distal colon and rectum of the guinea
      pig was compared, by using retrograde tracing combined with immunohistochemistry.
      Application of the carbocyanine tracer DiI to the rectum filled significantly
      greater numbers of extrinsic neurons than similar injections into the distal
      colon. Approximately three-fourths of all filled neurons from either location
      were either sympathetic or parasympathetic; the rest were spinal sensory neurons.
      Nerve cell bodies in sympathetic prevertebral ganglia labelled from the two
      regions were similar in number. Both regions were innervated by sympathetic
      neurons in paravertebral ganglia; however, the rectum received much more input
      from this source than the colon. The rectum received significantly more input
      from pelvic ganglia than the colon. The rectum also received direct innervation
      from two groups of neurons in the spinal cord. Neurons located in the spinal
      parasympathetic nucleus in segment S2 and S3 were labelled by DiI injected into
      the rectal wall. Similar numbers of neurons, located in intermediolateral cell
      column and dorsal commissural nucleus of lumbar segments, also projected directly
      to rectum, but not colon. The great majority (>80%) of retrogradely labelled
      nerve cell bodies in sympathetic ganglia were immunoreactive for tyrosine
      hydroxylase. In pelvic ganglia, retrogradely labelled neurons contained choline
      acetyltransferase and/or nitric oxide synthase or tyrosine hydroxylase. Although
      the rectum and colon in this species are continuous and macroscopically
      indistinguishable, they have significantly different patterns of extrinsic
      efferent innervation, presumably reflecting their different functions.

PMID- 16628615
TI  - Enkephalinergic afferents of the centromedial amygdala in the rat.
AB  - The connectivity of the amygdaloid complex has been extensively explored with
      both anterograde and retrograde tracers. Even though the afferents of the
      centromedial amygdala [comprising the central (CEA) and medial (MEA) amygdaloid
      nuclei] are well established, relatively little is known about the neuropeptide
      phenotype of these connections. In this study, we first examined the distribution
      of mu-opioid receptor (MOR) and delta-opioid receptor (DOR) in the amygdala via
      in situ hybridization and immunohistochemistry. We then investigated the
      distribution of Met-enkephalin (ENK) and Leu-ENK fibers with immunohistochemistry
      and examined the distribution of preproenkephalin mRNA in the amygdala by using
      in situ hybridization. Finally, we examined the ENK projections to the CEA and
      MEA by using stereotaxic injections of the retrograde tracer cholera toxin
      subunit B or fluorogold revealed by immunohistochemistry combined with in situ
      hybridization to identify ENKergic neurons. Our results indicate that the
      centromedial amygdala receives ENK afferents, as indicated by the presence of
      MOR, DOR, and ENK fibers in the CEA and MEA, originating primarily from the bed
      nucleus of the stria terminalis (BST) and from other amygdaloid nuclei. The
      posterior BST, the basomedial nucleus (BMA), and the cortical nucleus of the
      amygdala (COA) were found to be the major ENK afferents of the MEA, whereas the
      anterolateral BST, the COA, the MEA, and the BMA provided the main ENKergic
      innervation of the CEA. In addition, we found that the ventromedial nucleus of
      the hypothalamus and the pontine parabrachial nucleus provide a moderate ENK
      input to the CEA and MEA. The functional implications of these connections in
      stress, anxiety, and nociception are discussed.

PMID- 16628616
TI  - Trigeminovestibular and trigeminospinal pathways in rats: retrograde tracing
      compared with glutamic acid decarboxylase and glutamate immunohistochemistry.
AB  - This study identified neurons in the sensory trigeminal complex with connections
      to the medial (MVN), inferior (IVN), lateral (LVN), and superior (SVN) vestibular
      nuclei or the spinal cord. Trigeminovestibular and trigeminospinal neurons were
      localized by injection of retrograde tracers. Immunohistochemical processing
      revealed gamma-aminobutyric acid (GABA)- and glutamate-containing neurons in
      these two populations. Trigeminovestibular neurons projecting to the MVN and the
      IVN were in the caudal principal nucleus (5P), pars oralis (5o), interpolaris
      (5i), and caudalis (5c) and scattered throughout the rostral 5P. Projections were
      bilateral to the IVN, with an ipsilateral dominance to the MVN, except from the
      rostral 5P, which was contralateral. Neurons projecting to the LVN were numerous
      in the ventral caudal 5P and the 5o and less abundant in the rostral 5P, 5i, and
      5c. Our results suggested that only 5P and 5o project to the dorsal LVN. Neurons
      projecting to the SVN were in the dorsal 5P, 5o, and 5i but not in 5c.
      Trigeminospinal neurons were mainly in the ventral 5o and 5i and in the lateral
      5c, rarely or never in 5P. Among trigeminovestibular neurons, most of the somas
      were immunoreactive for glutamate, but some reacted for GABA. Among
      trigeminospinal neurons, the number of somas immunoreactive for each of the two
      amino acids was similar. Trigeminal terminals were observed in contact with
      vestibulospinal neurons in the IVN and LVN, giving evidence of a
      trigeminovestibulospinal pathway. Therefore, inhibitory and excitatory facial
      inputs may contribute through trigeminospinal or trigeminovestibulospinal
      pathways to the control of head/neck movements.

PMID- 16628617
TI  - Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal
      plate: Studies in chick and mouse embryos.
AB  - We investigated in the mouse and chick the neuroepithelial origin and development
      of the locus coeruleus (LoC), the most important noradrenergic neuronal
      population in the brain. We first studied the topography of the developing LoC in
      the hindbrain, using as markers the key noradrenergic marker gene Dbh and the
      transcription factors Phox2a and Phox2b (upstream of Dbh). In both mouse and
      chicken, LoC neurons first appear arranged linearly along the middle one-third of
      the alar plate of rhombomere 1 (r1), collinear to a reference ventricular
      longitudinal band that early on expresses Phox2a and Phox2b in the alar plate of
      r2 and later expands to r1. Double-labeling experiments with LoC markers (Dbh or
      Phox2a) and either alar (Pax7 and Rnx3) or basal (Otp) genetic markers suggested
      that LoC cells migrate from their origin in the alar plate to a final position in
      the lateral basal plate. To corroborate these suggestions experimentally and
      determine the precise origin of the LoC, we fate mapped the LoC in the chick at
      stage HH11 by using quail-chick homotopic grafts. The experimental results
      confirmed that the LoC originates in the alar plate throughout the rostrocaudal
      extent of r1 and ruled out a rostrocaudal translocation. They also corroborated a
      ventralward tangential migration of LoC cells into the lateral basal plate, where
      the postmigratory LoC primordium is located. Comparisons with neighboring alar r1
      derived cell populations established that LoC neurons originate outside the
      cerebellum, in a matrix area intercalated dorsoventrally between the sources of
      the prospective vestibular and trigeminal columns.

PMID- 16628618
TI  - Distribution of hyaluronan in the central nervous system of the frog.
AB  - The qualitative and quantitative distribution pattern of hyaluronan (HA), a
      component of the extracellular matrix (ECM), was studied in the frog central
      nervous system by using a highly specific HA probe and digital image analysis. HA
      reaction was observed in both the white and the gray matter, showing a very
      intense staining around the perikarya and dendrites in the perineuronal net (PN).
      In the telencephalon, strong reaction was found in different parts of the
      olfactory system, in the pallium, and in the amygdala. In the diencephalon,
      intensive staining was found in the nucleus of Bellonci, the dorsal habenula, the
      lateral and central thalamic nuclei, and the subependymal zone of the third
      ventricle. In the mesencephalon, layers of optic tectum displayed different
      intensities, with the strongest reaction in layers B, D, F, 3, and 5. Other
      structures of the mesencephalon showed regional differences. The PN was
      especially intensively stained around the perikarya of the toral nuclei, the
      oculomotor and trochlear nuclei, and the basal optic nucleus. In the
      rhombencephalon, the granular layer of cerebellum, the vestibulocochlear nuclei,
      the superior olive, the spinal tract of the trigeminal nerve, and parts of the
      reticular formation showed the most intense reaction in the PN. In the spinal
      cord, considerable HA staining was found in the white matter and around the
      perikarya of motoneurons. The present study is the first description of the HA
      positive areas of frog brain and spinal cord demonstrating the heterogeneity of
      HA distribution in the frog central nervous system.

PMID- 16628619
TI  - N-methyl-D-aspartate receptor subunit phenotypes of vagal afferent neurons in
      nodose ganglia of the rat.
AB  - Most vagal afferent neurons in rat nodose ganglia express mRNA coding for the NR1
      subunit of the heteromeric N-methyl-D-aspartate (NMDA) receptor ion channel. NMDA
      receptor subunit immunoreactivity has been detected on axon terminals of vagal
      afferents in the dorsal hindbrain, suggesting a role for presynaptic NMDA
      receptors in viscerosensory function. Although NMDA receptor subunits (NR1, NR2B,
      NR2C, and NR2D) have been linked to distinct neuronal populations in the brain,
      the NMDA receptor subunit phenotype of vagal afferent neurons has not been
      determined. Therefore, we examined NMDA receptor subunit (NR1, NR2B, NR2C, and
      NR2D) immunoreactivity in vagal afferent neurons. We found that, although the
      left nodose contained significantly more neurons (7,603), than the right (5,978),
      the proportions of NMDA subunits expressed in the left and right nodose ganglia
      were not significantly different. Immunoreactivity for NMDA NR1 subunit was
      present in 92.3% of all nodose neurons. NR2B immunoreactivity was present in
      56.7% of neurons; NR2C-expressing nodose neurons made up 49.4% of the total
      population; NR2D subunit immunoreactivity was observed in just 13.5% of all
      nodose neurons. Double labeling revealed that 30.2% of nodose neurons expressed
      immunoreactivity to both NR2B and NR2C, whereas NR2B and NR2D immunoreactivities
      were colocalized in 11.5% of nodose neurons. NR2C immunoreactivity colocalized
      with NR2D in 13.1% of nodose neurons. Our results indicate that most vagal
      afferent neurons express NMDA receptor ion channels composed of NR1, NR2B, and
      NR2C subunits and that a minority phenotype that expresses NR2D also expresses
      NR1, NR2B, and NR2C.

PMID- 16628620
TI  - Dynein light chain Tctex-1 identifies neural progenitors in adult brain.
AB  - The identity and biology of stem cells and progenitors in the adult brain are of
      considerable interest, because these cells hold great promise for the development
      of novel therapies for damaged brain tissue in human diseases. This research
      field critically needs biological markers that specifically identify the resident
      precursors in the germinal zones of the adult central nervous system so that the
      discovery of regulatory influences for adult neurogenesis may be facilitated. In
      this study, by using a combination of in situ hybridization, bromodeoxyuridine
      incorporation, immunocolocalization, and ultrastructural studies, we show that in
      rodents Tctex-1, a cytoplasmic dynein light chain, is selectively enriched in
      almost all cycling progenitors and young neuronal progeny, but not in mature
      granular cells and astrocytes, in the subgranular zone of the adult dentate
      gyrus. Tctex-1 is also selectively abundant in cells closely resembling
      previously described immature progenitors and migrating neuroblasts at the
      subventricular zone of the lateral ventricle. Our results suggest that Tctex-1
      serves as a novel marker for the identification of neural progenitors of the
      adult brain.

PMID- 16628621
TI  - Expression of the glycinergic system during the course of embryonic development
      in the mouse spinal cord and its co-localization with GABA immunoreactivity.
AB  - To understand better the role of glycine and gamma-aminobutyric acid (GABA) in
      the mouse spinal cord during development, we previously described the ontogeny of
      GABA. Now, we present the ontogeny of glycine-immunoreactive (Gly-ir) somata and
      fibers, at brachial and lumbar levels, from embryonic day 11.5 (E11.5) to
      postnatal day 0 (P0). Spinal Gly-ir somata appeared at E12.5 in the ventral horn,
      with a higher density at the brachial level. They were intermingled with numerous
      Gly-ir fibers reaching the border of the marginal zone. By E13.5, at the brachial
      level, the number of Gly-ir perikarya sharply increased throughout the whole
      ventral horn, whereas the density of fibers declined in the marginal zone. In the
      dorsal horn, the first Gly-ir somata were then detected. From E13.5 to E16.5, at
      the brachial level, the density of Gly-ir cells remained stable in the ventral
      horn, and after E16.5 it decreased to reach a plateau. In the dorsal horn, the
      density of Gly-ir cells increased, and after E16.5 it remained stable. At the
      lumbar level, maximum expression was reached at E16.5 in both the ventral and
      dorsal horn. Finally, the co-localization of glycine and GABA was analyzed, in
      the ventral motor area, at E13.5, E15.5, and E17.5. The results showed that,
      regardless of developmental stage studied, one-third of the stained somata co
      expressed GABA and glycine. Our data show that the glycinergic system matures 1
      day later than the GABAergic system and follows a parallel spatiotemporal
      evolution, leading to a larger population of glycine cells in the ventral horn.

PMID- 16628622
TI  - Analysis of non-radial interneuron migration dynamics and its disruption in
      Lis1+/- mice.
AB  - Cell migration is an integral process in neural development. Analyses of radial
      cell migration (RCM) have revealed three modes of migration and specific defects
      in migration in various mouse mutants. In contrast, the dynamics of non-radial
      cell migration (NRCM) are incompletely understood. To investigate the dynamics of
      NRCM, we utilized a slice culture assay coupled with time-lapse videomicroscopy.
      This analysis revealed that non-radially migrating cells have a complex pattern
      of extending and retracting one or multiple processes while the nucleus advances
      concurrently or independently. These data indicate that the process of
      interneuron migration is unique to that seen for any mode of RCM. Non-radially
      migrating neurons moved for an average of 0.85 microm/min and paused for
      approximately 14% of the time observed. Given the novel morphology of NRCM, we
      hypothesized that specific aspects of migration would be defective with mutations
      in known cell migration genes, as described for RCM. This was tested by examining
      the dynamics of migration in the Lis1 mutant mouse; a well-defined cell migration
      mutant with known defects in NRCM. In contrast to wild-type cells, the rate of
      nuclear movement was significantly reduced in Lis1+/- interneurons, whereas the
      rate of active leading edge movement was similar. Morphologically, the leading
      process was significantly longer and the number of branches reduced in Lis1+/-
      mice. Together, these data indicate that the NRCM defect in Lis1+/- mice affects
      specific cellular processes. These data provide insight into NRCM and practical
      methods for future studies on the role(s) of specific genes in interneuron
      migration.

PMID- 16628623
TI  - Fine structural description of the lateral ocellus of Craterostigmus tasmanianus
      Pocock, 1902 (Chilopoda: Craterostigmomorpha) and phylogenetic considerations.
AB  - The lateral lens eye of adult Craterostigmus tasmanianus Pocock, 1902 (a
      centipede from Australia and New Zealand) was examined by light and electron
      microscopy. An elliptical, bipartite eye is located frontolaterally on either
      side of the head. The nearly circular posterior part of the eye is characterized
      by a plano-convex cornea, whereas no corneal elevation is visible in the
      crescentic anterior part. The so-called lateral ocellus appears cup-shaped in
      longitudinal section and includes a flattened corneal lens comprising a
      homogeneous and pigmentless epithelium of cornea-secreting cells. The retinula
      consists of two kinds of photoreceptive cells. The distribution of the distal
      retinula cells is highly irregular. Variable numbers of cells are grouped
      together in multilayered, thread-like unions extending from the ventral and
      dorsal margins into the center of the eye. Around their knob-like or bilobed
      apices the distal retinula cells give rise to fused polymorphic rhabdomeres. Both
      everse and inverse cells occur in the distal retinula. Smaller, club-shaped
      proximal retinula cells are present in the second (limited to the peripheral
      region) and proximal third of the eye, where they are arranged in dual cell
      units. In its apical region each unit produces a small, unidirectional rhabdom of
      interdigitating microvilli. All retinula cells are surrounded by numerous sheath
      cells. A thin basal lamina covers the whole eye cup, which, together with the
      distal part of the optic nerve, is wrapped by external pigment cells filled with
      granules of varying osmiophily. The eye of C. tasmanianus seemingly displays very
      high complexity compared to many other hitherto studied euarthropod eyes. Besides
      the complex arrangement of the entire retinula, the presence of a bipartite eye
      cup, intraocellar exocrine glands, inverse retinula cells, distal retinula cells
      with bilobed apices, separated pairs of proximal retinula cells, medio-retinal
      axon bundles, and the formation of a vertically partitioned, antler-like distal
      rhabdom represent apomorphies of the craterostigmomorph eye. These characters
      therefore collectively underline the separate position of the Craterostigmomorpha
      among pleurostigmophoran centipedes. The remaining retinal features of C.
      tasmanianus agree with those known from other chilopod eyes and, thus, may be
      considered plesiomorphies. Characters like the unicorneal eye cup, sheath cells,
      and proximal rhabdomeres with interdigitating microvilli were already present in
      the ground pattern of the Pleurostigmophora. Other retinal features were
      developed in the ancestral lineage of the Phylactometria (e.g., large elliptical
      eyes, external pigment cells, polygonal sculpturations on the corneal surface).
      The homology of all chilopod eyes (including Notostigmophora) is based
      principally on the possession of a dual type retinula.

PMID- 16628624
TI  - Immunocytochemistry of the neuromuscular systems of Loxosomella vivipara and L.
      parguerensis (Entoprocta: Loxosomatidae).
AB  - Little detailed information exists on the anatomy of the nervous system and the
      musculature of Entoprocta. Herein we describe the distribution of the
      neurotransmitters RFamide and serotonin as well as the myo-anatomy of adults and
      asexually produced budding stages of the solitary entoproct species Loxosomella
      vivipara and L. parguerensis using immunocytochemistry and epifluorescence as
      well as confocal microscopy. The development of the RFamidergic and serotonergic
      nervous system starts in early budding stages. In the adults, RFamide is present
      in the bilateral symmetric cerebral ganglion, a pair of oral nerves that
      innervate two pairs of nerve cell clusters in the heel of the foot, a pair of
      aboral nerves, the paired lateral nerves, the calyx nerves, the atrial ring
      nerve, the tentacle nerves, the stomach nerves, and the rectal nerves. Serotonin
      is only found in the cerebral ganglion, the oral nerves, and in the tentacle
      nerves. Some differences in the distribution of both neurotransmitters were found
      between L. vivipara and L. parguerensis and are most obvious in the differing
      number of large serotonergic perikarya associated with the oral nerves. Nerves
      arising from the cerebral ganglion and running in a ventral direction have not
      been described for Entoprocta before, and the homology of these to the ventral
      nerve cords of other Spiralia is considered possible. The body musculature of
      both Loxosomella species comprises longitudinal and diagonal muscles in the foot,
      the stalk, and the calyx. We found several circular muscles in the calyx. The
      stalk and parts of the foot and the calyx are surrounded by a fine outer layer of
      ring muscles. In addition to the congruent details regarding the myo-anatomy of
      both species, species-specific muscle structures could be revealed. The
      comparison of our data with recent findings of the myo-anatomy of two Loxosoma
      species indicates that longitudinal and diagonal body muscles, atrial ring
      muscles, tentacle muscles, esophageal and rectal ring muscles, as well as
      intestinal and anal sphincters are probably part of the ancestral entoproct
      muscle bauplan.

PMID- 16628625
TI  - A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg
      positive chronic hepatitis B.
AB  - Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a
      phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days
      were well tolerated, and produced significant antiviral activity. The present
      study was conducted to assess the degree and durability of the antiviral response
      to 12 weeks of clevudine treatment, and to investigate its safety and
      tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were
      randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34)
      groups. Patients were followed up after 12 weeks of treatment for a further 24
      weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at
      week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg
      clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment
      antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week
      12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the
      30- and 50-mg clevudine groups, respectively. Median serum alanine
      aminotransferase (ALT) levels decreased markedly from baseline during clevudine
      treatment and were maintained below the upper limit of normal throughout the 24
      weeks off-therapy in the two clevudine-treated groups. The incidences of adverse
      events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar
      for the three groups. In conclusion, clevudine showed potent antiviral activity
      during therapy and induced a sustained posttreatment antiviral effect for 6
      months after a 12-week treatment period, and this was associated with a sustained
      normalization of ALT levels.

PMID- 16628626
TI  - Genomic response to interferon-alpha in chimpanzees: implications of rapid
      downregulation for hepatitis C kinetics.
AB  - The mechanism of the interferon-alpha (IFN-alpha)-induced antiviral response
      during hepatitis C virus (HCV) therapy is n o t completely understood. In this
      study,we examined the transcriptional response to IFN-alpha in uninfected
      chimpanzees after single doses of chimpanzee, human, or human-pegylated IFN
      alpha. Liver and peripheral blood mononuclear cell (PBMC) samples were used for
      total genome microarray analysis. Most induced genes achieved maximal response
      within 4 hours, began to decline by 8 hours, and were at baseline levels by 24
      hours postinoculation, a time when high levels of circulating pegylated IFN-alpha
      were still present. The rapid downregulation of the IFN-alpha response may be
      involved in the transition between the observed phase I and phase II viral
      kinetics during IFN-alpha therapy in HCV-infected patients. The response to all
      three forms of IFN-alpha was similar; thus, the reasons for previous failures in
      antiviral treatment of chimpanzees with human IFN-alpha were not due to species
      specificity of IFN-alpha. The response to IFN-alpha was partially tissue
      specific. A total of 1778 genes were altered in expression by twofold or more by
      IFN-alpha, with 538 and 950 being unique to the liver or PBMC, respectively.
      Analysis of the IFN-alpha and IFN-gamma responses in primary chimpanzee and human
      hepatocytes were compared as well. IFN-alpha and IFN-gamma induced partially
      overlapping sets of genes in hepatocytes. In conclusion, the response to IFN
      alpha is largely tissue-specific, and the response is rapidly downregulated in
      vivo, which may have a significant influence on the kinetics of antiviral
      response.

PMID- 16628627
TI  - Identification of a hepatitis C virus-reactive T cell receptor that does not
      require CD8 for target cell recognition.
AB  - Hepatitis C virus (HCV) has been reported to elicit B and T cell immunity in
      infected patients. Despite the presence of antiviral immunity, many patients
      develop chronic infections leading to cirrhosis, hepatocellular carcinoma, and
      liver failure that can require transplantation. We have previously described the
      presence of HLA-A2-restricted, HCV NS3-reactive cytotoxic T lymphocytes (CTL) in
      the blood of HLA-A2- liver transplantation patients that received an HLA-A2+
      liver allograft. These T cells are analogous to the "allospecific" T cells that
      have been described in hematopoietic stem cell transplantation patients. It has
      been speculated that allospecific T cells express high-affinity T cell receptors
      (TCRs). To determine if our HCV-reactive T cells expressed TCRs with relatively
      high affinity for antigen, we identified and cloned a TCR from an allospecific
      HLA-A2-restricted, HCV:NS3:1406-1415-reactive CD8+ T cell clone and expressed
      this HCV TCR in Jurkat cells. Tetramer binding to HCV TCR-transduced Jurkat cells
      required CD8 expression, whereas antigen recognition did not. In conclusion,
      based on the reactivity of the TCR-transduced Jurkat cells, we have identified a
      TCR that transfers anti-HCV reactivity to alternate effectors. These data suggest
      this high affinity HCV-specific TCR might have potential new immunotherapic
      implications.

PMID- 16628628
TI  - Differential liver sensitization to toll-like receptor pathways in mice with
      alcoholic fatty liver.
AB  - Gut-derived, endotoxin-mediated hepatocellular damage has been postulated to play
      a crucial role in the pathogenesis of alcohol-induced liver injury in rodents.
      Endotoxins induce production of tumor necrosis factor alpha (TNF-alpha) by
      Kupffer cells via Toll-like receptor (TLR) 4 and contribute to liver injury. This
      study addressed the contribution of other TLRs and ligands to alcoholic fatty
      liver. C57Bl6/J mice were fed a modified Lieber-DeCarli diet. Serum
      aminotransferase measurements, histological analysis, and quantification of liver
      TNF-alpha and TLR1-9 messenger RNA (mRNA) were performed. The effect of TLR
      ligands on liver injury was assessed in vivo. Neomycin and metronidazole or
      diphenyleneiodonium sulfate (DPI) were administered to evaluate the role of gut
      bacteria and NADPH oxidase activity, respectively, in hepatic TLR expression.
      Enteral ethanol (EtOH) exposure induced steatosis and increased liver weight,
      aminotransferase levels, and expression of TLR1, 2, 4, 6, 7, 8, and 9 liver mRNA.
      Injection of lipoteichoic acid, peptidoglycan (PGN), lipopolysaccharide (LPS),
      loxoribine, and oligonudeotide containing CpG (ISS-ODN) increased TNF-alpha mRNA
      expression more in the livers of EtOH-fed mice than in control mice. PGN, LPS,
      flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but
      not control mice. Addition of antibiotics reduced the severity of alcoholic fatty
      liver without affecting TLR expression, whereas daily DPI injections reduced the
      EtOH-mediated upregulation of TLR2, 4, 6, and 9 mRNA. In conclusion, EtOH-fed
      mice exhibited an oxidative stress dependent on upregulation of multiple TLRs in
      the liver and are sensitive to liver inflammation induced by multiple bacterial
      products recognized by TLRs.

PMID- 16628629
TI  - Altered hepatobiliary gene expressions in PFIC1: ATP8B1 gene defect is associated
      with CFTR downregulation.
AB  - Recent reports in patients with PFIC1 have indicated that a gene defect in ATP8B1
      could cause deregulations in bile salt transporters through decreased expression
      and/or activity of FXR. This study aimed to: (1) define ATP8B1 expression in
      human hepatobiliary cell types, and (2) determine whether ATP8B1 defect affects
      gene expressions related to bile secretion in these cells. ATP8B1 expression was
      detected by RT-PCR in hepatocytes and cholangiocytes isolated from normal human
      liver and gallbladder. ATP8B1 mRNA levels were 20- and 200-fold higher in bile
      duct and gallbladder epithelial cells, respectively, than in hepatocytes. RT-PCR
      analyses of the liver from two patients with PFIC1, one with PFIC2, one with
      biliary atresia, showed that, compared to normal liver, hepatic expressions of
      FXR, SHP, CYP7A1, ASBT were decreased at least by 90% in all cholestatic
      disorders. In contrast, NTCP transcripts were less decreased (by < or = 30% vs.
      97%) in PFIC1 as compared with other cholestatic disorders, while BSEP
      transcripts, in agreement with BSEP immunohistochemical signals, were normal or
      less decreased (by 50% vs. 97%). CFTR hepatic expression was decreased (by 80%),
      exclusively in PFIC1, while bile duct mass was not reduced, as ascertained by
      cytokeratin-19 immunolabeling. In Mz-ChA-2 human biliary epithelial cells, a
      significant decrease in CFTR expression was associated with ATP8B1 invalidation
      by siRNA. In conclusion, cholangiocytes are a major site ofATP8B1 hepatobiliary
      expression. A defect of ATP8B1 along with CFTR downregulation can impair the
      contribution of these cells to bile secretion, and potentially explain the
      extrahepatic cystic fibrosis-like manifestations that occur in PFIC1.

PMID- 16628631
TI  - Nasobiliary drainage for cholestatic pruritus.

PMID- 16628632
TI  - Adeno-associated virus-mediated expression of apolipoprotein (a) kringles
      suppresses hepatocellular carcinoma growth in mice.
AB  - Hepatocellular carcinoma (HCC) constitutes more than 90% of all primary liver
      cancers. HCC is a hypervascular tumor that develops from dedifferentiation of
      small avascular HCC and is therefore a good target for anti-angiogenic gene
      therapy. Recent studies have identified apolipoprotein(a) [apo(a)] kringles LK68
      and LK8 (LKs) as having a potential antiangiogenic and anti-tumor activity, and
      the current study evaluates the therapeutic potential of gene therapy with
      recombinant adeno-associated virus carrying genes encoding LKs (rAAV-LK) in the
      treatment of hypervascular HCC. We generated rAAV-LK to obtain persistent
      transgene expression in vivo, which is essential for anti-angiogenic therapy. The
      rAAV-produced LKs substantially inhibited proliferation and migration of human
      umbilical vein endothelial cells (HUVECs) in vitro, validating their anti
      angiogenic potential. Intramuscular administration of rAAV-LK gave 60% to 84%
      suppression (P < .05) of tumor growth in mice bearing subcutaneously transplanted
      HCC derived from Huh-7 and Hep3B cells, respectively. Histological and
      immunohistochemical analyses of HCC tumor sections showed that a single
      administration of rAAV-LK gave rise to persistent expression of LKs that
      inhibited tumor angiogenesis and triggered tumor apoptosis, and, thus,
      significantly suppressed tumor growth. The administration of rAAV-LK provided a
      significant survival benefit (P < .05), and 3 of 10 rAAV-LK-treated mice were
      still alive without visible tumors and without clinical symptoms 188 days after
      treatment. In conclusion, rAAV-LK is a potential candidate for anti-angiogenic
      gene therapy in the treatment of HCC.

PMID- 16628633
TI  - Progressive histological damage in liver allografts following pediatric liver
      transplantation.
AB  - The long-term histological outcome after pediatric liver transplantation (OLT) is
      not yet fully understood. De novo autoimmune hepatitis, consisting of
      histological chronic hepatitis associated with autoantibody formation and
      allograft dysfunction, is increasingly recognized as an important complication of
      liver transplantation, particularly in the pediatric population. In this study,
      158 asymptomatic children with 5-year graft survival underwent protocol liver
      biopsies (113, 135, and 64 at 1, 5, and 10 years after OLT, respectively).
      Histological changes we re correlated with dinical,biochemical, and serological
      findings. All patients received cydosporine A as primary immunosuppression with
      withdrawal of corticosteroids at 3 months post OLT. Normal or near-normal
      histology was reported in 77 of 113 (68%), 61 of 135 (45%), and 20 of 64 (31%) at
      1, 5, and 10 years, respectively. The commonest histological abnormality was
      chronic hepatitis (CH), the incidence of which increased with time [25/113 (22%),
      58/135 (43%), and 41/64 (64%) at 1, 5, and 10 years, respectively) (P < .0001)].
      The incidence of fibrosis associatedwith CH increasedwith time [13/25 (52%),
      47/58 (81%), and 37/41 (91%) at 1, 5, and 10 years, respectively) (P < .0001)].
      The severity of fibrosis associated with CH also increased with time, such that
      by 10 years 15% had progressed to cirrhosis. Aspartate aminotransfemse (AST)
      levels were slightly elevated in children with CH (median levels 52 IU/L, 63
      IU/L, and 48 IU/L at 1, 5, and 10 years, respectively), but this did not reach
      statistical significance compared with those with normal histology. On
      multivariate analysis, the only factor predictive of chronic hepatitis was
      autoantibody positivity (present in 13% and 10% of children with normal biopsies
      at 5 and 10 years, respectively, and 72% and 80% of those with CH at 5 and 10
      years, respectively) (P < .0001). Four children with CH and autoantibodies, who
      also had raised immunoglobulin G (IgG) levels and AST greater than 1.5 x normal
      fulfilled the diagnostic criteria for de novo autoimmune hepatitis (AIH). Another
      two were found to be hepatitis C positive. No definite cause for CH could be
      identified in the other cases. In condusion, chronic hepatitis is a common
      finding in children after liver transplantation and is associated with a high
      risk of developing progressive fibrosis, leading to cirrhosis. Standard liver
      biochemical tests cannot be relied on either in the diagnosis or in the
      monitoring of progress of chronic allograft hepatitis. In contrast, the presence
      ofautoantibodies is strongly associated with the presence of CH. The cause of
      chronic hepatitis in transplanted allografts is uncertain but may be immune
      mediated, representing a hepatitic form of chronic rejection.

PMID- 16628634
TI  - Id1 is a critical mediator in TGF-beta-induced transdifferentiation of rat
      hepatic stellate cells.
AB  - Transforming growth factor (TGF)-beta is critically involved in the activation of
      hepatic stellate cells (HSCs) that occurs during the process of liver damage, for
      example, by alcohol, hepatotoxic viruses, or aflatoxins. Overexpression of the
      TGF-beta antagonist Smad7 inhibits transdifferentiation and arrests HSCs in a
      quiescent stage. Additionally, bile duct ligation (BDL)-induced fibrosis is
      ameliorated by introducing adenoviruses expressing Smad7 with down-regulated
      collagen and alpha-smooth muscle actin (alpha-SMA) expression. The aim of this
      study was to further characterize the molecular details of TGF-beta pathways that
      control the transdifferentiation process. In an attempt to elucidate TGF-beta
      target genes responsible for fibrogenesis, an analysis of Smad7-dependent mRNA
      expression profiles in HSCs was performed, resulting in the identification of the
      inhibitor of differentiation 1 (Id1) gene. Ectopic Smad7 expression in HSCs
      strongly reduced Id1 mRNA and protein expression. Conversely, Id1 overexpression
      in HSCs enhanced cell activation and circumvented Smad7-dependent inhibition of
      transdifferentiation. Moreover, knock-down of Id1 in HSCs interfered with alpha
      SMA fiber formation, indicating a pivotal role of Id1 for fibrogenesis. Treatment
      of HSCs with TGF-beta1 led to increased Id1 protein expression, which was not
      directly mediated by the ALK5/Smad2/3, but the ALK1/Smad1 pathway. In vivo, Id1
      expression and Smad1 phosphorylation were co-induced during fibrogenesis. In
      conclusion, Id1 is identified as TGF-beta/ALK1/Smad1 target gene in HSCs and
      represents a critical mediator of transdifferentiation that might be involved in
      hepatic fibrogenesis. Supplementary material for this article can be found on the
      HEPATOLOGY website (http://interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 16628635
TI  - Thermoreversible gelation polymer induces the emergence of hepatic stem cells in
      the partially injured rat liver.
AB  - Focal injury of the adult liver causes formation of granulomatous tissue and
      fibrosis. When thermoreversible gelation polymer (TGP) was applied to such
      defects of the rat liver, complete recovery of hepatic tissues was observed
      without granulation. We analyzed the mechanism of the regeneration. TGP is a
      chemically synthesized biocompatible polymer material whose sol-gel transition is
      reversible by changing the temperature. Cooled TGP was poured into a penetration
      lesion of the rat liver. Immunohistochemistry and polymerase chain reaction were
      carried out using tissues and cultured cells isolated from ductular structures.
      Immunocytochemical and ultrastructural analyses were also conducted. Seven days
      after TGP treatment, ductular reactions were observed around the wound and
      ductules elongated to the injured area. Cells in the structures were alpha
      fetoprotein (AFP) positive, albumin+, CK19+, c-Kit+, and Thyl+. Hepatocyte-like
      cells possessing glycogen appeared around the tips of the ductules from day 9.
      The defect was completely replaced with hepatocytes by day 28. Cells isolated
      from the ductules expressed Musashi-1, c-Kit, Thyl, AFP, albumin, transferrin,
      connexin 43, and CK19. When the cultured cells were covered by TGP, they rapidly
      proliferated to form colonies, whereas without TGP cells gradually died.
      Morphologically and ultrastructurally the cells were similar to hepatocytes. They
      expressed not only albumin and transferrin but TAT, CYP2E1, and CCAAT/enhancer
      binding protein a. Some cells formed bile canaliculus-like structures. In
      conclusion, TGP may trigger the initiation of hepatic stem cells in biliary
      ductules, and stem cell activation may occur even in the regeneration of the
      normal liver.

PMID- 16628636
TI  - Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell
      growth in vitro and in vivo.
AB  - The pituitary tumor transforming (PTTG) gene family comprises PTTG1, 2, and 3.
      Forced expression of PTTG1 (securin) induces cellular transformation and promotes
      tumor development in animal models. PTTG1 is overexpressed in various human
      cancers. However, the expression and pathogenic implications of the PTTG gene
      family in hepatocellular carcinoma are largely unknown. Gene silencing using
      short interfering RNA (siRNA) has become an efficient means to study the
      functions of genes and has been increasingly used for cancer gene therapy
      approaches. We report that PTTG1, but not PTTG2 and 3, was highly and frequently
      expressed in liver cancer tissues from patients and highly in SH-J1, SK-Hep1, and
      Huh-7 hepatoma cell lines. Adenoviral vector encoding siRNA against PTTG1
      (Ad.PTTG1-siRNA) depleted PTTG1 specifically and efficiently in SH-J1 hepatoma
      cells, which resulted in activation of p53 that led to increased p21 expression
      and induction of apoptosis. The depletion of PTTG1 in HCT116 colorectal cancer
      cells exhibited a cytotoxic effect in a p53-dependent manner. Ad.PTTG1-siRNA
      mediated cytotoxic effect was dependent on expression levels of PTTG1 and p53 in
      hepatoma cell lines. Huh-7 hepatoma cells, once transduced with Ad.PTTG1-siRNA,
      displayed markedly attenuated growth potential in nude mice. Intra-tumor delivery
      of Ad.PTTG1-siRNA led to significant inhibition of tumor growth in SH-J1 tumor
      xenograft established in nude mice. In conclusion, PTTG1 overexpressed in
      hepatoma cell lines negatively regulates the ability of p53 to induce apoptosis.
      PTIG1 gene silencing using siRNA may be an effective modality to treat liver
      cancer, in which PTTG1 is abundantly expressed. Supplementary material for this
      article can be found on the HEPATOLOGY website
      (http://interscience.wiley.com/jpages/0270-9139/ suppmat/index.html).

PMID- 16628637
TI  - Elevated serum alanine aminotransferase activity and calculated risk of coronary
      heart disease in the United States.
AB  - In the United States, elevated serum alanine aminotransferase (ALT) activity in
      the absence of viral hepatitis or excessive alcohol consumption is most commonly
      attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD is related to
      predictors of coronary heart disease (CHD) such as insulin resistance and central
      obesity. We examined the association between elevated serum ALT activity and the
      10-year risk of CHD as estimated using the Framingham risk score (FRS). We
      performed a cross-sectional analysis comparing participants in the Third National
      Health and Nutrition Examination Survey with normal and elevated ALT activity
      (>43 IU/L), examining the mean levels of FRS. Among participants without viral
      hepatitis or excessive alcohol consumption, those with elevated ALT activity
      (n=267) had a higher FRS than those with normal ALT activity (n=7259), both among
      men (mean difference in FRS 0.25, 95% CI 0.07-0.4; hazard ratio for CHD 1.28, 95%
      CI 1.07-1.5) and women (mean difference in FRS 0.76, 95% CI 0.4-1.1; hazard ratio
      for CHD 2.14, 95% CI 1.5-3.0). The ALT threshold for increased risk of CHD was
      higher in men (>43 IU/L) than in women (>30 IU/L). Elevated ALT activity was not
      associated with higher FRS among nonobese participants with viral hepatitis or
      excessive alcohol consumption. In condusion, individuals with elevated serum ALT
      activity in the absence of viral hepatitis or excessive alcohol consumption, most
      of whom have NAFLD, have an increased calculated risk of CHD. This association is
      more prominent in women.

PMID- 16628638
TI  - Association between postprandial LDL conjugated dienes and the severity of liver
      fibrosis in NASH.

PMID- 16628639
TI  - Hepatitis C databases, principles and utility to researchers.
AB  - Part of the effort to develop hepatitis C-specific drugs a nd vaccines is the
      study of genetic variability of allpublicly available HCV sequences. Three HCV
      databases are currently available to aid this effort and to provide additional
      insight into the basic biology, immunology, and evolution of the virus. The
      Japanese HCV database (http://s2as02.genes.nig.ac.jp) gives access to a genomic
      mapping of sequences as well as their phylogenetic relationships. The European
      HCV database (http://euhcvdb.ibcp.fr) offers access to a computer-annotated set
      of sequences and molecular models of HCV proteins and focuses on protein
      sequence, structure and function analysis. The HCV database at the Los Alamos
      National Laboratory in the United States (http://hcv.lanl.gov) provides access to
      a manually annotated sequence database and a database of immunological epitopes
      which contains concise descriptions of experimental results. In this paper, we
      briefly describe each of these databases and their associated websites and tools,
      and give some examples of their use in furthering HCV research.

PMID- 16628640
TI  - Duration of peginterferon therapy in acute hepatitis C: a randomized trial.
AB  - Spontaneous resolution of acute hepatitis C virus infection cannot be predicted,
      and chronic evolution of the disease occurs in a majority of cases. To assess the
      efficacy and safety of peginterferon alpha-2b administered for 8, 12, or 24 weeks
      in patients with acute hepatitis C virus infection a total of 161 patients were
      identified with acute hepatitis C virus infection. Of these, 30 patients refused
      treatment but were retained in the study as a nonrandomized comparison group. Of
      the 131 patients who consented to treatment, 29 patients spontaneously resolved,
      leaving 102 patients randomly assigned to peginterferon alpha-2b (1.5 microg/kg)
      for 8 weeks (group A; n=34), 12 weeks (group B; n=34), and 24 weeks (group C;
      n=34). The primary end point was sustained virologic response. An intent-to-treat
      analysis was used for efficacy and safety end points. Sustained virologic
      response was achieved in 23/34 (67.6%), 28/34 (82.4%), and 31/34 (91.2%) of
      patients in groups A, B, and C, respectively; all had undetectable hepatitis C
      virus RNA 48 weeks after the end of therapy. Treatment for 8 or 12 weeks was
      effective in genotypes 2, 3, and 4, whereas genotype 1 required 24 weeks of
      therapy. The 8- and 12-week regimens were associated with fewer adverse events
      compared with the 24-week regimen. In conclusion, peginterferon alpha-2b
      effectively induces high sustained virologic response rates in patients with
      acute hepatitis C virus infection, thus preventing development of chronic
      hepatitis C. Duration of treatment should be further optimized based on genotype
      and rapid virologic response at week 4.

PMID- 16628641
TI  - Correlation of initial autoantibody profile and clinical outcome in primary
      biliary cirrhosis.
AB  - Although there have been significant advances in understanding the clinical and
      biochemical features of primary biliary cirrhosis (PBC), there is still a paucity
      of data on the usefulness of biomarkers as prognostic indicators. This is
      particularly important at the time of initial diagnosis. Indeed, the widespread
      use of antimitochondrial antibody testing has led to an earlier diagnosis of
      asymptomatic PBC and it is difficult to predict which patients will experience a
      benign versus a rapidly progressive course. To address this issue, we examined a
      unique population of 127 newly diagnosed patients with PBC during a 15-year
      period of observation that began in January 1990. Sera from these patients were
      analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies,
      and immunoblotting was performed for nuclear pore complex (NPC). The patients
      were then followed up longitudinally using biochemical liver function tests. No
      patient was under any medical therapy for PBC at the time of the initial sera
      collection. Data were analyzed based not only on the clinical features, but also
      the Mayo score and specific outcome measures, including time to death, need for
      liver transplantation, and complication free survival. Among patients with early
      disease, bilirubin increased to >2 mg/dL in the anti-NPC(+) patients (26% vs. 5%,
      P = .019). Anti-NPC antibodies remained stable or slightly increased over the
      period of observation. In condusion, anti-NPC identifies patients likely to
      experience an unfavorable clinical course and more rapid disease progression.

PMID- 16628642
TI  - Correlation between insulin resistance and hepatitis C viral load.

PMID- 16628643
TI  - Effects of angiogenic factor overexpression by human and rodent cholangiocytes in
      polycystic liver diseases.
AB  - Liver involvement in autosomal dominant polycystic kidney disease (ADPKD) is
      characterized by altered remodeling of the embryonic ductal plate (DP) with
      presence of biliary cysts and aberrant portal vasculature. The genetic defect
      causing ADPKD has been identified, but mechanisms of liver cyst growth remain
      uncertain. To investigate the possible role of angiogenic mechanisms, we have
      studied the immunohistochemical expression of vascular endothelial growth factor
      (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and their receptors (VEGFR
      1, VEGFR-2, Tie-2) in ADPKD, Caroli's disease, normal and fetal livers. In ADPKD
      and control livers Ang-1 and Ang-2 gene expression was studied by real-time-PCR.
      Effects of VEGF on cholangiocyte proliferation were studied by PCNA Western Blot
      in isolated rat cholangiocytes and by MTS assay in cultured cholangiocytes
      isolated from ADPKD patients and from an ADPKD mouse model (Pkd2(WS25/-)).
      Cholangiocytes were strongly positive for VEGF, VEGFR-1, VEGFR-2 and Ang-2 in
      ADPKD and Caroli, and also for Ang-1 and Tie-2 in ADPKD, similar to fetal ductal
      plate cells. VEGF stimulated proliferation in both normal and ADPKD
      cholangiocytes, but the effect was particularly evident in the latter. Ang-1
      alone had no effect, but was synergic to VEGF. VEGF expression on cholangiocytes
      positively correlated with microvascular density. In conclusion, consistent with
      the immature phenotype of the cystic epithelium, expression of VEGF, VEGFRs, Ang
      1 and Tie-2 is strongly upregulated in cholangiocytes from polycystic liver
      diseases. VEGF and Ang-1 have autocrine proliferative effect on cholangiocyte
      growth and paracrine effect on portal vasculature, thus promoting the growth of
      the cysts and their vascular supply. Supplementary material for this article can
      be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 16628644
TI  - Assessment of biliary fibrosis by transient elastography in patients with PBC and
      PSC.
AB  - Noninvasive measurement of liver stiffness with transient elastography has been
      recently validated for the evaluation of hepatic fibrosis in chronic hepatitis C.
      The current study assessed the diagnostic performance of liver stiffness
      measurement (LSM) for the determination of fibrosis stage in chronic cholestatic
      diseases. One hundred one patients with primary biliary cirrhosis (PBC, n=73) or
      primary sclerosing cholangitis (PSC, n=28) were prospectively enrolled in a
      multicenter study. All patients underwent liver biopsy (LB) and LSM. Histological
      and fibrosis stages were assessed on LB by two pathologists. LSM was performed by
      transient elastography. Efficiency of LSM for the determination of histological
      and fibrosis stages were determined by a receiver operating characteristics (ROC)
      curve analysis. Analysis failed in six patients (5.9%) because of unsuitable LB
      (n=4) or LSM (n=2). Stiffness values ranged from 2.8 to 69.1 kPa (median, 7.8
      kPa). LSM was correlated to both fibrosis (Spearman's rho= 0.84, P < .0001) and
      histological (0.79, P < .0001) stages. These correlations were still found when
      PBC and PSC patients were analyzed separately. Areas under ROC curves were 0.92
      for fibrosis stage (F) > or =2, 0.95 for F > or =3 and 0.96 for F=4. Optimal
      stiffness cutoff values of 7.3, 9.8, and 17.3 kPa showed F > or =2, F > or =3 and
      F=4, respectively. LSM and serum hyaluronic acid level were independent
      parameters associated with extensive fibrosis on LB. In conclusion, transient
      elastography is a simple and reliable noninvasive means for assessing biliary
      fibrosis. It should be a promising tool to assess antifibrotic therapies in PBC
      or PSC.

PMID- 16628645
TI  - Prevention of first overt episode of hepatic encephalopathy after TIPS: no easy
      task.

PMID- 16628647
TI  - Antiproliferative effects of interferon alpha on hepatic progenitor cells in
      vitro and in vivo.
AB  - Hepatic progenitor cells (called oval cells in rodents) proliferate during
      chronic liver injury. They have been suggested as targets of malignant
      transformation in chronic liver diseases, including chronic hepatitis C.
      Interferon alpha therapy reduces the risk of hepatocellular carcinoma (HCC) in
      chronic hepatitis C regardless of viral clearance. The aim of this study was to
      determine whether interferon alpha could reduce the risk of HCC by modifying
      preneoplastic events in the hepatic progenitor cell population. Pre- and post
      treatment liver biopsies were evaluated for changes in t he hepaticprogenitor
      cell population in 16 patients with non-responding chronic hepatitis C Interferon
      alpha-based treatment significantly reduced the numbers of c-kit-positive hepatic
      progenitor cells by 50%. To determine the mechanism of cell number reduction, the
      effects of interferon alpha on murinehepatic progenitor cells were studied in
      vitro. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
      proliferation assay and proliferating cell nuclear antigen staining showed that
      interferon alpha had a dose-dependent, anti-proliferative effect Interferon alpha
      stimulated hepatocytic and biliary differentiation of the oval cell lines
      reflected by increased expression of albumin and cytokeratin19 accompanied by
      decreased expression of alphafetoprotein and Thy-1. To validatethese results in
      vivo, mice were placed on the choline-deficient, ethionine-supplemented diet to
      induce liver injury and oval cell proliferation and treated with pegylated
      interferon alpha 2b for 2 weeks. This resulted in a significant four-fold
      reduction in the number of oval cells (P < .05). In conclusion, interferon alpha
      based treatment reduced the number of hepatic progenitor cells in chronic liver
      injury by modulating apoptosis, proliferation, and differentiation. Supplementay
      material for this article can

PMID- 16628648
TI  - Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with
      hepatopulmonary syndrome.
AB  - Enhanced pulmonary production of nitric oxide (NO) has been implicated in the
      pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with N(G)-nitro-L
      arginine methyl ester (L-NAME) in both animals and humans with HPS has improved
      arterial hypoxemia. We assessed the role of enhanced NO production in the
      pathobiology of arterial deoxygenation in HPS and the potential therapeutic
      efficacy of selective pulmonary NO inhibition. We investigated the effects of
      nebulized L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and
      extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS
      (60 +/- 7 [SD] yr; alveolar-arterial oxygen gradient, range 19-76 mm Hg; arterial
      oxygen tension, range 37-89 mm Hg). Nebulized L-NAME maximally decreased exhaled
      NO (by -55%; P < .001), mixed venous nitrite/nitrate (by -12%; P = .02), and
      cardiac output (by -11%; P = .002) while increased systemic vascular resistance
      (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In
      contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn,
      arterial deoxygenation remained unchanged. In conclusion, gas exchange
      disturbances in HPS may be related to pulmonary vascular remodeling rather than
      to an ongoing vasodilator effect of enhanced NO production.

PMID- 16628650
TI  - BRAF mutations in colorectal carcinoma suggest two entities of microsatellite
      unstable tumors.

PMID- 16628652
TI  - Estrogen-based hormone therapy and thrombosis risk in women with essential
      thrombocythemia.
AB  - BACKGROUND: There is currently insufficient evidence to either support or refute
      an association between estrogen-based hormone treatment (EBHT) and thrombosis
      risk in essential thrombocythemia (ET). METHODS: A retrospective review of
      thrombotic events, which occurred both at diagnosis of ET and during subsequent
      follow-up, was performed in a consecutive cohort of women with WHO-defined ET
      seen at the Mayo Clinic. Details of EBHT were concomitantly obtained. RESULTS: A
      total of 305 women were seen during the study period and followed for a median of
      133 months. EBHT at diagnosis was documented in 59 women and such therapy was
      instituted at a variable time after diagnosis in 34 additional patients. At
      diagnosis, major thrombosis occurred in 73 patients (24%), including 11 of 59
      (19%) on EBHT and 62 of 246 (25%) not on EBHT (P=.28). Thrombosis after diagnosis
      occurred in 94 patients (31%), including 64 of 212 (30%) not on EBHT, 5 of 17
      (29%) in whom EBHT was discontinued at diagnosis, 13 of 42 (31%) in whom EBHT was
      continued despite the diagnosis of ET, and 12 of 34 (35%) in whom EBHT was
      started after diagnosis (P=.95). The overall results were the same when arterial
      and venous events were analyzed separately. However, EBHT in the form of oral
      contraceptives (OCP) was associated with an increased risk of venous thrombosis
      (P=.03). CONCLUSIONS: EBHT is safe in ET outside the setting of OCP use, which
      might be associated with an increased risk of deep vein thrombosis.

PMID- 16628653
TI  - Notch-1 down-regulation by curcumin is associated with the inhibition of cell
      growth and the induction of apoptosis in pancreatic cancer cells.
AB  - BACKGROUND: Notch signaling plays a critical role in maintaining the balance
      between cell proliferation, differentiation, and apoptosis, and thereby may
      contribute to the development of pancreatic cancer. Therefore, the down
      regulation of Notch signaling may be a novel approach for pancreatic cancer
      therapy. It has been reported that curcumin down-regulates many genes that are
      known to promote survival and also up-regulates genes that are known promoters of
      apoptosis in pancreatic cancer cells in vitro. It also has been reported that
      there is cross-talk between Notch-1 and another major cell growth and apoptotic
      regulatory pathway, the nuclear factor kappaB (NF-kappaB) pathway, which is down
      regulated by both curcumin and reduction of Notch-1 levels. However, to the
      authors' knowledge to date, no studies have determined whether the down
      regulation of Notch-1 signaling, resulting in the inactivation of NF-kappaB
      activity, contributes to curcumin-induced cell growth inhibition and apoptosis in
      pancreatic cancer cells. METHODS: The authors used multiple molecular approaches,
      such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay, an apoptosis assay, gene transfection, real-time reverse transcriptase
      polymerase chain reaction analysis, Western blot analysis, and an electrophoretic
      mobility shift assay to measure the DNA binding activity of NF-kappaB. RESULTS:
      Curcumin inhibited cell growth and induced apoptosis in pancreatic cancer cells.
      Notch-1, Hes-1, and Bcl-XL expression levels concomitantly were down-regulated by
      curcumin treatment. These results correlated with the inactivation of NF-kappaB
      activity and increased apoptosis induced by curcumin. The down-regulation of
      Notch-1 by small-interfering RNA prior to curcumin treatment resulted in enhanced
      cell growth inhibition and apoptosis. CONCLUSIONS: The current results provide
      the first demonstration to the authors' knowledge that the Notch-1 signaling
      pathway is associated mechanistically with NF-kappaB activity during curcumin
      induced cell growth inhibition and apoptosis of pancreatic cells. These results
      suggest that the down-regulation of Notch signaling by curcumin may be a novel
      strategy for the treatment of patients with pancreatic cancer.

PMID- 16628654
TI  - Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients
      with fever and neutropenia: a pilot study of 40 patients based on validated risk
      prediction rules.
AB  - BACKGROUND: The objective of this study was to assess the feasibility of empiric,
      oral, outpatient quinolone monotherapy in 40 adult patients with fever and
      neutropenia who were at low risk for serious medical complications. METHODS:
      Patients with breast cancer or sarcoma who presented with fever and neutropenia
      and were identified as low risk received empiric, oral, quinolone monotherapy
      (gatifloxacin at a dose of 400 mg once daily). Patients who had a significant
      source/focus of infection on presentation were excluded. After an initial
      observation period of 4 to 8 hours in the emergency center, the remainder of
      their management was ambulatory. Patients were evaluated for response to therapy,
      development of complications and/or the need for hospital admission, and drug
      related adverse events. RESULTS: Three of 43 patients studied were ineligible
      medically because of the presence of Common Toxicity Criteria (version 3.0)
      Grade>2 mucositis. Of the 40 eligible patients, 38 patients (95%) responded to
      gatifloxacin monotherapy, although 1 patient requested hospital admission (92%
      response for ambulatory management). The mean duration of therapy was 7 days, and
      the median number of days from enrollment to defervescence was 4 days. There were
      no serious medical complications, no drug-related adverse events, and no deaths
      on study or during 30 days of follow-up. CONCLUSIONS: The results from this study
      indicated that outpatient quinolone monotherapy in low-risk febrile neutropenic
      patients is safe, effective, and well received. These conclusions need to be
      validated in a randomized trial.

PMID- 16628655
TI  - Diagnostic utility of mucin profile in fine-needle aspiration specimens of the
      pancreas: an immunohistochemical study with surgical pathology correlation.
AB  - BACKGROUND: The cytologic differentiation between neoplastic and
      reactive/reparative processes in the endoscopic ultrasound-guided fine-needle
      aspirations (EUS-FNA) of the pancreas can be difficult. Malignant transformation
      of the pancreatic ductal epithelium changes the expression of apomucins. The goal
      of the current study was to determine an optimal immunohistochemical panel of
      mucin (MUC) antibodies that would allow the cytomorphologic distinction of
      pancreatic ductal adenocarcinoma and its differentiation from reactive/reparative
      processes and inadvertently sampled gastric and duodenal mucosa. METHODS:
      Pancreatic EUS-FNA specimens performed on 351 patients were reviewed. Expression
      profiles of MUC1, 2, 5AC, and 6 were examined on 56 cell block sections and 26
      follow-up pancreatectomy specimens. RESULTS: MUC1 and 6 expression was found in
      nonneoplastic pancreatic samples, whereas there was an absence of expression of
      MUC2 and 5AC. MUC2 was detected in mucosal goblets cells of the duodenum, MUC6 in
      Brunner glands, and MUC5AC in gastric foveolar cells. MUC5AC expression in
      differentiating ductal adenocarcinomas from benign conditions demonstrated better
      operating characteristics than either MUC1 or MUC6. The apomucin expression
      pattern both in cytology and follow-up surgical pathology specimens was similar.
      In surgical pathology specimens, the panel of 3 antibodies, MUC1+/MUC2-/MUC5AC+,
      was noted in 15 of 17 ductal carcinomas (88.2%). In nonneoplastic pancreatic
      tissue, the expression panel MUC1+/MUC2-/MUC5AC- was observed in 14 of 17 (82.4%)
      cases. In cytology specimens, the combination of MUC1+/MUC2-/MUC5AC+ was noted in
      21 of 30 ductal carcinoma cases (70.0%), 3 of 6 atypical cases (50%), and 1 of 1
      suspicious for malignancy cases (100%). The combination MUC1+/MUC2-/MUC5AC+ was
      not observed in any of the negative for malignancy or reactive cases (0 of 6).
      CONCLUSIONS: The most optimal panel for the diagnosis of ductal adenocarcinoma in
      both the EUS-FNA specimens is a panel including MUC1/MUC2/MUC5AC, whereas a panel
      of all 4 antibodies (MUC1, 2, 5AC, and 6) will in addition aid in differentiating
      inadvertently sampled normal/reactive duodenal and gastric epithelium from
      neoplastic pancreatic tissue.

PMID- 16628656
TI  - The PapSpin: a reasonable alternative to other, more expensive liquid-based
      Papanicolaou tests.
AB  - BACKGROUND: This study was designed to optimize a liquid-based Papanicolaou (Pap)
      test by using common cytopathology laboratory equipment and resulted in an
      inexpensive test that was equivalent at least diagnostically to the conventional
      Papanicolaou (Pap) smear. METHODS: Adult women (n = 482) were consented,
      enrolled, and included in this Institutional Review Board-approved study. After
      conventional Pap smear slides were obtained, clinicians placed the collection
      device with residual cells from the uterine cervix in a preservative fluid. In
      the cytopathology laboratory, a conventional centrifuge device was used to
      deposit the cells from the liquid onto a glass slide. RESULTS: Among the
      conventional Pap smears, 43 were categorized as low-grade squamous
      intraepithelial lesions (LSIL), and 30 were categorized as high-grade squamous
      intraepithelial lesions or greater (HSIL+). Among the PapSpin samples, 49 were
      categorized as LSIL and 24 were categorized as HSIL+. Biopsy confirmation was
      obtained in 124 patients. There were 23 women diagnosed with LSIL and 27 women
      diagnosed with HSIL+. Diagnostic agreement between cytologic samples and biopsies
      is as follows: for conventional Pap smears, there was agreement on 11 of 23 LSIL
      diagnoses and on 15 of 27 HSIL+ diagnoses; for PapSpin samples, there was
      agreement on 11 of 23 LSIL diagnoses and on 14 of 27 HSIL+ diagnoses. Exact
      agreement was achieved between PapSpin and conventional smears in 404 patients
      (84%). Quality indictors were better in the PapSpin group, except for inadequate
      endocervical component, which was greater in the PapSpin samples, a difference
      that was explained by the split-sample study design, which favored the
      conventional smear. CONCLUSIONS: The current results indicated that PapSpin is a
      legitimate, inexpensive alternative to the conventional Pap smear for the
      detection of cervical intraepithelial neoplasia, resulting in better preservation
      and improved cell visualization. In addition, the liquid residual allows for
      reflex human papillomavirus-DNA or polymerase chain reaction testing.

PMID- 16628657
TI  - Update on peripheral nerve microsurgery.

PMID- 16628658
TI  - Neuroanatomy of the brachial plexus: the missing link in the continuity between
      the central and peripheral nervous systems.
AB  - The brachial plexus is a complex network of nerves which extends from the neck to
      the axilla and which supplies motor, sensory, and sympathetic fibers to the upper
      extremity. Generally it is formed by the union of the ventral primary rami of the
      spinal nerves, C5-C8 and T1, the so-called "roots" of the brachial plexus. The
      goal here is to examine the neural architecture of the brachial plexus. The most
      constant arrangement of nerve fibers will be delineated, and then the predominant
      variations in neural architecture will be defined, particularly the prefixed and
      postfixed plexus, as well as the microanatomy and anatomy of the major terminal
      branches of the plexus. Multiple tracts connect many parts of the nervous system,
      and multiple ascending and descending tracts connect the peripheral nervous
      system (PNS) and lower spinal centers with the brain. This reflects that the
      nervous system is able to extract different pieces of sensory information from
      its surroundings and encode them separately, and that it is able to control
      specific aspects of motor behavior using different sets of neurons. Examination
      of the major sensory or motor pathways reveals a highly and tightly organized
      nervous system. In particular, at each of many levels, we see fairly exact maps
      of the world within the brain. In an effort to understand the functional
      neuroanatomy of the brachial plexus, this paper will focus briefly on the nervous
      connections of the nerves of the upper extremity with the brain. The goal here is
      to better understand "what the brain sees" after nerve injury and repair.

PMID- 16628659
TI  - Repair of the main nerve trunk of the upper limb with end-to-side neurorrhaphy:
      an experimental study in rabbits.
AB  - The aim of this study was to assess the effectiveness of reinnervation using end
      to-side neurorrhaphy in the upper extremity of the rabbit. The cut right ulnar
      nerve was repaired and sutured to the side of the median nerve about 3 cm above
      the elbow joint. The extent of reinnervation was quantitatively evaluated, as
      well as the integrity of the intact donor nerve in 36 rabbits randomly treated
      with fresh or delayed nerve repair with or without perineurotomy. Evaluations
      included nerve conduction velocity (NCV) of both the ulnar and medial nerves, dry
      muscle weight, and histologic examination (neurofilament stain and morphometric
      assessment) at 3 and 6 months postoperatively. NCV recovery rates were 79% and
      87% for the ulnar nerve, and 89% and 94% for the median nerve compared to
      contralateral intact nerves, at 3 and 6 months, respectively. Flexor carpi
      ulnaris muscle mass measurements revealed a recovery in dry muscle weight of
      about 81% and 88% at 3 and 6 months, respectively, compared to the intact
      contralateral flexor carpi ulnaris. Histologic studies with neurofilament
      staining reveal numerous axonal sprouts at the distal end of the median nerve,
      indicative of myelinated axonal regeneration. Morphometric analysis demonstrated
      no difference between fresh and delayed repairs. These results indicate that in
      the upper extremity of rabbits, end-to-side neurorrhaphy permits axonal
      regeneration from the intact donor nerve, and is associated with satisfactory
      recovery. The effect of the procedure on the donor nerve was negligible.

PMID- 16628661
TI  - Application of lentivirus-mediated RNAi in studying gene function in mammalian
      tooth development.
AB  - RNA interference (RNAi) has recently become a powerful tool to silence gene
      expression in mammalian cells, but its application in assessing gene function in
      mammalian developing organs remains highly limited. Here we describe several
      unique developmental properties of the mouse molar germ. Embryonic molar
      mesenchyme, but not the incisor mesenchyme, once dissociated into single cell
      suspension and re-aggregated, retains its odontogenic potential, the capability
      of a tissue to instruct an adjacent tissue to initiate tooth formation.
      Dissociated molar mesenchymal cells, even after being plated in cell culture,
      retain odontogenic competence, the capability of a tissue to respond to
      odontogenic signals and to support tooth formation. Most interestingly, while
      dissociated epithelial and mesenchymal cells of molar tooth germ are mixed and re
      aggregated, the epithelial cells are able to sort out from the mesenchymal cells
      and organize into a well-defined dental epithelial structure, leading to the
      formation of a well-differentiated tooth organ after sub-renal culture. These
      unique molar developmental properties allow us to develop a strategy using a
      lentivirus-mediated RNAi approach to silence gene expression in dental
      mesenchymal cells and assess gene function in tooth development. We show that
      knockdown of Msx1 or Dlx2 expression in the dental mesenchyme faithfully
      recapitulates the tooth phenotype of their targeted mutant mice. Silencing of
      Barx1 expression in the dental mesenchyme causes an arrest of tooth development
      at the bud stage, demonstrating a crucial role for Barx1 in tooth formation. Our
      studies have established a reliable and rapid assay that would permit large-scale
      analysis of gene function in mammalian tooth development.

PMID- 16628663
TI  - Progress on the action plan for liver disease research.

PMID- 16628664
TI  - Signal transduction cascades and hepatitis B and C related hepatocellular
      carcinoma.

PMID- 16628665
TI  - HCV and lipoproteins: is oxLDL an Achilles' heel of the Trojan horse?

PMID- 16628666
TI  - Polycystic liver disease: new insights into disease pathogenesis.

PMID- 16628667
TI  - Tailoring antiviral therapy in hepatitis C.

PMID- 16628668
TI  - Hepatopulmonary syndrome: more than just a matter of tone?

PMID- 16628669
TI  - Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of
      iatrogenic and biological factors.
AB  - In Egypt, schistosomiasis was traditionally the most important public health
      problem and infection with Schistosoma mansoni the major cause of liver disease.
      From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook
      large control campaigns using intravenous tartar emetic, the standard treatment
      for schistosomiasis, as community-wide therapy. This commendable effort to
      control a major health problem unfortunately established a very large reservoir
      of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral
      drug, praziquantel, replaced tartar emetic a s treatment f o r schistosomiasis in
      the entire country. This both reduced schistosomal transmission and disease and
      interrupted the "occult" HCV epidemic. It was evident when diagnostic serology
      became available in the 1990s that HCV had replaced schistosomiasis as the
      predominant cause of chronic liver disease. Epidemiological studies reported a
      high prevalence and incidence of HCV, particutarly within families in rural areas
      endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with
      chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co
      infections with schistosomiasis caused more severe liver disease than infection
      with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV
      specific T-cell responses leading to increased viral load, a higher probability
      of HCV chronicity, and more rapid progression of complications in co-infected
      persons. As complications of HCV usually occur after 20 years of infection, the
      peak impact of the Egyptian outbreak has not yet occurred. Efforts have been
      initiated by the Egyptian MOH to prevent new infections and complications of HCV
      in the estimated 6 million infected persons.

PMID- 16628670
TI  - Oxidized low-density lipoprotein inhibits hepatitis C virus cell entry in human
      hepatoma cells.
AB  - Cell entry of hepatitis C virus, pseudoparticles (HCVpp) and cell culture grown
      virus (HCVcc), requires the interaction of viral glycoproteins with CD81 and
      other as yet unknown cellular factors. One of these is likely to be the scavenger
      receptor class B type I (SR-BI). To further understand the role of SR-BI, we
      examined the effect of SR-BI ligands on HCVpp and HCVcc infectivity. Oxidized low
      density lipoprotein (oxLDL), but not native LDL, potently inhibited HCVpp and
      HCVcc cell entry. Pseudoparticles bearing unrelated viral glycoproteins or bovine
      viral diarrhea virus were not affected. A dose-dependent inhibition was observed
      for HCVpp bearing diverse viral glycoproteins with an approximate IC50 of 1.5
      microg/mL apolipoprotein content, which is within the range of oxLDL reported to
      be present in human plasma. The ability of lipoprotein components to bind to
      target cells associated with their antiviral activity, suggesting a mechanism of
      action which targets a cell surface receptor critical for HCV infection of the
      host cell. However, binding of soluble E2 to SR-BI or CD81 was not affected by
      oxLDL, suggesting that oxLDL does not act as a simple receptor blocker. At the
      same time, oxLDL incubation altered the biophysical properties of HCVpp,
      suggesting a ternary interaction of oxLDL with both virus and target cells. In
      conclusion, the SR-BI ligand oxLDL is a potent cell entry inhibitor for a broad
      range of HCV strains in vitro. These findings suggest that SR-BI is an essential
      component of the cellular HCV receptor complex.

PMID- 16628671
TI  - Early identification of HCV genotype 1 patients responding to 24 weeks
      peginterferon alpha-2a (40 kd)/ribavirin therapy.
AB  - Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a
      sustained virological response (SVR) after 24 weeks of treatment with
      peginterferon alpha-2a (40 kd) plus ribavirin in a randomized, multinational
      trial. We aimed to identify factors associated with a rapid virological response
      (RVR) at week 4 (HCV RNA <50 IU/mL) and a SVR (HCV RNA <50 IU/mL at the end of
      follow-up) in these patients. Stepwise multiple logistic regression analysis was
      used to explore the prognostic factors for a RVR and SVR in genotype 1 patients
      treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week
      treatment groups had a RVR. SVR rates were considerably higher in patients with
      than without [corrected] a RVR (89% vs. 19%, respectively). Patients with a
      baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5; P < .0001)
      or 200,000-600,000 IU/mL (OR 5.6, 95% CI 1.5-9.1; P = .0057) were more likely to
      achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b
      vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7; P =
      .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than
      200,000 IU/mL (OR 2.7 vs. > 600,000 IU/mL, 95% CI 1.1-6.3; P < .026) were
      significant and independent predictors of SVR in patients treated for 24 weeks.
      In conclusion, patients infected with HCV genotype 1 and treated with
      peginterferon alpha-2a/ribavirin sustained a RVR 24% of the time. This portends
      an 89% probability of a SVR after 24 weeks of treatment.

PMID- 16628672
TI  - Mrp4-/- mice have an impaired cytoprotective response in obstructive cholestasis.
AB  - Mrp4 is a member of the multidrug resistance-associated gene family that is
      expressed on the basolateral membrane of hepatocytes and undergoes adaptive
      upregulation in response to cholestatic injury or bile acid feeding. However, the
      relative importance of Mrp4 in a protective adaptive response to cholestatic
      injury is not known. To address this issue, common bile duct ligation (CBDL) was
      performed in wild-type and Mrp4-/- mice and animals followed for 7 days.
      Histological analysis and serum aminotransferase levels revealed more severe
      liver injury in the absence of Mrp4 expression. Western analyses revealed that
      Mrp4, but not Mrp3, was significantly increased after CBDL in wild-type mice.
      Serum bile acid levels were significantly lower in Mrp4-/- mice than in wild-type
      CBDL mice, whereas serum bilirubin levels were the same, suggesting that Mrp4 was
      required to effectively extrude bile acids from the cholestatic liver. Mrp3 and
      Ostalpha-Ostbeta were upregulated in Mrp4-/- mice but were unable to compensate
      for the loss of Mrp4. High-performance liquid chromatography analysis on liver
      extracts revealed that taurine tetrahydroxy bile acid/beta-muricholic acid ratios
      were increased twofold in Mrp4-/- mice. In conclusion, hepatic Mrp4 plays a
      unique and essential protective role in the adaptive response to obstructive
      cholestatic liver injury.

PMID- 16628673
TI  - Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver
      transplantation in Mdr2+/- mice.
AB  - Intrahepatic bile duct strictures are a serious complication after orthotopic
      liver transplantation (OLT). We examined the role of endogenous bile salt
      toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type
      mice and mice heterozygous for disruption of the multidrug resistance 2 Mdr2 gene
      (Mdr2+/-) were transplanted into wild-type recipient mice. Mdr2+/- mice secrete
      only 50% of the normal amount of phospholipids into their bile, leading to an
      abnormally high bile salt/phospholipid ratio. In contrast to homozygous Mdr2-/-
      mice, the Mdr2+/- mice have normal liver histology and function under normal
      conditions. Two weeks after OLT, bile duct injury and cholestasis were assessed
      by light and electron microscopy, as well as through molecular and biochemical
      markers. There were no signs of bile duct injury or intrahepatic cholestasis in
      liver grafts from wild-type donors. Liver grafts from Mdr2+/- donors, however,
      had enlarged portal tracts with cellular damage, ductular proliferation,
      biliostasis, and a dense inflammatory infiltrate after OLT. Parallel to this
      observation, recipients of Mdr2+/- livers had significantly higher serum
      transaminases, alkaline phosphatase, total bilirubin, and bile salt levels, as
      compared with recipients of wild-type livers. In addition, hepatic bile
      transporter expression was compatible with the biochemical and histological
      cholestatic profile found in Mdr2+/- grafts after OLT. In conclusion, toxic bile
      composition, due to a high biliary bile salt/phospholipid ratio, acted
      synergistically with cold ischemia in the pathogenesis of bile duct injury after
      transplantation.

PMID- 16628674
TI  - A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of
      patients with primary biliary cirrhosis and pruritus.
AB  - A single nucleotide polymorphism characterized by the substitution of valine for
      glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was
      found in a group of patients with primary biliary cirrhosis. This heterozygous
      mutation was significantly associated with the presence of pruritus.

PMID- 16628675
TI  - Association between mixed cryoglobulinemia, translocation (14;18), and
      persistence of occult HCV lymphoid infection after treatment.

PMID- 16628676
TI  - Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary
      obstruction.
AB  - Renal function in the course of obstructive jaundice has been the subject of
      great interest; however, little is known about the expression of renal organic
      anion transporters. The objective of this work was to study, in rats with acute
      extrahepatic cholestasis, the cortical renal expression of the organic anion
      transporter 1 (OAT1) and the organic anion transporter 3 (OAT3), in association
      with the pharmacokinetics and renal excretion of furosemide (FS). Male Wistar
      rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served
      as controls. All studies were carried out 21 hours after surgery. Rats were
      anesthetized and the pharmacokinetic parameters of FS and the renal elimination
      of FS were determined. Afterwards, the kidneys were excised and processed for
      immunoblot (basolateral membrane and renal homogenates) or immunocytochemical
      (light microscopic and confocal immunofluorescence microscopic analysis)
      techniques. The systemic and renal clearance of FS as well as the excreted and
      secreted load of FS increased in BDL rats. In kidneys from BDL rats,
      immunoblotting showed a significant increase in the abundance of both OAT1 and
      OAT3 in homogenates from renal cortex. In basolateral membranes from kidney
      cortex of BDL rats, OATI abundance was also increased and OAT3 abundance was not
      modified. Immunocytochemical techniques confirmed these results. In conclusion,
      acute obstructive jaundice is associated with an upregulation of OAT1 and OAT3,
      which might explain, at least in part, the increased systemic and renal
      elimination of FS.

PMID- 16628677
TI  - Solid-state IR-LD spectroscopic and theoretical analysis of arginine-containing
      peptides.
AB  - Structural prediction and IR-characteristic bands assignment of arginine
      containing tri- and tetrapeptides glycyl-glycyl-arginine (GGArg) and glycyl
      glycyl-arginyl-alanine (GGArgAla) have been carried out, using linear-dichroic
      infrared (IR-LD) spectroscopy of oriented solid-samples in a nematic liquid
      crystal suspension. Spectroscopic data have been supported with ab initio
      analysis (Hartree-Fock level of theory and 6-31++G** basis set). Predicted
      geometry parameters have been compared with known crystallographic ones of
      similar peptides, indicating a good correlation.

PMID- 16628678
TI  - Overcoming language barriers in medical care.

PMID- 16628679
TI  - Classification of human liver transplant recipients by their preoperative CD8+ T
      cell subpopulation and its relation to outcome.
AB  - The primed status of T cells is markedly different among liver transplant
      recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by
      aging, and diseases. This study aims to characterize the preoperative
      immunological status of CD8+ T cell subpopulations and relate it to the outcome
      for liver transplant recipients. We classified 112 liver transplant recipients
      into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform
      proportion of T cells. In Groups I and II (pediatric), the naive T cell
      proportion was more than 50%. In adult recipients, Group III was characterized by
      a naive T cell proportion of 50%, Group IV had the greatest effector/memory T
      cells (EM), and Group V had the greatest proportion of effector T cells. In
      Groups IV and V, the effector T cell proportion was considerably higher, and was
      accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation
      of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin
      expression. Group V recipients tended to be complicated postoperatively, with a
      significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern
      Cooperative Oncology Group performance status.

PMID- 16628680
TI  - Outcomes and risk factors for failure of radiologic treatment of biliary
      strictures in pediatric liver transplantation recipients.
AB  - Posttransplantation biliary strictures occur in 5-34% of the pediatric liver
      transplant patients and are conventionally managed by interventional radiological
      techniques. The aim of this manuscript is to assess the outcomes of patients with
      biliary strictures treated by percutaneous dilatation at our institution.
      Included in the study were 35 children with posttransplant biliary strictures
      that were treated with percutaneous dilatation and stenting. Initial dilation and
      biliary stent placement was accomplished in all patients without complications
      requiring surgical intervention. Recurrent strictures developed in 23 (66%) of 35
      patients. The recurrence rate was 45% for anastomotic strictures, 90% for
      intrahepatic strictures, and 100% for those with both an anastomotic and
      intrahepatic component. Seven patients required revision of the
      choledochojejunostomy, 5 of them with a successful outcome and 2 requiring
      retransplant. Five patients were treated with retransplantation without surgical
      revision. Patients with an intrahepatic or a "combined" stricture were less
      likely to have a successful outcome after radiologic treatment. In conclusion,
      the radiological treatment of biliary strictures with balloon dilation and
      stenting can be performed successfully with minimal complications avoiding the
      need for surgical correction in many cases.

PMID- 16628681
TI  - Immediate tracheal extubation following liver transplantation.

PMID- 16628682
TI  - Prophylactic strategies for hepatitis B patients undergoing liver transplant: a
      cost-effectiveness analysis.
AB  - Hepatitis B immunoglobulin with lamivudine prophylaxis (LAM/HBIG) is effective in
      preventing Hepatitis B (HBV) recurrence posttransplant but is expensive and
      inconvenient. Lamivudine-resistant HBV, which has limited the usefulness of
      lamivudine monoprophylaxis in transplant, can now be effectively controlled with
      adefovir dipivoxil. We performed a cost-effectiveness analysis on the strategies
      of lamivudine prophylaxis with adefovir rescue(LAM/ADV) compared to combination
      LAM/intravenous fixed high-dose HBIG prophylaxis(LAM/ivHBIG) or LAM/intramuscular
      HBIG prophylaxis(LAM/imHBIG). Markov modeling was performed with analysis from
      societal perspective. Probability rates were derived from systematic review of
      the literature and cost taken from MEDICARE database. Outcome measures were
      incremental cost-effectiveness ratio(ICER) and cost to prevent each HBV
      recurrence and death. Analysis was performed at 5 years posttransplant as well as
      at end of life expectancy (15 years). Combination LAM/ivHBIG cost an additional
      USD562,000 at 15 years, while LAM/imHBIG cost an additional USD139,000 per
      patient compared to LAM/ADV. Although there is an estimated increase in
      recurrence of 53% with LAM/ADV and 7.6% increased mortality at the end of life
      expectancy (15 years), the ICER of LAM/ivHBIG over LAM/ADV treatment is
      USD760,000 per quality-adjusted life-years and for LAM/imHBIG, USD 188,000. Cost
      effectiveness is most sensitive to cost of HBIG. Lamivudine prophylaxis with
      adefovir dipivoxil salvage offers the more cost-effective option for HBV patients
      undergoing liver transplant but with higher recurrence and death rate using a
      model that favors LAM/HBIG. Lowering the cost of HBIG maintenance will improve
      cost-effectiveness of LAM/HBIG strategy. In conclusion, a tailored approach based
      on individual risks will optimize the cost-benefit of HBV transplant prophylaxis.

PMID- 16628683
TI  - A model of donors' decision-making in adult-to-adult living donor liver
      transplantation in Japan: having no choice.
AB  - This study examined the decision-making processes of donors in adult-to-adult
      living donor liver transplantation. Twenty-two donors were interviewed using a
      semi-structured format. Interview contents were transcribed verbatim and analyzed
      qualitatively using grounded theory. A decision-making model was developed
      consisting of 5 stages: (1) recognition, (2) digestion, (3) decision-making, (4)
      reinforcement, and (5) resolution. The second and the third stages described
      donors' experiences of "reaching a decision"; the fourth and fifth stages
      described those of "facing transplantation." The central theme of this model was
      "having no choice," which consisted of 4 codes: (1) priority of life, (2) only
      LDLT, (3) for family, and (4) only me. In conclusion, this model can help health
      care professionals to understand the donor experience and, based on that
      understanding, to provide sufficient support to the donor.

PMID- 16628684
TI  - Bile duct strictures after liver transplantation: a changing landscape of the
      Achilles' heel.

PMID- 16628685
TI  - Auxiliary partial orthotopic living donor liver transplantation for a child with
      congenital absence of the portal vein.
AB  - Congenital absence of the portal vein (CAPV) is a rare malformation of the
      mesenteric vasculature in which visceral venous blood bypasses the liver,
      completely draining into the systemic circulation through a congenital porto
      systemic shunt. Liver transplantation has rarely been indicated for patients with
      this disease. We present a child with CAPV who was managed successfully by living
      donor auxiliary partial orthotopic liver transplantation (APOLT), while
      preserving the right lobe of the native liver. In conclusion, APOLT for patients
      with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is
      not necessary.

PMID- 16628687
TI  - Domino liver transplantation in maple syrup urine disease.
AB  - Liver transplantation has been reported in a few cases of maple syrup urine
      disease (MSUD), but is controversial. Many patients with approved indications for
      liver transplantation die before grafts are available. A 25-yr-old man with MSUD
      underwent liver transplantation, and his liver was used as a domino graft for a
      53-yr-old man with hepatocellular carcinoma who had low priority on the liver
      transplant waiting list and was unlikely to survive until routine organ
      procurement. Both transplants were performed as "piggy back" procedures,
      reconstructing the domino graft with caval segments from the cadaveric donor.
      Neither required veno-venous bypass. Whole body leucine oxidation was estimated
      by 13CO2 in breath after oral boluses of L-[1-13C]-leucine, before and after
      transplantation in both patients and a control subject. The surgical outcome was
      successful. The patient with MSUD had marked decreases in plasma branched-chain
      amino acids (BCAAs) and alloisoleucine (from 255 +/- 66 to 16 +/- 7 micromol/L),
      despite advancement of dietary protein from 6 to >40 gm/day. The domino recipient
      maintained near-normal levels of plasma amino acids with no detectable
      alloisoleucine on unrestricted diet. Leucine oxidation increased in the patient
      with MSUD (from 2.2 to 5.6% recovered in 4 hours) and decreased in the recipient
      (from 9.7 to 6.2%). Neither patient demonstrated any apparent symptoms of MSUD
      over more than 7 months. In conclusion, liver transplantation substantially
      corrects whole body BCAA metabolism in MSUD and greatly attenuates the disease.
      Livers from patients with MSUD may be considered as domino grafts for patients
      who might otherwise not survive until transplantation.

PMID- 16628689
TI  - Anastomotic biliary strictures after liver transplantation: causes and
      consequences.
AB  - We retrospectively studied the prevalence, presentation, results of treatment,
      and graft and patient survival of grafts developing an anastomotic biliary
      stricture (AS) in 531 adult liver transplantations performed between 1979 and
      2003. Clinical and laboratory information was obtained from the hospital files,
      and radiological studies were re-evaluated. Twenty-one possible risk factors for
      the development of AS (variables of donor, recipient, surgical procedure, and
      postoperative course) were analyzed in a univariate and stepwise multivariate
      model. Forty-seven grafts showed an anastomotic stricture: 42 in duct-to-duct
      anastomoses, and 5 in hepaticojejunal Roux-en-Y anastomoses. The cumulative risk
      of AS after 1, 5, and 10 years was 6.6%, 10.6%, and 12.3% respectively.
      Postoperative bile leakage (P = 0.001), a female donor/male recipient combination
      (P = 0.010), and the era of transplantation (P = 0.006) were independent risk
      factors for the development of an AS. In 47% of cases, additional (radiologically
      minor) nonanastomotic strictures were diagnosed. All patients were successfully
      treated by 1 or more treatment modalities. As primary treatment, endoscopic
      retrograde cholangiopancreaticography (ERCP) was successful in 24 of 36 (67%)
      cases and percutaneous transhepatic cholangiodrainage in 4 of 11 (36%). In the
      end 15 patients (32%) were operated, all with long-term success. AS presenting
      more than 6 months after transplantation needed more episodes of stenting by
      ERCP, and more stents per episode compared to those presenting within 6 months
      and recurred more often. Graft and patient survival were not impaired by AS.

PMID- 16628690
TI  - Outcome of patients with hepatitis B virus and human immunodeficiency virus
      infections referred for liver transplantation.
AB  - The outcome of patients with hepatitis B virus (HBV) and human immunodeficiency
      virus (HIV) referred for liver transplantation (LT) is unknown. A high frequency
      of lamivudine-resistant (LAM-R) HBV infection may increase the risk of liver
      related death pre-transplantation and prophylaxis failure post-transplantation.
      We evaluated the association of LAM-R HBV on pre-transplant survival and post
      transplant outcomes in 35 consecutive HIV-HBV coinfected patients referred for LT
      between July 2000 and September 2002. At the time of referral, the median CD4
      count was 273/mm, MELD was 14, and LAM-R HBV infection was present in 67%. Among
      these referred patients, 26% were listed, 29% not listed due to relative/absolute
      contraindications; 26% not listed as too early for LT; 9% not listed as too sick
      for LT; and 11% died during transplant evaluation. Of the 9 listed patients, 4
      remained listed, 1 died 18 months post-referral, and 4 were transplanted (11% of
      total) 3 to 40 months after listing. Of 17 evaluated but not listed patients, 5
      died (p=0.38 compared to listed group) and all deaths were liver-related. All the
      HBV-HIV coinfected patients, who were transplanted, are HBsAg negative and have
      undetectable HBV DNA levels on prophylactic therapy using hepatitis B immune
      globulin (HBIG) plus lamivudine, with and without tenofovir or adefovir, with
      median 33.1 months follow-up. Late referral and the presence of LAM-R HBV pre
      transplantation are common in referred HIV-HBV patients. In HIV-HBV coinfected
      patients undergoing LT, HBV recurrence is successfully prevented with combination
      prophylaxis using HBIG and antivirals.

PMID- 16628691
TI  - Isolated right hepatic vein obstruction after piggyback liver transplantation.
AB  - The "piggyback" technique for liver transplantation has gained worldwide
      acceptance. Still, complications such as outflow obstruction have been observed,
      usually attributable to technical errors such as small-caliber anastomosis of the
      suprahepatic vena cava, twisting, or kinking. Iatrogenic Budd-Chiari syndrome
      after piggyback liver transplantation has been reported as a consequence of
      obstruction involving the entire anastomosis (usually the 3 hepatic veins). Here
      we describe technical issues, clinical presentation, diagnosis, and treatment of
      3 cases in which outflow obstruction affected only the right hepatic vein. In
      conclusion, all 3 patients developed recurrent ascites requiring angioplasty
      and/or stent placement across the right hepatic vein to alleviate the symptoms.

PMID- 16628692
TI  - Biliary complications following adult right lobe ex vivo split liver
      transplantation.
AB  - Biliary complications are common following split liver transplantation (SLT). We
      analyzed the incidence, treatment, and outcome of biliary complications following
      adult right lobe ex vivo SLT performed between November 1992 and January 2005.
      There were 72 patients, of which 70 were analyzed. Early postoperative deaths
      resulted in 2 being excluded from the analysis. There were 44 males (median age,
      48 yr; range, 19-70 yr). Biliary reconstruction was by duct-to-duct (DD)
      anastomosis in 52 (74%) and Roux-en-Y hepaticojejunostomy (RYHJ) in 18 (26%)
      patients. Until mid-2001, no T-tube was used for DD anastomosis (DD/non-T-tube)
      in 26 (37%) patients; subsequent to this, DD over a T-tube (DD/T-tube) was
      performed in 26 (37%) patients. Eighteen (26%) biliary complications occurred in
      16 patients. Two anastomotic leaks of RYHJ were associated with hepatic artery
      thrombosis. The most frequent biliary complication was parenchymal radical leak
      from the transected liver surface (11%; 8/70), with anastomotic leaks in 6%
      (4/70) and strictures in 4% (3/70). There were also 2 cases of biliary leaks from
      T-tube exit site following T-tube removal, and 1 leak from the donor cystic duct
      stump. DD anastomosis without a T-tube was associated with a higher rate of cut
      surface and anastomotic biliary leaks (7/26), compared to the DD/T-tube group
      (1/26; P = 0.05). Six patients (9%) died following biliary complications,
      including 3 due to cut surface leaks in the DD/non-T-tube group and 2 cases with
      fatal biliary peritonitis following T-tube removal. A patient in the RYHJ group
      died due to biliary sepsis associated with hepatic artery thrombosis. In
      conclusion, biliary complications following right lobe ex vivo SLT are associated
      with significant morbidity and mortality. Our results suggest that T-tube biliary
      drainage of DD anastomosis may reduce parenchymal cut surface and biliary
      anastomotic leaks. However, bile leak following T-tube removal could lead to
      potentially fatal biliary peritonitis, which should always be anticipated and
      treated promptly.

PMID- 16628693
TI  - Development of pulmonary hypertension in 5 patients after pediatric living-donor
      liver transplantation: de novo or secondary?
AB  - The development of portopulmonary hypertension (PH) in a patient with end-stage
      liver disease is related to high cardiac output and hyperdynamic circulation.
      However, PH following liver transplantation is not fully understood. Of 617
      pediatric patients receiving transplants between June 1990 and March 2004, 5
      (median age 12 yr, median weight 24.5 kg) were revealed to have portopulmonary
      hypertension (PH) after living-donor liver transplantation (LDLT), as confirmed
      by echocardiography and/or right heart catheterization. All children underwent
      LDLT for post-Kasai biliary atresia. In 2 patients with refractory biliary
      complications, PH developed following portal thrombosis; 2 with stable graft
      function, who had had intrapulmonary shunting (IPS) before LDLT, were found to
      have PH in spite of overcoming liver dysfunction due to hepatitis. PH developed
      shortly after distal splenorenal shunting in 1 patient, who suffered liver
      cirrhosis due to an intractable outflow blockage. The onset of PH ranged from 2.8
      to 11 yr after LDLT, and mean pulmonary artery pressure (mPAP) estimated by
      echocardiography at the time of presentation ranged from 43 to 120 mmHg. Three of
      the 5 patients are alive under prostaglandin I2 (PGI2) treatment. Of these, 1 is
      prepared for retransplantation for an intractable complications of liver
      allograft, while the other 2 with satisfactory grafts are being considered for
      lung transplantation. Even after LDLT, PH can develop with portal hypertension.
      Periodic echocardiography is essential for early detection and treatment of PH
      especially in the recipients with portal hypertension not only preoperatively but
      also postoperatively.

PMID- 16628694
TI  - Impact of implementation of the MELD scoring system on the prevalence and
      incidence of chronic renal disease following liver transplantation.

PMID- 16628695
TI  - Bactobilia after liver transplantation: frequency and antibiotic susceptibility.
AB  - After liver transplantation (LT), bactobilia occurs frequently in patients,
      leading in some cases to cholangitis and biliary sepsis. The present study is the
      first to investigate bactobilia after LT, and it gives an overview of
      predisposing factors for bactobilia, the microbial spectrum in the bile of LT
      patients, and the antibiotic susceptibility. A total of 172 endoscopic retrograde
      cholangiography (ERC) procedures were performed in 66 LT patients between 1 month
      and 5.8 years after LT. Bile samples were examined microbiologically. Sixty-eight
      nontransplanted patients without cholestasis, but requiring ERC for other reasons
      served as a control group. Of 172 samples obtained from LT patients, 126 (73.3%)
      were positive for microbes. A total of 236 organisms were isolated: 114 (48.3%)
      gram-positive bacteria, 92 (39.0%) aerobic gram-negative, 8 (3.4%) anaerobes, and
      22 (9.3%) fungi. Ciprofloxacin and amoxycillin/clavulanic acid showed the best
      susceptibility results among oral antibiotics and piperacillin/tazobactam and
      imipenem/cilastatin among intravenous preparations. In contrast, only 15.7% of
      non-LT patients showed bactobilia. In conclusion, our study shows that bactobilia
      is a problem in patients after LT and that it is not only a contamination from
      endoscopic intervention. Mechanical obstruction, plastic stents, gallstones, and
      papillotomy increase the risk of bactobilia significantly. In our cohort we had
      the best antibiotic susceptibility results for positive cultures in LT patients
      with piperacillin/tazobactam, ciprofloxacin, or amoxycillin/clavulanic acid.

PMID- 16628696
TI  - Recurrent hepatitis C post-liver transplant: the lessons learned.

PMID- 16628697
TI  - Antifungal prophylaxis in liver transplant patients: a systematic review and meta
      analysis.
AB  - We performed a meta-analysis to determine whether antifungal prophylaxis
      decreases infectious morbidity and mortality in liver transplant patients. We
      searched for randomized trials dealing with prophylaxis with systemic antifungal
      agents. We used a fixed effect model, with risk ratio (RR) and 95% confidence
      interval (CI); we assessed study quality for heterogeneity and publication bias.
      Six studies (5 double-blind), for a total of 698 patients, compared fluconazole,
      itraconazole, or liposomal amphotericin to placebo (5 studies) or oral nystatin.
      Prophylaxis reduced colonization (RR, 0.45; CI, 0.37-0.55), total proven fungal
      infections (RR, 0.31; CI, 0.21-0.46), which included both superficial (RR, 0.27;
      CI, 0.16-0.45) and invasive (RR, 0.33; CI, 0.18-0.59) infections, and mortality
      attributable to fungal infection (RR, 0.30; CI, 0.12-0.75). Prophylaxis did not
      affect overall mortality (RR, 1.06; CI, 0.69-1.64) or empiric treatment for
      suspected fungal infection (RR, 0.80; CI, 0.39-1.67). The beneficial effect of
      antifungal prophylaxis was predominantly associated with the reduction of Candida
      albicans infection and mortality attributable to C. albicans. Compared to
      controls, however, patients receiving prophylaxis experienced a higher proportion
      of episodes of non-albicans Candida, and in particular of C. glabrata. No
      beneficial effect on invasive Aspergillus infection was observed. In conclusion,
      our analysis shows a clear, though limited, beneficial effect of antifungal
      prophylaxis in liver transplant patients. Concerns about the selection of
      triazole-resistant Candida strains, however, are realistic, and the potential
      disadvantages of prophylaxis should be weighed against the established benefits.

PMID- 16628698
TI  - Immune thrombocytopenic purpura following liver transplantation: a case series
      and review of the literature.
AB  - Thrombocytopenia is common among liver transplant candidates and recipients. The
      aim of our study was to determine the incidence and outcome of new-onset immune
      mediated thrombocytopenic purpura (ITP) following liver transplantation at a
      single center. Among the 256 liver transplant recipients with an International
      Classification of Diseases, Ninth Edition code for thrombocytopenia, 8 cases of
      new-onset ITP were identified, leading to an overall incidence of 0.7% in 1,105
      consecutive liver transplant recipients over a 15-year period. All 8 patients
      were Caucasian, 5 (63%) were male, and the median age at ITP onset was 54 years
      (range, 15-63). The median platelet count at presentation was 3,500 cells/mL
      (range, 1,000-12,000) and liver disease was due to hepatitis C (38%), primary
      sclerosing cholangitis (38%), and cryptogenic cirrhosis (25%). The median time
      from transplant to ITP onset was 53.5 months (range, 1.9-173). Three of the 6
      patients tested (50%) had cell-bound antiplatelet antibodies, 1 patient had an
      underlying hematological malignancy, and none of the organ donors had a history
      of ITP. Corticosteroids and/or immunoglobulin infusions were effective in 4
      patients. However, serial rituximab infusions were required in 4 patients with
      persistent thrombocytopenia, and 3 of them eventually required splenectomy to
      induce disease remission. At a median follow-up of 19.7 months, 7 long-term
      survivors remain in remission with a median platelet count of 267,000 cells/mL.
      In conclusion, new-onset ITP is an infrequent but important cause of severe
      thrombocytopenia in liver transplant recipients. Corticosteroids and
      immunoglobulin infusions were effective in 50% while the remainder of patients
      required rituximab infusions or eventual splenectomy for long-term disease
      remission.

PMID- 16628699
TI  - Pegylated interferon-induced immune-mediated hepatitis post-liver
      transplantation.
AB  - A 55-year-old Caucasian male developed a well characterized autoimmune hepatitis
      after completing treatment with pegylated interferon and ribavirin for recurrent
      hepatitis C. We hypothesize that pegylated interferon triggered a severe form of
      immune-mediated hepatitis.

PMID- 16628700
TI  - Probabilities of relapse and abstinence among liver transplant recipients.

PMID- 16628701
TI  - Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5
      gene polymorphisms in Chinese liver transplant patients.
AB  - The aim of this study was to investigate whether the heterogeneity in tacrolimus
      dose requirement is associated with ABCB1 and CYP3A5 gene polymorphisms in
      Chinese liver transplant patients during the first month after transplantation.
      ABCB1 and CYP3A5 genotyping was performed using the polymerase chain reaction
      restriction sites polymorphism-based procedure in Chinese liver transplant
      recipients (n = 50) and their corresponding donors (n = 50). Tacrolimus whole
      blood trough concentrations were measured by immunoassays on the IMx analyzers
      (Abbott Diagnostics Laboratories, Abbott-Park, IL). Doses required to achieve
      target blood concentrations and dose-adjusted trough concentrations
      (concentration/dose [C/D] ratios) were compared among patients according to
      allelic status of ABCB1 and CYP3A5. The ABCB1 3435CC was observed in 23 subjects
      (23%), whereas 64 (64%) carried 3435CT and 13 (13%) carried 3435TT. The
      CYP3A5*1/*1 was observed in 13 subjects (13%), 50 (50%) carried *1/*3, and 37
      (37%) carried*3/*3. The tacrolimus C/D ratios were obviously lower in recipients
      carrying ABCB1 3435CC genotype. For CYP3A5, recipients who received organs from
      CYP3A5*3/*3 donors had higher C/D ratios. But the donors' ABCB1 and recipients'
      CYP3A5 genotype did not affect the recipients' pharmacokinetics. Analysis of the
      combination of recipients' ABCB1 and donors' CYP3A5 genotypes revealed that the
      tacrolimus C/D ratios were significantly lower in the ABCB1 3435CC-carrying
      recipients, regardless of donors' CYP3A5 genotype. In conclusion, our finding
      suggests that the recipients' ABCB1 and donors' CYP3A5 genotype affect the
      tacrolimus dose requirements. ABCB1 C3435T polymorphism is a major determinant of
      tacrolimus trough concentration in Chinese liver transplant recipients, and
      recipients with 3435CC genotype will require higher dose of tacrolimus.

PMID- 16628703
TI  - Selective coil occlusion of a large arterioportal fistula in a liver graft.

PMID- 16628704
TI  - The difficulty in timing for liver transplantation in cirrhotic patients
      coinfected with HIV: in search for a prognosis score.

PMID- 16628705
TI  - Antioxidant therapy in liver ischemia-reperfusion injury.

PMID- 16628706
TI  - Radiofrequency ablation for hepatocellular carcinoma in so-called high-risk
      locations.
AB  - We evaluated the efficacy and safety of radiofrequency (RF) ablation for
      hepatocellular carcinoma (HCC) in presumably high-risk locations. Between
      February 1999 and December 2001, we performed RF ablation on 1419 nodules in 636
      consecutive HCC patients, of which 231 nodules in 207 patients were in high-risk
      locations, defined as less than 5 mm from a large vessel or an extrahepatic
      organ. Eighty-one patients had a nodule adjacent to a large vessel, 145 patients
      had a nodule adjacent to an extrahepatic organ, of whom 19 also had one adjacent
      to a large vessel. Early complications and local tumor progression were analyzed
      with regard to the location of each nodule. The mean nodule diameter and average
      number per patient were 27 mm and 2.3, respectively. Early complications, within
      30 days after ablation, occurred in 12 of 207 patients (5.8%) with a nodule in a
      high-risk location and in 15 of 429 patients (3.5%) without (P = .1776). There
      was no significant difference in local tumor progression rate between nodules in
      high-risk locations (1 year: 2.1%, 2 years: 3.1%, 3 years: 3.1%) and those
      elsewhere (1 year: 0.6%, 2 years: 1.7%, 3 years: 2.5%) (P = .2745). In
      conclusion, HCC nodules adjacent to a large vessel or extrahepatic organ were
      treated with RF ablation without compromising the efficacy of the procedure.
      However, even though without significant difference, some complications occurred
      at risky locations and need to be carefully considered.

PMID- 16628707
TI  - Self-assembling peptides as injectable lubricants for osteoarthritis.
AB  - The self-assembly of peptides is explored as an alternative route towards the
      development of new injectable joint lubricants for osteoarthritis (OA). The
      versatility of the peptide chemistry allows the incorporation of behavior
      reminiscent of hyaluronic acid (HA), while the triggered in situ self-assembly
      provides easy delivery of the samples by injection due to the low viscosity of
      the peptide solutions (that are initially monomeric). Using design criteria based
      on the chemical properties of HA, a range of de novo peptides were prepared with
      systematic alterations of charge and hydrophilicity that self-assembled into
      nematic fluids and gels in physiological solution conditions. The frictional
      characteristics of the peptides were evaluated using cartilage on cartilage
      sliding contacts along with their rheological characteristics. Peptide P(11)-9,
      whose molecular, mesoscopic, and rheological properties most closely resembled HA
      was found to be the most effective lubricant amongst the peptides. In healthy
      static and dynamic friction testing (corresponding to healthy joints) P(11)-9 at
      20-40 mg/mL performed similar to HA at 10 mg/mL. In friction tests with damaged
      cartilage (corresponding to early stage OA) P(11)-9 was a less efficient
      lubricant than HA, but still the best among all the peptides tested. The results
      indicate that de novo self-assembling peptides could be developed as an alternate
      therapeutic lubricant for early stage OA.

PMID- 16628708
TI  - In vitro and in vivo (cyto)toxicity assays using PVC and LDPE as model materials.
AB  - The choice for a biomaterial is partly based on the outcome of (cyto)toxicity
      assays. The rationales behind the selection of certain parameters, such as cell
      lines, controls, and animals, were evaluated using a positive and a negative
      control, and one experimental sample designed to induce intermediate toxicity.
      Extraction and direct contact assays were performed using human epidermal
      keratinocytes and mouse fibroblasts and mouse epithelial cells. Cell survival was
      measured with the tetrazolium salt (MTT) reduction assay. In addition, local
      implantation studies were performed in mice and rats. The positive control
      induced a high degree of toxicity in all in vitro tests performed, indicating
      that the toxicity observed in the direct contact assay was due to in situ
      extraction of toxic components. In the direct contact assay the negative control
      tested on the mouse fibroblasts resulted in a significant reduction of cell
      survival. No decrease in cell survival was found using the experimental sample.
      Subcutaneous implantation studies in mice showed that the positive control
      material induced a severe degeneration in mice. However, in rats just minimal
      alterations were noted. The experimental material induced moderate responses only
      in mice. Our results indicate that the direct contact assay provides limited
      additional information on the cytotoxicity of materials if certain limitations
      are not taken into account. For the in vivo implantation assay mice were superior
      to rats in detecting local toxic responses.

PMID- 16628709
TI  - Influence of hydroxyapatite microstructure on human bone cell response.
AB  - Microstructure of calcium phosphate ceramics has been shown to influence long
      term in vitro cellular events like proliferation and differentiation, and to
      favor bone integration in vivo. As long-term cellular events are known to be
      dependent of early cell adhesion events, we decided to study the in vitro
      influence of the microstructure of a microporous hydroxyapatite (mHA) and a
      nonmicroporous hydroxyapatite (pHA) ceramic on serum protein adsorption and SaOs
      2 human bone cells attachment after 30 min, 1, 4, and 24 h and cell growth after
      96 h. Plastic coverslips were used as controls. Hydroxyapatite composition of mHA
      and pHA was confirmed by X-ray diffraction and Fourier transform infra-red
      spectroscopy. The surface energies of ceramics were calculated from contact-angle
      measurements in di-iodomethane, water or complete culture medium. The total
      surface energy was 44.8 mJ/m(2) for pHA and 48.7 mJ/m(2) for plastic. The contact
      angle measurement was impossible on mHA likely because they displayed 12% of open
      microporosity, pHA ceramic exhibiting only closed pores (2.5%). Moreover, the
      roughness amplitude was largely higher on mHA (Sa = 4.35 microm) than on pHA (Sa
      = 0.065 microm) and plastic (Sa = 0.042 microm). Three different techniques were
      used to evaluate protein adsorption on the ceramics. SDS-PAGE of desorbed
      proteins demonstrated that more proteins desorbed from mHA (66.02 microg/m(2))
      than from pHA (17.2 microg/m(2)) or plastic (0.08 microg/m(2)). A new method was
      used to evaluate in situ the quantity of adsorbed total proteins: the temperature
      programmed desorption (TPD) analysis coupled with mass spectrometry. The TPD
      analysis confirmed that 10-fold more proteins adsorbed on mHA compared with those
      on pHA. A direct immunolabeling on ceramics revealed than more fibronectin and
      serum albumin adsorbed on microporous ceramic than on dense ceramic. The
      morphology of SaOs-2 cells was the same on all the substrates after 30 min. At
      later time points, cell morphology on mHA was radically different than on other
      surfaces, with the particularity of the cytoplasmic edge that appeared
      undistinguishable from the surface. Only the extremity of the cells and
      lamellipodia were visible. Cells seemed like "adsorbed" by the mHA surface,
      whereas on plastic and pHA surfaces the cells displayed classical aspects of
      polygonal spreading. The cells displayed on mHA the highest initial attachment
      potential after 30 min, 1, 4, 24 h but the lower proliferation potential after
      four days. This study confirms that a microporous ceramic surface can modulate
      the adsorption of proteins and further the adhesion and proliferation of human
      bone cells.

PMID- 16628710
TI  - Hydrophilic nanofibrous structure of polylactide; fabrication and cell affinity.
AB  - Microstructure and architecture of the scaffolds along with the surface chemistry
      exert profound effect on biological activity (cell distribution, proliferation,
      and differentiation). For the biological activity, scaffolds in tissue
      engineering have been widely designed. The objective of this study was to develop
      hydrophilic nanofibrous structure of polylactides (PLLA) polymer in the form of
      nonwoven mat by electrospinning technique, and further evaluate the fibroblast
      NIH3T3 cell proliferation, morphology, and cell-matrix interaction.
      Hydrophilicity of the PLLA fibers was improved by adding small fraction of low
      molecular weight polyethylene glycol (PEG) into the electrospinning solution.
      Four different ratio types (100/0, 80/20, 70/30, and 50/50) of PLLA/PEG
      electrospun matrices were fabricated, and the pore characteristics, tensile
      properties, contact angle, and hydrolytic degradation were observed. Furthermore,
      scanning electron microscope (SEM) and fluorescence actin staining images were
      used for micro-observation of cell-matrix interaction and cell morphology. It was
      found that the electrospun mat of PLLA/PEG (80/20), composed of fibers with
      diameters in the range 540-850 nm, majority of pore diameter less than 100
      microm, tensile strength 8 MPa, elongation 150%, porosity more than 90%, and
      improved hydrophilicity with slow hydrolytic degradation, is favorable for
      biological activity of NIH3T3 fibroblast cell. Based on these results, the
      correct composition of PLLA and PEG in the porous electrospun matrix (i.e.,
      PLLA/PEG (80/20)) will be a better candidate rather than other compositions of
      PLLA/PEG as well as hydrophobic PLLA for application in tissue engineering.

PMID- 16628711
TI  - The influence of the crystallinity of electrostatic spray deposition-derived
      coatings on osteoblast-like cell behavior, in vitro.
AB  - This article describes the influence of the crystallinity of carbonate apatite
      (CA) coatings on osteoblast-like cell behavior. Porous CA coatings were produced
      with electrostatic spray deposition (ESD), and subsequently, received heat
      treatments of 400, 500, or 700 degrees C to induce various coating
      crystallinities. As a result, an amorphous calcium phosphate (ACP), a crystalline
      CA (CCA), and a crystalline carbonated hydroxyapatite (CHA) structure were
      formed, respectively. Uncoated titanium substrates served as the control group.
      After seeding rat osteoblast-like cells, the initial cell attachment was similar
      between the groups, and approached 100% after 6 h. Between the various coatings,
      no differences were observed for proliferation, differentiation, or
      mineralization. However, proliferation of the osteoblast-like cells was lower on
      all coated substrates after longer culture periods, compared to the uncoated
      substrates, while at the same time differentiation was stimulated. Furthermore,
      after 8 and 16 days of incubation, scanning electron microscopy showed more signs
      of mineralization on coated substrates, compared to the uncoated substrates. In
      conclusion, porous ESD-derived CA coatings have a positive effect on the in vitro
      differentiation of osteoblast-like cells, compared to uncoated, as-machined
      titanium. However, this effect is not further enhanced by the degree of
      crystallinity of the ESD-derived CA coatings.

PMID- 16628712
TI  - Site-specific delivery of dexamethasone from biodegradable implants reduces
      formation of pericardial adhesions in rabbits.
AB  - Repeated sternotomy often leads to serious complications in patients due to the
      formation of cardiac adhesions. In this study we characterized dexamethasone
      loaded biodegradable poly(lactide)-poly(ethyleneglycol) copolymer films for site
      specific drug delivery and examined their efficacy in the rabbit model of
      postoperative cardiac adhesions. Tritiated dexamethasone-loaded films were used
      to determine the in vitro release and in vivo drug distribution. Dexamethasone
      release in serum was biphasic with 69% drug released after 72 hr. The implants
      produced sustained drug levels at the implantation site with low distribution
      into the peripheral tissues. The matrices were implanted in rabbits between the
      epicardium and the sternum following sternotomy, pericardiectomy and epicardium
      abrasion, with the drug-releasing surface facing the epicardium. The tenacity and
      density of the adhesions was examined 21 days post procedure in comparison to
      both groups of untreated and rabbits implanted with blank matrices. Similarly
      tenacious and dense adhesions were observed in both control groups. In contrast,
      epicardial adhesions' formation was significantly reduced and the anatomy was
      preserved in the treated animals. It is concluded that local delivery of
      dexamethasone from biodegradable implants provides a promising approach for the
      prevention of pericardial adhesions while potentially minimizing the systemic
      adverse effects inherent to systemic therapy or high blood levels of the drug.

PMID- 16628714
TI  - Actin polymerization in neutrophils from donors of peripheral blood stem cells:
      divergent effects of glycosylated and nonglycosylated recombinant human
      granulocyte colony-stimulating factor.
AB  - Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF)
      treatment, with divergent effects on phagocytosis, motility, bactericidal
      activity, and surface molecule expression. Neutrophil morphology is modified by
      treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not
      affected by lenograstim (the glycosylated type of rhG-CSF). Little information is
      available about actin polymerization in neutrophils from subjects treated with
      the two types of rhG-CSF. In the current paper we evaluated two groups of donors
      of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten
      subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC;
      15 blood donors were evaluated as a control group. Actin polymerization (both
      spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A
      microscopic fluorescent assay was also carried out to evaluate F-actin
      distribution in neutrophils. We found that filgrastim induced an increased F
      actin content in resting neutrophils, along with morphologic evidence for
      increased actin polymerization distributed principally at the cell membrane and
      frequently polarized in focal areas; in addition, fMLP was not able to induce
      further actin polymerization. On the contrary, treatment with lenograstim was
      associated with F-actin content, distribution, and polymerization kinetics
      indistinguishable from those displayed by control neutrophils. Such experimental
      results show that filgrastim and lenograstim display divergent effects also on
      neutrophil actin polymerization and provide further explanation for previous
      experimental findings.

PMID- 16628715
TI  - Bisphosphonates may potentiate effects of thalidomide-dexamethasone combination
      in advanced multiple myeloma.

PMID- 16628716
TI  - Prognostic significance of Fas (CD95/APO-1) positivity in patients with primary
      nodal diffuse large B-cell lymphoma.
AB  - Fas (CD95/APO-1) is a protein that is mainly related to apoptosis of lymphoid
      cells. The increment of Fas expression is associated with long-term survival in
      various malignancies. However, there are limited studies regarding the effect of
      Fas expression on the course and prognosis of non-Hodgkin's lymphoma. The aim of
      this study was to investigate the significance of immunohistochemical Fas
      expression on the prognosis of nodal diffuse large B-cell lymphoma. A total of 63
      patients with primary nodal diffuse large B-cell lymphoma diagnosed in the
      Erciyes University Department of Hematology between 1990 and 2003 were included
      in the study. The median age of the patients was 55 years old (range 19-102 years
      old). The median follow-up period was 19 months (2-132 months). Histopathological
      sections were stained immunohistochemically and evaluated by light microscopy for
      Fas, bcl-2, and p53. Clinical and laboratory parameters including Fas, bcl-2, and
      p53 positivity, age, sex, performance status, clinical stage, presence of B
      symptoms, bone marrow involvement, extranodal involvement, and lactic
      dehydrogenase levels were evaluated to compare overall survival. Complete
      remission was obtained in 28 patients (44.4%) after first-line chemotherapy. Fas
      positivity, male gender, good performance status, clinical stage I-II, absence of
      B symptoms, normal lactic dehydrogenase value, and absence of bone marrow
      involvement were favorable prognostic factors for complete remission in
      statistical analysis. Multivariate analysis revealed that positive Fas expression
      and ECOG performance status were independent prognostic factors for overall
      survival. Also, Fas-positive patients had significantly prolonged progression
      free survival. Immunohistochemical Fas positivity was a favorable prognostic
      factor for complete remission and overall and progression-free survival in
      primary nodal diffuse large B-cell lymphoma.

PMID- 16628717
TI  - Epstein-Barr virus reactivation in a patient treated with anti-thymocyte globulin
      for severe aplastic anemia.
AB  - Epstein-Barr virus (EBV) infection and reactivation is an increasing complication
      in immune deficient patients, particularly after allogeneic hematopoietic stem
      cell transplantation (HSCT). Therapy with anti-thymocyte globulin (ATG) is
      associated with higher incidence of EBV-related disease in HSCT patients, but
      this risk is not documented in patients receiving ATG for severe aplastic anemia
      (SAA). We describe the case of a patient who developed an EBV infection, with the
      clinical features of an infectious mononucleosis, after immune suppression with
      cyclosporine and two courses of ATG for SAA.

PMID- 16628718
TI  - Severe bone marrow necrosis without suggestive features.

PMID- 16628719
TI  - Reduced intensity conditioning allogeneic bone marrow transplantation following
      central nervous system (CNS) relapse of acute promyelocytic leukemia: evidence
      for a graft-versus-leukemia effect in the CNS.

PMID- 16628721
TI  - Cerebral vaso-occlusive event with low-osmolar intravenous contrast in a patient
      with sickle cell disease.

PMID- 16628722
TI  - An unusual case of Bardet-Biedl syndrome presenting with pancytopenia.

PMID- 16628723
TI  - A prospective study of the prevalence of heparin-induced antibodies and other
      associated thromboembolic risk factors in pediatric patients undergoing
      hemodialysis.
AB  - Heparin, which is used at high doses in hemodialysis patients, may induce
      antibodies favoring thromboembolic complications. We prospectively investigated
      the prevalence of heparin-induced platelet-reactive antibodies in a cohort of 38
      pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4)
      ELISA and heparin-induced platelet activation assay (HIPA). We also assessed
      other acquired and congenital hypercoagulable states. Heparin-induced antibodies
      were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti
      H/PF4 antibodies were negatively correlated with the number of hemodialysis
      sessions. These antibodies disappeared after a median time of 6 months despite
      continuing heparin treatment. The prevalence of antiphospholipid antibodies was
      21% (anticardiolipin 10.5%, anti-beta2GPI 13%, and lupus anticoagulant 5%). Blood
      levels of homocysteine, factor VIII, and fibrinogen were significantly higher and
      factor II levels were significantly lower in hemodialysis patients than in
      controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels
      were similar in patients and controls. Overall, 26 of 38 patients had at least
      one biomarker of hypercoagulability, but only 1 patient, without anti-H/PF4
      antibodies, presented with thrombosis. In conclusion, heparin induces the
      transient production of anti-H/PF4 antibodies in children undergoing
      hemodialysis, but other abnormalities probably contribute to hypercoagulability.
      These findings may help to improve the diagnosis and management of thrombotic
      events in hemodialysis patients.

PMID- 16628724
TI  - Hemoglobinopathies mimicking Hb S/beta-thalassemia: Hb S/S with alpha-thalassemia
      and Hb S/Volga.
AB  - There are approximately 1200 known natural mutations of the human globin genes.
      In most clinical laboratories, the diagnosis of hemoglobin disorders is based on
      blood counts, hemoglobin electrophoresis, or column chromatography, which can
      identify common variant hemoglobins such as Hb S, C, and E, but are unable to
      definitively diagnose most other hemoglobin variants and thalassemia mutations.
      We report two unrelated cases, both thought initially to have Hb S/beta
      thalassemia. Subsequent mutational analyses revealed that one is Hb S/S with
      compound heterozygosity for nondeletional alpha-thalassemia mutations. The other
      is the first reported case of compound heterozygosity for Hb S and an unstable
      hemoglobin, Hb Volga. Correct diagnoses of these hereditary disorders are needed
      for prognosis and proper management and also for genetic counseling. These
      studies underscore the importance to correlate clinical course with laboratory
      diagnosis and to make DNA-based diagnostics more widely available for patients
      with unusual or complicated hemoglobin disorders.

PMID- 16628725
TI  - Torsades de pointes upon fluconazole administration in a patient with acute
      myeloblastic leukemia.
AB  - Prolonged QT syndrome often causes torsades de pointes (Tdp), a potentially
      lethal arrhythmia. A 55-year-old woman with M4Eo who was receiving consolidation
      chemotherapy had an episode of prolonged QT and Tdp following fluconazole (FCZ)
      administration. Intravenous supplementation of magnesium sulfate and multiple
      attempts at electrocardioversion led to recovery from the arrhythmia. FCZ appears
      to contribute to the development of QT prolongation, in particular with low
      concentrations of serum potassium or magnesium. Although mechanisms of Tdp
      development in patients with QT prolongation remain to be determined, it is
      possible that FCZ administration leads to manifestation of Tdp. Special cautions
      should be exercised upon the emergence of QT prolongation following FCZ
      administration.

PMID- 16628726
TI  - Novel valproic acid derivatives with hemoglobin F inducing activity.
AB  - Pharmacological induction of hemoglobin F expression may be a promising approach
      for the treatment of beta-thalassemia and sickle cell disease. Valproic acid, a
      drug frequently used for the treatment of seizure disorders, has been shown to
      enhance fetal hemoglobin synthesis in erythroid cells. However, this effect is
      only modest and requires relative high concentrations. Therefore, the drug
      appears not to be applicable for the treatment of beta-globin chain disorders.
      Here, we describe the identification of novel valproic acid derivatives with
      potent hemoglobin F inducing activities at concentrations that presumably can be
      obtained in vivo.

PMID- 16628727
TI  - Unusual severe development of common B lymphoblastic leukemia in Gaucher disease
      type I.

PMID- 16628728
TI  - Gastrointestinal endoscopic findings in men with unexplained anemia and low
      normal ferritin values.
AB  - BACKGROUND: Most practice guidelines recommend endoscopic evaluation of the
      gastrointestinal (GI) tract in men and postmenopausal women with anemia and a
      serum ferritin less than 20-40 ng/ml. The diagnostic yield of endoscopy in
      patients with anemia, no GI symptoms or signs, and low normal ferritin is not
      known. OBJECTIVE: The aim of this study was to investigate the yield of upper and
      lower GI endoscopic evaluations in anemic patients with ferritin levels between
      40 and 100 ng/ml. DESIGN: A retrospective review of patients' charts was
      conducted. SUBJECTS AND METHODS: Patients at the Veterans Affairs Connecticut
      Healthcare System who underwent GI endoscopic evaluation for the sole indication
      of anemia and ferritin in the low normal range (40-100 ng/ml) were included in
      this study. MEASUREMENTS: Incidence of pathology of the upper and lower GI tract
      was determined. RESULTS: We identified 54 male patients who had a ferritin level
      of 40-100 ng/ml and no GI symptoms or known GI bleeding. Upper GI findings
      (malignancy, peptic ulcers, Helicobacter pylori gastritis, arteriovenous
      malformations) were found in 14/47 cases (30%). Lower gastrointestinal findings,
      including large tubular adenomas and arteriovenous malformation, were identified
      in 3/53 cases (6.7%). CONCLUSION: Our study supports GI endoscopy in anemic
      patients with ferritin between 40 and 100 ng/ml, even in the absence of GI
      symptoms or documented bleeding.

PMID- 16628729
TI  - Allele frequencies of three factor VIII gene polymorphisms in Iranian populations
      and their application in hemophilia A carrier detection.
AB  - Hemophilia A is an X-linked recessive bleeding disorder caused by a quantitative
      or qualitative deficiency of blood coagulation factor VIII (FVIII). ARMS
      (amplification refractory mutation system) primers were designed to determine
      allele frequencies of three FVIII gene linked markers, IVS7 nt 27 G/A SNP,
      BclI/intron 18, and HindIII/intron 19 among 85 normal Iranian women from
      unrelated families. Then same method was applied to perform carrier detection for
      hemophilia A families. The allele frequencies of IVS7 nt 27 "G"/"A" allele, BclI
      "T"/"A" allele, and HindIII "C"/"T" allele among normal women were 0.88/0.12,
      0.52/0.48, and 0.48/0.52, respectively. The three polymorphisms were found to be
      in strong linkage disequilibrium, which decreased the overall heterozygosity to
      51%. Twenty-one women from 15 unrelated hemophilia A families were referred to us
      for hemophilia A carrier detection. Taking advantage of these three biallelic
      polymorphisms in conjunction with multiallelic St14 VNTR (locus DXS52), IVS13
      (CA)n STR, and IVS22 (CA)n STR, carrier status was determined in 16 women (16/21
      or 76% of the at-risk women) from 11 families (11/15 or 73% of the families). The
      used ARMS methods are rapid and can easily be applied in conjunction with other
      FVIII gene linked polymorphisms for indirect mutation detection of hemophilia A
      where they are informative.

PMID- 16628730
TI  - Analysis of serum granulysin in patients with hematopoietic stem-cell
      transplantation: its usefulness as a marker of graft-versus-host reaction.
AB  - Granulysin is a newly identified CTL/NK cell-related cytotoxic protein, which is
      secreted in both constitutive and Ca-dependent manner. To evaluate its
      significance in stem-cell transplantation (SCT), serum granulysin was measured by
      newly established ELISA method in 26 patients undergoing SCT (21 allogeneic and 5
      autologous). In the allogeneic SCT, granulysin was transiently increased in 3
      weeks, which was not observed in autologous SCT. In acute GVHD, serum granulysin
      was markedly increased and correlated with the severity of GVHD. Elevation of
      granulysin was not necessarily associated with increase of sIL2R or IFN-gamma. In
      vitro, allospecific T cells released granulysin in an allo-specific manner, and
      it was correlated with allo-specific cytotoxic activity. These results indicate
      that increased release of granulysin presents alloreactivity and serum granulysin
      is useful as a marker of GVHD in SCT.

PMID- 16628731
TI  - Clustered incidence of acute promyelocytic leukemia during gefitinib treatment
      for non-small-cell lung cancer: experience at a single institution.
AB  - Although gefitinib, an epidermal growth factor receptor tyrosine kinase
      inhibitor, has been shown a significant activity for recurrent non-small-cell
      lung cancer (NSCLC), its long-term adverse effect with its continuous usage has
      hitherto not been clearly elucidated. Subjects were 108 consecutive NSCLC cases
      who were treated with gefitinib between November 2001 and December 2004 at our
      single institution. A crude incidence rate ratio was calculated by ratio of crude
      incidence rate in our subject to population-based incident rate of all leukemia
      (ICD: C91-95) in the same region. The 95% confidence intervals (CIs) were
      calculated based upon a Poisson distribution. Three cases of acute promyelocytic
      leukemia (APL) occurred during gefitinib treatment, and these patients' past
      treatment histories are presented herein. No other malignancy was identified. All
      of the cases were diagnosed at the stage of mild-to-moderate cytopenia,
      especially thrombocytopenia, without disseminated intravascular coagulation. All
      presented a normal karyotype with positive PML-RARalpha in RT-PCR, indicating
      submicroscopic translocation. They responded well to APL treatments, including
      all-trans-retinoic acid. The crude incident rate ratio was 639.9 (95% confidence
      interval: 131.6-1,878.9, P < 0.0001) when the APL incidence in this cohort was
      compared to all leukemia cases in the general population in the same district in
      Japan. Thus we had three cases of secondary APL patients within the gefitinib
      treated NSCLC cohort. Although we cannot exclude an effect of past exposure of
      other cytotoxic agents and radiotherapy as a cause of APL, APL inducibility of
      gefitinib should be clarified in the further study.

PMID- 16628732
TI  - Hb Florida: a novel elongated C-terminal beta-globin variant causing dominant
      beta-thalassemia phenotype.
AB  - We report here a new frameshift mutation in exon 3 of the beta-globin gene, a
      single nucleotide deletion (-C) in between codons 140/141 (GCC/CTG-->GCC/TG),
      found in an 8-year-old Argentinean girl with clinical picture of thalassemia
      intermedia. It leads to a beta-chain that is elongated to 156 amino acids
      [(141)Trp-Pro-Thr-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser-Asn-Phe-(156)Tyr-COOH].
      The resulting hemoglobin, which we named Hb Florida, was not detected in
      peripheral blood; however, erythroid hyperplasia and dyserythropoiesis with large
      inclusion bodies on methyl violet staining were observed in bone marrow,
      suggesting that this is a hyperunstable variant producing a dominant beta
      thalassemia phenotype, since the other beta-allele was completely normal.

PMID- 16628733
TI  - Arteriosclerotic events are less frequent in persons with chronic anemia:
      evidence from families with hereditary spherocytosis.
AB  - Because anemic persons have lower cholesterol and whole blood viscosity than
      those who are not anemic, we hypothesized that subjects with hereditary
      spherocytosis who have not had the spleen removed should have fewer
      arteriosclerotic events than unaffected family members. We defined
      arteriosclerotic events as myocardial infarct, stroke, coronary artery surgery,
      and carotid artery surgery. We compared the rate of these events in affected-not
      splenectomized persons to the rate in unaffected family members. The relative
      risk of an arteriosclerotic event in hereditary spherocytosis patients with a
      spleen was one fifth that in unaffected family members. These data support the
      hypothesis that chronic anemia retards the development of arteriosclerosis.
      Spherocytosis is another example of an inherited condition that conveys an
      advantage in one system and a disadvantage in another.

PMID- 16628734
TI  - Donor cell leukemia in a patient developing 11 months after an allogeneic bone
      marrow transplantation for chronic myeloid leukemia.
AB  - A 38-year-old female with chronic myeloid leukemia underwent an allogeneic bone
      marrow transplantation from her full-matched brother. Eleven months later, she
      readmitted with an acute leukemia that was shown to be of donor origin. The
      patient never achieved a remission even after chemotherapies with cytarabine and
      mitoxantrone, donor lymphocyte infusion, and second allogeneic peripheral blood
      stem cell transplantation. Donor cell leukemia (DCL) is sometimes misdiagnosed as
      relapse by clinicians and the real incidence may be higher than expected.
      Cytogenetic and molecular techniques may be helpful to clarify the issue of the
      leukemia. The current case is another case of DCL reported in the literature
      after an allogeneic transplant for a kind of leukemia.

PMID- 16628735
TI  - UGT1A1 polymorphism outweighs the modest effect of deletional (-3.7 kb) alpha
      thalassemia on cholelithogenesis in sickle cell anemia.
AB  - Enhanced erythrocyte destruction in sickle cell anemia results in chronic
      hyperbilirubinemia. Only a subset of patients develop cholelithiasis. UGT1A1
      promoter polymorphism is associated both with unconjugated bilirubin level and
      elevated risk for cholelithiasis in such subset. Here, we investigated the role
      of alpha-thalassemia, yet another genetic factor that modulates hemolysis, in
      conferring protection from cholelithiasis. We show that, although alpha
      thalassemia is associated with modest reduction in hemolysis and unconjugated
      bilirubin level, UGT1A1 polymorphism outweighs its effect on cholethiogenesis in
      sickle cell anemia patients.

PMID- 16628736
TI  - Chronic myeloid leukemia in accelerated phase with basophilic transformation of
      the bone marrow.

PMID- 16628737
TI  - Cryptococcus neoformans meningitis in a patient with hairy cell leukemia.

PMID- 16628738
TI  - Cardiovascular involvement in adult granulocytic sarcoma.

PMID- 16628739
TI  - Investigation of the absorption mechanisms of baicalin and baicalein in rats.
AB  - To characterize and compare the absorption mechanisms of baicalin (BG) and
      baicalein (B), either of them was perfused in situ in rats with ligation of the
      bile duct as well as without it. Two RP-HPLC methods were developed to determine
      the drugs' concentrations in the gastric and intestinal perfusates, respectively.
      The result showed that BG was moderately absorbed in stomach but poorly in small
      intestine and colon, while B was well absorbed in stomach and small intestine but
      relatively less in colon. It also indicated that bile could excrete BG and
      significantly promote the absorption of B. When BG or B was perfused alone in the
      small intestine after ligation of the bile duct, there came out to be increasing
      B or BG in the perfusate, respectively. In addition, when B was intravenously
      administered to rats after ligation of the bile duct, there came out to be BG in
      the intestinal perfusate. In conclusion, B was more suitable to be administered
      orally than BG, which was absorbed as B and then restored to BG in the body. Part
      of the BG formed from the absorbed or intravenously administered B could be
      excreted back into the gut.

PMID- 16628740
TI  - Phrenic nerve neurotization of the musculocutaneous nerve with end-to-side
      neurorrhaphy: a short report in a rabbit model.
AB  - This experimental study was performed to evaluate the efficacy of end-to-side
      coaptation between the musculocutaneous nerve and the phrenic nerve for brachial
      plexus injuries with nerve-root avulsions. In an experimental rabbit model,
      neurotization of the musculocutaneous nerve with the phrenic nerve was compared
      using end-to-end and end-to-side neurorrhaphy. Preliminary results from
      electrophysiologic and histologic examinations indicate that end-to-side
      neurotization of the musculocutaneous nerve with the phrenic nerve is an
      effective means for musculocutaneous nerve repair. The effectiveness of the
      phrenic nerve is attributed to its large number of motor axons.

PMID- 16628741
TI  - Sciatic and peroneal nerve injuries.
AB  - In the past, the attitude toward surgical repair of sciatic and peroneal nerve
      lesions was excessively pessimistic. Refinements of microsurgical technique,
      nerve conduction studies, and the establishment of indications and optimal
      timings for surgical interventions have led to significant improvements in
      outcomes, making repair worthwhile in most cases. Tendon transfers can augment
      functional outcomes, and are performed as secondary procedures or (in selected
      cases) in combination with the initial repair. Developments in the basic
      sciences, bioengineering, and medical imaging may further improve the results of
      management of these serious nerve injuries.

PMID- 16628742
TI  - Facial paralysis.
AB  - Detailed knowledge of embryology, anatomy, and function of the facial nerve is
      essential in treating the devastating functional, aesthetic, and psychological
      sequelae of facial paralysis. Two basic factors influence the method of repair
      and the subsequent outcome of the effort to combat facial paralysis. First is the
      availability of a viable proximal nerve stump which can be used as the source for
      motor axons, and which is related to the level of the injury. Second is the
      duration of the paralysis, which will dictate the possibility of reinnervating
      the facial muscles. Early restoration of nerve continuity, and therefore
      reestablishment of the neuromuscular junction and preservation of the function of
      the facial muscles, lead to superior functional and aesthetic rehabilitation.
      Secondary reconstruction, after the establishment of atrophy of the motor
      endplates of the facial muscles, is possible with nerve grafts and microsurgical
      free functional muscle transfer. These techniques, although not perfect, greatly
      improve aesthetic balance and alleviate the functional and psychological
      implications of the paralysis.

PMID- 16628743
TI  - Primary nerve repair in associated lesions of the axillary artery and brachial
      plexus.
AB  - Diagnosis becomes more complex when there is an association of a brachial plexus
      injury with an arterial lesion. The principal clinical picture in most cases is
      acute ischemia that requires initial treatment in the emergency room, and the
      final results of nerve repair are generally poorer. Although delayed brachial
      plexus reconstruction is preferred by some authors, our experience leads us to
      the opinion that a combined repair presents several advantages. Immediately after
      trauma, the surgical field is free of scar tissue, and a precise evaluation of
      both the number and level of damaged nerves may be made. Vascular and nerve
      repair may be mutually agreed upon by both the vascular surgeon and microsurgeon,
      and simple sutures may often be used instead of grafts in early nerve repair.
      Even if the extent of nerve damage may sometimes be difficult to assess, the
      results of early, easier repairs can be observed in our series of 14 combined
      lesions. Our results indicate that collaboration between microsurgeons and
      vascular surgeons is a very important factor in providing a correct approach to
      these problematic patients.

PMID- 16628745
TI  - Long-term evaluation of rabbit peripheral nerve repair with end-to-side
      neurorrhaphy in rabbits.
AB  - This study was designed to quantitatively assess long-term end-to-side
      neurorrhaphy in rabbits. The cut right ulnar nerve was repaired and sutured to
      the median nerve, in which a perineurial window was created in an end-to-side
      fashion 3 cm above the elbow joint. Both the extent of the reinnervation and the
      integrity of the intact donor nerve were evaluated in 36 rabbits randomly treated
      with fresh or delayed nerve repair. Evaluations included motor nerve conduction
      velocity (MNCV), dry muscle weight (DMW), and histological examinations at 9 and
      12 months postoperatively. The recovery rates of MNCV were 90.1% and 92.8% for
      the ulnar nerve, and 95.7% and 96.8% for the median nerve, compared to intact
      contralateral nerves at 9 and 12 months, respectively. MNCV was not detectable
      for the ulnar nerve in control animals, while it was normal for the median nerve.
      Recoveries of flexor carpi ulnaris dry muscle weight of about 90.7% and 94.5%
      were observed at 9 and 12 months postoperatively, respectively. However, muscle
      mass measurements revealed a recovery of only 31.3% and 27% for control groups at
      9 and 12 months postoperatively. The differences between experimental groups and
      control groups were statistically significant (P < 0.01). Neurofilament and
      silver stains showed numerous sprouting axons originating from the median nerve
      to the ulnar nerve. The results indicate that end-to-side neurorrhaphy could
      induce axonal sprouting from the main nerve trunk of upper limbs in rabbits,
      leading to useful functional recovery.

PMID- 16628746
TI  - Musculocutaneous neurotization to restore elbow flexion in brachial plexus
      paralysis.
AB  - Brachial plexus injuries may result in devastating paralysis, especially if they
      involve all the roots. The upper roots are often traumatized, and therefore elbow
      flexion is usually lost. The prognosis of these injuries is grave if root
      avulsions are present and the paralysis includes the hand as well. The current
      management of brachial plexus injuries should be early, aggressive microsurgical
      reconstruction of the plexus, combining various neurotizations with intraplexus
      and extraplexus nerve donors. Following this principle, we present the results of
      musculocutaneous neurotization in our unit, as well as a review of the literature
      on this subject. Our results are comparable to those reported in the literature,
      and indicate that the strongest function is achieved after neurotization via
      intraplexus donors, while some extraplexus donors (i.e., phrenic and accessory
      nerve) can offer equally strong elbow flexion, especially if they are used in
      combination. Neurotization of the musculocutaneous nerve should be one of the
      primary goals in the reconstruction of the injured plexus, since the return of
      elbow flexion is of paramount importance in daily activity. The restoration of
      function is ensured if the stronger and healthier motor donors are dedicated to
      the neurotization of the musculocutaneous nerve. Sometimes in order to match the
      axonal number of the target to the lower number of axons offered by the donors,
      two or more donor nerves may be driven to the same target, such as the
      musculocutaneous nerve.

PMID- 16628747
TI  - Secondary reanimation procedures in late obstetrical brachial plexus palsy
      patients.
AB  - The varying degrees of spontaneous reinnervation that occur in untreated
      obstetrical brachial plexus palsy leave characteristic deformities of the
      shoulder, elbow, forearm, wrist, and hand. Common sequelae are internal rotation
      and adduction deformity of the shoulder, elbow flexion contractures, forearm
      supination deformity, and lack of wrist extension and finger flexion. Early
      microsurgical reconstruction of the affected plexus leads to a more rewarding
      overall function of the upper arm, but residual deformities might appear later
      which are similar, although less serious, than those observed in untreated cases.
      Secondary procedures of the shoulder, elbow, forearm, and hand will improve the
      appearance and function of the upper extremity in late cases of obstetrical
      brachial plexus. Careful preoperative planning is mandatory and a multistage
      approach should be applied, depending on the type of palsy and the age of the
      patient.

PMID- 16628748
TI  - In vivo micronuclei in uncultured T-lymphocytes of male railroad transit workers
      and referents.
AB  - In the biomonitoring of human genotoxic effects, micronuclei (MN) usually are
      scored in phytohaemagglutinin-stimulated cultured lymphocytes. MN also can be
      examined in uncultured lymphocytes, which facilitates the analysis of genotoxic
      damage incurred in vivo. Characterization of MN in cultured lymphocytes by
      fluorescence in situ hybridization (FISH) has shown a clear over-representation
      of the X and Y chromosomes in the MN of males. However, it is not known if this
      phenomenon also occurs in vivo. The purpose of the present study was to assess
      the frequency and composition of MN formed in vivo from immunomagnetically
      isolated uncultured T-lymphocytes of men. To evaluate the possible effects of
      genotoxic exposure on in vivo MN, we examined 17 railroad workers occupationally
      exposed to complex chemical mixtures and 14 referents, all nonsmokers. The
      results showed similar total frequencies of micronucleated cells among the
      exposed workers and the referents. When the MN were characterized by FISH, there
      were no significant differences between the exposed and referents with regards to
      the frequency of centromere-positive or centromere-negative MN. Centromeric label
      was observed in 69% of all MN, indicating that most of the MN contained whole
      chromosomes (or chromatids). 80% of the centromere-positive MN harbored
      autosomes, 12% Y chromosomes, and 8% X chromosomes. The occurrence of the Y- and
      X-chromosomes in MN was, respectively, 5.5- and 3.8-times greater than would be
      expected assuming an equal contribution by all chromosomes. Thus, sex chromosomes
      appear to be over-represented in lymphocyte MN of men in vivo, confirming
      previous results obtained in vitro.

PMID- 16628749
TI  - Monitoring granule formation in anaerobic upflow bioreactors using
      oligonucleotide hybridization probes.
AB  - The process of granule formation in upflow anaerobic sludge blanket (UASB)
      reactors was studied using oligonucleotide hybridization probes. Two laboratory
      scale UASB reactors were inoculated with sieved primary anaerobic digester sludge
      from a municipal wastewater treatment plant and operated similarly except that
      reactor G was fed glucose, while reactor GP was fed glucose and propionate. Size
      measurements of cell aggregates and quantification of different populations of
      methanogens with membrane hybridization targeting the small-subunit ribosomal RNA
      demonstrated that the increase in aggregate size was associated with an increase
      in the abundance of Methanosaeta concilii in both reactors. In addition,
      fluorescence in situ hybridization showed that the major cell components of small
      aggregates collected during the early stages of reactor startup were M. concilii
      cells. These results indicate that M. concilii filaments act as nuclei for
      granular development. The increase in aggregate size was greater in reactor GP
      than in reactor G during the early stages of startup, suggesting that the
      presence of propionate-oxidizing syntrophic consortia assisted the formation of
      granules. The mature granules formed in both reactors exhibited a layered
      structure with M. concilii dominant in the core, syntrophic consortia adjacent to
      the core, and filamentous bacteria in the surface layer. The excess of
      filamentous bacteria caused delay of granulation, which was corrected by
      increasing shear through an increase of the recycling rate.

PMID- 16628750
TI  - Micronucleus induction by metronidazole in rat vaginal mucosa.
AB  - Metronidazole (MTZ) is used for the treatment of many infectious diseases,
      including vaginal infections. While data indicate that MTZ is mutagenic and
      induces micronuclei in rodents, there is no information on the genotoxicity of
      MTZ in epithelial vaginal cells or cervical cells. In the present study, we have
      instilled MTZ into the vagina of rats and evaluated the micronucleus (MN)
      frequency in proestrus rat vaginal mucosal cells. The first identified proestrus
      before treatment was used to establish basal proestrus micronucleated cell (PMNC)
      frequencies. Rats then were assigned to one of five groups: a negative control,
      three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control
      treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for
      five consecutive days, vaginal cell samples were taken daily until three cycles
      of estrus were completed. Smears prepared from the samples were evaluated for
      micronuclei in proestrus cells. No differences were found between the PMNC
      frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group
      treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies
      in the first and second proestrus samples, while 5-Fu treatment produced
      significant increases in PMNC frequency in the second and third proestrus. These
      results indicate that topical administration of relatively high concentrations of
      MTZ is genotoxic in rat vaginal mucosa cells.

PMID- 16628751
TI  - Analysis of UV-stimulated recombination in the Drosophila SMART assay.
AB  - The UV component of solar radiation is classified into UVA (320-400 nm), UVB (290
      320 nm), and UVC (200-290 nm). Although all three types of UV light are capable
      of damaging biological systems, the earth's atmosphere filters out UVC, and a
      portion of UVB. In this study, we evaluated the induction of mutation and
      recombination by different wavelengths of UV light in the wing spot test of
      Drosophila melanogaster (Somatic Mutation and Recombination Test, SMART). Third
      instar larvae that were trans-heterozygous for the third chromosome recessive
      markers, multiple wing hairs (mwh) and flare-3 (flr(3)), were exposed to
      different doses of UVA (at 365 nm), UVB (at 312 nm) or UVC (at 254 nm), and
      transferred to standard Drosophila culture medium. Feeding ended with pupation of
      the surviving larvae, and the genetic changes induced in the somatic cells of the
      wing's imaginal discs lead to the formation of mutant clones on the wing blade.
      Point mutation, chromosome breakage, and mitotic recombination produce single
      spots, while twin spots are produced only by mitotic recombination. Exposure to
      500-4,000 J/cm(2) UVA did not increase the frequency of mutant spots. UVB doses
      of 200, 250, 300, 350, and 400 J/cm(2) increased the frequency of all categories
      of spots, indicating that UVB was potentially both mutagenic and recombinogenic.
      Assays run in balancer-heterozygous flies (which are insensitive to
      recombination) indicated that the fraction of mutants in trans-heterozygous flies
      due to recombination increased from 48.57% at 200 J/cm(2) UVB to 98.30% at 400
      J/cm(2) UVB. While 140-480 J/cm(2) of UVC was not genotoxic, UVC produced a
      strong toxic response at doses higher than 140 J/cm(2). The results of this study
      indicate that UVB was much more active than UVC or UVA in the SMART assay, and
      that UVB was highly recombinogenic.

PMID- 16628752
TI  - Thyroid MALT lymphoma in patients with a compressive goiter.
AB  - BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas account for less
      than 1% of all primary thyroid malignancies. They typically arise as neoplastic
      transformations within areas of autoimmune thyroiditis. Although they tend to
      have an indolent course, these lymphomas present a diagnostic challenge requiring
      a high level of suspicion in patients at increased risk of development. METHODS:
      We retrospectively reviewed 3 cases of primary MALT thyroid lymphoma discovered
      in patients with a compressive goiter. This represents the experience at a single
      institution from 1996 to 2005. Hospital and clinic records were reviewed to
      identify the workup, treatment, and outcome. RESULTS: One of 3 patients underwent
      preoperative fine-needle aspiration (FNA). All patients underwent total
      thyroidectomy to relieve compressive symptoms, and the final pathology revealed
      MALT lymphoma. Two patients subsequently underwent radiation therapy. All
      patients are alive without evidence of disease recurrence. CONCLUSIONS: These
      cases are notable for the unexpected presentation of MALT lymphoma within a
      compressive goiter.

PMID- 16628753
TI  - Identification by 19F NMR of traditional Chinese medicinal plants possessing
      prolyl oligopeptidase inhibitory activity.
AB  - Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline
      containing peptides at the carboxy termini of the proline residues. This
      peptidase has been associated with schizophrenia, bipolar affective disorder, and
      related neuropsychiatric disorders and might therefore have important clinical
      implications. Traditional Chinese medicinal (TCM) plants provide a rich source of
      unexplored compounds for strategies to find novel POP inhibitors, but the
      traditional methodologies used to identify POP inhibitors could have some
      limitations when working with natural products: interference with the
      colorimetric or fluorimetric detection methods commonly used to screen for POP
      inhibitors can result in the generation of false positives or false negatives.
      Since NMR screening is less prone to such interference, we decided to explore the
      use of 19F NMR to screen for POP inhibitors. We synthesized a new 19F-labeled POP
      substrate--Z-Gly-Pro-Phe-4(CF3)-NH2--and used it to search for new POP inhibitors
      in TCM plant extracts. We identified several plants with high POP-inhibitory
      activity and show here that the combination of 19F NMR and TCM plant extracts is
      a useful tool for identifying new POP inhibitors.

PMID- 16628754
TI  - Mapping protease substrates by using a biotinylated phage substrate library.
AB  - We describe a bacteriophage M13 substrate library encoding the AviTag (BirA
      substrate) and combinatorial heptamer peptides displayed at the N terminus of the
      mature form of capsid protein III. Phages are biotinylated efficiently (> or =
      50%) when grown in E. coli cells coexpressing BirA, and such viral particles can
      be immobilized on a streptavidin-coated support and released by protease cleavage
      within the combinatorial peptide. We have used this library to map the
      specificity of human Factor Xa and a neuropeptidase, neurolysin (EC3.4.24.16).
      Validation by analysis of isolated peptide substrates has revealed that
      neurolysin recognizes the motif hydrophobic-X-Pro-Arg-hydrophobic, where Arg
      hydrophobic is the scissile bond.

PMID- 16628755
TI  - Identification of lipoxygenase inhibitory peptides from beta-casein by using SPOT
      synthesis.

PMID- 16628756
TI  - Dissection of conformationally restricted inhibitors binding to a beta
      glucosidase.

PMID- 16628757
TI  - Lewis base catalyzed Mannich-type reactions between trimethylsilyl enol ethers
      and aldimines.
AB  - Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and
      N-tosylaldimines is described. Nitrogen anions generated from amides or imides
      such as lithium benzamide or potassium phthalimide are found to be effective
      Lewis base catalysts in DMF at room temperature to afford the corresponding beta
      amino carbonyl compounds in good to high yields; the oxygen anion generated from
      carboxylic acids such as lithium acetate was also found to be effective in dry
      DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between
      aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene
      acetal proceeded smoothly even in water-containing DMF. Then, Lewis base
      catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide,
      and aromatic aldehyde having electron-withdrawing group such as p
      nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford
      the corresponding beta-amino ester in good yield. Further, ammonium carboxylates
      such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to
      be more effective Lewis base catalysts in the above-mentioned Mannich-type
      reaction. The synthesis proceeded in various solvents at lower temperatures. The
      reaction between aldimines and TMS enol ethers generated from thioester and
      various ketones such as propiophenone or cyclohexanone also proceeded smoothly to
      afford the corresponding beta-amino carbonyl compounds in high yields with good
      to high anti-selectivities.

PMID- 16628758
TI  - Ultrafast excited-state excitation dynamics in a quasi-two-dimensional light
      harvesting antenna based on ruthenium(II) and palladium(II) chromophores.
AB  - A detailed study on the excited-state-excitation migration taking place within
      the tetranuclear complex [{(tbbpy)(2)Ru(tmbi)}(2){Pd(allyl)}(2)](PF(6))(2) (tbbpy
      = 4,4'-di-tert-butyl-2,2'-bipyridine and tmbi = 5,6,5',6'-tetramethyl-2,2'
      bibenzimidazolate) is presented. The charge transfer is initiated by the
      photoexcitation into the lowest metal-to-ligand charge-transfer (MLCT) band of
      one of the peripheral ruthenium(II) chromophores and terminates on the central
      structurally complex Pd(2) (II)(allyl)(2) subunit. Thus, the system under
      investigation can be thought of as a functional model for the photosynthesis
      reaction center in plants. The kinetic steps involved in the overall process are
      inferred from femtosecond time-resolved transient-grating kinetics recorded at
      spectral positions within the regions of ground-state bleach and transient
      absorption. The kinetics features a complex non-exponential time behavior and can
      be fitted to a bi-exponential rise (tau(1)> or =200 fs, tau(2) approximately 1.5
      ps) and a mono- or bi-exponential decay, depending on the experimental situation.
      The data leads to the formulation of a model for the intramolecular excitation
      hopping ascribing intersystem crossing and subsequent cooling as the two fastest
      observed processes. Following these initial steps, charge transfer from the
      ruthenium to the central complex Pd(2)(allyl)(2) moiety is observed with a
      characteristic time constant of 50 ps. A 220-ps component that is observed in the
      ground-state recovery only is attributed to excitation equilibration between the
      two identical Pd(allyl) chromophores.

PMID- 16628759
TI  - Optical, redox, and NLO properties of tricyanovinyl oligothiophenes: comparisons
      between symmetric and asymmetric substitution patterns.
AB  - A series of tricyanovinyl (TCV)-substituted oligothiophenes was synthesized and
      investigated with a number of physical methods including UV/Vis, IR, and Raman
      spectroscopy, nonlinear optical (NLO) measurements, X-ray diffraction, and cyclic
      voltammetry. Mono- or disubstituted oligomers were prepared by the reaction of
      tetracyanoethylene with mono- or dilithiated oligomers. The comparative effects
      of the symmetric and asymmetric substitutions in the electronic and molecular
      properties have been addressed. These oligomers display dramatic reductions in
      both their optical and electrochemical band gaps in comparison with unsubstituted
      molecules. The analysis of the electronic properties of the molecules was
      assisted by density functional theory calculations, which are in excellent
      agreement with the experimental data. TCV substitution influences the energies of
      the frontier orbitals, especially with respect to the stabilization of LUMO
      orbitals. X-ray structural characterization of a monosubstituted oligomer
      exhibits pi-stacking with favorable intermolecular interactions. NLO results
      agree with the role of the intramolecular charge-transfer feature in the
      asymmetric samples. These results furthermore exalt the role of conformational
      flexibility in the disubstituted compounds and reveal an unexpected nonlinear
      optical activity for symmetric molecules. Regarding the electronic structure, the
      interpretation of the vibrational data reflects the balanced interplay between
      aromatic and quinoid forms, finely tuned by the chain length and substitution
      pattern. The electronic and structural properties are consistent with the
      semiconducting properties exhibited by these materials in thin film transistors
      (TFTs).

PMID- 16628760
TI  - Preparation of highly conductive, self-assembled gold/polyaniline nanocables and
      polyaniline nanotubes.
AB  - One-dimensional gold/polyaniline (Au/PANI-CSA) coaxial nanocables with an average
      diameter of 50-60 nm and lengths of more than 1 mum were successfully synthesized
      by reacting aniline monomer with chlorauric acid (HAuCl(4)) through a self
      assembly process in the presence of D-camphor-10-sulfonic acid (CSA), which acts
      as both a dopant and surfactant. It was found that the formation probability and
      the size of the Au/PANI-CSA nanocables depends on the molar ratio of aniline to
      HAuCl(4) and the concentration of CSA, respectively. A synergistic growth
      mechanism was proposed to interpret the formation of the Au/PANI-CSA nanocables.
      The directly measured conductivity of a single gold/polyaniline nanocable was
      found to be high (approximately 77.2 S cm(-1)). Hollow PANI-CSA nanotubes, with
      an average diameter of 50-60 nm, were also obtained successfully by dissolving
      the Au nanowire core of the Au/PANI-CSA nanocables.

PMID- 16628761
TI  - Synthesis, structure, and reactivity of palladacycles that contain a chiral
      rhenium fragment in the backbone: New cyclometalation and catalyst design
      strategies.
AB  - The bromocyclopentadienyl complex [(eta5-C5H4Br)Re(CO)3] is converted to racemic
      [(eta5-C5H4Br)Re(NO)(PPh3)(CH2PPh2)] (1 b) similarly to a published sequence for
      cyclopentadienyl analogues. Treatment of enantiopure (S)-[(eta5
      C5H5)Re(NO)(PPh3)(CH3)] with nBuLi and I2 gives (S)-[(eta5
      C5H4I)Re(NO)(PPh3)(CH3)] ((S)-6 c; 84 %), which is converted (Ph3C+ PF6 -, PPh2H,
      tBuOK) to (S)-[(eta5-C5H4I)Re(NO)(PPh3)(CH2PPh2)] ((S)-1 c). Reactions of 1 b and
      (S)-1 c with Pd[P(tBu)3]2 yield [{(eta5-C5H4)Re(NO)(PPh3)(mu-CH2PPh2)Pd(mu-X)}2]
      (10; X = b, Br, rac/meso, 88 %; c, I, S,S, 22 %). Addition of PPh3 to 10 b gives
      [(eta5-C5H4)Re(NO)(PPh3)(mu-CH2PPh2)Pd(PPh3)(Br)] (11 b; 92 %). Reaction of (S)
      [(eta5-C5H5)Re(NO)(PPh3)(CH2PPh2)] ((S)-2) and Pd(OAc)(2) (1.5 equiv; toluene,
      RT) affords the novel Pd3(OAc)4-based palladacycle (S,S)-[(eta5
      C5H4)Re(NO)(PPh3)(mu-CH2PPh2)Pd(mu-OAc)2Pd(mu-OAc)2Pd(mu
      PPh2CH2)(Ph3P)(ON)Re(eta5-C5H4)] ((S,S)-13; 71-90 %). Addition of LiCl and LiBr
      yields (S,S)-10 a,b (73 %), and Na(acac-F6) gives (S)-[(eta5-C5H4)Re(NO)(PPh3)(mu
      CH2PPh2)Pd(acac-F6)] ((S)-16, 72 %). Reaction of (S,S)-10 b and pyridine affords
      (S)-[(eta5-C5H4)Re(NO)(PPh3)(mu-CH2PPh2)Pd(NC5H5)(Br)] ((S)-17 b, 72 %); other
      Lewis bases yield similar adducts. Reaction of (S)-2 and Pd(OAc)2 (0.5 equiv;
      benzene, 80 degrees C) gives the spiropalladacycle trans-(S,S)-[{(eta5
      C5H4)Re(NO)(PPh3)(mu-CH2PPh2)}2Pd] (39 %). The crystal structures of (S)-6 c, 11
      b, (S,S)- and (R,R)-132 C7H8, (S,S)-10 b, and (S)-17 b aid the preceding
      assignments. Both 10 b (racemic or S,S) and (S)-16 are excellent catalyst
      precursors for Suzuki and Heck couplings.

PMID- 16628762
TI  - Rapid room temperature Buchwald-Hartwig and Suzuki-Miyaura couplings of
      heteroaromatic compounds employing low catalyst loadings.
AB  - The use of second-generation [(NHC)Pd(R-allyl)Cl] complexes for Suzuki-Miyaura
      and Buchwald-Hartwig cross-coupling reactions involving heteroaromatic halides at
      room temperature is reported. The first examples of room temperature Suzuki
      Miyaura cross-coupling of deactivated aryl chlorides with alkenyl boronic acids
      are also disclosed. Terminal substitution at the allyl moiety of the palladium
      complex facilitates its activation at room temperature leading to very active
      catalytic species enabling the present catalytic transformations to be performed
      rapidly using very mild reaction conditions. Catalyst loadings can be as low as
      10 ppm for the Buchwald-Hartwig aryl amination and 50 ppm for the Suzuki-Miyaura
      reaction.

PMID- 16628766
TI  - From subphthalocyanines to subporphyrins.

PMID- 16628767
TI  - Reactions at very low temperatures: gas kinetics at a new frontier.
AB  - Advances in experimental techniques, especially the development of the CRESU
      (Cinetique de Reaction en Ecoulement Supersonique Uniforme) method, allow many
      gas-phase molecular processes to be studied at very low temperatures. This Review
      focuses on the reactions of molecular and atomic radicals with neutral molecules.
      Rate constants for almost 50 such reactions have been measured at temperatures as
      low as 13 K by using the CRESU method. The surprising demonstration that so many
      reactions between electrically neutral species can be extremely rapid at these
      very low temperatures has excited interest both from theoreticians and from those
      seeking to understand the chemistry that gives rise to the 135 or so molecules
      that are present in low-temperature molecular clouds in the interstellar medium.
      Theoretical treatments of these reactions are based on the idea that a reaction
      occurs when the long-range potential between the reagent species brings them into
      close contact. The astrochemical context, theoretical studies, and the
      determination of the rate constants of these low-temperature reactions are
      critically discussed.

PMID- 16628768
TI  - Efficient route to tetramethylalumoxane and carboxylate alumoxanes through the
      alkylation of phthalic acid.

PMID- 16628769
TI  - Phase I AIDS vaccine trial opens in India.

PMID- 16628770
TI  - Trial shows HSV-2 suppression can reduce HIV shedding.

PMID- 16628771
TI  - Disputing taste: food pleasure as an achievement in interaction.
AB  - While identity has been a dominant topic in research on food choice, literature
      on identity in consumers' everyday life is scarce. In this article we draw on
      insights from discursive psychology to demonstrate how members of an online forum
      on food pleasure handle the hedonic appreciation of food in everyday interaction.
      We examined 40 discussions consisting of 1715 e-mails related to culinary topics.
      The analysis focuses on the way in which the participants of this forum work up
      and establish their identities as "gourmets". A dominant tool in performing this
      identity work is the discursive construction of independent access to knowledge
      of and experience with food items, so as to compete with or resist the epistemic
      superiority of a preceding evaluation. Data are presented with nine examples of
      the 73 manifestations of the construction of independent access. Contrary to
      sensory approaches to food choice, this study depicts the enjoyment of food as an
      interactional achievement rather than a pure physiological sensation. Wider
      implications of this study for the relation between food, identity and taste are
      discussed.

PMID- 16628827
TI  - World Federation of Neurology position paper on human stem cell research.

PMID- 16628828
TI  - Common ground on the critical path.

PMID- 16628829
TI  - Controversial Chinese gene-therapy drug entering unfamiliar territory.

PMID- 16628830
TI  - Funding for accelerating drug development initiative critical.

PMID- 16628831
TI  - Grace periods and patentability.

PMID- 16628832
TI  - An audience with... Sir Michael Rawlins.

PMID- 16628833
TI  - The GERD market.

PMID- 16628835
TI  - Paxil: part of the process.

PMID- 16628834
TI  - Sunitinib maleate.

PMID- 16628836
TI  - Friends in high places.

PMID- 16628837
TI  - Relative timing of redistribution of cytochrome c and Smac/DIABLO from
      mitochondria during apoptosis assessed by double immunocytochemistry on mammalian
      cells.
AB  - Redistribution of cytochrome c and Smac/DIABLO from mitochondria occurs during
      apoptosis, although the relative timing of their release is not well
      characterized. Double immunocytochemistry was utilized here to study
      quantitatively the patterns of release of cytochrome c and Smac/DIABLO from
      mitochondria in single cells. Human osteosarcoma cells and murine embryonic
      cortical neurons were analyzed during apoptosis induced by staurosporine. In
      osteosarcoma cells treated with staurosporine for 24 h, a substantial proportion
      of cells (36%) released cytochrome c from the mitochondria before Smac/DIABLO. In
      contrast, these proteins were released mostly concordantly in neurons; only a
      minority of cells (< or = 15%) released cytochrome c without Smac/DIABLO (or vice
      versa) from mitochondria. Patterns of release in either cell type were unaltered
      by addition of the caspase inhibitor, zVAD-fmk. The double immunocytochemistry
      procedure facilitated clear definition of the temporal release of cytochrome c
      and Smac/DIABLO from mitochondria in intact apoptotic cells, enabling us to
      demonstrate for the first time that their mutual redistribution during apoptosis
      varies between different cell types.

PMID- 16628838
TI  - [Restless times in German hospitals].

PMID- 16628839
TI  - Acetaminophen alert.

PMID- 16628840
TI  - [Transformation in the hospital landscape from the viewpoint of public accident
      insurers].

PMID- 16628841
TI  - [Perspectives for comprehensive emergency surgical coverage].

PMID- 16628842
TI  - Joseph R. Bove, MD: Autobiography.

PMID- 16628843
TI  - The new food guide pyramid: what's the message?

PMID- 16628844
TI  - On the road again. Food fit for traveling.

PMID- 16628845
TI  - Eye disease. Understanding retinopathy, Part 2.

PMID- 16628847
TI  - Disaster strikes. Are you ready?

PMID- 16628846
TI  - Fighting the fear. Pay attention to your diabetes.

PMID- 16628848
TI  - Dodging disaster. Hurricane Katrina struck New Orleans like a battering ram, but
      Sid Seruntine was ready.

PMID- 16628849
TI  - Winter soup--the perfect meal. These easy recipes are just the thing to warm you
      up when it's cold outside.

PMID- 16628850
TI  - Research profile. Exercise. Can it help you think? Laura Dehaven Baker, MA, PhD.

PMID- 16628851
TI  - Watch your mouth. Diabetes and dental care.

PMID- 16628852
TI  - B vitamins are vital. Get yours every day.

PMID- 16628853
TI  - Better blood glucose? You bet!
AB  - Good blood glucose control can seem like a lofty goal. But if you take it one
      step at a time, you can achieve it. Here, the experts show you how.

PMID- 16628854
TI  - A dedication to life. The Cleveland brothers have had diabetes for 145 years
      between them, and they're still going strong.

PMID- 16628855
TI  - All about wound care. If you have a wound on your foot, don't ignore it. The care
      you seek today can prevent an amputation tomorrow.

PMID- 16628856
TI  - Take charge of your meds. Here's how to make your medications work for you.

PMID- 16628857
TI  - Go fish! Try these great seafood suppers.

PMID- 16628858
TI  - Living through menopause. Women go through many transitions in their lives, and
      diabetes affects how they experience a lot of them. Menopause--the time when
      periods stop--is no exception.

PMID- 16628859
TI  - Research profile. From the inside out. Heart disease and diabetes. Steven P.
      Marso, MD.

PMID- 16628860
TI  - The real threat of litigation.

PMID- 16628861
TI  - The cost of negligence.

PMID- 16628862
TI  - Re: Art, dreams and active imagination: a post-Jungian approach to transference
      and the image.

PMID- 16628863
TI  - Re: Art, dreams and active imagination: a post-Jungian approach to transference
      and the image.

PMID- 16628864
TI  - An unusual cause of hemorrhagic left pleural effusion.

PMID- 16628865
TI  - Suspected adverse reactions, 2005.

PMID- 16628866
TI  - Perceiving events as both inevitable and unforeseeable in hindsight: the Leipzig
      candidacy for the Olympics.
AB  - We present a new conceptualization of hindsight bias in terms of three separate
      hindsight components (foreseeability impressions, perceptions of necessity and
      memory distortions) and report three kinds of supporting evidence from an
      internet study (N = 101) of the unsuccessful application of the City of Leipzig
      to host the Olympic Games: (1) strongly diverging hindsight effects, (2) low
      intercorrelations between the components, and (3) dissociative effects of third
      variables on them. Specifically, experiencing the failure of the application as
      personally negative (due to a pro-application attitude and previous commitment),
      led to perceiving it as inevitable but also as unforeseeable. This surprising
      result helps to resolve seeming contradictions between previous findings (Louie,
      1999; Mark et al., 2003; Tykocinski, 2001) by relating the opposite hindsight
      effects to differences in the nature and functions (dissonance reduction vs.
      coping with disappointment) of the foreseeability and necessity components.

PMID- 16628867
TI  - A study of the factors that influence how senior officers police crowd events: on
      SIDE outside the laboratory.
AB  - This paper fits into the SIDE perspective (Reicher, Spears, & Postmes, 1995;
      Postmes, Spears, Lea, & Reicher, 2000), which emphasises the importance of
      integrating the cognitive and strategic dimensions of group processes. Our study
      examines the decisions made by senior police officers during a simulation
      exercise of a crowd event. The analysis shows, firstly, that officers are deeply
      concerned about their accountability to a variety of audiences, both internal and
      external to the police force. Second, these different audiences pressure them to
      act in different, and sometimes contradictory, ways. What counts, then, is the
      overall balance between accountability concerns. Third, this balance - and, with
      it, police perceptions and decisions - alters in the course of an event. More
      specifically, with escalating conflict, the balance of accountability concerns
      moves increasingly in the direction of undifferentiated intervention against
      crowd members. In discussion, we consider both the theoretical implications of
      this analysis for research on group processes (in particular the importance of
      accountability issues once one moves beyond the laboratory and deals with groups
      that have a past and future and in which membership is more than simply an act of
      choice) and the practical implications in terms of crowd policing.

PMID- 16628868
TI  - Animal use in biomedicine: an annotated bibliography of Buddhist and related
      perspectives.

PMID- 16628869
TI  - A nurse's recovery story.

PMID- 16628870
TI  - 1986--1996 rural health, nursing specialties and individual accomplishment.

PMID- 16628871
TI  - NNA member a fixture in rural health care landscape.

PMID- 16628872
TI  - Making Medicare make sense.

PMID- 16628873
TI  - Jorge Juarez, 41-year-old nursing student overcomes major personal obstacles to
      be a nurse.

PMID- 16628874
TI  - Limitation of medical research in German law.
AB  - In Germany, pharmaceutical trials and the testing of medical devices is regulated
      by statute. Any other kind of medical experimentation is handled according to the
      Declaration of Helsinki. Medical experimentation has to be reviewed by an ethics
      committee before the start and there has to be an elaborate research protocol,
      which provides for the protection of the experimental subject. In case of an
      accident, there is compulsory accident insurance as far as pharmaceutical trials
      and the testing of medical devices are concerned. The third party accident
      insurance just covers material loss, there is no provision paying and suffering.
      The sum paid by the insurance company is set off against damages for negligence.
      There is no strict liability for medical experimentation, but the German courts
      are expected to set very high standards for medical care in experimentation. The
      data protection and medical confidentiality have been lessened because of the
      European law that requires the experimental subject to give his consent to the
      inspection of the data or the file and if he takes part in the experimentation,
      that his data and some of his cells might be with the pharmaceutical company
      forever. In general, the German law seems to be adequate to the protection of
      experimental subjects.

PMID- 16628875
TI  - [Thoughts about a model of constitutional articulation of the public power in the
      field of biomedical sciences].
AB  - This article analyses from a substantive and organizational point of view the
      current scope of competence of the Spanish public powers in the field of
      biomedical sciences. The general rule is established whereby the competence
      belongs to the State. The autonomous communities opt for silence, except for
      exceptional cases (Cantabria, Cataluna, Madrid). Given this situation coupled
      with the lack of rulings by the Consitutional Tribunal on the possible conflicts
      that could arise between an autonomous community and the State in the field of
      biomedical sciences, Profesor Fonseca correctly concludes that there is a need to
      draft an express distribution of competences between the different public powers
      in this matter.

PMID- 16628876
TI  - [Judicial-biotechnological system and the right to life: an approximation from
      the European and Spanish law].
AB  - This work consists in the systemisation of the complex and diversified of the
      group of normative regulations of life, of all life. This is based on the
      premises that it is a core value as a principle and a right and overcoming its
      static and predetermined conception, replacing it with a new, dynamic, individual
      and creative vision. Life, as a legal fact, is the basic idea in a wide legal
      regulation, that, notwithstanding the diversity and mobility of the norms
      relative to human, animal and vegetable life should be redirected at last
      instance towards a common and unitary legal status.

PMID- 16628877
TI  - [Legal protection of the genetic heritage in Brazil (comments on the new
      "Biosafety Law" of March 24, 2005)].
AB  - The purpose of the current article is to outline and comment the most important
      aspects of the regulation of Brazil's criminal legislation about the protection
      of the human genome, which establishes crimes related to genetic manipulation and
      to the dissemination of transgenics in the environment. It also refers to the
      problems related to the application of the old legal text (Law 8.974/1995), which
      punished conducts that stayed without the enough development. These gaps
      complicated so much the application of those rules that the Brazilian Parliament
      has recently proposed the complete modification of the present legislation by a
      new Biosecurity Law (Law 11.105/2005). This law for the first time authorizes
      research with human embrionyc stem cells in Brazil, trying thus to solve in this
      way the problem of cryoconserved human embryos produced by in vitro fertilization
      programmes. The new law is analyzed here from a legal and ethical view point.

PMID- 16628878
TI  - The status of the extracorporeal embryo in German law (part. II).
AB  - The legislator, in the German Federal Republic, has opted for a specific legal
      solution in relation to the protection of the embryo. Carola Muller, in this
      article, describes this regulation as well as the reasons that have led to its
      adoption. The article finishes with an exposition of the existing social
      discussion in German society and the effect that the law has had.

PMID- 16628879
TI  - Gene tests and employees in an international comparison.
AB  - In this research, Professor Jurgen Simon and Christian Ravenstein have
      highlighted the general existing prohibition, in the labour field, of the
      undertaking of genetic tests that could mean discrimination for the genetic
      heritage of the worker. They have made a comparative study of several member
      States of the EU that have specific regulation on this area.

PMID- 16628880
TI  - [Judicial intervention of the DNA test (comment on decisions of the Second
      Chamber of the Supreme Court No. 501/2005, of April 19, 2005, and No. 1311/2005,
      of October 14, 2005)].
AB  - The controversy has been arisen by the Spanish Supreme Court in two recent
      judgments, as they clearly show the lack of a unique criterion in the Spanish
      jurisprudence when genetic data have to be analysed in the course of a criminal
      process, in order to identify a person. The DNA proof cannot be practised without
      judicial intervention under Spanish law.

PMID- 16628881
TI  - [DNA: a genetic tsunami that devastated the procedure formality. The new
      filiation process. In the name of the father].
AB  - This article highlights the importance that the paternal attribution has had
      historically. The author makes a comment on the Peruvian law 28457 of 8 January
      2005 where a new extraordinary process to investigate the extramarital paternity
      is established

PMID- 16628882
TI  - Report on genetically modified organisms in agriculture and food.

PMID- 16628883
TI  - [Peruvian law regulating the judicial filiation process in extramarital
      paternity].

PMID- 16628884
TI  - Universal Declaration on Bioethics and Human Rights.

PMID- 16628885
TI  - [References to books, articles in periodicals and to other documents].

PMID- 16628886
TI  - The effect of undersowing cabbage with white clover on thrips infestation and
      flight activity.
AB  - In 2001-2003, the levels of infestation of thrips in cabbage monocrops and
      cabbage/white clover intercrops were compared. The flight activity of thrips was
      monitored using blue sticky traps and white water traps to obtain a better
      understanding of population dynamics of thrips. Plant samples were taken to
      record the number of thrips on cabbage. Over the years of observations, the
      highest number of thrips was collected in blue sticky traps on cabbage undersown
      with white clover. In the period from 15th June to 5th July 2001, the number of
      thrips collected in blue sticky traps in the monocropped cultivation and
      intercrops with white clover was on similar low levels. Next, the number suddenly
      increased to 372 thrips/trap in monocropped cultivation and 509 thrips/trap in
      the intercropped cultivation. During the period of the highest peak of thrips
      activity, which was on 17th July, there were 650 thrips/trap and nearly the same
      number was noticed for both types of cultivations. After this period, until the
      end of vegetation, the greater number of thrips was noticed for the traps placed
      in the intercrops. Additionally, in 2001 the thrips were collected in white water
      traps. Using this type of traps, 480 total thrips/trap were collected in the
      monocropped cultivation and 819/thrips/trap in the intercrops during the whole
      vegetation season. The percentage participation of Thrips tabaci Lind. caught in
      white water traps was 24.4% in the monocropped cultivation and 15.4% in the
      intercrops. In 2002, during the period from the middle of June to the third
      decade of July, significantly higher number of thrips was collected in blue
      sticky traps placed in the cabbage with white clover. The number of thrips
      collected during the period of the mass flights, which means in the first decade
      of July was over twice as many thrips in the traps placed in the intercropped
      cultivation (1316 thrips/trap) as in the monocropped cultivation (589
      thrips/trap). In 2003, during the whole vegetation period, the number of thrips
      collected in blue sticky traps placed on the plots where cabbage was cultivated
      with white clover was evidently higher. In this year two peaks of the thrips
      flight activity were recorded: the first on 16th July and the second on 5th
      August. On both occassions, the number of thrips collected in blue sticky traps
      placed in the intercropped cultivations was about twice as high as in the
      monoculture cultivation. In 2001-2003, the thrips feeding on cabbage in the
      monocropped and intercropped cultivations were observed mainly in July and once
      again in August. The number of thrips on cabbage was low, only in 2002 this
      number was higher. In 2001, the number of thrips on cabbage in both types of
      cultivations was on similar level. The highest number of thrips was observed
      during the peak of thrips flight activity, which was in the middle of July. In
      years 2002-2003, despite the higher number of thrips collected in blue sticky
      traps placed in the intercropped cultivations, the number of pests collected from
      the cabbage undersown with white clover was lower than in the monocropped
      cultivation. In 2002, the period of the most intensive occurrence of thrips on
      cabbage was overlapping with the period of mass flight activity of thrips. During
      this period, a little higher number of thrips was noticed on cabbage in the
      intercropped cultivation (3.4 thrips/plant) than in the monocropped cultivation
      (3.2 thrips/plant). In 2003, the highest number of thrips on cabbage in both
      types of cultivations was noticed before the first significant peak of thrips
      flight activity. Whereas in the first decade of August, when the same high number
      of thrips collected in blue sticky traps was again noticed, no increase in the
      number of thrips feeding on cabbage was observed in both type of cultivations.
      Over all years of observations, despite the higher number of thrips collected in
      blue sticky traps in the intercropped cultivation, this number was always lower
      on the cabbage undersown with white clover. The most dominant species in both
      cultivations was Thrips tabaci Lind. Its percentage participation in the
      collected material was 83.1% in the monocropped cultivation and 76.6% in the
      intercropped cultivation.

PMID- 16628887
TI  - The use of common elder Sambucus nigra to promote Aphidophagous syrphids in apple
      orchards.
AB  - Elder shrubs (Sambucus nigra L.) were planted in an experimental apple orchard as
      bordering hedgerow with the objective of rearing syrphids (Diptera: Syrphidae)
      and consequently enhancing the biological control of the rosy apple aphid
      Dysaphis plantaginea (Passerini). The inoculative introduction of the specific
      elder aphid Aphis sambuci L. (Homoptera: Aphididae) in late March 2002 and again
      in 2003 led to the complete hedgerow turning into an early and productive
      alternative prey reservoir for indigenous syrphids. The species Scaeva pyrastri
      (L.), S. selenetica (Meigen), Syrphus ribesii (L.), S. vitripennis Meigen,
      Epistrophe eligans (Harris), E. nitidicollis (Meigen), Platycheirus scutatus
      (Meigen), Eupeodes corollae (F.), Meligramma triangulifera (Zetterstedt) and
      Episyrphus balteatus (De Geer) developed on the elder hedgerow during the spring
      2002 taking advantage of the aphid infestation. The season 2003 was characterised
      by a quite different species abundance pattern as, contrary to the previous year
      when both monovoltine and polyvoltine species were equally represented, the
      monovoltine syrphids (Epistrophe spp.) represented the dominant group exploiting
      the elder aphids. A parallel analysis showed that the faeces of the first adult
      syrphids observed ovipositing on the elder hedgerow in spring contained digested
      pollen of mainly apple. Our observations indicate the possibility of establishing
      a local population of monovoltine syrphids in apple orchards by managing an aphid
      infested elder hedgerow, without any additional pollen or nectar producing
      plants.

PMID- 16628888
TI  - Aphid parasitoid complex in potato in the context of IPM in Belgium.
AB  - Parasitic hymenoptera of potato aphids were collected and identified in 2000 and
      2001 in 11 potato fields in Belgium. Nine Aphidiidae species, parasiting seven
      aphid species, were found: Aphidius ervi, Aphidius matricariae, Aphidius picipes,
      Binodoxys angelicae, Diaeretiella rapae, Praon abjectum, Praon gallicium, Praon
      volucre and Toxares deltiger. A. ervi and A. picipes were the dominant and sub
      dominant species, with 54% and 28% of the primary parasite collected,
      respectively. Both species and T. deltiger were found on Aphis nasturti,
      Aulacorthum solani, Macrosiphum euphorbiae and Myzus persicae, the four most
      important aphid potato in Belgium. Parasitism rate of A. nasturtii and, to a
      lesser extent, M. euphorbiae was low compared to A. solani and M. persicae.
      Parasitism of A. solani was particularly high, with 63.5% in 2000 and 89.2% in
      2001, and this species was the preferred host of several Aphidiid species. The
      abundance of alternative hosts as other crops pest aphids or non-pest aphids on
      wild plants in agroecosystems could explains the efficacy of these species. The
      biological control of A. nasturtii and M. euphorbiae by parasitic hymenoptera was
      poorer, and several studies need to be undertaken to find suitable parasitic
      hymenoptera species effective on these aphids and agro-environmental measures
      able to promote them.

PMID- 16628889
TI  - Selectivity lists of pesticides to beneficial arthropods for IPM programs in
      carrot--first results.
AB  - In order to improve IPM programs in carrot, 7 fungicides, 12 herbicides and 9
      insecticides commonly used in Belgium were tested for their toxicity towards five
      beneficial arthropods representative of most important natural enemies
      encountered in carrot: parasitic wasps - Aphidius rhopalosiphi (De Stefani-Perez)
      (Hym., Aphidiidae), ladybirds - Adalia bipunctata (L.) (Col., Coccinellidae),
      hoverfly - Episyrphus balteatus (Dipt.. Syrphidae), rove beetle - Aleochara
      bilineata (Col., Staphylinidae) and carabid beetle - Bembidion lampros (Col.,
      Carabidae). Initialy, all plant protection products were tested on inert
      substrate glass plates or sand according to the insect. Products with a corrected
      mortality (CM) or a parasitism reduction (PR) lower than 30% were kept for the
      constitution of positive list (green list). The other compounds were further
      tested on plant for A. rhopalosiphi, A. bipunctata, E. balteatus and soil for B.
      lampros and A. bilineata. With these extended laboratory tests results, products
      were listed in toxicity class: green category [CM or PR < or = 30%], yellow
      category [30% < CM or PR < or = 60%] and orange category [60% < CM or PR < or =
      80%]. Products with toxicity higher than 80% on plants or that reduce parasitism
      more than 80% on soil were put in red category and are not recommended to
      Integrated Pest Management programs in carrot. Results showed that all fungicides
      tested were harmless to beneficials except Tebuconazole, which was slightly
      harmful for A. bipunctata. Herbicides were also harmless for soil beneficials,
      except Chlorpropham. This product was very toxic on sand towards A. bilineata and
      must be tested on soil. All soil insecticides tested were very toxic for ground
      beneficials and considered as non-selective. Their use in IPM is subject to
      questioning in view of negative impacts on beneficials. Among foliar
      insecticides, Dimethoate and Deltamethrin are not recommended for IPM because
      their high toxicity for all beneficials. The other foliar insecticides were more
      selective; any of them were harmless for all species tested.

PMID- 16628890
TI  - Field studies to determine mancozeb based spray programmes with minimal impact on
      predatory mites in European vine cultivation.
AB  - Mancozeb is an ethylene bisdithiocarbamate (EBDC) fungicide with contact activity
      against a wide range of economically important fungal diseases. Its multi-site
      mode of action means that to date there have been no recorded incidences of
      resistance developing despite many years of use on high risk diseases. One such
      disease, Grape downy mildew (Plasmopara viticola) has developed resistance to a
      number of important oomycete specific fungicides following their introduction
      onto the market. The role of Mancozeb either as a mixing or alternation partner
      in helping to manage these resistance situations remains critically important.
      Historical use patterns for mancozeb in tree and vine crops involved many
      applications of product at high use rates. Although this gave excellent disease
      control, a negative impact on predatory mites has been reported by researchers.
      This has lead to the development of mancozeb spray programmes in vines and other
      crops with a much reduced impact on predatory mites. A range of field studies was
      conducted in France, Germany, Italy, Portugal and Spain where either 2 or 4
      applications of mancozeb containing products were made per season at different
      spray timings. These trials covered the representative range of uses, agronomic
      practices, mite species and geographical locations in Europe. In this paper
      findings from ten field studies in five different vine growing regions in Europe
      indicated that two to four applications of mancozeb at 1.6 kg a.i./ha as part of
      a spray programme caused minimal impact on naturally occurring populations of
      predatory mites which in turn was compatible with Integrated Pest Management
      programmes and the conservation of predatory mites.

PMID- 16628891
TI  - The safety of thiamethoxam to pollinating bumble bees (Bombus terrestris L.) when
      applied to tomato plants through drip irrigation.
AB  - Thiamethoxam, mainly sold under the trademark of Actara, is a neonicotinoid
      widely used in covered vegetables for the control of aphids and whiteflies. In
      these crops, and particularly in covered tomatoes, bumble-bees are used for cross
      pollination as an alternative to labour intensive manual techniques. In this
      study, made on tomatoes grown in separated greenhouse plots in Murcia, Southern
      Spain, thiamethoxam was applied through drip irrigation at a rate of 200 g ai/ha,
      and as a split application of the same rate, to evaluate the effects on
      pollinating bumble bees compared to a foliar application of a toxic standard. The
      results showed that the toxic foliar standard had a clear effect on the
      pollination of tomato flowers, declining to zero pollination two weeks after
      application, whereas both the single and split drip irrigation applications of
      Actara had no effect on pollination when compared to the control plots. The count
      of dead adults and larvae did not show any differences between the treatments,
      whereas the measurement of sugar water consumption was shown to correlate well
      with pollination. The consumption of sugar water declined in the toxic standard
      plots by 69% with respect to the control, whilst the decline in lower dose drip
      irrigation application was only 3%. In regard to hive weight, and number of
      adults and brood after destructive sampling; there were no statistical
      differences between the treatments but a negative effect of the foliar treatment
      was observed. Based on these results we can conclude that a split application of
      Actara applied in drip irrigation to the soil/substrate has no effect on the
      bumble-bees used in tomatoes for pollination.

PMID- 16628892
TI  - Role of host plant alternation in the precocity and intensity of parasitoid
      activity on of cereal aphids.
AB  - Integrated pest management programs tend to reduce the chemical input by
      enhancing the development of biological control. Cereal aphids cause important
      damages to winter wheat in Europe but are currently under the pressure of several
      parasitoid species (Braconidae: Aphidiinae). Previous ecological studies have
      reported the existence of an asynchrony between aphid and parasitoid populations
      in early spring in cereal cultures. Here, we tested the presence of rose bushes
      (Rosa rugosa) as a host plant for alternative aphid-host. Aphid and parasitoid
      densities were recorded for two years using the plant cutting sampling method.
      The main results were: (i) rose bushes constitute a potential reservoir of
      alternative aphid hosts species for a number of parasitoid and predator species,
      (ii) rose aphids appear earlier in spring and were more abundant than the aphids
      on wheat, (iii) parasitism activity in rose bushes is synchronized with cereal
      fields, however (iv) rose bushes management did not induce a decrease of cereal
      aphid population.

PMID- 16628893
TI  - Susceptibility to abamectin of pear Psylla populations collected from Spain,
      Italy and France. European baselines, 2004.

PMID- 16628894
TI  - A novel approach for the management of the chalkbrood disease infesting honeybee
      Apis mellifera L. (Hymenoptera: Apidae) colonies in Egypt.
AB  - Except for, very few articles regarding the influence of some organic acids on
      the causative pathogen, Ascosphaera apis Maassen, no other studies pertaining to
      the management of the chalkbrood disease were performed, so far in Egypt.
      Laboratory investigations indicated that the fungicides, i.e (Galben C 46%,
      Radomil gold pluse WP 42.5% and Daconil 2787) at their recommended rates did not
      exert any effect on the mycelical growth of the fungus. Therefore, these
      fungicides were completely excluded from the subsequent apiary trials. As to the
      Mycostatin, it was found clearly that this mycostatic compound was effective at
      the rates of 50.000 and 100.000 IU. Regarding the essential oils (ceder, clove,
      peppermint, parsley, black cumin, garden rocket, and ricin), ceder oil surpassed
      the other oils and materials in controlling the subject disease. It is peculiar
      that no studies on the efficacy of ceder are available in the literature, so the
      present work using ceder oil is recorded for the first time worldwide. Thymol
      substance at the rate of 2% showed also a great success in managing the CHB
      disease. Baised on the obtained results, the promising materials in controlling
      the disease could be arranged according to their efficacy in a descending order
      as follows: ceder oil>thymol>mycostatin and oxalic acid, so these highly
      effective materials were again tested under the apiary conditions. Outdoors
      (apiary) studies revealed that ceder oil 4% gave 100% reduction in mummies
      numbers. Reductions in number of fallen mummies ranged from 63.22 to 96.94, 18.93
      to 81.74, and 10.11 to 68.16%, on average, for thymol, mycostatin, and oxalic
      acid, respectively. From the practical point of view, thymol could be recommended
      for controlling the CHB disease, as it is the cheapest material and proved to
      increase the brood nest as well. In addition, thymol has other uses in the field
      of apiculture.

PMID- 16628895
TI  - Insect resistance in tomato accessions and their hybrid derivatives in Tamil
      Nadu, India.
AB  - Host plant resistance offers a viable alternative to the use of chemical
      insecticides for managing insects Infesting tomato. Hence, a study was carried
      out in Tamil Nadu, India during 1996 to 2004. An exhaustive germplasm comprising
      321 tomato accessions including cultivars, wild lines, land races, tribal/native
      tomatoes was gathered from various sources and screened for resistance against
      the major pest namely fruit worm, Helicoverpa armigera Hubner (Noctuidae:
      Lepidoptera). In the field screening, larval population and fruit damage was
      evaluated while in the glasshouse, foliage and fruit damage was assessed and ten
      promising accessions were selected. Based on further laboratory studies on the
      various mechanisms and bases of resistance, four accessions namely, Varushanadu
      Local, Seijima Jeisei, Ac 238 and Roma were selected and subjected to
      intercrossing by conventional hybridization, which yielded three viable hybrids.
      The resistance potentials of these hybrids against the fruit worm, H. armigera,
      leaf caterpillar, Spodoptera litura Fab. Noctuldae: Lepidoptera), leaf miner,
      Liriomyza trifolii Blanchard (Agromyzidae: Diptera) and whitefly, Bemisia tabaci
      Genn. (Aleyrodidae: Hemiptera) were probed both in the field and glasshouse along
      with their respective parents. The hybrids exerted lesser feeding and
      ovipositional preference and higher antibiotic effects on insect stages. The
      density of three types of non-glandular and two types of glandular trichomes and
      phenol content in the foliage, lycopene and ascorbic acid content in the fruits
      were the major factors of resistance. Based on these studies, Hybrid 3 (Ac 238 x
      Roma) and its derivatives were adjudged as potential accessions possessing insect
      tolerance.

PMID- 16628896
TI  - A promising biotechnical approach to pest management of Diabrotica virgifera
      virgifera in Illinois maize fields under kairomonal shielding with the new MSD
      technique.
AB  - Environmentally compatible and sustainable plant protection requires novel
      approaches to pest management characterized by minimal emphasis on toxicants.
      Classical toxicants traditionally dominated economic entomology for half a
      century. But worldwide problems with environmental pollution and with increasing
      resistance levels in all major pesticide classes and in many key insect species
      including Diabrotica virgifera virgifera (D.v.v.) strongly advocate a rethinking
      and a change in management paradigms used. Soft, minimally invasive, biological,
      biotechnical and cultural approaches should replace hard pesticides which are in
      favor up to now. Fortunately, pheromones, kairomones, plant attractants, better
      traps, new plant varieties and cultural methods like crop rotation, in short more
      sophisticated methods are now available as pressure for finding and exploring
      novel strategies increases. Facing this situation, a new biotechnical approach of
      population reduction of D.v.v., called "MSD" technique, is introduced. MSD is
      characterized as an approach combining mass trapping, shielding and deflecting of
      adult insects along an invisible odor barrier of synthetic kairomone which
      diminishes the flux of insects across a high capacity trap line baited with
      kairomone, thus reducing both the population fluctuation and number and its
      reproductive success within the shielded area. In the case of D.v.v. in Zea mays
      fields, effects realized by the MSD technique have been measured simultaneously
      by a number of independent criteria during the summers of 2003 and 2004 at 2
      different locations in Illinois maize fields of up to one half hectare size.
      Results observed are statistically significant and cannot be explained by mass
      trapping alone. There is also an additional shielding and deflection, in short
      "diversion" effect whose basic sensory and behavioral mechanisms call for future
      exploration.

PMID- 16628897
TI  - Possibilities to control the horse chestnut leaf miner (Cameraria ohridella) in
      urban environments.
AB  - The continuous epidemic infestation of horse chestnuts by C. ohridella is a
      serious aesthetic and economic problem in urban environments. The aim of the
      presented studies was therefore to develop control measures which meet the
      special needs of urban plant protection. Removal of infested leaves in autumn and
      appropriate disposal of the leaflitter is the only practicable measure to reduce
      infestation levels so far. Another two methods, which are currently in an
      experimental stage, had an impact on the leafminer populations. A gelformulated
      combination of the C. ohridella-pheromone with a contact insecticide as attract
      and-kill-system proved to be efficient at low population levels. Easily
      applicable and safe banks of systemic insecticides turned out to be effective in
      killing preimaginal stages of the leafminer on young trees. The complex of
      parasitoids attacking C. ohridella is comparable to that of other leafminers.
      Nevertheless, parasitism rates are very low at present and far away from having
      any controlling effect on the pest insect.

PMID- 16628898
TI  - Evaluation of transgenic approaches for controlling tuber moth in potatoes.
AB  - A wide spectrum of strategies to genetically engineer potato plants resistant to
      potato tuber moth, Phthorimaea operculella (Zeller), have been investigated. The
      potato cv Iwa was transformed with a range of genes under the transcriptional
      control of the CaMV 35S promoter using Agrobacterium-mediated gene transfer. The
      transferred genes encode protease inhibitors (spleen inhibitor and alpha1
      antitrypsin inhibitor), biotin-binding proteins (avidin and streptavidin) and Cry
      proteins (crylAc9, cry1Ba1, crylCa5 and cry9Aa2). Of these three transgenic
      approaches, cry genes have proved the most useful. In order to control the
      expression of the cry genes in foliage and not in the tubers a light-inducible
      Lhca3 promoter from potato was also used. The interaction of different cry genes
      was investigated using an experimental approach to simulate gene pyramiding in
      potato. Potato plants transgenic for both the crylAc9 and cryAa2 genes were
      developed and evaluated to help provide a more durable resistance to potato tuber
      moth.

PMID- 16628899
TI  - Evaluation of substituted oxime ethers for growth regulatory activity against
      Spodoptera litura (F.).
AB  - Insect growth regulatory activity (IGR) of fifty-two substituted oxime ethers
      were evaluated against an important polyphagous lepidopteran crop pest,
      Spodoptera litura (F.). A number of compounds produced symptoms comparable to
      exogenously applied juvenile hormone. Maximum IGR activity was exhibited by 4'
      (2,6,6-trimethyl-2-cyclohexen- -yl)-3'-buten-2'(E)-ketoxime-N-O-alkyl ether with
      an ED50 (morphological) of 40 microg g(-1) body weight, compared to 20 microg g(
      1) of JH III. Two more compounds namely 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'
      buten-2'(Z)-ketoxime-N-O-methyl propyl ether (ED50 192 microg g(-1)) and 4'
      (2,6,6-trimethyl-1-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether
      (ED50 380 microg g(-1)) showed considerable IGR activity, whereas 4'-(2,6,6
      trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentyl ether was found
      to be toxic to the larvae (ED50 268 microg g(-1)). Three compounds used in this
      study were also synergised by piperonyl butoxide (PBO). The synergistic ratios
      were found in the range of 1.33 to 4.605. The ovicidal activity of the oxime
      ethers is not significant.

PMID- 16628900
TI  - Identification of aphids attacking strawberries in Belgium.

PMID- 16628901
TI  - Comparative study on biological parameters of Bemisia tabaci (Genn.) collected on
      four host plants from Varamin-Iran.
AB  - During 2003 biological parameters of sweetpotato whitefly, B. tabaci (Genn.)
      (Horn. Aleyrodidae) as a major pest of field crops, vegetables and ornamentals
      were studied. In this study, the infested leaves of cucumber (Cucumis sativus L.)
      zucchini (Cucurbita pepo L.) eggplant (Solanum melongena L.) and cotton
      (Gossypium hirsutum L.) with whitefly nymphs and pupae were collected from
      Varamin-Iran, and were transferred to the laboratory. The newly emerged males and
      females of each population were released separately into a large cage set on
      cotton plants. Experiments were carried out in a growth chamber on cotton,
      (Varamin 76 variety) at 24+/-2 degrees C, 55+/-3% RH and 16:8 h (L: D)
      photoperiod. The adults of every collected population after emergency were reared
      in the large cages (40 x 50 x 70) containing pots of cotton plant. The
      preimaginal developmental time and reproductive parameters of 40 mated females
      were calculated for each population. The results revealed that the intrinsic
      rates of increase (r(m)), on cucumber, zucchini, eggplant and cotton were 0.093,
      0.068, 0.085 and 0.078 respectively, gross fertility rate, were 67.92, 59.08,
      76.13 and 63.14 respectively and mean generation time (T(c)) were 27.4, 27.74,
      27.73 and 27.52 days respectively. Other demographic parameters such as intrinsic
      birth rate (b), intrinsic death rate (d), finite rate of increase (lambda),
      doubling time (DT), net fecundity rate, net fertility rate , gross fecundity
      rate, mean age gross fecundity and fertility, mean age net fecundity and
      fertility, mean age hatch, number of eggs/female/day and daily reproductive rate
      were also calculated. The results revealed that there were not significant
      differences between parameters of demography in different populations and the
      host plant has no significant influence on biological parameters.

PMID- 16628902
TI  - Study of soybean leafhoppers fauna and an investigation on biology of dominant
      species Empoasca decipienspaoli in Karaj area.
AB  - The fauna of soybean leafhoppers and the biology of dominant species were
      investigated in Karaj during 1992-1994. For identification of species the male
      genitalia and other taxonomic characters were used. In order to find the duration
      and number of nymph stages, leaf cages were used on the plants. A thermograph was
      used to study the effect of temperature on nymphal stages in greenhouse. To study
      biology of E. decipiens in field four cages prepared and the trials has done
      inside them, and weekly all its life cycle observed. The following six species
      from four genera were identified: Empoasca decipiens Paoli, Macrosteles
      quadripunctulatus (KIrschbaum), M. laevis (Rib). Psammotettix alienus (Dahlbom),
      P. Striatus (Linne), Neoaliturus tenellus (Baker). Our investigations showed that
      Empoasca decipiens was the dominant species with the highest abundance. This
      specie is one of the important pests in many parts of Iran where oilseed crops
      are planted. The results showed that the soybean leafhopper over winters as adult
      under the debris of host plants and weeds. The first generation completes their
      life cycle on weeds before planting soybean. The second, third, and fourth
      generation lived on soybean. The time taken for the first, second, third, fourth
      and fifth nymphal stages were 6-7, 5-6, 2-4, 4-6 and 6-8 days, respectively.
      Adult longevity was 17-19 days, so that duration of first generation on weeds was
      54-66 days. Our experiments showed that, at 18 degrees C condition, the first
      stages have been the maximum nymph period and at 23 degrees C condition, have
      been the lowest period.

PMID- 16628903
TI  - The western corn rootworm diabrotica Virgifera virgifera en route to Germany.
AB  - The western corn rootworm Diabrotica virgifera virgifera LeConte
      (Col.:Chrysomelidae) (D.v.v.) is one of the most important maize pests in North
      America. Ever since its invasion into Europe and its detection near Belgrade
      airport by BACA in 1993 it quickly spread all over southeastern Europe and is now
      advancing towards central Europe. Up until summer 2004 considered free of D.v.v.,
      Germany is, with the exception of its northern and northeastern borders,
      surrounded by countries with proven D.v.v. infestations. In addition to
      simultaneous spot introductions by airplanes, three main routes for terrestrial
      introduction into Germany are likely: 1. from south to north via Lombardy (Italy)
      through Switzerland to the State of Baden-Wuerttemberg in the southwest; 2. from
      south east to northwest via Croatia, Slovenia, Austria into the State of Bavaria;
      and 3. from Belgium and the Netherlands in southeasterly direction to the state
      of Northrhine-Westfalia. From these, progress of D.v.v. along route 1 is so far
      the most advanced. It follows the well established network of road and rail
      connections through Switzerland and underscores the active role mankind and its
      technology plays as an active distribution vector for D.v.v. Mandatory crop
      rotation in the Swiss Canton of Ticino did slow down but could not prevent the
      northbound advance of D.v.v. in 2004. Considering the recent discovery of D.v.vu
      near the South German border, its introduction into German territory is only a
      matter of time and may be ecologically unavoidable. In Slovenla, another
      relatively small southern transit state, the D.v.v. population density is still
      much lower than in Switzerland but with significantly increasing trend during
      2004 and with special emphasis in its southeastern provinces. Considering its
      relatively short distance to southeastern Bavaria and the well developed
      transalpine rail, road and tunnel system, Slovenia as a transit state may provide
      another access route for D.v.v. of lesser but still significant importance to
      Germany.

PMID- 16628904
TI  - Monitoring presence and advance of the alien invasive western corn rootworm
      beetle in eastern Slovenia with highly sensitive Metcalf traps.
AB  - The American Chrysomelid beetle Diabrotica virgifera virgifera LeConte (D.v.v.),
      also called the western corn rootworm, spread from the location of its original
      introduction into Europe, Belgrade airport (BACA 1993), in all directions. Within
      a decade it occupied almost all countries of South-eastern and Central Europe.
      However, it reached Slovenia as late as 2003: Only 19 specimen were found in
      maize fields of the eastern and also western provinces. Already in the summer of
      2004, their number had risen to 386 which were mainly found in the eastern
      provinces near the borders to Croatia, Austria and Hungary. For their monitoring,
      a simple trap is being described which can be acquired in high numbers at a very
      low price and can guaranty a most sensitive detection of beetles. The Metcalf cup
      trap which in Slovenia so far has been unknown performed the task of monitoring
      quite well at five locations. It will also facilitate the future search for new
      and increasing infestations. Comparing 2004 with the year 2003, D.v.v. expanded
      its range in eastern Slovenia by about 15 km. These new infestations will include
      territories in which fields of the regionally Important oil seed pumpkin
      Cucurbita pepo are located. With important traffic connections between South
      eastern and Central Europe, Slovenia will occupy a bridgehead function in the
      preventive protection of maize from D.v.v. spreading into more northerly European
      regions including western Austria and southern Germany.

PMID- 16628905
TI  - Quick scouting of eggs of western corn rootworm (Diabrotica virgifera virgifera
      LeConte, 1868) from soil.
AB  - Main method to control the American Corn Rootworm is crop rotation (Camprag et.
      al., 1994) but we don't know how to determine the possible number of larvae under
      fall so we cannot use autumn cereals to change the row of cultivated plants. The
      pest spends almost 10 months in soil in egg and larval state (Chiang, 1973).
      There are two methods for scouting Diabrotica eggs and larval instars from soil
      over the winter. One of the two most important methods is holding soil samples on
      fixed temperature (Fromm et al., 1999). This method takes more than one and a
      half month but its result is highly reliable. The conventional egg-washing
      technique takes fewer days to count the number of Diabrotica eggs in soil but it
      has lower effectiveness than the other one because the eggs in a sample cannot be
      counted correctly. Our results show that the effectiveness of egg washing with
      high concentrated salty water (NaCl) is high and the method is quick enough to
      help planning the crop rotation even under the autumn period (Takacs et al.,
      2004).

PMID- 16628906
TI  - Comparison of leaf beetle assemblages of deciduous trees canopies in Hungary
      (Coleoptera: Chrysomelidae).
AB  - The species richness and species composition of Coleoptera assemblages were
      investigated in deciduous tree canopies in Hungary. Apple and pear orchards were
      investigated in Nagykovacsi, Kecskemet and Sarospatak in 1990-94, and limes and
      maples in Keszthely in 1999-2002. Faunistic results and conclusions of these
      investigations were published elsewhere. Examination of the fauna of parks,
      avenues and other planted urban plant stocks has only begun to occupy researchers
      in the last decade in Hungary. The proportion of leaf-beetle species in the
      material gathered on maples and limes ranged between 17.0 and 21.3 per cent. The
      commonest leaf-beetle specimens collected in the lime canopy were Aphthona
      euphorbiae, Chaetocnema tibialis, Longitarsus lycopi, L. pellucidus, L. pratensis
      and L. succineus. The commonest on maple were Aphthona euphorbiae, Chaetocnema
      concinna, C. tibialis, Longitarsus lycopi, L. pellucidus, L. succineus,
      Phyllotreta cruciferae and P. vittula. This study presents the details on the
      composition of the chrysomelid communities that was compared by metric ordination
      using the Syntax 5.1 program.

PMID- 16628907
TI  - Assessment of losses in honey yield due to the chalkbrood disease, with reference
      to the determination of its economic injury levels in Egypt.
AB  - In Egypt, the chalk brood (CHB) disease caused by the fungus, Ascosphaera apis
      Maassen started again infesting the honeybee, Apis melifera L (Hymenoptera:
      Apidae) colonies after a cessation pause of seven to nine years. For the first
      time, an attempt has been made to look into the problem of the CHB disease from
      the view point of assessing losses in both clover (Trifolium alexandrinum) and
      chinus (Chinus molus) honey yields. In this regard, two techniques were adopted.
      Under the natural conditions of the experimental apiary (first technique), loss
      in clover honey was 18.412 +/- 0.663%, on average, whereas the average loss in
      chinus honey was 18.332 +/- 1.536%. In the second technique of loss appraisal
      (artificial infection). The tested honeybee colonies were artificially infected
      with four sources of A. apis infection, I.e. black mummies, white mummies, pollen
      grains and water, in addition to controls to create the so-called "different
      levels of infection". The mean percentages of losses in clover honey were 30.06
      +/- 1.807, 27.95 +/- 1.062; 21.13 +/- 0.987; 16.96 +/- 0.672 and 0.00 +/- 0.00
      for black mummies, white mummies, pollen grains, water and control, respectively.
      Taking into account the relationship between number of resulted mummies in each
      source of infection and % loss in clover honey, it could be concluded that as the
      resulted mummies increased, the corresponding clover honey yield decreased in
      each source of infection. It was noticed that the % loss in clover honey differed
      as the used technique differed. For example, the percentage loss in clover honey
      produced from colonies exposed to the natural conditions was relatively less than
      that of the artificially infected ones. This has been discussed in the text.
      However, the causative pathogen of CHB disease resulted in serious decrease in
      honey production. Loss appraisal is a perquisite step for the determination of
      the economic injury levels (EILs). By regressing % loss in clover honey yield
      against the total number of fallen mummies, the linear equation was worked out to
      be: Y = 0.242 + 0.040 x (r2 = 0.99, F = 62408.865). Depending on the total costs
      of controlling CHB disease, the EIL values were 31.875 and 11.250 mummies/colony
      for cedar oil and thymol granules, subsequently. As to the chinus honey the
      corresponding EILs were 18.940 and 6.683 mummies/colony for cedar oil and thymol
      granules, in respect, as a result of adopting the regression formula: Y = -6.762
      + 0.101 X. As for the clover honey (artificial infection) the EIL values were
      39.844 and 14.063 mummies/ colony in case of using cedar oil and thymol grains,
      subsequently. These values were worked out using the formula Y = 5.871 + 0.032 X.
      From the practical point of view, apiarists should not use thymol or cedar oil as
      fallen mummies don't reach the suggested EILs values to minimize control costs as
      much as possible.

PMID- 16628908
TI  - Seasonal coincidence between rosy apple aphid fundatrices and their parasitoids:
      implications for an early biological control of Dysaphis plantaginea.
AB  - The potential contribution of the aphid parasitoid Ephedrus persicae Froggatt
      (Hymenoptera: Braconidae, Aphidiinae) in regulating stem mothers of the rosy
      apple aphid Dysaphis plantaginea (Passerini) (Homoptera: Aphididae) was
      investigated in culture conditions using both species' phenological emergence
      data in spring and host stage suitability trials. In 2003, emergence of E.
      persicae started on April 1st, i.e., 108.2 degree-days (base: 4.5 degrees C;
      start date: January 1st) later than its host on March 10th. When less than 3% of
      parasitoids had emerged on April 12th, more than 97% of D. plantaginea stem
      mothers had moulted beyond their 1st instar. The latest parasitoids left their
      diapause mummies in late April as the majority of fundatrices had reached the
      adult stage. Parasitisation trials demonstrated the suitability for E. persicae
      of all developmental stages of rosy apple aphid fundatrices, including mature
      individuals. No offspring were deposited by fundatrices parasitised as Ist-instar
      nymphs but later instars did produce a progeny whose size was substantially
      reduced compared with unparasitised individuals, and scaled against their age at
      the time of parasitisation. Although the temperature accumulation required for
      emergence in spring is reached later for E. persicae than for its host aphids,
      thus allowing part of the stem mother population to temporarily escape
      parasitisation and reach maturity, the marked reduction in fecundity of
      individuals parasitised even as late-instar nymphs does confer to E. persicae a
      non-negligible role in potentially regulating D. plantaginea.

PMID- 16628909
TI  - Internal labelling of the eggs of the aphidophagous hoverfly Episyrphus balteatus
      (De Geer) (Diptera: Syrphidae) with a fluorescent dye.
AB  - A method was developed to label the egg load of Episyrphus balteatus (De Geer)
      (Diptera: Syrphidae) by feeding adult females with the fluorescent dye Rhodamine
      B. In a preliminary experiment aimed at selecting an appropriate dye
      concentration, gravid females reared in insectary conditions were provided for
      two successive days with a 50% honey-water solution enriched with Rhodamine B at
      concentrations of 0.1%, 0.01% and 0.001%. Eggs deposited on aphid-infested broad
      bean plants by syrphid females fed with Rhodamine B 0.01% showed the most intense
      marking. The higher dye concentration induced irregular marking among the eggs,
      presumably due to its repellent taste and consequently lower intake by the flies.
      A second series of trials focused on the persistence of the marker, prior and
      after oviposition, at the selected (optimal) dilution. A reduction in the marking
      degree of eggs was observed when the first egg deposition was delayed for one day
      after removing the dye from the cage. When marked females were allowed to deposit
      further batches of eggs the subsequent days, fewer eggs were laid and their
      fluorescence properties was reduced. Exposure to direct sunlight during 10 hours
      had no detectable effect on the fluorescence level of marked eggs deposited on a
      bean plant. The egg-marking technique examined in this study could be useful to
      determine the crop area accommodating eggs deposited by marked syrphid females
      migrating from a release point into cultivated fields.

PMID- 16628910
TI  - Postharvest heat and cold treatment to control Ceratitis capitata on cactus pear
      fruit.
AB  - In order to work out a quarantine treatment for cactus pear fruit a factorial
      experimental plan was carried combining postharvest water dips at 20, 50, 54, 58
      and 60 degrees C and storage at 1 degrees C for 3, 6 and 10 days. Cactus pear
      fruit cv 'Rossa' were artificially infested with Med. fly eggs (at least 20 eggs
      per fruit) then left in the lab at 25 degrees C for 4 days. Treatments took place
      by dipping the fruit at each water temperature for 2 mm. At each established time
      fruit was picked and checked for vital larvae and degree of chilling injury (CI).
      Probit 9 requirements were achieved in all cases when fruit was cold-stored for
      10 days. When fruit was kept for 6 days the quarantine requirement was achieved
      only by dipping the fruit at 58 and 60 degrees C while none dip treatment was
      effective if fruit was stored for 3 days at 1 degrees C. All Fruit stored for 10
      days at 1 degrees C showed severe CI symptoms and when kept for 6 days the same
      degree of CI was found on fruit dipped in water at 20, 58 and 60 degrees C. No CI
      was observed after 3 days at 1 degrees C. In conclusion only when fruit was
      dipped at 50-54 degrees C and stored for 10 days at 1 degrees C the probit 9
      condition was attained with acceptable CI symptoms.

PMID- 16628911
TI  - Biological control of Aphis gossypii on pepper plant using Coccinella algerica.
AB  - To calibrate biological control in pepper plant against Aphis gossypii using
      Coccinella algerica different experimentation were made. The consumption of C.
      algerica during the larval stage was enumerated in laboratory conditions. The
      densities (1, 4, 8 larvae/plant) to L2 stage of C. algerica necessarily to
      decrease aphid's populations were determined in plant pepper and the daily
      consumption in the pepper plant at the different densities was calculated. The
      density with 8 larvae at semi natural conditions is higher significantly. In
      protected crop of pepper, different releases to C. algerica were made with eggs,
      second stage larva and with ladybird before infestation with A. gossypii. A
      strategy to introduce L2 stage is preferred than the release with punters of C.
      algerica at different densities. At the same, the Introduce L2 stage is compared
      to release the C. algerica ladybird before the infestation of A. gossypii in the
      protected crops. The activity of ladybird has been maintained in the protected
      crop and it was shown when the infestation appeared.

PMID- 16628912
TI  - The effect of predators and hymenopterous parasites on population fluctuations of
      alfalfa aphids.
AB  - Among alfalfa pests in Iran three aphid species, green alfalfa aphid
      Acyrthosiphon pisum Harris spotted alfalfa aphid Therioaphis trifolii forma
      maculata Buckton and blue alfalfa aphid, Acyrthosiphon kondoi Shinji are
      important pests. The green alfalfa aphid can be observed all along the growing
      season particularly from late May to mid June at Karaj climate conditions. During
      this period, the mean monthly maximum temperature and relative humidity were
      about 28 degrees C and 60-65% respectively. This aphid overwinters as nymph and
      viviparous female. Sexual forms and eggs could not be seen under field
      conditions. Spotted alfalfa aphid, Therioaphis trifolii fonna maculata is the
      most prevalent aphid in summer time, when the mean monthly maximum temperature
      and relative humidity are about 33-34 degrees C and 44-58% respectively. Sexual
      individuals have been observed in the laboratory but not in the field. Among
      predators (Coccinella septempunctata, Adonia variegata, Syrphus cinctus, S.
      corolae, S. grassulariae, Chrysoperla carnea and Nabis capsiformis) one
      coccinellid species, C. septempunctata, had greatest impact on fluctuations of
      population. Among hymenopterous parasitoids two species have been collected from
      alfalfa field they were Aphidius ervi and Praon palitans. These parasitoids
      destroyed a good percent of aphids and statistically proved to lower aphid
      populations significantly.

PMID- 16628913
TI  - Population dynamics of banded thrips (Aeolothrips intermedius Bagnall,
      Thysanoptera, Aeolothripidae) and its potential prey Thysanoptera species on
      white clover.
AB  - In 2002, the occurrence of banded thrips (Aeolothrips intermedius Bagnall) and
      some other Thysanoptera species on white clover (Trifolium repens L.) was
      monitored at two locations in the continental part of Slovenia. White clover
      presents in many countries important intercrop in integrated vegetable
      production. Light blue sticky boards were placed on grasslands (one parcel on
      each location) with high percentage of white clover. Sticky boards were changed
      in about 10-days intervals from the end of April till the beginning of October.
      Number of caught individuals on the boards was counted. They were classified in
      three different groups: 1. Aeolothrips intermedius, 2. representatives of
      Haplothrips, Odontothrips and Frankliniella genera, 3. representatives of Thrips
      genus. We stated that, compared with the other Thysanoptera species in the open,
      predatory thrips occurs in lower number. Predatory species Aeolothrips
      intermedius was the most numerous during the flowering of white clover. It was
      established that other Thysanoptera species (the most of them are facultative
      phytophagous species) were more numerous also in the periods of less favourable
      weather conditions and during the non-flowering growing stages of white clover.
      Based on the results of present research we concluded that A. intermedius has a
      potential to control onion thrips (Thrips tabaci Lindeman), especially in July
      and August, when in the open both species occur in high numbers.

PMID- 16628914
TI  - Efficacy of some insecticides against the small red belted clearwing borer,
      Synanthedon myopaeformis (Borkh.) (Lepidoptera: Sessiidae), in apple orchards in
      Jordan.
AB  - Experiments were carried out in Ash-Shoubak on 10-year old apple trees, Malus
      domestica cv. Mondial Gala grafted on M26 that were infested with the small red
      belted clear wing moth. The efficacy of five insecticides was tested against this
      insect by either spraying or injecting the infested trees. The tested
      insecticides were; Comodor (imidaclorpid), Chlormezyl (chlorpyrifos &
      dimethoate), Avaunt (indoxacarb), Thvap (cyromazine) and Actellic (pyrimiphos
      methyl). All of these insecticides were applied in 2003 and 2004 except that of
      Actellic that was applied only in 2004. Data on larval mortality have been
      observed after 2, 7 and 14 days of insecticides applications. Results showed that
      spraying or injecting Chlormezyl or Actellic resulted in a significant overall
      efficacy against the larvae of S. myopaeformis. It was also observed that
      injecting Comodor improved its overall efficacy against the insect.

PMID- 16628915
TI  - Comparative toxicity of three ecdysone agonist insecticides against the
      Mediterranean flour moth.
AB  - The Mediterranean flour moth, Ephestia Kuehniella Zeller (Lepidoptera:
      Pyralidae), is an important pest in stored products worldwide, and is one of the
      major pests in flour mills in Algeria. Because environmental consideration,
      alternative approaches to neurotoxic insecticides, as well as safe, effective,
      and sound integrated pest management strategies are developed pest control agents
      such as the insect growth regulator (IGRs). Among these IGRs, the
      bisacylhydrazine derivatives are nonsteroidal ecdysterold agonists that mimic the
      action of moulting hormones and induce a precocious and incomplete moult in
      several insect orders. In topical bioassays using the pupae of E. kuehniella,
      three ecdysteroid agonists: RH-5849, the first bisaclhydrazine ecdysone agonist
      and two analogs, RH-5992 (tebufenozide) and RH-0345 (halofenozide), were
      evaluated on the reproduction under laboratory conditions. In a first series of
      experiments, the efficacy of these compounds was tested. These compounds
      exhibited insecticidal activity and the duration of pupal development was reduced
      with a dose-response relationship. Among the three tested compounds, tebufenozide
      (LD50 = 0.005 microg) appeared the most potent ecdysteroid agonist against E.
      kuehniella (RH-5849: LD50 = 0.05 microg and RH-0345: LD50 = 5.10 microg). In a
      second series of experiments, the effects of the ecdysone agonists (LD50) were
      investigated on the reproduction. Data showed that the three compounds affected
      growth of ovaries as evidenced by morphometric measurements of the ovaries from
      newly emerged adult females. In addition, the thickness of the chorion from basal
      oocytes was reduced only by RH-5992 and RH-0345. However, electron microscopic
      observations revealed that the three compounds had no significant effect on the
      fine structure of chorion. Finally, measurements of ovarian ecdysteroids'
      production by an enzyme immunoassay showed an increase in the hormonal amounts
      recorded in treated series compared to control series.

PMID- 16628916
TI  - Toxicity of fenitrothion, an organophosphorus pesticide, against summer
      population of sunn pest, Eurygaster integriceps Put. (Hemiptera: Scutelleridae).
AB  - The sunn pest are a group of insect representing several genera of the shield bug
      (Scutelleridae) and stink bug (Pentatomidae) families, with the species
      Eurygaster integriceps being the most economically important. The sunn pest is a
      major pest of wheat and barley in central and western Asia and it accounts for
      annual losses of 20-30% for barley and up to 100% for wheat. In the recent
      decades problems have intensified largely due to change in farming practices.
      Thus this pest threatens food security and reduces the stability of traditionally
      wheat-based agricultural systems. In order to control pest, the major
      organophosphorus insecticide used is fenitrothion. So, the aim of the current
      study was to determine toxicity of fenitrothion against summer population of
      adult sunn pest. Insecticide toxicity was measured using a topical bioassay. To
      do so, the toxin was dissolved in acetone and six concentrations of toxin
      including 25, 50, 100, 150, 175 and 200 ppm were prepared. Insects were treated
      on the pronotum with one micro litre aliquots of insecticide in acetone (for
      treatments) or acetone alone (for control). The dose-mortality relationship was
      assessed from above mentioned doses with 30 insects treated per dose. After
      treatment, insects were maintained at laboratory conditions and mortality was
      recorded after 48 hours. Results were corrected for control mortality with
      Abbott's formula and then analyzed and toxicity determined. The obtained results
      showed that LD10, LD50, and LD90 were 34.7, 90.43, and 235.5, respectively.

PMID- 16628917
TI  - Sublethal effects of imidacloprid and pymetrozine on the life table parameters of
      Aphis gossypii Glover (Homoptera: Aphididae).
AB  - In this study we report the sublethal effects of recommended concentrations of
      imidacloprid and pymetrozine on cotton aphid's reproduction. Fecundity life table
      parameters for AG were studied on cucumber under conditions of 25+/-1 degrees C,
      70+/-5% RH and photoperiod of 16:8 (L:D). Leaf discs of cucumber immersed in the
      recommended concentrations of the above mentioned insecticides and controls and
      the new born female was released on the lower surface of leaf discs. Values of
      parameters such as adult longevity and daily fecundity rate were recorded.
      Standard error of population growth parameter was calculated using the Jacknife
      method. The results show that these two insecticides significantly reduce life
      table parameters compared with control.

PMID- 16628918
TI  - Potential use of essential oils from Cameroon applied as fumigant or contact
      insecticides against Sitophilus zeamais Motsch. (Coleoptera: Curculionidae).
AB  - Essential oils from seven plants species currently found in Cameroon were
      extracted by steam distillation and tested for their insecticidal activities
      against Sitophilus zeamats Motsch. Responses varied with the test applied and the
      plant species. For the contact toxicity, the acetone was used in order to dilute
      the pure essential oil. Formulations of 1% of essential oils of Xylopia
      aethiopica and Ocimum gratissimum were the most toxic and led to 96 and 98% of
      mortality respectively after 24 h. There was no death in control (0% of
      mortality). Fumigation test were done by applying 300 microl of pure essential
      oils in the bottom of closed 800 ml glass containers. In that case, the essential
      oil of Hyptis spicigera was the most toxic (fumigant) after 48 hours of
      fumigation followed by Annona seregalensis and Xylopia aethiopica 96 and 95% of
      mortality respectively. Some of the essential oils of plant species tested are
      promising for pest control in farmer granaries. However, further investigations
      are to be done on formulation and side effects.

PMID- 16628919
TI  - Bio-insecticidal activities of halophytic plant extracts against Tribolium
      confusum (Coleoptera, Tenebrionidae).
AB  - Salt marsh plants were tested for their insecticidal activities against larvae of
      the confused flour beetle Tribolium confusum (Tenebrionidae). 16 aerial part
      extracts were obtained using organic solvents of increasing polarity and tested
      for their anti-feedant and toxicity effects. Responses varied with plant material
      and extract type. Ethyl acetate extracts of F. laevis, S. echioides and. T.
      boveana and petroleum ether extract of F. laevis presented, anti-feedant
      property. However, S. fructicosa seemed to be attractive to the tested flour
      beetle. Mortalities of 97, 87, 97 and 80% were observed by using respectively
      ethyl acetate extracts of F. laevis, S. echioides and T. boveana and petroleum
      ether extract of F. laevis, when applied at a dose of 1%, mixed with the insect
      diet. This preliminary study showed that F. laevis, S. echioides and T. boveana
      presented potential bio-insecticidal activity with ethyl acetate extracts,
      similar result was found with petroleum ether extract of F. laevis. More
      complementary studies are needed for the use of these extracts to control T.
      confusum.

PMID- 16628920
TI  - Bioactivities of seven chrysanthemum species flowers powder on Spodoptera
      littoralis (Boiduval) larvae.
AB  - We have screened seven Chrysanthemum species, collected from different biotope in
      Tunisia for the antifeeding and growth regulatory activity against S. littoralis
      (Lepidoptera: Noctuidae) an insect pest of tomato. The flowers powder was added
      to the Poitout and Bues (1974) artificial diet at three concentrations: 4, 8, and
      16%. After ten days of treatment, the consumed quantity determination revelled
      that these species have an antifeeding activity proportional to the
      concentration, more considerable for the C. fuscatum and C. Myconis flowers
      powder. At the concentration of 16% the larvae weight was significantly delayed
      in the average time to the control, these results were compared to the effect of
      Cestrum parquii on S. littoralis and Pieris brassicae The moulting date
      determination showed an elongation of the third, fourth and fifth stages at the
      high concentration probably due to the presence of juvenile hormones Analogues.

PMID- 16628921
TI  - Experiments for studying the molluscicidal potential of Cestrum Parqui
      (Solanaceae) saponins against Theba pisana (Helicidae) snails.

PMID- 16628922
TI  - Insecticidal and growth inhibitory effects of new O-acyl chitosan derivatives on
      the cotton leafworm Spodoptera littoralis.

PMID- 16628923
TI  - Insecticidal and growth inhibition effects of chitosan derivatives containing an
      N-alkyl group on the cotton leafworm Spodoptera littoralis.

PMID- 16628924
TI  - The influence of methyl jasmonate (JA-Me) and B-glucosidase on induction of
      resistance mechanisms of strawberry against two-spotted spider mite (Tetranychus
      urticae Koch.).
AB  - The goal of the research was to study the influence of methyl jasmonate (JA-Me)
      and beta-glucosidase treatments on fecundity and preference to infestation and
      oviposition of two-spotted spider mite feeding on strawberry. The experiments
      were conducted in laboratory conditions on leaves of Aga and Kent cultivars.
      Leaves were treated with: a. solution of 0.1% JA-Me in 0.05% Triton X-100 (by
      spraying); b. beta-glucosidase dissolved in 0.1 M citrate buffer at pH 6 (by
      petiole); c. 0.05% solution of the Triton X-100 (by spraying); d. 0.1 M citrate
      buffer at pH 6 (by petiole). In the no-choice test, application of JA-Me on
      leaves of strawberry caused reducing of number of eggs laid during three days of
      the experiment. In the choice test, which was carried out for determination of
      non-preference mechanism of resistance, there was a statistically significant
      lower number of mites on leaves treated with JA-Me compared to leaves treated
      with other compounds as well as to non-treated leaves after 24 hours from
      solutions application. Moreover, at the same experiment, females of two-spotted
      spider mite laid the least number of eggs on leaves treated with JA-Me. Analysis
      conducted using liquid chromatography method, revealed increase of the level of
      phenolic compounds like chlorogenic acid and rutin on leaves treated with JA-Me.
      Thus, it appears that JA-Me may be involved in antybiosis or non-preference
      mechanisms of resistance of strawberry to two-spotted spider mite.

PMID- 16628925
TI  - Activity of kk-42 in combinated treatment with RH-0345 or 20-hydroxyecdysone on
      morphometric measurements and free ecdysteroid in eggs of mealworms.
AB  - RH-0345 (halofenozide), a bisacylhydrazine derivative, is a nonsteroidal
      ecdysteroid agonist that mimics the action of the moulting hormones, while KK-42,
      an imidazole compound, is a potent inhibitor of ecdysteroid biosynthesis. Recent
      experiments with Tenebrio molitor suggested that the reduction of ecdysteroid
      titer, leading to a reduction of reproductive capacity, is due to a direct and
      rapid action of KK-42 on ecdysterold biosynthesis. Moreover, RH-0345 could partly
      restore the effects on reproductive events induced by KK-42. On the other hand,
      RH-0345 was found to affect growth and development of ovaries in a manner similar
      to that 20-hydroxyecdysone (20-E) and increased the ecdysteroid production.
      Therefore, the present study evaluates KK-42 applied topically (10 microg/insect)
      in combination with RH-0345 or 20-E in order to obtain more information on the
      mode of action of this compound on reproduction in T. molitor. In a first series
      of experiments, the compounds were assayed on morphometric measurements of
      freshly laid eggs. Results showed that both the weight and the volume of eggs
      increase significantly in series treated by KK-42 followed by 20-hydroxyecdysone
      as compared to controls and treated series by KK-42 followed by RH-0345. Data
      from enzyme immunoassay measurements revealed that KK-42 applied before 20-E was
      found to reduce significantly the amounts of free ecdysteroids in eggs
      comparatively to the others series.

PMID- 16628926
TI  - Effects of a neonicotinoid insecticide (acetamiprid) on acetylcholinesterase
      activity and cuticular hydrocarbons profil in German cockroaches.
AB  - Acetamiprid was incorporated into the diet at 2% dose corresponding to the LD50
      and orally administrated to newly emerged adults of the German cockroach
      Blattella germanica and investigated on acetylcholinesterase activity and
      cuticular hydrocarbons profil. Acetylcholinesterase specific activity was
      determined on adult males and females after 24, 48 and 72 hours of treatment.
      Pentanic extracts of cuticular hydrocarbons in males and females after 6 days of
      treatment were analysed by gas chromatography. Data revealed an increase in
      acetylcholinesterase activity in both sexes from the control series. However, a
      significant inhibition in AChE was observed after treatment at 24, 48 and 72
      hours especially in females. In addition, hydrocarbons profils were found
      qualitatively similar in all groups of insects. However, slight quantitative
      differences between sexes in control series were noted. Acetamiprid feminize the
      cuticular profil in males with significant reduction of cuticular compound, and
      these allowed separation of insects into two groups using multivariate analysis.

PMID- 16628927
TI  - Effect of JH III and substituted oxime ethers on the in vitro protein and RNA
      synthesis in male accessory reproductive gland (MARG) of Spodoptera litura (F.).
AB  - The physiological action of two substituted oxime ethers namely: 4'-(2,6,6
      trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-propylether (compound
      No. 3) and 4'-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O
      pentylether (compound No. 34,) were compared with that of JH III in an in vitro
      assay to monitor the synthesis of RNA and protein in male accessory reproductive
      gland (MARG) of Spodoptera litura by using 3H-leucine and 3H-uridine,
      respectively. Both the compounds have stimulated protein synthesis compare to
      control. Compound No 34 is slightly more effective than JH III in increasing the
      protein synthesis at physiological concentration of 10(-6) and 10(-5) M. Compound
      No 3 and JH III have doubled the RNA synthesis and increased the protein
      synthesis by 1.5 times over the control at 10(-4) to 10(-6) M concentrations.
      While JH III at 10(-5) M significantly enhanced RNA synthesis, similar effect is
      produced only at 10(-3) M by compound No 3 and 34.

PMID- 16628928
TI  - Protein profiles of Spodoptera litura (F.) male accessory reproductive gland and
      its secretions.
AB  - Protein profiles of the male accessory reproductive glands of a polyphagous pest,
      Spodoptera litura (Lepidoptera: Noctuidae) and their glandular secretions were
      analyzed by electrophoresis under denaturing conditions. The study revealed the
      presence of 23 proteins in the glands and 14 in the secretions. The molecular
      weights of the gland proteins ranged from 163 to 3.8 KD whereas that of
      secretions ranged from 100 to 3.8 KD. The 9 low molecular weight proteins of the
      secretions are a characteristic feature. It is suggested that the secretions may
      contain a sex peptide that has a role in the fertility and fecundity of the
      females.

PMID- 16628929
TI  - A amylase activity of nymphal stages of sunn pest, Eurygaster integriceps Puton
      (Hemiptera: Scutelleridae).
AB  - Wheat production in Iran has changed substantially over the past one or two
      decades with development of higher-yielding cultivars and improved methods of
      planting. Sunn pest, Eurygaster integriceps (Heteroptera: Pentatomidae), is the
      most important cereal pest in Iran. Sunn pest like other insect pests of wheat
      lives on a polysaccharide-rich diet and depends to a large extent on
      effectiveness of their alpha-amylases for survival. alpha-amylase (1-4-alpha-D
      glucan glucanohydrolase) hydrolyses starch, and related polysaccharides by
      randomly cleaving internal alpha-1,4-glucosidic linkages and has a major role in
      the utilization of polysaccharides. The recent increase in study of insect
      digestive enzymes seems to make sense in the realization that the gut is the
      major interface between the insect and its environment. Hence, an understanding
      of digestive enzyme function is essential when developing methods of insect
      control such as the use of enzyme inhibitor's and transgenic plants to control
      phytophagous insects. The aim of the current study is to identify and
      characterize alpha-amylase activity in order to gain a better understanding of
      its digestive physiology, which hopefully will lead to new strategies of the
      insect control. In order to analyze a-amylase activity adult and different
      nymphal stages were collected from wheat field from Karaj area and midgut complex
      from these individuals were dissected under a light microscope in ice-cold saline
      buffer (0.006M NaCl). After homogenization in buffer, homogenate was centrifuged
      at 15000 g for 20 min at 4 degrees C. The supernatant was pooled and stored at 
      20 degrees C for subsequent analysis. alpha-amylase activity was assayed by the
      dinitrosalicylic acid (DNS) procedure using soluble starch as substrate (starch
      1%). Our result showed that enzyme activities in different nymphal stages (first,
      second, third, fourth and fifth stadium) were 0.19, 0.78, 1.21, 1.23, 1.25
      units/mg protein, respectively.

PMID- 16628930
TI  - Effect of plant a-amylase inhibitors on sunn pest, Eurygaster integriceps Puton
      (Hemiptera: Scutelleridae), alpha-amylase activity.
AB  - Plant-insect interaction is a dynamic system, subjected to continual variation
      and change. In order to reduce insect attack, plants developed different defence
      mechanisms including chemical and physical barriers such as the induction of
      defensive proteins, volatiles that attract predators of the insect herbivores and
      secondary metabolites. Proteinaceous inhibitors of alpha-amylase and proteases
      are widely distributed in cereals, legumes and some other plants. Because of the
      possible importance of these inhibitors in plant physiology and animal nutrition,
      extensive research has been conducted on their properties and biological effects.
      Sunn pest like other insect pests of wheat lives on a polysaccharide-rich diet
      and depends to a large extent on effectiveness of their alpha-amylases for
      survival, a-amylase (1-4-alpha-D-glucan glucanohydrolase) hydrolyses starch, and
      related polysaccharides by randomly cleaving internal alpha-1,4-glucosidic
      linkages and has a major role in the utilization of polysaccharides. The enzyme
      inhibitors act on key insect gut digestive hydrolyses, alpha-amylase. Several
      kinds of a-amylase inhibitors present in seeds and vegetative organs of plant,
      act to regulate number of phytophagous insects. Therefore, the aim of the current
      study is to study cereal proteinaceous inhibitors of insect digestive enzymes and
      their potential use as resistance factors against Sunn pest. The proteinaceous
      inhibitors from different cereal species including barley (Hordeum vulgare L.)
      and wheat (Triticum aestivum L.) were extracted and tested in in vitro condition
      against Sunn pest alpha-amylase. Extraction was made with NaCl (0.15 M) at room
      temperature and further purification was done by ammonium sulphate precipitation.
      It was found that fractions obtained from barley had more inhibitory effect on
      amylase activity of Sunn pest than fractions obtained from wheat. Knowledge
      gained through these studies can be used to select resistant plant against insect
      pest.

PMID- 16628931
TI  - Esterase activity in summer population of sunn pest, Eurygaster integriceps Put.
      (Hemiptera: Scutelleridae).
AB  - A key constraint on increasing wheat production in Iran and some neighbouring
      countries is Sunn pest which cause severe damage to vegetative growth stage of
      plant in the early season. It also feeds on wheat grain in late growth stage of
      plants thus damaged wheat grains loose their bakery properties. Because of
      injecting protease enzymes into the grain during feeding, enzymes degrade gluten
      proteins and cause rapid relaxation of dough which results in the production of
      bread with poor volume and texture. Organophosphorus insecticides are the main
      pesticides used to control the insect pest. However, suitable reduction in pest
      population has not been achieved partly due to resistance to pesticides. Esterase
      plays crucial roles in insect physiology and detoxifies a broad range of
      xenobiotics including insecticides. Enhanced esterase activity is a major
      mechanism if insecticide resistance and has been detected in a number of insects.
      To evaluate esterase activity adult bugs were collected from wheat field in Karaj
      area of Iran and transferred to the laboratory. For biochemical assay, two adult
      bugs (either males or females) were homogenized in 500 microl Na-phosphate buffer
      pH 7.2. The homogenates were centrifuged at 14000 g for 10 minutes at 4 degrees
      C. The supernatants as the enzyme source were pooled and stored at -20 degrees C
      for later use. For enzyme assay, 300 microl of supernatant was mixed with equal
      volume of substrates (30 mM alpha-naphthyl acetate or 30 mM beta-naphthyl
      acetate) and incubated at 30 degrees C for 30 minutes. Then, 50 microl of fast
      blue solution (150 mg fast blue B in 15 ml distilled water plus 35 ml 5% SDS) was
      added and esterase activity was determined in a spectrophotometer at 595 nm. Data
      showed that there are no differences in esterase activity between male and
      female. However, There was significant differences between hydrolysis of
      substrates, alpha-naphthyl acetate and beta-naphthyl acetate. Insect esterase
      hydrolyzes alpha-naphthyl acetate much more than beta-naphthyl acetate.

PMID- 16628932
TI  - Digestive proteinase activity of the Khapra beetle, Trogoderma granarium Everts
      (Coleoptera: Dermestidae).
AB  - The khapra beetle, Trogoderma granarium, is one of the most important stored
      product pests worldwide. A study of digestive proteinases in T. granarium was
      performed to identify potential targets for proteinaceous biopesticides, such as
      proteinase inhibitors. The pH of guts was determined by addition of pH indicator
      solutions to broken open gut regions. The last instar larvae were dissected in
      cold distilled water and the whole guts were cleaned from adhering unwanted
      tissues. The pooled gut homogenates were centrifuged and the supernatants were
      used in the subsequent enzyme assay. Total proteinases activity of the gut
      homogenates was determined using the protein substrate azocasein. Optimal
      azocasein hydrolysis by luminal proteinases of the larvae of T. granarium was
      highly alkaline in pH 10-10.5, although the pH of luminal contents was slightly
      acidic (pH 6.5). The extract showed the highest activity at 55 degrees C (pH
      6.5), 45 degrees C (pH 8) and 30 degrees C (pH 10). The proteolytic activity was
      strongly inhibited in the presence of phenylmethylsulphonyl fluoride (82.33+/
      4.37% inhibition). This inhibition was decreased with increasing of the pH of
      assay incubating medium. N-p-tosyl-L-lysine chloromethyl ketone (51.6+/-3.3%
      inhibition) and N-tosyl-L-phenylalanine chloromethyl ketone (27.23+/-4.37 %
      inhibition) showed inhibitory effect on proteolysis. Addition of thiol activators
      dithiothreitol and L-cysteine had not enhanced azocaseinolytic activity. The data
      suggest that protein digestion in the larvae of T. granarium is primarily
      dependent on serine proteinases; trypsin- and chymotrypsin-like proteinases.

PMID- 16628933
TI  - Meloidogyne minor: a threat to temperate crops?

PMID- 16628934
TI  - A study about geographical distribution of root lesion nematode (Pratylenchus
      loosi, Loof 1960) in tea gardens at Guilan Province, Iran.
AB  - Root lesion nematode of tea (Pratylenchus loosi) is one of the most dangerous and
      distractive pests in all over areas in the world where tea grows. In Iran, this
      species was one of the quarantine pests that for first time it were separated
      from the Japan imported tea slips and reported by Maafi (1993). Nowadays it has
      been distributed in some tea growth areas of Guilan and Mazandaran provinces
      (North of Iran). In this study, geographical distribution of this pest is
      reported on some tea growth areas of Guilan province. In order to, 147 samples
      from root and soil around them were investigated. These samples were gathered
      from various gardens of Guilan province. They were transferred to nematology lab
      with suitable temperature and moisture conditions and were stored at 5-10 degrees
      C until extraction time. Centrifugal methods for nematode extraction from soil
      (Jenkins, 1964) and from root (Coolen & D'Herde, 1972) were used. The nematode
      was identified by Handoo & Golden (1989) and Frederick & Tarjan (1989) diagnostic
      keys. According to this study different infested areas and geographical
      distribution were detected in Guilan province. Results indicated that many
      important tea growth areas in Guilan were infested by this nematode. In addition,
      it seems that it has been distributed during short time.

PMID- 16628935
TI  - Study on infection symptoms of root-knot nematode, Meloidogyneja vanica, on the
      stem of the tomato seedlings in greenhouse.
AB  - On the first of seeds germination, Meloidogyne javanica induced knots on the stem
      eventually by to penetrate into the coleoptiles. In this experiment, used soil
      was loamy-sandy type, pH=7.2, including 1.5% composts. Tomato seedlings of
      cultivar Rutgers were used as host. This experiment was conducted in Completely
      Randomized Design with 3 treatments and 10 replicates as fallow: (1) control, (2)
      10 J2s/cm3 of soil, (3) 20 J2s/cm3 of soil. In each pot (1000 cm3), 50 seeds were
      planted. Inoculation was done, a day after to plant seeds, in 2 cm depth. Pre
      emergence and post-emergence damping-off, number of stem-knots, height of knots
      on the stem in 3 treatments was more than 2 treatments. In some of the pots of 2
      treatments were not observed stem-knots. As long as four weeks after planting,
      there was not significant difference in fresh weight and height of the seedlings
      in treatments. Numbers of adult females in 3 treatments were more than 2. In the
      stem-knots, collenchymas tissue, endodermis and stem cambium were found deformed
      J2s and J3s, and adult females.

PMID- 16628936
TI  - Phylogeny of certain biocontrol agents with special reference to nematophagous
      fungi based on RAPd.
AB  - A number of phylogenetic studies have been carried out on biocontrol agents
      having similar biological control activity. However, no work has been carried out
      to determine the phylogenetic relationship amongst various groups of biological
      control agents with varied biocontrol properties. Our aim was to derive a
      phylogenetic relationship between diverse biocontrol agents belonging to the
      deuteromycetes and determine its correlation with their spore morphology and
      their biocontrol activity. RAPD was used to assess genomic variability in fungi
      used as biological control agents which included ten isolates of nematophagous
      fungi such as Arthrobotrys sp., Duddingtonia sp., Paecilomyces sp. and
      Verticillium sp., along with two isolates of fungal biocontrol agents such as
      Trichoderma sp. and two isolates of entomopathogenic fungi including Beauveria
      sp. A plant pathogenic fungus, Verticillium alboatrum was also included to
      increase the diversity of Deuteromycetes used. A similarity matrix was created
      using Jaccard's similarity coefficient & clustering was done using unweighted
      pair group arithmetic mean method (UPGMA). The final dendogram was created using
      a combination of two programs, Freetree and TreeExplorer. The phylogenetic tree
      constructed from the RAPD data showed marked genetic variability among different
      strains of the same species. The spore morphologies of all these fungi were also
      studied. The phylogenetic pattern could be correlated with the conidial and
      conidiophore morphology, a criterion commonly used for the classification of
      fungi in general and Deuteromycetes in particular. Interestingly, the inferred
      phylogeny showed no significant grouping based on either their biological control
      properties or the trapping structures amongst the nematophagous fungi as reported
      earlier by other workers. The phylogenetic pattern was also similar to the tree
      obtained by comparing the 18S rRNA sequences from the database. The result
      clearly indicates that the classical method of classification of these
      deuteromycete members on the basis of their spore morphology is reliable and
      could be used for identification of these fungi at species level. The PCR
      fragment pattern polymorphism exhibited by the various species of a genus and
      different strains of a species indicates that construction of probes from one or
      more of these fragments will prove to be useful as a rapid tool for
      identification of species and strains of nematophagous fungi in future.

PMID- 16628937
TI  - Biological control potential of the obligate parasite Pasteuria penetransagainst
      the root-knot nematode, Meloidogyne incognita infestation in Brinjal.
AB  - The efficacy of the obligate bacterial parasite, Pasteuria penetrans against the
      rootknot nematode, Meloidogyne incognita infestation was assessed in brinjal. The
      seedling pans with sterilized soil were inoculated with nematodes and root powder
      of P. penetrans were applied at different dosages viz., 0 x 10(6), 0.5 x 10(6)
      spores and 1 x 10(6) spores/pan. Seeds of brinjal cv Co2 were sown in the pans
      and seedlings were allowed to grow. The seedlings were transplanted to microplots
      containing sterilized soil. Observations on nematode infestation and plant growth
      were recorded at seedling, flowering, and fruiting stages. Nematode infestation
      was significantly reduced by P. penetrans treatment. There was 22, 75 and 86%
      reduction in nematode population of soil over control at seedling, flowering and
      fruiting stages, respectively, at higher spore density (1 x 10(6)). Egg mass
      production was decreased by 63, 78 and 89% over control at 35 (seedling), 100
      (flowering) and 160 (fruiting) days after sowing respectively, at 1 x 10(6)
      spores treated soil. The parasitizing ability of P. penetrans increased with the
      age of the crop. At higher spore density the percentage of parasitization was
      increased from 52.0 (35 days after sowing) to 90.0 (160 days after sowing) %. At
      these stages of the crop, the spore load per juvenile also increased at the
      higher dose. The P. penetrans application enhanced the plant growth. The weight
      of the shoot was increased by 17.6% whereas root weight by 41.0% over the control
      at fruiting stage. The experimental results revealed the potential use of P.
      penetrans as biological control agent of M. incognita. Application of P.
      penetrans spores in the nursery is a good strategy since the mass multiplication
      is quite difficult.

PMID- 16628938
TI  - Integrated management of root-knot nematode, Meloidogyne incognita infestation in
      tomato and grapevine.
AB  - An integrated approach with the obligate bacterial parasite, Pasteuria penetrans
      and nematicides was assessed for the management of the root-knot nematode,
      Meloidogyne incognita infestation in tomato and grapevine. Seedlings of tomato
      cv. Co3 were transplanted into pots filled with sterilized soil and inoculated
      with nematodes (5000 juveniles/pot). The root powder of P. penetrans at 10 mg/pot
      was applied alone and in combination with carbofuran at 6 mg/pot. Application of
      P. penetrans along with carbofuran recorded lowest nematode infestation (107
      nematodes/200 g soil) compared to control (325 nematodes/200 g soil). The rate of
      parasitization was 83.1% in the carbofuran and P. penetrans combination treatment
      as against 61.0% in the P. penetrans treatment only. The plant growth was also
      higher in the combination treatment compared to all other treatments. A field
      trial was carried out to assess the efficacy of P. penetrans and nematicides
      viz., carbofuran and phorate in the management of root-knot nematode, M.
      incognita infestation of grapevine cv. Muscat Hamburg. A nematode and P.
      penetrans infested grapevine field was selected and treatments either with
      carbofuran or phorate at 1 g a.i/vine was given. The observations were recorded
      at monthly interval. The results showed that the soil nematode population was
      reduced in nematicide treated plots. Suppression of nematodes was higher under
      phorate (117 nematodes/200 g soil) than under carbofuran (126.7 nematodes/200 g
      soil) treatment. The number of juveniles parasitized was also influenced by
      nematicides and spore load carried/juvenile with phorate being superior and the
      increase being 17.0 and 29.0% respectively over the control. The results of these
      experiment confirmed the compatibility of P. penetrans with nematicides and its
      biological control potential against the root-knot nematode.

PMID- 16628939
TI  - Preliminary study of the green algae chlorella (Chlorella vulgaris) for control
      on the root-knot nematode (Meloidogyne arenaria) in tomato plants and
      ectoparasite Xiphinema indexin grape seedlings.
AB  - The alternative ecological methods require investigation of many organo
      biological means for plant protection against dangerous root parasites such as
      root-knot nematode Meloidogyne arenaria and some ectoparasites (Xiphinema index).
      The Bulgarian organic product - dry extract of green alga Chlorella vulgaris
      ("The Golden Apple"-Plamen Barakov) is the latest product, which in comparative
      aspect gives the best results. Series of laboratory and pot experiments are
      carried out with tomato (cv. Bele and cv. Ideal) and grape seedlings (cv.
      Cabernet Sauvignon). Different dosages of Chlorella from 0.5 g to 2 g per
      plant/pot are investigated. The first results show that even low dosages had
      double effect - on the one hand they suppress the parasite development and on the
      other hand they strongly stimulate plant growing. The very important conclusion
      is that Chlorella vulgaris ignores the negative influence of M. arenaria and X.
      index. These results give us opportunity for future model and field
      investigations of Chlorella vulgaris with the aim of its practical application.

PMID- 16628940
TI  - Biodiversity of nematofauna of oilseed rape (Brassica napus L.).
AB  - Few data is available on the nematodes found in Brassicaceae, except for the most
      important plant parasite. However, studying the structure of nematofauna could be
      an important database for the soil quality and in order to assess the effects of
      future disturbance. This is particularly important considering that the diffusion
      of the canola crop in the world is increasing because of its use as a bio-diesel.
      Very diffused is also the Bt variety of oil seed rape, and, in this case, the
      study of the impact on the soil health and on bio-diversity is essential. In this
      research we have analyzed the nematode community, used as a bio-indicator of the
      soil condition. The nematofauna found in canola (Brassica napus var. oleifera)
      fields located in Southern Italy (Metaponto - MT) was investigated. The nematode
      community was studied considering its abundance, genus composition and trophic
      structure. Maturity and biodiversity indices were also calculated. A total of
      5286 nematodes were extracted. They belong to 14 families and 24 genera.
      Bacterial and fungal feeders, 50.18% and 42.90% of the total respectively,
      dominated the trophic structure. Aphelencus is the most abundant genus (23.71%)
      followed by Acrobeloides (20.49%) and Aphelencoides (19.18%). Among plant feeders
      (6.59%), Pratylenchus is the dominant genus (2.20%) and Tylenchidae the main
      family (3.54%). No infestation of Meloidogyne, Heterodera or Naboccus, important
      plant-parasitic nematodes of canola crops, was recorded. Other important
      phytophagous were Helycotylenchus (0.5%), Trichotylenchus (0.5%) and Filenchus
      (0.9%). All of them had an abundance level below injury level. The indices of
      biodiversity are rather low (H'=0.93, J'=0.67), as is typical for agro
      ecosystems. However, the nematofauna community is quite well structured (N2=6.31,
      D=0.16) and the maturity index rather high (EMI=1.94). These values demonstrate
      that oilseed rape has a lower impact on the soil compared to other crop systems
      and that it could be taken into consideration for crop rotation programs. Canola
      could follow other more stressful crops, trying to maintain soil equilibrium.

PMID- 16628941
TI  - Nematodes associated with the rhizosphere of corn (Zea mays L.).
AB  - The research was carried out during 1999 in 8 different localities in Northern
      Italy. The nematodes were extracted from soil samples of rhizosphere of corn
      plants (Zea mays L.). The objective of the study was to investigate plant
      parasite nematodes associated with maize. Some phytophagous genera are common
      pests of this crop and its yield-loss are often due to their high densities. In
      addition the nematode community was investigated for the genus composition, the
      trophic structure and its biodiversity. After the extraction from soil with a
      Bearmann funnel and Ludox centrifugation, nematodes were identified at genus
      level. They belonged to 22 families and 45 different genera. The genus Rhabditis,
      Pratylenchus, Helicotylenchus and Acrobeloides made up more than 70% of the total
      nematodes collected. The dominant trophic group was the bacterial feeders (61%)
      in particular Rhabditis, that was the most abundant and often the dominant one.
      Phytophagous represented in almost all fields more than 30% of the total
      nematodes. In all the examined sites biodiversity was quite low, being the H'
      values no more than 1.08. The data indicates a high level of disturbance. In some
      localities high densities of Helicotylenchus and Pratylenchus were found. While
      these nematodes have been identified as being potentially harmful for corn plants
      in our latitudes, especially in light soils, this research could give an
      indication for further monitoring studies regarding plant parasitic nematodes of
      corn crops. This data is particularly important considering that methyl bromide,
      often used in Italian agriculture against soil pathogens, has been banned since
      the beginning of 2005.

PMID- 16628942
TI  - Spray drift as affected by meteorological conditions.
AB  - Spray drift can be defined as the quantity of plant protection product that is
      carried out of the sprayed (treated) area by the action of air currents during
      the application process. This continues to be a major problem in applying
      agricultural pesticides. The purpose of this research is to measure and compare
      the amount of drift for different climatological conditions under field
      conditions. Spray drift was determined by sampling in a defined downwind area at
      different positions in a flat meadow using horizontal drift collectors
      (sedimenting spray drift) and pipe cleaners (airborne spray drift) for a
      reference spraying. Meteorological conditions were monitored during each
      experiment. A drift prediction equation for the reference spraying was set up to
      predict the expected magnitude of sedimenting drift at various drift distances
      and atmospheric conditions (wind speed and temperature). This equation can be
      used to compare measurements using other spraying techniques under different
      weather conditions to the reference spraying. In 2005, more measurements will be
      performed to validate the statements and the model reflected in this paper.

PMID- 16628943
TI  - Effect of natural windbreaks on drift reduction in orchard spraying.
AB  - In the Netherlands windbreaks are commonly grown to protect orchards against wind
      damage and to improve micro-climate. Natural windbreaks of broad-leaved trees can
      also reduce the risk of surface water contamination caused by spray drift during
      orchard spraying. Spray drift from pesticide applications is a major concern in
      the Netherlands, especially drift into water courses. So far, several drift
      reducing measures have been accepted by water quality control organisations and
      the Board for the Authorization of Pesticides (CTB), e.g. presence of a windbreak
      (i.e. 70% drift reduction at early season and 90% drift reduction at full leaf,
      respectively before and after first of May). From the experiments it was
      concluded that the risk of drift contamination is high during the early
      developmental stages of the growing season. The 70% drift reduction at early
      season as determined in previous experiments, appears to be valid only for
      windbreaks with a certain degree of developed leaves. At full leaf stage 80-90%
      drift reduction by the windbreak was measured. The use of evergreen windbreaks or
      wind-break species that develop in early season can reduce the risk of drift
      contamination considerably. Also, the combination of drift reducing methods, such
      as one-sided spraying of the last tree row and a windbreak is an effective method
      to reduce spray drift in the Netherlands in early season.

PMID- 16628944
TI  - Drift studies--comparison of field and wind tunnel experiments.
AB  - Drift at pesticide application leads to a pollution of non-target crops, non
      target species and surface water. Spray drift is influenced by many factors like
      environmental conditions, vegetation, technical conditions, and physical
      properties of the tank mixes and influenced by Chemicals. Field experiments to
      characterise spray drift effects with the risk of permanent changing weather
      conditions can be supported by wind tunnel experiments. Wind tunnel experiments
      do not lead to the same soil deposition curves like field experiments, but the
      ratio of drift reduction potential is comparable.

PMID- 16628945
TI  - Understanding drift from field spraying: CFD model development.

PMID- 16628946
TI  - Effect of tank mixed adjuvants on the drift potential of phenmedipham
      formulations.
AB  - The aim of this paper is to analyse the effect of adjuvants and formulations on
      drift. The spray liquids consisted of four adjuvants (Actirob 0.4 %, Tensiofix
      0.2%, Breakthru 0.2%, Silwet L-77 0.1%) with water and with two formulations of
      Phenmediphame (C16H16N2O4, 4.45%): an emulsion-forming (EC) and a suspension
      concentrate (SC). A standard flat fan nozzle at a pressure of 3 bar was used. The
      droplet size spectrum of each combination was determined using a Malvern
      granulometer. The droplet size was characterized by the volume median diameter
      (VMD) and the percentage of spray volume contained in droplets <100 microm
      (%<100). The relative drift potential was measured for each combination of
      formulation and adjuvant in a wind-tunnel. This latter has a working section 2.0
      m wide by 2.0 m high by 6.0 m long. The air-stream is drawn by a 1.2 m diameter
      axial flow fan, powered by a 22 kW electric motor. Wind speed was 5 m/s. Its
      uniformity was controlled by a three-dimensional sonic anemometer able to move on
      a linear translation beam placed in the tunnel cross section. The wind-tunnel was
      operated under ambient conditions and three repetitions were performed randomized
      in order to eliminate variations in temperature and humidity for each
      combination. The ground spray deposits were measured on glass fibber collectors
      using a fluorescent tracer dye (sodium fluorescein), at a concentration of 2.5
      mg/l. The statistical analysis of the droplet spectrum showed that the
      Phenmediphame SC formulation generated droplets of higher size than the EC. The
      mean VMD values were respectively equal to 228+/-11 microm and 185+/-11 microm
      for these formulations. For SC formulation, Break-thru decreased the VMD while
      Tensiofix increased the %<100. This confirmed that the degree to which an
      adjuvant influences spray characteristics is very variable. The drift profiles
      produced by the different combinations were similar, but the relative drift
      potential was significantly different comparing SC and EC formulations: it
      respectively reached 0.8+/-0,08% and 1.2+/-0,08%, whatever the adjuvant used in
      the liquid. Clearly, when using a flat fan nozzle to spray Phenmediphame, the
      droplet size and the drift potential are mainly governed by the kind of
      formulation, even if an interaction between the formulation and the adjuvant
      exists.

PMID- 16628947
TI  - Optimisation of sequence and orientation for used nozzles based on few, full boom
      distribution measurements.
AB  - Most studies on uniformity of pesticide applications beneath agricultural
      spraying booms are based on the characteristics of nozzle spray patterns. When
      optimising general features (boom height, pressure, ...), average nozzle
      characteristics are used. In this research, individual nozzle characteristics are
      essential. When utilising slightly used nozzles, small irregularities in the
      nozzle spray distribution may be averaged out or amplified in the resulting full
      boom distribution. A method is proposed to find whether the coefficient of
      variation (cv) of a field sprayer spray distribution could be optimised by
      altering the sequence and orientation of a given set of flat fan nozzles. A
      manageable model is used in order to quickly compute possible full-boom
      distributions (and cv's) with a given set of single nozzle spray distributions.
      The individual nozzle spray distributions are extracted from a limited series of
      full-boom spray distribution measurements (three in most cases) with randomised
      nozzle sequence and orientation by means of a Matlab optimisation algorithm.

PMID- 16628948
TI  - Developments in selective application of herbicides on pavements.

PMID- 16628949
TI  - Development of biofilters to treat the pesticides wastes from spraying
      applications.
AB  - Several studies carried out in Europe showed the importance of direct losses to
      the contamination of surface water by pesticides. These pesticides losses can
      occur at the farm site when the sprayer equipment is filled with the pesticide
      formulation (spills, overflowing, leaking) and during the clean-up (rinsing) of
      the sprayer after the treatment. In Belgium studies are carried out on biofilters
      to treat in an efficient way effluents containing pesticides. The biofilter
      substrate is elaborated from a homogenised mixture of local soil, chopped straw
      and peat or composted material, able to absorb or degrade the active substances.
      Biofilters consist in systems of 2 or 3 units depending on the spray equipment of
      the farmer and on the configuration of the farmyard. Each unit is made from a 1
      m3 plastic container and the different units are stacked in a vertical pile and
      connected between them using plastic valves and pipes. Eight pilot systems were
      installed in March 2002 in seven farms and in one agricultural school, all
      selected in the loamy region of Belgium specialised in arable crops such as
      cereals, sugar beets and vegetables. The efficacy (yield) of the systems was
      determined by measuring the balance of the inputs and outputs of the pesticides.
      Results were expressed in percent of pesticide retained on the biofilters. The
      results obtained after two years with 5 tracer pesticides (atrazine, carbofuran,
      diuron, lenacil and simazine) brought on the biofilter installations are very
      satisfactory since the percentage of retention is generally higher than 95% of
      the amount applied. In the beginning of 2004, ten new pilot biofilters were
      installed in several farms or agricultural technical centres (producing cereals,
      sugar beets, potatoes, vegetables, fruits or ornamental plants), and in a
      municipal maintenance service. Some biofilters were installed in duplicate in
      order to compare the efficacy of different substrates. The efficacy of the
      biofilters was studied for the 5 classical tracer pesticides but also for other
      chemical classes of herbicides (sulfonylurea, aryloxyalcanoic acids,
      chloroacetanilides), insecticides (pyrethroids, carbamates) and fungicides
      (dicarboximides, phenylamides, triazoles and strobilurines). To monitor these
      pesticides in elutes and substrates, two analytical methods were developed,
      optimised and validated : the first one by Gas Chromatography with Mass
      Spectrometry Detection (GC-MS), and the second one by High Performance Liquid
      Chromatography with UV Diode Array Detection (HPLC-DAD). The micro-organisms
      activity in the substrate was also measured in some situations.

PMID- 16628950
TI  - Fate of epoxiconazole and kresoxim-methyl in wheat according to time of
      application.
AB  - During the 2000-2001 season a field trial was conducted with the aim of
      quantifying the distribution and persistence of epoxiconazole and kresoxlm-methyl
      in the different leaf layers of winter wheat plants. In the case of applications
      before flag leaf emergence, the redistribution of the two active ingredients in
      the newly formed leaves following the applications was also measured. Allegro
      (125 g/L epoxiconazole and 125 g/L kresoxim-methyl, SC) was applied at the
      manufacturer's recommended rate (1 L/ha) either in a single treatment at stages
      GS32, GS39 and GS59 or in 2, 3 or 4 split applications. Following spraying, leaf
      samples were collected over time, from each leaf layer, and the two active
      ingredients were quantified by gas chromatography with electron capture detection
      (GC-ECD). Fungicide distribution varies according to time of application. A
      descending gradient through the leaves was observed in the case of application at
      GS59. When sprayed at stage GS39, on the other hand, the second leaf intercepted
      more fungicide than the flag leaf. Kresoxim-methyl was found to degrade faster
      than epoxiconazole. With split treatments, the last spraying appears to be very
      significant in terms of final fungicide quantities. Redistribution appears
      possible, especially in the case of epoxiconazole, though in very small
      quantities.

PMID- 16628951
TI  - A pdpa laser-based measuring set-up for the characterisation of spray nozzles.
AB  - The characteristics of agricultural sprays belong to the most critical factors
      affecting spray drift, deposition on plants, spray coverage and biological
      efficacy. Hence, within the framework of a research project about agricultural
      spray drift, a measuring set-up for the characterisation of spray nozzles using a
      Phase Doppler Particle Analyser (PDPA) was developed. This set-up is able to
      measure droplet sizes and velocities based on light-scattering principles. It is
      composed of different parts i.e.: a climate room, a spray unit, a three
      dimensional automated positioning system and an Aerometrics PDPA 1D system. This
      paper presents a detailed description of this measuring set-up along with some
      first measuring results. These measurements will be used as an input for a
      Computational Fluid Dynamics drift-prediction model and to classify nozzles based
      on their driftability.

PMID- 16628952
TI  - The assessment of spray drift damage for ten major crops in Belgium.
AB  - According to the Council Directive 91/414/EC pesticide damage should be assessed
      by considering the risk for persons arising from occupational, non-dietary
      exposure and risk to the environment. In this research an assessment for the
      pesticide damage by droplet spray drift was set up. The percentages of spray
      drift were estimated with the Ganzelmeier drift curves and the IMAG drift
      calculator. Knowing the percentages of drift and the applied doses of pesticide
      formulations in a given crop, the human and environmental exposures (water and
      bottom) were predicted. Thereupon risk indices were calculated for water
      organisms, soil organisms and bystanders. A risk index is the ratio of a
      predicted exposure to a toxicological reference value and gives an indication of
      the incidence and the severity of the adverse effects likely to occur.
      Considering the risk index it is possible to define the minimal width of an
      unsprayed field margin or "buffer zone" to reduce this risk at an acceptable
      level.

PMID- 16628953
TI  - Toxicity of the ammonium nitrate NH4NO3 on the respiratory metabolism of three
      biological models: parameciums, mosses and lichens.
AB  - The inopportune throws out of diverse substances in the atmosphere, constitutes
      without any doubt the obvious of environmental pollution by man. Among these
      substances, we are interested in the ammonium nitrate NH4NO3, nitrate fertilizers
      widely used in farming in our region - Annaba located in the eastern part of
      Algeria - and manufactured in the same region. In fact, the excessive
      fertilization, the intensive spreading of animal faeces and the industrial
      pollution are the accumulation sources of nitrate in vegetables, drilling and the
      underground waters. The goal of this study is to show the obviousness of a
      possible toxic effect of NH4NO3 on paramecium an inferior plants resed as
      biological models. The tests of toxicity were achieved on samples of the area of
      culture of parameciums. Four concentrations were chosen: 10, 20, 30 and 40 mM,
      and added before and after appearance of the parameciums in the area. The
      prepared solutions with the same concentrations of NH4NO3, were used for the
      dampening of the samples of mosses and lichens. The use of an original technique
      the polarography allowed us to measure the quantity of oxygen consumed by the
      organisms in presence of the polluent. The results show that: (i): The treatment
      by NH4NO3 stimulates the respiratory metabolism of paramecium, (ii): with mosses
      as well as the measure of the consumption of the oxygen shous the abviousness
      contrasted with a dampening of respiration but also of the photosynthesis. The
      perturbation of the respiration and photosynthesis of mousses and lichens can
      explain the degradation of the plant material and the disappearance of certain
      species from our ecosystem.

PMID- 16628954
TI  - Fungicide residues in pears and apples after post harvest treatments by drencher.
AB  - Aim of this trial was to verify the residues of two fungicides, already
      authorised for the use in field (the admitted maximum limit of residues have been
      fixed), after post harvest treatments on pears and apples for defence against
      main post harvest rots. The use of formulation in post harvest must consider also
      the technique of product application. In fact there are different systems to
      carry out the treatments for the protection of the commodities during cold
      storage. In this trial two formulations of pyrimethanil and imazalil were applied
      by drencher on pome fruit.

PMID- 16628955
TI  - Effectiveness and residues of procymidone applied on celery and fennel in the
      control of Sclerotinia sclerotiorum (Lib.) de Bary.
AB  - A biennial experimentation has been led using the active ingredient (a.i.)
      procymidone, for the control of Sclerotinia sclerotiorum (Lib.) De Bary on fennel
      and celery. At present this utilizathion it is not authorized, even though this
      "minor use" is considered essential for the control of the various
      phytopathologies. For every test, both in field and in greenhouse, two treatments
      to the dose of 40 g/hl of a.i. have been made. After the second treatment two
      assessments were led to check effectiveness of a.i. and subsequent vegetable
      samplings have been made to determine the entity and the persistence of the
      residues of the used active ingredient. At the end of the agricultural cycle, in
      all the tests a good control of the infection caused by the fungus has been
      found; statistically significant differences of the infection between treated
      plots and the control. At harvesting (21 days from the 2nd treatment) we have
      found a residue average value of 0.1-0.2 mg/kg (field) and 0.3-0.4 mg/kg
      (greenhouse) on fennel and of: 1.0-1.5 mg/kg (field) e 3.0-3.5 mg/kg (greenhouse)
      on celery.

PMID- 16628956
TI  - Fungicide residues in pears, apples and grapes after post harvest treatments by
      thermonebulization.
AB  - In the context of trials conducted in cold store, in order to investigate
      efficacy of fruit protection applying agrochemicals, the fate during the storage
      of two active ingredients (a.i.): pyrimethanil and imazalil, have been studied.
      The experimental trials were done on eight varieties of apples and pears and two
      of grapes. Only field use of named pesticides was already authorised on fruits
      and maximum residue limits (MRL) fixed. In the present biennial experimentation
      (apples and pears in the first year; grapes in the second one). Two fungicides
      formulations were applied and treatments have been executed by thermonebulization
      technique. The storage cell, had a volume of 110 m3 filled up with the fruits
      until 80% of its capacity. Each fruit variety constituted one thesis of 4
      replicates. For each trial, only one treatment was performed at the beginning of
      conservation period (72 days for pears and apples, and 57 days for grapes). In
      order to estimate fungicides persistence, residues determinations have been
      carried out. From results obtained especially on grape, not homogenous residues
      distribution on treated commodities was observed. For all theses, residue level
      has not evidenced statistically significant decrement as function of time,
      behaviour not as observed in field tests. The following average values of
      residues have been determined: in apples and pears, 0.7 mg/kg of imazalil much
      lower than 5 mg/kg (RML fixed for field use), and 1.2 mg/kg of pyrimethanil
      little higher than 1 mg/kg (RML fixed for field use); in grapes 0.5 mg/kg
      pyrimethanil much lower than 3 mg/kg (RML fixed for field use).

PMID- 16628957
TI  - Early embryogenesis study on a dimethoate containing formulation and Cd-sulphate
      in chicken embryos.
AB  - The toxic effects of a widely used organophosphate insecticide (BI 58 EC
      containing 38% dimethoate as active ingredient) applied alone or in combination
      with cadmium sulphate modelling the heavy metal load of the environment were
      studied on chicken embryos in the early phase of development. Solutions and
      emulsions of different concentrations were made from the test materials and
      injected in 0.1 ml volume into the air space of eggs on the first day (day 0) of
      incubation. Subsequently, on days 2 and 3 of incubation permanent preparations
      were made from the embryos in order to study the early developmental stage.
      Embryos fixed on slides and stained with osmium tetroxide solution were studied
      under light microscope. Summarising the findings, it can be established that the
      embryotoxicity increased after the simultaneous administration of Cd-sulphate and
      38% dimethoate containing insecticide formulation compared to the control or the
      individually treated groups.

PMID- 16628958
TI  - Determination of chlorprophame residues in potatoes by GC-NPD or GC-MS.

PMID- 16628959
TI  - Multi-residue method for determination of pesticides residues in potatoes by GC
      NPD.

PMID- 16628960
TI  - Environmental impact of adjuvants in crop protection.
AB  - The overall performance of chemical and biological plant protection products is
      enhanced by the use of adjuvants in the formulation (formulation adjuvants) or in
      the spray tank (spray adjuvants). Both types of adjuvants aim to stabilize the
      formulation, to improve the efficiency of the active ingredients and to reduce
      application and environmental risks. As an important part of the formulation,
      both quantitatively and qualitatively, the environmental impact and toxicology of
      adjuvants can not always be considered as inert. However, little is known of
      their impact as part of plant protection products compared with the active
      substances. Therefore an experimental framework is needed as a tool for a
      consistent environmental legislation.

PMID- 16628961
TI  - [Drug safety of NSAIDs and COX-2 inhibitors].
AB  - In this review the risk-benefit ratio of COX-2 inhibitors and NSAIDs is compared.
      In the discussion of the safety of these two groups different evaluation
      standards are used, which is not a basis of a rational pharmacotherapy.

PMID- 16628962
TI  - [Dry mouth].
AB  - Dryness of the mouth (xerostomia) is a serious problem for the affected patients,
      in particular if it is caused by a reduced salivation. Triggering factors are,
      e.g., drugs (antihypertensives, neuroleptics), CNS disorders, chronic obstruction
      of nasal breathing, irradiation therapy of head-neck tumors, Sjogren's syndrome,
      sarcoidosis, or diabetes mellitus. Patients with xerostomia should be diagnosed
      and treated on an interdisciplinary basis. Several causal and symptomatic
      therapeutic options are available, including local stimulation of salivation. In
      addition, prevention is to be emphasized. In most patients symptomatic
      improvement and thus an improved quality of life can be achieved.

PMID- 16628963
TI  - [Drug interactions of tacrolimus].
AB  - Allogeneic hematopoetic stem cell transplantations can be complicated by a graft
      versus-host disease (GvHD), i.e., immunocompetent cells from the transplanted
      bone marrow act against solid organs of the recipient. A GvHD is treated with
      immunosuppressants. Consequently, further drugs are required, for example in
      order to prevent infections and result in in polymedication of those patients
      with a risk of drug interactions. In this case report, drug interactions between
      tacrolimus and concomitant therapy in a stem-cell-transplanted patient are
      discussed.

PMID- 16628964
TI  - [What should we give for an actual tetanus infections, when should a new
      vaccination be given?].

PMID- 16628965
TI  - Free clinic serves uninsured.

PMID- 16628967
TI  - Management of postpartum uterine atony.

PMID- 16628966
TI  - Numbers don't bode well for programs.

PMID- 16628968
TI  - Wisconsin Environmental Health Network--a new resource for Wisconsin physicians.

PMID- 16628969
TI  - Nanomaterial health effects--part 1: background and current knowledge.
AB  - Nanotechnologies are among the fastest growing areas of scientific research, and
      have important applications in a wide variety of fields. At the same time,
      scientists and regulators are concerned about the potential health and
      environmental risks related to the widespread production and use of the
      nanomaterials created by these technologies. Several recent animal and cell
      culture studies have suggested that some engineered nanomaterials may have
      biological effects similar to ultrafine particulates. This paper describes what
      nanomaterials are and why they might be toxic, and then reviews existing
      toxicological studies on engineered nanomaterials.

PMID- 16628970
TI  - Trends in occupational and adult lead exposure in Wisconsin 1988 - 2005.
AB  - Seventeen years of adult blood lead surveillance data (37,694 individuals and
      71,622 total tests) reveal a Wisconsin success story. While lead continues to be
      widely used, most Wisconsin industries have made substantial strides toward
      reducing occupational lead exposure. The improvement is reflected in the reduced
      number of blood lead levels >40 microg/dL. In 2005 only a single adult blood lead
      test was >50 pg/dL, and since 2003 none have been reported above 60 microg/dL.
      However, as long as lead is used industrially, lead-based products remain in use,
      and new consumer products containing lead are marketed to the public, lead
      poisoning will remain a threat, not only to workers handling lead, but also to
      children exposed to lead-containing products already in existence. Wisconsin
      industry and workers, as well as the medical and public health community, must
      remain vigilant about new and reemerging lead exposures. Wisconsin's Adult Blood
      Lead Epidemiology and Surveillance program will continue to investigate unusual
      lead exposure circumstances identified through statutorily mandated physician and
      laboratory reporting of adult blood lead levels. However, Wisconsin will need
      further advances if it is to achieve the US Healthy People 2010 objective of no
      adult blood lead level >25 microg/dL.

PMID- 16628971
TI  - Status of work-related diseases in Wisconsin: five occupational health
      indicators.
AB  - Direct and indirect costs of work-related injuries and illnesses in the United
      States are estimated to cost over dollar 170 billion annually. Wisconsin's costs
      alone may be as high as dollar 1 billion annually. Considering the magnitude of
      these costs, it is disconcerting that there is no national surveillance program
      to track the occupational injuries, illnesses, and hazards responsible.
      Surveillance is an essential public health function and the foundation for
      recognizing and then designing and evaluating interventions to reduce the
      consequences of identified hazards. Wisconsin has a rudimentary occupational
      injury and illness surveillance program. It has recently been strengthened by
      receipt of a 3-year fundamental surveillance grant from the National Institute
      for Occupational Safety and Health (NIOSH). As part of that grant, Wisconsin will
      begin tracking 19 NIOSH occupational health indicators. In this paper we measured
      5 occupational health indicators for Wisconsin: Pneumoconiosis hospitalizations,
      Pneumoconiosis mortality, Acute work-related pesticide poisonings, Incidence of
      malignant mesothelioma, and Elevated blood lead levels among adults. Year 2000
      baseline results of these 5 occupational disease indicators show that Wisconsin
      has lower disease rates than the nation for some of the indicators and higher
      rates for others. Such surveillance data informs the understanding of
      environmental and other important risk factors for occupational diseases and
      injuries.

PMID- 16628972
TI  - Linking childhood cancer with potential environmental exposure determinants.
AB  - Childhood chronic diseases, especially cancer, are of growing concern. Research
      has focused on 2 developmental periods, prenatal and postnatal. While it is
      hypothesized that chemical contaminants in the physical environment may play a
      role in the development and exacerbation of many chronic diseases, the role of
      environmental exposures in the etiology of these conditions remains uncertain.
      This can be somewhat attributed to the fact that it is very difficult to
      efficiently link chronic health effects with environmental exposures that are
      likely to have occurred temporally and spatially distant from diagnosis. This
      study explored the utility of linking childhood cancer cases with their birth
      certificate data as a method for increasing the number of geo-referenced data
      points available for linking health effect data with environmental monitoring
      data. This would begin to quantify the transiency of 1 subset of the population,
      and provide a basis for characterizing and estimating potentials for exposure to
      numerous environmental contaminants during prenatal and postnatal periods. A
      total of 441 unduplicated cancer diagnosis records of children who were both born
      and diagnosed with cancer in Wisconsin between 1995 and 2002 were linked with
      birth records to explore the variability between address at birth and diagnosis.
      The majority of records were matched to a birth record file (81.0%). Of these
      matched records, 86% moved <1 mile from birth to time of diagnosis. The results
      suggest that administrative and public health surveillance data can be used to
      quantify transiency. Data from the sample tested indicate that during the given
      time period children do not move far from their birth homes, suggesting minimal
      changes in exposure potential related to residence location from birth to
      diagnosis. This background is useful for future epidemiological investigations
      linking environmental factors with chronic health effects.

PMID- 16628973
TI  - Evaluation of five data sources for inclusion in a statewide tracking system for
      accidental carbon monoxide poisonings.
AB  - All accidental carbon monoxide poisoning should be preventable. Yet despite
      intervention efforts including promotion of inexpensive home carbon monoxide
      detectors, annual inspection of home gas and oil appliances, and general
      awareness campaigns, in 2002 there were 18 fatalities, 36 inpatient admissions,
      351 emergency department visits and 117 poison center calls attributed to acute
      carbon monoxide exposure. The first step to help better focus public health
      interventions is adequate information on occurrences. The Wisconsin Environmental
      Public Health Tracking program identified and evaluated potential data sources
      for inclusion in a surveillance system for monitoring unintentional carbon
      monoxide poisonings. Criteria to evaluate the utility of the existing data
      systems were developed and included the number of new cases identified from that
      source, the circumstantial detail provided, timeliness of data availability,
      confidence that an actual exposure occurred, and the resources required to
      retrieve and summarize the data. Five candidate datasets were evaluated:
      emergency department visits, hospital inpatient stays, death certificates,
      Wisconsin Poison Center records, and newspaper reports. It was found that
      although there was some overlap between cases reported in the different datasets,
      each source provided unique cases. The sources also differed in the resources
      required for utilizing the data and the amount of circumstantial information
      provided. Based on the evaluation of the different sources, it was concluded that
      newspaper reports should not be included, but the other 4 data sources would each
      contribute substantially to establishing a comprehensive surveillance system for
      accidental carbon monoxide poisoning.

PMID- 16628974
TI  - Fish consumption and advisory awareness among expectant women.
AB  - During the spring of 2003, the Wisconsin Department of Health and Family Services
      (DHFS) piloted a fish consumption advisory program targeted at pregnant women.
      Fish consumption recommendations and information about the prenatal effects of
      methylmercury were illustrated in multilingual posters, brochures, fact cards,
      and other promotional items. These materials were mailed to Women, Infants and
      Children (WIC) program providers, local health departments, and medical clinics,
      along with a cover letter that encouraged them to display the materials in
      waiting areas and distribute them to new mothers and expectant women who visited
      their facilities. In August 2003, a survey was mailed to 1000 women who had given
      birth during the first week of June 2003. The survey was intended to provide an
      estimate of the number and types of fish meals the women had consumed during
      pregnancy and evaluate their familiarity with the outreach materials. On average,
      survey respondents consumed 3 fish meals a month. The most frequently consumed
      fish were canned tuna and frozen fish. Approximately one third of women knew that
      older fish and predatory fish have the highest levels of mercury. While almost
      half of the women were aware of Wisconsin's sport fish advisory, only 13% of them
      remembered seeing any of the outreach materials.

PMID- 16628975
TI  - Pediatrician attitudes, clinical activities, and knowledge of environmental
      health in Wisconsin.
AB  - Pediatricians can reduce exposures to environmental hazards but most have little
      training in environmental health. To assess whether Wisconsin pediatricians
      perceive a relative lack of self-efficacy for common environmental exposures and
      diseases of environmental origin, we assessed their attitudes and beliefs about
      the role of the environment in children's health. A 4-page survey was sent to the
      membership of the Wisconsin Chapter of the American Academy of Pediatrics. We
      obtained a 35.4% response rate after 1 follow-up mailing. Respondents agreed that
      the role of the environment in children's health is significant (mean 4.28 +/-
      .78 on 1-5 Likert scale). They expressed high confidence in dealing with lead
      exposure (means 4.22-4.27 +/- 1.01-1.09), but confidence in their skills for
      pesticide, mercury, and mold was much lower (means 2.49-3.09 +/- 1.06-1.26;
      P<.001). Of those surveyed, 88.6% would refer patients to a clinic "where
      pediatricians could refer patients for clinical evaluation and treatment of their
      environmental health concerns." These findings indicate that Wisconsin
      pediatricians agree that children are suffering preventable illnesses of
      environmental origin, but feel ill equipped to educate families about many common
      exposures. Significant demand exists for centers that can evaluate environmental
      health concerns, as well as for educational opportunities.

PMID- 16628976
TI  - The National Children's Study and the children of Wisconsin.
AB  - Prospective, multi-year epidemiologic studies such as the Framingham Heart Study
      and the Nurses' Health Study have proven highly effective in identifying risk
      factors for chronic illness and in guiding disease prevention. Now, in order to
      identify environmental risk factors for chronic disease in children, the US
      Congress authorized a National Children's Study as part of the Children's Health
      Act of 2000. Enrollment of a nationally representative cohort of 100,000 children
      will begin in 2008, with follow-up to continue through age 21. Environmental
      assessment and examination of biomarkers collected at specified intervals during
      pregnancy and childhood will be a major component of the Study. Recruitment at
      105 sites across the United States is planned, and will begin at 7 Vanguard
      Centers in 2008, including Waukesha County, Wis. The National Children's Study
      will provide information on preventable risk factors for such chronic diseases as
      asthma, certain birth defects, neurobehavioral syndromes, and obesity. In
      addition, the National Children's Study will provide training in pediatric
      environmental health for the next generation of researchers and practitioners.

PMID- 16628977
TI  - The National Children's Study Waukesha County, Wisconsin Vanguard Center.
AB  - The National Children's Study (NCS) is a large, longterm study designed to detect
      environmental influences on the health and development of children. Waukesha
      County, Wisconsin, was selected as 1 of 7 "Vanguard Centers" currently funded to
      finalize and lead the implementation of the study protocol. The authors provide
      an overview of key design and planning processes that will be used at all NCS
      Vanguard locations, the specific approaches to be used in the NCS Waukesha County
      Vanguard Center, and information about how Wisconsin physicians and other health
      care professionals can become involved in working with the NCS.

PMID- 16628978
TI  - National Children's Study: environmental exposures in Waukesha County.
AB  - The National Children's Study (NCS), launched in September of 2005, will
      investigate the effects of environmental exposures and children's health and
      development. Waukesha County, Wis was selected as 1 of 7 sites to spearhead this
      ambitious undertaking. Residents of Waukesha County may experience different
      kinds of environmental exposures from water, land, and air based on where they
      live, work, and play. A selected number of Waukesha County's environmental
      exposures described briefly in this report will serve the NCS well with their
      heterogeneity of potential exposures: from private well water and community water
      supplies that obtain water from both surface and groundwater; from the variable
      exposures to ambient air pollution from mobile sources, local industrial sources,
      and distant sources (ozone); and the different levels of exposures from soil and
      dust depending on the prevalence of pesticide use and lead-based paints. By
      combining data gathered from Waukesha County's participants with other study
      sites, a holistic picture of environmental exposures in the United States can be
      evaluated as it influences the health of our nation's children.

PMID- 16628979
TI  - Uterine rupture in a patient with an unscarred uterus: a case study.
AB  - Uterine rupture is a true obstetrical emergency. We present a case of a
      multigravid woman who had a spontaneous uterine rupture after induction with
      misoprostol and oxytocin, followed by a general discussion of uterine ruptures
      with a special emphasis on an unscarred uterus. Risk factors for uterine rupture
      in an unscarred uterus include grand multiparity, induction with misoprostol or
      oxytocin, malpresentation, or previous surgical abortion. Most cases present with
      maternal tachycardia, signs of fetal distress, and bleeding. The treatment for
      intrapartum uterine rupture includes fluid resuscitation and emergency
      laporotomy. Postpartum counseling regarding the risk of rerupture with subsequent
      pregnancies is an important piece of the management of these patients.

PMID- 16628980
TI  - Simulations enhance clinical aptitude in high-tech training facility.

PMID- 16628981
TI  - Be aware of fiduciary responsibilities with retirement plans.

PMID- 16628982
TI  - The Malthusian theory.

PMID- 16628983
TI  - The case: your diagnosis? Calcific tendonitis of the fibular collateral ligament.
AB  - This article describes calcific tendonitis within the fibular collateral
      ligament, presumably from hydroxyapatite deposition, a rare cause of acute,
      severe lateral knee pain. Imaging findings confirmed calcifications in an intact
      but thickened fibular collateral ligament with adjacent soft-tissue reaction,
      consistent with calcific tendonitis. Magnetic resonance imaging can appear
      aggressive, and therefore the findings often can be mistaken for other knee
      abnormalities; specifically, the presentation following a twisting injury that
      requires avulsion fracture or ligamentous injury be excluded. Confirmation of
      crystal deposition with thin-section CT is helpful when suspected on MRI because
      it is unequivocal in depicting calcifications and bony detail.

PMID- 16628984
TI  - Measuring angles.

PMID- 16628985
TI  - On the attainment of board certification.

PMID- 16628986
TI  - The effect of RFE after arthroscopy.

PMID- 16628987
TI  - Offensive defensive medicine.

PMID- 16628988
TI  - Modified Galeazzi technique for recurrent patellar dislocation in children.

PMID- 16628989
TI  - Evaluation of elbow flexion and linel tests for cubital tunnel syndrome in
      asymptomatic individuals.

PMID- 16628990
TI  - Dietary supplement and selected food interactions with warfarin.

PMID- 16628991
TI  - Percutaneous osteoplasty for pelvic and spine metastases.

PMID- 16628992
TI  - Chronic seroma in the posterior leg compartment of a college football player.

PMID- 16628993
TI  - Perioperative infection control: an update for patient safety in orthopedic
      surgery.

PMID- 16628994
TI  - Results of an alternative autogenous iliac crest bone graft harvest method.
AB  - This article reports the results using a previously described technique of
      obtaining iliac crest bone graft using an acetabular reamer in a consecutive
      series of patients with complex acute traumatic injuries and nonunions. A
      retrospective chart review was conducted on a cohort of 34 consecutive patients
      who underwent complex orthopedic procedures for the definitive management of
      acute or reconstructive problem fractures and nonunions using autogenous iliac
      crest bone graft. All of the patients had autogenous bone graft prepared using a
      low speed, high torque power source and small acetabular reamers. The inner or
      outer wall of the ileum or the posterior superior iliac spine was reamed
      providing a large volume of corticocancellous graft. This material was used to
      pack defects in established nonunions, to augment plate osteosynthesis in
      segmental fractures, or to facilitate arthrodesis. Follow-up averaged 10 months
      (range: 6-18 months). Thirty-three out of 34 patients went on to uneventful
      union. No patients experienced morbidity from the graft harvest site.
      Specifically, no patients developed a superficial or deep wound hematoma or
      infection, nor did they experience persistent donor-site pain or paresthesias.
      Autogenous iliac crest bone graft harvest using the reaming technique provides a
      large volume of corticocancellous graft that has proven effective in treating
      complex acute nd reconstructive trauma cases.

PMID- 16628995
TI  - Postoperative clinical results in cubital tunnel syndrome.
AB  - This article reports on factors affecting the postoperative results in cubital
      tunnel syndrome. We evaluated 111 limbs of 107 patients who had been surgically
      treated for cubital tunnel syndrome. Average patient age was 43.9 years (range:
      11-77 years). Postoperative follow-up ranged from 1 to 17 years (mean: 5.2
      years). Causal diseases included cubitus valgus following fractures in childhood
      in 43 limbs, osteoarthritis in 45 limbs, and others in 23 limbs. Surgical
      treatment involved King's method for 66 limbs, anterior transposition for 41
      limbs, and Osborne's method for 4 limbs. Preoperative severity and postoperative
      results were evaluated according to the critera for evaluation of ulnar nerve
      palsy of Yokohama City University. Preoperative severity was stage I in 19 limbs,
      stage II in 12 limbs, stage III in 41 limbs, and stage IV in 39 limbs.
      Postoperative results at final evaluation were excellent in 37 limbs, good in 39
      limbs, fair in 26 limbs, and poor in 9 limbs. Age at surgery, duration of cubital
      tunnel syndrome, preoperative severity, and clinical symptom score and motor
      nerve conduction velocity in the early postoperative stage (one month after
      surgery) were found to be important prognostic factors of the syndrome.

PMID- 16628996
TI  - High energy tibial plateau fractures treated with hybrid fixation: is knee
      bridging necessary?
AB  - This article assesses the necessity of knee bridging in high-energy tibial
      plateau fractures treated with ring or hybrid frames. One hundred twelve tibial
      plateau fractures were treated with hybrid fixation. Thirty fractures underwent
      simple tibial fixation and 82 fractures required provisional extension of the
      femoral fixation. Mean follow-up was 5 years (range: 28 months to 13 years).
      Seventy-three percent of the injuries had at least one indication for fixation
      and 57% had more than one indication for tibiofemoral fixation. The most common
      indications include comminution, soft-tissue compromise, and ligamentous
      injuries. The majority of high-energy tibial plateau fractures are associated
      with such injuries that require knee bridging. Fixed tibiofemoral fixation offers
      better subjective, clinical, functional, and radiologic results.

PMID- 16628997
TI  - The incidence of rotator cuff disease in smoking and non-smoking patients: a
      cadaveric study.
AB  - The etiology of rotator cuff disease is multifactorial. One theory behind the
      high incidence of rotator cuff tears in the shoulder is that the
      supraspinatus/infraspinatus tendon contains a zone of relative avascularity in
      the area proximal to its insertion at the greater tuberosity. Tobacco smoking is
      known to contribute to microvascular disease, and it can be hypothesized that
      smoking tobacco further compromises the vascular supply to the
      supraspinatus/infraspinatus tendon, thus increasing the incidence of tendinous
      pathology in the rotator cuff. This article evaluates the rotator cuffs of 72
      shoulders in 36 cadavers and compares the incidence of macroscopic and
      microscopic disease within the rotator cuff tendon. Microscopic evaluation of the
      accompanying lung tissue from the respective cadaver also was performed. As a
      result, we were able to determine the presence or absence of a smoking history or
      emphysema from each cadaver as it related to rotator cuff disease in the
      shoulder. Of the 36 shoulders that exhibited macroscopic rotator cuff tears, 23
      were from cadavers with a history of smoking compared to only 13 from cadavers
      with no history of smoking. Furthermore, the presence of advanced microscopic
      rotator cuff pathology (Grade 3 or 4 fibrous degeneration) was more than twice as
      likely in the cadavers with a history of smoking (22/32) compared to only 10 of
      32 shoulders from cadavers with no history of smoking. While none of this data
      was statistically significant due to the insufficient number of subject cadavers,
      strong trends were noted in these findings.

PMID- 16628998
TI  - Angiomyolipoma of the hallux.

PMID- 16628999
TI  - Surgical treatment for atlantoaxial subluxation associated with mixed connective
      tissue disease.

PMID- 16629000
TI  - Fibrous dysplasia of the fourth metacarpal: en-bloc resection and free metatarsal
      transfer.

PMID- 16629001
TI  - Mary K. Salazar, EdD, RN, COHN-S, FAAOHN, FAAN--Editor, Core Curriculum for
      Occupational and Environmental Health Nursing. Interview by Eileen Lukes.

PMID- 16629003
TI  - Prevention and control of infectious diseases in the workplace.

PMID- 16629004
TI  - The National Occupational Research Agenda--the second decade of NORA.

PMID- 16629005
TI  - Risk factors associated with work-related musculoskeletal disorders among female
      flight attendants: using a focus group to prepare a survey.
AB  - In preparation for surveying female flight attendants about work-related
      musculoskeletal disorder risk factors and symptoms, a focus group study was
      completed with members of the target population. The aims of this study were to
      ensure completeness of a previously developed list of physically strenuous job
      tasks performed by female flight attendants and assess the clarity,
      appropriateness, and applicability of existing self-reported measures to be used
      in the survey. Female flight attendants who worked one or more long-haul
      international flights in the prior 3 months and 75 or more hours in the prior
      month were recruited from the union membership. A trained moderator led a 2-hour
      discussion with the flight attendants. With use of a transcript-based analysis, a
      final list of 41 job tasks was created. Useful comments on a set of self-reported
      measures were obtained. The

PMID- 16629006
TI  - Staging workers' use of hearing protection devices: application of the
      transtheoretical model.
AB  - The threat of noise-induced hearing loss is a serious concern for many workers.
      This study explores use of the transtheoretical model as a framework for defining
      stages of workers' acceptance of hearing protection devices. A secondary analysis
      was performed using a cross-section of data from a randomized, controlled
      clinical trial of an intervention to increase use of hearing protection. Use of
      hearing protection devices was well distributed across the theorized stages of
      change. Chi-square analysis and analysis of variance revealed significant
      differences between stages for the variables studied. Discrete stages of hearing
      protection device use can be identified, laying the foundation for further work
      investigating use of the transtheoretical model for promoting hearing protection
      device use. The model can provide a framework for tailoring interventions and
      evaluating their effects. With further development of the transtheoretical model,
      nurses may be able to easily identify workers' readiness to use hearing
      protection devices and tailor training toward that goal.

PMID- 16629007
TI  - Friction-reducing devices for lateral patient transfers: a clinical evaluation.
AB  - The purpose of this study was to assess the performance of lateral transfer
      devices compared with the traditional draw sheet method in acute care settings
      through subjective feedback of caregivers actually using the devices. Every 2
      weeks, the eight participating acute care units each received one of the devices,
      which had been randomly selected. Data were collected through caregiver surveys,
      which rated comfort, ease of use, perceived injury risk, time efficiency, and
      patient safety. An overall performance rating was calculated as the sum of these
      five categories. Caregivers rated air-assisted devices significantly higher (p <
      .05) than other devices. Lateral transfer devices are recommended over the
      traditional draw sheet method for performing lateral patient transfers. These
      friction-reducing devices are a cost-effective solution to the load of lateral
      patient transfers and should be favorably considered when purchasing patient
      handling technologies.

PMID- 16629008
TI  - Juggling work and elder caregiving: work-life balance for aging American workers.
AB  - As the American work force ages, the demands of caring for aging relatives
      increase. Family caregiving often interferes with workplace responsibilities,
      creating physical, emotional, and financial stress for caregivers. Employers must
      address the productivity losses created by absenteeism of workers who struggle
      with work-life issues created by caregiving roles. Occupational health nurses
      must understand the factors that affect workers in their caregiving roles and
      make appropriate nursing interventions. They are in key positions to help aging
      employees and their employers face the increased demands on work-life balance
      created by elder caregiving.

PMID- 16629009
TI  - Promoting eye health--prevention and detection of cataracts.

PMID- 16629010
TI  - Growth of Salmonella Enteritidis phage type 30 in almond hull and shell slurries
      and survival in drying almond hulls.
AB  - Traceback investigation of a 2000 to 2001 outbreak of salmonellosis associated
      with consumption of raw almonds led to isolation of the outbreak strain
      Salmonella enterica serovar Enteritidis phage type (PT) 30 on three
      geographically linked almond farms. Interviews with these growers revealed that
      significant rain fell during the 2000 harvest when many almonds were drying on
      the ground. The objectives of this study were to document weather conditions
      during the 2000 harvest, determine the potential for growth of Salmonella
      Enteritidis PT 30 in hull or shell slurries, and evaluate survival of Salmonella
      Enteritidis PT 30 on wet almond hulls during drying. Dry almond hulls and in
      shell kernels wetted for 24 h increased in weight by 250 to 300% and 100%,
      respectively. Both hull and shell slurries supported rapid growth of Salmonella
      Enteritidis PT 30 at 24 degrees C; slurries containing hulls also supported
      growth at 15 degrees C. Maximum Salmonella Enteritidis PT 30 concentrations of
      6.2 and 7.8 log CFU/ml were observed at 15 and 24 degrees C, respectively.
      Salmonella Enteritidis PT 30 grown in wet hulls that were incubated at 24 degrees
      C survived drying at either 15 or 37 degrees C. Reductions of 1 to 3 log CFU/g of
      dry hull were observed during drying; reductions generally declined as incubation
      time increased from 2 to 7 days. Evaluation of shipping records revealed that
      approximately 60% of outbreak-associated almonds had not been exposed to rain,
      eliminating this factor as the sole cause of the outbreak. However, the data
      provide evidence that wet almonds may be a greater risk for high concentrations
      of Salmonella, and specific guidelines should be established for harvesting and
      processing almonds that have been exposed to rain or other water sources.

PMID- 16629011
TI  - Inhibition of Salmonella enterica by plant-associated pseudomonads in vitro and
      on sprouting alfalfa seed.
AB  - Foodborne illness due to the consumption of contaminated raw or lightly cooked
      sprouts is a continuing food safety concern. In this study, we tested several
      plant-associated pseudomonads for their ability to inhibit the growth of
      Salmonella enterica both in vitro and in situ. An agar spot bioassay method was
      used with three different media. Only Pseudomonas fluorescens 2-79 produced clear
      zones of inhibition when tested against five serovars of S. enterica, and
      activity was dependent on media type and serovar. The antibiosis by derivative
      strains of P. fluorescens 2-79 defective in the production of phenazine-1
      carboxylic acid and fluorescent siderophore was not reduced, indicating that
      these known antimicrobial metabolites were not responsible for the inhibition
      observed in our studies. However, mutants defective in the regulatory gene gacS
      (global antibiotic and cyanide control) were severely reduced in inhibitory
      activity. In tryptic soy broth, the control cultures of a cocktail of S. enterica
      strains reached approximately 10 log CFU/ml by 24 h but, when coinoculated with
      P. fluorescens 2-79, reached only approximately 5 log CFU/ml. The addition of P.
      fluorescens 2-79 to the seed soak water prior to the germination of alfalfa seed
      previously inoculated with a cocktail of S. enterica strains led to an average
      reduction of 5 log CFU/g at 6 days of sprouting without an adverse effect on
      sprout yield or appearance. Time course studies indicated that S. enterica
      outgrowth was controlled on days 1 through 6 of sprouting. Competitive exclusion
      as a potential food safety intervention for seed sprouts merits further study.

PMID- 16629012
TI  - Identifying the components in eggshell membrane responsible for reducing the heat
      resistance of bacterial pathogens.
AB  - The biological activity (D-value determination) of eggshell membrane (ESM) was
      examined to determine the membrane components and mechanisms responsible for
      antibacterial activity. Biological and enzymatic activities (i.e., beta-N
      acetylglucosaminidase [beta-NAGase], lysozyme, and ovotransferrin) of ESM
      denatured with trypsin, lipases, or heat were compared with those of untreated
      ESM. Trypsin-treated ESM lost all biological activity (D-values at 54 degrees C
      were 5.12 and 5.38 min for immobilized and solubilized trypsin, respectively) but
      showed no significant loss of enzymatic activities. Treatments with porcine
      lipase and a lipase cocktail did not impact biological or enzymatic activities.
      Heat denaturation of ESM (at 80 and 100 degrees C for 15 min) resulted in
      significant decreases in biological activity (D-values of 3.99 and 4.43 min,
      respectively) and loss of beta-NAGase activity. Lysozyme and ovotransferrin
      activities remained but were significantly reduced. Purified ESM and hen egg
      white components (i.e., beta-NAGase, lysozyme, and ovotransferrin) were added to
      Salmonella Typhimurium suspensions (in 0.1% peptone water) at varying
      concentrations to evaluate their biological activity. D-values at 54 degrees C
      were 4.50 and 3.68 min for treatment with lysozyme or beta-NAGase alone,
      respectively, and 2.44 min for ovotransferrin but 1.47 min for a combination of
      all three components (similar to values for ESM). Exposure of Salmonella
      Typhimurium cells to a mixture of ovotransferrin, lysozyme, and beta-NAGase or
      ESM resulted in significant increases in extracellular concentrations of Ca2+,
      Mg2+, and K+. Transmission electron microscopic examination of Salmonella
      Typhimurium cells treated with a combination of ovotransferrin, lysozyme, and
      beta-NAGase revealed membrane disruption and cell lysis. The findings of this
      study demonstrate that ovotransferrin, lysozyme, and beta-NAGase are the primary
      components responsible for ESM antibacterial activity. The combination of these
      proteins and perhaps other ESM components interferes with interactions between
      bacterial lipopolysaccharides, sensitizing the outer bacterial membrane to the
      lethal affects of heat and possibly pressure and osmotic stressors.

PMID- 16629013
TI  - Detection of multiple antibiotic-resistant Salmonella enterica serovar
      Typhimurium DT104 by phage replication-competitive enzyme-linked immunosorbent
      assay.
AB  - A phage replication-competitive enzyme-linked immunosorbent assay (PR-cELISA) was
      developed for the detection of multiple antibiotic-resistant Salmonella
      Typhimurium DT104. In the PR-cELISA procedure, a phage, BP1, was inoculated into
      a log-phase bacterial culture at a ratio of 1:100. After a 3-h incubation of the
      mixture, BP1 replication was measured by cELISA based on the competitive binding
      between BP1 and biotinylated BP1 to Salmonella Typhimurium smooth
      lipopolysaccharide. Among the 84 Salmonella strains and 9 non-Salmonella strains
      that were tested by PR-cELISA, BP1 detected 39 of 40 Salmonella Typhimurium
      strains, 2 of 10 Salmonella non-Typhimurium somatic group B strains, and 5 of 18
      Salmonella somatic group D1 strains. With the addition of chloramphenicol to the
      culture medium, PR-cELISA detected all 27 multiple antibiotic-resistant
      Salmonella Typhimurium DT104 and none of the other Salmonella strains or non
      Salmonella strains tested. The results demonstrated that PR-cELISA has potential
      applications for the detection of multiple antibiotic-resistant Salmonella
      Typhimurium DT104.

PMID- 16629014
TI  - Comparison of prevalence, antimicrobial resistance, and occurrence of multidrug
      resistant Salmonella in antimicrobial-free and conventional pig production.
AB  - Conventional swine production evolved to routinely use antimicrobials, and common
      occurrence of antimicrobial-resistant Salmonella has been reported. There is a
      paucity of information on the antimicrobial resistance of Salmonella in swine
      production in the absence of antimicrobial selective pressure. Therefore, we
      compared the prevalence and antimicrobial resistance of Salmonella isolated from
      antimicrobial-free and conventional production systems. A total of 889 pigs and
      743 carcasses were sampled in the study. Salmonella prevalence was significantly
      higher among the antimicrobial-free systems (15.2%) than the conventional systems
      (4.2%) (odds ratio [OR] = 4.23; P < 0.05). Antimicrobial resistance was detected
      against 10 of the 12 antimicrobials tested. The highest frequency of resistance
      was found against tetracycline (80%), followed by streptomycin (43.4%) and
      sulfamethoxazole (36%). Frequency of resistance to most classes of antimicrobials
      (except tetracycline) was significantly higher among conventional farms than
      antimicrobial-free farms, with ORs ranging from 2.84 for chloramphenicol to 23.22
      for kanamycin at the on-farm level. A total of 28 antimicrobial resistance
      patterns were detected. A resistance pattern with streptomycin, sulfamethoxazole,
      and tetracycline (n = 130) was the most common multidrug resistance pattern.
      There was no significant difference in the proportion of isolates with this
      pattern between the conventional (19.5%) and the antimicrobial-free systems (18%)
      (OR = 1.8; P > 0.05). A pentaresistance pattern with ampicillin, chloramphenicol,
      streptomycin, sulfamethoxazole, and tetracycline was strongly associated with
      antimicrobial-free groups (OR = 5.4; P = 0.01). While showing the higher
      likelihood of finding antimicrobial resistance among conventional herds, this
      study also implies that specific multidrug-resistant strains may occur on
      antimicrobial-free farms. A longitudinal study with a representative sample size
      is needed to reach more conclusive results of the associations detected in this
      study.

PMID- 16629015
TI  - Comparison of antibiotic susceptibility profiles and molecular typing patterns of
      clinical and environmental Salmonella enterica serotype Newport.
AB  - The genus Salmonella is composed of more than 2,400 serotypes, many of which
      cause enteric diseases in humans and animals. Several Salmonella serotypes are
      multidrug resistant, and there is evidence of the clonal spread of these strains
      from animals to humans. Salmonella enterica serotype Newport is one of the
      serotypes that increasingly present a multidrug-resistant phenotype. Source
      tracking and antibiotic resistance testing are important considerations for
      identifying the outbreak strain. The first goal of this study was to examine the
      antibiotic susceptibility patterns of clinical and environmental Salmonella
      Newport isolates from various geographic locations and to compare the
      discriminatory ability of two DNA fingerprinting techniques. The second goal was
      to determine whether the antibiotic resistance profiles and typing patterns
      correlated. Thirty Salmonella Newport isolates, including environmental and human
      clinical strains, were subjected to pulsed-field gel electrophoresis (PFGE),
      ribotyping, and antibiotic susceptibility testing. Eighty percent of the isolates
      showed total or intermediate resistance to one or more drugs; 75% of the isolates
      were multidrug resistant. Ribotyping with the EcoRI enzyme and PFGE with the XbaI
      enzyme each divided the isolates into 14 groups. Cluster analysis based on
      antibiotic susceptibility patterns generated 23 profiles. The susceptible and
      resistant isolates were not differentiated on the basis of either of the
      molecular typing techniques. Hence, no correlation was observed between the
      antibiotic resistance profiles and the DNA subtyping patterns. In conclusion,
      ribotyping is as discriminatory as PFGE and, when used in combination with
      antibiotic resistance profiles, provides a powerful tool for the source tracking
      of Salmonella Newport.

PMID- 16629016
TI  - Quantification of Campylobacter on the surface and in the muscle of chicken legs
      at retail.
AB  - The objective of this study was to determine the prevalence and numbers of
      Campylobacter on the skin and in the muscle of chicken legs at retail to examine
      the external and internal contamination for an exposure assessment. Furthermore,
      the study assessed seasonal influence on Campylobacter contamination in chicken
      legs. Of the 140 examined skin samples, 66% were positive, and the internal
      contamination of 115 sampled chicken legs was 27%. The enumeration of
      Campylobacter on the surface of positive chicken legs revealed a median of 2.4
      log CFU/g of skin, and the quantification of Campylobacter in the muscle gave
      results mainly under the detection limit of the most-probable-number method (<0.3
      MPN Campylobacter per g). The external contamination was significantly higher
      than the internal. In both skin and muscle samples, Campylobacter jejuni had a
      much higher incidence than Campylobacter coli. However, with regard to the
      specification of Campylobacter on the surface of chicken legs, C. coli was
      isolated at higher colony counts than C. jejuni. During the 1-year study, two
      peaks of Campylobacter contamination occurred, one in the early springtime
      (February and March, 100 and 90%, respectively) and the second during the warmer
      months in the summer (July and August, both 90%). Furthermore, a positive
      correlation between prevalence and numbers of Campylobacter on chicken legs was
      observed.

PMID- 16629017
TI  - Reduction of Campylobacter jejuni on chicken wings by chemical treatments.
AB  - Eight chemicals, including glycerol monolaurate, hydrogen peroxide, acetic acid,
      lactic acid, sodium benzoate, sodium chlorate, sodium carbonate, and sodium
      hydroxide, were tested individually or in combination for their ability to
      inactivate Campylobacter jejuni at 4 degrees C in suspension. Results showed that
      treatment for up to 20 min with 0.01% glycerol monolaurate, 0.1% sodium benzoate,
      50 or 100 mM sodium chlorate, or 1% lactic acid did not substantially (< or = 0.5
      log CFU/ml) reduce C. jejuni populations but that 0.1 and 0.2% hydrogen peroxide
      for 20 min reduced C. jejuni populations by ca. 2.0 and 4.5 log CFU/ml,
      respectively. By contrast, treatments with 0.5, 1.0, 1.5, and 2.0% acetic acid,
      25, 50, and 100 mM sodium carbonate, and 0.05 and 0.1 N sodium hydroxide reduced
      C. jejuni populations by >5 log CFU/ml within 2 min. A combination of 0.5% acetic
      acid plus 0.05% potassium sorbate or 0.5% acetic acid plus 0.05% sodium benzoate
      reduced C. jejuni populations by >5 log CFU/ml within 1 min; however,
      substituting 0.5% lactic acid for 0.5% acetic acid was not effective, with a
      reduction of C. jejuni of <0.5 log CFU/ml. A combination of acidic calcium
      sulfate, lactic acid, ethanol, sodium dodecyl sulfate, and polypropylene glycol
      (ACS-LA) also reduced C. jejuni in suspension by >5 log CFU/ml within 1 min. All
      chemicals or chemical combinations for which there was a >5-log/ml reduction of
      C. jejuni in suspension were further evaluated for C. jejuni inactivation on
      chicken wings. Treatments at 4 degrees C of 2% acetic acid, 100 mM sodium
      carbonate, or 0.1 N sodium hydroxide for up to 45 s reduced C. jejuni populations
      by ca. 1.4, 1.6, or 3.5 log CFU/g, respectively. Treatment with ACS-LA at 4
      degrees C for 15 s reduced C. jejuni by >5 log CFU/g to an undetectable level.
      The ACS-LA treatment was highly effective in chilled water at killing C. jejuni
      on chicken and, if recycled, may be a useful treatment in chill water tanks for
      poultry processors to reduce campylobacters on poultry skin after slaughter.

PMID- 16629018
TI  - Adherence to and invasion of human intestinal epithelial cells by Campylobacter
      jejuni and Campylobacter coli isolates from retail meat products.
AB  - The abilities of 34 Campylobacter jejuni and 9 Campylobacter coli isolates
      recovered from retail meats to adhere to and invade human intestinal epithelial
      T84 cells were examined and compared with those of a well-characterized human
      clinical strain, C. jejuni 81-176, to better assess the pathogenic potential of
      these meat isolates. The meat isolates exhibited a wide range of adherence and
      invasion abilities; a few of the isolates adhered to and invaded T84 cells almost
      as well as did C. jejuni 81-176. There was a significant correlation between the
      adherence ability and the invasion ability of the Campylobacter isolates. The
      presence of eight putative virulence genes in these Campylobacter isolates that
      are potentially responsible for adherence and invasion or that encode cytolethal
      distending toxin was determined using PCR. All Campylobacter isolates possessed
      flaA, cadF, pldA, cdtA, cdtB, and cdtC, and most (91%) also contained the ciaB
      gene. However, the virB11 gene, carried by virulence plasmid pVir, was absent in
      almost all the Campylobacter isolates. Our findings indicated that C. jejuni and
      C. coli present in retail meat were diverse in their ability to adhere to and
      invade human intestinal epithelial cells and that the putative virulence genes
      were widespread among the Campylobacter isolates. Thus, despite of the presence
      of the putative virulence genes, only some but not all Campylobacter strains
      isolated from retail meat can effectively invade human intestinal epithelial
      cells in vitro.

PMID- 16629019
TI  - Amplified fragment length polymorphism, serotyping, and quinolone resistance of
      Campylobacter jejuni and Campylobacter coli strains from chicken-related samples
      and humans in Taiwan.
AB  - The high-resolution genotyping method of amplified fragment length polymorphism
      (AFLP) analysis was used to study the genetic relationships between Campylobacter
      jejuni isolates from chicken-related samples (n = 32) and humans (n = 27) as well
      as between Campylobacter coli isolates from chicken-related samples (n = 27) and
      humans (n = 5). These isolates were collected between 1994 and 2003 in Taiwan.
      All C. jejuni and C. coli isolates showed highly heterogeneous fingerprints. C.
      jejuni isolates were separated in two distinct genetic clusters (A and B) at 40%
      genetic similarity and 42 different AFLP types at 90% similarity. However, three
      clusters at 40% genetic similarity and 33 different AFLP types at 90% similarity
      were observed in C. coli isolates. These results showed that AFLP analysis could
      be used to identify individual isolates of two Campylobacter species. Among C.
      jejuni isolates, the predominant AFLP type 1 was observed in five (7.9%)
      isolates, and types 5 and 12 in four (6.3%) isolates each. Cluster B consisted of
      10 isolates, while the majority of isolates (n = 53) belonged to cluster A. In
      some AFLP types (1, 5, 12, 14 and 31), AFLP fingerprints of chicken-related
      isolates were closely related genetically to those of isolates from humans with
      gastroenteritis. The predominant serotypes in C. jejuni isolates were B:2 and
      Y:37. All isolates belonging to serotype O:19 grouped into one single AFLP type.
      Some chicken samples yielded multiple isolates of Campylobacter harboring
      simultaneously quinolone-resistant and quinolone-sensitive isolates attributed to
      the same species, or harboring C. jejuni and C. coli that have the
      characteristics of quinolone resistance.

PMID- 16629020
TI  - Inhibition of Salmonella enterica and Escherichia coli O157:H7 on roasted turkey
      by edible whey protein coatings incorporating the lactoperoxidase system.
AB  - The effects of whey protein isolate (WPI) coatings incorporating a
      lactoperoxidase system (LPOS) on the inhibition of Salmonella enterica and
      Escherichia coli O157:H7 on roasted turkey were studied by testing the initial
      inhibition as well as the inhibition during storage. The initial antimicrobial
      effects of WPI coatings incorporating LPOS (LPOS-WPI coatings) were examined with
      various inoculation levels and LPOS concentrations. LPOS-WPI coatings with 7 and
      4% of LPOS demonstrated initial 3- and 2-log CFU/g reductions of S. enterica and
      E. coli O157:H7, respectively. The antimicrobial effect was observed regardless
      of whether the turkey was inoculated before or after coating. Storage studies
      were conducted for 42 days at 4 and 10 degrees C with S. enterica (6.0 log CFU/g)
      or E. coli O157:H7 (5.6 log CFU/g)-inoculated sliced turkey. LPOS concentrations
      for the storage studies of S. enterica and E. coli O157:H7 were 5 and 3% (wt/wt),
      respectively, in the coating solution and in an LPOS solution for spreading. LPOS
      WPI coatings inhibited the growth of both S. enterica and E. coli O157:H7 in
      turkey at both 4 and 10 degrees C for 42 days. The inhibition was more pronounced
      when the coating was formed on the surface of the turkey prior to inoculation
      than when the coating was formed on the inoculated surface. More effective
      inhibition of S. enterica and E. coli O157:H7 was observed with the LPOS-WPI
      coatings than with the LPOS solution-spreading treatment. LPOS-WPI coatings also
      retarded the growth of total aerobes during storage.

PMID- 16629021
TI  - Validation of a traditional Italian-style salami manufacturing process for
      control of Salmonella and Listeria monocytogenes.
AB  - Italian-style salami batter (formulated with pork shoulder) was inoculated with
      ca. 7.0 log CFU/g of either Salmonella or Listeria monocytogenes. Salami links
      (55-mm cellulose casings) were fermented at 30 degrees C for 24, 40, or 72 h and
      then dried to target moisture/protein ratios (MPRs) of 1.9:1 or 1.4:1. Links were
      sampled after fermentation (24, 40, and 72 h) and after combined fermentation
      drying treatments (MPRs of 1.9:1 and 1.4:1 for all fermentation periods), and
      microbiological and proximate analyses were performed at each sampling. Pathogen
      populations were enumerated by direct plating on selective agar and by an injured
      cell recovery method. When enumerated by the injured-cell recovery method,
      Salmonella populations were reduced by 1.2 to 2.1 log CFU/g after fermentation
      alone (24 to 72 h) and by 2.4 to 3.4 log CFU/g when fermentation was followed by
      drying. Drying to an MPR of 1.4:1 was no more effective than drying to an MPR of
      1.9:1 (P > 0.05). When enumerated directly on selective media, Salmonella
      populations were reduced from 1.6 to 2.4 log CFU/g and from 3.6 to 4.5 log CFU/g
      for fermentation alone and fermentation followed by drying, respectively. L.
      monocytogenes populations were reduced by <1.0 log CFU/g following all
      fermentation and combined fermentation-drying treatments, regardless of the
      enumeration method. These results suggest that the Italian-style salami
      manufacturing process evaluated does not adequately reduce high pathogen loads.
      Processors may thus need to consider supplemental measures, such as raw material
      specifications and a final heating step, to enhance the lethality of the overall
      manufacturing process.

PMID- 16629022
TI  - Death of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in
      shelf-stable, dairy-based, pourable salad dressings.
AB  - The objectives of this study were to determine the death rates of Salmonella,
      Escherichia coli O157:H7, and Listeria monocytogenes in three commercially
      manufactured full-fat ranch salad dressings, three reduced-fat ranch salad
      dressings, two full-fat blue cheese salad dressings, and two reduced-fat blue
      cheese salad dressings and to affirm the expectation that these dressings do not
      support the growth of these pathogens. The respective initial pH values of the
      four types of shelf-stable, dairy-based, pourable dressings were 2.87 to 3.72,
      2.82 to 3.19, 3.08 to 3.87, and 2.83 to 3.49, respectively. Dressings were
      inoculated with low (2.4 to 2.5 log CFU/g) and high (5.3 to 5.9 log CFU/g)
      populations of separate five-strain mixtures of each pathogen and stored at 25
      degrees C for up to 15 days. Regardless of the initial inoculum population, all
      test pathogens rapidly died in all salad dressings. Salmonella was undetectable
      by enrichment (<1 CFU/25-ml sample in three replicate trials) in all salad
      dressings within 1 day, and E. coli O157:H7 and L. monocytogenes were reduced to
      undetectable levels by enrichment between 1 and 8 days and 2 and 8 days,
      respectively. E. coli O157:H7 was not detected in 4 of the 10 salad dressings
      stored for 2 or more days and 9 of the 10 dressings stored for 6 or more days
      after inoculation. L. monocytogenes was detected in 9 of the 10 salad dressings
      stored for 3 days but in only one dressing, by enrichment, at 6 days, indicating
      that it had the highest tolerance among the three pathogens to the acidic
      environment imposed by the dressings. Overall, the type of dressing (i.e., ranch
      versus blue cheese) and level of fat in the dressings did not have a marked
      effect on the rate of inactivation of pathogens. Total counts and populations of
      lactic acid bacteria and yeasts and molds remained low or undetectable (<1.0 log
      CFU/ml) throughout the 15-day storage period. Based on these observations, shelf
      stable, dairy-based, pourable ranch and blue cheese salad dressings manufactured
      by three companies and stored at 25 degrees C do not support the growth of
      Salmonella, E. coli O157:H7, and L. monocytogenes and should not be considered as
      potentially hazardous foods (time-temperature control for safety foods) as
      defined by the U.S. Food and Drug Administration Food Code.

PMID- 16629023
TI  - Prevalence and typing of Listeria monocytogenes in raw catfish fillets.
AB  - Raw channel catfish fillets collected from three processing plants during four
      time periods were tested for the presence of Listeria species. Listeria
      monocytogenes was the predominant Listeria species found in these catfish
      fillets, with 25 to 47% prevalence. Other Listeria species, such as L.
      welshimeri, L. innocua, L. ivanovii, L. grayi, and L. seeligeri, were also found.
      L. monocytogenes isolates were further fingerprinted by a repetitive element PCR.
      Forty distinctive electrophoretic types (ETs) and three genetic clusters were
      determined by Dice coefficient analysis and UPGMA (unweighted pair group method
      using arithmetic averages). Twenty of 40 ETs were represented by a single
      isolate, and the other 20 ETs were represented by 2 to 11 isolates. Thirty-five
      ETs, represented by 76 isolates, were found in processing plant A, B, or C and
      designated plant-specific types. The remaining five ETs, represented by 21
      isolates, were found in multiple plants and designated nonplant-specific types.
      In addition, 10 ETs from 52 isolates were found repeatedly during different
      seasons. Plant-specific and nonplant-specific L. monocytogenes coexisted in
      processed catfish fillets. Some isolates were persistently found in processed
      fillets, suggesting that either the current sanitation procedures used by these
      plants are inadequate or that these isolates originated from the natural habitats
      of the catfish. The results also suggest that the repetitive element PCR is a
      useful tool for differentiating L. monocytogenes subtypes and can be used for
      tracing the source of a contamination.

PMID- 16629024
TI  - Growth of Listeria monocytogenes in fresh-cut coconut as affected by storage
      conditions and inoculum size.
AB  - In this study, the effects of packaging atmosphere (air and modified atmosphere,
      65% N2, 30% CO2, and 5% O2), temperature (2, 4, 8, and 12 degrees C) and inoculum
      size (low inoculum, 102 CFU/g; high inoculum, 5 x 10(5) CFU/g) on the growth of
      Listeria monocytogenes in minimally processed coconut were investigated. Growth
      data were fitted to the Gompertz equation, and the sanitary risk time (the time,
      in days, necessary to observe an increase of 2 log CFU/g in the level of the
      pathogen) was also calculated. At a higher inoculum level, the health risk was
      more marked; moreover, as shown by parameter A of the Gompertz equation (maximum
      increase of cell load data), the sanitary risk time seemed not to be influenced
      by temperature or by atmosphere type. At a low inoculum level in the air-stored
      product, the sanitary risk time was strongly influenced by temperature, and a
      modified atmosphere caused a significant increase in the maximum cell load
      reached in the stationary phase. The results show that L. monocytogenes not only
      survives but is able to proliferate on fresh-cut coconut stored in air as well as
      in a modified atmosphere, even at a very low temperature (2 degrees C); moreover,
      the presence of a high cell load can lead to a health risk because this pathogen
      can grow to risk level during the shelf life of the product.

PMID- 16629025
TI  - Formation of biofilm at different nutrient levels by various genotypes of
      Listeria monocytogenes.
AB  - Strains of Listeria monocytogenes differ in their ability to form biofilms. The
      objectives of this study were to determine whether genetically related strains
      have similar biofilm-forming capacities and what effect nutrient concentration
      has on the ability of different strains to produce biofilms. Biofilms of 30
      strains of L. monocytogenes, obtained from a variety of sources were grown on
      stainless steel in tryptic soy broth (TSB) or in a 1:10 dilution of TSB (DTSB)
      for 24 h at 32 degrees C. The amount of biofilm formed was determined with image
      analysis after cells were stained with bisBenzimide H 33258 (Hoechst 33258). The
      strains were genetically subtyped by repetitive element sequence-based PCR (rep
      PCR) with the primer set rep-PRODt and rep-PROG5. Data were analyzed with an
      analysis of variance and Duncan's multiple range test. Eleven strains produced
      the same amount of biofilm in both media. Fourteen strains produced more biofilm
      in TSB than in DTSB. Five strains produced more biofilm in DTSB than in TSB.
      Serotype 4b strains produced more biofilm in TSB than did serotype 1/2a strains,
      whereas serotype 1/2a strains produced more biofilm in DTSB than did serotype 4b
      strains. Growth in DTSB resulted in decreased biofilm accumulation for serotype
      4b strains. There was no correlation between genetic subtype and the amount of
      biofilm accumulation. These results indicate that strains of serotype 1/2a and
      serotype 4b differ in the regulation of their biofilm phenotype. The poor biofilm
      accumulation of serotype 4b isolates when grown in DTSB could be a factor in the
      predominance of serogroup 1/2 strains in food processing plants, where nutrients
      may be limited.

PMID- 16629026
TI  - Molecular typing to trace Listeria monocytogenes isolated from cold-smoked fish
      to a contamination source in a processing plant.
AB  - In this study, Listeria monocytogenes contamination in a cold-smoked fish
      processing plant in Osaka, Japan, was examined from 2002 to 2004. A total of 430
      samples were collected and divided into five categories: raw fish, materials
      during processing, processing equipment, environment, and finished products. A
      total of 59 finished products were examined throughout this study. L.
      monocytogenes was isolated from four of these samples during summer and autumn
      but was not found during winter or spring. During the warmer seasons, L.
      monocytogenes was more prevalent on processing equipment, especially slicing
      machines (8 of 54 samples in summer and autumn versus 1 of 50 samples in winter
      and spring). L. monocytogenes was not detected on whole skins removed from 23
      frozen raw fish. L. monocytogenes strains isolated from 56 samples were
      characterized by serotyping, pulsed-field gel electrophoresis, and three PCR
      based methods. Seventy-seven L. monocytogenes strains were recognized as
      contaminants of the samples: 2 distinguishable strains were identified in each of
      13 samples, 3 strains were identified in 2 samples, 5 strains were identified in
      1 sample, and the other 40 strains were identified in 40 samples. Combining the
      results from these techniques, 77 strains were classified into 13 different
      types. Three of these types prevailed throughout the plant, and two of the three
      were also isolated from final products. The DNA subtype found in the product was
      also found on the slicing machines. Our findings suggest that the slicing
      machines at this plant were the source of the product contamination. Implementing
      an appropriate cleaning regime for the slicing machines was effective in
      preventing contamination.

PMID- 16629027
TI  - Comparison of Listeria monocytogenes virulence in a mouse model.
AB  - Listeriosis results from exposure to the foodborne pathogen Listeria
      monocytogenes. Although many different strains of L. monocytogenes are isolated
      from food, no definitive tests currently predict which isolates are most
      virulent. The objectives of this study were to address two major data gaps for
      risk assessors, variability among L. monocytogenes strains in pathogenicity and
      virulence. Strains used in our monkey clinical trial or additional food isolates
      were evaluated for their virulence and infectivity in mice. All strains were
      equally pathogenic to immunocompromised mice, causing deaths to 50% of the
      population 3 days after exposure to doses ranging from 2 to 3 log CFU. Doses
      resulting in 50% deaths on the fifth day after administration were 1 to 2 log
      lower than those on the third day, indicating that the full course of
      pathogenicity exceeds the 3-day endpoint in immunocompromised mice. Three strains
      were chosen for further testing for their virulence and infectivity in liver and
      spleen in normal (immunocompetent) mice. Virulence was not significantly
      different (P > 0.05) among the three strains, all resulting in deaths to 50% of
      mice at 5 to 7 log CFU by 5 days after administration. All strains were equally
      infective in liver or spleen, with higher numbers of L. monocytogenes directly
      correlated with higher doses of administration. In addition, there was no
      preference of organs by any strains. The lack of strain differences may reflect
      the limitation of the mouse model and suggests the importance of using various
      models to evaluate the pathogenicity and virulence of L. monocytogenes strains.

PMID- 16629028
TI  - Influence of type of food on the kinetics and overall production of Bacillus
      cereus emetic toxin.
AB  - Potato puree and penne pasta were inoculated with cereulide producing B. cereus
      5964a and B. cereus NS117. Static incubation at 28 degrees C proved these two
      foods to be a better substrate for higher cereulide production (4,080 ng/g in
      puree and 3,200 ng/g in penne were produced by B. cereus 5964a during 48 h of
      incubation) compared with boiled rice (2,000 ng/g). This difference occurred
      despite B. cereus counts of more than 10(8) CFU/g in all three products. Aeration
      of cultures had a negative effect on cereulide production, causing concentrations
      more than 10-fold lower than in some statically incubated samples. Cereulide
      production remained undetectable in shaken milk, whereas it reached 1,140 ng/ml
      in statically incubated milk. At 12 and 22 degrees C, presence of background
      flora was also a determinative factor. A total B. cereus count of more than 106
      CFU/ml did not necessarily lead to uniform cereulide production and was also
      dependent on the B. cereus strain involved. In this study, we confirm that a
      number of factors play a crucial role in the determination of the extent to
      which, if at all, cereulide will be produced. Among those, type of the food,
      temperature, pH, and whether additional aeration (via incubation on an orbital
      shaker) is induced had an important role. An important effect was also induced by
      the cereulide-producing strain involved.

PMID- 16629029
TI  - Combined pressure-thermal inactivation kinetics of Bacillus amyloliquefaciens
      spores in egg patty mince.
AB  - Bacillus amyloliquefaciens is a potential surrogate for Clostridium botulinum in
      validation studies involving bacterial spore inactivation by pressure-assisted
      thermal processing. Spores of B. amyloliquefaciens Fad 82 were inoculated into
      egg patty mince (approximately 1.4 x 10(8) spores per g), and the product was
      treated with combinations of pressure (0.1 to 700 MPa) and heat (95 to 121
      degrees C) in a custom-made high-pressure kinetic tester. The values for the
      inactivation kinetic parameter (D), temperature coefficient (zT), and pressure
      coefficient (zP) were determined with a linear model. Inactivation parameters
      from the nonlinear Weibull model also were estimated. An increase in process
      pressure decreased the D-value at 95, 105, and 110 degrees C; however, at 121
      degrees C the contribution of pressure to spore lethality was less pronounced.
      The zP-value increased from 170 MPa at 95 degrees C to 332 MPa at 121 degrees C,
      suggesting that B. amyloliquefaciens spores became less sensitive to pressure
      changes at higher temperatures. Similarly, the zT-value increased from 8.2
      degrees C at 0.1 MPa to 26.8 degrees C at 700 MPa, indicating that at elevated
      pressures, the spores were less sensitive to changes in temperature. The
      nonlinear Weibull model parameter b increased with increasing pressure or
      temperature and was inversely related to the D-value. Pressure-assisted thermal
      processing is a potential alternative to thermal processing for producing shelf
      stable egg products.

PMID- 16629030
TI  - Antimicrobial effectiveness of lysozyme immobilized on polyvinylalcohol-based
      film against Alicyclobacillus acidoterrestris.
AB  - In this study, the effectiveness of an active polyvinylalcohol-based film against
      Alicyclobacillus acidoterrestris was assessed. The active film was fabricated by
      immobilizing an active compound on the surface of a polymeric matrix and then
      tested by putting the film in contact with a medium that had been inoculated with
      microbial cells. Microbiological tests showed that the film was antimicrobial
      against both a single strain and a culture cocktail of A. acidoterrestris, at 44
      degrees C. By monitoring the viable cell concentration under three different
      packaging conditions, it was possible to demonstrate that the active film was
      equally effective against both the single strain and the culture cocktail and
      that it maintained this efficacy at various medium volumes. The same microbial
      tests were also conducted on viable spores of the investigated microorganism,
      inoculated both into a laboratory medium and apple juice. The results indicate
      that these viable spores were better inhibited than cells by the active film in
      both investigated media.

PMID- 16629031
TI  - Immobilization of lysozyme on polyvinylalcohol films for active packaging
      applications.
AB  - A new technique for the immobilization of lysozyme onto the surface of
      polyvinylalcohol films is presented. The active compound was sprayed along with a
      suitable bonding agent onto the surface of the cross-linked polymeric matrix.
      Active compound release tests determined the amount of lysozyme immobilized on
      the film surface. With the use of Micrococcus lysodeikticus, the antimicrobial
      activity of the films was determined and the results correlated with the amount
      of immobilized lysozyme. This new technique was effective for immobilizing the
      enzyme, and the developed films were active against the test microorganism.
      Results were compared with those obtained with a different immobilizing
      technique, in which the active compound was bound into the bulk of the polymeric
      film. As expected, the surface-immobilized lysozyme films have a higher
      antimicrobial activity than bulk-bound films.

PMID- 16629032
TI  - Bifidobacterium species isolated from animal feces and from beef and pork meat.
AB  - Bifidobacteria were isolated from 122 of 145 samples of animal feces (from
      cattle, swine, sheep, goats, horses, rabbits, chickens, geese, and pigeons) from
      farms in France and Austria and from 92 of 955 production and processing chain
      samples of beef and pork (obtained at slaughter, cutting, and retail). Bacterial
      strains were identified to species by phenotypic numerical classification based
      on API 50CH and ID 32A tests and DNA-DNA hybridization. Bifidobacterium
      pseudolongum was present in 81% (99 of 122 samples) of all Bifidobacterium
      positive fecal samples and predominated in samples from all animal species except
      those from swine from Austria. In these Austrian swine samples, the majority of
      strains were identified as Bifidobacterium thermophilum (78%), followed by B.
      pseudolongum (48%). The distribution of B. thermophilum and B. pseudolongum
      differed significantly between Austrian swine and cattle samples such as those
      collected along beef and pork production and processing chains. Bifidobacterium
      animalis was isolated from swine feces, and Bifidobacterium ruminantium was
      isolated from cow dung. Six fecal isolates (from cattle, swine, rabbits, goats,
      and horses) were identified as belonging to Bifidobacterium species of
      predominantly human origin: B. adolescentis, B. bifidum, and B. catenulatum. Only
      one other species, Bifidobacterium choerinum, was detected with low frequency in
      a pork processing chain. B. pseudolongum subsp. pseudolongum was predominant in
      pig feces, whereas B. pseudolongum subsp. globosum was predominant in feces from
      other animal species. Four strains closely related to both subspecies (58 to 61%
      DNA reassociation) formed a distinct genomic group. PCR techniques, which are
      more rapid and sensitive than culture-based methods, could be used to detect
      directly B. pseudolongum and B. thermophilum as indicators of fecal contamination
      along the meat processing chain.

PMID- 16629033
TI  - Growth of Mycobacterium avium subsp. paratuberculosis in the presence of
      hexadecylpyridinium chloride, natamycin, and vancomycin.
AB  - A design-of-experiments approach was used to examine the effect of
      hexadecylpyridinium chloride (HPC), alone or in combination with the antibiotics
      vancomycin and natamycin, on the growth of Mycobacterium avium subsp.
      paratuberculosis (MAP). At concentrations above 74.4 microg/ml, HPC had a highly
      significant detrimental effect on the growth of MAP, whereas natamycin at 10.8
      and 21.6 microg/ml and vancomycin at 5.2 and 10.4 microg/ml did not have such an
      effect. Titration of the amount of HPC tolerated by MAP indicated that growth can
      occur in the presence of 24.8 microg/ml or lower. Processing of bovine fecal
      specimens indicated that reducing the concentration of HPC from 32.22 to 1.07
      mg/ml during decontamination may improve detection when cultures are grown on
      solid medium but not when cultures are grown in liquid medium. Further
      investigation into optimizing HPC concentration during processing of fecal
      samples is warranted. Natamycin, in conjunction with vancomycin, may be useful
      for controlling fungal contamination during isolation of MAP from fecal samples.

PMID- 16629034
TI  - Spatial distribution of ochratoxin A in vineyard and sampling design to assess
      must contamination.
AB  - The aim of this work was to study the spatial variability of ochratoxin A (OTA)
      in vineyards and to define a reliable sampling protocol for bunches in order to
      assess OTA content before harvesting. In 2002, two vineyards with 'Negroamaro'
      and 'Sangiovese' grape varieties were chosen in Southern Italy. The same sampling
      design was applied to both vineyards. Ten plants were collected from the X-shaped
      path of the whole vineyard (plants 1 through 10) and 10 plants from the two
      central cross-perpendicular lines (plants 11 through 20). Bunches harvested from
      plants 1 through 10 were numbered progressively, weighed, and crushed separately,
      and bunches obtained from plants 11 through 20 were crushed plant by plant.
      Juices obtained were analyzed for OTA content by high-performance liquid
      chromatography. Then, a simulated approach for sampling was applied, following
      randomized and systematic designs. High and random variability was observed in
      OTA content both among bunches and among plants in the two vineyards, independent
      of contamination level. Simulated sampling design markedly influenced the
      assessment of must contamination. The best results were obtained when sampling
      involved one bunch per plant, in a predefined position, from at least 10 plants.
      Estimated means, obtained with different sampling designs, did not differ
      significantly from calculated mean OTA content. If the true contamination in a
      vineyard is 2 microg kg(-1), the limit fixed in Europe for OTA content in must
      and wine, the range of OTA content assessed sampling one bunch in the central
      position of 10 plants should lie between 2.9 and 1.4. The accuracy could be
      considered acceptable.

PMID- 16629035
TI  - Application of quantitative real-time PCR in the detection of prion-protein gene
      species-specific DNA sequences in animal meals and feedstuffs.
AB  - This study describes a method for quantitative and species-specific detection of
      animal DNA from different species (cattle, sheep, goat, swine, and chicken) in
      animal feed and feed ingredients, including fish meals. A quantitative real-time
      PCR approach was carried out to characterize species-specific sequences based on
      the amplification of prion-protein sequence. Prion-protein species-specific
      primers and TaqMan probes were designed, and amplification protocols were
      optimized in order to discriminate the different species with short PCR
      amplicons. The real-time quantitative PCR approach was also compared to
      conventional species-specific PCR assays. The real-time quantitative assay
      allowed the detection of 10 pg of ruminant, swine, and poultry DNA extracted from
      meat samples processed at 130 degrees C for 40 min, 200 kPa. The origin of
      analyzed animal meals was characterized by the quantitative estimation of
      ruminant, swine, and poultry DNA. The TaqMan assay was used to quantify ruminant
      DNA in feedstuffs with 0.1% of meat and bone meal. In conclusion, the proposed
      molecular approach allowed the detection of species-specific DNA in animal meals
      and feedstuffs.

PMID- 16629036
TI  - Formation of histamine and biogenic amines in cold-smoked tuna: an investigation
      of psychrotolerant bacteria from samples implicated in cases of histamine fish
      poisoning.
AB  - Two outbreaks and a single case of histamine fish poisoning associated with cold
      smoked tuna (CST) were reported in Denmark during 2004. The bacteria most likely
      responsible for histamine formation in CST implicated in histamine fish poisoning
      was identified for the first time in this study. Product characteristics and
      profiles of biogenic amines in the implicated products were also recorded. In the
      single poisoning case, psychrotolerant Morganella morganii-like bacteria most
      likely was responsible for the histamine production in CST with 2.2% +/- 0.6%
      NaCl in the water phase (WPS). In outbreak 1, Photobacterium phosphoreum most
      likely formed the histamine in CST with 1.3% +/- 0.1% WPS. In outbreak 2, which
      involved 10 persons, the bacteria responsible for histamine formation could not
      be determined. The measured concentrations of WPS were very low compared with
      those of randomly collected commercial samples of CST and cold-smoked blue marlin
      (4.1 to 12.7% WPS). Challenge tests at 5 degrees C with psychrotolerant M.
      morganii and P. phosphoreum in CST with 4.4% WPS revealed growth and toxic
      histamine formation by the psychrotolerant M. morganii-like bacteria but not by
      P. phosphoreum. In a storage trial with naturally contaminated CST containing
      6.9% WPS, lactic acid bacteria dominated the microbiota, and no significant
      histamine formation was observed during the shelf life of about 40 days at 5
      degrees C and of about 16 days at 10 degrees C. To prevent toxic histamine
      formation, CST should be produced with >5% WPS and distributed with a declared 5
      degrees C shelf life of 3 to 4 weeks or less.

PMID- 16629037
TI  - Effect of immersion chilling of broiler chicken carcasses in monochloramine on
      lipid oxidation and halogenated residual compound formation.
AB  - This study was conducted to evaluate the effect of immersion chilling of broiler
      chicken carcasses in tap water (TAP) or TAP containing 50 ppm of monochloramine
      (MON) with respect to chloroform formation, total chlorine content, 2
      thiobarbituric acid (TBA) values, and fatty acid profiles. Ten broiler chicken
      carcasses were chilled in TAP or MON for 6 h. After exposure, the carcasses were
      removed and cut in half along the median plane into right and left halves. After
      roasting the left halves, samples of the breast, thigh, and skin (with fat) were
      collected, subjected to fatty acid profiling, and assayed for chloroform, total
      chlorine, and TBA. The uncooked right halves of each carcass were stored at 4
      degrees C for 10 days and then roasted. After roasting these right halves,
      samples of breast, thigh, and skin (with fat) were collected from each carcass
      half, subjected to fatty acid profiling, and assayed for chloroform, total
      chlorine, and TBA. There were no statistical differences between TAP- and MON
      treated fresh or stored products with regard to chloroform levels, total chlorine
      content, TBA values, or fatty acid profiles.

PMID- 16629038
TI  - Combination of hot-water surface pasteurization of whole fruit and low-dose gamma
      irradiation of fresh-cut cantaloupe.
AB  - Improvements in methods for disinfecting fresh-cut cantaloupe could reduce
      spoilage losses and reduce the risk of foodborne illness from human pathogen
      contamination. The objective of this study was to investigate the feasibility of
      using hot-water treatment in combination with low-dose irradiation to reduce
      native microbial populations while maintaining the quality of fresh-cut
      cantaloupe. Whole cantaloupes were washed in tap water at 20 or 76 degrees C for
      3 min. Fresh-cut cantaloupe cubes, prepared from the washed fruit, were then
      packaged in clamshell containers, and half the samples were exposed to 0.5 kGy of
      gamma radiation. Native microflora populations and sensory qualities were
      evaluated during the subsequent 7 days of storage at 4 degrees C. The hot-water
      surface pasteurization reduced the microflora population by 3.3 log on the
      surface of whole fruits, resulting in a lower microbial load on the fresh-cut
      cubes compared with cubes cut from fruit treated with cold water. Irradiation of
      cubes prepared from untreated fruit to an absorbed dose of 0.5 kGy achieved a low
      microbial load similar to that of cubes prepared from hot-water-treated fruit.
      The combination of the two treatments was able to further reduce the microflora
      population. During storage, the headspace atmosphere of the packages was not
      significantly influenced by any of the treatments. Color, titratable acidity, pH,
      ascorbic acid, firmness, and drip loss were not consistently affected by
      treatment with irradiation, hot water, or the combination of the two. Cubes
      prepared from hot-water-treated whole fruit had slightly lower soluble solids
      content. The combination of hot-water pasteurization of whole cantaloupe and low
      dose irradiation of packaged fresh-cut melon can reduce the population of native
      microflora while maintaining the quality of this product.

PMID- 16629039
TI  - Detection, occurrence, and characterization of Escherichia coli O157:H7 from raw
      ewe's milk in Spain.
AB  - A study was carried out in the Castilla y Leon region of Spain to investigate the
      presence of Escherichia coli O157:H7 in raw ewe's milk samples collected from
      several cheese factories during 1 year. All specimens were examined for E. coli
      O157:H7 by selective enrichment at 41.5 +/- 1.0 degrees C, after both 6 and 22 h
      of incubation, and then immunomagnetically separated and plated on cefixime
      potassium tellurite-sorbitol MacConkey agar. No growth was obtained in the
      enrichment broth after a 6-h incubation. Presumptive colonies obtained after 22 h
      of incubation were screened by a multiplex PCR assay for the presence of rfbO157
      and fliCH7 genes. Of all the ewe's milk samples studied, three were positive for
      E. coli O157:H7. The E. coli O157:H7 strains that were positive for the rfbO157
      and fliCH7 genes were then analyzed by multiplex PCR for the presence of
      virulence genes (stx1, stx2, ehxA, and eaeA). All E. coli O157:H7 isolates were
      Shiga toxigenic and harbored additional genes related to virulence (ehxA and
      eaeA). The predominant Stx toxin type was stx2. These results demonstrate that
      raw ewe's milk used in cheesemaking may be sporadically contaminated with E. coli
      O157:H7 strains that are potentially pathogenic for humans.

PMID- 16629040
TI  - Salmonella enterica in superficial cervical (prescapular) and ileocecal lymph
      nodes of slaughtered pigs.
AB  - Because certain lymph nodes may be incorporated in food products, the presence of
      Salmonella enterica in these tissues could pose a food safety risk. We designed
      this two-part study to assess the prevalence of Salmonella in prescapular lymph
      nodes from normal slaughtered swine. Prescapular lymph nodes were collected from
      300 systematically selected pigs in study 1 and, in study 2, from 75 pigs
      distributed among 10 herds. For study 2, pooled bacterial cultures were also
      completed on ileocecal lymph nodes, combining tissue from five pigs per pool (n =
      60 pools). No Salmonella was detected in study 1 among prescapular lymph nodes
      (95% confidence interval, 0.0 to 1.16%). Salmonella was not detected in 75
      prescapular lymph nodes from study 2, although Salmonella was detected in 5 of 10
      herds in ileocecal lymph nodes. We conclude that prescapular lymph nodes posed a
      limited food safety risk in this population of pigs.

PMID- 16629041
TI  - Three-year surveillance program examining the prevalence of Campylobacter and
      Salmonella in whole retail raw chicken.
AB  - A 36-month study of Campylobacter and Salmonella in retail raw whole chicken was
      carried out to measure baseline rates at the retail level, establish seasonality,
      and observe changes in rates over time. In total, 2,228 samples were taken
      between November 2001 and December 2004. The Campylobacter rate was unchanged
      over the 3 years of the study, but the Salmonella rates declined significantly
      between 2001 and 2004. There was also some seasonality in Campylobacter rates in
      fresh samples. The overall conclusion from the study was that the Salmonella rate
      in raw chicken available to consumers in Wales fell significantly between 2001
      and 2004, while the Campylobacter rate remained unchanged and is still by far the
      greater problem.

PMID- 16629042
TI  - Metronidazole resistance in Campylobacter jejuni from poultry meat.
AB  - The occurrence of metronidazole resistance was investigated among Campylobacter
      jejuni in raw poultry meat collected from supermarkets. MICs were determined by
      the agar dilution procedure in the testing range of 3 to 60 microg/ml
      metronidazole. The MICs showed a bimodal distribution with a significant
      proportion of metronidazole-resistant isolates among C. jejuni from raw broiler
      and turkey meat. Metronidazole resistance occurred most frequently among turkey
      meat isolates (P < 0.005). This is the first report of foodborne bacteria
      carrying metronidazole resistance.

PMID- 16629043
TI  - Effect of high-pressure processing on strains of Enterobacter sakazakii.
AB  - Four strains of Enterobacter sakazakii were inoculated into tryptic soy broth and
      reconstituted powdered infant formula and exposed to high-pressure processing.
      Pressures of 200, 400, and 600 MPa were used for each medium for 1 min. E.
      sakazakii was reduced by more than 6 log (strains A and B) in both media at 600
      MPa. Strain B was significantly (P < or = 0.05) more pressure resistant than the
      other strains, with just more than a 3-log reduction at 600 MPa in both media.
      The reconstituted infant formula has a significant (P < or = 0.05) protective
      effect for certain strains and pressures (strain B at 400 MPa and strain D at 400
      and 600 MPa). Differences in log reductions between media (milk and broth) were
      also observed for certain strains and specific pressures (strain B at 400 MPa and
      strain D at 400 and 600 MPa; P < or = 0.05). This research showed that E.
      sakazakii, when present in reconstituted powdered infant formula, can be
      submitted to high-pressure processing (600 MPa for 1 min) and achieve log
      reductions ranging from 3 to 6.84, depending on the strain.

PMID- 16629044
TI  - Prevalence and concentration of Listeria monocytogenes in sliced ready-to-eat
      meat products in the Hellenic retail market.
AB  - The aim of this work was to estimate the prevalence and concentration of Listeria
      monocytogenes in packaged precut (slices or cubes) ready-to-eat (RTE) meat
      products available in the Hellenic retail market. Samples of these RTE meat
      products (n = 209) were taken from local supermarkets during a 3-month period and
      analyzed for the presence of L. monocytogenes with an automated enzymatic
      qualitative immunoassay followed by biochemical confirmation of positive results.
      The concentration of the pathogen in the positive samples was also determined.
      Seventeen samples (8.1%) were positive for L. monocytogenes. Eight (47.1%) of
      these 17 samples were from the same manufacturer; 36.4% of the products tested
      from this manufacturer were positive for L. monocytogenes. When bacon samples
      were not considered, the estimated prevalence of L. monocytogenes in sliced RTE
      meat products was much lower (3.1%). The L. monocytogenes populations in all
      positive samples were low, < or = 10 CFU/g. In 64.7% of the L. monocytogenes
      positive samples, other Listeria species, including L. innocua and L. welshimeri,
      were also present at <10 to 690 CFU/g. These results indicate that L.
      monocytogenes is present in low numbers but is in a considerable proportion of
      the packaged precut RTE meat products that are sold in the Hellenic retail
      market. Cooked ham and bacon cut in cubes were the sample types most often
      contaminated with L. monocytogenes. The higher level of handling (e.g., cutting)
      associated with these products may further increase the risk of contamination
      with L. monocytogenes.

PMID- 16629045
TI  - Effect of high-barrier packaging films with different oxygen transmission rates
      on the growth of Lactobacillus sp. on meat fillets.
AB  - The goal of this study was to determine the combined effect of (i) the oxygen
      transmission rate (OTR) of packaging film, often called oxygen film permeability
      or film permeability and (ii) temperature on the growth rate of the main
      prevailing organism, Lactobacillus sp., in 100% CO2-packed sterile meat fillets.
      Multifactorial experiments were designed to study the effect of OTR and
      temperature (0, 5, 8, and 10 degrees C) on the growth rate of Lactobacillus sp.
      inoculated on sterile meat fillets under 100% CO2 and aerobic conditions. The
      packaging conditions (air or 100% CO2) and the film OTR significantly affected
      the growth rate of Lactobacillus sp. only at temperatures higher than 0 degrees
      C. Low-permeable films with different OTRs did not affect the final population of
      the bacterium, but the growth rate was significantly changed. The correlation of
      an ephemeral microbial association with a low spoilage potential (e.g., lactic
      acid bacteria) or their growth retardation cannot always be assumed unless other
      determinants (e.g., OTR) of equal importance are taken into account. The present
      study provides information that can be of benefit to industry and the consumer.

PMID- 16629046
TI  - Cooking mussels (Mytilus galloprovincialis) by steam does not destroy the
      infectivity of Cryptosporidium parvum.
AB  - The consumption of shellfish has increased considerably worldwide, with an
      associated increase in foodborne illnesses. Among the bivalves, the mussels are
      usually cooked by steam, which constitutes a typical dish in several regions. In
      this article, we demonstrate that this preparation is not sufficient to destroy
      completely the infectivity of Cryptosporidium parvum. Oocysts recovered from
      experimentally contaminated mussels (Mytilus galloprovincialis) were infectious
      to neonatal mice after cooking. Although, to date, no official cases of
      cryptosporidiosis linked to shellfish consumption have been reported, we
      recommend that people with reduced immunity avoid this type of food because they
      are at high risk of being infected with Cryptosporidium spp. after eating raw or
      undercooked contaminated bivalves.

PMID- 16629047
TI  - Interactions of nisin with glutathione in a model protein system and meat.
AB  - Loss of nisin activity in meat has been ascribed, in part, to the formation of a
      nisin-glutathione adduct. Activity is lost more quickly in raw meat than in
      cooked meat, and this has been taken as evidence that the reaction is enzyme
      mediated. Formation of the nisin-glutathione adduct has been confirmed but is
      shown not to be enzyme mediated. Retention of activity in cooked meat is shown to
      be due to the loss of free sulfhydryl groups during cooking as a result of the
      reaction of glutathione with proteins and not a result of the inactivation of
      endogenous enzymes. Microbial enzymes do not appear to play a role, as similar
      losses are seen in raw and cooked meat extracts, both of which contained
      undetectable levels of microorganisms.

PMID- 16629048
TI  - Inactivation of foodborne viruses of significance by high pressure and other
      processes.
AB  - The overall safety of a food product is an important component in the mix of
      considerations for processing, distribution, and sale. With constant commercial
      demand for superior food products to sustain consumer interest, nonthermal
      processing technologies have drawn considerable attention for their ability to
      assist development of new products with improved quality attributes for the
      marketplace. This review focuses primarily on the nonthermal processing
      technology high-pressure processing (HPP) and examines current status of its use
      in the control and elimination of pathogenic human viruses in food products.
      There is particular emphasis on noroviruses and hepatitis A virus with regard to
      the consumption of raw oysters, because noroviruses and hepatitis A virus are the
      two predominant types of viruses that cause foodborne illness. Also, application
      of HPP to whole-shell oysters carries multiple benefits that increase the
      popularity of HPP usage for these foods. Viruses have demonstrated a wide range
      of sensitivities in response to high hydrostatic pressure. Viral inactivation by
      pressure has not always been predictable based on nomenclature and morphology of
      the virus. Studies have been complicated in part from the inherent difficulties
      of working with human infectious viruses. Consequently, continued study of viral
      inactivation by HPP is warranted.

PMID- 16629049
TI  - The search for a cure for Duchenne muscular dystrophy (DMD).

PMID- 16629050
TI  - What do animal models have to tell us regarding Duchenne muscular dystrophy?
AB  - Animal models of DMD have played, and will continue to play, a key role in the
      understanding of the pathogenesis and treatment of Duchenne muscular dystrophy
      (DMD). The mdx mouse and GRMD dog are spontaneous dystrophin deficient mutants
      and have been the most widely used models to date. A number of other murine
      models have been created by exposure to mutagens or genetic manipulation. The
      animal models have allowed the development of a number of promising experimental
      therapeutic approaches to DMD that are now entering clinical trial, the majority
      of which would not have been developed without their use. However, there has been
      much debate about the merits of the different animal models, which will only be
      finally clear as we learn from the initial human clinical trials.

PMID- 16629051
TI  - Stem cells to treat muscular dystrophies.
AB  - Stem cells, capable of giving rise to both differentiated skeletal muscle and to
      more stem cells, would be ideal for treating chronic myopathies such as Duchenne
      Muscular Dystrophy. However, although satellite cells have been shown to be
      functional muscle stem cells in animal models, other muscle or non-muscle stem
      cells are far less capable of contributing to skeletal muscle regeneration. This
      review discusses recent work on stem cell contribution to skeletal muscle
      regeneration and highlights the problems to be overcome before stem cell
      treatment of muscle diseases may become a possibility.

PMID- 16629052
TI  - Gene therapy for Duchenne muscular dystrophy: AAV leads the way.
AB  - Over the past decade, adeno-associated virus (AAV) has become an extremely
      promising vector for gene therapy of many genetic disorders. This review
      summarizes the specific challenges that must be overcome to apply AAV gene
      therapy to Duchenne muscular dystrophy. Many of these challenges have been met
      successfully in animal studies, but further work is needed to translate these
      results into an effective clinical treatment.

PMID- 16629053
TI  - Oligonucleotide-mediated gene editing for neuromuscular disorders.
AB  - In the last decade, outstanding progress has been made in the development of new
      approaches to treat neuromuscular disorders and in particular Duchenne muscular
      dystrophy (DMD). The use of oligonucleotides to induce single base pair
      alterations in the dystrophin gene and restore gene expression in skeletal muscle
      has proven to be a feasible alternative approach to dystrophin gene replacement.
      Oligonucleotide-mediated gene editing for dystrophin has the potential to treat
      the disorder permanently and effectively. Many hurdles however still need to be
      overcome before this technology can enter into a clinical setting. Understanding
      the mechanisms of the repair process is a key for the design of oligonucleotides
      capable to induce gene repair more efficiently and precisely. The future of this
      technology will depend, ultimately, on the development of safe delivery systems
      capable to target a large number of muscles. Furthermore, before using
      oligonucleotides into a clinical setting, we will need to evaluate issues of
      toxicity, which will have to be balanced with the severity of the disease and the
      prognosis of the patient. Finally, the rapid progress that has been made to scale
      up the production of synthetic oligonucleotides will enable the synthesis from
      micrograms to milligrams quantities allowing this field to move from the bench to
      the bedside. This review will describe the basic mechanisms of oligonucleotide
      mediated gene editing and will explain the potential, hurdles and substantial
      results obtained using this technology in the treatment of muscular dystrophies.

PMID- 16629054
TI  - Non-viral approaches for gene transfer.
AB  - Gene therapy has great potential to treat or prevent a variety of both genetic
      and acquired conditions that include neuromuscular disorders, cardiovascular
      disease, cancer, and infectious diseases. For recessive genetic disorders such as
      Duchenne muscular dystrophy, delivery of the normal dystrophin gene to muscle
      should prevent the myofibers from dying. Despite the great promise and sound
      principles of gene therapy, its application to humans have been hampered by the
      inability to safely and effectively deliver genes to the target tissues. Among
      the several gene transfer methods under development, the use of non-viral
      delivery methods and specifically naked DNA is particularly attractive in that
      many of the concerns over the use of viral-mediated methods, such as
      immunogenicity of viral packaging proteins and cost of viral vector production
      can be avoided. Recently we used limb veins for efficient, repeatable, and safe
      delivery of nucleic acids to skeletal myofibers throughout the limb muscles of
      mammals in vivo. Promising results have been obtained in both rodents and larger
      animals including non-human primates. Studies in the mdx mouse model indicate
      that the approach should be of use for patients with Duchenne muscular dystrophy.
      Based upon these encouraging results, a human clinical trial to deliver the human
      dystrophin gene to patients with DMD is being planned. The initial objective is
      to preserve hand and forearm function to increase the quality of life.

PMID- 16629055
TI  - Utrophin upregulation in Duchenne muscular dystrophy.
AB  - Duchenne Muscular Dystrophy (DMD) is a devastating, progressive muscle wasting
      disease for which there is currently no effective treatment. DMD is caused by
      mutations in the dystrophin gene many of which result in the absence of the large
      cytoskeletal protein dystrophin at the sarcolemma. Over-expression of utrophin,
      the autosomal paralogue of dystrophin, as a transgene in the mdx mouse (the mouse
      model of DMD) has demonstrated that utrophin can prevent the muscle pathology.
      Thus, up-regulation of utrophin in DMD muscle is a potential therapy for DMD. In
      this review we discuss recent advances in our understanding of the regulatory
      pathways controlling utrophin expression and the various approaches that have
      been applied to increasing the level of utrophin in the mdx mouse. These results
      are very encouraging and suggest that pharmacological up-regulation of utrophin
      may well be a feasible approach to therapy for DMD.

PMID- 16629056
TI  - The modulation of skeletal muscle glycosylation as a potential therapeutic
      intervention in muscular dystrophies.
AB  - Post-translational modification of proteins following glycosylation is a powerful
      tool to increase diversity of proteins and ligand interaction. alpha
      Dystroglycan, a key muscle fibre receptor for various extracellular matrix
      ligands, is very heavily glycosylated. In addition heterogeneity of its
      glycosylation pattern has been described not only in different tissues and
      organs, but also in different regions of skeletal muscle, such as the sarcolemma
      and the neuromuscular junction. This review is focused on the potential of
      hyperglycosylation strategies as a means for therapeutic intervention in several
      forms of muscular dystrophy. Regarding Duchenne muscular dystrophy (DMD)
      overexpression of the synaptic CT GalNAc transferase in the sarcolemma of mdx
      animals was shown to induce the appearance of the CT antigen on the dystroglycan
      expressed at the sarcolemma. This was followed by the recruitment of utrophin at
      the sarcolemma and improved muscle pathology in mdx mice. A related strategy has
      also been used in preclinical models of "dystroglycanopathies". These conditions
      range in severity from severe and congenital onset to milder forms of limb girdle
      muscular dystrophy affecting the adult. The mechanism of disease in
      dystroglycanopathies is presumed to be the uncoupling of the cellular receptor
      alpha-dystroglycan from its extracellular matrix ligands of which laminin is the
      most important one. Recent work has demonstrated that the overexpression of 2
      related glycosyltransferases, LARGE and LARGE L, results in the
      hyperglycosylation of alpha-dystroglycan. This hyperglycosylation can also be
      induced in cells from patients with a dystroglycanopathy, restoring normal
      dystroglycan ligand binding. LARGE and/or LARGE-L up regulation could therefore
      represent a therapeutic option for patients affected by dystroglycanopathies,
      regardless of their primary defect.

PMID- 16629057
TI  - Antisense oligonucleotides, exon skipping and the dystrophin gene transcript.
AB  - Antisense oligonucleotide induced exon skipping has recently emerged as a
      potential therapy to by-pass the consequences of many, but not all dystrophin
      mutations that lead to Duchenne muscular dystrophy. Targeted removal of one or
      more exons, to restore a disrupted reading frame, or omit a nonsense mutation,
      could lessen the consequences of an estimated 80% of dystrophin gene mutations.
      Promising in vitro and in vivo experiments in animal models of
      dystrophinopathies, as well as demonstration of induced exon skipping in cultured
      human myogenic cells have prompted considerable enthusiasm. Furthermore, advances
      in antisense oligonucleotide chemistries have resulted in the development of more
      stable and less toxic compounds, some of which are currently in Phase III
      clinical trials for selected antiviral applications. This review will summarize
      developments in induced exon skipping that have paved the way to clinical trials
      and some of the challenges and possible limitations.

PMID- 16629058
TI  - Molecular mechanisms involving IGF-1 and myostatin to induce muscle hypertrophy
      as a therapeutic strategy for Duchenne muscular dystrophy.
AB  - Over the past decade, signalling cascades have been characterised that control
      key features of muscle growth, including the proliferation, differentiation of
      muscle precursors, the control cell size (hypertrophy) and cell death. In this
      review we highlight how two differing signalling molecules, Insulin-like Growth
      Factor-1 (IGF-1) and myostatin, regulate key steps during muscle development. We
      discuss how IGF-1 and myostatin signalling cascades can be manipulated to
      stimulate muscle growth. We summarise experimental data from mdx mouse, the
      animal model for Duchenne muscular dystrophy, that suggest a therapeutic value of
      these strategies for patients suffering from muscular dystrophy without
      redressing the primary cause of the lesion.

PMID- 16629059
TI  - Corneal topography vs ocular wavefront sensing in the retreatment of highly
      aberrated post surgical eyes.

PMID- 16629060
TI  - Late bilateral keratectasia after LASIK in a low myopic patient.

PMID- 16629061
TI  - Repeat LASIK after penetrating keratoplasty for repair of a corneal perforation
      from previous LASIK.

PMID- 16629062
TI  - Endophthalmitis after Artisan phakic intraocular lens implantation for correction
      of high myopia.

PMID- 16629063
TI  - Topography-guided treatment of irregular astigmatism with the wavelight excimer
      laser.
AB  - PURPOSE: To evaluate the feasibility, safety, and predictability of correcting
      high irregular astigmatism in symptomatic eyes with the use of topography-guided
      photoablation. METHODS: In a prospective, non-comparative case series, 16
      consecutive symptomatic eyes of 11 patients with small hyperopic and myopic
      excimer laser optical zones, decentered and irregular ablation after corneal
      graft, and corneal scars were operated. Uncorrected visual acuity (UCVA), best
      spectacle-corrected visual acuity (BSCVA), manifest and cycloplegic refraction,
      and corneal topography, with asphericity and regularity, were analyzed. LASIK (n
      = 10) and photorefractive keratectomy (n = 6) were performed using the ALLEGRETTO
      WAVE excimer laser and T-CAT software (Topography-guided Customized Ablation
      Treatment; WaveLight Laser Technologie AG, Erlangen, Germany). RESULTS: In the
      LASIK group, UCVA improved from 0.81 +/- 0.68 IogMAR (20/130) (range: 0.2 to 2.0)
      to 0.29 +/- 0.21 logMAR (20/39) (range: 0.1 to 0.7) at 6 months. In the PRK
      group, mean UCVA improved from 0.89 +/- 0.87 IogMAR (20/157) (range: 0.1 to 2.0)
      to 0.42 +/- 0.35 logMAR (20/53) (range: 0.1 to 1.0) at 6 months. Best spectacle
      corrected visual acuity did not change significantly in either group. One PRK
      patient lost one line of BSCVA. Refractive cylinder for the LASIK group improved
      from -2.53 +/- 1.71 diopters (D) (range: -0.75 to -5.75 D) to -1.28 +/- 0.99 D
      (range: 0 to -2.50 D) at 6 months. Refractive cylinder in the PRK group improved
      from -2.21 +/- 2.11 D (range: -0.25 to -5.50 D) to -1.10 +/- 0.42 D (range: -0.50
      to -1.50 D). Index of surface irregularity showed a decrease from 60 +/- 12
      (range: 46 to 89) to 50 +/- 9 (range: 32 to 63) at 6 months in the LASIK group
      whereas no significant change was noted in the PRK group. Subjective symptoms,
      such as glare, halos, ghost images, starbursts, and monocular diplopia, were not
      present postoperatively. CONCLUSIONS: Topography-guided LASIK and PRK resulted in
      a significant reduction of refractive cylinder and increase of UCVA, without a
      significant loss of BSCVA.

PMID- 16629064
TI  - Wavefront-guided enhancements using the wavelight excimer laser in symptomatic
      eyes previously treated with LASIK.
AB  - PURPOSE: To describe our clinical experience in wavefront-guided LASIK
      enhancements using the WaveLight ALLEGRETTO system (WaveLight Technologie AG,
      Erlangen, Germany) for symptomatic eyes previously treated with standard LASIK.
      METHODS: Twenty-six eyes of 20 patients with residual myopia, hyperopia, or mixed
      astigmatism and/or night vision symptoms after primary standard LASIK were
      considered for wavefront-guided customized retreatment using the WaveLight
      ALLEGRETTO WAVE 200 Hz excimer laser system (model 106). Preoperative best
      spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity, topography
      with the ALLEGRETTO Topolyzer, wavefront analysis using the ALLEGRETTO WAVE
      Tscherning Analyzer, and contrast sensitivity were compared to postoperative
      (enhancement) measurements. RESULTS: Twenty-two of the original 26 eyes underwent
      wavefront-guided enhancement, 4 were excluded because they did not meet wavefront
      guided treatment inclusion guidelines of this study. Mean follow-up was 8 months
      (range: 6 to 13 months, standard deviation [SD] 2). All patients were within +/-
      0.50 diopters (manifest refraction) of intended postoperative refraction. The
      mean preoperative BSCVA improved from 20/25 (SD +/- 0.12) to 20/18 (SD +/- 0.1)
      postoperatively. All patients gained at least one line of BSCVA, and a maximum of
      three lines. There was no loss of BSCVA in any patient. The total amount of high
      order aberrations (RMSH) decreased from an average of 1.04 (SD +/- 0.22) to 0.46
      (SD +/- 0.14) microm. Patients also had a mean improvement in low contrast
      sensitivity of 59%. CONCLUSIONS: Based on this small series, customized wavefront
      guided enhancements using the WaveLight ALLEGRETTO system in patients who
      underwent previous LASIK appear to be safe and effective in correcting residual
      refractive error, reducing high order aberrations, and improving visual symptoms
      when reliable and reproducible measurements are achieved.

PMID- 16629065
TI  - Outcome of LASIK for myopia in women on hormone replacement therapy.
AB  - PURPOSE: To investigate the effect of hormone treatment on refractive and visual
      outcome after LASIK in women. METHODS: A retrospective review of the hospital
      notes of all women on hormone replacement therapy (HRT) and oral contraceptives
      at the time of LASIK was performed. Their refractive and visual outcomes were
      compared with those of women not on hormone treatment. RESULTS: At 6 months after
      LASIK, 20 (45%) HRT eyes and 61 (75%) control eyes had a visual acuity of > or =
      20/20. Thirty-six (82%) eyes from the HRT group and 74 (91%) eyes from the
      control group could see > or = 20/40. A statistically significant difference was
      noted in both refractive and visual outcome in women taking HRT at the time of
      surgery in comparison to controls. Women on the oral contraceptive pill did not
      differ in outcome from controls. CONCLUSIONS: Women on HRT are at an increased
      risk of refractive regression after LASIK.

PMID- 16629066
TI  - Bilateral comparison of corneal flap dimensions with the Moria M2 reusable head
      and single use head microkeratomes.
AB  - PURPOSE: To compare the Moria (Antony, France) M2 automated microkeratome with
      the head 130 to a new disposable single use head to evaluate complications,
      accuracy, and safety of the procedure. METHODS: Ninety-eight eyes of 49
      consecutive patients were operated with the Moria M2 microkeratome. One eye was
      operated with the metallic head 130 and the other with a plastic single use head,
      both designed to create a 160-microm flap. Intraoperative flap dimensions were
      correlated to preoperative parameters and evaluated 1 month postoperatively.
      RESULTS: With the head 130, mean thickness was 153.3 microm (standard deviation
      [SD] 13.3, range: 102 to 179 microm). When using a single use head, mean
      thickness was 148.0 microm (SD 9.8, range: 120 to 170 microm). Occasional iron
      particles were observed in one eye with both head types. No true epithelial
      ingrowth was detected in any of the eyes, but epithelial dots at the wound edge
      occurred in one eye, when using the head 130, but not in the eyes operated with a
      single use head. CONCLUSIONS: On average, both head types created thinner flaps
      than attempted. Single use heads produced thinner flaps than the head 130.
      Accuracy in flap thickness in terms of standard deviation was significantly
      better in single use heads than in the head 130. Single use heads also had fewer
      microkeratome-related complications. In clinical practice, the single use head
      was easier to use because no assembly was required. Plastic single use heads also
      worked more smoothly than the metallic head 130.

PMID- 16629067
TI  - Dry eye after LASIK enhancement by flap lifting.
AB  - PURPOSE: To determine whether dry eye after LASIK recurs after LASIK enhancement.
      METHODS: A total of 63 eyes of 42 patients who underwent LASIK enhancement were
      included in this study. Subjective dry eye symptoms, tear break-up time (BUT),
      Schirmer test with anesthesia, fluorescein staining of the cornea, and corneal
      sensitivity were evaluated before and at 1, 3, and 6 months after enhancement.
      RESULTS: The subjective dry eye symptoms remained unchanged before and after
      LASIK enhancement. Similarly, Schirmer values and tear BUT did not exhibit
      statistically significant differences between the pre- and post-enhancement
      values. Compared with the pre-enhancement values, the fluorescein score was
      higher at 1 month after surgery and further improved at 3 months. In comparison
      with the pre-enhancement values, the corneal sensitivity was decreased at 1, 3,
      and 6 months after surgery. CONCLUSIONS: Patients did not complain of dry eye
      symptoms and tear functions were not compromised after LASIK enhancement. These
      results suggest that factors other than the neurotrophic effect may contribute to
      dry eye after LASIK.

PMID- 16629068
TI  - Pachymetry assessment with Orbscan II in postoperative patients with myopic
      LASIK.
AB  - PURPOSE: To compare central corneal thickness after LASIK for myopia, using
      ultrasonic pachymetry and Orbscan II measurements, and to evaluate changes in
      these measurements over time. METHODS: Central corneal thickness measurements
      obtained by ultrasonic pachymetry and Orbscan II (Bausch and Lomb, Rochester, NY)
      in patients who underwent myopic LASIK between July 2002 and May 2003 were
      analyzed. The two measurements were assessed preoperatively and postoperatively
      at 1 day and 1, 3, 6, and 12 months. RESULTS: In 237 eyes, using the correction
      factor 0.93, no significant difference was noted in the preoperative central
      corneal thickness measured by ultrasonic pachymetry (561.89 +/- 28.66 microm) and
      Orbscan pachymetry (562.28 +/- 28.18 microm) (P =.713). Postoperatively, the
      difference was statistically significant at day 1 and 1, 3, and 6 months (P <
      .001), but was not significant at 12 months (P = .130). CONCLUSIONS: Orbscan II
      measurements of central corneal thickness after myopic LASIK are less than those
      measured by ultrasonic pachymetry; however, this difference decreases with time
      and may not be significant after 1 year.

PMID- 16629069
TI  - Evaluation of pupil dynamics after implantation of artisan phakic intraocular
      lenses.
AB  - PURPOSE: To compare pre- and postoperative horizontal and vertical pupil
      diameters after horizontal Artisan phakic intraocular lens (PIOL) (Ophtec BV,
      Groningen, The Netherlands) implantation for correction of myopia. METHODS: The
      pre- and postoperative scotopic pupil diameters measured by the Colvard
      pupillometer (Oasis Medical, Glendora, Calif) were compared in 71 eyes after
      Artisan PIOL implantation (Artisan Colvard group). Analysis of pupil shape
      (vertical vs horizontal diameter, V/H ratio) after horizontal Artisan PIOL
      implantation was performed with the Procyon pupillometer (Procyon Instruments
      Ltd, London, United Kingdom) in 121 eyes (Artisan Procyon group) under scotopic,
      mesopic-low, and mesopic-high conditions and compared to an age- and refraction
      matched control group of 121 eyes of refractive surgery candidates (Procyon
      control group). RESULTS: After horizontal Artisan PIOL implantation, the mean
      horizontal pupil diameter decreased from 6.231 +/- 0.70 mm preoperatively to 5.34
      +/- 0.68 mm postoperatively in the Artisan Colvard group (P < .01). The mean
      horizontal scotopic diameter was 5.60 +/- 0.66 mm, the mesopic-low diameter was
      4.94 +/- 0.71 mm, and the mesopic-high diameter was 3.98 +/- 0.54 mm for the
      Artisan Procyon group. The mean horizontal scotopic diameter was 6.29 +/- 0.91
      mm, the mesopic-low diameter was 5.40 +/- 0.96 mm, and the mesopic-high diameter
      was 4.16 +/- 0.80 mm in the Procyon control group. A significant increase was
      noted in V/H ratio under scotopic, mesopic-low, and mesopic-high conditions from
      1.02, 1.02, and 1.01, respectively, in the Procyon control group to 1.17, 1.12,
      and 1.06, respectively, in the Artisan Procyon group (P < .01). CONCLUSIONS:
      Horizontal pupil size was significantly decreased after horizontal Artisan PIOL
      implantation and might be attributed to a mechanical restriction of the iris in
      the horizontal meridian.

PMID- 16629070
TI  - Optic disc and retinal nerve fiber layer analysis with scanning laser tomography
      after LASIK.
AB  - PURPOSE: To examine whether LASIK induces changes in the optic disc and retinal
      nerve fiber layer using scanning laser tomography. METHODS: Prospective,
      consecutive study of 53 myopic eyes in 38 patients (mean age: 35.7 +/- 10.4
      years; range: 22 to 58 years). Preoperative average refractive error was -6.0 +/-
      2.4 diopters (D) (spherical equivalent) (range: -2.0 to -10.0 D). Optic disc
      morphology and retinal nerve fiber layer thickness were evaluated with scanning
      laser tomography preoperatively and at 7 and 13 months postoperatively. RESULTS:
      No statistically significant differences were noted between the pre- and
      postoperative optic disc and retinal nerve fiber layer measurements. CONCLUSIONS:
      Our results suggest that transient extreme elevation of intraocular pressure
      during LASIK does not affect the optic disc morphology or retinal nerve fiber
      layer thickness in normal myopic eyes for at least 1 year after surgery.

PMID- 16629071
TI  - Very high-frequency ultrasound analysis of non-contact holmium laser thermal
      keratoplasty treatment spots.
AB  - PURPOSE: To objectively measure the corneal treatment spots in vivo using very
      high-frequency ultrasound (VHFU) after non-contact laser thermal keratoplasty
      (LTK) to better understand the variability and regression of refractive outcomes.
      METHODS: In an institutional setting, VHFU was performed on 128 spots (8 eyes of
      4 patients) using an immersion scanning technique 1 to 2 years after LTK with a
      single element focused transducer (50 MHz arc scanning ultrasound). Biometric
      techniques were used to evaluate the treatment spot depth, corresponding corneal
      thickness, and spot profile between patients, eyes (left/right), and by location
      on the cornea. The identical technique was used in a rabbit immediately after LTK
      to compare ultrasound versus histologic findings. RESULTS: The mean treatment
      spot penetration depth ranged between 0.373 and 0.533 mm, representing 64% to 78%
      of the corneal thickness compared to previous reports of 80% to 90%. Treatment
      spot depth, the corresponding corneal thickness, and percentage of overall cornea
      penetrated differed significantly across patients. Treatment spot depth was not
      significantly related to the level of applied laser energy (230 to 258 mJ) (0.082
      Pearson sign). Spot profiles were not uniformly cone-shaped; W- and wedge-shaped
      were also identified. Ultrasound findings in the rabbit were similar to histology
      results and confirmed evidence of epithelial remodeling. CONCLUSIONS: Very high
      frequency ultrasound of 128 treatment spots after non-contact LTK demonstrates
      epithelial remodeling and inconsistencies in penetration depth and profile.

PMID- 16629072
TI  - Analysis of intraocular lens power calculation for eyes with previous myopic
      LASIK.
AB  - PURPOSE: To evaluate the effectiveness of a manual keratometry (K) adjusted value
      for intraocular lens (IOL) power calculation in patients who underwent cataract
      surgery following previous myopic LASIK. METHODS: Sixteen eyes of 14 consecutive
      patients who underwent cataract surgery after previous LASIK were evaluated
      retrospectively. All IOL powers were calculated using an adjusted K value (K
      minus 1.0 diopter [D]) with the Binkhorst II formula aiming for -0.75 to -1.00 D
      final refraction. Additionally, the IOL power for each eye was retrospectively
      calculated using K, refractive-derived K, and adjusted K with the Binkhorst II,
      Holladay I, and SRK/T formulas. The final refraction was used as a criterion of
      accuracy of each approach. RESULTS: Uncorrected visual acuity > or = 20/40 was
      achieved in 14 (87.5%) of 16 eyes. The mean postoperative spherical equivalent
      refraction was -0.41 +/- 0.57 D (range: +0.50 to -2.00 D). Twelve (75%) of 16
      eyes were within +/- 0.50 D of emmetropia and 15 (94%) of 16 eyes were within +/-
      1.00 D. No eye was > +1.00 D. CONCLUSIONS: Using an adjusted K with the Binkhorst
      II formula, aiming for -0.75 to -1.00 D, and with the Holladay I formula, aiming
      for -0.50 to -1.00 D, measuring K with a regular manual keratometer permits
      determination of an IOL power after myopic LASIK without the need of preoperative
      LASIK refractive data.

PMID- 16629073
TI  - Retreatment of LASIK.
AB  - PURPOSE: To review the indications, techniques, and results of retreatment LASIK.
      METHODS: Review of the literature and the authors' experience. RESULTS: Patient
      selection is the key to successful LASIK enhancement. The enhancement procedure
      should generally be undertaken 3 months after the initial LASIK procedure.
      Relifting of the flap may be done easily within 1 year of previous LASIK surgery.
      A new LASIK flap is required in cases with previously complicated LASIK. LASIK
      retreatment by lifting the flap is an effective and safe procedure. Overall
      improvement is seen in uncorrected visual acuity (> or = 20/20 and > or = 20/40)
      and postoperative spherical equivalent refraction within +/- 0.5 D and +/- 1.0 D.
      CONCLUSIONS: LASIK retreatment is an effective modality to treat regressions and
      residual refractive errors.

PMID- 16629074
TI  - Traumatic late flap dehiscence and Enterobacter keratitis following LASIK.
AB  - PURPOSE: To report a case of traumatic flap dehiscence and Enterobacter keratitis
      34 months after LASIK. METHODS: A 36-year-old man sustained a flap dehiscence
      following traumatic right eye gouging by a seagull claw. He presented the
      following day with uncorrected visual acuity (UCVA) in the affected eye of 3/200
      and organic foreign body deposits underneath the flap. Systemic and topical
      antibiotics were administered and urgent surgical debridement and replacement of
      the LASIK flap was performed. An Enterobacter species was cultured from an
      intraoperative swab. RESULTS: After a prolonged postoperative course, including
      administration of topical ofloxacin, tobramycin, chloramphenicol, and
      dexamethasone, UCVA returned to 20/20. CONCLUSIONS: Good visual outcome after
      early debridement and appropriate antibiotics was achieved. Patients should be
      injury advised to seek prompt ophthalmic consultation after LASIK.

PMID- 16629075
TI  - Prophylactic perioperative antiviral therapy for LASIK in patients with inactive
      herpetic keratitis.
AB  - PURPOSE: To report the outcome of LASIK in patients with inactive herpetic
      keratitis in which perioperative antiviral prophylaxis was used to prevent the
      recurrence of ocular herpes. METHODS: We report an uncontrolled series of five
      patients with inactive herpetic keratitis for at least 1 year before surgery in
      whom LASIK was successfully performed. All patients showed normal topography,
      pachymetry, and corneal sensitivity with no central corneal scarring.
      Perioperative prophylaxis was used in each case with oral valacyclovir and
      topical acyclovir ointment. RESULTS: None of the eyes developed reactivation of
      herpetic keratitis during follow-up. CONCLUSIONS: This study suggests that
      perioperative antiviral prophylaxis may protect the cornea from herpes simplex
      virus reactivation after LASIK.

PMID- 16629076
TI  - NeuroVision treatment for low myopia following LASIK regression.
AB  - PURPOSE: To evaluate a novel non-surgical method for improving vision in a
      refractive surgery patient. METHODS: A 45-year-old man who had undergone LASIK 5
      years previously presented with blurred distance vision. Unaided vision in the
      right eye was 20/329-2) and 20/20 in the left eye. He enrolled for NeuroVision
      treatment (NeuroVision Pte Ltd, Singapore), a computer-based interface in which a
      repetitive set of visual excerises is performed for 10 to 12 weeks. RESULTS:
      After 35 sessions, unaided visual acuity in the right eye was 20/16(-3) and
      20/20(-1) in the left eye, representing 2.8 lines of improvement in the right eye
      and 1.6 lines in the left eye. CONCLUSIONS: NeuroVision, a noninvasive treatment
      based on the concept of perceptual learning, is a benefit in cases in which
      surgical enhancement is not recommended.

PMID- 16629077
TI  - Photorefractive keratectomy in megalophthalmos anterior.
AB  - PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) for the
      correction of myopia and myopic astigmatism in megalophthalmos anterior. METHODS:
      Four eyes of two brothers with megalophthalmos anterior were treated with PRK. In
      patient 1, best spectacle-corrected visual acuity (BSCVA) was 20/20 in both eyes
      with a refraction of -4.50 -4.50 x 180 degrees in the right eye and -3.75 -3.00 x
      175 degrees in the left eye. In patient 2, BSCVA was 20/25 in both eyes with a
      refraction of -4.25 x 166 degrees in the right eye and +0.50 -4.00 x 175 degrees
      in the left eye. RESULTS: Topographic map, slit-lamp, ultrasound biomicroscopy,
      and postoperative course (no progression), supported with vectorial analysis,
      demonstrated megalophthalmos anterior. During 24-month follow-up, mild haze was
      observed and BSCVA was maintained. CONCLUSIONS: Myopia and astigmatism are often
      observed in this type of nonprogressive corneal dysgenesis. Based on this fact
      and our results, we recommend PRK in cases of megalophthalmos anterior.

PMID- 16629078
TI  - [Hypereosinophilic asthma].
AB  - Hypereosinophilic asthma (defined by blood eosinophils > 1 G/L, especially > 1.5
      G/L) may be solitary (and often difficult to treat), or a manifestation of a
      hypereosinophilic disorder of determined cause (parasitic, iatrogenic, allergic
      bronchopulmonary aspergillosis) or idiopathic (idiopathic chronic eosinophilic
      pneumonia, Churg-Strauss syndrome, idiopathic hypereosinophilic syndrome). In
      addition to etiologic treatment when available long term corticosteroids are
      necessary in a majority of patients.

PMID- 16629079
TI  - [Diagnosis and treatment of gastrointestinal stromal tumours].
AB  - Gastrointestinal stromal tumours (GISTs) are most common in the stomach (60-70%),
      followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%).
      They are characterized by expression of the transmembrane receptor tyrosine
      kinase KIT, which is defined by the CD117 antigen and is the product of the kit
      proto-oncogene. Metastatic risk is based on tumour size and mitotic count. The
      treatment options have evolved rapidly with the discovery of imatinib (Gleevec)
      that selectively inhibits KIT. Complete resection without tumour rupture remains
      the mainstay of treatment in patients with localized, resectable disease.
      Imatinib has been shown to be the first successful systemic therapy for patients
      with metastatic or unresectable disease and is also currently being tested as an
      adjuvant therapy after the resection of high risk primary GIST. New blockers of
      the tyrosine-kinase activity are currently in development in cases of resistance.

PMID- 16629080
TI  - [Splenic artery aneurysm].

PMID- 16629081
TI  - [Behavioral problems in children: figuring out what is normal and what is
      worrisome].

PMID- 16629082
TI  - [What is child attention deficit hyperactivity disorder?].
AB  - Prevalence of attention deficit hyperactivity disorder (ADHD) is around 5%. The
      main clinical criteria of ADHD are hyperactivity, impulsivity and attention
      deficit. Several clinical patterns are described. ADHD symptomatology change with
      age but always start before 7 years old. Comorbidity is frequent and it is
      important to distinguish ADHD and another differential diagnostic. Disorder
      mechanism is complex and associate several factors mainly neurobiologicals and
      genetics. For diagnostic, we use a clinical approach. Some questionnaires,
      cognitive and attentional tests can help for. It is important to take into
      account parent, child, caregiver and professor observations. Developmental
      evaluation is necessary for diagnostic and therapeutic strategy.

PMID- 16629083
TI  - [Treatment of attention deficit/hyperactivity disorder].
AB  - Attention deficit/hyperactivity disorder (ADHD) is a chronic and invalidating
      condition, whose negative consequences on psychosocial functioning calls for
      efficacious treatment plans. Several treatments have been proven to be effective:
      some parent and children treatment programs, psychostimulants, atomoxetine. Most
      of these therapeutic options are not easily available to patients and families
      (psychoeducational programs are rarely used in France). Primary care
      professionals can help families to access valid information, discuss treatment
      plans and monitor treatment.

PMID- 16629084
TI  - [Conduct disorder in childhood].
AB  - Conduct disorder is a repetitive and persistent pattern of behaviour in which the
      basic rights of others or societal rules are violated. It is at the junction of
      psychiatry, social field and law. The early diagnosis of this disorder and the
      identification of risk factors must go to preventive programs and psycho
      educational treatments, to prevent juvenile delinquency.

PMID- 16629085
TI  - [Oppositional behavior in children and adolescents].
AB  - Opposition is a natural and beneficial process for children to shape their
      personality, it is a necessary step in their own and parents' life. It challenges
      the five rules governing children's life: parents' educational principles, school
      constraints, social rules, rules with "peers" and children's own rules. However,
      opposition can become pathological: symptoms of oppositional behaviors include
      defying requests, psychosomatic disorders in infants, offending behavior and
      oppositional defiant disorder. It is essential to identify them, encourage active
      family participation and look for a coexisting psychological condition.
      Oppositional disorders should be managed rapidly to prevent them from becoming
      chronic or evolving towards oppositional defiant or conduct disorders.

PMID- 16629086
TI  - [Behavior disorders of the gifted child].

PMID- 16629087
TI  - [Child behavior disorders in MEDLINE].

PMID- 16629088
TI  - [Advice to parents and teachers of hyperactive children].

PMID- 16629089
TI  - [Clinical experience and quality of care].

PMID- 16629090
TI  - [Diagnosis of diplopia].

PMID- 16629091
TI  - [Non-traumatic medullary compression and cauda equina].

PMID- 16629092
TI  - [Suicidal risk in children, adolescents and adults].

PMID- 16629093
TI  - [Acute and chronic dyspnea].

PMID- 16629094
TI  - [Chronic lymphocytic leukemia].

PMID- 16629095
TI  - [Psychomotor development and infants and children].

PMID- 16629096
TI  - [Some aspects of medicine in ancient Mesopotamia].

PMID- 16629097
TI  - RNs err in using 'unwashed' sperm for insemination.

PMID- 16629098
TI  - 'Telephone triage' is 'risky business' for nurses.

PMID- 16629099
TI  - PA: failure to disclose history of prior injuries: denial of Workers'
      Compensation benefits upheld.

PMID- 16629100
TI  - RNs were negligent but not 'proximate cause' of patient's death.

PMID- 16629101
TI  - Balancing cure with care.

PMID- 16629102
TI  - Playing the cost-cutting game.

PMID- 16629103
TI  - Russian revelation.
AB  - Jill McGowan was convinced that a programme of breathing retraining--the Buteyko
      Method - could reduce the medication needs of people with asthma. So she gave up
      her nursing job and sold her house and car to finance research. Training requires
      five 90-minute sessions. The 30-minute exercise programme has to be repeated six
      times a day initially. Introduction of the method to the NHS could have a major
      impact on asthma management with potentially huge savings on cost.

PMID- 16629104
TI  - Special effects.
AB  - The nursing team on the day case ward at Alder Hey Hospital has introduced
      changes to the environment to help children with special needs, who often attend
      the ward repeatedly. Small changes, such as keeping colours on the ward neutral,
      can help children relax. Nurses contact parents a week before admission to find
      out about their child's likes and dislikes. Parents are encouraged to bring a
      child's favourite items with them. Operating sessions are scheduled to meet these
      children's needs.

PMID- 16629105
TI  - Flood of support.
AB  - A year on from the torrential floods that struck Cumbria, many people are still
      unable to return to their homes. A team of therapists is helping people to cope
      with the stress and frustration. The January 2005 floods came four years after
      foot and mouth disease hit Cumbria. The region depends on agriculture, hill
      walking and tourism for revenue. Therapists offer residents a choice of eight,
      different complementary therapies. Users of the service say the therapies reduce
      stress and help them relax.

PMID- 16629106
TI  - Get back to work and wellbeing.

PMID- 16629107
TI  - Mum's gone travelling.

PMID- 16629108
TI  - Time to grow up.

PMID- 16629109
TI  - The importance of exercise training in patients with chronic heart failure.
AB  - This article discusses the cardiac care and rehabilitation needs of patients with
      chronic heart failure (CHF). Research suggests that patients with CHF who are in
      a stable condition can undertake supervised exercise programmes. Patients are
      rarely prescribed exercise; however exercise in patients with CHF reduces
      mortality and hospital admission rates. Improvements have also been demonstrated
      in symptoms and quality of life. It is recommended that exercise programmes are
      provided and that all-cause mortality is used as an indication of treatment
      efficacy, because it is the most unbiased outcome measure.

PMID- 16629110
TI  - Redesign of medicine supply systems in a rehabilitation hospital.
AB  - This article describes the process of introducing the use of patients' own drugs,
      one-stop dispensing and self-medication in a rehabilitation hospital. It also
      describes nurses' and patients' opinions of the new medication administration
      system before and after its introduction.

PMID- 16629111
TI  - Mentoring learners in practice: No. 20. Helping learners to evaluate care.

PMID- 16629112
TI  - Management of patients with intermittent claudication.
AB  - Intermittent claudication is a common manifestation of peripheral arterial
      disease, its symptoms have a gradual onset and the patient may not notice them
      initially, instead accepting them as part of the ageing process. The main concern
      with intermittent claudication is the increased risk of cardiovascular or
      cerebrovascular events. This article highlights the relationship between these
      diseases and suggests ways to reduce risk and promote best practice.

PMID- 16629113
TI  - Wound assessment.

PMID- 16629114
TI  - Talking points.

PMID- 16629115
TI  - Critical experience counts.

PMID- 16629116
TI  - Talk the talk.

PMID- 16629117
TI  - Comparison between properties of 2'-O,4'-C-ethylene-bridged nucleic acid (ENA)
      phosphorothioate oligonucleotides and N3'-P5' thiophosphoramidate
      oligonucleotides.
AB  - Synthesis and properties of an oligonucleotide uniformly modified with 2'-O,4-C
      ethylene-bridged nucleic acid (ENA) units were compared with those of GRN163,
      which is modified with N3'-P5' thiophosphoramidates, with the sequence targeting
      human telomerase RNA subunit. Although an ENA phosphorothioate oligonucleotide,
      ENA-13, could be synthesized using ENA phosphoramidites on a 100-mg scale,
      synthesis of GRN163 was very hard even on a 1-micomol scale. In view of both
      stability of the duplex formation with complementary RNA and the efficiency of
      cellular uptake by endocytosis, ENA-13 was superior to GRN163. These findings
      suggest that ENA-13 has useful properties for antisense therapeutic application.

PMID- 16629118
TI  - Synthesis and RT inhibitory activity evaluation of new pyrimidine-based seco
      nucleosides.
AB  - Eleven new 3',4'-seco acyclic nucleosides (4-14) were prepared by nucleophilic
      substitution of protected pyrimidine bases on ethyl 3,3-diethoxypropanoate (3).
      Structures were characterized spectroscopically and a brief analysis of their
      conformation in solution was performed by the vicinal coupling constants
      (3)JH2'aH3' and (3)JH2'bH3'. In solid state, compound 6 forms a homodimer linked
      by hydrogen bonding. In preliminary tests all compounds show low toxicity and
      gentle activity against HIV-1 RT in vitro.

PMID- 16629119
TI  - Time and concentration dependence of Fenton-induced oxidation of dG.
AB  - The influence of incubation time and Fenton reagent concentrations was
      investigated on the oxidation of 2'-deoxyguanosine. The compounds identified and
      quantified, through use of an LC-MS/MS system, were 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) and 8,5'-cyclo-2'-deoxyguanosine (8,5'cyclodG) and the
      secondary oxidation products guanidinohydantoin and dehydro-guanidinohydantoin. 8
      oxodG and 8,5' cyclodG formed very quickly, reaching a maximum rapidly, but with
      8-oxodG a rapid decline occurred thereafter due to its further oxidation into the
      secondary products, which formed more slowly. Due to the better stability, 8,5'
      cyclodG correlated better with the general level of oxidation than 8-oxodG. The
      results emphasize the advantages of measuring other oxidation adducts than 8
      oxodG alone.

PMID- 16629120
TI  - The photochemistry of 5-BrdCpdC, dCp5-BrdCpdA, and dCp5-BrdCdT in aqueous
      solution.
AB  - We isolated an intrastrand crosslink product from the Pyrex-filtered UV light
      irradiation of 5-BrdCpdC in aqueous solution. ESI-MS, MS/MS, and 2-D nuclear
      Overhauser effect spectroscopy (NOESY) results showed that the C5 carbon atoms of
      the two cytosines are covalently bonded. The same cross-link product can also be
      induced from the similar UV irradiation of dCp5-BrdCpdA and dCp5-BrdCpdT.

PMID- 16629121
TI  - F-ara-AMP is a substrate of cytoplasmic 5'-nucleotidase II (cN-II): HPLC and NMR
      studies of enzymatic dephosphorylation.
AB  - Intracellular accumulation of triphosphorylated derivatives is essential for the
      cytotoxic activity of nucleoside analogues. Different mechanisms opposing this
      accumulation have been described. We have investigated the dephosphorylation of
      monophosphorylated fludarabine (F-ara-AMP) by the purified cytoplasmic 5'
      nucleotidase cN-II using HPLC and NMR. These studies clearly showed that cN-II
      was able to convert F-ara-AMP into its non phosphorylated form, F-ara-A, with a
      Km in the millimolar range and Vmax = 35 nmol/min/mg, with both methods.
      Cytoplasmic 5'-nucleotidase cN-II can degrade this clinically useful cytotoxic
      nucleoside analogue and its overexpression is thus likely to be involved in
      resistance to this compound.

PMID- 16629122
TI  - Synthesis of AZT analogues: 7-(3-azido-2-hydroxypropyl)-, 7-(3-amino-2
      hydroxypropyl)-,7-(3-triazolyl-2-hydroxypropyl)theophylline.
AB  - Nucleophilic displacement of the tosyloxy group in 7-(2-hydroxy-3-p
      toluenesulfonyloxypropyl)theophylline (1) with azide anion afforded 7-(3-azido-2
      hydroxypropyl)theophylline (2). Reduction of the 3-azido group in 2 with
      Ph3P/Py/NH4OH afforded the 3-amino derivative 4, alternatively obtained by
      regioselective amination of 7-(2,3-epoxypropyl)theophylline (3). Selective
      acetylation of 4 gave the N-acetyl derivative 5. 1,3-Dipolar cycloaddition of the
      azide group in 2 with N1-propargyl thymine (6) afforded the regioisomeric
      triazole 7.

PMID- 16629123
TI  - An efficient process for synthesis of 2'-O-methyl and 3'-O-methyl guanosine from
      2-aminoadenosine using diazomethane and the catalyst stannous chloride.
AB  - An improved strategy for the selective synthesis of 2'-O-methyl and 3'-O-methyl
      guanosine from 2-aminoadenosine is reported by using the catalyst stannous
      chloride. The regioselectivity of the 2' and 3'-O-alkylation was achieved by
      optimizing the addition, timing, and concentration of the catalysts and
      diazomethane during the methylation reaction. An efficient and selective
      alkylation at 2'-OH of 2-aminoadenosine was achieved by mixing a stoichiometric
      amount of stannous chloride at room temperature in DME The reaction mixture was
      stirred at 50 degrees C for 1 min and immediately followed by addition of
      diazomethane. The resulting 2'-O-methyl 2-aminoadenosine was treated with the
      enzyme adenosine deaminase, which resulted in an efficient conversion to the
      desired 2'-O-methylguanosine (98% yield). The product was isolated by
      crystallization. In contrast, the methylation at 3'-OH of 2-aminoadenosine was
      achieved by mixing a stoichiometric amount of stannous chloride in DMF and
      stirring at 50 degrees C for 15 min, followed by addition of diazomethane. The
      resulting mixture containing 3'-O-methyl-2-aminoadenosine in 90% yield and 2'-O
      methyl-2-aminoadenosine in 10% yield was treated with the enzyme adenosine
      deaminase, which preferentially deaminated only 3'-O-methyl-2-aminoadenosine,
      resulting in the production of 3'-O-methylguanosine in 88% yield. Due to the
      extremely low solubility 3'-O-methylguanosine, the compound precipitated and was
      isolated by centrifugation. This synthetic route obviates the chromatographic
      purification. Selective monomethylation is achieved by using the unprotected
      ribonucleoside. As a result, the method described herein represents a significant
      improvement over the current synthetic approach by providing superior product
      yield and economy, a much more facile purification of 2',3'-O-methylated isomers,
      and eliminating the need for protected ribonucleosides reagents.

PMID- 16629124
TI  - Hydrolytic stability of a phosphate-branched oligonucleotide incorporating a
      ribonucleoside 3'-phosphotriester unit.
AB  - A phosphate-branched oligonucleotide has been prepared by using an appropriately
      protected trinucleoside phosphotriester building block in conventional solid
      phase synthesis. Hydrolysis of the branched oligonucleotide has been followed
      over a wide pH range. Comparison of the present results with those previously
      obtained for simpler analogues indicates that a trinucleoside 3',3',5'
      monophosphate, when embedded in an oligonucleotide structure, is stabilized
      toward hydroxide-ion catalyzed cleavage by more than one order of magnitude,
      lending some support to the feasibility of existence of phosphate-branched RNA X
      in biological systems.

PMID- 16629125
TI  - Microwave-assisted organic synthesis of 3-(D-Gluco-pentitol-1-yl)-1H-1,2,4
      triazole.
AB  - The condensation of D-glucono- and D-galactono-1,5-lactone and thiocarbohydrazide
      to give 3-(D-alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles 4 and 5 is
      accelerated by the use of microwave-assisted organic reaction (MAOS). The
      deamination and dethiolation of compound 4 to give 6 was also accelerated by the
      use of MAOS. Condensation of 4 and 5 with p-nitrobenzaldehyde afforded Schiff
      bases 8 and 9, respectively, within 4 min under microwave irradiation (MWI),
      whereas with ethyl chloroacetate the thioalkylated products 14 and 15 were
      obtained in 8 min. The structures of the synthesized compounds were confirmed by
      1H NMR, 2D NMR, and mass spectra.

PMID- 16629126
TI  - An industrial process for selective synthesis of 7-methyl guanosine 5'
      diphosphate: versatile synthon for synthesis of mRNA cap analogues.
AB  - We report an industrial scale facile synthesis of 7-methyl guanosine 5'
      diphosphate, which plays an important role in synthesis of various mRNA cap
      analogs. An efficient and selective methylation at position 7 of guanosine 5'
      diphosphate was achieved by dissolving guanosine 5'-diphosphate in water and
      drops wise addition of dimethyl sulfate over a period of 1 h at room temperature.
      The reaction was completed within 2 h and resulted in more than a 96% yield. The
      desired product, 7-methyl GDP was purified by using BPG column on AKTA Purifier
      100. Certainly, this method has advantages over the known methylation method, in
      terms of yield, economy, safety, and environmental concerns.

PMID- 16629127
TI  - Synthesis and antiviral evaluation of novel open-chain analogues of neplanocin A.
AB  - Novel acyclic nucleoside analogues were designed and synthesized as open-chain
      analogues of neplanocin A. The coupling of the allylic bromide with purine bases
      using cesium carbonate afforded a series of novel acyclic nucleosides. The
      synthesized compounds Ia-II were evaluated for their antiviral activity against
      various viruses such as HIV HSV-1, HSV-2, and ECMV.

PMID- 16629128
TI  - Reduction of perchlorate in river sediment.
AB  - The transformation of perchlorate was investigated in river sediment during
      laboratory batch and column studies to determine if reduction of perchlorate is a
      viable pathway in natural sediment without previous exposure to perchlorate.
      Perchlorate at an initial concentration of 10 microM was reduced quantitatively
      to chloride in 3 d after a lag phase of 2 d in sediment slurries amended with
      lactate. Raising the initial concentration of perchlorate to 1,000 microM
      increased the lag phase to 20 d before reduction occurred. At perchlorate
      concentrations greater than 1,000 microM, the reduction of perchlorate was not
      observed within 40 d. We speculate that the high concentration of perchlorate
      specifically was problematic to the microbes mediating the reduction of
      perchlorate. High levels of nitrate inhibited the reduction of perchlorate as
      well. In sediment slurries amended with 870 microM sodium nitrate, the reduction
      of perchlorate at an initial concentration of 100 microM did not occur before day
      15 of the experiment, but complete removal of nitrate had occurred by day four.
      Sediment column studies further demonstrated the dependence of perchlorate
      reduction on endogenous nitrate levels.

PMID- 16629129
TI  - The effect of pH and ionic strength on the sorption of sulfachloropyridazine,
      tylosin, and oxytetracycline to soil.
AB  - Antimicrobial agents are the most heavily used pharmaceuticals in intensive
      husbandry. Their usual discharge pathway is application to agricultural land as
      constituents of animal manure, which is used as fertilizer. Many of these
      compounds undergo pH-dependent speciation and, therefore, might occur as charged
      species in the soil environment. Hence, pH and ionic strength of the soil
      suspension can affect the sorption behavior of these compounds to soil.
      Consequently, the soil sorption of three antimicrobial agents-
      sulfachloropyridazine (SCP), tylosin (TYL), and oxytetracycline (OTC)--was
      investigated. Their respective sorption coefficients in two agricultural soils
      ranged from 1.5 to 1,800 L/kg. Sorption coefficients were greater under acidic
      conditions. Addition of an electrolyte to the solution led to decreased sorption
      of TYL and OTC by a factor of 3 to 20, but it did not influence the sorption of
      SCP. This behavior was analyzed by accounting for the pH-dependent speciation of
      TYL and OTC and considering the presence of OTC-calcium complexes. It appears
      that the decreased sorption of TYL and OTC with increasing ionic strength results
      from competition of the electrolyte cations with the positively charged TYL
      species and the positively charged OTC complexes. A model linking sorbate
      speciation with species-specific sorption coefficients can describe the pH
      dependence of the apparent sorption coefficients. This modeling approach is
      proposed for implementation in the assessment of sorption of ionizable compounds.

PMID- 16629130
TI  - A molecular modeling analysis of polycyclic aromatic hydrocarbon biodegradation
      by naphthalene dioxygenase.
AB  - A theoretical analysis was performed to examine the role of naphthalene
      dioxygenase (NDO) enzymes in determining differences in biodegradability and
      biodegradation rates of two- to four-ring polycyclic aromatic hydrocarbons (PAHs)
      via oxygenation and desaturation reactions. Investigation of the thermodynamics
      of PAH biodegradation reactions catalyzed by NDO revealed that enthalpies of
      reaction can explain reaction patterns or regioselectivity of the enzyme in
      limited cases. Molecular modeling analysis of the size and shape constraints of
      PAH-enzyme interactions suggests that PAHs bigger than approximately four rings
      and compounds with alpha substituents or other structural features contributing
      to increased width at the end of the substrate near the active site are expected
      to have binding difficulties. This explains some regioselectivity observations,
      in that thermodynamically favorable sites on some PAH molecules cannot be
      positioned correctly to be oxidized at the active site. The enzyme fit analysis
      also suggests that slower biodegradation rates are expected for compounds with
      larger widths because of the unique positioning that is required for reaction to
      occur. An inverse relationship between a molecular descriptor of compound width
      and previously obtained biodegradation rates suggests that this descriptor may be
      valuable for predicting relative biodegradation rates of PAHs with dioxygenases
      other than NDO.

PMID- 16629131
TI  - Source apportionment modeling of volatile organic compounds in streams.
AB  - It often is of interest to understand the relative importance of the different
      sources contributing to the concentration c(w) of a contaminant in a stream; the
      portions related to sources 1, 2, 3, etc. are denoted c(w,1), c(w2), c(w3), etc.
      Like c(w), the fractions alpha1 = c(w,1)/c(w), alpha2 = c(w,2)/c(w), alpha3 =
      c(w,3)/c(w), etc. depend on location and time. Volatile organic compounds (VOCs)
      can undergo absorption from the atmosphere into stream water or loss from stream
      water to the atmosphere, causing complexities affecting the source apportionment
      (SA) of VOCs in streams. Two SA rules are elaborated. Rule 1: VOC entering a
      stream across the air/water interface exclusively is assigned to the atmospheric
      portion of c(w). Rule 2: VOC loss by volatilization, flow loss to groundwater, in
      stream degradation, etc. is distributed over c(w,1), c(w,2), c(w3), etc. in
      proportion to their corresponding alpha values. How the two SA rules are applied,
      as well as the nature of the SA output for a given case, will depend on whether
      transport across the air/water interface is handled using the net flux F
      convention or using the individual fluxes J convention. Four hypothetical stream
      cases involving acetone, methyl-tert-butyl ether (MTBE), benzene, chloroform, and
      perchloroethylene (PCE) are considered. Acetone and MTBE are sufficiently water
      soluble from air for a domestic atmospheric source to be capable of yielding c(w)
      values approaching the common water quality guideline range of 1 to 10 microg/L.
      For most other VOCs, such levels cause net outgassing (F > 0). When F > 0 in a
      given section of stream, in the net flux convention, all of the alpha(j) for the
      compound remain unchanged over that section while c(w) decreases. A
      characteristic time tau(d) can be calculated to predict when there will be
      differences between SA results obtained by the net flux convention versus the
      individual fluxes convention. Source apportionment modeling provides the
      framework necessary for comparing different strategies for mitigating
      contamination at points of interest along a stream.

PMID- 16629132
TI  - Estimation of soil sorption coefficients of veterinary pharmaceuticals from soil
      properties.
AB  - Environmental exposure assessment of veterinary pharmaceuticals requires
      estimating the sorption to soil. Soil sorption coefficients of three common,
      ionizable, antimicrobial agents (oxytetracycline [OTC], tylosin [TYL], and
      sulfachloropyridazine [SCP]) were studied in relation to the soil properties of
      11 different soils. The soil sorption coefficient at natural pH varied from 950
      to 7,200, 10 to 370, and 0.4 to 35 L/kg for OTC, TYL, and SCP, respectively. The
      variation increased by almost two orders of magnitude for OTC and TYL when pH was
      artificially adjusted. Separate soil properties (pH, organic carbon content, clay
      content, cation-exchange capacity, aluminum oxyhydroxide content, and iron
      oxyhydroxide content) were not able to explain more than half the variation
      observed in soil sorption coefficients. This reflects the complexity of the
      sorbent-sorbate interactions. Partial-least-squares (PLS) models, integrating all
      the soil properties listed above, were able to explain as much as 78% of the
      variation in sorption coefficients. The PLS model was able to predict the
      sorption coefficient with an accuracy of a factor of six. Considering the pH
      dependent speciation, species-specific PLS models were developed. These models
      were able to predict species-specific sorption coefficients with an accuracy of a
      factor of three to four. However, the species-specific sorption models did not
      improve the estimation of sorption coefficients of species mixtures, because
      these models were developed with a reduced data set at standardized aqueous
      concentrations. In conclusion, pragmatic approaches like PLS modeling might be
      suitable to estimate soil sorption for risk assessment purposes.

PMID- 16629133
TI  - Kinetics of adsorption and desorption of some organochlorine compounds on black
      carbon in a sediment.
AB  - Rate constants for adsorption and desorption of four organochlorine compounds on
      black carbon in a sediment were determined from measurements of the rate of
      removal, by gas purge, of the organochlorine compounds as single solutes from a
      water-sediment mixture immediately after addition of the solute to the system.
      The rates of removal fitted to a kinetic scheme based on Langmuir adsorption onto
      two types of sites in black carbon. The first-order rate constants for desorption
      from these sites were comparable to those for slow and very slow desorption from
      sediment. The time needed to reach apparent equilibrium in the experimental
      setup, with 10 g sediment/L water, ranged from 13 to 166 h, depending on the
      sorbate and the adsorption process. These short times to equilibrium suggest no
      need to assume rate-limiting diffusion from and to adsorption sites in this
      sediment. Average Gibbs free energies for adsorption of the four organochlorine
      compounds from the pure solid state were -10 +/- 3 and -20 +/- 3 kJ/mol for low
      energy and high-energy sites, respectively, pointing to two different adsorption
      mechanisms.

PMID- 16629134
TI  - Bioavailability of polycyclic aromatic hydrocarbons from buried shoreline oil
      residues thirteen years after the Exxon Valdez oil spill: a multispecies
      assessment.
AB  - Seven taxa of intertidal plants and animals were sampled at 17 shoreline sites in
      Prince William Sound ([PWS]; AK, USA), that were heavily oiled in 1989 by the
      Exxon Valdez oil spill (EVOS) to determine if polycyclic aromatic hydrocarbons
      (PAH) from buried oil in intertidal sediments are sufficiently bioavailable to
      intertidal prey organisms that they might pose a health risk to populations of
      birds and wildlife that forage on the shore. Buried residues of EVOS oil are
      present in upper and middle intertidal sediments at 16 sites. Lower intertidal (0
      m) sediments contain little oil. Much of the PAH in lower intertidal sediments
      are from combustion sources. Mean tissue total PAH (TPAH) concentrations in
      intertidal clams, mussels, and worms from oiled sites range from 24 to 36 ng/g
      (parts per billion) dry weight; sea lettuce, whelks, hermit crabs, and intertidal
      fish contain lower concentrations. Concentrations of TPAH are similar or slightly
      lower in biota from unoiled reference sites. The low EVOS PAH concentrations
      detected in intertidal biota at oiled shoreline sites indicate that the PAH from
      EVOS oil buried in intertidal sediments at these sites have a low bioavailability
      to intertidal plants and animals. Individual sea otters or shorebirds that
      consumed a diet of intertidal clams and mussels exclusively from the 17 oiled
      shores in 2002 were at low risk of significant health problems. The low
      concentrations of EVOS PAH found in some intertidal organisms at some oiled
      shoreline sites in PWS do not represent a health risk to populations of marine
      birds and mammals that forage in the intertidal zone.

PMID- 16629135
TI  - Toxicity of weathered Exxon Valdez crude oil to pink salmon embryos.
AB  - Research was conducted at the University of Idaho (Moscow, ID, USA) on the
      toxicity of weathered Exxon Valdez crude oil to embryos of pink salmon from 2001
      to 2003 for the purpose of comparing these data with those from the National
      Oceanic and Atmospheric Administration Fisheries Laboratory at Auke Bay (AK,
      USA). Mortality reported at Auke Bay for embryos chronically exposed to very low
      concentrations of aqueous solutions of weathered oil, measured as dissolved
      polycyclic aromatic hydrocarbons (PAHs), was inconsistent with that in other
      published research. Using the Auke Bay experimental design, we found that
      toxicity is not evident in pink salmon embryos until chronic exposure to
      laboratory weathered and naturally weathered oil concentrations exceeding 1,500
      and 2,250 ppm, respectively, representing a total PAH tissue burden in excess of
      7,100 ppb. Effluent hydrocarbons also drop well below concentrations sufficient
      to cause harm over the time frame of a few weeks, regardless of oiling level.
      Resolution of differences with Auke Bay involved the source of contributing
      hydrocarbons. The experimental design did not exclude dispersed oil droplets from
      the aqueous solution; thus, toxicity was not limited to the dissolved hydrocarbon
      fraction. The implications of the present results are discussed regarding the
      toxic risk of weathered oil to pink salmon embryos in streams of Prince William
      Sound (AK, USA).

PMID- 16629136
TI  - Use of carboxylesterase activity to remove pyrethroid-associated toxicity to
      Ceriodaphnia dubia and Hyalella azteca in toxicity identification evaluations.
AB  - Increases in the use and application of pyrethroid insecticides have resulted in
      concern regarding potential effects on aquatic ecosystems. Methods for the
      detection of pyrethroids in receiving waters are required to monitor
      environmental levels of these insecticides. One method employed for the
      identification of causes of toxicity in aquatic samples is the toxicity
      identification evaluation (TIE); however, current TIE protocols do not include
      specific methods for pyrethroid detection. Recent work identified
      carboxylesterase treatment as a useful method for removing/detecting pyrethroid
      associated toxicity. The present study has extended this earlier work and
      examined the ability of carboxylesterase activity to remove permethrin- and
      bifenthrin-associated toxicity to Ceriodaphnia dubia and Hyalella azteca in a
      variety of matrices, including laboratory water, Sacramento River (CA, USA)
      water, and Salinas River (CA, USA) interstitial water. Esterase activity
      successfully removed 1,000 ng/L of permethrin-associated toxicity and 600 ng/L of
      bifenthrin-associated toxicity to C. dubia in Sacramento River water. In
      interstitial water, 200 ng/L of permethrin-associated toxicity and 60 ng/L of
      bifenthrin-associated toxicity to H. azteca were removed. The selectivity of the
      method was validated using heat-inactivated enzyme and bovine serum albumin,
      demonstrating that catalytically active esterase is required. Further studies
      showed that the enzyme is not significantly inhibited by metals. Matrix effects
      on esterase activity were examined with municipal effluent and seawater in
      addition to the matrices discussed above. Results confirmed that the esterase
      retains catalytic function in a diverse array of matrices, suggesting that this
      technique can be adapted to a variety of aquatic samples. These data demonstrate
      the utility of carboxylesterase treatment as a viable step to detect the presence
      of pyrethroids in receiving waters.

PMID- 16629137
TI  - Comparative toxicity of fluoranthene and pentachlorobenzene to three freshwater
      invertebrates.
AB  - This study examined the temporal component of pentachlorobenzene lethal body
      residues among three freshwater invertebrates. Also, using previous fluoranthene
      data allowed a more detailed examination of the role of biotransformation in
      lethal body residues and comparisons of lethal residues across chemical classes.
      Time-dependent toxicity of fluoranthene and pentachlorobenzene were compared
      among Hyalella azteca, Chironomus tentans, and Diporeia spp. Lethal body residues
      required for 50% mortality (LR50) were not constant and decreased with exposure
      time for all species. Fluoranthene was most toxic to C. tentans with LR50 values
      of 0.38 micromol x g(-1) at 2 d to 0.15 micromol x g(-1) at 10 d and least toxic
      to Diporeia spp. with values of 9.97 micromol x g(-1) at 10 d to 3.67 micromol x
      g(-1) at 28 d. The LR50 values for H. azteca were intermediate and ranged from
      2.25 micromol x g(-1) at 5 d to 0.56 micromol x g(-1) at 28 d. Pentachlorobenzene
      LR50 values were less variable among species and ranged from 1.20 micromol x g(
      1) at 4 d to 0.81 micromol x g(-1) at 10 d for C. tentans, 5.0 micromol x g(-1)
      at 20 d and 2.75 micromol x g(-1) at 28 d for Diporeia spp., and 1.51 micromol x
      g(-1) at 4 d and 0.71 micromol x g(-1) at 28 d for H. azteca. When LR50 values
      for fluoranthene and pentachlorobenzene were compared at steady state, the lethal
      residues for the amphipod species were within the range expected for nonpolar
      narcotic chemicals (anesthetics); however, C. tentans was more sensitive to
      fluoranthene than pentachlorobenzene, confirming our previous hypothesis that
      biotransformation of fluoranthene likely produces a metabolite(s) acting by some
      specific mechanism of action. The information collected from this study allows a
      greater understanding of residue-response relationships, specifically relative
      species sensitivities.

PMID- 16629138
TI  - Role of sediment organic matter quality and feeding history in dietary absorption
      and accumulation of pyrene in the mud snail (Hydrobia ulvae).
AB  - Organic matter (OM) input to marine sediments varies seasonally both in quantity
      and quality. Because sedimentary OM (SOM) constitutes food for many benthic
      organisms, its properties should affect the dietary uptake of sediment-associated
      contaminants. We explored the effect of SOM quality/food value on short- and long
      term pyrene accumulation in the mud snail (Hydrobia ulvae) and performed dual
      tracer pulse-chase experiments to investigate the feeding mechanisms driving
      dietary pyrene uptake. The quality of the SOM was manipulated by enriching
      sediments either with high-quality microalgae or low-quality lignin, adding equal
      amounts of total organic carbon. Long- and short-term bioaccumulation increased
      with increasing SOM quality, as did pyrene ingestion rate (IR(pyr)), which also
      was affected by feeding history. By feeding selectively, snails concentrated
      pyrene 10-fold in ingested compared to ambient sediment, independent of SOM
      quality. Average pyrene absorption efficiency (AE(pyr): -65%) varied inversely
      with SOM quality and IR(pyr). Both AE(pyr) and gut passage time (alpha 1/IR(pyr))
      agreed with theoretical models incorporating the time-dependence of absorption
      efficiency. Thus, SOM quality moderates dietary contaminant uptake in deposit
      feeders, and in H. ulvae, this occurs via OM-induced alterations of ingestion
      rate. Consequently, enhanced sediment-associated contaminant uptake is predicted
      for deposit feeders following phytoplankton blooms, principally because of OM
      quality-driven increases in the ingestion rate.

PMID- 16629139
TI  - Congener-specific toxicokinetics of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in black
      eared kites (Milvus migrans): cytochrome P4501A-dependent hepatic sequestration.
AB  - Concentrations of dioxins and related compounds (DRCs), such as polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar
      polychlorinated biphenyls (Co-PCBs), were determined in black-eared kites (BEKs;
      Milvus migrans) collected from the Kanto district in Japan. Total 2,3,7,8-tetra
      CDD toxic equivalents (TEQs) were in the range of 99 to 3,800 pg/g lipid weight
      in the liver and 42 to 760 pg/g lipid weight in the pectoral muscle. Three
      congeners, including PCB 126, 2,3,4,7,8-penta-CDF, and 1,2,3,7,8-penta-CDD, made
      a greater contribution to total TEQs in both tissues. Levels of ethoxyresorufin-O
      deethylase activity and a cross-reactive protein with anti-rat cytochrome P4501A
      (CYP1A) polyclonal antibodies showed no significant correlation with hepatic
      TEQs. This may be attributed to low sensitivity and insufficient TEQ levels to
      cause CYP1A induction, high metabolic potential of a series of congeners, and
      influence of CYP1A inducers other than DRCs. Most of the PCDD/ Fs and non-ortho
      Co-PCBs exhibited a total TEQ- and CYP1A-dependent increase in the liver to
      muscle concentration ratios, implying their concentration-dependent hepatic
      sequestration in which CYP1A was involved. Comparison of the toxicokinetics in
      avian species revealed that BEKs possibly have higher potentials than common
      cormorants for metabolizing and sequestering certain congeners in the liver in
      terms of hepatic concentration profiles and liver:muscle concentration ratios,
      respectively. These results clearly indicate that the toxicokinetics of DRCs is
      congener-, tissue-, and species-specific as well as concentration-dependent.
      Therefore, CYP1A expression is one of the critical factors that determine the
      toxicokinetics in wild avian species.

PMID- 16629140
TI  - Bioaccumulation and trophic transfer of polychlorinated biphenyls by aquatic and
      terrestrial insects to tree swallows (Tachycineta bicolor).
AB  - Insectivorous passerines often bioaccumulate polychlorinated biphenyls (PCBs) via
      trophic transfer processes. Tree swallows (Tachycineta bicolor) frequently are
      used for estimating PCB bioaccumulation, yet the focus on specific trophic links
      between contaminated sediment and bird has been limited. Bioaccumulation of PCBs
      from sediment to tree swallows was examined with focus on trophic pathways by
      simultaneously examining PCBs in emergent aquatic and terrestrial insects and gut
      contents of nestlings. Total PCB concentrations increased from sediment (123.65
      +/- 15.93 microg/kg) to tree swallow nestlings (2,827.76 +/- 505.67 microg/kg),
      with emergent aquatic insects, terrestrial insects, and gut content samples
      having intermediate concentrations. Biota-sediment accumulation factors (BSAFs)
      varied among congeners for tree swallow nestlings and for male and female
      Chironomus spp. For nestlings, the highest BSAF was for the mono-ortho
      substituted congener 118. Nestling biomagnification values were similar for gut
      contents and female Chironomus spp., suggesting this diet item may be the main
      contributor to the overall PCB transfer to nestlings. However, gut content
      samples were highly variable and, on a PCB congener pattern basis, may have been
      influenced by other taxa, such as terrestrial insects. Considering dietary
      plasticity of many insectivorous birds, the present study suggests that a variety
      of potential food items should be considered when examining PCB accumulation in
      insectivorous passerines.

PMID- 16629141
TI  - Elevated fluctuating asymmetry in eastern mosquitofish (Gambusia holbrooki) from
      a river receiving paper mill effluent.
AB  - The present study investigated whether fluctuating asymmetry can serve as a
      useful biomarker of environmental stress in the eastern mosquitofish (Gambusia
      holbrooki). Fluctuating asymmetry was measured in sexually mature females sampled
      from two Florida, USA, coastal streams: The Fenholloway River, which is dominated
      by effluent from a paper mill, and Spring Creek, a tributary to the Fenholloway
      River (Taylor County, FL, USA) that does not receive paper mill effluent. Nine
      morphometric (lengths of the A and B scales, fifth pectoral fin ray, supraorbital
      canal, and preorbital canal and the sixth gill raker on the first brachial arch;
      orbit diameter; distance from the dorsal-ventral midpoint of the eye socket to
      the base of the pectoral fin; and distance from the postorbital canal to the
      operculum) and five meristic traits (numbers of scales in the lateral line, radii
      on the A and B scales, pectoral fin rays, and gill rakers on the first brachial
      arch) were included. For each of the three indexes of fluctuating asymmetry that
      were used, the majority of the traits showed a higher level of fluctuating
      asymmetry in fish from the Fenholloway River than in fish from Spring Creek. For
      two of the indexes, the difference was significant. Comparisons of mean values
      for fluctuating asymmetry (over all traits) for each fish and the means of a
      composite index of asymmetry both indicated that fish from the Fenholloway River
      had significantly greater overall fluctuating asymmetry than those from Spring
      Creek. Results of the present study are consistent with the hypothesis that
      environmental stress increased the level of fluctuating asymmetry in fish from
      the Fenholloway River. Thus, fluctuating asymmetry appears to be a useful
      biomarker for stress-induced developmental instability in the eastern
      mosquitofish.

PMID- 16629142
TI  - Metal trophic transfer from algae to cladocerans and the relative importance of
      dietary metal exposure.
AB  - We initially investigated effects and uptake of cadmium and copper on
      Pseudokirchneriella subcapitata (primary producer; formerly known as Selenastrum
      capricornutum). Our major efforts focused on the effects of metal-laden (i.e.,
      Cd, Cu) P. subcapitata when used to provide dietary metal exposure to
      Ceriodaphnia dubia (primary consumer). Major test endpoints included feeding
      rate, survival, and reproduction. Metal body burden in C. dubia increased dose
      dependently at dietary exposure concentrations of 0.6 microg/g algal dry weight
      or less for cadmium and 74.7 microg/g algal dry weight or less for copper.
      However, it decreased sharply when dietary concentrations exceeded 0.6 microg/g
      algal dry weight for cadmium and 74.7 microg/g algal dry weight copper. Both
      dietary cadmium and copper affected all the major test endpoints. Whereas
      reproduction was observed to be the most sensitive endpoint, survival was
      observed to be the least sensitive endpoint. These results demonstrated the
      potential importance of dietary exposure for consideration in metal regulations
      or risk assessment.

PMID- 16629143
TI  - Influence of metal exposure history on the bioaccumulation and subcellular
      distribution of aqueous cadmium in the insect Hydropsyche californica.
AB  - The influence of metal exposure history on rates of aqueous Cd accumulation,
      elimination, and subcellular distribution was examined in the aquatic insect
      Hydropsyche californica. Specimens were obtained from a reference site and a
      metal-contaminated site and returned to the laboratory where they were
      continuously exposed to aqueous Cd (518 ng/L, nominal) for 6 d, followed by 9 d
      of depuration. Rates of Cd accumulation and elimination were similar in insects
      from the two sites. Efflux rate constants, k((e), ranged from 0.20 to 0.24/d (t
      1/2 approximately 3 d). Immediately following exposure, the cytosol accounted for
      40% of the body burden in insects from both sites; however, 89 +/- 2% of the
      cytosolic Cd was associated with metallothionein-like proteins (MTLP) in insects
      from the contaminated site, compared to 60 +/- 0% in insects from the reference
      site. The concentration of Cd bound to non-MTLPs (representing potentially Cd
      sensitive proteins) was significantly greater in the insects from the reference
      site (134 +/- 7 ng/g) than in those from the contaminated site (42 +/- 2 ng/g).
      At the end of the depuration period, 90% of the accumulated Cd body burden had
      been eliminated, and Cd concentrations in MTLPs and non-MTLPs were similar
      between the sites. Results suggested that differences in exposure history had no
      influence on the bioaccumulation of Cd, but did affect the concentrations of Cd
      bound to MTLP during Cd exposure in these insects.

PMID- 16629144
TI  - Thyroid function and reproductive success in rodents exposed to perchlorate via
      food and water.
AB  - The purpose of the present study was to determine if exposure to perchlorate via
      food items would have effects on mammals similar to those caused by exposure
      through drinking water at approximately equivalent doses. Prairie voles (Microtus
      ochrogaster) and deer mice (Peromyscus maniculatus) were used to assess the
      potential toxicity of perchlorate-contaminated food items. Voles and mice were
      divided randomly into three treatment groups--perchlorate-contaminated food
      (PCF), perchlorate-contaminated water (PCW), and control groups--such that each
      treatment group contained equal numbers of males and females. Rodents in PCF
      treatment groups were fed chow formulated with soybean plant matter that had been
      grown with perchlorate-contaminated irrigation water. Individuals in the control
      and PCF groups were provided distilled/deionized drinking water, whereas the PCW
      group received drinking water containing sodium perchlorate. Only slight
      differences among treatment groups were observed in a variety of endpoints,
      including reproductive success, tissue perchlorate concentrations, thyroid
      hormone concentrations, and thyroid histology. However, trends observed in the
      present study suggest that perchlorate exposure via water may result in slightly
      greater effects than exposure to perchlorate via food. These data and recent
      reports of perchlorate in a wide variety of food items indicate that exposure via
      food intake is an important consideration when examining cumulative risk among
      humans, livestock, and wildlife.

PMID- 16629145
TI  - Contribution of ammonium ions to the lethality and antimetamorphic effects of
      ammonium perchlorate.
AB  - Ammonium perchlorate (AP) is a widespread military waste product in the United
      States and is a potent thyroid function disruptor in all vertebrates tested thus
      far. To determine the relative contribution of ammonium ions to the toxicity of
      AP, we exposed embryonic and larval Xenopus laevis to various concentrations of
      sodium perchlorate (SP) or ammonium chloride (AC). Ammonium perchlorate was
      significantly more lethal than SP; 5-d LC50s were 83 and 2,780 mg/L,
      respectively. To determine whether ammonium ions contribute to the antithyroid
      effects of AP, we exposed embryonic and larval X. laevis to two sublethal,
      environmentally relevant concentrations of AP or identical concentrations of AC
      or SP. At the smaller concentration, only AP delayed metamorphosis and reduced
      hindlimb growth. Sodium perchlorate and AP, but not AC, prevented metamorphosis
      and reduced hindlimb growth at the greater concentration. Although AP was
      slightly more effective in reducing outward manifestations of thyroid disruption,
      both perchlorate salts, unlike AC, caused profound histopathologic changes in the
      thyroid. Exposure to the higher concentration of either perchlorate salt produced
      a feminizing effect, resulting in a skewed sex ratio. We conclude that ammonium
      ions contribute significantly to the toxicity of AP but not to the direct
      antithyroid effects of perchlorate.

PMID- 16629146
TI  - Trophic transfer and biotransformation of polychlorinated biphenyls in zebra
      mussel, round goby, and smallmouth bass in Lake Erie, USA.
AB  - Trophic transfer of polychlorinated biphenyl (PCB) congeners in zebra mussels
      (Dreissena polymorpha), round gobies (Neogobius melanstomus), and smallmouth bass
      (Micropterus dolomieu) were assessed in four sites along the south shore of the
      west and central basin of Lake Erie (all sites were in OH, USA). Total PCB levels
      in smallmouth bass (1,091-1,520 ng/g wet weight) and round gobies (118-256 ng/g
      wet weight) were similar among sites despite a west-to-east decrease in total PCB
      concentrations in zebra mussels (29-97 ng/g wet weight). At all sites, PCB body
      burden increased three- to fivefold at each successive trophic level, suggesting
      biomagnification in this nonnative food chain. Whereas fish species were
      dominated by the hexachlorine homologue, zebra mussels were dominated by penta-
      and hexachlorine homologues; the average degree of chlorination of PCBs was 56.1%
      for zebra mussels, 60.4% for round goby, and 59.9% for smallmouth bass bodies.
      Predictive structure-activity relationships based on chemical characteristics,
      such as the octanol-water partition coefficient (log K(ow)), had little
      predictive power on bioaccumulation and biotransformation of PCB congeners
      because of nonlinearity, threshold relationships, and species-specific
      differences. Calculated trophic transfer for the smallmouth bass-round goby
      linkage was higher than for the round goby-zebra mussel linkage. Only when PCB
      congeners were grouped by chemical structure first (vicinal [adjacent] H-atom
      position in the phenyl ring) were linear relationships achieved. It appeared that
      the chemical group to which each congener belonged influenced biotransformation
      more than species-specific (round gobies vs smallmouth bass) differences. Biotic
      changes at midtrophic levels, such as exotic species invasions, may have an
      increasingly important role in determining pollutant cycling and hence pollutant
      residues in top predators.

PMID- 16629147
TI  - Photoinduced toxicity of polycyclic aromatic hydrocarbons to Daphnia magna:
      ultraviolet-mediated effects and the toxicity of polycyclic aromatic hydrocarbon
      photoproducts.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants
      known for their photoinduced toxicity. This toxicity may occur through two
      mechanisms: Photosensitization, and photomodification. Photosensitization
      generally leads to the production of singlet oxygen, a reactive oxygen species
      that is highly damaging to biological molecules. Photomodification of PAHs,
      usually via oxidation, results in the formation of new compounds and can occur
      under environmentally relevant levels of actinic radiation. The toxicities of 16
      intact PAHs to Daphnia magna were assessed under two ultraviolet radiation
      conditions. The toxicity of intact PAHs generally increased in the presence of
      full-spectrum simulated solar radiation relative to that in the presence of
      visible light plus ultraviolet A only. Despite the knowledge of a bipartite
      mechanism of phototoxicity that includes photosensitization and
      photomodification, few studies have examined the effects of PAH photoproducts on
      animals. To expand the existing data, 14 PAH photoproducts (oxy-PAHs) also were
      assayed, most of which were highly toxic without further photomodification. Two
      photoproducts of benzo[a]pyrene, 1,6- and 3,6-benzo[a]pyrenequinone, were the
      most toxic compounds tested, followed closely by benz[a]anthraquinone. Each of
      these three compounds had a median effective concentration in the low nanomolar
      range. The data presented highlight the effects of ultraviolet radiation on
      mediating PAH toxicity and the need to analyze absorption spectra of contaminants
      in the prediction of photoinduced toxicity. The importance of the role of
      photomodification also is stressed, because several oxy-PAHs, an unregulated
      group of contaminants, were highly toxic to D. magna, a key bioindicator species
      in aquatic ecosystems.

PMID- 16629148
TI  - Body residues as dose for sublethal responses in alevins of landlocked salmon
      (Salmo salar m. sebago): a direct calorimetry study.
AB  - Questions of organism-specific factors, toxicity endpoints, and their relation to
      mode-of-action all are related to consistency and applicability of body residue
      based approaches. To address this issue, direct calorimetry was used to evaluate
      metabolic responses of alevins of landlocked salmon (Salmo salar m. sebago) to
      pentachlorophenol (PCP) exposure ranging from 0 to 1.04 microM for 24 h or 24,
      48, and 72 h (0, 0.26, and 0.55 microM, respectively). The body residues were
      used as a dose metric for sublethal responses. The body size, rapid ontogenetic
      development, and exposure to a specific pollutant all were heat output-modifying
      factors. The acute exposure (24-72 h) to PCP led to a heat output-enhancing
      effect, which directly was related to an internal concentration of PCP in the
      range of 0.01 to 0.15 micromol/g. Within the treatments, body size per level of
      metabolic rate and magnitude of physiological response were not correlated, thus
      the alevins with higher mass-specific metabolic rate were not more sensitive to
      PCP. Primarily, increasing metabolic rate during posthatch development controls
      PCP toxicity only by affecting bioaccumulation kinetics, not the toxic potency of
      the chemical. New information of a relationship between observed natural
      variation in measured physiological trait of fish and PCP-induced response and
      its body residue-based level is of ecotoxicological importance.

PMID- 16629149
TI  - Predicted effects of toxicant mixtures are confirmed by changes in fish species
      assemblages in Ohio, USA, rivers.
AB  - The purposes of this study were to investigate whether exposure to toxicant
      mixtures is associated with fish assemblage characteristics in the field and to
      describe the relationships between predicted chronic and acute mixture risks and
      observed impacts. Fish abundance and abiotic monitoring data from Ohio, USA,
      surface waters were compiled and analyzed. Variability of biotic and abiotic
      parameters was large. Exposure assessment, risk assessment with species
      sensitivity distributions, and mixture toxicity rules were used to calculate a
      relative risk predictor: The multisubstance potentially affected fraction of
      species (msPAF). Predicted acute and chronic risks ranged from low values to more
      than 10 and 50% of species potentially affected, respectively. Pearson
      correlations between predicted risk and observed assemblage characteristics were
      nonsignificant for total abundance, number of species, Shannon-Weaver index, and
      evenness. Moderately significant correlations were found between predicted risk
      and abundance for 23% of individual species. Both abundance increases and
      decreases were observed. Generalized linear model (GLM) regressions revealed
      significant nonlinear associations between predicted risk and the abundance for
      50% (metals and ammonia) and 55% (household product ingredients) of the species.
      Local ecological impact was expressed as the fraction of species expected but not
      observed, both with and without attribution of impact to mixture exposure. The
      association between predicted impacted fraction and the fraction of species
      expected but not observed was not significant. Predicted acute and chronic
      impacted fractions were associated significantly with the observed fraction of
      species likely lost by the action of toxicant mixtures under field conditions,
      with wide confidence bounds. These findings confirm the view that higher mixture
      impacts are expected in the field at higher msPAF.

PMID- 16629150
TI  - An algal probe for copper speciation in marine waters: laboratory method
      development.
AB  - Laboratory-based algal assays were developed to explore the bioavailability of
      copper to the marine alga Thalassiosira weissflogii. A calibration strategy was
      developed that avoided use of the synthetic ligand ethylenediaminetetraacetic
      acid (EDTA) in the Aquil growth medium, thereby allowing ambient metal
      speciation. In a comparison of T. weissflogii cells grown in Aquil medium with
      EDTA to medium containing no added copper, zinc, and less than 0.003 nM of EDTA,
      no significant growth differences were observed after 8 d, indicating adequate
      stored nutrients. A 30-h assay was selected as the optimal time frame after
      examination of data from concentration-response experiments. Using 65Cu stable
      isotope additions, parameters examined included growth, chlorophyll a, copper
      uptake, phytochelatin production, and dissolved organic carbon excretion. The T.
      weissflogii specific growth rates decreased from 1.36 d(-1)( at pCu (i.e., the
      negative logarithmic concentration of free Cu) = 8.8 to 0.56 d(-1) at pCu = 7.8,
      whereas intercellular copper concentrations increased from 13.6 to 70.1 fg/cell,
      respectively. Calculated values of the copper concentration that caused a 50%
      reduction in algal growth of pCu = 7.7 and copper per algal mass of 625 microg/g
      were established. Using an algal assay based on EDTA-free culture medium, along
      with trace-metal clean techniques, the effect of copper on T. weissflogii and the
      speciation of copper in marine waters can be studied.

PMID- 16629151
TI  - Biochemical and histopathological effects in pearl dace (Margariscus margarita)
      chronically exposed to a synthetic estrogen in a whole lake experiment.
AB  - Potential effects of exposure to the synthetic estrogen 17alpha-ethynylestradiol
      (EE2) were examined in several species of fish from a lake experimentally treated
      with environmentally relevant concentrations of the contaminant. Ethynylestradiol
      was added to Lake 260, a small Precambrian shield lake at the Experimental Lakes
      Area in northwestern Ontario, Canada, from May to October of 2001, 2002, and
      2003. Mean concentrations of EE2 in epilimnetic waters ranged between 4.5 and 8.1
      ng/L during the three years, with overall means of 6.1 (+/- 2.8), 5.0 (+/- 1.8),
      and 4.8 (+/- 1.0) ng/L for the three years, respectively. Male and female pearl
      dace (Margariscus margarita) captured after EE2 additions began contained up to
      4,000-fold higher concentrations of the egg yolk precursor vitellogenin than fish
      captured from the same lake before the EE2 additions or when compared to fish
      from reference lakes. Edema in the ovaries, inhibited development of testicular
      tissue, intersex, and histopathological kidney lesions were all evident in fish
      exposed to EE2. Some indications that EE2 exposure affected in vitro
      steroidogenic capacity of the ovaries and the testes existed, although results
      were not always consistent between years. Pearl dace abundance was similar in the
      lake treated with EE2 and the reference lake. A trend exists toward a reduced
      overall population of pearl dace from the treated and reference lakes, as do
      indications that young-of-the-year size classes are less abundant in the EE2
      treated lake. Biochemical and histopathological impacts observed in fish exposed
      to EE2 in this study have not yet been linked to clear population level impacts
      in pearl dace. Monitoring of these populations is ongoing.

PMID- 16629152
TI  - Reproductive effects of the endocrine disruptor fenarimol on a Baltic amphipod
      Monoporeia affinis.
AB  - An endocrine disruptor, the fungicide fenarimol, was investigated regarding its
      effects on reproduction and hormone (ecdysteroid) levels in the deposit-feeding
      amphipod Monoporeia affinis. In addition, the influence of food shortage, both by
      itself and in combination with fenarimol, on reproduction was examined. Field
      collected amphipods were exposed in flow-through microcosms during the period of
      sexual maturation and mating in four treatment series: Control with low food,
      fenarimol with low food, control with high food, and fenarimol with high food.
      Fenarimol was added at a concentration of 0.3 mg/L in two pulses/ week. Results
      show that fenarimol has a negative effect on fertilization rate and male mating
      ability. Results were supported by a tendency toward delayed male sexual
      development. Food shortage decreased weight in both sexes and retarded female
      oocyte development. Higher ecdysteroid levels were recorded in males than in
      females, and food shortage increased male ecdysteroid levels. No effect of
      fenarimol exposure on ecdysteroid levels was observed. No synergistic effects of
      fenarimol and food shortage could be distinguished in any variable examined.
      Thus, M. affinis was vulnerable to reproductive impairment by fenarimol, with
      effects on the next generation (i.e., a disturbed sexual development and
      fertilization ability). Food shortage has negative effects on M. affinis, but it
      does not enhance the effects of fenarimol.

PMID- 16629153
TI  - Daphnia magna mortality when exposed to titanium dioxide and fullerene (C60)
      nanoparticles.
AB  - Nanoparticles (1-100 nm) comprise the latest technological advances designed to
      do everything from absorb environmental toxins to deliver drugs to a target
      organ. Recently, however, they have come under scrutiny for the potential to
      cause environmental damage. Because compounds in this miniature size range have
      chemical properties that differ from those of their larger counterparts,
      nanoparticles deserve special attention. Our main objective was to assess the
      potential impact that nanoparticles may have on release into aquatic
      environments. We prepared titanium dioxide (TiO2) and fullerene (C60)
      nanoparticles by filtration in tetrahydrofuran or by sonication. Daphnia magna
      were exposed to the four solutions using U.S. Environmental Protection Agency 48
      h acute toxicity tests. Images of the particle solutions were recorded using
      transmission-electron microscopy, and the median lethal concentration, lowest
      observable-effect concentration, and no-observable-effect concentration were
      determined. Exposure to filtered C60 and filtered TiO2 caused an increase in
      mortality with an increase in concentration, whereas fullerenes show higher
      levels of toxicity at lower concentrations. Exposure to the sonicated solutions
      caused varied mortality. Understanding the potential impacts of nanoparticles
      will help to identify the most appropriate nanotechnology to preserve the aquatic
      environment while advancing medical and environmental technology.

PMID- 16629154
TI  - Mercury fractionation, bioavailability, and ecotoxicity in highly contaminated
      soils from chlor-alkali plants.
AB  - Mercury (Hg) fractionation, speciation, bioavailability, and ecotoxicity were
      investigated in three highly contaminated soils from chlor-alkali plants. Single
      extractions and a validated four-step sequential extraction scheme were used.
      Total, volatile, and methyl-Hg concentrations were determined. Mercury was then
      separated in fractions defined as water-soluble (F1), exchangeable (F2), organic
      (F3), and residual (F4). Germination and growth inhibition of barley (Hordeum
      vulgare) and mortality of earthworms (Eisenia andrei) were assessed, and tissue
      Hg concentrations of exposed organisms were determined. Results revealed highly
      (295 +/- 18-11,500 +/- 500 microg Hg/g) contaminated soils, but extracted
      fractions indicated relatively low mobility of Hg. Nevertheless, the water
      soluble and the CaCl2-extractable fractions represented significant Hg
      concentrations (299 +/- 18 microg/g in soil 3, 67.4 +/- 2.3 microg/g in soil 1,
      and 9.5 +/- 0.3 microg/g in soil 2), and volatile Hg ranged between 14 and 98% of
      total Hg. Overall, Hg concentrations reached 6,560 +/- 240 microg/g in roots,
      4,200 +/- 1,070 microg/g in aerial plants, and 1,410 +/- 120 microg/g in E.
      andrei. Earthworm mortality was 100% after exposure to the soil with the highest
      concentration of mobile Hg. In the latter soil, earthworm fragmentation and
      chlorotic plants were observed. Bioconcentration factors (BCFs) were higher in
      barley compared to earthworms, but BCFs yielded misleading values after exposure
      to the extremely contaminated soil. This study shows that Hg accumulated
      primarily in the roots, but results also indicate uptake of gaseous Hg by the
      aerial plants of barley. Tissue-Hg concentrations of both exposed organisms were
      correlated with water-soluble and CaCl2-extractable Hg, and growth inhibition was
      in agreement with Hg fractionation.

PMID- 16629155
TI  - A meta-analysis comparing the toxicity of sediments in the laboratory and in
      situ.
AB  - Sediment toxicity tests in the laboratory are an important part of ecological
      risk assessments, yet how they relate to sediment toxicity in situ has rarely
      been explored. Using meta-analysis, we examined differences in the toxicity of
      sediment tested in the laboratory and in situ. Data from four published studies
      were subjected to rigorous statistical analyses. Overall, the toxicity of
      sediments in laboratory tests was substantially less than their toxicity in situ.
      Differences between laboratory and in situ toxicity, expressed using the log odds
      ratio effect size, varied significantly among published studies. Effect size
      increased significantly with increasing sediment toxicity, showing that the more
      toxic the sediment, the greater the disparity between laboratory and field
      toxicities. Our findings may not apply to all laboratory/field comparisons;
      however, we consider that the overlying water in field situations is a
      significant contributor to this relationship through additional contamination and
      toxicity. Our findings also have important implications for the use of laboratory
      tests to assess improvements in sediment quality and remediation, because changes
      in laboratory toxicity may not reflect the true improvements to sediment quality
      in situ.

PMID- 16629156
TI  - Relationships between T-cell-mediated immune response and Pb, Zn, Cu, Cd, and as
      concentrations in blood of nestling white storks (Ciconia ciconia) and black
      kites (Milvus migrans) from Donana (southwestern Spain) after the Aznalcollar
      toxic spill.
AB  - In the Aznalcollar mining accident (April 1998), nearly six million cubic meters
      of toxic wastes were spilled in the surroundings of the Donana National Park
      (southwestern Spain). The present study focused on the likely effects of metal
      pollution on the immune system of nestling white storks (Ciconia ciconia) and
      black kites (Milvus migrans) sampled in the nearby area. Using the
      phytohaemagglutinin skin test, we examined cell-mediated immune response (CMI) in
      relation to Pb, Zn, Cu, Cd, and As concentrations in blood of 281 nestling white
      storks and of 89 black kites. The former species was monitored along a four-year
      period (1999, 2001-2003), while black kites were sampled in 1999. Overall,
      average levels of heavy metals and As were relatively low when compared to those
      reported for birds in metal-polluted areas. Copper showed a negative effect on
      CMI in both species, although the relationship was significant only for white
      storks in 2002. We found no evidence that environmental exposure to Pb, Zn, As,
      and Cd had any effect on nestlings' CMI. Interannual consistency is revealed as
      an important factor, supporting the need of long-term studies when assessing the
      immunotoxic effects of metal exposure in the wild.

PMID- 16629157
TI  - Evidence of pesticide impacts in the Santa Maria River watershed, California,
      USA.
AB  - The Santa Maria River provides significant freshwater and coastal habitat in a
      semiarid region of central California, USA. We conducted a water and sediment
      quality assessment consisting of chemical analyses, toxicity tests, toxicity
      identification evaluations, and macroinvertebrate bioassessments of samples from
      six stations collected during four surveys conducted between July 2002 and May
      2003. Santa Maria River water samples collected downstream of Orcutt Creek (Santa
      Maria, Santa Barbara County, CA, USA), which conveys agriculture drain water,
      were acutely toxic to cladocera (Ceriodaphnia dubia), as were samples from Orcutt
      Creek. Toxicity identification evaluations (TIEs) suggested that toxicity to C.
      dubia in Orcutt Creek and the Santa Maria River was due to chlorpyrifos.
      Sediments from these two stations also were acutely toxic to the amphipod
      Hyalella azteca, a resident invertebrate. The TIEs conducted on sediment
      suggested that toxicity to amphipods, in part, was due to organophosphate
      pesticides. Concentrations of chlorpyrifos in pore water sometimes exceeded the
      10-d median lethal concentration for H. azteca. Additional TIE and chemical
      evidence suggested sediment toxicity also partly could be due to pyrethroid
      pesticides. Relative to an upstream reference station, macroinvertebrate
      community structure was impacted in Orcutt Creek and in the Santa Maria River
      downstream of the Creek input. This study suggests that pesticide pollution
      likely is the cause of ecological damage in the Santa Maria River.

PMID- 16629158
TI  - A perspective on the environmental risk of halogenated by-products from uses of
      hypochlorite using a whole effluent toxicity based approach.
AB  - An assessment has been made of the potential for toxic effects to aquatic life
      that may arise from halogenated organic by-products formed by reaction of
      hypochlorite with organic matter in various use scenarios as a contribution to
      the risk assessment of sodium hypochlorite under the European Union Existing
      Chemicals legislation. In the study, samples that would represent worst-case
      models for effluents containing halogenated by-products from a range of uses of
      hypochlorite were prepared by chlorinating and then dechlorinating (removing
      residual chlorine) raw settled sewage (C/D-RSS). This sample was then compared to
      raw settled sewage that had not been treated (RSS) to assess whether halogenated
      by-products formed in the chlorination process were toxic or bioaccumulable and
      persistent. The relative toxicity of the samples was assessed using a series of
      tests with representatives of different taxonomic groups (bacteria, algae, and
      invertebrates). The persistence and potential for bioaccumulation of chlorinated
      by-products was assessed by exposing solid-phase microextraction fibers to
      samples of RSS and C/D-RSS before and after degradation in a Zahn-Wellens test.
      For all the taxa tested in the study, the mixture of by-products formed in the
      C/D-RSS sample did not increase toxicity relative to that measured in the RSS
      sample. Chlorination of the raw settled sewage did produce additional potentially
      bioaccumulable halogenated substances compared to the raw settled sewage.
      However, after degradation, the amount of potentially bioaccumulable halogenated
      substances in the RSS and C/D-RSS samples was comparable, indicating that these
      substances were degradable. The results are discussed in the context of the
      overall risk assessment for sodium hypochlorite.

PMID- 16629159
TI  - Virtual screening for environmental pollutants: structure-activity relationships
      applied to a database of industrial chemicals.
AB  - The current risk paradigm calls for individual consideration and evaluation of
      each separate environmental pollutant, but this does not reflect accurately the
      cumulative impact of anthropogenic chemicals. In the present study, previously
      validated structure-activity relationships were used to estimate simultaneously
      the baseline toxicity and atmospheric persistence of approximately 50,000
      compounds. The results from this virtual screening indicate fairly stable
      statistical distributions among small anthropogenic compounds. The baseline
      toxicity was not changed much by halogen substitution, but a distinct increase
      seemed to occur in the environmental persistence with increased halogenation. The
      ratio of the atmospheric half-lives to the median lethal concentrations provides
      a continuous scale with which to rank and summarize the incremental environmental
      impacts in a mixture-exposure situation. Halogenated compounds as a group
      obtained a high ranking in this data set, with well-known pollutants at the very
      top: DDT metabolites and derivatives, polychlorinated biphenyls, diphenyl ethers
      and dibenzofurans, chlorinated paraffins, chlorinated benzenes and derivatives,
      hydrochlorofluorocarbons, and dichlorononylphenol. Environmentally friendly
      chemicals that obtained the lowest rank are nearly all hydroxylated and water
      soluble. Virtual screening can assist with "green chemistry" in designing safe
      and degradable products and enable assessment of the efficiency in chemicals risk
      management.

PMID- 16629160
TI  - Compensatory responses induced by oxidative stress in Alzheimer disease.
AB  - Oxidative stress occurs early in the progression of Alzheimer disease,
      significantly before the development of the pathologic hallmarks, neurofibrillary
      tangles and senile plaques. In the first stage of development of the disease,
      amyloid-beta deposition and hyperphosphorylated tau function as compensatory
      responses and downstream adaptations to ensure that neuronal cells do not succumb
      to oxidative damage. These findings suggest that Alzheimer disease is associated
      with a novel balance in oxidant homeostasis.

PMID- 16629161
TI  - Molecular and pathological basis of aceruloplasminemia.
AB  - Aceruloplasminemia is an autosomal recessive neurodegenerative disease
      characterized by iron accumulation in the brain as well as visceral organs. It is
      a loss-of-function disorder caused by mutations in the ceruloplasmin gene.
      Clinically, this disease consists of the triad of adult-onset neurological
      disease, retinal degeneration and diabetes mellitus. Massive iron accumulation
      and extensive loss of neurons are observed in the basal ganglia. The elevated
      iron concentration is associated with increased lipid peroxidation in the brains
      of aceruloplasminemia patients. Enlarged or deformed astrocytes and spheroid-like
      globular structures are characteristic neuropathological findings in
      aceruloplasminemia. Moreover, deformed astrocytes and globular structures react
      positively to anti-4-hydroxynonenal antibody, suggesting that increased oxidative
      stress is involved in neuronal cell death in aceruloplasminemia brain. More than
      30 aceruloplasminemia-causing mutations in the ceruloplasmin gene have been
      identified. We examined the biosynthesis of two missense ceruloplasmin proteins
      that result from a Japanese P177R mutation and a Dutch G631R mutation, using
      Chinese hamster ovary cell expression system. The P177R mutant protein is
      retained in the endoplasmic reticulum. The G631R mutant protein, predicted to
      alter the interactions at a single type I copper-binding site, prevented
      incorporation of copper into apoceruloplasmin and resulted in the synthesis and
      secretion only of apoceruloplasmin. Molecular analysis of missense mutations
      showed different structure-function relationships in ceruloplasmin protein. The
      investigation of mutant ceruloplasmin reveals new insights into molecular
      pathogenesis of aceruloplasminemia as well as biosynthesis, trafficking, and
      function of ceruloplasmin.

PMID- 16629162
TI  - Gene chip analyses reveal differential genetic responses to iron deficiency in
      rat duodenum and jejunum.
AB  - Previous studies revealed novel genetic changes in the duodenal mucosa of iron
      deprived rats during postnatal development. These observations are now extended
      to compare the genetic response to iron deficiency in the duodenum versus jejunum
      of 12-wk-old rats. cRNA samples were prepared from the duodenal and jejunal
      mucosa of three groups each of control and iron-deficient rats and hybridized
      with RAE 230A and 230B gene chips (Affymetrix). Stringent data reduction
      strategies were employed. Results showed that several genes were similarly
      induced in both gut segments, including DMT1, Dcytb, transferrin receptor 1, heme
      oxygenase 1, metallothionein, the Menkes copper ATPase (ATP7A), tripartitie motif
      protein 27, and the sodium-dependent vitamin C transporter. However, a subset of
      genes showed regulation in only one or the other gut segment. In duodenum only,
      gastrokine 1, trefoil factor 1 and claudin 2 were induced by iron-deficiency.
      Other genes previously identified were only regulated in the duodenum. Overall,
      these studies demonstrate similarities and distinct differences in the genetic
      response to iron deprivation in the duodenum versus jejunum and provide evidence
      that more distal gut segments also may play a role in increasing iron absorption
      in iron-deficiency anemia.

PMID- 16629163
TI  - The functional links between prion protein and copper.
AB  - Prion diseases are fatal neurodegenerative disorders associated with the
      conversion of the cellular prion protein (PrPC) into a pathologic isoform.
      Although the physiological function of PrPC remains unknown, evidence relates
      PrPC to copper metabolism and oxidative stress as suggested by its copper-binding
      properties in the N-terminal octapeptide repeat region. This region also reduces
      copper ions in vitro, and this reduction ability is associated with the
      neuroprotection exerted by the octarepeat region against copper in vivo. In
      addition, the promoter region of the PrPC gene contains putative metal response
      elements suggesting it may be regulated by heavy metals. Here we address some of
      the evidence that support a physiological link between PrPC and copper. Also, in
      vivo experiments suggesting the physiological relevance of PrPC interaction with
      heparan sulfate proteoglycans are discussed.

PMID- 16629164
TI  - Homeostatic and toxic mechanisms regulating manganese uptake, retention, and
      elimination.
AB  - This review attempts to summarize and clarify our basic knowledge as to the
      various factors that potentially influence the risks imposed from chronic
      exposure to high atmospheric levels of manganese (Mn). The studies describe the
      interrelationship of the different systems in the body that regulate Mn
      homeostasis by characterizing specific, biological components involved in its
      systemic and cellular uptake and its elimination from the body. A syndrome known
      as manganism occurs when individuals are exposed chronically to high levels of
      Mn, consisting of reduced response speed, intellectual deficits, mood changes,
      and compulsive behaviors in the initial stages of the disorder to more prominent
      and irreversible extrapyramidal dysfunction resembling Parkinson's disease upon
      protracted exposure. Mn intoxication is most often associated with occupations in
      which abnormally high atmospheric concentrations prevail, such as in welding and
      mining. There are three potentially important routes by which Mn in inspired air
      can gain access the body to: 1) direct uptake into the CNS via uptake into the
      olfactory or trigeminal presynaptic nerve endings located in the nasal mucosa and
      the subsequent retrograde axonal transport directly into the CNS; 2) transport
      across the pulmonary epithelial lining and its subsequent deposition into lymph
      or blood; and/or 3) mucocilliary elevator clearance from the lung and the
      subsequent ingestion of the metal in the gastrointestinal tract. Each of these
      processes and their overall contribution to the uptake of Mn in the body is
      discussed in this review as well as a description of the various mechanisms that
      have been proposed for the transport of Mn across the bloodbrain barrier which
      include both a transferrin-dependent and a transferrin-independent process that
      may involve store-operated Ca channels.

PMID- 16629165
TI  - Translational control of ceruloplasmin gene expression: beyond the IRE.
AB  - Translational control is a common regulatory mechanism for the expression of iron
      related proteins. For example, three enzymes involved in erythrocyte development
      are regulated by three different control mechanisms: globin synthesis is
      modulated by heme-regulated translational inhibitor, erythroid 5-aminolevulinate
      synthase translation is inhibited by binding of the iron regulatory protein to
      the iron response element in the 5'-untranslated region (UTR); and 15
      lipoxygenase is regulated by specific proteins binding to the 3'-UTR.
      Ceruloplasmin (Cp) is a multi-functional, copper protein made primarily by the
      liver and by activated macrophages. Cp has important roles in iron homeostasis
      and in inflammation. Its role in iron metabolism was originally proposed because
      of its ferroxidase activity and because of its ability to stimulate iron loading
      into apo-transferrin and iron efflux from liver. We have shown that Cp mRNA is
      induced by interferon (IFN)-gamma in U937 monocytic cells, but synthesis of Cp
      protein is halted by translational silencing. The silencing mechanism requires
      binding of a cytosolic inhibitor complex, IFN-Gamma-Activated Inhibitor of
      Translation (GAIT), to a specific GAIT element in the Cp 3'-UTR. Here, we
      describe our studies that define and characterize the GAIT element and elucidate
      the specific trans-acting proteins that bind the GAIT element. Our experiments
      describe a new mechanism of translational control of an iron-related protein and
      may shed light on the role that macrophage-derived Cp plays at the intersection
      of iron homeostasis and inflammation.

PMID- 16629166
TI  - Iron homeostasis in the lung.
AB  - Iron is essential for many aspects of cellular function. However, it also can
      generate oxygen-based free radicals that result in injury to biological
      molecules. For this reason, iron acquisition and distribution are tightly
      regulated. Constant exposure to the atmosphere results in significant exposure of
      the lungs to catalytically active iron. The lungs have a mechanism for
      detoxification to prevent associated generation of oxidative stress. Those same
      proteins that participate in iron uptake in the gut are also employed in the
      lung, to transport iron intracellularly and sequester it in an inactive form
      within ferritin. The release of metal is expedited (as transferrin and ferritin)
      from lung tissue to the respiratory lining fluid for clearance by the
      mucocilliary pathway or to the reticuloendothelial system for long-term storage.
      This pathway is likely to be the major method for the control of oxidative stress
      presented to the respiratory tract.

PMID- 16629167
TI  - DMT1: which metals does it transport?
AB  - DMT1-Divalent Metal (Ion) Transporter 1 or SLC11A2/DCT1/Nramp2 - transports Fe2+
      into the duodenum and out of the endosome during the transferrin cycle. DMTI also
      is important in non-transferrin bound iron uptake. It plays similar roles in Mn2+
      trafficking. Voltage clamping showed that six other metals evoked currents, but
      it is unclear if these metals are substrates for DMT1. This report summarizes
      progress on which metals DMT1 transports, focusing on results from the authors'
      labs. We recently cloned 1A/+IRE and 2/-IRE DMT1 isoforms to generate HEK293 cell
      lines that express them in a tetracycline-inducible fashion, then compared
      induced expression to uninduced expression and to endogenous DMT1 expression.
      Induced expression increases approximately 50x over endogenous expression and
      approximately 10x over uninduced levels. Fe2+, Mn2+, Ni2+ and Cu1+ or Cu2+ are
      transported. We also explored competition between metal ions using this system
      because incorporation essentially represents DMT1 transport and find this order
      for transport affinity: Mn>?Cd>?Fe>Pb-Co-Ni>Zn. The effects of decreased DMT1
      also could be examined. The Belgrade rat has diminished DMT1 function and thus
      provides ways of testing. A series of DNA constructs that generate siRNAs
      specific for DMT1 or certain DMT1 isoforms yield another way to test DMT1-based
      transport.

PMID- 16629168
TI  - Cop-like operon: structure and organization in species of the Lactobacillale
      order.
AB  - Copper is an essential and toxic trace metal for bacteria and, therefore, must be
      tightly regulated in the cell. Enterococcus hirae is a broadly studied model for
      copper homeostasis. The intracellular copper levels in E. hirae are regulated by
      the cop operon, which is formed by four genes: copA and copB that encode ATPases
      for influx and efflux of copper, respectively; copZ that encodes a copper
      chaperone; and copY, a copper responsive repressor. Since the complete genome
      sequence for E. hirae is not available, it is possible that other genes may
      encode proteins involved in copper homeostasis. Here, we identified a cop-like
      operon in nine species of Lactobacillale order with a known genome sequence. All
      of them always encoded a CopY-like repressor and a copper ATPase. The alignment
      of the cop-like operon promoter region revealed two CopY binding sites, one of
      which was conserved in all strains, and the second was only present in species of
      Streptococcus genus and L. johnsonii. Additional proteins associated to copper
      metabolism, CutC and Cupredoxin, also were detected. This study allowed for the
      description of the structure and organization of the cop operon and discussion of
      a phylogenetic hypothesis based on the differences observed in this operon's
      organization and its regulation in Lactobacillale order.

PMID- 16629169
TI  - Inhibition of iron and copper uptake by iron, copper and zinc.
AB  - Interactions of micronutrients can affect absorption and bioavailability of other
      nutrients by a number of mechanisms. In aqueous solutions, and at higher uptake
      levels, competition between elements with similar chemical characteristics and
      uptake process can take place. The consequences of these interactions may depend
      on the relative concentrations of the nutrients. In this work, we measure the
      effects of increasing concentrations of iron, zinc, and copper on iron and copper
      uptake in Caco-2 cells. Intracellular Fe or Cu levels were affected by incubating
      with increased concentrations of metals. However, when the cells already had
      different intracellular metal concentration, the uptake of Fe or Cu was nor
      affected. In competition studies, we showed that Cu and Zn inhibited Fe uptake,
      and while Fe inhibited Cu uptake, Zn did not. When the three metals were given
      together (1:1:1 ratio), Fe or Cu uptake was inhibited approximately 40%. These
      results point to a potential risk in the absorption and bioavailability of these
      minerals by the presence of other minerals in the diet. This aspect must be
      considered in food supplementation and fortification programs.

PMID- 16629170
TI  - Antioxidant responses of cortex neurons to iron loading.
AB  - Brain cells have a highly active oxidative metabolism, yet they contain only low
      to moderate superoxide dismutase and catalase activities. Thus, their antioxidant
      defenses rely mainly on cellular reduced glutathione levels. In this work, in
      cortical neurons we characterized viability and changes in reduced and oxidized
      glutathione levels in response to a protocol of iron accumulation. We found that
      massive death occurred after 2 days in culture with 10 microM Fe. Surviving cells
      developed an adaptative response that included increased synthesis of GSH and the
      maintenance of a glutathione-based reduction potential. These results highlight
      the fundamental role of glutathione homeostasis in the antioxidant response and
      provide novel insights into the adaptative mechanisms of neurons subjected to
      progressive iron loads.

PMID- 16629171
TI  - Possible roles of the hereditary hemochromatosis protein, HFE, in regulating
      cellular iron homeostasis.
AB  - Hereditary hemochromatosis (HH) is the most common inherited disorder in people
      of Northern European descent. Over 83% of the cases of HH result from a single
      mutation of a Cys to Tyr in the HH protein. HFE. This mutation causes a recessive
      disease resulting in an accumulation of iron in selected tissues. Iron overload
      damages these organs leading to cirrhosis of the liver, diabetes, cardiomyopathy,
      and arthritis. The mechanism by which HFE influences iron homeostasis in cells
      and in the body remains elusive. Lack of functional HFE in humans produces the
      opposite effects in different cell types in the body. In the early stages of the
      disease. Kupffer cells in the liver and enterocytes in the intestine cells are
      iron depleted and have low intracellular ferritin levels, whereas hepatocytes in
      the liver are iron overloaded and have high intracellular iron levels. This
      review gives the background and a model as to possible mechanisms of how HFE
      could exert different effects on iron homeostasis in different cell types.

PMID- 16629172
TI  - Hereditary hemochromatosis: an opportunity for gene therapy.
AB  - Levels of body iron should be tightly controlled to prevent the formation of
      oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic
      cytokines, which result in damage to a number of organs. Enterocytes in the
      intestinal villae are involved in the apical uptake of iron from the intestinal
      lumen: iron is further exported from the cells into the circulation. The apical
      divalent metal transporter-1 (DMT1) transports ferrous iron from the lumen into
      the cells, while the basolateral transporter ferroportin extrudes iron from the
      enterocytes into the circulation. Patients with hereditary hemochromatosis
      display an accelerated transepithelial uptake of iron, which leads to body iron
      accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis,
      and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is
      the most prevalent genetic disease in Caucasians, with a prevalence of one in 300
      subjects. The majority of patients with hereditary hemochromatosis display
      mutations in the gene coding for HFE, a protein that normally acts as an
      inhibitor of transepithelial iron transport. We discuss the different control
      points in the homeostasis of iron and the different mutations that exist in
      patients with hereditary hemochromatosis. These control sites may be influenced
      by gene therapeutic approaches; one general therapy for hemochromatosis of
      different etiologies is the inhibition of DMT1 synthesis by antisense-generating
      genes, which has been shown to markedly inhibit apical iron uptake by intestinal
      epithelial cells. We further discuss the most promising strategies to develop
      gene vectors and deliver them into enterocytes.

PMID- 16629173
TI  - Gene expression profiling in wild-type and metallothionein mutant fibroblast cell
      lines.
AB  - The role of metallothioneins (MT) in copper homeostasis is of great interest, as
      it appears to be partially responsible for the regulation of intracellular copper
      levels during adaptation to extracellular excess of the metal. To further
      investigate a possible role of MTs in copper metabolism, a genomics approach was
      utilized to evaluate the role of MT on gene expression. Microarray analysis was
      used to examine the effects of copper overload in fibroblast cells from normal
      and MT I and II double knock-out mice (MT-/-). As a first step, we compared genes
      that were significantly upregulated in wild-type and MT-/- cells exposed to
      copper. Even though wild-type and mutant cells are undistinguishable in terms of
      their morphological features and rates of growth, our results show that MT-/-
      cells do not respond with induction of typical markers of cellular stress under
      copper excess conditions, as observed in the wild-type cell line, suggesting that
      the transcription initiation rate or the mRNA stability of stress genes is
      affected when there is an alteration in the copper store capacity. The functional
      classification of other up-regulated genes in both cell lines indicates that a
      large proportion (>80%) belong to two major categories: 1) metabolism; and 2)
      cellular physiological processes, suggesting that at the transcriptional level
      copper overload induces the expression of genes associated with diverse molecular
      functions. These results open the possibility to understand how copper
      homeostasis is being coordinated with other metabolic pathways.

PMID- 16629174
TI  - Vesicular transport of fe and interaction with other metal ions in polarized
      Caco2 cell monolayers.
AB  - Two aspects of the mechanisms by which iron is absorbed by the intestine were
      studied in the Caco2 cell model, using 59Fe(II)-ascorbate. Data showing the
      importance of vesicular processes and cycling of apotransferrin (apoTf) to uptake
      and overall transport of Caco2 cell monolayers (or basolateral 59Fe release) were
      obtained by comparing effects of: a) adding apoTf to the basal chamber; b) adding
      vesicular transport inhibitors; or c) cooling to 4 degrees C. These showed that
      apoTf may be involved in as much as half of Fe transfer across the basolateral
      membrane, and that vesicular processes may also play a role in non-apoTf
      dependent Fe transport. Studies were initiated to examine potential interactions
      of other metal ions with Fe(II) via DMT1. Kinetic data showed a single, saturable
      process for uptake of Fe(II) that was pH dependent and had a Km of 7 microM. An
      excess of Mn(II) and Cu(I) over Fe(II) of 200: 1 (microM: microM) in 1 mM
      ascorbate markedly inhibited Fe uptake. The kinetics were not competitive. Km
      increased and Vmax decreased. We conclude that vesicular transport, involving
      endo- and exocytosis at both ends of the enterocyte, is a fundamental aspect of
      intestinal iron absorption and that DMT1 may function as a transporter not just
      for divalent but also for monovalent metal ions.

PMID- 16629175
TI  - Iron and glutathione at the crossroad of redox metabolism in neurons.
AB  - Neurons, as non-dividing cells, encounter a myriad of stressful conditions
      throughout their lifespan. In particular, there is increasing evidence that iron
      progressively accumulates in the brain with age and that iron induced oxidative
      stress is the cause of several forms of neurodegeneration. Here, we review recent
      evidence that gives support to the following notions: 1) neuronal iron
      accumulation leads to oxidative stress and cell death; 2) neuronal survival to
      iron accumulation associates with decreased expression of the iron import
      transporter DMT1 and increased expression of the efflux transporter IREG1; and 3)
      the adaptive process of neurons towards iron-induced oxidative stress includes a
      marked increase in both the expression of the catalytic subunit of gamma
      glutamate-cysteine ligase and glutathione. These findings may help to understand
      aging-related neurodegeneration hallmarks: oxidative damage, functional
      impairment and cell death.

PMID- 16629176
TI  - Iron at the center of ferritin, metal/oxygen homeostasis and novel dietary
      strategies.
AB  - Bioiron - central to respiration, photosynthesis and DNA synthesis and
      complicated by radical chemistry with oxygen - depends on ferritin, the super
      family of protein nanocages (maxi-ferritins in humans, animals, plant, and
      bacteria, and mini-ferritins, also called DPS proteins, in bacteria) for iron and
      oxygen control. Regulation of ferritin synthesis, best studied in animals, uses
      DNA transcription and mRNA translation check points. Ferritin is a member of both
      the "oxidant stress response" gene family that includes thioredoxin reductase and
      quinine reductase, and a member of the iron responsive gene family that includes
      ferroportin and mt-aconitase ferritin DNA regulation responds preferentially to
      oxidant response inducers and ferritin mRNA to iron inducers: heme confers
      regulator synergy. Ferritin proteins manage iron and oxygen, with ferroxidase
      sites and iron + oxygen substrates to form mineral of both Fe and O atoms; maxi
      ferritins contribute more to cellular iron metabolism and mini-ferritins to
      stress responses. Iron recovery from ferritin is controlled by gated protein
      pores, possibly contributing to iron absorption from ferritin, a significant
      dietary iron source. Ferritin gene regulation is a model for integrating DNA/mRNA
      controls, while ferritin protein function is central to molecular nutrition
      cellular metabolism at the crossroads of iron and oxygen in biology.

PMID- 16629177
TI  - Divalent cations as modulators of neuronal excitability: emphasis on copper and
      zinc.
AB  - Based on indirect evidence, a role for synaptically released copper and zinc as
      modulators of neuronal activity has been proposed. To test this proposal
      directly, we studied the effect of copper, zinc, and other divalent cations on
      voltage-dependent currents in dissociated toad olfactory neurons and on their
      firing rate induced by small depolarizing currents. Divalent cations in the
      nanomolar range sped up the activation kinetics and increased the amplitude of
      the inward sodium current. In the micromolar range, they caused a dose dependent
      inhibition of the inward Na+ and Ca2+ currents (INa and ICa) and reduced de
      amplitude of the Ca2+-dependent K+ outward current (ICa-K). On the other hand,
      the firing rate of olfactory neurons increased when exposed to nanomolar
      concentration of divalent cations and decreased when exposed to micromolar
      concentrations. This biphasic effect of divalent cations on neuronal excitability
      may be explained by the interaction of these ions with high and low affinity
      sites in voltage-gated channels. Our results support the idea that these ions are
      normal modulators of neuronal excitability.

PMID- 16629178
TI  - Understanding copper homeostasis in humans and copper effects on health.

PMID- 16629179
TI  - Effect of iron on the activation of the MAPK/ERK pathway in PC12 neuroblastoma
      cells.
AB  - Recent evidence suggests that reactive oxygen species function as second
      messenger molecules in normal physiological processes. For example, activation of
      N-Methyl-D-Aspartate receptor results in the production of ROS, which appears to
      be critical for synaptic plasticity, one of the cellular mechanisms that underlie
      learning and memory. In this work, we studied the effect of iron in the
      activation of MAPK/ERK pathway and on Ca2+ signaling in neuronal PC12 cells. We
      found that iron-dependent generation of hydroxyl radicals is likely to modulate
      Ca2+ signaling through RyR calcium channel activation, which, in turn, activates
      the MAPK/ERK pathway. These findings underline the relevance of iron in normal
      neuronal function.

PMID- 16629180
TI  - Regulation of transepithelial transport of iron by hepcidin.
AB  - Hepcidin (Hepc) is a 25 amino acid cationic peptide with broad antibacterial and
      antifungal actions. A likely role for Hepc in iron metabolism was suggested by
      the observation that mice having disruption of the gene encoding the
      transcription factor USF2 failed to produce Hepc mRNA and developed spontaneous
      visceral iron overload. Lately, Hepc has been considered the "stores regulator,"
      a putative factor that signals the iron content of the body to intestinal cells.
      In this work, we characterized the effect of Hepc produced by hepatoma cells on
      iron absorption by intestinal cells. To that end, human Hepc cDNA was cloned and
      overexpressed in HepG2 cells and conditioned media from Hepc-overexpressing cells
      was used to study the effects of Hepe on intestinal Caco-2 cells grown in
      bicameral inserts. The results indicate that Hepc released by HepG2 inhibited
      apical iron uptake by Caco-2 cells, probably by inhibiting the expression of the
      apical transporter DMT1. These results support a model in which Hepc released by
      the liver negatively regulates the expression of transporter DMT1 in the
      enterocyte.

PMID- 16629181
TI  - Heme oxygenase 1 overexpression increases iron fluxes in caco-2 cells.
AB  - Heme oxygenase-1 is a microsomal enzyme that, when induced by stress, protects
      the cells from oxidative injury. Heme oxygenase-1 participates in the cleavage of
      the heme ring producing biliverdin, CO and ferrous Fe. The released Fe becomes
      part of intracellular Fe pool and can be stored in ferritin or released by an
      iron exporter. The mechanism by which heme enters cells is not completely
      understood, although it had been suggested that it might be internalized by an
      endocytosis process. In this study, we expressed a full-length Heme oxygenase-1
      cDNA in Caco-2 cells and measured intracellular iron content, heme-iron uptake
      and transport and immunolocalization of heme oxygenase-1 in these cells. We found
      that heme oxygenasc-1 expressing cells showed increased apical heme iron uptake
      and transepithelial transport when compared to control cells. These results
      suggested that heme oxygenase-1 mediates heme iron influx and efflux in
      intestinal cells.

PMID- 16629182
TI  - Characterization of mitochondrial iron uptake in HepG2 cells.
AB  - There is increasing evidence that accumulation of redox-active iron in
      mitochondria leads to oxidative damage and contributes to various
      neurodegenerative diseases, such as Friedreich's ataxia and Parkinsons disease.
      In this work, we examined the existence of regulatory mechanisms for
      mitochondrial iron uptake and storage. To that end, we used rhodamine B-[(1,10
      phenanthrolin-5-yl)amino carbonyl] benzyl ester, a new fluorescent iron-sensitive
      probe that is targeted specifically to the mitochondrion. We found that
      extracellular iron was incorporated readily into mitochondria in an apparently
      saturable process. Moreover, the rate of iron incorporation responded to the Fe
      status of the cell, an indication that the mitochondrion actively regulates its
      iron content.

PMID- 16629183
TI  - Satisfaction survey.

PMID- 16629184
TI  - Urban Animal Management Committee.

PMID- 16629185
TI  - Live export--a critical time.

PMID- 16629186
TI  - Veterinary public health program.

PMID- 16629187
TI  - AMRRIC and the DogPeople conference.

PMID- 16629188
TI  - Populate and perish.

PMID- 16629189
TI  - Molecular subtyping of feline immunodeficiency virus from domestic cats in
      Australia.
AB  - OBJECTIVE: To determine the prevalent subtypes of feline immunodeficiency virus
      (FIV) present in the domestic cat population of Australia. METHOD: Blood samples
      were collected from 41 FIV antibody positive cats from four cities across
      Australia. Following DNA extraction, polymerase chain reaction (PCR) was
      performed to amplify the variable V3-V5 region of the envelope (env) gene.
      Genotypes were assessed by direct sequencing of PCR products and comparison with
      previously reported FIV sequences. Phylogenetic analysis allowed classification
      of the Australian sequences into the appropriate subtype. RESULTS: Of the 41 FIV
      samples, 40 were found to cluster with previously reported subtype A isolates,
      whilst the remaining sample grouped within subtype B. CONCLUSIONS: Subtype A was
      found to be the predominant FIV subtype present in Australia, although subtype B
      was also found. These results broaden our knowledge of the genetic diversity of
      FIV and the associated implications for preventative, diagnostic and therapeutic
      approaches.

PMID- 16629190
TI  - Surgical correction of ventricular septal defect with aortic regurgitation in a
      dog.
AB  - An 8-month-old entire Miniature Dachshund, weighing 4.2 kg, was presented for
      examination following delvelopment of a cough. Ventricular septal defect had been
      diagnosed tentatively in its infancy on the basis of a cardiac murmur detected by
      auscultation and echocardiography. Echocardiography using a B mode right
      parasternal long-axis view showed a defect at the atrioventricular junction and a
      thickened cusp of the aortic valve prolapsing into the defect. Colour-flow
      Doppler showed shunt blood flow across the defect at the level of the
      atrioventricular junction, from left to right. The sinus of Valsalva was dilated,
      with turbulent blood flow. Aortic regurgitation was also observed. Cardiac
      catheterisation studies confirmed the diagnosis of a supracristal ventricular
      septal defect with aortic regurgitation. Despite medication with digoxin,
      enalapril and aminophylin, started from the first admission, left ventricular
      internal dimensions gradually increased, and fractional shortening of the left
      ventricle gradually decreased. Surgery, with the aid of extracorporeal
      circulation, to close the ventricular septal defect, was performed 1 year after
      the initial examination. The aortic valve was left untreated. Postoperatively,
      the systolic murmur disappeared. Shunt flow from the left to the right ventricle
      was no longer observed on echocardiography, however there was still a small
      amount of aortic regurgitation during diastole visualised with colour-flow
      Doppler echocardiography. The prolapse of the cusp of the aortic valve on B-mode
      echocardiography was no longer observed and thickening of the cusp had not
      progressed. Left ventricular function measurement using M mode echocardiography
      showed a reduced left ventricular volume overload with reduced left ventricular
      internal dimensions and increased fractional shortening. The cough was relieved
      and no follow-up medication was scheduled. Early surgical closure of the
      ventricular septal defect improved the patient's condition and controlled
      prolapse and thickening of the aortic valve.

PMID- 16629191
TI  - Inheritance of proportionate dwarfism in Angus cattle.
AB  - OBJECTIVE: To determine the mode of inheritance of congenital proportionate
      dwarfism in Angus and Angus crossbred cattle, initially detected in two
      commercial beef herds in northern New South Wales. DESIGN: Matings of normal
      carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his
      unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected
      daughters of the carrier sires. PROCEDURE: Two carrier Angus bulls and nine
      unaffected daughters, all of whom were completely indistinguishable from normal
      animals, were purchased for controlled breeding studies under known nutritional
      and disease conditions. Affected and carrier individuals were examined for the
      presence of obvious chromosomal abnormalities. RESULTS: Angus dwarfism has been
      successfully reproduced under controlled experimental conditions over successive
      years using unrelated dams and is undoubtedly heritable. The high frequency of
      occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of
      matings of the Angus sires to unrelated females of diverse breeding is not
      compatible with recessive inheritance, because of the negligible frequency of
      proportionate dwarfism in the breeds of the dams. Both paternal and maternal
      transmission of the defect was demonstrated, so that imprinting in the strict
      sense of a gene that is only expressed when received from the male parent appears
      not to be involved. Tested individuals showed no evidence of gross chromosomal
      abnormality. Dominant autosomal inheritance with incomplete penetrance was
      indicated by the lack of expression of the defective gene in the two Angus sires
      and in three unaffected daughters who produced dwarf calves from matings to the
      Piedmontese bull. CONCLUSIONS: The mode of inheritance is that of a single
      autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated
      from the observed incidence of 23/61 affected offspring of the two carrier Angus
      bulls mated to unrelated dams. Simple genetic models involving either (i) an
      unstable mutant which changes at high frequency to the expressed dominant
      dwarfing allele during gametogenesis, or (ii) a dominant allele with penetrance
      determined by an unlinked modifying locus, are shown to be compatible with the
      experimental data. Both models indicate that penetrance of the dwarfing gene may
      possibly be higher in matings involving carrier daughters of the two Angus bulls.

PMID- 16629192
TI  - The occurrence of congenital heart defects in an inbred herd of pigs in
      Australia.
AB  - OBJECTIVE: To report on the first case of congenital heart defects in pigs in
      Australia. DESIGN: Retrospective analysis of case records from an inbred herd of
      "Westran" pigs at the University of Sydney, between January 2001 and December
      2004. Detailed gross and histological examination of 15 hearts from pigs that had
      died or were euthanased in 2004. CASE DETAILS: The necropsy records from a
      population of 471 pigs that had died (106 pigs) or were euthanased for research
      purposes (365 pigs) were analysed and the incidence of heart defects recorded,
      together with basic demographic data. No attempts were made to diagnose the
      condition in live pigs. RESULTS: Congenital heart defects were diagnosed in 6.4%
      of pigs but this is likely to be an underestimate of the incidence of the
      deformity. Eighteen pigs died on the farm as a result of the defect, and 12 pigs
      were diagnosed with the defect as an incidental finding. The most common
      abnormality seen at necropsy was a sac-like dilatation on the right lateral
      surface of the right atrium. This was associated with secondary deformity and
      hypoplasia of the adjacent left ventricle, interventricular region and part of
      the right ventricle. All hearts showed atrial septal defects of varying size.
      CONCLUSION: This is the first reported case of congenital heart defects in pigs
      in Australia, and one of less than five reported cases of atrial septal defects
      in pigs in the world. The authors conclude that there may be an element of
      genetic predisposition to the malformation, since it has only been reported in
      this inbred line of pigs.

PMID- 16629193
TI  - Probable Malva parviflora (small flowered mallow) intoxication in sheep in
      Western Australia.

PMID- 16629194
TI  - Unilateral ataxia and head tilt in a 7-year-old Thoroughbred stallion.
      Temporohyoid osteoarthropathy.

PMID- 16629195
TI  - Pleuropneumonia as a sequela of myelography and general anaesthesia in a
      Thoroughbred colt.
AB  - A 3-year-old Thoroughbred colt was presented to the University Veterinary Centre
      Camden for evaluation of ataxia. The horse was anaesthetised to facilitate
      cervical radiography and myelographic examination of the spinal cord. Recovery
      from anaesthesia was uneventful. Five days after general anaesthesia the horse re
      presented with pleuropneumonia. It was euthanased 24 hours after presentation on
      humane grounds. Necropsy revealed severe tracheal erosion over the middle third
      of the ventral surface of the trachea, pleuropneumonia and narrowing of the
      cervical cord between C4 and C6. It is postulated that extension and flexion of
      the neck during myelography resulted in movement of the endotracheal tube cuff,
      causing the tracheal lesion and predisposing the colt to pleuropneumonia. Severe
      tracheal lesions and pleuropneumonia have not been reported as sequela of equine
      myelography, and should be considered as possible complications following
      repeated cervical manipulation during myelography in the horse.

PMID- 16629196
TI  - Effects of temperature and duration of sample storage on the haematological
      characteristics of western grey kangaroos (Macropus fuliginosus).
AB  - OBJECTIVE: To investigate the effects of storage duration and temperature on
      haematological analyses performed on blood from the western grey kangaroo
      (Macropus fuliginosis). METHOD: Blood samples from five western grey kangaroos
      were stored at 4 degrees C, 24 degrees C and 36 degrees C. Each sample was
      analysed haematologically over a 5-day period. RESULTS: The blood samples
      maintained optimal stability at 4 degrees C. At this temperature the
      haematological values remained essentially unchanged for the duration of the
      study, while samples stored at 36 degrees C and 24 degrees C showed significant
      changes in some haematological measures by 12 h and 48 h, respectively.
      Disturbances in leukocyte morphology were evident, to varying degrees, in all
      samples. CONCLUSIONS: Blood samples from macropodids should be tested within 48 h
      of collection if stored at a room temperature of about 24 degrees C. Where
      testing is to be delayed for more than 48 h, samples should be refrigerated as
      soon as possible. Exposure of samples to heat in excess of 24 degrees C should be
      avoided at all times.

PMID- 16629198
TI  - Improving health services.

PMID- 16629197
TI  - Standing together.

PMID- 16629199
TI  - Spread too thin.

PMID- 16629200
TI  - We all love what we do.

PMID- 16629201
TI  - Call to action on indigenous health.

PMID- 16629202
TI  - Nurses take a stand against inequality.

PMID- 16629203
TI  - Support for nurses a welcome first.

PMID- 16629204
TI  - Surgery to combat obesity still not a health funding priority.

PMID- 16629205
TI  - Supporting women at work.

PMID- 16629206
TI  - Violence against nurses--looking forward to a safer future.

PMID- 16629207
TI  - Take a look at a bleak future under the Howard government's IR changes.

PMID- 16629208
TI  - Capturing the image of nursing.

PMID- 16629209
TI  - Putting 'U' back into QUM.

PMID- 16629210
TI  - Taking it to the streets.

PMID- 16629211
TI  - Putting the 'care' back into aged care.
AB  - Aged care is well and truly back on the political agenda in Australia. While the
      mainstream media has recently exposed a number of horrific cases of alleged abuse
      in aged care facilities it has done little to highlight the failings of social
      policy over time or to foster debate on how to improve the care of older
      Australians. What are the barriers to providing safe and quality aged care to a
      growing number of our citizens and how do we overcome them? If you relied on the
      recent media coverage for your impression of aged care you could be forgiven for
      thinking it is all bad news. But there are facilities providing high quality care
      and stories of nurses working wonders in the face of adversity. Cathy Beadnell
      considers some of the broader cultural and workforce issues in aged care.

PMID- 16629212
TI  - Evidence for intravenous antibiotic therapy in the community.

PMID- 16629213
TI  - A day in the life.

PMID- 16629214
TI  - Transplant assistance for type 1 diabetes.

PMID- 16629215
TI  - 'Seaweed' human islet clinical trials underway.

PMID- 16629216
TI  - Transplant diary.

PMID- 16629217
TI  - A family's perspective on organ donation.

PMID- 16629218
TI  - The gift of a second chance.

PMID- 16629219
TI  - Nursing challenges associated with non heart beating organ donation.

PMID- 16629220
TI  - A little respect goes a long way.

PMID- 16629221
TI  - Renal osteodystrophy: what's in a name? Presentation of a clinically useful new
      model to interpret bone histologic findings.
AB  - Renal osteodystrophy begins early in the course of chronic kidney disease and
      occurs almost without exception in all patients with Stage 5 disease (CKD-5).
      Bone biopsies and evaluation of mineralized bone sections after double
      tetracycline-labeling are currently considered the gold standard for diagnosis
      and classification of renal osteodystrophy. Nevertheless, bone biopsies are
      rarely employed. This is, at least in part, related to the paucity of
      nephrologists trained in performance of the procedure and the fact that reports
      of the histologic results are not easily translatable to clinical practice.
      Results are usually given qualitatively, using non-uniform classifications or by
      histomorphometric evaluations which are esoteric to most nephrologists. We
      suggest here that histomorphometric evaluation can be reserved for research and
      special situations. Also, the customarily used qualitative classification should
      be replaced by a clinically useful nomenclature, provided the interpretation is
      done by an individual with sufficient experience in bone pathology. We present a
      new interactive nomenclature for renal osteodystrophy that addresses
      abnormalities of turnover, abnormalities of bone balance, and abnormalities of
      mineralization. The new nomenclature, thus, includes disorders of high- and low
      turnover with consideration of the interrelation with positive or negative bone
      balance with or without mineralization defect. In this schema, changes in bone
      status are described as deviations from a norm, and treatment is geared toward
      normalizing values rather than creating any absolute change in one direction or
      another. It is hoped that such a classification will be easily usable, clinically
      more relevant, and more amenable to individualized treatment guidance.

PMID- 16629222
TI  - Clinical pathological correlates of renal biopsy in elderly patients.
AB  - BACKGROUND: Reports have shown that well-defined histological patterns do not
      always correspond to equally clear clinical pictures, particularly so in elderly
      patients. METHODS: With the aim of assessing clinicopathological correlations in
      the population aged >65 years with that of lower age, we retrospectively analyzed
      computerized records of renal needle biopsies consecutively performed in the
      decade 1991-2000 in our unit. RESULTS: Among the 392 eligible subjects, there
      were 150 patients 65 years of age and more, 76 of whom were over 70. The average
      serum creatinine was 2.9 mg/dl, with values > 3.5 mg/dl in 25% of cases. The
      major indication to biopsy was nephrotic syndrome followed by chronic renal
      failure both in the young adult and the elderly population. The rapidly
      progressive form led more often to renal biopsy in the elderly patients, and the
      different prevalence was statistically significant (p < 0.05), as was the higher
      prevalence of urinary anomalies in the young-adult population. Regarding renal
      histology, the crescentic necrotizing forms were significantly more frequent in
      the elderly patients, while IgAN, minimal change disease and SLE predominate in
      young adults. The most relevant result is the greater prevalence of crescentic
      necrotizing glomerulonephritis in elderly patients, not only in the cases
      presenting clinically as rapidly progressive renal failure and acute renal
      failure, but also in those with the clinical picture of chronic renal failure.
      CONCLUSIONS: Re-evaluation of our case files verifies the importance of the
      bioptic approach in selected cases with stages 3-4 chronic kidney damage. This
      holds true especially for elderly patients.

PMID- 16629223
TI  - Acute and concomitant deterioration of hyponatremia and renal dysfunction
      associated with heart and liver failure.
AB  - BACKGROUND: Although hyponatremia with concomitant renal dysfunction has been
      described anecdotally, little is known about how these two conditions are
      related, which type of renal dysfunction usually occurs, and which patients are
      at risk. METHODS: From 3029 measured serum sodium (S(Na)) concentrations in 3
      months, patients with at least one S(Na) < or =125 mmol/l were selected, and
      divided in patients with at least 1 S(Creat) > or =125 micromol/l (study group,
      n=20), and patients whose S(Creat) remained normal (control group, n=50).
      RESULTS: During the first 5 days of hospitalization, S(Creat) almost doubled in
      the study group from 125 +/- 40 micromol/l to 207 +/- 72 micromol/l, while S(Na)
      decreased concurrently from 130 +/- 2 mmol/l to 122 +/- 3 mmol/l. The peak
      S(Creat) and S(Na) values coincided, and the average courses were highly
      correlated (r = 0.88, p < 0.001). The study group more often had heart failure
      (10/20 vs. 1/50, p < 0.001) and liver failure (7/20 vs. 4/50, p = 0.009), and
      received more often loop diuretics (13/20 vs. 12/50, p = 0.002), spironolactone
      (11/20 vs. 7/50, p = 0.001), and/or angiotensin-converting enzyme inhibitors
      (5/20 vs. 2/50, p = 0.02). Four patients were admitted to the intensive care (10
      in control group, p = 1.0), and 5 patients died (10 in control group, p = 0.7).
      CONCLUSIONS: Renal dysfunction is common in severe hyponatremia and usually
      develops in an acute-on-chronic fashion with concomitant deterioration of both
      conditions. This concourse is associated with heart failure, liver failure,
      and/or a renal drug regimen. Given the recent results of clinical trials, this
      patient group may be especially suitable for treatment with vasopressin
      antagonists.

PMID- 16629224
TI  - The prevalence and risk factors of microalbuminuria in normoglycemic,
      normotensive adults.
AB  - AIMS: Microalbuminuria is a risk factor for renal and cardiovascular disease.
      Recent studies have established this important relationship in patients with
      diabetes or hypertension, yet few studies have shown this relationship in healthy
      subjects. The purpose of this study is to examine the prevalence and the risk
      factors of microalbuminuria in normoglycemic, normotensive adults. SUBJECTS AND
      METHODS: We examined the prevalence of microalbuminuria in the adults who
      voluntarily took part in a health examination program. As a cross-sectional
      study, we examined the risk factors of microalbuminuria in 4883 normoglycemic,
      normotensive healthy adults. RESULTS: The prevalence of microalbuminuria was 2.8%
      in the normoglycemic, normotensive group (n=4883), 10.1% in the hypertensive
      group (n=1250), 16.0% in the diabetes group (n=455) and 5.4% in the total
      subjects (n=6588). The systolic blood pressure, high sensitive C-reactive protein
      (hsCRP) and insulin resistance were independently related with microalbuminuria
      on the logistic regression analysis. The odds ratio of microalbuminuria were 1.04
      (1.02 - 1.05, 95% CI), 1.29 (1.10 - 1.51, 95% CI), and 1.83 (1.15 - 2.92, 95%
      CI), respectively. CONCLUSIONS: These finding suggest that the systolic blood
      pressure, hsCRP and insulin resistance are the independent risk factors for
      microalbuminuria in normoglycemic, normotensive adults.

PMID- 16629225
TI  - Functional characterization of SLC7A9 polymorphisms assumed to influence the
      cystinuria phenotype.
AB  - Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport
      across the luminal membrane of renal tubules and intestine, resulting in
      recurrent nephrolithiasis. While mutations in the SLC3-A1 gene cause type I
      cystinuria, patients with non-type I cystinuria mostly carry mutations in the
      SLC7A9 gene. However, there is evidence that further genetic factors cause and
      influence the cystinuria phenotype. We recently demonstrated that specific
      polymorphisms in Exons 3, 4, 5 and 6 of the SLC7A9 gene show a significant
      different allelic distribution between cystinuria patients and controls. To
      determine the role of the variants in these exons we transfected COS7 cells with
      expression constructs containing different haplotypes. Sequencing of cDNAs
      derived from the resulting SLC7A9 mRNAs did not reveal any differences in
      expression between the minigenes of the specific haplotypes. Our findings suggest
      that the variants in SLC7A9 do not influence splicing behavior. Thus, the reasons
      for the different allelic distribution between cystinuria patients and controls
      remain unclear. It is conceivable that this distribution is caused by the
      association of certain alleles with so far undetected mutations in the gene.

PMID- 16629226
TI  - The isoflavone genistein inhibits LPS-stimulated TNFalpha, but not IL-6
      expression in monocytes from hemodialysis patients and healthy subjects.
AB  - BACKGROUND: Whole blood and peripheral blood mononuclear cells from hemodialysis
      (HD) patients show increased production and secretion of inflammatory cytokines.
      We determined the contribution of blood monocytes to the production of
      inflammatory cytokines in whole blood from HD patients. METHODS: Whole blood and
      isolated mononuclear cells from HD patients and healthy control subjects were
      preincubated with the isoflavone genistein and stimulated with LPS. TNFalpha, IL
      6 and IL-10 formation in the whole blood was measured with ELISA and
      intracellular cytokine formation in CD 14-positive monocytes was determined by
      flow cytometry. RESULTS: Unstimulated blood levels of TNFalpha, IL-6 and IL-10
      were significantly elevated in HD patients compared to controls, but
      intracellular monocyte content of these cytokines was identical between groups.
      LPS induced a robust TNFalpha response in both whole blood and monocytes, and
      TNFalpha formation was 2.3-fold higher in blood from HD patients compared to
      controls. A similar trend was observed in monocytes. Conversely, LPS stimulation
      increased IL-6 levels >1000-fold in whole blood, albeit without a noticeable
      difference between groups. Only minor increases in monocyte IL-6 content were
      observed. The isoflavone genistein did not inhibit IL-6 formation and did not
      alter basal TNFalpha levels, but genistein selectively blocked LPS-induced
      TNFalpha formation in whole blood and monocytes from both groups. CONCLUSION:
      Intracellular levels of TNFalpha, IL-6 and IL-10 in monocytes are
      indistinguishable between HD patients and healthy controls. However, monocytes
      from HD patients are selectively primed for enhanced TNFalpha secretion in
      response to LPS. The selective inhibition of monocyte TNFalpha production by
      genistein may explain the anti-inflammatory action of this phytochemical observed
      in vivo.

PMID- 16629227
TI  - Good response of membranous lupus nephritis to tacrolimus.
AB  - A 22-year-old woman hospitalized for polyarthralgia was diagnosed with systemic
      lupus erythematosus (SLE). She was treated with prednisolone, and her clinical
      manifestations improved. However, she was re-admitted for renal biopsy because of
      persistent hypocomplementemia and development of proteinuria. The biopsy revealed
      segmental spike formation of basement membrane and subepithelial immune complex
      deposition, and membranous lupus nephritis (class V) was diagnosed. When
      tacrolimus was added to prednisolone, the serum complement titer quickly improved
      and proteinuria disappeared after about 11 months. Nevertheless, when tacrolimus
      was replaced examination showed cyclosporine due to gastrointestinal symptoms,
      she complained about arthralgia. Examination showed drop in the serum complement
      titer and recurrence of proteinuria. Renal biopsy at the time of recurrence
      showed increased subepithelial immune complex deposition in the capillary loops
      as compared to the first biopsy, a high degree of thickening of the basement
      membrane, and segmental circumferential interposition in some of the glomeruli.
      Membranous lupus nephritis (classes V + III) was diagnosed. By changing to
      tacrolimus and higher doses of steroids, the serum complement titer improved and
      proteinuria disappeared. This case indicates that tacrolimus can be an effective
      therapeutic agent for membranous lupus nephritis.

PMID- 16629228
TI  - The "nutcracker phenomenon" with orthostatic proteinuria: case reports.
AB  - The nutcracker phenomenon refers to compression of the left renal vein between
      the aorta and the superior mesenteric artery. Clinical features are hematuria,
      abdominal pain, left flank pain, pelvic or scrotal discomfort due to varicocele
      or ovarian vein syndrome. In this report, 2 patients with orthostatic
      proteinuria, in whom nutcracker phenomenon was detected as a cause, are
      presented. One of them had posterior nutcracker with also asymptomatic varicocele
      that was detected during ultrasonographic examination. Nutcracker phenomenon is a
      rare but important clinical condition that should be considered in the
      differential diagnosis of patients with proteinuria and hematuria.

PMID- 16629229
TI  - Crescentic glomerulonephritis associated with rifampicin in a patient co-infected
      with tuberculosis and human immunodeficiency virus.
AB  - A 73-year-old man presented with acute renal failure after 3-month standard
      antituberculosis therapy with rifampicin for pulmonary tuberculosis. Previously
      undiagnosed human immunodeficiency virus (HIV) infection was found at the same
      time. A kidney biopsy showed crescentic glomerulonephritis and tubulointerstitial
      nephritis. Furthermore, endothelial tubuloreticular inclusions were seen on
      electron microscopy. Rifampicin was stopped because it was considered as the most
      possible cause responsible for the rapidly progressive glomerulonephritis (RPGN).
      Immunosuppressive therapy was not carried out because of the risk of aggravation
      of underlying infectious diseases including tuberculosis and HIV. Fortunately,
      renal function recovered 1 month after discontinuation of rifampicin. This case
      presented a clinical challenge in the differential diagnosis of the cause for
      RPGN in such a complex condition and the therapeutic dilemma regarding the use of
      immunosuppressive drugs.

PMID- 16629230
TI  - A case of refractory uremic pleuropericarditis--successful corticosteroid
      treatment.
AB  - We report the case of a patient with uremic pleuropericarditis who showed a
      marked improvement following corticosteroid therapy. A 66-year-old man who had
      been on hemodialysis therapy for 13 years was admitted to our hospital presenting
      with increases in bilateral pleural effusions and pericardial effusion. Repeated
      thoracentesis showed hemorrhagic and exudative findings. Pleural and pericardial
      fluid cytologic examination, bacterial culture and acid-fast staining showed
      negative findings. Despite the administration of antibiotics and antituberculosis
      drugs, low-grade fever continued and C-reactive protein level remained high. A
      pleural biopsy revealed fibrinous pleuritis without infectious disease or
      malignancy. He was diagnosed as having uremic pleuropericarditis on the basis of
      the clinicopathological features, but had been unresponsive to conventional
      treatments including repeated thoracentesis and the continuance of
      hemodiafiltration using nafamostat mesylate. Ultimately, both pleural and
      pericardial effusions were controlled after the treatment with prednisolone at an
      initial dose of 50 mg per day. In conclusion, corticosteroid therapy seems to be
      useful for treating patients with conventional therapy-resistant uremic
      pleuropericarditis.

PMID- 16629231
TI  - Successful maintenance of continuous ambulatory peritoneal dialysis in a patient
      after fungal peritonitis and dialysate leakage.
AB  - Fungal peritonitis (FP) and dialysate leakage have often been reported in
      association with continuous ambulatory peritoneal dialysis (CAPD), which has to
      be discontinued in many cases due to these complications. This report describes
      the first case of dialysate leakage into the urinary bladder of a 70-year-old
      male patient, after the area of the left ureteral ostium had been very deeply
      resected. The leakage probably led to severe fungal peritonitis developing 1 day
      after the ostium resection. The ostium resection was performed in November 2003
      after detection of a carcinoma in situ (Cis) in this area and after previous
      bilateral nephroureterectomies due to multifocal urothelial carcinoma in the
      kidneys, ureters and bladder. In spite of prior fungal peritonitis and dialysate
      leakage, CAPD could be successfully initiated 41 days after biochemical
      manifestation of peritonitis and could be maintained in the patient because of
      the following reasons: early and effective treatment of FP with fluconazole and
      voriconazole, spontaneous occlusion of the slitted ostium area, allowance of
      enough healing time after 2 major abdominal surgeries, during which the patient
      was placed on extracorporal hemodialysis (which had been started 1 day after
      nephroureterectomy and ended after the antimycotic treatment) and thorough
      monitoring of the patient after starting CAPD. In January 2004, the patient could
      be placed on a cycler peritoneal dialysis and was fully rehabilitated 1 year
      later.

PMID- 16629232
TI  - Tuberculous spondylitis in patients with end-stage renal disease undergoing
      chronic hemodialysis therapy.
AB  - Tuberculosis of the spine is not rare in immunocompromised patients and
      particularly in those with end-stage renal disease (ESRD). Furthermore, the
      possible vascular compromise of the spinal cord in patients with diabetic
      nephropathy may result in symptoms of neurological involvement that could lead to
      deterioration and paralysis. We report a series of 4 patients with ESRD
      undergoing dialysis that developed tuberculous spondylitis of the thoracic spine.
      Diabetic nephropathy was the primary cause for chronic kidney disease in 2
      patients; 3 of these patients were treated conservatively with anti-tuberculous
      medication and orthotic splints and were cured. The fourth patient with diabetes
      mellitus and clinically evident signs and symptoms of severe vascular
      insufficiency has additionally developed incomplete paraplegia. A complete
      sensory recovery and partial recovery of the hip flexors and abductors within 3
      months occurred, following decompression of the spine and drainage of the
      abscess, in combination with long-term anti-tuberculous treatment and spinal
      orthosis.

PMID- 16629233
TI  - Bilateral renal enlargement: an unusual presentation of bacterial pyelonephritis.

PMID- 16629234
TI  - Prominent hypophosphatemia due to proximal tubulopathy mimicking Fanconi's
      syndrome in a patient with obstructive jaundice.

PMID- 16629235
TI  - OSMA Centennial: honoring our past, anticipating our future.

PMID- 16629236
TI  - Tobacco-free campus initiative.
AB  - College students in the United States face many health risks in what, for most,
      is their first extended stay away from home. Unhealthy diets, binge drinking, and
      stress can all contribute to the decreased health status of many 18-24 year olds
      attending college. Smoking on college campuses, however, is one factor that is
      not as often included in this list of risky behavior. Smoking and tobacco use is
      so prevalent that it is often considered the normal thing to do. To counter this
      belief, and hopefully provide a better way to equip Oklahoma students to lead
      tobacco-free lifestyles as adults, we have developed a thorough and pointed
      policy aimed at reducing tobacco use among the 18-24-year-old population. The
      Oklahoma statute entitled "Smoking in Public Places and Indoor Workplaces Act,"
      Title 63, specifically addresses smoking in educational facilities in Section 1
      1523 by giving educational facilities freedom to assign areas permissible for
      smoking outside buildings and during most activities. Part C of this section
      states, "Nothing in this section shall be construed to prohibit educational
      facilities from having more restrictive policies regarding smoking and the use of
      other tobacco products in the buildings or on the grounds of the facility." Part
      C is the premise of the following proposed policy. Outlined in this discussion
      will be the definition of the problem and basic rationale for such a policy,
      definition of educational facilities, an outline and communication of policy
      provisions, suggestions for assistance and cessation, types of enforcement,
      funding sources, and key players who need to be involved for effective
      application of this policy. Additionally discussed are the implications and
      limitations of a restricting policy on tobacco use.

PMID- 16629237
TI  - Patient Page. Smoking cessation.

PMID- 16629238
TI  - Medicare information.

PMID- 16629239
TI  - Endograft repair of abdominal aortic aneurysm with a right pelvic renal
      transplant.

PMID- 16629240
TI  - Resident work restrictions and the soul of the art.

PMID- 16629242
TI  - 2006 Medicare physician payment update and claims processing--questions and
      answers.

PMID- 16629241
TI  - Physician documentation essential for accurate coding and billing of excision of
      skin lesions.
AB  - Clear and precise documentation is essential to accurately code and bill for
      excision of benign or malignant skin lesions. Detailed documentation is crucial
      for capturing the full allowable reimbursement when the procedure involves more
      than a simple closure. For each lesion, only one type of removal may be reported,
      whether it is destruction, debridement, paring, curettement, shaving or excision.
      If an initial attempt to remove a lesion by a less invasive procedure is
      immediately followed by a more invasive lesion removal, only the more complex,
      definitive procedure may be billed. According to the Current Procedure
      Terminology manual (CPT), an excision of a skin lesion is defined as "full
      thickness (through the dermis) removal of a lesion, including margins, and
      includes simple (non-layered) closure when performed." Changes in recent years
      now allow code selection based on the greatest clinical diameter of the lesion
      plus the narrowest margin required for adequately excising the lesion, "based on
      the physician's judgment." According to CPT, the "measurement of lesion plus
      margin is made prior to excision".

PMID- 16629243
TI  - Cheating: an ethical concern for nursing educators.

PMID- 16629244
TI  - Should unlicensed workers be allowed to administer medications to residents in
      the state's community mental health homes?

PMID- 16629246
TI  - Putting Katrina in context.

PMID- 16629248
TI  - Polypharmacy and elders: a deadly combination.

PMID- 16629250
TI  - Payers hold the key to the NHIN.

PMID- 16629251
TI  - Exceptional success.

PMID- 16629252
TI  - Waiting room is closed.

PMID- 16629253
TI  - The all-in-one solution. A large-scale healthcare provider chooses one
      manufacturer to fulfill all of its IT needs.

PMID- 16629254
TI  - Setting the stage for growth.

PMID- 16629255
TI  - Transforming healthcare through patient empowerment.

PMID- 16629256
TI  - Lymphoma 2006: classification and treatment.
AB  - The past 20 years have brought significant advances in our ability to manage
      patients with non-Hodgkin's lymphoma. More precise classification systems,
      improvements in diagnosis and staging, and effective new treatments have improved
      outcomes and made cure a reasonable goal for many patients with these disorders.
      In this overview of the progress seen in the field over the past 2 decades, we
      describe a variety of advances for specific lymphomas, including diagnostic
      methods such as gene array studies and immunophenotyping and new treatment
      approaches.

PMID- 16629257
TI  - Identification and treatment of aggressive thyroid cancers. Part 1: subtypes.
AB  - Most thyroid cancers are slow-growing, easily treatable tumors with an excellent
      prognosis after surgical resection and targeted medical therapy. Unfortunately,
      10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an
      indolent course. Approximately one-third of patients with differentiated thyroid
      cancers will have tumor recurrences. Distant metastases are present in about 20%
      of patients with recurrent cancer. Approximately half of patients with distant
      metastases die within 5 years. The loss of the ability to concentrate radioiodine
      and produce thyroglobulin is a sign of dedifferentiation, which occurs in about
      30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is
      associated with poorer responses to conventional therapy and difficulty
      monitoring tumor burden. Clinicians must identify tumors with more aggressive
      biology and treat them accordingly with more aggressive regimens. Part 1 of this
      two-part article describes in detail the distinct types of thyroid cancer, as
      well as risk factors, outcomes, and prognostic factors, with a focus on thyroid
      cancers of follicular cell origin. Part 2, which will appear in next month's
      issue, covers risk assessment and staging, findings that suggest the presence of
      aggressive tumors, recurrent/metastatic disease, and the value of treatment with
      chemotherapy and external-beam radiotherapy. Experimental treatments utilizing
      molecular targets, redifferentiation agents, and gene therapy are covered briefly
      as well.

PMID- 16629258
TI  - Genetics of colorectal cancer.
AB  - Approximately 6% of colorectal cancers can be attributed to recognizable
      heritable germline mutations. Familial adenomatous polyposis is an autosomal
      dominant syndrome classically presenting with hundreds to thousands of
      adenomatous colorectal polyps that are caused by mutations in the APC gene.
      Adenomas typically develop in the midteens in these patients, and colorectal
      cancer is a virtual certainty if this condition is untreated. A low-penetrance
      susceptibility allele that is common in Jews from Eastern Europe, APC 11307K,
      confers a two-fold increased risk of colorectal cancer without the full
      expression of familial adenomatous polyposis. Biallelic mutations in the MYH gene
      are associated with an attenuated familial adenomatous polyposis phenotype. Lynch
      syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant
      disorder characterized by early onset of colorectal cancer with microsatellite
      instability. Mutations in mismatch repair genes lead to a lifetime colon cancer
      risk of 85% in these patients; carcinomas of the endometrium, ovary, and other
      organs also occur with increased frequency. Although adenomas are not
      characteristic of the hamartomatous polyp syndromes such as juvenile polyposis
      and Peutz-Jeghers syndrome, individuals with these diseases have a markedly
      increased risk of colorectal cancer relative to the general population. In this
      review, we will describe the phenotypes, genotypes, diagnosis, and management of
      hereditary colon cancer syndromes.

PMID- 16629259
TI  - Sexual health issues in men with cancer.
AB  - While the cancer patient may be affected by sexual dysfunction throughout the
      entire course of the disease, sexual health is largely underevaluated and
      undertreated. Sexual problems should be anticipated and patients should be
      actively screened as they are unlikely to initiate discussion on sexual issues.
      Cancer-related sexual dysfunction may involve several components, and an
      understanding of the underlying etiologies is essential to tailoring the
      appropriate treatment to the individual patient. This article reviews the
      numerous factors potentially involved in male sexual dysfunction associated with
      a variety of cancers.

PMID- 16629260
TI  - Retrospective and perspectives of thermophilic anaerobic digestion: Part II.

PMID- 16629261
TI  - Performance evaluation of a 'sequential-batch' temperature-phased anaerobic
      digestion (TPAD) scheme for producing Class A biosolids.
AB  - Laboratory studies were conducted to evaluate the performance and operational
      stability of a Temperature-Phased Anaerobic Digestion (TPAD) system modified to
      operate in the sequential-batch mode. The system fed with a 40:60 mixture (dry
      weight) of primary sludge (PS) and waste activated sludge (WAS) at 5.5% solids
      showed stable performance with minimum variation in operational parameters such
      as biogas production, VFA to alkalinity ratio, pH, and foam accumulation at
      system retention times as short as 12 days. The maximum volatile solids removal
      (VSR) of 52.5% was achieved at a system retention time of 16 days. The system did
      not show any effects of "shock loading" at the retention times studied and
      outperformed a "conventional" mesophilic system operated at a longer retention
      time. The system was effective in reducing the densities of pathogenic indicator
      organisms in the biosolids to levels lower than those specified by U.S. EPA for
      Class A designation.

PMID- 16629262
TI  - Microbial source tracking of Escherichia coli in a constructed wetland.
AB  - Little information has been gathered on the effect of avian species on the
      microbial water quality in constructed wetlands. To address this concern, fecal
      pollution from nonpoint and point sources was evaluated in a constructed wetland
      in Tolleson, Arizona. Antibiotic resistance profiling and biochemical
      fingerprinting were performed on 325 Escherichia coli isolates, collected from
      key points in the wetlands. Multivariate statistical analysis was used to
      interpret the data for samples collected on October 3 and December 12, 2000, and
      January 16, 2001. It was found that the passerine population was the major source
      of the Escherichia coli in the water samples collected in the wetlands on October
      3 and December 12, 2000, whereas the regrowth in the treated municipal wastewater
      was the main source on January 16, 2001. This information is useful in providing
      data for operators in the monitoring of wetlands created for wastewater treatment
      and wildlife habitat.

PMID- 16629263
TI  - Municipal-wastewater treatment using upflow-anaerobic filters.
AB  - Three 12.5-L upflow-anaerobic filters (AF), with ceramic-saddle, plastic-ring,
      and crushed-stone packing, were used to evaluate the sustained treatment of
      municipal wastewater. The reactors were initially fed dogfood-fortified
      wastewater and then raw municipal wastewater, and operated at 25.4 degrees C (32
      months) and 15.5 degrees C (2 months). During 23 months, the AF units treated
      municipal wastewater (mean chemical oxygen demand [COD] 442 mg/L and total
      suspended solids [TSS] 247 mg/L), the hydraulic retention time (HRT) ranged from
      3.1 to 0.30 d (empty bed), and the organic loading rate ranged from 0.115 to 1.82
      kg COD/m3d. At the higher temperature and an HRT (void volume) of 1.0 d, COD and
      TSS removals ranged from 74 to 79% and 95 to 96%, respectively; however,
      efficiencies declined substantially at HRT values less than 0.4 d. Reactor
      performance, under the same hydraulic and organic loadings, deteriorated with
      time and was adversely affected by lower temperature.

PMID- 16629264
TI  - Cycling of volatile organic sulfur compounds in anaerobically digested biosolids
      and its implications for odors.
AB  - The objectives of this research were to elucidate the mechanisms for production
      and degradation of volatile organic sulfur compounds (VOSCs), key odor causing
      compounds produced by biosolids. These compounds included methanethiol (MT),
      dimethyl sulfide (DMS), and dimethyl disulfide (DMDS). A series of experiments
      were used to probe various pathways hypothesized to produce and degrade these
      VOSCs. The production of MT was found to mainly occur from degradation of
      methionine and the methylation of hydrogen sulfide. DMS was formed through the
      methylation of MT. DMDS was formed by MT oxidation. All three of the VOSCs were
      readily degraded by methanogens and a cyclic pathway was proposed to describe the
      production and degradation of VOSCs. The research demonstrated that the main
      source of VOSCs was the biodegradation of protein within the biosolids and the
      results provided a framework for understanding the production of odor from
      anaerobically digested sludges before and after dewatering.

PMID- 16629265
TI  - Transformation of molecular weight distributions of dissolved organic carbon and
      UV-absorbing compounds at full-scale wastewater-treatment plants.
AB  - The molecular-weight distribution (MWD) of wastewater dissolved-organic carbon
      (DOC) was determined in samples from seven full-scale wastewater-treatment plants
      (WWTPs) that use different biological treatments (air activated sludge [air-AS],
      pure-oxygen AS [O2-AS], and trickling filters). The research objective was to
      determine how different biological treatments influenced the MWD of wastewater
      DOC. Primary sedimentation effluent DOC from most of the WWTPs exhibited a skewed
      distribution toward the low-molecular-weight fraction (MWF) (40 to 50%, < 0.5 K
      Daltons [KDa]). The Air-AS effluent DOC exhibited a centrally clustered
      distribution, with the majority of DOC in the intermediate MWF (0.5 to 3 KDa).
      The O2-AS effluent DOC exhibited a skewed distribution toward the high MWF (> 3
      KDa). The removal of DOC by air- and O2-AS bacteria followed trends predicted by
      a macromolecule degradation model. Trickling-filter effluent DOC exhibited a
      skewed distribution toward the high MWF (50% DOC, > 3 KDa).

PMID- 16629266
TI  - Kinetic studies of adsorption of lead(ll) from aqueous solution by wine
      processing waste sludge.
AB  - A waste sludge produced from a wine-processing wastewater treatment process was
      used as an adsorbent to removal of heavy metal-lead(II) from aqueous solution.
      Results of kinetic experiments demonstrated that the adsorption was effective and
      rapid. Four different kinds of adsorption kinetic models (i.e., pseudo-first
      order, pseudo-second-order, and two intra-particular mass diffusion models) were
      used to investigate the adsorption mechanisms. A normalized standard deviation
      was used to find the best adsorption kinetic model for the removal of lead(ll) by
      the sludge. The comparison shows that the kinetic adsorption data can be well
      described by the pseudo-second-order adsorption model and that sorption might be
      a rate-limiting control. The adsorption-rate constant and adsorption capacity of
      pseudo-second-order adsorption equation were calculated. The parameters (initial
      lead(II) concentration, sludge-particle size, and sludge dosages), which affect
      the adsorption capacity of sludge, were discussed by using the pseudo-second
      order adsorption equation.

PMID- 16629267
TI  - Optimal design of predenitrification systems.
AB  - A coupled model of biological and settling phases aimed at optimal design of
      predenitrification systems is presented. Each unknown is obtained in explicit
      form, and is expressed as a function of the system's required performance. A
      model, taking into account both suspended and dissolved substrates, is adopted
      for the biological phase, while the limiting solid flux theory is assumed for the
      design of the settling phase. Finally, a relationship correlating the two phases
      is obtained expressing opportunely the sludge recycle flow and the sludge waste
      flow, without recourse to empirical parameters. The effect of different influent
      and effluent wastewater characteristics on the model's results is also analyzed.

PMID- 16629268
TI  - Kinetics and stoichiometry of aerobic sulfide oxidation in wastewater from sewers
      effects of pH and temperature.
AB  - Kinetics and stoichiometry of aerobic chemical and biological sulfide oxidation
      in wastewater from sewer networks were studied. In this respect, the effects of
      temperature and pH were investigated in the ranges 10 to 20 degrees C and 5 to 9,
      respectively. The temperature dependency of sulfide oxidation kinetics was
      described using an Arrhenius relationship. The effect of pH on the rate of
      chemical sulfide oxidation is related to the dissociation of hydrogen sulfide
      (H2S) to hydrogen sulfide ion (HS(-)), with HS(-) being more readily oxidized
      than H2S. Biological sulfide oxidation exhibited the highest rates at ambient
      wastewater pH, and the reaction was inhibited at both low and high pH values.
      Chemical sulfide oxidation was found to produce thiosulfate and sulfate, while
      elemental sulfur was the main product of biological sulfide oxidation. Based on
      the investigations, general rate equations and stoichiometric constants were
      determined, enabling the processes to be incorporated to conceptual sewer process
      models.

PMID- 16629269
TI  - Water quality improvement through bioretention media: nitrogen and phosphorus
      removal.
AB  - High nutrient inputs and eutrophication continue to be one of the highest
      priority water quality problems. Bioretention is a low-impact development
      technology that has been advocated for use in urban and other developed areas.
      This work provides an in-depth analysis on removal of nutrients from a synthetic
      stormwater runoff by bioretention. Results have indicated good removal of
      phosphorus (70 to 85%) and total Kjeldahl nitrogen (55 to 65%). Nitrate reduction
      was poor (< 20%) and, in several cases, nitrate production was noted. Variations
      in flowrate (intensity) and duration had a moderate affect on nutrient removal.
      Mass balances demonstrate the importance of water attenuation in the facility in
      reducing mass nutrient loads. Captured nitrogen can be converted to nitrate
      between storm events and subsequently washed from the system. Analysis on the
      fate of nutrients in bioretention suggests that accumulation of phosphorus and
      nitrogen may be controlled by carefully managing growing and harvesting of
      vegetation.

PMID- 16629270
TI  - Ultraviolet disinfection of fecal coliform in municipal wastewater: effects of
      particle size.
AB  - Suspended solids interfere with the efficiency of disinfection using UV radiation
      by decreasing the rate of disinfection and inducing tailing. However,
      conventional measures of solids (total suspended solids, turbidity, and UV
      transmittance) do not adequately predict the presence or degree of these effects.
      Bacteria and viruses can become associated with particles in wastewater. A
      fractionation technique was developed to separate particle-associated bacteria
      into three fractions, based on particle size. The results show that the degree to
      which particles interfere with UV disinfection efficiency is dependent on
      particle size. The small size fraction (< 5 microm) consistently produced a
      statistically significant faster disinfection rate than the large fraction (> 20
      microm), with the unfiltered sample and the medium fraction (particles > 5
      microm, but < 20 microm) between the two extremes. Tailing also was observed only
      in the large fraction. Correlations between the disinfection rate constant and
      the percentage of large fraction bacteria of a sample were good.

PMID- 16629271
TI  - Effect of biopolymer on the dewatering characteristics of autothermal
      thermophilic aerobic digestion of sludges.
AB  - Autothermal thermophilic aerobic digestion of sludge is known to produce poorly
      dewatering sludges. Laboratory studies were conducted to investigate the reasons
      for the poor dewatering. It was found that, during digestion, proteins and
      polysaccharides were released into solution, and that these could be linked to
      the deterioration in dewatering. The biopolymer release was accompanied by an
      increase in the monovalent-to-divalent (M/D) cation ratio. The degree to which
      the M/D caused deterioration of the sludges depended on the presence of iron in
      sludge. When the iron content was high, the release of protein and
      polysaccharides was low. When iron was low, the release of protein and
      polysaccharides increased linearly with the M/D ratio. The dose of conditioning
      chemicals, cationic polymer or ferric chloride, was related to the amount of
      colloidal biopolymer present in solution. The findings suggest that the addition
      of iron during the digestion process has the potential to produce better
      dewatering sludges.

PMID- 16629272
TI  - Enhanced desorption of RDX from granular activated carbon.
AB  - Several methods (cosolvents, surfactants, and cyclodextrins) were compared for
      improving desorption of a high explosive, RDX, from granular activated carbon
      (GAC). In batch desorption tests, 3% of the adsorbed RDX (initially 71.1 mg RDX/g
      GAC) was desorbed by water over 11 days, compared to 92.6% desorption by 100%
      ethanol. Solutions of ethanol or methanol in water also effectively desorbed RDX,
      although methanol was somewhat less effective than ethanol. Sodium dodecyl
      sulfate desorbed as much as 70% of the adsorbed RDX, while the non-ionic
      surfactants Tween 80, Triton X-100, and Brij 30 desorbed as much as 42 to 51% of
      the RDX. In continuous flow column tests, GAC was partially regenerated. One-half
      of the adsorbed RDX was desorbed by 2100 bed volumes (BV) of 10% ethanol,
      compared to the 22 500 BV of buffered water. Column modeling indicated that
      competitive adsorption and altered equilibrium conditions combined to enhance RDX
      desorption.

PMID- 16629273
TI  - Comparison of dissolved-organic-carbon residuals from air- and pure-oxygen
      activated-sludge sequencing-batch reactors.
AB  - Literature shows that full-scale pure-oxygen activated sludge (O2-AS) wastewater
      treatment plants (WWTPs) generate effluents with higher dissolved-organic carbon
      (DOC) concentrations and larger high-molecular-weight fractions compared to air
      activated-sludge (Air-AS) WWTP effluents. The purpose of this paper was to
      evaluate how gas supplied (air vs. pure oxygen) to sequencing-batch reactors
      affected DOC transformations. The main conclusions of this paper are (a) O2-AS
      effluent DOC is more refractory than air-AS effluent DOC; and (b) O2-AS systems
      may have higher five-day biochemical oxygen demand removals than air-AS systems;
      however, in terms of COD and DOC removal, air-AS systems are better than O2-AS
      systems. Analysis of a database from side-by-side O2- and air-AS pilot tests from
      literature supported these observations.

PMID- 16629274
TI  - Survival of total coliforms in lawn irrigated with secondary wastewater and
      chlorinated effluent in the Mediterranean region.
AB  - Pregrown, two-month-old lawn was layered in 12 large square pots with an area of
      0.25 m2 each, filled with a mixture of topsoil, peat, and sand. In late July, in
      the heart of the Mediterranean summer, the pots were divided into two groups,
      with six pots per group. On four different occasions, the pots in each group were
      sprinkled (surface irrigation) with 2 L of either secondary-treated wastewater
      (STW, group A) or chlorinated effluent (CHE, group B). Wastewater application
      always took place at 0700 hours. Samples of the surface soil and grass from each
      pot were collected at the following times: before irrigation, immediately after
      irrigation, two hours later (0900 hours), and four hours later (1100 hours). In
      the samples collected, the number of total coliforms per gram was measured using
      standard microbiological analyses. Temperature and sunlight intensity were also
      monitored. There was an increase in the coliforms population in soil and grass
      samples of both groups immediately after the wastewater application. In group A,
      the mean number of coliforms recorded in the soil samples reached mean values
      higher than 5000 cfu/g compared to 312 cfu/g recorded before application. The
      increase in group B was smaller but still significant. Two hours later, the
      number of coliforms was reduced substantially in all samples (e.g., group A, soil
      samples 477 cfu/g). Coliform inactivation is thought to result from the effect of
      temperature and mainly sunlight. However, four hours after application (1100
      hours), there was a noticeable increase in the coliform number again, in all
      sample categories of both groups. Coliform reactivation could be a result of
      shadowing effect resulting from the thick foliage of the grass, where the
      microorganisms were protected by the sunlight radiation and regrowth in a
      friendly environment (especially of the soil) where moisture and nutrients were
      present. This, in addition to the fact that coliforms seemed to retain a sizable
      population between applications, results in three conclusions: (1) coliforms can
      survive in grass and soil for a substantial period of time, recovering from the
      destructive effect of chlorination, (2) use of STW, even during the Mediterranean
      summer, could result in a substantial "contamination" of lawns, without any proof
      that sun and temperature can reduce the coliform number, and (3) intense sunlight
      (up to 68 000 lux) was far more effective in coliform suppression than elevated
      temperature (up to 38 degrees C).

PMID- 16629276
TI  - Update to HR.1.20.

PMID- 16629275
TI  - The Joint Commission announces the 2006 National Patient Safety Goals and
      requirements.

PMID- 16629277
TI  - The next transformation: clinical education.

PMID- 16629278
TI  - The teaching effectiveness of standardized patients.
AB  - Teaching nursing students therapeutic communication skills begins in the
      classroom and extends to the clinical environment. The usual method of
      instruction consists of random patient encounters observed by faculty and
      measures of competence that rely on paper-and-pencil tests. Using standardized
      patients (SPs) offers an alternative approach to the traditional method of
      teaching. Standardized patients are individuals who have been carefully trained
      to present an illness or scenario in a standardized, unvarying manner. This pilot
      study compared use of SPs with the usual method of instruction in a class of
      undergraduate nursing students. Results indicated that students who participated
      in the SP method overwhelmingly described the experience as positive, creative,
      and meaningful. No significant differences were found between the two groups on
      measures of interpersonal skills, therapeutic communication skills, and knowledge
      of depression

PMID- 16629279
TI  - Mind-mapped care plans: integrating an innovative educational tool as an
      alternative to traditional care plans.
AB  - Teaching nursing students how to think critically when planning patient care is
      vital to their professional success. Traditionally, the nursing care plan has
      been used to apply steps of the nursing process in planning patient care.
      However, nursing has evolved into a more complex profession that requires
      expanded ways of thinking and reasoning beyond the linear methods used in the
      past. Mind-mapped care plans provide an alternative method of teaching holistic,
      patient-centered care. This article describes the process used to integrate the
      mind-mapped care plan as an innovative educational tool, as well as formative and
      summative outcomes of its use.

PMID- 16629280
TI  - Second-year baccalaureate nursing Students' decision making in the clinical
      setting.
AB  - This qualitative, intrinsic case study explored the decision-making activities of
      baccalaureate nursing students in the second year of a 4-year program. It sought
      to discover how second-year students determine the need to make a clinical
      decision, how they respond to a pending clinical decision, the types of decisions
      made in the clinical setting, and the factors that enhance or impede decision
      making. The study involved 12 students, all of whom were enrolled in their first
      clinical rotation on an inpatient unit and completed journals and interviews.
      Inductive analysis revealed three key encounters that demonstrated students'
      decision making: encounters with the patient, nursing staff, and clinical tutor.
      Each encounter revealed an emotion-based and knowledge-based response to various
      clinical situations. Decisions were evident within each of the three encounters.
      Implications for curriculum development and clinical tutors are described.

PMID- 16629281
TI  - Modeling mentorship and collaboration for BSN and MSN students in a community
      clinical practicum.
AB  - This project uses an innovative approach to facilitate mentorship and
      collaboration among BSN and MSN students within a community health practice
      environment. In a pilot test using a clinical model, graduate and undergraduate
      students were matched as mentors and mentees. These students worked with faculty
      and clinic staff to develop a mentorship network and effective collaborative
      practice within an interdisciplinary team, while implementing health promotion
      education programs for clinic clients. Ten students participated in the process
      and evaluated it as effective and valuable in the development of professional
      roles, as well as in validating the model variables used in the project.

PMID- 16629282
TI  - An acute hospital ward, densely populated with students during a 12-week clinical
      study period.
AB  - This article presents some thoughts and ideas about a different way to organize
      clinical studies for nursing students. The model involved a large group (12 to
      15) of third-year nursing students taking their 12-week clinical study period on
      the same acute geriatric hospital ward. Difficulties with finding enough clinical
      study venues, together with a belief in peer learning and situated learning as
      important for learning, were the main reasons for trying out a model with many
      students doing clinical studies on the same ward. The model has been used twice,
      and evaluations showed that students believed the clinical study period had given
      them the opportunity to develop their nursing competence. Most of the students
      experienced cooperation with other students as self-developing. Staff experienced
      this model as a positive influence on students' professional development and as
      stimulating for the professionalism of the ward.

PMID- 16629283
TI  - An agency-financed capstone experience for graduating seniors.
AB  - Capstone experiences are increasingly expected at the conclusion of undergraduate
      curricula. For some programs, the capstone project is a thesis or paper; for
      nursing, a clinical experience that synthesizes prior learning is the norm. In
      Kentucky, nursing programs are required to provide the opportunity for students
      to spend 120 hours in a clinical setting just prior to graduation. The authors
      evaluated an innovative approach to providing these hours during the last 7 weeks
      of the nursing program.

PMID- 16629284
TI  - Managing conflict in the clinical setting: a case scenario.

PMID- 16629285
TI  - Using experiential learning: facilitating hands-on basic patient skills.

PMID- 16629286
TI  - Teaching students to promote positive patient change.

PMID- 16629287
TI  - The CARE case study method for teaching community health nursing.

PMID- 16629288
TI  - Semantic feature production norms for a large set of living and nonliving things.
AB  - Semantic features have provided insight into numerous behavioral phenomena
      concerning concepts, categorization, and semantic memory in adults, children, and
      neuropsychological populations. Numerous theories and models in these areas are
      based on representations and computations involving semantic features.
      Consequently, empirically derived semantic feature production norms have played,
      and continue to play, a highly useful role in these domains. This article
      describes a set of feature norms collected from approximately 725 participants
      for 541 living (dog) and nonliving (chair) basic-level concepts, the largest such
      set of norms developed to date. This article describes the norms and numerous
      statistics associated with them. Our aim is to make these norms available to
      facilitate other research, while obviating the need to repeat the labor-intensive
      methods involved in collecting and analyzing such norms. The full set of norms
      may be downloaded from www.psychonomic.org/archive.

PMID- 16629289
TI  - Expanding the universe of categorical syllogisms: a challenge for reasoning
      researchers.
AB  - Syllogistic reasoning, in which people identify conclusions from quantified
      premise pairs, remains a benchmark task whose patterns of data must be accounted
      for by general theories of deductive reasoning. However, psychologists have
      confined themselves to administering only the 64 premise pairs historically
      identified by Aristotle. By utilizing all combinations of negations, the present
      article identifies an expanded set of 576 premise pairs and gives the valid
      conclusions that they support. Many of these have interesting properties, and the
      identification of predictions and their verification will be an important next
      step for all proponents of such theories.

PMID- 16629290
TI  - Comparison of four scoring methods for the reading span test.
AB  - This study compared four common methods for scoring a popular working memory span
      task, Daneman and Carpenter's (1980) reading span test. More continuous measures,
      such as the total number of words recalled or the proportion of words per set
      averaged across all sets, were more normally distributed, had higher reliability,
      and had higher correlations with criterion measures (reading comprehension and
      Verbal SAT) than did traditional span scores that quantified the highest set size
      completed or the number of words in correct sets. Furthermore, creation of
      arbitrary groups (e.g., high-span and low-span groups) led to poor reliability
      and greatly reduced predictive power. It is recommended that researchers score
      span tasks with continuous measures and avoid post hoc dichotomization of working
      memory span groups.

PMID- 16629291
TI  - Revised Space Fortress: a validation study.
AB  - We describe briefly the redevelopment of Space Fortress (SF), a research tool
      widely used to study training of complex tasks involving both cognitive and motor
      skills, to be executed on current-generation systems with significantly extended
      capabilities, and then compare the performance of human participants on an
      original PC version of Space Fortress (SF) with the revised Space Fortress (RSF).
      Participants trained on SF or RSF for 10 sets of eight 3-min practice trials and
      two 3-min test trials. They then took tests involving retention, resistance to
      secondary task interference, and transfer to a different control system. They
      then switched from SF to RSF or from RSF to SF for 2 sets of final tests and
      completed rating scales comparing RSF and SE Slight differences were predicted on
      the basis of a scoring error in the original version of SF used and on slightly
      more precise joystick control in RSF. The predictions were supported. The SF
      group started better but did worse when they transferred to RSE Despite the
      disadvantage of having to be cautious in generalizing from RSF to SF, we conclude
      that RSF has many advantages, which include accommodating new PC hardware and new
      training techniques. A monograph that presents the methodology used in creating
      RSF, details on its performance and validation, and directions on how to download
      free copies of the system may be downloaded from www.psychonomic.org/archive/.

PMID- 16629292
TI  - Application of video glasses for sustained affective picture presentations: a
      comparison with video projector presentations.
AB  - Video glasses have previously been reported to be an effective instrument for
      emotion induction or for reducing pain perception. In the present study, we
      assessed the application of video glasses within the affective picture viewing
      paradigm. Possible advantages of this new method were tested by a comparison with
      a commonly used video projector. Twenty-four participants viewed sustained
      picture series of pleasant, neutral, and unpleasant valence with video glasses
      and with a projector on different days. Affective report, heart rate (HR), and
      skin conductance level were measured. The results showed that the video glasses
      presentation mode is not generally superior to the projector mode. Instead,
      typical responses to prolonged presentations of emotional pictures were obtained
      across both modalities with valence-modulated pleasure ratings and with an
      arousal modulation for arousal ratings, skin conductance level, and HR. These
      results suggest that video glasses are as useful for presenting prolonged
      affective picture series as are projectors. Specific contexts in which the
      application of video glasses is preferential are discussed.

PMID- 16629293
TI  - The representation of ontological category concepts as affected by healthy aging:
      normative data and theoretical implications.
AB  - Attributes associated with concept representations, such as familiarity,
      typicality, and age of acquisition, have been shown to be important influences on
      lexical-semantic processing. In most previous studies of healthy and pathological
      aging, these attributes are not equated for younger and older adults separately
      on the stimuli used. In this study, normative data were collected to test whether
      there exist any age differences in these attributes. The results demonstrate that
      the ratings given by younger and older adults on natural and manmade category
      items correlated positively. However, age differences were also apparent, whereby
      older adults provided higher ratings overall than younger adults. Suggestions and
      hypotheses are presented to explain this pattern of age differences, which relate
      to how category concepts may be represented by healthy younger and older adults.
      Also, the possible implications for these differential age ratings on lexical
      semantic processing are discussed. The age differences apparent in this study
      demonstrate the need to consider age-appropriate normative ratings in the
      selection of stimuli for use in lexical-semantic processing studies of aging, and
      the normative data presented provide a means of equating category stimuli. The
      complete list of all the means is available at www.psychonomic.org/archive.

PMID- 16629294
TI  - Emotional category data on images from the International Affective Picture
      System.
AB  - The International Affective Picture System (IAPS) is widely used in studies of
      emotion and has been characterized primarily along the dimensions of valence,
      arousal, and dominance. Even though research has shown that the IAPS is useful in
      the study of discrete emotions, the categorical structure of the IAPS has not
      been characterized thoroughly. The purpose of the present project was to collect
      descriptive emotional category data on subsets of the LAPS in an effort to
      identify images that elicit onediscrete emotion more than others. These data
      reveal multiple emotional categories for the images and indicate that this image
      set has great potential in the investigation of discrete emotions. This article
      makes these data available to researchers with such interests. Data for all the
      pictures are archived at www.psychonomic.org/archive/.

PMID- 16629295
TI  - Normative data for semantically associated Spanish word lists that create false
      memories.
AB  - The present study provides norms for Spanish word lists that have been used to
      create false memories in native speakers of Spanish. The word lists reported are
      based on the Roediger and McDermott (1995) lists that have been used extensively
      to examine illusory memories. We employed Roediger and McDermott's critical
      lures, translated them into Spanish, and created semantically associated Spanish
      word lists by testing native Spanish speakers. The resulting lists were then
      normed with additional native Spanish speakers. Overall, the participants
      recalled 53% of the list items and 32% of the critical lures with the word lists
      developed. In addition, 74% of the list items and 69% of the critical lures were
      recognized by the participants. The present study adds to the literature by
      providing a set of Spanish lists that can be used by researchers interested in
      evaluating false memories in individuals who speak Spanish. These norms may be
      downloaded from www.psychonomic.org/archive.

PMID- 16629296
TI  - A program for assessing body image disturbance using adjustable partial image
      distortion.
AB  - Body image disturbance has been one of the most widely studied areas in the
      literature on eating disorders. Some of the tasks designed to assess it have been
      used to estimate the sizes of specific parts of the body, whereas others have
      served to make estimations of overall body size. In recent years, the
      introduction of innovative computing procedures has allowed the two approaches to
      be combined and has made their application more straightforward. The program we
      describe here (Body Image Assessment Software, or BIAS) evaluates body image
      distortions and body dissatisfaction via the on-screen presentation of a scale
      image, the different components of which can be modified by the patient. The
      program was developed using Microsoft Access 2000 and Visual Basic for
      applications. It can be run on any computer with Windows and Microsoft Access
      2000 or Microsoft Access 2000 RunTime, which makes it particularly easy to use
      and enables direct analysis of the recorded data through the use of applications
      such as SPSS.

PMID- 16629297
TI  - Objective versus estimated age of word acquisition: a study of 202 Italian
      children.
AB  - We provide objective data concerning the age of acquisition (AoA) of words from
      202 Italian children 34-69 months of age. We investigated picture naming with 80
      concrete words belonging to eight semantic categories that are included in a
      widely used battery for the study of naming and semantic memory. For each word,
      we calculated three different indices: two directly expressing the age at which a
      picture was given the correct name by at least 75% of the subjects, and one
      expressing the overall percentage of our children who were correct in the task.
      (For the latter index, we provide separate values for boys and girls.). The
      correlation between objective indices of AoA and adult estimates culled from the
      literature was not very high. Moreover, objective indices showed low correlations
      with frequency and familiarity, in contrast to adult ratings. We conclude that
      adult estimates of AoA present validity problems and should be used with caution.
      The full set of stimuli is available at www.psychonomic.org/archive.

PMID- 16629298
TI  - Recommended housing conditions and test procedures can interact to obscure a
      significant experimental effect.
AB  - Routine animal husbandry variables, such as group housing of mice and the order
      of testing of cage-mates, are currently viewed to be essentially neutral with
      respect to the outcome of most, if not all, animal-based experiments, including
      those that utilize behavioral measurements. During the course of experiments that
      have utilized the elevated plus-maze to examine the ability of a bacterial
      challenge of mice to induce anxiety-like behavior, due to the activation of
      various cytokine pathways, we followed the recommendation of laboratory animal
      care staff to house the mice in pairs. Whenwe testedthe members of the pairs
      successively, it was found, for the first experimental set, that the behavior
      that reflects anxiety (time in closed arms) of the first-tested animal differed
      from that of the second-tested animal for both the experimental and the control
      animals and, critically, that these changes were in the opposite directions for
      the controls and the experimental animals, thus obscuring the effect of the
      experimental manipulation. A second, independent experimental set also obtained a
      significant effect for the order of testing effect in the bacterial-challenged
      group, but not in the saline control group, although a similar trend was evident
      in this group as well. These results indicate that special care should to be
      taken in implementing housing recommendations and that preliminary tests may be
      necessary to ensure that housing conditions do not interact with tests of the
      phenomenon under experimental investigation.

PMID- 16629299
TI  - A fiber-optic system for recording skin conductance in the MRI scanner.
AB  - The acquisition of the skin conductance response (SCR) during functional magnetic
      resonance imaging (fMRI) raises significant safety issues, as well as practical
      ones, which need to be addressed in order for these experiments to be conducted
      safely and successfully. Metallic and conductive wires in the presence of time
      varying gradient magnetic fields such as those present in fMRI experiments may
      induce heating, as well as electric fields, in these components and, if in
      contact with the subject, could produce severe burns and electric shocks.
      Moreover, these metallic and conductive components can significantly distort the
      magnetic field, resulting in image artifacts. A system for recording the SCR in
      humans simultaneously with fMRI is presented. The device is a fiber-optic-based
      transducer, which records the SCR from two fingers of the same hand, using
      electrodes containing inline radio frequency (RF) suppression filters and
      protective resistive loads. The fiber-optic SCR transducer was tested using 1.5
      and 3.0 Tesla MRI scanners running EPI sequences. This system was able to safely
      record SCRs free of RF interference during an fMRI experiment, and the fiber
      optic design of the transducer eliminated any artifacts on the MRI scan.

PMID- 16629300
TI  - BuscaPalabras: a program for deriving orthographic and phonological neighborhood
      statistics and other psycholinguistic indices in Spanish.
AB  - This article describes a Windows program that enables users to obtain a broad
      range of statistics concerning the properties of word and nonword stimuli in
      Spanish, including word frequency, syllable frequency, bigram and biphone
      frequency, orthographic similarity, orthographic and phonological structure,
      concreteness, familiarity, imageability, valence, arousal, and age-of-acquisition
      measures. It is designed for use by researchers in psycholinguistics,
      particularly those concerned with recognition of isolated words. The program
      computes measures of orthographic similarity online, with respect to either a
      default vocabulary of 31,491 Spanish words or a vocabulary specified by the user.
      In addition to providing standard orthographic and phonological neighborhood
      measures, the program can be used to obtain information about other forms of
      orthographic similarity, such as transposed-letter similarity and embedded-word
      similarity. It is available, free of charge, from the following Web site:
      www.maccs.mq.edu.au/-colin/B-Pal.

PMID- 16629301
TI  - Confirmatory factor analysis using Microsoft Excel.
AB  - This article presents a method for using Microsoft (MS) Excel for confirmatory
      factor analysis (CFA). CFA is often seen as an impenetrable technique, and thus,
      when it is taught, there is frequently little explanation of the mechanisms or
      underlying calculations. The aim of this article is to demonstrate that this is
      not the case; it is relatively straightforward to produce a spreadsheet in MS
      Excel that can carry out simple CFA. It is possible, with few or no programming
      skills, to effectively program a CFA analysis and, thus, to gain insight into the
      workings of the procedure.

PMID- 16629302
TI  - A mean for all seasons.
AB  - The averaging of scores differs from the averaging of numbers in that behavioral
      issues are built into scores. The behavioral issues are the weight attached to a
      score and the metric on which the scores have been gathered. A single equation is
      proposed, derived from Aczel's (1966) model of the quasilinear mean, that
      encompasses the standard measures of central tendency. The equation allows for
      differential weighting of scores and also addresses the metric issue by
      incorporating response transformation.

PMID- 16629303
TI  - Enhancing dynamic graphical analysis with the Lisp-Stat language and the ViSta
      statistical program.
AB  - Presented is a sample of computerized methods aimed at multidimensional scaling
      and psychometric item analysis that offer a dynamic graphical interface to
      execute analyses and help visualize the results. These methods show how the Lisp
      Stat programming language and the ViSta statistical program can be jointly
      applied to develop powerful computer applications that enhance dynamic graphical
      analysis methods. The feasibility of this combined strategy relies on two main
      features: (1) The programming architecture of ViSta enables users to add new
      statistical methods as plug-ins, which are integrated into the program
      environment and can make use of all the functions already available in ViSta
      (e.g., data manipulation, editing, printing); and (2) the set of powerful
      statistical and graphical functions integrated into the Lisp-Stat programming
      language provides the means for developing statistical methods with dynamic
      graphical visualizations, which can be implemented as ViSta plug-ins.

PMID- 16629304
TI  - Measuring health beliefs on the Internet: A comparison of paper and Internet
      administrations of the Multidimensional Health Locus of Control Scale.
AB  - A growing number of studies have supported the use of unidimensional psychometric
      test instruments administered via the Internet; however, support for the use of
      multidimensional scales is weak. The present study compares paper and Internet
      administrations of the Multidimensional Health Locus of Control (MHLC) Scale
      (Wallston & Wallston, 1981). In terms of reliabilities and factor structures, the
      Internet data were found to be at least as good as the paper data. MHLC scores
      were comparable for paper and Internet administrations, although the Internet
      sample scored significantly lower on the Powerful Others subscale. Overall, the
      results show that administration of the MHLC Scale via the Internet can produce
      data comparable to that obtained by pen-and-paper methods. However, it is
      concluded that generalization of these findings beyond the psychometric test
      instrument and sampling procedures used here is not warranted.

PMID- 16629305
TI  - Generic HTML Form Processor: A versatile PHP script to save web-collected data
      into a MySQL database.
AB  - The customizable PHP script Generic HTML Form Processor is intended to assist
      researchers and students in quickly setting up surveys and experiments that can
      be administered via the Web. This script relieves researchers from the burdens of
      writing new CGI scripts and building databases for each Web study. Generic HTML
      Form Processor processes any syntactically correct HTML forminput and saves it
      into a dynamically created open-source database. We describe five modes for usage
      of the script that allow increasing functionality but require increasing levels
      of knowledge of PHP and Web servers: The first two modes require no previous
      knowledge, and the fifth requires PHP programming expertise. Use of Generic HTML
      Form Processor is free for academic purposes, and its Web address is
      www.goeritz.net/brmic.

PMID- 16629306
TI  - The effect of lectins on Cryptosporidium parvum oocyst in vitro attachment to
      host cells.
AB  - The influence of lectins on Cryptosporidium parvum oocyst agglutination and on
      attachment to both fixed Madin Darby Canine Kidney (MDCK) cells and fixed HCT-8
      (human colorectal epithelial) cells was examined. Oocyst cell wall
      characteristics were examined by transmission electron microscopy. Lectin-free
      oocysts were shown to adhere equally to both MDCK cells and HCT-8 cells. In MDCK
      cells, the addition of 1-25 microg/ml Codium fragile lectin, 10 microg/ml Maclura
      pomifera lectin, 10 microg/ml Helix pomatia lectin, and 10-200 microg/ml
      Artocarpus integrifolia lectin significantly increased attachment to at least 1
      of the cell cultures as compared to oocysts incubated without any lectin. The
      lectin-enhanced attachment was reversed by co-incubation of lectin treated
      oocysts with 250 mM of each specific sugar (for a given lectin). In agglutination
      assays, concentrations as low as 0.5 microg/ml of C. fragile, M. pomifera, and A.
      integrifolia lectin agglutinated oocysts within 60 min. Finally, in TEM samples,
      colloidal gold conjugated-lectins from A. integrifolia, C. fragile, H. pomatia,
      and M. pomifera attached to oocysts, and this could be competitively inhibited by
      a lectin-specific sugar. This suggests that C. parvum oocysts are highly reactive
      to N-acetyl galactosamine-binding lectins and that the presence of N-acetyl
      galactosamine containing molecules on oocysts can potentially help in oocyst
      attachment to host cells.

PMID- 16629307
TI  - Ubiquitous variability in the prevalence of Trichobilharzia stagnicolae
      (Schistosomatidae) infecting Stagnicola emarginata in three northern Michigan
      lakes.
AB  - During 4 consecutive collecting seasons from 1998 through 2001, 77,326 common
      beach snails (Stagnicola emarginata, Lymnaeidae) were examined for infections by
      Trichobilharzia stagnicolae from multiple sites on Walloon Lake, Higgins Lake,
      and Lake Leelanau, located in the northern region of the lower peninsula of
      Michigan. Snails were examined for infections using the light-box technique
      (exposure to bright fluorescent light). The prevalence of infected snails varied
      significantly among lakes within a year, between years in a lake, at a site from
      year to year, and at a site over a collecting season. Overall annual prevalence
      ranged from 0.54% (1999) to 1.32% (2001) on Walloon Lake, from 0.56% (2001) to
      1.06% (1998) on Higgins Lake, and 0.30% (2001) to 0.89% (2000) on Lake Leelanau.
      Generally, the peak in prevalence coincided in July on the lakes. Prevalence was
      found to increase with snail length in all lakes. A comparison of the light-box
      technique and crushing snails demonstrated that prevalence varied in magnitude by
      technique as much as 1.2 and 5.7 times.

PMID- 16629308
TI  - A quantitative approach to the experimental transmission success of Echinostoma
      friedi (Trematoda: Echinostomatidae) in rats.
AB  - Using a range of parameters, the ability of rats (Rattus norvegicus) to
      successfully transmit Echinostoma friedi to the next host was examined under
      experimental conditions. The concept of Experimental Transmission Success (TM),
      defined as the number of hosts that become successfully infected after exposure
      to a number of infective stages produced by a previous host per unit of
      inoculation at which this latter host was exposed, was introduced. Using data for
      the egg output and miracidium hatching and infectivity, the TM permits us to
      estimate the ability of a particular definitive host species to successfully
      transmit a parasite species. This concept may be also useful to compare the
      transmission fitness of a parasite in different definitive host species.
      Moreover, variations of the Experimental Transmission Success over the course of
      the infection were calculated by the use of the Weekly Experimental Transmission
      Success (TMW). Overall, considering the complete duration of the experiment, the
      TM of E. friedi using rats as definitive hosts was 0.68 infected
      snails/metacercaria. However, positive values of the TMW were only obtained from
      2 to 4 wk post-infection, with a maximum during the third wk post-infection. When
      comparing the TM values of E. friedi in rats with those calculated in hamsters on
      the basis of previously published data, E. friedi appears to be more appropriate
      to move through this portion of its life cycle when using hamsters (Mesocricetus
      auratus) as the final host than rats.

PMID- 16629309
TI  - A new species of Monocotyle taschenberg, 1878 (Monogenea: Monocotylidae) from
      Dasyatis guttata (Dasyatidae).
AB  - Monocotyle guttatae n. sp. is described from the gills of the ray Dasyatis
      guttata (Bloch and Schneider, 1801) (Dasyatidae) off the coast of Brazil The new
      species can be readily differentiated from the other species of the genus in
      having a male copulatory organ with 2 loops and an accessory piece, 5-7 sclerites
      on the marginal haptoral papillae, and the absence of accessory sclerites on the
      dorsal surface of the posterior body. The present record confirms the presence of
      the genus in the subtropical waters of South America.

PMID- 16629310
TI  - Ecomorphology of parasite attachment: experiments with feather lice.
AB  - The host specificity of some parasites can be reinforced by morphological
      specialization for attachment to mobile hosts. For example, ectoparasites with
      adaptations for attaching to hosts of a particular size might not be able to
      remain attached to larger or smaller hosts. This hypothesis is suggested by the
      positive correlation documented between the body sizes of many parasites and
      their hosts. We adopted an ecomorphological approach to test the attachment
      hypothesis. We tested the ability of host-specific feather lice (Phthiraptera:
      Ischnocera) to attach to 6 novel species of pigeons and doves that vary in size
      by nearly 2 orders of magnitude. Surprisingly, Rock Pigeon lice (Columbicola
      columbae) remained attached equally well to all 6 novel host species. We tested
      the relative importance of 3 factors that could facilitate louse attachment:
      whole-body insertion, tarsal claw use, and mandible use. Insertion, per se, was
      not necessary for attachment. However, insertion on coarse feathers of large
      hosts allowed lice to access feather barbules with their mandibles. Mandible use
      was a key component of attachment regardless of feather size. Attachment
      constraints do not appear to reinforce host specificity in this system.

PMID- 16629311
TI  - Molecular identification of Babesia parasites isolated from Ixodes ricinus ticks
      collected in northwestern Poland.
AB  - In the present study, PCR has been applied to detect and analyze DNA of Babesia
      spp. extracted from Ixodes ricinus ticks. Collection of I. ricinus was made in 6
      forested areas of Zachodniopomorskie Voivodship, Poland, during 2 seasonal peaks
      of tick activity, i.e., spring and autumn, 2001. In total, 1,328 I. ricinus were
      collected and processed for PCR with F34 and R323 primers. Babesia spp. was
      detected in 28 (2% of 1,328 tested) ticks; 26 were identified as B. divergens.
      The other 2 were identified as B. microti. PCR was conducted with 18S rRNA
      specific primers and sequencing was processed to precisely identify and compare
      these isolates with B. microti and B. divergens sequences from Europe, North
      America, and Asia obtained from the GenBank. Analysis revealed that sequences of
      B. microti from northwestern Poland are almost identical (99.94%) with those
      referred to as "Munich strain"; both form a clade different from other European
      strains, as well as those from Asia and North America (called B. microti, sensu
      stricto). An investigation performed with B. divergens sequences showed that the
      sequence from northwestern Poland is 99.94% homologous to an isolate from Ireland
      ("Purnel"), and differs in just a few nucleotides from other European sequences.
      Phylogenetic analysis revealed that the sequence of B divergens isolated from
      Polish ticks form a group that comprise 4 European sequences from Great Britain
      and Ireland and is, therefore, closely related to other European and North
      American B. divergnens sequences.

PMID- 16629312
TI  - Characterization of Toxoplasma gondii isolates in free-range chickens from
      Amazon, Brazil.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii in 50 free-range chickens (Gallus domesticus)
      from Amazon, Brazil, was determined. Antibodies to T. gondii were assayed by the
      modified agglutination test (MAT) and found in 33 (66%) chickens with titers of
      1:5 in 3, 1:10 in 2, 1:20 in 1, 1:40 in 1, 1:80 in 2, 1:160 in 5, 1:200 in 9,
      1:400 in 5, 1:800 in 2, 1:1,600 in 2, and 1:3,200 or higher in 1. Hearts and
      brains of 33 seropositive chickens were bioassayed individually in mice. Tissues
      from 17 seronegative chickens were pooled and fed to 2 T. gondii-free cats. Feces
      of cats were examined for oocysts, but none was found. Toxoplasma gondii was
      isolated from 24 chickens with MAT titers of 1:5 or higher. Genotyping of these
      24 T. gondii isolates by polymorphisms at the SAG2 locus indicated that 14 were
      type I, and 10 were type III; the absence of type II strains from Brazil was
      confirmed. Fifty percent of the infected mice died of toxoplasmosis, irrespective
      of the genotype.

PMID- 16629313
TI  - Concomitant immunity in a rodent model of filariasis: the infection of Meriones
      unguiculatus with Acanthocheilonema viteae.
AB  - In an attempt to study the occurrence of concomitant immunity in filarial
      infections, jirds (Meriones unguiculatus) were experimentally infected with
      Acanthocheilonema viteae, and patent animals were superinfected with a defined
      dose of A. viteae stage 3 larvae (L3). Infected animals harbored significantly
      less worms deriving from the superinfection than the control group (P < 0.05,
      56.2%, and 63.4% protection), as shown by analysis of female worms 6 wk after
      superinfection on the basis of their developmental status and their length. This
      protection was not due to contact with L3 antigens because a significant
      reduction of worm burdens deriving of a superinfection was also observed after
      subcutaneous implantation of a single female worm (P < 0.05, 40.2% and 64.9%
      protection). The induced protective responses target L3 and restrict their
      migration because an established infection resulted in a reduction of L3 recovery
      (95.6% and 94.3%, P < 0.001) from tissues of jirds at day 5 after superinfection.
      Other data show that L3 from a superinfection are trapped within eosinophil-rich
      granulomas, which is likely to create unfavorable conditions for the worms and to
      lead to later death. Taken together, established A. viteae-infections partially
      protect hosts against homologous superinfection by an immune-mediated mechanism
      and, thus, regulate the population density of the parasites within the host by
      concomitant immunity.

PMID- 16629314
TI  - Tissue migration capability of larval and adult Brugia pahangi.
AB  - Infection with mosquito-born filarial nematodes occurs when hosts are bitten by a
      vector carrying the infective third stage larvae (L3) of the parasites. These
      larvae, deposited on the skin by the feeding mosquito, are presumed to enter the
      skin via the vector-induced puncture wound. Larvae of Brugia spp. must then
      migrate from the entry site, penetrate various skin layers, and locate a
      lymphatic vessel that leads to their lymphatic predilection site. We have
      recently established an intradermal (ID) infection model using B. pahangi and the
      Mongolian gerbil, allowing us to investigate the migratory capability ofB.
      pahangi. Larval and adult parasites recovered from the peritoneal cavities of
      gerbils were capable of establishing an infection following ID (larvae) or
      subcutaneous (adult) injection. Third and fourth stage larvae both migrated away
      from the injection site within hours, although data suggest they localize to
      different lymphatic tissues at 3 days postinfection (DPI). Immature adult (28
      day) B. pahangi also migrated away from their SC inoculation site within 7 DPI.
      Mature (45 day) adult B. pahangi displayed little migration away from the SC
      infection site, suggesting tissue migration may be limited to developing stages
      of the parasite.

PMID- 16629315
TI  - The myxozoan fauna of Fundulus diaphanus (Cyprinodontidae) from freshwater
      localities in eastern North America: prevalence, community structure, and
      geographic distribution.
AB  - Membership and richness of infracommunities and component communities of myxozoan
      fauna of the banded killifish (Fundulus diaphanus) from freshwater localities in
      Ontario, Quebec, New York State, New Brunswick, Nova Scotia, and Maryland were
      studied. Five species of parasites were found: Myxobolus diaphanus (Fantham,
      Porter, and Richardson, 1940) (connective tissue throughout the body and head),
      Myxobolus funduli (Kudo, 1918) (interlamellar), Myxobolus neurophilus (Guilford,
      1963) (optic tectum of the brain), Myxobolus sp. (connective tissue, typically
      adjacent to vertebrae), and Sphaerospora sp. (kidney tubules). The most abundant
      species locally and regionally was M. diaphanus, occurring at prevalences of 14.2
      to 93.3% at 6 of 9 localities. Myxobolus funduli and Myxobolus sp. were at 3 and
      2 localities respectively, while M. neurophilus and Sphaerospora each occurred at
      single localities. Four of the 5 myxozoans appear to be specific to fundulids,
      the exception being M. neurophilus, which is typically a parasite of Perca
      flavescens. Mean infracommunity richness was 0-1.2. Component community richness
      was 0-3 species. The fauna is similar in composition to that described from the
      spottail shiner (Notropis hudsonius) in the Great Lakes in being dominated by
      histozoic myxobolids and in having maximum prevalence at any single locality
      correlate positively with geographical distribution. Moreover, mean
      infracommunity richness was correlated with percentage of hosts infected with any
      species at a locality, and maximum infracommunity richness was correlated with
      component community richness. Probably because fewer species of myxozoans of
      fundulids occur in the regional pool, myxozoan communities encountered in the
      present study are generally less rich than those described from N. hudsonius. It
      appears that dispersal of relatively resilient myxospores through such a
      mechanism as piscivory effectively distributes these parasites over the
      landscape, while the more delicate actinospores serve to ensure colonization by
      amplifying species' prevalence at a specific locality and thereby contributing to
      initial establishment. As such, these types of myxozoans, though they are
      autogenic, having their entire life cycle normally completed within the aquatic
      environment, behave more like allogenic parasites that rely on birds and mammals
      as definitive hosts.

PMID- 16629316
TI  - Cryptosporidium parvum: treatment effects and the rate of decline in oocyst
      infectivity.
AB  - Cryptosporidium parvum has become the focus of numerous studies on waterborne
      disease and transmission in response to outbreaks endangering populations
      worldwide. The Foci Detection Method-Most Probable Number Assay (FDM-MPN) is an
      in vitro cell culture method that has been developed and used to determine the
      quantity of infectious C. parvum oocysts. This research evaluated 2 vendor's
      producing oocysts, Sterling Parasitology Laboratory (SPL) and Pleasant Hill Farms
      (PHF) (now known as Bunch Grass Farms as of 12/03), classified as young (<30
      days) and aged (>165 days), for comparison of treatments (bleach, antibiotic, no
      treatment) before cell culture, as well as an age study, to determine any lot-to
      lot differences and vendor differences regarding the rate of decline in
      infectivity. Bleach treatment (0.525%) appeared to be the optimum method for the
      FDM-MPN with regards to maximum infectivity, efficient disinfection, with no
      visible antagonistic affects on the C. parvum oocysts. The age study revealed
      that lot-to-lot variability within each vendor stayed within 1 log10 difference,
      while the rates of decline in infectivity measured until 107 and 120 days of age
      when stored at 4 C for SPL and PHF were -0.016 and -0.014 log10 infectious
      oocysts/day, respectively. These results provide insight regarding C. parvum
      oocyst viability in a fecal population, as well as useful knowledge for further
      methods development.

PMID- 16629317
TI  - Identification and characterization of the threadworm, Strongyloides procyonis,
      from feral raccoons (Procyon lotor) in Japan.
AB  - Strongyloides procyonis Little, 1966 was detected about 45 years ago in raccoons
      (Procyon lotor) of southern Louisiana, U.S.A., and was demonstrated
      experimentally to cause creeping eruption and a short-lived intestinal infection
      in a healthy human volunteer. After its description and demonstration of its
      pathogenicity in humans, S. procyonis has not been found in raccoons in North
      America despite repeated surveys. During a survey on feral raccoons in Japan, S.
      procyonis parasitic females were identified in 66 (28.3%) of 233 raccoons
      collected between May 2004 and January 2005. The number of parasitic females
      recovered from individual raccoons was 1-197 (geomean, 3.2). Both the
      morphological features and the nucleotide sequences of the small and large
      subunit ribosomal RNA genes (SSU/LSU rDNA) of S. procyonis closely resembled
      those of zoonotic Strongyloides stercoralis. The sequences of internal
      transcribed spacer (ITS)1 and 28S rDNA could differentiate clearly these 2
      species. Awareness of S. procyonis in raccoons in North America and other places
      worldwide where raccoons are introduced and naturalized is important to assess
      the epidemiological significance of this potentially zoonotic helminth species.

PMID- 16629318
TI  - Eimeria species from the European pond turtle, Emys orbicularis (Reptilia:
      Testudines), in Galicia (NW Spain), with description of two new species.
AB  - Parasitological examination of feces from 44 Emys orbicularis from Galicia (NW
      Spain) revealed the presence of 2 new eimerian species, Eimeria gallaeciaensis
      sp. n. and E. emydis sp. n., as well as E. mitraria (Laveran and Mesnil, 1902)
      Doflein, 1909. Oocysts of E. gallaeciaensis n. sp. were found in 20 of 44 (45.4%)
      turtles and are subspherical to lightly ovoid-ellipsoid, 19.3 x 16.0 (17-22 x 15
      18) microm, shape index 1.2 (1.1-1.3), with a smooth, single-layered wall.
      Micropyle and polar granule are absent, but an oocyst residuum is present.
      Sporocysts are ellipsoid, 9.7 x 5.1 (9-10 x 5-6) microm, shape index 1.9 (1.7
      2.0), each with a sporocyst residuum and a conical Stieda body usually bearing 1
      4 short and thin projections. Oocysts of E. emydis n. sp. were found in the feces
      of 5 of 44 (11.4%) turtles and are ovoid, rarely pear-shaped, 22.6 x 17.0 (20-25
      x 15.5-18) microm, shape index 1.3 (1.2-1.5), with a smooth, single-layered wall
      with a slight thinning at the pointed end. Micropyle and polar granule are
      absent, and an oocyst residuum is present. Sporocysts are ellipsoid, 11.4 x 6.0
      (9-13 x 5-7) microm, shape index 1.9 (1.6-2.2), each with sporocyst residuum and
      a prominent Stieda body bearing 3-5 club-shaped projections. In addition to the
      new species described, this is the first report of E. mitraria parasitizing E.
      orbicularis.

PMID- 16629319
TI  - Karyakartia egyptensis n. sp. (Digenea: Lepocreadiidae) from the Jarbua terapon,
      Terapon jarbua (Forsskal) (Perciformes: Terapontidae), from the Red Sea and
      emendation of Karyakartia.
AB  - Karyakartia egyptensis n. sp. (Digenea: Lepocreadiidae: Lepocreadiinae) is
      described from the intestine of the Jarbua terapon, Terapon jarbua (Forsskal),
      collected from the Red Sea off the coast of Hurghada, Egypt. Karyakartia
      egyptensis n. sp. differs from K. pambanense in that the former species possesses
      larger spiniform structures around the perimeter of the mouth (48-54 microm as
      compared with 25-30 microm), a uroproct rather than ceca that end blindly or form
      a cyclocoel, and a somewhat smaller egg (60-68 microm as compared with 70-73
      microm).

PMID- 16629320
TI  - An approach to revealing blood fluke life cycles, taxonomy, and diversity:
      provision of key reference data including DNA sequence from single life cycle
      stages.
AB  - Revealing diversity among extant blood flukes, and the patterns of relationships
      among them, has been hindered by the difficulty of determining if specimens
      described from different life cycle stages, hosts, geographic localities, and
      times represent the same or different species. Persistent collection of all
      available life cycle stages and provision of exact collection localities, host
      identification, reference DNA sequences for the parasite, and voucher specimens
      eventually will provide the framework needed to piece together individual life
      cycles and facilitate reconciliation with classical taxonomic descriptions,
      including those based on single life cycle stages. It also provides a means to
      document unique or rare species that might only ever be recovered from a single
      life cycle stage. With an emphasis on the value of new information from field
      collections of any available life cycle stages, here we provide data for several
      blood fluke cercariae from freshwater snails from Kenya, Uganda, and Australia.
      Similar data are provided for adult worms of Macrobilharzia macrobilharzia and
      miracidia of Bivitellobilharzia nairi. Some schistosome and sanguinicolid
      cercariae that we recovered have peculiar morphological features, and our
      phylogenetic analyses (18S and 28S rDNA and mtDNA CO1) suggest that 2 of the new
      schistosome specimens likely represent previously unknown lineages. Our results
      also provide new insights into 2 of the 4 remaining schistosome genera yet to be
      extensively characterized with respect to their position in molecular
      phylogenies, Macrobilharzia and Bivitellobilharzia. The accessibility of each
      life cycle stage is likely to vary dramatically from one parasite species to the
      next, and our examples validate the potential usefulness of information gleaned
      from even one such stage, whatever it might be.

PMID- 16629321
TI  - A new species of Malmiana (Oligochaeta: Hirudinida: Piscicolidae) from tidepool
      fishes in northern California.
AB  - Malmiana buthi n. sp. is described from the body and fins of the fluffy sculpin,
      Oligocottus snyderi, the tidepool sculpin, Oligocottus maculosus, and the woolly
      sculpin, Clinocottus analis, collected from tidepools at Horseshoe Cove on the
      Bodega Marine Reserve in Sonoma County, California. Prevalence of the leech was
      32.6% on live-caught O. snyderi; mean intensity on O. snyderi was 3.3 leeches per
      fish, with a range from 1 to 7. The leech is not known to exceed 8 mm total
      length. The body is smooth, lacking papillae, tubercles, or pulsatile vesicles.
      Two pairs of crescentiform eyes are present on the oral sucker, and 1 pair of
      punctiform eyes occurs on the second annulus of the trachelosome. The caudal
      sucker has 14 small punctiform ocelli spaced evenly around the margin. The last 9
      segments of the urosome have pairs of large punctiform ocelli both dorsally and
      ventrally. Body and caudal sucker pigmentation is uniformly reddish brown
      dorsally and ventrally with segental, lateral, unpigmented areas on both the
      urosome and trachelosome; pigmentation on the oral sucker is in the form of a
      cross. There are 5 pairs of testisacs; accessory gland cells on the atrial cornua
      and vector tissue are absent.

PMID- 16629322
TI  - New molecular data on mammalian Hepatozoon species (Apicomplexa: Adeleorina) from
      Brazil and Spain.
AB  - Molecular techniques were used to examine the phylogenetic relationships among
      Hepatozoon species isolated from 13 foxes and 15 opossums from Brazil, and from
      15 dogs, 20 foxes, 45 rodents, and 330 domestic cats from Spain. Hemogregarine
      infection was confirmed by amplification of the 18S rRNA gene and later
      sequencing. No hemogregarine infections were found in opossums. The prevalence of
      Hepatozoon in canids ranged from 26.6% (symptomatic domestic dogs) to 90%
      (Spanish foxes). Four different H. canis genotypes were detected, as well as an
      H. americanum-related protozoan (97% identical to the USA strain). Two Spanish
      cats were parasitized by a Hepatozoon species (0.6% prevalence) that showed 96%
      sequence identity to H. canis. DNA amplification assays performed on Spanish
      rodents showed 2 bank voles (Clethrionomys glareolus) to be infected by a
      Hepatozoon species (4.44% prevalence) with 95% sequence identity to Hepatozoon
      sp. from cats. Phylogenetic analysis showed Hepatozoon to be a monophyletic
      genus, in which species from carnivorous mammals (Hepatozoon sp. from cats, H.
      americanum and H. canis) appear as a sister lineage of that of lower vertebrates
      and rodents. This association suggests that H. americanum evolved in ticks and
      carnivores (either canids, or felids, or both) rather than in other ectoparasites
      and other types of mammal.

PMID- 16629323
TI  - A new species of Trichuris (Nematoda: Trichuridae) from Phyllotini rodents in
      Argentina.
AB  - A new species of Trichuris is described. Trichuris pardinasi n. sp. was recovered
      from Phyllotis xanthopygus Waterhouse (Rodentia: Muridae: Phyllotini) in Sierra
      de la Ventana, Buenos Aires Province, and Pampa de Achala, Cordoba Province
      (Argentina). This is the first record of Trichuris parasitizing Phyllotini
      rodents. The new species can be differentiated from the other 10 species
      parasitizing rodents from South America by the absence of the spicular tube,
      spicular sheath with spines uniformly distributed, the length of spicule, the J
      shaped proximal cloacal tube, and the nonprotrusive vulva. Also, a description of
      the bacillary band is provided. The present and the future findings of shared
      parasite fauna from both populations of P. xanthopygus in these disjunct areas
      will support the hypothesis of a continuous distribution of this host species at
      a past time.

PMID- 16629324
TI  - Five new species of Acanthobothrium (Tetraphyllidea: Onchobothriidae) from the
      freshwater stingray Himantura chaophraya (Batoidea: Dasyatidae) in Malaysian
      Borneo.
AB  - Five new species of Acanthobothrium (Tetraphyllidea: Onchobothriidae) are
      described from the spiral intestine of the Freshwater whipray, Himantura
      chaophraya, in the Kinabatangan River in Malaysian Borneo. Based on criteria set
      forth in a previous categorization scheme for species of Acanthobothrium, these
      consist of 3 Category 1 species, Acanthobothrium asnihae n. sp., Acanthobothrium
      saliki n. sp., and Acanthobothrium zainali n. sp.; a Category 8 species,
      Acanthobothrium etini n. sp.; and a Category 2 species, Acanthobothrium masnihae
      n. sp.. Acanthobothrium asnihae n. sp. differs from all Category 1 species in its
      possession of a horizontal band of weak musculature that divides the posterior
      loculus in half. Among Category 1 species, A. saliki n. sp. differs from all but
      Acanthobothrium southwelli in its possession of postovarian testes. It differs
      from A. southwelli in its possession of fewer testes and a greater number of
      proglottids. Acanthobothrium zainali n. sp. differs from the 25 other Category 1
      species in a combination of overall size, muscular pad and hook shape,
      arrangement and number of testes, ovary configuration in cross section, position
      of ovarian isthmus, and genital pore position. Acanthobothrium etini n. sp. is
      distinguished from all 5 other Category 8 species in its lack of testes from the
      proglottid antiporal and postporal regions and in testis number. Acanthobothrium
      masnihae n. sp. differs from the 35 other Category 2 species in its possession of
      fewer testes, postporal testes, or a greater number of proglottids. A key to
      Acanthobothrium species parasitizing H. chayophraya is presented. This represents
      the first report of Acanthobothrium from freshwater stingrays belonging to a
      family other than the Potamotrygonidae.

PMID- 16629325
TI  - Australicola pectinatus n. gen. and n. sp. (Cestoda: Pseudophyllidea) from the
      deep-sea fish Beryx splendens from Tasmania.
AB  - Australicola pectinatus n. gen., n. sp. (Pseudophyllidea: Triaenophoridae) is
      proposed to accommodate a new cestode from a deep-sea fish, the splendid
      alfonsino, Beryx splendens Lowe, 1834 (Beryciformes: Berycidae), from the Pacific
      coast of Tasmania. The new genus is placed in the Triaenophoridae, because it
      possesses a ventral uterine pore, marginal genital pore, and follicular
      vitellarium. Australicola is characterized by possessing a massive strobila with
      very short and wide, markedly craspedote proglottids; vitelline follicles forming
      a transverse equatorial band; a very deep and narrow genital atrium; a wide,
      convoluted vaginal canal; and unoperculate eggs. Australicola most closely
      resembles Eubothrium Nybelin, 1922 and Probothriocephalus Campbell, 1979 in
      having an unarmed scolex, an unarmed cirrus, the vagina anterior to the cirrus
      sac, and cortical vitellaria. It differs from these 2 genera, in addition to the
      characteristics listed above, in possessing a dendritic rather than an entire
      ovary. Australicola pectinatus n. sp. is the third cestode described from B.
      splendens.

PMID- 16629326
TI  - A new species of Procamallanus (Nematoda: Camallanidae) from Pacific eels
      (Anguilla spp.).
AB  - A new species of parasitic nematode, Procamallanus (Procamallanus) pacificus n.
      sp., is described from the stomach of the Pacific shortfinned eel, Anguilla
      obscura (type host), and from the speckled longfin eel, Anguilla reinhardtii,
      from northern New Caledonia (Melanesia, South Pacific); from Anguilla sp. (cf.
      obscura) from the Fiji Islands (Melanesia, South Pacific); and from the giant
      mottled eel Anguilla marmorata from Futuna Island (Wallis and Futuna Islands,
      Polynesia). Although a total of 450 nematodes were collected, all specimens were
      females; this suggests either an extremely rare occurrence of males or
      parthenogenetic reproduction in this species. Procamallanus pacificus differs
      markedly from all congeners from fish hosts in possessing a greater number (4-9)
      of caudal mucrons in the female and by other morphological features. This
      parasite might become a serious pathogen of cultured eels in the region of the
      South Pacific. Batrachocamallanus Jackson and Tinsley, 1995 is considered a
      junior synonym of Procamallanus Baylis, 1923, to which 2 species are transferred
      as Procamallanus occidentalis (Jackson and Tinsley, 1995) n. comb. and
      Procamallanus siluranae (Jackson and Tinsley, 1995) n. comb. One third-stage
      larva of Procamallanus (Spirocamallanus) sp. was also recorded from Anguilla sp.
      (cf. obscura) from the Fiji Islands.

PMID- 16629327
TI  - Redescription of Alinema amazonicum (Travassos, 1960) n. comb., a philometrid
      nematode with unusual morphology.
AB  - Nematodes (1 male and numerous females) of the Philometridae were collected from
      the mesentery of 2 species of pimelodid catfishes, Calophysus macropterus and
      Perrunichthys perruno, from the Amazon River basin (fishmarket in Iquitos, Loreto
      District) in Peru. A detailed study of their morphology (including scanning
      electron microscopy) and a reexamination of the type and voucher specimens of
      Philometra amazonica Travassos, 1960, from Brazilian catfishes confirmed that
      they belong to this species and that Philometra (Alinema) alii Rasheed, 1963 is
      its junior synonym. Because of some marked morphological peculiarities of this
      species (presence of minute peribuccal sclerotized formations, a functional
      vagina and vulva in gravid female, and structure of the male tail), the validity
      of an independent genus, Alinema Rasheed, 1963, is confirmed, to which this
      species is transferred as Alinema amazonicum (Travassos, 1960) n. comb. This is
      the first record of this parasite from Peru, and P. perruno represents its new
      host record.

PMID- 16629328
TI  - Two new species of Paraorygmatobothrium (Cestoda: Tetraphyllidea) from weasel
      sharks (Carcharhiniformes: Hemigaleidae) of Australia and Borneo.
AB  - Two new species of Paraorygmatobothrium Ruhnke, 1994, P. janineae n. sp. and P.
      kirstenae n. sp., are described from the spiral intestine of 2 shark species of
      the Family Hemigaleidae: Hemigaleus microstoma and Hemipristis elongata. The 2
      new cestode species differ from other members of Paraorygmatobothrium in
      vitelline follicle distribution and possession of a cephalic peduncle. The 2 new
      species differ from 1 another in total length, maximum width, scolex size, number
      of proglottids per strobila, and number of testes per proglottid. The generic
      diagnosis of Paraorygmatobothrium is emended to include the new species. The
      results of this study extend the distribution of Paraorygmatobothrium to include
      the carcharhinid shark family Hemigaleidae.

PMID- 16629329
TI  - A new species of Cucullanus (Nematoda: Cucullanidae) parasitizing Conger
      orbignianus (Pisces: Congridae) from Argentinean waters.
AB  - In total, 17 specimens of Conger orbignianus Valenciennes, 1847 from waters off
      Mar del Plata, Argentina (38 degrees 08'S, 57 degrees 32'W) were examined for
      parasitic nematodes. A new nematode species, Cucullanus pedroi n. sp., is
      described (prevalence 76.5%, x intensity +/- SD = 3.8 +/- 2.7). The new species
      closely resembles some species parasitizing other anguilliform fishes; however,
      it can be distinguished from most of its congeners by the distribution pattern of
      caudal papillae (particularly fourth and eight pairs) and phasmids. Those
      congeners with similar pattern of papillae differ from the new species by the
      length of the spicules and gubernaculum and by the position of the excretory pore
      and deirids.

PMID- 16629330
TI  - Genetic relationships among Anisakis species (Nematoda: Anisakidae) inferred from
      mitochondrial cox2 sequences, and comparison with allozyme data.
AB  - The genetic relationships among 9 taxa of Anisakis Dujardin, 1845 (A. simplex
      (sensu stricto), A. pegreffii, A. simplex C., A. typica, A. ziphidarum, A.
      physeteris, A. brevispiculata, A. paggiae, and Anisakis sp.) were inferred from
      sequence analysis (629 bp) of the mitochondrial cox2 gene. Genetic divergence
      among the considered taxa, estimated by p-distance, ranged from p = 0.055,
      between sibling species of the A. simplex complex, to p = 0.12, between
      morphologically differentiated species, i.e., A. ziphidarum and A. typica. The
      highest level was detected when comparing A. physeteris, A. brevispiculata, and
      A. paggiae versus A. simplex complex (on average p = 0.13) or versus A. typica
      (on average p = 0.14). Sequence data from the newly identified Anisakis sp.
      poorly aligned with other Anisakis species but was most similar to A. ziphidarum
      (p = 0.08). Phylogenetic analyses based upon Parsimony and Bayesian Inference, as
      well as phenetic analysis based upon Neighbor-Joining p-distance values,
      generated similar tree topologies, each well supported at major nodes. All
      analyses delineated two main claides, the first encompassing A. physeteris, A.
      brevispiculata, and A. paggiae as a sister group to all the remaining species,
      and the second comprising the species of the A. simplex complex (A. simplex
      (s.s.), A. pegreffii and A. simplex C), A. typica, A. ziphidarum, and Anisakis
      sp. In general, mtDNA-based tree topologies showed high congruence with those
      generated from nuclear data sets (19 enzyme-loci) and with morphological data
      delineating adult and larval stages of the Anisakis spp.; however, precise
      positioning of A. typica and A. ziphidarum remain poorly resolved, though they
      consistently clustered in the same clade as Anisakis sp. and the A. simplex
      complex. Comparison of anisakid data with those currently available for their
      cetacean-definitive hosts suggests parallelism between host and parasite
      phylogenetic tree topologies.

PMID- 16629331
TI  - A new species of Neohaematotrephus (Digenea: Echinostomiformes: Cyclocoelidae) in
      the spotted-sandpiper Actitis macularia (Charadriiformes: Scolopacidae) from
      Venezuela.
AB  - Fischthal and Nasir (1974) reported Neohaematotrephus brasilianum (as Cyclocoelum
      brasilianum) in the spotted-sandpiper Actitis macularia from Venezuela. Three
      voucher specimens from that report, deposited in the United States National
      Parasite Collection, however, differ from N. brasilianum by having the cirrus sac
      on the sinistral side of the body, which resembles N. facioi, N. arayae, and N.
      gendrei. The new species is similar to N. brasilianum by having vitelline
      follicles extending well anterior to the intestinal bifurcation and by having a
      short and laterally displaced cirrus sac whose posterior end does not reach the
      intestinal bifurcation, whereas all other members of Neohaematotrephus have a
      cirrus sac that is medially oriented. Neohaematotrephus gendrei and N. facioi
      have cirrus sacs that extend to the level of the intestinal bifurcation, and N.
      arayae has a cirrus sac that extends well posterior to the posterior margin of
      the ceca. By having the ovary on the sinistral side of the body, the new species
      is similar to N. brasilianum, N. gendrei, and N. arayae but differs from N.
      facioi, in which the ovary is dextral.

PMID- 16629332
TI  - Iron chelators: correlation between effects on Plasmodium spp. and immune
      functions.
AB  - Iron chelating agents, which permeate through erythrocytic and parasite
      membranes, are effective against Plasmodium falciparum in vitro. However, the
      protective effect in humans is transient. We examined the antiplasmodial capacity
      of several iron chelators in vitro and in vivo. The chelators 3/3hb/2m and
      3/2hb/b (together, MoB) were more effective against P. falciparum in vitro than
      desferrioxamine (DFO) and Salicylaldehyde isonicotinoyl hydrazone (SIH)
      (together, DoS). Despite similar pharmacokinetics of all iron chelators, mice
      infected with Plasmodium vinckei and treated with MoB succumbed to malaria,
      whereas DoS-treated mice survived. However, even in the surviving mice, peak
      parasitemias were above 30%. These results indicate that the direct effects of
      the drugs on the parasites were not responsible alone for the complete recovery
      of the mice. We suggest that the recovery is related to differential effects of
      the drugs on various immune functions. We concentrated on the effect of the iron
      chelators on B cell and T cell proliferation and on allogeneic stimulation (MLR),
      interleukin-10 (IL-10), gamma-interferon (gamma-IFN), tumor necrosis factor-alpha
      (TNF-alpha), and radical production. All the iron chelators examined inhibited
      the in vitro proliferation of B cells and T cells, and MLR. This may explain why
      iron chelators are only slightly efficient in treating human malaria. However,
      the inhibitory effects of MoB on B cell and T cell proliferation and on MLR were
      more pronounced than those of DoS. In addition, the release of free radicals by
      effector cells was inhibited to a greater extent by MoB than by DoS. These
      results may explain why MoB, which was more efficient in vitro, was not effective
      in vivo. The DoS effects on the in vitro secretion of cytokines correlate with
      their in vivo effect; there was a decrease of IL-10 and a parallel increase in
      gamma-IFN and TNF-alpha production by human mononuclear cells. MoB, which could
      not rescue the animals from malaria, did not affect IL-10 and TNF-alpha, but
      reduced gamma-IFN levels. Identical results were obtained when using monocytes
      instead of mononuclear cells (except for gamma-IFN, which is not produced by
      monocytes). Our results indicate that an iron chelator, or any antiparasitic drug
      that kills the parasites in vitro, should also be selected for further evaluation
      on the basis of its reaction with immune components; it should not interfere with
      crucial protective immunological processes, but it may still alleviate
      parasitemia by positive immune modulation.

PMID- 16629333
TI  - Serological survey with PCR validation for canine visceral leishmaniasis in
      northern Palestine.
AB  - Leishmania infantum is the causative agent of human and canine visceral
      leishmaniasis (CVL) in the Mediterranean region. A seroprevalence study for CVL
      was conducted in northern Palestine. Domestic dogs (n = 148) were screened for
      antileishmanial antibodies by enzyme-linked immunosorbent assay (ELISA). Ten dogs
      (6.8%) were seropositive. Promastigotes were isolated from one seropositive dog
      and identified as L. infantum by excreted factor (EF) serotyping, isozyme
      electrophoresis, and polymerase chain reaction (PCR). In addition to the ELISA,
      the internal transcribed spacer 1 (ITS1)-, modified ITS1 (mITS1)-, and
      kinetoplast DNA (kDNA)-PCRs were used to validate this technique as a diagnostic
      tool for CVL using blood; each assay was performed on 60 blood samples. kDNA-PCR
      (13/60 positives, 21.7%) was the most sensitive of the assays examined followed
      by mITS1-PCR (9/60, 15.0%), ELISA (5/60, 8.3%), and ITS1-PCR (3/60, 5%). However,
      ITS1-PCR and mITS1-PCR were also capable of identifying the parasite species and
      indicated they belong to L. infantum. In view of its higher sensitivity, kDNA-PCR
      is recommended for the routine diagnosis of CVL.

PMID- 16629334
TI  - Characterization of Toxoplasma gondii isolates in free-range chickens from
      Portugal.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii in 225 free-range chickens (Gallus
      domesticus) from Portugal was determined. Antibodies to T. gondii were assayed by
      the modified agglutination test (MAT) and found in 61 chickens with titers of 1:5
      in 8, 1:10 in 6, 1:20 in 3, 1:40 in 23, 1:80 in 5, 1:160 in 4, 1:320 in 8, and
      1:640 or higher in 4. Hearts, leg muscles, and brains of 15 seropositive (MAT
      1:10 or higher) chickens were bioassayed individually in mice. Tissue from 38
      chickens with titers of 1:5 or less were pooled and fed to a T. gondii-free cat.
      Feces of the cat were examined for oocysts, but none was found. Toxoplasma gondii
      was isolated from 16 of 19 chickens with MAT titers of 1:10 or higher. Genotyping
      of 12 of these 16 isolates with polymorphisms at the SAG2 locus indicated that 4
      were type III, and 8 were type II. None of the isolates was lethal for mice.
      Phenotypically, T. gondii isolates from chickens from Portugal were different
      from those of T. gondii isolates from chickens from Brazil.

PMID- 16629335
TI  - Helminth assemblages of the turtle Emydura macquarii (Pleurodira: Chelidae)
      Queensland, Australia.
AB  - The helminth fauna of 76 Emydura macquarii from 3 river systems in central and
      northern Queensland was examined. Eleven species were found, including 2
      nematodes, 6 trematodes, 1 aspidogastrean, 1 cestode, and 1 monogenean. Analysis
      of helminth diversity showed that the Fitzroy and Ross River turtles had
      communities of comparable diversity, but the helminth communities in Proserpine
      River turtles were much less diverse. The helminth communities in all localities
      were dominated by trematodes. Polystomoides australiensis was the most prevalent,
      being found in 60% of the Ross River turtles, 57% of the Fitzroy River turtles,
      and 46% of the Proserpine River turtles. Notopronocephalus peekayi was the most
      abundant species, with mean abundances of 5.9 in the Ross River turtles and 9.8
      in the Fitzroy River turtles. Species richness, Simpson's Reciprocal Index, was
      highest, 4.68, for the Ross River helminth community, Sorensen's Qualitative
      Index showed 95% similarity between the Ross River and Fitzroy River communities,
      although Sorensen's Quantitative Index indicated only 35% similarity between the
      2 sites. Host feeding patterns are likely the most important factor affecting
      species richness of the helminth infracommunities, as the majority of helminth
      species are transmitted by food-web interactions involving intermediate hosts.

PMID- 16629336
TI  - Histomorphological study of the preputial and clitoral glands in BALB/c mice with
      experimental Taenia crassiceps infections.
AB  - Male preputial and female clitoral glands of mice undergo development that
      depends on the level of hormones in the animal. Experimental infection with
      Taenia crassiceps cysticerci results in significant physiological modifications
      in the host. Here, we investigated the histomorphological alterations induced by
      the parasite in these pheromonal glands. Preputial and clitoral glands were
      recovered from mice at 15, 35, 50, and 70 days postinfection (DPI). The glands
      were examined macroscopically and microscopically after histological preparation.
      Male preputial glands show a marked atrophy 35 days after infection. This atrophy
      is the result of a disorganization of the acinus tissue structure. During the
      course of infection, the basal, intermediate, and mature acinar cell layers are
      reduced, and finally, at 70 DPI, the gland includes only the duct system and
      fibrotic structures. In contrast, females are not affected by the infection
      because no modifications were observed in the morphology or histology of the
      clitoral glands. A probable cause for such a divergence between infected male and
      female mice might be related to a sex steroid imbalance as described during T.
      crassiceps infection.

PMID- 16629337
TI  - Influence of drying time on nematode eggs in scats of scincid lizard Egernia
      stokesii.
AB  - Two pharyngodonid nematode species, Pharyngodon tiliquae and Thelandros
      trachysauri, infect the Australian lizard Egernia stokesii (gidgee skink) in
      populations from South Australia. Eggs are detected in lizard scats that are
      deposited in piles outside the rock crevice refuges that the lizards occupy. Eggs
      were isolated by salt flotation from fresh scats and from scats that had been
      dried in simulated field conditions for 7, 14, 21, and 28 days. Egg counts
      decreased with drying time for both nematode species, but T. trachysauri eggs
      were still detected after 28 days of drying, whereas P. tiliquae eggs were rarely
      detected after 14 days. These results suggest that egg counts can be used to
      infer host infection status only from relatively fresh scats and that eggs of the
      2 species persist in a state where they can be detected by standard flotation
      techniques, for different times.

PMID- 16629338
TI  - Effects of high-pressure processing on Toxoplasma gondii tissue cysts in ground
      pork.
AB  - Ingestion of Toxoplasma gondii tissue cysts can result in severe disease in
      immunocompromised individuals and pregnant women. Treatment of meat and meat
      products to eliminate viable T. gondii tissue cysts would provide a means to
      protect consumers. In this study, we examined the effects of high-pressure
      processing (HPP) on ground pork containing viable tissue cysts of the VEG strain
      of T. gondii. Ground pork containing tissue cysts was exposed to 400, 300, 200,
      100, or 0 MPa treatment for 30, 60, or 90 sec in a commercial HPP unit. The HPP
      treated ground pork was subjected to acid-pepsin digestion and bioassayed in
      mice. The results of the mouse bioassay revealed that none of the mice inoculated
      with tissue cysts exposed to 400 or 300 MPa became infected, whereas all mice
      inoculated with tissue cysts exposed to 200, 100, or 0 MPa became infected with
      T. gondii regardless of exposure time. Results indicate that HPP treatment of
      ground pork with 300 MPa of pressure will render tissue cysts of T. gondii
      nonviable and make pork safe for human consumption.

PMID- 16629339
TI  - Use of Trichomonas vaginalis clinical isolates to evaluate correlation of gene
      expression and metronidazole resistance.
AB  - We investigated whether variations in gene expression of enzymes associated with
      anaerobic resistance of laboratory-derived strains of Trichomonas vaginalis could
      be detected in a group of 28 clinical isolates with variations in metronidazole
      sensitivity. We compared isolates by real-time PCR because this method allows for
      highly sensitive quantification of mRNA and for evaluation of several genes
      simultaneously. We found that PFOR gene A mRNA levels were highly correlated with
      PFOR gene B levels, as well as the D subunit of malic enzyme and ferrodoxin.
      Ferrodoxin mRNA expression was also significantly correlated with that of malic
      enzyme and hydrogenase. However, when we evaluated relationships between these
      enzymes and resistance to metronidazole, we found no significant correlations
      between aerobic or anaerobic in vitro sensitivity to drug and mRNA levels of any
      of the enzymes tested. Similarly, using a Student's t-test, no significant
      differences in enzyme mRNA levels were observed between isolates separated by
      metronidazole resistance or susceptibility. The lack of correlation between gene
      expression and resistance or susceptibility could be the result of differences in
      expression at the protein level or because other biochemical pathways or genes
      are involved in the resistance observed in clinical settings.

PMID- 16629340
TI  - Can Taenia solium latent post-oncospheral stages be found in muscle tissue of
      cysticercosis-infected pigs (Sus scrofa)?
AB  - The existence of latent Taenia solium post-oncospheral stages in the tissues of
      infected pigs has been postulated. To assess whether such structures exist and
      can be detected, we examined muscle samples from cysticercosis-infected and
      uninfected pigs. Pork samples were homogenized, centrifuged, and resuspended in
      saline solution. Round microscopic structures of approximately 10 microm with
      variable refringence were found in the pellets of all samples from both infected
      and uninfected pigs. These became homogeneously red after staining with Sudan IV
      and disappeared after ether extraction. The only difference between samples from
      infected and uninfected pigs was the presence of inflammatory cells and tissue
      necrosis debris in the former group. Taenia solium oncospheres were stained and
      observed for comparative purposes, before and after inoculation into pork.
      Control oncospheres were ellipsoidal, had nucleated basophile cells in their
      interior, and showed red aggregates on their surfaces when stained with 3% Sudan
      IV. While rounded microscopical structures similar to those previously reported
      were found, these differed morphologically from oncospheres, were of a lipid
      nature, and occurred in both infected and uninfected animals. No evidence
      supporting the presence of latent post-oncospheral stages of Taenia solium was
      generated in this series of experiments.

PMID- 16629341
TI  - Observations on the exoerythrocytic stages of different isolates of Plasmodium
      cynomolgi in hepatocytes of New World aotus and Saimiri monkeys.
AB  - Sporozoites of 3 isolates of Plasmodium cynomolgi dissected from the salivary
      glands of Anopheles dirus and Anopheles quadrimaculatus were injected
      intravenously into 9 New World monkeys. Liver stage parasites were demonstrated
      in all 9 animals; 7 of these animals also produced blood stages after prepatent
      periods of 9 to 23 days.

PMID- 16629342
TI  - Molecular confirmation of a case of multiorgan cystic echinococcosis.
AB  - We report on the results of radical surgery performed on a 10-yr-old Chinese
      female with multiple echinococcosis lesions and the diagnosis of the infection by
      imaging, histology, serology, and DNA analysis. Molecular genotyping provided
      unequivocal proof that the patient was infected with Echinococcus granulosus, the
      cause of cystic echinococcosis.

PMID- 16629343
TI  - Isolation and identification of an actin gene from Babesia gibsoni.
AB  - Actin is a ubiquitous and highly conserved microfilament protein that is
      hypothesized to play a mechanical force-generating role in the unusual gliding
      motility of sporozoan zoites and their active penetration of host cells. We have
      identified and isolated an actin gene from a Babesia gibsoni cDNA library by
      random sequencing. The complete nucleotide sequence of the actin gene is 1,243
      bp; a single open reading frame encodes a polypeptide of 377 amino acid residues.
      The deduced amino acid sequence showed a high homology with actins from other
      species, especially with reported apicomplexan protozoans. The antiserum against
      recombinant actin expressed in Escherichia coli recognizes a 42-kDa native
      protein, which is consistent with its expected size. Immunofluorescence and
      confocal microscopic observation revealed that the protein is diffusely
      distributed throughout the B. gibsoni parasites.

PMID- 16629344
TI  - Understanding immigrants' reluctance to use mental health services: a qualitative
      study from Montreal.
AB  - OBJECTIVE: Studies suggest that non-European immigrants to Canada tend to under
      use mental health services, compared with Canadian-born people. Social, cultural,
      religious, linguistic, geographic, and economic variables may contribute to this
      underuse. This paper explores the reasons for underuse of conventional mental
      health services in a community sample of immigrants with identified emotional and
      somatic symptoms. METHOD: Fifteen West Indian immigrants in Montreal with somatic
      symptoms and (or) emotional distress, not currently using mental health services,
      participated in a face-to-face in-depth interview exploring health care use.
      Interviews were analyzed thematically to discern common factors explaining
      reluctance to use services. RESULTS: Across participants' narratives, we
      identified 3 significant factors explaining their reluctance to use mental health
      services. First, there was a perceived overwillingness of doctors to rely on
      pharmaceutical medications as interventions. Second, participants perceived a
      dismissive attitude and lack of time from physicians in previous encounters that
      deterred their use of current health service. Third, many participants reported a
      belief in the curative power of nonmedical interventions, most notably God and to
      a lesser extent, traditional folk medicine. CONCLUSION: The above factors may
      highlight important areas for intervention to reduce disparities in immigrant use
      of mental health care. We present our framework as a model, grounded in empirical
      data, that further research can explore.

PMID- 16629345
TI  - The lay concept of conduct disorder: do nonprofessionals use syndromal symptoms
      or internal dysfunction to distinguish disorder from delinquency?
AB  - BACKGROUND: Conduct disorder (CD) must be distinguished from nondisordered
      delinquent behaviour to avoid false positives, especially when diagnosing youth
      from difficult environments. However, the nature of this distinction remains
      controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria
      conflict with its definition of mental disorder, which requires that symptoms be
      considered a manifestation of internal dysfunction to warrant disorder diagnosis.
      Previous research indicates that professional judgments tend to be guided by the
      dysfunction requirement, not syndromal symptoms alone. However, there are almost
      no data on lay conceptualizations. Thus it remains unknown whether judgments
      about CD are anchored in a broadly shared understanding of mental disorder that
      provides a basis for professional-lay consensus. OBJECTIVE: The present study
      tests which conception of CD, syndromal-symptoms or dysfunction-requirement,
      corresponds most closely to lay judgments of disorder or nondisorder and compares
      lay and professional judgments. We hypothesized that lay disorder judgments, like
      professional judgments, tend to presuppose the dysfunction requirement. METHOD:
      Three lay samples (nonclinical social workers, nonpsychiatric nurses, and
      undergraduates) rated their agreement that youths described in clinical vignettes
      have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria.
      Vignettes were varied to present syndromal symptoms only, symptoms suggesting
      internal dysfunction, and symptoms resulting from reactions to negative
      circumstances, without dysfunction. RESULTS: All lay samples attributed disorder
      more often to youths whose symptoms suggested internal dysfunction than to youths
      with similar symptoms but without a likely dysfunction. CONCLUSIONS: The
      dysfunction requirement appears to reflect a widely shared lay and professional
      concept of disorder.

PMID- 16629346
TI  - Factors predicting practice location and outreach consultation among University
      of Toronto psychiatry graduates.
AB  - OBJECTIVE: To identify the determinants of practice location and of outreach
      consultation of recently graduated psychiatrists. METHODS: We surveyed 153
      psychiatrists who graduated from the University of Toronto Department of
      Psychiatry between January 1990 and June 2002 (response rate 51%), on the basis
      of a self-administered mail questionnaire. The survey assessed factors that
      influenced practice location and outreach consultation, such as demographics,
      links to practice communities, and outreach experiences, including rural or
      northern electives as a resident. RESULTS: Professional variables were rated as
      the most important factors in choosing a practice location. Variables such as age
      or sex were not significantly associated with location. Nine percent reported
      working in communities of less than 100,000, and only 1% practised in Northern
      Ontario. Eighteen percent practised in the same location where they were born or
      raised. Forty-four percent had rural or northern experience as a resident but
      almost exclusively in the form of short, fly-in consultation electives. Twenty
      four percent indicated that they provide outreach consultation. Psychiatry
      residents who participated in outreach electives were 10 times as likely as those
      who did not participate to continue outreach as a consultant. CONCLUSION:
      Although early exposure to rural or northern medicine leads to significantly
      greater continued involvement in outreach activities after graduation, our
      findings suggest the need for more long-term, on-site residency training
      opportunities in rural and remote areas.

PMID- 16629347
TI  - Adult antisocial behaviour without conduct disorder: demographic characteristics
      and risk for cooccurring psychopathology.
AB  - OBJECTIVE: Several studies note people who demonstrate adult antisocial behaviour
      (AAB) in the absence of conduct disorder (CD) before age 15 years. Perhaps
      because they do not meet diagnostic criteria for antisocial personality disorder
      (ASPD), this group of people exhibiting late-onset AAB has been underrecognized
      and understudied. Thus the goal of this study was to examine the demographic
      features and patterns of cooccurring psychopathology of people exhibiting late
      onset antisocial behaviour (AB; AAB but not CD), compared with people suffering
      from ASPD (CD and AAB), people suffering from CD but not AAB, and members of a
      nonantisocial control group. METHOD: This study used the population-based sample
      of the National Comorbidity Survey (NCS). The demographic features examined were
      sex, percentage living in poverty, annual income, and years of formal education.
      The possibly cooccurring diagnoses examined were alcohol abuse and dependence,
      drug abuse and dependence, major depressive disorder, dysthymia, generalized
      anxiety disorder, social phobia, simple phobia, panic disorder, agoraphobia, and
      posttraumatic stress disorder. RESULTS: About 2.3% of participants exhibited AAB
      but not CD. These individuals had patterns of demographic characteristics and
      cooccurring psychiatric disorders quite similar to those of people diagnosed with
      full ASPD. CONCLUSION: Individuals who demonstrate this pattern of late-onset AB
      are at levels of risk comparable to those of individuals suffering from ASPD;
      therefore, they are equally in need of research and clinical attention.

PMID- 16629348
TI  - Sexual function during bupropion or paroxetine treatment of major depressive
      disorder.
AB  - OBJECTIVE: The primary objective was to evaluate sexual function (SF) separately
      in men and women with major depressive disorder (MDD) before and during treatment
      with bupropion sustained release (SR) or paroxetine. The secondary objectives
      involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the
      Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a
      comparison of antidepressant outcomes and an examination of the relation between
      level of depression and SF over time. METHOD: There were 141 patients (68 women
      and 73 men) who met DSM-IV criteria for a current major depressive episode. They
      were randomly assigned to receive bupropion SR (150 to 300 mg daily) or
      paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were
      assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton
      Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. RESULTS: Prior to
      treatment, women reported significantly lower SF on both the Sex FX and IRSD-F
      scales, compared with men. During treatment, there were no significant drug
      differences on measures of SF over time for women; however, men who were treated
      with paroxetine reported a worsening of SF, whereas bupropion SR did not
      significantly alter SF. Both bupropion SR and paroxetine produced clinically and
      statistically significant reductions in HDRS17 scores as well as comparable rates
      of response and remission. There was a statistically significant correlation
      between the 2 measures of SF at all visits. There was also a significant inverse
      relation between depression and SF in women, but not in men, irrespective of
      drug. CONCLUSION: According to the Sex FX scale, a significant difference in
      antidepressant-related sexual dysfunction was detected in men, but not women,
      during treatment with bupropion SR or paroxetine.

PMID- 16629349
TI  - Factors explaining career satisfaction among psychiatrists and surgeons in
      Canada.
AB  - BACKGROUND: The career satisfaction of specialists is affected by many variables
      ranging from family responsibilities, stress, the quality of services and
      facilities available to patients, professional rewards, and how the work is
      organized. OBJECTIVE: To articulate models that explain a substantial portion of
      the variance associated with career satisfaction among surgeons and psychiatrists
      in Canada. METHODS: Of 4958 eligible physicians across Canada, 2810 (56.7%)
      completed a 12-page survey between January and March 2004, following which the
      responding 148 surgeons and 231 psychiatrists were selected for this study. We
      checked response bias and found it was negligible. Hierarchical regression
      analysis was used to record cumulative R2, Standardized beta, and significance
      levels as each predictor was entered. We applied weighting factors to reflect the
      actual physician population in Canada. RESULTS: The models explained 90.4% of the
      variance in career satisfaction for surgeons and 81.0% of the variance in career
      satisfaction for psychiatrists. The explanatory variables consisted of distress
      and coping, role in community activities, access to and quality of health care
      services, intrinsic and extrinsic rewards, workload, and organizational
      structure. CONCLUSIONS: The study demonstrated that variance associated with
      career satisfaction can be explained using various factors reported directly by
      physicians. The study also confirmed that relative differences in the importance
      of these factors do occur among specialties. Surgeons prefer to delegate more
      responsibility in the management of their practices on an informal basis, whereas
      psychiatrists prefer to be more involved in the management of their practices and
      use more formal structures.

PMID- 16629350
TI  - Self-reported diagnoses of schizophrenia and psychotic disorders may be valuable
      for monitoring and surveillance.
AB  - OBJECTIVE: To examine whether a plausible estimate of the prevalence of
      schizophrenia can be obtained with a self-report item in a health survey.
      METHODS: We estimated a self-reported prevalence of schizophrenia, using a
      grouped variable for all people who reported schizophrenia or any other psychotic
      disorder in the Canadian Community Health Survey: Mental Health and Well-Being (n
      = 36,984). Estimates were stratified according to age, sex, and province of
      residence. RESULTS: Of survey respondents, 411 (1.1%) reported having
      schizophrenia or other psychosis, as diagnosed by a health professional; the
      weighted and adjusted estimate was 0.9% (0.7% to 1.0%). There was no statistical
      evidence that the prevalence estimates of schizophrenia and other psychosis
      varied by age, sex, or province of residence. CONCLUSIONS: Additional studies
      incorporating a gold standard diagnostic interview should be carried out to
      determine the validity of the approach. However, responses to 2 self-report
      survey items provide what appears to be a plausible epidemiologic pattern.

PMID- 16629351
TI  - Re: in debate: does psychoanalysis have a future?

PMID- 16629352
TI  - Re: CPA position statement: "The Role of Mental Health Legislation".

PMID- 16629353
TI  - Research funding key issue for ADA in 2006.

PMID- 16629354
TI  - A growing HHD market: can it continue?

PMID- 16629355
TI  - Stem cell research... the road ahead?

PMID- 16629356
TI  - Aksys vs. NxStage: a provider's experience.

PMID- 16629357
TI  - Kidney patient job retention: the next rehabilitation frontier.

PMID- 16629358
TI  - The Nurse Reinvestment Act: a promise yet unfulfilled.

PMID- 16629359
TI  - ANNA looks to nursing's future.

PMID- 16629360
TI  - Introducing case management into the outpatient dialysis center.

PMID- 16629361
TI  - Spreading the word: NBA star educates public about risk of kidney disease.
      Interview by Karen Haq.

PMID- 16629365
TI  - Water: keeping it clean for dialysis.

PMID- 16629366
TI  - Preparing for nephrology practice expansion.

PMID- 16629367
TI  - Computer technology in dialysis. Evolving needs, differing goals, and appropriate
      solutions.

PMID- 16629368
TI  - Biological and epidemiological aspects of influenza virus H5N1 in context of
      India.
AB  - Since 1997, highly pathogenic avian influenza (HPAI) H5N1 virus crossed the
      species barriers from birds to humans and caused fatal disease, leading to great
      speculation about a possible influenza pandemic. This subtype is characterized by
      its pathogenicity in a large number of animal species and resistance to older
      class of antiviral drugs. At present, two out of three general conditions for the
      onset of pandemic have been met, emergence of new virus; and its ability to
      replicate in humans causing serious illness. Next influenza pandemic might be due
      to human to human transmission. This review addresses the biological and
      epidemiological aspects of influenza in context of India.

PMID- 16629369
TI  - Occurrence of non-protein low molecular weight cardiotoxin in Indian King Cobra
      (Ophiophagus hannah) Cantor 1836, venom.
AB  - Pathophysiology due to snakebite is a combined effect of various actions of the
      complex venom constituents. Importance of protein toxins in snake envenomation is
      well known. The present investigation reports the existence of
      nonprotein/nonpetide low molecular weight toxin in Indian King Cobra venom, which
      plays an important role in envenomation consequences in experimental animal
      models. A group of non-peptidic toxins (OH-NPT1) was isolated from Indian King
      Cobra Ophiophagus hannah by thin layer chromatography and silica gel column
      chromatography. UV, IR, NMR and (ESI) TOF-MS studies characterized the OH-NPT1 as
      a mixture of aliphatic acids having molecular weights 256, 326 and 340Da. The
      minimum lethal dose of OH-NPT1 was found to be 2.5 microg/20g (iv) and
      4microg/20g (ip) in male albino mice. The cardiotoxic property of OH-NPT1 was
      established through studies on isolated guinea pig heart and auricle
      preparations, ECG studies in albino rat and estimation of LDH1/LDH and CPK-MB/CPK
      ratio in Swiss albino mice. Commercial antiserum failed to neutralize the
      lethality and cardiotoxicity of the toxin. However, calcium and magnesium
      effectively neutralized the lethal action.

PMID- 16629370
TI  - Effect of cyclooxygenase-2 (COX-2) inhibitors in various animal models
      (bicuculline, picrotoxin, maximal electroshock-induced convulsions) of epilepsy
      with possible mechanism of action.
AB  - Enzyme cyclooxygenase (COX) is reported to play a significant role in
      neurodegeneration and may play a significant role in the pathogenesis of
      epilepsy. Bicuculline (4 mg/kg; ip), picrotoxin (8 mg/kg; ip) and electroshock
      (60 mA for 0.2 sec) significantly induced convulsions in male Laka mice. COX
      inhibitors viz. nimesulide (2.5 mg/kg; ip) and rofecoxib (2 mg/kg, ip)
      administered 45 minutes prior to an epileptic challenge prolonged mean onset time
      of convulsions, decreased duration of clonus and decreased % mortality rate
      against bicuculline- and picrotoxin-induced convulsions in mice. COX-2 inhibitors
      were ineffective towards maximal electroshock-induced convulsions. Nimesulide (1
      mg/kg) and rofecoxib (1 mg/kg) also enhanced the effect of subprotective dose of
      muscimol against picrotoxin-induced convulsions. The result of the present study
      strongly suggests for a possible role of cyclooxygenase isoenzymes particularly,
      COX-2 in the pathophysiology of epilepsy and its GABAergic modulation.

PMID- 16629371
TI  - Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric
      mucosal glycoproteins, cell proliferation, antioxidants and free radicals.
AB  - Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was
      studied for its antiulcer and mucosal defensive factors in normal and non-insulin
      dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering
      streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing
      blood glucose level >140mg/dL after 12 weeks of STZ administration were
      considered as NIDDM positive. Effects of MSE were compared with known ulcer
      protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide
      (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric
      ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent
      changes in gastric mucosal glycoproteins, cell proliferation, free radicals
      (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide
      dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer
      protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU.
      NIDDM caused a significant decrease in gastric mucosal glycoprotein level without
      having any effect on cell proliferation. However, all the test drugs reversed the
      decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced
      in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO
      and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further
      increase in LPO and NO level without causing any further changes in SOD and CAT
      level. MSE pretreatment showed reversal in the levels of all the above parameters
      better than GLC. Ethanol caused a decrease in glutathione level which was further
      reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in
      both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats.
      However, SFT was ineffective in reversing the changes induced by CRS or ethanol
      or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the
      ulcer protective effect of MSE could be due to its predominant effect on mucosal
      glycoprotein, cell proliferation, free radicals and antioxidant systems.

PMID- 16629372
TI  - Antidiabetic, antihypercholesterolaemic and antioxidant effect of Ocimum sanctum
      (Linn) seed oil.
AB  - Antihyperlipidaemic and antioxidant effect of Ocimum sanctum Linn. seed oil
      (OSSO) was investigated in rabbits. Administration of OSSO (0.8 g/kg body
      weight/day) for four weeks, in cholesterol (100 mg/kg body weight/day) fed
      rabbits significantly decreased serum cholesterol, triacylglycerol and LDL-+VLDL
      cholesterol as compared to untreated cholesterol fed group. There was significant
      fall in atherogenic index in OSSO treated group. In addition, treatment with OSSO
      decreased lipid peroxidation and increased reduced glutathione content in blood.
      Antidiabetic effect of O. sanctum seed oil was evaluated in alloxan diabetic
      rabbits. Two weeks treatment of diabetic rabbits with OSSO (0.8 gm/kg/day) showed
      no significant hypoglycaemic effect. Results of the present study show that OSSO
      has hypocholesterolaemic and antioxidant effects but it does not have
      antidiabetic effect.

PMID- 16629373
TI  - Hepatoprotective activity of Psidium guajava Linn. leaf extract.
AB  - The study was designed to evaluate the hepatoprotective activity of P. guajava in
      acute experimental liver injury induced by carbon tetrachloride, paracetamol or
      thioacetamide and chronic liver damage induced by carbon tetrachloride. The
      effects observed were compared with a known hepatoprotective agent, silymarin. In
      the acute liver damage induced by different hepatotoxins, P. guajava leaf
      extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels
      of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and
      bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase
      in liver weight when compared to hepatoxin treated control, while the lower dose
      was ineffective except in the paracetamol induced liver damage. In the chronic
      liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of
      P. guajava leaf extract was found to be more effective than the lower dose (250
      mg/kg, po). Histological examination of the liver tissues supported the
      hepatoprotection. It is concluded that the aqueous extract of leaves of guava
      plant possesses good hepatoprotective activity.

PMID- 16629374
TI  - Protective effect of melatonin against propoxur-induced oxidative stress and
      suppression of humoral immune response in rats.
AB  - Effect of melatonin in attenuation of propoxur induced oxidative stress and
      suppression of humoral immune response was studied in rats. Oral administration
      of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days
      treatment. Superoxide dismutase, catalase and glutathione were also altered
      following propoxur exposure. In addition propoxur exposure markedly suppressed
      humoral immune response as assessed by antibody titre and plaque forming cell
      assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated
      the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters
      and (c) immunotoxicity. Results have been discussed in the light of possible
      immunopotentiating and antioxidant effects of melatonin to understand the
      influence of oxidative stress on propoxur induced immunomodulation.

PMID- 16629375
TI  - Immunotoxicity of phosphamidon following subchronic exposure in albino rats.
AB  - Effect of subchronic doses of phosphamidon exposure on humoral and cell mediated
      immune (CMI) responses were studied in male albino rats using SRBC, ovalbumin and
      KLH as antigens. Humoral immune responses were assessed by estimating antibody
      titre against antigen and splenic plaque forming cells (PFC) assay. CMI responses
      were studied by using leucocyte migration inhibition (LMI), macrophage migration
      inhibition (MMI) and delayed type hypersensitivity (DTH) response. Results
      obtained in the present study revealed marked suppression of humoral and CMI
      responses in a dose dependent pattern. Hence, suppression of immune responses by
      phosphamidon even at subchronic doses is clearly an important aspect for its
      safety evaluation.

PMID- 16629376
TI  - Detection of Pasteurella multocida in experimentally infected embryonated chicken
      eggs by PCR assay.
AB  - Applicability of polymerase chain reaction (PCR) assay to detect Pasteurella
      multocida in experimentally infected embryonated chicken egg was assessed in the
      present study. PCR assay rapidly and specifically detected the genome of P.
      multocida in amniotic fluid, allantoic fluid and homogenates of infected embryo
      and its membranes. The sensitivity of detection was as low as 20 bacterial
      cells/ml of allantoic or amniotic fluids. Detection of P. multocida in dead
      embryos by PCR was possible up to 6 and 30 days or more following storage of dead
      embryos at 37 degrees C, and at 4 degrees C as well as at -20 degrees C,
      respectively. The study revealed that PCR assays could be employed directly for
      detection and confirmation of P. multocida infection in experimentally infected
      chicken embryos.

PMID- 16629377
TI  - Response to complete and skeleton photoperiods in subtropical male house sparrow,
      Passer domesticus (Linnaeus).
AB  - To examine the importance of the inductive light period of a skeleton photoperiod
      in relation to the endogenous circadian rhythm of photoinducibility mediating
      photoperiodic induction, P. domesticus were exposed for 28 weeks to a series of
      skeleton photoperiods, viz. 6L:4D:1L:13D, 6L:6D:1L:11D. 6L:8D:1L:9D and
      6L:14D:1L:3D. The inductive effects of 1 hr light pulse at night varied depending
      on the time of its placement. To compare the inductive effects of complete and
      its corresponding skeleton photoperiods, birds in the second experiment were
      subjected for 20 weeks to 12L:12D and 6L:5D:1L:12D given daily or interposed on
      alternate days with constant darkness (12L:12D/DD and 6L:5D:1L:12D/DD). There was
      a difference in the rate and magnitude of response between the complete and
      skeleton photoperiods. It appears that the subtropical house sparrow uses
      photoperiodic strategy in regulation of its seasonal testicular responses similar
      to that is reported for its temperate population.

PMID- 16629378
TI  - Effect of UV-B on photosynthesis, membrane lipids and MAAs in marine
      cyanobacterium, Phormidium corium (Agardh) Gomont.
AB  - UV-B radiation (0.8 +/- 0.1 mW cm(-2)) and UV-B radiation supplemented with low
      intensity PAR (approximately 80 micro mol m(-2) s(-1)) affected photosynthesis at
      the level of antenna system as well as PS II reaction centre (Fo and Fm declined)
      in Phormidium corium (Agardh) Gomont. UV-B radiation resulted in decline in sugar
      content, peroxidation of membrane lipids as well as quantitative and qualitative
      changes in phosphoglycolipids and neutral lipids. Fatty acid profile did not show
      any qualitative changes due to the treatment, however, UV-B supplemented with low
      PAR resulted in slightly higher level of unsaturation. P. corium synthesized MAAs
      in response to UV-B. Quantity of MAAs increased when UV-B treatment was
      supplemented with low level PAR.

PMID- 16629379
TI  - Development of bioconcrete material using an enrichment culture of novel
      thermophilic anaerobic bacteria.
AB  - In the biosphere, bacteria can function as geo-chemical agents, promoting the
      dispersion, fractionation and/or concentration of materials. Microbial mineral
      precipitation is resulted from metabolic activities of microorganisms. Based on
      this biomineralogy concept, an attempt has been made to develop bioconcrete
      material incorporating of an enrichment culture of thermophilic and anaerobic
      bacteria within cement-sand mortar/concrete. The results showed a significant
      increase in compressive strength of both cement-sand mortar and concrete due to
      the development of filler material within the pores of cement sand matrix.
      Maximum strength was observed at concentration 10(5)cell/ml of water used in
      mortar/concrete. Addition of Escherichia coil or media composition on mortar
      showed no such improvement in strength.

PMID- 16629380
TI  - Siderophores of halophilic archaea and their chemical characterization.
AB  - Nine halophilic archaea viz., Halobacterium salinarum, Halobacterium sp.1,
      Halobacterium sp.2, Halobaculum sp., Halococcus saccharolyticus, Halorubrum
      saccharovorum, Haloterrigena turkmenica, Halogeometricum sp. and Natrialba sp.
      isolated from marine salterns around Bhavnagar coast were screened for
      siderophore production. Five isolates viz., Halococcus saccharolyticus,
      Halorubrum saccharovorum, Haloterrigena turkmenica, Halogeometricum sp. and
      Natrialba sp. produced siderophores as evidenced by positive reaction in FeCl3
      test, CAS assay and CAS agar plate test. Determination of chemical nature of
      siderophores by chemical assays and bioassays identified them as carboxylates.
      Quantification of siderophores indicated Halorubrum saccharovorum to be the
      maximum siderophore producer (2.62 RE mg/ml) and Halococcus saccharolyticus to be
      the least (1.33 RE mg/ml). The present study is the first report on siderophore
      production in Indian haloarchaeal strains. Mechanism of iron assimilation in four
      non-siderophore isolates still needs to be investigated further.

PMID- 16629381
TI  - The diversity of RNAi and its applications.

PMID- 16629382
TI  - Therapeutic potential of siRNA-mediated transcriptional gene silencing.
AB  - RNA interference (RNAi) and specifically the use of small interfering RNAs
      (siRNAs) represents a potentially new paradigm in gene knockout technology.
      Clearly siRNAs can be used to knockdown the expression of a targeted transcript
      in what has been termed posttranscriptional gene silencing (PTGS). While there
      are a plethora of reports applying siRNA-mediated PTGS the limitation of the
      duration of the effect remains. Recently, in human cells, siRNAs have been shown,
      similar to plants and Schizosaccharomyces pombe, to mediate transcriptional gene
      silencing (TGS). The observation that siRNAs can function in a TGS manner in
      human cells suggests that, similar to plants, human genes may also be able to be
      silenced more permanently via epigenetic modifications. The ramifications of
      siRNA-mediated TGS in humans suggest that longer term suppression of gene
      function can be obtained via siRNA-directed chromatin modifications. Undoubtedly
      the potential to employ siRNA technology is broader than once envisioned in human
      cells and suggests that siRNA-mediated TGS is not simply limited to PTGS. The
      potential to utilize siRNAs to direct epigenetic changes in local chromatin
      structure offers a new therapeutic avenue that could prove remarkably robust and
      of immeasurable therapeutic value in the directed control of target gene
      expression.

PMID- 16629383
TI  - RNA interference: a potential therapeutic tool for silencing splice isoforms
      linked to human diseases.
AB  - Alternative splicing of precursor messenger RNAs (pre-mRNAs) is one of the most
      important sources of protein diversity in vertebrates. An estimated 35%-70% of
      human genes generate transcripts that are alternatively spliced, and defects in
      this process are linked to numerous human genetic diseases and various forms of
      cancer. The discovery that 21-23 nucleotide RNA duplexes, known as small
      interfering RNAs (siRNAs), can knockdown the homologous mRNAs in mammalian cells
      has revolutionized many aspects of drug discovery including down-regulation of
      disease-associated splicing isoforms. In addition, RNA interference (RNAi)
      mediated silencing of splicing regulators has the potential to define the complex
      network of alternative splicing regulation and to analyze gene function. In this
      review, I first provide a brief introduction to mRNA splicing and its
      relationship to human diseases. This is followed by a brief overview of RNAi.
      Finally I discuss the therapeutic potential of RNAi in targeting disease-linked
      splicing isoforms.

PMID- 16629384
TI  - RNAi as a treatment for HIV-1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) was the first primate virus shown to
      be inhibited by RNA interference (RNAi). Early studies used both synthetic and
      promoter expressed small interfering RNAs (siRNAs) or expressed short hairpin
      RNAs (shRNAs) to demonstrate that this virus was susceptible to RNAi. In addition
      to targeting the virus itself RNAi-mediated down-regulation of cellular targets
      that encode receptors required for viral entry also proved to be effective. The
      power of RNAi as an anti-HIV agent has propelled development of RNAi-based gene
      therapy approaches for the treatment of HIV infection in humans. Nevertheless,
      extensive in vitro experimentation has revealed potential problems of viral
      escape mutants and other toxicities caused by the si/shRNAs. This review covers
      the progress and problems in the development of RNAi for the treatment of HIV
      infection. Potential modalities for clinical application of RNAi in the treatment
      of HIV-1 infection are also described.

PMID- 16629385
TI  - Therapeutic potential of RNAi in metabolic diseases.
AB  - Over the past years RNA interference (RNAi) has exploded as a new approach to
      manipulate gene expression in mammalian systems. More recently, RNAi has acquired
      interest as a potential therapeutic strategy. This review focuses on the
      potential therapeutic use of RNAi for metabolic diseases, the current
      understanding of RNAi biology, and how RNAi has been utilized to study the role
      of different genes in the pathogenesis of diabetes and obesity. Also reviewed are
      the in vivo proof-of-principle experiments that provide the preclinical
      justification for the development of RNAi-based therapeutics for diabetes and the
      key challenges that currently limit its application in the clinical setting.

PMID- 16629386
TI  - Toward silencing the burden of malaria: progress and prospects for RNAi-based
      approaches.
AB  - The discovery of RNA interference (RNAi) is one of the most significant of recent
      years, with potential for application beyond the laboratory to the clinic. As a
      tool for functional genomics, RNAi has permitted the characterization of genes in
      organisms that had previously remained recalcitrant to targeted gene
      manipulation. Efforts to understand its mode of action have revealed a central
      role in gene regulation and host defense. Finally, as a therapeutic tool, it has
      shown enormous promise in the control of a large array of diseases. Here we
      examine how RNAi is revolutionizing malaria research in an organism, the
      Anopheles mosquito, that until recently was essentially resistant to genetic
      study, and show how its application in both the mosquito vector and the
      Plasmodium parasite might ultimately lead to new ways of controlling and perhaps
      even eradicating this devastating disease.

PMID- 16629387
TI  - Anything can work.

PMID- 16629388
TI  - Protein microarrays.

PMID- 16629389
TI  - One-step high-throughput assay for quantitative detection of beta-galactosidase
      activity in intact gram-negative bacteria, yeast, and mammalian cells.

PMID- 16629390
TI  - Evaluation method of ordinary flatbed scanners for quantitative density analysis.

PMID- 16629391
TI  - Device for handling electron microscopy grids.

PMID- 16629392
TI  - Alkaline polyethylene glycol-based method for direct PCR from bacteria,
      eukaryotic tissue samples, and whole blood.

PMID- 16629393
TI  - Phage Bxb1 integrase mediates highly efficient site-specific recombination in
      mammalian cells.

PMID- 16629394
TI  - Amplification and analysis of cDNA generated from a single cell by 5'-RACE:
      application to isolation of antibody heavy and light chain variable gene
      sequences from single B cells.
AB  - The technique of 5'-rapid amplification of cDNA ends (5'-RACE) is widely used to
      amplify unknown sequences at the 5' end of a messenger RNA (mRNA). However,
      conventional 5'-RACE is inappropriate for producing cDNAs from a single cell due
      to the small quantity of mRNA present in one cell. In this study, we report an
      improved 5'-RACE method that is suitable for generating cDNA from a single cell.
      In this method, the first-strand cDNA was directly synthesized from a single
      cell, and both the tailing reaction and second-strand cDNA synthesis were
      performed in the same tube without purifying the cDNA sample. Using this method,
      we were able to amplify the cDNA of the immunoglobulin (Ig) variable region gene
      from more than 50% of single B cells. The amplified cDNA fragment contained a
      full-length Ig variable region including a 5'-untranslated region, a leader
      sequence, and an initiation codon. This method may thus be applicable for a
      comprehensive analysis of the Ig variable genes of the lymphocyte repertoire in
      humans and animals, thereby contributing to the development of antibody-based
      therapeutics for infectious diseases.

PMID- 16629395
TI  - Direct quantification of gene expression in homogenates of formalin-fixed,
      paraffin-embedded tissues.
AB  - Formalin-fixed, paraffin-embedded (FFPE) tissues represent an important source of
      archival materials for gene expression profiling. We report here the development
      of a modified branch DNA assay that allows direct quantification of messenger RNA
      (mRNA) transcripts in homogenates from FFPE tissue sections without the need for
      RNA isolation and reverse transcription into cDNA. Formalin fixation essentially
      has no effect on the branch DNA assay, and RNA degradation only marginally
      reduces the signal by 2- to 3-fold. Under the same conditions, formalin fixation
      and RNA degradation greatly reduces real-time reverse transcription PCR (RT-PCR)
      efficiency, reducing signals by as much as 15- and 1400-fold, respectively.
      Although both technologies can generate biologically meaningful expression
      profiles from FFPE human lung tumor specimens, the branch DNA assay is more
      sensitive than real-time RT-PCR under the conditions tested. Our results
      therefore suggest that the branch DNA assay is an ideal tool for retrospective
      analysis of gene expression in archival tissues.

PMID- 16629396
TI  - Advances in fluorescent tracking of nucleic acids in living cells.
AB  - Nucleic acids are typically detected in morphologically preserved fixed cells and
      tissues using in situ hybridization techniques. This review discusses a variety
      of established and more challenging fluorescence-based methods for the detection
      and tracking of DNA or RNA sequences in living cells. Over the past few years,
      various fluorescent in vivo labeling methods have been developed, and dedicated
      microscope and image analysis tools have been designed. These advances in
      technologies indicate that live-cell imaging of nucleic acids is likely to become
      a standard research tool for understanding genome organization and gene
      expression regulation in the near future. Recent live-cell imaging studies have
      already provided important insights into the dynamic behaviors of chromatin and
      RNAs in the cell.

PMID- 16629397
TI  - Detection of high levels of recombination generated during PCR amplification of
      RNA templates.
AB  - Recombination during the PCR amplification of DNA templates can be a serious
      problem for those seeking to genotype heterogeneous populations, yet a boon to
      those seeking to enhance variation during in vitro evolution. Here, the extent to
      which PCR generates chimeric full-length products was estimated using a powerful
      restriction fragment-length polymorphism (RFLP) assay involving the use of
      fluorescently labeled PCR primers. Three different RNA-encoding DNA templates
      were assayed: (i) one for a group I ribozyme, (ii) one for a 16S ribosomal RNA
      (rRNA), and (iii) one for a messenger RNA (mRNA). In all cases, the observed
      frequency of chimeric PCR products exceeded 20%, and longer templates appear to
      produce more chimeric products. Although two of these templates have the
      potential to form secondary structures during the PCR, this tendency does not
      seem to heighten recombination frequency. These results corroborate previous
      studies that show that the production of chimeras can be best attenuated to a
      certain extent by varying the extension times in PCR.

PMID- 16629398
TI  - Use of a zinc fluorophore to measure labile pools of zinc in body fluids and cell
      conditioned media.
AB  - Here we describe a rapid and sensitive zinquin-based fluorometric assay that
      enables one to monitor levels of labile Zn(II) in body fluids, buffers, and cell
      conditioned culture media as well as changes in these pools in disease. Labile
      pools of Zn(II) are free or loosely bound pools and more tightly bound but
      zinquin-accessible pools in contrast to the fixed pools of Zn(II) within
      metalloproteins. In human plasma, mean labile Zn(II) was 8.1 microM (SEM 0.53; n
      = 81) and constituted about 70% of the total plasma Zn(II) and >90% of human
      plasma albumin Zn(II). Plasma labile Zn(II) was significantly depleted after 7
      days of Zn(II) deprivation in mice, despite only small changes in body weight.
      Labile Zn(II) concentrations were also measured in the induced sputum plugs,
      saliva, and urine of normal adults and were 1.30 microM (SEM 0.27; n = 73), 0.11
      microM (SEM 0.11; n = 6), and 0.23 microM (SEM 0.08; n = 8), respectively.
      Urinary labile Zn(II) concentration was significantly increased in some patients
      with type II diabetes mellitus (overall mean was 0.90 microM, SEM 0.30; n = 12).
      The technique may be particularly useful in assessing extracellular Zn(II) levels
      in diseases associated with altered Zn(II) homeostasis, identifying those
      subjects most in need of Zn(II) supplementation, and defining the optimum
      concentrations of available Zn(II) in buffers and culture media.

PMID- 16629399
TI  - Cell adhesion profiling using extracellular matrix protein microarrays.
AB  - We have developed a microarray-based system for cell adhesion profiling of large
      panels of cell-adhesive proteins to increase the throughput of in vitro cell
      adhesion assays, which are currently primarily performed in multiwell plates.
      Miniaturizing cell adhesion assays to an array format required the development of
      protocols for the reproducible microspotting of extracellular matrix (ECM)
      protein solutions and for the handling of cell suspensions during the assay. We
      generated ECM protein microarrays with high reproducibility in microspot protein
      content using nitrocellulose-coated glass microslides, combined with
      piezoelectric microspotting of protein solutions. Protocols were developed that
      allowed us to use 5000 cells or fewer on an array of 4 x 4 mm consisting of 64
      microspots. Using this microarray system, we identified differences of adhesive
      properties of three cell lines to 14 different ECM proteins. Furthermore, the
      sensitivity and accuracy of the assays were increased using microarrays with
      ranges of ECM protein amounts. This microarray system will be particularly useful
      for extensive comparative cell adhesion profiling studies when only low amounts
      of adhesive substrate and cells, such as stem cells or cells from biopsies, are
      available.

PMID- 16629400
TI  - Testing the indifferentiation hypothesis during childhood, adolescence, and
      adulthood.
AB  - The general (g) factor is the most general and relevant cognitive ability. This
      factor is considered to be one of the most important predictors of academic
      achievement and of many other socially relevant behavioral outcomes. In the last
      decades, many researchers have investigated the possible changes in the relevance
      of the g factor from childhood to adulthood. The indifferentiation hypothesis
      states that the variance attributed to the g factor and the main cognitive
      abilities will not change over the life span. In the present study, the authors
      tested that hypothesis in childhood, adolescence, and adulthood by using 2
      different cognitive batteries (Test of Educational Ability [TEA; S. A. TEA,
      1999], Wechsler Adult Intelligence Scales [WAIS; D. Wechsler, 1955]), which they
      administered in 2 different countries--Spain (TEA) and the United States (WAIS).
      The ages of the participants (N = 2,384) ranged from 8 to 54 years. Results
      showed that the number of factors extracted and the relevance were the same for
      every age group in both batteries, as predicted by the indifferentiation
      hypothesis. The authors discuss implications of intelligence assessment.

PMID- 16629401
TI  - An investigation of the fantasy predisposition and fantasy style of children with
      imaginary companions.
AB  - In this study, the author tested whether children with imaginary companions (ICs)
      have a different fantasy life than do children without ICs. To measure the
      fantasy life of the 74 children aged 3.2 to 8.7 years, the author modified the
      Children's Fantasy Interview (E. Rosenfeld, L. R. Huesmann, L. D. Eron, & J. V.
      Torney-Purta, 1982) to make it suitable for young children and focused on 5
      aspects of fantasy life: (a) ICs, (b) dreams, (c) daydreams, (d) scary thoughts,
      and (e) pretend games. Consistent with the hypothesis, children who had ICs were
      more likely than were children without ICs to report (a) vivid imagery when
      daydreaming, (b) vivid imagery when playing pretend games, (c) mythical content
      for dreams, and (d) mythical content for pretend games.

PMID- 16629402
TI  - Mathematics beliefs and achievement of elementary school students in Japan and
      the United States: results from the Third International Mathematics and Science
      Study.
AB  - Student self-beliefs are significantly related to several types of academic
      achievement. In addition, results from international assessments have indicated
      that students in Japan have typically scored above international averages (D. L.
      Kelly, I. V. S. Mullis, & M. O. Martin, 2000). In this study, the author examined
      relationships between mathematics beliefs and achievement of elementary school
      aged students in the United States and Japan. The students had participated in
      the Third International Mathematics and Science Study (TIMSS; A. E. Beaton et
      al., 1996). The author examined several self-beliefs and used variance estimation
      techniques for complex sampling designs. The author identified a number of
      significant relationships between self-beliefs and mathematics achievement.
      Students who attributed success in mathematics to controllable factors (e.g.,
      hard work, studying at home) showed higher test scores whereas students who
      attributed success in mathematics at school to external factors (e.g., good luck)
      tended to earn lower mathematics test scores. These results extend the findings
      of previous research results because the author examined large national samples
      of students in cross-cultural settings as part of a comprehensive international
      assessment.

PMID- 16629403
TI  - The relation between dimensions of attachment and internalizing or externalizing
      problems during adolescence.
AB  - The authors examined the relation between dimensions of attachment and
      internalizing and externalizing problems in 15- to 16-year-old adolescents (n =
      62) who completed the Attachment Style Questionnaire (ASQ; J. Feeney, P. Noller,
      & M. Hanrahan, 1994) and the Youth Self-Report (YSR; T. M. Achenbach, 1991). In
      total, the ASQ dimensions accounted for 48% of the variance in scores on the
      broad YSR internalizing problem scale. Three ASQ dimensions (confidence,
      discomfort with closeness, preoccupation with relationships) accounted for unique
      variance. Girls exhibited higher problem scores than did boys even when the
      authors considered ASQ scores. The authors observed comparable results for the
      anxious/depressed subscales. The confidence, discomfort, and preoccupation
      dimensions predicted scores on the withdrawn subscale. The authors observed weak
      relations or no relations between results on the ASQ and the externalizing
      problems scale. In conclusion, dimensions of attachment are powerful predictors
      of internalizing problems in adolescents. The authors discussed the potential
      cause and effect relationship between attachment variables and self-reported
      problems.

PMID- 16629404
TI  - Exploratory and confirmatory factor analyses of the pervasive developmental
      disorders rating scale for young children with autistic disorder.
AB  - In this study, the authors examined the construct validity of the Pervasive
      Developmental Disorder Rating Scale (PDDRS; R. C. Eaves, 1993), which is a
      screening instrument used to identify individuals with autistic disorder and
      other pervasive developmental disorders. The PDDRS is purported to measure 3
      factors--arousal, affect, and cognition-that collectively make up the construct
      of autism. Using scores from 199 children (aged 1-6 years) diagnosed with
      autistic disorder, the authors submitted data to exploratory and confirmatory
      factor analyses. In the 1st series of analyses, the authors analyzed a user
      specified 3-factor solution using principal axis factor analysis with a promax
      rotation to evaluate the assertion of a correlated 3-factor structure. Next, the
      authors analyzed 1-factor and 2-factor solutions to determine if they provided a
      better factor structure for the data. In the 2nd series, the authors conducted
      confirmatory factor analyses, which compared the theorized hierarchical 2nd-order
      factor model with 5 plausible competing models. The results of the exploratory
      analyses supported the 3-factor solution. With the confirmatory analyses, the 2nd
      order factor model provided the best fit for the data. The exploratory and
      confirmatory analyses supported the theoretical assumptions undergirding the
      development of the PDDRS. The authors discuss theoretical implications, practical
      implications, and areas for further research.

PMID- 16629405
TI  - Classroom racial proportion: influence on self-concept and social competence in
      Zimbabwean adolescents.
AB  - The authors measured self-concept and social competence relationships in 372
      Zimbabwean adolescents (41% Black, 59% White) who attended classrooms in which
      they were either a racial minority or a racial majority (M age = 12.95 years, SD
      = 1.47). The authors used self-, peer-, and teacher-rating scale sociometric
      measures of social competence and a multidimensional measure of self-concept. The
      regression analysis predicted self-concept from social competence measures.
      Teacher-rated social competence predicted physical appearance self-concept in the
      Black adolescents and reading self-concept in White adolescents in White-majority
      classrooms. Self-rated social competence and peer-rated social competence
      predicted school self-concept in Black adolescents attending Black-majority
      classrooms. The authors concluded that classroom racial proportions influence
      aspects of social perception of Black and White adolescents.

PMID- 16629406
TI  - Inhibition of beta-1,3-glucan synthase and cell growth of Cryptococcus species by
      recombinant single-chain anti-idiotypic antibodies.
AB  - Recombinant single-chain fragment variable (scFv) anti-idiotypic antibodies were
      produced to represent the internal image of a HM-1 killer toxin, which is
      characterized by a wide spectrum of anti-fungal activity through inhibiting beta
      1,3-glucan synthase (GS). We examined if scFv antibodies are active against
      Cryptococcus species, a human pathogen of increasing medical importance. The anti
      cryptococcal activity of scFv antibodies and HM-1 were assessed by MIC analysis
      for C. neoformans IFM 40215 and C. albidus NBRC 0612 cells. The scFv antibodies
      had strong anti-cryptococcal activity in vitro with IC50 at 1.07 x 10(-7) to 2.60
      x 10(-7) M for C. neoformans and C. albidus. Furthermore, the scFv antibodies
      potentially inhibited GS of C. neoformans with IC50 at 1.27 x 10(-7) to 2.27 x
      10(-7) M. Both the anti-fungal and anti-GS activities of the scFv antibodies were
      markedly neutralized by the monoclonal antibody that neutralizes HM-1 killer
      toxin.

PMID- 16629407
TI  - In vitro time-kill activities of rifalazil, alone and in combination with
      vancomycin, against logarithmic and stationary cultures of Staphylococcus aureus.
AB  - Rifalazil is a novel rifamycin that, like other members of this class, inhibits
      bacterial transcription by targeting the beta subunit of prokaryotic DNA
      dependent RNA polymerase. To address the high-frequency resistance seen with
      rifamycins, we assessed the ability of rifalazil, alone and in combination with
      vancomycin, to both kill cells and to suppress the appearance of resistant
      mutants in log and stationary phase Staphylococcus aureus cultures, using high
      cell densities in an in vitro kill curve model. We found that (1) rifalazil alone
      killed log-phase cultures more rapidly than rifampicin, but both drugs quickly
      selected for resistant mutants, (2) co-treatment of log phase cultures with
      rifalazil and vancomycin increased bacterial killing by about 3-Log10 over either
      drug used alone and delayed the appearance of rifamycin-resistant mutants, (3)
      rifalazil and vancomycin in combination killed stationary phase cultures

PMID- 16629408
TI  - New aminophenoxazinones from a marine Halomonas sp.: fermentation, structure
      elucidation, and biological activity.
AB  - The addition of anthranilic acid to the culture medium of the marine derived
      Halomonas sp. strain GWS-BW-H8hM completely altered the secondary metabolite
      pattern relative to the standard conditions. The red-orange color of the culture
      filtrate extract was the result of the production of 2-aminophenoxazin-3-one (1),
      chandrananimycin C (5) and three new derivatives of 1 with a previously unknown
      substitution pattern: 2-amino-, 2-amino-8-benzoyl-, and 2-amino-8-(4
      hydroxybenzoyl)-6-hydroxyphenoxazin-3-one (2-4). The compounds were determined to
      have antibacterial and cytotoxic activities; a mode of action other than DNA
      intercalation is discussed.

PMID- 16629409
TI  - Sespendole, a new inhibitor of lipid droplet synthesis in macrophages, produced
      by Pseudobotrytis terrestris FKA-25.
AB  - Sespendole was isolated as an inhibitor of lipid droplet formation in macrophages
      from the culture broth of a fungal strain Pseudobotrytis terrestris FKA-25. The
      compound inhibited the synthesis of cholesteryl ester and triacylglycerol by
      mouse macrophages with IC50 values of 4.0 and 3.2 microM, respectively.

PMID- 16629410
TI  - Synthesis of 2-methyl 16-membered macrolide derived from tylosin.
AB  - To improve the metabolic stability of a 16-membered macrolide, 2-methylated
      derivatives of desmycosin were synthesized. Among these derivatives, 2beta
      methyldesmycosin retained antibacterial activity and showed improved stability in
      rat serum compared to desmycosin.

PMID- 16629411
TI  - The structures of fluostatins C, D and E, novel members of the fluostatin family.
AB  - Three new fluostatin antibiotics have been isolated from the culture filtrate of
      Streptomyces strain Acta 1383. The chemical structures of these compounds were
      determined by mass spectrometry and NMR spectroscopy. The relative configuration
      has been determined by X-ray crystal structure analysis and the absolute
      configuration was deduced from NMR data with the help of Helmchen esters. These
      compounds represent the first reported epoxide fluostatins (1, 2) and underline
      previously found analogies to the group of kinamycin antibiotics.

PMID- 16629412
TI  - Hirsutenols D, E and F, new sesquiterpenes from the culture broth of Stereum
      hirsutum.
AB  - New sesquiterpenes, hirsutenols D-F, were isolated from the fermentation broth of
      Stereum hirsutum, and their structures were determined on the basis of various
      spectroscopic analyses. Hirsutenols E and F showed significant scavenging
      activity against superoxide anion radicals with EC50 values of 1.62 and 0.39 mM,
      respectively.

PMID- 16629413
TI  - Effects of 2'-demethoxy-2'-propoxygriseofulvin on microtubule distribution in
      Chinese hamster V79 cells.
AB  - Griseofulvin may combine with tubulin as a component of microtubules and, at high
      doses, inhibits microtubule formation in mammalian cells. In this study, the
      author examined the effects of three various 2'-substitutive derivatives of
      griseofulvin on microtubule distribution in Chinese hamster V79 cells. The
      results showed that 2'-demethoxy-2'propoxygriseofulvin was the strongest
      inhibitor of a normal cytoplasmic microtubule network, unlike findings in
      previous in-vitro studies.

PMID- 16629414
TI  - Self-activation of serine/threonine kinase AfsK on autophosphorylation at
      threonine-168.
AB  - A Hanks-type protein kinase AfsK autophosphorylates on threonine residue(s) and
      phosphorylates AfsR, a global regulator for secondary metabolism in Streptomyces
      coelicolor A3(2). Mass spectrometry of a tryptic digest of the autophosphorylated
      form of AfsK deltaC corresponding to the kinase catalytic domain (Met-1 to Arg
      311) of AfsK, together with subsequent site-directed mutagenesis of the candidate
      amino acids, identified threonine-168 as a single autophosphorylation site.
      Threonine-168 is located in the activation loop that is known for some Ser/Thr
      kinases to modulate kinase activity on phosphorylation of one or more threonine
      residues within the loop. Consistent with this, mutant T168D, in which Thr-168
      was replaced by Asp, became a constitutively active kinase; it phosphorylated
      AfsR to the same extent as AfsK deltaC produced in and purified from Escherichia
      coli cells during which a considerable population of it had been already
      phosphorylated intermolecularly. All these findings show that autophosphorylation
      or intermolecular phosphorylation of threonine-168 in AfsK accounts for the self
      activation of its kinase activity.

PMID- 16629415
TI  - The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of
      the acute MS lesion.
AB  - Advances in the neuropathology of multiple sclerosis (MS) have contributed
      greatly to our understanding of the mechanisms of tissue injury in the condition.
      Particular interest has focussed on the active MS lesion, defined by macrophage
      activity in the presence of partially demyelinated axons. This has led to the
      prevailing consensus that a T-cell dependent, macrophage-mediated, autoimmune
      attack on constituents in the normal myelin sheath underlies the disease. This
      hypothesis, which has been largely supported by comparisons with the animal
      model, experimental allergic encephalomyelitis, has recently been questioned by
      an analysis of the pathological events preceding myelin phagocytosis in nascent
      MS lesions. The prephagocytic changes in evolving lesions examined shortly after
      the onset of an MS relapse raise the possibility that oligodendrocyte cell death
      and associated changes within the myelin sheath initiate local macrophage
      scavenger activity, with subsequent amplification of the inflammatory response.
      The presence of such lesions in patients with a spectrum of pathological changes
      in nearby or distant active phagocytic plaques suggests that pathological
      heterogeneity in MS is largely due to evolution of lesional pathology, rather
      than pathogenic heterogeneity.

PMID- 16629416
TI  - Human demyelinating disease and the polyomavirus JCV.
AB  - Many human neurological diseases involve demyelination of the central and/or
      peripheral nervous systems. These include the hereditary leukodystrophies--which
      have a genetic basis; multiple sclerosis (MS)--where the underlying cause of
      demyelination remains unknown; and progressive multifocal leukoencephalopathy
      (PML)--where the etiology is well-established as being viral. The human
      neurotropic polyomavirus--JC virus (JCV)--is the etiologic agent of PML, a fatal
      demyelinating disease of the central nervous system that occurs mainly in
      immunosuppressed patients, especially those with HIV/AIDS. JCV belongs to the
      polyomavirus family of tumor viruses that are characterized by non-enveloped
      icosahedral capsids containing small, circular, double-stranded DNA genomes.
      Serological studies have shown that JCV is widespread throughout the human
      population, but infections are usually restricted by the immune system,
      particularly cell-mediated immunity, causing the virus to enter a latent phase.
      An important corollary of this is that situations of severe immunosuppression may
      permit JCV to replicate and are thus a risk factor for PML.

PMID- 16629417
TI  - Axonal damage markers in the cerebrospinal fluid of patients with clinically
      isolated syndrome improve predicting conversion to definite multiple sclerosis.
AB  - Clinically isolated syndrome (CIS) represents the earliest phase of multiple
      sclerosis (MS). This study tested whether biomarkers for axonal degeneration can
      improve upon sensitivity and specificity of magnetic resonance imaging (MRI)
      parameters in predicting conversion from CIS to MS. Patients with CIS (n = 52),
      relapsing-remitting MS (RRMS, n = 38) and age-matched controls (n = 25) were
      included. Cerebrospinal fluid (CSF) levels of tau and neurofilaments (NfHSMI35)
      were measured using ELISA. The MRI T2-lesion load and the Expanded Disability
      Status Scale (EDSS) were recorded. CSF tau and NfHSMI35 were elevated in CIS
      compared to controls (P<0.05). RRMS patients with acute relapse had higher
      NfHSMI35 levels than stable patients. Tau and NfHSMI35 levels correlated with
      EDSS in CIS and RRMS. In RRMS, the number of T2-lesions correlated with tau
      levels (R = 0.53, P = 0.01). The sensitivity predicting the conversion from CIS
      to MS was higher for the combination of CSF markers (either tau or NfHSMI35
      elevated) than for MRI (40 versus 34%), but could be further increased to 60% if
      CSF and MRI criteria were combined. Similarly, the combination of tau and
      NfHSMI35 showed higher specificity (94%) than MRI (82%). Tau and NfHSMI35 are
      valuable biomarkers for axonal damage in the CIS patients. Predicting conversion
      from CIS to MS can be improved if CSF markers are combined with MRI.

PMID- 16629418
TI  - Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on
      early gene expression for immune-related molecules by central nervous system
      mixed glial cell cultures.
AB  - Cytokines secreted within the central nervous system (CNS) are important in the
      development of multiple sclerosis (MS) lesions. The balance between Th1,
      monocyte/macrophage (M/M) and Th2 cytokines in the CNS may be pivotal in
      determining the outcome of lesion development. We examined the effects of
      mixtures of cytokines on gene expression by CNS glial cells, as mixtures of
      cytokines are present in MS lesions, which in turn contain mixtures of glial
      cells. In this initial analysis by gene array, we examined changes at 6 hours to
      identify early changes in gene expression that represent primary responses to the
      cytokines. Rat glial cells were incubated with mixtures of Th1, M/M and Th2
      cytokines for 6 hours and examined for changes in early gene expression employing
      microarray gene chip technology. A minimum of 814 genes were differentially
      regulated by one or more of the cytokine mixtures in comparison to controls,
      including changes in expression in a large number of genes for immune system
      related proteins. Expression of the proteins for these genes likely influences
      development and inhibition of MS lesions as well as protective and regenerative
      processes. Analysing gene expression for the effects of various combinations of
      exogenous cytokines on glial cells in the absence of the confounding effects of
      inflammatory cells themselves should increase our understanding of cytokine
      induced pathways in the CNS.

PMID- 16629419
TI  - Idiopathic acute transverse myelitis: a clinical study and prognostic markers in
      45 cases.
AB  - OBJECTIVE: The Transverse Myelitis Consortium Working Group has proposed new
      diagnostic criteria for idiopathic acute transverse myelitis (ATM). We reviewed
      patients admitted to our center diagnosed with myelitis with two objectives: (i)
      to evaluate the usefulness of these criteria in distinguishing between myelitis
      as the first episode of multiple sclerosis (MS) and idiopathic ATM; and (ii) to
      analyse the clinical and laboratory variables that may be used as functional
      prognostic markers. METHODS: We selected patients who met the criteria. We
      recorded clinical epidemiological data, patients treated with methylprednisolone,
      maximal disability reached and disability at final follow-up. We also recorded
      cerebrospinal fluid (CSF) data and the number of levels affected in the spinal
      magnetic resonance imaging (MRI). RESULTS: Twenty-four patients fulfilled the
      criteria for definite ATM and 21 for possible ATM. Five patients converted to MS.
      Mean follow-up time was 3.5 years. There was an association between younger
      patients and female patients with conversion to MS. The highest Rankin score
      reached and increased CSF glucose levels were associated with a poor outcome. In
      multivariate analysis, only the admission Rankin score was associated with
      outcome. CONCLUSIONS: (i) About 10% of patients who met the criteria may convert
      to MS; and (ii) admission Rankin score was the only independent prognostic factor
      found.

PMID- 16629420
TI  - Survival, and time to an advanced disease state or progression, of untreated
      patients with moderately severe multiple sclerosis in a multicenter observational
      database: relevance for design of a clinical trial for high dose
      immunosuppressive therapy with autologous hematopoietic stem cell
      transplantation.
AB  - Despite prolonged survival, patients with multiple sclerosis (MS) experience
      considerable morbidity, which adversely impacts quality of life. To assess the
      risk-benefit of a clinical trial of high dose immunosuppressive therapy with
      autologous hematopoietic stem cell transplantation for MS, we sought to determine
      the natural history of the disease in a comparison group of untreated patients.
      We identified 285 individuals with 2132 combined observation years (median: 5.6
      years; 5th to 95th percentile: 1-21 years), with Expanded Disability Status Scale
      (EDSS) scores of 3.0-5.5 at baseline observation. Disease-related mortality was
      zero at five years, 5.4% at 10 years, and 22% at 15 years (40 patients
      contributing to the data point; 95% confidence interval: 4-32%). Risk for
      progression to advanced disability, defined as an EDSS score of 8, was very low
      for the subgroup with a baseline EDSS score of 3-3.5; however, for those with a
      baseline EDSS score of 4-5.5, 3% had advanced disability after two years, 5%
      after three years, 6% after four years, 12% after five years, and 40% after 10
      years. The estimated probability of disease progression, defined as an increase
      in EDSS score by > or = 1.0 sustained for at least 180 days, was 5% after one
      year, 14% after two years, 22% after three years, 38% after five years, 57% after
      10 years, and >80% after 20 years of observation. The relevance of these features
      to the design of the clinical trial is discussed.

PMID- 16629421
TI  - Change in clinician-assessed measures of multiple sclerosis and subject-reported
      quality of life: results from the IMPACT study.
AB  - BACKGROUND: The IMPACT study demonstrated the benefit of interferon beta-1a
      (IFNbeta-1a, Avonex) two-year change in disability measured by the Multiple
      Sclerosis Functional Composite (MSFC) in secondary progressive multiple sclerosis
      (SP-MS) and health-related quality of life (HRQoL) measured by the Multiple
      Sclerosis Quality of Life Inventory (MSQLI). The IMPACT data permit a detailed
      assessment of the relation between clinical and self-reported measures. METHODS:
      IMPACT was an international randomized, double-blind, placebo-controlled trial of
      SP-MS patients. As the MSQLI is only in English, this report includes US and
      Canadian subjects. Subjects were randomized to weekly intramuscular (im)
      injections of INbeta-1a (60 microg) or placebo for 24 months. RESULTS: At
      baseline and follow-up, MSQLI correlations were generally stronger with the EDSS
      than with the MSQLI, MSFC but comparable with MSFC components. Combining the two
      groups, MSQLI changes for those in the best and worst MSFC change quartiles
      demonstrated a statistical difference for six of the 11 MSQLI scales. Linear
      regression demonstrated that EDSS change from baseline to month-24 scores was
      correlated with change in two MSQLI components. CONCLUSION: These data support
      the appropriateness of using the MSQLI with individuals who have SP-MS.

PMID- 16629422
TI  - Cognitive impairment in patients with multiple sclerosis using the Brief
      Repeatable Battery-Neuropsychology test.
AB  - AIMS: To assess the cognitive impairment of multiple sclerosis (MS) patients
      using the Brief Repeatable Battery-Neuropsychology (BRB-N) test. METHODS: The
      performance of 59 patients with MS in the BRB-N test was assessed and compared
      with 152 matched healthy controls (HC). RESULTS: In most tests, MS patients
      performed worse than controls. Age and educational level strongly influenced the
      performance of the subjects. The Symbol Digit Modality Test (SDMT) best
      correlated with the other individual tests and contributed most to the general
      BRB-N factor. Furthermore, a correlation between physical disability and
      performance in some BRB-N tests was observed. Indeed, patients with progressive
      MS and greater physical disability performed worse in some tests than less
      disabled patients with relapsing MS. By creating a global BRB-N Z score, we found
      that patients generally performed 0.7 standard deviation (SD) below the level of
      controls. We obtained cut-off values stratified by age and education to
      determinate cognitive impairment in MS patients. CONCLUSIONS: Our data show that
      cognitive impairment is prevalent amongst MS patients, and that a single
      cognitive measurement might be useful for monitoring patients during the
      progression of this illness.

PMID- 16629423
TI  - Worries and concerns of patients with multiple sclerosis: development of an
      assessment scale.
AB  - This study examined the nature of worry in adult patients with multiple sclerosis
      (MS) in the UK. A measure of worry in MS was developed and the relationship
      between worry and standard scale measures of anxiety and depression was examined.
      Thirty-nine patients with MS and 40 controls completed the new worry scale (WQMS)
      that was psychometrically evaluated, together with the Penn State Worry
      Questionnaire (PSWQ), the Hospital Anxiety and Depression Scale (HAD) and a
      previously developed scale to assess self-efficacy in MS (SESMS). The scores for
      both anxiety (t = 2.34; P < 0.05) and depression (t = 5.52; P <0.01) were higher
      in MS patients than controls, as was the new scale for worry--the WQMS. A factor
      analysis (explaining 65.73% of the variance) suggests that the worries of
      patients may be dichotomized into those concerned with the physical effects of
      the disease and those relating to the impact on social interaction, family
      relationships and daily activity in the home and/or work. Worry in patients with
      MS was associated with a decreased sense of being able to produce positive
      activities or effect positive outcomes (low self-efficacy). The questionnaire
      provides a framework for investigation in clinic of specific concerns and level
      of worry they engender.

PMID- 16629424
TI  - Treatment of depression for patients with multiple sclerosis in neurology
      clinics.
AB  - The objective of this study was to examine the adequacy of antidepressant
      pharmacotherapy in a sample of patients with multiple sclerosis (MS) treated by
      neurologists. METHODS: MS patients under the care of neurologists were recruited
      from a large health maintenance organization. Major depressive disorder (MDD) was
      diagnosed using a structured telephone interview. Antidepressant treatment data
      were obtained from the HMO pharmacy database. RESULTS: Study participants
      included 260 patients with MS treated by 35 neurologists. A total of 67 (25.8%)
      patients met the criteria for MDD. Among the patients with MDD, 65.6% received no
      antidepressant medication, 4.7% received subthreshold doses from their
      neurologists, 26.6% received doses at threshold, and 3.1% received doses
      exceeding threshold. DISCUSSION: Depression was undertreated by the neurologists
      treating this sample of patients with comorbid MS and MDD. Potential solutions
      are discussed.

PMID- 16629425
TI  - Multiple sclerosis patients with and without sexual dysfunction: are there any
      differences?
AB  - OBJECTIVE: Sexual dysfunction (SD) severely affects the quality of life in
      patients with multiple sclerosis (MS). The aim of this study is to investigate
      the type and frequency of sexual complaints in MS patients, to analyse their
      relationship to various clinical and psychosocial variables and to clarify the
      differences between MS patients with and without SD. METHODS: Thirty-five
      relapsing-remitting (RR), nine secondary progressive and seven primary
      progressive MS patients were included in this study. A structured face-to-face
      interview regarding sexual function and other physical problems which may
      interfere with sexual functioning was administered to each patient. They also
      filled out Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19),
      which includes items for primary (direct physical), secondary (indirect physical)
      and tertiary (psychosocial) causes of SD. Disability, cognitive functions and
      psychological functioning were also evaluated. RESULTS: Forty-one patients
      (80.4%) reported primary SD; decreased libido was the most frequent complaint
      (80.5%). These patients were older and more disabled, however 39% had low
      disability scores. SD was a common problem for both men and women. Patients with
      RRMS were affected less in all items of primary SD. Several items of secondary SD
      -problems with memory and concentration, bladder symptoms, bowel symptoms--showed
      correlation with different items of primary SD; these were altered genital
      sensation, decreased libido, increased time for arousal, decreased
      lubrication/difficulties with erection. Total MSISQ-19 scores were correlated
      with disease duration, age, disability, disease course, Beck depression scale,
      temporary and long-standing anxiety and low level of education. CONCLUSION: SD is
      an underestimated, common symptom of MS. It may occur in MS even in the absence
      of severe disability. Physicians' awareness of this problem may help to bring
      about appropriate treatments and management, and improve the quality of life for
      these patients.

PMID- 16629426
TI  - Anorectal dysfunction in multiple sclerosis.
AB  - OBJECTIVE: To ascertain the prevalence of anorectal dysfunction (ARD) in patients
      with multiple sclerosis (MS) and its relationship with MS clinical
      characteristics. METHODS: Prospective transversal study in 193 patients with MS.
      All patients fulfilled a protocol that included: demographic variables, clinical
      characteristics of MS and the presence of ARD and urinary dysfunction (UD).
      RESULTS: One hundred and ninety-three patients: 66.8% women, an average age of
      42.8 (12.1) years; 67.8% of patients had relapsing remitting MS, 21.2% a
      secondary progressive and 10.9% a primary progressive form. The average duration
      of MS was 10.7 (9.4) years and the EDSS 2.8 (2.3). ARD was present in 93 patients
      (48.2%), and UD in 50.2%. ARD associated to UD was present in 35.7% of cases. The
      univariate study revealed that patients with ARD were older (P <0.001), had
      greater disability (P <0.0001), longer disease duration (P <0.001) and a greater
      association with UD (P<0.0001). ARD was more frequent in progressive forms
      (P<0.0001). The logistic regression analysis showed that female sex (P = 0.015),
      EDSS (P = 0.002) and UD (P = 0.003) were independent factors related to ARD.
      CONCLUSION: ARD is a highly prevalent disorder in MS. Female sex, EDSS and UD are
      independent predictors of ARD development.

PMID- 16629427
TI  - De-stabilizing and training effects of foot orthoses in multiple sclerosis.
AB  - This study evaluates the effects of dynamic foot orthoses (DFO) on walking and
      balance performance in people with multiple sclerosis (MS). Sixteen ambulant
      subjects with MS and ten age-matched healthy control subjects were studied on
      initial receipt of foot orthoses and after four weeks of daily wear. Walking
      speed, MS Walking Scale-12 (MSWS-12) and standing balance were assessed with and
      without orthoses at both these times. During standing, stance width and vision
      were varied, and performance was quantified using the velocity of the centre of
      pressure (COP), body sway velocity and the mean COP position relative to the
      shoe. People with MS walked slower (P <0.001) and showed increased sway when
      standing (P <0.001). At the first assessment, the foot orthoses caused an
      increase in sway and a medial and posterior shift of the COP position. At repeat
      measurement, the DFOs continued to increase sway compared to a shoe only
      condition. However, MS subjects reported an improvement in the MSWS-12 (P <0.05)
      and, compared to the initial session, showed decreased sway when eyes were closed
      both with and without DFOs. Dynamic foot orthoses may increase sway and change
      COP position by altering foot alignment and/or plantar afferent stimulation.
      Improvement in body sway over time may be an overall training effect of the DFOs,
      as MS subjects adapt to the initial de-stabilization.

PMID- 16629428
TI  - Comparison of the influence of different rehabilitation programmes on clinical,
      spirometric and spiroergometric parameters in patients with multiple sclerosis.
AB  - PURPOSE: The aim of this study was to compare the effect of four different
      programmes on spiroergometric, spirometric and clinical parameters in multiple
      sclerosis (MS) patients. METHODS: One hundred and twelve MS patients were divided
      into four groups. The first group underwent neurophysiologically based
      physiotherapy, the second aerobic training, the third combined therapy
      (neurophysiologically based physiotherapy and aerobic training) and the fourth
      did not change any habits. Seventeen patients did not finish the study. Patients
      were examined on impairment (Expanded Disability Status Scale), disability
      (Barthel Index), handicap (Environment Status Scale), quality of life (Multiple
      Sclerosis Quality of Life), fatigue (Modified Fatigue Impact Scale), depression
      (Beck Depression Inventory Score), respiratory function (spirometric parameters
      on spirometry) and physical fitness (spiroergometric parameters on a bicycle
      ergometer). RESULTS: The patients who participated in one of our training
      programmes showed a significant improvement of the examined parameters in
      comparison to those who did not change their present habits. Each of the four
      training programmes had a different impact on the parameters, which means that
      each of them had a different effect. The neurophysiologically based physiotherapy
      had the greatest impact on impairment, and the aerobic training on spirometric
      and spiroergometric parameters. All methods (the neurophysiologically based
      physiotherapy, the aerobic training and the combined programme) had an impact on
      fatigue.

PMID- 16629429
TI  - The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis
      patients.
AB  - OBJECTIVE: To evaluate the short-term efficacy of multidisciplinary, inpatient
      rehabilitation of multiple sclerosis (MS) patients. METHODS: A double-blind,
      randomized, parallel group design was used. The intervention group were offered
      comprehensive, multidisciplinary inpatient rehabilitation at the Haslev MS
      Hospital for an average of 35.5 days, while the control group received no
      treatment related to the study. All patients were examined in their homes twice
      with a 10-week interval. The rehabilitation of the intervention group started 2-3
      weeks after the first examination and ended 2-3 weeks before the second
      examination. Impairment was assessed by the Multiple Sclerosis Impairment Scale
      and the Expanded Disability Status Scale. Disability was assessed by means of
      Guy's Neurological Disability Scale. Two specific scales were used to assess
      upper limb function and ambulation: The Nine-Hole Peg Test and timed 10-metre
      walking. Patients' own perception of bodily pain, bladder symptoms, spasticity,
      fatigue, impaired walking and transfers were recorded using visual analogue
      scales. Finally, quality of life was assessed using the Life Appreciation and
      Satisfaction Questionnaire and the Functional Assessment in Multiple Sclerosis.
      PATIENTS: Two hundred and thirty-three patients were screened and of those 38
      were included for treatment and 52 as controls. RESULTS: We found no
      statistically significant differences between the two groups in any of the
      outcome measures. CONCLUSION: Although the study was underpowered, the negative
      outcome exposes the difficulties in quantitative analyses of the efficacy of
      multidisciplinary rehabilitation, which is liable to confounding factors such as
      variation in the indication for treatment, in the placebo effect, and in the
      reliability and responsiveness of the outcome measures.

PMID- 16629430
TI  - Gastroparesis with multiple sclerosis.
AB  - Symptomatology in multiple sclerosis (MS) depends on the areas of demyelination
      which can be situated anywhere in the white matter of central nervous system
      (CNS). Upper gastrointestinal tract symptoms are rarely reported. We recently saw
      a patient with MS who had disabling gastroparesis and dysphagia.

PMID- 16629431
TI  - Preventing adolescents from adopting HIV-related risky sexual behaviours: do we
      have all the answers?

PMID- 16629432
TI  - Health risk behaviours, awareness, treatment and control of hypertension among
      rural community people in Thailand.
AB  - This cross-sectional study aimed to assess health risk behaviours, prevalence,
      awareness, treatment, and control of hypertension and associated factors among
      Thai rural community people. 527 people, aged 35-60 years, were randomly sampled
      and interviewed. Two blood pressure (BP) measurements were assessed by
      standardized protocol. Hypertension was defined as a mean systolic BP > or = 140
      mmHg or diastolic BP > or = 90 mmHg. 76.9% lacked regular exercise, 28.5% were
      current alcohol drinkers, and 23.7% were current smokers. The prevalence of
      hypertension was 17.8%. Among the hypertensive cases, 64.9% (61/94) were aware of
      their high BP, 42.6% (26/61) were treated, and 42.3% (11/26) achieved BP control
      (< 140/ 90 mmHg). Multiple logistic regression analysis indicated four variables
      significantly associated with hypertension: age > 40 years (adjusted OR = 4.20,
      95% CI 1.93-9.11), married status (adjusted OR = 0.48, 95% CI 0.26-0.89), family
      history of hypertension (adjusted OR = 2.39, 95% CI 1.40-4.07), and BMI > 23.0
      kg/m2 (adjusted OR = 3.41, 95% CI 1.80-6.45). Lifestyle modification programs are
      needed to prevent hypertension.

PMID- 16629433
TI  - Why do patients with chronic illnesses fail to keep their appointments? A
      telephone interview.
AB  - Missed appointments affect patients' health in addition to reducing practice
      efficiency. This study explored the rate and reasons of non-attendance among
      patients with chronic illnesses. It was a cross-sectional descriptive study
      carried out in a family practice clinic over a one-month period in 2004. Those
      who failed turn up for scheduled appointments were interviewed by telephone based
      on a structured questionnaire. Out of 671 patients, the non-attendance rate was
      16.7%. Sixty-seven percent of non-attenders were successfully interviewed. Males
      (p = 0.01), Indians (p = 0.015), patients with coronary artery disease (p =
      0.017), multiple diseases (> 4) (p = 0.036) and shorter appointment intervals (p
      = 0.001) were more likely to default. The main reasons for non-attendance were:
      forgot the appointment dates (32.9%), not feeling well (12.3%), administrative
      errors (19.1%) and work or family commitments (8.2%). The majority would prefer a
      reminder through telephone (71.4%), followed by letters (41.3%). In conclusion,
      appropriate intervention could be taken based on the reasons identified in this
      study.

PMID- 16629434
TI  - Colorectal cancer screening with faecal occult blood testing: community
      intention, knowledge, beliefs and behaviour.
AB  - The objective of this study was to examine the current community intention,
      knowledge, beliefs and behaviour regarding colorectal cancer (CRC) screening with
      faecal occult blood testing (FOBT). A cross sectional telephone survey of the
      general population was conducted in Queensland, Australia. A random sample of
      1,136 residents aged 40-80 years were invited to participate in the survey with a
      response rate of 77.8%. 77.5% (95% confidence interval [95% CI]: 74.0 to 80.7%)
      of respondents reported that they would participate in CRC screening by FOBT if
      recommended to do so by doctors or health authorities. Screening intention was
      significantly associated with interest in further information concerning CRC or
      CRC screening (odds ratio: 6.7; 95% CI: 3.4 - 13.1), belief that CRC screening is
      necessary for persons without symptoms (5.0; 95% CI: 1.5 -17.1), and belief that
      treating bowel cancer in the early stages increases a person's chance of survival
      (5.1; 95% CI: 2.6 - 9.9). Knowledge of seeking medical advice (2.8; 95% CI: 0.9 -
      8.7) and diarrhoea/constipation as a symptom of CRC (1.7; 95% CI: 0.9 - 3.2),
      self-initiated screening behaviour (1.5; 95% CI: 0.8 -2.9), and medical check a
      couple of times a year or more (2.4; 95% CI: 0.9 - 6.5) were also marginally
      significantly associated with screening intention. Community intention to screen
      for CRC with FOBT may have increased over recent years. Screening intention is
      associated with community knowledge, attitudes/beliefs and behaviour.

PMID- 16629435
TI  - Screening results of anaemia among infants in a village in Okinawa, Japan: a
      cross-sectional study.
AB  - The aim of this study is to highlight the baseline characteristics of the results
      of a screening test for anaemia among infants in a village in Okinawa, Japan. The
      groups were classified into two; infants with and without anaemia. A total of 201
      infants were screened at 3-4 months, 9-10 months and 18 months. The study showed
      that gestational age and BMI were predictive of anaemia at 3-4 months of age. At
      9-10 months, types of feeding and weight ratio were the only factors that were
      found to be significantly predictive of anaemia. However, no factor was found to
      be predictive of anaemia at 18 months. Anaemia cases were found to occur at 3-4
      months and 9-10 months. Most of the anaemia cases have successfully undergone
      treatment.

PMID- 16629436
TI  - Improving immunization coverage through budgeted microplans and sub-national
      performance agreements: early experience from Cambodia.
AB  - In recent years, Cambodia has demonstrated significant success in specific
      aspects of immunization with gains through campaign efforts in measles control
      and polio eradication. In contrast, routine immunization rates have failed to
      improve over the last five years. In response, the National Immunization Program
      of the Ministry of Health developed a coverage improvement planning (CIP)
      process. This paper describes the CIP process in Cambodia, including identified
      barriers to and strategies for improving coverage. Immunization coverage rose in
      8 of 10 pilot districts in the year following the introduction of CIP in 2003.
      The mean increase in DPT3 coverage across pilot districts on an annual basis was
      16%, which provides encouraging early evidence for the effectiveness of the
      intervention. Factors associated with success in coverage improvement included:
      (1) development of a needs-based micro-plan, (2) application of performance-based
      contracting between levels of management, (3) investment in social mobilization,
      (4) securing finance for health outreach programs and (5) strengthened monitoring
      systems. Lessons learned will guide program expansion to improve immunization
      coverage nationally.

PMID- 16629437
TI  - Targeting antiretroviral therapy: lessons from a longitudinal study of morbidity
      and treatment in relation to CD4 count in Thailand.
AB  - The aim of the study was to quantify the incidence of illness and treatment
      behaviour in relation to CD4 count, age, and gender among a cohort of persons
      living with HIV/AIDS in Thailand. 464 participants with a CD4 count between 50
      and 550 cells/mm3 were followed up for 12 months. Multiple Poisson regression was
      used to model the adjusted incidence rate ratio of illness and care seeking at
      different levels. The incidence of morbidity and treatment pattern were
      significantly different among participants with different CD4 count, age and
      gender. For example, morbidity incidence was significantly higher among
      participants with CD4 count of less than 200 cells/mm3, among female
      participants, and participants aged 35 years or over. Females made significantly
      higher use of hospital ambulatory care and private clinics than males and males
      made significantly more use of private pharmacies. The potential opportunity cost
      of not providing ART to these different groups can be estimated and used to
      inform further economic evaluation and policy decisions on whether to provide ART
      at all and which patient groups to prioritise.

PMID- 16629438
TI  - Ethnicity as a determinant of asthma-related quality of life in a multiracial
      country.
AB  - In a multiracial country like Malaysia, ethnicity may influence the measurement
      of health-related quality of life (HRQL) in asthmatic patients. We invited 131
      adult patients [44 Malays, 42 Chinese and 45 Indians; mean (95% CI) age: 43 (40.2
      45.7) yrs; 28.2% male] with moderate-to-severe persistent asthma followed up in
      an urban-based hospital outpatient clinic to complete a disease-specific HRQL
      questionnaire [St Georges' Respiratory Questionnaire (SGRQ)] and to provide socio
      demographic and asthma-related data. Indians reported significantly worse SGRQ
      total score, compared to Malays [mean (95% CI) difference: 10.15 (0.51-19.78); p
      = 0.037] and SGRQ activity score, compared to Malays [13.50 (1.95-25.05); p =
      0.019] and Chinese [11.88 (0.19-25.05); p = 0.046]. Further analysis using
      multivariate linear regression showed that Indian ethnicity remained
      independently associated with SGRQ scores. Our finding highlights the relevance
      of ethnicity in assessing HRQL of asthmatic patients in a multiracial country
      such as Malaysia.

PMID- 16629439
TI  - Frequency and nature of falls among older women in India.
AB  - The purpose of this study was to examine the frequency and nature of falls and
      fall-related injuries among older women in the state of Kerala, India. The study
      involved 82 community living and 63 institutionalized women aged 60 years or
      older in Trivandrum, Kerala, India. Demographic data and falls profile were
      collected through the use of a field survey. A significantly lower percentage
      (45%) of community dwelling participants suffered a fall in the previous year,
      compared to 64% of those in the Long Term Care (LTC) settings (p < .05). Overall,
      of those who fell, 74% reported an injury (e.g., cuts and bruises, fractures) as
      a result of the fall, and 48% of older adults in the community and 70% in the LTC
      setting required medical treatment as a result of the falls. Falling is emerging
      as a significant public health problem facing older women in the state of Kerala.
      Fall prevention strategies to address falls should be explored and implemented
      within the Indian context.

PMID- 16629440
TI  - Active transport to work in Australia: is it all downhill from here?
AB  - Physical inactivity is increasing in Australia and active forms of transportation
      may be one way to increase the working population's daily physical activity. We
      used travel-to-work data from employed persons aged 15 years and over
      participating in the 1996 (n = 7,636,319) and 2001 (n = 8,298,606) Australian
      censuses to determine prevalence and trends in walking and cycling to work by
      state and gender, and differences in prevalence by age. In 2001, 3.8% of
      Australians walked to work and < 1% cycled. Over 64% travelled to work by car.
      There have been small declines in walking (men and women) and cycling (men) over
      the 5-years from 1996 to 2001. People were more likely to walk or cycle to work
      if they lived in the Northern Territory, if they were male or if they were aged
      15 to 24 years. They were more likely to travel by car if they lived in the
      Australian Capital Territory, if they were male, or if they were aged 45-54
      years. Few people walk or cycle to work in Australia. Efforts to encourage active
      transportation are urgently needed.

PMID- 16629441
TI  - Effect of time delay on survival in patients with non-small cell lung cancer--a
      Malaysian study.
AB  - The prognosis of lung cancer remains poor with overall five year survival figures
      varying between five and 10% worldwide, However, it has been shown that surgery
      in patients with early stage disease in non-small cell lung cancer can achieve
      five year survival rates up to 80%, suggesting that early or delay diagnosis can
      influence prognosis. Nevertheless, studies addressing this have been inconclusive
      and mostly derived from Western countries.

PMID- 16629442
TI  - [Neurological diseases and autoantibodies].

PMID- 16629443
TI  - [Echogenicity of the substantia nigra in Parkinson's disease: its relation to
      clinical findings].

PMID- 16629444
TI  - [Clinical usefulness of the frontal assessment battery (FAB) for elderly in
      memory clinic].
AB  - To investigate the usefulness of the frontal assessment battery (FAB) as a brief
      assessment for diagnosis in patients with dementia, we examined cognitive
      function using the FAB, Mini-mental state examination (MMSE), Kana-hiroi test,
      and Raven's colored progressive matrices (RCPM). Subjects were 82 senile patients
      having amnesia as a complaint including 28 Alzheimer's disease (AD), 14
      frontotemporal dementia (FTD), 17 vascular dementia (VD), 13 mild cognitive
      impairment (MCI), and 10 healthy persons. We discussed the difference of scores
      in different types of dementia. In the FAB, the scores of healthy persons and MCI
      were much higher compared with the scores of all types of dementia. There were
      high correlation between FAB and MMSE, Kana-hiroi test, and RCPM. Although some
      subjects showed normal score in MMSE and/or RCPM, they showed low score in FAB.
      Based on this, FAB is efficient for the differential diagnosis of dementia as
      brief screening tool.

PMID- 16629445
TI  - [Trends in the incidence of stroke in Yamagata, Japan].
AB  - The purpose of this study was to clarify the incidence and features of acute
      cerebrovascular diseases in Yamagata Prefecture, by comparing with those in other
      prefectures reported in previous studies. Consecutive 13,639 cases of acute
      stroke were prospectively registered to Yamagata Society in Treatment for
      Cerebral Stroke (YSTCS) between January 1, 1998 and December 31, 2002. Cerebral
      infarction (CI), intracerebral hemorrhage (CH), subarachnoid hemorrhage (SAH) and
      transient ischemic attack (TIA) were observed in 58.4%, 25.8%, 11.4% and 4.4% of
      the patients, respectively. The frequencies of CH and SAH (37.2%) in Yamagata
      Prefecture were higher than those reported in other studies (p < 0.01). In
      addition, time from onset to admission in Yamagata Prefecture was longer than
      that reported in others(p< 0.01). This study was one of the largest stroke
      registration studies in Japan enrolling 13,639 patients. In addition, computed
      tomography (CT) and/or magnetic resonance image (MRI) was performed on admission
      in all patients. Diagnosis was made by a neurologist or a neurosurgeon based on
      CT and/or MRI findings. Our results might accurately reflect current status of
      stroke patients in Yamagata Prefecture.

PMID- 16629446
TI  - [A survey about the accessibility to botulinum toxin therapy for dystonia].
AB  - We investigated the accessibility of the therapy with botulinum toxin for
      blepharospasm or cervical dystonia in Japan. Based on the administration sheet
      for Botox sent to the Japan Branch of Allergan Co. Ltd. (Tokyo, Japan), the
      survey was performed about how many institutions treated 3 or more patients with
      botulinum toxin in each of February, 2003, and February, 2005, for each disease
      entity. Among 369 secondary medical zones covering all the areas of Japan, 73
      zones had 103 institutions that met our criteria for blepharospasm in 2003, and
      the number slightly increased to 77 zones and 109 institutions in 2005. For
      cervical dystonia, 25 zones had 32 institutions in 2003, and the number increased
      to 36 zones and 48 institutions in 2005. Although medical zones with larger
      population tended to have more institutions, there was great inequality in the
      accessibility of patients among medical zones. Besides, the number of
      institutions was thought to be quite insufficient especially for cervical
      dystonia in most areas of Japan. Larger number of institutions in any region of
      Japan should be preferably able to treat focal dystonia with botulinum toxin in
      order to improve patients' accessibility, because this safe and effective therapy
      can be now regarded as the first line for both blepharospasm and cervical
      dystonia.

PMID- 16629447
TI  - [Serial MRI findings of intracranial tuberculomas: a case report and review of
      the literature].
AB  - Intracranial tuberculoma is an infectious disorder, occurring with or without
      tuberculous meningitis. Although intracranial tuberculoma is rare in developed
      countries, its frequency has increased in recent years in association with aging
      and immunocompromised hosts. Because of the low sensitivity of Mycobacterium
      tuberculosis cultures or of DNA detection from cerebrospinal fluid, diagnosis of
      intracranial tuberculoma is often difficult. Conventional magnetic resonance (MR)
      imaging of the tuberculoma yields variable results and is indistinct from other
      inflammatory lesions or brain tumors. We report the case of a 74-year-old woman
      with progressive neurologic deterioration. MR imaging of the brain showed
      multiple ring-like enhancing lesions in the supra- and infra-tentorial regions,
      mimicking multiple metastatic brain tumors. Diffusion-weighted imaging (DWI) of
      the brain showed homogeneous high signals in each lesion. A cavity in the lung
      suggested systemic involvement of tuberculosis. Despite extensive examination,
      tuberculosis could not be detected. Nevertheless, anti-tuberculosis treatment was
      administered. The patient's neurologic condition initially deteriorated for 4
      weeks, then gradually improved. MRI showed marked improvement of the lesions
      after anti-tuberculosis treatment. Whereas conventional MRI is not specific in
      such cases, DWI might be useful for early assessment of intracranial
      tuberculosis.

PMID- 16629448
TI  - [An autopsied case of a woman with rheumatoid arthritis attacked by multiple
      cerebral emboli].
AB  - A 45-year-old woman, who had had rheumatoid arthritis for 12 years, had three
      attacks of cerebral embolism over two months and died after the final attack.
      Intensive clinical laboratory investigations did not disclose any specific
      origins of emboli, but an autopsy revealed a nodule at the base of the aortic
      valve which was pathologically proved to be a rheumatoid nodule. The thrombi were
      present from the distal part of left internal carotid artery up to the proximal
      part of the left middle cerebral artery. They were rich in fiber, but poorly
      organized endothelial cell, raising the possibility that they originated from
      other parts and have recently reached there. On the top of the rheumatoid nodule,
      a thrombus was present. It was easily ablated and a small amount of fibrin stuck
      the nodule. Based on these results, we concluded that cerebral emboli were
      originally generated at the top of a rheumatoid nodule in the heart. In patients
      with RA, rheumatoid nodules are rarely seen in the heart. If present, they
      usually cause cardiac failure or atrioventricular block, and seldom result in
      cerebral infarction. This is the first case in which an autopsy proved rheumatoid
      nodule in the heart which had caused multiple cerebral emboli. We should consider
      the possibility of rheumatoid nodules in the heart as an origin of cerebral
      emboli in patients with rheumatoid arthritis.

PMID- 16629449
TI  - [A case of acute oropharyngeal palsy with nasal voice as main symptom].
AB  - We report a patient with acute oropharyngeal palsy following enteritis. A 19-year
      old woman developed increasing nasal voice over a few days. Neurological
      examination on day 7 of her course showed paretic dysarthria and mild weakness of
      neck flexion and quadriceps femoris muscle (Medical Research Council grade, 4+).
      Her palatal movement was diminished, whereas both palatal and pharyngeal reflex
      was normal. She could swallow water, although she had a slight amount of liquid
      reflux to her nose on swallowing. High titers of serum anti-Campylobacter jejuni,
      anti-GQ1b and anti-GT1a IgG antibodies were detected. Her symptoms improved
      gradually without any treatment, and disappeared by 40 days from neurological
      onset. Nasal voice with slight swallowing impairment as initial symptom has been
      rarely reported, but can occur in acute oropharyngeal palsy. Therefore,
      neurologists should take into account the possibility of Guillain-Barre syndrome
      and the regional variants in patients who show nasal voice during the initial
      stage.

PMID- 16629450
TI  - [A case of vertebral artery dissection with recurrent brain embolism].
AB  - We report a 63-year-old case of the vertebral artery dissection with recurrent
      brain embolisms. She was admitted to the hospital because she suffered a visual
      symptom. She was examined by magnetic resonance imaging (MRI) and diagnosed a
      left vertebral artery (VA) dissection. Digital subtraction angiography (DSA)
      revealed the string sign on the left VA supporting the evidence of dissection.
      However, after DSA, multiple brain embolic stroke was occurred. She was treated
      with anti-platelet drug (sodium ozagrel), then, recanalization of the pseudo
      lumen at the dissecting lesion was observed by MRI examination. Anti-platelet
      medicine (cilostazol) was taken for preventing reattack although the dissecting
      lesion was not closed. Following 4 weeks, brain embolisms were observed in the
      posterior circulation system. MRI revealed a dilated pseudo-lumen at the
      dissecting lesion with recurrent VA. This time, she was treated only with free
      radical scavenger (edarabone). After the occlusion of the dissected VA was
      observed, she started to take anti-platelet medicine again. It is generally
      accepted to use anti-platelet drug or anti-coagulant drug as a treatment of VA
      dissection causing brain ischemia. However, it should be assessed more carefully
      in cases showing recanalization of the pseudo-lumen as observed in this case.
      Surgical treatments should be taken into consideration at the early stage,
      especially for the cases presenting fragile dissecting lesions. Further study
      need to decide the effective treatment of the vertebral artery dissection.

PMID- 16629451
TI  - [A case of coexistence with cavernous angioma and focal cortical dysplasia].
AB  - There have recently been a number of new pathological findings of specimens from
      epileptic foci that have become widespread of surgical treatment. We reported a
      case with seizures resulting from brain lesions which pathologically demonstrated
      a coexistence with a cavernous angioma and a focal cortical dysplasia. A 24-year
      old man was admitted to our hospital because of generalized convulsion from 1
      year ago. Brain MRI revealed an enhanced mass lesion, in diameter 1.5 cm, with
      hemosiderin rim in the left temporal tip. Ictal EEG showed the initiation of the
      spike from the lateral side of the left temporal lobe. Because the epileptogenic
      focus was thought to be the lateral side in the left temporal lobe, anterolateral
      temporal resection was performed and subsequently total removal of the tumor was
      performed. He had no seizure after surgery. A light microscopic examination was
      performed on specimens stained with hematoxilin and eosin. We verified to be
      pathologically coexistent with a cavernous angioma and a focal cortical
      dysplasia. We also found unusual neurons that were accompanied by perineuronal
      glial satellitosis in the subcortical white matter, those were occasionally
      observed in epileptic foci and were thought to be a form of neuronal migration
      disorders.

PMID- 16629452
TI  - [Two cases of Duchenne muscular dystrophy complicated with dilated cardiomyopathy
      and cerebral infarction].
AB  - We report two cases of Duchenne muscular dystrophy (DMD) complicated with dilated
      cardiomyopathy (DCM), who were affected with cerebral infarction. Case 1 suddenly
      developed dysarthria and right facial weakness at age 21. Cranial CT study
      disclosed a low density area in the left basal ganglia and internal capsule. Case
      2 had a history of transient ischemic attack (TIA) at age 21. Five months after
      the TIA, he developed right hemiplegia and dysarthria, and a low density area in
      the corona radiate in left cerebral hemisphere was observed in cranial CT. These
      two cases showed the radiographic cardiomegaly with cardio thoracic ratio (CTR)
      of 72.8% and 66.6%, the decreased echocardiographic left ventricular ejection
      fraction below 20%, and the elevated titer of thrombin-anti-thrombin III complex
      (TAT) and D-dimer. The autopsy of Case 2 at age 26 disclosed the remarkable
      degeneration and fibrosis of myocardium and old ischemic lesion in the left
      cerebral frontal cortex. Despite the negative finding of the emboli in the left
      heart, cardiogenic cerebral infarction secondary to DCM was strongly suspected in
      both cases.

PMID- 16629453
TI  - [Aneurysms of the anterior communicating artery and subclavian artery in
      association with congenital absence of unilateral internal carotid artery].
AB  - We encountered a rare case of unilateral internal carotid arterial defect
      complicated with anterior communicating aneurysm and subclavian artery aneurysm.
      The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA
      revealed defects in the right internal carotid artery and the right carotid
      canal, and an unruptured aneurysm in the anterior communicating artery. In
      addition, the patient was also found to have an unruptured aneurysm in the right
      subclavian artery. As both the aneurysms were considered to have a high risk of
      rupture and such subclavian aneurysms were likely to cause an embolism, radical
      surgery was performed for each aneurysm. The postoperative course was uneventful,
      and the patient was discharged without ambulatory limitations. Although the
      defect in the internal carotid artery is a relatively rare vascular deformity,
      the incidence of cerebral aneurysm is about 30% in such cases due to the marked
      hemodynamic stress involved. On the other hand, there have been only two previous
      case reports of internal carotid arterial defect complicated with a subclavian
      aneurysm. Moreover, there have been no previous reports of internal carotid
      arterial defect complicated with both an intracranial aneurysm and a subclavian
      aneurysm, as observed in the present case. Thus, this case was very rare and is
      reported here.

PMID- 16629454
TI  - [MR images of symptomatic Schmorl's node].

PMID- 16629455
TI  - [Dissection of the vertebral arteries and Babinski-Nageotte syndrome].

PMID- 16629456
TI  - [Enigma harbors in PBC].

PMID- 16629457
TI  - [Non-surgical treatment for pancreatic cancer].

PMID- 16629458
TI  - [Recent advances in surgical treatment of pancreatic cancer].

PMID- 16629459
TI  - [Clinical evaluation of covered self-expandable metallic stent for unresectable
      malignant stomach pyloric region and duodenal obstruction].
AB  - We evaluated palliative treatment for unresectable malignant stomach pyloric
      region and the duodenal obstruction using covered self-expandable metallic stent
      (SEMS). Fifty-seven patients (26 stomach pyloric stenosis, 31 duodenal stenosis)
      were underwent palliative treatment using covered SEMS. The covered SEMS was
      Ultraflex stent for esophageal obstruction. The covered SEMS was successfully
      indwelled in the target region in 56 patients. The patients became able to ingest
      orally after a mean of 2 days, and 96% of the patients (54/56) became able to eat
      solid or semi-solid diets later. The SEMS obstruction by tumor ingrowth or
      hyperplasia was not occurred, so SEMS was maintenance-free. We concluded covered
      SEMS was useful palliative treatment because it prevented SEMS obstruction by
      tumor ingrowth or hyperplasia and it was maintenance-free.

PMID- 16629460
TI  - [A case report: an ileus caused by cecal volvulus and intersigmoidal hernia due
      to mesenterium commune].
AB  - A 33-year old woman was referred to our hospital because of gradually progressing
      abdominal pain and abdominal distension. A computed tomography demonstrated that
      distended cecum was located in the left retroperitoneal space. Barium enema
      revealed that the descending colon was positioned at the right side of the
      abdomen and transverse colon became severely tapered. Ceacal volvulus in addition
      to the internal herniation into the left retroperitoneal space was clinically
      diagnosed. The patient received an emergent operation. Operative findings showed
      that mesenterium commune, no fixation of the colon to the retroperitonium, and
      the internal herniation of terminal ileum to transverse colon into the sigmoid
      mesentery. Moreover, the cecal volvulus was diagnosed at the left retroperitoneal
      space. The mesenterium commune with internal herniation and cecal volvulus is
      extremely rare but one of important causes of acute abdomen.

PMID- 16629461
TI  - [A case of lung tuberculosis which also incidentally found intestinal
      tuberculosis by 18F-fluorodeoxyglucose-positron emission tomography].
AB  - A 60-year-old women presenting with an abnormal shadow on a chest X-ray film was
      admitted to our hospital in June 2004. Her CT scan of the chest showed a cavitary
      mass shadow in the left upper lobe. FDG-PET was performed to examine whether this
      shadow was the lung cancer or not, and incidentally it showed an additional
      accumulation of FDG in the ileocecal resion. The colonoscopy was then carried
      out. Luminal narrowing with circumferential ulcer in the ileocecal resion could
      be observed, and pathological findings of the biopsy specimen revealed
      epithelioid cell granulomas. Partial lobectomy of the left upper lung was also
      performed, and the histological examination revealed typical pulmonary
      tuberculosis. Since the antituberculosis therapy was effective to the ileocecal
      lesion, we assert that the ileocecal lesion was intestinal tuberculosis.

PMID- 16629462
TI  - [A case of AFP and PIVKA-II producing gastric carcinoma].
AB  - A 71-year-old man was admitted to our hospital with edema of the ambilateral
      crura and liver dysfunction. Serum levels of AFP and PIVKA-II were both
      abnormally high. An abdominal CT revealed many low density masses in both lobes
      of the liver. Endoscopic examination and gastric radiography showed a Type 1
      tumor in the fornix of the stomach. Biopsy specimen showed poorly differentiated
      adenocarcinoma. Immunohistochemical stains demonstrated the presence of AFP and
      PIVKA-II in tumor cells. A diagnosis of AFP and PIVKA-II producing gastric
      carcinoma with liver metastasis was made and the internal use of S-1 was started.
      The result of treatment was determined to be partial response. However, the
      condition of his entire body gradually worsened and he died of hepatic
      insufficiency.

PMID- 16629463
TI  - [A case of recurrent mediastinal pancreatic pseudocyst].
AB  - A 46-year-old man complaining right lateroabdominal pain and dysphagia was
      admitted our hospital. The CT examination revealed the low density area spreading
      through the mediastinum. The patient's condition improved with fast and
      antibiotics. He was discharged from the hospital, having an equivocal diagnosis.
      Seven months later, his symptoms relapsed and he was hospitalized again. Further
      evaluation confirmed that his disease was the mediastinal pancreatic pseudocyst
      occurred by a pancreatic stone. The pseudocyst resolved twice with conservative
      therapy, fast and intravenous injection of antibiotics. We consider it a rare
      case, because mediastinal pancreatic pseudocyst generally have the tendency of
      becoming severe. Finally the operation was performed for depriving the pancreatic
      stone, which was the cause of pancreatic pseudocyst.

PMID- 16629464
TI  - [A case of gastric arteriovenous malformation forming faded depression].
AB  - A 48-year-old man was referred to our hospital because of anemia. Upper
      gastrointestinal endoscopy showed discolored depressive lesion like gastric
      cancer, 30mm in diameter, in the greater curvature of the upper gastric body.
      During the endoscopic examination, pulsative bleeding from the lesion was
      occurred and we performed clipping hemostasis. We diagnosed a gastric
      arteriovenous malformation by endoscopic ultrasonograph and angiography. A
      pylorus preserving-gastrectomy was performed and Pathohistological examination
      revealed arterio-venous connection in the submucosal layer of the gastric wall.

PMID- 16629465
TI  - [Psychosomatic therapy in dental practice].

PMID- 16629466
TI  - [Assessment of gene associated with Streptococcus mutans biofilm formation].
AB  - Streptococcus mutans, the primary etiological agent of human dental caries and an
      obligate biofilm-forming bacterium, has developed a variety of mechanisms to
      colonize the tooth surface. Oral transmission of S. mutans through contact
      between mother and child is thought to be one of the risks of developing dental
      caries. In this study, I surveyed oral transmission frequency of S. mutans from
      mother to a 3-year-old child. In 19 (10.9%) of 174 mother-child pairs, S. mutans
      was isolated from both mother and chihld. The identities of genomic DNA from S.
      mutans in 5 (45.5%) of the 11 mother-child pairs were presented. Among those, the
      biofilms formed by S. mutans 3 c and 4 c, respectively, which had high and low
      ability of biofilm formation, were examined by confocal laser scanning microscopy
      (CLSM). Microscopic analysis revealed that the volume of biofilm formation in 3 c
      was higher than that in 4 c biofilm in the bottom. Furthermore, DNA microarrays
      were used to study the gene expression profiles of 3 c and 4 c biofilms. In this
      paper we describe that about 3.8% of genes showed differential expression; about
      2.2% of genes were activated and about 1.6% were repressed in 3 c biofilm
      compared with 4 c biofilm. The present study suggests that biofilm gene
      expression is strongly associated with differential biofilm formation. Our
      identification of biofilm-involved genes points to mechanisms of the virulence of
      S. mutans and provides a first foothold for studying the natural history of S.
      mutans infections in mother and child.

PMID- 16629467
TI  - [Effect of p-nitrophenyl-xyloside on the biosynthesis of proteoglycan in rat
      ovarian granulosa cells--analyses of glycosaminoglycan synthesis in the Golgi
      apparatus].
AB  - Biosynthesis of proteoglycans and glycosaminoglycans in the presence of p
      nitrophenyl-xyloside was studied using a primary rat ovarian granulosa cell
      culture system. Addition of p-nitrophenyl-xyloside into cell culture medium
      caused about a 700% increase of [35S]sulfate incorporation (ED50 at 0.03 mM) into
      macromolecules, which included free chondroitin sulfate chains initiated on
      xyloside and native proteoglycans. Free chondroitin sulfate chains initiated on
      xyloside were almost exclusively secreted into the medium. The molecular size of
      chondroitin sulfate chains decreased from 40,000 to 21,000 as the total
      [35S]sulfate incorporation was enhanced, suggesting that enhanced synthesis of
      chondroitin sulfate perturbed the normal mechanism of glycosaminoglycan chain
      termination. Biosynthesis of heparan sulfate proteoglycans was reduced by
      approximately 50%, likely due to competition at the level of UDP-sugar
      precursors. [35S]Sulfate incorporation was shut down by the addition of
      cycloheximide with an initial half time of approximately 2 hr in the presence of
      xyloside, while that in the absence of xyloside was about 20 min. The difference
      likely reflects the turnover rate of glycosaminoglycan synthesizing capacity as a
      whole. The turnover rate of glycosaminoglycan synthesizing capacity observed in
      ovarian granulosa cells was much shorter than that observed in chondrocytes,
      reflecting the relative dominance of proteoglycan biosynthetic activity in the
      total metabolic activity of the cells.

PMID- 16629468
TI  - [Observation of the ultrastructure of the tongue coating].
AB  - An observational study was conducted to clarify the morphological features of the
      fine structure of the tongue coating, which is one of the main causes of
      halitosis. Tongue specimens from cadavers, whom dental students had practiced on
      for anatomy class, were used as materials to observe the surface structure.
      Tongue coatings were obtained from patients who were referred to the Fresh Breath
      Clinic, Dental Hospital, Tokyo Medical and Dental University. After macroscopic
      observation of the tongue surface, tongue coating and examination of halitosis,
      the tongue coating was scraped carefully, following which it was observed using a
      light microscope and transmission electron microscope (TEM). The results obtained
      were as follows. The tongue coating consisted mainly of bacteria and desquamated
      keratinized epithelium which originated chiefly from the filiform papilla. The
      desquamated keratinized epithelium was also composed of degenerated epithelium of
      every level, from a comparatively normal epithelium to a fragmented altered
      epithelium. In addition, the level of degeneration of the keratinized epithelium
      differed according to the state of distribution and the revitalization of
      bacteria located in its surroundings. The intensity of halitosis increased with
      the amount of tongue coating. Increased amounts of tongue coating, however, did
      not necessarily correlate with increased halitosis in the patients. It was
      suggested that the severity of halitosis was probably associated with the level
      of bacterial invasion-related degeneration of the desquamated keratinized
      epithelium (tongue coating's quality).

PMID- 16629469
TI  - [Treatment results of acupuncture in inferior alveolar and lingual nerves sensory
      paralysis after oral surgery].
AB  - The effect of acupuncture in sensory paralysis was evaluated in 43 patients.
      Thiry-two cases in the study group were after mandibular third molar extraction
      and 11 cases by postoperative injury of orthognathic surgery. Treatment was
      performed in four forms: needles only (A), A with moxibustion (AK), electrical
      needle stimulation (ESA) using LEP 4000 OhmPulser Ra direct current 6 V 5-100 Hz,
      and ESA+A; exercise therapy was also given 1 or 2 times weekly. There were,
      however, some variations depending on the patient's conditions. Visual analog
      scale (VAS) measurement was carried out in addition to the estimation of
      effectiveness. The group receiving ESA+A seemed to improve better than those
      receiving other forms of treatment. The results indicated that young patients
      less than 40 years old tend to improve with fewer treatment times of shorter
      duration. With respect to the relationship between the effect and the time of
      starting treatment, we noticed that the earlier the treatment is started, the
      better the improvement. In summary, the study indicated that acupuncture is
      useful in treating sensory paralysis.

PMID- 16629470
TI  - [Identification of the novel host factor that interacts with HIV-1 integrase and
      analysis of the expression profile of the interactor in vivo].
AB  - Human immunodeficiency virus type 1 (HIV-1) is one of the lentiviruses, and
      unlike other retroviruses, HIV-1 is capable of infecting not only dividing cells
      but also non-dividing cells. It has been strongly suggested that this property is
      due to the viral mechanism which facilitates the integration of the viral genome
      cDNA into the host chromosome more efficiently than other retroviruses. HIV-1
      integrase (IN) is a viral protein which catalyzes insertion of the viral genome
      cDNA into the host cell chromosome. However, it has been suggested that HIV-1 IN
      also plays putative roles at the steps prior to integration such as uncoating,
      reverse transcription and nuclear transport of the viral cDNA. In this study, we
      tried to identify the novel host factor which interacted with HIV-1 IN using two
      different kinds of yeast two hybrid methods: the conventional yeast two hybrid
      method and the mating method. First, the full-length cDNA fragment of HIV-1 IN
      was amplified using polymerase chain reaction (PCR), and the amplified products
      were ligated into pGBT 9 vector as bait. Plasmid vectors expressing human
      lymphocytes cDNA library and HeLa cDNA library were used as prey plasmid in the
      conventional yeast two hybrid method and the mating method, respectively. These
      plasmids were transformed into the corresponding yeast strain cells, and several
      positive clones were isolated. As a result, a known gene product was identified
      as a candidate. Further analysis revealed that this protein was expressed in
      HeLa, 293 T cells, primary macrophages and activated T lymphocytes, and that
      suppression of this protein expression affected HIV-1 replication.

PMID- 16629471
TI  - [Supporting independent oral health care among the home-care elderly--the
      influence of dementia].
AB  - The purpose of this study was to clarify the effects of dementia based on the
      changes of independence conditions targeting the home-care elderly classified as
      Care level 1 of care needs or support. The care managers entered the basic
      information and assessment including oral health care for them. The independence
      level and other aspects of the elderly with and without dementia were examined
      comparatively for eight weeks. The results were as follows: 1. The highest
      independence level was observed for oral health care of the elderly without
      dementia, and it remained at the highest level for eight weeks. 2. Almost all
      independence levels of the elderly with dementia were significantly lower than
      those without dementia. 3. The willingness of the elderly without dementia was
      high among all areas, it was the highest of oral health care. A significant
      difference was observed between those with and without dementia. 4. As for
      cooperation from family members, the lowest value was oral health care. It is
      suggested that the elderly requiring home-based long-term light care or support
      have a high independence level concerning oral health care. The willingness
      toward oral health care of the elderly with mild dementia was still high. The
      elderly with dementia were less independent regarding oral health care. Moreover,
      an increasing number of elderly people live by themselves, and do not expect
      support from their families. Active intervention by experts is necessary to
      improve their independence concerning oral health care.

PMID- 16629472
TI  - [The expression of transcription factor Osterix in human periodontal ligament
      cells].
AB  - Periodontal ligament (PDL) has a heterogeneous cell population, where some of the
      cells may be capable of differentiating into either cementoblasts or osteoblasts.
      Recently, C 2 H 2 zinc finger transcription factor Osterix has been reported.
      Osterix is one of the master regulators of bone cell differentiation and it has
      two different isoforms. According to a recent report, osteogenic differentiation
      of murine embryonic stem cells can be induced by overexpression of Osterix. The
      purpose of this study was to investigate about the expression of Osterix on human
      PDL (hPDL), and whether the osteogenic differentiation of hPDL cells can be
      induced by overexpression of Osterix. hPDL cells were obtained from healthy human
      teeth indicated for extraction for orthodontic treatment. All procedure used in
      this study was approved by the local ethical committee of Tokyo Medical and
      Dental University. To investigate expression of Osterix mRNA in hPDL tissues and
      cells, RT-PCR experiments were performed. Two different isoform Osterix
      expression vectors were made and transiently transfected into hPDL cells.
      Osteogenic differentiation was assessed by RT-PCR for genes associated with the
      osteoblast lineage such as Osteopontin, Osteocalcin, and Bone Sialoprotein. RT
      PCR analyses showed that osterix mRNA was expressed in both hPDL tissue and
      cells. The expression of Osterix short isoform was higher than that of the long
      isoform. Overexpression of Osterix induced upregulated expression of Bone
      Sialoprotein mRNA. In expression levels of Osteopontin and Osteocalcin mRNA,
      compared to the control, no difference was observed. In conclusion, Osterix plays
      important roles in the osteoblastic differentiation in hPDL cells and modulates
      the mineralization.

PMID- 16629473
TI  - [Quantitative analysis of periodontal pathogens in aggressive periodontitis
      patients in a Japanese population].
AB  - The aim of the present study was to clarify the relationship between the
      relative/absolute numbers of periodontal bacteria and different types of
      periodontitis. Fifteen patients with localized aggressive periodontitis (LAgP),
      25 patients with generalized aggressive periodontitis (GAgP) and 28 patients with
      chronic periodontitis (CP) were included in this study. Saliva and subgingival
      plaque samples were collected from all subjects for microbiological analysis. The
      prevalence and proportions of Actinobacillus actinomycetemcomitans, Tannerella
      forsythensis, Porphyromonas gingivalis and Treponema denticola were determined by
      conventional PCR and real-time PCR. The prevalence of A. actinomycetemcomitans in
      saliva was significantly higher in LAgP patients (46.7%) and GAgP patients
      (40.0%) than that in CP patients (14.3%). The mean proportion of A.
      actinomycetemcomitans in LAgP patients (4.42%) was significantly higher than that
      in GAgP patients (0.59%) and CP patients (0.37%) in saliva. In subgingival
      plaque, LAgP patients showed a significantly higher mean proportion of T.
      forsythensis (19.8%) than CP patients (7.45%). In conclusion, A.
      actinomycetemcomitans was the more predominant periodontopathic bacteria in LAgP
      than in GAgP and CP. The increased proportion of T. forsythensis might relate to
      LAgP, in addition to A. actinomycetemcomitans. These results indicate that real
      time PCR analysis is useful for the evaluation of the bacterial profiles in
      different types of periodontitis.

PMID- 16629474
TI  - [The relationship between three-dimensional occlusal force and tooth displacement
      depending on clenching force in function].
AB  - This study evaluated the relationship between occlusal force and tooth
      displacement in function. The three-dimensional tooth displacement transducer
      Type M-3 was used to measure the tooth displacement path and a three-dimensional
      small occlusal force sensor was developed to detect the occlusal force. Subjects'
      teeth were the upper and lower first molars. The three-dimensional tooth
      displacement and occlusal force of the upper and lower first molars were measured
      at the same time during light and heavy clenching in vivo. The direction of the
      tooth displacement and that of the occlusal force of the upper first molar almost
      coincided and they were along the palato-apical direction. However, in the lower
      first molar, the direction of occlusal force was in the apical direction, and the
      tooth displacement path was along the lingual direction. There was no
      relationship between the direction of occlusal force and clenching intensity at
      the upper and lower first molars and no relationship was observed between the
      direction of tooth displacement and occlusal force at the lower first molar.
      However, the upper molars showed a tendency to move more in the palatal direction
      as the force increased. In the case of the upper first molar, the energy of force
      seemed to change with the distortion of the alveolar bone especially around the
      root surface. However, in the case of the lower first molar, the energy of this
      occlusal force might be absorbed by the deformation of the mandible.

PMID- 16629475
TI  - [Studies on measurement of oral mucosal color with non-contact spectrum
      colorimeter].
AB  - Color inspection plays an important role in the diagnosis of oral mucosal
      lesions. However, it is sometimes difficult to diagnose by color, because color
      is always evaluated subjectively. In order to measure color objectively and
      quantitatively, we decided to use a newly developed spectrum colorimeter for the
      oral mucosa. To keep the same angle and distance, a special stick was utilized.
      Various experiments were performed and suitable conditions for accurate
      colorimetric measurement were decided, including room temperature with cooling
      fan, onset time of the device, calibration timing, and the angle between light
      and the measured surface. The reproducibility of this method was confirmed by
      measuring the color of the buccal mucosa in healthy persons.

PMID- 16629476
TI  - [Prediction of occult cervical lymph node metastasis in patients with stage I -II
      squamous cell carcinoma of the oral cavity].
AB  - The presence of lymph node metastasis is the most important prognostic factor in
      oral cancer. The purpose of this study was to find useful markers for predicting
      occult cervical lymph node metastasis in patients with stage I or II squamous
      cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors
      and 2 genetic markers to predict late or occult cervical metastasis in 33
      patients with stage I and II oral squamous cell carcinoma who underwent partial
      glossectomy through the mouth without elective neck dissection. In this study, we
      performed fluorescence in situ hybridization (FISH) with specimens obtained by
      fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material,
      to investigate numerical aberration of the gene. Late cervical lymph node
      metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after
      treatment of the primary tumor. Factors significantly associated with the
      development of cervical metastasis were the mode of invasion (p = 0.009), cyclin
      D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease
      free survival from metastatic disease was significantly lower in patients with
      mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in
      patients with cyclin D 1 or EGFR gene numerical aberrations than in those without
      such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our
      results indicate that patients with stage I - II squamous cell carcinoma of the
      oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene
      numerical aberration should be considered a high-risk group for late cervical
      lymph node metastasis.

PMID- 16629477
TI  - [Relationship between occlusal condition and the changes of bolus property during
      mastication].
AB  - The purpose of this study was to clarify the relationship between occlusal
      condition and changes of bolus property during mastication. The methods and
      results were as follows. Subjects were selected according to the classification
      of anterior-posterior occlusal condition of the first molars (Angle' Class I, II,
      III group). 1. Evaluation of the relationship between occlusal condition and
      subjective chewing difficulty based on a questionnaire survey using a visual
      analog scale (VAS): Class II and Class III groups showed significantly higher
      subjective chewing difficulty compared to the Class I group. 2. Evaluation of the
      relationship between occlusal condition and changes of bolus property (chewiness)
      during mastication: In the Class II and Class III groups, the decrease in
      chewiness during the initial phase of mastication was significantly low compared
      to that in the Class I group. 3. To verify the results of 2, we examined bolus
      destruction for different loading directions using FEM and evaluated the
      differences among the three groups. We also investigated the correlation of the
      actual jaw movement and the masticatory efficiency according to the loading
      direction in the three groups: In the Class II and III groups, actual jaw
      movement was not significantly correlated with the most efficient loading
      direction in bolus destruction compared to that in the Class I group. These
      results indicate the correlation between occlusal condition and changes of bolus
      property during mastication. The subjective chewing difficulty may be one
      mediating factor. The efficiency of bolus destruction during mastication may also
      be associated with the relationship between occlusal condition and bolus
      property.

PMID- 16629478
TI  - [Relationship between jaws and the masseter muscle by superimposing MR images on
      the cephalogram].
AB  - The purpose of this study was to observe the morphological relationship between
      maxillofacial skeleton and masseter by superimposing the masseter image
      constructed by MR image scanning on the cephalogram. Sixteen subjects with
      different mandibular plane angle were examined in this study. Cephalogram and MR
      images of each subject were taken, and the images were input to a computer by
      using a digitizer. The areas of masseter were selected in each MR scan image
      which were projected to the mid-sagittal layer of the MR scan images. The
      synthesized image of cephalogram and masseter was obtained by completely
      superimposing sagittal images of the masseter with the mid-sagittal-plane MR
      image on the cephalogram. The inclination of masseter was determined by the
      center of gravity on the cross-section of masseter. These synthesized images of
      cephalogram and masseter showed various shapes of masseter according to different
      mandibular plane angle. The inclination of masseter had a close correlation with
      some skeletal parameters (mandibular plane angle, ANB, Y-axis, facial angle,
      saddle angle) of cephalometric analysis. The volume of the masseter also had a
      close correlation with skeletal parameters (mandibular plane angle, gonial angle,
      Y-axis). These results revealed that morphometric analysis using synthesized
      images of cephalogram and masseter is useful, and that the inclination and the
      volume of masseter may have an influence on the shape of the mandibular bone and
      its vertical and anteroposterior development.

PMID- 16629479
TI  - [Quantitative analysis of characteristic variations of the facial features of
      Crouzon syndrome].
AB  - OBJECTIVES: The purpose of this study was 1) to obtain polygon data and
      individual parameters from facial photographs of Crouzon syndrome patients and
      general patients with malocclusion in order to synthesize facial images using a 3
      D wire frame model, and 2) to distinguish between Crouzon syndrome patients and
      general patients with malocclusion using quantitative analysis of characteristic
      variations of facial features. MATERIALS AND METHODS: The face images were
      prepared from standardized full-face photographs of 10 Crouzon patients (Crouzon
      group) and 10 general patients with malocclusion (General group). These facial
      images were fitted to the 3 D wire frame model and the polygon data were
      obtained. Following application of principal component analysis, the individual
      parameters of the standard face were considered to be individual feature
      parameters. Linear discriminant analysis using the individual feature parameters
      was applied to distinguish both groups, and the validity of this statistical
      method was estimated. Moreover, the discriminant rates of the parts of the face
      were calculated and compared to those of the full face. RESULTS: A discriminant
      rate of 90% was obtained. The application of individual feature parameters to
      facial features could be used to objectively distinguish between these two
      groups. The discriminant rates of the part of the face were lower than those of
      the full face. CONCLUSION: This method seemed to be effective for diagnosing
      congenital anomalies from facial features. Further research on other congenital
      anomalies would be necessary to apply this analysis as a new diagnostic step.

PMID- 16629480
TI  - [Remote facilitation of soleus H-reflex induced by clenching on occlusal
      stabilization appliances].

PMID- 16629481
TI  - [Myelodysplastic syndromes: approaches to these difficult to understand].

PMID- 16629482
TI  - [Aplastic anemia and pure red cell aplasia: diagnosis and treatment].

PMID- 16629483
TI  - [Regulation of mRNA stability by cytokines and its implications in apoptosis of
      hematopoietic cells and leukemogenesis].

PMID- 16629484
TI  - [Molecular pathogenesis of multiple myeloma].

PMID- 16629485
TI  - [Effective combined modality therapy for a patient with primary adrenal
      lymphoma].
AB  - Primary adrenal lymphoma is a rare lymphoma with clinical features consisting of
      a high incidence of bilateral adrenal involvement, diffuse large B-cell histology
      and secondary adrenal insufficiency. We report a successful treatment of a
      patient with primary adrenal lymphoma using a combined modality therapy (CMT). A
      62-year-old man was hospitalized with pain of the flank, and a computed
      tomography (CT) scan of the abdomen revealed very large, bilateral adrenal
      masses. A needle biopsy of the left adrenal mass revealed diffuse large B-cell
      lymphoma. After irradiation of both adrenal lymphomas and CHOP therapy
      accompanied by intrathecal treatment and rituximab, the patient underwent a left
      adrenalectomy and high-dose chemotherapy with autologous peripheral blood stem
      cell transplantation. The patient has been disease-free for 2 years after the
      diagnosis of primary adrenal lymphoma. In contrast to the previous reports of
      poor response to conventional-dose chemotherapy alone and short-term survival of
      patients with primary adrenal lymphoma, our patient has demonstrated that
      radiation therapy combined with chemotherapy and rituximab may be an effective
      modality as a first-line therapeutic regimen for localized primary adrenal
      lymphoma.

PMID- 16629486
TI  - [Acyclovir combined with plasma exchange for disseminated varicella-zoster virus
      infection after bone marrow transplantation].
AB  - In 2001, a 45-year-old man with severe aplastic anemia received a bone marrow
      transplantation from his HLA-identical sister, 2.5 years after which he developed
      severe liver dysfunction together with abdominal pain, disturbance of
      consciousness and generalized vesicles. Disseminated varicella-zoster virus
      infection was diagnosed by the detection of VZV DNA. Acyclovir and plasma
      exchange rapidly controlled his VZV-related symptoms and signs. Disseminated VZV
      infection is often fatal, but acyclovir and plasma exchange may be useful for
      such infection by reducing the circulating viral load.

PMID- 16629487
TI  - [Influenza surveillance in Japan].

PMID- 16629488
TI  - [Control and measure of zoonoses].
AB  - A world trend such as the free trade agreement (FTA) promoted by the World Trade
      Organization ( WTO) results in an expansion of both importation and exportation
      of industrial materials, grain, food products and domestic animals, as well as
      pets and wild animals. Nowadays not only foods but also various kinds of animals
      are arrived from all over the world to Japan, and an increase in the risk for
      invasion of zoonoses from abroad to Japan has been pointed out for many years.
      Actually, BSE, O-157, highly pathogenic avian influenza (HPAI) etc., invaded into
      Japan within recent several years, and a possibility of the outbreak of rabies,
      plaque or tularemia which might be introduced by imported animals is still high.
      In this article, I discuss the risk for zoonoses from the following points. They
      are "from animal to human, background of the world wide expansion of zoonoses, a
      warning to human being from nature, zoonosis control strategy, and future
      problems on zoonosis to be dissolved".

PMID- 16629489
TI  - [Clinicoradiological diagnosis of respiratory infections: estimate of pathogens
      by radiological findings and the strategy for treatment].
AB  - This review discusses the clinicoradiological findings of community-acquired
      respiratory infections and the treatment strategy for respiratory infections. To
      make a differential diagnosis between bacterial pneumonia, pneumonia caused by
      atypical pathogens, and mycobacterial infections, it is very important to analyze
      the radiological findings of inflammatory lung diseases based on normal antomical
      structures. If clinicoradiological anlyses could make these differentiations, the
      appropriate treatment strategy for respiratory infections could be established.
      To accomplish this, exact orientations of pulmonary lobulus, acinus, and
      respiratory bronchioles is very important. Then, through analyzing chest CT
      findings and distribution patterns based on normal anatomical structures,
      estimation of causative pathogens could be possible. Especially, whether
      inflammatory exudates could pass Kohn's pores as well as Lambert's channel or not
      is very important factor to affect radiological findings of several pneumonia (as
      traditionally called "segmental" and "nonsegmental" distribution). To
      differentiate infections caused by Mycobacterium tuberculosis from nontuberculous
      mycobacteria, several important criteria have been demonstrated. Briefly, it has
      been suggested that Mycobacterium avium complex (MAC) respiratory infection is
      increasing especially in elderly women without underlying diseases. In MAC
      respiratory infection, right middle lobe and left lingula are frequently involved
      and centrilobular nodules and diffuse bronchiectases are characteristic
      radiological findings. Finally, the role of telithromycin in the treatment of
      respiratory infections is discussed.

PMID- 16629490
TI  - [Topics on anaerobic bacteria and anaerobic infection].
AB  - Considerable information has been accumulated in the field of anaerobic bacteria
      and anaerobic infections in the last ten years. Here we tried to briefly
      introduce several selected topics of clinical importance in this field: Proposal
      of the term "Nanaerobe", Changes of classification and nomenclature of anaerobes,
      Anaerobic bacteremia, Lemierre's syndrome as a revival anaerobic infection,
      Atopobium vaginae as Bacterial Vaginosis-associated bacteria, and new actions of
      the Clostridium perfringens toxins.

PMID- 16629491
TI  - [Serum anti-lPS antibody production in an outbreak of enterohemorrhagic
      Escherichia coli O157 infection among schoolchildren].
AB  - Although there have been many reports of the usefulness of serodiagnosis of
      enterohemorrhagic Escherichia coli (EHEC) O157, the serotype of the bacteria
      detected and the increase in anti-LPS antibody have not always been consistent.
      In this study we investigated the diagnostic significance of measurements of anti
      LPS antibody by ELISA in an outbreak of O157 infection among schoolchildren in
      whom the bacteriological test findings were clarified and the age groups were
      uniform. The anti-LPS antibody titer was measured in 31 patients (77 serum
      samples) in an outbreak of EHEC O157 : H7 infection (220 children infected) that
      occurred in a primary school in Morioka in 1996. The anti-O157 LPS antibody
      positivity rates of IgM, IgG, and IgA were 98.7%, 85.7%, and 98.7%, respectively.
      Between the time the meal that caused the outbreak and 19 days later, anti-O157
      LPS IgM antibody and IgA antibody were detected in all patients. The specificity
      was investigated using control serum, and the specificity of IgM, IgG, and IgA
      was 93.5%, 93.5%, and 97.2%, respectively. Some samples contained antibodies
      against O111 and O26 LPS, but the titers were lower than the anti-O157 antibody
      titer. The anti-O111 antibody titer and anti-O26 antibody titer were highly
      correlated, suggesting that they were crossreactive antibodies for O157 LPS. No
      significant correlation was found between differences in clinical manifestations
      and the anti-O157 LPS antibody titer in this O157 outbreak in schoolchildren. It
      was clarified that an increase in anti-LPS antibody was found to support the
      diagnosis of mild cases of 0157 infection infection as well as severe cases.

PMID- 16629492
TI  - [Serotype distribution and penicillin-binding protein genes of Streptococcus
      pneumoniae in children with invasive pneumococcal infection].
AB  - Between August 1998 and July 2005, we studied the serotypes and mutation of
      penicillin-binding protein (PBP) genes of 46 strains of Streptococcus pneumoniae
      isolated from children with invasive pneumococcal infection in Hokkaido. The
      clinical diagnosis was pneumonia in 16 cases, occult bacteremia in 15, meningitis
      in 8, upper respiratory infection in 6, and arthritis in 1. Patients ranged in
      age from 2 months to 9 years old. Prevalent serotypes were 6B (39.1%), 23F
      (17.4%) 6A (8.7%), and 19F (8.7%). The serotype coverage rate by the 7-valent
      pneumococcal vaccine was greater than 70% in children. Mutation of 3 genes
      (Penicillin-binding S. pneumoniae, PRSP) was detected in 18 isolates, mutation of
      10 genes (pbp1a and pbp2x, or pbp2x and pbp2b) in 2, and of pbp2x alone in 15.
      PRSP was found in serotypes 6A, 6B, and 23F, and the rate of PRSP in 6A, 6B, and
      23F was 75.0%, 62.5%, and 55.6%, respectively.

PMID- 16629493
TI  - [Nosocomial infection by multidrug-resistant Pseudomonas Aeruginosa (MDRP)
      presumably spread a radiation technician].
AB  - Isolated of multidrug resistance Pseudomonas aeruginosa (MDRP) that the
      receptivity pattern of the antimicrobial suscepti respectively resembled isolated
      from clinical specimens (sputum) in two patients of each internal medicine ward
      in Kitasato University East Hospital for two days from September 18 and 20, 2004.
      Both of bacteria were formed small colonies of a smooth-type on dollargalluskey
      improvement-type BTB agar plates, and the judgment of ClassB (metallo)-beta
      lactamase by biochemical properties and disk diffusion method sodium mercaoto
      acetic acid (SMA) was mutually corresponding. Moreover, it was same serotype C
      according to the serotype, and it was confirmed that it was the same bacterial
      strain from the molecular epidemiology analysis by Random amplified polymorphic
      DNA polymerase chain reaction (Random amplified polymorphic DNA polymerase chain
      reaction: RAPD). From the investigation of clinical backgrounds of two patients
      who isolated bacterial strains, September 18, 2004. 10 : 20 a.m., and 10 : 40
      a.m., other chances that can become with contact infection in this hospital,
      except conducted X-Ray or roentgenograph of the chest and abdomen of Portable X
      ray device continuously done by one radiation technician was not seen. Because it
      had turned out that a radiation technician who had taken charge had been
      neglecting the hand washing at the time of each X-Ray or roentgenograph, it was
      guessed the case with nosocomial infection by contact infection occurred via
      specific radiation technician.

PMID- 16629494
TI  - [A study on measles epidemic in Sukagawa area, Fukushima Prefecture from 2002 to
      2003].
AB  - Measles epidemic occurred in southern part of Fukushima Prefecture from April
      2002 to July 2003. Public Iwase hospital in Sukagawa City was the central
      hospital in the measles epidemic area and 382 patients with measles were admitted
      to the hospital during the epidemic. Based on clinical records, age distribution,
      vaccination history, familiar infection and complications were retrospectively
      investigated. Moreover, the vaccination rates and their calculating methods in
      the area were compared and the problems on immunization against measles were
      discussed. As the result, we found that 1) measles epidemic centered on
      unvaccinated infants, 2) measles was still serious disease with many
      complications and sometimes fatal, 3) measles was highly infectious and there was
      no way for prevention except vaccination, 4) the actual condition of measles
      vaccination was not reflected exactly by the current calculating methods used for
      the local health reports by the Ministry of Health Labour and Welfare. For the
      prevention of measles epidemic, it is necessary to know the exact numbers of
      patients infected with measles and patients deceased due to measles, to calculate
      precise vaccination rate, and to form the consensus among parents, physicians and
      administrators to control measles epidemic by the vaccination.

PMID- 16629495
TI  - [Local reactions after diphtheria-tetanus-acellular pertussis vaccines in mice;
      changes in histopathology at the injection site].
AB  - Diphtheria-tetanus-acellular pertussis vaccine (DTaP) developed in Japan is now
      widely used worldwide. DTaP is safer than the diphtheria-tetanus-whole-cell
      pertussis vaccine (DTwP) and has fewer severe side effects, but local reactions
      such as redness, swelling, and induration are still reported. The
      pathophysiological mechanism of these reactions is controversial. To clarify the
      cause of local reactions, we conducted studies using the mouse model. After
      administering either one or two abdominal subcutaneous DTaP inoculations, we
      observed changes in histopathology at the injection site at 24h, 48h, and 7 days.
      The control group, inoculated with physiologic saline, showed no significant
      changes either pathologically or with the naked eye. All mice after DTaP
      vaccination showed indurations at the injection site. Pathologically, we watched
      leukocyte invasion into or around the site, especially neutrophils and
      eosinophils. After the first vaccination, the extent of the invasion was strong
      24h and 7 days later. At 24h following the second vaccination, a dramatic
      leukocyte invasion seen persisted at 7days. At 7 days after the first
      vaccination, peripheral fibrosis had begun, and when a second vaccination was
      administered, it began even earlier at the second site. These histopathological
      changes show that local reactions are caused by both inflammatory and allergic
      responses. Because this mouse study resulted in the same pattern of reactions
      observed in humans, this method will be useful for studies focusing on local
      reactions.

PMID- 16629496
TI  - [Successful treatment of invasive sinus aspergillosis with micafungin and
      itraconazole].
AB  - BACKGROUND: We report a case of invasive sinus aspergillosis that extended to the
      orbital cavity and cavernous sinus and was improved by treatment with micafungin
      and itraconazole. CASE REPORT: A 83-year-old woman was referred to our hospital
      because of headache and impaired of eye movement on the right side. Physical
      examination revealed impaired function of cranial nerves, II, II, IV, and VI on
      the right side. MRI showed evidence of inflammation of the right sphenoid sinus
      and ethmoidal sinus and an enhancing mass in the right cavernous sinus and orbit.
      Because a culture of a specimen from the right sphenoid sinus extracted during
      endoscopic sinus surgery, yielede Aspergillus fumigatus, a diagnosed of invasive
      sinus aspergillosis complicated by cavernous sinus symdrome and orbital apex
      symdrome was made. It was difficult to completely remove the mass in the sinuses
      surgically and drug therapy with micafungin was started and then itraconazole was
      added. The clinical manifestations and the impaired function of cranial nerves
      II, III, IV, and VI improved, and MRI showed regression of the mass in the
      sinuses temporary in response to drug therapy. CONCLUSION: Invasive sinus
      aspergillosis often progresses rapidly in the absence of surgery. Our case is
      valuable, because invasive sinus aspergillosis was improved by drug therapy
      alone, and combined treatment with micafungin and itraconazole was effective.

PMID- 16629497
TI  - [A case of anaphylactoid purpura associated with tuberculous pleuritis].
AB  - A 46-year-old man was admitted to Shin-Kokura Hospital because of fever and right
      chest pain. Laboratory studies showed mild leukocytosis, an increased erythrocyte
      sediment rate, positive C-reactive protein, and abnormal liver function. The
      tuberculin skin test was positive. A chest X-ray showed massive right pleural
      effusion, and exudative pleural effusion fluid was obtained by thoracocentesis.
      The pleural fluid revealed an increased adenosine deaminase concentration and
      cultures were negative for mycobacteria. A polymerase chain reaction test of the
      pleural effusion for Mycobacterium tuberculosis was positive. The patient was
      diagnosed with tuberculous pleuritis, and antitubercular therapy was started. The
      fever and chest pain was improved, but rashes appeared on the lower extremities.
      A biopsy of the skin lesion showed anaphylactoid purpura. Steroid ointment
      improved the skin lesion. Anaphylactoid purpura associated with tuberculosis is
      rare. The immunological response to mycobacteria may heve been related to the
      mechanism of the anaphylactoid purpura in this case.

PMID- 16629498
TI  - [Enterohemorrhagic Escherichia coli possessing the stx1 & stx2vha genes tended to
      produce low titers of shiga toxin production].

PMID- 16629499
TI  - Motivating HIV positive women to adhere to antiretroviral therapy and risk
      reduction behavior: the KHARMA Project.
AB  - Women comprise the fastest growing group of persons with AIDS. They are often
      diagnosed later in the disease, when antiretroviral therapy (ART) is strongly
      indicated. Antiretroviral therapy has transformed the course of HIV/AIDS to a
      treatable, chronic illness. This article provides a profile of women with
      HIV/AIDS and describes ART. Selected research related to adherence and motivation
      is summarized. Psychosocial and economic concerns specific to women, ART,
      adherence, and motivation are presented. The article reviews challenges for risk
      reduction behaviors for HIV+ women, such as sexual activity and substance abuse.
      The authors discuss the Keeping Health and Active with Risk reduction and
      Medication Adherence (KHARMA) Project, a research project in progress that was
      designed to promote adherence to both ART and risk reduction behaviors in HIV+
      women. The study includes two groups: a motivational group intervention based on
      motivational interviewing and a health promotion program control group tailored
      to the needs of HIV+ women. A description of the tailored intervention and
      project update is included.

PMID- 16629500
TI  - Health Insurance Portability and Accountability Act of 1996: just an incremental
      step in reshaping government.
AB  - In 1996, the federal Health Insurance Portability and Accountability Act (HIPAA)
      was adopted as a step toward reshaping government health care. Referred to as the
      HIPAA, it enables portability of health care insurance coverage for workers and
      their families when they change or lose their jobs (Title I), sets a standard or
      benchmark for safeguarding electronic and paper exchange of health information,
      and requires national identifiers for providers, health plans, and employers
      (Title II). The final policy implementation rule outlines the entities affected
      by the legislation as health care providers, health plans, health care
      clearinghouses, and vendors offering computer software applications to providers
      and those billing for health services (Health Privacy Project, 2002; Public Law
      104-191 1996; Rules and Regulations, 2003; U.S. Department of Labor, 2005). Aside
      from the federal law, some entities and even states have set standards more
      stringent than those promulgated by the federal mandate (U.S. Department of
      Health and Human Services 2004; 2005a).

PMID- 16629503
TI  - Emerging infectious diseases at the beginning of the 21st century.
AB  - The emergence and re-emergence of infectious diseases involves many interrelated
      factors. Global interconnectedness continues to increase with international
      travel and trade; economic, political, and cultural interactions; and human-to
      human and animal-to-human interactions. These interactions include the accidental
      and deliberate sharing of microbial agents and antimicrobial resistance and allow
      the emergence of new and unrecognized microbial disease agents. As the 21st
      century begins, already new agents have been identified, and new outbreaks have
      occurred. Solutions to limiting the spread of emerging infectious diseases will
      require cooperative efforts among many disciplines and entities worldwide. This
      article defines emerging infectious diseases, summarizes historical background,
      and discusses factors that contribute to emergence. Seven agents that have made a
      significant appearance, particularly in the 21st century, are reviewed,
      including: Ebola and Marburg hemorrhagic fevers, human monkeypox, bovine
      spongiform encephalopathy, severe acute respiratory syndrome (SARS), West Nile
      virus, and avian influenza. The article provides for each agent a brief
      historical background, case descriptions, and health care implications.

PMID- 16629504
TI  - Early detection and surveillance for biopreparedness and emerging infectious
      diseases.
AB  - Biological weapons and emerging infectious diseases pose a significant risk to
      public health. A timely response is needed to effectively treat and contain a
      potential infectious disease outbreak. Detection and surveillance of biological
      agents needs to be sensitive and specific to allow providers to quickly and
      accurately identify the disease process and begin the necessary response
      procedures. This article addresses the importance of early detection and
      surveillance of both intentional and unintentional biological events. Challenges
      of bioterrorism and the nursing role in response are discussed. Epidemiological
      considerations, such as route of transmission and personal protective equipment,
      are presented. An overview of the major surveillance systems, including advances
      in computer-based technology, is provided to help health care providers become
      aware of current surveillance systems and clinical decision support tools
      designed to help diminish the impact of biological threats.

PMID- 16629505
TI  - The impact of tuberculosis on Zambia and the Zambian nursing workforce.
AB  - In Zambia, the incidence of tuberculosis (TB) has greatly increased in the last
      10 years. This article describes Zambia and highlights the country's use of the
      United Nations Millennium Development Goals as a framework to guide TB treatment
      programmes. An overview of TB in Zambia is provided. Data related to TB cases at
      the county's main referral hospital, the University Teaching Hospital (UTH), is
      discussed. Treatment policies and barriers are described. Zambian nurses have
      been greatly affected by the rise in the morbidity and mortality of nurses with
      TB. This article explains the impact of TB on the Zambian nursing workforce.
      Review of Zambian government programmes designed to address this health crisis
      and targeted interventions to reduce TB among nurses are offered.

PMID- 16629506
TI  - The 2003 SARS outbreak: global challenges and innovative infection control
      measures.
AB  - In early 2003, the global infection control community faced a great challenge,
      sudden acute respiratory syndrome (SARS). The rapid spread of SARS, its capacity
      to infect health care workers, and its many unknown features in the early days of
      the outbreak meant that health care workers were unsure of the most effective
      methods of infection control to prevent disease transmission. These conditions
      made designing appropriate, effective and standard infection control responses
      difficult. Innovation was necessary. This article provides a brief overview of
      global challenges in infection control and SARS. The author reports field
      observations and describes five selected examples of highly innovative, SARS
      related infection control practices observed in three affected countries during
      the height of the 2003 outbreak. These examples relate to risk assessment,
      patient segregation, strategies to limit access to clinical areas, health care
      worker protection, and efforts to promote public confidence. Many of these
      strategies could be considered for use in the post-2003 SARS era, especially in
      preparation for an influenza or Avian influenza pandemic.

PMID- 16629507
TI  - Practical cancer prevention--where is it going to occur and who is going to be
      responsible?

PMID- 16629508
TI  - The JICA training course, community-based cancer prevention for the Asian Pacific
      countries, fiscal years 2004 and 2005 (epidemiological approach).
AB  - Communicable diseases are still major causes of deaths in developing countries.
      Cancer incidence, however, increased 19% between 1990 and 2000, mainly in this
      same developing world (Stewart and Kleihaus, 2003), and malignant neoplasms are
      now the second leading cause of mortality in these countries (WHO, 2003).
      Limitations of medical facilities and equipment mean that prevention is
      indispensable for cancer control (Mikheev et al., 1994). However, human resources
      concerning cancer prevention are limited, and encouragement of their development
      should be taken as a first priority. To assist in this aim, the present training
      course was designed by the Division of Epidemiology and Prevention, Aichi Cancer
      Center Research Institute, Japan, and has been annually conducted since 1999,
      supported by the Japan International Cooperation Agency (JICA) (Takezaki, 2001;
      2002; 2003; Wakai, 2004). The course targets doctors and public health workers
      who are responsible for community-based cancer prevention in developing countries
      to promote the introduction of comprehensive procedures, focusing mainly on
      primary prevention but also including screening for secondary prevention of
      cancer.

PMID- 16629509
TI  - Physical activity in the prevention of cancer.
AB  - OBJECTIVE: The purpose of this paper is to update epidemiological research on
      relations between physical activity and cancer risk, including physical activity
      measurement and potential mechanisms of prevention of cancer. DESIGN: Review of
      recent systematic reviews, meta-analyses and studies on the topic that have been
      published in the recent literature. RESULTS: Convincing epidemiological evidence
      exists that physical activity reduces colon and breast cancers. The evidence is
      weaker for prostate (classified as probable), lung and endometrial cancers
      (classified as possible), and insufficient for cancers at all other sites.
      Hypothesized biological mechanisms for the physical activity--cancer association
      include changes in hormone level, reduced percentage of body fat, enhancement of
      the immune system, and alteration in free radical damage by scavenger systems.
      The available data indicate that 30-60 minutes per day of moderate-to-vigorous
      physical activity is needed to be protective against breast and colon cancers.
      CONCLUSION: A greater understanding of the biological mechanisms operating in the
      physical activity--cancer relation, complete measurements of physical activity
      through a subject's life, assessment of all potential confounders and association
      modifiers are needed to confirm a protective role of physical activity in cancer
      development and allow specific exercise prescriptions for prevention in
      particular cancer sites.

PMID- 16629510
TI  - Biological activity of bee propolis in health and disease.
AB  - Propolis is a natural product derived from plant resins collected by honeybees.
      It is used by bees as glue, a general-purpose sealer, and as draught-extruder for
      beehives. Propolis has been used in folk medicine for centuries. It is known that
      propolis possesses anti-microbial, antioxidative, anti-ulcer and anti-tumor
      activities. Therefore, propolis has attracted much attention in recent years as a
      useful or potential substance used in medicine and cosmetics products.
      Furthermore, it is now extensively used in foods and beverages with the claim
      that it can maintain or improve human health. The chemical composition of
      propolis is quite complicated. More than 300 compounds such as polyphenols,
      phenolic aldehydes, sequiterpene quinines, coumarins, amino acids, steroids and
      inorganic compounds have been identified in propolis samples. The contents depend
      on the collecting location, time and plant source. Consequently, biological
      activities of propolis gathered from different phytogeographical areas and time
      periods vary greatly. In this review, the activity of bee propolis will be
      presented with special emphasis on the antitumor activity.

PMID- 16629511
TI  - Anticarcinogenic potential of lipids from Hippophae--evidence from the recent
      literature.
AB  - Hippophae (Sea buckthorn) is a deciduous species, widely distributed throughout
      the world. Its important products are whole berries, leaves, juice and oil. The
      last two give this plant a shining name and position in medicinal plants. They
      contain different kinds of nutrients and bioactive substances such as vitamins,
      carotenoids, flavonoids, polyunsaturated fatty acids, free amino acids and
      elemental components. The clinical trials and scientific studies during the 20th
      century confirm medicinal and nutritional value of sea buckthorn, and the most
      important of them is its anti-carcinogenic properties. This mini-review is
      focused on the anti-carcinogenic potential of lipids from this plant, in order to
      open up a clear understanding for further detailed study in this regard.

PMID- 16629512
TI  - Social inequalities in cancer with special reference to South Asian countries.
AB  - There are major differences in cancer burden across socioeconomic classes, as is
      evident from the data for cancer incidence and mortality from Greater Mumbai,
      India. Changes over time are also evident and recently there has been a clear
      shift to increasing breast cancer particularly in well-educated women, who
      conversely are at much lower risk of cervical cancer. With infection-related and
      tobacco-related cancers, programs of prevention and early detection will yield
      desirable results only if it is associated with a program directed towards
      elimination of poverty, illiteracy and restoring social inequality. Similarly
      education must play a role in combatting diet-related neoplasia but here the
      target population may differ, requiring a specific awareness of psychological
      profiles.

PMID- 16629513
TI  - Searching for cancer deaths in Australia: National Death Index vs. cancer
      registries.
AB  - OBJECTIVE: To compare the accuracy, costs and utility of using the National Death
      Index (NDI) and state-based cancer registries in determining the mortality status
      of a cohort of women diagnosed with ovarian cancer in the early 1990s. METHODS:
      As part of a large prognostic study, identifying information on 822 women
      diagnosed with ovarian cancer between 1990 and 1993, was simultaneously submitted
      to the NDI and three state-based cancer registries to identify deceased women as
      of June 30, 1999. This was compared to the gold standard of "definite deaths". A
      comparative evaluation was also made of the time and costs associated with the
      two methods. RESULTS: Of the 450 definite deaths in our cohort the NDI correctly
      identified 417 and all of the 372 women known to be alive (sensitivity 93%,
      specificity 100%). Inconsistencies in identifiers recorded in our cohort files,
      particularly names, were responsible for the majority of known deaths not
      matching with the NDI, and if eliminated would increase the sensitivity to 98%.
      The cancer registries correctly identified 431 of the 450 definite deaths
      (sensitivity 96%). The costs associated with the NDI search were the same as the
      cancer registry searches, but the cancer registries took two months longer to
      conduct the searches. CONCLUSIONS AND IMPLICATIONS: This study indicates that the
      cancer registries are valuable, cost effective agencies for follow-up of
      mortality outcome in cancer cohorts, particularly where cohort members were
      residents of those states. For following large national cohorts the NDI provides
      additional information and flexibility when searching for deaths in Australia.
      This study also shows that women can be followed up for mortality with a high
      degree of accuracy using either service. Because each service makes a valuable
      contribution to the identification of deceased cancer subjects, both should be
      considered for optimal mortality follow-up in studies of cancer patients.

PMID- 16629514
TI  - 5-year survival rates for primary cancer sites at cancer-treatment-oriented
      hospitals in Japan.
AB  - In Japan, The Japanese Association of Clinical Cancer Centers (JACCCs) was
      established in 1965 by systematizing cancer-treatment-oriented hospitals. The
      core center of JACCCs is the National Cancer Center in Tokyo. In 1984, JACCCs
      created The "Improvement for Clinical Cancer Centers in Japan" Study Group (The
      Study Group) which has subsequently routinely evaluated the effectiveness of the
      therapy that is provided. In general, the 5-year (relative) survival rate is
      employed as an indicator of the treatment efficacy. The present survey used the
      PC software program KAP developed by Chiba Cancer Center in Japan, to calculate 5
      year observed survival rates and the 5-year relative survival rates using Ederer
      II methods. The overall 5-year relative survival rates in patients with stomach
      (15,353 patients), colon (5,054), rectum (3,695), lung (10,153), breast (11,302)
      and cervix of the uterus (6,336) were 68.7%, 72.2%, 69.4%, 28.1%, 86.1% and
      81.1%, respectively. The survival rates discussed so far are principally observed
      survival rates. The 5-year relative survival rate for those institutions that
      specialize in cancer treatment should become an index for Japanese cancer
      treatment.

PMID- 16629515
TI  - Lifestyle factors and breast cancer: a case-control study in Kuala Lumpur,
      Malaysia.
AB  - Breast cancer is the most common female cancer and the commonest cause of death
      due to cancer for women in Malaysia. This study was performed to identify the
      relationship with lifestyle factors. A case-control study was conducted among
      females with breast cancer who came for treatment to the Breast Clinic Hospital
      Kuala Lumpur in July until September 2004. A total of 203 female patients were
      recruited as cases along with 203 patients who attended the Outpatient Clinic,
      Hospital Kuala Lumpur during the study period as the controls. The study showed
      women who did not exercise regularly to have four times higher risk (adjusted
      odds ratio is 3.49, 95% CI is 1.84 to 6.62) compared to those who exercised
      regularly. Women with a high fat diet were also at elevated risk (adjusted odds
      ratio 3.84, 95% CI is 1.20 to 12.34) compared to those consuming a low fat diet.
      Women without breast cancer generally had a longer duration of lifetime lactation
      with a median of thirty-three months compared to women with breast cancer (twenty
      months, p<0.05). Women who did not take oral contraceptive pills but had breast
      fed their child have a 56.0% lower risk (crude odds ratio 0.44, CI is 0.22 to
      0.87) compared to women who did not take oral contraceptive pill and also did not
      breast-feed their child. If they had breast fed for thirteen months and above,
      they faced a 61.0% lower risk (crude odds ratio 0.39, 95% CI is 0.17 to 0.87).
      There was a significant inverse trend for lifetime lactation and breast cancer
      risk. In conclusion certain life styles of women are associated with a higher
      risk of breast cancer development. Therefore, the promotion of a healthy life
      style should be emphasized.

PMID- 16629516
TI  - Health promotion for middle-aged Isan women, Thailand: a participatory approach.
AB  - It is increasingly clear that non-communicable diseases (NCDs), including cancer,
      diabetes, hypertension and atherosclerosis, are important not only for the
      developed but also the developing world. Prevention efforts depend on community
      based interventions and for these to be successful a participatory approach is
      necessary. The present paper describes experiences with middle-aged females
      living in a village in Isan, the Northeastern area of Thailand, focusing on the
      steps necessary to develop trust between researcher and subjects, the actual
      conditions of the women involved and their problems. From this base a number of
      interventions are planned taking into account the wishes of the villagers
      themselves, including a project to facilitate participation in physical exercise,
      a prime measure for prevention of cancer and other NCDs.

PMID- 16629517
TI  - Patho-epidemiology of lung cancer in Karachi (1995-2002).
AB  - The objective of the study was to provide an overview of the demographics of lung
      cancer, the number one cancer killer of men in Karachi South (1995-2002). Lung
      cancer cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st
      December 2004 were analyzed. To allow for maximum data completion, cases recorded
      from 1st January 1995 to 31st December 2002 were included for final analysis.
      Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2
      time periods, 1995-1997 and 1998-2002. Odds ratio for sex, age-groups, ethnicity,
      religion, and residence by socio-economic categories were calculated by
      considering all malignancies (except tobacco-associated malignancies) for each
      group, registered at KCR for the same period as controls. Cancer of the lung
      ranked the most frequent malignancy in men in Karachi in the entire 1995-2002
      period, though it did not feature amongst the first 10 malignancies in the
      females. In the 1995-1997 period, the ASR per 100,000 population for cancer of
      the lung was 21.4 and 2.9 in males (M) and females (F) respectively. The mean age
      of the patients was 60.4 years (95% CI, 59.1-61.7) M and 53.7 years (95% CI 48.9
      58.5) F. In the 1998-2002 period the incidence rate increased to 25.5 per 100,000
      (M) and 4.2 per 100,000 (F). Thus between 1995 and 2002, the incidence of lung
      cancer registered a 19% increase in men and almost 100% in women. The component
      of adenocarcinoma in females remained stable during 8 years, but increased 55% in
      males. Histologic confirmation was 80%; majority of cancer cases presented as
      grade 3 and grade 4 lesions (62.3%), and were discovered at advanced stages
      (stage III 35.7%; stage IV 55.8%). The odds ratio (OR) in men was 4.5 (95% CI
      3.7; 5.4). The risk of developing lung cancer increased with age, the highest
      risk being observed in the 65+ age group. A marginally higher risk was observed
      in the higher socio-economic categories for men and in the lower socio-economic
      categories for women. A higher risk was also observed for men who were residing
      along the coastal belt, and for ethnicities belonging to Southern Pakistan
      (Sindhi and Mohajir) residing in Karachi South. In conclusion, Pakistan at
      present falls into a low risk lung cancer region in females and a moderate risk
      region for males and the highest registered increase between 1995 and 2002 was
      observed in the older age groups (65+). It is however a cause of concern that the
      overall lung cancer incidence rates continue to rise. The age specific rates
      though stable in the younger age groups (35-49 years), are at present equivalent
      to contemporary rates in high- risk countries. These rates correspond with the
      trends of smoking prevalence in the younger age groups in the last 2 decades.
      Published studies have given alerts to increase in the smoking habits of the
      present day youngsters and with an expanding population the country can expect a
      substantial increase in lung cancer. This threat can only be averted by
      implementation of stringent anti-tobacco rules and health education; prohibition
      of smoking in educational institutions at all levels and a ban on the sale of
      cigarettes to minors.

PMID- 16629518
TI  - Distribution of cancer and adenomatous polyps in the colorectum: study in an
      Iranian population.
AB  - OBJECTIVE: There is consensus that the majority of colorectal carcinomas (CRCs)
      arise from adenomatous polyps. Therefore, for management of colorectal cancer,
      diagnosis and endoscopic resection of adenomas is advised. If the same etiologic
      factors are operating for polyps and cancers their anatomical distributions
      should be the same. The present study was conducted to determine whether the
      distribution of adenomas is consistent with that of CRCs and for comparison with
      other studies, especially in Western populations. MATERIALS AND METHODS: We
      reviewed, retrospectively , endoscopically reported anatomic sites of all
      adenomatous polyps and CRCs which were histologically confirmed from Jan 1992 to
      Dec 2005 in Tabriz, the North-west of Iran. One hundred and forty-three CRC's and
      180 adenomatous polyps (in 145 patients) were found. Patients with polyposis
      syndromes were excluded the analysis. Age and sex of patients, size and anatomic
      sites of polyps and cancers were studied. RESULTS: The average ages of patients
      with adenomas and cancers were 46.3(SD 14.7) and 53.9(SD 13.3)years, with 55.5%
      and 62.2% in males, respectively. In both cancer and adenoma cases the most
      common presenting symptoms were rectal bleeding and bloody diarrhea ( 52.4% ,
      16.9% and 39.2% , 15.8% for cancers and adenomas, respectively) without any
      significant difference(0>05). The vast majority of adenomas (85%) and cancers
      (81.7%) were left sided (p>0.05). The propensity for polyps to be found in the
      descending colon was of borderline significance (p=0.07). The cecal segment
      uniquely demonstrated cancers(p=0.01) without any polyps. CONCLUSION: A similar
      anatomic distribution pattern and left shift of colorectal adenomas and cancers
      in this Iranian population is compatible with most other Asian countries.
      However, because of the occurrence of the neoplasms in the right colon total
      colonoscopy should still be considered for screening purposes.

PMID- 16629519
TI  - Changes in incidence of in situ and invasive breast cancer by histology type
      following mammography screening.
AB  - OBJECTIVE: To investigate secular trends and correlates of incidence of breast
      cancer by histology type following the introduction of population-based
      mammography screening. METHODS: Analysis of age-standardised incidence rates for
      1,423 in situ and 16,157 invasive carcinomas recorded on the South Australian
      population-based cancer registry for the 1985-2004 diagnostic period. Multiple
      logistic regression was undertaken to compare socio-demographic characteristics
      by histology. Progression from in situ disease was investigated using the Kaplan
      Meier method. RESULTS: The incidence of in situ lesions increased approximately
      seven-fold over the 20-year period, compared with an increase of about 40% for
      invasive cancers. The increase for in situ lesions was due to increases for
      ductal carcinomas, with little change for lobular lesions. By comparison, the
      percentage increase in incidence for invasive cancer was greater for lobular than
      ductal cancers. Both for in situ and invasive cancers, percentage increases were
      greatest for the screening target age range of 50-69 years. One in 14 in situ
      cases was found to progress to invasive cancer within seven years of diagnosis,
      but insufficient detail was available to determine whether the invasive cancers
      were a progression of the in situ lesions or whether they originated separately.
      These invasive cancers were smaller than generally applying for other invasive
      cancers of the female breast. CONCLUSIONS: The larger secular increases in
      incidence for in situ than invasive cancers would reflect the dominant role of
      mammography in the detection of ductal carcinoma in situ. The lack of an increase
      for lobular in situ lesions may have resulted from their poorer radiological
      visibility. The greater percentage increase for lobular than ductal invasive
      lesions may have been due to an increase in imaging sensitivity for these
      lesions, plus real increases in incidence. The smaller sizes of invasive cancers
      found in women with a prior in situ diagnosis may have resulted from more
      intensive medical surveillance, although the possibility of biological
      differences cannot be discounted.

PMID- 16629520
TI  - Trends in incidence of childhood leukemia, Khon Kaen, Thailand, 1985-2002.
AB  - BACKGROUND: The Khon Kaen Cancer Registry (KKCR), providing both hospital and
      population-based registration, was established in 1984 in the Faculty of
      Medicine, Khon Kaen University. Leukemia is the most common cancer among Thai
      children in Thailand, including both curable and preventable types, but no
      assessment of trends has hitherto been performed. OBJECTIVE: To perform a
      statistical assessment of the incidence trend of childhood leukemia in Khon Kaen,
      Thailand, between 1985 and 2002. METHODS: Population-based cases of childhood
      leukemia registered between 1985 and 2002 were retrieved from the KKCR and cases
      with an ICD-O diagnosis (coding C42) in children under 15 were selected.
      Incidence trends were calculated using the Generalized Linear Model method (GLM),
      which generates incidence-rate-based logarithms. RESULTS: Of the 277 cases of
      leukemia, boys were affected two times more frequently than girls and half of the
      cases were 0-4 years of age. Most diagnoses were histologically- or cytologically
      proven and the most common type (affecting two-thirds, 65.7%) was acute
      lymphoblastic leukemia (ALL). The overall, age-standardized rate (ASR) for
      leukemia was 31.9 per million (95%CI: 28.1 to 35.7); 40.3 per million (95%CI:
      34.2 to 46.4) in boys and 27.0 (95%CI: 21.8 to 32.2) in girls. Incidence has been
      increasing by 2.4% per year in boys (95% CI: -0.5 to 5.3) and 4.1% per year in
      girls (95% CI: 1.1 to 7.2). CONCLUSIONS: This incidence-rate-based logarithm
      indicates that childhood leukemia has been increasing, suggesting further
      epidemiological research on causes and possible prevention is needed.

PMID- 16629521
TI  - Cancer screening, reproductive history, socioeconomic status, and anticipated
      cancer-related behavior among Hmong adults.
AB  - In the United States, breast, cervical, colorectal and prostate cancer screening
      rates are low or non-existent in the Hmong population compared to non-Hispanic
      Whites. No Hmong adults report ever participating in prostate (male only) and
      colorectal cancer screening. US-born Hmong women, those living in the US 20
      years, and those 39 years old are more likely to be screened for breast and
      cervical cancer than other women. The Hmong, in general, are a young population
      (median age = 34 years) with low socioeconomic status. As a function of these
      characteristics, 52% of Hmong women reported having their first child at 15-19
      years old and continued to bear children until 40-54 years old. The combination
      of young age at first pregnancy and multiparity probably protects Hmong women
      from breast cancer but elevates cervical cancer risk.

PMID- 16629522
TI  - Comparison of cancer incidence in Iran and Iranian immigrants to British
      Columbia, Canada.
AB  - Migrant studies provided strong evidence about the role of environment and life
      style in cancer risk. Iran has experienced many immigrants to other countries
      with different cultures and environment. This study compares cancer incidence
      rates in Iran, Iranian immigrants to British Columbia (BC), Canada, and the BC
      general population. Cancer incidence rates were computed from two population
      based cancer registries in Iran and from the BC cancer registry. A listing of
      common Iranian surnames and given names was produced to identify Iranian
      immigrants within the BC cancer registry. Age-standardized rates (ASRs) were
      calculated using mid year census data. The overall cancer incidence rate for
      Iranian female immigrants was intermediate between rates for Iran and the BC
      general population, and the rate for Iranian male immigrants was lower as
      compared to the other population groups. For female Iranian immigrants, the
      incidence of breast cancer was increased four-fold, and for colorectal cancer two
      fold, as compared to Iranian rates. A dramatic decrease was found in the
      incidence of both stomach and oesophageal cancers for Iranian immigrants of both
      sexes. For male Iranian immigrants, the incidence of prostate cancer was
      increased as compared to Iranian rates. Differences in incidence rates of
      specific cancers were observed between BC Iranian immigrants and Iran, with
      cancer patterns in Iranian immigrants being more similar to the BC general
      population. This warrants further investigation into differences in lifestyle and
      cancer detection.

PMID- 16629523
TI  - Epstein-Barr virus-associated extranodal non-Hodgkin's lymphoma of the sinonasal
      tract and nasopharynx in Thailand.
AB  - Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of
      malignant lymphoma. In our previous report on nodal malignant lymphoma in
      Thailand, we found that 64% of classical Hodgkin's lymphoma (cHL), 51% of non
      Hodgkin's lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin's lymphoma, B-cell
      (NHL-B) were EBV-related. In the present research, we conducted a retrospective
      study of primary extranodal non-Hodgkin's lymphoma of the sinonasal tract (e-NHL
      ST) and primary extranodal non-Hodgkin's lymphoma of the nasopharynx (e-NHL-NP)
      in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by
      in situ hybridization was performed in all cases and a T-cell receptor (TCR)-g
      gene rearrangement study was performed in NHL-T cases. There were 18 cases of e
      NHL-ST and 42 cases of e-NHL-NP detected by histologic and immunohistochemistry
      examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal
      malignant lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e
      NHL-ST and 7 cases (16.7%) of e-NHL-NP were NHL-T, and the remainder were NHL-B.
      All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) of the NHL-B
      cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-gamma
      gene were detected in 71.4% of the extranodal NK/T-cell lymphomas, nasal type,
      patients; 50.0% of peripheral T-cell lymphoma, unspecified, patients; and one
      case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong
      association of NHL-T in the sinonasal tract or nasopharynx with EBV infection,
      the link apparently being weaker in NHL-B patients. The study also indicates that
      most cases of extranodal NK/T-cell lymphoma, nasal type, are not the germline
      configuration of the TCR genes.

PMID- 16629524
TI  - Chewing of betel, areca and tobacco: perceptions and knowledge regarding their
      role in head and neck cancers in an urban squatter settlement in Pakistan.
AB  - The link of betel, areca and chewable tobacco with head and neck cancers is
      clearly established. Fifty eight percent of the global head and neck cancers
      occur in South and Southeast Asia, where chewing of betel, areca and tobacco are
      common. This study was carried out to establish the pattern of use of Paan,
      Chaalia, Gutka, Niswar, Tumbaku and Naas among population of squatter settlement
      of Karachi and to determine the perceptions and knowledge regarding their role in
      the etiology of head and neck cancers. It was a cross-sectional study, performed
      at Bilal colony in Karachi. Through systematic sampling, 425 subjects [a male and
      female from a household] were interviewed with a structured questionnaire.
      Knowledge regarding etiology of head and neck cancers was classified in ordinals
      of "good", "some" and "poor", for each substance separately, while practices were
      classified into "daily user", "occasional user" and "never user". About 40% of
      the participants were chewing at least one item [betel, areca or tobacco
      products] on daily basis. This prevalence was 2.46 times higher among males than
      females and 1.39 times higher among adolescents than adults. At least 79% of the
      participants were classified as having poor knowledge about the carcinogenicity
      of each of these items. Knowledge increased with age and level of education.
      Health hazards of these items were poorly recognized and about 20% perceived at
      least one of these items to be beneficial. Positive attitudes were seen regarding
      the steps to curb the production, business and consumption of these substances.
      In conclusion, prevalence of chewing of betel, areca and tobacco among adults and
      adolescents is high. Deficiency in knowledge and wrong perception of favorable
      effect of chewing products is common. Besides curtailing the availability of
      chewing products, correct knowledge regarding its ill-effects should be
      inculcated among population to decrease the burden of head and neck cancers.

PMID- 16629525
TI  - Inhibition of rat urinary bladder carcinogenesis by the antiangiogenic drug TNP
      470.
AB  - Potential inhibitory effects of the antiangiogenic drug TNP-470 on rat urinary
      bladder carcinogenesis were investigated in F344 male rats initiated with 0.05%
      BBN in the drinking water for 8 weeks. Group 1 was then continuously treated with
      TNP-470 by subcutaneous injection using osmotic minipump until the end of the
      experiment; group 2 served as the control with only initiation. The incidences
      and multiplicities of papillomas and carcinomas in the TNP-470-treated group were
      significantly decreased compared to the control group values along with the tumor
      vascular density. In conclusion, TNP-470 can inhibit rat urinary bladder
      carcinogenesis, presumably through its effects on angiogenesis.

PMID- 16629526
TI  - Trends of head and neck cancers in urban and rural India.
AB  - BACKGROUND: The sub-site predilection of head and neck squamous cell carcinoma
      (HNSCC) reflects the risk profile of a community and there are suggestions that
      these are changing over time. OBJECTIVE: To determine the change in head and neck
      cancer in rural and urban populations in India. METHODS: Cancer registry data of
      an urban and a rural population were reviewed over a period of 13 and 11 years,
      respectively. Age adjusted rates (AAR) and age specific incidence rates were used
      for data analysis. RESULTS: Oral cancers formed the majority of the head and neck
      cancers with a predilection for tongue, except in rural males, in whom the
      pharynx was the predominant sub-site. Overall there was a reduction in the
      incidence of HNSCC, which was more pronounced in urban females and rural males
      (p< .001). Among the sub-sites, oral cavity cancers showed a decreasing trend in
      urban females (p< .01) and rural males (p< .01). However, the trend was towards
      increase of incidence of tongue cancers. Pharyngeal cancer showed reduction in
      urban females (p< .01), whereas it increased in rural females. The recent
      increase in incidence of young adults with HNSCC reported in developed countries
      was not observed. CONCLUSIONS: Overall, incidence of HNSCC is reducing. This may
      be attributed to the decreased prevalence of tobacco use. The increase in
      incidence of tongue cancer may suggest factors other than tobacco and alcohol in
      its genesis.

PMID- 16629527
TI  - Selected risk factors, human papillomavirus infection and the p53 codon 72
      polymorphism in patients with squamous intraepithelial lesions in northeastern
      Thailand.
AB  - Risk factors for cervical squamous intraepithelial lesions (SIL) including human
      papillomavirus (HPV) infection and the p53 codon 72 polymorphism were
      investigated in a case-control study with 103 cases and 105 controls in
      Northeastern Thailand. Increased risk for SIL was observed for age at menarche
      (odds ratio (OR) = 2.2; p< 0.005), age at the first sexual intercourse (OR=2.4;
      p< 0.05), number of sexual partners (OR=2.7; p< 0.005) and partners' smoking
      history (OR=2.3-3.2; p< 0.01). Prevalence of malignant type of HPV infection in
      the control and SIL groups was 18.1% and 60.2%, respectively. HPV infection
      significantly increased risk for SIL 6.8-fold (p< 0.001). HPV-16 infection was
      the commonest (31 out of 62 carriers) in SIL patients and highly associated with
      risk. The p53 codon 72 polymorphism was not identified as a genetic risk for SIL
      in this study, as demonstrated in Thai cervical cancer. Therefore, to prevent
      cervical neoplasia or HPV infection, inclusion of knowledge on sexual behavior
      and effects of smoking into public health programs is important and, at the same
      time, a nation-wide screening scheme for cervical abnormalities including HPV
      typing is a high priority in Thailand.

PMID- 16629528
TI  - Carcinoma of the male breast: a study of 141 cases from northern Pakistan.
AB  - Carcinoma of the male breast, histologically identical to that seen in females,
      is a rare malignant epithelial tumour. We retrospectively studied 141 cases of
      male breast carcinoma diagnosed during a ten year period (1992-2001). These
      tumours comprised 0.7% of all cancers, 1.1% of all malignancies in males and 5.9%
      of all breast carcinomas in both genders. A male to female ratio of 1:16 was
      observed. The peak incidence was in the age group between 50-60 years and
      majority of the patients were below 60 years. Most of the patients presented with
      a painless lump and infiltrating ductal carcinoma was the main histological type.
      While compared with our previous similar analysis, a highly significant increase
      (p< 0.0001) was found for total numbers of breast carcinoma in both sexes and
      total number of malignancies in males.

PMID- 16629529
TI  - Effects of cessation of alcohol exposure on rat hepatocarcinogenesis.
AB  - Cessation of long-term alcohol exposure is reported to enhance rat
      hepatocarcinogenesis. The purpose of the present study was to assess this
      possibility using glutathione-S transferase placental form (GST-P) positive foci
      as end point lesions. All rats were treated with a single i.p. injection of
      diethylnitrosamine (DEN) (200 mg/kg body weight) and then given a MF pellet diet
      for 2 weeks. Thereafter, the animals were maintained on: alcohol liquid diet in
      which 36% of total calories were provided by alcohol (5% Al diet) for 6 weeks
      (group 1); control liquid diet (C diet) for 6 weeks (group 2); 5% Al diet for 6
      weeks and subsequently C diet for 4 weeks (group 3); 5% Al diet for 10 weeks
      (group 4); or C diet for 10 weeks (group 5). All rats were subjected to two
      thirds partial hepatectomy at 3 weeks after DEN injection. The number and area of
      GST-P positive foci per cm2 of liver tissue were slightly increased in group 1
      compared to the group 2 and significantly elevated in the group 4 compared to
      group 5. However, numbers in group 3 were significantly lower in group 4 and
      similar to the group 5 values. PCNA positive cells in the GST-P positive foci in
      the group 1 and group 4 were significantly increased as compared with respective
      controls (groups 2 and 5, respectively), while indices in the group 3 were again
      similar to values for group 5. Cessation of short-term alcohol administration
      thus had no promoting effects on development of GST-P foci, suggesting that the
      duration of alcohol treatment may be important. The results also imply the
      existence of a cumulative exposure time or dose threshold for alcohol if
      promoting effects of cessation are to be seen on rat hepatocarcinogenesis.

PMID- 16629530
TI  - Cancer mortality in a Hanoi population, Viet Nam, 1996-2005.
AB  - BACKGROUND: Hitherto, cancer mortality data have not been available in Viet Nam,
      so that the real public health problem with this disease has yet to be addressed
      and recognized in the country with a population of over 80 million in South East
      Asia. The aim of the present pilot study was to examine cancer mortality in a
      commune population of Hanoi city, 1996-2005. METHODS: Cancer data was accessed
      from the database of the population-routine-based death registration performed by
      medical workers at commune health stations based on the guidelines of the
      Ministry of Health at Hanoi city. All deaths occurring in the community were
      registered. This registration process was monthly reviewed for each fatal case
      regarding the name, age, sex, address, occupation, date-place-cause of death, and
      information concerning to pre-death medical care during the study period from
      Jan. 1996 to Dec. 2005. The list of death and residents of the study population
      was carefully cross-checked with other information sources to avoid under- or
      over-registration. The world population structure was used to estimate age
      standardized cancer mortality rates per 100,000, (ASR). RESULTS: During 60,770
      person-years estimated from Jan. 1996 to Dec. 2005, 320 deaths and their causes
      were registered. Among them, 100 cancer cases of all sites (66 males and 34
      females) were included. Cancer mortality rates were 222 and 109 (Crude), 353 and
      115 (ASR), for males and females, respectively. For both genders combined, lung
      cancer was the most common, 27 cases, followed by liver, 26 cases and stomach,
      with 19. Proportion of death from cancer was about 31% of all causes.
      CONCLUSIONS: The present findings suggest that in Viet Nam, a developing country,
      cancer is indeed an important public health problem.

PMID- 16629531
TI  - A pilot study on inducement of smoking cessation by a simple 5A (asking, advice,
      assess, assist, and arrange) approach at outpatient clinics.
AB  - Asking smokers about their smoking status, followed by advice to quit smoking,
      assessing the intention to quit, assistance with cessation, and arrange of follow
      up (5A) is recommended for induction of smoking cessation. To obtain preliminary
      data on effects of "5A" , we investigated the smoking cessation rate with two
      modes in the phase I: 1) self-administered questionnaire and 2) doctor's
      interview at respiratory disease clinics of three general hospitals in Japan, and
      another mode in phase II: 3) doctor's interview with an additional pamphlet at
      one of the three hospitals. The interviews for smokers were conducted by doctors
      in charge of treatment. Subject smoking habits were followed up by postal surveys
      three months after the enrollment. In phase I, 359 outpatients were recruited and
      189 smokers responded, among whom 27 patients (7.5% of 359 outpatients) had quit
      smoking at the three months after the enrollment. The cessation rate of the self
      administered questionnaire group (8.4% of 238 smokers) did not differ
      significantly from that of doctors' interview group (5.8% of 121 smokers). Age
      and intention to quit at enrollment were found to be independent predictors of
      smoking cessation. Patients aged 50 years or older (odds ratio=5.05, 95%
      confidence interval 1.89-13.54), and participants with an intention to quit (odds
      ratio=6.78, 95% confidence interval 2.66-17.30) were more likely to be successful
      in quitting. In phase II, another 212 smokers of one hospital were interviewed by
      doctors in charge and provided with an additional pamphlet describing how to
      practice to dislike smoking. No significant difference in the cessation rate was
      observed between phase I and phase II (5.8% vs. 8.0%). In conclusion, there were
      no differences among the three modes of "5A", but 7.7% of the 571 outpatients
      visiting respiratory divisions quit smoking with this simple "5A". The findings
      may indicate that this simple practice at clinics is useful for smoking cessation
      strategy, although randomized trials are now required.

PMID- 16629532
TI  - Lack of association of VDR polymorphisms with Thai prostate cancer as compared
      with benign prostate hyperplasia and controls.
AB  - While still relatively low as compared to rates in the Western world, prostate
      cancer is on the increase in Asia, presumably due to change in dietary and other
      lifestyle factors. One risk factor is reported to be vitamin D (VD) and therefore
      the function of its receptor (VDR) could be of importance. In the present study
      polymorphims with functional significance in the Bsm, Apa 1 and Taq 1 genes were
      therefore compared in 28 prostate cancer (CaP), 44 benign prostate hyperplasia
      (BPH) and 30 control cases in Thailand. None demonstrated any significant
      variation in distribution within these three groups and therefore we conclude
      that vitamin D may not be major risk factor for prostate cancer in this
      population. However, there is considerable variation in the distribution
      frequencies from country to country and this, combined with differences in sun
      exposure, means that the results may not be extrapolated to the general case.

PMID- 16629533
TI  - Chemoprevention by Butea monosperma of hepatic carcinogenesis and oxidative
      damage in male wistar rats.
AB  - In this communication, we document chemopreventive effects of Butea monosperma
      extract on hepatic carcinogenesis and on tumor promoter induced markers and
      oxidative stress in male Wistar rats. Treatment of male Wistar rats for five
      consecutive days with 2-AAF i.p. induced significant hepatic toxicity, oxidative
      stress and hyperproliferation. Pretreatment of B.monosperma extract (100 and 200
      mg/kg body weight) prevented oxidative stress by restoring the levels of
      antioxidant enzymes and also prevented toxicity at both doses. The promotion
      parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF
      administration in diet with partial hepatectomy (PH) were also significantly
      suppressed dose dependently by B. monosperma. Thereafter, we proceeded with
      studies on rat liver carcinogenesis. After fourteen days of DEN treatment,
      dietary administration of 2-AAF with PH resulted in a 100% incidence of tumors in
      the animals. However, B.monosperma caused reduction in the number of tumors/ rat
      and percentage of tumor bearing rats at the end of the study, as confirmed
      histologically. Thus, our data suggest that B.monosperma extract is a potent
      chemopreventive agent which suppresses 2-AAF-induced hepatic carcinogenesis and
      oxidative damage in Wistar rats. The protective activity of the plant might be
      due to the two major constituents (butrin and isobutrin).

PMID- 16629534
TI  - Classification of risk occupation for benzene exposure by urine trans, trans
      munconic acid level.
AB  - Leukemogenesis due to benzene exposure is of particular concern because of
      ongoing exposure to thousands of workers in industrial plants. Monitoring of at
      risk workers is recommended and of several biomarkers, urine trans,trans-muconic
      acid (ttMA) determination is a helpful test. The aim of this work was to classify
      risk occupation for benzene exposure by urine ttMA level. Here, the author
      compared exposure risk ratios from 6 previous reports concerning urine ttMA
      determination. Of interest, the high risk occupations were found to be those
      which have direct contact with benzene in environmental ambient air, with
      petroleum fuel as the common source.

PMID- 16629535
TI  - Early experience of sexual intercourse--a risk factor for cervical cancer
      requiring specific intervention for teenagers.
AB  - There is consensus that the main risk factor for cervical cancer development is
      persistent infection with high-risk group human papilloma viruses (HPVs),
      together with smoking, and reproductive history. Since sexual behaviour
      determines exposure to HPVs and the adolescent period may be particularly
      important in this regard it is of interest to consider behavioural determinants
      of teenagers. In one survey conducted in Khon Kaen, Thailand, some 62% percent of
      male and 19.3 % of female respondents aged 13-15 years reported having
      experienced sexual desire, and 19.1% of male and 4.7 % of female respondents
      admitted to sexual intercourse. The possibility that this might impact on HPV
      infection rates, with added risk due to the physical trauma associated with
      pregnancy and illegal abortions, indicates that more attention needs to education
      of early teens, not only for avoidance of HIV and AIDS, but also for prevention
      of cervical cancer.

PMID- 16629536
TI  - Evaluation of efficacy of self breast examination for breast cancer prevention: a
      cost effective screening tool.
AB  - Breast cancer is the most prevalent neoplasm among females and every year the
      number of associated deaths increases so that there is a dire need for
      implementation of cancer screening and early detection. A survey conducted by
      various locally organised cancer registries indicated breast cancer to be the
      most prevalent cancer among females and the second most common cause of cancer
      deaths among Pakistani women. Since Pakistani females do not generally engage in
      screening practices we argue that nurses and lady health workers should team up
      to educate women for the possible early detection of cancer using Self Breast
      Examination as a screening tool. In this paper, we attempt to evaluate the
      primary efficacy of self breast examination as an early and cost effective cancer
      screening measure, and to discuss the relation of community health nurses as well
      as the lady health workers to education of females of low income countries such
      as Pakistan to possibly lower the cancer burden.

PMID- 16629537
TI  - Overview of existing networks--is there a rationale for an Asian Cancer Registry
      Network?
AB  - Cancer registration is the base for our understanding of the burden of neoplastic
      disease in our populations at the local level. Comparability of data is essential
      for interpretation and this in turn depends on standardization of methodology and
      diagnostic and other criteria applied. If this is to be achieved across Asia,
      some form of international organization is clearly necessary. The question
      therefore should be whether the existing arrangement is adequate, and if this is
      not the case how a network in Asia might be established with due consideration of
      aims and attainable objectives. The present commentary focuses on the
      contributions made by the International Agency for Research on Cancer (IARC), the
      International Association of Cancer Registries (IACR), the European Network of
      Cancer Registries (ENCR), the North American Association of Central Cancer
      Registries (NAACCR) and individual country-based or region-based associations
      already active in Asia. An argument is presented here that there is a rationale
      for an Asian Network of Cancer Registries, working alongside and learning from
      the existing international organizations to promote effective cancer registration
      and disease prevention in Asia.

PMID- 16629538
TI  - Levels of myosin heavy chain mRNA transcripts and content of protein isoforms in
      the slow soleus muscle of 7 month-old rats with altered thyroid status.
AB  - Skeletal muscles of small rodents contain four main fiber types, namely type 1,
      2A, 2X/D and 2B fibers containing myosin heavy chain (MyHC) 1, 2a, 2x/d and 2b
      isoforms. Each of these MyHC isoforms is the product of a distinct gene and their
      expression is believed to be primarily transcriptionally controlled. In most rat
      muscles, messenger RNA (mRNA) transcripts for MyHC1, 2a, 2x/d and 2b and their
      corresponding protein products were found with the exception of the soleus
      muscle, where typically only MyHC1 and 2a transcripts and protein isoforms were
      demonstrated under normal conditions. Here we show the expression of all four
      MyHC1, 2a, 2x/d and 2b mRNA transcripts in the soleus muscle under normal
      conditions in euthyroid, as well as in experimental hypothyroid and hyperthyroid
      (with the exception of 2b MyHC transcript) 7-month-old female inbred Lewis rats.
      This is not matched, however, by the appearance of corresponding four isoforms,
      as we have found that 2x/d and 2b protein isoforms are not present at levels
      detectable by SDS-PAGE. We also show that the chronic hypothyroid and
      hyperthyroid status affects the expression of MyHC isoforms both at the mRNA and
      protein levels.

PMID- 16629542
TI  - Fellowship training in palliative medicine.

PMID- 16629543
TI  - Hospice and palliative medicine: ten years has made a difference.

PMID- 16629544
TI  - Antiemetic properties of megestrol acetate.

PMID- 16629545
TI  - Radiotherapy for palliation of lung cancer in patients with compromised hearts.

PMID- 16629546
TI  - Communicating bad news to patients in circumstances in which there is no
      protocol.

PMID- 16629547
TI  - Poetry in palliative care.

PMID- 16629548
TI  - What's in a Name?

PMID- 16629549
TI  - Palliative sedation and the fear of legal ramifications.

PMID- 16629551
TI  - Billing for palliative care: an essential cost of doing business.

PMID- 16629552
TI  - Mirtazapine-induced hyponatremia in an elderly hospice patient.
AB  - BACKGROUND: Mirtazapine, which enhances central noradrenergic and serotonergic
      activity, is a commonly prescribed drug for mood disorders in elderly patients
      due to the low incidence of adverse effects. A heterocyclic antidepressant,
      mirtazapine has pharmacodynamics similar to selective serotonin reuptake
      inhibitors (SSRIs) and tricyclic antidepressants. Nevertheless, geriatric
      patients in general are more prone to experience adverse drug effects. OBJECTIVE:
      To report a case of hyponatremia in an elderly hospice patient associated with
      mirtazapine use. CASE SUMMARY: A 72-year-old Latino male with stage IV colon
      cancer entered into hospice care and was treated for major depressive disorder
      with mirtazapine. On day 6 of treatment, he was somnolent and confused. He was
      found to have severe hyponatremia (serum sodium of 116 mmol/L) without any
      immediately identifiable physiologic cause. His previous sodium levels were
      within normal limits over a 6-month period including when mirtazapine was
      started. Upon discontinuation of mirtazapine, the patient's mental status
      improved, and his sodium level returned to normal. DISCUSSION: Hyponatremia
      resulting from antidepressant use, particularly SSRIs, is rare in the general
      population, but in the elderly population the incidence increases because of
      multiple factors. There are few reports in the literature regarding hyponatremia
      induced by mirtazapine. CONCLUSIONS: The benefit of treating mood disorders at
      the end of life outweighs the risks of untreated depression. Hyponatremia,
      although an uncommon adverse effect of mirtazapine therapy, should be considered
      in the elderly patient with altered mental status or delirium who has recently
      initiated mirtazapine therapy.

PMID- 16629553
TI  - Acute retrograde amnesia as first presentation in terminal metastatic cancer.
AB  - A case is presented of a 2-week onset of acute retrograde amnesia as initial
      presentation, caused by presumed cancer. While acute retrograde amnesia has been
      reported in the literature, a report linked to cancer has not previously been
      published. An 82-year-old Caucasian woman presented to the emergency department,
      with 3-day history of increasing confusion and mild frontal headaches. Until 2
      weeks previously she had been living on her own and coping with her activities of
      daily life. She believed very firmly that she was living with her husband in the
      house in which they lived in over 30 years ago. A magnetic resonance imaging scan
      demonstrated a lesion extending from cortex anteriorly to the right basal ganglia
      posteriorly. Postgadolinium enhancement was consistent with a diagnosis of a
      primary or secondary neoplasm. In some patients, cognitive behaviour changes or
      amnesia is the sole presenting feature of a serious underlying pathology. A
      lesion in either the temporal or frontal lobe can lead to this presentation. A
      family conference was convened and there was decision to take a conservative
      approach and not to investigate further. She was discharged to the care of her
      daughter and died 3 months later without return of her memory.

PMID- 16629554
TI  - Telehospice support for elder caregivers of hospice patients: two case studies.
AB  - This project reports on the experience of two hospice caregivers using videophone
      technology to enhance communication with their care providers. The data show the
      overall satisfaction and technical feasibility with videophone technology in home
      hospice. The case studies have great implication for future research because they
      reveal many unexpected issues relevant for future large-scale interventions.

PMID- 16629555
TI  - Access to hospice for African Americans: are they informed about the option of
      hospice?
AB  - OBJECTIVE: To examine whether African Americans are informed about hospice
      services, and to examine demographic or disease factors that may influence
      receipt of information about hospice. DESIGN: Retrospective cohort study.
      SETTING: Twenty-two states that accounted for nearly 70% of deaths in the United
      States in 2000. MEASUREMENTS: A mortality follow-back survey was conducted. Based
      on sampled death certificates from 22 states, informants listed on the death
      certificates were contacted by telephone regarding the decedent's dying
      experience. Among those persons not receiving hospice services, the respondents
      were asked if hospice was presented as an option for care at the end of life.
      RESULTS: Of 1578 interviews, 111 decedents were non-Hispanic, African Americans
      (average age, 71.5 years; 56% female). Of those, 32 (30.3%) of the decedents
      received hospice services, while 77 (68.5%) did not. Slightly more than half of
      African Americans (60; 53.8%) were not informed about hospice services and 12
      (8.9%) were informed but did not enroll. Cancer sufferers were more likely to be
      counseled about hospice (p = 0.001). CONCLUSION: Slightly more than half of
      African Americans were not informed about hospice services, and of those who were
      informed, cancer was the leading cause of death. Information about hospice should
      be provided to patients regardless of diagnosis, and dissemination of information
      should be done aggressively in the African American community in an effort to
      make hospice a viable option for end-of-life care.

PMID- 16629556
TI  - A needs assessment: Fellowship Directors Forum of the American Academy of Hospice
      and Palliative Medicine.
AB  - The Fellowship Directors Forum, a special interest group of the American Academy
      of Hospice and Palliative Medicine (AAHPM) initiated an assessment of the needs
      of directors of fellowship programs in the emerging specialty of hospice and
      palliative care. One major finding, which may contribute to understanding the
      needs of other new disciplines, is that directors come into this role with
      clinical and teaching experience, but lacking administrative, educational, and
      management skills perceived as necessary to success. A study team collected data
      from current and former fellowship directors across the United States using an
      online survey and telephone interviews. The survey was sent to 60 current and
      former directors, with a 60% response rate, and 16 randomly selected directors
      were interviewed. Results showed that directors believe development of an outcome
      based standardized curriculum is vitally important to advancement of the field,
      and that this should be developed collaboratively through the Forum. Although
      directors were confident of their own clinical and teaching skills, directors
      identified a lack of adequate training and experience in several management and
      educational skill areas critical to running a successful fellowship program. The
      study team made several recommendations: develop models from parts of existing
      programs that can be incorporated into a standardized curriculum to meet
      Accreditation Council of Graduate Medical Education (ACGME) requirements; provide
      workshops and toolkits for new directors to address the lack of management and
      educational skills; and establish new communication methods through more or
      longer forum meetings, a dedicated website, and an online discussion group.

PMID- 16629557
TI  - Respiratory tract secretions in the dying patient: a comparison between
      glycopyrronium and hyoscine hydrobromide.
AB  - The evidence for the management of respiratory tract secretions (RTS) in dying
      patients with antimuscarinic drugs remains inconclusive. This study investigated
      the effectiveness of glycopyrronium versus hyoscine hydrobromide in controlling
      RTS using the Liverpool Care of the Dying Pathway (LCP) in 72 patients matched
      for age, diagnosis, and gender who died on a 30-bed specialist palliative care
      unit. All patients in the glycoypyrronium group had some response to
      glycopyrronium, whereas 22% of patients in the hyoscine group had no response to
      hyoscine hydrobromide. There was a significant difference in overall response
      between the two groups (p < 0.01). Twenty-eight percent of patients in the
      glycopyrronium and 42% of patients in the hyoscine group died with RTS present.
      There was no statistically significant difference in the levels of agitation
      following administration of either drug. This study provides further evidence
      that the LCP can be a useful tool in the evaluation of new drugs for symptom
      control in dying patients and suggests that glycopyrronium may be at least as
      effective in controlling RTS in dying patients as hyoscine hydrobromide.

PMID- 16629558
TI  - Palliative management of pressure ulcers and malignant wounds in patients with
      advanced illness.
AB  - BACKGROUND: Pressure ulcers and malignant wounds are prevalent in populations
      with advanced illness. In these populations, the goals of care may shift from a
      primary focus on healing to a focus on wound management, palliation and comfort.
      Many complications associated with these wounds must be palliated. OBJECTIVE:
      This review explores the palliative approach to managing pressure ulcers and
      malignant wounds in patients with advanced illness. DESIGN: A comprehensive
      search of MEDLINE, CINAHL, and Cochrane Databases for articles addressing wound
      management and palliation was performed. We also reviewed online wound care
      resources and textbooks related to the field. CONCLUSIONS: The key to good wound
      care is prevention if possible, ongoing wound assessment, correct choice of
      dressing and use of available adjuvant therapies. The ultimate goals of
      palliative wound care are to control pain, to manage infection, odor, bleeding,
      and exudate, and to maintain a good quality of life for the patient and
      caregiver.

PMID- 16629559
TI  - The Edmonton Symptom Assessment System as a screening tool for depression and
      anxiety.
AB  - PURPOSE: Mood disorders are among the most important psychiatric problems in
      patients with cancer. However, they are frequently underdiagnosed and therefore
      undertreated. This may lead to difficulties with symptom control, social
      withdrawal, and poor quality of life. This study was conducted to evaluate the
      screening performance of the Edmonton Symptom Assessment System (ESAS) for
      depression and anxiety, compared to Hospital Anxiety and Depression Scale (HADS).
      METHODS: We retrospectively reviewed and analyzed ESAS and HADS data collected
      from three previous clinical trials conducted by our group. The diagnosis of
      depression and/or anxiety, and moderate/severe depression and/or anxiety made
      when patients scored 8 or more, and 11 or more in HADS questionnaire,
      respectively. The sensitivity, specificity, positive, and negative predictive
      values for ESAS were calculated. RESULTS: Of 216 patients analyzed, the median
      (range) score for depression was 2 (0-10) and anxiety 3 (0-10) using ESAS, and 6
      (0-16) and 7 (0-19) using HADS, respectively. A cut off of 2 out of 10 or more in
      the ESAS gave a sensitivity of 77% and 83% with a specificity of 55% and 47% for
      depression and moderate/severe depression, respectively. A cutoff of 2 out of 10
      or more in the ESAS gave a sensitivity of 86% and 97%, and a specificity of 56%
      and 43% for anxiety and moderate/severe anxiety, respectively. CONCLUSION: Our
      data suggest that the ideal cutoff point of ESAS for the screening of depression
      and anxiety in palliative care is 2 out of 10 or more. More research is needed to
      define the ideal cutoff point for screening of severe depression and anxiety.

PMID- 16629560
TI  - Self-reported quality of life in amyotrophic lateral sclerosis.
AB  - OBJECTIVES: To continuously assess overall quality of life (QOL) and disease
      progression in patients with amyotrophic lateral sclerosis (ALS) at different
      stages of the disease and compare the results between these two variables.
      DESIGN/SUBJECTS: Twenty-six patients with ALS were interviewed with a
      questionnaire to assess their QOL from 0 to 10, where 10 is the highest QOL and
      questions concerning physical function, psychological status, and civil status.
      Their disease progression was estimated by ALS Functioning Rating Scale (ALS
      FRS). Nine patients were interviewed only once and 17 patients were interviewed 2
      7 times. The interviews were repeated every second visit (range, 4-7 months). All
      values were ranked and linear regression was used to calculate the slope of QOL
      and ALS FRS. RESULTS: The mean QOL value for all 26 patients was 5.8 (0-10-point
      scale). For the 17 patients interviewed 2-7 times, which correspond to a follow
      up period of 5-28 months, there was no significant change in QOL-value (p =
      0.247) among the interviews despite a significant disease progression (p =
      0.0001). CONCLUSION: It can be concluded that ALS does not necessarily result in
      a low overall QOL and that despite disease progression overall QOL changes only
      slightly over time.

PMID- 16629561
TI  - Objective evaluation of physical function in patients with advanced lung cancer:
      a preliminary report.
AB  - PURPOSE: This prospective study was designed in order to compare the most common
      subjective measurements of physical function in patients with advanced lung
      cancer with an objective physical functional test (Simmonds Functional Assessment
      Tool [SFA]). PATIENTS AND METHODS: One hundred patients agreed to participate and
      complete the study before or after their outpatient medical oncology appointment.
      Patients underwent assessment using the Karnofsky, the Brief fatigue Inventory,
      The Functional Assessment of Cancer Therapy-Lung patients (FACT-L) and the
      Edmonton Symptom Assessment Scale (ESAS). These results were compared to the SFA
      tool. The SFA consists of six tasks: tying a belt, putting coins in a cup,
      reaching above head, standing up/sitting down, reaching forward and walking 50
      feet. RESULTS: Ninety-nine patients completed the study over 8 months: median
      Karnofsky performance status was 85 (70 to 100), Edmonton Symptom Assessment
      Scale (ESAS) score (0 to 10) was generally low (0.5 to 2.8). SFA scores were
      significantly different in patients compared to a control group. The correlation
      between the subscales of the SFA and the Karnofsky, the Brief Fatigue Inventory,
      The FACT-L and the ESAS was generally low to moderate (r values: 0.22 to 0.38).
      There was generally a moderate correlation between the different subjective
      scales (r values: 0.3 to 0.62). CONCLUSION: Adherence to the SFA tool was
      excellent. The low to moderate correlation between the abnormalities found in the
      objective SFA and the subjective fatigue tests suggest that objective evaluation
      of the functional capacity provides a potentially useful and independent end
      point for clinical trials and therapeutic interventions. These assessment tools
      should be used complementary to each other to better assess the functional status
      of patients with advanced lung cancer. Large trials of objective functional
      assessment are justified.

PMID- 16629562
TI  - Perceptions of inadequate health care and feelings of guilt in parents after the
      death of a child to a malignancy: a population-based long-term follow-up.
AB  - BACKGROUND: Parental feelings of guilt can be a serious problem after the death
      of a child to a malignancy. This study identified predictors of feelings of guilt
      in parents during the year after a child's death. METHODS: The Swedish Cause of
      Death Register and Swedish Cancer Register were used to identify all parents in
      Sweden who had a child who died of a malignancy between 1992-1997. RESULTS: Among
      parents not reporting recent depression, those who were not confident that their
      child would immediately receive help from the staff in the hospital while he or
      she was sick with a malignancy (compared to those who felt partly or entirely
      sure, relative risk [RR] 4.0; 95% confidence interval [CI] 2.1-7.6), were at
      increased risk for reporting daily or weekly feelings of guilt in the year after
      the child's death. Parents who perceived that the staff in the pediatric cancer
      ward were incompetent were at increased risk (compared to parents reporting
      partial or total competence, RR 3.7; 95% CI 1.6-8.6). Compared to parents
      reporting that their children had moderate or much access, those who felt their
      children had little or no access to pain relief, dietary advice, anxiety relief,
      and relief of other psychological symptoms beside anxiety were at more than two
      times greater risk for reporting feelings of guilt. CONCLUSIONS: Bereaved
      parents' perceptions of inadequate health care were associated with subsequent
      feelings of guilt during the year following their child's death due to a
      malignancy.

PMID- 16629563
TI  - End-of-life decisions and palliative care in a children's hospital.
AB  - OBJECTIVE: To investigate clinical and demographic factors affecting the nature
      of end-of-life decisions and pediatric palliative care. DESIGN: Charts of 236
      expired children were retrospectively reviewed for presence of endof- life care
      (EOLC) discussions and spiritual support, the nature of EOLC decisions, and the
      degree of opioid analgesics (OA) and sedatives (SDT) administration. RESULTS:
      Approximately 60% of patients had EOLC discussion, of whom 87.4% obtained an EOLC
      decision, mostly opting for withholding therapy (68.8%). Presence of EOLC
      discussion was associated with a longer hospital stay (univariate analyses: odds
      ratio [OR] = 1.9; p < 0.029), higher number of failed organs (OR = 2.5; p <
      0.003), chronic illnesses (OR = 2.4; p < 0.002), spiritual support (OR = 1.8; p <
      0.028) and respiratory diseases (OR = 3.1; p < 0.0006). Younger patients and
      those with higher number of failed organs were more likely to have withdrawal of
      therapy (OR = 10.9 and 6.0; p < 0.0001 and <0.002, respectively), whereas
      patients with chronic illness opted for withholding of therapy (OR = 3.1; p <
      0.006). Spiritual support was associated with higher use of both OA and SDT (OR =
      1.9 and 2.3; p < 0.014 and p < 0.005, respectively). Younger patients received
      less OA and SDT (OR = 0.2 and 0.4, respectively; p < 0.0001). Multivariate
      analyses showed that EOLC discussion is associated with higher use of OA and SDT
      (OR = 4.4 and 4.2; p < 0.00001 and p < 0.0001, respectively), whereas younger age
      is associated with withdrawal of therapy (OR = 8.3; p < 0.0005) and lower use of
      SDT (OR = 0.23; p < 0.0001). CONCLUSIONS: Patterns of care at the end of life
      vary in children with differing clinical and demographic characteristics. Because
      EOLC discussions are associated with greater focus on palliative care, strategies
      to enhance EOLC communications for pediatric patients should be further
      evaluated.

PMID- 16629564
TI  - The impact of gender and marital status on end-of-life care: evidence from the
      National Mortality Follow-Back Survey.
AB  - BACKGROUND: End-of-life care poses a growing clinical and policy concern. Gender
      and marital status may play important roles in shaping end-of-life care.
      OBJECTIVE: To examine gender and marital status differences across multiple end
      of-life care outcomes: primary residence in the last year of life (LYL), place of
      death, hospice use, type of formal and informal caregivers, and primary payment
      source for end-of-life care. DESIGN: Retrospective cohort study using bivariate
      analyses and multivariate logistic regression. PARTICIPANTS: A nationally
      representative sample of 12,771 individuals who died of natural causes, from the
      1993 National Mortality Followback Survey. RESULTS: After multivariate
      adjustment, the only gender differences in end-of-life care were that women were
      more likely to receive formal or informal care in the LYL and more likely to be
      on Medicaid. After adjustment, unmarried individuals (widowed,
      divorced/separated, and single) were more likely than married people to live
      their LYL and die in nursing homes, less likely to receive formal or informal
      care in the LYL, and more likely to be on Medicaid. Hospice use was low, with
      minimal gender and marital status differences. CONCLUSIONS: Marital status is a
      key variable mediating gender differences in end-of-life care. Unmarried
      individuals are less likely to receive help from informal caregivers-most notably
      because of the lack of spousal care-which may explain why they are more likely to
      end up in nursing homes. Clinicians need to be aware of the impact of marital
      status on endof- life care. Policymakers should consider that women will be
      disproportionately affected by policy changes in public financing for end-of-life
      care.

PMID- 16629565
TI  - Appraisal of the Graduate End-of-Life Nursing Education Consortium Training
      Program.
AB  - BACKGROUND: Advanced practice nurses (APNs) are crucial in the provision of
      quality end-oflife care. However, little attention is devoted to palliative care
      in most graduate nursing curricula, leaving advanced practice nurses poorly
      prepared to meet the needs of those approaching the end of their lives.
      OBJECTIVE: The purpose of the graduate version of the End-of-Life Nursing
      Education Consortium (ELNEC-Graduate) Training Program is to provide nursing
      faculty with the knowledge and materials necessary to include palliative care
      throughout the graduate nursing curriculum. DESIGN AND SETTINGS: Sixty graduate
      nursing faculty members attended the first ELNECGraduate training course. Prior
      to attending the course, each participant completed surveys regarding the
      adequacy of end-of-life (EOL) content within their curriculum, as well as overall
      perceptions of EOL education in their university. Participants were asked to
      respond to these same questions immediately and at 12 months after completion of
      the course. RESULTS: Respondents reported significant improvements in the
      adequacy of eight areas of EOL content taught within their settings. Participants
      noted improved effectiveness in their ability to teach EOL care, of their
      curriculum in including EOL care, and of their graduate nursing students in
      providing care to the dying. The total hours of EOL content added to graduate
      nursing curricula as a result of attending ELNEC-Graduate was 18.4 +/- 17.4
      standard deviation (SD) hours. Additional unintended consequences were noted.
      CONCLUSION: The ELNEC-Graduate Program is a national initiative that effectively
      improves faculty expertise in EOL care and expands palliative care content within
      graduate nursing curricula.

PMID- 16629566
TI  - The validity and reliability of the affective competency score to evaluate death
      disclosure using standardized patients.
AB  - OBJECTIVE: To explore the validity and reliability of the affective competency
      score (ACS), compared to a global rating measure to predict overall competency to
      perform a death disclosure in a standardized patient exercise and to investigate
      useful thresholds of the ACS. METHODS: Thirty-seven fourth-year students
      underwent standardized patient training in death disclosure during a fourth-year
      emergency medicine clerkship. Students were evaluated using a checklist, an ACS,
      and a global rating assessment. ACS interrater reliability, interitem
      reliability, item-total reliability, and split-half reliability were calculated.
      Area under the curve (AUC) measurements were used to establish criterion
      validity. RESULTS: For the ACS, item-total correlations ranged from 0.76 to 0.85,
      0.76 to 0.93, and 0.42 to 0.87; the split-half reliability was 0.82 (p = 0.0001),
      0.86 (p = 0.0001) and 0.55 (p = 0.0007) for the standardized patient (SP), the
      faculty and the medical students, respectively. Interitem correlations were
      adequate. A moderate interrater correlation of the ACS was observed between the
      faculty observer and the SP (r = 0.47; p = 0.04); however, the medical students'
      self evaluation did not correlate significantly with either the SP (r = -0.04; p
      = 0.79), or the faculty observer (r = 0.00; p = 0.99). The AUC for was 0.98 (95%
      confidence interval [CI] 0.94 to 1.00), 0.87 (95% CI 0.73 to 0.99), and 0.74 (95%
      CI 0.53 to 0.95) for the faculty, SP, and medical student, respectively.
      CONCLUSIONS: The ACS may be a valid, reliable, and useful measure to assess
      communication skills by faculty or SPs in this setting. At an ACS score of 16,
      19, and 21 points for faculty, SPs, and medical students, respectively, there is
      100% specificity for the detection of competency assessed on a global rating.
      However, the ACS appears to have limited reliability and validity when used by
      medical students.

PMID- 16629567
TI  - Manualized communication interventions to enhance palliative care research and
      training: rigorous, testable approaches.
AB  - Palliative care practice requires excellent communication between the patient,
      family, and clinical team. Experts in the field have proposed a variety of
      communication interventions that can be used in the palliative care setting.
      However, these interventions are at a high level of generality: the specifics of
      each intervention are not well codified; the individual steps in each
      intervention are not easily reproducible and thus not comparable between
      practitioners; the methods to measure adherence to these communication protocols
      have not been established; and there is little detail on how to adapt these
      general interventions to the individual patient and family. Therefore, we lack
      good evidence for the efficacy of these recommendations. This paper makes the
      case for development of structured, testable approaches to communication that
      will inform clinical practice and communication training. To do so, palliative
      care communication should be conceived as a formal medical and psychosocial
      intervention-a potential treatment with risks and benefits to be systematically
      researched and operationalized in the same manner as medication interventions. As
      we illustrate, psychotherapy research has faced the same challenges in the past
      and has utilized manualized treatments to meet its goals. Through such
      approaches, we can begin to address the most basic intervention questions such as
      protocol efficacy, dose-response, side effects, and the optimal process and
      content of communication with the patient and family. The advantages of
      manualized communication approaches; some concepts underlying manual
      construction; and challenges to extending manualized communication to the
      palliative care domain are discussed.

PMID- 16629568
TI  - What is most important for you to achieve?: an analysis of patient responses when
      receiving palliative care consultation.
AB  - BACKGROUND: Hospitalized patients with a wide range of serious, but not
      necessarily terminal illnesses are now receiving palliative care consultations.
      The purpose of this report is to describe what palliative care patients say is
      "most important to achieve" at the time of initial consultation. METHODS: We
      conducted a retrospective descriptive content analysis of patient responses to
      the question "What is most important for you to achieve?" recorded at the time of
      initial inpatient palliative care consultation. Two hundred fifteen patient
      records had documented first-person patient responses recorded. These responses
      were independently reviewed and categorized in a four-phase iterative process.
      RESULTS: Responses were divided into four major categories: (1) Improving quality
      and meaning ("I want to be able to sit on my front porch and watch the farm go
      by.") (52%); (2) Achieving relief or comfort ("Can you get rid of my pain?")
      (34%); (3) Altering the trajectory of illness ("If there is a treatment that can
      make me well, I want it.") (22%); and (4) Preparing for dying ("I am not afraid
      of dying. I just don't want to suffer.") (11%). Five percent of responses were
      unable to be reliably categorized ("You ask hard questions."). Some respondents
      gave more than one response, so the total is greater than 100%. CONCLUSIONS:
      Patients receiving palliative care consultation give a wide range of responses to
      the question "What is most important for you to achieve?" Such patient-centered
      inquiry about priorities deserves more systematic study in the future if patient
      specific goals are to be a marker of high-quality palliative care.

PMID- 16629569
TI  - Symptom management: the growing evidence base.

PMID- 16629570
TI  - Symptom control in palliative care--Part I: oncology as a paradigmatic example.
AB  - Achieving the best quality of life for patients and their families when a disease
      becomes progressive and no longer remains responsive to curative therapy is the
      primary goal of palliative care. A comprehensive care plan focusing on control of
      physical symptoms as well as psychological, social, and spiritual issues then
      becomes paramount in that context. Symptom assessment and treatment are a
      principle part of palliative care. This paper is the first of three in a series
      addressing non-pain symptoms, which are frequently encountered in the palliative
      care populations. The most frequent non-pain symptoms are constipation, chronic
      nausea and vomiting, anorexia, dyspnea, fatigue, and delirium. As symptoms are
      subjective, their expression varies from patient to patient, depending on the
      individual patient's perception and on other factors such as psychosocial issues.
      While symptoms are addressed individually, patients frequently have multiple
      coexisting symptoms. Generally told, once the intensity of a symptom has been
      assessed, it is necessary to assess the symptom in the context of other symptoms
      such as pain, appetite, fatigue, depression, and anxiety. Given that fact,
      adopting a multidimensional assessment allows for formulation of a more effective
      therapeutic strategy. More pertinently, this paper highlights the management of
      non-pain symptoms as an integral part of patient care and reviews the
      pathophysiologies, causes, assessment, and management of constipation, chronic
      nausea, and vomiting, each of which is common among the palliative care
      population.

PMID- 16629571
TI  - Symptom control in palliative care--Part II: cachexia/anorexia and fatigue.

PMID- 16629572
TI  - Symptom control in palliative care--Part III: dyspnea and delirium.

PMID- 16629573
TI  - Sleep disturbance in supportive care of cancer: a review.
AB  - Insomnia constitutes a significant source of suffering for patients with cancer
      as they move through the course of treatment and advanced illness. Practicing
      physicians and caregivers are challenged to address this troubling symptom
      without the benefit of an extensive literature specific to this population. There
      is evidence to suggest that the routine clinical management of patients with
      cancer with insomnia is discordant with best practices documented in the
      available literature. This paper reviews the literature to characterize the sleep
      disturbances experienced by patients with cancer. The evaluation and management
      of insomnia in patients with cancer is reviewed, and a management plan based on
      available literature is proposed.

PMID- 16629574
TI  - Avoiding iatrogenic harm to patient and family while discussing goals of care
      near the end of life.
AB  - BACKGROUND: Treatment of suffering is a core mission of medicine. Communication
      about treatment planning with the patient and family, called the goals of care
      discussion, offers the opportunity to provide effective relief. Such
      communication is particularly important near the end of life, because many
      medical decisions are determined then by emotional considerations and personal
      values. OBJECTIVE: To define common unintended clinician behaviors, which impair
      discussion about goals of care near the end of life. To discuss the relationship
      between: (1) the medical decision-making responsibilities of patient and family,
      (2) clinician communication, (3) iatrogenic suffering, (4) the impact on medical
      decision-making, and (5) patient and family outcomes. DESIGN: Thematic literature
      review. RESULTS: The authors discuss how omission of the integral emotional and
      social elements of the goals of care discussion are reflected in five unintended
      clinician behaviors, each of which may impair medical decision-making and
      unknowingly induce patient and family suffering. We posit that such impaired
      decision-making and suffering may contribute to demands for ineffective, life
      sustaining interventions made by the patient and family or, conversely, to
      requests for hastened death. CONCLUSIONS: Understanding the challenges in the
      discussion about goals of care near the end of life will facilitate the
      development of more effective approaches to communication and shared decision
      making. The authors hypothesize how decreased suffering through improved
      communication should diminish the occurrence of depression, anxiety disorders,
      and complicated grief in the patient and survivors, potentially improving medical
      outcomes. Proposed experiments to test this hypothesis will address important
      public health goals.

PMID- 16629575
TI  - A thematic review of the spirituality literature within palliative care.
AB  - Research related to spirituality and health has developed from relative obscurity
      to a thriving field of study over the last 20 years both within palliative care
      and within health care in general. This paper provides a descriptive review of
      the literature related to spirituality and health, with a special focus on
      spirituality within palliative and end-of-life care. CINAHL and MEDLINE were
      searched under the keywords "spirituality" and "palliative." The review revealed
      five overarching themes in the general spirituality and health literature: (1)
      conceptual difficulties related to the term spirituality and proposed solutions;
      (2) the relationship between spirituality and religion; (3) the effects of
      spirituality on health; (4) the subjects enrolled in spirituality-related
      research; and (5) the provision of spiritual care. While the spirituality
      literature within palliative care shared these overarching characteristics of the
      broader spirituality and health literature, six specific thematic areas
      transpired: (1) general discussions of spirituality in palliative care; (2) the
      spiritual needs of palliative care patients; (3) the nature of hope in palliative
      care; (4) tools and therapies related to spirituality; (5) effects of religion in
      palliative care; and (6) spirituality and palliative care professionals. The
      literature as it relates to these themes is summarized in this review.
      Spirituality is emerging largely as a concept void of religion, an instrument to
      be utilized in improving or maintaining health and quality of life, and focussed
      predominantly on the "self" largely in the form of the patient. While
      representing an important beginning, the authors suggest that a more integral
      approach needs to be developed that elicits the experiential nature of
      spirituality that is shared by patients, family members, and health care
      professionals alike.

PMID- 16629576
TI  - Early diagnosis of epidural metastases #62.

PMID- 16629577
TI  - Neoplastic meningitis #135.

PMID- 16629578
TI  - Thoughts on advance directives.

PMID- 16629579
TI  - The unexpected team member.

PMID- 16629580
TI  - The doctor.

PMID- 16629581
TI  - Rotating methadone to other opioids: a lesson in the mechanisms of opioid
      tolerance and opioid-induced pain.

PMID- 16629586
TI  - JPM patient information. Prescription pain medicine: "hooking" you or helping
      you?

PMID- 16629592
TI  - Essential sequence of influenza neuraminidase DNA to provide protection against
      lethal viral infection.
AB  - Neuraminidase (NA) is one of the surface glycoproteins of influenza virus. The
      immune response induced by NA DNA in the mouse model has been proved, in our
      previous study, to be able to provide an adequate protection against the
      challenge with a homologous virus and a crossprotection against the challenge
      with a heterologous virus of the same subtype. In this paper, a series of NA
      plasmid truncates, with the nucleotides at the 5'- or 3'-terminal of A/PR/8/34
      (H1N1) NA deleted serially, were constructed by PCR. BALB/c mice were immunized
      with the plasmid truncates and challenged with homologous virus at a lethal
      dosage. The essential sequence of NA DNA to provide protection against the
      influenza virus was explored by observing the survival rates, serum anti-NA
      antibody titers, and lung virus titers of the mice. The result showed that, along
      with the increasing number of nucleotides deleted serially at the 5'- or 3'
      terminal of NA DNA, the antibody titer induced by NA DNA decreased. NA DNA lost
      its protection against the influenza virus when 60 nucleotides (or 20 amino
      acids) at the 5'-terminal or 66 nucleotides (or 22 amino acids) at the 3'
      terminal were deleted. The nt58-1299 of NA DNA may play an important role in
      protection against influenza virus.

PMID- 16629593
TI  - Chromosomal localization, copy number assessment, and transcriptional status of
      BamHI repeat fractions in water buffalo Bubalus bubalis.
AB  - Higher eukaryotes contain a wide variety of repetitive DNA, although their
      functions often remain unknown. We describe cloning, chromosomal localization,
      copy number assessment, and transcriptional status of 1378- and 673-bp repeat
      fractions in the buffalo genome. The pDS5, representing the 1378-bp fragment,
      showed FISH signals in the centromeric region of acrocentric chromosomes only,
      whereas pDS4, corresponding to 673 bp, detected signals in the centromeric
      regions of all the chromosomes. Crosshybridization studies of pDS5 and pDS4 with
      genomic DNA from different sources showed signals only in buffalo, cattle, goat,
      and sheep. Real-time PCR analysis uncovered 1234 and 3420 copies of pDS5 and pDS4
      fragments per the haploid genome, corresponding to 30 and 68 copies per
      chromosome, respectively. Analysis of cDNA from different tissues of buffalo with
      Real-time PCR showed maximum expression of pDS5 and pDS4 in the spleen and liver,
      respectively. Phylogenetic analysis of these sequences showed a close
      relationship between buffalo and cattle. The prospect of this approach in
      comparative genomics is highlighted.

PMID- 16629594
TI  - Lactase gene promoter fragments mediate differential spatial and temporal
      expression patterns in transgenic mice.
AB  - Lactase gene expression is spatiotemporally regulated during mammalian gut
      development. We hypothesize that distinct DNA control regions specify appropriate
      spatial and temporal patterning of lactase gene expression. In order to define
      regions of the lactase promoter involved in mediating intestine-specific and
      spatiotemporal restricted expression, transgenic mice harboring 100 bp, 1.3- and
      2.0- kb fragments of the 5' flanking region of the rat lactase gene cloned
      upstream of a luciferase reporter were characterized. The 100-bp lactase promoter
      reporter transgenic mouse line expressed maximal luciferase activity in the
      intestine with a posterior shift in spatial restriction and ectopic expression in
      the stomach and lung. The temporal pattern of expression mediated by the 1.3-kb
      promoter?reporter transgene increases with postnatal maturation in contrast with
      the postnatal decline mediated by the 2.0-kb promoter-reporter transgene and the
      endogenous lactase gene. The differential transgene expression patterns mediated
      by the lactase promoter fragments suggests that intestine-specific spatial and
      temporal control elements reside in distinct regions of the DNA sequences
      upstream of the lactase gene transcription start-site.

PMID- 16629595
TI  - Are viral-encoded microRNAs mediating latent HIV-1 infection?
AB  - The Human Immunodeficiency Virus type 1 (HIV-1), a member of the lentivirus
      subfamily, infects both dividing and nondividing cells and, following reverse
      transcription of the viral RNA genome, integrates into the host chromatin where
      it enters into a latent state. Many of the factors governing viral latency remain
      unresolved and current antiviral treatment regimens are largely ineffective at
      eliminating cellular reservoirs of latent virus. The recent identification of
      microRNA (miRNA) encoding sequences embedded in the HIV-1 genome, and the
      discovery of functional virus-derived miRNAs, suggests a role for RNA
      Interference (RNAi) in the regulation of HIV-1 gene expression. Recently, the
      mammalian RNAi machinery was shown to regulate gene expression epigenetically by
      transcriptional modulation, providing a direct link between RNAi and a mechanism
      for inducing latency. Interestingly, both HIV-1 Tat, and the host TAR RNA-binding
      protein (TRBP), bind to the transactivating response (TAR) RNA of HIV-1 and
      affect the function of RNAi in human cells. Specifically, TRBP, a cofactor in Tat
      TAR interactions, is a vital component of Dicer-mediated dsRNA processing. These
      novel observations support a central role for HIV-1 and associated host factors
      in regulating cellular RNAi and viral gene expression through RNA directed
      processes. Thus, HIV-1 may have evolved mechanisms to exploit the RNAi pathway at
      both the transcriptional and posttranscriptional level to affect and/or maintain
      a latent infection.

PMID- 16629596
TI  - Cloning of mouse Dab2ip gene, a novel member of the RasGTPase-activating protein
      family and characterization of its regulatory region in prostate.
AB  - Disabled homolog 2 (Drosophila) interacting protein (DAB2IP/Dab2IP) is a member
      of the GTPase-activating protein for downregulating the Ras-mediated signal
      pathway and TNF-mediated apoptosis. The downregulation of human DAB2IP mRNA
      levels was detected in prostate cancer cells due to the epigenetic regulation.
      Here, we isolated a mouse Dab2ip gene with a highly homologous sequence to that
      of the human and rat gene and mapped it at chromosome 2B. The mDab2ip gene
      contains 14 exons and 13 introns and spans approximately 65 kb. Exon1 contains at
      least three splicing variants (Ia, Ib, and Ic). The deduced amino acid sequence
      of mouse Dab2IP encompasses 1065 residues containing several unique protein
      interaction motifs as well as a Ras-like GAP-related domain, which shares a high
      homology with both humans and rats. Data from real-time RT-PCR analysis revealed
      a diverse expression pattern of the mDab2ip gene in various organs, implying
      differential regulation of this gene from various tissues. We have mapped a 1.3
      kb segment containing a 5'-upstream region from exon Ia as a promoter region (
      147/+545) in prostatic epithelial cell lines (TRAMP-C); this region is highly GC
      rich, and mDab2ip appears to be a TATA-less promoter. It appears that epigenetic
      regulation, particularly histone acetylation of the Dab2ip gene promoter, plays
      an important role in modulating its gene expression in the mouse prostate cancer
      cell.

PMID- 16629597
TI  - The gefitinib-sensitizing mutant epidermal growth factor receptor enables
      transformation of a mouse fibroblast cell line.
AB  - A specific inhibitor of the Epidermal Growth Factor Receptor (EGFR), Gefitinib,
      displays significant antitumor effects against non-small cell lung cancers
      (NSCLC) that express EGFR with mutations in their tyrosine kinase domain.
      Although previous reports have already demonstrated that oncogenic transformation
      can be induced by some mutant EGFR forms, the precise differences between mutant
      and wild-type EGFR in terms of mechanisms of transformation have not been fully
      elucidated. We show here that a murine fibroblast cell line, NR6 becomes
      transformed by an expression level of the mutant EGFR form lacking E746-A750 that
      is far less than that needed with transfected wild-type EGFR. However, the mutant
      EGFR was unable to transform NR6 in a ligand-independent manner, as was seen with
      the wild-type EGFR. The consequent biological features after transformation,
      including DNA synthesis or cell cycle progression and biochemical characteristics
      such as MAPK activation mediated by the mutant EGFR are comparable and equivalent
      to those mediated by wild-type EGFR. These data suggest that the mutant EGFR
      possesses greater ligand-dependent transformation when compared with wild-type
      EGFR, although the exact mechanisms to account for this characteristic remain to
      be defined.

PMID- 16629599
TI  - The intensive care unit as a research laboratory: developing strategies to
      prevent antimicrobial resistance.
AB  - OBJECTIVE: To assemble the available clinical data on the prevention of
      antimicrobial resistance in the intensive care unit (ICU) setting. DATA SOURCE: A
      MEDLINE database search and references from identified articles were employed to
      obtain the literature relating to the prevention of antimicrobial resistance in
      the ICU. CONCLUSIONS: The ICU presents a unique environment for the conduct of
      clinical research. The closed physical space with centralized patient management
      and efficient data recovery allows important clinical questions to be evaluated
      in a timely manner. Antimicrobial resistance has emerged as an important
      determinant of mortality for patients in the ICU. Additionally, there is
      currently a limited pipeline of new agents for the treatment of emerging bacteria
      with new resistance genes that pose an increasing threat to the ICU patient.
      Effective strategies for the prevention of antimicrobial resistance within ICUs
      are available and should be implemented aggressively. These strategies can be
      divided into non-pharmacologic infection- control strategies (e.g., routine hand
      hygiene, infection-specific prevention protocols) and antibiotic management
      strategies (e.g., shorter courses of appropriate antibiotics, narrowing of the
      antimicrobial spectrum on the basis of culture results). Additional studies
      conducted in ICUs are needed urgently to identify the optimal approaches for the
      management of antibiotics in order to balance the need for efficacy with the
      ability to minimize resistance.

PMID- 16629600
TI  - Defining the research agenda for surgical infection: a consensus of experts using
      the Delphi approach.
AB  - BACKGROUND: A substantial proportion of operative procedures are complicated by
      infections, either remote from or related to the surgical site. These infections
      account for substantive morbidity and health care costs. With limited research
      funds available to study interventions designed to either prevent or reduce the
      morbidity associated with infections in surgical patients, we developed a
      research agenda to develop priorities to aid in study design and to focus both
      human and capital resources more effectively. METHODS: A Delphi survey approach
      was used. Consensus was developed among experts in the field of surgical
      infection and the membership of the Surgical Infection Society. RESULTS: Thirty
      six experts generated a total of 62 questions that were submitted for two rounds
      of consensus ranking. A total of 31 questions were ranked in the final round and
      are available at www.sisna.org. The most highly ranked question was "Does strict
      glycemic control compared with standard care reduce the risk of surgical site
      infection in patients undergoing abdominal surgery?" Most of the questions had
      little available data, suggesting these are both important and necessary areas
      for further research. CONCLUSIONS: This research agenda, developed by a consensus
      of experts, provides direction and focus to the development of interventional
      trials geared toward reducing the morbidity associated with infections in
      surgical patients.

PMID- 16629601
TI  - Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil
      apoptosis.
AB  - BACKGROUND: Hyperglycemia is an independent risk factor for increased mortality
      of critically ill surgical patients, but despite the recognized clinical benefits
      of early insulin treatment, there is a lack of understanding of the cellular and
      molecular mechanisms behind this phenomenon. We hypothesized that
      polymorphonuclear neutrophils, the first line of the innate immune defense
      system, suffer from altered apoptotic turnover when exposed to hyperglycemic
      conditions, ultimately decreasing the number of viable cells active at a site of
      infection. METHODS: Venous blood samples were drawn from 10 volunteers and
      incubated for 0.5 or 24 h in a 1:10 dilution with RPMI 1640 medium at various
      glucose and insulin concentrations. Mannitol was used to control for increased
      osmolarity. In addition, all samples were incubated either with low-dose
      lipopolysaccharide (LPS) (1 ng/mL) or without LPS. Neutrophils were extracted
      using Ficoll-Hypaque density centrifugation and stained with annexin V and
      propidium iodide. Fluorescence was detected by flow cytometry and analyzed using
      CellQuest software. RESULTS: The mean percentage of apoptotic neutrophils after
      24 h of incubation at physiologic glucose concentrations (100 mg/dL) was 42.2 +/-
      4.1%; exposure to low-dose LPS decreased this number to 18.4 +/- 2.5% (p < 0.01).
      Neither the exposure to low (10 mg/dL) nor increasingly high (200 or 400 mg/dL)
      glucose concentrations altered these percentages significantly. Exposing whole
      blood to increasing osmolarity (addition of 5.5 mM and 16.5 mM mannitol to
      simulate 200 and 400 mg/dL glucose) led to a mean absolute reduction of the
      percentage of apoptotic neutrophils to 34.6 +/- 3.6% (+5.5 mOsm; p < 0.05) and
      32.3 +/- 4.5% (16.5 mOsm; p < 0.01), respectively. CONCLUSIONS: The ability of
      neutrophils to enter their apoptotic program in cultured whole blood withstands
      short-term changes in glucose and insulin concentrations. Neither hyperglycemia
      nor hypoglycemia led to a significant alteration of the apoptotic turnover of
      these cells, suggesting that the increased rate of infectious complications in
      short-term hyperglycemic critically ill patients may not be traced to increased
      apoptosis of neutrophils. However, isolated hyperosmolarity reduces neutrophil
      apoptosis, an observation that may warrant future investigation.

PMID- 16629602
TI  - Effect of aspiration pneumonia-induced sepsis on post-burn cardiac inflammation
      and function in mice.
AB  - INTRODUCTION: Numerous studies have found that burn injury alters immune
      function, predisposing the subject to infectious complications. We developed a
      mouse model of burn injury complicated by either gram-positive or gram-negative
      infection and hypothesized that post-burn infection would exacerbate the
      myocardial cytokine responses and contractile dysfunction characteristic of
      either sepsis alone or burn alone. METHODS: Adult C57 BL6 mice were given burn
      injury over 40% of the total body surface area and conventional fluid
      resuscitation (lactated Ringer's solution, 4 mL/kg/% burn) followed on day 7 by
      intratracheal administration of 1 x 10(5) cfu of either Streptococcus pneumoniae
      or Klebsiella pneumoniae or saline. Mice received fluid resuscitation (2 mL of
      lactated Ringer's intraperitoneally) again after bacterial challenge.
      Cardiomyocyte cytokine secretion and the contractile function of isolated hearts
      (Langendorff perfusion) were examined in vitro 24 h after bacterial challenge.
      RESULTS: Infectious challenge seven days after burn injury exaggerated the
      inflammatory cytokine responses over those observed with either burn alone or
      gram-positive or gram-negative infection alone (tumor necrosis factor-alpha:
      sham, 72 +/- 9 pg/mL; burn alone, 176 +/- 6 pg/mL, Klebsiella pneumoniae alone,
      337 +/- 8 pg/mL; Streptococcus pneumoniae alone, 184 +/- 2 pg/mL; burn +
      Klebsiella, 476 +/- 14 pg/mL; burn + Streptococcus, 351 +/- 6 pg/mL). Myocardial
      contractile depression was evident in the burn alone, infection alone, and burn
      plus infection groups, regardless of the organism selected to produce pneumonia
      related sepsis. CONCLUSIONS: Gram-negative or gram-positive infection exacerbated
      the myocardial inflammation seen with burn alone or infection alone. The
      availability of a mouse model of burn injury complicated by pneumonia-related
      sepsis will allow use of genetically engineered mice to examine further the
      mechanisms by which burn injury increases susceptibility to infection.

PMID- 16629603
TI  - Factors associated with mortality in critically injured trauma patients who
      require simultaneous cultures.
AB  - BACKGROUND: In trauma patients surviving their initial injuries, infectious
      complications and multiple organ failure represent the major causes of death
      after the first 72 hours. Critically injured trauma patients frequently have
      bacteria recoverable simultaneously from multiple culture sites; the clinical
      significance of this event is unknown. The objective of this study was to
      identify the association between growth patterns of multiple site cultures and
      mortality among critically injured trauma patients. METHODS: We performed a
      retrospective chart review collecting demographic and medical data on admissions
      to a state-designated Level I trauma center from April 2000 to December 2002. The
      inclusion criteria were age >17 years, admission to the trauma intensive care
      unit (TICU), and simultaneous sampling of blood, sputum, and urine in the setting
      of fever of undetermined origin or alteration in the white blood cell count. Four
      mutually exclusive groups were developed according to the number of positive
      culture sites. We used standard statistical analysis and multivariate logistic
      regression. RESULTS: During the study period, 3,402 patients were admitted to the
      trauma service of whom 124 met the inclusion criteria. Eighty percent of these
      (99) were male, and the average age was 41 years. The median TICU stay was 17
      days. The mortality rate was 24.2% (30 nonsurvivors). The survivors and non
      survivors were comparable in injury severity score (ISS), initial base deficit,
      initial hematocrit, initial blood pressure, and hospital length of stay (p >
      0.05), whereas age (p = 0.03), female sex (p = 0.04), and TICU stay (p < 0.01)
      were higher among non-survivors. More non-survivors showed growth of
      microorganisms in simultaneous blood, sputum, and urine cultures (p = 0.02). By
      multivariate analysis, adjusting for age, sex, and TICU length of stay, patients
      with growth of microorganisms in simultaneous cultures (blood, sputum, and urine)
      had a 3-fold greater mortality rate (OR, 3.20; 95% CI 1.05, 9.73). CONCLUSIONS:
      In this group of patients, growth of bacteria in simultaneous cultures was
      associated with higher mortality-a factor that may be considered a poor
      prognostic indicator. This factor requires further studies to explore the
      relation with survival in critically injured patients.

PMID- 16629604
TI  - The other fungi: it's not just Candida albicans anymore.
AB  - BACKGROUND: Candida albicans continues to be the fungus most often causing
      disease in surgical patients, but with the treatment of an increasing number of
      critically ill and immunosuppressed patients, other candidal and non-candidal
      fungal pathogens are becoming more common. METHODS: Review of current practice
      and guidelines. RESULTS: The presentation and management of non-C. albicans
      fungal infections differs depending on the genus and species. The availability of
      newer anti-fungal agents has in many cases improved outcomes or decreased
      toxicities associated with these diseases. CONCLUSIONS: Although such infections
      are still relatively uncommon, a working knowledge of infections with non-C.
      albicans fungi may be beneficial for surgeons, who are likely to encounter such
      patients both primarily and in consultation. Prompt recognition and treatment of
      these diseases should improve outcomes.

PMID- 16629615
TI  - Degenerative and spontaneous regenerative processes after spinal cord injury.
AB  - Spinal cord injury results in acute as well as progressive secondary destruction
      of local and distant nervous tissue through a number of degenerative mechanisms.
      Spinal cord injury also initiates a number of endogenous neuroprotective and
      regenerative responses. Understanding of these mechanisms might identify
      potential targets for treatments after spinal cord injury in humans. Here, we
      first discuss recent developments in our understanding of the immediate traumatic
      and subsequent secondary degeneration of local tissue and long projecting
      pathways in animal models. These include the inflammatory and vascular responses
      during the acute phase, as well as cell death, demyelination and scar formation
      in the subacute and chronic phases. Secondly, we discuss the spontaneous axonal
      regeneration of injured and plasticity of uninjured systems, and other repair
      related responses in animals, including the upregulation of regeneration
      associated genes in some neurons, increases in neurotrophic factors in the spinal
      cord and remyelination by oligodendrocyte precursors and invading Schwann cells.
      Lastly, we comment on the still limited understanding of the neuropathology in
      humans, which is largely similar to that in rodents. However, there also are
      potentially important differences, including the reduced glial scarring,
      inflammation and demyelination, the increased Schwannosis and the protracted
      Wallerian degeneration in humans. The validity of current rodent models for human
      spinal cord injury is also discussed. The emphasis of this review is on the
      literature from 2002 to early 2005.

PMID- 16629616
TI  - Collateral sprouting as a target for improved function after spinal cord injury.
AB  - Functional recovery after spinal cord injury might be improved by enhancing the
      extent of innervation through stimulation of collateral sprouting, which is the
      growth of a new axon along the shaft of a non-injured axon. This review discusses
      (1) the spontaneous collateral sprouting of uninjured motor and sensory systems
      that has been shown after spinal cord injury in animal models, (2) experimental
      treatment strategies that are being developed to enhance collateral sprouting in
      motor systems and to reduce sensory sprouting which is associated with autonomic
      dysreflexia and pain, and (3) cell-surface and intracellular signaling mechanisms
      that are known to regulate axonal branching. The conclusion is that relatively
      little is known about collateral sprouting in adult mammals after spinal cord
      injury but that it may contribute to spontaneous functional motor recovery and
      causes sensory dysfunction. There is some promising data in rodents that
      collateral sprouting can be modulated for improved function, but the
      applicability to primates and relevance to human spinal cord injury remains to be
      determined.

PMID- 16629617
TI  - New insights into neuronal regeneration: the role of axonal protein synthesis in
      pathfinding and axonal extension.
AB  - Protein synthesis in dendrites has become an accepted cellular mechanism that
      contributes to activity-dependent responses in the post-synaptic neuron. Although
      it was argued that protein synthesis does not occur in axons, early studies from
      a number of groups provided evidence for the presence of RNAs and active protein
      synthesis machinery in both invertebrate and vertebrate axons. Work over the past
      decade has confirmed these early findings and has proven the capability of axons
      to locally synthesize some of their own proteins. The functional significance of
      this localized protein synthesis remained largely unknown until recent years.
      Recent studies have shown that mRNA translation in developing and mature axons
      plays a role in axonal growth. In developing axons, protein synthesis allows the
      distal axon to autonomously respond to guidance cues by rapidly changing its
      direction of outgrowth. In addition, local proteolysis of axonal proteins
      contributes axonal guidance and growth cone initiation. This local synthesis and
      degradation of proteins are likely to provide novel insights into how growing
      axons navigate through their complex environment. In mature axons, injury
      triggers formation of a growth cone through localized protein synthesis, and
      moreover, in these injured axons locally synthesized proteins provide a
      retrogradely transported signal that can enhance regenerative responses. The
      intrinsic capability for axons to autonomously regulate local protein levels can
      be modulated by exogenous stimuli providing opportunities for enhancing
      regeneration. In this review, the concept of axonal protein synthesis is
      discussed from a historical perspective. Further, the implications of axonal
      protein synthesis and proteolysis for neural repair are considered.

PMID- 16629618
TI  - Targeting Rho to stimulate repair after spinal cord injury.
AB  - Rho is an important signaling target to promote repair following spinal cord
      injury (SCI). Myelin-derived inhibitory proteins, as well as other classes of
      known growth inhibitory proteins, block regeneration by signaling activation of
      Rho. Here, we review the molecular mechanisms of Rho activation after SCI and
      explain known Rho signaling antagonists. We review the data on use of Rho
      antagonists to promote axon regeneration, neuroprotection, and functional
      recovery after SCI. We report on efforts to translate the nonclincal studies on
      rodents to clinical trials in patients with acute SCI.

PMID- 16629619
TI  - Pharmacological approaches to repair the injured spinal cord.
AB  - Acute traumatic spinal cord injury (SCI) results in a devastating loss of
      neurological function below the level of injury and adversely affects multiple
      systems within the body. The pathobiology of SCI involves a primary mechanical
      insult to the spinal cord and activation of a delayed secondary cascade of
      events, which ultimately causes progressive degeneration of the spinal cord.
      Whereas cell death from the mechanical injury is predominated by necrosis,
      secondary injury events trigger a continuum of necrotic and apoptotic cell death
      mechanisms. These secondary events include vascular abnormalities, ischemia
      reperfusion, glutamate excitotoxicity and disturbances in ionic homeostasis,
      oxidative cell injury, and a robust inflammatory response. No gold standard
      therapy for SCI has been established, although clinical trials with
      methylprednisolone (NASCIS II and III) and GM-1 ganglioside (Maryland and Sygen)
      have demonstrated modest, albeit potentially important therapeutic benefits. In
      light of the overwhelming impact of SCI on the individual, other therapeutic
      interventions are urgently needed. A number of promising pharmacological
      therapies are currently under investigation for neuroprotective abilities in
      animal models of SCI. These include the sodium (Na+) channel blocker riluzole,
      the tetracycline derivative minocycline, the fusogen copolymer polyethylene
      glycol (PEG), and the tissue-protective hormone erythropoietin (EPO). Moreover,
      clinical trials investigating the putative neuroprotective and neuroregenerative
      properties ascribed to the Rho pathway antagonist, Cethrin (BioAxone Therapeutic,
      Inc.), and implantation of activated autologous macrophages (ProCord; Proneuron
      Biotechnologies) in patients with thoracic and cervical SCI are now underway. We
      anticipate that these studies will harken an era of renewed interest in
      translational clinical trials. Ultimately, due to the multi-factorial
      pathophysiology of traumatic SCI, effective therapies will require combined
      approaches.

PMID- 16629620
TI  - Inflammatory and apoptotic signaling after spinal cord injury.
AB  - Central nervous system (CNS) destruction in spinal cord injury (SCI) is caused by
      a complex series of cellular and molecular events. Recent studies have
      concentrated on signaling by receptors in the tumor necrosis factor receptor
      (TNFR) superfamily that mediate diverse biological outcomes ranging from
      inflammation to apoptosis. From the perspective of basic science research,
      understanding how receptor signaling mediates these divergent responses is
      critical in clarifying events underlying irreversible cell injury in clinically
      relevant models of SCI. From a clinical perspective, this work also provides
      novel targets for the development of therapeutic agents that have the potential
      to protect the spinal cord from irreversible damage and promote functional
      recovery. In this review, we discuss how the formation of alternate signaling
      complexes and receptor membrane localization after SCI can influence life and
      death decisions of cells stimulated through two members of the TNFR superfamily,
      Fas/CD95 and TNFR1.

PMID- 16629621
TI  - Demyelination and remyelination after spinal cord injury.
AB  - Since the discovery in the 1960s that remyelination can occur in the damaged
      central nervous system (CNS) (Bunge et al. 1961), there has been much progress in
      understanding the cellular and molecular biology of oligodendroglia and the
      factors that regulate their propagation, migration, differentiation, maturation,
      and ability to myelinate nerve axons. More recently, greater understanding of
      disease states and the role of oligodendrocytes in remyelination have sparked
      tremendous interest in this once obscure field. Although the explosion of
      information is being hampered by adherence to commonly held beliefs based on
      empirical evidence, novel molecular and cellular tools are allowing scientists to
      address age-old assumptions. It is now recognized that, as well as promoting
      salutatory conduction along axons, oligodendroglia are important near-term
      clinical targets for restoring function after CNS injury, particularly spinal
      cord injury. Thus, remyelination appears to be one of the most feasible
      restoration strategies. This review focuses on concepts that are important for
      developing strategies of repair. The brightest young scientists will be attracted
      into this exciting field by its near-term potential for human application.

PMID- 16629622
TI  - Immune-based therapy for spinal cord repair: autologous macrophages and beyond.
AB  - Spinal cord injury is a devastating condition of the central nervous system
      (CNS), often resulting in severe loss of tissue, functional impairment, and only
      limited repair. Studies over the last few years have shown that response to the
      insult and spontaneous attempts at repair are multiphasic processes, with varying
      and sometimes conflicting requirements. This knowledge has led to novel
      strategies of therapeutic intervention. Our view is that a pivotal role in
      repair, maintenance, healing, and cell renewal in the CNS, as in other tissues,
      is played by the immune system. The mode and timing of intervention must be
      carefully selected, however, as the capacity of the CNS to tolerate local repair
      mechanisms is limited. Studies have shown that the spontaneously evoked early
      innate response to CNS injury is characterized by invasion of neutrophils and is
      unfavorable for cell survival. This is followed by a response of the resident
      innate immune cells (microglia), which however cannot supply all the needs of the
      damaged tissue; moreover, once evoked, and for as long as the damage persists,
      the microglial response remains beyond the capacity of the CNS to tolerate it.
      Immune-based clinical intervention is most effective in improving functional and
      morphological recovery when delayed for a certain period. Effective intervention
      might be in the form of (1) local injection of "alternatively activated"
      macrophages, (2) systemic injection of dendritic cells specific to CNS antigens,
      or (3) T-cell-based vaccination. The treatment of choice depends on the severity
      of the insult, the site of injury, the therapeutic window, and safety
      considerations.

PMID- 16629623
TI  - Overcoming inhibition in the damaged spinal cord.
AB  - Inhibition by several inhibitory molecules on oligodendrocytes, and by
      chondroitin sulphate proteoglycans and semaphorins in the glial scar discourages
      regeneration of axons in the injured spinal cord. This inhibition is compounded
      by the poor regenerative ability of most central nervous system (CNS) axons.
      Treatments that block some of these inhibitory mechanisms promote regeneration in
      animal models of cord injury. Plasticity is also reduced by some of the
      inhibitory molecules, and some of the treatments that promote regeneration also
      promote plasticity. This is probably a more achievable therapeutic target than
      axon regeneration, and an effective treatment would be of assistance to the
      majority of patients with partial cord injuries.

PMID- 16629624
TI  - Nogo in the injured spinal cord.
AB  - Myelin of the adult mammalian central nervous system (CNS) has been attributed to
      suppress structural plasticity and to impede regenerating nerve fibers. Nogo-A is
      possibly the best characterized of a variety of neurite growth inhibitors present
      in CNS myelin. Neutralizing its activity results in improved axon regrowth and
      functional recovery in experimental CNS lesion models of adult rodents and
      primates. While Nogo-A has become a major target for therapeutic intervention to
      promote axon regeneration in the CNS, it is realized that such an approach will
      likely have to be combined with other therapeutic strategies to maximize
      functional recovery after spinal cord injury (SCI).

PMID- 16629625
TI  - Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries
      and by adult microglia in vitro.
AB  - Spinal cord scar tissue presents a combined physical and molecular barrier to
      axon regeneration. Theoretically, spinal cord injuries (SCIs) can be rendered
      more permissive to axon growth by either suppressing synthesis of misaligned,
      fibrotic scar tissue and associated axon growth inhibitors, or enzymatically
      degrading them. We have previously shown that acute infusion of human recombinant
      decorin core protein into discreet stab injuries of the rat dorsal column
      pathways effected a major suppression of inflammation, astrogliosis, and multiple
      axon growth inhibitory chondroitin sulfate proteoglycans, which combined to
      promote rapid axon growth across the injury site. The high efficiency of
      chondroitin sulfate proteoglycan (CSPG) core protein suppression (approximately
      90%) suggested that decorin may promote CSPG degradation in addition to
      suppressing CSPG synthesis. As the serine protease plasmin can degrade axon
      growth inhibitory CSPGs (neurocan and phosphacan) and its zymogen, plasmininogen
      is synthesized by microglia, we have investigated whether decorin treatment of
      acute SCIs and cultured adult spinal cord microglia can increase plasminogen/
      plasmin synthesis. Infusion of hr-decorin over the first 8 days post-SCI induced
      10- and 17-fold increases in plasminogen and plasmin protein levels,
      respectively, within sites of injury and a threefold increase in microglial
      plasminogen mRNA in vitro. In addition to potentially degrading multiple axon
      growth inhibitory components of the glial scar, plasmin is known to play major
      roles in activating neurotrophins and promoting central nervous system (CNS)
      plasticity. The wider implications of decorin induction of plasmin in the injured
      spinal cord for axon regeneration, and recovery of function at acute and chronic
      time points post-SCI are reviewed.

PMID- 16629626
TI  - Chemorepellent axon guidance molecules in spinal cord injury.
AB  - Regenerating axons stop growing when they reach the border of the glial-fibrotic
      scar, presumably because they encounter a potent molecular barrier inhibiting
      growth cone advance. Chemorepulsive axon guidance molecules provide a non
      permissive environment restricting and channeling axon growth in the developing
      nervous system. These molecules could also act as growth-inhibitory molecules in
      the regenerating nervous system. The receptors for repulsive guidance cues are
      expressed in the mature nervous system, suggesting that adult neurons are
      sensitive to the activity of developmentally active repulsive proteins. In this
      review, we summarize recent observations on semaphorins, ephrins, and slits in
      the injured brain and spinal cord, providing evidence that these proteins are
      major players in inhibiting axonal regeneration and establishing the glial
      fibrotic scar.

PMID- 16629627
TI  - Collagen matrix in spinal cord injury.
AB  - The fibrous scar that develops after central nervous system (CNS) injury is
      considered a major impediment for axonal regeneration. It consists of a dense
      collagen IV meshwork, which serves as a binding matrix for numerous other
      extracellular matrix components and inhibitory molecules like proteoglycans and
      semaphorins, but also growth-promoting factors. Inhibition of collagen matrix
      formation in brain and spinal cord lesions leads to axonal regeneration and
      functional recovery, although collagen IV per se is not inhibitory for axonal
      outgrowth. This review focuses on the molecular properties of the collagen IV
      matrix and its interactions with various molecules that are expressed after CNS
      lesion. Moreover, studies on collagen expression and matrix formation after
      injury of regenerating versus non-regenerating nervous systems are reviewed.
      Major differences in collagen deposition in the CNS and the peripheral nervous
      system (PNS) and differences in specific cell responses to extracellular matrix
      deposition in the lesion area are discussed. Therapeutic treatments aiming at
      suppression of fibrous scarring have been shown to promote axon regeneration in
      various lesion paradigms of the mammalian CNS.

PMID- 16629628
TI  - Designing cell- and gene-based regeneration strategies to repair the injured
      spinal cord.
AB  - There is an array of new and promising strategies being developed to improve
      function after spinal cord injury (SCI). The targeting of a diversity of
      deleterious processes within the tissue after SCI will necessitate a multi
      factorial intervention, such as the combination of cell- and gene-based
      approaches. To ensure proper development and design of these experiments, many
      issues need to be addressed. It is the purpose of this review to consider the
      strategies involved in testing the efficacy of these new combinations to improve
      axonal regeneration. For cell-based therapy, issues are choosing a SCI model, the
      time of cell implantation, placement of cells and their subsequent migration,
      fluid versus solid grafts, use of agents to prevent immune rejection, and
      tracking of implanted cells. Grafting is also discussed in view of improving
      function, reducing secondary damage, bridging the injured spinal cord, supporting
      axonal regrowth, replacing lost neurons, facilitating myelination, and promoting
      axonal growth from the implant into the cord. The choice of a gene delivery
      system, gene-based therapies in vivo to provide chemoattractant and guidance
      cues, altering the intrinsic regenerative capacity of neurons, enhancing
      endogenous non-neuronal cell functions, and targeting the synthesis of growth
      inhibitory molecules are also discussed, as well as combining ex vivo gene and
      cell therapies.

PMID- 16629629
TI  - Schwann cell transplantation for repair of the adult spinal cord.
AB  - The Schwann cell is one of the most widely studied cell types for repair of the
      spinal cord. These cells play a crucial role in endogenous repair of peripheral
      nerves due to their ability to dedifferentiate, migrate, proliferate, express
      growth promoting factors, and myelinate regenerating axons. Following trauma to
      the spinal cord, Schwann cells migrate from the periphery into the injury site,
      where they apparently participate in endogenous repair processes. For
      transplantation into the spinal cord, large numbers of Schwann cells are
      necessary to fill injury-induced cystic cavities. Several culture systems have
      been developed that provide large, highly purified populations of Schwann cells.
      Importantly, the development of in vitro systems to harvest human Schwann cells
      presents a unique opportunity for autologous transplantation in the clinic. In
      animal models of spinal cord injury (SCI), grafting Schwann cells or peripheral
      nerve into the lesion site has been shown to promote axonal regeneration and
      myelination. However, axons do not regenerate beyond the transplant due to the
      inhibitory nature of the glial scar surrounding the injury. To overcome the glial
      scar inhibition, additional approaches such as increasing the intrinsic capacity
      of axons to regenerate and/or removal of the inhibitory molecules associated with
      reactive astrocytes and/or oligodendrocyte myelin should be incorporated.
      Clearly, Schwann cells have great potential for repair of the injured spinal
      cord, but they need to be combined with other interventions to maximize axonal
      regeneration and functional recovery.

PMID- 16629630
TI  - Olfactory ensheathing cells: characteristics, genetic engineering, and
      therapeutic potential.
AB  - Injured neurons in the mammalian central nervous system (CNS) do not normally
      regenerate their axons after injury. Neurotrauma to the CNS usually results in
      axonal damage and subsequent loss of communication between neuronal networks,
      causing long-term functional deficits. For CNS regeneration, repair strategies
      need to be developed that promote regrowth of lesioned axon projections and
      restoration of neuronal connectivity. After spinal cord injury (SCI), cystic
      cavitations are often found, particularly in the later stages, due to the loss of
      neural tissue at the original impact site. Ultimately, for the promotion of
      axonal regrowth in these situations, some form of transplantation will be
      required to provide lesioned axons with a supportive substrate along which they
      can extend. Here, we review the use of olfactory ensheathing cells: their
      location and role in the olfactory system, their use as cellular transplants in
      SCI paradigms, alone or in combination with gene therapy, and the unique
      properties of these cells that may give them a potential advantage over other
      cellular transplants.

PMID- 16629631
TI  - Functional considerations of stem cell transplantation therapy for spinal cord
      repair.
AB  - Stem cells hold great promise for therapeutic repair after spinal cord injury
      (SCI). This review compares the current experimental approaches taken towards a
      stem cell-based therapy for SCI. It critically evaluates stem cell sources,
      injury paradigms, and functional measurements applied to detect behavioral
      changes after transplantation into the spinal cord. Many of the documented
      improvements do not exclusively depend on lineage-specific cellular
      differentiation. In most of the studies, the functional tests used cannot
      unequivocally demonstrate how differentiation of the transplanted cells
      contributes to the observed effects. Standardized cell isolation and
      transplantation protocols could facilitate the assessment of the true
      contribution of various experimental parameters on recovery. We conclude that at
      present embryonic stem (ES)-derived cells hold the most promise for therapeutic
      utility, but that non-neural cells may ultimately be optimal if the mechanism of
      possible transdifferentiation can be elucidated.

PMID- 16629632
TI  - Bioengineered strategies for spinal cord repair.
AB  - This article reviews bioengineered strategies for spinal cord repair using tissue
      engineered scaffolds and drug delivery systems. The pathophysiology of spinal
      cord injury (SCI) is multifactorial and multiphasic, and therefore, it is likely
      that effective treatments will require combinations of strategies such as
      neuroprotection to counteract secondary injury, provision of scaffolds to replace
      lost tissue, and methods to enhance axonal regrowth, synaptic plasticity, and
      inhibition of astrocytosis. Biomaterials have major advantages for spinal cord
      repair because of their structural and chemical versatility. To date, various
      degradable or non-degradable biomaterial polymers have been tested as guidance
      channels or delivery systems for cellular and non-cellular neuroprotective or
      neuroregenerative agents in experimental SCI. There is promise that
      bioengineering technology utilizing cellular treatment strategies, including
      Schwann cells, olfactory ensheathing glia, or neural stem cells, can promote
      repair of the injured spinal cord. This review is divided into three parts: (1)
      degradable and non-degradable biomaterials; (2) device design; and (3)
      combination strategies with scaffolds. We will show that bioengineering
      combinations of cellular and non-cellular strategies have enhanced the potential
      for experimental SCI repair, although further pre-clinical work is required
      before this technology can be translated to humans.

PMID- 16629633
TI  - Direct gene therapy for repair of the spinal cord.
AB  - For regrowth of injured nerve fibers following spinal cord injury (SCI), the
      environment must be favorable for axonal growth. The delivery of a therapeutic
      gene, beneficial for axonal growth, into the central nervous system for repair
      can be accomplished in many ways. Perhaps the most simple and elegant strategy is
      the so-called direct gene therapy approach that uses a single injection for
      delivery of a gene therapy vehicle. Among the vectors that have been used to
      transduce neural tissue in vivo are non-viral, herpes simplex viral, adeno
      associated viral, adenoviral, and lentiviral vectors, each with their own merits
      and limitations. Many studies have been undertaken using direct gene therapy,
      ranging from strategies for neuroprotection to axonal growth promotion at the
      injury site, dorsal root injury repair, and initiation of a growth-supporting
      genetic program. The limitations and successes of direct gene transfer for spinal
      cord repair are discussed in this review.

PMID- 16629634
TI  - Long-term care of paraplegic laboratory mammals.
AB  - Repair of spinal cord injuries (SCIs) is still a major clinical challenge.
      Several attempts have been made to find a cure for this condition in experimental
      animals that could be extrapolated to humans. A key for success seems the
      availability of optimum animal models for testing different therapies. Complete
      spinal cord lesion in mammals is considered the most accurate injury model. In
      addition, long-term survival of animals seems more appropriate, as this increases
      the efficacy of the repair strategies. However, paraplegic animals require
      special care and treatment for proper longterm maintenance, and to date, there
      are no published protocols. This lack of available information has discouraged
      scientists from working with this injury model. Over the past 7 years, we have
      tested the repair efficacy of olfactory ensheathing glia in paraplegic rats for
      survival periods of more than 8 months. To keep these animals healthy for this
      long time, we adapted and administered treatments used in people with paraplegia.
      These same protocols (developed for rodents in our group) are being applied to
      paraplegic monkeys. In this review, we provide an overview of the proper handling
      and care of paraplegic adult laboratory mammals for long periods. This
      information might help other groups to optimize the outcome obtained and to
      better evaluate the prospect of a given experimental repair strategy. In
      addition, the use of human treatments in paraplegic animals provides a more
      realistic model for a later transfer to the clinical arena.

PMID- 16629635
TI  - CatWalk-assisted gait analysis in the assessment of spinal cord injury.
AB  - Gait analysis plays an important role in the assessment of neurological function
      in many disease models. In this review, we focus on the newly developed CatWalk
      system for gait analysis. CatWalk was originally developed as a tool to enhance
      assessment of functional outcome in spinal cord injury (SCI) models. Although it
      is also of value in models of among others (neuropathic) pain and peripheral
      nerve damage, we will limit ourselves to its use in SCI models in this review.
      The system is positioned against well-established locomotor function tests, and
      it is indicated how CatWalk can enhance the usefulness of such tests. Development
      of the system started with the idea that it should enable objective assessment of
      coordination, and powerful measures of coordination are nowadays included in the
      analysis options provided by CatWalk. Therefore, a major part of this review is
      devoted to the history and meaning of these coordination measures.

PMID- 16629636
TI  - Cell and molecular approaches to the attenuation of pain after spinal cord
      injury.
AB  - Recent experimental research to treat spinal cord injury (SCI) pain has greatly
      increased our understanding of how such chronic pain might be modulated in the
      human population. Neuropathic pain is caused by the structural and biochemical
      changes associated with the peripheral and central nervous system damage
      associated with nervous system trauma, often leading to an imbalance in
      endogenous excitatory and inhibitory spinal systems that modulate sensory
      processing. But current pharmacological therapies are often ineffective over time
      for the greater number of patients. Although there are a variety of useful
      surgical and pharmacologic interventions (including electric stimulation,
      implantable mechanical pumps and a myriad of drugs for pain relief) cell and
      molecular technologies are a new frontier in pain medicine. These other potential
      therapeutic agents of pain are based on current and developing treatment
      strategies elucidated from recent research, especially concerning central spinal
      sensitization, and the spinal mechanisms that are thought to be the origin and
      ongoing cause of chronic pain, even when the injury is peripheral in location.
      Newly developing translational strategies such as molecular agents, viral
      mediated gene transfer or cellular transplants to treat chronic pain are being
      evaluated in a variety of peripheral and central injury models. They seek to
      address both the causes of neuropathic pain, to interfere with its development
      and maintenance over time, and give the injured person with pain an improved
      quality-of-life that allows them to better deal with the larger tasks of daily
      life and the strenuous rehabilitation that might also improve motor function
      after SCI.

PMID- 16629637
TI  - Rehabilitative therapies after spinal cord injury.
AB  - We review some basic and highly relevant concepts in the effort to develop
      improved rehabilitative interventions for subjects with spinal cord injury (SCI).
      Interventions that are likely to contribute to improved sensorimotor function
      include (1) practice of the specific motor task that needs to be improved; and
      (2) combining the training with one or more interventions--such as
      pharmacological modulation of the excitability of spinal neural networks,
      implantation of selected cell types such as olfactory ensheathing glia (OEG),
      and/or modulation of the excitability of the spinal cord via epidural
      stimulation. Upon improvement of the neural control of the musculature following
      SCI, it will always be prudent to maximize the torque output from these
      activation patterns by assuring that muscle mass is maintained. Therefore, it
      seems quite feasible that considerable improvement in locomotor performance can
      be achieved by improved coordination of motor pools, as well as effective
      recovery of muscle mass, which will assist in the potential generation of normal
      forces among agonistic and antagonistic muscle groups.

PMID- 16629638
TI  - Physical determinants, emerging concepts, and training approaches in gait of
      individuals with spinal cord injury.
AB  - The aim of this review is to examine the physical determinants for functional
      walking as well as the efficacy of gait rehabilitation after spinal cord injury
      (SCI) in humans. The results indicate several important physical determinants in
      gait. Examples are provided of different interventions that produce beneficial
      effects on outcome measures of gait such as gait speed, stride length, walking
      endurance, motor recovery, and gait quality. These findings need to be considered
      in current SCI rehabilitation practices, but the efficacy of certain
      interventions remains unclear. Well-designed clinical trials are needed to
      provide evidence of the role of physical determinants in the development of new
      concepts and principles in locomotor recovery after SCI. This review focuses on
      relevant literature, and informs rehabilitation specialists and basic scientists
      about the physical determinants and factors to consider for optimization of gait
      training in individuals with incomplete SCI.

PMID- 16629639
TI  - Clinical trials in spinal cord injury.
AB  - Progress in promoting axonal plasticity and regeneration in animal models of
      spinal cord injury (SCI) has led to novel prospects for the initiation of human
      clinical trials in the near future. This review discusses a number of
      considerations in the path to translating a preclinical candidate from the
      laboratory to clinical testing. We will also briefly discuss issues associated
      with the design, performance, analysis, and reporting of human clinical trials in
      SCI. It is important, for both the medical community and the spinal cord injured
      community, that objective scientific and medical standards are adopted in the
      clinical translation of potentially promising, but as yet unproven, therapies for
      SCI.

PMID- 16629640
TI  - Evidence for allosteric regulation of pH-sensitive System A (SNAT2) and System N
      (SNAT5) amino acid transporter activity involving a conserved histidine residue.
AB  - System A and N amino acid transporters are key effectors of movement of amino
      acids across the plasma membrane of mammalian cells. These Na+-dependent
      transporters of the SLC38 gene family are highly sensitive to changes in pH
      within the physiological range, with transport markedly depressed at pH 7.0. We
      have investigated the possible role of histidine residues in the transporter
      proteins in determining this pH-sensitivity. The histidine-modifying agent DEPC
      (diethyl pyrocarbonate) markedly reduces the pH-sensitivity of SNAT2 and SNAT5
      transporters (representative isoforms of System A and N respectively,
      overexpressed in Xenopus oocytes) in a concentration-dependent manner but does
      not completely inactivate transport activity. These effects of DEPC were reversed
      by hydroxylamine and partially blocked in the presence of excess amino acid
      substrate. DEPC treatment also blocked a reduction in apparent affinity for Na+
      (K0.5Na+) of the SNAT2 transporter at low external pH. Mutation of the highly
      conserved C-terminal histidine residue to alanine in either SNAT2 (H504A) or
      SNAT5 (H471A) produced a transport phenotype exhibiting reduced, DEPC-resistant
      pH-sensitivity with no change in K0.5Na+ at low external pH. We suggest that the
      pH-sensitivity of these structurally related transporters results at least partly
      from a common allosteric mechanism influencing Na+ binding, which involves an H+
      modifier site associated with C-terminal histidine residues.

PMID- 16629641
TI  - Definition and management of anemia in patients infected with hepatitis C virus.
AB  - Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis,
      hepatocellular carcinoma, and end-stage liver disease. The current best treatment
      for HCV infection is combination therapy with pegylated interferon and ribavirin.
      Although this regimen produces sustained virologic responses (SVRs) in
      approximately 50% of patients, it can be associated with a potentially dose
      limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result
      of ribavirin-induced hemolysis, and this anemia can be problematic in patients
      with HCV infection, especially those who have comorbid renal or cardiovascular
      disorders. In general, anemia can increase the risk of morbidity and mortality,
      and may have negative effects on cerebral function and quality of life. Although
      ribavirin-associated anemia can be reversed by dose reduction or discontinuation,
      this approach compromises outcomes by significantly decreasing SVR rates.
      Recombinant human erythropoietin has been used to manage ribavirin-associated
      anemia but has other potential disadvantages. Viramidine, a liver-targeting
      prodrug of ribavirin, has the potential to maintain the virologic efficacy of
      ribavirin while decreasing the risk of hemolytic anemia in patients with chronic
      hepatitis C.

PMID- 16629642
TI  - Peg-interferon improves liver histology in patients with HBeAg-positive chronic
      hepatitis B: no additional benefit of combination with lamivudine.
AB  - BACKGROUND: The effect of pegylated interferon or its combination with lamivudine
      on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a
      double-blinded, randomized, multi-center study we assessed histological changes
      in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks
      with Pegylated interferon alpha-2b (PEG-IFN) in combination with either
      lamivudine or placebo. Liver biopsies were taken before and at the end of
      treatment. All biopsies were blinded and scored according to the Ishak system.
      RESULTS: Necroinflammatory score improved (defined as a decrease of at least two
      points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group
      and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score
      improved (decrease of at least 1 point) in 17 patients (33%) of the combination
      therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23).
      Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed
      a larger decline in necroinflammatory score than non-responders (mean decline 2.3
      and 1.2 points, respectively, P=0.02). Among patients receiving PEG-IFN
      monotherapy necroinflammation improved more frequently in responders (78% of
      responders vs. 43% of non-responders, P=0.01) and in patients who showed
      normalization of ALT (76% of patients with normal ALT vs. 40% of patients with
      abnormal ALT, P=0.01). Fibrosis score in the PEG-IFN monotherapy group improved
      more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG
      IFN/lamivudine combination therapy group, we found no significant association
      between virological and biochemical endpoints and histological improvement.
      CONCLUSIONS: Treatment with PEG-IFN therapy improves liver necroinflammation in
      HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also
      improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not
      further improve the histological outcome.

PMID- 16629643
TI  - PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.
AB  - BACKGROUND: Autoantibody responses reactive with the E2 and E3BP components of
      pyruvate dehydrogenase complex (PDC), which characterise primary biliary
      cirrhosis (PBC) crossreact, precluding the identification, from serological
      studies, of the antigen to which the principal breakdown of tolerance occurs.
      Although autoreactive T-cell responses to PDC-E2 have been well characterised it
      is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC
      E3BP. The aims of this study were to characterise autoreactive T-cell responses
      to PDC-E3BP in PBC and potential factors regulating their expression. METHODS:
      Peripheral blood T-cell proliferative responses to purified recombinant human PDC
      E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients
      and control subjects. RESULTS: T-cell proliferative responses to both E2 and E3BP
      were absent from control subjects (median peak stimulation index (SI) to PDC-E2
      1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7
      2.1]], 0/10 positive). Significant responses to PDC-E2 were seen in the majority
      of patients (median peak SI 11.4 [0.4-24.4], 17/20 (85%) positive) but to PDC
      E3BP in only a minority (median peak SI 1-9 [0.6-9.95], 8/20 (40%) positive).
      Where responses to PDC-E3BP were seen they were universally secondary to
      responses to PDC-E2. CONCLUSIONS: Despite the presence of antibodies reactive
      with PDC-E3BP in the majority of PBC patients this self-protein is not a dominant
      T-cell autoantigen in PBC.

PMID- 16629644
TI  - Expression pattern of angiogenic factors and prognosis after hepatic resection in
      hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor
      1 alpha.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a hypervascular tumor and
      angiogenesis plays an important role in its progression. Angiogenesis is
      regulated by a balance between pro and antiangiogenic molecules. The aim of this
      study was to investigate the expressions of angiogenic factors and elucidate
      their roles in angiogenesis in HCC. METHODS: We investigated immunohistochemical
      expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and
      Ang-2), hypoxia-induced factor-1alpha (HIF-1alpha) and thrombospondin-1 (TSP-1)
      in 60 specimens of surgically resected HCC. We investigated the relationship
      between their expressions and clinicopathological factors or prognosis. RESULTS:
      Ang-2 staining had a significant correlation with the grade of differentiation of
      HCC cells (P=0.0082). VEGF and Ang-2 expression correlated positively with
      microvessel density (MVD) (P=0.0061 and 0.0374, respectively). MVD of well
      differentiated HCC were significantly lower than those of moderately and poorly
      differentiated HCC. The disease-free survival time of patients with high Ang-2
      and/or HIF-1alpha expression was significantly shorter than that of the low
      expression group (P=0.0278 and 0.0374, respectively). CONCLUSION: Our study
      showed that the expression of VEGF and Ang-2 correlated with MVD. Strong Ang-2
      expression and/or high nuclear expression of HIF-1alpha is a significant
      predictive factor for recurrence after curative resection in HCC patients.

PMID- 16629645
TI  - Novel markers of cell kinetics to evaluate progression from cirrhosis to
      hepatocellular carcinoma.
AB  - BACKGROUND: We investigated cell cycle kinetics of nodular lesions in cirrhosis
      to differentiate hepatocellular carcinoma (HCC) from its precursor lesions.
      METHODS: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN),
      and five dysplastic nodules (DN), identified in explant cirrhotic livers of five
      consecutive patients transplanted at Royal Free Hospital in 2002.
      Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of
      positive cells counted. RESULTS: The proportion of cells expressing MCM2 was more
      than those expressing Ki67, which in turn was more than those expressing geminin
      (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a
      statistically significant trend of increasing Ki67 expression (P=0.006), from RN
      to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2
      (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in
      LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four
      different cell kinetics patterns: 'resting' (G0 cells: MCM2 -ve, Ki67 -ve,
      geminin -ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1
      phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve,
      Ki67 +ve, geminin +ve) nodules. CONCLUSIONS: The combination of MCM2, geminin and
      Ki67 could represent a valuable tool in the understanding of HCC progression in
      cirrhosis.

PMID- 16629646
TI  - Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A
      single centre experience.
AB  - BACKGROUND: Hepatocellular adenomas (HCA) may present with spontaneous
      haemorrhage and rupture. The aim of this study was to assess management in 22
      patients treated for haemorrhage and/or rupture of HCA. PATIENTS AND METHODS:
      Between May 1990 and July 2005, 22 female patients were diagnosed with acute
      haemorrhage and/or rupture of lesions highly suspicious of HCA. Preoperative
      imaging diagnostics and pathologic specimens were reviewed. RESULTS: Twelve
      haemodynamically stable and four unstable patients could be treated
      conservatively. One patient underwent acute partial liver resection, whereas four
      patients underwent laparotomy with initial packing of the liver. In one patient,
      selective embolisation of the left hepatic artery was performed. Fifteen patients
      eventually underwent resection after a mean time of 8 months after initial
      treatment. Six patients did not undergo resection and showed no complications or
      rebleeding after a mean follow-up of 24.6 months. Only in seven patients,
      histopathological examination showed HCA, and in one patient, HCA with focal
      nodular hyperplasia. CONCLUSION: HCA with haemorrhage and/or rupture does not
      necessarily require immediate liver resection. Conservative treatment is
      justified in stable patients. In case of an instable patient with or without
      hemoperitoneum, laparotomy with packing or selective embolisation can stop the
      bleeding.

PMID- 16629647
TI  - Hyaluronic acid and aspartate aminotransferase levels normalized by liver
      function can reflect sinusoidal impairment in chronic liver disease.
AB  - BACKGROUND/AIM: To evaluate the relationship between hyaluronic acid/aminopyrine
      breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between
      HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end
      stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate
      aminotransferase (AST)/ABT in relation to the HA/ABT. METHODS: We studied 48
      patients with histologically proven chronic hepatitis C (CHC) and 35 patients
      with compensated cirrhosis (CIR). RESULTS: HA/ABT and AST/ABT showed a more
      significant correlation with the fibrosis score than HA or ABT or AST alone in
      the 48 CHC patients: r=0.568 (P<0.0001), r=0.610 (P<0.0001), r=0.450 (P=0.0021),
      r=-0.449 (P=0.0021), and r=0.472(P=0.0012), respectively. Progressive liver
      damage (fibrosis 1-2 vs fibrosis 3-6 vs cirrhosis) was significantly (P<0.05)
      reflected by both HA/ABT (mean+/-SEM: 4.0+/-0.9 vs 18.1+/-4.2 vs 149.9+/-33.1)
      and AST/ABT (6.3+/-1.8 vs 12.7+/-1.6 vs 42.1+/-14.6). A strong relationship was
      found between HA/ABT and AST/ABT (r=0.755 P<0.0001). In cirrhotic patients, the
      most significant relationship was observed between HA/ABT and CTP r=0.483 and
      P=0.0049, and MELD r=0.523 and P=0.0023. CONCLUSION: Considering that HA levels
      in chronic hepatitis depend on the progressive impairment of sinusoidal
      endothelial cells (SEC), related to progressive fibrosis, HA/ABT ratio would seem
      to be the most specific reflection of progressive impairment of the SEC. AST/ABT
      could be used as a possible surrogate of HA in identifying SEC impairment in
      chronic hepatitis.

PMID- 16629648
TI  - Re-evaluation of serum alanine aminotransferase upper normal limit and its
      modulating factors in a large-scale population study.
AB  - BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT)
      normal range was recently challenged, because patients diagnosed with liver
      diseases may have 'normal' or near-'normal' ALT levels, and because possible
      modulators are often ignored in determining normal range. AIM: To estimate the
      ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We
      reviewed medical records of subjects aged 15-90, who underwent standard panels of
      laboratory tests, including serum ALT, over 6 months at a central laboratory.
      Three groups were defined: Group 1, comprised total study population (N=272 273).
      Group 2 (N=87 020) comprised total study population, excluding those receiving
      potentially hepatotoxic drugs, or diagnosed with liver disease, or had any
      abnormal laboratory test results other than for triglycerides, cholesterol,
      glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT
      values we established the new ULN, comprised Group 2 subjects with normal
      triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th
      percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1,
      40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was
      below ULN listed by the test manufacturer (52 U/l), had ALT level above our new
      ULN. Linear and logistic-regression analyses showed that ALT levels were
      significantly modified by gender, age, glucose, cholesterol, triglycerides, and
      overweight/obesity diagnosis. Significant interaction was found between gender,
      glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of
      'healthy' population, serum ALT ULN was far lower than currently accepted value.
      Age and gender may be considered when determining the ULN for ALT.

PMID- 16629649
TI  - Tumor necrosis factor-a antisense transfer remarkably improves hepatic graft
      viability.
AB  - BACKGROUND: Cold ischemia/reperfusion injury of the hepatic graft, an unsolved
      problem in liver transplantations, is attributed to the release of inflammatory
      cytokines, especially the tumor necrosis factor- (TNF) alpha, from activated
      Kupffer cells (KC). Therefore, the specific inhibition of TNF-alpha could improve
      the viability of the hepatic graft upon reperfusion. METHODS: We assessed the
      efficacy of TNF-alpha antisense (TNF-AS) oligodeoxynucleotides (ODNs) delivery to
      KC in a rodent liver transplantation model. RESULTS: Seventy-one percent of the
      animals that received 6 hours preserved grafts in baths of lactated Ringer's
      solution (4 degrees C) and were treated with TNF-AS survived for over 14 days.
      Eighty percent of the animals treated with vehicle, sense ODNs, or balanced salt
      saline (BSS) died. Four hours after reperfusion of the liver, a significant
      reduction was noted in livers treated with TNF-AS in the release of cytosolic
      enzymes from the hepatocytes and the serum TNF-alpha (P<0.05). The expressions of
      TNF-alpha on KC and of intercellular adhesion molecule-1 on sinusoidal
      endothelial cells were completely suppressed in TNF-AS-treated livers.
      CONCLUSIONS: TNF-AS delivery improves the viability of the hepatic graft, and
      this technique may solve hepatic graft nonfunction in a clinical setting.

PMID- 16629650
TI  - Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation
      during experimental cholestatic ductal hyperplasia.
AB  - BACKGROUND: Ductopenia is observed in end-stage human cholestatic diseases. The
      limited capability of cholangiocytes for proliferation is suggested to be the
      principal reason. Recently, bone marrow cells (BMCs) have been reported to behave
      as hepatic stem cells; however, their capability to differentiate into
      cholangiocytes in cholestasis remains unclear. METHODS: Normal mice were lethally
      irradiated to suppress the proliferation of self-BMCs; thereafter, the BMCs from
      enhanced green fluorescent protein (EGFP)-transgenic mice were transferred to
      recipients. Chronic cholestasis was induced by 0.1%alpha-naphtylisothiocyanate
      (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed
      morphologically and immunohistchemically (cytokeratin-7 (CK-7), A6).
      Proliferative activity (proliferating cell nuclear antigen (PCNA) protein
      expression), hepatic growth factor (HGF) receptor (c-Met), stem cell factor
      receptor (c-kit), Notch2 and Hes1 expression were also evaluated. RESULTS: Marked
      cholangiocyte proliferation was observed in ANIT-fed mice. However, no EGFP/CK-7
      double positive cells were identified in any of the liver specimens after BMCs
      transfer (Tx). In hepatic parenchyma, there were scattered EGFP-positive cells,
      although none of them were positive for CK-7. CONCLUSIONS: In spite of the
      significant ductular proliferations after ANIT feeding, no EGFP-positive
      cholangiocytes were confirmed by any other means in this chronic cholestasis
      model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the
      differentiation of cholangiocytes. Future studies are feasible to clarify the
      origin of proliferative cholangiocytes observed in this chronic cholestatic
      ductular hyperplasia model.

PMID- 16629651
TI  - Human intrahepatic biliary epithelial cells function in innate immunity by
      producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways.
AB  - BACKGROUND: Human intrahepatic biliary epithelial cells (HIBECs) may play active
      roles in both the innate and adaptive immune responses. Little is known, however,
      about the role of toll-like receptors (TLRs) on HIBECs in inflammatory
      cholangiopathies. METHODS: The expression of TLR1-9 and the biological responses
      to their ligands, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), were
      studied in cultured HIBECs by reverse transcription-polymerase chain reaction,
      immunoblotting, and enzyme-linked immunosorbent assay. RESULTS: HIBECs
      constitutively expressed transcripts encoding TLR1-6 and 9, as well as myeloid
      differentiation factor 88 (MyD88), MD2, and CD14. Stimulation of HIBECs with LPS
      resulted in translocation of NF-kappaB subunits from the cytoplasmic to the
      nuclear fraction, followed by increased secretion of a variety of
      chemokines/cytokines, including interleukin-8 (IL-8), monocyte chemotactic
      protein-1 (MCP-1), and IL-6. Treatment with BAY11-7082 efficiently inhibited the
      LPS-induced transcription and secretion of these chemokines/cytokines. In HIBECs,
      the mitogen-activated protein kinases (MAPKs) were also activated by LPS
      stimulation. These results indicated that LPS activates HIBECs via a TLR4-MyD88
      dependent pathway. Stimulation of HIBECs with LTA induced the secretion of a
      similar profile of cytokines/chemokines via a TLR2-MyD88-dependent pathway.
      CONCLUSIONS: In HIBECs, at least TLR2 and 4 are capable of mediating innate
      immune system function in vitro. This result, in conjunction with our recent
      finding that TLR4 expression is increased in biliary epithelial cells in primary
      biliary cirrhosis, suggests the involvement of TLRs in the development of chronic
      inflammatory cholangiopathies.

PMID- 16629652
TI  - Relationship between oxidative stress levels and activation state on a hepatic
      stellate cell line.
AB  - BACKGROUND/AIMS: Oxidative stress plays an important role in liver fibrosis.
      Under pathological conditions, hepatic stellate cells (HSC) undergo an activation
      process, developing a myofibroblast-like phenotype from the lipocyte phenotype.
      In this study, we determined the levels of oxidative stress and proliferation in
      different activation states of an experimental model of mouse HSC, the GRX cell
      line. These cells can be induced in vitro to display a more activated state or a
      quiescent phenotype. METHODS/RESULTS: We observed increased oxidative damage and
      higher levels of reactive oxygen species, measured by thiobarbituric acid
      reactive species and 2',7'-dichlorofluorescein diacetate, respectively, and
      diminished catalase activity in activated cells. Activation decreased
      proliferation and increased the number of cells in G2/M. Antioxidants N
      acetylcysteine and Trolox varied in their capacity to correct the oxidative
      stress and proliferation status. CONCLUSIONS: The differences in physiological
      functions of stellate cell phenotypes suggest a relationship between oxidative
      stress levels and activation state.

PMID- 16629653
TI  - Liver protection by hypothermic perfusion at different temperatures during total
      vascular exclusion.
AB  - INTRODUCTION: In situ hypothermic perfusion (HP) can be applied to attenuate
      ischemia and reperfusion (I/R) injury during liver resection under total vascular
      exclusion (TVE). This study examines the protective effect of cooling by HP at 20
      and 28 degrees C as compared with no HP during TVE in a porcine liver I/R model.
      METHODS: Twenty-one pigs underwent 60 min TVE of the liver followed by 24 h
      reperfusion. HP was performed via the portal vein using ringerlactate solution of
      4 degrees C. Pigs were assigned to three groups: TVE without HP (no-HP, n=9), TVE
      with HP at 28 degrees C (HP-28, n=6) and TVE with HP at 20 degrees C (HP-20,
      n=6). RESULTS: Perfusion volumes during TVE were 5.1+/-0.5 and 17.3+/-1.7 l in HP
      28 and HP-20, respectively (P<0.05). Aspartate aminotransferase (AST) after 24 h
      reperfusion was 1172+/-440 U/l in no-HP as compared with 223+/-69 and 180+/-22
      U/l in HP-28 and HP-20, respectively (P<0.05). No differences in liver function
      or histopathology were found between the HP-28 and HP-20 groups. CONCLUSIONS: HP
      at 20 degrees C is equally effective in preserving liver function and preventing
      hepatocellular injury under TVE as compared with HP at 28 degrees C. HP at 28
      degrees C is advised, because of the lesser perfusion volume necessary for
      cooling of the liver.

PMID- 16629654
TI  - Successful liver transplantation and delivery in a woman with fulminant hepatic
      failure occurring during the second trimester of pregnancy.
AB  - BACKGROUND: Severe liver dysfunction occurring during pregnancy is an unusual but
      dramatic event that poses special technical and ethical issues because it
      involves two lives. METHODS AND RESULTS: We report the case of a 35-year-old
      woman with cryptogenic fulminant hepatic failure who underwent successful
      orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively
      uneventful post-operative course she delivered a normal offspring at the 27th
      week of gestation. There were no obstetrical complications and neonatal outcome
      was excellent. After a year of follow-up, the patient is doing well,and the
      newborn has exhibited normal psychomotor and weight/height development.
      CONCLUSION: This case illustrates the challenge of treating fulminant hepatic
      failure during pregnancy and demonstrates that liver transplantation is a
      feasible therapeutic option for treatment of patients with this condition,
      allowing successful completion of pregnancy.

PMID- 16629655
TI  - Salmonellosis with liver abscess mimicking hepatocellular carcinoma in a diabetic
      and cirrhotic patient: a case report and review of the literature.
AB  - Salmonellosis with liver abscess in a cirrhotic liver is extremely rare. We
      report the first case of Salmonellosis with septic shock and liver abscess in a
      diabetic and cirrhotic patient. The image studies of liver initially favored
      hepatocellular carcinoma. But no definite focus of sepsis was found. After close
      follow-up of the liver space-occupied lesion, ultrasound examination revealed the
      features of liver abscesses at space-occupied lesion later. Ultrasound-guided
      liver aspiration proved abscess. The clinical and radiological responses were
      good after antibiotics treatment.

PMID- 16629656
TI  - Gastric ulcer triggered after percutaneous ethanol injection therapy for left
      lobe hepatocellular carcinoma.

PMID- 16629658
TI  - Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c-type
      cytochromes.
AB  - In all organisms, haem is post-translationally and covalently attached to c
      apocytochromes to produce c holocytochromes via a process called c-type
      cytochromes maturation, which involves numerous components. In bacteria it was
      not clear which of these components catalyses the extracytoplasmic haem
      apocytochrome ligation per se. In this issue of Molecular Microbiology, Feissner
      and colleagues report that a single polypeptide from Helicobacter pylori,
      corresponding to the fusion of two proteins found in other organisms, performs
      haem ligation to a coexpressed Bordetella pertussis apocytochrome c in an
      Escherichia coli mutant lacking its own cytochrome c maturation proteins. This
      simple experimental system pinpoints the components catalysing extracytoplasmic
      covalent haem ligation and raises intriguing issues about the requirements for
      delivery of haem and apocytochrome c substrates to produce c holocytochromes.

PMID- 16629659
TI  - Lipid trafficking to the outer membrane of Gram-negative bacteria.
AB  - The envelope of Gram-negative bacteria is composed of two distinct lipid
      membranes: an inner membrane and outer membrane. The outer membrane is an
      asymmetric bilayer with an inner leaflet of phospholipids and an outer leaflet of
      lipopolysaccharide. Most of the steps of lipid synthesis occur within the
      cytoplasmic compartment of the cell. Lipids must then be transported across the
      inner membrane and delivered to the outer membrane. These topological features
      combined with the ability to apply the tools of biochemistry and genetics make
      the Gram-negative envelope a fascinating model for the study of lipid
      trafficking. In addition, as lipopolysaccharide is essential for growth of most
      strains and is a potent inducer of the mammalian innate immune response via
      activation of Toll-like receptors, Gram-negative lipid transport is also a
      promising target for the development of novel antibacterial and anti-inflammatory
      compounds. This review focuses on recent developments in our understanding of
      lipid transport across the inner membrane and to the outer membrane of Gram
      negative bacteria.

PMID- 16629660
TI  - Self-compartmentalized bacterial proteases and pathogenesis.
AB  - Protein degradation is required for homeostasis of all living organisms. Self
      compartmentalized ATP-dependent proteases are required for virulence of several
      pathogenic bacteria. Among the proteases implicated are ClpP and Lon, as well as
      the more recently identified bacterial proteasome. It is generally assumed that
      when a pathogen invades a host, microbial proteins become irreversibly damaged
      and need to be degraded. However, recent data suggest that proteolysis is also
      essential for virulence gene regulation. In this review, we will discuss what is
      known about the relationship between ATP-dependent proteolysis and pathogenesis.
      In addition, we will propose other potential roles these chambered proteases may
      have in bacterial virulence. Importantly, these proteases show promise as targets
      for antimicrobial therapy.

PMID- 16629661
TI  - Recombinant cytochromes c biogenesis systems I and II and analysis of haem
      delivery pathways in Escherichia coli.
AB  - Genetic analysis has indicated that the system II pathway for c-type cytochrome
      biogenesis in Bordetella pertussis requires at least four biogenesis proteins
      (CcsB, CcsA, DsbD and CcsX). In this study, the eight genes (ccmA-H) associated
      with the system I pathway in Escherichia coli were deleted. Using B. pertussis
      cytochrome c4 as a reporter for cytochromes c assembly, it is demonstrated that a
      single fused ccsBA polypeptide can replace the function of the eight system I
      genes in E. coli. Thus, the CcsB and CcsA membrane complex of system II is likely
      to possess the haem delivery and periplasmic cytochrome c-haem ligation
      functions. Using recombinant system II and system I, both under control of IPTG,
      we have begun to study the capabilities and characteristics of each system in the
      same organism (E. coli). The ferrochelatase inhibitor N-methylprotoporphyrin was
      used to modulate haem levels in vivo and it is shown that system I can use
      endogenous haem at much lower levels than system II. Additionally, while system I
      encodes a covalently bound haem chaperone (holo-CcmE), no covalent intermediate
      has been found in system II. It is shown that this allows system I to use holo
      CcmE as a haem reservoir, a capability system II does not possess.

PMID- 16629662
TI  - Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a
      novel leucine-rich repeat protein of the human malaria parasite Plasmodium
      falciparum.
AB  - The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential
      regulator of cell division in fission and budding yeasts, where its deletion
      causes mitotic arrest. Its role in cell cycle control appears to be mediated
      through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces
      pombe. We have identified the Plasmodium falciparum Sds22 orthologue, which we
      designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We
      showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product
      interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite
      extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus
      oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M
      cell cycle checkpoint by promoting progression to germinal vesicle breakdown
      (GVBD). Confirmatory results showing the appearance of GVBD were observed when
      oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together,
      these observations suggest that PfLRR1 can regulate the cell cycle by binding to
      PP1 and regulating its activity.

PMID- 16629663
TI  - Two distinct regions of the large serine recombinase TnpX are required for DNA
      binding and biological function.
AB  - The large serine recombinase, TnpX, from the Clostridium perfringens integrative
      mobilizable element Tn4451, consists of three domains and has two known DNA
      binding regions. In this study random and site-directed mutagenesis was used to
      identify other regions of TnpX that were required for biological activity.
      Genetic and biochemical analysis of these mutants led to the identification of
      important TnpX residues in the N-terminal catalytic pocket. In addition, another
      region of TnpX (aa 243-261), which is conserved within large serine recombinases,
      was shown to be essential for both excision and insertion. Mutation of charged
      residues within this region led to a loss of biological activity and aberrant DNA
      binding. This phenotype was mediated by interaction with the distal DNA binding
      region (aa 598-707). In these mutants, removal of residues 598-707 resulted in
      loss of DNA binding, despite the presence of the primary DNA binding region (aa
      533-583). Analysis of mutations within the aa 243-261 region indicated that
      different protein conformations were involved in the insertion and the excision
      reactions. In summary, we have shown that TnpX is a complex protein that has
      multiple intra- and intermolecular interaction sites, providing insight into the
      structural and functional complexity of this important enzyme family.

PMID- 16629664
TI  - Hierarchical involvement of various GGDEF domain proteins in rdar morphotype
      development of Salmonella enterica serovar Typhimurium.
AB  - GGDEF and EAL domain proteins are involved in the turnover of the novel secondary
      messenger cyclic-di(3'-->5')-guanylic acid (c-di-GMP) in many bacteria. In this
      work the role of the 12 GGDEF domain proteins encoded by the Salmonella enterica
      serovar Typhimurium (S. Typhimurium) chromosome in rdar morphotype development
      was investigated. Previously, it was shown that the GGDEF domain protein AdrA
      activated the biosynthesis of cellulose by production of c-di-GMP. Enhancement of
      the c-di-GMP levels by overexpression of the GGDEF domain protein AdrA did lead
      to the activation of curli fimbriae biosynthesis through the elevated expression
      of CsgD and CsgA. Although knock-out of the chromosomal copy of adrA influenced
      CsgA expression, CsgD expression was not altered, although more than half of the
      total cellular c-di-GMP was produced by AdrA at 16 h of growth. On the other
      hand, chromosomally encoded GGDEF-EAL domain proteins STM2123 and STM3388 were
      required to additively activate CsgD expression on a transcriptional and post
      transcriptional level. Enhanced c-di-GMP levels did overcome temperature
      regulation of rdar morphotype expression by activation of curli fimbriae as well
      as cellulose biosynthesis through CsgD expression. Thus in the regulatory cascade
      leading to rdar morphotype expression c-di-GMP activates several subsequent steps
      in the network.

PMID- 16629665
TI  - Self-control in DNA site-specific recombination mediated by the tyrosine
      recombinase TnpI.
AB  - Tn4430 is a distinctive transposon of the Tn3 family that encodes a tyrosine
      recombinase (TnpI) to resolve replicative transposition intermediates. The
      internal resolution site of Tn4430 (IRS, 116 bp) contains two inverted repeats
      (IR1 and IR2) at the crossover core site, and two additional TnpI binding motifs
      (DR1 and DR2) adjacent to the core. Deletion analysis demonstrated that DR1 and
      DR2 are not required for recombination in vivo and in vitro. Their function is to
      provide resolution selectivity to the reaction by stimulating recombination
      between directly oriented sites on a same DNA molecule. In the absence of DR1
      and/or DR2, TnpI-mediated recombination of supercoiled DNA substrates gives a
      mixture of topologically variable products, while deletion between two wild-type
      IRSs exclusively produces two-noded catenanes. This demonstrates that TnpI
      binding to the accessory motifs DR1 and DR2 contributes to the formation of a
      specific synaptic complex in which catalytically inert recombinase subunits act
      as architectural elements to control recombination sites pairing and strand
      exchange. A model for the organization of TnpI/IRS recombination complex is
      presented.

PMID- 16629666
TI  - Flk prevents premature secretion of the anti-sigma factor FlgM into the
      periplasm.
AB  - The flk locus of Salmonella typhimurium was identified as a regulator of
      flagellar gene expression in strains defective in P- and l-ring formation. Flk
      acts as a regulator of flagellar gene expression by modulating the protein levels
      of the anti-sigma28 factor FlgM. Evidence is presented which suggests that Flk is
      a cytoplasmic-facing protein anchored to the inner membrane by a single, C
      terminal transmembrane-spanning domain (TMS). The specific amino acid sequence of
      the TMS is not essential for Flk activity, but membrane anchoring is essential.
      Membrane fractionation and visualization of protein fusions of green fluorescent
      protein derivatives to Flk suggested that the Flk protein is present in the
      membrane as punctate spots in number that are much greater than the number of
      flagellar basal structures. The turnover of the anti-sigma28 factor FlgM was
      increased in flk mutant strains. Using FlgM-beta-lactamase fusions we show the
      increased turnover of FlgM in flk null mutations is due to FlgM secretion into
      the periplasm where it is degraded. Our data suggest that Flk inhibits FlgM
      secretion by acting as a braking system for the flagellar-associated type III
      secretion system. A model is presented to explain a role for Flk in flagellar
      assembly and gene regulatory processes.

PMID- 16629667
TI  - Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two
      component response regulator.
AB  - Paired two-component regulatory systems consisting of a sensor kinase and a
      response regulator are the major means by which bacteria sense and respond to
      different stimuli. The role of essential response regulator, MtrA, in
      Mycobacterium tuberculosis proliferation is unknown. We showed that elevating the
      intracellular levels of MtrA prevented M. tuberculosis from multiplying in
      macrophages, mice lungs and spleens, but did not affect its growth in broth.
      Intracellular trafficking analysis revealed that a vast majority of MtrA
      overproducing merodiploids were associated with lysosomal associated membrane
      protein (LAMP-1) positive vacuoles, indicating that intracellular growth
      attenuation is, in part, due to an impaired ability to block phagosome-lysosome
      fusion. A merodiploid strain producing elevated levels of phosphorylation
      defective MtrA (MtrA(D53N)) was partially replicative in macrophages, but was
      attenuated in mice. Quantitative real-time PCR analyses revealed that expression
      of dnaA, an essential replication gene, was sharply upregulated during
      intramacrophage growth in the MtrA overproducer in a phosphorylation-dependent
      manner. Chromatin immunoprecipitation using anti-MtrA antibodies provided direct
      evidence that MtrA regulator binds to dnaA promoter in vivo indicating that dnaA
      promoter is a MtrA target. Simultaneous overexpression of mtrA regulator and its
      cognate mtrB kinase neither inhibited growth nor sharply increased the expression
      levels of dnaA in macrophages. We propose that proliferation of M. tuberculosis
      in vivo depends, in part, on the optimal ratio of phosphorylated to non
      phosphorylated MtrA response regulator.

PMID- 16629668
TI  - The pseudo-receiver domain of CikA regulates the cyanobacterial circadian input
      pathway.
AB  - CikA (circadian input kinase) is a component of the cyanobacterial circadian
      clock that aids in synchronizing the endogenous oscillator with the external
      environment. cikA mutants of the prokaryotic circadian model organism
      Synechococcus elongatus PCC 7942 fail to reset the phase of the circadian rhythm
      of gene expression after an environmental time cue, and also exhibit reduced
      amplitude and shortened period of circadian oscillation. CikA has histidine
      protein kinase (HPK) activity that is modulated in vitro by GAF and pseudo
      receiver (PsR) domains. Here we show that the PsR domain negatively regulates HPK
      activity in vivo and also serves as an interaction module to dock CikA at a
      specific subcellular location. Phenotypes conferred by alleles that encode CikA
      variants showed that all domains except the featureless N-terminus are required
      for CikA function. Overexpression of all alleles that encode the PsR domain,
      whether or not the HPK is functional, caused a dominant arrhythmic phenotype,
      whereas overexpressed variants that lack PsR did not. Subcellular localization of
      intact CikA identified a polar focus whereas a variant without PsR showed uniform
      distribution in the cell, consistent with a model in which PsR mediates
      interaction with other input pathway components.

PMID- 16629669
TI  - P159 is a proteolytically processed, surface adhesin of Mycoplasma hyopneumoniae:
      defined domains of P159 bind heparin and promote adherence to eukaryote cells.
AB  - Mycoplasma hyopneumoniae, the causative agent of porcine enzootic pneumonia,
      colonizes the respiratory cilia of affected swine causing significant economic
      losses to swine production worldwide. Heparin is known to inhibit adherence of M.
      hyopneumoniae to porcine respiratory epithelial cilia. M. hyopneumoniae cells
      bind heparin but the identity of the heparin-binding proteins is limited.
      Proteomic analysis of M. hyopneumoniae lysates identified 27 kDa (P27), 110 kDa
      (P110) and 52 kDa (P52) proteins representing different regions of a 159 kDa
      (P159) protein derived from mhp494. These cleavage fragments were surface located
      and present at all growth stages. Following purification of four recombinant
      proteins spanning P159 (F1P159, F2P159, F3P159 and F4P159), only F3P159 and
      F4P159 bound heparin in a dose-dependent manner (K(d) values 142.37 +/- 22.01 nM;
      75.37 +/- 7.34 nM respectively). Scanning electron microscopic studies showed M.
      hyopneumoniae bound intimately to porcine kidney epithelial-like cells (PK15
      cells) but these processes were inhibited by excess heparin and F4P159.
      Similarly, latex beads coated with F2P159 and F4P159 adhered to and entered PK15
      cells, but heparin, F2P159 and F4P159 was inhibitory. These findings indicate
      that P159 is a post-translationally cleaved, glycosaminoglycan-binding adhesin of
      M. hyopneumoniae.

PMID- 16629670
TI  - The RNA polymerase-binding protein RbpA confers basal levels of rifampicin
      resistance on Streptomyces coelicolor.
AB  - RbpA is an RNA polymerase-binding protein that occurs in the actinomycete family
      of bacteria and is regulated by the disulphide stress-response sigma factor,
      sigma(R), in Streptomyces coelicolor. Here we demonstrate that rbpA null mutants
      exhibit a slow-growth phenotype and are particularly sensitive to the
      transcription inhibitor rifampicin. Strikingly, transcription mapping experiments
      revealed that rbpA expression is induced upon exposure of S. coelicolor to
      rifampicin and that this, in part, involves an increase in the activity of
      sigma(R). In contrast, the ribosomal RNA operon promoter rrnDp3, which is
      recognized by the vegetative sigma factor sigma(HrdB), was strongly inhibited by
      rifampicin. Reconstitution of RNAP from an rbpA null mutant with purified RbpA
      revealed that RbpA stimulates transcription from rrnDp3, even in the presence of
      rifampicin. The data presented suggest that RbpA confers basal levels of
      rifampicin resistance and is a novel regulator of rRNA synthesis in S.
      coelicolor.

PMID- 16629671
TI  - Candida albicans SET1 encodes a histone 3 lysine 4 methyltransferase that
      contributes to the pathogenesis of invasive candidiasis.
AB  - Candida albicans causes diverse mucosal and systemic diseases. Although this
      versatility likely depends upon carefully co-ordinated gene expression,
      epigenetic regulation in C. albicans remains poorly characterized. Screening a
      genomic expression library, we identified C. albicans Set1p as an immunogenic
      protein with homology to a lysine histone methyltransferase of Saccharomyces
      cerevisiae. In this study, we demonstrated that total immunoglobulin, IgG and IgM
      titers against a unique Set1p N-terminal fragment were significantly higher among
      patients with disseminated candidiasis (DC) or oropharyngeal candidiasis than
      controls. Disruption of SET1 resulted in complete loss of methylation of histone
      3 at lysine residue 4, hyperfilamentous growth under embedded conditions, less
      negative cell surface charges and diminished adherence to epithelial cells,
      effects that were reversed upon gene re-insertion at a disrupted locus. During
      murine DC, the null mutant was associated with prolonged survival and lower
      tissue burdens. Taken together, our findings suggest that SET1 regulates multiple
      processes important to the pathogenesis of candidiasis. The Set1p N-terminal
      fragment does not exhibit significant homology to eukaryotic or microbial
      proteins, and might represent a novel therapeutic, preventive or diagnostic
      target.

PMID- 16629672
TI  - Relapsing fever spirochaetes produce a serine protease that provides resistance
      to oxidative stress and killing by neutrophils.
AB  - The spirochaetes that cause tick-borne relapsing fever and Lyme disease are
      closely related human pathogens, yet they differ significantly in their ecology
      and pathogenicity. Genome sequencing of two species of relapsing fever
      spirochaetes, Borrelia hermsii and Borrelia turicatae, identified a chromosomal
      open reading frame, designated bhpA, not present in the Lyme disease spirochaete
      Borrelia burgdorferi. The predicted amino acid sequence of bhpA was homologous
      with the HtrA serine proteases, which are involved with stress responses and
      virulence in other bacteria. B. hermsii produced an active serine protease that
      was recognized by BhpA antibodies and the recombinant BhpA protein-degraded beta
      casein. bhpA was transcribed in vitro at all growth temperatures and
      transcription levels were slightly elevated at higher temperatures. These results
      correlated with the synthesis of BhpA during B. hermsii infection in mice. With
      the exception of Borrelia recurrentis, the bhpA gene, protein and enzymatic
      activity were found in all relapsing fever spirochaetes, but not in Lyme disease
      or related spirochaetes. Heterologous expression of bhpA in B. burgdorferi
      increased the spirochaete's resistance to both oxidative stress and killing by
      human neutrophils. Therefore, we propose that bhpA encodes a unique and
      functional serine protease in relapsing fever spirochaetes. This periplasmic
      enzyme may prevent the accumulation of proteins damaged by the innate immune
      response and contribute to the ability of the relapsing fever spirochaetes to
      achieve high cell densities in blood.

PMID- 16629673
TI  - RNase Z in Escherichia coli plays a significant role in mRNA decay.
AB  - Genetic and biochemical analysis of RNase Z in eukaryotes, such as Arabadopsis
      thaliana, and prokaryotes like Bacillus subtilis have demonstrated that this
      endoribonuclease is essential for the maturation of tRNA precursors that do not
      contain a chromosomally encoded CCA determinant. As all Escherichia coli tRNA
      transcripts have chromosomally encoded CCA determinants, the function of its
      putative RNase Z homologue, the product of the elaC gene, is not clear. Here we
      demonstrate that the E. coli ElaC protein (RNase Z) endonucleolytically processes
      B. subtilis tRNA precursors lacking a CCA determinant both in vivo and in vitro.
      More importantly, E. coli RNase Z plays a significant role in mRNA decay, a
      previously unidentified activity for the enzyme. The purified RNase Z protein
      cleaves the rpsT mRNA at locations distinct from those obtained with RNase E. As
      expected, under physiological conditions E. coli and B. subtilis tRNA precursors
      containing a CCA determinant are not substrates. These results suggest a
      potentially important new role for the RNase Z family of proteins in RNA
      metabolism, particularly in organisms lacking RNase E.

PMID- 16629674
TI  - Transport of nucleosides across the Plasmodium falciparum parasite plasma
      membrane has characteristics of PfENT1.
AB  - Like all parasitic protozoa, the human malaria parasite Plasmodium falciparum
      lacks the enzymes required for de novo synthesis of purines and it is therefore
      reliant upon the salvage of these compounds from the external environment. P.
      falciparum equilibrative nucleoside transporter 1 (PfENT1) is a nucleoside
      transporter that has been localized to the plasma membrane of the
      intraerythrocytic form of the parasite. In this study we have characterized the
      transport of purine and pyrimidine nucleosides across the plasma membrane of
      'isolated' trophozoite-stage P. falciparum parasites and compared the transport
      characteristics of the parasite with those of PfENT1 expressed in Xenopus
      oocytes. The transport of nucleosides into the parasite: (i) was, in the case of
      adenosine, inosine and thymidine, very fast, equilibrating within a few seconds;
      (ii) was of low affinity [K(m) (adenosine) = 1.45 +/- 0.25 mM; K(m) (thymidine) =
      1.11 +/- 0.09 mM]; and (iii) showed 'cross-competition' for adenosine, inosine
      and thymidine, but not cytidine. The kinetic characteristics of nucleoside
      transport in intact parasites matched very closely those of PfENT1 expressed in
      Xenopus oocytes [K(m) (adenosine) = 1.86 +/- 0.28 mM; K(m) (thymidine) = 1.33 +/-
      0.17 mM]. Furthermore, PfENT1 transported adenosine, inosine and thymidine, with
      a cross-competition profile the same as that seen for isolated parasites. The
      data are consistent with PfENT1 serving as a major route for the uptake of
      nucleosides across the parasite plasma membrane.

PMID- 16629675
TI  - The guanosine tetraphosphate (ppGpp) alarmone, DksA and promoter affinity for RNA
      polymerase in regulation of sigma-dependent transcription.
AB  - The RNA polymerase-binding protein DksA is a cofactor required for guanosine
      tetraphosphate (ppGpp)-responsive control of transcription from sigma70
      promoters. Here we present evidence: (i) that both DksA and ppGpp are required
      for in vivo sigma54 transcription even though they do not have any major direct
      effects on sigma54 transcription in reconstituted in vitro transcription and
      sigma-factor competition assays, (ii) that previously defined mutations rendering
      the housekeeping sigma70 less effective at competing with sigma54 for limiting
      amounts of core RNA polymerase similarly suppress the requirement for DksA and
      ppGpp in vivo and (iii) that the extent to which ppGpp and DksA affect
      transcription from sigma54 promoters in vivo reflects the innate affinity of the
      promoters for sigma54-RNA polymerase holoenzyme in vitro. Based on these
      findings, we propose a passive model for ppGpp/DksA regulation of sigma54
      dependent transcription that depends on the potent negative effects of these
      regulatory molecules on transcription from powerful stringently regulated sigma70
      promoters.

PMID- 16629676
TI  - Identification of Bacillus subtilis sigma-dependent genes that provide intrinsic
      resistance to antimicrobial compounds produced by Bacilli.
AB  - Bacillus subtilis produces many antibiotics of varying structures and
      specificity. Here we identify a prominent role for sigma(W), an extracytoplasmic
      function (ECF) sigma factor, in providing intrinsic resistance to antimicrobial
      compounds produced by other Bacilli. By using a panel of B. subtilis mutants
      disrupted for each of the 30 known sigma(W)-dependent operons we identified
      resistance genes for at least three different antimicrobial compounds. The ydbST
      and fosB genes contribute to resistance to antimicrobial compound(s) produced by
      B. amyloliquefaciens FZB42, the yqeZyqfAB operon provides resistance to the
      SPbeta prophage-encoded bacteriocin sublancin, and the yknWXYZ operon and yfhL
      provide resistance to the antimicrobial peptide SdpC. YfhL encodes a paralogue of
      SdpI, a membrane protein that provides immunity to SdpC. In competition
      experiments, we identify sigma(W) as a key factor in allowing B. subtilis to
      resist antibiotic killing and encroachment by competing strains. Together with
      the previous observation that sigma(W) provides inducible resistance against the
      Streptomyces antibiotic fosfomycin, these studies support the notion that
      sigma(W) controls an antibiosis regulon important in the microbial ecology of
      soil bacteria.

PMID- 16629677
TI  - Oligonucleotide cleavage and rejoining by topoisomerase III from the
      hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and
      strand annealing-promoted DNA religation.
AB  - Topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus
      (Sso topo III) is optimally active in DNA relaxation at 75 degrees C. We report
      here that Sso topo III-catalysed DNA cleavage and religation differed
      significantly in temperature dependence: the enzyme was most active in cleaving
      ssDNA containing a cleavage site at 25-50 degrees C, but was efficient in
      rejoining the cleaved DNA strand only at higher temperatures (e.g. > or = 45
      degrees C). The failure of Sso topo III to rejoin the cleaved DNA strand
      efficiently appeared to be responsible for the inability of the enzyme to relax
      negatively supercoiled DNA at low temperature (e.g. 25 degrees C). Intriguingly,
      Sso topo III facilitated DNA annealing although it showed higher affinity for
      ssDNA than for dsDNA. Religation of the DNA strand cleaved by Sso topo III was
      drastically enhanced when the DNA was allowed to anneal to a complementary non
      cleaved oligonucleotide, presumably as a result of destabilization of the
      interaction between the enzyme and the cleaved strand through the formation of
      duplex DNA. A region in the non-cleaved strand corresponding to a sequence
      containing six bases on the 5' side and two bases on the 3' side of the cleavage
      site in the cleaved strand was crucial to the annealing-promoted religation.
      However, the annealing-promoted religation was relatively insensitive to
      mismatches in this region and the region conserved for oligonucleotide cleavage,
      except for that at the 5' end of the broken strand. These results suggest that
      Sso topo III is well suited for a role in DNA rewinding, whether it leads to
      homoduplex or heteroduplex formation.

PMID- 16629678
TI  - A family of oligopeptide transporters is required for growth of Candida albicans
      on proteins.
AB  - The human fungal pathogen Candida albicans can use proteins as the sole source of
      nitrogen for growth. The secretion of aspartic proteinases, which have been shown
      to contribute to virulence of C. albicans, allows the fungus to digest host
      proteins to produce peptides that must be taken up into the cell by specific
      transporters. To understand in more detail how C. albicans utilizes proteins as a
      nitrogen source, we undertook a comprehensive analysis of oligopeptide
      transporters encoded in the C. albicans genome. We identified eight OPT genes
      encoding putative oligopeptide transporters, almost all of which are represented
      by polymorphic alleles in strain SC5314. Expression of these genes was
      differentially induced when C. albicans was grown in YCB-BSA medium, which
      contains bovine serum albumin as the sole nitrogen source. Whereas deletion of
      single OPT genes in strain SC5314 did not affect its ability to utilize proteins
      as a nitrogen source, opt123delta triple mutants had a severe growth defect in
      YCB-BSA which was rescued by reintroduction of a single copy of OPT1, OPT2 or
      OPT3. In addition, forced expression of OPT4 or OPT5 under control of the ADH1
      promoter also restored growth of an opt123delta mutant, demonstrating that at
      least OPT1-OPT5 encode functional peptide transporters. The various oligopeptide
      transporters differ in their substrate preferences, as shown by the ability of
      strains expressing specific OPT genes to grow on peptides of defined length and
      sequence. We present evidence that in addition to the known role of oligopeptide
      transporters in the uptake of tetra- and pentapeptides these proteins can also
      transport longer peptides up to at least eight amino acids in length, ensuring an
      efficient utilization of the various peptides produced via endoproteolytic
      digestion of proteins by the secreted aspartic proteinases. As even transporters
      encoded by polymorphic alleles of a single gene exhibited differences in their
      efficiency to take up specific peptides, the oligopeptide transporters represent
      an example for how the evolution of gene families containing differentially
      expressed and functionally optimized members increases the nutritional
      versatility and, presumably, the adaptation of C. albicans to different host
      niches.

PMID- 16629680
TI  - Early N400 development and later language acquisition.
AB  - Recent developmental research on word processing has shown that mechanisms of
      lexical priming are already present in 12-month-olds whereas mechanisms of
      semantic integration indexed by the N400 mature a few months later. In a
      longitudinal setting we investigated whether the occurrence of an N400 at 19
      months is associated with the children's language skills later on. To this end
      children were retrospectively grouped according to their verbal performance in a
      language test at 30 months. Children with later age-adequate expressive language
      skills already displayed an N400 at 19 months. In contrast, children with later
      poor expressive language skills who have an enhanced risk for the development of
      specific language impairment (SLI) did not show an early N400. The results imply
      that children who have deficits in their expressive language at the age of 30
      months are already impaired in their semantic development about one year earlier.

PMID- 16629681
TI  - Loudness summation and the mismatch negativity event-related brain potential in
      humans.
AB  - Abstract Infrequently omitting a sound from a repetitive sequence elicits the
      mismatch negativity (MMN) ERP response when the stimulus onset asynchrony (SOA)
      is less than 200 ms. We contrasted two alternative explanations of omission MMN.
      (1) Each sound starts a separate temporal integration process. Omissions violate
      the constancy of the temporal structure within the integration window. (2) Sounds
      preceding an omission are perceived to be louder than those followed by a sound
      within the integration period, because omissions allow the full stimulus
      aftereffect to be included in perceived loudness. We varied the SOA between 117
      and 217 ms. For this case, the temporal structure explanation predicts that no
      MMN will be elicited, whereas the loudness summation explanation predicts that
      MMN will be elicited. MMN was elicited by tone omissions with random SOA,
      suggesting that loudness summation plays an important role in the elicitation of
      omission MMN.

PMID- 16629682
TI  - Relatedness proportion effects on masked associative priming: an ERP study.
AB  - Abstract The effect of relatedness proportion (the percentage of related words in
      a list) on associative priming was investigated in two masked priming
      experiments. In Experiment 1, subjects were randomly assigned to either a high
      (80%) or low (20%) relatedness proportion condition and performed a lexical
      decision task. Semantically related and unrelated primes were briefly flashed (50
      ms) before the targets and were preceded by a mask that prevented their overt
      identification. In Experiment 2, subjects were tested in both relatedness
      proportion conditions in a categorization task; the N400, an electrophysiological
      index of lexical and semantic priming, was measured in trials that did not
      require a button press. Behavioral and electrophysiological priming effects were
      observed in both high and low relatedness proportion conditions. The observed
      priming effects were not modulated by relatedness proportion. The results are
      discussed in terms of current theories of associative priming.

PMID- 16629683
TI  - Now you feel it--now you don't: ERP correlates of somatosensory awareness.
AB  - We investigated correlates of somatosensory awareness for supra theshold stimuli
      using event-related potentials in a masking paradigm: Conscious perception of a
      weak, but suprathreshold "target" stimulus was suppressed in a significant number
      of trials when followed by a higher-intensity "mask" stimulus. ERPs were compared
      for trials with perceived versus unperceived target stimuli. Early ERPs (P60,
      N80), generated in the contralateral S1, were found independent of stimulus
      perception. In contrast, for consciously perceived target stimuli, amplitude
      enhancements were observed for the P100 and N140. Thus, early activation of S1 is
      not sufficient to warrant conscious stimulus perception. Conscious stimulus
      processing differs significantly from unconscious processing starting around 100
      ms after stimulus presentation when the signal is processed in parietal and
      frontal cortices, brain regions crucial for stimulus access into conscious
      perception.

PMID- 16629684
TI  - Reduced baroreflex cardiac sensitivity predicts increased cognitive performance.
AB  - Abstract This study evaluated the relationship between baroreceptor reflex
      sensitivity and cognitive performance. Twenty normal subjects performed the
      Uchida-Kraepelin test, a serial arithmetic task. Baroreceptor reflex sensitivity
      during a 5-min Uchida-Kraepelin test was assessed in minute periods by spectral
      analysis using the maximum-entropy method. During the task, baroreceptor reflex
      sensitivity was significantly reduced. There was an inverse between-subjects
      association between baroreceptor reflex sensitivity and the level of performance
      (number of additions completed) both at different time periods of the Uchida
      Kraepelin test and during the whole task (r=-.51). This finding supports the
      existence of a pathway mediating mutual cardiovascular-central nervous system
      influences through the baroreceptors, establishing an essential mechanism
      facilitating adaptive reactions to stressful conditions.

PMID- 16629685
TI  - Hemodynamic profile, compensation deficit, and ambulatory blood pressure.
AB  - This study hypothesized that physiologically grounded patterns of hemodynamic
      profile and compensation deficit would be superior to traditional blood pressure
      reactivity in the prediction of daily-life blood pressure. Impedance cardiography
      derived measures and beat-to-beat blood pressure were monitored continuously in
      45 subjects during baseline and four tasks. Ambulatory blood pressure measures
      were obtained combining data from one work day and one off day. The mediating
      effects of gender and family history of hypertension were considered. Only gender
      was significantly associated with hemodynamic profile. Regression analysis
      indicated that typical reactivity measures failed to predict everyday life blood
      pressure. After controlling for gender and baseline blood pressure, hemodynamic
      patterns during specific tasks proved to be strong predictors, overcoming
      limitations of previous reactivity models in predicting real-life blood pressure.

PMID- 16629686
TI  - Cardiorespiratory fitness and laboratory stress: a meta-regression analysis.
AB  - We performed a meta-regression analysis of 73 studies that examined whether
      cardiorespiratory fitness mitigates cardiovascular responses during and after
      acute laboratory stress in humans. The cumulative evidence indicates that fitness
      is related to slightly greater reactivity, but better recovery. However, effects
      varied according to several study features and were smallest in the better
      controlled studies. Fitness did not mitigate integrated stress responses such as
      heart rate and blood pressure, which were the focus of most of the studies we
      reviewed. Nonetheless, potentially important areas, particularly hemodynamic and
      vascular responses, have been understudied. Women, racial/ethnic groups, and
      cardiovascular patients were underrepresented. Randomized controlled trials,
      including naturalistic studies of real-life responses, are needed to clarify
      whether a change in fitness alters putative stress mechanisms linked with
      cardiovascular health.

PMID- 16629687
TI  - Tracking stimulus processing in Pavlovian pupillary conditioning.
AB  - The aim of the present study was to evaluate whether the anticipatory pupillary
      dilation response is a useful indicator for the examination of complex
      differential conditioning problems like patterning. A human fear conditioning
      procedure with six groups (n=20 each) was used to examine conditioned stimulus
      (CS) processing when a compound stimulus was reinforced, but not its elements
      (positive patterning) or when the elements were reinforced, but not the compound
      (negative patterning), as well as modifications in which the compound was
      replaced by either a new compound or by a new element. We found evidence for
      conditioning within 2 s after CS onset. Group differences in differential
      conditioning indicated systematic differences in CS processing due to different
      discrimination task difficulties. This study showed that the pupil response is a
      suitable indicator for human Pavlovian conditioning with high time resolution
      within and between trials.

PMID- 16629688
TI  - P300 amplitude as an indicator of externalizing in adolescent males.
AB  - Reduced P300 amplitude is reliably found in individuals with a personal or family
      history of alcohol problems. However, alcoholism is part of a broader
      externalizing spectrum that includes other substance use and antisocial
      disorders. We hypothesized that reduced P300 is an indicator of the common factor
      that underlies disorders within this spectrum. Community males (N=969) were
      assessed at age 17 in a visual oddball task. Externalizing was defined as the
      common factor underlying symptoms of alcohol dependence, drug dependence,
      nicotine dependence, conduct disorder, and adult antisocial behavior. A robust
      association was found between reduced P300 amplitude and the externalizing
      factor, and this relation accounted for links between specific externalizing
      disorders and P300. Our findings indicate that reduced P300 amplitude is an
      indicator of the broad neurobiological vulnerability that underlies disorders
      within the externalizing spectrum.

PMID- 16629689
TI  - Effects of picture content and intensity on affective physiological response.
AB  - This study evaluated the effects of affective intensity and thematic content of
      foreground photographic stimuli on various physiological response systems. This
      was accomplished by assessing responses to pictures that varied systematically in
      these parameters. Along with overall effects of picture valence reported in
      previous work, we found effects of thematic content (i.e., specific nature of
      objects/events depicted) for all measures except heart rate. In addition, we
      found that the magnitude of startle blink, skin conductance, and corrugator
      muscle reactions increased with increasing affective intensity of pictures.
      Additionally, for these three measures, intensity effects also interacted with
      effects of picture content. These results indicate that stimulus parameters of
      intensity and thematic content exert separate-and in some cases interactive
      modulatory effects on physiological reactions to emotional pictures.

PMID- 16629690
TI  - Expressive suppression during an acoustic startle.
AB  - Previous studies have shown that inhibiting negative or positive emotion
      expressive behavior leads to increased sympathetic activation. Inhibiting facial
      behavior while in an affectively neutral state has no such physiological
      consequences. This suggests that there may be something special about inhibiting
      emotion-expressive behavior. To test the boundary conditions of the suppression
      effect, acoustic startles were delivered to 252 participants in three
      experimental groups. Participants in one group received unanticipated startles.
      Participants in the other two groups were told that after a 20-s countdown a loud
      noise would occur; participants in one of these groups were further told to
      inhibit their expressive behavior. Results indicated that startle suppression
      increased sympathetic activation. These findings extend prior work on emotion
      suppression, and suggest that inhibiting other biologically based responses also
      may be physiologically taxing.

PMID- 16629691
TI  - Varieties of attention in neutral trials: linking RT to ERPs and EEG frequencies.
AB  - It is often assumed that when a neutral cue is presented in a spatial cueing
      task, attention remains at fixation until target onset. We hypothesized that
      variance in nonspatial attention and switches of attention toward target
      locations can account for variance in reaction times of neutral trials.
      Lateralized event-related potentials (ERPs) and changes in electroencephalogram
      (EEG) frequency bands served as predictor variables in a single-trial logistic
      regression analysis to predict the direction of spatial attention in cued and
      neutral trials. The contingent negative variation (CNV) and non-lateralized
      changes in the alpha band served as markers of nonspatial attention. The
      direction of attention in cued trials was reliably predicted from single-trial
      lateralized ERP components. In neutral trials, only evidence for nonspatial
      attention was found, indicated by increases in the CNV and decreases in alpha
      preceding targets to which responses were relatively fast.

PMID- 16629692
TI  - Secular trends in socio-economic status and the implications for preterm birth.
AB  - The rate of preterm birth in the developed world has been shown to be increasing,
      in part attributable to obstetric intervention. It has been suggested that this
      may be a differential increase between socio-economic groups. We aimed to assess
      whether the preterm rate in Norway is different in socio-economic groups defined
      by maternal education, and to determine the extent to which a difference is
      attributable to a socio-economic differential in obstetrical intervention, in
      terms of caesarean section or induction of labour. We used data from the Medical
      Birth Registry of Norway from 1980 to 1998 with preterm rate as the outcome and
      maternal educational level, marital status and obstetric intervention as exposure
      variables. In multivariable analyses, adjustment was made for maternal age, year
      of birth and birth order, and secular trends were assessed according to year of
      birth. The preterm birth rate was highest in the lowest socio-economic group. An
      increase of 25.2% in the preterm rate was seen over the observation period. No
      apparent differential was seen in the increase of the crude preterm rates between
      socio-economic groups, although in multivariable analyses there was a significant
      interaction between socio-economic group and time, implying a stronger effect of
      low education towards the end of the observation period attributable to
      demographic change. In conclusion, the preterm birth rate increased over time,
      but was mainly due to an increase in obstetric interventions. No closing of the
      gap between socio-economic groups was observed.

PMID- 16629693
TI  - The relationship between the neighbourhood environment and adverse birth
      outcomes.
AB  - Intrauterine growth retardation and preterm birth are more frequent in African
      American women and women of lower socio-economic status, but the reasons for
      these disparities are not fully understood. The physical and social environments
      in which these women live may contribute to these disparities. We conducted a
      multilevel study to explore whether conditions of mothers' neighbourhood of
      residence contribute to adverse birth outcomes independent of individual-level
      determinants. We analysed data from 105 111 births in 1015 census tracts in
      Louisiana during 1997-98, merging it with data from other existing sources on
      neighbourhood socio-economic status, neighbourhood physical deterioration, and
      neighbourhood density of retail outlets selling tobacco, alcohol and foods. After
      controlling for individual-level sociodemographic factors, tract-level median
      household income was positively associated with both birthweight-for-gestational
      age and gestational age at birth. Neighbourhood physical deterioration was
      associated with these birth outcomes in ecological analyses but only
      inconsistently associated with them after controlling for individual-level
      factors. Neither gestational age nor birthweight-for-gestational-age was
      associated with the neighbourhood density of alcohol outlets, tobacco outlets,
      fast-food restaurants or grocery supermarkets. We conclude that measures of
      neighbourhood economic conditions are associated with both fetal growth and the
      length of gestation independent of individual-level factors, but that readily
      available measures of neighbourhood retail outlets are not. Additional studies
      are needed to better understand the nature of environmental influences on birth
      outcomes.

PMID- 16629694
TI  - Is conception delay a risk factor for reduced gestation or birthweight?
AB  - Previous studies have suggested an association between delays in conception and
      adverse perinatal outcomes, specifically, low birthweight and preterm birth. We
      investigated the relationship between conception delay (defined as >6 months to
      become pregnant) and three perinatal outcomes: low birthweight (LBW; <2500 g),
      preterm birth (PTB; <37 weeks), and small-for-gestational-age (SGA; <10th
      percentile weight for given gestational age) using data from the Collaborative
      Perinatal Project. The study cohort was limited to pregnancies with a known time
      to-pregnancy (n = 8465; 15%). Generalised estimating equations were used to
      estimate odds ratios (OR) and 95% confidence intervals [CI] for risk of adverse
      perinatal outcomes accounting for the clustering of pregnancy outcomes for women
      with more than one pregnancy. After adjusting for confounders, all ORs were close
      to the null (LBW, OR = 1.01; 95% CI = 0.86, 1.20), (PTB, OR = 1.10; 95% CI =
      0.95, 1.27), (SGA, OR = 1.06; 95% CI = 0.91, 1.25). Thus, we found no evidence to
      support an adverse relationship between conception delay and decrements in
      gestation or birthweight among this select sample of fertile women, even after
      varying the cut-point for defining conception delay.

PMID- 16629695
TI  - Maternal miscarriage history and risk of anencephaly.
AB  - Women with a history of reproductive loss may be at an increased risk of having
      an unfavourable outcome in subsequent pregnancies. Using data from a matched case
      control study based on the record of the Epidemiological Surveillance System of
      Neural Tube Defects, we evaluated the association between history of maternal
      reproductive loss and the risk of anencephaly in three Mexican states. Mothers of
      157 cases of anencephaly and 151 controls born during the period March 2000 to
      February 2001, were interviewed about their reproductive history and other
      additional factors, including socio-economic characteristics, prenatal care, use
      of tobacco and alcohol, presence of chronic diseases, acute illnesses and fever
      during the periconceptional period, and consumption of multivitamins and
      medicines during this period; mothers who reported no prior pregnancies were
      excluded from the analysis; 58 matched case-control pairs were used for the
      analysis. After adjusting for potential confounders, women with a history of
      miscarriage in previous pregnancies had 4.58 times more risk of having a child
      with anencephaly, than those who did not have this history; OR = 4.58, [95% CI
      1.22, 17.23]. Our results suggest that a history of previous miscarriages is a
      risk indicator for anencephaly in future gestations. This does not necessarily
      mean that the miscarriage itself is the cause, but that common mechanisms could
      be involved in the aetiology of both events. Thus, women who have had histories
      of reproductive losses, especially miscarriages, should be a priority group for
      the primary and secondary prevention of neural tube defects.

PMID- 16629696
TI  - Understanding the increased risk of neural tube defect-affected pregnancies among
      Mexico-born women in California: immigration and anthropometric factors.
AB  - Mexico-born women in the United States have an unexplained twofold increased risk
      of neural tube defect (NTD)-affected pregnancies. We examined whether immigration
      characteristics were associated with the NTD risk and whether anthropometric
      factors contributed to the increased risk among Mexico-born women. Data were
      derived from a large population-based case-control study in California. In-person
      interviews were conducted with mothers of 538 (88% of eligible) NTD-affected
      fetuses/infants and mothers of 539 (88%) randomly selected non-malformed control
      infants. The crude odds ratio (OR) for NTDs among all Mexico-born women, women
      residing <2 years in the US, and women >16 years old at immigration compared with
      non-Hispanic white women was 2.4 [95% confidence interval (CI) = 1.8, 3.3], 7.2
      [95% CI = 3.7, 14.0] and 3.0 [95% CI = 2.0, 4.4], respectively. Risk for second-
      or third-generation Mexican-Americans was similar to that of white women. The
      crude OR for all Mexico-born women was reduced from 2.4 to 2.0 [95% CI = 1.3,
      3.0] and for those residing <2 years in the US from 8.4 to 7.1 [95% CI = 3.2,
      15.3] after adjustment for maternal body mass index (BMI), height, compromised
      diet, diabetes, and other known risk factors. In term pregnancies, additional
      adjustment for pregnancy weight gain reduced the OR in all Mexico-born women and
      recent immigrants by 16% and 25%, respectively. Low pregnancy weight gain (<10
      vs. 10-14 kg) was particularly associated with increased NTD risk among Mexico
      born women (OR(ADJ) = 5.8; 95% CI = 2.1, 15.8). Findings indicate that recent
      Mexican immigrants have a sevenfold increased risk for NTDs. Maternal BMI and
      height contributed very little, and inadequate weight gain contributed modestly
      to the NTD risk disparity for Mexican immigrants.

PMID- 16629697
TI  - Risk of cancer in children with the diagnosis immaturity at birth.
AB  - Cancer risk in children born before term has been assessed in a large number of
      case-control studies but very rarely in cohort studies. We carried out a cohort
      study of 35 178 children with the diagnosis immaturity at birth in the Hospital
      Discharge Register during 1977-89. The children were followed for cancer in the
      Danish Cancer Registry until 1994 and comparisons were made with incidence rates
      for all children in Denmark. The 64 observed cases of childhood cancer in the
      cohort corresponded closely to the expected number {standardised incidence ratio
      (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site
      with an observed number that deviated significantly from the expected number was
      central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI
      1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI
      1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more
      cases than controls had been exposed to diagnostic X-rays, but the result was not
      significant. Surprisingly, for those born before term, the risk of CNS tumours
      increased with increasing gestational age in the nested case-control data. Our
      results are in line with previous evidence that children born before term are not
      at increased risk for childhood cancer in general. An explanation behind the
      excess of CNS tumours could not be identified, but the effect of diagnostic X
      rays in newborns may deserve further attention.

PMID- 16629698
TI  - The Belgrade childhood diabetes study - comparison of children with type 1
      diabetes with their siblings.
AB  - A case-control study was conducted in Belgrade (about 320,000 inhabitants 0-16
      years old) during the period 1994-97, comprising 68 diabetic children (cases) and
      68 controls chosen from the siblings of the cases. Analysis using multivariable
      logistic regression analysis indicated the following independent risk factors for
      Type 1 diabetes: higher birth order, infections during the 6 months preceding the
      onset of the disease and stressful events. Out of individual stressful and
      psychological factors, 'other' stressful events (severe accident or
      hospitalisation or death of a close friend, conflict with a teacher, death of a
      pet, failure in competition, quarrel between parents, punishment, physical
      attack, war in republics of former Yugoslavia and near drowning in the pool) and
      learning problems were independent risk factor for Type 1 diabetes. The results
      obtained in this study of siblings supports the hypothesis that environmental
      factors play a role in the development of Type 1 diabetes.

PMID- 16629699
TI  - The association of the PON1 Q192R polymorphism with complications and outcomes of
      pregnancy: findings from the British Women's Heart and Health cohort study.
AB  - It has been hypothesised that paraoxonase genes would be related to adverse
      pregnancy outcomes, via a maternal or fetal effect on placental hypoperfusion and
      thrombosis. To date only two studies have assessed this possibility. In this
      study we assessed the associations of the PON1 Q192R polymorphism with self
      report of having pregnancy-induced hypertension, gestational hyperglycaemia and a
      preterm offspring birth. The associations were assessed in 3266 white women who
      were randomly selected from 23 British towns. There was no association between
      PON1 Q192R and either self-report of pregnancy-induced hypertension or
      gestational hyperglycaemia but the prevalence of reporting having a preterm birth
      increased with each R allele: per allele odds ratio 1.20 [95% confidence interval
      (CI) 1.03, 1.41]. When our results were pooled with the one previous study of the
      association of this polymorphism with preterm birth, the pooled per allele odds
      ratio was 1.19 [95% CI 1.02, 1.39]. Our findings provide some further evidence to
      suggest that PON1 Q192R is associated with preterm birth; they invite further
      investigation of both maternal and fetal genotype for PON1 Q192R in relation to
      preterm birth.

PMID- 16629700
TI  - Statistical modelling of the seasonality of preterm delivery and intrauterine
      growth restriction in rural Gambia.
AB  - We have developed a methodology for comparing the seasonal influences on two
      outcomes, when those influences may act cumulatively or instantaneously. We have
      used this to compare the seasonal pattern of intrauterine growth retardation
      (IUGR, as reflected by weight-for-gestational-age) and preterm delivery (as
      assessed by Dubowitz scoring) among 1718 infants born in rural Gambia. Both
      outcomes were analysed as binary variables: small-for-gestational-age (SGA, <10th
      centile of reference standard) and preterm (<37 weeks) respectively. Percentages
      of preterm and SGA babies show divergent seasonal patterns that might indicate
      separate aetiologies. However, seasonal effects influencing intrauterine growth
      are likely to be cumulative over the last few months of pregnancy. By modelling
      seasonality with truncated Fourier series we were able to deconvolve the
      underlying seasonal influences on fetal growth from the pattern for SGA. This
      enabled us to use seemingly unrelated biprobit regression to compare the
      underlying seasonal pattern of intrauterine growth with that governing the
      incidence of preterm delivery. We conclude that, if the seasonal factors
      affecting intrauterine growth operate over more than the last 2 months of
      pregnancy, then the seasonal patterns of the factors causing IUGR and preterm
      delivery are indistinguishable if the factors are assumed to trigger preterm
      delivery immediately, but differ if preterm delivery is assumed to be programmed
      by factors acting at conception.

PMID- 16629701
TI  - Attitudes toward participation in a pregnancy and child cohort study.
AB  - While epidemiological studies aim for high participation rates, it is becoming
      increasingly difficult to recruit and retain participants in lengthy
      observational studies. We surveyed women who recently participated in the
      Pregnancy, Infection, and Nutrition Study during their pregnancy to learn more
      about what initially motivated them to participate in the study, their attitudes
      about the study protocol, and whether they would allow their child to participate
      in future studies. Most women were motivated by their interest in science and
      learning about their pregnancy. In general, women felt quite comfortable with
      most aspects of the study. Consent forms, telephone interviews and self
      administered questionnaires were the most acceptable components of the study, but
      even specimen collection was well tolerated by this cohort. Women were less
      comfortable with the possibility of their child participating in future research.
      This survey confirmed that once women are enrolled, they tend to be willing to
      complete most components of an intensive study, suggesting that initial efforts
      for recruitment are most important.

PMID- 16629702
TI  - Immunohistological features of visceral leishmaniasis in BALB/c mice.
AB  - It has been reported that the level of protection provided by vaccines against
      murine visceral leishmaniasis (VL) is low and that progress in research on VL may
      be due to the lack of appropriate models to study protective immunity. We have
      analysed the immunohistological features occurring in BALB/c mice after
      intravenous administration of 10(3), 10(5) and 10(6) parasites of Leishmania
      infantum. Our results show that in all cases parasite administration leads to the
      establishment of infection and to the development of quantifiable
      immunohistological features which are dependent on the inoculum size. This study
      demonstrates that differences in the parasite challenge result in changes in the
      evolution of some of the parameters associated with the degree of the infection
      in the BALB/c model: level of anti-Leishmania antibodies, up-regulation of spleen
      arginase activity, balance between IFN-gamma and IL-10, extent of lymphoid
      follicle depletion in the splenic white pulp and ineffective development of
      hepatic granulomas. Also, and depending on the initial infectious inoculum, the
      absence of parasites in the bone marrow and the number of mature and empty type
      granulomas were parameters associated with protection. We think that in this
      model a challenge of the order of 10(5) parasites should prove useful for vaccine
      studies against VL.

PMID- 16629703
TI  - Transmission-reducing immunity is inversely related to age in Plasmodium
      falciparum gametocyte carriers.
AB  - Immunity to the sexual stages of Plasmodium falciparum is induced during natural
      infections and can significantly reduce the transmission of parasites to
      mosquitoes (transmission reducing activity; TRA) but little is known about how
      these responses develop with increasing age/exposure to malaria. Routinely TRA is
      measured in the standard membrane feeding assay (SMFA). Sera were collected from
      a total of 199 gametocyte carriers (median age 4 years, quartiles 2 and 9 years)
      near Ifakara, Tanzania; 128 samples were tested in the SMFA and generated TRA
      data classified as a reduction of > 50% and > 90% of transmission. TRA of > 50%
      was highest in young children (aged 1-2) with a significant decline with age
      (chi(2) trend = 5.79, P = 0.016) and in logistic regression was associated with
      prevalence of antibodies to both Pfs230 and Pfs48/45 (OR 4.03, P = 0.011 and OR
      2.43 P = 0.059, respectively). A TRA of > 90% reduction in transmission was not
      age related but was associated with antibodies to Pfs48/45 (OR 2.36, P = 0.055).
      Our data confirm that antibodies are an important component of naturally induced
      TRA. However, whilst a similar but small proportion of individuals at all ages
      have TRA > 90%, the gradual deterioration of TRA > 50% with age suggests
      decreased antibody concentration or affinity. This may be due to decreased
      exposure to gametocytes, probably as a result of increased asexual and/or
      gametocyte specific immunity.

PMID- 16629704
TI  - Antibody responses and epitope specificities to the Taenia solium cysticercosis
      vaccines TSOL18 and TSOL45-1A.
AB  - Taenia solium is a cestode parasite that causes cysticercosis in humans and pigs.
      This study examined the antibody responses in pigs immunized with the TSOL18 and
      TSOL45-1A recombinant vaccines against T. solium cysticercosis. Immunization with
      these proteins induced specific, complement-fixing antibodies against the
      recombinant antigens that are believed to be associated with vaccine-induced
      protection against T. solium infection. Sera from immunized pigs were used to
      define the linear B-cell epitopes of TSOL18 and TSOL45-1A. Prominent reactivity
      was revealed to one linear epitope on TSOL18 and two linear epitopes on TSOL45
      1A. These, and oncosphere antigens from other taeniid cestodes, contain a protein
      sequence motif suggesting that they may show a tertiary structure similar to the
      fibronectin type III domain (FnIII). Comparison of the location of linear
      antigenic epitopes in TSOL18 and TSOL45-1A within the proposed FnIII structure to
      those within related cestode vaccine antigens reveals conservation in the
      positioning of the epitopes between oncosphere antigens from different taeniid
      species.

PMID- 16629705
TI  - Parasite density and serum cytokine levels in Plasmodium vivax malaria in Turkey.
AB  - We aimed to investigate the relationship between quantitative Plasmodium vivax
      parasitaemia and serum cytokine levels in a highly endemic region of Turkey,
      where such a relation has not been investigated before. Active screening was done
      in a total of 1316 people residing in 33 villages of Sanliurfa province, Turkey.
      The study population consisted of 79 consecutive patients with P. vivax malaria,
      and a control group included 89 healthy subjects. Thick blood smears were
      examined for malaria parasite and parasite count. Serum samples were analysed for
      IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 and IL-12 by the ELISA method. Compared
      to controls, levels of pro-inflammatory cytokines, i.e. IL-1beta, IL-6 and IL-12,
      were significantly higher in patients with parasitaemia. There was a significant
      positive correlation between serum IL-10 and IL-12 levels and the parasite burden
      (r = 0.264, P = 0.024 and r = 0.264, P = 0.024, respectively). Serum IL-8 levels
      showed a significant negative correlation with parasite burden (r =-0.356, P =
      0.002). There was a positive correlation between IL-8 levels and age, while the
      opposite was observed for IL-12. High fever was correlated with IL-6 and IL-10
      levels. Compared to controls, patients with a parasite count greater than
      5000/microL had a significantly higher IL-1beta and IL-10 levels (P < 0.05),
      while the difference was not significant for patients with a parasite count less
      than 1000/microL. Thus, we can conclude that pro-inflammatory response against P.
      vivax gains more importance during periods of increased parasite burden.

PMID- 16629706
TI  - Resistance to Schistosoma mansoni by transplantation of APO Biomphalaria
      tenagophila.
AB  - Transplantation of the haematopoietic organ from Biomphalaria tenagophila (Taim
      strain, RS, Brazil), resistant to Schistosoma mansoni, to a highly susceptible
      strain (Cabo Frio, RJ, Brazil) of the same species, showed in the recipient
      snails resistance against the trematode, when a successful transplant occurred.
      The success of transplantation could be confirmed by a typical molecular marker
      of the Taim strain in haemocytes of the recipients (350 bp detected by PCR-RFLP).
      The recipient snails which did not present the donor marker in haemocytes
      (unsuccessful transplantation) were infected with the parasite. The use of an
      atoxic modelling clay for closing the hole in the transplantation site reduced
      significantly the mortality caused by bleeding after transplantation procedures.

PMID- 16629707
TI  - Further protection studies using recombinant forms of Haemonchus contortus
      cysteine proteinases.
AB  - Significant levels of protection against Haemonchus contortus have been achieved
      in sheep by vaccination with a cysteine proteinase-enriched fraction (TSBP)
      isolated from the gut of adult parasites. Protection is associated with three
      cathepsin B-like cysteine proteinases (hmcp 1, 4 & 6). Lambs vaccinated with
      these proteinases, expressed in bacteria as glutathione S-transferase fusion
      proteins, had significantly reduced (38%) worm burdens compared to challenge
      controls although, intriguingly, egg output was unaffected. Here, a repeat trial
      with similar results is reported and protection obtained compared to that induced
      by vaccination with the predicted mature forms of hmcp1, 4 and 6 expressed in
      bacteria as non-fusion proteins. Sheep immunized with a cocktail of these non
      fusion proteins had reduced faecal egg counts of 27% (P = 0.17) and worm burdens
      of 29% (P = 0.01) compared to controls. High levels of host serum IgG were
      detected in GST-hmcp and non-fusion hmcp-immunized animals, although no
      correlation with protection could be determined. Sera from these groups bound to
      the microvillar surface of the gut of H. contortus.

PMID- 16629708
TI  - Bovine splenic NK cells synthesize IFN-gamma in response to IL-12-containing
      supernatants from Babesia bovis-exposed monocyte cultures.
AB  - The spleen is a critical effector organ functioning, in haemoparasitic diseases
      like babesiosis, to destroy the pathogen and clear the host of infected
      erythrocytes. It has an important role in both innate responses and adaptive
      immune responses. Young calves demonstrate a strong spleen-dependent innate
      response to an initial infection with Babesia bovis involving the type-1
      regulating cytokines IL-12 and IFN-gamma. However, the specific splenic cell
      types that produce IFN-gamma in response to infection and the cellular factors
      that regulate the induction have not been fully determined. Splenic NKp46(+) NK
      cells were identified and purified. They consisted of CD3(-), CD2(+/-), and
      CD8(+/-) populations. NK cells responded to exogenous IL-12 and IL-18 with the
      production of IFN-gamma. Functionally, IL-18 served as a potent co-stimulant with
      IL-12 for IFN-gamma production. Finally, innate IFN-gamma production was induced
      in splenic NK cells in the presence of supernatants from B. bovis merozoite
      exposed monocytes in an IL-12 pathway-dependent manner.

PMID- 16629710
TI  - Notice of redundant publication: Plasma levels of interleukin-18 and interleukin
      12 in Plasmodium falciparum malaria.

PMID- 16629711
TI  - Cerebral edema in diabetic ketoacidosis: an underestimated complication?

PMID- 16629712
TI  - Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis.
AB  - Symptomatic cerebral edema occurs in approximately 1% of children with diabetic
      ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is
      thought to occur more frequently. Some small studies have found narrowing of the
      cerebral ventricles indicating cerebral edema in most or all children with DKA,
      but other studies have not detected narrowing in ventricle size. In this study,
      we measured the intercaudate width of the frontal horns of the lateral ventricles
      using magnetic resonance imaging (MRI) in children with DKA during treatment and
      after recovery from the DKA episode. We determined the frequency of ventricular
      narrowing and compared clinical and biochemical data for children with and
      without ventricular narrowing. Forty-one children completed the study protocol.
      The lateral ventricles were significantly smaller during DKA treatment (mean
      width, 9.3 +/- 0.3 vs. 10.2 +/- 0.3 mm after recovery from DKA, p < 0.001).
      Children with ventricular narrowing during DKA treatment (22 children, 54%) were
      more likely to have mental status abnormalities than those without narrowing
      [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p =
      0.03]. Multiple logistic regression analysis revealed that a lower initial PCO2
      level was significantly associated with ventricular narrowing [odds ratio (OR) =
      0.88, 95% confidence interval (95% CI) = 0.78-0.99, p = 0.047). No other
      variables analyzed were associated with ventricular narrowing in the multivariate
      analysis. We conclude that narrowing of the lateral ventricles is evident in just
      over half of children being treated for DKA. Although children with ventricular
      narrowing did not exhibit neurological abnormalities sufficient for a diagnosis
      of 'symptomatic cerebral edema', mild mental status abnormalities occurred
      frequently, suggesting that clinical evidence of cerebral edema in children with
      DKA may be more common than previously reported.

PMID- 16629713
TI  - Air pollution and type 1 diabetes in children.
AB  - BACKGROUND: Over the past decade, there has been a worldwide largely unexplained
      increase in the incidence of type 1 diabetes in young children. This study
      explores the quantitative role of exposure to specific air pollutants in the
      development of type 1 diabetes in children. METHODS: A total of 402 children were
      retrospectively studied. Zip code-related, time-specific birth-to-diagnosis
      exposure to five ambient air pollutants was obtained for 102 children with type 1
      diabetes and 300 healthy children receiving care at a single hospital. Pollution
      exposure levels were created by summing up zip code-specific pollution data and
      dividing by months of exposure from birth to diagnosis. Analysis employed chi2,
      two-tailed independent sample t-test and unconditional logistic regression.
      RESULTS: Odds ratio (OR) was significantly high for cumulative exposure to
      ambient ozone (O3) and sulfate (SO4) in cases compared with controls, OR = 2.89
      [95% confidence interval (CI) = 1.80-4.62] and OR = 1.65 (CI = 1.20-2.28),
      respectively, even after adjustment for several potential confounders. Passive
      smoking was more frequent in children with diabetes (30 vs. 10%, p = 0.001).
      Attending day care and breast feeding in infancy were less frequent in children
      with diabetes (14 vs. 23%, p = 0.025; 59 vs. 78%, p = 0.001). Family history of
      diabetes, autoimmune disease and drug abuse was more frequent in cases (p <
      0.01). CONCLUSION: Cumulative exposure to ozone and sulfate in ambient air may
      predispose to the development of type 1 diabetes in children. Early infant
      formula feeding and passive smoking in the household may precipitate or
      accelerate the onset of type 1 diabetes.

PMID- 16629714
TI  - Genetic association of type 1 diabetes in an Azerbaijanian population: the HLA
      DQ, -DRB1*04, the insulin gene, and CTLA4.
AB  - BACKGROUND: Little is known on the genetic susceptibility to type 1 diabetes
      mellitus (T1DM) in the nations of the former Soviet part of south-west Asia.
      OBJECTIVE: The aim of the study was to characterize the genetic association of
      T1DM in the Azeri, the majority population of Azerbaijan. SUBJECTS AND METHODS:
      One hundred and sixty patients with childhood-onset T1DM, and 271 healthy
      unrelated controls were compared in a case-control study. All declared themselves
      as Azeri. The human leukocyte antigen (HLA)-DQB1, -DQA1 alelles, of DRB1*04
      subtypes, and of insulin gene and cytotoxic T-lymphocyte-associated protein 4
      (CTLA4) single nucleotide polymorphisms were determined using polymerase chain
      reaction (PCR) techniques, the association was tested from cross-tabulations, and
      quantified using odds ratios (OR). In the non-HLA factors, analyses were also
      stratified according to the HLA-conferred risk. RESULTS: Risk for T1DM was
      associated with presence of the HLA-DQB1*02-DQA1*05, OR = 6.6 [95% confidence
      interval (CI) 4.3-10], the HLA-DQB1*0302-DQA1*03, OR = 3.9 (95% CI 2.6-6.0), and
      an unexpectedly high risk was observed for DQB1*0304, OR = 10.9, but the very
      wide CI (CI 95% 2.4-49) prompts careful interpretation. A negative association
      with diabetes was observed for the DQB1*0602, 0503, 0301, and 0601 alleles, as
      well as the DRB1*0403 subtype. A strong protection was also associated with the
      less frequent variant of the insulin gene (OR of the phenotypic positivity was
      0.28, CI 95% 0.17-0.46), while the CTLA4 +49 A/G transition was not associated
      with T1DM. CONCLUSIONS: We bring the first report on both HLA, and non-HLA
      association of T1DM from the majority Azeri population of Azerbaijan.

PMID- 16629715
TI  - Independent effects of socioeconomic status and place of residence on the
      incidence of childhood type 1 diabetes in Western Australia.
AB  - OBJECTIVE: To analyze the incidence of type 1 diabetes in 0- to 14-year olds in
      Western Australia, from 1985 to 2002, by region and socioeconomic status.
      METHODS: Primary case ascertainment was from the prospective population-based
      Western Australian Diabetes Register, and secondary case ascertainment was from
      the Western Australian Hospital Morbidity Data System. The address at diagnosis
      was used to categorize cases into urban, rural and remote areas and into five
      socioeconomic groups using the Index of Relative Socioeconomic Disadvantage.
      Denominator data were obtained from the Australian Bureau of Statistics. Poisson
      regression was used to analyze the incidence rates by area and socioeconomic
      status. RESULTS: There were a total of 1143 cases (904 urban, 190 rural and 49
      remote). Case ascertainment was estimated to be 99.8% complete. The mean annual
      age-standardized incidence from 1985 to 2002 was 18.1 per 100,000 person years in
      urban (95% CI: 16.3-19.9), 14.3 per 100,000 in rural (95% CI: 11.4-7.3) and 8.0
      per 100,000 in remote areas (95% CI: 5.8-10.3). The incidence was significantly
      higher in urban compared with rural (rate ratio 1.27, p = 0.001) and remote (rate
      ratio 2.28, p < 0.001) areas. The incidence increased with higher socioeconomic
      status. The incidence in the highest socioeconomic group was 56% greater than the
      lowest socioeconomic group (rate ratio 1.56, p < 0.001). These differences in
      incidence by socioeconomic status and region were independent of each other.
      CONCLUSIONS: Higher socioeconomic status and residence in the urban area are
      independently associated with an increased risk of childhood type 1 diabetes in
      Western Australia.

PMID- 16629716
TI  - 'The honeymoon phase' in children with type 1 diabetes mellitus: frequency,
      duration, and influential factors.
AB  - BACKGROUND: The honeymoon period (i.e., partial remission) of type 1 diabetes
      mellitus is characterized by reduced insulin requirements while good glycemic
      control is maintained. The clinical significance is the potential possibility for
      pharmacological intervention during this period to either slow down or arrest the
      ongoing destruction of the remaining beta-cells. METHODS: A group of 103 diabetic
      children, younger than 12 yr of age, were prospectively studied to assess the
      frequency, duration, and factors that may affect partial remission. At the time
      of admission, patients were characterized by age, gender, symptom duration,
      diabetic ketoacidosis (DKA), and blood sugar level at admission. The honeymoon
      period was defined as a period with insulin requirements of less than 0.5
      U/kg/day and hemoglobin A1c (HbA1c) level of less or equal to 6%. RESULTS:
      Partial remission occurred in 71, being complete in three. The length of time
      until remission was 28.6 +/- 12.3 (mean +/- SD) days. The duration of remission
      was 7.2 +/- 4.8 months. Remission rates were higher in those patients older than
      5 yr compared with those between 3 and 5 yr of age. DKA at presentation and long
      duration of symptoms were associated with lower duration of remission (p < 0.001
      and p < 0.001, respectively). Children in whom remission occurred had
      significantly lower blood glucose levels and higher pH at presentation (p < 0.001
      and p < 0.001, respectively). CONCLUSIONS: Young age and severe disease at
      presentation are associated with decreased residual beta-cells function that is
      reflected by a lower incidence of partial remission. These observations are
      important to consider in the research regarding therapies that will have the
      potential goal to induce prolonged and/or complete remission at disease onset or
      shortly thereafter.

PMID- 16629717
TI  - Comparing three theories in predicting reproductive health behavioral intention
      in adolescent women with diabetes.
AB  - BACKGROUND: Understanding factors that affect decision-making in using
      preconception planning is important to reduce the rate of unplanned pregnancies
      and pregnancy-related complications in all women with diabetes. Previously, there
      were no studies of reproductive health-related beliefs, attitudes, or behaviors
      of adolescent women with diabetes. Constructs from social cognitive models, such
      as, the health belief model (HBM), theory of reasoned action, and social
      cognitive theory, are factors that can influence these behavioral outcomes.
      OBJECTIVE: To compare the predictive powers of these three theories in regard to
      decision-making with reproductive health behaviors in teens with diabetes and to
      identify a composite model of the strongest predictors across all three theories.
      METHOD: Data were collected from a telephone interview by same-gender research
      assistants on a sample of 87 female adolescents with type 1 diabetes (T1D) from
      four medical centers using the reproductive health attitudes and behavior (RHAB)
      questionnaire. Measures represent demographic variables, constructs of the three
      theories, and behavioral outcomes. Standard multiple regression analyses were
      used to examine the prediction of the three theories in the outcome variable
      [intention for using birth control (BC)]. RESULTS: Among the three theories
      considered, the HBM explained the highest percent of variance (24.4%) in
      intention to using BC. The best composite model consisted of perceived barriers,
      cues to action, and self-efficacy (explaining 26.1% of the variance). These three
      variables were also the strongest predictors among all constructs considered.
      CONCLUSION: In this sample of adolescent females with T1D, the strongest
      predictors from the three theories for intention to using BC appeared to be
      perceived barriers, cues to action, and self-efficacy. Intervention studies to
      decrease future unplanned pregnancies in this high-risk population could focus on
      strategies to target these factors that are amenable to change.

PMID- 16629718
TI  - Pediatric stroke associated with new onset type 1 diabetes mellitus: case reports
      and review of the literature.
AB  - Neurological deterioration in children with diabetic ketoacidosis (DKA) is
      commonly caused by cerebral edema. However, stroke should also be suspected when
      focal neurological deficits are apparent, because children with hyperglycemia and
      DKA are prone to thrombosis. We report three cases of pediatric stroke associated
      with new onset type 1 diabetes mellitus (T1DM). The first case presented with
      sinovenous thrombosis, and the other two cases presented in DKA and had a late
      diagnosis of ischemic stroke following neurological deterioration. Our recent
      experiences and review of the literature emphasize the importance of early
      diagnosis, investigation, and treatment for patients that present with new onset
      T1DM and stroke.

PMID- 16629719
TI  - Newer therapeutic options for children with diabetes mellitus: theoretical and
      practical considerations.
AB  - Recent studies in adult patients with type 1 diabetes mellitus (T1DM) and T2DM
      have examined the potential utility, benefits, and side effects of agents that
      augment insulin secretion after oral ingestion of nutrients in comparison with
      intravenous nutrient delivery, the so-called incretins. Two families of incretin
      like substances are now approved for use in adults. Glucagon-like peptide-1 (GLP
      1) or agents that bind to its receptor (exenatide, Byetta) or agents that inhibit
      its destruction [dipeptidyl peptidase-IV (DPP-IV) inhibitors, Vildagliptin]
      improve insulin secretion, delay gastric emptying, and suppress glucagon
      secretion while decreasing food intake without increasing hypoglycemia.
      Pramlintide, a synthetic amylin analog, also decreases glucagon secretion and
      delays gastric emptying, improves hemoglobin A1c (HbA1C), and facilitates weight
      reduction without causing hypoglycemia. We review the historical discovery of
      these agents, their physiology [corrected] and their current applications.
      Remarkably, only one or two studies have been reported in children. Pediatricians
      caring for children with T1DM and T2DM should become familiar with these agents
      and investigate their applicability, as they seem likely to enhance our
      therapeutic armamentarium to treat children with diabetes mellitus.

PMID- 16629720
TI  - A virological survey in migrating waders and other waterfowl in one of the most
      important resting sites of Germany.
AB  - Wild birds are considered a potential reservoir or a carrier of viral diseases
      and may therefore play a role in the epidemiology of economically important or
      zoonotic diseases. In 2001 and 2002, a survey with special emphasis on virus
      isolation in migrating waders and some other birds were conducted. In one of the
      most important inland resting sites for migratory waterfowl, tracheal and cloacal
      swabs were collected from 465 waders representing 19 different species, and 165
      other birds that were not captured on purpose. A total of 42 avian viruses were
      isolated, 34 of these were identified as paramyxoviruses (PMVs). The majority of
      isolates came from waders and wild ducks, and were characterized as PMV-1. In
      contrast, PMV-4 was found in wild ducks only, PMV-6 was mainly detected in wader
      species. Four avian influenza viruses (AIVs), belonging to H4 and H3
      haemagglutinin subtype, were isolated from wild duck species. Furthermore, four
      reo-like viruses were isolated from one particular wader species for the first
      time. The majority of virus positive birds were <1 year old and did not show any
      clinical symptoms. There was no evidence for the presence of West Nile virus in
      these birds. These results confirm that the restricted resting sites in Western
      Europe must be considered as important locations for the intra- and interspecies
      transmission of avian viruses.

PMID- 16629721
TI  - Rabies, an emerging disease in Korea.
AB  - Since the first rabies case was reported in a dog in 1907, the disease was
      enzootic up to 1975 in Korea. After a steady decrease in the number of rabies
      cases from 1976 to 1984, no case was reported for 8 years from 1985 to 1992.
      Then, a resurgence of the disease was noted in 1993, and a continuous increase of
      rabies cases was observed during the following years. This report provides
      information on rabies in South Korea during the reemerging period 1993-2003. A
      total of 364 rabies cases in five different animal species and five deaths in
      human beings as a result of rabies were reported. Cattle and dogs accounted for
      46.4% and 40.4% of total animal cases, respectively, and raccoon dogs commanded
      an overwhelming majority (44/48) of rabies cases in wildlife animal species. All
      animal and human rabies cases occurred only in two provinces, Gyeonggi and
      Gangwon; majority of them in two counties of Gyeonggi and one county of Gangwon
      province that border the demilitarized zone. From the three counties, the disease
      continued to expand to the other areas of the two provinces. The average monthly
      frequency of animal rabies cases during the 11-year period peaked in January, and
      the incidence was highest during winter. There were three major rabies outbreaks
      in animals and the number of animal rabies cases increased with time. Data
      indicate that the temporal patterns were attributable to the ethology of raccoon
      dogs in the areas of outbreak.

PMID- 16629722
TI  - Prevalence of thermophilic campylobacter infections in humans, chickens and crows
      in Morogoro, Tanzania.
AB  - Prevalence of thermophilic Campylobacter infections in humans, chickens and crows
      was determined in a cross-sectional study that was carried out in urban and rural
      areas of Morogoro region, Tanzania during the period of January 2003 to December
      2004. A total of 632 human stool samples, 536 cloacal swabs from local and
      broiler chickens and 22 intestinal contents from crows were screened for presence
      of thermophilic campylobacters using Skirrow's protocol. Representative
      Campylobacter jejuni isolates from human and chicken samples were also analysed
      by polymerase chain reaction (PCR) as a definitive identification method. The
      overall prevalence of thermophilic campylobacters was 9.3% (95% CI: 7.2-11.9),
      69.8% (95% CI: 65.7-73.6) and 72.7% (95% CI: 49.8-89.3) in humans, chickens and
      crows respectively. In humans, 59 thermophilic campylobacters were isolated of
      which 96.6% were C. jejuni and 3.4%Campylobacter coli. There was a significantly
      (P<0.001) higher prevalence in young individuals (16%) than in adults (7%). Of
      341 isolates from chickens, 91.2% were C. jejuni and 8.8% were C. coli. A
      significantly (P<0.05) higher infection rate was observed in rural local chicken
      (76%) than in broilers (60%). In crows, of 16 isolates, 93.8% were C. jejuni and
      6.2% were C. coli. Definitive identification of C. jejuni by PCR revealed
      positive results in 74.1% of 243 analysed isolates. Findings in this study
      indicate high prevalence of thermophilic campylobacters in humans, chickens and
      crows in Morogoro, and a higher infection rate of C. jejuni than that of C. coli
      in different animal species. Age of humans and location of chickens were
      identified as risk factors for thermophilic Campylobacter infections. Positive
      isolates to biochemical tests that indicated negative results on PCR indicates
      the additional value of PCR for definitive diagnosis of C. jejuni.

PMID- 16629723
TI  - In vitro and in vivo effects of lufenuron on dermatophytes isolated from cases of
      canine and feline dermatophytoses.
AB  - Lufenuron is a benzyl-urea phenol compound that inhibits chitin synthesis and is
      used as an insecticide. Its efficacy in the therapy of dermatophytosis in dogs
      and cats was evaluated in several clinical studies, with contradictory results.
      We assessed the in vitro susceptibility of dermatophytes isolated from dogs and
      cats to lufenuron, and the clinical response of skin lesions to the drug.
      Dermatophyte cultures isolated from clinical cases were exposed to lufenuron by
      three different methods: direct application and application of whole blood or
      subcutaneous tissue samples obtained from a lufenuron-treated healthy dog. No
      inhibition of dermatophyte growth was observed in any of the samples after 1 week
      of incubation. Eight dogs and six cats with skin lesions were included in the in
      vivo survey. Results indicated that six of seven skin lesions that were diagnosed
      as being caused by dermatophytes did not respond to lufenuron whereas six of
      seven skin lesions that were not caused by dermatophytes improved. We concluded
      that lufenuron, in the way it was administered in this study, had no inhibitory
      activity on dermatophytes in vitro or in vivo and its clinical use as an anti
      fungal agent is questionable. An immunomodulatory effect of the drug is, however,
      possible.

PMID- 16629724
TI  - Clinical evaluation of a peptide-ELISA based upon N-terminal B-cell epitope of
      the VapA protein for diagnosis of Rhodococcus equi pneumonia in foals.
AB  - A total of 227 field samples from naturally exposed foals aged between 3 weeks
      and 6 months were used in an evaluation of a peptide-based enzyme-linked
      immunosorbent assay (ELISA) for diagnosis of Rhodococcus equi infection. A
      biotinylated peptide derived from the virulence-associated protein A (VapA) of R.
      equi, a horse pathogen, was synthesized and designated as PN11-14. The peptide
      corresponds to the N-terminal B-cell epitope TSLNLQKDEPNGRASDTAGQ of the VapA
      protein. Based upon a serum immunoglobulin (Ig)G titre of 512 as a positive cut
      off value for the R. equi infection, the ELISA provided the overall sensitivity
      of 47.62%, specificity of 69.67% and an accuracy of 59.47% with a positive
      predictive value of 57.47% for true R. equi pneumonia. The assay was improved by
      detecting VapA-specific IgGb antibodies against N-terminal B-cell epitope of the
      VapA protein rather than IgG antibodies. The VapA-IgGb ELISA showed the overall
      sensitivity of 70.47%, specificity of 72.13% and accuracy of 71.36% with a
      positive predictive value of 68.52%. Diagnosis of R. equi disease in 6-week-old
      foals showed that the VapA-IgGb ELISA provided an increasing trend (P=0.0572) in
      sensitivity of 82.4% in comparison with the VapA-IgG ELISA which showed the
      sensitivity of 58.8%. However, differences in specificity of both tests were
      statistically insignificant (P=0.357) as analysed by the McNemar test. These
      results indicated that detection of VapA-specific IgGb antibodies may be a better
      predictor of R. equi disease in foals.

PMID- 16629725
TI  - The anti-microbial activity of electrolysed oxidizing water against
      microorganisms relevant in veterinary medicine.
AB  - Standards of the German Association of Veterinary Medicine (DVG) for the
      evaluation of chemical disinfectants were used to assess the anti-microbial
      efficacy of electrolysed oxidizing water (EOW). Enterococcus faecium,
      Mycobacterium avium subspecies avium, Proteus mirabilis, Pseudomonas aeruginosa,
      Staphylococcus aureus and Candida albicans were exposed to anode EOW (pH, 3.0+/
      0.1; oxidation-reduction potential (ORP), +1100+/-50 mV; free chlorine, 400+/-20
      mg/l Cl2) and combined EOW (7:3 anode:cathode, v/v; pH, 8.3+/-0.1; ORP, 930-950
      mV; free chlorine, 271+/-20 mg/l Cl2). In water of standardized hardness (WSH),
      all bacterial strains were completely inactivated by a 30 min exposure to maximum
      10.0% anode EOW (approximately 40.0 mg/l Cl2) or 50.0% combined EOW
      (approximately 135.5 mg/l Cl2). The sensitivity ranking order for anode EOW to
      the bacterial test strains was P. mirabilis>S. aureus>M. avium ssp. avium>E.
      faecium>P. aeruginosa. P. mirabilis and S. aureus decreased to undetectable
      levels after 5 min of exposure to 7.5% anode EOW (approximately 30.0 mg/l Cl2).
      Candida albicans was completely inactivated by a 5-min exposure to 5.0% anode
      EOW. Both, anode and combined EOW exhibited no anti-microbial activities in
      standardized nutrient broth or after addition of 20.0% bovine serum to the WSH.
      Further research is necessary to evaluate the efficacy of EOW as a disinfectant
      under operating conditions in animal production facilities.

PMID- 16629726
TI  - Echinococcus multilocularis in Austrian foxes from 1991 until 2004.
AB  - The prevalence rates of Echinococcus multilocularis in foxes (n=5600) evaluated
      in several Austrian surveys conducted between 1991 and 2004 were analysed for
      spatial and temporal differences. Data from early studies (1993-1997) in which
      the intestinal scraping technique (IST) was utilized were compared with data from
      recent (1999-2004) investigations, which made use of the shaking in a vessel
      technique (SVT), and it was assessed whether or not the infection rates of
      Austrian foxes had increased between the investigated intervals. In total, data
      from 85 districts are presented and both the retrospective and recent data are
      available from 39 of these districts. A Bayesian hierarchical model of parasite
      prevalences is presented which (i) accounts for differences in the sensitivity of
      IST and SVT, (ii) incorporates spatial auto-correlation between neighbouring
      districts, (iii) investigates the possibility of a temporal shift in the
      infection status of foxes, and (iv) quantifies uncertainty at each level of the
      model. The national average prevalence rates in the mid-1990s and at the turn of
      the millennium were 2.4% (95% confidence intervals 1.1-4.8) and 3.9% (95%
      confidence intervals 1.5-8.4) respectively. Above average prevalence rates were
      observed in the western and the northern parts of the country. Evidence is also
      presented for a temporal augmentation of the prevalence rates in some districts
      in the northern and eastern parts of the country. These findings are in
      concordance with several investigations in other European states where both newly
      emerged areas and elevated levels of transmission in existing endemic areas have
      been found. None of the districts investigated here showed significant evidence
      of a drop in prevalence.

PMID- 16629727
TI  - Determination of the maximum tolerated dose and the safety index of an
      experimental fasciolicide in cattle.
AB  - The aim of the present study was to determine the maximum tolerated dose (MTD)
      and the safety index (SI) of 5-chloro-2-methylthio-6-(1-napthyloxy)1H
      benzimidazole, called compound alpha, in cattle. In addition, to search for
      possible adverse effects after treatment, the measurement of some biochemical,
      haematological and physiological parameters were also analysed. Eighteen
      crossbred heifers were divided into six groups of three animals each. Groups 1-5
      received a single oral dose of 12, 36, 60, 120 and 180 mg/kg of body weight (bw)
      of compound alpha. Group 6 served as an untreated control. To determine the
      biochemical, haematological and enzymatic parameters, sera and blood samples were
      individually taken at 0, 4, 8, 16, 32, 128, and 720 h after treatment.
      Physiological parameters such as rectal temperature, heart rate (HR), respiration
      rate (RR) and ruminal motility were measured at the time intervals mentioned
      above. Estimation of the MTD and SI was obtained by using the formula reported by
      the Food and Drug Administration (FDA), the results showing an MTD of 180
      mg/kg/bw and an SI of 15 times the recommended clinical dose. Some statistical
      differences were observed in a few of the biochemical, haematological and
      enzymatic parameters, the adverse effects being not highly representative.
      Alterations on HR and RR were statistically different (P<0.05) only in heifers
      treated with 180 mg.

PMID- 16629728
TI  - Chronic eosinophilic dermatitis in the scrotal area associated with
      stephanofilariasis infestation of charolais bull in France.
AB  - A species of stephanofilaria is recorded as the cause of chronic eosinophilic
      dermatitis in the scrotal area of one charolais bull in France. Macroscopical and
      histopathological description of the lesion are given with a brief description of
      the parasite.

PMID- 16629729
TI  - Erosive stomatitis in a white pelican (Pelecanus onocrotalus) caused by
      Piagetiella titan (Mallophaga: Menoponidae).
AB  - Two white pelicans at the garden of a restaurant in Beysehir, a county of Konya
      province were examined for the presence of ectoparasites. Nine lice were
      collected from the oral cavity of one of them. They were identified as
      Piagetiella titan. Diffuse erosions, erosive ulcers covered by dried yellowish
      brown exudate and petechial haemorrhages were observed in oral mucosa.

PMID- 16629730
TI  - Functional brain reorganization in multiple sclerosis: evidence from fMRI
      studies.
AB  - In patients with multiple sclerosis (MS), the severity of clinical signs is not
      closely related to indices of structural brain damage provided by conventional
      magnetic resonance MR. Accordingly, patients with MS may show symptom recovery
      while progressively accumulating tissue damage. Changes in functional
      organization of the cerebral cortex have been reported in functional magnetic
      resonance (fMRI) studies that have compared the activation patterns during motor,
      visual, and cognitive tasks of patients with MS with those of healthy controls.
      fMRI studies on MS have provided the results that are difficult to compare and
      may be discrepant because of differences in the criteria used for patient
      selection, the activation paradigm, the experimental design, and the MR
      acquisition parameters. Nevertheless, they do provide a new, interesting tool
      that sheds light on how the brain changes its functional organization in response
      to MS. In patients with MS, functional brain reorganization mainly consists of an
      increase in the extent of activation of the brain areas used by healthy subjects,
      as well as the recruitment of additional brain areas. These findings have been
      interpreted as adaptive or compensatory mechanisms that allow normal performance
      despite neural damage or loss. However, brain functional activity may also change
      in response to clinical disability, though the precise role of brain functional
      changes in MS has yet to fully understand. Longitudinal studies designed to
      explore the effects of both rehabilitation and pharmacological agents on brain
      plasticity might shed light on this issue.

PMID- 16629731
TI  - Are CD MRIs compatible with good neurological practice?

PMID- 16629732
TI  - Neuroform stent-assisted coil embolization of a ruptured A1 segment anterior
      cerebral artery aneurysm.
AB  - We report a case of a 71-year-old woman who presented with a ruptured wide-necked
      proximal anterior cerebral artery (ACA) aneurysm that was successfully embolized
      using Neuroform stent-assisted coiling.

PMID- 16629733
TI  - Relationship between cerebral vasomotor reactivity and white matter lesions in
      elderly subjects without large artery occlusive disease.
AB  - BACKGROUND AND PURPOSE: The relationships between cerebral vasomotor reactivity
      (CVR) and white matter lesions (WMLs) were investigated mainly in patients with
      carotid stenosis. We aimed to study the relationship in asymptomatic elderly
      subjects without large artery occlusive disease. METHODS: A total of 33 elderly
      individuals (mean age was 76.2 years) who were free from neurological deficit or
      cognitive impairment were studied. Bilateral mean blood flow velocity was
      measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler
      (TCD) system together with intravenous administration of acetazolamide as
      vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR)
      sequence of MRI were classified into two categories: subcortical deep white
      matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The
      lesions in each category were then divided into three grades (grade 0-I, grade
      II, grade III) according to the Fazekas scale. RESULTS: CVR was inversely
      associated with the extent of SDWMH and PVH. The differences in CVR were
      statistically significant among different severity of WMLs: for SDWMH (70%+/- 10%
      in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001); for
      PVH (80%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade
      III, P < .001). CONCLUSIONS: Impaired CVR is related to the extent of WMLs in
      asymptomatic elderly individuals without large artery stenosis. The findings in
      our study suggest that dysfunction of cerebral vascular autoregulation might be
      an important factor in the development of WMLs in the asymptomatic elderly
      without large artery occlusive disease.

PMID- 16629734
TI  - Sources of variability in the detection of cerebral emboli with transcranial
      Doppler during cardiac surgery.
AB  - OBJECTIVE: The application of intensity thresholds for embolus detection with
      transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion
      of high-intensity transient signals (HITS))whose intensities are below the
      threshold. The lack of consistent threshold criteria between clinical trials may
      explain part of the discrepancy in the reported HITS counts. We investigated the
      effect of choosing different thresholds on the sensitivity and specificity of
      detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers
      independently analyzed TCD recordings from 8 patients under CPB. Doppler signals
      were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles
      according to preestablished criteria. The relative intensity of Doppler signals
      was measured by two different methods (TCD software vs manual). Receiver
      Operating Characteristic curves determined the optimal threshold for each of the
      two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190
      Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD
      software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The
      optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with
      the software method and at 7 dB with the manual method (sensitivity: 96%;
      specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal
      increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS:
      Using intensity thresholds higher than the optimal for embolus detection
      decreases HITS counts. Choosing a threshold depends on the type of method used
      for measuring the signal intensity. Uniform threshold criteria and comparative
      studies between different Doppler devices are necessary for making clinical
      trials more comparable.

PMID- 16629735
TI  - Almost perfect concordance between simultaneous transcranial Doppler and
      transesophageal echocardiography in the quantification of right-to-left shunts.
AB  - BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) and transcranial
      Doppler (TCD) are the methods of choice to study patent foramen ovale (PFO), but
      there are discrepancies between the 2 concerning PFO detection. No study has
      analyzed right-to-left shunt (RLS) quantification concordance. The 2 methods are
      carried out in different hemodynamic states, and the Valsalva maneuver (VM)
      required in each also differs. The authors compared PFO detection and concordance
      of RLS quantification classifications performing the 2 studies simultaneously.
      METHODS: The authors prospectively included consecutive stroke patients
      undergoing TEE and applied the TCD protocol of the Consensus Conference.
      Echocardiographic PFO was diagnosed when at least 3 microbubbles (MBs) were
      detected in the left atrium within 3 heartbeats after opacification of the right
      atrium. RLS quantification was (1) TCD: minimum (1-10 MBs), moderate (11-25 MBs),
      and massive (>25 MBs) and (2) TEE: small (3-10 MBs), moderate (11-30 MBs), and
      large (>30 MBs). STATISTICS: contingency tables (chi(2) and K test). Results. The
      authors studied 110 patients whose mean age was 56.7 +/- 12.1 years, and 60.9%
      were men. PFO was detected at the first VM in 30% of patients with TCD and in
      31.8% with TEE. At the second VM, both methods detected the same patients
      (32.7%). RLS was minimum (14), moderate (5), and massive (17) in TCD and small
      (13), moderate (3), and large (20) in TEE. There was an almost perfect
      concordance in RLS quantification (K = 0.928, P = .001), with only 4
      discrepancies. CONCLUSIONS: Simultaneous study with TCD and TEE showed an almost
      perfect concordance in PFO detection and RLS quantification.

PMID- 16629736
TI  - Comparison of asymmetry in cerebral blood flow between brain hemispheres using
      digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: Recently, endovascular techniques have gained significant
      therapeutic potential for both treatment and prevention of stroke. Cerebral
      angiography, which is an essential component of these procedures, has been used
      to provide morphological information regarding condition of blood vessels. In
      this study, we propose to determine the possibility of acquiring information
      regarding cerebral blood flow (CBF) in addition to morphologic information from
      data routinely available during angiography. METHODS: Digital subtraction
      angiography sequences were obtained for eight patients having occlusive disease
      in internal carotid artery (ICA) territories. Two regions-of-interest (ROIs)
      corresponding to the two brain hemispheres on AP view were delineated. For each
      image, the average pixel value within each ROI was calculated and used to
      generate time-density curves. Indices obtained from each curve were compared with
      each other and with the results obtained from the single photon emission computed
      tomography (SPECT) studies performed a pre- or postangiography procedure.
      RESULTS: Comparison between ICA stenosis and cerebral perfusion measurements
      revealed that cerebral perfusion deficit can be independent of arterial occlusive
      disease. The indices obtained from the time-density curves exhibit a correlating
      trend with the results from SPECT studies. However, lack of sufficient sample
      data prevented any meaningful statistical analysis to be conducted. CONCLUSIONS:
      We have developed a technique for utilizing the angiographic data for the
      important task of routinely and easily measuring CBF. Availability of CBF
      measurements during cerebral angiography may favorably impact upon the
      appropriate use of endovascular procedures and potentially contribute to the
      reduction of morbidity and mortality associated with stroke.

PMID- 16629737
TI  - Measurement of cortical thickness in 3D brain MRI data: validation of the
      Laplacian method.
AB  - OBJECTIVES: We aimed to determine the precision of the Laplacian approach for
      cortical thickness measurement due to changes in computational and acquisition
      parameters. We compared these results to two other methods widely used in
      clinical research using brain MRI data. MATERIALS AND METHODS: Brain MRI scans
      were obtained in 10 healthy adults using three different sets of acquisition
      parameters. The first and the second acquisitions used different slice thickness
      but the same head position. The third scan was performed after head
      repositioning. We measured cerebral cortical thickness in all brain segmentations
      using three thickness methods: Laplacian, nearest distance, and the orthogonal
      projection. RESULTS: The Laplacian method demonstrated the least variability with
      regard to the effect of interchange of boundaries, slice thickness, and
      repositioning of the head, compared with the other two methods. CONCLUSION: The
      Laplacian method is the most precise and reliable tool for in vivo cortical
      thickness measurement using brain MRI data.

PMID- 16629738
TI  - Amygdalae calcifications associated with disease duration in lipoid proteinosis.
AB  - OBJECTIVES: To describe imaging findings of central nervous system involvement in
      patients with lipoid proteinosis. METHODS: Patients with lipoid proteinosis
      followed in the dermatology and neurology departments of the State University of
      Campinas between 2002 and 2004 were evaluated using high-resolution MRI and
      computerized tomography (CT). RESULTS: We reviewed the charts of three patients
      (two women) with lipoid proteinosis with, ages ranging from 5 to 44 years.
      Symptomatic disease duration ranged from 2 to 39 years. MRI scans showed
      hypointense signal in FLAIR and T2 images in the amygdalae in two of three
      patients. Brain CT scans from two patients showed that MRI findings were
      calcifications. The calcification was more evident in patients with longer
      disease duration. Epilepsy was identified in one patient with longer disease
      duration. No other epileptogenic lesion was identified on MRI in this patient.
      CONCLUSION: Lipoid proteinosis is associated with bilateral amygdalae
      calcification. These findings were more evident in patients with longer disease
      duration. Epilepsy, when present, may be related to these calcifications.
      Patients with lipoid proteinosis should be followed with MRI/CT in order to
      identify these abnormalities.

PMID- 16629739
TI  - Lhermitte-Duclos disease: case report.
AB  - Lhermitte-Duclos disease is a rare disorder with an unknown pathogenesis. A
      single report of a pathological proven case of Lhermitte-Duclos disease is
      presented with clinical, imaging, and histopathological findings. A brief review
      of the condition is provided with an emphasis on imaging description.

PMID- 16629740
TI  - Progressive cerebral disease in lymphomatoid granulomatosis causes anterograde
      amnesia and neuropsychiatric disorder.
AB  - The authors report neuropsychological (NP) and serial quantitative magnetic
      resonance imaging (MRI) findings of a 29-year-old woman with lymphomatoid
      granulomatosis (LG). Disease course was characterized by acute psychosis, tremor,
      fever, seizures, and progressive cognitive impairment. At the time of symptom
      onset, brain MRI revealed mild lesion volume and normal parenchymal volume. This
      was followed by dramatic progression of brain lesions and atrophy over 2 years,
      at which point the patient expired. Atrophy was most prominent in the mesial
      temporal lobes. NP testing revealed marked amnesia and mild impairments in other
      cognitive domains. To our knowledge, this is the first recorded case of LG in
      which bilateral temporal lobe atrophy is evident and accompanied by anterograde
      amnesia. We speculate that temporal lobe atrophy was influenced by the
      established susceptibility of this region in various neurological diseases.

PMID- 16629741
TI  - Thickening of multiple cranial nerves in a patient with extranodal peripheral T
      cell lymphoma.
AB  - A 57-year-old male became aware of a subcutaneous tumor in March 2001.
      Histopathological examination showed peripheral T-cell lymphoma. He achieved
      complete remission after chemotherapy. Later the lymphoma relapsed in the
      subcutaneous lesion and chemotherapy was performed again. In April 2003, he
      developed diplopia, dysarthria, and dysphagia. Abnormal lymphoid cells were found
      in the cerebrospinal fluid. An immunophenotypical study disclosed that CD2, CD3,
      CD5, and CD8 were positive. Rearrangement of TCR was detected by Southern
      blotting. Cranial magnetic resonance imaging did not detect any intraparenchymal
      lesions, but thickening of multiple cranial nerves was detected. These nerves
      were homogeneously enhanced by gadolinium-DTPA. After intrathecal chemotherapy,
      atypical cells disappeared from the cerebrospinal fluid and thickening of the
      cranial nerves was resolved. Finally, lymphoma spread to the bone marrow, and the
      patient died in July 2003.

PMID- 16629742
TI  - CT and CT-perfusion findings of reversible leukoencephalopathy during triple-H
      therapy for symptomatic subarachnoid hemorrhage-related vasospasm.
AB  - BACKGROUND: Reversible leukoencephalopathy syndrome (RLS) is an acute
      neurological syndrome associated with altered mental status and visual
      disturbances described in patients with sudden elevations in systemic blood
      pressure and other medical conditions. In this process, neuroimaging studies
      usually demonstrate diffuse edema involving the subcortical structures of the
      posterior regions of the brain. Triple H (HHH) therapy is an established
      treatment for symptomatic vasospasm following subarachnoid hemorrhage (SAH). RLS
      has not been reported in the scientific literature as a complication of HHH
      therapy with perfusion computed tomography (CTP) imaging documentation. CASE: A
      73-year-old woman developed iatrogenic RLS during HHH therapy for SAH-related
      vasospasm. The computed tomography (CT) revealed bilateral parieto-occipital
      hypodensities. The CTP study showed increased cerebral blood volume and blood
      flow as well as decreased mean transit time in both parietal-occipital regions,
      which is compatible with vasogenic edema. CONCLUSION: The induction of
      hypertension as part of HHH therapy for SAH-related cerebral vasospasm may result
      in RLS. Therefore, it should be considered as a potentially reversible cause in
      the differential diagnosis of neurological deterioration in SAH patients while on
      HHH therapy. CTP study can offer an alternative for the assessment of this
      cerebrovascular syndrome.

PMID- 16629743
TI  - Unusual case of 2 renal cell carcinoma metastases ipsilateral to an occluded
      internal carotid artery.
AB  - Hemodynamic factors may play a role in the seeding and subsequent growth of
      cerebral metastasis. The authors present a case with 2 foci of cerebral
      metastasis in the same vascular territory ipsilateral to an occluded internal
      carotid artery. A 65-year-old man with chronic left frontal lobe infarct and left
      internal carotid artery occlusion was diagnosed with 2 large hemorrhagic
      metastases in the left middle cerebral artery territory. Diminished flow signals
      were seen in the trunk and branches of the left middle cerebral artery on
      magnetic resonance angiography. This case illustrates preferential seeding and
      growth of cerebral metastases in a region of the brain with diminished blood
      flow.

PMID- 16629744
TI  - Quantitation of regional cerebral blood flow: the next chapter in digital
      subtraction angiography.

PMID- 16629746
TI  - The rhizosphere: 'soil compartment influenced by the root'.

PMID- 16629747
TI  - Molecular-based strategies to exploit Pseudomonas biocontrol strains for
      environmental biotechnology applications.
AB  - Exploitation of beneficial plant-microbe interactions in the rhizosphere can
      result in the promotion of plant health and have significant implications for low
      input sustainable agriculture applications such as biocontrol. Bacteria such as
      Bacillus and Pseudomonas, and fungi such as Trichoderma, have been developed as
      commercial biocontrol products. Registration of microbial inocualants as
      biocontrol agents in either the European Union or the United States requires
      production of extensive dossiers covering efficacy, safety and risk assessment.
      Despite the fact that a number of Pseudomonas biocontrol products have been
      marketed there are still some limitations hampering the development of this
      technology for widespread use in agriculture. Although many strains show good
      performance in specific trials, this is often not translated into consistent,
      effective biocontrol in diverse field situations. Advances in 'Omics' technology
      and the publication of complete genome sequences of a number of plant-associative
      bacterial strains, has facilitated investigations into the molecular basis
      underpinning the establishment of beneficial plant-microbe interactions in the
      rhizosphere. The understanding of these molecular signalling processes and the
      functions they regulate is fundamental to promoting beneficial microbe-plant
      interactions, to overcome existing limitations and to designing improved
      strategies for the development of novel Pseudmonas biocontrol inoculant
      consortia.

PMID- 16629748
TI  - Symbiotic bacteria as a determinant of plant community structure and plant
      productivity in dune grassland.
AB  - Symbiotic interactions are thought to play a key role in ecosystems. Empirical
      evidence for the impact of symbiotic bacteria on plant communities is, however,
      extremely scarce because of experimental constraints. Here, in three
      complementary experiments, we show that nitrogen-fixing rhizobia bacteria act as
      a determinant of plant community structure and diversity. Grassland microcosms
      inoculated with a mixture of rhizobia had a higher above-ground plant
      productivity (+35%), contained more nitrogen (+85%) and had significant higher
      community evenness (+34%) than control microcosms without rhizobia. Moreover,
      three of the four studied legume species required rhizobia to successfully
      coexist with other plant species. In contrast, the growth and survival of three
      grass and five forb species were not affected by the presence or absence of
      rhizobia. Finally, our results also showed that the legume species largely relied
      on symbiotically fixed nitrogen, both in the field and in the microcosms. This
      indicates that results in the microcosms are indicative for processes occurring
      in the field. It is concluded that symbiotic interactions between plants and
      prokaryotes can contribute to plant productivity, plant community structure and
      acquisition of limiting resources in legume-rich grassland communities.

PMID- 16629749
TI  - In situ quantitation of the spatial scale of calling distances and population
      density-independent N-acylhomoserine lactone-mediated communication by
      rhizobacteria colonized on plant roots.
AB  - We used computer-assisted microscopy at single cell resolution to quantify the in
      situ spatial scale of N-acylhomoserine lactone (AHL)-mediated cell-to-cell
      communication of Pseudomonas putida colonized on tomato and wheat root surfaces.
      The results of this in situ quantification study on close-to-natural surfaces
      challenge the conventional view of a quorum group requirement of high cell
      densities for this type of bacterial communication. In situ image analysis
      indicated that the effective 'calling distance' on root surfaces was most
      frequent at 4-5 microm, extended to 37 microm in the root tip/elongation zone and
      further out to 78 microm in the root hair zone. The spatial scale of these
      calling distances is very long-range in proportion to the size of individual
      bacteria. Geostatistical modeling analysis implicated the importance of AHL
      gradients mediating effective communication between remote cells. We conclude
      that AHL-mediated cell-to-cell communication occurs not only within dense
      populations, but also in very small groups and over long ranges between
      individual bacteria, and therefore this cellular activity is more commonplace and
      effective than hitherto predicted. We propose that this cell-to-cell
      communication is governed more by the in situ spatial proximity of cells within
      AHL-gradients than the requirement for a quorum group of high population density.

PMID- 16629750
TI  - Investigations of Rhizobium biofilm formation.
AB  - The development of nitrogen-fixing nodules of the Rhizobium-legume symbiosis,
      especially the early stages of root hair deformation and curling, infection
      thread formation, and nodule initiation, has been well studied from a genetic
      standpoint. In contrast, the factors important for the colonization of surfaces
      by rhizobia, including roots-an important prerequisite for nodule formation-have
      not been as thoroughly investigated. We developed conditions for analyzing the
      ability of two fast-growing rhizobia, Sinorhizobium meliloti and Rhizobium
      leguminosarum bv. viciae, to produce biofilms on abiotic surfaces such as glass,
      plastic microtiter plates, sand and soil as a prelude to characterizing the genes
      important for aggregation and attachment. Factors involved in adherence to
      abiotic surfaces are likely to be used in rhizobial attachment to legume root
      cells. In this report, we show that S. meliloti exopolysaccharide-deficient
      mutants as well as exopolysaccharide overproducers exhibit reduced biofilm
      phenotypes that show parallels with their nodulation abilities. We also
      investigated two flagella-less S. meliloti mutants and found them to have reduced
      biofilming capabilities. To investigate whether there was a symbiotic phenotype,
      we tested one of the Fla- mutants on two different S. meliloti hosts, alfalfa and
      white sweetclover, and found that nodule formation was significantly delayed on
      the latter.

PMID- 16629751
TI  - Survival of gfp-tagged antagonistic bacteria in the rhizosphere of tomato plants
      and their effects on the indigenous bacterial community.
AB  - The survival and colonization patterns of Pseudomonas putida PRD16 and
      Enterobacter cowanii PRF116 in the rhizosphere of greenhouse-grown tomato plants
      and the effects of their inoculation on the indigenous bacterial community were
      followed by selective plating, molecular fingerprinting, and confocal laser
      scanning microscopy (CLSM) over 3 weeks. Both strains, which showed in vitro
      antagonistic activity against Ralstonia solanacearum, were previously tagged with
      gfp. Seed and root inoculation were compared. Although plate counts decreased for
      both gfp-tagged antagonists, PRD16 showed a better survival in the rhizosphere of
      tomato roots independent of the inoculation method. Analysis of 16S rRNA gene
      fragments amplified from total community DNA by denaturing gradient gel
      electrophoresis and CLSM confirmed the decrease in the relative abundance of the
      inoculant strains. Pronounced differences in the Pseudomonas community patterns
      for plants inoculated with PRD16 compared to the control were detected 3 weeks
      after root inoculation, indicating a longer-lasting effect. Analysis by CLSM
      showed rather heterogeneous colonization patterns for both inoculant strains. In
      comparison with seed inoculation, root inoculation led to a much better
      colonization as evidenced by all three methods. The colonization patterns
      observed by CLSM provide important information on the sampling strategy required
      for monitoring inoculant strains in the rhizosphere.

PMID- 16629752
TI  - Rhizosphere bacteria affected by transgenic potatoes with antibacterial
      activities compared with the effects of soil, wild-type potatoes, vegetation
      stage and pathogen exposure.
AB  - A greenhouse experiment was performed to analyze a potential effect of
      genetically modified potatoes expressing antibacterial compounds
      (attacin/cecropin, T4 lysozyme) and their nearly isogenic, nontransformed
      parental wild types on rhizosphere bacterial communities. To compare plant
      transformation-related variations with commonly accepted impacts caused by
      altered environmental conditions, potatoes were cultivated under different
      environmental conditions, for example using contrasting soil types. Further,
      plants were challenged with the blackleg pathogen Erwinia carotovora ssp.
      atroseptica. Rhizosphere soil samples were obtained at the stem elongation and
      early flowering stages. The activities of various extracellular rhizosphere
      enzymes involved in the C-, P- and N-nutrient cycles were determined as the rates
      of fluorescence of enzymatically hydrolyzed substrates containing the highly
      fluorescent compounds 4-methylumbelliferone or 7-amino-4-methyl coumarin. The
      structural diversity of the bacterial communities was assessed by 16S rRNA-based
      terminal restriction fragment length polymorphism analysis, and 16S rRNA gene
      clone libraries were established for the flowering conventional and T4 lysozyme
      expressing Desiree lines grown on the chernozem soil, each line treated with and
      without E. carotovora ssp. atroseptica. Both genetic transformation events
      induced a differentiation in the activity rates and structures of associated
      bacterial communities. In general, T4 lysozyme had a stronger effect than
      attacin/cecropin. In comparison with the other factors, the impact of the genetic
      modification was only transient and minor, or comparable to the dominant
      variations caused by soil type, plant genotype, vegetation stage and pathogen
      exposure.

PMID- 16629753
TI  - Effects of site and plant species on rhizosphere community structure as revealed
      by molecular analysis of microbial guilds.
AB  - The bacterial and fungal rhizosphere communities of strawberry (Fragaria ananassa
      Duch.) and oilseed rape (Brassica napus L.) were analysed using molecular
      fingerprints. We aimed to determine to what extent the structure of different
      microbial groups in the rhizosphere is influenced by plant species and sampling
      site. Total community DNA was extracted from bulk and rhizosphere soil taken from
      three sites in Germany in two consecutive years. Bacterial, fungal and group
      specific (Alphaproteobacteria, Betaproteobacteria and Actinobacteria) primers
      were used to PCR-amplify 16S rRNA and 18S rRNA gene fragments from community DNA
      prior to denaturing gradient gel electrophoresis (DGGE) analysis. Bacterial
      fingerprints of soil DNA revealed a high number of equally abundant faint bands,
      while rhizosphere fingerprints displayed a higher proportion of dominant bands
      and reduced richness, suggesting selection of bacterial populations in this
      environment. Plant specificity was detected in the rhizosphere by bacterial and
      group-specific DGGE profiles. Different bulk soil community fingerprints were
      revealed for each sampling site. The plant species was a determinant factor in
      shaping similar actinobacterial communities in the strawberry rhizosphere from
      different sites in both years. Higher heterogeneity of DGGE profiles within soil
      and rhizosphere replicates was observed for the fungi. Plant-specific composition
      of fungal communities in the rhizosphere could also be detected, but not in all
      cases. Cloning and sequencing of 16S rRNA gene fragments obtained from dominant
      DGGE bands detected in the bacterial profiles of the Rostock site revealed that
      Streptomyces sp. and Rhizobium sp. were among the dominant ribotypes in the
      strawberry rhizosphere, while sequences from Arthrobacter sp. corresponded to
      dominant bands from oilseed rape bacterial fingerprints.

PMID- 16629754
TI  - The rhizosphere effect on bacteria antagonistic towards the pathogenic fungus
      Verticillium differs depending on plant species and site.
AB  - Rhizobacteria with antagonistic activity towards plant pathogens play an
      essential role in root growth and plant health and are influenced by plant
      species in their abundance and composition. To determine the extent of the effect
      of the plant species and of the site on the abundance and composition of bacteria
      with antagonistic activity towards Verticillium dahliae, bacteria isolated from
      the rhizosphere of two Verticillium host plants, oilseed rape and strawberry, and
      from bulk soil were analysed at three different locations in Germany over two
      growing seasons. A total of 6732 bacterial isolates screened for in vitro
      antagonism towards Verticillium resulted in 560 active isolates, among which
      Pseudomonas (77%) and Serratia (6%) were the most dominant genera. The
      rhizosphere effect on the antagonistic bacterial community was shown by an
      enhanced proportion of antagonistic isolates, by enrichment of specific amplified
      ribosomal DNA restriction analysis types, species and genotypes, and by a reduced
      diversity in the rhizosphere in comparison to bulk soil. Such an effect was
      influenced by the plant species and by the site of its cultivation. Altogether,
      16S rRNA gene sequencing of 66 isolates resulted in the identification of 22
      different species. Antagonists of the genus Serratia were preferentially isolated
      from oilseed rape rhizosphere, with the exception of one site. For isolates of
      Pseudomonas and Serratia, plant-specific and site-specific genotypes were found.

PMID- 16629755
TI  - Colonization of barley (Hordeum vulgare) with Salmonella enterica and Listeria
      spp.
AB  - Colonization of barley plants by the food-borne pathogens Salmonella enterica
      serovar typhimurium and three Listeria spp. (L. monocytogenes, L. ivanovii, L.
      innocua) was investigated in a monoxenic system. Herbaspirillum sp. N3 was used
      as a positive control and Escherichia coli HB101 as a negative control for
      endophytic root colonization. Colonization of the plants was tested 1-4 weeks
      after inoculation by determination of CFU, specific PCR assays and fluorescence
      in situ hybridization (FISH) with fluorescently labelled oligonucleotide probes
      in combination with confocal laser scanning microscopy (CLSM). Both S. enterica
      strains were found as endophytic colonizers of barley roots and reached up to 2.3
      x 10(6) CFU per g root fresh weight after surface sterilization. The three
      Listeria strains had 10-fold fewer cell numbers after surface sterilization on
      the roots and therefore were similar to the results of nonendophytic colonizers,
      such as E. coli HB101. The FISH/CSLM approach demonstrated not only high-density
      colonization of the root hairs and the root surface by S. enterica but also a
      spreading to subjacent rhizodermis layers and the inner root cortex. By contrast,
      the inoculated Listeria spp. colonized the root hair zone but did not colonize
      other parts of the root surface. Endophytic colonization of Listeria spp. was not
      observed. Finally, a systemic spreading of S. enterica to the plant shoot (stems
      and leaves) was demonstrated using a specific PCR analysis and plate count
      technique.

PMID- 16629756
TI  - Genetic and phenotypic microdiversity of Ochrobactrum spp.
AB  - The diversity of Ochrobactrum anthropi, Ochrobactrum intermedium, Ochrobactrum
      tritici and Ochrobactrum grignonense in agricultural soil and on the wheat
      rhizoplane was investigated. O. anthropi was isolated both from soil and from the
      rhizoplane, O. intermedium and grignonense only from bulk soil, and O. tritici
      only from the wheat rhizoplane. On the genetic level, the immunotrapped isolates
      and a number of strains from culture collection mainly of clinical origin were
      compared with rep-PCR profiling using BOX primers, and a subset of these isolates
      and strains using REP primers. The isolates clustered according to their species
      affiliation. There was no correlation between rep clusters of O. anthropi
      isolates and habitat (place of isolation). The genetic diversity of Ochrobactrum
      at the species level as well as microdiversity of O. anthropi (number of BOX
      groups) was higher in soil than on the rhizoplane. Similarity values from genetic
      rep-PCR profiles correlated positively with DNA-DNA reassociation percentages.
      Isolates with >80.7% similarity in BOX profile and >86.4% in rep profile
      clustered within the same species. Similarity analysis of rep-PCR profiles is
      hence an alternative to DNA-DNA hybridization as a genomic criterion for species
      delineation within the genus Ochrobactrum. We used the substrate utilization
      system BIOLOG-GN to compare the immunotrapped isolates on the phenetic level. For
      the isolates from bulk soil, substrate utilization versatility (number of
      utilized substrates) and substrate utilization capacity (mean conversion rate of
      substrates) were slightly but significantly higher than for the isolates from the
      rhizoplane. This trend was also seen using API 20E and 20NE systems. Plate counts
      of total bacteria and the number of immunotrapped Ochrobactrum isolates per gram
      dry weight were higher for the rhizoplane than for the soil samples. The results
      of genetic and phenotypic analyses indicated a 'rhizosphere effect'; the
      diversity and metabolic capacity of Ochrobactrum isolates were higher in bulk
      soil, and the population density was higher on the wheat rhizoplane.

PMID- 16629757
TI  - Decreased abundance and diversity of culturable Pseudomonas spp. populations with
      increasing copper exposure in the sugar beet rhizosphere.
AB  - Recent studies have indicated that culturable bacteria constitute highly
      sensitive bioindicators of metal-induced stress in soil. We report the impact of
      different copper exposure levels characteristic of contaminated agricultural
      soils on culturable Pseudomonas spp. in the rhizosphere of sugar beet. We
      observed that the abundance of Pseudomonas spp. was much more severely affected
      than that of the general population of culturable heterotrophic bacteria by
      copper. For diversity assessment, Pseudomonas isolates were divided into
      operational taxonomic units based on amplified ribosomal DNA restriction analysis
      and genomic PCR fingerprinting by universally primed PCR. Copper significantly
      decreased the diversity of Pseudomonas spp. in the rhizosphere and significantly
      increased the frequency of copper-resistant isolates. Concomitant chemical and
      biological analysis of copper in the rhizosphere and in bulk soil extracts
      indicated no rhizosphere effect and a relatively low copper bioavailability in
      the studied soil, suggesting that the observed effects of copper may occur at
      lower total concentrations in other soils. We conclude that culturable
      Pseudomonas sensu stricto constitutes a highly sensitive and relevant
      bioindicator group for the impact of copper in the rhizosphere habitat, and
      suggest that continued application of copper to agricultural soils poses a
      significant risk to successful rhizosphere colonization by Pseudomonas spp.

PMID- 16629758
TI  - Litter-forager termite mounds enhance the ectomycorrhizal symbiosis between
      Acacia holosericea A. Cunn. Ex G. Don and Scleroderma dictyosporum isolates.
AB  - The hypothesis of the present study was that the termite mounds of Macrotermes
      subhyalinus (MS) (a litter-forager termite) were inhabited by a specific
      microflora that could enhance with the ectomycorrhizal fungal development. We
      tested the effect of this feeding group mound material on (i) the
      ectomycorrhization symbiosis between Acacia holosericea (an Australian Acacia
      introduced in the sahelian areas) and two ectomycorrhizal fungal isolates of
      Scleroderma dictyosporum (IR408 and IR412) in greenhouse conditions, (ii) the
      functional diversity of soil microflora and (iii) the diversity of fluorescent
      pseudomonads. The results showed that the termite mound amendment significantly
      increased the ectomycorrhizal expansion. MS mound amendment and ectomycorrhizal
      inoculation induced strong modifications of the soil functional microbial
      diversity by promoting the multiplication of carboxylic acid catabolizing
      microorganisms. The phylogenetic analysis showed that fluorescent pseudomonads
      mostly belong to the Pseudomonads monteillii species. One of these, P. monteillii
      isolate KR9, increased the ectomycorrhizal development between S. dictyosporum
      IR412 and A. holosericea. The occurrence of MS termite mounds could be involved
      in the expansion of ectomycorrhizal symbiosis and could be implicated in nutrient
      flow and local diversity.

PMID- 16629759
TI  - Agrobacterium strains isolated from root nodules of common bean specifically
      reduce nodulation by Rhizobium gallicum.
AB  - In a previous work, we showed that non-nodulating agrobacteria strains were able
      to colonize root nodules of common bean. Both rhizobia and agrobacteria co
      existed in the infected nodules. No impact on symbiosis was found in laboratory
      conditions when using sterile gravel as a support for growth. In this study, soil
      samples originating from different geographic and agronomic regions in Tunisia
      were inoculated with a mixture of agrobacteria strains isolated previously from
      root nodules of common bean. A significant effect on nodulation and vegetal
      growth of common bean was observed. Characterization of nodulating rhizobia and
      comparison with non-inoculated controls showed a biased genetic structure. It
      seemed that Rhizobium gallicum was highly inhibited, whereas nodulation by
      Sinorhizobium medicae was favored. Co-inoculation of non-sterile soils with R.
      gallicum and agrobacteria confirmed these findings. In vitro antibiosis assays
      indicated that agrobacteria exercised a significant antagonism against R.
      gallicum.

PMID- 16629760
TI  - Sheep-urine-induced changes in soil microbial community structure.
AB  - Soil microbial communities play an important role in nutrient cycling and
      nutrient availability, especially in unimproved soils. In grazed pastures, sheep
      urine causes local changes in nutrient concentration which may be a source of
      heterogeneity in microbial community structure. In the present study, we
      investigated the effects of synthetic urine on soil microbial community
      structure, using physiological (community level physiological profiling, CLPP),
      biochemical (phospholipid fatty acid analysis, PLFA) and molecular (denaturing
      gradient gel electrophoresis, DGGE) fingerprinting methods. PLFA data suggested
      that synthetic urine treatment had no significant effect on total microbial
      (total PLFA), total bacterial or fungal biomass; however, significant changes in
      microbial community structure were observed with both PLFA and DGGE data. PLFA
      data suggested that synthetic urine induced a shift towards communities with
      higher concentrations of branched fatty acids. DGGE banding patterns derived from
      control and treated soils differed, due to a higher proportion of DNA sequences
      migrating only to the upper regions of the gel in synthetic urine-treated
      samples. The shifts in community structure measured by PLFA and DGGE were
      significantly correlated with one another, suggesting that both datasets
      reflected the same changes in microbial communities. Synthetic urine treatment
      preferentially stimulated the use of rhizosphere-C in sole-carbon-source
      utilisation profiles. The changes caused by synthetic urine addition accounted
      for only 10-15% of the total variability in community structure, suggesting that
      overall microbial community structure was reasonably stable and that changes were
      confined to a small proportion of the communities.

PMID- 16629761
TI  - An overview of fungal community diversity in diseased hop plantations.
AB  - Samples were taken from several hop fields presenting various symptoms. Fifty
      nine pure filamentous fungal strains were isolated and identified through genomic
      DNA preparations, PCR amplification of the ribosomal DNA internal transcribed
      spacer region and database interrogations. The most frequent genera were
      Alternaria (16 isolates) and Epicoccum (14 isolates). The ecosystem was shown to
      be very diverse, since as many as 27 species belonging to 17 genera were
      recovered. Furthermore, many of the isolated fungi are known to be involved in
      phytopathogenesis.

PMID- 16629762
TI  - Comparison of Betaferon, Avonex, and Rebif in treatment of relapsing-remitting
      multiple sclerosis.
AB  - OBJECTIVES: To compare the relative efficacies of Betaferon, Avonex, and Rebif in
      the treatment of relapsing-remitting multiple sclerosis (RRMS). METHODS: Ninety
      patients with RRMS were randomly allocated to the three treatment groups. The
      first group received Betaferon, the second group received Avonex, and the third
      group received Rebif for 24 months. Response to treatment was assessed at 6, 12,
      and 24 months after start of therapy. RESULTS: Of the 30 patients treated with
      Betaferon, the mean (standard deviation, SD) of relapse rate decreased from 2.2
      (0.7) to 0.7 (0.7) episodes. Correspondingly, in the 30 patients treated with
      Avonex, the mean (SD) of relapse rate decreased from 2.0 (1.2) to 1.2 (0.9) (P <
      0.001). In the 30 patients treated with Rebif, the mean (SD) of relapse rate
      decreased from 2.4 (1.0) to 0.6 (0.9) (P < 0. 01). After 2 years, 43.3% of
      patients receiving Betaferon and 56.7% of patients receiving Rebif remained
      relapse-free compared with 20% of those given Avonex. Expanded Disability Status
      Scale (EDSS) decreased by 0.7 U in Betaferon-treated patients (P < 0.001), 0.3 U
      in Rebif-treated patients (P < 0.05), and remained stable in Avonex patients.
      CONCLUSION: Treatment with Betaferon, Avenox, and Rebif significantly reduce
      relapse rate and EDSS score in patients with RRMS.

PMID- 16629763
TI  - Orthostatic heart rate variability analysis in idiopathic Parkinson's disease.
AB  - OBJECTIVES: We evaluated time and spectral analyses of 24-h heart rate
      variability (HRV) and the heart rate responses to passive tilt in patients with
      idiopathic Parkinson's disease (IPD) in order to investigate cardiovascular
      autonomic functions. MATERIAL AND METHODS: Twenty-three subjects with IPD without
      autonomic symptoms and 15 age-matched healthy controls were enrolled. Frequency-
      and time-domain HRV parameters were studied during resting and passive head-up
      tilt (HUT) test. RESULTS: All time-domain parameters were found to be low in
      patients with IPD. In patients with IPD, both low frequency (LF) and high
      frequency (HF) decreased during HUT period and no significant change in LF to HF
      ratio was noted. Both time- and frequency-domain HRV indices showed no
      correlation with age, disease severity and duration, and with l-dopa medication.
      CONCLUSION: The results indicate that impairment of autonomic nervous system
      function in IPD without autonomic symptoms is frequent, and does not show clear
      association with clinical stage and the age of the patients.

PMID- 16629764
TI  - Effect of ropinirole on visuo-motor test in newly diagnosed Parkinson's disease
      patients.
AB  - OBJECTIVES: The aim of this study was to assess the sensitivity of the visuo
      motor test (VMT) compared with the Unified Parkinson's Disease Rating Scale
      (UPDRS) in newly diagnosed Parkinson's disease (PD) patients. METHODS: VMT and
      UPDRS were carried out in 20 patients before treatment onset, 2 weeks after
      treatment with ropinirole 1.5 mg/day and 2 weeks following increasing the dose of
      ropinirole to 3.0 mg/day. RESULTS: Improvement in clinical status was seen in all
      patients, with a mean UPDRS reduction of 16.6% following treatment with
      ropinirole 1.5 mg/day, and 38.9% reduction in UPDRS observed with ropinirole 3.0
      mg/day. Initial improvement was not correlated with severity of PD, although
      further improvement with ropinirole 3.0 mg/day correlated linearly with patient's
      baseline UPDRS. Improvement in the ability to control the direction of the moving
      hand during tracing is expressed by the reduction of VMT variables following
      treatment. Mean VMT variables were 36.2% at baseline, 34.0% with ropinirole 1.5
      mg/day and 31.7% with ropinirole 3.0 mg/day. Although changes in VMT variables
      were less uniform across patients, on average, it did correlate with patients
      UPDRS. CONCLUSIONS: We suggest that VMT can be useful in the assessment of
      treatment effect on high-level motor planning and cognitive capabilities in newly
      diagnosed PD patients, added to the UPDRS which does not appropriately comply
      with those skills.

PMID- 16629765
TI  - Predictors of good prognosis in total anterior circulation infarction within 6 h
      after onset under conventional therapy.
AB  - OBJECTIVE: We investigated the predictors of good prognosis in total anterior
      circulation infarction (TACI), under conventional therapy. METHODS: We enrolled
      166 patients with first-ever ischemic stroke within 6 h after onset with symptoms
      of TACI. Sixty-three patients (38.0%) with good outcome [G group, the modified
      Rankin Disability Scale (mRS) after 3 months < or =3] and 103 patients (62.0%)
      with bad outcome (B group, mRS >3) were compared. RESULTS: On univariate
      analysis, G group patients were significantly younger, had lower score in the
      National Institutes of Health Stroke Scale (NIHSS) of total and consciousness sub
      score, had lower rate of clinical deterioration. On cranial CT at entry, three
      early CT signs [hyperdense middle cerebral artery (MCA) sign, hypodensity of >1/3
      MCA and brain swelling] were significantly more frequent in the B group. On the
      second CT at 24-48 h, infarct area as assessed by the Alberta Stroke Programme
      Early CT Score (ASPECTS) was significantly smaller in the G group. Multivariate
      analysis with logistic regression revealed age <7 0 years, NIHSS < or =15, no
      clinical deterioration, and only no brain swelling in early CT signs, and ASPECTS
      > or =7 as independent predictors of good prognosis. CONCLUSIONS: Some clinical
      variables are useful in predicting outcome in TACI within the early period after
      stroke onset.

PMID- 16629766
TI  - Acute stroke in relation to homocysteine and methylenetetrahydrofolate reductase
      gene polymorphisms.
AB  - AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause
      hyperhomocysteinemia and homocystinuria. These may be important risk factors for
      cardio and cerebrovascular diseases. We investigated whether the MTHFR C677T and
      A1298C polymorphisms contribute to hyperhomocysteinemia and increase the risk
      factor for stroke. METHODS: A total of 203 acute stroke patients and 55 controls
      were recruited. Polymorphisms were determined by using polymerase chain reaction
      restriction fragment length polymorphism (RFLP) and plasma total homocysteine
      levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS AND
      CONCLUSIONS: There were no significant differences between C677T and A1298C
      genotypes and allele frequencies in the stroke patients and controls. Total
      plasma homocysteine level was higher in the 677TT and 1298AA genotypes in stroke
      patients and especially small-vessel disease patient subgroup. Age, number of
      males, systolic-diastolic blood pressures, creatinine, vitamin B(12) and
      homocysteine levels were significantly high among stroke patients. Age, sex,
      systolic blood pressure and HDL-C were determined as risk factors for
      homocysteine levels. We also determined that the effect of A1298C polymorphism on
      homocysteine was not as high as that of C677T polymorphism in acute stroke
      patients. We conclude that the MTHFR genotype may be a modest risk factor for
      stroke in Turkish population.

PMID- 16629767
TI  - Serum Fas and Bcl-2 in patients with epilepsy.
AB  - OBJECTIVES: The present study aimed to investigate the levels of the biochemical
      markers of apoptosis (soluble Fas and Bcl-2) in the sera of children and
      adolescents with idiopathic epilepsy. MATERIALS AND METHODS: The study included
      30 children and adolescents (mean age 8.03 +/- 4.49 years) with idiopathic
      epilepsy, 16 of them were newly diagnosed, and 15 clinically healthy control
      subjects. Of the included patients, 22 had focal seizures and eight had
      generalized seizures. In addition to laboratory and radiological investigations
      needed for diagnosis and follow-up, soluble Fas (s.Fas) and Bcl-2 were assayed in
      sera of patients and controls by enzyme-linked immunosorbent assay technique.
      RESULTS: Serum levels of s.Fas and Bcl-2 were significantly higher in the
      patients group than in the control group; however, their levels were comparable
      in patients with different seizure types. Levels of s.Fas correlated positively
      with seizure severity and negatively with the duration from the last attack. Bcl
      2 levels were positively correlated to each of the duration of epilepsy, the
      severity of seizures and its frequency. There was a significant positive
      correlation between serum levels of s.Fas and that of Bcl-2 and both were
      significantly increased in patients with uncontrolled epilepsy. CONCLUSION: The
      present data demonstrate that markers of apoptosis, both the proapoptotic Fas and
      the anti-apoptotic Bcl-2, were proportionately elevated in sera of patients with
      idiopathic epilepsy, and their levels were related to the seizure severity and
      frequency.

PMID- 16629768
TI  - Increased frequency of rapid acetylator genotypes in patients with brain
      astrocytoma and meningioma.
AB  - OBJECTIVES: The arylamine N-acetyltransferase (NAT2) is a polymorphic enzyme
      involved in deactivation and activation of carcinogens through N- and O
      acetylation. We investigated the association between the genetic NAT2
      polymorphism and brain tumors by analysis of genomic DNA from 71 brain tumor
      patients and 258 healthy controls. MATERIALS AND METHODS: Seven single nucleotide
      polymorphisms of the NAT2 gene were studied by using allele-specific polymerase
      chain reaction amplification. RESULTS: Ten different NAT2 allelic variants were
      identified in both patient and control groups. A higher number of individuals
      carrying functional NAT2 genes, and therefore with a rapid acetylation phenotype,
      was found in brain tumor patients vs healthy volunteers (OR 1.79, 95% CI 1.05
      3.05; P < 0.05). This is observed either for patients suffering from meningioma
      or astrocytoma, and this is due to an increase of the wild-type NAT2*4 allelic
      variant frequency (OR 1.48, 95% CI 0.99-2.19), and a reduction of the commonest
      defective allelic variant NAT2*5B in the brain tumor patients, compared with
      healthy subjects (OR 0.54, 95% CI 0.37-0.80). CONCLUSIONS: This observation
      indicates that NAT2 could be considered as a low-penetrance gene for brain
      tumors, and that individuals carrying rapid acetylation alleles are at increased
      risk of developing brain tumors.

PMID- 16629769
TI  - Elevation of ST2 protein levels in cerebrospinal fluid following subarachnoid
      hemorrhage.
AB  - OBJECTIVE: To study the mode of appearance of ST2 in cerebrospinal fluid (CSF)
      after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Immunoprecipitation
      and subsequent immunoblotting were performed to reveal the existence of ST2 in
      CSF after SAH. CSF samples from 21 patients were analyzed for ST2 using an enzyme
      linked immunosorbent assay system. The ST2 levels were compared between serum and
      CSF after SAH. The ST2 levels in CSF were measured in six patients operated with
      other than SAH. RESULTS: ST2 was secreted into CSF after SAH. The concentration
      of ST2 was the highest in the samples of the first post-operative day and
      declined thereafter. The patients operated with other than SAH did not show the
      elevation of ST2 in CSF. CONCLUSIONS: This study revealed the presence of ST2 in
      CSF for the first time and suggested a possibility that ST2 is related to the
      inflammatory reaction in the central nervous system after SAH.

PMID- 16629770
TI  - Alteration in the copy number of mitochondrial DNA in leukocytes of patients with
      mitochondrial encephalomyopathies.
AB  - OBJECTIVES: We investigated whether mutation of mitochondrial DNA (mtDNA) affects
      the copy number of the mitochondrial genome in patients with mitochondrial
      myopathy encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and
      those with myoclonic epilepsy with ragged-red fiber (MERRF) syndromes. MATERIALS
      AND METHODS: Forty-eight Taiwanese patients with MELAS syndrome and 20 patients
      with MERRF syndrome were recruited in this study. RESULTS: In relation to
      controls, the copy numbers of mtDNA in leukocytes of patients with MELAS or MERRF
      syndrome were significantly higher at a young age but lower at an advanced age.
      In addition, MELAS patients harboring higher proportions of mtDNA with A3243G
      transition had lower mtDNA copy numbers. The MELAS or MERRF patients with multi
      system disorders had lower mtDNA copy numbers in leukocytes. Furthermore, higher
      proportions of mtDNA with 4977 bp deletion were found in leukocytes of MERRF
      patients with multi-system involvement. CONCLUSION: In leukocytes, alteration in
      the copy number of mtDNA is related to the proportion of mtDNA with a point
      mutation or large-scale deletion, which may serve as a biomarker in the
      pathogenesis and disease progression of MELAS and MERRF syndromes.

PMID- 16629771
TI  - Novel mutations at carboxyl terminus of CIC-1 channel in myotonia congenita.
AB  - OBJECTIVES: Myotonia congenita (MC), caused by mutations in the muscle chloride
      channel (CLCN1) gene, can be inherited dominantly or recessively. The mutations
      at the carboxyl terminus of the CLCN1 gene have been identified in MC patients,
      but the functional implication of these mutations is unknown. MATERIAL AND
      METHODS: Direct sequencing of polymerase chain reaction products covering the
      whole coding region of the CLCN1 gene was performed in a MC family. This study
      was designed to investigate the clinical manifestations and genetic analysis of
      the CLCN1 gene. RESULTS: We identified two novel mutations, 2330delG and 1892C>T,
      from a genetic screening of the CLCN1 gene in the MC family. The 2330delG mutant
      allele producing a fs793X truncated protein was identified in a heterozygous
      state in all the patients. The 1892C>T nucleotide change induced a missense
      mutation (T631I) found in several asymptomatic individuals, indicating that it
      may not be associated with MC. Intriguingly, the 2330delG mutation was also found
      in an asymptomatic subject who also carried the 1892C>T mutation. CONCLUSION: The
      data indicate that the fs793X mutant protein causes dominantly inherited MC.
      Because the mutation has been found in a recessive pedigree, the fs793X mutation
      may have a dual inheritance pattern.

PMID- 16629772
TI  - Gender change and its impact on the course of multiple sclerosis.
AB  - We report the case of a 22-years old genotypic women suffering from a relapsing
      remitting multiple sclerosis (MS) according to the Poser criteria. In this
      patient, a gender change had been performed by androgen-supplementation and
      surgical intervention. During gender change, the patient experienced further
      relapses. Different immunomodulatory and immunosuppressive treatment strategies
      did not stabilise the course of MS in this patient. Actually, an escalating
      therapy with mitoxantrone has been initiated. During the observation period the
      patient received long-term testosterone-supplementation. Testosterone levels were
      elevated in the serum of this genotypic female MS patient under such a hormonal
      treatment compared to normal ranges before. The clinical course of the patient is
      presented in this case. As there are several studies investigating an
      immunomodulatory impact of hormones on the course of MS or experimental allergic
      encephalomyelitis, we discuss the presented case and a possible influence of
      androgens in this patient.

PMID- 16629773
TI  - Exploring the relationship between Parkinson's disease and hemifacial spasm.
AB  - Case reports of co-existent Parkinson's disease (PD) and hemifacial spasm (HFS)
      suggest that there may be a relationship between these conditions. Three of 300
      (1%) PD patients presented with HFS compared with 0/300 (0%) controls. The mean
      age of the three PD patients with HFS was 68.7 +/- 8.0 (60-76) years, with the
      majority having left-sided HFS. All three patients developed HFS symptoms at
      around the onset of PD and they were significantly older than the 100 patients
      with HFS alone (P < 0.05). Our study demonstrated no significant increased risk
      of HFS amongst the general PD population and hence HFS symptoms are unlikely to
      be of clinical importance for most PD patients.

PMID- 16629774
TI  - Is ischemic cerebrovascular disease a risk factor for dementia in patients with
      Parkinson's disease?

PMID- 16629775
TI  - Cabergoline in Huntington's disease: the first case report.

PMID- 16629777
TI  - Asthma, a priority for the allergist.

PMID- 16629778
TI  - Local oropharyngeal side effects of inhaled corticosteroids in patients with
      asthma.
AB  - The widespread use of inhaled corticosteroids (ICS) for the treatment of
      persistent asthma, although highly effective, may be associated with both
      systemic and local side effects. Systemic side effects of ICS have been
      extensively studied. In contrast, relatively few studies have been performed to
      specifically evaluate local side effects of ICS. These local side effects-
      including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough--are
      generally viewed as minor complications of therapy. However, they can be
      clinically significant, affect patient quality of life, hinder compliance with
      therapy, and mask symptoms of more serious disease. Local side effects result
      from deposition of an active ICS in the oropharynx during administration of the
      drug. Numerous factors can influence the proportion of an inhaled dose that is
      deposited in the oropharyngeal cavity, including the ICS formulation, type of
      delivery system, and patient compliance with administration instructions.
      Therefore, the incidence of local side effects can vary widely. The goal in
      developing a new ICS is to include key pharmacologic characteristics that reduce
      oropharyngeal exposure to active drug while maintaining efficacy comparable with
      currently available ICS.

PMID- 16629779
TI  - The use of quality-adjusted life-years in cost-effectiveness studies.

PMID- 16629780
TI  - Cost-effectiveness of asthma control: an economic appraisal of the GOAL study.
AB  - BACKGROUND: The Gaining Optimal Asthma ControL (GOAL) study has shown the
      superiority of a combination of salmeterol/fluticasone propionate (SFC) compared
      with fluticasone propionate alone (FP) in terms of improving guideline defined
      asthma control. METHODS: Clinical and economic data were taken from the GOAL
      study, supplemented with data on health related quality of life, in order to
      estimate the cost per quality adjusted life year (QALY) results for each of three
      strata (previously corticosteroid-free, low- and moderate-dose corticosteroid
      users). A series of statistical models of trial outcomes was used to construct
      cost effectiveness estimates across the strata of the multinational GOAL study
      including adjustment to the UK experience. Uncertainty was handled using the non
      parametric bootstrap. Cost-effectiveness was compared with other treatments for
      chronic conditions. RESULT: Salmeterol/fluticasone propionate improved the
      proportion of patients achieving totally and well-controlled weeks resulting in a
      similar QALY gain across the three strata of GOAL. Additional costs of treatment
      were greatest in stratum 1 and least in stratum 3, with some of the costs offset
      by reduced health care resource use. Cost-effectiveness by stratum was 7600 pound
      (95% CI: 4800-10,700 pound) per QALY gained for stratum 3; 11,000 pound (8600
      14,600 pound) per QALY gained for stratum 2; and 13,700 pound (11,000-18,300
      pound) per QALY gained for stratum 1. CONCLUSION: The GOAL study previously
      demonstrated the improvement in total control associated with the use of SFC
      compared with FP alone. This study suggests that this improvement in control is
      associated with cost-per-QALY figures that compare favourably with other uses of
      scarce health care resources.

PMID- 16629781
TI  - Anti-inflammatory effects of once daily low dose inhaled ciclesonide in mild to
      moderate asthmatic patients.
AB  - BACKGROUND: Ciclesonide exhibits clinical efficacy at 160 microg (ex-actuator)
      once daily but the anti-inflammatory effects at this dose are not known. We
      wished to know whether 4 weeks therapy with ciclesonide pMDI 160 microg once
      daily in the morning exhibited significant anti-inflammatory effects. METHODS:
      Seventeen patients with mild persistent asthma (FEV(1) 3.35 l) were recruited
      into a double-blind placebo-controlled randomized crossover study. Measurements
      were made after ciclesonide and placebo treatment as well as after run-in and
      washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary
      variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup). RESULTS:
      The mean (SEM) AMP bronchial challenge PC(20) following ciclesonide (140 (63)
      mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8)
      mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to
      an eightfold (CI: 5.3-12.0) for ciclesonide vs placebo. Likewise, there were
      significant improvements in exhaled NO levels and a significant reduction in
      induced sputum eosinophil cell counts. CONCLUSION: We have shown that inhaled
      ciclesonide given at 160 microg once daily in the morning exhibits significant
      anti-inflammatory effects that are in keeping with the previously described
      clinical effects.

PMID- 16629782
TI  - Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with
      asthma.
AB  - BACKGROUND: PTGDR gene has been identified as an asthma-susceptibility gene.
      Recently, functional genetic variants have been associated with asthma. The
      objective of this work was to study -549T>C, -441C>T and -197T>C PTGDR promoter
      polymorphisms in a Spanish population. METHODS: In this study, 197 Caucasian
      individuals were included. Asthma was specialist-physician diagnosed according to
      the American Thoracic Society (ATS) criteria and classified following the Global
      Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all
      patients. The polymorphisms were analyzed by direct sequencing. RESULTS: -197T>C
      polymorphism was significantly associated with asthma [Fisher's P-value = 0.007,
      Monte Carlo P-value (10(4) simulations) = 0.004]. Multivariate analysis adjusted
      for age and sex confirmed this association with an increased risk of asthma (OR,
      3.06; 95% CI, 1.28-7.32; P-value = 0.012). CCT CCC diplotype was associated with
      asthma (P-value < 0.0001; OR, 1.15; 95% CI, 1.07-1.23), specifically with
      allergic asthma (P-value < 0.0001). CCT CCC diplotype is unambiguous. All
      individuals carrying this diplotype had asthma. CONCLUSION: We identified a
      specific promoter variant of PTGDR that could be associated with asthma. This
      diplotype is a combination of the two highest transcriptional efficiency
      haplotypes, recently described. Our in vivo results would support for the first
      time what was demonstrated in vitro about high-transcriptional efficiency PTGDR
      haplotypes in asthma.

PMID- 16629783
TI  - Asthma during the primary school ages--prevalence, remission and the impact of
      allergic sensitization.
AB  - BACKGROUND: Childhood is the most important time for asthma development. The aims
      of this study were to study changes in prevalence of asthma and wheeze, remission
      of asthma and changes in risk factor pattern from age 7-8 to age 11-12 in a
      cohort of school children. METHODS: In 1996, 3525 children aged 7-8 years in
      northern Sweden were invited to participate in a parental expanded ISAAC
      questionnaire survey. The cohort has been followed prospectively with yearly
      follow-ups to age 11-12, with a 97% yearly response rate. Skin prick tests were
      conducted at age 7-8 and 11-12. RESULTS: The prevalence of physician-diagnosed
      asthma increased from 5.7% at age 7-8 to 7.7% at age 11-12. Life-time prevalence
      of wheeze was 34.7% at age 11-12. The remission of asthma was 10% yearly and
      inversely related to allergic sensitization. Relapses were common, and remission
      persisting throughout the observation period was 5% yearly. Allergic
      sensitization was associated with current asthma at age 7-8 [adjusted odds ratio
      (OR) 4.9 (95% confidence interval (CI) 3.3-7.3)] and when the children were 4
      years older [OR 5.6 (3.9-8.2)]. A family history of asthma was associated with
      current asthma at age 7-8 [OR 3.0 (2.1-4.5)] and 11-12 (OR 2.8 [2.0-3.9]). Ever
      having lived with a cat was significantly negatively associated with current
      asthma. CONCLUSIONS: The prevalence of asthma increased continuously during the
      primary school ages. Among several significant risk factors, allergic
      sensitization and a family history of asthma were the most important. With
      increasing age many known risk factors lost significance. Remission was inversely
      related to allergic sensitization.

PMID- 16629784
TI  - Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7
      year old Swiss children from 1992 to 2001.
AB  - BACKGROUND: Changing occurrence rates of asthma, allergic rhinitis and atopic
      dermatitis are of public health concern and require surveillance. Changes in
      prevalence rates of these atopic diseases were monitored during 10 years and
      their trend with time was determined taking into account the influence of
      personal and environmental risk factors. METHODS: Four cross-sectional surveys in
      5-7-year old children were performed in seven different communities in
      Switzerland between 1992 and 2001. Prevalence of respiratory and allergic
      symptoms and of affecting risk factors including parental environmental concern
      were assessed using a standardized parental questionnaire. RESULTS: A total of
      988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated,
      respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of
      asthma and hay fever symptoms remained quite stable over time (wheeze/past year:
      8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4%
      and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past
      year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of
      diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%).
      Stratified analysis by parental environmental concern and by parental atopy
      showed similar trends. Rates of atopic dermatitis symptoms showed significant
      increase in girls but stayed stable in boys. CONCLUSION: Results of these four
      consecutive surveys suggest that the increase in prevalence of asthma and hay
      fever in 5-7-year old children living in Switzerland may have ceased. However,
      symptoms of atopic dermatitis may still be on the rise, especially among girls.

PMID- 16629785
TI  - Gas cooking, kitchen ventilation, and asthma, allergic symptoms and sensitization
      in young children--the PIAMA study.
AB  - BACKGROUND: Several studies reported inconsistent associations between using gas
      for cooking and respiratory symptoms or lung function in children. Kitchen
      ventilation characteristics may modify the relationship between gas cooking and
      respiratory health. The aim of this study was to investigate the effect of
      kitchen ventilation (while cooking) on the relationship between gas cooking,
      combustion product dispersal, and respiratory and allergic outcomes in children.
      METHODS: Data on respiratory and allergic symptoms and diagnoses were collected
      by yearly questionnaires in a population of over 3000 children participating in a
      birth cohort study on development of allergy and asthma. At 4 years of age, a sub
      sample of 647 children provided blood samples for antibody testing. Data on gas
      cooking and kitchen ventilation were collected when the children were 5 years
      old. Based on these data a model was constructed to determine the chance of
      accumulation of combustion products (CACP) in the kitchen. RESULTS: No
      relationship was found between gas cooking and any of the respiratory or allergy
      outcomes except nasal symptoms. The overall results did not change when the
      'CACP' was used as exposure variable instead, while the association for nasal
      symptoms decreased to borderline significance. CONCLUSION: Our results suggest
      that gas cooking per se is associated with nasal symptoms in young children and
      not with the other respiratory symptoms that were investigated. Taking kitchen
      ventilation characteristics into account did not lead to different conclusions in
      this population where, according to the classification system, the majority of
      households using gas for cooking have insufficient kitchen ventilation.

PMID- 16629786
TI  - Attenuation of human lung mast cell degranulation by bronchial epithelium.
AB  - BACKGROUND: Human lung mast cells (HLMC) lie in close proximity to the bronchial
      epithelium in asthma and adhere with high affinity to bronchial epithelial
      monolayers in vitro. We investigated the consequences of this adhesive
      interaction on HLMC activation in response to Fc epsilon RI cross-linking.
      METHODS: Human lung mast cells were cultured with the bronchial epithelial cell
      line BEAS-2B or plastic control for either 30 min or 16 h and then activated with
      anti-IgE. Histamine was measured by radioenzymatic assay. RESULTS: After co
      culture for 30 min, IgE-dependent histamine release from HLMC was identical on
      both BEAS-2B and plastic. After 16 h of co-culture, there was a marked decrease
      in constitutive and IgE-dependent histamine release from HLMC cultured on BEAS-2B
      compared with those cultured on plastic or fibronectin. In contrast, the
      Ca(2+)/ATPase inhibitor thapsigargin produced concentration-dependent histamine
      release that was significantly increased on BEAS-2B compared with plastic. IgE
      dependent degranulation was not significantly affected by BEAS-2B-conditioned
      medium. CONCLUSIONS: BEAS-2B bronchial epithelial cells attenuate IgE-dependent
      but not thapsigargin-induced histamine release from HLMC. The differential effect
      with anti-IgE compared with thapsigargin suggests that the mechanism includes
      interference with the proximal Fc epsilon RI signalling pathway.

PMID- 16629787
TI  - Confirmation of association of IL-15 with pediatric asthma and comparison of
      different controls.
AB  - BACKGROUND: Interleukin (IL)-15 is an important mediator in chronic inflammatory
      diseases. Recently, we have described the association of IL-15 haplotypes with
      bronchial asthma. Asthma genetics is highly complex - about every second
      candidate gene is not confirmed in consecutive studies. We were interested in
      whether association of asthma with IL-15 holds in a second population.
      Furthermore, we sought to investigate the effect of different controls. METHODS:
      Five IL-15 polymorphisms were genotyped on the German Multicenter Allergy Study
      (MAS) cohort consisting of 886 children who were followed up from birth to 10
      years of age. At 10 years of age, 96 were found to be asthmatic. MAS children who
      never had any wheezing symptoms (n = 576), who were never diagnosed with asthma
      (n = 790) and 129 super controls who had never had any atopic disorder were used
      as controls. Finally, 270 randomly chosen adults served as controls. RESULTS:
      Association was confirmed with single polymorphism and haplotypes. The super
      controls showed the highest difference to the asthmatics regarding haplotype
      frequencies. However, the effect escaped statistical significance, most likely
      because of the small sample size. CONCLUSION: Association of IL-15 with asthma
      was confirmed. Although super controls might be the most suitable, more numbers
      are needed. This might hamper the value of these controls especially when
      investigating common diseases.

PMID- 16629788
TI  - Diesel exhaust particles enhance T-cell activation in severe asthmatics.
AB  - Prevalence of asthma is increasing in westernized countries. Epidemiological
      studies showed the impact of traffic pollution on the triggering of asthma
      symptoms and exacerbations, and this effect is mainly attributed to the
      polycyclic aromatic hydrocarbon core of diesel exhaust particles (DEP). However,
      although DEP induce IgE synthesis, little is known of their role on T-cell
      activation, the main cells orchestrating asthma inflammation. We assessed the
      effect of DEP on T-cell activation in severe uncontrolled asthmatics during (n =
      13) and outside (n = 19) exacerbations. Results were compared with data obtained
      in healthy controls (n = 14). Peripheral blood mononuclear cells were cultured in
      the presence of low-dose DEP. T-cell activation markers, CD69 and CD25,
      interleukin-4 (IL-4) and interferon (IFN)-gamma production and T-cell
      proliferation were assessed by flow cytometry. DEP exposure increased the
      proportion of CD3+CD69+ T cells in all subjects. The proportion of CD25+ T cells
      increased under DEP stimulation in the exacerbation group only. IFN-gamma- and IL
      4-producing T cells increased in both asthmatic groups, especially during
      exacerbations, but not in controls. This effect was more pronounced for IL-4. In
      response to DEP stimulation, T-cell proliferation increased in higher proportion
      in asthmatics compared with controls. These results show that DEP activate T
      cells in asthmatics only, with a higher effect during exacerbations. This is in
      keeping with epidemiological data which demonstrated that DEP trigger respiratory
      symptoms in asthmatics but not in controls. The higher effect of DEP in
      exacerbated asthmatics suggests that uncontrolled asthma is a risk factor for
      aggravation under exposure to traffic pollutants.

PMID- 16629789
TI  - Human airway and peripheral blood eosinophils enhance Th1 and Th2 cytokine
      secretion.
AB  - BACKGROUND: The effector function of eosinophils involves their release of toxic
      granule proteins, reactive oxygen species, cytokines, and lipid mediators. Murine
      studies have demonstrated that eosinophils can also enhance T cell function.
      Whether human eosinophils, in particular, airway eosinophils, have similar
      immunoregulatory activity has not been fully investigated. The aim of this study
      was to determine whether human blood and airway eosinophils can contribute to Th1
      and Th2 cytokine generation from CD4+ T cells stimulated with superantigen.
      METHODS: Eosinophils were obtained from blood or bronchoalveolar lavage fluid 48
      h after segmental allergen bronchoprovocation. Purified eosinophils were co
      cultured with autologous CD4+ blood T cells in the presence of staphylococcal
      enterotoxin B (SEB). Cytokine levels in the supernatant fluid were determined by
      enzyme-linked immunosorbent assay (ELISA). Eosinophil expression of major
      histocompatibility complex (MHC) class II and co-stimulatory molecules was
      assessed by flow cytometry before culture, 24 h after granulocyte-macrophage
      colony-stimulating factor (GM-CSF) stimulation, and 24 h after co-culture with
      CD4+ T cells and SEB. RESULTS: Interleukin (IL)-5, IL-13, and interferon (IFN)
      gamma generation increased when CD4+ T cells were co-cultured with either blood
      or airway eosinophils in the presence of SEB. The ability of eosinophils to
      enhance cytokine generation was independent of their source (blood vs airway),
      activation by GM-CSF, or detectable expression of human leukocyte antigen (HLA)
      DR, CD80, or CD86. CONCLUSION: Our data demonstrate that SEB-induced generation
      of Th1 and Th2 cytokines is increased in the presence of human blood and airway
      eosinophils. Thus, eosinophils can have an immunoregulatory function in pathogen
      associated allergic diseases such as atopic dermatitis, chronic sinusitis, and
      asthma exacerbations.

PMID- 16629790
TI  - Surfactant protein levels in bronchoalveolar lavage after segmental allergen
      challenge in patients with asthma.
AB  - BACKGROUND: Allergic asthma is associated with airway inflammation and
      dysfunction of pulmonary surfactant. Because surfactant proteins (SP) account for
      immunomodulatory functions as well as biophysical functions, we hypothesized that
      the allergic response in asthma might be accompanied by a dysregulation of SPs.
      METHODS: We measured levels of SP-A, SP-B, SP-C and SP-D by enzyme-linked
      immunosorbent assay in bronchoalveolar lavage (BAL) fluid of 23 asthma patients
      and 10 healthy control subjects under well-controlled conditions before and 24 h
      after segmental allergen provocation. These data were related to surfactant
      function, Th(2) cytokine levels in BAL fluid and to the degree of eosinophilic
      inflammation. RESULTS: In patients with asthma, allergen challenge increased BAL
      levels of SP-B, SP-C and SP-D while SP-A was decreased. For SP-B and SP-D, a
      moderate increase was also observed after saline challenge. In contrast, no
      alterations were observed in healthy control subjects. Levels of SP-B and SP-C in
      asthmatics correlated with the ratio of small to large surfactant aggregates
      (SA/LA ratio) and correlated negatively with BAL surface activity. Furthermore,
      increased SP-C but not SP-B levels after allergen challenge correlated with
      eosinophil numbers, interleukin (IL)-5, and IL-13 in BAL while increased SP-D
      levels only correlated with eosinophil numbers. CONCLUSIONS: This study
      demonstrates significant alterations of all SPs in BAL fluid after allergen
      challenge of which SP-C was most closely related to surfactant dysfunction and
      the degree of the allergic inflammation.

PMID- 16629791
TI  - The effect of salt chamber treatment on bronchial hyperresponsiveness in
      asthmatics.
AB  - BACKGROUND: Randomized controlled trials are needed to evaluate the effects of
      complementary treatments in asthma. This study assessed the effect of salt
      chamber treatment as an add-on therapy to low to moderate inhaled steroid therapy
      in asthma patients with bronchial hyperresponsiveness (BHR). METHODS: After a 2
      week baseline period, 32 asthma patients who exhibited BHR in the histamine
      inhalation challenge were randomized: 17 to 2-week active treatment, during which
      salt was fed to the room by a salt generator, and 15 to placebo. The salt chamber
      treatment lasted 40 min and was administered five times a week. RESULTS: Median
      provocative dose causing a decrease of 15% in Fev(1) (PD(15)FEV(1)) [corrected]
      increased significantly in the active group (P = 0.047) but not in the placebo
      group. The difference in changes between the active and placebo groups was
      significant (P = 0.02). Nine patients (56%) in the active group and two patients
      (17%) in the placebo group exhibited at least one doubling dose decrease in BHR
      (P = 0.040). Six patients (38%) in the active group and none in the placebo group
      became non-hyperresponsive (P = 0.017). Neither the peak expiratory flow (PEF)
      values measured just before and after the treatment, nor FEV(1) values measured
      before the histamine challenges, changed. The reduction in BHR was not caused by
      changes in the baseline lung function. CONCLUSIONS: Salt chamber treatment
      reduced bronchial hyperresponsiveness as an add-on therapy in asthmatics with a
      low to moderate dose of inhaled steroids. The possibility that salt chamber
      treatment could serve as a complementary therapy to conventional medication
      cannot be excluded.

PMID- 16629792
TI  - Type-IV sensitization profile of individuals with atopic eczema: results from the
      Information Network of Departments of Dermatology (IVDK) and the German Contact
      Dermatitis Research Group (DKG).
AB  - The role of atopic eczema (AE) as risk factor for the development of allergic
      contact dermatitis is discussed controversially, as well as its influence on
      patch test results due to increased irritability. In this study, we analysed the
      pattern of positive patch test results to most frequent contact allergens in
      patients with AE (n = 9020) and age matched nonatopic (n = 15,263) individuals.
      The pattern and the frequencies of the observed sensitizations did not differ
      greatly from nonatopic individuals. Bufexamac is an exception: in AE patients
      sensitization is observed three times more often. For the other substances tested
      only minor differences were detected. Moreover, the frequencies of single, double
      or polyvalent sensitizations were nearly identical between the two groups. The
      analysis of the anatomical sites of dermatitis shows differences between the
      groups: in AE patients, the face (7.2%) and hand dermatitis (6.6%) was more
      common, and leg dermatitis (4.0%) less common. Analysis of occupation, suspected
      allergen source, and accompanying factors revealed no major differences between
      the both groups. CONCLUSION: The chronic and long-term exposure to external drugs
      and emollients presumably carries a risk for sensitization against specific
      contact allergens in AE patients. However, the sensitization of contact allergens
      differs surprisingly little between patients with or without AE.

PMID- 16629793
TI  - Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish
      population.
AB  - BACKGROUND: Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing,
      inflammatory skin disease resulting from multiplex interactions between genes and
      environmental factors. We have previously found several loci showing suggestive
      linkage on chromosomes 3q14, 13q14, 15q14-15 and 17q21, and weaker linkage to
      chromosomes 1p32, 4q24-26 and 21q21 in 109 Swedish families. METHODS: In order to
      confirm the linkage to chromosome 21, we carried out a replication linkage
      analysis with additional microsatellite markers on chromosome 21 in another set
      of 295 families. RESULTS: In the extended material, the Z-score was 2.40 (P < 7.4
      x 10(-4)) in the region 21q21 for a semi-quantitative variable measurement; the
      severity of AD. When combining the two data sets into 404 families and
      stratifying according to asthma status, suggestive linkage was found only in the
      group of AD patients who also had asthma (Z-score 2.45, P < 7.4 x 10(-4) and
      2.69, P < 7.4 x 10(-4)) in two different regions. CONCLUSIONS: Our results
      suggest that 21q21 could contain a susceptibility gene modulating the severity of
      AD especially in combination with asthma.

PMID- 16629794
TI  - Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone
      acetonide 0.1%.
AB  - BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction
      of eczema by inhalant allergens in atopic dermatitis patients. We studied the
      effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of
      patients with atopic dermatitis. METHODS: Nonlesional skin of the back of
      patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with
      tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative
      control and triamcinolone acetonide 0.1% ointment as positive control. Twenty
      four hours after the last APT application, samples were taken from the three
      treated areas (t = 0 and 24 h) for immunohistochemical analysis. RESULTS:
      Pretreatment with tacrolimus ointment did not suppress nonlesional skin
      infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did
      not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx
      of T cells, eosinophils, dendritic cells, CD64+ and Fc epsilon RI-positive cells
      was present compared with placebo. Only CD36+ and CD68-positive cells were
      inhibited compared with placebo. All cell types were significantly inhibited in
      triamcinolone acetonide-treated sites compared with placebo. CONCLUSIONS:
      Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in
      patients with atopic dermatitis.

PMID- 16629795
TI  - Low prevalence of the intrinsic form of atopic dermatitis among adult patients.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease
      commonly associated with respiratory allergies such as rhinitis and asthma, and a
      high serum level of IgE. In contrast to the 'classic' IgE-mediated allergic
      (extrinsic) form of AD, approximately 20% of the patients are reported to show
      normal IgE levels, lack of sensitizations towards environmental allergens, and
      absence of associated respiratory allergies. Accordingly, these patients are
      assigned to a nonallergic (intrinsic) form of the disease. OBJECTIVES: In order
      to define these two forms of AD more closely, 259 adult patients with AD were
      investigated. RESULTS: After a thorough diagnostic workup there were 18 patients
      (6.9%), who fulfilled the criteria of intrinsic AD. After follow-up, four
      additional patients had developed respiratory allergies or IgE-mediated
      sensitizations resulting in an overall proportion for intrinsic AD of 5.4%.
      CONCLUSIONS: Based on these figures the nature and relevance of the intrinsic
      form of AD deserves further evaluation.

PMID- 16629796
TI  - The performance of a component-based allergen-microarray in clinical practice.
AB  - BACKGROUND: Currently, the diagnosis of IgE-mediated allergy is based on allergen
      specific history and diagnostic procedures using natural allergen extracts for in
      vivo and in vitro tests. OBJECTIVE: The aim of the study was to comparatively
      analyse a new component-based allergen-microarray and the 'quasi-standard'
      ImmunoCAP for their clinical relevance in patients with allergic
      rhinoconjunctivitis to five aeroallergens [house dust mite (HDM), cat dander,
      birch, grass and mugwort pollen] in a prospective, double-centre study. METHODS:
      We enrolled 120 subjects at the two study centres. Allergic patients were defined
      as having an allergen-specific history plus a concomitant positive skin-prick
      test (SPT) to natural allergen extracts and specific serum IgE was measured by
      both methods. Each allergen was analysed separately. RESULTS: The microarray
      performed equally well in receiver-operating characteristic curve (ROC) analyses
      when compared with the CAP in cat (23 allergic vs 97 non-allergic, ROC area under
      the curve microarray 0.950 vs CAP 0.894, P = 0.211), birch (31/89, 0.908 vs
      0.878, P = 0.483) and grass pollen (47/73, 0.923 vs 0.915, P = 0.770). It was
      slightly less sensitive in HDM-allergic subjects (26 allergic vs 94 non-allergic,
      ROC area microarray 0.808 vs CAP 0.911, P = 0.053) and displayed a reduced
      sensitivity in the mugwort pollen-allergic patients (17/103, 0.723 vs 0.879, P =
      0.032). CONCLUSIONS: Component-based testing and the whole-allergen CAP are
      equally relevant in the diagnosis of grass-, birch- and cat-allergic patients.
      Although slightly less sensitive, the microarray is sufficient for the diagnosis
      of HDM-allergic patients, but needs alternative and/or additional components for
      detecting mugwort allergy.

PMID- 16629797
TI  - Nonlinear relations between house dust mite allergen levels and mite
      sensitization in farm and nonfarm children.
AB  - BACKGROUND: Low sensitization rates to common allergens have been observed in
      farm children, which might be due to high exposure to microbial agents. It is not
      known how microbial agents modify the association between specific allergen
      exposure and sensitization. OBJECTIVE: To examine the relations between house
      dust mite allergen exposure and mite sensitization in farm and nonfarm children
      and to assess the effects of microbial agents levels on this association.
      METHODS: Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and
      Dermatophagoides farinae (Der f 1), endotoxin, beta(1,3)-glucans and fungal
      extracellular polysaccharides were measured in mattress dust of 402 children
      participating in a cross-sectional study in five European countries. Mite
      allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4
      and 10.4 microg/g. Sensitization was assessed by measurement of allergen-specific
      immunoglobulin E against house dust mite. RESULTS: Prevalence ratios of mite
      sensitization for medium and high when compared with low mite allergen levels
      were 3.1 [1.7-5.7] and 1.4 [0.7-2.8] respectively. Highest mite sensitization
      rates at intermediate exposure levels were consistently observed across country
      (except for Sweden) and in both farm and nonfarm children. The shape of the dose
      response curve was similar for above and below median mattress microbial agent
      levels, but the 'sensitization peak' appeared to be lower for above median
      levels. CONCLUSIONS: Our data suggest a bell-shaped dose-response relationship
      between mite allergen exposure and sensitization to mite allergens. In
      populations with high microbial agent levels and low sensitization rates, the
      curve is shifted down.

PMID- 16629798
TI  - Prediction of asthma hazard of thiamine.

PMID- 16629799
TI  - Is toll-like receptor 6 or toll-like receptor 10 involved in asthma genetics--or
      both?

PMID- 16629800
TI  - Increased personal respirable endotoxin exposure with furry pets.

PMID- 16629801
TI  - What is a population? An empirical evaluation of some genetic methods for
      identifying the number of gene pools and their degree of connectivity.
AB  - We review commonly used population definitions under both the ecological paradigm
      (which emphasizes demographic cohesion) and the evolutionary paradigm (which
      emphasizes reproductive cohesion) and find that none are truly operational. We
      suggest several quantitative criteria that might be used to determine when groups
      of individuals are different enough to be considered 'populations'. Units for
      these criteria are migration rate (m) for the ecological paradigm and migrants
      per generation (Nm) for the evolutionary paradigm. These criteria are then
      evaluated by applying analytical methods to simulated genetic data for a finite
      island model. Under the standard parameter set that includes L = 20 High mutation
      (microsatellite-like) loci and samples of S = 50 individuals from each of n = 4
      subpopulations, power to detect departures from panmixia was very high (
      approximately 100%; P < 0.001) even with high gene flow (Nm = 25). A new method,
      comparing the number of correct population assignments with the random
      expectation, performed as well as a multilocus contingency test and warrants
      further consideration. Use of Low mutation (allozyme-like) markers reduced power
      more than did halving S or L. Under the standard parameter set, power to detect
      restricted gene flow below a certain level X (H(0): Nm < X) can also be high,
      provided that true Nm < or = 0.5X. Developing the appropriate test criterion,
      however, requires assumptions about several key parameters that are difficult to
      estimate in most natural populations. Methods that cluster individuals without
      using a priori sampling information detected the true number of populations only
      under conditions of moderate or low gene flow (Nm < or = 5), and power dropped
      sharply with smaller samples of loci and individuals. A simple algorithm based on
      a multilocus contingency test of allele frequencies in pairs of samples has high
      power to detect the true number of populations even with Nm = 25 but requires
      more rigorous statistical evaluation. The ecological paradigm remains challenging
      for evaluations using genetic markers, because the transition from demographic
      dependence to independence occurs in a region of high migration where genetic
      methods have relatively little power. Some recent theoretical developments and
      continued advances in computational power provide hope that this situation may
      change in the future.

PMID- 16629802
TI  - The ruddy duck Oxyura jamaicensis in Europe: natural colonization or human
      introduction?
AB  - Native to North America, ruddy ducks Oxyura jamaicensis now occur in 21 countries
      in the western Palaearctic (including Iceland) and their expanding population
      threatens the native white-headed duck, Oxyura leucocephala, through
      hybridization and possibly competition for food and nest sites. We used
      mitochondrial DNA sequences and nuclear microsatellites to test whether the
      European ruddy duck population is descended solely from the captive population in
      the UK, which traces to seven individuals imported from the USA in 1948, or,
      alternatively, has been augmented by natural dispersal of birds from North
      America. Limited genetic diversity in the European population is consistent with
      a founder population as small as seven birds. In addition, shifts in allele
      frequencies at several loci, presumably due to genetic drift in the founding
      population, result in significant differentiation between the European and North
      American populations. Despite the recent separation of these populations, almost
      all individuals could be unambiguously assigned based on their composite
      genotypes, to one of two distinct populations, one comprising all of the European
      ruddy ducks we sampled (including those from Iceland and captive birds in the UK)
      and the other comprising all North American samples. Our results confirm that the
      European ruddy duck population is likely to derive solely from the captive
      population in the UK and we find no evidence of recent arrivals from North
      America or of admixture between ruddy ducks from Europe and North America.

PMID- 16629803
TI  - Widespread gene flow and high genetic variability in populations of water voles
      Arvicola terrestris in patchy habitats.
AB  - Theory predicts that the impact of gene flow on the genetic structure of
      populations in patchy habitats depends on its scale and the demographic
      attributes of demes (e.g. local colony sizes and timing of reproduction), but
      empirical evidence is scarce. We inferred the impact of gene flow on genetic
      structure among populations of water voles Arvicola terrestris that differed in
      average colony sizes, population turnover and degree of patchiness. Colonies
      typically consisted of few reproducing adults and several juveniles. Twelve
      polymorphic microsatellite DNA loci were examined. Levels of individual genetic
      variability in all areas were high (H(O) = 0.69-0.78). Assignments of juveniles
      to parents revealed frequent dispersal over long distances. The populations
      showed negative F(IS) values among juveniles, F(IS) values around zero among
      adults, high F(ST) values among colonies for juveniles, and moderate, often
      insignificant, F(ST) values for parents. We inferred that excess heterozygosity
      within colonies reflected the few individuals dispersing from a large area to
      form discrete breeding colonies. Thus pre-breeding dispersal followed by rapid
      reproduction results in a seasonal increase in differentiation due to local
      family groups. Genetic variation was as high in low-density populations in patchy
      habitats as in populations in continuous habitats used for comparison. In
      contrast to most theoretical predictions, we found that populations living in
      patchy habitats can maintain high levels of genetic variability when only a few
      adults contribute to breeding in each colony, when the variance of reproductive
      success among colonies is likely to be low, and when dispersal between colonies
      exceeds nearest-neighbour distances.

PMID- 16629804
TI  - Domestication and the distribution of genetic variation in wild and cultivated
      populations of the Mesoamerican fruit tree Spondias purpurea L. (Anacardiaceae).
AB  - Domestication occurs as humans select and cultivate wild plants in agricultural
      habitats. The amount and structure of variation in contemporary cultivated
      populations has been shaped, in part, by how genetic material was transferred
      from one cultivated generation to the next. In some cultivated tree species,
      domestication involved a shift from sexually reproducing wild populations to
      vegetatively propagated cultivated populations; however, little is known about
      how domestication has impacted variation in these species. We employed AFLP data
      to explore the amount, structure, and distribution of variation in clonally
      propagated domesticated populations and sexually reproducing wild populations of
      the Neotropical fruit tree, Spondias purpurea (Anacardiaceae). Cultivated
      populations from three different agricultural habitats were included: living
      fences, backyards, and orchards. AFLP data were analysed using measures of
      genetic diversity (% polymorphic loci, Shannon's diversity index, Nei's gene
      diversity, panmictic heterozygosity), population structure (F(ST) analogues), and
      principal components analyses. Levels of genetic variation in cultivated S.
      purpurea populations are significantly less than variation found in wild
      populations, although the amount of diversity varies in different agricultural
      habitats. Cultivated populations have a greater proportion of their genetic
      variability distributed among populations than wild populations. The genetic
      structure of backyard populations resembles that of wild populations, but living
      fence and orchard populations have 1/3 more variability distributed among
      populations, most likely a reflection of relative levels of vegetative
      reproduction. Finally, these results suggest that S. purpurea was domesticated in
      two distinct regions within Mesoamerica.

PMID- 16629805
TI  - When log-dwellers meet loggers: impacts of forest fragmentation on two endemic
      log-dwelling beetles in southeastern Australia.
AB  - Anthropogenic activities continue to cause massive fragmentation and reduction of
      forest area worldwide. With fragmentation and reduction of habitat recognized as
      the greatest threats to biodiversity, the implementation of improved, informed
      and conservation-based forestry practices is essential, and requires a greater
      understanding of the responses of different organisms to forest fragmentation.
      While genetic techniques can add invaluable insights to fragmentation studies
      they have rarely been employed, particularly for multiple species. In the present
      study, we combined genetic information, obtained from allozyme loci and anonymous
      single copy nuclear DNA markers, with ecological data to investigate the impacts
      of forest fragmentation on two log-dwelling beetles with different life
      histories, in an 'islands of bush in a sea of pine' model, at Tumut in New South
      Wales, Australia. Both the relatively mobile (i.e. has high dispersal ability
      and/or broad habitat range) Adelium calosomoides and the less mobile Apasis
      puncticeps showed reduced mobility and gene flow in fragmented compared to
      continuous forest: there was significantly greater isolation by distance and
      stronger local structure revealed by spatial autocorrelation in fragmented
      forest. Analysis of patch and species characteristics revealed that genetic and
      demographic structure may be influenced by log degradation class for both
      species, and number of potential dispersal barriers, distance from continuous
      forest and desiccation intolerance/moisture preference for Ap. puncticeps. Thus
      the pine plantation matrix poses a barrier or filter for gene flow and mobility
      in both beetle species.

PMID- 16629806
TI  - Microsatellite markers identify three lineages of Phytophthora ramorum in US
      nurseries, yet single lineages in US forest and European nursery populations.
AB  - Analysis of 12 polymorphic simple sequence repeats identified in the genome
      sequence of Phytophthora ramorum, causal agent of 'sudden oak death', revealed
      genotypic diversity to be significantly higher in nurseries (91% of total) than
      in forests (18% of total). Our analysis identified only two closely related
      genotypes in US forests, while the genetic structure of populations from European
      nurseries was of intermediate complexity, including multiple, closely related
      genotypes. Multilocus analysis determined populations in US forests reproduce
      clonally and are likely descendants of a single introduced individual. The 151
      isolates analysed clustered in three clades. US forest and European nursery
      isolates clustered into two distinct clades, while one isolate from a US nursery
      belonged to a third novel clade. The combined microsatellite, sequencing and
      morphological analyses suggest the three clades represent distinct evolutionary
      lineages. All three clades were identified in some US nurseries, emphasizing the
      role of commercial plant trade in the movement of this pathogen.

PMID- 16629807
TI  - Evidence for a large-scale population structure among accessions of Arabidopsis
      thaliana: possible causes and consequences for the distribution of linkage
      disequilibrium.
AB  - The existence of a large-scale population structure was investigated in
      Arabidopsis thaliana by studying patterns of polymorphism in a set of 71 European
      accessions. We used sequence polymorphism surveyed in 10 fragments of
      approximately 600 nucleotides and a set of nine microsatellite markers.
      Population structure was investigated using a model-based inference framework.
      Among the accessions studied, the presence of four groups was inferred using
      genetic data, without using prior information on the geographical origin of the
      accessions. Significant genetic isolation by geographical distance was detected
      at the group level, together with a geographical gradient in allelic richness
      across groups. These results are discussed with respect to the previously
      proposed scenario of postglacial colonization of Europe from putative glacial
      refugia. Finally, the contribution of the inferred structure to linkage
      disequilibrium among 171 pairs of essentially unlinked markers was also
      investigated. Linkage disequilibrium analysis revealed that significant
      associations detected in the whole sample were mainly due to genetic
      differentiation among the inferred groups. We discuss the implication of this
      finding for future association studies in A. thaliana.

PMID- 16629808
TI  - Genetic relationships among marine and freshwater populations of the European
      three-spined stickleback (Gasterosteus aculeatus) revealed by microsatellites.
AB  - To assess the population genetic structure of the three-spined stickleback,
      Gasterosteus aculeatus, variability at 18 microsatellite loci was examined in
      1724 individuals from 74 locations covering most of the species distribution
      range in Europe. The results revealed high overall degree of differentiation
      (F(ST) = 0.21) but contrasting level of divergence and genetic variability
      between habitat types. Marine populations were genetically relatively uniform
      even across great geographical distances as compared to substantial
      differentiation among freshwater populations. Analysis of molecular variance
      indicated low but significant (2.7%) variation in allele frequencies between
      geographical regions, but a negligible effect of habitat type (0.2%). The
      phylogenetic pattern was not explained by habitat type, but a weak signal of
      populations clustering according to geographical or water system origin was
      found. The results support the view that three-spined stickleback marine
      ancestors colonized northern European fresh waters during the postglacial marine
      submergence c. 10,000 years ago, whereas in the Mediterranean region colonization
      probably dates back to the Pleistocene. The independent origins of river and lake
      populations indicate that they originate from multiple colonizations rather than
      sharing common ancestry. In the continuous marine environment, the low degree of
      differentiation among populations can be explained by gene flow among
      subpopulations and large effective population size buffering divergence in
      neutral markers. In contrast, among postglacially established freshwater
      populations differentiation appears to be driven by genetic drift and isolation.
      The stepwise mutations appear to have contributed to the population
      differentiation in the southern part of the three-spined stickleback distribution
      range.

PMID- 16629809
TI  - Inferring population history from fine-scale spatial genetic analysis in Oryza
      rufipogon (Poaceae).
AB  - Determining the genetic structure of an in situ conserved population can provide
      insight into the dynamics of population genetic processes associated with
      successful plant conservation. We used 21 microsatellite loci to analyse the
      genetic relationships among individuals (n = 813) collected from a small Oryza
      rufipogon population conserved since 1993 in Hunan Province of China. The
      analysis revealed four distinct genetic subpopulations (F(ST) = 0.145) without
      geographic isolation. One subpopulation was composed of possible introgressed
      individuals, two subpopulations were composed of seed recruits and their
      descendants, and the fourth subpopulation consisted of reintroduced individuals,
      seed recruits and their descendants. Positive spatial genetic structures were
      detected by spatial autocorrelation statistics at the population (c. 63 m) and
      subpopulation levels (11-30 m), but the degree of autocorrelation was stronger at
      the population level. These results showed that prejudging the cryptic structure
      is important before autocorrelation analysis for the entire population. Our study
      suggests that population history can be a significant determinant on population
      structure for plant restoration projects.

PMID- 16629810
TI  - Genetic variation and population differentiation in the lichen-forming ascomycete
      Xanthoria parietina on the island Storfosna, central Norway.
AB  - Genetic diversity and fine-scale population structure in the lichen-forming
      ascomycete Xanthoria parietina was investigated using sequence variation in part
      of the intergenic spacer (IGS) and the complete internal transcribed spacer (ITS)
      regions of the nuclear ribosomal DNA. Sampling included 213 and 225 individuals,
      respectively, from seven populations in two different habitats, bark and rock, on
      the island Storfosna off the central west coast of Norway. Both markers revealed
      significant variation and a total of 10 IGS and 16 ITS haplotypes were found.
      There were no signs of significant positive spatial autocorrelation at any
      spatial size class down to 10% of transect length, nor did we find significant
      deviations from neutrality or signs of historical population expansion. Analysis
      of molecular variance (amova) indicated that most of the genetic variance
      observed was within populations, but when populations were grouped according to
      habitat, more than a quarter of the variance was explained among groups. Pairwise
      comparisons of populations (F(ST), exact tests of population differentiation)
      revealed significant differentiation between populations in different habitats
      (on bark or rock), but not between populations in the same habitat. Haplotype
      networks show that internal and presumably old haplotypes are shared between
      habitats, whereas terminal haplotypes tend to be unique to a habitat, mostly
      bark. We interpret the observed pattern to mean that there is no evidence of
      restricted gene flow between populations in the same habitat at the present
      spatial scale (interpopulation distances one or a few kilometres). On the other
      hand, differentiation between habitats is considerable, which we attribute to
      restricted gene flow between habitats (habitat isolation). Evidence suggests that
      the observed differentiation did not evolve locally. Estimates of divergence time
      between populations in the respective habitats indicate that an ancestral
      population started to diverge at least 34,000 years ago but probably much further
      back in time.

PMID- 16629811
TI  - Genetic diversity, population structure, effective population size and
      demographic history of the Finnish wolf population.
AB  - The Finnish wolf population (Canis lupus) was sampled during three different
      periods (1996-1998, 1999-2001 and 2002-2004), and 118 individuals were genotyped
      with 10 microsatellite markers. Large genetic variation was found in the
      population despite a recent demographic bottleneck. No spatial population
      subdivision was found even though a significant negative relationship between
      genetic relatedness and geographic distance suggested isolation by distance. Very
      few individuals did not belong to the local wolf population as determined by
      assignment analyses, suggesting a low level of immigration in the population. We
      used the temporal approach and several statistical methods to estimate the
      variance effective size of the population. All methods gave similar estimates of
      effective population size, approximately 40 wolves. These estimates were slightly
      larger than the estimated census size of breeding individuals. A Bayesian model
      based on Markov chain Monte Carlo simulations indicated strong evidence for a
      long-term population decline. These results suggest that the contemporary wolf
      population size is roughly 8% of its historical size, and that the population
      decline dates back to late 19th century or early 20th century. Despite an
      increase of over 50% in the census size of the population during the whole study
      period, there was only weak evidence that the effective population size during
      the last period was higher than during the first. This may be caused by increased
      inbreeding, diminished dispersal within the population, and decreased immigration
      to the population during the last study period.

PMID- 16629812
TI  - Genetic and karyotypic structure in the shrews of the Sorex araneus group: are
      they independent?
AB  - The species of the common shrew (Sorex araneus) group are morphologically very
      similar but exhibit high levels of karyotypic variation. Here we used genetic
      variation at 10 microsatellite markers in a data set of 212 individuals mostly
      sampled in the western Alps and composed of five karyotypic taxa (Sorex
      coronatus, Sorex antinorii and the S. araneus chromosome races Cordon, Bretolet
      and Vaud) to investigate the concordance between genetic and karyotypic
      structure. Bayesian analysis confirmed the taxonomic status of the three sampled
      species since individuals consistently grouped according to their taxonomical
      status. However, introgression can still be detected between S. antinorii and the
      race Cordon of S. araneus. This observation is consistent with the expected low
      karyotypic complexity of hybrids between these two taxa. Geographically based
      cryptic substructure was discovered within S. antinorii, a pattern consistent
      with the different postglaciation recolonization routes of this species.
      Additionally, we detected two genetic groups within S. araneus notwithstanding
      the presence of three chromosome races. This pattern can be explained by the
      probable hybrid status of the Bretolet race but also suggests a relatively low
      impact of chromosomal differences on genetic structure compared to historical
      factors. Finally, we propose that the current data set (available at
      http://www.unil.ch/dee/page7010_en.html#1) could be used as a reference by those
      wanting to identify Sorex individuals sampled in the western Alps.

PMID- 16629813
TI  - Domestication history in the Medicago sativa species complex: inferences from
      nuclear sequence polymorphism.
AB  - DNA sequence polymorphism carries genealogical information and allows for testing
      hypotheses on selection and population history, especially through coalescent
      based analysis. Understanding the evolutionary forces at work in plant
      domestication and subsequent selection is of critical importance for the
      management of genetic resources. In this study, we surveyed DNA sequence
      diversity at two assumed neutral nuclear loci in the wild-domesticated species
      complex of alfalfa (Medicago sativa L.). A high level of polymorphism was
      detected. The domesticated pool contains on average 31% less diversity than the
      wild pool, but with a high heterogeneity among loci. Coalescent simulations of
      the domestication process showed that this result cannot be explained by assuming
      a constant population size but is rather consistent with a demographic bottleneck
      during domestication. A very low level of divergence was detected between the
      wild and the domesticated forms as well as between the related subspecies of the
      M. sativa species complex. However, the originality of the Spanish wild
      populations, already observed based on mitochondrial DNA polymorphism, was
      confirmed. These results, together with patterns of intrapopulation polymorphism,
      suggest that nuclear sequence polymorphism could be a promising tool,
      complementary to mitochondrial DNA and phenotypic evaluations, to investigate
      historical demographic and evolutionary processes.

PMID- 16629814
TI  - Phylogeographic structure and past history of the circum-Mediterranean species
      Tomicus destruens Woll. (Coleoptera: Scolytinae).
AB  - Phylogeographic studies are often focused on temperate European species with
      relict footholds in the Mediterranean region. Past climatic oscillations usually
      induced range contractions and expansions from refugial areas located in southern
      Europe, and spatial distribution of genetic diversity show that northward
      expansions were usually pioneer-like. Actually, few studies have focused on
      circum-Mediterranean species, which probably were not influenced in the same way
      by climatic oscillations. We present the phylogeography of the bark beetle
      Tomicus destruens, which is restricted to the whole Mediterranean basin and the
      Atlantic coasts of North Africa and Portugal. We systematically sequenced 617 bp
      of the mitochondrial genes COI and COII for 42 populations (N = 219). Analysis
      revealed 53 haplotypes geographically structured in two clades, namely eastern
      and western clades, that diverged during the Pleistocene. A contact zone was
      identified along the Adriatic coast of Italy. Interestingly, we found contrasting
      levels of genetic structure within each clade. The eastern group was
      characterized by a significant phylogeographic pattern and low levels of gene
      flow, whereas the western group barely showed a spatial structure in haplotype
      distribution. Moreover, the main pine hosts were different between groups, with
      the Aleppo-brutia complex in the east and the maritime pine in the west.
      Potential roles of host species, climatic parameters and geographical barriers
      are discussed and the phylogeographic patterns are compared to classical models
      of postglacial recolonization in Europe.

PMID- 16629815
TI  - Mitochondrial evidence for distinct phylogeographic units in the endangered
      Malagasy poison frog Mantella bernhardi.
AB  - Mantella bernhardi is an endemic species of Malagasy poison frog threatened by
      loss and fragmentation of its natural habitat and collection for the pet trade.
      It is classified as threatened according to the International Union for
      Conservation of Nature and Natural Resources (IUCN) categories and included in
      Appendix II of the Convention on the International Trade of Endangered Species
      (CITES). A recent survey has increased the known distributional range of the
      species from one to eight populations across southeastern Madagascar, but little
      is known about its biology and genetic diversity. Here we estimate inter- and
      intrapopulation mitochondrial genetic variation of four populations. Populations
      from the northern and southern parts of the distributional range showed a high
      degree of divergence (maximum of 11.35% in cytochrome b) and were recovered as
      reciprocally monophyletic groups. Nine haplotypes were detected in the northern
      and 12 in the southern populations. The population from Ranomafana National Park
      showed the lowest number of haplotypes and nucleotide diversity, and shared its
      most common haplotype with the second northern population from Tolongoina. All
      the other detected haplotypes were unique to each of the four populations. This
      suggests the existence of important barriers to gene flow, pre-dating human
      colonization of Madagascar at about 2000 years ago, in distinct contrast to other
      Mantella species that show a high degree of haplotype sharing throughout their
      range. The continued habitat fragmentation within the distribution range of M.
      bernhardi prevents any connection between its populations. Our data indicate the
      existence of at least two different management units for conservation in this
      species, corresponding to the North and South of its distribution range, and
      highlight the existence of strong regional endemism in southeastern Madagascar.

PMID- 16629816
TI  - Phylogeography of postglacial range expansion in Nigronia serricornis Say
      (Megaloptera: Corydalidae).
AB  - We have examined the effects of post-Wisconsinan glacial range expansion on the
      phylogeography of the saw-combed fishfly, Nigronia serricornis Say (Megaloptera:
      Corydalidae) because aquatic insects are under-represented in postglacial studies
      (and in phylogeography in general), and because the effects of ecological
      degradation on the population genetics of environmental indicator species like N.
      serricornis cannot be measured unless the underlying phylogeography is
      understood. Sequence data from a 630-base fragment of the mitochondrial
      cytochrome oxidase I (COI) gene were subjected to amova and nested clade analysis
      for 30 populations (n = 344) of N. serricornis. Both the amova and nested clade
      analysis revealed substantial population structure; 44.4% of the variance occured
      among populations. Three northward migrations are apparent: one from Tennessee
      into Illinois, Indiana, Wisconsin, Michigan and Ontario, a second that radiated
      eastward from Pennsylvania, and a third that moved along the coast from North
      Carolina into Connecticut, Massachusetts, Maine and then into New York. The
      latter two of these migrations were the result of contiguous range expansions,
      while the former expansion, out of Tennessee, appears to have been rapid with
      little gene flow from the source population. Additional clades included a group
      of haplotypes in central Kentucky that appear to have expanded along preglacial
      drainages, and clades in North Carolina and Georgia that have remained centrally
      located. Haplotype diversity decreased from south to north, a pattern that has
      been widely reported for animal and plant populations that expanded with the
      retreat of the Wisconsinan glaciation.

PMID- 16629817
TI  - Population genetic structure and demographic history of the endemic Formosan
      lesser horseshoe bat (Rhinolophus monoceros).
AB  - Intraspecific phylogenies can provide useful insights into how populations have
      been shaped by historical and contemporary processes. Taiwan formed around 5
      million years ago from tectonic uplift, and has been connected to mainland Asia
      several times since its emergence. A central mountain range runs north to south,
      bisecting the island, and potentially impedes gene flow along an east-west axis.
      The Formosan lesser horseshoe bat (Rhinolophus monoceros) is endemic to Taiwan,
      where it is found mainly at low altitude. To determine the population structure
      and the demographic and colonization history of this species, we examined
      variation in the mitochondrial DNA control region in 203 bats sampled at 26
      sites. We found very high haplotype and nucleotide diversity, which decreased
      from the centre to the south and north. Population differentiation followed a
      pattern of isolation by distance, though most regional genetic variance was
      attributable to differences between the relatively isolated southern population
      and those from other regions. A haplotype network was consistent with these
      findings and also suggested a southward colonization, followed by subsequent
      secondary contact between the south and other regions. Mismatch distributions
      were used to infer a past population expansion predating the last glacial
      maximum, and a neighbour-joining tree showed that R. monoceros formed a
      monophyletic grouping with respect to its sister taxa. Taken together, our
      results suggest that this taxon arose from a single period of colonization, and
      that demographic growth followed in the late Pleistocene. Current genetic
      structure reflects limited gene flow, probably coupled with stepwise colonization
      in the past. We consider explanations for the persistence of the species through
      multiple glacial maxima.

PMID- 16629818
TI  - A new method to estimate relatedness from molecular markers.
AB  - Four major problems can affect the efficiency of methods developed to estimate
      relatedness between individuals from information of molecular markers: (i) some
      of them are dependent on the knowledge of the true allelic frequencies in the
      base population; (ii) they assume that all loci are unlinked and in Hardy
      Weinberg and linkage equilibrium; (iii) pairwise methods can lead to incongruous
      assignations because they take into account only two individuals at a time; (iv)
      most are usually constructed for particular structured populations (only consider
      a few relationship classes, e.g. full-sibs vs. unrelated). We have developed a
      new approach to estimate relatedness that is free from the above limitations. The
      method uses a 'blind search algorithm' (actually simulated annealing) to find the
      genealogy that yield a co-ancestry matrix with the highest correlation with the
      molecular co-ancestry matrix calculated using the markers. Thus (i and ii) it
      makes no direct assumptions about allelic frequencies or Hardy-Weinberg and
      linkage equilibrium; (iii) it always provide congruent relationships, as it
      considers all individuals at a time; (iv) degrees of relatedness can be as
      complex as desired just increasing the 'depth' (i.e. number of generations) of
      the proposed genealogies. Computer simulations have shown that the accuracy and
      robustness against genotyping errors of this new approach is comparable to that
      of other proposed methods in those particular situations they were developed for,
      but it is more flexible and can cope with more complex situations.

PMID- 16629819
TI  - Genetic structure is influenced by landscape features: empirical evidence from a
      roe deer population.
AB  - The delimitation of population units is of primary importance in population
      management and conservation biology. Moreover, when coupled with landscape data,
      the description of population genetic structure can provide valuable knowledge
      about the permeability of landscape features, which is often difficult to assess
      by direct methods (e.g. telemetry). In this study, we investigated the genetic
      structuring of a roe deer population which recently recolonized a fragmented
      landscape. We sampled 1148 individuals from a 40 x 55-km area containing several
      putative barriers to deer movements, and hence to gene flow, namely a highway,
      rivers and several canals. In order to assess the effect of these landscape
      features on genetic structure, we implemented a spatial statistical model known
      as geneland which analyses genetic structure, explicitly taking into account the
      spatial nature of the problem. Two genetic units were inferred, exhibiting a very
      low level of differentiation (F(ST) = 0.008). The location of their boundaries
      suggested that there are no absolute barriers in this study area, but that the
      combination of several landscape features with low permeability can lead to
      population differentiation. Our analysis hence suggests that the landscape has a
      significant influence on the structuring of the population under study. It also
      illustrates the use of geneland as a powerful method to infer population
      structure, even in situations of young populations exhibiting low genetic
      differentiation.

PMID- 16629820
TI  - Age-independent telomere length predicts fitness in two bird species.
AB  - Telomeres are dynamic DNA-protein structures that form protective caps at the
      ends of eukaryotic chromosomes. Although initial telomere length is partly
      genetically determined, subsequent accelerated telomere shortening has been
      linked to elevated levels of oxidative stress. Recent studies show that short
      telomere length alone is insufficient to induce cellular senescence; advanced
      attrition of these repetitive DNA sequences does, however, reflect ageing
      processes. Furthermore, telomeres vary widely in length between individuals of
      the same age, suggesting that individuals differ in their exposure or response to
      telomere-shortening stress factors. Here, we show that residual telomere length
      predicts fitness components in two phylogenetically distant bird species:
      longevity in sand martins, Riparia riparia, and lifetime reproductive success in
      dunlins, Calidris alpina. Our results therefore imply that individuals with
      longer than expected telomeres for their age are of higher quality.

PMID- 16629821
TI  - Dispersal and genetic structure in the American marten, Martes americana.
AB  - Natal dispersal in a vagile carnivore, the American marten (Martes americana),
      was studied by comparing radio-tracking data and microsatellite genetic structure
      in two populations occupying contrasting habitats. The genetic differentiation
      determined among groups of individuals using F(ST) indices appeared to be weak in
      both landscapes, and showed no increase with geographical distance. Genetic
      structure investigated using pairwise genetic distances between individuals
      conversely showed a pattern of isolation by distance (IBD), but only in the
      population occurring in a homogeneous high-quality habitat, therefore showing the
      advantage of individual-based analyses in detecting within-population processes
      and local landscape effects. The telemetry study of juveniles revealed a
      leptokurtic distribution of dispersal distances in both populations, and
      estimates of the mean squared parent-offspring axial distance (sigma2) inferred
      both from the genetic pattern of IBD and from the radio-tracking survey showed
      that most juveniles make little contribution to gene flow.

PMID- 16629822
TI  - Multiple introductions promote range expansion of the mollusc Cyclope neritea
      (Nassariidae) in France: evidence from mitochondrial sequence data.
AB  - Since the 1970s, the nassariid gastropod Cyclope neritea has been extending its
      range north along the French Atlantic coasts from the Iberian Peninsula. This may
      be due to natural spread because of the recent warming of the northeastern
      Atlantic. However, human-mediated introductions related to shellfish culture may
      also be a probable explanation for this sudden range expansion. To examine these
      two hypotheses, we carried out a comprehensive study based on mitochondrial gene
      sequences (cytochrome oxidase I) of the five recently colonized French bays as
      well as 14 populations located in the recognized native range of the species.
      From a total of 594 individuals, we observed 29 haplotypes to split into three
      divergent clades. In the native range, we observed a low molecular diversity,
      strong genetic structure and agreement between geography and gene genealogies.
      Along the French coasts, we observed the opposite: high genetic diversity and low
      genetic structure. Our results show that recurrent human-mediated introductions
      from several geographical areas in the native range may be a source for the
      French Atlantic populations. However, despite the low dispersal ability of C.
      neritea, the isolation-by-distance pattern in France suggested that this
      gastropod may have been present (although unnoticed) on the French Atlantic
      coasts before the 1970s. As C. neritea shows characteristics of a cryptogenic
      species, the classification of Atlantic populations as either native or
      introduced is not straightforward. Cryptogenic species should be studied further
      to determine the status of new populations close to their recognized native
      range.

PMID- 16629824
TI  - Mechanism of action and structural requirements of constrained peptide inhibitors
      of RGS proteins.
AB  - Regulators of G-protein signaling (RGS) accelerate guanine triphosphate
      hydrolysis by Galpha-subunits and profoundly inhibit signaling by G protein
      coupled receptors. The distinct expression patterns and pathophysiologic
      regulation of RGS proteins suggest that inhibitors may have therapeutic
      potential. We previously reported the design of a constrained peptide inhibitor
      of RGS4 (1: Ac-Val-Lys-[Cys-Thr-Gly-Ile-Cys]-Glu-NH2, S-S) based on the structure
      of the Galphai switch 1 region but its mechanism of action was not established.
      In the present study, we show that 1 inhibits RGS4 by mimicking and competing for
      binding with the switch 1 region of Galphai and that peptide 1 shows selectivity
      for RGS4 and RGS8 versus RGS7. Structure-activity relationships of analogs
      related to 1 are described that illustrate key features for RGS inhibition.
      Finally, we demonstrate activity of the methylene dithioether-bridged peptide
      inhibitor, 2, to modulate muscarinic receptor-regulated potassium currents in
      atrial myocytes. These data support the proposed mechanism of action of peptide
      RGS inhibitors, demonstrate their action in native cells, and provide a starting
      point for the design of RGS inhibitor drugs.

PMID- 16629825
TI  - Aza-scanning of the potent melanocortin receptor agonist Ac-His-D-Phe-Arg-Trp-NH.
AB  - The melanocortin pathway is an important participant in the regulation of skin
      pigmentation, steroidogenesis, obesity, energy homeostasis, and exocrine gland
      function. Melanocortin agonists contain the putative sequence 'His-Phe-Arg-Trp',
      which has been designated as the 'message' sequence for melanocortin peptides,
      and this sequence has been hypothesized to adopt a bioactive reverse turn
      conformation. Exploring the relationship between its structure and biological
      activity, we report the synthesis and evaluation of seven aza-analogs of the
      potent melanocortin receptor agonist Ac-His-D-Phe-Arg-Trp-NH2. Aza-amino acids,
      in which the alpha-carbon was replaced by nitrogen, were inserted along the
      peptide sequence to probe the importance of local configuration and turn
      conformation on the biology of this tetrapeptide. Although systematic
      substitution of aza-amino acids for the D-Phe and Arg residues led to a
      significant loss of activity relative to the parent peptide for all melanocortin
      receptor subtypes examined, substitution of aza-amino acids at the C-terminal Trp
      residue gave analogs equipotent to the parent peptide. In summary, the aza-scan
      has demonstrated that recognition of this tetrapeptide by the melanocortin
      receptors is particularly sensitive to modifications of configuration and
      conformation at the D-Phe and Arg residues versus the Trp amino acid. In light of
      aza-residues imparting resistance from enzymatic degradation, C-terminal aza
      amino acid analogs may be used to design new peptide mimics with enhanced
      metabolic stability.

PMID- 16629826
TI  - A QSAR model of HERG binding using a large, diverse, and internally consistent
      training set.
AB  - Over the past decade, the pharmaceutical industry has begun to address an
      addition to ADME/Tox profiling--the ability of a compound to bind to and inhibit
      the human ether-a-go-go-related gene (hERG)-encoded cardiac potassium channel.
      With the compilation of a large and diverse set of compounds measured in a
      single, consistent hERG channel inhibition assay, we recognized a unique
      opportunity to attempt to construct predictive QSAR models. Early efforts with
      classification models built from this training set were very encouraging. Here,
      we report a systematic evaluation of regression models based on neural network
      ensembles in conjunction with a variety of structure representations and feature
      selection algorithms. The combination of these modeling techniques (neural
      networks to capture non-linear relationships in the data, feature selection to
      prevent over-fitting, and aggregation to minimize model instability) was found to
      produce models with very good internal cross-validation statistics and good
      predictivity on external data.

PMID- 16629827
TI  - DNA-binding by functionalized gold nanoparticles: mechanism and structural
      requirements.
AB  - A family of nanoparticles featuring surfaces of varying hydrophobicity was
      synthesized. The efficiency of DNA-binding was determined, demonstrating in a
      fivefold modulation in binding a 37-mer DNA strand. Nanoparticle-binding causes a
      reversible conformational change in the DNA structure, as demonstrated by
      circular dichroism and fluorescence experiments. Furthermore, the affinity of the
      nanoparticle for the DNA can be regulated by external agents, though stability of
      the complex is observed at relatively high ionic strengths.

PMID- 16629828
TI  - The discovery of tropane-derived CCR5 receptor antagonists.
AB  - The development of compound 1, a piperidine-based CCR5 receptor antagonist with
      Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This
      compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for
      the CCR5 receptor and has broad-spectrum activity against a range of clinically
      relevant HIV isolates. The identification of human ether a-go-go-related gene
      channel inhibition within this series is described and the potential for QTc
      interval prolongation discussed. Furthermore, structure activity relationship
      (SAR) around the piperidine moiety is also described.

PMID- 16629829
TI  - Functional magnetic resonance imaging in conscious animals: a new tool in
      behavioural neuroscience research.

PMID- 16629830
TI  - Reproduction phase-related expression of beta-endorphin-like immunoreactivity in
      the nucleus lateralis tuberis of the female Indian major carp Cirrhinus mrigala:
      correlation with the luteinising hormone cells-ovary axis.
AB  - The present study aimed to determine whether beta-endorphin immunoreactivity (bEP
      ir) in the neurones of the nucleus lateralis tuberis (NLT) is linked to the
      seasonal cycle and shows correlation with the number of luteinising hormone (LH)
      cells in the pituitary gland and ovaries in the teleost, Cirrhinus mrigala.
      Although LH cells were moderately immunostained during the resting phase
      (December to January), the morphological profile suggested increased synthetic
      and secretory activity during the preparatory (February to April) and prespawning
      (May to June) phases. However, LH immunoreactivity was greatly reduced (P <
      0.001) in the spawning (July to August) phase, suggesting massive discharge of
      the hormone; this pool was partly replenished in the postspawning (September to
      November) phase. The ovaries grew rapidly in the preparatory and prespawning
      phases; maximal size was attained during spawning, when ovulation occurred.
      Thereafter, the ovaries regressed. The NLT of C. mrigala is divisible into the
      pars lateralis (NLTl) and medialis (NLTm). During the postspawning and resting
      phases, bEP-ir was readily detectable in the NLTm as well as NLTl neurones.
      However, a steady reduction in the immunoreactivity was observed in the NLTm
      neurones during the preparatory through spawning phases (P < 0.001), suggesting a
      negative correlation with the LH cells-ovary axis. Thus, the inhibitory influence
      of beta-endorphin on the gonadotrophin-releasing hormone (GnRH)-LH axis appears
      to be attenuated during the preparatory through spawning phases. This may be
      necessary for the rapid stimulation of the axis culminating in spawning. Neurones
      of the NLTl also showed a gradual reduction in bEP-ir during the preparatory and
      prespawning phases (P < 0.01) and may therefore play a similar role. However,
      significant augmentation of the immunoreactivity was noticed in these neurones
      during the spawning phase (P < 0.001), the physiological significance of which is
      unknown. Although the present study demonstrated a temporal correlation between
      the beta-endorphin in the NLT, LH cells and the ovary, we suggest that the
      peptide in the NLTl and NLTm may show functional duality during the spawning
      phase.

PMID- 16629831
TI  - Differential effects of acute and chronic social defeat stress on hypothalamic
      pituitary-adrenal axis function and hippocampal serotonin release in mice.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis and
      disturbances in serotonin (5-HT) neurotransmission have been implicated in the
      pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has
      been shown to induce increases in core body temperature and corticosterone,
      indicative of a state of chronic stress in subordinate animals. The present study
      further characterised the HPA axis response to social defeat stress, and also
      examined hippocampal extracellular 5-HT release during the stress. Exposure to an
      acute social defeat elicits increases in plasma adrenocorticotrophic hormone and
      corticosterone levels, peaking at 15 and 30 min, respectively, and enhances
      corticotrophin-releasing factor (CRF) mRNA, but not arginine vasopressin (AVP)
      mRNA within the medial parvocellular division of the hypothalamic paraventricular
      nucleus. A concomitant increase in hippocampal corticosterone and 5-HT levels is
      observed. By contrast, although chronic social defeat is associated with greatly
      elevated corticosterone levels, the predominant drive appears to be via
      parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to
      recover for 9 days after chronic social defeat display an increase in immobility
      in the forced swimming model of depression, indicating that animals previously
      exposed to the homotypic defeat stress are sensitised to the behavioural effects
      of a novel stressor. These results demonstrate that social defeat induces
      prolonged activation of the HPA axis and alterations in 5-HT neurotransmission
      that could be of relevance to some of the pathological abnormalities observed in
      clinical depression.

PMID- 16629832
TI  - Refractoriness to short day lengths augments tonic and gonadotrophin-releasing
      hormone-stimulated lutenising hormone secretion.
AB  - Siberian hamsters (Phodopus sungorus) undergo reproductive involution following
      exposure to short winter day lengths. Following approximately 20 weeks of
      exposure to short day (SD) lengths, hamsters become refractory to the inhibitory
      effects of SD, and reproductive competence is restored in anticipation of spring.
      The extent to which changes in gonadal steroid-dependent and -independent
      regulation of gonadotrophin secretion participate in this vernal reactivation of
      the gonads is not known. This experiment tested whether tonic and gonadotrophin
      releasing hormone (GnRH)-stimulated regulation of lutenising hormone (LH)
      secretion differs between photoresponsive and photorefractory Siberian hamsters.
      Male hamsters born into long day (LD) lengths were castrated or subjected to a
      sham-castration surgery at 17 days of age, implanted s.c. with blank or
      testosterone-filled capsules, and housed in LD or SD thereafter. Baseline LH and
      LH responses to GnRH (200 ng/kg, s.c) were measured at 14 (photoresponsive) and
      40 (photorefractory) weeks of age. Despite lower circulating testosterone
      concentrations in gonadally regressed SD hamsters on week 14, tonic LH
      concentrations were comparable among all groups of gonad-intact hamsters on weeks
      14 and 40; however, week 14 SD hamsters exhibited significantly higher GnRH
      stimulated LH responses. Tonic LH concentrations were indistinguishable among all
      groups of castrated hamsters bearing empty implants on week 14, but prolonged
      exposure to LD led to a decrease in resting LH, whereas prolonged exposure to SD
      resulted in an increase in LH. In castrated hamsters bearing testosterone
      implants, baseline LH concentrations were comparable in all groups, but GnRH
      treatment resulted in significantly higher LH concentrations in photorefractory
      (week 40, SD) hamsters relative to all other groups. The data suggest that the
      development of photorefractoriness in Siberian hamsters is characterised by
      enhanced gonadal hormone-independent stimulation of LH secretion, and diminished
      sensitivity to inhibitory negative-feedback effects of testosterone on LH
      secretion. Decreases in responsiveness of gonadotrophin secretion to gonadal
      hormone negative feedback may contribute to the process of photorefractoriness
      and assist in maintaining the growth of reproductive organs during the process of
      gonadal recrudescence.

PMID- 16629833
TI  - Administration of kisspeptin-54 into discrete regions of the hypothalamus
      potently increases plasma luteinising hormone and testosterone in male adult
      rats.
AB  - Kisspeptin-54 is the peptide product of the KiSS-1 gene and an endogenous agonist
      of the GPR54 receptor. KiSS-1 was initially discovered as a metastasis suppressor
      gene, but recent studies demonstrate that the kisspeptin/GPR54 system is a key
      regulator of the reproductive system. Disrupted GPR54 signalling causes
      hypogonadotrophic hypogonadism in rodents and man. Intracerebroventricular or
      peripheral administration of kisspeptin potently stimulates the hypothalamic
      pituitary-gonadal (HPG) axis via the hypothalamic gonadotrophin-releasing hormone
      system. We have investigated the effect of injection of kisspeptin-54 into
      discrete hypothalamic regions on the HPG axis. To construct a dose-response curve
      for the effects of intrahypothalamic kisspeptin administration, adult male Wistar
      rats were cannulated into the medial preoptic area (MPOA) at the level of the
      organum vasculosum laminae terminalis (OVLT). Kisspeptin-54 was injected into the
      MPOA at doses of 0.01, 0.1, 1, 10 and 100 pmol. At 60 min following injection of
      1, 10 or 100 pmol kisspeptin-54, plasma luteinising hormone (LH) and total
      testosterone levels were significantly increased. Adult male Wistar rats were
      then cannulated into the rostral preoptic area at the level of the OVLT (RPOA),
      the MPOA, the paraventricular (PVN), dorsomedial (DMN) and arcuate hypothalamic
      nuclei, and the lateral hypothalamic area. A dose of 1 pmol kisspeptin-54 was
      administered into all areas. The circulating levels of LH and total testosterone
      were significantly increased 60 min postinjection of kisspeptin-54 into the RPOA,
      MPOA, PVN and arcuate nucleus. Our results suggest that kisspeptin may mediate
      its effects on the HPG axis via these regions of the hypothalamus.

PMID- 16629834
TI  - Epidermal growth factor receptor expression and activation in neuroendocrine
      tumours.
AB  - Epidermal growth factor receptor (EGFR) is expressed in many cancers and is
      associated with poor prognosis. EGFR activation pathways have been well
      characterised using tumour cell lines and are known to involve EGFR activation
      through autophosphorylation. Phosphorylation of downstream signalling molecules,
      such as ERK1/2 (extra-cellular regulated kinase 1 and 2) and PKB/Akt (protein
      kinase B), leads to enhanced tumour cell survival and proliferation. Although
      EGFR expression has been determined in neuroendocrine tumour tissue, its
      activation and subsequent effects on the downstream signalling molecules, ERK1/2
      and Akt, have not been studied. We therefore planned to determine the role of
      EGFR in neuroendocrine tumours (NETs) by determining its pattern of expression
      and activation, and the subsequent activation of downstream signalling molecules
      ERK1/2 and Akt. Paraffin-embedded tumour tissue was available from 98 patients
      with NETs (39 foregut, 42 midgut, four hindgut, five paragangliomas, and four of
      unknown origin). Immunohistochemical evaluation was performed for the expression
      of EGFR, p-EGFR, p-Akt, and p-ERK1/2. Ninety-six percent of tumour samples were
      positive for EGFR expression; 63% were positive for activated EGFR; 76% were
      positive for activated Akt; and 96% were positive for activated ERK1/2.
      Importantly, the histological score for the activation of Akt and ERK1/2
      correlated with the histological score for activated EGFR. These data provide a
      rationale for considering EGFR inhibitors in the treatment of NETs. Additionally,
      direct inhibition of Akt and ERK1/2 may provide further therapeutic options in
      the treatment of NETs in the future.

PMID- 16629835
TI  - Effect of neonatal hypothyroidism on the kinetic properties of Na+, K+ -ATPase
      from rat brain microsomes.
AB  - The effects of neonatal hypothyroidism on the kinetic properties of Na+, K+ 
      ATPase from rat brain microsomes were examined. Neonatal hypothyroidism resulted
      in decreased Na+, K+ -ATPase activity compared to control samples (7.4 +/- 1.48
      and 29.8 +/- 2.30 micromol Pi/h/mg protein, respectively, P < 0.001). Substrate
      kinetics studies with ATP, Na+ and K+ revealed that there were generalised
      decreases in Vmax. For ATP, Na+ and K+, activities resolved into two kinetic
      components in the control group. In hypothyroid animals, the low-affinity
      component for ATP was absent. The opposite pattern (i.e. an absence of the high
      affinity component) was noted for Na+. For K+, although both kinetic components
      were discernible in neonatal hypothyroid brain microsomes, the Km of the high
      affinity component was significantly higher (P < 0.001) compared to control
      samples. In the control group, the enzyme displayed allosteric behaviour at high
      concentrations of Mg2+; in hypothyroid animals, the pattern was completely
      allosteric. The Na+, K+ -ATPase enzyme from the hypothyroid brain microsomes
      bound two molecules of ATP rather than one, unlike in the control animals. Our
      results thus indicate that neonatal hypothyroidism results in an impairment of
      microsomal Na+, K+ -ATPase activity in the rat brain, together with subtle
      alterations in the kinetic properties of the enzyme.

PMID- 16629836
TI  - Cold stress induces metabolic activation of thyrotrophin-releasing hormone
      synthesising neurones in the magnocellular division of the hypothalamic
      paraventricular nucleus and concomitantly changes ovarian sympathetic activity
      parameters.
AB  - Recent studies suggest thyrotrophin-releasing hormone (TRH) serves as a
      neurotransmitter and thereby provides a functional vegetative connection between
      the brain and the ovary. In the present study, magnocellular neurones of the
      paraventricular nucleus (PVN) in animals subjected to cold exposure were studied
      to determine the hypothalamic origin of the TRH involved in this pathway. In situ
      hybridisation analysis of hypothalamic tissue showed that cold exposure causes a
      two-fold increase in the total number of neurones expressing TRH mRNA in the PVN.
      Immunohistochemical studies showed that TRH peptide is localised to the
      magnocellular PVN and that the number of TRH immunoreactive cells increases two
      fold following 64 h of cold exposure. Double-immunostaining for MAP-2 and TRH
      revealed that TRH peptide is localised in the perikarya of the magnocellular
      neurones. TRH release was measured in vivo from the magnocellular portion of the
      PVN using push-pull perfusion. Although controls exhibited a very low level of
      TRH release, animals subjected to cold showed a pulsatile-like TRH release
      profile with two different patterns of release: (i) low basal level with small
      bursts of TRH release and (ii) a profile with an up to seven-fold increase in TRH
      release compared to controls. The colocalisation of TRH with the specific somato
      dendritic marker MAP-2 in processes of the magnocellular neurones suggested a
      local release of TRH. Additional studies demonstrated a reduction in ovarian
      noradrenaline content after 48 h of cold exposure, a feature indicative of nerve
      activation at the terminal organ. After 64 h of cold exposure, the ovarian
      noradrenaline returned to control values but the noradrenaline content of the
      coeliac ganglia was increased, suggesting a compensatory effect originating in
      the cell bodies of the sympathetic neurones that innervate the ovary. The
      correlation between the local release of TRH from dendrites within the
      magnocellular PVN in conditions of cold and the activation of the sympathetic
      nerves supplying the ovary raises the possibility that TRH contributes to the
      processing regulating sympathetic outflow and may thereby impact on the
      functional activity of the ovary.

PMID- 16629839
TI  - Locally targeted initiatives to recruit and retain nurses in England.
AB  - AIM: The aim of this study is to provide a detailed account of the locally
      targeted strategies to improve staffing levels by senior nurses responsible for
      recruitment and retention in acute trusts in the National Health Service in
      England. BACKGROUND: There is a shortfall in nursing numbers throughout England.
      Some trusts have employed senior nurses with a specific remit to improve
      recruitment and retention, but little has been published about their work or its
      success. METHODS: Data were collected by telephone using semi-structured
      interviews with standard probes. The tape-recorded interview data were
      transcribed verbatim and analysed by content. RESULTS: Of the 156 acute trusts in
      England, 36 employed a senior nurse to deal with recruitment and retention.
      Twenty-nine were interviewed. All were using a range of locally targeted
      initiatives to attract and retain health-care assistants, newly qualified and
      more experienced practitioners. They also worked closely with university staff to
      attract and retain student nurses who would later seek employment locally.
      Different approaches were used to secure the services of different types of
      staff. CONCLUSION: This exploratory study has revealed a wealth of valuable data
      concerning locally targeted recruitment and retention strategies. Further
      research is needed to examine the effectiveness and cost-effectiveness of the
      initiatives described.

PMID- 16629840
TI  - Do we really understand how to retain nurses?
AB  - AIM: To compare views of nurse executives with those of nurses who have left the
      profession on the importance of retention strategies. BACKGROUND: Although much
      has been written about nursing turnover, there continues to be dissonance among
      decision makers as to why nurses leave the profession and what the most crucial
      issues are for retention. METHOD: Factor analysis was undertaken to compare
      responses of nurse executives with those of nurses employed outside of nursing.
      RESULTS: Contract requirements represented the greatest discrepancy, 1.07,
      followed by legal and employer issues, 1.02; worklife/homelife balance, 0.91;
      external values and beliefs about nursing, 0.75; and professional practice, 0.29.
      CONCLUSIONS: A disparity exists between perceptions of nurse executives and those
      of nurses who have left the profession as to which issues are most critical in
      retention. We suggest that nurse executives ensure sufficient organizational
      support for nursing unit managers who are more likely to understand methods of
      retaining nurses at the clinical interface.

PMID- 16629841
TI  - Extrinsic and intrinsic work values: their impact on job satisfaction in nursing.
AB  - AIMS: The aim of this study was to identify the intrinsic and extrinsic work
      values that were perceived by the members of the Queensland Nurses Union (QNU) in
      Queensland, Australia, to influence job satisfaction. BACKGROUND: The current
      shortage of nurses in Australia has been the focus of many recent studies and
      national inquiries. This shortage is experienced internationally in both
      developed and developing nations. Few studies, however, have examined the results
      of surveys from the model of intrinsic and extrinsic work values and their impact
      on job satisfaction. METHODS: Following a pilot study, a questionnaire was posted
      to 2800 assistants-in-nursing, enrolled and Registered Nurses in October 2001,
      who were members of the QNU. The sampling of nurses was undertaken from three
      sectors - public, private and aged care and therefore the results are reported
      separately for these three sectors. A total of 1477 nurses responded to the
      survey, equating to a total overall response rate of 53%. It should be noted that
      the study was limited to members of the QNU, and therefore does not represent
      nurses who are not members of the Union. RESULTS: The results show that intrinsic
      and extrinsic work values do impact upon job satisfaction and therefore intention
      to leave employment. The results also indicate that work stress was high and
      morale was low and decreasing. CONCLUSIONS: The findings of this study give some
      indication of what should be included in a nursing workforce planning strategy,
      the need for which in Australia is 'fundamental and urgent' (Senate Community
      Affairs References Committee 2002, p. xiii). The findings of this study also
      suggest that a 'one size fits all' solution across sectors will not work.

PMID- 16629842
TI  - Evaluation of an open-rota system in a Danish psychiatric hospital: a mechanism
      for improving job satisfaction and work-life balance.
AB  - AIMS: To evaluate the impact of an open-rota scheduling system on the health,
      work-life balance and job satisfaction of nurses working in a psychiatric ward in
      Denmark. BACKGROUND: The effects of shift rotation and scheduling are well known;
      however, little is known about the wider benefits of open-rota systems. Method A
      structured questionnaire was distributed to control and intervention groups
      preintervention and postintervention (20 months). Nurses within the intervention
      group trialed an open-rota system in which nurses designed their own work-rest
      schedules. RESULTS: Nurses in the intervention group reported that they were more
      satisfied with their work hours, less likely to swap their shift when working
      within the open-rota system and reported significant increases in work-life
      balance, job satisfaction, social support and community spirit when compared with
      nurses in the control groups. CONCLUSIONS: The ownership and choice over work
      rest schedules has benefits for nurses, and potentially the hospital.

PMID- 16629843
TI  - A longitudinal study of job stress in the nursing profession: causes and
      consequences.
AB  - AIM AND BACKGROUND: This study examines the influence of changes in work
      conditions on stress outcomes as well as influence of changes in stress outcomes
      on work conditions. As such, it answers questions still open in the literature
      regarding causality of work environmental characteristics and the health of
      nurses. METHOD: A complete, two wave panel design was used with a time interval
      of 3 years. The sample consisted of 381 hospital nurses in different functions,
      working in different wards. RESULTS: Changes in work conditions are predictive of
      the outcomes, especially of job satisfaction and emotional exhaustion. The
      strongest predictors of job satisfaction were social support from supervisor,
      reward and control over work. The strongest predictors of emotional exhaustion
      were work and time pressure and physical demands. Reversed relationships were
      also found for these outcomes. CONCLUSION: The results of this study are
      consistent with transactional models of stress that indicate that stressors and
      stress outcomes mutually influence each other. To prevent nurses from a negative
      spiral, it seems of importance to intervene early in the process.

PMID- 16629844
TI  - Working conditions, psychosocial resources and work stress in nurses and
      physicians in chief managers' positions.
AB  - The study investigated whether psychosocial work conditions, professional
      network, job support, social network and support, sick leave and salary were
      associated with work stress in nurses in chief manager' positions above ward
      level and physicians in clinical director positions. A sample consisting of 205
      nurses and 274 physicians in chief managers' positions at higher structural level
      answered a questionnaire. Odds ratios were used for estimating the bivariate
      association between work stress and psychosocial resources. The result showed
      that both nurse managers (OR 6.8; 95% CI: 3.5-13.5) and clinical directors (OR
      6.7; 95% CI: 3.6-12.5) exposed to high job demands had a significantly higher
      probability of high level of work stress. The results also indicated that the
      available psychosocial resources taken together inside and outside work did not
      balance the experienced work stress in nurse managers and the clinical directors
      who were exposed to high work demands. No relation was found between work stress
      and sick leave and salary.

PMID- 16629845
TI  - Taking a lead on stress: rank and relationship awareness in the NHS.
AB  - Recent legislation from the Health and Safety Executive will have a significant
      impact on the expectations of how an organization manages stress. This paper
      considers the need for more awareness of risk assessment and risk management that
      takes into account the systemic antecedents of stress. It is suggested that
      assessment of organizational stress levels should include qualitative and
      quantitative methods of data collection to analyse the cumulative wear and tear
      on staff that contributes to the experience of workplace stress. This paper
      explores the importance of leadership within organizational hierarchies. Rank and
      status dynamics are identified as a potentially significant source of workplace
      stress. It is proposed that training in rank dynamics and relationship awareness
      are potential mediators in reducing workplace stress. The National Health Service
      could be a leader in establishing organizational well-being through patterns of
      leadership and relationship that tackles the growing epidemic of workplace
      stress.

PMID- 16629846
TI  - Staff satisfaction with work, perceived quality of care and stress in elderly
      care: psychometric assessments and associations.
AB  - AIMS: To evaluate validity and reliability of three questionnaires measuring
      'work satisfaction', 'patient care' and 'staff health' for staff in elderly care
      and to study the relationship between staff members' satisfaction with work and
      perceived stress. BACKGROUND: Increased workload, difficulties in recruiting and
      retaining nurses are reported in elderly care. Valid and reliable instruments
      measuring staffs' perceptions of work are needed. METHODS: A convenience sample
      of 299 staff answered the questionnaires. RESULTS: Factor analysis of 'work
      satisfaction' gave eight factors, 'patient care' four factors and 'staff health'
      two factors, explaining 52.2%, 56.4% and 56.8% of the variance. Internal
      consistency was mostly satisfactory. Multiple regression analysis revealed a
      model that explained 41% of the variance in perceived stress symptoms.
      CONCLUSIONS: There was support for the instruments' validity and reliability.
      Older age, higher scores/satisfaction with workload, cooperation, expectations
      and demands, personal development and lower scores on internal motivation
      contributed to less stress.

PMID- 16629848
TI  - Introduction: Apolipoproteins and guidelines for prevention of cardiovascular
      disease.

PMID- 16629849
TI  - Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels.
AB  - Apolipoproteins AI and B are structural components of lipoprotein particles, and
      also determinants of the metabolic fate of the encapsulated lipid, cholesterol
      and triglyceride. Development of accurate assays for these apolipoproteins has
      opened the way for their use as predictors of coronary heart disease risk.
      Interpretation of AI and apo B levels is best undertaken with background
      knowledge of the metabolic status of an individual, especially the lipolytic
      capacity as reflected in the triglyceride concentration. Those with raised
      triglyceride, in general, not only have an elevated apo B/apo AI ratio, but also
      apo B-containing lipoproteins with a prolonged residence time and hence ample
      opportunity for modification and damage. Assessment of apolipoprotein levels is
      an aid to risk prediction and can be useful in tailoring treatment.

PMID- 16629850
TI  - The rationale for using apoA-I as a clinical marker of cardiovascular risk.
AB  - An inverse relationship between the concentration of high-density lipoprotein
      (HDL) cholesterol and the risk of developing cardiovascular is well established.
      There are several documented functions of HDLs that may contribute to a
      protective role of these lipoproteins. These include the ability of HDLs to
      promote the efflux of cholesterol from macrophages and foam cells in the artery
      wall and to anti-inflammatory/antioxidant properties of these lipoproteins. The
      fact that the main apolipoprotein of HDLs, apoA-I, plays a prominent role in each
      of these functions adds support to the view that apoA-I should be measured as a
      component of the assessment of cardiovascular risk in humans.

PMID- 16629851
TI  - Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I
      ratio to identify the lipoprotein-related risk of vascular disease.
AB  - The objective of this analysis was to demonstrate the frequency and extent of
      error that results from using the TC/HDL C ratio rather than the apoB/apoA-I
      ratio to estimate the lipoprotein-related risk of vascular disease within 94,667
      men and 75,675 women in the Apoprotein-related Mortality Risk (AMORIS) cohort.
      The odds ratio (OR) for the risk of fatal myocardial infarction was determined
      for 1 SD change in the apoB/apoA-I ratio and all the conventional cholesterol
      ratios--TC/HDL C ratio, LDL C/HDL C ratio, non-HDL C/HDL C ratio. In both men and
      women, the apoB/apoA-I ratio was significantly greater than any of the
      cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA-I
      ratio was taken as the most accurate index of the lipoprotein-related risk of
      vascular disease. Using Receiver Operating Characteristic analysis, it was
      demonstrated that the diagnostic accuracy of the apoB/apoA-I ratio was
      significantly greater than any cholesterol ratio in those with an LDL cholesterol
      <3.6 mmol L(-1) compared to those with an LDL cholesterol >3.6 mmol L(-1).
      Indeed, the difference between the apoB/apoA-I OR compared with the TC/HDL C OR
      progressively widened as risk increased. This suggests that the advantage of the
      apoB/apoA-I ratio is greatest in the population at highest risk. The distribution
      of subjects by quintiles showed in both genders that whilst agreement was
      greatest at the extremes, even at these points there was substantial discordance
      between the TC/HDL C and the apoB/apoA-I ratios. Within the middle of the
      distribution, less than 50% of the values were concordant. Finally, when
      comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male
      subjects and overestimated risk in 26.1% of male subjects, whereas in the female
      subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and
      overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios
      rather than the apoB/apoA-I ratio results in frequent and substantial error in
      the estimation of the lipoprotein-related risk of vascular disease.

PMID- 16629852
TI  - Apolipoproteins AI and B as therapeutic targets.
AB  - Currently the apolipoprotein B:AI ratio integrates information about the
      potential for cardiovascular disease (CVD) risk reduction better than any other
      lipid or lipoprotein index. Certainly it could, with benefit, replace serum
      cholesterol and HDL cholesterol in the estimation of CVD risk. Defining the
      therapeutic target of statin therapy in terms of serum apolipoprotein B (apo B)
      rather than LDL cholesterol could also help to optimize statin treatment.
      Deciding whether a therapeutic response is adequate also requires knowledge of
      whether there is persisting hypertriglyceridaemia, because this gives an
      indication of whether small dense LDL is likely to have been satisfactorily
      reduced. Raising low levels of HDL, probably best measured as apo AI, may also
      prove to be an important aim of treatment. This is, however, a more complex issue
      and also depends on the mechanism by which a particular therapy alters HDL levels
      and on whether the capacity of HDL to perform its anti-inflammatory and
      antioxidative functions is restored. A meta-analysis of randomized clinical
      trials of statins in which apo B and apo AI have been reported could provide
      valuable information.

PMID- 16629853
TI  - Genetics of apolipoprotein B and apolipoprotein AI and premature coronary artery
      disease.
AB  - Increased low-density lipoprotein (LDL) and decreased high-density lipoprotein
      cholesterol (HDL-C) predict premature coronary artery disease, as do elevated
      levels of apolipoprotein B or reduced levels of apolipoprotein AI. Probands were
      studied of families with common genetic forms of dyslipidaemia to determine if
      apo B or apo AI define genetic groups and if apo B or apo AI levels relate to
      premature coronary artery disease risk. Elevated apo B was characteristic of
      familial hypercholesterolaemia, familial combined hyperlipidaemia (FCHL), and was
      seen in individuals with elevated Lp(a). Normal apo B levels were seen in
      familial hypertriglyceridaemia and in 'coronary artery disease with low-HDL
      cholesterol'. Apo AI levels tended to be low in FCHL and were decreased in
      'coronary disease with low-HDL cholesterol'. In familial hypertriglyceraemia,
      even though HDL-C levels were low, normal apo AI and apo B levels were seen in
      the absence of premature coronary artery disease. Therefore, in genetic
      dyslipidaemias elevated apo B levels and reduced apo AI levels (or increased apo
      B/AI ratio) differ and predict premature coronary artery disease.

PMID- 16629854
TI  - Associations between apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI
      ratio and coronary heart disease: a literature-based meta-analysis of prospective
      studies.
AB  - OBJECTIVES: To assess associations of circulating levels of apolipoprotein (apo)
      AI, apoB and the apoB/AI ratio (apoB/A) with risk of incident coronary heart
      disease (CHD). DESIGN: Literature-based meta-analysis of prospective studies.
      DATA SOURCES: Prospective studies in essentially general populations that
      reported on associations between apoAI, apoB or apoB/A and first incident CHD
      outcomes. Studies were identified by computer-based searches and by manual
      searches of the relevant literature. RESULTS: Data from 23 relevant studies were
      identified. For apoAI, with 6333 CHD cases in 21 studies, comparison of
      individuals in the bottom third with those in the top third of baseline values
      yielded a combined relative risk of 1.62 (95% confidence interval: 1.43-1.83),
      i.e. an inverse association. For apoB, a combined analysis of 6320 CHD cases from
      19 studies gave a relative risk of 1.99 (1.65-2.39) for a comparison of
      individuals in the top third versus those in the bottom third of baseline values.
      For apoB/A, with 3730 CHD cases from seven studies, a comparison of individuals
      in the top third versus the bottom third of baseline values gave a combined
      relative risk of 1.86 (1.55-2.22). These associations were somewhat stronger
      following correction for within-person variations in apolipoprotein levels. There
      was evidence of heterogeneity amongst the published studies, but it was only
      partly explained by available study-level characteristics. CONCLUSIONS: The
      present quantitative review suggests the existence of moderately strong
      associations between baseline levels of each of apoAI, apoB, and apoB/A and risk
      of CHD. More detailed analysis, perhaps based on individual participant data from
      prospective studies, could help to overcome several limitations in the present
      review and to clarify any relevance of these apolipoproteins to disease
      prediction and aetiology.

PMID- 16629855
TI  - The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a
      target for lipid-lowering therapy--a review of the evidence.
AB  - During the last several years interest has focused on the importance of the lipid
      transporting apolipoproteins--apoB transports all potentially atherogenic very
      low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and LDL
      particles, and apoA-I transports and acts as the major antiatherogenic protein in
      the HDL particles. The evidence for the apoB/apoA-I ratio being a strong, new
      risk factor for cardiovascular (CV) disease and a target for lipid-lowering
      therapy is reviewed. Results from clinical prospective studies and lipid-lowering
      trials in healthy subjects and in patients with different clinical manifestations
      of atherosclerosis are reported. Risk of nonfatal and fatal myocardial infarction
      and stroke, and manifestations of atherosclerosis documented by angiographic,
      ultrasound and other techniques has been related to conventional lipids and
      apolipoproteins (apo). The cholesterol balance determined as the apoB/apoA-I
      ratio has repeatedly been shown to be a better marker than lipids, lipoproteins
      and lipid ratios. The results indicate that the apoB/apoA-I ratio is a simple,
      accurate and new risk factor for CV disease--the lower the apoB/apoA-I ratio, the
      lower is the risk. Guidelines should be developed in order to recognize the
      important clinical risk information embedded in the apoB/apoA-I ratio.

PMID- 16629856
TI  - Respiratory symptoms as predictors of all-cause mortality in an urban community:
      a 30-year follow-up.
AB  - OBJECTIVE: We investigated the relationship between respiratory symptoms and
      mortality from all causes in a large Norwegian population. We also examined
      mortality during separate periods of follow-up. DESIGN: Population-based,
      prospective cohort study. SETTING AND SUBJECTS: A total of 19,998 men and women
      were randomly selected from the general population of Oslo. They received a
      postal respiratory questionnaire. The response rate was 88%. MAIN OUTCOME
      MEASURES: The relationship between 11 respiratory symptoms and 30 years of total
      mortality was investigated separately for men and women by multivariate analyses
      with adjustment for age, smoking habits and occupational exposure to air
      pollution. RESULTS: The relative mortality risk in comparison with asymptomatic
      subjects varied from 1.36 (95% confidence interval 1.25-1.48) for cough symptoms
      to 2.46 (2.13-2.85) for severe dyspnoea amongst men; the corresponding rates
      amongst women were 1.28 (1.16-1.40) and 1.52 (1.31-1.75), respectively. The
      relative risk of mortality in individuals with 1-3, 4-6 and 7 or more symptoms
      was 1.20, 1.60 and 2.53 (P for trend 0.000) in men and 1.14, 1.47 and 1.84 (P for
      trend 0.000) in women. Except for cough, the mortality rates associated with
      respiratory symptoms decreased significantly during follow-up. The positive
      association between respiratory symptoms and mortality was observed in people
      with and without cardiopulmonary diseases. CONCLUSIONS: Respiratory symptoms were
      significant predictors of mortality from all causes over 30 years, decreased
      during follow-up and were still increased after 30 years.

PMID- 16629857
TI  - Lower serum concentration of matrix metalloproteinase-3 in the acute stage of
      myocardial infarction.
AB  - OBJECTIVES: The importance of matrix metalloproteinases (MMPs) in the progression
      and rupture of the atherosclerotic plaque is gaining increasing recognition but
      the mechanisms are not yet fully understood. The aim of this study was to
      investigate the significance of MMP-3 in the acute phase of myocardial infarction
      (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on
      serum MMP-3 concentration. SUBJECTS: One-hundred and sixty-four patients admitted
      with ST-elevation MI and receiving thrombolysis treatment were included in this
      study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months.
      RESULTS: Serum MMP-3 concentration was significantly increased at 3 months when
      compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1)
      [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P <
      0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum
      concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A;
      19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A
      genotype at 3 months (P < 0.001 between all groups). Female patients had lower
      serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1)
      [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months). CONCLUSIONS:
      Serum concentration of MMP-3 is significantly lower in the acute stage of MI than
      during recovery and is significantly influenced by -1612 5A/6A genotype and
      gender. Together with previous findings, these results primarily implicate MMP-3
      in atherosclerosis progression rather than in acute MI.

PMID- 16629858
TI  - Combined hormone replacement therapy improves lipids but may increase leucocytes.

PMID- 16629859
TI  - 5-HT receptors and visceral hypersensitivity - 2B or not 2B, that is the
      question?

PMID- 16629860
TI  - 5-HT2B receptors do not modulate sensitivity to colonic distension in rats with
      acute colorectal hypersensitivity.
AB  - The 5-HT4 receptor agonist tegaserod is an effective prokinetic agent that
      increases gastrointestinal secretion and reduces visceral sensitivity. Tegaserod
      has both 5-HT4 receptor agonist and 5-HT2B receptor antagonist activity, the
      latter being a less potent effect of the drug. In a rat model of colonic
      hypersensitivity, selective 5-HT4 receptor antagonists only partially reversed
      the antihyperalgesic effect of tegaserod suggesting that non-5-HT4 receptor
      mediated mechanisms may also be involved in its overall antihyperalgesic action.
      The objective of this study was to determine whether 5-HT2B receptors play a role
      in colonic hypersensitivity. A visceromotor response (VMR) in acutely sensitized
      animals (intracolonic acetic acid, 0.6%, 1.5 mL) quantified colonic
      hypersensitivity. Acetic acid produced an increase in the VMR at all distension
      pressures. However, neither the 5-HT2B receptor agonist BW 723C86, the 5-HT2B
      antagonist SB204741 or the 5-HT2B/2C antagonist SB 206553 caused any significant
      inhibition of the VMR. In summary, in the same rodent model in which tegaserod
      has previously been shown to produce a potent antihyperalgesic effect, 5-HT2B
      receptors do not appear to mediate colonic hypersensitivity. We conclude that 5
      HT2B receptor-mediated mechanisms are unlikely to play a role in the
      antihyperalgesic action of tegaserod in man.

PMID- 16629861
TI  - Challenges in drug development for functional gastrointestinal disorders. Part I:
      functional dyspepsia.
AB  - There is a need to have predictive biomarkers to test novel experimental
      medicines in functional gastrointestinal disorders (FGID). The human
      pharmacodynamic models and biomarkers in functional dyspepsia (part I) and
      visceral pain (part II) are reviewed, including the general challenges of these
      two disorders (part I). Part II will also discuss the importance of drug
      pharmacokinetics and potential of pharmacogenomics, including the influence of
      CYP metabolism and potential drug interactions. The great heterogeneity of
      mechanisms potentially responsible for dyspeptic symptoms adds a significant
      complexity to this FGID. Strategies are needed to identify subgroups most likely
      to benefit from a specific pharmacological action targeted to one or more
      mechanisms. Thus, while there are significant challenges in drug development for
      functional dyspepsia, there is still an important role for pharmacodynamic
      studies. It remains to be demonstrated that identifying subgroups enhances the
      response to the pharmacological drug effect. This is feasible as the end points
      and performance of each test of gastric emptying, accommodation and sensitivity
      are well characterized. Of these, gastric emptying appears best validated at
      present, though responsiveness to this biomarker has not yet been translated into
      positive phase III trials. Eligibility criteria are proposed for selection of
      patients for functional dyspepsia trials.

PMID- 16629862
TI  - Challenges in drug development for functional gastrointestinal disorders. Part
      II: visceral pain.
AB  - There is a need to have predictive biomarkers to test novel experimental
      medicines in functional gastrointestinal disorders. The human pharmacodynamic
      models and biomarkers pertaining to two important conditions are reviewed in a
      two-part article: functional dyspepsia (part I) and visceral pain (part II). With
      visceral pain models, the large coefficient of variation in sensation end points
      in human studies precludes definitive conclusions such as go/no go decisions or
      dose selection for phase IIb or III studies, unless very large numbers of
      patients are evaluated in phase IIA pharmacodynamic studies. This renders such
      pharmacological studies ambitious, or unachievable in a timely fashion. Moreover,
      the results of tests and clinical trials should be interpreted with greater
      knowledge of the drug pharmacokinetics, including the influence of CYP metabolism
      and potential drug interactions. Thus, it is important to identify valid
      biomarkers of visceral pain for the assessment of treatment response in
      pharmacodynamic studies. In this second part of a two-part article, we shall
      discuss the special challenges in developing medications for visceral pain and
      the general importance of including pharmacokinetic and pharmacogenomic studies
      in drug development programmes.

PMID- 16629863
TI  - Relationship between gastro-oesophageal reflux and gastric activity in newborns
      assessed by combined intraluminal impedance, pH metry and epigastric impedance.
AB  - The pathogenesis of gastro-oesophageal reflux disease (GORD) is complex and
      multifactorial. A motility disorder resulting from immaturity of the gastro
      oesophageal tract may be involved. We have combined multichannel intraluminal
      impedance (MII) and pH monitoring with epigastric impedance (EGI) to evaluate the
      activity of this tract in neonates with suspected GORD. Multichannel intraluminal
      impedance, pH and EGI were followed for 3 h in 30 newborns displaying apparent
      life-threatening events and signs of GORD. Simultaneous application of MII and pH
      monitoring identifies reflux episodes and illustrates their duration, height and
      pH. Episodes detected by MII were placed on the EGI curve and the contemporaneous
      gastric filling state and emptying velocity were calculated. During the total
      measuring time, 248 reflux episodes were revealed. An inverse correlation was
      evident for reflux frequency and gastric emptying velocity (r2 = 0.94; P <
      0.001), and between acid refluxes and the gastric filling state (r2 = 0.95; P <
      0.001), whereas a positive correlation was found between the reflux level and the
      gastric filling state (r2 = 0.52; P < 0.05). Simultaneous MII, pH and EGI
      monitoring provided new information on the relationship between refluxes and
      gastric activity. Data suggest that gastric emptying patterns influence the
      frequency, level and pH of reflux episodes.

PMID- 16629864
TI  - Predictors of gastric emptying in Parkinson's disease.
AB  - Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's
      disease (PD) of a solid and liquid meal are not well defined. For measurement of
      GE 80 patients with PD were randomly assigned to receive either a solid meal (250
      kcal) containing 13C-octanoate (n = 40) or a liquid meal (315 kcal) with 13C
      acetate (n = 40). All patient groups were off medication affecting motility and
      were matched for age, gender, body mass index, disease duration and severity,
      using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was
      compared with a healthy control group (n = 40). Multiple regression analysis was
      used to determine predictors of gastric emptying. Exactly 88% and 38% of PD
      patients had delayed GE of solids and liquids respectively. Solid and liquid
      emptying was similar in women and men. There were no differences in GE in PD
      patients < 65 years of age when compared with patients > or = 65 years. Multiple
      regression analysis showed that motor handicaps such as rigour and action tremor
      are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of
      motor impairment, but not any other neurological symptom, as assessed by UPDRS is
      associated with gastroparesis in PD and solid emptying is more likely to be
      delayed.

PMID- 16629865
TI  - Oesophago-gastric junction opening function: assessment using ultrasound imaging
      and the effects of atropine.
AB  - Relaxation and opening of the oesophago-gastric junction (OGJ) is crucial for
      oesophageal transport. A novel ultrasound technique was used to determine OGJ
      opening, before and after atropine, in 12 normals. An ultrasound probe, a solid
      state pressure transducer and an infusion tube were placed inside a 20-mm
      diameter bag, which was placed across the OGJ. At various bag pressures
      ultrasound transducer was pulled across the bag. Acquired B-mode ultrasound
      images were converted into M-mode image to display the oesophagus, OGJ and
      stomach. At low bag-pressure (< 20 mmHg), the OGJ but not oesophagus and stomach,
      is collapsed around the bag. Increasing bag pressure results in gradual opening
      of the OGJ from distal end. M-mode image identified the narrowest region of OGJ
      and corresponding cross-sectional area (CSA) was measured. Mean bag pressure to
      initial OGJ opening was 18 mmHg. Linear relationship between bag-pressure and OGJ
      CSA was observed. Atropine reduced opening bag pressure and shifted the OGJ
      pressure-CSA curve upward without altering slope, i.e. compliance. Our novel
      ultrasound technique to study the OGJ opening function shows two distinct
      components; firstly, related to the tonic OGJ contraction and secondly, to
      passive or viscoelastic properties of the OGJ.

PMID- 16629866
TI  - Efficacy and efficiency of gastric electrical stimulation with short pulses in
      the treatment of vasopressin-induced emetic responses in dogs.
AB  - The aim of this study was to determine the most effective and efficient anti
      emetic parameters of short-pulse gastric electrical stimulation (GES) in dogs.
      Seven female beagle dogs implanted with four pairs of gastric electrodes were
      studied in eight randomized sessions (saline, vasopressin, and six GES sessions
      with different parameters). Each session consisted of four 20-min recordings of
      gastric slow waves and symptoms. In sessions 1 and 2, saline and vasopressin,
      respectively, were infused during the second 20-min period. The protocol of the
      other six sessions was the same as session 2 except that GES was continuously
      applied. It was found that: (1) vasopressin induced gastric dysrhythmia and
      emetic response (P < 0.01, anova); (2) short-pulse GES with a frequency of 14 or
      40 Hz and pulse width of 0.1 or 0.3 ms, but not 0.6 ms was able to reduce
      symptoms induced by vasopressin; (3) short-pulse GES with a pulse width of 0.3 ms
      was the most effective in preventing vasopressin-induced symptoms; (4) none of
      the tested GES methods improved vasopressin-induced gastric dysrhythmia. We
      conclude that vasopressin induces gastric dysrhythmia and symptoms. Short-pulse
      GES with a pulse width of 0.3 ms and frequency of 14 Hz is most effective and
      efficient in preventing vasopressin-induced emetic responses in dogs.

PMID- 16629867
TI  - Suppression of nNOS expression in rat enteric neurones by the receptor for
      advanced glycation end-products.
AB  - Diabetes mellitus results in a loss of neuronal nitric oxide synthase (nNOS)
      expression in the myenteric plexus but the underlying mechanisms remain unknown.
      We hypothesized that this may be mediated by advanced glycation end-products
      (AGEs), a class of modified protein adducts formed by non-enzymatic glycation
      that interact with the receptor for AGE (RAGE) and which are important in the
      pathogenesis of other diabetic complications. Whole mount preparations of
      longitudinal muscles with adherent myenteric plexus (LM-MPs) from the duodenum of
      adult male rats were exposed to glycated bovines serum albumin (AGE-BSA) or BSA
      for 24 h. Western blotting, immunohistochemistry and real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) for mRNA showed a significant
      reduction in nNOS expression in LM-MPs after exposure to AGE-BSA. NO release, as
      measured by the Griess reaction, was also significantly reduced by AGE-BSA. A
      neutralizing antibody against RAGE attenuated the reduction of nNOS protein
      caused by AGE-BSA. Immunohistochemistry revealed co-localization of RAGE
      expression with Hu, a marker for neuronal cells but not for S-100, a glial
      marker. Advanced glycation end-products reduce nNOS expression in the rat
      myenteric neurones acting via the receptor RAGE. Our results suggest novel
      pathways for disruption of the nitrergic phenotype in diabetes.

PMID- 16629868
TI  - The Giome project.

PMID- 16629870
TI  - Prevalence of overweight, obesity, and associated psychological problems in
      Qatari's female population.
AB  - Dissatisfaction with body weight and the use of unhealthy weight reduction
      practices have been reported among adolescents. It is important to conduct
      rigorous studies using large representative samples of female adolescents to
      assess accurately the frequency of dieting, overweight and eating disorders and
      accompanying attitudes. The aim of the present study was to examine the severity
      of dieting and its association with obesity, body satisfaction and psychological
      problems in female adolescents. A representative sample of 800 girls aged 14-19
      years were approached during the period of October to December 2004, and 566
      girls gave consent and participated in the study, thus giving a response rate of
      70.8%. Self-reports were obtained from 566 teenage girls using the Adolescent
      Dieting Scale and the Self-Reporting Questionnaire (SRQ-20) for psychopathology.
      Subjects were classified into three categories: acceptable weight (BMI < 25 kg m(
      2)); overweight (BMI 25-29.9 kg m(-2)); and obese (BMI > 30 kg m(-2)). The
      prevalence of overweight and obesity for female adolescents were 13.4% vs. 1.8%;
      39.9% were intermediate dieters, and 8.3% were extreme dieters. Dieting was not
      associated with age but was significantly associated with body mass index (BMI)
      (P = 0.045). Extreme dieting was strongly associated with peer perception of
      respondent's figure (P < 0.001) and self-perception of figure (P = 0.016).
      Additionally, in adult Qatari population overweight and obesity for males were
      (34.4% vs. 34.6%) and for females were (33.0% vs. 45.3%). This is significantly
      higher than adolescent girls. (P < 0.01). The SRQ score was significantly highest
      in the extreme dieters group (P = 0.005). The extreme dieters get most of their
      education about dieting from school (14.0%) and TV (43.6%). The present study
      revealed strong evidence for the association between frequent dieting and
      overweight, body image dissatisfaction and psychological problems among
      adolescent females.

PMID- 16629871
TI  - Prevalence of obesity in Kuwait and its relation to sociocultural variables.
AB  - This study ascertains the prevalence of obesity and its relationship with some
      sociocultural characteristics in Kuwaiti society. The sample involved 212 men and
      212 women, most of whom are overweight and obese. Grades 1 (body mass index [BMI]
      > 25-30 kg m(-2)), 2 (BMI > 30-40) and 3 (BMI > 40) of obesity characterize 71.2%
      of the sample. Most individuals are in grade 2 obesity, 37.2%. Grade 1 obesity is
      seen in 31.4% of the sample. Obesity increases with age, especially in women. The
      heaviest women are aged 60 years or older (mean BMI of 33.8), about the same mean
      as in the 50-59-year-old age group. The highest frequency of grades 1 and 2
      obesity occur in women 30-39 years old. Fifty per cent of the underweight women
      are 20-29 years old or are over 60 years old. Most women of normal weight are 20
      29 years old. For the men, 60% of the underweight sample are 50-60 years old.
      Male respondents between 30 and 39 years old are the heaviest; 42.7% of the
      sample are within grade 1 obesity and 40.7% of the sample within grade 2 obesity.
      The smallest percentage of men in grades 1 and 2 obesity are those 50-59 years
      old. An association was found between some sociocultural variables and obesity.
      Data show an increasing prevalence of obesity in Kuwait compared with some
      previous studies.

PMID- 16629872
TI  - Diagnosis and management of hypertension in obesity.
AB  - Cardiovascular risk in a patient with obesity hypertension increases with the
      extent of risk factor clustering. It is therefore important to determine the
      global risk of a patient with hypertension rather than to focus solely on blood
      pressure. Every hypertensive should be screened for other than blood pressure
      risk factors, target organ damage and concomitant diseases or accompanying
      clinical conditions. Assessment of blood pressure and target organ damage might
      be more difficult in obese hypertensives than in normal-weight patients.
      Intensive lifestyle interventions can reduce weight, and decrease blood pressure
      and cardiovascular risk in obese hypertensive patients. Current guidelines do not
      provide specific recommendation for pharmacological management of the
      hypertensive patients with obesity. Recent trials have consistently shown that
      therapy involving beta-blockers and diuretics may induce more new-onset diabetes
      compared with other combination therapies. Several lines of evidence suggest that
      anti-hypertensive agents that block the renin-angiotensin system may be
      especially beneficial in treating obese hypertensive patients. Hypertension
      management in obese individuals is complicated by poorer response to treatment,
      and the increased need for multiple medications. It is important to consider
      obstructive sleep apnoea in the differential diagnosis of hypertensive patients
      who respond poorly to combination therapy with anti-hypertensive medications.

PMID- 16629873
TI  - Gut peptides and the regulation of appetite.
AB  - There is a growing worldwide epidemic of obesity. Obese people have a higher
      incidence of type 2 diabetes and cardiovascular disease, and hence present
      increasing social, financial and health burdens. Weight loss is always difficult
      to achieve through lifestyle changes alone, and currently licensed anti-obesity
      drug treatments, such as orlistat and sibutramine, if tolerated, only achieve
      modest weight loss. Therefore, there is a need to identify more potent
      pharmacological targets. In the last 10 years, discoveries of new hormones such
      as leptin and ghrelin, together with greater understanding of previously
      described hormones such as cholecystokinin (CCK), pancreatic polypeptide (PP),
      peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), have led to a rapid
      increase in our knowledge of the regulation of energy balance. Among the most
      important factors, controlling appetite and satiety are peptide hormones released
      from the gut. In this paper, we provide a full up-to-date overview of the current
      state of knowledge of this field, together with the potential of these peptides
      as drugs, or as other therapeutic targets, in the treatment of obesity. Finally,
      we propose an integrated model to describe the complex interplay of these
      hormones in the broader physiology of energy balance.

PMID- 16629874
TI  - The influence of physical activity on abdominal fat: a systematic review of the
      literature.
AB  - The relationship between excess abdominal adipose tissue, metabolic and
      cardiovascular health risk has stimulated interest in the efficacy of physical
      activity in specifically perturbing this adipose depot. The evolution of imaging
      techniques has enabled more direct measurement of changes in abdominal and
      visceral fat. The purpose of this summary was to systematically review the
      relationship between physical activity and abdominal fat. METHODS: Database
      searches were performed on MEDLINE, CINAHL, SPORT DISCUS and PUBMED, from 1985 to
      2005 with keywords "exercise", "abdominal fat" and "visceral fat". RESULTS:
      Nineteen randomized controlled trials (RCTs) and eight non-randomized controlled
      trials were selected. In RCTs using imaging techniques to measure change in
      abdominal fat in overweight or obese subjects, seven out of 10 studies (including
      three trials with type 2 diabetics) reported significant reductions compared with
      controls. Reductions in visceral and total abdominal fat may occur in the absence
      of changes in body mass and waist circumference. Waist-to-hip ratio is not a
      sensitive measure of change in regional adiposity in exercise studies. No studies
      fulfil the Consolidated Standards of Reporting Trials (CONSORT) statement's
      criteria for the highest quality of randomized trial; however, many studies were
      in progress or published before the opportunity to comply with these
      recommendations. Therefore, limited evidence from a number of studies suggests a
      beneficial influence of physical activity on reduction in abdominal and visceral
      fat in overweight and obese subjects when imaging techniques are used to quantify
      changes in abdominal adiposity. More rigorous studies are needed to confirm these
      observations.

PMID- 16629875
TI  - Parental obesity and overweight affect the body-fat accumulation in the
      offspring: the possible effect of a high-fat diet through epigenetic inheritance.
AB  - The prevalence of obesity in adults has been rising continually, as has the
      prevalence of childhood obesity, and a large number of epidemiological studies
      have demonstrated a direct relationship between parental obesity and childhood
      obesity. In this paper, we review the effect of diet, the intrauterine
      environment, and the genetic inheritance on obesity. We described a study in
      detail that used experimental animals as a model to investigate the effect of a
      parental high-fat diet on body-fat accumulation in their offspring. Fertilized
      eggs were transplanted in that study, and body-fat accumulation in the offspring
      of the parents fed a high-fat diet was found to be greater than in the offspring
      of the parents fed a low-fat diet, even when the experimental conditions were the
      same in the intrauterine and subsequent environment. The results suggested that a
      parental high-fat diet before intrauterine developmental stage may increase body
      fat accumulation in the offspring. We discuss the possibility that parental diet
      may influence the lifelong health of offspring and epigenetic inheritance may be
      occurred.

PMID- 16629876
TI  - The impact of childhood obesity on musculoskeletal form.
AB  - Despite the greater prevalence of musculoskeletal disorders in obese adults, the
      consequences of childhood obesity on the development and function of the
      musculoskeletal system have received comparatively little attention within the
      literature. Of the limited number of studies performed to date, the majority have
      focused on the impact of childhood obesity on skeletal structure and alignment,
      and to a lesser extent its influence on clinical tests of motor performance
      including muscular strength, balance and locomotion. Although collectively these
      studies imply that the functional and structural limitations imposed by obesity
      may result in aberrant lower limb mechanics and the potential for musculoskeletal
      injury, empirical verification is currently lacking. The delineation of the
      effects of childhood obesity on musculoskeletal structure in terms of mass,
      adiposity, anthropometry, metabolic effects and physical inactivity, or their
      combination, has not been established. More specifically, there is a lack of
      research regarding the effect of childhood obesity on the properties of
      connective tissue structures, such as tendons and ligaments. Given the global
      increase in childhood obesity, there is a need to ascertain the consequences of
      persistent obesity on musculoskeletal structure and function. A better
      understanding of the implications of childhood obesity on the development and
      function of the musculoskeletal system would assist in the provision of more
      meaningful support in the prevention, treatment and management of the
      musculoskeletal consequences of the condition.

PMID- 16629877
TI  - Glycaemic index effects on fuel partitioning in humans.
AB  - The purpose of this review was to examine the role of glycaemic index in fuel
      partitioning and body composition with emphasis on fat oxidation/storage in
      humans. This relationship is based on the hypothesis postulating that a higher
      serum glucose and insulin response induced by high-glycaemic carbohydrates
      promotes lower fat oxidation and higher fat storage in comparison with low
      glycaemic carbohydrates. Thus, high-glycaemic index meals could contribute to the
      maintenance of excess weight in obese individuals and/or predispose obesity-prone
      subjects to weight gain. Several studies comparing the effects of meals with
      contrasting glycaemic carbohydrates for hours, days or weeks have failed to
      demonstrate any differential effect on fuel partitioning when either substrate
      oxidation or body composition measurements were performed. Apparently, the
      glycaemic index-induced serum insulin differences are not sufficient in magnitude
      and/or duration to modify fuel oxidation.

PMID- 16629878
TI  - John Harvey Kellogg (1852-1943): "Masturbation results in general debility,
      unnatural pale eyes and forehead acne".

PMID- 16629880
TI  - Mechanisms of oral somatosensory and motor functions and their clinical
      correlates.
AB  - This article provides a review of somatosensory and motor pathways and processes
      involved in oral sensorimotor function and dysfunction. It reviews somatosensory
      processes in peripheral tissues, brainstem and higher brain centres such as
      thalamus and cerebral cortex, with a particular emphasis on nociceptive
      mechanisms. It also outlines some of the circuits and processes involved in
      reflexes and motor control. In addition, it emphasizes the concept of
      neuroplasticity and its applicability to oro-facial pain, to motor control and
      motor learning, and to adaptation to changes in the oral sensory environment such
      as may occur with the placement of dental implants.

PMID- 16629881
TI  - Sensory-motor function of human periodontal mechanoreceptors.
AB  - Natural teeth are equipped with periodontal mechanoreceptors that signal
      information about tooth loads. In the present review, the basic force-encoding
      properties of human periodontal receptors will be presented along with a
      discussion about their likely functional role in the control of human
      mastication. Microneurographic recordings from single nerve fibres reveal that
      human periodontal receptors adapt slowly to maintained tooth loads. Most
      receptors are broadly tuned to the direction of force application, and about half
      respond to forces applied to more than one tooth. Populations of periodontal
      receptors, nevertheless, reliably encode information about both the teeth
      stimulated, and the direction of forces applied to the individual teeth.
      Information about the magnitude of tooth loads is made available in the mean
      firing rate response of periodontal receptors. Most receptors exhibit a markedly
      curved relationship between discharge rate and force amplitude, featuring the
      highest sensitivity to changes in tooth load at very low force levels (below 1 N
      for anterior teeth and 4 N for posterior teeth). Thus, periodontal receptors
      efficiently encode tooth load when subjects contact and gently manipulate food
      using the teeth. It is demonstrated that signals from periodontal receptors are
      used in the fine motor control of the jaw and it is clear from studies of various
      patient groups (e.g. patients with dental implants) that important sensory-motor
      functions are lost or impaired when these receptors are removed during the
      extraction of teeth.

PMID- 16629882
TI  - Jaw motor inputs originating from osseointegrated oral implants.
AB  - Jaw motor inputs from endosseous oral implants have been investigated to a
      limited extent. Observations of jaw muscle reflexes in edentulous patients
      rehabilitated by means of implants do not prove that they originate from the
      implants unless the stimuli are properly defined. Few studies have isolated
      inputs, such as electrical of mechanical stimuli, to make sure that they are
      conveyed through the implants. Even under these conditions one should be aware
      that such stimuli can trigger distant receptors. The most striking difference is
      that tapping an upper jaw implant in a fully edentulous patient does not give
      lead to a silent period in the jaw closing muscles. At the clinical level the
      changes in neuromuscular reflexes do not lead to significant problems.

PMID- 16629883
TI  - From osseoperception to implant-mediated sensory-motor interactions and related
      clinical implications.
AB  - Osseointegration of implants in the jaw bone has been studied thoroughly, dealing
      with various aspects such as bone apposition, bone quality, microbiology,
      biomechanics, aesthetics, etc. A key issue that has received much less attention
      is the physiologic integration of the implant(s) and the associated prosthesis in
      the body. The latter aspect is however very important to obtain new insights in
      oral functioning with implant-supported prostheses. Amputated patients
      rehabilitated with a lower limb prosthesis anchored to the bone by means of an
      osseointegrated implant, have reported that they could recognize the type of soil
      they were walking on. Clinical observations on patients with oral implants, have
      confirmed a special sensory perception skill. The underlying mechanism of this so
      called 'osseoperception' phenomenon remains a matter of debate, because
      extraction of teeth involves elimination of the extremely sensitive periodontal
      ligaments while functional reinnervation around implants is still uncertain.
      Histological, neurophysiological and psychophysical evidence of osseoperception
      have been collected, making the assumption more likely that a proper peripheral
      feedback pathway can be restored when using osseointegrated implants. This
      implant-mediated sensory-motor control may have important clinical implications,
      because a more natural functioning with implant-supported prostheses can be
      attempted. It may open doors for global integration in the human body.

PMID- 16629884
TI  - Bruxism: its multiple causes and its effects on dental implants - an updated
      review.
AB  - There is a growing interest in bruxism, as evidenced by the rapidly increasing
      number of papers about this subject during the past 5 years. The aim of the
      present review was to provide an update of two previous reviews from our
      department (one about the aetiology of bruxism and the other about the possible
      role of this movement disorder in the failure of dental implants) and to describe
      the details of the literature search strategies used, thus enabling the readers
      to judge the completeness of the review. Most studies that were published about
      the etiology during the past 5 years corroborate the previously drawn
      conclusions. Similarly, the update of the review about the possible causal
      relationship between bruxism and implant failure reveals no new points of view.
      Thus, there is no reason to assume otherwise than that bruxism is mainly
      regulated centrally, not peripherally, and that there is still insufficient
      evidence to support or refute a causal relationship between bruxism and implant
      failure. This illustrates that there is a vast need for well-designed studies to
      study both the aetiology of bruxism and its purported relationship with implant
      failure.

PMID- 16629885
TI  - Measuring chewing ability in randomized controlled trials with edentulous
      populations wearing implant prostheses.
AB  - In this article, the authors review methods commonly used to measure the
      masticatory ability of patients wearing conventional and implant prostheses.
      Measurement approaches are viewed in two broad categories: laboratory based and
      patient based. The laboratory based measures discussed are mastication time,
      particle size, force measurements, patterns of jaw movement and electromyographic
      (EMG) bursts and total EMG activity. Patient based measures include satisfaction
      and chewing difficulty. Oral health-related quality of life measures and
      diet/nutrition variables are briefly mentioned. Patient-based outcomes are
      recommended as the most appropriate variables of masticatory efficiency.

PMID- 16629886
TI  - A functional perspective on oral implants - state-of-the-science and future
      recommendations.

PMID- 16629887
TI  - Implant-retained overdenture following hemiglossectomy: a 10-year clinical case
      report.
AB  - A clinical evaluation of an implant-supported overdenture placed in the
      edentulous mandible after hemiglossectomy is described. The deltopectoral flap
      covering the mandibular ridge was replaced with a free mucosal graft. Four
      Branemark system implants were inserted into the anterior part of the mandible,
      but one of the four fixtures did not show osseointegration. The superstructure
      was designed as a spaced round bar-attachment supported by three implants so as
      to retain the complete overdenture. In addition to the metal clip, a silicone
      based soft denture liner material was applied in the female portion of the
      attachment so as to prevent the attachment from making a clattering noise upon
      mastication. Although the overdenture required adjustment at regular intervals,
      the treatment was successful both aesthetically and functionally for up to at
      least 10 years.

PMID- 16629888
TI  - A comparison of oral health related quality of life between complete and partial
      removable denture-wearing older adults in Korea.
AB  - The purpose of this study was to compare the oral health related quality of life
      (OHRQoL) between older Korean adults with complete and partial removable dentures
      using oral health impact profile (OHIP). A pool of 4250 Korean older adults was
      identified by random stratification by area from the sample cohort of Korean
      National Survey of Oral Health in the year of 2000. Out of the potential pool,
      445 subjects with removable partial dentures (RPDs) or complete dentures (CDs)
      agreed to be interviewed by telephone. Each question in the survey was about how
      frequently each event was experienced during the past 12 months. To analyse the
      association between OHIP scores and removable denture status, bivariable analysis
      and multiple linear regression analysis were used. RPD users showed higher scores
      on eight items than CD users. They were 'breath stale', 'food catching',
      'sensitive teeth', 'toothache', 'tense', 'unable to brush teeth', 'less tolerant
      to family members' and 'irritable with others'. RPD users might be associated
      with higher scores of functional limitation, physical pain and psychological
      discomfort than CD users. RPD users had slight tendency to be associated with
      higher OHIP-49 score than CD users, but it was not statistically significant. The
      findings of the present study confirm that there is no general OHRQoL difference
      between RPD and CD users. But in the items and subscales of OHIP, RPD users might
      experience more impaired OHRQoL than CD users.

PMID- 16629889
TI  - Quality of life and masticatory function in denture wearers.
AB  - Successful prosthodontic treatments for a patient with removable partial dentures
      including maxillofacial prostheses hopefully brings about psychological wellbeing
      as well as improved health. The purpose of this study was to investigate the
      relationship between quality of life (QOL) and the various aspects of denture
      function. At first, a questionnaire with a visual analog scale with 16 question
      items concerning denture and/or eating problems, the present state of health,
      psychological and physical wellbeing, life satisfaction, and QOL was developed.
      To discuss the validity and reliability of the questionnaire, 48 outpatients who
      wore a denture were asked to fill it out. Next, to discuss the difference in QOL
      of the patient with various kinds of dentures and conditions, 103 outpatients
      were asked to complete the newly developed questionnaire. The questionnaire which
      contained four factor areas with eight questions for denture patients was
      developed by factor analysis with Varimax rotation. The reliability of the QOL
      scale was confirmed by reliability analysis (Cronbach's alpha = 0.784). The QOL
      score of edentulous patients with a complete denture having some trouble chewing
      was significantly lower than that of other denture patients. It was suggested
      that the wearing of a denture significantly affected the QOL of elderly persons.

PMID- 16629890
TI  - Chewing ability and quality of life in an 80-year-old population.
AB  - As quality of life (QOL) could be influenced by oral status in the elderly, we
      examined whether chewing ability or number of teeth affected QOL in 80-year olds.
      A cross-sectional survey included dental examination, chewing self-assessment,
      and a QOL questionnaire. A total of 823 people who were 80 years old participated
      in this study. QOL was assessed in terms of satisfaction with physical condition,
      meals, daily living and social interactions, and with face-scale scores. After
      adjustment for gender, spouse and activities of daily living, dissatisfaction
      with social interactions was 3.9 times more prevalent in individuals able to chew
      four foods or fewer than in those chewing 15. Dissatisfaction with physical
      condition, meals and daily living, and poor face-scale scores, were 2.7, 2.4,
      3.4, and 2.4 times more prevalent, respectively, in subjects chewing four foods
      or fewer. The number of teeth showed little effect. In conclusion, self-assessed
      chewing ability but not number of teeth was associated with QOL in 80-year-old
      subjects.

PMID- 16629891
TI  - Influence of food platform width of mandibular removable partial denture on food
      mixing ability.
AB  - The aim of this study was to clarify the influence of food platform width on food
      mixing ability in patients with mandibular removable partial dentures (RPDs).
      Twelve subjects (six males and six females, mean age 56.8 years) with intact
      dentition except for unilaterally missing mandibular first and second molars
      participated in the study. The food platforms of their RPDs were made of light
      polymerized composite and three platform conditions were evaluated. A food
      platform (Control condition) had 7 mm width with a central focus on the top of
      the residual ridge. Narrowed platforms (5 mm) were created by trimming a lingual
      portion (Buccally oriented occlusion, Buccal condition) or a buccal portion
      (Lingually oriented occlusion, Lingual condition) from the control. Subjects
      chewed a standardized wax cube which provided an estimate of food mixing ability
      [Mixing Ability Index (MAI)] for each of the three platforms. A significant
      effect (P < 0.001) on the MAI was found for food platform type (repeated measures
      one-way analysis of variance). Tukey multiple comparisons found significant
      differences of MAI between Control condition (1.05 +/- 0.26) and Buccal condition
      (0.86 +/- 0.23) (P = 0.032), and between Control and Lingual condition (0.54 +/-
      0.37) (P < 0.001). Furthermore, MAI with Lingual condition was significantly
      smaller than that with Buccal condition (P < 0.001). These results suggest that
      reduction in the width of the food platform may impair masticatory function and
      the buccal portion of mandibular food platform of RPD is more critical for food
      mixing than the lingual portion of the platform.

PMID- 16629892
TI  - The influence of occlusion on jaw and neck muscle activity: a surface EMG study
      in healthy young adults.
AB  - The electromyographic (EMG) characteristics of masseter, temporalis and
      sternocleidomastoid (SCM) muscles during maximum voluntary teeth clench were
      assessed in 27 male and 35 female healthy young adults. Subjects were divided
      into two groups: (i) 'complete' Angle Class I (bilateral, symmetric canine and
      molar Class I relationships), and (ii) 'partial' Angle Class I (one to three
      canine/molar Class I relationships, the remaining relationships were Class II or
      Class III). On average, standardized muscular symmetry ranged 80.7-87.9%. During
      maximum voluntary teeth clench, average co-contraction of SCM muscle was 13.7
      23.5% of its maximum contraction. On average, all torque coefficients (potential
      lateral displacing component) were >90%, while all antero-posterior coefficients
      (relative activities of masseter and temporalis muscles) were >85%. The average
      integrated areas of the masseter and temporalis EMG potentials over time ranged
      87.4-106.8 muV/muV s%. Standardized contractile muscular activities did not
      differ between 'complete' and 'partial' Angle Class I, and between sexes (two-way
      analysis of variance). A trend toward a larger intragroup variability in EMG
      indices was observed in the subjects with 'partial' Angle Class I than in those
      with 'complete' Angle Class I (significant difference for the temporalis muscle
      symmetry, P = 0.013, analysis of variance). In conclusion, the presence of a
      complete or partial Angle occlusal Class I did not seem to influence the
      standardized contractile activities of masseter, temporalis and SCM muscles
      during a maximum voluntary clench. Subjects with a 'complete' Angle Class I were
      somewhat a more homogenous group than subjects with 'partial' Angle Class I.

PMID- 16629893
TI  - Is condylar position a predictor for functional signs of TMJ hypermobility?
AB  - Temporomandibular joint (TMJ) hypermobility is noted only when it interferes with
      smooth mandibular movements. These interferences (viz. clicking sounds and jerky
      mandibular movements) result from condylar dislocation in front of the eminence
      at wide mouth opening, or alternatively in front of the articular disc (posterior
      disc displacement). The aim of this study was to test the hypothesis that
      condyles of hypermobile persons are positioned more anterosuperiorly to the crest
      of the eminence during maximum mouth opening than those of persons without TMJ
      hypermobility. Possible posterior disc displacement was also evaluated. Nine
      persons with symptomatic hypermobility and nine control persons free of internal
      derangements were included, their diagnoses being based upon opto-electronic
      movement recordings. Condylar positions during maximum mouth opening were
      analysed on magnetic resonance images with two slightly different methods,
      showing the degree to which the condyles are displaced around the eminence. No
      posterior disc displacements were found in any of the magnetic resonance images.
      After excluding an outlier and using both measurement methods, a small difference
      in condylar position was found between the two groups of subjects. The condyles
      of all hypermobile persons travelled beyond the eminence; however, so were the
      condyles of nearly half of the non-hypermobiles. The large overlap between both
      groups suggests that condylar position alone is not a good predictor for
      symptomatic TMJ hypermobility. It is probably the combination of condylar
      location in front of the eminence with a particular line of action of the
      masticatory muscles, which gives rise to functional signs of hypermobility.

PMID- 16629894
TI  - Effect of enzymatic and NaOCl treatments on acrylic roughness and on biofilm
      accumulation.
AB  - As denture cleansers should be able to reduce biofilm accumulation without
      changing the acrylic resin surface structure, this study evaluated the effect of
      denture cleansers on surface roughness of acrylic resin and on biofilm
      accumulation. It was conducted a crossover study of three phases of 4 days each
      and 13 volunteers wore palatal appliances containing four specimens of acrylic
      resin of known surface roughness which were extra-orally submitted once a day to
      three groups of separated treatments: (i) negative control, (ii) enzymatic
      commercial solution (Ortoform) or (iii) 0.5% sodium hypochlorite (NaOCl). The
      appliances were immersed eight times a day in a 20% sucrose solution to enhance
      biofilm formation. On morning of the fifth day of each phase, the amount of
      biofilm formed on the specimens was estimated by the amount of protein extracted
      with alkali and the surface roughness of the specimens was again measured. New
      palatal appliances with new specimens were worn by the volunteers in the
      following phases, but the treatments were changed. The roughness of the resin
      increased after the treatments (P < 0.05) but the difference among the cleansers
      was not statistically significant (P = 0.85). The lowest amount of biofilm formed
      on acrylic resin specimens was found for the treatment with NaOCl (P < 0.05) but
      the enzymatic product did not differ from the negative control group (P > 0.05).
      The data suggest that the roughness of acrylic resin was not changed by the
      cleansers, but the ability to reduce biofilm accumulation depended on the product
      used.

PMID- 16629895
TI  - Feasibility of using collagen as the base of the antifungal drug, miconazole.
AB  - The feasibility of using collagen as the base of miconazole was investigated. The
      addition of 33% collagen to a miconazole solution did not affect the minimal
      inhibitory concentration (MIC80) of the miconazole solution for Candida albicans.
      When 1 microg mL(-1) of miconazole in 33% collagen solution was plated on resin
      discs and dried to yield a thin membrane, the growth of C. albicans on the resin
      discs was nearly completely inhibited. In addition, we compared the antifungal
      effect of this collagen solution that contained 1 microg mL(-1) miconazole, with
      the antifungal effect of miconazole gel that had been diluted with glycerol (the
      main component of miconazole gel) to yield a final concentration of 1 microg mL(
      1) of miconazole; as a result, we found that the collagen solution containing 1
      microg mL(-1) miconazole had a stronger antifungal effect. In conclusion, our
      results demonstrated that it may be feasible to use collagen as the base of
      miconazole instead of glycerol, and suggest that a collagen-based miconazole
      solution would have a stronger antifungal effect than commercially available
      miconazole gel. Collagen-based miconazole solution may be useful for the
      treatment of Candida-associated denture stomatitis.

PMID- 16629896
TI  - Effect of various implant coatings on biological responses in MG63 using cDNA
      microarray.
AB  - During the process of bone formation, titanium (Ti) surface is an important
      factor in the modulation of osteoblastic function. This study was conducted in
      order to determine the effects of different Ti surfaces on the biological
      responses of a human osteoblast-like cell line (MG63). MG63 cells were cultured
      on smooth (S), sandblasted large-grit and acid etching (SLA), hydroxyapatite
      (HA), hydroxyfluoride (HF), titanium nitrate (TIN), and diamond-like carbon (DLC)
      Ti. The morphology of these cells were assessed by SEM. The cDNAs prepared from
      the total RNAs of the MG63 were hybridized into a human cDNA microarray (1152
      elements). The appearances of the surfaces observed by SEM were different on each
      of the six dental substrate types. The SLA and HA surfaces were determined to be
      rougher than the others. MG63 cells cultured on SLA and HA exhibited cell-matrix
      interactions. In the expression of genes involved in osseointegration, several
      genes, including bone morphogenetic protein, cadherin, integrin, and insulin-like
      growth factors, were upregulated on the different surfaces. Several genes,
      including fibroblast growth factor receptor 4, Bcl 2-related protein, and
      collagen, were downregulated on the different surfaces. The attachment and
      expression of key osteogenic regulatory genes were enhanced by the surface
      roughness of the dental materials used.

PMID- 16629897
TI  - Fracture resistance of single-tooth implant-supported all-ceramic restorations
      after exposure to the artificial mouth.
AB  - The purpose of this in vitro study was to evaluate the fracture resistance of
      single-tooth implant-supported all-ceramic restorations, composed of zirconium
      dioxide all ceramic restorations on different implant abutments, and to identify
      the weakest component of the restorative system. Forty-eight standardized
      maxillary central incisor zirconia crowns (Procera) were fabricated for two test
      groups and one control group (group Al: alumina abutments; group Zr: zirconia
      abutments; control group Ti: titanium abutments). All abutments were placed on
      the implants (Replace) using titanium screws. The crowns were adhesively luted
      using a resin luting agent (Panavia 21) and artificially aged through dynamic
      loading and thermal cycling. Afterwards, all specimens were tested for fracture
      resistance using compressive load on the palatal surfaces of the crowns. Pair
      wise Wilcoxon rank tests were performed to test for differences in fracture
      resistance values with a global significance level of 0.05. All test specimens
      survived aging in the artificial mouth. No screw loosening was recorded. The
      median fracture resistance was 1251, 241 and 457 N for groups Ti, Al and Zr
      respectively. Statistically significant differences were found for the
      comparisons of group Ti with groups Al and Zr (P < 0.00001), and for the
      comparison of group Al with Zr (P < 0.00001). Results of this study showed that
      all tested implant-supported restorations have the potential to withstand
      physiological occlusal forces applied in the anterior region. Because of the low
      fracture resistance values of group Al, the combination of zirconia crowns and
      alumina abutments should carefully be considered before clinical application.

PMID- 16629898
TI  - Colour stability of porcelain repair materials with accelerated ageing.
AB  - The purpose of this study was to measure and compare the colour stability of
      three porcelain repair materials (Charizma, Clearfil and Silux Plus) with an all
      ceramic material following accelerated ageing. Three composites and one ceramic
      control were subjected to accelerated ageing for a period of 300 h. Initial
      specimen colour parameters were determined in the Commission International de
      I'Eclairage Lab (CIELAB) colour order system with a colorimeter. Colour changes
      were calculated before (DeltaE) and after 300 h of accelerated ageing (DeltaE*).
      Colour difference data were subjected to one-way analysis of variance (anova)
      followed by Duncan's test to examine the interaction between material and time
      interval of ageing. There were no significant difference between DeltaL values of
      Porcelain-Charizma and Porcelain-Silux Plus. All mean DeltaL* values were
      negative after 300 h ageing. Porcelain-Silux Plus demonstrated the highest
      DeltaL* of the investigated groups. There were significant differences between
      baseline 300-h aged specimens with respect to Deltaa*, Deltaa for either of the
      investigated materials. For Silux Plus, Deltaa and Deltaa* values were
      significantly higher than the others. Significant differences were observed
      between baseline and 300-h values for Deltab and Deltab*. Deltab and Deltab*
      values were significantly higher for Silux Plus. There were significant
      differences between baseline and 300-h values of colour difference, DeltaE,
      DeltaE*. Highest DeltaE* value was obtained using the microfilled composite,
      Silux Plus. Lowest value of DeltaE was recorded with the hybrid composite,
      Charizma.

PMID- 16629899
TI  - EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded alpha1
      antitrypsin.
AB  - Misfolded glycoproteins are degraded by a mechanism known as ERAD (ER-associated
      degradation) after retrotranslocation out of the endoplasmic reticulum (ER). This
      mechanism plays an important role in ER quality control. We previously reported
      that an ER membrane protein, EDEM, accelerates ERAD of a misfolded alpha1
      antitrypsin variant, null (Hong Kong) (NHK), suggesting that EDEM may function as
      an acceptor of terminally misfolded glycoproteins. In this study, we constructed
      several genetically manipulated cell lines to test this hypothesis. EDEM
      expression did not alter the secretion rate of properly folded molecules and the
      forced retention of wild-type alpha1-antitrypsin in the ER did not cause its
      association with EDEM, suggesting that EDEM may function as a molecular
      chaperone. To examine this possibility, we analyzed the effect of EDEM over
      expression on the structure of NHK, and found that the accumulation of covalent
      NHK dimers was selectively prevented by the over-expression of EDEM. Co
      expression of NHK with two other ER membrane proteins, calnexin and H(+)/K(+)
      ATPase (beta subunit), did not inhibit NHK dimer formation or accelerate NHK
      ERAD. These results indicate that EDEM may maintain the retrotranslocation
      competence of NHK by inhibiting aggregation so that unstable misfolded proteins
      can be accommodated by the dislocon for ERAD.

PMID- 16629900
TI  - Regulation of mitotic function of Chk1 through phosphorylation at novel sites by
      cyclin-dependent kinase 1 (Cdk1).
AB  - Chk1 is phosphorylated at Ser317 and Ser345 by ATR in response to stalled
      replication and genotoxic stresses. This Chk1 activation is thought to play
      critical roles in the prevention of premature mitosis. However, the behavior of
      Chk1 in mitosis remains largely unknown. Here we reported that Chk1 was
      phosphorylated in mitosis. The reduction of this phosphorylation was observed at
      the metaphase-anaphase transition. Two-dimensional phosphopeptide mapping
      revealed that Chk1 phosphorylation sites in vivo were completely overlapped with
      the in vitro sites by cyclin-dependent protein kinase (Cdk) 1 or by p38 MAP
      kinase. Ser286 and Ser301 were identified as novel phosphorylation sites on Chk1.
      Treatment with Cdk inhibitor butyrolactone I induced the reduction of Chk1-S301
      phosphorylation, although treatment with p38-specific inhibitor SB203580 or siRNA
      did not. In addition, ionizing radiation (IR) or ultraviolet (UV) light did not
      induce Chk1 phosphorylation at Ser317 and Ser345 in nocodazole-arrested mitotic
      cells. These observations imply the regulation of mitotic Chk1 function through
      Chk1 phosphorylation at novel sites by Cdk1.

PMID- 16629901
TI  - Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G
      protein-coupled receptor in intact cells.
AB  - RIC-8 was originally found by genetic studies on C. elegans mutants that were
      resistant to inhibitors of acetylcholinesterase and reported to act in vitro as a
      guanine nucleotide exchange factor for G protein alpha subunits. However, the
      physiological role of a mammalian homolog Ric-8A on G protein-coupled receptor
      signaling in intact cells is largely unknown. We isolated Ric-8A using a yeast
      two-hybrid system with Galphaq and examined the role of Ric-8A on Gq-mediated
      signaling. The small interfering RNA of Ric-8A diminished the Gq-coupled receptor
      mediated ERK activation and intracellular calcium mobilization in 293T cells. Ric
      8A was translocated to the cell membrane in response to the Gq-coupled receptor
      stimulation. The expression of the myristoylation sequence-conjugated Ric-8A
      mutant was located in the membranes and shown to enhance the Gq-coupled receptor
      mediated ERK activation. Moreover, this enhancement on ERK activation and the
      guanine nucleotide exchange activity of Ric-8A for Galphaq were inhibited by Gq
      selective inhibitor YM-254890. These results suggested that Ric-8A potentiates Gq
      mediated signal transduction by acting as a novel-type regulator in intact cells.

PMID- 16629902
TI  - Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut.
AB  - The gene promoter of Drosophila proliferating cell nuclear antigen (dPCNA)
      contains several transcriptional regulatory elements, such as upstream regulatory
      element (URE), DNA replication-related element (DRE, 5'-TATCGATA), and E2F
      recognition sites. In the present study, a yeast one-hybrid screen using three
      tandem repeats of DRE in dPCNA promoter as the bait allowed isolation of a cDNA
      encoding Cut, a Drosophila homolog of mammalian CCAAT-displacement protein
      (CDP)/Cux. Electrophoretic mobility shift assays showed that Cut bound to both
      DRE and the sequence 5'-AATCAAAC in URE, with much higher affinity to the former.
      Measurement of dPCNA promoter activity by transient luciferase expression assays
      in Drosophila S2 cells after an RNA interference for Cut or DREF showed DREF
      activates the dPCNA promoter while Cut functions as a repressor. Chromatin
      immunoprecipitation assays in the presence or absence of 20-hydroxyecdysone
      further showed both DREF and Cut proteins to be localized in the genomic region
      containing the dPCNA promoter in S2 cells, especially in the Cut case upon
      induction of differentiation. These results indicate that Cut functions as a
      transcriptional repressor of dPCNA gene by binding to the promoter region in the
      differentiated state, while DREF binds to DRE to promote expression of dPCNA
      during cell proliferation.

PMID- 16629903
TI  - Sub-nuclear localization of Rad51 in response to DNA damage.
AB  - The repair of DNA double-strand breaks involves the accumulation of key
      homologous recombination proteins in nuclear foci at the sites of repair. The
      organization of these foci in relation to non-chromatin nuclear structures is
      poorly understood. To address this question, we examined the distribution of
      several recombination proteins in subcellular fractions following treatment of
      HeLa cells with ionizing radiation and the crosslinking agent mitomycin C. The
      results showed association of Rad51, Rad54, BRCA1 and BRCA2, but not Rad51C, with
      the nuclear matrix fraction in response to double-strand breaks induction. The
      association of Rad51 with the nuclear matrix correlates with the formation of
      Rad51 nuclear foci as a result of DNA damage. Fractionation in situ confirmed
      that Rad51 foci remained firmly immobilized within the chromatin-depleted nuclei.
      Irs1SF cells that are unable to form Rad51 damage-induced nuclear foci did not
      show accumulation of Rad51 in the nuclear matrix. Similarly, no accumulation of
      Rad51 in the nuclear matrix could be observed after treatment of HeLa cells with
      the kinase inhibitor caffeine, which reduces formation of Rad51 foci. The results
      were compared to the distribution of the phosphorylated histone variant, gamma
      H2AX. These data suggest a dynamic association and tethering of recombination
      proteins and surrounding chromatin regions to the nuclear matrix.

PMID- 16629904
TI  - Does mPER2 protein oscillate without its coding mRNA cycling?: post
      transcriptional regulation by cell clock.
AB  - Does the mammalian oscillatory protein mPER2 show the rhythm without its coding
      mRNA cycling? Here we answer this question by inserting a single copy of
      exogenous mPer2 gene to a NIH3T3 fibroblasts cell line, using Flp-In system. We
      generated the stable cell lines which constantly express mRNAs coding either N
      terminal FLAG-tagged full length mPER2 (FLAG-mPER2(full)) or its C-terminal
      deleted form (FLAG-mPER2(1-1068)), which lacks the binding site to mCRY proteins,
      under the control of human EF-1alpha promoter. Although serum shock induced the
      rhythm of endogenous clock machinery in these cell lines, it did not initiate the
      rhythm of exogenously inserted FLAG-mPer2 genes at the mRNA level. In contrast,
      FLAG-mPER2(full) proteins showed the rhythm without their coding mRNA cycling.
      Since cells expressing FLAG-mPER2(1-1068) also showed the rhythm of FLAG-mPER2(1
      1068) proteins, the direct binding of mCRY and mPER2 seems not necessary for this
      protein oscillation. This system clearly demonstrates that the intracellular
      endogenous clock system has an ability to modify the mPer2 gene post
      transcriptionally to make mPER2 proteins oscillate without its coding mRNA
      cycling.

PMID- 16629905
TI  - Vimentin-Ser82 as a memory phosphorylation site in astrocytes.
AB  - In astrocytes, the PGF(2alpha) or ionomycin treatment induces the phosphorylation
      at Ser38 and Ser82 of vimentin, a type III intermediate filament, by
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). We found here that
      vimentin phospho-Ser82 was dephosphorylated much slower than phospho-Ser38.
      Vimentin phospho-Ser38 was dephosphorylated quickly by purified PP1 catalytic
      subunit (PP1c) in vitro, whereas phospho-Ser82 was insensitive to PP1c. Because
      PP1c directly bound to vimentin through a VxF motif (Val83-Asp84-Phe85), the PP1c
      active site appeared to be unable to approach phospho-Ser82, leading to the
      prolongation of the phosphorylation at Ser-82. In astrocytes, PP1calpha was in
      vivo associated with vimentin filaments. The repetitive treatment by ionomycin at
      a short interval resulted in the sustained elevation of Ser82 phosphorylation,
      leading to the marked disassembly of vimentin filaments. Taken together, these
      results suggest that vimentin is a novel member of binding partner of PP1c in
      astrocytes, and vimentin-Ser82 may act as a memory phosphorylation site.

PMID- 16629906
TI  - Structure and function of primitive immunoglobulin superfamily neural cell
      adhesion molecules: a lesson from studies on planarian.
AB  - Precise wiring and proper remodeling of the neural network are essential for its
      normal function. The freshwater planarian is an attractive animal in which to
      study the formation and maintenance of the neural network due to its high
      regenerative capability and developmental plasticity. Although a recent study
      revealed that homologs of netrin and its receptors are required for regeneration
      and maintenance of the planarian central nervous system (CNS), the roles of cell
      adhesion in the formation and maintenance of the planarian neural network remain
      poorly understood. In the present study, we found primitive immunoglobulin
      superfamily cell adhesion molecules (IgCAMs) in a planarian that are homologous
      to vertebrate neural IgCAMs. We identified planarian orthologs of NCAM, L1CAM,
      contactin and DSCAM, and designated them DjCAM, DjLCAM, DjCTCAM and DjDSCAM,
      respectively. We further confirmed that they function as cell adhesion molecules
      using cell aggregation assays. DjCAM and DjDSCAM were found to be differentially
      expressed in the CNS. Functional analyses using RNA interference revealed that
      DjCAM is partly involved in axon formation, and that DjDSCAM plays crucial roles
      in neuronal cell migration, axon outgrowth, fasciculation and projection.

PMID- 16629910
TI  - Coping with breast cancer in newly diagnosed Iranian women.
AB  - AIM: This paper reports a study exploring how Iranian women coped with newly
      diagnosed breast cancer and provides a foundation for cultural-based care.
      BACKGROUND: Although research has indicated that coping strategies are associated
      with adaptation to breast cancer, and despite the number of women with newly
      diagnosed breast cancer increasing each year, there is no information on how
      Iranian women cope with breast cancer when compared with women of other cultures.
      METHOD: In this qualitative study, 19 women with newly diagnosed breast cancer
      were interviewed during the period May-September 2004 about coping with their
      disease. Interviews were analysed using a content analysis method. FINDINGS: The
      main themes emerging from this qualitative study included coping using a
      religious approach (acceptance of disease as God's will; spiritual fighting),
      thinking about the disease (positive thinking: positive suggestion, hope,
      intentional forgetfulness; negative thinking: hopelessness, fear, impaired body
      image), accepting the fact of the disease (active acceptance; passive
      acceptance), social and cultural factors and finally finding support from
      significant others. CONCLUSION: Understanding how Iranian women cope with
      diagnosis of breast cancer is important to nurses involved in the process of
      healing. The majority of strategies used by Iranian women were positive, and
      religious faith played a major role in this. The findings of the study can be
      used to design a nursing approach to improve successful coping in Iranian women
      suffering from breast cancer, and can provide nurses and other healthcare
      professionals with deeper understanding of these women as they face this
      diagnosis.

PMID- 16629912
TI  - Class-3c compression bandaging for venous ulcers: comparison of spiral and figure
      of-eight techniques.
AB  - AIM: This paper reports a study to compare the differences in compression
      produced on a limb using a spiral and a figure-of-eight bandaging technique.
      BACKGROUND: Chronic leg ulcers are a major health problem in Western countries.
      Compression bandaging is the accepted treatment for venous leg ulcers. The spiral
      and the figure-of-eight techniques are traditional methods of applying
      compression bandages. But their performance in terms of pressure profiles is
      unknown. Despite a lack of evidence about technique, class-3c compression
      bandages are not currently recommended for application in a figure-of-eight as
      this is thought to produce dangerously high pressure. METHODS: A cross-over
      experimental design was used with a sample of 26 nurse bandagers. Consistency of
      performance was tested. Bandage stretch and overlap were measured and analysed by
      standard deviation to ensure that the techniques were consistent and repeatable.
      Pressure probes were then applied to the medial, posterior and lateral aspects of
      the lower limb of a healthy volunteer. The class-3c compression bandage was
      applied using both techniques and the pressure profiles around the leg were
      measured under the bandage. The results of each technique were compared using
      independent sample t-tests. The data were collected in 1999. RESULTS: The figure
      of-eight technique provided statistically significantly higher compression at
      lower areas of the leg than the spiral technique. Mean pressure difference was
      20.3 mmHg at the ankle, 22.2 mmHg at the gaiter, 9.4 mmHg at the calf. The
      pressure differences decrease towards the knee with both techniques and decrease
      more steeply with the figure-of-eight technique. CONCLUSION: The spiral technique
      was a safe and comfortable method of bandage application. The figure-of-eight
      also provided graduated compression but with some high areas of pressure, notably
      overlying the Achilles tendon. However, before firm practice recommendations are
      made, replication of the study using a padding layer and a larger sample is
      needed.

PMID- 16629913
TI  - Assessment of need for psychosocial interventions in an Asian population of
      carers of patients with schizophrenia.
AB  - AIM: This paper reports on a study to establish the profile of need for
      psychosocial family interventions and to examine the concurrent validity of the
      Relatives' Cardinal Needs Schedule with an Asian population of carers in England,
      UK. BACKGROUND: Although psychosocial interventions for schizophrenia have a
      strong evidence base, little is known of the needs of Asian families. A cardinal
      need is indicative of the existence of a problem causing the carer a strain for
      which the carer is willing to co-operate if help is offered and for which
      systematic help has not been provided in the last 12 months. METHODS: The
      Relatives' Cardinal Needs Schedule was used to assess needs in a small randomly
      selected sample of Asian carers in one English locality and to compare the
      results with independent measures of patient symptoms and carer distress.
      RESULTS: Feedback from carers indicated that the Relatives' Cardinal Needs
      Schedule was culturally acceptable and appropriate to their needs. There was
      evidence for the validity of the assessment in that there were large and
      statistically significant associations between the number of needs detected by
      the Relatives' Cardinal Needs Schedule and independent measures of both carer
      distress (as measured by the 28 item General Health Questionnaire) and patient
      symptom severity (as reliably assessed from case notes). CONCLUSION: The
      Relatives' Cardinal Needs Schedule may prove useful for nurses and service
      managers in establishing the need for psychosocial family interventions amongst
      Asian families in the United Kingdom.

PMID- 16629914
TI  - Complex intervention development for diabetes self-management.
AB  - AIM: The aim of this paper is to present the development and evaluation of the
      Self-Efficacy Goal Achievement nursing intervention for type 2 diabetes.
      BACKGROUND: Systematic reviews support the clinical effectiveness of diabetes
      self-management programmes that are collaborative, involve biomedical feedback
      and are goal focussed. METHOD: The self-efficacy goal achievement intervention
      comprises patient goal-setting consultations with practice nurses using the
      Diabetes Management Self-Efficacy Scale. The United Kingdom Medical Research
      Council framework for the evaluation of complex interventions by randomized
      controlled trial was used to develop and evaluate the intervention. The
      'preclinical' study included literature analysis and findings from parallel
      studies. The 'phase I' study, carried out in spring 2003, was a small trial of
      the intervention, evaluation of its feasibility, identification of appropriate
      outcome measures for future trials and improvement of the components, with two
      nurses and eight patients. FINDINGS: The 'preclinical' study supported continued
      intervention development. The 'phase I' intervention resulted in a mean reduction
      in participants' glycosylated haemoglobin of 0.93% between baseline and 3-months
      postintervention. It showed an increase in patient self-efficacy and some decline
      in patient diabetes treatment satisfaction. Qualitative data recorded
      therapeutically desirable behavioural changes in all participants. Follow-up
      consultations and goal evaluation were found to be important to patients. Nurses
      reported (i) reservations about the repeated use of components of the
      intervention, which were felt to be repetitive and restrictive; and (ii) the time
      commitment required to deliver the educational sessions. CONCLUSIONS: Most phase
      I components were effective in delivering a feasible nursing intervention. The
      intervention has been adjusted to remove the less effective components and
      enhance the more effective. The outcome measures were appropriate for the
      intervention. A phase II trial is being developed to further test both the
      intervention and research protocol for comparing the intervention to an
      alternative.

PMID- 16629915
TI  - Exploring the experience of weight loss in people with advanced cancer.
AB  - AIM: This paper reports a study of the experience of and concerns about weight
      loss described by patients with advanced cancer, their caregivers and nurse
      specialists. BACKGROUND: Weight loss is reported to be one of the commonest
      symptoms experienced by patients with advanced cancer. There is evidence that it
      can be of concern to patients and their caregivers. However, little is known
      about why this is the case or how people might be helped to live with the
      symptom. METHOD: An exploratory study with a purposive sample of 30 patients, 23
      caregivers, and 14 specialist nurses from the South of England was conducted in
      2003. The in-depth interviews focused on the experience of weight loss and its
      management. Interviews were transcribed verbatim, then analysed using an approach
      informed by Wolcott's framework for qualitative data analysis and Miles and
      Huberman's 'mixed strategy for cross-case analysis'. FINDINGS: Concern was
      experienced when advanced cancer became visible through weight loss. Visible
      weight loss symbolized proximity to death, loss of control and both physical and
      emotional weakness. Despite this, weight loss was not routinely assessed by
      palliative care nurse specialists, who, like others in the patient's social
      network, respected a weight loss taboo in the belief that little could be done to
      help people live with the symptom. CONCLUSION: Weight loss-related concern might
      be mitigated if clinicians adopted a systematic and proactive approach to the
      management of the symptom that breaks through the weight loss taboo.

PMID- 16629916
TI  - Change in perceived psychosocial status following a 12-week Tai Chi exercise
      programme.
AB  - AIM: This paper reports a study to examine change in psychosocial status
      following a 12-week Tai Chi exercise intervention among ethnic Chinese people
      with cardiovascular disease risk factors living in the United States of America.
      BACKGROUND: Regular participation in physical activity is associated with
      protection against cardioavascular disease, and improvements in physical and
      psychological health. Increasing amounts of scientific evidence suggests that
      mind-body exercise, such as Tai Chi, are related to improvements in mental
      health, emotional well-being, and stress reduction. No prior study has examined
      the effect of a Tai Chi exercise intervention on psychosocial status among people
      with cardiovascular disease risk factors. METHODS: This was a quasi-experimental
      study. Participants attended a 60-minute Tai Chi exercise class three times per
      week for 12 weeks. Data were collected at baseline, 6 and 12 weeks following the
      intervention. Psychosocial status was assessed using Chinese versions of Cohen's
      Perceived Stress Scale, Profile of Mood States, Multidimensional Scale of
      Perceived Social Support, and Tai Chi exercise self-efficacy. RESULTS: A total of
      39 participants, on average 66-year-old (+/-8.3), married (85%), Cantonese
      speaking (97%), immigrants participated. The majority were women (69%), with < or
      =12 years education (87%). Statistically significant improvements in all measures
      of psychosocial status were found (P < or = 0.05) following the intervention.
      Improvement in mood state (eta2 = 0.12), and reduction in perceived stress (eta2
      = 0.13) were found. In addition, Tai Chi exercise statistically significantly
      increased self-efficacy to overcome barriers to Tai Chi (eta2 = 0.19), confidence
      to perform Tai Chi (eta2 = 0.27), and perceived social support (eta2 = 0.12).
      CONCLUSIONS: Tai Chi was a culturally appropriate mind-body exercise for these
      older adults, with statistically significant psychosocial benefits observed over
      12-weeks. Further research examining Tai Chi exercise using a randomized clinical
      trial design with an attention-control group may reduce potential confounding
      effects, while exploring potential mechanisms underlying the relaxation response
      associated with mind-body exercise. In addition, future studies with people with
      other chronic illnesses in all ethnic groups are recommended to determine if
      similar benefits can be achieved.

PMID- 16629917
TI  - Concept analysis of perspective-taking: meeting informal caregiver needs for
      communication competence and accurate perception.
AB  - AIM: This paper is a report of an analysis of perspective-taking as presented in
      the nursing and psychological literature between 1972 and 2004. BACKGROUND:
      Little is known about the caregiving processes that drive communication
      competence in patient and informal caregiver relationships. Evidence to date
      suggests that the empathic perspective-taking process plays a key role in
      promoting communication competence, perceptual accuracy and enhanced ability by
      caregivers to meet patients' needs arising in illness. Perspective-taking is a
      concept that has been explored extensively in health or social psychology, but
      not in nursing literature. METHOD: Guided by Morse's typology of attributes and
      rules of relation, the concept of perspective-taking is explored as it is
      presented in nursing and social psychology literature, and in accordance with
      Davis's empathy model. FINDINGS: Extant research and theory suggest that
      perspective-taking is an interpersonal empathic process involving a conscious
      effort in differentiating one's view from the view of another that can bring the
      caregivers' viewpoints in closer alignment with patients' viewpoints. Beginning
      evidence suggests that observers might achieve accurate perceptual accuracy about
      patients' illness experiences if they are prompted to imagine how patients
      perceive the situation and how they feel as a result. Research also needs to
      analyse the characteristics of the patient, informal caregiver and illness
      situation in order to comprehend more fully which caregiver dyads need assistance
      with perspective-taking to optimize their skill in providing sufficient patient
      care. CONCLUSION: The current emphasis for empirical research in caregiving is to
      uncover underlying caregiving processes that exist in pre-existing patient and
      informal caregiver relationships. Once further evidence is found to further
      corroborate the perspective-taking process and perceptual accuracy linkage and
      factors that moderate this linkage, then evidence-based interventions can be
      designed and tested to optimize empathic processes that minimize perceptual
      differences between patients and informal caregivers.

PMID- 16629918
TI  - Dimensional analysis of the concept of obesity.
AB  - AIM: The aim of this paper is to explore the evolution of the concept of obesity
      and to identify variations in its meaning and use from the perspectives of
      healthcare professionals and Black Americans, Caucasian Americans, and Latino
      Americans. BACKGROUND: Obesity constitutes an emerging global healthcare
      epidemic. Little convergence is found between the meaning and use of the concept
      of obesity by healthcare professionals and those they are trying to serve. This
      lack of convergence points to the need for exploration of the assumptions, use
      and various meanings associated with this important concept. METHOD: The analysis
      included 20 papers from 18 research studies from the fields of nursing,
      psychology, epidemiology, medicine, and sociology. Caron and Bowers' dimensional
      analysis method guided the analysis. RESULTS: Eight dimensions were identified:
      objective measure, attractiveness, sexual desirability, health, body image,
      strength or goodness, self-esteem, and social acceptability. Substantial
      differences in assumptions, use, and meanings of this concept were found within
      and between the perspectives studied. However, there were insufficient data to
      fully assess use and meaning of the concept of obesity from the Latino American
      perspective. CONCLUSION: This analysis contributes to the development of an
      understanding of the meaning and use of the concept of obesity within varied
      socio-cultural contexts as well as from a healthcare perspective. Culture was
      found to play a significant role in how obesity is understood by the individual.

PMID- 16629919
TI  - Nursing and midwifery students' approaches to study and learning.
AB  - AIM: This paper reports an investigation of the approaches to study and learning
      of nursing and midwifery students at a school of nursing and midwifery in Iran.
      BACKGROUND: Current knowledge suggests that students approach their studies in
      surface, deep or strategic manners. Students' approaches to study have an
      important impact on their academic success. Awareness of their approaches to
      study and factors that affect their choices is important for curriculum planners
      as well as nurse and midwife educators. METHODS: A cross-sectional design was
      used with a convenience sample of nursing and midwifery students in all 3 years
      of study at one university in Iran. The validated Persian translation of
      Entwistle and Ramsden's Approaches and Study Skills Inventory was administered in
      a classroom context in 2003. RESULTS: Sixty-four per cent (95% CI; 57-72%) of
      nursing and 63% (95%; CI 50-75%) of midwifery students adopted a deep approach.
      The use of a surface approach was negatively correlated to the stage of study for
      midwifery but not nursing students. There was also a statistically significant
      positive correlation between level of interest in the field of study and use of
      strategic approach for both nursing and midwifery students. Grade point average
      for the nursing students adopting the strategic approach was statistically
      significantly higher than for those adopting deep or surface approach. The grade
      point average for midwifery students adopting strategic approach was
      statistically significantly higher than that for those adopting deep approach,
      but not different from the grade point average of those adopting surface
      approach. CONCLUSION: Our findings suggest that adoption of strategic or deep
      approaches to learning was associated with better educational outcome, as
      indicated by higher grade point averages. Moreover, the findings emphasize the
      impact of students' interest in their field on their academic success. Therefore,
      the adoption of factors which foster deep or strategic approaches and activities
      which increase students' interest should lead to improved academic outcomes.

PMID- 16629920
TI  - Effectiveness of intermediate-fidelity simulation training technology in
      undergraduate nursing education.
AB  - AIM: The aim of this paper is to present the results of a study designed to
      determine the effect of scenario-based simulation training on nursing students'
      clinical skills and competence. BACKGROUND: Using full-scale, realistic, medical
      simulation for training healthcare professionals is becoming more and more
      common. Access to this technology is easier than ever before with the opening of
      several simulation centres throughout the world and the availability on the
      market of more sophisticated and affordable patient simulators. However, there is
      little scientific evidence proving that such technology is better than more
      traditional techniques in the education of, for example, undergraduate nursing
      students. METHODS: A pretest/post-test design was employed with volunteer
      undergraduate students (n = 99) from second year Diploma of Higher Education in
      Nursing programme in United Kingdom using a 15-station Objective Structured
      Clinical Examination. Students were randomly allocated to either a control or an
      experimental group. The experimental group, as well as following their normal
      curriculum, were exposed to simulation training. Subsequently, all students were
      re-tested and completed a questionnaire. The data were collected between 2001 and
      2003. RESULTS: The control and experimental groups improved their performance on
      the second Objective Structured Clinical Examination. Mean test scores,
      respectively, increased by 7.18 and 14.18 percentage points. The difference
      between the means was statistically significant (P < 0.001). However, students'
      perceptions of stress and confidence, measured on a 5-point Likert scale, was
      very similar between groups at 2.9 (1, not stressful; 5, very stressful) and 3.5
      (1, very confident; 5, not confident) for the control group, and 3.0 and 3.4 for
      the experimental group. CONCLUSIONS: Intermediate-fidelity simulation is a useful
      training technique. It enables small groups of students to practise in a safe and
      controlled environment how to react adequately in a critical patient care
      situation. This type of training is very valuable to equip students with a
      minimum of technical and non-technical skills before they use them in practice
      settings.

PMID- 16629921
TI  - E-learning for healthcare students: developing the communities of practice
      framework.
AB  - AIM: This paper presents research considering whether healthcare students were
      able to develop characteristics of communities of practice when engaged in an
      online module. BACKGROUND: Little is known about whether the communities of
      practice framework can be applied to online learning, with no previous
      consideration of its potential use within healthcare education. METHODS: Using a
      case study approach the research, completed in 2004, had two phases. A
      questionnaire was administered to a group of 109 healthcare students to gain
      information on which to base sampling for the subsequent phase. Phase 2 employed
      three strands of data collection: five students completed an online diary, the
      online interactions of seven students were captured on a discussion board and
      three students were interviewed. Data were analysed using a form of pattern
      matching. FINDINGS: Students were able to develop essential elements of
      communities of practice: mutual engagement, joint enterprise and shared
      repertoire, though this was not uniformly seen. Particular issues emerged for the
      online community, including enabling access to the online environment to support
      mutual engagement. The development of trust was also threatened by difficulties
      of presenting identities online. Joint enterprise was hampered by the online
      situation, although the virtual classroom proved essential for supporting
      endeavour. Not all students were committed to their groups. There was some
      evidence of group members developing shared repertoire, as routines of group
      working emerged. Professional understanding and computer skills were also
      enhanced. CONCLUSION: The framework can be applied to supporting online learning
      internationally amongst students and has applicability to professional groups.
      Those intending to employ the framework should ensure that students can gain
      access to the community and have the computer skills to engage. Course design
      should be considered to ensure support for developing the essential components of
      communities of practice.

PMID- 16629922
TI  - Health promotion for frail older home care clients.
AB  - AIM: This paper reports a study evaluating the comparative effects and costs of a
      proactive nursing health promotion intervention in addition to usual home care
      for older people compared with usual home care services alone. BACKGROUND: An
      ageing population, budget constraints and technological advances in many
      countries have increased the pressure on home care resources. The result is a
      shift in nursing services from health promotion to meet the more pressing need
      for postacute care. For frail older people with long-term needs, these changes
      combine to create a fragmented system of health service delivery, characterized
      by providing nursing on demand rather than proactively. METHODS: A two-armed,
      single-blind, randomized controlled trial was carried out with older people > or
      =75 years and eligible for personal support services through a home care
      programme in Ontario, Canada. Participants were randomly allocated either to
      usual home care (control) or to a nursing (experimental) group. In addition to
      usual home care, the nursing group received a health assessment combined with
      regular home visits or telephone contacts, health education about management of
      illness, coordination of community services, and use of empowerment strategies to
      enhance independence. The data were collected in 2001-2002. RESULTS: Of the 288
      older people who were randomly allocated at baseline, 242 (84%) completed the
      study (120 nursing group; 122 control group). Proactively providing older people
      with nursing health promotion, compared with providing nursing services on
      demand, resulted in better mental health functioning (P = 0.009), a reduction in
      depression (P = 0.009), and enhanced perceptions of social support (P = 0.009) at
      no additional cost from a societal perspective. CONCLUSIONS: Home based nursing
      health promotion, proactively provided to frail older people with chronic health
      needs, enhances quality of life while not increasing the overall costs of health
      care. The results underscore the need to re-invest in nursing services for health
      promotion for older clients receiving home care.

PMID- 16629925
TI  - Modes of imprinted gene action in learning disability.
AB  - BACKGROUND: It is now widely acknowledged that there may be a genetic
      contribution to learning disability and neuropsychiatric disorders, stemming from
      evidence provided by family, twin and adoption studies, and from explicit
      syndromic conditions. Recently it has been recognized that in some cases the
      presentation of genetic syndromes (or discrete aspects of disorders) is dependent
      on the sex of the transmitting parent. Such 'parent-of-origin effects' can be
      explained by a number of genetic mechanisms, a predominant one of which is
      genomic imprinting. Genomic imprinting refers to the parent of origin-specific
      epigenetic marking of an allele of a gene, such that for some genes it is mainly
      the maternally inherited allele only that is expressed, whereas for others
      expression occurs mainly from the paternal copy. METHODS: Here we discuss the
      contribution of imprinted genes to mental dysfunction and learning disability,
      using clinical examples of association studies and explicit imprinting disorders
      (with particular emphasis to Angelman and Prader-Willi syndromes), and evidence
      from animal work. RESULTS: Clinical and animal studies strongly suggest that
      imprinted genes contribute to brain functioning, and when the genes or epigenetic
      processes are disrupted, this can give rise to neuropsychiatric problems. Another
      system to which imprinted genes provide a large contribute is the placenta and
      foetal development. Epidemiological studies suggest that this is also a key area
      in which dysregulation can give rise to learning difficulties. CONCLUSIONS:
      Disruption of imprinted genes, or the epigenetic processes controlling them, can
      contribute to learning disability. These effects can be divided into two types:
      direct effects, such as those seen in explicit imprinting disorders such as
      Angelman and Prader-Willi syndromes, and indirect effects as manifest via changes
      in foetal programming.

PMID- 16629926
TI  - Living conditions of adults with intellectual disabilities from a gender
      perspective.
AB  - BACKGROUND: The role of gender has been a neglected issue in research on
      intellectual disability (ID). People with ID are generally treated as a
      homogenous group that are largely categorized by their level of ID. This study
      compared living conditions of women and men with ID and related the results to
      similarities and differences among the general population in corresponding age
      groups. METHODS: Persons with ID born in Uppsala County between 1959 and 1974
      constituted the study sample. Information on the living conditions of 110 persons
      with ID was collected using questionnaires completed by relatives and staff.
      Information on living conditions of the general population was obtained through
      national welfare statistics conducted by Statistics Sweden (SCB). RESULTS: In
      both samples corresponding diversities were revealed for type of employment/daily
      activities, where women worked in traditional female job sectors and men were
      occupied with traditional male jobs. Women and men with ID participated to about
      the same extent in recreational and cultural activities and on only four of the
      19 activities listed in the questionnaire (visits to the cinema and library,
      reading books and practising hobbies alone) significant differences were
      observed. Among women and men in the general population, we found gender-related
      differences in 13 of the activities listed. However, with the exception of women
      more frequently visiting the library and reading books, the two samples
      demonstrated no corresponding gender-related differences. For the remaining six
      domains (finances, family and social relations, housing, transport, community
      participation and personal safety), no differences were noted between women and
      men with ID. This finding contrasted sharply with the differences found between
      women and men in the general population. CONCLUSIONS: Surprisingly, the
      comparison yielded few differences in living conditions between women and men
      with ID compared with those found in women and men of the general population.
      This finding suggests that people with ID were treated as gender-neutral persons
      rather than as women and men with individual preferences and needs. Thus, it
      appears that having ID is a more important determinant than gender regarding
      living conditions for women and men with ID.

PMID- 16629927
TI  - A cross-sectional multivariate analysis of children's attitudes towards
      disabilities.
AB  - BACKGROUND: Past research has shown that children can be biased against peers
      with disabilities, but the association of attitudes with gender, age and
      disability preferences, as well as interactions between these variables, are
      unclear. The objectives of this study were to examine these issues in a cross
      sectional, split-plot study to clarify: (1) if elementary school children's
      attitudes towards peers with disabilities are related to age, gender and type of
      disability; (2) if interactions between these variables exist; and (3) if
      convergent validity could be achieved across three theoretically linked dependent
      variables. METHODS: One hundred elementary school children between 4 and 10 years
      old were assessed for attitudes towards target children with no disability, a
      physical or an intellectual disability, and a combined intellectual/physical
      disability. Measures were completed in an interview format. RESULTS: Attitudes
      towards a target child with physical disabilities and a target child without
      disabilities did not differ. There was a significant interaction for age and
      disability. Attitudes towards target children with intellectual and
      intellectual/physical disabilities were negatively biased, and were negatively
      associated with age. Results were consistent across measures except for a main
      effect of gender in one measure and a gender by age interaction in another.
      CONCLUSIONS: Children's attitudes appear to be associated with several factors,
      including age and the presence or absence of disability. Gender differences in
      attitudes may be because of gender-based response biases rather than disability
      biases. Because of the multifaceted nature of childhood attitudes, cross
      sectional designs with several dependent and independent variables provide an
      opportunity to examine consistency of results across measures and potential
      interactions between factors that may not be uncovered when variables are
      examined in isolation.

PMID- 16629928
TI  - The transition to school: adaptation in young children with and without
      intellectual disability.
AB  - BACKGROUND: Previous research has highlighted the importance of the transition to
      school for young children and their families. A child's successful adaptation to
      school is likely influenced by a number of factors, including academic, social,
      emotional, behavioural and cognitive competencies. Children with intellectual
      disability (ID) may be at heightened risk for early school difficulties, in part
      due to their deficits in cognitive and adaptive behaviours. METHODS: Factors
      associated with the adaptive transition to school in young children with (n = 24)
      and without (n = 43) ID were examined. Adaptive transitions were defined as
      having few teacher-reported problem behaviours and positive student-teacher
      relationships. Child self-regulatory skills and both parent- and teacher-reported
      social skills were evaluated to determine if they predicted positive adaptation
      in school for 5- to 6-year-old children. Data were gathered from child
      assessments, parent reports on standardized measures, direct observations of
      delay of gratification tasks and teacher reports on standardized measures.
      RESULTS: Children with ID had significantly more teacher-reported problem
      behaviour, poorer overall student-teacher relationships, fewer parent- and
      teacher-reported social skills and fewer self-regulation skills than typically
      developing children. Self-regulation at child age 36 months (latency to touch a
      desired toy) was significantly related to adaptation to school, as were parent
      and teacher reports of social skills. Social skills significantly predicted
      adaptation to school, even after accounting for the effects of child IQ and
      adaptive behaviour. CONCLUSIONS: Children with ID had less positive early school
      experiences, as indicated by multiple indices of adaptation to school. Fostering
      early social skills may be an important target for increasing the positive
      adaptation to school for young children, especially those with ID.

PMID- 16629929
TI  - Predictors of asphyxiation risk in adults with intellectual disabilities and
      dysphagia.
AB  - BACKGROUND: Adults with learning disabilities referred for assessment of their
      eating and drinking are frequently reported to cough and choke when eating and
      drinking. The research literature investigating dysphagia has often overlooked
      asphyxiation risk, highlighting coughing and choking as indicators of aspiration
      only. This is a notable oversight due to the prevalence of asphyxia as a cause of
      mortality in this population. AIM: This study aims to identify the physiological
      and environmental factors that predict asphyxiation risk in adults with
      intellectual disabilities and dysphagia. METHOD: Data were collected from
      dysphagia-trained speech and language therapists (SLTs) working with the
      participant adults with intellectual disabilities and dysphagia. The SLTs used
      case notes, clinical assessment and videofluoroscopic assessment reports to
      gather the data. RESULTS: Speed of eating, cramming food and premature loss of
      the bolus into the pharynx were identified as significant predictors of
      asphyxiation risk in this population. CONCLUSIONS: The findings highlight the
      importance of maladaptive eating strategies in exacerbating the risk of
      asphyxiation and choking. These factors should be considered in the assessment of
      asphyxiation and choking risk and management. Finally, the need for joint
      assessment and management with other members of the multidisciplinary team is
      advocated.

PMID- 16629930
TI  - Quality of life in adults with an intellectual disability: the Evaluation of
      Quality of Life Instrument.
AB  - BACKGROUND: The construct of quality of life (QoL) has been the focus of a great
      deal of recent research and has been operationalized in the assessment of the
      effectiveness of biomedical and rehabilitative interventions. Consequently, the
      effective measurement of QoL has become a relevant issue. QoL assessment should
      take account of both objective life conditions and reported satisfaction with
      those conditions, and should recognize that QoL has multiple domains. There is
      also evidence to suggest that it is useful to supplement such assessments with
      the evaluations of significant others within a multidimensional assessment
      perspective. METHODS: The current study describes a further stage of testing and
      refinement of the Evaluation of Quality of Life Instrument (EQLI), which was
      designed to elicit from staff of health and social care services assessments of
      the level of satisfaction experienced by adults with an intellectual disability.
      Specifically, the EQLI's internal consistency, and construct, convergent and
      discriminant validity were analysed. RESULTS: The EQLI appears to be a
      psychometrically valid measure for collecting data on the levels of satisfaction
      which, according to health and social services staff, might be experienced by
      individuals with an intellectual disability who attend residential institutions
      and community-based day centres. The factor analyses supported a three-factor
      structure for the EQLI and reliability estimates of scores on the three factors
      were in the moderate to high range. The data collected supported convergent and
      discriminant validity. CONCLUSIONS: The results indicate that the EQLI is an
      effective measure for gaining staff perceptions of individuals who may be at risk
      of dissatisfaction with various QoL domains. The EQLI is as an instrument which,
      within a multidimensional assessment, could contribute to the identification of
      areas of user dissatisfaction with services.

PMID- 16629931
TI  - People with MECP2 mutation-positive Rett disorder who converse.
AB  - BACKGROUND: People with useful speech after regression constitute a distinct
      group of those with mutation-positive Rett disorder, 6% (20/331) reported among
      mutation-positive people in the British Survey. We aimed to determine the
      physical, mental and genetic characteristics of this group and to gain insight
      into their experience of Rett syndrome. METHODS: Clinical and molecular data for
      people with Rett, aged 10 or more years at follow-up (the study group, n = 13),
      with the ability to converse and a MECP2 mutation are presented. They were
      compared with an age-matched control group (n = 110), who could not converse and
      had a pathogenic MECP2 mutation. RESULTS: The study group differed significantly
      from the control group with regard to their disease severity (P < 0.001); feeding
      difficulty scores (P < 0.001); health scores (P < 0.001); epilepsy (P < 0.001);
      head circumference (P < 0.004); age at onset of the regression period (P < 0.001)
      (six in the study group did not regress) and mutation frequency (C-terminal
      deletions P = 0.014, R133C P < 0.006). The results indicate that favourable
      skewing of X-inactivation is only present in a small proportion of mild cases.
      Speech was fragmented with a soft, breathless quality, and all but two had
      obviously irregular breathing. One person with an R168X mutation preferred
      signing to speech. All enjoyed interpersonal contact, showing affection and
      preferring people to objects, clearly distinguishing the condition from autism.
      Most were habitually anxious. Music was a source of pleasure and relaxation also
      providing a valuable educational asset. Even in these most able cases,
      understanding was severely restricted in most and little initiative was shown.
      CONCLUSIONS: While the Rett profile is present in these people they are commonly
      not classic, and the presence of speech, good head growth and lack of regression
      may lead to missed diagnoses. A strong association was demonstrated between this
      milder form of the disease and R133C and C-terminal deletions.

PMID- 16629933
TI  - Review article: the modern diagnosis and therapy of cholangiocarcinoma.
AB  - Cholangiocarcinomas are epithelial neoplasms that originate from cholangiocytes
      and can occur at any level of the biliary tree. They are broadly classified into
      intrahepatic tumours, (extrahepatic) hilar tumours and (extrahepatic) distal bile
      duct tumours. In spite of well-understood predispositions, most
      cholangiocarcinomas arise in the absence of risk factors. In suspected cases, the
      diagnosis can be established with non-invasive imaging studies. Biliary invasion
      should be reserved for patients with obstruction. In high-risk patients, advanced
      cytological tests of aneuploidy (digital image analysis and fluorescent in situ
      hybridization) aid early diagnosis. In the absence of primary sclerosing
      cholangitis, curative surgical resection has 5-year survival rates of 2-43%,
      higher survival observed in patients with clear surgical margins and concomitant
      hepatic resection for hilar tumours. Patients with unresectable
      cholangiocarcinoma or pre-existing primary sclerosing cholangitis should be
      considered for liver transplantation with neoadjuvant chemoirradiation, in
      specialized centres.

PMID- 16629934
TI  - Small intestinal cancer in England & Wales and Scotland: time trends in
      incidence, mortality and survival.
AB  - BACKGROUND: Time trends in mortality from small intestinal cancer have not been
      studied for the 1990s. OBJECTIVE: To examine secular trends in incidence of,
      mortality from, and survival from, small intestinal cancer in England & Wales and
      Scotland from 1975 to 2002, considering also histological type (incidence),
      subsite (incidence) and indices of social deprivation (incidence and survival).
      METHODS: Data were extracted from the Scottish Cancer Registry database and the
      General Register Office for Scotland, and from the National Cancer Intelligence
      Centre at the Office for National Statistics for England & Wales. RESULTS:
      Incidence rates for small intestinal cancer increased for both England & Wales
      and Scotland over the study period. They were highest among older individuals and
      generally greater for males than for females. Despite the increase in incidence
      rates, mortality rates from small intestinal tumours tended to remain stable over
      the study period, and the general trend was towards increasing survival. Indices
      of social deprivation were not obviously related to the incidence of small
      intestinal cancer and did not influence survival. CONCLUSIONS: Incidence rates
      for small intestinal cancer for both England & Wales and Scotland increased in
      the last quarter of the 20th century, but survival rates improved and mortality
      rates declined.

PMID- 16629935
TI  - Barley and rye prolamins induce an mRNA interferon-gamma response in coeliac
      mucosa.
AB  - BACKGROUND: In coeliac disease, wheat, barley and rye are traditionally excluded
      in the gluten-free diet. However, few studies have examined the small intestinal
      immune response to barley and rye. AIM: To investigate the immunogenicity of
      barley and rye prolamins (hordein and secalin respectively) in comparison with
      wheat gliadin. METHODS: Duodenal biopsies from 22 coeliac patients and 23 disease
      controls were cultured for 4 h with gliadin, hordein or secalin and compared with
      culture medium alone. Proinflammatory cytokines, interferon-gamma and interleukin
      2, were quantified by TaqMan polymerase chain reaction and enzyme-linked
      immunosorbent assay. RESULTS: Hordein caused the greatest increase in interferon
      gamma mRNA in coeliac patients (median: 3.3-fold) in comparison with control
      subjects (median: 0.28-fold, P < 0.085). Secalin and gliadin induced similar
      levels of interferon-gamma mRNA with median fold-changes of 3.4 and 2.8,
      respectively, in coeliac patients in comparison with 1.6- and 1.1-fold increases
      in control subjects (P < 0.294 and P < 0.105, respectively). The median fold
      changes for interleukin-2 mRNA did not differ between coeliac patients and
      controls. Cytokine protein was not upregulated. CONCLUSION: The findings of this
      study provide evidence that barley and rye cause immune activation in the mucosa
      of coeliac patients and support the practice that barley and rye should be
      excluded from the gluten-free diet.

PMID- 16629936
TI  - Variability of the 13C-octanoic acid breath test for gastric emptying of solids
      in healthy children.
AB  - AIM: To assess the intra-individual variability of the 13C-octanoic acid breath
      test using non-dispersive infrared spectrometry for gastric emptying of solids in
      healthy children. METHODS: A 13C-octanoic acid breath test was performed at least
      two times in 19 healthy children (age 12.4 +/- 2.7 years) 2-7 days apart to
      measure gastric emptying of solids. Breath samples were taken before eating a 13C
      octanoic acid-labelled pancake and at 15-min intervals for the following 240 min.
      Breath samples were analysed using non-dispersive infrared spectrometry; 13C
      recovery was used to calculate values for gastric half-emptying time (t(1/2)),
      gastric lag phase (t(lag)) and gastric emptying coefficient. Intra-individual
      variability of the parameters t(1/2), t(lag) and gastric emptying coefficient
      were expressed as coefficient of intrasubject variation. RESULTS: The mean
      coefficient of intrasubject variation of t(1/2) was 13.3 +/- 7.9% (range 2.5
      29.6%; interindividual range 99-204 min; intra-individual range 5-84 min for
      t(1/2)). The mean coefficient of intrasubject variation of t(lag) was 13.6 +/-
      7.5% (range 0.8-27.8%) (interindividual range 65-146 min; intra-individual range
      1-50 min for t(lag)). The mean coefficient of intrasubject variation of gastric
      emptying coefficient was 12.5 +/- 6.8% (range 3.4-30.2%; interindividual range
      2.3-3.9; intra-individual range 0.17-1.4 for gastric emptying coefficient). The
      coefficient of intrasubject variations of t(1/2), t(lag) and gastric emptying
      coefficient were independent of the values of t(1/2), t(lag) and gastric emptying
      coefficient. CONCLUSIONS: Gastric emptying in healthy children is characterized
      by a large inter- and intra-individual variability and is concordant with the
      results obtained with other techniques.

PMID- 16629937
TI  - Gastro-oesophageal reflux disease in 'difficult-to-control' asthma: prevalence
      and response to treatment with acid suppressive therapy.
AB  - BACKGROUND: The causal association between gastro-oesophageal reflux disease
      (GERD) and difficult-to-control asthma is unclear. AIM: To determine the
      prevalence of GERD and response to proton pump inhibitor therapy in patients with
      difficult-to-control asthma. METHODS: Consecutive patients with difficult-to
      control asthma as defined by persistent and recurrent symptoms despite on optimal
      asthmatic medications were recruited for the study. GERD was diagnosed by
      symptoms, gastroscopy and 24-h oesophageal pH monitoring. All patients were
      prescribed a course of lansoprazole 30 mg daily for 8 weeks. Improvement to
      treatment was assessed by a change in pulmonary symptom score and also by
      patient's subjective assessment of improvement. RESULTS: Seventeen of 30 (56.7%)
      patients with difficult-to-control asthma were diagnosed with GERD. Pulmonary
      symptom score improved significantly only in patients with GERD (35.0 to 21.0; P
      = 0.002). Twelve of 16 (75%) patients with GERD reported an improvement in asthma
      symptoms; 1 of 11 (9.1%) without GERD reported mild symptom improvement. There
      was no significant change in peak expiratory flow rate and forced expiratory
      volume. CONCLUSIONS: More than half of patients with difficult-to-control asthma
      were diagnosed with GERD. In these patients the severity of asthma improved
      significantly with potent acid suppression therapy. This underlines the critical
      role of acid reflux in this subset of patients with difficult-to-control asthma.

PMID- 16629938
TI  - Survival of patients with early hepatocellular carcinoma treated by percutaneous
      alcohol injection.
AB  - BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma,
      are detected in cirrhotics, the European Association for the Study of the Liver
      guidelines recommend to delay histological confirmation and treatment until they
      increase in size. AIM: To validate this policy by evaluating survival of 450
      cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular
      carcinoma treated by percutaneous alcohol injection. METHODS: Patients were
      sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to <
      or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall
      and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In
      groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months
      (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P =
      0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months
      (P = 0.51), respectively. When patients were sorted by Child status, mean
      survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001).
      CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated
      patients with single, early hepatocellular carcinoma sorted by nodular size
      supports the European Association for the Study of the Liver 'wait-and-see'
      policy for patients with lesions <10 mm, and suggests that allowing the nodules
      to grow prior to taking further diagnostic or therapeutic actions would not harm
      these patients.

PMID- 16629939
TI  - Repeated administration of a vitamin preparation containing glycocholic acid in
      patients with hepatobiliary disease.
AB  - BACKGROUND: Until now, hydrophilic and lipophilic vitamin preparations had to be
      administered separately during total parenteral nutrition. By addition of
      glycocholic acid, a vitamin supplement (Cernevit, Baxter, Heidelberg, Germany)
      was developed that combines all vitamins into one vial. However, little
      information exists about possible consequences of bile acid administration such
      as glycocholic acid, especially if liver disease is pre-existing. AIM: To
      evaluate the effects of total parenteral nutrition with a vitamin preparation
      containing high doses of glycocholic acid in patients with and without liver
      disease. METHODS: In a prospective, randomized-controlled trial, 74 patients, 36
      of them with hepatobiliary disease, received total parenteral nutrition for 16 +/
      11 days, either with Cernevit or control vitamin supplements. Patients were
      closely monitored for clinical and biochemical parameters including serum bile
      acid profiles measured by high-performance liquid chromatography. RESULTS: Serum
      glycocholic acid increased in patients with liver disease treated with Cernevit,
      whereas total bile acids did not significantly change. Other liver function tests
      remained stable during treatment. No adverse events during Cernevit
      administration were noted except for a reversible slight increase of
      transaminases in one patient. CONCLUSIONS: Cernevit was well tolerated after
      repeated dosing, even in patients with severe liver disease. Apart from standard
      controls of liver biochemistry, no specific surveillance is necessary during
      treatment with Cernevit.

PMID- 16629940
TI  - Clinical characteristics of fulminant-type autoimmune hepatitis: an analysis of
      eleven cases.
AB  - BACKGROUND: Although a few adult cases of fulminant-type autoimmune hepatitis
      have been reported, their clinical features and prognosis have remained
      uncertain. AIM: To assess the clinical features and prognosis of patients with
      fulminant-type autoimmune hepatitis. METHODS: Eleven patients (10%) diagnosed
      with fulminant-type autoimmune hepatitis in accordance with the 1999 criteria of
      the International Autoimmune Hepatitis Group were analysed. RESULTS: All 11
      patients were female, with a median age of 53 years. Five patients survived
      without liver transplantation, one received a liver transplantation, and five
      died without liver transplantation. Nine patients (82%) survived for 2 weeks or
      more following diagnosis, without liver transplantation. Except for the patient
      receiving a liver transplantation, serum total bilirubin levels measured during
      the clinical course were significantly higher in non-survivors than in survivors,
      although the accompanying serum alanine aminotransferase levels measured for the
      two groups were similar. Most significantly, serum total bilirubin levels in non
      survivors worsened during days 8-15, while levels in survivors improved during
      the same period. CONCLUSIONS: The short-term prognosis for patients with
      fulminant-type autoimmune hepatitis may be good. However, patients whose serum
      total bilirubin levels worsen during days 8-15 should be considered for liver
      transplantation.

PMID- 16629941
TI  - Long-term study of re-infection following successful eradication of Helicobacter
      pylori infection.
AB  - BACKGROUND: 'Re-infection' with Helicobacter pylori after eradication has been
      estimated to occur in 0-14% of patients, although most so-called 're-infections'
      occur within the first year following 'eradication' and many may actually be due
      to recrudescence of a temporarily suppressed infection. AIM: To study the true re
      infection rate, we have studied re-infection rates after eradication therapy by
      excluding the first year's data, minimizing the possible confounding effect of
      recrudescence. METHODS: All patients tested for H. pylori infection following
      eradication therapy between 1987 and 2004 were evaluated. Testing was carried out
      by urea breath test and gastric biopsy. Patients were included if they were found
      to be negative for H. pylori infection by testing at least 1 year following
      eradication and underwent at least one further test for H. pylori. RESULTS: 1162
      patients met the inclusion criteria with median post-eradication follow-up of 3
      years (1.5-14) including 4668 tests; 3319 years of follow-up were analysed.
      Thirteen cases of re-infection occurred (re-infection rate 0.4% per year).
      CONCLUSIONS: This large study of H. pylori re-infection avoided cases of
      recrudescence by excluding the first post-eradication year. True re-infection is
      probably less common than previously thought.

PMID- 16629942
TI  - A quantitative immunochemical faecal occult blood test is more efficient for
      detecting significant colorectal neoplasia than a sensitive guaiac test.
AB  - BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS;
      Beckman Coulter, Fullerton, CA, USA), is our standard screening test for
      significant colorectal neoplasia. We evaluated an automatically-developed,
      quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical
      Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy
      burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal
      test diagnostic efficacy and costs for identifying significant neoplasia.
      METHODS: Colonoscopies were performed on patients who prepared three daily guaiac
      faecal occult blood tests with or without immunochemical faecal tests. RESULTS:
      Total colonoscopy was performed on 151 subjects who prepared both guaiac and
      immunochemical faecal tests (group 1) and the positive predictive values (PPV)
      were also compared to those of 162 subjects undergoing colonoscopy for positive
      guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity,
      specificity, and PPVs for significant neoplasia with guaiac faecal occult blood
      test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal
      test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy
      examinations needed to detect a significant neoplasm because of positive faecal
      occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the
      cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An
      immunochemical faecal test maintains the high sensitivity of guaiac faecal occult
      blood test, but significantly reduces the colonoscopy burden and screening costs.

PMID- 16629943
TI  - Physicians' approaches to the use of gastroprotective strategies in low-risk non
      steroidal anti-inflammatory drug users.
AB  - BACKGROUND: Many doctors unnecessarily prescribe gastroprotective strategies to
      non-steroidal anti-inflammatory drugs users at low risk of non-steroidal anti
      inflammatory drug-related gastrointestinal complications. AIM: To identify
      factors that predict the overuse of gastroprotective strategies in low-risk non
      steroidal anti-inflammatory drug users. METHODS: We distributed a questionnaire
      to family doctors and general internists consisting of a clinical vignette
      describing a low-risk hypothetical patient with osteoarthritis who was a
      candidate for non-steroidal anti-inflammatory drug therapy. Respondents were
      asked whether they would prescribe this patient a gastroprotective strategy and
      to estimate the annual risk of that patient developing a gastrointestinal
      complication with non-steroidal anti-inflammatory drug use. Respondents
      inappropriately recommending a gastroprotective strategy were compared with
      respondents who opted not to use gastroprotection. RESULTS: We received 340
      responses (response rate of 28.3%), of which 278 supplied analysable data. Thirty
      five percent of respondents inappropriately recommended a gastroprotective
      strategy for the low-risk subject. Inappropriate prescribers were significantly
      more likely to overestimate the risk of gastrointestinal complications with
      traditional non-steroidal anti-inflammatory drugs and this was strongly
      predictive of gastroprotective strategy recommendation in logistic regression.
      CONCLUSIONS: Many doctors inappropriately recommend gastroprotective strategies
      in low-risk non-steroidal anti-inflammatory drug users. Improving doctors'
      awareness of non-steroidal anti-inflammatory drug-associated gastrointestinal
      risks may lead to a decrease in inappropriate utilization of gastroprotective
      strategies in low-risk patients.

PMID- 16629944
TI  - Healing rates for moderate and severe oesophagitis.

PMID- 16629946
TI  - Barrett's oesophagus and HLA-B*0702/HLA-B*0706.

PMID- 16629948
TI  - Effects of mycophenolic acid on inosine monophosphate dehydrogenase I and II mRNA
      expression in white blood cells and various tissues in sheep.
AB  - Mycophenolic acid (MPA) is a mycotoxin commonly found as Penicillium genus
      secondary metabolite in feedstuffs and silages. Feeding with MPA contaminated
      silages may modulate the immune system in the farm animals and can cause appetite
      lost, ketosis, paralysis and abortion. The aim of the present study was to
      characterize the long-term MPA effect on both the inosine monophosphate
      dehydrogenase (IMPDH) isoforms I and II mRNA expression in white blood cells
      (WBC) and various tissue of healthy sheep. In treated animals 300 mg
      MPA/day/sheep was applied. In all investigated tissues the IMPDH I and II mRNA
      was abundant: WBC, spleen, thymus, ileum, jejunum, kidney, liver, pharyngeal and
      mesenterial lymph node. An efficiency-corrected relative quantification of the
      IMPDH types I and II isoforms mRNA were performed by normalizing with the
      constant reference gene expression of beta-actin. High IMPDH I mRNA expression
      levels were seen in kidney > mesenterial lymph node > jejunum > spleen >
      pharyngeal lymph node. Medium and low abundance was found in ileum > WBC > liver
      > thymus. Type II mRNA was highly expressed in liver > thymus > jejunum. In
      pharyngeal lymph node > spleen > ileum > mesenterial lymph node > kidney > WBC
      medium to low IMPDH II mRNA concentrations were detected. Under MPA treatment the
      IMPDH I mRNA expression was not significantly regulated in WBC, only trends of
      down- and upregulation were observed. Surprisingly in jejunum an upregulation
      could be observed (P < 0.05). In pharyngeal lymph node a tendency to
      downregulation was shown. This may be due to frequent ruminant activities and
      frequent exposition of MPA to the pharyngeal lymph nodes. In contrast to type I
      mRNA expression, IMPDH II mRNA was significantly downregulated in ileum (3.4
      fold, P < 0.01) and tendencies in downregulation could be seen in jejunum (5.1
      fold, P = 0.14). In addition, significant downregulation of IMPDH II gene
      expression over the entire feeding experiment could be shown in WBC of MPA
      treated animals compared with untreated animals (P < 0.05). In conclusion, the
      recent study demonstrates that feeding sheep with MPA-contaminated silage did not
      induce IMPDH I mRNA expression in various tissues and blood, except in jejunum,
      but has suppressive effects on IMPDH II mRNA expression in WBC and ileum.

PMID- 16629949
TI  - Effect of Bacillus licheniformis and Bacillus subtilis supplementation of ewe's
      feed on sheep milk production and young lamb mortality.
AB  - The purpose of this pilot study was to evaluate under field conditions the effect
      of a probiotic containing Bacillus licheniformis and Bacillus subtilis on young
      lamb mortality and sheep milk production when administered in the late pregnancy
      and lactation feed of ewes. In a sheep farm, two groups of milking ewes with
      identical genetic material, management, nutrition, health status and similar
      production characteristics were formed. One group (46 ewes) served as control,
      while the other one (48 ewes) served as a probiotic-treated group. Both groups of
      ewes received a similar feeding regiment, but the ewes of the second group were
      additionally offered a probiotic product containing B. licheniformis and B.
      subtilis (BioPlus 2B, Chr. Hansen, Denmark) at the approximate dose of 2.56 x
      10(9) viable spores per ewe per day. Lamb mortality during the 1.5 months
      suckling period, and milk yield during the 2 months of milk collection for
      commercial purposes have been recorded. In the non-treated control group, 13.1%
      mortality was observed versus 7.8% in the probiotic-treated group (P = 0.33),
      with mortality being mainly due to diarrhoea. Microbiological examination of
      diarrhoeic faeces from some of the dead lambs in both groups revealed the
      presence of Escherichia coli. The average daily milk yield per ewe was
      significantly lower in the control group (0.80 l) than that in the probiotic
      treated group (0.93 l) (P < 0.05). Fat and protein content of milk in ewes that
      received probiotics was significantly (P < 0.05) increased compared with
      untreated ewes. It was concluded that supplementing ewe's feed with probiotics
      may have beneficial effect on subsequent milk yields, fat and protein content.

PMID- 16629950
TI  - Immunohistochemical detection of P-glycoprotein (clone C494) in canine mammary
      gland tumours.
AB  - Elevated levels of P-glycoprotein have been reported in multidrug-resistant
      tumours in both humans and dogs. In the present study, we investigated the
      expression of P-glycoprotein in 57 canine mammary gland tumours, 10 mammary gland
      hyperplasia and seven normal mammary glands by immunohistochemistry. Tissue
      sections were incubated with an anti-Pgp monoclonal antibody and visualized with
      En Vision-DAB polymer. Normal and hyperplastic mammary tissues were negative or
      showed slight cytoplasmic immunoreactivity. Neoplastic cells in benign mammary
      tumours showed diffuse cytoplasmic staining, in contrast to malignant tumours
      that showed mainly a membranous staining pattern for Pgp (C494). We observed
      statistically significant differences among all the different groups of tissues
      analysed except for benign tumours versus hyperplasia (P = 0.221). Receiver
      operating characteristic analysis showed that the best cut-off point to
      differentiate the threshold to differentiate negative from positive tissue
      samples was 18.40% of immunostained cells. These results provide a first
      indication that routine evaluation of Pgp expression in canine mammary gland
      tumours, taking into consideration a cut-off point for positivity, may be useful
      for selecting cases for chemotherapy.

PMID- 16629951
TI  - Retrospective study of 156 atrial septal defects in dogs and cats (2001-2005).
AB  - Atrial septal defect (ASD) is a common congenital heart disease (CHD) in humans,
      but considered relatively rare in veterinary medicine. However, modern
      echocardiographic and Doppler techniques currently offer a good view of the
      morphology of the interatrial septum, thus facilitating earlier detection of ASD
      in awake animals. In this context, we carried out a retrospective study of cases
      of recently diagnosed ASD in dogs and cats at the Cardiology Unit of Alfort (2001
      2005) using echocardiography combined with colour Doppler mode. ASD was diagnosed
      in 156 animals and represented 37.7% of all canine and feline CHDs (n = 414). ASD
      was the most common CHD after mitral dysplasia in both species. Boxer and
      Domestic shorthair were the most common canine and feline breeds affected. Most
      defects (98.7%) were secundum-type ASD, without clinical signs in 73.7% of cases.
      The most common clinical signs included systolic murmur heard over the left heart
      base (20.2%), exercise intolerance (7.0%), syncope (5.3%), dyspnoea (2.6%) and
      cough (2.6%). Animals that presented a systolic heart murmur over the left base
      had a significantly larger ASD than others (P < 0.05). These data suggest that
      the incidence of ASD is higher than previously assumed. ASD should be suspected,
      for example, in instances of left basal systolic heart murmur, although its
      clinical and haemodynamic consequences are usually minor.

PMID- 16629952
TI  - Chlamydiales in guinea-pigs and their zoonotic potential.
AB  - The aim was to detect and characterize chlamydial infections in guinea-pigs (GP)
      with ocular disease, study their pathogenicity and zoonotic potential and to test
      for the presence of Acanthamoebae spp. in GP eyes and to investigate whether they
      could act as vectors for Chlamydia-like organisms. Overall 126 GP, of which 77
      were symptomatic, were screened by clinical examination, cytology, gross
      pathology, histology, immunohistochemistry, polymerase chain reaction (PCR) and
      bacteriology. A new Chlamydiaceae-specific intergenic spacer rRNA gene PCR,
      designed to amplify this segment linking the 16S and 23S regions, was performed.
      DNA samples were also received from one owner including samples of his cat and
      rabbit. Guinea-pigs: 48 of 75 symptomatic, but only 11 of 48 asymptomatic GP were
      positive by PCR for Chlamydophila caviae guinea-pig inclusion conjunctivitis
      (GPIC) (P < 0.0001). Eighteen of 75 or 15/48, respectively, were positive for DNA
      from Chlamydia-like organisms. Acanthamoebae-DNA could be found in two GP, of
      which one was symptomatic. Owner, cat and rabbit: Samples of all three species
      were positive by PCR for C. caviae GPIC and the owner's one-day disposable
      contact lenses showed a positive PCR result for the Chlamydia-like organism
      Parachlamydia acanthamoebae. No Acanthamoebae-DNA could be detected. This study
      is the first to describe Chlamydia-like organisms in GP and to detect C. caviae
      GPIC in human, cat and rabbit. Therefore, C. caviae GPIC could pose a zoonotic
      potential. We believe that the finding of C. caviae GPIC in species other than GP
      is probably not unique.

PMID- 16629953
TI  - Primary pulmonary adenocarcinoma metastatic to the uvea, brain and adrenal gland
      in a dog.
AB  - A 10-year-old male Briard dog was presented because of listlessness, abnormal
      gait, fever, inappetence, and seizures. A non-pigmented growth was observed in
      the ventral quadrant of the left iris. Thoracic radiographs revealed multiple
      pulmonary metastases and the owner opted for killing. On necropsy, lung masses
      and nodules in left iris, right adrenal medulla, and brain were detected.
      Histologically the primary tumour was diagnosed as pulmonary adenocarcinoma with
      predominant solid pattern. Metastases to regional lymph nodes, uvea, adrenal
      medulla, and brain were recognized. The metastatic behaviour resembled that
      occurring in humans. To the authors' knowledge, this is the first report of a
      pulmonary adenocarcinoma with metastasis to the uvea in a dog.

PMID- 16629954
TI  - Primary haemangiopericytoma in the pelvic cavity of a dog.
AB  - A 9-year-old female Yorkshire terrier with lameness of the hind leg was examined
      at the local animal hospital in Gwangju, Republic of Korea on March, 2004. The
      radiological findings revealed a mass between the urinary bladder and cervix of
      the uterus. The encapsulated pelvic mass, measuring 4.0 x 3.0 x 2.5 cm was
      surgically removed. Grossly, the mass was white and firm and microscopically
      showed a perivascular whorled pattern of spindle cells. By immunohistochemistry,
      tumour cells tested positive for vimentin and alpha-smooth muscle actin, and
      negative for desmin, S-100, lysozyme and cytokeratin. The tumour was diagnosed
      both histologically and immunohistochemically as a haemangiopericytoma. There
      were no signs of recurrence within 12 months after surgery. This is the first
      case report of a haemangiopericytoma in the pelvic cavity of a dog.

PMID- 16629955
TI  - Vascular hamartoma as the cause of hind limb lameness in a horse.
AB  - We report a 5-year-old gelding with a rare benign tumour of 2-month duration in
      the subcutis of the hind limb that presented with lameness. Physical examination
      revealed normal vital signs. Laboratory findings were within normal ranges. No
      bone abnormalities were detected on radiographic examination of the affected
      area. Bloody fluid was obtained by aspiration. Through an I-shape skin incision
      the tumour was excised en-block. Microscopic study showed a vascular hamartoma
      characterized by cavernous haemangiomatous tissue and proliferation of multiple
      vessels of variable diameter. This report highlights the importance of limb
      vascular hamartoma, as an infrequent lesion, in the differential diagnosis of
      lameness in the horse.

PMID- 16629956
TI  - Ophthalmoscopic characteristics in sheep and goats: comparative study.
AB  - The ocular fundus was examined in 40 goat eyes and 40 sheep eyes by studying
      ophthalmoscopic characteristics and retinograms. Similarities and differing
      characteristics were described. In common: tapetal colour; peripheral yellowish
      area surrounding the Winslow stars; unpigmented areas in the non-tapetal zone; a
      great amount of myelin in the optic disc; the Bergmeister's papilla and the
      holoangiotic retinal vascular pattern. Differences: big size of the Winslow stars
      in goats; myelinizated fibre over the non-tapetal zone in sheep; shape, position
      and myelin distribution of the optic disc; and the presence of a 'primary artery'
      in goats.

PMID- 16629957
TI  - Factors associated with high milk test day somatic cell counts in large dairy
      herds in Brandenburg. II. Milking practices.
AB  - The objective of this study was to examine the influences of different milking
      practices on cow udder health in 80 large dairy herds (range 100-1100 cows) in
      Brandenburg, Germany. Milking practices were evaluated during one complete
      milking using a standardized data capture form. The somatic cell count (SCC) of
      all lactating cows on each farm was determined monthly by the local milk
      recording association 'Landeskontrollverband Brandenburg'. Factor analysis was
      used to investigate the relationship between the different aspects of the milking
      practices. The components extracted by the factor analysis were examined for
      their influence on the SCC of the current month (CMSCC) and the year before the
      visit (YASCC) using univariate analysis of variance. Three components were
      extracted from the milking practices. 'Reasonable use of water' was significantly
      related to CMSCC (P = 0.019) and YASCC (P = 0.003). It included information on
      the use of a hose to clean udders before milking, cleaning of the floor between
      groups and use of water to clean teats. 'Attention of the milkers' was also
      significantly associated with CMSCC (P = 0.012) and YASCC (P = 0.014). It
      included information on the accuracy of mastitis detection by foremilk screening
      and the regular use of post-milking teat and cluster disinfection. The component
      'preparation routines' (method of udder cleaning and forestripping) did not
      significantly influence CMSCC and YASCC. These results indicate that excessive
      use of water in the parlour during milking time is harmful to udder health and
      that the consistency of procedures in the milking parlour presents significant
      room for improvement in large dairy herds in Brandenburg.

PMID- 16629958
TI  - The placebo effect.

PMID- 16629960
TI  - The use of placebo in clinical nursing research.
AB  - AIMS: This paper reviews placebo and placebo effects and their measurement and
      application to nursing. Ethical and methodological issues are also discussed.
      Implications for nursing and recommendations for future study are offered.
      BACKGROUND: Placebos have been used for decades in clinical trials but discussion
      about conceptual, methodological and ethical issues has been comparatively
      scarce. CONCLUSION: It is concluded that true placebo effects are difficult to
      measure and control and the use of credible placebo is sometimes impractical in
      clinical nursing research. This leads to the increased use of usual care as a
      control by researchers. However, more information should be reported in studies
      that use this approach, including the specification of usual care, its monitoring
      and patient adherence. RELEVANCE TO CLINICAL PRACTICE: Where its use is
      considered ethical, safe and feasible, a placebo arm should be included in
      studies of efficacy to distinguish between active and inactive treatment.

PMID- 16629961
TI  - Nursing documentation audit--the effect of a VIPS implementation programme in
      Denmark.
AB  - AIM AND OBJECTIVES: The aim of this paper is to present a study describing
      nurses' adherence to the VIPS model by evaluating the quality of nursing
      assessment, and the quantity of completed nursing care plans. BACKGROUND:
      Numerous efforts have been made over the years to improve nursing documentation
      in Denmark. Hospitals have traditionally based nurses' charting on a rudimentary
      version of the nursing process and on Virginia Henderson's theory of human needs.
      In 2002-2004 the Copenhagen University Hospital, Rigshospitalet, introduced the
      Swedish VIPS model for nursing documentation. VIPS is an acronym for well being,
      integrity, prevention and safety, all of which are seen as major goals for
      nursing care. The model organizes nursing data according to a system of keywords,
      which facilitates storage and retrieval of data. DESIGN AND METHODS: The design
      in this part of the study was retrospective, wherein 50 journals from each of the
      departments of cardiology, neurology, oncology and urology were audited annually
      for three years using the Cat-ch-Ing instrument (n=600). All nursing journals
      were randomly selected by including the first 50 journals at each site given a
      specific date. RESULTS: The nursing documentation significantly improved during
      the course of the study. After the second year the participants used the keywords
      appropriately and correctly according to the VIPS model. Application of primary
      nursing increased during the study. Initial, ongoing and discharge patient status
      improved. The nurses' familiarity with nursing diagnoses, goals and interventions
      increased. CONCLUSIONS: The structured implementation programme significantly
      improved nursing documentation, and the simultaneous training of the entire
      nursing staff shows promise. The VIPS model has prepared the nurses for more
      complex computerized taxonomies and classification systems in the future by
      improving the nurses' analytical skills. Relevance to clinical practice. New
      strategies for improving nursing documentation have been demonstrated.

PMID- 16629962
TI  - An exploration of factors which constrain nurses from research participation.
AB  - AIM: The aim of this study was to explore practising nurses' views on factors
      which they perceived constrained them from research participation. BACKGROUND:
      Many studies reviewed in the literature have taken a quantitative approach and
      have concentrated on why nurses do not use research findings in their practice.
      Of these studies a few included constraints to research use. However, with the
      development of national research strategies for nursing and the drive for the
      profession to develop its own research base, there is a need to understand what
      constrains clinically practising nurses from taking up opportunities to either
      develop their own research or participate in research studies. DESIGN AND METHOD:
      Data were collected during June and July 2004 by means of two focus groups (n=7)
      followed by single interviews (n=7). Analysis was undertaken using a thematic
      approach aided by N-Vivo 2.0. RESULTS AND DISCUSSION: In this study, findings
      revealed six key themes perceived by nurses to constrain from research
      participation: 'Level of support nurses require to be research active', 'Nurses'
      attitudes to undertaking/participating in research', 'The extent of nurses
      knowledge about research', 'Skills to undertake research' and 'Level of
      educational preparation relating to undertaking/participating in research'.
      CONCLUSIONS: In this study, nurses were generally receptive to participating in
      research. However, they felt constrained because of lack of time, lack of peer
      support and limited knowledge and skills of the research process. RELEVANCE TO
      CLINICAL PRACTICE: What is already known on this topic: studies into nurses and
      research have predominantly taken a quantitative approach; many studies have
      aimed to elicit the extent of nurses' use of research findings. WHAT THIS STUDY
      ADDS: this study adds a qualitative perspective; although findings are not
      generalizable, they support quantitative study findings into this subject;
      identifies constraints that require to be overcome for practising nurses to
      actively get involved in research studies.

PMID- 16629963
TI  - Governing time in operating rooms.
AB  - AIM: This paper examines how time is controlled and governed in operating rooms
      through interpersonal communication between nurses and doctors. BACKGROUND: Time
      is a valuable commodity in organizations with improvements often directed towards
      maximizing efficiencies. As a consequence, time can be a source of tension and
      interpersonal conflict as individuals compete for control of its use. METHODS:
      The data in this paper emanate from an ethnographic study that explored a range
      of communication practices in operating room nursing. Participants comprised 11
      operating room nurses. Data were collected over two years in three different
      institutional settings and involved participant observation, interviews and the
      keeping of a personal diary. A deconstructive analysis of the data was
      undertaken. RESULTS: Results are discussed in terms of the practices, in which
      clinicians are engaged in, to govern and control their use of time. The four
      practices presented in this paper include; questioning judgment and timing,
      controlling speed, estimating surgeons' use of time and coping with different
      perceptions of time. CONCLUSIONS: Time and speed were hotly contested by nurses.
      They used their personal knowledge of individual surgeon's habits of time to
      govern and control practice. Nurses thought about surgeons in terms of time and
      developed commonly accepted understandings about the length of surgical
      procedures. They used this knowledge to manage the scheduling of operations in
      the departments and to control the workflow in individual operating rooms.
      Knowledge of individual surgeons was a source of power for operating room nurses.
      RELEVANCE TO CLINICAL PRACTICE: Nurses have more power in the operating room than
      might be imagined but they exercise this power in subtle ways. If operating rooms
      are to work effectively, the operating room team must understand each others'
      work better.

PMID- 16629964
TI  - Model testing on the crisis interventions and actions to prevent medical
      disputes: a Taiwanese nursing perspective.
AB  - AIMS AND OBJECTIVES: This study investigated the contributions of
      comprehensiveness and necessity scales on crisis interventions and actions toward
      nursing practice-related medical disputes in Taiwanese hospitals and
      institutions' demographic characteristics, to overall satisfaction toward nursing
      related crisis management policies and interventions and overall satisfaction
      toward their institution's crisis management system. BACKGROUND: In a health-care
      environment that is focused on cost containment, for overworked nurses and
      understaffed medical wards, patients still expect nurses to provide high quality,
      compassionate care. Patients usually regard nurses as the principal link between
      the technical and interpersonal aspects of their care. However, current hospital
      systems tend to require patients to be self-reliant in managing their own care.
      Patient mistrust of medical care providers might have contributed to the current
      medical error/dispute crisis. METHODS: In this cross-sectional study, the
      subjects were nursing directors of Taiwanese hospitals (197 valid subjects). The
      author developed the questionnaire used in this study. RESULTS: The ordinal
      logistic regression analyses demonstrated that being a public hospital managed by
      the government, being a hospital operated by a corporate body, the more
      comprehensive the technical/structural aspect and the assessment aspect and the
      more needed the psychological aspect, contribute to higher general satisfaction
      levels toward nursing-related crisis management. The more comprehensive the
      strategic aspect and having more acute beds, contributes to higher satisfaction
      levels with their institution's overall crisis management activities.
      CONCLUSIONS: These findings inferred a possible change in a hospital's resource
      allocation or power structure when dealing with issues of patient care quality,
      including nursing practice-related crisis management policies, interventions and
      actions. RELEVANT TO CLINICAL PRACTICE: A good crisis management system may help
      to keep a crisis from worsening, which might lead to a serious situation that
      includes malpractice litigation. It is believed that the questionnaire used in
      this study may be used as a diagnostic tool for assessing a crisis management
      system within a hospital's nursing environment.

PMID- 16629965
TI  - A legacy for the children--attitudes of older adults in the United Kingdom to
      genetic testing.
AB  - AIM: The aim of this study was to assess understanding of genetics and attitudes
      towards genetic testing for clinical and research purposes in a group of older
      adults in the UK. BACKGROUND: Increasingly, genomics will have an impact on the
      diagnosis, prevention and treatment of common diseases and the prescription of
      drugs. The chance of being affected by a medical condition increases with age and
      therefore the use of genetic testing as part of general health-care practice has
      an impact on the older population. METHODS: Older adults were recruited to two
      focus groups (n=7 and n=10 respectively). Focus group discussions were guided by
      a series of questions and were audiotaped. The transcribed data were coded for
      significant statements, which were organized under thematic headings. RESULTS:
      The mean age of participants was 76 years. The main themes to emerge were:
      understanding, approach to genetic testing and conditions for testing. In this
      cohort, the older adults were largely unsure about the underlying scientific
      basis of genetics but were keen to learn more. While enhanced medical knowledge
      could enable preventive measures to be taken and so reduce suffering, it was
      acknowledged that for some people knowing the future could potentially cause
      anxiety and harm. Participants were wary about research being used to benefit
      private companies and voiced ethical concerns about potential coercion to be
      tested and the misuse of science. However, all participants had an altruistic
      approach that influenced their willingness to be tested to benefit others in
      their family or the wider community. Conditions for testing included provision of
      information about the purpose of testing and feedback on the results.
      CONCLUSIONS: Older adults are positive about the opportunities presented by
      genetic testing for clinical reasons and research, but need accurate information
      about the reasons for and implications of such testing. RELEVANCE TO CLINICAL
      PRACTICE: The results of this study confirm the need for nurses to be proactive
      in developing the genetic competencies required to detect potential familial
      disease, make appropriate referrals to genetic services and ensure informed
      consent is obtained for genetic testing.

PMID- 16629966
TI  - Knowledge levels of Korean intensive care nurses towards brain death and organ
      transplantation.
AB  - AIMS AND OBJECTIVES: To develop and examine the reliability and validity of an
      instrument assessing knowledge levels of Korean intensive care unit nurses. To
      conduct a survey with Korean ICU nurses. BACKGROUND: Organ donation from brain
      dead patients is a contentious issue in Korea following recent legal recognition
      of brain death, given the context of a Confucian belief system. Implementation of
      the new Organ Transplant Act has highlighted the importance of identifying Korean
      intensive care unit nurses' knowledge regarding brain death and organ donation.
      DESIGN: Multi-stage multi-method development of an original instrument with a
      cross-sectional analysis survey of participants. METHOD: An 18-item instrument
      was developed based on previous literature and key informant interviews, and
      validated by an expert panel and a pilot study. A survey was conducted with
      Korean intensive care unit nurses (n=520). Principal component analysis with
      varimax rotation was used to determine construct validity. Item-to-total
      correlations and Cronbach's coefficient alpha were used to determine the scale's
      internal consistency. RESULTS: Principal component analysis yielded a two
      component structure: Diagnostic testing and Co-morbid factors of brain death. The
      scale demonstrated acceptable internal consistency for the two components
      (alpha=0.74, 0.64, respectively). Most of the participants had a sound knowledge
      of diagnostic testing for brain death, but demonstrated a lack of knowledge
      regarding co-morbid factors of brain dead patients. CONCLUSIONS: The knowledge
      scale was reliable and valid for this cohort. Further research is warranted in
      related areas of nursing practice. RELEVANCE TO CLINICAL PRACTICE: Effective
      education for intensive care unit nurses is necessary to increase the organ donor
      pool in Korea.

PMID- 16629967
TI  - Does access to bed-chair pressure sensors reduce physical restraint use in the
      rehabilitative care setting?
AB  - BACKGROUND: The common use of physical restraints in older people in hospitals
      and nursing homes has been associated with injurious falls, decreased mobility
      and disorientation. By offering access to bed-chair pressure sensors in
      hospitalized patients with perceived fall risk, nurses may be less inclined to
      resort to physical restraints, thereby improving clinical outcomes. AIMS AND
      OBJECTIVES: To investigate whether the access of bed-chair pressure sensors
      reduces physical restraint use in geriatric rehabilitation wards. DESIGN:
      Randomized controlled trial. METHODS: Consecutively, patients admitted to two
      geriatric wards specialized in stroke rehabilitation in a convalescent hospital
      in Hong Kong, and who were perceived by nurses to be at risk of falls were
      randomly assigned to intervention and control groups. For the intervention group
      subjects, nurses were given access to bed-chair pressure sensors. These sensors
      were not available to control group subjects, as in usual practice. The trial
      continued until discharge. The primary outcomes were the proportion of subjects
      restrained by trunk restraint, bedrails or chair-board and the proportion of
      trial days in which each type of physical restraint was applied. The secondary
      outcomes were the proportions of those who improved in the mobility and transfer
      domains of modified Barthel index on discharge and of those who fell. RESULTS:
      One hundred and eighty subjects were randomized. Fifty (55.6%) out of the 90
      intervention group subjects received the intervention. There was no significant
      difference between the intervention and control groups in the proportions and
      duration of having the three types of physical restraints. There was also no
      group difference in the chance of improving in mobility and transfer ability, and
      of having a fall. CONCLUSION: Access to bed-chair pressure sensor device neither
      reduced the use of physical restraints nor improved the clinical outcomes of
      older patients with perceived fall risk. RELEVANCE TO CLINICAL PRACTICE: The
      provision of bed-chair pressure sensors may only be effective in reducing
      physical restraints when it is combined with an organized physical restraint
      reduction programme.

PMID- 16629968
TI  - Evaluation of a model of nursing care for older patients using participatory
      action research in an acute medical ward.
AB  - AIMS AND OBJECTIVES: The main aim of this study was to improve the quality of
      nursing care for older acutely ill hospitalized medical patients through
      developing, implementing and evaluating a new model of care using a participatory
      action research process. BACKGROUND: One of the challenges of nursing today is to
      meet the health-care needs of the growing older population. It is important to
      consider what quality of nursing care means to older patients if nurses are to
      address gaps between their own perceptions and those of older patients themselves
      and to consider conceptual models of care appropriate for older patients care in
      order to improve the quality of care provided. DESIGN: This study is a mixed
      method triangulated study, involving the use of both quantitative and qualitative
      methods through participatory action research methodology to establish an
      evidence-base for an evolving model of care. METHODS: The model was tested on 60
      acutely ill patients aged at least 65 years. The medical ward nurses selected a
      key reference group including the researcher to facilitate the participatory
      action research process to develop, implement and evaluate a new model of care
      based on Orem's self-care model incorporating the Nurses Improving Care to Health
      System Elders Faculty (Am J Nurs 1994; 94:21) medication protocol to improve the
      nursing care provided for acutely ill older patients. RESULTS: The participatory
      action research process resulted in improved heath-care outcomes for the
      patients, such as significant improvements in activities of daily living
      capabilities between admission to discharge, significant improvements in
      knowledge levels regarding their medication regimes, as well as increased
      satisfaction with nursing care activities as perceived by older patients and
      nursing staff. The implementation of educational sessions during the model of
      care improved the older patient's functional activities and knowledge levels of
      their medication regime prior to discharge. In addition, by repeatedly explaining
      procedures, nurses became more involved with their individual patient's care,
      developing a patient-centred care relationship based on Orem's self-care model.
      CONCLUSIONS: This study demonstrates the efficacy of a new model of nursing care
      in improving the quality of nursing care for older patients in the acute medical
      ward setting. RELEVANCE TO CLINICAL PRACTICE: This study is significant because
      of its evidence-base and demonstrates how the participatory action research
      process empowered nurses to make sustainable changes to their practice. The
      nurses in the study wanted to affect change. The planned change was not dictated
      by management, but was driven by the clinical nursing staff at the 'grass roots'
      level. Therefore, being involved in the decision-making process provided an
      incentive to actively implement change.

PMID- 16629969
TI  - Readmissions: a primary care examination of reasons for readmission of older
      people and possible readmission risk factors.
AB  - AIM: To identify the reasons that may have contributed to the emergency
      readmission of older people to a medical unit, within 28 days of hospital
      discharge. BACKGROUND: The current UK Government has initiatives in place to
      monitor quality and service delivery of NHS organizations. This is achieved by
      setting, delivering and monitoring standards, one of which is 'emergency
      readmission to hospital within 28 days of discharge (all ages), as a percentage
      of live discharges'. DESIGN/METHOD: A year-long study examined reasons for
      unplanned readmission of patients (aged 77 and over) within 28 days of hospital
      discharge. The population was patients, registered with North Bradford PCT
      General Practitioners, readmitted to one of five care of older people wards in
      two local acute trust NHS hospitals. Patient records were scrutinized and data
      related to demography, diagnosis and readmission were collected using a
      structured extraction tool. Data analysis was undertaken using descriptive
      statistics and identification of differences and correlations within the data.
      RESULTS: A pilot study indicated patients readmitted from home vs. other sources
      and patients discharged to home vs. other sources had a significantly shorter
      stay on readmission. The main study showed other significant findings. Patients
      who lived in care were readmitted sooner than those who lived at home: those
      discharged home vs. other sources and agreeing to increased social service
      provision had longer stays on readmission. Shorter length of stay on index
      admission (up to 72 hours) was associated with increased likelihood of earlier
      readmission. CONCLUSIONS: A framework of factors was identified and could be used
      to target resources to meet patients' needs more flexibly. RELEVANCE TO CLINICAL
      PRACTICE: It is possible that the process of targeting resources to 'at-risk'
      patients might enable services to be delivered in a more cost-efficient and cost
      effective way.

PMID- 16629970
TI  - Life satisfaction among older people (65+) with reduced self-care capacity: the
      relationship to social, health and financial aspects.
AB  - AIMS AND OBJECTIVES: This study aimed at investigating life satisfaction and its
      relation to living conditions, overall health, self-care capacity, feeling
      lonely, physical activities and financial resources among people (65+) with
      reduced self-care capacity. BACKGROUND: Knowledge about factors related to low
      life satisfaction among older people with reduced self-care capacity is sparse,
      although this is important in health care and nursing so that the care is adapted
      to their needs and perspective. Previous research has mainly focused on isolated
      aspects such as pain in relation to life satisfaction among older people in
      general and less among so those with reduced self-care capacity in general.
      DESIGN AND METHOD: A subsample of 522 persons was selected from a randomly
      selected cross-sectional survey using a modified form of the Older Americans'
      Resources Schedule and Life Satisfaction Index Z. RESULTS: The mean age in the
      total sample was 77.9; women (79.5) were significantly older than men (77.0). Low
      life satisfaction was found among women, as well as those living in special
      accommodations. Life Satisfaction Index Z was 15.3 (SD 5.6) in the total sample.
      Gender and living conditions did not explain life satisfaction whilst poor
      overall self-reported health and poor financial resources in relation to needs
      had the strongest explanatory value. Also of significant importance were
      loneliness, the degree of reduced self-care capacity and feeling worried.
      CONCLUSION: Life satisfaction in older people with reduced self-care capacity is
      determined by several factors, with social, physical, mental and financial
      aspects probably interacting with each other; especially feeling lonely, degree
      of self-care capacity, poor overall health, feeling worried and poor financial
      resources in relation to needs. These factors need to be considered in the care
      of these people to preserve or improve their life satisfaction. RELEVANCE TO
      CLINICAL PRACTICE: Nursing interventions in terms of preventive home visits,
      rehabilitation, health education directed towards physical, psychological, social
      and economic aspects of importance may help to preserve or improve life
      satisfaction for those with reduced self-care capacity.

PMID- 16629971
TI  - An analysis of clinical teacher behaviour in a nursing practicum in Taiwan.
AB  - AIM AND OBJECTIVES: The aim of this study was to identify and assess the teaching
      behaviours (knowledge, attitudes and skills) observed in nurse educators as they
      taught in the clinical setting. BACKGROUND: Many quantitative studies have
      defined and evaluated teaching effectiveness in the clinical area. Some of these
      studies established instruments to evaluate faculty effectiveness in the clinical
      setting; however, they tended to be so broad that they were of limited use in
      understanding clinical teaching behaviours in nursing education. DESIGN: This
      study explored clinical teaching behaviours in a nursing practicum. Ten nurse
      educators taught 10 students in the medical-surgical unit at a hospital in Taiwan
      for about four weeks. Each teacher was observed by the researcher and one other
      observer for two days during regularly scheduled clinical teaching time. METHODS:
      Data collection and analysis were done by a qualitative approach. Content
      analysis is a process of identifying, coding and categorizing the themes in the
      data. CONCLUSION: The themes of clinical teaching that emerged from data analysis
      included teaching aims (task-oriented and learner-centred), teacher competence
      (teacher knowledge, instructional strategies, planning learning experience,
      teaching priorities, feedback and caring) and teaching commitment (professional
      identity and giving of self). These findings offer a holistic blueprint of
      clinical teaching for nursing faculty members, which will enhance the quality of
      nursing education. RELEVANCE TO CLINICAL PRACTICE: Complexity in nursing
      education has increased as it is challenged to meet the needs of diverse
      populations in rapidly evolving and highly technical health-care settings.
      Clinical teachers must be enabled and empowered to provide students with
      appropriate knowledge and skills to meet the needs of patients. To develop
      students' professional nursing identity now and in the future, nurse educators
      have to commit themselves to both nursing and teaching in clinical settings. More
      nurses need to be prepared for careers in education at the master's and doctoral
      levels.

PMID- 16629972
TI  - Translating person-centred care: a case study of preceptor nurses and their
      teaching practices in acute care areas.
AB  - AIMS AND OBJECTIVES: The research aims to explore how preceptors interpret,
      operationalize, document and teach person-centred care as they guide students
      within an acute surgical environment. BACKGROUND: Person-centred care is a term
      that is widely used in the nursing literature; however, its interpretation in
      nursing practice remains virtually unexplored. This is of great significance to
      nurses in general but to Irish nurses in particular on whom this study is
      focused. As preceptor nurses have been identified as key people in the education
      of clinical students, it was considered important to explore how clinical
      preceptors promote person-centred care to current undergraduate nursing students.
      DESIGN AND METHOD: Using a case study design and a qualitative approach, six
      preceptors were chosen to participate in this study. Data were collected by means
      of participant observation, review of nursing care records and semi-structured
      interviews. Data were analysed in two stages. The first stage involved the
      identification of themes. In the second stage data were analysed using a number
      of propositions to examine and explain what was gleaned from the data in the
      context of what was originally identified in the literature. RESULTS: Findings
      highlighted that preceptors had a limited conception of person-centred care.
      Measures of care reflected the medical model of nursing. Beyond that, preceptors
      expressed care in terms of good manners or respectful etiquette. Preceptors also
      had limited appreciation of what learning entails and were sceptical about
      classroom theory other than what they considered essential for safe practice.
      CONCLUSIONS: This study highlights that preceptors need both internal and
      external support to implement the changes advocated by the Commission in Nursing
      in 1998, the Nursing Education Forum in 2000, the Department of Health and
      Children in 2001 and An Bord Altranais in 2003. RELEVANCE TO CLINICAL PRACTICE:
      Person-centred care is a relatively new concept in nursing and recommended for
      practice. Preceptors need facilitation with its implementation. In an effort to
      promote changes in the delivery of health care, it is suggested that university
      based lecturers empower students to practice evidence-based nursing as students
      and subsequently as qualified nurses.

PMID- 16629973
TI  - Nurse education--the role of the nurse teacher.
AB  - AIM: To explore and analyse the role of the nurse teacher. BACKGROUND: This paper
      examines the issue of clinical credibility among nurse teachers which has been
      ongoing for over a decade. The move of nurse education from colleges of nursing
      to the Higher Education Institutes was seen in 1992. Since then, nurse teachers
      have been faced with the need to juggle the roles of teaching, administration,
      research and clinical support for students. Nursing students within these Higher
      Education Institutes require more than the traditional theoretical classroom
      teaching. Nurse teachers have a role beyond this in encouraging students to link
      theory with practice, and practice with theory. Therein lies a challenge for
      nurse teachers to ensure they remain credible within the clinical setting and
      continue to provide education and support, which is firmly grounded in both
      practice and theory. METHOD: The authors have critically reviewed the evidence
      related to the role of the nurse teacher in an attempt to identify key concepts
      and ideas, assumptions, supporting examples and the implications for their role.
      CONCLUSION: The role of the nurse teacher, it would appear, is a dynamic one that
      needs to engage actively the needs of the student. Nurses therefore need to be
      dynamic in their approach in order to respond to both local and global demands
      and ensure that students become competent, professional, knowledgeable and caring
      in their approach. RELEVANCE TO CLINICAL PRACTICE: This paper demonstrates the
      complex and ever changing role of the nurse teacher. This paper attempts to help
      nurse teachers understand the complex nature of their role.

PMID- 16629974
TI  - Commentary on West E, Barron DN and Reeves R (2005) Overcoming the barriers to
      patient-centred care: time, tools and training. Journal of Clinical Nursing 14,
      435-443.

PMID- 16629975
TI  - Commentary on Lambert V and Glacken M (2005) Clinical education facilitators: a
      literature review. Journal of Clinical Nursing 14, 664-673.

PMID- 16629976
TI  - Commentary on Irvine F (2005) Exploring district nursing competencies in health
      promotion: the use of the Delphi technique. Journal of Clinical Nursing 14, 965
      975.

PMID- 16629978
TI  - Commentary on Irvine (2005) Exploring district nursing competencies in health
      promotion: the use of the Delphi technique. Journal of Clinical Nursing 14, 1-11.

PMID- 16629979
TI  - To Thompson D (2004) commentary on Lau-Walker (2004).

PMID- 16629980
TI  - To Holroyd E (2005) commentary on Lee et al. (2004).

PMID- 16629981
TI  - Detection and molecular characterization of porcine enteric calicivirus in Korea,
      genetically related to sapoviruses.
AB  - Porcine enteric calicivirus (PECV) shares morphological and genetical
      similarities with Sapoviruses (SVs), which are the leading cause of epidemic, non
      bacterial gastroenteritis in children worldwide. The aim of this study was to
      identify the prevalence of PECV infection in pig farms in Korea, and to compare
      the evolutionary inter-relationships between Korean PECVs and other
      caliciviruses. Among 102 diarrhoeic faecal samples of sucking (n = 50) and weaned
      (n = 52) piglets from 31 different farms in Korea, five samples (4.9%) were
      detected positive by reverse-transcriptase polymerase chain reaction (PCR), but
      nine (8.8%) by nested-PCR. Furthermore, we found that Korean PECVs are closely
      related to SVs.

PMID- 16629982
TI  - Detection of bovine torovirus in neonatal calf diarrhoea in Lower Austria and
      Styria (Austria).
AB  - Faeces of 230 calves with and without diarrhoea collected during the winter
      period 2004/2005 in 100 Austrian farms (Styria and Lower Austria) were examined
      for viral, bacterial and parasitic enteropathogens. Torovirus-specific nucleic
      acid confirmed by reverse transcriptase-polymerase chain reaction was found in 12
      of 230 calves (5.2%). Ten of these calves were clinically ill, several of them
      showing signs of dehydration and abnormal faecal consistency at the time of
      sampling. Computer assisted analysis of two nucleotide sequences obtained from
      Austrian bovine samples revealed 93% similarity to Breda strain, but only 71% or
      52% similarity to Equine Berne or Porcine Markelo torovirus strains respectively.
      Phylogenetic analysis grouped Austrian torovirus samples into the Bovine
      torovirus cluster indicating the first detection of Bovine torovirus in Austria.
      In addition, the following agents were detected in bovine faecal samples: Bovine
      coronavirus, 25.7%; Escherichia coli, 17%; Cryptosporidium spp., 11.7%; Eimeria
      spp., 10.4%; Rotavirus, 9.1%; Clostridium perfringens, 9.1% and Giardia spp.,
      6.1%. Salmonella spp. was not detected.

PMID- 16629983
TI  - Seroprevalance and identification of influenza A virus infection from migratory
      wild waterfowl in China (2004-2005).
AB  - Outbreaks of a highly pathogenic avian influenza (H5N1) were reported in birds in
      more than eight Asian countries. We sought to identify the origin of this
      infection, and herein report the results of serological and virological
      monitoring of migrant wild waterfowl in mainland China. From a total of 493 serum
      samples, collected from 15 migratory wild waterfowl species for 9 months (from
      June 2004 to May 2005) in mainland China, we detected only low-level antibodies
      against influenza subtypes H2, H9 and H10 in the relict gull, little egret, black
      crowned night heron, bar-tailed godwit, whimbrel and the common greenshank. No
      virus was identified from the 1052 cloacal and oropharyngeal swabs except dead
      bar-headed geese. These data show that the influenza type A virus subtypes H2-H13
      did not circulate at detectable levels within the sampled population.

PMID- 16629984
TI  - Limited pathogenicity of usutu virus for the domestic goose (Anser anser f.
      domestica) following experimental inoculation.
AB  - Usutu virus (USUV) is a mosquito-borne flavivirus of the Japanese encephalitis
      virus group, which has been associated with avian mortality in Austria since
      2001. The affected birds are predominantly Eurasian blackbirds (Turdus merula).
      In the present study, the pathogenicity of USUV for domestic geese (Anser anser
      f. domestica) was investigated. Eleven 2-week-old geese were inoculated
      intramuscularly with 5 x 10(4) 50% tissue culture infectious dose of USUV strain
      Vienna-2001 blackbird. No clinical signs were seen during the observation period.
      Four inoculated and one in-contact geese died without preceding clinical signs.
      Two of the deaths could be attributed to bacterial septicaemia and strangulation,
      respectively. The cause of death of two experimental and one in-contact animals
      remained unclear, but lack of evidence for viral lesions and viral antigen in
      their tissues argued against association with the USUV infection. Although in
      organs of the majority of inoculated geese (9/11) USUV was detected by reverse
      transcriptase-polymerase chain reaction, immunohistochemistry for USUV antigen
      was negative in all tissues of all geese. Evidence of plasma viraemia or viral
      excretion was found in one goose only. Seroconversion was detected in three
      inoculated geese 10 days post-inoculation. Geese placed in contact with
      inoculated geese and control animals did not exhibit USUV in their internal
      organs or plasma and lacked USUV-specific antibodies. This experiment shows that
      USUV is able to replicate in geese, but does not induce clinical disease, is
      unlikely to induce mortality, and only infrequently leads to viraemia or virus
      shedding.

PMID- 16629985
TI  - Determination of the inflammatory potential of bioaerosols from a duck-fattening
      unit by using a limulus amebocyte lysate assay and human whole blood cytokine
      response.
AB  - Inhalation of bioaerosols from animal houses can induce acute inflammatory
      reactions in the respiratory tract. Determination of the concentration of
      airborne endotoxins is widely used to characterize this risk. In this study, the
      activity of bioaerosol samples from a duck-fattening unit to induce interleukin
      1beta (IL-1beta) in human blood and to react with Limulus Amebocyte Lysate (LAL)
      was investigated. The activity detected in the whole blood assay correlated well
      with the endotoxic activity found in the LAL assay (Spearmen's rho = 0.902).
      However in all samples, the inflammation-inducing potential was overestimated by
      the LAL assay. It is assumed that this overestimation could be, in part, a result
      of an overestimation of the inflammatory potential of endotoxins originating from
      Pseudomonadaceae by the LAL assay. Pseudomonadaceae were regularly isolated from
      the air of the duck-fattening unit. The results presented here indicate that the
      whole blood assay can be used besides the LAL assay as an additional method to
      characterize the inflammation-inducing potential of bioaerosols.

PMID- 16629986
TI  - Phenotypic and genotypic anti-microbial resistance profiles of campylobacters
      from untreated feedlot cattle and their environment.
AB  - Anti-microbial resistance is an emerging public health issue. Farmed animals may
      act as reservoirs and potential sources of anti-microbial resistant
      Campylobacters. The aim of this study was to investigate the anti-microbial
      resistance profile of cattle and environmental Campylobacter isolates from normal
      untreated feedlot cattle, the role of the gyrA Thr-86-Ile mutation in
      ciprofloxacin-resistant Campylobacter jejuni isolates and the involvement of the
      tripartite CmeABC efflux system for multi-resistant C. jejuni isolates. The
      phenotypic anti-microbial resistance testing was carried out on 500 Campylobacter
      isolates (445 cattle isolates and 55 environmental isolates). In general, there
      was a higher level of anti-microbial resistance for the environmental isolates
      compared with the animal isolates, 45% of the animal isolates were resistant to
      one or more of the seven anti-microbials compared with 84% of the environmental
      isolates. The combined cattle and environmental Campylobacters had 34 (6.8%)
      isolates resistant to three or more of the seven anti-microbials tested on all
      isolates and 11 (2.2%) isolates were resistant to the seven anti-microbials.
      There was a substantial level of ciprofloxacin-resistant Campylobacters in both
      animal (8.5%) and environmental (21.8%) isolates. The gyrA Thr-86-Ile mutation
      was only present in five of 22 ciprofloxacin-resistant C. jejuni isolates
      investigated. No multi-drug-resistant associated mutation was detected in the
      CmeB or the CmeR regions investigated. In conclusion, our study observed a
      substantial level of Campylobacter anti-microbial resistance, highlighting the
      need for an active anti-microbial surveillance program for food animals in
      Ireland and the importance of the chosen sampling point can have on the findings
      of such a program.

PMID- 16629987
TI  - Toxoplasma gondii and Chlamydophila abortus in caprine abortions in Tobago: a
      sero-epidemiological study.
AB  - A sero-epidemiological study was conducted on a goat farm that experienced an
      abortion epidemic in the 2005 breeding season in Tobago. Serum samples of goats
      (aborting and non-aborting) and cats were collected, in addition to the use of
      stored sera from the farm sampled in 2003 and 2004. Farm records on the
      reproductive and mortality rates for year 2003, 2004 and 2005 were also reviewed.
      The sera were screened for Toxoplasma gondii antibodies using the latex
      agglutination test (LAT), Chlamydophila abortus with an enzyme-linked
      immunosorbent assay (ELISA) and Brucella abortus using the buffered plate
      agglutination test (BPAT). Farm records revealed that for the period 2003-2005,
      the average kid per doe rate decreased from 2.1 to 1.5, the mortality rate
      increased from 6.3% in 2002 to 19.4% in 2004 and the fertility rate decreased
      from 98-99% (2002-2004) to 89% (2005). There was a dramatic increase in the
      abortion rate from <1% (2002, 2003 and 2004) to 29.2% (2005). Of a total of 161
      sera tested comprising 12 from 2003, 89 from 2004 and 70 from 2005, 0 (0.0%), 21
      (23.6%) and 45 (64.3%) were positive for T. gondii agglutinins (i.e. titres > or
      =1 : 64) and the differences were statistically significant (P < 0.05; chi(2)).
      Of all serum samples tested, only 1 (1.1%) of 89 from 2004 was positive for C.
      abortus while all the sera tested were negative for B. abortus. Amongst the 24
      does which aborted in 2005 and were available for testing in mid-2005, 15 (62.5%)
      had reciprocal titres of > or =1 : 2048, three (12.5%) each had titres of 1 :
      1024, 1 : 256 and < or =1 : 16 i.e. negative. The seroprevalence and titres of
      does that aborted, 20 (87.0%) of 23, all with titres > or =1 : 256 suggesting
      current infection, were statistically significantly (P < 0.05; chi(2)) higher
      than was detected amongst does that delivered normal kids, 25 (53.25) of 47 with
      22 (48.8%) having titres of > or =1 : 256. One (50.0%) of two cats caught and
      tested was seropositive with a reciprocal titre of 128. This is considered the
      first documentation of T. gondii agglutinins in caprine abortion as well the
      detection of C. abortus antibodies from livestock in Trinidad. It is concluded
      that of the three zoonotic abortifacient pathogens tested for, T. gondii appeared
      to have played some aetiological role in the abortion epidemic investigated.

PMID- 16629988
TI  - Detection of Salmonella spp. in stray dogs in Bursa Province, Turkey: first
      isolation of Salmonella Corvallis from dogs.
AB  - The prevalence and antimicrobial sensitivity of Salmonella spp. in stray dogs in
      Bursa province, Turkey were determined from a total of 82 faecal samples by
      bacteriological methods. Of the dogs, nine (11%) were positive for salmonellae
      carrying. All Salmonella isolates were serotyped as S. Corvallis, and were
      sensitive to amoxycillin/clavulanic acid, ampicillin, cephalothin,
      chloramphenicol, enrofloxacin, gentamicin, kanamycin, nalidixic acid, neomycin,
      oxytetracycline and trimethoprim/sulphamethoxazole, while 66.7% of them were
      resistant to streptomycin. It was concluded that stray dogs could be an important
      carrier of salmonellae as well as a source of human salmonellosis in Turkey.
      Additional studies are needed to clarify the epidemiological relationship between
      S. Corvallis isolated from dogs and humans with regard to public health. This is
      the first report on the isolation of S. Corvallis from dogs in the country.

PMID- 16629989
TI  - Genetic characterization of Anaplasma (Ehrlichia) platys in dogs in Spain.
AB  - This paper reports the first genetic characterization of Anaplasma (Ehrlichia)
      platys in Spain from a naturally infected dog. The dog presented clinical signs
      compatible with canine ehrlichiosis. After DNA extraction and PCR amplification,
      16S rRNA gene and citrate synthase gene ( gltA) of this agent were amplified. The
      GenBank accession number for the nucleotide sequence of the 16S rRNA gene of this
      strain is AY530806. The A. platys strains registered in France and Japan showed
      the highest similarity to the 16S rRNA gene sequence obtained from the Spanish
      strain. In the amplification of the gltA gene, a 1443 bp fragment was obtained,
      and three nucleotide differences were detected in comparison with other strains
      sequences. These data confirm the presence of A. platys in a dog showing clinical
      signs compatible with ehrlichiosis in Spain.

PMID- 16629990
TI  - Evaluation of some coagulation parameters in hepatic coccidiosis experimentally
      induced with Eimeria stiedai in rabbits.
AB  - The objective of this study was to evaluate some coagulation parameters in
      hepatic coccidiosis experimentally induced with Eimeria stiedai in rabbits.
      Fourteen healthy New Zealand rabbits were equally divided into two groups. One
      group received no treatment, the other group was orally inoculated with 40 000
      sporulated oocysts of E. stiedai in a 1 ml inoculum using a catheter. At day 24
      after inoculation, blood samples were collected into sodium citrate-containing
      tubes to evaluate some coagulation parameters. Although statistically not
      significant, infected rabbits had prolonged prothrombin time and activated
      partial thromboplastin time compared with rabbits in the control group. A
      significant reduction (P < 0.05) was observed in the level of fibrinogen of
      infected rabbits compared with that of the controls. A slight decrease in
      thrombocyte counts of infected rabbits was not statistically significant.

PMID- 16629991
TI  - Gnotobiotically grown aquatic animals: opportunities to investigate host-microbe
      interactions.
AB  - The culture of aquatic organisms is still hampered by the occurrence of
      unpredictable diseases in their early life stages, which are responsible for
      massive mortalities and considerable economic losses. A better understanding of
      the host-microbe interactions is certainly essential to develop effective
      solutions of disease control for the aquaculture industry. As demonstrated in
      terrestrial animals, the use of gnotobiotic systems (animals cultured in axenic
      conditions or with a known microflora) can be an excellent tool to extent the
      understanding of the mechanisms involved in host-microbe interactions and to
      evaluate new treatments of disease control. Several aquatic animals were cultured
      so far in germ-free conditions, such as fish, molluscs, crustaceans, rotifers,
      echinoderms, cnidarians, turbellarians, ascidians and echiurans. The aim of the
      present review is to recapitulate the findings obtained with gnotobiotic aquatic
      animals over the last decades, with special emphasis to the host-microbe
      interactions, as well as the perspectives for future research in this field. In
      addition, the procedures utilized to culture axenic aquatic animals and to verify
      contaminations are summarized, and the standardization of these procedures is
      proposed.

PMID- 16629992
TI  - Sensitive and rapid detection of Flavobacterium columnare in channel catfish
      Ictalurus punctatus by a loop-mediated isothermal amplification method.
AB  - AIMS: To evaluate the loop-mediated isothermal amplification method (LAMP) for
      rapid detection of Flavobacterium columnare and determine the suitability of LAMP
      for rapid diagnosis of columnaris infection in channel catfish, Ictalurus
      punctatus. METHODS AND RESULTS: A set of four primers, two outer and two inner,
      were designed specifically to recognize 16S ribosomal RNA gene of this pathogen.
      Bacterial genomic DNA templates were prepared by hot lysis in a lysis buffer.
      Amplification of the specific gene segments was carried out at 65 degrees C for 1
      h. The amplified gene products were analysed by agarose gel electrophoresis and
      detected by staining gels with ethidium bromide. A PCR assay was also included in
      this study. Our results demonstrate that the ladder-like pattern of bands from
      204 bp specific to the Fl. columnare 16S ribosomal RNA gene was amplified. The
      detection limit of the LAMP assay was comparable to that of PCR in prepared
      genomic DNA reactions. In addition, this optimized LAMP assay was able to detect
      the Fl. columnare 16S ribosomal RNA gene in experimentally infected channel
      catfish. CONCLUSIONS: The LAMP assay for Fl. columnare detection in channel
      catfish was established. SIGNIFICANCE AND IMPACT OF THE STUDY: Because LAMP assay
      is a rapid, sensitive, specific, simple and cost-effective assay for Fl.
      columnare detection in channel catfish, it is useful for rapid diagnosis of Fl.
      columnare in fish hatcheries and the field.

PMID- 16629993
TI  - Isolation and characterization of a novel banana rhizosphere bacterium as fungal
      antagonist and microbial adjuvant in micropropagation of banana.
AB  - AIM: Isolation and characterization of a bacterial isolate (strain FP10) from
      banana rhizosphere with innate potential as fungal antagonist and microbial
      adjuvant in micropropagation of banana. METHODS AND RESULTS: Bacterium FP10 was
      isolated from the banana rhizosphere and identified as Pseudomonas aeruginosa
      based on phenotypic, biochemical traits and sequence homology of partial 622-bp
      fragment of 16S ribosomal DNA (rDNA) amplicon, with the ribosomal database
      sequences. Strain FP10 displayed antibiosis towards fungi causing wilt and root
      necrosis diseases of banana. Production of plant growth hormone, indole-3-acetic
      acid (IAA), siderophores and phosphate-solubilizing enzyme in FP10 was
      determined. Strain FP10 tested negative for hydrogen cyanide, cellulase and
      pectinase, the deleterious traits for plant growth. Screening of antibiotic genes
      was carried out by polymerase chain reaction using gene-specific primers.
      Amplification of a 745-bp DNA fragment confirmed the presence of phlD, which is a
      key gene involved in the biosynthesis of 2,4-diacetylphloroglucinol (DAPG) in
      FP10. The antibiotic produced by FP10 was confirmed as DAPG using thin layer
      chromatography, high performance liquid chromatography and Fourier transform
      infrared and tested for fungal antibiosis towards banana pathogens. Procedures
      for encapsulation of banana shoot tips with FP10 are described. CONCLUSIONS:
      Strain FP10 exhibited broad-spectrum antibiosis towards banana fungi causing wilt
      and root necrosis. DAPG by FP10 induced bulb formation and lysis of fungal
      mycelia. Encapsulation of banana shoot tips with FP10 induced higher frequency of
      germination (plantlet development) than nontreated controls on Murashige and
      Skoog basal medium. Treatment of banana plants with FP10 enhanced plant height
      and reduced the vascular discolouration as a result of Fusarium oxysporum f. sp.
      cubense FOC. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of the innate
      potential of fungal antibiosis by DAPG antibiotic and production of siderophore,
      plant-growth-promoting IAA and phosphatase, the strain FP10 can be used as
      biofertilizer as well as a biocontrol agent.

PMID- 16629994
TI  - Rice endophyte Pantoea agglomerans YS19 promotes host plant growth and affects
      allocations of host photosynthates.
AB  - AIMS: The aims of the study were to identify the effects of rice endophyte
      Pantoea agglomerans YS19 on host plant growth and allocations of photosynthates.
      METHODS AND RESULTS: Endophytic diazotrophic YS19 showed nitrogen-fixing activity
      in N-free medium, and produced four categories of phytohormones which were indole
      3-acetic acid, abscisic acid, gibberellic acid and cytokinin in Luria-Bertani
      medium. Inoculation of YS19 improved the biomass of the 12-day-cultivated host
      rice seedlings by 63.4% on N-free medium or by 18.7% on N-supplemented medium.
      Spraying of YS19 cell culture onto the rice plants at the premilk stage enhanced
      the transportation of the photosynthetic assimilation product from the source
      (flag leaves) to the sink (stachys) significantly. The formation of the plant
      sink was obviously inhibited when YS19 cell culture was applied at the late milk
      stage. CONCLUSIONS: This research suggests that endophyte YS19 promotes host rice
      plant growth and affects allocations of host photosynthates. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These findings suggested that YS19 possesses the potential
      for increasing rice production in field application. Meanwhile, a suitable plant
      growth stage must be selected for the foliar spraying of YS19 cell culture.

PMID- 16629995
TI  - Isolation and characterization of rhizosphere bacteria with potential for
      biological control of weeds in vineyards.
AB  - AIMS: Deleterious rhizosphere inhabiting bacteria (DRB) have potential to
      suppress plant growth. This project focuses on the isolation of DRB with
      potential for development as commercial products for weed control. METHODS AND
      RESULTS: Bacteria were isolated from the rhizosphere, rhizoplane, and
      endorhizosphere of seedlings and mature plants of wild radish (Raphanus
      raphanistrum), annual ryegrass (Lolium rigidum) and capeweed (Arctotheca
      calendula) growing in vineyards in the Swan Valley, Western Australia. A majority
      (81.5%) of the 442 strains was obtained from either rhizospheres or rhizoplanes.
      Rapid screening techniques were developed to evaluate in the laboratory and
      glasshouse the effects of bacteria on plants. Strains were screened in the
      glasshouse for deleterious effects on annual ryegrass, wild radish, grapevine
      rootlings (Vitis vinifera) and the legume cover crop subterranean clover
      (Trifolium subterraneum). Three strains were identified using the Biolog system
      and 16S rRNA gene sequencing as two strains of Pseudomonas fluorescens (WSM3455
      and WSM3456) and one strain of Alcaligenes xylosoxidans (WSM3457). One of the P.
      fluorescens (WSM3455) strain produced hydrogen cyanide, an inhibitor of plant
      roots and a broad-spectrum antimicrobial compound. CONCLUSIONS: Three strains
      specifically inhibited wild radish but had no significant deleterious effects on
      either grapevine rootlings or subterranean clover. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study suggested manipulation of the weed seedling rhizosphere using
      identified DRB as a potential biocontrol agent for wild radish.

PMID- 16629996
TI  - Detection of Legionella spp. by fluorescent in situ hybridization in dental unit
      waterlines.
AB  - AIMS: To confirm the presence of viable Legionella spp. in dental unit waterlines
      (DUWL) using fluorescent in situ hybridization (FISH) and compare this method
      with culture approach and also to validate the utility of an enrichment to
      increase FISH sensitivity. METHODS AND RESULTS: Water samples from 40 dental
      units were analysed. Three different techniques for detecting Legionella spp.
      were compared: (i) culture approach, (ii) direct FISH and (iii) FISH with a
      previous R2A medium enrichment (R2A/FISH). The FISH detection was confirmed by
      PCR. The use of the direct FISH does not improve significantly the detection of
      legionellae when compared with the culture. On the contrary, when R2A/FISH was
      performed, sensitivity was, respectively, two- and threefold higher than that
      with the direct FISH and culture approach. Using R2A/FISH, 63% of water samples
      analysed showed a contamination by legionellae. CONCLUSIONS: Legionellae
      detection by direct FISH and R2A/FISH in dental unit water is possible but is
      more rapid and more sensitive (R2A/FISH) than the culture approach. SIGNIFICANCE
      AND IMPACT OF THE STUDY: R2A/FISH showed that several pathogens present in DUWL
      are viable but may not be culturable. Unlike PCR, R2A/FISH is designed to detect
      only metabolically active cells and therefore provides more pertinent information
      on infectious risk.

PMID- 16629997
TI  - Nucleotide excision repair and photoreactivation in the entomopathogenic fungi
      Beauveria bassiana, Beauveria brongniartii, Beauveria nivea, Metarhizium
      anisopliae, Paecilomyces farinosus and Verticillium lecanii.
AB  - AIMS: To compare the DNA repair capabilities of the entomopathogenic fungus (EPF)
      bassiana to the EPF Beauveria brongniartii, Beauveria nivea, Metarhizium
      anisopliae, Paecilomyces farinosus, Verticillium lecanii, and the fungi
      Aspergillus niger and Neurospora crassa. METHODS AND RESULTS: Germination of B.
      bassiana conidiospores following ultraviolet (UV) irradiation was used to show
      that nucleotide excision repair and photoreactivation decrease the post-UV
      germination delay. These two modes of repair were characterized and compared
      between the aforementioned EPF, A. niger and N. crassa using a physiological
      assay where per cent survival post-UV irradiation was scored as colony forming
      units. CONCLUSIONS: The results showed B. bassiana and M. anisopliae are the most
      UV-tolerant EPF. The DNA repair capabilities indicated that EPF do not have all
      DNA repair options available to fungi, such as A. niger and N. crassa.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A key factor detrimental to the survival of
      EPF in agro-ecosystems is UV light from solar radiation. The EPF literature
      pertaining to UV irradiation is varied with respect to methodology, UV source,
      and dose, which prevented comparisons. Here we have characterized the fungi by a
      standard method and established the repair capabilities of EPF under optimal
      conditions.

PMID- 16629998
TI  - The assessment of airborne bacterial contamination in three composting plants
      revealed site-related biological hazard and seasonal variations.
AB  - AIMS: The purpose of this study was to evaluate the degree of bacterial
      contamination generated by three Italian composting plants (1, 2 and 3) in two
      different seasons and to assess the health risk for the employees. METHODS AND
      RESULTS: Aerosols samples were collected with an agar impact sampler. Several
      plant sites and external upwind and downwind controls were examined. Total colony
      forming counts of mesophilic and thermophilic bacteria, actinomycetes and
      streptomycetes, Gram-negatives, coliforms and sulfite-reducers were determined.
      Selective media were used in order to isolate pathogenic bacteria. The levels of
      total mesophilic and thermophilic micro-organisms ranged between 33 and >40,000
      CFU m(-3) in plant 1, 39 and 18,700 CFU m(-3) in plant 2 and 261 and 6278 CFU m(
      3) in plant 3. Strains of Escherichia coli, Staphylococcus aureus and Clostridium
      perfringens were also found. CONCLUSIONS: The plants monitored in this study have
      proved to be sources of aerosolized bacteria. The activities involving mechanical
      movement of the composting mass and the indoor activities were of greatest
      potential risk. In all the studied plants, a statistically significant dependence
      was found between the bacterial contamination and the season for some or almost
      all the analysed parameters, but a clear seasonal trend could not be observed.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides broad evidence of
      bacterial aerosol dispersion and site-related biological hazards that may be
      useful to the regional government to implement regulations on worker safety in
      composting plants.

PMID- 16629999
TI  - Total bacterial and species-specific 16S rDNA micro-array quantification of
      complex samples.
AB  - AIMS: We describe a novel DNA-micro-array-based method that targets 16S rDNA to
      quantify changes in both the total bacterial DNA and the species-specific DNA
      composition. METHODS AND RESULTS: Quantifications were achieved by combining
      competitive PCR for quantifying total bacterial DNA with quantification of
      species-specific DNA composition based on signature 16S rDNA sequences. We
      constructed 11 different probes, which were evaluated on 21 different strains, in
      addition to complex samples. The signals obtained with sequence-specific
      labelling of the probes corresponded well with what should be expected based on
      16S rDNA phylogenetic reconstruction. The quantification of species-specific DNA
      composition showed that the micro-array approach could be used to accurately
      determine differential growth of bacteria in mixed samples. We analysed samples
      containing mixtures of Lactococcus lactis and different species of
      propionibacteria during a 2-week incubation period. Lactococcus lactis grew fast,
      reaching a maximum after 12 h, Propionibacterium acidipropionici and
      Propionibacterium freudenreichii reached a maximum after 48 h, whereas
      Propionibacterium jensenii showed a slow increase during the whole growth period.
      The 16S rDNA total bacterial DNA quantification was compared with real-time PCR,
      absorbance measurements (ABS600) and colony forming units (CFU). CONCLUSION: The
      accuracy of the array approach was in the same range or better than the
      alternative techniques. The potential of the 16S rDNA micro-array method was
      further demonstrated using a liquid cheese model. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is to our knowledge the first time quantification of the total
      bacterial DNA and the species-specific DNA compositions of mixed populations have
      been achieved in the same assay.

PMID- 16630000
TI  - Population distributions of minimum inhibitory concentration--increasing accuracy
      and utility.
AB  - AIMS: To generate continuous minimum inhibitory concentration (MIC) data that
      describes the discrete nature of experimentally derived population MIC data.
      METHODS AND RESULTS: A logistic model was fitted to experimentally derived MIC
      population cumulative distributions from clinical isolates of Haemophilus
      influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Staphylococcus
      aureus (European Committee on Antimicrobial Susceptibility Testing, BSAC and
      MYSTIC population susceptibility databases). From the model continuous
      distributions of population susceptibility were generated. The experimentally
      observed population distributions based on discrete MIC could be reproduced from
      this underlying continuous distribution. Monte Carlo (MC) simulation was used to
      confirm findings. Where the discrete experimental data contained few or no
      isolates with MIC greater or less than the antimicrobial concentration range
      tested, the true mean MIC was a factor of 0.707 times that normally reported and
      may be of little clinical significance. Where data contained isolates beyond the
      range of concentration used, the true MIC was dependent on the SD and the number
      of isolates and could be clinically significant. Subpopulations of differing
      susceptibilities could be modelled successfully using a modified logistic
      equation: this allows a more accurate examination of the data from these
      databases. CONCLUSIONS: The mean MIC and SD of population data currently reported
      are incorrect as the method of obtaining such parameters relies on normally
      distributed data which current MIC population data are not. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Obtaining the distribution parameters from the underlying
      continuous distribution of MIC can be carried out using a simple logistic
      equation. MC simulation using these values allows easy visualization of the
      discrete data. The analyses of subpopulations within the data should increase the
      usefulness of horizontal studies.

PMID- 16630001
TI  - Evaluation of the Cepheid GeneXpert system for detecting Bacillus anthracis.
AB  - AIMS: The Cepheid GeneXpert is a four-site, automated sample preparation and real
      time PCR detection system. In this study, the capability of the GeneXpert to
      isolate and detect nucleic acid from Bacillus anthracis Ames spores was assessed.
      METHODS AND RESULTS: A four-plex, dried-down bead cartridge containing PCR
      reagents specific for the pXO1 and pXO2 plasmids as well as sample processing and
      inhibition controls was evaluated. For B. anthracis Ames spores harbouring pXO1
      and pXO2, samples containing 68 CFU per ml (148 spores per ml) were positive in
      all four replicates. A limited cross-reactivity panel, which included closely
      related Bacillus species, was also tested to determine the specificity of the
      pXO1 and pXO2 assays. No cross-reactivity occurred. Further, B. anthracis Sterne
      spore samples were analysed to compare results when processed using the GeneXpert
      to those run directly on the Cepheid SmartCycler without sample processing. The
      GeneXpert detection capability was three logs lower than the SmartCycler
      indicating the benefit of incorporating a nucleic acid extraction procedure.
      CONCLUSIONS: This study demonstrates that the GeneXpert is a rapid and reliable
      system for simultaneously detecting the B. anthracis virulence plasmids pXO1 and
      pXO2. SIGNIFICANCE AND IMPACT OF THE STUDY: The GeneXpert is the only platform
      currently available that is capable of both nucleic acid purification and real
      time PCR detection enclosed within a single system. Further, all sample
      manipulations are automated, thus reducing errors associated with manual
      processing.

PMID- 16630003
TI  - Observations on the adherence of Proteus mirabilis onto polymer surfaces.
AB  - AIMS: Infection of the catheterized urinary tract with Proteus mirabilis causes
      blockage of the catheter by crystalline bacterial biofilms. The aim of this work
      is to identify a surface-coating for catheters that is not vulnerable to
      colonization by Pr. mirabilis. METHODS AND RESULTS: A parallel-plate flow-cell
      and phase contrast microscopy were used to follow bacterial adhesion onto polymer
      films. Experiments with a urease-negative mutant of Pr. mirabilis suspended in
      buffer or urine, identified agarose as a polymer on which biofilm did not form.
      In tests with wild-type urease-producing cells in urine, no adhesion of cells
      onto agarose was observed for 3 h but then as the pH rose above 8.2, the surface
      rapidly became colonized by crystalline biofilm. CONCLUSIONS: In urine at pH
      below 8.0, Pr. mirabilis does not adhere to agarose-coated surfaces. When the pH
      rises above 8.2, however, aggregates of crystals and bacteria form in the urine
      and are deposited on such surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Strategies to prevent the formation of crystalline biofilms on urinary catheters
      will need to consider both the properties of the surface-coatings and the
      requirement to prevent the alkaline conditions that induce crystal formation in
      urine.

PMID- 16630002
TI  - Effect of environmental stresses on antibody-based detection of Escherichia coli
      O157:H7, Salmonella enterica serotype Enteritidis and Listeria monocytogenes.
AB  - AIMS: To study the reaction patterns of selected antibodies to Escherichia coli
      O157:H7, Salmonella enterica serotype Enteritidis and Listeria monocytogenes
      cells exposed to various environmental stresses. METHODS AND RESULTS: Escherichia
      coli O157:H7, Salmonella Enteritidis and L. monocytogenes cells subjected to
      different environmental stress of temperatures (4 and 45 degrees C), NaCl (5.5%),
      oxidative stress (15 mmol(-1) H2O2), acidic pH (5.5) and ethanol (5%) for 3 h
      (short-term stress) or for 5 days (long-term stress) were analysed by ELISA and
      Western blotting. The ELISA results indicated that most stresses caused 12-16%
      reductions in reaction for anti-E. coli O157:H7 and 20-48% reductions for anti
      Salmonella polyclonal antibodies during short-term stress, whereas the most
      stresses exhibited enhanced reaction (44-100% increase) with the anti-L.
      monocytogenes polyclonal antibody. During long-term stress exposure to combined
      stress conditions of pH 5.5, 3.5% NaCl at 12 degrees C or at 4 degrees C,
      antibody reactions to the three pathogens were highly variable with the combined
      stress at 4 degrees C showing the most reductions (8-40%). Likewise, there were
      about 18-59% reductions in antibody reactions with pathogens when cultured in
      hotdog samples with the combined stress conditions. Western blot analyses of
      crude cell surface antigens from both short- and long-term stressed cells
      revealed that the changes in antibody reactions observed in ELISA were either
      because of repression, expression or possible denaturation of antigens on the
      surface of cells. CONCLUSIONS: Overall, the antibody reactions were significantly
      reduced in pathogens exposed to both short- and long-term environmental stresses
      in culture medium or in meat sample because of expression, repression or
      denaturation of specific antigens in cells. SIGNIFICANCE AND IMPACT OF THE STUDY:
      In order to ensure the reliable detection of foodborne pathogens using antibody
      based methods, the influence of stress on antibody reactions should be thoroughly
      examined and understood first as the physiological activities in cells are often
      altered in response to a stress.

PMID- 16630004
TI  - Optimization of the components concentrations of the lactoperoxidase system by
      RSM.
AB  - AIMS: The aim of this work was to use response surface methodology (RSM)
      approach, a statistical mathematical tool, to model effects and interactions of
      glucose oxidase (GOD), glucose, lactoperoxidase (LPO) and pH-values on the
      thiocyanate (SCN-) peroxidation, to determine the best concentrations of
      lactoperoxidase system (LP-s) components in order to obtain maximal SCN-
      peroxidation and so to enhance the LP-s antibacterial effects. METHODS AND
      RESULTS: Experimental design using RSM was used for modelling effects and
      interactions of GOD (28.5-142.5 IU l(-1)), glucose (0.55-11.11 mmol l(-1)), LPO
      (0-6284 IU l(-1)) concentrations, and pH-values (6.0-7.4) on thiocyanate
      peroxidation. A fixed SCN- concentration of 0.5 mmol l(-1) was used. Experiments
      were carried out at 4 or at 25 degrees C in 0.1 mol l(-1) phosphate buffer.
      Optimized concentrations for both temperatures (4 and 25 degrees C) were quite
      similar and were 85.5 IU l(-1) for GOD, 8 mmol l(-1) for glucose and 3927.5 IU l(
      1) for LPO at an initial pH-value of 6.5. SCN- peroxidation was more efficient at
      25 than at 4 degrees C. At 4 degrees C, no interaction between factors occurred.
      At 25 degrees C, thiocyanate peroxidation was affected by GOD/glucose, GOD/pH and
      LPO/pH. Thiocyanate peroxidation was mainly increased by glucose and LPO factors.
      The optimized system had a bacteriostatic effect on Listeria monocytogenes CIP
      82110(T) and a strong bactericidal effect on Pseudomonas fluorescens CIP 6913(T).
      CONCLUSIONS: Appropriate combinations of LPO, GOD, glucose concentrations and pH
      values allowed maximal thiocyanate peroxidation and enhanced the antibacterial
      effect of the LP-s. SIGNIFICANCE AND IMPACT OF THE STUDY: This optimization by
      RSM approach allowed a better understanding of the LP-s functioning, the
      description of the component impacts on the SCN- peroxidation, and the
      observation of different interactions between the factors. The antimicrobial
      efficiency of LP-s can be enhanced by better concentration ratios of the LP-s
      components.

PMID- 16630005
TI  - Increasing glycolytic flux in Torulopsis glabrata by redirecting ATP production
      from oxidative phosphorylation to substrate-level phosphorylation.
AB  - AIMS: This study aimed at further increasing the pyruvate productivity of a multi
      vitamin auxotrophic yeast Torulopsis glabrata by redirecting ATP production from
      oxidative phosphorylation to substrate-level phosphorylation. METHODS AND
      RESULTS: We examined two strategies to decrease the activity of F0F1-ATPase. The
      strategies were to inhibit F0F1-ATPase activity by addition of oligomycin, or to
      disrupt F0F1-ATPase by screening neomycin-resistant mutant. The addition of 0.05
      mmol l(-1) oligomycin to the culture broth of T. glabrata CCTCC M202019 resulted
      in a significantly decreased intracellular ATP level (35.7%) and a significantly
      increased glucose consumption rate (49.7%). A neomycin-resistant mutant N07 was
      screened and selected after nitrosoguanidine mutagenesis of the parent strain T.
      glabrata CCTCC M202019. Compared with the parent strain, the F0F1-ATPase activity
      of the mutant N07 decreased about 65%. As a consequence, intracellular ATP level
      of the mutant N07 decreased by 24%, which resulted in a decreased growth rate and
      growth yield. As expected, glucose consumption rate and pyruvate productivity of
      the mutant N07 increased by 34% and 42.9%, respectively. Consistently, the
      activities of key glycolytic enzymes of the mutant N07, including
      phosphofructokinase, pyruvate kinase and glyceraldehyde-3-phosphate
      dehydrogenase, increased by 63.7%, 28.8% and 14.4%, respectively. In addition,
      activities of the key enzymes involved in electron transfer chain of the mutant
      N07 also increased. CONCLUSIONS: Impaired oxidative phosphorylation in T.
      glabrata leads to a decreased intracellular ATP production, thereby increasing
      the glycolytic flux. SIGNIFICANCE AND IMPACT OF THE STUDY: The strategy of
      redirecting ATP production from oxidative phosphorylation to substrate-level
      phosphorylation provides an alternative approach to enhance the glycolytic flux
      in eukaryotic micro-organisms.

PMID- 16630006
TI  - Variation in resistance of natural isolates of Staphylococcus aureus to heat,
      pulsed electric field and ultrasound under pressure.
AB  - AIMS: To study and compare the resistance of 15 Staphylococcus aureus isolates to
      heat, pulsed electric field (PEF) and ultrasound (UW) under pressure
      (manosonication, MS). METHODS AND RESULTS: Survival curves to heat (58 degrees
      C), to PEF (22 kV cm(-1), 2 micros square wave pulses) and to UW under pressure
      (117 microm, 20 kHz, 200 kPa) were obtained and inactivation parameters (decimal
      reduction times for heat and UW under pressure, and b-values for PEF) were
      calculated. A wide resistance variation to heat treatment, but not to PEF and MS,
      was observed amongst the 15 strains. CONCLUSIONS: There was no relationship
      between the resistances to the three physical agents studied. Staphylococcus
      aureus was relatively resistant to MS but sensitive to PEF. Heat resistance
      varied with strain and was positively correlated to carotenoid pigment content.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Results would help in defining safe food
      preservation processes. Care should be taken to choose the most adequate strain
      of S. aureus to model food preservation processing.

PMID- 16630007
TI  - Persistence and efficacy of Beauveria brongniartii strains applied as biocontrol
      agents against Melolontha melolontha in the Valley of Aosta (northwest Italy).
AB  - AIMS: To monitor and select genetically characterized strains of Beauveria
      brongniartii to be used as microbiological control agents against Melolontha
      melolontha in different climatic conditions of the Valley of Aosta (northwest
      Italy). METHODS AND RESULTS: Molecular random amplified polymorphic DNA markers
      allowed monitoring of five B. brongniartii strains (C2, F, K2, N3 and W2) in
      field trials. Ten sites were chosen at Jovencan, Saint-Pierre and Quart areas,
      where a mixture of the five strains colonizing rye kernels was applied to the
      soil of each M. melolontha infested site. Growth, persistence and virulence on M.
      melolontha larvae of five fungal strains were evaluated in two subsequent 24
      month studies. Beauveria brongniartii grew best at the Jovencan sites. Not only
      did strain F persist better than the other strains in most soil samples but it
      was also the most virulent strain. Strain F was isolated the most frequently from
      infected M. melolontha larvae recovered from the test sites. A general decrease
      in the larvae rate was detected in the test field soil. CONCLUSIONS: Strain F of
      B. brongniartii was better than other strains in growth, persistence and
      virulence against M. melolontha larvae in the test site soil. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Results obtained from preliminary field trials support the
      use of strain F as a biological control agent against M. melolontha in the Valley
      of Aosta even if further targeted studies are still necessary.

PMID- 16630008
TI  - Role of nucleotide excision repair and photoreactivation in the solar UVB
      radiation survival of Pseudomonas syringae pv. syringae B728a.
AB  - AIMS: To assess the role of DNA repair and photoreactivation in the solar
      radiation survival of the plant pathogen and leaf surface epiphyte Pseudomonas
      syringae pv. syringae (Pss). METHODS AND RESULTS: Mutants of Pss B728a, with
      insertional mutations within the nucleotide excision repair gene uvrA, photolyase
      gene phr, or uvrA phr double mutants, were constructed to examine the importance
      of individual repair mechanisms in solar UV radiation (UVR) survival. The
      survival of either the uvrA mutant or the phr mutant was reduced by approx. 10(2)
      fold following exposure to a dose of 4.5 kJ m(-2) solar UVB (290-320 nm
      wavelengths) while the uvrA phr double mutant was reduced >10(6)-fold by the same
      dose. We constructed a transcriptional fusion between the Pss recA promoter and
      gfp to examine the induction of the SOS response in wild-type and mutant strains.
      Initiation of the recA mediated SOS response was more rapid and peaked at higher
      levels in mutant strains suggesting both increased DNA damage in mutant strains
      and also that photoreactivation and nucleotide excision repair remove DNA damage
      as it is incurred which is reflected in a delay of recA expression. Visualization
      of expression of B728a cells containing the recA::gfp reporter on UVB-irradiated
      bean leaves highlighted the movement of cells to intercellular spaces over time
      and that SOS induction was detectable when leaves were irradiated 48 h following
      leaf inoculation. CONCLUSIONS: This study indicated that solar UVB is detrimental
      to Pss B728a, DNA repair mechanisms play an important role in strain survival and
      expression of the SOS regulon on leaf surfaces contributes to survival of UVR
      exposed cells during plant colonization. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This work links previous laboratory-based UVR analyses with solar UVB dose
      response analyses and highlights the role of photoreactivation in delaying
      induction of the SOS response following solar irradiation. Knowledge of
      population dynamics following direct solar irradiation will enhance our
      understanding of the biology of Pss in the phyllosphere.

PMID- 16630009
TI  - Characterization of Erwinia amylovora strains from different host plants using
      repetitive-sequences PCR analysis, and restriction fragment length polymorphism
      and short-sequence DNA repeats of plasmid pEA29.
AB  - AIMS: The three main aims of the study were the assessment of the genetic
      relationship between a deviating Erwinia amylovora strain isolated from
      Amelanchier sp. (Maloideae) grown in Canada and other strains from Maloideae and
      Rosoideae, the investigation of the variability of the PstI fragment of the pEA29
      plasmid using restriction fragment length polymorphism (RFLP) analysis and the
      determination of the number of short-sequence DNA repeats (SSR) by DNA sequence
      analysis in representative strains. METHODS AND RESULTS: Ninety-three strains
      obtained from 12 plant genera and different geographical locations were examined
      by repetitive-sequences PCR using Enterobacterial Repetitive Intergenic
      Consensus, BOX and Repetitive Extragenic Palindromic primer sets. Upon the
      unweighted pair group method with arithmetic mean analysis, a deviating strain
      from Amelanchier sp. was analysed using amplified ribosomal DNA restriction
      analysis (ARDRA) analysis and the sequencing of the 16S rDNA gene. This strain
      showed 99% similarity to other E. amylovora strains in the 16S gene and the same
      banding pattern with ARDRA. The RFLP analysis of pEA29 plasmid using MspI and
      Sau3A restriction enzymes showed a higher variability than that previously
      observed and no clear-cut grouping of the strains was possible. The number of SSR
      units reiterated two to 12 times. The strains obtained from pear orchards showing
      for the first time symptoms of fire blight had a low number of SSR units.
      CONCLUSIONS: The strains from Maloideae exhibit a wider genetic variability than
      previously thought. The RFLP analysis of a fragment of the pEA29 plasmid would
      not seem a reliable method for typing E. amylovora strains. A low number of SSR
      units was observed with first epidemics of fire blight. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The current detection techniques are mainly based on the genetic
      similarities observed within the strains from the cultivated tree-fruit crops.
      For a more reliable detection of the fire blight pathogen also in wild and
      ornamentals Rosaceous plants the genetic features of deviating E. amylovora
      strains have to be studied in detail.

PMID- 16630010
TI  - Sensitive detection of Mycobacterium avium subsp. paratuberculosis in bovine
      semen by real-time PCR.
AB  - AIMS: To develop a fast and sensitive protocol for detection of Mycobacterium
      avium subsp. paratuberculosis (MAP) in bovine semen and to make a critical
      evaluation of the analytical sensitivity. METHODS AND RESULTS: Processed semen
      was spiked with known amounts of MAP. Semen from different bulls as well as semen
      of different dilutions was tested. The samples were treated with lysing agents
      and beadbeating and the DNA was extracted with phenol and chloroform. Real-time
      PCR with a fluorescent probe targeting the insertion element IS900 detected as
      few as 10 organisms per sample of 100 mul semen. PCR-inhibition was monitored by
      inclusion of an internal control. Pre-treatment with immunomagnetic separation
      was also evaluated, but was not shown to improve the overall sensitivity.
      CONCLUSIONS: Real-time PCR is a sensitive method for detection of MAP in bovine
      semen. Lysis by mechanical disruption followed by phenol and chloroform
      extraction efficiently isolated DNA and removed PCR-inhibitors. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The high sensitivity of the applied method allows reliable
      testing of bovine semen used for artificial insemination to prevent the spread of
      Johne's disease, caused by MAP.

PMID- 16630011
TI  - Antimicrobial resistance in bacteria isolated from aquaculture sources in
      Australia.
AB  - AIMS: To carry out a preliminary assessment of the occurrence of resistance to
      antimicrobials in bacteria that has been isolated from a variety of aquaculture
      species and environments in Australia. METHOD AND RESULTS: A total of 100 Gram
      negative (Vibrio spp. and Aeromonas spp. predominantly) and four Gram-positive
      bacteria isolated from farmed fish, crustaceans and water from crab larval
      rearing tanks were obtained from diagnostic laboratories from different parts of
      Australia. All the isolates were tested for sensitivity to 19 antibiotics and
      Minimal Inhibitory Concentrations were determined by the agar dilution method.
      Plasmid DNA was isolated by the alkali lysis method. Resistance to ampicillin,
      amoxycillin, cephalexin and erythromycin was widespread; resistance to
      oxytetracycline, tetracycline, nalidixic acid and sulfonamides was common but
      resistance to chloramphenicol, florfenicol, ceftiofur, cephalothin, cefoperazone,
      oxolinic acid, gentamicin, kanamycin and trimethoprim was less common. All
      strains were susceptible to ciprofloxacin. Multiple resistance was also observed
      and 74.4% of resistant isolates had between one and ten plasmids with sizes
      ranging 2-51 kbp. CONCLUSIONS: No antibiotics are registered for use in
      aquaculture in Australia but these results suggest that there has been
      significant off-label use. SIGNIFICANCE AND IMPACT OF STUDY: Transfer of
      antibiotic resistant bacteria to humans via the food chain is a significant
      health concern. In comparison with studies on terrestrial food producing animals,
      there are fewer studies on antibiotic resistance in bacteria from aquaculture
      enterprises and this study provides further support to the view that there is the
      risk of transfer of resistant bacteria to humans from consumption of aquaculture
      products. From the Australian perspective, although there are no products
      registered for use in aquaculture, antimicrobial resistance is present in
      isolates from aquaculture and aquaculture environments.

PMID- 16630012
TI  - Bioconversion of grape must into modulated gluconic acid production by
      Aspergillus niger ORS-4.410.
AB  - AIMS: Analysis of regulators for modulated gluconic acid production under surface
      fermentation (SF) condition using grape must as the cheap carbohydrate source, by
      mutant Aspergillus niger ORS-4.410. Replacement of conventional fermentation
      condition by solid-state surface fermentation (SSF) for semi-continuous
      production of gluconic acid by pseudo-immobilization of A. niger ORS-4.410.
      METHODS AND RESULTS: Grape must after rectification was utilized for gluconic
      acid production in batch fermentation in SF and SSF processes using mutant strain
      of A. niger ORS-4.410. Use of rectified grape must led to the improved levels of
      gluconic acid production (80-85 g l(-1)) in the fermentation medium containing
      0.075% (NH4)2HPO4; 0.1% KH2PO4 and 0.015% MgSO4.7H2O at an initial pH 6.6 (+/
      0.1) under surface fermentation. Gluconic acid production was modulated by
      incorporating the 2% soybean oil, 2% starch and 1% H2O2 in fermentation medium at
      continuously high aeration rate (2.0 l min(-1)). Interestingly, 95.8% yield of
      gluconic acid was obtained when A. niger ORS-4.410 was pseudo-immobilized on
      cellulose fibres (bagasse) under SSF. Four consecutive fermentation cycles were
      achieved with a conversion rate of 0.752-0.804 g g(-1) of substrate into gluconic
      acid under SSF. CONCLUSIONS: Use of additives modulated the gluconic acid
      production under SF condition. Semi-continuous production of gluconic acid was
      achieved with pseudo-immobilized mycelia of A. niger ORS-4.410 having a promising
      yield (95.8%) under SSF condition. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      bioconversion of grape must into modulated gluconic acid production under SSF
      conditions can further be employed in fermentation industries by replacing the
      conventional carbohydrate sources and expensive, energy consuming fermentation
      processes.

PMID- 16630013
TI  - Individual microflora beget unique oral microcosms.
AB  - AIMS: To examine the efficacy of the multiple Sorbarod device (MSD) for the
      reproduction of inter-individual variations in oral microbiotas. The MSD supports
      sessile growth on parallel cellulose filters, perfused with artificial saliva.
      This enables biofilms (BF) to be grown and sampled, together with released cells
      in eluted medium (perfusates, PAs). METHODS AND RESULTS: Two sets of triplicate
      MSDs were established. One set was inoculated using fresh saliva from three
      separate volunteers; the second set was inoculated from one saliva donor. Both
      were incubated in an anaerobic cabinet. BF and PA were analysed at 24-h intervals
      by PCR-denaturing gradient gel electrophoresis (DGGE) of 16S rDNA. Hierarchical
      dendrograms were constructed in order to sort community fingerprints over time,
      based on community relatedness. The MSD supported complex oral communities, as
      evidenced by DGGE (>20 distinct DGGE bands) and confocal scanning laser
      microscopy. DGGE band sequencing revealed bacteriological diversity and a high
      incidence of anaerobic species, including Prevotella sp. Dendrograms demonstrated
      marked inter-individual variation in the relative species abundance within
      salivary inocula from different volunteers (DV) and each associated MSD (all
      >45%, majority c. 85% concordance). Less variation was shown between triplicate
      models established using saliva from a single volunteer (SV) (all >58%; majority
      c. 95% concordance). PAs clustered together with the associated biofilms and
      inocula in the majority of cases for the DV MSDs whilst SV MSD community profiles
      clustered between replicate MSDs. CONCLUSIONS: Data indicate that marked inter
      individual variations in human salivary composition can be partially replicated
      in individualized MSD microcosms. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study demonstrates the in vitro reproduction of individual oral microbiotas and
      suggests that taking inter-individual variability into account will increase the
      relevance of microcosm studies.

PMID- 16630014
TI  - Effects of chronic triclosan exposure upon the antimicrobial susceptibility of 40
      ex-situ environmental and human isolates.
AB  - BACKGROUND: Triclosan (TCS) exposure of Escherichia coli selects for tolerant
      clones, mutated in their enoyl-acyl carrier protein reductase (FabI). It has been
      inferred that this phenomenon is widespread amongst bacterial genera and might be
      associated with resistance to third party agents. METHODS: Ex-situ, low passage
      isolates of enteric, human axilla, human oral origin and bacteria isolated from a
      domestic drain, together with selected type cultures were exposed to escalating
      concentrations of TCS over 10 passages using a gradient plate technique. One
      fresh faecal isolate of E. coli was included as a positive control. TCS
      susceptibility was determined for all strains before and after exposure, whilst
      enteric isolates were additionally assessed for susceptibility towards
      chlorhexidine, tetracycline, chloramphenicol, nalidixic acid and ciprofloxacin,
      and the oral isolates towards chlorhexidine, tetracycline and metronidazole.
      RESULTS: Triclosan exposure of E. coli markedly decreased TCS susceptibility. TCS
      susceptibility also decreased for Klebsiella oxytoca, Aranicola proteolyticus and
      Stenotrophomonas maltophilia. Susceptibility of the remaining 35 strains to TCS
      and the other test agents remained unchanged. CONCLUSIONS: These data suggest
      that selection for high level resistance by TCS exposure is not widespread and
      appears to be confined to certain enteric bacteria, especially E. coli. Change in
      TCS susceptibility did not affect susceptibility towards chemically unrelated
      antimicrobials. SIGNIFICANCE AND IMPACT: Acquired high-level TCS resistance is
      not a widespread phenomenon.

PMID- 16630015
TI  - Comparison of a monoclonal antibody-based capture/enrichment sandwich enzyme
      linked immunosorbent assay with immunomagnetic bead separation for the detection
      of attachment effacement Escherichia coli O26 strains from cattle faeces.
AB  - AIMS: A monoclonal antibody (Mab 2F3)-based sandwich enzyme linked immunosorbent
      assay (sELISA) format for the detection of Escherichia coli O26 that improves the
      sensitivity of the assay by combining enrichment with the capture stage has been
      developed. Culture of the enriched contents of wells before completion of the
      sELISA was compared with immunomagnetic bead separation (IMS) as a means of
      specific isolation of the target organism. METHODS AND RESULTS: Bovine faecal
      samples, c. 10% in buffered peptone water (BPW), were pre-enriched for 6 h before
      testing by capture/enrichment sELISA and by IMS. The sELISA consisted of a 1-2 h
      capture stage followed by addition of BPW to the wells and an overnight
      enrichment stage before completion of the assay. The capture/enrichment stage of
      the assay was repeated a second time on the enriched contents removed from the
      wells before completion of the first sELISA. From 204 cattle faeces samples, 30x
      O26 strains [20x attachment effacement Escherichia coli (AEEC) and 10x non-AEEC]
      were isolated from the enriched wells of the sELISA, in comparison with 11 (9x
      AEEC and 2x non-AEEC) that were isolated by IMS. Examination of the use of
      enterohaemolysin activity and rhamnose utilization on 1% rhamnose McConkey's
      (RMAC) agar with or without cefixime and potassium tellurite demonstrated that
      the selection based on enterohaemolysin production and growth on RMAC with
      cefixime and potassium tellurite would largely differentiate the AEEC strains
      from the non-AEEC strains. CONCLUSIONS: The capture/enrichment sELISA protocol
      used compared favourably with the IMS for the isolation of E. coli O26 from
      faeces samples. The ELISA optical density readings obtained in the procedure were
      used as a screening indicator for selection of samples for further culture
      examination, and the selective culture methods examined to assist strain
      isolation did have potential. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      capture/enrichment format of an Mab-based sELISA protocol has the potential to
      provide a suitable screening assay for the specific detection of pathogenic
      strains from mixed culture samples like faeces.

PMID- 16630016
TI  - Detection of Magnaporthe grisea in infested rice seeds using polymerase chain
      reaction.
AB  - AIM: To develop a diagnostic assay based on polymerase chain reaction for the
      detection of Magnaporthe grisea from infested rice seeds. METHODS AND RESULTS:
      Primers were designed based on the nucleotide sequence of the mif 23, an
      infection-specific gene of M. grisea. The primers amplified target DNA from
      genetically and geographically diverse isolates of the pathogen. The lowest
      concentration of template DNA that led to amplification was 20 rhog. No PCR
      product was detected when DNA from other fungi was used, indicating the
      specificity of the primers. With this PCR based seed assay, M. grisea was
      detected in rice seedlots with infestation rates as low as 0.2%. CONCLUSION: The
      PCR detection of M. grisea is simple, rapid, specific, sensitive and suitable for
      the routine detection of the pathogen in infested seeds. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Introduction of the blast fungus into new areas where it has not
      been previously recorded could be avoided by the detection of infested seedlots.
      A PCR-based seed assay could facilitate risk assessment of naturally infested
      rice seeds; help design management programs and optimize fungicide use.

PMID- 16630017
TI  - Chlorine spot treatment of flooded tube wells, an efficacy trial.
AB  - AIMS: To evaluate the water quality of recently flooded tube wells in Bangladesh
      and the effect of spot chlorination on improving bacteriological quality. METHODS
      AND RESULTS: The study team identified and tested water samples from 127 tube
      wells that were flooded within the preceding 4 weeks. Twenty-six of the tube
      wells with the highest concentration of thermotolerant coliform bacteria were
      randomly assigned to spot chlorination vs control. On initial screening, water
      samples from 56 recently inundated tube wells (44%) were contaminated with
      thermotolerant coliforms. Among the 13 wells randomized to chlorination, there
      was no change in the proportion of water samples that had no detectable
      thermotolerant coliform bacteria immediately before chlorine treatment (n = 4,
      23%) and 60 min following chlorine treatment (n = 4, 23%). Similarly, there was
      no difference in the proportion of water samples that had no detectable
      thermotolerant coliforms between chlorine spot treated and control tube wells 7
      18 days later (31 vs 23%P = 0.66). CONCLUSIONS: Spot chlorine treatment of
      inundated tube wells in Bangladesh three to 6 weeks after the flooding did not
      improve drinking water quality. SIGNIFICANCE AND IMPACT OF THE STUDY: Unless
      modified methods improve effectiveness, resources should not be spent promoting
      spot chlorination of flooded tube wells.

PMID- 16630018
TI  - Regulatory T cells in human disease and their potential for therapeutic
      manipulation.
AB  - Regulatory T cells are proposed to play a central role in the maintenance of
      immunological tolerance in the periphery, and studies in many animal models
      demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a
      recent meeting [Clinical Application of Regulatory T Cells, 7-8 April 2005,
      Horsham, UK, organized by the authors of this review, in collaboration with the
      British Society for Immunology and Novartis] evidence was discussed that certain
      human autoimmune, infectious and allergic diseases are associated with impaired
      regulatory T-cell function. In contrast, evidence from several human cancer
      studies and some infections indicates that regulatory T cells may impair the
      development of protective immunity. Importantly, certain therapies, both those
      that act non-specifically to reduce inflammation and antigen-specific
      immunotherapies, may induce or enhance regulatory T-cell function. The purpose of
      this review was to summarize current knowledge on regulatory T-cell function in
      human disease, and to assess critically how this can be tailored to suit the
      therapeutic manipulation of immunity.

PMID- 16630019
TI  - Fibrosis in heart disease: understanding the role of transforming growth factor
      beta in cardiomyopathy, valvular disease and arrhythmia.
AB  - The importance of fibrosis in organ pathology and dysfunction appears to be
      increasingly relevant to a variety of distinct diseases. In particular, a number
      of different cardiac pathologies seem to be caused by a common fibrotic process.
      Within the heart, this fibrosis is thought to be partially mediated by
      transforming growth factor-beta1 (TGF-beta1), a potent stimulator of collagen
      producing cardiac fibroblasts. Previously, TGF-beta1 had been implicated solely
      as a modulator of the myocardial remodelling seen after infarction. However,
      recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies
      are all associated with raised levels of TGF-beta1. In fact, the pathogenic
      effects of TGF-beta1 have now been suggested to play a major role in valvular
      disease and arrhythmia, particularly atrial fibrillation. Thus far, medical
      therapy targeting TGF-beta1 has shown promise in a multitude of heart diseases.
      These therapies provide great hope, not only for treatment of symptoms but also
      for prevention of cardiac pathology as well. As is stated in the introduction,
      most reviews have focused on the effects of cytokines in remodelling after
      myocardial infarction. This article attempts to underline the significance of TGF
      beta1 not only in the post-ischaemic setting, but also in dilated and
      hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on
      atrial fibrillation). It also aims to show that TGF-beta1 is an appropriate
      target for therapy in a variety of cardiovascular diseases.

PMID- 16630020
TI  - Large HIV-specific CD8 cytotoxic T-lymphocyte (CTL) clones reduce their overall
      size but maintain high frequencies of memory CTL following highly active
      antiretroviral therapy.
AB  - Cytotoxic T-lymphocytes (CTL) play an important role in the control of human
      immunodeficiency virus (HIV) and of human cytomegalovirus (HCMV) infection.
      Following highly active antiretroviral therapy (HAART), most studies have
      demonstrated a decline in the frequency of HIV-specific CTL. We analysed the
      effect of HAART on the size, phenotype and function of individual HIV- and HCMV
      specific CTL clones, using clonotypic oligonucleotide probing specific for the T
      cell receptor (TCR) beta-chain hypervariable sequence of defined immunodominant
      CTL clones specific for peptides of HIV or HCMV, and quantified the limiting
      dilution analysis frequencies of CTL precursors (CTLp) specific for the same
      viral peptides. We found that the clonal composition of CD8+ T cells specific for
      HIV gag and env epitopes was highly focused and did not change after HAART.
      Following HAART, there was progressive contraction of HIV-specific CD8+ clones,
      especially in the CD28- CD27- subpopulation--the remaining cells of contracting
      HIV-specific clones were predominantly CD28- CD27+ CD45RO(hi). We observed
      maintenance of strong functional HIV-specific CD8+ T-cell responses in limiting
      dilution analysis following HAART, indicating preferential loss of HIV-specific
      cells that have reduced cloning efficiency in vitro. Following HAART, we also
      observed selective expansion of HCMV-specific CD8+ clones. Most HCMV-specific
      CD8+ clones were predominantly CD28- CD27+/- CD45RA(hi) following HAART. In one
      subject, a Vbeta6.4+ clone specific for HCMV pp65 selectively expanded following
      HAART, without expansion of two other Vbeta6.4+ clones, indicating that
      individual clonotypes specific for the same peptide can show different kinetics
      and phenotypes in response to antiretroviral therapy.

PMID- 16630021
TI  - Interferon-alphabeta mediates partial control of early pulmonary Mycobacterium
      bovis bacillus Calmette-Guerin infection.
AB  - The role of type I interferon (IFN-alphabeta) in modulating innate or adaptive
      immune responses against mycobacterial infection in the lung is unclear. In this
      study we investigated the susceptibility of IFN-alphabeta-receptor-deficient (IFN
      alphabetaR-/-) mice to pulmonary infection with aerosolized Mycobacterium bovis
      bacillus Calmette-Guerin (BCG). During early infection (2-3 weeks), enhanced
      growth of BCG was measured in the lungs of IFN-alphabetaR-/- mice compared to
      wild-type mice. However, during late infection the burden of BCG was similar in
      the lungs of IFN-alphabetaR-/- and wild-type mice. Although control of BCG growth
      was delayed, recruitment and activation of T and natural killer cells, production
      of IFN-gamma, and cytokine expression were all similar in wild-type and IFN
      alphabetaR-/- mice. However, decreased expression of nitric oxide in
      bronchoalveolar lavage fluids from IFN-alphabetaR-/- mice correlated with
      enhanced growth of BCG. Bone marrow-derived macrophages from IFN-alphabetaR-/-
      mice also produced less nitric oxide following infection with BCG in vitro. These
      findings suggest that IFN-alphabeta contributes to innate immunity to pulmonary
      mycobacterial infection by augmenting production of nitric oxide.

PMID- 16630022
TI  - Identification of a major histocompatibility complex class I-restricted T-cell
      epitope in the tumour-associated antigen, 5T4.
AB  - 5T4 is a surface glycoprotein expressed on placental trophoblasts and also on a
      wide range of human carcinomas. Its highly restricted expression on normal
      tissues and broad distribution on many carcinomas make 5T4 a promising target for
      cancer immunotherapy. In the current study, we set out to investigate whether a
      5T4-specific cytotoxic T lymphocyte (CTL) repertoire exists in healthy
      individuals. CD4-depleted peripheral blood mononuclear cells (PBMCs) from blood
      donors were screened using an ex vivo interferon-gamma (IFN-gamma) enzyme-linked
      immunospot (ELISPOT) assay. A panel of overlapping peptides, spanning the full
      length of the 5T4 protein, was used as a source of antigen. In the process of
      screening, one out of 30 blood donors demonstrated a positive ex vivo IFN-gamma
      ELISPOT response to a single 5T4 peptide. A polyclonal T-cell line was derived
      from this donor by culturing PBMCs with autologous peptide-pulsed dendritic cells
      (DCs). The resulting polyclonal T-cell line and clones were tested in a 51Cr
      release assay and by ELISPOT and were shown to be peptide specific. Furthermore,
      antigen-presenting cells (APCs), infected with a viral vector expressing 5T4,
      were able to stimulate IFN-gamma production by the peptide-specific T-cell
      clones. A minimal CD8 epitope, PLADLSPFA, has been identified and found to be
      restricted through human leucocyte antigen (HLA) Cw7. Subsequently, we have
      demonstrated that HLA-Cw7-positive colorectal cancer patients vaccinated with a
      recombinant vaccinia viral vector encoding 5T4 (TroVax) are capable of mounting a
      strong IFN-gamma ELISPOT response to this novel CTL epitope. These findings have
      potential application in cancer immunotherapy in terms of subunit vaccine design
      and the monitoring of immune responses induced in patients by 5T4-based
      therapies.

PMID- 16630023
TI  - Oestradiol potentiates the suppressive function of human CD4 CD25 regulatory T
      cells by promoting their proliferation.
AB  - CD4+ CD25+ regulatory T (Treg) cells play an important role in the control of the
      immune system by suppressing the proliferation of effector cells, thereby
      preventing autoreactive, unnecessary or inconvenient responses. Recently, it has
      been shown that the number of Treg cells increases during pregnancy, a period
      with high serum levels of female sex hormones. Oestrogen replacement therapy has
      been reported to alleviate the symptoms of autoimmune diseases, yet the cellular
      and molecular mechanisms involved are not fully understood. Here, we show that
      physiological doses of oestradiol (E2) found during pregnancy, combined with
      activation through CD3/CD28 engagement, promoted the proliferation of Treg cells
      without altering their suppressive phenotype. Enhanced suppression was detected
      when Treg cells were pretreated with the hormone as well as when both cell
      subpopulations (Treg and T effector) were exposed to E2 throughout the
      experiment. Together, these data suggest that when combined with an activating
      stimulus, E2 can modulate the function of human Treg cells by regulating their
      numbers, and highlight a potential use of E2, or its analogs, to manipulate Treg
      function.

PMID- 16630024
TI  - Type I cytokine profiles of human naive and memory B lymphocytes: a potential for
      memory cells to impact polarization.
AB  - B cells bifurcating along 'type 1' or 'type 2' pathways under the influence of
      polarizing cytokines can, in turn, influence the direction of an immune response.
      Here, we compare the capacity of human B cells residing within naive and memory
      compartments to participate in type 1 polarizing responses. B-cell receptor (BCR)
      engagement provided the main signal for interleukin (IL)-12Rbeta1 expression in
      the two subsets: this was potentiated by CD154 together with interferon-gamma
      (IFN-gamma) but inhibited by IL-12. IL-12Rbeta2 could be induced on a minority of
      B cells by the same signals, and also by IFN-gamma alone. WSX-1, a receptor for
      IL-27, was expressed in both subsets with no evidence for its regulation by the
      signals studied. While neither subset was capable of secreting much IL-12 p70,
      memory B cells could produce a small amount of IL-12 p40 on CD40 ligation. Memory
      B cells also, exclusively, expressed IL-23 p19 mRNA on BCR triggering.
      Importantly, products of appropriately stimulated memory--but not naive--B cells
      were shown to promote the synthesis of IFN-gamma in uncommitted T-helper cells.
      The data indicate an equal capacity for naive and memory B cells to respond
      within a type 1 polarizing environment. Although poorly equipped for initiating
      type 1 responses, B cells--by virtue of the memory subset--reveal a capacity for
      their maintenance and amplification following T-dependent signalling.

PMID- 16630025
TI  - Role of natural interferon-producing cells and T lymphocytes in porcine monocyte
      derived dendritic cell maturation.
AB  - Maturation of dendritic cells (DC) is a key immunological process regulating
      immune responses to pathogens and vaccines, as well as tolerance and autoimmune
      processes. Consequently, the regulation of DC maturation should reflect these
      multifaceted immunological processes. In the present study, we have defined the
      role of particular cytokines, Toll-like receptor (TLR) ligands and T lymphocytes
      in the porcine monocyte-derived DC (MoDC). Interferon-alpha (IFN-alpha) alone was
      a poor inducer of MoDC maturation, but in association with tumour necrosis factor
      alpha (TNF-alpha), or TLR ligands such as lipopolysaccharide and polyinosinic
      polycytidylic acid I:C, an up-regulation of major histocompatibility complex II
      and CD80/86 expression was noted, along with reduced endocytic activity. In
      contrast, TNF-alpha alone or in combination with the TLR ligands was a poor
      inducer of DC maturation, but co-operated with T-lymphocytes in the presence of
      antigen to induce DC maturation. Natural interferon producing cells (NIPC, or
      plasmacytoid DCs) represent a danger-recognition system of the immune defences,
      and can respond to viruses not otherwise recognized as posing a danger. Indeed,
      MoDC did not respond to transmissible gastroenteritis virus (TGEV), whereas NIPC
      produced high levels of IFN-alpha and TNF-alpha after TGEV stimulation. Moreover,
      supernatants from the stimulated NIPC induced maturation in MoDCs. These matured
      MoDCs displayed an enhanced ability to present antigen to and thus stimulate T
      cells. Taken together, the present work demonstrates that maturation of MoDC not
      only results from TLR signalling, but can require co-operation with various cell
      types--principally NIPC and activated T cells--which would reflect the particular
      immunological situation.

PMID- 16630026
TI  - Molecular characterization of immunoglobulin D in mammals: immunoglobulin heavy
      constant delta genes in dogs, chimpanzees and four old world monkey species.
AB  - Antibodies are adaptor molecules that neutralize pathogens and link humoral and
      cellular defence mechanisms. Immunoglobulin D (IgD), one of the five antibody
      classes present in mammals, is expressed as an antigen receptor on naive B cells.
      The functional role that IgD plays in the immune response is still poorly
      understood, but the recent characterization of immunoglobulin heavy constant
      delta genes (IGHD) in a variety of species challenges the view that IgD is of
      minor importance and is not present in many animals. On the basis of serological
      studies, IgD appears to be expressed in the majority of mammalian species
      examined. To confirm, at the molecular level, that IgD is present in different
      species, we cloned and sequenced IGHD cDNA from dogs and five non-human primate
      species (chimpanzee, rhesus macaque, cynomolgus macaque, baboon and sooty
      mangabey). Our results show that in all six species, IgD heavy chains possess
      three immunoglobulin domains and a long hinge region encoded by two exons. Only
      the hinge region of non-human primates is similar to the human hinge region, with
      conservation of O-glycosylation sites and multiple charged residues at opposing
      ends. The preservation of IgD in primates, dogs and previously characterized
      species suggests an important functional role for IgD, possibly involving binding
      to a receptor. The high degree of similarity existing between the structural
      features of human and non-human primate IgD suggests that non-human primates are
      suitable for in vivo studies designed to define the role that IgD plays in the
      immune response.

PMID- 16630027
TI  - NKT cells play critical roles in the induction of oral tolerance by inducing
      regulatory T cells producing IL-10 and transforming growth factor beta, and by
      clonally deleting antigen-specific T cells.
AB  - Oral tolerance is the systemic unresponsiveness induced by orally administered
      proteins. To explore the roles of natural killer T (NKT) cells in oral tolerance,
      we induced oral tolerance to ovalbumin (OVA) in NKT cell-deficient mice. In CD1d
      /- mice, the induction of tolerance to orally administered high- or low-dose OVA
      was impaired. Dendritic cells (DCs) in the Peyer's patches (PPs) of CD1d-/- mice
      fed OVA showed high expression of major histocompatibility complex (MHC) class II
      and B7 molecules, whereas DCs of control mice fed OVA expressed low levels of
      these molecules. The adoptive transfer of NKT cells restored oral tolerance and
      induction of tolerogenic DCs in the PPs and spleens of CD1d-/- mice. Moreover,
      interleukin (IL)-10 and transforming growth factor (TGF)-beta1 production in
      vitro were reduced in cells from the spleen and PPs of CD1d-/- mice compared with
      those of control mice fed OVA. The numbers of OVA-specific CD4+ KJ1-26+ T cells
      were significantly reduced in the PPs and spleens of DO11.10 mice fed OVA. In
      contrast, OVA-specific CD4+ KJ1-26+ T cells were not deleted in the PPs or
      spleens of DO11.10 CD1d-/- mice. In conclusion, NKT cells were found to play an
      indispensable role in oral tolerance by inducing regulatory T cells, and clonally
      deleting antigen-specific CD4+ T cells.

PMID- 16630028
TI  - The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha
      production and epithelial cell apoptosis in acute murine colitis.
AB  - Stress-activated protein kinases (SAPKs) are activated in human inflammatory
      bowel disease (IBD). Recently it has been demonstrated that p38MAPK (mitogen
      activated protein kinase) inhibition using SB203580 is effective in reducing
      disease in both dextran sulphate sodium (DSS)-induced and 2,4,6
      trinitrobenzenesulphonic acid (TNBS)-induced murine colitides, underscoring the
      importance of this pathway in gastrointestinal inflammation. However, the
      contribution of c-Jun N-terminal kinase (JNK) in intestinal inflammation is
      unknown. Based on the known involvement of JNK in tumour necrosis factor-alpha
      (TNF-alpha) expression and in mediating the effects of oxidant stress, we
      hypothesized that JNK inhibition would also affect colitis. Our studies in mice
      with DSS-induced colitis treated with the JNK inhibitor SP600125, indicate that
      there is a significant reduction in wasting as well as a significant reduction in
      histological damage scores. Both total colonic and mesenteric lymphocyte CD3/CD28
      stimulated TNF-alpha levels were dramatically reduced under the same
      circumstances. This was associated with a reduction in JNK protein expression and
      activity, as well as a reduction in AP-1 DNA binding with SP600125.
      Interestingly, there were no apparent changes in either p38MAPK or p42/44ERKs.
      Immunofluorescence of the colon for the active form of JNK revealed a prominent
      signal arising from the infiltrating inflammatory cells. SP600125 reduced this as
      well as, specifically, macrophage infiltration. Strikingly, we also demonstrate
      reduced epithelial cell apoptosis in response to treatment with SP600125. We
      conclude that specific inhibition of JNK is beneficial in the DSS model of
      colitis, and may be of value in human IBD.

PMID- 16630029
TI  - Genetic control of immune-mediated necrosis of Mycobacterium avium granulomas.
AB  - Intravenous infection of C57BL/6 and C57BL/10 mice with low doses of a highly
      virulent strain of Mycobacterium avium (ATCC 25291) led to the development of
      granulomas that underwent necrosis. In contrast, neither BALB/c nor DBA/1 mice
      developed granuloma necrosis after such infection despite a similar course of
      mycobacterial proliferation. Studies with C57BL/10 mice congenic for the Hc locus
      revealed that an intact complement C5 gene is required for granuloma necrosis. On
      the other hand, genetic disruption of the interleukin-10 gene in BALB/c mice made
      this strain susceptible to granuloma necrosis.

PMID- 16630030
TI  - Evolutionary conservation of neuropeptide expression in the thymus of different
      species.
AB  - Evidence suggests that the immune and neuroendocrine systems cross talk by
      sharing ligands and receptors. Hormones and neuropeptides produced by the
      neuroendocrine system often modulate the function of lymphoid organs and immune
      cells. We have previously reported the intrathymic expression of somatostatin
      (SOM) in the mouse and that several neuropeptides, most notably calcitonin-gene
      related peptide (CGRP), neuropeptide Y (NPY), SOM and substance P (SP), can
      modulate thymocyte development. However, little is known about the intrathymic
      expression of these neuropeptides either in the mouse or in other species.
      Moreover, a comparative analysis of the expression of these molecules would
      highlight the evolutionary importance of intrathymic neuroendocrine interactions
      in T-cell development. We have studied the expression of different neuropeptides
      in the thymus of zebrafish, Xenopus, avians, rodent, porcine, equine and human by
      immunohistochemistry and reverse transcription-polymerase chain reaction. We
      found that CGRP, NPY, SOM, SP and vasointestinal polypeptide (VIP) are expressed
      in the thymus of all species investigated. The thymic location of many of these
      neuropeptides was conserved and appears to be within the stromal compartments.
      Interestingly, in the avian thymus the expression of CGRP, SOM and SP appears to
      change depending on the age of the tissue. These findings suggest that
      neuropeptides may play an important role in T-cell development and provide
      further evidence of cross talk between the immune and neuroendocrine systems.

PMID- 16630031
TI  - Knowledge, attitudes and health outcomes in HIV-infected travellers to the USA.
AB  - BACKGROUND: The USA bans entry to non-citizens unless they obtain a waiver visa.
      AIM: To establish how many people with HIV infection travelled to the USA,
      whether they were aware of the travel restriction, whether they travelled with a
      waiver visa and HIV inclusive medical insurance and how they managed with their
      antiretroviral medication (ARV). DESIGN: Collation of data from cross-sectional
      studies conducted independently at three different medical centres, Manchester,
      Brighton and London, using a structured self-completion questionnaire. RESULTS:
      The overall response rate was 66.6% (1113 respondents). 349 (31%) had travelled
      to the USA since testing HIV positive, of whom only 14.3% travelled with a waiver
      visa. 64% and 62% of the respondents at Manchester and Brighton were aware of the
      need of a waiver visa. 68.5% (212) were on ARV medication at the time of travel
      and, of these, 11.3% stopped their medication. Of those taking ARV medication,
      only 25% took a doctors' letter, 11.7% posted their medication in advance. Of
      those discontinuing treatment (n=27), 55.5% sought medical advice before
      stopping, 11 were on NNRTI-based regimen and one developed NNRTI-based mutation.
      Only 27% took up HIV inclusive medical insurance. Many patients reported negative
      practical and emotional experiences resulting from travel restrictions.
      CONCLUSION: The majority of HIV patients travel to the USA without the waiver
      visa, with nearly half doing so with insufficient planning and advice. A
      significant minority (11.3%) stop their medication in an unplanned manner,
      risking the development of drug resistance.

PMID- 16630032
TI  - Increased health care utilization and increased antiretroviral use in HIV
      infected individuals with mental health disorders.
AB  - OBJECTIVES: The aims of the study were to describe the prevalence and
      associations of mental health disorder (MHD) among a cohort of HIV-infected
      patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to
      examine whether antiretroviral therapy use or mortality was influenced by MHD
      (defined as a record of service provision by psychiatric services on the
      Victorian Psychiatric Case Register). It was hypothesized that HIV-positive
      individuals with MHD would have poorer treatment outcomes, reduced responses to
      highly active antiretroviral therapy (HAART) and increased mortality compared
      with those without MHD. METHODS: This is a retrospective cohort of 2981
      individuals (73% of the Victorian population diagnosed with HIV infection)
      captured on an HIV database which was electronically matched with the public
      Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system
      psychiatry service provision). The prevalence, dates and recorded specifics of
      mental health disorders at the time of the electronic match on 1 June 2000 are
      described. The association with recorded MHD, gender, age, AIDS illness, HIV
      exposure category, duration and type of antiviral therapy, treatment era (prior
      to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and
      mortality at 1 September 2001 was assessed. RESULTS: Five hundred and twenty-five
      individuals (17.6% of the Victorian HIV-positive population) were recorded with
      MHD, most frequently coded as attributable to substance dependence/abuse or
      affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed
      after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis.
      Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for
      both psychiatric and nonpsychiatric illness were more frequent in those with MHD
      (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of
      antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with
      MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4
      cell count and antiretroviral therapy, survival was not affected by MHD.
      CONCLUSIONS: MHD is frequent in this population with HIV infection and is
      associated with increased healthcare utilization but not with reduced survival.

PMID- 16630033
TI  - Intrathoracic fat in HIV-infected patients.
AB  - BACKGROUND: The impact of HIV infection or antiretroviral therapy on the
      intrathoracic fat compartment is unknown. METHODS: Consecutive clinically stable
      HIV-infected adult patients, irrespective of exposure to antiretroviral therapy,
      and non-HIV-infected healthy volunteers, both without clinical evidence of body
      fat changes consistent with lipodystrophy and adjusted for age, gender and body
      mass index, were recruited for this study. Thoracic and abdominal fat was
      assessed by computed tomography and compared between patients and controls.
      RESULTS: There were nine women (33%) and 18 men (67%) in each group. Nineteen
      patients (70%) had been taking antiretrovirals for a median of 8 months
      (interquartile range: 6-11). Among the HIV-infected patients, intrathoracic fat
      (median; interquartile range) did not differ significantly between treated (6.7
      cm(2); 4.5-8.3 cm(2)) and untreated (6.9 cm(2); 5.7-10.9 cm(2)) individuals
      (P=0.288). However, intrathoracic fat content (median; interquartile range) was
      higher in HIV-infected patients (6.8 cm(2); 5.6-10.5 cm(2)) than in controls (5.6
      cm(2); 3.9-6.7 cm(2)) (P=0.025). Intrathoracic fat was positively correlated with
      intra-abdominal fat both in patients (rho=0.6, P=0.002) and in controls (rho=0.7,
      P=0.004). CONCLUSION: In HIV-infected adults without clinical evidence of
      lipodystrophy, intrathoracic fat content was higher than in healthy persons and
      positively correlated with intra-abdominal fat content.

PMID- 16630034
TI  - The use of the Framingham equation to predict myocardial infarctions in HIV
      infected patients: comparison with observed events in the D:A:D Study.
AB  - BACKGROUND: The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs)
      Study, a prospective observational study on a cohort of 23 468 patients with HIV
      infection, indicated that the incidence of myocardial infarction (MI) increased
      by 26% per year of exposure to combination antiretroviral treatment (CART).
      However, it remains unclear whether the observed increase in the rate of MI in
      this population can be attributed to changes in conventional cardiovascular risk
      factors. OBJECTIVE: To compare the number of MIs observed among participants in
      the D:A:D Study with the number predicted by assuming that conventional
      cardiovascular risk equations apply to patients with HIV infection. METHODS: The
      Framingham equation, a conventional cardiovascular risk algorithm, was applied to
      individual patient data in the D:A:D Study to predict rates of MI by duration of
      CART. A series of sensitivity analyses were performed to assess the effect of
      model and data assumptions. Predictions were extrapolated to provide 10-year risk
      estimates, and various scenarios were modelled to assess the expected effect of
      different interventions. RESULTS: In patients receiving CART, the observed
      numbers of MIs during D:A:D follow up were similar to or somewhat higher than
      predicted numbers: 9 observed vs 5.5 events predicted, 14 vs 9.8, 22 vs 14.9, 31
      vs 23.2 and 47 vs 37.0 for<1 year, 1-2 years, 2-3 years, 3-4 years and >4 years
      CART exposure, respectively. In patients who had not received CART, the observed
      number of MIs was fewer than predicted (3 observed vs 7.6 predicted). Nine per
      cent of the study population have a predicted 10-year risk of MI above 10%, a
      level usually associated with initiation of intervention on risk factors.
      CONCLUSIONS: A consistent feature of all analyses was that observed and predicted
      rates of MI increased in a parallel fashion with increased CART duration,
      suggesting that the observed increase in risk of MI may at least in part be
      explained by CART-induced changes in conventional risk factors. These findings
      provide guidance in terms of choosing lifestyle or therapeutic interventions to
      decrease those risk factors in much the same way as in persons without HIV
      infection.

PMID- 16630035
TI  - HIV testing practices in Jamaica.
AB  - OBJECTIVES: Prevention programmes often promote HIV testing as one possible
      strategy for combating the spread of the disease. The objectives of the present
      study were to examine levels of HIV testing practices in a large sample of
      Jamaicans and the relationships among HIV testing, sociodemographic variables and
      HIV-related behaviours. METHODS: A total of 1800 persons, aged 15-49 years, were
      surveyed between May and August 2004 using a household-level, interviewer
      administered questionnaire. The questionnaire included HIV-related knowledge,
      attitudinal and behavioural items. For the present analyses, data from 1558
      sexually experienced persons were examined. RESULTS: Approximately 38% of the
      sexually experienced sample reported a history of HIV testing. Hierarchical
      logistic regression analyses revealed that adults, females, persons with post
      high school education and married persons were more likely to report previous HIV
      testing. Also, those who had attended an HIV/AIDS education workshop or
      discussion and those who reported knowing persons living with HIV/AIDS were more
      likely to report previous testing. However, HIV testing was not associated with
      condom use or with the number of sexual partners. CONCLUSIONS: The lack of
      significant findings establishing a relationship between testing and risky sexual
      behaviours should not negate the importance of HIV testing. Being informed
      regarding personal HIV serostatus is one of the first steps in self-protection.
      Effective messages and programmes promoting HIV testing need to be developed and
      implemented in Jamaica, in order to educate people about how to assess their
      level of risk with respect to contracting HIV infection.

PMID- 16630036
TI  - Changes in sleep quality and brain wave patterns following initiation of an
      efavirenz-containing triple antiretroviral regimen.
AB  - BACKGROUND: Initiation of efavirenz is commonly associated with sleep
      disturbances. Assessment of sleep using the electroencephalogram and
      electromyogram enables sleep staging to be performed and changes following the
      introduction of therapy to be evaluated. METHODOLOGY: Using standardized sleep
      staging methodology, we investigated sleep staging and sleep quality by patient
      self-report in an open-label cohort pilot study. Assessments were performed prior
      to the initiation of efavirenz, 2 weeks after the initiation of efavirenz and 3
      months after the initiation of efavirenz. The study included HIV-positive
      individuals without central neurological disease who were naive to antiretroviral
      treatment. All patients initiated treatment with two nucleoside reverse
      transcriptase inhibitors in combination with efavirenz. RESULTS: Ten patients
      completed all three study visits. Patients reported an increase in recollection
      of dreams and morning sluggishness after the initiation of efavirenz which
      persisted for 3 months. Sleep-staging data indicated a modest reduction in stage
      2 sleep with a corresponding increase in deep sleep stage 4 and a modest increase
      in rapid eye movement (REM) sleep. Overall sleep maintenance efficiency did not
      significantly change from baseline. Changes in sleep staging were most marked 2
      weeks after the initiation of efavirenz but remained different from baseline
      patterns at 3 months. CONCLUSION: The data indicate that efavirenz has a modest
      but persistent impact on the time spent in several key sleep stages. Patients
      reported persistence of dream recollection but remained satisfied with sleep
      quality and overall quality of life.

PMID- 16630037
TI  - Role of individualization of hepatitis C virus (HCV) therapy duration in HIV/HCV
      coinfected individuals.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy, safety and
      tolerability of pegylated interferon and ribavirin in HIV/hepatitis C virus (HCV)
      coinfected patients, prescribed for the same duration and at the same dosage as
      that used in HCV monoinfection studies. DESIGN: It was an open-label, single
      centre, prospective study. METHODS: Forty-five patients coinfected with HIV and
      HCV with CD4 counts >200 cells/microL were treated with pegylated interferon
      alpha2b 1.5 microg/kg/week and ribavirin 1000-1200 mg/day for 24-48 weeks
      depending on HCV genotype. Safety and tolerability were assessed weekly for the
      first month and monthly thereafter. Virological response was assessed at weeks 4,
      12 and 24 and at the end of treatment and 12 and 24 weeks post completion of
      treatment. The primary endpoint was defined as undetectable HCV RNA at 24 weeks
      post completion of treatment [sustained virological response (SVR)]. RESULTS: The
      majority of patients were male and had been injecting drug users. Sixty per cent
      were on antiretroviral therapy. In an intention-to-treat analysis, 53% had an SVR
      (genotype 1, 19% and genotype 2/3, 75%). All patients who had undetectable HCV
      RNA at week 4 of HCV treatment [very early virological response (VEVR)] had a
      SVR. On multivariate analysis only HCV genotype predicted SVR. Adverse events
      occurred frequently. CONCLUSIONS: These results indicate that 24 weeks of HCV
      treatment may be adequate for HIV-infected individuals coinfected with HCV
      genotype 2 or 3. VEVR can predict SVR in this group and may be used to guide the
      subgroup of genotype 2/3 individuals who will respond to 24 weeks of treatment.

PMID- 16630038
TI  - Maternal hepatotoxicity with nevirapine as part of combination antiretroviral
      therapy in pregnancy.
AB  - OBJECTIVES: To describe the maternal tolerability of nevirapine as part of
      combination antiretroviral therapy in pregnancy at three HIV centres in Dublin,
      Ireland and to determine risk factors for development of significant
      hepatotoxicity. METHODS: A retrospective study was carried out of all women
      prescribed nevirapine as part of combination antiretroviral therapy in pregnancy
      at three HIV centres in Dublin, Ireland (October 2000 to February 2003).
      Toxicities experienced were graded according to the Division of AIDS toxicity
      guidelines for adults. Statistical analysis was performed to determine whether
      there were differences between those that did and those that did not experience
      significant hepatotoxicity. RESULTS: A total of 123 women initiated nevirapine as
      part of combination antiretroviral therapy in the study period. Eight women
      developed significant hepatotoxicity, including two women who died from fulminant
      hepatitis. Women who experienced more severe hepatotoxicity had higher
      pretreatment CD4 counts (P=0.01). CONCLUSIONS: In this cohort, women who
      experienced more severe hepatotoxicity had higher pretreatment CD4 counts,
      lending additional weight to the need for caution in using nevirapine as part of
      combination antiretroviral therapy in women not requiring antiretroviral therapy
      for their own health.

PMID- 16630039
TI  - Incidence and risk factors of bacterial pneumonia requiring hospitalization in
      HIV-infected patients started on a protease inhibitor-containing regimen.
AB  - OBJECTIVE: To describe the incidence and risk factors of bacterial pneumonia
      occurring in patients treated with antiretrovirals. METHODS: In the ongoing
      APROCO (Anti-proteases) cohort, 1281 patients at the initiation of a protease
      inhibitor (PI)-containing antiretroviral regimen were enrolled from 1997-1999.
      All events requiring hospitalization during follow up are recorded. Of these,
      bacterial pneumonia was defined as the occurrence of a new pulmonary infiltrate
      with fever and either evidence of a bacteriological cause (definite cases) or
      favourable outcome with antimicrobial therapy (presumptive cases). Risk factors
      of bacterial pneumonia were studied using survival analyses. RESULTS: During a
      median follow up of 43 months, 29 patients had at least one episode of bacterial
      pneumonia, giving an incidence of 0.8/100 patient years. The 11 definite cases
      were attributable to Streptococcus pneumoniae (n=9), Legionella pneumophila (n=1)
      and Haemophilus influenzae (n=1). In multivariate analysis, bacterial pneumonia
      was significantly more frequent in older patients, injecting drug users, patients
      having a CD4 cell count>500 cells/microL at baseline and patients who initiated
      PI therapy with nonboosted saquinavir. It was significantly less frequent in
      nonsmokers. The occurrence of bacterial pneumonia was also associated with lower
      self-reported adherence to antiretroviral therapy and to higher plasma HIV-1 RNA
      levels during follow-up. CONCLUSIONS: Bacterial pneumonia occurs rarely in
      patients treated with a PI-containing regimen and may be associated with
      virological failure.

PMID- 16630040
TI  - Regulation of adiponectin in adipocytes upon exposure to HIV-1.
AB  - OBJECTIVES: Adipose dysregulation, dyslipidemia, and insulin resistance are
      hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these
      disturbances are unknown. In HIV-infected patients, we previously demonstrated a
      strong relationship between lipodystrophy and levels of adiponectin, an adipose
      peptide implicated in regulation of glucose and lipid metabolisms. In this study
      we investigated the effect of HIV on adipocytes, to determine whether HIV can
      directly infect adipocytes and/or alter the regulation and secretion of the
      adipocyte-derived hormone adiponectin. METHODS: Human subcutaneous preadipocytes
      and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was
      measured in supernatants and cell lysates. RESULTS: Although adipocytes expressed
      CD4, the major HIV receptor, they could not be infected in vitro. However,
      exposure to HIV dramatically increased the secretion of adiponectin from human
      adipocytes, in the absence of infection. This was exacerbated with sustained
      exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells
      also produced adiponectin, but this was largely dependent upon T-cell activation.
      CONCLUSIONS: We propose that the stimulation of adiponectin production by HIV can
      perturb adiponectin regulation, leading to substantially decreased levels upon
      viral suppression by antiretroviral therapy. These data suggest a potential
      molecular mechanism of adiponectin regulation in HIV-infected patients.

PMID- 16630041
TI  - Assessing evidence from clinical trials in chronic hepatitis C.
AB  - Hepatitis C is a global problem with significantly associated morbidity and
      mortality. Although some recent therapeutic advances have shown rates of
      sustained virologic remission of 50% or higher, combination therapy with
      interferon and ribavirin is often not well tolerated and is giving rise to a
      growing number of nonresponders. As a result, a large number of experimental
      drugs for the treatment of chronic hepatitis C are in development. As the
      clinical trial reports are made available, physicians need to become familiar
      with issues related to the design of these studies and to develop strategies to
      interpret the evidence they yield. The articles in this supplement describe the
      issues in clinical trial design and the evaluation of evidence from clinical
      trials in patients with chronic hepatitis C.

PMID- 16630042
TI  - Issues in designing and interpreting clinical trials of treatments for chronic
      hepatitis C.
AB  - Many of the major advances in treating patients for chronic hepatitis C have been
      made based on the results of randomized, double-blind, controlled clinical
      trials. However, given the large number of hepatitis C medications in
      development, physicians need to understand the unique elements and types of
      clinical trials in order to make accurate comparisons of differing drug efficacy
      claims. Clinicians also need to be aware of the various factors that can
      influence the outcomes and interpretations of these trials, irrespective of the
      intervention under study. For example, similar trials conducted in the United
      States and Europe may have different outcomes simply because the study
      populations differ. Thus, both trial design and patient population are important
      considerations in the design and analysis of clinical trials for patients with
      chronic hepatitis C.

PMID- 16630043
TI  - Evaluating the evidence from clinical trials in chronic hepatitis C.
AB  - A number of studies are being published on investigational agents for the
      treatment of patients with chronic hepatitis C. Before incorporating new
      medications into therapy or electing to postpone therapy until an investigational
      agent receives regulatory approval, it is important to evaluate the following
      specific features of the published evidence: quality of the evidence, precision
      of the treatment effect, magnitude of the treatment effect, magnitude of the
      hazards, and other factors such as risk-benefit analysis and cost, including cost
      effectiveness. Previous studies of treatment of patients with the disease allow
      us to establish some benchmarks and provide structure to evaluate the evidence of
      the efficacy and safety of these newer drugs.

PMID- 16630044
TI  - Evaluation of epitope tags for protein detection after in vivo CNS gene transfer.
AB  - Functional characterization of disease-related proteins, their splice variants
      and dominant negative mutants in the context of complex CNS tissues such as brain
      and retina is frequently assessed by in vivo gene transfer. For correct
      interpretation of results it is imperative that the protein under investigation
      is unambiguously detected in the transduced cell types and can be distinguished
      from any endogenously expressed physiological variants. Therefore the first
      systematic evaluation of epitope tags used to trace ectopically expressed
      proteins in the central nervous system is presented here. Substantial differences
      in the performances of various epitope tag-antibody combinations with respect to
      sensitivity, specificity and influence of the epitope tag on the fusion protein
      are elucidated. Epitope tags already established for protein detection in vitro
      and to some extent in vivo (c-Myc, HA and FLAG tags) were immunohistochemically
      detected with high sensitivity. However, detection of these tags revealed
      problems with background staining and we also document structural and functional
      influence of the tags on the fusion protein. In order to prevent such unwanted
      side-effects, epitope tags which have not yet been used for in vivo applications
      (IRS, EE and AU1 tags) were characterized in brain, retina and cultured neurons.
      While use of the IRS and EE tags was hindered by low sensitivity or specificity,
      optimal results were obtained with the AU1 epitope, which may develop into a
      standard tool for detection of ectopic protein expression in the central nervous
      system.

PMID- 16630045
TI  - Endogenous factors derived from embryonic cortex regulate proliferation and
      neuronal differentiation of postnatal subventricular zone cell cultures.
AB  - In rodents, the subventricular zone (SVZ) harbours neural stem cells that
      proliferate and produce neurons throughout life. Previous studies showed that
      factors released by the developing cortex promote neurogenesis in the embryonic
      ventricular zone. In the present report, we studied in the rat the possible
      involvement of endogenous factors derived from the embryonic cortex in the
      regulation of the development of postnatal SVZ cells. To this end, SVZ
      neurospheres were maintained with explants or conditioned media (CM) prepared
      from embryonic day (E) 13, E16 or early postnatal cortex. We demonstrate that
      early postnatal cortex-derived factors have no significant effect on SVZ cell
      proliferation or differentiation. In contrast, E13 and E16 cortex release
      diffusible, heat-labile factors that promote SVZ cell expansion through increased
      proliferation and reduced cell death. In addition, E16 cortex-derived factors
      stimulate neuronal differentiation in both early postnatal and adult SVZ
      cultures. Fibroblast growth factor (FGF)-2- but not epidermal growth factor (EGF)
      immunodepletion drastically reduces the mitogenic effect of E16 cortex CM, hence
      suggesting a major role of endogenous FGF-2 released by E16 cortex in the
      stimulation of SVZ cell proliferation. The evidence we provide here for the
      regulation of SVZ cell proliferation and neuronal differentiation by endogenous
      factors released from embryonic cortex may be of major importance for brain
      repair research.

PMID- 16630046
TI  - L-glutamate activates RhoA GTPase leading to suppression of astrocyte stellation.
AB  - The actin cytoskeleton is known to support cellular morphological changes. Rho
      family small GTPases function as switching molecules to promote the convergence
      of both extracellular and intracellular signals in regulating cytoskeletal
      organization. Evidence indicates that L-glutamate suppresses morphological
      changes of astrocytes over a broad spectrum. To test the possibility that L
      glutamate affects cytoskeletal reorganization, we investigated its effect on
      morphological changes induced by manganese exposure. L-glutamate concentration
      dependently prevented and reversed manganese-induced astrocyte stellation and
      cytoskeletal disruption. The suppressive effect of L-glutamate on manganese
      induced stellation was mediated by the activation of the glutamate transporter
      rather than ionotropic or metabotropic glutamate receptors. Pharmacological and
      biochemical approaches revealed the involvement of Ras homolog gene family,
      member A (RhoA) activation in L-glutamate-mediated suppression of manganese
      induced stellation. The activation of RhoA by L-glutamate was partly through the
      up-regulation of guanine nucleotide exchange factor phosphorylation and was
      abrogated by competitive nonsubstrate inhibitors. Furthermore, the
      hyperphosphorylation of myosin light chain and cofilin through the activation of
      RhoA following L-glutamate treatment synergistically stabilized actin stress
      fibres. These results suggest that manganese-induced stellation is suppressed by
      a mechanism involving glutamate transporters. Our in vitro findings also strongly
      indicate that astrocyte morphological plasticity is under the control of RhoA and
      that manganese and L-glutamate regulate astrocyte morphology by modulating this
      switching molecule under culture conditions.

PMID- 16630047
TI  - Spontaneous locomotor recovery in spinal cord injured rats is accompanied by
      anatomical plasticity of reticulospinal fibers.
AB  - Although injured axons in mammalian spinal cords do not regenerate, some recovery
      of locomotor function following incomplete injury can be observed in patients and
      animal models. Following a lateral hemisection injury of the thoracic spinal
      cord, rats spontaneously recover weight-bearing stepping in the hind limb
      ipsilateral to the injury. The mechanisms behind this recovery are not completely
      understood. Plasticity in the reticulospinal tract (RtST), the tract responsible
      for the initiation of walking, has not been studied. In this study, rats received
      lateral thoracic hemisection of the spinal cord, and RtST projections were
      compared in two groups of rats, one early in recovery (7 days) and the other at a
      time point when weight-bearing stepping was fully regained (42 days). We found
      that this recovery occurs in parallel with increased numbers of collaterals of
      spared RtST fibers entering the intermediate lamina below the injury at L2.
      Sprouting of injured RtST fibers above the lesion was not found. In conclusion,
      our study suggests that sprouting of spared RtST fibers might be involved in the
      recovery of locomotion following incomplete spinal cord injury.

PMID- 16630048
TI  - Mice lacking L1 cell adhesion molecule have deficits in locomotion and exhibit
      enhanced corticospinal tract sprouting following mild contusion injury to the
      spinal cord.
AB  - L1 is a member of the immunoglobulin superfamily of cell adhesion molecules that
      is associated with axonal growth, including formation of the corticospinal tract
      (CST). The present study describes the effects of L1 deletion on hindlimb
      function in locomotion, and examines the role of L1 in recovery and remodeling
      after contusive spinal cord injury (SCI) in mice. Uninjured adult L1 knockout (Y/
      ) mice had impaired performance on locomotor tests compared with their wild-type
      littermates (Y/+). Anterograde tracing demonstrated that CST axons project to
      thoracic, but not lumbar, levels of the spinal cord of Y/- mice, and revealed a
      diversion of these fibers from their position in the base of the dorsal columns.
      Retrograde tracing also revealed reduced numbers of descending projections from
      paraventricular hypothalamus and red nuclei to the lumbar spinal cord in Y/-
      mice. SCI at the mid-thoracic level produced a lesion encompassing the center of
      the spinal cord, including the site of the dorsal CST and surrounding gray matter
      (GM). The injury caused lasting deficits in fine aspects of locomotion. There was
      no effect of genotype on final lesion size or the growth of axons into the lesion
      area. However, injured Y/- mice demonstrated a robust expansion of CST
      projections throughout the GM of the cervical and thoracic spinal cord rostral to
      the lesion compared with Y/+ littermates. Thus, L1 is important for the
      development of multiple spinal projections and also contributes to the
      restriction of CST sprouting rostral to the site of a SCI in adults.

PMID- 16630049
TI  - Activity of fin muscles and fin motoneurons during swimming motor pattern in the
      lamprey.
AB  - Coordination of motoneuron activity is a fundamental prerequisite for the
      generation of functional locomotor patterns. We investigate the neural mechanisms
      that coordinate activity of motoneuron pools in the vertebrate spinal cord with
      differing phases of activity in the locomotor cycle in a simple motor system, the
      lamprey swimming network. In the region of dorsal fins the lamprey spinal cord
      contains two groups of motoneurons: the myotomal motoneurons that innervate the
      trunk muscles; and the fin motoneurons controlling muscle fibres of the dorsal
      fins. We investigated the activity of fin muscles during swimming in vivo and
      that of fin motoneurons during fictive swimming in vitro. During swimming in vivo
      with cycle periods of 4-8 Hz, fin muscle activity covered a broad portion of the
      cycle, with the peak of activity out-of-phase to the ipsilateral myotomal
      muscles. During fictive swimming evoked by N-methyl-d-aspartate in the isolated
      spinal cord, fin motoneurons expressed similar out-of-phase activity. The phase
      relationship of the synaptic drive to fin motoneurons was examined by recording
      their activity intracellular during fictive swimming. Three different forms of
      membrane potential oscillation with different time courses in the locomotor cycle
      could be distinguished. Sagittal lesions of the spinal cord in the segment where
      fin motoneurons are recorded and up to one segment rostral and caudal from it did
      not influence the out-of-phase activity pattern of the motoneurons. Our results
      indicate that coordination of fin motoneuron activity with the locomotor activity
      of myotomal motoneurons does not depend on intrasegmental contralateral premotor
      elements.

PMID- 16630050
TI  - Expression of microsomal epoxide hydrolase is elevated in Alzheimer's hippocampus
      and induced by exogenous beta-amyloid and trimethyl-tin.
AB  - The brain is a potential target for drugs and environmental toxins. Microsomal
      epoxide hydrolase (mEH) is one of several critical biotransformation enzymes in
      xenobiotic metabolism and detoxification. In the present study, we report that
      the expression of mEH is significantly elevated in the hippocampus and associated
      cortex, but not in the cerebellum, in Alzheimer's disease (AD) patients. A large
      proportion of the mEH-positive cells are located around beta-amyloid plaques. The
      mEH-positive-staining cells are astrocytes and pyramidal neurons. Western
      blotting analysis confirmed increased expression of mEH in AD hippocampal
      tissues. In primary hippocampal glial culture, beta-amyloid aggregation
      stimulated mEH expression in the astrocytes, which displayed a patchy
      distribution. An environmental neurotoxic agent, trimethyl-tin, also activated
      mEH expression in rat hippocampus and entorhinal cortex. The present study
      demonstrates a significant increase in mEH expression in the AD hippocampus, a
      region showing abundant neuropathology in AD. The expression of mEH could also be
      elevated by exposure to exogenous beta-amyloid in vitro and environmental toxins
      in vivo. Our studies suggest that mEH may play a role in pathogenesis of
      neurodegeneration in response to environmental stress.

PMID- 16630051
TI  - Non-fibrillar beta-amyloid abates spike-timing-dependent synaptic potentiation at
      excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA
      receptors.
AB  - Cognitive decline in Alzheimer's disease (AD) stems from the progressive
      dysfunction of synaptic connections within cortical neuronal microcircuits.
      Recently, soluble amyloid beta protein oligomers (Abeta(ol)s) have been
      identified as critical triggers for early synaptic disorganization. However, it
      remains unknown whether a deficit of Hebbian-related synaptic plasticity occurs
      during the early phase of AD. Therefore, we studied whether age-dependent Abeta
      accumulation affects the induction of spike-timing-dependent synaptic
      potentiation at excitatory synapses on neocortical layer 2/3 (L2/3) pyramidal
      cells in the APPswe/PS1dE9 transgenic mouse model of AD. Synaptic potentiation at
      excitatory synapses onto L2/3 pyramidal cells was significantly reduced at the
      onset of Abeta pathology and was virtually absent in mice with advanced Abeta
      burden. A decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA)/N-methyl-D-aspartate (NMDA) receptor-mediated current ratio implicated
      postsynaptic mechanisms underlying Abeta synaptotoxicity. The integral role of
      Abeta(ol)s in these processes was verified by showing that pretreatment of
      cortical slices with Abeta((25-35)ol)s disrupted spike-timing-dependent synaptic
      potentiation at unitary connections between L2/3 pyramidal cells, and reduced the
      amplitude of miniature excitatory postsynaptic currents therein. A robust
      decrement of AMPA, but not NMDA, receptor-mediated currents in nucleated patches
      from L2/3 pyramidal cells confirmed that Abeta(ol)s perturb basal glutamatergic
      synaptic transmission by affecting postsynaptic AMPA receptors. Inhibition of
      AMPA receptor desensitization by cyclothiazide significantly increased the
      amplitude of excitatory postsynaptic potentials evoked by afferent stimulation,
      and rescued synaptic plasticity even in mice with pronounced Abeta pathology. We
      propose that soluble Abeta(ol)s trigger the diminution of synaptic plasticity in
      neocortical pyramidal cell networks during early stages of AD pathogenesis by
      preferentially targeting postsynaptic AMPA receptors.

PMID- 16630052
TI  - Muscarinic autoreceptors modulate transmitter release through protein kinase C
      and protein kinase A in the rat motor nerve terminal.
AB  - We have used intracellular recording to investigate the existence of a functional
      link between muscarinic presynaptic acetylcholine (ACh) autoreceptors, the
      intracellular serine-threonine kinases-mediated transduction pathways and
      transmitter release in the motor nerve terminals of adult rats. We found the
      following. (1) Transmitter release was reduced by the M1 muscarinic acetylcholine
      receptor (mAChR) blocker pirenzepine and enhanced by the M2 blocker
      methoctramine. The unselective mAChR blocker atropine increased ACh release,
      which suggests the unmasking of another parallel release-potentiating mechanism.
      There are therefore two opposite, though finely balanced, M1-M2 mAChR-operated
      mechanisms that tonically modulate transmitter release. (2) Both M1 and M2
      mechanisms were altered when protein kinase C (PKC), protein kinase A (PKA) or
      the P/Q-type calcium channel were blocked. (3) Both PKC and PKA potentiated
      release when they were specifically stimulated [with phorbol 12-myristate 13
      acetate (PMA) and Sp-8-Br cAMPs, respectively], and both needed the P/Q channel.
      (4) In normal conditions PKC seemed not to be directly involved in transmitter
      release (the PKC blocker calphostin C did not reduce release), whereas PKA was
      coupled to potentiate release (the PKA blocker H-89 reduced release). However,
      when an imbalance of the M1-M2 mAChRs function was experimentally produced with
      selective blockers, an inversion of the kinase function occurred and PKC could
      then stimulate transmitter release, whereas PKA was uncoupled. (5) The muscarinic
      function may be explained by the existence of an M1-mediated increased PKC
      activity-dependent potentiation of release and an M2-mediated PKA decreased
      activity-dependent release reduction. These findings show that there is a precise
      interrelation pattern of the mAChRs, PKC and PKA in the control of the
      neurotransmitter release.

PMID- 16630054
TI  - Pro-opiomelanocortin colocalizes with corticotropin- releasing factor in axon
      terminals of the noradrenergic nucleus locus coeruleus.
AB  - We previously demonstrated that the opioid peptide enkephalin and corticotropin
      releasing factor (CRF) are occasionally colocalized in individual axon terminals
      but more frequently converge on common dendrites in the locus coeruleus (LC). To
      further examine potential opioid cotransmitters in CRF afferents we investigated
      the distribution of pro-opiomelanocortin (POMC), the precursor that yields the
      potent bioactive peptide beta-endorphin, with respect to CRF immunoreactivity
      using immunofluorescence and immunoelectron microscopic analyses of the LC.
      Coronal sections were collected through the dorsal pontine tegmentum of rat brain
      and processed for immunocytochemical detection of POMC and CRF or tyrosine
      hydroxylase (TH). POMC-immunoreactive processes exhibited a distinct distribution
      within the LC as compared to the enkephalin family of opioid peptides.
      Specifically, POMC fibers were enriched in the ventromedial aspect of the LC with
      fewer fibers present dorsolaterally. Immunofluorescence microscopy showed
      frequent coexistence of POMC and CRF in varicose processes that overlapped TH
      containing somatodendritic processes in the LC. Ultrastructural analysis showed
      POMC immunoreactivity in unmyelinated axons and axon terminals. Axon terminals
      containing POMC were filled with numerous large dense-core vesicles. In sections
      processed for POMC and TH, approximately 29% of POMC-containing axon terminals (n
      = 405) targeted dendrites that exhibited immunogold-silver labeling for TH. In
      contrast, sections processed for POMC and CRF showed that 27% of POMC-labeled
      axon terminals (n = 657) also exhibited CRF immunoreactivity. Taken together,
      these data indicate that a subset of CRF afferents targeting the LC contain POMC
      and may be positioned to dually impact LC activity.

PMID- 16630053
TI  - Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat
      trigeminal ganglia neurons.
AB  - Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the
      underlying pathophysiology of migraine and other diseases involving neurogenic
      inflammation. We have tested the hypothesis that nitric oxide might trigger
      signaling mechanisms within the trigeminal ganglia neurons that would
      coordinately stimulate CGRP synthesis and release. Treatment of primary
      trigeminal ganglia cultures with nitric oxide donors caused a greater than four
      fold increase in CGRP release compared with unstimulated cultures. Similarly,
      CGRP promoter activity was also stimulated by nitric oxide donors and
      overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the
      antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP
      promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric
      oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling
      pathways, but rather, nitric oxide action required extracellular calcium and
      likely involves T-type calcium channels. Furthermore, nitric oxide was shown to
      increase expression of the active forms of the mitogen-activated protein kinases
      Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in
      trigeminal neurons. In summary, our results provide new insight into the cellular
      mechanisms by which nitric oxide induces CGRP synthesis and secretion from
      trigeminal neurons.

PMID- 16630055
TI  - Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse
      brains during fasting.
AB  - Impaired brain glucose uptake/metabolism precedes the symptoms of Alzheimer
      disease (AD) and is likely to play a role in the development of the disease, but
      the mechanism by which it contributes to AD is not understood. Because glucose
      uptake/metabolism regulates protein O-GlcNAcylation, and the latter modulates
      phosphorylation of tau inversely, we investigated, in fasting Kunming mice,
      whether impaired brain glucose uptake/metabolism causes abnormal
      hyperphosphorylation of tau and, consequently, facilitates the neurofibrillary
      degeneration of AD via down-regulation of tau O-GlcNAcylation. We found that
      fasting caused decreased tau O-GlcNAcylation and concurrent hyperphosphorylation
      of tau at most of the phosphorylation sites studied. The hippocampus was found
      more vulnerable to the tau alterations than the cerebral cortex, which is
      consistent with the fact that it is the hippocampus that is first affected in AD.
      Furthermore, hyperphosphorylation of tau induced by fasting was reversible in the
      brain after re-feeding. These findings provide a novel mechanism explaining how
      impaired brain glucose uptake/metabolism contributes to AD and suggest that it
      may be feasible to treat AD by reversing the abnormal hyperphosphorylation of tau
      at early stages of the disease.

PMID- 16630056
TI  - Preservation of functional architecture in visual cortex of cats with
      experimentally induced hydrocephalus.
AB  - We investigated how neural function is preserved or matured in the visual cortex
      of cats, following the induction of hydrocephalus by kaolin injection. In vivo
      optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats
      revealed orientation maps showing the orderly arrangement of preferred
      orientations when stimulated by grating stimuli at a low spatial frequency,
      whereas stimulus-evoked intrinsic signals in response to gratings at a high
      spatial frequency were often too weak to construct orientation maps. Furthermore,
      in two of the three hydrocephalic cats, initially deteriorated orientation maps
      became almost regular maps in the second imaging experiments conducted 8 and 11
      weeks, respectively, after the first imaging. This indicates that, despite large
      structural deformation of the hydrocephalic brain, orientation maps are
      elaborated sufficiently after the age of 5-6 months, by which time the
      orientation map formation is usually completed in normal cats. Single unit
      recording from the decompressed visual cortex revealed that many neurons showed
      normal orientation selectivity, whereas the binocularity of these neurons was
      found to be reduced. These results suggested that the deformed visual cortex of
      hydrocephalic cats exhibits a high plasticity, retaining its functional
      organization.

PMID- 16630057
TI  - Consequences of unilateral nigrostriatal denervation on the thalamostriatal
      pathway in rats.
AB  - The position of the caudal intralaminar nuclei within basal ganglia circuitry has
      largely been neglected in most studies dealing with basal ganglia function.
      During the past few years, there has been a growing body of evidence suggesting
      that the thalamic parafascicular nucleus in rodents (PF) exerts a multifaceted
      modulation of basal ganglia nuclei, at different levels. Our aim was to study the
      activity of the thalamostriatal pathway in rats with unilateral dopaminergic
      depletion. The experimental approach comprised first unilateral delivery of 6
      OHDA in the medial forebrain bundle. Thirty days post-lesioning, animals showing
      a clear asymmetry were then subjected to bilateral injection of Fluoro-Gold (FG)
      within the striatum. Subsequently, expression of the mRNA encoding the vesicular
      glutamate transporter 2 (vGLUT2) was detected within thalamostriatal-projecting
      neurons (FG-labeled) by in situ hybridization and the results were confirmed by
      laser-guided capture microdissection microscopy followed by real-time PCR. The
      data showed that there was a marked neuronal loss restricted to PF neurons
      projecting to the dopamine-depleted striatum. Moreover, PF neurons innervating
      the dopamine-depleted striatum were intensely hyperactive. These neurons showed a
      marked increase on the expression of vGLUT2 mRNA as well as for the mRNA encoding
      the subunit I of cytochrome oxidase as compared with those neurons projecting to
      the striatum with normal dopamine content. Thus, the selective neurodegeneration
      of PF neurons innervating the striatum together with the increased activity of
      the thalamostriatal pathway coexist after nigrostriatal denervation.

PMID- 16630058
TI  - Multiple isoforms of the tumor protein p73 are expressed in the adult human
      telencephalon and choroid plexus and present in the cerebrospinal fluid.
AB  - p73, a homolog of the p53 tumor suppressor, codes for full-length transactivating
      (TA) and N-terminally truncated (DeltaN) isoforms, with pro- and anti-apoptotic
      activities, respectively. We examined the expression of the main p73 isoforms in
      adult human and mouse telencephalon and choroid plexus by immunohistochemistry on
      paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal
      fluid (CSF), using antibodies against different protein domains. Cortical neurons
      expressed TAp73 predominantly in the cytoplasm and DeltaNp73 mainly in the
      nucleus, with partial overlap in the cytoplasm. Highest expression was found in
      the hippocampus. IB showed an array of TAp73 variants in adult human cortex and
      hippocampus. IB of human choroid plexus and CSF using TAp73-specific antibodies
      revealed the presence of a approximately 90-kDa protein whose molecular weight
      was reduced after N-deglycosylation, suggesting that glycosylated TAp73 is
      exported into the CSF. In the mouse, high expression of TAp73 was also detected
      in the subcommissural organ (SCO), an ependymal gland absent in adult humans.
      TAp73 colocalized with anti-fibra-Reissner-antibody (AFRU), which is a marker of
      Reissner's fiber, the secreted SCO product. p73-deficient mice had generalized
      cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size
      reduction of the choroid plexus. However, the SCOs were apparently unaltered and
      continued to secrete Reissner's fiber. Our findings point to complex and
      widespread p73 activities in the maintenance of adult cortical neurons and in
      brain homeostasis. TAp73 in the CSF may play important roles in the maintenance
      of the adult ventricular wall as well as in the development of the proliferating
      neuroepithelium.

PMID- 16630059
TI  - Neural progenitor cells engineered to secrete GDNF show enhanced survival,
      neuronal differentiation and improve cognitive function following traumatic brain
      injury.
AB  - We sought to evaluate the potential of C17.2 neural progenitor cells (NPCs)
      engineered to secrete glial cell line-derived neurotrophic factor (GDNF) to
      survive, differentiate and promote functional recovery following engraftment into
      the brains of adult male Sprague-Dawley rats subjected to lateral fluid
      percussion brain injury. First, we demonstrated continued cortical expression of
      GDNF receptor components (GFRalpha-1, c-Ret), suggesting that GDNF could have a
      physiological effect in the immediate post-traumatic period. Second, we
      demonstrated that GDNF over-expression reduced apoptotic NPC death in vitro.
      Finally, we demonstrated that GDNF over-expression improved survival, promoted
      neuronal differentiation of GDNF-NPCs at 6 weeks, as compared with untransduced
      (MT) C17.2 cells, following transplantation into the perilesional cortex of rats
      at 24 h post-injury, and that brain-injured animals receiving GDNF-C17.2
      transplants showed improved learning compared with those receiving vehicle or MT
      C17.2 cells. Our results suggest that transplantation of GDNF-expressing NPCs in
      the acute post-traumatic period promotes graft survival, migration, neuronal
      differentiation and improves cognitive outcome following traumatic brain injury.

PMID- 16630060
TI  - Delayed ischemic electrocortical suppression during rapid repeated cerebral
      ischemia and kainate-induced seizures in rat.
AB  - Global cerebral ischemia induces, within seconds, suppression of spontaneous
      electrocortical activity, partly due to alterations in synaptic transmission. In
      vitro studies have found that repeated brief hypoxic episodes prolong the
      persistence of synaptic transmission due to weakened adenosine release. The aim
      of this study was to investigate in vivo whether the time to ischemic
      electrocortical suppression (T(ES)) could be altered during energy stress
      conditions such as rapid repeated global cerebral ischemia and kainate-induced
      seizures. Experiments were carried out in adult rats under chloral hydrate
      anaesthesia. Repeated episodes of 1 min of ischemia were induced by transiently
      clamping the carotid arteries in a 'four-vessel occlusion' model. We devised an
      automatic method of T(ES) estimation based on the decay of the root mean square
      of two-channel electrocorticographic recordings. To distinguish the alterations
      in spontaneous electrocortical activity we compared T(ES) with the ischemic
      suppression of visual evoked potentials (VEP). During the first ischemic episode,
      T(ES) was approximately 15 s and remained unchanged when five ischemic episodes
      were separated by 10-min reperfusion intervals. When ischemia was repeated after
      2 min of reperfusion T(ES) progressively increased, reaching a plateau value of
      approximately 24 s. A similar plateau was reached during kainate-induced
      seizures. The T(ES) plateau occurred prior to ischemic suppression of VEP. Our
      data suggest that, under conditions of acute metabolic stress in vivo, the
      ischemic suppression of spontaneous electrocortical activity may be delayed up to
      a plateau value. These findings are consistent with the hypothesis of a
      depletable adenosine pool; however, the restoration of synaptic transmission may
      be faster in vivo than in vitro.

PMID- 16630061
TI  - Periparabigeminal and adjoining mesencephalic tegmental field projections to the
      dorsolateral periaqueductal grey in cat - a possible role for oculomotor input in
      the defensive system.
AB  - The dorsolateral column of the mesencephalic periaqueductal grey (PAGdl) differs
      from its adjacent columns in terms of afferent and efferent connections and the
      distribution pattern of different histochemical substances. Functionally, PAGdl
      is associated with aversive and defensive behaviours, but in an earlier study of
      this laboratory [E.M. Klop et al. (2005) J. Comp. Neurol., 492, 303-322], it was
      found that PAGdl specifically receives input from the nucleus prepositus
      hypoglossi, which plays a role in oculomotor control. In search for other
      oculomotor-related brainstem structures projecting to PAGdl we studied the
      projections from the parabigeminal nucleus (PBGN) and its medially adjoining
      periparabigeminal area (PPBGA). In three cats, injections of wheatgerm agglutinin
      horseradish peroxidase involving PAGdl did not, or to only a very limited extent,
      result in retrogradely labelled neurons in PBGN. When the peripheral parts of
      PAGdl were involved in the injection site, labelled neurons were located in
      PPBGA, while after an injection involving only the more central parts of PAGdl
      they were located in the tegmentum medial to the PPBGA. An anterograde tracing
      study using [3H]-leucine and biotinylated dextran amine affirmed that neurons in
      PPBGA project to more peripheral parts of PAGdl, while neurons located in the
      tegmentum medial to PPBGA project mainly to its central parts. These results
      provide further evidence for the existence of two different subdivisions of
      PAGdl. We hypothesize that PAGdl is alerted by sudden changes in the visual
      field, and that the PAGdl defensive system is inhibited when these changes are
      caused by eye movements.

PMID- 16630062
TI  - Evidence for a role of CaMKIV in the development of opioid analgesic tolerance.
AB  - cAMP response-element binding protein (CREB), a transcription factor involved in
      learning, memory and drug addiction, is phosphorylated by calcium-calmodulin
      dependent protein kinase IV (CaMKIV). Here, we show that CaMKIV-knockout (KO)
      mice developed less analgesic tolerance after chronic morphine administration
      with no alteration in physical dependence or acute morphine-induced analgesia.
      The increase in phosphorylated CREB expression observed in wild-type mice after
      chronic morphine was absent in CaMKIV-KO mice, while there was no difference in
      the expression or phosphorylation of the micro-opioid receptor between groups.
      Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the micro
      opioid receptor than did wild-type mice, while uncoupling was similar in control
      wild-type and KO mice. In addition, morphine reduced inhibitory transmission to a
      greater degree in CaMKIV-KO mice than in controls after chronic morphine
      exposure. Our results provide novel evidence for the role of CaMKIV in the
      development of opioid analgesic tolerance but not physical dependence.

PMID- 16630063
TI  - Intravenous self-administration of nicotine is altered by lesions of the
      posterior, but not anterior, pedunculopontine tegmental nucleus.
AB  - The reinforcing properties of nicotine involve actions at nicotinic acetylcholine
      receptors located on dopamine (DA) neurons in the ventral tegmental area (VTA).
      The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of
      these DA neurons, and those of the substantia nigra pars compacta (SNc). The PPTg
      can be subdivided into anterior (aPPTg) and posterior (pPPTg) regions on the
      basis of its innervation of midbrain DA neurons - the pPPTg innervates both VTA
      and SNc while the aPPTg innervates SNc. As the reinforcing actions of nicotine
      depend on its actions in the VTA more than SNc, it was hypothesized that
      excitotoxic lesions of pPPTg would alter nicotine reinforcement, measured by
      intravenous self-administration, while lesions of aPPTg would not. Rats were
      given ibotenate lesions of pPPTg or aPPTg, followed by intravenous
      catheterization. Intravenous self-administration (IVSA) of nicotine (0.03
      mg/kg/inf) was carried out until a stable response baseline was reached. A dose
      response function for nicotine was then established. There was no significant
      effect of aPPTg lesions on nicotine IVSA, while IVSA was significantly elevated
      following pPPTg lesions, compared with both sham lesioned controls and aPPTg
      excitotoxin lesioned rats. This was found across all doses, including saline, of
      the dose-response function. The differential effect of aPPTg lesions and pPPTg
      lesions suggests that disruption of regulatory innervation from pPPTg results in
      altered regulation of VTA DA neurons. The resulting change in nicotine self
      administration behaviour was hypothesized to reflect either a reduction in
      intrinsic nicotine reward value, or enhancement of associative incentive
      salience.

PMID- 16630064
TI  - Rapid-rate transcranial magnetic stimulation of animal auditory cortex impairs
      short-term but not long-term memory formation.
AB  - Bilateral rapid-rate transcranial magnetic stimulation (rTMS) of gerbil auditory
      cortex with a miniature coil device was used to study short-term and long-term
      effects on discrimination learning of frequency-modulated tones. We found
      previously that directional discrimination of frequency modulation (rising vs.
      falling) relies on auditory cortex processing and that formation of its memory
      depends on local protein synthesis. Here we show that, during training over 5
      days, certain rTMS regimes contingent on training had differential effects on the
      time course of learning. When rTMS was applied several times per day, i.e. four
      blocks of 5 min rTMS each followed 5 min later by a 3-min training block and 15
      min intervals between these blocks (experiment A), animals reached a high
      discrimination performance more slowly over 5 days than did controls. When rTMS
      preceded only the first two of four training blocks (experiment B), or when
      prolonged rTMS (20 min) preceded only the first block, or when blocks of
      experiment A had longer intervals (experiments C and D), no significant day-to
      day effects were found. However, in experiment A, and to some extent in
      experiment B, rTMS reduced the within-session discrimination performance.
      Nevertheless the animals learned, as demonstrated by a higher performance the
      next day. Thus, our results indicate that rTMS treatments accumulate over a day
      but not strongly over successive days. We suggest that rTMS of sensory cortex, as
      used in our study, affects short-term memory but not long-term memory formation.

PMID- 16630065
TI  - Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors
      in rats.
AB  - This study investigated the role of the hippocampus in both unconditioned and
      conditioned defensive behaviors by examining the effects of pretraining ibotenic
      acid lesions to the dorsal and ventral hippocampus in male Long-Evans hooded rats
      exposed to three types of threat stimuli: cat-odor, a live cat and footshock.
      Defensive behaviors were assessed during exposure to cat-odor and a live cat, and
      immediately following the presentation of footshock. Conditioned defensive
      behaviors were also assessed in each context 24 h after initial threat exposure.
      During both unconditioned and conditioned trials, dorsal hippocampal lesions
      failed to significantly alter any behavioral measure in each test of defense. In
      contrast, ventral hippocampal lesions significantly reduced unconditioned
      defensive behaviors during exposure to cat-odor without producing any observable
      effects during cat exposure. Furthermore, ventral lesions significantly
      attenuated conditioned defensive behaviors following the administration of
      footshock and during re-exposure to each context. These results suggest a
      specific role for the ventral, not dorsal, hippocampus in modulating anxiety-like
      behaviors in certain animal models of defense.

PMID- 16630066
TI  - Selective representation of task-relevant objects and locations in the monkey
      prefrontal cortex.
AB  - In the monkey prefrontal cortex (PFC), task context exerts a strong influence on
      neural activity. We examined different aspects of task context in a temporal
      search task. On each trial, the monkey (Macaca mulatta) watched a stream of
      pictures presented to left or right of fixation. The task was to hold fixation
      until seeing a particular target, and then to make an immediate saccade to it.
      Sometimes (unilateral task), the attended pictures appeared alone, with a cue at
      trial onset indicating whether they would be presented to left or right.
      Sometimes (bilateral task), the attended picture stream (cued side) was
      accompanied by an irrelevant stream on the opposite side. In two macaques, we
      recorded responses from a total of 161 cells in the lateral PFC. Many cells
      (75/161) showed visual responses. Object-selective responses were strongly shaped
      by task relevance - with stronger responses to targets than to nontargets,
      failure to discriminate one nontarget from another, and filtering out of
      information from an irrelevant stimulus stream. Location selectivity occurred
      rather independently of object selectivity, and independently in visual responses
      and delay periods between one stimulus and the next. On error trials, PFC
      activity followed the correct rules of the task, rather than the incorrect overt
      behaviour. Together, these results suggest a highly programmable system, with
      responses strongly determined by the rules and requirements of the task
      performed.

PMID- 16630067
TI  - No evidence for a substantial involvement of primary motor hand area in
      handedness judgements: a transcranial magnetic stimulation study.
AB  - Twelve right-handed volunteers were asked to judge the laterality of a hand
      stimulus by pressing a button with one of their toes. Judgements were based on
      two-dimensional drawings of the back or palm of a right or left hand at various
      orientations. Suprathreshold single-pulse transcranial magnetic stimulation (TMS)
      was given to the left primary motor hand area (M1-HAND) at 0, 200, 400, 600, 800
      or 1000 ms after stimulus onset to probe the functional involvement of the
      dominant left M1 at various stages of handedness recognition. We found that mean
      reaction times and error rates increased with angle of rotation depending on the
      actual biomechanical constraints of the hand but suprathreshold TMS had no
      influence on task performance regardless of the timing of TMS. However, the
      excitability of the corticomotor output from the left M1-HAND was modulated
      during the reaction. Judging left hand drawings was associated with an
      attenuation of motor-evoked potentials 300-100 ms before the response, whereas
      judging right hand drawings facilitated the motor-evoked potentials only
      immediately before the response. These effects were the same for pictures of
      backs and palms and were independent of the angle of rotation. The failure of TMS
      to affect task performance suggests that there is no time window during which the
      M1-HAND makes a critical contribution to mental rotation of the hand. The
      modulation of motor-evoked potentials according to the laterality of the stimulus
      indicates a secondary effect of the task on corticomotor excitability that is not
      directly related to mental rotation itself.

PMID- 16630068
TI  - ErbB receptor signalling regulates dendrite formation in mouse cerebellar granule
      cells in vivo.
AB  - The formation of morphologically and functionally mature dendrites is a key event
      in neuronal maturation and the establishment of functional neuronal networks, but
      the signals that regulate mammalian dendritic development remain poorly
      understood. Here we show that the erbB receptor signalling pathway, which
      modulates expression of several neurotransmitter receptors, also regulates
      dendritic development of cerebellar granule cells in the intact cerebellum. These
      results suggest that neuregulin-erbB signalling may control a program of
      postsynaptic development, from initiating dendrite morphogenesis to the formation
      and maturation of the postsynaptic apparatus.

PMID- 16630069
TI  - Persistent changes in action potential broadening and the slow
      afterhyperpolarization in rat CA1 pyramidal cells after febrile seizures.
AB  - Febrile (fever-induced) seizures (FS) are the most common form of seizures during
      childhood and have been associated with an increased risk of epilepsy later in
      life. The relationship of FS to subsequent epilepsy is, however, still
      controversial. Insights from animal models do indicate that especially complex FS
      are harmful to the developing brain and contribute to a hyperexcitable state that
      may persist for life. Here, we determined long-lasting changes in neuronal
      excitability of rat hippocampal CA1 pyramidal cells after prolonged (complex) FS
      induced by hyperthermia on postnatal day 10. We show that hyperthermia-induced
      seizures at postnatal day 10 induce a long-lasting increase in the
      hyperpolarization-activated current I(h). Furthermore, we show that a reduction
      in the amount of spike broadening and in the amplitude of the slow
      afterhyperpolarization following FS are also likely to contribute to the
      hyperexcitability of the hippocampus long term.

PMID- 16630070
TI  - Differential effects of alphaCaMKII mutation on hippocampal learning and changes
      in intrinsic neuronal excitability.
AB  - Alpha-calcium/calmodulin-dependent kinase II (alphaCaMKII) is central to synaptic
      plasticity but it remains unclear whether this kinase contributes to neuronal
      excitability changes, which are a cellular correlate of learning. Using knock-in
      mice with a targeted T286A mutation that prevents the autophosphorylation of
      alphaCaMKII (alphaCaMKII(T286A)), we studied the role of alphaCaMKII signaling in
      regulating hippocampal neuronal excitability during hippocampus-dependent spatial
      learning in the Morris water maze. Wild-type control mice showed increased
      excitability of CA1 pyramidal neurons, as assessed by a reduction in the
      postburst afterhyperpolarization (AHP), after spatial training in the water maze.
      Importantly, wild-type mice did not show AHP changes when they were exposed to
      the water maze without the escape platform and swam the same amount of time as
      the trained mice (swim controls), thus manifesting learning-specific increases in
      hippocampal CA1 excitability associated with spatial training. Meanwhile,
      alphaCaMKII(T286A) mice showed impairments in spatial learning but exhibited
      reduced levels of AHP that were similar to wild-type controls after water-maze
      training. Notably, both trained and swim-control groups of alphaCaMKII(T286A)
      mutants showed similar increased excitability, indicating that swimming by itself
      is enough to induce changes in excitability in the absence of normal alphaCaMKII
      function. This result demonstrates dissociation of alphaCaMKII-independent
      changes in intrinsic neuron excitability from learning and synaptic plasticity
      mechanisms, suggesting that increases in excitability per se are not perfectly
      correlated with learning. Our findings suggest that alphaCaMKII signaling may
      function to suppress learning-unrelated changes during training, thereby allowing
      hippocampal CA1 neurons to increase their excitability appropriately for encoding
      spatial memories.

PMID- 16630071
TI  - Divergent thinking training is related to frontal electroencephalogram alpha
      synchronization.
AB  - Cortical activity in the human electroencephalogram alpha band was measured (by
      means of an event-related approach) in a pre- and a post-test (with intermediate
      training) while participants (n = 30) were confronted with divergent thinking
      tasks. Half of the participants received a divergent thinking training (over a
      time period of 2 weeks) which was composed of exercises structurally similar to
      those used in the pre- and post-test. Analyses revealed that the training group
      displayed higher task-related synchronization of frontal alpha activity (i.e.
      increases in alpha power from the pre-stimulus reference to the activation
      interval) than the control group. These findings are in line with the view of
      frontal alpha synchronization as a selective top-down inhibition process that
      prevents internal or top-down information processing being disturbed by incoming
      external input.

PMID- 16630072
TI  - Immune response modifiers--mode of action.
AB  - The innate immune system governs the interconnecting pathways of microbial
      recognition, inflammation, microbial clearance, and cell death. A family of
      evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is
      crucial in early host defense against invading pathogens. Upon TLR stimulation,
      nuclear factor-kappaB activation and the interferon (IFN)-regulatory factor 3
      pathway initiate production of pro-inflammatory cytokines, such as interleukin-1
      and tumor necrosis factor-alpha, and production of type I IFNs (IFN-alpha and IFN
      beta), respectively. The innate immunity thereby offers diverse targets for
      highly selective therapeutics, such as small molecular synthetic compounds that
      modify innate immune responses. The notion that activation of the innate immune
      system is a prerequisite for the induction of acquired immunity raised interest
      in these immune response modifiers as potential therapeutics for viral infections
      and various tumors. A scenario of dermal events following skin cancer treatment
      with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory
      cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii)
      attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from
      the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to
      an increased presentation of tumor antigen in the draining lymph node, and (iv)
      consequently an increased generation of tumor-specific T cells and finally (v) an
      accumulation of tumoricidal effector cells in the treated skin area. The
      induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists
      such as imiquimod might have further benefits by shifting the dominant Th2-type
      response in atopic diseases such as asthma and atopic dermatitis to a more potent
      Th1 response.

PMID- 16630073
TI  - Production and clearance of cyclobutane dipyrimidine dimers in UV-irradiated skin
      pretreated with 1% pimecrolimus or 0.1% triamcinolone acetonide creams in normal
      and atopic patients.
AB  - BACKGROUND: Ultraviolet (UV)-induced pyrimidine dimers are an early step in skin
      carcinogenesis, which is accelerated in the setting of long-term
      immunosuppression with systemic calcineurin inhibitors. It is not known whether
      topical application of calcineurin inhibitors exposes to a similar risk.
      OBJECTIVE: To assess the formation and clearance of UV-induced dipyrimidine
      dimers in human epidermis treated with topical pimecrolimus as compared to
      topical steroid, vehicle and untreated control. METHODS: Pretreated buttock skin
      of 20 human volunteers with (10) or without (10) atopic dermatitis was exposed to
      two minimal erythema doses (MED) of simulated solar radiation. DNA was extracted
      from epidermis 1 and 24 h postirradiation. Pyrimidine dimers were visualized by
      immuno slot blots and quantified by chemoluminescence image analysis. RESULTS:
      One-hour postirradiation, pimecrolimus-treated epidermis contains less DNA damage
      as compared to untreated control, but there were no statistically significant
      differences between pimecrolimus, triamcinolone acetonide and vehicle. Dimer
      levels at 24 h postirradiation showed no significant differences between
      different treatments. CONCLUSION: Treatment with pimecrolimus cream,
      triamcinolone acetonide cream and vehicle is not associated with increased
      epidermal DNA damage at 1 and 24 h post-UV exposure.

PMID- 16630074
TI  - Mechanical stretch induces clustering of beta1-integrins and facilitates
      adhesion.
AB  - Human epithelial cells are permanently stimulated by external mechanical forces.
      The present in vitro study suggests that keratinocytes respond to mechanical
      strain by a coordinated spatial and functional utilization of beta1-integrins and
      the epidermal growth factor receptor (EGFR) with impact to the adhesion
      properties. It was found that a single mechanical stretch applied to HaCaT
      keratinocytes elevates the substrate adhesion, in particular to fibronectin and
      collagen type IV but not to laminin indicating the relevance of beta1-integrins
      in this process. This was confirmed using a functional blocking antibody directed
      against beta1-integrins which reversed the stretch-induced adhesion. Furthermore,
      mechanical stretch gives rise to a rapid redistribution of beta1-integrins in
      clusters on the basal cell membrane, without changing the overall amount of this
      particular integrin subset. Concomitantly, the EGFR co-localizes with beta1
      integrin suggesting a functional cooperation of both membrane proteins in mechano
      signaling. This is corroborated by data showing that stretch-induced activation
      of the EGFR and the downstream element extracellular regulated kinase 1/2
      (ERK1/2) is reversed by preincubation with beta1-integrin antibodies. Vice versa,
      blocking the EGFR using a specific inhibitor abrogates stretch-induced ERK1/2
      activation. In summary, these results show a functional cooperation of beta1
      integrins and EGFR in the adhesion complex supporting the transmission of stretch
      induced signals.

PMID- 16630075
TI  - Activation of Akt by mechanical stretching in human epidermal keratinocytes.
AB  - Mechanical stretching represents an important part of the signaling in skin. We
      have previously demonstrated that mechanical stretching induced proliferative
      phenotypes in human keratinocytes, as shown in increased 5-bromo-2'-deoxyuridine
      (BrdU) incorporation, ERK1/2 activation, and keratin K6 induction. Here we have
      further investigated the antiapoptotic signals in human keratinocytes provoked by
      mechanical stretching in vitro. Keratinocytes were plated on flexible silicone
      supports to transmit mechanical stretching to keratinocytes, involving continuous
      stretching by +20%. Stretching of these cells for 15-30 min caused the
      phosphorylation and activation of Akt. Inhibition of mitogen and extracellular
      signal-regulated kinase (MEK1/2) with U0126 and phosphoinositide 3-OH kinase (PI
      3-K) with Wortmannin attenuated Akt activation. The epidermal growth factor (EGF)
      receptor kinase inhibitor, AG1478, and calcium channel inhibitor, gadolinium
      (Gd3+), also inhibited Akt activation. In summary, our results demonstrate the
      activation of the Akt signaling pathway by mechanical stretching, generating not
      only proliferative but also antiapoptotic signals in human keratinocytes.

PMID- 16630076
TI  - Expression of vanilloid receptor 1 in cultured fibroblast.
AB  - Although the vanilloid receptor 1 (VR1) was originally discovered on primary
      sensory neurons, its broad tissue expression in non-neuronal cells has been
      reported on. Recently, VR1 expression was clearly demonstrated in a variety of
      cutaneous components, such as keratinocytes, glandular epithelium, mast cells and
      sebocytes, except for melanocytes and fibroblasts. However, we demonstrated the
      VR1 expression in the cultured human skin fibroblasts as follows. Previously
      cloned human VR1 primers that corresponded to the expected size of 680 bp by
      reverse transcriptase polymerase chain reaction were identified on the
      fibroblasts, the same as was noted for the positive control, the HaCaT cells. A
      positive immunoreactivity of the VR1 was observed both on fibroblasts and on
      HaCaT cells by Western blotting analysis. Fibroblasts treated with capsaicin, an
      agonist to the VR1, induced significant changes of the membrane current and the
      intracellular calcium level, and these changes were antagonized by capsazepin.
      Capsaicin treatment also showed a positive immunocytochemistry result. Our
      results suggest the existence of VR1 on fibroblasts; this receptor is likely to
      be influenced by ligand-dependent activation.

PMID- 16630077
TI  - Vascular endothelial growth factor gene polymorphisms increase the risk to
      develop psoriasis.
AB  - We investigated the relationship between eight polymorphisms in the gene encoding
      for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C >
      T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type
      psoriasis stratified for age at onset, gender and family history of dermatosis.
      For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy
      subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, 
      1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis
      compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and
      homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped
      together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively].
      Conversely, having the -116AA or +405GG genotype did not significantly increase
      the risk of disease expression compared with other genotypes of the same loci.
      Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA
      homozygous genotypes have a significant two-fold increased risk in developing
      psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19,
      2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as
      compared with controls. On the contrary, we found no phenotype-genotype
      association of the same magnitude among the patients in whom psoriasis developed
      at or before the age of 40 years (early-onset psoriasis) compared with controls.
      Genotype distributions were not significantly different when cases and controls
      were stratified either by gender or family history of psoriasis. Finally, VEGF
      plasma concentration was not significantly different between patients and
      controls and was not correlated with the severity of the disease.

PMID- 16630078
TI  - Association study between catalase gene polymorphisms and the susceptibility to
      vitiligo in Korean population.
AB  - Vitiligo is an acquired pigmentary disorder characterized by well-circumscribed
      depigmented patches. Autoimmune, self-destruction, neural, and genetic theories
      have been proposed for the pathogenesis of vitiligo. Reactive oxygen species play
      an important role in the physiology of cell damage, and catalase is known to
      regulate oxidative stress. Reduced catalase enzyme activity and accumulation of
      excessive hydrogen peroxide were observed in vitiligo. To examine whether
      catalase gene polymorphisms are associated with vitiligo patients in Korean
      population, we investigated two CAT gene polymorphisms including (T/C) BstX I
      (A/T) Hinf I in 118 vitiligo patients and 200 healthy volunteers. The CAT gene
      genotype distribution and allele frequency were not significantly different
      between vitiligo patients and healthy controls. But, the haplotype of two
      polymorphisms was associated with vitiligo. This study suggests possible
      association between the CAT gene and the vitiligo susceptibility.

PMID- 16630079
TI  - Skin immunoglobulin deposition following intravenous immunoglobulin therapy in
      toxic epidermal necrolysis.
AB  - Human intravenous immunoglobulins (IVIg) which contain anti-CD95 antibodies have
      been proposed to treat toxic epidermal necrolysis (TEN). Presently, there is no
      evidence that IVIg reach the keratinocytes in TEN patients. The aim of this study
      was to assess the Ig distribution in the serum, blister fluid and skin of six
      consecutive TEN patients treated with IVIg (1 g/kg/day) for 3 days. They were
      compared with five TEN patients who only received supportive therapy. In all
      patients, IgA, IgM and IgG concentrations were measured in the serum and blister
      fluid using an immuno-nephelometric method. Immunohistochemistry was performed on
      skin biopsies taken from both TEN clinically involved and uninvolved skin to
      search for IgG deposits. On admission, the IgG concentrations were significantly
      higher in both TEN serum and TEN blister fluid compared with their respective IgA
      and IgM contents. The IgG, IgA and IgM concentrations in blister fluid were
      significantly lower than their respective serum concentrations. The serum and
      blister fluid IgG concentrations, but not that of IgA and IgM, were markedly
      increased at the completion of the IVIg treatment. By contrast, they remained
      unchanged in the TEN patients that were untreated with IVIg. In the IVIg-treated
      patients, the IgG intraepidermal deposits raised markedly in both TEN-involved
      and uninvolved skin. This was not the case in patients who did not receive IVIg.
      These results suggest that IVIg perfusions brought a prominent increase in IgG
      concentration in the serum, blister fluid and epidermis of both TEN-involved and
      clinically uninvolved skin. The presence of potentially protective IgG in TEN
      epidermis following IVIg treatment could help limiting the disease progression.

PMID- 16630080
TI  - Atomic force microscopy as an innovative tool for nanoanalysis of native stratum
      corneum.
AB  - This study demonstrates an innovative application of atomic force microscopy
      (AFM). The combination of high-resolution AFM technology and tape stripping is
      presented as a tool for the structure analysis of human stratum corneum (SC) at a
      nanometer scale. Topographic images with a vertical resolution of about 10 nm of
      the SC are presented. Topographical and structural differences between aged and
      young skin can be observed. Aged skin SC is characterized by an increased single
      cell surface area, prominent intercellular gaps and enhanced cell surface
      roughness. The use of AFM in combination with other already established methods,
      e.g. tape stripping in the field of dermatological research will give new
      insights to the structure, function and morphodynamics of SC.

PMID- 16630081
TI  - Pathogenesis and therapy of cutaneous lymphomas--progress or impasse?
AB  - The cutaneous environment hosts a number of hematopoietic neoplasms that are
      dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in
      molecular biology and immunology has provided tools to investigate the
      pathogenesis and the biology of these neoplasms. This review highlights newest
      findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and
      PC T-cell and B-cell lymphomas, speculating how these can be translated into more
      sophisticated, biology-based treatment approaches in the near future.

PMID- 16630082
TI  - Rethinking the exercise electrocardiogram.

PMID- 16630083
TI  - Prediction of left main coronary artery obstruction by 12-lead
      electrocardiography: ST segment deviation in lead V6 greater than or equal to ST
      segment deviation in lead V1.
AB  - BACKGROUND: Acute coronary syndrome (ACS) resulting from culprit lesion in left
      main coronary artery (LMCA) can cause rapid hemodynamic deterioration. It is
      important to identify these patients early to facilitate timely
      revascularization. ST segment elevation in aVR greater than or equal to V(1) (aVR
      V(1)>or= 0) has been suggested as a sensitive predictor of LMCA disease. As a
      result of balanced forces, we hypothesized that ST deviation in V(6) greater than
      or equal to ST deviation in V(1) (V(6)-V(1)>or= 0) might be a good determinant of
      LMCA disease. METHODS: We compared admission 12-lead ECGs of ACS resulting from
      culprit LMCA lesion (n = 75, group I) with ACS resulting from culprit left
      anterior descending lesion (n = 81, group II). Group I was selected over a period
      of 10 years. We compared V(6)-V(1)>or= 0 to aVR-V(1)>or= 0 in both groups. We
      also looked at ratios of ST deviations in V(6),V(1) (V(6)/V(1)>or= 1) and
      aVR,V(1) (aVR/V(1)>or= 1) in patients where ST segment in V(1) was not
      isoelectric (group I = 54 and group II = 55). RESULTS: ST deviation in V(6) was
      significantly greater in group I as compared to group II (P < 0.001). The
      reliabilities of V(6)-V(1)>or= 0, V(6)/V(1)>or= 1, aVR-V(1)>or= 0, and
      aVR/V(1)>or= 1 in predicting LMCA disease were determined. CONCLUSION: This is
      the largest series of ECG analysis on ACS resulting from culprit LMCA lesion.
      V(6)-V(1)>or= 0 and V(6)/V(1)>or= 1 were more sensitive in predicting LMCA as
      culprit vessel in comparison to previously reported greater ST segment elevation
      in aVR than V(1).

PMID- 16630084
TI  - Triggers of sustained monomorphic ventricular tachycardia differ among patients
      with varying etiologies of left ventricular dysfunction.
AB  - BACKGROUND: The mechanisms underlying the initiation of sustained ventricular
      tachycardia (VT) have not been fully elucidated. The extent to which reentry,
      abnormal automaticity, and triggered activity play a role in VT differs depending
      on the etiology of left ventricular dysfunction. By analyzing electrograms from
      implantable cardioverter defibrillator (ICD), we sought to determine whether
      there were differences in VT initiation patterns between patients with ischemic
      and nonischemic cardiomyopathy. METHODS: We analyzed ICD electrograms in patients
      with ejection fractions < 40% who had sustained VT over a 27-month period. The
      trigger for VT onset was classified as a ventricular premature beat (VPB),
      supraventricular tachycardia, or of "sudden onset." The baseline cycle length, VT
      cycle length, coupling interval, and prematurity ratio were recorded for each
      event. The prematurity ratio was calculated as the coupling interval of the VT
      initiator divided by the baseline cycle length. RESULTS: Sixty-three VT events in
      14 patients met the inclusion criteria. A VPB initiated the VT in 58 episodes
      (92%), 1 episode (2%) was initiated by a supraventricular tachycardia, and 4
      episodes (6%) were sudden onset. The prematurity ratio was significantly higher
      (P < 0.05) in patients with ischemic cardiomyopathy (0.751 +/- 0.068) as compared
      to patients with nonischemic cardiomyopathy (0.604 +/- 0.139). CONCLUSION: VPBs
      initiated most sustained VT episodes. A significantly higher prematurity ratio
      was observed in the ischemic heart disease group. This may represent different
      mechanisms of VT initiation in patients with ischemic versus nonischemic heart
      disease.

PMID- 16630085
TI  - Atrial near-field and ventricular far-field analysis by automated signal
      processing at rest and during exercise.
AB  - INTRODUCTION: Sophisticated monitoring of atrial activity is a prerequisite for
      modern pacemaker therapy. Ideally, near-fields and ventricular far-fields ought
      to be distinguished by beat-to-beat template analysis of the atrial signal. A
      prerequisite is that atrial signals are stable under different conditions.
      METHODS AND RESULTS: A Matlab routine was developed to analyze atrial
      electrograms of 23 patients at least 3 months after implantation of a dual
      chamber pacemaker under several conditions including at rest, bipolar at rest, in
      an upright position, during treadmill exercise, and postexercise. A near-field
      and far-field template was created and amplitudes, widths, and slew rates were
      measured. In bipolar configuration, near-field amplitude at rest was 3.04 +/-
      0.94 mV (unipolar)/3.36 +/- 1.0 mV (bipolar) versus 3.18 +/- 1.0 mV (bipolar) at
      peak exercise. Far-field amplitude at rest was 1.66 +/- 1.18 (unipolar)/0.47 +/-
      0.27 mV (bipolar) and 0.41 +/- 0.21 mV (bipolar) at peak exercise (n.s. for
      bipolar measurements). No overall significant changes were observed for near- and
      far-field widths and slew rates during exercise. Shorter tip-ring distances of
      the atrial bipole, lead position, and the presence of sinus node disease did not
      have any impact on overall near- and far-field signal characteristics.
      Intraindividual differences between rest and peak exercise were moderate (range:
      near-field +0.15 to -0.54 mV; range: far-field +0.05 to -0.18 mV). CONCLUSIONS:
      Atrial near and far fields can be automatically classified and quantified by
      automated signal processing. Signals did not change during exercise or change of
      posture. This is a prerequisite for the implementation of beat-to-beat template
      analysis into pacemakers.

PMID- 16630086
TI  - QT dispersion increases with aging.
AB  - BACKGROUND: Age-related changes in cardiovascular system are well-known.
      Arrhythmias in elderly patients constitute most of the urgencies, consultations,
      or hospitalizations. QT dispersion (QTd) is a simple noninvasive arrhythmogenic
      marker to demonstrate the electrical instability of the heart. The aim of this
      study was to investigate how QTd changes with increasing age by calculating the
      QTd in the elderly and younger subjects. METHODS: One hundred and forty-six
      consecutive subjects (62 males and 84 females; age range: 18-82 years) were
      enrolled in the study. Sixty-seven of the subjects were 65 years and over (mean
      age, 70 +/- 4), 79 were younger than 65 (mean age, 37 +/- 11). A 12-lead ECG was
      recorded. The longest and the shortest QT intervals were measured manually on
      these ECG recordings. QTd was calculated from the formula, QTd = QTmax - QTmin.
      RESULTS: Demographic features were similar between the two groups. QTd of the
      elderly group was found to be significantly higher than the younger group (35.6
      +/- 15.6 in elderly, 24.2 +/- 12.4 in younger group, P < 0.001). A positive
      relationship was found between QTd and age (r = 0.415, P < 0.001). QTd was
      greater in female than in male (31.9 +/- 16.7 ms vs 26.0 +/- 11.3 ms,
      respectively, P = 0.018). CONCLUSIONS: Our study shows that QTd increases with
      advancing age. We think that long-term follow-up of these patients would be
      useful to show if there is any relationship between the clinical outcomes and the
      increase in QTd.

PMID- 16630087
TI  - Fragmented left sided QRS in absence of bundle branch block: sign of left
      ventricular aneurysm.
AB  - BACKGROUND: A left ventricular aneurysm (LVA) occurs between 3.5% and 9.4% of all
      cases of acute myocardial infarction. A fragmented left sided QRS (RSR; pattern
      or its variant RSr;, rSR;, or rSr;) without evidence of bundle branch block (QRS
      duration <or=120 ms) on the ECG may be associated with a significant myocardial
      scar, which is the characteristic of a LVA. We, therefore, postulate that
      fragmented QRS (RSR; pattern or its variant) in the left sided leads (I, aVL,
      V(3) to V(6)) may be a useful sign of LVA. METHODS: ECGs of 110 consecutive
      patients with LVA documented by left ventricular angiography (30 degrees right
      anterior oblique view) was compared with 220 patients without LVA (110 patients
      with and 110 patients without coronary artery disease (CAD)), who were evaluated
      for CAD by symptoms and signs. RESULTS: The sensitivity of the fragmented QRS for
      identification of LVA was 50% (55 of 110 patients) and specificity was 94.6% (209
      of 220). Within the study population, the positive predictive value of the
      fragmented QRS for LVA was 83.3% (55 of 66) and the negative predictive value was
      79.2% (209 of 264). Based on the range of prevalence of LVA in postmyocardial
      infarction population (3.5-9.4%) and on observed sensitivity and specificity, the
      positive predictive value of fragmented QRS for LVA after infarction can be
      estimated at 29-53% and the negative predictive value can be estimated at 95-98%.
      CONCLUSION: The sensitivity of fragmented QRS in left precordial leads for LVA
      was only 50%, whereas the specificity was 94.5%. It has a relatively low to
      moderate positive predictive value and high negative predictive value.

PMID- 16630088
TI  - Patterns of atrial fibrillation after coronary artery bypass surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia occurring in
      patients after coronary artery bypass surgery (CABG). The purpose of this study
      was to determine whether AF characteristics were independently associated with
      postoperative length of stay (LOS). METHODS: Two hundred ninety consecutive post
      CABG patients were examined through a detailed chart review. Baseline,
      intraoperative, and postoperative variables and the characteristics of AF were
      recorded. AF episodes were divided into single episodes lasting less than 24
      hours (short-lived AF) and recurrent or prolonged >or=24 hours of AF
      (recurrent/prolonged AF). RESULTS: AF occurred in 94 (32.4%) patients. Twenty-six
      (27.7%) of AF patients had short-lived AF, and 68 (72.3%) of AF patients had
      recurrent/prolonged AF. Patients with recurrent/prolonged AF were older (P <
      0.001) and more likely to have a history of prior AF (P < 0.001) relative to the
      other groups. Short-lived AF did not prolong LOS (7.2 +/- 2.1 days) relative to
      patients without AF (7.5 +/- 3.9 days), whereas recurrent/prolonged AF
      significantly prolonged LOS (10.4 +/- 6.1 days, P < 0.001). Multivariate analysis
      identified postoperative complications, recurrent/prolonged AF, age, and digoxin
      use as independent predictors of LOS. Recurrent/prolonged AF contributed an
      additional 1.1 days to LOS after adjusting for baseline clinical differences.
      CONCLUSIONS: There are heterogenous patterns of AF after cardiac surgery. A
      substantial minority of AF is short-lived and isolated with no impact on LOS;
      however, recurrent or prolonged AF significantly affects LOS.

PMID- 16630089
TI  - Abnormalities in fractal heart rate dynamics in Chagas disease.
AB  - BACKGROUND AND METHODS: In order to study fractal HR dynamics in Chagas disease,
      we performed detrended fluctuation analysis (DFA)-along with analysis of power
      law beta slope (beta index) and standard deviation of N-N intervals (SDNN)-in
      edited and unedited (with ventricular premature beats - VPBs, only in DFA
      analysis) series of R-R intervals from Holter monitoring of healthy controls
      (Group 0, n = 27) and Chagas disease patients with left ventricular (LV) ejection
      fraction >50% (Group 1, n = 137) and with LV ejection fraction <50% (Group 2, n =
      23). RESULTS: When analyzed from the edited R-R interval data, the long-term
      scaling exponent alpha(2) is altered both among the Chagas patients with and
      without LV dysfunction. The short-term scaling exponent alpha(1) was higher in
      Group 1 Chagas patients as compared to controls (P < 0.01) and did not differ
      between Group 2 and controls. In unedited R-R interval series, alpha(1) was
      significantly reduced in Group 2 Chagas patients (0.55 +/- 0.002) as compared to
      controls (0.90 +/- 0.002) and Group 1 (0.91 +/- 0.003) (P < 0.001), but did not
      differ between Group 1 and controls. Similarly alpha(2) was lower in Group 2
      compared to other groups (P < 0.001). SDNN did not differ between the groups, but
      the beta index derived from 1/f model was reduced both in Group 1 and 2 Chagas
      patients as compared to controls (P < 0.01). There was strong correlation (rs =
      0.82; P < 0.001) between the beta and alpha(2) index from edited series. There
      was an inverse correlation (rs =-0.63, P < 0.01) between the number of VPBs and
      alpha(1) index of unedited series. CONCLUSIONS: The long-term fractal HR dynamics
      altered in chagasic patients with and without LV dysfunction could be an early
      sign of autonomic dysfunction. Patients with impaired LV function show marked
      alterations in short-term fractal HR dynamics toward more random behavior, mainly
      due to frequent ectopy. Prospective studies are necessary to define the value of
      these indices as predictors of death in Chagas disease.

PMID- 16630090
TI  - The relationship between heart rate recovery and heart rate variability in
      coronary artery disease.
AB  - BACKGROUND: Reduced heart rate recovery (HRR) in coronary artery disease (CAD) is
      predictive of increased cardiovascular mortality and is related to reduced
      parasympathetic tonus. OBJECTIVE: To investigate HRR and heart rate variability
      (HRV) measured at steady state condition and the relationship between these two
      parameters in CAD. MATERIALS AND METHODS: In our study, we enrolled 33 (28 males,
      mean age 52.4 +/- 9.6 years) patients with CAD who did not have heart failure,
      atrial fibrillation, pacemaker, and any disease state that could affect the
      autonomic functions and 38 age-matched healthy subjects (21 males, mean age 48.3
      +/- 7.8 years). All the patients underwent submaximal treadmill exercise testing
      (Bruce protocol). HRR was calculated by subtracting the heart rate values at the
      1st, 2nd, and 3rd minutes of the recovery phase from the peak heart rate (HRR(1),
      HRR(2), HRR(3)). Before exercise testing, short-term steady state HRV analyses of
      all subjects were obtained with the time- and frequency-domain methods and were
      correlated to HRR. For frequency-domain analysis, low-frequency HRV (LF, 0.004
      0.15 Hz), high-frequency HRV (HF, 0.15-0.5 Hz), and LF/HF ratio were measured for
      5 minutes in the morning. For time-domain analysis, standard deviation of the
      normal-to-normal NN intervals (SDNN), square root of the mean squared differences
      of successive N-N intervals (RMSSD), and proportion derived by dividing the
      number of interval differences of successive N-N intervals greater than 50 ms by
      the total number of N-N intervals (pNN50) were obtained. Only HRR(3) was used for
      the correlation analysis. RESULTS: In CAD groups, the HF, an indicator of
      parasympathetic activation, was significantly reduced, whereas the LF and LF/HF
      values, which are indicators of sympathetic activity, were increased (P = 0.0001
      for each parameter). The time-domain parameters SDNN, RMSSD, and pNN50 were
      significantly reduced in the patient group (P = 0.0001, P = 0.009, and P =
      0.0001, respectively). Similar to the HRV parameters, the HRR(1), HRR(2), and
      HRR(3) values were significantly reduced in the patient group (P = 0.0001 for
      each parameter). We observed a significant negative correlation between HRR(3)
      and LF (r =-0.67, P = 0.0001) and between HRR(3) and LF/HF (r =-0.62, P <
      0.0001), while there was a significant positive correlation between HRR(3) and
      HF, SDNN, RMSSD, and pNN50 (r = 0.69, P = 0.0001; r = 0.41, P = 0.0001; r = 0.31,
      P = 0.008; and r = 0.44, P = 0.0001). CONCLUSIONS: HRR and HRV are significantly
      reduced in CAD. The reduction in HRR is parallel to the changes in HRV
      parameters. HRR, which can be measured easily in the recovery phase of exercise
      testing, can be used to detect the depression of parasympathetic tonus and to
      evaluate the basal autonomic balance in this patient group.

PMID- 16630091
TI  - An evaluation of the impact of oral magnesium lactate on the corrected QT
      interval of patients receiving sotalol or dofetilide to prevent atrial or
      ventricular tachyarrhythmia recurrence.
AB  - BACKGROUND: Intravenous magnesium reduces the QTc interval of patients receiving
      ibutilide. Whether oral magnesium can reduce the QTc interval associated with
      oral sotalol and dofetilide is not known. This study was undertaken to evaluate
      the impact of oral magnesium on the QTc interval and whether an inherent
      intracellular magnesium deficiency exists among patients with arrhythmias.
      METHODS: Participants receiving sotalol or dofetilide for atrial or ventricular
      arrhythmias were randomized to receive magnesium l-lactate (504 mg elemental
      magnesium daily, Niche Pharmaceuticals, Roanoke, TX) or placebo for 48 hours. A
      12-lead electrocardiogram (ECG) was obtained at baseline, 3 hours, and 51 hours
      after dosing to correspond to the Tmax after oral ingestion. The QTc interval was
      measured from the ECGs and compared between groups. Intracellular magnesium
      concentrations were determined by energy-dispersive x-ray analysis at baseline
      and 51 hours after dosing (Intracellular Diagnostics, Inc., Foster City, CA).
      RESULTS: The QTc interval reductions from baseline were greater in the magnesium
      group than placebo at 3 and 51 hours (P = 0.015 and P < 0.001, respectively).
      Sixty-three percent of patients (regardless of experimental group) had baseline
      intracellular magnesium concentrations below the normal reference range of 33.9
      41.9 mEq/IU, with an average level of 32.6 +/- 2.2 mEq/IU. CONCLUSIONS: Oral
      magnesium l-lactate raises intracellular magnesium concentrations and lowers the
      QTc interval of patients receiving sotalol or dofetilide.

PMID- 16630092
TI  - Implication from randomized trials of rate and rhythm controls on management of
      patients with persistent atrial fibrillation.
AB  - Recently, several randomized trials were published on the issue of rate or rhythm
      control for patients with atrial fibrillation (AF). Patients were typically minor
      symptomatic, relatively old, with age above 70, presenting with a recurrence of
      AF and suffering from only mild to moderate underlying heart disease. The main
      outcome of these trials is that rate control is not inferior to rhythm control
      for the management of patients with AF concerning morbidity and mortality. Also
      patients' quality of life did not differ significantly in follow-up in these
      trials. However, rhythm control is not redundant in the treatment of AF. Focus is
      now on subgroups of patients who could still have benefit being in sinus rhythm.
      For severely symptomatic patients, patients presenting with the first episode of
      AF and probably those with severe congestive heart failure, to restore and
      maintain sinus rhythm should still be the goal. With the failure of
      antiarrhythmic therapy, nonpharmacological approaches such as pulmonary vein
      isolation can be performed. Another finding of the randomized trials is that
      being in sinus rhythm does not prevent from the occurrence of thromboembolic
      complications. This means that for patients with AF, with risk factors for
      thromboembolic events, adequate anticoagulant therapy is indicated irrespective
      of the current heart rhythm. As with antiarrhythmic therapy, the search for new
      and safer anticoagulant therapy is underway. This review will focus on the key
      aspects we have learned from the randomized trials on rate and rhythm controls
      for patients with AF.

PMID- 16630093
TI  - The year 2005 in electrocardiology.

PMID- 16630094
TI  - Right ventricular infarction mimicking anterior infarction.
AB  - It is rare to observe ST elevation in anterior derivations caused by right
      ventricular branch occlusion. We described the case of a patient with unstable
      angina who developed acute right ventricular myocardial infarction with ST
      segment elevation in anterior precordial leads (V(1)-V(4)) shortly after coronary
      angiography. Coronary angiogram revealed total occlusion of the right coronary
      artery (RCA) proximally to the right ventricular branch. This reminds us that the
      presence of diffuse ST-segment elevation in the precordial leads could be due to
      acute RCA occlusion. The differentiation of these two entities is important, as
      their therapies are quite different.

PMID- 16630095
TI  - R wave increases after hemodialysis revisited.

PMID- 16630096
TI  - Scientific misconduct, stem cells, and the way ahead.

PMID- 16630097
TI  - Best-practice algorithms for the use of a bilayered living cell therapy
      (Apligraf) in the treatment of lower-extremity ulcers.
AB  - Tissue-engineered skin substitutes such as Apligraf have emerged over the past 20
      years as among the most carefully studied and efficacious of the advanced wound
      modalities. These products have been proven as effective enhancements to general
      wound care, promoting wound closure particularly in instances where conventional
      wound care fails. Marketed for hard-to-heal wounds since 1998, Apligraf has
      become part of standard wound care in many wound centers across the United
      States. Despite this situation, few general wound care guidelines incorporate
      advanced and active wound-healing technologies, such as tissue-engineered skin
      products. Because of this deficiency, appropriate patient selection and proper
      use of these product remain largely unaddressed within the general wound care
      community. Here, we describe the development of guidelines surrounding optimal
      use of the bilayered living cell therapy, Apligraf, in the treatment of the two
      types of lower extremity ulcers for which the product is FDA approved: venous leg
      ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on
      the identification and selection of patients who are at risk for failure of
      standard wound care therapy and thus appropriate for Apligraf treatment. The
      intended audience for these guidelines is the general wound care practitioner,
      for whom the developed treatment algorithms and accompanying figure legends
      should provide practical, user-friendly direction simplifying both patient
      selection and appropriate use of Apligraf within the context of good wound
      healing practice.

PMID- 16630098
TI  - Assessment of health-related quality of life in patients with lymphedema of the
      lower limb.
AB  - The purpose of this study was to examine the use of a number of tools in the
      evaluation of health-related quality of life in patients with lower limb
      lymphedema, and to determine the consequences of cancer history and concurrent
      leg ulceration. Patients in one health trust having lower limb lymphedema were
      identified and interviewed at entry and after 24 weeks. The short form-36 (SF
      36), modified Barthel scale, McGill short form pain questionnaire, and Euroqol
      were administered at both time points. Of the 164 (median age=76.9 years, 70.7%
      women) patients who comprised the study population, 15.2% had a history of cancer
      and 30.4% had coexisting current leg ulceration. Internal consistencies were high
      for all scales (Cronbach's alpha >0.80). There were high ceiling effects for a
      number of SF-36 scores, and high floor effects in these and the McGill short form
      pain questionnaire, scales. Despite these limitations, there was strong evidence
      that treatment led to significant improvements in six of eight scores of the SF
      36, three of three scores of the McGill short form pain questionnaire and the
      modified Barthel scale (all p<0.05). The improvement in physical functioning was
      significantly greater for patients who entered the study with a leg ulcer (mean
      different=9.1, 95% confidence interval 2.1-16.1, p=0.011). Patients treated with
      compression bandaging had significantly greater improvements for physical
      functioning (10.2) than those treated with compression hosiery (-1.5) or no
      treatment (-2.0), p=0.001. Of the tools assessed, the SF-36, appears to be the
      most appropriate for use in this patient group.

PMID- 16630099
TI  - Low serum zinc level as a predictive factor of delayed wound healing in total hip
      replacement.
AB  - Delayed wound healing after total arthroplasty puts the patient at risk for
      superficial and deep infection, with substantial economic and social
      consequences. The objective of this study was to assess serum zinc levels as a
      tool for predicting such a delay in patients with primary osteoarthritis or
      osteoarthritis secondary to avascular necrosis. We conducted a prospective study
      of 80 total hip arthroplasties, analyzing possible correlations between delayed
      healing and serum zinc, nutritional parameters, and other demographic and
      epidemiological variables. The predictive value of preoperative serum zinc levels
      and lymphocyte counts was confirmed; thus, an arthroplasty procedure could be
      timed to minimize risk.

PMID- 16630100
TI  - Mactinin treatment promotes wound-healing-associated inflammation in urokinase
      knockout mice.
AB  - Mactinin, a 31 kDa fragment from the amino-terminal end of alpha-actinin, is
      chemotactic for monocytes and can promote monocyte/macrophage maturation.
      Macrophages are essential for wound healing, in which they play key roles in
      debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We
      have previously determined that urokinase is necessary to form mactinin from
      extracellular alpha-actinin, which may be present at sites of inflammation as a
      result of cell movement. Thus, urokinase knockout mice are unable to form
      mactinin and therefore are an ideal model to study mactinin's effects on wound
      healing. Saline- and mactinin-treated wounds were analyzed in a subcutaneous
      sponge wound model in both wild-type and urokinase knockout mice. The wounded
      urokinase knockout mice had markedly decreased leukocyte infiltration compared
      with wounded wild-type mice. In addition, production of the proinflammatory
      cytokine, interleukin-12, and of collagen was also decreased in knockouts.
      Treatment of knockout mice with mactinin resulted in leukocyte infiltration
      numbers, interleukin-12 levels, and hydroxyproline measurements similar to those
      in wild-type mice. The results suggest that impaired wound healing in urokinase
      deficient mice can be restored by administration of mactinin.

PMID- 16630101
TI  - In vivo delivery of heat shock protein 70 accelerates wound healing by up
      regulating macrophage-mediated phagocytosis.
AB  - Injury causes tissue breakdown, which releases large quantities of intracellular
      contents into the extracellular space. Some of these materials are well
      established activators of the immune system and include heat shock proteins
      (HSPs), uric acid, nucleotides, High Mobility Group Box-1 protein (HMGB-1), and
      DNA. Here, we show that in vivo delivery of HSPs into BALB/cJ mice with full
      thickness wounds accelerates the rate of wound closure by 60% as compared with
      control-treated mice. The onset is rapid and the effect is sustained, dose
      dependent, and protein specific. Adoptive transfer of RAW264 macrophages
      pretreated with HSP70 into naive recipients with a wound transfers the HSP
      mediated effect on the rate of wound closure. Further, we demonstrate that part
      of the mechanism by which HSP70 accelerates wound closure is through the
      stimulation of macrophage-mediated phagocytosis of wound debris. Disabling the
      HSP70-mediated enhancement of phagocytosis abrogates the HSP-mediated
      acceleration of the healing process. These findings create two opportunities:
      one, therapeutic, wherein HSP70 could be used in the clinical management of
      wounds; and two, pathophysiologic, to decode signals by which the host defenses
      recognize and respond to injury.

PMID- 16630102
TI  - Inhibition of procollagen C-proteinase reduces scar hypertrophy in a rabbit model
      of cutaneous scarring.
AB  - Hypertrophic scarring, which results from excessive collagen deposition at sites
      of dermal wound repair, can be functionally and cosmetically debilitating to the
      surgical patient. Pharmacological regulation of collagen synthesis and deposition
      is a direct approach to the control of scar tissue formation. One of the key
      steps in collagen stabilization is the cleavage of the C-terminal propeptide from
      the precursor molecule to form collagen fibrils, a reaction catalyzed by
      procollagen C-proteinase (PCP). We tested the ability of a PCP inhibitor to
      reduce hypertrophic scar formation in a rabbit ear model. After the placement of
      four, 7-mm dermal wounds on each ear, New Zealand white rabbits received PCP
      inhibitor subcutaneously in the left ear at four time points postwounding: days
      7, 9, 11, 13 (early treatment; n=20 wounds) or days 11, 13, 15, 17 (late
      treatment; n=20 wounds). The right ear of each animal served as a control
      (vehicle alone). Wounds were harvested on postoperative day 28 and scar
      hypertrophy quantified by measurement of the scar elevation index. Early
      treatment of wounds with PCP inhibitor did not reduce scar formation compared
      with controls (p>0.05). However, late treatment resulted in a statistically
      significant reduction in the scar elevation index (p<0.01). Our results point not
      only to the potential use of PCP inhibitors to mitigate hypertrophic scarring but
      also to the temporal importance of drug delivery for antiscarring therapy.

PMID- 16630103
TI  - Effect of extracts from the Chinese and European mole cricket on wound
      epithelialization and neovascularization: in vivo studies in the hairless mouse
      ear wound model.
AB  - Until the end of World War II, oily extracts from the European mole cricket,
      Gryllotalpa gryllotalpa Linne, were used for treating nonhealing wounds and
      burns. In traditional Chinese medicine, extracts from the Chinese mole cricket,
      Gryllotalpa africana Beauvois, have been used to treat boils, abscesses, and
      ulcers successfully for over two centuries and are still being used today. The
      aim of this study was twofold: first, to measure the effect mole cricket extracts
      have on wound epithelialization and neovascularization, and second, to identify
      the active compounds in the Chinese and German mole cricket extracts. For the
      first aim, the hairless mouse ear wound model was used. The findings showed that
      wounds treated with the mole cricket extracts epithelialized significantly faster
      than control wounds 12.7+/-0.9 and 13.2+/-1.4 days vs. 16.3+/-2.2 days (mean+/
      SD, p<0.05), respectively. While the rate of wound neovascularization was
      significantly increased in the first 3 days postwounding from that point on, the
      rate in treated wounds was the same as in controls. To identify the active
      compounds in the mole cricket extracts, the extracts were fractionated and tested
      in a foreskin basal keratinocyte cell culture assay. In this assay, the migration
      of keratinocytes is similar to skin cell migration or reepithelialization in a
      healing wound. Using this method, we found the active compound in the mole
      cricket extracts to be linoleic acid methyl ester. All other fatty acid
      structures that were isolated were found to be inactive.

PMID- 16630104
TI  - Purinergic substances promote murine keratinocyte proliferation and enhance
      impaired wound healing in mice.
AB  - As membrane-bound receptors for adenosine, purines, and pyrimidines,
      purinoceptors are expressed in nearly all cell types throughout the mammalian
      organism. Previous studies showed that purinoceptors are involved in the
      regulation of proliferation and differentiation of most target cells. The present
      study was performed to elucidate their role in keratinocyte proliferation and
      wound healing. The expression of the mRNA of several adenosine and P2Y receptors
      was shown in the immortalized murine keratinocyte cell line MSC-P5 and primary
      cultured keratinocytes of four different mouse strains. The nonselective
      adenosine receptor agonist 5'-(N-ethyl)-carboxamidoadenosine enhanced the growth
      of MSC-P5 cells in vitro via the A2B receptor. The proliferative stimulus of
      adenosine triphosphate and uridine triphosphate on this cell line was mediated by
      the P2Y2 receptor. The mitogenic effect of the purinergic substances was
      inhibited by simultaneous treatment with respective antagonists. Studies in a
      mouse model of dexamethasone-induced impaired wound healing showed the in vivo
      efficacy of the purinoceptor agonists. These studies confirm that pharmacological
      actions via purinoceptors offer an intriguing possibility in the treatment of
      impaired wound healing. Nevertheless, further investigations are needed to
      elucidate fully the role of purinergic mechanisms involved in wound healing.

PMID- 16630105
TI  - Expression and possible mechanism of c-ski, a novel tissue repair-related gene
      during normal and radiation-impaired wound healing.
AB  - C-ski is a complicated regulating factor for fibroblast proliferation and an
      important co-repressor of Smad3. Although inhibiting Smad3 activity can markedly
      promote wound healing because Smad3 mediates the role of transforming growth
      factor-beta in inhibiting cell proliferation and inducing cell apoptosis; there
      has been no report on whether c-ski is expressed during wound healing and the
      relationship between its expression and wound healing. By establishing animal
      models of normal and radiation-impaired wound healing and using
      immunohistochemistry, in situ hybridization, and reverse transcription-polymerase
      chain reaction, we found that c-ski was expressed after wounding and reached its
      peak on day 9 and then significantly decreased. C-ski was present in all repair
      cells, and was especially prominent in fibroblasts. Compared with the control
      side, the irradiated side showed a lower expression of c-ski on postwound days 3
      9, but higher on day 15, and not significantly different after the wound was
      healed. The expression of Smad3 was in contrast to the c-ski and cellular
      proliferation was similar to that of c-ski expression. The apoptosis index was
      significantly higher on the irradiated side on days 3-9 compared with the control
      side. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      results showed that c-ski could reverse the inhibitory role of Smad3 on
      fibroblast proliferation. Flow cytometry analysis found that c-ski also
      diminished fibroblast apoptosis induced by Smad3 transfection. These results
      suggest that there is not only obvious expression of this regulatory protein but
      there is also a significant change in the levels of c-ski during wound healing.
      Its in vivo expression pattern and experiments in vitro suggest that c-ski may be
      involved in tissue repair by repressing Smad3 activity. Radiation can reduce c
      ski and increase Smad3 expression, resulting in elevated Smad3 activity,
      resulting in diminished cell proliferation, cell apoptosis, and wound-healing
      delays.

PMID- 16630106
TI  - Phenotypic differences between oral and skin fibroblasts in wound contraction and
      growth factor expression.
AB  - Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring
      compared with cutaneous wounds. The differences in healing outcome between oral
      mucosa and skin could be because of phenotypic differences between the respective
      fibroblast populations. This study compared paired mucosal and dermal fibroblasts
      in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha
      SMA), and production of the epithelial growth factors: keratinocyte growth factor
      (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of
      transforming growth factor -beta1 and -beta3 on each parameter were also
      determined. Gel contraction in floating collagen lattices was determined over a 7
      day period. alpha-SMA expression by fibroblasts was determined by Western
      blotting. KGF and HGF expression were determined by an enzyme-linked
      immunosorbent assay. Oral fibroblasts induced accelerated collagen gel
      contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells
      also produced significantly greater levels of both KGF and HGF than their dermal
      counterparts. Transforming growth factor-beta1 and -beta3, over the concentration
      range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel
      contraction and alpha-SMA production, but inhibiting KGF and HGF production by
      both cell types. These data indicate phenotypic differences between oral and
      dermal fibroblasts that may well contribute to the differences in healing outcome
      between these two tissues.

PMID- 16630107
TI  - Serum-dependent effects on adult and fetal tendon fibroblast migration and
      collagen expression.
AB  - Cell migration and extracellular matrix synthesis play an important role in the
      wound-healing response to injury. Several studies have described differences in
      migratory behavior and collagen biosynthetic activity in adult vs. fetal skin
      fibroblasts. The objective of this study was to examine the serum- and age
      dependent effects on cell migration and collagen expression in tendon
      fibroblasts. Medial tendon fibroblasts were isolated from pregnant ewes and their
      fetuses, and cultured with and without serum for up to 7 days. Cell migration was
      determined by quantitative image analysis, and collagen expression was assessed
      by reverse transcription-polymerase chain reaction and immunohistochemical
      staining. In serum-containing medium, tendon fibroblasts migrated significantly
      faster than cells in serum-free medium. Additionally, fetal tendon fibroblasts
      migrated significantly faster than adult tendon fibroblasts under both culture
      conditions. The expression of types I and III collagen mRNA was significantly up
      regulated in tendon cell populations in serum-free medium compared with those in
      serum-containing medium. Quantitative assessment of collagen staining indicated
      that fetal tenocytes produced more type I collagen than adult tenocytes under
      both culture conditions. These findings suggest that there is an inherent
      difference between adult and fetal tendon fibroblasts, which may have
      implications in the wound-healing response in tendons.

PMID- 16630108
TI  - Response of human peritoneal mesothelial cells to inflammatory injury is
      regulated by interleukin-1beta and tumor necrosis factor-alpha.
AB  - Peritoneal injury is often associated with alterations of the mesothelium,
      resulting in peritoneal healing and adhesion formation. We analyzed the effects
      of pro-inflammatory cytokines on cell morphology and proliferation of human
      peritoneal mesothelial cells (HPMC). After 48 hours, HPMC formed a confluent
      layer with cell volumes of 2,662+/-111 fL. Treatment of HPMC with interleukin
      1beta and tumor necrosis factor-alpha (TNF-alpha) induced mesothelial
      disintegration and alterations in mesothelial cell morphology, which were
      associated with an interleukin-1beta-triggered increase in cell volume (3,028+/
      118 fL; p<0.05) and exfoliation of cells into the supernatants of cell cultures
      (p<0.05). Whereas TNF-alpha arrested HPMC in the G0/G1 phase (p<0.05),
      interleukin-1beta caused an increase of cells into the S phase of the cell cycle.
      In addition, interleukin-1beta and interferon-gamma exerted a proliferative
      effect on HPMC. These changes were independent from mesothelial Na+/H+ antiporter
      1 expression. Our data indicate that the response of HPMC to inflammatory injury
      is regulated by interleukin-1beta and TNF-alpha reflecting their putative role in
      peritoneal wound healing and adhesion formation.

PMID- 16630109
TI  - Effect of platelet-rich plasma on migration and proliferation of SaOS-2
      osteoblasts: role of platelet-derived growth factor and transforming growth
      factor-beta.
AB  - Platelet-enriched plasma (PRP) is used in therapy as a source of growth factors
      in bone fracture and wound healing; however, few data exist on its role in the
      different aspects of the healing process. The effect of PRP and of the two main
      growth factors present in this preparation (platelet-derived growth factor [PDGF]
      and transforming growth factor-beta [TGF-beta]) was evaluated in vitro using the
      human osteoblastic cell line SaOS-2, which was shown by reverse transcription
      polymerase chain reaction to express both PDGF-alpha and -beta receptors.
      Batroxobine-activated PRP was added in different concentrations to SaOS-2 cells
      to assess cell migration (by a microchemotaxis assay) and cell proliferation (by
      [3H]-thymidine incorporation into the DNA). Immunoneutralization with anti-PDGF
      beta or anti-TGF-beta antibodies allowed the assessment of the specific role of
      these growth factors. The overall results obtained indicate that PRP dose
      dependently stimulates both chemotaxis and cell proliferation. PDGF and TGF-beta
      appear to exert distinct effects on the two parameters, the former involved in
      stimulating cell migration and the latter in inhibiting cell proliferation. It is
      concluded that the different growth factors present in activated PRP can
      specifically contribute to the main processes of tissue regeneration.

PMID- 16630110
TI  - Use of an in vitro model of tissue-engineered human skin to study keratinocyte
      attachment and migration in the process of reepithelialization.
AB  - To produce a stable epidermis, keratinocytes need to be firmly attached to the
      basement membrane. However, following wounding, keratinocytes are required to
      develop a migratory phenotype in order to reepithelialize the wound. To
      investigate some of the issues underlying reepithelialization, we have developed
      a three-dimensional in vitro model of tissue-engineered skin, comprising
      sterilized human dermis seeded with human keratinocytes and dermal fibroblasts.
      Using this model, we have shown that the inclusion of fibroblasts within the
      model increases the stability of keratinocyte attachment. We have also
      demonstrated that keratinocyte migration occurs most effectively in the absence
      of a basement membrane and following the inclusion of fibroblasts in the model.
      In addition, subjecting the keratinocyte layer to mechanical trauma induces a
      migratory phenotype. We conclude that this three-dimensional in vitro wound model
      can be used to increase our understanding of the factors that enhance
      keratinocyte migration and hence wound healing in vivo.

PMID- 16630111
TI  - Effect of Vacuum Assisted Closure Therapy on early systemic cytokine levels in a
      swine model.
AB  - Vacuum Assisted Closure (V.A.C.) Therapy has previously been shown to facilitate
      healing of wounds. However, the physiological mechanism(s) of this treatment
      modality and its systemic effects require further investigations. The goal of
      this porcine study was to investigate the effect of V.A.C. Therapy on the
      systemic distribution of the inflammatory cytokines interleukin (IL)-6, IL-8, IL
      10, and transforming growth factor-beta1. Twelve pigs were each given one full
      thickness excisional wound, using electrocautery. Six of the pigs were treated
      with V.A.C. Therapy and six with saline-moistened gauze. Serum samples were
      collected immediately after wound creation, and hourly for 4 hours. Samples were
      analyzed using commercially available enzyme-linked immunosorbent assay kits.
      During the initial 4 hours of treatment, V.A.C. Therapy resulted in earlier and
      greater peaking of IL-10 and maintenance of IL-6 levels compared with saline
      moistened gauze controls, which showed decreased IL-6 values over the first hour
      (both at p<0.05). No other treatment-based differences were detected.

PMID- 16630112
TI  - Muscle-derived stem cells used to treat skin defects prevent wound contraction
      and expedite reepithelialization.
AB  - Stem cells derived from adult tissues may serve as cell therapy to enhance the
      healing process in skin wounds. This study was designed to evaluate the use of
      autologous muscle-derived stem cells in an experimental skin wound model in terms
      of their efficiency at promoting tissue repair/regeneration. Muscle-derived cells
      obtained from the dorsal muscle of New Zealand rabbits were cultured in vitro for
      2 weeks. The cell population was identified using the satellite markers CD34, m
      cadherin and Myf5, and the proliferative capacity of the adult stem cells was
      determined. The population was then fluorescently labeled with PKH26 and seeded
      onto a circular 2 cm diameter defect created on the dorsal side of the ear of the
      rabbit from which the cells had been harvested. Similar defects on the contra
      lateral ears were left untreated to form the control group. Fourteen days later,
      specimens were taken for light, transmission, and scanning electron microscopy,
      as well as for immunolabeling with antibodies against vimentin, alpha-actin,
      desmin, myosin, fibronectin, and cytokeratin 14. Areas of wound contraction and
      reepithelialization were determined by image analysis. Wound contraction was
      significantly greater in the control than the treatment group (p<0.05); control
      specimens also showed more myosin expression. Reepithelialized areas were
      significantly greater in the treatment group (p<0.05). Control wounds showed
      nonepithelialized areas and inflammatory granulation tissue. Reepithelialization
      occurred as epidermal tongues of fusiform cells. Our findings indicate that the
      use of autologous stem cells on skin wounds expedites and improves the organism's
      natural healing process.

PMID- 16630113
TI  - Stem cells isolated from adult rat muscle differentiate across all three dermal
      lineages.
AB  - Adult stem cells capable of differentiating into phenotypes from all three dermal
      layers were isolated from adult rat muscle. Stem cells were obtained by enzymatic
      digestion, followed by primary culture in Eagle's minimum essential medium +10%
      preselected horse serum. When the cells reached confluence, they were released by
      trypsin, filtered to remove differentiated myotubes, and then slow frozen in 7.5%
      dimethylsulfoxide to -80 degrees C. Thawed cells were the stem cells and were
      induced to differentiate with the nonspecific differentiating agent dexamethasone
      at concentrations of 10(-10)-10(-6) M. After a 6-week treatment with
      dexamethasone, the cells were assayed by immunohistochemistry for phenotypes of
      the mesodermal, ectodermal, and endodermal lineages. Examples of mesodermal
      phenotypes identified were as follows: bone, cartilage, and skeletal, smooth, and
      cardiac muscle. Ectodermal phenotypes identified were as follows: neurons and
      oligodendrocytes. Hepatocyte phenotypes identified represented the endodermal
      lineage. All the phenotypes were observed only with treatment with dexamethasone.
      However, nestin was observed in the absence of dexamethasone and may be a marker
      for uncommitted pluripotent stem cells. The results show that adult muscle
      contains pluripotent stem cells capable of differentiating across all three
      dermal lineages. Such cells could be used in the context of tissue engineering.

PMID- 16630114
TI  - Trends in primary androgen depletion therapy for patients with localized and
      locally advanced prostate cancer: Japanese perspective.
AB  - It has been conventionally accepted that primary androgen depletion therapy
      (PADT) is effective only as a palliative treatment against localized prostate
      cancer (LPC) and locally advanced prostate cancer (LAPC), like its effect against
      advanced (metastatic) prostate cancer. In Japan, however, PADT has long been the
      treatment of choice for LPC and LAPC. The frequency of PADT being chosen to treat
      LPC and LAPC is also on the rise in clinical practice in the USA. Very little
      evidence to support this trend has so far been available. A study on the outcomes
      of endocrine therapy is currently being conducted in Japan by the Japanese
      Prostate Cancer Surveillance Group. Results of several domestic and overseas
      randomized trials have recently been published, and evidence for the efficacy of
      PADT in LPC and LAPC has been accumulating. The effectiveness of PADT in LAPC, in
      particular, is worthy of attention. There is a possibility that therapeutic
      strategies for LPC and LAPC may change dramatically in the near future.

PMID- 16630115
TI  - Inhibition of intestinal carcinogenesis by a new flavone derivative, chafuroside,
      in oolong tea.
AB  - A new flavone derivative, chafuroside, has been isolated as a strong anti
      inflammatory compound from oolong tea leaves, and its structure determined to be
      (2R,3S,4S,4aS,11bS)-3,4,11-trihydroxy-2-(hydroxymethyl)-8-(4-hydroxyphenyl)
      3,4,4a,11b-tetrahydro-2H,10H-pyrano[2',3':4,5]furo[3,2-g]chromen-10-one. To
      assess its potential to inhibit intestinal carcinogenesis, 2.5, 5 and 10 p.p.m.
      chafuroside was given in the diet to Apc-deficient Min mice for 14 weeks from 6
      weeks of age. Total numbers of polyps were reduced to 83, 73 and 56% of the
      control value, respectively. Moreover, dietary administration at 10 and 20 p.p.m.
      reduced azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) development in
      rats to 69% of the AOM-treated control value with the higher dose. Chafuroside
      associated toxicity was not observed at 2.5-10 p.p.m. in Min mice and 10-20
      p.p.m. in AOM-treated rats. These results suggest that chafuroside might be a
      good chemopreventive agent for colon cancer.

PMID- 16630116
TI  - Induction of centrosome amplification in p53 siRNA-treated human fibroblast cells
      by radiation exposure.
AB  - Centrosome amplification can be detected in the tissues of p53(-/-) mice. In
      contrast, loss of p53 does not induce centrosome amplification in cultured human
      cells. However, examination of human cancer tissues and cultured cells has
      revealed a significant correlation between loss or mutational inactivation of p53
      and occurrence of centrosome amplification, supporting the notion that p53
      mutation alone is insufficient to induce centrosome amplification in human cells,
      and that additional regulatory mechanisms are involved. It has recently been
      shown that gamma irradiation of tumor cells induces centrosome amplification.
      However, the precise mechanism of radiation-induced centrosome amplification is
      not fully understood. In the present study, CCD32SK diploid normal human
      fibroblasts were transfected transiently with short interfering RNA (siRNA)
      specific for human p53 (CCD/p53i). There was a small increase in the frequency of
      centrosome amplification in CCD/p53i cells (4.0%) without irradiation. In
      contrast, CCD/p53i cells after 5-Gy irradiation showed a marked increase in
      abnormal nuclear shapes and pronounced amplification of centrosomes (46.0%). At
      12 h after irradiation, irradiated CCD/p53i cells were arrested in G(2) phase. By
      laser scanning cytometry, abnormal mitosis with amplified centrosomes was
      observed frequently in the accumulating G(2)/M population at 48 h after
      irradiation. In the present study, we found that siRNA-mediated silencing of p53
      in normal human fibroblasts, together with DNA damage by irradiation, efficiently
      induced centrosome amplification and nuclear fragmentation, but these phenomena
      were not observed with either siRNA-mediated silencing of p53 or irradiation
      alone.

PMID- 16630117
TI  - Wilms' tumor gene WT1 17AA(-)/KTS(-) isoform induces morphological changes and
      promotes cell migration and invasion in vitro.
AB  - The wild-type Wilms' tumor gene WT1 is overexpressed in human primary leukemia
      and in a wide variety of solid cancers. All of the four WT1 isoforms are
      expressed in primary cancers and each is considered to have a different function.
      However, the functions of each of the WT1 isoforms in cancer cells remain
      unclear. The present study demonstrated that constitutive expression of the WT1
      17AA(-)/KTS(-) isoform induces morphological changes characterized by a small
      sized cell shape in TYK-nu.CP-r (TYK) ovarian cancer cells. In the WT1 17AA(
      )/KTS(-) isoform-transduced TYK cells, cell-substratum adhesion was suppressed,
      and cell migration and in vitro invasion were enhanced compared to that in mock
      vector-transduced TYK cells. Constitutive expression of the WT1 17AA(-)/KTS(-)
      isoform also induced morphological changes in five (one gastric, one esophageal,
      two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1
      isoforms other than the WT1 17AA(-)/KTS(-) isoform induced the phenotypic
      changes. A decrease in alpha-actinin 1 and cofilin expression and an increase in
      gelsolin expression were observed in WT1 17AA(-)/KTS(-) isoform-transduced TYK
      cells. In contrast, co-expression of alpha-actinin 1 and cofilin or knockdown of
      gelsolin expression by small interfering RNA restored WT1 17AA(-)/KTS(-) isoform
      transduced TYK cells to a phenotype that was comparable to that of the parent TYK
      cells. These results indicated that the WT1 17AA(-)/KTS(-) isoform exerted its
      oncogenic functions through modulation of cytoskeletal dynamics. The present
      results may provide a novel insight into the signaling pathway of the WT1 gene
      for its oncogenic functions.

PMID- 16630118
TI  - Expression patterns of polo-like kinase 1 in human gastric cancer.
AB  - Polo-like kinase 1 (PLK1) is centrally involved in the regulation of mitosis in
      normal and malignant cells. It is known that inhibition of PLK1 expression in
      vitro and in vivo leads to mitotic arrest, induction of apoptosis and suppression
      of tumor growth. In the present study, expression of PLK1 was investigated in
      paraffin tissue of 135 cases of gastric adenocarcinoma and in 46 corresponding
      lymph node metastases by immunohistochemistry. Expression data were correlated
      with clinicopathological parameters and patient survival. Seventy-three (54.1%)
      of 135 carcinomas showed an overexpression of PLK1 compared to normal gastric
      mucosa. Overexpression of PLK1 correlated positively with tumor stage, nodal
      status and diffuse growth pattern. PLK1 expression in the primary tumor did not
      differ from PLK1 expression in the corresponding lymph node metastases. PLK1
      expression was a significant prognostic factor in univariate but not in
      multivariate survival analysis. As a conclusion, upregulated PLK1 expression in
      gastric cancer correlates with a malignant tumor phenotype and has impact on
      patient prognosis. These data underscore the importance of PLK1 in gastric
      carcinogenesis and present a translational link for functional data into
      potential clinical use by defining PLK1 as an attractive protein for novel
      targeted chemotherapeutic approaches in gastric cancer.

PMID- 16630119
TI  - DMRT-1 expression during NEC8 human embryonic carcinoma cell differentiation.
AB  - To elucidate the relationship between dsx and mab-3 related transcription factor
      1 (Dmrt-1) and differentiation, alteration in mRNA levels during differentiation
      of NEC8 human embryonic carcinoma cells was investigated. After stimulation with
      50 nM phorbol 12-myristate 13-acetate (PMA), the cells differentiated into cells
      with mesenchymal characteristics and upregulated Dmrt-1 mRNA, possibly through
      the protein kinase C/mitogen-activated protein kinase/activated protein-1
      signaling pathway. Conversely, knockdown of Dmrt-1 by small interfering RNA
      resulted in cell morphology that was different from that after PMA treatment.
      These results indicated that Dmrt-1 expression was apparently associated with the
      differentiation of NEC8, and this cell line may be a helpful in vitro tool to
      clarify the role of Dmrt-1 in the differentiation process.

PMID- 16630120
TI  - Cervical and corpus cancer survival disparities by socioeconomic status in a
      metropolitan area of Japan.
AB  - The purpose of this study was to analyze socioeconomic differences in cervical
      and corpus cancer survival, and to investigate if the differences are due to
      differences in age, cancer stage, histology and treatment. A total of 14,055
      cases with cervical cancer and 3,113 cases with corpus cancer were obtained from
      the Osaka Cancer Registry. Municipality-based SES measurements were obtained from
      the System of Social and Demographic Statistics. Survival analysis was carried
      out with Kaplan-Meier survival curves. Three types of Cox proportional hazards
      regression models were tested to assess survival differences among groups and
      effects of SES on survival, controlling for clinical factors. SES was related to
      age and cancer stage for cervical and corpus cancer patients, and histology for
      cervical cancer patients. Differences were observed in cumulative 5-year survival
      for cervical cancer patients among low, middle and high unemployment
      municipalities (68.9%, 64.3% and 50.9%, respectively, P<0.0001). Differences in
      cumulative 5-year survival for cervical cancer patients were also observed among
      high, middle and low education municipalities (65.1%, 62.2% and 56.1%,
      respectively, P<0.0001). Similar patterns in 5-year survival were also found for
      corpus cancer patients. After adjusting for age, cancer stage, histology and
      treatment, survival differences between patients from high and low SES areas
      still remained. In conclusion, our population-based analysis of a metropolitan
      representative sample in Japan has demonstrated, for the first time in Japan, SES
      differences in survival following cervical and corpus cancer.

PMID- 16630121
TI  - Infrequent existence of simian virus 40 large T antigen DNA in malignant
      mesothelioma in Japan.
AB  - Malignant mesothelioma is the most common primary pleural neoplasm. Association
      of simian virus 40 (SV40) with malignant mesothelioma has been reported,
      suggesting that SV40 plays an important role in the origin of a subset of these
      tumors. However, significant geographic variation is present as to how often this
      association occurs. As no study concerning SV40 in malignant mesothelioma has
      been reported from Japan, we examined the frequency of SV40 infection in Japanese
      malignant mesothelioma cases. In pleural malignant mesothelioma tissue from 35
      patients in Japan, we sought the presence of SV40 large T antigen DNA using real
      time polymerase chain reaction (PCR), as well as expression of the viral protein
      using immunohistological methods. Real-time PCR demonstrated that two of 35
      mesotheliomas contained DNA sequences encoding portions of SV40 large T antigen.
      None of the 35 malignant mesothelioma specimens showed immunoreactivity for SV40
      large T antigen. SV40 infection does not appear to have a major role in the
      development of malignant mesothelioma in Japan.

PMID- 16630122
TI  - Shock wave induced cytoskeletal and morphological deformations in a human renal
      carcinoma cell line.
AB  - Effects of shock waves on the morphology and cytoskeleton of a human renal
      carcinoma cell line (ACHN) were investigated in vitro. ACHN monolayer cultured on
      a cover slide glass was treated with 10 shots of focused underwater shock waves,
      with 16 MPa peak pressure at the focal area of a piezoceramic shock wave
      generator. After exposure to the shock wave, based on the severity of
      morphological deformations of the treated cells, the monolayer was divided into
      three morphological areas; focal, marginal and intact. Morphological deformations
      were found to be associated with disorganization of the intracellular
      cytoskeletal filaments. Deformation of the cytoskeletal proteins in the treated
      cells were separately studied with respect to the location of the cells within
      the three morphological areas. Among three major cytoskeletal proteins, actin and
      tubulin, but not vimentin, were affected by the shock waves. The deformed cells
      reorganized their cytoskeletal network within 3 h with a pattern similar to the
      control, indicating the transient characteristic of the shock wave induced
      cytoskeletal damage in the surviving cells. The remaining cell fragments on the
      slide glass, which contained short actin filaments, indicated the important role
      of shear stress in damaging the cytoskeletal fibers by shock waves.

PMID- 16630123
TI  - Randomized phase II study of concurrent and sequential rituximab and CHOP
      chemotherapy in untreated indolent B-cell lymphoma.
AB  - CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective
      treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal
      combination schedule remains unknown. We performed a randomized phase II study to
      explore a more promising schedule in untreated, advanced indolent B-NHL. Patients
      were randomized to receive either six courses of CHOP concurrently with rituximab
      (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm
      S). A total of 69 patients received the concurrent (n=34) or sequential (n=35)
      regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval
      [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95%
      CI, 85-100), including a 68% CR in Arm S. Patients in Arm C experienced more
      grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non
      hematological toxicities (21%versus 12%). Both arms were tolerated well. With a
      median follow-up of 28.2 months, the median progression-free survival (PFS) time
      was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly
      effective in untreated indolent B-NHL, either concurrent or in a sequential
      combination. Both combination schedules deserve further investigation.

PMID- 16630124
TI  - Cationized gelatin delivery of a plasmid DNA expressing small interference RNA
      for VEGF inhibits murine squamous cell carcinoma.
AB  - Double-stranded RNA (dsRNA) plays a major role in RNA interference (RNAi), a
      process in which segments of dsRNA are initially cleaved by the Dicer into
      shorter segments (21-23 nt) called small interfering RNA (siRNA). These siRNA
      then specifically target homologous mRNA molecules causing them to be degraded by
      cellular ribonucleases. RNAi down regulates endogenous gene expression in
      mammalian cells. Vascular endothelial growth factor (VEGF) is a key molecule in
      vasculogenesis as well as in angiogenesis. Tumor growth is an angiogenesis
      dependent process, and therapeutic strategies aimed at inhibiting angiogenesis
      are theoretically attractive. To investigate the feasibility of using siRNA for
      VEGF in the specific knockdown of VEGF mRNA, thereby inhibiting angiogenesis, we
      have performed experiments with a DNA vector based on a siRNA system that targets
      VEGF (siVEGF). It almost completely inhibited the expression of three different
      isoforms (VEGF120, VEGF164 and VEGF188) of VEGF mRNA and the secretion of VEGF
      protein in mouse squamous cell carcinoma NRS-1 cells. The siVEGF released from
      cationized gelatin microspheres suppressed tumor growth in vivo. A marked
      reduction in vascularity accompanied the inhibition of a siVEGF-transfected
      tumor. Fluorescent microscopic study showed that the complex of siVEGF with
      cationized gelatin microspheres was still present around the tumor 10 days after
      injection, while free siVEGF had vanished by that time. siVEGF gene therapy
      increased the fraction of vessels covered by pericytes and induced expression of
      angiopoietin-1 by pericytes. These data suggest that cationized-gelatin
      microspheres containing siVEGF can be used to normalize tumor vasculature and
      inhibit tumor growth in a NRS-1 squamous cell carcinoma xenograft model.

PMID- 16630125
TI  - Curcumin targets Akt cell survival signaling pathway in HTLV-I-infected T-cell
      lines.
AB  - The Akt signaling pathway is important for survival and growth of cancer cells.
      In the present paper we show that the Akt signaling pathway is constitutively
      activated in human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines
      and in primary adult T-cell leukemia (ATL) cells. Curcumin, a natural compound
      present in turmeric, has been studied vigorously as a potent chemopreventive
      agent for cancer therapy because of its inhibitory effect on proliferation and
      induction of apoptosis in several tumor cell lines. We investigated the effect of
      curcumin on Akt activity in HTLV-I-infected T-cell lines and primary ATL cells.
      Phosphorylated PDK1 is an activator of Akt by phosphorylating Akt. Curcumin
      reduced phosphorylation of PDK1 and inhibited constitutive activation of Akt.
      Curcumin activated glycogen synthase kinase (GSK)-3beta, a downstream target of
      Akt kinase, by inhibiting phosphorylation of this protein. Curcumin reduced the
      expression of cell cycle regulators, cyclin D1 and c-Myc proteins, which are both
      degraded by activated GSK-3beta. Our results suggest that activation of the Akt
      signaling pathway plays an important role in ATL cell survival, and that curcumin
      may have anti-ATL properties mediated, at least in part, by inhibiting Akt
      activity. We propose that Akt-targeting agents could be useful for the treatment
      of ATL. In this regard, curcumin is a potentially promising compound for the
      treatment of ATL.

PMID- 16630126
TI  - Current progress of cancer chemotherapy The Fifteenth International Symposium of
      the Hiroshima Cancer Seminar, October 2005.

PMID- 16630127
TI  - Tenth Japanese-German Workshop on Molecular and Cellular Aspects of
      Carcinogenesis, Essen, Germany, 29 September-1 October 2005.

PMID- 16630129
TI  - Heparin-binding epidermal growth factor-like growth factor as a novel targeting
      molecule for cancer therapy.
AB  - HB-EGF, a member of the EGF family of growth factors, exerts its biological
      activity through activation of the EGFR and other ErbB receptors. HB-EGF
      participates in diverse biological processes, including heart development and
      maintenance, skin wound healing, eyelid formation, blastocyst implantation,
      progression of atherosclerosis and tumor formation, through the activation of
      signaling molecules downstream of ErbB receptors and interactions with molecules
      associated with HB-EGF. Recent studies have indicated that HB-EGF gene expression
      is significantly elevated in many human cancers and its expression level in a
      number of cancer-derived cell lines is much higher than those of other EGFR
      ligands. Several lines of evidence have indicated that HB-EGF plays a key role in
      the acquisition of malignant phenotypes, such as tumorigenicity, invasion,
      metastasis and resistance to chemotherapy. Studies in vitro and in vivo have
      indicated that HB-EGF expression is essential for tumor formation of cancer
      derived cell lines. CRM197, a specific inhibitor of HB-EGF, and an antibody
      against HB-EGF are both able to inhibit tumor growth in nude mice. These results
      indicate that HB-EGF is a promising target for cancer therapy, and that the
      development of targeting tools against HB-EGF could represent a novel type of
      therapeutic strategy, as an alternative to targeting ErbB receptors.

PMID- 16630130
TI  - Non-viral vectors for cancer therapy.
AB  - Cancers are diverse and often resistant to therapeutic strategies. Gene therapy
      has yet to meet the promise of a breakthrough in cancer therapy. There are
      several barriers to overcome in cancer gene therapy. One of the biggest
      challenges is the design of appropriate vectors. Numerous viral and non-viral
      methods for gene transfer have been developed for human gene therapy, but both
      viral and non-viral vectors have limitations and advantages. In this review
      article, recent improvements in the development of non-viral vectors for
      delivering gene therapy for the treatment of cancer will be discussed.

PMID- 16630131
TI  - Mouse models of gastrointestinal tumors.
AB  - The laboratory mouse (Mus musculus) has become one of the best model animal
      species in biomedical research today because of its abundant genetic/genomic
      information, and easy mutagenesis using transgenic and gene knockout technology.
      Genetically engineered mice have become essential tools in both mechanistic
      studies and drug development. In this article I will review recent topics in
      gastrointestinal cancer model mice, with emphasis on the results obtained in our
      laboratory. They include: (i) mouse models for familial adenomatous polyposis
      (Apc mutant mice; modifier genes of Apc intestinal polyposis; stabilizing beta
      catenin mutant mice); (ii) mouse models for colon cancer (mouse models for
      hereditary non-polyposis colon cancer; additional mutations in Apc mutant mice;
      models with mutations in other genes; models for colon cancer associated with
      inflammatory bowel diseases); and (iii) mouse models for gastric cancer.

PMID- 16630132
TI  - Significant increase of colonic mutated crypts correlates with age in sporadic
      cancer and diverticulosis cases, with higher frequency in the left- than right
      side colorectum.
AB  - Mild periodic acid-Schiff (mPAS) staining can discriminate non-O-acetylated (mPAS
      positive) from O-acetylated (mPAS-negative) epithelial sialoglycoproteins in
      human colonic mucosa, allowing the three haplotypes expressed from a single
      polymorphic autosomal gene (oat) to be distinguished. In heterozygotes, we
      previously demonstrated wholly mPAS-positive (stem cell mutated) crypts and
      clusters of two or more mPAS-positive crypts to be significantly increased with
      duration of ulcerative colitis. To establish whether such an increase in the
      number of mutated crypts with age also occurs in normal individuals or in cases
      with diverticulosis, the O-acetylation phenotype in the non-cancerous colonic
      mucosa of 47 sporadic colorectal cancer patients who were heterozygotes for oat
      was tested with mild-PAS staining. PAS-positive crypts were assessed
      histologically in relation to age and compared between the left (sigmoid colon
      and rectum) and right (cecum and ascending colon) sides of the colorectum. Wholly
      mPAS-positive (stem cell mutated) crypts and foci in heterozygotes were found to
      be increased significantly (P < 0.0001) in the left side with aging (r = 0.598
      and 0.643, respectively). Such a positive correlation with aging was also
      confirmed in 19 diverticulosis cases without cancer (r = 0.797 and 0.793,
      respectively). The frequency of mutated crypts and foci on the right side was
      significantly lower than on the left side in both spontaneous colorectal cancer
      and diverticulosis cases. The results provide support for an intimate
      relationship between accumulation of mutated crypts with aging, possibly with
      significance for colorectal cancer development. Furthermore, the environment in
      the right side of the colon may be different from that in the left side in this
      regard.

PMID- 16630133
TI  - Lung as a new target in rats of 2-amino-3-methylimidazo[4,5-f]quinoline
      carcinogenesis: results of a two-stage model initiated with N-bis(2
      hydroxypropyl)nitrosamine.
AB  - The effects of IQ on the promotion stage of DHPN-induced lung carcinogenesis and
      contributions of oxidative stress were investigated in rats. Groups of 20 male 6
      week-old F344 rats were given 0.1% DHPN in their drinking water for 2 weeks for
      initiation. From the age of 9 weeks, they were treated with 0, 150 and 300 p.p.m.
      of IQ in the diet for 27 weeks. Control rats were similarly fed 300 p.p.m. IQ or
      basal diet alone without the preceding initiation. IQ clearly (P < 0.01) enhanced
      the multiplicity of lung tumors in a dose-dependent manner (DHPN alone, 3.63 +/-
      1.80; DHPN +150 p.p.m. IQ, 11.50 +/- 5.04; DHPN +300 p.p.m. IQ, 18.83 +/- 4.58
      [no./rat]). In addition, the incidence of lung tumors in the 300 p.p.m. IQ alone
      group (25%) was significantly (P < 0.05) higher than that in the non-treatment
      group (0%). In a second experiment, male rats were given IQ at doses of 0 and 300
      p.p.m. in the diet for one week in order to analyze 8-OHdG formation, levels of
      TBARS and BrdU-LI in the lungs. There were no changes in 8-OHdG or TBARS levels,
      but significant elevation of BrdU-LI occurred in the IQ administration group. The
      overall data clearly indicate that IQ is a potent lung carcinogen in rats, in
      which oxidative stress may not be involved in lung carcinogenesis.

PMID- 16630134
TI  - MTA1 overexpression correlates significantly with tumor grade and angiogenesis in
      human breast cancers.
AB  - Metastasis associated antigen 1 (MTA1) is a recently identified candidate
      metastasis-associated gene that plays an important role in tumorigenesis and
      tumor aggressiveness, especially tumor invasiveness and metastasis. We analyzed
      the relationship between MTA1 expression and variable clinicopathological
      features and characterized its role in tumor angiogenesis in human breast
      cancers. Two hundred and sixty-three breast cancer cases that successfully
      underwent surgery at Hanyang University Hospital (Seoul, Korea) between January
      1989 and December 1997 were enrolled. MTA1 expression was observed by
      immunohistochemical staining and correlated with intratumoral microvessel density
      (MVD) and other clinicopathological parameters. MTA1 overexpression correlated
      significantly with higher tumor grade (grades 1 and 2 vs grade 3, P = 0.009).
      However, MTA1 expression did not correlate with tumor stage, status of estrogen
      and progesterone receptors, or axillary lymph node metastasis. Interestingly,
      MTA1 expression was found to correlate significantly with tumor MVD (P = 0.002).
      Survival analysis did not show a significant difference between MTA1
      overexpression and poorer survival. In conclusion, MTA1 overexpression was found
      to be closely associated with higher tumor grade and increased tumor
      angiogenesis. These findings suggest MTA1 as a predictor of aggressive phenotype
      and a possible target molecule for anti-angiogenic drugs in breast cancer
      treatment.

PMID- 16630135
TI  - Presence of serum tripartite motif-containing 21 antibodies in patients with
      esophageal squamous cell carcinoma.
AB  - SEREX has been applied to esophageal SCC, and the TRIM21 gene was identified as a
      novel SEREX antigen of esophageal SCC. The presence of s-TRIM21-Abs was confirmed
      by Western blotting using bacterially expressed TRIM21 gene product and was
      evaluated for clinicopathological significance in patients with esophageal SCC. s
      TRIM21-Abs were detected in 18 (20%) of 91 patients with esophageal SCC but not
      in 42 healthy donors. The presence of s-TRIM21-Abs was partly associated with
      tumor size (P = 0.063) and poor survival (P = 0.067). To measure serum antibody
      levels, ELISA using purified recombinant TRIM21 protein was developed. The levels
      of s-TRIM21-Abs were significantly higher in patients with esophageal SCC than in
      healthy donors (P = 0.013). s-TRIM21-Abs may be a useful tumor marker to diagnose
      and predict disease progression in patients with esophageal SCC.

PMID- 16630136
TI  - Establishment and characterization of four malignant pleural mesothelioma cell
      lines from Japanese patients.
AB  - Malignant pleural mesothelioma (MPM) is an asbestos-related malignancy that is
      highly resistant to current therapeutic modalities. We established four MPM cell
      lines (ACC-MESO-1, ACC-MESO-4, Y-MESO-8A and Y-MESO-8D) from Japanese patients,
      with the latter two from the same patient with biphasic-like characteristics of
      MPM, showing epithelial and sarcomatous phenotypes, respectively, in cell
      culture. These cells grew well in RPMI-1640 medium supplemented with 10% fetal
      bovine serum under 5% CO2. Mutation and expression analyses demonstrated that the
      tumor suppressor gene NF2, which is known to be one of the most frequently
      mutated in MPM, is mutated in ACC-MESO-1. We detected homozygous deletion of
      p16INK4A/p14ARF in all four MPM cell lines. However, mutations of other tumor
      suppressor genes, including TP53, and protooncogenes, including KRAS, NRAS, BRAF,
      EGFR and HER2, were not found in these cell lines. Polymerase chain reaction
      amplification of the simian virus 40 sequence did not detect any products. We
      also analyzed genetic alterations of six other MPM cell lines and confirmed
      frequent mutations of NF2 and p16INK4A/p14ARF. To characterize the biological
      differences between Y-MESO-8A and Y-MESO-8D, we carried out cDNA microarray
      analysis and detected genes that were differentially expressed in these two cell
      lines. Thus, our new MPM cell lines seem to be useful as new models for studying
      various aspects of the biology of human MPM as well as materials for the
      development of future therapies.

PMID- 16630137
TI  - Plasminogen activator inhibitor-1 as a potential marker for the malignancy of
      gastric cancer.
AB  - To test the hypothesis that plasminogen activator inhibitor-1 (PAI-1) may serve
      as a candidate marker for the malignancy of gastric cancer, we carried out
      quantitative reverse transcription-polymerase chain reaction for the PAI-1 gene
      and evaluated the possible relationship between PAI-1 gene expression levels and
      clinicopathological findings in gastric cancer. A significant increase in PAI-1
      expression scores was observed in lymph node metastasis-positive gastric cancers
      (2.11 +/- 0.35) compared to metastasis-negative cancers (0.33 +/- 0.49) (P =
      0.0048), as well as in distant metastasis-positive gastric cancers (3.68 +/-
      0.58) compared to metastasis-negative cancers (1.20 +/- 0.32). The PAI-1
      expression score markedly increased with tumor stage (P < 0.0001; ANOVA test).
      Moreover, multivariate analysis revealed the PAI-1 expression score to be a
      strong and independent prognostic factor for gastric cancer (P = 0.0450). These
      results suggested that PAI-1 might serve as a new and promising parameter for the
      prediction of prognosis in gastric cancer.

PMID- 16630138
TI  - Detection of germline deletions using real-time quantitative polymerase chain
      reaction in Japanese patients with von Hippel-Lindau disease.
AB  - Germline mutations of the VHL gene are responsible for VHL. Approximately 70% of
      VHL families display small intragenic mutations detectable by sequencing, whereas
      partial- or whole-gene deletions have been described in the majority of the
      remaining families. For such large deletions, complex genetic techniques other
      than sequencing might have to be used. In this study, we describe an RQ-PCR assay
      with TaqMan fluorescent probes to detect germline VHL deletions. The RQ-PCR
      primer/probe sets were designed for the three VHL coding exons as well as for the
      5' promoter and 3' untranslated regions. The RQ-PCR assay for 30 normal and 10
      known VHL deletion control samples demonstrated high sensitivity and specificity.
      We then screened 29 individuals from 19 classical VHL families (16 type 1, 2 type
      2A, and one type 2B) and one PHEO family, as well as four solitary suspected
      cases, none displaying any sequence changes, for VHL deletions by the RQ-PCR
      assay. We detected germline deletions in 17 (89%) classical families including 15
      type 1, one type 2A, and one type 2B. We also identified two mutation carriers
      and two non-carriers in our family cohort. The one PHEO family and four solitary
      cases did not display any deletion patterns. These findings indicated that the
      TaqMan-based RQ-PCR assay is a simple and potent technique for the rapid,
      sensitive, and specific investigation of VHL genetic diagnoses that could be used
      profitably before more complex large-deletion detection techniques.

PMID- 16630139
TI  - Genetic polymorphism of cholesterol 7alpha-hydroxylase (CYP7A1) and colorectal
      adenomas: Self Defense Forces Health Study.
AB  - Bile acids have long been implicated in colorectal carcinogenesis, but
      epidemiological evidence is limited. Cholesterol 7alpha-hydroxylase (CYP7A1) is
      the rate-limiting enzyme producing bile acids from cholesterol. A recent case
      control study showed a decreased risk of proximal colon cancer associated with
      the CC genotype of the CYP7A1 A-203C polymorphism. The present study examined the
      relationship between the CYP7A1 A-203C polymorphism and colorectal adenoma, which
      is a well-established precursor lesion of colorectal cancer. The study subjects
      comprised 446 cases of colorectal adenomas and 914 controls of normal total
      colonoscopy among men receiving a preretirement health examination at two
      hospitals of the Self Defense Forces (SDF). The CYP7A1 genotype was determined by
      the polymerase chain reaction-restriction fragment length polymorphism method.
      Statistical adjustment was made for age, hospital, rank in the SDF, smoking,
      alcohol use, body mass index, physical activity and parental history of
      colorectal cancer. The CYP7A1 polymorphism was not measurably related to the
      overall risk of colorectal adenomas. However, the CC genotype was associated with
      a decreased risk of proximal colon adenomas, but not of distal colon and rectal
      adenomas. Adjusted odds ratios of proximal colon adenomas (95% confidence
      intervals) for the AC and CC genotype versus AA genotype were 0.82 (0.54-1.24)
      and 0.56 (0.34-0.95), respectively. The findings add to evidence for the role of
      bile acids in colorectal carcinogenesis. The CC genotype of the CYP7A1 A-203C
      polymorphism probably renders lower activity of the enzyme synthesizing bile
      acids.

PMID- 16630140
TI  - Identification of secernin 1 as a novel immunotherapy target for gastric cancer
      using the expression profiles of cDNA microarray.
AB  - Despite the discovery of multiple TAAs, only a limited number is available for
      clinical application, particularly against epithelial malignancies. In this study
      we searched for novel TAAs using expression profiles of gastric cancer examined
      with cDNA microarray, and identified the SCRN1 gene as a candidate. SCRN1 was
      confirmed to be expressed in five out of seven gastric cancers with
      semiquantitative RT-PCR. With Northern blot analysis, it was detected abundantly
      in the testis and ovary, but it was barely detectable in 14 other normal human
      adult organs. Colony formation assay revealed that its augmented expression is
      associated with promoted cell growth. As these expression profiles and functional
      features of SCRN1 appeared to be compatible with the characteristics of the
      hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic
      epitope peptides restricted to HLA-A*0201. We synthesized the candidate peptides
      derived from SCRN1, and tried to induce CTLs with each peptide. The CTL clones
      were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed
      not only the peptide-pulsed targets but also the tumor cells expressing both
      SCRN1 and HLA-A*0201 endogenously. These results strongly suggest that SCRN1-196
      is an epitope peptide restricted to HLA-A*0201. Furthermore, we synthesized an
      anchor-modified peptide SCRN1-9 V (KMDAEHPEV), in which leucine at position 9 was
      substituted for valine to increase the binding affinity to the HLA-A*0201
      molecules. The CTL clones induced by SCRN1-9 V also recognized tumor cells
      expressing its natural SCRN1 protein endogenously. These results strongly suggest
      that SCRN1 is a novel TAA and these peptides, both native and modified, may be
      applicable for cancer vaccines to treat gastric cancer.

PMID- 16630141
TI  - Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of
      surface molecules by MUC1 capping.
AB  - Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein
      that is frequently overexpressed on the surface of many human adenocarcinomas.
      Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor-associated
      antigen that has been intensely studied as a target for cancer immunotherapy. We
      previously identified a mouse IgG(1) mAb that recognizes a sialylated sugar
      chain, designated as KL-6, classified in 'Cluster 9 (MUC1)'. Using the anti-KL-6
      mAb, we investigated antitumor effects of anti-MUC1 mAb on breast cancer cell
      lines expressing MUC1 abundantly. We showed that anti-KL-6 mAb induced capping of
      MUC1 and facilitated E-cadherin-mediated cell-cell interaction in the breast
      cancer cell lines YMB-S and ZR-75-1S, which proliferate in suspension culture
      without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of
      lymphokine-activated killer cells. These results indicate that the capping of
      MUC1 restores cell surface proteins, such as adhesion molecules and tumor
      antigens, to work in cell-cell interactions, leading to inhibition of tumor
      proliferation due to cell-cell adhesion and increased accessibility to effector
      cells that are needed to kill tumor cells.

PMID- 16630142
TI  - Cell cycle arrest and apoptotic induction in LNCaP cells by MCS-C2, novel cyclin
      dependent kinase inhibitor, through p53/p21WAF1/CIP1 pathway.
AB  - The purpose of the present study was to investigate the mechanisms involved in
      the antiproliferative and apoptotic effects of MCS-C2, a novel analog of the
      pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human
      prostate cancer LNCaP cells. MCS-C2, a selective inhibitor of cyclin-dependent
      kinase, was found to inhibit cell growth in a time- and dose-dependent manner,
      and inhibit cell cycle progression by inducing the arrest of the G1 phase and
      apoptosis in LNCaP cells. When treated with 3 microM MCS-C2, inhibited
      proliferation associated with apoptotic induction was found in the LNCaP cells in
      a concentration and time-dependent manner, and nuclear DAPI staining revealed the
      typical nuclear features of apoptosis. Furthermore, MCS-C2 induced cell cycle
      arrest in the G1 phase through the upregulated phosphorylation of the p53 protein
      at Ser-15 and activation of its downstream target gene p21WAF1/CIP1. Accordingly,
      these results suggest that MCS-C2 inhibits the proliferation of LNCaP cells by
      way of G1-phase arrest and apoptosis in association with the regulation of
      multiple molecules in the cell cycle progression.

PMID- 16630144
TI  - Platelet activation in asthma: integral to the inflammatory response.

PMID- 16630146
TI  - Platelet activation in allergic asthma patients during allergen challenge with
      Dermatophagoides pteronyssinus.
AB  - BACKGROUND: Animal models of allergic asthma indicate that intravascular platelet
      activation is necessary for the development of allergen-induced chronic airway
      inflammation. OBJECTIVE: To evaluate whether the development of a late asthmatic
      response (LAR) in allergic asthma patients challenged with a relevant allergen is
      consequent to platelet activation. METHODS: Thirty-three house dust mite
      sensitive asthmatic patients were challenged intrabronchially with
      Dermatophagoides pteronyssinus (Dp) extract. Twelve non-atopic healthy subjects
      (HC) were used as controls. Platelet count and plasma levels of beta
      thromboglobulin (beta-TG), platelet factor-4 (PF-4) and soluble P-selectin (sP
      selectin) were assessed before the challenge (T(0)) and 30 min (T(EAR)), 6 h
      (T(LAR)) and 24 h (T(24)) after the challenge. RESULTS: Eleven patients responded
      to allergen challenge with an isolated early asthmatic response (single
      responders, SR). In 22 patients dual asthmatic response was demonstrated (dual
      responders, DR). At T(0) neither the platelet count nor the mean plasma level of
      beta-TG in DR or SR were different from HC, the mean plasma level of PF-4 in SR
      was significantly greater than in HC (P=0.01) or DR (P=0.001), the mean plasma
      level of sP-selectin was significantly greater in DR than in HC (0.0002) but not
      statistically different from SR (P=0.055). A significant decrease in the platelet
      count and increase in the plasma level of all the studied markers was seen at
      T(EAR), which was followed by a gradual return to the baseline values in the SR.
      Elevated plasma levels of platelet activation markers and decreased platelet
      count were seen in the DR even at T(24). Strong correlation was found between the
      increase in plasma concentration of beta-TG at T(EAR) and the maximum fall in
      forced expiratory volume in 1 s at T(LAR) (r=-0.57; P=0.0006). CONCLUSION: In
      allergic asthma patients development of prolonged airway inflammation after
      allergen challenge is associated with intravascular platelet activation.

PMID- 16630145
TI  - Too clean, or not too clean: the hygiene hypothesis and home hygiene.
AB  - The 'hygiene hypothesis' as originally formulated by Strachan, proposes that a
      cause of the recent rapid rise in atopic disorders could be a lower incidence of
      infection in early childhood, transmitted by unhygienic contact with older
      siblings. Use of the term 'hygiene hypothesis' has led to several
      interpretations, some of which are not supported by a broader survey of the
      evidence. The increase in allergic disorders does not correlate with the decrease
      in infection with pathogenic organisms, nor can it be explained by changes in
      domestic hygiene. A consensus is beginning to develop round the view that more
      fundamental changes in lifestyle have led to decreased exposure to certain
      microbial or other species, such as helminths, that are important for the
      development of immunoregulatory mechanisms. Although this review concludes that
      the relationship of the hypothesis to hygiene practice is not proven, it lends
      strong support to initiatives seeking to improve hygiene practice. It would
      however be helpful if the hypothesis were renamed, e.g. as the 'microbial
      exposure' hypothesis, or 'microbial deprivation' hypothesis, as proposed for
      instance by Bjorksten. Avoiding the term 'hygiene' would help focus attention on
      determining the true impact of microbes on atopic diseases, while minimizing
      risks of discouraging good hygiene practice.

PMID- 16630147
TI  - Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin
      intolerant asthma in males.
AB  - BACKGROUND: Cysteinyl leukotrienes (CysLTs) play important roles in the
      pathogenesis of eosinophilic airway inflammation characterized by
      bronchoconstriction, mucus secretion and airway hyper-responsiveness via
      cysteinyl leukotriene receptor 1 (CysLTR1)-mediated mechanism. CysLTR1-selective
      antagonists have anti-bronchoconstrictive and anti-inflammatory effects in
      asthma, particularly aspirin-intolerant asthma (AIA). METHODS: To investigate the
      association of CysLTR1 with AIA development, we identified three single
      nucleotide polymorphisms (SNPs), -634C>T, -475A>C, -336A>G, in the 5' upstream
      region of CysLTR1 gene using a direct sequencing method in 105 AIA patients, 110
      ASA-tolerant asthma (ATA) patients and 125 normal healthy controls (NC). RESULTS:
      Significant differences were observed in allele frequencies of the three SNPs
      within male subjects; Male AIA patients had higher frequencies of the minor
      alleles of these three SNPs than male control groups (P=0.03 for AIA vs. NC;
      P=0.02 for AIA vs. ATA). Moreover, three-SNP haplotype, ht2 [T-C-G], was
      associated with increased disease risk (odds ratio (OR)=2.71, P=0.03 for AIA vs.
      NC; OR=2.89, P=0.02 for AIA vs. ATA) in males. CysLTR1 haplotypes were also
      associated with altered gene expression; luciferase activity was significantly
      enhanced with the ht2 [T-C-G] construct in comparison with the ht1 [C-A-A]
      construct in human Jurkat cells (P=0.04). CONCLUSION: These results suggest that
      genetic variants of CysLTR1 are associated with AIA in a Korean population, and
      may modulate CysLTR1 expression.

PMID- 16630148
TI  - Polymorphisms in manganese superoxide dismutase and catalase genes: functional
      study in Hong Kong Chinese asthma patients.
AB  - BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma.
      Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase
      (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To
      investigate the association of the manganese-containing form of SOD (MnSOD) gene
      at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T
      and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS:
      The association study was conducted in a case-control design in asthma patients
      (n=251) and healthy controls (n=316) by genotyping. The functional significance
      was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The
      Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were
      not different between patients and controls, while the C allele of catalase gene
      at C-262T was found to be significantly different between patients and controls
      (P=0.033). The less frequent variant of catalase gene (-262T) was found to be
      protective from the development of asthma in a Hong Kong Chinese non-smoking
      population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had
      elevated erythrocyte SOD and catalase activities in comparison with healthy
      controls (P<0.01). However, their activities were not associated with different
      genotypes within healthy controls or asthma patients. CONCLUSION: This is the
      first report showing that SOD and catalase functional activities are not
      associated with their respective genetic polymorphisms but related to the
      presence of asthma in a Hong Kong Chinese population.

PMID- 16630149
TI  - Mucin genes have different expression patterns in healthy and diseased upper
      airway mucosa.
AB  - BACKGROUND: Mucus hyper-secretion is a feature of several airways diseases such
      as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are
      major components of mucus, the knowledge of their distribution and regulation in
      nasal tissues is likely to improve mucus hyper-secretion therapy. OBJECTIVE: The
      aim of this study was to evaluate and compare mucin gene expression at epithelial
      and glandular levels, and to identify potential mucin expression patterns for
      specific upper airways pathologies. METHODS: Immunohistochemistry for MUC1, MUC2,
      and MUC4-MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral
      nasal polyps (NP; n=38), NP from CF patients (n=10), and antrochoanal (AC) polyps
      (n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in
      situ hybridization. RESULTS: MUC1, MUC4, and MUC5AC mucins were highly expressed
      in the epithelium and their expression pattern was similar in all NP types, MUC1
      and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly
      detected at both epithelial and glandular levels with marked variability between
      groups. MUC5B was mainly detected in glands and the expression in all polyp types
      was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from
      CF patients than in bilateral NP and healthy NM. Although MUC2 expression was
      low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and
      MUC7 were scarcely detected and MUC7 expression was restricted to glands.
      CONCLUSIONS: These results suggest that NP have a different pattern of mucin
      expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps
      (decreased MUC2) have a different mucin expression pattern than bilateral NP.

PMID- 16630150
TI  - Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal
      allergic responses.
AB  - BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released
      during mast cell degranulation and tryptase/trypsin inhibitors are a novel
      potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES:
      This study was performed to assess the effects of RWJ-58643 on nasal symptoms,
      eosinophil influx, and cytokine and chemokine release following nasal allergen
      challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis
      (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or
      matched placebo given 30 min before NAC in a double-blind, randomized crossover
      design. A single dose of 200 microg budesonide was studied in an open-label
      extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal
      device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5
      (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug
      administration. Nasal lavage mediators were analysed using a sensitive
      multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and
      budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of
      IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg)
      caused a late eosinophilia and preceding increases in IL-5 compared with placebo.
      CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin
      inhibition has therapeutic potential in allergic inflammation, however, this
      property is dose responsive and higher doses are ineffective and may cause
      eosinophilia.

PMID- 16630151
TI  - Induction of interleukin-10 and suppressor of cytokine signalling-3 gene
      expression following peptide immunotherapy.
AB  - BACKGROUND: Allergen-derived (T cell epitope) peptides may be safer for
      immunotherapy than native allergen, as they do not cross-link immunoglobulin
      (Ig)E. However, HLA polymorphism results in multiple potential epitopes.
      Synthetic peptides of phospholipase (PL) A(2) were selected for a peptide
      vaccine, on the basis of binding affinity for commonly expressed HLA-DR
      molecules. OBJECTIVE: To evaluate treatment with an HLA-DR-based PLA(2) peptide
      vaccine in subjects with mild honeybee allergy in an open, controlled study.
      METHODS: Twelve volunteers with allergy to bee venom received nine intradermal
      injections of PLA(2) peptides, with six untreated subjects serving as controls.
      Outcome was assessed by the size of the late-phase cutaneous reaction to
      allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine
      release, and expression of genes associated with immune regulation. RESULTS:
      Subjects receiving peptides showed a decrease in the magnitude of the late-phase
      cutaneous reaction to bee venom compared with controls (P=0.03). The
      proliferation of venom-stimulated PBMCs decreased in treated subjects compared
      with controls (P=0.01). Peptide treatment reduced the production of IL-13 by
      PLA(2)-stimulated PBMCs (P<0.01) and IFN-gamma (P<0.01), and increased the
      production of IL-10 (P=0.02). Transcription of the suppressor of cytokine
      signalling (Socs)3 gene was significantly increased following therapy. A
      transient, but modest, increase in allergen-specific IgG was also observed.
      CONCLUSION: HLA-DR-based T cell epitopes modify surrogate markers associated with
      successful immunotherapy and induction of immune regulation, supporting the
      concept that this form of treatment may be efficacious in human allergic disease.

PMID- 16630152
TI  - Inhibitory effects of fluvastatin on cytokine and chemokine production by
      peripheral blood mononuclear cells in patients with allergic asthma.
AB  - BACKGROUND: Statins have anti-inflammatory effects on immune cells. OBJECTIVE: To
      investigate the immunomodulatory effects of fluvastatin on peripheral blood
      mononuclear cells (PBMCs) after allergen-specific and non-allergen-specific
      stimulation in patients with asthma and in healthy subjects. METHODS: PBMCs from
      seven patients with asthma who showed elevated immunoglobulin (Ig)E to house dust
      mite were isolated and stimulated with Dermatofagoides farinae, purified protein
      derivative, and phytohaemagglutinin (PHA) in the presence or absence of
      fluvastatin. PBMCs from seven healthy subjects were stimulated with PHA. The
      effects of fluvastatin on cell proliferation and production of cytokines
      (interferon [IFN]-gamma and interleukin [IL]-5) and chemokines (chemokine CXC
      motif, ligand [CXCL10], and CC chemokine ligand [CCL17]) were measured. Migration
      of T helper (Th)1 and Th2 cell lines was also investigated. The expression of
      CXCR3 and CCR4 was analysed with flow cytometry. Steroid-insensitive PBMCs
      induced by preculture with IL-2 and IL-4 were also evaluated. Some experiments
      were performed in the presence of mevalonic acid. RESULTS: Fluvastatin inhibited
      the proliferation of PBMCs and decreased the production of IL-5, IFN-gamma,
      CCL17, and CXCL10 after allergen-specific and non-allergen-specific stimulation;
      all these effects, except for decreased CXCL10 production, were partially
      reversed by mevalonic acid. Culture supernatants obtained in the presence of
      fluvastatin prevented the migration of Th1 and Th2 cell lines in a dose-dependent
      manner. In addition, CCR4 and CXCR3 expression on CD4(+) T cells was not affected
      by the presence of fluvastatin. Fluvastatin inhibited the proliferative response
      of steroid-insensitive PBMCs to phytohaemagglutinin. CONCLUSION: Fluvastatin has
      inhibitory effects on cytokine and chemokine production, and thus might be used
      as a potential therapeutic agent in severe asthma.

PMID- 16630153
TI  - The prognosis of occupational asthma due to detergent enzymes: clinical,
      immunological and employment outcomes.
AB  - BACKGROUND: Little is known about the prognosis of occupational asthma induced by
      high molecular weight proteins. OBJECTIVE: Our objective was to measure the
      clinical, immunological and employment outcomes of individuals with occupational
      asthma induced by detergent enzymes. METHODS: We undertook a workforce-based
      follow-up study in 35 (78%) of the 45 ex-employees from a single factory with
      occupational asthma. In each case the diagnosis was supported by evidence of
      specific sensitization and characteristic changes in peak flow or a positive
      response to specific bronchial provocation testing. RESULTS: This group had left
      the factory on average 37 months before study. On review 25 (71%) reported chest
      symptoms during the last month. Compared with when working at the factory, most
      (86%) reported that their symptoms had improved. Twenty continued to attend their
      general practitioner for respiratory symptoms and 19 still used asthma
      medications. Since leaving the factory 16 (46%) and four (11%) had found full
      time or part-time employment, respectively; of these 16 found they were paid less
      than when they worked at the factory. The remaining 15 subjects had not had any
      paid employment. All but two had positive skin prick tests to one or more three
      detergent enzymes. The estimated half-life of serum-specific IgE antibodies was
      20 months for protease, and 21 months for cellulase and amylase. CONCLUSIONS:
      Population-based follow-up studies of the prognosis of occupational asthma are
      rare but probably avoid the bias in clinic-derived surveys. This study
      demonstrates that 3 years after the avoidance of exposure with detergent enzymes
      most patients continue to be troubled by, albeit improved, symptoms and
      experience difficulty in re-employment.

PMID- 16630154
TI  - Do parents with an atopic family history adopt a 'prudent' lifestyle for their
      infant? (KOALA Study).
AB  - BACKGROUND: Atopic parents may adopt lifestyle characteristics that allegedly
      protect against atopic disease. If this is true, infants from atopic parents will
      be characterized by low-risk behaviour. Consequently, aetiologic studies on
      lifestyle factors and allergic disease in childhood may be biased by confounding
      by indication. OBJECTIVE: We explored whether the prevalence of 'prudent'
      lifestyle characteristics differs between atopic and non-atopic families.
      METHODS: Information about a family history of atopic manifestations and
      lifestyle characteristics was collected by repeated questionnaires in the Dutch
      KOALA Birth Cohort Study in 2469 infants from families with divergent lifestyle
      practices (conventional vs. alternative). RESULTS: In conventional lifestyle
      families, infants were less often exposed to environmental tobacco smoke when
      parents were atopic than when they were non-atopic (10.0% vs. 14.7%, P=0.001). In
      alternative lifestyle families, exposure to smoking was very rare in both groups
      (1.7% vs. 2.6%). Pets were less often present in families with than without
      parental atopy (38.8% vs. 51.1%, P=0.008 for conventional lifestyle families;
      43.0% vs. 48.4%, P=0.014 for alternative lifestyle families). Infants with atopic
      siblings had less often been vaccinated according to the standard scheme than
      infants with non-atopic siblings in conventional lifestyle families (76.6% vs.
      85.5%, P<0.001). In alternative lifestyle families, the difference was in the
      same direction but not statistically significant (30.1% vs. 40.5%, P=0.143).
      Antibiotic use, breastfeeding and consumption of organic foods were unrelated to
      a family history of atopic manifestations. CONCLUSION: Some 'prudent' lifestyle
      characteristics differed between atopic and non-atopic families, depending on
      whether atopic manifestations were present in parents or older siblings. This has
      important consequences for the validity in epidemiological studies on the
      aetiology of allergy in children. Confounding by indication because of a family
      history of atopic manifestations can best be controlled for by considering atopy
      in parents and siblings as separate confounders.

PMID- 16630155
TI  - Inverse association between periodontitis and respiratory allergies.
AB  - BACKGROUND: Periodontitis is an infection with systemic effects and a high
      prevalence among adults. In the aetiology of allergic diseases the hygiene
      hypothesis claims that infections in early infancy may protect against allergic
      diseases. OBJECTIVE: The aim of the present analyses was to investigate the
      independent relation between periodontitis and respiratory allergies such as
      hayfever, house dust mite (HDM) allergy and asthma. METHODS: From the Study of
      Health in Pomerania (SHIP) a total number of 2837 subjects aged 20 to 59 years
      were included in the analysis. In our study population 326, 111 and 114 subjects
      were classified as suffering from hayfever, HDM allergy or asthma, respectively.
      The attachment loss (AL) were measured. Periodontitis was defined according to
      the percentage of surfaces which exceeded 3 mm AL [healthy: 0-7.7%, mild: 7.8
      28.6%, moderate: 28.7-63.9%, severe: >63.9%]. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated using logistic regression. RESULTS:
      After adjustment for confounding factors these analyses revealed inverse
      associations between periodontitis and hayfever as well as periodontitis and HDM
      allergy. For increasing AL, a trend of decreasing risk could be observed for
      hayfever (healthy: reference; mild AL: OR 0.87 [95%-CI 0.6-1.2]; moderate AL: OR
      0.80 [95% CI 0.6-1.2]; server AL: OR 0.53 [95% CI 0.3-0.9]; P(trend)=0.01) and
      for HDM allergy (healthy: reference; mild AL: OR 0.80 [95% CI 0.5-1.3]; moderate
      AL: OR 0.64 [95% CI 0.3-1.2]; server AL: OR 0.39 [95% CI 0.2-0.9];
      P(trend)=0.02). Furthermore, for asthma were observed a slightly inverse
      association in the full-adjusted model (healthy: reference; mild AL: OR 1.10 [95%
      CI 0.6-2.0]; moderate AL: OR 0.96 [95% CI 0.5-1.8]; server AL: OR 0.48 [95% CI
      0.2-1.0]; P(trend)=0.11). CONCLUSION: There is an inverse association between
      periodontitis and respiratory allergies. Our results might support the hygiene
      hypothesis.

PMID- 16630156
TI  - Degree and clinical relevance of sensitization to common allergens among adults:
      a population study in Helsinki, Finland.
AB  - BACKGROUND: We aimed to assess the prevalence of allergic sensitization and
      multiple sensitization, risk factors, and the clinical impact of being sensitized
      in the adult population of Helsinki, Finland. METHODS: As a part of the FinEsS
      study, a population-based random sample of 498 adults aged 26-60 years were
      tested for 15 common aeroallergens with skin prick tests (SPTs) and interviewed
      on respiratory symptoms and diseases, including respiratory irritants and
      childhood environment. RESULTS: The prevalence of at least one positive prick
      test was 46.9%. A large difference by age was found: 56.8% were sensitized among
      those aged 26-39 years, 49.2% in the age group 40-49 years, and 35.6% in the age
      group 50-60 years (P<0.001). Sensitization to multiple allergens was common among
      young subjects with 42% of the sensitized responding to at least four allergens,
      while this proportion was only 16% of the sensitized among those aged 50-60
      years. The prevalence of physician-diagnosed asthma, allergic rhinitis (AR) or
      conjunctivitis, and wheeze increased significantly with increasing number of
      positive responses to SPTs. Having a family history of AR or conjunctivitis was a
      significant risk factor for allergic sensitization and for sensitization to any
      of the pollens. Further, urban living in childhood yielded an increased risk for
      pollen sensitization. CONCLUSIONS: The prevalence of allergic sensitization was
      high in the urban adult population of Helsinki. More than half of those aged 26
      39 years was sensitized and 24% was sensitized to at least four allergens.
      Sensitization to multiple allergens was associated with a high prevalence of
      asthma, AR or conjunctivitis, and wheeze.

PMID- 16630157
TI  - Genetic polymorphisms of major house dust mite allergens.
AB  - BACKGROUND: Polymorphic sequence substitutions in the major mite allergens can
      markedly affect immunoglobulin E binding and T cell responses, but there are few
      studies on environmental isolates from Dermatophagoides pteronyssinus and none
      for D. farinae. OBJECTIVE: To determine the sequence variation of the group 1 and
      2 allergens from environmental D. pteronyssinus and D. farinae. METHODS: RNA from
      each species was isolated from homes in Bangkok and the sequence of Der p 1, Der
      p 2, Der f 1, and Der f 2 determined from cDNA produced by high fidelity
      polymerase chain reactions. RESULTS: The enlarged data set revealed preferred
      amino acid substitutions in residues 19, 81, and 215 of Der p 1 as well as
      sporadic changes. Der p 2 showed frequent variations with clusters of amino acid
      substitutions, but the canonical Der p 2.0101 was not found in any of 17
      sequences. Der f 2 showed variants with clusters of substitutions similar to Der
      p 2 but in different amino acid positions and without any structural concordance.
      Der f 1 in contrast to the other allergens had few amino acid sequence
      substitutions. CONCLUSIONS: The sequence information on variants provides data
      important for the optimal design of allergen formulations and useful for the
      genetic engineering and structure-function analyses of the major allergens.

PMID- 16630158
TI  - Structural, immunological and functional properties of natural recombinant Pen a
      1, the major allergen of Brown Shrimp, Penaeus aztecus.
AB  - BACKGROUND: Recombinant allergens are considered the basis for new diagnostic
      approaches and development of novel strategies of allergen-specific
      immunotherapy. As Pen a 1 from brown shrimp Penaeus aztecus is the only major
      allergen of shrimp and binds up to 75% of all shrimp-specific IgE antibodies this
      molecule may be an excellent model for the usage of allergens with reduced IgE
      antibody-binding capacity for specific immunotherapy. AIM: The aim was to clone,
      express and characterize a full-length recombinant Pen a 1 molecule and compare
      it with natural Pen a 1 in regard to structural and immunological parameters such
      as IgE antibody capacity and ability to induce IgE-mediated mediator release.
      METHODS: Total RNA was isolated from P. aztecus and a rapid amplification of cDNA
      ends (5' RACE) was performed to obtain full-length cDNA coding for Pen a 1. Using
      a gene-specific primer, PCR was performed and full-length cDNA was cloned and
      sequenced. Recombinant His-tagged Pen a 1 was isolated from Escherichia coli
      under native conditions by immobilized metal affinity chromatography. Secondary
      structure of natural and recombinant Pen a 1 was compared by circular dichroism
      (CD) spectroscopy, and the IgE antibody-binding capacity evaluated by RAST. The
      allergenic potency was tested by the capability of natural and recombinant Pen a
      1 to induce mediator release in a murine and human in vitro model of IgE-mediated
      type I allergy. RESULTS: The deduced amino-acid sequence was 284 residues long
      and amino-acid sequence identities with allergenic and non-allergenic
      tropomyosins ranged from 80% to 99% and 51% to 58%, respectively. The analysis of
      the secondary structure of natural and recombinant Pen a 1 by CD spectroscopic
      analysis showed that both nPen a 1 and rPen a 1 had alpha-helical conformation
      that is typical for tropomyosin. The IgE antibody binding capacities of nPen a 1
      and r Pen a1 were found to be essentially identical by RAST. The mediator release
      experiments using both wild-type and humanized rat basophilic leukaemia 30/25
      cells showed that rPen a 1 and nPen a 1 induced a similar level of mast cell
      activation. CONCLUSIONS: Recombinant Pen a 1 and natural Pen a 1 are structurally
      and immunologically identical and rPen a 1 may be used as the basis for component
      resolved diagnosis and the generation of modified shrimp tropomyosin for allergen
      specific immunotherapy. The results of the animal studies indicate that C3H/HeJ
      mice that were sensitized with shrimp extract in combination with cholera toxin
      as adjuvant may be a suitable model to study shrimp allergy.

PMID- 16630159
TI  - Competition enzyme-linked immunosorbant assay (ELISA) can be a sensitive method
      for the specific detection of small quantities of allergen in a complex mixture.
AB  - RATIONALE: The competition ELISA assay is used to determine the potency of US
      standardized allergen extracts. We have been concerned that the competition ELISA
      is not sensitive to changes in individual allergen levels. This study was
      designed to determine the sensitivity of the competition ELISA to detect the
      specific loss of Bla g 1 and Bla g 2 in cockroach extracts. METHODS: German
      cockroach extract E3Cg was made from defatted German cockroaches. New Zealand
      White rabbits were immunized with rBla g 1 or rBla g 2. Optimal dilutions of anti
      Bla g 1 and anti-Bla g 2 sera were established by ELISA. E3Cg was selectively
      depleted of Bla g 1 or Bla g 2 by immunoabsorption with anti-Bla g 1 or anti-Bla
      g 2 attached to Protein G agarose beads. Competition ELISA using pooled human
      sera, or mixed anti-Bla g 1 and anti-Bla g 2 serum, was performed on the depleted
      extracts, and on depleted extracts reconstituted with rBla g 1 or rBla g 2.
      RESULTS: Unlike pooled human-allergic IgE sera, anti-Bla g 1 and anti-Bla g 2 IgG
      -- in dilutions as low as 10(-6), could be used in the competition ELISA to
      measure the loss of allergen in depleted E3Cg. As little as 0.001 microg/mL of
      added rBla g 1 and 0.1 microg/mL of added rBla g 2, could be detected.
      CONCLUSION: The competition ELISA can be highly sensitive to compositional
      differences in complex allergen mixtures, even when the specific detecting
      antibody is present in relatively small amounts.

PMID- 16630160
TI  - In contrast to specific B cells, human basophils are unaffected by the toxic
      activity of an allergen toxin due to lack of internalization of immunoglobulin E
      bound allergen.
AB  - BACKGROUND: Specific immunotherapy is the only curative therapy for type I
      allergies and the alarming increase in allergy prevalence emphasizes the need for
      additional/alternative strategies for curative treatment. Allergen toxins (AT),
      fusion products of an allergen with an apoptosis inducing cytotoxin, are a new
      kind of immunotoxin. OBJECTIVE: AT should allow allergen-specific targeting and
      elimination of allergy-relevant cells, with B cells being the primary target. An
      important question is the fate of the effector cells, e.g. mast cells and
      basophils, which carry allergen-specific IgE: the immunotoxin might even prove to
      be harmful. METHODS: We established a reliable in vitro B cell model (using two
      mouse hybridoma cell lines) for testing specificity and toxicity of P5-ETA', a
      fusion protein of the major timothy grass pollen allergen Phl p 5b and truncated
      Pseudomonas Exotoxin A. In a second step, we investigated the impact of the AT on
      human basophils. RESULTS: P5-ETA' reliably eliminated Phl p 5-specific cells in
      the in vitro B cell model, leaving unspecific B cells unharmed. Human basophils
      of grass pollen allergic donors specifically bound P5-ETA', released IL-4 and up
      regulated the activation marker CD203c, but were not subject to the toxic effect
      because of lack of internalization of IgE-bound allergen. CONCLUSION: According
      to our data, basophils are pure effector cells in the context of IgE-bound
      allergen and not involved in classical antigen presentation.

PMID- 16630161
TI  - The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and
      involved in eosinophil trafficking to the intestine.
AB  - BACKGROUND: Of the numerous adhesion molecules expressed by eosinophils, the
      alpha4-integrin has been identified as critically involved in eosinophil
      trafficking in the lung. Most studies have focused on the role of the alpha4beta1
      adhesion complex, but eosinophils also express the alpha4beta7-integrin complex.
      OBJECTIVE: To investigate the role of alpha4beta7, by assessing its membrane
      expression on eosinophils from different compartments using allergen-challenged
      mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the
      impact of beta7-integrin deficiency on eosinophil recruitment to the lungs and
      intestine in specific experimental allergic models. RESULTS: Evaluation of
      alpha4beta7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue
      eosinophils revealed a down-regulation of this integrin as eosinophils migrate
      through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic
      mice had low expression of the alpha4beta7-complex. While expression of the
      alpha4-chain remained unchanged, a significant decrease in beta7-surface
      expression was observed. Intestinal eosinophils, isolated from Peyer's patches,
      also displayed a down-regulation of the alpha4beta7-integrin, albeit only modest.
      In contrast, circulating eosinophils, isolated from the blood and spleen,
      expressed high levels of the alpha4beta7-integrin. However, eosinophil
      trafficking into the lungs of beta7-integrin-deficient mice was not significantly
      impaired in response to respiratory allergen challenges. In contrast, beta7
      deficient mice had impaired eosinophil recruitment to the intestine. CONCLUSION:
      Taken together, these results identify differential expression of the alpha4beta7
      integrin on eosinophils and its critical role in regulating eosinophil responses
      in the intestine.

PMID- 16630162
TI  - Psychological aspects of pre-symptomatic testing for Machado-Joseph disease and
      familial amyloid polyneuropathy type I.
AB  - Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and
      familial amyloid polyneuropathy type I (FAP-I or ATTR V30M) are neurodegenerative
      disorders, inherited in an autosomal dominant fashion, which have a high
      prevalence in Portugal, probably due to a founder effect. MJD and FAP-I are late
      onset diseases, with symptoms emerging usually during adulthood. CGPP, which is
      the national reference centre for these disorders, has a genetic lab that offers
      diagnostic, pre-symptomatic and prenatal testing and an outpatient clinic to
      counsel and follow relatives at risk for hereditary ataxias, FAP-I and Huntington
      disease (HD). The present work is a review of our 10-year experience with
      psychological counselling of individuals at risk for MJD and FAP-I. Persons at
      risk for FAP-I may show a better response to pre-symptomatic testing than those
      who are at risk for MJD and HD because of the availability of liver
      transplantation, which may improve their health and life expectancy.
      Psychological well-being and specific distress of MJD and FAP-I test applicants,
      before undergoing genetic testing (baseline level) and 3 to 6 months after
      disclosure of test results, have shown a low level of change, both in identified
      carriers and non-carriers. A major goal of psychological characterization of at
      risk individuals for MJD and FAP-I is to determine the factors that influence the
      uptake of genetic testing.

PMID- 16630163
TI  - New developmental insights from high-throughput biological analysis in
      Caenorhabditis elegans.
AB  - The use of Caenorhabditis elegans as a model system for understanding animal
      development and human disease has long been recognized as an efficient tool of
      discovery. Recent developments, particularly in our understanding of RNA-mediated
      interference and its ability to modify gene activity, have facilitated the use of
      C. elegans in determining gene function via high-throughput analysis. These new
      strategies have provided a framework that allows investigators to analyse gene
      function globally at the genomic level and will likely become a prototypic model
      for biological analysis in the post-genome era.

PMID- 16630164
TI  - Inflammatory bowel disease and innate immune response genes: the challenge of
      complex polygenic disorders for the clinical geneticist.

PMID- 16630165
TI  - Clinical profiles of four patients with Rett syndrome carrying a novel exon 1
      mutation or genomic rearrangement in the MECP2 gene.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X
      linked MECP2 gene encoding methyl CpG binding protein 2 (MeCP2). Recently, a new
      isoform of MeCP2 including exon 1 was identified. This new isoform is more
      abundantly expressed in brain than the isoform including exons 2-4. Very little
      is known about the phenotypes associated with mutations in exon 1 of MECP2 since
      only a limited number of RTT patients carrying such mutations have been
      identified so far. In this study, we screened a cohort of 20 girls with RTT for
      exon 1 mutations by sequencing and multiplex ligation-dependent probe
      amplification (MLPA). We identified one girl with a novel exon 1 mutation
      (c.30delCinsGA) by sequencing and three with genomic rearrangements by MLPA.
      Comparison of the phenotypes showed that the girls carrying a mutation or
      rearrangement encompassing exon 1 were more severely affected than the girls with
      rearrangements not affecting exon 1.

PMID- 16630166
TI  - Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a
      meta-analysis.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been
      linked to the risk of developing breast cancer. A meta-analysis of 18 case
      control studies investigating the association between the C677T and the A1298C
      polymorphisms of the MTHFR gene and breast cancer (BC) was carried out. The meta
      analysis included genotype data on 5467/7336 and 3768/5276 cases/controls for
      C677T and A1298C, respectively. In the meta-analysis, the consistency of genetic
      effects across different ethnicities and the effect of menopausal status for
      various genetic contrasts were investigated. The overall analysis for
      investigating the association between the C677T allele T and the risk of
      developing BC showed significant heterogeneity (p = 0.08, I2 = 34%) and non
      significant association [odds ratio (OR) 1.02; 95% confidence interval (0.95
      1.10)]. The allele contrast was not significant in Caucasians (nine studies) and
      in East Asians (four studies) [OR 1.03 (0.93-1.14) and OR 0.96 (0.81-1.15),
      respectively] or in pre-menopausal (five studies) and post-menopausal (four
      studies) groups [OR 1.10 (0.94-1.29) and OR 1.06 (0.95-1.18), respectively]. The
      genotype contrast of the homozygotes (TT vs CC) produced significant results only
      for pre-menopausal cases [OR 1.46 (1.05-2.03)]. The recessive model for allele T
      produced significant association only in pre-menopausal cases [OR 1.49 (1.09
      2.03)]. The dominant model for the effect of allele T produced no significant
      results, overall and in each subgroup. For the A1298C polymorphism, all genotype
      contrasts showed lack of association, overall and in Caucasians. In summary, the
      accumulated evidence supports an association in pre-menopausal women. BC is a
      complex disease with multifactorial etiology, and therefore, case-control studies
      that investigate gene-environment interaction might elucidate further the
      genetics of the disease.

PMID- 16630167
TI  - Successful umbilical cord blood stem cell transplantation in a patient with
      Rothmund-Thomson syndrome and combined immunodeficiency.
AB  - The ATP-dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ
      helicases that are felt to be important in maintaining chromosomal integrity
      (Kitao et al., 1998, Genomics: 54 (3): 443-452). Deletions in the RECQL4 gene
      located on chromosome 8 region q24.3 have been associated with Rothmund-Thomson
      syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse
      hair, small stature, skeletal abnormalities, cataracts and an increased risk of
      malignancy. We present a patient with a molecularly confirmed diagnosis of RTS
      with two unique genetic alterations in RECQL4 (IVS16-2A>T and IVS2+27_51del25),
      who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia.
      Evaluation of his immune system demonstrated a T- B+ NK- phenotype with
      agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to
      evaluate for known genetic causes of CID were not revealing. The patient received
      an umbilical cord blood (UCB) transplant with complete immune reconstitution.
      This report represents the first description of a CID phenotype and UCB
      transplantation in a patient with RTS.

PMID- 16630168
TI  - A successful approach for the detection of Fabry patients in Argentina.
AB  - Fabry disease is an X-linked lysosomal disorder caused by the deficiency of the
      lysosomal enzyme alpha-galactosidase A (alpha-Gal A). In males, the laboratory
      diagnosis is based on the demonstration of decreased levels of alpha-Gal A
      activity, while in females, the disease is diagnosed by the identification of a
      mutation in alpha-Gal A gene. Fabry disease in Argentina is underdiagnosed. To
      date, no comprehensive screening study of Fabry disease in our country has been
      reported. The present study aimed at developing a targeted screening for the
      detection of Fabry patients from Argentina based on the set of typical signs and
      symptoms. We received 121 blood samples from probable Fabry patients for
      enzymatic and genetic assay. We diagnosed six Fabry patients from six unrelated
      families, representing a yield of detection of 4.96%. The mutations detected in
      five of the families analysed were missense mutations: p.Leu243Trp, p.Asp155His,
      p.Leu415Pro, p.Cys94Tyr and p.Leu191Pro. After the detection of a Fabry patient,
      his/her relatives were also screened. In the course of these family studies,
      other 64 Fabry patients, 29 males and 35 females, were detected. To our
      knowledge, this is the first comprehensive screening of Fabry disease in
      Argentina. We detected 70 patients in a period of 2.5 years. The development of
      targeted protocols and the constitution of interdisciplinary groups for the
      identification of patients with Fabry disease are recommended to obtain a higher
      yield in the process.

PMID- 16630169
TI  - LADD syndrome is caused by FGF10 mutations.
AB  - Lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] is an autosomal
      dominant multiple congenital anomaly disorder characterized by aplasia, atresia
      or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing
      loss, and dental and digital anomalies. Loss of function mutations in FGF10 were
      recently described in aplasia of the lacrimal and salivary glands [ALSG (MIM
      180920; MIM 103420)] (Entesarian et al., Nat Genet 2005: 37: 125-127, Milunsky et
      al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005:
      A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG
      and the variable expressivity of both the disorders, we hypothesized that FGF10
      mutations could also result in LADD syndrome. A de novo missense mutation was
      found in exon 3 of FGF10 in a 3-year-old female (Family 1) with LADD syndrome.
      This missense mutation, resulting in a non-conservative amino acid change, was
      confirmed by restriction enzyme digestion and was not found in 500 control
      chromosomes. A nonsense mutation was also found in exon 2 of FGF10 (Family 2) in
      a 19-year-old mother with ALSG and her 2-year-old daughter with LADD syndrome.
      Previous studies of FGF10 mutant mice have demonstrated abnormalities consistent
      with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may
      represent variable presentations of the same clinical spectrum caused by FGF10
      mutations.

PMID- 16630170
TI  - Skin abnormalities as an early predictor of neurologic outcome in Gaucher
      disease.

PMID- 16630171
TI  - Paraoxonase-1 Q192R polymorphism and risk of sporadic amyotrophic lateral
      sclerosis.

PMID- 16630172
TI  - The incidence patterns of Down syndrome in Qatar.

PMID- 16630173
TI  - Late-onset treatment in Menkes disease: is there a correlation between genotype
      and response to therapy?

PMID- 16630174
TI  - Identification of a submicroscopic deletion of SHH associated with the
      holoprosencephaly spectrum by array-based CGH.

PMID- 16630176
TI  - Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic
      classification--part two.
AB  - Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely
      varying clinical behaviors, ranging from indolent to aggressive tumors with
      significant metastatic potential. However, the tendency for pathologists and
      clinicians alike is to refer to all squamoid neoplasms as generic SCC. No
      definitive, comprehensive clinicopathological system dividing cutaneous SCCs into
      categories based upon their aggressiveness has yet been promulgated. Therefore,
      we have proposed the following based upon the malignant potential of SCC
      variants, separating them into categories of low (< or = 2% metastatic rate),
      intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low
      risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC,
      tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation).
      Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal
      epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High
      risk subtypes include de novo SCC, SCC arising in association with predisposing
      factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease,
      adenosquamous carcinoma, and malignant proliferating pilar tumors. The
      indeterminate category includes signet ring cell SCC, follicular SCC, papillary
      SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear
      cell SCC. Subclassification of SCC into these risk-based categories, along with
      enumeration of other factors including tumor size, differentiation, depth of
      invasion, and perineural invasion will provide prognostically relevant
      information and facilitate the most optimal treatment for patients.

PMID- 16630177
TI  - Analysis of protein tyrosine kinases expression in the melanoma metastases of
      patients treated with Imatinib Mesylate (STI571, Gleevec).
AB  - BACKGROUND: Protein tyrosine kinase (PTK) inhibition has been identified as a
      promising strategy in the development of new selective therapies, targeting the
      signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor
      drugs, may have a potential therapeutic benefit in melanoma, which involves
      abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF)
      tyrosine kinases. METHODS: Tumor biopsies from 13 patients with metastatic
      melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related
      gene (ARG), PDGF receptor-alpha (PDGFR-alpha) and PDGFR-beta] expression before
      and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage
      of positive cells and staining intensity were evaluated. RESULTS: We found a
      statistically significant (p < 0.01) selective loss of PTK expression in the
      follow-up biopsy, both in intensity and number of positive cells. PDGFR-alpha and
      -beta had the highest level of expression reduction. One patient had a durable
      clinical response, and the follow-up biopsy showed negative expression for four
      of the PTKs, namely c-abl, ARG, PDGFR-alpha, and beta. CONCLUSIONS: Our study
      reports for the first time the in vivo effect of Gleevec in the induction of
      apparently selective reduction of PTKs expression under anti-tyrosine kinases
      treatment, suggesting its potential role in melanoma treatment.

PMID- 16630178
TI  - t(14;18)(q32;q21) involving IGH and MALT1 is uncommon in cutaneous MALT lymphomas
      and primary cutaneous diffuse large B-cell lymphomas.
AB  - BACKGROUND: t(14;18)(q32;q21) involving IGH and MALT1 has been demonstrated in
      cutaneous MALT lymphomas and in one case of primary cutaneous diffuse large B
      cell lymphoma (DLBCL). However, the incidence of IGH/MALT1 translocations in
      these forms of cutaneous lymphoma remains unclear. METHODS: We performed paraffin
      section interphase fluorescence in situ hybridization (FISH) analysis using MALT1
      and IGH break-apart probes on 16 cutaneous MALT lymphomas and 16 primary
      cutaneous DLBCL in order to assess the frequency of IGH/MALT1 translocations and
      to screen for other potential translocations involving the IGH or MALT1 loci.
      RESULTS: Translocations involving MALT1 were not detected in any of 16 cutaneous
      MALT lymphomas or 16 primary cutaneous DLBCL. Of the 12 MALT lymphomas that could
      be analyzed for an IGH translocation, all were negative. In contrast, four of the
      13 cases (31%) of primary cutaneous DLBCL that could be analyzed for
      translocations involving IGH were positive. Subsequent FISH analysis demonstrated
      one of these to be an IGH/BCL2 translocation and one to be a CMYC/IGH
      translocation, while the translocation partners in the remaining two cases are
      currently unidentified. CONCLUSIONS: This study demonstrates that translocations
      involving MALT1, including IGH/MALT1, are uncommon in cutaneous MALT lymphomas
      and primary cutaneous DLBCL. Other translocations involving IGH also are not
      involved in the pathogenesis of at least most cutaneous MALT lymphomas. In
      contrast, primary cutaneous DLBCL may contain one of several IGH translocations
      in a minority of cases.

PMID- 16630179
TI  - The expression of p63 in basal cell carcinomas and association with histological
      differentiation.
AB  - BACKGROUND: We aim to examine p63 expression in basal cell carcinomas (BCCs) and
      to investigate association with their histopathological differentiation subtypes.
      METHODS: Eighty-four BCCs were classified according to the histopathologic
      differentiation subtypes. Immunohistochemistry using monoclonal antibody against
      p63 was performed. RESULTS: In nontumoral skin, p63 expression was consistently
      seen in basal/suprabasal cells of epidermis, hair matrix cells, and outer root
      sheath of the hair follicle. In BCCs, the cases were distributed as 47
      undifferentiated, 28 differentiated (16 adenoid and 12 keratotic), and nine
      superficial. The nuclear p63 expression was negative in two cases, whereas 64
      BCCs (76.2%) showed homogeneous p63 immunostaining. There was no statistically
      significant difference between p63 expression and histological differentiation
      subtypes (p > 0.05). The expression of p63 was found strongly and diffuse in
      72.3% of solid undifferentiated and 82.1% differentiated and in 77.8% of
      superficial type BCCs. CONCLUSIONS: p63 is consistently expressed in epidermal
      basal/suprabasal and adnexal basal cells. Most BCCs have higher homogeneous p63
      expression than nontumoral epidermis, which is not changed according to
      histological differentiation subtypes. Thus, overexpression of p63 in all
      histological subtypes may confirm that basaloid progenitor cells are linked tumor
      cell lineage and have a role in the tumorigenesis of BCC.

PMID- 16630180
TI  - IgG4 as the predominant IgG subclass in pemphigoides gestationis.
AB  - BACKGROUND: Pemphigoides gestationis (PG) is a blistering disorder of pregnancy
      caused by antibodies against basement membrane proteins. They are directed
      against the 180 kD bullous pemphigoid antigen (BPAg2), towards the epitopes
      within the NC 16A domain. There are many similarities between pemphigoid
      gestationis and bullous pemphigoid (BP), but the literature so far indicated
      different immunofluorescence results in regards with C3 and IgG, and IgG
      subclasses (IgG4 vs. IgG1). METHODS: We evaluated staining patterns and IgG
      subclasses, as well as C5b-9 membrane attack complex (MAC) in 10 pregnant
      patients with PG, using sandwich double antibody immunofluorescence (SDAI) and
      direct immunofluorescence (DIF). RESULTS: All ten specimens stained with C3 by
      DIF, but only five had trace amount of IgG reactants by this method. By SDAI,
      100% were positive for the IgG4 and C5b-9 MAC, 70% for IgG2, 50% for IgG1, and
      40% for IgG3. CONCLUSION: IgG4 was the predominant IgG subtype identified. This
      finding has not been reported for PG, but it mimics results reported for BP. One
      explanation is prolonged disease course, as well as blocking of antigenic domains
      by IgG4. Understanding this completely will help develop therapies and prevention
      strategies for immunobullous and other autoimmune diseases, and perhaps aid in an
      exact classification.

PMID- 16630181
TI  - Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen's
      disease.
AB  - BACKGROUND: Sebaceous carcinoma (SC) is well known for its ability to masquerade
      clinically and histologically as a variety of periocular conditions resulting in
      a delayed diagnosis. We present a series of periocular SC cases and discuss the
      difficulties in histopathological diagnosis when this tumor presents with a
      Bowenoid pattern of intraepithelial spread. METHODS: A retrospective case study
      of all patients with SC of the eyelid treated in our Hospital, from 1997 to 2004,
      was conducted. RESULTS: Eight patients were identified (four females and four
      males). Seven cases involved the upper eyelid. Initial clinical diagnoses
      included blepharitis (three cases), blepharoconjunctivitis (one case),
      cicatrizing conjunctivitis (one case), and lid lesions (two cases).
      Histopathologically, 87.5% of cases were misdiagnosed as Bowen's disease (BD) on
      the initial biopsy. Six of these cases showed no invasive disease on the initial
      biopsy and were eventually found to be invasive SC on subsequent excisions. In
      one case, the tumor was wholly in situ. Delay in diagnosis ranged from 0 to 56
      months. CONCLUSIONS: SC should always be considered in the histological
      differential diagnosis of any eyelid lesion which resembles BD, particularly if
      the upper eyelid is involved or if multivacuolated cytoplasmic clear cell changes
      are seen.

PMID- 16630182
TI  - Colchicine intoxication diagnosed in a skin biopsy: a case report.
AB  - Colchicine toxicity is a rare, but well-described clinical entity. The
      histopathologic findings in various organ systems have been delineated in
      colchicine intoxication; however, skin findings have only been described in rare
      cases. We present a case of colchicine toxicity diagnosed on skin biopsy in a
      patient presenting with mental status changes. Her cutaneous manifestation
      consisted of a diffuse, blanchable, violaceous, morbilliform rash involving the
      trunk and proximal extremities. The histopathologic findings included metaphase
      arrested keratinocytes with underlying basal vacuolization. These features,
      considered in the setting of multiorgan dysfunction and a known exposure of
      colchicine, led to the diagnosis.

PMID- 16630183
TI  - Cutaneous melanoma with pseudomyxoid features.
AB  - A 96-year-old man presented with a polypoid melanoma, which showed a prominent
      clear stroma, similar to that of myxoid melanoma, but stained negative for Alcian
      blue at pH 2.5 and for colloidal iron. It is not clear whether melanoma
      displaying pseudomyxoid features (pseudomyxoid melanoma) may represent a distinct
      histological variant of melanoma. However, it must be differentiated from true
      myxoid melanomas, in which Alcian blue-positive acid mucopolysaccharides are
      present. Urso C. Cutaneous melanoma with pseudomyxoid features.

PMID- 16630184
TI  - Cutaneous neuroendocrine adenoma: an uncommon neoplasm.
AB  - BACKGROUND: Cutaneous neuroendocrine neoplasms are typically malignant. Benign
      cutaneous neuroendocrine tumors are uncommon. METHODS: We report the case of a 32
      year-old female who presented with a granular mass in the right external auditory
      canal. RESULTS: Microscopic examination of a shave biopsy revealed a poorly
      circumscribed neoplasm with glandular differentiation. While cytologic atypia and
      mitotic activity were not evident, pagetoid spread was observed.
      Immunohistochemistry was indicative of neuroendocrine origin. CONCLUSIONS: This
      case report of neuroendocrine adenoma indicates that this entity should be
      entertained in the repertoire of conditions affecting the external ear.

PMID- 16630185
TI  - Atypical fibroxanthoma with perineural or intraneural invasion: report of two
      cases.
AB  - We report two cases of atypical fibroxanthoma (AFX) that both had the previously
      unreported feature of neural invasion (one perineural and the other intraneural).
      AFXs recur in approximately 10% of cases but only rarely metastasize. Features
      associated with recurrence are inadequate excision and invasion into fat.
      Features associated with metastasis include recurrence, vascular invasion, deep
      tissue invasion, and tumor necrosis. Both of these tumors invaded deeply into
      subcutaneous fat and reached the deep fascia. Some authors would regard such
      cases as malignant fibrous histiocytoma (MFH) because of such deep extension;
      however, the concept of AFX as a superficial variant of MFH is outmoded--AFX is a
      distinct clinicopathologic entity with established clinical, histological, and
      immunohistochemical features.

PMID- 16630186
TI  - Multiple mucinous and lipomatous variant of eccrine angiomatous hamartoma
      associated with spindle cell hemangioma: a novel collision tumor?
AB  - Eccrine angiomatous hamartoma (EAH) is a rare, benign condition characterized
      histologically by increased numbers of eccrine elements, as well as numerous
      capillary channels. In most cases, EAH arises as a single lesion; however,
      multiple variants have been reported. We report a 35-year-old female patient with
      multiple, sudoriparous, subcutaneous nodules on the right foot, which showed
      typical histopathological findings of EAH, and vascular components of the tumor
      consisted of thin-walled dilated vascular spaces intermixed with spindle cells
      and some histiocytoid endothelial cells representing spindle cell hemangioma
      (SCH). To our knowledge, the co-existence of EAH with SCH is a novel finding and
      not yet described.

PMID- 16630187
TI  - Cutaneous mesenchymal hamartoma with mixed myogenous differentiation.
AB  - A 3-month-old infant girl presented with a polypoid lesion in the perianal
      region. No changes in this lesion had been noted since birth. Microscopic
      examination of the excised specimen showed a mixture of mesenchymal elements,
      dominated by haphazard thin fascicles of skeletal muscle. Collagen and vascular
      changes were also apparent. Immunohistochemistry showed positive staining for
      muscle-specific actin and desmin in the fascicular components of the lesion, and
      smooth muscle actin, desmin, and h-caldesmon positivity in a haphazard collection
      of muscle fibers in the deep dermis and anal submucosa. Numerous Verhoeff-van
      Gieson positive elastic fibers were also noted. Hamartomas containing skeletal
      muscle have rarely been reported outside of the head and neck region. They must
      be distinguished from a variety of other tumors, including juvenile rhabdomyoma,
      benign Triton tumor, and rhabdomyosarcoma.

PMID- 16630188
TI  - Oral malignant melanoma associated with pseudoepitheliomatous hyperplasia. Report
      of a case.
AB  - BACKGROUND: Pseudoepitheliomatous hyperplasia (PEH), a histological mimic of
      squamous cell carcinoma, is an exuberant reactive epithelial proliferation that
      may be induced by a variety of infectious, traumatic, inflammatory and neoplastic
      conditions of the skin and mucous membranes. PEH has been described in
      association with Spitz nevi and intramucosal nevi but not with oral malignant
      melanoma. METHODS AND RESULTS: A case of PEH in malignant melanoma of the palate
      in a 46-year-old female patient has been described. A search of the English
      literature did not disclose any previously reported case of such event.
      CONCLUSIONS: PEH associated with oral malignant melanoma is apparently very rare
      and most likely originates from the surface epithelium. This is in contrast with
      PEH in cutaneous melanoma where follicular or eccrine units have been suggested
      to be the origin.

PMID- 16630189
TI  - Restoring wisdom to the practice of psychiatry.
AB  - OBJECTIVE: While psychiatry is an exciting and rewarding discipline of medicine,
      the practice of psychiatry has become increasingly simplistic. This address seeks
      to identify some of the influences that underlie this phenomenon. CONCLUSIONS:
      The influences include an increased demand for services and pressure on beds, the
      sway of the pharmaceutical industry with a biological approach being promulgated,
      excessive managerial constraints with an emphasis on efficiency versus
      effectiveness, and the acceptance of DSM diagnostic categories of uncertain
      validity. I argue that we need to rediscover a more wise approach to psychiatric
      practice. We have to insist upon changes to our training such that trainees are
      encouraged to get to know their patients and understand them from a
      biopsychosocial perspective. As a profession, we have to insist on proper care
      for our patients and work with managers and bureaucrats to ensure that the
      management of our patients is centred on quality of care and effectiveness over
      and above efficiency.

PMID- 16630190
TI  - Is real reform of the Medicare Benefits Schedule for psychiatrists in Australia
      economically, socially or professionally desirable?
AB  - OBJECTIVE: To propose alternative Medicare Benefits Schedule-based funding models
      for outpatient psychiatric services in Australia. METHOD: Development of
      alternative funding schedules for a variety of under-serviced populations.
      CONCLUSIONS: Consideration of alternative systems is necessary to address the
      restrictive work practices, inequity and poor distribution of the psychiatric
      workforce.

PMID- 16630191
TI  - The RANZCP Australian Private Practitioners' Network.
AB  - OBJECTIVE: To provide an overview of the challenges and opportunities afforded by
      the practice of psychiatry in the private sector, and in so doing build a
      rationale for the formation of a formally established network of Australian
      psychiatrists who meet to advance constructive proposals concerning the private
      practice of psychiatry, encourage mutual support, and promote this area of
      psychiatric endeavour. CONCLUSIONS: Private psychiatry has dangers, challenges
      and many responsibilities, but it also has the potential for relative
      independence and creative fulfilment. It is desirable that its practitioners
      support each other and work constructively together in addressing the sorts of
      issues delineated in the Private Practitioners' Network's mission statement and
      objectives.

PMID- 16630192
TI  - Psychiatrists in New Zealand: are they burning out, satisfied at work and, in any
      case, who cares?
AB  - OBJECTIVE: To explore possible contributing or mitigating factors for burnout in
      New Zealand psychiatrists as well as future research directions in this area.
      METHOD: A selective review of the literature pertaining to burnout and reports
      regarding New Zealand's medical workforce. RESULTS: Possible factors contributing
      to burnout in New Zealand psychiatrists include rapid changes in the country's
      health system, the challenge of recruiting and retaining psychiatrists, poor
      distribution of staff and funds and difficulties in psychiatric training.
      Potential protective factors against burnout include lifestyle factors, long
      experience in psychiatry, proposed long lengths of career in New Zealand and
      potentially positive changes in the health system. Research challenges include
      subject recruitment, the lack of exploration of personal protective factors and
      completing longitudinal studies. CONCLUSIONS: Given the current state of
      knowledge, it would be difficult to accurately know whether New Zealand
      psychiatrists were burnt out or satisfied with their work. Carefully designed
      studies would help to clarify this issue.

PMID- 16630193
TI  - Social engineers and bystanders: the limits of 'responsibility' in Indigenous
      affairs.
AB  - OBJECTIVE: A significant shift is occurring in Australian Indigenous affairs.
      Contentiously, key Aboriginal and Torres Strait Islander leaders have challenged
      governments and organizations, both mainstream and Indigenous, to confront
      'passive welfare dependence'. This paper explores some of the social justice
      implications and considers the roles of non-Indigenous professionals. METHODS: A
      publication by Pat Dodson and Noel Pearson is used to frame the discussion.
      RESULTS: Ambiguity surrounding a number of key concepts and the shifting
      territory of Indigenous rights has contributed to bureaucratic inertia in
      Indigenous affairs. A range of 'new' concepts is being introduced into the
      current debate, such as expectancy, reciprocity and mutual obligation,
      challenging ideas of responsibility, agency and the roles played by non
      Indigenous bureaucrats and practitioners. CONCLUSIONS: Regardless of good
      intentions or social justice motivations, non-Indigenous interventions must be
      informed by an awareness of the potential to undermine Indigenous agency and,
      consequently, cause harm.

PMID- 16630194
TI  - Tools and methodologies for investigating the mental health needs of Indigenous
      patients: it's about communication.
AB  - OBJECTIVE: To undertake a needs analysis to determine the quality and
      effectiveness of current mental health services to Indigenous patients within a
      health district of Southern Queensland. The present study focused on identifying
      gaps in the service provision for Indigenous patients. Tools and methodologies
      were developed to achieve this. METHOD: Before commencement of the needs
      analysis, a review of related national projects was completed. The needs analysis
      entailed the development and distribution of two separate questionnaires. A major
      priority of the questionnaire for Indigenous patients was ensuring that effective
      communication and cultural respect was achieved. A steering committee of both
      Indigenous and non-Indigenous experts collaborated on this. The second
      questionnaire was for employees of the mental health service. Both questionnaires
      were designed to provide a balanced perspective of current mental health service
      needs for Indigenous people within the mental health service. RESULTS: The
      predominant issue that emerged and underpinned all the results was communication.
      CONCLUSIONS: The present study has developed and used procedures for undertaking
      research involving Indigenous people. It has shown the importance of involving
      Indigenous people to help ensure successful communication, compliance and
      cooperation by Indigenous mental health patients.

PMID- 16630195
TI  - Selecting patients for long-acting novel antipsychotic therapy.
AB  - OBJECTIVE: As new psychopharmacological agents for the management of
      schizophrenia are introduced into clinical practice, inappropriate patient
      selection may often lead to disappointing outcomes for the patient, the family
      and services. Recently, the first and only long-acting novel antipsychotic was
      made available in Australia. Based on criteria used in a large clinical network
      in Victoria, this paper sets out to present six selection profiles for patients
      with schizophrenia who may be suitable candidates for treatment with this class
      of medication. CONCLUSIONS: Optimizing outcome for patients with enduring
      psychotic disorders involves enabling a stable psychopharmacological platform
      upon which to build a psychosocial therapies programme. Too often, problems with
      adherence undermine the recovery process. Long-acting novel antipsychotics ensure
      adherence, with all the advantages inherent in second-generation antipsychotics.
      Identifying patients a priori who might best respond to the long-acting novel
      antipsychotics may lead to improving the efficiency of the recovery process.

PMID- 16630196
TI  - Data collection in consultation-liaison psychiatry: an evaluation of Casemix.
AB  - OBJECTIVE: To evaluate the usefulness of Casemix as a data collection system for
      consultation-liaison psychiatry services. METHOD: Health information staff were
      requested to code psychiatric assessments and diagnosis prospectively for
      admissions to the Alfred Hospital, Melbourne, between July 2002 and June 2004
      using Casemix. RESULTS: Psychiatric assessments were requested on 2.5% of all
      hospital admissions (n = 2575). Casemix provided extensive demographic and
      hospital unit data for referred patients, is easy to set up, and is cost-free for
      the psychiatry service. CONCLUSIONS: Casemix can provide extensive meaningful
      data for consultation-liaison psychiatry services that could assist in the
      argument for greater funding of these services.

PMID- 16630197
TI  - Consultation-liaison psychiatry services to nursing homes.
AB  - OBJECTIVE: The aim of the present paper is to review current opinion relating to
      the provision of mental health consultation to nursing homes, and to provide
      recommendations for future research. METHOD: The current literature pertaining to
      consultation-liaison psychiatry within nursing homes was reviewed. RESULTS: There
      is a paucity of well-designed empirical studies of mental health service
      provision to Australian nursing homes. This is of particular concern given the
      ageing Australian population and the prevalence of psychiatric symptoms in
      nursing home residents. Psychiatric consultation and liaison to nursing homes may
      result in reduced need for crisis intervention, improved use of behavioural
      management strategies for the symptoms associated with dementia, and reduced
      nursing home staff stress and burnout. CONCLUSIONS: Further research is required
      to evaluate the costs and benefits of providing regular mental health services to
      nursing homes in Australia, particularly in rural areas. Future service
      development should be complemented by methodologically sound evaluation.

PMID- 16630198
TI  - Education system discrimination against children with mental disorders.
AB  - OBJECTIVE: To describe the conceptual confusion, inconsistency and discrimination
      within some state and territory education systems towards children with mental
      disorders. CONCLUSIONS: Reforms are required to achieve a consistent Australia
      wide framework for the classification of childhood mental disorders as
      disabilities. The mental health diagnostic assessment to qualify for disability
      status needs to be simplified when participation in complex evaluation procedures
      is not possible.

PMID- 16630199
TI  - Video-linked court liaison services: forging new frontiers in psychiatry in
      Western Australia.
AB  - OBJECTIVE: To describe the use of videoconferencing that is providing a
      specialist forensic service to remote parts of Western Australia. CONCLUSIONS:
      Court liaison has been shown to be an effective intervention for people with
      mental illness within the justice system. Most such programmes occur within
      metropolitan areas in Australia. Videoconferencing facilitates the provision of
      specialized forensic services to courts in remote parts of Australia.

PMID- 16630200
TI  - Developing new services for eating disorders: an evaluation study.
AB  - OBJECTIVE: This paper aims to evaluate the structures and processes of eating
      disorders services in two regional cities in Australia. METHOD: Stakeholder
      evaluation undertaken between 2002 and 2005 uses interviews, questionnaires and
      service delivery data to examine: structure and patient profile of the two
      services, barriers and success factors and local factors influencing development
      of the services. RESULTS: The Bendigo service provided secondary consultation and
      specialist management with upskilling of primary care workers as a key goal.
      Patients were referred to the service via mental health triage. The Geelong
      service initially offered assessment only, with direct access for the general
      public. Treatment was offered from early 2004. The Bendigo service assessed 41
      patients, 63% were diagnosed with anorexia nervosa or bulimia nervosa. Most
      patients had a moderate or severe eating disorder. The Geelong service assessed
      186 patients, 55% were diagnosed with anorexia nervosa or bulimia nervosa and 80%
      of this subset had not previously been treated for an eating disorder. General
      practitioners identified barriers to development of the services as: problems
      with capacity building and unrealistic expectations. The success factors were
      providing a locally based service with credible clinicians and effective
      communication. CONCLUSIONS: Activity analysis demonstrates that the goals for
      both services were met. There is a need to measure both short- and long-term
      patient outcomes in order to fully assess effectiveness and applicability to
      other settings. Local factors, such as availability of specialist providers,
      would need to be taken into account.

PMID- 16630201
TI  - Extended Matching Questions and the Royal Australian and New Zealand College of
      Psychiatrists written examination: an overview.
AB  - OBJECTIVE: To provide an overview, for trainees and fellows, of the Extended
      Matching Question, a new question type recently introduced in the Royal
      Australian and New Zealand College of Psychiatrists written examination. The
      characteristics, technical aspects and construction of these question types are
      discussed. Some pointers for candidates and those setting questions are outlined.
      CONCLUSIONS: Extended Matching Questions are now commonly used to test medical
      knowledge in many areas of medicine, including psychiatry. They represent a
      transparent, evidence-based approach to the assessment of medical knowledge,
      which lends itself to electronic marking and statistical analysis. These
      questions facilitate the development of question banks and provide an easily
      accessible oversight of what areas of the curriculum have been examined.

PMID- 16630202
TI  - On being a supervisor: the importance of feedback and how to give it.
AB  - OBJECTIVE: We outline some of the dominant opinions regarding the provision of
      formative feedback, as expressed by both trainees and their supervisors. METHODS:
      Trainee psychiatrists and their supervisors were interviewed and asked to
      identify 'good' as opposed to 'poor' supervision. RESULTS: A recurrent theme in
      interview data was that of formative feedback. Trainees expressed a desire to
      receive it, but some supervisors discussed misgivings and a lack of skill in
      providing such feedback. CONCLUSIONS: Formative feedback is an essential part of
      the supervisor's role. We describe the principles of how to best deliver
      feedback, in order to increase supervisors' confidence and ability in utilizing
      this learning and teaching skill.

PMID- 16630203
TI  - From golden beaches to the heartland: reflections of NSW rural trainees.
AB  - OBJECTIVE: To describe the training experiences of rural-based psychiatry
      trainees in New South Wales. METHOD: Semistructured interviews were conducted
      with psychiatry trainees, rural psychiatrists and rural mental health
      administrators. The interviews were, for the most part, conducted face to face.
      RESULTS: Three factors that make this programme work are the opportunity to start
      training in a rural centre, a local psychiatrist who can act as guide and mentor
      and the initiative of this group of registrars. Three obstacles are a perceived
      lack of flexibility in College guidelines, isolation from peers and insufficient
      support when relocating to the city for specialty terms. CONCLUSIONS: The NSW
      rural psychiatry training project is an exciting development. Three years on, it
      represents the best avenue for creating a locally based rural psychiatrist
      network. It stands as a model for the rest of the country.

PMID- 16630204
TI  - Evaluation of a short course in psychiatry for general practitioners.
AB  - OBJECTIVE: To assess the acceptability and benefits to general practitioners
      (GPs) of a short course on the management of depression and anxiety. METHOD: One
      hundred and twenty-two GPs from southeast metropolitan Melbourne participated in
      a five-session short course. Pre- and post-measures of knowledge, attitude and
      self-evaluated clinical practice and a post-measure of participant satisfaction
      were completed. RESULTS: The course was overwhelmingly appreciated by
      participating GPs. In the group as a whole, knowledge, attitude and certain
      elements of clinical practice changed in a positive and predicted direction.
      General practitioners affirmed the use of an interpersonal and problem-solving
      framework for patients more commonly than a cognitive-behavioural one.
      CONCLUSIONS: Brief educational interventions are useful and, through improving GP
      knowledge, attitude and clinical practice, have an important role to play in
      enhancing the capacity of GPs to assist people with depression and anxiety.

PMID- 16630205
TI  - Transcranial magnetic stimulation in adolescent depression.
AB  - OBJECTIVE: There are few safe and effective biological treatments for major
      depression in adolescents. We aimed to report the use of repetitive transcranial
      magnetic stimulation (rTMS) as a treatment for adolescents with this condition.
      METHODS: The first two subjects in a double-blind, sham-controlled trial of rTMS
      that is evaluating the efficacy and safety of rTMS in depressed adolescents are
      described. Clinical response was assessed at baseline and at the end of each
      week. The following scales were used: Montgomery-Asberg Depression Rating Scale,
      Clinical Global Impression-Severity Scale, Beck Depression Inventory and Centre
      for Epidemiological Studies - Depression - Child Scale. A battery of cognitive
      tests was also used at several intervals to measure potential change in
      neuropsychological functioning. RESULTS: Random allocation of both subjects was
      to active treatment. Both subjects improved to a clinically significant degree
      with rTMS treatment and reported no adverse effects. Neuropsychological testing
      did not demonstrate any deterioration in the domains of functioning tested.
      CONCLUSIONS: Repetitive transcranial magnetic stimulation shows early promise as
      a treatment for major depression in adolescents. Well-designed, sham-controlled
      studies are now indicated to test the efficacy and safety of rTMS in these
      patients.

PMID- 16630206
TI  - Drug-induced psychosis associated with crystalline methamphetamine.
AB  - OBJECTIVE: A case of drug-induced psychosis related to crystalline
      methamphetamine is described, highlighting the phenomenology and relevant
      treatment. RESULTS: A 44-year-old woman with borderline personality traits and
      severe drug dependence developed a protracted drug-induced psychosis related to
      chronic high-dose crystalline methamphetamine use. Complete resolution of
      symptoms occurred with antipsychotic medication and abstinence from
      methamphetamine. Rapid recurrence of symptoms occurred at a time of high stress
      associated with minimal methamphetamine use and cessation of low-dose quetiapine.
      Symptoms rapidly resolved with abstinence, quetiapine and reduction of stressors.
      CONCLUSIONS: A drug-induced psychosis resembling paranoid schizophrenia can occur
      with repeated or high-dose use of methamphetamine. While this generally resolves
      rapidly with cessation of stimulant use, some cases of protracted drug-induced
      psychosis in vulnerable individuals have been documented. Behavioural
      sensitization can also occur, and neuroleptics may prevent the recurrence of
      further psychosis triggered by ongoing low-dose methamphetamine use.

PMID- 16630209
TI  - Access to longitudinal data on mentally ill patients.

PMID- 16630210
TI  - Clinical documentation.

PMID- 16630211
TI  - Hepcidin: an important new regulator of iron homeostasis.
AB  - Summary Hepcidin is an important and recently discovered regulator of iron
      homeostasis. There is strong evidence in support of an important role for
      hepcidin dysregulation in the pathogenesis of iron overload disorders, and
      possibly in the aetiology of the anaemia of chronic disease. Further research is
      needed into the physiology of hepcidin to elucidate the relative contributions of
      the liver and kidney to its production and metabolism. The study of the
      differential roles of prohepcidin and its metabolites as well as the significance
      of their serum and urine levels will enhance our understanding of their role in
      iron metabolism.

PMID- 16630212
TI  - Implementation of monoclonal antibody fluorescence on the Abbott CELL-DYN
      Sapphire haematology analyser: evaluation of lymphoid, myeloid and platelet
      markers.
AB  - Apart from qualitative flags, that are typically inefficient and uninformative,
      haematology instruments provide little meaningful information about lymphocyte
      populations or the lineage of atypical or immature elements, The CELL-DYN
      Sapphire haematology analyser uses integrated optical and fluorescence (488 nm)
      measurements, with FL1 (FITC) and FL2 (PE) detectors being configured for
      fluorescent analysis. As monoclonal antibodies (Mab) are widely used as cellular
      probes, and are likely to constitute the future basis for immunodifferentials, we
      explored the feasibility of implementing immunofluorescence on this routine
      haematology analyser. An extensive series of Mab (CD2, CD3, CD4, CD8, CD11b,
      CD13, CD14, CD16, CD19, CD22, CD33, CD34, CD41, CD42b, CD45, CD56, CD61, CD64,
      CD235a and HLA-DR) were tested singly or in FITC/PE combinations. Analyser
      processing and data acquisition was achieved using CD-Sapphire automated CD61
      immunoplatelet or CD3/4/8 assay procedures and, apart from mixing EDTA-blood and
      antibody, no further sample manipulation was required. Downloaded raw files were
      processed with cytometry software, and all evaluated reagents showed population
      discrimination analogous to flow cytometry. Practical procedures were
      straightforward and required minimal operator training. Extended information that
      can be obtained from monoclonal antibodies with a routine haematology analyser
      has the potential to extend haematology laboratory practices and positively
      impact laboratory and clinical efficiency.

PMID- 16630213
TI  - Complete blood count parameters for healthy, small-for-gestational-age, full-term
      newborns.
AB  - No previous study has investigated the full range of complete blood count (CBC)
      parameters in small-for-gestational-age (SGA) newborns. The main aim of this
      study was to compare CBC and peripheral smear parameters in term, healthy SGA
      neonates and appropriate-for-gestational-age (AGA) neonates, and to establish CBC
      reference values for full-term SGA newborns. One hundred thirty-two healthy, term
      newborns (73 SGA and 59 AGA) were included. On day 1, we obtained 109 samples and
      on day 7 we obtained 77 samples. A CBC and peripheral smear were analyzed for
      each sample collected and group data were compared. We observed higher mean
      values for normoblast count, hemoglobin, hematocrit, and red blood cell (RBC)
      count in the SGA babies than in the AGA babies on day 1. The mean corpuscular
      hemoglobin and mean corpuscular hemoglobin concentration values for the SGA
      babies were decreased because of the relatively high RBC count and relatively
      high mean corpuscular volume we observed in this group. Of the SGA newborns,
      21.9% had neutropenia and 4.7% had absolute neutrophil counts lower than
      1500/microl on day 1. On both day 1 and day 7, the SGA newborns had higher mean
      absolute metamyelocyte counts and higher mean I : T (immature : total neutrophil
      ratio) values than the AGA group. The SGA babies had a lower mean absolute
      lymphocyte count on day 7 than the AGA group. We detected thrombocytopenia in
      almost one-third of the 64 SGA newborns tested on day 1. In summary, our study
      clearly demonstrates that CBC parameters for healthy, full-term, SGA newborns are
      different from those of healthy, term AGA newborns. This is the first study that
      has documented different mean corpuscular volume, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, metamyelocyte counts, lymphocyte
      counts, and I : T in SGA babies compared with AGA babies.

PMID- 16630214
TI  - The laboratory diagnosis of lupus anticoagulant in patients on oral
      anticoagulation.
AB  - Laboratory-specific cut-off lupus ratios (LR), above which a plasma is judged
      positive for lupus anticoagulant (LA), were established for both activated
      partial thromboplastin time-based and dilute Russell viper venom time-based
      methods. The validity of using these cut-off values to determine the presence of
      LA in patients on oral anticoagulation (OAC) was assessed. A cohort of 40
      patients (23 male and 17 female), aged 22-84 years (mean 52 years) were tested
      for LA at the time of a thrombotic event. Repeated testing was performed after
      the same patients were treated with OAC (international normalized ratio 2.0-3.5).
      For 36 patients (90%), LA status was unchanged pre- and on-OAC. Thirteen of the
      40 patients (32.5%) were positive for LA both pre- and on-OAC. Of the 27 patients
      negative for LA pre-OAC, 23 remained negative on-OAC. The four discordant results
      were interesting in that LA positivity was demonstrated only after the patient
      was stable on-OAC. In our cohort of 40 patients, there was a trend for LRs to
      decrease on-OAC, but this did not reach statistical significance. The subset (4)
      went against this trend and became positive after the thrombotic event.

PMID- 16630215
TI  - Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese
      patients with deep venous thrombosis and pulmonary embolism.
AB  - Venous thromboembolism (VTE) is a common vascular disease that results in two
      major clinical manifestations: deep venous thrombosis (DVT) and pulmonary
      embolism (PE). Several genetic risk factors, especially factor V Leiden and
      prothrombin G20210A mutations have been reported to be related to VTE in
      Caucasians, but the relationship remains controversial in other populations.
      Thus, the objective of the present study was to compare the frequency of the two
      mutations and also to investigate whether acquired risk factors other than
      genetic mutations may play a different role in Chinese VTE patients. Thirty-five
      patients were diagnosed with DVT concomitant PE, 178 patients with DVT, 54
      patients with PE and 102 control subjects were recruited. The mutation was
      determined by the polymerase chain reaction-restriction fragment length
      polymorphism method. Of all subjects, none was a carrier of factor V Leiden or
      prothrombin G20210A mutations. The frequency of surgery was significantly higher
      in the PE group than that in other groups. There was no significant difference
      among the three groups in other known risk factors. The data presented here
      indicate that factor V Leiden and prothrombin G20210A mutations are very rare in
      the Chinese population, and the genetic risk profile of VTE in the Chinese
      population is different from that in Caucasians.

PMID- 16630216
TI  - Point-of-care testing of neonatal coagulation.
AB  - The aim of this validation study was to compare prothrombin time (PT) and
      activated partial thromboplastin time (APTT) results from a point-of-care testing
      (POCT) device (Rapidpoint Coag) with those from standard laboratory tests. The
      subjects were newborn infants needing coagulation screen for any clinical
      indications within a regional neonatal intensive care unit. The level of
      agreement between POCT and laboratory measurements of PT and APTT was determined.
      For PT: the bias was from -7.6 to 12.4 s and precision was 5.0 s. For the
      detection of prolonged PT at a level of 16 s, the sensitivity was 0.70,
      specificity was 0.57 and the positive predictive value (PPV) was 0.62. For APTT:
      the bias was from -39.1 to 23.7 s, and precision was 15.7 s. For the detection of
      prolonged APTT at a level of 55 s, the sensitivity was 0.80, specificity was 0.95
      and the PPV was 0.80. The POCT device tested has limited utility as a cot-side
      device for screening for a prolongation of the APTT in the newborn but is not
      sensitive for screening for prolongation of the PT.

PMID- 16630217
TI  - Can oral anticoagulation be managed using telemedicine and patient self-testing?
      A pilot study.
AB  - We report a feasibility study of patient self-testing telemedicine for
      anticoagulant management using TOPCARE (Telematic Homecare Platform in
      Cooperative Health Care Provider Networks, developed by the European Commission
      for a user-friendly information society). TOPCARE comprises a Home Telematic Box
      (TOPCARE BOX), a central database held on a remote server and secure computer
      terminals in the anticoagulant clinic. The TOPCARE BOX transmits encrypted
      International Normalized Ratio (INR) results from the CoaguChek S monitor (Roche
      Diagnostics) via the patient's telephone line to the database, which is accessed
      by health-care professionals via the Internet. The database displays the
      patient's anticoagulant record, highlighting out of range results, overdue tests
      and quality control results. The database can also send information back to the
      TOPCARE box, although currently only the next test date can be transmitted. 23
      patients, on long-term oral anticoagulation were recruited from the hospital
      anticoagulant clinic. After completing a nurse-led training course, patients
      tested their INR weekly on a CoaguChek S and transmitted their results via the
      TOPCARE BOX. The nurse specialist accessed the patient's results, electronically
      entered the date of the next test. Changes in warfarin dose were telephoned. Four
      patients dropped out early in the study and 19 patients received TOPCARE BOXs of
      which nine were fully functional. Unintentional software misconfiguration meant
      that remaining 10 TOPCARE BOXs were nonfunctional (these were later reconfigured
      but not reintroduced into the study). Patients successfully transmitted 222
      results over a 5-month period using the TOPCARE system. Early server problems
      were resolved, but intermittent problems with database access persisted and five
      results were not received by the server. Although concerns were raised regarding
      technical problems, feedback from patients and staff was favourable and the
      system thought to be user-friendly. In conclusion, this pilot study showed that
      telemedicine is a feasible option for anticoagulant management, but that the
      technology requires thorough testing prior to installation.

PMID- 16630218
TI  - PML-RARalpha fusion gene transcripts and biological features in acute
      promyelocytic leukemia patients.
AB  - Acute promyelocytic leukemia (APL) is characterized by the presence of
      rearrangements involving the retinoic acid receptor alpha (RARalpha) gene and a
      variable incidence in different populations. The hybrid gene PML-RARalpha,
      present in 98% of cases, encodes a fusion protein essential to the pathogenesis
      of the disease. Depending of the PML's gene breakpoint in chromosome 15, the
      transcript subtypes bcr1, bcr2 and bcr3 may be formed. The correlation between
      these transcript subtypes and clinical parameters is still controversial. The
      objective of this study was to determine the frequencies of the PML-RARalpha
      transcripts and subtypes in a series of 32 APL patients from Northeast Brazil and
      to evaluate the association of these subtypes to different parameters. The method
      used was RT-PCR. The frequency of our APL cases is approximately 28% of the acute
      leukemias. The results showed the presence of PML-RARalpha isoform in all
      patients and a higher frequency of the bcr1/2 subtype. No significant statistical
      association was found between molecular subtypes and age, sex, French-American
      British (FAB) classification, leukocyte and platelet count, hemoglobin level or
      coagulation tests. In conclusion, these data suggest similar molecular and
      biological features for our APL patients at diagnosis in comparison with those
      reported in current scientific literature.

PMID- 16630219
TI  - Aspergillus brain abscess in a patient with acute myeloid leukaemia successfully
      treated with voriconazole.
AB  - Cerebral aspergillosis is associated with very high mortality in
      immunocompromised hosts. Conventional antifungal agents like amphotericin-B and
      itraconazole are almost ineffective in cerebral aspergillosis. Newer azoles have
      been shown to penetrate the blood, cerebrospinal fluid barrier and achieve
      effective fungicidal concentrations. These newer azoles may change the outlook of
      this fatal condition. We report here a patient with cerebral aspergillosis who
      was successfully treated with voriconazole.

PMID- 16630220
TI  - Recovery of normal autologous myelopoiesis after graft rejection following
      allogeneic bone marrow transplant for agnogenic myeloid metaplasia.
AB  - Allogeneic hematopoietic transplantation is the only currently available therapy
      that has the potential to cure agnogenic myeloid metaplasia (AMM) or primary
      myelofibrosis (PMF). Amelioration of fibrosis and eradication of the abnormal
      clone is thought to occur through the repopulation of marrow by donor-derived
      hematopoiesis and graft-vs.-host reaction leading to graft vs. tumor effect. We
      report here a 50-year-old female with AMM/PMF, conditioned with busulfan and
      cyclophosphamide, who rejected a single locus (HLA-B) mismatched bone marrow
      transplant from her daughter, but recovered normal autologous hematopoiesis with
      disappearance of marrow fibrosis and extramedullary hematopoiesis. Variable
      number tandem repeats (VNTR) analysis showed a gradual loss of donor-derived
      hematopoietic cells with recovery of autologous hematopoiesis. This case
      therefore illustrates that eradication of AMM/PMF in this patient with
      myeloablative chemotherapy combined with a transient allogeneic effect was
      sufficient to suppress the abnormal stem cell clone associated with AMM/PMF with
      subsequent cure.

PMID- 16630221
TI  - Coexistence of light chain disease and chronic lymphocytic leukaemia, a complex
      karyotype with a rapid fatal outcome.
AB  - We report on a 48-year-old man with concomitantly diagnosed kappa expressing
      chronic lymphocytic leukaemia (CLL) and lambda light chain disease with highly
      complex chromosomal aberrations. The clinical course of the disease was very
      aggressive with survival of only 1 month. We demonstrate the distinct clonal
      origin by cytogenetic data and immunoglobulin rearrangement studies. To our
      knowledge this is the first report of a light chain disease associated with CLL.

PMID- 16630222
TI  - Adult T-cell leukemia/lymphoma in a 21-year-old man.
AB  - Adult T-cell leukemia/lymphoma (ATL) is malignancy of mature T cells that caused
      by infection with human T-cell leukemia virus type I (HTLV-I). Leukemogenesis of
      ATL cells considered to involve a multistep oncogenic process, resulting in a
      very long latency period. But, we report here the case of a 21-year-old man
      having suffered from recurrent stomatititis who has already developed acute-type
      ATL. ATL generally occurs after a long latency period, and the present case in a
      young man is thus very rare.

PMID- 16630223
TI  - Persistent nucleated red blood cells in peripheral blood is a poor prognostic
      factor in patients with multiple organ failure.

PMID- 16630225
TI  - Small bowel inflammation in ulcerative colitis.

PMID- 16630226
TI  - Which is the optimal bowel preparation for colonoscopy - a meta-analysis.
AB  - OBJECTIVE: To assess which bowel preparation agent is most effective. METHODS: A
      search of randomized trials between January 1990 and July 2005 was obtained,
      using MEDLINE and PubMed databases, and the Cochrane Central Register of
      Controlled Trials. Meta-analysis was performed using the Forest plot review.
      RESULTS: Sodium phosphate (NaP) was more effective in bowel cleansing than
      polyethylene glycol (PEG) - odds ratio 0.75 (95%CI: 0.65-0.88; P = 0.0004); and
      sodium picosulphate (SPS) - odds ratio 0.52 (95%CI: 0.34-0.81; P = 0.004). PEG
      and SPS were comparable in bowel cleansing ability, odds ratio 1.69 (95%CI: 0.92
      3.13; P = 0.09). NaP was more easily completed by patients compared to PEG, odds
      ratio 0.16 (95%CI: 0.09-0.29; P < 0.00001). More patients were able to complete
      SPS than PEG, but this was not statistically significant - odds ratio 0.56
      (95%CI: 0.28-1.13; P = 0.11). NaP and PEG were comparable in terms of adverse
      events, odds ratio 0.98 (95%CI: 0.82-1.17; P = 0.81), although NaP resulted in
      more asymptomatic hypokalaemia and hyperphosphataemia. NaP and SPS appeared to
      have similar incidence of adverse events. PEG resulted in more adverse events
      than SPS, odds ratio 3.82 (95%CI: 1.60-9.15; P = 0.003). CONCLUSIONS: NaP was
      more effective in bowel cleansing than PEG or SPS and was comparable in terms of
      adverse events. Patients have more difficulty completing PEG than NaP and SPS.
      Biochemical changes associated with a small-volume preparation like NaP, albeit
      largely asymptomatic, mandate caution in patients with cardiovascular or renal
      impairment.

PMID- 16630227
TI  - Drainage or nondrainage in elective colorectal anastomosis: a systematic review
      and meta-analysis.
AB  - BACKGROUND: There is little agreement on prophylactic use of drains in
      anastomoses in elective colorectal surgery despite many randomized clinical
      trials. Once anastomotic leakage occurs it is generally agreed that drains should
      be used for therapeutic purposes. However, on prophylactic use no such agreement
      exists. AIM: To compare the safety and effectiveness of routine drainage and
      nondrainage regimes after elective colorectal surgery. The primary outcome was
      clinical anastomotic leakage. METHODS: A systematic search was undertaken to
      identify randomized clinical trials. Of the 1140 patients who were enrolled (six
      randomized controlled trials), 573 were allocated for drainage and 567 for no
      drainage. Outcome measures were: (i) mortality: 3% (18 of 573 patients) compared
      with 4% (25 of 567 patients); (ii) clinical anastomotic dehiscence: 2% (11 of 522
      patients) compared with 1% (7 of 519 patients); (iii) radiological anastomotic
      dehiscence: 3% (16 of 522 patients) compared with 4% (19 of 519 patients); (iv)
      wound infection: 5% (29 of 573 patients) compared with 5% (28 of 567 patients);
      (v) reintervention: 6% (34 of 542 patients) compared with 5% (28 of 539
      patients); (vi) extra-abdominal complications: 7% (34 of 522 patients) compared
      with 6% (32 of 519 patients). None of these differences in outcome was
      significant. CONCLUSION: There is insufficient evidence showing that routine
      drainage after colorectal anastomoses prevents anastomotic and other
      complications.

PMID- 16630228
TI  - A five-year audit of anal cancer in Wales.
AB  - OBJECTIVES: A retrospective audit has been undertaken of Squamous (epidermoid)
      type of anal cancer diagnosed and treated in the principality of Wales over a
      five-year period (1995-99) with follow-up until 2005. The referral pattern,
      distribution, presenting symptoms, predisposing conditions, clinical findings and
      staging modalities were documented. The surgical and oncological treatment
      together with their outcome was analysed. METHODS: Patients were identified from
      the Welsh Cancer Registry and the pathology databases of the 17 acute hospitals
      in Wales. Data was collected from the clinical and oncology case notes onto a
      purpose designed Microsoft access database. RESULTS: There was a wide variation
      in data quality from the individual units. Twenty-six anal cancers were diagnosed
      per year in the region. Median age was 69 years. Ten percent had documented
      perianal Human Papilloma Virus related disease. Radiology was inconsistently used
      for staging. Eighty percent were referred for an oncology opinion; 50% had chemo
      radiotherapy with a curative intent. The over-all Stoma rate was 35% and of these
      18% had an abdomino perineal resection. The overall five-year survival was 45%.
      CONCLUSIONS: This is a unique regional audit of anal cancer. Improvements need to
      be made in documentation particularly of staging, treatment, pathology reporting
      and outcome. This study concurs that Human Papilloma Virus appears to predispose
      to Squamous anal cancer. Radiological staging needs to be standardized according
      to best clinical practice. As recommended by NICE all patients should be referred
      to a multidisciplinary anal cancer team, which can provide individual treatment
      plans. Increased specialization could mean specialist regional MDTs for anal
      cancer.

PMID- 16630229
TI  - Sub-specialization in general surgery: the problem of providing a safe emergency
      general surgical service.
AB  - BACKGROUND: The increasing subspecialization of general surgeons in their
      elective work may result in deskilling and create problems in providing expert
      care for emergency cases. To evaluate the size of the problem this study
      determined how often complex emergency surgical cases are treated by general
      surgeons working outside their own elective subspecialty. METHOD: In a district
      general hospital in the south of the UK serving a population of 550 000 where
      there is almost complete subspecialization within general surgery, 1554 patients
      having emergency general surgical operations were studied in a one-year review.
      The time an operation occurred, the seniority of the operating surgeon, the
      subspecialty interest of the consultant responsible for the case compared with
      the specialist nature of the operation was determined. RESULTS: Of 1554 patients
      having emergency general surgical operations, 23% (352/1554) were of a high
      category of complexity. Ninety were vascular procedures and were dealt with by
      specialist vascular surgeons on a separate rota. Of the remaining 262 operations,
      78 (30%) did not match the subspecialty of the consultant surgeon responsible for
      their care; 56 (72%) of these occurred out of hours of which 14 (18%) had a
      consultant surgeon present and scrubbed in the theatre; one per month of the
      study. Seventy-three percent (57/78) of these were complex colorectal operations.
      CONCLUSION: The mismatch between the subspecialist elective interests of the
      consultant general surgeon and out of hours specialist major surgery needing
      consultant involvement occurred infrequently, and was mainly due to major lower
      gastrointestinal cases managed by upper gastrointestinal and breast surgeons.
      This has important implications for the future training of general surgeons and
      the provision of an emergency nonvascular general surgical service.

PMID- 16630230
TI  - Timing of restorative proctectomy following subtotal colectomy in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: There is no general consensus regarding the timing of restorative
      proctocolectomy (RPC) in patients who have undergone subtotal colectomy with end
      ileostomy (STC). The aim of this study was to determine the impact of timing of
      RPC in patients who have undergone subtotal colectomy and end ileostomy for
      inflammatory bowel disease (IBD). METHODS: A retrospective medical record review
      of patients who had undergone RPC after STC was undertaken. Patients were divided
      into 3 groups according to timing of the completion proctectomy: <or= 3 months, 4
      7 months and > 7 months. RESULTS: From 1990 to 2000, 91 patients had undergone
      RPC after STC for IBD. There were no statistically significant differences among
      the three groups relative to mean age, gender, final diagnosis, duration of
      disease, body mass index, comorbidity, extraintestinal manifestations, use of
      immunuosuppressives, or operative time. The number of intra-operative
      complications were significantly higher in the <or= 3 month group compared to the
      other groups. There was no significant difference in the overall incidence of
      postoperative complications among the 3 groups. Postoperative fistulas were
      significantly more common after RPC in Groups 1 and 2 as compared to Group 3.
      CONCLUSION: Restorative proctocolectomy performed within 3 months after the
      initial subtotal colectomy was associated with a significant increase in the
      incidence of intra-operative complications. Although this increase was not
      statistically significant, there was a significantly higher incidence of fistula
      formation when RPC was undertaken at up to 7 months after the subtotal colectomy
      for IBD. Thus, if possible, early RPC after subtotal colectomy should be
      discouraged.

PMID- 16630231
TI  - Effects of radiotherapy on different histopathological types of rectal carcinoma.
AB  - BACKGROUND: Down staging by pre-operative chemoradiotherapy is currently
      considered part of the standard therapeutic approach to rectal carcinoma. The aim
      of this study was to assess the response to chemoradiotherapy of different
      histopathological types of rectal carcinoma with emphasis on the mucinous
      variant. METHOD: Between 1997 and 2002, 71 patients who received pre-operative
      chemoradiotherapy followed by surgery for rectal carcinoma were enrolled in the
      study. Staging of the rectal carcinoma was performed according to transrectal
      ultrasound findings (TN score) prior to the chemoradiotherapy. The
      chemoradiotherapy was followed by radical resection with mesorectal excision. All
      surgical specimens were examined by a single pathologist (MB). Pathological TN
      staging was assessed and tumour regression was graded according to a standard
      method (TRG1, complete response - TRG5 no response). Tumours were classified as
      mucinous or nonmucinous according to pre- and post-operative biopsy and specimen
      histopathological types. TN score change and TRG differences between groups were
      assessed. RESULTS: Tumour regression was seen after chemoradiotherapy in 94.4% of
      the patients, while in 5.6% of the patients no response was found. The change in
      TN score and TRG were correlated. Higher TRG was associated with a smaller
      decrease in TN staging. TRG was significantly lower in the nonmucinous compared
      to the mucinous group and the decrease in TN grade was significantly larger in
      the nonmucinous group. CONCLUSION: Mucinous carcinoma was associated with a lower
      response to pre-operative chemo-radiotherapy in this group of rectal carcinoma
      patients. Further studies are needed to determine its prognostic value.

PMID- 16630232
TI  - Straight to test: introduction of a city-wide protocol driven investigation of
      suspected colorectal cancer.
AB  - OBJECTIVE: To decrease waiting times for colorectal cancer diagnosis. METHODS:
      Following extensive negotiations on three sites, we replaced the standard
      referral route of GP to outpatient clinic with city-wide implementation of a
      protocol driven sequence based on the patient's declared symptoms, the initial
      consultation being replaced by the first test taking place within 31 days. No
      choice in test allocation was granted; difficult cases were adjudicated by named
      consultants. We used a 'dry run' to make sure that our planned changes would not
      overload our local capacity, leading to a pilot run involving 1/3 clinicians,
      followed by a full cross-city implementation over two months. RESULTS: In 2001,
      before the pilot only 116/188 (62%) of our colorectal cancers who were referred
      either under the 2-week-wait arrangements or on a 'soon' basis were diagnosed
      within 31 days of referral. Our 'dry run' established that we did have the
      capacity to service our planned sequence of tests. In the pilot, all colorectal
      cancers were diagnosed within 31 days of referral, and 95% of all diagnoses (no
      abnormality or benign disease) were reached within 31 days of referral. After
      full implementation 19/19 (100%) of our cancers coming through our protocol
      system were diagnosed within 31 days and 95% of patients with benign disease.
      CONCLUSION: Follow-up audit of our system one and two years later shows that we
      now diagnose approximately 80% of our colorectal cancers who are referred under
      the 2 week wait or as 'soon' referrals within 31 days. We have successfully
      redesigned our service, at minimal expense, in a way, which should enable us to
      meet the government targets in the National Cancer Plan.

PMID- 16630233
TI  - The adenoma carcinoma sequence: an indoctrinated model for tumorigenesis, but is
      it always a clinical reality?
AB  - OBJECTIVE: Evidence exists to support alternative pathways to the adenoma
      carcinoma sequence. Some mutations in key onco-suppressor genes relate to the
      anatomical site of the tumour. This link is typified by microsatellite
      instability and proximal neoplasia. However, rectal tumours are rarely considered
      separately. We hypothesized that tumour behaviour in the rectum may differ in
      terms of pathogenesis and malignant propensity. Therefore, we aimed to look for
      an association between the histopathological features of adenomas and their
      anatomical location as compared with the distribution of cancers. METHODS: A
      single centre prospective study was undertaken over a four-year period. Patients
      referred to a colorectal assessment clinic with bowel symptoms underwent a
      minimum investigation of flexible sigmiodoscopy. Neoplastic lesions were either
      biopsied or removed after noting distance from the anal margin. Adenomas,
      differentiated by size, villous architecture and degree of dysplasia were
      compared to both early and advanced carcinomas. RESULTS: Of 4089 patients, polyps
      were identified in 8.0% and cancer in 4.2%. There was a clear difference between
      the distribution of cancer and adenomas > 1 cm, P < 0.001. All degrees of
      dysplasia in large adenomas were more prevalent in the sigmoid colon as compared
      to cancer, P < 0.001. Seventy-five percent of high risk diminutive adenomas were
      rectal in origin. CONCLUSION: Our data provides indirect evidence to support the
      concept that a significant proportion of rectal cancers may arise via an
      alternative pathway to the Vogelstein model. Polyp behaviour along with malignant
      propensity may actually be site dependent, with rectal polyps harbouring a more
      aggressive phenotype.

PMID- 16630234
TI  - Categorization of major and minor complications in the treatment of patients with
      resectable rectal cancer using short-term pre-operative radiotherapy and total
      mesorectal excision: a Delphi round.
AB  - BACKGROUND: To properly balance the benefit (reduction of local recurrence) of
      short-term pre-operative radiotherapy for resectable rectal cancer against its
      harm (complications), a consensus concerning the severity of complications is
      required. The aim of this study was to reach consensus regarding major and minor
      complications after short-term radiotherapy followed by total mesorectal excision
      in the treatment of rectal carcinoma, using the Delphi technique. METHODS: A
      Delphi round was performed in cooperation with 21 colo-rectal surgeons from the
      Netherlands, United Kingdom and Sweden. The key-question was: 'Which of the
      predefined complications, caused or substantially aggravated by radiotherapy, are
      so important (major) that they might lead to the decision to abandon short-term
      pre-operative radiotherapy (5 x 5Gy) when treating patients with resectable
      rectal cancer (T1-3N0-2M0)?' RESULTS: After three rounds, consensus was reached
      for 37 (68%) of 54 complications of which 13 were considered major and 24
      considered minor. The following complications were considered to be major:
      mortality, anastomotic leakage managed by relaparotomy, anastomotic leakage
      resulting in persisting fistula, postoperative haemorrhage managed by
      relaparotomy, intra-abdominal abscess without healing tendency, sepsis, pulmonary
      embolism, myocardial infarction, compartment syndrome of the lower legs, long
      term incontinence for solid stool, long-term problems with voiding, pelvic
      fracture with persisting pain, and neuropathy with persisting pain (legs). Three
      of 17 complications without consensus showed a tendency to be considered as
      major: perineal wound dehiscence managed by surgical treatment, small bowel
      obstruction leading to relaparotomy and long-term incontinence for liquid stool.
      CONCLUSION: The 13 major and three 'accepted as major' complications can be used
      to properly balance the benefit and harm of short-term pre-operative radiotherapy
      in resectable rectal cancer. This may eventually lead to improved treatment
      strategies for these patients.

PMID- 16630235
TI  - Posterior pelvic exenteration for primary rectal cancer.
AB  - BACKGROUND: Indications for and the prognosis of posterior pelvic exenteration
      (PPE) in rectal cancer patients are not clearly defined. The aim of this study
      was to analyse the indications, complications and long-term results of PPE in
      patients with primary rectal cancer. METHODS: A retrospective review included
      patient demographics, tumour and treatment variables, and morbidity, recurrence,
      and survival statistics. These results were compared with a group of female
      patients who underwent standard resection for primary rectal cancer in the same
      period (non PPE group). RESULTS: The series included 30 women with an average age
      of 56.7 years (range 22-78). Tumour location was recorded in three cases in the
      upper rectum, 13 cases in the medium rectum and 14 cases in the lower rectum. A
      sphincter-preserving procedure was performed in 70% of the patients. Mean
      operative time was 4.2 h (range 2-7.5 h). Overall major morbidity rate in this
      series was 50% and mean hospital stay was 19.7 days (range 9-60 days). There was
      no hospital mortality. Pathological reports showed direct invasion of uterus,
      vagina or rectovaginal septum in 19 cases, involvement of perirectal tissue in 25
      cases and positive lymph nodes in 18 cases. Comparison between PPE and non PPE
      groups showed no differences in mean tumour diameter, histological grade and
      tumour stage, but patients in the first group were younger. Although low tumours
      were seen more frequently in the PPE group (P = 0.003), the rate of sphincter
      preserving procedure was comparable in both groups. Operative time was longer (P
      = 0.04) and morbidity was higher (P = 0.0058) in the PPE group. Local recurrence
      with or without distant metastases for the whole series was 30%. Five-year
      survival rate for patients who underwent curative resections (TNM I-III) was 48%
      in the PPE group vs 62% in the non PPE group (P = 0.09). CONCLUSIONS: In the
      present series, PPE prolonged operative time, increased postoperative
      complications and showed a trend toward poor prognosis in recurrence and
      survival. However, PPE offers the only hope for cure to patients with a primary
      rectal cancer that is adherent or invades reproductive organs.

PMID- 16630236
TI  - Cleft closure for the treatment of unhealed perineal sinus.
AB  - OBJECTIVE: Despite improvements in surgical practice, persistent perineal wound
      sinus is still a common complication after proctectomy. This study presents the
      success of a modified cleft closure technique in dealing with this problem.
      METHODS: From May 1997 patients with a persistent perineal sinus after surgery
      underwent a cleft closure - similar to that performed for patients with pilonidal
      sinus disease. RESULTS: Eight patients (6 male, 2 female) with an average age of
      52 years underwent a cleft closure for a persistent perineal sinus after surgery.
      Four patients had undergone a proctocolectomy (ulcerative colitis), 2 an
      abdominoperineal excision of the rectum (adenocarcinoma) and 2 a proctectomy (1
      Crohn's disease, 1 complication of diverticular disease). Symptoms had been
      present for an average of 41 months (range 5-152 months) and 3 patients had
      undergone other procedures attempted previously to deal with the problem. The
      first three patients had the procedure as an inpatient with an average stay of
      4.7 days. The next 5 patients had the procedure as a day case (2 local
      anaesthetic, 3 general anaesthetic). Two patients developed a postoperative wound
      infection and all but one wound had healed completely by 8 weeks. In this patient
      the procedure was repeated to achieve healing. There was no other associated
      morbidity and no postoperative deaths. There have been no recurrences to date.
      CONCLUSION: Modified cleft closure for persistent perineal sinus is a simple
      procedure with low morbidity that can be performed under local anaesthetic in the
      day surgery unit.

PMID- 16630237
TI  - Sacral neuromodulation; does it affect colonic transit time in patients with
      faecal incontinence?
AB  - OBJECTIVE: Sacral neuromodulation (SNM) has been a successful treatment in
      urinary voiding disorders for years. A concomitant effect on bowel function was
      observed leading to the treatment of faecal incontinence with SNM. In this study
      we describe the effect of SNM on bowel frequency and (segmental) colonic transit
      time. PATIENTS AND METHODS: Fourteen patients with faecal incontinence who
      qualified for permanent SNM underwent a colon transit study before and one month
      after permanent implant. Patients completed a three-week bowel habits diary
      before and during stimulation. RESULTS: Median incontinence episodes and days per
      week before SNM were, 8.7 and 4.2, respectively, and both decreased significantly
      to 0.67 (P = 0001) and 0.5 (P = 0001) during trial screening and to 0.33 (P =
      0001) and 0.33 (P = 0001) after permanent implant. The median number of bowel
      movements per week decreased from 14.7 (6.7-41.7) to 10.0 (3.7-22.7)(P = 0005)
      during trial screening and to 10.0 (6.0-24.3)(P = 0008) during permanent
      stimulation. Resting and squeeze pressures did not change significantly during
      stimulation. Segmental colonic transit time before and during stimulation for
      right colon, left colon and recto sigmoid were, respectively, 6 (0-25) vs 5 (0
      16) hours, 2 (0-29) vs 4 (0-45) hours and 7 (28) vs 8 (0-23) hours. No
      significant changes were found in both segmental and total colonic transit time;
      17 (1-65) vs 25 (0-67) hours. CONCLUSION: SNM in patients with fecal incontinence
      led to a significant decrease of bowel movements however (segmental) colonic
      transit time was not influenced.

PMID- 16630238
TI  - Metachronous colorectal cancer.
AB  - OBJECTIVE: Although the diagnosis of metachronous colorectal cancer have
      increased, due primarily to improvements in diagnostic modalities, the potential
      risk factors for these tumours are not well known. We compared the
      characteristics of patients with metachronous and sporadic primary colorectal
      cancer to determine risk factors for its occurrence. PATIENTS AND METHODS: We
      reviewed the records of 5447 patients with colorectal cancer, who had been
      treated at Asan Medical Centre between July 1989 and January 2004. A metachronous
      cancer was defined as a secondary colorectal cancer occurring more than 6 months
      after the index cancer. RESULTS: Metachronous colorectal cancer occurred in 39
      (0.7%) patients. Their average age was 53 years, somewhat younger than the
      average age of sporadic colorectal cancer patients (58 years). In patients with
      metachronous cancer, the cancer was more likely to be located in the right colon
      (P < 0.03), and the incidence of synchronous polyps or cancer was significantly
      higher (P < 0.001). The relative distributions of histological grades and
      clinicopathological characteristics were similar in index and metachronous
      cancers. Metachronous cancers were diagnosed more frequently at an early stage.
      The time interval between index and metachronous cancer ranged from 6 to 215
      months (mean 39 months), with 13 (33.3%) patients diagnosed with metachronous
      cancer after 5 years. CONCLUSION: We found that in patients aged < 50 years,
      existence of synchronous polyps or cancer influence on the development of
      metachronous colorectal cancer. Regular follow-up is necessary for early
      detection, even after 5 years, for these patients.

PMID- 16630239
TI  - The Snug Seton: short and medium term results of slow fistulotomy for idiopathic
      anal fistulae.
AB  - OBJECTIVE: To assess the short and intermediate outcomes of a modification of the
      traditional cutting seton technique, using a 'snug' silastic seton, to treat
      idiopathic anal fistulae. PATIENTS AND METHODS: Between August 1997 and December
      2002, 35 patients with idiopathic fistulae (4 female; age 26-76 years) underwent
      insertion of a 'snugly' tied 1 mm silastic seton (silicone nerve vessel
      retractor, Medasil), as definitive treatment. Short-term assessment was performed
      by case note review. Patients were subsequently invited to participate in a
      medium-term review. RESULTS: Twenty-nine patients' notes (3 female) were
      available for short-term analysis. Fistulae were classified as intersphincteric
      (9) and transsphincteric (20). The seton spontaneously cut out in 15/29 (52%)
      after a median of 24 weeks. In 14 patients the seton enclosed residual tissue (<
      5 mm) required division as a day case procedure, at a median of 35 weeks. All
      fistulae healed but 10/29 (34%) patients (1 female; 8 transsphincteric)
      experienced minor incontinence. Sixteen patients participated in a medium-term
      review at a median of 42 months; 7 had experienced early continence disturbance.
      No patient suffered recurrence, but minor incontinence persisted in 4/16 (25%)
      patients (0 females; 3 transsphincteric). All patients were at least 'satisfied'
      with the outcome. CONCLUSION: In the short and medium term, the 'snug' seton is a
      safe and effective addition to the fistula surgeon's armamentarium.

PMID- 16630240
TI  - The use of intra-operative endo-anal ultrasound in perianal disease.
AB  - INTRODUCTION: Endoanal ultrasound (EAUS) has demonstrated high sensitivity and
      specificity for the structural imaging of anorectal pathology. This study
      prospectively assessed the impact of intra-operative EAUS on the surgical
      management of perianal disease. METHODS: EAUS was performed prior to and after
      examination under anaesthesia (EUA) in a consecutive series of patients with
      perianal disease. The impact of EAUS on the surgery performed was identified.
      RESULTS: Forty-three procedures have been performed in 38 patients (21 male, 17
      female; mean age 42.7 years, range 6-76 years) over a three year period.
      Pathologies encountered were fistula-in-ano (42%), fissure-in-ano (26%),
      complicated perianal sepsis (16%) and carcinoma (5%). No specific abnormality was
      identified in 5 symptomatic patients (12%). Four patients with fissures had
      undergone previous sphincterotomy. In 22 cases (51.2%) the EAUS findings affected
      the surgical management (extent of muscle above a fistula 9 cases, extent of
      sphincterotomy 7 cases, site of sepsis identified 2 cases, exclusion of sepsis 2
      cases, assessment of cancer resectability 1 case, biopsy of intersphincteric
      lesion 1 case). CONCLUSION: Intra-operative EAUS accurately identifies perianal
      disease and influences the surgical procedure performed. While not essential, it
      is a useful adjunct especially in recurrent perianal sepsis, undiagnosed
      anorectal pain and anal fissure.

PMID- 16630241
TI  - Endoluminal formalin application for haemorrhagic radiation proctitis.
AB  - BACKGROUND: Radiation proctitis is a common complication following radiation
      therapy for pelvic malignancies. This is associated with significant morbidity
      which adversely affects the quality of life. Local application of formalin has
      been used effectively in the treatment of radiation proctitis. METHODOLOGY:
      Thirty patients with haemorrhagic radiation proctitis who underwent endoluminal
      application of 4% formalin between January 1998 to October 2002 were followed up
      prospectively to assess the efficacy of the treatment. RESULTS: The follow up
      ranged from 5 to 36 months (mean 18.1 months). Nineteen (63.3%) patients had
      complete response to formalin application while 7 (23.3%) patients had partial
      response. There were 4 (13.3%) failures. No procedure related complication was
      observed. CONCLUSION: Local application of formalin is a simple, safe,
      inexpensive and fairly effective outpatient treatment modality for chronic
      radiation proctitis.

PMID- 16630242
TI  - Diagnosis and management of colovesical fistulae; six-year experience of 90
      consecutive cases.
AB  - INTRODUCTION: Colovesical fistulae are well-recognized but relatively uncommon
      presentation to colorectal surgery. As a result, few centres have sufficient
      experience in the investigation and surgical treatment of colovesical fistulae to
      develop clear protocols in its management. METHODS: This study examines the
      diagnostic and treatment pathways of 90 consecutive patients with colovesical
      fistulae presenting to a single surgeon, over a six-year period. Using the
      findings from this study and previously published data, the authors suggest
      tentative guidelines for the diagnosis and management of such patients. RESULTS:
      Pneumaturia and faecaluria were present in 90.1% of all cases. The diagnosis of
      colovesical fistula is predominately a clinical one, however, cystoscopy was the
      most accurate test to detect fistulae (46.2%) followed by barium enema (20.1%).
      Barium enema was the most sensitive test to detect stricture formation (70.6%).
      Colonic endoscopy was the most reliable means of excluding a colonic malignancy.
      The most common pathology was diverticular disease (72.2%), colonic carcinoma
      (15.3%) and Crohn's disease (9.7%). Left sided colonic resections were undertaken
      in 73.6% of patients, right hemicolectomy in 4.2% and defunctioning loop
      colostomies in 18.5%. Of the left sided resections, primary anastomosis was
      achieved in 92% of cases (n = 48) with one postoperative leak and no mortality.
      DISCUSSION: Resection and primary anastomosis should be the treatment of choice
      for colovesical fistulae, with an acceptable risk of anastomotic leak and
      mortality. Barium enema, colonic endoscopy and CT should be routine in the
      investigation of colovesical fistulae.

PMID- 16630243
TI  - Double-barrelled wet colostomy with simultaneous urinary and faecal diversion:
      results in 9 patients and review of the literature.
AB  - OBJECTIVE: Double-barrelled wet colostomy is a urinary diversion technique
      indicated when a concurrent faecal diversion is needed. It is a simple procedure,
      technically easy to accomplish and well received by patients. The purpose of this
      study is to report the results of double-barrelled wet colostomy, with emphasis
      on operating technique, morbidity, functional results and a review of the
      literature on the subject. METHODS: The medical records of 9 consecutive
      patients, between January 2001 and May 2005, who underwent surgical extended
      resections with double-barrelled wet colostomy for a malignant central pelvic
      mass, were reviewed retrospectively. The patients were asked to respond to a
      questionnaire assessing quality of life. The questionnaire used was the QLQ-C30
      version 3, proposed by the European Organization for Research and Treatment of
      Cancer (EORTC). RESULTS: This study presents results obtained from 9 patients,
      emphasizing morbidity and quality of life. One patient presented with
      pyelonephritis. We did not identify complications such as hydroelectrolytic
      disturbances, peristomal dermatitis or hydronephrosis. The patients who submitted
      to the procedure exhibited high levels of quality of life and found caring for
      the stomas straight forward. CONCLUSIONS: We conclude that double-barrelled wet
      colostomy is an excellent choice for patients who require concurrent urinary and
      faecal diversion, one that does not present technical difficulties and does not
      require a prolonged operating time. It avoids the complications frequently
      present in standard wet colostomy and does not rule out making a continent
      urinary reservoir later, in patients that meet healing criteria.

PMID- 16630244
TI  - Novel delivery of botulinum toxin for the treatment of anal fissures.
AB  - OBJECTIVE: Botulinum toxin A (Botox) has been used as a local treatment for anal
      fissure since 1994. It effects a reversible chemical sphincterotomy without the
      need for patient compliance. This study examines the feasibility of injecting the
      treatment using a needle-less system. PATIENTS AND METHODS: The optimal angle for
      injection was determined in a preclinical study using fresh porcine specimens.
      Ten patients with chronic anal fissures were then injected with 20 units Botox at
      the site of the fissure. They underwent assessment with a visual analogue pain
      scale, incontinence score and anal manometry pre-injection, at 48 h postinjection
      and at six and 12 weeks postinjection. They were also examined at the initial and
      final visits. RESULTS: The optimal angle for injection was 60 degrees . All 10
      patients (5 male; median age 40.5 years (range 26-68 years)) attended the 48 h
      follow up visit but only seven attended the six and 12 week visits. Six of seven
      patients healed their fissures. The remaining three were contacted by telephone
      at six months post injection and two of three remained asymptomatic without
      further treatment. In seven patients who underwent full follow up the median pain
      score pre-injection was 5.5 out of 10 (range 1-10) and this dropped to a median
      of 1 (range 0-6) at 12 weeks. The median drop in resting pressure was 47 cm H2O
      or 37% at six weeks. CONCLUSION: No needle injection of Botox is feasible with
      similar healing rates and reduction of resting pressure to conventional injection
      techniques.

PMID- 16630246
TI  - Risk factors for anastomotic leakage after anterior resection of the rectum.

PMID- 16630247
TI  - Glycolipid receptor depletion as an approach to specific antimicrobial therapy.
AB  - Mucosal pathogens recognize glycoconjugate receptors at the site of infection,
      and attachment is an essential first step in disease pathogenesis. Inhibition of
      attachment may prevent disease, and several approaches have been explored. This
      review discusses the prevention of bacterial attachment and disease by agents
      that modify the glycosylation of cell surface glycoconjugates. Glycosylation
      inhibitors were tested in the urinary tract infection model, where P-fimbriated
      Escherichia coli rely on glycosphingolipid receptors for attachment and tissue
      attack. N-butyldeoxynojirimycin blocked the expression of glucosylceramide
      derived glycosphingolipids and attachment was reduced. Bacterial persistence in
      the kidneys was impaired and the inflammatory response was abrogated. N
      butyldeoxynojirimycin was inactive against strains which failed to engage these
      receptors, including type 1 fimbriated or nonadhesive strains. In vivo attachment
      has been successfully prevented by soluble receptor analogues, but there is
      little clinical experience of such inhibitors. Large-scale synthesis of complex
      carbohydrates, which could be used as attachment inhibitors, remains a technical
      challenge. Antibodies to bacterial lectins involved in attachment may be
      efficient inhibitors, and fimbrial vaccines have been developed. Glycosylation
      inhibitors have been shown to be safe and efficient in patients with lipid
      storage disease and might therefore be tested in urinary tract infection. This
      approach differs from current therapies, including antibiotics, in that it
      targets the pathogens which recognize these receptors.

PMID- 16630248
TI  - Global analysis of iron assimilation and fur regulation in Yersinia pestis.
AB  - Using DNA microarray analysis, mRNA levels from wild-type Yersinia pestis cells
      treated with the iron chelator 2,2'-dipyridyl were compared with those
      supplemented with excessive iron, and subsequent to this, gene expression in the
      fur mutant was compared with that in the wild-type strain under iron rich
      conditions. The microarray analysis revealed many iron transport or storage
      systems that had been induced in response to the iron starvation, which is
      mediated by the Fur protein, using the iron as a co-repressor. The iron-Fur
      complex also affected some genes involved in various non-iron functions
      (ribonucleoside-diphosphate reductase, membrane proteins, electron transport and
      oxidative defense, etc.). The Fur protein still participated in the regulation of
      genes involved in broad cellular processes (virulence factors, pesticin activity,
      haemin storage and many proteins with unknown functions) that were not affected
      by iron depletion conditions. In addition to its classical negative regulatory
      activities, the Fur protein activates gene transcription. Using bioinformatics
      tools, we were able to predict the Y. pestis Fur box sequence that was clearly
      the over-presented motif in the promoter regions of members of the iron-Fur
      modulon.

PMID- 16630249
TI  - The bactericidal effect of TiO2 photocatalysis involves adsorption onto catalyst
      and the loss of membrane integrity.
AB  - The bactericidal effect of photocatalysis with TiO2 is well recognized, although
      its mode of action is still poorly characterized. It may involve oxidation, as
      illuminated TiO2 generates reactive oxygen species. Here we analyze the
      bactericidal effect of illuminated TiO2 in NaCl-KCl or sodium phosphate
      solutions. We found that adsorption of bacteria on the catalyst occurred
      immediately in NaCl-KCl solution, whereas it was delayed in the sodium phosphate
      solution. We also show that the rate of adsorption of cells onto TiO2 is
      positively correlated with its bactericidal effect. Importantly, adsorption was
      consistently associated with a reduction or loss of bacterial membrane integrity,
      as revealed by flow cytometry. Our work suggests that adsorption of cells onto
      aggregated TiO2, followed by loss of membrane integrity, is key to the
      bactericidal effect of photocatalysis.

PMID- 16630250
TI  - Comparison of bacterial flora and enzymatic activity in faeces of infants and
      calves.
AB  - Sixty-four breast-fed infants and 23 calves were investigated for bacteria and
      enzymatic activity in their faecal samples. The bacteria were measured using
      cultivation and fluorescence in situ hybridization. Enzymatic activity was also
      examined. Forty-seven (64%) infants and all the calves had high numbers of
      bifidobacteria (usually >9 log CFU g-1) in their faeces, but 17 infants (36%) did
      not have a detectable amount of the bacteria. Most of the bifidobacteria-negative
      infants had significant quantities of clostridia in their faecal flora. While the
      infants did not have significantly higher counts of bifidobacteria, the samples
      from calves contained significantly (P<0.05) more coliform bacteria and
      lactobacilli. There were also significant differences in their enzymatic
      activities. Bifidobacteria-positive samples had a greater alpha-glucosidase
      activity, while bifidobacteria-negative samples had a lower activity of alpha
      galactosidase, and calf samples had the highest beta-glucuronidase activity. A
      significant increase in bifidobacteria in calf faeces between days 3 and 7 was
      accompanied by a decrease in Escherichia coli. Our results show that the faecal
      flora of calves is similar to that of infants with regard to the occurrence of
      bifidobacteria as a dominant bacterial group.

PMID- 16630251
TI  - Evaluation of clonality in enterococci isolated in Brazil carrying Tn1546-like
      elements associated with vanA plasmids.
AB  - Fifty-one vancomycin-resistant enterococci samples isolated from different
      geographic regions in Brazil were studied. All the isolates harboured the vanA
      gene as demonstrated by PCR analysis, and in a majority of strains the gene was
      associated with a transferable plasmid of 70 kb. A single variant of the
      prototype Tn1546 associated with common transferable vanA-containing plasmids has
      spread among the enterococcal strains circulating in Brazil. The VanA element
      integrity in these enterococci strains and the different pulsed-field gel
      electrophoresis patterns suggest horizontal transmission of the vancomycin
      resistance transposon in Brazilian strains.

PMID- 16630252
TI  - Inheritance and state switching of genetic toggle switch in different culture
      growth phases.
AB  - Using the gene engineering methods, one can construct simple artificial gene
      networks with two stable functioning regimes (bistable genetic systems). Such
      genetic systems make it possible for cells with identical genotype to inherit two
      alternative phenotypes. The toggle switch is just one of the types of bistable
      genetic systems. In this work, we investigate the inheritance and switching of
      toggle switch functioning regimes in the cells at different culture growth
      phases. It is shown that during transition into the stationary growth phase the
      inheritance of stable states is disturbed and variations in the toggle-switching
      rate are more possible in different cells. Also, simultaneous expression of two
      genes of the system has been experimentally modelled. According to our results,
      the culture growth phase in this period determines later on the ratio between
      cell phenotypes in a population.

PMID- 16630253
TI  - Functional analysis of lymphostatin homologues in enterohaemorrhagic Escherichia
      coli.
AB  - Enteropathogenic Escherichia coli contain a large chromosomal gene (lifA) that
      encodes lymphostatin, a predicted 365 kDa protein that inhibits the mitogen
      activated proliferation of peripheral blood lymphocytes and lamina propria
      mononuclear cells and the synthesis of proinflammatory cytokines. Non-O157
      serotypes of enterohaemorrhagic E. coli (EHEC) contain a highly homologous gene,
      designated efa1 (EHEC factor for adherence), which influences adherence to
      epithelial cells in vitro and intestinal colonization in calves. Serotype O157:H7
      EHEC strains contain a truncated version of this gene (efa1') and a pO157-encoded
      homologue of lifA/efa1 (toxB). Here we report for the first time that efa1
      inhibits mitogen-activated proliferation of bovine peripheral blood lymphocytes
      by EHEC O103:H2, but that E. coli K-12 strains expressing the N-terminal and
      central portions of the protein lack activity. While a Shiga toxin-negative E.
      coli O157:H7 strain was shown to possess lymphostatin-like activity, deletion of
      efa1' or toxB, singly or in combination, failed to significantly relieve the
      inhibitory effect.

PMID- 16630254
TI  - Structure of euhalothece-362, a novel red-shifted mycosporine-like amino acid,
      from a halophilic cyanobacterium (Euhalothece sp.).
AB  - The unicellular cyanobacterium Euhalothece sp. strain LK-1, isolated from a
      gypsum crust on the bottom of a hypersaline saltern pond in Eilat, Israel,
      contains high concentrations of two mycosporine-like amino acids with maximum
      absorbance at 331 and 362 nm when grown at high light intensities. The 331 nm
      absorbing compound has previously been identified as mycosporine-2-glycine. Here,
      we confirm this identification and document the elucidation of the structure of
      the 362 nm absorbing compound ('euhalothece-362'), using liquid
      chromatography/mass spectrometry combined with other techniques, as a novel
      compound, 2-(E)-3-(E)-2,3-dihydroxyprop-1-enylimino-mycosporine-alanine.

PMID- 16630255
TI  - dye (arc) Mutants: insights into an unexplained phenotype and its suppression by
      the synthesis of poly (3-hydroxybutyrate) in Escherichia coli recombinants.
AB  - arcA codes for a central regulator in Escherichia coli that responds to redox
      conditions of growth. Mutations in this gene, originally named dye, confer
      sensitivity to toluidine blue and other redox dyes. However, the molecular basis
      for the dye-sensitive phenotype has not been elucidated. In this work, we show
      that toluidine blue redirects electrons to O2 and causes an increase in the
      generation of reactive O2 species (ROS). We also demonstrate that synthesis of
      poly (3-hydroxybutyrate) suppresses the Dye phenotype in E. coli recombinants, as
      the capacity to synthesize the polymer reduces sensitivity to toluidine blue, O2
      consumption and ROS production levels.

PMID- 16630256
TI  - Biochemical properties of a thermostable phytase from Neurospora crassa.
AB  - A gene (Ncphy) encoding a putative phytase in Neurospora crassa was cloned and
      expressed in Pichia pastoris, and the biochemical properties of the recombinant
      protein were examined in relation to the phytic acid hydrolysis in animal feed.
      The recombinant phytase (rNcPhy) hydrolyzed phytic acid with a specific activity
      of 125 U mg-1, Km of 228 micromol L-1, Vmax of 0.31 nmol (phosphate) s-1 mg-1, a
      temperature optimum of 60 degrees C and a pH optimum of 5.5 and a second pH
      optimum of 3.5. The enzyme displayed pH stability around pH 3.5-9.5 and showed
      satisfactory thermostability at 80 degrees C. The phytase from N. crassa has
      potential for improving animal feed processing at higher temperatures.

PMID- 16630257
TI  - Secretion of psychrophilic alpha-amylase deletion mutants in Pseudoalteromonas
      haloplanktis TAC125.
AB  - The nature and location of structural features responsible for the secretion of a
      cold-adapted alpha-amylase in the Antarctic marine bacterium Pseudoalteromonas
      haloplanktis TAC125 was studied by deletion mutagenesis of the wild-type enzyme
      and of chimerical proteins derived from the fusion of the alpha-amylase with a
      reporter enzyme. Domain C of the psychrophilic alpha-amylase contains secretion
      features involved in extracellular targeting.

PMID- 16630258
TI  - The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter
      baumannii.
AB  - ISAba1 was found in all widespread clones of Acinetobacter baumannii in the
      United Kingdom. All isolates studied had a blaOXA-51-like carbapenemase gene;
      some also had blaOXA-23-like and/or blaOXA-58-like. Among isolates with blaOXA-51
      like as sole carbapenemase gene, only those with ISAba1 adjacent to blaOXA-51
      like were carbapenem resistant. Minor differences in blaOXA-51-like sequence were
      observed in resistant and susceptible isolates. Isolates with blaOXA-23-like in
      addition were consistently resistant to carbapenems; in all of these ISAba1 lay
      upstream of blaOXA-23-like, but was not associated with blaOXA-51-like. These
      results suggest that ISAba1 is providing the promoter for blaOXA-51-like and,
      probably, for blaOXA-23-like.

PMID- 16630259
TI  - MSTF: a domain involved in bacterial metallopeptidases and surface proteins,
      mycobacteriophage tape-measure proteins and fungal proteins.
AB  - Here we report a novel domain, MSTF (domain involved in bacterial
      metallopeptidases, surface proteins and other proteins, also present in
      mycobacteriophage tape-measure proteins and fungal proteins), which is present in
      bacteria, phages and fungi. MSTF is about 67-94 amino acids in length with one
      HxDHxH motif and some highly conserved residues including His, Gly, Ala and Asp.
      Secondary structure prediction indicated that this domain contains two alpha
      helices and one beta-sheet. Identification of MSTF will provide an opportunity to
      develop new strategies to combat pathogenic microorganisms, especially
      Mycobacterium tuberculosis.

PMID- 16630260
TI  - Distinct DNA repair pathways involving RecA and nonhomologous end joining in
      Mycobacterium smegmatis.
AB  - Mycobacterium smegmatis was used to study the relationship between DNA repair
      processes involving RecA and nonhomologous end joining (NHEJ). The effect of gene
      deletions in recA and/or in two genes involved in NHEJ (ku and ligD) was tested
      on the ability of bacteria to join breaks in plasmids transformed into them and
      in their response to chemicals that damage DNA. The results provide in vivo
      evidence that only NHEJ is required for the repair of noncompatible DNA ends. By
      contrast, the response of mycobacteria to mitomycin C preferentially involved a
      RecA-dependent pathway.

PMID- 16630261
TI  - Aeromonas sobria hemolysin causes diarrhea by increasing secretion of HCO3-.
AB  - Aeromonas sobria hemolysin (ASH) is one of the major virulence factors produced
      by A. sobria, a causative agent of diarrhea in humans. We investigated the
      effects of ASH on anion transport in human colonic epithelial cells. ASH
      increased short circuit currents across the intestinal epithelia, which were
      suppressed by anion channel antagonists, such as carbonic anhydrase inhibitors,
      and by the removal of external HCO3-. Iliac fluid accumulation was also inhibited
      by carbonic anhydrase inhibitors. The results suggest that ASH activates HCO3-
      secretion, whose level correlates with the severity of diarrhea.

PMID- 16630262
TI  - Expression of a laccase cDNA from Trametes sp. AH28-2 in Pichia pastoris and
      mutagenesis of transformants by nitrogen ion implantation.
AB  - A laccase cDNA from Trametes sp. AH28-2 was expressed in Pichia pastoris, with
      the highest expression level of 4.0 mg L-1 (1360 U mg-1). The apparent Km (24.6
      microM) for ABTS (2,2'-azinobis [3-ethylbenzothia-zoline-6-sulfonic acid]) and
      the carbohydrate content of the recombinant laccase A (rLacA) are approximately
      identical to those of the native LacA (nLacA). However, the two enzymes differed
      in the pH optimum when both ABTS and guaiacol served as substrates. The optimum
      pH for enzyme stability is 5.5 for rLacA. Thermal stability was also
      investigated. The mutagenesis of rLacA utilizing low-energy nitrogen ion
      implantation resulted in the isolation of a yeast clone that produced 7.7 mg L-1
      (1085 U mg-1) of laccase, 92.5% more than the nonirradiated control (4.0 mg L-1).
      Compared with rLacA, the mutant LacA (mLacA) with five amino-acid residue changes
      in the coding sequence showed a slight change in its catalytic ability but
      superior thermal stability.

PMID- 16630263
TI  - Accumulation of deoxynivalenol and its 15-acetylated form is significantly
      modulated by oxidative stress in liquid cultures of Fusarium graminearum.
AB  - Liquid cultures of Fusarium graminearum were supplemented with H2O2 or other
      oxidative compounds. The accumulation kinetics of the resulting trichothecenes
      were monitored. At non-lethal concentrations, the H2O2 treatments modulated toxin
      accumulation, dependent on the method of supplementation. When H2O2 was added at
      the same time as the inoculation, higher levels of toxins accumulated 30 days
      later. Conversely, adding H2O2 2 or 7 days after inoculation had little effect.
      When H2O2 was added daily over the course of the culture, the accumulation of
      trichothecenes was rapidly and strongly enhanced. The fungus may adapt to
      oxidative stress when the first exposure to H2O2 occurs at the beginning of the
      culture course. The highest toxin levels were measured when the H2O2 was added
      daily. The importance of the first hours of culture was confirmed: pre-treating
      conidia with H2O2 does not affect their germination kinetics but leads to a
      reduction in the yield of trichothecenes 40 days later. The H2O2 regulation of
      this trichothecene accumulation may be specific, as paraquat, another pro-oxidant
      compound, inhibits their production. Since H2O2 is a major component of the
      oxidative burst occurring in pathogen/host interactions, these data support the
      theory that trichothecenes may act as virulence factors.

PMID- 16630264
TI  - Recognition of pore-forming colicin Y by its cognate immunity protein.
AB  - Construction of hybrid immunity genes between colicin U (cui) and Y (cyi)
      immunity genes and site-directed mutagenesis of cyi were used to identify amino
      acid residues of the colicin Y immunity protein (Cyi) involved in recognition of
      colicin Y. These amino-acid residues were localized close to the cytoplasmic site
      of the Cyi transmembrane helices T3 (S104, S107, F110, A112) and T4 (A159).
      Mutations in cui, which converted Cui sequence to Cyi sequence in positions 104,
      107, 110, 112 and 159, resulted in an immunity gene that also conferred (besides
      immunity to colicin U) a high degree of immunity to colicin Y.

PMID- 16630265
TI  - The ammonia channel protein AmtB from Escherichia coli is a polytopic membrane
      protein with a cleavable signal peptide.
AB  - The Escherichia coli ammonia channel protein, AmtB, is a homotrimeric polytopic
      inner membrane protein in which each subunit has 11 transmembrane helices. We
      have shown that the structural gene amtB encodes a preprotein with a signal
      peptide that is cleaved off to produce a topology with the N-terminus in the
      periplasm and the C-terminus in the cytoplasm. Deletion of the signal peptide
      coding region results in significantly lower levels of AmtB accumulation in the
      membrane but modification of the signal peptidase cleavage site, leading to
      aberrant cleavage, does not prevent trimer formation and does not inactivate the
      protein. The presence of a signal peptide is apparently not a conserved feature
      of all prokaryotic Amt proteins. Comparison of predicted AmtB sequences suggests
      that while Amt proteins in Gram-negative organisms utilize a signal peptide, the
      homologous proteins in Gram-positive organisms do not.

PMID- 16630266
TI  - The flavoprotein SoxF functions in chemotrophic thiosulfate oxidation of
      Paracoccus pantotrophus in vivo and in vitro.
AB  - Paracoccus pantotrophus strain GBsoxFDelta carries a deletion in the soxF gene
      that inactivates flavoprotein SoxF-sulfide dehydrogenase. This strain grew with
      thiosulfate slower than the wild type. GBsoxFDelta cells oxidized thiosulfate at
      a rate of 40% and hydrogen sulfide at a rate of 45% of the wild type.
      Complementation of GBsoxFDelta with plasmid pRIsoxF carrying the soxF gene
      increased these rates to 83% and 70%, respectively. However, GBsoxFDelta and
      GBsoxFDelta (pRIsoxF) oxidized thiosulfate and hydrogen sulfide to sulfate as
      evident from the yield of electrons. The thiosulfate oxidation rate of cell-free
      extracts of strain GBsoxFDelta was increased when supplemented with SoxF isolated
      from the wild type. However, SoxF did not affect the thiosulfate-oxidizing
      activity of the Sox enzyme system as reconstituted from the 'as-isolated' four
      Sox proteins. These data demonstrated that SoxF enhanced chemotrophic thiosulfate
      oxidation in vivo and acted on some component or condition present in whole cells
      and cell-free extracts but not present in the reconstituted system.

PMID- 16630267
TI  - Newly identified bacteriophages carrying the stx2g Shiga toxin gene isolated from
      Escherichia coli strains in polluted waters.
AB  - Shiga toxin-converting bacteriophages are the main vehicle involved in horizontal
      transmission of stx1 and stx2 genes, which has led to the current spread of stx
      genes among a high number of Escherichia coli serotypes and other enterobacteria.
      Several stx gene variants have been described, although some of the variants have
      never been isolated from inducible bacteriophages. In this study, two stx2g
      carrying bacteriophages induced from two different E. coli O2:H25 strains
      isolated from different wastewater samples were characterized. These
      bacteriophages when transduced into Shigella sonnei retained their ability to
      produce Stx2 protein. They had similar but not identical DNA restriction
      patterns, and similar host ranges. Electron microscopy studies showed that they
      had isometric capsids with short tails, which resembled phage 933W. However, DNA
      cross-hybridization studies showed that phage 933W was not closely related to
      stx2g bacteriophages. This first description of stx2g-carrying bacteriophages
      enlarges the list of stx-carrying bacteriophages involved in horizontal
      transmission of stx genes in the environment.

PMID- 16630268
TI  - Recurrent outbreaks of root mat in cucumber and tomato are associated with a
      monomorphic, cucumopine, Ri-plasmid harboured by various Alphaproteobacteria.
AB  - Recurrent outbreaks of root mat have occurred in the UK and France in cucumber
      and tomato. Root mat is caused by bacterial strains harbouring a Ri-plasmid
      (pRi). Fifteen root mat-associated (RMA) cucumopine pRi were analysed by PCR
      restriction fragment length polymorphism (RFLP) and Southern blotting. These pRi
      were harboured by Agrobacterium biovar 1 strains isolated during a 1970s outbreak
      of root mat in UK soil grown cucumber, and also by Agrobacterium biovar 1,
      Ochrobactrum, Rhizobium and Sinorhizobium isolated during outbreaks of root mat
      in cucumber and tomato grown hydroponically in the UK and France since 1993. PCR
      RFLP analysis of the T-DNA and virD2 regions showed sequence homology between all
      cucumopine pRi, indicating that these pRi are monomorphic, and thus this pRi
      remained in the UK without inducing symptoms for some 15 years between outbreaks
      in the 1970s and 1990s. Cucumopine pRi were also shown to possess the virE2
      substitute GALLS gene by Southern blotting. Two other pRi, harboured by
      Agrobacterium isolated from a recent root mat outbreak in one tomato crop, were
      also shown to possess the GALLS gene but were shown not to be cucumopine pRi by
      PCR-RFLP.

PMID- 16630269
TI  - First genetic characterization of a bacterial beta-phenylethylamine biosynthetic
      enzyme in Enterococcus faecium RM58.
AB  - Enterococcus faecium RM58 produces beta-phenylethylamine and tyramine. A gene
      from Ent. faecium RM58 coding for a 625 amino-acid residues protein that shows
      85% identity to Enterococcus faecalis tyrosine decarboxylase has been expressed
      in Escherichia coli, resulting in L-phenylalanine and L-tyrosine decarboxylase
      activities. Both activities were lost when a truncated protein lacking 84 amino
      acids at its C-terminus was expressed in E. coli. This study constitutes the
      first genetic characterization of a bacterial protein having L-phenylalanine
      decarboxylase activity and solves a long-standing question regarding the
      specificity of tyrosine decarboxylases in enterococci.

PMID- 16630270
TI  - Comparison of transcription of multiple genes at three developmental stages of
      the plant pathogen Sclerotinia sclerotiorum.
AB  - The ascomycete Sclerotinia sclerotiorum is a plant pathogen with a very broad
      host range. In order to identify and characterize genes involved in S.
      sclerotiorum infection of Brassica napus (canola), expressed sequence tags (ESTs)
      were examined from libraries prepared from three tissues: complex appressorium
      (infection cushions), mycelia grown on agar and lesions formed on leaves of B.
      napus. A high proportion of genes (68%) had not been previously reported for S.
      sclerotiorum in public gene or EST databases. The types of novel genes identified
      in the infection cushion library highlights the functional specificity of these
      structures and similarities to appressoria in other fungal pathogens.
      Quantitative real-time PCR was used to analyse tissue specificity and timing of
      transcription of genes with best matches to MAS3 (appressoria-associated protein
      from Magnaporthe grisea), cellobiohydrolase I, oxaloacetate acetylhydrolase,
      metallothionein, pisatin demethylase, and an unknown gene with orthologs in
      fungal pathogens but not in saprophytic fungi.

PMID- 16630272
TI  - Kluyveromyces lactis- a retrospective.

PMID- 16630273
TI  - The Kluyveromyces lactis repertoire of transcriptional regulators.
AB  - We have exploited the recently obtained complete genome sequence of Kluyveromyces
      lactis to compare the repertoire of transcriptional regulators between K. lactis
      and Saccharomyces cerevisiae. Looking for similarities with the S. cerevisiae
      proteins of this functional class, we observed a reduction in gene number, which
      is not randomly distributed among the different DNA-binding classes, the zinc
      binuclear cluster class (Zn(II)2Cys6), specific to ascomycetes, being one of the
      most affected. However, when one examines the number of proteins that, in the K.
      lactis genome, possess the different DNA-binding signatures, it is not reduced
      compared to S. cerevisiae. This indicates that transactivator proteins have
      strongly diverged between the two species and cannot be recognized any more,
      and/or that each genome has developed a specific set of regulators to adapt the
      cell to its specific niches. These two aspects are discussed on the basis of
      available data.

PMID- 16630274
TI  - The pheromone response pathway of Kluyveromyces lactis.
AB  - The mating pheromone response pathway in Saccharomyces cerevisiae is one of the
      best understood signalling pathways in eukaryotes. Comparison of this system with
      pathways in other fungal species has generated surprises and insights. Cloning
      and targetted disruption of genes encoding components of the pheromone response
      pathway has allowed the attribution of specific functions to these signal
      transduction components. In this review we describe current knowledge of the
      Kluyveromyces lactis mating system, and compare it with the well-understood S.
      cerevisiae pathway, emphasizing the similarities and differences in the
      heterotrimeric G protein activity. This mating pathway is controlled positively
      by both the Galpha and the Gbeta subunits of the heterotrimeric G protein.

PMID- 16630275
TI  - Evolution of gene families: the multidrug resistance transporter genes in five
      related yeast species.
AB  - The available genomic sequences of five closely related hemiascomycetous yeast
      species (Kluyveromyces lactis, Kluyveromyces waltii, Candida glabrata, Ashbya
      (Eremothecium) gossypii with Saccharomyces cerevisiae as a reference) were
      analysed to identify multidrug resistance (MDR) transport proteins belonging to
      the ATP-binding cassette (ABC) and major facilitator superfamilies (MFS),
      respectively. The phylogenetic trees clearly demonstrate that a similar set of
      gene (sub)families already existed in the common ancestor of all five fungal
      species studied. However, striking differences exist between the two
      superfamilies with respect to the evolution of the various subfamilies. Within
      the ABC superfamily all six half-size transporters with six transmembrane
      spanning domains (TMs) and most full-size transporters with 12 TMs have one and
      only one gene per genome. An exception is the PDR family, in which gene
      duplications and deletions have occurred independently in individual genomes.
      Among the MFS transporters, the DHA2 family (TC 2.A.1.3) is more variable between
      species than the DHA1 family (TC 2.A.1.2). Conserved gene order relationships
      allow to trace the evolution of most (sub)families, for which the Kluyveromyces
      lactis genome can serve as an optimal scaffold. Cross-species sequence alignment
      of orthologous upstream gene sequences led to the identification of conserved
      sequence motifs ("phylogenetic footprints"). Almost half of them match known
      sequence motifs for the MDR regulators described in S. cerevisiae. The biological
      significance of those and of the novel predicted motifs awaits to be confirmed
      experimentally.

PMID- 16630276
TI  - Mitochondrial chromosome structure: an insight from analysis of complete yeast
      genomes.
AB  - Recent progress in the analysis of protein components of the mitochondrial
      nucleoid and replisome of baker's yeast, Saccharomyces cerevisiae, opens a unique
      opportunity for understanding the molecular principles of mitochondrial
      inheritance. In this work we identified homologs of proteins involved in the
      mitochondrial DNA packaging and replication in the complete genome sequence of
      the petite-negative yeast Kluyveromyces lactis. Comparative analysis of their
      counterparts from phylogenetically diverse yeast species revealed conserved as
      well as diverged features of the organellar chromosome structure and its
      replication strategy. Moreover, it provides a basis for subsequent functional
      studies of the structure and dynamics of the mitochondrial nucleoids.

PMID- 16630277
TI  - Reoxidation of cytosolic NADPH in Kluyveromyces lactis.
AB  - Saccharomyces cerevisiae and Kluyveromyces lactis are considered to be the
      prototypes of two distinct metabolic models of facultatively-aerobic yeasts:
      Crabtree-positive/fermentative and Crabtree-negative/respiratory, respectively.
      Our group had previously proposed that one of the molecular keys supporting this
      difference lies in the mechanisms involved in the reoxidation of the NADPH
      produced as a consequence of the activity of the pentose phosphate pathway. It
      has been demonstrated that a significant part of this reoxidation is carried out
      in K. lactis by mitochondrial external alternative dehydrogenases which use
      NADPH, the enzymes of S. cerevisiae being NADH-specific. Moreover, the NADPH
      dependent pathways of response to oxidative stress appear as a feasible
      alternative that might co-exist with direct mitochondrial reoxidation.

PMID- 16630278
TI  - Heterologous protein production in the yeast Kluyveromyces lactis.
AB  - Kluyveromyces lactis is both scientifically and biotechnologically one of the
      most important non-Saccharomyces yeasts. Its biotechnological significance builds
      on its history of safe use in the food industry and its well-known ability to
      produce enzymes like lactase and bovine chymosin on an industrial scale. In this
      article, we review the various strains, genetic techniques and molecular tools
      currently available for the use of K. lactis as a host for protein expression.
      Additionally, we present data illustrating the recent use of proteomics studies
      to identify cellular bottlenecks that impede heterologous protein expression.

PMID- 16630279
TI  - Why does Kluyveromyces lactis not grow under anaerobic conditions? Comparison of
      essential anaerobic genes of Saccharomyces cerevisiae with the Kluyveromyces
      lactis genome.
AB  - Although some yeast species, e.g. Saccharomyces cerevisiae, can grow under
      anaerobic conditions, Kluyveromyces lactis cannot. In a systematic study, we have
      determined which S. cerevisiae genes are required for growth without oxygen. This
      has been done by using the yeast deletion library. Both aerobically essential and
      nonessential genes have been tested for their necessity for anaerobic growth.
      Upon comparison of the K. lactis genome with the genes found to be anaerobically
      important in S. cerevisiae, which yielded 20 genes that are missing in K. lactis,
      we hypothesize that lack of import of sterols might be one of the more important
      reasons that K. lactis cannot grow in the absence of oxygen.

PMID- 16630280
TI  - Mating-type locus control of killer toxins from Kluyveromyces lactis and Pichia
      acaciae.
AB  - Killer-toxin complexes produced by Kluyveromyces lactis and Pichia acaciae
      inhibit cell proliferation of Saccharomyces cerevisiae. Analysis of their actions
      in haploid MATalpha cells revealed that introduction of the opposite mating-type
      locus (MATa) significantly suppressed antizymosis. Together with resistance
      expressed by MATa/MATalpha diploids, the reciprocal action of MATa or MATalpha in
      haploids of opposite mating types suggests that these killer toxins may be
      subject to MAT locus control. Congruently, derepressing the silent mating-type
      loci, HMR and HML, by removing individual components of the histone deacetylase
      complex Sir1-4, either by transposon-tagging or by chemically inactivating the
      histone deacetylase catalytic subunit Sir2, yields toxin resistance. Consistent
      with MAT control of toxin action, killer-toxin-insensitive S. cerevisiae mutants
      (kti) become mating-compromised despite resisting the toxins' cell-cycle effects.
      Mating inhibition largely depends on the time point of toxin application to the
      mating mixtures and is less pronounced in Elongator mutants, whose resistance to
      the toxins' cell-cycle effects is the result of toxin-target process
      deficiencies. In striking contrast, non-Elongator mutants defective in early
      response events such as toxin import/activation hardly recover from toxin-induced
      mating inhibition. This study reveals a novel effect of yeast killer toxins on
      mating and sexual reproduction that is independent of their impact on cellular
      proliferation and cell-cycle progression.

PMID- 16630281
TI  - Heterologous complementation of the Klaac null mutation of Kluyveromyces lactis
      by the Saccharomyces cerevisiae AAC3 gene encoding the ADP/ATP carrier.
AB  - The KlAAC gene, encoding the ADP/ATP carrier, has been assumed to be a single
      gene in Kluyveromyces lactis, an aerobic, petite-negative yeast species. The
      Klaac null mutation, which causes a respiratory-deficient phenotype, was fully
      complemented by AAC2, the Saccharomyces cerevisiae major gene for the ADP/ATP
      carrier and also by AAC1, a gene that is poorly expressed in S. cerevisiae. In
      this study, we demonstrate that the Klaac null mutation is partially complemented
      by the ScAAC3 gene, encoding the hypoxic ADP/ATP carrier isoform, whose
      expression in S. cerevisiae is prevented by oxygen. Once introduced into K.
      lactis, the AAC3 gene was expressed both under aerobic and under partial
      anaerobic conditions but did not support the growth of K. lactis under strict
      anaerobic conditions.

PMID- 16630282
TI  - Characterization of a Kluyveromyces lactis mutant with altered regulation of
      mitochondrial alcohol dehydrogenases.
AB  - KlADH3 and KlADH4 are Kluyveromyces lactis genes encoding the two mitochondrial
      alcohol dehydrogenase activities located within mitochondria. In this yeast,
      ethanol induces the transcription of KlADH4 and, conversely, represses that of
      KlADH3. In this study, we describe the effects of the aar900 mutation on such
      regulation. This mutation, firstly isolated in a strain devoid of alcohol
      dehydrogenase genes except KlADH4, conferred to cells resistance to allyl alcohol
      because of the absence of the KlAdh4p activity. When the mutation was transferred
      by crosses to an isogenic strain containing all the alcohol dehydrogenase genes,
      we found that the KlADH3 gene was highly expressed even in the presence of
      ethanol. In addition, we observed that the absence of KlAdh4p resulted from a
      post-transcriptional control in that KlADH4 was transcriptionally induced by
      ethanol. We also found that KlPDC1, another ethanol-repressible gene, was not
      transcribed in the mutant in the presence of this carbon source, indicating that
      the escape of KlADH3 from ethanol repression was a peculiar feature of this gene.
      Genetic analysis showed a Mendelian segregation of the mutation that was mapped
      in a region of chromosome III close to the ade1 locus. Interestingly, the aar900
      mutants had a pleiotropic phenotype and showed increased resistance to monovalent
      cations and benomyl, suggesting that the mutation could also affect genes other
      than the alcohol dehydrogenase ones. Strains carrying the aar900 mutation could
      represent useful tools to unravel the peculiar regulation of KlADH3 and KlADH4 by
      ethanol.

PMID- 16630283
TI  - Structure of Kluyveromyces lactis subtelomeres: duplications and gene content.
AB  - We have constructed a map of the duplicated regions of Kluyveromyces lactis
      subtelomeres. Seven out of 12 subtelomeres contain an almost identical 9 kb long
      segment starting from the end. This segment is bordered by a long terminal repeat
      element. Two of the subtelomeres share sequence similarity that extends over a
      total of 20 kb. The other subtelomeres also contain duplicated regions of 1-6 kb.
      Nonduplicated regions contain unique genes and genes from paralog families. All
      duplicated segments are in the same orientation with respect to the telomere,
      probably as a result of genetic exchange. We map the only two copies of
      retrotransposons in the genome, in subtelomeres. Low-complexity gene sequences
      that encode threonine- and serine-rich peptides are associated with the
      subtelomeres of K. lactis, as in Saccharomyces cerevisiae. The ubiquity of these
      sequences in hemiascomycete genomes, and the propensity they have to encode
      proteins with extracellular localization, make these genes ideal candidates for
      fast evolving 'contingency' genes involved in the adaptation of a species to its
      environment.

PMID- 16630284
TI  - Screening for telomeric recombination in wild-type Kluyveromyces lactis.
AB  - Both subtelomeric and telomeric recombination events can be greatly enhanced in
      Kluyveromyces lactis mutants lacking telomerase and having abnormally short
      telomeres. In this study, we utilized cells containing a single telomere composed
      of mutant repeats carrying a phenotypically silent mutation to test whether the
      exchange of telomeric repeats was a frequent event in mitotic and meiotic wild
      type K. lactis cells. Amongst more than 100 subclones followed during multiple
      passages of mitotic growth, one instance of a terminal duplication extending into
      a subtelomeric sequence was observed, but no occurrences of intertelomeric
      recombination were found. This suggests that intertelomeric recombination is not
      an important contributor to telomere maintenance in normal K. lactis cells. Rare
      recombination events resulting in the replacement of a subtelomeric marker with a
      sequence from another chromosome end also led to the replacement of the telomeric
      repeat tract. This is consistent with these events being a result of break
      induced replication. Movement of a subtelomeric or telomeric sequence from one
      chromosome end to another was not observed in haploid cells derived from mating
      and sporulation. This suggests that the exchange of telomeric repeats is not a
      routine occurrence in K. lactis meiosis.

PMID- 16630285
TI  - The Kluyveromyces lactis alpha1,6-mannosyltransferase KlOch1p is required for
      cell-wall organization and proper functioning of the secretory pathway.
AB  - Mutants of Kluyveromyces lactis denominated vga (vanadate glycosylation affected)
      bear various combinations of glycosylation and cell-wall defects. The vga3
      mutation of K. lactis was mapped in the KlOCH1 gene, encoding the functional
      homologue of the Saccharomyces cerevisiaealpha1,6-mannosyltransferase.
      Quantitative analysis of cell-wall components indicated a noticeable increase of
      chitin and beta1,6-glucans and a severe decrease of mannoproteins in the mutant
      cells as compared with the wild-type counterparts. Fine-structure determination
      of the beta1,6-glucan polymer indicated that, in the vga3-1 strain, the beta1,6
      glucans are shorter and have more branches than in the wild-type strain. This
      suggests that cell-wall remodelling changes take place in K. lactis in the
      presence of glycosylation defects. Moreover, the vga3 cells showed a
      significantly improved capability of secreting heterologous proteins. Such a
      capability, accompanied by the highly reduced N-glycosylation, may be of
      biotechnological interest, especially when hyper-glycosylation of recombinant
      products must be avoided.

PMID- 16630287
TI  - On the natural course of oral lichen lesions in a Swedish population-based
      sample.
AB  - OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL)
      among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of
      327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in
      two Swedish municipalities, was followed through January 2002 via record linkages
      with nationwide and essentially complete registers. A sample of 80 drawn from the
      194 surviving subjects who still resided in the area in 1993-1995 was invited for
      interview and oral re-examination. RESULTS: At the end of follow-up, one case of
      oral cancer was detected, while 0.4 were expected. The overall mortality among
      subjects with OLL was not significantly different from that in the 15,817 OLL
      free subjects who participated in the initial population based survey in 1973
      1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with
      white OLLs in 1973-1974, and four (11%) had transformed into red types. In the
      corresponding group of 19 with red forms initially, five (26%) had become lesion
      free and four (21%) had switched to white types. Although the cohort size does
      not permit firm conclusions regarding oral cancer risk, the natural course over
      up to 30 years appears to be benign in the great majority.

PMID- 16630288
TI  - Lichenoid and granulomatous stomatitis: an entity or a non-specific inflammatory
      process?
AB  - BACKGROUND: The presence of lichenoid or granulomatous inflammation in an oral
      mucosal biopsy usually suggests a distinct range of diagnostic possibilities.
      However, the presence of both patterns of inflammation in the same biopsy is
      uncommon. METHODS: A clinico-pathological study of six patients. RESULTS: All the
      patients in this study presented with similar mucosal lesions of the upper lip.
      Microscopically the lesions were characterized by the presence of lichenoid
      inflammation with concomitant granulomatous inflammation. The lesions were
      persistent and refractory to treatment with steroid medications, but remained
      localized and did not appear to herald the onset of systemic inflammatory or
      neoplastic disease. CONCLUSION: We propose the designation 'lichenoid and
      granulomatous stomatitis' for the cases described in this study. The clinico
      pathological features of a subset of these cases suggest an unusual drug
      eruption.

PMID- 16630289
TI  - The immunohistology of CD40 in human oral epithelium in health and disease.
AB  - BACKGROUND: CD40 has a role in the regulation of immune responses, cell
      proliferation and migration, and apoptosis. Little is known of its distribution
      in oral mucosal pathology. METHODS: Oral keratinocyte lines were tested for CD40
      protein by Western blotting. Immunohistochemistry was used to stain paraffin
      sections of oral mucosa in health and in inflammatory, reactive, dysplastic and
      malignant disease. RESULTS: Western blotting confirmed the presence of CD40 in
      oral keratinocytes. CD40 was generally expressed by keratinocytes in the basal
      layer, with variable parabasal expression. Langerhans cells also stained
      positively. Expression was lost in nine of 33 (27%) epithelial dysplasias, seven
      of which were severe. Eighty-one percent of well, 69% of moderately and 50% of
      poorly differentiated oral squamous cell carcinomas (OSCC) expressed CD40.
      Overall, 45 of 65 (69%) OSCC were positive. The pattern of expression was
      unrelated to tumour differentiation. CONCLUSION: CD40 expression by basal and
      parabasal oral keratinocytes is physiological. Expression is lost in
      approximately one-third of oral epithelial dysplasias and OSCC. The significance
      of such loss remains unknown, but may be related to immunological or other
      abnormalities of keratinocyte homeostasis.

PMID- 16630290
TI  - Prognostic value of cyclin D1, p27, and p63 in oral leukoplakia.
AB  - BACKGROUND: Studies on the expression of genes regulating cell proliferation and
      apoptosis are essential to help better understand the severity and possible
      malignant transformation of oral leukoplakia. METHODS: The characteristics of
      cyclin D1, p27, and p63 were investigated in this microscopic study,
      complementing our previous results with Ki67, p53, and the apoptosis index.
      Clinical and histologic as well as immunohistochemical studies were carried out
      on oral leukoplakia of 18 patients. Homogenous, or non-homogenous (nodular or
      speckled) and erythroleukoplakia were determined clinically. Pathologic
      classification was performed according to the degree of dysplasia.
      Immunoperoxidase reaction for cyclin D1, p27, and p63 was carried out on the
      biopsy specimens and the positivity of the reactions was calculated for 1000
      epithelial cells. RESULTS: The expression of cyclin D1 increased in parallel with
      the severity of leukoplakia. The p27 index was 14-16% in homogenous and nodular
      leukoplakias but it was substantially lower to 1-2% in erythroleukoplakia. The
      p63 index was 10% in homogenous, 5% in nodular or speckled, but nearly 20% in
      erythroleukoplakia, on the average. CONCLUSION: These results suggest that the
      characteristic expression of cyclin D1, p27, and p63 in various forms of
      leukoplakia may be of prognostic value.

PMID- 16630291
TI  - Oligonucleotide microarray analysis of ameloblastoma compared with dentigerous
      cyst.
AB  - BACKGROUND: Ameloblastoma is a benign, but locally invasive tumor known for its
      high rate of recurrence. However, few comprehensive genetic studies have been
      conducted about its tumorigenesis. Our aim was to identify possible genes
      involved in the development and progression of ameloblastoma, using microarray
      analysis with dentigerous cyst as a control. METHODS: Total RNA was extracted
      from two fresh dentigerous cysts and ameloblastoma specimens. Following
      microarray analysis, semiquantitative reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry were performed on selected genes.
      RESULTS: Seventy-three genes were overexpressed and 49 were underexpressed. These
      genes were divided into categories according to function. The microarray results
      for 13 selected genes were verified with semiquantitative RT-PCR. CONCLUSIONS: We
      identified important genes related to the development and progression of
      ameloblastoma through a large-scale gene expression analysis. This study will
      stimulate further investigations on genes significant for early diagnosis and
      prognosis of ameloblastoma.

PMID- 16630292
TI  - Parotid carcinoma: expression of kit protein and epidermal growth factor
      receptor.
AB  - OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and
      epidermal growth factor receptor (EGFR) in parotid carcinomas in order to
      correlate the expression to histology and prognosis. Further we want to perform
      mutation analysis of KIT-positive adenoid cystic carcinomas. PATIENTS AND
      METHODS: Formalin-fixed paraffin-embedded sections from 73 patients with parotid
      gland carcinomas were used for the study. The sections were stained with both KIT
      and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas
      were examined for c-kit mutation in codon 816. RESULTS: Of all carcinomas 25%
      were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the
      adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic
      carcinomas had mutations in codon 816 of the c-kit gene. CONCLUSION: Neither KIT-
      nor EGFR-expression seem to harbour significant prognostic information. Adenoid
      cystic carcinomas express KIT, but no mutations in codon 816 of the c-kit gene
      were identified.

PMID- 16630293
TI  - The use of surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry to detect putative breast cancer markers in saliva: a feasibility
      study.
AB  - BACKGROUND: Technologies are now available enabling saliva to be used to diagnose
      disease, predict disease progression, and monitor therapeutic efficacy. This
      pilot study describes the use of surface-enhanced laser desorption/ionization
      time-of-flight mass spectrometry (SELDI) to detect putative breast cancer markers
      in saliva. METHODS: Salivary specimens were analyzed as either pooled cancer
      saliva specimens, or individual specimens from healthy women and women diagnosed
      with carcinoma of the breast. The specimens were applied to a variety of protein
      chip arrays, washed extensively to remove unbound analytes and analyzed on a
      SELDI mass spectrometer. RESULTS: The results of this initial study suggest that
      the WCX protein chip array prepared and washed at pH 3.5 yielded the most
      promising results. Additionally, the analyses revealed a number of proteins that
      were higher in intensity among the cancer subjects when compared with controls.
      These salivary proteins were present at the 18, 113, 170, 228 and 287 km/z ranges
      using SELDI analyses. CONCLUSIONS: The study suggests that saliva may be useful
      for high-throughput biomarker discovery.

PMID- 16630294
TI  - Reduced syndecan-1 expression is correlated with the histological grade of
      malignancy at the deep invasive front in oral squamous cell carcinoma.
AB  - BACKGROUND: Although many histopathological characteristics of oral squamous cell
      carcinoma (O-SCC) have been identified as prognostic factors, no factor is
      completely accurate and unequivocal. This study evaluated the association between
      the loss of syndecan-1 expression and the histological grade of malignancy at the
      deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the
      invasive tumor front of O-SCC was examined immunohistochemically using archived
      tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90
      years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24,
      11, and 11 cases classified as stages I-IV respectively. The correlation between
      the intensity of syndecan-1 immunostaining and the clinicopathological factors,
      especially the histological grade of malignancy at the deep invasive front
      (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29
      (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1
      staining respectively. There were significant differences between syndecan-1
      expression and prognosis, differentiation, and pattern of invasion at the deep
      invasive front. Moreover, the invasive front grade scores, based on the intensity
      of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points
      with strong, intermediate, and weak or negative intensity respectively; and the
      difference was significant (P < 0.0001). Patients with intermediate or strong
      intensity for syndecan-1 had significantly better prognoses than did those with
      negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that
      the reduced expression of syndecan-1 seems to be a useful marker of histological
      malignancy at the deep tumor invasive front and may be a useful prognostic factor
      in O-SCC.

PMID- 16630295
TI  - Personality analysis of patients complaining of sialorrhoea.
AB  - BACKGROUND: Sialorrhoea, the symptom of apparent excessive secretion of saliva is
      a relatively uncommon complaint. Some authors consider that in the absence of
      clinical findings, then these patients have a psychiatric disorder masquerading
      as a physical illness. However, there is little evidence in the literature to
      support this conclusion and a detailed psychological assessment of this
      population has not previously been reported. METHODS: In total, 18 patients and
      18 age- and sex-matched controls were studied. All had a history of a complaint
      of excess salivation in the absence of any oral mucosal or systemic abnormality.
      All patients completed an Eysenck Personality Questionnaire. RESULTS: There were
      no differences in the extroversion of psychoticism scores between the study and
      control group. However, the result showed significant increases in the
      neuroticism and Lie Scale score in the patient group. CONCLUSIONS: The overall
      results of this study indicate that the complaint of sialorrhoea in otherwise
      healthy individuals does not have an organic basis and suggest that sialorrhoea
      is associated with high levels of neuroticism and a tendency to dissimulate.

PMID- 16630296
TI  - Cleidocranial dysplasia with bilateral polycystic ovarian disease and Mullerian
      abnormality of the uterus: a case report.
AB  - We report an interesting case of cleidocranial dysplasia associated with an
      unusual finding of bilateral polycystic ovarian disease and bicornuate uterus
      with unicollis (Mullerian abnormality).

PMID- 16630297
TI  - Marginal zone B-cell lymphoma of minor salivary gland representing tumor-forming
      amyloidosis of the oral cavity. A case report.
AB  - We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma
      arising from the minor salivary gland of the oral cavity exhibiting tumor-forming
      amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4
      year history of a left soft palate mass. Despite multiple and multifocal
      recurrences including the lip, soft palate, tongue, oral base and vocal code and
      soft palate, the tumor remained localized in the upper aerodigestive tract, and
      the patient did not develop multiple myeloma during the course of disease.
      Histologically, the majority of the lesion was occupied by amyloid deposition.
      Only the periphery of the lesion contained numerous plasmacytoid cells, along
      with occasional centrocyte-like cells. In addition, lymphoepithelial lesion and
      follicular colonization were noted. The present case indicates that primary minor
      salivary gland MALT-type lymphoma appears to be the cause of tumor-forming
      amyloidosis of the upper aerodigestive tract including the larynx.

PMID- 16630298
TI  - White sponge naevus with minimal clinical and histological changes: report of
      three cases.
AB  - White sponge naevus (WSN) is a rare autosomal dominant disorder that
      predominantly affects non-cornified stratified squamous epithelia: oral mucosa,
      oesophagus, anogenital area. It has been shown to be related to keratin defects,
      because of mutations in the genes encoding mucosal-specific keratins K4 and K13.
      We illustrate three cases diagnosed as WSN, following the clinical and
      histological criteria, with unusual appearance. They presented with minimal
      clinical and histological changes that could be misleading in the diagnosis. The
      patients showed diffuse irregular plaques with a range of presentations from
      white to rose coloured mucosae involving the entire oral cavity. In one case the
      lesion was also present in the vaginal area. The histological findings included
      epithelial thickening, parakeratosis and extensive vacuolization of the
      suprabasal keratinocytes, confirming WSN diagnosis. Clinical presentation and
      histopathology of WSN are discussed in relation to the differential diagnosis of
      other oral leukokeratoses.

PMID- 16630299
TI  - A numeric code for identifying patterns of human tooth agenesis: a new approach.
AB  - Human tooth agenesis involves the absence of one or more teeth and often refers
      to a genetic or a developmental disorder. Identifying whether certain patterns of
      tooth agenesis are more prevalent than others may prove valuable for treatment
      planning, as well as for genetic research into its etiology and development. In
      the present article a method is described where unique values are assigned to
      patterns of tooth agenesis. Using the idea of binary arithmetic, the absence or
      presence of teeth are represented by 1 and 0, and translated into corresponding
      unique values, the Tooth Agenesis Code (TAC). This procedure has an advantage
      over existing methods in that it allows for easier data analysis. The method
      described in this article can advance genetic research towards the etiology of
      tooth agenesis, allows researchers to communicate unequivocally the phenotypes of
      their studied cases and it can be used in other areas of oral pathology that also
      require pattern recognition.

PMID- 16630300
TI  - World dental research production: an ISI database approach (1999-2003).
AB  - The objective of this study was to obtain a geographic world map of scientific
      production in dentistry by analysing published papers. Articles and reviews in
      the Dentistry, Oral Surgery & Medicine category published from 1999 to 2003 were
      accessed through the ISI database. The data were analyzed quantitatively (number
      of documents, number of researchers, productivity, interannual variation rate and
      relative specialization index), qualitatively (weighted impact factor, relative
      impact factor, citation rate per document and top 5 publications) and
      socioeconomically (number of documents per inhabitant and per dentist and in
      relation to the country's GDP). The USA, UK, Japan and Scandinavian countries
      were found to be the most productive countries (number of publications).
      Publications from Scandinavian countries were also of high quality as measured by
      Impact Factor and Citation Rate, while the UK had one of the highest productivity
      rates (number of documents per researcher).

PMID- 16630301
TI  - Symptoms of depression and anxiety in relation to dental health behavior and self
      perceived dental treatment need.
AB  - The purpose of this study was to investigate the dental health behavior and self
      perceived dental treatment need, in relation to depressive symptoms and symptoms
      of anxiety, among a general population drawn from a sample of 31-yr-old-men and
      women born in Northern Finland in 1966 (n = 8463). The dental health behavior
      included toothbrushing frequency and the frequency of dental check-ups.
      Depressive symptoms, as well as symptoms of anxiety, were determined on the basis
      of the Symptom Checklist-25 (SCL-25). The participants were also asked about
      their education and family income. Subjects with a high number of depressive
      symptoms had lower toothbrushing frequency as well as a lower frequency of dental
      visits than subjects with no or only a few depressive symptoms. Morover, the self
      perceived dental treatment need was more common among those with a high number of
      depressive symptoms. Symptoms of anxiety were significantly associated with lower
      toothbrushing frequency. The results support the view that there is an increased
      risk for impaired dental health among subjects with depressive symptoms or
      symptoms of anxiety.

PMID- 16630302
TI  - Oral Impacts on Daily Performance in Norwegian adults: the influence of age,
      number of missing teeth, and socio-demographic factors.
AB  - This study investigates the relationships among socio-demographic factors, dental
      status, and impaired oral health-related quality of life (OHRQoL) using a
      translation into Norwegian of the Oral Impacts on Daily Performance (OIDP)
      inventory. Data were collected as part of the Central Bureau of Statistics (CBS)
      OMNIBUS survey in Norway. The CBS drew a two-stage proportionate random sample,
      comprising 2,000 residents aged 16-79 yr, from the national population register.
      Information was available for 1,309 individuals (response rate 66.0%) who
      completed telephone interviews in November and December 2003. A total of 18.3%
      (95% confidence interval: 16.2-20.4) reported that an oral problem had affected
      at least one daily oral performance during the 6 months preceding the survey. The
      proportion of adults who confirmed impacts varied from 11.3% (eating) to 2.1%
      (social contact). Multiple logistic regression analysis revealed statistically
      significant disparities regarding respondents' age, residential area, dental
      attendance, and number of remaining teeth. The prevalence of OIDP in the
      Norwegian population was modest, but varied systematically with both socio
      demographic and oral health-related factors. The consistently declining OIDP with
      increasing age after controlling for dental status suggests age-related changes
      of participants' values and expectations.

PMID- 16630303
TI  - Dental and medical injections: prevalence of self-reported problems among 18-yr
      old subjects in Norway.
AB  - The aim of the present study was to evaluate the prevalence of self-reported
      problems (fear, pain, unpleasantness, fainting) of dental and medical injections,
      and the extent to which such problems may lead to avoidance of necessary
      treatment. The study included a representative sample (n = 1385) of 18-yr-old
      students attending high schools in the county of Hordaland, Norway. Data were
      collected by use of questionnaires completed in the classrooms. More problems
      were reported during dental than medical injections. About 17% and 15% of
      participants reported high fear during their last dental and medical injection,
      respectively. Fainting had been experienced by 2% during a dental injection and
      by 7% during a medical injection. Avoidance of treatment when an injection is
      needed was 6.7% for dental treatment and 5.2% for medical treatment. In multiple
      regression analyses, fear was the only explanatory factor for the avoidance of
      dental treatment. It is concluded that self-reported problems of injections are
      prevalent in this age group, particularly among girls, and that it may lead to
      the avoidance of necessary treatment in 5-7% of the adolescent population.

PMID- 16630304
TI  - Comparison of Clinpro Cario L-Pop estimates with CIA lactic acid estimates of the
      oral microflora.
AB  - Clinpro Cario L-Pop (CCLP) is a semiquantitive test claimed to determine the
      general potential for caries development and to monitor the individual caries
      risk. This test translates the capacity of the tongue microflora to produce
      lactic acid into a score of 1-9, indicating a low, medium or high risk for caries
      development. The aim of this randomized crossover, clinical trial was to evaluate
      the CCLP on its variation over time and its capacity to monitor the effect of
      three different oral hygiene procedures. The CCLP readings were compared with
      measurements of lactic acid in tongue biofilm and plaque samples by capillary ion
      electrophoresis (CIA). After four washout periods, the distribution of scores in
      the low-, medium-, and high-risk categories was 10%, 16%, and 74%, respectively.
      Out of 30 subjects, 11 scored consistently in the same category. The coefficients
      of variance of lactic acid concentrations were 31% for tongue samples and 25% for
      plaque samples. After using antimicrobial toothpaste and mouthwash, the number of
      high-risk scores was reduced to 33%; reduced acidogenicity was also found in
      tongue and plaque samples. We conclude that CCLP can be used to monitor and
      stimulate compliance to an antimicrobial oral hygiene protocol.

PMID- 16630305
TI  - Caries-induced changes in the expression of pulpal neuropeptide Y.
AB  - Recent evidence suggests that the sympathetic nervous system may have a role in
      modulating neurogenic inflammation and bone remodelling. Neuropeptide Y (NPY) is
      a well-characterized neuropeptide transmitter in the peripheral sympathetic
      nervous system. NPY is known to be present in human dental pulp; however,
      quantitative data on NPY levels in pulpal health and disease in an adult
      population remain to be determined. The aims of the current study were to assess,
      quantitatively, NPY levels by radioimmunoassay and confirm the distribution of
      NPY fibres by immunocytochemistry in carious and non-carious adult human pulp
      tissue. Our results suggest changes in the levels and distribution of NPY in
      human dental pulp during the caries process, with significantly higher levels of
      NPY in carious compared with non-carious adult human teeth. Within the carious
      samples studied, our finding, that NPY levels were significantly elevated in
      mild/moderate caries, concurs with the hypothesis that NPY could have a
      modulatory role in pulpal inflammation and in reparative dentine formation.

PMID- 16630306
TI  - Human pulp-derived cells immortalized with Simian Virus 40 T-antigen.
AB  - Primary cells in culture have a limited capacity to divide and soon reach a non
      proliferative state. This cellular senescence limits the investigation of cells
      derived from human pulp concerning cellular pathways, gene regulation, mechanisms
      of dentin formation, or responses to material exposure. To overcome this problem,
      primary human pulp-derived cells were established and transfected with a plasmid
      containing coding sequences of Simian Virus 40 (SV40) large T-antigen. This
      resulted in the establishment of several cell clones showing an extension of life
      span. Expression of T-antigen transcripts and protein was verified by reverse
      transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.
      Primary human pulp cells were cultured until senescence (i.e. up to passage 7)
      and transfected cells could be cultured to passage 18 after transfection, when a
      cellular crisis with massive cell death occurred. One clone escaped from crisis
      and has been maintained in culture for 55 wk. Experiments were performed to
      characterize transfected cells in comparison to primary cells. Cell morphology
      and proliferation were analyzed, and expression of cell-specific gene transcripts
      and proteins (including collagen types I and III, alkaline phosphatase, bone
      sialoprotein, osteocalcin, and dentin sialophosphoprotein and dentin matrix
      protein I) was detected by RT-PCR and immunohistochemistry. Transfection of human
      pulp-derived cells resulted in an immortalized cell line retaining many of the
      phenotypic characteristics observed in primary cells.

PMID- 16630307
TI  - Two-dimensional electrophoresis study of in vitro pellicle formation and dental
      caries susceptibility.
AB  - In the present study, a proteomic approach was applied to evaluate the influence
      of salivary protein composition on in vitro dental pellicle formation and its
      possible correlation with dental caries. Whole saliva, collected from caries-free
      and caries-susceptible subjects, was analyzed by two-dimensional electrophoresis,
      and protein spots were identified by mass spectrometry. Data analysis of salivary
      protein composition showed a statistically significant correlation between the
      quantity of acidic proline-rich proteins (PRPs), lipocalin, cystatin SN and
      cystatin S, and samples from the caries-free group of subjects [decayed, missing
      or filled teeth (DMFT) = 0]. Samples from subjects with a high DMFT index appear
      to be correlated with high levels of amylase, immunoglobulin A, and lactoferrin.
      In vitro pellicle-composition experiments showed the same correlations found for
      whole saliva. As cystatins are known physiological inhibitors of cathepsins, the
      higher quantities of lipocalin, and cystatins S and SN found in the samples from
      the caries-free subjects suggest that inhibition of proteolytic events on other
      salivary proteins may indirectly provide tooth protection. The correlation
      between higher levels of the phosphorylated acidic PRPs 1/2 with samples from the
      caries-free group also suggests a protective role for these proteins.

PMID- 16630308
TI  - Role of mitogen-activated protein kinase kinase in Porphyromonas gingivalis
      induced myocardial cell hypertrophy and apoptosis.
AB  - Secreted factors present in the medium following growth of the periodontal
      pathogen Porphyromonas gingivalis cause increased cardiomyocyte hypertrophy and
      apoptosis, whereas secreted factors from Actinobacillus actinomycetemcomitans and
      Prevotella intermedia have no such effects. The purpose of this study was to
      clarify the role of mitogen-activated protein kinase (MAPK)/extracellular
      regulated protein kinase (ERK) pathways in P. gingivalis medium-induced H9c2
      myocardial cell hypertrophy and apoptosis. Cellular morphology, DNA
      fragmentation, nuclear condensation, total mitogen-activated protein
      kinase/extracellular-regulated protein kinase-1 (ERK-1), total ERK-1 protein, and
      phosphorylated ERK-1 protein products in cultured H9c2 myocardial cells were
      measured by actin immunofluorescence, agarose gel electrophoresis, nuclear
      condensation, and western blotting following stimulation with P. gingivalis spent
      growth medium or pre-administration of U0126, a potent MEK-1/2 inhibitor.
      Components of P. gingivalis spent culture medium not only resulted in increased
      total MEK-1 and ERK-1 protein products, but also caused increased cellular size,
      DNA fragmentation, and nuclear condensation in H9c2 cells. These three
      parameters, and the phosphorylated ERK-1 protein products of H9c2 cells treated
      with P. gingivalis medium, were all significantly reduced after pre
      administration of U0126. The results suggest that P. gingivalis-secreted factors
      may initiate MEK/ERK signal pathways and lead to myocardial cell hypertrophy and
      apoptosis.

PMID- 16630309
TI  - Activation of gelatinolytic/collagenolytic activity in dentin by self-etching
      adhesives.
AB  - Mild acids are known to activate dentin matrix metalloproteinase (MMPs). All self
      etching dental adhesives are acidic (pH 1.5-2.7) and may activate dentin MMPs.
      The purpose of this study was to compare the ability of several all-in-one
      adhesives to activate gelatinolytic and collagenolytic activities in powdered
      mineralized dentin. Powdered dentin made from human teeth was mixed with all-in
      one adhesives (Clearfil Tri-S Bond, G-Bond, Adper Prompt L-Pop) or a self-etching
      primer (Clearfil SE Bond primer) for varying times and then the reaction was
      stopped by extracting the adhesives using acetone. Fresh untreated mineralized
      dentin powder had a gelatinolytic activity of 3.31 +/- 0.39 relative fluorescent
      units (RFU) per mg dry weight (24 h) that increased, over storage time, to 87.5
      RFU mg(-1) (24 h) after 6-8 wk. When fresh powder was treated with acidic Tri-S
      Bond, the gelatinolytic activity increased from 3.24 +/- 0.70 RFU mg(-1) to >
      112.5 RFU mg(-1) (24 h) after 20 min and then remained unchanged. Monomers with
      lower pH values produced less activity. There was a significant, direct
      correlation between gelatinolytic activity and pH, with Tri-S giving the highest
      activity. Coating dentin powder with Tri-S resin prevented fluorescent substrates
      from gaining access to the enzyme, even though it activated the enzyme. In
      conclusion, self-etch adhesives may activate latent MMP and increase the activity
      to near-maximum levels and contribute to the degradation of resin-dentin bonds
      over time.

PMID- 16630310
TI  - No effect of experimental occlusal interferences on pressure pain thresholds of
      the masseter and temporalis muscles in healthy women.
AB  - It has been suggested that occlusal interferences may lead to pain and tenderness
      of the masticatory muscles. Tender jaw muscles are more sensitive to pressure
      pain, as assessed by means of pressure algometry. We tested the effects of
      occlusal interferences on the pressure pain threshold of the jaw muscles by means
      of a double-blind randomized crossover experiment carried out on 11 young healthy
      females. Golden strips were glued either to an occlusal contact area (active
      interference) or to the vestibular surface of the same tooth (dummy interference)
      and left for 8 d each. Pressure pain thresholds of the masseter and anterior
      temporalis muscles were assessed under interference-free, dummy-interference and
      active-interference conditions. The results indicated that the application of an
      active occlusal interference, as used in this study, did not influence
      significantly the pressure pain thresholds of these muscles in healthy
      individuals.

PMID- 16630311
TI  - Structure of the periodontium in cathepsin C-deficient mice.
AB  - Papillon-Lefevre syndrome is characterized by increased susceptibility to early
      onset periodontitis and is caused by mutations in the cathepsin C gene. How
      deficiency of the enzyme relates to an increased periodontal infection risk is
      still not entirely clear. One possibility is that the deficiency leads to changes
      in the structure of the periodontal tissues as a result of which its barrier
      function to pathogens is compromised. We studied the structure of the
      periodontium in 9-month-old cathepsin C-deficient mice (cathepsin C(-/-)) and
      compared this with age-matched wild-type mice. Our observations showed that the
      overall structure of the gingiva, periodontal ligament, alveolar process, and
      cementum layer are normal in cathepsin C(-/-) mice, with one exception, namely
      that epithelial rests of Malassez in the periodontal ligament of the cathepsin C(
      /-) mice are slightly enlarged. In both experimental and control animals, we
      noted cyst formation in rests of Malassez. No signs of periodontal infection were
      observed. It is concluded that cathepsin C deficiency does not lead to major
      changes in the structure of the periodontium.

PMID- 16630312
TI  - Sweat testing for cystic fibrosis: How good is your laboratory?

PMID- 16630313
TI  - Evidence for a causal association between oral polio vaccine and transverse
      myelitis: A case history and review of the Literature.
AB  - A 6-month-old boy developed transverse myelitis 7 days after the receipt of oral
      polio vaccine (OPV). A paediatric neurologist confirmed the diagnosis when the
      boy was aged 9 years. The boy had received his first scheduled OPV at the age of
      4 months and had developed immunity to serotypes 1 and 2 but not to serotype 3. A
      poliovirus type 3 was isolated from stool and throat specimens collected from the
      boy in the first 2 days after symptom onset. This was shown, in a World Health
      Organization accredited laboratory, to be a vaccine strain by nucleic acid probe
      hybridiztion and enzyme-linked immunosorbent assay. The boy subsequently
      developed immunity to poliovirus serotype 3. It is accepted that poliovirus
      infection can present occasionally as transverse myelitis. This is estimated to
      occur in 1:125-1:800 cases. It is also accepted that OPV can cause vaccine
      associated paralytic polio with a frequency of approximately one case per 2.5
      million doses of OPV distributed. It seems feasible therefore that OPV could
      cause transverse myelitis with a frequency of 1 in 300 million to one in two
      billion doses distributed. In a 1993 report from the Institute of Medicine of the
      National Acadamies of the United States pertaining to vaccine safety, theoretical
      criteria were advanced for the establishment of a causal relationship between a
      vaccine and a clinical outcome. The clinical history and laboratory results in
      this case satisfy these criteria, providing plausible evidence for the causal
      link between OPV and transverse myelitis.

PMID- 16630314
TI  - Sweat testing for cystic fibrosis: A review of New Zealand laboratories.
AB  - BACKGROUND: Evolving diagnostic criteria for cystic fibrosis, broadening of the
      populations being tested and the need to interpret intermediate sweat test
      results have imposed a much greater need to standardize the collection and
      analysis of sweat. AIM: To identify variations in sweat testing in New Zealand
      laboratories and compare these with guidelines from the UK and the USA. METHODS:
      All laboratories in New Zealand offering sweat testing were identified and data
      collected from these laboratories by structured questionnaire. RESULTS: There
      were no New Zealand laboratories that conformed to either set of guidelines.
      Inconsistencies were observed in minimum sweat quantities, the nature of the
      iontophoresis solution, the sweat electrolytes analysed, quoted reference ranges
      and recommendations made as a consequence of the result. CONCLUSIONS: Conformity
      to the guidelines would help to minimize variation in sweat testing in New
      Zealand. Performance of a sufficient number of tests to maintain expertise is
      critical, but geographical constraints make patient travel to distant centres
      difficult in a small, scattered population. A possible solution, where numbers
      permit, may be the collection of sweat locally, with referral to a major
      laboratory for analysis. This is only possible with adequate training in
      collection and follow-up audit of the sweat testing procedure both in the
      collection and in the analytical phase.

PMID- 16630315
TI  - Measles immunity and immunisation status in Australian children 1 to 4 years of
      age.
AB  - AIM: Determine measles seropositivity and vaccine coverage in children aged 1 to
      4 years inclusive. Compare data in those who produced immunisation records and
      those who relied on parental recall. Establish variables associated with
      seropositivity. METHODS:  DESIGN: Population- and area-based, cluster sample of 1
      to 4-year-olds; households surveyed by trained interviewer. SETTING: Australia
      wide, excluding New South Wales. Questionnaires completed between February and
      April 1995. SUBJECTS: 2117 completed questionnaires were returned for children
      aged 1 to 4 years, 923 of whom provided a sufficient blood sample for analysis.
      RESULTS: Overall seropositivity was 86% for the 923 children tested and was
      strongly associated with previous immunisation (P < 0.001) and age (P < 0.001),
      but not with parental report of a previous measles diagnosis (P = 0.581). Eight
      hundred and forty-three (91%) reported previous measles immunisation, with 760
      (90%) of these testing seropositive. Four hundred and ninety-one (55%)
      parents/guardians produced immunisation records, while 400 (45%) relied on
      recall. Immunised children whose parents relied on recall were equally likely to
      be seropositive as children whose parents produced records. The 923 children
      tested were representative of the 2117 who completed questionnaires in all
      factors except age, where children below 2 years old were under represented (P <
      0.001). CONCLUSIONS: These data support the current second routine measles
      immunisation prior to school entry, and reinforce the need to promote the first
      routine dose to achieve measles elimination.

PMID- 16630316
TI  - Rapid sterilisation of cerebrospinal fluid in meningococcal meningitis:
      Implications for treatment duration.
AB  - AIM: The aim of this study was to determine the time and total cumulative dose of
      parenteral antibiotic, required to sterilize the cerebrospinal fluid (CSF) of
      children presenting with meningococcal meningitis (MM). METHODS: The study was a
      retrospective audit of children aged 0-14 years who presented between January
      1995 and December 1999 with MM. All cases had a delayed lumbar puncture (LP) at
      least 1 h after commencing antibiotic therapy and demonstrated at least one of
      the following: (i) a positive CSF culture of Neisseria meningitidis (n = 6); (ii)
      Gram negative diplococci on Gram stain (n = 16) or (iii) a positive CSF plasma
      clearance rate test for N. meningitidis (n = 26). RESULTS: Forty-eight children
      were identified with a mean age of 4.4 years. The cumulative dose of antibiotic
      prior to LP, ranged from 22 to 440 mg/kg body weight. All cases (n = 24) who
      received a cumulative dose of at least 150 mg/kg of antibiotic, prior to LP, had
      a sterile CSF. No CSF taken more than 5 h after commencing antibiotics grew N.
      meningitidis. CONCLUSIONS: Children in this study with MM had rapid sterilisation
      of the CSF in less than 6 h. This would support recent recommendations to reduce
      the duration of antibiotic therapy to 4 days. There is however, lack of long-term
      data on sequelae with 4 days of treatment.

PMID- 16630317
TI  - Clinical course of hospitalised children infected with human metapneumovirus and
      respiratory syncytial virus.
AB  - AIM: To describe the clinical presentation and outcomes of hospitalised patients
      infected with human metapneumovirus (hMPV) and human respiratory syncytial virus
      (hRSV) in a tertiary hospital in Cape Town, South Africa. METHODS: hMPV was
      identified in 17 respiratory specimens submitted for viral studies during the
      period 2001-2003. These patients' medical folders were retrospectively reviewed
      for clinical, radiological and laboratory data, together with a convenience
      sample of 20 hRSV-infected patients. RESULTS: hMPV-infected patients were older
      than those infected with hRSV (P = 0.04) and required a longer hospital stay (P =
      0.02). Presenting clinical signs and symptoms were similar between groups.
      Fourteen (87.5%) hMPV- and 16 (80%) hRSV-infected patients presented with co
      morbid and/or immunosuppressive conditions (P > or = 0.5). The most common
      abnormalities on chest radiographs in both groups were bronchial wall thickening,
      focal consolidation and atelectasis. Six (37.5%) hMPV- and 11 (55%) hRSV-infected
      patients required admission to the paediatric intensive care unit (P > 0.1) with
      five (31.3%) hMPV- and eight (40%) hRSV-infected patients requiring intubation
      and ventilation (P > 0.5). Three (18.7%) hMPV-patients and three (15%) hRSV
      infected patients died during this admission (P > 0.5). All hMPV-infected
      patients who died had significant co-morbid conditions. CONCLUSIONS: These data
      confirm that hMPV is a significant respiratory pathogen in this setting, with
      similar presentation and outcome to hRSV infection. This is the largest report of
      hMPV infection causing significant morbidity, prolonged hospital stay and death,
      associated with underlying risk factors.

PMID- 16630318
TI  - Doses of systemic corticosteroids in hospitalised children with acute asthma: A
      systematic review.
AB  - AIM: To present the doses of systemic corticosteroids reported by clinical trials
      in hospitalised children with acute asthma and to assess the possible
      relationship between doses of corticosteroids and clinical responses. METHODS: An
      electronic search of MEDLINE databases (January 1949-February 2005) and Cochrane
      Controlled Clinical Trials Register (February 2005) was undertaken using a
      combination of indexing terms related to systemic corticosteroids and acute
      asthma. Studies were selected if they met the following criteria: (i) randomized
      controlled trial; (ii) children aged 1-18 years and admitted to hospital for
      acute asthma; and (iii) treatment group consisting of systemic corticosteroids.
      RESULTS: Nine trials were included for this review. There was considerable
      variation between the reported doses of systemic corticosteroids. Only two trials
      assessed clinical responses to different doses of systemic corticosteroids. Both
      trials failed to show any therapeutic advantage of higher doses over lower doses.
      The results of the two trials were not suitable for pooling. CONCLUSIONS: Current
      data are not sufficient for establishing dose-response relationship of systemic
      corticosteroids in hospitalised children with acute asthma. Larger randomized
      trials are needed.

PMID- 16630319
TI  - Kawasaki disease in New Zealand.
AB  - AIM: To determine the epidemiology, management and outcome of Kawasaki disease
      (KD) in New Zealand. DESIGN: Prospective audit using New Zealand Paediatric
      Surveillance Unit (NZPSU) Reports. SETTING: Single country 2-year epidemiological
      study. PATIENTS: All patients diagnosed with KD in New Zealand reported to the
      NZPSU from January 2001 to December 2002. MAIN OUTCOME MEASURES: Incidence of KD;
      time to diagnosis; use of intravenous immunoglobulin; cardiac features and
      outcome. RESULTS: Forty-nine new cases were identified. The annual incidence was
      8.0 cases/100,000 children aged less than 5 years. Age at onset was less than 5
      years in 86% of cases. Incidence was 4.6/100,000 for children of European origin,
      9.6 for Maori, 12.2 for Pacific Islanders and 32.2 for children of East Asian
      origin. KD was diagnosed at a median of 6 days from onset of illness. 89% had
      fever and four or more diagnostic features. All patients had at least one
      echocardiogram: There was one small (2%) coronary artery aneurysm only; 13 (26%)
      had mild coronary artery dilatation. Thirty-five per cent did not have an
      echocardiogram performed four or more weeks from illness onset. 45 (92%) cases
      received intravenous immunoglobulin at median day six. There was one death due to
      occlusive coronary artery disease in a 3-month-old boy with atypical symptoms in
      whom KD was diagnosed at post-mortem. CONCLUSIONS: The incidence of KD in New
      Zealand is defined with significantly variable risk according to ethnicity. Most
      patients received appropriate rapid diagnosis and treatment but there was
      considerable variation in practice in regard to number and timing of
      echocardiograms. There was a low coronary artery aneurysm rate (2%). Accelerated
      vaso-occlusive disease was responsible for the single fatality in an atypical
      case.

PMID- 16630320
TI  - Hypoallergenic formula prescribing practices in Australia.
AB  - AIM: To gain insight into the use of hypoallergenic formula in Australia by
      analysis of prescribing statistics. METHODS: Statistics on supply of amino acid
      and extensively hydrolyzed formula were obtained from the Health Insurance
      Commission web site. The number of prescriptions supplied in 2003 and 2004 per
      1000 children aged 4 years and younger were calculated for each State and
      Territory. This was related to the numbers of paediatric physicians and
      paediatric allergists in each State. RESULTS: There was a marked rise in the use
      of amino acid formula (AAF) commencing in 2001. The Australian Capital Territory,
      New South Wales and Victoria had 6-7 times more AAF items per 1000 children
      prescribed than Western Australia. This did not appear to relate to the numbers
      of paediatricians or paediatric allergists in each State. In all States and
      Territories the prescribing of extensively hydrolyzed formula was less than that
      of AAF. CONCLUSIONS: There are significant regional differences which do not
      appear to be related to the prevalence of allergic disease. In some States and
      Territories AAF may be frequently prescribed as a first line treatment for cows
      milk allergy and for prevention of allergic disease in contradistinction to
      current recommendations of the Pharmaceutical Benefits Scheme and authoritative
      statements and position papers. Re-examination of both the Pharmaceutical Benefit
      Scheme guidelines and the knowledge and perceptions of the prescribing community
      is indicated.

PMID- 16630321
TI  - Rotavirus hospitalisation in New Zealand children under 3 years of age.
AB  - OBJECTIVE: To describe the epidemiology of severe rotavirus gastroenteritis and
      to estimate the hospitalisation rates of this illness in New Zealand children
      under 3 years of age. METHODS: Children under 3 years of age with acute diarrhoea
      admitted to 1 of 8 study hospitals between 1 May 1998 and 30 April 2000 were
      surveyed. Their socio-demographic, treatment and length-of-stay data were
      recorded and stool samples tested by a rotavirus-specific enzyme-linked
      immunoassay. National hospital discharge data for infectious diarrhoea
      (International Classification of Diseases, ninth revision, 003-009) were
      reviewed, allowing population-based estimates for rotavirus-related
      hospitalisation in New Zealand. RESULTS: Of 2019 enrolled children, 1138 (56.4%)
      provided stools for testing, and of these 485 (42.6%) tested rotavirus positive.
      Rotavirus detection varied significantly by age (26.8% for 0 to 5 months, 42.5%
      for 6 to 11 months and 52.1% for children aged 12 to 35 months; P < 0.001), and
      by season (51.2% in winter/spring vs. 24.5% in summer/autumn; P < 0.001). While
      those infected with rotavirus were more likely to be dehydrated (50.6% vs. 37.4%;
      P < 0.001), their median hospital stay was similar (1.0 vs. 2.0 days; P = 0.09)
      to other children with acute gastroenteritis. The estimated national
      hospitalisation rate for rotavirus diarrhoea in children under 3 years,
      standardised for age and season, was 634 (95% CI 597, 672) per 100,000. In New
      Zealand, rotaviruses result in 1 in 52 children being hospitalised by 3 years of
      age. CONCLUSIONS: Rotavirus diarrhoea is an important, potentially vaccine
      preventable cause of hospitalisation in New Zealand children, especially during
      winter and spring seasons.

PMID- 16630322
TI  - Antibiotic prescribing rates for acute otitis media in a paediatric emergency
      department.
AB  - OBJECTIVE: To audit antibiotic prescribing rates for acute otitis media (AOM) at
      a tertiary paediatric emergency department (ED). METHODS: All children who
      presented to the ED in 2002 (during defined 4-week periods in spring, summer,
      autumn and winter) and were given a diagnosis of AOM were eligible for analysis.
      Data were extracted retrospectively, providing information on demographics and
      antibiotic therapy. RESULTS: A total of 306 patients with AOM were available for
      analysis. Forty-three children (14%) were <1 year, 69 (23%) 1-2 years, and 194
      (63%) > 2 years of age. Sixty-eight patients (22%) were receiving antibiotics
      prior to presentation to the ED, and antibiotics were prescribed for 206 (67%).
      Antibiotic prescribing was independent of patient age. CONCLUSIONS: Despite ready
      access to clinical guidelines that recommend an expectant approach for children
      with AOM who are older than 1 or 2 years of age, antibiotic prescribing rates
      were high in the ED.

PMID- 16630323
TI  - Are general practitioners equipped to detect child overweight/obesity? Survey and
      audit.
AB  - AIM: To ascertain the extent to which general practitioners (GPs) routinely
      weigh, measure and calculate body mass index (BMI) in children, and to assess the
      accuracy and accessibility of their anthropometric equipment. METHODS: A
      convenience sample of 34 GPs from 29 primary care family medical practices in
      Melbourne, Australia, completed a questionnaire regarding their routine
      anthropometric practice for 5-10-year-old children and perceived role in managing
      childhood overweight and obesity. Practice audits (April-June 2002) assessed the
      accuracy and accessibility of anthropometric equipment. RESULTS: Forty-four per
      cent of GPs reported regularly weighing children; 38% regularly measured
      children's height. Only one regularly calculated children's BMI. Formal training
      in child anthropometry and servicing of anthropometric equipment was rare. The
      majority of equipment was accessible. Stadiometers on average measured the height
      of a 'short' pole (true height 92.68 cm) as 92.52 cm (SD = 0.8), and measured the
      height of a 'tall' pole (true height 157.64 cm) as 157.55 cm (SD = 0.9). On
      average, calibration weights of 20 kg and 80 kg were recorded as 19.7 kg (SD =
      0.6) and 79.2 kg (SD = 1.5) respectively. Despite these shortcomings, these GPs
      generally felt they played a key role in managing overweight in children.
      CONCLUSIONS: Self-reported practice by these GPs falls well short of 2003
      National Health and Medical Research Council guidelines recommending bi-annual
      measuring of all children in the primary care setting. The variability of
      anthropometric equipment audited could result in widely discrepant BMI values,
      leading to serious misclassification of many children's weight status.

PMID- 16630324
TI  - Vertebral collapse in an 8-year-old girl.
AB  - We present a case of an 8-year-old girl with collapse of her T6 and T7 vertebrae
      secondary to chronic recurrent multifocal osteomyelitis. She presented with
      chronic abdominal pain and was found to have multiple bony lesions involving her
      spine, clavicle and mandible. Extensive investigations, including tissue biopsy,
      were unable to identify an infective cause and there was no response to a
      prolonged course of intravenous antibiotics. She made a good response to regular
      non-steroidal anti-inflammatory medication.

PMID- 16630325
TI  - H-type tracheoesophageal fistula masquerading as achalasia cardia in a 13-year
      old child.
AB  - H-type tracheoesophageal fistula is rare. Although symptoms are present from
      birth, its rarity and overlap of symptoms with other respiratory conditions makes
      diagnosis difficult and delayed. We report a case of H-type fistula in a 13-year
      old girl that was detected incidentally during investigations for achalasia
      cardia.

PMID- 16630326
TI  - Unrecognised infection in a cystic fibrosis patient.
AB  - We report a 17-year-old Malay boy with cystic fibrosis who over a 14-month period
      experienced worsening respiratory symptoms and deteriorating lung function.
      Burkholderia pseudomallei was eventually isolated from his sputum. He improved
      clinically following treatment for meliodosis and his lung function returned to
      normal.

PMID- 16630327
TI  - Combination pharmacotherapy for severe neonatal pulmonary hypertension.
AB  - Pulmonary hypertension can complicate the early clinical course in newborn
      infants with congenital diaphragmatic hernia. We report the successful use of
      combination therapy with enteral sildenafil and intravenous prostaglandin E1 in a
      preterm infant with severe pulmonary hypertension and right heart failure early
      after congenital diaphragmatic hernia repair.

PMID- 16630328
TI  - Time for a change? Yes, but not to ciprofloxacin.

PMID- 16630330
TI  - Clinical need for ototopical fluoroquinolones outweighs miniscule risk of
      antibiotic resistance.

PMID- 16630334
TI  - Polyphyly and gene flow between non-sibling Heliconius species.
AB  - BACKGROUND: The view that gene flow between related animal species is rare and
      evolutionarily unimportant largely antedates sensitive molecular techniques. Here
      we use DNA sequencing to investigate a pair of morphologically and ecologically
      divergent, non-sibling butterfly species, Heliconius cydno and H. melpomene
      (Lepidoptera: Nymphalidae), whose distributions overlap in Central and
      Northwestern South America. RESULTS: In these taxa, we sequenced 30-45 haplotypes
      per locus of a mitochondrial region containing the genes for cytochrome oxidase
      subunits I and II (CoI/CoII), and intron-spanning fragments of three unlinked
      nuclear loci: triose-phosphate isomerase (Tpi), mannose-6-phosphate isomerase
      (Mpi) and cubitus interruptus (Ci) genes. A fifth gene, dopa decarboxylase (Ddc)
      produced sequence data likely to be from different duplicate loci in some of the
      taxa, and so was excluded. Mitochondrial and Tpi genealogies are consistent with
      reciprocal monophyly, whereas sympatric populations of the species in Panama
      share identical or similar Mpi and Ci haplotypes, giving rise to genealogical
      polyphyly at the species level despite evidence for rapid sequence divergence at
      these genes between geographic races of H. melpomene. CONCLUSION: Recent transfer
      of Mpi haplotypes between species is strongly supported, but there is no evidence
      for introgression at the other three loci. Our results demonstrate that the
      boundaries between animal species can remain selectively porous to gene flow long
      after speciation, and that introgression, even between non-sibling species, can
      be an important factor in animal evolution. Interspecific gene flow is
      demonstrated here for the first time in Heliconius and may provide a route for
      the transfer of switch-gene adaptations for Mullerian mimicry. The results also
      forcefully demonstrate how reliance on a single locus may give an erroneous
      picture of the overall genealogical history of speciation and gene flow.

PMID- 16630335
TI  - Prevention of coronary heart disease in people with severe mental illnesses: a
      qualitative study of patient and professionals' preferences for care.
AB  - BACKGROUND: People with severe mental illness (SMI) are at increased risk of
      developing coronary heart disease (CHD) and there is growing emphasis on the need
      to monitor their physical health. However, there is little consensus on how
      services for the primary prevention of CHD should be organised for this patient
      group. We explored the views of people with SMI and health professionals from
      primary care and community mental health teams (CMHTs) on how best to provide
      these services. METHODS: In-depth interviews were conducted with a purposive
      sample of patients with SMI (n = 31) and staff from primary care (n = 10) and
      community mental health teams (n = 25) in North Central London. Transcripts of
      the qualitative interviews were analysed using a 'framework' approach to identify
      the main themes in opinions regarding various service models. RESULTS:
      Cardiovascular risk factors in people with SMI were of concern to participants.
      However, there was some disagreement about the best way to deliver appropriate
      care. Although staff felt that primary care should take responsibility for risk
      factor screening and management, patients favoured CHD screening in their CMHT.
      Problems with both approaches were identified. These included a lack of
      familiarity in general practice with SMI and antipsychotic side effects and poor
      communication of physical health issues to the CMHT. Lack of knowledge regarding
      CHD risk factor screening and difficulties in interpreting screening results and
      implementing appropriate interventions exist in secondary care. CONCLUSION:
      Management of physical health care for people with SMI requires complex solutions
      that cross the primary-secondary care interface. The views expressed by our
      participants suggest that neither primary nor secondary care services on their
      own can provide a comprehensive service for all patients. The increased risk of
      CHD associated with SMI and antipsychotic medications requires flexible solutions
      with clear lines of responsibility for assessing, communicating and managing CHD
      risks.

PMID- 16630337
TI  - Occupational pesticide intoxications among farmers in Bolivia: a cross-sectional
      study.
AB  - BACKGROUND: Pesticide use and its consequences are of concern in Bolivia due to
      an intensive and increasing use. METHODS: To assess the magnitude and reasons for
      occupational pesticide intoxication, a cross-sectional study with interviews and
      blood-tests was performed among 201 volunteer farmers from 48 villages in the
      temperate and subtropical valleys in the eastern part of the Andes Mountains in
      Bolivia. Of these 171 male farmers using pesticides in their agricultural
      production were used in the statistical analysis, including linear- and logistic
      regression analysis. RESULTS: This study documented a frequent use of the most
      toxic pesticides among farmers who have had almost no instructions in how to use
      pesticides and protect themselves against the dangers of intoxication, reflected
      in the hazardous practices used when handling pesticides. Symptoms of
      intoxications were common in connection with spraying operations. The risk of
      experiencing symptoms and the serum cholinesterase activity were influenced by
      whether or not organophosphates were used and the number of times sprayed. The
      experience of symptoms was moreover influenced by the hygienic and personal
      protective measures taken during spraying operations while this had no influence
      on the serum cholinesterase level. CONCLUSION: The study showed that occupational
      pesticide intoxications were common among farmers and did depend on multiple
      factors. Pesticide use is probably one of the largest toxicological problems in
      Bolivia, and a coordinated action by authorities, society and international
      bodies is needed to limit the number of intoxications and the environmental
      pollution.

PMID- 16630336
TI  - Do teachers have more health problems? Results from a French cross-sectional
      survey.
AB  - BACKGROUND: Although only a few studies have been published on teachers' health,
      certain ideas are widely accepted, such as for example, the preconceived notion
      that teachers suffer from an excessively high rate of mental health problems. The
      objective of this study is to compare teachers' mental and physical health to
      that of a control group. METHODS: A cross-sectional postal survey was conducted
      among a sample of 3,679 teachers and 1,817 non-teachers aged 20 to 60 years old.
      RESULTS: No lifetime prevalence of any psychiatric disorder (with the exception
      of undifferentiated somatoform disorder in men) or mean scores of psychological
      distress were found to be significantly higher in teachers. However, multiple
      analyses, adjusted for all confounding variables, revealed a higher risk of
      lifetime anxiety disorders in male teachers. On the other hand, significant
      differences were observed for some physical ailments: a higher lifetime
      prevalence of rhinopharyngitis/laryngitis in both male and female teachers, of
      conjunctivitis and lower urinary tract infection in male teachers and of
      bronchitis, eczema/dermatitis and varicose veins in female teachers. No
      significant difference was found for chronic pain between the two groups.
      CONCLUSION: Teachers do not seem to have poorer mental health. However, their
      physical condition is characterized by a higher prevalence of health problems
      related to the ENT tract, and to a lesser extent, depending on the gender, to
      skin, eyes, legs and lower urinary tract.

PMID- 16630338
TI  - Are there differences in all-cause and coronary heart disease mortality between
      immigrants in Sweden and in their country of birth? A follow-up study of total
      populations.
AB  - BACKGROUND: Mortality from cardiovascular diseases is higher among immigrants
      than native Swedes. It is not clear whether the high mortality persists from the
      country of birth or is a result of migration. The purpose of the present study
      was to analyse whether all-cause and coronary heart disease mortality differ
      between immigrants in Sweden and in the country of birth. METHODS: Two cohorts
      including the total population from Swedish national registers and WHO were
      defined. All-cause and CHD mortality are presented as age-adjusted incidence
      rates and incidence density ratios (IDR) in eight immigrant groups in Sweden and
      in their country of birth. The data were analysed using Poisson regression.
      RESULTS: The all-cause mortality risk was lower among seven of eight male
      immigrant groups (IDR 0.39-0.97) and among six of eight female immigrant groups
      (IDR 0.42-0.81) than in their country of birth. The CHD mortality risk was
      significantly lower in male immigrants from Norway (IDR = 0.84), Finland (IDR =
      0.91), Germany (IDR = 0.84) and Hungary (IDR = 0.59) and among female immigrants
      from Germany (IDR = 0.66) and Hungary (IDR = 0.54) than in their country of
      birth. In contrast, there was a significantly higher CHD mortality risk in male
      immigrants from Southern Europe (IDR = 1.23) than in their country of birth.
      CONCLUSION: The all-cause mortality risk was lower in the majority of immigrant
      groups in Sweden than in their country of birth. The differences in CHD mortality
      risks were more complex. For countries with high CHD mortality, such as Finland
      and Hungary, the risk was lower among immigrants in Sweden than in their country
      of birth. For low-risk countries in South Europe, the risk was higher in
      immigrants in Sweden than in South Europe.

PMID- 16630339
TI  - Prenatal origin of childhood AML occurs less frequently than in childhood ALL.
AB  - BACKGROUND: While there is enough convincing evidence in childhood acute
      lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute
      myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie
      cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the
      presence of their respective leukemic markers. METHODS: We analysed Guthrie cards
      of 12 ALL patients aged 2-6 years using immunoglobulin (Ig) and T-cell receptor
      (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion
      gene (n = 3). In AML patients (n = 13, age 1-14 years) PML/RARalpha (n = 4),
      CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and
      MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene
      (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined
      using serial dilutions of patient DNA into the DNA of a healthy donor allowed us
      to detect the pre-leukemic clone in Guthrie card providing 1-3 positive cells
      were present in the neonatal blood spot. RESULTS: In 3 patients with ALL (25%) we
      reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in
      the Guthrie card. We did not find patient-specific molecular markers in any
      patient with AML. CONCLUSION: In the largest cohort examined so far we used
      identical approach for the backtracking of non-infant childhood ALL and AML. Our
      data suggest that either the prenatal origin of AML is less frequent or the load
      of pre-leukemic cells is significantly lower at birth in AML compared to ALL
      cases.

PMID- 16630340
TI  - The challenge for genetic epidemiologists: how to analyze large numbers of SNPs
      in relation to complex diseases.
AB  - Genetic epidemiologists have taken the challenge to identify genetic
      polymorphisms involved in the development of diseases. Many have collected data
      on large numbers of genetic markers but are not familiar with available methods
      to assess their association with complex diseases. Statistical methods have been
      developed for analyzing the relation between large numbers of genetic and
      environmental predictors to disease or disease-related variables in genetic
      association studies. In this commentary we discuss logistic regression analysis,
      neural networks, including the parameter decreasing method (PDM) and genetic
      programming optimized neural networks (GPNN) and several non-parametric methods,
      which include the set association approach, combinatorial partitioning method
      (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction
      (MDR) method and the random forests approach. The relative strengths and
      weaknesses of these methods are highlighted. Logistic regression and neural
      networks can handle only a limited number of predictor variables, depending on
      the number of observations in the dataset. Therefore, they are less useful than
      the non-parametric methods to approach association studies with large numbers of
      predictor variables. GPNN on the other hand may be a useful approach to select
      and model important predictors, but its performance to select the important
      effects in the presence of large numbers of predictors needs to be examined. Both
      the set association approach and random forests approach are able to handle a
      large number of predictors and are useful in reducing these predictors to a
      subset of predictors with an important contribution to disease. The combinatorial
      methods give more insight in combination patterns for sets of genetic and/or
      environmental predictor variables that may be related to the outcome variable. As
      the non-parametric methods have different strengths and weaknesses we conclude
      that to approach genetic association studies using the case-control design, the
      application of a combination of several methods, including the set association
      approach, MDR and the random forests approach, will likely be a useful strategy
      to find the important genes and interaction patterns involved in complex
      diseases.

PMID- 16630341
TI  - Differential regulation of NF-kappaB activation and function by topoisomerase II
      inhibitors.
AB  - BACKGROUND: While many common chemotherapeutic drugs and other inducers of DNA
      damage result in both NF-kappaB nuclear translocation and DNA-binding, we have
      previously observed that, depending on the precise stimulus, there is great
      diversity of the function of NF-kappaB. In particular, we found that treatment of
      U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet
      (UV-C) light resulted in a form of NF-kappaB that repressed rather than induced
      NF-kappaB reporter plasmids and the expression of specific anti-apoptotic genes.
      Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting
      topoisomerase II, intercalating with DNA and undergoing redox cycling to produce
      oxygen free radicals. In this study we have investigated other anthracyclines,
      doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together
      with the topoisomerase II inhibitor ICRF-193, which all possess differing
      characteristics, to determine which of these features is specifically required to
      induce both NF-kappaB DNA-binding and transcriptional repression in U-2 OS cells.
      RESULTS: The use of mitoxantrone, which does not undergo redox cycling, and the
      reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free
      radical production is not required for induction of NF-kappaB DNA-binding and
      transcriptional repression by these agents and UV-C. In addition, the use of
      aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which
      inhibits topoisomerase II but does not intercalate into DNA, demonstrated that
      topoisomerase II inhibition is not sufficient to induce the repressor form of NF
      kappaB. CONCLUSION: Induction of NF-kappaB DNA-binding and transcriptional
      repression by topoisomerase II inhibitors was found to correlate with an ability
      to intercalate into DNA. Although data from our and other laboratories indicates
      that topoisomerase II inhibition and oxygen free radicals do regulate NF-kappaB,
      they are not required for the particular ability of NF-kappaB to repress rather
      than activate transcription. Together with our previous data, these results
      demonstrate that the nature of the NF-kappaB response is context dependent. In a
      clinical setting such effects could profoundly influence the response to
      chemotherapy and suggest that new methods of analyzing NF-kappaB function could
      have both diagnostic and prognostic value.

PMID- 16630342
TI  - Efficacy and safety of acupuncture for the treatment of non-specific acute low
      back pain: a randomised controlled multicentre trial protocol [ISRCTN65814467].
AB  - BACKGROUND: Low back pain and its associated incapacitating effects constitute an
      important healthcare and socioeconomic problem, as well as being one of the main
      causes of disability among adults of working age. The prevalence of non-specific
      low back pain is very high among the general population, and 60-70% of adults are
      believed to have suffered this problem at some time. Nevertheless, few randomised
      clinical trials have been made of the efficacy and efficiency of acupuncture with
      respect to acute low back pain. The present study is intended to assess the
      efficacy of acupuncture for acute low back pain in terms of the improvement
      reported on the Roland Morris Questionnaire (RMQ) on low back pain incapacity, to
      estimate the specific and non-specific effects produced by the technique, and to
      carry out a cost-effectiveness analysis. METHODS/DESIGN: Randomised four-branch
      controlled multicentre prospective study made to compare semi-standardised real
      acupuncture, sham acupuncture (acupuncture at non-specific points), placebo
      acupuncture and conventional treatment. The patients are blinded to the real,
      sham and placebo acupuncture treatments. Patients in the sample present symptoms
      of non specific acute low back pain, with a case history of 2 weeks or less, and
      will be selected from working-age patients, whether in paid employment or not,
      referred by General Practitioners from Primary Healthcare Clinics to the four
      clinics participating in this study. In order to assess the primary and secondary
      result measures, the patients will be requested to fill in a questionnaire before
      the randomisation and again at 3, 12 and 48 weeks after starting the treatment.
      The primary result measure will be the clinical relevant improvement (CRI) at 3
      weeks after randomisation. We define CRI as a reduction of 35% or more in the RMQ
      results. DISCUSSION: This study is intended to obtain further evidence on the
      effectiveness of acupuncture on acute low back pain and to isolate the specific
      and non-specific effects of the treatment.

PMID- 16630343
TI  - A factor analysis model for functional genomics.
AB  - BACKGROUND: Expression array data are used to predict biological functions of
      uncharacterized genes by comparing their expression profiles to those of
      characterized genes. While biologically plausible, this is both statistically and
      computationally challenging. Typical approaches are computationally expensive and
      ignore correlations among expression profiles and functional categories. RESULTS:
      We propose a factor analysis model (FAM) for functional genomics and give a two
      step algorithm, using genome-wide expression data for yeast and a subset of Gene
      Ontology Biological Process functional annotations. We show that the predictive
      performance of our method is comparable to the current best approach while our
      total computation time was faster by a factor of 4000. We discuss the unique
      challenges in performance evaluation of algorithms used for genome-wide functions
      genomics. Finally, we discuss extensions to our method that can incorporate the
      inherent correlation structure of the functional categories to further improve
      predictive performance. CONCLUSION: Our factor analysis model is a
      computationally efficient technique for functional genomics and provides a clear
      and unified statistical framework with potential for incorporating important gene
      ontology information to improve predictions.

PMID- 16630344
TI  - The PedsQL as a patient-reported outcome in children and adolescents with
      Attention-Deficit/Hyperactivity Disorder: a population-based study.
AB  - BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common
      chronic mental health condition in children and adolescents. The application of
      health-related quality of life (HRQOL) as a pediatric population health measure
      may facilitate risk assessment and resource allocation, the identification of
      health disparities, and the determination of health outcomes from interventions
      and policy decisions for children and adolescents with ADHD at the local
      community, state, and national health level. METHODS: An analysis from an
      existing statewide database to determine the feasibility, reliability, and
      validity of the 23-item PedsQL 4.0 (Pediatric Quality of Life Inventory) Generic
      Core Scales as a patient-reported outcome (PRO) measure of pediatric population
      health for children and adolescents with ADHD. The PedsQL 4.0 Generic Core Scales
      (Physical, Emotional, Social, School Functioning) were completed by families
      through a statewide mail survey to evaluate the HRQOL of new enrollees in the
      State of California State's Children's Health Insurance Program (SCHIP). Seventy
      two children ages 5-16 self-reported their HRQOL. RESULTS: The PedsQL 4.0
      evidenced minimal missing responses, achieved excellent reliability for the Total
      Scale Score (alpha = 0.92 child self-report, 0.92 parent proxy-report), and
      distinguished between healthy children and children with ADHD. Children with ADHD
      self-reported severely impaired psychosocial functioning, comparable to children
      with newly-diagnosed cancer and children with cerebral palsy. CONCLUSION: The
      results suggest that population health monitoring may identify children with ADHD
      at risk for adverse HRQOL. The implications of measuring pediatric HRQOL for
      evaluating the population health outcomes of children with ADHD internationally
      are discussed.

PMID- 16630345
TI  - Predicting deleterious nsSNPs: an analysis of sequence and structural attributes.
AB  - BACKGROUND: There has been an explosion in the number of single nucleotide
      polymorphisms (SNPs) within public databases. In this study we focused on non
      synonymous protein coding single nucleotide polymorphisms (nsSNPs), some
      associated with disease and others which are thought to be neutral. We describe
      the distribution of both types of nsSNPs using structural and sequence based
      features and assess the relative value of these attributes as predictors of
      function using machine learning methods. We also address the common problem of
      balance within machine learning methods and show the effect of imbalance on nsSNP
      function prediction. We show that nsSNP function prediction can be significantly
      improved by 100% undersampling of the majority class. The learnt rules were then
      applied to make predictions of function on all nsSNPs within Ensembl. RESULTS:
      The measure of prediction success is greatly affected by the level of imbalance
      in the training dataset. We found the balanced dataset that included all
      attributes produced the best prediction. The performance as measured by the
      Matthews correlation coefficient (MCC) varied between 0.49 and 0.25 depending on
      the imbalance. As previously observed, the degree of sequence conservation at the
      nsSNP position is the single most useful attribute. In addition to conservation,
      structural predictions made using a balanced dataset can be of value. CONCLUSION:
      The predictions for all nsSNPs within Ensembl, based on a balanced dataset using
      all attributes, are available as a DAS annotation. Instructions for adding the
      track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html.

PMID- 16630346
TI  - XcisClique: analysis of regulatory bicliques.
AB  - BACKGROUND: Modeling of cis-elements or regulatory motifs in promoter (upstream)
      regions of genes is a challenging computational problem. In this work, set of
      regulatory motifs simultaneously present in the promoters of a set of genes is
      modeled as a biclique in a suitably defined bipartite graph. A biologically
      meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed
      by the combined analysis of genomic and gene expression data. Greater statistical
      significance is associated with a set of genes that shares a common set of
      regulatory motifs, while simultaneously exhibiting highly correlated gene
      expression under given experimental conditions. METHODS: XcisClique, the system
      developed in this work, is a comprehensive infrastructure that associates
      annotated genome and gene expression data, models known cis-elements as regular
      expressions, identifies maximal bicliques in a bipartite gene-motif graph; and
      ranks bicliques based on their computed statistical significance. Significance is
      a function of the probability of occurrence of those motifs in a biclique (a
      hypergeometric distribution), and on the new sum of absolute values statistic
      (SAV) that uses Spearman correlations of gene expression vectors. SAV is a
      statistic well-suited for this purpose as described in the discussion. RESULTS:
      XcisClique identifies new motif and gene combinations that might indicate as yet
      unidentified involvement of sets of genes in biological functions and processes.
      It currently supports Arabidopsis thaliana and can be adapted to other organisms,
      assuming the existence of annotated genomic sequences, suitable gene expression
      data, and identified regulatory motifs. A subset of Xcis Clique functionalities,
      including the motif visualization component MotifSee, source code, and
      supplementary material are available at
      https://bioinformatics.cs.vt.edu/xcisclique/.

PMID- 16630347
TI  - Exploration of biological network centralities with CentiBiN.
AB  - BACKGROUND: The elucidation of whole-cell regulatory, metabolic, interaction and
      other biological networks generates the need for a meaningful ranking of network
      elements. Centrality analysis ranks network elements according to their
      importance within the network structure and different centrality measures focus
      on different importance concepts. Central elements of biological networks have
      been found to be, for example, essential for viability. RESULTS: CentiBiN
      (Centralities in Biological Networks) is a tool for the computation and
      exploration of centralities in biological networks such as protein-protein
      interaction networks. It computes 17 different centralities for directed or
      undirected networks, ranging from local measures, that is, measures that only
      consider the direct neighbourhood of a network element, to global measures.
      CentiBiN supports the exploration of the centrality distribution by visualising
      central elements within the network and provides several layout mechanisms for
      the automatic generation of graphical representations of a network. It supports
      different input formats, especially for biological networks, and the export of
      the computed centralities to other tools. CONCLUSION: CentiBiN helps systems
      biology researchers to identify crucial elements of biological networks. CentiBiN
      including a user guide and example data sets is available free of charge at
      http://centibin.ipk-gatersleben.de/. CentiBiN is available in two different
      versions: a Java Web Start application and an installable Windows application.

PMID- 16630348
TI  - Retrieval with gene queries.
AB  - BACKGROUND: Accuracy of document retrieval from MEDLINE for gene queries is
      crucially important for many applications in bioinformatics. We explore five
      information retrieval-based methods to rank documents retrieved by PubMed gene
      queries for the human genome. The aim is to rank relevant documents higher in the
      retrieved list. We address the special challenges faced due to ambiguity in gene
      nomenclature: gene terms that refer to multiple genes, gene terms that are also
      English words, and gene terms that have other biological meanings. RESULTS: Our
      two baseline ranking strategies are quite similar in performance. Two of our
      three LocusLink-based strategies offer significant improvements. These methods
      work very well even when there is ambiguity in the gene terms. Our best ranking
      strategy offers significant improvements on three different kinds of ambiguities
      over our two baseline strategies (improvements range from 15.9% to 17.7% and
      11.7% to 13.3% depending on the baseline). For most genes the best ranking query
      is one that is built from the LocusLink (now Entrez Gene) summary and product
      information along with the gene names and aliases. For others, the gene names and
      aliases suffice. We also present an approach that successfully predicts, for a
      given gene, which of these two ranking queries is more appropriate. CONCLUSION:
      We explore the effect of different post-retrieval strategies on the ranking of
      documents returned by PubMed for human gene queries. We have successfully applied
      some of these strategies to improve the ranking of relevant documents in the
      retrieved sets. This holds true even when various kinds of ambiguity are
      encountered. We feel that it would be very useful to apply strategies like ours
      on PubMed search results as these are not ordered by relevance in any way. This
      is especially so for queries that retrieve a large number of documents.

PMID- 16630349
TI  - Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo
      Verde: implications for potential large-scale re-emergence of malaria.
AB  - BACKGROUND: Malaria has come near eradication at archipelago of Cabo Verde in
      1970. Infections are now only observed in Santiago, where outbreaks occur. In
      these islands, malaria is considered by the international community as being of
      limited risk and, therefore, no prophylaxis is recommended. Since the
      understanding of factors that determine malaria outbreaks are crucial for
      controlling the disease, the present study aimed to investigate if the malaria
      infections observed in Santiago Island are maintained in isolated foci and in
      asymptomatic individuals. METHODS: The occurrence of asymptomatic carriers in
      villages with history of malaria as well as the level of exposure of these
      populations were investigated using PCR and serological analyses. RESULTS:
      Results indicate that malaria is maintained as asymptomatic and sub-patent
      infections and that the majority of the circulating parasite populations harbour
      chloroquine-resistant mutations. CONCLUSION: These observations highlight the
      alarming prospect of malaria to become a serious public health problem and
      underscore the need for a tighter surveillance.

PMID- 16630350
TI  - The complete plastid genome sequence of the parasitic green alga Helicosporidium
      sp. is highly reduced and structured.
AB  - BACKGROUND: Loss of photosynthesis has occurred independently in several plant
      and algal lineages, and represents a major metabolic shift with potential
      consequences for the content and structure of plastid genomes. To investigate
      such changes, we sequenced the complete plastid genome of the parasitic, non
      photosynthetic green alga, Helicosporidium. RESULTS: The Helicosporidium plastid
      genome is among the smallest known (37.5 kb), and like other plastids from non
      photosynthetic organisms it lacks all genes for proteins that function in
      photosynthesis. Its reduced size results from more than just loss of genes,
      however; it has little non-coding DNA, with only one intron and tiny intergenic
      spaces, and no inverted repeat (no duplicated genes at all). It encodes precisely
      the minimal complement of tRNAs needed to translate the universal genetic code,
      and has eliminated all redundant isoacceptors. The Helicosporidium plastid genome
      is also highly structured, with each half of the circular genome containing
      nearly all genes on one strand. Helicosporidium is known to be related to
      trebouxiophyte green algae, but the genome is structured and compacted in a
      manner more reminiscent of the non-photosynthetic plastids of apicomplexan
      parasites. CONCLUSION: Helicosporidium contributes significantly to our
      understanding of the evolution of plastid DNA because it illustrates the highly
      ordered reduction that occurred following the loss of a major metabolic function.
      The convergence of plastid genome structure in Helicosporidium and the
      Apicomplexa raises the interesting possibility that there are common forces that
      shape plastid genomes, subsequent to the loss of photosynthesis in an organism.

PMID- 16630351
TI  - The effects of smoking and hypertensive disorders on fetal growth.
AB  - BACKGROUND: It is well known that smoking and pregnancy induced hypertension
      (PIH) are associated with decreased fetal growth. It has been reported that in
      preeclampsia the fetal growth deficit attributable to smoking is higher, which
      has been contradicted in other studies. We therefore evaluated the effects on
      fetal growth of early- and late onset PIH and chronic hypertension and how
      cigarette smoking modify these effects. We also quantified the proportion of
      small for gestational age (SGA) cases attributable to PIH, chronic hypertension,
      and smoking. METHODS: Population-based study based on record of 215598 singleton
      pregnancies from the Medical Birth Registry of Norway. RESULTS: In severe
      preeclampsia, mild preeclampsia, transient hypertension, and normotension in term
      birth, odds ratios (ORs) of SGA in smokers compared with non-smokers were 1.4
      (95% confidence interval 0.9, 2.2), 1.6 (1.3, 1.9), 2.3 (1.8, 3.1), and 2.0 (1.9,
      2.1), respectively. For preterm births, corresponding ORs were 1.3 (0.9, 2.0),
      1.8 (1.1, 3.0), 4.1 (1.9, 9.0), and 1.7 (1.4, 2.0), respectively. The effect of
      early onset PIH was stronger than that in term births, while the effect of
      smoking was equal in preterm and term newborns. Only in non-smokers who delivered
      at term, the rates of SGA significantly increased with the severity of PIH (ORs =
      1.3 (1.1, 1.5), 1.8 (1.7, 2.0), and 2.5 (2.2, 3.0) for transient hypertension,
      mild-, and severe preeclampsia, respectively). The combined effects of smoking
      and hypertension were generally not synergistic. The effect of smoking was not
      stronger in women who had chronic hypertension. Nor were the effects of chronic
      hypertension stronger in smokers. PIH explained 21.9 and 2.5% of preterm and term
      cases of SGA, respectively, while smoking explained 12% of SGA cases. CONCLUSION:
      The effects of hypertensive disorder and smoking were generally not synergistic,
      which suggest that they may exert their main actions on separate sites or work
      through separate mechanisms within or outside the placenta. If smoking were
      eliminated in pregnant women, the number of SGA cases would be reduced by 12%.

PMID- 16630352
TI  - In-vitro activity of polymyxin B in combination with imipenem, rifampicin and
      azithromycin versus multidrug resistant strains of Acinetobacter baumannii
      producing OXA-23 carbapenemases.
AB  - BACKGROUND: Acinetobacter baumannii has emerged as a major nosocomial pathogen
      worldwide. Many of the circulating strains exhibit multi-drug resistance
      remaining consistently susceptible only to polymyxins. In-vitro studies have
      reported that polymyxins combined with carbapenems, rifampicin or azithromycin
      are synergistic against these strains despite in-vitro resistance to these agents
      alone. The use of antimicrobial combinations have therefore been advocated for
      the treatment of severe A. baumannii infection in man. In order to determine
      whether such combinations are synergistic against the prevalent clones of multi
      drug resistant A. baumannii causing infection in the UK, we performed synergy
      testing against representative isolates using two rapid Etest methods. METHODS:
      The activity of polymyxin in combination with imipenem, azithromycin or
      rifampicin was assessed against five strains of multi-drug resistant A. baumannii
      encoding OXA-23 carbapenemases. Synergy studies were performed by Etest-agar
      dilution and a combined Etest strip method. Synergy was defined as a FICI of < or
      = 0.5. RESULTS: All strains were resistant to beta-lactams, carbapenems,
      quinolones and aminoglycosides but susceptible to polymyxins. Marked synergy was
      not seen with polymyxin in combination with imipenem, rifampicin or azithromycin
      against any of the strains. Borderline synergy (FICI = 0.5) was seen against one
      strain belonging to OXA-23 clonal group 2, using the Etest-agar dilution method
      only. CONCLUSION: In-vitro synergy with polymxyin in combination with imipenem,
      rifampicin or azithromycin is highly strain and method dependent. As reliable
      synergy could not be demonstrated against the prevalent UK multi-drug resistant
      strains, use of such combinations should not be used for empirical treatment of
      these infections in the UK. The optimal treatment for serious multi-drug A.
      baumannii infection and the role of combination therapy should be addressed in a
      prospective clinical trial.

PMID- 16630353
TI  - Thrombin generation by activated factor VII on platelet activated by different
      agonists. Extending the cell-based model of hemostasis.
AB  - BACKGROUND: Platelet activation is crucial in normal hemostasis. Using a clotting
      system free of external tissue factor, we investigated whether activated Factor
      VII in combination with platelet agonists increased thrombin generation (TG) in
      vitro. METHODS AND RESULTS: TG was quantified by time parameters: lag time (LT)
      and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under
      thrombin formation curve after 35 minutes (AUC-->35min) in plasma from 29 healthy
      volunteers using the calibrated automated thrombography (CAT) technique. TG
      parameters were measured at basal conditions and after platelet stimulation by
      sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of
      recombinant activated FVII (rFVIIa) alone or combined with the other platelet
      agonists on TG parameters were investigated. We found that LT and TTP were
      significantly decreased (p < 0.05) and PTG and AUC-->35min were significantly
      increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and
      rFVIIa compared to non-activated platelet rich plasma from normal subjects (p =
      0.01). Furthermore platelet rich plasma activated by the combined effects of
      rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC
      ->35min (but not PTG) when compared to platelet rich plasma activated with
      agonists in the absence of rFVIIa. CONCLUSION: Platelets activated by AA, ADP,
      Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with
      other agonists. Our intrinsic coagulation system produced a burst in TG
      independent of external tissue factor activity an apparent hemostatic effect with
      little thrombotic capacity. Thus we suggest a modification in the cell-based
      model of hemostasis.

PMID- 16630354
TI  - Pathogen detection, testing, and control in fresh broccoli sprouts.
AB  - BACKGROUND: The recent increased interest in consuming green vegetable sprouts
      has been tempered by the fact that fresh sprouts can in some cases be vehicles
      for food-borne illnesses. They must be grown according to proper conditions of
      sanitation and handled as a food product rather than as an agricultural
      commodity. When sprouts are grown in accordance with the criteria proposed from
      within the sprout industry, developed by regulatory agencies, and adhered to by
      many sprouters, green sprouts can be produced with very low risk. Contamination
      may occur when these guidelines are not followed. METHODS: A one year program of
      microbial hold-and-release testing, conducted in concert with strict seed and
      facility cleaning procedures by 13 U.S. broccoli sprout growers was evaluated.
      Microbial contamination tests were performed on 6839 drums of sprouts, equivalent
      to about 5 million consumer packages of fresh green sprouts. RESULTS: Only 24
      (0.75%) of the 3191 sprout samples gave an initial positive test for Escherichia
      coli O157:H7 or Salmonella spp., and when re-tested, 3 drums again tested
      positive. Composite testing (e.g., pooling up to 7 drums for pathogen testing)
      was equally sensitive to single drum testing. CONCLUSION: By using a "test-and-re
      test" protocol, growers were able to minimize crop destruction. By pooling drums
      for testing, they were also able to reduce testing costs which now represent a
      substantial portion of the costs associated with sprout growing. The test-and
      hold scheme described herein allowed those few batches of contaminated sprouts to
      be found prior to packaging and shipping. These events were isolated, and only
      safe sprouts entered the food supply.

PMID- 16630355
TI  - Operon information improves gene expression estimation for cDNA microarrays.
AB  - BACKGROUND: In prokaryotic genomes, genes are organized in operons, and the genes
      within an operon tend to have similar levels of expression. Because of co
      transcription of genes within an operon, borrowing information from other genes
      within the same operon can improve the estimation of relative transcript levels;
      the estimation of relative levels of transcript abundances is one of the most
      challenging tasks in experimental genomics due to the high noise level in
      microarray data. Therefore, techniques that can improve such estimations, and
      moreover are based on sound biological premises, are expected to benefit the
      field of microarray data analysis RESULTS: In this paper, we propose a
      hierarchical Bayesian model, which relies on borrowing information from other
      genes within the same operon, to improve the estimation of gene expression levels
      and, hence, the detection of differentially expressed genes. The simulation
      studies and the analysis of experiential data demonstrated that the proposed
      method outperformed other techniques that are routinely used to estimate
      transcript levels and detect differentially expressed genes, including the sample
      mean and SAM t statistics. The improvement became more significant as the noise
      level in microarray data increases. CONCLUSION: By borrowing information about
      transcriptional activity of genes within classified operons, we improved the
      estimation of gene expression levels and the detection of differentially
      expressed genes.

PMID- 16630356
TI  - Evaluation of phage assay for rapid phenotypic detection of rifampicin resistance
      in Mycobacterium tuberculosis.
AB  - BACKGROUND: Conventional methods for susceptibility testing require several
      months before results can be reported. However, rapid methods to determine drug
      susceptibility have been developed recently. Phage assay have been reported as a
      rapid useful tools for antimicrobial susceptibility testing. The aim of this
      study was to apply the Phage assay for rapid detection of resistance on
      Mycobacterium tuberculosis strains in Cuba. METHODS: Phage D29 assay was
      performed on 102 M. tuberculosis strains to detect rifampicin resistance. The
      results were compared with the proportion method (gold standard) to evaluate the
      sensitivity and specificity of Phage assay. RESULTS: Phage assay results were
      available in 2 days whereas Proportion Methods results were obtain in 42 days. A
      total of 44 strains were detected as rifampicin resistant by both methods.
      However, one strains deemed resistant by Proportion Methods was susceptible by
      Phage assay. The sensitivity and specificity of Phage assay were 97.8 % and 100%
      respectively. CONCLUSION: Phage assay provides rapid and reliable results for
      susceptibility testing; it's easy to perform, requires no specialized equipment
      and is applicable to drug susceptibility testing in low income countries where
      tuberculosis is a major public health problem.

PMID- 16630357
TI  - Transcriptional analysis of the bglP gene from Streptococcus mutans.
AB  - BACKGROUND: An open reading frame encoding a putative antiterminator protein,
      LicT, was identified in the genomic sequence of Streptococcus mutans. A potential
      ribonucleic antitermination (RAT) site to which the LicT protein would
      potentially bind has been identified immediately adjacent to this open reading
      frame. The licT gene and RAT site are both located 5' to a beta-glucoside PTS
      regulon previously described in S. mutans that is responsible for esculin
      utilization in the presence of glucose. It was hypothesized that antitermination
      is the regulatory mechanism that is responsible for the control of the bglP gene
      expression, which encodes an esculin-specific PTS enzyme II. RESULTS: To localize
      the promoter activity associated with the bglP locus, a series of transcriptional
      lacZ gene fusions was formed on a reporter shuttle vector using various DNA
      fragments from the bglP promoter region. Subsequent beta-galactosidase assays in
      S. mutans localized the bglP promoter region and identified putative -35 and -10
      promoter elements. Primer extension analysis identified the bglP transcriptional
      start site. In addition, a terminated bglP transcript formed by transcriptional
      termination was identified via transcript mapping experiments. CONCLUSION: The
      physical location of these genetic elements, the RAT site and the promoter
      regions, and the identification of a short terminated mRNA support the hypothesis
      that antitermination regulates the bglP transcript.

PMID- 16630358
TI  - Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for
      immunotherapy of systemic lupus erythematosus.
AB  - B cells play an important role in the pathogenesis of systemic lupus
      erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with
      the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An
      open-label, single-center study of 14 patients with moderately active SLE (total
      British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted.
      Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses
      with analgesic/antihistamine premedication (but no steroids) prior to each dose.
      Evaluations at 6, 10, 18 and 32 weeks (6 months post-treatment) follow-up
      included safety, SLE activity (BILAG score), blood levels of epratuzumab, B and T
      cells, immunoglobulins, and human anti-epratuzumab antibody (HAHA) titers. Total
      BILAG scores decreased by > or = 50% in all 14 patients at some point during the
      study (including 77% with a > or = 50% decrease at 6 weeks), with 92% having
      decreases of various amounts continuing to at least 18 weeks (where 38% showed a
      >/= 50% decrease). Almost all patients (93%) experienced improvements in at least
      one BILAG B- or C-level disease activity at 6, 10 and 18 weeks. Additionally, 3
      patients with multiple BILAG B involvement at baseline had completely resolved
      all B-level disease activities by 18 weeks. Epratuzumab was well tolerated, with
      a median infusion time of 32 minutes. Drug serum levels were measurable for at
      least 4 weeks post-treatment and detectable in most samples at 18 weeks. B cell
      levels decreased by an average of 35% at 18 weeks and remained depressed at 6
      months post-treatment. Changes in routine safety laboratory tests were infrequent
      and without any consistent pattern, and there was no evidence of immunogenicity
      or significant changes in T cells, immunoglobulins, or autoantibody levels. In
      patients with mild to moderate active lupus, 360 mg/m2 epratuzumab was well
      tolerated, with evidence of clinical improvement after the first infusion and
      durable clinical benefit across most body systems. As such, multicenter
      controlled studies are being conducted in broader patient populations.

PMID- 16630359
TI  - Arterial blood pressure monitoring in overweight critically ill patients:
      invasive or noninvasive?
AB  - INTRODUCTION: Blood pressure measurements frequently guide management in critical
      care. Direct readings, commonly from a major artery, are considered to be the
      gold standard. Because arterial cannulation is associated with risks, alternative
      noninvasive blood pressure (NIBP) measurements are routinely used. However, the
      accuracy of NIBP determinations in overweight patients in the outpatient setting
      is variable, and little is known about critically ill patients. This prospective,
      observational study was performed to compare direct intra-arterial blood pressure
      (IABP) with NIBP measurements obtained using auscultatory and oscillometric
      methods in overweight patients admitted to our medical intensive care unit.
      METHOD: Adult critically ill patients with a body mass index (BMI) of 25 kg/m2 or
      greater and a functional arterial line (assessed using the rapid flush test) were
      enrolled in the study. IABP measurements were compared with those obtained
      noninvasively. A calibrated aneroid manometer (auscultatory technique) with arm
      cuffs compatible with arm sizes and a NIBP monitor (oscillometric technique) were
      used for NIBP measurements. Agreement between methods was assessed using Bland
      Altman analysis. RESULTS: Fifty-four patients (23 males) with a mean (+/-
      standard error) age of 57 +/- 3 years were studied. The mean BMI was 34.0 +/- 1.4
      kg/m2. Mean arm circumference was 32 +/- 0.6 cm. IABP readings were obtained from
      the radial artery in all patients. Only eight patients were receiving vasoactive
      medications. Mean overall biases for the auscultatory and oscillometric
      techniques were 4.1 +/- 1.9 and -8.0 +/- 1.7 mmHg, respectively (P < 0.0001),
      with wide limits of agreement. The overestimation of blood pressure using the
      auscultatory technique was more important in patients with a BMI of 30 kg/m2 or
      greater. In hypertensive patients both NIBP methods underestimated blood pressure
      as determined using direct IABP measurement. CONCLUSION: Oscillometric blood
      pressure measurements underestimated IABP readings regardless of patient BMI.
      Auscultatory measurements were also inaccurate, tending to underestimate systolic
      blood pressure and overestimate mean arterial and diastolic blood pressure. NIBP
      can be inaccurate among overweight critically ill patients and lead to erroneous
      interpretations of blood pressure.

PMID- 16630360
TI  - The prognosis for individuals on disability retirement. An 18-year mortality
      follow-up study of 6887 men and women sampled from the general population.
AB  - BACKGROUND: Several studies have shown a markedly higher mortality rate among
      disability pensioners than among non-retired. Since most disability pensions are
      granted because of non-fatal diseases the reason for the increased mortality
      therefore remains largely unknown. The aim of this study was to evaluate
      potential explanatory factors. METHODS: Data from five longitudinal cohort
      studies in Sweden, including 6,887 men and women less than 65 years old at
      baseline were linked to disability pension data, hospital admission data, and
      mortality data from 1971 until 2001. Mortality odds ratios were analyzed with
      Poisson regression and Cox's proportional hazards regression models. RESULTS:
      1,683 (24.4%) subjects had a disability pension at baseline or received one
      during follow up. 525 (7.6%) subjects died during follow up. The subjects on
      disability pension had a higher mortality rate than the non-retired, the hazards
      ratio (HR) being 2.78 (95%CI 2.08-3.71) among women and 3.43 (95%CI 2.61-4.51)
      among men. HR was highest among individuals granted a disability pension at young
      ages (HR >7), and declined parallel to age at which the disability pension was
      granted. The higher mortality rate among the retired subjects was not explained
      by disability pension cause or underlying disease or differences in age, marital
      status, educational level, smoking habits or drug abuse. There was no significant
      association between reason for disability pension and cause of death. CONCLUSION:
      Subjects with a disability pension had increased mortality rates as compared with
      non-retired subjects, only modestly affected by adjustments for psycho-socio
      economic factors, underlying disease, etcetera. It is unlikely that these factors
      were the causes of the unfavorable outcome. Other factors must be at work.

PMID- 16630361
TI  - Membrane-associated heparan sulfate is not required for rAAV-2 infection of human
      respiratory epithelia.
AB  - BACKGROUND: Adeno-associated virus type 2 (AAV-2) attachment and internalization
      is thought to be mediated by host cell membrane-associated heparan sulfate
      proteoglycans (HSPG). Lack of HSPG on the apical membrane of respiratory
      epithelial cells has been identified as a reason for inefficient rAAV-2 infection
      in pulmonary applications in-vivo. The aim of this investigation was to determine
      the necessity of cell membrane HSPG for efficient infection by rAAV-2. RESULTS:
      Rates of transduction with rAAV2-CMV-EGFP3 in several different immortalized
      airway epithelial cell lines were determined at different multiplicities of
      infection (MOI) before and after removal of membrane HSPG by heparinase III.
      Removal of HSPG decreased the efficacy of infection with rAAV2 by only 30-35% at
      MOI < or = 100 for all of respiratory cell lines tested, and had even less effect
      at an MOI of 1000. Studies in mutant Chinese Hamster Ovary cell lines known to be
      completely deficient in surface HSPG also demonstrated only moderate effect of
      absence of HSPG on rAAV-2 infection efficacy. However, mutant CHO cells lacking
      all membrane proteoglycans demonstrated dramatic reduction in susceptibility to
      rAAV-2 infection, suggesting a role of membrane glycosaminoglycans other than
      HSPG in mediating rAAV-2 infection. CONCLUSION: Lack of cell membrane HSPG in
      pulmonary epithelia and other cell lines results in only moderate decrease in
      susceptibility to rAAV-2 infection, and this decrease may be less important at
      high MOIs. Other cell membrane glycosaminoglycans can play a role in permitting
      attachment and subsequent rAAV-2 internalization. Targeting alternative membrane
      glycosaminoglycans may aid in improving the efficacy of rAAV-2 for pulmonary
      applications.

PMID- 16630362
TI  - Three-dimensional drip infusion CT cholangiography in patients with suspected
      obstructive biliary disease: a retrospective analysis of feasibility and adverse
      reaction to contrast material.
AB  - BACKGROUND: Computed Tomography Cholangiography (CTC) is a fast and widely
      available alternative technique to visualise hepatobiliary disease in patients
      with an inconclusive ultrasound when MRI cannot be performed. The method has
      previously been relatively unknown and sparsely used, due to concerns about
      adverse reactions and about image quality in patients with impaired hepatic
      function and thus reduced contrast excretion. In this retrospective study, the
      feasibility and the frequency of adverse reactions of CTC when using a drip
      infusion scheme based on bilirubin levels were evaluated. METHODS: The medical
      records of patients who had undergone upper abdominal spiral CT with subsequent
      three-dimensional rendering of the biliary tract by means of CTC during seven
      years were retrospectively reviewed regarding serum bilirubin concentration,
      adverse reaction and presence of visible contrast media in the bile ducts at CT
      examination. In total, 153 consecutive examinations in 142 patients were
      reviewed. RESULTS: Contrast media was observed in the bile ducts at 144
      examinations. In 110 examinations, the infusion time had been recorded in the
      medical records. Among these, 42 examinations had an elevated bilirubin value
      (>19 micromol/L). There were nine patients without contrast excretion; 3 of which
      had a normal bilirubin value and 6 had an elevated value (25-133 micromol/L). Two
      of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor
      adverse reaction - a pricking sensation in the face. No other adverse effects
      were noted. CONCLUSION: We conclude that drip infusion CTC with an infusion rate
      of the biliary contrast agent iotroxate governed by the serum bilirubin value is
      a feasible and safe alternative to MRC in patients with and without impaired
      biliary excretion. In this retrospective study the feasibility and the frequency
      of adverse reactions when using a drip infusion scheme based on bilirubin levels
      has been evaluated.

PMID- 16630363
TI  - The training and development needs of nurses in Indonesia: paper 3 of 3.
AB  - BACKGROUND: Indonesia's recent economic and political history has left a legacy
      of widespread poverty and serious health problems, and has contributed to marked
      inequalities in health care. One means of responding to these challenges has been
      through a reconsideration of the professional roles of nurses, to enable them to
      deal with the range and complexity of health problems. However, there are
      currently a number of obstacles to achieving these aims: there is a serious
      shortfall in trained nurses; the majority of nurses have only limited education
      and preparation for the role; and there is no central registration of nurses,
      which means that it is impossible to regulate either the profession or the
      standards of care. This study aimed to establish the occupational profiles of
      each grade of nurse, identify their training and development needs and ascertain
      whether any differences existed between nurses working in different regions or
      within hospital or community settings. METHODS: An established and
      psychometrically valid questionnaire was administered to 524 nurses, covering
      three grades and coming from five provinces. RESULTS: Significant differences in
      job profile were found in nurses from different provinces, suggesting that the
      nature of the role is determined to some degree by the geographical location of
      practice. The roles of hospital and community nurses, and the different grades of
      nurse, were fairly similar. All nurses reported significant training needs for
      all 40 tasks, although these did not vary greatly between grade of nurse. The
      training needs of nurses from each of the provinces were quite distinct, while
      those of hospital nurses were greater than those of community nurses. CONCLUSION:
      The results suggest that the role of the nurse is not as diverse as might be
      expected, given the different levels of preparation and training and the
      diversity of their work environments. This may reflect the lack of a central
      registration system and quality framework, which would normally regulate clinical
      activities according to qualifications. The differences in training needs between
      subsections of the sample highlight the importance of identifying skills deficits
      and using this information to develop customized post-registration education
      programmes. Together, these results provide a rigorous and reliable approach to
      defining the occupational roles and continuing education needs of Indonesian
      nurses.

PMID- 16630364
TI  - Enhancing the comparability of costing methods: cross-country variability in the
      prices of non-traded inputs to health programmes.
AB  - BACKGROUND: National and international policy makers have been increasing their
      focus on developing strategies to enable poor countries achieve the millennium
      development goals. This requires information on the costs of different types of
      health interventions and the resources needed to scale them up, either singly or
      in combinations. Cost data also guides decisions about the most appropriate mix
      of interventions in different settings, in view of the increasing, but still
      limited, resources available to improve health. Many cost and cost-effectiveness
      studies include only the costs incurred at the point of delivery to
      beneficiaries, omitting those incurred at other levels of the system such as
      administration, media, training and overall management. The few studies that have
      measured them directly suggest that they can sometimes account for a substantial
      proportion of total costs, so that their omission can result in biased estimates
      of the resources needed to run a programme or the relative cost-effectiveness of
      different choices. However, prices of different inputs used in the production of
      health interventions can vary substantially within a country. Basing cost
      estimates on a single price observation runs the risk that the results are based
      on an outlier observation rather than the typical costs of the input. METHODS: We
      first explore the determinants of the observed variation in the prices of
      selected "non-traded" intermediate inputs to health programmes--printed matter
      and media advertising, and water and electricity--accounting for variation within
      and across countries. We then use the estimated relationship to impute average
      prices for countries where limited data are available with uncertainty intervals.
      RESULTS: Prices vary across countries with GDP per capita and a number of
      determinants of supply and demand. Media and printing were inelastic with respect
      to GDP per capita, with a positive correlation, while the utilities had a
      surprisingly negative relationship. All equations had relatively good fits with
      the data. CONCLUSION: While the preferred option is to derive costs from a random
      sample of prices in each setting, this option is often not available to analysts.
      In this case, we suggest that the approach described in this paper could
      represent a better option than basing policy recommendations on results that are
      built on the basis of a single, or a few, price observations.

PMID- 16630365
TI  - Stress analysis in a layered aortic arch model under pulsatile blood flow.
AB  - BACKGROUND: Many cardiovascular diseases, such as aortic dissection, frequently
      occur on the aortic arch and fluid-structure interactions play an important role
      in the cardiovascular system. Mechanical stress is crucial in the functioning of
      the cardiovascular system; therefore, stress analysis is a useful tool for
      understanding vascular pathophysiology. The present study is concerned with the
      stress distribution in a layered aortic arch model with interaction between
      pulsatile flow and the wall of the blood vessel. METHODS: A three-dimensional
      (3D) layered aortic arch model was constructed based on the aortic wall structure
      and arch shape. The complex mechanical interaction between pulsatile blood flow
      and wall dynamics in the aortic arch model was simulated by means of
      computational loose coupling fluid-structure interaction analyses. RESULTS: The
      results showed the variations of mechanical stress along the outer wall of the
      arch during the cardiac cycle. Variations of circumferential stress are very
      similar to variations of pressure. Composite stress in the aortic wall plane is
      high at the ascending portion of the arch and along the top of the arch, and is
      higher in the media than in the intima and adventitia across the wall thickness.
      CONCLUSION: Our analysis indicates that circumferential stress in the aortic wall
      is directly associated with blood pressure, supporting the clinical importance of
      blood pressure control. High stress in the aortic wall could be a risk factor in
      aortic dissections. Our numerical layered aortic model may prove useful for
      biomechanical analyses and for studying the pathogeneses of aortic dissection.

PMID- 16630366
TI  - Predicting caregiver assistance required for sit-to-stand following
      rehabilitation for acute stroke.
AB  - OBJECTIVE/METHODS: The objective of this case series was to determine the
      relationship between impairments identified at hospital admission and a reduced
      need for sit-to-stand (STS) assistance during an inpatient rehabilitation
      hospital stay. Fifty- five inpatients with a diagnosis of acute stroke were
      retrospectively studied. Demographic information and the following admission and
      discharge measures were collected from a chart review: bilateral dorsiflexion
      PROM, strength of the unaffected leg, Motricity Index (MI), presence of hemi
      neglect, gait velocity, and Functional Independence Measure (FIM) scores for STS,
      ambulation, and cognition. Sit to stand improvement was determined by a change of
      at least one Caregiver Assistance Level (CAL) in STS performance between hospital
      admission and discharge. CAL 1 = STS FIM score of 7 or 6; CAL 2 = STS FIM score
      of 5; CAL 3 = STS FIM score of 4, 3, 2, or 1. RESULTS: Unaffected knee extension
      strength, Motricity Index (MI) score, FIM cognition scores, and bilateral ankle
      dorsiflexion PROM were each univariate, age-adjusted predictors of improvement in
      STS CAL. A multivariate, 3 main-effect model that included admission FIM
      cognitive scores and ankle PROM correctly predicted 90.6% (48 out of 53) of the
      possible sit to stand improvement outcomes. Admission gait velocity and MI
      differentiated extent of functional change in those who improved. CONCLUSIONS:
      Cognition and bilateral ankle dorsiflexion PROM most strongly predicted STS CAL
      improvement during an inpatient rehabilitation stay. Caregivers of patients with
      significant impairments may benefit from early and intensive training on how to
      assist their family member in the STS task.

PMID- 16630367
TI  - Monitoring activity in individuals with Parkinson disease: a validity study.
AB  - This study was conducted to investigate the validity of an Activity Monitor (AM)
      recording functional activities in individuals with Parkinson disease (PD). A
      series of tasks were performed in both a fixed and a random manner by 11
      participants with PD (H & Y 2-3; age range 40-79 years). Participants, wearing an
      AM, were recorded for video analysis (VA). The strength of association (rs)
      between the AM and VA for duration of time in body positions, walking, and
      bicycling across both fixed and random modules ranged from 0.63 to 0.98, however,
      the AM reported significantly greater time spent in body positions in both
      modules. Kappa statistics (K) between the AM and VA were the highest for
      transitions in the fixed module with Ks ranging from 0.74 to 1.0. During the
      random module, the agreement between the AM and VA was lowest for transitions
      between sitting and standing. In general, the Ks were low for activities lasting
      less than 5 seconds. The data collected in the study support the conclusion that
      the AM accurately evaluated the duration of time spent in body positions, the
      number of transitions between body positions, and the duration of time spent
      walking for activities lasting longer than 5 seconds in individuals with PD.

PMID- 16630368
TI  - Taiji for individuals with Parkinson disease and their support partners: a
      program evaluation.
AB  - BACKGROUND AND PURPOSE: Exercise is advocated in the management of Parkinson
      disease (PD), however, little is known regarding the potential benefits of
      complementary mind/body exercise for this clinical population. The purpose of
      this pilot program evaluation was to gain insight into participant and instructor
      perceptions of the perceived benefits and potential utility of a taiji exercise
      program. PROGRAM EVALUATION: Program participants (N=15) included 8 individuals
      with PD and 7 support partners with no history of PD. Group taiji instruction was
      offered in 45-minute weekly sessions, for 12 weeks at a community facility. Post
      program evaluation included administration of a survey questionnaire, thematic
      analysis of a focus group discussion, instructor reflections, and review of
      attendance records. RESULTS: Benefits were perceived by participants in physical,
      psychological, and social domains. Thirteen of the survey respondents, including
      6 of the 8 respondents with PD reported perceiving a physical benefit attributed
      to taiji practice. Improved balance was reported most frequently. Instructor
      observations and participant testimony suggest movement capability for
      individuals with Parkinsons may also be improved by performing taiji. CONCLUSION:
      This preliminary research provides support for further Taiji Buddy program
      examination and application.

PMID- 16630369
TI  - Physical therapy during in-patient rehabilitation for a patient with Stiff-Person
      Syndrome.
AB  - BACKGROUND AND PURPOSE: Patients with Stiff-Person Syndrome (SPS) typically show
      stiffness and spasms, primarily of the trunk and proximal lower extremities. The
      purpose of this case report is to provide an overview of SPS and a description of
      the specific physical therapy management strategies used during a brief inpatient
      rehabilitation stay for a patient with SPS, illustrating the use of the
      patient/client management model in the Guide to Physical Therapist Practice. CASE
      DESCRIPTION: The patient was a 33-year-old with a 3- year history of SPS. He
      spent 10 days in an in-patient rehabilitation hospital where he received physical
      therapy daily. The initial examination revealed impairments of pain, range of
      motion, reflex integrity, and motor function, along with abnormalities of
      posture, balance, and function. The procedural interventions included therapeutic
      exercise and functional retraining. Stretching exercises were categorized
      according to their priority and level of difficulty to accommodate for the
      patient's varying symptoms, and relaxation exercises aimed to reduce the severity
      of the patient's spasms. The functional retraining program included transfer and
      progressive gait training. OUTCOMES: The patient showed improvements in ankle
      range of motion, posture, and gait (distance, speed, and independence), despite
      continued problems with stiffness, spasms, and pain. DISCUSSION: Physical
      therapists working with patients with SPS have challenges related to the paucity
      of information in the literature. The chronic, progressive, and variable nature
      of SPS indicates the need for life-long management, with the inclusion of an
      exercise program that can be adjusted accordingly, given the frequently changing
      symptoms experienced by the patient. As is shown with this case, it appears that
      physical therapy can improve function and some of the impairments associated with
      SPS.

PMID- 16630370
TI  - Gait, quality of life, and their association following total hip arthroplasty.
AB  - PURPOSE: Total hip arthroplasty (THA) surgery is one of the most common
      orthopedic procedures performed on individuals with end-stage osteoarthritis of
      the hip. This study: () compared temporal spatial gait parameters and quality of
      life (QOL) scores of individuals with unilateral total hip arthroplasty (THA) to
      those of healthy older adults ages 65 to 85 years and (2) explored the
      relationship between the variables. METHODS: Three dimensional motion analysis
      was used to calculate walking velocity, cadence, stride length, single support
      time, and double support time. All participants completed the Medical Outcome
      Survey Short Form 36 Health Survey (SF 36(R)) to measure health related QOL
      subscales. RESULTS: The individuals with THA walked slower (P = .005) with a
      longer double support phase (P = .02) and rated physical functioning (P < .0001 )
      and role physical scores (P = .001 ) lower than the healthy older adults. For all
      subjects combined, a positive correlation was identified between walking velocity
      and physical functioning (P = .001 ), role-physical scores (P = .001 ) and bodily
      pain (P = .001 ); a negative correlation was identified between double support
      time and role physical score (P = .002) and bodily pain (P =.002). CONCLUSION:
      Individuals who undergo THA surgery have gait deficits that relate to physical
      subscales of the SF36(R). These findings provide guidance for physical therapy
      interventions focused on gait performance after THA.

PMID- 16630371
TI  - Performance of balance impaired elders on three balance tests under two visual
      conditions.
AB  - PURPOSE: This study compared differences in balance measures among elderly adults
      with different degrees of balance impairments under different visual conditions.
      METHODS: This study was conducted on 89 adults (> 60 years) with balance
      impairments. Subjects were divided into 3 groups based on the initial Tinetti
      score: low risk of fall (LRF, n=29), moderate risk of fall (MRF, n=30) and high
      risk of fall (HRF, n=30). Three balance measures-Tinetti, Timed-up and Go (TUG),
      and Functional Reach-were tested with 2 different visual conditions: eyes open
      with normal vision (EONV) and eyes open with blurred vision (EOBV). All data were
      analyzed using repeated measures analysis of variance. RESULTS: Subjects with
      EOBV had significantly decreased Tinetti (P < .01 ) and Functional Reach (P < .01
      ) scores and increased TUG (P < .01 ) scores regardless of fall group. Subjects
      in the LRF group performed better in all 3 tests than those in MRF (P < .01 ) and
      HRF (P < .01 ) groups. Subjects in the MRF group performed better in all 3 tests
      than those in HRF (P < .01 ). There were significant interactions between vision
      and risk of falls in Tinetti (P < .01 ) and TUG (P < .01 ) scores. However, there
      was no significant interaction between vision and risk of falls in Functional
      Reach (P > .05) scores. CONCLUSION: Blurred vision significantly altered all 3
      balance measure scores in all risk groups. However, blurred vision had a greater
      influence on Tinetti and TUG scores than Functional Reach scores in subjects with
      higher risk of falls.

PMID- 16630372
TI  - Validity and reliability of measurements of elbow flexion strength obtained from
      older adults using elastic bands.
AB  - PURPOSE: This study determined the validity and reliability of measurements of
      elbow flexion strength obtained from older adults using elastic bands. METHODS:
      Forty-eight community-dwelling older adults with documented functional
      limitations completed 3 assessments of elbow flexion strength: a 30-second test
      using elastic bands to generate resistance, a similar test using dumbbells, and a
      test using an isokinetic dynamometer. One week later, subjects repeated the 30
      second elbow flexion test using elastic bands. RESULTS: The 30-second elbow
      flexion test using elastic bands was significantly correlated with both the 30
      second elbow flexion test using dumbbells (r = 0.62, P < 0.01 ) and the maximum
      isokinetic torque of the elbow flexors (r = 0.46, P < 0.01 ). The 30-second elbow
      flexion test using elastic bands demonstrated a high degree of test-retest
      reliability (intraclass correlation coefficient = 0.89, P < 0.01 ). CONCLUSION:
      The validity and reliability elbow flexion strength measured with elastic bands
      supports its use among functionally limited elders.

PMID- 16630373
TI  - Lateral rhythmic unipedal stepping in younger, middle-aged, and older adults.
AB  - PURPOSE: Voluntary and protective stepping performance changes with age. This has
      implications for the problem of falls in older adults. The purpose of this study
      was to examine the influence of metronome paced stepping practice on self
      selected preferred rhythmic unipedal stepping performance in the medial-lateral
      direction among younger, middle-aged and older adults. METHODS: Thirty-two
      healthy adult subjects (0 younger, 0 middle-aged, 2 older) participated. They
      performed rhythmic lateral stepping with their dominant limb at their preferred
      pace before and after 6 trials of metronome-paced stepping. RESULTS: Older
      subjects had longer stride periods than young and middle-aged subjects prior to
      metronome pacing. Older subjects exhibited a 25% decrease in preferred stride
      period between pre- and postpacing trials. This is compared to a 5% and 11 %
      decrease exhibited by middle-aged and younger subjects respectively. Preferred
      stride period was similar for older subjects as compared to younger and middle
      aged subjects after paced practice. Modification of the stride period occurred
      mainly during the stance phase of rhythmic stepping. CONCLUSIONS: Comparable
      stride periods across groups after pacing suggest stepping performance is
      modifiable. Brief intervals of paced stepping may offer older adults a short-term
      benefit to stepping performance.

PMID- 16630374
TI  - Effects of age and ACL reconstruction on quadriceps gamma loop function.
AB  - BACKGROUND AND PURPOSE: Both aging and anterior cruciate ligament (ACL)
      reconstruction are associated with strength deficits, which can in turn influence
      performance of activities of daily living. Thus it is informative to understand
      mechanisms underlying strength deficits. Age-related declines in strength follow
      reductions in muscle fiber numbers and size, whereas strength deficits following
      ACL reconstruction may be caused by the loss of intraligamentous
      mechanoreceptors. A common link between these conditions is the gamma spindle
      system, or the gamma loop. Appropriately applied vibration can affect the gamma
      loop by causing disruption of afferent feedback to a muscle and result in
      decreased force capabilities. We investigated the effect of age and ACL
      reconstruction on gamma loop function. METHODS: Maximal isometric strength (MVC)
      and electromyography (EMG) of the quadriceps were quantified before and after
      vibration stimulation of the infrapatellar tendon of 3 groups: young healthy
      (n=4; mean age=23.8 yrs), young ACL reconstructed (n=7; mean age=22.4 yrs), and
      older healthy (n=4; mean age=66.1 yrs) individuals. RESULTS: The quadriceps MVC,
      vastus lateralis EMG, vastus medialis EMG, and rectus femoris EMG declined
      significantly in the young healthy group following vibration stimulation to the
      infrapatellar tendon, which indicated an intact gamma loop. There were no changes
      in these variables for the old healthy and ACL reconstructed groups. CONCLUSION:
      Gamma loop function was impaired in both the older and ACL reconstructed groups
      possibly due to either decreased muscle spindle sensitivity or the loss of
      mechanoreceptors.

PMID- 16630375
TI  - Are scores on balance screening tests associated with mobility in older adults?
AB  - PURPOSE: To examine associations between measures of static and dynamic balance
      and performance of mobility tasks in older adults. METHODS: A cross-sectional
      analysis from 95 community dwelling participants (mean age 80.9 years, range 65 
      03 years). Participants performed tests of static (tandem stance) and dynamic
      (360 degrees turn) balance and mobility (walking speed and timed chair rise).
      Associations among balance and mobility measures were examined using correlation
      and logistic regression. RESULTS: Static and dynamic balance were moderately
      associated (r = -.462). Relationships between dynamic balance and mobility were
      stronger than those between static balance and mobility. The association between
      dynamic balance and walking speed was particularly strong (r = -.701 ). Using
      logistic regression, age, and balance performance were significant predictors for
      outcomes of walking speed (dichotomized to < .0 m/s, >/= .0 m/s), and timed chair
      rise (dichotomized to </= 3.6 s, > 3.6 s). Faster 360 degrees turn times were
      independently associated with faster walking speed and chair rise time.
      CONCLUSION: Mobility tasks require both dynamic and static balance. As falls are
      a major health risk for older adults, including brief assessments of dynamic and
      static balance in the examination of older adults provides valuable information
      about physical function and mobility.

PMID- 16630376
TI  - A global assessment of closed forests, deforestation and malaria risk.
AB  - Global environmental change is expected to affect profoundly the transmission of
      the parasites that cause human malaria. Amongst the anthropogenic drivers of
      change, deforestation is arguably the most conspicuous, and its rate is projected
      to increase in the coming decades. The canonical epidemiological understanding is
      that deforestation increases malaria risk in Africa and the Americas and
      diminishes it in South-east Asia. Partial support for this position is provided
      here, through a systematic review of the published literature on deforestation,
      malaria and the relevant vector bionomics. By using recently updated boundaries
      for the spatial limits of malaria and remotely-sensed estimates of tree cover, it
      has been possible to determine the population at risk of malaria in closed
      forest, at least for those malaria-endemic countries that lie within the main
      blocks of tropical forest. Closed forests within areas of malaria risk cover
      approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central
      Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South-east
      Asia. The corresponding human populations at risk of malaria within these forests
      total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By
      coupling these numbers with the country-specific rates of deforestation, it has
      been possible to rank malaria-endemic countries according to their potential for
      change in the population at risk of malaria, as the result of deforestation. The
      on-going research aimed at evaluating these relationships more quantitatively,
      through the Malaria Atlas Project (MAP), is highlighted.

PMID- 16630377
TI  - Predictors of the failure of treatment with trimethoprim-sulfamethoxazole in
      children with uncomplicated, Plasmodium falciparum malaria.
AB  - In many African countries, trimethoprim-sulfamethoxazole (TS) is recommended for
      the treatment of children with malaria and pneumonia - in accordance with the
      guidelines for the integrated management of childhood illness (IMCI) - and, in
      some settings, for the home management of febrile illnesses. There have been few
      studies, however, of the risk of failure of treatment with this drug combination
      in children with acute, Plasmodium falciparum malaria. The factors that identify
      children at risk of treatment failure after being given TS were therefore
      evaluated in 101 children with acute, symptomatic, uncomplicated, P. falciparum
      malaria, in a hyper-endemic area of south-western Nigeria. Overall, 11% of the
      children failed treatment by day 14. In a multivariate analysis, two factors were
      found to be independent predictors of the failure of treatment with TS: an age of
      <3 years (adjusted odds ratio=0.1; 95% confidence interval=0.02-0.53; P=0.007);
      and a body temperature of >or=38 degrees C 2 days after the commencement of
      treatment (adjusted odds ratio=4.9; 95% confidence interval=1.2-21.3; P=0.03).
      These findings may have implications for control efforts in some sub-Saharan
      African countries, where TS is recommended for the management of malaria in
      children, with or without pneumonia.

PMID- 16630378
TI  - Haptoglobin phenotype appears to affect the pathogenesis of American
      trypanosomiasis.
AB  - In Latin America, 16 million-18 million people are thought to be infected with
      Trypanosoma cruzi, the parasite that causes American trypanosomiasis. The
      pathophysiology of this disease, particularly that of its chronic phase, has yet
      to be fully elucidated. The major function of haptoglobin, an acute-phase plasma
      protein found in three different phenotypes (Hp1-1, Hp2-1 and Hp2-2), is to bind
      to free haemoglobin and so prevent the accumulation of reactive hydroxyl radicals
      and renal damage. The haptoglobin phenotype present can influence the severity
      and progression of many diseases, including infectious ones. The aim of the
      present study was to see if any haptoglobin phenotype could be associated with
      any of the various clinical forms of American trypanosomiasis, and so explore the
      possibility that haptoglobin and iron metabolism have a role in the
      pathophysiology of this disease. The Brazilian subjects investigated were either
      suffering from the 'indeterminate' (N=16), chronic cardiac (N=34), chronic
      digestive (N=13) or chronic 'combined' (i.e. cardiac plus digestive; N=29) forms
      of the disease or were apparently healthy blood donors from the same region as
      the patients (N=197). Haptoglobin phenotypes were determined by polyacrylamide
      gel electrophoresis. Among the iron-related parameters investigated in the
      patients, only total iron-binding capacity and the serum concentration of
      haptoglobin differed significantly with haptoglobin phenotype. Compared with its
      frequency in the healthy controls, the Hp2-2 phenotype was much more frequent in
      the patients with any form of American trypanosomiasis, in the patients with the
      indeterminate form of the disease, and in the patients with the chronic combined
      form (P<or=0.0001 for each). It therefore appears that, in terms of the
      pathogenesis in those exposed to T. cruzi, possession of the 2-2 phenotype of
      haptoglobin may be detrimental.

PMID- 16630379
TI  - Successful miltefosine treatment of post-kala-azar dermal leishmaniasis occurring
      during antiretroviral therapy.
AB  - The first two patients to be treated with miltefosine for post-kala-azar dermal
      leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had
      been treated with sodium stibogluconate, for relapsing visceral leishmaniasis
      (VL), four times between August 2002 and March 2004. In January 2004 this patient
      was found to be seropositive for HIV and began antiretroviral treatment with
      stavudine, lamivudine and nevirapine. Five months later he developed clinical
      PKDL, with extensive cutaneous, conjunctival and oral mucosal involvement. The
      second patient was a 42-year-old Ethiopian man who was treated for relapsing VL
      in November 2003. He too was subsequently found to be seropositive for HIV and
      was treated with stavudine, lamivudine and nevirapine from May 2004. He developed
      a nodular rash of PKDL over his face and upper body 2 weeks after starting the
      antiretroviral therapy. Treatment of both patients with oral miltefosine, at 100
      mg/day for 28 days, led to the complete regression of their PKDL lesions. When
      checked 3-6 months after the end of the miltesofine treatment, neither patient
      showed any signs of VL, PKDL or other HIV-associated disease.

PMID- 16630380
TI  - Rickettsiae of the spotted-fever group in ixodid ticks from Hungary:
      identification of a new genotype ('Candidatus Rickettsia kotlanii').
AB  - Three common European 'anthrophilic' ticks, Ixodes ricinus, Haemaphysalis
      concinna and Dermacentor reticulatus, were collected in Hungary and tested, in
      assays based on nested PCR, for rickettsiae of the spotted-fever group. Low
      percentages of I. ricinus (2.7%) and H. concinna (1.0%) and a high percentage of
      D. reticulatus (26.8%) were found to be infected. The rickettsiae in the ticks
      were then identified, by sequencing of the genes coding for 16S ribosomal RNA
      (16S rDNA), citrate synthase (gltA) and the rOmpA outer-membrane protein (ompA),
      as Rickettsia helvetica, Rickettsia monacensis, Rickettsia sp. RpA4, or what is
      probably a newly recognized Rickettsia species ('Candidatus Rickettsia
      kotlanii'). These results raise the possibility that rickettsiae other than
      Rickettsia slovaca are involved in human disease in Hungary. Current knowledge on
      the distributions of the rickettsiae of the spotted-fever group that are emerging
      in Europe is also summarized.

PMID- 16630381
TI  - The in-vitro antimicrobial activities of some medicinal plants from Cameroon.
AB  - The antimicrobial activities of 10 plant species (Voacanga africana, Crepis
      cameroonica, Plagiostyles africana, Crotalaria retusa, Mammea africana, Lophira
      lanceolata, Ochna afzelii, Ouratea elongata, Ou. flava and Ou. sulcata), each of
      which is currently used in the traditional medicine of Cameroon, were
      investigated in vitro. The activities of a methanol extract of each plant were
      tested, in disc-diffusion assays, against 37 reference or laboratory strains of
      seven species of microorganism (Staphylococcus aureus, S. epidermidis,
      Enterococcus hirae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginosa and Candida albicans). The minimal inhibitory concentrations of each
      extract were then estimated, against each of the more susceptible microorganisms
      (i.e. those giving an inhibition zone measuring at least 9 mm in diameter in the
      disc-diffusion assays), by agar dilution. Although, in the disc-diffusion assays,
      each of the 10 methanol extracts investigated displayed some degree of
      antimicrobial activity against at least one species of microorganism, no activity
      against the Gram-negative bacteria (Es. coli, K. pneumoniae and Ps. aeruginosa)
      was observed. The extract with the greatest antimicrobial activity was that of
      Pl. africana (Euphorbiaceae).

PMID- 16630382
TI  - Prevalences of Pneumocystis jiroveci, Mycobacterium tuberculosis and
      Streptococcus pneumoniae infection in children with severe pneumonia, in a
      tertiary referral hospital in northern Tanzania.
AB  - At the Kilimanjaro Christian Medical Centre, a tertiary referral hospital in
      northern Tanzania, both the number of paediatric cases of lower respiratory-tract
      infection (LRTI) and the associated mortality increased between 2000 and 2001.
      Molecular diagnostic tools were used to enhance the identification of the
      pathogens responsible for this perceived increase. All 72 children aged between 2
      and 60 months who were admitted with LRTI over a 3-month period were enrolled in
      the study. Induced sputum was collected from each child and, if the parents
      consented, the subjects were also tested for HIV. The sputum samples were each
      checked for bacteria by culture and, in amplification assays, for the DNA of
      Pneumocystis jiroveci, Mycobacterium tuberculosis and Streptococcus pneumoniae.
      Twenty-two (50%) of the 44 children tested for HIV had HIV-1 antibodies. Although
      only two children, both aged <6 months, were found PCR-positive for P. jiroveci,
      and only one was found positive for M. tuberculosis, 46 (including one of those
      found positive for P. jiroveci and the child found positive for M. tuberculosis)
      were found PCR-positive for S. pneumoniae. It therefore appears that most
      paediatric cases of LRTI who present at the hospital are attributable to S.
      pneumoniae, and that infections with this pathogen are entirely responsible for
      the observed increase in the incidence of LTRI in the local children. The
      increase seen in LRTI-associated mortality among the children may be the result
      of pneumococcal antibiotic resistance.

PMID- 16630383
TI  - Failure of twice-weekly iron supplementation to increase blood haemoglobin and
      serum ferritin concentrations: results of a randomized controlled trial.
AB  - In order to increase the intestinal absorption of iron whilst simultaneously
      minimising the side-effects and thus increasing compliance, once- or twice
      weekly, instead of daily, iron supplementation has been widely recommended. In a
      randomized, placebo-controlled, double-blind study in western Kenya, a tablet of
      ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo
      tablet was provided twice-weekly for 12 months to each child or adult
      investigated. At baseline each subject had a moderately low blood concentration
      of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were
      determined and each subject was tested for malarial and helminth infection and
      treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200
      children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12
      month study. At baseline, 47.5% of the children and 58.1% of the adults were
      anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was
      the most common helminth infection, and malaria was endemic. The results of
      bivariate analyses indicated that twice-weekly iron supplementation had no
      significant effect on blood Hb or SF concentrations, either in the children or
      the adults investigated. The results were confirmed in multiple linear-regression
      analyses, which revealed that the predictors of the final Hb concentration in the
      children investigated were age and infection, after enrollment, with Ascaris
      lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin
      (ACT) at final follow-up were predictors of the final SF concentration in the
      children. In adults, the predictors of the final Hb concentration were gender and
      HIV infection, and the predictors of the final SF concentration were age and the
      serum concentration of ACT at the final follow-up. Twice-weekly iron
      supplementation did not increase Hb or iron stores in children or adults. Since
      compliance appeared to be high, this lack of effect may be the result of an
      inadequate dose of iron or of subjects who have deficiencies in micronutrients
      other than iron.

PMID- 16630384
TI  - An inventory of the phlebotomine sandflies (Diptera: Psychodidae) found in the
      Turkish province of Konya.
AB  - Between the April and October of 1997, the sandflies in six areas (Centrum,
      Altinekin, Kadinhani, Cumra, Beysehir and Bozkir) of the Turkish province of
      Konya, in Central Anatolia, were surveyed. All the sandflies were caught close to
      houses, on sticky-paper traps placed in barns used by livestock. All 127
      specimens of Sergentomyia collected were either S. theodori (86.6%) or S. dentata
      (13.4%). The other 2017 sandflies caught represented 12 species of Phlebotomus -
      mostly P. papatasi (78.4%) or P. halepensis (10.9%), with P. sergenti (3.8%), P.
      simici (2.2%), P. kandelakii (1.6%), P. similis (0.9%), P. jacusieli (0.5%), P.
      neglectus (0.4%), P. transcaucasicus (0.3%), P. syriacus (0.3%), P. kyreniae
      (0.3%) and P. balcanicus (0.3%) relatively rare. Most (87%) of the flies were
      male. This represents the first report of P. transcaucasicus in Turkey. In
      addition, P. syriacus, P. neglectus, P. similis and S. dentata have not been
      detected before in Central Anatolia.

PMID- 16630385
TI  - A species-specific PCR for the identification of the malaria vector Anopheles
      bwambae.

PMID- 16630386
TI  - Pupal/demographic surveys to inform dengue-vector control.

PMID- 16630387
TI  - Sample sizes for identifying the key types of container occupied by dengue-vector
      pupae: the use of entropy in analyses of compositional data.
AB  - A method has been developed for estimating the sample sizes needed to identify
      categories that comprise a large proportion of a compositional data-set. The
      method is to be used in the design of surveys of mosquito pupae, for identifying
      the key container types from which the majority of adult dengue vectors emerge.
      Although a finite-population correction was devised for estimating the mean of a
      negative binomial distribution, other complications of parametric approaches make
      them unlikely to yield methods simple enough to be practically applicable. The
      Shannon-Wiener index was therefore investigated as a more useful alternative, at
      the cost of theoretical generalizability, in an approach based on re-sampling
      methods in conjunction with the use of entropy. This index can be used to
      summarize the degree to which pupae are either concentrated in a few container
      types, or dispersed among many. An empirical relationship between the index and
      the repeatability of surveys of differing sample sizes was observed. A step-wise
      rule, based on the entropy of the cumulative data, was devised for determining
      the sample size, in terms of the number of houses positive for pupae, at which a
      pupal survey might reasonably be stopped.

PMID- 16630388
TI  - Aedes aegypti pupal/demographic surveys in southern Mexico: consistency and
      practicality.
AB  - In interventions aimed at the control of the immature stages of Aedes aegypti
      (L.), the principal vector of the dengue viruses, attempts are often made to
      treat or manage all larval habitats in households. When there are resource
      constraints, however, a concentration of effort on the types of container that
      produce the most pupae may be required. Identification of these 'key' container
      types requires surveys of the immature stages and particularly - since these give
      the best estimates of the numbers of adults produced - of the numbers of pupae in
      local containers. Although there has been no clearly defined or standardized
      protocol for the sampling of Ae. aegypti pupae for many years, a methodology for
      'pupal/demographic' surveys, which may allow the risk of dengue outbreaks in a
      given setting to be estimated, has been recently described. The consistency and
      practicality of using such surveys has now been investigated in three cities in
      the Mexican state of Chiapas, Mexico. Using a combination of 'quadrat'- and
      transect-sampling methods, 600 houses in each city were each sampled twice.
      Containers within each study household were searched for pupae and larvae.
      Although 107,297 containers, belonging to 26 categories, were observed, only
      16,032 were found to contain water and 96% and 92% of these 'wet' containers
      contained no pupae and no third- or fourth-instar larvae, respectively. Although
      the random 'quadrat' sampling gave similar results to sampling along transects,
      there were statistically significant differences in the numbers of pupae
      according to container type and locality. The most important containers for pupal
      production were found to be large cement wash basins, which were present in
      almost every household investigated and from which 84% (10,257/12,271) of all
      pupae were collected. A focus on this class of container could serve as the basis
      of a targeted intervention strategy. When traditional Stegomyia indices were
      calculated they appeared to be correlated with the assessments of pupal
      abundance. The methodology for pupal/demographic surveys appears to be practical
      and to give consistent results, although it remains to be seen if monitoring of
      pupal productivity can adequately reflect the impact of vector-control
      interventions.

PMID- 16630389
TI  - Sample-size requirements for developing strategies, based on the
      pupal/demographic survey, for the targeted control of dengue.
AB  - Several methods to determine the sample size required for a reliable and
      practical assessment of the number of Aedes aegypti pupae in a community in
      Puerto Rico have been explored. Because the pupae were highly aggregated, the
      data were fitted to a negative binomial distribution. Classical statistical
      inference methods for sample-size determination demanded the sampling of >3,000
      premises for a reliable estimation of the mean number of pupae/person (with a 15%
      error). This number was reduced to 1,000-1,200 premises after applying a finite
      population correction. Database sub-sampling simulations, with increasing sample
      sizes, showed that the variability in the mean relative abundance of container
      types and in the mean number of pupae/container substantially decreased after
      sampling 186 and 310 premises, respectively. Sequential sampling was applied to
      test the hypotheses that the number of female pupae/person was at least 0.19
      (considered the dengue epidemic threshold) or no greater than 0.10 (arbitrarily
      set as the safe level). After sampling only 25 premises in the first survey and
      125 in the second, it was determined that the densities of female pupae were
      above the epidemic threshold. Thus, sequential sampling provided substantial
      reductions in the sample size required to determine if vector control was needed.
      Validation of the Ae. aegypti thresholds required for dengue transmission could
      confer viability and efficiency to dengue-vector surveillance and control
      programmes.

PMID- 16630390
TI  - Application of the pupal/demographic-survey methodology in an area of Havana,
      Cuba, with low densities of Aedes aegypti (L.).
AB  - Between the April and December of 2004, an Aedes aegypti (L.) pupal/demographic
      survey was conducted in the Playa municipality of Havana. The aims were to
      identify the key types of container in the production of the adult mosquitoes
      (and so provide a basis for targeted control) and assess transmission risk in
      terms of the number of pupae/person. Pupal abundance, as measured in the survey,
      was compared with traditional Stegomyia indices. The immature stages of Ae.
      aegypti were only found in 70 of the 15,153 containers that were investigated and
      the pupae of this species were only seen in 52 of the containers. Ground-level
      water-storage tanks yielded 74.1% of all the pupae, with a further 19.0% found in
      miscellaneous small containers. The utility of the pupal/demographic-survey
      methodology in the evaluation of dengue risk in the study area, and other areas
      of Cuba with low densities of Ae. aegypti, is discussed.

PMID- 16630391
TI  - Use of the pupal/demographic-survey technique to identify the epidemiologically
      important types of containers producing Aedes aegypti (L.) in a dengue-endemic
      area of Venezuela.
AB  - As dengue continues to emerge as a major public-health problem world-wide,
      efforts to control the dengue vector Aedes aegypti must become more effective and
      efficient. Results from larval and pupal surveys applied in Venezuela illustrate
      the uniqueness of the information gained from pupal surveys; information that is
      lost when traditional Stegomyia indices are calculated. As most Ae. aegypti pupae
      will emerge to become adults, controlling the containers that produce the most
      pupae could have the greatest impact on the adult population. Pupal-survey
      results in Venezuela showed that large (150- to 200-litre) water drums produce
      the greatest number of pupae throughout the year. In the rainy season,
      approximately 70% of all pupae are found in these drums or in tyres, buckets and
      tanks. Over 80% of pupae in the dry season are found in drums and tanks alone. By
      targeting only those domestic breeding containers that produce the greatest
      number of pupae, control efforts may be streamlined to have the greatest impact
      on reducing the local adult Ae. aegypti population.

PMID- 16630392
TI  - Application of the pupal/demographic-survey methodology to identify the key
      container habitats of Aedes aegypti (L.) in Malindi district, Kenya.
AB  - The pupal/demographic-survey methodology was evaluated in three coastal areas
      (one urban, one peri-urban and one rural) of Malindi district, Kenya, in attempts
      to identify the types of domestic container that are most productive for Aedes
      aegypti (L.) pupae. The results demonstrated the practicality and consistency of
      the methodology, as a tool both for identifying and guiding the targeted control
      of the most productive container habitats, and for determining the mean numbers
      of pupae/person, as measures of the risk of dengue transmission.Twenty-five types
      of container were identified indoors and 50 types outdoors. In total, only 4,178
      pupae were seen indoors and 795 outdoors. Pupal productivity was dependent on the
      type, location and volume of the container and the season of the year. Metallic
      drums and jerricans contributed >70% of the pupae encountered indoors in the wet
      season whereas, in the rural area, plastic drums contributed 83.7% of all the
      larvae seen outdoors during the dry season. Container productivity was not
      consistent during the different surveys. The highest mean numbers of pupae/person
      (7.61) and of pupae/household (18.12) were recorded in the rural area.

PMID- 16630393
TI  - Aedes aegypti (Diptera: Culicidae) production from non-residential sites in the
      Amazonian city of Iquitos, Peru.
AB  - Programmes for the surveillance of Aedes aegypti (L.) often focus on residential
      areas, ignoring non-residential sites. Between November 2003 and October 2004,
      pupal/demographic surveys were therefore conducted in non-residential sites in
      the Peruvian city of Iquitos. The sampled sites included schools, factories,
      ports, public markets, petrol stations, commercial zones, airports, government
      buildings, animal-production areas, and recreational areas. Compared with the
      residential sites that had been surveyed a few years earlier, the non-residential
      sites generally had fewer pupae/ha, even though pupae were found in a high
      percentage of the sites investigated. Nonetheless, although <56 pupae/ha were
      observed in the industrial, commercial, recreational and school sites, the river
      boats in the ports and the areas in and around public markets sometimes had pupal
      abundances (of 122-213 pupae/ha) that were comparable with those previously
      recorded in the residential sites. When the relative production of Ae. aegypti
      was calculated by container type and characteristic (lidded/lidless,
      indoors/outdoors, and water-use patterns), no single container category was found
      to be a major producer of Ae. aegypti, with the exception of flower vases in
      cemeteries. In general, almost all (97%) of the pupae collected in the non
      residential sites came from unlidded containers, although 91% of those collected
      in river boats came from lidded storage areas. With the exception of lumber
      mills, plant nurseries and markets (where only 39%-60% of the pupae were
      collected outdoors), >70% of pupal production was outdoors. In commercial areas,
      41% of the pupae came from manually-filled containers, compared with <12% in
      residential sites. These results indicate that non-residential sites can be
      highly productive for Ae. aegypti and that the role of such sites in dengue
      transmission requires further investigation.

PMID- 16630394
TI  - Pupal-productivity surveys to identify the key container habitats of Aedes
      aegypti (L.) in Barranquilla, the principal seaport of Colombia.
AB  - Surveys were conducted in three neighbourhoods of Barranquilla, the main seaport
      of Colombia, to identify, using counts of pupae in water containers during the
      wet and dry seasons, the most productive Aedes aegypti breeding sites. Overall,
      3,433 premises were investigated in the wet season and 3,563 in the dry,
      representing, respectively, 82.3% and 84.6% of the total numbers of premises in
      the study areas. Despite a reasonably reliable supply of piped water, there were
      still some large storage containers for domestic water (cement ground tanks and
      plastic, metal and cement drums) in the area. Although such containers
      represented only 1.8%-16.3% of the total number of containers observed, they
      contributed 72.0%-78.2% and 65.0%-95.8% of the total Ae. aegypti pupal population
      in the three study neighbourhoods during the wet and dry seasons, respectively.
      In contrast, bottles represented 23.0%-88.9% of the total number of containers
      but produced no more than 0.1% of the total Ae aegypti pupal populations in these
      neighbourhoods. Other containers (tyres, vases, 'other discarded' and 'other
      used') generally produced only low numbers of pupae. In some settings, however,
      containers in the 'other discarded' category could contribute up to 19% of the
      total pupal population, and in one survey of one neighbourhood a single container
      in this category held 9.1% of all the pupae collected. These results, from a city
      where dengue fever is endemic, will help to focus local campaigns for Ae. aegypti
      source-reduction on the most productive categories of container.

PMID- 16630395
TI  - Dengue research and training supported through the World Health Organization.
AB  - The rapidly increasing burden of dengue, the varied and often poorly understood
      factors contributing to its global spread, and the challenges of preventing and
      controlling it have led to a renewed call for more research and training on the
      disease. The main aims are to improve vector control, case management, and
      primary prevention through vaccine development. The World Health Organization
      (WHO), through its inter-departmental working group on dengue, is actively
      engaged in supporting and co-ordinating the major research activities. The dengue
      research initiatives of the Special Programme for Research and Training in
      Tropical Diseases (TDR), other departments at the WHO's Geneva headquarters, the
      WHO's regional and country offices, and the organization's dengue-affected member
      states are summarized in this article. This intensified effort, in close
      collaboration with other stakeholders, is contributing towards the goals of
      reversing the current epidemiological trends and of reducing the global burden
      posed by dengue in all of its forms.

PMID- 16630396
TI  - Novel agents in acute myeloid leukemia.
AB  - In the past 40 years, advances in supportive care and development of
      chemotherapeutic agents have led to improved outcomes in patients with acute
      myeloid leukemia. High relapse rates following remission have led to extensive
      efforts to develop techniques and regimens for detecting and eliminating minimal
      residual disease. However, the best postremission therapy has not been
      identified. Better understanding of the biology and the molecular pathogenesis of
      AML has led to the development of new, more specific agents and strategies for
      AML treatment. Targeted therapy has improved outcomes in some patients. Most of
      the new agents are less toxic then their predecessors, and they can be used in
      combination with the more intensive traditional regimens.

PMID- 16630397
TI  - Chest wall relapse after mastectomy for ductal carcinoma in situ: a report of 10
      cases with a review of the literature.
AB  - Local chest wall relapse following mastectomy for ductal carcinoma in situ (DCIS)
      is an unusual event. We report on 10 cases of patients treated with mastectomy
      for DCIS who subsequently experienced a chest wall relapse as the first site of
      recurrence. To our knowledge, this is the largest reported collection of
      postmastectomy chest wall relapses for DCIS. The tumor registry and medical
      records from Yale-New Haven Hospital of all patients treated for ductal carcinoma
      in situ were reviewed. Individual records and radiation therapy charts of those
      patients sustaining a chest wall relapse following mastectomy were reviewed in
      detail. All pathology from the original mastectomy, as well as from the chest
      wall relapse, was re-reviewed by the pathologist. All chest wall relapses were
      treated with radiation therapy, with or without adjuvant systemic therapy. Of the
      10 cases, 9 patients remain alive without evidence of disease. Young patient age,
      multiquadrant disease, and the presence of residual normal breast tissue were
      common features among these chest wall relapses. Pathological features of the
      original mastectomies and chest wall relapses are presented and discussed.
      Postmastectomy chest wall relapses in patients with DCIS are an uncommon event.
      Patients treated aggressively with resection of the lesion followed by radiation
      therapy to the chest wall have a favorable prognosis.

PMID- 16630398
TI  - The role of radiation therapy in intrahepatic cholangiocarcinoma.

PMID- 16630399
TI  - Maybe one drug does not fit all.

PMID- 16630400
TI  - NSAIDs and prostate cancer risk.

PMID- 16630401
TI  - Canstatin: an inhibitor of angiogenesis and tumor growth revisited.

PMID- 16630402
TI  - Consideration of the role of radiotherapy for unresectable intrahepatic
      cholangiocarcinoma: a retrospective analysis of 75 patients.
AB  - The role of radiotherapy in the treatment of intrahepatic cholangiocarcinoma is
      controversial. We undertook this study to determine if radiotherapy is
      appropriate for patients with unresectable or lymph node metastatic intrahepatic
      cholangiocarcinoma. METHODS AND MATERIALS: The records of 75 patients with
      intrahepatic cholangiocarcinoma were reviewed and analyzed by Kaplan-Meier method
      and Cox proportional hazards analysis. Thirty-eight patients who received limited
      local external-beam radiotherapy were classified as the radiotherapy group. This
      group included nine patients with resected intrahepatic cholangiocarcinoma with
      macroscopic residual lymph nodes receiving postoperative external-beam
      radiotherapy, seven patients with postoperative recurrences in lymph nodes
      receiving external-beam radiotherapy for salvage failure after treatment with
      surgery alone, and 22 patients with unresectable intrahepatic cholangiocarcinoma.
      The median total dose was 50 Gy (range, 30-60 Gy) in daily doses of 2
      Gy/fraction, five times a week. Thirty-seven patients with intrahepatic
      cholangiocarcinoma (including 14 with resectable disease and synchronous or
      asynchronous lymph node metastases, and 23 with unresectable disease) who did not
      receive external-beam radiotherapy were selected from hospitalized patients in
      the same period and were classified as the nonexternal-beam radiotherapy group.
      Parameters observed included survival rates and tumor response to external-beam
      radiotherapy demonstrated both by clinical symptoms and by computed tomography
      scan/magnetic resonance image. RESULTS: Objective responses to external-beam
      radiotherapy were 36.4% for intrahepatic tumors in 22 patients with unresectable
      intrahepatic cholangiocarcinoma, and 52% for lymph node metastases in 25 patients
      with resectable or unresectable intrahepatic cholangiocarcinoma. Pain was
      relieved in 90% of the patients who received external-beam radiotherapy. The
      survival rates at 1 and 2 years for patients with unresectable intrahepatic
      cholangiocarcinoma treated with external-beam radiotherapy (n = 22) compared with
      those who did not receive external-beam radiotherapy (n = 23) were 36.1% versus
      19.0% and 5.2% versus 4.7%, respectively (log-rank P = 0.021). The survival
      experience of the 16 patients with lymph node metastases (synchronous or
      asynchronous) who underwent hepatectomy combined with external-beam radiotherapy
      was superior to that of the group (n = 14) who did not receive external-beam
      radiotherapy (median survival, 468 and 211 days, respectively; log-rank P =
      0.075). These results show that external-beam radiotherapy influenced the
      survival in the patients with unresectable intrahepatic cholangiocarcinoma or
      lymph node metastases. The most common reason for death was liver failure caused
      by uncontrolled intrahepatic disease. Grade 3 toxicity in the external-beam
      radiotherapy group was infrequent. CONCLUSION: External-beam radiotherapy seems
      to improve the prognosis of patients with unresectable intrahepatic
      cholangiocarcinoma and deserves further study.

PMID- 16630403
TI  - Postoperative concurrent chemoradiotherapy with mitomycin in advanced squamous
      cell carcinoma of the head and neck: results from three prospective randomized
      trials.
AB  - Recent prospective randomized trials have shown concurrent chemoradiotherapy
      improves locoregional control in postoperative patients with squamous cell
      carcinoma of the head and neck using cisplatin-based regimes. This report
      presents data pooled from three randomized trials employing mitomycin, selecting
      those patients treated postoperatively, to evaluate the long-term benefit of
      mitomycin in the postoperative setting and to compare these results with those of
      two other recently published randomized trials. METHODS AND MATERIALS: Between
      1980 and 1999, a total of 331 patients with squamous cell carcinoma of the head
      and neck from the three prospective trials were enrolled. Of the 205
      postoperative patients in these trials, 103 were randomized to receive mitomycin
      and radiation, while 102 received radiation alone or radiation with porfiromycin
      in the third trial. Patients were treated with standard daily radiotherapy to a
      total median dose of 60 Gy over 47 days. Patients who were randomized to
      mitomycin C received 15 mg/m2 of the drug on days 5 and 47 (or last day).
      RESULTS: The 5-year rate of locoregional control was higher in the mitomycin
      arms. There was no statistically significant difference in the rates of overall
      survival or distant metastasis. Patients had a lower percentage of high-risk
      factors in both arms of the study, compared with patients in the large
      prospective trials, including positive margins, two or more positive lymph nodes,
      or oropharynx primary tumors. The gains in locoregional control realized with
      mitomycin were similar to the improvements in the recently published randomized
      trials using platinum. CONCLUSIONS: These results confirm significant gains in
      locoregional control using concurrent chemoradiotherapy in the postoperative
      setting for patients with squamous cell carcinoma of the head and neck. The lack
      of consensus over a benefit in the rates of overall survival and distant
      metastasis emphasizes the need for further prospective trials in the
      postoperative management of squamous cell carcinoma of the head and neck.

PMID- 16630404
TI  - Association between nonsteroidal anti-inflammatory drugs and prostate cancer
      occurrence.
AB  - Prostate cancer is the most common malignancy among men in Western nations.
      Previous studies indicate that nonsteroidal anti-inflammatory drugs have an
      inhibitory effect on prostate cancer cells. We evaluated the association between
      frequent use of nonsteroidal anti-inflammatory drugs and prostate cancer
      occurrence. METHODS: We conducted a nested case-control study using medical
      administrative databases. All men older than 65 years of age who had filled at
      least one prescription for nonselective nonsteroidal anti-inflammatory drugs,
      cyclooxygenase-2 inhibitors (coxibs), aspirin, or acetaminophen between January
      1999 and December 2002 were eligible. Among this group, we identified men who
      underwent prostate biopsy between January 2000 and June 2002 and did not have a
      diagnosis of any cancer in the preceding 2-year period. Cases were those with a
      diagnosis of prostate cancer. Controls were those who did not receive a diagnosis
      of any cancer. Logistic regression models were used to determine associations
      between prostate cancer occurrence and frequent exposure (more than 4 months) to
      nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors or aspirin
      during the prior 2 years in comparison with no exposure to any of these drugs,
      adjusting for age and prior finasteride use. RESULTS: We identified 2025 cases
      and 2150 controls. Older men were at greater risk for developing prostate cancer.
      Exposure to nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors was
      associated with a reduced likelihood of prostate cancer (odds ratio [OR], 0.71;
      95% confidence interval [CI], 0.58-0.86) as was exposure to aspirin (OR, 0.84;
      95% CI, 0.74-0.96). DISCUSSION: Our results suggest that among men 65 years of
      age or older, frequent use of nonsteroidal anti-inflammatory drugs/cyclooxygenase
      2 inhibitors and use of aspirin are associated with a reduced risk of prostate
      cancer.

PMID- 16630405
TI  - Enhancement of antiangiogenic effects of human canstatin with a hypoxia-regulated
      transgene vector in lung cancer model.
AB  - Canstatin, a newly identified antiangiogenesis protein, has a potent inhibitory
      effect on the proliferation and growth of endothelial cells. To enhance the
      expression and antiangiogenic effects of canstatin in solid tumors, we
      constructed a eukaryotic expression vector that encodes human canstatin cDNA
      downstream from nine copies of the hypoxia-response element. METHODS: Canstatin
      complementary DNA from adult liver tissues was cloned into the mammalian
      expression vector pCMV-Script. Nine copies of the hypoxia-response element were
      ligated upstream from the canstatin gene near the cytomegalovirus promoter. The
      recombinant vector, pCMV9Cans, was transformed into A549 cells by cationic
      liposomes. The transformed cells were cultured under oxic and anoxic conditions.
      We detected canstatin messenger ribonucleic acid and protein expression in
      transformed cells by TaqMan polymerase chain reaction and Western blot analysis,
      respectively. Human umbilical vein endothelial cells were cocultured with
      recombinant vector transformed A549 cells using Transwell plates under oxic and
      anoxic conditions. The proliferation and apoptosis of the cocultured endothelial
      cells were evaluated with 3H-thymidine incorporation and terminal
      deoxynucleotidyl-mediated biotinylated deoxyuridine triphosphate nick end
      labeling methods (TUNEL), respectively. A canstatin-encoding vector with no
      hypoxia-response element, pCMVCans, was used as the positive control, and naked
      plasmid-transformed and singly cultured parental cells were used as negative
      controls. The biologic activity of the vector in tumor tissues of lung cancer
      bearing nude mice was evaluated by microvessel counts. Canstatin protein
      expression was assessed by Western blot analysis in tumor tissues. pCMVCans and
      empty vector were used as controls in the in vivo assays. RESULTS: Canstatin
      messenger RNA and protein were detected in both pCMV9Cans- and pCMVCans
      transformed A549 clones. Under oxic conditions, canstatin expression was not
      significantly different in clones stably transformed with pCMV9Cans or pCMVCans.
      However, under anoxic conditions canstatin expression was significantly higher in
      pCMV9Cans-transformed cells than in pCMVCans-transformed cells. Moreover, the 3H
      thymidine uptake rate of the human umbilical vein endothelial cells was markedly
      lower than that of the pCMVCans-transformed cells, and many endothelial cells
      underwent apoptosis when cocultured with pCMV9Cans-transformed A549 cells,
      especially under anoxic conditions. We detected canstatin expression in tumor
      tissues; the expression level in pCMV9Cans-transformed tumors was significantly
      higher than that in pCMVCans-transformed tumors. An in vivo assay showed that
      tumors transformed with pCMV9Cans remained small, and microvessels in those
      tumors were much fewer than those in pCMVCans-transformed tumors. CONCLUSION: The
      hypoxia-regulated vector pCMV9Cans increases the expression of canstatin, thereby
      enhancing its biological effects. We believe that the hypoxia-inducible canstatin
      expressing vector is a promising gene therapy tool for antiangiogenesis research.

PMID- 16630406
TI  - Treatment of nasopharyngeal carcinoma in the modern era: analysis of outcomes and
      toxicity from a single center in a nonendemic area.
AB  - We analyzed treatment outcomes for nasopharyngeal carcinoma in a single
      institute. MATERIALS AND METHODS: From 1992 to 2002, 82 patients with
      nasopharyngeal cancer were treated. Kaplan-Meier estimates of overall and disease
      free survival were calculated. The log-rank test was used to determine
      significant prognostic determinants of overall and disease-free survival.
      RESULTS: Patients received one of three regimens: radiotherapy alone (n = 19),
      radiotherapy with concurrent carboplatin (n = 46), or radiotherapy with
      concurrent cisplatin (n = 17). Fifty-seven percent of patients had their
      radiotherapy planned using fluoroscopy-based methods. Overall, 93.9% of patients
      received all prescribed radiotherapy. Response rate to treatment was 98.7%. Three
      year disease-free survival and overall survival rates for all patients were 69.0%
      and 65%, respectively. Five patients had late grade 3-4 toxicities. There were no
      treatment-related deaths. Twenty-four percent of patients were hospitalized
      during treatment, and 72.6% lost < or = 9.9% of pretreatment weight. Forty-two
      percent of failures were local and 27.3% were distant. Ninety percent of deaths
      were nasopharyngeal carcinoma-related. Disease stage was the only significant
      predictor of overall survival. DISCUSSION: At our center, treatments given for
      nasopharyngeal carcinoma from 1992 to 2002 had acceptable toxicity rates. Further
      follow-up of patients treated with modern radiotherapy planning methods and
      chemotherapy regimens is needed to compare our institutional results with other
      published outcomes with more validity.

PMID- 16630407
TI  - Fractionated proton radiation treatment for pediatric craniopharyngioma:
      preliminary report.
AB  - This retrospective preliminary review evaluated the efficacy and toxicity of
      fractionated proton radiotherapy in the management of pediatric
      craniopharyngioma. METHODS: Sixteen patients, aged 7-34 years, were treated with
      proton-beam radiation. All had undergone at least one tumor resection. Seven
      patients underwent repeat resection for recurrence; one had previous x-ray
      radiotherapy. A daily dose of 1.8 cobalt gray equivalent was used to give a total
      dose in the range of 50.4-59.4 cobalt gray equivalent. RESULTS: Local control was
      achieved in 14 of 15 patients. Twelve of 15 patients survived. There were few
      acute side effects. Long-term complications included newly diagnosed
      panhypopituitarism, a cerebrovascular accident from which the patient fully
      recovered, and an out-of-proton-field meningioma in the single patient who
      received previous radiotherapy. DISCUSSION: Fractionated proton radiotherapy is
      an effective treatment for children with craniopharyngioma. Longer follow-up is
      needed to evaluate late complications.

PMID- 16630408
TI  - DHEA-induced antiproliferative effect in MCF-7 cells is androgen- and estrogen
      receptor-independent.
AB  - Dehydroepiandrosterone, an adrenal hormone derived from cholesterol, can be
      metabolized to estrogens (estradiol) and androgens (testosterone). In this study,
      we evaluated whether the antiproliferative effect induced by
      dehydroepiandrosterone in MCF-7 cells (an estrogen-dependent breast cancer cell
      line) is direct, or indirect, through its conversion to estradiol or
      testosterone. Although dehydroepiandrosterone had an antiproliferative effect at
      supraphysiologic concentrations, when it was used at physiologic concentrations,
      it increased the proliferation of MCF-7 cells. 17Beta-estradiol induced an
      increase in MCF-7 cell proliferation at physiologic concentrations, whereas
      testosterone had a weak inhibitory effect at 100 microM. Dehydroepiandrosterone
      sulfate (its inactive sulfate ester) had no effect upon the cell cycle.
      Dehydroepiandrosterone-induced antiproliferative and proliferative effects were
      not blocked by inhibitors of androgen or estrogen receptors, thus indicating that
      its effect is secondary to a direct interaction with a "putative" receptor rather
      than a conversion into steroid hormones. These results suggest that
      dehydroepiandrosterone could be used at supraphysiologic concentrations in the
      treatment of breast cancer.

PMID- 16630409
TI  - Retinal complications of cataract surgery.
AB  - Cataract surgery, like any surgical procedure, has associated complications.
      Acute retinal complications include globe perforation, dislocated lens fragments,
      hemorrhagic choroidal detachment, and endophthalmitis. Late retinal complications
      include retinal detachment, cystoid macular edema, and exacerbation of diabetic
      retinopathy and other retinal conditions. Proper and timely management of retinal
      complications from cataract surgery is crucial in maximizing visual outcomes.
      Many of the complications and current management strategies will be outlined in
      this review.

PMID- 16630410
TI  - Comments on: Retinal complications of cataract surgery.

PMID- 16630411
TI  - Management of retinal breaks and conditions predisposing to retinal detachment.
AB  - This update discusses the available evidence and provides recommendations
      regarding when to observe and when and how to treat prophylactically retinal
      breaks in eyes. These recommendations include eyes with conditions predisposing
      to rhegmatogenous retinal detachment, such as those with retinal degeneration,
      aphakia, fellow eyes of a rhegmatogenous retinal detachment, or eyes of patients
      with inherited vitreoretinopathies.

PMID- 16630412
TI  - Comments on: Management of retinal breaks and conditions predisposing to retinal
      detachment.

PMID- 16630413
TI  - The Internet's role in patient/physician interaction: bringing our understanding
      in line with online reality.
AB  - The Internet has changed the way medical practitioners communicate and educate
      themselves and their patients. The Internet has provided enormous opportunity,
      but it has also led to complexity and uncertainty. We hope patients are
      intelligent partners in the management of their health, and we invite them to
      engage in the process of this management. Managed care has forced us to limit the
      length, depth, and frequency of patient encounters. Hopefully, patients will
      become more literate concerning their own conditions and their own bodies. They
      may lack medical knowledge and language. As a result, they may be drawn to online
      resources. Physicians often get angry or irritated when patients seek and
      retrieve information on their own. Our attempts to mediate patients' online
      activities can stress the patient/physician relationship. This could lead to
      misunderstandings, miscommunications, and fray an already fragile trust. There
      are many issues that accompany this cultural shift. We need to acknowledge the
      problem in order to achieve a resolution that is mutually satisfactory.

PMID- 16630414
TI  - Risk of cataracts and glaucoma with inhaled steroid use in children.
AB  - With the increasing use of inhaled corticosteroids as first-line therapy in the
      treatment of asthma, the adverse effects of these preparations have become the
      topic of much research in recent years. While it is known that orally
      administered steroids can have metabolic, musculoskeletal, dermatologic,
      hematologic, and ophthalmologic effects (inhaled corticosteroids have minimal
      reported hematologic or musculoskeletal effects, but have some effects on
      metabolic processes such as calcium metabolism), it is less understood whether or
      not, and at what doses, inhaled corticosteroids will effect the eye. A
      computerized literature search was performed to search for literature pertaining
      to the specific use of oral or inhaled (nasal or bronchial) steroids, adverse
      effects, side effects, long-term use, chronic use, glaucoma, ocular effects, and
      increased ocular pressure. The search focused on the effects of inhaled
      corticosteroids in both adults and children, but contained an emphasis on
      children; studies pertaining to the effects in children, however, are limited.

PMID- 16630416
TI  - Sudden loss of vision in a middle-aged woman.

PMID- 16630417
TI  - Flattery.

PMID- 16630418
TI  - Does flattery work? A comparison of 2 different cover letters for an
      international survey of orthopedic surgeons.
AB  - BACKGROUND: Surveys are an important tool for gaining information about
      physicians' beliefs, practice patterns and knowledge. However, the validity of
      surveys among physicians is often threatened by low response rates. We
      investigated whether response rates to an international survey could be increased
      using a more personalized cover letter. METHODS: We conducted an international
      survey of the 442 surgeon-members of the Orthopaedic Trauma Association on the
      treatment of femoral-neck fractures. We used previous literature, key informants
      and focus groups in developing the self-administered 8-page questionnaire. Half
      of the participants received the survey by mail, and half received an e-mail
      invitation to participate on the Internet. We alternately allocated participants
      to receive a "standard" or "test" cover letter. RESULTS: We found a higher
      primary response rate to the test cover letter (47%) than to the standard cover
      letter (30%) among those who received the questionnaire by mail. There was no
      difference between the response rates to the test and to the standard cover
      letters in the Internet group (22% v. 23%). Overall, there was a higher primary
      response rate for the test cover letter (34%) when both the mail and Internet
      groups were combined, compared with the standard cover letter (27%). CONCLUSIONS:
      Our test cover letter to surgeons in our survey resulted in a significantly
      higher primary response rate than a standard cover letter when the survey was
      sent by mail. Researchers should consider using a more personalized cover letter
      with a postal survey to increase response rates.

PMID- 16630419
TI  - Clinical judgment remains of great value in the diagnosis of acute appendicitis.
AB  - BACKGROUND: Observation and repeated examination may lead to favourable clinical
      outcomes in the ever-challenging diagnosis of appendicitis. The goal of this
      study was to evaluate clinical performance in the diagnosis of suspected
      appendicitis in a centre with limited access to medical imaging technologies and
      to identify factors associated with complicated cases. METHODS: A retrospective
      review of the medical records of 211 consecutive surgical cases of suspected
      appendicitis, spanning an 11-year period, was performed. The delays before
      treatment and the subsequent patient outcomes were evaluated. RESULTS: There were
      8.1% of cases with negative findings on appendectomy, 75.8% with uncomplicated
      appendicitis, 12.3% with complicated appendicitis and 3.8% with other surgical
      conditions. The delay before the first medical consultation was significantly
      longer in patients with complicated appendicitis. The various delays after the
      first medical consultation did not differ significantly between the groups.
      CONCLUSIONS: In the context of limited available medical imaging modalities,
      clinical observation was not associated with an increased incidence of
      complicated appendicitis. The presence of complicated appendicitis was associated
      with the delay before the patient's first medical consultation. Clinical judgment
      can be prioritized and can lead to good clinical performance in the management of
      patients with suspected appendicitis, with no significant increase in rates of
      complicated appendicitis and negative findings on appendectomy.

PMID- 16630420
TI  - Determination of patient quality of life following severe acute pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis results in significant morbidity and
      mortality. Clinical experience suggests a significantly reduced quality of life
      for patients, but few studies exist to confirm this experience. We sought to
      objectively demonstrate patient quality of life after severe acute pancreatitis.
      METHODS: Forty-two patients were assessed 24-36 months after an episode of severe
      acute pancreatitis. Patients completed the English Standard Short Form 36 survey
      (SF-36) and a questionnaire about pancreatic function to assess both their health
      related quality of life and symptoms of pancreatic dysfunction. RESULTS: Compared
      with the general Canadian population, survivors of severe acute pancreatitis had
      significantly reduced SF-36 scores. There is also a significant correlation
      between the Ranson score at presentation and the SF-36 Physical Composite Score
      at time of follow-up (rho = -0.47, p = 0.03). Seventy-six percent of patients had
      ongoing symptoms suggestive of pancreatic dysfunction. These included abdominal
      pain, diarrhea, unintentional weight loss, new onset of diabetes mellitus and the
      need for regular pancreatic enzyme supplementation. CONCLUSIONS: Survivors of
      severe acute pancreatitis had a reduced quality of life compared with healthy
      controls. Higher Ranson scores at presentation may predict which patients are
      more likely to have poorer outcomes in the first few years of their recovery.

PMID- 16630421
TI  - Reinforcement of the suture line with an ePTFE graft attached with histoacryl
      glue in duodenal trauma.
AB  - BACKGROUND: Most duodenal injuries are managed with primary repair, but the
      degree of duodenal-wall injury may threaten the integrity of the primary repair.
      Therefore, we evaluated whether the primary repair site could be reinforced with
      histoacryl glue (HAG) or HAG with an expanded polytetrafluoroethylene (ePTFE)
      mesh. METHODS: Grade 3 duodenal injury in the second portion of the rat duodenum
      was chosen as a standard trauma model. Thirty-three male rats were divided into
      sham (n = 3), 2-layer primary repair (n = 10), 1-layer primary repair plus HAG
      application (n = 10) and ePTFE attached with HAG over the 1-layer primary repair
      site (n = 10) groups. Ten-day survival, adhesion grades and histological
      assessment were taken as outcome measures. RESULTS: A significant survival
      advantage was identified in the group that had an ePTFE graft attached with HAG
      over a 1-layer repair when compared with the group that had a 2-layer primary
      repair. Adhesion grades were found to be particularly increased in the group that
      had an ePTFE graft attached with HAG over the primary repair site, moderately
      increased in the primary repair plus HAG application group and lower in the 2
      layer primary repair group. ePTFE graft application was found to be beneficial to
      coverage of the HAG-dependent empty spaces in the serosal layer. CONCLUSIONS: A
      primary repair site after duodenal trauma or a difficult duodenal stump can be
      reinforced with the application of HAG or ePTFE graft implantation with HAG.

PMID- 16630422
TI  - A screening program to identify risk factors for abdominal aortic aneurysms.
AB  - BACKGROUND: We aimed to explore the feasibility of a nurse-supervised aneurysm
      screening program to identify any independent risk factors for abdominal aortic
      aneurysm (AAA) formation in high-risk patients. METHODS: We conducted a
      prospective observational study of 90 male patients in a university- affiliated
      hospital in southern Ontario. The patients were prospectively evaluated and all
      underwent abdominal ultrasonography, with the main outcome measure being
      detection of an AAA. RESULTS: AAAs were identified in 18 patients (20%) and had a
      mean diameter of 3.6 (range 2.8-6.0) cm. A separate analysis was performed to
      identify risk factors for the presence of an aneurysm. The presence of carotid
      artery disease proved to be the only statistically significant independent
      predictor of the presence of AAA (odds ratio 2.23, 95% confidence interval 1.76
      2.56). CONCLUSIONS: This study confirms the feasibility of a nurse-supervised AAA
      screening program, and on the basis of these results we recommend
      ultrasonographic screening for AAA in patients with a history of carotid artery
      disease.

PMID- 16630423
TI  - The new cardiac surgery patient: defying previous expectations.
AB  - BACKGROUND: Studies conducted before 1999 of patients who had coronary artery
      bypass graft surgery (CABG) have shown a tendency toward increasing preoperative
      risk factors. This study examines whether this trend of increasing risk in
      patients who have cardiac surgery has continued since 1999 and whether its effect
      on mortality and morbidity has changed. METHODS: We prospectively collected data
      for 2754 patients who had cardiac surgery, divided them into 4 cohorts based on
      the year of operation (2000-2003) and analyzed the data according to 56
      predefined preoperative, operative and postoperative variables. RESULTS: There
      were no significant changes in most preoperative risk factors over time, except
      for significant decreases in the proportion of elective (p = 0.016) and
      emergency/salvage operations (p < 0.001) and increases in urgent procedures and
      in the number of patients with congestive heart failure (CHF) (p < 0.001). The
      proportion of CABG procedures decreased significantly, whereas the proportion of
      valve, CABG plus valve, and non-CABG surgeries increased. A significant increase
      in multiarterial graft use and a decrease in off-pump coronary artery bypass
      procedures were observed. Postoperative complication rates did not change during
      the 4 years except for a significant decrease in wound infections. No significant
      changes in overall mortality and mortality across types of procedure were
      observed. Median observed/expected ratios for expected length of stay in hospital
      and risk of mortality did not change significantly over time. CONCLUSION:
      Patients' risk factors, except for CHF, did not change from 2000 to 2003. Despite
      more complicated procedures, the postoperative complication rates did not change
      except for a decrease in wound infections. These results suggest that the
      assumption of an inexorably increasing patient risk profile should be re
      evaluated.

PMID- 16630424
TI  - Factors predicting the outcome of primary clubfoot surgery.
AB  - BACKGROUND: We aimed to determine the rate of further surgery, the functional
      outcome and the factors associated with outcome after primary clubfoot surgery.
      METHOD: We conducted a retrospective study of a cohort of all children who were
      less than 2 years of age at the time of surgery for idiopathic clubfoot deformity
      at the Hospital for Sick Children, Toronto, Ont., a tertiary care pediatric
      hospital. Of the 91 families who could be contacted, 63 agreed to return. The
      children's charts were reviewed, and their feet were given a Functional Rating
      System (FRS) score. RESULTS: Of the original operated population (n = 126), 75%
      were male and 41% had bilateral clubfoot. The average age at the time of surgery
      was 8 months, and the mean follow-up was 80.6 months. Further surgery was
      performed in 19% of cases. The mean FRS outcome score was 79. On average, the FRS
      score increased by 1.9 points as age at the time of surgery increased by 1 month.
      Only the presurgical talocalcaneal index was associated with the need for further
      surgery. CONCLUSION: The need for further surgery was 19% overall. Children who
      had surgery closer to 12 months of age had better functional results. Therefore,
      surgery should probably be performed in the second, rather than the first, 6
      months of life.

PMID- 16630425
TI  - Radiology for the surgeon. Soft-tissue case 58: incarcerated Grynfeltt hernia.

PMID- 16630426
TI  - Surgical technique. Technical notes on reduction of thoracic spine fracture
      dislocation.

PMID- 16630427
TI  - [Gallbladder tuberculosis].

PMID- 16630428
TI  - Preoperative fasting guidelines.

PMID- 16630430
TI  - PVT after splenectomy.

PMID- 16630435
TI  - Feasibility of same day discharge after mini-laparotomy cholecystectomy -- a
      simulation study in a rural teaching hospital.
AB  - OBJECTIVE: Open cholecystectomy is still widely practised, more so in the
      developing countries, due to the high cost of laparoscopic cholecystectomy.
      However, the long traditional postoperative stay (7-8 days) prevents rapid
      turnover and adds to the waiting list. The aim of this study was to evaluate
      whether mini-laparotomy cholecystectomy (MLC) can be done as a day surgery or
      extended day surgery in a rural setting. METHODS: A nonrandomized, uncontrolled
      study was done prospectively at the North Bengal Medical College and Hospital.
      The subjects underwent mini-laparotomy cholecystectomy under general or epidural
      anesthesia. Postoperatively they were encouraged to be ambulant early and to
      accept oral fluids. In the evening they were assessed, by preset criteria, for
      fitness for discharge. None were actually discharged but were observed overnight
      and reassessed the next morning, by the same criteria, for any adverse effects
      that could have occurred had they actually been discharged on the same day. They
      were discharged after removal of stitches. Any complications of the surgery were
      also noted. RESULTS: Thirty-two patients (26 females, 6 males) formed the study
      group. General anesthesia was given in 19 cases and epidural in 13. Using the
      scoring system, 25 (78.1%) patients were considered fit for discharge on the
      evening of surgery. The most prominent reasons for non discharge were vomiting
      and pain. Re-evaluation on the following morning showed that 30 (93.75%) patients
      were in a position to be discharged. None showed any complication that would have
      required readmission. There were no significant complications pertaining to the
      procedure itself. CONCLUSION: Mini-laparotomy cholecystectomy as day surgery or
      extended day surgery is feasible and a safe, well tolerated procedure in a wide
      range of age groups. It may be a good alternative to laparoscopic cholecystectomy
      in developing countries, where resources are limited and waiting lists are long.

PMID- 16630436
TI  - Introducing a nurse practitioner: experiences in a rural Alberta family practice
      clinic.
AB  - OBJECTIVE: To report on the experiences of introducing a nurse practitioner (NP)
      into a rural physicians' clinic in Taber, Alberta. DESIGN: Case study, grounded
      theory qualitative approach. SETTING: A rural community-based family practice in
      Taber, Alberta. PARTICIPANTS: Twenty relevant stakeholders, including physicians,
      office staff, Regional Health Authority health professionals and community
      members. METHOD: Open-ended interviews supplemented with a patient survey,
      billing and work time records. MAIN FINDINGS: Successful introduction of the NP
      in the Taber clinic relied on: 1) flexibility in the first stages of developing
      the role; 2) strong connections to key individuals outside the clinic to maintain
      integration with the community; 3) support and guidance provided by a mentor
      group who assisted in developing positive working relationships; and 4) cost
      sharing (matched with benefits) by the clinic and provincial health system for
      sustainability of the position. CONCLUSIONS: The NP role in Taber was viewed
      positively by clinic physicians and other stakeholders because of high patient
      satisfaction with the NP, billing potential that surpassed salary costs, and
      increased integration of physician services with RHA initiatives.

PMID- 16630437
TI  - Health promotion needs of women living in rural areas: an exploratory study.
AB  - OBJECTIVES: To describe the types of health-promoting activities currently
      engaged in by women who live in rural communities, to explore perceived barriers
      and facilitators to staying healthy in rural communities, and to examine how
      these factors may differ for women throughout their adult life. DESIGN:
      Qualitative pilot study. PARTICIPANTS AND SETTING: Women aged 18 years and older
      living in a small rural community in Saskatchewan. METHOD: Eight focus groups
      were conducted with a total of 44 participants who had been stratified into 3 age
      groups. Content analysis of the focus group transcripts was undertaken. MAIN
      FINDINGS: Older women were more likely to report that they engage in a balance of
      activities to promote their physical and mental health. Middle and younger aged
      women, however, were more likely to engage in activities to promote their
      physical health, with less emphasis on their mental health. Among the 3 age
      groups, exercise and nutrition-related activities were most commonly reported.
      Social support and the "rural way of life" were the most commonly reported
      community supports available to these women. Younger women were more likely to
      discuss family commitments as a barrier to maintaining physical fitness,and older
      women discussed the impact that loneliness and lack of appropriate exercise
      options had on healthy living in their community. CONCLUSION: The interviews
      provided a chance for a group of rural women to paint their own picture of
      promoting and maintaining their health in their own community. The activities
      engaged in by women to maintain their health, and the barriers and facilitators
      to staying healthy were different for women of different ages. It is useful for
      health planners to understand how women's health promotion needs vary across
      their adult life span.

PMID- 16630438
TI  - Sealer's finger.

PMID- 16630439
TI  - Country cardiograms case 30. Atrial flutter with aberrancy, and 3:2 A-V
      conduction.

PMID- 16630440
TI  - The occasional extensor tendon laceration repair.

PMID- 16630441
TI  - Generalism versus subspecialization: changes necessary in medical education.
AB  - During the initial Partners Meeting of the Association of Faculties of Medicine
      of Canada (AFMC), the Canadian Association for Medical Education (CAME), the
      College of Family Physicians of Canada (CFPC), the Medical Council of Canada
      (MCC), and the Royal College of Physicians and Surgeons of Canada (RCPSC) in May
      2005, a plenary discussion and debate focused on the tensions that exist between
      generalist and subspecialty education within both the undergraduate and
      postgraduate educational programs in Canadian medical schools. Key issues
      identified in the debate included medical student selection, generalist
      representation on medical school faculty and in learning experiences, and the
      need for a greater teaching role and respect for generalism to be developed.

PMID- 16630442
TI  - It takes more than rural roots to make a rural doc.

PMID- 16630443
TI  - Adverse drug reactions.

PMID- 16630445
TI  - [Gene mutations and dilated cardiomyopathy].

PMID- 16630446
TI  - [New trends of pathogenesis and therapy in dilated cardiomyopathy].

PMID- 16630447
TI  - [Introducing the recent recommendation on diagnosis and treatment of dilated
      cardiomyopathy in USA and European].

PMID- 16630448
TI  - [Stem cells transplantation on dilated cardiomyopathy].

PMID- 16630449
TI  - [Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with
      familial hypertrophic cardiomyopathy and the correlation between genotype and
      phenotype].
AB  - OBJECTIVE: The aim of this study was to screen the disease-causing gene mutations
      and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with
      familial hypertrophic cardiomyopathy (HCM). METHODS: There are 91 family members
      from these 10 pedigrees and 5 members were normal mutated carriers, 23 members
      were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions
      of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and
      cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing
      technique. Clinical information from all patients was also evaluated in regard to
      the genotype. RESULTS: Mutations were found in 5 out of 10 pedigrees. Mutations
      in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3
      patients from these pedigrees suffered sudden death at age 20-48 years old during
      sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation
      (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift
      mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation
      was identified in TNNT2. CONCLUSIONS: Although the Han Chinese is a relatively
      homogeneous ethnic group, different HCM gene mutations were responsible for
      familiar HCM suggesting the heterogeneity nature of the disease-causing genes and
      HCM MYH7 mutations are associated with a higher risk of sudden death in this
      cohort. Furthermore, identical mutation might result in different phenotypes
      suggesting that multiple factors might be involved in the pathogenesis of
      familiar HCM.

PMID- 16630450
TI  - [Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta
      myosin heavy chain gene in a Chinese pedigree].
AB  - OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically
      heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta
      MHC) gene was found in 3 Spanish families with malignant HCM. We detected this
      gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy. METHODS:
      Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were
      chosen for the study. The exons in the functional regions of the beta-MHC gene
      were amplified with PCR and the products were sequenced, genotype and phenotype
      analyzed. RESULTS: Arg723Gly mutation was identified in exon 20 in one pedigree.
      In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of
      heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of
      them had NYHA III and 2 of them were diagnosed as HCM before the age of 20.
      CONCLUSIONS: Arg723Gly mutation was also one of the main disease-causing genes in
      Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown
      by early progressive heart failure development and poor prognosis in this
      pedigree with Arg723Gly mutation.

PMID- 16630451
TI  - [Effect of valsartan on Tribble 3 gene expression in rats with experimental
      diabetic cardiomyopathy].
AB  - OBJECTIVE: Tribbles, a protein family controlling mitogen-activated protein
      kinase cascades, might contribute to the remodeling process in dilated
      cardiomyopathy. We investigated the gene expression of Tribble 3 (TRB(3)),
      cardiac function and collagen changes in rats with diabetic cardiomyopathy (DCM)
      and the modulating effects of valsartan on them. METHODS: Male Wistar rats were
      fed with high cholesterol diet throughout the study period, streptozocin (30
      mg/kg, i.p) was given at the 28th day, valsartan (30 mg.kg(-1).d(-1), n = 13) or
      placebo (n = 11) was administered at the 35th day to rats with fasting blood
      glucose > or = 11.1 mmol/L per gavage for another 12 weeks. Control rats (n = 8)
      were fed with regular chow. Fasting blood glucose was monitored throughout the
      study, left ventricular function was determined by echocardiography, myocardial
      collagen content quantified after Masson-staining and myocardial mRNA expression
      of TRB(3) detected by quantification real-time RT-PCR at the end of study.
      RESULTS: Cardiac function was significantly improved (EF: 74% +/- 10% vs. 66% +/-
      7%, P < 0.05), myocardial collagen content decreased (13.23 +/- 3.14 vs. 16.92 +/
      3.18, P < 0.05) in rats with DCM treated with valsartan. Moreover, TRB(3) mRNA
      was significantly increased in rats with DCM compared to control rats (0.0198 +/-
      0.0082 vs. 0.1108 +/- 0.0933, P < 0.05) and the increase could be significantly
      attenuated by valsartan (0.0367 +/- 0.0234, P < 0.05 vs. DCM). A significant
      positive correlation was observed between myocardial TRB(3) mRNA and myocardial
      collagen content (r = 0.67, P < 0.05) and between TRB(3) mRNA and fasting blood
      glucose (r = 0.69, P < 0.05) in rats with DCM. CONCLUSION: Our results show for
      the first time that myocardial TRB(3) mRNA is upregulated in rats with DCM and
      which could be down-regulated by valsartan.

PMID- 16630453
TI  - [The role of glucose/TSP-1/TGFbeta1 signal pathways in diabetic cardiomyopathy].
AB  - OBJECTIVE: Hyperglycemia could upregulate transforming growth factor-beta
      (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the
      rat in vivo and myocardial fibrosis was related to cardiac dysfunction in
      diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal
      pathways in the development of diabetic cardiomyopathy (DCM). METHODS: Male
      Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30
      mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or =
      11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11).
      Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was
      monitored throughout the study. After hemodynamic measurements by the end of the
      study, myocardial collagen content was quantified in Masson-stained samples and
      the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real
      time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were
      detected by Western blot. RESULTS: Compared with control group, cardiac function
      was decreased as shown by significantly reduced left ventricular systolic
      pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was
      significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P <
      0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein
      expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also
      significantly higher than those of the control group. Moreover, myocardial
      collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions
      of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were
      positively correlated to FBG and myocardial collagen (P < 0.05). However, there
      were no correlations between the protein expression of latent TGFbeta(1) and FBG
      and myocardial collagen. CONCLUSION: The pathway of glucose/TSP-1/TGFbeta(1)
      might play an important role in myocardial interstitial fibrosis of DCM. It may
      be the basis of novel therapeutic approaches for ameliorating DCM.

PMID- 16630454
TI  - [Comparison of the effects of intravenous recombinant human brain natriuretic
      peptide and nitroglycerin in patients with decompensated acute heart failure: a
      multicenter, randomized, open-label, parallel-design study].
AB  - OBJECTIVE: To compare the efficacy and safety of intravenous infusion recombinant
      human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in treating
      patients with decompensated acute heart failure. METHODS: A total of 209 patients
      characterized of decompensated acute heart failure were enrolled in this
      multicenter, randomized, open-label, parallel-design study. The patients were
      randomly allocated to catheter group and non-catheter group (depending on the use
      of Swan-Ganz). Each group was then randomly assigned to receive rhBNP (0.15
      microg/kg bolus intravenous injection followed by 0.0075 microg.kg(-1).min(-1)
      for 24 hours, n = 105) or NIT (starting at 10 microg/min and increasing 5
      microg/min each time till clinical effective dose for 24 hours, n = 104). Blood
      pressure, heart rate, dyspnea grade, 24 hours fluid in- and output and
      improvement in patient symptoms and signs were evaluated and adverse events were
      documented. RESULTS: Urine output was significantly increased after both rhBNP
      and NIT treatments. Dyspnea and symptom improvements were more significant in
      rhBNP group compared to NIT group. PCWP and PAP were both decreased after rhBNP
      and NIT therapies and there was more significant reduction in PCWP and PAP
      between 30 min and 2 hours in rhBNP group compared to NIT group. However, RAP and
      CI were similar between the two groups at various time points. The total adverse
      events were comparable between the two groups (20.0% vs. 19.2%, P > 0.05) and 7
      patients withdrew the study due to adverse events (4 in rhBNP and 3 in NIT
      group). CONCLUSIONS: rhBNP is superior to nitroglycerin in improving dyspnea and
      symptoms and decreasing PCWP and PAP in patients with decompensated acute heart
      failure patients. The safety of rhBNP was comparable to nitroglycerin in treating
      patients with decompensated acute heart failure.

PMID- 16630456
TI  - [Clinical features of patients with atypical coronary artery spasm].
AB  - OBJECTIVE: This study is aimed to compare the clinical characteristics of
      patients with typical and atypical coronary artery spasm. METHODS: Out of 64
      patients with chest pain at rest and without significant coronary artery
      stenosis, coronary artery spasm was provoked by intracoronary injection of
      acetylcholine in 46 patients, including 12 with ST segment elevation (typical
      coronary artery spasm group) and 34 without ST segment elevation (atypical
      coronary artery spasm group). The demographic data, coronary angiographic
      findings, treadmill electrocardiogram, dipyridamole and rest thallium-201
      myocardial perfusion computed tomography, and the follow-up clinical data of the
      two groups were compared. RESULTS: The patients with typical coronary artery
      spasm were younger (47 +/- 6 vs. 58 +/- 12, P < 0.05) than patients with atypical
      coronary artery spasm group. Hyperlipidemia were more common in atypical coronary
      artery spasm group (74% vs. 33%, P < 0.05) and myocardial bridging was more
      common in patients with typical coronary artery spasm group (67% vs. 32%, P <
      0.01). Focal coronary spasm during acetylcholine provocation was seen in 92%
      patients with typical coronary spasm and in 32% patients with a atypical coronary
      artery spasm (P < 0.01) while diffuse coronary spasm was seen in 8% patients with
      typical coronary spasm and in 68% patients with a atypical coronary artery spasm
      (P < 0.01). All patients with coronary artery spasm were treated with aspirin,
      calcium channel blockers, long-acting nitroglycerine, with or without lipid
      lowering drugs, 2 patients with typical coronary spasm and 4 patients with
      atypical coronary spasm were rehospitalized due to chest pain and rest of the
      patients remained free of chest pain during the median follow-up period of 18 +/-
      14 months. CONCLUSION: Atypical coronary artery spasm is common in patients with
      rest angina and diffuse coronary microvascular spasm might be the cause of chest
      pain in these patients.

PMID- 16630457
TI  - [Pathologic changes of the cardiac conduction system in 12 patients with abnormal
      ECG].
AB  - OBJECTIVE: To investigate the relationship between abnormal ECG and pathologic
      changes in the cardiac conduction system (CCS). METHOD: Pathological changes of
      the CCS in 12 cases with abnormal ECG out of 16 pre-death ECG were observed.
      RESULTS: (1) Among 7 cases of sudden cardiac death, ECG monitoring recorded
      bradyarrhythmia in 6 cases, tachyarrhythmia 6 cases, bradycardia-tachycardia
      syndrome 2 cases, conduction block 6 cases, atrial premature beats 6 cases,
      ventricular premature beats 6 cases, and ST-T changes 4 cases. (2) The
      histopathological findings in the CCS were noted in all cases. Of these 12 cases,
      three had signs of fatty infiltration, and/or fibrous 4 cases, three of
      amyloidosis, one of chronic inflammatory changes, two of acute inflammatory
      changes, two of developmental anomalies, two of hemorrhages and one of LAD
      stenosis. (3) Acute inflammation changes in the CCS corresponded to
      tachyarrhythmia and multiple ventricular premature beats, whereas chronic
      inflammation and degenerative changes in the CCS were often related to
      bradyarrhythmia, bradycardia-tachycardia syndrome and conduction block. (4) The
      CCS changes alone could lead to ST-T changes in ECG. CONCLUSION: The pathological
      changes in the CCS are related to ECG changes, and attributed to the pathological
      bases of arrhythmia.

PMID- 16630458
TI  - [Effects of intraoperative hybrid procedures for the treatment of congenital
      heart disease].
AB  - OBJECTIVE: A hybrid operation is a joint procedure involving the interventional
      cardiologist and the cardiac surgeon concomitantly to optimize surgical
      management for complex congenital heart disease. We analyzed the feasibility and
      efficacy of this procedure in 20 patients with congenital heart disease. METHODS:
      Data from 20 patients who underwent intraoperative hybrid procedures from March
      to October 2005 were analyzed. Two groups were identified: (1) Balloon
      valvuloplasty group: pulmonary atresia with intact ventricular septum in neonate
      (n = 3) and severe pulmonary stenosis in infants (n = 4); (2) Device closure
      group: atrial septum defects (ASD) in child (n = 7), adult ASD (n = 3) and
      multiple ventricular septum defect (VSD, n = 3). Pulmonary balloon dilation under
      the guidance of echocardiography together with modified Blalock-Taussig shunt
      procedure and PDA ligation were applied to patients in balloon valvuloplasty
      group. For ASD patients, the occluder was placed via right atria after opening
      the chest either with median sternotomy (4 case) or with submaxillary minimally
      invasive incision (6 cases), PDA ligation was performed in 1 patient and 2
      coronary artery bypass surgeries were performed in 2 adult ASD patients
      complicating CHD. For multiple VSD, perimembranous VSD was closed surgically and
      muscular VSD closed by occluder via tricuspid valve approach under
      cardiopulmonary bypass. RESULTS: All operations were successful and 1 infant
      received another conventional valvuloplasty due to the pulmonary restenosis after
      initial balloon valvuloplasty and 1 patient's muscular VSD was closed by
      conventional procedure after unsuccessful device closure. No device-related
      complications were found during follow-up (1-6 months). CONCLUSION: Our results
      showed that intraoperative hybrid procedure was feasible and effective in
      selected patients with congenital heart disease.

PMID- 16630459
TI  - [Transcatheter closure of ruptured sinus of valsalva aneurysm using Amplatzer
      duct occluder].
AB  - OBJECTIVE: The present study was conducted to investigate the feasibility and
      efficacy of transcatheter closure of ruptured sinus of Valsalva aneurysm (RSVA).
      METHODS: Four patients (3 females) aged 7-57 years with RSVA (3 congenital RSVA
      and 1 post-surgery RSVA) were involved in the present study. Two-dimensional and
      color Doppler echocardiography revealed the ruptures of right coronary sinus into
      right ventricle in all cases. The echo estimated size of the defect was 2-10 mm.
      After the establishment of the arterio-venous wire loop, Amplatzer Duct Occluder
      (ADO) was successfully deployed by antegrade venous approach in all patients. The
      diameter of the occluder was chosen to be at least 1 to 2 mm larger than defect.
      RESULTS: The defects were successfully occluded without any complications. On the
      follow-up 3 months after operation, there was no device embolization, infective
      endocarditis and aortic regurgitation. CONCLUSION: Transcatheter closure is a
      feasible and effective modality for RSVA without other anomalies.

PMID- 16630460
TI  - [The prognostic value of hyponatremia in patients with acute myocardial
      infarction].
AB  - OBJECTIVE: To evaluate the prognostic significance of hyponatremia in patients
      with AMI. METHODS: The study population consisted of 670 patients with AMI in
      coronary care unit in our hospital from January 2003 to December 2004. The
      patients were designed into three groups according to serum sodium concentration
      within twenty four to forty eight hours following the onset of AMI: Group A.
      Na(+) > or = 135 mmol/L; Group B. Na(+) 120-135 mmol/L; Group C. Na(+) < or = 120
      mmol/L. The data of myocardial enzymes, myocardial infarction size, heart
      function and inhospital mortality were analyzed retrospectively. RESULTS: 1. The
      inhospital mortality of each group: group A was 7.6% (17/225), group B was 8.1%
      (34/421), group C was 33.3% (8/24). The difference between group C and group B or
      group A was significant. The P value was little than 0.05. 2. Activities of serum
      creatine phosphatase kinase and serum creatine phosphatase kinase isoenzymes and
      myocardial infarction sizes in each group were different (P < 0.05). 3. 59 cases
      of all died and 611 cases of all recovered in duration of hospital stay. Serum
      sodium concentrations of the recovered group were (133.00 +/- 5.25) mmol/L, and
      that of the died group were (122.00 +/- 7.25) mmol/L (P < 0.01). 4. In a
      multivariate logistic regression analysis, hyponatremia was associated with 30
      day mortality in patients with AMI. In analysis of the association between the
      degree of hyponatremia and outcome, we observed that the risk of 30-day mortality
      increased with the severity of hyponatremia. CONCLUSION: Hyponatremia may be one
      of the important markers that predict a worse prognosis in patients with AMI.

PMID- 16630464
TI  - [Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb
      ischemia].
AB  - OBJECTIVE: We investigated the effects of pitavastatin on angiogenesis and
      perfusion in C3H/He mice with unilateral hind limb ischemia. METHODS: C3H/He mice
      treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per
      gavage for 1 week underwent unilateral hind limb ischemia surgery and were
      treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler
      perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately
      after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel
      counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme
      histochemical technique, vascular endothelial growth factors (VEGFs) expression
      in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by
      chrome dioxide Griess method. RESULTS: Lower extremity perfusion was
      significantly improved in pitavastatin treated mice vs. controls as measured by
      LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment
      was associated with significantly increased capillary count [(47 +/- 11) vs. (26
      +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho
      Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P <
      0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P
      < 0.05) and VEGF protein expression in ischemic limbs were also significantly
      increased in pitavastatin group than those in control group. CONCLUSIONS:
      Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb
      ischemia.

PMID- 16630465
TI  - [Effects of granulocyte colony-stimulating factor on peripheral endothelial
      progenitor cells in cholesterol-fed rabbits].
AB  - OBJECTIVE: To investigate the effects of granulocyte colony-stimulating factor (G
      CSF) on peripheral endothelial progenitor cells (EPC) and atherosclerosis (AS) in
      cholesterol-fed rabbits. METHODS: Male New Zealand white rabbits were randomly
      divided into control group, G group (Recombinant Human Granulocyte Colony
      Stimulating Factor Injection rhG-CSF 50 microg/d), AS group (high cholesterol
      diet) and G + AS group (rhG-CSF 50 microg/d plus high cholesterol diet, n = 8 per
      group). Peripheral blood was collected at baseline and at 1, 4, 8 and 12 weeks,
      total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll
      density gradient centrifugation, and then the cells were plated on fibronectin
      coated culture dishes. After being cultured for 7 days, EPCs were characterized
      as adherent cells double positive for DiLDL uptake and lectin binding by direct
      fluorescent staining under a laser scanning confocal microscope. After being
      cultured for 3 days, the number of EPC (PE-CD34/FITC-CD133 double-stained
      positive cells) was quantified by flow cytometric analysis. Serum NO was measured
      and aortic plaque area analyzed at 12 weeks. RESULTS: EPC number was low in
      control and AS groups and EPC number was significantly increased ( approximately
      13-fold, P < 0.001) compared to baseline at 1 week in G and G + AS groups and
      remained at this level throughout the study period in G group while decreased
      gradually in G + AS group and returned to baseline level at 12 weeks. Aortic
      atherosclerotic plaque was visible in both AS and G + AS groups, however, the
      aortic atherosclerotic plaque area was smaller in G + AS group than that of in As
      group (59.8 mm(2) +/- 26.9 mm(2) vs. 251.5 mm(2) +/- 83.4 mm(2), P < 0.01). Serum
      NO was similar between AS and G + AS groups and significantly higher than that in
      control and G groups. CONCLUSION: CSF could attenuate atherosclerosis in
      cholesterol-fed rabbits by increasing circulating EPC.

PMID- 16630467
TI  - [Tyrosine kinase dependent lectin-like oxidized LDL receptor-1 upregulation by
      thrombin and factor Xa in vascular smooth muscle cells].
AB  - OBJECTIVE: Thrombin and factor Xa are key players in the process of arterial
      thrombi formation and lectin-like oxidized low density lipoprotein receptor-1
      (LOX-1) is a cell surface endocytosis receptor for atherogenic oxidized LDL (ox
      LDL). Here we investigate whether thrombin and factor Xa can induce LOX-1 protein
      expressions in cell-associated forms and soluble forms in cultured bovine aortic
      smooth muscle cells (BSMCs). METHODS: BSMCs were treated with thrombin or factor
      Xa in the presence or absence of AG1478, an epidermal growth factor (EGF)
      receptor-associated tyrosine kinase inhibitor. Total cell lysates and
      concentrated culture medium were then analyzed by Western blot using a mouse anti
      LOX-1 monoclonal antibody. RESULTS: LOX-1 protein levels in cell lysates and
      culture medium were significantly increased by thrombin and factor Xa in a
      concentration- and time-dependent manner. Upregulation of LOX-1 protein
      expressions in cell lysates and concentrated culture medium was observed at
      concentrations above 2.0 and 3.0 U/ml of thrombin and 50 and 100 nmol/L of factor
      Xa, respectively. Increased LOX-1 protein expressions in cell lysates and cell
      culture medium were detectable as early as 4 h and peaked at 12 h after treatment
      with thrombin or factor Xa. LOX-1 expression induced by thrombin and factor Xa
      could be blocked by pretreatment with AG1478. CONCLUSIONS: Thrombin and factor Xa
      can act as LOX-1 inducers via tyrosine kinase activation.

PMID- 16630471
TI  - [The impact of two continuing education models on competence for hypertension
      diagnosis and treatment of community physicians].
AB  - OBJECTIVE: To compare the impact of two different continuing education models:
      traditional model and a new model entitled "problem-oriented and case-based"
      mutual pattern and "train the trainer" course, on improving hypertension
      diagnosis and treatment competence of community physicians. METHODS: A total of
      632 physicians from 22 district and community hospitals in Haidian district (new
      model) and 20 district and community hospitals in Chaoyang district (traditional
      model) in Beijing were trained during July to October 2002. The survey was
      carried out before and 2 years after training with examination questionnaire.
      RESULTS: The competence evaluated as a score (maximal 100) for hypertension
      diagnosis and treatment of physicians was similar in physicians before training
      from the two districts. Post training, the score significantly increased from
      40.0 to 47.4 (P < 0.01) in physicians from Chaoyang district and from 40.5 to
      70.5 (P < 0.01) in physicians from Haidian district and the final score for
      physicians from Haidian district is significantly higher than that for physicians
      from increased from Chaoyang district (P < 0.01). CONCLUSION: The new model is
      more efficient for improving community physician's competence for diagnosing and
      treating hypertension.

PMID- 16630473
TI  - [Pulmonary embolism misdiagnosis in China: a literature review (2001 to 2004)].
AB  - OBJECTIVE: To evaluate the present status of pulmonary embolism (PE) misdiagnosis
      in China. METHODS: Documents on PE misdiagnosis published in Chinese-language
      journals between 2001 and 2004 were identified by searching the China Hospital
      Knowledge Database in China National Knowledge Infrastructure Web (CNKI-CHKD).
      Retrospective review items include: patient symptoms, medical examination tools,
      treatments and prognosis, causes of death, hospitals involved. The recent
      situation on PE misdiagnosis was also compared to that in year between 1980 to
      2000. The number of published literatures on PE and PE misdiagnosis from 1994 to
      2004 was also searched. RESULTS: (1) A total of 110 documents with 1540
      misdiagnosed PE patients were found. The misdiagnosis time varies from 0.5 hour
      to 16 years and was 1.86 years on average. (2) Once the misdiagnosis be
      corrected, the prognosis could be improved by antithrombotic and thrombolytic
      therapies compared with those without antithrombotic and thrombolytic therapies
      (OR 11.67, 95% CI 5.861-23.249). The major causes of death were sudden death,
      resistant shock in patients without antithrombotic and thrombolytic therapies
      while the causes were sudden death, cerebral hemorrhage and resistant shock in PE
      patients received antithrombotic and thrombolytic therapies. (3) Literatures on
      PE misdiagnosis were most from provincial hospitals [37 papers with 547 cases
      (33.6%, 35.5%)] and municipal hospitals [43 papers with 671 cases (39.1%,
      43.6%)]. (4) The number of papers published on PE and PE misdiagnosis from 1994
      to 2004 increased steadily by an average of 26.6% and 9.1%, respectively. (5) PE
      was misdiagnosed to more than 70 kinds of diseases and the top 4 were coronary
      heart disease in 449 cases (26.8%), pneumonia in 217 cases (12.9%), congestive
      heart failure in 142 cases (8.5%) and pleurisy in 114 cases (6.8%). CONCLUSIONS:
      (1) PE misdiagnosis is still a critical issue now in China and early diagnosis
      and effective treatment is essential for a better prognosis. (2) The differential
      diagnosis among PE and coronary heart disease and pneumonia need to be emphasized
      to avoid the PE misdiagnosis. (3) Efforts should be made through continuing
      education on clinical professionals to improve their knowledge on PE in China.

PMID- 16630474
TI  - [The clinical use of aspirin in patients with atherosclerotic cardiovascular
      disease: 2005 Chinese Expert Consensus Document].

PMID- 16630475
TI  - [Research progress of atherosclerotic plaque erosion and thrombogenesis].

PMID- 16630477
TI  - [Serrated lesions and carcinoma of colorectum].

PMID- 16630478
TI  - [Two novel germline mutations of MLH1 in hereditary nonpolyposis colorectal
      cancer family].
AB  - OBJECTIVE: To explore germline mutations of MLH1 in hereditary nonpolyposis
      colorectal cancer (HNPCC), and to investigate the pathobiology of novel
      detectable mutations of MLH1. METHOD: RNA was extracted from the peripheral blood
      of 12 patients from 12 different families fulfilling the Amsterdam II Criteria of
      HNPCC. Germline mutations of MLH1 were determined by RT-PCR with gene specific
      primers, heat-resistance reverse transcriptase and long-template PCR polymerase,
      followed by cDNA sequencing analysis. PCR-Genescan analysis was used to further
      investigate microsatellite instability with a panel of 5 microsatellite markers
      (BAT26, BAT25, D5S346, D2S123 and Mfd15), along with immunohistochemistry
      staining to detect the expression of MLH1 protein in the tumor tissues. RESULTS:
      Four germline mutations were found in 4 patients, 2 of which were previously
      reported GTT-->GAT mutation at codon 384 of exon 12, and the other two were novel
      mutations: CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon
      16. Two tumors with the novel mutations had high frequency microsatellite
      instability showing more than 2 instable loci (RER + phenotype), and both tumors
      lost their MLH1 protein expression. CONCLUSION: The two novel germline mutations
      of MLH1 identified in this study, i.e. CGC-->TGC at codon 217 of exon 8 and CCG-
      >CTG at codon 581 of exon 16, are very likely to have pathological significance.

PMID- 16630479
TI  - [Ultrastructural features and platelet-derived growth factor receptor A gene
      mutations in CD117-negative gastrointestinal stromal tumor].
AB  - OBJECTIVE: To explore the ultrastructural features and mutation status of
      platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal
      stromal tumors that were immunohistochemically negative for CD117 antigen.
      METHODS: Six cases of gastrointestinal stromal tumors that were CD117 immunostain
      negative were studied by electron microscopy. Direct PCR sequencing was used to
      investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene
      exons 12 and 18. RESULTS: The ultrastructural features of all 6 cases were
      similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases
      were found to have c-kit gene mutations. However, three tumors were found to
      harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-
      >Val842 missense mutation and one having an Arg-->Ser841 missense mutation.
      CONCLUSIONS: PDGFRA mutations may provide an important alternative molecular
      mechanism for the development of gastrointestinal stromal tumor.

PMID- 16630480
TI  - [Diagnosis and differential diagnosis of intraductal papillary mucinous neoplasm
      of pancreas].
AB  - OBJECTIVE: To study the clinicopathologic features of intraductal papillary
      mucinous neoplasm (IPMN) and its distinction from mucinous cystic neoplasm of
      pancreas. METHODS: The clinical, radiologic and histologic features of 17 cases
      of IPMN and 13 cases of mucinous cystic neoplasm (MCN) were reviewed. Mucin
      profiles (MUC1, MUC2 and MUC5AC) were studied by histology (HE) and
      immunohistochemistry (EnVision). RESULTS: 10 of the 17 cases of IPMN were males.
      13 cases of the IPMN were located in head of pancreas. Communication with the
      main pancreatic duct was demonstrated in 15 cases. Histologically, there were
      mild to severe papillary ingrowths of dysplastic epithelial cells, associated
      with intervening normal or atrophic pancreatic parenchyma. Ovarian-like stroma
      was not seen. Ancillary investigations showed that MUC2 and MUC5AC were detected
      in tumor cells of 9 and 4 cases respectively. The 4 cases with invasive component
      showed MUC1 positivity. On the other hand, 11 of the 13 cases of MCN occurred in
      middle-aged to elderly females and were located in the body and tail of pancreas.
      Ovarian-like stroma was commonly seen and there was no connection with the main
      pancreatic duct. All non-invasive MCN, regardless of the degree of cytologic
      atypia, were positive for MUC5AC (but not MUC2). In the 2 cases with invasive
      component, MUC1 expression was observed, as in IPMN. CONCLUSIONS: The age and sex
      of patients, tumor location, absence of ovarian-like stroma, communication with
      main pancreatic duct and characteristic mucin profiles represent useful
      parameters in distinguishing IPMN from MCN of pancreas. The tumor cells of IPMN
      express mainly MUC2, while those of MCN express MUC5AC. MUC1 may also be a useful
      marker in demonstration of stromal invasion in these tumors.

PMID- 16630481
TI  - [Study of expression of CD138 and heparinase in hepatocellular carcinoma by
      tissue microarray].
AB  - OBJECTIVE: To study the expression of CD138 and heparinase in hepatocellular
      carcinoma (HCC) and its relationship with tumor development, progression,
      metastasis and recurrence. METHODS: Tissue microarray and immunohistochemical
      study (EnVision method) for CD138 and heparinase was performed on tissue
      microarray which consisted of 197 cases of HCC, including adjacent non-neoplastic
      liver tissues, and 66 cases of HCC metastases. RESULTS: The rates of CD138
      expression in HCC and adjacent non-neoplastic liver tissues were 48.7% (96/197)
      and 65.0% (128/197, P < 0.05) respectively. In early-stage and late-stage tumors,
      the expression rates were 61.7% (29/47) and 44.7% (67/150, P < 0.05)
      respectively. The rate in patients with metastasis was 33.3% (22/66), as compared
      with 53.6% (45/84, P < 0.05) in patients without metastasis. In patients with
      tumor recurrence occurring within or after 1 post-operative year, the expression
      rates were 23.3% (7/30) and 61.1% (11/18, P < 0.05) respectively. On the other
      hand, the rates of expression of heparinase in HCC and adjacent non-neoplastic
      liver tissues were 35.5% (70/197) and 12.7% (25/197, P < 0.05) respectively. In
      early-stage and late-stage tumors, the expression rates were 29.8% (14/47) and
      37.3% (56/150, P > 0.05) respectively. The rate in patients with metastasis was
      48.5% (32/66), as compared with 28.6% (24/84, P < 0.05) in patients without
      metastasis. In patients with tumor recurrence occurring within or after 1 post
      operative year, the expression rates were 50.0% (15/30) and 44.4% (8/18, P >
      0.05) respectively. In the 66 cases of metastatic HCC studied, the expression
      rate of CD138 was lower in the heparinase-positive subgroup (P < 0.05).
      CONCLUSIONS: Loss of CD138 expression is related to HCC development, progression,
      metastasis and recurrence. Overexpression of heparinase, when coupled with loss
      of CD138 expression, may take part in tumor metastasis of HCC.

PMID- 16630482
TI  - [Expressions of wildtype-RET and RET/PTC rearrangements in sporadic adult
      papillary thyroid carcinoma and their clinicopathologic correlation].
AB  - OBJECTIVE: To evaluate the expressions of wildtype-RET (WT-RET) and RET/PTC in
      sporadic adult papillary thyroid carcinoma and to investigate their
      clinicopathologic correlation. METHODS: Sixty-six papillary thyroid carcinomas
      (PTC) and thirty-six control cases with frozen and paraffin-embedded tissues were
      analyzed for the expressions of WT-RET and oncogene RET/PTC1 or RET/PTC3 by
      nested RT-PCR. RESULTS: (1) 62 percent (41/66) of PTC patients were above 40
      years of age. Thirty-eight percent (25/66) of the tumors showed lymphocytic
      thyroiditis. Lymph node and distant metastasis were seen in 59% (39/66) and 7.6%
      (5/66) respectively. (2) Forty-five cases (68.1%) of PTCs expressed RET tyrosine
      kinase domain (RET-TK). Simultaneous expressions of RET-BP and TK were seen in
      nineteen PTCs (28.8 %). One of eight adenomas (12.5 %) expressed wild-type RET
      (WT-RET). (3) Fourteen PTCs (21.2%) expressed RET/PTC, including five cases
      expressing RET/PTC1 and nine cases expressing RET/PTC3. Six cases (9%) expressed
      both RET/PTC and WT-RET. (4) Statistic analysis did not show any correlation
      between the expression of WT-RET or RET/PTC and clinicopathologic parameters.
      CONCLUSIONS: The expression of RET/PTC was specific to PTC. However, its
      prevalence was low and, therefore, of limited diagnostic utility. The expression
      patterns of WT-RET in PTC and adenoma suggest that there are different molecular
      mechanisms in activating RET proto-oncogene in thyroid tumors.

PMID- 16630483
TI  - [Detection of API2-MALT1 fusion gene in extranodal B-cell lymphoma and its
      significance].
AB  - OBJECTIVE: To study the expression of API2-MALT1 mRNA in mucosa-associated
      lymphoid tissue (MALT) lymphoma, extranodal diffuse large B-cell lymphoma (DLBCL)
      and Hashimoto's thyroiditis, to investigate the expression pattern of API2-MALT1
      variants, and to correlate the findings with the clinicopathologic features and
      prognosis. METHODS: Sixty-two cases of MALT lymphoma (10 from lung, 31 from
      stomach, 9 from intestine and 12 from thyroid), 32 cases of extranodal DLBCL (16
      from stomach, 13 from intestine and 3 from thyroid), 8 cases of Hashimoto's
      thyroiditis and 5 cases of reactive lymph nodes hyperplasia as negative controls
      were collected. The expression of API2-MALT1 mRNA was studied in all cases by
      reverse transcriptase (RT)-polymerase chain reaction (PCR) and nested PCR. The 94
      cases of lymphoma were subdivided into API2-MALT1-positive and API2-MALT1
      negative groups. Among the patients, 78 were followed up for 6 to 120 months. The
      differences in clinicopathologic features and prognosis between the two groups
      were analyzed. RESULTS: API2-MALT1 transcripts were detected in 39 of the 94
      lymphoma cases (with 28 cases being MALT lymphoma and 11 cases being extranodal
      DLBCL). mRNA expression was not detected in all cases of Hashimoto's thyroiditis
      and the negative controls. Two fusion gene variants, A1446-M1123 and A1446-M814
      were found, and A1446-M1123 expression was more common. As for MALT lymphoma
      cases, the frequency of the fusion gene expression was lower in thyroid, when
      compared with that in lung, stomach and intestine. API2-MALT1-positive cases had
      tumors in an earlier stage with milder infiltration of cancer cells, lower
      relapse rate, and higher five-year survival rate. CONCLUSIONS: The expression of
      API2-MALT1 mRNA can be detected in both MALT lymphoma and extranodal DLBCL, but
      not in Hashimoto's thyroiditis. These cases tend to show a more indolent clinical
      course and better survival. The frequency of t (11; 18) (q21; q21) correlates
      with the primary sites of MALT lymphoma. The higher incidence of breakpoint at
      1123 bp of MALT1 gene in Chinese people may be due to geographical variation.

PMID- 16630484
TI  - [Metanephric stromal tumor: a pathologic study of two cases].
AB  - OBJECTIVE: To study the clinicopathologic features of metanephric stromal tumor
      (MST), with emphasis on diagnostic criteria. METHODS: The clinicopathologic
      findings in 2 cases of MST were analyzed and the literature of this entity was
      reviewed. RESULTS: Cases of MST were unilateral and mostly centered in renal
      medulla. The tumor was separated from adjacent renal tissue by sharp and
      scalloped borders. Entrapped tubules and glomeruli were commonly seen within the
      lesion. The tumor cells were spindle to stellate in shape and arranged in a
      nodular pattern. On low power examination, alternating areas of high and low
      tumor cellularity were noted. Characteristically, there were onion skin-like
      concentric cuffs of tumor cells around entrapped tubules. The small intratumoral
      vasculatures showed irregular thickening ("angiodysplasia"). Immunohistochemical
      study demonstrated that the tumor cells diffusely expressed CD34. CONCLUSIONS:
      Which the tumor cells around the entrapped renal tubules and blood vessels
      imparts a nodular appearance, as well as the tumor cells labbed for CD34 are the
      highly characteristic pathologic findings of MST.

PMID- 16630485
TI  - [Retrovirus-mediated RNA inhibition of EphA2 gene expression in colon
      adenocarcinoma HCT-8 cells].
AB  - OBJECTIVE: To explore novel cancer gene therapy by retrovirus-mediated RNAi
      technique to suppress the endogenous EphA2 oncogene expression in colon
      adenocarcinoma HCT-8 cells. METHODS: Sequence information of EphA2 mRNA was
      selected and two complementary oligonucleotides with hairpin loop were designed.
      Retrovirus-mediated RNAi expression vector (pSIREN-EphA2) was then constructed
      and transfected into the HCT-8 cells. Inhibition of EphA2 protein expression was
      quantitatively determined by Western blot and immunohistochemistry assay (SP
      method). RESULTS: The construction of pSIREN-EphA2 vector was successful and
      confirmed by restriction enzyme analysis and DNA sequencing. The post
      transfection level of EphA2 protein expressions was greatly reduced in HCT-8
      cells transfected with pSIREN-EphA2, as compared with those of untransfected
      cells and the vector control (P < 0.001). CONCLUSIONS: EphA2 protein expression
      in HCT-8 cell line can be suppressed using recombinant retrovirus-mediated RNAi
      technique. This approach may provide a novel gene therapy against colonic
      adenocarcinoma.

PMID- 16630486
TI  - [Mitotic arrest of gastric cancer cells induced by silencing of STK15 gene].
AB  - OBJECTIVE: To investigate the role of STK15 in regulating mitosis of gastric
      cancer cells (MKN45) by gene silencing through RNA interference mechanism.
      METHODS: RNA interference technique was used to inhibit STK15 expression in MKN45
      cells. The expression levels of STK15 mRNA and protein were measured by real-time
      quantitative RT-PCR and Western blot respectively and cell morphological changes
      were investigated by reverse microscopy. In addition, cell cycle distribution and
      cellular proliferation were determined by flow-cytometry and MTT assay
      respectively. Finally, the mitotic phenotype of MKN45 cells was studied by
      immunofluorescence staining and confocal microscopy. RESULTS: Silencing of STK15
      gene by RNA interference was confirmed by marked decrease of STK15 mRNA and
      protein levels in the treated MKN45 cells. This silencing correlated with
      rounding of the cells, decreasing of DNA content in G(2) phase (P < 0.05) and a
      lowered proliferation index (P < 0.05), along with alterations of mitotic
      phenotype of MKN45 (P < 0.05). CONCLUSION: STK15 gene may play a key role in
      regulating cellular mitosis and its inhibition by RNA interference leading to
      mitosis arrest in MKN45 cells.

PMID- 16630487
TI  - [Roles of metabolic syndrome and insulin resistance in carcinogenesis of colon].

PMID- 16630488
TI  - [Mucin gene family and its role in diagnosis of pancreas neoplasms].

PMID- 16630489
TI  - [Pathologic diagnosis and differential diagnosis of precancerous liver lesions
      and well-differentiated hepatocellular carcinoma].

PMID- 16630490
TI  - [Preparation of paraffin sections using snap-frozen renal biopsy tissues].

PMID- 16630491
TI  - [Solid variant of papillar renal cell carcinoma: report of a case].

PMID- 16630492
TI  - [Continuing tillage in our pathology field].

PMID- 16630493
TI  - [Paneth cell-rich carcinoma of stomach: report of two cases].

PMID- 16630494
TI  - [Anaplastic large cell lymphoma associated with tuberculoid granulomatous
      reaction: report of a case].

PMID- 16630495
TI  - [Goblet cell carcinoid of appendix: report of two cases].

PMID- 16630496
TI  - [Mesenchymal chondrosarcoma arising from soft tissue of pouch of Douglas: report
      of a case].

PMID- 16630497
TI  - [Recent advances in studies of tumor angiogenesis: heterogeneity of tumor
      microvascular architecture phenotype].

PMID- 16630498
TI  - [Reemphasis of pathologic study of coronary heart disease].

PMID- 16630500
TI  - [Relationship between oxidized lipoprotein, angiogenesis and human coronary
      atherosclerotic plaque stabilization].
AB  - OBJECTIVES: To analyze the relationship between oxidized low density lipoprotein
      (oxLDL), angiogenesis and stabilization of atherosclerotic plaques in human
      coronary arteries; and to investigate the role of oxLDL in creating vulnerable
      sites in atherosclerotic plaques. METHODS: Samples of coronary arteries were
      obtained at autopsies of 42 patients with acute coronary syndrome. Eighty
      randomly selected blocks were studied by immunohistochemistry using antibodies
      against oxLDL and endothelial cells (factor VIII). Computer-aided planimeter was
      used for quantitative analysis. RESULTS: In unstable plaques, percentage of
      immunoreactive areas for oxLDL was significantly higher than that in stable
      plaques. Most of the oxLDL were located in shoulder region of these plaques, as
      compared to the fibrous cap and basal regions. The details of distribution of
      oxLDL were as follows: shoulder region (20.43 +/- 3.12 for unstable plaques and
      17.65 +/- 4.22 for stable plaques), fibrous cap (4.77 +/- 2.03 for unstable
      plaque and 2.80 +/- 0.22 for stable plaques) and basal region (5.65 +/- 1.65 for
      unstable plaques and 3.22 +/- 1.02 for unstable plaques). OxLDL was also a main
      component in the lipid core. In the shoulder region, there was a significant
      positive correlation between neovascularization and oxLDL (r = 0.8247, P =
      0.000). CONCLUSIONS: The amount of oxLDL is significantly higher in unstable
      atherosclerotic plaques, especially over the shoulder region. OxLDL in coronary
      atherosclerotic plaques is thus an important factor in determining stabilization
      of the plaques. OxLDL may induce influx of inflammatory cells which subsequently
      leads to decreased plaque stabilization.

PMID- 16630501
TI  - [Clinicopathologic studies of 11 cases of primary cardiac valve tumors].
AB  - OBJECTIVE: To study the clinicopathologic features of primary cardiac valve
      tumors. METHODS: Eleven cases of primary valve tumors collected from Fuwai
      Hospital during the period from 1983 to 2005 were enrolled into the study. The
      tumors were stained with hematoxylin and eosin and Weigert-Van Gieson stain.
      Immunohistochemistry was also carried out in selected examples. RESULTS: Primary
      cardiac valve tumors were uncommon and accounted for only 3% (11/426) of all
      primary cardiac tumors. Most of them (10/11) were benign and malignancy was
      rarely encountered (1/11). The tumor subtypes included papillary fibroelastoma
      (4/11), cavernous hemangioma (4/11), glomus tumor (1/11), angiosarcoma (1/11) and
      hamartoma (1/11). Of the 11 tumors studied, 4 involved the tricuspid valve, 4
      involved the mitral valve, 2 involved the pulmonary valve and 1 involved the
      aortic valve. The diagnosis was established by preoperative echocardiography in 7
      patients. The remaining 4 cases were either misdiagnosed or undiagnosed.
      CONCLUSIONS: Preoperative diagnosis of primary cardiac valve tumors can be
      difficult due to lack of detailed information related to this group of lesions.
      Although benign cardiac valve tumors carry a good prognosis, the clinical outcome
      may be disastrous as a result of hemodynamic disturbances. Intraoperative frozen
      section examination is advisable for guiding proper surgical management.

PMID- 16630502
TI  - [Clinicopathologic and genetic studies of desmoid-type fibromatosis].
AB  - OBJECTIVE: To study the clinicopathological and genetic features of desmoid-type
      fibromatosis, and to investigate the feasibility of detecting trisomy 8 in
      formalin fixed, paraffin embedded (FFPE) tissue by fluorescence in-situ
      hybridization (FISH). METHODS: A total of 96 cases were included in this study.
      All patients had clinical information. Histopathologic and immunohistochemical
      evaluations were available in 69 cases, and ultrastructural evaluation was done
      in 2 cases of desmoid-type fibromatosis. FFPE tissue sections were available in
      20 tumors for the trisomy 8 detection by FISH. RESULTS: There were 20 male and 76
      female patients with ages ranging from 8 to 86 years (mean 35.3 years).
      Clinically, there were 44 extra-abdominal tumors, 28 abdominal wall tumors and 23
      intra-abdominal lesions mostly involving the mesentery. Most cases presented with
      nodular or funicular masses with white firm cut surfaces, measuring 0.6 to 24.0
      cm (mean 8.4 cm) in size. Histologically, desmoid-type fibromatoses showed
      longitudinal fascicles of spindle fibroblasts and myofibroblasts in a
      predominantly collagenous background. The tumor cells stained positive for
      vimentin, alpha-smooth muscle actin, desmin, and beta-catenin (47.8%, 33/69).
      Ultrastructurally, most tumor cells had features of fibroblasts, including rich
      endoplasmic reticulum and Golgi apparatus. Some tumor cells were myofibroblast
      like cells exhibiting intercellular junctions, fibronexous junctions and stress
      fibers. Trisomy 8 was detected in 6 of 20 cases of desmoid-type fibromatosis
      including 5 of the 8 recurrent tumors but only one of the 12 primary tumors. The
      latter tumor also recurred three years later. CONCLUSIONS: Desmoid-type
      fibromatosis is an intermediate (locally aggressive) tumor that occurs
      predominantly in young females. The lesion consists of fibroblasts and
      myofibroblasts with the latter showing characteristic features including stress
      fibers and fibronexous junctions. Trisomy 8 can be detected in FFPE tissue by
      FISH, and its presence serves as a useful predictor of tumor recurrence and may
      define a subtype of desmoid-type fibromatosis with high recurrence rate.

PMID- 16630503
TI  - [Prognostic significance of micropapillary pattern in pulmonary adenocarcinoma].
AB  - OBJECTIVE: To evaluate the prognostic significance of micropapillary pattern
      (MPP) in adenocarcinoma of lung. METHODS: Ninety-one consecutively excised cases
      of pulmonary adenocarcinoma, including follow-up data, were retrospectively
      studied. These tumors were divided into 2 major groups: those with MPP and those
      without MPP. The former was further subdivided according to extent of the
      micropapillary component, as follows: MPP + (constituting 1% to 10% of the
      tumor), MPP ++ (constituting 11% to 30% of the tumor) and MPP +++ (constituting
      more than 30% of the tumor). RESULTS: The overall 5-year survival rate was 64.8%.
      The 5-year survival rates were 88.9% for stage I tumors, 46.2% for stage II
      tumors, and 23.8% for stage III tumor respectively (P = 0.000). The extent of
      micropapillary component showed no correlation with tumor stage, size and 5-year
      survival rate (P = 0.065, 0.358 and 0.206, respectively). On the other hand, the
      5-year survival rate was 41.5% for patients in the MPP-positive group (number =
      41) and 84.0% for patients in the MPP-negative group (number = 50). The
      percentage of nodal metastasis in MPP-positive group was also higher than that in
      MPP-negative group (P = 0.000). In pulmonary adenocarcinoma, this characteristic
      histology correlated with tumor stage and size, but not with patient's gender and
      smoking history. Within the same stage, the 5-year survival rates of MPP-positive
      and MPP-negative groups were as follows: for stage I, 78.6% versus 92.6% (P =
      0.1548), for stage II, 30.0% versus 100% (P = 0.0598), and for stage III, 17.7%
      versus 28.6% (P = 0.4045). CONCLUSIONS: MPP in primary pulmonary adenocarcinoma,
      even when only constituting a minor component, predicts an aggressive clinical
      behavior and is associated with poor prognosis. Although it may not be an
      independent prognostic factor, presence of this histologic pattern should alert
      clinicians for more active treatment and closer follow up.

PMID- 16630504
TI  - [Correlation between matrix metalloproteinases-2 and tissue inhibitor of
      metalloproteinase-2 expression, metastatic potential and tumor angiogenesis in
      synovial sarcoma and its prognostic significance].
AB  - OBJECTIVE: To study the expression of matrix metalloproteinases (MMP)-2 and
      tissue inhibitor of metalloproteinase (TIMP)-2 in tumor cells of synovial sarcoma
      and its clinical significance. METHODS: Expression of MMP-2 and TIMP-2 in tumor
      cells of 72 cases of synovial sarcoma was studied by immunohistochemistry. The
      profile was correlated with clinicopathologic parameters, microvessel density
      (MVD) (analyzed by CD31 immunostaining) and survival rate. RESULTS: (1) There was
      a statistically significant negative correlation between expression of MMP-2 and
      TIMP-2 (r = -0.290 and P = 0.013). (2) The proportion of high MMP-2 expression to
      low TIMP-2 expression in patients with tumor metastasis was significantly higher
      than that in patients without metastasis (P = 0.010 and 0.002 respectively). (3)
      MVD of patients with high MMP-2 expression was higher than that in the low MMP-2
      expression group (P = 0.005). MVD of patients with high TIMP-2 expression was
      lower than that in the low TIMP-2 expression group (P = 0.048). (4) Low TIMP-2
      expression significantly correlated with poor prognosis of patients with synovial
      sarcoma, by univariate and multivariate survival analysis (P = 0.002 and 0.016
      respectively). CONCLUSIONS: Expression of MMP-2 and TIMP-2 correlates with
      metastatic potential and tumor angiogenesis in synovial sarcoma. Low TIMP-2
      expression often indicates poor prognosis and unfavorable clinical outcomes.

PMID- 16630505
TI  - [Effects of enhanced external counterpulsation in atherosclerosis and NF-kappaB
      expression: a pig model with hypercholesterolemia].
AB  - OBJECTIVE: To study the effects of enhanced external counterpulsation (EECP) on
      the vascular morphology, and endothelial function using experimentally induced
      hypercholesterolemic pigs. METHODS: Thirty five male pigs were randomly divided
      into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and
      17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured.
      The coronary arteries and aortas were sampled for histopathologic and
      ultrastructural examination. The NF-kappaB protein expression of porcine coronary
      arteries was investigated by immunofluorescence. RESULTS: Compared with the
      normal controls, serum cholesterol levels were significantly higher in the
      hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio
      of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%,
      versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition,
      endothelial damage and proliferation of smooth muscle cells were less severe in
      animals receiving EECP than those not. Moreover, activation and expression of NF
      kappaB also decreased significantly (P < 0.05) in animals receiving EECP.
      CONCLUSIONS: EECP improves the morphology and function of vascular endothelium,
      and retards the development and progression of atherosclerosis, likely through
      the inhibition of NF-kappaB signaling pathway.

PMID- 16630506
TI  - [Effects of caspase-3 inhibitor on the neuronal apoptosis in rat cerebral cortex
      after ischemia-reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of z-DEVD-fmk, a caspase-3 inhibitor on the
      neuronal apoptosis in ischemia-reperfusion region (IRR) of rat cerebral cortex.
      METHODS: Rats prepared by middle cerebral artery occlusion and reperfusion were
      used as the research model. The animals were divided into A group (untreated), B
      group (DMSO control) and C group (treated with z-DEVD-fmk). Before reperfusion, z
      DEVD-fmk (7 microg/kg) was injected into the ischemic side of ventriculus cerebri
      of C group rats. The expression and activation of caspase-3, expression and
      cleavage of poly (ADP-ribose) polymerase (PARP), and apoptotic neurons in the
      temporal-parietal cortex IRRs (SPAB method) of all the rats were studied using
      Western blotting, in situ apoptotic detection (TUNEL method) and
      immunohistochemistry. RESULTS: In the cerebral IRRs of A, B, C groups reperfused
      for 1 h and 24 h, the quantities of caspase-3 precursor were 16.7 +/- 3.0, 11.5
      +/- 3.0 and 47.5 +/- 3.5, and 76.1 +/- 3.5, 71.3 +/- 6.4 and 88.2 +/- 5.5,
      respectively; the caspase-3 fragments (12,000) 8.2 +/- 2.3, 9.4 +/- 1.2 and 4.3
      +/- 1.6, and 59.0 +/- 6.3, 60.5 +/- 7.2 and 17.3 +/- 2.8, respectively; the PARP
      12.6 +/- 3.0, 13.9 +/- 2.0 and 53.7 +/- 4.1, and 67.5 +/- 8.6, 61.1 +/- 6.6 and
      93.6 +/- 4.1, respectively; the PARP fragments (24,000) 6.0 +/- 0.7, 6.6 +/- 1.2,
      3.6 +/- 1.1, and 27.4 +/- 2.6, 25.8 +/- 3.2, 12.1 +/- 2.8 (relative quantity, x+/
      s); the densities of apoptotic neurons 83.3 +/- 7.5, 84.3 +/- 5.7 and 45.7 +/-
      4.0, and 197.4 +/- 11.8, 185.2 +/- 11.2 and 99.1 +/- 5.8 (cell number/0.1 mm(2),
      x+/- s). These results showed that in the cerebral IRRs of both A and B groups,
      all caspase-3 expression and activation, PARP expression and cleavage, and
      neuronal apoptosis were increased relevantly along with prolongation of the
      reperfusion time (P < 0.05 - 0.001). At each time point of the reperfusion,
      caspase-3 activation, PARP cleavage and neuronal apoptosis in the cerebral IRR of
      C group were significantly less than those of the former two groups (P < 0.05 -
      0.001). The variations of the 5 parameters of A, B and C groups correlated
      positively with one another (r = 0.630 - 0.942, P < 0.01). The cells expressing
      PARP were mainly neurons in the cerebral IRRs of all the animals, but the
      difference of their number was not distinct among the 3 groups. CONCLUSIONS: It
      is an important mechanism resulting in apoptosis of the injured neurons in the
      cerebral IRR that caspase-3 expression and activation abnormally increased by the
      reperfusion have more PARP rapidly inactivated by over-cleavage. z-DEVD-fmk may
      decrease PARP cleavage by inhibiting activity and auto-activation of caspase-3,
      and prevent the injured neurons from apoptosis.

PMID- 16630507
TI  - [Histopathologic characteristics of intestinal metaplasia in gastric mucosa of
      children].

PMID- 16630508
TI  - [Recent advances in studies of ovarian serous and mucinous borderline ovarien
      tumors].

PMID- 16630509
TI  - [Recent advance in diagnostic telepathology].

PMID- 16630510
TI  - [Pathologic diagnosis and classification of vasculitis].

PMID- 16630511
TI  - [Application of auto-stainer in routin histopathology practice].

PMID- 16630513
TI  - [Primary myxoid liposarcoma of the pericardium].

PMID- 16630514
TI  - [Cardiac schwannoma: report of a case].

PMID- 16630515
TI  - [Malignant granular cell tumor of the urinary bladder].

PMID- 16630516
TI  - [Alveolar rhabdomyosarcoma of kidney].

PMID- 16630517
TI  - [Metastases of breast cancer to female genital tract: report of 2 cases].

PMID- 16630518
TI  - [Carcinosarcoma of common bile duct: report of a case].

PMID- 16630519
TI  - The use of herbal and over-the-counter dietary supplements for the prevention of
      prostate cancer.
AB  - Having a high probability of experiencing prostate cancer during their lifetime,
      men are increasingly seeking protection against this disease with the use of over
      the-counter dietary supplements containing herbs, vitamins, or plant-derived
      biochemical agents. The use of these agents for prostate cancer prevention is
      driven by epidemiology supporting the idea that regional diets and consumption of
      specific dietary components (certain herbs, vitamins, isoflavones, and
      polyphenols) are associated with a lower risk for prostate cancer, in conjunction
      with basic research that is defining molecules within food substances that kill
      or suppress growth of cultured human prostate cancer cells. Moreover, there is a
      sense that these dietary agents lack side effects, although this assumption often
      is faulty. Unfortunately, at this time, there is insufficient clinical evidence
      to support the widespread use of these dietary supplements for chemoprevention of
      prostate cancer, although ongoing clinical trials of the most promising vitamins
      and minerals are approaching conclusion.

PMID- 16630520
TI  - New imaging techniques in prostate cancer.
AB  - Correct staging of prostate cancer at initial diagnosis, as well as accurate
      staging and tumor localization with biochemical recurrence, remains generally
      inaccurate with current imaging techniques. Newer modalities are being
      investigated to accurately identify patients with prostate cancer at different
      stages of disease. Identification of locally recurrent disease or distant
      metastasis at the time of biochemical failure after local therapy will help guide
      treatment options and avoid potentially toxic salvage therapies in patients who
      will not benefit. A review of prostate cancer imaging literature over the past 12
      months was performed to identify emerging imaging modalities that may be
      beneficial in the management of prostate cancer. Enhanced transrectal
      ultrasonography modalities, including ultrasound contrast agents, color and power
      Doppler, and elastrography, have demonstrated incremental benefit when combined
      with standard gray-scale ultrasonography to accurately target and diagnose
      prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic
      imaging, shows promise in the initial staging of prostate cancer prior to local
      therapy. The use of positron-emission tomography scan for prostate cancer remains
      to be defined, but may help delineate the site of recurrence with biochemical
      failure after local therapy. Several new imaging modalities show promise for the
      evaluation of the patient with prostate cancer. Enhanced ultrasonography
      techniques may prove to be more accurate in diagnosing prostate cancer over
      standard gray-scale ultrasonography. Accumulating evidence supports the use of
      endorectal MRI and spectroscopy to help treatment planning with either surgical
      or radiotherapeutic approaches. Although intriguing, the available data for
      positron-emission tomography in prostate cancer remains too shallow to advocate
      routine use.

PMID- 16630521
TI  - Prostate cancer detection strategies.
AB  - Prostate cancer is the most common malignancy in men and, as a result, there has
      been a nationwide emphasis on screening and detection. With the widespread use of
      the prostate-specific antigen (PSA), prostate cancer screening effectively
      detects localized prostate cancer. However, recent reports have identified a
      significant proportion of prostate cancer in men with low PSA levels. Many of
      these cancers are higher-grade malignancies. Consequently, PSA may function more
      effectively as a screening tool when applied over a continuum that is associated
      with degree of risk, rather than a binary measure. Other markers are currently
      being investigated. Ideally, a marker will identify the malignancy that is a
      clinical threat, thereby avoiding intervention for indolent disease. Prevention
      strategies may be employed for higher-risk patients, and these strategies
      eventually may be tailored to genetic or other risks.

PMID- 16630522
TI  - Dealing with non-cancerous findings on prostate biopsy.
AB  - Most prostate biopsies do not show malignancy. The proper management of non
      cancerous pathologic findings of the prostate is controversial. For this article,
      we reviewed the current literature for indications for repeat prostate biopsy
      after initial biopsies demonstrated non-cancerous prostatic tissue or benign
      prostatic hyperplasia. This review includes discussions of management of
      asymptomatic prostatitis and how it may affect prostate-specific antigen, and
      also the management of several potentially premalignant lesions such as atrophy,
      atypical small acinar proliferation, and high-grade prostatic intraepithelial
      neoplasia. There is a paucity of randomized trials in this area and, considering
      the high number of biopsies with non-malignant findings, we conclude that more
      investigation is warranted in this area.

PMID- 16630523
TI  - Management of the complications of external beam radiotherapy and brachytherapy.
AB  - External beam radiation therapy (EBRT) and brachytherapy are common treatment
      modalities for newly diagnosed prostate cancer. What complications can patients
      and physicians expect following these therapies? How are these conditions
      diagnosed and treated? In this article, we examine several of the most common
      acute and delayed complications of radiation therapy for prostate cancer. In
      addition, we discuss appropriate follow-up diagnostics for these patients and our
      suggestions for management of the main complications that may develop.

PMID- 16630524
TI  - Surgery for locally advanced disease.
AB  - Locally advanced prostate cancer is diagnosed in approximately one in four new
      cases of prostate cancer. The estimated disease-specific mortality rate resulting
      from monotherapy with either surgery or radiotherapy is a disappointing 75%. A
      multimodality treatment approach could offer more promising results. In addition,
      several key factors related to surgical treatment of locally advanced prostate
      cancer may optimize the oncologic results and minimize patient morbidity. In this
      report, we summarize some of the anatomic features and technical concepts
      associated with the surgical management of this disease and review recently
      published results of the outcomes of surgery and neoadjuvant or adjuvant
      chemohormonal therapy for locally advanced prostate cancer.

PMID- 16630525
TI  - Radiation therapy in the management of locally advanced prostate cancer.
AB  - Locally advanced prostate cancer generally refers to those patients with clinical
      stages T3-4 disease. Patients with locally advanced cancer frequently are
      included in clinical trials that examine treatment for patients at high risk for
      relapse based on presenting prostate-specific antigen, high Gleason score, or
      advanced clinical stage. There is a growing body of evidence that suggests that
      men with localized prostate cancer benefit from high-dose radiation therapy
      delivered with three-dimensional conformal radiation therapy, intensity-modulated
      radiation therapy, or proton beam therapy. Most importantly, neoadjuvant and
      adjuvant androgen-deprivation therapy have significantly improved outcomes in men
      with locally advanced or high-risk prostate cancer. Although questions remain
      regarding the optimal timing and duration of adjuvant hormonal therapy, a
      combination of long-term androgen deprivation started before radiation therapy
      and continued for 2 years represents a North American standard of care for this
      patient population.

PMID- 16630526
TI  - Primary hormone therapy for locally advanced prostate cancer.
AB  - Locally advanced prostate cancer is a treatment dilemma. As with prostate cancer
      in general, there is no clear evidence that aggressive intervention (ie, surgery
      or radiation) is superior to noninvasive interventions (eg, delayed treatment or
      androgen ablation). Because patients with locally advanced prostate cancer have a
      high risk of local and systemic recurrence, there is some argument to proceed
      with androgen ablation as the sole modality of treatment. The data using this
      approach are limited, but an understanding of the degree and duration of response
      is helpful in selecting patients for primary androgen ablation.

PMID- 16630527
TI  - The role of primary chemotherapy for prostate cancer: has the time come?
AB  - Current treatments for patients with prostate cancer generally are successful.
      However, a subset of patients identified with high-risk prostate cancer likely
      will recur after local therapy. The optimal treatment plan for these patients has
      not been determined. The search for an effective treatment for this subset of
      prostate cancer patients has focused on multi-modality therapy. Although
      chemotherapy has proven clinical and survival benefits for patients with
      metastatic disease, its role in earlier stages of the disease is being
      investigated. Current data have demonstrated that neoadjuvant or adjuvant
      chemotherapy is relatively safe and feasible. There also is emerging evidence of
      clinical benefit when early chemotherapy is combined with local treatments.
      Further investigation through prospective, randomized trials is critical to
      define the precise role of this modality in high-risk populations.

PMID- 16630528
TI  - Immunotherapy for prostate cancer.
AB  - Whereas androgen deprivation and chemotherapy have become the cornerstone of
      therapy for advanced prostate cancer, novel therapies are being developed that
      may expand upon currently available treatments. The identification of antigens
      expressed by prostate tissue and/or prostate cancer that are recognized by T
      cells or antibodies creates opportunities to develop novel immunotherapeutic
      approaches including tumor vaccines. Proteins expressed in prostate cancer
      including prostate-specific antigen, prostatic acid phosphatase, and prostate
      membrane antigen have been used as immunologic targets for immunotherapy.
      Moreover, innovations in cancer genomics and proteomics also will aid in the
      identification of immunologic targets. Emerging trials have demonstrated that
      immunotherapy may not only generate immune responses in patients, but also
      clinical responses. Future studies will be directed at capitalizing on these
      findings.

PMID- 16630529
TI  - [Takings on alive persons with the aim of donation: contributions of the law of
      bioethics of August 6, 2004].

PMID- 16630530
TI  - [Feasibility of colorectal surgery without colonic preparation. A prospective
      study].
AB  - INTRODUCTION: Mechanical bowel preparation (MBP), aimed at reducing the
      infectious complications of colorectal surgery, was considered as indispensable.
      This benefit is actually disputed. The aim of this study was to report an
      experience of colorectal surgery without MBP. MATERIALS AND METHODS: Hundred
      ninety patients without MBP and without low residue diet, who underwent
      colorectal surgery with primary anastomosis not requiring a diverting stoma were
      included. The main outcome were the rate of mortality, anastomotic leak, wound
      infection and intra-abdominal abscess. Secondary outcomes were duration of
      intravenous perfusion, nasogastric aspiration, total hospitalisation stay and
      time to realimentation. RESULTS: The procedure was performed by laparotomy
      (n=142) or laparoscopy (n=48). Forty-eight patients underwent emergency surgery.
      Ninety-two patients were operated for malignancy. The rate of mortality was 6.3%
      in correlation with the scale of AFC. The rate of anastomotic leak was 3.7%. The
      rate of specific morbidity was independent of scale of AFC on the contrary to the
      frequency of non-specific complications. The mean duration of intravenous
      perfusion and nasogastric suction were 6 days and 0.3 day. The patient had normal
      diet to the 4th day (4+/-3 days). The mean hospital stay was 13.4 days.
      CONCLUSION: The colorectal surgery without MBP may be safely performed and could
      improve the quality of life of patients in the perioperatory period.

PMID- 16630531
TI  - [Congenital cystic dilatation of bile ducts].
AB  - Congenital cystic dilatation of bile ducts is a rare condition. We report a
      retrospective study about 18 patients having congenital bile duct cysts.
      According to Todani's classification, 11 cases were type I and 7 were type V. Six
      patients from the first group had a pancreatobiliary maljunction. A total
      resection of the cyst was conducted in the type I cysts. Anatomopathologic
      examination showed an adenocarcinoma of a common bile duct cyst. In one case, a
      cancer of the gall bladder associated to a common bile duct cyst in another case.
      Three patients with segmental dilatation of intrahepatic bile ducts (type V)
      underwent liver resection. Four patients had a diffuse form, one of them was
      treated by percutaneous drainage, and in the other cases a hepatojejunostomy was
      performed. Postoperative course was complicated with acute cholangitis in these
      four cases. Percutaneous drainage and antibiotics allowed a positive outcome in
      most of the cases. In one case, secondary biliary cirrhosis occurred as a long
      term complication. Congenital cystic dilatation of bile ducts is considered to be
      a precancer state. Enterocystic anastomosis is proscribed and the resection has
      to be as complete as possible.

PMID- 16630532
TI  - [Robotic-assisted operations in digestive and endocrine surgery using Da Vinci
      system].

PMID- 16630533
TI  - Use of a dialyzable short-chain phospholipid for efficient solubilization and
      reconstitution of influenza virus envelopes.
AB  - Virosomes are reconstituted viral envelopes that can serve as vaccines and as
      vehicles for cellular delivery of various macromolecules. To further advance the
      use of virosomes, we developed a novel dialysis procedure for the reconstitution
      of influenza virus membranes that is easily applicable to industrial production
      and compatible with encapsulation of a variety of compounds. This procedure
      relies on the use of 1,2-dicaproyl-sn-glycero-3-phosphocholine (DCPC) as a
      solubilizing agent. DCPC is a short-chain lecithin with detergent-like properties
      and with a critical micelle concentration of 14 mM. DCPC effectively dissolved
      the influenza virus membranes after which the nucleocapsids could be removed by
      ultracentrifugation. The solubilized membrane components were reconstituted
      either by removal of DCPC by dialysis or by a procedure involving initial
      dilution of the solubilized membrane components followed by dialysis. Both
      protocols resulted in removal of 99.9% of DCPC and simultaneous formation of
      virosomes. Analysis of the virosome preparations by equilibrium sucrose density
      gradient centrifugation revealed co-migration of phospholipid and protein for
      virosomes produced by either method. Moreover, both virosome preparations showed
      morphological and fusogenic characteristics similar to native influenza virus.
      Size, homogeneity and spike density of the virosomes varied with the two
      different reconstitution procedures employed. The recovery of viral membrane
      proteins and phospholipids in the virosomes was found to be higher for the
      dilution/dialysis procedure than for the simple dialysis protocol. This novel
      procedure for the production of virosomes is straightforward and robust and
      allows further exploitation of virosomes as vaccines or as drug delivery vehicles
      not only in academia, but also in industrial settings.

PMID- 16630534
TI  - Polarisation, key to good localisation.
AB  - Polarisation of cells is crucial for vectorial transport of ions and solutes. In
      literature, however, proteins specifically targeted to the apical or basolateral
      membrane are often studied in non-polarised cells. To investigate whether these
      data can be extrapolated to expression in polarised cells, we studied several
      membrane-specific proteins. In polarised MDCK cells, the Aquaporin-2 water
      channel resides in intracellular vesicles and apical membrane, while the
      vasopressin-type 2 receptor, anion-exchanger 1 (AE1) protein and E-Cadherin
      mainly localise to the basolateral membrane. In non-polarised MDCK cells,
      however, Aquaporin-2 localises, besides plasma membrane, mainly in the Golgi
      complex, while the others show a dispersed staining throughout the cell.
      Moreover, while AQP2 mutants in dominant nephrogenic diabetes insipidus are
      missorted to different organelles in polarised cells, they all predominantly
      localise to the Golgi complex in non-polarised MDCK cells. Additionally, the
      maturation of V2R, and likely its missorting, is affected in transiently
      transfected compared to stably-transfected cells. In conclusion, we show that the
      use of stably-transfected polarised cells is crucial in interpreting the
      processing and the localisation of membrane targeted proteins.

PMID- 16630535
TI  - A novel matrix protein family participating in the prismatic layer framework
      formation of pearl oyster, Pinctada fucata.
AB  - Understanding the molecular composition and the formation mechanism of shell
      matrix framework is of great interest for biomineralization in mollusk shell. The
      cDNAs encoding a novel matrix protein family (KRMP) were cloned from the mantle
      of pearl oyster, Pinctada fucata. Analysis of the deduced amino acid sequences
      revealed that KRMP have a high proportion of lysine, glycine, and tyrosine, and
      their predict isoelectric points are higher than any other identified shell
      matrix protein to our knowledge. The deduced amino acid sequences of KRMP can be
      divided into three regions, including an N-terminal signal peptide, a lysine-rich
      basic region interacting with acidic proteins or CO(3)(2-), and a Gly/Tyr-rich
      region involved in the protein cross-link via quinone-tanning process. RT-PCR and
      in situ hybridization demonstrated that KRMP mRNA was specifically expressed in
      the mantle edge, involved in the prismatic layer formation. Taken together, it
      seems that KRMP is a matrix protein family participating in the framework
      formation of prismatic layer.

PMID- 16630536
TI  - Neurogenesin-1 differentially inhibits the osteoblastic differentiation by bone
      morphogenetic proteins in C2C12 cells.
AB  - Bone morphogenetic protein (BMP) antagonists regulate the pleiotropic actions of
      BMPs by binding to BMPs. We previously isolated the Neurogenesin-1 (Ng1) gene and
      found that Ng1 protein induces neuronal differentiation in the brain. In this
      study, we found that Ng1 was expressed in the primordial cells of the skeleton
      and investigated whether Ng1 protein inhibited the BMP action to induce
      osteoblastic differentiation in C2C12 myoblasts. Interestingly, Ng1 protein
      inhibited the BMP7-induced alkaline phosphatase activity while it did not inhibit
      the BMP2-induced activity. All data suggest that Ng1 protein plays an important
      role in the embryonic bone formation by differentially regulating BMPs.

PMID- 16630537
TI  - Cyt2Ba of Bacillus thuringiensis israelensis: activation by putative endogenous
      protease.
AB  - The gene cyt2Ba of Bacillus thuringiensis subsp. israelensis was cloned for
      expression, together with p20, in an acrystalliferous strain. The large hexagonal
      crystals formed were composed of Cyt2Ba, which facilitated its purification.
      Crystal solubilization in the presence of endogenous proteases (with spores and
      cell debris) enabled quick and simple procedure to obtain rather pure and active
      toxin species by cleavage between amino acid residues 34 and 35, most likely by a
      camelysin-like protease that was discovered in association with activated Cyt2Ba.
      The product of this cleavage displayed haemolytic activity comparable to that of
      exogenously activated Cyt2Ba. The sequence of this putative protease shares high
      homology with the cell envelope-bound metalloprotease (camelysin) of the closely
      related species Bacillus cereus.

PMID- 16630538
TI  - Induction of prolactin expression and release in human preadipocytes by cAMP
      activating ligands.
AB  - In addition to the pituitary, prolactin (PRL) in humans is produced at non
      pituitary sites where it acts as a cytokine. We previously reported that PRL is
      expressed and released from breast adipose explants, raising the question as to
      the dynamics of its production and its regulation. Preadipocytes were isolated
      from breast adipose tissue obtained during breast reduction. PRL expression was
      transiently increased during early preadipocyte differentiation. Both
      isoproterenol, a beta-adrenergic receptor agonist, and PACAP, pituitary adenylate
      cyclase activating peptide, increased PRL expression, and release from
      preadipocytes. This stimulation was suppressed by several protein kinase
      inhibitors, suggesting involvement of multiple signaling pathways. Transfection
      of preadipocytes with a superdistal PRL promoter/luciferase reporter revealed two
      stimulatory domains and an inhibitory domain. These data establish the
      transcriptional regulation of adipocyte PRL by the superdistal PRL promoter, its
      transient expression during adipogenesis, and the stimulatory effect of
      catecholamines and PACAP.

PMID- 16630539
TI  - Nucleic acid-binding properties of the RRM-containing protein RDM1.
AB  - RDM1 (RAD52 Motif 1) is a vertebrate protein involved in the cellular response to
      the anti-cancer drug cisplatin. In addition to an RNA recognition motif, RDM1
      contains a small amino acid motif, named RD motif, which it shares with the
      recombination and repair protein, RAD52. RDM1 binds to single- and double
      stranded DNA, and recognizes DNA distortions induced by cisplatin adducts in
      vitro. Here, we have performed an in-depth analysis of the nucleic acid-binding
      properties of RDM1 using gel-shift assays and electron microscopy. We show that
      RDM1 possesses acidic pH-dependent DNA-binding activity and that it binds RNA as
      well as DNA, and we present evidence from competition gel-shift experiments that
      RDM1 may be capable of discrimination between the two nucleic acids. Based on
      reported studies of RAD52, we have generated an RDM1 variant mutated in its RD
      motif. We find that the L119GF --> AAA mutation affects the mode of RDM1 binding
      to single-stranded DNA.

PMID- 16630540
TI  - Amelioration of amyloid load by anti-Abeta single-chain antibody in Alzheimer
      mouse model.
AB  - Parenteral immunization of transgenic mouse models of Alzheimer disease (AD) with
      synthetic amyloid beta-peptide (Abeta) prevented or reduced Abeta deposits and
      attenuated their memory and learning deficits. A clinical trial of immunization
      with synthetic Abeta, however, was halted due to brain inflammation, presumably
      induced by a toxic Abeta, T-cell- and/or Fc-mediated immune response. Another
      issue relating to such immunizations is that some AD patients may not be able to
      raise an adequate immune response to Abeta vaccination due to immunological
      tolerance or age-associated decline. Because peripheral administration of
      antibodies against Abeta also induced clearance of amyloid plaques in the model
      mice, injection of humanized Abeta antibodies has been proposed as a possible
      therapy for AD. By screening a human single-chain antibody (scFv) library for
      Abeta immunoreactivity, we have isolated a scFv that specifically reacts with
      oligomeric Abeta as well as amyloid plaques in the brain. The scFv inhibited
      Abeta amyloid fibril formation and Abeta-mediated cytotoxicity in vitro. We have
      tested the efficacy of the human scFv in a mouse model of AD (Tg2576 mice).
      Relative to control mice, injections of the scFv into the brain of Tg2576 mice
      reduced Abeta deposits. Because scFvs lack the Fc portion of the immunoglobulin
      molecule, human scFvs against Abeta may be useful to treat AD patients without
      eliciting brain inflammation.

PMID- 16630541
TI  - Induction of hypothalamic serum- and glucocorticoid-induced protein kinase-1 gene
      expression and its relation to plasma des-acyl ghrelin in energy homeostasis in
      mice.
AB  - Serum- and glucocorticoid-induced protein kinase (SGK) is a serine/threonine
      specific protein kinase that is transcriptionally regulated by serum,
      glucocorticoids, and mineral corticoids. Here, we report that fasting or obesity
      with hyperphagia increased hypothalamic SGK-1 gene expression. Hypothalamic SGK-1
      mRNA levels were proportional to daily food intake and body weights in C57BL6J
      mice, KK mice, and KKA(y) mice matched for age. Plasma des-acyl ghrelin, but not
      active ghrelin, levels were inversely proportional to daily food intake and body
      weights among these animals. The increases in hypothalamic SGK-1 gene expression
      in these animals were not accompanied by increases in plasma corticosterone
      levels. Under conditions of increased energy usage such as fasting, hypothalamic
      SGK-1 gene expression and plasma des-acyl ghrelin levels were positively
      correlated while during conditions of increased energy storage, they were
      negatively correlated. These results suggest that hypothalamic SGK-1 gene is a
      novel candidate gene involving in energy homeostasis in mice.

PMID- 16630542
TI  - Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through
      ERK activation by elevating intracellular calcium concentration.
AB  - Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in
      gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we
      examined the effect of Shh on the proliferation of a rat normal gastric mucosal
      cell line, RGM-1. RGM-1 cells express essential components of Shh receptor
      system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and
      elevated intracellular calcium concentration ([Ca2+]i). In addition, Shh as well
      as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to
      activate ERK under calcium-free culture condition. Pretreatment of cells with
      PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were
      pretreated with cyclopamine, Shh could not elevate [Ca2+]i, activate ERK or
      promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear
      accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with
      actinomycin D. These results indicate that Shh promotes the proliferation of RGM
      1 cells through an intracellular calcium- and ERK-dependent but transcription
      independent pathway via Patched/Smoothened receptor system.

PMID- 16630543
TI  - The role of ETS transcription factors in transcription and development of mouse
      preimplantation embryos.
AB  - Embryonic transcription is a crucial process for the creation of new life. To
      clarify the mechanism of embryonic transcription, we investigated the expression
      and function of the erythroblast transformation specific (ETS) domain containing
      transcription factors (TFs) during preimplantation development in mice. The
      expression levels of several ETS TFs, i.e., etsrp71, elf3, and spic, increased
      after fertilization and remained at a high level until the blastocyst stage. To
      clarify the function of these TFs, we performed gene suppression using RNA
      interference, which revealed that they were involved in regulating development to
      the blastocyst stage. Furthermore, we found that suppression of ETS TFs affected
      the transcription of eIF-1A and oct3/4 genes whose expression is regulated by
      TATA-less promoters in the embryos. These results suggest that ETS TFs function
      in the regulation of transcription with TATA-less promoters in preimplantation
      embryos, which is essential in preimplantation development.

PMID- 16630544
TI  - Hepatocyte growth factor protects human endothelial cells against advanced
      glycation end products-induced apoptosis.
AB  - Advanced glycation end products (AGEs) form by a non-enzymatic reaction between
      reducing sugars and biological proteins, which play an important role in the
      pathogenesis of atherosclerosis. In this study, we assessed AGEs effects on human
      umbilical vein endothelial cells (HUVECs) growth, proliferation and apoptosis.
      Additionally, we investigated whether hepatocyte growth factor (HGF), an anti
      apoptotic factor for endothelial cells, prevents AGEs-induced apoptosis of
      HUVECs. HUVECs were treated with AGEs in the presence or absence of HGF.
      Treatment of HUVECs with AGEs changed cell morphology, decreased cell viability,
      and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by
      AGEs in a dose- and time-dependent fashion. AGEs markedly elevated Bax and
      decreased NF-kappaB, but not Bcl-2 expression. Additionally, AGEs significantly
      inhibited cell growth through a pro-apoptotic action involving caspase-3 and -9
      activations in HUVECs. Most importantly, pretreatment with HGF protected against
      AGEs-induced cytotoxicity in the endothelial cells. HGF significantly promoted
      the expression of Bcl-2 and NF-kappaB, while decreasing the activities of caspase
      3 and -9 without affecting Bax level. Our data suggest that AGEs induce apoptosis
      in endothelial cells. HGF effectively attenuate AGEs-induced endothelial cell
      apoptosis. These findings provide new perspectives in the role of HGF in
      cardiovascular disease.

PMID- 16630545
TI  - Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin
      like protein (SLP-5) and Munc13-4 effector mechanism.
AB  - Liddle's syndrome (excessive absorption of sodium ions) and PHA-1
      (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by
      the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab
      proteins are small GTPases involved in vesicle transport, docking, and fusion.
      Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein
      protein interaction in HT-29 cells. We hereby report that Rab27a-dependent
      inhibition is associated with the GTP/GDP status as constitutively active or
      GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP
      locked inactive mutant T23N showed no effect. In order to further explore the
      molecular mechanism of this regulation, we performed competitive assays with two
      Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a
      putative priming factor for exocytosis). Both proteins eliminate negative
      modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was
      restricted to C-terminal C2A/C2B domains assigned for putative phospholipids
      binding function while the Rab27a-binding SHD motif imparted higher inhibition.
      The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to
      strongly bind it. The immunoprecipitation experiments suggest that in the
      presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC
      is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus
      minimizing its effect on channel function. These observations decisively prove
      that Rab27a inhibits ENaC function through a complex mechanism that involves
      GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5
      effector proteins.

PMID- 16630546
TI  - Reduced brain cholesterol content in arylsulfatase A-deficient mice.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by
      deficiency in arylsulfatase A (ASA). Concentrations of cholesterol and its
      metabolites were determined in ASA deficient [ASA(-/-)] mice which serve as an
      animal model of MLD. We observed a significant reduction in cholesterol content
      in the brain of adult ASA(-/-) mice when compared to wild-type controls. This was
      not due to loss of myelin, because ASA(-/-) mice do not demyelinate. Other
      cholesterol metabolites were not changed significantly in ASA(-/-) mice, except
      for an increase in lathosterol. Moreover, reduced cholesterol levels were also
      found in tissue samples from two juvenile MLD cases. Since high cholesterol
      levels are important for myelination, and various cellular processes, like
      vesicular trafficking and signal transduction, reduced cholesterol levels might
      be an important factor in the molecular pathology of MLD.

PMID- 16630547
TI  - Altered subcellular localization of ornithine decarboxylase in Alzheimer's
      disease brain.
AB  - The amyloid precursor protein can through ligand-mimicking induce expression of
      ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine
      biosynthesis. We report here the regional distribution and cellular localization
      of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and
      hippocampus of control cases, the most pronounced ODC immunoreactivity was found
      in the nucleus. In possible and definite AD the immunoreactivity had shifted to
      the cytoplasm. In cerebellum of control cases, ODC staining was found in a small
      portion of Purkinje cells, mostly in the nucleus. In AD, both possible and
      definite, the number of stained Purkinje cells increased significantly and
      immunoreactivity was shifted to the cytoplasm, even though it was still prominent
      in the nucleus. In conclusion, our study reveals an early shift of the ODC
      immunoreactivity in AD from the nuclear compartment towards the cytoplasm.

PMID- 16630548
TI  - The wbnH gene of Escherichia coli O86:H2 encodes an alpha-1,3-N
      acetylgalactosaminyl transferase involved in the O-repeating unit biosynthesis.
AB  - O-repeating unit biosynthesis is the first committed step in lipopolysaccharide
      (LPS) biosynthesis in a variety of gram-negative bacteria. The wbnH gene was
      previously proposed to encode a glycosyltransferase involved in O-repeating unit
      synthesis in Escherichia coli O86:H2 strain. In this work, we provide biochemical
      evidence to show that wbnH encodes a N-acetylgalactosaminyl transferase (GalNAcT)
      that catalyzes the transfer of GalNAc from UDP-GalNAc to the GalNAc-pyrophosphate
      lipid acceptor. WbnH activity was characterized using a synthetic acceptor
      substrate GalNAc alpha-PP-O(CH2)11-OPh. The resulting disaccharide product GalNAc
      alpha-1,3-GalNAc alpha-PP-O(CH2)11-OPh was analyzed by LC-MS and NMR
      spectroscopy. Substrate specificity study indicates that pyrophosphate and
      hydrophobic lipid moiety are structural requirements for WbnH activity. Divalent
      metal cations are not required for enzyme catalysis, suggesting WbnH belongs to
      glycosyltransferase GT-B superfamily. Our results complete the characterization
      of O86 O-unit assembly pathway, and provide the access of chemically defined O
      unit substrates for the further investigation of O-antigen biosynthetic
      mechanism.

PMID- 16630549
TI  - HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS)
      coronavirus nucleocapsid and spike proteins.
AB  - The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide
      in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N)
      and spike (S) proteins was determined by testing the proteins' ability to elicit
      a specific cellular immune response after immunization of HLA-A2.1 transgenic
      mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood
      mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences
      for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From
      HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten
      each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The
      high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays,
      with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to
      be the first identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein.
      In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes
      of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel
      peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our
      identified N317-325 and S1042-1050 CTL epitopes could induce recall responses
      when IFN-gamma stimulation of blood CD8+ T-cells revealed significant difference
      between normal healthy donors and SARS-recovered patients after those PBMCs were
      in vitro vaccinated with their cognate antigen. Our results would provide a new
      insight into the development of therapeutic vaccine in SARS.

PMID- 16630550
TI  - An investigation of genomic base distribution.
AB  - While veritable oceans of ink have been spilled over the base distributions
      within genes, the literature is virtually silent on large scale intra genomic
      base distribution. To address this issue, we have examined approximately 3400
      chromosomal sequences from approximately 2000 entire genomes-including DNA and
      RNA, single- and double-stranded, coding and non-coding genomes. For each
      sequence the mean, variance, skewness, and kurtosis for each base were computed
      along with the genome base composition. The main findings are: (1) there is no
      simple relationship between these statistics and the base composition of the
      genome, (2) in non-viral genomes, base distribution is non-uniform, (3) base
      distribution in non-eukaryotic genomes obeys a number of simple rules, (4) these
      rules are not dependent on the presence of coding sequences, (5) bacterial
      genomes in particular are unusually compliant with these rules, and (6)
      eukaryotes have a unique pattern of base distribution.

PMID- 16630551
TI  - Changes in phosphomannosyl ligands correlate with cation-dependent mannose-6
      phosphate receptors in rat liver during perinatal development.
AB  - The co-existence of two mannose-6-phosphate receptors (CD-MPR and CI-MPR) in most
      cell types is still a dilemma to be resolved. In this study, some parameters were
      measured to explore lysosomal apparatus evolution in rat liver during perinatal
      development, and establish a possible involvement of CD- and/or CI-MPR in
      lysosome maturation. Activity of four acid hydrolases was measured in the whole
      organ at different ages and it was found that N-acetyl-beta-D-glucosaminidase
      (NAG), beta-galactosidase, and beta-glucuronidase change during development,
      reaching a peak at the 10th day after birth. These results correlated with the
      expression and binding properties of CD-MPR previously reported. We also used a
      method that recognizes phosphomannosylated ligands by using purified biotinylated
      CI-MPR as a probe, and found that the highest concentrations of ligands also
      appear around the 10th day. Binding assays were also carried out, incubating
      endogenous NAG from 10-day-old and adult rats with membranes from their
      respective ages, and the results indicated that cation-dependent mannose-6
      phosphate receptor (CD-MPR) has more impact on trafficking of the enzyme at the
      10th day after birth. We concluded that lysosome maturation in the rat liver
      occurs around the 10th day after birth, and that the CD-MPR may participate in
      that event.

PMID- 16630552
TI  - Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y)
      mice.
AB  - Acetic acid (AcOH), which is a short-chain fatty acid, is reported to have some
      beneficial effects on metabolism. To test the hypothesis that feeding of AcOH
      exerts beneficial effects on glucose homeostasis in type 2 diabetes, we fed
      either a standard diet or one containing 0.3% AcOH to KK-A(y) mice for 8 weeks.
      Fasting plasma glucose and HbA1c levels were lower in mice fed AcOH for 8 weeks
      than in control mice. AcOH also reduced the expression of genes involved in
      gluconeogenesis and lipogenesis, which is in part regulated by 5'-AMP-activated
      protein kinase (AMPK) in the liver. Finally, sodium acetate, in the form of
      neutralized AcOH, directly activated AMPK and lowered the expression of genes
      such as for glucose-6-phosphatase and sterol regulatory element binding protein-1
      in rat hepatocytes. These results indicate that the hypoglycemic effect of AcOH
      might be due to activation of AMPK in the liver.

PMID- 16630553
TI  - Gene polymorphisms in the Quebec population: a risk to develop
      hypertriglyceridemia.
AB  - In Eastern Quebec, two major lipoprotein lipase (LPL) gene mutations, P207L and
      G188E, lead to complete LPL deficiency in homozygote subjects and contribute to
      elevated predisposition to hypertriglyceridemia in heterozygotes. First, we
      determined the allele frequencies of LPL (D9N, G188E, P207L, D250N, N291S, and
      S447X), APOE (C112R and C158R), PPARalpha (L162V), and PPARgamma2 (P12A) single
      nucleotide polymorphisms (SNPs) in a random-based cohort of the metropolitan
      Quebec city area. Second, we compared the LPL X447 allele frequencies observed in
      the random cohort and in a cohort of LPL P207L deficient patients. In the random
      cohort, the LPL N9 rare allele exhibited a higher prevalence than previously
      expected (p=0.0001). The LPL X447 allele frequency was lower in the patient
      cohort (Freq: 4.4%) than in the random cohort (Freq: 11.2%) (p=0.0001). These
      results reveal the importance of genetic screening for LPL gene mutations D9N and
      S447X in a population at risk to develop hypertriglyceridemia.

PMID- 16630554
TI  - Effects of heat shock protein gp96 on human dendritic cell maturation and CTL
      expansion.
AB  - We reported previously that heat shock protein gp96 and its N-terminal fragment
      were able to stimulate CTL expansion specific for a HBV peptide (SYVNTNMGL) in
      BALB/c mice. Here we characterized the adjuvant effects of gp96 on human HLA-A2
      restricted T cells. Full-length gp96 isolated from healthy human liver and
      recombinant fragments both from prokaryotic cells and eukaryotic cells were
      analyzed for their ability to stimulate maturation of human dendritic cells. It
      was found that in vitro these proteins were capable of maturating human monocyte
      derived dendritic cells (MDDC) isolated from healthy donors as well as from HBV
      positive, hepatocellular carcinoma (HCC) patients. In HLA-A2.1/Kb transgenic
      mice, gp96 and the recombinant fragments were found to augment CTL response
      specific for the HBcAg(18-27) FLPSDFFPSV peptide of hepatitis B virus.

PMID- 16630555
TI  - Simultaneous measurement of superoxide generation and intracellular Ca2+
      concentration reveals the effect of extracellular Ca2+ on rapid and transient
      contents of superoxide generation in differentiated THP-1 cells.
AB  - We invented a simultaneous measuring instrument of fluorescence and
      chemiluminescence, realizing the analysis of chronological correlation between
      change in intracellular Ca2+ concentration ([Ca2+]i) and superoxide generation. A
      human monocytic cell line, THP-1, differentiated to be neutrophil-like cells
      generated superoxide with increase in intracellular Ca2+ concentration when
      stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) whereas PMA, phorbol
      ester-stimulated superoxide response occurred without change in [Ca2+]i. The
      cells treated with TMB-8, an intracellular Ca2+ antagonist, generated superoxide
      rapidly as well as transiently with transient [Ca2+]i elevation after stimulation
      with fMLP, whereas EGTA-treated cells generated superoxide slowly as well as
      persistently with transient [Ca2+]i elevation after the stimulation. These
      results suggest that the rapid and transient contents of superoxide generation
      are specific for Ca2+ influx from the extracellular domain. Verapamil, voltage
      dependent Ca2+ channel blocker, dose-dependently inhibited fMLP-stimulated
      extracellular Ca2+ influx and superoxide generation without affecting PMA
      stimulated superoxide generation. Other channel blockers tested, nifedipine and
      diltiazem, similarly inhibited these fMLP-stimulated responses. Numerical
      analysis of the values of the response curves elucidated that TMB-8 or the
      channel blocker reveals or eliminates the same contents of superoxide generation
      by the antagonism of intracellular Ca2+ release or extracellular Ca2+ influx,
      respectively. Taking these results together, the characteristic extracellular
      Ca2+ influx essential for superoxide generation was first revealed by the
      simultaneous measurement of superoxide generation and change in [Ca2+]i.

PMID- 16630556
TI  - In vivo binding of hot pepper bZIP transcription factor CabZIP1 to the G-box
      region of pathogenesis-related protein 1 promoter.
AB  - We find that salicylic acid and ethephon treatment in hot pepper increases the
      expression of a putative basic/leucine zipper (bZIP) transcription factor gene,
      CabZIP1. CabZIP1 mRNA is expressed ubiquitously in various organs. The green
      fluorescent protein-fused transcription factor, CabZIP1::GFP, can be specifically
      localized to the nucleus, an action that is consistent with the presence of a
      nuclear localization signal in its protein sequence. Transient overexpression of
      the CabZIP1 transcription factor results in an increase in PR-1 transcripts level
      in Nicotiana benthamiana leaves. Using chromatin immunoprecipitation, we
      demonstrate that CabZIP1 binds to the G-box elements in native promoter of the
      hot pepper pathogenesis-related protein 1 (CaPR-1) gene in vivo. Taken together,
      our results suggest that CabZIP1 plays a role as a transcriptional regulator of
      the CaPR-1 gene.

PMID- 16630557
TI  - The decapping enzyme Dcp1 participates in translation termination through its
      interaction with the release factor eRF3 in budding yeast.
AB  - One of the rate-limiting steps in messenger RNA decay pathway is the 5'-cap
      cleavage of mRNAs, decapping reaction, which is conducted by the protein complex
      of Dcp1 and Dcp2. We find here that Dcp1p can interact with the release factor
      eRF3p (Sup35p) in Saccharomyces cerevisiae. Knockout of DCP1 caused not only the
      accumulation of nonsense mRNAs possibly due to the impaired decapping activity
      but also the enhancement of the read-through of nonsense codon. To examine the
      relationship between the two DCP1-knockout phenotypes, we produced DCP1 point
      mutants that lack the ability to support the translation termination.
      Interestingly, decapping activity of Dcp1p was still intact, but its interaction
      with eRF3p was abolished in the DCP1 mutants, indicating that the two functions
      originated from different entities of Dcp1p. These results suggest that the
      decapping enzyme Dcp1p may have an additional role in the translation termination
      through its interaction with eRF3p.

PMID- 16630558
TI  - Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate
      cancer LNCaP cells.
AB  - The present study reports effects of androgens and estrogens on human CYP7B1
      transcription in prostate cancer LNCaP cells. Studies with rodents have suggested
      a role for the CYP7B1 enzyme in balancing cellular hormone levels important for
      prostate growth. Little is, however, known about the regulation of human CYP7B1.
      The current study showed strong suppression of a human CYP7B1 luciferase reporter
      gene by dihydrotestosterone (DHT) in prostate cancer LNCaP cells. Also, DHT and
      overexpression of androgen receptor (AR) suppressed CYP7B1 promoter activity and
      CYP7B1-mediated catalysis in kidney-derived HEK293 cells. Effects on CYP7B1
      transcription were observed also by estrogen receptors (ER). The effects appeared
      different for different estrogens. CYP7B1 was stimulated by synthetic ER agonists
      but suppressed by 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol in
      LNCaP cells. Our data indicate an important role for CYP7B1 in balancing prostate
      hormone levels in human cells. In particular, the data suggest that androgens may
      control intraprostatic levels of estrogen via regulation of CYP7B1-mediated
      metabolism.

PMID- 16630559
TI  - Identification of DNA copy-number aberrations by array-comparative genomic
      hybridization in patients with schizophrenia.
AB  - Chromosomal abnormalities are implicated as important markers for the
      pathogenesis in patients with schizophrenia. In this study, with using bacterial
      artificial chromosome (BAC) array-based comparative genomic hybridization (CGH),
      we analyzed DNA copy-number changes among 30 patients with schizophrenia. The
      most frequent changes were partial gain of Xq23 (52%) and loss of 3q13.12 (32%).
      Other frequent gains were found in: 1p, 6q, 10p, 11p, 11q, 14p, and 15q regions,
      and frequent losses were found in: 2p, 9q, 10q, 14q, 20q, and 22q regions. The
      set of abnormal regions was confirmed by real-time PCR (9q12, 9q34.2, 11p15.4,
      14q32.33, 15q15.1, 22q11.21, and Xq23). All real-time PCR results were consistent
      with the array-CGH results. Therefore, it is suggested that array-CGH and real
      time PCR analysis could be used as powerful tools in screening for schizophrenia
      related genes. Our results might be useful for further exploration of candidate
      genomic regions in the pathogenesis of schizophrenia.

PMID- 16630560
TI  - Altered localization of amyloid precursor protein under endoplasmic reticulum
      stress.
AB  - Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant
      to the pathogenesis of Alzheimer disease. Following the amyloid cascade
      hypothesis, we therefore attempted to investigate the effects of ER stress on
      amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress
      altered the localization of amyloid precursor protein (APP) from late
      compartments to early compartments of the secretory pathway, and decreased the
      level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient
      transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta
      secretion. It was revealed that the ER stress response facilitated binding of
      BiP/GRP78 to APP, thereby causing it to be retained in the early compartments
      apart from a location suitable for the cleavages of Abeta. These findings suggest
      that induction of BiP/GRP78 during ER stress may be one of the regulatory
      mechanisms of Abeta generation.

PMID- 16630561
TI  - SHB and angiogenic factors promote ES cell differentiation to insulin-producing
      cells.
AB  - The potential use of embryonic stem (ES) cells for cell therapy of diabetes
      requires improved methods for differentiation and isolation of insulin-producing
      beta-cells. The signal transduction protein SHB may be involved in both
      angiogenesis and beta-cell development. Here we show that cells expressing the
      pancreatic endodermal marker PDX-1 appear in the vicinity of vascular structures
      in ES cell-derived embryoid bodies (EBs) cultured in vitro. Moreover,
      overexpression of SHB as well as culture of EBs in presence of the angiogenic
      growth factors PDGF or VEGF enhanced the expression of PDX-1 and/or insulin mRNA.
      Finally, expression of GFP under control of the PDX-1 promoter in EBs allowed for
      the enrichment by FACS of cells expressing PDX-1, C-peptide, and insulin as
      determined by immunofluorescence. It is concluded that SHB and angiogenic factors
      promote the development of cells expressing PDX-1 and insulin in EBs and that
      such cells can be separated by FACS.

PMID- 16630562
TI  - The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial
      trafficking.
AB  - We recently described the atypical Rho GTPases Miro-1 and Miro-2. These proteins
      have tandem GTP-binding domains separated by a linker region with putative
      calcium-binding motives. In addition, the Miro GTPases have a C-terminal
      transmembrane domain, which confers targeting to the mitochondria. It was
      reported previously that a constitutively active mutant of Miro-1 induced a
      clustering of the mitochondria. This response can be separated into two distinct
      phenotypes: a formation of aggregated mitochondria and the appearance of thread
      like mitochondria probably caused by defects in mitochondrial trafficking. The
      first GTPase domain is required for the clustering of the mitochondria, but the
      effect is not dependent on the EF-hands. Miro-2 only induces aggregation and not
      the formation of thread-like mitochondria. Moreover, we show that Miro interacts
      with the Kinesin-binding proteins, GRIF-1 and OIP106, suggesting that the Miro
      GTPases form a link between the mitochondria and the trafficking apparatus of the
      microtubules.

PMID- 16630563
TI  - Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid
      evoked apoptosis of human leukemic CEM cells.
AB  - Glucocorticoid (GC)-evoked apoptosis of T-lymphoid cells is preceded by increases
      in the intracellular Ca2+ concentration ([Ca2+]i), which may contribute to
      apoptosis. This report demonstrates that GC-mediated upregulation of the bZIP
      transcriptional repressor gene, E4BP4, is dependent on [Ca2+]i levels, and
      correlates with GC-evoked apoptosis of GC-sensitive CEM-C7-14 cells. Calcium
      chelators EGTA and BAPTA reduced [Ca2+]i levels and protected CEM-C7-14 cells
      from Dex-evoked E4BP4 upregulation as well as apoptosis. In the GC-resistant
      sister clone, CEM-C1-15, Dex treatment did not induce [Ca2+]i levels, E4BP4
      expression or apoptosis, however, the calcium ionophore A23187 restored Dex
      evoked E4BP4 upregulation and apoptosis. CEM-C7-14 cells were more sensitive to
      GC-independent increases in [Ca2+]i levels by thapsigargin, and a corresponding
      increase in E4BP4 expression and cell death, compared to CEM-C1-15 cells,
      suggesting a direct correlation between [Ca2+]i levels, E4BP4 expression, and
      apoptosis.

PMID- 16630564
TI  - The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and 
      C (SP-C) promoters in lung cells.
AB  - Surfactant protein-B (SP-B) and -C (SP-C) are small hydrophobic surfactant
      proteins that maintain surface tension in alveoli. Both SP-B and SP-C are
      regulated by a key factor, thyroid transcription factor-1 (TTF-1), in lung cells.
      Previously, we identified a 26-kDa, TTF-1-associated protein (TAP26) that was
      shown to interact with TTF-1 and enhance TTF-1-transactivated SP-B promoter
      activity. In this study, we hypothesized that TAP26 could also serve as a co
      activator of the SP-C promoter. Using the chromatin immunoprecipitation assay
      (ChIP), we demonstrated that TAP26 was not only a component of the SP-B promoter,
      but was also a component of the SP-C promoter complex in lung cells. TAP26 could
      synergistically stimulate TTF-1-activated SP-B and SP-C promoter activities in
      H441 cells (a lung adenocarcinoma cell). However, in MLE12 cells (a murine lung
      type II cell), only SP-B, but not SP-C, promoter activity was improved by TAP26
      in a concentration-dependent manner. This result indicated that the TTF-1/TAP26
      complex-activated SP-C promoter activity was already optimized in MLE12 cells and
      that the response of the SP-C promoter to the complex was different from that of
      the SP-B promoter. Via promoter mutation analysis, adjacent TTF-1 binding sites
      within the proximal promoter region of SP-C were found to be essential for TTF
      1/TAP26-enhanced SP-C promoter activity. Thus, a dimerized complex structure was
      needed for advanced promoter activity. This result also provided a molecular
      mechanism by which both the SP-B and SP-C promoters could be differentially
      regulated by the same complex.

PMID- 16630565
TI  - Cytosolic amyloid-beta peptide 42 escaping from degradation induces cell death.
AB  - Accumulating evidence suggests that intracellular amyloid-beta (Abeta) peptide
      triggers the early pathological events in Alzheimer's disease (AD). However,
      little is known about the consequence of cytosolic Abeta. In this study, we
      ectopically expressed Abeta42 in the cytoplasm of SH-SY5Y neuroblastoma cells by
      expressing a fusion protein of GFP-tagged ubiquitin and Abeta42 (GFPUb-Abeta42).
      Although GFPUb and Abeta42 are stochastically produced with the same molar ratio
      in the cytoplasm, Abeta42 was completely degraded in more than 50% of the GFPUb
      expressing cells. However, if Abeta42 was not degraded in their cytoplasm, then
      Abeta42-expressing cells underwent apoptosis. The number of Abeta42-expressing
      cells is significantly increased by the inhibition of proteasome with MG132.
      Cytosolic Abeta42 which has escaped degradation inhibits proteasome and thereby
      may accelerate the accumulation of Abeta42 and its detrimental effects. Our
      findings suggest that cells have the potential to degrade Abeta42 in their
      cytoplasm but if Abeta42 appears in the cytoplasm due to its incomplete
      degradation, it accumulates and may trigger the fatal cascade of pathology of AD.

PMID- 16630566
TI  - Interactions of recombinant prions with compounds of therapeutical significance.
AB  - The transformation of the cellular prion protein (PrP(C)) into the infectious
      form (PrP(Sc)) is implicated in the invariably fatal transmissible spongiform
      encephalopathies. To identify a mechanism to prevent the undesired PrP(C)-
      >PrP(Sc) transformation, we investigated the interactions of recombinant prion
      proteins with a number of potential therapeutic agents which inhibit the PrP(Sc)
      formation, infectivity, and the accumulation of the misfolded form. We show that
      the prion aggregates formed in the presence of six compounds have no beta
      structure, which is typical of the infectious form, and possess considerably
      higher alpha-helical content than the normal PrP(C). The investigated compounds
      stimulate the formation of alpha-helices and the destruction of beta-structure.
      They prevent the transformation of alpha-helical structure into beta-sheets.
      Probably, this is the reason for the resistance to PrP(C)-->PrP(Sc)
      transformation in the presence of these compounds. The results may be useful for
      the future therapy of neurodegenerative diseases.

PMID- 16630567
TI  - Transplantation and differentiation of donor cells in the cloned pigs.
AB  - The application of nuclear transfer technology is an interesting approach to
      investigate stem and progenitor cell transplantation therapy. If stem cells are
      used as a nuclear donor, donor cells can engraft into cloned animals without
      histocompatible problems. However, it is still uncertain whether donor cells can
      engraft to cloned animal and differentiate in vivo. To address this problem, we
      transplanted donor cells to dermal tissues of cloned pigs developed by using
      preadipocytes as donor cells. Preadipocytes are adipocytic progenitor which can
      differentiate to mature adipocytes in vitro. We showed that the donor
      preadipocytes were successfully transplanted into the cloned pigs without immune
      rejection and they differentiated into mature adipocytes in vivo 3 weeks after
      transplantation. In contrast, allogenic control preadipocytes, which can
      differentiate in vitro, did not differentiate in vivo. These results indicate
      that donor progenitor cells can differentiate in cloned animal.

PMID- 16630568
TI  - Differential expression of Hsp90 isoforms in geldanamycin-treated 9L cells.
AB  - In mammals, two major Hsp90 isoforms (Hsp90alpha and Hsp90beta) have been
      identified and found to be highly conserved among different species. However, the
      expression control of Hsp90 isoforms at both transcriptional and translational
      levels is largely unknown. Herein, we quantitatively investigate the changes in
      the total mRNA and inductive protein levels of Hsp90alpha and Hsp90beta in rat
      gliosarcoma cells treated with geldanamycin (GA). The stability of mRNA and
      protein was estimated. The translational efficiency of Hsp90 isoforms was
      measured employing in vitro translation techniques. It was found that Hsp90alpha
      was more inducible than Hsp90beta after GA treatment, whereas the hsp90alpha mRNA
      level was lower than that of hsp90beta. In addition, higher translational
      efficiency of hsp90alpha mRNA was observed, suggesting that translational control
      played an important role. Taken together, our results indicate that differential
      expression between Hsp90alpha and Hsp90beta is a consequence of both distinct
      mRNA profiles and differential translation processes.

PMID- 16630569
TI  - Molecular cloning and analysis of gonadal expression of Foxl2 in the medaka,
      Oryzias latipes.
AB  - Foxl2 is a member of the winged helix/forkhead family of transcription factors
      and is known to be involved in ovarian development in some vertebrates. To
      address the role of Foxl2 in ovarian differentiation in medaka, we isolated Foxl2
      cDNA and analyzed its expression patterns during sex differentiation. Expression
      of Foxl2 started in somatic cells surrounding germ cells in XX gonads, just after
      initiation of ovarian differentiation, and was maintained in granulosa cells
      throughout ovarian development. In the adult ovary, Foxl2 was expressed in
      previtellogenic and vitellogenic follicles, but expression ceased in
      postvitellogenic follicles. In contrast, Foxl2 mRNA could not be detected in
      testes. In addition, Foxl2 and aromatase mRNAs were co-localized in some somatic
      cells located on the ventral side of developing XX gonads. Our results suggested
      that Foxl2 was not involved in ovarian determination, but was involved in
      differentiation of granulosa cells in medaka.

PMID- 16630570
TI  - The effect of VEGF on blood vessels and blood cells during Xenopus development.
AB  - Vascular endothelial growth factor (VEGF) is known to play an essential role in
      vascular development. We have overexpressed VEGF122 or VEGF170, which are
      equivalent to mouse VEGF120 and VEGF164, in developing Xenopus embryos.
      Overexpression of VEGF170 but not VEGF122 demonstrated an absence of expression
      of hematopoietic markers alpha-globin and GATA-1 but only in the posterior
      portion of the blood island. Interestingly, strong signals of endothelial
      markers, msr, fli-1, and tie-2, were detectable in those regions, instead of
      hematopoietic markers. These results suggested both that injection of VEGF170
      resulted in disturbance of vasculogenesis in the posterior portion of the blood
      island, with excessive production of endothelial cells at the expense of blood
      cells, and that the anterior and posterior portions of the VBI may have distinct
      characteristics.

PMID- 16630571
TI  - Autocidal control of ticks by silencing of a single gene by RNA interference.
AB  - Ticks impact human and animal health worldwide and new control methods are needed
      to circumvent drawbacks of tick control by acaricide application including
      selection of drug resistant ticks and environmental pollution. Using RNA
      interference we silenced the expression of a single gene, subolesin, and produced
      ticks with diminished reproductive performance and prevented successful mating
      and production of viable offspring. We propose a sterile acarine technique (SAT)
      for reduction of tick populations by release of subolesin-silenced ticks.
      Conservation of subolesin among tick species suggests that SAT may be useful for
      control of many medically and economically important tick species.

PMID- 16630572
TI  - Bromovinyl-deoxyuridine: A selective substrate for mitochondrial thymidine kinase
      in cell extracts.
AB  - Cellular models of mitochondrial thymidine kinase (TK2) deficiency require a
      reliable method to measure TK2 activity in whole cell extracts containing two
      interfering deoxyribonucleoside kinases, thymidine kinase 1 (TK1) and
      deoxycytidine kinase. We tested the value of the thymidine analog (E)-5-(2
      bromovinyl)-2'-deoxyuridine (BVDU) as a TK2-specific substrate. With extracts of
      OSTTK1- cells containing TK2 as the only thymidine kinase and a highly specific
      TK2 inhibitor we established conditions to detect the low TK2 activity commonly
      present in cells. With extracts of TK1-proficient osteosarcoma cells and normal
      human fibroblasts we showed that BVDU, but not 1-(beta-d-arabinofuranosyl)thymine
      (Ara-T), discriminates TK2 activity even in the presence of 100-fold excess TK1.
      A comparison with current procedures based on TK2 inhibition demonstrated the
      better performance of the new TK2 assay. When cultured human fibroblasts passed
      from proliferation to quiescence TK2 activity increased by 3-fold, stressing the
      importance of TK2 function in the absence of TK1.

PMID- 16630573
TI  - Irisolidone, an isoflavone metabolite, represses JC virus gene expression via
      inhibition of Sp1 binding in human glial cells.
AB  - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease
      that results from an oligodendrocyte infection caused by the JC virus. Therefore,
      inhibiting the expression of JC virus is important for preventing and/or treating
      PML. This study found that irisolidone, an isoflavone metabolite, significantly
      inhibited the JC virus expression in primary cultured human astrocytes and glial
      cell lines. Studies examining the underlying mechanism revealed that a mutation
      of the Sp1 binding site downstream of the TATA box (Sp1-II) dramatically
      diminished the inhibitory activity of irisolidone. In addition, an irisolidone
      treatment repressed Sp1 binding to Sp1-II site, which is important for the basal
      JC virus promoter activity. The results suggest that the inhibitory effect of
      irisolidone against the JC virus may be attributed at least in part to the
      suppression of Sp1 binding to the JC virus promoter region. Therefore, the
      inhibition of the JC virus expression by irisolidone might provide therapeutic
      potential for PML caused by the JC virus.

PMID- 16630574
TI  - Difference in distribution of membrane proteins between low- and high-density
      secretory granules in parotid acinar cells.
AB  - Secretory granules (SGs) are considered to be generated as immature granules and
      to mature by condensation of their contents. In this study, SGs of parotid gland
      were separated into low-, medium-, and high-density granule fractions by Percoll
      density gradient centrifugation, since it was proposed that the density
      corresponds to the degree of maturation. The observation with electron microscopy
      showed that granules in the three fractions were very similar. The average
      diameter of high-density granules was a little but significantly larger than that
      of low-density granules. Although the three fractions contained amylase,
      suggesting that they are all SGs, distribution of membrane proteins was markedly
      different. Syntaxin6 and VAMP4 were localized in the low-density granule
      fraction, while VAMP2 was concentrated in the high-density granule fraction.
      Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2
      from the medium-density granule fraction without solubilization, but not from
      Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both
      fractions. Therefore, VAMP2 is present on the same granules, but is separated
      from syntaxin6 and VAMP4, which are expected to be removed from immature
      granules. These results suggest that the medium-density granules are
      intermediates from low- to high-density granules, and that the membrane
      components of SGs dynamically change by budding and fusion during maturation.

PMID- 16630575
TI  - Differential analysis of D-beta-Asp-containing proteins found in normal and
      infrared irradiated rabbit lens.
AB  - Although proteins are generally composed of l-alpha-amino acids, d-beta-aspartic
      acid (Asp)-containing proteins have been reported in various elderly tissues. Our
      previous study detected several d-beta-Asp-containing proteins in a rabbit lens
      derived from epithelial cell line by Western blot analysis of a 2D-gel using a
      polyclonal antibody that is highly specific for d-beta-Asp-containing proteins.
      The identity of each spot was subsequently determined by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and the Ms-Fit online
      database searching algorithm. In this study, we discovered novel d-beta-Asp
      containing proteins from rabbit lens. The results indicate that beta-crystallin
      A3, beta-crystallin A4, beta-crystallin B1, beta-crystallin B2, beta-crystallin
      B3, gamma-crystallin C, gamma-crystallin D, and lambda-crystallin in rabbit lens
      contain d-beta-Asp residues. Furthermore, the occurrence of d-beta-Asp residues
      increases with infrared ray (IR) irradiation. Additionally, some d-beta-Asp
      containing proteins only appear after IR irradiation. One such protein is the
      alpha-enolase, which shows homology to tau-crystallin.

PMID- 16630576
TI  - Substrate recognition by unsaturated glucuronyl hydrolase from Bacillus sp. GL1.
AB  - Bacterial unsaturated glucuronyl hydrolases (UGLs) together with polysaccharide
      lyases are responsible for the complete depolymerization of mammalian
      extracellular matrix glycosaminoglycans. UGL acts on various oligosaccharides
      containing unsaturated glucuronic acid (DeltaGlcA) at the nonreducing terminus
      and releases DeltaGlcA through hydrolysis. In this study, we demonstrate the
      substrate recognition mechanism of the UGL of Bacillus sp. GL1 by determining the
      X-ray crystallographic structure of its substrate-enzyme complexes. The
      tetrasaccharide-enzyme complex demonstrated that at least four subsites are
      present in the active pocket. Although several amino acid residues are crucial
      for substrate binding, the enzyme strongly recognizes DeltaGlcA at subsite -1
      through the formation of hydrogen bonds and stacking interactions, and prefers N
      acetyl-d-galactosamine and glucose rather than N-acetyl-d-glucosamine as a
      residue accommodated in subsite +1, due to the steric hindrance.

PMID- 16630577
TI  - Identification of peptide mimetics of xenoreactive alpha-Gal antigenic epitope by
      phage display.
AB  - The prevention of hyperacute rejection (HAR) triggered by interaction between the
      human natural antibody and xenoreactive antigenic epitope (Gal-alpha1, 3Gal)
      present on pig cells is the key to success in pig-to-human xenotransplantation.
      The phage display technology offers an effective strategy for screening peptides
      which can interact with the anti-Gal antibody to block alpha-Gal antigen binding
      site. Two peptide libraries, linear 7 peptide library and C7C library, were
      panned on the anti-B monoclonal antibody which has the characteristic of binding
      to the alpha-Gal antigenic epitope. After four rounds of panning, 22 positive
      phage clones were selected. Highly homologous sequence PT and STL existed among
      these selected peptides. Stachyose competitive ELISAs revealed that these
      peptides specifically bound to alpha-Gal antigen binding site. Eight peptide
      mimics of alpha-Gal antigenic epitope could inhibit the agglutination of pig red
      blood cells mediated by human sera in a dose-dependent manner. These results
      demonstrated that the selected peptides can mimic the conformational structure of
      alpha-Gal antigenic epitope and have the therapeutic potential in
      xenotransplantation.

PMID- 16630578
TI  - Mutation Glu82Lys in lamin A/C gene is associated with cardiomyopathy and
      conduction defect.
AB  - Dilated cardiomyopathy is a form of heart muscle disease characterized by
      impaired systolic function and ventricular dilation. The mutations in lamin A/C
      gene have been linked to dilated cardiomyopathy. We screened genetic mutations in
      a large Chinese family of 50 members including members with dilated
      cardiomyopathy and found a Glu82Lys substitution mutation in the rod domain of
      the lamin A/C protein in eight family members, three of them have been diagnosed
      as dilated cardiomyopathy, one presented with heart dilation. The pathogenic
      mechanism of lamin A/C gene defect is poorly understood. Glu82Lys mutated lamin
      A/C and wild type protein was transfected into HEK293 cells. The mutated protein
      was not properly localized at the inner nuclear membrane and the emerin protein,
      which interacts with lamin A/C, was also aberrantly distributed. The nuclear
      membrane structure was disrupted and heterochromatin was aggregated aberrantly in
      the nucleus of the HEK293 cells stably transfected with mutated lamin A/C gene as
      determined by transmission electron microscopy.

PMID- 16630579
TI  - Cyclosporin-A inhibits ERK phosphorylation in B cells by modulating the binding
      of Raf protein to Bcl2.
AB  - Extracellular signal-related kinase (ERK) signaling is regulated by sequential
      phosphorylation of upstream kinases including Raf. We report herein that ERK
      phosphorylation is inhibited by a short incubation with Cyclosporin-A (CsA) in
      anti-IgM activated Daudi B cells. As Bcl2, through its BH4 domain, was previously
      shown to bind both Calcineurin (Can) and Raf proteins, we hypothesized that CsA
      inhibited Can binding to Bcl2 allowing the latter to bind more Raf at the
      mitochondria thereby diverting it from activating the ERK cascade. In support of
      this less Bcl2 coprecipitated with Can heterodimer in total lysates of cells
      treated with CsA as compared to controls. In parallel, Raf1 was augmented in both
      the mitochondrial fractions of cells treated with CsA and in Bcl2
      immunoprecipitates under CsA. Finally, introduction of a Bcl2 BH4 domain into
      Daudi cells augmented ERK phosphorylation in unstimulated cells and this
      augmentation was unsensitive to CsA. We therefore suggest that CsA indirectly
      inhibited ERK activation through sequestration of Raf1, at the mitochondria.

PMID- 16630580
TI  - GABAergic miniature postsynaptic currents in septal neurons show differential
      allosteric sensitivity after binge-like ethanol exposure.
AB  - Binge-like ethanol treatment of septal neurons blunts GABAAR-mediated miniature
      postsynaptic currents (mPSCs), suggesting it arrests synaptic development.
      Ethanol may disrupt postsynaptic maturation by blunting feedback signaling
      through immature GABAARs. Here, the impact of ethanol on the sensitivity of mPSCs
      to zolpidem, zinc and 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) was
      tested. The decay phase of mPSCs showed concentration-dependent potentiation by
      zolpidem (0.03-100 microM), which was substantially blunted after ethanol
      exposure. Since zolpidem potentiation exhibited a substantial age-dependent
      increase in untreated neurons, this finding supported the idea that ethanol
      arrests synaptic development. GABAAR alpha1 subunit protein also increased with
      age in untreated neurons, paralleling enhanced sensitivity to zolpidem.
      Surprisingly, alpha1 levels were not reduced by binge ethanol even though mPSCs
      were relatively zolpidem-insensitive. Zinc (3-30 microM) decreased mPSC
      parameters in a concentration- and age-related manner with older untreated cells
      showing less inhibition. However, there was no increase in mPSC zinc sensitivity
      after binge ethanol as would be expected if a general arrest of synaptic
      maturation had occurred. 3alpha-OH-DHP (3-1000 nM) induced concentration
      dependent potentiation of mPSC decay. Although potentiation was age-independent,
      binge ethanol treatment exaggerated sensitivity to this neurosteroid. Finally,
      chronic picrotoxin pretreatment (100 microM) intended to mimic GABAAR inhibition
      from ethanol pretreatment did not significantly change mPSC modulation by
      zolpidem, zinc or 3alpha-OH-DHP. These results suggest that binge ethanol
      treatment selectively arrests a subset of processes important for maturation of
      postsynaptic GABAA Rs. However, it is unlikely that ethanol causes a broad arrest
      of postsynaptic development through a direct inhibition of GABAAR signaling.

PMID- 16630581
TI  - Absence of hearing loss in a mouse model for DFNA17 and MYH9-related disease: the
      use of public gene-targeted ES cell resources.
AB  - Multiple mouse embryonic stem (ES) cell banks expand the capability to
      characterize functions of genes implicated in human disease and to develop mouse
      models for the further understanding of disease pathology. Genetic diseases that
      result in hearing loss can provide insight into causative molecular mechanisms
      for deafness. We utilized BayGenomics, the public mouse ES cell bank, to identify
      gene-trapped ES cell lines associated with hearing loss. We identified two gene
      trapped ES cell lines specific for the non-muscle myosin heavy chain class IIA or
      myosin heavy chain IX (Myh9). Inherited mutations in the Myh9 gene have been
      linked to non-syndromic hereditary hearing impairment DFNA17 as well as 'MYH9
      related disease' characterized by macrothrombocytopenia, leukocyte inclusions,
      and in some patients deafness. Mutant Myh9 mice were derived from one of these ES
      cell lines that underwent germline transmission for in-depth otological
      examination. No homozygous mice however were identified at birth, consistent with
      recently published data describing the embryonic lethality of homozygous
      mutations in Myh9. We provide evidence that adult heterozygous Myh9 mouse inner
      ears contain half wild-type levels of Myh9 mRNA. Hearing loss however was not
      observed in heterozygous Myh9 mice in contrast to human Myh9-related diseases.
      Aged heterozygous Myh9 mice also did not show signs of cochleosaccular
      degeneration common in DFNA17. Although inheritance of Myh9 mutations in humans
      is dominant, we conclude that heterozygous loss of Myh9 is not critical to
      hearing function in mice by itself.

PMID- 16630582
TI  - Movement-related EEG indices of preparation in task switching and motor control.
AB  - Lateralized readiness potential (LRP) and time-frequency domain LRP-type
      measures, called motor-related amplitude asymmetries (MRAA), in the mu band (9-13
      Hz; mu-MRAA) and the beta band (18-26 Hz; beta-MRAA) were used to study the time
      course of preparation in a task-switching task and a response precuing task.
      Several dissociations between LRP and mu-MRAA and beta-MRAA were found. Mu-MRAA
      and beta-MRAA, but not LRP, exhibited an early and strong reversal in cortical
      lateralization when advance preparation for a switch of response hand was
      required. LRP, but not mu-MRAA or beta-MRAA, was sensitive to manipulation of the
      probability that advance preparation of response hand would be useful in a
      response precuing task. These dissociations replicate earlier findings and
      suggest that movement-related cortical rhythms and cortical potentials are
      associated with distinct preparatory component processes that differ in terms of
      level of abstraction and effort, in line with similar functional distinctions
      between component processes underlying executive control in task switching. This
      suggests that a fine-grained analysis of subprocesses involved in motor control
      may provide important guiding principles for the study and understanding of
      levels and mechanisms of cognitive control.

PMID- 16630583
TI  - Acoustic measurement: a tutorial for molecular biologists.
AB  - Although skilled in in vitro techniques, the molecular biologist may not
      understand the finer points of acoustical measurement. Measurement is necessary
      whenever the auditory system function is being measured using the auditory
      brainstem response (ABR) or distortion product otoacoustic emissions (DPOAE) or
      is being challenged by a noise exposure. While the theory of measuring an
      acoustic signal with a calibrated measuring microphone is simple, in practice, it
      can become complex. The present article presents guidelines for measuring
      acoustic stimuli which is within the abilities of a well equipped laboratory. It
      also presents a set of links for further information and some sources for
      procurement of equipment.

PMID- 16630584
TI  - GABAergic and glycinergic inhibitory mechanisms in the lamprey respiratory
      control.
AB  - The specific role of gamma-aminobutyric acid (GABA) and glycine receptors in
      respiratory rhythm generation and pattern formation was investigated in in vitro
      brainstem preparations from adult lampreys by analyzing the changes in
      respiratory activity induced by bath application of specific antagonists,
      agonists, and uptake blockers. GABAA receptor blockade by bicuculline or
      picrotoxin increased both the frequency and amplitude of respiratory bursts.
      Similar effects were observed after glycine receptor blockade by strychnine.
      Combined bath application of bicuculline and strychnine markedly increased the
      frequency and amplitude of respiratory activity. These responses were associated,
      especially at the higher concentrations of the two drugs, with the appearance of
      tonic activity and irregular, high-frequency bursts followed by transient
      depression of respiratory activity. GABAA and glycine receptor agonists
      suppressed respiratory activity. These effects were prevented by bath application
      of the corresponding specific antagonists. GABAB receptor blockade by 2
      hydroxysaclofen reduced the respiratory frequency but increased the peak
      amplitude of respiratory bursts. Activation of GABAB receptors suppressed
      respiratory activity. These responses were prevented by 2-hydroxysaclofen.
      Neither GABAC receptor agonist nor antagonist had any effects on respiration.
      Depression of both the frequency and amplitude of respiratory bursts was induced
      by blockades of GABA and glycine uptake using, respectively, nipecotic acid and
      sarcosine. The results suggest that GABA- and glycine-mediated inhibition is not
      essential for respiratory rhythm generation in the adult lamprey, although it
      appears to exert potent influences on respiratory activity and to have a role in
      maintaining a stable and regular breathing pattern.

PMID- 16630585
TI  - Antibody-mediated Hsp70 protein therapy.
AB  - Intracellular Hsp70 provides cytoprotection against a variety of stressful
      stimuli, and an effective means of increasing intracellular Hsp70 levels could
      prove beneficial in the prevention and treatment of a variety of human diseases.
      A novel protein transduction domain consisting of the single chain Fv fragment of
      an anti-DNA antibody known to penetrate into living cells and tissues, mAb 3E10,
      has recently been used to deliver functional proteins to cells. The ability of
      the single chain Fv fragment to deliver Hsp70 into living cells was tested by
      generating an Fv-Hsp70 fusion protein. Fv-Hsp70 was produced as a secreted
      protein in both COS-7 cells and the methylotropic yeast strain Pichia pastoris
      and was shown capable of penetrating into COS-7 cells and primary rat cortical
      neurons. Pre-treatment with Fv-Hsp70 protected both COS-7 cells and primary rat
      cortical neurons against subsequent exposure to hydrogen peroxide. These results
      provide the first evidence that the Fv fragment of mAb 3E10 is capable of
      delivering proteins to neurons and indicate its potential in the development of
      Hsp70 protein therapy.

PMID- 16630586
TI  - Epidermal growth factor receptor induced Erk phosphorylation in the
      suprachiasmatic nucleus.
AB  - A significant functional role for epidermal growth factor receptor (EGFR) in the
      suprachiasmatic nucleus (SCN) is suggested by the confluence of several recent
      findings: (1) EGFR is highly expressed in the SCN, (2) the EGFR ligand TGFalpha
      is expressed and apparently locally released in the SCN, and (3) EGFR activation
      local to the 3rd ventricle suppresses circadian locomotor behavior and
      drinking/feeding activities. However, it has not yet been shown that binding of
      EGFR in the SCN can activate the key signaling pathways associated with its
      function. Here, we report that EGF treatment induced Erk1/2 phosphorylation in
      the rat SCN cells. The observation indicates functional EGFR in the SCN and
      motivates further investigation of the functional role of these receptors.

PMID- 16630587
TI  - Gene therapy in the nervous system with superoxide dismutase.
AB  - Neuronal death following necrotic insults involves the generation of reactive
      oxygen species (ROS). We investigated the effects of antioxidant gene therapy on
      ROS accumulation after exposure to either sodium cyanide, kainic acid or oxygen
      glucose deprivation (OGD). Specifically, we generated herpes simplex virus-1
      amplicon vector expressing the gene for the antioxidant enzyme CuZnSOD.
      Overexpression of this gene in primary hippocampal cultures resulted in increased
      enzymatic activity of the corresponding protein. CuZnSOD significantly protected
      hippocampal neurons against sodium cyanide insult and the subsequent lipid
      peroxidation. However, it did not protect against OGD- or kainic-acid-induced
      toxicity. Moreover, CuZnSOD significantly worsened the toxicity, hydrogen
      peroxide accumulation and lipid peroxidation induced by kainic acid. As a
      possible explanation for this surprising worsening, CuZnSOD overexpression
      increased glutathione peroxidase activity in the presence of sodium cyanide but
      had no effect on catalase or glutathione peroxidase activity in the presence of
      kainic acid. Thus, cells were unlikely to be able to detoxify the excess hydrogen
      peroxide produced as a result of the CuZnSOD overexpression. These studies can be
      viewed as a cautionary note concerning gene therapy intervention against necrotic
      insults.

PMID- 16630588
TI  - A disorganized innervation of the inner ear persists in the absence of ErbB2.
AB  - ErbB2 protein is essential for the development of Schwann cells and for the
      normal fiber growth and myelin formation of peripheral nerves. We have
      investigated the fate of the otocyst-derived inner ear sensory neurons in the
      absence of ErbB2 using ErbB2 null mutants. Afferent innervation of the ear
      sensory epithelia shows numerous fibers overshooting the organ of Corti, followed
      by a reduction of those fibers in near term embryos. This suggests that mature
      Schwann cells do not play a role in targeting or maintaining the inner ear
      innervation. Comparable to the overshooting of nerve fibers, sensory neurons
      migrate beyond their normal locations into unusual positions in the modiolus.
      They may miss a stop signal provided by the Schwann cells that are absent as
      revealed with detailed histology. Reduction of overshooting afferents may be
      enhanced by a reduction of the neurotrophin Ntf3 transcript to about 25% of wild
      type. Ntf3 transcript reductions are comparable to an adult model that uses a
      dominant negative form of ErbB4 expressed in the supporting cells and Schwann
      cells of the organ of Corti. ErbB2 null mice retain afferents to inner hair cells
      possibly because of the prominent expression of the neurotrophin Bdnf in
      developing hair cells. Despite the normal presence of Bdnf transcript, afferent
      fibers are disoriented near the organ of Corti. Efferent fibers do not form an
      intraganglionic spiral bundle in the absence of spiral ganglia and appear reduced
      and disorganized. This suggests that either ErbB2 mediated alterations in sensory
      neurons or the absence of Schwann cells affects efferent fiber growth to the
      organ of Corti.

PMID- 16630589
TI  - Gastric distension enhances CCK-induced Fos-like immunoreactivity in the dorsal
      hindbrain by activating 5-HT3 receptors.
AB  - The combination of gastric distension and cholecystokinin (CCK) enhances both
      suppression of food intake and induction of c-Fos-like immunoreactivity (Fos-LI)
      in the dorsal vagal complex (DVC). Previously, we have shown that serotonin type
      3 (5-HT3) receptor mediation of suppression of food intake by CCK requires
      gastric participation. Therefore, we hypothesized that 5-HT3 receptors mediate
      CCK-induced Fos-LI in the dorsal hindbrain through a mechanism that involves
      gastric distension. To test this hypothesis, we counted Fos-LI in the DVC of
      ondansetron (1 mg/kg; 5-HT3 receptor antagonist) and vehicle-treated rats
      following gastric balloon distension (5 ml), CCK (1 microg/kg) administration, or
      CCK combined with gastric distension. Ondansetron administration attenuated DVC
      Fos-LI by CCK administration. Likewise, ondansetron attenuated Fos-LI by gastric
      distension in the DVC, specifically within the nucleus of the solitary tract
      (NTS) and area postrema (AP) nuclei. The most pronounced attenuation of
      distension-induced Fos-LI by ondansetron occurred in the NTS, particularly in the
      medial and intermedial NTS. When combined, CCK and gastric distension enhanced
      Fos-LI in the DVC greater than each treatment alone. Furthermore, ondansetron
      administration attenuated the overall DVC enhanced Fos-LI induced by CCK +
      gastric distension, in particular at the NTS and AP nuclei. We found that, within
      the mid-to-caudal regions of the NTS and AP, 5-HT3 receptors most significantly
      mediate neuronal activation by CCK + distension. In conjunction with previous
      behavioral data, these results show that gastric distension enhances CCK-induced
      neuronal activation in the DVC by activating 5-HT3 receptors.

PMID- 16630590
TI  - Age-dependent alterations in CRMP2 and CRMP4 protein expression profiles in cat
      visual cortex.
AB  - We monitored the protein expression profiles of collapsin response mediator
      protein 2 and 4 (CRMP2 and CRMP4) throughout cat primary visual area 17 at
      different postnatal ages. Single immunocytochemical stainings revealed a clear
      effect of cortical maturation on the spatial and laminar distribution profile of
      CRMP2 and CRMP4. In kittens of postnatal day 10 (P10) and 30 (P30), CRMP2 and
      CRMP4 immunoreactivity was exclusively present in fibers running perpendicular to
      the cortical surface and crossing all cortical layers, but was never found in
      neuronal cell bodies. The immunoreactive fibers were embedded in an intensely and
      homogeneously stained neuropil. In contrast, mature visual cortex
      immunocytochemistry located CRMP2 and CRMP4 in the somatodendritic compartment of
      neurons with a clear CRMP-specific lamination pattern. Similar to kitten,
      neuropil staining was clearly observed but showed a decreasing gradient from
      layer I to VI in adult area 17. Detailed analysis of cellular morphology and size
      classified the CRMP2- and CRMP4-immunopositive cells in distinct neuronal
      populations. Double labeling of CRMP2 or CRMP4 with the typical interneuron
      marker parvalbumin (PV) showed many double-labeled cells immunoreactive for CRMP4
      and PV, but not for CRMP2 and PV, corroborating the cell type-specific character
      of each CRMP. Our present results clearly illustrate that CRMP2 and CRMP4 may
      play an important role in visual cortex, possibly providing different classes of
      neurons with the potential to form a functionally meaningful network, not only
      during development, but also in adulthood, coincident with the belief that CRMPs
      are involved in neurite growth and guidance.

PMID- 16630591
TI  - Sensorimotor investigations for the Mars Gravity Biosatellite: a rotating
      spacecraft for partial gravity research.
AB  - The Mars Gravity Biosatellite will offer investigators a unique environment for
      sensorimotor research. Fifteen mice will fly for 5 weeks in low Earth orbit
      before being returned safely to the ground. Chronic 35-rpm rotation will produce
      artificial gravity equal to that on the surface of Mars (0.38 g). This
      groundbreaking flight will be the longest rodent spaceflight investigation and
      the first to explore the effects of accelerations between weightlessness and
      Earth's 1 g.

PMID- 16630592
TI  - NF-kappaB protects neurons from ischemic injury after middle cerebral artery
      occlusion in mice.
AB  - Knowledge about the molecular mechanisms of neuronal survival following ischemia
      is crucial to the development of therapeutic interventions for victims of stroke.
      Previous research in our laboratory has implicated nuclear factor-kappaB (NF
      kappaB) as contributing to neuronal survival in response to toxic or ischemic
      brain insult, with in vivo models having focused on the rat. To take advantage of
      genetic alterations available in the mouse, we utilized a murine transient
      endovascular middle cerebral artery occlusion (MCAO) model to examine the
      influence of NF-kappaB on neuronal survival. When brains were immunostained for
      the nuclear localization sequence (NLS) of the p50 subunit of NF-kappaB, a
      unilateral increase in immunoreactivity was seen, especially in pyramidal cell
      layers of the ipsilateral (stroked) hippocampus. When transgenic mice lacking p50
      were compared with non-transgenic counterparts using Fluoro-Jade, a marker for
      neurodegeneration, both the hippocampus and striatum showed enhanced
      neurodegeneration at various survival times after 1 h of MCAO. In the hippocampus
      specifically, there was an eightfold increase in Fluoro-jade staining in the p50
      knockout group vs. the non-transgenic group. Sections double stained for Fluoro
      Jade and NF-kappaB activity (using a mouse engineered with a NF-kappaB responsive
      promoter driving a LacZ gene to produce beta galactosidase) demonstrated neuronal
      degeneration only in regions sparsely showing NF-kappaB activity, and those
      demonstrating NF-kappaB activity failed to degenerate. These data provide
      evidence that NF-kappaB participates in survival signaling following temporary
      focal ischemia, and thus may represent an attractive target for pharmacologic
      activation in the treatment of stroke.

PMID- 16630593
TI  - Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: a
      possible involvement of presynaptic calcium channels.
AB  - Pb2+ is a common pollutant that causes a wide variety of detrimental effects on
      developing central nervous system, including cognitive deficit. However, the
      mechanisms of Pb2+ neurotoxicity remain to be elucidated. GABAergic synaptic
      transmission in hippocampus is implicated in learning and memory. In the present
      study, we examined the effects of Pb2+ on GABA(A)-receptor-mediated inhibitory
      postsynaptic currents (IPSCs), recorded on CA1 pyramidal neurons in rat
      hippocampal slices, using whole-cell patch clamp recording. Pb2+ significantly
      inhibited the peak amplitude of evoked IPSCs and increased paired pulse ratio. In
      addition, Pb2+ (2-50 microM) significantly diminished the frequency of
      spontaneous IPSCs in a concentration-dependent manner with an IC(50) of 7.56
      microM, without changing the amplitude of spontaneous IPSCs. However, Pb2+ (10
      microM) did not alter the frequency and amplitude of miniature IPSCs. It was
      indicated that Pb2+ impaired GABAergic synaptic transmission via a presynaptic
      mechanism, inhibiting action potential-dependent GABA release. Interestingly, the
      inhibition of spontaneous IPSC frequency induced by 10 microM Pb2+ was
      significantly attenuated either in the presence of 100 muM Cd2+ or in a low
      calcium (0.5 mM) bath. It suggested the involvement of voltage-gated calcium
      channels (VGCC) in Pb2+'s inhibition of GABA release. This study provided
      electrophysiological evidence from developing hippocampal slices to support that
      Pb2+ inhibited action potential-dependent GABA release by inhibiting presynaptic
      VGCC, which might be a mechanism for Pb2+ -induced cognitive deficit.

PMID- 16630594
TI  - ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery
      occlusion in the rat and their expression is modulated by TNF in cultured
      astrocytes.
AB  - ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes
      are a recently described group of metalloproteinases. The substrates degraded by
      ADAMTS-1, -4 and -5 suggest that they play a role in turnover of extracellular
      matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit
      anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of
      metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS
      1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to
      examine whether cytokines known to be up-regulated in stroke could alter their
      expression by astrocytes in vitro. Focal cerebral ischaemia was induced by
      transient middle cerebral artery occlusion in the rat using the filament method.
      Our results demonstrate a significant increase in expression of ADAMTS-1 and -4
      in the occluded hemisphere but no significant change in TIMP-3. This was
      accompanied by an increase in mRNA levels for interleukin (IL)-1beta, IL-1
      receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and
      protein were up-regulated by TNF in primary human astrocyte cultures. The
      increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP
      3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory
      cells and contributing to brain injury. In vitro studies suggest that the in vivo
      modulation of ADAMTS-1 and -4 may be controlled in part by TNF.

PMID- 16630595
TI  - Synthesis of galactosaminyl D-chiro-inositols.
AB  - All six isomeric D-galactosaminopyranosyl-D-chiro-inositols have been prepared by
      glycosylation of appropriate penta-O-benzyl-D-chiro-inositols. The three
      requisite protected D-chiro-inositols were prepared by SmI2-promoted pinacol
      coupling of dialdehydes derived ultimately from L-arabinose.

PMID- 16630596
TI  - Conformational analyses of mycothiol, a critical intracellular glycothiol in
      Mycobacteria.
AB  - Intracellular thiols are essential biomolecules, which play several critical
      roles in living organisms including controlling intracellular redox potential and
      acting as cofactors for several vital detoxification enzymes including S
      transferases and formaldehyde dehydrogenases. The tripeptide gamma-L-glutamyl-L
      cysteinylglycine, more commonly known as glutathione, is well known as the major
      intracellular thiol in eukaryotes and in some bacteria. However, glutathione is
      absent in the Actinomycetales bacteria such as Mycobacteria and Streptomyces and
      is believed to be replaced by 1-D-myo-inosityl-2-(N-acetyl-L-cysteinyl)amido-2
      deoxy-alpha-D-glucopyranoside, mycothiol, in these organisms. Although much is
      known about the chemistry and biochemistry of glutathione, currently much less is
      known concerning mycothiol and its properties. The structure of mycothiol is
      composed of a glycoside linkage between myo-inositol and D-glucosamine with an N
      acetyl-L-cysteine linked to the 2'-amino group of the d-glucosamine moiety.
      Mycothiol is currently of intense interest due to its essential role in the
      cellular physiology of Mycobacteria, such as Mycobacterium tuberculosis, and its
      possible role in antimycobacterial drug resistance. A detailed investigation of
      its chemistry is therefore essential in ameliorating our knowledge of this key
      glycothiol, and in shedding additional light on its biochemical role in these
      pathogenic organisms. This report presents a detailed conformational analysis of
      mycothiol utilizing a variety of force fields and stochastic search protocols.
      Cluster analyses of energetically low lying conformations have indicated the
      presence of several key conformations that are populated in the gas phase and
      with implicit water solvation. These conformations are compared to recent NMR
      studies on a derivative of mycothiol. This information should be an important
      contribution to our basic understanding of the chemistry of this glycothiol and
      critical in the design of novel inhibitors of pathogen enzymes that require it.

PMID- 16630597
TI  - Structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      alcalifaciens O29.
AB  - The O-polysaccharide was obtained by a mild acid degradation of the
      lipopolysaccharide of Providencia alcalifaciens O29. Structural studies were
      performed using sugar and methylation analyses along with 1H and 13C NMR
      spectroscopy, including two-dimensional 1H, 1H COSY, TOCSY, ROESY, H-detected 1H,
      13C HSQC and HMBC experiments. On the basis of the data obtained, the following
      structure of the branched tetrasaccharide repeating unit of the O-polysaccharide
      was established: [structure: see text].

PMID- 16630598
TI  - Synthesis of the O-linked pentasaccharide in glycoproteins of Trypanosoma cruzi
      and selective sialylation by recombinant trans-sialidase.
AB  - The mucin-like glycoproteins of Trypanosoma cruzi have novel O-linked
      oligosaccharides that are acceptors of sialic acid in the trans-sialidase (TcTS)
      reaction. The transference of sialic acid from host glycoconjugates to the mucins
      is involved in infection and pathogenesis. The synthesis of the pentasaccharide,
      beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-beta-D-Galp-(1-->6)-[beta-D-Galf-(1-
      >4)]-D-GlcpNAc and the corresponding alditol, previously isolated by reductive
      beta-elimination of the mucins, is described. The key step was the 6-O
      glycosylation of a easily accessible derivative of beta-D-Galf-(1-->4)-D-GlcpNAc
      with a beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-D-Galp donor using the
      trichloroacetimidate method. The beta-linkage was diastereoselectively obtained
      by the nitrile effect. The pentasaccharide is the major oligosaccharide in the
      mucins of T. cruzi, G strain and presents two terminal beta-D-Galp residues for
      possible sialylation by TcTS. A preparative sialylation reaction was performed
      with its benzyl glycoside and the sialylated product was isolated and
      characterized. NMR spectroscopic analysis showed that selective monosialylation
      occurred at the terminal (1-->3) linked galactopyranose.

PMID- 16630599
TI  - A comparative study of the influence of some protecting groups on the reactivity
      of D-glucosamine acceptors with a galactofuranosyl donor.
AB  - Competitive glycosylation experiments with a galactofuranosyl
      trichloroacetimidate donor were performed with glucosamine acceptors having a
      free 4-OH group and carrying different protecting groups at N-2, O-3, and O-6.
      The most reactive acceptor is the N-dimethylmaleimido 3,6-di-O-benzylated
      derivative (6c), which reacts even faster than the oxazolidinone 1a. Molecular
      orbital calculations have helped to rationalize these experimental facts in terms
      of a hard-hard reaction occurring between the donor and the acceptor.

PMID- 16630600
TI  - A concise and practical synthesis of antigenic globotriose, alpha-D-Gal-(1-->4)
      beta-D-Gal-(1-->4)-beta-D-Glc.
AB  - A concise and practical synthesis of the antigenic globotriose, alpha-D-Gal-(1-
      >4)-beta-D-Gal-(1-->4)-beta-D-Glc (13), was achieved by coupling of a
      monosaccharide donor, 3-O-allyl-2-O-benzoyl-4,6-O-benzylidene-alpha-D
      galactopyranosyl trichloroacetimidate (4) with a disaccharide acceptor, p
      methoxyphenyl 2,3,6-tri-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O
      benzoyl-beta-D-glucopyranoside (8), followed by deprotection. In spite of the
      existence of a C-2-ester substituent capable of neighboring-group participation
      in the donor, the coupling gave exclusively the alpha-linkage in satisfactory
      yield. The acceptor 8 was readily obtained from selective 3-O-benzoylation of the
      galactosyl ring of p-methoxyphenyl 2,6-di-O-benzoyl-beta-D-galactopyranosyl-(1-
      >4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranoside (7), which was prepared from p
      methoxyphenyl beta-D-lactoside (5) via isopropylidenation, benzoylation, and
      deisopropylidenation. Donor 4 was obtained from p-methoxylphenyl 3-O-allyl-2,4,6
      tri-O-benzoyl-beta-D-galactopyranoside (1) via selective 4,6-di-O-debenzoylation,
      oxidative removal of 1-O-MP, benzylidenation, and trichloroacetimidate formation.

PMID- 16630601
TI  - Novel glycosylation methods and their application to natural products synthesis.
AB  - In this short review article, several glycosylation methods that were developed
      in our laboratories, including stereocontrolled glycosylation using 2,6-anhydro
      2,6-dideoxy-2,6-dithio sugars for obtaining 2,6-dideoxy glycosides, C
      glycosylation employing unprotected sugars, environmentally benign glycosylation
      utilizing heterogeneous solid acids and ionic liquids, are recounted. In
      addition, representative and significant applications of these methods to the
      synthesis of complex natural products are described.

PMID- 16630602
TI  - A new chemical synthesis of Ascopyrone P from 1,5-anhydro-D-fructose.
AB  - The naturally occurring antioxidant Ascopyrone P (1,5-anhydro-4-deoxy-D-glycero
      hex-1-en-3-ulose, 1) was prepared from the rare sugar 1,5-anhydro-D-fructose (AF,
      3) in three steps in an overall yield of 36%. Thus, acetylation of 3 afforded the
      enolone 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulopyranose (4),
      which could be isomerised to 2,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-1
      ene-3-ulose (6). Deacetylation of 6 under mild conditions gave crystalline
      Ascopyrone P (1).

PMID- 16630603
TI  - Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D
      expression.
AB  - NKG2D is an activating receptor that is expressed on most natural killer (NK)
      cells and CD8(+) T cells. MHC class I-related chain A(MICA) and UL16-binding
      protein (ULBP) 1, 2, and 3 are well-known ligands for NKG2D. Human gastric cancer
      cell lines, SNU216 and SNU638 cells which expressed UL16-binding protein (ULBP)
      were susceptible to NK cells in a NKG2D-dependent manner. However, SNU484 and
      SNU620 cells which had no ULBP on their surface were resistant to NK cells. ULBP
      1, 2, and 3 are glycosylphosphatidylinositol (GPI)-anchored proteins which are
      sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC). When SNU620
      cells were treated with U73122, an inhibitor of PI-PLC, the surface expression of
      ULBP was elevated with increased NK susceptibility. Pre-incubating NK cells with
      culture supernatants of SNU620 or SNU638 cells, which contained soluble ULBP
      protein, reduced NK cell activity by decreasing surface expression of NKG2D in NK
      cells. Furthermore, recombinant ULBP-Fc induced the down-regulation of NKG2D
      expression in NK cells. Taken together, down-regulation of NKG2D by soluble ULBP
      provides a potential mechanism by which gastric cancer cells escape NKG2D
      mediated attack by the immune cells.

PMID- 16630604
TI  - Impact of angiotensin-converting enzyme inhibition on renal cortical
      nitrotyrosine content during increased extracellular glucose concentration.
AB  - OBJECTIVES: Experiments evaluated the hypothesis that angiotensin-converting
      enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT)
      production in the renal cortex. DESIGN AND METHODS: Rats were untreated (UNTR, n
      = 6) or received the ACE inhibitor enalapril (20 mg/kg/day; ENAL, n = 6) for 2
      weeks. Renal cortical slices were incubated for 90 min in media containing 5
      (normal) or 20 mmol/L (high) glucose. Superoxide anion (O2*-) and nitrate +
      nitrite (NO(X)) levels were measured in the media. Superoxide dismutase (SOD)
      activity and NT content were measured in the tissue homogenate. RESULTS: In the
      UNTR group, high glucose increased O2*- and NO(X) production by the renal cortex
      (P < 0.05 vs. normal glucose). Likewise, NT content and SOD activity of the renal
      cortex augmented (P < 0.05 vs. normal glucose). In the ENAL group, O2*-
      production and NT content were glucose-insensitive, but high glucose exerted an
      exaggerated impact on NO(X) production and SOD activity (P < 0.01 vs. UNTR in
      high glucose). CONCLUSION: Accelerated NT content in the renal cortex during high
      glucose conditions was prevented by ACE inhibitor treatment. It was suggested
      that, apart from its anti-hypertensive effect, the mechanism of suppressed NT
      degradation in the renal cortex by the ACE inhibitor enhances both O2*-
      degradation per se and antioxidative effects including SOD activation.

PMID- 16630605
TI  - Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large
      anticoagulant clinic cohort.
AB  - OBJECTIVES: To assess allele frequency and genotype distribution of CYP2C9
      polymorphisms in patients (n = 189) attending an anticoagulant clinic in
      comparison to control patients (n = 177) and also to assess if the patients with
      variant genotypes require lower doses of warfarin. METHODS: Genotyping of the
      common CYP2C9 variants *2 and *3 was carried out by multiplexed PCR-RFLP while
      the *5 and *6 allele variants were genotyped by singleton PCR-RFLP. DNA
      sequencing was used to confirm genotype in all specimens with *3, *4 and *6
      alleles. RESULTS: CYP2C9 allele frequencies in patients were 0.81 for *1, 0.11
      for *2 and 0.08 for *3, compared to 0.88, 0.08 and 0.04, respectively, in
      controls. Patients with *1/*3 and *X/*X (where *X is *2 or *3) genotypes required
      32 to 67% less warfarin in comparison to patients with the normal *1/*1 genotype.
      Other alleles were observed in less than 1% of subjects. CONCLUSIONS: Allele
      frequencies and genotypes for CYP2C9*2 and *3 variants in patients on warfarin
      are not statistically different from controls whether or not they are stratified
      for ethnicity. Less common genotypes (*4, *5, *6) do not contribute significantly
      to warfarin sensitivity among patients attending a routine anticoagulation
      clinic. CYP2C9 genotype predicts warfarin dosage even in an uncontrolled,
      retrospective survey of unselected patients on warfarin therapy.

PMID- 16630607
TI  - Oocyte and egg organization in the patellogastropod Lottia and its bearing on
      axial specification during early embryogenesis.
AB  - In the basal gastropod Lottia, the apical region of the oocyte is normally the
      site where the meiotic apparatus attaches and polar body formation occurs
      following fertilization. This site marks the animal-vegetal axis of the egg. A
      stereotypical cleavage pattern is organized, and the segregation of developmental
      potential occurs along this axis during early development. The segregation of
      developmental potential is a relatively late event and probably does not start
      until after cleavage begins. By compressing oocytes during the process of
      germinal vesicle breakdown, the position where the meiotic apparatus attaches to
      the cell membrane can be altered so that it no longer corresponds to the apical
      end of the oocyte. This new site of polar body formation sets up a new animal
      vegetal axis that organizes cleavage and the segregation of developmental
      potential. The timing of animal-vegetal axis specification in Lottia is much
      later than it is in derived gastropods with a precocious specification of the D
      quadrant.

PMID- 16630606
TI  - BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and
      patterning.
AB  - The mesenchyme of the developing vertebrate limb responds to inductive signals,
      giving rise to skeletal elements that define limb shape and size. Several signals
      emanate from the limb ectoderm and in particular from the specialized epithelium
      of the apical ectodermal ridge (AER), including three members of the bone
      morphogenetic protein (BMP) family of signaling molecules, BMP2, BMP4 and BMP7.
      Using the Cre/loxP system in mice, we rendered limb bud mesenchyme insensitive to
      BMP signals through the type I receptor, BMPR-IA. Conditional mutants had
      shortened limbs and almost complete agenesis of the autopod because of reduced
      cell proliferation. Reduced expression of downstream BMP signaling targets, Msx1,
      Msx2 and gremlin in the distal mesenchyme (progress zone) correlated with
      decreased levels of cyclin D1 and Wnt5a. Ectopic anterior activation of sonic
      hedgehog (SHH) signaling and Hox expression revealed alterations in anterior
      posterior (AP) patterning. Abnormal localization of Lmx1b-expressing cells in the
      ventral mesenchyme, along with histological alterations and an abnormal
      melanization pattern of the limb, indicate altered dorsal-ventral (DV)
      boundaries. These findings suggest that signaling through BMPR-IA in limb
      mesenchyme is essential for distal outgrowth and also influences AP and DV
      patterning.

PMID- 16630608
TI  - The nitric oxide synthesis/pathway mediates the inhibitory serotoninergic
      responses of the pressor effect elicited by sympathetic stimulation in diabetic
      pithed rats.
AB  - We investigated the involvement of the nitric oxide pathway in the inhibitory
      mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by
      stimulation of sympathetic vasopressor outflow in diabetic pithed rats. Diabetes
      was induced in male Wistar rats by a single s.c. injection of alloxan. Four weeks
      later, the animals were anaesthetized, pretreated with atropine, and pithed.
      Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5,
      1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. The
      inhibition of electrically induced pressor responses by 5-HT (10 microg/kg/min)
      in diabetic pithed rats could not be elicited after i.v. treatment with 1H
      [1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microg/kg), a guanylyl cyclase
      inhibitor, or N-omega-L-Arginine methyl ester hydrochloride (L-NAME) (10 mg/kg),
      a nitric oxide synthase (NOS) inhibitor. The inhibitory effect produced by
      infusion of the selective 5-HT(1A) receptor agonist 8
      hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (20 microg/kg/min) was
      abolished in the presence of ODQ (10 microg/kg), or L-NAME (10 mg/kg) in diabetic
      pithed rats. The administration of L-Arginine (100 mg/kg) 30 min after L-NAME
      reproduced the inhibitory effect caused by 5-HT (10 microg/kg/min) and 8-OH-DPAT
      (20 microg/kg/min) on the electrically induced pressor responses, whereas in the
      presence of D-Arginine (100 mg/kg)+L-NAME the 5-HT or 8-OH-DPAT inhibitory effect
      on the pressor responses was abolished. In conclusion, in diabetic pithed rats,
      the inhibition produced by prejunctional 5-HT(1A) activation on electrically
      induced sympathetic pressor responses is mediated by the NO synthesis/pathway.

PMID- 16630609
TI  - Modulation of human TRPV1 receptor activity by extracellular protons and host
      cell expression system.
AB  - The transient receptor potential vanilloid 1 (TRPV1) receptor is a ligand-gated
      cation channel that can be activated by capsaicin, heat, protons and cytosolic
      lipids. We compared activation of recombinant human TRPV1 receptors stably
      expressed in human 293 cells, derived from kidney embryonic cells, and in human
      1321N1 cells, derived from brain astrocytes. Cellular influx of calcium was
      measured in response to acid, endovanilloids (N-arachidonoyl-dopamine, N-oleoyl
      dopamine and anandamide), capsaicin and other traditional vanilloid agonists
      under normal (pH 7.4) and acidic (pH 6.7 and 6.0) assay conditions. The host cell
      expression system altered the agonist profile of endogenous TRPV1 receptor
      agonists without affecting the pharmacological profile of either exogenous TRPV1
      receptor agonists or antagonists. Our data signify that the host cell expression
      system plays a modulatory role in TRPV1 receptor activity, and suggests that
      activation of native human TRPV1 receptors in vivo will be dependent on cell
      specific regulatory factors/pathways.

PMID- 16630610
TI  - Cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR,
      CHK2, and BRCA1.
AB  - Topoisomerase II is essential for cell proliferation and survival and has been a
      target of various anticancer drugs. ICRF-193 has long been used as a catalytic
      inhibitor to study the function of topoisomerase II. Here, we show that ICRF-193
      treatment induces DNA damage signaling. Treatment with ICRF-193 induced G2 arrest
      and DNA damage signaling involving gamma-H2AX foci formation and CHK2
      phosphorylation. DNA damage by ICRF-193 was further demonstrated by formation of
      the nuclear foci of 53BP1, NBS1, BRCA1, MDC1, and FANCD2 and increased comet tail
      moment. The DNA damage signaling induced by ICRF-193 was mediated by ATM and ATR
      and was restricted to cells in specific cell cycle stages such as S, G2, and
      mitosis including late and early G1 phases. Downstream signaling of ATM and ATR
      involved the phosphorylation of CHK2 and BRCA1. Altogether, our results
      demonstrate that ICRF-193 induces DNA damage signaling in a cell cycle-dependent
      manner and suggest that topoisomerase II might be essential for the progression
      of the cell cycle at several stages including DNA decondensation.

PMID- 16630611
TI  - The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and
      Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics.
AB  - Binding partners for the Cdc42 effector CIP4 were identified by the yeast two
      hybrid system, as well as by testing potential CIP4-binding proteins in
      coimmunoprecipitation experiments. One of the CIP4-binding proteins, DAAM1, was
      characterised in more detail. DAAM1 is a ubiquitously expressed member of the
      mammalian diaphanous-related formins, which include proteins such as mDia1 and
      mDia2. DAAM1 was shown to bind to the SH3 domain of CIP4 in vivo. Ectopically
      expressed DAAM1 localised in dotted pattern at the dorsal side of transfected
      cells and the protein was accumulated in the proximity to the microtubule
      organising centre. Moreover, ectopic expression of DAAM1 induced a marked
      alteration of the cell morphology, seen as rounding up of the cells, the
      formation of branched protrusions as well as a reduction of stress-fibres in the
      transfected cells. Coimmunoprecipitation experiments demonstrated that DAAM1
      bound to RhoA and Cdc42 in a GTP-dependent manner. Moreover, DAAM1 was found to
      interact and collaborate with the non-receptor tyrosine kinase Src in the
      formation of branched protrusions. Taken together, our data indicate that DAAM1
      communicates with Rho GTPases, CIP4 and Src in the regulation of the signalling
      pathways that co-ordinate the dynamics of the actin filament system.

PMID- 16630612
TI  - Phospholipase D from photoreceptor rod outer segments is a downstream effector of
      RhoA: evidence of a light-dependent mechanism.
AB  - Photoreceptor cells contain rod outer segments (ROS) which are specialized light
      sensitive organelles. The biological function of ROS is to generate a
      photoresponse, which occurs via the classic transducin-mediated pathway.
      Moreover, ROS undergo light-regulated membrane turnover and protein translocation
      whose mechanisms have not been fully elucidated to date. Phospholipase D (PLD) is
      a key enzyme involved in lipid signal transduction and membrane trafficking. We
      have previously reported that PLD activity is present in purified ROS (Salvador,
      G.A., Giusto, N.M., 1998. Characterization of phospholipase D activity in bovine
      photoreceptor membranes. Lipids 33, 853-860). We now demonstrate that ROS PLD
      activity is enhanced by phosphatidylinositol bisphosphate (PIP2) and cytosolic
      factors in a GTP dependent-manner. Western blot analysis demonstrates the
      presence of PLD1 isoform in purified ROS. In ROS obtained from dark-adapted
      retinas (DROS), PIP2-dependent PLD activity was higher than that observed in ROS
      obtained from light-adapted retinas (LROS). In addition, experiments carried out
      in the presence of C3 toxin inhibited PLD activity from DROS whereas pertussis
      toxin did not affect the enzyme activity. Western blot analysis demonstrates the
      presence of RhoA, a PLD upstream-regulator. Moreover, RhoA levels were higher in
      DROS with respect to those in LROS. The present study reports evidence of the
      involvement of the small G-protein, RhoA, in ROS PLD regulation. Our data
      strongly suggest that RhoA regulates ROS PLD activity under a light-dependent
      mechanism.

PMID- 16630613
TI  - Thymosin beta4 inhibits benzalkonium chloride-mediated apoptosis in corneal and
      conjunctival epithelial cells in vitro.
AB  - Thymosin beta-4 (Tbeta(4)) is known to promote ocular wound healing, to decrease
      ocular inflammation, and to have anti-apoptotic effects on corneal epithelium. In
      this study, the effect of Tbeta(4) on the survival of human ocular surface
      epithelial cells exposed to benzalkonium chloride (BAK) was measured. Human
      conjunctival epithelial cells (HC0597) or human corneal epithelial cells (HCET)
      were treated with 0%, 0.001%, 0.01%, or 0.1% BAK for 15 min. After 3 or 24h of
      recovery in culture medium containing 1 microg/ml Tbeta(4), a dosage that has
      been demonstrated effective in several published studies, DNA synthesis was
      measured using a colorimetric BrdU incorporation assay. Both conjunctival and
      corneal epithelial DNA synthesis was inhibited by BAK in a dose-dependent manner.
      Tbeta(4) did not protect the epithelial cells from BAK-induced inhibition of
      proliferation. To assess the ability of Tbeta(4) to prevent apoptosis, epithelial
      cells were treated with 0.01% BAK+Tbeta(4) and cell death was measured using a
      colorimetric assay. BAK-induced apoptosis increased throughout the duration of
      the assay, which was carried out to 5 days in culture. Treatment of HC0597 cells
      with Tbeta(4) significantly inhibited the apoptosis shown to be initiated by BAK.
      Treatment of non-transformed human corneal epithelial cells (HCEC) with Tbeta(4)
      also significantly inhibited the apoptosis shown to be initiated by BAK at later
      times in culture. Ocular solutions containing BAK as a preservative are typically
      used for extended periods of time. This study suggests that Tbeta(4) may be able
      to overcome the apoptotic side effect of BAK, and may be a useful additive to
      solutions containing this preservative.

PMID- 16630614
TI  - The potential of endogenous neuronal replacement in developing cerebral cortex
      following hypoxic injury.

PMID- 16630615
TI  - Galanin expressed in the excitatory fibers attenuates synaptic strength and
      generalized seizures in the piriform cortex of mice.
AB  - The neuropeptide galanin is considered to be an endogenous antiepileptic agent,
      presumably acting via inhibition of glutamate release. Previously, we have
      demonstrated that in mice ectopically overexpressing galanin in cortical and
      hippocampal neurons, particularly in granule cells and their axons, the mossy
      fibers, hippocampal kindling epileptogenesis is suppressed and is associated with
      attenuated frequency facilitation in mossy fiber-CA3 cell synapses. We
      hypothesized that changes in synaptic transmission might occur also in other
      excitatory synapses of the galanin overexpressing (GalOE) mouse, contributing to
      seizure suppression. Lateral olfactory tract (LOT) synapses, formed by axons of
      olfactory bulb (OB) mitral cells and targeting piriform cortex (PC) pyramidal
      cells, ectopically express galanin in GalOE mice. Using whole-cell patch-clamp
      recordings, we found that excitatory synaptic responses recorded in PC pyramidal
      cells during high frequency stimulation of the LOT were attenuated in GalOE mice
      as compared to wild-type controls. This effect was mimicked by bath application
      of galanin or its agonist galnon to wild-type slices, supporting the notion of
      ectopic galanin action. Since the high frequency activation induced in vitro
      resembles epileptic seizures in vivo, we asked whether the observed synaptic
      inhibition would result in altered epileptogenesis when animals were kindled via
      the same synapses. In male GalOE mice, we found that the latency to convulsions
      was prolonged, and once animals had experienced the first stage 5 seizure,
      generalized seizures were less sustainable. These data indicate that the PC is a
      possible target for epilepsy treatment by ectopically overexpressing galanin to
      modulate seizure activity.

PMID- 16630616
TI  - Carbohydrate based vaccines.
AB  - In the past decades, a gradual increase in the resistance to antibiotics has been
      observed, leading to a serious thread for successful treatment of bacterial
      infections. This feature in addition to difficulties in developing adequate drugs
      against (tropical) diseases caused by parasites has stimulated the interest in
      vaccines to prevent infections. In principle, various types of cell surface
      epitopes, characteristic for the invading organism or related to aberrant growth
      of cells, can be applied to develop vaccines. The progress in establishing the
      structure of carbohydrate immuno-determinants in conjunction with improvements in
      carbohydrate synthesis has rendered it feasible to develop new generations of
      carbohydrate-based vaccines.

PMID- 16630617
TI  - Using specific antisera to neutralize ACTH in sturgeon: a method for manipulating
      the interrenal response during stress.
AB  - Interrenal function and the magnitude of the stress response were assessed in
      green sturgeon (Acipenser medirostris) passively immunized with antisera directed
      against adrenocorticotropic hormone (ACTH). The nucleotide sequence encoding ACTH
      was determined using reverse transcriptase polymerase chain reaction (RT-PCR). We
      identified two isoforms of ACTH that differ at a single site (position 26) in the
      39 AA peptide. Both forms of green sturgeon ACTH (gsACTH1-39) display 100%
      homology with both sequences of white sturgeon ACTH (wsACTH1-39). The N-terminal
      portion of gsACTH also shares absolute identity with the comparable portion of
      human ACTH (hACTH). However, we identified considerable sequence divergence in
      the C-terminal domain between gsACTH and hACTH. Species-specific anti-ACTH sera
      were generated by vaccinating sheep against the C-terminal portion of gsACTH
      (gsACTH26-39). The peptide was covalently linked to a carrier protein (keyhole
      limpet-hemocyanin [KLH]) to further enhance its immunogenicity. The anti-gsACTH
      sera recognized gsACTH1-39 and the immunogenic peptide (gsACTH26-39), but did not
      interact with hACTH1-39. To assess the impact of the antisera, fish were
      passively immunized with anti-gsACTH26-39 sera or anti-KLH sera and challenged
      with a hACTH1-39 injection on day 1 followed by a 1-min air emersion stressor on
      day 2. The magnitude and duration of the secretory response induced by hACTH did
      not differ (P > .05) between groups. Conversely, the magnitude of cortisol
      secretion induced by air emersion was significantly attenuated (P < .05) in fish
      passively immunized against gsACTH26-39. Collectively, these data demonstrate
      that the targeted antisera used in this study can discriminate between mammalian
      and green sturgeon ACTH and moderate the in vivo response to a stressor.

PMID- 16630618
TI  - Ontogeny of the endocrine pancreatic cells of the gilthead sea bream, Sparus
      aurata (Teleost).
AB  - The development of the gilthead sea bream, Sparus aurata, endocrine pancreas was
      studied from hatching to 114 days, using immunocytochemical techniques. Bonito
      insulin (INS)-, synthetic somatostatin-14 (SS-14)-, salmon somatostatin-25 (SS
      25)-, mammalian somatostatin-28 (1-12) (SS-28)-, porcine glucagon (GLU)-,
      glucagon-like peptide-1 (1-19) (GLP-1)-, synthetic porcine peptide tyrosine
      tyrosine (PYY)-, and neuropeptide Y (NPY)-like immunoreactivities were
      demonstrated. The different types of endocrine cells appear at distinct stages of
      development and differ in their arrangement. The coexistence of INS and SS-25
      immunoreactivities was demonstrated in the cells of one strand or primordial cord
      and a primordial islet that appeared close to the dorsal epithelium of the
      anterior region of the undifferentiated gut or next to the gut at hatching and
      one day after hatching, respectively. INS- and SS-25- immunoreactive (ir) cells
      were located in the core and at the periphery of the single islet found in 2-day
      old larvae, while SS-28-ir cells were found in the single islet in 4- to 11-day
      old larvae. GLU/GLP-1-ir cells were located next to the outer SS-25-ir cells in
      the single islet of 12- and 16-day-old larvae. SS-14/SS-25- and SS-14/SS-28-ir
      cells were detected in the outer region and in the inner area of the single
      islet, respectively, in 17- to 23-day-old larvae. One big islet and several small
      islets and isolated or clustered cells next to the pancreatic duct were present
      in 24- and 25-day-old larvae. The islets were similar in cell composition to the
      single islet seen in the previous stage, while the isolated and grouped cells
      showed the coexistence of INS and diverse SSs immunoreactivities. Nerve fibers
      showing PYY immunoreactivity were identified in the islets from 17 days onwards.
      In 30- to 44-day-old larvae, GLU and NPY immunoreactivities coexisted in a few
      cells at the periphery of some small islets. PYY-ir cells were first detected at
      day 51. One big islet, several intermediate islets and numerous small islets were
      present from 51-day-old-larvae to juveniles. GLU was colocalized with PYY and NPY
      in a few cells in a small peripheral area in the big islet and a few intermediate
      islets. The outer region of small islets and other intermediate islets showed the
      complete coexistence of GLU, PYY, and NPY.

PMID- 16630619
TI  - Identification of immunoreactive plasma and stomach ghrelin, and expression of
      stomach ghrelin mRNA in the bullfrog, Rana catesbeiana.
AB  - In this study, we established a radioimmunoassay (RIA) specific for ghrelin from
      the bullfrog Rana catesbeiana using a novel antibody raised against the C
      terminal amino acid sequence of bullfrog ghrelin [13-28]. We also examined the
      distribution of ghrelin-producing cells in the stomachs of bullfrogs using this
      antibody and a cRNA probe specific for the bullfrog ghrelin gene. Ghrelin levels
      in plasma and stomach extracts were approximately 150 fmol/ml and 83-135 fmol/mg
      wet tissue, respectively. Reverse-phase high performance liquid chromatographic
      analysis, combined with bullfrog ghrelin RIA, revealed that ghrelin
      immunoreactivity in the stomach was composed of non-acylated ghrelin (des-acyl
      ghrelin) and several acylated forms of ghrelin bearing different fatty acid
      modifications, which could induce increases in intracellular Ca2+ in cells
      expressing the rat GH secretagogue receptor. In the stomach, the major storage
      form was acylated ghrelin. In bullfrog plasma, however, the majority of ghrelin
      immunoreactivity was des-acyl ghrelin and C-terminal fragments of frog ghrelin.
      Acylated ghrelin forms comprised only minor peaks. Ghrelin-immunopositive and
      ghrelin mRNA-expressing cells were observed within the mucosal layer of the
      stomach. Following starvation, significant increases in plasma ghrelin levels and
      stomach ghrelin mRNA levels were observed as early as 10 days after starvation.
      These results indicate that ghrelin is present in the stomach and plasma of the
      bullfrog, which can be detected with our novel antibody. Interestingly, the
      primary storage form of ghrelin in the stomach differed from the circulating form
      dominating in the plasma. Furthermore, increases in ghrelin levels in plasma and
      mRNA levels in the stomach after starvation suggest the possible involvement of
      ghrelin in energy homeostasis in the bullfrog.

PMID- 16630620
TI  - Circulating levels of cholecystokinin and gastrin-releasing peptide in rainbow
      trout fed different diets.
AB  - Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal
      peptides thought to be important regulators of intake and digestion of food in
      vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP
      were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of
      homologous radioimmunoassays, and the hormonal levels assessed in relation to
      dietary lipid:protein ratio and food intake. Fish were acclimated to either a
      high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high
      lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio
      dense lead-glass beads were included in the diets for assessment of feed intake.
      Fish were terminally sampled for blood and stomach contents prior to feeding at
      time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial
      elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed
      the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL
      diet. Plasma CCK levels were not affected by the amount of food ingested. GRP
      levels in plasma were not influenced by sampling time, diet, or feed intake. The
      results indicate that the endocrine release of gastrointestinal CCK is increased
      during feeding and may be further influenced by the dietary lipid:protein ratio
      in rainbow trout. Plasma GRP levels, on the other hand, appear not to be
      influenced by feeding or diet composition.

PMID- 16630621
TI  - Syndesmotic screw fixation in Weber C ankle injuries--should the screw be removed
      before weight bearing?
AB  - OBJECTIVE: To compare the outcomes of Weber C ankle fractures treated with
      syndesmotic screw fixation where the screw was removed prior to weight bearing
      against those where the screw was left in situ indefinitely. DESIGN:
      Retrospective observational analysis of a consecutive series. SETTING: Acute
      tertiary hospital. PATIENTS: Thirty-three patients with ankle fractures and
      syndesmotic disruption were treated with open reduction, internal fixation, and
      syndesmotic stabilisation with a syndesmotic screw. Three patients defaulted
      follow-up after 1-3 months. In the remaining 30, the syndesmotic screw was
      removed prior to weight bearing in 23 patients and was left in situ in 7
      patients. Mean follow-up was 15 months. METHODS: Assessment with subjective,
      objective, and radiographic criteria was used. Statistical analysis was performed
      with independent groups t-test and chi-square test. RESULTS: There was no
      statistically significant difference between ankle scores, functional outcome or
      range of motion between the two groups. However, there was a significantly higher
      incidence of syndesmotic screw breakage and osteolysis in the group where screws
      were retained. CONCLUSIONS: Judicious fixation of Weber C type injuries with
      syndesmotic screw fixation allows for good functional outcome. Retaining of the
      syndesmotic screw on commencement of weight bearing seems to increase the risk of
      subsequent screw breakage. Removal of the screw prior to weight bearing should be
      performed to avoid such an eventuality.

PMID- 16630622
TI  - Development of analytical procedures to study changes in the composition of meat
      phospholipids caused by induced oxidation.
AB  - Lipid peroxidation affects quality of meat products. The aim of this study was to
      develop a model system and analytical procedures for evaluating the oxidation
      level of meat samples, by studying the changes in meat phospholipids (PL)
      composition and the compounds generated by induced oxidation. Different
      techniques (liquid-, dry column-, accelerated solvent extraction) were
      investigated to identify a suitable lipid extraction system for extracting PL
      from bovine meat and to induce lipid oxidation by using tert-butyl hydroperoxide,
      2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP) or Fe(2+) and Cu(2+) salts.
      Accelerated solvent extraction (ASE) gave results not significantly different
      from the other extraction methods, but offered the advantage of being a rapid and
      solvent-saving procedure. The method using a silica column proved to be valid in
      eluting and separating the components of the phospholipidic fraction and the PL
      standard mixture. The analytical techniques used to analyse oxidation products of
      PL included GC-FID, HPLC with corona charged aerosol detector (CAD), MDA
      determination and the spectrophotometric measurement of peroxide levels (PxL). By
      means of CAD, PL were quantified and their concentration in the lipid extract was
      0.98%+/-0.17 (w/w+/-SD, n=10). The oxidation method induced by ABAP proved to be
      fast and did not produce any artifacts. Three oxidation times were monitored (0,
      90 and 180 min). The oxidation levels after 180 min correlated with a significant
      increase in the peroxide levels PxL (+71%), MDA (+29%) and aldehydes (+75%),
      whereas a decrease or even total disappearance of some unsaturated fatty acids
      was observed. The results obtained demonstrate that the model used in this work
      is useful for studying oxidation of meat phospholipids. Also, the use of the
      innovative detector CAD proved to be a good complementary technique in the
      investigation of lipids.

PMID- 16630623
TI  - Designing polymer matrix for microchip-based double-stranded DNA capillary
      electrophoresis.
AB  - Polyacrylamide (PAM) was used as a model polymer to build up an empirical model
      that relates polymer molecular weight, polymer concentration and solution
      viscosity. The desired random copolymers of acrylamide (AM) and N,N
      dimethylacrylamide (DMA) used as DNA separation media for different
      specifications were synthesized under the guidance of the empirical model. The
      separation performances of rationally designed copolymers were tested in a 1.2 cm
      long separation channel, simulating microchip-based capillary electrophoresis.
      pBR322/HaeIII digest was successfully separated with good separation resolution
      and fast speed. Validation of the sieving ability of our polymers was performed
      in the Agilent 2,100 Bioanalyzer. The results of the 10 bp (base pair) DNA ladder
      separation demonstrate the potential of our approach for the sieving matrix in
      microchip-based electrophoresis.

PMID- 16630624
TI  - New polar-embedded stationary phase for surfactant analysis.
AB  - The separation and identification of surfactants is a challenge due to the
      diversity of surfactants, the complex composition of surfactant raw materials,
      and the complexity of the sample matrices. High-performance liquid chromatography
      (HPLC) is the preferred analytical technique, because it allows the
      characterization of surfactant raw materials according to their composition and
      the quantitation of individual surfactants in complex mixtures. Although many
      HPLC columns are available for surfactant analysis, none of these columns provide
      optimal selectivity for the simultaneous analysis of anionic, non-ionic, and
      cationic surfactants using the same mobile phase system. In this paper, we
      describe a new polar-embedded stationary phase for the simultaneous analysis of
      anionic, non-ionic, and cationic surfactants with a simple and volatile mobile
      phase system containing ammonium acetate buffer and acetonitrile, utilizing
      evaporative light-scattering detection (ELSD). Mobile phase ionic strength and pH
      are important for optimizing chromatographic conditions. The column offers ideal
      selectivity for different types of surfactants, excellent peak shapes, especially
      for cationic surfactants, improved resolution for oligomers in ethoxylated
      surfactants, and compatibility with highly aqueous mobile phases. Thus, it can be
      used not only for quality assurance of individual surfactants, but also for the
      analysis of a variety of surfactant-containing formulations.

PMID- 16630625
TI  - Presence of Marteilia sp. (Paramyxea) in the razor clam Solen marginatus
      (Pennantt, 1777) in Galicia (NW Spain).
AB  - Protistan parasites of the genus Marteilia, phylum Paramyxea, cause the molluscs
      disease named Marteiliosis. Histological observations and transmission electron
      microscopy revealed the presence of life cycle stages of a Marteilia sp. in the
      bivalve mollusc Solen marginatus (Solenidae). Parasites occurred in epithelial
      cells of the digestive ducts and tubules. Early stages (primary cells) presented
      one or several nuclei while advances stages formed a complex of cells-within
      cells (secondary and tertiary cells) culminating in spores. Refringent bodies
      were present inside the presporangia. This is the first report of a Marteilia sp.
      in S. marginatus.

PMID- 16630626
TI  - Detection of viral sequences in semen of honeybees (Apis mellifera): evidence for
      vertical transmission of viruses through drones.
AB  - Honeybees (Apis mellifera) can be attacked by many eukaryotic parasites, and
      bacterial as well as viral pathogens. Especially in combination with the
      ectoparasitic mite Varroa destructor, viral honeybee diseases are becoming a
      major problem in apiculture, causing economic losses worldwide. Several
      horizontal transmission routes are described for some honeybee viruses. Here, we
      report for the first time the detection of viral sequences in semen of honeybee
      drones suggesting mating as another horizontal and/or vertical route of virus
      transmission. Since artificial insemination and controlled mating is widely used
      in honeybee breeding, the impact of our findings for disease transmission is
      discussed.

PMID- 16630627
TI  - Galphaq and its Aktions.

PMID- 16630628
TI  - The type III flagellar export specificity switch is dependent on FliK ruler and a
      molecular clock.
AB  - Salmonella flagellar hook length is controlled at the level of export substrate
      specificity of the FlhB component of the type III flagellar export apparatus.
      FliK is believed to be the hook length sensor and interacts with FlhB to change
      its export specificity upon hook completion. To find properties of FliK expected
      of such a molecular ruler, we assayed binding of FliK to the hook and found that
      the N-terminal domain of FliK (FliK(N)) bound to the hook-capping protein FlgD
      with high affinity and to the hook protein FlgE with low affinity. To investigate
      a possible role of FlgE in hook length control, flgE mutants with partially
      impaired motility were isolated and analyzed. Eight flgE mutants obtained all
      formed flagellar filaments. The mutants produced significantly shorter hooks
      while the hook-type substrates such as FlgE, FliK and FlgD were secreted in large
      amounts, suggesting defective hook assembly with the mutant FlgE proteins. Upon
      overexpression, mutant FlgEs produced hooks of normal length and wild-type FlgE
      produced longer hooks. These results suggest that hook length is dependent on the
      hook polymerization rate and that the start of hook polymerization initiates a
      "time countdown" for the specificity switch to occur or for significant slow down
      of rod/hook-type export after hook length reaches around 55 nm for later
      infrequent FliK(C)-FlhB(C) interaction. We propose that FliK(N) acts as a
      flexible tape measure, but that hook length is also dependent on the hook
      elongation rate and a switch timing mechanism.

PMID- 16630629
TI  - The crystal structure of a plant 3-ketoacyl-CoA thiolase reveals the potential
      for redox control of peroxisomal fatty acid beta-oxidation.
AB  - Crystal structures of peroxisomal Arabidopsis thaliana 3-ketoacyl-CoA thiolase
      (AtKAT), an enzyme of fatty acid beta-oxidation, are reported. The subunit, a
      typical thiolase, is a combination of two similar alpha/beta domains capped with
      a loop domain. The comparison of AtKAT with the Saccharomyces cerevisiae
      homologue (ScKAT) structure reveals a different placement of subunits within the
      functional dimers and that a polypeptide segment forming an extended loop around
      the open catalytic pocket of ScKAT converts to alpha-helix in AtKAT, and occludes
      the active site. A disulfide is formed between Cys192, on this helix, and Cys138,
      a catalytic residue. Access to Cys138 is determined by the structure of this
      polypeptide segment. AtKAT represents an oxidized, previously unknown inactive
      form, whilst ScKAT is the reduced and active enzyme. A high level of sequence
      conservation is observed, including Cys192, in eukaryotic peroxisomal, but not
      mitochondrial or prokaryotic KAT sequences, for this labile loop/helix segment.
      This indicates that KAT activity in peroxisomes is influenced by a
      disulfide/dithiol change linking fatty acid beta-oxidation with redox regulation.

PMID- 16630630
TI  - Modulator of drug activity B from Escherichia coli: crystal structure of a
      prokaryotic homologue of DT-diaphorase.
AB  - Modulator of drug activity B (MdaB) is a putative member of the DT-diaphorase
      family of NAD(P)H:oxidoreductases that afford cellular protection against
      quinonoid compounds. While there have been extensive investigations of mammalian
      homologues, putative prokaryotic members of this enzyme family have received
      little attention. The three-dimensional crystal structure of apo-MdaB reported
      herein exhibits significant structural similarity to a number of flavoproteins,
      including the mammalian DT-diaphorases. We have shown by mass spectrometry that
      the endogenously associated cofactor is flavin adenine dinucleotide and we
      present here the structure of MdaB in complex with this compound. Growth of
      Escherichia coli carrying null mutations in the genes encoding MdaB or quinol
      monooxygenase, the gene for which shares the mdaB promoter, were not affected by
      the presence of menadione. However, over-expression of recombinant quinol
      monooxygenase conferred a state of resistance against both tetracycline and
      adriamycin. This work suggests that the redox cycle formed by these proteins
      protects E. coli from the toxic effects of polyketide compounds rather than the
      oxidative stress of menadione alone.

PMID- 16630631
TI  - The chemotaxis response regulator CheY can catalyze its own acetylation.
AB  - One of the processes by which CheY, the excitatory response regulator of
      chemotaxis in Escherichia coli, can be activated to generate clockwise flagellar
      rotation is by acetyl-CoA synthetase (Acs)-mediated acetylation. Deletion of Acs
      results in defective chemotaxis, indicating the involvement of Acs-mediated
      acetylation in chemotaxis. To investigate whether Acs is the sole acetylating
      agent of CheY, we purified the latter from a delta acs mutant. Mass spectrometry
      analysis revealed that this protein is partially acetylated in spite of the
      absence of Acs, suggesting that CheY can be post-translationally acetylated in
      vivo by additional means. Using [14C]AcCoA in the absence of Acs, we demonstrated
      that one of these means is autoacetylation, with AcCoA serving as an acetyl donor
      and with a rate similar to that of Acs-mediated acetylation. Biochemical
      characterization of autoacetylated CheY and mass spectrometry analysis of its
      tryptic digests revealed that its acetylated lysine residues are those found in
      CheY acetylated by Acs, but the acetylation-level distribution among the
      acetylation sites was different. Like CheY acetylated by Acs, autoacetylated CheY
      could be deacetylated by Acs. Also similarly to the case of Acs-mediated
      acetylation, the phosphodonors of CheY, CheA and acetyl phosphate, each inhibited
      the autoacetylation of CheY, whereas the phosphatase of CheY, CheZ, enhanced it.
      A reduced AcCoA level interfered with chemotaxis to repellents, suggesting that
      CheY autoacetylation may be involved in chemotaxis of E. coli. Interestingly,
      this interference was restricted to repellent addition and was not observed with
      attractant removal, thus endorsing our earlier suggestion that the signaling
      pathway triggered by repellent addition is not identical to that triggered by
      attractant removal.

PMID- 16630632
TI  - Transition-state complex of the purine-specific nucleoside hydrolase of T. vivax:
      enzyme conformational changes and implications for catalysis.
AB  - Nucleoside hydrolases cleave the N-glycosidic bond of ribonucleosides. Crystal
      structures of the purine-specific nucleoside hydrolase from Trypanosoma vivax
      have previously been solved in complex with inhibitors or a substrate. All these
      structures show the dimeric T. vivax nucleoside hydrolase with an "open" active
      site with a highly flexible loop (loop 2) in its vicinity. Here, we present the
      crystal structures of the T. vivax nucleoside hydrolase with both soaked (TvNH
      ImmH(soak)) and co-crystallised (TvNH-ImmH(co)) transition-state inhibitor
      immucillin H (ImmH or (1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D
      ribitol) to 2.1 A and 2.2 A resolution, respectively. In the co-crystallised
      structure, loop 2 is ordered and folds over the active site, establishing
      previously unobserved enzyme-inhibitor interactions. As such this structure
      presents the first complete picture of a purine-specific NH active site,
      including leaving group interactions. In the closed active site, a water channel
      of highly ordered water molecules leads out from the N7 of the nucleoside toward
      bulk solvent, while Trp260 approaches the nucleobase in a tight parallel stacking
      interaction. Together with mutagenesis results, this structure rules out a
      mechanism of leaving group activation by general acid catalysis, as proposed for
      base-aspecific nucleoside hydrolases. Instead, the structure is consistent with
      the previously proposed mechanism of leaving group protonation in the T. vivax
      nucleoside hydrolase where aromatic stacking with Trp260 and an intramolecular
      O5'-H8C hydrogen bond increase the pKa of the N7 sufficiently to allow
      protonation by solvent. A mechanism that couples loop closure to the positioning
      of active site residues is proposed based on a comparison of the soaked structure
      with the co-crystallized structure. Interestingly, the dimer interface area
      increases by 40% upon closure of loop 2, with loop 1 of one subunit interacting
      with loop 2 of the other subunit, suggesting a relationship between the dimeric
      form of the enzyme and its catalytic activity.

PMID- 16630633
TI  - Structural analysis of N-acetylglucosamine-6-phosphate deacetylase apoenzyme from
      Escherichia coli.
AB  - We report the crystal structure of the apoenzyme of N-acetylglucosamine-6
      phosphate (GlcNAc6P) deacetylase from Escherichia coli (EcNAGPase) and the
      spectrometric evidence of the presence of Zn2+ in the native protein. The
      GlcNAc6P deacetylase is an enzyme of the amino sugar catabolic pathway that
      catalyzes the conversion of the GlcNAc6P into glucosamine 6-phosphate (GlcN6P).
      The crystal structure was phased by the single isomorphous replacement with
      anomalous scattering (SIRAS) method using low-resolution (2.9 A) iodine anomalous
      scattering and it was refined against a native dataset up to 2.0 A resolution.
      The structure is similar to two other NAGPases whose structures are known from
      Thermotoga maritima (TmNAGPase) and Bacillus subtilis (BsNAGPase); however, it
      shows a phosphate ion bound at the metal-binding site. Compared to these previous
      structures, the apoenzyme shows extensive conformational changes in two loops
      adjacent to the active site. The E. coli enzyme is a tetramer and its dimer-dimer
      interface was analyzed. The tetrameric structure was confirmed in solution by
      small-angle X-ray scattering data. Although no metal ions were detected in the
      present structure, experiments of photon-induced X-ray emission (PIXE) spectra
      and of inductively coupled plasma emission spectroscopy (ICP-AES) with enzyme
      that was neither exposed to chelating agents nor metal ions during purification,
      revealed the presence of 1.4 atoms of Zn per polypeptide chain. Enzyme
      inactivation by metal-sequestering agents and subsequent reactivation by the
      addition of several divalent cations, demonstrate the role of metal ions in
      EcNAGPase structure and catalysis.

PMID- 16630634
TI  - Mapping a neutralizing epitope on the SARS coronavirus spike protein:
      computational prediction based on affinity-selected peptides.
AB  - Rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens
      like severe acute respiratory syndrome (SARS) coronavirus (CoV) or highly
      pathogenic avian influenza H5N1 virus is of great importance for rational design
      of vaccines against these viruses. Here we combined screening of phage display
      random peptide libraries with a unique computer algorithm "Mapitope" to identify
      the discontinuous epitope of 80R, a potent neutralizing human anti-SARS
      monoclonal antibody against the spike protein. Using two different types of
      random peptide libraries which display cysteine-constrained loops or linear 13-15
      mer peptides, independent panels containing 42 and 18 peptides were isolated,
      respectively. These peptides, which had no apparent homologous motif within or
      between the peptide pools and spike protein, were deconvoluted into amino acid
      pairs (AAPs) by Mapitope and the statistically significant pairs (SSPs) were
      defined. Mapitope analysis of the peptides was first performed on a theoretical
      model of the spike and later on the genuine crystal structure. Three clusters (A,
      B and C) were predicted on both structures with remarkable overlap. Cluster A
      ranked the highest in the algorithm in both models and coincided well with the
      sites of spike protein that are in contact with the receptor, consistent with the
      observation that 80R functions as a potent entry inhibitor. This study
      demonstrates that by using this novel strategy one can rapidly predict and
      identify a neutralizing antibody epitope, even in the absence of the crystal
      structure of its target protein.

PMID- 16630636
TI  - Motor activity rhythms of forced desynchronized rats subjected to restricted
      feeding.
AB  - Although light is the strongest zeitgeber for the circadian pacemaker, other
      stimuli can also produce entrainment. In the rat, periodic restricted feeding
      (RF) is a weak stimulus that may act as a zeitgeber. We tested the effect of RF
      on the motor activity rhythms of rats subjected to forced dissociation. In this
      situation two components, supposed to be related with the ventrolateral and
      dorsomedial areas of the suprachiasmatic nucleus, are detected in their motor
      activity. One component is entrained to the external light-dark cycle (Light
      Dependent Component, LDC) and thus has the same period, while the other has a
      period longer than 24 h (Non-Light Dependent Component, NLDC). This experiment
      examined whether RF can act on one or both of these two rhythms. Rats were
      maintained under the light-dark cycles of 22 h (T22) or 23 h (T23) for 44 days
      with food available for four hours per day. Afterwards the rats received food ad
      libitum, to test the effect of the previous RF condition. Results show that RF
      modifies the manifestation of the two initial rhythms, being this effect stronger
      under T23 than under T22. However RF does not affect the NLDC period. The results
      reveal that the animal can manifest simultaneously several rhythmic patterns.

PMID- 16630635
TI  - Ursolic acid mediates the vasorelaxant activity of Lepechinia caulescens via NO
      release in isolated rat thoracic aorta.
AB  - We have determined that the methanolic extract of L. caulescens (MELc) produced a
      significant vasodilator effect in a concentration-dependent and endothelium
      dependent manner. This relaxation was blocked by N(omega)-nitro-L-arginine
      methylester (L-NAME), indicating that MELc vasodilator properties are endothelium
      mediated due to liberation of nitric oxide (NO). In this paper we aimed to
      corroborate its mode of action. MELc effects on noradrenaline (NA)-induced
      contraction in isolated rat aortic thoracic rings with endothelium (+E), in the
      presence of atropine (0.1 microM) and 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1
      one (ODQ, 1 microM) were conducted. MELc relaxation curve was significantly
      shifted to the right in the presence of ODQ and atropine, thus confirming that
      its mode of action is related with activation of nitric oxide synthase (NOS) and
      the consequent increment in NO formation. Bio-guided study of MELc allowed the
      isolation of ursolic acid (UA, 50 mg) and ursolic-oleanolic acids mixture [UA/OA
      (7:3), 450 mg]. The relaxant effect of UA (0.038-110 microM) was evaluated in
      functional experiments. UA induced a significant relaxation in a concentration-
      and endothelium-dependent manner (IC(50)=44.15 microM) and did not produce a
      vasorelaxant effect on contraction evoked by KCl (80 mM). In addition, NA-induced
      contraction was significantly displaced to the right by UA (30 microM). In order
      to determine its mode of action, UA-induced relaxant effect was evaluated in the
      presence of atropine (0.1 microM), indomethacin (10 microM), L-NAME (100 microM)
      and ODQ (1 microM). Relaxation was blocked by L-NAME and ODQ. On the other hand,
      UA (3 microM) provoked a significant displacement to the left in the relaxation
      curve induced by sodium nitroprusside (SNP, 0.32 nM to 0.1 microM), but it was
      not significant in the presence of Carbamoyl choline (carbachol, 1 nM to 10
      microM). These results indicate that UA-mediated relaxation is endothelium
      dependent, probably due to NO release, and the consequent activation of vascular
      smooth muscle soluble guanylate cyclase (sGC), a signal transduction enzyme that
      forms the second messenger cGMP.

PMID- 16630637
TI  - Intracranial drug-delivery scaffolds: biocompatibility evaluation of sucrose
      acetate isobutyrate gels.
AB  - INTRODUCTION: Sucrose acetate isobutyrate (SAIB) is a water insoluble,
      biodegradable gel used for controlled-release oral and subcutaneous drug
      delivery. We investigated SAIB compatibility in the rat central nervous system
      (CNS) by implanting solutions of SAIB in adult and in neonatal brains. METHODS:
      10-15 microL solutions of SAIB gels in 0-30% ethanol were injected into the
      cerebral cortex of adult Fischer 344 rats. Control animals were implanted with a
      10 mg biodegradable poly anhydride copolymer of poly [bis (p-carboxyphenoxy)
      propane] anhydride and sebacic acid (PCPP:SA). Adult rats were evaluated for
      signs of pain and distress, including changes in posture, facial signs, and
      grooming behavior. 1-2 microL solutions of SAIB gels in 15% ethanol were injected
      into brains of 12-24 h-old rats. Neonatal rats were evaluated for survival. Adult
      and neonatal brains were examined by histopathology 3-48 days after implant.
      RESULTS: Gel implants produced elliptical compression of cortical tissue, cell
      loss, and inflammation. Cell loss appeared to be confined to the implantation
      wound and associated neuronal fields. In adult rats, neurophil compression,
      inflammation, and cell loss appeared similar with the 10-mg PCPP:SA implants and
      the 10-mg SAIB implants. There was no clinical evidence of pain or distress from
      SAIB implants. 1-2 microL implants of SAIB-15% ethanol had no effect on survival
      of neonatal animals. CONCLUSION: Brain implants of SAIB induce a mild to moderate
      inflammatory response and associated neuronal cell damage. The implants appeared
      to be biocompatible in adult and neonatal animals. These results suggest that
      further studies of SAIB as an injectable drug-delivery scaffold for CNS
      therapeutic agents are warranted.

PMID- 16630638
TI  - Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased
      exhalation and target tissue regeneration.
AB  - The aims of the present study were to characterize the subchronic toxicity of
      chloroform by measuring tissue injury, repair, and distribution of chloroform and
      to assess the reasons for the development of tolerance to subchronic chloroform
      toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform
      (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and
      kidney injury were measured by plasma ALT and BUN, respectively, and by
      histopathology. Tissue regeneration was assessed by (3)H-thymidine incorporation
      into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen
      staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at
      selected time points. The levels of chloroform were measured in blood, liver, and
      kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was
      evident after 1 day with all three doses and sustained until 7 days followed by
      complete recovery. Mild to moderate liver injury was observed from 1 to 14 days
      with all three dose levels followed by gradual decrease. Significantly higher
      regenerative response was evident in liver and kidney at 7 days, but the response
      was robust in kidney, preventing progression of injury beyond first week of
      exposure. While the kidney regeneration reached basal levels by 21 days, moderate
      liver regeneration with two higher doses sustained through the end of the dosing
      regimen and 3 days after that. Following repeated exposure for 7, 14, and 30
      days, the blood and tissue levels of chloroform were substantially lower with all
      three dose levels compared to the levels observed with single exposure. Increased
      exhalation of (14)C-chloroform after repeated exposures explains the decreased
      chloroform levels in circulation and tissues. These results suggest that
      toxicokinetics and toxicodynamics (tissue regeneration) contribute to the
      tolerance observed in SW mice to subchronic chloroform toxicity. Neither
      bioactivation nor detoxification appears to play a decisive role in the
      development of this tolerance.

PMID- 16630639
TI  - Rift Valley fever virus noncoding regions of L, M and S segments regulate RNA
      synthesis.
AB  - Rift Valley fever virus (RVFV) (Phlebovirus, Bunyaviridae) possesses a genome
      composed of three negative-stranded RNA molecules. Each segment contains 3' and
      5' noncoding regions with terminal complementary sequences forming a panhandle
      structure. We showed that transcription-replication of the L, M and S segments is
      regulated, and we established a minigenome rescue system expressing a CAT
      reporter to investigate the role of the noncoding regions in this process. The L,
      M and S segment-based minigenomes were shown to drive bona fide transcription and
      replication and to express variable levels of CAT reporter, indicating
      differential promoter activities within the noncoding sequences. In addition, we
      found a good correlation between the relative promoter strength and the abundance
      of viral RNA species in RVFV-infected cells. Altogether, these results show that
      RVFV minigenomes are powerful tools to study transcription and replication and
      constitute a valuable basis to rescue infectious virus from cDNAs.

PMID- 16630640
TI  - Effect of textile wastewaters on Saccharomyces cerevisiae using DNA microarray as
      a tool for genome-wide transcriptomics analysis.
AB  - Textile mill effluents (TMEs) discharged from the textile industry can be
      considered as one class of hypothetical toxicants in the environment. To
      investigate the potential toxicity of TMEs, we applied cDNA microarray technology
      to examine the genome-wide expression profiles in model eukaryote, Saccharomyces
      cerevisiae. The results revealed a rich source of genetic information for the
      yeast cells that were exposed to the untreated and treated TMEs. Among the 5956
      valid genes, 275 genes were up-regulated and 40 genes were down-regulated for the
      untreated TMEs. On the other hand, only 90 genes were up-regulated, and 29 genes
      were down-regulated upon exposure to the treated TMEs. The changes in gene
      expression were also confirmed by RT-PCR. The potent up- and down-regulation of
      genes suggest that yeast cells undergo genome-wide changes in mRNA expression,
      indicative of a stress response. Additionally, a classification into specific
      functional gene categories indicated that untreated and even treated TMEs still
      had toxicity. Especially, the genes related to oxidative stress, such as AHP1,
      ATX1, GRX1, TRX1 and TRX2, were up-regulated in treated TMEs that can directly
      reach to surface and ground waters, and sediments.

PMID- 16630641
TI  - Removal of methanol from pulp and paper mills using combined activated carbon
      adsorption and photocatalytic regeneration.
AB  - Methanol is one of the major hazardous air pollutants emitted from chemical pulp
      mills. Its collection and treatment is required by the Maximum Achievable Control
      Technology portion of the 1998 Cluster Rule. The objective of this study is to
      investigate the technical feasibility of combined adsorption and photocatalytic
      regeneration for the removal and destruction of methanol. To facilitate the
      regeneration, activated carbon (AC) was coated with commercially available
      photocatalyst by a spray desiccation method. Laboratory-scale experiments were
      conducted in a fixed-bed reactor equipped with an 8 W black light UV lamp (peak
      wavelength at 365 nm) at the center. The photocatalyst loaded onto AC had no
      significant impact on the adsorption capacity of the carbon. High humidity was
      found to greatly reduce the material's capacity in the adsorption and
      simultaneous adsorption and photocatalytic oxidation of methanol. The
      photocatalytic regeneration process is limited by the desorption of the
      adsorbate. Increasing desorption rate by using purge air greatly increased the
      regeneration capacity. When the desorption rate was greater than the
      photocatalytic oxidation rate, however, part of the methanol was directly
      desorbed without degradation.

PMID- 16630642
TI  - Effect of systemic herbicides on N2-fixing and phosphate solubilizing
      microorganisms in relation to availability of nitrogen and phosphorus in paddy
      soils of West Bengal.
AB  - A field experiment has been conducted with four systemic herbicides viz.,
      butachlor [N-(butoxymethyl)-2-chloro-2',6'-diethyl-acetanilide], fluchloralin [N
      (2-chloroethyl)-(2,6-dinitro-N-propyl-4-trifluoromethyl) aniline], oxadiazon [5
      terbutyl-3-(2,4-dichloro-5-isopro poxyphenyl)-1,3,4-oxadiazol-2-one] and
      oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenyl)-4-(trifluoromethyl) benzene] at
      their recommended field rates (2.0, 1.5, 0.4 and 0.12kga.i.ha(-1), respectively)
      to investigate their effects on growth and activities of aerobic non-symbiotic
      N(2)-fixing bacteria and phosphate solubilizing microorganisms in relation to
      availability of nitrogen and phosphorus in the rhizosphere soils as well as yield
      of the rice crop (Oryza sativa L cv. IR-36). Application of herbicides, in
      general, highly stimulated the population and activities of the target
      microorganisms, which resulted in a greater amount of atmospheric nitrogen
      fixation and phosphate solubilization in the rhizosphere soils of the test crop.
      The greater microbial activities subsequently augmented the mineralization and
      availability of nitrogen and phosphorus in the soil solution, which in turn
      increased the yield of the crop. Among the herbicides, oxyfluorfen was most
      stimulative followed by fluchloralin and oxadiazon in augmenting the microbial
      activities in soil. Butachlor also accentuated the mineralization and
      availability of nitrogen due to higher incitement of non-symbiotic N(2)-fixing
      bacteria in paddy soil. The grain and straw yields of the crop were also
      significantly increased due to the application of oxyfluorfen (20.2% and 21%)
      followed by fluchloralin (13.1% and 15.4%) and butachlor (9.1% and 10.2%),
      respectively.

PMID- 16630643
TI  - Interactions of sodium azide with triazine herbicides: effect on sorption to
      soils.
AB  - Sodium azide (NaN(3)) is one of the biocides commonly used to inhibit microbial
      growth during sorption experiments. However, a few reports have suggested that
      NaN(3) can react with the analyte of interest. In this study, the interactions of
      NaN(3) with triazine herbicides were investigated and the effect of atrazine
      transformation on its sorption to soil was evaluated. The concentration of
      atrazine in the presence of NaN(3) decreased significantly over period of time.
      After 14 days, only 38% of the initial atrazine concentration (10 mg l(-1)) was
      detected in a solution containing 1,000 mg l(-1) NaN(3) at pH 5.5. The magnitude
      and the rate of atrazine transformation increased with increase in NaN(3) load
      and with decrease in pH. In contrast to atrazine behavior, the concentrations of
      prometon and ametryn did not change during the experiment. GC/MS analysis
      indicated that the chlorine atom of atrazine is replaced by the azide group
      yielding 2-azido-4-(ethylamino)-6-(isopropylamino)-s-triazine. Atrazine
      transformation by NaN(3) significantly affected sorption of herbicide to soil.
      The presence of NaN(3) affects indirectly the sorption of atrazine due to
      competitive effect of its derivative. Our results demonstrated that the
      application of NaN(3) as a biocide in sorption-desorption experiments must be
      carefully evaluated. This issue is vital for sorption experiments conducted over
      long periods of time or/and with concentration of NaN(3) higher than 100 mg l(
      1).

PMID- 16630644
TI  - Kinetics on the decomposition of polychlorinated biphenyls with activated carbon
      supported iron.
AB  - The process of destroying polychlorinated biphenyls (PCBs) generates exhaust
      gases that contain low quantities of PCBs, which cannot be disposed of easily.
      Activated carbon (AC) can be used to adsorb residual PCBs after disposal of high
      level PCBs. We examined the chemical reactivity of AC-supported iron as a
      catalyst to decompose PCB-153, and varied three decomposition parameters
      (temperature, time and iron concentration) under an atmosphere of either air or
      N(2). We measured the Brunauer-Emmett-Teller (BET) surface area and pore volume
      of AC to assess the adsorption capacity of AC before and after decomposition. At
      low temperatures the adsorption process was more important than the decomposition
      process. The decomposition process was completed within 30 and 60 min under air
      and N(2), respectively. The efficiency of PCB-153 decomposition at 350 degrees C
      for 120 min was approximately 100.0% and 97.1% under air and N(2), respectively.
      Analysis of inorganic chloride ions revealed that PCB-153 was effectively
      destroyed during decomposition. The differences between decomposition under air
      and N(2) reflected differences in BET surface and pore volume.

PMID- 16630645
TI  - Plio-Pleistocene climatic change in the Turkana Basin (East Africa): evidence
      from large mammal faunas.
AB  - We investigated palaeoclimatic change in the Turkana Basin during the Pliocene
      climatic shift toward increased aridity in Africa. We analyzed the palaeoecology
      of this area using mammal faunas as environmental indicators. Twenty Plio
      Pleistocene fossil assemblages and a comparative dataset of 16 modern localities
      covering a wide range of climatic and ecological conditions across Africa were
      analyzed. We constructed community profiles using taxonomic variables which
      reflect ecological information. Principal component analysis and bivariate
      correlation were used to study changes in the community structure of these
      mammalian faunas and to draw palaeoenvironmental inferences. Subsequently, least
      squares regressions yielded climatic estimates (annual rainfall and drought
      length) for the studied period. An additional set of 8 modern faunas was used to
      validate these regression models. The climatic estimates showed a drying trend
      throughout the sequence. The biomes in the Turkana Basin changed from semi
      evergreen rain forest to deciduous woodland and savanna during the middle-late
      Pliocene. This was the most important climatic shift detected in our study.
      Evidence suggests a continuous presence of savannas from 2.5 million years ago
      onwards. This pattern of climatic change is consistent with isotopic evidence on
      global climate, and with independently derived regional palaeoenvironmental
      evidence (i.e., micromammals, palaeovegetation, soil carbonates and palaeosols).

PMID- 16630646
TI  - Was Australopithecus anamensis ancestral to A. afarensis? A case of anagenesis in
      the hominin fossil record.
AB  - We tested the hypothesis that early Pliocene Australopithecus anamensis was
      ancestral to A. afarensis by conducting a phylogenetic analysis of four
      temporally successive fossil samples assigned to these species (from earliest to
      latest: Kanapoi, Allia Bay, Laetoli, Hadar) using polarized character-state data
      from 20 morphological characters of the dentition and jaws. If the hypothesis
      that A. anamensis is ancestral to A. afarensis is true, then character-state
      changes between the temporally ordered site-samples should be congruent with
      hypothesized polarity transformations based on outgroup (African great ape)
      conditions. The most parsimonious reconstruction of character-state evolution
      suggests that each of the hominin OTUs shares apomorphies only with geologically
      younger OTUs, as predicted by the hypothesis of ancestry (tree length=31;
      Consistency Index=0.903). This concordance of stratigraphic and character-state
      data supports the idea that the A. anamensis and A. afarensis samples represent
      parts of an anagenetically evolving lineage, or evolutionary species. Each site
      sample appears to capture a different point along this evolutionary trajectory.
      We discuss the implications of this conclusion for the taxonomy and adaptive
      evolution of these early-middle Pliocene hominins.

PMID- 16630647
TI  - Do "savanna" chimpanzees consume C4 resources?
AB  - Several stable carbon isotopic studies have shown that South African
      australopiths consumed significant quantities of C(4) resources (tropical
      grasses, sedges, or animals that eat those foods), but relatively little is known
      about the consumption of such resources by chimpanzees. Here, we present stable
      carbon isotopic data for 36 chimpanzee hair samples from Fongoli, one of the
      driest and most open areas inhabited by chimpanzees. These data suggest that the
      Fongoli chimpanzees consume little in the way of C(4) vegetation or animals that
      eat such vegetation, even though these resources are locally abundant and
      preferred fruits are more widely scattered than at most chimpanzee study sites.
      The homogeneity of the Fongoli results is especially striking and recalls the
      narrow isotopic distribution of stenotopic savanna mammals. This is in stark
      contrast to what has been observed for australopiths, which had highly variable
      diets and consumed about 35% C(4) vegetation on average. Carbon isotope data for
      modern and fossil Papio depict a dietarily variable genus with a tendency to
      consume C(4) vegetation. This trophic flexibility, or willingness to consume C(4)
      savanna resources, may make Papio a more profitable ecological analog for
      australopiths than chimpanzees.

PMID- 16630648
TI  - Changes in blood coagulation of arm and leg veins during a simulated long-haul
      flight.
AB  - INTRODUCTION: Long-haul flights are associated with an increased incidence for
      venous thromboembolic events. At present, markers of coagulation and fibrinolysis
      were only analyzed from arm veins after long distance travel. Respective data
      from leg veins are missing. MATERIALS AND METHODS: Here, we measured these
      parameters in healthy volunteers (n=12) before and after 10 h sitting in modern
      aircraft chairs under normobaric hypoxia (corresponding to 2400 m altitude).
      Blood was collected from arm and leg veins before, immediately after and 1 day
      after sitting in the hypoxic chamber. RESULTS: We did not find any evidence for a
      significant intravasal thrombin and fibrin formation and a changed fibrinolytic
      activity, neither in arm nor in leg vein blood. TAT, PAP, and PAI-1 remained
      unchanged, and the increases of F1+2 in arm veins and of d-dimer in leg veins
      were within the upper reference limits. Moreover, there was no evidence of
      activation of coagulation as measured by thrombelastography (ROTEM(R)) and the
      new Thrombin Dynamic Test at both locations. There was no evidence of arm or leg
      hemoconcentration. CONCLUSIONS: In healthy volunteers, prolonged sitting in
      ergonomically superior aircraft seats does not induce significant changes in
      blood coagulation and fibrinolysis in venous blood of arm or leg. Since this
      study was performed under moderate hypoxia, reduction in oxygen pressure seems
      not to be a crucial factor for venous thrombosis at long-haul flights.

PMID- 16630649
TI  - Amphetamine-induced rapid-onset sensitization: role of novelty, conditioning and
      behavioral parameters.
AB  - BACKGROUND: Environmental factors may modulate sensitization to the locomotor
      activating effects of psychostimulants. In addition, some parameters of locomotor
      activity seem to be more sensitive to detect cocaine-induced behavioral
      sensitization. We examined how novelty and conditioning can modulate a previously
      described rapid-onset type of behavioral sensitization to amphetamine (AMP) in
      mice, using total, peripheral and central open-field locomotion frequencies as
      experimental parameters. METHODS: In the first experiment, mice received an ip
      injection of saline (SAL) or 5.0 mg/kg AMP paired or not with the open-field or
      in their home-cages. Four hours later, all the animals received an ip SAL
      challenge injection and, 15 min later, were observed in the open-field for
      quantification of total, peripheral and central locomotion frequencies. The
      second experiment had a similar protocol, except that mice received a challenge
      injection of 1.5 mg/kg AMP. RESULTS: The priming AMP injection significantly
      increased all the parameters of locomotion of SAL-challenged mice firstly exposed
      to or previously paired (but not unpaired) with the open-field. AMP priming
      injection enhanced total and peripheral locomotion of all AMP-challenged mice but
      only increased central locomotion of mice submitted to novelty or environmental
      conditioning. CONCLUSION: Our results showed: 1) the development of an AMP
      induced rapid-onset sensitization to novelty and rapid-onset environmental
      conditioning in mice, 2) the potentiation of the AMP-induced rapid-onset
      sensitization to an AMP challenge injection by novelty and environmental
      conditioning and 3) the importance of measuring different locomotor activity
      parameters in behavioral sensitization experiments.

PMID- 16630650
TI  - Possible activation of the NO-cyclic GMP-protein kinase G-K+ channels pathway by
      gabapentin on the formalin test.
AB  - The effect of modulators of the nitric oxide-cyclic GMP-protein kinase G-K+
      channels pathway on the local peripheral antinociceptive action induced by
      gabapentin was assessed in the rat 1% formalin test. Local peripheral
      administration of gabapentin produced a dose-dependent antinociception in the
      second phase of the test. Gabapentin-induced antinociception was due to a local
      action as its administration in the contralateral paw was ineffective. Local
      peripheral pretreatment of the paws with NG-L-nitro-arginine methyl ester (L
      NAME, a nitric oxide synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin
      1-one (ODQ, a soluble guanylyl cyclase inhibitor) and KT-5823 (a protein kinase G
      inhibitor) dose-dependently reduced gabapentin-induced antinociception. Likewise,
      glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), 4
      aminopyridine or tetraethylammonium (non-selective inward rectifier K+ channel
      inhibitors) or charybdotoxin (large-conductance Ca2+-activated-K+ channel
      blocker), but not apamin (small-conductance Ca2+-activated-K+ channel blocker) or
      naloxone (opioid receptor antagonist), reduced the antinociception induced by
      gabapentin. Our data suggest that gabapentin could activate the nitric oxide
      cyclic GMP-protein kinase G-K+ channels pathway in order to produce its
      peripheral antinociceptive effect in the rat 1% formalin test.

PMID- 16630651
TI  - Hospitalized smokers: compliance with a nonsmoking policy and its predictors.
AB  - BACKGROUND: Factors associated with compliance with smoke-free policies among
      hospitalized smokers are poorly described. A better understanding of these
      factors may improve smoking cessation during admission and in the long-term.
      METHODS: Two cross-sectional studies were conducted in an urban teaching hospital
      in Spain during 2002 and 2004. We interviewed 229 admitted smokers gathering data
      on smoking history, admission diagnosis, belief that hospitalization is related
      to smoking, policy's awareness, and smoking during admission and place of
      smoking. RESULTS: Among hospitalized patients, approximately a third were current
      smokers. The compliance with the nonsmoking policy in 2002 and 2004 was
      respectively 71.9% (IC95%: 63.9-79.9) and 60.1% (IC95%: 50.9-69.3). In the
      multivariate regression model, factors significantly associated with compliance
      were: contemplation stage, confidence in quitting after discharge, belief that
      current symptoms or illness were related to smoking, and mild withdrawal
      symptoms. CONCLUSIONS: Admission in a smoke-free hospital does not guarantee that
      patients will refrain from smoking. Factors associated with compliance identified
      may be modified by tailored smoking cessation interventions. Our results might
      help physicians to understand inpatients' difficulties to abstain from cigarettes
      and enhance their efforts to take advantage of the hospitalization as a window
      opportunity to quit.

PMID- 16630652
TI  - Comparison of the effect of ovulation-inducing factor (OIF) in the seminal plasma
      of llamas, alpacas, and bulls.
AB  - We have recently reported the presence of an ovulation-inducing factor (OIF) in
      the seminal plasma of llamas and alpacas-species characterized as induced
      ovulators. The study was designed to test the hypothesis that the seminal plasma
      of bulls will induce ovulation in llamas, and to compare the ovulation-inducing
      effect of seminal plasma of conspecific versus hetero-specific males. The seminal
      plasma of alpacas, a closely related induced ovulator (Lama pacos), and cattle, a
      distantly related ruminant species (Bos taurus) considered to be spontaneous
      ovulators, were compared with that of the llama (Lama glama). Ovulation and
      maximum corpus luteum diameter were compared by ultrasonography among female
      llamas (n=19 per group) treated intramuscularly with 2 mL of phosphate buffered
      saline (PBS, negative control) and those treated with 2 mL of seminal plasma of
      bulls, alpacas, or llamas (conspecific control). The diameter of the preovulatory
      follicle did not differ among groups at the time of treatment. Bull seminal
      plasma induced ovulations in 26% (5/19) of llamas compared to 0% (0/19) in PBS
      group (P<0.001). The proportion of females that ovulated was lower (P<0.01) in
      bull seminal plasma group compared to the groups treated with alpaca or llama
      seminal plasma (100%). A corpus luteum was detected on Day 8 (Day 0=treatment) in
      all llamas in which ovulation was detected earlier (Day 2) by ultrasonography.
      The diameter of the CL did not differ among groups. Results document the presence
      of an ovulation-inducing factor in the seminal plasma of B. taurus. The
      interspecies effects of seminal plasma on ovulation and luteal development
      provide rationale for the hypothesis that OIF is conserved among both spontaneous
      and induced ovulating species.

PMID- 16630653
TI  - Ovarian control for assisted reproduction in the domestic cat and wild felids.
AB  - Of the 37 felid species, all but the domestic cat are classified as threatened
      with extinction in all or part of their native range. Additionally, the domestic
      cat is a valuable model for human biomedical research. Propagating some wild
      felids as well as domestic cat populations serving as human models is a major
      challenge primarily due to difficulties in transporting animals between
      facilities to ensure the pairing of genetically matched individuals, behavioral
      incompatibility between pairs and low fertility. Artificial insemination (AI) and
      in vitro fertilization/embryo transfer (IVF/ET) are powerful tools for helping
      manage rare populations. Developing successful assisted reproductive techniques
      requires knowledge of the female reproductive cycle and precise control of
      ovarian activity. Successful ovarian stimulation for AI and IVF/ET has been
      achieved in at least one-third of all cat species. However, sensitivity to a
      given gonadotropin treatment appears highly species-specific, and poor responses
      are common, particularly in felid species that exhibit spontaneous ovulations.
      Furthermore, current gonadotropin regimens have been demonstrated to perturb
      female reproductive function often leading to reduced fertility. Overall, ovarian
      response to exogenous hormonal stimulation has been highly variable, and
      pregnancy success after AI or IVF/ET remains low (<20%) in most species.
      Therefore, there is an immediate need to develop improved regimens that would
      allow more predictable ovarian responses in felids. We contend that recent
      research involving the use of progestins to control the ovary prior to
      gonadotropin stimulation shows promise for providing consistent ovarian
      stimulation in felids.

PMID- 16630654
TI  - High glucose alters proteoglycan expression and the glycosaminoglycan composition
      in placentas of women with gestational diabetes mellitus and in cultured
      trophoblasts.
AB  - Impaired glucose metabolism with diabetes may alter the expressions of
      proteoglycans (PGs), which may impair the biological functions of placenta. In
      this study, we investigated the expression of PGs and their conjugated
      glycosaminoglycan (GAG) composition in the placentas of mothers with gestational
      diabetes mellitus (GDM) and trophoblasts cultured in a high-glucose condition.
      The PGs by guanidine/HCl extraction and DEAE Sepharose fractionation followed by
      GAG degradation enzyme digestion analyses showed that the expression of
      chondroitin sulfate and/or dermatan sulfate (CS/DS) PGs was increased whereas the
      heparan sulfate (HS) PG was decreased in GDM placentas compared to controls.
      Western blot analyses demonstrated that the increased CS/DS PGs in GDM placentas
      were predominantly the small leucine-rich proteoglycans (SLRPs), decorin and
      biglycan. Increased mRNA expression level was consistently shown by quantitative
      real-time PCR. Immunohistochemistry indicated intensive staining of decorin and
      biglycan in the diabetic placenta with different localizations. Additionally, the
      basement membrane HSPG, perlecan was found to contain both CS/DS and HS in GDM
      placentas and plain HS in controls. Similar findings of PG alterations induced by
      hyperglycemia were observed in cultured trophoblast in a high-glucose condition.
      This study demonstrated that hyperglycemia induced not only the gene expressions
      of PGs but also alterations in the carried GAG type and composition.

PMID- 16630655
TI  - Differential expression of placental villous angiopoietin-1 and -2 during early,
      mid and late baboon pregnancy.
AB  - Although vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and
      Ang-2 have important roles in angiogenesis, very little is known about the
      regulation of these factors in the villous placenta during human pregnancy. In
      the present study, to investigate whether placental expression of Ang-1, Ang-2
      and VEGF was altered in a cell-specific manner with advancing baboon gestation,
      the mRNA levels of these growth factors were determined by RT-PCR in cells
      isolated by Percoll gradient centrifugation from and protein localization
      assessed by immunocytochemistry in the villous placenta at early (day 60), mid
      (day 100) and late (day 170, term is 184 days) baboon gestation. Mean (+/-SE) Ang
      1 mRNA levels, relative to 18S rRNA, in villous syncytiotrophoblast (3.92+/-0.68)
      and cytotrophoblast (1.31+/-0.31) cell fractions were highest on day 60 of
      gestation, then decreased by approximately 2.5-fold (P<0.05) to 1.39+/-0.29 and
      0.49+/-0.07, respectively, on day 170. Moreover, Ang-1 mRNA levels in the villous
      stromal cells and Ang-2 mRNA levels in all placental villous cell fractions were
      similar on days 60, 100, and 170 of gestation. In contrast to Ang-1 and Ang-2,
      placental villous cytotrophoblast VEGF mRNA levels were increased 2.94-fold
      (P<0.05) between mid (0.67+/-0.15) and late (1.97+/-0.49) gestation. A
      corresponding decrease in Ang-1, absence of change in Ang-2, and increase in VEGF
      protein immunocytochemical expression were exhibited in placental trophoblast
      with advancing baboon pregnancy. Ang-1/Ang-2 and the angiopoietin Tie-2 receptor
      were expressed in vascular endothelial cells of the villous placenta, indicating
      that these blood vessel cells are a major site of ligand-receptor interaction for
      angiogenesis during primate pregnancy. We conclude that there is a cell-specific
      differential change in placental villous trophoblast expression of VEGF, Ang-1,
      and Ang-2 which we propose is important in regulating angiogenesis in the villous
      placenta during primate pregnancy.

PMID- 16630656
TI  - Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti
      CD52 monoclonal antibodies on chronic lymphocytic leukemia cells.
AB  - Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro,
      showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone.
      We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20
      (rituximab, RIT) or anti-CD52 (campath, CAM) monoclonal antibodies on B-CLL
      cells. Both BOR+RIT and BOR+CAM combinations exerted additive cytotoxicity,
      triggering caspase-dependent apoptosis. The treatment significantly modified
      expression of several apoptosis-regulating proteins, including upregulation of
      Bax or downregulation of Bcl-2 and Mcl-1 by BOR+RIT, as well as downregulation of
      Bcl-2 and XIAP by BOR+CAM. These data suggest the feasibility of concomitant use
      of those agents for the treatment of B-CLL patients.

PMID- 16630657
TI  - Discontinuation of imatinib therapy after achievement of complete molecular
      response in a Ph(+) CML patient treated while in long lasting complete
      cytogenetic remission (CCR) induced by interferon.
AB  - Imatinib has become the gold standard therapy for Ph(+) CML, as it induces
      complete cytogenetic remission (CCR) in 75-90% of patients in chronic phase (CP),
      and up to 40% of these patients obtain at least a 3 log reduction of BCR/ABL
      transcript [Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S,
      et al. Long-term survival benefit and improved complete cytogenetic and molecular
      response rates with imatinib mesylate in Philadelphia chromosome-positive chronic
      phase chronic myeloid leukemia after failure of interferon-alpha. Blood.
      2004;104:1979-1988]. However, it is not yet stated whether continued therapy is
      required to maintain this response or whether imatinib may be discontinued after
      confirmation of a prolonged complete molecular remission (CMR). We here report on
      a Ph(+) CML case in long lasting CCR following interferon-alpha treatment (IFN)
      which reached CMR with imatinib but soon relapsed at molecular level after this
      latter drug discontinuation; we considered the present observation also in the
      light of previously reported data.

PMID- 16630658
TI  - Differences in epidemiology of MDS between Western and Eastern countries: Ethnic
      differences or environmental influence?
AB  - Myelodysplastic syndromes show ethnic differences. Several investigators have
      reported a striking difference in age at diagnosis between Eastern and Western
      MDS patients. Referring to a letter bei Paydas speculating about toxic
      environmental influences as a possible cause for younger age in Asian MDS
      patients, we discuss our experience from a direct comparison of Japanese and
      German MDS, in particular refractory anemia patients.

PMID- 16630659
TI  - HOXA9 gene expression in the chronic myeloid leukemia progression.
AB  - In the present work we study the HOXA9 expression in sequential samples of
      patients with CML using RT-PCR. To obtain a semi-quantitative value, the HOXA9
      expression was referred to the ABL gene in the same sample. The relative HOXA9
      expression was higher in patients in the accelerated phase of the disease
      (p<0.005). Interestingly, a patient with poorer prognosis (high Sokal's score),
      showing the highest HOXA9/ABL ratio, quickly entered a blast crisis and died 5
      months later. These first results could be considered as an evidence of an actual
      biological phenomenon that could provide additional information about the HOXA9
      role in the CML progression.

PMID- 16630660
TI  - CD4 regulation in human lymphoid non-T-cells: a role for the silencer element.
AB  - In humans, the CD4 molecule is expressed on a subset of T-cells and at various
      levels on myeloid and lymphoid cells. The mechanisms regulating human CD4 gene
      expression are yet poorly understood. We speculated that the CD4 silencer, which
      operates in CD8+ T-cells to repress CD4 expression, could be responsible for CD4
      repression in human lymphoid non-T-cells. To test this possibility, we used
      lentiviral vectors carrying CD4 regulatory sequences, with or without the
      silencer element, to express an eGFP reporter gene. We observed that (i) in the
      absence of the silencer element, eGFP expression was detected in CD34+-derived B-
      and NK-cells that otherwise lacked endogenous CD4 mRNA, indicating active
      repression of the CD4 regulatory sequences and (ii) the addition of the CD4
      silencer could repress eGFP expression in these same cells, as well as in human B
      cells generated in vivo in NOD/SCID mice. Collectively, our results suggest that
      beyond its well-characterized function in T-cells, the CD4 silencer also
      regulates CD4 gene expression in human lymphoid non-T-cells.

PMID- 16630661
TI  - Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus
      aureus infection: striking similarities and obvious differences with mammals.
AB  - Zebrafish has emerged as a valuable model for immunological studies. However,
      little is known about the overall picture of its immune response to infectious
      pathogens. Here we present the first systematic study of its immune response to
      Aeromonas salmonicida and Staphylococcus aureus, a Gram-negative and a Gram
      positive bacteria, respectively. Genes induced upon infection were identified
      with suppression subtractive hybridization, with many of them encoding acute
      phase proteins (APPs). When compared with mammals, striking similarities and
      obvious differences have been observed. Both similar APPs (SAA, hepcidin and
      haptoglobin, etc.) and a similar system for the induction of APPs (which involves
      the TLRs, pro-inflammatory cytokines and C/EBPs) were identified, implying
      evolutionary conserved mechanisms among fish and mammals. Some novel APPs were
      also discovered, suggesting different immune strategies adopted by fish species.
      Among which, LECT2 was induced by up to 1000-fold upon infection, shedding new
      lights on the function of this gene. Our results constitute the first
      demonstration of a similar while different immune response in zebrafish and open
      new avenues for the investigation of evolutionary conserved and fish specific
      mechanisms of innate immunity.

PMID- 16630662
TI  - Lack of association between conversation partners' nonverbal behavior predicts
      recurrence of depression, independently of personality.
AB  - High neuroticism and low extraversion are related to depression and its
      recurrence. We investigated whether nonverbal involvement behavior during social
      interaction is one of the factors via which these relations are effectuated. We
      measured nonverbal expressions of involvement from videotaped behavior of
      remitted depressed outpatients (n=101) and their conversation partners, and
      assessed self-reported neuroticism and extraversion scores. During a 2-year
      follow-up, we assessed the recurrence of depression. Twenty-eight participants
      (27.7%) experienced a recurrent episode. Time to recurrence was predicted by
      neuroticism and extraversion, and also by the degree of association between
      levels of nonverbal involvement behavior of conversation partners. The behavioral
      effect did not explain the personality effect. Neuroticism moderated the
      behavioral effect. The results point to the independent relevance of personality
      and nonverbal behavior in the long-term course of depressive disorder.

PMID- 16630663
TI  - Perceived criticism in schizophrenia: a comparison of instruments for the
      assessment of the patient's perspective and its relation to relatives' expressed
      emotion.
AB  - The expression and perception of expressed emotion (EE) in schizophrenic patients
      and their relatives are likely to differ. The presented exploratory study
      compares the two views. EE in relatives of 25 chronic schizophrenic patients was
      assessed using an extended version of the Five-Minute Speech Sample (FMSS).
      Patients rated their relatives with the Perceived Criticism Scale (PCS), the
      Family Emotional Involvement and Criticism Scale (FEICS), and a German
      questionnaire on family atmosphere (FEF). Forty-eight percent of relatives were
      rated high in EE, due to criticism in all cases but one. Patients' assessments of
      the whole family on the FEICS and FEF criticism subscales were related to their
      relatives' EE status. Correlations between the self-rating instruments were
      moderate to good. As the patients' and the relatives' views corresponded with
      regard to the criticism domain, the application of a self-rating instrument may
      be a simple and useful tool for clinical and research purposes.

PMID- 16630664
TI  - Synthesis and antiviral evaluation of alkoxyalkyl esters of acyclic purine and
      pyrimidine nucleoside phosphonates against HIV-1 in vitro.
AB  - Alkoxyalkyl esters of cidofovir, an acyclic nucleoside phosphonate, have been
      shown to have antiviral activities several orders of magnitude greater than
      unmodified cidofovir against cytomegalovirus, herpes simplex virus, vaccinia,
      cowpox, ectromelia and adenoviruses in vitro. Hexadecyloxypropyl-cidofovir is
      orally bioavailable and active in lethal animal models of vaccinia, cowpox,
      ectromelia and cytomegalovirus. To see if this strategy is also applicable to
      other acyclic nucleoside phosphonates, we have converted several
      phosophonomethoxyethyl purines and pyrimidines to their hexadecyloxypropyl,
      octadecyloxyethyl and oleyloxyethyl esters and compared their activity against
      HIV-1 with the activity of the respective unmodified acyclic nucleoside
      phosphonates. The hexadecyloxypropyl esters of phosphonomethoxyethyl-adenine,
      phosphonomethoxyethyl-2,6-diaminopurine and phosphonomethoxyethyl-N(6)
      cyclopropyl-diaminopurine were 3-5 orders of magnitude more active against HIV-1
      in vitro than the parent nucleotides. The EC(50) values for these compounds were
      in the 10-20 pM range with selective indexes of 1,250 to >4,000. The acyclic
      pyrimidine phosphonates were generally inactive against HIV-1 in vitro.
      Phosphonomethoxyethyl-cytosine and phosphonomethoxyethyl-5-fluorocytosine were
      inactive against HIV-1. Surprisingly, hexadecyloxypropyl-phosphonomethoxyethyl-5
      fluorocytosine was active against HIV-1 with a submicromolar EC(50) and a
      selective index of 174. Esterification of acyclic nucleoside phosphonates with
      alkoxyalkyl moieties may represent a general approach for increasing antiviral
      activity and selectivity of this class of antivirals.

PMID- 16630665
TI  - The chronic effects of dietary lead in freshwater juvenile rainbow trout
      (Oncorhynchus mykiss) fed elevated calcium diets.
AB  - This study examined the impact of elevated dietary Ca(2+) on the responses to
      chronic dietary Pb exposure in juvenile rainbow trout. Trout were fed reference
      (0.3microgPb/g, approximately 20mgCa(2+)/g) and Pb-enriched diets ( approximately
      50 or 500microgPb/g) in the presence of background Ca(2+) ( approximately
      20mgCa(2+)/g) or ( approximately 60mgCa(2+)/g) of added Ca(2+) (as CaCO(3)) for
      42 days. The quantitative order of Pb accumulation in tissues reflected the
      exposure pathway of Pb via the diet (per tissue wet weight):
      gut>bone>kidney>liver>spleen>gill>carcass>brain>white muscle. The anterior
      intestine accumulated the most Pb per tissue wet weight, while the bone
      accumulated the most Pb per fish weight. Pb concentrations were much higher in
      the posterior kidney than the anterior kidney. Simultaneous addition of Ca(2+) to
      the diet had an overall protective effect in all the tissues analysed in reducing
      Pb accumulation. The RBCs accumulated 100 times more Pb when compared to the
      plasma, while the whole blood delta-aminolevulinic acid dehydratase was inhibited
      in the high treatment group without added Ca(2+), by the end of the exposure.
      Neither plasma Cl(-), K(+), Mg(2+) nor Na(+), K(+)-ATPase activities in the
      gills, mid- and posterior intestine were affected. However, there were mild
      disruptions in plasma Na(+) and Ca(2+) levels in the elevated Pb and Ca(2+)
      treatment groups, and a significant up-regulation in Na(+), K(+)-ATPase activity
      at the anterior intestine in fish fed the high Pb diets with background or added
      Ca(2+). By day 42, Pb levels in most tissues had either stabilized or started to
      decrease, indicating some capacity for regulation of accumulated loads. We
      conclude that elevated dietary Ca(2+) levels will be protective in reducing Pb
      burdens in freshwater juvenile rainbow trout exposed to environments contaminated
      with waterborne Pb.

PMID- 16630666
TI  - Systematic search for the rate constants that control the exocytotic process from
      chromaffin cells by a genetic algorithm.
AB  - We have recently created a kinetic model that reproduces the dynamics of
      exocytosis with high accuracy. The reconstruction necessitated a search, in a
      multi-dimensional parameter space, for 37 parameters that described the system,
      with no assurance that the parameters, which reconstructed the observations, are
      a unique set. In the present study, a Genetic Algorithm (GA) was used for a
      thorough search in the unknown parameter space, using a strategy of gradual
      increase of the complexity of the analyzed input data. Upon systematic
      incorporation of one to four measurable parameters, used as input signals for the
      analysis, the constraint set on the GA search imposed the convergence of the free
      parameters into a single narrow range. The mean values for each adjustable
      parameter represent a minimum for the fitness function in the multi-dimensional
      parameter space. The GA search demonstrates that the parameters that control the
      kinetics of exocytosis are the rate constants of the steps downstream to
      synaptotagmin binding, and that the equilibrium constant of the binding of
      calcium to Munc13 controls the calcium-dependent priming process. Thus, the
      systematic use of the GA creates a link between specific reactions in the process
      of exocytosis and experimental phenotypes.

PMID- 16630667
TI  - Glanzmann thrombasthenia with endomyocardial fibrosis: a thrombotic paradox.
AB  - We report a paradoxical occurrence of left ventricular thrombus due to
      endomyocardial fibrosis in a six years male child diagnosed as Glanzmann
      thrombasthenia. Such an association has not been reported in literature.

PMID- 16630668
TI  - Hijacking of the host-cell response and translational control during influenza
      virus infection.
AB  - Influenza virus is a major public health problem with annual deaths in the US of
      36,000 with pandemic outbreaks, such as in 1918, resulting in deaths exceeding 20
      million worldwide. Recently, there is much concern over the introduction of
      highly pathogenic avian influenza H5N1 viruses into the human population.
      Influenza virus has evolved complex translational control strategies that utilize
      cap-dependent translation initiation mechanisms and involve the recruitment of
      both viral and host-cell proteins to preferentially synthesize viral proteins and
      prevent activation of antiviral responses. Influenza virus is a member of the
      Orthomyxoviridae family of negative-stranded, segmented RNA viruses and
      represents a particularly attractive model system as viral replication strategies
      are closely intertwined with normal cellular processes including the host defense
      and stress pathways. In this chapter, we review the parallels between
      translational control in influenza virus infected cells and in stressed cells
      with a focus on selective translation of viral mRNAs and the antagonism of the
      dsRNA and host antiviral responses. Moreover, we will discuss how the use of
      genomic technologies such as DNA microarrays and high through-put proteomics can
      be used to gain new insights into the control of protein synthesis during viral
      infection and provide a near comprehensive view of virus-host interactions.

PMID- 16630669
TI  - [Validity and reliability of Spinal Mouse to assess lumbar flexion].
AB  - OBJECTIVES: To evaluate the validity and reliability of the Spinal Mouse model to
      assess lumbar spine flexion. MATERIAL AND METHODS: For the validity study,
      patients with low-back pain underwent radiography to produce 2 lateral
      radiographs, first from the neutral position, and then with full trunk flexion.
      The correlation between mobility as assessed by radiography and the Spinal Mouse
      were evaluated by use of Spearman's correlation coefficient (SCC) for segmental
      mobility (L1-L2, L2-L3, L3-L4, L4-L5 and L5-S1) and global mobility (L1-L5 and L1
      S1). Reliability was studied in healthy volunteers by the intraclass correlation
      coefficient (ICC). RESULTS: A total of 20 patients (8 women) aged 41.6+/-8.6
      (range 24-63), were included in the validity study. The SCC between radiography
      and Spinal Mouse measures were 0.55; 0.64; 0.69; 0.54; 0.19; 0.7; and 0.86 for
      flexion mobility of the L1-L2, L2-L3, L3-L4, L4-L5, L5-S1, L1-L5 and L1-S1,
      respectively. A total of 45 subjects aged 24.2+/-3.7 (range 20-29) were included
      for the reliability study. For intrarater reliability, the ICC was 0.84; 0.89;
      0.96; 0.97; 0.63; 0.95 and 0.83 for the L1-L2, L2-L3, L3-L4, L4-L5, L5-S1, L5-S1,
      L1-L5 and L1-S1, respectively. For interrater reliability, the ICC was 0.75;
      0.81; 0.79; 0.60; 0.83; 0.85, respectively. CONCLUSION: The Spinal Mouse has
      acceptable metrological properties to assess segmental and global lumbar mobility
      during trunk flexion. Its metrological properties are not acceptable to assess
      mobility of L5-S1.

PMID- 16630670
TI  - A randomized phase II trial evaluating standard (50 mg/min) versus low (10
      mg/min) infusion duration of gemcitabine as first-line treatment in advanced non
      small-cell lung cancer patients who are not eligible for platinum-based
      chemotherapy.
AB  - PURPOSE: Gemcitabine is one of the most active drugs against non-small-cell lung
      cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be
      improved by increasing the dose or by increasing the infusion duration. This
      study has been designed in order to explore two different approaches of
      gemcitabine dose intensification in patients with advanced NSCLC. PATIENTS AND
      METHODS: A total of 121 chemonaive patients with locally advanced or metastatic
      NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to
      chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by
      standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150
      min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm
      B). RESULTS: One hundred and seventeen patients were fully analyzed. No
      difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease
      progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in
      both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms
      A and B, respectively. No treatment-related deaths occurred. Main hematological
      toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A
      and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile
      neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4
      thrombocytopenia was more frequently observed in arm B patients (9.9% versus
      1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and
      consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in
      arm A and 41.0% in arm B. CONCLUSION: Intensification of standard doses or
      prolonged infusion schedule did not result in efficacy improvement. Gemcitabine
      infusion duration does not warrant further investigation in patients with
      advanced NSCLC.

PMID- 16630671
TI  - Assessment of representational difference analysis (RDA) to construct informative
      cDNA microarrays for gene expression analysis of species with limited
      transcriptome information, using red and green tomatoes as a model.
AB  - Microarray technology makes it feasible to analyse the expression of thousands of
      different gene elements in a single experiment. Most informative are 'whole
      genome' arrays, where all gene expression products of a single species or variety
      are represented. Such arrays are now available for a limited number of model
      species. However, for other, less well-documented species other routes are still
      necessary to obtain informative arrays. This includes the use of cDNA libraries.
      To enhance the amount of information that can be obtained from cDNA libraries,
      redundancy needs to be minimised, and the number of cDNAs relevant for the
      conditions of interest needs to be increased. Here, we used representational
      difference analysis (RDA), a mRNA subtraction procedure, as a tool to enhance the
      efficiency of cDNA libraries to be used to generate microarrays. Tomato was
      chosen as a model system for a less well-documented species. cDNA libraries for
      two distinct physiological conditions of tomato fruits, red and green, were made.
      The libraries were characterized by sequencing and hybridisation analysis. The
      RDA procedure was shown to be effective in selecting for genes of relevance for
      the physiological conditions under investigation, and against constitutively
      expressed genes. At the same time, redundancy was reduced, but complete
      normalisation was not obtained, and subsequent sequence analysis will be required
      to obtain non-redundant arrays. Further, known and putative ripening-related
      cDNAs were identified in hybridisation experiments on the basis of RNA
      populations as isolated from the green and red stage of ripening.

PMID- 16630672
TI  - The experiences of lecturer practitioners in clinical practice.
AB  - AIM: The aim of the study was to describe and understand the lived experiences of
      teaching for lecturer practitioners in the clinical workplace. BACKGROUND:
      Lecturer practitioners appear to have been introduced into practice to bridge the
      gap between academic and clinical learning although there appears to be little
      empirical evidence of how they work in clinical practice. METHODS: A qualitative
      approach was used in interpreting the transcribed interviews of five lecturer
      practitioners from different practice backgrounds working from the same
      university in the south of England. FINDING: Two synthesised interpretations of
      the lecturer practitioner experiences of teaching were described. One was of
      looking and seeing practice differently and challenging practitioners to do the
      same. The second was of working in the middle of the practice theory gap rather
      than trying to reduce it. CONCLUSIONS: Although the findings are not
      generalisable to other lecturer practitioners the participants appeared to work
      in partnership with practitioners to bring a change in the clinical environment
      where learning was supported and encouraged. The partnership appeared to place
      the onus on the practitioner to develop their practice and the lecturer
      practitioners appeared to work as an educational enabler.

PMID- 16630673
TI  - Using bicistronic IL-4 reporter mice to identify IL-4 expressing cells following
      immunisation with aluminium adjuvant.
AB  - The Th2 dominated immune response induced by aluminium adjuvants remains a major
      limitation to their application to modern vaccines. Previous studies have shown
      that while these adjuvants can initiate Th2 responses in mice with disrupted IL-4
      production or IL-4 signalling, a strong Th1 response becomes evident in these
      situations, suggesting that the main function of IL-4 in the response to
      aluminium adsorbed antigens is to antagonise Th1 induction. In this study we have
      employed the recently described, 4get reporter mice, that express GFP as part of
      a bicistronic IL-4-IRES-GFP mRNA, to identify IL-4 expressing cells in situ
      during an aluminium adjuvant-induced Th2 responses. These preliminary studies
      implicate conventional CD4+ T cells as the sole potential producers of IL-4
      following immunisation with antigen prepared in aluminium adjuvants. Furthermore,
      as GFP positive cells are first detected in the lymph node, our studies indicate
      that these cells may act to block induction of Th1 responses by aluminium
      adjuvants. We conclude that devising strategies to block the effects of IL-4
      production by these cells will facilitate the rational design of vaccine
      adjuvants that induce Th1 responses.

PMID- 16630674
TI  - (137)Cs and (90)Sr uptake by sunflower cultivated under hydroponic conditions.
AB  - The (90)Sr and (137)Cs uptake by the plant Helianthus annuus L. was studied
      during cultivation in a hydroponic medium. The accumulation of radioactivity in
      plants was measured after 2, 4, 8, 16 and 32 days of cultivation. About 12% of
      (137)Cs and 20% of (90)Sr accumulated during the experiments. We did not find any
      differences between the uptake of radioactive and stable caesium and strontium
      isotopes. Radioactivity distribution within the plant was determined by
      autoradiography. (137)Cs was present mainly in nodal segments, leaf veins and
      young leaves. High activity of (90)Sr was localized in leaf veins, stem, central
      root and stomata. The influence of stable elements or analogues on the transfer
      behaviour was investigated. The percentage of non-active caesium and strontium
      concentration in plants decreased with the increasing initial concentration of Cs
      or Sr in the medium. The percentage of (90)Sr activity in plants decreased with
      increasing initial activity of the nuclide in the medium, but the activity of
      (137)Cs in plants increased. The influence of K(+) and NH(4)(+) on the uptake of
      (137)Cs and the influence of Ca(2+) on the uptake of (90)Sr was tested. The
      highest accumulation of (137)Cs (24-27% of the initial activity of (137)Cs) was
      found in the presence of 10 mM potassium and 12 mM ammonium ions. Accumulation of
      about 22% of initial activity of (90)Sr was determined in plants grown on the
      medium with 8 mM calcium ions.

PMID- 16630675
TI  - Radiocarbon dating of archaeological samples (sambaqui) using CO(2) absorption
      and liquid scintillation spectrometry of low background radiation.
AB  - Sambaqui means, in the Tupi language, a hill of shells. The sambaquis are
      archaeological sites with remains of pre-historical Brazilian occupation. Since
      the sambaqui sites in the Rio de Janeiro state region are older than 10,000
      years, the applicability of CO(2) absorption on Carbo-sorb and (14)C
      determination by counting on a low background liquid scintillation counter was
      tested. In the present work, sambaqui shells were treated with H(3)PO(4) in a
      closed vessel in order to generate CO(2). The produced CO(2) was absorbed on
      Carbo-sorb. On saturation about 0.6g of carbon, as CO(2), was mixed with
      commercial liquid scintillation cocktail (Permafluor), and the (14)C activity
      determined by counting on a low background counter, Packard Tricarb 3170 TR/SL,
      for a period of 1000 mins to enable detection of a radiocarbon age of 22,400 BP.
      But only samples with ages up to 3500 BP were submitted to the method because the
      samples had been collected in the municipality of Guapimirim, in archaeological
      sambaqui-type sites belonging to this age range. The same samples were sent to
      the (14)C Laboratory of the Centro de Energia Nuclear na Agricultura (CENA/USP)
      where similar results were obtained.

PMID- 16630676
TI  - Where techno-science meets poverty: medical research and the economy of blood in
      The Gambia, West Africa.
AB  - This paper considers how internationally supported medical research is understood
      and interpreted by its actual and potential study subjects, exposing the limits
      to bioethical discourses amidst economic inequalities and contrasting socio
      cultural worlds. It focuses on the Medical Research Council (MRC) Laboratories in
      The Gambia and particularly their Pneumococcal Vaccine Trial (PVT) that was
      conducted jointly with the Gambian government during 2001-2004. In many respects
      this was an exemplar of international best practice in trial communication and
      informed consent procedures. Yet ethnographic and survey research finds that
      Gambian parents' perspectives on participation are shaped not by trial
      specificities, but by broader, historically shaped views and experiences of the
      MRC as an institution. There is a pervasive view that the MRC offers good, free
      medication to participants, but that it also 'steals blood'. Widespread concerns
      with blood-stealing emerge from local frames of understanding in which blood is
      treated as a tradeable good, in which blood accumulation and depletion in bodily
      processes relates to its exchange in hospital and medical research practices, and
      in which transactions can be more or less (un)reasonable. Yet such thinking,
      rooted in an 'economy of blood', has been overlooked by medical research staff
      and indeed by historians and anthropologists of Africa whose analyses of blood
      stealing have been overly transfixed on rumour and the occult. This paper argues
      that such cultural framings, which guide local critical commentary on trans
      national research orders, require serious attention and need to inform open
      dialogues between scientists and the public if medical research in resource-poor
      settings is to continue to be sustainable and politically legitimate.

PMID- 16630677
TI  - Worsening of obsessive-compulsive symptoms under methadone tapering.
AB  - There is data supporting the hypothesis that the endogenous opioid system may
      play a role in the pathophysiology of Obsessive Compulsive Disorder (OCD). The
      authors report a case of worsening of OCD during methadone tapering, which seems
      to confirm the role of the opioid system in the pathophysiology of OCD. The
      possible involvement of the cortico-limbic-basal-ganglia-thalamic circuit in the
      observed phenomenon is discussed.

PMID- 16630679
TI  - [Phosphatidylcholine lipolysis-lipodissolve: myth or reality?].
AB  - The use of phosphatidylcholine through superficial injections in the aim to
      destroy adipocytes has recently become in great favour in Europe. This appealing
      idea nevertheless needs to be more argued. After one year of use the author
      advocates the fact that lipodissolution will not replace any traditional
      liposuccion, but may be helpful in the unfavourable indications of that
      procedure, thanks to the inflammatory reaction following adipolysis.

PMID- 16630680
TI  - [Role of lipo-filling in the treatment of sequelae in craniosynostosis surgery].
AB  - AIM: This study presents an innovative technique of correction of cranioplasty
      sequelae by lipo-filling in 9 patients treated for cranioplasty in childhood with
      a long-term follow-up. PATIENTS AND METHODS: A prospective study was conducted
      from January 2001 to February 2005, including all patients treated with lipo
      filling technique in the Plastic Surgery department of Lille. For a period of 4
      years and 5 months, 144 patients were operated on with 206 lipo-filling
      procedures: 30 patients for cosmetic purposes and 114 patients for reconstructive
      surgery. In the current investigation, we examined the 9 cases of lipo-filling
      which were performed in complement to craniofacial surgery. All patients
      presented with a sub-cutaneous fronto-temporal deformation which in 3 of the
      cases was associated to a frontal medial defect. The assessment of results was
      performed in the context of post-operative follow-up visits by an observer.
      RESULTS: Nine patients, with a mean age of 16,7 years and a ratio of 1 female for
      2 males underwent a total of 17 lipo-filling procedures. The mean time lapse was
      15,06 months. 9 patients judged the result to be good. No complication was
      observed. CONCLUSION: The S.R. Coleman technique of fat grafting seems to offer
      several advantages, namely the simplicity of the procedure itself, its apparent
      innocuity, its reproducibility, as well as patients and surgeons satisfaction. It
      appears to be an alternative of choice in the corrective surgery of
      craniosynostosis.

PMID- 16630681
TI  - [Effect of information by images on patients' anxiety and comprehension before
      esthetic surgery on the abdominal wall: a prospective randomised trial with 60
      patients].
AB  - Informed consent is a legal and ethical requirement before every surgical
      procedure especially when it comes to esthetic surgery. Obtaining a satisfactory
      understanding of the risks and benefits of the operation by patients remains a
      critical problem. This trial aimed to assess the value of visual information.
      Patients scheduled to undergo abdominoplasty were approached during the first
      preoperative consultation. All patients were given an information leaflet about
      the procedure and completed a Spielberger state trait anxiety inventory (state
      trait inventory, STAI form Y-1): questionnaire to assess baseline anxiety. The
      patients were then randomly assigned to watch or not watch the information CD-Rom
      during the second preoperative consultation. The day before surgery the patient
      completed a second anxiety questionnaire and a knowledge questionnaire. 67
      patients were screened, 2 declined to participate and 5 were unable to complete
      the form. Of the remaining 60 patients 30 were assigned to look at the CD-Rom and
      the remaining 30 not. The groups were similar in regards to age, sex, education
      and initial anxiety score. Patients who watched the CD-Rom were significantly
      less anxious before a esthetic surgery than those who did not (Mean STAI 45 for
      the "image group" [38.2-46.3] vs 55 for the "no image group" [49.9-63.8]).
      Furthermore they also scored higher in the knowledge questionnaire than the "no
      image" group as far as the purpose and the procedural details of the surgery were
      concerned. However statistical difference of knowledge regarding the potential
      complications of the procedure was not found.

PMID- 16630682
TI  - [Anatomic study and clinical application of the skin paddle of the serratus
      anterior free flap].
AB  - SUBJECT: Several authors used musculocutaneous free flaps of serratus anterior.
      However, the localization and dimensions of its skin paddle are not clearly
      defined in the literature. Thus, we realized an anatomical study trying to prove
      the reality of this skin paddle and its localisation, before considering clinical
      applications. PATIENT AND METHODS: Twenty-six dissections on 13 fresh anatomical
      subjects were realized. The protocol consisted in catheterization the thoracic
      branch of the thoracodorsal artery to inject a mixture of iodized product and
      methylene blue. The results were obtained by direct measurement of the blue
      cutaneous area and by radiographic evaluation of the radiopaque area, compared to
      reproducible anatomical reference marks. RESULTS: Twenty-five dissections were
      interpretable with superposable results. The skin paddle was always located
      compared to the 5th, 6th and 7th ribs between the anterior axillary line and the
      mamelonnary line. The area of the skin paddle was 11,75 cm of length (10-14),
      10,75 cm of width (9-12) and 125 cm(2) from surface (110-140). Then, we realized
      between January and December 2003 several clinical applications of this
      anatomical study. We report 12 cases of free flaps of serratus anterior with skin
      paddle for the monitoring of the flap (4 musculocutaneous, 5 osteo-musculo
      cutaneous, 3 of fascia with skin paddle). CONCLUSION: This study comes to the
      support from the anatomical observations from Salmon, the per-operational
      observations of several authors and our own clinical experiment. It certifies the
      autonomy of cutaneous vascularization by branches resulting from the surface
      fascia of the muscle. It specifies the localization and dimensions of the skin
      paddle of the serratus anterior flap in its muscular, osteo-muscular or fascial
      form, which still increases its versatility of use.

PMID- 16630683
TI  - [Bilateral breast reconstruction with the autologous latissimus dorsi flap (a
      retrospective study of 31 consecutive cases)].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to analyse the advantages,
      disadvantages and results of bilateral breast reconstruction by autologous
      latissimus dorsi flap. MATERIAL AND METHOD: Thirty-one two-stage consecutive
      bilateral breast reconstructions were performed by the same operator between 1993
      and 2001. All the reconstructions, in immediate or delayed manner, were indicated
      after radical or skin sparing mastectomy for breast cancer. We used the
      autologous latissimus dorsi flap for all cases. The reconstruction of the second
      breast was always delayed of a few months to avoid back's complications. We
      reviewed the charts of these patients retrospectively. Preoperative data,
      postoperative complications, dorsal seroma occurrence, morphological results and
      patient's satisfaction were evaluated. Median follow-up was 22 months. RESULTS:
      The results confirm the procedure's reliability. Comparative rates of
      postoperative complications are not significantly different between first and
      contralateral breast reconstruction. Functional after-effects of bilateral
      latissimus dorsi harvesting are moderate. The aesthetics results have been judged
      as very good in 84% of cases and good in 16%. The satisfaction rate of the
      patients is high: 90,3% are pleased, 6,5% are satisfied and 3,2% are moderately
      satisfied. CONCLUSION: The autologous latissimus dorsi flap allows a two-stage
      bilateral breast reconstruction. This procedure is not indicated for simultaneous
      bilateral breast reconstruction; it is the main drawback of this technique. So we
      believe that this procedure is an excellent alternative in all the indications of
      sequential bilateral breast reconstructions.

PMID- 16630684
TI  - The influence of montmorillonite clay reinforcement on the performance of a glass
      ionomer restorative.
AB  - OBJECTIVES: A pristine calcium montmorillonite (Ca-MMT) and an organically
      modified 12-amino-dodecanoicacid treated montmorillonite (ADA-MMT) clay were
      evaluated to determine the reinforcement effect on the performance of a glass
      ionomer (GI) restorative ChemFil Superior (Dentsply DeTrey, Kanstanz, Germany) to
      assess the potential as a posterior filling material. METHODS: Mean compressive
      fracture strengths and standard deviations were determined for groups of 30
      cylindrical specimens with 0.5-2.5 wt.% Ca-MMT and ADA-MMT additions to either
      the powder or the liquid elements of the GI. Working characteristics were
      assessed using an oscillating rheometer, the interlayer d-spacings (d(001)) of
      each MMT clay was determined using X-ray diffraction (XRD) and the set cement
      structure was determined by scanning electron microscopy (SEM). RESULTS: The
      addition of up to 1.0 wt.% ADA-MMT resulted in a significant increase in the mean
      compressive fracture strength of the GI utilising the one-way ANOVA and Tukey
      test comparisons at P<0.05. When Ca-MMT clay was added to the GI a significant
      reduction in mean strength was recorded (P<0.05). MMT clay addition to the powder
      and liquid element of the GI in excess of 1.0 wt.% resulted in no significant
      differences in working characteristics although increases in setting times were
      evident for MMT addition up to 1.0 wt.%. XRD patterns identified the d(001) peaks
      for Ca- and ADA-MMT at 2 theta angles of 8.44 degrees and 5.07 degrees and d(001)
      spacings of 1.04 and 1.74 nm, respectively. CONCLUSIONS: The increased interlayer
      d-spacings recorded for ADA-MMT clay demonstrates that the clay had expanded
      layers which may have provided an increased opportunity for the polyacrylic acid
      chains of the GI restorative to diffuse into the MMT galleries. It is postulated
      that the increased interlayer d-spacings for the ADA-MMT clay had a positive
      reinforcing effect on the GI compared with the Ca-MMT clay where no increased
      performance was identified. The study has highlighted the potential for
      increasing the performance of GI restoratives when using an organically modified
      clay as a reinforcement which could increase the potential of GIs as posterior
      filling materials.

PMID- 16630685
TI  - Potential contribution of the forestry sector in Bangladesh to carbon
      sequestration.
AB  - The Kyoto Protocol provides for the involvement of developing countries in an
      atmospheric greenhouse gas reduction regime under its Clean Development Mechanism
      (CDM). Carbon credits are gained from reforestation and afforestation activities
      in developing countries. Bangladesh, a densely populated tropical country in
      South Asia, has a huge degraded forestland which can be reforested by CDM
      projects. To realize the potential of the forestry sector in developing countries
      for full-scale emission mitigation, the carbon sequestration potential of
      different species in different types of plantations should be integrated with the
      carbon trading system under the CDM of the Kyoto Protocol. This paper discusses
      the prospects and problems of carbon trading in Bangladesh, in relation to the
      CDM, in the context of global warming and the potential associated consequences.
      The paper analyzes the effects of reforestation projects on carbon sequestration
      in Bangladesh, in general, and in the hilly Chittagong region, in particular, and
      concludes by demonstrating the carbon trading opportunities. Results showed that
      tree tissue in the forests of Bangladesh stored 92tons of carbon per hectare
      (tC/ha), on average. The results also revealed a gross stock of 190tC/ha in the
      plantations of 13 tree species, ranging in age from 6 to 23 years. The paper
      confirms the huge atmospheric CO(2) offset by the forests if the degraded
      forestlands are reforested by CDM projects, indicating the potential of
      Bangladesh to participate in carbon trading for both its economic and
      environmental benefit. Within the forestry sector itself, some constraints are
      identified; nevertheless, the results of the study can expedite policy decisions
      regarding Bangladesh's participation in carbon trading through the CDM.

PMID- 16630686
TI  - Excellent long-term cancer control with elective nephron-sparing surgery for
      selected renal cell carcinomas measuring more than 4 cm.
AB  - OBJECTIVES: Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC)
      < 4 cm has been accepted as alternative to radical nephrectomy (RN). However, NSS
      for tumours > 4 cm is controversial. We present our experiences and long-term
      oncologic outcome of RCC > 4 cm treated with NSS in a retrospective single
      institutional analysis of 69 patients. METHODS: Between 1975 and 2004, elective
      NSS was performed in 368 patients at our institution, including 69 patients with
      sporadic, nonmetastatic RCC > 4 cm. Overall and cancer-specific survivals were
      estimated using the Kaplan-Meier method. RESULTS: Complications were seen in nine
      patients (13.0%). After a mean follow-up of 6.2 yr (median, 5.8 yr) seven
      patients (10.1%) had died, none of them of tumour-related causes. Tumour
      recurrence was detected in four patients (5.8%). The 5-yr overall survival
      probability was 94.9%. The 10-yr and 15-yr overall survival rates were both
      86.7%. Cancer-specific survival was 100% after 5, 10, and 15 yr. CONCLUSIONS:
      Selected patients with localized RCC even > 4 cm can be treated with elective NSS
      providing optimal long-term outcome. The surgeon's decision for organ-preserving
      surgery should depend on tumour localisation and technical feasibility rather
      than on tumour size.

PMID- 16630687
TI  - More urologic clinical trials in children are needed.

PMID- 16630688
TI  - MRI-guided biopsy of the prostate increases diagnostic performance in men with
      elevated or increasing PSA levels after previous negative TRUS biopsies.
AB  - OBJECTIVES: Repeatedly negative prostate biopsies in individuals with elevated
      prostate specific antigen (PSA) levels can be frustrating for both the patient
      and the urologist. This study was performed to investigate if magnetic resonance
      imaging (MRI)-guided transrectal biopsy increases diagnostic performance in
      individuals with elevated or increasing PSA levels after previous negative
      conventional transrectal ultrasound (TRUS)-guided biopsies. METHODS: 27
      consecutive men with a PSA >4 ng/ml and/or suspicious finding on digital rectal
      examination, suspicious MRI findings, and at least one prior negative prostate
      biopsy were included. Median age was 66 years (mean, 64.5+/-6.8); median PSA was
      10.2 ng/ml (mean, 11.3+/-5.5). MRI-guided biopsy was performed with a closed unit
      at 1.5 Tesla, an MRI-compatible biopsy device, a needle guide, and a titanium
      double-shoot biopsy gun. RESULTS: Median prostate volume was 37.4 cm3 (mean,
      48.4+/-31.5); median volume of tumor suspicious areas on T2w MR images was 0.83
      cm3 (mean, 0.99+/-0.78). The mean number of obtained cores per patient was 5.22+/
      1.45 (median, 5; range, 2-8). Prostate cancer was detected in 55.5% (15 of 27) of
      the men. MRI-guided biopsy could be performed without complications in all cases.
      CONCLUSION: According to our knowledge, this is the largest cohort of consecutive
      men to be examined by MRI-guided transrectal biopsy of the prostate in this
      setting. The method is safe, can be useful to select suspicious areas in the
      prostate, and has the potential to improve cancer detection rate in men with
      previous negative TRUS-biopsies.

PMID- 16630689
TI  - Clinical aspects and surgical treatment of urinary tract endometriosis: our
      experience with 31 cases.
AB  - OBJECTIVES: To present and discuss clinical and surgical management of urologic
      endometriosis. METHODS: Retrospective review of a database on surgical patients
      with endometriosis. RESULTS: Thirty-one patients (incidence, 2.6%; mean age, 33.1
      yr) were affected by urologic endometriosis (bladder, 12; ureter, 15; both, 4).
      Bladder endometriosis was revealed by symptoms related to menses and showed a
      typical endoscopic picture, whereas ureteral involvement had a nonspecific or
      silent symptomatology. All patients affected by bladder endometriosis and
      undergoing transurethral resection (2 cases) developed a bladder recurrence; a
      ureteral recurrence was observed in two of six patients submitted to laparoscopic
      ureterolysis and in one of two patients submitted to ureterectomy with
      ureteroureterostomy. Conversely, no relapses were observed among the 14 patients
      who had partial cystectomy or the 9 who had ureterectomy and
      ureterocystoneostomy. Finally, two patients underwent nephrectomy due to end
      stage renal atrophy. CONCLUSIONS: Cystoscopy is advisable in women with pelvic
      endometriosis with lower urinary tract symptoms; the upper urinary tract should
      be evaluated in all patients with pelvic endometriosis to exclude asymptomatic
      ureteral involvement. Partial cystectomy gives the best results when used to
      treat bladder endometriosis. Ureterolysis can be successful only in case of
      limited ureteral involvement with no urinary obstruction, whereas terminal
      ureterectomy and ureterocystoneostomy should be preferred in case of obstructive
      ureteral endometriosis.

PMID- 16630690
TI  - Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy
      metabolism in the cerebral mitochondria. A comparative study of effects in old
      and young adult rats.
AB  - The content of the neurosteroids, dehydroepiandrosterone (DHEA) in the brain
      decreases with aging. Also the oxidative energy metabolism is known to decrease
      with aging. Hence we examined the effects of treatment with DHEA (0.2 or 1.0
      mg/kg body weight for 7 days) on oxidative energy metabolism in brain
      mitochondria from old and young adult rats. State 3 respiration rates in brain
      mitochondria from old animals were considerably lower than those in young adults.
      Treatment with DHEA stimulated state 3 and state 4 respiration rates in both the
      groups of the animals in a dose-dependent manner. In the old rats following DHEA
      treatment, the state 3 respiration rates became comparable to or increased beyond
      those of untreated young adults. In contrast to the old rats, stimulatory effect
      of DHEA treatment was of greater magnitude in the young adults. However, at
      higher dose (1.0 mg) the effect declined. Cytochrome aa3 content in the brain
      mitochondria from old rats was significantly low but the content of cytochrome b
      was unchanged while the content of cytochromes c+c1 had increased. Treatment with
      DHEA increased the content of cytochrome aa3 and b in old as well as in young
      adult animals. Higher dose of DHEA (1.0 mg) had adverse effect on the content of
      cytochrome c+c1. DHEA treatment stimulated ATPase activity in a dose-dependent
      manner in young adult rats whereas in the old rats the effect on ATPase activity
      was marginal. Dehydrogenases activities were somewhat lower in the old rats. DHEA
      treatment stimulated mitochondrial dehydrogenases activities in both the groups.
      Results of our studies suggest that judicious use of DHEA treatment can improve
      oxidative energy metabolism parameters in brain mitochondria from young adult as
      well as old rats.

PMID- 16630691
TI  - Voluntary control of Necker cube reversals modulates the EEG delta- and gamma
      band response.
AB  - Reversible figures such as the Necker cube make up a well-known class of visual
      phenomena in which an invariant stimulus pattern gives rise to at least two
      different perceptual interpretations. Former EEG studies of our research group
      demonstrated a reversal-related delta response and a frontal enhancement of gamma
      activity during multistable perception which has been interpreted as signaling
      attentional top-down processes. The aim of the present study was to investigate
      the functional involvement of delta and gamma activity in top-down processes more
      explicitly by asking 21 healthy participants to bring the reversal rate under
      voluntary control during viewing of the Necker cube. Slowing down the reversal
      rate should be accomplished by focussing attention to the currently perceived
      alternative while speeding up should be accomplished by shifting attention as
      rapidly as possible from one perspective to the other. EEG was recorded from
      frontal, central, parietal, and occipital locations of both hemispheres. The data
      was analysed on the single-sweep level in the delta and gamma frequency range.
      The results showed that both delta response and gamma power were larger during
      slowing down than speeding up the reversal rate. These findings may indicate that
      more attentional resources have to be allocated by the cognitive system in order
      to prevent a reversal by means of focussed attention than to initiate a reversal
      by attentional shifts.

PMID- 16630692
TI  - Managing low back pain presenting to primary care: where do we go from here?

PMID- 16630693
TI  - Response to "Pain" editorial re: Oaklander et al. (2006).

PMID- 16630694
TI  - Frequency of headache is related to sensitization: a population study.
AB  - Central sensitization is thought to play an important role in the chronification
      of tension-type headache and in the maintenance and exacerbation of the migraine
      attack. It has, however, almost exclusively been studied in highly selected
      patients from headache clinics. The aim of the present study was to evaluate pain
      perception in primary headaches in the general population. Stimulus-response
      functions for pressure versus pain, tenderness and pressure pain thresholds were
      studied in a random sample of 523 adults from the general population. All results
      were controlled for the effects of age and gender. The area under the stimulus
      response function was increased in chronic- and frequent episodic tension-type
      headache compared with subjects without headache (p<0.001, p<0.001) and in
      chronic tension-type headache compared with migraine (p=0.01). Increasing slope
      (p<0.0001) and displacement towards lower pressures was found in the following
      order: no headache, migraine, frequent episodic tension-type headache, chronic
      tension-type headache. The displacement of the stimulus-response function was
      closely associated with frequency of headache. Finally, the stimulus-response
      function tended to be qualitatively altered in patients with frequent headache.
      The findings demonstrate, for the first time in a population-based study, a close
      relation between altered pain perception and chronification of headache, which
      most likely can be explained by central sensitization.

PMID- 16630695
TI  - Mediation of chronic pain: not by neurons alone.

PMID- 16630696
TI  - Severity of mucosal inflammation as a predictor for alterations of visceral
      sensory function in a rat model.
AB  - Transient inflammation is known to alter visceral sensory function and frequently
      precede the onset of symptoms in a subgroup of patients with irritable bowel
      syndrome (IBS). Duration and severity of the initial inflammatory stimulus appear
      to be risk factors for the manifestation of symptoms. Therefore, we aimed to
      characterize dose-dependent effects of trinitrobenzenesulfonic acid
      (TNBS)/ethanol on: (1) colonic mucosa, (2) cytokine release and (3) visceral
      sensory function in a rat model. Acute inflammation was induced in male Lewis
      rats by single administration of various doses of TNBS/ethanol (total of 0.8, 0.4
      or 0.2 ml) in test animals or saline in controls. Assessment of visceromotor
      response (VMR) to colorectal distensions, histological evaluation of severity of
      inflammation, and measurement of pro-inflammatory cytokine levels (IL-2, IL-6)
      using enzyme-linked immunosorbent assay (ELISA) were performed 2h and 3, 14, 28,
      31 and 42 days after induction. Increased serum IL-2 and IL-6 levels were evident
      prior to mucosal lesions 2h after induction of colitis and persist up to 14 days
      (p<0.05 vs. saline), although no histological signs of inflammation were detected
      at 14 days. In the acute phase, VMR was only significantly increased after 0.8 ml
      and 0.4 ml TNBS/ethanol (p<0.05 vs. saline). After 28 days, distension-evoked
      responses were persistently elevated (p<0.05 vs. saline) in 0.8 and 0.4 ml
      TNBS/ethanol-treated rats. In 0.2 ml TNBS/ethanol group, VMR was only enhanced
      after repeated visceral stimulation. Visceral hyperalgesia occurs after a
      transient colitis. However, even a mild acute but asymptomatic colitis can induce
      long-lasting visceral hyperalgesia in the presence of additional stimuli.

PMID- 16630699
TI  - Gene transcription profiling in pollutant exposed mussels (Mytilus spp.) using a
      new low-density oligonucleotide microarray.
AB  - In this study we describe the design and implementation of a novel low-density
      oligonucleotide microarray (the "Mytox-chip"). It consists of 24 mussel genes
      involving both normalizing elements and stress response related genes, each
      represented on the array with one or two different 50 mer oligonucleotide-probe
      reporters spotted in replicated samples on glass-activated slides. Target genes
      were selected on the basis of their potential involvement in mechanisms of
      pollutant and xenobiotic response. They are implicated in both basic and stress
      related cellular processes such as shock response, biotransformation and
      excretion, cell-cycle regulation, immune defense, drug metabolism, etc. The
      microarray was tested on mussels exposed to sublethal concentrations of mercury
      or a crude North Sea oil mixture. RNA samples were extracted from digestive
      glands of control and treated mussels for the synthesis of fluorescence labeled
      cDNAs to be used in dual color hybridizations. Transcription rates of two
      metallothionein iso-genes (mt10 and mt20), a p53-like gene and actin were
      quantitatively estimated also by real-time PCR to confirm microarray data.
      Significant alterations in the gene transcription patterns were seen in response
      to both treatments.

PMID- 16630700
TI  - Association between endometritis diagnosis using a novel intravaginal device and
      reproductive performance in dairy cattle.
AB  - Endometritis reduces reproductive performance in dairy cattle. Diagnosis of
      endometritis is undertaken using a variety of techniques including vaginoscopy,
      manual examination, cytology and ultrasonography. The current studies compared a
      novel test device ("metricheck") that is inserted into the vagina with
      vaginoscopy and then examined the relationship between the metricheck test score
      at 35 days before the start of the seasonal breeding programme and subsequent
      reproductive performance. Cows (n = 191; Study 1) with a history of a peripartum
      disease were examined by both vaginoscopy and the metricheck device and any
      material viewed within the vagina (using vaginoscopy) or retrieved (by the
      metricheck device) was scored on a 0 (no material) to 5 (grossly purulent and
      with an odour) scale. Within each herd the order of examination was randomized
      with sequentially presented pairs of cows. All cows (n = 2793; Study 2) from nine
      herds were examined and scored using the metricheck device 35 days before the
      start of the seasonal breeding programme. All cows were pregnancy tested to
      determine date of conception. In Study 1, more cows were defined as infected
      (i.e. score > 1) following metricheck than vaginoscopic examination (60% versus
      43%, respectively; P < 0.05) and the level of agreement between the two tests was
      moderate (kappa = 0.45). The metricheck device had a higher sensitivity, but
      lower specificity, than vaginoscopy. Endometritis (i.e. score > 1) was detected
      in 21.2% of cows examined in Study 2. The prevalence of endometritis varied among
      herds, declined with time postpartum (P < 0.05) and was higher in cows recorded
      as having a peripartum disease (P < 0.01). Cows diagnosed with endometritis were
      at higher risk of not being detected in oestrus before the start of breeding (P <
      0.01), took longer to be inseminated after the start of the seasonal breeding
      programme (P < 0.01), had a lower first service conception rate (P < 0.01), had
      lower 56-day and final pregnancy rates (P < 0.05) and took longer to conceive
      than cows without endometritis (P < 0.05). It is concluded that examination with
      the metricheck device is more sensitive in detecting endometritis than
      vaginoscopy. Diagnosis of endometritis with the metricheck device was associated
      with poorer subsequent reproductive performance.

PMID- 16630702
TI  - [Pasteurella multocida meningitis following neurosurgery].
AB  - Pasteurella multocida is a rare cause of meningitis. We report a case of P.
      multocida meningitis following a recent neurosurgery procedure and review the 32
      cases previously described.

PMID- 16630703
TI  - The approval process for hyperthermic intraoperative intraperitoneal
      chemotherapy.
AB  - AIMS: To clarify the requirements for Food and Drug Administration approval in
      the United States for hyperthermic intraoperative intraperitoneal chemotherapy
      administration. Also, to review the status of the approval process in Europe.
      METHODS: The obstacles to be overcome for approval by the Food and Drug
      Administration for a new drug approval and for a new device approval were
      reviewed. Drugs approved in the past were examined for their potential for
      current application in this technology. RESULTS: The likelihood that the approval
      of a heater circulator along with the approval for specific chemotherapy agents
      for heated intraoperative intraperitoneal chemotherapy was judged to be remote.
      Rather, the continued use of "homemade heater circulators" and the off-label use
      of appropriate chemotherapy agents augmented by heat will continue to be the
      standard of care. The European community currently has several heater circulators
      approved for hyperthermic intraoperative intraperitoneal chemotherapy
      administration. These devices have been specifically approved for oncologic
      indications. CONCLUSIONS: Continued research and development of heated
      intraoperative intraperitoneal chemotherapy is necessary. As the requirement for
      prevention and treatment of the peritoneal surface component of gastrointestinal
      and gynecologic oncology expands, new investigations into the approval process in
      the United States will be necessary. Publication of results from institutions
      pioneering these new treatment strategies will, of necessity, continue.

PMID- 16630701
TI  - Dorsal cochlear nucleus response properties following acoustic trauma: response
      maps and spontaneous activity.
AB  - Recordings from single neurons in the dorsal cochlear nucleus (DCN) of
      unanesthetized (decerebrate) cats were done to characterize the effects of
      acoustic trauma. Trauma was produced by a 250 Hz band of noise centered at 10
      kHz, presented at 105-120 dB SPL for 4h. After a one-month recovery period,
      neurons were recorded in the DCN. The threshold shift, determined from compound
      action-potential audiograms, showed a sharp threshold elevation of about 60 dB at
      BFs above an edge frequency of 5-10 kHz. The response maps of neurons with best
      frequencies (BFs) above the edge did not show the typical organization of
      excitatory and inhibitory areas seen in the DCN of unexposed animals. Instead,
      neurons showed no response to sound, weak responses that were hard to tune and
      characterize, or "tail" responses, consisting of broadly-tuned, predominantly
      excitatory responses, with a roughly low-pass shape similar to the tuning curves
      of auditory nerve fibers with similar threshold shifts. In some tail responses
      whose BFs were near the edge of the threshold elevation, a second weak high
      frequency response was seen that suggests convergence of auditory nerve inputs
      with widely separated BFs on these cells. Spontaneous rates among neurons with
      elevated thresholds were not increased over those in populations of principal
      neurons in unexposed animals.

PMID- 16630704
TI  - [Amniotic fluid embolism: a review].
AB  - Amniotic fluid embolism occurs rarely but is a leading cause of maternal
      mortality. It is a difficult and somewhat intangible diagnosis that warrants a
      high index of suspicion by physicians. AFE is an unpredictable, unpreventable,
      and, for the most part, an untreatable obstetric emergency. Management of this
      condition includes prompt recognition of the signs and symptoms, aggressive
      resuscitation efforts, and supportive therapy. Any delays in diagnosis and
      treatment can result in increased maternal and/or foetal impairment or death.
      Whereas once the invariable outcome of AFE was death of the mother, today the
      prognosis is somewhat brighter thanks to increased awareness of the syndrome and
      advances in intensive care medicine. No laboratory test is specific to attest the
      diagnosis and autopsy must to be realised in case of maternal death. Although non
      specific, the diagnosis of AFE could be supported by the observation of amniotic
      fluid in the central venous blood as well as in the bronchoalveolar fluid. This
      easy and quick test will be helpful in decision-making. Prompt and aggressive
      supportive treatment is required to lessen an otherwise dismal outcome, which may
      include death and permanent disability. This article provides an account of the
      protean clinical features, pathogenesis, and principles involved in treatment.

PMID- 16630705
TI  - Social anxiety disorder comorbidity in patients with bipolar disorder: a clinical
      replication.
AB  - BACKGROUND: The authors investigated frequency, clinical correlates and onset
      temporal relationship of social anxiety disorder (SAD) in adult patients with a
      diagnosis of bipolar I disorder. METHODS: Subjects were 189 patients whose
      diagnoses were assessed by the Structured Clinical Interview for DSM-III-R
      Patient Version. RESULTS: Twenty-four patients (12.7%) met DSM-III-R criteria for
      lifetime SAD; of these, 19 (10.1% of entire sample) had SAD within the last
      month. Significantly more bipolar patients with comorbid SAD also had substance
      use disorders compared to those without. On the HSCL-90, levels of interpersonal
      sensitivity, obsessiveness, phobic anxiety and paranoid ideation were
      significantly higher in bipolar patients with SAD than in those without. Bipolar
      patients with comorbid SAD recalled separation anxiety problems (school refusal)
      more frequently during childhood than those without. Lifetime SAD comorbidity was
      associated with an earlier age at onset of syndromal bipolar disorder. Pre
      existing OCD tended to delay the onset of bipolarity. CONCLUSIONS: Social anxiety
      disorder comorbidity is not rare among patients with bipolar disorder and is
      likely to affect age of onset and phenomenology of bipolar disorder. These
      findings may influence treatment planning and the possibility of discovering a
      pathophysiological relationship between SAD and bipolarity.

PMID- 16630706
TI  - Effect of fasting on voice in women.
AB  - OBJECTIVE/HYPOTHESIS: To study the effect of fasting on voice in women:
      abstinence from food and water intake between 14 and 18 hours. STUDY DESIGN: A
      prospective study on female subjects. MATERIAL AND METHOD: A total of 28 female
      subjects were included in this study. Their age ranged between 21 and 45 years.
      Subjects with vocal symptoms or vocal fold lesions were excluded. The subjects
      were tested when they were not fasting and while fasting after the first week of
      intermittent fasting during Ramadan. Each subject was first asked about her vocal
      symptoms and the ease of phonation or phonatory effort. Then each underwent
      acoustic analysis and laryngeal video-endostroboscopy. RESULTS: Vocal fatigue was
      the most common reported complaint (53.6%) followed by deepening of the voice
      (21.4%) and harshness (10.2%). Self-reported phonatory effort was significantly
      affected by fasting (P value < 0.001). Out of the 28 subjects, 23 had an increase
      in their phonatory effort. Vocal acoustic parameters did not change markedly
      except for the maximum phonation time, which decreased significantly. Laryngeal
      video-endostroboscopy did not reveal any significant changes during fasting. All
      stroboscopic parameters were the same except for a decrease in the amplitude of
      the mucosal waves in one subject and the presence of a posterior chink in three
      subjects. CONCLUSION: Fasting affects voice. There is an increase in the
      phonatory effort, and vocal fatigue is the most common symptom.

PMID- 16630707
TI  - Testing the Ultra High Risk (prodromal) criteria for the prediction of psychosis
      in a clinical sample of young people.
AB  - Criteria for identifying individuals at imminent risk for onset of a psychotic
      disorder, that is "prodromal" for psychosis, have recently been described. The
      current study set out to test the predictive validity of these criteria in a
      sample of help-seeking young people aged 15-24 years who were referred to, but
      not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status
      was determined at baseline and psychosis status was assessed at 6 month follow
      up. Baseline psychosocial functioning was also assessed as a possible predictor
      of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of
      these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one
      person not meeting UHR criteria developed psychosis in the follow up period.
      Sensitivity, specificity, positive predictive value and negative predictive value
      of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI
      0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994
      (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become
      psychotic than UHR- individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low
      functioning at baseline was associated with psychosis onset in the whole sample
      and in the UHR group. The transition to psychosis rate was much lower than in
      previous samples. This may be a due to the sample being a more general one, not
      identified as possibly "prodromal". Other potential causes of this reduction in
      transition are also explored.

PMID- 16630708
TI  - Factor structure of the Neurological Evaluation Scale in a predominantly African
      American sample of patients with schizophrenia, unaffected relatives, and non
      psychiatric controls.
AB  - OBJECTIVE: This study aimed to identify latent factors of the most widely used
      scale to measure neurological soft signs, the Neurological Evaluation Scale
      (NES), in a sample of schizophrenia patients, their relatives, and non
      psychiatric controls. METHOD: The NES was administered following the format and
      instructions of the original scale [Buchanan, R.W., Heinrichs, D.W., 1989. The
      Neurological Evaluation Scale (NES): a structured instrument for the assessment
      of neurological signs in schizophrenia. Psychiatry Res. 27, 335-350]. Three
      factor analyses were conducted using: (1) 23 items of the scale, (2) these 23
      items in a sample restricted to African American participants, and (3) 12 items
      previously recommended based on adequate inter-rater reliability [Sanders, R.D.,
      Forman, S.D., Pierri, J.N., Baker, R.W., Kelley, M.E., van Kammen, D.P.,
      Keshavan, M.S., 1998. Inter-rater reliability of the neurological examination in
      schizophrenia. Schizophr. Res. 29, 287-292]. RESULTS: Exploratory factor analysis
      in the overall sample (n = 110) revealed three factors of interest: a
      "coordination/Romberg" factor (which included the fist-edge-palm test, finger
      thumb opposition, rapid alternating movements, and the Romberg test), a "sensory
      integration" factor (which included synkinesis, extinction, stereognosis, and
      audio-visual integration), and an "eye movements/tandem walk/overflow movements"
      factor (which included convergence, gaze impersistence, tandem walk, and
      adventitious overflow). Minimal differences were apparent when comparing these
      results with those obtained from an analysis including only African American
      participants (n = 99). Restricting the analysis to only 12 items resulted in two
      factors (with poor discriminant validity and internal consistency), which showed
      few similarities with previously reported exploratory factor analysis results.
      CONCLUSIONS: This study shows that results of empirically-derived factors of the
      NES vary substantially across study samples and research groups, though there
      appear to be at least two consistent latent variables, one related to the
      repetition of motor tasks and another tapping the processing of sensory stimuli.
      The factors demonstrated in the present study are more consistent with the
      original conceptually-derived subscales than prior factor analyses. Thus, until
      further research replicates consistent subscales of subtle neurological
      impairment in a variety of settings and samples, the total NES score may be more
      useful when comparing results across studies. Further research on latent
      neurological factors is needed.

PMID- 16630709
TI  - Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced
      swim and the mouse tail suspension tests.
AB  - Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor
      antagonists exert antidepressant-like effects in a variety of experimental
      paradigms, but their therapeutic application is limited by undesired side
      effects. In contrast, agents that reduce glutamatergic tone by blocking type I
      metabotropic glutamate receptors have been suggested to have more a favorable
      side-effect profile. The present study aimed to compare the effects of mGluR1
      antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy
      cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist
      (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two
      behavioral screening assays commonly used to assess antidepressant-like activity.
      In the modified forced swim test in rats, imipramine (used as a positive control)
      decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented
      (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the
      floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile
      behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP
      increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg).
      In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2
      methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25
      mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was
      biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was
      not affected by treatments. The present study therefore suggests that acute
      blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in
      behavioral despair tests in rats and mice.

PMID- 16630710
TI  - Erythrocyte and plasma protein modification in alcoholism: a possible role of
      acetaldehyde.
AB  - Analysis of the oxidative modification of plasma and erythrocyte ghost proteins
      of chronic alcoholic subjects and healthy non-alcoholics has been performed. It
      was found that increased levels of protein carbonyls in both plasma and
      erythrocyte ghosts from alcoholic subjects occurred in comparison to the levels
      found in preparations from non-alcoholics. Plasma proteins from alcoholic
      subjects did not show evidence of cross-linking, although plasma protein
      concentration and composition were changed. In alcoholic subjects who displayed
      no evidence of abnormal erythrocyte morphology no cross-linking of erythrocyte
      ghost proteins was detectable, whereas the ghosts obtained from alcoholic
      subjects who displayed morphologically abnormal erythrocytes contained cross
      linked proteins. The in vitro treatment with acetaldehyde of erythrocytes from
      non-alcoholics caused increased levels of protein carbonyls and cross-linking
      products in erythrocyte ghost preparations which were similar to those found in
      severe alcoholics. It is concluded that chronic alcohol consumption can cause
      abnormal erythrocyte morphology and increased erythrocyte fragility as a result
      of oxidation and cross-linking of erythrocyte ghost proteins. These effects can
      be ascribed, in part, to exposure of erythrocytes to circulatory acetaldehyde
      which is a product of ethanol metabolism.

PMID- 16630711
TI  - [Family observation of Kawasaki disease: 2 cases in sister and brother].
AB  - This article presents the clinical observation of 2 cases of children suffering
      from Kawasaki disease in the same family at a 7-year interval. This observation
      suggests a genetic predisposition to the disease. Epidemiological surveys
      conducted in Japan for some years point to a genetic factor but without proof.
      Childhood systemic febrile vasculitis is hard to recognise, so its diagnosis is
      often made lately, while there is an effective therapy, which prevents from
      serious cardiovascular complications. Identification of its precise cause, a
      necessary step before any diagnostic laboratory test, will be a major
      breakthrough.

PMID- 16630712
TI  - [Respiratory arrest in the delivery room while lying in the prone position on the
      mothers' chest in 11 full term healthy neonates].

PMID- 16630713
TI  - Updating long-term childhood cancer survival trend with period and mixed
      analysis: good news from population-based estimates in Italy.
AB  - An empirical evaluation of long-term period survival analysis was performed using
      data from the Childhood Cancer Registry of Piedmont, Italy. The aim was to update
      survival time trends and provide 25-year projections for children currently
      diagnosed with cancer. The observed survival experiences up to 15 years after
      diagnosis of five quinquennial cohorts (cohort analysis) were compared to the
      corresponding estimates obtained by period analysis. The two methods generally
      produced very similar findings, although period analysis estimates were slightly
      lower than those obtained from cohort analysis. We then used mixed analysis to
      assess time trends in long-term survival. This showed that the probability of
      surviving 25 years after a cancer in childhood has more than doubled compared to
      cohort analysis estimates from patients diagnosed more than 25 years ago (73% vs.
      32%), providing further evidence of an ongoing improvement in prognosis.

PMID- 16630714
TI  - Adenocarcinoma of the oesophagus and gastric cardia: male preponderance in
      association with obesity.
AB  - Recent evidence links obesity with the rising incidence of oesophageal
      adenocarcinoma. In Ireland between 1995 and 2004 the incidence of oesophageal
      adenocarcinoma increased by 38%, and this coincided with a 67% increase in the
      prevalence of obesity. In this study, a prospective case-control study was
      undertaken in 760 patients presenting to a tertiary centre between 1994 and 2004
      diagnosed with cancer of the oesophagus, gastric cardia or stomach. Data were
      compared with 893 healthy controls. Multivariate logistic regression models were
      used to calculate the odds ratio (OR) of developing either cancer type according
      to quartiles of body mass index (BMI). Based on pre-illness BMI, 82% of patients
      who developed adenocarcinoma of the oesophagus were either overweight or obese
      compared with 59% of the healthy control population (P<0.001). A dose-dependent
      relationship existed between BMI and oesophageal adenocarcinoma in males. The
      adjusted odds ratio was 4.3 (95% CI: 2.3-7.9) among males in the highest BMI
      quartile compared with males in the lowest quartile (P<0.001 for trend). Using
      common cut-off points for BMI, the OR of adenocarcinoma of the lower oesophagus
      was 11.3 times higher (95% CI: 3.5-36.4) for individuals with a BMI >30 kg/m2
      versus individuals with a BMI <22 kg/m2 (P<0.001 for trend). For adenocarcinoma
      of the gastric cardia, males in the top quartile of BMI had an OR of 3.5 (95% CI:
      1.3-9.4) compared with the lowest quartile (P=0.03 for trend). A significant
      (P<0.001) inverse relationship between BMI and oesophageal SCC was observed. The
      odds ratio for adenocarcinoma of the oesophagus, the oesophago-gastric junction
      and gastric cardia rose significantly with increasing BMI. For tumours of the
      lower oesophagus, obesity increased the risk 10.9-fold. The increased risk is
      significant in males only.

PMID- 16630715
TI  - Malignant fibrous histiocytoma of bone: analysis of genomic imbalances by
      comparative genomic hybridisation and C-MYC expression by immunohistochemistry.
AB  - Malignant fibrous histiocytoma (MFH) of bone is a rare, highly malignant tumour.
      As very little is known about its genetic alterations, 26 bone MFHs were analysed
      by comparative genomic hybridisation (CGH). Twenty-three tumours (89%) had DNA
      sequence copy number changes (mean, 7.2 changes per sample). Gains were more
      frequent than losses (gains:losses=2.5:1). Minimal common regions for the most
      frequent gains were 8q21.3-qter (35%), 9q32-qter (35%), 7q22-q31 (35%), 1q21-q23
      (31%), 7p12-pter (31%), 7cen-q11.2 (31%) and 15q21 (31%). Minimal common regions
      for the most frequent losses were 13q21-q22 (42%) and 18q12-q22 (27%). High-level
      amplifications were detected in 8 out of the 26 tumours (31%). The only recurrent
      amplifications, 1q21-q23 and 8q21.2-q22, were present in two samples (8%). As
      copy number increase at 8q24 (the locus of C-MYC) was frequent, the expression of
      C-MYC was studied by immunohistochemistry. Increased levels of c-myc protein were
      detected in 7 out of 21 tumours studied (33%). 81% of the samples studied both by
      CGH and immunohistochemistry showed concordant results. Furthermore, the findings
      of the present study were compared to previous publications on osteosarcoma, soft
      tissue MFH and fibrosarcoma of bone. Clear differences were detected in CGH
      aberration patterns, further supporting the concept of bone MFH as an individual
      bone tumour entity. Finally, the findings of the present study reflect well the
      high malignancy and aggressive nature of bone MFH.

PMID- 16630716
TI  - Mechanisms of self-renewal in human embryonic stem cells.
AB  - Embryonic stem cells (ESCs) are the pluripotent cell population derived from the
      inner cell mass of pre-implantation embryos and are characterised by prolonged
      self-renewal and the potential to differentiate into cells representing all three
      germ layers both in vitro and in vivo. Preservation of the undifferentiated
      status of the ESC population requires the maintenance of self-renewal whilst
      inhibiting differentiation and regulating senescence and apoptosis. In this
      review, we discuss the intrinsic and extrinsic factors associated with self
      renewal process, together with possible signalling pathway interactions and
      mechanisms of regulation.

PMID- 16630717
TI  - A functional polymorphism in the promoter region of leptin gene increases
      susceptibility for non-small cell lung cancer.
AB  - Leptin hormone and receptor have been associated to cancer development and were
      identified in lung tissue. In this study, a functional polymorphism in the 5'
      flanking region of the leptin gene (LEP -2548 G/A) was found to increase
      susceptibility for non-small cell lung cancer [odds ratio (OR), 1.97; 95%
      confidence interval (CI), 1.13-3.43]. Age-adjusted logistic regression analysis
      in men indicated an association of AA genotype with adenocarcinoma (OR, 4.29; CI,
      1.64-11.72) and squamous cell carcinoma (OR, 3.19; CI, 1.26-8.13). Logistic
      regression analysis confirmed the AA genotype as an independent risk factor for
      lung cancer after adjustment for age and gender (OR, 2.57; CI, 1.34-4.92). The AA
      genotype was overrepresented only in patients with non-metastatic disease (OR,
      1.86; CI, 1.13-3.04). Kaplan-Meier analysis demonstrated an earlier age of onset
      for lung cancer in AA carriers (P=0.023). Results suggest the existence of
      genetic susceptibility for lung cancer in carriers of this LEP functional
      polymorphism. Further studies are warranted to extend knowledge of leptin
      involvement in lung cancer.

PMID- 16630718
TI  - Protein tyrosine phosphatases regulate arachidonic acid release, StAR induction
      and steroidogenesis acting on a hormone-dependent arachidonic acid-preferring
      acyl-CoA synthetase.
AB  - The activation of the rate-limiting step in steroid biosynthesis, that is the
      transport of cholesterol into the mitochondria, is dependent on PKA-mediated
      events triggered by hormones like ACTH and LH. Two of such events are the protein
      tyrosine dephosphorylation mediated by protein tyrosine phosphatases (PTPs) and
      the release of arachidonic acid (AA) mediated by two enzymes, ACS4 (acyl-CoA
      synthetase 4) and Acot2 (mitochondrial thioesterase). ACTH and LH regulate the
      activity of PTPs and Acot2 and promote the induction of ACS4. Here we analyzed
      the involvement of PTPs on the expression of ACS4. We found that two PTP
      inhibitors, acting through different mechanisms, are both able to abrogate the
      hormonal effect on ACS4 induction. PTP inhibitors also reduce the effect of cAMP
      on steroidogenesis and on the level of StAR protein, which facilitates the access
      of cholesterol into the mitochondria. Moreover, our results indicate that
      exogenous AA is able to overcome the inhibition produced by PTP inhibitors on
      StAR protein level and steroidogenesis. Then, here we describe a link between PTP
      activity and AA release, since ACS4 induction is under the control of PTP
      activity, being a key event for AA release, StAR induction and steroidogenesis.

PMID- 16630719
TI  - Enzymatic production of biodiesel from cotton seed oil using t-butanol as a
      solvent.
AB  - The enzymatic production of biodiesel by methanolysis of cottonseed oil was
      studied using immobilized Candida antarctica lipase as catalyst in t-butanol
      solvent. Methyl ester production and triacylglycerol disappearance were followed
      by HPLC chromatography. It was found, using a batch system, that enzyme
      inhibition caused by undissolved methanol was eliminated by adding t-butanol to
      the reaction medium, which also gave a noticeable increase of reaction rate and
      ester yield. The effect of t-butanol, methanol concentration and temperature on
      this system was determined. A methanolysis yield of 97% was observed after 24h at
      50 degrees C with a reaction mixture containing 32.5% t-butanol, 13.5% methanol,
      54% oil and 0.017 g enzyme (g oil)(-1). With the same mixture, a 95% ester yield
      was obtained using a one step fixed bed continuous reactor with a flow rate of
      9.6 mlh(-1) (g enzyme)(-1). Experiments with the continuous reactor over 500 h
      did not show any appreciable decrease in ester yields.

PMID- 16630720
TI  - Sulfide removal by moderate oxygenation of anaerobic sludge environments.
AB  - Introduction of a limited amount of oxygen to anaerobic bioreactors is proposed
      as a simple technique to lower the level of sulfide in the biogas. This paper
      presents the results of a bioreactor study and of batch experiments that were
      performed to obtain better insight into the fate of sulfur compounds and oxygen
      during micro-aerobic sulfide oxidation. Introduction of a low airflow (0.7-0.9
      m(3)m(-3)d(-1), corresponding to an O(2)/S molar ratio of 8-10) to a fluidized
      bed reactor fed with low-sulfate vinasse was sufficient to reduce the biogas
      H(2)S-content to an undetectable level. Sulfide was initially oxidized to
      elemental sulfur, thiosulfate and - most probably - polysulfide. Significant
      sulfate production did not occur. Bioreactor sludge sampled from the reactor
      after three weeks' micro-aerobic operation was much faster in oxidizing sulfur
      than bioreactor sludge sampled during fully anaerobic reactor operation. The
      reaction proceeded faster with increasing O(2)/sulfide ratios.

PMID- 16630721
TI  - Development of lipopeptides for inhibiting 20S proteasomes.
AB  - Proteasomes are responsible for the cytoplasmic turnover of the vast majority of
      proteins including regulatory proteins. We have synthesized lipopeptides a new
      class of non-covalent inhibitors of the 20S proteasome and assayed their
      inhibitory capacities. Their ability to inhibit at micromolar concentrations
      chymotrypsin-like and post-acid activities depends on peptide length (3 or 6
      amino acids), sequence (presence of a positively or negatively charged amino
      acid), and alkyl chain length (C6-C18). These structural features could be varied
      to selectively inhibit one or more of the three proteasome activities.

PMID- 16630722
TI  - Enantiomerically pure 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists.
AB  - The 1,4-benzodiazepine-2,5-dione is a suitable template to disrupt the
      interaction between p53 and Hdm2. The development of an enantioselective
      synthesis disclosed the stereochemistry of the active enantiomer. An in vitro p53
      peptide displacement assay identified active compounds. These activities were
      confirmed in several cell-based assays including induction of the p53 regulated
      gene (PIG-3) and caspase activity.

PMID- 16630723
TI  - Design and evaluation of new antipsoriatic antedrug candidates having 16-en-22
      oxa-vitamin D3 structures.
AB  - Design, synthesis, and in vitro and in vivo evaluation of a series of
      antipsoriatic antedrugs having 16-en-22-oxa-vitamin D3 are described. Among the
      seven compounds examined, two are promising: ester 5c and amide 5f, both of which
      exhibit greater potent antiproliferation activity with lessened calcemic activity
      than the presently prescribed maxacalcitol (2).

PMID- 16630724
TI  - Purification and characterization of Mycobacterium tuberculosis 1D-myo-inosityl-2
      acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase, MshB, a mycothiol
      biosynthetic enzyme.
AB  - Mycothiol (MSH, AcCys-GlcN-Ins) is the major low molecular weight thiol in
      actinomycetes and is essential for growth of Mycobacterium tuberculosis. MshB,
      the GlcNAc-Ins deacetylase, is a key enzyme in MSH biosynthesis. MshB from M.
      tuberculosis was cloned, expressed, purified, and its properties characterized.
      Values of k(cat) and K(m) for MshB were determined for the biological substrate,
      GlcNAc-Ins, and several other good substrates. The substrate specificity of MshB
      was compared to that of M. tuberculosis mycothiol S-conjugate amidase (Mca), a
      homologous enzyme having weak GlcNAc-Ins deacetylase activity. Both enzymes are
      metalloamidases with overlapping amidase activity toward mycothiol S-conjugates
      (AcCySR-GlcN-Ins). The Ins residue and hydrophobic R groups enhance the activity
      with both MshB and Mca, but changes in the acyl group attached to GlcN have
      opposite effects on the two enzymes.

PMID- 16630725
TI  - Expression and functional purification of a glycosylation deficient version of
      the human adenosine 2a receptor for structural studies.
AB  - A glycosylation deficient (dG) version of the human adenosine 2a receptor (hA2aR)
      was made in Pichia pastoris strain SMD1163. Under optimal conditions, expression
      levels of between 8 and 12pmol receptor/mg membrane protein were obtained
      routinely. In a shake flask, this is equivalent to ca. 0.2mg of receptor per
      litre of culture. The level of functional receptor produced was essentially
      independent of the pH of the yeast media. In contrast to this, addition of the
      hA2aR antagonist theophylline to the culture media caused a twofold increase in
      receptor expression. A similar effect on dG hA2aR production was also observed
      when the induction temperature was reduced from 29 to 22 degrees C. In P.
      pastoris membranes, dG hA2aR had native-like pharmacological properties, binding
      antagonists with rank potency ZM241385>XAC>theophylline, as well as the agonist
      NECA. Furthermore, the receptor was made with its large (ca. 120 amino acid) C
      terminal domain intact. dG hA2aR was purified to homogeneity in three steps, and
      its identity confirmed by electrospray tandem mass spectrometry following
      digestion with trypsin. The secondary structure of the entire receptor is largely
      (ca. 81%) alpha-helical. Purified dG hA2aR bound [(3)H]ZM241385 in a saturable
      manner with a B(max) of 18.1+/-0.5 nmol/mg protein, close to the theoretical
      B(max) value for pure protein (21.3 nmol/mg protein), showing that the receptor
      had retained its functionality during the purification process. Regular
      production of pure dG hA2aR in milligram quantities has enabled crystallisation
      trials to be started.

PMID- 16630726
TI  - The fate of platinum(II) and platinum(IV) anti-cancer agents in cancer cells and
      tumours.
AB  - SRIXE mapping has been used to gain insight into the fate of platinum(II) and
      platinum(IV) complexes in cells and tumours treated with anticancer active
      complexes to facilitate the development of improved drugs. SRIXE maps were
      collected of thin sections of human ovarian (A2780) cancer cells treated with
      bromine containing platinum complexes, cis-[PtCl(2)(3-Brpyr)(NH(3))] (3-Brpyr=3
      bromopyridine) and cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)]
      (OAcBr=bromoacetate), or a platinum complex with an intercalator attached cis
      [PtCl(2)(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH(3))]. After 24h the
      complexes appear to be localised in the cell nucleus with a lower concentration
      in the surrounding cytoplasm. In cells treated with cis-[PtCl(2)(3-Brpyr)(NH(3))]
      the concentration of bromine was substantially higher than in control cells and
      the bromine was co-localised with the platinum consistent with the 3
      bromopyridine ligand remaining bound to the platinum. The cells treated with
      cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] also showed an increased level of
      bromine, but to a much lesser extent than for those treated with cis-[PtCl(2)(3
      Brpyr)(NH(3))] suggestive of substantial reduction of the platinum(IV) complex.
      Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour
      xenograft removed from a mouse 3h after treatment with cis,trans,cis
      [PtCl(2)(OH)(2)(NH(3))(2)] and revealed selective uptake of platinum by one cell.

PMID- 16630727
TI  - Molecular systematics of basal subfamilies of ants using 28S rRNA (Hymenoptera:
      Formicidae).
AB  - For many years, the ant subfamily Ponerinae was hypothesized to contain the basal
      (early branching) lineages of ants. Recently the Ponerinae were reclassified into
      six poneromorph subfamilies based on morphological analysis. We evaluate this new
      poneromorph classification using 1240 base pairs of DNA sequence data obtained
      from 28S rRNA gene sequences of 68 terminal taxa. The molecular tree supported
      the monophyly of the ant family Formicidae, with 100% parsimony bootstrap (PB)
      support and posterior probabilities (PP) of 1.00, with the ant subfamily
      Leptanillinae as a sister group to all other ants (PB=62, PP=93). However, our
      analyses strongly support the polyphyly of the Poneromorph subfamilies (sensu
      Bolton). The Ectatomminae and Heteroponerinae are more closely related to the
      Formicoid subfamilies than to the rest of the poneromophs (PB=96, PP=100). The
      Amblyoponinae (PB=52, PP=96), Paraponerinae (PB=100, PP=100), Ponerinae (PB<50,
      PP=71), and Proceratiinae (PB=98, PP=100) appear as distinct lineages at the base
      of the tree and are identified as a poneroid grade. Monophyletic origins for the
      poneroid subfamilies Amblyoponinae, Paraponerinae, Ponerinae and Proceratiinae
      are supported in our analysis. However, the genus Platythyrea forms a distinct
      sister group to the Ponerini within the Ponerinae. The Heteroponerinae, based on
      our sample of Heteroponera, are associated with the subfamily Ectatomminae
      (PB=98, PP=100). Furthermore, our data indicate the genus Probolomyrmex belongs
      to the Proceratiinae as suggested by recent morphological analysis (PB=98,
      PP=100).

PMID- 16630728
TI  - Differential expression of connexin 43 in mouse mammary cells.
AB  - In this study we have employed suppressive subtractive hybridization (SSH)
      analysis to investigate differential gene expression in primary mouse mammary
      epithelial cells (PMMEC) cultured under mildly apoptotic/quiescent and
      differentiating conditions. Among a small group of genes whose expression was
      differentially regulated was connexin 43. In vitro, connexin 43 mRNA and protein
      were detectable in PMMEC cultured under proliferative or mildly apoptotic
      conditions. The level of connexin 43 mRNA expression in vivo was also
      investigated. High levels of expression were found to be associated with the
      periods of greatest glandular plasticity (pubertal expansion of the mammary tree,
      early pregnancy and during early involution). Thus, terminally differentiated
      cells in vivo and in vitro did not express connexin 43 mRNA suggesting that
      connexin 43 expression, and perhaps facilitated gap junction communication, is
      associated with undifferentiated progenitor cell populations.

PMID- 16630729
TI  - Stromal cell derived factor-1 acutely promotes neural progenitor cell
      proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal
      pathways.
AB  - Stromal cell derived factor-1 (SDF-1), a member of the chemotactic cytokine
      family, has attracted attention in recent years. It participates in diverse
      processes such as the regulation of neuronal migration and activation of CD4+ T
      cells; it is also a co-receptor for human immunodeficiency virus-1 (HIV-1). Here,
      we show that the proliferation of neural progenitor cells dissociated from rat
      cortex and cultured in vitro with basic fibroblast growth factor (bFGF) is
      stimulated by SDF-1. PD98059 and wortmannin, which are, respectively, specific
      inhibitors of the extracellular regulated kinase1/2 (ERK1/2) and
      phosphatidylinositol-3 kinase (PI-3K) signal pathways, markedly attenuate this
      stimulation of proliferation. These findings indicate that SDF-1 acutely promotes
      the proliferation of NPCs in vitro involving the ERK1/2 and PI-3 kinase pathways,
      suggesting that it plays a basic role in the development of neural progenitors.

PMID- 16630730
TI  - Basolateral amygdala noradrenergic activity mediates corticosterone-induced
      enhancement of auditory fear conditioning.
AB  - The present experiment examined whether posttraining noradrenergic activity
      within the basolateral complex of the amygdala (BLA) is required for mediating
      the facilitating effects of acutely administered glucocorticoids on memory for
      auditory-cue classical fear conditioning. Male Sprague-Dawley rats received five
      pairings of a single-frequency auditory stimulus and footshock, followed
      immediately by bilateral infusions of the beta1-adrenoceptor antagonist atenolol
      (0.5 microg in 0.2 microl) or saline into the BLA together with a subcutaneous
      injection of either corticosterone (3.0 mg/kg) or vehicle. Retention was tested
      24 h later in a novel test chamber and suppression of ongoing motor behavior
      served as the measure of conditioned fear. Corticosterone facilitated memory as
      assessed by suppression of motor activity during the 10-s presentation of the
      auditory stimulus and intra-BLA administration of atenolol selectively blocked
      this corticosterone-induced memory enhancement. These findings provide evidence
      that, as found with other emotionally arousing tasks, the enhancing effects of
      corticosterone on memory consolidation of auditory-cue fear conditioning require
      posttraining noradrenergic activity within the BLA.

PMID- 16630731
TI  - Computed tomography versus magnetic resonance imaging of endoleaks after EVAR.
AB  - AIM: The aim of study was to compare the sensitivity of MRI and CTA for endoleak
      detection and classification after EVAR. PATIENTS & METHODS: Twenty-eight
      patients, between 2 days and 65 months after EVAR, were evaluated with both CT
      and MRI. Twenty-five patients had an Ancure graft and the other three had an
      Excluder. The MRI protocol for endoleak evaluation included: a T1-weighted spin
      echo, a high-resolution 3D CE-MRA, and a post-contrast T1-weighted spin echo. In
      total 40 ml Gadolinium was administered. The CT protocol consisted of a blank
      survey followed by a spiral CT angiography (CTA) using 140 ml of Ultravist. An
      experienced, blinded observer evaluated all CTs and MRIs. RESULTS: Using MRI and
      MRA techniques significantly more endoleaks (23/35) were detected than with CTA
      (11/35) (p=0.01, Chi-Square). CT could not determine the type of endoleak in 3 of
      the 11 endoleaks detected and was uncertain in one. MRI was uncertain about the
      type in 14 of the 23 endoleaks detected. All endoleaks visible on CT were visible
      by MRI as well. CONCLUSIONS: MRI techniques are more sensitive for the detection
      of endoleak after endovascular AAA repair than CT.

PMID- 16630733
TI  - Architecture with GIDEON, a program for design in structural DNA nanotechnology.
AB  - We present geometry based design strategies for DNA nanostructures. The
      strategies have been implemented with GIDEON-a graphical integrated development
      environment for oligonucleotides. GIDEON has a highly flexible graphical user
      interface that facilitates the development of simple yet precise models, and the
      evaluation of strains therein. Models are built on a simple model of undistorted
      B-DNA double-helical domains. Simple point and click manipulations of the model
      allow the minimization of strain in the phosphate-backbone linkages between these
      domains and the identification of any steric clashes that might occur as a
      result. Detailed analysis of 3D triangles yields clear predictions of the strains
      associated with triangles of different sizes. We have carried out experiments
      that confirm that 3D triangles form well only when their geometrical strain is
      less than 4% deviation from the estimated relaxed structure. Thus geometry-based
      techniques alone, without detailed energetic considerations, can be used to
      explain certain general trends in DNA structure formation. We have used GIDEON to
      build detailed models of double crossover and triple crossover molecules,
      evaluating the non-planarity associated with base tilt and junction
      misalignments. Computer modeling using a graphical user interface overcomes the
      limited precision of physical models for larger systems, and the limited
      interaction rate associated with earlier, command-line driven software.

PMID- 16630734
TI  - Rate of metabolism during lactation in small terrestrial mammals (Crocidura
      russula, Mus domesticus and Microtus arvalis).
AB  - Basal rate of metabolism (BMR) and resting maternal rate of metabolism around
      peak lactation (RMR(L)) were measured in Crocidura russula, Mus domesticus and
      Microtus arvalis. These species have a moderate or high BMR relative to the
      scaling relationship of Kleiber. One goal of the study was to check whether
      females of these species show elevated rates of metabolism during lactation. A
      second goal was to test for a possible intraspecific correlation between the
      level of BMR and the change in rate of metabolism associated with lactation.
      RMR(L) was significantly higher than BMR in all species when changes in body mass
      between the two states were taken into account. Data available on other small
      mammals are in accordance with this finding, which does not support the
      hypothesis that low-BMR mammal species increase their rate of metabolism during
      reproduction because Kleiber's relationship represents an optimal level for
      therian reproduction. Within C. russula and M. domesticus, a significant and
      negative correlation was found between the level of BMR and the change in rate of
      metabolism associated with lactation. This pattern is presumably due to the fact
      that low-BMR females undergo more extensive physiological and anatomical changes
      during lactation than high-BMR females.

PMID- 16630735
TI  - Effect of diets enriched in Delta6 desaturated fatty acids (18:3n-6 and 18:4n-3),
      on growth, fatty acid composition and highly unsaturated fatty acid synthesis in
      two populations of Arctic charr (Salvelinus alpinus L.).
AB  - This study aimed to test the hypothesis that diets containing relatively high
      amounts of the Delta6 desaturated fatty acids stearidonic acid (STA, 18:4n-3) and
      gamma-linolenic acid (GLA, 18:3n-6), may be beneficial in salmonid culture. The
      rationale being that STA and GLA would be better substrates for highly
      unsaturated fatty acid (HUFA) synthesis as their conversion does not require the
      activity of the reputed rate-limiting enzyme, fatty acid Delta6 desaturase.
      Duplicate groups of two Arctic charr (Salvelinus alpinus L.) populations with
      different feeding habits, that had been reported previously to show differences
      in HUFA biosynthetic capacity, were fed for 16 weeks on two fish meal based diets
      containing 47% protein and 21% lipid differing only in the added lipid component,
      which was either fish oil (FO) or echium oil (EO). Dietary EO had no detrimental
      effect on growth performance and feed efficiency, mortalities, or liver and flesh
      lipid contents in either population. The proportions of 18:2n-6, 18:3n-3, 18:3n
      6, 18:4n-3, 20:3n-6 and 20:4n-3 in total lipid in both liver and flesh were
      increased by dietary EO in both populations. However, the percentages of 20:5n-3
      and 22:6n-3 were reduced by EO in both liver and flesh in both strains, whereas
      20:4n-6 was only significantly reduced in flesh. In fish fed FO, HUFA synthesis
      from both [1-(14)C]18:3n-3 and [1-(14)C]20:5n-3 was significantly higher in the
      planktonivorous Coulin charr compared to the demersal, piscivorous Rannoch charr
      morph. However, HUFA synthesis was increased by EO in Rannoch charr, but not in
      Coulin charr. In conclusion, dietary EO had differential effects in the two
      populations of charr, with HUFA synthesis only stimulated by EO in the
      piscivorous Rannoch morph, which showed lower activities in fish fed FO. However,
      the hypothesis was not proved as, irrespective of the activity of the HUFA
      synthesis pathway in either population, feeding EO resulted in decreased tissue
      levels of n-3HUFA and 20:4n-6. This has been observed previously in salmonids fed
      vegetable oils, and thus the increased levels of Delta6 desaturated fatty acids
      in EO did not effectively compensate for the lack of dietary HUFA.

PMID- 16630736
TI  - When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24
      patients.
AB  - Mucolipidosis II (ML II) and Mucolipidosis type III (ML III) are autosomal
      recessive disorders of lysosomal hydrolases trafficking due to the deficiency of
      the multimeric enzyme, UDP-N-acetylglucosamine-1-phosphotransferase. The
      alpha/beta subunits encoded by the GNPTA gene is the catalytic subunit of the
      enzyme while the gamma recognition subunit is encoded by the GNPTAG gene. We
      report the molecular analysis of GNPTA in 21 families with ML II and 3 families
      with ML III. The ML II mutant genotypes included three splice-site mutations
      [IVS1-2A>G; IVS17+1G>A; IVS18+1G>A] in seven Palestinian, Israeli Arab-Muslims,
      and Turkish patients; a two base pair deletion [c.3503_4delTC] [corrected] in 11
      patients from Israel, Turkey, and Ireland; two nonsense mutations [c.2533C>T
      (Q845X); c.3613C>T (R1205X)], in a Turkish and an Arab-Muslim patient from the
      Nablus area, respectively, and an insertion mutation [c.2916insT] in a patient
      from Nablus. The ML III mutant genotypes included a splice-site mutation
      [IVS17+6T>G] in two patients from Irish/Scottish origin who were compound
      heterozygous for a nonsense mutation [c.3565C>T (R1189X)] and the deletion
      mutation [c.3503_4delTC] [corrected] respectively. The third ML III patient from
      France was compound heterozygous for a missense mutation [c.1196C>T] and the same
      deletion [c.3503_4delTC] [corrected] found homozygous in 11 ML II patients. The
      21 ML II patients were homozygous while the three ML III patients were compound
      heterozygous for mutations in GNPTA. The results of this study confirm that ML II
      or ML III phenotype is not due to the localization of the mutations, but rather
      to the severity of the mutations, ML II and ML III might be allelic, and ML III
      is genetically heterogeneous. We suggest that the diseases due to mutations in
      GNPTA represent a clinical continuum between ML III and ML II, and the
      classification of these diseases should be based on the age of onset, clinical
      symptoms, and severity.

PMID- 16630737
TI  - [Rotterdam consensus in adolescent girls: which investigations and how to
      interpret them to make the diagnosis of PCOS?].
AB  - The polycystic ovary syndrome (PCOS) is the most frequent cause of
      hyperandrogenism and anovulation in adult women as well as in adolescent girls.
      Since 2003 the diagnosis of PCOS has been based on the association of
      hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at
      ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may
      be difficult to distinguish from the symptoms of the end of puberty. Moreover,
      transvaginal ultrasound examination is seldom possible, and it is difficult to
      get precise imaging of the ovaries by abdominal route. However, the diagnosis of
      PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the
      strict application of the Rotterdam criteria, as in adult women. Priority should
      be given to clinical features whereas pelvic ultrasound must be considered as
      optional. Few hormonal assays will serve mainly to make the differential
      diagnosis, in addition to clinical findings. Once established, the diagnosis of
      PCOS in an adolescent girl must lead to the detection of the metabolic syndrome
      by means of simple investigations. This will allow early prevention of its
      complications.

PMID- 16630738
TI  - [Openness on results of assisted reproductive techniques: yes, but...].

PMID- 16630739
TI  - [Breast cancer in men: are there similarities with breast cancer in women?].
AB  - Male breast cancer is an uncommon disease although its incidence has increased
      over the recent years. Like other orphan diseases, male breast cancer is
      understudied. This disease has a lot of similarities with female breast cancer.
      Some differences are yet noticeable. This article describes three cases of
      carcinoma of the breast in men with a review of the literature on risk factors
      and treatment. A database must be started with epidemiologic information to
      understand this disease and its correlation with breast cancer in women.

PMID- 16630740
TI  - [Face presentation: retrospective study of 32 cases at term].
AB  - OBJECTIVE: To determine the etiologic factors, circumstances of diagnosis,
      obstetrical management and complications of face presentation and to value the
      maternal and foetal prognosis of this presentation. PATIENTS AND METHODS: Thirty
      two cases of face presentation have been observed in the maternity wards of Reims
      and Troyes over the last 12 years. RESULTS: The incidence of face presentation
      was 0.7 per 1000 deliveries. Spontaneous vaginal delivery occurred with mento
      anterior presentation 73% of the time and caesarean section was performed in 100%
      of mento-posterior presentation. There was no increasing rate of foetal or
      maternal mortality and morbidity with vaginal delivery. DISCUSSION AND
      CONCLUSION: Face presentation is an unusual complication of pregnancy with
      obstetric factors that predispose the foetus to face presentation. The low foetal
      and maternal mortality and morbidity substantiate the effectiveness of
      conservative management in face presentation.

PMID- 16630742
TI  - [GnRH analogues and myomas: which strategy?].

PMID- 16630743
TI  - [Hereditary predispositions to gynaecological cancers].

PMID- 16630744
TI  - Biosynthesis of C9-aldehydes in the moss Physcomitrella patens.
AB  - After wounding, the moss Physcomitrella patens emits fatty acid derived volatiles
      like octenal, octenols and (2E)-nonenal. Flowering plants produce nonenal from
      C18-fatty acids via lipoxygenase and hydroperoxide lyase reactions, but the moss
      exploits the C20 precursor arachidonic acid for the formation of these oxylipins.
      We describe the isolation of the first cDNA (PpHPL) encoding a hydroperoxide
      lyase from a lower eukaryotic organism. The physiological pathway allocation and
      characterization of a downstream enal-isomerase gives a new picture for the
      formation of fatty acid derived volatiles from lower plants. Expression of a
      fusion protein with a yellow fluorescent protein in moss protoplasts showed that
      PpHPL was found in clusters in membranes of plastids. PpHPL can be classified as
      an unspecific hydroperoxide lyase having a substrate preference for 9
      hydroperoxides of C18-fatty acids but also the predominant substrate 12
      hydroperoxy arachidonic acid is accepted. Feeding experiments using arachidonic
      acid show an increase in the 12-hydroperoxide being metabolized to C8
      aldehydes/alcohols and (3Z)-nonenal, which is rapidly isomerized to (2E)-nonenal.
      PpHPL knock out lines failed to emit (2E)-nonenal while formation of C8-volatiles
      was not affected indicating that in contrast to flowering plants, PpHPL is only
      involved in formation of a specific subset of volatiles.

PMID- 16630745
TI  - Injury in rugby league.
AB  - It was the purpose of this review to document the range, incidence, location and
      mechanism of injury occurring in the sport of rugby league. Rugby league is a
      collision sport played in Europe and the Pacific regions including Australia. The
      sport is well established and has competitions ranging from junior to elite
      professional. Due to the contact nature of the game, injury is relatively common.
      The most common injuries are musculotendinous in nature and afflict the lower
      limb more frequently than elsewhere. Despite the high incidence of minor
      (sprains/strains) to moderate musculoskeletal injury (fracture, ligament and
      joint injury) and minor head injuries such as lacerations, nasal fractures and
      concussions, rare more serious spinal cord and other injuries causing death have
      also been recorded. The literature on rugby league injury is small but growing
      and suffers from a lack of consistent definition of what an injury is, thereby
      causing variability in the nature and incidence/prevalence of injury. Information
      is lacking on the injury profiles of different age groups. Importantly, there has
      been little attempt to establish a coordinated injury surveillance program in
      rugby league in the junior or professional levels. The implementation of such
      programs would require a universal definition of injury and a focus on important
      events and competitions. The implementation could provide important information
      in the identification and prevention of risk factors for injury.

PMID- 16630746
TI  - Effects of number of eccentric muscle actions on first and second bouts of
      eccentric exercise of the elbow flexors.
AB  - This study compared changes in indirect markers of muscle damage following
      eccentric exercise of the elbow flexors among the exercises consisting of
      different number of eccentric actions. Sixty male athletes were placed into one
      of the six groups (n=10 per group) based on the number of eccentric actions for
      the first (ECC1) and second exercise bouts (ECC2). Single bout groups (30, 50,
      and 70) performed ECC1 only, and repeated bout groups (30-30, 50-50, and 70-70)
      performed ECC2 3 days after ECC1. Another 10 male athletes performed different
      number of eccentric actions for ECC1 (30) and ECC2 (70) separated by 3 days (30
      70). Changes in maximal isometric strength (MVC), range of motion (ROM), upper
      arm circumference (CIR), serum creatine kinase activity, myoglobin, and nitric
      oxide concentrations and muscle soreness for 10 days following ECC1 were compared
      among groups by two-way repeated measures ANOVA. Changes in MVC, ROM, and CIR
      following ECC1 were significantly (P<0.05) smaller for the groups that performed
      30 eccentric actions compared with other groups. No significant differences
      between 30 and 30-30, 50 and 50-50, and 70 and 70-70 were evident for the changes
      in the measures for 10 days following ECC1 except for the acute decreases in MVC
      and ROM immediately after ECC2 for the repeated bout groups. The 30-30 and 30-70
      groups showed similar changes in all criterion measures. It is concluded that
      recovery from eccentric exercise is not retarded by the second bout of eccentric
      exercise regardless of the number of eccentric actions.

PMID- 16630747
TI  - Simultaneous electroencephalography and functional magnetic resonance imaging
      applied to epilepsy.
AB  - Among the recent advances in neuroimaging and clinical neurophysiology,
      simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI), that is SEM, stands apart as a challenging integration of
      techniques with great potential to provide unique information. The benefit of
      this integration is the utilization of each technique's strengths: the high
      temporal resolution and sensitivity to epileptic abnormalities of EEG and the
      high spatial resolution and noninvasive localization of cerebral metabolic change
      of fMRI. With SEM, electroencephalographic events that occur during fMRI may be
      identified and subsequently mapped with high resolution according to the
      hemodynamic changes that accompany them. Reaching the point of technically
      reliable SEM has required solutions to the many safety and electrical noise
      problems inherent to this technique. Recording an electroencephalogram during MRI
      requires special, MRI-compatible EEG equipment and a means to identify the low
      amplitude electroencephalographic signal within an electrically noisy
      environment. With the results obtained at several institutions, SEM is now at a
      point in its development where the understanding of its validity as an indicator
      of the epileptic irritative and ictal-onset zones can be expanded. Because of its
      integration of both electrophysiologic and metabolic information, SEM also may be
      used to gain a greater understanding of cerebral physiology, in general, and
      fundamental aspects of epilepsy, in particular.

PMID- 16630748
TI  - Effect of eprosartan on the sympathetic response to cold pressor test in healthy
      volunteers.
AB  - The aim of this study was to evaluate the effect of short-term administration of
      the AT1 angiotensin II receptor antagonist, eprosartan, on the sympathetic
      response to cold pressor test (CPT) in normotensive healthy volunteers. Sixty
      nine healthy volunteers were included in this double-blind placebo-controlled
      study. Blood pressure and heart rate were determined before and 175 min after
      oral administration of placebo, losartan (50 mg) or eprosartan (600 mg).
      Immediately, the subjects underwent CPT and then the same hemodynamic variables
      were measured. CPT increased arterial blood pressure (systolic, diastolic and
      mean) and HR in placebo-treated group. Pretreatment with a single dose of
      losartan or eprosartan blunted CPT-induced pressor response, but not the rise in
      heart rate. Our results demonstrate that endogenous angiotensin II, through
      stimulation of AT1 receptor, supports sympathetic mediated stress-response in
      humans.

PMID- 16630749
TI  - Xtn3 is a developmentally expressed cardiac and skeletal muscle-specific novex-3
      titin isoform.
AB  - Titin proteins play an essential role in maintaining muscle function and
      structure. Recent work has implicated the involvement of the novex-3 titin
      isoform in sarcomere restructuring and disease. Unlike avian and mammalian
      systems, Xenopus laevis myogenesis is characterized by a wave of primary
      myogenesis followed by apoptosis of the primary muscles and formation of new
      muscles by secondary myogenesis. We show here that the Xenopus laevis novex-3
      titin isoform (Xtn3) is developmentally expressed throughout the somites, heart,
      and primary muscles of the developing embryo. Downregulation of Xtn3 expression
      at tadpole stages appears to coincide with the change in myofiber composition
      from solely embryonic "fast" fiber types to myofibers containing both "fast" and
      "slow" fiber types. We demonstrate that Xtn3 is expressed early in the presomitic
      mesoderm and remains expressed in the somites, ventral myoblasts, and developing
      jaw muscles through late tailbud stage. Furthermore, we show that Xtn3 is
      expressed in the cardiac primordia prior to linear heart tube formation and
      remains expressed in the heart until tadpole stage, at which point it is
      downregulated in the heart except in discrete patches of cardiac cells. Finally,
      we demonstrate that Xtn3 transcripts are detectable in adult heart and muscle
      tissues.

PMID- 16630750
TI  - Lipotoxicity, overnutrition and energy metabolism in aging.
AB  - The safest place to store lipids is the white adipose tissue, but its storage
      capacity may become saturated resulting in excess of fat "overspilled" to non
      adipose tissues. This overspill of fat occurs in apparently opposite pathological
      states such as lipodistrophy or obesity. When the excess of energy is redirected
      towards peripheral organs, their initial response is to facilitate the storage of
      the surplus in the form of triacylglycerol, but the limited triacylglycerol
      buffer capacity becomes saturated soon. Under these conditions excess of lipids
      enter alternative non-oxidative pathways that result in production of toxic
      reactive lipid species that induce organ-specific toxic responses leading to
      apoptosis. Reactive lipids can accumulate in non-adipose tissues of metabolically
      relevant organs such as pancreatic beta-cells, liver, heart and skeletal muscle
      leading to lipotoxicity, a process that contributes substantially to the
      pathophysiology of insulin resistance, type 2 diabetes, steatotic liver disease
      and heart failure. The effects of this lipotoxic insult can be minimised by
      several strategies: (a) decreased incorporation of energy, (b) a less orthodox
      approach such as increased adipose tissue expandability and/or (c) increased
      oxidation of fat in peripheral organs. Aging should be considered as
      physiological degenerative process potentially accelerated by concomitant
      lipotoxic insults. Conversely, the process of aging can sensitise cells to
      effects of lipid toxicity.

PMID- 16630751
TI  - Kinetic study on the irreversible thermal denaturation of Schistosoma japonicum
      glutathione S-transferase.
AB  - The thermal unfolding pathway of the Schistosoma japonicum glutathione S
      transferase (Sj26GST) was previously interpreted by applying equilibrium
      thermodynamics and a reversible two-state model (Kaplan et al., (1997) Protein
      Science, 6, 399-406), though weak support for this interpretation was provided.
      In our study, thermal denaturation of Sj26GST has been re-examined by
      differential scanning calorimetry in the pH range of 6.5-8.5 and in the presence
      of the substrate and S-hexylglutathione. Calorimetric traces were found to be
      irreversible and highly scan-rate dependent. Thermogram shapes, as well as their
      scan-rate dependence, can be globally explained by assuming that thermal
      denaturation takes place according to one irreversible step described by a first
      order kinetic constant that changes with temperature, as given by an Arrhenius
      equation. On the basis of this model, values for the rate constant as a function
      of temperature and the activation energy have been determined. Data also indicate
      that binding of GSH or S-hexylglutathione just exert a very little stabilising
      effect on the dimeric structure of the molecule.

PMID- 16630752
TI  - Proton pump inhibitors and acute interstitial nephritis.
AB  - BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are a widely prescribed class of
      drugs, and their usage worldwide is increasing. Although well-tolerated, there
      have been case reports and a recent case series implicating these drugs in acute
      interstitial nephritis (AIN) and progression to acute renal failure (ARF). The
      aim of this study was to investigate how widespread this complication is in
      Australia, to identify which PPIs are implicated, and to establish whether PPI
      induced AIN is a class effect. METHODS: We undertook a retrospective case review
      of potential cases at 2 teaching hospitals and a review of registry data from the
      Therapeutic Goods Administration of Australia (TGA). Parameters sought included
      the drug implicated, concurrent medications, symptoms, signs, serum creatinine,
      and time of onset after prescription. RESULTS: We identified 18 cases of biopsy
      proven PPI-induced AIN causing ARF in the retrospective case review, which is the
      largest hospital-based case series to date. The TGA registry data identified an
      additional 31 cases of "biopsy proven interstitial nephritis." An additional 10
      cases of "suspected interstitial nephritis," 20 cases of "unclassified acute
      renal failure," and 26 cases of "renal impairment" were also identified. All 5
      commercially available PPIs were implicated in these cases. CONCLUSION: With the
      ever more widespread use of this class of medications, PPI-induced AIN is likely
      to become more frequent. There is now evidence to incriminate all the
      commercially available PPIs, suggesting there is a class effect. Failure to
      recognize this entity might have catastrophic long-term consequences including
      chronic kidney disease. Increased awareness might facilitate more rapid diagnosis
      and management of this potentially reversible condition.

PMID- 16630753
TI  - Hereditary fructose intolerance and celiac disease: a novel genetic association.
AB  - BACKGROUND & AIMS: Celiac disease (CD) has been associated with several genetic
      disorders, but has not been associated with hereditary fructose intolerance
      (HFI). METHODS: We identified CD in 4 female patients affected by HFI from among
      38 Italian HFI patients. RESULTS: Three of these patients were children in whom
      the CD-associated signs were hypertransaminasemia, failure to thrive, low weight,
      and short stature, whereas the adult patient had protracted diarrhea
      notwithstanding a fructose-free diet. The incidence of CD in our group of HFI
      patients was higher (>10%) than in the general population (1%-3%) (P<.02).
      CONCLUSIONS: The possibility of an association between these 2 gastrointestinal
      disorders is important, particularly in the management of HFI patients with
      persisting symptoms.

PMID- 16630754
TI  - A case of iron-deficiency anemia.

PMID- 16630755
TI  - Therapeutic options for gastrointestinal carcinoids.
AB  - Although wide surgical resection is the optimal curative therapy for carcinoid
      tumors, in most patients the presence of metastatic disease at diagnosis usually
      renders excision a palliative procedure. This nevertheless decreases tumor
      burden, facilitates symptom control, and prevents complications caused by
      bleeding, perforation, or bowel obstruction resulting from fibrosis. In the
      stomach (types I and II) and rectum endoscopic excision may be adequate provided
      the lesion(s) are local. Long-term therapy is focused on symptom alleviation and
      improvement of quality of life using somatostatin analogues, particularly in a
      subcutaneous depot formulation. In some instances interferons may have a role but
      their usage often is associated with substantial adverse events. Conventional
      chemotherapy and external radiotherapy either alone or in a variety of
      permutations are of minimal efficacy and should be balanced against the decrease
      in quality of life often engendered by such agents. Hepatic metastases may be
      amenable to surgery, radiofrequency ablation, or embolization either alone or in
      combination with chemotherapeutic agents or isotopically loaded microspheres.
      Rarely hepatic transplantation may be of benefit although controversy exists as
      to its actual use. Peptide-receptor-targeted radiotherapy for advanced disease
      using radiolabeled octapeptide analogs (111In/90Yt/177Lu-octreotide) appear
      promising but data are limited and its status remains investigational. A variety
      of antiangiogenesis and growth factor-targeted agents have been evaluated, but as
      yet have shown little promise. The keystone of current therapy remains the long
      acting somatostatin analogues that alleviate symptomatology and substantially
      improve quality of life with minimal adverse effects.

PMID- 16630756
TI  - Multiple microhamartomas of the biliary tract system: Von Meyenburg Complexes.

PMID- 16630757
TI  - Abscess of the caudate lobe of liver with spontaneous peritoneal rupture.

PMID- 16630758
TI  - Noncardiac chest pain.

PMID- 16630759
TI  - Diagnostic value of C-reactive protein for predicting activity level of Crohn's
      disease.
AB  - BACKGROUND AND AIMS: Measuring Crohn's disease (CD) activity is useful in
      clinical trials as well as in clinical practice, but each available instrument to
      measure such activity has some limitations. C-reactive protein (CRP) is a
      sensitive marker for inflammation and tissue injury. The aims of the study were:
      to assess the diagnostic value of low level of CRP for predicting a low CD
      activity, and to calculate optimal CRP cutoff value for selecting patients with
      moderate or high CD activity. METHODS: One hundred fifty consecutive patients
      with active or nonactive CD were included in the study without any pre-selection
      criteria. CRP was measured, and CD activity was calculated by means of the van
      Hees index (VHI). RESULTS: The median VHI score was 154.4 (interquartile range,
      126.0-193.4), and the median CRP was 19.1 mg/L (interquartile range, 6.1-50.1
      mg/L; upper limit of normal [N], 4 mg/L). Forty-nine percent of our patients had
      CRP >20 mg/L. CRP was significantly correlated to VHI (P = .0001). The
      probability that VHI was <150 if CRP was below upper limit of normal was equal to
      1 (confidence interval, 0.891-1.000). The diagnostic value for CRP predicting a
      VHI > or =150 was high; the area under the receiver operating characteristic
      curve was equal to 0.844 (confidence interval, 0.783-0.906; P = .0001) with an
      optimal cutoff value of 21.6 mg/L, about 5 x N. CONCLUSIONS: CRP appears useful
      to evaluate CD activity, especially to predict inactive or low activity CD.

PMID- 16630760
TI  - Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase
      antibody for the diagnosis of celiac disease.
AB  - BACKGROUND & AIMS: The diagnosis of celiac disease often relies on the anti
      tissue transglutaminase (tTG) antibody test. The aim of this study was to
      evaluate its sensitivity and specificity in clinical practice with the use of
      commercial laboratories, in which the test characteristics might differ from
      research laboratories. METHODS: We identified 122 patients with suspected celiac
      disease who had anti-tTG antibody serologies as well as upper endoscopy with
      duodenal biopsies. Those with celiac disease were classified as either classic
      (with diarrhea or other symptoms of malabsorption) or silent (asymptomatic).
      Biopsies from celiac disease patients were classified as either partial (Marsh
      IIIA) or total (Marsh IIIB or IIIC) villous atrophy. RESULTS: The overall
      sensitivity, specificity, and positive and negative predictive values of the anti
      tTG antibody test were 70.6%, 65.0%, 91.1%, and 30.2%, respectively. The
      sensitivity was 90.0% for patients with total villous atrophy and 42.3% for
      patients with partial villous atrophy (P < .0001). There were differences in both
      sensitivity and specificity between the 2 most commonly used commercial
      laboratories. The sensitivity for Lab #1 was 40.0% versus 86.4% for Lab #2 (P <
      .0001). The specificity for Lab #1 was 100.0%, and it was 41.7% for Lab #2 (P =
      .02). CONCLUSIONS: The sensitivity of the anti-tTG antibody in clinical practice
      is not as high as previously reported in research laboratories. The sensitivity
      is significantly lower in patients with partial villous atrophy. There is also
      significant variability in test characteristics among major commercial
      laboratories in the United States. These results need to be confirmed in
      prospective studies.

PMID- 16630761
TI  - Dysplasia and cancer in a large multicenter cohort of patients with Barrett's
      esophagus.
AB  - BACKGROUND & AIMS: The exact incidence of adenocarcinoma in patients with
      Barrett's esophagus (BE) is not known and is reported to vary from 0.2%-2% per
      year. Published series of patients with BE have included relatively small numbers
      of patients with limited duration of follow-up. The goal of this study was to
      define the prevalence and incidence of dysplasia and cancer and evaluate the
      paths of progression in a large multicenter cohort of BE patients. METHODS: The
      BE study is a multicenter clinical and endoscopic outcomes project involving a
      single large database of patients with BE. Data from each of the participating
      centers were merged into the main study database. Cancers and HGD occurring
      within 12 months of the index endoscopy were regarded as prevalent cases.
      RESULTS: One thousand three hundred seventy-six patients met the study criteria
      (95% white, 14% women); 91 patients had cancer at the initial endoscopy
      (prevalent cases, 6.7%; 95% confidence interval [CI], 4.8%-8.7%). Six hundred
      eighteen patients were followed for a total of 2546 patient-years; mean follow-up
      was 4.12 years. Twelve patients developed cancer during follow-up, a cancer
      incidence of 1 in 212 patient-years of follow-up (0.5% per year; 95% CI, 0%
      1.1%). The combined incidence of HGD and/or cancer was 1 in 75 patient-years of
      follow-up or 1.3% per year (95% CI, 0%-2.2%). Of the 34 patients developing HGD
      and/or cancer, 18 patients (53%) had at least 2 initial consecutive endoscopies
      with biopsies revealing nondysplastic mucosa. The incidence of LGD was 4.3% per
      year (95% CI, 2.8%-6.0%). In the 156 patients with LGD, regression to no
      dysplasia occurred in 66%, persistent LGD in 21%, and progression to HGD/cancer
      in 13%. The incidence of cancer in patients with LGD was 1 in 156 patient-years
      of follow-up or 0.6% per year (95% CI, 0%-1.3%). CONCLUSIONS: Preliminary results
      from this trial define the prevalence and incidence of dysplasia and cancer in a
      multicenter cohort of patients with BE. At least half the patients who developed
      HGD and/or cancer had 2 consecutive initial endoscopies with biopsies revealing
      nondysplastic mucosa. The majority of patients with LGD regressed and had a
      cancer incidence similar to all BE patients.

PMID- 16630762
TI  - The Manitoba Inflammatory Bowel Disease Cohort Study: prolonged symptoms before
      diagnosis--how much is irritable bowel syndrome?
AB  - BACKGROUND & AIMS: The Manitoba Inflammatory Bowel Disease (IBD) Cohort Study is
      a population-based prospective cohort study of recently diagnosed IBD (n=396). At
      enrollment, 162 (41%) indicated gastrointestinal symptom>or=3 years before
      diagnosis. We aimed to determine whether coexistence of irritable bowel syndrome
      (IBS) had a role in symptoms before IBD diagnosis. METHODS: Patients were
      interviewed about symptoms and investigations before IBD diagnosis. Patients were
      assessed retrospectively for preexisting IBS. RESULTS: Of 112 patients
      interviewed, 58% had Crohn's disease, 37% UC, 3% proctitis, and 2% indeterminant
      colitis. Symptoms at IBD diagnosis were considered the same (7%), worse (43%),
      different (20%), or both worse and different (30%) than at initial onset. Mean
      time between initial symptoms and diagnosis was 11 years (range, 3-48 years).
      Increasing age at IBD diagnosis correlated with a longer period after initial
      symptoms and diagnosis of IBD (r=.32, P<.0001). Gender and specific IBD diagnosis
      had no effect on this time period. Patients were identified as no previous IBS
      (51%), likely IBS (25%), and possible IBS (24%). Those with likely and possible
      IBS had a trend toward longer symptom duration before IBD diagnosis than those
      without IBS (P=.07). Of the total IBD cohort (n=396), considering only those with
      symptoms for >or=3 years before diagnosis, 14% were considered to have likely or
      possible IBS. CONCLUSIONS: These data suggest that older patients and those with
      likely and possible preexisting IBS are more likely to experience longer symptom
      duration before diagnosis of IBD. The prevalence rate of IBS was similar to
      estimated base rates in the general population.

PMID- 16630763
TI  - Influence of the number of malignant regional lymph nodes detected by endoscopic
      ultrasonography on survival stratification in esophageal adenocarcinoma.
AB  - BACKGROUND & AIMS: The nodal staging of esophageal cancer accounts for the
      absence or presence of metastatic lymph nodes (N0 or N1, respectively). Surgical
      data suggest that patients have worse survival when esophagectomy specimens
      contain higher numbers of regional malignant lymph nodes. It has been proposed
      that the staging system for esophageal cancer be modified to include the number
      of malignant lymph nodes. The aim of this study was to determine the influence of
      the number of malignant-appearing regional lymph nodes detected on endoscopic
      ultrasonography (EUS) on survival in patients with esophageal adenocarcinoma.
      METHODS: Historical case series involved patients with esophageal adenocarcinoma
      who underwent EUS staging at a single center between 1994 and 2004. Endoscopy
      reports were reviewed to determine the number of malignant-appearing
      periesophageal lymph nodes seen on EUS examination. Subjects were categorized as
      having 0, 1-2, or >2 periesophageal lymph nodes. A regional cancer registry
      prospectively obtained survival data. RESULTS: Among 85 patients with esophageal
      adenocarcinoma, the Kaplan-Meier curves showed distinct survival advantages in
      those with fewer malignant-appearing regional lymph nodes (P=.0008). The median
      survivals were 66 months, 14.5 months, and 6.5 months for 0, 1-2, and >2
      malignant-appearing lymph nodes, respectively. Survival was also influenced by
      celiac lymph nodes and tumor length, both of which were associated with increased
      number of malignant nodes. CONCLUSIONS: The number of malignant-appearing
      periesophageal lymph nodes detected by EUS is associated with improved survival
      stratification in patients with esophageal adenocarcinoma and should be
      considered in the presurgical staging of esophageal cancer.

PMID- 16630764
TI  - Choledochocele, diverticular subtype.

PMID- 16630765
TI  - Unraveling intestinal malrotation with 3-dimensional computed tomography.

PMID- 16630766
TI  - Symptoms and quality of life in community women with fecal incontinence.
AB  - BACKGROUND & AIMS: Assessments of symptom severity are necessary to guide therapy
      in fecal incontinence (FI). However, there is no consensus on how self-reported
      symptom severity in FI should be measured for this purpose, and the relationship
      between symptoms of FI and its impact on quality of life (QOL) is not known.
      METHODS: A questionnaire was mailed to an age-stratified random sample of 5300
      women identified through the Rochester Epidemiology Project. Symptom severity was
      assessed by a validated scale (Fecal Incontinence and Constipation Assessment
      [FICA]), and impact on 15 domains of QOL was evaluated for subjects who had any
      FI during the past year. The scale incorporated the type, frequency, and amount
      of FI, as well as the circumstances surrounding FI (ie, urge or passive FI). A
      QOL-weighted symptom severity score was derived by weighting the responses for
      these characteristics, in each subject, by the average QOL impact for all
      subjects who reported that specific symptom characteristic. The relationship
      between symptom severity and the QOL-weighted symptom severity score was assessed
      by Spearman rank correlation. RESULTS: Altogether, 2800 of 5300 (53%) women
      responded to the survey. FI symptoms were mild (45%), moderate (50%), or severe
      (5%). Among women with FI, the FICA symptom severity scale was strongly
      correlated (r(s) = 0.92, P < .0001) with the QOL-weighted symptom severity score.
      CONCLUSIONS: Among unselected women in the community, self-reported symptom
      severity, rated by the FICA scale, was strongly correlated with the impact of FI
      on QOL, supporting the use of this scale to assess symptom severity in FI.

PMID- 16630767
TI  - Primary malignant fibrous histiocytoma of the colon.

PMID- 16630768
TI  - Iron-deficiency anemia caused by hookworm infestation.

PMID- 16630769
TI  - Recurrent upper-gastrointestinal bleeding from multiple gastric polyps treated
      successfully by endoscopic mucosal resection.

PMID- 16630770
TI  - Chronic hepatitis C in patients with persistently normal alanine transaminase
      levels.
AB  - BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have
      persistently normal serum alanine transaminase (ALT) levels. We compared
      characteristics of chronic hepatitis C patients with patients with normal and
      elevated ALT levels using data from 3 randomized phase III trials of
      peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with
      normal ALT values (on >or=3 occasions without any increases in ALT level over a 6
      to 18-month period) and 1993 patients with elevated ALT levels were compared.
      Sixty-eight of the 480 patients with normal ALT levels were randomized to no
      treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT
      levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The
      serum HCV RNA titer was significantly lower in patients with normal ALT levels
      (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels
      had significantly lower inflammation and fibrosis scores on liver biopsy
      examination than patients with elevated ALT levels, but almost two-thirds had
      portal fibrosis and 10% had bridging fibrosis. No correlation between baseline
      ALT activity, HCV RNA level, and liver histology was observed in patients with
      normal ALT levels. During the 72-week follow-up period, ALT activity elevated
      above the upper limit of normal in 53% of the untreated patients with normal
      levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C
      patients with normal ALT levels should be evaluated in a similar manner as
      patients with elevated ALT levels because they are at risk for developing
      significant liver disease. The decision to treat with peginterferon alfa and
      ribavirin should be based on multiple factors, rather than on ALT levels alone.

PMID- 16630771
TI  - A double-blind randomized placebo-controlled trial of orlistat for the treatment
      of nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Few controlled studies have addressed the issue of effective
      medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein
      assessed the effect of orlistat in patients with NAFLD. METHODS: We performed a
      randomized, double-blind, placebo-controlled study on 52 patients with NAFLD
      diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The
      patients were randomized to receive either orlistat (120 mg 3 times daily for 6
      months) or placebo. All patients participated in an identical behavioral weight
      loss program. All patients underwent monthly evaluation by abdominal US; liver
      enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were
      monitored, and all patients underwent nutritional follow-up evaluation. Twenty
      two patients underwent a second liver biopsy examination at the end of the study.
      RESULTS: Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body
      mass index, 33) completed the study. Serum glucose and insulin levels (P<.03)
      were significantly higher in the orlistat group, which also presented a higher
      degree of fibrosis. Body mass index was reduced significantly in each group, with
      a nonsignificant difference between the groups. Serum alanine transaminase (ALT)
      levels decreased significantly in both groups, with an almost 2-fold reduction in
      the orlistat group (48% vs 26.4%). There was a statistically significant reversal
      of fatty liver by US only in the orlistat group (P<.05). CONCLUSIONS: Orlistat
      improves serum ALT levels and steatosis on US in NAFLD patients, beyond its
      effect on weight reduction.

PMID- 16630772
TI  - Duodenal intraepithelial lymphocytes in inflammatory disorders of the esophagus
      and stomach.
AB  - BACKGROUND & AIMS: Duodenal cluster designation 3 positive (CD3+) intraepithelial
      T lymphocytes (IELs) are increased in gluten-sensitive enteropathy (GSE) and,
      because of the dispersed nature of the gut immune system, might also be increased
      in mucosa distant from the duodenum. Conversely, little is known about their
      frequency in the duodenum during inflammatory conditions of the stomach and
      esophagus. This study assessed whether CD3+ IELs are increased in duodenal
      biopsies in patients with esophagitis or gastritis relative to normal control
      subjects. METHODS: Cases (n=46) with concurrent mucosal biopsies of the duodenum,
      stomach, and esophagus were divided into 4 groups: I, no inflammation in any
      site; II, active esophagitis only; III, chronic active gastritis only, with
      Helicobacter pylori bacteria; IV, chronic gastritis only, without H pylori
      bacteria. Immunostains against CD3 were performed by using standard techniques,
      the number of CD3+ cells/100 enterocytes in 3 well-oriented villi was recorded,
      and the results for the groups were compared statistically. RESULTS: The average
      number of CD3+ IELs/100 enterocytes for each group was I, 6.7; II, 11.8; III,
      7.2; and IV, 9.1. The differences among the groups were not statistically
      significant. There was no correlation between the number of duodenal IELs and
      severity of inflammation, patient age or sex, or symptoms. CONCLUSIONS: Duodenal
      mucosal biopsies from patients with esophagitis and/or gastritis may have a
      slightly increased number of CD3+ IELs relative to normal control subjects. This
      finding may reflect an underlying mechanism of diffuse inflammation in the
      gastrointestinal tract.

PMID- 16630773
TI  - Mechanistic associations of a mild phenotype of immunodysregulation,
      polyendocrinopathy, enteropathy, x-linked syndrome.
AB  - BACKGROUND & AIMS: The syndrome of immunodysregulation, polyendocrinopathy,
      enteropathy, X-linked (IPEX) is a rare disorder resulting in the expression of
      multiple autoimmune and allergic features. Early onset enteropathy and type 1
      diabetes (T1D) are the most common clinical features. The IPEX syndrome is caused
      by mutations of the FOXP3 gene, which is essential for the development of
      regulatory T cells (Treg). We describe 2 unrelated patients with IPEX syndrome
      with a mild clinical phenotype and with novel FOXP3 mutations and the phenotypic
      and functional characterization of their Treg cells. METHODS: The FOXP3 gene was
      analyzed by sequencing amplimers from genomic DNA. Treg cells were characterized
      by evaluating the number of CD4+CD25+ T cells and their functional ability to
      suppress the proliferation of autologous CD4+CD25- effector T cells stimulated
      with anti-CD3 and anti-CD28 antibodies. RESULTS: A 7-year-old boy and a 24-year
      old man presented with autoimmune enteropathy characterized by early onset
      persistent diarrhea not associated with T1D or other endocrinopathies. These 2
      patients carry novel FOXP3 mutations that do not abrogate the function of the
      forkhead domain. They have normal numbers of CD4+CD25+ T lymphocytes, however,
      these show severely defective suppressive function in vitro. CONCLUSIONS: Our 2
      patients show that IPEX patients may present with early onset enteropathy and
      long-term survival without T1D or other endocrinopathies. This milder phenotype
      may be associated with FOXP3 mutations that do not abrogate the function of the
      forkhead domain.

PMID- 16630774
TI  - Brunner's gland hamartoma.

PMID- 16630775
TI  - Abdominal cocoon syndrome.

PMID- 16630776
TI  - The long-term efficacy of pneumatic dilatation and Heller myotomy for the
      treatment of achalasia.
AB  - BACKGROUND & AIMS: Studies comparing long-term success after pneumatic dilatation
      (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long
      term outcome of PD (single dilatation and graded approach) and laparoscopic HM
      and identifies risk factors for treatment failure. METHODS: A cross-sectional
      follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was
      followed-up for a mean of 3.1 years. There was a total of 106 patients treated by
      graded PD (1-3 dilatations with progressively larger balloons) and 73 patients
      treated by HM (20 had failed graded PD and crossed over to HM). A symptom
      assessment (structured telephone interview or clinic visit) was performed and
      patients were given freedom from alternative therapies to determine treatment
      outcome. Endoscopy, manometry, and timed barium esophagram were performed to
      determine the cause of treatment failure. RESULTS: The success of single PD was
      defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk
      factors for failure: younger age, male sex, wider esophagus, and poor emptying on
      posttreatment timed barium esophagram). Freedom from subsequent PDs increased
      with each dilatation (graded PD). The success of graded PD and HM, defined as
      dysphagia/regurgitation less than 3 times/wk or freedom from alternative
      treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk
      factors for failure were identified). Causes of symptom recurrence were
      incompletely treated achalasia (96% after PD vs 64% after HM) and
      gastroesophageal reflux disease (4% after PD vs 36% after HM). CONCLUSIONS: No
      treatment cures achalasia. Short- and long-term success is similar for graded PD
      and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia
      patients need careful long-term follow-up evaluation.

PMID- 16630805
TI  - Janelia Farm: an experiment in scientific culture.
AB  - Janelia Farm, the new research campus of the Howard Hughes Medical Institute, is
      an ongoing experiment in the social engineering of research communities.

PMID- 16630806
TI  - Histone lysine demethylases and their impact on epigenetics.
AB  - Methylation marks on the lysine residues of histone proteins are thought to
      contribute to epigenetic phenomena in part because of their apparent
      irreversibility. Will this view change with the recent discovery of histone
      lysine demethylases that reversibly remove methyl marks?

PMID- 16630807
TI  - Bent out of shape: RNA unwinding by the DEAD-box helicase Vasa.
AB  - RNA helicases of the DEAD-box family are involved in essentially all RNA
      dependent cellular processes. In this issue of Cell, Sengoku et al. (2006) solve
      the structure of the DEAD-box protein Vasa in the presence of RNA and a
      nonhydrolyzable ATP analog and provide important insights into how this family of
      helicases unwinds RNA.

PMID- 16630808
TI  - Nck links nephrin to actin in kidney podocytes.
AB  - Two papers, one in Nature (Jones et al., 2006) and the other in the Journal of
      Clinical Investigation (Verma et al., 2006) show that Nck adaptor proteins
      connect phosphorylated nephrin with actin polymerization in podocyte foot
      processes, structures important for slit-diaphragm formation in the kidney. Their
      results further our understanding of podocyte development and repair in
      glomerular disease.

PMID- 16630809
TI  - When a motor goes bad: a kinesin regulates neuronal survival.
AB  - In this issue of Cell, Midorikawa et al. (2006) demonstrate that the kinesin
      superfamily member KIF4, a microtubule-based molecular motor, regulates the
      survival of electrically active neurons in the developing brain by modulating the
      function of poly(ADP-ribose) polymerase-1 in an unexpected way.

PMID- 16630810
TI  - Toxoplasma: guess who's coming to dinner.
AB  - In this issue of Cell, Coppens and coworkers (Coppens et al., 2006) describe how
      Toxoplasma gondii, an obligate intracellular parasite, feeds on the host. Coppens
      et al. provide evidence that the parasite takes host cell endosomes and lysosomes
      hostage by sequestering them where the parasite resides, within invaginations of
      the parasitophorous vacuole.

PMID- 16630811
TI  - Pten, tumorigenesis, and stem cell self-renewal.
AB  - Self-renewal pathways crucial for maintaining stem cells are deregulated in
      cancer, raising the spectre that cancer therapies targeting such pathways might
      also ablate normal stem cells. As Yilmaz et al. (2006) report in a recent Nature
      paper, this may not be the case for the tumor suppressor protein Pten, which
      drives the self-renewal of normal hematopoietic stem cells and the formation of
      leukemia cells through different mechanisms.

PMID- 16630812
TI  - Searching chromatin for stem cell identity.
AB  - Stem cells encapsulate the fundamental problem of metazoan biology in miniature:
      How do cells establish and maintain their fates? Increasing evidence indicates
      that stem cell chromatin activates proliferation genes and represses
      differentiation genes. Understanding how these configurations are stabilized by
      Polycomb group proteins will advance our understanding of embryonic development,
      tissue homeostasis, regeneration, aging, and oncogenesis.

PMID- 16630813
TI  - Bacterially speaking.
AB  - Bacteria use a variety of means to communicate with one another and with their
      eukaryotic hosts. In some cases, social interactions allow bacteria to
      synchronize the behavior of all of the members of the group and thereby act like
      multicellular organisms. By contrast, some bacterial social engagements promote
      individuality among members within the group and thereby foster diversity. Here
      we explore the molecular mechanisms underpinning some recently discovered
      bacterial communication systems. These include long- and short-range chemical
      signaling channels; one-way, two-way, and multi-way communication; contact
      mediated and contact-inhibited signaling; and the use and spread of
      misinformation or, more dramatically, even deadly information.

PMID- 16630814
TI  - FSH directly regulates bone mass.
AB  - Postmenopausal osteoporosis, a global public health problem, has for decades been
      attributed solely to declining estrogen levels. Although FSH levels rise sharply
      in parallel, a direct effect of FSH on the skeleton has never been explored. We
      show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH
      receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass
      is increased and osteoclastic resorption is decreased in haploinsufficient
      FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action
      of FSH is estrogen independent. Osteoclasts and their precursors possess
      G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in
      enhanced osteoclast formation and function. We suggest that high circulating FSH
      causes hypogonadal bone loss.

PMID- 16630815
TI  - Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar
      space.
AB  - The intracellular compartment harboring Toxoplasma gondii satisfies the
      parasite's nutritional needs for rapid growth in mammalian cells. We demonstrate
      that the parasitophorous vacuole (PV) of T. gondii accumulates material coming
      from the host mammalian cell via the exploitation of the host endo-lysosomal
      system. The parasite actively recruits host microtubules, resulting in selective
      attraction of endo-lysosomes to the PV. Microtubule-based invaginations of the PV
      membrane serve as conduits for the delivery of host endo-lysosomes within the PV.
      These tubular conduits are decorated by a parasite coat, including the
      tubulogenic protein GRA7, which acts like a garrote that sequesters host
      endocytic organelles in the vacuolar space. These data define an unanticipated
      process allowing the parasite intimate and concentrated access to a diverse range
      of low molecular weight components produced by the endo-lysosomal system. More
      generally, they identify a unique mechanism for unidirectional transport and
      sequestration of host organelles.

PMID- 16630816
TI  - Synergistic functions of SII and p300 in productive activator-dependent
      transcription of chromatin templates.
AB  - We have reconstituted a highly purified RNA polymerase II transcription system
      containing chromatin templates assembled with purified histones and assembly
      factors, the histone acetyltransferase p300, and components of the general
      transcription machinery that, by themselves, suffice for activated transcription
      (initiation and elongation) on DNA templates. We show that this system mediates
      activator-dependent initiation, but not productive elongation, on chromatin
      templates. We further report the purification of a chromatin transcription
      enabling activity (CTEA) that, in a manner dependent upon p300 and acetyl-CoA,
      strongly potentiates transcription elongation through several contiguous
      nucleosomes as must occur in vivo. The transcription elongation factor SII is a
      major component of CTEA and strongly synergizes with p300 (histone acetylation)
      at a step subsequent to preinitiation complex formation. The purification of CTEA
      also identified HMGB2 as a coactivator that, while inactive on its own, enhances
      SII and p300 functions.

PMID- 16630817
TI  - Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa.
AB  - DEAD-box RNA helicases, which regulate various processes involving RNA, have two
      RecA-like domains as a catalytic core to alter higher-order RNA structures. We
      determined the 2.2 A resolution structure of the core of the Drosophila DEAD-box
      protein Vasa in complex with a single-stranded RNA and an ATP analog. The ATP
      analog intensively interacts with both of the domains, thereby bringing them into
      the closed form, with many interdomain interactions of conserved residues. The
      bound RNA is sharply bent, avoiding a clash with a conserved alpha helix in the N
      terminal domain. This "wedge" helix should disrupt base pairs by bending one of
      the strands when a duplex is bound. Mutational analyses indicated that the
      interdomain interactions couple ATP hydrolysis to RNA unwinding, probably through
      fine positioning of the duplex relative to the wedge helix. This mechanism, which
      differs from those for canonical translocating helicases, may enable the targeted
      modulation of intricate RNA structures.

PMID- 16630818
TI  - Control of developmental regulators by Polycomb in human embryonic stem cells.
AB  - Polycomb group proteins are essential for early development in metazoans, but
      their contributions to human development are not well understood. We have mapped
      the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire
      nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that
      SUZ12 is distributed across large portions of over two hundred genes encoding key
      developmental regulators. These genes are occupied by nucleosomes trimethylated
      at histone H3K27, are transcriptionally repressed, and contain some of the most
      highly conserved noncoding elements in the genome. We found that PRC2 target
      genes are preferentially activated during ES cell differentiation and that the ES
      cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these
      genes. These results indicate that PRC2 occupies a special set of developmental
      genes in ES cells that must be repressed to maintain pluripotency and that are
      poised for activation during ES cell differentiation.

PMID- 16630819
TI  - A bivalent chromatin structure marks key developmental genes in embryonic stem
      cells.
AB  - The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster
      within regions enriched for genes encoding developmentally important
      transcription factors (TFs). This suggests that HCNE-rich regions may contain key
      regulatory controls involved in development. We explored this by examining
      histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich
      loci. We identified a specific modification pattern, termed "bivalent domains,"
      consisting of large regions of H3 lysine 27 methylation harboring smaller regions
      of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes
      expressed at low levels. We propose that bivalent domains silence developmental
      genes in ES cells while keeping them poised for activation. We also found
      striking correspondences between genome sequence and histone methylation in ES
      cells, which become notably weaker in differentiated cells. These results
      highlight the importance of DNA sequence in defining the initial epigenetic
      landscape and suggest a novel chromatin-based mechanism for maintaining
      pluripotency.

PMID- 16630820
TI  - Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct
      association with beta-catenin/Armadillo.
AB  - The Wnt pathway controls cell fates, tissue homeostasis, and cancer. Its
      activation entails the association of beta-catenin with nuclear TCF/LEF proteins
      and results in transcriptional activation of target genes. The mechanism by which
      nuclear beta-catenin controls transcription is largely unknown. Here we
      genetically identify a novel Wnt/Wg pathway component that mediates the
      transcriptional outputs of beta-catenin/Armadillo. We show that Drosophila Hyrax
      and its human ortholog, Parafibromin, components of the Polymerase-Associated
      Factor 1 (PAF1) complex, are required for nuclear transduction of the Wnt/Wg
      signal and bind directly to the C-terminal region of beta-catenin/Armadillo.
      Moreover, we find that the transactivation potential of Parafibromin/Hyrax
      depends on the recruitment of Pygopus to beta-catenin/Armadillo. Our results
      assign to the tumor suppressor Parafibromin an unexpected role in Wnt signaling
      and provide a molecular mechanism for Wnt target gene control, in which the
      nuclear Wnt signaling complex directly engages the PAF1 complex, thereby
      controlling transcriptional initiation and elongation by RNA Polymerase II.

PMID- 16630821
TI  - The ihog cell-surface proteins bind Hedgehog and mediate pathway activation.
AB  - The ihog gene (interference hedgehog), identified by RNA interference in
      Drosophila cultured cells, encodes a type 1 membrane protein shown here to bind
      and to mediate response to the active Hedgehog (Hh) protein signal. ihog
      mutations produce defects characteristic of Hh signaling loss in embryos and
      imaginal discs, and epistasis analysis places ihog action at or upstream of the
      negatively acting receptor component, Patched (Ptc). The first of two
      extracellular fibronectin type III (FNIII) domains of the Ihog protein mediates a
      specific interaction with Hh protein in vitro, but the second FNIII domain is
      additionally required for in vivo signaling activity and for Ihog-enhanced
      binding of Hh protein to cells coexpressing Ptc. Other members of the Ihog
      family, including Drosophila Boi and mammalian CDO and BOC, also interact with Hh
      ligands via a specific FNIII domain, thus identifying an evolutionarily conserved
      family of membrane proteins that function in Hh signal response.

PMID- 16630822
TI  - Alpha3Na+/K+-ATPase is a neuronal receptor for agrin.
AB  - Agrin, through its interaction with the receptor tyrosine kinase MuSK, mediates
      accumulation of acetylcholine receptors (AChR) at the developing neuromuscular
      junction. Agrin has also been implicated in several functions in brain. However,
      the mechanism by which agrin exerts its effects in neural tissue is unknown. Here
      we present biochemical evidence that agrin binds to the alpha3 subunit of the
      Na+/K+-ATPase (NKA) in CNS neurons. Colocalization with agrin binding sites at
      synapses supports the hypothesis that the alpha3NKA is a neuronal agrin receptor.
      Agrin inhibition of alpha3NKA activity results in membrane depolarization and
      increased action potential frequency in cortical neurons in culture and acute
      slice. An agrin fragment that acts as a competitive antagonist depresses action
      potential frequency, showing that endogenous agrin regulates native alpha3NKA
      function. These data demonstrate that, through its interaction with the
      alpha3NKA, agrin regulates activity-dependent processes in neurons, providing a
      molecular framework for agrin action in the CNS.

PMID- 16630823
TI  - KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1
      enzymatic activity.
AB  - In brain development, apoptosis is a physiological process that controls the
      final numbers of neurons. Here, we report that the activity-dependent prevention
      of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4
      (KIF4), a microtubule-based molecular motor. The C-terminal domain of KIF4 is a
      module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a
      nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as
      a transcriptional regulator. When neurons are stimulated by membrane
      depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4
      from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron
      survival. After dissociation from PARP-1, KIF4 enters into the cytoplasm from the
      nucleus and moves to the distal part of neurites in a microtubule-dependent
      manner. We suggested that KIF4 controls the activity-dependent survival of
      postmitotic neurons by regulating PARP-1 activity in brain development.

PMID- 16630824
TI  - A hybrid vector for ligand-directed tumor targeting and molecular imaging.
AB  - Merging tumor targeting and molecular-genetic imaging into an integrated platform
      is limited by lack of strategies to enable systemic yet ligand-directed delivery
      and imaging of specific transgenes. Many eukaryotic viruses serve for transgene
      delivery but require elimination of native tropism for mammalian cells; in
      contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but
      are otherwise poor vehicles. Here we introduce a system containing cis-elements
      from adeno-associated virus (AAV) and single-stranded bacteriophage. Our
      AAV/phage (AAVP) prototype targets an integrin. We show that AAVP provides
      superior tumor transduction over phage and that incorporation of inverted
      terminal repeats is associated with improved fate of the delivered transgene.
      Moreover, we show that the temporal dynamics and spatial heterogeneity of gene
      expression mediated by targeted AAVP can be monitored by positron emission
      tomography. This new class of targeted hybrid viral particles will enable a wide
      range of applications in biology and medicine.

PMID- 16630825
TI  - Shades of Dejerine--forging a causal link between the visual word form area and
      reading.
AB  - In 1892, the French neurologist Jules Dejerine suggested that pure alexia
      resulted from an occipital lesion that selectively disconnected visual input from
      a region of the brain that housed "optical images of words." In this issue of
      Neuron, Gaillard and colleagues offer evidence consistent with Dejerine's
      proposal and provide new insights to the functional role of the "visual word form
      area."

PMID- 16630826
TI  - Nob mice wave goodbye to eye-specific segregation.
AB  - Spontaneous retinal activity is necessary to establish and maintain eye-specific
      projections to the LGN, but whether the spatial and temporal structure of this
      activity is important remains unclear. A new study by Demas et al. in the current
      issue of Neuron shows that when the frequency of spontaneous retinal waves is
      increased and waves abnormally persist past eye opening, eye-specific projections
      to the LGN desegregate. These results provide important new insight into the
      mechanisms that drive eye-specific refinement and stabilization.

PMID- 16630827
TI  - Numbing the senses: role of TRPA1 in mechanical and cold sensation.
AB  - In this issue of Neuron, Kwan et al. demonstrate that TRPA1 is critical for the
      transduction of noxious cold and mechanical stimuli, as well as in mediating the
      activation of nociceptors by endogenous and natural irritants. Differences
      between the present report and a previous study indicate that further study is
      needed to reach a consensus on the role of TRPA1 in the transduction of
      mechanical and noxious cold stimuli.

PMID- 16630828
TI  - Dendritic enlightenment: using patterned two-photon uncaging to reveal the
      secrets of the brain's smallest dendrites.
AB  - It has been a longstanding challenge for experimentalists to manipulate precisely
      the spatial and temporal patterns of synaptic input to the dendritic tree in
      order to mimic activity occurring in the intact brain and determine their
      importance for synaptic integration. In this issue of Neuron, Losonczy and Magee
      have used rapid multisite two-photon uncaging of glutamate to define patterns of
      synaptic input on a submillisecond and micron scale to investigate the rules for
      summation of synaptic inputs in the fine oblique dendrites of pyramidal neurons.

PMID- 16630829
TI  - Inducible and cell-type restricted manipulation in the entorhinal cortex.
AB  - The entorhinal cortex functions as the gateway to the hippocampal formation.
      However, its role in formation and consolidation of hippocampus-dependent memory
      remains relatively unexplored. In this issue of Neuron, Yasuda and Mayford report
      an elegant cell-type restricted inducible transgenic mouse overexpressing a
      mutant form of CaM kinase II selectively in superficial layers of medial
      entorhinal cortex and its upstream regions. These animals display a selective
      spatial memory deficit during the immediate posttraining period as well as during
      acquisition in the Morris water maze. Similar to the hippocampus, this time
      limited involvement of entorhinal cortex in spatial memory processing suggests a
      crucial role for hippocampal-entorhinal circuitry in spatial memory formation.

PMID- 16630830
TI  - Off on a tangent: thalamocortical axons traverse a permissive corridor across the
      basal telencephalon.
AB  - The forebrain is one of most complex cellular structures known. Two phenomena
      that enable this complexity are tangential migrations that mix neurons from
      distinct progenitor fields, and axon guidance across intervening, noninnervated
      fields. A new paper in Cell by Lopez-Bendito et al. has discovered the
      convergence of these phenomena in the critical thalamocortical system.

PMID- 16630831
TI  - Envisioning the reward.
AB  - The primary visual cortex (area V1) is for vision. At least, that is what most
      researchers believe. However, in a recent issue of Science, Shuler and Bear
      demonstrate a correlate of reward timing in area V1. This surprising result
      indicates that brain circuits for reward processing are more extensive than
      expected and that area V1 has more functionality than previously thought.

PMID- 16630832
TI  - Direct intracranial, FMRI, and lesion evidence for the causal role of left
      inferotemporal cortex in reading.
AB  - Models of the "visual word form system" postulate that a left occipitotemporal
      region implements the automatic visual word recognition required for efficient
      reading. This theory was assessed in a patient in whom reading was explored with
      behavioral measures, fMRI, and intracranial local field potentials. Prior to
      surgery, when reading was normal, fMRI revealed a normal mosaic of ventral visual
      selectivity for words, faces, houses, and tools. Intracranial recordings
      demonstrated that the left occipitotemporal cortex responded with a short latency
      to conscious but also to subliminal words. Surgery removed a small portion of
      word-responsive occipitotemporal cortex overlapping with the word-specific fMRI
      activation. The patient developed a marked reading deficit, while recognition of
      other visual categories remained intact. Furthermore, in the post-surgery fMRI
      map of visual cortex, only word-specific activations disappeared. Altogether,
      these results provide direct evidence for the causal role of the left
      occipitotemporal cortex in the recognition of visual words.

PMID- 16630833
TI  - Assembly of the brainstem cochlear nuclear complex is revealed by intersectional
      and subtractive genetic fate maps.
AB  - The cochlear nuclear complex (CN) is the entry point for central auditory
      processing. Although constituent neurons have been studied physiologically, their
      embryological origins and molecular profiles remain obscure. Applying
      intersectional and subtractive genetic fate mapping approaches, we show that this
      complex develops modularly from genetically separable progenitor populations
      arrayed as rostrocaudal microdomains within and outside the hindbrain (lower)
      rhombic lip (LRL). The dorsal CN subdivision, structurally and topographically
      similar to the cerebellum, arises from microdomains unexpectedly caudal and
      noncontiguous to cerebellar primordium; ventral CN subdivisions arise from more
      rostral LRL. Magnocellular regions receive contributions from LRL and coaxial non
      lip progenitors; contrastingly, ensheathing granule cells derive principally from
      LRL. Also LRL-derived and molecularly similar to CN granule cells are
      precerebellar mossy fiber neurons; surprisingly, these ostensibly intertwined
      populations have separable origins and adjacent but segregated migratory streams.
      Together, these findings provide new platforms for investigating the development
      and evolution of auditory and cerebellar systems.

PMID- 16630834
TI  - Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary for NRIF
      nuclear translocation and apoptosis in sympathetic neurons.
AB  - The p75 neurotrophin receptor regulates neuronal survival, promoting it in some
      contexts yet activating apoptosis in others. The mechanism by which the receptor
      elicits these differential effects is poorly understood. Here, we demonstrate
      that p75 is cleaved by gamma-secretase in sympathetic neurons, specifically in
      response to proapoptotic ligands. This cleavage resulted in ubiquitination and
      subsequent nuclear translocation of NRIF, a DNA binding protein essential for p75
      mediated apoptosis. Inhibition of gamma-secretase or expression of a mutant p75
      resistant to this protease prevented receptor proteolysis, blocked NRIF nuclear
      entry, and prevented apoptosis. In contrast, overexpression of the p75 ICD
      resulted in NRIF nuclear accumulation and apoptosis. The receptor proteolysis and
      NRIF nuclear localization were also observed in vivo during naturally occurring
      cell death in the superior cervical ganglia. These results indicate that p75
      mediated apoptosis requires gamma-secretase dependent release of its ICD, which
      facilitates nuclear translocation of NRIF.

PMID- 16630835
TI  - SALM synaptic cell adhesion-like molecules regulate the differentiation of
      excitatory synapses.
AB  - Synaptic cell adhesion molecules (CAMs) are known to play key roles in various
      aspects of synaptic structures and functions, including early differentiation,
      maintenance, and plasticity. We herein report the identification of a family of
      cell adhesion-like molecules termed SALM that interacts with the abundant
      postsynaptic density (PSD) protein PSD-95. SALM2, a SALM isoform, distributes to
      excitatory, but not inhibitory, synaptic sites. Overexpression of SALM2 increases
      the number of excitatory synapses and dendritic spines. Mislocalized expression
      of SALM2 disrupts excitatory synapses and dendritic spines. Bead-induced direct
      aggregation of SALM2 results in coclustering of PSD-95 and other postsynaptic
      proteins, including GKAP and AMPA receptors. Knockdown of SALM2 by RNA
      interference reduces the number of excitatory synapses and dendritic spines and
      the frequency, but not amplitude, of miniature excitatory postsynaptic currents.
      These results suggest that SALM2 is an important regulator of the differentiation
      of excitatory synapses.

PMID- 16630836
TI  - Failure to maintain eye-specific segregation in nob, a mutant with abnormally
      patterned retinal activity.
AB  - Axon terminals from the two eyes initially overlap in the dorsal-lateral
      geniculate nucleus (dLGN) but subsequently refine to occupy nonoverlapping
      territories. Retinal activity is required to establish and maintain this
      segregation. We show that despite the presence of retinal activity, segregated
      projections desegregate when the structure of activity is altered. Early in
      development, spontaneous retinal activity in the no b-wave (nob) mouse is
      indistinguishable from that of wild-type mice, and eye-specific segregation
      proceeds normally. But, around eye-opening, spontaneous and visually evoked
      activity in nob retinas become abnormal, coincident with a failure to preserve
      precise eye-specific territories. Dark-rearing studies suggest that altered
      visual experience is not responsible. Transgenic rescue of the mutated protein
      (nyctalopin) within nob retinal interneurons, without rescuing expression in
      either retinal projection neurons or their postsynaptic targets in the dLGN,
      restores spontaneous retinal activity patterns and prevents desegregation. Thus,
      normally structured spontaneous retinal activity stabilizes newly refined
      retinogeniculate circuitry.

PMID- 16630837
TI  - SAD: a presynaptic kinase associated with synaptic vesicles and the active zone
      cytomatrix that regulates neurotransmitter release.
AB  - A serine/threonine kinase SAD-1 in C. elegans regulates synapse development. We
      report here the isolation and characterization of mammalian orthologs of SAD-1,
      named SAD-A and SAD-B, which are specifically expressed in the brain. SAD-B is
      associated with synaptic vesicles and, like the active zone proteins CAST and
      Bassoon, is tightly associated with the presynaptic cytomatrix in nerve
      terminals. A short conserved region (SCR) in the COOH-terminus is required for
      the synaptic localization of SAD-B. Overexpression of SAD-B in cultured rat
      hippocampal neurons significantly increases the frequency of miniature excitatory
      postsynaptic current but not its amplitude. Introduction of SCR into presynaptic
      superior cervical ganglion neurons in culture significantly inhibits evoked
      synaptic transmission. Moreover, SCR decreases the size of the readily releasable
      pool measured by applying hypertonic sucrose. Furthermore, SAD-B phosphorylates
      the active zone protein RIM1 but not Munc13-1. These results suggest that
      mammalian SAD kinase presynaptically regulates neurotransmitter release.

PMID- 16630838
TI  - TRPA1 contributes to cold, mechanical, and chemical nociception but is not
      essential for hair-cell transduction.
AB  - TRPA1, a member of the transient receptor potential (TRP) family of ion channels,
      is expressed by dorsal root ganglion neurons and by cells of the inner ear, where
      it has proposed roles in sensing sound, painful cold, and irritating chemicals.
      To test the in vivo roles of TRPA1, we generated a mouse in which the essential
      exons required for proper function of the Trpa1 gene were deleted. Knockout mice
      display behavioral deficits in response to mustard oil, to cold ( approximately 0
      degrees C), and to punctate mechanical stimuli. These mice have a normal startle
      reflex to loud noise, a normal sense of balance, a normal auditory brainstem
      response, and normal transduction currents in vestibular hair cells. TRPA1 is
      apparently not essential for hair-cell transduction but contributes to the
      transduction of mechanical, cold, and chemical stimuli in nociceptor sensory
      neurons.

PMID- 16630839
TI  - Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal
      neurons.
AB  - Although radial oblique dendrites are a major synaptic input site in CA1
      pyramidal neurons, little is known about their integrative properties. We have
      used multisite two-photon glutamate uncaging to deliver different spatiotemporal
      input patterns to single branches while simultaneously recording the uncaging
      evoked excitatory postsynaptic potentials and local Ca2+ signals. Asynchronous
      input patterns sum linearly in spite of the spatial clustering and produce Ca2+
      signals that are mediated by NMDA receptors (NMDARs). Appropriately timed and
      sized input patterns ( approximately 20 inputs within approximately 6 ms) produce
      a supralinear summation due to the initiation of a dendritic spike. The Ca2+
      signals associated with synchronous input were larger and mediated by influx
      through both NMDARs and voltage-gated Ca2+ channels (VGCCs). The oblique spike is
      a fast Na+ spike whose duration is shaped by the coincident activation of NMDAR,
      VGCCs, and transient K+ currents. Our results suggest that individual branches
      can function as single integrative compartments.

PMID- 16630840
TI  - CaMKII activation in the entorhinal cortex disrupts previously encoded spatial
      memory.
AB  - To investigate the role of the entorhinal cortex in memory at a molecular level,
      we developed transgenic mice in which transgene expression was inducible and
      limited to the superficial layers of the medial entorhinal cortex, pre- and
      parasubiculum. We found that expression of a constitutively active mutant form of
      CaMKII in these structures disrupted spatial memory formation. Immediate post
      training activation of the transgene disrupted previously established memory
      while transgene activation 3 weeks following the training was ineffective. These
      results demonstrate that, similar to the hippocampus, the entorhinal cortex plays
      a time-limited role in spatial memory formation but is not a final cortical
      repository of long-term memory. Moreover, these results suggest that the
      indiscriminate activation of CaMKII is able to disrupt preexisting memories,
      possibly by altering the pattern of synaptic weight changes that are thought to
      form the basis of the memory trace.

PMID- 16630841
TI  - The parvocellular LGN provides a robust disynaptic input to the visual motion
      area MT.
AB  - Dorsal visual cortical areas are thought to be dominated by input from the
      magnocellular (M) visual pathway, with little or no parvocellular (P)
      contribution. These relationships are supported by a close correlation between
      the functional properties of these areas and the M pathway and by a lack of
      anatomical evidence for P input. Here we use rabies virus as a retrograde
      transynaptic tracer to show that the dorsal area MT receives strong input, via a
      single relay, from both M and P cells of the lateral geniculate nucleus. This
      surprising P input, likely relayed via layer 6 Meynert cells in primary visual
      cortex, can provide MT with sensitivity to a more complete range of spatial,
      temporal, and chromatic cues than the M pathway alone. These observations provide
      definitive evidence for P pathway input to MT and show that convergence of
      parallel visual pathways occurs in the dorsal stream.

PMID- 16630842
TI  - When the brain loses its self: prefrontal inactivation during sensorimotor
      processing.
AB  - A common theme in theories of subjective awareness poses a self-related
      "observer" function, or a homunculus, as a critical element without which
      awareness can not emerge. Here, we examined this question using fMRI. In our
      study, we compared brain activity patterns produced by a demanding sensory
      categorization paradigm to those engaged during self-reflective introspection,
      using similar sensory stimuli. Our results show a complete segregation between
      the two patterns of activity. Furthermore, regions that showed enhanced activity
      during introspection underwent a robust inhibition during the demanding
      perceptual task. The results support the notion that self-related processes are
      not necessarily engaged during sensory perception and can be actually suppressed.

PMID- 16630882
TI  - XPB: An essential helicase involved in both transcription and repair of DNA.
AB  - Helicases are molecular motors known to unwind double-stranded DNA. In a recent
      issue of Molecular Cell, Fan et al. (2006) revealed the core structure of XPB
      helicase, a component of transcription factor IIH, and proposed a mechanism for
      its dual role in transcription and nucleotide excision repair.

PMID- 16630883
TI  - Reversible monoubiquitination of PCNA: A novel slant on regulating translesion
      DNA synthesis.
AB  - Deubiquitination of monoubiquitinated proteins is effected by a large number of
      deubiquitinating enzymes (DUBs) that function as cysteine proteases in eukaryotic
      cells. Huang et al. (2006) report the regulation of monoubiquitination of PCNA by
      autocleavage of a DUB called USP1 in cells exposed to UV radiation.

PMID- 16630884
TI  - Beating the heat: A translation factor and an RNA mobilize the heat shock
      transcription factor HSF1.
AB  - Cells respond to stress via orchestrated modifications in gene expression; in a
      recent publication in Nature, Shamovsky et al. (2006) report that an RNA and a
      translation factor regulate the activity of a transcriptional activator essential
      to the mammalian heat shock response.

PMID- 16630885
TI  - Two-step selection of mRNAs in initiation of protein synthesis.
AB  - In a recent issue of Molecular Cell, Studer and Joseph (2006) clarified the
      molecular basis of the "standby model" and demonstrated how two-step binding of
      mRNAs to the small ribosomal subunit depends on initiator tRNA and initiation
      factors, with far-reaching implications for posttranscriptional regulation of
      gene expression.

PMID- 16630886
TI  - Climbing the Greatwall to mitosis.
AB  - Greatwall kinase is a conserved regulator of mitotic entry, and new work in
      Xenopus egg extracts (Yu et al., 2006) shows that Greatwall is required for the
      positive feedback loop that removes inhibitory tyrosine phosphate from the
      central mitotic regulatory kinase Cdc2.

PMID- 16630887
TI  - Genome-wide occupancy profile of mediator and the Srb8-11 module reveals
      interactions with coding regions.
AB  - Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC
      subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits
      and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use
      chromatin immunoprecipitation (ChIP) and DNA microarrays to investigate genome
      wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator
      and the Srb8-11 module display similar binding patterns, and interactions with
      promoters and upstream activating sequences correlate with increased
      transcription activity. Unexpectedly, Mediator also interacts with the downstream
      coding region of many genes. These interactions display a negative bias for
      positions closer to the 5' ends of open reading frames (ORFs) and appear
      functionally important, because downregulation of transcription in a temperature
      sensitive med17 mutant strain correlates with increased Mediator occupancy in the
      coding region. We propose that Mediator coordinates transcription initiation with
      transcriptional events in the coding region of eukaryotic genes.

PMID- 16630888
TI  - Genome-wide location of the coactivator mediator: Binding without activation and
      transient Cdk8 interaction on DNA.
AB  - Mediator is a general coactivator of RNA polymerase II (Pol II) transcription.
      Genomic location analyses of different Mediator subunits indicate a uniformly
      composed core complex upstream of active genes but unexpectedly also upstream of
      inactive genes and on the coding regions of some highly active genes. The
      repressive Cdk8 submodule is associated with core Mediator at all sites but with
      a lower degree of occupancy, indicating transient interaction, regardless of
      promoter activity. This suggests gene-specific regulation of Cdk8 activity,
      rather than regulated Cdk8 recruitment. Mediator presence is not necessarily
      linked to transcription. This goes beyond Cdk8-repressed genes, indicating that
      Mediator can mark some regulatory regions ahead of additional signals. Overlap
      with intergenic Pol II location in stationary phase points to a role as a binding
      platform for inactive Pol II during quiescence. These results shed light on Cdk8
      repression, suggest additional roles for Mediator, and query models of
      recruitment-coupled regulation.

PMID- 16630889
TI  - Proteomic profiling of ClpXP substrates after DNA damage reveals extensive
      instability within SOS regulon.
AB  - ClpXP, a bacterial AAA+ protease, controls intracellular levels of many stress
      response proteins. To investigate substrate profile changes caused by a specific
      environmental stress, quantitative mass spectrometry (SILAC) was used to analyze
      proteins trapped by ClpXP(trap) before and after DNA damage. The abundance of
      half of the trapped proteins changed more than 3-fold after damage.
      Overrepresented substrates included the DNA-repair proteins RecN and UvrA. Among
      SOS-response proteins, 25% were ClpXP substrates and, importantly, nearly all of
      the highly induced regulon members were rapidly degraded. Other proteins,
      including the stress regulator sigma(S), were underrepresented in ClpXP(trap)
      after DNA damage; overproduction experiments suggest that simple substrate
      competition does not account for this reduced recognition. We conclude that
      damage-response proteins are an unusually rapidly degraded family and that ClpXP
      has substantial capacity to process the influx of newly synthesized substrates
      while maintaining the ability to degrade its other substrates in an
      environmentally responsive manner.

PMID- 16630890
TI  - The structure of SOCS3 reveals the basis of the extended SH2 domain function and
      identifies an unstructured insertion that regulates stability.
AB  - SOCS3 is essential for regulating the extent, duration, and specificity of
      cellular responses to cytokines such as G-CSF and IL-6. Here we describe the
      solution structure of SOCS3, the first structure determined for any SOCS protein,
      in complex with a phosphotyrosine-containing peptide from the IL-6 receptor
      signaling subunit gp130. The structure of the complex shows that seven peptide
      residues form a predominantly hydrophobic binding motif. Regions outside the
      SOCS3 SH2 domain are important for ligand binding, in particular, a single 15
      residue alpha helix immediately N-terminal to the SH2 domain makes direct
      contacts with the phosphotyrosine binding loop and, in part, determines its
      geometry. The SH2 domain itself is remarkable in that it contains a 35 residue
      unstructured PEST motif insertion that is not required for STAT inhibition. The
      PEST motif increases SOCS3 turnover and affects its degradation pathway, implying
      that it has an important regulatory role inside the cell.

PMID- 16630891
TI  - A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1
      functions as an M-Ras effector to modulate Raf activity.
AB  - Ras family GTPases (RFGs) are known to share many regulatory and effector
      proteins. How signaling and biological specificity is achieved is poorly
      understood. Using a proteomics approach, we have identified a complex comprised
      of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a
      highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf
      activity by dephosphorylating the S259 inhibitory site of Raf proteins bound to
      other molecules of M-Ras or Ras. Therefore, distinct RFGs, through independent
      effectors, can regulate different steps in the activation of Raf kinases. Shoc2
      function is essential for activation of the MAPK pathway by growth factors.
      Furthermore, in tumor cells with Ras gene mutations, inhibition of Shoc2
      expression inhibits MAPK, but not PI3K activity. We propose that the Shoc2-PP1c
      holoenzyme provides an attractive therapeutic target for inhibition of the MAPK
      pathway in cancer.

PMID- 16630892
TI  - Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch
      regulating its transcriptional activity in vivo.
AB  - SATB1 regulates gene expression by acting as a "docking site" for several
      chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or
      coactivators (HATs) directly to promoters. However, how these contrasting
      effectors act at the level of SATB1 is not clear. We show here that
      phosphorylation by PKC acts as a switch to determine whether SATB1 interacts with
      HDAC1 or PCAF. Phosphorylation and dephosphorylation of SATB1 exerted opposing
      effects on MAR-linked reporter activity in vivo. SATB1 interacted with both
      CBP/p300 and PCAF HATs; however, these interactions resulted in the acetylation
      of the PDZ-like domain of SATB1 by PCAF but not by CBP/p300 and resulted in loss
      of its DNA binding activity. Using the T cell activation model, we provide
      mechanistic insights into how IL-2 transcription is reciprocally governed by the
      phosphorylation status of SATB1 and propose that a similar mechanism may dictate
      the ability of SATB1 to function as a global regulator.

PMID- 16630893
TI  - Caspase-9 holoenzyme is a specific and optimal procaspase-3 processing machine.
AB  - Caspase-9 activation is critical for intrinsic cell death. The activity of
      caspase-9 is increased dramatically upon association with the apoptosome, and the
      apoptosome bound caspase-9 is the caspase-9 holoenzyme (C9Holo). In this study,
      we use quantitative enzymatic assays to fully characterize C9Holo and a leucine
      zipper-linked dimeric caspase-9 (LZ-C9). We surprisingly show that LZ-C9 is more
      active than C9Holo for the optimal caspase-9 peptide substrate LEHD-AFC but is
      much less active than C9Holo for the physiological substrate procaspase-3. The
      measured Km values of C9Holo and LZ-C9 for LEHD-AFC are similar, demonstrating
      that dimerization is sufficient for catalytic activation of caspase-9. The lower
      activity of C9Holo against LEHD-AFC may be attributed to incomplete C9Holo
      assembly. However, the measured Km of C9Holo for procaspase-3 is much lower than
      that of LZ-C9. Therefore, in addition to dimerization, the apoptosome activates
      caspase-9 by enhancing its affinity for procaspase-3, which is important for
      procaspase-3 activation at the physiological concentration.

PMID- 16630894
TI  - The apoptosome activates caspase-9 by dimerization.
AB  - The apical protease of the human intrinsic apoptotic pathway, caspase-9, is
      activated in a polymeric activation platform known as the apoptosome. The
      mechanism has been debated, and two contrasting hypotheses have been suggested.
      One of these postulates an allosteric activation of monomeric caspase-9; the
      other postulates a dimer-driven assembly at the surface of the apoptosome--the
      "induced proximity" model. We show that both Hofmeister salts and a reconstituted
      mini-apoptosome activate caspase-9 by a second-order process, compatible with a
      conserved dimer-driven process. Significantly, replacement of the recruitment
      domain of the apical caspase of the extrinsic apoptotic pathway, caspase-8, by
      that of caspase-9 allows activation of this hybrid caspase by the apoptosome.
      Consequently, apical caspases can be activated simply by directing their zymogens
      to the apoptosome, ruling out the requirement for allosteric activation and
      supporting an induced proximity dimerization model for apical caspase activation
      in vivo.

PMID- 16630895
TI  - Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by
      lipoprotein receptors.
AB  - Proteins of the low-density lipoprotein receptor (LDLR) family are remarkable in
      their ability to bind an extremely diverse range of protein and lipoprotein
      ligands, yet the basis for ligand recognition is poorly understood. Here, we
      report the 1.26 A X-ray structure of a complex between a two-module region of the
      ligand binding domain of the LDLR and the third domain of RAP, an escort protein
      for LDLR family members. The RAP domain forms a three-helix bundle with two
      docking sites, one for each LDLR module. The mode of recognition at each site is
      virtually identical: three conserved, calcium-coordinating acidic residues from
      each LDLR module encircle a lysine side chain protruding from the second helix of
      RAP. This metal-dependent mode of electrostatic recognition, together with
      avidity effects resulting from the use of multiple sites, represents a general
      binding strategy likely to apply in the binding of other basic ligands to LDLR
      family proteins.

PMID- 16630896
TI  - A wiring of the human nucleolus.
AB  - Recent proteomic efforts have created an extensive inventory of the human
      nucleolar proteome. However, approximately 30% of the identified proteins lack
      functional annotation. We present an approach of assigning function to
      uncharacterized nucleolar proteins by data integration coupled to a machine
      learning method. By assembling protein complexes, we present a first draft of the
      human ribosome biogenesis pathway encompassing 74 proteins and hereby assign
      function to 49 previously uncharacterized proteins. Moreover, the functional
      diversity of the nucleolus is underlined by the identification of a number of
      protein complexes with functions beyond ribosome biogenesis. Finally, we were
      able to obtain experimental evidence of nucleolar localization of 11 proteins,
      which were predicted by our platform to be associates of nucleolar complexes. We
      believe other biological organelles or systems could be "wired" in a similar
      fashion, integrating different types of data with high-throughput proteomics,
      followed by a detailed biological analysis and experimental validation.

PMID- 16630899
TI  - Impact of stereotactic hematoma evacuation on medical costs during the chronic
      period in patients with spontaneous putaminal hemorrhage: a randomized study.
AB  - OBJECTIVE: Stereotactic hematoma evacuation (SHE) has been reported to reduce
      mortality and to improve functional outcome in patients with spontaneous
      putaminal hemorrhage. Stereotactic hematoma evacuation has not been widely
      accepted, however, as a standard therapy because its effect on functional outcome
      has been regarded as marginal and insufficient to justify the costs of surgery.
      We reassessed the value of SHE by analyzing its impact on chronic-period medical
      costs based on an original randomized study carried out by us. METHODS: In total,
      490 patients were entered into the study. The degree of neurologic severity was
      defined on admission according to the neurologic grades (NGs) ranging from NG1 to
      NG5, adopted by the Japanese Cooperative Study on Stroke Surgery. The NG2 and 3
      patients were randomized into 2 groups with different treatment protocols (group
      I, SHE; group II, conservative treatment). On the other hand, the NG1, 4, and 5
      patients were excluded from the randomization because a large-scale retrospective
      study in Japan had revealed that surgical treatment in patients assigned to these
      NG grades does not improve functional outcome. Among the 490 patients, 248 were
      excluded and 242 were randomized strictly. The latter patients comprised 148 men
      and 94 women. Their ages ranged from 38 to 80 years (mean, 60.5 years). The
      medical costs for patient care were analyzed at 1 year after onset. RESULTS: As
      compared with group II, group I demonstrated a lower mortality and better
      recovery to functional independence in NG3 patients. As compared with group II,
      group I revealed lower costs at 1 year after hemorrhage in NG2 patients, probably
      reflecting reduced neurologic deficits brought about by the SHE, and
      approximately the same costs in NG3 patients. CONCLUSION: Stereotactic hematoma
      evacuation is clearly of value from the medicoeconomical point of view in
      selected patients with spontaneous putuminal hemorrhage, whose eyes are closed
      but open to weak stimuli (NG2) or strong stimuli (NG3) on admission.

PMID- 16630901
TI  - Surgical approaches to the atrium of the lateral ventricle: microsurgical
      anatomy.
AB  - BACKGROUND: Managing lesions situated in the atrium of the lateral ventricle
      remains a challenging neurosurgical problem. The purposes of this study were to
      examine the microsurgical anatomy of the atrium of the lateral ventricle and the
      optic radiation and to define the differences in the exposure obtained by various
      surgical approaches. METHODS: Fifteen adult cadaveric specimens were studied
      using magnification x3 to x40 after perfusion of the arteries and veins with
      colored silicone. The microsurgical anatomy of the atrium of the lateral
      ventricle was examined. The relationship between the optic radiation and the
      atrium was studied using the white matter fiber dissection technique. Surgical
      approaches to the atrium of the lateral ventricle were examined in stepwise
      dissection. RESULTS: The medial and inferior walls of the atrium were free from
      optic radiation fibers. Surgical approaches to the atrium of the lateral
      ventricle are divided into 3 routes: (1) anterior approach: transsylvian
      approach, (2) posterior approaches: posterior transcortical, posterior
      transcallosal, occipital, and supracerebellar transtentorial approaches, and (3)
      lateral approaches: transtemporal and subtemporal approaches. CONCLUSION:
      Knowledge of the microsurgical anatomy of the atrium of the lateral ventricle and
      surrounding vital structures and the choice of an appropriate surgical approach
      will help surgeons perform safe and minimally invasive surgery.

PMID- 16630902
TI  - Effects of anterior contralateral cervical microdiskectomy on radiological and
      clinical outcome.
AB  - BACKGROUND: We have conducted a prospective study to investigate the relationship
      between cervical spine alignment and clinical outcome in 102 patients undergoing
      anterior contralateral microdiskectomy without interbody graft or cage. METHODS:
      Preoperative and postoperative lateral cervical radiographs were obtained, and
      curvature of the surgically treated spinal segments and the overall curvature of
      the cervical spine were evaluated in all patients. Clinical outcomes were
      assessed using the NDI and SF-36. RESULTS: There was no significant change in the
      mean overall cervical curvature (C2-C7) angles postoperatively in late follow-up
      findings (P = .72). It represented a statistically significant mean loss of 2.73
      degrees of segmental lordosis (P < .0001). The NDI scores decreased significantly
      in both early and late follow-up evaluations, and the SF-36 scores demonstrated
      significant improvement in late follow-up results in our series. Analysis of
      clinical outcome showed no statistical differences between patients with
      segmental lordosis or kyphosis. CONCLUSION: Despite the kyphosis seen at the
      treated levels, the overall alignment between C2 and C7 did not change
      significantly, indicating that the untreated segments of the cervical spine were
      compensating for focal kyphosis.

PMID- 16630904
TI  - A perspective for the selection of surgical approaches in patients with upper
      thoracic and cervicothoracic junction instabilities.
AB  - OBJECTIVE: To reach the upper thoracic vertebrae, a number of extensive
      approaches have been proposed. The purpose of this study is to provide a clear
      perspective for the selection of surgical approaches in patients who undergo
      vertebral body resection, reconstruction, and stabilization for upper thoracic
      and cervicothoracic junction instabilities. METHODS: Seventeen patients with
      upper thoracic or cervicothoracic junction (C7-T6) instability underwent surgery
      between January 1999 and May 2004. All patients presented with pain and/or
      neurological deficits. The causes of instabilities were 10 traumas and 7
      pathological fractures. The approach chosen was primarily dictated by 3 factors
      including (1) type of injury, (2) level of lesion, and (3) time of admission.
      Ventral surgical approach was performed to all pathological and traumatic
      fractures causing anterior spinal cord compression. Level of lesion determined
      the selection of the type of ventral surgical approach, namely, supramanubrial,
      transmanubrial, or lateral transthoracic. On the other hand, combined (anterior
      and posterior) approach was performed to all late admitted trauma patients.
      RESULTS: Twelve anterior, 2 combined (anterior and posterior), and 3 posterior
      approaches were performed in this study. Anterior approaches included 3
      transmanubrial, 5 upper lateral transthoracic, and 4 supramanubrial cervical
      dissection procedures for decompression, fusion, and plate-screw fixation
      depending on the levels of the lesion. The mean follow-up period was 18 months,
      ranging from 10 to 58 months. Nonunion or instrument-related complications were
      not observed. The postoperative neurological conditions were statistically
      significantly better than the preoperative ones (P = .003). CONCLUSION:
      Consideration of the type of injury, level of lesion, and time of admission can
      provide a perspective for the selection of side of surgical approach for this
      transitional part of the spinal column. This study also suggests that
      supramanubrial cervical approach achieves sufficient exposure up to T2,
      transmanubrial approach for T3, and lateral transthoracic approach below T3.

PMID- 16630906
TI  - Efficacy and safety of the use of titanium mesh cages and anterior cervical
      plates for interbody fusion after anterior cervical corpectomy.
AB  - BACKGROUND: To determine the safety and effectiveness of the use of titanium mesh
      cages (TMCs) and anterior cervical plates (ACPs) for interbody fusion after
      anterior cervical corpectomy. METHODS: From June 2001 to June 2003, 15 patients
      underwent reconstruction with TMCs and ACPs for interbody fusion after anterior
      cervical corpectomy in our hospital. The mean follow-up is 13.6 months (range, 9
      24 months). Subjects included those with cervical degenerative, traumatic, or
      pathological diseases. Titanium mesh cages were filled with autologous bone
      grafts taken from the corpectomy and iliac crest bone chips and were all filled
      with triosite (calcium phosphate ceramics). The patients' observable signs,
      neurological reconstruction results, and complications were fully and explicitly
      recorded throughout the procedure. Radiological imaging studies for measurements
      of coronal and sagittal angles, sagittal displacements, and settling ratio
      changes were performed to evaluate spinal stability. We used axial cervical
      computed tomography (CT) and reconstructive sagittal cervical CT to demonstrate
      interbody fusion within titanium mesh. RESULTS: The alleviation and frequent
      disappearance of the subjects' original symptoms and the significant neurological
      recovery obvious in most patients indicated that postoperative spinal stability
      could be well maintained. No significant differences in mean cage height-related
      settling rates, mean sagittal displacements, and mean coronal and sagittal angle
      changes were observed between 1-level and multilevel corpectomy. All patients who
      received axial and reconstructive sagittal cervical CT scan could demonstrate
      true interbody fusion within TMC, and no nonunions were present. Cage
      malplacement was observed in one subject who had neck pain and neck stiffness,
      rather than from radiculopathy or myelopathy. One subject died of acute
      myocardial infarction. There were no ceramic-related complications. CONCLUSIONS:
      Based on preliminary findings from this study, reconstruction involving TMC
      interbody fusion with ACP fixation after anterior cervical corpectomy serves as
      an effective and safe method for the treatment of cervical disease.

PMID- 16630907
TI  - Patterns of neuroaxis dissemination of gliomas: suggestion of a classification
      based on magnetic resonance imaging findings.
AB  - BACKGROUND: Local invasion is the hallmark of malignant glioma dissemination.
      Leptomeningeal dissemination, a serious complication of malignant gliomas, has
      been increasingly observed. To correlate the physiopathologic mechanisms and the
      magnetic resonance imaging patterns of neuroaxis dissemination, a classification
      of malignant glioma dissemination is proposed (Instituto de Neurologia de
      Curitiba Classification). METHODS: This classification includes the following
      patterns of dissemination: leptomeningeal (type I), nodular (type Ia), diffuse
      (type Ib); subependymal (type II); satellite (type IIIa, IIIb); and mixed (type
      IV), combination of 2 or more previous types. Of 138 patients with histologically
      confirmed gliomas treated between 2000 and 2004, 10 presented neuroaxis
      dissemination and were evaluated. RESULTS: The distribution of dissemination
      patterns was as follows: subependymal, 4 of 10; diffuse leptomeningeal, 1 of 10;
      nodular leptomeningeal, 1 of 10; and satellite, 4 of 10. Mean interval between
      primary tumor and dissemination was 4 months. The most frequent glioma
      dissemination risk factor was entering the ventricular system during surgery.
      CONCLUSIONS: Improvements in our diagnostic imaging capabilities have contributed
      to a better understanding of the patterns of malignant glioma dissemination.
      Using this information, we present a useful classification scheme, applicable to
      patients with neuroaxis dissemination, which will help standardize future
      discussions aimed at understanding these patterns of tumor spread.

PMID- 16630910
TI  - Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and
      clonogenic death of C6 glioma in vitro.
AB  - BACKGROUND: Radiation therapy after surgical resection is the approved treatment
      of gliomas, and survival benefits are reported with taxane-based chemotherapy. We
      investigated whether these regimes could be augmented with blood-brain barrier
      permeable drugs, N and D. Noscapine is an opioid antitussive, which acts anti
      cancer via blocking microtubule dynamics. Diltiazem is a calcium channel-blocking
      cardiac antiarrythmic, which also blocks tumor growth and P-glycoprotein.
      METHODS: Effects of N (11.1 micromol/L), D (11.1 micromol/L), and T (11.7
      micromol/L) were monitored in C6 glioma cells via S phase, colony formation, and
      fine structure analysis. RESULTS: Taxol depleted S phase from 35.2% to 12.2%.
      Both N and D synergistically augmented T-mediated S-phase depletion, and they
      also effectively reduced colonies, which were more potent by N by 49%. Taxol
      reduced colonies by 98%, and there were almost no surviving colonies in
      copresence of T with either N or D. Colony reduction by radiotherapy was
      increased strongly by T and significantly by N. Taxol and radiation profoundly
      increased number of mitochondria. Both D and N suppressed this increase via
      myelinosis and autophagy. CONCLUSION: Noscapine and D should be further tested in
      animal models because of their potential and already-present clinical
      applicability.

PMID- 16630912
TI  - Intramedullary lipoma of the cervicodorsal spinal cord with intracranial
      extension: case report.
AB  - BACKGROUND: An unusual case of an extensive intramedullary lipoma of the
      cervicodorsal spinal cord with intracranial extension causing compression of
      spinal cord and brainstem is described. CASE DESCRIPTION: A 3-year-old child with
      lack of limb movement since birth, the cause of which had remained obscure,
      developed opisthotonos and episodes of severe respiratory difficulty with brief
      periods of apnea. Craniospinal computed tomography and magnetic resonance imaging
      (MRI) were diagnostic of lipoma. Urgent occipitocervical decompression and
      subtotal removal of the posterior fossa and cervical spinal cord lipoma resulted
      in lasting resolution of symptoms. CONCLUSIONS: Extensive spinal cord lipomas
      with intracranial extension can present with alarming spinal cord/medullary
      compression and respiratory symptoms. Computed tomographic scan and MRI are
      diagnostic. Total removal is not feasible, or necessary, because subtotal removal
      and decompression give long-lasting resolution of symptoms.

PMID- 16630913
TI  - Secondary intracranial neoplasms exhibiting features of astrocytoma and
      neuroblastoma in 2 children treated for acute lymphoblastic leukemia: report of 2
      cases.
AB  - With the advent of more aggressive antineoplastic combination chemotherapies,
      agents with fewer adverse effects, prophylactic central nervous system radiation
      treatments, and more efficacious antibiotics, the number of childhood cancer
      survivors is continually increasing. These patients place a new responsibility on
      clinicians; systematic follow-up with effective intervention is necessary to
      reduce the consequences of the treatments themselves. We report 2 patients who
      were diagnosed with pre-B-cell acute lymphoblastic leukemia and later presented
      with intracranial malignancies. Both patients were treated with radiation and
      with similar chemotherapeutic regimens. Each patient was in remission for
      leukemia at the time of diagnosis of the second malignancy. The possible causes
      of the brain tumors in association with acute lymphoblastic leukemia are
      discussed.

PMID- 16630914
TI  - Posterior interosseous nerve palsy due to intermuscular lipoma.
AB  - Lipomas are usually subcutaneous and asymptomatic. Rarely, they can occur in a
      deeper soft tissue plane exerting pressure on adjacent nerves. When adjacent to
      the neck of the radius, it can cause posterior interosseous nerve compression. In
      this case report, posterior interosseous nerve palsy due to an intermuscular
      lipoma is reported.

PMID- 16630916
TI  - Chiari I malformation accompanied by assimilation of the atlas, Klippel-Feil
      syndrome, and syringomyelia: case report.
AB  - BACKGROUND: Chiari I malformation, accompanied by superposed bony anomaly of the
      craniovertebral junction, is comparatively rare. We report a case of Chiari I
      malformation accompanied by assimilation of the atlas, Klippel-Feil syndrome, and
      syringomyelia. CASE DESCRIPTION: The patient was a 61-year-old woman
      demonstrating numbness of the extremities, sensory impairment, muscular weakness,
      and tendon hyper-reflexia. X-ray images and CT scans demonstrated assimilation of
      the atlas to the occipital bone, C2 and C3 fusion, abnormal passage of the
      vertebral arteries, and an anomalous bony mass on the right lateral mass of the
      atlas protruding into the spinal column. The odontoid process was also deviated
      to the left. Magnetic resonance images demonstrated bilateral descent of the
      cerebellar tonsils and syringomyelia extending from C6 to T8. Computed
      tomographic scans with the head rotated to the right demonstrated increased
      narrowing of the vertebral column caused by the right lateral mass of the atlas,
      and MR images confirmed exaggerated deformation of the spinal cord at the same
      region. This deformation manifested no neurologic symptoms, and we therefore
      performed foramen magnum decompression and duraplasty using Gore-Tex (W.L. Gore &
      Associates, Inc., Flagstaff, AZ). In the early postoperative period, neurologic
      symptoms improved. CONCLUSION: We believe it is important that a treatment plan
      for Chiari I malformation accompanied by bony anomaly of the craniovertebral
      junction be determined based on morphologic investigation of the region
      supplemented by dynamic imaging-based evaluation of instability, or a careful
      inspection for atypical passage of the vertebral arteries, a frequent site of
      complication.

PMID- 16630918
TI  - Compound elevated skull fracture: a forgotten type of skull fracture.
AB  - BACKGROUND AND OBJECTIVE: We report 4 patients who presented with a rare type of
      vault fracture. This form of fracture has only been described in few instances in
      the literature. CASE DESCRIPTION: All the patients presented with elevation of
      free skull fracture fragments. The etiologies were assault (1 patient), domestic
      accident (1 patient), and road traffic accident (2 patients). All the fractures
      were compound as in previously reported cases. Delay in surgery resulted in
      cerebral abscess in 1 patient. Surgery was performed in all the patients: wound
      debrident, duroplasty, and reduction of fracture in 3 patients and craniotomy
      with excision of abscess in 1 patient. Two of the patients did well after
      surgery. The patients with abscess died 9 days after surgery. Another patient
      developed CSF fistula after surgery, and died of aspiration while waiting for the
      closure of the fistula. CONCLUSION: Elevated skull fractures in our series were
      all compound fractures. Both long, sharp objects as well as blunt objects can
      cause this injury. Delay in surgery could result in intracranial sepsis. We
      suggest that this fracture should be included in the classification of skull
      fractures.

PMID- 16630919
TI  - Intracranial dural arteriovenous fistula associated with progressive cervical
      myelopathy and normal venous drainage of the thoracolumbar cord: case report and
      review of the literature.
AB  - BACKGROUND: Intracranial dural arteriovenous malformations draining into the
      perimedullary venous system are rare lesions. In these cases, the selective
      spinal catheterization of all vessels with potential of causing that malformation
      was negative, and additional cerebral angiography usually reveals the fistula.
      Because of venous congestion of the cord caused by the DAVF, a delayed drainage
      or stagnation of contrast material in the artery of Adamkiewicz was considered as
      a compelling angiographic disorder so far. CASE DESCRIPTION: We report about a 58
      year-old patient with a DAVF of the right posterior fossa draining into the
      cervical and upper thoracic plexus of medullary veins, followed by progressive
      cervical myelopathy and a normal venous drainage of the artery of Adamkiewicz.
      Because of the failing endovascular treatment option, the neurosurgical
      intervention was performed. The fistula was explored and clipped without any
      complications. Immediately after operation, the patient reported an improvement
      of his neurological deficits. CONCLUSION: About 38 cases of intracranial DAVFs
      draining into the perimedullary venous system are reported, but to our knowledge,
      this is the second one with a normal drainage of the artery of Adamkiewicz. The
      pathophysiological mechanisms, diagnostic procedures, and treatment modalities
      are discussed.

PMID- 16630920
TI  - Tentorial dural arteriovenous fistula presenting symptoms due to mass effect on
      the dilated draining vein: case report.
AB  - BACKGROUND: Tentorial dural arteriovenous fistula (AVF) presented symptoms due to
      mass effect on the dilated draining vein. We report a patient presenting left
      hemisensory disturbance because of compression of the midbrain by a dilated
      draining vein of the AVF. The AVF has disappeared completely by drainer clipping
      after feeder embolization. CASE DESCRIPTION: A 66-year-old woman presented with
      left hemisensory disturbance due to compression of the midbrain by a dilated
      draining vein with tentorial dural AVF. On admission, she complained of left
      hemisensory disturbance. Enhanced computed tomography (CT), magnetic resonance
      imaging, and magnetic resonance angiogram revealed the midbrain compressed by a
      mass lesion, which was a draining vein with AVF fed by numerous feeding arteries
      neighboring the right tentorial edge. The single-photon emission CT (SPECT) did
      not depict any laterality. CONCLUSION: This is a rare case of a tentorial dural
      AVF which caused left hemisensory disturbance not by venous congestion, but by a
      compression of the midbrain by the dilated draining vein, because SPECT showed no
      laterality. In this case, magnetic resonance angiogram, 3-dimensional CT
      angiography, and SPECT were useful in the diagnosis and planning the strategy for
      treatment.

PMID- 16630921
TI  - Cavernous sinus dural arteriovenous fistula complicated by pontine venous
      congestion. A case report.
AB  - BACKGROUND: Brainstem venous congestion is a rare but serious complication of the
      CS-dAVF (cavernous sinus dural arteriovenous fistual). CASE DESCRIPTION: A 71
      year-old woman presented with right abducens nerve palsy. Brain MRI showed a
      solitary lesion in the right upper pons. Cerebral angiogram revealed the right CS
      dAVF with retrograde venous drainage into the cerebellar cortical veins and the
      anterior pontomesencephalic vein. The patient was treated with stereotactic
      radiosurgery, resulting in complete resolution of the pontine lesion and the
      neurologic symptom. CONCLUSION: A solitary brainstem lesion can be caused by CS
      dAVF as a rare complication. Careful diagnosis and treatment are important to
      avoid permanent neurologic deficits.

PMID- 16630923
TI  - I told you it was going to happen... part II.

PMID- 16630924
TI  - Evaluation of motion produced in adjacent segments after use of an anterior
      cervical cage or artificial cervical disc: evaluation of a recently published
      study in the Journal of Neurosurgery Spine 2005.

PMID- 16630926
TI  - The Wiskott-Aldrich syndrome.
AB  - The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder with variable
      clinical phenotypes that correlate with the type of mutations in the WAS protein
      (WASP) gene. WASP, a key regulator of actin polymerization in hematopoietic
      cells, has 5 well-defined domains that are involved in signaling, cell
      locomotion, and immune synapse formation. WASP facilitates the nuclear
      translocation of nuclear factor kappaB and was shown to play an important role in
      lymphoid development and in the maturation and function of myeloid monocytic
      cells. Mutations of WASP are located throughout the gene and either inhibit or
      dysregulate normal WASP function. Analysis of a large patient population
      demonstrates a phenotype-genotype correlation: classic WAS occurs when WASP is
      absent, X-linked thrombocytopenia when mutated WASP is expressed, and X-linked
      neutropenia when missense mutations occur in the Cdc42-binding site. The progress
      made in dissecting the function of WASP has provided new diagnostic possibilities
      and has propelled our therapeutic strategies from conservative symptomatic
      treatment to curative hematopoietic stem cell transplantation and toward gene
      therapy.

PMID- 16630927
TI  - Molecular basis of common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is the most prevalent human primary
      immunodeficiency requiring medical attention. Until recently, the only known
      genetic defect specific to CVID was the inducible costimulatory receptor (ICOS)
      deficiency, which accounts for less than 1% of the patients. Recently, mutations
      in the TNF receptor family member transmembrane activator and calcium-modulator
      and cyclophilin ligand interactor (TACI), which mediates isotype switching in B
      cells, were found to be present in 10% to 20% of patients with CVID. Mutations in
      TACI were also found in relatives of patients with CVID who had IgA deficiency
      (IgAD), as well as in a patient with isolated IgAD. In the majority of patients
      described to date, only one TACI allele is mutated, showing an autosomal dominant
      transmission of the disease. B cells from individuals with TACI mutations did not
      produce IgG and IgA in response to the TACI ligand a proliferation-inducing
      ligand (APRIL), probably reflecting impaired isotype switching. These results
      suggest that TACI mutations can lead to CVID and IgAD.

PMID- 16630928
TI  - The last 80 years in primary immunodeficiency: how far have we come, how far need
      we go?

PMID- 16630930
TI  - Primary immunodeficiency or not? Making the correct diagnosis.
AB  - Making a correct diagnosis of a primary immunodeficiency disease is crucial for
      the selection of proper therapy. Although many cases go undiagnosed, there are
      also many instances of incorrect diagnosis that result in years of inappropriate
      treatment and failure to implement beneficial treatment. This article summarizes
      2 actual cases in which incorrect diagnoses led to recommendations of unwarranted
      high-risk or costly treatments. Had the physicians chosen tests of immune
      function rather than relying on immunoglobulin levels or cell counts, they would
      have arrived at the true diagnoses.

PMID- 16630931
TI  - Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the
      presence of anti-IgE (omalizumab).
AB  - BACKGROUND: Although serological IgE measurements can aid in efficacy assessment
      of patients with asthma on omalizumab (Xolair [Genentech, Inc., South San
      Francisco, Calif]; humanized IgG1 antihuman IgE Fc), its effect on clinically
      used IgE assay performance is unknown. OBJECTIVE: This study investigated the
      hypothesis that IgE:IgG-anti-IgE immune complex formation after omalizumab
      administration diminishes accuracy and increases variability of IgE assays
      performed in diagnostic immunology laboratories. METHODS: Plasma from 4 atopic
      adults was incubated with omalizumab (50 or 200 molar excess to IgE) or buffer.
      Paired specimens were sent masked to 159 clinical laboratories in the College of
      American Pathologists Diagnostic Allergy Proficiency Survey (cycles SE-C-2003, SE
      A-2005). Inhibitory effects produced by omalizumab on accuracy and
      reproducibility of US Food and Drug Administration (FDA)-cleared total and
      allergen-specific IgE assays were computed by using national proficiency survey
      data. RESULTS: Total serum IgE levels measured in the 2 ImmunoCAP assays were
      minimally reduced (2.4-9.0%) by the presence of omalizumab, whereas 5 other
      assays showed marked reductions from 12.5% to 67.2% (P < .001) that increased in
      proportion to total serum IgE levels. The degree of interference was not large
      enough to produce detectable misclassification of IgE antibody results (positive
      to negative) in 4 multiallergen screening assays. Of 11 FDA-cleared IgE antibody
      assays, only 3 (ImmunoCAP, UniCAP, Immulite-2000) generated quantitative IU/mL
      results that could be assessed for interference. Omalizumab produced 0.8% to
      27.8% reduction in allergen-specific IgE levels across 8 allergen specificities.
      CONCLUSION: Although as much as 62% loss in accuracy was observed in FDA-cleared
      human IgE assays, the ImmunoCAP system was sufficiently robust to provide
      accurate and reproducible total and allergen-specific IgE antibody results in a
      clinical setting where therapeutic levels of omalizumab are present in serum.
      CLINICAL IMPLICATIONS: Accurate monitoring of total and allergen-specific IgE,
      together with free IgE levels, in serum from patients on omalizumab may help
      optimize dosing and maximize the efficacy of Xolair therapy.

PMID- 16630932
TI  - Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004
      Summer Olympics.
AB  - BACKGROUND: The International Olympic Committee Medical Commission required a
      medical justification for athletes to inhale a beta2-agonist before an event at
      the Summer Games in Athens in 2004. OBJECTIVE: We sought to establish the
      percentage of athletes applying to use an inhaled beta2-agonist on the basis of
      the results of objective tests to establish a diagnosis of asthma or exercise
      induced bronchoconstriction. We also sought to compare this percentage with the
      percentage of athletes simply notifying the intention to use a beta2-agonist at
      the previous Summer Games in Sydney in 2000. METHODS: An analysis was made of
      tests that measured the change in FEV1 in response to a bronchodilator or in
      response to a provoking stimulus, such as exercise, eucapnic voluntary hyperpnea,
      hypertonic saline, or methacholine. RESULTS: Ten thousand six hundred fifty-three
      athletes competed in Athens; 4.2% were approved to use a beta2-agonist, and 0.4%
      were rejected. This approval rate was 26% less than the notifications in 2000 in
      Sydney (5.7%). Compared with Sydney 2000, there was a significant reduction of
      submissions and approvals for athletes from the United States, New Zealand,
      Australia, and Canada and in triathlon and swimming sports. CONCLUSION: The need
      to provide objective testing has resulted in a reduction in the number of
      athletes seeking approval to use an inhaled beta2-agonist. Objective evidence has
      provided information for the doctor that is likely to improve the health of the
      athlete because many athletes appeared to be undertreated at the time of testing.
      CLINICAL IMPLICATIONS: We show that documentation of airway narrowing in
      athletes, particularly in response to exercise or surrogate stimuli for exercise,
      aids in the diagnosis and management of asthma by providing evidence of bronchial
      hyperresponsiveness that will respond to treatment with inhaled corticosteroids
      and is usually associated with a reduction in respiratory symptoms on exercise.

PMID- 16630933
TI  - Association between genetic variations of vascular endothelial growth factor
      receptor 2 and atopy in the Korean population.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has been suggested to be a
      key mediator in the development of atopy and T(H)2 inflammation. OBJECTIVE: We
      sought to evaluate the effects of variations in the gene coding VEGF receptor
      (VEGFR) 2 on intermediate phenotypes of asthma in the Korean population. METHODS:
      A cohort of 2055 children and adolescents responded to a questionnaire concerning
      asthma symptoms and risk factors and underwent methacholine bronchial challenge
      and skin tests. The VEGFR2 gene, including the promoter area, was sequenced on 24
      healthy subjects to discover informative single nucleotide polymorphisms (SNPs;
      minor allele frequency >2%). After haplotype reconstruction, 4 tagging SNPs
      (IVS6+54A>G, +889G>A, +1416T>A, and IVS25-92G>A) were scored. These SNPs were
      also scored in 480 adult asthmatic patients to verify the above genetic
      association study. RESULTS: The prevalence of atopy was associated with a single
      SNP (+889G>A) of VEGFR2 with borderline significance (P = .048; relative risk,
      1.13; 95% CI, 1.00-1.28). However, haplotype analysis showed that the atopy
      prevalence was strongly associated with a haplotype (AGAG) of VEGFR2 (P = .002;
      relative risk, 1.25; 95% CI, 1.09-1.42). As for airway hyperresponsiveness,
      neither individual SNPs nor haplotypes were found to be associated.
      Interestingly, the significant association was also found between atopy and the
      AGAG haplotype among adult asthmatic patients (P = .008; odds ratio, 1.66; 95%
      CI, 1.14-2.44). CONCLUSIONS: The present study demonstrated that genetic
      variations of VEGFR2 are significantly associated with atopy in the Korean
      population.

PMID- 16630934
TI  - Reduced airway hyperresponsiveness and tracheal responses during allergic asthma
      in mice lacking tyrosine kinase inducible T-cell kinase.
AB  - BACKGROUND: Patients with allergic asthma have symptoms of a predominant T(H)2
      response, including airway eosinophilic inflammation and increased mucous
      production in the lungs. This accompanies increased airways responsiveness, which
      can be life threatening. Because T(H)2 cells and cytokines have been implicated
      in contributing to these symptoms, pathways that control the development of these
      cells or that regulate their cytokine production represent good targets for
      controlling this disease. OBJECTIVE: We have previously shown that mice lacking
      the tyrosine kinase inducible T-cell kinase (ITK) have drastically reduced airway
      inflammation in a model of allergic asthma. However, it was not clear whether
      this translated into reduced airways hyperresponsiveness. We have analyzed
      tracheal responsiveness and airways hyperresponsiveness of wild-type (WT) and ITK
      null mice during induction of experimental allergic asthma. METHODS: Experimental
      allergic asthma was induced in WT and ITK knockout mice. Tracheal responses to
      carbachol, acetylcholine, and potassium chloride were analyzed. Airways
      hyperresponsiveness to methacholine challenge was also analyzed in allergen
      challenged mice, along with lung and bronchoalveolar lavage fluid T(H)2 cytokine
      message and protein. RESULTS: ITK null mice have reduced tracheal responses to
      cholinergic challenge in vitro before as well as after allergen challenge. These
      mice also have reduced airways hyperresponsiveness in response to allergen
      challenge, which could be rescued by transferring WT splenocytes or purified WT
      CD4+ T cells. This reduced airways response was preferentially accompanied by
      reduced expression of T(H)2 cytokines in the lungs. CONCLUSION: Our results
      indicate that the tyrosine kinase ITK and its function in T cells represent an
      attractive target for antiasthmatic drugs. CLINICAL IMPLICATIONS: Modulating the
      expression or activity of ITK may be a novel strategy to block allergic airway
      inflammation.

PMID- 16630935
TI  - Airway epithelial cells produce neurotrophins and promote the survival of
      eosinophils during allergic airway inflammation.
AB  - BACKGROUND: Eosinophil-epithelial cell interactions make a major contribution to
      asthmatic airway inflammation. Nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), and other members of the neurotrophin family,
      originally defined as a class of neuronal growth factors, are now recognized to
      support the survival and activation of immune cells. Neurotrophin levels are
      increased in bronchoalveolar lavage fluid during allergic asthma. OBJECTIVE: We
      sought to investigate the role of neurotrophins as inflammatory mediators in
      eosinophil-epithelial cell interactions during the allergic immune response.
      METHODS: Neurotrophin expression in the lung was investigated by means of
      immunohistochemistry and ELISA in a mouse model of chronic experimental asthma.
      Coculture experiments were performed with airway epithelial cells and
      bronchoalveolar lavage fluid eosinophils. RESULTS: Neurotrophin levels increased
      continuously during chronic allergic airway inflammation, and airway epithelial
      cells were the major source of NGF and BDNF within the inflamed lung. Epithelial
      neurotrophin production was upregulated by IL-1beta, TNF-alpha, and T(H)2
      cytokines. Lung eosinophils expressed the BDNF and NGF receptors tropomyosin
      related kinase (Trk) A and TrkB, and coculture with airway epithelial cells
      resulted in enhanced epithelial neurotrophin production, as well as in prolonged
      survival of eosinophils. Eosinophil survival was completely abolished in the
      presence of the neurotrophin receptor Trk antagonist K252a. CONCLUSION: During
      allergic inflammation, airway epithelial cells express increased amounts of NGF
      and BDNF that promote the survival of tissue eosinophils. Controlling epithelial
      neurotrophin production might be an important therapeutic target to prevent
      allergic airway eosinophilia. CLINICAL IMPLICATIONS: Attenuating the release of
      inflammatory mediators from the activated airway epithelium will become an
      important strategy to disrupt the pathogenesis of chronic allergic asthma.

PMID- 16630936
TI  - IL-17F sequence variant (His161Arg) is associated with protection against asthma
      and antagonizes wild-type IL-17F activity.
AB  - BACKGROUND: IL-17F is a recently discovered cytokine that plays a role in tissue
      inflammation by inducing release of proinflammatory and neutrophil-mobilizing
      cytokines. Upregulated IL17F gene expression has been observed at sites of
      allergen challenge in the airways of patients with asthma, suggesting that IL-17F
      is involved in the pathophysiology of asthma. OBJECTIVE: To investigate the role
      of IL-17F in asthma pathogenesis, we conducted genetic analyses of association of
      asthma with the common variants of IL17F, using 867 unrelated Japanese subjects.
      METHODS: Five polymorphisms were studied, including the coding-region sequence
      variant single nucleotide polymorphism rs763780 (7488T/C), which causes a His-to
      Arg substitution at amino acid 161 (H161R). Functional consequences of the H161R
      substitution were examined by using recombinant wild-type and mutant IL-17F
      proteins. RESULTS: Homozygosity of the H161R variant was inversely associated
      with asthma; the odds ratio (95% CI) for asthma was 0.06 (0.01-0.43) for the
      H161R homozygote compared with the wild-type homozygote (P = .0039). This result
      remains significant (P = .0079) after adjustment for the presence of atopy using
      the Mantel-Haenszel chi2 test. In addition, in vitro functional experiments
      demonstrated that the H161R variant of IL-17F lacks the ability to activate the
      mitogen-activated protein kinase pathway, cytokine production, and chemokine
      production in bronchial epithelial cells, unlike wild-type IL-17F. Furthermore,
      the H161R variant blocked induction of IL-8 expression by wild-type IL-17F.
      CONCLUSION: The current findings indicate that the IL-17F H161R variant
      influences the risk of asthma and is a natural IL-17F antagonist, suggesting a
      potential role for IL-17F in the etiology of asthma.

PMID- 16630937
TI  - Sublingual immunotherapy with once-daily grass allergen tablets: a randomized
      controlled trial in seasonal allergic rhinoconjunctivitis.
AB  - BACKGROUND: Specific immunotherapy is the only treatment modality that has the
      potential to alter the natural course of allergic diseases. Sublingual
      immunotherapy has been developed to facilitate access to this form of treatment
      and to minimize serious adverse events. OBJECTIVE: To investigate the efficacy
      and safety of sublingual grass allergen tablets in seasonal allergic
      rhinoconjunctivitis. METHODS: A multinational, multicenter, randomized, placebo
      controlled trial conducted during 2002 and 2003. Fifty-five centers in 8
      countries included 855 participants age 18 to 65 years who gave a history of
      grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick
      test and elevated serum allergen-specific IgE to Phleum pratense. Participants
      were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX;
      ALK-Abello, Horsholm, Denmark) or placebo for sublingual administration once
      daily. Mean duration of treatment was 18 weeks. RESULTS: Average
      rhinoconjunctivitis scores during the season showed moderate reductions of
      symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T
      (P = .0710; P = .0470) compared with placebo. Significantly better
      rhinoconjunctivitis quality of life scores (P = .006) and an increased number of
      well days (P = .041) were also observed. Efficacy was increased in the subgroup
      of patients who completed the recommended preseasonal treatment of at least 8
      weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication
      use, 29%, P = .0120). No safety concerns were observed. CONCLUSION: This study
      confirms dose-dependent efficacy of the grass allergen tablet. Although further
      studies are required, the greater tolerability of the tablet may permit
      immunotherapy to be available to a much broader group of patients with impaired
      quality of life caused by grass pollen allergy. CLINICAL IMPLICATIONS: For
      patients with grass pollen allergy, sublingual immunotherapy is well tolerated
      and can reduce symptoms and improve quality of life.

PMID- 16630938
TI  - Double-blind, placebo-controlled study with a modified therapeutic vaccine of
      Salsola kali (Russian thistle) administered through use of a cluster schedule.
AB  - BACKGROUND: The inhalation of Salsola kali pollen is a common cause of
      respiratory diseases in Europe and North America. OBJECTIVE: To evaluate the
      efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic
      vaccine of S kali. METHODS: The trial was randomized, double-blind, and placebo
      controlled using a rush protocol in the build-up phase. Sixty patients with
      rhinoconjunctivitis (19 also had mild asthma) were randomly allocated to receive
      either active treatment (polymerized extract) or placebo. The final distribution
      was 41 patients in the active and 19 in the placebo group. Side effects were
      registered. Symptom and medication scores and the number of days free of symptoms
      during the pollen season were assessed to evaluate the clinical efficacy. A
      Rhinoconjunctivitis Quality of Life Questionnaire was completed in the previous
      pollen season (before treatment) and during the pollen season 1 year later (in
      the trial). Dose-response skin tests were performed at baseline and at the end of
      the trial. RESULTS: There was a significant difference (P < .05) in symptom and
      medication scores between both groups during the pollen season, with the active
      group the one that had fewer symptoms and lower intake of medication. The number
      of days without symptoms was higher in the active group (P < .05). This group
      also had a significant improvement in the Rhinoconjunctivitis Quality of Life
      Questionnaire and a reduction in skin sensitivity. No moderate or severe systemic
      reactions were registered. CONCLUSION: Immunotherapy with this modified vaccine
      of S kali pollen is safe and efficacious to treat patients clinically sensitive
      to this pollen. CLINICAL IMPLICATIONS: Patients allergic to S kali (Russian
      thistle) can be successfully treated with immunotherapy to improve symptoms of
      allergic rhinitis and asthma, reduce medication use, and improve quality of life
      parameters.

PMID- 16630939
TI  - Prenatal farm exposure is related to the expression of receptors of the innate
      immunity and to atopic sensitization in school-age children.
AB  - BACKGROUND: There is increasing evidence that environmental exposures determining
      childhood illnesses operate early in life. Prenatal exposure to a farming
      environment through the mother might also play an important role. OBJECTIVE: We
      sought to investigate the role of maternal exposures to environments rich in
      microbial compounds for the development of atopic sensitization, asthma, and
      corresponding alterations in the innate immune system in offspring. METHODS: In
      the children of the cross-sectional Prevention of Allergy Risk Factors for
      Sensitization in Children Related to Farming and Anthroposophic Life Style study,
      asthma and atopy were assessed by means of standardized questionnaires (n = 8263)
      and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression
      of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures
      were defined through questionnaire information. RESULTS: Both atopic
      sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene
      expression of receptors of innate immunity were strongly determined by maternal
      exposure to stables during pregnancy, whereas current exposures had much weaker
      or no effects. A dose-response relation was found between the extent of
      upregulation of these genes and the number of different farm animal species the
      mother had encountered in her pregnancy. Each additional farm animal species
      increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI,
      1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively.
      CONCLUSION: Maternal exposure to an environment rich in microbial compounds might
      protect against the development of atopic sensitization and lead to upregulation
      of receptors of the innate immune system. The underlying mechanisms potentially
      operating through the intrauterine milieu or epigenetic inheritance await further
      elucidation. CLINICAL IMPLICATIONS: When assessing risk factors of allergies in
      an infant's medical history, attention must also be paid to environmental
      exposures affecting the mother.

PMID- 16630940
TI  - Effects of ultrafine carbon particle inhalation on allergic inflammation of the
      lung.
AB  - BACKGROUND: Epidemiologic studies show that exposure to particulate air pollution
      is associated with asthma exacerbation. Ultrafine particles (diameter <100 nm)
      may contribute to these adverse effects. OBJECTIVE: To investigate potential
      adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on
      allergic airway inflammation. METHODS: The effects of ultrafine particle
      inhalation on allergic airway inflammation was analyzed in ovalbumin-sensitized
      mice and nonsensitized controls. Particle exposure (526 microg/m3, 24 hours) was
      performed 24, 96, or 168 hours before or 24 or 72 hours after ovalbumin aerosol
      challenge. Allergic inflammation was analyzed at different time points after
      allergen challenge by means of bronchoalveolar lavage cell count and
      cytokine/total protein assays, lung histology, and airway hyperresponsiveness.
      RESULTS: In sensitized mice, inhalation of ultrafine particles 24 hours before
      allergen challenge caused a significant increase of bronchoalveolar lavage
      inflammatory cell infiltrate, protein, IL-4, IL-5, and IL-13 compared with
      relevant controls. These adjuvant effects were dose- and time-dependent and were
      still present when particle exposure was performed 4 days before allergen
      challenge. The adjuvant effect of ultrafine particles was also documented by
      increased mucus production, peribronchiolar and perivascular inflammation, and
      enhanced airway hyperresponsiveness. In contrast, particle exposure in sensitized
      mice after allergen challenge caused only moderate effects, such as a delay of
      inflammatory infiltrate and a reduction of cytokines in bronchoalveolar lavage
      fluid. CONCLUSION: Exposure to ultrafine carbon particles before allergen
      challenge exerts strong adjuvant effects on the manifestation of allergic airway
      inflammation. Allergen-sensitized individuals may therefore be more susceptible
      to detrimental health effects of ultrafine particles.

PMID- 16630941
TI  - Effect of codeine on objective measurement of cough in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Codeine is the standard antitussive treatment to which novel agents
      are compared. Little is known about the objective effect of any treatments on
      cough in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To quantify the
      effect of codeine on objective cough frequency (quantified as time spent
      coughing: cough seconds, cs/h), citric acid cough threshold, and subjective
      measures in a double-blind, placebo-controlled crossover study in COPD. METHODS:
      We studied 21 patients with physician-diagnosed, stable disease who complained of
      cough (76.9% male; mean age, 67.7 years; mean predicted FEV(1), 53.4%; median
      smoking history, 43.5 pack-years). Each subject performed a cough challenge
      (single breath, citric acid), 10-hour daytime ambulatory and overnight cough
      recordings, subjective cough scores, and visual analog scales at baseline and on
      2 study days, 1 week apart. Codeine phosphate 60 mg or matched placebo were
      given, in random order, at the start of each cough recording (0 and 12 hours).
      RESULTS: Median time spent coughing at baseline was 8.27 cs/h (interquartile
      range [IQR], 5.94-11.67); after placebo treatment, 7.22 cs/h (IQR 4.42-10.40);
      and after codeine treatment, 6.41 cs/h (IQR 3.86-9.10). Codeine treatment had a
      significant effect on time spent coughing compared with baseline (P = .02) but
      not compared with placebo (P = .52). There were no significant differences in
      cough challenge thresholds (log concentration of tussive agent causing 2 coughs
      or log concentration of tussive agent causing 5 coughs) or subjective cough
      measures for codeine compared with placebo. CONCLUSION: In this study, codeine
      was no more effective than placebo in patients with COPD complaining of cough.
      CLINICAL IMPLICATIONS: Codeine is the antitussive agent to which we compare new
      treatments; however, in a group of stable patients with COPD, it had no effect on
      cough frequency over placebo.

PMID- 16630942
TI  - Cathelicidin deficiency predisposes to eczema herpeticum.
AB  - BACKGROUND: The cathelicidin family of antimicrobial peptides is an integral
      component of the innate immune response that exhibits activity against bacterial,
      fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of
      patients with atopic dermatitis (AD) because of disseminated infection with
      herpes simplex virus (HSV). OBJECTIVE: This study investigated the potential role
      of cathelicidins in host susceptibility to HSV infection. METHODS: Glycoprotein D
      was measured by means of real-time RT-PCR as a marker of HSV replication in skin
      biopsy specimens and human keratinocyte cultures. Cathelicidin expression was
      evaluated in skin biopsy specimens from patients with AD (n = 10) without a
      history of HSV skin infection and from patients with ADEH (n = 10). RESULTS: The
      cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in
      an antiviral assay, with significant killing (P < .001) within the physiologic
      range. The importance of cathelicidins in antiviral skin host defense was
      confirmed by the observation of higher levels of HSV-2 replication in
      cathelicidin-deficient (Cnlp-/-) mouse skin (2.6 +/- 0.5 pg HSV/pg GAPDH, P <
      .05) compared with that seen in skin from their wild-type counterparts (0.9 +/-
      0.3). Skin from patients with ADEH exhibited significantly (P < .05) lower levels
      of cathelicidin protein expression than skin from patients with AD. We also found
      a significant inverse correlation between cathelicidin expression and serum IgE
      levels (r2 = 0.46, P < .05) in patients with AD and patients with ADEH.
      CONCLUSION: This study demonstrates that the cathelicidin peptide LL-37 possesses
      antiviral activity against HSV and demonstrates the importance of variable skin
      expression of cathelicidins in controlling susceptibility to ADEH. Additionally,
      serum IgE levels might be a surrogate marker for innate immune function and serve
      as a biomarker for which patients with AD are susceptible to ADEH. CLINICAL
      IMPLICATIONS: A deficiency of LL-37 might render patients with AD susceptible to
      ADEH. Therefore increasing production of skin LL-37 might prevent herpes
      infection in patients with AD.

PMID- 16630943
TI  - Skin prick test to egg white provides additional diagnostic utility to serum egg
      white-specific IgE antibody concentration in children.
AB  - BACKGROUND: Levels of IgE antibody to egg white of greater than 7 kIU/L are
      highly predictive of clinical reactivity to egg, and lower levels often require
      evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs
      have inherent risks, and diagnostic criteria indicating high likelihood of
      passing would be clinically useful. OBJECTIVE: We sought to determine whether the
      size of the skin prick test (SPT) to egg white adds diagnostic utility for
      children with low egg white-specific IgE antibody levels. METHODS: A
      retrospective analysis of clinical history, egg white-specific IgE antibody
      levels, SPT responses, and egg OFC outcomes was performed. RESULTS: Children who
      passed (n = 29) egg OFCs and those who failed (n = 45) did not differ
      significantly in age, clinical characteristics, or egg white-specific IgE levels.
      There were, however, significant differences between both egg white SPT wheal
      response size and egg/histamine SPT wheal index. Children who failed egg OFCs had
      a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P =
      .003). Children who failed egg OFCs had a median egg/histamine index of 1.00;
      those who passed had a median index of 0.71 (P = .001). For egg white-specific
      IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index
      of 0.65 was associated with a 50% chance of passing. CONCLUSION: In children with
      low egg white-specific IgE levels, those with smaller SPT wheal responses to egg
      were more likely to pass an egg OFC than those with larger wheal responses. The
      size of the egg white SPT response might provide additional information to
      determine the timing of egg OFC. CLINICAL IMPLICATIONS: The size of the egg white
      SPT wheal response might provide the clinician with additional information to
      determine the timing of egg OFC in children with low egg white-specific IgE
      antibody levels.

PMID- 16630944
TI  - Molecular cloning and expression in insect cells of honeybee venom allergen acid
      phosphatase (Api m 3).
AB  - BACKGROUND: Acid phosphatase (Api m 3) is a major allergen in honeybee (Apis
      mellifera) venom, and its availability as a recombinant protein may facilitate
      the development of improved diagnostic tests and immunotherapies. OBJECTIVE: One
      objective is the determination of the complete primary structure of Api m 3 and
      to obtain recombinant Api m 3 on the basis of expression in insect cells. Another
      objective is the quantitative analysis of patient serum IgE antibody reactive to
      recombinant Api m 3. METHODS: The cloning of Api m 3 from venom gland cDNA and
      its expression as a full-length protein in eukaryotic insect cells is described.
      The immunoreactivity of serum IgE antibodies of honeybee venom-sensitized
      patients to recombinant Api m 3 was determined in an enzyme immunoassay. RESULTS:
      PCR amplification generated a 1122-bp DNA fragment whose identity as the coding
      sequence of Api m 3 was verified by several means. Recombinant Api m 3, expressed
      in Trichoplusia ni cells, showed an expected molecular weight and enzymatic
      activity at pH 4.5. Analysis of tryptic fragments of purified recombinant Api m 3
      by mass spectrometry confirmed its identity. In immunoassays, recombinant Api m 3
      is specifically recognized by IgE antibodies of pooled serum in Western blots and
      by 37% of the individual sera of honeybee venom-sensitized patients in ELISA
      analysis. CONCLUSION: The availability of recombinant Api m 3 provides a tool for
      both the development of improved diagnostic tests and the design of safer and
      more effective immunotherapeutic approaches for honeybee venom allergy. CLINICAL
      IMPLICATIONS: The recombinant venom allergen Api m 3 is a key element in the
      search for an optimized component-resolved approach to honeybee venom allergy
      with regard to both the development of superior diagnostic tests and the
      improvement of allergen immunotherapy.

PMID- 16630945
TI  - Defects of class-switch recombination.
AB  - Shaping of the secondary antibody repertoire is generated by means of class
      switch recombination (CSR), which replaces IgM with other isotypes, and somatic
      hypermutation (SHM), which allows production of high-affinity antibodies.
      However, the molecular mechanisms underlying these important processes have long
      remained obscure. Immunodeficiency with hyper-IgM comprises a group of
      genetically heterogeneous defects of CSR variably associated with defects of SHM.
      The study of these patients has allowed us to recognize that both T-cell-B-cell
      interaction (resulting in CD40-mediated signaling) and intrinsic B-cell
      mechanisms are involved in CSR and SHM. Elucidation of the molecular defects
      underlying these disorders has been essential to better understand the molecular
      basis of Ig diversification and has offered the opportunity to define the
      clinical spectrum of these diseases and to prompt more accurate diagnostic and
      therapeutic approaches.

PMID- 16630946
TI  - Gene therapy for immune disorders: good news tempered by bad news.
AB  - After a dozen years of human gene therapy trials characterized by minimal gene
      correction and disappointing clinical impact, the field of gene therapy received
      some good news in 2000. Infants with X-linked severe combined immunodeficiency
      who received retroviral gene addition to cells from their bone marrow developed
      impressive immune reconstitution. During the following 2 years, additional
      patients were treated and the news was even better-babies receiving gene therapy
      had sustained T-cell production and in several cases developed better cell
      function than most patients treated with standard bone marrow transplants.
      Unfortunately, bad news followed. Three of the patients experienced leukemic T
      cell expansions, found to be associated with retroviral insertions into genomic
      DNA. Where does the field stand today?

PMID- 16630947
TI  - TACI mutation with invasive polyclonal CD8+ T-cell lymphoproliferation in a
      patient with common variable immunodeficiency.
AB  - Mutations of the gene encoding the TNF receptor family member transmembrane
      activator and calcium-modulator and cyclophilin ligand interactor (TACI),
      TNFSRF13B, have recently been described in patients with common variable
      immunodeficiency (CVID). We report the case of a man with CVID in association
      with a heterozygous TACI gene mutation (C104R) who had a highly unusual,
      invasive, polyclonal CD8+ T-cell lymphoproliferation resulting in massive
      hepatosplenomegaly and causing renal impairment because of infiltration. Although
      lymphoproliferation is well described in CVID, the key features in this patient
      included the T-cell origin of the lymphoproliferation, its polyclonal nature, its
      infiltration into multiple organs, and the presence of the TACI gene mutation.

PMID- 16630948
TI  - Etanercept treatment of cutaneous granulomas in common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency
      characterized by hypogammaglobulinemia, poor antibody responses, and recurrent
      bacterial infections, usually of the sinorespiratory tract. A not uncommon
      complication is granuloma of the lungs, spleen, liver, and/or skin. We report the
      case of an 18-year-old boy with CVID and chronic granulomas of the left arm
      (since 13 years of age) refractory to treatment with antibiotics, intravenous
      immunoglobulin, antifungal agents, systemic and intralesional steroids, IFN
      gamma, cyclosporine, methotrexate, hydroxychloroquine, localized radiation
      therapy, and surgical excision. The lesions improved after treatment with the
      systemic administration of the TNF-alpha inhibitor etanercept for 1 year.
      Etanercept prevents soluble TNF from binding to its cell membrane receptor,
      leading to inhibition of its inflammatory cascade. We recommend further trials of
      etanercept in patients with CVID with noninfectious recalcitrant granulomas.

PMID- 16630949
TI  - Mutations in the RNA component of RNase mitochondrial RNA processing might cause
      Omenn syndrome.
AB  - BACKGROUND: Omenn syndrome is a variant of severe combined immunodeficiency
      disease, which most prominently presents with erythroderma, eosinophilia, and
      susceptibility to various pathogens. Mutations in the nucleases of recombination
      activating genes 1 and 2 (RAG1/RAG2) or Artemis were found in some, but not all,
      patients with Omenn syndrome. We identified 2 patients who presented with
      clinical features consistent with Omenn syndrome but had no mutations in RAG or
      Artemis. Both patients also had cartilage-hair hypoplasia (CHH). OBJECTIVES: We
      sought to define the molecular basis and characterize the features of severe
      combined immunodeficiency and Omenn syndrome in these patients. METHODS: We have
      studied humoral and cellular immunity using standard assays. T-cell repertoire
      was investigated by quantitating Vbeta families. The RNase mitochondrial RNA
      processing (RMRP) RNA gene was sequenced by using standard techniques. RESULTS:
      Sequence analysis of the RMRP RNA gene showed that each patient had an insertion
      duplication on one allele and a point mutation on the other allele. These point
      mutations were novel, and they might be related to the unusual presentation of
      Omenn syndrome in addition to CHH in these patients. Indeed, analysis of the
      thymus showed residual mature T lymphocytes. This leaky thymus might be
      responsible for the skewed release of some T-cell clones into the circulation,
      which might trigger the phenotype of Omenn syndrome. CONCLUSION: We have
      demonstrated that mutations in the RMRP RNA gene might be associated with Omenn
      syndrome. CLINICAL IMPLICATIONS: This discovery will aid clinicians in the early
      recognition and treatment of CHH-associated Omenn syndrome.

PMID- 16630950
TI  - Self-administration of C1-inhibitor concentrate in patients with hereditary or
      acquired angioedema caused by C1-inhibitor deficiency.
AB  - BACKGROUND: Administration of C1-inhibitor concentrate is effective for
      prophylaxis and treatment of severe angioedema attacks caused by C1-inhibitor
      deficiency. The concentrate should be administered intravenously and hence needs
      to be administered by health care professionals, which might cause considerable
      delay in treatment and inconvenience for patients. OBJECTIVE: The aim of this
      study was to investigate the feasibility, efficacy, and safety of on-demand and
      prophylactic self-administration of C1-inhibitor concentrate in patients with
      frequent attacks of angioedema. METHODS: Patients with hereditary or acquired C1
      inhibitor deficiency who had very frequent angioedema attacks were trained to
      self-administer C1-inhibitor concentrate. The study consisted of 31 patients
      using on-demand treatment and 12 patients using prophylaxis with C1-inhibitor
      concentrate. Mean follow-up was 3.5 years. RESULTS: All patients were capable of
      self-administering the concentrate, with technical failure rates of self
      injection being less than 2%. Times between the onset of the attack and the
      initiation of relief or complete resolution of symptoms in the on-demand group
      were significantly shortened (2.2 hours and 7.9 hours, respectively) compared
      with the situation before the start of self-administration. In the prophylaxis
      group self-administration of C1-inhibitor concentrate decreased the angioedema
      attack rate from 4.0 to 0.3 attacks per month. CONCLUSION: Intravenous self
      administration of C1-inhibitor concentrate is a feasible and safe option and
      results in more rapid and more effective treatment or prevention of severe
      angioedema attacks in patients with C1-inhibitor deficiency. CLINICAL
      IMPLICATIONS: Self-administration of C1-inhibitor concentrate could be a valuable
      and convenient treatment modality to prevent or treat angioedema attacks in
      patients with C1-inhibitor deficiency.

PMID- 16630952
TI  - Decreased CD4+ lymphocytes and innate immune responses in adults with previous
      extrapulmonary tuberculosis.
AB  - BACKGROUND: CD4+ lymphocytes control Mycobacterium tuberculosis infection through
      cytokine-mediated macrophage activation. Extrapulmonary tuberculosis is
      presumably a marker of immunodeficiency, but cytokine responses have not been
      well studied in such patients. OBJECTIVE: Assess immune defects in persons with
      previous extrapulmonary tuberculosis. METHODS: In vitro cytokine responses of
      PBMCs from HIV-seronegative adults with previous extrapulmonary tuberculosis (n =
      10) were compared with responses from persons with previous pulmonary
      tuberculosis (n = 24) and latent M tuberculosis infection (n = 30) in a case
      control study. RESULTS: Patients and controls did not differ according to age,
      sex, race, or monocytes. The median time between tuberculosis diagnosis and study
      entry was 72 and 122 weeks in extrapulmonary and pulmonary patients, respectively
      (P = .2). Median CD4+ counts were 660, 814, and 974 lymphocytes/mm3 in
      extrapulmonary, pulmonary, and latently infected patients, respectively (P =
      .03). At 48 hours, median unstimulated cytokine levels were uniformly lower in
      extrapulmonary patients than both sets of controls. These differences persisted
      after controlling for CD4+ count by linear regression analysis. Despite lower
      unstimulated levels, median TNF-alpha response was higher in patients with
      extrapulmonary and pulmonary tuberculosis than latently infected persons after
      stimulation with PHA 1% (P = .006) and PHA+IL-12 (1 ng/mL; P = .02); IL-10
      remained low in patients with extrapulmonary tuberculosis after the same stimuli
      (P = .04 and .06, respectively). There was no primary immunodeficiency in the IL
      12/23-IFN-gamma axis. CONCLUSION: HIV-seronegative adults with previous
      extrapulmonary tuberculosis had lower CD4+ lymphocytes and unstimulated cytokine
      production. This suggests a subtle abnormality in innate immune function.
      CLINICAL IMPLICATIONS: These characteristics could identify persons at risk for
      severe tuberculosis manifestations.

PMID- 16630951
TI  - Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected
      children during successful highly active antiretroviral therapy.
AB  - BACKGROUND: In a cohort of children receiving highly active antiretroviral
      therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who
      reached undetectable RNA after week 8 (slow responders, median: week 20) had
      higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte
      counts compared with children who reached undetectable plasma HIV-1 RNA by week 8
      (rapid responders) throughout HAART. OBJECTIVE: To determine whether levels of T
      cell receptor excision circles (TRECs) could explain the apparent inconsistency
      between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected
      children receiving HAART with sustained virologic suppression. METHODS: T-cell
      receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified
      longitudinally by PCR in 31 children (median age, 5.6 years) with sustained
      undetectable plasma HIV-1 RNA for >104 weeks of HAART. RESULTS: There was a
      positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48
      and 80 (P < .004). During the early stage of HAART, TREC levels positively
      correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T
      lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were
      consistently equal or higher in slow responders compared with rapid responders (P
      < .001) despite slow responders having consistently greater quantities of HIV-1
      DNA. CONCLUSION: To maintain adequate levels of CD4+ T-lymphocytes, children with
      high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic
      control mechanism is required to maintain new CD4+ T lymphocytes in the presence
      of persistent virus. CLINICAL IMPLICATIONS: The TREC level is a useful marker of
      thymic function in HIV-infected children.

PMID- 16630953
TI  - Leukotriene D4 enhances immunoglobulin production in CD40-activated human B
      lymphocytes.
AB  - BACKGROUND: Cysteinyl-leukotrienes (cysLTs) are lipid mediators recognized for
      their role in asthma and allergic inflammation. CysLT1, one of the receptors for
      cysLTs, is expressed, among others, in bronchial smooth muscle cells, phagocytes,
      and B lymphocytes. The potential role of CysLT1 in B lymphocytes remains
      unexplored. OBJECTIVE: We examined the modulation of expression and function of
      CysLT1 in human B lymphocytes. METHODS: Human B lymphocytes were purified from
      peripheral blood and analyzed by means of RT-PCR and flow cytometry, after
      culture with IL-4 and anti-CD40 antibody or CD154-transfected fibroblasts.
      Functional responses to leukotriene (LT) D4 in terms of cytosolic calcium flux,
      proliferation, and immunoglobulin production were also examined. RESULTS: B
      lymphocytes expressed CysLT1 at both the mRNA and protein levels. Two-fold to 3
      fold enhancement of CysLT1 expression was observed after B-cell exposure to a
      combination of activating anti-CD40 antibody and IL-4. The expression of CysLT1
      was also enhanced when B lymphocytes were cocultured with CD154-transfected
      fibroblasts in the presence of IL-4. Moreover, IL-4 and CD40-activated B
      lymphocytes showed an increased responsiveness to LTD4 in terms of cytosolic
      calcium flux, which was totally prevented by the selective CysLT1 antagonist
      montelukast. Stimulation of IL-4 and CD40-activated B lymphocytes with picomolar
      concentrations of LTD4 induced mature epsilon transcripts and upregulated IgE and
      IgG production 2-fold to 3-fold. CONCLUSION: We have demonstrated that expression
      of CysLT1 can be upregulated in B lymphocytes after stimulation with CD154, with
      consequent increased responsiveness of the cells to LTD4 in terms of
      immunoglobulin production. CLINICAL IMPLICATIONS: This study provides evidence
      that cysLTs generated during allergic reactions can affect B-cell function and
      enhance IgE and IgG production, which may further contribute to the allergic
      process.

PMID- 16630954
TI  - Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and
      IFN-gamma.
AB  - BACKGROUND: N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been
      hypothesized to have opposing influences on neonatal immune responses that might
      influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid
      (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development.
      OBJECTIVE: We evaluated whether cord blood fatty acid levels were related to
      neonatal immune responses and whether n-3 and n-6 PUFA responses differed.
      METHODS: We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n =
      192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n =
      191) and cytokine (IL-13 and IFN-gamma; n = 167) secretion in a US birth cohort.
      RESULTS: Higher levels of n-6 linoleic acid were correlated with higher IL-13
      levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P =
      .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced
      lymphocyte proliferation and IFN-gamma levels in response to Bla g 2 and Der f 1
      stimulation. Controlling for potential confounders, EPA and AA had similar
      independent effects on reduced allergen-stimulated IFN-gamma levels. If neonates
      had either EPA or AA levels in the highest quartile, their Der f 1 IFN-gamma
      levels were 90% lower (P = .0001) than those with both EPA and AA levels in the
      lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen
      stimulated IFN-gamma level. CONCLUSION: Increased levels of fetal n-3 EPA and n-6
      AA might have similar effects on attenuation of cord blood lymphocyte
      proliferation and IFN-gamma secretion. CLINICAL IMPLICATIONS: The implications of
      these findings for allergy or asthma development are not yet known.

PMID- 16630955
TI  - IgE memory: persistence of antigen-specific IgE responses years after treatment
      of human filarial infections.
AB  - BACKGROUND: The human immune response to helminth infections is characterized by
      elevated serum levels of antigen-specific IgE. Although it is well established
      that IgG humoral immunity can persist for years, as yet there have been no
      longitudinal studies of antigen-specific IgE responses to helminth infection in
      the absence of re-exposure to pathogen. OBJECTIVE: We sought to determine the
      presence of filaria-specific IgE responses years after treatment of human
      filarial infections in patients no longer living in a region endemic for
      filariasis. METHODS: Filaria-specific IgE levels were measured in 34 filaria
      infected patients before and 11 to 178 (median = 33) months after anthelmintic
      therapy. Frequencies of filaria-specific IgE-producing cells and measures of
      filaria-specific IgE-mediated histamine and IL-4 release from basophils were
      measured in subsets of these patients. RESULTS: At follow-up, all patients were
      asymptomatic without evidence of active infection, and none had traveled to
      filaria-endemic regions since initial evaluation. Although frequencies of Brugia
      malayi antigen (BmAg)-specific IgE-producing cells and serum levels of BmAg
      specific IgE decreased significantly over time, both remained detectable in the
      majority of patients years after initial treatment. Six of 10 patients' basophils
      released histamine in response to BmAg after treatment (vs 7 of 10 before
      treatment). Basophils also continued to release IL-4 after stimulation with BmAg
      years after treatment. CONCLUSION: These results demonstrate that filaria
      specific IgE production and filaria-specific IgE-mediated basophil release of
      histamine and IL-4 persist for years after treatment of human filarial
      infections. CLINICAL IMPLICATIONS: These findings suggest that (1) absolute
      allergen avoidance may not result in the loss of allergy, and (2) parasite
      specific IgE-inducing vaccines, if effective, could potentially induce
      longstanding protection.

PMID- 16630956
TI  - Quantitative assessment of the compliance with a once-daily sublingual
      immunotherapy regimen in real life (EASY Project: Evaluation of A novel SLIT
      formulation during a Year).

PMID- 16630957
TI  - Airway inflammation in occupational asthma caused by styrene.

PMID- 16630958
TI  - Prolonged elevation of serum tryptase in idiopathic anaphylaxis.

PMID- 16630959
TI  - Deep inhalation bronchoprotection in asthma: correlation with airway
      responsiveness.

PMID- 16630960
TI  - Nutritional supplements and pediatric upper respiratory tract illnesses.

PMID- 16630962
TI  - Cost-effectiveness of home-based interventions should also take into account
      nonrespiratory indoor health hazards.

PMID- 16630965
TI  - The difference between groups and individuals.

PMID- 16630966
TI  - Viral specimen collection by parents increases response rate in population-based
      virus studies.

PMID- 16630968
TI  - Environment-induced reactivity against autoallergens: possible role of latex.

PMID- 16630970
TI  - An examination of covert observation and solution audit as tools to measure the
      success of hand hygiene interventions.
AB  - BACKGROUND: Many studies have examined hand hygiene (HH) frequency and adherence
      in response to various interventions. This study used 2 methods to determine HH
      frequency and adherence to see how well the outcomes correlated. METHODS: HH
      frequency was measured over 4, 1-month periods (phases 1-4), using 2 methods: an
      audit of HH solution used during each phase adjusted for patient-days and covert
      observation of HH adherence. The number of x-ray technician contacts with
      patients (a known quantity) across the study period was retrospectively compared
      with the number of observations made of x-ray technicians' HH behavior to see
      what proportion of contacts were observed. RESULTS: HH solution use doubled in
      phase 2 and was 65% and 55% higher than the baseline level in phases 3 and 4,
      respectively. Observed HH adherence fell from 51% to 37% in phase 2 and then rose
      to 58% in phases 3 and 4. Three percent of x-ray technicians' patient contacts
      were observed across the 4 phases. CONCLUSION: Observation of HH may not
      adequately sample patient contacts to provide an accurate measure of HH
      adherence. Further studies are needed to confirm this finding.

PMID- 16630971
TI  - Factors associated with personal protection equipment use and hand hygiene among
      hemodialysis staff.
AB  - BACKGROUND: Because exposure to blood by health care workers is frequent during
      hemodialysis, gloves are required for all contact with patients and their
      equipment, followed by hand hygiene. In this study, we investigated factors
      associated with performing these practices as recommended. METHODS: Staff members
      from a sample of 45 US hemodialysis facilities were surveyed using an anonymous
      self-administered questionnaire. Factors independently associated with reporting
      increased compliance with recommended hand hygiene and glove use practices during
      patient care were identified with multivariate modeling. RESULTS: Of 605 eligible
      staff members, 420 (69%) responded: registered nurses, 41%; dialysis technicians,
      51%; and licensed practical nurses, 8%. Only 35% reported that dialysis patients
      were at risk for bloodborne virus infections, and only 36% reported always
      following recommended hand hygiene and glove use practices. Independent factors
      associated with more frequent compliance were being a technician (versus a
      registered nurse) and reporting always doing what was needed to protect
      themselves from infection. CONCLUSION: Compliance with recommended hand hygiene
      and glove use practices by hemodialysis staff was low. The rationale for
      infection control practices specific to the hemodialysis setting was poorly
      understood by all staff. Infection control training should be tailored to this
      setting and should address misconceptions.

PMID- 16630972
TI  - Consideration of age at admission for selective screening to identify methicillin
      resistant Staphylococcus aureus carriers to control dissemination in a medical
      ward.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become an
      increasingly important pathogen responsible for hospital-acquired infections. Our
      study was to evaluate the efficiency of our selective screening program for
      methicillin-resistant Staphylococcus aureus (MRSA) carriers at admission to
      nonintensive care units. METHODS: During 6 months, all patients were screened at
      admission to an internal medicine ward, at which time they were classified as
      patients at risk of carriage (PRC) and those with no known risk factor. The
      amplitude of cross transmission was estimated using various indicators during
      this universal screening period and during the same calendar period of the
      preceding year (selective screening). RESULTS: The prevalence of MRSA carriage at
      admission was 5.5%. Among the 22 carriers identified, only 10 were PRC. Age >80
      years was significantly associated with MRSA carriage upon admission (OR, 3.5; P
      < .01). All estimation indicators of MRSA dissemination amplitude were
      significantly lower during universal screening (relative risks varied from 2.79
      to 26.4 according to indicators), demonstrating the need to broaden our criteria
      defining PRC. CONCLUSION: Adding patients >80 years of age to our PRC definition
      would increase screening sensitivity (15 carriers identified for 128 patients
      sampled) and would enable early implementation of barrier precautions for the
      additional carriers identified.

PMID- 16630973
TI  - Gender risk differences for surgical site infections among a primary coronary
      artery bypass graft surgery cohort: 1995-1998.
AB  - BACKGROUND: Knowledge about gender risk factors associated with acquiring
      postoperative coronary artery bypass graft (CABG) surgical site infections (SSIs)
      is limited. OBJECTIVE: Our objective was to determine whether the incidence of
      SSIs during 30 days postsurgery was greater among females compared with males who
      undergo primary (first time) CABG. METHODS: A retrospective cohort study of 3878
      patients who had primary CABG surgery between January 1, 1995, and December 31,
      1998, at a cardiovascular center in the American Southwest. Multivariate
      techniques were used to analyze outcome risk differences by gender. RESULTS: The
      nosocomial SSI incidence rate among 957 females was 10.56%; among 2921 males, it
      was 7.57%; relative risk (RR) was 1.39 (95% confidence interval: 1.12-1.75), and
      Mantel-Haenszel chi2 test was 8.47 (P = .004). Four preoperative variables were
      independent predictors of acquiring SSI: female gender, diabetes, body mass
      index, and urgency of surgery. CONCLUSION: Females were at greater risk for
      acquiring SSIs postprimary CABG surgery in this cohort. Also, preoperative,
      perioperative, and postoperative control of glucose levels in diabetics and
      preoperative reduction of weight in obese patients may help to reduce SSIs post
      CABG surgery. More studies are needed to understand gender-associated risk of SSI
      after CABG surgery.

PMID- 16630974
TI  - Infection control program disparities between acute and long-term care facilities
      in Maryland.
AB  - BACKGROUND: In January 2003, the Maryland State Department of Health and Mental
      Hygiene (DHMH) surveyed, for the first time, all acute care hospitals (ACHs),
      long-term care facilities (LTCFs), and specialty hospital (acute rehabilitation
      and behavioral health) facilities in the state to determine the current state of
      infection control resources and practices in Maryland. Federal health care
      facilities in Maryland were not surveyed. METHODS: A self-administered
      questionnaire was sent to all 40 ACHs, 247 LTCFs, and 20 specialty hospitals in
      the state. The senior infection control professional (ICP) in the facility
      completed the questionnaire. RESULTS: The response rates were 85% for ACHs, 39%
      for LTCFs, and 95% for specialty hospitals. Data were analyzed separately for
      each type of facility. The ICPs in acute care reported 1.2 full-time equivalent
      positions (FTEs) for each 200 acute care beds, whereas ICPs in LTCFs reported 0.3
      FTEs per 200 LTCF beds. Ninety percent of acute care ICPs reported taking some
      type of basic infection control course, whereas only 3% of long-term care ICPs
      reported taking a basic infection control course. CONCLUSION: In this survey of
      ICPs in Maryland, striking differences were noted between ACHs and LTCFs in the
      ratio of ICP FTEs to beds and in basic infection control educational preparation
      for ICPs. These findings suggest that Maryland LTCFs could benefit from basic
      infection control training and from regulatory actions addressing staff-to
      resident ratios.

PMID- 16630975
TI  - Bacterial contamination of nonsterile disposable gloves before use.
AB  - BACKGROUND: After Bacillus cereus recovery in opened boxes of disposable gloves,
      the bacteriological contamination of disposable nonsterile gloves kept stored in
      native packages was investigated prospectively. METHODS: Thirty-six commercially
      available nonsterile nonpowdered disposable gloves made of latex, vinyl, or
      nitrile were cultured. RESULTS: A large variety of spore-forming and non-spore
      forming bacteria was recovered, including Bacillus cereus and Clostridium
      perfringens. CONCLUSION: This finding must be taken into consideration for care
      involving gloves in very immunocompromised patients.

PMID- 16630976
TI  - Enteral tube hub as a reservoir for transmissible enteric bacteria.
AB  - Enteral feeding is a risk factor for cross transmission of microbes.
      Administration set tubing can be colonized by organisms present in the enteral
      tube hub; molecular typing has demonstrated genetic relatedness of enteric
      bacteria isolated from both sites. Strict attention to infection control measures
      is imperative when handling enteral feed apparatuses.

PMID- 16630977
TI  - Results of the Spanish national nosocomial infection surveillance network
      (VICONOS) for surgery patients from January 1997 through December 2003.
AB  - BACKGROUND: In 1997, a national standardized surveillance system for nosocomial
      infections (NI) in surgery patients was established in Spain. This system, known
      as the VICONOS program, is based on the US National Nosocomial Infection
      Surveillance System (NNISS). Herein, we present a summary of the data collected
      from January 1997 to December 2003. METHODS: VICONOS actively monitors all
      patients referred to the surgery ward of each participating hospital. The
      criteria used to define surgical site infection (SSI), patient risk index
      category, and surgical procedures used are those established by the Centers for
      Disease Control and Prevention (CDC) and the NNISS. RESULTS: SSI rates are shown
      by operative procedure and NNISS risk index category. Standardized infection
      ratios (SIR) were calculated for the 7 surgical procedures most frequently
      performed to compare our rates with those published by the NNISS. We provide
      factors that can be used as quality indicators such as rates of main surgery
      complications, length of hospital stay, and presurgery prophylaxis. Also
      described are the most used antimicrobial agents, the microorganisms most
      frequently isolated, and the corresponding sites. CONCLUSION: VICONOS counts on
      the voluntary participation of 43 Spanish public hospitals. Our immediate plans
      are to incorporate new surveillance components and encourage new centers to join
      our network.

PMID- 16630978
TI  - Ensuring rational public reporting systems for health care-associated infections:
      systematic literature review and evaluation recommendations.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) systematically
      reviewed published studies for the Healthcare Infection Control Practices
      Advisory Committee (HICPAC) in preparation for guidance to states on mandatory
      public reporting systems for health care-associated infections (HAI) in
      hospitals. The HICPAC asked whether public reporting systems are effective in
      improving health care performance, by measured improvements in clinical processes
      or patients' health status as the intended outcomes, including but not limited to
      reduced HAI events; and whether new evidence of effectiveness of private
      reporting policies to reduce HAI had been published since the 1970s landmark
      Study on the Efficacy of Nosocomial Infection Control study. METHODS: Public
      reporting systems are information provided to the public about the quality of
      health services. Of 450 published papers reviewed using specific inclusion and
      exclusion criteria, 10 studies qualified for detailed, protocol-based
      abstractions. RESULTS: Findings indicate that the evidence for effectiveness for
      public reporting systems to improve health care performance is inconclusive. No
      studies have investigated reduction of HAI as an outcome of public reporting.
      CONCLUSION: Rigorous evaluation of mandatory public reporting systems for HAI is
      recommended to ensure that stakeholders' needs are identified and met.

PMID- 16630979
TI  - Alcohol-based hand sanitizer: can frequent use cause an elevated blood alcohol
      level?

PMID- 16630980
TI  - Prepackaged hand hygiene educational tools facilitate implementation.
AB  - The Healthcare Infection Control Practices Advisory Committee released hand
      hygiene guidelines recommending that hospitals educate personnel to increase
      compliance with hand hygiene. However, few educational tools are available to
      assist hospitals in this effort. Eight hospitals were recruited to implement hand
      hygiene educational tools. Key informant interviews were conducted with infection
      control professionals (ICPs) at 5 participating hospitals. Lack of personnel time
      was the primary barrier to implementing the educational tools. Multimodal,
      prepackaged educational tools are needed to decrease barriers and facilitate
      implementation of interventions locally by ICPs.

PMID- 16630981
TI  - The role of chiropractic adjusting tables as reservoirs for microbial diseases.
AB  - BACKGROUND: Our goal was to enumerate the microbial flora on the headrest,
      armrest, and thoracic portion of chiropractic adjusting tables to determine the
      presence of pathogenic microorganisms and identify the potential for nosocomial
      transmission. METHODS: Defined portions of the headrest, armrest, and
      thoracoabdominal pieces from 9 chiropractic adjusting tables were randomly
      sampled using the ACT II culture transport system (Remel, Lenexa, KS). Samples
      were incubated using standard culture techniques for bacteriology and mycology
      that included 15 mL of heart infusion agar at 35 degrees C for 24 hours and 15 mL
      of Sabouraud dextrose agar at 30 degrees C up to 7 days. RESULTS: Identification
      of microorganisms by biochemical analysis yielded a wide variety of gram-positive
      (G+) and gram-negative (G-) cocci and bacilli as well as standard fungi. Many
      were of the genus Staphylococcus. Methicillin-resistant S. aureus (MRSA) isolates
      were recovered from 2 separate tables. CONCLUSION: This study supports a growing
      consensus that those outpatient facilities that do not adhere to strict infection
      control protocols may become ecological reservoirs of potentially harmful human
      pathogens.

PMID- 16630982
TI  - HTLV-II transmission to a health care worker.
AB  - Health care workers, mainly in emergency and forensic services, are at risk of
      exposure to bloodborne pathogens. Human T-cell lymphotropic virus type I and type
      II (HTLV-I and HTLV-II) are cosmopolitan human delta retroviruses causing endemic
      infection in Japan, the Caribbean basin, South America, and sub-Saharan Africa,
      and in clusters among intravenous drug users in Europe and the United States. The
      seroprevalence of HTLV-I and HTLV-II among Brazilian blood donors ranges from
      0.08% to 1.35%. HTLV-I transmission to a Japanese researcher has already been
      reported. We describe the transmission of HTLV-II infection to a Brazilian
      laboratory worker caused by a needlestick injury when she was recapping a syringe
      after collecting material for arterial blood gas analysis. To our knowledge, this
      is the first report of an occupational transmission of HTLV-II to a health care
      worker.

PMID- 16630983
TI  - Underdiagnosis of hospital-acquired Legionnaires disease in Singapore.

PMID- 16630984
TI  - Implantable cardioverter-defibrillator therapy in clinical practice.
AB  - Pharmacologic treatment of heart failure has led to dramatic improvements in
      survival and quality of life. Nonetheless, heart failure often progresses despite
      treatment with diuretics, angiotensin-converting enzyme inhibitors, beta
      adrenergic blockers, aldosterone antagonists, and digoxin. Further, despite a
      steady decline in the risk of death from pump failure, many patients remain at
      high risk for sudden cardiac death. The annual incidence of sudden cardiac death
      in the U.S. alone has been estimated at 184,000 to over 400,000 cases. During the
      past decade, substantial advances have been made in the use of device-based
      therapy for this population. The role of the implantable cardioverter
      defibrillator (ICD) continues to evolve in routine heart failure management. The
      current status of ICD therapy in the treatment of heart failure patients based on
      randomized clinical trial results and published practice guidelines is summarized
      in this review.

PMID- 16630985
TI  - An outline for public registration of clinical trials evaluating medical devices.
AB  - Public registration of clinical trials is fundamentally important to the
      integrity of the medical device development process. In addition to fulfilling
      obligations to those study volunteers, a complete record of trial results
      provides the general public, clinical community, and medical device manufacturers
      with a more accurate understanding as to how a specific therapeutic should be
      used. Although the issues associated with public disclosure of clinical trials
      are similar to the pharmaceutical industries, the iterative nature of device
      development introduces differences in what type of information needs to be
      disclosed during development and commercialization. The Second Dartmouth Device
      Development Symposium (3D2) held in October 2004 brought together thought leaders
      representing many of the stakeholders associated with medical device development.
      This consensus document arising from the proceedings of the 3D2 is offered to
      provide background to these issues and recommend pathways to implementation of
      device trial registration.

PMID- 16630986
TI  - Oral rapamycin after coronary bare-metal stent implantation to prevent
      restenosis: the Prospective, Randomized Oral Rapamycin in Argentina (ORAR II)
      Study.
AB  - OBJECTIVES: The purpose of this study was to assess the role of oral rapamycin in
      decreased restenosis after bare metal stent implantation. BACKGROUND: Small
      observational studies suggest that the administration of oral rapamycin reduces
      angiographic restenosis after bare metal stent implantation. METHODS: Between
      September 2003 and September 2004, 100 patients were randomized to either oral
      rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day
      for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a
      coronary bare metal stent design. The primary study end point was incidence of
      angiographic binary restenosis and late loss at nine months. The secondary end
      points were target lesion revascularization, target vessel revascularization, and
      incidence of major adverse cardiovascular events at 1 year. RESULTS: Angiographic
      follow-up was completed in 87% of patients. In the rapamycin group, the drug was
      well tolerated (26% minor side effects) and was maintained in 96% of patients. At
      9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin
      vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was
      reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in
      segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13
      mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral
      rapamycin group also showed a significantly lower incidence of target vessel
      revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion
      revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse
      cardiovascular events (20% vs. 44%, respectively, p = 0.018). CONCLUSIONS: This
      randomized, controlled, and unblinded study showed that the administration of
      oral rapamycin during 14 days after stent implantation significantly reduces
      angiographic and clinical parameters of restenosis.

PMID- 16630987
TI  - Distal left main coronary disease is a major predictor of outcome in patients
      undergoing percutaneous intervention in the drug-eluting stent era: an integrated
      clinical and angiographic analysis based on the Rapamycin-Eluting Stent Evaluated
      At Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated At
      Rotterdam Cardiology Hospital (T-SEARCH) registries.
AB  - OBJECTIVES: This study sought to investigate whether the anatomical location of
      the disease carries prognostic implications in patients undergoing drug-eluting
      stent (DES) implantation for the left main coronary artery (LMCA) stenosis.
      BACKGROUND: Liberal use of DES, compared with a bare metal stent (BMS), has
      resulted in an improved outcome in patients undergoing LMCA intervention.
      However, the overall event rate in this subset of patients remains high, and
      alternative tools to risk-stratify this population beyond conventional surgical
      risk status would be desirable. METHODS: From April 2002 to June 2004, 130
      patients received DES as part of the percutaneous intervention for LMCA stenoses
      in our institution. Distal LMCA disease (DLMD) was present in 94 patients. They
      were at higher surgical risk and presented with a greater coronary disease extent
      compared with patients without DLMD. RESULTS: After a median of 587 days (range
      368 to 1,179 days), the cumulative incidence of major adverse cardiac events
      (MACE) was significantly higher in patients with DLMD at 30% versus 11% in those
      without DLMD (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.34 to 9.7; p
      = 0.007), mainly driven by the different rate of target vessel revascularization
      (13% and 3%; HR 6, 95% CI 1.2 to 29; p = 0.02). After adjustment for confounders,
      DLMD (HR 2.79,95% CI 1.17 to 8.9; p = 0.032) and surgical risk status (HR
      2.18,95% CI 1.06 to 4.5; p = 0.038) remained independent and complementary
      predictors of MACE. CONCLUSIONS: Distal LMCA disease carries independent
      prognostic implications, and it may help in selecting the most appropriate
      patient subset for LMCA intervention beyond the conventional surgical risk status
      in the DES era.

PMID- 16630988
TI  - Rate, predictors, and consequences of hemodynamic depression after carotid artery
      stenting.
AB  - OBJECTIVES: We sought to determine the frequency, predictors, and consequences of
      hemodynamic depression (HD) after carotid artery stenting (CAS). BACKGROUND:
      Hemodynamic depression has been reported after carotid artery stenting CAS and
      carotid endarterectomy (CEA). METHODS: We retrospectively analyzed data on 500
      consecutive CAS procedures performed over a 5-year period. Hemodynamic depression
      was defined as periprocedural hypotension (systolic blood pressure <90 mm Hg) or
      bradycardia (heart rate <60 beats/s). Univariate and multivariate binary logistic
      regression models were used to determine the predictors and consequences of HD
      and persistent HD. RESULTS: The mean age of the patients was 70.5 +/- 10 years,
      and 69% were men. Hemodynamic depression occurred during 210 procedures (42%),
      whereas persistent HD developed in 84 procedures (17%). Features that
      independently predicted HD included lesions involving the carotid bulb (odds
      ratio [OR] 2.18 [range 1.46 to 3.26], p < 0.0001) or the presence of a calcified
      plaque (OR 1.89 [range 1.25 to 2.84], p < 0.002). Prior ipsilateral CEA was
      associated with reduced risk of HD (OR 0.35 [range 0.20 to 0.60], p < 0.0001).
      Patients who developed persistent HD were at a significantly increased risk of a
      periprocedural major adverse clinical event (OR 3.05 [range 1.35 to 5.23], p <
      0.02) or stroke (OR 3.34 [range 1.13 to 9.90], p < 0.03). CONCLUSIONS:
      Hemodynamic depression is common after CAS, particularly in patients with a
      calcified plaque in the carotid bulb, but is easily treated with conventional
      methods. Patients who develop persistent HD are at an increased risk of
      periprocedural major adverse clinical events and stroke.

PMID- 16630989
TI  - The pre-hospital electrocardiogram and time to reperfusion in patients with acute
      myocardial infarction, 2000-2002: findings from the National Registry of
      Myocardial Infarction-4.
AB  - OBJECTIVES: The aim of this study was to determine the use of pre-hospital
      electrocardiogram (ECG) in patients with ST-segment elevation myocardial
      infarction (STEMI) undergoing reperfusion therapy, and evaluate the effect of pre
      hospital ECG on door-to-reperfusion times. BACKGROUND: Although national
      guidelines recommend the use of pre-hospital ECG, there is limited contemporary
      information about its current use and effectiveness. METHODS: Using data from the
      National Registry of Myocardial Infarction-4, we studied patients with STEMI or
      left bundle branch block who received acute reperfusion with either fibrinolytic
      therapy (n = 35,370) or primary percutaneous coronary intervention (PCI) (n =
      21,277) within 6 h of admission. We determined the prevalence of pre-hospital ECG
      use, evaluated the association between pre-hospital ECG and door-to-reperfusion
      time, and estimated the incremental reduction in time to reperfusion using
      hierarchical models to adjust for differences in patient and hospital
      characteristics. RESULTS: A pre-hospital ECG was performed in 4.5% of the
      fibrinolytic therapy cohort and in 8.0% of the PCI cohort. After adjusting for
      patient and hospital characteristics, the use of pre-hospital ECG was associated
      with a significantly shorter geometric mean door-to-drug time: 24.6 min (95%
      confidence interval [CI]: 23.7 to 25.5) vs. 34.7 min (95% CI: 34.2 to 35.3; p <
      0.0001), and a significantly shorter geometric mean door-to-balloon time (94.0
      min [95% CI: 91.8 to 96.3] vs. 110.3 min [95% CI: 108.7 to 112.0]; p < 0.0001).
      CONCLUSIONS: The national use of pre-hospital ECG to diagnose and facilitate the
      treatment of STEMI remains low. When used, however, pre-hospital ECG is
      associated with a significantly shorter time to reperfusion.

PMID- 16630990
TI  - Application of the Thrombolysis in Myocardial Infarction risk index in non-ST
      segment elevation myocardial infarction: evaluation of patients in the National
      Registry of Myocardial Infarction.
AB  - OBJECTIVES: The purpose of this research was to evaluate the Thrombolysis In
      Myocardial Infarction risk index (TRI) to characterize the risk of death among
      patients with non-ST-segment elevation myocardial infarction (NSTEMI).
      BACKGROUND: The TRI, calculated from baseline age, systolic pressure, and heart
      rate, was established in patients with ST-segment elevation myocardial infarction
      (STEMI) and is predictive of mortality. Patients presenting with NSTEMI are
      increasing compared to STEMI and constitute a group with varied risk. METHODS:
      The TRI was calculated in 337,192 patients from the National Registry of
      Myocardial Infarction with NSTEMI. Values and outcomes were compared with 153,486
      patients with STEMI classified by reperfusion status. Comparisons of baseline
      characteristics and clinical outcomes stratified by TRI were made. RESULTS: There
      was a graded relationship between the TRI and mortality in patients with NSTEMI
      with a >30-fold difference in mortality rates between lowest and highest deciles
      (p < 0.0001). The index showed good discrimination (c = 0.73). Overall mortality
      in the group with NSTEMI was higher (10.9%) than patients with STEMI treated with
      (6.6%) but lower than for STEMI patients not receiving reperfusion therapy
      (18.7%). The higher risk in comparison to patients with STEMI treated with
      reperfusion therapy was explained largely by the higher-risk profile of the
      population with NSTEMI. CONCLUSIONS: There is a graded relationship between TRI
      and mortality in patients with NSTEMI. This simple risk index provides important
      information about mortality in patients across the spectrum of myocardial
      infarction, STEMI and NSTEMI. Early identification of NSTEMI patients who are at
      high risk of in-hospital mortality may provide clinicians with important
      information for initial triage and treatment.

PMID- 16630991
TI  - Cardiac expression of placental growth factor predicts the improvement of chronic
      phase left ventricular function in patients with acute myocardial infarction.
AB  - OBJECTIVES: Our aim was to investigate cardiac expression of placental growth
      factor (PlGF) and its clinical significance in patients with acute myocardial
      infarction (AMI). BACKGROUND: Placental growth factor is known to stimulate wound
      healing by activating mononuclear cells and inducing angiogenesis. The clinical
      significance of PlGF in AMI is not yet known. METHODS: Fifty-five AMI patients
      and 43 control subjects participated in the study. Peripheral blood sampling was
      performed on days 1, 3, and 7 after AMI. Blood was also sampled from the coronary
      artery (CAos) and the coronary sinus (CS), before and after acute coronary
      recanalization. Cardiac expression of PlGF was analyzed in a mouse AMI model.
      RESULTS: In AMI patients, peripheral plasma PlGF levels on day 3 were
      significantly higher than in control subjects. Plasma PlGF levels just after
      recanalization were significantly higher in the CS than the CAos, which indicates
      cardiac production and release of PlGF. Peripheral plasma levels of PlGF on day 3
      were negatively correlated with the acute phase left ventricular ejection
      fraction (LVEF), positively correlated with both acute phase peak peripheral
      monocyte counts and chronic phase changes in LVEF. Placental growth factor
      messenger ribonucleic acid expression was 26.6-fold greater in a mouse AMI model
      than in sham-operated mice, and PlGF was expressed mainly in endothelial cells
      within the infarct region. CONCLUSIONS: Placental growth factor is rapidly
      produced in infarct myocardium, especially by endothelial cells during the acute
      phase of myocardial infarction. Placental growth factor might be over-expressed
      to compensate the acute ischemic damage, and appears to then act to improve LVEF
      during the chronic phase.

PMID- 16630992
TI  - A common polymorphism in the complement factor H gene is associated with
      increased risk of myocardial infarction: the Rotterdam Study.
AB  - OBJECTIVES: This study was designed to investigate the association between a
      common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene
      and risk of coronary heart disease. BACKGROUND: The evidence that inflammation is
      an important mechanism in atherogenesis is growing. C-reactive protein (CRP),
      complement factors, and complement regulatory factors have all been linked to
      coronary heart disease. The CFH gene is an important regulator of the alternative
      complement cascade. We investigated its association with coronary heart disease.
      METHODS: The study was embedded in the Rotterdam Study, a prospective population
      based study among men and women aged 55 years and over. A total of 5,520
      participants without history of coronary heart disease was genotyped for the
      Tyr402His polymorphism of the CFH gene. Cox proportional hazards analysis was
      used to determine risk of myocardial infarction for Tyr402His genotypes. RESULTS:
      Mean age among participants was 69.5 years (SD 9.1 years). The overall frequency
      of the His allele was 36%; genotype frequencies were 41%, 45%, and 14% for
      TyrTyr, TyrHis, and HisHis, respectively. During a mean follow-up period of 8.4
      years, 226 myocardial infarctions occurred. After adjustment for age, gender,
      established cardiovascular risk factors, and CRP level, HisHis homozygotes had a
      hazard ratio of 1.77 (95% confidence interval 1.23 to 2.55) for myocardial
      infarction. Total cholesterol level, diabetes mellitus, and smoking modified the
      effect. The Tyr402His polymorphism was not associated with established
      cardiovascular risk factors or CRP level. CONCLUSIONS: Our data suggest that the
      CFH gene determines susceptibility to myocardial infarction. This finding
      underscores the importance of the alternative complement system in cardiovascular
      disease.

PMID- 16630993
TI  - Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved
      left ventricular systolic function: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVES: This study sought to assess the efficacy of angiotensin-converting
      enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved
      left ventricular (LV) function. BACKGROUND: The ACEIs have been shown to improve
      outcomes in patients with heart failure and myocardial infarction (MI). However,
      there is conflicting evidence concerning the benefits of ACEIs in patients with
      coronary artery disease (CAD) and preserved LV systolic function. METHODS: An
      extensive search was performed to identify randomized, placebo-controlled trials
      of ACEI use in patients with CAD and preserved LV systolic function. Of 61
      potentially relevant articles screened, 6 trials met the inclusion criteria. They
      were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause
      mortality, and revascularization rates. We performed random-effect model meta
      analyses and quantified between-studies heterogeneity with I(2). RESULTS: There
      were 16,772 patients randomized to ACEI and 16,728 patients randomized to
      placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality
      (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01),
      nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR
      0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95%
      CI 0.87 to 1.00, p = 0.04). There was no significant between-studies
      heterogeneity. Treatment of 100 patients for an average duration of 4.4 years
      prevents either of the adverse outcomes (one death, or one nonfatal myocardial
      infarction, or one cardiovascular death or one coronary revascularization
      procedure). CONCLUSIONS: The cumulative evidence provided by this meta-analysis
      shows a modest favorable effect of ACEIs on the outcome of patients with CAD and
      preserved LV systolic function.

PMID- 16630994
TI  - Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe
      in patients with mixed hyperlipidemia.
AB  - OBJECTIVES: This study sought to determine the long-term safety and efficacy of
      co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed
      hyperlipidemia. BACKGROUND: Both EZE and FENO offer complementary benefits to the
      lipid profile of patients with mixed hyperlipidemia. METHODS: After completing
      the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160
      mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed
      hyperlipidemia, patients continued into a double-blind, 48-week extension phase.
      Those patients in the FENO plus EZE and FENO groups continued on their respective
      base study treatment, and patients in the EZE and placebo groups were switched to
      FENO plus EZE and FENO, respectively. RESULTS: Of the 587 patients who completed
      the base study, 576 continued into the extension study (n = 340 in FENO plus EZE
      and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions
      in low-density lipoprotein-cholesterol compared with FENO (-22% vs. -9%,
      respectively; p < 0.001). There were also significantly greater improvements in
      triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol,
      non-HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in
      apolipoprotein A-I and high-sensitivity C-reactive protein were similar between
      groups. Overall, FENO plus EZE was well tolerated during the extension study. The
      proportion of patients with consecutive elevations of alanine
      aminotransferase/aspartate aminotransferase > or =3 times upper limit of normal
      were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of
      creatine phosphokinase elevations > or =10 times upper limit of normal or
      myopathy were observed in either group. CONCLUSIONS: Long-term, 48-week co
      administration of FENO plus EZE was well tolerated and more efficacious than FENO
      in patients with mixed hyperlipidemia.

PMID- 16630995
TI  - Prevalence of the metabolic syndrome and its relation to cardiovascular disease
      in an elderly Chinese population.
AB  - OBJECTIVES: This study sought to assess the prevalence of the metabolic syndrome
      (MetS) and its association with cardiovascular disease (CVD) in elderly Chinese
      people. BACKGROUND: The information available about the prevalence of MetS based
      on the National Cholesterol Education Program (NCEP) and the International
      Diabetes Federation (IDF) in China is limited. METHODS: We conducted a population
      based cross-sectional study in an urban Beijing sample of 2,334 participants age
      60 to 95 years (943 men, 1,391 women). The CVD included diagnosed coronary heart
      disease (CHD), stroke, and peripheral arterial disease (PAD). RESULTS: The
      prevalence of MetS by the NCEP criteria was 30.5% (17.6% in men, 39.2% in women).
      Use of the new IDF definition significantly increased the prevalence to 46.3%
      (34.8% in men, 54.1% in women). Odds ratios (OR) for CHD, stroke, PAD, and CVD in
      those with MetS using the NCEP criteria were 1.43 (95% confidence interval [CI]
      1.18 to 1.74), 1.45 (95% CI 1.14 to 1.85), 1.47 (95% CI 1.18 to 1.84), and 1.50
      (95% CI 1.25 to 1.81), respectively. Corresponding ORs using new IDF criteria
      were 1.69 (95% CI 1.40 to 2.02), 1.58 (95% CI 1.26 to 2.00), 1.42 (95% CI 1.14 to
      1.76), and 1.73 (95% CI 1.46 to 2.07), respectively. Those who met the IDF but
      not the NCEP criteria (n = 436, 18.7%) had significantly elevated ORs for CHD
      (1.66, 95% CI 1.31 to 2.10) and stroke (1.53, 95% CI 1.13 to 2.06). CONCLUSIONS:
      The MetS is highly prevalent in elderly people in Beijing, particularly among
      women. Individuals with MetS defined by either criteria are at significantly
      elevated ORs for CHD, stroke, and PAD. The IDF criteria seem to be better suited
      than the NCEP criteria for screening and estimating risk of MetS in Chinese
      people.

PMID- 16630996
TI  - Metabolic syndrome and the risk of cardiovascular disease in older adults.
AB  - OBJECTIVES: The purpose of this study was to assess whether metabolic syndrome
      (MetSyn) predicts a higher risk for cardiovascular events in older adults.
      BACKGROUND: The importance of MetSyn as a risk factor has not previously focused
      on older adults and deserves further study. METHODS: We studied the impact of
      MetSyn (38% prevalence) on outcomes in 3,035 participants in the Health, Aging,
      and Body Composition (Health ABC) study (51% women, 42% black, ages 70 to 79
      years). RESULTS: During a 6-year follow-up, there were 434 deaths overall, 472
      coronary events (CE), 213 myocardial infarctions (MI), and 231 heart failure (HF)
      hospital stays; 59% of the subjects had at least one hospital stay. Coronary
      events, MI, HF, and overall hospital stays occurred significantly more in
      subjects with MetSyn (19.9% vs. 12.9% for CE, 9.1% vs. 5.7% for MI, 10.0% vs.
      6.1% for HF, and 63.1% vs. 56.1% for overall hospital stay; all p < 0.001). No
      significant differences in overall mortality was seen; however, there was a trend
      toward higher cardiovascular mortality (5.1% vs. 3.8%, p = 0.067) and coronary
      mortality (4.5% vs. 3.2%, p = 0.051) in patients with MetSyn. After adjusting for
      baseline characteristics, patients with MetSyn were at a significantly higher
      risk for CE (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.28 to 1.91),
      MI (HR 1.51, 95% CI 1.12 to 2.05), and HF hospital stay (HR 1.49, 95% CI 1.10 to
      2.00). Women and whites with MetSyn had a higher coronary mortality rate. The CE
      rate was higher among subjects with diabetes and with MetSyn; those with both had
      the highest risk. CONCLUSIONS: Overall, subjects over 70 years are at high risk
      for cardiovascular events; MetSyn in this group is associated with a
      significantly greater risk.

PMID- 16630997
TI  - A comparison of the effects of carvedilol and metoprolol on well-being,
      morbidity, and mortality (the "patient journey") in patients with heart failure:
      a report from the Carvedilol Or Metoprolol European Trial (COMET).
AB  - OBJECTIVES: This study was designed to investigate the loss of well-being, in
      terms of life-years, overall and in patients randomized to metoprolol versus
      carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND:
      The ultimate objectives of treating patients with heart failure are to relieve
      suffering and prolong life. Although the effect of treatment on mortality is
      usually described in trials, the effects on patient well-being throughout the
      trials' courses are rarely reported. METHODS: A total of 3,029 patients
      randomized in the COMET study were included in the analysis. "Patient journey"
      was calculated by adjusting days alive and out of hospital over four years using
      a five-point score completed by the patient every four months, adjusted according
      to the need for intensification of diuretic therapy. Scores ranged from 0% (dead
      or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all
      days were lost through death, 1% through hospitalization, 23% through impaired
      well-being, and 2% through the need for intensified therapy. Compared with
      metoprolol, carvedilol was associated with fewer days lost to death, with no
      increase in days lost due to impaired well-being or days in hospital. The
      "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD
      26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart
      failure remains associated with a marked reduction in well-being and survival.
      Loss of quality-adjusted life-years through death and poor well-being seemed of
      similar magnitude over four years, and both were much larger than the loss that
      could be attributed to hospitalization.

PMID- 16630998
TI  - Mapping the journey.

PMID- 16630999
TI  - Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor
      vasopressin antagonist, in New York Heart Association functional class II and III
      chronic heart failure patients.
AB  - OBJECTIVES: The purpose of this study was to examine the renal effects of a V2
      receptor arginine vasopressin (AVP) antagonist in heart failure. BACKGROUND:
      Arginine vasopressin has been implicated in the renal water retention and
      dilutional hyponatremia associated with chronic heart failure. METHODS: We
      examined the effects of the oral, non-peptide, selective V2 receptor antagonist
      lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure
      in a randomized, double-blind, placebo-controlled, ascending single-dose study.
      After overnight fluid deprivation, patients received single-blind placebo on day 
      1 (baseline) and double-blind study medication (placebo [n = 12] or lixivaptan
      10, 30, 75, 150, 250, or 400 mg [n = 5 per dose group]) on day 1, followed by 4 h
      of continued fluid restriction and additional 20 h with ad libitum fluid intake.
      RESULTS: At all but the 10-mg dose, lixivaptan produced a significant and dose
      related increase in urine volume over 4 h, compared with placebo. During 24 h,
      increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400
      mg lixivaptan dose (p < 0.01). These increases in urine volumes were accompanied
      by significant increases in solute-free water excretion. At higher doses, serum
      sodium was significantly increased; AVP antagonism was well tolerated in these
      patients. CONCLUSIONS: These observations confirm a role for AVP in the renal
      water retention associated with heart failure and suggest that the V2 receptor
      antagonist lixivaptan may be a promising therapeutic agent for the treatment of
      heart failure.

PMID- 16631000
TI  - Coronary endothelial vasomotor function and vascular remodeling in heart
      transplant recipients randomized for tacrolimus or cyclosporine
      immunosuppression.
AB  - OBJECTIVES: This study aimed to compare changes in coronary endothelial function,
      systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant
      recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac)
      immunosuppression. BACKGROUND: Functional endothelial abnormalities and intimal
      thickening are sensitive measures of early cardiac allograft vasculopathy (CAV).
      METHODS: The randomized, prospective study was performed in two groups of 22
      patients, maintained on Tac or CyA and mycophenolate mofetil immunosuppression, 1
      and 12 months after heart transplantation. We investigated epicardial luminal
      diameter, coronary blood flow velocity, and ET-1 plasma levels at 1 and 12 months
      after transplantation. Structural coronary alterations were determined using
      intravascular ultrasound. RESULTS: Epicardial vasomotor function at baseline and
      during follow-up was comparable between the groups. Deterioration of
      microvascular endothelial function during follow-up was significantly enhanced in
      the CyA versus Tac group (p < 0.05). Circulating ET-1 concentration increased in
      the CyA group but significantly decreased over time in the Tac group (CyA +17%
      vs. Tac -25%; p < 0.05). The time-dependent increase in mean intimal area was
      significantly enhanced in the CyA versus Tac group, whereas the vessel area
      significantly increased during follow-up in the Tac compared with the CyA group.
      CONCLUSIONS: Epicardial endothelial function is comparable between CyA- and Tac
      treated patients. Microvascular endothelial function deteriorates more in CyA
      treated patients, a finding that correlates with enhanced ET-1 concentration and
      an increased intimal area during follow-up. The mean vessel area in the Tac group
      increased over time, indicating positive vascular remodeling. Tac is superior to
      CyA with respect to microvascular endothelial function, intimal thickening, and
      vascular remodeling.

PMID- 16631001
TI  - Improved detection of coronary artery disease by stress perfusion cardiovascular
      magnetic resonance with the use of delayed enhancement infarction imaging.
AB  - OBJECTIVES: We tested a pre-defined visual interpretation algorithm that combines
      cardiovascular magnetic resonance (CMR) data from perfusion and infarction
      imaging for the diagnosis of coronary artery disease (CAD). BACKGROUND:
      Cardiovascular magnetic resonance can assess both myocardial perfusion and
      infarction with independent techniques in a single session. METHODS: We
      prospectively enrolled 100 consecutive patients with suspected CAD scheduled for
      X-ray coronary angiography. Patients had comprehensive clinical evaluation,
      including Rose angina questionnaire, 12-lead electrocardiography, C-reactive
      protein, and calculation of Framingham risk. Cardiovascular magnetic resonance
      included cine, adenosine-stress and rest perfusion-CMR, and delayed enhancement
      CMR (DE-CMR) for infarction imaging. Matched stress-rest perfusion defects in the
      absence of infarction by DE-CMR were considered artifactual. All patients
      underwent X-ray angiography within 24 h of CMR. RESULTS: Ninety-two patients had
      complete CMR examinations. Significant CAD (> or =70% stenosis) was found in 37
      patients (40%). The combination of perfusion and DE-CMR had a sensitivity,
      specificity, and accuracy of 89%, 87%, and 88%, respectively, for CAD diagnosis,
      compared with 84%, 58%, and 68%, respectively, for perfusion-CMR alone. The
      combination had higher specificity and accuracy (p < 0.0001), owing to
      incorporating the exceptionally high specificity (98%) of DE-CMR. Receiver
      operating characteristic curve analysis demonstrated the combination provided
      better performance than cine, perfusion, or DE-CMR alone. The accuracy was high
      in single-vessel and multivessel disease and independent of CAD location.
      Multivariable analysis including standard clinical parameters demonstrated the
      combination was the strongest independent CAD predictor. CONCLUSIONS: A combined
      perfusion and infarction CMR examination with a visual interpretation algorithm
      can accurately diagnose CAD in the clinical setting. The combination is superior
      to perfusion-CMR alone.

PMID- 16631002
TI  - When two tests are better than one: adding late gadolinium enhancement to first
      pass perfusion cardiovascular magnetic resonance.

PMID- 16631003
TI  - Reproducibility of chronic and acute infarct size measurement by delayed
      enhancement-magnetic resonance imaging.
AB  - OBJECTIVES: The aim of this study was to evaluate the reproducibility of acute
      and chronic infarct size (IS) by delayed enhancement (DE) magnetic resonance
      imaging (MRI). BACKGROUND: Infarct size measurements can be used as surrogate end
      point to reduce the sample size in studies comparing different reperfusion
      strategies in myocardial infarction (MI). Delayed enhancement MRI is a rather new
      technique, and so far infarct IS reproducibility has not been established
      appropriately. METHODS: In 21 patients (10 acute MI and 11 chronic MI), IS was
      assessed repeatedly on consecutive days by DE-MRI. Reproducibility,
      interobserver, and intraobserver variabilities were assessed and compared by the
      Bland-Altman method. RESULTS: Acute and chronic IS were 17.1 +/- 19.6% (range
      5.1% to 69.8%) of LV mass (%LV) and 16.9 +/- 9.9 %LV (range 2.0% to 36.0%),
      respectively. Infarct size difference (bias) between scan I and scan II was -0.5
      %LV, and limits of agreement were +/-2.4 %LV. Mean bias (-0.7 %LV) and limits of
      agreement (+/-3.2%) were slightly higher for acute in comparison with chronic MI
      with -0.4 +/- 1.3 %LV. Intraobserver and interobserver variability was low with a
      mean bias of 0.3 %LV (limits of agreement +/- 1.7 %LV) and -0.7 %LV (limits of
      agreement +/- 2.2 %LV), respectively. CONCLUSIONS: Infarct size measurement by DE
      MRI is an excellent tool for IS assessment, owing to its excellent repeatability
      in chronic and acute MI. It has therefore the potential to serve as a surrogate
      end point to uncover advantages of new reperfusion strategies.

PMID- 16631004
TI  - Positively magnetic north.

PMID- 16631005
TI  - Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic
      myocarditis presenting with heart failure or recurrent arrhythmias.
AB  - OBJECTIVES: We evaluated the effectiveness of contrast-enhanced cardiac magnetic
      resonance (CE-CMR) in detecting chronic myocarditis (CM). BACKGROUND: Chronic
      myocarditis represents a common evolution of acute myocarditis. Although CE-CMR
      has been revealed to be effective in identifying areas of myocardial damage in
      acute myocarditis, its role in the diagnosis of chronic myocardial inflammation
      has not yet been investigated. METHODS: Twenty-three patients with CM underwent
      CE-CMR and endomyocardial biopsy (EMB). Chronic myocarditis was defined by the
      presence of: 1) chronic (>6 months) heart failure symptoms and/or repetitive
      ventricular arrhythmias; 2) no history of recent flu-like symptoms or infections;
      and 3) histologic evidence of active myocarditis (AM) or borderline myocarditis
      (BM) according to Dallas criteria. Contrast-enhanced cardiac magnetic resonance
      included black-blood T2-weighted (BBT2w) images without and with fat saturation
      and delayed three-dimensional T1 turbo field-echo inversion-recovery sequences
      obtained 15 min after gadolinium injection. RESULTS: Histology showed AM in 14
      patients and BM in 9 patients. FatSat BBT2w revealed the presence of edema in
      five (36%) patients with AM but not in BM patients. Areas of late enhancement
      (LE) were observed in 12 (84%) subjects with AM and in 4 (44%) cases with BM. A
      mid-wall LE pattern was the most frequent finding in both groups while a
      subepicardial distribution of LE was observed only in patients with AM.
      CONCLUSIONS: Contrast-enhanced cardiac magnetic resonance identified areas of
      myocardial inflammation in up to 70% of patients with biopsy-proven CM. We
      suggest that CE-CMR may be a useful non-invasive diagnostic tool in patients with
      CM, and it may indicate and even guide the execution of left ventricular EMB with
      relevant prognostic and therapeutic implications.

PMID- 16631006
TI  - Noninvasive assessment of plaque morphology and composition in culprit and stable
      lesions in acute coronary syndrome and stable lesions in stable angina by
      multidetector computed tomography.
AB  - OBJECTIVES: The purpose of this study was to assess morphology and composition of
      culprit and stable coronary lesions by multidetector computed tomography (MDCT).
      BACKGROUND: Noninvasive identification of culprit lesions has the potential to
      improve noninvasive risk stratification in patients with acute chest pain.
      METHODS: Thirty-seven patients with acute coronary syndrome (ACS) or stable
      angina underwent coronary 16-slice MDCT and invasive selective angiography. In
      all significant coronary lesions two observers measured the degree of stenosis,
      plaque area at stenosis, and remodeling index and assessed plaque composition.
      Differences between culprit lesions in patients with ACS and stable lesions in
      patients with ACS or stable angina were determined. RESULTS: We analyzed 40
      lesions with excellent image quality in 14 patients with ACS and 9 patients with
      stable angina. Culprit lesions in patients with ACS (n = 14) had significantly
      greater plaque area and a higher remodeling index than both stable lesions in
      patients with ACS (n = 13) and in patients with stable angina (n = 13) (17.5 +/-
      5.9 mm2 vs. 9.1 +/- 4.8 mm2 vs. 13.5 +/- 10.7 mm2, p = 0.02; and 1.4 +/- 0.3 vs.
      1.0 +/- 0.4 vs. 1.2 +/- 0.3, p = 0.04, respectively). The prevalence of non
      calcified plaque was 100%, 62%, and 77%, respectively, and the prevalence of
      calcified plaque was 71%, 92%, and 85%, respectively, in culprit lesions in
      patients with ACS and in stable lesions in patients with ACS or stable angina.
      CONCLUSIONS: We introduce the concept of noninvasive detection and
      characterization of coronary atherosclerotic lesions in patients with ACS by
      MDCT. We identified differences in lesion morphology and plaque composition
      between culprit lesions in ACS and stable lesions in ACS or stable angina,
      consistent with previous intravascular ultrasound studies.

PMID- 16631007
TI  - Fabry's disease cardiomyopathy: echocardiographic detection of endomyocardial
      glycosphingolipid compartmentalization.
AB  - OBJECTIVES: We sought to identify echocardiographic hallmarks of Fabry's disease
      cardiomyopathy (FC). BACKGROUND: The recognition of FC from other forms of left
      ventricular hypertrophy (LVH) by noninvasive imaging techniques is not yet
      available, and diagnosis, mostly in the absence of systemic manifestations, still
      relies on genetic and invasive studies. METHODS: Forty consecutive patients (mean
      age 39 +/- 15 years, 22 men and 18 women) with an established diagnosis of
      Fabry's disease were submitted to echocardiographic evaluation. Control
      population consisted of 40 consecutive patients with hypertrophic cardiomyopathy
      (HCM), 40 hypertensive patients with echocardiographic evidence of LVH, and 40
      age- and gender-matched healthy subjects with no LVH. All HCM patients and FC
      with LVH and/or cardiac symptoms underwent cardiac catheterization with left
      ventricular endomyocardial biopsy. RESULTS: Echocardiography showed in 83% of FC
      patients (95% of FC patients with LVH) a binary appearance of endocardial border
      absent in all HCM, hypertensive, and healthy subjects. The sensitivity and
      specificity of this echocardiographic feature in detecting Fabry patients in
      study population were 94% and 100%, respectively. Comparison of echocardiographic
      with histologic and ultrastructural findings showed the binary appearance to
      reflect an endomyocardial glycosphingolipids compartmentalization, consisting of
      thickened glycolipid-rich endocardium, free glycosphingolipid subendocardial
      storage, and an inner severely affected myocardial layer with a clear
      subendocardial-midwall layer gradient of disease severity. CONCLUSIONS:
      Echocardiographic binary appearance of left ventricular endocardial border,
      reflecting endomyocardial glycosphingolipids compartmentalization, represents a
      sensitive and specific diagnostic hallmark of Fabry's disease cardiomyopathy.

PMID- 16631008
TI  - Grading of myocardial dysfunction by tissue Doppler echocardiography: a
      comparison between velocity, displacement, and strain imaging in acute ischemia.
AB  - OBJECTIVES: The aim of the study was to compare the ability of the tissue Doppler
      echocardiographic imaging (TDI) modalities velocity, strain, and displacement to
      quantify systolic myocardial function. BACKGROUND: Several TDI modalities may be
      used to quantify regional myocardial function, but it is not clear how the
      different modalities should be applied. METHODS: In 10 anesthetized dogs we
      measured left ventricular pressure, longitudinal myocardial velocity, strain, and
      displacement by TDI at baseline and during left anterior descending coronary
      artery (LAD) stenosis and occlusion. Reference methods were segmental shortening
      by sonomicrometry and segmental work. In 10 patients with acute anterior wall
      infarction (LAD occlusion) and 15 control subjects, velocity, strain, and
      displacement measurements were performed. RESULTS: In the animal study, systolic
      strain correlated well with segmental shortening (r = 0.96, p < 0.01) and work (r
      = 0.90, p < 0.01), and differentiated well between non-ischemic (-13.5 +/- 3.2%
      [mean +/- SD]), moderately ischemic (-6.5 +/- 2.8%), and severely ischemic
      myocardium (7.1 +/- 13.2%). The ratio post-systolic strain/total strain also
      differentiated well between levels of ischemia. Displacement and ejection
      velocity had weaker correlations with segmental shortening (r = 0.92 and r =
      0.74, respectively) and regional work (r = 0.85 and r = 0.69), and there was
      marked overlap between values at baseline and at different levels of ischemia. In
      the human study, systolic strain differentiated well between infarcted and normal
      myocardium (1.0 +/- 5.0% vs. -17.8 +/- 3.8%), whereas systolic displacement (-0.3
      +/- 1.3 mm vs. -2.3 +/- 0.6 mm) and ejection velocity (0.9 +/- 0.6 cm/s vs. 2.2
      +/- 0.6 cm/s) showed overlap. In the infarction group, strain was reduced in
      segments with infarcted tissue, while systolic velocity and displacement were
      reduced in all segments and did not reflect the extension of the infarct.
      CONCLUSIONS: Strain was superior to velocity and displacement for quantification
      of regional myocardial function. Provided technical limitations can be solved,
      strain Doppler is the preferred TDI modality for assessing function in ischemic
      myocardium.

PMID- 16631009
TI  - The relationship between stature and the prevalence of atrial fibrillation in
      patients with left ventricular dysfunction.
AB  - OBJECTIVES: This study sought to determine the influence of stature on atrial
      fibrillation (AF) in high-risk patients with reduced left ventricular (LV)
      systolic function. BACKGROUND: Left atrial (LA) enlargement is a potent risk
      factor for AF. Because LA size is strongly associated with stature, we
      hypothesized that height and body surface area (BSA) are risk factors for AF,
      independent of other known associations. METHODS: Data were obtained from
      ADVANCENT, a multicenter registry of patients with impaired LV function. Height
      and BSA were divided into quartiles by gender. Statistical analysis was done
      using the Cochran Mantel-Haenszel statistic, and multivariable logistic
      regressions were used to adjust for the effects of known confounders on the
      association between stature and AF. RESULTS: A total of 25,268 patients were
      enrolled. The mean age was 66 years, and the cohort consisted mostly of white men
      (72%) and patients with ischemic cardiomyopathy (72%). The mean left ventricular
      ejection fraction was 31%. A history of AF was present in 7,027 patients (27.8%).
      The AF prevalence increased significantly between the lowest and highest
      quartiles for height (32% relative increase, p < 0.0001). In the multivariable
      analysis, the effect of height on AF risk persisted after adjusting for age,
      gender, race, left ventricular ejection fraction, heart failure class and
      etiology, hypertension, diabetes, and medication use (odds ratio 1.026/cm, 95%
      confidence interval [CI] 1.022 to 1.030). In the multivariable analysis, BSA was
      also an independent predictor of AF risk (odds ratio 4.221/m2, 95% CI 3.358 to
      5.306). CONCLUSIONS: In patients with LV dysfunction, increasing stature portends
      a higher risk of AF independent of other traditional risk factors for the
      arrhythmia. This association seems to account for the higher prevalence of AF in
      men and may be useful for identification of a high-risk population.

PMID- 16631010
TI  - The year in interventional cardiology.

PMID- 16631011
TI  - Human degenerative valve disease is associated with up-regulation of low-density
      lipoprotein receptor-related protein 5 receptor-mediated bone formation.
AB  - OBJECTIVES: The goal of this research was to define the cellular mechanisms
      involved in myxomatous mitral valve disease and calcific aortic valve disease and
      to redefine the term degenerative valve disease in terms of an active cellular
      biology. BACKGROUND: "Degenerative" valvular heart disease is the primary cause
      of regurgitant and stenotic valvular lesion in the U.S. However, the signaling
      pathways are not known. We hypothesize that valve degeneration occurs due to an
      osteoblastic differentiation process mediated by the low-density lipoprotein
      receptor-related protein 5 (Lrp5) signaling pathway to cause valve thickening.
      METHODS: We examined human diseased valves: myxomatous mitral valves (n = 23),
      calcified tricuspid aortic valves (n = 27), calcified bicuspid aortic valves (n =
      23), and control tissue from mitral and aortic valves (n = 40). The valves were
      examined by reverse transcriptase-polymerase chain reaction, Western blot, and
      immunohistochemistry for signaling markers important in osteoblast
      differentiation: Sox9 and Cbfa1 (transcription factors for osteoblast
      differentiation); Lrp5 and Wnt3 (osteoblast differentiation signaling marker),
      osteopontin and osteocalcin (osteoblast endochrondral bone matrix proteins), and
      proliferating cell nuclear antigen (a marker of cell proliferation). Cartilage
      development and bone formation was measured by Alcian blue stain and Alizarin red
      stain. Computed Scano MicroCT-40 (Bassersdorf, Switzerland) analysis measured
      calcium burden. RESULTS: Low-density lipoprotein receptor-related protein 5,
      osteocalcin, and other osteochrondrogenic differentiation markers were increased
      in the calcified aortic valves by protein and gene expression (p > 0.001). Sox9,
      Lrp5 receptor, and osteocalcin were increased in myxomatous mitral valves by
      protein and gene expression (p > 0.001). MicroCT was positive in the calcified
      aortic valves and negative in the myxomatous mitral valves. CONCLUSIONS: The
      mechanism of valvular heart disease involves an endochondral bone process that is
      expressed as cartilage in the mitral valves and bone in the aortic valves. Up
      regulation of the Lrp5 pathway may play a role in the mechanism for valvular
      heart disease.

PMID- 16631012
TI  - A total of 1,007 percutaneous coronary interventions without onsite cardiac
      surgery: acute and long-term outcomes.
AB  - OBJECTIVES: We sought to compare clinical outcomes of elective percutaneous
      coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial
      infarction (STEMI) at a community hospital without onsite cardiac surgery to
      those at a tertiary center with onsite cardiac surgery. BACKGROUND: Disagreement
      exists about whether hospitals with cardiac catheterization laboratories, but
      without onsite cardiac surgery, should develop PCI programs. Primary PCI for
      STEMI at hospitals without onsite cardiac surgery have achieved satisfactory
      outcomes; however, elective PCI outcomes are not well defined. METHODS: A total
      of 1,007 elective PCI and primary PCI procedures performed from March 1999 to
      August 2005 at the Immanuel St. Joseph's Hospital-Mayo Health System (ISJ) in
      Mankato, Minnesota, were matched one-to-one with those performed at St. Mary's
      Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case
      selection and PCI program requirements. Clinical outcomes (in-hospital procedural
      success, death, any myocardial infarction, Q-wave myocardial infarction, and
      emergency coronary artery bypass surgery) and follow-up survival were compared
      between groups. RESULTS: Among 722 elective PCIs, procedural success was 97% at
      ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI,
      procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ
      undergoing PCI required emergent transfer for cardiac surgery. Survival at two
      years' follow-up by treatment location was similar for patients with elective PCI
      and primary PCI. CONCLUSIONS: Similar clinical outcomes for elective PCI and
      primary PCI were achieved at a community hospital without onsite cardiac surgery
      compared with those at a tertiary center with onsite cardiac surgery using a
      prospective, rigorous protocol for case selection and PCI program requirements.

PMID- 16631013
TI  - The unsung hero.

PMID- 16631014
TI  - Transthyretin V122I in African Americans with congestive heart failure.

PMID- 16631015
TI  - Influence of proteinuria on cardiovascular risk and response to angiotensin
      converting enzyme inhibition after myocardial infarction.

PMID- 16631016
TI  - Intracoronary delivery of hematopoietic bone marrow stem cells and luminal loss
      of the infarct-related artery in patients with recent myocardial infarction.

PMID- 16631017
TI  - Glucose-insulin-potassium infusion in patients with acute myocardial infarction
      without signs of heart failure: the Glucose-Insulin-Potassium Study (GIPS)-II.

PMID- 16631018
TI  - Impaired stroke volume response to exercise in pulmonary arterial hypertension.

PMID- 16631019
TI  - Release of C-reactive protein by stenting.

PMID- 16631020
TI  - Coronary arteries after arterial switch surgery.

PMID- 16631024
TI  - Microvolt T-wave alternans: where do we go from here?

PMID- 16631026
TI  - The big chill: adverse effects of public reporting on access to health care.

PMID- 16631027
TI  - New options for IOL calculations after refractive surgery.

PMID- 16631028
TI  - Another view of neodymium:YAG capsulotomy.

PMID- 16631030
TI  - Monocular versus binocular pupillometry.

PMID- 16631031
TI  - Safety of intracameral mydriasis in phacoemulsification cataract surgery.

PMID- 16631032
TI  - Need for strict aseptic separation of the 2 procedures in simultaneous bilateral
      cataract surgery.

PMID- 16631033
TI  - The cornea is stable during accommodation.

PMID- 16631034
TI  - Eyelid contamination as a cause of endophthalmitis.

PMID- 16631035
TI  - Consultation section: Refractive surgical problem.

PMID- 16631043
TI  - Crisscross lensotomy: New explantation technique.
AB  - Crisscross lensotomy is a new technique for removing a silicone plate intraocular
      lens (IOL) through a small incision. A case is described in which strategic
      incisions in the IOL allowed the lens to be explanted in pieces through a 3.0 mm
      incision. Less invasive surgery may enhance safety in complicated cases.

PMID- 16631044
TI  - Trypan blue to aid visualization of the vitreous during anterior segment surgery.
AB  - We describe the usefulness of intracameral injection of trypan blue to highlight
      vitreous in the anterior chamber. The technique was used in 3 eyes of 3 patients
      who had vitreous prolapse in the anterior chamber. Trypan blue 0.06% was injected
      in the anterior chamber under air to visualize and resect the prolapsed vitreous.
      Trypan blue stained the clear vitreous and improved visualization for a safe and
      atraumatic vitrectomy. No complications associated with the dye were found.

PMID- 16631045
TI  - Capsular stabilization device to preserve lens capsule integrity during
      phacoemulsification with a weak zonule.
AB  - We describe a new capsular stabilization device for suspending a lens with weak
      zonular support. It is flexible, 10.0 mm in length, and fashioned from 5-0 nylon.
      The contact portion is bent at 1.25 mm with an end bifurcating to form a T-shape
      to minimize stress on the capsular equator. After a continuous curvilinear
      capsulorhexis is created, the capsular stabilization devices to hook the
      capsulotomy margin are inserted. The T-shaped end is passed around the anterior
      capsular flap to fit the curvature of the equator. Phacoemulsification and
      aspiration using this device was performed in 12 eyes of 9 patients, and the
      usefulness and complications were analyzed. The capsular stabilization devices
      suspended the capsule and facilitated safe phacoemulsification in all eyes.
      Posterior capsule rupture occurred in 2 eyes. None of the cases had notable
      postoperative complications. This device ensures a stable capsule-iris complex
      and reduces surgical risks.

PMID- 16631046
TI  - ESCRS study of prophylaxis of postoperative endophthalmitis after cataract
      surgery: Case for a European multicenter study.
AB  - PURPOSE: To present the development and design of the European Society of
      Cataract & Refractive Surgeons multicenter study of the prevention of
      postsurgical infective endophthalmitis after phacoemulsification and to describe
      the process for its successful implementation and conduct. SETTING: Twenty-four
      ophthalmology units and eye clinics in Austria, Belgium, Germany, Italy, Poland,
      Portugal, Spain, Turkey, and the United Kingdom, with an administrative office in
      Ireland, coordinating center in England, and data management and statistical unit
      in Scotland. METHODS: This partially masked randomized placebo-controlled
      multinational clinical study was designed to evaluate prospectively the
      prophylactic effect of intracameral cefuroxime and/or perioperative topical
      levofloxacin on postoperative endophthalmitis after cataract surgery. Random
      allocation was based on a 2 x 2 factorial design that included participating
      centers as a class variable. Real-time electronic data collection monitored study
      progress and provided weekly outcome tables, monthly recruitment summaries, and
      quarterly analytical reports for the study's Data Monitoring Committee, which
      evaluated the safety and efficacy by Internet-based conferences. RESULTS: A 2
      year lead time was required to meet harmonized standards of clinical research in
      the European Union, obtain ministerial authorization in 3 countries, gain
      institutional approvals at 24 hospitals, and procure indemnity insurance for
      surgical centers. Informed consent instruments, designed to comply with national
      health policies, were translated into 8 languages. The use of information
      technology to collect study data enabled the organizers to evaluate individual
      eligibility at enrollment, adherence with study medications during and after
      surgery, and postoperative status during follow-up. CONCLUSION: This
      international cooperative study provided the opportunity to estimate the current
      incidence of endophthalmitis after cataract surgery in Europe and determine
      whether 1 or both of 2 antimicrobial regimens reduces the risk for postsurgical
      intraocular infection.

PMID- 16631047
TI  - ESCRS study of prophylaxis of postoperative endophthalmitis after cataract
      surgery: Preliminary report of principal results from a European multicenter
      study.
AB  - PURPOSE: To report results in the European Society of Cataract & Refractive
      Surgeons (ESCRS) multicenter study of the prophylaxis of endophthalmitis after
      cataract surgery. SETTING: Twenty-four ophthalmology units and eye clinics in
      Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United
      Kingdom, with an administrative office in Ireland, coordinating center in
      England, and data management and statistical unit in Scotland. METHODS: This
      partially masked randomized placebo-controlled multinational clinical study to
      evaluate prospectively the prophylactic effect of intracameral cefuroxime
      injection and/or perioperative levofloxacin eyedrops on the incidence of
      endophthalmitis after phacoemulsification cataract surgery began in September
      2003 and was terminated early in January 2006. The study used random allocation
      of patients in a 2 x 2 factorial design. RESULTS: By the end of 2005, complete
      follow-up records had been received for 13 698 study patients. Such a clear
      beneficial effect from the use of intracameral cefuroxime had been observed that
      it was agreed it would be unethical to continue the study and to wait for the
      completion of all follow-up procedures before reporting this important result. If
      total reported cases of endophthalmitis are considered, the incidence rate
      observed in those treatment groups not receiving cefuroxime prophylaxis (23 cases
      in 6862 patients) was almost 5 times as high (odds ratio [OR], 4.59; 95%
      confidence interval [CI], 1.74-12.08; P = .002) as that in the groups receiving
      this treatment (5 cases in 6836 patients). If only cases proved to be due to
      infection are considered, the rate was more than 5 times as high (OR, 5.32; 95%
      CI, 1.55-18.26; P = .008) in the treatment groups not receiving cefuroxime.
      Although the use of perioperative levofloxacin eyedrops as prophylaxis was also
      associated with a reduction in the observed incidence rate of postoperative
      endophthalmitis, this effect was smaller and was not statistically significant,
      whether total reported cases or only cases proven to be due to infection are used
      in calculating the rates. As not all follow-up procedures are complete, it is
      possible that further cases of endophthalmitis may be reported; however, it is
      not expected that this will alter the main conclusion. Nevertheless, it is
      anticipated that successful completion of follow-up procedures in all patients
      will increase the total number in the study to approximately 16,000. CONCLUSION:
      Intracameral cefuroxime administered at the time of surgery significantly reduced
      the risk for developing endophthalmitis after cataract surgery.

PMID- 16631048
TI  - Descemet's stripping with endothelial keratoplasty in 200 eyes: Early challenges
      and techniques to enhance donor adherence.
AB  - PURPOSE: To describe early challenges and techniques to promote donor tissue
      adherence in Descemet's stripping with endothelial keratoplasty (DSEK). SETTING:
      Price Vision Group, Indianapolis, Indiana, USA. METHODS: The first 200
      consecutive cases of DSEK performed by a single surgeon were analyzed
      retrospectively. Follow-up was 7 to 20 months for 124 eyes and 2 to 6 months for
      76 eyes. The surgical technique consisted of stripping Descemet's membrane and
      endothelium from the recipient's central cornea and transplanting an 8.0 to 9.0
      mm disc of donor endothelium and posterior stroma through a 5.0 mm incision, with
      sutures used only to close the incision. RESULTS: The most frequent challenge was
      inadequate donor attachment. Using techniques to remove fluid from the donor
      recipient graft interface, the donor detachment rate in the last 64 cases was 6%,
      with half attributable to patient eye rubbing. Detached grafts were reattached by
      injecting an air bubble to press the donor against the recipient cornea. There
      were 7 primary graft failures, with only 1 occurring in the second 100 cases,
      which primarily used microkeratome-dissected donor tissue. Other complications
      were infrequent and included pupillary block glaucoma (1), aqueous misdirection
      syndrome (1), and cataract development in 2 of 27 phakic eyes. The DSEK procedure
      was performed safely before and after laser in situ keratomileusis (1 each).
      CONCLUSIONS: Early outcomes in the initial 200 consecutive DSEK procedures
      suggest the technique provides significant advantages over penetrating
      keratoplasty, including more rapid healing, more predictable refractive outcomes,
      and better retention of corneal strength and integrity. Although donor adherence
      was more challenging, DSEK was technically easier and should be less traumatic to
      anterior chamber structures than earlier posterior grafting techniques.

PMID- 16631049
TI  - Prediction of the effective postoperative (intraocular lens) anterior chamber
      depth.
AB  - PURPOSE: To investigate methods to predict the effective postoperative anterior
      chamber depth (ACD) based on a large patient sample. SETTING: University Eye
      Clinic, Aarhus Kommunehospital, Aarhus, Denmark. METHODS: Based on 6698
      consecutive cataract operations with recorded postoperative refractive results,
      the postoperative effective ACD was calculated in each case and studied by
      multiple linear regression for covariance with a number of preoperatively defined
      variables including the axial length by ultrasonography, preoperative ACD, lens
      thickness, corneal radius by keratometry, subjective refraction, patient age, and
      corneal white-to-white diameter, the latter of which was available in a subgroup
      of 900 cases. RESULTS: The postoperative effective ACD was significantly
      correlated with 6 preoperative variables (in decreasing order): axial length,
      preoperative ACD, keratometry reading, lens thickness, refraction, and patient
      age (R = 0.49, P < .000001). Age showed the weakest correlation (P = .02) and
      could be omitted with no significant decrease in the total correlation
      coefficient. Using the 5 most significant variables, the ACD could be predicted
      according to a regression formula with an accuracy of 82.1% of the predictions
      within 0.5 mm. When this ACD algorithm was used in retrospect in the intraocular
      lens (IOL) power calculation, the refractive prediction error decreased by 10%
      from the error associated with a previously published 4-variable algorithm and
      decreased 28% from the error using no individual ACD method other than the
      average ACD (P < .00001). CONCLUSIONS: The postoperative ACD was significantly
      correlated with and hence predictable by a 5-variable regression method
      incorporating the preoperative axial length, ACD, keratometry reading, lens
      thickness, and refraction as the most significant variables. The statistical
      relationship can be used to create a new ACD prediction algorithm to incorporate
      in a modern "thick lens" IOL power calculation formula with significant
      improvement in the accuracy of the refractive predictions as a result.

PMID- 16631050
TI  - Accurate intraocular lens power calculation after myopic laser in situ
      keratomileusis, bypassing corneal power.
AB  - PURPOSE: To describe a novel method for calculating intraocular lens (IOL) power
      after myopic laser in situ keratomileusis (LASIK) without using the inaccuracies
      of the post-LASIK corneal power. SETTING: Department of Ophthalmology, Wake
      Forest University Eye Center, Wake Forest University School of Medicine, Winston
      Salem, North Carolina, USA. METHODS: This retrospective chart review comprised 9
      eyes of 9 patients who had phacoemulsification after LASIK using our method for
      IOL calculation. This new method assumes the patient never had myopic LASIK to
      calculate IOL power and then targets the IOL at the pre-LASIK amount of myopia.
      The pre-LASIK keratometry values, pre-LASIK manifest refraction, and the current
      axial length are placed in the Holladay formula, bypassing the post-LASIK corneal
      power. In theory, assuming that the patient had satisfactory LASIK results, the
      correct IOL can then be determined. RESULTS: The mean spherical equivalent
      postoperative refraction was +0.03 diopter (D) +/- 0.42 (SD) (range -0.625 to
      +0.75 D). In all 9 eyes, our method consistently chose the most accurate and
      precise IOL compared with other methods. CONCLUSIONS: The new method of
      calculating IOL power after LASIK provided excellent results and the most
      accurate and precise results to date.

PMID- 16631051
TI  - Simple regression formula for intraocular lens power adjustment in eyes requiring
      cataract surgery after excimer laser photoablation.
AB  - PURPOSE: To develop a simple and accurate method for determining appropriate
      intraocular lens (IOL) power in cataract patients who had prior excimer laser
      photoablation for myopia or hyperopia, because laser vision corrective surgery
      interferes with traditional keratometry and corneal topography, rendering IOL
      power calculations inaccurate. SETTING: Private Practice in Century City (Los
      Angeles), California, and free-standing outpatient surgery centers with
      institutional review boards. METHODS: Based on the empiric experience of the
      senior author, an IOL power correction factor that was proportional to the prior
      laser photoablation was determined and applied to the IOL power calculated by the
      IOLMaster (Zeiss). It was necessary to add to the predicted IOL power in eyes
      with prior myopic laser ablation, whereas eyes having prior hyperopic laser
      vision correction required a reduction in the IOL power. The correction factor
      was applied to 30 eyes that required cataract surgery at some time after laser
      refractive surgery; 23 eyes had prior treatment for myopia, and the remaining 7
      eyes had prior hyperopic laser ablation. A regression formula was generated from
      the IOL power correction factor that was used in the 30 eyes. RESULTS: Using the
      correction factor for 30 eyes, the mean deviation from the desired postcataract
      refractive outcome was -0.15 diopter (D) +/- 0.29 (SD); 28 of 30 eyes were within
      +/-0.5 D of the intended goal; the remaining 2 eyes were both -0.75 D from the
      desired optical result of cataract surgery. Fourteen of the 30 eyes were
      emmetropic. CONCLUSIONS: A simple IOL power corrective adjustment regression
      formula allowed accurate determination of IOL power after laser refractive
      photoablation surgery. The weakness of the current method is that knowledge of
      the amount of prior laser vision correction is necessary.

PMID- 16631052
TI  - Intraocular lens power calculation after laser in situ keratomileusis: Aphakic
      refraction technique.
AB  - PURPOSE: To evaluate the accuracy of a new method of intraocular lens (IOL) power
      calculation for eyes having cataract extraction after previous laser in situ
      keratomileusis (LASIK). SETTING: Clinical private practice and ambulatory
      surgical center, Astoria, New York, USA. METHODS: This retrospective study was of
      12 eyes of 9 patients who presented for cataract extraction after previous LASIK.
      Cataract removal was performed under topical anesthesia without IOL implantation.
      Approximately 30 minutes later, a manifest aphakic refraction was performed. The
      calculation of the IOL power was obtained by using an algorithm derived from
      previous experience with secondary IOL implantation (Mackool algorithm). The
      patient then returned to the operating room for lens implantation (aphakic
      refraction technique). RESULTS: The refractive error 2 weeks postoperatively,
      defined as the difference between the intended and actual refractive outcome,
      ranged from 0.50 diopter (D) of unintended hyperopia to 0.75 (D) of unintended
      myopia. CONCLUSIONS: The aphakic refraction technique provided an extremely
      accurate postoperative refraction in eyes having cataract with IOL implantation
      surgery after previous LASIK. Although the pool sample was small (12 eyes) and
      the range of the aphakic refraction was limited (+8.50 to 12.375 D), the
      technique was found to be remarkably accurate.

PMID- 16631053
TI  - Intracameral cefazolin as prophylaxis against endophthalmitis in cataract
      surgery.
AB  - PURPOSE: To evaluate the efficacy of prophylactic intracameral cefazolin in
      preventing endophthalmitis in cataract surgery. SETTING: Service of
      Ophthalmology, St. Joan Hospital, Reus, Spain. METHODS: In this noncontrolled
      retrospective observational study, all patients had uncombined cataract surgery
      from January 2001 to December 2004. All cases of postoperative endophthalmitis
      were related. The patients were classified into 2 groups. The first (n = 3650)
      had surgery between January 2001 and December 2002, and the second (n = 3618) had
      surgery between January 2003 and December 2004; the second group received a bolus
      of intracameral cefazolin instilled at the end of surgery. RESULTS: The rate of
      postoperative endophthalmitis was lower in the cases with intracameral injection
      at the end of surgery (0.055%) than in those without cefazolin injection (0.63%).
      No patients in the group with intracameral cefazoline developed corneal
      endothelium or retinal toxicity. CONCLUSIONS: Intracameral bolus injection of
      cefazolin (1 mg in 0.1 mL solution) in cataract surgery demonstrated prophylactic
      efficacy in diminishing the rate of postoperative endophthalmitis without toxic
      effects on the cornea or retina.

PMID- 16631054
TI  - Pseudophakic retinal detachment after phacoemulsification cataract surgery: Ten
      year retrospective review.
AB  - PURPOSE: To determine the risk for rhegmatogenous retinal detachment (RRD) after
      phacoemulsification. SETTING: Private and public facility, Auckland, New Zealand.
      METHODS: A retrospective study of 1793 consecutive patients having cataract
      surgery by phacoemulsification was performed. Patients younger than 40 years were
      excluded, as were patients who had cataract surgery after ocular trauma. Patients
      having cataract surgery combined with other ocular procedures such as
      keratoplasty, glaucoma drainage surgery, or posterior segment surgery were
      similarly excluded. RESULTS: Rhegmatogenous retinal detachment occurred in 1.17%
      of the patients having cataract surgery. The risk was greater in patients younger
      than 50 years (5.17%) and less in those older than 70 years (0.64%). The median
      interval between cataract surgery and development of the retinal detachment was
      39 months. The rate of retinal detachment was greater with complicated cataract
      surgery, but there was no increased risk for those eyes requiring neodymium:YAG
      laser capsulotomy. CONCLUSIONS: The overall risk for RRD after cataract surgery
      by phacoemulsification was small. However, in the younger patient, the risk for
      pseudophakic detachment was higher. In light of this finding, the requirement for
      cataract surgery in this group should be reassessed.

PMID- 16631055
TI  - Effect of laser in situ keratomileusis and laser-assisted subepithelial
      keratectomy on retinal nerve fiber layer thickness.
AB  - PURPOSE: To evaluate and compare the influence of laser in situ keratomileusis
      (LASIK) and laser-assisted subepithelial keratectomy (LASEK) on the peripapillary
      retinal nerve fiber layer (RNFL) thickness. SETTING: Observational case series.
      METHODS: Twenty nonglaucomatous patients with mild to moderate myopia were
      included. One eye in each patient was randomly selected to have LASIK (Group 1, n
      = 20), and LASEK was performed in the fellow eye (Group 2, n = 20). The RNFL
      thickness measurements were performed using optical coherence tomography (OCT)
      preoperatively and 1 day and 1 month postoperatively. The RNFL thickness
      parameters were compared using repeated-measures 1-way analysis of variance
      (ANOVA) followed by multiple comparison tests in both groups. The main outcome
      parameter was RNFL thickness as determined by OCT before and after LASIK and
      LASEK. RESULTS: The mean age of the patients was 21 years +/- 3.2 (SD). The mean
      preoperative spherical equivalent was -4.23 +/- 1.71 diopters (D) in Group 1 and 
      4.16 +/- 1.68 D in Group 2. The mean ablation depth was 73.35 +/- 27.85 microm
      and 66.35 +/- 23.64 microm in groups 1 and 2, respectively. In Group 1, the mean
      average RNFL thickness, inferior average, superior average, temporal average, and
      nasal average were 98.2 +/- 5.6 microm, 128.6 +/- 11.9 microm, 120.38 +/- 10.2
      microm, 65. 8+/- 7.1 microm, and 80.5 +/- 18.8 microm, respectively. None of the
      RNFL thickness parameters or RNFL ratios were found to have a significant change
      after surgery. In Group 2, the average RNFL thickness, inferior average, superior
      average, temporal average, and nasal average were 98.47 +/- 5.9 microm, 128.38 +/
      14.3 microm, 125.1 +/- 8.8 microm, 66.4 +/- 8.2 microm, 73.6 +/- 15.8 microm,
      respectively. No significant change was observed in any of the parameters
      following surgery. No significant alterations were noted in the RNFL parameters
      following LASIK or LASEK. CONCLUSIONS: Laser in situ keratomileusis and LASEK did
      not significantly affect the RNFL thickness parameters postoperatively.

PMID- 16631056
TI  - Visual performance: Comparison of foldable intraocular lenses.
AB  - PURPOSE: To compare best distance visual acuity, color perception, and contrast
      sensitivity between eyes with an AcrySof Natural intraocular lens (IOL) (Alcon
      Laboratories Inc.) and fellow eye with an AcrySof IOL and to compare results in
      the IOL groups to those in normal, similarly aged patients with clear phakic
      eyes. SETTING: Sri Sankaradeva Nethralaya, Guwahati, India. METHODS: This
      prospective randomized parallel group single-center patient-masked examiner
      masked study comprised 26 eyes of 13 healthy patients with bilateral age-related
      cataract. All patients had cataract surgery by phacoemulsification in both eyes;
      1 eye received an AcrySof Natural IOL (SN60AT) and the fellow eye, an AcrySof
      (SA60AT) IOL. Final postoperative examination was performed at the end of 18
      months. In addition to other findings, visual acuity, color perception, and
      contrast sensitivity were recorded. A group of normal, similarly aged phakic
      individuals with clear lenses was examined for contrast sensitivity. The records
      thus obtained were analyzed statistically. RESULTS: The AcrySof and AcrySof
      Natural IOL groups had a statistically significant improvement in visual acuity
      and color perception in comparison to preoperative status, and this was
      maintained until the last postoperative follow-up at 18 months. There was no
      statistically significant difference in the findings between the 2 IOL groups.
      The AcrySof and the AcrySof Natural IOL groups showed significant improvement in
      contrast sensitivity from the preoperative to the postoperative period (both P <
      .001). However, the AcrySof Natural IOL group was better than the AcrySof IOL
      group when each group was compared separately to similarly aged phakic
      individuals with clear lenses. CONCLUSIONS: Pseudophakia following AcrySof
      Natural SN60AT and AcrySof SA60AT IOL implantation led to equivalent visual
      acuity and color perception. But the contrast sensitivity in the AcrySof Natural
      group was better and near normal in reference to a healthy, age-matched control
      group.

PMID- 16631057
TI  - Anterior chamber measurements using Pentacam rotating Scheimpflug camera.
AB  - PURPOSE: To investigate the mean values and standard deviations according to age,
      reliability, and correlation between different parameters of anterior chamber
      measurements using the Pentacam rotating Scheimpflug camera. SETTING: Heidelberg
      IOL and Refractive Surgery Research Group, Department of Ophthalmology,
      University of Heidelberg, Heidelberg, Germany. METHODS: This prospective clinical
      study comprised 76 healthy volunteers (mean age 46.6 years +/- 16.8 [SD]). Three
      consecutive measurements were made of only 1 eye and anterior chamber depth
      (ACD), mean and minimum anterior chamber angle (ACA), and anterior chamber volume
      (ACV) were evaluated. RESULTS: Mean ACD was 2.93 +/- 0.36 mm, mean ACA was 34.81
      +/- 5.05 degrees, minimum ACA was 29.99 +/- 5.53 degrees, and mean ACV was 160.3
      +/- 36.81 mm3. Increasing age was associated with reduced ACD and ACV; however,
      mean and minimum ACAs were lowest in patients aged 40 to 59 years. Excellent
      correlation was found between ACD and ACV (R = 0.92). Anterior chamber depth and
      mean ACA correlated only moderately (R = 0.65). The correlation coefficient
      between ACD and minimum ACA was smaller (R = 0.58). There was no correlation
      between ACV and ACA (R = 0.37). Minor standard deviations were noted (ACD 0.02 +/
      0.02 mm, mean ACA 1.12 +/- 0.94 degrees, minimum ACA 2.04 +/- 2.67 degrees, and
      ACV 2.48 +/- 1.65 mm3). CONCLUSIONS: Using the Pentacam, it was possible to
      examine different parameters of the anterior chamber within a short period and
      with good reliability. The evaluation of the ACA in different positions can help
      to classify the potential risk for angle-closure glaucoma.

PMID- 16631058
TI  - Comparison of central corneal thickness measurements with a new optical device
      and a standard ultrasonic pachymeter.
AB  - PURPOSE: To compare central corneal thickness (CCT) values obtained with
      ultrasonic pachymetry and a new optical method using partial coherence
      interferometry (PCI). SETTING: Department of Ophthalmology, Medical Health and
      Science Center, University of Debrecen, Debrecen, Hungary. METHODS: The study
      comprised 136 eyes of 70 patients whose spherical refractive error was not
      greater than +/-6.0 diopters (D) and whose keratometric astigmatism was not
      greater than 2.0 D. Central corneal thickness was measured 5 times with a new
      optical device (ACMaster, Zeiss) and with an ultrasonic pachymeter (AL-2000,
      Tomey). All measurements were obtained by the same investigator. RESULTS: Mean
      CCT was 531.2 microm +/- 3.9 (SD) with PCI and 547.8 +/- 36.0 microm with the
      ultrasonic device. The difference between groups was significant (P = .001).
      There was no difference between CCT values measured in right and left eyes (P =
      .55) with ultrasonography and PCI (P = .67). The coefficient variation was 0.73%
      for PCI and 6.5% for ultrasonography. Correlation between the CCT measurements
      with both devices was strong and statistically significant (Spearman correlation
      = .91, P = .001). CONCLUSIONS: Mean CCT values measured by the PCI method were
      significantly smaller than those measured by the ultrasonic device. Central
      corneal thickness measured with PCI is more reproducible and seems to be more
      reliable than that measured by ultrasonography.

PMID- 16631059
TI  - Laser in situ keratomileusis in myopic patients with congenital nystagmus.
AB  - PURPOSE: To evaluate the results of laser in situ keratomileusis (LASIK) and
      IntraLASIK in the treatment of myopic patients with nystagmus. METHODS: Eight
      patients with congenital nystagmus (16 eyes), aged 23 to 49 years, had LASIK
      surgery. Corneal flaps were created using the Bausch & Lomb Hansatome
      microkeratome or the IntraLase femtosecond laser. The ablations were performed
      with the Bausch & Lomb excimer laser with an active tracking system. In some
      patients, the eyes were fixated with forceps or a fixation ring during laser
      ablation. RESULTS: The refractive errors were corrected in all cases. There was
      no decentration or loss of best corrected visual acuity greater than 1 line. In
      56% of the eyes, the postoperative uncorrected visual acuity was better than the
      best spectacle-corrected visual acuity (BSCVA). The BSCVA improved in 62.5% of
      the eyes. The overall visual performance improved in all patients. One patient
      who did not drive before surgery became eligible for a driver's license after
      surgery. CONCLUSIONS: Selected patients with myopia and congenital nystagmus may
      benefit from laser refractive surgery. Laser refractive surgery may be safely and
      accurately performed using the Hansatome microkeratome or the IntraLase
      femtosecond laser and an active tracking system with or without mechanical
      fixation. The BSCVA may improve in certain patients postoperatively.

PMID- 16631060
TI  - Single perioperative triamcinolone injection versus standard postoperative
      steroid drops after uneventful phacoemulsification surgery: Randomized controlled
      trial.
AB  - PURPOSE: To evaluate the safety and efficacy of a single perioperative sub
      Tenon's injection of triamcinolone following cataract surgery and its effect on
      the incidence of early pseudophakic cystoid macular edema (CME). SETTING:
      Ophthalmology Department, Queen's Medical Centre University Hospital, Nottingham.
      United Kingdom. METHODS: This prospective randomized controlled trial included 54
      eyes (54 patients) having routine cataract surgery. Twenty-seven eyes received
      the conventional postoperative care with steroid drops (drops group), whereas the
      other 27 were given a perioperative sub-Tenon's injection of triamcinolone
      (injection group); 10 of these received 20 mg, and the remaining 17 eyes had 30
      mg triamcinolone. All patients were evaluated preoperatively and at days 1, 8,
      30, and 90. The outcome measures evaluated were logMAR best corrected visual
      acuity (BCVA), anterior chamber flare (Kowa-500 flare meter), intraocular
      pressure, and slitlamp biomicroscopy. Oral fluorescein angiograms were performed
      at 30 and 90 days to detect angiographic CME. RESULTS: The mean logMAR BCVA
      improved from a baseline of 0.38 +/- 0.38 (SD) and 0.44 +/- 0.26 to 0.02 +/- 0.14
      and 0.0 +/- 0.07 at 90 days in the steroid drops and injection groups,
      respectively. (P = .59). The mean flare increased from a baseline of 8.9 +/- 3.2
      photons/ms and 8.3 +/- 3.7 photons/ms in the steroid drops and injection groups,
      respectively, to a maximum of +/-14.1 photons/ms and 25.8 +/- 7.5 photons/ms at
      day 8. Mean flare decreased to 15.8 +/- 9.7 photons/ms and 13.8 +/- 10.1
      photons/ms at 30 days (P = .48, difference between groups) and 10.4 +/- 3.6
      photons/ms and 9.8 +/- 3.1 photons/ms at 90 days, respectively, in the 2 groups.
      Subanalysis revealed lowest peak flare (17.9 +/- 7.9 photons/ms) at 8 days in the
      group that received 30 mg triamcinolone. CONCLUSIONS: A single sub-Tenon's
      injection of 30 mg triamcinolone seem to be safe and effective as a route of
      steroid delivery after uneventful phacoemulsification surgery. Larger numbers in
      patients at high risk are required to assess its effectiveness in reducing the
      risk for pseudophakic CME.

PMID- 16631061
TI  - CustomVue laser in situ keratomileusis for myopia and myopic astigmatism using
      the Visx S4 excimer laser: Efficacy, predictability, and safety.
AB  - PURPOSE: To evaluate the efficacy, predictability, and safety of custom laser in
      situ keratomileusis (LASIK) using the Visx wavefront platform CustomVue for the
      treatment of myopia and myopic astigmatism. SETTING: Stanford University Eye
      Laser Center, Stanford, California, USA. METHODS: This retrospective analysis was
      of the initial 140 eyes of 78 patients treated consecutively with LASIK for
      myopia using the Visx Star S4 excimer laser. Primary outcome variables, including
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      manifest refraction, and complications, were evaluated at 1 week and 1 and 3
      months. Vector analysis was performed on eyes that received astigmatic
      correction. RESULTS: Mean preoperative spherical equivalent (SE) was reduced from
      -3.89 diopters +/- 1.48 (SD) to an SE of -0.21 +/- 0.36 D at 1 month and -0.28 +/
      0.36 D at 3 months (P < .001). At 1 and 3 months, UCVA was 20/20 or better in
      84.3% and 87.9%, respectively. Eighty-six percent of eyes at 1 month and 81.4% of
      eyes at 3 months were within +/-0.5 D of emmetropia. No eyes lost more than 2
      lines of BSCVA. Vector analysis yielded an index of success of 0.39, indicating a
      61% success rate in achieving the astigmatic surgical correction at 3 months. The
      preoperative root-mean-square value of 0.28 +/- 0.08 microm increased slightly to
      0.33 +/- 0.11 microm at 1 month and 0.34 +/- 0.11 microm at 3 months. CONCLUSION:
      Wavefront-guided LASIK using the Visx CustomVue system was effective,
      predictable, and safe for correction of low to moderate myopic refractive error.

PMID- 16631062
TI  - Wound-healing response and refractive regression after conductive keratoplasty.
AB  - PURPOSE: To characterize the histological changes that occur after conductive
      keratoplasty (CK) using a rabbit model. SETTING: LSU Eye Center and Neuroscience
      Center of Excellence, Louisiana State University Health Sciences Center, School
      of Medicine, New Orleans, Louisiana, USA. METHODS: Conductive keratoplasty was
      performed on 24 eyes of 12 New Zealand albino rabbits. In each eye, 24 spots were
      placed in a cross-corneal manner using 3 optical zones at 6.0, 7.0, and 8.0 mm.
      Eyes were assessed with corneal topography weekly. Rabbits were humanely killed
      2, 4, 6, and 8 weeks postoperatively. The eyes were then enucleated and processed
      for histopathology and immunohistochemical analysis. RESULTS: All eyes showed an
      initial mean steepening of the corneal curvature of 2.24 diopters (D) 2 weeks
      postoperatively. Corneal topography revealed a 26%, 36%, and 39% regression of
      the refractive results at 4, 6, and 8 weeks, respectively. Immunohistochemical
      analysis demonstrated keratocyte apoptosis, myofibroblast appearance, and
      upregulation of chondroitin sulfate, MMP-1, and collagen III in the area
      surrounding the tip in each spot. CONCLUSION: The histological changes that occur
      after CK may be responsible for the well-established regression of its refractive
      effect. A better understanding of the wound-healing response after CK is
      necessary to improve the long-term stability of the procedure.

PMID- 16631063
TI  - Computer simulation of visual outcomes of wavefront-only corneal ablation.
AB  - PURPOSE: To evaluate the effectiveness, predicted visual outcome, and limitations
      of a corneal ablation algorithm that uses wavefront aberration measurement alone
      without the need for corneal shape information. SETTING: Contact Lens and Visual
      Optical Laboratory, School of Optometry, Queensland University of Technology,
      Brisbane, Australia. METHODS: Corneal topography and wavefront error data from 22
      eyes of 11 potential refractive surgery candidates were used. A computer
      simulation of the corneal ablation was performed, and the predicted postoperative
      visual outcome was assessed by calculating the resulting wavefront root-mean
      square (RMS) values and visual Strehl ratios. Additionally, the effect of
      ablation alignment error was examined. Finally, the visual outcomes of the
      wavefront-only corneal ablations were compared to those in an age-matched group
      of 20 emmetropic patients. RESULTS: Significant improvement in total and higher
      order wavefront RMS was achieved postoperatively in both an ideal setting and in
      the case of ablation alignment errors. The predicted improvement in visual Strehl
      ratio in the potential refractive surgery candidates was significantly better
      than that in the untreated emmetropes. After additional simulated decentration of
      the pupil center by 150 microm, the result was slightly worse, but the change was
      found to not be significant when compared to the retinal image quality of
      emmetropes. CONCLUSIONS: Wavefront-only corneal ablation algorithms could
      potentially lead to significantly better visual outcomes than those normally
      encountered in untreated emmetropes, provided that the alignment error is not
      large. The presented methodology may be used as a screening tool to predict
      patients' visual outcomes before the surgery.

PMID- 16631064
TI  - Irregularities on the surface of single-piece AcrySof SA60AT intraocular lenses.
AB  - PURPOSE: To report a case series of what initially appeared to be macroscopic
      biomaterial deposits and irregularities on the surface of AcrySof SA60AT
      intraocular lenses (IOLs) (Alcon Inc.) SETTING: Department of Ophthalmology and
      Somerset Hospital, Taunton, United Kingdom; Department of Ophthalmology and
      Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City,
      Utah, USA; and Intraocular Implant Unit, Sydney Eye Hospital, University of
      Sydney, Sydney, Australia. METHODS: Twelve AcrySof SA60AT IOLs were initially
      thought to have irregularities on their surfaces when examined under the
      operating microscope before implantation in the capsular bag during cataract
      surgery. The IOLs were sent for further analysis, including gross examination and
      light and scanning electron microscopy, to John A. Moran Eye Center, Salt Lake
      City, Utah, USA, and to Alcon Laboratories, Hemel Hempstead, United Kingdom.
      RESULTS: Light microscopy revealed the presence of irregular fine lesions on the
      IOLs' optics and haptics. The lesions consisted of elevations and depressions of
      the IOL surface that were present on both the anterior and the posterior surfaces
      of the IOLs. Scanning electron microscopy confirmed the presence of
      physical/mechanical damage to the IOLs, which was thought to originate from the
      packaging. The manufacturer believed this to have resulted from compression of
      the IOL between the container and its cover. CONCLUSIONS: Implantation of an
      imperfect IOL remains a potentially serious occurrence. Faults still occur in
      modern IOLs, and some defects can be detected by examining the IOL under the
      operating microscope before implantation into the eye.

PMID- 16631065
TI  - Early opacification of silicone intraocular lenses: Laboratory analyses of 6
      explants.
AB  - PURPOSE: To report laboratory analyses of 6 intraocular lenses (IOLs) explanted
      from patients who had visual disturbances caused by early postoperative
      opacification of the lens optic. SETTING: John A. Moran Eye Center, University of
      Utah, Salt Lake City, Utah, USA. METHODS: Six patients with 3-piece silicone
      lenses presented with optic cloudiness as early as a few hours after
      implantation. The lenses were implanted in 4 locations in Brazil and in France.
      The lenses in Brazil were stored at the same location before implantation. Gross
      and microscopic analyses were performed (dry and hydrated states). One half of
      each specimen underwent gas chromatography/mass spectrometry (GC/MS) analysis
      and/or extraction by isopropyl alcohol or acetonitrile. One lens also underwent
      scanning electron microscopy (SEM) with energy dispersive x-ray spectroscopy
      (EDS). The IOLs were examined for the presence of contaminants or deposits that
      could cause fast optic opacification. RESULTS: The IOLs showed a white optic
      discoloration in the hydrated state but became transparent on complete
      dehydration. Suspect exogenous chemical compounds were identified in GC/MS
      analyses; general classes included terpenes and ketones, typically found in
      industrial cleaning agents and fumigants. Surface analysis (SEM and EDS) did not
      show any significant deposits on the external surfaces and sagittal cut in 1 of
      the specimens. CONCLUSIONS: Most IOLs are enclosed in semipermeable packages to
      allow sterilization by ethylene oxide gas. During cleaning or disinfection of
      storage rooms, aerosolized solutions may introduce chemicals through the package
      and onto the IOLs. This may cause surface changes in the IOL, promoting
      opacification by water ingress in the aqueous environment. Cleaning and
      disinfection procedures of IOL storage areas should be monitored carefully.

PMID- 16631066
TI  - Effect of growth factors on proliferation and expression of growth factor
      receptors in a human lens epithelial cell line.
AB  - PURPOSE: To investigate the effect of basic fibroblast growth factor (bFGF),
      epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), and
      transforming growth factor beta 2 (TGFbeta2) on proliferation of a human lens
      epithelial cell line (HLEC-SRA 01/04); the effect of bFGF and TGFbeta2 on
      proliferation of human lens epithelial cells (HLECs); and the expression of bFGF,
      EGF, IGF-1, and TGFbeta2 receptors in an HLEC-SRA 01/04 cell line. SETTING:
      Department of Ophthalmology, University of Ulm, Ulm, Germany. METHODS: Both HLEC
      and HLEC-SRA 01/04 were treated with 1 to 50 ng/mL bFGF and TGFbeta2)
      Additionally, HLEC-SRA 01/04 were cultured with EGF and IGF-1 at a concentration
      of 1 to 50 ng/mL for 48 hours in the presence of [3H]-thymidine. In all
      experiments, untreated serum-free negative controls were used. (3H)-thymidine
      incorporation as a direct measure of lens epithelial cell proliferation was
      assessed by liquid scintillation counting. The expression of bFGF, EGF, IGF-1,
      and TGFbeta2 receptors in HLEC-SRA 01/04 were analyzed by reverse transcriptase
      polymerase chain reaction (RT-PCR). Statistical analysis was performed using the
      2-sample t test for the means. RESULTS: Proliferation of HLECs was dose
      dependently induced by bFGF and TGFbeta2, showing maximum effects at 10 ng/mL (P
      = .0003) and at 50 ng/mL (P < .0001), respectively. Proliferation of HLEC-SRA
      01/04 was also induced by bFGF, showing slight but significant effects (P < .03).
      Additionally, HLEC-SRA 01/04 proliferation was dose-dependently induced by EGF
      with a maximum effect at 5 ng/mL (P < .01), IGF-1 with a maximum effect at 5
      ng/mL (P < .0001), and TGFbeta2 with a maximum effect at 10 ng/mL (P < .0001)
      compared with the control. The RT-PCR analysis revealed bFGF, EGF, IGF-1, and
      TGFbeta2 receptor expression in the HLEC-SRA 01/04 cell line. CONCLUSIONS: The
      data showed that bFGF and TGFbeta2 are strong mitogens for HLEC. The HLEC-SRA
      01/04 cell line derived from HLEC reacted to growth factors, with cell
      proliferation only to a lesser extent. Such quiescence of these cells, when
      compared with cells in primary culture, cannot be explained by the lack of
      respective receptors for growth factors. Further investigation of growth factor
      induced responses of both cell types will provide new insight into the
      proliferative processes involved in postoperative secondary cataract formation.

PMID- 16631067
TI  - Fourth-generation fluoroquinolone-resistant bacterial keratitis after refractive
      surgery.
AB  - We report the first 2 cases of bacterial keratitis resistant to fourth-generation
      fluoroquinolones after laser in situ keratomileusis (LASIK) and photorefractive
      keratectomy (PRK). The first patient had Pseudomonas aeruginosa keratitis after
      PRK despite treatment with moxifloxacin. The second patient was on gatifloxacin
      post-LASIK when she had methicillin-resistant Staphylococcus aureus (MRSA)
      keratitis diagnosed. In both cases, culture susceptibilities showed isolates
      resistant to moxifloxacin and gatifloxacin, and treatment with topical
      aminoglycosides and surgical intervention was necessary to effect a cure. These
      cases show the potential limitations in the coverage of these antibiotics.

PMID- 16631068
TI  - Pseudomonas keratitis after laser in situ keratomileusis.
AB  - We report a 32-year-old woman who presented with infectious keratitis in the
      right eye 3 weeks after laser in situ keratomileusis (LASIK). On microbiological
      investigations, the microorganism isolated was Pseudomonas aeruginosa that was
      sensitive to ciprofloxacin. To our knowledge, this is the only case report in the
      literature of post-LASIK infectious keratitis caused by P aeruginosa.

PMID- 16631069
TI  - Propionibacterium acnes DNA from an explanted intraocular lens detected by
      polymerase chain reaction in a case of chronic pseudophakic endophthalmitis.
AB  - We report a case of Propionibacterium acnes DNA from the explanted intraocular
      lens (IOL) a 76-year-old man with delayed-onset chronic endophthalmitis. The
      detection was by polymerase chain reaction (PCR). Slitlamp microscopic
      examination showed cells and flare in the anterior chamber, keratic precipitates
      on the endothelium, and multiple white plaques on both surfaces of the IOL.
      Propionibacterium acnes DNA was found in both the aqueous humor and the explanted
      IOL by PCR. Scanning electron microscopy showed diphtheroid particles, a coating
      of biofilm-like deposits, as well as scattered crystals on the surface of the
      explanted IOL and supported the possibility of P acne colonies on the IOL.

PMID- 16631070
TI  - Bilateral Artisan lens for aphakia and megalocornea: Long-term follow-up.
AB  - We received approval from the U.S. implant Food and Drug Administration and the
      University's Institutional Review Board to the Artisan lens (Ophtec BV) in both
      eyes of a patient who was aphakic and had megalocornea. No other intraocular lens
      would easily solve this patient's need because of the large anterior segment. The
      patient was having increasing difficulty with aphakic contact lenses because of
      his work environment. We present almost 5 years of follow-up data of this
      patient.

PMID- 16631071
TI  - Comatic aberration as a cause of monocular diplopia.
AB  - Three patients (5 eyes) presented with complaints of monocular diplopia and no
      history of ocular trauma or surgery. The patients had comprehensive
      neuroophthalmic evaluation including manifest refraction, anterior segment and
      dilated fundus examination, and corneal topography. All patients also had
      wavefront analysis using the LADARWave system (Alcon). Two patients (4 eyes) also
      had hard contact lens overrefraction. The patients had a normal initial
      examination including corneal topography. One patient (2 eyes) did not experience
      resolution of diplopia with pinhole. No eye improved with manifest refraction or
      hard contact lens overrefraction. However, each patient had a significant amount
      of coma on wavefront analysis. Moreover, eyes with horizontal diplopia had
      horizontal coma and eyes with vertical diplopia had vertical coma as measured
      with the wavefront device. Higher-order optical aberrations such as coma may be
      associated with monocular diplopia. Wavefront technology may be useful in the
      workup of monocular diplopia.

PMID- 16631072
TI  - Surgical management of late dislocated lens capsular bag with intraocular lens
      and endocapsular tension ring.
AB  - A case of late spontaneous dislocation of the lens capsular bag (CB) with
      foldable acrylic intraocular lens (IOL) and endocapsular tension ring (CTR) and
      its surgical management is reported in a 52-year-old man. The dislocation
      occurred 2 years 3 months after phacoemulsification cataract surgery in which a
      CTR was used for zonular instability. A 3-port pars plana vitrectomy was
      performed. Because it was not possible to grasp the IOL-CTR-CB complex,
      perfluorocarbon liquid was used to attempt to float it up. This was unsuccessful,
      so a scleral indenter was used to apply external pressure on the sclera to tilt
      the IOL-CTR-CB complex into a position where it could be grasped with a forceps
      and removed through a corneal section. A scleral-fixated IOL was placed, and the
      patient achieved a best corrected visual acuity of 6/9. The procedure was safe
      and effective without intraocular complications.

PMID- 16631073
TI  - Retinal detachment after laser refractive surgery at the Singapore National Eye
      Centre.

PMID- 16631074
TI  - Coma-like wavefront artifact induced by a posterior staphyloma and high
      refractive error.

PMID- 16631075
TI  - Survey of neodymium:YAG laser posterior capsulotomy practice in the United
      Kingdom.

PMID- 16631076
TI  - O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications.
AB  - O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has
      demonstrated convincing results especially in the diagnostics of brain tumors. In
      contrast to other radiolabeled amino acids, it can be produced with high
      efficiency and distributed in a satellite concept like the widely used 2
      [18F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it
      shows high uptake in cerebral gliomas and in extracranial squamous cell
      carcinomas owing to increased transport. The tracer exhibits high in vivo
      stability, low uptake in inflammatory tissue and suitable uptake kinetics for
      clinical imaging, which indicates that it may become a new standard tracer for
      PET. In this article, the present knowledge on the uptake mechanisms and the
      clinical applications of FET are reviewed and the clinical perspectives are
      discussed.

PMID- 16631077
TI  - Nicotinic alpha4beta2 receptor imaging agents: part II. Synthesis and biological
      evaluation of 2-[18F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene)
      in rodents and imaging by PET in nonhuman primate.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) has been implicated in
      various neurodegenerative diseases. Optimal positron emission tomography (PET)
      imaging agents are therefore highly desired for this receptor. We report here the
      development and initial evaluation of 2-fluoro-3-[2-((S)-3
      pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat
      brain homogenate using 3H-cytisine exhibited a K(i) = 0.50 nM for the alpha4beta2
      sites. The radiosynthesis of 2-18F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine
      (18F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40
      50%, decay corrected. The specific activity was estimated to be approx. 37-185
      GBq/micromol. In vitro autoradiography in rat brain slices indicated selective
      binding of 18F-nifene to anteroventral thalamic (AVT) nucleus, thalamus,
      subiculum, striata, cortex and other regions consistent with alpha4beta2 receptor
      distribution. Rat cerebellum showed some binding, whereas regions in the
      hippocampus had the lowest binding. The highest ratio of >13 between AVT and
      cerebellum was measured for 18F-nifene in rat brain slices. The specific binding
      was reduced (>95%) by 300 microM nicotine in these brain regions. Positron
      emission tomography imaging study of 18F-nifene (130 MBq) in anesthetized rhesus
      monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed
      selective maximal uptake in the regions of the anterior medial thalamus, ventro
      lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including
      the subiculum. The cerebellum in the monkeys showed lower binding than the other
      regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a
      value of 2.2 and subsequently reduced. The faster binding profile of 18F-nifene
      indicates promise as a PET imaging agent and thus needs further evaluation.

PMID- 16631078
TI  - In vitro evaluation of nicotinic acetylcholine receptors with 2-[18F]F-A85380 in
      Parkinson's disease.
AB  - Nicotinic acetylcholine receptors (nAChR) are involved in many physiological
      functions and appear to be affected in neurodegenerative diseases like
      Alzheimer's disease and Parkinson's disease (PD). Here, we describe the in vitro
      evaluation of nAChRs in PD with 2-[18F]F-A85380, a ligand with high affinity to
      the beta2 nAChR subunit. Autoradiography with 2-[18F]F-A85380 in untreated rat
      brain corresponded to the known distribution of alpha4beta2 nAChRs with high
      uptake in the thalamus, moderate uptake in the striatum and cortex and low uptake
      in the cerebellum (47%, 43% and 19% of the thalamus, respectively). The
      localization of alpha4beta2 nAChRs in the striatum was investigated in rodents
      with unilateral lesion of the substantia nigra. 2-[18F]F-A85380 binding was
      significantly reduced in the striatum ipsilateral to the lesion side (to 64% of
      the contralateral side), indicating that a fraction of alpha4beta2 nAChRs is
      located on dopaminergic terminals, whereas another fraction resides on striatal
      interneurons or cortical afferents. Similarly, in human brain sections of PD
      patients, 2-[18F]F-A85380 uptake was significantly reduced not only in the
      caudate and putamen but also in the thalamus (approximately 30% of the binding of
      control brain in all three regions); within the striatum, nAChRs in the putamen
      were significantly more severely affected as in the caudate. The observed pattern
      of alpha4beta2* nAChR loss demonstrates the potential of 2-[18F]F-A85380 for
      further investigations of this positron emission tomography ligand for in vivo
      studies of alpha4beta2* nAChRs in PD.

PMID- 16631079
TI  - Synthesis and evaluation of [125I]I-TSA as a brain nicotinic acetylcholine
      receptor alpha7 subtype imaging agent.
AB  - INTRODUCTION: Some in vitro investigations have suggested that the nicotinic
      acetylcholine receptor (nAChR) alpha7 subtype is implicated in Alzheimer's
      disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen
      2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin]-2'-one (Br-TSA),
      which has a high affinity and selectivity for alpha7 nAChRs. Therefore we
      synthesized (R)-3'-(5-[125I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane
      3,5'-[1',3']oxazolidin]-2'-one ([125I]I-TSA) and evaluated its potential for the
      in vivo detection of alpha7 nAChR in brain. METHODS: In vitro binding affinity of
      I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by
      a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail
      vein injection of [(125)I]I-TSA. In vivo receptor blocking studies were carried
      out by treating mice with methyllycaconitine (MLA; 5 nmol/5 mul, i.c.v.) or
      nonradioactive I-TSA (50 micromol/kg, i.v.). RESULTS: I-TSA exhibited a high
      affinity and selectivity for the alpha7 nAChR (K(i) for alpha7 nAChR = 0.54 nM).
      Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance
      of radioactivity was relatively slow in the hippocampus (alpha7 nAChR-rich
      region) and was rather rapid in the cerebellum (alpha7 nAChR poor region). The
      hippocampus to cerebellum uptake ratio was 0.9 at 5 min postinjection, but it was
      increased to 1.8 at 60 min postinjection. Although the effect was not
      statistically significant, administration of I-TSA and MLA decreased the
      accumulation of radioactivity in hippocampus. CONCLUSION: Despite its high
      affinity and selectivity, [125I]I-TSA does not appear to be a suitable tracer for
      in vivo alpha7 nAChR receptor imaging studies due to its high nonspecific
      binding. Further structural optimization is needed.

PMID- 16631080
TI  - Inhibition of serotonin transport by (+)McN5652 is noncompetitive.
AB  - INTRODUCTION: Imaging of the serotonergic innervation of the brain using positron
      emission tomography (PET) with the serotonin transporter (SERT) ligand [11C]
      (+)McN5652 might be affected by serotonin in the synaptic cleft if there is
      relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim
      of the present study therefore was to pharmacologically characterize the
      interaction of [11C] (+)McN5652 and serotonin at the SERT. METHODS: In vitro
      saturation analyses of [3H]serotonin uptake into HEK293 cells stably expressing
      the human SERT were performed in the absence and presence of unlabelled
      (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. RESULTS:
      Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin
      transport V(max) of SERT without affecting the Michaelis-Menten constant K(M).
      CONCLUSIONS: This finding indicates that (+)McN5652 inhibits serotonin transport
      through the SERT in a noncompetitive manner. This might suggest that [11C]
      (+)McN5652 PET is not significantly affected by endogenous serotonin.

PMID- 16631081
TI  - Effects of anpirtoline on regional serotonin synthesis in the rat brain: an
      autoradiographic study.
AB  - Anpirtoline has been described as an agonist at 5-HT1B receptors with a
      relatively high potency. It also acts as an agonist at 5-HT1A receptors, but has
      a lower potency than at the 5-HT1B sites. There is very little known about the
      mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the
      present study was to investigate the effects of acutely and chronically
      administered anpirtoline on 5-HT synthesis in the rat brain using the
      autoradiographic alpha-[14C]methyl-L-tryptophan method. In the acute study,
      anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the
      tracer injection. The control rats were injected with the same volume of saline.
      In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously
      in saline once a day for 10 days. There were no significant differences between
      the plasma-free and total tryptophan concentrations between the anpirtoline
      treatment and the respective control groups. In the acute experiment, 5-HT
      synthesis rates in all of the brain areas investigated were significantly
      decreased by anpirtoline when compared to the saline-treated group. In the
      chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the
      projection areas, as well as the raphe nuclei, were normalized or had a tendency
      to be normalized. These results suggest that it is likely that the terminal 5
      HT1B receptors are involved in the regulation of 5-HT synthesis in the projection
      areas and that 5-HT synthesis, in the raphe, is likely influenced by
      anpirtoline's 5-HT1A and/or 5-HT1B agonistic properties.

PMID- 16631082
TI  - In vitro cytotoxicity of 211At-labeled trastuzumab in human breast cancer cell
      lines: effect of specific activity and HER2 receptor heterogeneity on survival
      fraction.
AB  - INTRODUCTION: Radioimmunotherapy with anti-HER2 monoclonal antibodies (mAbs) such
      as trastuzumab is a promising strategy for treating HER2-positive breast and
      ovarian carcinoma patients. The objective of this study was to determine the
      cytotoxic effectiveness of trastuzumab labeled with the 7.2-h half-life alpha
      particle emitter 211At. METHODS: Experiments were performed on SKBr-3, BT-474 and
      the transfected MCF7/HER2-18 human breast carcinoma cell lines. Intrinsic
      radiosensitivity was determined after exposure to external beam irradiation. The
      cytotoxicity of 211At-labeled trastuzumab was measured by clonogenic assays. The
      distribution of HER2 receptor expression on the cell lines was measured using
      fluorescence-activated cell sorting. A pharmacokinetic (PK)/microdosimetric model
      was established to assess the effects of specific activity (SA), HER2 receptor
      expression and absorbed dose on survival fraction (SF). RESULTS: With external
      beam irradiation, the 2-Gy SF for BT-474, SKBr-3 and MCF7/HER2-18 cells was 0.78,
      0.53 and 0.64 Gy, respectively. Heterogeneous HER2 expression was observed, with
      a subpopulation of cells lacking measurable receptor (14.5%, SKBr-3; 0.34%, MCF
      7/HER2; 1.73%, BT-474). When plotted as a function of activity concentration, SF
      curves were biphasic and inversely proportional to SA; however, when the model
      was applied and absorbed doses calculated, the SF curve was monoexponential
      independent of SA. Thus, the PK model was able to demonstrate the effects of
      competition between cold and labeled mAb. These studies showed that the relative
      biological effectiveness of 211At-labeled trastuzaumab was about 10 times higher
      than that of external beam therapy. CONCLUSION: These in vitro studies showed
      that 211At-labeled trastuzumab mAb is an effective cytotoxic agent for the
      treatment of HER2-positive tumor cells. The SA of the labeled mAb and the
      homogeneity of HER2 receptor expression are important variables influencing the
      efficiency of cell killing.

PMID- 16631083
TI  - Dual optical and nuclear imaging in human melanoma xenografts using a single
      targeted imaging probe.
AB  - INTRODUCTION: Dual-labeled imaging agents that allow both nuclear and optical
      imaging after a single injection would be advantageous in certain applications.
      In this study, we synthesized and characterized a dual-labeled RGD (Arg-Gly-Asp)
      peptide and compared nuclear and optical images obtained with this agent.
      METHODS: 111In-DTPA-Lys(IRDye800)-c(KRGDf) composed of both the 111In chelator
      diethylenetriaminepentaacetic acid (DTPA) and the near-infrared (NIR) fluorescent
      dye IRDye800 (excitation/emission, 765/792 nm) was synthesized. The probe was
      characterized with regard to in vitro biological activity and in vivo
      pharmacokinetics and the ability to target integrin alphavbeta3. Tumors of mice
      injected with the dual-labeled probe were imaged both by gamma scintigraphy and
      NIR fluorescence optical camera. RESULTS: DTPA-Lys(IRDye800)-c(KRGDf), DTPA-Lys
      c(KRGDf) and c(KRGDf) inhibited the adhesion of melanoma M21 cells to vitronectin
      coated surface with the similar biological activity. Both 111In-DTPA
      Lys(IRDye800)-c(KRGDf) and 111In-DTPA-Lys-c(KRGDf) had significantly higher
      uptakes in alphavbeta3-positive M21 melanoma than in alphavbeta3-negative M21-L
      melanoma at 4-48 h after their injection. Side-by-side comparison of images
      obtained using 111In-DTPA-Lys(IRDye800)-c(KRGDf) revealed that in living mice,
      both optical imaging and gamma scintigraphy enabled noninvasive detection of the
      bound probe to alphavbeta3-positive tumors, with optical images providing
      improved resolution and sensitive detection of the superficial lesions and gamma
      images providing sensitive detection of deeper structures. CONCLUSION: The dual
      labeled imaging probe 111In-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically
      bind to alphavbeta3 in melanoma tumor cells. Employing both nuclear and optical
      imaging with a single imaging probe may facilitate translation of NIR
      fluorescence optical imaging into clinical applications.

PMID- 16631084
TI  - Synthesis and evaluation of a radiometal-labeled macrocyclic chelator-derivatised
      thymidine analog.
AB  - Several radiolabeled thymidine analogs as metabolic probes of cell proliferation
      were developed specifically addressing DNA synthesis. Thymidine analogs
      containing carboranylalkyl groups for neutron capture therapy at the N-3 position
      were found to be good substrates for cytosolic thymidine kinase 1 (TK1).
      According to this approach, a DO3A macrocycle in N-3 position was attached to
      thymidine. The 3-DO3A thymidine analog was labeled with 68Ga and 111In. Different
      lipophilicities of the corresponding radiometal-thymidines were detected via RP
      HPLC. [111In]DO3A-thymidine ([111In]D3T) was evaluated for cellular uptake in
      different cell lines (HL60 and DoHH2). Cellular uptake was low in both cell
      lines. Phosphorylation of the radioconjugates by TK1 was negligible. Although
      stable complexation of radiometals to thymidine was obtained, introduction of the
      macrocycle DO3A reduced the affinity to cytosolic TK1 drastically. Low cellular
      uptake can be ascribed to missing substrate specificity of [111In]DO3A-thymidine
      for TK1. The absence of substrate specificity may be due to the bulky macrocyclic
      chelator and partial charges remaining on the coordination sphere due to a more
      complex solution structure.

PMID- 16631085
TI  - Synthesis of 5-radioiodoarabinosyl uridine analog for probing HSV-1 thymidine
      kinase gene: an unexpected chelating effect.
AB  - Tumor cells transduced with herpes simplex virus thymidine kinase gene has been
      intensively applied to the field of positron emission tomography via imaging of
      its substrate. As a pilot synthesis approach, a facial preparation of 5
      [125I]iodoarabinosyl uridine starting from commercial available uridine is
      reported herein. Interestingly, the tin group in 5-trimethylstannyl
      arabinosyluridine was easily removed during purification. The destannylation
      through the formation of a six-ligand coordination involving 2'-hydroxyl and tin
      was thereby proposed.

PMID- 16631086
TI  - Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs
      in a mouse model of human prostate adenocarcinoma.
AB  - Bombesin (BBN), an analog of human gastrin-releasing peptide (GRP), binds to the
      GRP receptor (GRPR) with high affinity and specificity. Overexpression of GRPR
      has been discovered in mostly androgen-independent human prostate tissues and,
      thus, provides a potential target for prostate cancer diagnosis and therapy. We
      have previously demonstrated the feasibility of the positron emission tomography
      (PET) imaging using 64Cu-1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid
      (DOTA)-[Lys3]BBN to detect GRPR-positive prostate cancer. In this study, we
      compared the receptor affinity, metabolic stability, tumor-targeting efficacy,
      and pharmacokinetics of a truncated BBN analog 64Cu-DOTA-Aca-BBN(7-14) with 64Cu
      DOTA-[Lys3]BBN. Binding of each DOTA conjugate to GRPR on PC-3 and 22Rv1 prostate
      cancer cells was evaluated with competitive binding assay using 125I-[Tyr4]BBN as
      radioligand. In vivo pharmacokinetics was determined on male nude mice
      subcutaneously implanted with PC-3 cells. Dynamic microPET imaging was performed
      to evaluate the systemic distribution of the tracers. Metabolic stability of the
      tracers in blood, urine, tumor, liver and kidney was studied using high
      performance liquid chromatography. The results showed that 125I-[Tyr4]BBN has a
      K(d) of 14.8+/-0.4 nM against PC-3 cells, and the receptor concentration on PC-3
      cell surface is approximately 2.7+/-0.1 x 10(6) receptors per cell. The 50%
      inhibitory concentration value for DOTA-Aca-BBN(7-14) is 18.4 +/- 0.2 nM, and
      that for DOTA-[Lys3]BBN is 2.2 +/- 0.5 nM. DOTA-[Lys3]BBN shows a better tumor
      contrast and absolute tumor activity accumulation compared to DOTA-Aca-BBN(7-14).
      Studies on metabolic stability for both tracers on organ homogenates showed that
      64Cu-DOTA-[Lys3]BBN is relatively stable. This study demonstrated that both
      tracers are suitable for targeted PET imaging to detect the expression of GRPR in
      prostate cancer, while 64Cu-DOTA-[Lys3]BBN may have a better potential for
      clinical translation.

PMID- 16631087
TI  - (99m)Tc complexes with activated ester functions; ligands comprising a 3,4
      diamino-benzoate backbone.
AB  - Preformed (99m)Tc chelates with an activated ester function are useful for the
      gentle labeling of proteins (precomplexation route). In this context, new
      heterobifunctional ligands derived from 2,3,5,6-tetrafluorophenyl (TFP) 3,4
      diamino-benzoates (OC1, OC3, OC4) were synthesized. Their corresponding (99m)Tc
      complexation and protein-conjugation characteristics were elucidated and compared
      with the results previously reported using 2,3,5,6-tetrafluorophenyl N-(S
      benzoylthioacetyl)glycylglycyl-p-aminobenzoate (OC2). The reaction temperatures
      and the reaction time markedly influenced complexation yields. Compared with OC2,
      the (99m)Tc-chelate formation with OC1 and OC4 was more effective, showing
      radiochemical yields of 60% and 70% within 20 min, respectively. Owing to steric
      hindrance, the complexation of OC3, however, did not exceed 10%. No-carrier-added
      (99m)Tc complexes were conjugated at pH 10 with the anti-EGF-receptor monoclonal
      antibody MAb425, resulting in labeling yields of 14% for (99m)Tc-OC1 and 7% for
      (99m)Tc-OC4 after incubating for 20 min at 30 degrees C. Increasing the
      temperature to 40 degrees C improved these results by 14% and 3%, respectively.
      As compared with (99m)Tc-OC2, which provides the chelating substituent at the 4
      phenyl position only, the application of 3,4-phenyl substituents proved less
      appropriate for protein conjugation. However, the 3,4-diaminobenzoate backbone
      may be attractive for an alternative design of novel (99m)Tc N2S2 or N3S
      complexes, because they show excellent complexation characteristics.

PMID- 16631088
TI  - Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use
      in noninvasive radiological imaging of therapeutic gene transfer.
AB  - INTRODUCTION: Noninvasive analysis of therapeutic transgene expression is
      important for the development of clinical translational gene therapy strategies
      against cancer. To image p53 and MnSOD gene transfer noninvasively, we used
      radiologically detectable dual-expressing adenoviral vectors with the human
      sodium iodide symporter (hNIS) as the reporter gene. METHODS: Dual-expressing
      adenoviral vectors were constructed with hNIS cloned into E3 region and
      therapeutic genes, either MnSOD or p53, recombined into the E1 region. Steady
      state mRNA levels of hNIS were evaluated by real-time polymerase chain reaction.
      hNIS function was determined by iodide uptake assay and MnSOD, and p53 protein
      levels were assessed by Western blots. RESULTS: 125I- accumulation resulting from
      hNIS expression in both Ad-p53-hNIS- and Ad-MnSOD-hNIS-infected MDA-MB-435 cells
      could be visualized clearly on phosphorimaging autoradiograph. Iodide
      accumulation increased with increasing adenovirus titer, and there was a linear
      correlation between iodide uptake and dose. p53 and MnSOD protein levels
      increased as a function of adenovirus titer, and there was a direct positive
      correlation between p53 and MnSOD expression and hNIS function. P53 and MnSOD
      overexpression inhibited cell growth in the dual-expressing adenoviral vector
      infected cells. CONCLUSIONS: Radiological detection of hNIS derived from dual
      expressing adenoviral vectors is a highly effective method to monitor therapeutic
      gene transfer and expression in a noninvasive manner.

PMID- 16631089
TI  - Molecular imaging of alkylguanine-DNA alkyltransferase: further evaluation of
      radioiodinated derivatives of O6-benzylguanine.
AB  - PURPOSE: An inverse correlation has been established between tumor levels of the
      DNA repair protein alkylguanine-DNA alkyltransferase (AGT) and a positive outcome
      after alkylator chemotherapy. Quantitative imaging of AGT could provide important
      information for patient-specific cancer treatment. Several radiolabeled analogues
      of O6-benzylguanine (BG), a potent AGT inactivator, have been developed and shown
      to be capable of labeling pure AGT protein. Herein, two of these analogues--O6-3
      [*I]iodobenzylguanine ([*I]IBG) and O6-3-[*I]iodobenzyl-2'-deoxyguanosine
      ([*I]IBdG)--were further evaluated in two murine xenograft models. (AcO)2
      [131I]IBdG, a peracetylated derivative of IBdG, also was investigated as an
      alternative agent. METHODS: Several biodistribution studies of radioiodinated IBG
      and IBdG were performed in TE-671 human rhabdomyosarcoma and DAOY human
      medulloblastoma murine xenograft models. Mice were treated with BG or its
      nucleoside analogue dBG to deplete the tumor AGT content. The effect of unlabeled
      IBG and that of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-450
      isozyme CYP1A2, on the tumor uptake of the tracers was determined. The uptake of
      (AcO)2-[131I]IBdG along with that of [125I]IBdG in DAOY cells in vitro was
      determined in the presence and absence of a nucleoside transporter inhibitor,
      dipyridamole. RESULTS: Pretreatment of mice either with BG or dBG failed to
      reduce tumor levels of [*I]IBG or [*I]IBdG even though such treatments completely
      depleted tumor AGT content. Treatment of mice with BF increased tumor uptake of
      [125I]IBG by 56%; however, differentiation of tumors with and without AGT still
      was not possible. (AcO)2-[131I]IBdG, a peracetylated derivative of IBdG, had a
      higher uptake in vitro in DAOY tumor cells. However, its uptake, like that of
      [125I]IBdG, was blocked by dipyridamole. CONCLUSIONS: Taken together, these
      results suggest that labeled agents that are more specific for cellular AGT and
      that are more metabolically stable are needed.

PMID- 16631090
TI  - Repeated administration of D-amphetamine induces loss of [123I]FP-CIT binding to
      striatal dopamine transporters in rat brain: a validation study.
AB  - In recent years, several PET and SPECT studies have shown loss of striatal
      dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use
      of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been
      validated. We therefore examined if repeated administration of D-AMPH or
      methamphetamine (METH) may induce loss of binding to striatal DATs in rats by
      using an experimental biodistribution study design and a SPECT tracer for the DAT
      ([123I]FP-CIT). METHODS: Groups of male rats (n = 10 per group) were treated with
      D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a
      day for 5 consecutive days. Five days later, [123I]FP-CIT was injected
      intravenously, and 2 h later, the rats were sacrificed and radioactivity was
      assayed. RESULTS: In d-AMPH but not METH-treated rats, striatal [123I]FP-CIT
      uptake was significantly lower (approximately 17%) than in the control group.
      CONCLUSION: These data show that [123I]FP-CIT can be used to detect AMPH-induced
      changes in DAT binding and may validate the use of DAT radiotracers to study AMPH
      induced changes in striatal DAT binding in vivo.

PMID- 16631091
TI  - Evaluation of (99m)Tc-labeled tropanes with alkyl substituents on the 3beta
      phenyl ring as potential dopamine transporter tracers.
AB  - Technetium(V)-oxo-3beta-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl[N
      (2-mercaptoethyl), N-(N'-(2-mercaptoethyl)-2-aminoethyl)]-aminomethyl ((99m)Tc
      TRODAT-1) and three derivatives with one or two substituents on the 3beta-phenyl
      ring (4-methylphenyl, 4-ethylphenyl and 2,4-dimethylphenyl) were prepared and
      evaluated as potential imaging agents for the central nervous dopamine
      transporter (DAT). Labeling of the ligands with (99m)Tc yielded for each of them
      a mixture of two radiolabeled species, which were purified and isolated using
      reversed-phase high-performance liquid chromatography. Employing radio-LC-MS, we
      found both species to have the same molecular mass suggesting diastereoisomers.
      After intravenous injection in mice and rats, the compounds were stable in vivo
      and no important metabolites were found in plasma or urine. Replacement of the 4
      chloro atom on the 3beta-phenyl ring by a methyl group causes no loss of affinity
      for the DAT system. However, substitution of an ethyl group for the 4-chloro atom
      or introduction of a second methyl group in the 2-position of the phenyl ring
      results in a serious reduction of the affinity for the DAT transporter. Ex vivo
      autoradiography on mice brain slices and biodistribution studies in rats showed
      specific uptake of (99m)Tc-TRODAT-1 and the 4-methylphenyl derivative in striatum
      and putamen. Although the 4-ethylphenyl and 2,4-dimethylphenyl derivatives show
      brain uptake in rats and mice, no specific uptake in striatum was found. In
      addition, differences in biological behavior between the different diastereomers
      were observed. In conclusion, small changes to (99m)Tc-TRODAT-1 at the phenyl
      ring in the 3beta position of the tropane moiety significantly change the
      biological behavior of the studied compounds.

PMID- 16631092
TI  - Evaluation of novel cationic (99m)Tc-nitrido complexes as radiopharmaceuticals
      for heart imaging: improving liver clearance with crown ether groups.
AB  - This report describes the evaluation of a series of novel cationic (99m)Tc
      nitrido complexes, [(99m)TcN(DTC)(PNP)]+ (DTC = crown ether-containing
      dithiocarbamates; PNP = bisphosphine), as potential radiotracers for myocardial
      perfusion imaging. Synthesis of cationic (99m)Tc-nitrido complexes was
      accomplished in two steps according to literature methods. Biodistribution
      studies were performed in rats. Planar images of Sprague-Dawley rats administered
      with 15+/-2 MBq of cationic (99m)Tc radiotracer were obtained using a PhoGama
      large field-of-view Anger camera. Samples from both urine and feces were analyzed
      by a reversed-phase radio-HPLC method. Results from biodistribution studies
      showed that most of the cationic (99m)Tc-nitrido complexes have a high initial
      heart uptake with a long myocardial retention. They also show a rapid clearance
      from the liver and lungs. Cationic complexes [(99m)TcN(L2)(L6)]+ and
      [(99m)TcN(L4)(L6)]+ show heart/liver ratios four to five times better than that
      of (99m)Tc-sestamibi due to their much faster liver clearance. Their heart uptake
      and heart/liver ratio are comparable to that of (99m)TcN-DBODC5 within the
      experimental error. These findings have been confirmed by the results from
      imaging studies. Radio-HPLC analysis of urine and feces samples indicated that
      there was very little metabolism of cationic (99m)Tc-nitrido complexes in rats
      under anesthesia. The key finding of this study is that lipophilicity remains the
      most important factor affecting both heart uptake and target-to-background (T/B)
      ratios. Crown ethers are very useful functional groups to improve the liver
      clearance of cationic (99m)Tc-nitrido complexes. It is the combination of the
      appropriate DTCs and bisphosphines that results in cationic (99m)Tc-nitrido
      complexes with high heart uptake and fast clearance from the liver at the same
      time. The fast liver clearance of [(99m)TcN(L2)(L6)]+ and [(99m)TcN(L4)(L6)]+
      suggests that they might be used to obtain clinically useful images as early as
      30 min postinjection. [(99m)TcN(L2)(L6)]+ and [(99m)TcN(L4)(L6)]+ are very
      promising candidates for further evaluation in more extensive preclinical animal
      models.

PMID- 16631093
TI  - Neutrophil labeling with [(99m)Tc]-technetium stannous colloid is complement
      receptor 3-mediated and increases the neutrophil priming response to
      lipopolysaccharide.
AB  - INTRODUCTION: [(99m)Tc]-technetium stannous colloid (TcSnC)-labeled white cells
      are used to image inflammation. Neutrophil labeling with TcSnC is probably
      phagocytic, but the phagocytic receptor involved is not known. We hypothesised
      that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could
      theoretically result in neutrophil activation or priming, affecting the behaviour
      of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter
      measurements can assess neutrophil activation and priming. METHODS: We tested
      whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil
      uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the
      CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered
      activation or priming status, comparing FACS side scatter in labeled and
      unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a
      known priming agent. RESULTS: Anti-CD11b mAb reduced neutrophil uptake of TcSnC
      in a dose-dependent fashion. Labeled neutrophils did not show significantly
      increased side scatter compared to controls. LPS significantly increased side
      scatter in control cells and labeled neutrophils. However, the increase was
      significantly greater in labeled neutrophils than unlabeled cells. CONCLUSIONS:
      Neutrophil labeling with TcSnC is related to the function of CR3, a receptor
      which plays a central role in phagocytosis. TcSnC labeling did not significantly
      activate or prime neutrophils. However, labeled neutrophils showed a greater
      priming response to LPS. This could result in labeled neutrophils demonstrating
      increased adhesion on activated endothelium at sites of infection.

PMID- 16631094
TI  - Quality control of PET radiopharmaceuticals using HPLC with electrochemical
      detection.
AB  - The usefulness of high-performance liquid chromatography with electrochemical
      detection (HPLC/ECD) in the quality control of positron emission tomography (PET)
      radiopharmaceuticals was evaluated for a number of substances. Chromatographic
      separation was performed using a reversed phase column and acetonitrile or 20 mM
      sodium phosphate buffer as the mobile phase. The effluent from the column was
      introduced into an electrochemical detector equipped with a glassy carbon
      electrode versus Ag/AgCl electrode operated in the direct current mode. In 19 of
      21 PET radiopharmaceuticals studied, the compounds and corresponding precursors
      used in the synthesis of the radiopharmaceuticals could be successfully detected
      by the HPLC/ECD method. For 17 compounds with electroactive functional groups,
      such as aliphatic amines, phenols and aromatic amines, the detection limits were
      ppb levels for a 20-mul injection volume; this was significantly better compared
      with ultraviolet (UV) detection. This method could be applied to the analysis of
      [11C]MP4A, useful PET radiopharmaceutical for measuring acetylcholinesterase
      activity in the brain with no available UV absorbance.

PMID- 16631096
TI  - Birth asphyxia in developing countries: current status and public health
      implications.

PMID- 16631097
TI  - Newborn immunology: relevance to the clinician.

PMID- 16631099
TI  - Cessation of asthma medication in early pregnancy.
AB  - OBJECTIVE: The objective of the study was to determine whether women alter their
      use of asthma medications during pregnancy. STUDY DESIGN: Weekly asthma
      medication use was determined from prescription claims data in a cohort of
      112,171 pregnant women aged 15 to 44 years who were continuously enrolled in the
      Tennessee Medicaid program prior to their singleton pregnancy and who delivered a
      singleton birth during 1995 to 2001. Change in asthma medication use was
      evaluated using generalized estimating equation analyses. RESULTS: Women with
      asthma significantly (P < or = 0.0005) decreased their asthma medication use from
      5 to 13 weeks of pregnancy. During the first trimester, there was a 23% decline
      in inhaled corticosteroid prescriptions, a 13% decline in short-acting beta
      agonist prescriptions, and a 54% decline in rescue corticosteroid prescriptions.
      CONCLUSIONS: Utilization of all categories of asthma medications decreased in
      early pregnancy, with the largest declines occurring for inhaled and rescue
      corticosteroids.

PMID- 16631100
TI  - Successful neonatal outcome in 2 cases of maternal persistent vegetative state
      treated in a labor and delivery suite.
AB  - Two cases of maternal vegetative state after motor vehicle accidents are
      presented. Aggressive support allowed the prolongation of both pregnancies into
      the third trimester without neonatal compromise. After initial medical
      stabilization in intensive care unit environments, both patients were treated in
      a labor and delivery setting with consultative supports from various
      subspecialists.

PMID- 16631101
TI  - Team-based work and work system balance in the context of agile manufacturing.
AB  - Manufacturing agility is the ability to prosper in an environment characterized
      by constant and unpredictable change. The purpose of this paper is to analyze
      team attributes necessary to facilitate agile manufacturing, and using Balance
      Theory as a framework, it evaluates the potential positive and negative impacts
      related to these team attributes that could alter the balance of work system
      elements and resulting "stress load" experienced by persons working on agile
      teams. Teams operating within the context of agile manufacturing are
      characterized as multifunctional, dynamic, cooperative, and virtual. A review of
      the literature relevant to each of these attributes is provided, as well as
      suggestions for future research.

PMID- 16631102
TI  - Serpin crystal structure and serpin polymer structure.
AB  - Serpins are a family of structurally homologous proteins having metastable native
      structures. As a result, a serpin variant destabilized by mutation(s) has a
      tendency to undergo conformational changes leading to inactive forms, e.g., the
      latent form and polymer. Serpin polymers are involved in a number of
      conformational diseases. Although several models for polymer structure have been
      proposed, the actual structure remains unknown. Here, we provide a comprehensive
      list of serpins, both free and in complexes, deposited in the Protein Data Bank.
      Our discussion focuses on structures that potentially can contribute to a better
      understanding of polymer structure.

PMID- 16631103
TI  - Alternatively spliced FGFR-1 isoforms differentially modulate endothelial cell
      activation of c-YES.
AB  - Ligand activation of fibroblast growth factor receptor-1 (FGFR-1) induces an
      angiogenic response following activation of multiple intracellular signaling
      substrates, including the Src family of nonreceptor tyrosine kinases (SFK).
      However, the direct association between FGFR-1 and SFK and the involvement of SFK
      in FGFR-1-dependent cell proliferation have been controversial. Structural
      variants of FGFR-1 are generated by alternative splicing which results in two
      major isoforms, containing either three (FGFR-1alpha) or two (FGFR-1beta)
      immunoglobulin-like domains in the extracellular region. To determine whether
      alternatively spliced FGFR-1 isoforms differentially activate SFK, we have
      examined FGF receptor-negative endothelial cells stably transfected with human
      cDNA encoding either FGFR-1alpha or FGFR-1beta. Transient activation of c-YES,
      the predominant SFK expressed in these endothelial cells, was restricted to FGFR
      1beta transfectants following exposure to acidic fibroblast growth factor (FGF
      1). Co-immunoprecipitation studies revealed that c-YES directly associated with
      FGFR-1beta. The Src homology (SH)2 domain (and not the SH3 domain) of c-YES was
      able to recognize tyrosine phosphorylated FGFR-1beta. FGFR-1beta-specific
      activation of c-YES was accompanied by its association with and activation of
      cortactin. FGF-1 treatment of both FGFR-1alpha and FGFR-1beta transfectants
      induced SFK-independent cellular proliferation and growth in low density
      cultures. At high density, under both anchorage-dependent and -independent
      conditions, FGF-1 failed to induce proliferation and growth of FGFR-1alpha
      transfectants. In contrast, FGF-1 induced proliferation, growth, and formation of
      cord-like structures in high density cultures of FGFR-1beta transfectants in an
      SFK-dependent manner. In vitro cord formation on Matrigel was restricted to FGFR
      1beta transfectants in an SFK-dependent manner. Formation of vascular structures
      in vivo was limited to endothelial cells transfected with FGFR-1beta.
      Collectively, these results emphasize the roles of alternatively spliced FGFR-1
      structural isoforms and activation of SFK as modulators of endothelial cell
      growth during the formation of neovascular structures.

PMID- 16631104
TI  - CG15031/PPYR1 is an intrinsically unstructured protein that interacts with
      protein phosphatase Y.
AB  - Protein phosphatase Y (PPY) is a Drosophila testis-specific enzyme of unknown
      function. In a yeast two-hybrid screen we identified CG15031/PPYR1 as a PPY
      interacting protein. The specificity of the protein-protein interaction was
      proven by directed two-hybrid tests. The complex formation between PPY and PPYR1
      was confirmed under in vitro and in vivo conditions by plasmon resonance
      spectroscopy, co-immunoprecipitation, and pull down experiments. Recombinant
      PPYR1 expressed in Escherichia coli is a heatstable, protease sensitive,
      intrinsically unstructured RNA-binding protein that migrates anomalously in SDS
      polyacrylamide gel electrophoresis. It can be phosphorylated by cAMP-dependent
      protein kinase in vitro. PPYR1 moderately inhibits PPY activity, the inhibitory
      potential of the protein is slightly increased by phosphorylation. We suggest
      that PPYR1 may function as a scaffolding protein that targets PPY to RNA and
      other protein partners in Drosophila melanogaster.

PMID- 16631105
TI  - Structural analogues of reactive intermediates as inhibitors of glucosamine-6
      phosphate synthase and phosphoglucose isomerase.
AB  - The active centers of phosphoglucose isomerase (PGI) and the hexose phosphate
      isomerase domain (HPI) of glucosamine-6-P (GlcN-6-P) synthase demonstrate
      apparent similarity in spatial arrangement of critical amino acid residues,
      except Arg272 of the former and Lys603 and Lys485 of the latter. Ten derivatives
      of d-hexitol-6-P, 5-phosphoarabinoate, or 6-phosphogluconate, structural
      analogues of putative cis-enolamine or cis-enolate intermediates, were tested as
      inhibitors of fungal GlcN-6-P synthase and PGI. None of the investigated
      compounds demonstrated equally high inhibitory potential against both enzymes. 2
      Amino-2-deoxy-D-mannitol 6-P was found to be the strongest GlcN-6-P synthase
      inhibitor in the series, with an inhibition constant equal to 9.0 (+/-1.0) x 10(
      6)M. On the contrary, 5-phosphoarabinoate (5PA) exhibited specificity for PGI,
      with K(i)=2.2 (+/-0.1) x 10(-6) M. N-acetylation substantially lowered the GlcN-6
      P synthase inhibitory potential of 2-amino-2-deoxy-D-glucitol-6-P but strongly
      enhanced inhibitory potential of this compound towards PGI. Molecular modeling
      studies revealed that interactions of the C1-C2 part of transition state analogue
      inhibitors with the respective areas demonstrating different distribution of
      molecular electrostatic potential (MEP) inside HPI and PGI active centers
      determined enzyme:ligand affinity. In Escherichia coli HPI, a patch of the
      negative potential created by Glu488 aided by Val399, supposed to stabilize a
      putative positively charged intermediate, especially attracts ligands containing
      2-amino function. The Arg272, Lys210, and Gly271 peptide bond nitrogen system,
      present in the corresponding space of rabbit PGI, creates an area of positive
      MEP, stabilizing cis-enolate intermediate and attracting its structural mimics,
      such as 5PA.

PMID- 16631106
TI  - Identification of Hsc70 binding sites in mitochondrial aspartate
      aminotransferase.
AB  - Hsc70 binds acid-unfolded mitochondrial aspartate aminotransferase (mAAT),
      forming either soluble or insoluble complexes depending on the relative
      concentrations of the proteins. Using partial proteolysis of Hsc70-mAAT complexes
      in combination with MALDI-TOF mass spectrometry, we have identified several
      potential Hsc70-binding regions in the mAAT polypeptide. Only one mAAT peptide
      was found bound to Hsc70 in the insoluble complexes while nine peptides arising
      from eight sequence regions of mAAT were found associated with Hsc70 in the
      soluble complexes. Most of these binding sites map to secondary structure
      elements, particularly alpha-helix, that are partly exposed on the surface of the
      folded structure. These results suggest that these peptide regions must not only
      be exposed but still in a flexible extended conformation in the mAAT folding
      intermediates recognized by Hsc70. Thus, for mAAT the discrimination between
      native and non-native structures by Hsc70 may rely more on the level of structure
      of the binding sites than on their degree of exposure to the solvent in the
      native structure.

PMID- 16631107
TI  - Energy deficiency in the failing heart: linking increased reactive oxygen species
      and disruption of oxidative phosphorylation rate.
AB  - Heart failure is a complex syndrome of numerous dysfunctional components which
      converge to cause chronic progressive failure of ventricular contractile function
      and maintenance of cardiac output demand. The aim of this brief review is to
      highlight some of the mounting evidence indicating that augmented superoxide,
      related reactive oxygen species and other free radicals contribute to the
      oxidative stress evident during the progression of heart failure. While much of
      the source of increased reactive oxygen species is mitochondrial, there are other
      intracellular sources, which together are highly reactive with functional and
      structural cellular lipids and proteins. Bioenergetic defects limiting ATP
      synthesis in the failing myocardium relate not only to post-translational
      modification of electron transport respiratory chain proteins but also to
      perturbation of Krebs Cycle enzyme-dependent synthesis of NADH. Accumulation of
      pathological levels of lipid peroxides relate to dysfunction in the intrinsic
      capacity to clear and renew dysfunctional proteins. This review also features key
      limitations of human heart failure studies and potential clinical therapies that
      target the elevated oxidative stress that is a hallmark of human heart failure.

PMID- 16631108
TI  - Influence of the chain length of ubiquinones on their interaction with DPPC in
      mixed monolayers.
AB  - The thermodynamic behavior of representative short (UQ2), middle (UQ4 and UQ6)
      and long-chain (UQ10) ubiquinones (UQ) mixed with dipalmitoyl-phosphatidylcholine
      (DPPC) was studied in monolayers at the air-water interface. The influence of
      isoprenoid chain-length of UQ on miscibility of both lipids was investigated by
      analysis of surface pressure-area isotherms and using fluorescence microscopy.
      Analysis of excess areas (A(ex)) and free energies of mixing (DeltaGm),
      calculated from compression isotherms in the full range of ubiquinones
      concentrations, has given evidences for UQ-rich constant-size (UQ6, UQ10) or less
      growth limited (UQ2, UQ4) microdomains formation within mixed films. Fluorescence
      microscopy observation revealed that ubiquinones are preferentially soluble in
      the expanded phase. When lateral pressure increased, concomitant evolutions of
      A(ex) and DeltaGm parameters, and composition dependence of collapse surface
      pressures, argue for an evolution towards a total segregation, never reached due
      to expulsion of ubiquinones from the film. The possible significance of these
      observations is discussed in relation to ubiquinones organization and similar
      chain length effects in membranes.

PMID- 16631109
TI  - Production and characterisation of recombinant forms of human pulmonary
      surfactant protein C (SP-C): Structure and surface activity.
AB  - Surfactant protein C (SP-C) is an essential component for the surface tension
      lowering activity of the pulmonary surfactant system. It contains a valine-rich
      alpha helix that spans the lipid bilayer, and is one of the most hydrophobic
      proteins known so far. SP-C is also an essential component of various surfactant
      preparations of animal origin currently used to treat neonatal respiratory
      distress syndrome (NRDS) in preterm infants. The limited supply of this material
      and the risk of transmission of infectious agents and immunological reactions
      have prompted the development of synthetic SP-C-derived peptides or recombinant
      humanized SP-C for inclusion in new preparations for therapeutic use. We describe
      herein the recombinant production in bacterial cultures of SP-C variants
      containing phenylalanines instead of the palmitoylated cysteines of the native
      protein, as fusions to the hydrophilic nuclease A (SN) from Staphylococcus
      aureus. The resulting chimerae were partially purified by affinity chromatography
      and subsequently subjected to protease digestion. The SP-C forms were recovered
      from the digestion mixtures by organic extraction and further purified by size
      exclusion chromatography. The two recombinant SP-C variants so obtained retained
      more than 50% alpha-helical content and showed surface activity comparable to the
      native protein, as measured by surface spreading of lipid/protein suspensions and
      from compression pi-A isotherms of lipid/protein films. Compared to the protein
      purified from porcine lungs, the recombinant SP-C forms improved movement of
      phospholipid molecules into the interface (during adsorption), or out from the
      interfacial film (during compression), suggesting new possibilities to develop
      improved therapeutic preparations.

PMID- 16631110
TI  - The relationship between rumination, avoidance and depression in a non-clinical
      sample.
AB  - Recent commentaries have proposed conceptualizations of rumination in terms of
      both cognitive and behavioral avoidance. This study examined the relationship
      between rumination, avoidance and depression using a newly developed self-report
      measure of avoidance in depression, the Cognitive-Behavioral Avoidance Scale
      (CBAS) [Ottenbreit, N.D., & Dobson, K.S. (2004). Avoidance and depression: The
      construction of the cognitive-behavioral avoidance scale. Behaviour Research and
      Therapy, 42, 293-313]. A non-clinical sample (N=104) of undergraduate students
      completed self-report measures of depression, anxiety, rumination and avoidance.
      Rumination, avoidance and depression were all significantly correlated.
      Rumination and behavioral avoidance remained intercorrelated when anxiety was
      controlled, confirming an association that is independent of anxiety. By
      contrast, the relationship between cognitive avoidance and rumination disappeared
      when anxiety was partialled out. Notably, avoidance predicted unique variance in
      depression scores, over and above anxiety and rumination. Consistent with the
      proposal of Ottenbreit and Dobson [Avoidance and depression: The construction of
      the cognitive-behavioral avoidance scale. Behaviour Research and Therapy, 42, 293
      313], our findings support the value of clinicians and psychopathologists giving
      consideration to avoidance in their conceptualization of depression.

PMID- 16631111
TI  - Imaging of single mRNA molecules moving within a living cell nucleus.
AB  - In eukaryotic cells, pre-mRNAs are transcribed in the nucleus, processed by 5'
      capping, 3'-polyadenylation, and splicing, and exported to the cytoplasm for
      translation. To examine the nuclear mRNA transport mechanism, intron-deficient
      mRNAs of truncated beta-globin and EGFP were synthesized, fluorescently labeled
      in vitro, and injected into the nucleus of living Xenopus A6 cells. The
      trajectories of single mRNA molecules in the nucleus were visualized using video
      rate confocal microscopy. Approximately half the mRNAs moved by Brownian motion
      in the nucleoplasm, except the nucleoli, with an apparent diffusion coefficient
      of 0.2microm(2)/s, about 1/150 of that in water. The slow diffusion could not be
      explained by simple diffusion obeying the Stokes-Einstein equation, suggesting
      interactions of the mRNAs with nuclear components. The remaining mRNAs were
      stationary with an average residence time of about 30s, comparable to the time
      required for mRNA diffusion from the site of synthesis to nuclear pores.

PMID- 16631112
TI  - Use of electrospray tandem mass spectrometry for identification of microcystins
      during a cyanobacterial bloom event.
AB  - Drastic environmental conditions such as elevated temperature, abrupt pH
      variation, low turbulence, and high nutrient inputs can enhance the development
      of toxic cyanobacterial blooms in lakes and reservoirs. This study describes the
      occurrence of four microcystin variants (MC) in a bloom in the eutrophic
      reservoir Billings, in Sao Paulo City. The bloom sample was collected in October
      2003, and Microcystis were the main genus found. The MC were separated and
      purified by reverse phase high performance liquid chromatography (RP-HPLC). Their
      structures were elucidated by electrospray ionization tandem mass spectrometry
      (ESI-MS/MS) and four MC variants were determined: MC-RR, MC-LR, MC-YR, and MC
      hRhR. MC-hRhR is described for the first time as a new variant of MC with two
      homoarginines at positions 2 and 4 in its structure. ESI-MS/MS analysis thus
      provides a powerful and convenient tool for the determination of variants of MC.
      These results represent an important contribution to the knowledge of the
      biochemistry of toxic cyanobacteria and their toxins, specifically in Sao Paulo
      State.

PMID- 16631113
TI  - A splice variant of RILP induces lysosomal clustering independent of dynein
      recruitment.
AB  - The small GTPase Rab7 controls fusion and transport of late endocytic
      compartments. A critical mediator is the Rab7 effector RILP that recruits the
      minus-end dynein-dynactin motor complex to these compartments. We identified a
      natural occurring splice variant of RILP (RILPsv) lacking only 27 amino acids
      encoded by exon VII. Both variants bind Rab7, prolong its GTP-bound state, and
      induce clustering of late endocytic compartments. However, RILPsv does not
      recruit the dynein-dynactin complex, implicating exon VII in motor recruitment.
      Clustering might still occur via dimerization, since both RILP and RILPsv are
      able to form hetero- and homo-dimers. Moreover, both effectors compete for Rab7
      binding but with different outcome for dynein-dynactin recruitment and transport.
      Hence, RILPsv provides an extra dimension to the control of vesicle fusion and
      transport by the small GTPase Rab7.

PMID- 16631114
TI  - Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein
      1 in patients with diabetes mellitus.
AB  - Increased monocyte recruitment into subendothelial space in atherosclerotic
      lesions is one of the hallmarks of diabetic angiopathy. The aim of this study was
      to determine the state of peripheral blood monocytes in diabetes associated with
      atherosclerosis. Diabetic patients treated with/without an oral hypoglycemic
      agent and/or insulin for at least 1 year were recruited (n=106). We also included
      24 non-diabetic control subjects. We measured serum levels of monocyte
      chemoattractant protein (MCP)-1, fasting plasma glucose (FPG), HbA1c, total
      cholesterol, triglyceride, body mass index (BMI), high sensitivity CRP (hs-CRP)
      and evaluated CCR2, CD36, CD68 expression on the surface of monocytes. Serum MCP
      1 levels were significantly (p<0.05) higher in diabetic patients than in normal
      subjects. In diabetic patients, serum MCP-1 levels correlated significantly with
      FPG, HbA1c, triglyceride, BMI, and hs-CRP. The expression levels of CCR2, CD36,
      and CD68 on monocytes were significantly increased in diabetic patients and were
      more upregulated by MCP-1 stimulation. Our data suggest that elevated serum MCP-1
      levels and increased monocyte CCR2, CD36, CD68 expression correlate with poor
      blood glucose control and potentially contribute to increased recruitment of
      monocytes to the vessel wall in diabetes mellitus.

PMID- 16631115
TI  - Impaired coactivator activity of the Gly482 variant of peroxisome proliferator
      activated receptor gamma coactivator-1alpha (PGC-1alpha) on mitochondrial
      transcription factor A (Tfam) promoter.
AB  - Mitochondrial dysfunction may cause diabetes or insulin resistance. Peroxisome
      proliferation-activated receptor-gamma (PPAR-gamma) coactivator-1 alpha (PGC
      1alpha) increases mitochondrial transcription factor A (Tfam) resulting in
      mitochondrial DNA content increase. An association between a single nucleotide
      polymorphism (SNP), G1444A(Gly482Ser), of PGC-1alpha coding region and insulin
      resistance has been reported in some ethnic groups. In this study, we
      investigated whether a change of glycine to serine at codon 482 of PGC-1alpha
      affected the Tfam promoter activity. The cDNA of PGC-1alpha variant bearing
      either glycine or serine at 482 codon was transfected into Chang human hepatocyte
      cells. The PGC-1alpha protein bearing glycine had impaired coactivator activity
      on Tfam promoter-mediated luciferase. We analyzed the PGC-1alpha genotype G1444A
      and mitochondrial DNA (mtDNA) copy number from 229 Korean leukocyte genomic DNAs.
      Subjects with Gly/Gly had a 20% lower amount of peripheral blood mtDNA than did
      subjects with Gly/Ser and Ser/Ser (p<0.05). No correlation was observed between
      diabetic parameters and PGC-1alpha genotypes in Koreans. These results suggest
      that PGC-1alpha variants with Gly/Gly at 482nd amino acid may impair the Tfam
      transcription, a regulatory function of mitochondrial biogenesis, resulting in
      dysfunctional mtDNA replication.

PMID- 16631116
TI  - Fibronectin is essential for hepatitis B virus propagation in vitro: may be a
      potential cellular target?
AB  - Previous studies in our laboratory strongly suggested that fibronectin was
      upregulated by hepatitis B virus (HBV) in HepG2.2.15 cells. Report by Budkowska A
      also indicated that human liver fibronectin could bind HBV in a species
      restricted manner. Therefore, it is reasonable to ask whether inhibiting
      fibronectin expression might have anti-HBV activity and whether fibronectin might
      be developed as a new potential cellular target for anti-HBV drugs. By using
      fibronectin antisense oligonucleotide (ASODN), fibronectin antibody, and
      Protocatechuic aldehyde (PA), we were able to show that HBV productions in
      HepG2.2.15 cell culture were reduced in a dose-dependent manner by fibronectin
      inhibition. In addition, we found that treatment with ASODNs, fibronectin
      antibody, and PA did not affect HepG2.2.15 cell viability. Furthermore, we
      observed that fibronectin inhibition sensitized HBV to anti-HBV drugs. In
      summary, this study demonstrates that fibronectin is essential for HBV
      propagation and also provides some evidences for the potential of fibronectin as
      a new cellular target for HBV infection therapy.

PMID- 16631117
TI  - Ubc9 interacts with SOX4 and represses its transcriptional activity.
AB  - SOX4 is a member of SOX transcriptional factor family that is crucial for many
      cellular processes. In this study, a yeast two-hybrid screening of human mammary
      cDNA library identified human ubiquitin-conjugating enzyme 9 (hUbc9) that
      interacted with SOX4. This interaction was confirmed by GST pull-down in vitro
      and co-immunoprecipitation assays in vivo. Deletion mapping demonstrated that HMG
      box domain of SOX4 is required to mediate the interaction with Ubc9 in yeast.
      Furthermore, confocal microscopy showed that Ubc9 co-localized with SOX4 in the
      nucleus. Luciferase assays found that Ubc9 specifically repressed SOX4
      transcriptional activity in 293T cells. We further demonstrated that Ubc9 could
      functionally repress the transcriptional activity of endogenous SOX4 induced by
      progesterone in T47D cells. The C93S mutant of Ubc9, which abrogates SUMO-1
      conjugation activity, did not abolish the ability to repress SOX4 activity. It
      shows that Ubc9 interacts with SOX4 and represses its transcriptional activity
      independent of its SUMO-1-conjugating activity.

PMID- 16631118
TI  - Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for
      antiviral activity.
AB  - Oligonucleotide agents (ODN) are emerging as attractive alternatives to chemical
      drugs. However, the clinical use of ODNs as therapeutics has been hindered by
      their susceptibility to degradation by cellular enzymes and their limited ability
      to penetrate intact cells. We have used various liposome-mediated transfection
      agents, for the in vitro delivery of DNA thioaptamers into U373-MAGI-CCR5 cells.
      Our lead thioaptamer, R12-2, targets the RNase H domain of the HIV-1 reverse
      transcriptase (RT) and inhibits viral infection in U373-MAGI-CCR5 cells. R12-2, a
      62-base-pair, double-stranded DNA molecule with a monothio-phosphate modified
      backbone, was selected through a novel combinatorial selection method. We studied
      the use of oligofectamine (OF), TFX-20, Transmessenger (TM), and Gene Jammer (GJ)
      for transfection of the thio-modified DNA aptamers. OF-transfected U373-MAGI-CCR5
      cells resulted in 68% inhibition of HIV infection in the treated cells compared
      to the untreated control. Inhibition was observed in a dose-dependent manner with
      maximal inhibition of 83%. In this report, we demonstrate that monothioate
      modified DNA duplex oligonucleotides can be efficiently delivered into cells by
      liposome-based transfection agents to inhibit HIV replication.

PMID- 16631119
TI  - TNFR-Fc fusion protein expressed by in vivo electroporation improves survival
      rates and myocardial injury in coxsackievirus induced murine myocarditis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of the major cytokines that
      modulate the immune response in viral myocarditis, but its role has not yet been
      thoroughly evaluated. We antagonized TNF-alpha using the expressed soluble p75
      TNF receptor linked to the Fc portion of the human IgG1 gene (sTNFR:Fc) by in
      vivo electroporation, and evaluated its effects on experimental coxsackieviral B3
      (CVB3) myocarditis. A plasmid DNA encoding sTNFR:Fc (15microg/mouse) was injected
      into the gastrocnemius muscles of Balb/C male mice followed by electroporation
      (day -1). Control mice were injected with an empty vector. One day after
      electroporation, mice were infected with CVB3 (day 0). Serum levels of sTNFR:Fc
      increased from day 2 and peaked at day 5 following electroporation. The heart
      virus titers of sTNFR:Fc mice were higher than those of controls at day 3.
      However, subsequent to day 12, the survival rates of the sTNFR:Fc mice were
      significantly higher than those of the controls (36% versus 0% at day 27,
      P<0.01). Histopathological examination indicated that inflammation and myocardial
      fibrosis were significantly decreased in sTNFR:Fc mice at day 12. The expressed
      sTNFR:Fc could modulate the inflammatory process during the post-viremic phase of
      viral myocarditis.

PMID- 16631120
TI  - Promoter analysis of interleukin 19.
AB  - Interleukin (IL)-19 belongs to the IL-10 family which includes IL-19, IL-20, IL
      22, AK155, and MDA-7. IL-10 is a potent immunomodulatory cytokine with
      implications for pathogenesis in various autoimmune diseases. Polymorphism of the
      IL-10 promoter region correlates with disease outcome. To understand the gene
      regulation of IL-19, we analyzed the IL-19 promoter region. A regulatory region
      (PE), 148bp upstream of exon 1 of IL-19 and linked to a luciferase reporter gene,
      supported luciferase activity 13 times greater than that supported by a negative
      promoterless control. An electrophoretic mobility shift assay (EMSA) showed
      specific binding sites for the transcription factors of the oligonucleotides PE1
      (-148 to -98) derived from PE. We identified the sequence TGTGGT (-142 to -138)
      on PE1 as the binding site for the transcription factor AML1, and crucial for the
      promoter activity of IL-19 because substituting 1bp in the PE region (-139G-->T)
      abolished IL-19 promoter activity.

PMID- 16631121
TI  - Glycine receptor activation regulates short-term plasticity in CA1 area of
      hippocampal slices of rats.
AB  - Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their
      roles in synaptic transmission are unclear. In this study, we examined the effect
      of GlyR activation on paired-pulse stimulation of the whole-cell postsynaptic
      currents (PSCs) in the Schaffer-CA1 synapses in rat hippocampal slices. Bath
      application of glycine reduced the amplitude of PSCs, accompanied by an increase
      in holding current and resting conductance. Moreover, glycine application
      increased the paired-pulse ratio (PPR) of PSCs significantly, an effect largely
      abolished by the GlyR specific antagonist strychnine. Interestingly, glycine
      application had no significant effect on either the amplitude or the PPR of
      excitatory postsynaptic currents (EPSCs). Our findings suggest that GlyR
      activation regulates hippocampal short-term plasticity by altering GABAergic
      neurotransmission.

PMID- 16631122
TI  - Cochlear alterations in deaf and unaffected subjects carrying the deafness
      associated A1555G mutation in the mitochondrial 12S rRNA gene.
AB  - The A1555G mutation in the mitochondrial small ribosomal RNA gene (12S rRNA) has
      been associated with aminoglycoside-induced, nonsyndromic hearing loss. However,
      the clinical phenotype of A1555G carriers is extremely variable. In the present
      study, we have performed an audiological evaluation of a group of deaf patients
      and hearing carriers of mutation A1555G with the aim to assess the prevalence of
      the mutation and determine the associated cochlear alterations. Fifty-four
      patients affected of nonsyndromic hearing loss were screened for the presence of
      the A1555G mitochondrial mutation. Nine of the familial cases (21%) carried the
      A1555G mutation, whereas the mutation was not found in any of the sporadic cases.
      The positive cases and some of their family members underwent a clinical study
      consisting in a clinical evaluation and audiological testing. The phenotype of
      A1555G patients varied in age of onset and severity of hearing loss, ranging from
      profound deafness to completely normal hearing. The audiometric alterations
      showed bilateral hearing loss, being more severe at high frequencies. Otoacoustic
      emissions were absent in deaf A1555G carriers, and auditory brainstem response
      indicated a prolonged Wave I, suggesting a cochlear dysfunction without any
      effect of the auditory nerve. Moreover, all hearing carriers of A1555G also
      presented alterations in cochlear physiology. In conclusion, the A1555G
      mitochondrial mutation causes a cochlear form of deafness, characterized by a
      more severe loss of hearing at high frequencies. Although the expression of the
      mutation is variable, cochlear alterations are present in all carriers of
      mutation A1555G.

PMID- 16631123
TI  - Expression analysis and prognostic significance of the SRA1 gene, in ovarian
      cancer.
AB  - The SR-related-CTD-associated-factors (SCAFs) have the ability to interact with
      the C-terminal domain of the RNA polymerase II, linking this way transcription to
      splicing. SRA1 (SR-A1) gene, encoding for a human high-molecular weight SCAF
      protein, is located on chromosome 19, between the IRF3 and the R-RAS oncogene and
      it has been demonstrated from members of our group that SRA1 is constitutively
      expressed in most of the human tissues, while it is overexpressed in a subset of
      ovarian tumors. In this study, we examine the expression of SRA1 gene in 111
      ovarian malignant tissues and in the human ovarian carcinoma cell lines OVCAR-3,
      TOV21-G, and ES-2, using a semi-quantitative RT-PCR method. SRA1 gene was
      overexpressed in 61/111 (55%) of ovarian carcinomas. This higher expression was
      positively associated to the size of the tumor (p<0.001), the grade and the stage
      of the disease (p=0.003 and p=0.006, respectively), and the debulking success
      (p<0.001). Kaplan-Meier survival analysis revealed that lower SRA1 expression
      increases the probability of both the longer overall and the progression free
      survival of the patients. Multivariate Cox regression analysis revealed that SRA1
      may be used as an independent prognostic biomarker in ovarian cancer. Our results
      suggest that SRA1 is associated with cancer progression and may possibly be
      characterized as a new marker of unfavorable prognosis for ovarian cancer.

PMID- 16631124
TI  - Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5
      hydroxytryptamine uptake and on monoamine oxidase activity.
AB  - This study investigated for the first time the potential effects of cis- and
      trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5
      hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by
      human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and
      t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA
      and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human
      platelets. In both experimental models, t-RESV was slightly more efficient than c
      RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less
      selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30
      microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration
      dependently inhibited the enzymatic activity of commercial (human recombinant)
      MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than
      t-RESV. In addition, both RESV isomers were slight but significantly more
      selective against MAO-A than against MAO-B. Since the principal groups of drugs
      used in the treatment of depressive disorders are NA/5-HT uptake or MAO
      inhibitors, under the assumption that the RESV isomers exhibit a similar
      behaviour in humans in vivo, our results suggest that these natural polyphenols
      may be of value as structural templates for the design and development of new
      antidepressant drugs with two important biochemical activities combined in the
      same chemical structure: NA/5-HT uptake and MAO inhibitory activity.

PMID- 16631125
TI  - Activation of phosphoinositide 3-kinase and Src family kinase is required for
      respiratory burst in rat neutrophils stimulated with artocarpol A.
AB  - Artocarpol A (ART), a natural product isolated from Artocarpus rigida, stimulated
      superoxide anion (O2*-) generation, which was inhibited by 2-(4-morpholinyl)-8
      phenyl-4H-1-benzopyran-4-one (LY 294002), a phosphoinositide 3-kinase (PI3K)
      inhibitor, in rat neutrophils. ART stimulated phosphorylation of protein kinase B
      (PKB/Akt) on both T308 and S473 residues, and LY 294002 inhibited these effects.
      Rat neutrophils expressed both class IA PI3K subunits (p85, p110alpha, p110beta,
      and p110delta) and a class IB PI3K subunit (p110gamma) as assessed by a
      combination of Western blotting and reverse transcription-polymerase chain
      reaction (RT-PCR) approaches. Stimulation of neutrophils with ART evoked
      phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) formation, which
      reached a maximal level at 2 min and was attenuated by LY 294002, as evidenced by
      immunofluorescence microscopy and by flow cytometry. Detectable membrane
      association of class IA PI3Ks, class IB PI3K and Ras was seen as early as 1.5,
      0.5 and 1.5 min, respectively, after stimulation with ART. The kinetics of ART
      induced Ras activation paralleled the kinetics of class IA PI3Ks recruitment to
      membrane caused by ART, and the p85 and p110gamma immunoprecipitates contain Ras.
      ART stimulated Src family kinase activation, which was detectable within 1.5 min
      of incubation with ART. Both Src kinase activity and PtdIns(3,4,5)P3 formation in
      ART-stimulated neutrophils were inhibited by 4-amino-1-tert-butyl-3-(1'
      naphthyl)pyrazolo[3,4-d]pyrimidine (PP1 analog). PP1 analog also attenuated the
      ART-stimulated O2*- generation in rat neutrophils. These results indicate that
      the stimulation of respiratory burst by ART in neutrophils implicates PI3K
      signaling.

PMID- 16631126
TI  - A neurotrophic model for stress-related mood disorders.
AB  - There is a growing body of evidence demonstrating that stress decreases the
      expression of brain-derived neurotrophic factor (BDNF) in limbic structures that
      control mood and that antidepressant treatment reverses or blocks the effects of
      stress. Decreased levels of BDNF, as well as other neurotrophic factors, could
      contribute to the atrophy of certain limbic structures, including the hippocampus
      and prefrontal cortex that has been observed in depressed subjects. Conversely,
      the neurotrophic actions of antidepressants could reverse neuronal atrophy and
      cell loss and thereby contribute to the therapeutic actions of these treatments.
      This review provides a critical examination of the neurotrophic hypothesis of
      depression that has evolved from this work, including analysis of preclinical
      cellular (adult neurogenesis) and behavioral models of depression and
      antidepressant actions, as well as clinical neuroimaging and postmortem studies.
      Although there are some limitations, the results of these studies are consistent
      with the hypothesis that decreased expression of BDNF and possibly other growth
      factors contributes to depression and that upregulation of BDNF plays a role in
      the actions of antidepressant treatment.

PMID- 16631127
TI  - The benzodiazepine alprazolam dissociates contextual fear from cued fear in
      humans as assessed by fear-potentiated startle.
AB  - BACKGROUND: The startle reflex is potentiated by aversive states. It has been
      proposed that phasic startle potentiation to a threat cue and sustained startle
      potentiation to contextual stimuli reflect distinct processes mediated by
      different brain structures. The present study tested the hypothesis that
      alprazolam would reduce the sustained startle potentiation to contextual threats
      but not the startle potentiation to a threat cue. METHODS: Sixteen healthy
      subjects received each of four treatments: placebo, .5 mg of alprazolam, 1 mg of
      alprazolam, and 50 mg of diphenhydramine (Benadryl) 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 shocks were
      administered unpredictably, and a third condition in which no shocks were
      anticipated. Acoustic startle were delivered regularly across conditions.
      RESULTS: Phasic startle potentiation to the threat cue in the predictable
      condition was not affected by alprazolam. In contrast, the sustained increase in
      startle in the predictable and unpredictable conditions was reduced significantly
      by the high dose of alprazolam. CONCLUSIONS: Startle responses to an explicit
      threat cue and to an aversive context are psychopharmacologically distinct,
      suggesting that they may represent functionally dissociable aversive states.

PMID- 16631128
TI  - Acute stress and nicotine cues interact to unveil locomotor arousal and activity
      dependent gene expression in the prefrontal cortex.
AB  - BACKGROUND: This study examines the interactive effects of acute stress and
      nicotine-associated contextual cues on locomotor activity and activity-dependent
      gene expression in subregions of the prefrontal cortex. METHODS: Locomotor
      activity of rats was measured in a context associated with either low-dose
      nicotine or saline administration with or without 5 minutes of pre-exposure to
      ferrets, a nonphysical stressor. After 45 minutes in the test environment, plasma
      corticosterone levels and mRNA levels of the immediate-early genes Arc, NGFI-B,
      and c-Fos in prefrontal and primary motor cortical subregions were measured.
      RESULTS: Stress alone increased plasma corticosterone and prefrontal cortex gene
      expression. Low-dose nicotine cues had no effect on corticosterone levels nor did
      they elicit conditioned motor activation, and they caused minor elevations in
      gene expression. Stress and low-dose nicotine cues, however, interacted to elicit
      conditioned motor activation and further increases in early response gene
      expression in prefrontal but not in the primary motor cortical subregions.
      CONCLUSIONS: Stress interacts with nicotine-associated cues to uncover locomotor
      arousal, a state associated with prefrontal neuronal activation and immediate
      early gene expression. Thus, in nicotine-experienced individuals, stress may be
      an important determinant of subjective reactivity and prefrontal cortex
      activation that occurs in response to nicotine-associated cues.

PMID- 16631129
TI  - Evaluation of a susceptibility gene for schizophrenia: genotype based meta
      analysis of RGS4 polymorphisms from thirteen independent samples.
AB  - BACKGROUND: Associations between schizophrenia (SCZ) and polymorphisms at the
      regulator of G-protein signaling 4 (RGS4) gene have been reported (single
      nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ
      candidate genes, studies have been inconsistent with respect to the associated
      alleles. METHODS: In an effort to resolve the role for RGS4 in SCZ
      susceptibility, we undertook a genotype-based meta-analysis using both published
      and unpublished family-based and case-control samples (total n = 13,807).
      RESULTS: The family-based dataset consisted of 10 samples (2160 families).
      Significant associations with individual SNPs/haplotypes were not observed. In
      contrast, global analysis revealed significant transmission distortion (p =
      .0009). Specifically, analyses suggested overtransmission of two common
      haplotypes that account for the vast majority of all haplotypes. Separate
      analyses of 3486 cases and 3755 control samples (eight samples) detected a
      significant association with SNP 4 (p = .01). Individual haplotype analyses were
      not significant, but evaluation of test statistics from individual samples
      suggested significant associations. CONCLUSIONS: Our collaborative meta-analysis
      represents one of the largest SCZ association studies to date. No individual risk
      factor arose from our analyses, but interpretation of these results is not
      straightforward. Our analyses suggest risk due to at least two common haplotypes
      in the presence of heterogeneity. Similar analysis for other putative
      susceptibility genes is warranted.

PMID- 16631130
TI  - Functional correlates of verbal memory deficits emerging during nicotine
      withdrawal in abstinent adolescent cannabis users.
AB  - BACKGROUND: Cannabis remains the most widely used illicit substance by
      adolescents and is typically consumed by this population in the context of
      ongoing tobacco use. Human studies have shown that both cannabis and tobacco
      exert effects on cognitive function; however, little is known about possible
      interacting effects of these drugs on brain function and cognition during
      adolescent development. METHODS: Verbal learning and memory were assessed in 20
      adolescent users of tobacco and cannabis and 25 adolescent tobacco users with
      minimal history of cannabis use. Functional magnetic resonance imaging was used
      to examine brain function and functional connectivity while a subset of these
      subjects performed a verbal working memory task. RESULTS: Delayed recall of
      verbal stimuli deteriorated during nicotine withdrawal among cannabis users but
      not among comparison subjects. During high verbal working memory load, nicotine
      withdrawal selectively increased task-related activation of posterior cortical
      regions and was associated with disruption of frontoparietal connectivity in
      adolescent cannabis users relative to comparison subjects. CONCLUSIONS: These
      observations suggest that cannabis use during adolescent development may disrupt
      neurocircuitry supporting verbal memory formation and that deficits associated
      with disruption of these neurocircuits are unmasked during nicotine withdrawal.

PMID- 16631131
TI  - The fibroblast growth factor system and mood disorders.
AB  - Recent evidence now suggests the involvement of the fibroblast growth factor
      (FGF) system in mood disorders. Specifically, several members of the FGF family
      have been shown to be dysregulated in individuals with major depression. In this
      review, we will introduce the FGF system in terms of structure and function
      during development, in adulthood, and in various regions and cell types. We will
      also review the FGF system as a mediator of neural plasticity. Furthermore, this
      review will summarize animal as well as human studies. The majority of animal
      studies have focused on stress, environmental enrichment, pharmacological
      manipulations, and the hippocampus. By contrast, human studies have focused on
      volumetric measurements, antidepressant literature, and, most recently, post
      mortem microarray experiments. In summary, a reduced tone in the FGF system might
      alter brain development or remodeling and result in a predisposition or
      vulnerability to mood disorders, including major depression.

PMID- 16631132
TI  - Fluoxetine modulates the circadian biological clock via phase advances of
      suprachiasmatic nucleus neuronal firing.
AB  - BACKGROUND: The documented ability of serotonin (5-HT) to directly modulate
      circadian rhythms prompted interest in a similar role for therapeutic agents that
      readily enhance 5-HT neurotransmission, namely the selective serotonin reuptake
      inhibitors (SSRIs). METHODS: Extracellular recordings of unit firing of
      suprachiasmatic nucleus (SCN) neurons maintained in slice culture enabled
      determinations of circadian rhythmicity. Shifts in the peak of activity were
      determined during the next circadian cycle following drug exposure. RESULTS:
      Fluoxetine (10 microm, 60 minutes incubation) produced robust phase advances only
      in the presence of L-tryptophan (.5 microm), added to maintain serotonergic tone.
      CONCLUSIONS: Actions of SSRIs at the level of the circadian biological clock add
      to the list of pharmacological effects for this drug class and encourage
      speculation as to their importance clinically.

PMID- 16631133
TI  - Genetic mouse models of schizophrenia: from hypothesis-based to susceptibility
      gene-based models.
AB  - Translation of human genetic mutations into genetic mouse models is an important
      strategy to study the pathogenesis of schizophrenia, identify potential drug
      targets, and test new drugs for new antipsychotic treatments. Although it is
      impossible to recapitulate the full spectrum of schizophrenia symptoms in animal
      models, hypothesis-driven genetic mouse models have been successful in
      reproducing several schizophrenia-like behaviors and uncovering the roles of
      specific genes in dopamine and glutamine neurotransmission systems in mediating
      schizophrenia-like behaviors. Recent discoveries of susceptibility genes for
      schizophrenia and recognition of cognitive dysfunction as a core feature of
      schizophrenia and a phenotype of susceptibility for schizophrenia offer
      opportunities to develop newer genetic mouse models based on susceptibility. This
      new generation of genetic mouse models could shed light on the etiology of
      schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more
      effective therapy.

PMID- 16631134
TI  - Contributions of mouse models to understanding of age- and noise-related hearing
      loss.
AB  - Once an oddity, mice have become the most widely used hearing research model.
      Their value for research in noise-induced hearing loss (NIHL) stems from their
      high vulnerability to noise and reduced variance of results, made possible by
      genetic standardization. To research in age-related hearing loss (ARHL), they
      offer economies of small size and a short lifespan, both of which reduce housing
      costs. Inbred mouse strains show a wide range of noise sensitivities and rates of
      hearing loss with age. These can be studied using classical genetic analysis, as
      well as hypothesis-driven experiments utilizing genetic engineering. Through such
      investigations, presently 3 loci have been identified to date that contribute to
      NIHL, 10 that promote ARHL, and at least 6 loci that promote both. The types of
      genes involved implicate homeostatic and protective mechanisms as key to the
      appearance of either type of pathology and support a causal link between injury
      and some apparent ARHL. While the majority of mouse ARHL models examined most
      closely resemble sensory ARHL, recent work has identified mice possessing the
      essential characteristics of neural and strial ARHL. Using these models, it
      should be possible to identify genes and alleles that promote the major forms of
      ARHL and their combinations.

PMID- 16631135
TI  - The hypothalamo-pituitary axis responses to lipopolysaccharide-induced
      endotoxemia in mice lacking inducible nitric oxide synthase.
AB  - Nitric oxide (NO) generated by inducible NO synthase (iNOS) may be implicated in
      the biological responses of the central nervous system to immune stimuli. To
      elucidate the role of iNOS in the hypothalamo-pituitary axis in responses to
      endotoxemia, using iNOS knockout (KO) mice, we examined the levels of c-fos, a
      neural activational marker, and corticotropin-releasing hormone (CRH) gene
      transcription in the paraventricular nucleus (PVN) and central amygdala (CeAMY)
      during lipopolysaccharide (LPS)-induced endotoxemia. In addition, the serum
      adrenocorticotropic hormone (ACTH) levels were also examined during endotoxemia.
      Following the intraperitoneal administration of LPS (1 mg/kg), the levels of the
      c-fos gene expression significantly increased in the PVN and the CeAMY regardless
      of the genotype. However, the disruption of the iNOS gene resulted in a
      significant decrease in the c-fos gene induction in the PVN in comparison to that
      observed in control mice. LPS administration caused a significant increase in CRH
      mRNA levels in the PVN and CeAMY regardless of genotype. However, the LPS-induced
      upregulation of CRH mRNA was significantly attenuated in the PVN of iNOS KO mice
      in comparison to that in the control mice. In contrast, no such genotype
      differences in the neural activity or CRH gene transcription were observed in the
      CeAMY. The serum ACTH responses to LPS were also significantly blunted in the
      iNOS KO mice in comparison to the control mice. These results suggest that iNOS
      derived NO may therefore play a stimulatory role in the activity of the
      hypothalamo-pituitary axis during endotoxemia.

PMID- 16631136
TI  - Chronic ferritin expression within murine dopaminergic midbrain neurons results
      in a progressive age-related neurodegeneration.
AB  - Ferritin elevation has been reported by some laboratories to occur within the
      substantia nigra (SN), the area of the brain affected in Parkinson's disease
      (PD), but whether such an increase could be causatively involved in
      neurodegeneration associated with the disorder is unknown. Here, we report that
      chronic ferritin elevation in midbrain dopamine-containing neurons results in a
      progressive age-related neurodegeneration of these cells. This provides strong
      evidence that chronic ferritin overload could be directly involved in age-related
      neurodegeneration such as occurs in Parkinson's and other related diseases.

PMID- 16631137
TI  - Spatial extent of CBF response during whisker stimulation using trial averaged
      laser Doppler imaging.
AB  - The spatial pattern of activation in response to multiple whisker stimulation was
      studied using high-resolution laser Doppler (LD) imaging in urethane-anesthetized
      rats. LD flux change representing cerebral blood flow (CBF) responses were
      analyzed from a single trial or after averaging a number of similar trials. CBF
      change in a single trial was observed predominantly over pixels having low
      baseline flux values (microvessels), which included diffuse circular patterns of
      activation 400-800 microm in diameter similar to the histological dimensions of
      individual barrels established in the layer IV of the rat somatosensory cortex.
      The overall activation pattern varied considerably between each trial (only about
      9-10% overlap); however, the diffuse circular pattern of activation was
      reproducible in every single trial within and across all rats. With trial
      averaging, no significant increase was observed in the outer boundary of
      activation, but the number of activated pixels increased within the diffuse
      circular patterns of activation. Emergence of further active pixels primarily
      within the diffuse circular regions of activity with trial averaging indicates
      distinct CBF responses in the septal and barrel regions, with a lesser LD signal
      to noise ratio in the barrel core.

PMID- 16631138
TI  - Ghrelin-induced sleep responses in ad libitum fed and food-restricted rats.
AB  - Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and
      a well-characterized food intake regulatory peptide. Hypothalamic ghrelin-,
      neuropeptide Y (NPY)-, and orexin-containing neurons form a feeding regulatory
      circuit. Orexins and NPY are also implicated in sleep-wake regulation. Sleep
      responses and motor activity after central administration of 0.2, 1, or 5 microg
      ghrelin in free-feeding rats as well as in feeding-restricted rats (1 microg
      dose) were determined. Food and water intake and behavioral responses after the
      light onset injection of saline or 1 microg ghrelin were also recorded. Light
      onset injection of ghrelin suppressed non-rapid-eye-movement sleep (NREMS) and
      rapid-eye-movement sleep (REMS) for 2 h. In the first hour, ghrelin induced
      increases in behavioral activity including feeding, exploring, and grooming and
      stimulated food and water intake. Ghrelin administration at dark onset also
      elicited NREMS and REMS suppression in hours 1 and 2, but the effect was not as
      marked as that, which occurred in the light period. In hours 3-12, a secondary
      NREMS increase was observed after some doses of ghrelin. In the feeding
      restricted rats, ghrelin suppressed NREMS in hours 1 and 2 and REMS in hours 3
      12. Data are consistent with the notion that ghrelin has a role in the
      integration of feeding, metabolism, and sleep regulation.

PMID- 16631139
TI  - Limb ischemic preconditioning induces brain ischemic tolerance via p38 MAPK.
AB  - It has been reported that limb ischemic preconditioning (LIP) could induce brain
      ischemic tolerance. In the present study, we investigated the role of p38 MAPK in
      the induction of brain ischemic tolerance by observing expression of
      phosphorylated p38 (p-p38) MAPK in the hippocampus after LIP and the effect of
      p38 MAPK inhibitor SB 203580 on the protection of LIP against delayed neuronal
      death (DND) in the CA1 hippocampus induced normally by brain ischemic insult. The
      results of Flow cytometry and Western blotting showed that expression of p-p38
      MAPK initially increased at 6 h after LIP compared with sham group in the CA1
      hippocampus. The increases reached peak at 12 h and lasted to 24 h after LIP.
      Expression of p-p38 MAPK was also increased in the CA3/dentate gyrus (DG) regions
      after LIP, but the beginning and peaking times were 1 and 3 days after LIP, which
      were relatively later than those in the CA1. Histological evaluation showed that
      LIP protected the CA1 hippocampal pyramidal neurons against DND induced by global
      brain ischemic insult for 8 min, suggesting the occurrence of brain ischemic
      tolerance. Pretreatment with SB 203580 at 30 min before LIP effectively blocked
      the ischemic tolerance induced by LIP. Together, it could be concluded that
      activation of p38 MAPK played an important role in the brain ischemic tolerance
      induced by LIP, and that components of the p38 MAPK cascade might be targets to
      modify neuronal survival in ischemic tolerance.

PMID- 16631140
TI  - Rab3A deletion selectively reduces spontaneous neurotransmitter release at the
      mouse neuromuscular synapse.
AB  - Rab3A is a synaptic vesicle-associated GTP-binding protein thought to be involved
      in modulation of presynaptic transmitter release through regulation of vesicle
      trafficking and membrane fusion. Electrophysiological studies at central nervous
      system synapses of Rab3A null-mutant mice have indicated that nerve stimulation
      evoked transmitter release and its short- and long-term modulation are partly
      dependent on Rab3A, whereas spontaneous uniquantal release is completely
      independent of it. Here, we studied the acetylcholine (ACh) release at the
      neuromuscular junction (NMJ) of diaphragm and soleus muscles from Rab3A-deficient
      mice with intracellular microelectrode methods. Surprisingly, we found 20-40%
      reduction of spontaneous ACh release but completely intact nerve action potential
      evoked release at both high- and low-rate stimulation and during recovery from
      intense release. The ACh release induced by hypertonic medium was also unchanged,
      indicating that the pool of vesicles for immediate release is unaltered at the
      Rab3A-deficient NMJ. These results indicate a selective role of Rab3A in
      spontaneous transmitter release at the NMJ which cannot or only partly be taken
      over by the closely related Rab3B, Rab3C, or Rab3D isoforms when Rab3A is
      deleted. It has been hypothesized that Rab3A mutation underlies human presynaptic
      myasthenic syndromes, in which severely reduced nerve action potential-evoked ACh
      release at the NMJ causes paralysis. Our observation that Rab3A deletion does not
      reduce evoked ACh release at any stimulation rate at the mouse NMJ, argues
      against this hypothesis.

PMID- 16631141
TI  - Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the
      brain, and their regulation by diet and cold stress.
AB  - Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and
      released from secretory vesicles and are expressed widely in nervous, endocrine,
      and neuroendocrine tissues, play roles in the regulation of body weight, feeding,
      and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments,
      several of which are biologically active. We utilized a highly sensitive and
      specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides,
      developed another against immunoreactive, VGF-derived AQEE30 peptides, and
      quantified these peptides in various mouse tissues and brain regions.
      Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were
      highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels
      were highest in the pancreas and spinal cord, and in brain, PEN was most abundant
      in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were
      expressed in hypothalamus, a region of the brain that controls feeding and energy
      expenditure, double label immunofluorescence studies were employed. These
      demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS
      peptides, and that the intracellular distributions of these peptides in arcuate
      neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN
      peptide levels in female but not male hypothalamus, while a high fat diet
      increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF
      and SAAS-derived peptides are therefore widely expressed in endocrine,
      neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are
      differentially regulated in the brain by diet and cold stress.

PMID- 16631142
TI  - Chronic ethanol drinking reduces native T-type calcium current in the thalamus of
      nonhuman primates.
AB  - BACKGROUND: Chronic ethanol use is known to disrupt normal sleep rhythms, but the
      cellular basis for this disruption is unknown. An important contributor to normal
      sleep patterns is a low-threshold calcium current mediated by T-type calcium
      channels. The T-type calcium current underlies burst responses in thalamic nuclei
      that are important to spindle propagation, and we recently observed that this
      current is sensitive to acute low doses of ethanol. METHODS: We used a
      combination of current clamp and voltage clamp recordings in an in vitro brain
      slice preparation of the dorsal lateral geniculate nucleus (LGN) of macaque
      monkeys that have chronically self-administered ethanol to determine whether
      chronic ethanol exposure may affect T-type currents. RESULTS: Current clamp
      recordings from the LGN of ethanol naive macaques showed characteristic burst
      responses. However, recordings from the LGN in macaques that self-administered
      ethanol revealed a significant attenuation of bursts across a range of voltages
      (n=5). Voltage clamp recordings from control LGN neurons (n=16) and neurons
      (n=29) from brain slices from chronically drinking macaques showed no significant
      differences (P>0.05) in T-type current kinetics or in the membrane resistance of
      the thalamic cells between the two cohorts. However, mean T-type current
      amplitude measured in the chronically drinking animals was reduced by 31%
      (P<0.01). CONCLUSIONS: We conclude that chronic ethanol self-administration
      reduces calcium currents in thalamic relay cells without altering underlying
      current kinetics, which may provide a mechanistic framework for the well
      documented disruptions in sleep/wake behavior in subjects with chronic ethanol
      exposure.

PMID- 16631143
TI  - Synaptic proteins and phospholipids are increased in gerbil brain by
      administering uridine plus docosahexaenoic acid orally.
AB  - The synthesis of brain phosphatidylcholine may utilize three circulating
      precursors: choline; a pyrimidine (e.g., uridine, converted via UTP to brain
      CTP); and a PUFA (e.g., docosahexaenoic acid); phosphatidylethanolamine may
      utilize two of these, a pyrimidine and a PUFA. We observe that consuming these
      precursors can substantially increase membrane phosphatide and synaptic protein
      levels in gerbil brains. (Pyrimidine metabolism in gerbils, but not rats,
      resembles that in humans.) Animals received, daily for 4 weeks, a diet containing
      choline chloride and UMP (a uridine source) and/or DHA by gavage. Brain
      phosphatidylcholine rose by 13-22% with uridine and choline alone, or DHA alone,
      or by 45% with the combination, phosphatidylethanolamine and the other
      phosphatides increasing by 39-74%. Smaller elevations occurred after 1-3 weeks.
      The combination also increased the vesicular protein Synapsin-1 by 41%, the
      postsynaptic protein PSD-95 by 38% and the neurite neurofibrillar proteins NF-70
      and NF-M by up to 102% and 48%, respectively. However, it had no effect on the
      cytoskeletal protein beta-tubulin. Hence, the quantity of synaptic membrane
      probably increased. The precursors act by enhancing the substrate saturation of
      enzymes that initiate their incorporation into phosphatidylcholine and
      phosphatidylethanolamine and by UTP-mediated activation of P2Y receptors.
      Alzheimer's disease brains contain fewer and smaller synapses and reduced levels
      of synaptic proteins, membrane phosphatides, choline and DHA. The three
      phosphatide precursors might thus be useful in treating this disease.

PMID- 16631144
TI  - The control of attention and actions: current research and future developments.
AB  - In this introductory article of the special issue of Brain Research, we first
      present an overview of some general questions relating to cognitive control. For
      instance, one of the questions that remain to be answered is what control
      mechanisms and their neural underpinnings really 'do', beyond what is done by
      more basic 'computational' or data processing systems in the brain. We then
      briefly describe the four major issues addressed in the separate articles of this
      issue, namely attentional orienting, task set switching, performance and error
      monitoring, and response inhibition. In conclusion, we focus on some new
      methodological directions and illustrate how the study of cognitive control may
      be augmented by relatively newly emerging theoretical and empirical perspectives.

PMID- 16631145
TI  - cis-Regulatory sequences of the genes involved in apoptosis, cell growth, and
      proliferation may provide a target for some of the effects of acute ethanol
      exposure.
AB  - The physiological effects of alcohol are known to include drunkenness, toxicity,
      and addiction leading to alcohol-related health and societal problems. Some of
      these effects are mediated by regulation of expression of many genes involved in
      alcohol response pathways. Analysis of the regulatory elements and biological
      interaction of the genes that show coexpression in response to alcohol may give
      an insight into how they are regulated. Fifty-two ethanol-responsive (ER) genes
      displaying differential expression in mouse brain in response to acute ethanol
      exposure were subjected to bioinformatics analysis to identify known or putative
      transcription factor binding sites and cis-regulatory modules in the promoter
      regions that may be involved in their responsiveness to alcohol. Functional
      interactions of these genes were also examined to assess their cumulative
      contribution to metabolomic pathways. Clustering and promoter sequence analysis
      of the ER genes revealed the DNA binding site for nuclear transcription factor Y
      (NFY) as the most significant. NFY also take part in the proposed biological
      association network of a number of ER genes, where these genes interact with
      themselves and other cellular components, and may generate a major cumulative
      effect on apoptosis, cell survival, and proliferation in response to alcohol. NFY
      has the potential to play a critical role in mediating the expression of a set of
      ER genes whose interactions contribute to apoptosis, cell survival, and
      proliferation, which in turn may affect alcohol-related behaviors.

PMID- 16631146
TI  - The Ramberg-Backlund reaction for the synthesis of C-glycosides, C-linked
      disaccharides and related compounds.
AB  - The discovery of the Ramberg-Backlund procedure for preparing exo-glycals from S
      glycoside dioxides, developed independently in (Old) York and New York, is
      reviewed. The methodology is successful with glucose, galactose, mannose, xylose,
      fucose, ribose, altrose, 2-deoxy-arabino-hexose (2-deoxy-glucose) and daunosamine
      derivatives, and has been used to prepare di-, tri- and tetra-substituted exo
      glycals. More recent developments, such as one-pot variants, and protecting group
      free procedures, are also covered. Synthetic applications of the exo-glycals, for
      example, to prepare beta-glycosidase inhibitors, spirocyclic glucose derivatives,
      beta-C-glycosides, C-glycosyl porphyrin glycoconjugates and C-glycosyl amino
      acids, are also discussed. Finally, applications of the Ramberg-Backlund process
      for the synthesis of known and novel C-glycosides, and in natural product
      synthesis, are reviewed.

PMID- 16631147
TI  - Determination of the structure and degree of polymerisation of fructans from
      Echinacea purpurea roots.
AB  - Highly water soluble fructans have been isolated from Echinacea purpurea (L.)
      Moench. roots by hot water extraction and precipitation at three different
      ethanol concentrations (80% v/v, 60% v/v and 40% v/v). The structure of the
      fructans has been characterised by three analytical methods: GC of silylated
      oxime derivatives and partially methylated alditol acetates, respectively, as
      well as 13C NMR analysis. The mean degree of polymerisation (mean DP) of each
      fructan has been determined by the glucose/fructose ratio. E. purpurea fructans
      represent linear inulin-type fructans with almost exclusively beta-(2-->1)-linked
      fructosyl units, terminal glucose and terminal fructose. Small proportions of
      beta-(2-->1,2-->6)-linked branch point residues were detected. The mean DP of the
      fructan fractions depends on the ethanol concentration used for precipitation:
      the lower the ethanol concentration the higher the mean DP. Corresponding results
      were found with all of the three analytical methods: 80% ethanol-insoluble
      fructan from E. purpurea shows an average mean DP of 35, 60% ethanol-insoluble
      fructan of 44 and 40% ethanol-insoluble fructan of 55. The applied methods
      provide sufficient sensitivity to determine not only the composition and
      structure but also the mean degree of polymerisation of fructans.

PMID- 16631148
TI  - Oxidative stress in aldosteronism.
AB  - Congestive heart failure (CHF) is more than a failing heart and salt-avid state.
      Also present is a systemic illness which features oxidative stress in diverse
      tissues, a proinflammatory phenotype, and a wasting of soft tissue and bone.
      Reactive oxygen and nitrogen species contribute to this illness and the
      progressive nature of CHF. Aldosteronism, an integral component of the
      neurohormonal profile found in CHF, plays a permissive role in leading to an
      altered redox state. Because of augmented urinary and fecal excretion of Ca(2+)
      and Mg(2+) and consequent decline in plasma-ionized [Ca(2+)](o) and [Mg(2+)](o)
      that accompanies aldosteronism, parathyroid glands release parathyroid hormone
      (PTH) in an attempt to restore Ca(2+) and Mg(2+) homeostasis; this includes bone
      resorption. However, PTH-mediated intracellular Ca(2+) overloading, considered a
      Ca(2+) paradox, leads to oxidative stress. This can be prevented by:
      spironolactone, an aldosterone receptor antagonist that rescues urinary and fecal
      cation losses; parathyroidectomy; amlodipine, a Ca(2+) channel blocker; N
      acetylcysteine, an antioxidant. In addition to the role played by aldosteronism
      in the appearance of secondary hyperparathyroidism is the chronic use of a loop
      diuretic, which further enhances urinary Ca(2+) and Mg(2+) excretion, and reduced
      Ca(2+) stores associated with hypovitaminosis D. This broader perspective of CHF
      and the ever increasing clinical relevance of divalent cations and oxidative
      stress raise the question of their potential management with macro- and
      micronutrients. An emerging body of evidence suggests the nutritional management
      of CHF offers an approach that will be complementary to today's pharmaceutical
      based strategies.

PMID- 16631149
TI  - NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and
      failure.
AB  - Markers of increased oxidative stress are known to be elevated following acute
      myocardial infarction and in the context of chronic left ventricular hypertrophy
      or heart failure, and their levels may correlate with the degree of contractile
      dysfunction or cardiac deficit. An obvious pathological mechanism that may
      account for this correlation is the potential deleterious effects of increased
      oxidative stress through the induction of cellular dysfunction, energetic deficit
      or cell death. However, reactive oxygen species have several much more subtle
      effects in the remodelling or failing heart that involve specific redox-regulated
      modulation of signalling pathways and gene expression. Such redox-sensitive
      regulation appears to play important roles in the development of several
      components of the phenotype of the failing heart, for example cardiomyocyte
      hypertrophy, interstitial fibrosis and chamber remodelling. In this article, we
      review the evidence supporting the involvement of reactive oxygen species and
      redox signalling pathways in the development of cardiac hypertrophy and heart
      failure, with a particular focus on the NADPH oxidase family of superoxide
      generating enzymes which appear to be especially important in redox signalling.

PMID- 16631150
TI  - Lipid-protein interactions in human plasma LDL evidenced by magnetic resonance.
AB  - Low density lipoprotein (LDL) particles exhibit extremely complex three
      dimensional structural organization which is still not understood at the
      molecular level. The aim of this study was to provide the experimental evidence
      of a direct non-covalent interaction of the protein part with the lipid matrix.
      The approach was based on the combination of (1)H NMR (600 MHz) spectroscopy with
      thiol-specific spin labeling of the protein (apoB). It is shown that the spectral
      peaks assigned to the methyl head groups of phosphatidylcholine and sphingomyelin
      in the (1)H spectra of LDL exhibit line broadening when otherwise free thiol
      groups of apoB are covalently modified by methanethiosulfonate spin label. The
      effect is similar in the presence of water soluble paramagnetic compound. These
      results indicate that fragments of apoB, which are part of the receptor binding
      region, are directly in contact with the solvated phospholipid head groups of the
      lipid matrix.

PMID- 16631151
TI  - Synthesis of fluorescent lactosylceramide stereoisomers.
AB  - The intracellular distribution of synthetic glycosphingolipids (GSLs) bearing a
      fluorophore can be monitored in living cells by fluorescence microscopy. We
      reported previously that variation in the length of the long-chain base and in
      the structure of the carbohydrate-containing polar head group of (2S,3R) (or D
      erythro-)-beta-lactosylceramide (LacCer) did not alter the mechanism of endocytic
      uptake from the plasma membrane of various mammalian cell types [Singh, R.D.,
      Puri, V., Valiyaveettil, J.T., Marks, D.L., Bittman, R., Pagano, R.E., 2003.
      Selective caveolin-1-dependent endocytosis of glycosphingolipids. Mol. Biol. Cell
      14, 3254-3265]. To extend our examination of the molecular features in LacCer
      that are responsible for its uptake by the caveolar-requiring endocytic pathway,
      we have synthesized the three unnatural stereoisomers [(2R,3R)-, (2S,3S)-, and
      (2R,3S)] of dipyrromethene difluoride (BODIPY)-LacCer. These analogues will be
      used to probe the role of stereochemistry in the long-chain base of LacCer in the
      mechanism of endocytic uptake.

PMID- 16631152
TI  - The pretreatment plasma level and diagnostic utility of M-CSF in benign breast
      tumor and breast cancer patients.
AB  - BACKGROUND: In the present study, we investigated the plasma levels of M-CSF and
      commonly accepted tumor marker (antigen CA 15-3) in breast cancer patients in
      relation to the group with benign breast tumor and to the healthy controls.
      Additionally, we compared the plasma level of M-CSF with the tumor stage of
      breast cancer and defined the diagnostic criteria: sensitivity, specificity, the
      positive and the negative predictive values. Moreover, we defined the receiver
      operating characteristics (ROC) curve for M-CSF and CA 15-3, and correlation
      between both parameters. METHODS: M-CSF and CA 15-3 were measured in 80 patients
      with breast cancer, 17 patients with benign breast tumor and in 30 healthy
      subjects. M-CSF was determined using enzyme-linked immunosorbent assay (ELISA).
      CA 15-3 was measured using a microparticle enzyme immunoassay kit (MEIA).
      RESULTS: There were statistically significant differences in the levels of
      circulating M-CSF and CA 15-3 in the breast cancer patients comparing to the
      group with benign breast tumor and to the control group. The levels of M-CSF and
      CA 15-3 were also significantly higher in patients with more advanced tumor
      stage. Statistically significant positive correlation was observed between the M
      CSF and CA 15-3 levels. The M-CSF and CA 15-3 diagnostic specificities were 95%.
      The diagnostic sensitivity (59%), the positive predictive value (97%) and the
      negative predictive value (41%) were higher for M-CSF than for CA 15-3 (48.8%,
      95% and 40.1%, respectively). The combined use of both cytokines resulted in the
      increase of the sensitivity to the range of 70%. We observed a higher range of
      the diagnostic sensitivity of M-CSF in more advanced breast tumor stage. The M
      CSF area under the ROC curve was larger (0.801) than the ROC area of CA 15-3
      (0.785). CONCLUSIONS: These results suggest that M-CSF is the good candidate for
      a breast cancer tumor marker.

PMID- 16631153
TI  - A study on medical image registration by mutual information with pyramid data
      structure.
AB  - The registration method based on mutual information is currently a popular
      technique for medical image registration, but the computation of the mutual
      information is complex and the registration speed is slow. In this work, a new
      slice accumulation pyramid (SAP) data structure was proposed to expedite the
      registration process. A numerical comparative study between the new data
      structure and the existing wavelet pyramid (WP) data structure was given, and the
      results confirmed that the new pyramid data structure was superior to the WP in
      both the calculation efficiency and the optimizing performance. Finally, SAP was
      applied to remove the artifacts between CT and MRI data sets, and the results
      showed the validation of SAP to registration of mulmodality images.

PMID- 16631154
TI  - Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural
      border and regulate cranial placodes and neural crest development.
AB  - The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in
      partially overlapping domains in the neural crest and preplacodal ectoderm. We
      examined the roles of these msx genes in early development. Disrupting individual
      msx genes causes modest variable defects, whereas disrupting all three produces a
      reproducible severe phenotype, suggesting functional redundancy. Neural crest
      differentiation is blocked at an early stage. Preplacodal development begins
      normally, but placodes arising from the msx expression domain later show elevated
      apoptosis and are reduced in size. Cell proliferation is normal in these tissues.
      Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation
      whereas misexpression of msxB dorsalizes the embryo. These effects appear to
      involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses
      ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores
      normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest
      that mutual antagonism between Msx and Dlx proteins achieves a balance of
      function required for normal preplacodal differentiation and placement of the
      neural-nonneural border.

PMID- 16631155
TI  - Role of Sox2 in the development of the mouse neocortex.
AB  - The mammalian neocortex is established from neural stem and progenitor cells that
      utilize specific transcriptional and environmental factors to create functional
      neurons and astrocytes. Here, we examined the mechanism of Sox2 action during
      neocortical neurogenesis and gliogenesis. We established a robust Sox2 expression
      in neural stem and progenitor cells within the ventricular zone, which persisted
      until the cells exited the cell cycle. Overexpression of constitutively active
      Sox2 in neural progenitors resulted in upregulation of Notch1, recombination
      signal-sequence binding protein-J (RBP-J) and hairy enhancer of split 5 (Hes5)
      transcripts and the Sox2 high mobility group (HMG) domain seemed sufficient to
      confer these effects. While Sox2 overexpression permitted the differentiation of
      progenitors into astroglia, it inhibited neurogenesis, unless the Notch pathway
      was blocked. Moreover, neuronal precursors engaged a serine protease(s) to
      eliminate the overexpressed Sox2 protein and relieve the repression of
      neurogenesis. Glial precursors and differentiated astrocytes, on the other hand,
      maintained Sox2 expression until they reached a quiescent state. Sox2 expression
      was re-activated by signals that triggered astrocytic proliferation (i.e.,
      injury, mitogenic and gliogenic factors). Taken together, Sox2 appears to act
      upstream of the Notch signaling pathway to maintain the cell proliferative
      potential and to ensure the generation of sufficient cell numbers and phenotypes
      in the developing neocortex.

PMID- 16631156
TI  - A novel noncanonical Wnt pathway is involved in the regulation of the asymmetric
      B cell division in C. elegans.
AB  - The polarities of several cells that divide asymmetrically during Caenorhabditis
      elegans development are controlled by Wnt signaling. LIN-44/Wnt and LIN-17/Fz
      control the polarities of cells in the tail of developing C. elegans larvae,
      including the male-specific blast cell, B, that divides asymmetrically to
      generate a larger anterior daughter and a smaller posterior daughter. We
      determined that WRM-1 and the major canonical Wnt pathway components: BAR-1, SGG
      1/GSK-3 and PRY-1/Axin were not involved in the control of B cell polarity.
      However, POP-1/Tcf is involved and is asymmetrically distributed to the B
      daughter nuclei, as it is in many cell divisions during C. elegans development.
      Aspects of the B cell division are reminiscent of the divisions controlled by the
      planar cell polarity (PCP) pathway that has been described in both Drosophila and
      vertebrate systems. We identified C. elegans homologs of Wnt/PCP signaling
      components and have determined that many of them appear to be involved in the
      regulation of B cell polarity. Specifically, MIG-5/Dsh, RHO-1/RhoA and LET
      502/ROCK appear to play major roles, while other PCP components appear to play
      minor roles. We conclude that a noncanonical Wnt pathway, which is different from
      other Wnt pathways in C. elegans, regulates B cell polarity.

PMID- 16631157
TI  - Single-cell mapping of neural and glial gene expression in the developing
      Drosophila CNS midline cells.
AB  - Understanding the generation of neuronal and glial diversity is one of the major
      goals of developmental neuroscience. The Drosophila CNS midline cells constitute
      a simple neurogenomic system to study neurogenesis, cell fate acquisition, and
      neuronal function. Previously, we identified and determined the developmental
      expression profiles of 224 midline-expressed genes. Here, the expression of 59
      transcription factors, signaling proteins, and neural function genes was analyzed
      using multi-label confocal imaging, and their expression patterns mapped at the
      single-cell level at multiple stages of CNS development. These maps uniquely
      identify individual cells and predict potential regulatory events and
      combinatorial protein interactions that may occur in each midline cell type
      during their development. Analysis of neural function genes, including those
      encoding peptide neurotransmitters, neurotransmitter biosynthetic enzymes,
      transporters, and neurotransmitter receptors, allows functional characterization
      of each neuronal cell type. This work is essential for a comprehensive genetic
      analysis of midline cell development that will likely have widespread
      significance given the high degree of evolutionary conservation of the genes
      analyzed.

PMID- 16631158
TI  - HNF factors form a network to regulate liver-enriched genes in zebrafish.
AB  - Defects in some of liver-enriched genes in mammals will cause liver- and/or blood
      related diseases. However, due to the fact that embryogenesis happens
      intrauterinally in the mammals, the function of these liver-enriched genes during
      liver organogenesis is poorly studied. We report here the identification of 129
      genuine liver-enriched genes in adult zebrafish and show that, through in situ
      hybridization, 69 of these genes are also enriched in the embryonic liver.
      External embryogenesis coupled with the well-established morpholino-mediated gene
      knock-down technique in zebrafish offers us a unique opportunity to study if this
      group of genes plays any role during liver organogenesis in the future. As an
      example, preliminary study using morpholino-mediated gene knock-down method
      revealed that a novel liver-enriched gene leg1 is crucial for the liver expansion
      growth. We also report the analysis of promoter regions of 51 liver-enriched
      genes by searching putative binding sites for Hnf1, Hnf3, Hnf4 and Hnf6, four key
      transcription factors enriched in the liver. We found that promoter regions of
      majority of liver-enriched genes contain putative binding sites for more than one
      HNF factors, suggesting that most of liver-enriched genes are likely co-regulated
      by different combination of HNF factors. This observation supports the hypothesis
      that these four liver-enriched transcription factors form a network in
      controlling the expression of liver-specific or -enriched genes in the liver.

PMID- 16631159
TI  - Captopril inhibits the oxidative modification of apolipoprotein B-100 caused by
      myeloperoxydase in a comparative in vitro assay of angiotensin converting enzyme
      inhibitors.
AB  - The oxidative modification of low-density lipoproteins (LDL) is a key event in
      the formation of atheromatous lesions. Indeed, oxidized derivatives accumulate in
      the vascular wall and promote a local inflammatory process which triggers the
      progression of the atheromatous plaque. Myeloperoxidase (MPO) has been mentioned
      as a major contributor to this oxidative process. It takes part in the oxidation
      both of lipids by chlorination and peroxidation and of apolipoprotein B-100.
      Based on recent observations with several anti-inflammatory and thiol-containing
      drugs, the present study was designed to test the hypothesis that anti
      hypertensive agents from the angiotensin converting enzyme (ACE) inhibitors group
      inhibit the oxidative modifications of Apo B-100 caused by MPO. Captopril,
      ramipril, enalapril, lisinopril and fosinopril were assessed by measuring: their
      inhibiting effect on the MPO/H(2)O(2)/Cl(-) system, the accumulation of compound
      II, which reflects the inhibition of the synthesis of HOCl and the LDL oxidation
      by MPO in presence of several concentrations of ACE inhibitors. Only captopril, a
      thiol-containing ACE inhibitor, was able to significantly decrease the oxidative
      modification of LDL in a dose dependent manner and this by scavenging HOCl. This
      efficient anti-hypertensive drug therefore appears to also protect against the
      atherosclerotic process by this newly documented mechanism.

PMID- 16631160
TI  - Platycodin D-induced apoptosis through nuclear factor-kappaB activation in
      immortalized keratinocytes.
AB  - Platycodi Radix is the root of Platycodon grandiflorum and it is widely used in
      the traditional Oriental medicine as an expectorant for pulmonary diseases and a
      remedy for respiratory disorders. Platycodin D is the major constituent of
      triterpene saponins in the root. This study investigates apoptosis by platycodin
      D in immortalized human keratinocytes (HaCaT). Platycodin D-induced apoptosis in
      HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase
      8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB
      kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream
      level, but not IKK-alpha. Pretreated-N-tosyl-l-phenylalanine chloromethyl ketone
      (TPCK), a potent NF-kappaB inhibitor, could suppress the induction of apoptosis
      and activation of NF-kappaB of HaCaT cells by platycodin D. We also demonstrated
      that platycodin D-mediated apoptosis of HaCaT cells upregulates Fas receptor and
      Fas ligand (FasL) expression, but did not exhibit p53 activation. HaCaT cells
      were also transfected with pFLF1, which preserves the promoter region of Fas
      receptor gene containing NF-kappaB binding site. On incubation with platycodin D,
      the NF-kappaB activity related to Fas receptor increased in a dose-dependent
      manner. Among the major transcription elements on Fas receptor and FasL promoter,
      NF-kappaB activation was shown to have an essential role in the expression of the
      death receptor such as FasL. These results suggest that platycodin D has the
      ability to induce apoptosis in HaCaT cells through the upregulation of Fas
      receptor and FasL expression via to NF-kappaB activation in the transcriptional
      level. These results demonstrate that the NF-kappaB activation plays a crucial
      role in the induction of apoptosis in human HaCaT cells on treatment with
      platycodin D.

PMID- 16631161
TI  - Requirement of the enzymatic and signaling activities of plasmin for phorbol
      ester-induced scattering of colon cancer cells.
AB  - Colon cancer progression is associated with the activation of protein kinase C
      (PKC), the downregulation of functional E-cadherin and an increased expression of
      the serine protease urokinase (u-PA) and its receptor (u-PAR). HT29-M6 intestinal
      epithelial cells represent an in vitro model to study colon cancer progression.
      These cells are induced to scatter and to invade by phorbol esters. Using
      proteolytic and cell signaling inhibitors, we show that HT29-M6 cells require
      plasminogen for the acquisition of the scattering response to PMA. Our results
      indicate that, prior to inducing a state of competency for plasminogen-dependent
      scattering, PMA triggers an ordered succession of events where upregulation of
      the activity of u-PA precedes proteolysis of u-PAR and active degradation of the
      extracellular matrix (ECM). These events poise HT29-M6 cells to a scatter
      competent state that allows the subsequent localized proteolytic activation of
      plasminogen to plasmin, required for the execution of scattering. Finally, we
      show that, in addition to its enzymatic activity directed at the degradation of
      ECM, plasmin generates an intracellular signal resulting in the phosphorylation
      of ERK 1/2. For a full motogenic activity, plasmin requires this signal since the
      use of a MEK inhibitor (PD98059) specifically blocks the plasmin-dependent phase
      of cell scattering. Our observations suggest that plasmin exerts a dual role in
      PMA-induced scattering of HT29-M6 cells, one directed extracellularly to promote
      proteolysis of the ECM and one directed to generate intracellular signaling.

PMID- 16631162
TI  - Ubc9 expression is essential for myotube formation in C2C12.
AB  - Myogenic differentiation is a fundamental biological process that involves a
      hierarchical series of events that ultimately leads to muscle-specific gene
      expression and myofiber formation. Posttranslational modifications of the
      myogenic regulatory factors have been implicated as important regulatory
      mechanisms in this process. Here we investigate whether covalent protein
      modification by a small ubiquitin-like modifier (SUMO) that is known to affect
      transcription factor activity can impact muscle differentiation. We show that the
      overall load of sumoylated proteins present in myoblasts diminishes progressively
      throughout myogenesis. Interestingly, knockdown of the SUMO-conjugating enzyme,
      Ubc9, severely compromises C2C12 muscle cell terminal differentiation. However,
      it does not affect the expression, the localization and the activation of MyoD
      and myogenin. These novel results suggest that protein sumoylation plays a
      pivotal role in myoblast differentiation and is required to regulate the activity
      of key targets downstream of MyoD and myogenin.

PMID- 16631163
TI  - Human progenitor cells isolated from the developing cortex undergo decreased
      neurogenesis and eventual senescence following expansion in vitro.
AB  - Isolation of a true self-renewing stem cell from the human brain would be of
      great interest as a reliable source of neural tissue. Here, we report that human
      fetal cortical cells grown in epidermal growth factor expressed low levels of
      telomerase and telomeres in these cultures shortened over time leading to growth
      arrest after 30 weeks. Following leukemia inhibitory factor (LIF)
      supplementation, growth rates and telomerase expression increased. This was best
      demonstrated following cell cycle synchronization and staining for telomerase
      using immunocytochemistry. This increase in activity resulted in the maintenance
      of telomeres at approximately 7 kb for more than 60 weeks in vitro. However, all
      cultures displayed a lack of oligodendrotye production, decreases in neurogenesis
      over time and underwent replicative senescence associated with increased
      expression of p21 before 70 weeks in vitro. Thus, under our culture conditions,
      these cells are not stable, multipotent, telomerase expressing self-renewing stem
      cells. They may be more accurately described as human neural progenitor cells
      (hNPC) with limited lifespan and bi-potent potential (neurons/astrocytes).
      Interestingly, hNPC follow a course of proliferation, neuronal production and
      growth arrest similar to that seen during expansion and development of the human
      cortex, thus providing a possible model neural system. Furthermore, due to their
      high expansion potential and lack of tumorogenicity, these cells remain a unique
      and safe source of tissue for clinical transplantation.

PMID- 16631164
TI  - Longitudinal non-invasive proton NMR spectroscopy measurement of vitreous lactate
      in a rabbit model of ocular hypertension.
AB  - To determine whether vitreous lactate concentrations are correlated with
      intraocular pressure (IOP) rise, retinal ganglion cell (RGC) damage, and nerve
      fiber layer (NFL) thickness decrease in a rabbit model of ocular hypertension.
      Also, to learn whether proton nuclear magnetic resonance ((1)H-NMR) spectroscopy
      can provide sequential, non-invasive in vivo measurements of vitreous lactate.
      Intra-anterior chamber injections of 20-mum latex beads were used to impede
      aqueous drainage in New Zealand White rabbits, causing an elevation of IOP. Group
      I consisted of 12 rabbits in which unilateral elevations in IOP were achieved.
      Group II consisted of 6 rabbits in which treatment did not cause a change in IOP.
      The contralateral eye served as a control in both groups. Control eyes received
      an equal volume injection of vehicle only. IOP was measured for two pre-treatment
      days and then on post-treatment days 1, 3, 5, 7, 9, 16, 23, 30, and 37. (1)H-NMR
      spectroscopy was used to measure changes in vitreous lactate concentrations that
      may be associated with the onset and progression of the pathophysiology. Post
      mortem histochemical analysis at the light microscope level was used to quantify
      changes in the retinal NFL thickness and in the numbers of RGC, and correlate
      them with IOP and percent change in lactate levels. Baseline IOP in Group I
      control and treated eyes were 12.0+/-1.9 and 12.5+/-1.3 mmHg, respectively.
      Between days 5 and 9 post-treatment, the IOP in Group I treated eyes (n=12) rose
      to 23.9+/-4.2 mmHg. IOP in the control eyes remained unchanged (12.0+/-1.6).
      Vitreous lactate levels in Group I treated eyes increased by 100%, from pre
      treatment values. Levels in control eyes remained unchanged. In Group I, IOP and
      percent change in lactate concentration in treated eyes were closely correlated
      throughout the study period (r=0.95; p< or =0.05). Group II control and treated
      eyes showed no significant changes in either IOP or lactate. Group I treated eyes
      had a reduced NFL thickness (65+/- 4 microm; n=5) at the temporal medullary ray
      (MR) compared with control eyes (45+/-6 microm). A smaller reduction was found in
      the nasal MR areas, where thickness was 53+/-3 microm in treated eyes and 66+/-4
      microm in control eyes. RGC numbers also were decreased in the treated eyes
      (241,222+/-10,920 cells) vs. 322,311+/-8726 cells in control eyes. TdT-mediated
      dUTP nick-end labeling (TUNEL) indicated that RGC loss in the treated eyes was
      most likely due to apoptosis. In vivo changes in lactate can be monitored non
      invasively over time using (1)H-NMR spectroscopy. Vitreous lactate concentrations
      increased and returned to baseline concurrently with IOP. The brief elevation in
      IOP produced a reduction in both the RGC cell numbers and in the thickness of the
      NFL.

PMID- 16631165
TI  - Integrin adhesion in regulation of lacrimal gland acinar cell secretion.
AB  - The extracellular microenvironment regulates lacrimal gland acinar cell
      secretion. Culturing isolated rabbit lacrimal gland acinar cells on different
      extracellular matrix proteins revealed that laminin enhances carbachol-stimulated
      secretion to a greater extent than other extracellular matrix proteins
      investigated. Furthermore, immunofluorescence indicated that integrin subunits,
      potentially functioning as laminin receptors are present in acinar cells. Among
      these, the integrin alpha6 and beta1 subunit mRNA expression was also confirmed
      by RT-PCR and sequence analysis. Secretion assays, which measured beta
      hexosaminidase activity released in the culture media, demonstrated that function
      blocking integrin alpha6 and beta1 monoclonal antibodies (mAbs) induce a rapid,
      transient and dose-dependent secretory response in cultured cells. To determine
      the intracellular pathways by which integrin alpha6 and beta1 mAbs could induce
      secretion, selected second messenger molecules were inhibited. Although
      inhibitors of protein kinase C and IP(3)-induced Ca(2+) mobilization attenuated
      carbachol-stimulated secretion, no effect on integrin mAb-induced release was
      observed. In addition, protein tyrosine kinases do not appear to have a role in
      transducing signals arising from mAb interactions. Our data clearly demonstrate,
      though, that cell adhesion through integrins regulates secretion from lacrimal
      gland acinar cells. The fact that the integrin mAbs affect the cholinergic
      response differently and that the integrin beta1 mAb secretion, but not the
      alpha6, was attenuated by the phosphatase inhibitor, sodium orthovanadate,
      suggests that each subunit utilizes separate intracellular signaling pathways to
      induce exocytosis. The results also indicate that the secretory response
      triggered by the beta1 integrin mAb is generated through dephosphorylation
      events.

PMID- 16631166
TI  - Aldose reductase prevents aldehyde toxicity in cultured human lens epithelial
      cells.
AB  - Aldehydes are widespread environmental and industrial compounds, which cause
      cytotoxicity, tissue damage, mutagenicity, and carcinogenicity leading to various
      disease conditions such as cardiovascular, bronchial, and visual complications.
      We have shown earlier that aldose reductase (AR) besides reducing glucose to
      sorbitol, efficiently reduces various toxic lipid-derived aldehydes, generated
      under oxidative stress, with K(m) in the physiological range. We have identified
      the role of AR in the prevention of various lipid aldehyde-induced cytotoxic
      signals leading to apoptosis in human lens epithelial cells (HLEC). HLEC were
      cultured without or with AR inhibitors followed by addition of various saturated
      and unsaturated lipid aldehydes with a carbon chain length varying from C3 to
      C10. The cell viability was assessed by cell counts and MTT assay, and apoptosis
      was measured by evaluating nucleosomal degradation and caspase-3 activation using
      specific ELISA kits. Although all the aldehydes caused apoptosis of HLEC, the
      unsaturated aldehydes were more toxic than saturated aldehydes. Inhibition of AR
      by sorbinil potentiated while the over-expression of AR prevented the apoptosis
      induced by various lipid aldehydes. AR over-expression also prevented the lipid
      aldehyde-induced activation of caspase-3, MAPK, JNK and the expression of Bcl-2
      family of proteins in HLEC. The results indicate that the lipid aldehydes
      generated under oxidative stress are cytotoxic to HLEC leading to apoptosis and
      that the reduction of lipid aldehydes by AR would prevent it.

PMID- 16631167
TI  - MUC1 splice variants in human ocular surface tissues: possible differences
      between dry eye patients and normal controls.
AB  - Mucins are highly glycosylated proteins that are vital to the maintenance of
      healthy epithelial surfaces including the ocular surface. Mucins act as
      lubricants, protectants, and mediators of signal transduction. The majority of
      the O-glycosylation sites on the transmembrane mucin MUC1 are found in a highly
      polymorphic core region containing a variable number of tandem repeats (VNTR).
      MUC1 alleles can be divided into size classes that contain small (30-45) or large
      (60-90) numbers of repeats. Although at least 12 splice variants of MUC1 have
      been found in other tissues, no splice variants have been reported in human
      ocular surface tissues. We have used RT-PCR to identify MUC1 splice variants that
      were then confirmed by sequencing. We here report the presence in some samples of
      human cornea, conjunctiva, and lacrimal gland of MUC1/B which features canonical
      splicing between exons 1 and 2 and MUC1/A, a transcript that retains 27bp from
      the 3' end of intron 1 and is predicted to add 9 amino acids to the MUC1 sequence
      upstream of the tandem repeat region. Cornea and conjunctiva both contain the
      MUC1/SEC splice variant that lacks the transmembrane domain and, therefore,
      results in a soluble, secreted form of MUC1. Cornea and conjunctiva also contain
      MUC1/Y and MUC1/Z(X) variants that lack the tandem repeat region. Cornea,
      conjunctiva, and lacrimal gland also contain a previously undescribed MUC1
      variant transcript, termed MUC1/YI, that retains 99bp from the 5' end and 27bp
      from the 3' end of the first intron, resulting in a frame shift and premature
      stop codon. This transcript is predicted to produce a novel 27 amino acid peptide
      after signal peptidase cleavage. Analysis of brush cytology samples revealed that
      the percentage of dry eye patients expressing the MUC1/A variant in the
      conjunctival epithelium is lower than in normal control donors. Western blotting
      confirmed that MUC1/A is associated with alleles containing the large size class
      of tandem repeats. Therefore, we propose that one factor in susceptibility to dry
      eye disease may be the lengths of the MUC1 VNTR in conjunctival epithelium based
      on the rationale that longer VNTR provide better lubrication and greater
      protection of the ocular surface against inflammation.

PMID- 16631168
TI  - On neural plasticity, new neurons and the postischemic milieu: an integrated view
      on experimental rehabilitation.
AB  - This review discusses actual and potential contributors to functional improvement
      after stroke injuries. Topics that will be covered are neuronal re-organization
      and sprouting, neural stem/progenitor cell activation and neuronal replacement,
      as well as the neuronal milieu defined by glia, inflammatory cells and blood
      vessel supply. It is well established that different types of neuronal plasticity
      ultimately lead to post-stroke recovery. However, an untapped potential which
      only recently has started to be extensively explored is neuronal replacement
      through endogenous or exogenous resources. Major experimental efforts are needed
      to achieve progress in this burgeoning area. The review stresses the importance
      of applying neurodevelopmental principles as well as performing a
      characterization of the role of the postischemic milieu when studying adult brain
      neural stem/progenitor cells. Integrated and multifaceted experimentation,
      incorporating actual and possible poststroke function modulators, will be
      necessary in order to determine future strategies that will ultimately enable
      considerable progress in the field of neurorehabilitation.

PMID- 16631169
TI  - Spinal cord injury-induced plasticity in the mouse--the crossed phrenic
      phenomenon.
AB  - The crossed phrenic phenomenon (CPP) describes respiratory functional plasticity
      that arises following spinal cord injury. Cervical spinal cord hemisection
      rostral to the phrenic nucleus paralyzes the ipsilateral hemidiaphragm by
      interrupting the descending flow of respiratory impulses from the medulla to
      phrenic motoneurons in the spinal cord. This loss of activity converts some
      synapses on phrenic motoneurons from a "functionally ineffective" state pre
      hemisection to a "functionally latent" state post-hemisection. If the animal is
      subjected to respiratory stress by transecting the contralateral phrenic nerve,
      this latent respiratory pathway is activated and function is restored to the
      paralyzed hemidiaphragm. The mechanisms underlying this plasticity are not well
      defined, particularly at the molecular level. Therefore, we explored whether it
      was possible to demonstrate the CPP in mice, a species amenable to a molecular
      genetic approach. We show the CPP qualitatively in mice using electromyographic
      (EMG) recordings from the diaphragm. Interestingly, our data also suggest that in
      the mouse latent fibers in the ventral funiculus ipsilateral to an anatomically
      incomplete hemisection may also play a role in the CPP. In particular, we
      examined the inter-operative delay time between the spinal cord injury and
      contralateral phrenicotomy required for a response. As the inter-operative delay
      was reduced, the proportion of mice displaying the CPP decreased from 95% for
      overnight animals, 86% in 4-8 h, to 77% for 1-2 h mice, and less than 28% for
      animals receiving a phrenicotomy under 0.5 h post-spinal cord lesion. This is the
      first study to demonstrate the CPP in mice.

PMID- 16631170
TI  - A low chronic ethanol exposure induces morphological changes in the adolescent
      rat brain that are not fully recovered even after a long abstinence: an
      immunohistochemical study.
AB  - Little is known about the morphological effects of alcoholism on the developing
      adolescent brain and its consequences into adulthood. We studied here the
      relationship between two neurotransmitter systems (the serotoninergic and
      nitrergic) and the astrocytic and neuronal cytoskeleton immediately and long
      after drinking cessation of a chronic, but low, ethanol administration.
      Adolescent male Wistar rats were exposed to ethanol 6.6% (v/v) in drinking water
      for 6 weeks and studied after ending exposure or after a 10-week recovery period
      drinking water. Control animals received water. Brain sections were processed by
      immunohistochemistry using antibodies to serotonin (5-HT); glial fibrillary
      acidic protein (GFAP); astroglial S-100b protein; microtubule associated protein
      2 (MAP-2); 200 kDa neurofilaments (Nf-200); and neuronal nitric oxide synthase
      (nNOS). The mesencephalic dorsal and median raphe nucleus (DRN; MRN) and three
      prosencephalic areas closely related to cognitive abilities (CA1 hippocampal
      area, striatum and frontal cortex) were studied by digital image analysis. 5-HT
      immunoreactivity (-ir) decreased in the DRN and recovered after abstinence and
      was not changed in the MRN. In the three prosencephalic areas, astrocytes' cell
      area (GFAP-ir cells) increased after EtOH exposure and tended to return to
      normality after abstinence, while cytoplasmic astroglial S100b protein-ir,
      relative area of MAP-2-ir and Nf-200-ir fibers decreased, and later partially
      recovered. In the striatum and frontal cortex, nNOS-ir decreased only after
      abstinence. In conclusion, in the adolescent brain, drinking cessation can
      partially ameliorate the ethanol-induced morphological changes on neurons and
      astrocytes but cannot fully return it to the basal state.

PMID- 16631171
TI  - MHC I upregulation influences astroglial reaction and synaptic plasticity in the
      spinal cord after sciatic nerve transection.
AB  - Recent studies suggested that the MHC class I expression has an important role on
      the maintenance of synaptic connections and also on neuronal/glial communication.
      IFN beta is a cytokine that influences the MHC class I expression. Therefore, the
      present work studied the effects of IFN beta on astrocyte reactivity and synaptic
      plasticity in the spinal cord. C57BL/6J adult mice were subjected to unilateral
      sciatic nerve transection after being treated with 10,000 IU of IFN beta for 1
      week. Following axotomy, they were kept under treatment for another week. After
      that, the animals were sacrificed and the lumbar spinal cords were processed for
      immunohistochemistry and electron microscopy. Placebo and non-treated axotomized
      groups were used as controls. The results showed an upregulation of GFAP
      expression in the lesioned spinal cord segments, especially in the IFN treated
      group. Interestingly, IFN treated animals, showed a grater MHC class I expression
      coupled with a decrease of synapthophysin immunoreactivity. The ultrastructure of
      synapses showed a larger pruning of presynaptic terminals in contact with alpha
      motoneurons, induced by axotomy plus IFN beta treatment. In vitro, primary
      cultures of astrocytes were treated during 1 week with IFN (non-treated, 100, 500
      and 1,000 IU/ml) and processed for immunohistochemistry (GFAP, ezrin and OX-18).
      They showed a sharp upregulation of GFAP, mostly when subjected to 500 and 1,000
      IU. The present results reinforce the role of MHC class I upregulation on the
      response to injury, both in vivo and in vitro.

PMID- 16631172
TI  - The role of NR2B containing NMDA receptor in place preference conditioned with
      morphine and natural reinforcers in rats.
AB  - It has been reported that N-methyl-D-aspartate (NMDA) receptor is implicated in
      drug addiction and antagonists of the NMDA receptor complex can inhibit the
      development and expression of conditioned place preference (CPP) induced by
      several addictive drugs, implying that this class of compounds might be
      considered as candidate for the treatment of substance abuse. To explore this
      possibility, it is important to evaluate whether the inhibitory effect of NMDA
      receptor antagonists would be confined to behaviors produced by drugs of abuse
      only, but not by natural reinforcers. According to the quantitative changes of
      NMDA receptor subunits, including NR1, NR2A, and NR2B, induced by diverse types
      of reinforcers, we chose NR2B subunit as the target of research. Experimental
      results showed that (1) an augmented expression of NR2B subunit was revealed by
      Western blotting in the nucleus accumbens (NAc) and the hippocampus in rats with
      CPP induced by morphine, but not by natural rewards such as food, novel
      environment and social interaction. (2) Ifenprodil, an antagonist highly
      selective for NR2B subunit of the NMDA receptor, produced a dose-dependent
      reduction in CPP induced by morphine and novel environment, but not that by food
      consumption and social interaction. Taking together, these findings suggested
      that NR2B containing NMDA receptor may be more involved with morphine reward
      rather than natural rewards, and that antagonism of NR2B may have a potential for
      the treatment of morphine abuse.

PMID- 16631173
TI  - The spindle assembly checkpoint: preventing chromosome mis-segregation during
      mitosis and meiosis.
AB  - Aneuploidy is a common feature of many cancers, suggesting that genomic stability
      is essential to prevent tumorigenesis. Also, during meiosis, chromosome non
      disjunction produces gamete imbalance and when fertilized result in developmental
      arrest or severe birth defects. The spindle assembly checkpoint prevents
      chromosome mis-segregation during both mitosis and meiosis. In mitosis, this
      control system monitors kinetochore-microtubule attachment while in meiosis its
      role is still unclear. Interestingly, recent data suggest that defects in the
      spindle assembly checkpoint are unlikely to cause cancer development but might
      facilitate tumour progression. However, in meiosis a weakened checkpoint could
      contribute to age-related aneuploidy found in humans.

PMID- 16631174
TI  - Intrahippocampal administration of an androgen receptor antagonist, flutamide,
      can increase anxiety-like behavior in intact and DHT-replaced male rats.
AB  - Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT),
      can decrease anxiety-like behavior; however, the mechanisms underlying these
      effects have not been established. First, we hypothesized that if T reduces
      anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then
      gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be
      reversed by systemic administration of DHT. Second, we hypothesized that if T and
      DHT reduce anxiety-like behavior in part through actions at intracellular
      androgen receptors in the hippocampus, then administration of an androgen
      receptor antagonist, flutamide, directly to the hippocampus should increase
      anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts
      that were empty or contained flutamide were applied directly to the dorsal
      hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in
      the open field, elevated plus maze, or defensive freezing tasks. GDX rats
      exhibited significantly more anxiety-like behaviors than intact or DHT-replaced
      rats. Intact and DHT-replaced rats administered flutamide to the hippocampus
      showed significantly more anxiety-like behavior than did intact and DHT-replaced
      controls. However, flutamide alone did not increase anxiety-like behavior of GDX
      rats. Together, these findings suggest that androgens can decrease anxiety-like
      behavior of male rats in part through DHT's actions at androgen receptors in the
      hippocampus.

PMID- 16631175
TI  - Prospective study of the clinico-radiological outcome of interlocked nailing in
      proximal third tibial shaft fractures.
AB  - BACKGROUND: Almost 9% of tibial shaft fractures occur in the proximal third of
      the bone. In order to address the problems of mal-alignment and late loss of
      fixation, all the specific surgical techniques described in the literature were
      used in nailing these fractures in our study. METHODS: From December 2001 to
      December 2003, 45 consecutive patients with fracture of the proximal third of the
      tibial shaft underwent nailing. The clinico-radiological outcome of these cases
      and the complications encountered were analysed. RESULTS: The average time to
      knee mobilisation and partial weight-bearing walking was 3.2 days. The fractures
      had united at an average of 4.3 months. At the last follow up, the average lower
      extremity functional score was 96%. There were seven cases of malunion (15.56%),
      with three valgus and four apex anterior angulations. Delayed union necessitated
      open bone grafting in three cases, at an average of 6.3 months. At 8 months, one
      patient with delayed union experienced nail breakage across the weakest point,
      i.e. the dynamic screw hole. He underwent reamed exchange nailing and, 3 months
      later, the fracture had united. CONCLUSION: Meticulous intramedullary nailing of
      fractures of the proximal third of the tibial shaft, using all current surgical
      principles and techniques, has excellent clinico-radiological outcome and is
      relatively safe. We recommend a nail similar to a Sirus nail, but with a more
      proximal bend of the nail and no dynamic interlocking screw hole.

PMID- 16631176
TI  - Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in
      endometrial cancer.
AB  - OBJECTIVE: To see whether laparoscopy provides exact staging and effective
      treatment of endometrial cancer patients, compared with total abdominal
      hysterectomy, with shorter hospital stay, prompter recovery, and better quality
      of life. METHOD: This retrospective study identified 110 patients scheduled for
      surgery for early-stage endometrial cancer. Fifty-five (50%) were treated by
      laparoscopic-assisted vaginal hysterectomy (LAVH) and 55 (50%) by total abdominal
      hysterectomy (TAH). All patients underwent pelvic lymphadenectomy. The majority
      of patients (79%) had stage I disease. RESULTS: The mean number of lymph nodes
      removed was 17 for the LAVH group and 18.5 for the TAH group (p = 0.294).
      Compared with TAH, LAVH required a significantly longer operating time (220 vs.
      175 min; p < 0.01); but shorter hospital stay (4 vs. 8.5 days; p < 0.001) and
      less estimated blood loss (177 cm3 vs. 285 cm3; p = 0.02). Overall, there were
      fewer post-operative complications in the LAVH group (6 vs. 11 cases; p < 0.001).
      Three TAH patients (5.4%) had recurrence of disease. No LAVH patients had
      recurrences and all are currently disease-free. CONCLUSION: These findings
      suggest LAVH gives correct staging of endometrial disease, like TAH, but with
      fewer complications and a slightly longer operating time.

PMID- 16631177
TI  - Computer-aided vs. tutor-delivered teaching of exposure therapy for phobia/panic:
      randomized controlled trial with pre-registration nursing students.
AB  - BACKGROUND: Exposure therapy is effective for phobic anxiety disorders (specific
      phobias, agoraphobia, social phobia) and panic disorder. Despite their high
      prevalence in the community, sufferers often get no treatment or if they do, it
      is usually after a long delay. This is largely due to the scarcity of healthcare
      professionals trained in exposure therapy, which is due, in part, to the high
      cost of training. Traditional teaching methods employed are labour intensive,
      being based mainly on role-play in small groups with feedback and coaching from
      experienced trainers. In an attempt to increase knowledge and skills in exposure
      therapy, there is now some interest in providing relevant teaching as part of pre
      registration nurse education. Computers have been developed to teach terminology
      and simulate clinical scenarios for health professionals, and offer a potentially
      cost effective alternative to traditional teaching methods. OBJECTIVE: To test
      whether student nurses would learn about exposure therapy for phobia/panic as
      well by computer-aided self-instruction as by face-to-face teaching, and to
      compare the individual and combined effects of two educational methods,
      traditional face-to-face teaching comprising a presentation with discussion and
      questions/answers by a specialist cognitive behaviour nurse therapist, and a
      computer-aided self-instructional programme based on a self-help programme for
      patients with phobia/panic called FearFighter, on students' knowledge, skills and
      satisfaction. DESIGN: Randomised controlled trial, with a crossover, completed in
      2 consecutive days over a period of 4h per day. PARTICIPANTS: Ninety-two mental
      health pre-registration nursing students, of mixed gender, age and ethnic origin,
      with no previous training in cognitive behaviour therapy studying at one UK
      university. RESULTS: The two teaching methods led to similar improvements in
      knowledge and skills, and to similar satisfaction, when used alone. Using them in
      tandem conferred no added benefit. Computer-aided self-instruction was more
      efficient as it saved teacher preparation and delivery time, and needed no
      specialist tutor. CONCLUSION: Computer-aided self-instruction saved almost all
      preparation time and delivery effort for the expert teacher. When added to past
      results in medical students, the present results in nurses justify the use of
      computer-aided self-instruction for learning about exposure therapy and
      phobia/panic and of research into its value for other areas of health education.

PMID- 16631179
TI  - Comprehensive combinatory standard correction: a calibration method for handling
      instrumental drifts of gas chromatography-mass spectrometry systems.
AB  - The current work describes a new method, the comprehensive combinatory standard
      correction (CCSC), for the correction of instrumental signal drifts in GC-MS
      systems. The method consists in analyzing together with the products of interest
      a mixture of n selected internal standards, and in normalizing the peak area of
      each analyte by the sum of standard areas and then, select among the summation
      operator sigma(p = 1)(n)C(n)p possible sums, the sum that enables the best
      product discrimination. The CCSC method was compared with classical techniques of
      data pre-processing like internal normalization (IN) or single standard
      correction (SSC) on their ability to correct raw data from the main drifts
      occurring in a dynamic headspace-gas chromatography-mass spectrometry system.
      Three edible oils with closely similar compositions in volatile compounds were
      analysed using a device which performance was modulated by using new or used
      dynamic headspace traps and GC-columns, and by modifying the tuning of the mass
      spectrometer. According to one-way ANOVA, the CCSC method increased the number of
      analytes discriminating the products (31 after CCSC versus 25 with raw data or
      after IN and 26 after SSC). Moreover, CCSC enabled a satisfactory discrimination
      of the products irrespective of the drifts. In a factorial discriminant analysis,
      100% of the samples (n = 121) were well-classified after CCSC versus 45% for raw
      data, 90 and 93%, respectively after IN and SSC.

PMID- 16631178
TI  - Skin alterations of intact skin and risk factors associated with pressure ulcer
      development in surgical patients: a cohort study.
AB  - BACKGROUND: The pathology literature suggests three types of pressure ulcer with
      six possible mechanisms leading to tissue breakdown. A limitation of current
      evidence is the difficulty in replicating the clinical situation and in
      determining the point at which a tissue assault becomes irreversible and results
      in tissue breakdown. In particular clinical observations of alteration in darkly
      pigmented skin, blanching erythema, non-blanching erythema and non-blanching
      erythema with other skin changes including induration, oedema, pain, warmth or
      discolouration have not been assessed in relation to subsequent skin/tissue loss
      and their pathophysiological and aetiological importance is not fully understood.
      OBJECTIVES: To assess the validity of clinical signs of erythema as predictors of
      pressure ulcer development and identify variables which independently are
      predictive of Grade 2 pressure ulcer development. DESIGN: Prospective cohort
      study. PARTICIPANTS: 109 general, vascular and orthopaedic hospital patients,
      aged over 55 years with an expected length of stay of 5 days were recruited. Of
      these 97 were pressure ulcer free at baseline and/or had complete follow-up
      including 59 women and 38 men with a median age of 75 years (range 55-95).
      SETTING: Single centre large acute UK NHS hospital. METHODS: To identify clinical
      signs of erythema predictive of skin loss, the odds of pressure ulcer development
      were examined using logistic regression. To identify variables independently
      predictive of Grade 2 pressure ulcer development logistic regression modeling was
      undertaken. RESULTS: There was significantly increased odds of pressure ulcer
      development associated with non-blanching erythema (7.98, p=0.002) and non
      blanching erythema with other skin changes (9.17, p=0.035). Logistic regression
      modeling identified non-blanching erythema, pre-operative albumin, weight loss,
      and intra-operative minimum diastolic blood pressure, as independent predictors
      of Grade > or =2 pressure ulcer development. CONCLUSIONS: Non-blanching erythema
      with or without other skin changes is distinct from normal skin/blanching
      erythema and is associated with subsequent pressure ulcer development.

PMID- 16631180
TI  - Determination of lanthanides in international geochemical reference materials by
      reversed-phase high-performance liquid chromatography using error propagation
      theory to estimate total analysis uncertainties.
AB  - The weighted least-squares (WLS) regression method was successfully applied to
      establish calibration curves with variable amounts of lanthanides ranging from
      0.002 to 0.430 microg. These curves were employed for the analysis of 13
      lanthanides (La-Nd, Sm-Tb, and Ho-Lu) in 12 international geochemical reference
      materials (IGRM). The separation of the lanthanide group was achieved in
      approximately 15 min. Dysprosium could not be determined in IGRM because of its
      co-elution with Yttrium. A linear gradient program of alpha-HIBA eluent with a
      concentration ranging from 0.05 to 0.5 M (0.1 M OS, pH 3.8 with NH(4)OH, and a
      flow-rate of 1.0 ml/min) was employed. The detection was performed with a UV-vis
      system at 658 nm using a post-column reagent of Arsenazo III (0.5 ml/min). With
      this set of RP-HPLC conditions together with the use of both the ordinary least
      squares (OLS) and the WLS regressions, we report the results of the measurements
      along with the total propagated uncertainties in individual concentration values.
      The uncertainties were obtained by combining standard errors in both regression
      parameters (slope and intercept) with those related to the chromatographic peak
      areas. The straight-line slopes and intercepts calculated by the WLS method
      provided not only considerably smaller errors than the conventional OLS method
      but also a much better estimation of the limits of detection. The concentrations
      calculated were compared with the "most probable" concentration values of these
      reference materials reported in the literature. Statistically significant
      agreement was consistently observed between the HPLC data and the literature
      values. The total uncertainties in estimated concentration values for the WLS
      were consistently smaller than the respective errors for the OLS.

PMID- 16631181
TI  - Secondary isotope effects in liquid chromatography behaviour of 2H and 3H
      labelled solutes and solvents.
AB  - The separation of solutes that differ only in the extent of isotopic substitution
      of their hydrogen atoms, using either mixtures of isotopically non-modified or
      perdeuterated solvents as mobile phases, is described. The occurrence of a
      secondary isotope effect is demonstrated in reversed-phase liquid chromatography,
      which is independent of the nature of the stationary phase (different octadecyl
      bonded silicas, an embedded alkylamide-bonded silica, as well as one polymeric
      stationary phase were tested), and the water content and the nature of organic
      modifier of the mobile phase. The separation of 24 structurally different
      isotopologue pairs (apolar compounds and polar compounds with exchangeable or non
      exchangeable hydrogen atoms) is examined using reversed-phase liquid
      chromatography. It is found that the greater the number of isotopically
      substituted hydrogen atoms in a given organic solute, the better is the
      separation of a particular isotopologue pair. The single secondary isotope effect
      is shown to be dependent on the number of isotopic substitutions. The greater the
      number of these substitutions, the smaller is the single isotope effect. The
      single secondary isotope effect is higher for aromatic hydrocarbons than for
      aliphatic hydrocarbons. A secondary isotope effect is also observed in chiral
      chromatography and normal-phase liquid chromatography, as well as on changing the
      nature of the substituting isotope, i.e.: tritium instead of deuterium. Thus, we
      have demonstrated that the total secondary isotopic effect for hydrogen/tritium
      is higher than for hydrogen/deuterium. This isotope effect involves only the
      consequences of changes in interactions due to nuclear motions. Overall this
      study confirms the predominance of hydrophobic effects in retention processes in
      reversed-phase liquid chromatography. In reversed-phase liquid chromatography, a
      secondary isotope effect related to mobile phase composition is also observed.
      The behaviour of deuterium oxide and water in mobile phases of the same
      composition (%, w/w) is compared. Independent of the nature of the organic
      modifier (methanol, acetonitrile or ethanol), the effect of replacing H2O with
      2H2O in the mobile phase, is an increase in the retention factors and an
      improvement in the chromatographic resolution of isotopologue pairs. This
      increase in the resolution is not accompanied by a change in the chromatographic
      selectivity. The measurement of liquid-liquid extraction coefficients proves that
      the effect is mainly due to the modification of the phase ratio. In general the
      effect of 2H-labelled solvents (2H2O and C2H3CN) as mobile phase components,
      compared to their isotopically non-modified isomers, can be rationalized on the
      basis of their lower polarisabilities. Overall the use of perdeuterated rather
      than isotopically non-modified solvents as mobile phase components leads to the
      most efficient separation systems.

PMID- 16631182
TI  - Enhancement of molecular-shape selectivity in high-performance liquid
      chromatography through multi-anchoring of comb-shaped polymer on silica.
AB  - Poly(octadecylacrylate) having plural trimethoxysilyl groups in the side chain
      (co-ODA(n)) was newly synthesized and immobilized onto silica through these
      groups. The liquid chromatographic behavior of silica-supported co-ODA(n) (Sil-co
      ODA(n)) was investigated and compared with that of Sil-ODA(n), in which
      poly(octadecylacrylate) was immobilized through a terminal trimethoxy group at
      one side of the polymer main chain. Sil-co-ODA(n) showed higher selectivity for
      molecular shape, especially molecular planarity of PAHs than Sil-ODA(n).

PMID- 16631183
TI  - Comprehensive screening of anabolic steroids, corticosteroids, and acidic drugs
      in horse urine by solid-phase extraction and liquid chromatography-mass
      spectrometry.
AB  - This paper reports two highly efficient liquid chromatography-mass spectrometry
      (LC-MS) methods for the screening of anabolic steroids, corticosteroids, and
      acidic drugs for the purpose of doping control in equine sports. Sample
      extraction was performed using a mixed-mode C8-SCX solid-phase extraction (SPE)
      cartridge. The first eluted fraction (acidic/neutral fraction) was base-washed
      and the resulting organic extract was used for the screening of anabolic steroids
      and corticosteroids by LC-MS using multiple reaction monitoring (MRM) in the
      positive electrospray ionisation (ESI) mode. The remaining aqueous extract was re
      adjusted to pH 6 and acidic drugs were recovered by liquid/liquid extraction.
      Detection was again achieved using LC-MRM but in the negative ESI mode. A total
      of 40 anabolic steroids and corticosteroids, and over 50 acidic drugs, including
      some cyclooxygenase-2 (COX-2) inhibitors, oxicams, anti-diabetics, sedatives,
      diuretics and Delta(9)-tetrahydro-11-norcannabinol-9-carboxylic acid, could be
      covered by the two LC-MS methods. Both methods utilized a high efficiency
      reversed-phase column (3.3 cm L x 2.1 mm I.D. with 3 microm particles) coupled
      with a fast-scanning triple-quadrupole mass spectrometer to achieve fast
      turnaround times. The overall turnaround times for both methods were 10 min,
      inclusive of post-run and equilibration times.

PMID- 16631184
TI  - Spectroscopic investigation of the adsorption mechanisms of polyacrylamide
      polymers onto iron oxide particles.
AB  - The mechanisms of high-molecular-weight polyacrylamide nonionic homopolymer and
      25 mol% anionic acrylate-substituted copolymer adsorption onto iron oxide
      particles were investigated via DRIFT and UV-vis spectroscopies at three pH
      values (6, 8.5, and 11). While electrostatic interactions play an important role
      in charged polymer adsorption, this information is not spectroscopically
      available. At pH values above and below pH 8.5 (the isoelectric point for the
      anionic polymer), bidentate chelation and hydrogen bonding were the main
      adsorption mechanisms. At the isoelectric point, monodentate chelation was
      observed to be the main mode of adsorption, along with hydrogen bonding. For the
      nonionic polymer, in all cases, hydrogen bonding through the carbonyl group was
      the main mode of adsorption. The adsorption of both polymers conformed well to
      the Freundlich model, suggesting that the adsorbed polymer amount increases with
      increasing polymer concentration up to 7500 g/t solid, rather than approaching
      monolayer coverage. Spectroscopic evidence was found to suggest that hydrolysis
      of nonionic polyacrylamide occurs at high pH.

PMID- 16631185
TI  - Structure of montmorillonite cointercalated with stearic acid and octadecylamine:
      modeling, diffraction, IR spectroscopy.
AB  - Structural analysis of Na-montmorillonite co-intercalated with octadecylamine and
      stearic acid was carried out using combination of experiment: X-ray powder
      diffraction and IR spectroscopy with molecular modeling (force field
      calculations) in Cerius(2) modeling environment. Results of structure analysis
      revealed the chemical reaction of guest compounds leading to the formation of
      octadecylammonium stearate. This reaction may occur even before the intercalation
      out of the interlayer space of montmorillonite. The presence of octadecylammonium
      stearate in the samples was clearly confirmed by IR spectroscopy and X-ray
      diffraction. Present results also showed that: (1) Stearic acid itself does not
      intercalate into Na-montmorillonite; (2) cointercalation with octadecylamine led
      to the formation of octadecylammonium stearate, which was successfully
      intercalated into the interlayer space of montmorillonite, and (3) Na
      montmorillonite intercalated with octadecylammonium stearate does not create a
      stable structure. Intercalated samples in ambient conditions undergo gradual
      decomposition, accompanied by the release of octadecylammonium stearate from the
      interlayer space and rearrangement of the interlayer structure. Co-intercalation
      of STA and ODA to lower the octadecylamine content and consequently to suppress
      the unfavorable effect of amine groups on the polymer matrix in nanocomposite,
      was investigated.

PMID- 16631186
TI  - An improved method for determining zeta potential and pore conductivity of porous
      materials.
AB  - An improved method based on streaming potential and streaming current was
      proposed to determine zeta potential and surface conductance of porous material
      simultaneously. In the electrokinetic generation mode, a resistor is connected to
      the generator and by measuring the voltage drop across resistors with different
      resistance, a true streaming current can be determined. The zeta potential and
      surface conductivity can be obtained simultaneously from their relation to
      streaming potential and streaming current. The electrode and ion concentration
      polarization effects during the measurement were also discussed. The resistance
      from channel ends to electrodes, which has typically been ignored in the
      literature, was shown to have a significant influence on the calculated zeta
      potential and surface conductance. Ignorance of this resistance would lead to
      underestimation of both zeta potential and surface conductance values.

PMID- 16631187
TI  - Core-shell structured SiO2@YVO4:Dy3+/Sm3+ phosphor particles: sol-gel preparation
      and characterization.
AB  - Spherical SiO(2) particles have been coated with YVO(4):Dy(3+)/Sm(3+) phosphor
      layers by a Pechini sol-gel process, leading to the formation of core-shell
      structured SiO(2)@YVO(4):Dy(3+)/Sm(3+) particles. X-ray diffraction (XRD),
      Fourier-transform IR spectroscopy, field emission scanning electron microscopy
      (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL) spectra
      as well as lifetimes were used to characterize the resulting
      SiO(2)@YVO(4):Dy(3+)/Sm(3+) core-shell phosphors. The obtained core-shell
      phosphors have perfect spherical shape with narrow size distribution (average
      size ca. 300 nm), smooth surface and non-agglomeration. The thickness of shells
      could be easily controlled by changing the number of deposition cycles (20 nm for
      one deposition cycle). The core-shell particles show strong characteristic
      emission from Dy(3+) for SiO(2)@YVO(4):Dy(3+) and from Sm(3+) for
      SiO(2)@YVO(4):Sm(3+) due to an efficient energy transfer from YVO(4) host to
      them. The PL intensity of Dy(3+) and Sm(3+) increases with raising the annealing
      temperature and the number of coating cycles.

PMID- 16631188
TI  - Colloid dispersion in a uniform-aperture fracture.
AB  - This research investigates the dispersion of colloids through fracture systems by
      exploring experimentally and numerically the transport and dispersion of 1.0-,
      0.11-, and 0.043-mum diameter fluorescent carboxylate-modified microspheres and
      chloride at various flow rates through variable-length, synthetic Plexiglas
      fractures (flow cells). A dimensionless number describing each experiment is
      varied by changing the colloid size, flow rate, and fracture length. Surface
      characteristics of the microspheres and Plexiglas favor repulsive interactions,
      thereby minimizing the chance of colloid filtration and remobilization. Full
      recovery of the colloids is typically observed, thereby supporting the assumption
      of negligible colloid filtration. In comparison to chloride transport, there is
      increased tailing for colloid plumes traveling through the flow cell. This
      increased tailing is attributed to Taylor dispersion phenomena (dispersion due to
      an advection gradient). In the synthetic fractures investigated here, colloid
      dispersion due to the velocity gradient is evident, but fully developed Taylor
      conditions are not realized. A particle-tracking algorithm is run inversely to
      estimate the effective dispersion rate for the colloid plume in each experiment
      as a function of the experimental parameters (flow rate, fracture length, and
      colloid size). Results suggest that the log of the effective dispersion rate of
      the colloid plume increases linearly with the log of the dimensionless number
      comprising experimental parameters.

PMID- 16631189
TI  - Adsorption characteristics of bisphenol-A in aqueous solutions onto hydrophobic
      zeolite.
AB  - The adsorption behavior of bisphenol-A, which is a hydrophobic organic compound
      and also listed as one of endocrine disrupting chemicals, from aqueous solution
      onto hydrophobic zeolite at 25 degrees C have been studied using a batch
      adsorption process in terms of a pseudo-second-order equation and three common
      isotherms (i.e., the Langmuir, Freundlich, and Redlich-Peterson). The pore
      properties of the Y-type zeolite have been determined using N2 adsorption
      desorption isotherms, indicating that it is a supermicroporous adsorbent
      associated with a lower percentage of mesopores. Based on the kinetic model the
      effects of particle size, initial bisphenol-A concentration, initial solution pH,
      and adsorbent dosage on the adsorption rate constant and equilibrium capacity
      have been estimated, showing that the adsorption process could be simulated well
      by the simplified kinetic model. From the data on the equilibrium adsorption
      capacities obtained by fitting the pseudo-second-order model, the adsorption
      isotherm could be better described by the three-parameter Redlich-Peterson model
      than by the two-parameter models (i.e., the Langmuir and Freundlich).

PMID- 16631190
TI  - Generation current of charged micelles in nonaqueous liquids: measurements and
      simulations.
AB  - Electrically charged species in nonaqueous media still hold many questions.
      Recent studies and applications show the need for a better understanding of the
      origin and nature of these charged species. Transient current measurements have
      been used to study the conductivity of nonaqueous liquid containing charged
      inverse micelles. At small time scales (1-100 ms) drift and diffusion of charged
      species are the main contributions to the measured current. At larger timescales
      (above 1 s) a nonzero quasi steady-state current at high voltages (above 0.5 V)
      remains. This indicates that besides drift and diffusion an additional process
      occurs. The dependence of the quasi steady-state current on the applied voltage,
      micelle concentration, and device thickness has been investigated. Experimental
      results have been compared to simulations and analytical calculations. It is
      concluded that the quasi steady-state current results from a bulk
      disproportionation reaction between neutral micelles that generates charged
      micelles. And therefore this technique allows for direct quantification of the
      reaction kinetics from which the charged species originate.

PMID- 16631191
TI  - The characterisation of rough particle contacts by atomic force microscopy.
AB  - An Atomic Force Microscopy (AFM) reverse imaging technique has been used to
      determine the contact zone topography of glass and UO3 particles in contact with
      flat mica substrates. A method is proposed that uses this topography to determine
      an effective asperity radius of curvature for the contacting particle.
      Application of the method has been found to be consistent with established
      contact mechanics models, for both glass and UO3 particle probes that present
      significantly different surface roughness. The method proposed is straightforward
      to apply and offers a greater insight into the influence of particle micro- and
      nano-roughness on adhesion. This is important for applications that rely on the
      control of granular flow such as pellet or tablet manufacture.

PMID- 16631192
TI  - In situ formation of dispersed palladium nanoparticles in microemulsion:
      efficient reaction system for ligand-free Heck reaction.
AB  - The ligand-free Heck reaction catalyzed by Pd(OAc)2 performed well in a TX10 oil
      in-water microemulsion. TEM proved in situ formation distributed palladium
      nanoparticles in the microemulsion. The role of TX10 in the reaction system is
      the palladium nanoparticles reducing agent and stabilizer. The effect of reaction
      parameters on the Heck reaction conversion were discussed. The results indicated
      that the aqueous phase concentration, the base concentration, and the temperature
      played key roles in the conversion of the reaction. Iodobenzene was converted to
      the corresponding trans-stilbene quantitatively within 90-150 min. Therefore, the
      heptane/TX 10/butanol/water/propylene glycol microemulsion containing in situ
      formed palladium nanoparticles was a very efficient catalyst system for the
      ligand-free Heck reaction.

PMID- 16631193
TI  - Effects of isolated coronary artery ectasia on electrocardiographic parameters
      reflecting ventricular heterogeneity.
AB  - Isolated coronary ectatic but otherwise normal epicardial coronary arteries are
      an infrequent angiographic finding. We sought to determine whether coronary
      artery ectasia (CAE) may alter QT-interval duration and dispersion. The study
      population consisted of 24 patients with isolated CAE and otherwise normal
      epicardial coronary arteries (group 1) and sex- and age-matched subjects with
      atypical chest pain and otherwise normal coronary flow (group 2). Both groups
      underwent a routine standard 12-lead surface electrocardiogram recorded at 50
      mm/s during rest. QT dispersion (QTd), corrected QT (QTc), and corrected QT
      dispersion (QTcd) were calculated. Distribution of sex, age, body mass index, and
      cardiac risk factors were similar in the 2 groups. Mean heart rate was similar in
      the 2 groups (74 +/- 10 vs 70 +/- 7, P > .05). In group 1, QTd, QTcd, and QTc
      were significantly higher than those of group 2 (QTd, 40 +/- 17 vs 29 +/- 10
      milliseconds [P < .05]; QTcd, 43 +/- 19 vs 30 +/- 10 milliseconds [P < .05]; QTc,
      410 +/- 21 vs 397 +/- 19 milliseconds [P < .05]). In conclusion, CAE was found to
      be associated with prolonged QT interval and increased QTd. Microvascular
      dysfunction and/or ischemia may be responsible mechanisms.

PMID- 16631194
TI  - Cloning of B cell lymphoma-associated antigens using modified phage-displayed
      expression cDNA library and immunized patient sera.
AB  - Active immunization of follicular lymphoma patients with idiotypic vaccines
      elicits antigen-specific antibody responses, T-cell responses, and antitumor
      effects. We hypothesized that these vaccinated patients could generate tumor
      specific immune responses, not only against idiotype, but also against other
      tumor-associated antigens (TAA) by a mechanism of epitope spreading. To identify
      potential antigens, a phage surface expressed cDNA library derived from primary
      tumor cells was screened with sera from idiotype-vaccinated patients. Consistent
      with our hypothesis, we identified two immunogenic peptides (FL-aa-7 and 18),
      unrelated to idiotype, which were recognized by postvaccine sera but not by
      prevaccine or normal human sera. These peptide sequences derived from the 5'
      untranslated regions of the human GTPase, IMAP family member 7 gene (FL-aa-7) and
      an alternative reading frame of U1-snRNP 70 (FL-aa-18), respectively, suggesting
      that epitope spreading had occurred.

PMID- 16631195
TI  - Rapid synthesis of a register-specific heterotrimeric type I collagen helix
      encompassing the integrin alpha2beta1 binding site.
AB  - We report a rapid method to synthesize cystine cross-linked heterotrimeric
      collagenous peptides. They can be engineered to favour one particular axial
      alignment of the strands, called the register of the helix. Here, the sequence of
      the constituent peptides contains 18 residues of "guest" collagen type I sequence
      flanked by N and C-terminal (Gly-Pro-Pro)5 "host" modules which ensure helicity.
      Further C-terminal residues include appropriately spaced cysteine residues and
      alanine to provide the necessary flexibility for helix formation. The cross
      linking reaction and subsequent separation protocols have been designed for any
      inserted collagen sequence that does not contain a cysteine residue. Mass
      spectrometry and ion-exchange chromatography allow us to distinguish between
      different disulphide-bonded species and to monitor the formation of side
      products. Starting peptide can be recovered simply from the reaction mixture by
      reduction and separation. Yields are typically 30%, working on a 10 mg scale. 15N
      1H NMR and platelet adhesion studies show that the peptide heterotrimers
      presented here can reshuffle to cover all three axial registers. Less flexible
      spacers between the disulphide linkages and the helix will restrict each
      heterotrimer to one register only.

PMID- 16631196
TI  - The structure of an inverting GH43 beta-xylosidase from Geobacillus
      stearothermophilus with its substrate reveals the role of the three catalytic
      residues.
AB  - beta-D-Xylosidases are glycoside hydrolases that catalyze the release of xylose
      units from short xylooligosaccharides and are engaged in the final breakdown of
      plant cell-wall hemicellulose. Here we describe the enzyme-substrate crystal
      structure of an inverting family 43 beta-xylosidase, from Geobacillus
      stearothermophilus T-6 (XynB3). Each XynB3 monomeric subunit is organized in two
      domains: an N-terminal five-bladed beta-propeller catalytic domain, and a beta
      sandwich domain. The active site possesses a pocket topology, which is mainly
      constructed from the beta-propeller domain residues, and is closed on one side by
      a loop that originates from the beta-sandwich domain. This loop restricts the
      length of xylose units that can enter the active site, consistent with the exo
      mode of action of the enzyme. Structures of the enzyme-substrate (xylobiose)
      complex provide insights into the role of the three catalytic residues. The
      xylose moiety at the -1 subsite is held by a large number of hydrogen bonds,
      whereas only one hydroxyl of the xylose unit at the +1 subsite can create
      hydrogen bonds with the enzyme. The general base, Asp15, is located on the alpha
      side of the -1 xylose sugar ring, 5.2 Angstroms from the anomeric carbon. This
      location enables it to activate a water molecule for a single-displacement attack
      on the anomeric carbon, resulting in inversion of the anomeric configuration.
      Glu187, the general acid, is 2.4 Angstroms from the glycosidic oxygen atom and
      can protonate the leaving aglycon. The third catalytic carboxylic acid, Asp128,
      is 4 Angstroms from the general acid; modulating its pK(a) and keeping it in the
      correct orientation relative to the substrate. In addition, Asp128 plays an
      important role in substrate binding via the 2-O of the glycon, which is important
      for the transition-state stabilization. Taken together, these key roles explain
      why Asp128 is an invariant among all five-bladed beta-propeller glycoside
      hydrolases.

PMID- 16631197
TI  - Role of E.coli NusA in phage HK022 Nun-mediated transcription termination.
AB  - The 109 amino acid residue Nun protein expressed from prophage HK022 excludes
      superinfecting phage lambda by arresting transcription on the lambda chromosome
      near the lambdanut sites. In vitro, the Nun N terminus binds to nascent
      lambdanutRNA, whereas the C terminus interacts with RNA polymerase and DNA
      template. Escherichia coli host factors, NusA, NusB, NusE (S10), and NusG,
      stimulate Nun-arrest. NusA binds the Nun C terminus and enhances formation of the
      Nun-nutRNA complex. Because of these in vitro activities of NusA, and since a
      nusA mutation (nusAE136K) blocked Nun in vivo, we assumed that NusA was required
      for Nun activity. However, using a nusAts strain, we find that NusA is required
      for termination at nutR but not at nutL. Furthermore, nusAE136K is dominant to
      nusA(+) for Nun-arrest, both in vitro and in vivo. NusAE136K shows increased
      affinity for Nun and, unlike NusA(+), can readily be recovered in a ternary
      complex with Nun and nutRNA. We propose NusAE136K suppresses Nun-arrest when it
      is a component of the transcription elongation complex, perhaps, in part, by
      blocking interactions between the Nun C terminus and RNA polymerase and DNA. We
      also find that in contrast to Nun-arrest, antitermination by lambda N requires
      NusA.

PMID- 16631198
TI  - Impedance cardiography: a potential monitor for hemodialysis.
AB  - BACKGROUND: Impedance cardiography (ICG) technology has improved dramatically,
      and at least one device now can give a measurement of fluid status by using
      thoracic fluid content (TFC), along with cardiac output (CO) and cardiac index
      (CI). With a built-in sphygmomanometer cuff, it can also provide blood pressure
      (BP) and systemic vascular resistance index (SVRI). A currently available small
      portable ICG that provides reliable measures of fluid status could be an ideal
      noninvasive monitor for hemodialysis (HD), with the potential of helping avoid
      significant hemodynamic instability during HD. METHODS: A case series of patients
      with chronic renal failure was studied while undergoing HD using ICG (BioZ,
      CardioDynamics, Int. Corp., San Diego, CA). Parameters recorded at 15-min
      intervals included TFC, CI, BP (systolic, diastolic, and mean arterial), SVRI,
      and heart rate. Using the Pearson method, the percentage changes in each of the
      parameters during the HD session were correlated to the amount of fluid removed
      (FR), normalized to body weight. RESULTS: Forty-one patients were enrolled, but
      six patients were excluded due to incomplete data; therefore, 35 patients (13 men
      and 22 women) formed the basis of the analysis. The age range was 28 to 87 (mean
      55.1 +/- 16.1) years. The amount of FR was 2.88 +/- 1.13 L (37.3 +/- 14.6 ml/kg).
      TFC decreased in all patients during the HD session (average reduction 12.7 +/- 8
      kohms(-1)); whereas all other hemodynamic parameters showed both increases and
      decreases. The correlation of change in TFC with FR was moderate (r = 0.579, P =
      0.0003); other hemodynamic parameters showed a poor correlation with FR. Neither
      the standard hemodynamic parameters nor the ICG device's special parameters were
      able to identify the five patients in this series who experienced significant
      hemodynamic instability or intradialytic hypotension. CONCLUSION: TFC, measured
      easily and noninvasively using ICG, correlates with the amount of fluid removed
      during HD. In comparison with the other hemodynamic parameters measured, TFC
      changed most consistently with fluid removal. Whether or not serial TFC
      measurements in a given patient at different HD sessions can guide the extent of
      FR will require additional study. This compact, easily operated, and nonobtrusive
      ICG device with the capability for continuously providing the standard
      hemodynamic parameters plus CO, TFC, and standard limb lead electrocardiography
      could replace current monitoring systems.

PMID- 16631199
TI  - Toll-like receptor-4 message is up-regulated in lipopolysaccharide-exposed rat
      lung pericytes.
AB  - BACKGROUND: Pericytes are multifunctional, polymorphic perivascular cells that
      lie within the microvessel basal lamina, are located on the abluminal side of
      endothelial cells, and are thought to play a regulatory role in capillary leak
      observed in sepsis. Toll-Like receptor 4 (TLR-4) has been implicated as the
      proximal transmembrane receptor for the LPS/CD 14 complex during the activation
      of lipopolysacharide (LPS)-induced sepsis. It is our hypothesis that TLR-4 is
      present on lung pericytes and is up-regulated in response to LPS. METHODS: Rat
      microvascular lung pericytes were isolated and cultured. Cells from passage 3-5
      were used and treated with LPS (control, 10 ng/mL, and 100 ng/mL) for 18 h.
      Immunostaining and immunoblotting were performed to detect the presence of CD-14,
      TLR-2, and TLR-4. Real-time polymerase chain reaction was used to analyze the
      presence and quantity of mRNA for CD-14, TLR-2, and TLR-4. RESULTS:
      Immunostaining and immunoblotting revealed the presence of CD-14, TLR-2, and TLR
      4 in pericytes from each treatment group, and real-time polymerase chain reaction
      confirmed the presence of mRNA for CD-14, TLR-2, and TLR-4. An increase in the
      mRNA was observed in CD-14, TLR-2, and TLR-4 in the presence of increasing LPS 4
      h after treatment. At 18 h after LPS treatment, a decrease in mRNA was noted.
      CONCLUSIONS: The up-regulation of TLR-4 in the presence of increasing LPS
      suggests its importance in pericyte LPS-induced activation. Pericyte TLR-4
      recognition of LPS could play a role in capillary leak seen in sepsis. These data
      also demonstrates that pericytes, once thought to be passive participants in the
      inflammatory cascade, may be active members.

PMID- 16631200
TI  - Local arginine supplementation results in sustained wound nitric oxide production
      and reductions in vascular endothelial growth factor expression and granulation
      tissue formation.
AB  - OBJECTIVE: The goal of this work was to test the functional role of L-arginine in
      promotion of nitric oxide (NO) production and the vigorous granulation tissue
      formation characteristic of this wound model. BACKGROUND: Therapeutic use of
      supplemental arginine has been proposed as a safe and efficacious method to
      produce NO from nitric oxide synthase (NOS) and to produce proline and polyamines
      from arginase to improve wound healing. Although NO appears to be necessary to
      promote wound healing, the preferential metabolism of arginine to NO via NOS 2
      may be detrimental if maintained beyond the initial days of healing. METHODS: A
      ventral hernia, surgically created in the abdominal wall of 12 swine, was
      repaired with silicone sheeting and skin closure. Osmotic infusion pumps,
      inserted in remote subcutaneous pockets, continuously delivered saline (n = 6) or
      L-arginine (n = 6) into the wound environment. Granulation tissue thickness was
      determined by ultrasonography. Fluid was aspirated serially from the wound
      compartment for measurements of nitrite/nitrate (NOx), vascular endothelial
      growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and amino
      acid concentrations. On day 14, the animals were sacrificed and the abdominal
      wall was harvested for immunohistochemical and molecular analysis. RESULTS: In
      animals receiving saline, a nearly linear four-fold increase in granulation
      tissue thickness was measured during the 14-day interval. In contrast,
      quantitative ultrasound analysis detected significant reductions in L-arginine
      infused granulation tissue thickness compared with controls between days 4 and 14
      (P < 0.05). Wound vessel count and luminal vascular surface area estimates
      derived from image analysis of histological sections were two- to three-fold
      lower in the L-arginine animals compared with controls (P < 0.05). Significant
      and sustained increases in wound fluid NOx levels were noted in L-arginine
      animals compared to saline controls (230 microM versus 75 microM at day 14, P <
      0.05). Conversely, late VEGF levels (days 11 to 14) were reduced in the L
      arginine animals compared to controls (7500 pg/ml versus 10,000 pg/ml at day 11,
      P < 0.05; 7250 pg/ml versus 11,101 pg/ml at day 14, P < 0.05). Arginine
      concentrations remained two- to four-fold greater in L-arginine treated animals
      compared with controls over the entire time course (P < 0.05). There were no
      significant differences in concentrations of ornithine, citrulline, or proline
      noted between groups over the 14-day period. Finally, TGF-beta1 levels were
      unaffected by L-arginine treatment. CONCLUSION: Although NO appears to be
      necessary for granulation tissue formation, early supplemental arginine may
      disturb the reciprocal regulation of NOS 2 and arginase, leading to the
      preferential metabolism of arginine to excess NO rather than ornithine, with
      consequent reductions in angiogenesis and granulation tissue formation.

PMID- 16631201
TI  - Infected chronic wounds show different local and systemic arginine conversion
      compared with acute wounds.
AB  - BACKGROUND: Several experimental studies have shown the importance of arginine in
      wound healing. However, little is known about its role in human wound healing. In
      this study, we investigated arginine metabolism in impaired wound healing.
      MATERIALS AND METHODS: Twenty patients with chronic wounds and 10 patients with
      acute wounds were included in a prospective study. Amino acids, nitrate/nitrite,
      and arginase concentrations were determined in plasma and wound fluid using high
      performance liquid chromatography and enzyme-linked immunosorbent assay. Chronic
      wounds were divided into two groups: noninfected chronic wounds (n = 11) and
      infected chronic wounds (n = 9), based on quantitative bacterial analysis of
      wound fluid samples. RESULTS: Plasma arginine levels, next to total plasma amino
      acid levels, were significantly decreased in patients with infected chronic
      wounds compared with patients having acute or noninfected wounds. Citrulline and
      ornithine levels were significantly increased in infected chronic wounds and
      related to decreased nitrate/nitrite levels, whereas wound fluid arginine levels
      were similar in all groups. In addition, wound fluid arginase levels of infected
      chronic wounds were significantly enhanced. CONCLUSIONS: This study demonstrates
      that patients with infected chronic wounds have decreased plasma arginine levels
      and suggests enhanced arginine conversion in the wound. In contrast to
      noninfected chronic wounds, arginine seems to be mainly metabolized by arginase
      in infected chronic wounds. In conclusion, our hypothesis is that impaired wound
      healing is related to an altered arginine usage.

PMID- 16631202
TI  - Active leukocyte crawling in microvessels assessed by digital time-lapse
      intravital microscopy.
AB  - OBJECTIVE: The ability of active movement is an important feature of leukocytes.
      Here, we used a hybrid technique that combines intravital microscopy and digital
      time-lapse video microscopy to investigate the physiology and molecular
      mechanisms of intravascular leukocyte movement. METHODS: Intravital microscopy of
      mesenteric venules was performed in male, Wistar rats using digital video
      recording and time-lapse image compression. The leukocyte movement and
      extravasation were analyzed after local application of TNF-alpha, after blockade
      of endothelial (anti-ICAM-1 antibody) and leukocyte (anti-CD18 antibody) adhesion
      molecules. Additionally, the migratory activity of isolated leukocytes in
      collagen gel was analyzed and compared with their intravascular locomotion.
      RESULTS: Adherent leukocytes showed an active intraluminal crawling along the
      endothelial lining. Most permanent stickers (84 +/- 13%) crawled actively on the
      intraluminal site of venules. Baseline measurement of leukocyte crawling velocity
      yielded an average 9.0 +/- 1.8 mum/min that was not significantly different from
      crawling velocity of extravascular leukocytes (8.9 +/- 4.5 mum/min). The maximum
      distance of leukocyte crawling observed was 150 microm. The maximum time of
      crawling was 15 min. Intraluminal crawlers traveled over a mean distance of 35 +/
      17 mum with the average duration of 5.4 +/- 1.4 min. Under unstimulated
      conditions, almost all crawling leukocytes detached from the endothelium and did
      not migrate through the vascular wall. TNF-alpha induced a significant increase
      of leukocyte extravasation. Anti-ICAM-1 and anti-CD18 antibodies significantly
      reduced leukocyte crawling. The proportion of isolated migrating leukocytes in
      collagen gel (87% +/- 6%) was not significantly different from the percentage of
      intravascular crawling leukocytes in vivo. CONCLUSIONS: The method of digital
      time-lapse intravital microscopy represents an advantageous technology for the
      investigation of intravascular, transendothelial, and extravascular migration of
      leukocytes. Using this technology, we showed that leukocyte-endothelial
      interactions are an active and dynamic process. This process involves long-time
      (several minutes) crawling of leukocytes along the endothelium and, finally,
      detachment from the endothelium. Intravascular leukocyte crawling reflects the
      migratory potential of circulating leukocytes and strongly depends on the
      expression of adhesion molecules. For extravasation, an additional pro
      inflammatory stimulus is required.

PMID- 16631203
TI  - Functional magnetic resonance imaging and cognition at the very early stage of
      MS.
AB  - Dysfunction of high controlled information processing is present in patients with
      multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is
      that disruption of communication inside large-scale cortical networks, occurring
      as a consequence of white matter damage, may constitute the anatomical substrate
      of cognitive impairment at the very early stage of MS. Disturbance of
      interregional synchronization might be the main pathogenic factor in controlled
      information processing deficiency in early MS. Preliminary functional MRI studies
      (fMRI) have provided important clues to corroborate the connectivity hypotheses.
      First, brain connectivity assessed by fMRI has brought new data about the
      influence of diffuse white matter damage on connectivity efficiency inside large
      scale networks. These studies have suggested that connectivity disturbances occur
      inside the working memory network in patients at the very early stage of MS and
      appear related to the extent of structural white matter damage. Also, fMRI
      studies have suggested that patients may partially compensate for connectivity
      impairment by a greater cognitive control. Such a compensatory mechanism could
      limit the determinant functional impact of diffuse white matter damage on high
      controlled information processing.

PMID- 16631204
TI  - Anti-Hu-associated paraneoplastic limbic encephalitis presenting as rapidly
      progressive non-convulsive status epilepticus.
AB  - We report a 68-year-old woman who developed refractory non-convulsive generalized
      status epilepticus secondary to anti-Hu antibodies, detected by
      immunofluorescence and confirmed by Western immunoblotting. The patient presented
      with rapidly evolving impairment in consciousness and electroencephalographic
      evidence of lateralized pseudoperiodic sharp-wave discharges. Ataxia and sensory
      neuropathy developed within the first two weeks. To our knowledge, this is the
      first description of a very rapidly progressive non-convulsive status epilepticus
      of paraneoplastic origin. Serum anti-Hu antibodies deserve to be considered among
      the investigations required in the evaluation of rapidly progressive epileptic
      syndromes even when little or no imaging abnormalities are found.

PMID- 16631205
TI  - DYT1 mutations amongst adult primary dystonia patients in Singapore with review
      of literature comparing East and West.
AB  - BACKGROUND: Dystonia is a heterogenous group of movement disorders whose clinical
      spectrum is very wide. At least 13 different genes and gene loci have been
      reported. While a 3-bp deletion in the DYT1 gene is the most frequent cause of
      early limb-onset, generalized dystonia, it has also been found in non-generalized
      forms of sporadic dystonia. An 18-bp deletion in the DYT1 gene has also been
      reported. OBJECTIVES: We screened for the 3-bp and 18-bp deletions in the DYT1
      gene among our sporadic, adult-onset primary dystonia patients in Singapore. We
      reviewed the literature to compare the frequency of DYT1 mutation between the
      East and the West. METHODS: We screened 54 patients with primary dystonia (focal:
      n=41; segmental: n=11; multifocal: n=1; generalized: n=1) for the deletions in
      the DYT1 gene. A careful review of all published literature on DYT1 screening
      among sporadic, non-familial, non-Ashkenazi Jewish patients was done. RESULTS: We
      did not detect any mutations in the exon 5 of the DYT1 gene in any of our
      patients. The frequency of DYT1 mutation amongst Asians (1.0%) was comparable to
      the West (1.56%) (p=NS). CONCLUSIONS: DYT1 mutations are uncommon amongst adult
      primary dystonia patients in Singapore.

PMID- 16631206
TI  - Structural and functional surrogates of cognitive impairment at the very early
      stage of multiple sclerosis.
AB  - Following our previous reports based on parametric MRI methods (T(2)-weighted
      MRI, statistical mapping analysis of magnetization transfer ratio images and
      functional MRI) applied to a population of 18 patients with clinically isolated
      syndrome suggestive of multiple sclerosis, we have reviewed the possible
      structural and functional surrogates of MS that could explain the subtle
      cognitive impairment related to attention and working memory deficits evaluated
      with paced auditory serial addition test (PASAT). We propose that the brain
      substrates underlying cognitive impairment observed at the very early stage of MS
      are multifactorial. Several components could influence PASAT performances in
      patients: i) the extent of diffuse white matter damage, ii) the location of
      visible and non visible lesions, iii) the connectivity efficiency between distant
      brain functional areas involved in working memory processes and iv) the cortical
      reorganization. Nevertheless, individually, each of these parameters may have few
      influences on PASAT performance in patients. Using a multiregression model built
      with independent MR parameters, a very good evaluation of PASAT scores has been
      obtained in this limited number of patients explaining 90% of the variance. In
      conclusion, the different aspects of tissue and functional pathological brain
      underpinnings must be accounted to monitor accurately new therapeutic strategies
      for the treatment of early cognitive deficits related to MS.

PMID- 16631207
TI  - Insulin resistance, inflammation, and cognition in Alzheimer's Disease: lessons
      for multiple sclerosis.
AB  - Insulin resistance (reduced ability of insulin to stimulate glucose utilization)
      is common in North American and Europe, where as many as one third of all older
      adults suffer from prodromal or clinical type 2 diabetes mellitus. It has long
      been known that insulin-resistant conditions adversely affect general health
      status. A growing body of findings suggests that insulin contributes to normal
      brain functioning and that peripheral insulin abnormalities increase the risk for
      memory loss and neurodegenerative disorders such as Alzheimer's disease.
      Potential mechanisms for these effects include insulin's role in cerebral glucose
      metabolism, peptide regulation, modulation of neurotransmitter levels, and
      modulation of many aspects of the inflammatory network. An intriguing question is
      whether insulin abnormalities also influence the pathophysiology of multiple
      sclerosis (MS), an autoimmune disorder characterized by elevated inflammatory
      biomarkers, central nervous system white matter lesions, axonal degeneration, and
      cognitive impairment. MS increases the risk for type 1 diabetes mellitus.
      Furthermore, the lack of association between MS and type 2 diabetes may suggest
      that insulin resistance affects patients with MS and the general population at
      the same alarming rate. Therefore, insulin resistance may exacerbate phenomena
      that are common to MS and insulin-resistant conditions, such as cognitive
      impairments and elevated inflammatory responses. Interestingly, the
      thiazolidinediones, which are used to treat patients with type 2 diabetes, have
      been proposed as potential therapeutic agents for both Alzheimer's disease and
      MS. The agents improve insulin sensitivity, reduce hyperinsulinemia, and exert
      anti-inflammatory actions. Ongoing studies will determine whether
      thiazolidinediones improve cognitive functioning for patients with type 2
      diabetes or Alzheimer's disease. Future studies are needed to examine the effects
      of thiazolidinediones on patients with MS.

PMID- 16631208
TI  - A probability model predicting initiation efficiency of retroviral vectors with
      two primer-binding sites.
AB  - Initiation of reverse transcription in retroviruses occurs at a specific point in
      the viral genome, called the primer-binding site (PBS). The efficiency of reverse
      transcription initiation is not known. We previously published a paper describing
      reverse transcription of the retroviral vector S-2PBS containing two PBSs.
      Reverse transcription of this vector results in a provirus with one of four
      possible structures, depending, in part, on the PBSs used to initiate reverse
      transcription. Using Southern blotting analyses of DNA from infected cells, we
      measured the relative proportions of proviruses with different structures.
      Although the analysis allowed us to detect multiple initiation events occurring
      in a single virion, the measurement of frequency of such events was not possible.
      In this paper, we have built a probability model, which describes the reverse
      transcription process and predicts the outcomes of different initiation
      scenarios. By fitting the predicted outcomes to the observed data, we have been
      able to estimate the initiation efficiency in this system as approximately 0.4
      initiation per PBS. In addition, we show that even though multiple models of
      reverse transcription can explain the observed data, all of these models predict
      approximately the same initiation efficiency. This initiation efficiency is
      discussed in relation to general replication strategies of retroviruses.

PMID- 16631209
TI  - Prediction of potential thermostable proteins in Xylella fastidiosa.
AB  - The average protein (E+K)/(Q+H) ratio in organisms has already been demonstrated
      to have a strong correlation with their optimal growth temperature. Employing the
      Thermo-Search web tool, we used this ratio as a basis to look for thermostable
      proteins in a mesophile, Xylella fastidiosa. Nine proteins were chosen to have
      their three-dimensional structures modeled by homology, using mainly proteins
      from mesophiles as templates. Resulting models featured a high number of
      hydrophobic interactions, a property that has been previously associated with
      thermostability. These results demonstrate the interesting possibility of using
      the (E+K)/(Q+H) ratio to find individual thermostable proteins in mesophilic
      organisms.

PMID- 16631210
TI  - Effects of some neurosteroids injected into some brain areas of WAG/Rij rats, an
      animal model of generalized absence epilepsy.
AB  - Neurosteroids are synthesized in the brain and have been demonstrated to modulate
      various cerebral functions. Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20
      one), a naturally occurring neurosteroid, and ganaxolone (3alpha-hydroxy-3beta
      methyl-5alpha-pregnan-20-one), a synthetic derivative, are two neurosteroids
      acting as positive allosteric modulators of the GABA(A) receptor complex acting
      on a specific steroid recognition site. Both agents antagonize generalized tonic
      clonic seizures in various animal models of epilepsy. Pregnenolone sulphate
      (3beta-hydroxy-5alpha-pregnen-20-one 3-sulphate; PS) is a negative allosteric
      modulator of GABA(A) receptors and a positive modulator of the NMDA receptors. We
      have evaluated the effects of such compounds in a genetic animal model of absence
      epilepsy, the WAG/Rij rat. Animals were chronically implanted with five
      frontoparietal cortical electrodes for electrocorticogram (EEG) recordings and
      bilateral guide cannulae into specific brain areas of the cortico-thalamic
      circuit in order to evaluate the effects of these compounds on the number and
      duration of epileptic spike-wave discharges (SWDs). The focal and bilateral
      microinjection of the two GABA(A) positive modulators into some thalamic nuclei
      (nucleus ventralis posteromedialis, nucleus reticularis thalami, nucleus
      ventralis posterolateralis was usually able to significantly worsen the
      occurrence of SWDs in WAG/Rij rats. Whereas both compounds were able to reduce
      the number and duration of SWDs when microinjected into the peri-oral region of
      the primary somatosensory cortex. The effects of PS were more complex depending
      on both the dose and the site of administration, generally, at low doses in
      thalamic nuclei and cortex, PS induced an increase of absence activity and a
      reduction at higher doses. These findings suggest that neurosteroids might play a
      role in absence epilepsies and that it might depend on the involvement of
      specific neuronal areas.

PMID- 16631211
TI  - 3-hydroxypyridazine 1-oxides as carboxylate bioisosteres: a new series of subtype
      selective AMPA receptor agonists.
AB  - Three positional isomers (compounds 1, 2, and 3) of 1-uracilylalanine
      (willardiine) based on a 3-hydroxypyridazine 1-oxide scaffold with an alanine
      side-chain at positions 4 (1), 5 (2) or 6 (3) were tested for binding to
      recombinant homomeric AMPA receptor (AMPA-R) subtypes GluR1-4, as well for
      excitatory activity on the rat cortical wedge preparation. 1 had approximately 30
      times higher affinity than willardiine while showing a similar selectivity
      profile, i.e. 22-fold selectivity for GluR1/2 over GluR3/4. The GluR1-4
      affinities of 3 were similar to 1, however, its 31-fold selectivity for GluR1/2
      over GluR3/4 is the highest yet observed among azine-based glutamate analogues.
      The non-isosteric congener 2 showed weaker binding to AMPA-Rs. In the cortical
      wedge, 1 evokes similar responses to AMPA, while 3 and 2 are 10- and 100-fold
      weaker, respectively. Dose-response curves on Xenopus laevis oocytes expressing
      GluR1-4(flip) confirmed that 1 and 3 are potent GluR1/2 receptor agonists
      (EC(50)s from 0.26 to 1.7microM) but are 10- to 160-fold less potent at GluR3/4.
      The structures, potencies and selectivities of this new class of AMPA agonists
      are compared with those of willardiine, 5-fluorowillardiine and azawillardiine,
      referring to the binding mode observed in the crystal structure of willardiine
      bound to GluR2-S1S2. The results indicate that the 3-hydroxypyridazine 1-oxide
      moiety can function as an outstanding carboxylate mimic at AMPA-Rs, leading the
      way to further fine-tuning of subtype selectivity. This little-explored molecular
      motif may find wider application in medicinal chemistry.

PMID- 16631212
TI  - Effects of chronic nicotine administration and its withdrawal on striatal
      FosB/DeltaFosB and c-Fos expression in rats and mice.
AB  - DeltaFosB, a member of Fos family of transcription factors, is implicated in
      behavioural responses and synaptic plasticity induced by abused drugs. We studied
      the expressions of FosB/DeltaFosB and c-Fos immunohistochemically in two
      dopaminergic brain areas, nucleus accumbens (NAcc) and caudate-putamen (CPu). In
      mice neither 2- nor 7-week oral nicotine treatment induced expression of long
      lived DeltaFosB isoforms although during the treatment in the NAcc FosB/DeltaFosB
      expression was increased as was c-Fos in the CPu. In rats given nicotine
      subcutaneously once daily for 5days FosB/DeltaFosB expression was elevated in the
      NAcc still after 24-h withdrawal suggesting accumulation of DeltaFosB but in the
      CPu neither FosB/DeltaFosB nor c-Fos expression was altered. Thus, in rats
      repeated nicotine administration seems mainly affect the NAcc paralleling with
      the evidence that nicotine stimulates preferentially mesolimbic dopamine system.
      Also, repeated nicotine induced behavioural sensitization in rats agreeing with
      suggested role of DeltaFosB in the development of psychomotor sensitization.
      However, in mice given nicotine via drinking fluid although striatal fosB and c
      fos were activated by nicotine even after 7-week treatment no evidence of
      accumulation of long-lived DeltaFosB was found suggesting perhaps a species
      difference or more likely a role for the manner of administration.

PMID- 16631213
TI  - A brief review of the recent evolution of the human mouth in physiological and
      nutritional contexts.
AB  - One of the defining characteristics of humans, one that could also explain our
      species' success, is probably our ability to cook food. A brief review of the
      literature suggests several adaptations of the mouth can be interpreted to
      support this. All probably enhance the efficiency of the physical treatment of
      food in the mouth.

PMID- 16631214
TI  - Influence of nitric oxide on morphine-induced amnesia and interactions with
      dopaminergic receptor agents.
AB  - The interactions of dopaminergic receptors and nitric oxide (NO) with morphine
      induced memory of passive avoidance have been investigated in mice. Pre-training
      administration of morphine (1, 3 and 5 mg/kg, s.c.) dose-dependently decreased
      the learning of a one-trial passive avoidance task. Pre-training administration
      of L-arginine, a nitric oxide precursor (50, 100 and 200 mg/kg, i.p.), alone did
      not affect memory formation. The drug (100 and 200 mg/kg) decreased significantly
      amnesia induced by pre-training morphine (5 mg/kg). Pre-training administration
      of L-NAME (N(G)-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS)
      inhibitor (20 and 30 mg/kg, i.p.), dose-dependently impaired memory formation. In
      addition, co-pretreatment of different doses of L-NAME (10, 20 and 30 mg/kg) with
      lower dose of morphine (1 mg/kg), which did not induce amnesia by itself, caused
      inhibition of memory formation. Pre-training administration of apomorphine, a
      dopaminergic receptor agonist (0.25, 0.5 and 1 mg/kg, i.p.), alone also did not
      affect memory formation, but morphine-induced amnesia was significantly inhibited
      by pretreatment with apomorphine (0.5 and 1 mg/kg, 5 min, i.p.). On the other
      hand, the inhibition of morphine-induced amnesia by L-arginine (200 mg/kg, i.p.)
      was significantly decreased by pretreatment with different doses of dopamine D1
      receptor antagonist, SCH 23390 (0.001, 0.01 and 0.1 mg/kg, i.p.) or D2 receptor
      antagonist, sulpiride (12.5, 25, 50 and 100 mg/kg, i.p.). However, the dopamine
      receptor antagonists could not affect memory formation by themselves. It may be
      concluded that the morphine-induced impairment of memory formation can be
      prevented by nitric oxide donor and, in this effect, dopaminergic mechanism is
      involved.

PMID- 16631215
TI  - Consumption of alcohol by sows in a choice test.
AB  - The domestic pig (Sus scrofa domesticus) has been proposed as an animal model for
      human alcoholism because pigs have been observed to consume alcohol voluntarily
      to a state of intoxication and to exhibit tolerance and physical dependence.
      However, it has not been established whether pigs can develop psychological
      dependence on alcohol. We hypothesised that feed-restricted, stall-housed
      pregnant sows fed alcohol non-voluntarily for 5 weeks would develop a preference
      for alcohol and retain this preference after removal of alcohol from the diet. We
      fed crossbred commercial sows (n=10) 280 ml of 95% ethanol mixed with 0.91 kg of
      feed and 720 ml of water twice daily for 5 weeks during the first trimester of
      pregnancy. Control sows (n=7) received dextrose in their feed as a caloric
      control, and water was added to give the feed a consistency similar to that of
      the alcohol-treated feed. Immediately before and after 5 weeks of alcohol or
      dextrose treatment and 3 weeks later, after termination of alcohol or dextrose
      treatment, we evaluated sow diet preference by comparing the amount of alcohol
      supplemented, dextrose-supplemented and plain feed consumed during a 5-min choice
      test. Contrary to our hypothesis, there was no treatment effect on sow diet
      preference. Both alcohol-treated and control sows ate less of the alcohol diet
      than the other two diets in all choice tests. They did not discriminate between
      the plain and dextrose diets. We conclude that 5 weeks of non-voluntary
      consumption of alcohol in feed did not produce a preference for alcohol in
      pregnant sows, either during treatment or after withdrawal, thus providing no
      evidence for the development of psychological dependence on alcohol under these
      conditions.

PMID- 16631216
TI  - Steroidal saponins from the aerial parts of Tribulus alatus Del.
AB  - Six steroidal glycosides (1-6) were isolated from the aerial parts of Tribulus
      alatus Del. (Zygophyllaceae), together with one known cholestane, one spirostane,
      and six flavonol glycosides. Among them, 1 and 2 possess a furostane-type
      aglycone, 3 and 6 a cholestane structure, and 4 and 5 a spirostane skeleton.
      Their structural elucidation was accomplished by extensive spectroscopic methods
      including 1D ((1)H, (13)C, (13)C DEPT, TOCSY, ROESY) and 2D NMR experiments (DQF
      COSY, HSQC, HMBC) as well as ESI-MS analysis.

PMID- 16631217
TI  - Steroids and receptors in canine mammary cancer.
AB  - The aims of this study were to investigate the serum and tissue content of
      androgens and estrogens in canine inflammatory mammary carcinomas (IMC) as well
      as in non-inflammatory malignant mammary tumors (MMT), and assessed the
      immunoexpression of estrogen and androgen receptors using immunohistochemistry.
      Profiles for the androgens dehydroepiandrosterone (DHEA), androstenedione (A4),
      and testosterone (T), and for the estrogens 17beta estradiol (E2) and estrone
      sulphate (SO4E1) were measured both in tissue homogenates and in serum of MMT and
      IMC by EIA techniques in 42 non-inflammatory malignant mammary tumors (MMT) and
      in 14 inflammatory mammary carcinomas (IMC), prospectively collected from 56
      female dogs. Androgen receptor (AR) and estrogen receptor alpha (ERalpha) and
      beta (ERbeta) expression was studied using immunohistochemistry (strepavidin
      biotin-peroxidase method) in samples of 32 MMT and 14 IMC, and counted by a
      computer image analyzer. IMC serum and tissue levels of androgens were
      significantly higher than MMT levels. Tissue content of estrogens was also
      significantly higher in IMC than in MMT. Serum values of SO4E1 were significantly
      higher in IMC, but serum levels of E2 were significantly lower in IMC compared to
      MMT cases. Medium-high androgen receptor intensity was observed in 64.28% of IMC
      and 40.62% of MMT. No important differences were found between ERalpha expression
      in IMC (100% negative) and MMT (90% negative). ERbeta and AR were intensely
      expressed in highly malignant inflammatory mammary carcinoma cells. To our
      knowledge, this is the first report relative to AR immunohistochemistry in canine
      mammary cancer and to estrogens or androgens in serum of dogs with benign or
      malignant mammary tumors.

PMID- 16631218
TI  - Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4
      vinylcyclohexene.
AB  - The occupational chemical 4-vinylcyclohexene (VCH) destroys small preantral
      ovarian follicles in mice following repeated daily dosing. The cell survival gene
      bcl-2 is thought to protect against follicular death during embryogenesis because
      primordial follicle numbers in newborn bcl-2 overexpressing (OE) mice are greater
      than in wild-type (WT) controls. Thus, this study was designed to determine if
      overexpression of bcl-2 protects against VCH-induced follicle loss during
      embryonic development. Pregnant bcl-2 OE or WT mice were dosed (p.o.) daily with
      VCH (500 mg/kg) or sesame oil (vehicle control) on days 8-18 of pregnancy.
      Ovaries were collected from moms and female pups on pup postnatal day (PND) 8.
      Nonpregnant OE and WT females were also treated with VCH (500 mg/kg p.o.) or
      vehicle and evaluated in the same manner. As previously reported, ovaries from
      PND8 OE female pups contained 50% more primordial follicles than WT pups (P <
      0.05). Unlike WT pups, relative to vehicle controls, in utero exposure to VCH
      resulted in a reduction in primordial (25% of control), primary (38% of control),
      and secondary (33% of control) follicles in ovaries of OE pups (P < 0.05). VCH
      had no significant effect on follicle numbers in OE or WT moms. Conversely, in
      nonpregnant adults, VCH did not affect WT mice but caused loss of primordial (55%
      of control), primary (51% of control), and secondary (69% of control) follicles
      in OE mice (P < 0.05). These results demonstrate that bcl-2 overexpression does
      not protect against, but instead increases susceptibility to VCH-induced follicle
      loss in transplacentally exposed or in nonpregnant mice.

PMID- 16631219
TI  - Complete nucleotide sequence of a P2 family lysogenic bacteriophage, varphiMhaA1
      PHL101, from Mannheimia haemolytica serotype A1.
AB  - The 34,525 nucleotide sequence of a double-stranded DNA bacteriophage (phiMhaA1
      PHL101) from Mannheimia haemolytica serotype A1 has been determined. The phage
      encodes 50 open reading frames. Twenty-three of the proteins are similar to
      proteins of the P2 family of phages. Other protein sequences are most similar to
      possible prophage sequences from the draft genome of Histophilus somni 2336.
      Fourteen open reading frames encode proteins with no known homolog. The P2
      orthologues are collinear in phiMhaA1-PHL101, with the exception of the phage
      tail protein gene T, which maps in a unique location between the S and V genes.
      The phage ORFs can be arranged into 17 possible transcriptional units and many of
      the genes are predicted to be translationally coupled. Southern blot analysis
      revealed phiMhaA1-PHL101 sequences in other A1 isolates as well as in serotype
      A5, A6, A9, and A12 strains of M. haemolytica, but not in the related organisms,
      Mannheimia glucosida or Pasteurella trehalosi.

PMID- 16631220
TI  - Sendai virus defective-interfering genomes and the activation of interferon-beta.
AB  - The ability of some Sendai virus stocks to strongly activate IFNbeta has long
      been known to be associated with defective-interfering (DI) genomes. We have
      compared SeV stocks containing various copyback and internal deletion DI genomes
      (and those containing only nondefective (ND) genomes) for their ability to
      activate reporter genes driven by the IFNbeta promoter. We found that this
      property was primarily due to the presence of copyback DI genomes and correlated
      with their ability to self-anneal and form dsRNA. The level of IFNbeta activation
      was found to be proportional to that of DI genome replication and to the ratio of
      DI to ND genomes during infection. Over-expression of the viral V and C proteins
      was as effective in blocking the copyback DI-induced activation of the IFNbeta
      promoter as it was in reducing poly-I/C-induced activation, providing evidence
      that these DI infections activate IFNbeta via dsRNA. Infection with an SeV stock
      that is highly contaminated with copyback DI genomes is thus a very particular
      way of potently activating IFNbeta, presumably by providing plentiful dsRNA under
      conditions of reduced expression of viral products which block the host antiviral
      response.

PMID- 16631221
TI  - Comparative mechanistic studies of de novo RNA synthesis by flavivirus RNA
      dependent RNA polymerases.
AB  - Flavivirus protein NS5 harbors the RNA-dependent RNA polymerase (RdRp) activity.
      In contrast to the RdRps of hepaci- and pestiviruses, which belong to the same
      family of Flaviviridae, NS5 carries two activities, a methyltransferase (MTase)
      and a RdRp. RdRp domains of Dengue virus (DV) and West Nile virus (WNV) NS5 were
      purified in high yield relative to full-length NS5 and showed full RdRp activity.
      Steady-state enzymatic parameters were determined on homopolymeric template
      poly(rC). The presence of the MTase domain does not affect the RdRp activity.
      Flavivirus RdRp domains might bear more than one GTP binding site displaying
      positive cooperativity. The kinetics of RNA synthesis by four Flaviviridae RdRps
      were compared. In comparison to Hepatitis C RdRp, DV and WNV as well as Bovine
      Viral Diarrhea virus RdRps show less rate limitation by early steps of short
      product formation. This suggests that they display a higher conformational
      flexibility upon the transition from initiation to elongation.

PMID- 16631222
TI  - Functional impact of HIV coreceptor-binding site mutations.
AB  - The bridging sheet region of the gp120 subunit of the HIV-1 Env protein interacts
      with the major virus coreceptors, CCR5 and CXCR4. We examined the impact of
      mutations in and adjacent to the bridging sheet region of an X4 tropic HIV-1 on
      membrane fusion and entry inhibitor susceptibility. When the V3-loop of this Env
      was changed so that CCR5 was used, the effects of these same mutations on CCR5
      use were assayed as well. We found that coreceptor-binding site mutations had
      greater effects on CXCR4-mediated fusion and infection than when CCR5 was used as
      a coreceptor, perhaps related to differences in coreceptor affinity. The
      mutations also reduced use of the alternative coreceptors CCR3 and CCR8 to
      varying degrees, indicating that the bridging sheet region is important for the
      efficient utilization of both major and minor HIV coreceptors. As seen before
      with a primary R5 virus strain, bridging sheet mutations increased susceptibility
      to the CCR5 inhibitor TAK-779, which correlated with CCR5 binding efficiency.
      Bridging sheet mutations also conferred increased susceptibility to the CXCR4
      ligand AMD-3100 in the context of the X4 tropic Env. However, these mutations had
      little effect on the rate of membrane fusion and little effect on susceptibility
      to enfuvirtide, a membrane fusion inhibitor whose activity is dependent in part
      on the rate of Env-mediated membrane fusion. Thus, mutations that reduce
      coreceptor binding and enhance susceptibility to coreceptor inhibitors can affect
      fusion and enfuvirtide susceptibility in an Env context-dependent manner.

PMID- 16631223
TI  - Stable integration of a functional shRNA expression cassette into the murine
      leukemia virus genome.
AB  - Short hairpin RNA (shRNA) can be stably expressed in cells to down-modulate gene
      expression. While retroviral and lentiviral vectors can be used to deliver
      shRNAs, the restricted viral titer is the major limitation for efficient gene
      transfer, which is especially important for cancer gene therapy. We were
      interested in using replicating murine leukemia virus (MLV) to enhance the shRNA
      transfer. Although stem loop structures could potentially interfere with the
      retroviral life cycle, we were able to demonstrate that the insertion of shRNA
      expression cassettes into MLV did not interfere significantly with viral fitness.
      The virus was genetically stable and able to silence target gene expression. Our
      results show that replicating MLVs are excellent tools for delivering shRNAs
      efficiently throughout the culture and have the potential to be used for gene
      function elucidation or even for cancer gene therapy.

PMID- 16631224
TI  - Vif-deficient HIV reverse transcription complexes (RTCs) are subject to
      structural changes and mutation of RTC-associated reverse transcription products.
AB  - Reverse transcription (RTn) in HIV-infected cells occurs in a nucleoprotein
      complex termed the reverse transcription complex (RTC). RTCs containing RT
      activity and integrase (IN) were shown to be heterogeneous in size and density on
      sucrose velocity and equilibrium gradients. WT and Vif-deficient (Deltavif) RTCs
      produced by infection with virus from permissive cells displayed similar
      sedimentation characteristics, while RTCs from Deltavif virus produced in non
      permissive cells demonstrated a reduction in the major RTC form and more of the
      RTn products in rapidly sedimenting structures. APOBEC3G derived from virions did
      not co-sediment with RTCs, but RTCs from Deltavif infections showed elevated
      levels of mutations in RTn products, consistent with APOBEC3G and other
      mutational mechanisms. The most mutated transcripts were present within rapidly
      sedimenting RTCs. Thus, virus without functional vif, produced from non
      permissive cells, forms abnormal RTCs that contain increased mutation of RTC
      associated RTn products in newly infected target cells.

PMID- 16631225
TI  - The catalytic properties of the recombinant reverse transcriptase of bovine
      immunodeficiency virus.
AB  - Bovine immunodeficiency virus (BIV) is a lentivirus with no proven pathogenesis
      in infected cattle. Yet, in experimentally infected rabbits, it causes an AIDS
      like disease. Consequently, we expressed two recombinant isoforms of BIV reverse
      transcriptase (RT), which differ in their C-termini, and studied their catalytic
      properties. Both isoforms prefer Mg(+2) over Mn(+2) with most DNA polymerase and
      ribonuclease-H substrates. The processivity of DNA synthesis by the BIV RTs is
      higher than that of HIV-1 RT, whereas the fidelity of synthesis is even lower
      than that of the HIV-1 enzyme. The ribonuclease-H cleavage pattern suggests that
      the spatial distance between the polymerase and ribonuclease-H active sites of
      the two BIV RT isoforms equals 20 nt, unlike the 17 nt distance observed in
      almost all other RTs. The longer BIV RT version is somewhat less active than the
      shorter version, suggesting that the extra 74 residues (with homology to
      dUTPases) might obstruct efficient catalysis.

PMID- 16631226
TI  - Endogenous processes during long-term starvation in activated sludge performing
      enhanced biological phosphorus removal.
AB  - In many biological wastewater treatment systems, bacterial growth and the amount
      of active biomass are limited by the availability of substrate. Under these low
      growth conditions, endogenous processes have a significant influence on the
      amount of active biomass and therefore, the overall system performance. In
      enhanced biological phosphorus removal (EBPR) systems endogenous processes can
      also influence the levels of the internal storage compounds of the polyphosphate
      accumulating organisms (PAO), directly affecting phosphorus removal performance.
      The purpose of this study was to evaluate the significance of different
      endogenous processes that occur during the long-term starvation of EBPR sludge
      under aerobic and anaerobic conditions. Activated sludge obtained from a
      laboratory sequencing batch reactor was used to perform a series of batch
      starvation experiments. Under aerobic starvation conditions we observed a
      significant decay of PAO (first-order decay rate of 0.15/d) together with a rapid
      utilization of polyhydroxyalkanoates (PHA) and a slower utilization of glycogen
      and polyphosphate to generate maintenance energy. On the other hand, anaerobic
      starvation was best described by maintenance processes that rapidly reduce the
      levels of polyphosphate and glycogen under starvation conditions while no
      significant decay of PAO was observed. The endogenous utilization of glycogen for
      maintenance purposes is currently not included in available EBPR models. Our
      experimental results suggest that mathematical models for in EBPR should
      differentiate between aerobic and anaerobic endogenous processes, as they
      influence active biomass and storage products differently.

PMID- 16631227
TI  - Nickel adsorption by magnetic alginate microcapsules containing an extractant.
AB  - The adsorption of heavy metals on biomaterials was investigated by studying the
      potential of alginate microcapsules containing an extractant (Cyanex 272) and
      magnetic nanoparticles (gamma-Fe2O3) for the adsorption of nickel (II) from
      aqueous solutions. A two-stage kinetics behaviour was observed with 70% of the
      maximum sorption capacity achieved within 8 h. An increase in nickel removal with
      increase in pH occurred, the maximum uptake capacity being around 0.42 mmol g-1
      at pH 8. The adsorption isotherm (pH about 5.3) was obtained in a wide range of
      initial nickel concentrations; the experimental data were fitted by a Langmuir
      model and the qmax value was estimated to be 0.52 mmol g-1. Moreover, including
      magnetic particles in the microcapsules allowed easy isolation of the beads from
      the aqueous solutions after the sorption process. Magnetic microcapsules are then
      suitable for the development of efficient biosorbents for removal and recovery of
      heavy metals from wastewater using magnetic separation.

PMID- 16631228
TI  - Factors affecting filtration characteristics in membrane-coupled moving bed
      biofilm reactor.
AB  - Factors affecting filtration characteristics in submerged hollow fiber membrane
      were investigated in membrane-coupled moving bed biofilm reactor (M-CMBBR). The
      trend of membrane biofouling in M-CMBBR was quite different from that in a
      conventional membrane bioreactor (MBR). The M-CMBBR showed much lower biofouling
      rate than a conventional MBR. Whereas the membrane biofouling in conventional MBR
      system is known to be dependent mostly on biochemical effects of mixed liquor
      (soluble COD, EPS, etc.), the extent of biofouling in M-CMBBR was largely
      dependent on the potential collision energy of biofilm carriers (media) moving
      freely and colliding with surfaces of submerged hollow fibers. The collisions
      between circulating media and hollow fiber membranes gave rise to frictional
      forces which mitigated the formation of biofilms on the outer surface of hollow
      fibers. Consequently, the membrane permeability was greatly enhanced. The
      potential collision energy of moving media was dependent on the media volume
      fraction as well as the air flow rate. The membrane permeability was found to be
      proportional to the relative potential collision energy of the biofilm carriers.
      The frictional effect on the morphology of biofilms formed on the surface of
      organic membrane under various operating condition was also examined and
      identified through their visualization with SEM and AFM.

PMID- 16631229
TI  - Degradation of macrolide antibiotics by ozone: a mechanistic case study with
      clarithromycin.
AB  - Macrolide antibiotics are widely used (in the order of 1g per person per year).
      They pass the body largely unchanged and are also not degraded in wastewater
      treatment plants. With not too much effort, they may be eliminated from their
      effluents by ozonation. The macrolide antibiotics have all a dimethylamino group
      at one of the carbohydrate residues in common. This functional group is the
      target of the ozone reaction, and clarithromycin has been selected here for a
      more detailed study. Since only the free amine reacts with ozone, the rate of
      reaction is pH dependent (at pH 7: k = 4 x 10(4) M(-1) s(-1)). In analogy to the
      ozonolysis of trimethylamine, the main reaction is a transfer of an O-atom
      yielding the N-oxide (identified by HPLC/MS-MS). A minor product (10%, based on
      formaldehyde yields) is demethylated clarithromycin (identified by HPLC/MS-MS).
      The dimethylamino group is thought to be essential for the binding of the
      macrolide antibiotics to their target. As a consequence, chemical changes of this
      functional group, notably the formation of the N-oxide that is no longer a proton
      acceptor, inactivates these drugs as assayed by the suppression of the growth of
      Pseudomonas putida. This is most important for wastewater treatment, as
      mineralization of clarithromycin by ozone would require 100 times as much ozone.

PMID- 16631230
TI  - Oxidative damage induced in hearts, kidneys and spleens of mice by landfill
      leachate.
AB  - The effects of the Xingou landfill leachate on levels of thiobarbituric acid
      reactive substances (TBARS) and the activities of Cu, Zn-superoxide dismutase
      (Cu, Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx) and catalase
      (CAT) were investigated in hearts, kidneys and spleens of Kunming albino mice of
      both sexes. Exposure to leachate caused significant increases of TBARS levels in
      the organs tested from mice of both sexes. For hearts, Cu, Zn-SOD, Se-dependent
      GPx and CAT activities were significantly increased at high concentrations for
      male mice, but the activities of these antioxidant enzymes were significantly
      increased at low concentration and decreased at high concentrations for female
      mice. For kidneys, Cu, Zn-SOD and Se-dependent GPx activities were significantly
      increased at high concentrations for male mice, but the activities were
      significantly increased at low concentrations and the ratio of increase was
      reduced with the increasing of concentration for female mice; CAT activities
      remained unchanged for male mice and were significantly increased at all
      concentrations tested for female mice. For spleens, Cu, Zn-SOD and Se-dependent
      GPx activities were significantly increased at high concentrations for male mice,
      but the activities were significantly increased at low concentrations and
      decreased at high concentrations for female mice; CAT activities remained
      unchanged for male mice and were significantly increased at high concentrations
      for female mice. The results suggest that leachate exposure can cause oxidative
      damage on hearts, kidneys and spleens of mice, and there were sex difference and
      organ difference in the response of antioxidant status.

PMID- 16631231
TI  - Identification and estrogenic characterization of impurities in commercial
      bisphenol A diglycidyl ether (BADGE).
AB  - A sample of commercial BADGE was fractioned by HPLC and eight impurities
      including novel propyl derivatives (2), (5) and (6) were identified by NMR
      spectrometry, FAB-MS and GC-MS. The estrogenicity, both agonist and antagonist,
      of fractions containing these impurities was measured with a yeast two-hybrid
      assay incorporating the human (hER alpha) and a competitive binding assay for hER
      alpha (ELISA). In the yeast two-hybrid assay, estrogenic antagonist activity was
      found in two fractions, while estrogenic agonist activity was not found in any.
      In the ELISA method, the binding affinity to hER alpha was found in three
      fractions. It is probable that a comprehensive assessment of the estrogenic
      properties of commercial BADGE, and their implications for human health, will
      require examination of all its components as described here.

PMID- 16631232
TI  - A comparative study on metal sorption by brown seaweed.
AB  - This study compared the sorption of Ag, Cd, Co, Cd, Mn, Ni, Pb and Zn by a Ca
      treated Sargassum biomass at pH 5.0, under low and high ionic strength (IS)
      conditions. The sorption isotherms of As [As(V)] and Cr [Cr(III) and Cr(VI)] were
      also determined at low IS. The isotherm data for the eight cationic metals and
      Cr(III) were well fitted by Langmuir equations. Generally, the maximum metal
      uptake (Umax) followed: Cr(III) > Pb approximately Cu > Ag approximately Zn
      approximately Cd > Ni approximately Mn approximately Co >> Cr(VI) >> As(V) at low
      IS and Pb > Cu > Co > Mn approximately Cd > Zn approximately Ag > Ni at high IS.
      As(V) did not bind to the seaweed at pH 5.0. The results indicated that sorption
      of Pb was not affected by the increasing IS, though the percentage of free Pb
      ions in the water was greatly reduced as predicted by the speciation model. High
      IS lowered Umax by 10-36% (except Co and Pb), and lowered the affinity constant
      of the metal by 33-91% for all cationic metals, as compared to low IS. Moreover,
      the removal efficiency of the cationic metals and Cr decreased exponentially with
      initial metal concentrations and was lower at high IS. Ion-exchange was the
      mechanism responsible for the cationic metal sorption onto the seaweed, and Na
      ion interfered with the cationic metal binding through electrostatic interaction.
      In conclusion, this study showed the differential binding capacity of the
      Sargassm biomass for different metals and oxidation states and the differential
      effects of IS. According to the present results, Sargassum may be considered a
      good biosorbent for cationic metals (especially Pb) in both low and high-salt
      containing wastewater.

PMID- 16631233
TI  - Mercury accumulation in grass and forb species as a function of atmospheric
      carbon dioxide concentrations and mercury exposures in air and soil.
AB  - The goal of this study was to investigate the potential for atmospheric Hg
      degrees uptake by grassland species as a function of different air and soil Hg
      exposures, and to specifically test how increasing atmospheric CO(2)
      concentrations may influence foliar Hg concentrations. Four common tallgrass
      prairie species were germinated and grown for 7 months in environmentally
      controlled chambers using two different atmospheric elemental mercury (Hg major;
      3.7+/-2.0 and 10.2+/-3.5 ng m(-3)), soil Hg (<0.01 and 0.15+/-0.08 micro g g(
      1)), and atmospheric carbon dioxide (CO(2)) (390+/-18, 598+/-22 micro mol mol(
      1)) exposures. Species used included two C4 grasses and two C3 forbs. Elevated
      CO(2) concentrations led to lower foliar Hg concentrations in plants exposed to
      low (i.e., ambient) air Hg degrees concentrations, but no CO(2) effect was
      apparent at higher air Hg degrees exposure. The observed CO(2) effect suggests
      that leaf Hg uptake might be controlled by leaf physiological processes such as
      stomatal conductance which is typically reduced under elevated CO(2). Foliar
      tissue exposed to elevated air Hg degrees concentrations had higher
      concentrations than those exposed to low air Hg degrees , but only when also
      exposed to elevated CO(2). The relationships for foliar Hg concentrations at
      different atmospheric CO(2) and Hg degrees exposures indicate that these species
      may have a limited capacity for Hg storage; at ambient CO(2) concentrations all
      Hg absorption sites in leaves may have been saturated while at elevated CO(2)
      when stomatal conductance was reduced saturation may have been reached only at
      higher concentrations of atmospheric Hg degrees . Foliar Hg concentrations were
      not correlated to soil Hg exposures, except for one of the four species
      (Rudbeckia hirta). Higher soil Hg concentrations resulted in high root Hg
      concentrations and considerably increased the percentage of total plant Hg
      allocated to roots. The large shifts in Hg allocation patterns-notably under soil
      conditions only slightly above natural background levels-indicate a potentially
      strong role of plants in belowground Hg transformation and cycling processes.

PMID- 16631234
TI  - Endometrial cancer in Kentucky: the impact of age, smoking status, and rural
      residence.
AB  - INTRODUCTION: The study objectives were to assess the effect of age, to evaluate
      the impact of smoking, and to determine the effect of rural residence on tumor
      characteristics, treatment modalities, and outcomes for Kentucky's endometrial
      cancer patients. METHODS: The Kentucky Cancer Registry identified Kentucky
      residents diagnosed with endometrial cancer from 1995 to 2002. Data abstracted
      included demographics, tumor characteristics, treatment, and recurrence/survival
      status. RESULTS: Three thousand five hundred and sixty-two women were diagnosed
      with endometrial cancer. Mean age at diagnosis decreased significantly (P=0.0388)
      over the 7-year period. Smokers had higher grade, stage, and worse outcomes.
      Rural women more often lacked commercial insurance, underwent less comprehensive
      surgical evaluation, and had less multimodality treatment. Increasing age
      (P<0.0001), positive or unknown smoking status (P=0.0003), black race (P<0.0001),
      no commercial insurance (P<0.0001), increasing grade or advanced stage
      (P<0.0001), small size of treating hospital (P<0.0001), and unknown nodal status
      (P<0.0001) were negatively associated with disease-specific survival. Lymph node
      sampling was performed in only 38.6% of women. On multivariate analysis, age (RR
      1.38 for 10 year increments; P<0.0001), smoking (RR 1.38; P=0.008), no commercial
      insurance or Medicaid (RR 1.87; P=0.0007), rural residence (RR 0.77; P=0.011),
      advanced stage and grade (RR 7.96, 3.96; P<0.0001), and no nodal evaluation or
      unknown nodal status (RR 2.32, 2.51; P<0.0001) significantly effected disease
      specific survival. CONCLUSIONS: Our data support a trend toward a younger age for
      endometrial cancer diagnosis, confirm the adverse impact of smoking and
      socioeconomic factors, and demonstrate an association between incomplete surgical
      staging and decreased survival.

PMID- 16631235
TI  - Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian
      cancer: an independent prognostic factor for tumor progression.
AB  - OBJECTIVES: Chemokine CXCL12 and its unique receptor CXCR4 have been recently
      implicated in cancer metastasis. Our goal was to explore expression of CXCL12 and
      CXCR4 protein in normal ovarian surface epithelium, primary tumors and paired
      metastases of epithelial ovarian cancer as well as its association with
      clinicopathological features. We also wanted to test if expression of CXCR4 has
      prognostic value in epithelial ovarian cancer patients. METHOD: Sections from 6
      normal ovarian surface epithelium, 44 primary epithelial ovarian tumors and 30
      paired metastatic tumors in omentum were evaluated for CXCL12 and CXCR4
      expression using immunohistochemistry (IHC). RESULTS: All samples of normal
      ovarian surface epithelium were negative for CXCL12 and CXCR4 protein. Ovarian
      cancer cells mainly showed cytoplasmic staining of CXCL12 and CXCR4. CXCL12 and
      CXCR4 staining were detected in 40/44 (91%) and 26/44 (59%) patients with primary
      epithelial ovarian tumors respectively. CXCR4 expression in primary tumors had no
      significant correlation with lymph nodes metastasis. However, if we combined
      CXCR4 expression in primary tumors with metastatic tumors, a significant
      correlation with lymph nodes metastasis was found (P = 0.018). The intensity of
      CXCL12 staining correlated with ascites (P = 0.014). The rate of CXCR4 expression
      in refractory and recurrent group (81% versus 28%, P = 0.0008) was significantly
      higher than that in no-recurrent group. After a median follow-up of 37 months,
      CXCR4 expression was found associated with an unfavorable prognosis with
      significantly reduced median disease progression-free survival and overall
      survival of 15 and 27 months (P = 0.0004, P = 0.017) respectively. Median time-to
      event was not reached in patients with negative CXCR4 staining. In multivariate
      analysis, CXCR4 expression and residual tumor size emerged as independent
      prognostic factors in epithelial ovarian cancer patients. CONCLUSIONS: This
      article provides the first evidence that CXCR4 expression could be an independent
      prognostic factor for epithelial ovarian cancer patients.

PMID- 16631236
TI  - Salvage cytoreductive surgery for recurrent endometrial cancer.
AB  - OBJECTIVE: To determine the survival impact of salvage cytoreductive surgery, and
      other prognostic variables, among patients with recurrent endometrial cancer.
      METHODS: All patients diagnosed with endometrial cancer recurrence between 7/1/97
      and 6/30/05 were retrospectively identified from the tumor registry database.
      Demographic, pathological, and clinical data were abstracted from the medical
      record. Survival estimates were calculated using the Kaplan and Meier method.
      Univariate and multivariate regression analyses were used to identify
      characteristics associated with overall survival from time of recurrence.
      RESULTS: Sixty-one patients were identified with endometrial cancer recurrence a
      median of 18.5 months after initial diagnosis. Median age at recurrence was 63
      years, and the median post-recurrence follow-up time was 22.0 months. Thirty-five
      patients underwent salvage cytoreductive surgery and had a median survival time
      of 28.0 months, compared to 13.0 months for patients treated non-surgically (P <
      0.0001). Complete cytoreduction (no gross residual) was achieved in 23/35
      surgical patients (65.7%). The median EBL was 350 cc and 28.6% of patients
      received blood products. There were no peri-operative deaths; however, 31.4% of
      patients experienced minor morbidity. Patients undergoing complete salvage
      cytoreduction had a median post-recurrence survival time of 39.0 months, compared
      to 13.5 months for those patients with gross residual disease (P = 0.0005). On
      multivariate analysis, salvage surgery and residual disease status were
      significant and independent predictors of post-recurrence survival. CONCLUSIONS:
      Complete salvage cytoreductive surgery for recurrent endometrial cancer is
      associated with prolonged post-recurrence survival compared to patients left with
      any gross residual disease. Additional studies are warranted to define
      appropriate surgical indications and selection criteria.

PMID- 16631237
TI  - Adjuvant radiotherapy in women with stage I endometrial cancer: a systematic
      review.
AB  - OBJECTIVE: To review the literature regarding the role of adjuvant radiotherapy
      (RT) in women with stage I endometrial cancer in terms of survival and pelvic
      control. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library
      databases was conducted for studies evaluating RT (1966 to October 2005).
      RESULTS: Five randomized trials were identified that evaluated adjuvant external
      beam radiotherapy (EBRT) and/or intracavitary radiotherapy (ICRT) including one
      in which women had undergone complete surgical staging. No survival differences
      were identified; however, none of the studies were powered enough to show a
      survival benefit. In three studies reporting subgroup analyses, intermediate-risk
      subgroups (stages IA and IB, grade 3 or stage IC) who received RT had fewer
      pelvic recurrences compared to women not receiving RT. Unfortunately, none of the
      studies reported ultimate pelvic control as an outcome. CONCLUSIONS: RT is not
      recommended in low-risk patients (stages IA, IB, grades 1 and 2). It is
      reasonable to consider EBRT for intermediate-risk subgroup patients (stage IC,
      grades 1 and 2, or stages IA, IB, grade 3), regardless of surgical staging, to
      reduce the risk of pelvic recurrence. EBRT is recommended for high-risk patients
      (stage IC, grade 3). The benefits of EBRT need to be weighed against the toxicity
      of treatment. Patients should be informed of the benefits and risks of EBRT.
      Additional analysis including ultimate pelvic control in subgroups would be
      helpful. More clinical trials are warranted to further define the role of EBRT in
      subgroups of patients and to clarify the role of ICRT.

PMID- 16631238
TI  - Patterns and frequency of recurrences of squamous cell carcinoma of the vulva.
AB  - OBJECTIVE: To analyze patterns and frequency of recurrences of squamous cell
      carcinoma (SCC) of the vulva after wide local excision (WLE) and superficial
      inguinal lymphadenectomy with separate incisions and to identify prognostic
      factors for the development of recurrences. METHODS: Between January 1985 and
      December 1999, all 125 consecutive patients with primary SCC of the vulva,
      treated with WLE and superficial inguinal lymphadenectomy, were retrospectively
      analyzed. Recurrences were registered by localization as: local, skin bridge,
      groin or distant. RESULTS: A local recurrence was diagnosed in 29 (23%) patients,
      11 (9%) developed a groin and 4 (3%) a distant recurrence. No skin bridge
      recurrences were identified. The 5 years local relapse-free survival was 70%.
      After a first local recurrence, 72% of these patients developed a second local
      recurrence. Adjusted for other predictors, older age (>74 years) is an
      independent risk factor for local recurrences (HR: 2.38; 95%-C.I.: 1.08-5.23) and
      stage III/IV cancer for developing groin/distant recurrences (HR: 3.03; 95%-C.I.:
      1.0-9.18). CONCLUSION: WLE and superficial inguinal lymphadenectomy with separate
      incisions result in a high groin recurrence rate in this study; superficial
      lymphadenectomy should be replaced by deep inguinofemoral lymphadenectomy. After
      a local recurrence, 72% of the patients developed a second local recurrence.
      These patients are at high risk and need a close follow-up.

PMID- 16631239
TI  - Endometrial carcinoma bone metastases in unusual sites.

PMID- 16631240
TI  - Palliative radiotherapy for recurrent granulosa cell tumor of the ovary: a report
      of 3 cases with radiological evidence of response.
AB  - BACKGROUND: The role of radiotherapy for recurrent or residual granulosa cell
      tumor of the ovary (GCTO) is controversial. One reason for this controversy may
      be that most published studies on this topic have not utilized sectional imaging
      to assess response to radiotherapy. We report on three cases of recurrent or
      residual GCTO that were treated with radiotherapy for which pre- and post
      treatment CT scans were available to assess response. CASE REPORTS: Case #1: A 77
      year-old woman with a 7 x 10-cm pelvic mass post-surgery was treated with
      radiotherapy to a dose of 45 Gy in 25 fractions followed by a boost of 10 Gy in 5
      fractions. Post-treatment scans revealed a decrease in tumor size to 4 x 2.5 cm.
      The reduction in tumor volume was 86%, and the duration of response was 13
      months. Case #2: A 73-year-old woman with multiple abdominal recurrences was
      treated with radiotherapy to a dose of 30 Gy in 20 fractions. The dominant mass
      shrank from 13 x 17 cm to 5.1 x 6.6 cm. The reduction in volume was 85%, and the
      duration of response has been 5 months. Her symptom of abdominal bloating and
      early satiety abated. Case #3: An 83-year-old woman with a 20 x 20 x 15-cm mass
      in the left abdomen was treated with radiotherapy to a dose of 45 Gy in 25
      fractions. The mass decreased in size to 3.7 x 2.5 cm post-treatment. The
      duration of response has been 21 months. Her symptom of left leg swelling
      disappeared after therapy. CONCLUSION: Radiotherapy is highly effective in
      treating recurrent or residual GCTO. In these three cases, the tumor volume
      decreased by 85 to 90%, and the duration of response has, up to now, been 5 to 21
      months.

PMID- 16631241
TI  - Gestational trophoblastic diseases: 2. Hyperglycosylated hCG as a reliable marker
      of active neoplasia.
AB  - OBJECTIVES: To determine whether circulating hyperglycosylated human chorionic
      gonadotropin (hCG-H), a promoter of choriocarcinoma growth and tumorigenesis, is
      a reliable marker of active gestational trophoblastic neoplasia (GTN) or
      choriocarcinoma, and whether hCG-H can consistently discriminate quiescent
      gestational trophoblastic disease (GTD) from neoplasia. METHODS: Patients were
      those referred to the USA hCG Reference Service for consultation. These included
      a total of 82 women with GTN, including 30 with histologic choriocarcinoma. They
      were compared with 26 patients with resolving hydatidiform mole and 69 with
      quiescent GTD (persistent positive low value of real hCG but no clinical evidence
      of disease). All were tested for total hCG and hCG-H. hCG-H was calculated as the
      percentage of total hCG (hCG-H(%)). RESULTS: We compared the utility of total hCG
      and hCG-H(%) in detecting active GTN and quiescent GTD. There was no significant
      difference when measuring total hCG (includes regular and hyperglycosylated hCG),
      between women with quiescent GTD and self-resolving hydatidiform mole compared to
      choriocarcinoma/GTN cases (P > 0.05 and P > 0.05). In contrast, hCG-H(%) was
      significantly higher in choriocarcinoma/GTN cases (P < 0.000001, and P <
      0.000001). The usefulness of hCG and hCG-H(%) testing was assessed for
      discriminating between the 69 quiescent GTD cases, which required no therapy, and
      choriocarcinoma/GTN which need treatment. While hCG would detect 62% and 24% of
      malignancies at a 5% false positive rate, hCG-H(%) would detect 100% and 84% of
      malignancies at this same false positive rate. Follow-up data were received and
      repeat consultations were performed in 23 cases in which active disease was
      subsequently demonstrated. In 12 of 23 cases, hCG-H(%) results were able to first
      identify active disease 0.5 to 11 months prior to rapidly rising hCG or detection
      of clinically active neoplasia. In the remaining 11 cases, hCG-H(%) active
      disease appeared at the same time as rising hCG or demonstrable clinical tumor.
      DISCUSSION AND CONCLUSION: hCG-H(%) appears to reliably identify active
      trophoblastic malignancy. It is a 100% sensitive marker for discriminating
      quiescent GTD from active GTN/choriocarcinoma. It is also a marker for the early
      detection of new or recurrent GTN/choriocarcinoma. The data presented appear
      sufficient to encourage the adoption of hCG-H as a tumor marker in trophoblastic
      disease. Further studies are now urgently required to confirm and extend our
      findings.

PMID- 16631243
TI  - Gestational trophoblastic diseases: 4. Presentation with persistent low positive
      human chorionic gonadotropin test results.
AB  - OBJECTIVES: A high proportion of women with persistent low levels of hCG, in the
      absence of pregnancy or any evidence of tumor, have received chemotherapy and
      hysterectomy for assumed malignancy. Such chemotherapy and surgery were
      ineffective and unwarranted. This study identifies the causes of persistent low
      level of hCG and provides guidelines for the management of these patients,
      preventing unnecessary treatment in the future. METHODS: The USA hCG Reference
      Service has consulted on 170 women with low levels of hCG persisting for 3 months
      or longer. Serum total hCG was measured in the Diagnostic Products Corporation
      (DPC) Immulite assay and hyperglycosylated hCG in the Nichols Advantage test.
      RESULTS: Among these 170 patients, the average persistent hCG result was 102 +/-
      152 mIU/ml, with a range of 6.1-900 mIU/ml. Thirteen (7.6%) of the 170 patients
      had true malignancy, 5 had placental site trophoblastic tumor, 3 had other
      gestational trophoblastic neoplasms (GTN), and 5 had non-trophoblastic
      malignancies. The remaining 157 patients had false-positive hCG, quiescent
      gestational trophoblastic disease (quiescent GTD), or pituitary hCG (hCG of
      pituitary origin). Of 71 patients with false-positive hCG, 47 patients received
      chemotherapy and 9 had surgery that had no effect on the level of hCG. Five of
      these patients with false-positive hCG were being monitored for hydatidiform mole
      or GTN. The majority of these cases were first investigated following an
      incidental pregnancy test. Of 69 patients who had quiescent GTD, 41 received
      chemotherapy and 9 underwent hysterectomy. All these therapies were unnecessary
      and ineffective. While 21 patients with quiescent GTD followed incidental
      pregnancy tests, the majority were discovered while monitoring patients after
      treatment for hydatidiform mole or GTN/choriocarcinoma (n = 48). Seventeen cases
      of pituitary hCG were found among those women who were peri- or post-menopause.
      Two patients also received chemotherapy for assumed malignancy which was not
      present. CONCLUSION: Clinicians frequently assume that an elevated hCG implies
      that a patient is pregnant or has GTD or recurrent GTN, even when apart from the
      pregnancy test, no clinical evidence was found to support such a diagnosis. In
      most of these cases of persistent low hCG etiologies, all therapies were found
      unnecessary and ineffective. Guidelines are proposed for managing these patients.
      It is essential to demonstrate a malignancy clinically and with readily available
      biochemical tests before initiating therapy. This applies whether the patient is
      identified by an incidental pregnancy test or is actively being monitored for
      gestational trophoblastic disease.

PMID- 16631244
TI  - The prognosis of gestational trophoblastic neoplasia patient with residual lung
      tumor after completing treatment.
AB  - OBJECTIVE: To analyze retrospectively the prognosis of gestational trophoblastic
      neoplasia (GTN) patients who achieved normal beta-hCG titer after completing
      treatment but remained with residual lung tumor. METHOD: A total of 1,130 GTN
      patients were hospitalized at Peking Union Medical College Hospital from January
      1985 to January 2004. Among these patients, 901 achieved complete remission (CR);
      152 achieved normal blood beta-hCG titer after the completion of treatment but
      remained with residual lung tumor (defined as partial remission). Retrospective
      analyses were carried out on the 152 patients. Statistical analysis was used to
      compare the recurrent rate of the CR patients with the progression rate of the
      152 patients. RESULT: 17 of the 152 patients lost follow-up. Of the rest 135
      patients followed up from 14 to 110 months, 83 showed no significant changes as
      to their residual tumors; 46 patients' residual tumors diminished or disappeared;
      and the other 6 patients got progression of disease (PD), with beta-hCG level
      going up 6-8 months after completing treatment. There is no significant
      statistical difference (P > 0.05) between the recurrent rate of the 901 CR
      patients and the progression rate of the 152 patients. There is also no
      significant statistical difference (P > 0.05) between the recurrent rate of the
      CR patients with lung metastasis and the progression rate of the 152 patients.
      CONCLUSION: After achieving normal beta-hCG titer, patients whose lung tumor
      stayed unchanged even following several additional courses of chemotherapy should
      be considered as CR patients. Follow-ups should be strictly carried out on these
      patients, especially at around 6 months after the completion of treatment, and
      particularly for high-risk and drug-resistant choriocarcinoma (CC) patients.

PMID- 16631245
TI  - Sequence dependence of hematologic toxicity using carboplatin and topotecan for
      primary therapy of advanced epithelial ovarian cancer: a phase I study of the
      Gynecologic Oncology Group.
AB  - PURPOSE: Selection of a feasible sequence and schedule of carboplatin in
      combination with topotecan for evaluation in advanced epithelial ovarian cancer
      (EOC). PATIENTS AND METHODS: Women with stages III-IV EOC or primary peritoneal
      carcinoma without prior chemotherapy were assigned to consecutive cohorts
      evaluating a "forward" (carboplatin day 1, topotecan days 1-3), "reverse"
      (carboplatin day 3, topotecan days 1-3), or "extended reverse" sequence
      (carboplatin day 5, topotecan days 1-5). Patients received 4 cycles carboplatin
      topotecan followed by 4 cycles carboplatin-paclitaxel. Feasibility was defined
      according to the cumulative proportion of patients with dose-limiting events
      (DLEs) during the first four cycles. RESULTS: Sixty-eight patients were enrolled
      across 5 cohorts. The forward sequence demonstrated unacceptable hematologic DLEs
      at the lowest topotecan dose (0.75 mg/m2/day x 3 days). The reverse sequence was
      feasible at 1.25 mg/m2/day x 3 days, with only 1/15 patients experiencing a DLE
      within 4 cycles, and 14/15 patients were able to receive 4 subsequent cycles of
      carboplatin-paclitaxel. The extended reverse sequence was associated with
      excessive DLEs at 1.00 mg/m2/day x 5 days. Prophylactic hematopoietic growth
      factors were not required. CONCLUSION: Higher doses of topotecan could be safely
      administered with reduced toxicity over multiple cycles using the reverse
      sequence, which was selected for phase III evaluation. The relative efficacy of
      the forward and reverse sequence is unknown.

PMID- 16631246
TI  - The effects of eticlopride and the selective D3-antagonist PNU 99194-A on food-
      and cocaine-maintained responding in rhesus monkeys.
AB  - The dopamine D3 receptor is mainly expressed in regions of the brain associated
      with the limbic system. D3 receptor blockade may antagonize cocaine reinforcement
      while producing less severe extrapyramidal side effects than blockade of D2
      receptors. The purpose of the present studies was to evaluate the effects of a
      selective D3 receptor antagonist and a non-selective D2/D3 receptor antagonist on
      food- and cocaine-maintained responding under two schedules of cocaine self
      administration. Adult male rhesus monkeys were trained to respond under multiple
      schedules of food (1.0 g pellets) and cocaine (0.01-0.3 mg/kg/injection)
      presentation. In one experiment (n=4), the schedule was a fixed-interval (FI) 3
      min and a second study (n=6) was conducted using a second-order fixed-ratio 5 (FI
      6-min:S) schedule. The D3 antagonist PNU 99194-A (0.3-3.0 mg/kg), which is 14
      fold selective for D3 relative to D2 receptors, or the D2/D3 antagonist
      eticlopride (0.001-0.03 mg/kg) was administered immediately prior to the
      experimental session for at least 5 consecutive sessions. Under the multiple FI 3
      min schedule of food and cocaine presentation, PNU 99194-A and eticlopride
      decreased food- and cocaine-maintained responding in a dose-dependent manner and
      irrespective of cocaine dose. Under the multiple second-order schedule of food
      and cocaine presentation, at least one dose of PNU 99194-A and eticlopride
      decreased cocaine- and food-maintained responding. These findings indicate that
      PNU 99194-A can decrease operant responding in monkeys, but not in a manner that
      would suggest selectivity of cocaine- over food-maintained responding. Future
      studies with more selective D3 antagonists are needed to better address the role
      of this receptor subtype in cocaine addiction.

PMID- 16631247
TI  - Cortisol responses to mental stress, exercise, and meals following caffeine
      intake in men and women.
AB  - Caffeine elevates cortisol secretion, and caffeine is often consumed in
      conjunction with exercise or mental stress. The interactions of caffeine and
      stress on cortisol secretion have not been explored adequately in women. We
      measured cortisol levels at eight times on days when healthy men and women
      consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic
      exercise protocols, followed by a midday meal, in a double blind, placebo
      controlled, crossover design. Men and women had similar cortisol levels at the
      predrug baselines, but they responded differently to mental stress and exercise.
      The cortisol response to mental stress was smaller in women than in men (p=.003).
      Caffeine acted in concert with mental stress to further increase cortisol levels
      (p=.011), the effect was similar in men and women. Exercise alone did not
      increase cortisol, but caffeine taken before exercise elevated cortisol in both
      men and women (ps<.05). After a postexercise meal, the women had a larger
      cortisol response than the men, and this effect was greater after caffeine
      (p<.01). Cortisol release in response to stress and caffeine therefore appears to
      be a function of the type of stressor and the sex of the subject. However,
      repeated caffeine doses increased cortisol levels across the test day without
      regard to the sex of the subject or type of stressor employed (p<.00001).
      Caffeine may elevate cortisol by stimulating the central nervous system in men
      but may interact with peripheral metabolic mechanisms in women.

PMID- 16631248
TI  - Soy consumption and mortality in Hong Kong: proxy-reported case-control study of
      all older adult deaths in 1998.
AB  - OBJECTIVES: This study investigates the relation between soy consumption and
      mortality in a population-based case-control study in Hong Kong of all adult
      deaths in 1998. METHODS: Multivariable logistic regression was used to assess the
      effect of soy on all-cause and cause-specific mortality in 21,494 deceased cases
      and 10,968 living controls who were ethnic Chinese aged 60 or above, using proxy
      reports collected from the person registering the death. Dietary habits were
      obtained from proxies in both cases and controls, based on a 7-item
      questionnaire. RESULTS: The adjusted odds ratios for all-cause mortality for soy
      consumption 4 or more times a week compared with less than once a month were 0.77
      (95% CI: 0.62, 0.95) for men and 0.66 (0.54, 0.81) for women. Mortality from lung
      cancer (males P = 0.02, females P = 0.02), colorectal cancer (males P = 0.07,
      females P < 0.001), stomach cancer (males P = 0.04, females P = 0.03), female
      breast cancer (P = 0.02) and ischemic heart disease (males P < 0.001, females P =
      0.002) was inversely associated with soy consumption. CONCLUSIONS: Our study
      suggests that maintaining traditional levels of soy consumption could be
      protective for some chronic diseases in China.

PMID- 16631249
TI  - Effect of egg yolk concentration on cryopreserving Spanish ibex (Capra pyrenaica)
      epididymal spermatozoa.
AB  - Tris-egg yolk based diluents provide adequate cryoprotection for the sperm of
      most wild species in which they have been tested. The objective of the current
      study was to evaluate various Tris-based diluents containing different
      concentrations of egg yolk, for the fertilizing ability of epididymal spermatozoa
      of the Spanish ibex (Capra pyrenaica) after freezing and thawing. For this
      purpose, we used heterologous in vivo fertilization by intrauterine insemination
      of domestic goats (Capra hircus). In Experiment 1, a Tris-citric acid-glucose
      (TCG) diluent containing 6% (v/v) egg yolk and a TCG extender containing 20% egg
      yolk were compared. In Experiment 2, a TCG-6% egg yolk extender was compared with
      Triladyl-20% egg yolk. Diluted samples were cooled slowly to 5 degrees C over 1 h
      and equilibrated at that temperature for 2 h. At that point, aliquots of samples
      were loaded into 0.25 ml straws, and frozen in nitrogen vapor for 10 min. The
      fertility of spermatozoa frozen in TCG-6% egg yolk was higher (P<0.05) than for
      those extended with TCG-20% egg yolk, and tended to be higher than for those
      frozen with Triladyl-20% egg yolk. From the results of this study, the use of
      Tris-based extenders containing low concentrations of egg yolk (6%) is
      recommended for cryopreserving Spanish ibex epididymal spermatozoa.

PMID- 16631250
TI  - Cytomegalovirus-associated hemophagocytic syndrome with clonal cytogenetic
      abnormalities in an elderly male.

PMID- 16631251
TI  - FLT3 inhibitor KRN383 on xenografted human leukemic cells harboring FLT3
      activating mutations FLT3 in AML: much more to learn about biology and optimal
      targeting.
AB  - Aberrant FLT3 function in leukemia blasts is associated with a poor prognosis. A
      number of FLT3 modulators are in development. FLT3 mutations may synergistize
      with other molecular abnormalities in myeloid transformation. Further insights
      into FLT3 biology are needed to optimally study the therapeutic role of FLT3
      inhibitors.

PMID- 16631252
TI  - Application of cattle manure as fertilizer in pastureland: estimating the
      incremental risk due to metal accumulation employing a multicompartment model.
AB  - Specific-site data of metal concentration in cattle manure from NW Spain and a
      multicompartment fate and exposure model were used to evaluate metal fate and the
      main routes of exposure after a 100 year period of application of cattle manure
      as fertiliser in pastureland. Risk assessment was performed as a probabilistic
      analysis, and using a conservative worst-case exposure scenario. An accumulation
      model was used to predict the metal concentration in each environmental medium of
      concern. The incremental risk was estimated for the population inhabiting the
      surroundings of the area by a general multiexposure model. Monte Carlo
      simulations were performed to analyse uncertainty of the results. Furthermore, a
      sensitivity analysis was carried out to identify the contribution to variance by
      the different metals and exposure routes. Among the five pathways evaluated, the
      ingestion of meat and milk from cattle grazing in the area represents the main
      contribution to total exposure. The results indicate that the incremental risk to
      human health for people living in the surroundings of pasturelands due to
      continuous application of cattle manure after a 100 year period are not
      negligible for the metals considered (Cd, Cu, Ni, Pb and Zn), posing a total
      Reasonable Maximum Exposure (RME) of 0.75, being the ingestion of meat the main
      exposure pathway.

PMID- 16631253
TI  - Giant secondary conjunctival inclusion cysts: a late complication of strabismus
      surgery.
AB  - PURPOSE: To present giant conjunctival inclusion cysts as a late complication of
      strabismus surgery. DESIGN: Retrospective case series of selected patients.
      PARTICIPANTS: Four patients with a history of strabismus surgery who had
      developed giant conjunctival inclusion cysts. METHODS: A chart review was
      performed. The patient's ocular history, ophthalmic examinations, and imaging
      (ultrasound/ultrasound biomicroscopy and/or computed tomography) were recorded.
      Surgical excision with subsequent histopathologic correlation was obtained in 3
      cases. MAIN OUTCOME MEASURES: Clinical and imaging characteristics with
      histopathologic correlation. RESULTS: Four patients with giant conjunctival
      inclusion cysts had a history of strabismus surgery. Ultrasound biomicroscopy was
      performed in 3 cases and revealed large, cystic, well-circumscribed tumors with
      low internal reflectivity and hyperechoic components. Computed tomography of the
      orbits was used to evaluate posterior extension. Their size induced limitation in
      motility, strabismus, and problems related to chronic exposure. Histopathologic
      evaluations were consistent with benign inclusion cysts of the conjunctiva.
      CONCLUSIONS: Giant conjunctival inclusion cysts may appear decades after
      strabismus surgery. Tumor size, cystic nature, and involvement of underlying
      structures can be determined by ultrasonography and radiographic imaging.
      Complete surgical removal can be curative.

PMID- 16631254
TI  - Anterior chamber depth measurement before and after photorefractive keratectomy:
      comparison between IOL master and Orbscan II.
AB  - PURPOSE: To measure the anterior chamber depth (ACD) with 2 different devices
      before and after photorefractive keratectomy (PRK). DESIGN: Noncomparative case
      series. PARTICIPANTS: One hundred forty-three eyes of 143 patients who had
      undergone PRK with refractive errors ranging from -13.13 diopters (D) to +7 D
      (mean, -3.67+/-3.58) were analyzed. METHODS: The ACD values preoperatively and at
      1, 3, and 6 months postoperatively were measured with the Orbscan II and IOL
      Master. The results were analyzed using the Pearson correlation. MAIN OUTCOME
      MEASURE: Anterior chamber depth. RESULTS: The instruments showed good agreement
      between the measurements before and after surgery. A significant decrease between
      the preoperative and 1-month postoperative measurements was found in the ACD
      measured from the epithelium with Orbscan II (P<0.01) and IOL Master (P<0.01). A
      nonsignificant decrease with both IOL Master (P>0.01) and Orbscan II (P>0.01) was
      found between 3 and 6 months after surgery. The ACD measured from the endothelium
      using the Orbscan II showed a significant difference only between the 3- and 6
      month follow-up data (P<0.01). CONCLUSIONS: The 2 devices showed good agreement,
      and the changes detected postoperatively seem to be related not only to corneal
      thinning but also to anterior segment remodeling.

PMID- 16631255
TI  - Late-onset retinoblastoma in a well-functioning fellow eye.
AB  - PURPOSE: To describe the documented growth, clinical course, and histopathology
      of retinoblastomas in an untreated and otherwise normal right eye of a 27-year
      old white male with a g.153211T>A (p.Tyr606X) mutation in the retinoblastoma 1
      gene, whose left eye was enucleated at age 2 years for 2 retinoblastomas. DESIGN
      AND PARTICIPANTS: Retrospective interventional case report. INTERVENTIONS: Over
      the years, the right eye was irradiated twice and underwent trans-pars plana
      vitrectomy, transscleral cryocoagulation, argon laser photocoagulation of tumors
      and their feeder vessels, extracapsular cataract extraction with posterior
      chamber lens implantation, and neodymium:yttrium-aluminum-garnet laser treatment
      of after-cataract in the form of Elschnig's pearls. Finally, the patient received
      combination chemotherapy with etoposide, methotrexate, actinomycin D, cisplatin,
      and vincristine. RESULTS: The eye finally had to be removed 12 years later due to
      tumor recurrences and seeding, pseudohypopyon, and elevated intraocular pressure.
      Histopathology showed microcellular retinoblastoma cells in the anterior chamber
      angle and trabecular meshwork without subconjunctival extension and in the nasal
      ciliary body, pars plana, internal limiting membrane, and optic nerve head
      anterior to the cribriform plate. The patient is without local or systemic
      recurrences at age 50, 11 years after the last eye was enucleated. CONCLUSIONS:
      This report shows that retinoblastoma patients may have tumor growth in their
      fellow eye 25 years after the first eye and also that Elschnig's after-cataract
      pearls still can arise after irradiation of a lens with 45 Gy.

PMID- 16631256
TI  - Patterns of memory impairment in bipolar disorder and unipolar major depression.
AB  - Unipolar and bipolar depression are known to exert detrimental effects on
      learning and memory processes. However, few comparisons have been undertaken
      between bipolar and unipolar patients with comparable illness histories, and
      predictors of impairment are not well understood. Adult outpatients with unipolar
      major depressive illness (UP, n = 30) and bipolar disorder (BP, n = 30), group
      matched for illness duration and severity of depressive symptomatology (16%
      clinically remitted, 42% partially remitted, 42% depressed), and 30
      demographically matched controls completed measures of general cognitive
      functioning and declarative memory. Despite comparable general intellectual
      abilities, BP and UP patients exhibited significant memory deficits relative to
      healthy controls. A similar deficit profile was observed in both patient groups,
      involving poorer verbal recall and recognition. Impairments were not secondary to
      strategic processing deficits or rapid forgetting. Although depression severity
      was not associated with neurocognitive performance, number of hospitalizations
      and family history of mood disorder significantly affected memory function in BP,
      but not UP, patients. Results suggest qualitatively similar patterns of memory
      impairment in BP and UP patients, consistent with a primary encoding deficit.
      These impairments do not appear to be secondary to clinical state, but rather
      suggest a similar underlying pathophysiology involving medial temporal
      dysfunction.

PMID- 16631257
TI  - Hyperactivity of the hypothalamic-pituitary-adrenal axis and mortality in major
      depressive disorder.
AB  - Convergent evidence indicates that HPA-axis hyperactivity is a risk factor for
      suicide in major depressive disorder, and seven independent reports have shown
      that patients with abnormal dexamethasone suppression test (DST) results have
      significantly higher rates of eventual suicide. The identification of
      interactions between DST results and other clinical predictors would enhance risk
      assessment, but modest sample sizes have limited such analyses in earlier
      cohorts. Subjects with major depressive disorder who participated in research
      protocols at the University of Michigan between 1980 and 1991, who had fully
      structured diagnostic interviews, and who underwent a 1-mg DST while actively
      depressed were screened with the National Death Index for a mean (S.D.) follow-up
      period of 18.0 (5.5) years. Of 334 subjects, 69 (20.7%) were identified as having
      died. Of these, 13 (18.8%) had died by suicide and 32 (46.4%) from cardiovascular
      causes. Baseline DST results did not significantly predict death from suicide or
      from cardiovascular disease for the sample as a whole. Significant relationships
      between DST results and later suicide did exist for inpatients, for patients with
      manifest suicidality and, in particular, for inpatients with manifest
      suicidality. Because nearly all previous reports of DST results and suicide
      described depressed inpatients, it is possible that the DST is a useful predictor
      only within this population.

PMID- 16631258
TI  - A generalized bias against disconfirmatory evidence in schizophrenia.
AB  - Fixation onto false/unrealistic beliefs is a core feature of schizophrenic
      delusions. A recent study conducted by our research group has provided evidence
      for the presence of a bias against disconfirmatory evidence (BADE) in patients
      with schizophrenia. Importantly, this bias was found with delusion-neutral
      material. To further validate a BADE as an underlying component of schizophrenic
      delusions, we recruited 34 presently deluded and non-deluded patients with
      schizophrenia, along with 26 healthy and 46 mixed psychiatric control
      participants. Participants were administered a closure task. On each trial, a
      common object (e.g., elephant) was increasingly disambiguated (i.e., shown in
      decreasing degrees of fragmentation). The participants were required to assess
      the plausibility of different interpretations at each of the up to eight stages
      in each trial. In line with the main hypothesis, patients with schizophrenia
      downgraded the ratings for incorrect interpretations significantly less over the
      course of task completion than did healthy and psychiatric controls. In contrast,
      the gradual upgrading of correct interpretations was similar across all groups,
      suggesting that the pattern of results obtained for incorrect interpretations
      reflects a BADE and not a mere repetition of prior responses or a lack of
      attention to the task at hand. The present study suggests that a BADE is a core
      feature of schizophrenia, and that this style of thinking is not confined to
      delusion-congruent scenarios.

PMID- 16631259
TI  - CD24 Ala/Val polymorphism and multiple sclerosis.
AB  - CD24 is expressed on a broad range of cells in the immune and central nervous
      systems and appears to be required for development of experimental autoimmune
      encephalomyelitis in mice. Association of a CD24 Ala/Val coding polymorphism with
      susceptibility to and progression of multiple sclerosis was recently reported. We
      typed this coding polymorphism in a combined cohort of 1,180 cases and 1,168
      unrelated and family-based controls from Belgium and the UK, but were unable to
      confirm either association. Since the CD24 gene is part of a segmental
      duplication, special care is required for the identification and genotyping of
      single nucleotide polymorphisms.

PMID- 16631260
TI  - Microarray analysis of IFN-gamma response genes in astrocytes.
AB  - IFN-gamma (IFN-gamma) has been shown to activate astrocytes to acquire immune
      functions. In this study the effect of IFN-gamma on murine astrocytes was
      investigated via microarray analysis. The activating effect of IFN-gamma on the
      astrocyte transcriptome showed predominance toward pathways involved in adaptive
      immunity, initiation of the immune response and innate immunity. Previously
      unknown astrocytic genes expressed included members of the p47 GTPases and
      guanine nucleotide binding protein (GBP) families. Down-regulatory effects of IFN
      gamma stimulation were confined to pathways involved in growth regulation, cell
      differentiation and cell adhesion. This data supports the notion that astrocytes
      are an important immunocompetant cell in the brain and indicate that astrocytes
      may have a significant role in various infectious diseases such as Toxoplasmic
      Encephalitis and neurological diseases with an immunological component such as
      Alzheimer's and autoimmune disorders.

PMID- 16631261
TI  - Social stress alters the severity and onset of the chronic phase of Theiler's
      virus infection.
AB  - Social stress alters the acute phase of Theiler's virus infection (TMEV), a model
      of multiple sclerosis. Stress applied prior to infection had deleterious disease
      outcomes, while stress applied concurrent with infection was protective. The
      current study examined multiple behavioral (motor impairment, open field
      activity) and immunological measures (IL-6, antibodies to virus and myelin
      proteins) in both the acute and chronic phases of TMEV. It was found that stress
      applied prior to infection exacerbated disease outcomes, while concurrent
      application was protective in both disease phases.

PMID- 16631262
TI  - Glucagon-like peptide-1 receptor and proglucagon expression in mouse skin.
AB  - Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone expressed by
      alternative post-translational processing of proglucagon in the intestines,
      endocrine pancreas, and brain. The multiple antidiabetogenic actions of GLP-1
      include stimulation of the proliferation and differentiation of the insulin
      producing beta cells in the pancreas. The GLP-1 receptor is widely distributed
      and has been identified in the endocrine pancreas, intestinal tract, brain, lung,
      kidney, and heart. Here we report the expression of the GLP-1 receptor and
      proglucagon in the skin of newborn mice located predominantly in the hair
      follicles, as well as in cultures of skin-derived cells that also express nestin,
      a marker of cultured cells that have dedifferentiated by epithelial to
      mesenchymal transition. In cultured skin cells, GLP-1 activates the MAPK/ERK
      signal transduction pathway, associated with cellular proliferation,
      differentiation, and cytoprotection. No evidence was found for the activation of
      cAMP or Ca2+ signaling pathways. Further, redifferentiation of cultured skin
      derived cells by incubation in differentiation medium containing GLP-1 induced
      expression of the proinsulin-derived peptide, C-peptide. These findings suggest a
      possible paracrine/autocrine role for GLP-1 and its receptor in skin development
      and possibly also in folliculogenesis.

PMID- 16631263
TI  - Optimization of RNA isolation from the archaebacterium Methanosarcina barkeri and
      validation for oligonucleotide microarray analysis.
AB  - The recent completion of a draft genome sequence for Methanosarcina barkeri has
      allowed the application of various high throughput post-genomics technologies,
      such as nucleic acid microarrays and mass spectrometry of proteins to detect
      global changes in transcription and translation that occur in response to
      experimental treatments. However, due to the production of a thick
      heteropolysaccharide outer layer, M. barkeri usually grows in large aggregates of
      cells rather than as individual, planktonic cells. Complete disruption of these
      aggregates and lysis of the released cells presents technical difficulties in
      ensuring the isolation of intact RNA from the entire population of cells. Initial
      attempts at isolating RNA from M. barkeri using several standard extraction
      protocols gave incomplete lysis of cells and resulted in low yields of poor
      quality RNA. In this study, we tested several chemical and mechanical disruption
      modifications of standard RNA extraction methods to optimize the extraction
      efficiency and minimize the number of unlysed cells remaining after extraction.
      As a further test of the quality of the resulting RNAs, their performance in
      replicate microarray analyses were determined. The results showed that inclusion
      of a liquid nitrogen grinding step prior to Trizol extraction, combined with
      moderate bead beating, yielded the most complete cell lysis, the highest yield of
      RNA and the most reproducible microarray results for M. barkeri. From these
      results it is clear that the methods used to isolate RNA can have a significant
      impact on the variability, trend and, presumably, the accuracy of microarray
      data. In addition, functional analysis of the microarray results obtained with
      RNA from the optimized protocol showed that, as expected, the genes involved in
      methanogenesis were among the most highly expressed genes in M. barkeri.

PMID- 16631264
TI  - Rapid test for distinguishing membrane-active antibacterial agents.
AB  - In the search for antibacterial agents with a novel mode-of-action (MOA) many
      targeted cellular and cell-free assays are developed and used to screen chemical
      and natural product libraries. Frequently, hits identified by the primary screens
      include compounds with nonspecific activities that can affect the integrity and
      function of bacterial membrane. For a rapid dereplication of membrane-active
      compounds, a simple method was established using a commercially available
      Live/Dead(R) Bacterial Viability Kit. This method utilized two fluorescent
      nucleic acid stains, SYTO9 (stains all cells green) and propidium iodide (stains
      cells with damaged membrane red) for the drug-treated bacterial cells. The cells
      were then either examined visually by fluorescence microscopy or their
      fluorescence emissions were recorded using a multi-label plate reader set to
      measure emissions at two different wavelengths. The ratio of green versus red was
      compared to a standard curve indicating the percentage of live versus dead
      bacteria. Nine known antibiotics and 14 lead compounds from various antibacterial
      screens were tested with results consistent with their MOA.

PMID- 16631265
TI  - Detection of Clavibacter michiganensis subsp. michiganensis in tomato seeds using
      immunomagnetic separation.
AB  - The use of pathogen-free plant material is the main strategy for controlling
      bacterial canker of tomato caused by Clavibacter michiganensis subsp.
      michiganensis. However, detection and isolation of this pathogen from seeds
      before field or greenhouse cultivation is difficult when the bacterium is at low
      concentration and associated microbiota are present. Immunomagnetic separation
      (IMS), based on the use of immunomagnetic beads (IMBs) coated with specific
      antibodies, was used to capture C. michiganensis subsp. michiganensis cells,
      allowing removal of non-target bacteria from samples before plating on non
      selective medium. Different concentrations of IMBs and of two antisera were
      tested, showing that IMS with 10(6)IMBs/ml coated with a polyclonal antiserum at
      1/3200 dilution recovered more than 50% of target cells from initial inocula of
      10(3) to 10(0)CFU/ml. Threshold detection was lower than 10CFU/ml even in seed
      extracts containing seed debris and high populations of non-target bacteria. The
      IMS permitted C. michiganensis subsp. michiganensis isolation from naturally
      infected seeds with higher sensitivity and faster than direct isolation on the
      semiselective medium currently used and could become a simple viable system for
      routinely testing tomato seed lots in phytosanitary diagnostic laboratories.

PMID- 16631266
TI  - Scientific and regulatory considerations on the immunogenicity of biologics.
AB  - Immune responses against non-vaccine biologics can affect their efficacy and
      safety, resulting in adverse events that could include administration reactions,
      hypersensitivity, deficiency syndromes and lack of a clinical response in treated
      patients. With the relatively recent development of numerous biologics,
      immunogenicity testing has become a key component in the demonstration of
      clinical safety and efficacy; in fact, it is highly unlikely that regulatory
      approval would be granted for a biologic without an assessment of its
      immunogenicity. However, recommendations from regulatory agencies regarding the
      requirements for when and how to carry out immunogenicity testing are dispersed
      among numerous guidance documents. To enable the evaluation of the effects of
      immunogenicity on safety and efficacy, the authors have consolidated
      recommendations from the regulatory guidelines, and present current approaches
      and future directions for the assessment of immunogenicity.

PMID- 16631267
TI  - The role of whole pelvic radiotherapy in locally advanced prostate cancer.
AB  - Routine PSA testing has led to diagnosis and treatment of prostate cancer at
      earlier stages than previously. Earlier and technically-improved treatment,
      together with escalation of dose has enhanced cure rates. Although, the incidence
      of nodal metastases is now lower than in pre-PSA days, more extended pelvic
      lymphadenectomies have shown the actual rate of lymph node involvement to be
      higher than had been determined from standard radical prostate surgery. As in
      cancers in other sites, especially in their earlier stages, lymph node metastases
      may exist in the absence of haematogenous dissemination. This, together with the
      improved rates of control of the primary prostate tumour, suggests that elective
      irradiation of early-stage lymph nodes from prostate cancer should enhance
      survival in a manner analogous to improvements seen with this approach in other
      cancers. Although, the absolute incidence of positive nodes in locally advanced
      prostate cancer warrants elective radiotherapy, it is relatively low and the
      modest improvements to be expected may be undetected in the results of a small
      trial.

PMID- 16631268
TI  - Treatment of squamous cell anal canal carcinoma (SCACC) with pulsed dose rate
      brachytherapy: a retrospective study.
AB  - BACKGROUND AND PURPOSE: To evaluate the results of pulsed dose rate brachytherapy
      (PDR) in SCACC. MATERIAL AND METHODS: From 1996 to 2002, 71 patients (pts) with
      SCACC were treated with PDR brachytherapy. The median age was 61.2 years (35-88),
      with a sex ratio of 1 M/6.5 F. The TNM classification was: 14 T1, 41 T2, 15 T3
      and 1 T4, 52 N0, 13 N1, 3 N2 and 3 N3. All the pts were M0. Treatment started
      with external beam irradiation to the posterior pelvis (mean dose: 45.5 Gy).
      Forty-seven patients received chemotherapy (neoadjuvant/concomitant or both).
      After an interval of 2-6 weeks, PDR interstitial brachytherapy was performed. The
      mean dose was 17.8 Gy to the 85% reference isodose of the Paris system. RESULTS:
      Treatment was interrupted in only one pt. With a median follow-up of 28.5 months,
      2-year actuarial overall survival was 90%. Fourteen relapses occurred (four
      distant, three regional, and seven local). Ten patients developed a grade III
      complication (Lent Soma scale) and two a grade IV complication (colostomy or
      abdominal perineal resection for necrosis). CONCLUSION: PDR appears to be an
      effective treatment for SCACC. It is capable of reproducing the results usually
      observed with continuous LDR.

PMID- 16631269
TI  - Neural correlates of Chinese word-appropriateness judgment: an MEG study.
AB  - To study the neural correlates of Chinese word-appropriateness judgment, we used
      2-word phrases and corresponding meaningless pairs produced by replacing the
      second words (W2) with homophones. Fourteen right-handed healthy adults viewed
      word pairs randomly presented one word at a time, and judged the lexical
      appropriateness of the W2 for combining its preceding first word (W1) into a
      meaningful phrase. We measured magnetoencephalographic (MEG) responses to W1,
      appropriate W2, and inappropriate W2 stimuli. For each subject, multi-dipole
      analyses revealed sequential neuromagnetic activations which involved the
      bilateral visual cortices at approximately 100 milliseconds (ms), the bilateral
      occipitotemporal regions at approximately 190 ms, and the left temporal lobe at
      approximately 350 ms (M350) following stimuli. We found that the word
      appropriateness had no clear effect on the occipitotemporal activation to W2
      stimuli, whereas the M350 activation to inappropriate W2 was greater than that to
      W1 or appropriate W2. In 8 of our subjects, we found an additional activation in
      the right temporal region, with a smaller amplitude as compared with the left
      M350. Our results suggest that the M350 activity reflects both lexical and
      semantic appropriateness assessment. The lateralized M350 strengths may be used
      to determine the language dominance hemisphere; and additionally, our 2-word
      contexture judgment paradigm can be applied in further research on the cortical
      processing of lexicon-semantic information in Chinese speakers.

PMID- 16631270
TI  - Effect of size and charge on pharmacokinetics and in vivo MRI contrast
      enhancement of biodegradable polydisulfide Gd(III) complexes.
AB  - The purpose of this study is to investigate how the structures of polydisulfide
      Gd(III) complexes affect their pharmacokinetics and in vivo contrast enhancement
      as biodegradable macromolecular MRI contrast agents. A negatively charged
      polydisulfide Gd(III) complex, (Gd-DTPA)-cystine copolymers (GDCP), and a neutral
      agent, (Gd-DTPA)-cystine diethyl ester copolymers (GDCEP), with different
      molecular weights were prepared and characterized. The MRI contrast enhancement
      of the agents was studied in mice. Neutral GDCEP showed more rapid degradation
      than negatively charged GDCP in the blood plasma. Consequently, GDCP resulted in
      more significant and prolonged contrast enhancement in the blood pool and liver
      than GDCEP. The size of GDCEP did not significantly affect its in vivo contrast
      enhancement due to rapid degradation and clearance from the blood circulation.
      The increase in the molecular weight of GDCP resulted in prolonged in vivo
      contrast enhancement in the blood pool. The structural modification of
      polydisulfide Gd(III) complexes resulted in biodegradable macromolecular MRI
      contrast agents with different degradability and in vivo contrast enhancement.

PMID- 16631271
TI  - Characterization of insulin protection properties of complexation hydrogels in
      gastric and intestinal enzyme fluids.
AB  - The objective of this study was to elucidate the mechanisms contributing to oral
      bioavailability of insulin by poly(methacrylic acid grafted with poly(ethylene
      glycol)) (P(MAA-g-EG)) hydrogels using the gastric and intestinal fluids from
      rats. P(MAA-g-EG) hydrogels successfully protected the incorporated insulin from
      enzymatic degradation by forming interpolymer complexes in the gastric fluid. The
      hydrogels also showed the insulin protection ability by itself. In the intestinal
      fluid, P(MAA-g-EG) hydrogels significantly decreased the insulin degradation rate
      and calcium ion levels, while protein levels was not changed. Insulin protecting
      effects were dependent on the fraction of the carboxylic group in the polymer
      networks. Moreover, the insulin degradation inhibitory effect was significantly
      correlated with Ca2+ deprivation ability of P(MAA-g-EG) hydrogels in the
      intestinal fluid, implying that the Ca2+ deprivation ability plays an important
      role in the inhibition of the intestinal enzyme activities. Insulin-loaded P(MAA
      g-EG) (ILPs) hydrogels showed a rapid and almost complete insulin release even in
      the presence of intestinal proteases. These results suggested that the insulin
      protection ability of the hydrogels contributed to improve oral insulin
      absorption and that P(MAA-g-EG) hydrogels can be an excellent carrier for
      protecting insulin during their transit through the GI tract.

PMID- 16631272
TI  - Prolonged blood concentration of prednisolone after intravenous injection of
      liposomal palmitoyl prednisolone.
AB  - We compared the pharmacokinetic behavior of drugs after an intravenous
      administration of prednisolone (PLS), palmitoyl prednisolone (Pal-PLS), and
      liposomal Pal-PLS in rats. Pal-PLS showed higher lipophilicity and higher binding
      to plasma protein than PLS, and PLS regeneration in rat blood and liver
      homogenates. After the intravenous administration of Pal-PLS solution in
      polyethylene glycol (PEG) 400 to rats, Pal-PLS disappeared from the blood in a
      two-phase mode and PLS was rapidly regenerated. Pal-PLS showed a significantly
      higher accumulation than PLS in the liver and lung. The administration of Pal-PLS
      incorporated into egg yolk phosphatidylcholine (EggPC)/cholesterol (Chol)
      liposomes enhanced Pal-PLS concentrations in the blood, liver, and lung compared
      to that of Pal-PLS solution in PEG 400, suggesting the rapid removal of liposomes
      by the mononuclear phagocytic system. Pal-PLS incorporated into PEGylated
      liposomes constituted with EggPC/Chol/1% L-alpha
      distearoylphosphatidylethanolamine (DSPE)-PEG 2000 and EggPC/Chol/10% DSPE-PEG
      2000 decreased the initial distribution of Pal-PLS, and successfully maintained
      the blood concentrations of Pal-PLS and PLS. Thus, we could change the
      pharmacokinetics of PLS by introducing the palmitoyl function into the molecule
      and its liposomal formulation including PEGylation. This is the first study to
      evaluate liposomal PLS constituted with a lipophilic derivative and PEG lipids.

PMID- 16631273
TI  - Automatic postural responses in individuals with peripheral neuropathy and ankle
      foot orthoses.
AB  - Eleven individuals with sensory neuropathy participated in static and dynamic
      balance tests with and without ankle-foot orthoses (AFOs). During the tests the
      subjects were required to stand on a fixed or moving computer-controlled platform
      with their eyes open or closed. Equilibrium scores, response latency, and
      strength scores were obtained. For all tests equilibrium scores were
      significantly larger in experiments with AFOs in comparison to conditions without
      AFOs (P<0.01). Decreased latency of responses with AFOs were recorded for medium
      and large magnitudes of movements of the platform in forward and backward
      directions. In addition, increased strength scores were observed when AFOs were
      used. The results indicate that AFOs could contribute significantly to postural
      control in individuals with peripheral neuropathy by providing auxiliary sensory
      cues to intact tissues of the lower extremities. These results have clinical
      implications that primarily aid in the understanding of how individuals with
      peripheral neuropathy benefit from the use of AFOs for postural stability.

PMID- 16631274
TI  - Association of gliclazide and left ventricular mass in type 2 diabetic patients.
AB  - Diabetes is a state of increased oxidant stress and there is evidence that
      oxidation may play a role in the genesis of higher left ventricular mass.
      Gliclazide has been shown to possess free radical scavenging properties. We
      assessed whether gliclazide may have a beneficial effect on left ventricular mass
      via reducing 8-iso-prostaglandin F(2alpha) concentrations, a reliable marker of
      oxidant injury. A total of 41 patients were randomized into two groups. All
      patients had been taking glibenclamide for more than 3 months before being
      randomized to switch either an equipotent dose of gliclazide (n=21) or to
      continue on glibenclamide (n=20). Baseline characteristics were similar in both
      groups. At 6 months, gliclazide-treated patients showed a significant regression
      in left ventricular mass index compared with the glibenclamide-treated group (
      16% versus 3%, P=0.003). Gliclazide patients had significantly lower plasma 8-iso
      prostaglandin F(2alpha) compared with baseline (299+/-101 pg/ml versus 400+/-112
      pg/ml, P=0.001) and the glibenclamide-treated patients (299+/-101 pg/ml versus
      388+/-114 pg/ml, P=0.01) after 6-month therapy. The magnitude of left ventricular
      mass index regression correlated univariately with the magnitude of inhibition of
      8-iso-prostaglandin F(2alpha) formation (r=0.74, P<0.0001). Multivariate analysis
      revealed that regression of left ventricular mass index significantly correlated
      with the changes of 8-iso-prostaglandin F(2alpha) (P<0.0001, adjusted R(2)=0.55).
      Our findings demonstrated for the first time that in addition to its primary
      hypoglycemia, gliclazide may have an additional effect on reducing left
      ventricular mass, possibly through attenuation of free radical formation.

PMID- 16631275
TI  - Increased oxidative stress is associated with decreased circulating levels of
      adiponectin in Japanese metabolically obese, normal-weight men with normal
      glucose tolerance.
AB  - To investigate the relationship between oxidative stress and circulating levels
      of adiponectin in Japanese metabolically obese, normal-weight [MONW; BMI<25 and
      visceral fat area; VFA > or =100 cm2 by abdominal computed tomography (CT)
      scanning] men with normal glucose tolerance (NGT), we measured the plasma levels
      of free 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and adiponectin in 28 MONW
      and 23 normal men. The plasma levels of free 8-epi-PGF2alpha were measured using
      a commercially available enzyme immunoassay (EIA) kit (Cayman Chemical, Ann
      Arbor, MI). The plasma levels of adiponectin were measured using a
      radioimmunoassay kit (LINCO Research, St. Charles, MO). Plasma levels of 8-epi
      PGF2alpha in MONW subjects (30.4+/-4.0 pg/ml; P<0.01) were significantly
      increased compared to controls (8.1+/-1.3 pg/ml). The plasma levels of
      adiponectin were significantly decreased in MONW subjects (8.6+/-0.9 microg/ml;
      P<0.01) as compared to normal subjects (11.6+/-0.6 microg/ml). The plasma levels
      of 8-epi-PGF2alpha and adiponectin were significantly correlated in MONW (r=
      0.617, P<0.01) and in all (MONW+normal) (r=-0.620, P<0.01) subjects. The plasma
      levels of 8-epi-PGF2alpha and adiponectin were significantly correlated after
      adjustment for VFA in MONW subjects (F=11.042, P<0.01). The present study showed
      that systemic increase in oxidative stress correlates with decreased circulating
      levels of adiponectin in Japanese MONW men with NGT. Although correlation does
      not prove causation, this observation suggests that increased oxidative stress
      may decrease the production of adiponectin in Japanese MONW men with NGT.

PMID- 16631276
TI  - Dynamic nucleosomes and gene transcription.
AB  - Gene transcription occurs on a nucleosomal template known as chromatin. The
      recruitment of the transcriptional regulators and the transcription machinery to
      promoter chromatin is coordinated by a genetic code on the DNA and an epigenetic
      code on the histone proteins. Chromatin is not a stable environment; rather, the
      histones, the transcription regulatory proteins and the enzymes that modify and
      mobilise nucleosomes are in a dynamic state. Thus, at any one time, the factors
      associated with a region will cooperate or compete to change the rate of inter
      conversion between permissive and non-permissive chromatin states, leading to
      activation or repression of transcription. Here, new concepts such as dynamic
      nucleosomes and a dynamic histone code in gene transcription are explored.

PMID- 16631277
TI  - Drug delivery in degenerative joint disease: where we are and where to go?
AB  - Drug discovery and delivery to retard the degeneration of joint tissues are
      challenging. Current treatment is generally inadequate. This commentary places in
      perspective the inadequacy characteristic of existing therapeutics and the
      promising developments embodied in the newer therapeutics administered via the
      oral or intra-auricular routes.

PMID- 16631278
TI  - 'The weight of a thought': food-related thought suppression in obese and normal
      weight youngsters.
AB  - OBJECTIVE: The ironic processing theory by Wegner states that suppressing
      unwanted thoughts can be counterproductive because it leads to a rebound of these
      thoughts, eventually causing increased preoccupations. In line with this view,
      the present study examines the effects of suppressing food- and eating- related
      thoughts in obese and non-obese youngsters. METHOD: Ninety-seven clinically obese
      and non-obese boys and girls, with different levels of dietary restraint, were
      asked to monitor their thoughts about food for 5min, during three subsequent
      trial periods. Participants were instructed to suppress thoughts about food or to
      merely monitor them. The number of food-related thoughts was recorded across
      trials. RESULTS: No indication was found for an overall post-suppression rebound
      effect. However, when examining subgroups of high and low restrained eaters,
      results showed that the obese high restrained eaters displayed a pattern that was
      indicative of a rebound effect for food-related thoughts. None of the other
      groups shared these effects. DISCUSSION: The results corroborate the hypothesis
      that trying not to think about food and eating may be counterproductive, at least
      for a subgroup of clinically obese high restrained eaters. Thought suppression
      may be one of the factors contributing to acceleration and perpetuation of
      burdensome food-related thinking in clinically obese high restrained eaters.

PMID- 16631279
TI  - [Thalidomide in adult multisystem Langerhans cell histiocytosis: a case report].
AB  - BACKGROUND: Adult multisystem Langerhans cell histiocytosis is an excepted
      disorder, which have several treatments. The purpose of this study was to test
      the disease-controlling effect of thalidomide in a case of adult multisystem
      Langerhans cell histiocytosis with cutaneomucous and hypothalamic localizations
      at dermatology department, of Mohammed-V military hospital, Rabat. CASE REPORT: A
      43-year-old women, presented multifocal chronic Langerhans cell histiocytosis
      confined to cutaneous, oral cavity, perianal, mastoid and hypothalamic areas,
      with severe disabling ulcers in intertriginous areas, diabetes insipid and
      amenorrhoea. We treated with thalidomide 200 mg/day after neurological
      examination. A rapid initial response with total diminution of the involved skin
      area, and diminution of diabetes insipid. She remained in remission for 1 year.
      No adverse effects from treatment were observed at clinical and
      electrophysiological examinations. CONCLUSION: Thalidomide treatment is an
      adequate therapeutic measure in adult Langerhans cell histiocytosis, which is
      rare and difficult to treat. Our case showed the efficacy of thalidomide at
      cutaneomucosal and hypothalamic manifestations.

PMID- 16631280
TI  - [Mutation of protein kinase JAK2 in polycythemia vera: new perspectives in
      physiopathology and therapy].
AB  - INTRODUCTION: The pathogenic mechanisms of polyvythemia vera (PV) still remain
      unknown, although there is evidence that genetic parameters may play a role in
      the pathogenesis of the disease. EXEGESIS: In 2005, many international research
      groups have identified an acquired mutation in the Janus kinase (JAK2) gene of
      chromosome 9; the mutation is defined by a valine-to-phenylalanine substitution
      at amino acid position 617 (V617F) in the JAK2's pseudokinase domain. JAK2 V617F
      mutation has been found in as high as 65 to 97% of patients with PV. Both in
      vitro and in vivo functional studies have further indicated that JAK2 V617F
      mutation leads to dysregulation of kinase activity, explaining, in part, clinical
      and biochemical features of PV. CONCLUSION: These data suggest that JAK2 V617F
      mutation may be a novel diagnostic marker of PV. Moreover, JAK2 V617F mutation
      finding may permit promising therapeutic approaches in patients with PV,
      particularly tyrosine kinase inhibitors; preliminary series have, in fact,
      underscored the potential efficacy of imatinib mesylate in PV.

PMID- 16631281
TI  - The effects of a reminiscence education program on baccalaureate nursing
      students' cultural self-efficacy in caring for elders.
AB  - The increase in our minority elder population has created a need to develop
      innovative programs that prepares students who are competent in gerontological
      nursing skills and sensitive to cultural differences. The purpose of this pilot
      study was to test the effects of a reminiscence education program on BSN
      students' cultural self-efficacy in caring for elders. An interrupted time series
      design with a nonequivalent, no-treatment control group was used with 64 nursing
      students recruited from a northeast university in the United States. The
      intervention consisted of a two-hour reminiscence education program and a 13 week
      period in which the experimental group implemented integrative reminiscence with
      elders during their community health practicum. The eldercare cultural self
      efficacy scale was the outcome measure. Results indicated that students receiving
      the reminiscence education program demonstrated significantly higher levels of
      eldercare cultural self-efficacy F(1, 62)=5.34, p=0.024 than those not receiving
      the intervention. Reminiscence education programs implemented as part of clinical
      practicums may assist to increase nursing students' perceptions of confidence in
      caring for elders. Implications for nursing education and the care of diverse
      elders are discussed.

PMID- 16631282
TI  - Surgical patient education: Turkish nursing students experiences.
AB  - Patient education has been widely used by medical schools and schools of nursing
      as a method for evaluating clinical performance. Training of patients provides a
      viable method for teaching and evaluating nurse practitioner students as they
      progress through their educational programs toward clinical competency.
      Evaluation of patient education experience provided objective and valid
      information regarding the students' delivery of didactic information and ability
      to apply knowledge in the clinical setting. The purpose of this article is to
      describe the preparation of materials for preoperative patient education and to
      evaluate patient education carried out by second-year students of the University
      Of Ege School Of Nursing. In this study, students, patients and lecturers
      evaluated patient education carried out by the nursing students. Criteria
      including relationships between people (listening, talking and communication
      ability), and behavior before education (prepare topic content, develop
      appropriate material for the topic, communicate which topic will be explained,
      etc.) and during education (attract listeners' attention to the topic, give
      information about the target, present the content and material of the subject
      well, etc.) were appraised. According to the results of evaluation, the education
      carried out by the students achieved the highest score from patients; the
      students gave the second-highest score. The lecturers gave scores that were lower
      than those of students and patients. At the end of this study, it has been found
      that patients were pleased with the education prepared according to their
      individual requirements and the students were pleased with giving education with
      the material they have prepared employing their own creativity.

PMID- 16631283
TI  - Relationships among body weight, joint moments generated during functional
      activities, and hip bone mass in older adults.
AB  - OBJECTIVE: To investigate the relationships among hip joint moments produced
      during functional activities and hip bone mass in sedentary older adults.
      METHODS: Eight male and eight female older adults (70-85 yr) performed functional
      activities including walking, chair sit-stand-sit, and stair stepping at a self
      selected pace while instrumented for biomechanical analysis. Bone mass at
      proximal femur, femoral neck, and greater trochanter were measured by dual-energy
      X-ray absorptiometry. Three-dimensional hip moments were obtained using a six
      camera motion analysis system, force platforms, and inverse dynamics techniques.
      Pearson's correlation coefficients were employed to assess the relationships
      among hip bone mass, height, weight, age, and joint moments. Stepwise regression
      analyses were performed to determine the factors that significantly predicted
      bone mass using all significant variables identified in the correlation analysis.
      FINDINGS: Hip bone mass was not significantly correlated with moments during
      activities in men. Conversely, in women bone mass at all sites were significantly
      correlated with weight, moments generated with stepping, and moments generated
      with walking (p<0.05 to p<0.001). Regression analysis results further indicated
      that the overall moments during stepping independently predicted up to 93% of the
      variability in bone mass at femoral neck and proximal femur; whereas weight
      independently predicted up to 92% of the variability in bone mass at greater
      trochanter. INTERPRETATION: Submaximal loading events produced during functional
      activities were highly correlated with hip bone mass in sedentary older women,
      but not men. The findings may ultimately be used to modify exercise prescription
      for the preservation of bone mass.

PMID- 16631284
TI  - Metals leachability from medical waste incinerator fly ash: A case study on
      particle size comparison.
AB  - This paper presents the results from a study of metals leachability of medical
      waste incinerator fly ash in Japan on the basis of particle size. Sequential
      extraction and Toxicity Characteristic Leaching Procedure (TCLP) analysis were
      carried out in order to quantify the leaching amount of metals in each
      categorized particle size. Sequential extraction was also subjected to identify
      the preference of binding matrix of metals. The results of sequential extraction
      showed an increase both exchangeable and carbonate associated chromium
      concentrations in the bigger particle size fractions. Likewise, concentrations of
      carbonate matrix of arsenic and tin tended to increase in the bigger particle
      size fractions. In contrast, exchangeable associated cadmium as well as both
      exchangeable and carbonate matrices of barium were found higher in the smaller
      particle size fractions. However, no correlation was found in Kendal-tau
      correlation analysis between particle size of the ash and metals leachability of
      the TCLP.

PMID- 16631285
TI  - Continental scale passive air sampling of persistent organic pollutants using
      rapidly equilibrating thin films (POGs).
AB  - A novel design of rapidly equilibrating passive air sampler was deployed at 38
      sites across 19 European countries to investigate short-term spatial variability
      of persistent organic pollutants (POPs). Devices were sealed in airtight
      containers to eliminate the possibility of contamination during transit and
      couriered to recipients with deployment instructions. Exposure times of 7days
      permitted the use of back trajectory analysis to further understand the factors
      responsible for influencing the large-scale spatial distribution of PCBs, PBDEs,
      PCNs, PAHs, lindane and HCB. Following sampler harvest, devices were sealed and
      returned for analysis. Comparison of sequestered levels showed that PAHs
      exhibited the greatest spatial variability (by a factor of 30) with higher levels
      often associated with greater population density. In contrast, HCB values were
      much more uniform, reflecting its well mixed distribution in the atmosphere.
      Spatial variation was strongly influenced by air mass origin, with lower levels
      being observed at most sites impacted by maritime air masses.

PMID- 16631286
TI  - Metal accumulation in wild plants surrounding mining wastes.
AB  - Four sites were selected for collection of plants growing on polluted soil
      developed on tailings from Ag, Au, and Zn mines at the Zacatecas state in Mexico.
      Trace element concentrations varied between sites, the most polluted area was at
      El Bote mine near to Zacatecas city. The ranges of total concentration in soil
      were as follows: Cd 11-47, Ni 19-26, Pb 232-695, Mn 1132-2400, Cu 134-186 and Zn
      116-827 mg kg(-1) air-dried soil weight. All soil samples had concentrations
      above typical values for non-polluted soils from the same soil types (Cd 0.6+/
      0.3, Ni 52+/-4, Pb 41+/-3mg kg(-1)). However, for the majority of samples the
      DTPA-extractable element concentrations were less than 10% of the total. Some of
      the wild plants are potentially metal tolerant, because they were able to grow in
      highly polluted substrates. Plant metal analysis revealed that most species did
      not translocate metals to their aerial parts, therefore they behave as excluder
      plants. Polygonum aviculare accumulated Zn (9236 mg kg(-1)) at concentrations
      near to the criteria for hyperaccumulator plants. Jatropha dioica also
      accumulated high Zn (6249 mg kg(-1)) concentrations.

PMID- 16631287
TI  - Evaluation of performance reference compounds in polyethylene-based passive air
      samplers.
AB  - Polyethylene-based passive air samplers (PSDs) were loaded with performance
      reference compounds (PRCs) and deployed in a wind tunnel to examine the effects
      of wind speed on sampler performance. PRCs could be loaded reproducibly into
      PSDs, with coefficients of variation only exceeding 20% for the more volatile
      compounds. When PSDs were exposed to low (0.5-1.5 m s-1) and high (3.5-4.5 m s-1)
      wind speeds, PRC loss rate constants generally increased with increasing wind
      speed and decreased with increasing sampler/air partition coefficients. PSD-based
      air concentrations calculated using PRC loss rate constants and sampler/air
      partition coefficients and air concentrations measured using active samplers
      compared closely. PRCs can be used to account for the effect of differences in
      wind speeds on sampler performance and measure air concentrations with reasonable
      accuracy.

PMID- 16631288
TI  - An integrated numerical and physical modeling system for an enhanced in situ
      bioremediation process.
AB  - Groundwater contamination due to releases of petroleum products is a major
      environmental concern in many urban districts and industrial zones. Over the past
      years, a few studies were undertaken to address in situ bioremediation processes
      coupled with contaminant transport in two- or three-dimensional domains. However,
      they were concentrated on natural attenuation processes for petroleum
      contaminants or enhanced in situ bioremediation processes in laboratory columns.
      In this study, an integrated numerical and physical modeling system is developed
      for simulating an enhanced in situ biodegradation (EISB) process coupled with
      three-dimensional multiphase multicomponent flow and transport simulation in a
      multi-dimensional pilot-scale physical model. The designed pilot-scale physical
      model is effective in tackling natural attenuation and EISB processes for site
      remediation. The simulation results demonstrate that the developed system is
      effective in modeling the EISB process, and can thus be used for investigating
      the effects of various uncertainties.

PMID- 16631289
TI  - Seasonal and spatial patterns of metals at a restored copper mine site II. Copper
      in riparian soils and Bromus carinatus shoots.
AB  - Soil and plants were sampled throughout winter and spring near a perennial stream
      traversing a restored mine site in a winter-rainy climate. Within 1m of an acidic
      reach of the stream, soil had pH 3-5 and 50-100 microg/g "bioavailable" copper
      (extractable with 0.01 M CaCl2). Soil 2-3 m from the stream had pH 5-8 and lower
      (less than 3 microg/g) bioavailable copper. "Oxide-bound" copper (extractable
      with 2N HCl) was 50-100 microg/g at most locations. Copper concentrations in the
      shoots of field-collected Bromus carinatus declined from 20 microg/g in winter to
      2 microg/g in spring at all sampling sites. A similar temporal pattern was found
      in plants grown under controlled conditions. Thus B. carinatus has a
      developmental program for control of shoot copper concentration, causing a
      seasonally-varying pattern of copper phytoaccumulation over a large range of
      copper availability in the soil.

PMID- 16631290
TI  - Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer.
AB  - Codeine is metabolized by the cytochrome P450 2D6 (CYP2D6) to morphine. Codeine
      is a much weaker agonist at mu opioid receptors than morphine. Therefore, codeine
      analgesia is highly dependent on CYP2D6 activity. Large prospective studies in
      the clinical environment do not exist, but it appears reasonable to avoid codeine
      use in CYP2D6 poor metabolizers (PMs). CYP2D6 metabolizes other opioid
      analgesics, including tramadol, dihydrocodeine, oxycodone and hydrocodone,
      although they have been less systematically studied. It is unclear whether these
      other pro-drugs may be as completely dependent on CYP2D6 for their analgesia as
      codeine. We describe a patient identified as a CYP2D6 PM with a history of
      problems with opioid analgesics. The patient was an 85-year-old female Caucasian
      who had hip surgery. The patient had a long-standing intolerance to codeine. In
      her first admission, she couldn't tolerate the regimen of oxycodone combined with
      tramadol prns (as needed). She was genotyped as a CYP2D6 PM and after the
      information was provided to the treating physician in her second admission, she
      seemed to have a better response to hydrocodone. Large case-control naturalistic
      studies followed by randomized trials in patients taking opioid analgesics may be
      needed to definitively establish that CYP2D6 genotyping has clinical relevance in
      the use of several opioid analgesics.

PMID- 16631291
TI  - Repetitive transcranial magnetic stimulation (rTMS) in a patient suffering from
      comorbid depression and panic disorder following a myocardial infarction.
AB  - Application of repetitive transcranial magnetic stimulation was effective and
      safe in treating a 55-year-old man with comorbid depression and panic disorder,
      which occurred 6 months after a myocardial infarction.

PMID- 16631292
TI  - Involvement of histamine receptors in the acquisition of inhibitory avoidance in
      Carassius auratus.
AB  - This study investigated the involvement of H(1) and H(2) histaminegic receptors
      on the acquisition of a new task in Carassius auratus by using an inhibitory
      avoidance paradigm in which the animals had to learn to avoid an aversive
      stimulus. Before training, the fish received injections of H(2) antagonist
      zolantidine at a dose of 20 mg/kg, or H(1) antagonist chlorpheniramine at a dose
      of 4 or 16 mg/kg. Control animals were injected with distilled water. A
      facilitatory effect of chlorpheniramine was observed at the dose of 16 mg/kg. On
      the other hand, the administration of 20 mg/kg of zolantidine inhibited
      acquisition. Place preference conditioning was used to observe the aversive or
      reinforcing effects of the drugs, which could interfere with the inhibitory
      avoidance procedure; however, no effects were observed. Thus, it can be suggested
      that both receptors, H(1) and H(2), are involved in the acquisition of a new task
      in this species.

PMID- 16631293
TI  - Evidence of astrogliosis in rat hippocampus after d-amphetamine exposure.
AB  - INTRODUCTION: Psychostimulants such as amphetamine (AMPH) induce manic-like
      symptoms in humans and studies have suggested that bipolar disorder (BD) may be
      associated to dopamine dysfunction. Glial fibrillary acidic protein (GFAP) up
      regulation is considered a marker of astrogliosis, and it has been associated to
      behavioral sensitization. PURPOSE: We aimed to investigate the behavioral effects
      of acute and chronic AMPH on rat locomotion and assess GFAP levels in rat cortex
      and hippocampus. METHODS: Rats were administered either acute (single dose) or
      chronic (seven days) d-amphetamine IP injection. Locomotion was assessed with an
      open-field test and GFAP immunoquantity was measured using ELISA. RESULTS:
      Chronic, but not acute, administration of AMPH increased GFAP levels in rat
      hippocampus. No differences were observed in rat cortex. CONCLUSIONS: Repeated
      exposure to AMPH leads to an astroglial response in the hippocampus of rats.

PMID- 16631294
TI  - Adjunctive risperidone, olanzapine and quetiapine for the treatment of
      hospitalized patients with bipolar I disorder: a retrospective study.
AB  - This study evaluated the overall effectiveness and tolerability of atypical
      antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment
      of bipolar inpatients. After screening 463 patients, the medical records of 158
      inpatients with bipolar I disorder, who were given olanzapine, risperidone or
      quetiapine as adjuncts to mood stabilizers for at least 1 month and not
      administered with any other antipsychotics, were examined. Details of the
      tolerability and effectiveness were reviewed according to the treatment records
      during their hospital stay. The results showed equivalent effectiveness based on
      the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF)
      score between the three atypical antipsychotics. The frequency of the
      extrapyramidal symptom-related side effects were higher in the risperidone
      treated group than in the olanzapine and quetiapine-treated group. This suggests
      that risperidone, olanzapine and quetiapine have a comparable effectiveness in
      inpatients with bipolar I disorder in a naturalistic setting. However, there were
      some differences in tolerability between these results as reported from previous
      Western studies.

PMID- 16631295
TI  - Prolongation of clozapine-induced leukopenia with olanzapine treatment.
AB  - Clozapine is a well-known antipsychotic to cause fatal agranulocytosis but there
      are only a few case reports about the risk of leukopenia and agranulocytosis
      associated with other atypical antipsychotics. Olanzapine has structural
      pharmacological similarities to those of clozapine and reports about
      haematological adverse effects of olanzapine include three groups: the first
      group includes cases of olanzapine-induced neutropenia, the second informing that
      olanzapine is safe after clozapine induced agranulocytosis and the third group
      forms prolongation of clozapine-induced leukopenia with olanzapine use. The aim
      of this paper is to report a case of prolongation of clozapine-induced leukopenia
      despite olanzapine treatment and discuss leukopenia caused by atypical
      antipsychotic use in the light of recent and limited literature.

PMID- 16631296
TI  - Monotherapy with reboxetine in amphetamine withdrawal syndrome.
AB  - Amphetamine withdrawal can induce a condition with the symptoms of major
      depression. We report the case of a 46-year-old woman with antecedents of abuse
      of amphetamines and amphetamine derivatives from age 16 to age 41, who in the 5
      years since withdrawal presented recurrent depression resistant to treatment. She
      was treated with maximum doses of selective serotonin reuptake inhibitors and
      lithium, but there was no remission of symptoms. On being treated with
      reboxetine, a selective noradrenaline reuptake inhibitor, euthymia was achieved,
      without negative after effects. Several studies have shown that noradrenaline
      plays an important role in the modulation of the response to amphetamines. The
      findings in this case suggest that reboxetine may constitute an interesting
      alternative for the treatment of amphetamine withdrawal syndrome (AWS).

PMID- 16631297
TI  - The toxic effects of 4-tert-octylphenol on the reproductive system of male rats.
AB  - The aim of the present study is to investigate the toxic effect of 4-tert
      octylphenol (OP) on testicular functions of rats. Male Sprague-Dawley rats were
      orally administered different doses of OP at the levels of 0 (control), 50, 150
      and 450 mg/kg/d for 30 d. Testicular functions were assessed by histopathology,
      testicular sperm head counts, daily sperm production, sperm motility (measured by
      computer assisted sperm analysis, CASA) and biochemical indices (marker
      testicular enzymes). The size and weight of the testis, epididymis, and prostate
      were reduced in all the three dosages. Histopathologically, damages of
      spermatogenic cells and Sertoli cells were observed by electron microscope.
      Testicular sperm numbers, daily sperm production and activity of alkaline
      phosphatase (ALP) were decreased significantly in the 450 mg/kg/d OP group. The
      motility of spermatozoa was reduced significantly in 150 and 450 mg/kg/d treated
      groups. These data demonstrate that OP affects testicular functions. The primary
      sites of action may be spermatogenic cells and Sertoli cells. The results of the
      present study provide first information of OP on sperm motility.

PMID- 16631298
TI  - [National survey of the deep vein thrombosis in plastic and aesthetic surgery,
      consequences and guidelines].
AB  - This first French national survey of the deep vein thrombosis and embolism risk
      during plastic and aesthetic surgery shows the reality of this complication.
      Eighty percent of the french plastic surgeons had deep vein thrombosis in their
      patients and 53% had pulmonary embolism. There are no guidelines in our
      speciality in French. The author reviews the bibliography and guidelines of all
      the other societies around the world as experts' recommendations during the
      national congress of the French Plastic Reconstructrice and Aesthetic Surgery
      (SOF.CPRE) in 2004.

PMID- 16631299
TI  - [Subperiosteal midface lifting].
AB  - Since 1990, when we had found the solutions about the oval of the face and the
      neck problems by the vertical lift, our whole attention was focused on the
      midface. We have been through the "cheek lift", high SMAS incision. We followed
      Oscar Ramirez and Richard Anderson in the subperiosteal undermining of the mid
      face under endoscopic control by a buccal and temporal incision. The actual
      technic made possible by Paul Tessier's work who initiated the subperiosteal
      undermining and Oscar Ramirez who initiated the endoscopy. The endoscopy allowed
      us to go through this technic, but now we don't use it anymore. We have to credit
      Thierry Besins who mixed these concepts alltogether to obtain a complete and
      effective technic. The idea is to move up the centrofacial structures and to
      secure them reliably because of the perioste strengh. This technic solve in an
      unparallel way, all the stigmata of the centrofacial aging; so, we have a
      scarless lifting. For the one who have a neck problem, we associate the deep
      vertical lift.

PMID- 16631300
TI  - Reaching the public via a multi media campaign as a first step to nationwide
      public access defibrillation.
AB  - Public access defibrillation (PAD) is a promising strategy to fight sudden
      cardiac death. The Austrian Red Cross provided automated external defibrillators
      (AEDs) and basic life support (BLS) training as an "all inclusive package"
      combined with on site consultation and maintenance with annual retraining as a
      part of a nationwide PAD programme. A multi media campaign was started to promote
      the package and to increase awareness about sudden cardiac death. Data about the
      campaign, its recognition by the public in Austria and the number of packages
      were recorded. Sixty-eight percent of the Austrian public above the age of 15
      years were able to recall the multi media campaign. Comparing the periods before
      and after the campaign, the number of website hits climbed significantly from
      2,931 hits/month (1,866-6,168) to 4,812 hits/month (3,432-13,434) (p=0.0276). The
      number of AED services implemented before the campaign increased significantly
      (p=0.0026) in the time after the campaign. Therefore, we conclude that a multi
      media campaign is useful to stimulate public discussion and it encourages
      companies to buy "all inclusive packages" containing AEDs, BLS training, on site
      consultation and maintenance. These measures represent a possible first step in
      introducing PAD but it seems that they have to be continued on a constant basis.

PMID- 16631301
TI  - Topological and dynamical properties of Azurin anchored to a gold substrate as
      investigated by molecular dynamics simulation.
AB  - A classical molecular dynamics study of the electron transfer protein azurin,
      covalently bound to a gold substrate through its native disulphide group, is
      carried out at full hydration. With the aim of investigating the effects on the
      protein structure and dynamics as induced by the presence of an electric field,
      simulations are performed on neutral, positively and negatively charged
      substrates. A number of parameters, such as the average structure, the root mean
      square deviations and fluctuations, the intraprotein hydrogen bonds and solvent
      accessible surface of the protein, are monitored during 10 ns of run. The
      orientation, the height and the lateral size of the protein, with respect to the
      substrate are evaluated and compared with the experimental data obtained by
      scanning probe nanoscopies. The electron transfer properties between the copper
      redox center and the disulphide bridge bound to the substrate are investigated
      and briefly discussed.

PMID- 16631302
TI  - On the relationship between set-out rates and participation ratios as a tool for
      enhancement of kerbside household waste recycling.
AB  - Although the use of kerbside recycling facilities by householders is often key to
      the reduction of materials disposed of to landfill, the quantitative assessment
      of householders' recycling behaviour is problematic. This study introduces a
      method to diagnose recycling behaviour by assessing kerbside scheme use in terms
      of the set-out of recyclate containers compared to the proportion of households
      participating in recycling (participation ratio). Application of numerical
      behaviour models demonstrated that kerbside recycling in sampled regions of the
      UK tends to be consistent with householders using kerbside schemes more
      frequently than would be observed with random patterns of use that are uniform
      amongst all householders. When aggregated to collection rounds, householders'
      modal recycling behaviour tended towards either non-participation or frequent
      participation. We propose that initiatives to enhance kerbside recycling should
      employ such quantitative assessments of recycling behavioural modes to inform and
      guide promotional and educational strategies. A conceptual model for prioritizing
      campaigns to promote recycling at the kerbside on the basis of identifiable and
      quantifiable patterns of householder recycling behaviour is presented.

PMID- 16631303
TI  - High incidence of prostate cancer detected by saturation biopsy after previous
      negative biopsy series.
AB  - OBJECTIVES: We explored the yield of saturation biopsy and developed a nomogram
      predicting the probability of prostate cancer (PCa) on the basis of saturation
      biopsy. MATERIALS AND METHODS: Between 2001 and 2004, saturation biopsies
      (average of 24 cores) were performed in 161 men with persistently elevated
      prostate specific antigen (PSA) level (median, 9 ng/ml). All had at least two
      previously negative, eight-core biopsy sessions. PCa predictors on saturation
      biopsy were integrated within multivariate nomograms. RESULTS: PCa detection was
      41% (n=66 of 161). PSA density and transition zone volume were the most
      significant predictors of PCa on saturation biopsy. The accuracy of the nomogram
      with the best performance characteristics was 72%. CONCLUSIONS: Saturation biopsy
      may be indicated in men with a persistent suspicion of PCa. High-risk individuals
      can be identified accurately with our nomogram.

PMID- 16631304
TI  - Intraoperative frozen section analysis to monitor nerve-sparing radical
      prostatectomy.

PMID- 16631305
TI  - Removal of copper(II) and lead(II) from aqueous solution by manganese oxide
      coated sand II. Equilibrium study and competitive adsorption.
AB  - The adsorption equilibrium of MOCS and the Cu(II) and Pb(II) ions removal
      capacity by MOCS in single-(non-competitive) and binary-(competitive) component
      sorption systems from aqueous solutions were investigated. The equilibrium data
      were analyzed using the Langmuir, Freundlich, Temkin and Redlich-Peterson
      isotherms. The characteristic parameters for each isotherm were determined. The
      Langmuir and Redlich-Peterson isotherms provided the best correlation for both
      Cu(II) and Pb(II) onto MOCS. From the Langmuir isotherms, maximum adsorption
      capacities of MOCS towards Cu(II) and Pb(II) are determined at different
      temperature. The maximum adsorption capacity of Cu(II) and Pb(II) per gram MOCS
      in single component sorption systems were from 5.91 and 7.71 micromol to 7.56 and
      9.22 micromol for the temperature range of 288-318 K, respectively. The order of
      affinity based on a weight uptake by MOCS was as follows: Pb(II)>Cu(II). The same
      behavior was observed during competitive adsorption that is in the case of
      adsorption from their binary solution. The thermodynamic parameters (DeltaG
      degrees , DeltaH degrees , and DeltaS degrees) for Cu(II) and Pb(II) sorption on
      MOCS were also determined from the temperature dependence. This competitive
      adsorption showed that the uptake of each metal was considerably reduced with an
      increasing concentration of the other, the adsorption of Cu(II) being more
      strongly influenced by Pb(II) than vice versa due to the higher affinity of MOCS
      for the latter.

PMID- 16631306
TI  - Competing approaches to excitotoxic neuroprotection by inert and catalytic
      antioxidant porphyrins.
AB  - The goal of this study was to determine if novel porphyrins protect cultured
      cortical neurons from excitotoxic NMDA exposure or oxygen-glucose deprivation
      (OGD), which model key aspects of cerebral ischemia. Porphyrins were chosen based
      on conventional and unconventional criteria. Metalloporphyrin catalytic
      antioxidants possessing a redox-sensitive metal core can exhibit potent and wide
      ranging catalytic antioxidant abilities, which are conventionally believed to
      underlie neuroprotection. We report here that a recent-generation potent
      peroxynitrite decomposition catalyst, FP-15, protected a majority of neurons
      against OGD and NMDA toxicity, without suppressing NMDA-mediated intracellular
      Ca2+ (Cai2+) elevations or whole-cell currents. We have previously shown that
      neuroprotection against OGD and NMDA toxicity correlated with an ability to
      suppress neurotoxic Cai2+ elevations and not antioxidant ability. We now evaluate
      if this unconventional mechanism extends to inert metal-free porphyrins. Neuron
      cultures were completely protected against OGD and NMDA toxicity by H2-meso
      tetrakis(3-benzoic acid)porphyrin (H2-TBAP(3)) or H2-meso-tetrakis(4
      sulfonatophenyl)porphyrin (H2-TPPS(4)), although only H2-TPPS(4) suppressed
      (completely) NMDA-induced Cai2+ rises. H2-meso-tetrakis(3,3'-benzoic
      acid)porphyrin (H2-TBAP(3,3')) or H2-meso-tetrakis(N-methylpyridynium-4
      yl)porphyrin (H2-TM-PyP(4)) provided at least partial protection against OGD and
      NMDA toxicity and partially suppressed NMDA-induced Cai2+ elevations. Despite the
      complexity of Ca2+-independent and -dependent based mechanisms, the inventory of
      porphyrins demonstrating neuroprotection in ischemia-relevant insults is now
      expanded to include FP-15 and inert metal-free compounds, although with no
      apparent advantage gained by using FP-15.

PMID- 16631307
TI  - Effect of L-DOPA on nitric oxide production in striatum of freely mobile mice.
AB  - In Parkinson's disease, nitric oxide (NO) and other free radicals are thought to
      be involved in neuronal degeneration. Furthermore, L-DOPA is suggested to have a
      cytotoxic action on dopaminergic neurons. We studied 24-h NO production and the
      effect of L-DOPA on this in freely mobile mice using in vivo microdialysis. A
      microdialysis probe was implanted into the right striatum 12 h before the
      experiment. This dialysis probe was perfused with Ringer solution for 100 min,
      then with 20, 50, or 100 nM L-DOPA for 20 min, and finally with Ringer solution.
      Dialysate fractions were collected every 20 min for 4 h. Production of nitrite
      and total NO were significantly higher during daytime than during nighttime.
      Nitrate production was increased significantly by L-DOPA. NO production in the
      striatum appears to exhibit a diurnal rhythm and to increase with exposure to L
      DOPA.

PMID- 16631308
TI  - Phenotypical analysis of adult rat olfactory ensheathing cells on 3-D collagen
      scaffolds.
AB  - Olfactory ensheathing cell (OEC) transplantation is a promising or potential
      therapy for spinal cord injury (SCI). However, the effects of injecting OECs
      directly into SCI site have been limited and unsatisfied due to the complexity of
      SCI. To improve the outcome, proper biomaterials are thought to be helpful since
      these materials would allow the cells to grow three-dimensionally and guide cell
      migration. In this paper, we have studied the behavior of OECs in two-dimensional
      (2-D) condition as well as on three-dimensional (3-D) collagen scaffolds by
      analyzing their phenotypes such as cell proliferation, apoptosis, morphology, and
      gene activities of some neurotrophic factors and myelin proteins. OECs
      proliferation rate was increased on 3-D collagen scaffolds compared to the 2-D
      culture condition. OECs on 3-D collagen scaffolds also showed less apoptosis. In
      addition, OECs on 3-D collagen scaffolds maintained the original spindle-shape
      morphology and P75NTR gene activity. NGF, BDNF, and PLP were found to be
      upregulated in OECs cultured on 3-D collagen scaffolds by the semi-quantitative
      RT-PCR approach. The results suggested that 3-D collagen scaffolds provide
      suitable environments for the OECs to maintain their morphology as well as
      several important functional phenotypes and all these could be helpful for the
      effective treatment of SCI.

PMID- 16631310
TI  - Selective metal binding by Vanabin2 from the vanadium-rich ascidian, Ascidia
      sydneiensis samea.
AB  - Vanadium-binding proteins, or Vanabins, have recently been isolated from the
      vanadium-rich ascidian, Ascidia sydneiensis samea. Recent reports indicate that
      Vanabin2 binds twenty V(IV) ions at pH 7.5, and that it has a novel bow-shaped
      conformation. However, the role of Vanabin2 in vanadium accumulation by the
      ascidian has not yet been determined. In the present study, the effects of acidic
      pH on selective metal binding to Vanabin2 and on the secondary structure of
      Vanabin2 were examined. Vanabin2 selectively bound to V(IV), Fe(III), and Cu(II)
      ions under acidic conditions. In contrast, Co(II), Ni(II), and Zn(II) ions were
      bound at pH 6.5 but not at pH 4.5. Changes in pH had no detectable effect on the
      secondary structure of Vanabin2 under acidic conditions, as determined by
      circular dichroism spectroscopy, and little variation in the dissociation
      constant for V(IV) ions was observed in the pH range 4.5-7.5, suggesting that the
      binding state of the ligands is not affected by acidification. Taken together,
      these results suggest that the reason for metal ion dissociation upon
      acidification is attributable not to a change in secondary structure but, rather,
      that it is caused by protonation of the amino acid ligands that complex with
      V(IV) ions.

PMID- 16631311
TI  - Adenosine 2b receptor (A2bR) signals through adenylate cyclase (AC) 6 isoform in
      the intestinal epithelial cells.
AB  - Adenosine 2b receptor (A2bR), a G-protein coupled receptor positively coupled to
      adenylate cyclase, mediates key events such as chloride, IL-6 and fibronectin
      secretion in intestinal epithelial cells and is upregulated during intestinal
      inflammation. In order to gain insight into the overall mechanism of A2bR
      activation, in this study, we sought to characterize the AC isoform associated
      with A2bR signaling. The colonic epithelial cell line T84, expressing only the
      A2b subtype of adenosine receptor, and Chinese hamster ovary (CHO) cells, were
      used in these studies. cAMP was measured by luminometric assay and AC isoform
      expression was determined by Western blot, RT-PCR, isoform-specific stealth RNAi
      and Quantigene. T84 and CHO cells express all nine known AC isoforms. In order to
      characterize which AC isoform(s) are associated with A2bR, we used the
      differential inhibition of specific AC isoforms by calcium and nitric oxide.
      Pretreatment of cells with carbachol or nitric oxide donors such as S-Nitroso-N
      acetylpencillamine (SNAP) and PAPANANOATE inhibited A2bR mediated increase in
      cAMP. Further, overexpression of AC-5 or AC-6 potentiated A2bR-mediated increases
      in cAMP levels. Finally, transfection with AC isoform-specific RNAi demonstrated
      that AC-6 but not AC-5 RNAi inhibited adenosine-induced cAMP levels. Taken
      together, these results suggest that A2bR mediates signaling through AC-6
      isoform. Since pro-inflammatory cytokines such as interferon-gamma (IFN-gamma)
      modulate the expression of specific AC isoforms in the intestinal epithelia, our
      observation may have therapeutic implications for intestinal inflammation or
      diarrhea wherein aA2bR is upregulated.

PMID- 16631312
TI  - Temporal sequence of changes in electrophysiological properties of oculomotor
      motoneurons during postnatal development.
AB  - The temporal sequence of changes in electrophysiological properties during
      postnatal development in different neuronal populations has been the subject of
      previous studies. Those studies demonstrated major physiological modifications
      with age, and postnatal periods in which such changes are more pronounced. Until
      now, no similar systematic study has been performed in motoneurons of the
      oculomotor nucleus. This work has two main aims: first, to determine whether the
      physiological changes in oculomotor nucleus motoneurons follow a similar time
      course for different parameters; and second, to compare the temporal sequence
      with that in other neuronal populations. We recorded the electrophysiological
      properties of 134 identified oculomotor nucleus motoneurons from 1 to 40 days
      postnatal in brain slices of rats. The resting membrane potential did not
      significantly change with postnatal development, and it had a mean value of -61.8
      mV. The input resistance and time constant diminished from 82.9-53.1 M omega and
      from 9.4-4.9 ms respectively with age. These decrements occurred drastically in a
      short time after birth (1-5 days postnatally). The motoneurons' rheobase
      gradually decayed from 0.29-0.11 nA along postnatal development. From birth until
      postnatal day 15 and postnatal day 20 respectively, the action potential
      shortened from 2.3-1.2 ms, and the medium afterhyperpolarization from 184.8-94.4
      ms. The firing gain and the maximum discharge increased with age. The former rose
      continuously, while the increase in maximum discharge was most pronounced between
      postnatal day 16 and postnatal day 20. We conclude that the developmental
      sequence was not similar for all electrophysiological properties, and was unique
      for each neuronal population.

PMID- 16631313
TI  - Homeostatic behavior of fast Fourier transform power in very low frequency non
      rapid eye movement human electroencephalogram.
AB  - Basic research shows that the physiological and molecular mechanisms of very low
      frequency (<1 Hz) electroencephalogram (EEG) waves of non-rapid eye movement
      (NREM) sleep differ from those of the higher (1-4 Hz) delta frequencies. Human
      studies show that the across-NREM period dynamics of very low frequency and 1-4
      Hz EEG also differ. These differences and the reported failure of very low
      frequency EEG power to increase after a night of total sleep deprivation raise
      the question of whether very low frequency EEG shows the other homeostatic
      properties established for higher delta frequencies. Here we tested the relation
      of very low frequency EEG power density to prior waking duration across a normal
      day and whether these low frequencies meet another criterion for homeostatic
      sleep EEG: conservation of power across a late nap and post-nap sleep. Data from
      19 young adults recorded in four separate sessions of baseline, daytime nap and
      post-nap sleep were analyzed. Power density in very low frequency NREM EEG
      increased linearly when naps were taken later in the day (i.e. were preceded by
      longer waking durations). In the night following an 18:00 h nap, very low
      frequency power was reduced by roughly the amount of power in the nap. Thus, very
      low frequency EEG meets two major homeostatic criteria. We hypothesize that these
      low frequencies reflect the executive rather than the functional processes by
      which NREM sleep reverses the effects of waking brain activity.

PMID- 16631314
TI  - The injury response of oligodendrocyte precursor cells is induced by platelets,
      macrophages and inflammation-associated cytokines.
AB  - Oligodendrocyte precursor cells recognized with the NG2 antibody respond rapidly
      to CNS injuries with hypertrophy and upregulation of the NG2 chondroitin sulfate
      proteoglycan within 24 h. These cells participate in glial scar formation,
      remaining around the injury site for several weeks. After injury, reactive
      oligodendrocyte precursor cells increase their production of several chondroitin
      sulfate proteoglycans, including NG2: this cell type thus represents a component
      of the inhibitory environment that prevents regeneration of axons in the injured
      CNS. This study analyzes factors that activate oligodendrocyte precursor cells.
      Both microglia and astrocytes become reactive around motor neurons following
      peripheral nerve lesions. We show that oligodendrocyte precursor cells do not
      hypertrophy or increase NG2 levels after these lesions. Those lesions that cause
      an oligodendrocyte precursor cell reaction generally open the blood-brain
      barrier. We therefore opened the blood-brain barrier with microinjections of
      vascular endothelial growth factor or lipopolysaccharide to the rat and mouse
      brain, and examined oligodendrocyte precursor cell reactivity after 24 h. Both
      treatments led to increases in NG2 and hypertrophy of oligodendrocyte precursor
      cells. Of directly injected blood components serum and thrombin were without
      effect, while platelets and macrophages activated oligodendrocyte precursor
      cells. We tested the effects of a range of injury-related cytokines, of which
      tumor necrosis factor alpha; interleukin-1; transforming growth factor beta;
      interferon gamma had effects on oligodendrocyte precursor cells. Oligodendrocyte
      precursor cell chemokines, and mitogens did not increase NG2 levels.

PMID- 16631315
TI  - Cortical changes to experimental sensitization of the human esophagus.
AB  - Topographical organization in the neocortex shows experience-dependent
      plasticity. We hypothesized that experimental sensitization of the esophagus
      results in changes of the topographical distribution of the evoked potentials and
      the corresponding dipole source activities to painful stimulation. An endoscopic
      method was used to deliver 35 electrical stimuli at the pain threshold to a fixed
      area of the mucosa in 10 healthy volunteer men and women. The stimulations were
      repeated after 30 min (reproducibility experiment), and after 60 min following
      perfusion of 200 ml 0.1 N hydrochloric acid (sensitization experiment). During
      stimulation the electroencephalogram was recorded from 64 surface electrodes. The
      sensitization resulted in a decrease in the pain threshold (F=6.2; P=0.004). The
      topographic distribution of the evoked potentials showed reproducible negative
      (N1, N2) and positive (P1, P2) components. After acid perfusion a reduced latency
      and a change in localization was seen for the P1 subdivided into frontal and
      occipital components (F=29.5, P<0.001; F=53.7, P<0.001). Furthermore the
      sensitization resulted in a reduction of the latency for P2 (F=6.2, P=0.009). The
      source analysis showed consistent dipolar activity in the bilateral opercular
      insular cortex before and after acid perfusion. For the anterior cingulate dipole
      there was a reduction in latency (P=0.03) and a posterior shift (P=0.0002)
      following acid perfusion. The findings indicate that short-term sensitization of
      the esophagus results in central neuroplastic changes involving the cingulate
      gyrus, which also showed pathological activation in functional diseases of the
      gut, thus reflecting the importance of this region in visceral pain and
      hyperalgesia.

PMID- 16631316
TI  - Pathophysiological factors underlying heatstroke.
AB  - Heatstroke is a life-threatening illness characterized by an elevated core body
      temperature (>40 degrees C) and dysfunction of central nervous system, which
      results in delirium, convulsions, or coma. Despite adequate hypothermia or other
      care-therapy, heatstroke is often fatal. On the basis of our knowledge of the
      pathophysiology on heatstroke, we hypothesized that heatstroke is a form of
      hyperthermia associated with the acute physiological alterations, the
      cytotoxicity of heat, systemic inflammatory response, oxidative damage and
      attenuated heat-shock response leading to a syndrome of multi-organ dysfunction.
      In view of above-mentioned situation, the physiological factors underlying
      heatstroke and the corresponding possible therapeutic strategies to avert the
      complications of this disorder would be summarized in this review so as to
      provide some therapeutic guidelines for heatstroke. Heatstroke is a very
      complicated process. Acute physiological alterations, such as low arterial
      hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral
      ischemia, and increased intracellular metabolism rate, occurred while exposed to
      a high ambient temperature. Hyperpyrexia caused cytotoxicity, resulting the
      degradation and aggregation of extensive intracellular proteins, influencing the
      change of membrane stability and fluidity, damaging the transmembrane transport
      of protein and the function of surface receptor, and inducing different
      cytoskeletal changes. Heatstroke resembles sepsis in many aspects, and
      endotoxemia and cytokines may be implicated in its pathogenesis. The
      concentration of interleukin-6 was positively correlated with the severity of
      heatstroke. The excessive accumulation of cytotoxic free radicals and oxidative
      damage may occur in the brain tissues during the genesis and development of
      heatstroke. The circulatory shock and cerebral ischemia resultant from heatstroke
      correlated closely with the free radicals (especially free radicals of peroxide
      and superoxide), the peroxidation of lipids, and low activity of antioxidase in
      the brain. Heat-shock proteins (Hsps) played a critical role during the process
      obtaining thermotolerance, therefore, protected from stress-induce cellular
      damage. Host factors or physiologically limiting factors, for instance, aging,
      existing illness, dehydration, deep insomnia, lack of acclimation to heat,
      inadequate physical fitness, and certain genetic polymorphisms were associated
      with a low level of Hsps expression and might favor the progression from heat
      stress to heatstroke. Some measures, such as molecular chaperonines, anti
      inflammatory agents, antioxidant agents, and modulators of Hsps would be good for
      the patients with heatstroke.

PMID- 16631317
TI  - Clonality of clinical methicillin-resistant Staphylococcus epidermidis isolates
      in a neonatal intensive care unit.
AB  - OBJECTIVE: Study of the clonality of methicillin-resistant Staphylococcus
      epidermidis responsible of epidemic infections in a neonatal intensive care unit.
      PATIENTS AND METHODS: All S. epidermidis isolates (mecA+) were collected during
      the epidemic period (December 2003-September 2004) from different pathological
      products of newborns. Isolates were characterized by genotyping in pulsed-field
      gel electrophoresis and by electrophoretic profiles obtained by PCR-based
      analysis of inter-IS256 spacer polymorphisms. RESULTS: Twenty methicillin
      resistant S. epidermidis isolates were collected from newborns during the
      epidemic period and represented 41.6% of the total isolates of S. epidermidis,
      which is the first Staphylococcus species isolated from the unit. These isolates
      were collected from blood cultures (80%), vascular catheters (5%), pus (10%), and
      intra-tracheal tube (5%). Six genotypic profiles were individualized: type A,
      type B, type C, type D, type E, and type F, with clear dominance of type A. Five
      different PCR patterns were found with poor correlation to genotypes defined by
      PFGE. CONCLUSION: Neonatal nosocomial outbreak of methicillin-resistant S.
      epidermidis was caused by multiple clones of this species with predominance of
      one epidemic and multiresistant clone. This clone may be transmitted between
      babies and was able to persist in the unit. PCR IS 256 proved to be less
      discriminative than PFGE for typing MRSE.

PMID- 16631318
TI  - [Contamination with Sphingomonas paucimobilis: about seven cases isolated in
      conservation and transport mediums of corneal grafts].
AB  - From September to December 2004, contaminations were found in fifteen
      conservation and transport mediums of corneal grafts at the tissue bank of Brest,
      including seven by Sphingomonas paucimobilis. The pulsed-field gel
      electrophoresis made it possible to establish the genotypic profiles of each
      strain and to compare them. Similarities were found between certain strains of
      the contaminated mediums and those of the thermostated double boiler of the
      tissue bank. The link between the contamination and the defrosting of the mediums
      in the double boiler was thus established. Measures of prevention are currently
      proposed to defrost the bottles like the use of a dry bath to replace the current
      one.

PMID- 16631319
TI  - [Biologic effects of millimeteric waves (94 GHz). Are there long term
      consequences?].
AB  - Active Denial Systems (ADS) is a millimetric wave radiation emitting technology
      now included in the non lethal weapon arsenal. Such devices emit electromagnetic,
      thus agitating water in the skin and causing feeling of heat enough that target
      individual retreats from the beam. They can be used at up to 1 km from the
      target. We have reviewed the literature on the interactions of millimetric waves
      (MMW) with biological systems. An opposition appears between the observations
      performed in the Former Soviet Union and Russia showing potential interaction
      sometimes deleterious while generally of good influence and used in therapy. By
      way of contrast, most of the other studies, performed in USA, address local acute
      effects, exclusively located on the skin and eyes of the target, and considered
      as completely reversible.

PMID- 16631320
TI  - [Use of combined detection of hepatitis C virus core antigen and antibodies to
      reduce the serological window-phase].
AB  - OBJECTIVES: In this study, we aimed at evaluating the performances of a combined
      assay for the detection of hepatitis C virus core antigen and antibodies and
      comparing this test with conventional third generation Elisa. MATERIAL AND
      METHODS: Two hundred forty-one samples were included in this study and tested by
      Monolisa HCV Ag-Ab ULTRA, Biorad and compared to Monolisa Anti-HCV Plus. A
      comparative study was performed on a HCV seroconversion panel (Monolisa anti-HCV
      Plus, Biorad; Innotest HCV Ab IV, Innogenetics and Murex anti-HCV, Abbott). False
      positive samples were detected with western blot assay (INNO-LIA HCV Ab III,
      Innogenetics). Two anti-HCV negative haemodialysis patients with rise in ALT have
      been tested for RNA detection (Amplicor v2.0, Roche). RESULTS: Results obtained
      with Biorad Ag-Ab were in agreement with third generation ELISA on HCV
      seroconversion panel. From anti-HCV negative patients, four samples were found
      low positive with HCV Ag-Ab. Two anti-HCV negative haemodialysis patients/HCV RNA
      positive were also negative with HCV Ag-Ab and 13 low positive samples with
      Biorad Ab were found negative with Ag-Ab. CONCLUSION: The HCV Ag-Ab assay has a
      high specificity and sensitivity comparatively to conventional ELISA; but in our
      study we don't prove the reduction of the "serologic window" for detection of
      anti-HCV antibodies.

PMID- 16631321
TI  - Momentary maximizing and optimal foraging theories of performance on concurrent
      VR schedules.
AB  - Optimal foraging theory proposes that animals obtain the highest rate of
      reinforcers for the least effort and momentary maximizing theory proposes that
      animals make the response that at that instant is most likely to be reinforced.
      While each theory may account for matching on concurrent schedules, the data
      supporting each theory are weak. Two experiments assessed these theories by
      considering concurrent choice as consisting of two pairs of stay and switch
      schedules. Symmetrical arrangements, which are equivalent to standard concurrent
      schedules, maintained behavior described by the generalized matching law.
      Weighted arrangements, in which the programmed rate of earning reinforcers was
      always greater at one alternative, maintained behavior that was biased towards
      the weighted alternative, yet the bias was less than that predicted by optimal
      foraging theory. Asymmetrical arrangements, in which the stay and switch
      schedules operating at an alternative are the same, maintained behavior that
      favored one alternative, even though momentary maximizing predicted indifference.
      The generalized matching law poorly described each rat's pooled data from all
      conditions but these data were described by an equation based on the stay and
      switch reinforcers earned per-visit and included elements of optimal foraging and
      momentary maximizing theories of choice.

PMID- 16631322
TI  - Short-term item memory in successive same-different discriminations.
AB  - Pigeons were tested in a successive same-different (S/D) discrimination procedure
      to examine the short-term memory for individual items in sequences of different
      or identical pictures. Item-by-item analyses of pecking behavior within single
      trials revealed this S/D discrimination emerged at the earliest possible point in
      the sequence--the presentation of the second item. Further, by comparing peck
      rates at points where different types of sequences diverged (e.g. ABA versus
      ABC), we determined that the pigeons remembered the first item for at least 4-8s
      and across one to two intervening items. These results indicate that this S/D
      discrimination was controlled by relational comparisons of pictorial content
      across memories of specific items, rather than the detection of low-level
      perceptual "transients" between items. A second experiment supported this
      conclusion by showing increased discrimination with longer first item viewing
      times, consistent with encoding of details about individual pictures. These
      findings further support a qualitative similarity among birds and primates in
      possessing a general capacity to judge certain types of stimulus relations, such
      as stimulus identity and difference. Implications for the temporal continuity of
      experience in animals are also considered.

PMID- 16631323
TI  - A preliminary randomized, double-blind, placebo-controlled study of the safety
      and efficacy of ondansetron in the treatment of cocaine dependence.
AB  - Prior studies have demonstrated inefficacy among dopamine receptor antagonists
      for treating cocaine dependence. An alternative approach would be to investigate
      the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such
      as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing
      effects. We hypothesized that ondansetron might be more efficacious than placebo
      at reducing cocaine intake and promoting abstinence in cocaine-dependent
      individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63
      treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg,
      1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week,
      participants were assessed on several measures of cocaine use, including urine
      benzoylecgonine. Cognitive behavioral therapy was administered weekly.
      Ondansetron was well tolerated, causing no serious adverse events. The
      ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups
      and a greater rate of improvement in percentage of participants with a cocaine
      free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0
      mg group had a lower rate of improvement in percentage of weekly mean non-use
      days than did placebo recipients (p = 0.04). These results suggest the
      possibility of a non-linear dose-response function, with evidence supporting
      efficacy for the 4.0 mg group.

PMID- 16631324
TI  - Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ.
AB  - Primary microcephaly is a developmental defect of the brain characterized by
      severely reduced brain size but an absence of other overt abnormalities.
      Mutations in several loci have been linked to primary microcephaly. The
      underlying genes for two of these were recently identified as CDK5RAP2 and CENPJ.
      Here, we focus on CDK5RAP2 and show that the protein evolutionary rate of this
      gene is significantly higher in primates than rodents or carnivores. We further
      show that the evolutionary rate within primates is particularly high in the human
      and chimpanzee terminal branches. Thus, the pattern of molecular evolution seen
      in CDK5RAP2 appears to parallel, at least approximately, that seen in two other
      previously identified primary microcephaly genes, microcephalin and ASPM. We also
      briefly discuss CENPJ, which similarly exhibits higher rate of protein evolution
      in primates as compared to rodents and carnivores. Together, the evolutionary
      patterns of all four presently known primary microcephaly genes are consistent
      with the hypothesis that genes regulating brain size during development might
      also play a role in brain evolution in primates and especially humans.

PMID- 16631325
TI  - Characterization of the murine Inpp4b gene and identification of a novel isoform.
AB  - Inositol polyphosphate phosphatases and phosphoinositides second messengers have
      been associated with major cellular functions as growth, differentiation,
      apoptosis, protein trafficking and motility. To characterize the role of inositol
      phosphatases in cell physiology, we have isolated the mouse Inositol
      polyphosphate 4-phosphatase type II (Inpp4b) cDNA. The murine Inpp4b locus was
      mapped on chromosome 8 in a synthenic region of the human 4q27-31 interval
      between Il-15 and Usp38. The mouse Inpp4b proteins, alpha and beta isoforms,
      encoded by this locus contained 927 and 941 amino acids respectively with a
      consensus phosphatase catalytic site and a conserved C2 domain that are highly
      similar with the human and rat homologues. Interestingly, we characterized a
      novel shorter isoform of Inpp4balpha resulting from an alternative translation
      initiation site and exon 5 skipping. Inpp4b C2 domain interacted with
      preferential affinity to phosphatidic acid and phosphatidylinositol 3,4,5
      triphosphate (PI(3,4,5)P(3)) lipids. While analysis of Inpp4b transcript and
      protein expression demonstrated a broad tissue distribution for the alpha
      isoform, as for the paralogue Inpp4aalpha and beta isoforms, it also displayed a
      limited hematopoietic lineage distribution whereas the Inpp4bbeta isoform had a
      highly restricted pattern. Importantly, the Inpp4bbeta localized to the Golgi
      apparatus whereas Inpp4balpha was mainly cytosolic, suggesting a different
      cellular function for this isoform. Together our characterization of the murine
      Inpp4b gene expression pattern, cellular sublocalization and interacting lipids
      support highly specific function for individual Inpp4 phosphatase proteins.

PMID- 16631326
TI  - The amplitude of the Achilles tendon reflex in infants is related to body
      position.
AB  - In this study, we investigated whether the Achilles tendon reflex (ATR) in
      healthy infants is modulated by changes in body position (prone vs. supine). The
      amplitude of the ATR was compared at postnatal day 1, months 2, 3 and 6, while
      infants were placed in prone and supine position. The ATR was considered
      "positive" when at least 1 of 20 tendon taps evoked a visible contraction of the
      ankle plantar flexor muscles. At 6 months, the amplitude and latency of the ATR
      were evaluated by electromyographic (EMG) recordings of the (lateral and medial)
      gastrocnemius muscle, with the infant in prone and supine position. At postnatal
      day 1, the clinical ATR response was more frequently present in prone than supine
      position (14/16 or 88% vs. 4/16 or 25%, respectively, p < 0.01). From 2 months
      onwards, the frequencies of positive ATRs were no longer significantly different
      between prone (14/14 or 100%) and supine position (10/14 or 67%). However, based
      on the EMG recordings at 6 months, the ATR amplitude was higher in prone compared
      to supine position (n=8, median 5.5 mV, range 4.7-6.6 mV; and median 3.8 mV,
      range 2.3-5.6 mV, p < 0.05). We conclude that the ATR response in healthy infants
      is more pronounced in prone than in supine position, either when clinically
      (visually) assessed during routine tendon tapping or when neurophysiologically
      assessed during surface EMG recording.

PMID- 16631327
TI  - Isolation, follicular density, and culture of preantral follicles of buffalo
      fetuses of different ages.
AB  - The aim of the present study was to determine the most desirable ovarian tissue
      section thickness to isolate preantral follicles (Experiment I), determine
      follicular density (follicles/mm(2) of cortex) of ovaries of fetal buffalo of
      different ages (Experiment II), and cultivate preantral follicles of buffalo
      fetuses (Experiment III). In Experiment I, ovary sections with different
      thicknesses (25, 50, 75, and 100 microm) had 415.0+/-285.2, 457.5+/-341.9,
      585.0+/-309.3, and 685.0+/-278.8 isolated preantral follicles, respectively. In
      Experiment II, the follicular density of 46 buffalo fetuses with ages between 3
      and 8 months was estimated to be between 0 and 7220, with means of 0.0, 2070.7+/
      2190.3, 2570.8+/-1796.6, 2298.1+/-2286.5, 1277.5+/-1074.9, and 643.6+/-543.9
      throughout the age range studied. The follicular density of 5-month-old fetuses
      was greatest, coinciding with the largest number of follicles isolated at this
      age. In Experiment III, preantral follicles isolated from the ovaries of buffalo
      fetuses aged from 5 to 9 months old were cultivated individually for 7 days in
      four different media: basic medium (Minimal Essential Medium (MEM), 10% SFB,
      kanamycin, pyruvate, glutamine, hypoxanthine) with additional ITS and FSH
      0.5mg/ml (treatment 1); basic medium with FSH and EGF 100 ng/ml (treatment 2);
      basic medium with additional ITS, FSH, and EGF (treatment 3); basic medium
      supplemented with ITS and EGF (treatment 4). Integrity and morphological
      features, viability, and increase in diameter of follicles cultured in vitro were
      evaluated individually with an inverted microscope and an ocular micrometer. The
      results showed that follicle structure and form were maintained during culture.
      Growth and survival rates of treatments 1, 2, and 3 over 7 day culture were
      23.25+/-17.06, 33.75+/-26.19, and 43.75+/-31.73 microm, and 31.3+/-22.7, 22.06+/
      8.13, and 28.92+/-21.32%, respectively. However, neither growth nor survival was
      observed in treatment 4. In conclusion, this study showed that preantral
      follicles of buffalo fetuses can be cultured in vitro, and that FSH is essential
      for follicle survival.

PMID- 16631328
TI  - Preparation and evaluation of oral solid heparin using emulsifier and adsorbent
      for in vitro and in vivo studies.
AB  - Oral anticoagulant therapy with heparin has been challenged by formulating
      heparin in oral solid preparation. As heparin, low molecular weight heparin
      (LMWH) was used. LMWH was dispersed with a surfactant used for the self
      microemulsifying drug delivery system (SMEDDS), PEG-8 caprylic/capric glycerides
      (Labrasol), and the mixture was solidified with three kinds of adsorbents,
      microporous calcium silicate (Florite RE), magnesium alminometa silicate
      (Neusilin US(2)) and silicon dioxide (Sylysia 320). The in vitro release study
      showed that the T50%s were 3.2+/-0.1min for Sylysia 320, 4.6+/-0.2min for Florite
      RE, 13.7+/-0.1min for Neusilin US(2). The in vivo rat absorption study showed
      that Florite RE system had the highest C(max), 0.42+/-0.01IU/mL and AUC, 0.59+/
      0.06IUh/mL, where plasma LMWH levels were measured as anti-Xa activity. Other
      preparations had the C(max) and AUC, 0.12+/-0.01IU/mL and 0.15+/-0.02IUh/mL for
      Neusilin US(2) and 0.25+/-0.02IU/mL and 0.40+/-0.03IUh/mL for Sylysia 320,
      respectively. The bioavailability (BA) of LMWH from the microporous calcium
      silicate preparation, Florite RE, was 18.8% in rats by comparing the AUC obtained
      after i.v. injection of LMWH, 40IU/kg to another group of rats. Florite RE system
      was evaluated in dogs after oral administration in an enteric capsule made of
      Eudragit S100 at the LMWH dose of 200IU/kg. High plasma anti-Xa activity levels
      were obtained, i.e., the C(max) was 0.48+/-0.11IU/mL and AUC was 1.64+/
      0.32IUh/mL. These results suggest that adsorbent system is useful as an oral
      solid delivery system of poorly absorbable drugs such as LMWH.

PMID- 16631329
TI  - Evaluation of brain-targeting for the nasal delivery of estradiol by the
      microdialysis method.
AB  - The uptake of estradiol into the cerebrospinal fluid (CSF) after intranasal and
      intravenous administration in rats was investigated to study whether direct nose
      CSF transport of estradiol exits or not. Animals received 0.48 mg kg(-1)
      estradiol randomly methylated beta-cyclodextrin (RAMEB) inclusion complex
      intranasally and intravenously. Following nasal delivery, estradiol reached a
      C(max) value (mean+/-S.D.) in plasma (26.70+/-11.37 ng ml(-1)) and CSF (54.76+/
      32.84 ng ml(-1)) after 20 min in each case, while after intravenous infusion,
      estradiol reached a C(max) value in plasma (170.08+/-64.67 ng ml(-1)) and CSF
      (26.48+/-11.34 ng ml(-1)) at 5 min and 60 min, respectively. The
      AUC(CSF)/AUC(plasma) ratio (1.60+/-0.67) after intranasal delivery differed
      significantly from the ratio (0.61+/-0.16) observed after intravenous infusion
      (P<0.05). All these results indicate that estradiol is transported into CSF via
      olfactory neurons, and, hence, there is a direct transport route from the nasal
      cavity into the CSF for estradiol.

PMID- 16631330
TI  - Predictive factors of treatment interruption duration in a cohort of HIV-1
      infected patients with CD4 count greater than 350 cells per mm3.
AB  - OBJECTIVE: To determine predictive factors of treatment interruption (TI)
      duration within a cohort of HIV-1 infected patients having stopped their
      treatment with CD4 above 350 cells per mm(3). DESIGN: Data were collected from
      computerized medical records. Patients were selected if they were HIV-1 positive,
      18 years of age or older, and had stopped their treatment between January 1st,
      1999 and July 1st, 2003, with CD4 count above 350 cells per mm(3). The study
      period was censored on October 1st, 2003. Patients were assessed every 3 months
      from inclusion to censure. A survival analysis using the Cox proportional hazard
      model was performed. RESULTS: One hundred eighty-five patients were included. The
      median duration of TI was 43 weeks. Sixty-three patients remained off-treatment
      at censure. In the multivariate analysis, TI duration was shorter if CD4 nadir
      was below 250 cells per mm(3) before TI (relative hazard, 2.10), age superior to
      40 (relative hazard, 1.72), viral load higher than 2.3 log.copies per ml
      (relative hazard, 1.52), and CDC class C (relative hazard, 1.78) at TI. Neither
      CD4 cell count at TI, numbers of treatments, nor duration of treatment and
      infection before TI were independent predictive factors of early treatment
      resumption (TR). CONCLUSION: Some clinical and biological data may be used as
      predictive factors of early TR. Our results can have implications on future
      therapeutic strategies, in which the goal of therapy is to maintain CD4 cell
      count above a predetermined threshold using cycles of therapy followed by
      prolonged interruption according to CD4 count.

PMID- 16631331
TI  - [Prevalence of Giardia intestinalis in a farming population using sewage water in
      agriculture, Settat, Morocco].
AB  - OBJECTIVE: This investigation was undertaken to assess the risk linked to the use
      of raw sewage waters in agriculture, and the prevalence of Giardia intestinalis.
      DESIGN: The survey was made on 214 individuals, average age 28.6+/-19.4 years,
      belonging to two douars using raw sewage waters in agriculture, and 119
      individuals, age 31.8+/-19.5 years, belonging to a control douar not using raw
      sewage waters. These three douars are located in around the city of Settat, in
      Morocco. Every consenting individual was given a complete clinical examination
      and 3 stools samples were collected in 3 consecutive days. RESULTS: The
      prevalence of G. intestinalis in the exposed population was 11.7% compared to
      2.5% in the control population. The relative risk was 4.6. This difference is
      statistically significant. The most concerned individuals were essentially
      children between 3 and 14 years of age. Close contact was an important factor of
      infection in the exposed population, with a higher prevalence in the case of high
      promiscuity index. In the exposed population, more than 50% of the cases were
      familial ones. Giardiasis causes a trophic state, essentially in children.
      CONCLUSION: The use of the raw sewage waters in agriculture is responsible for an
      increased risk of giardiasis. Some preventive measures are mandatory, including
      hygiene education and an adequate treatment of sewage waters.

PMID- 16631332
TI  - [Quorum sensing: a new clinical target for Pseudomonas aeruginosa?].
AB  - Pseudomonas aeruginosa is an opportunistic bacteria causing a wide variety of
      infections. The bacterial virulence depends on a large panel of cell-associated
      and extracellular factors. Quorum sensing (QS) allows cell-to-cell communication:
      sensing the environment, this system coordinates the expression of various genes
      within the bacterial population. QS is based on an interaction between a small
      diffusible molecule, an acylhomoserine lactone (AHL), and a transcriptionnal
      activator. Two QS systems, the las and rhl systems, have been identified in P.
      aeruginosa. The las system associates the transcriptionnal activator protein LasR
      and LasI responsible for the synthesis of a specific AHL: C12-HSL. This system
      was shown to activate the expression of a large number of virulence factors.
      Similarly, the rhl system associates the transcriptionnal activator protein RhlR
      with RhlI, which is responsible for the synthesis of another AHL: C4-HSL.
      Synthesis and secretion of a number of virulence factors are controlled by QS.
      Utilization of different animals models showed the crucial role of QS in the
      pathogenesis of P. aeruginosa infections. The discovery of QS has given a new
      opportunity to treat bacterial infection by another means than growth inhibition.
      New drugs inhibiting QS were recently discovered: furanone compounds can repress
      a large number of QS-regulated genes, including numerous P. aeruginosa virulence
      factor genes. Furanone administration to mice infected with P. aeruginosa
      significantly reduced lung bacterial load compared with the control group.

PMID- 16631333
TI  - [First case of infection due to vancomycin resistant Enterococcus faecalis in New
      Caledonia].

PMID- 16631334
TI  - Analysis of radiological features relative to histopathology in 42 skull-base
      chordomas and chondrosarcomas.
AB  - Chordomas and chondrosarcomas are malignant tumors that are reported to have
      similar clinical presentations and radiological features but different behaviors
      and outcomes. The aim of this retrospective study was to determine whether
      specific radiological features of skull-base chordomas or chondrosarcomas are
      correlated with histopathology, and thus allow preoperative diagnosis. The study
      involved 32 classic chordomas, 6 chondroid chordomas and 4 chondrosarcomas (42
      tumors total). For each case, tumor size and extent, the detailed anatomy
      involved, and magnetic resonance imaging and computed tomography findings were
      analyzed. Tumor extent was assessed using a novel method that assessed
      presence/absence in 18 defined skull-base zones. The chondrosarcomas presented
      significantly earlier in life than the chordomas (means, 20.5 years versus 36
      years, respectively). At time of diagnosis, the median tumor volume was 23 cm(3)
      (range, 1.2-78.8 cm(3)) and the mean tumor extent was 6.7+/-2.9 zones. There were
      no differences between chordomas and chondrosarcomas, or between the two chordoma
      subgroups, with respect to lesion volume or extent. Comparison of other imaging
      findings revealed no features that were diagnostic for either chordoma or
      chondrosarcoma. The data support previous claims that chondrosarcomas present
      earlier in life than chordomas, but this finding is not diagnostic. There is wide
      variation in the extent of skull-base chordomas and chondrosarcomas, and in the
      specific anatomical structures these tumors involve. None of the MRI or CT
      features of these tumors appear to be useful for differentiating chordomas from
      chondrosarcomas preoperatively. For surgical planning, specific, area-oriented
      definition of tumor extent might provide more useful information than tumor-type
      classification schemes.

PMID- 16631335
TI  - Method development and validation for isoflavones in soy germ pharmaceutical
      capsules using micellar electrokinetic chromatography.
AB  - The separation of six soy isoflavones (Glycitein, Daidzein, Genistein, Daidzin,
      Glycitin and Genistin) was approached by a 3(2) factorial design studying MEKC
      electrolyte components at the following levels: methanol (MeOH; 0-10%) and sodium
      dodecylsulfate (SDS; 20-70 mmol L(-1)); sodium tetraborate buffer (STB)
      concentration was kept constant at 10 mmol L(-1). Nine experiments were performed
      and the apparent mobility of each isoflavone was computed as a function of the
      electrolyte composition. A novel response function (RF) was formulated based on
      the production of the mobility differences, mobility of the first and last
      eluting peaks and the electrolyte conductance. The inspection of the response
      surface indicated an optimum electrolyte composition as 10 mmol L(-1) STB (pH
      9.3) containing 40 mmol L(-1) SDS and 1% MeOH promoting baseline separation of
      all isoflavones in less than 7.5 min. The proposed method was applied to the
      determination of total isoflavones in soy germ capsules from four different
      pharmaceutical laboratories. A 2h extraction procedure with 80% (v/v) MeOH under
      vortexing at room temperature was employed. Peak assignment of unknown
      isoflavones in certain samples was assisted by hydrolysis procedures, migration
      behavior and UV spectra comparison. Three malonyl isoflavone derivatives were
      tentatively assigned. A few figures of merit for the proposed method include:
      repeatability (n=6) better than 0.30% CV (migration time) and 1.7% CV (peak
      area); intermediate precision (n=18) better than 6.2% CV (concentration);
      recoveries at two concentration levels, 20 and 50 microg mL(-1), varied from 99.1
      to 103.6%. Furthermore, the proposed method exhibited linearity in the
      concentration range of 1.6-50 microg mL(-1) (r(2)>0.9999) with LOQ varying from
      0.67 to 1.2 microg mL(-1). The capsules purity varied from 93.3 to 97.6%.

PMID- 16631336
TI  - HPLC determination of phenolics adsorbed on yeasts.
AB  - An analytical HPLC method was developed to determine monomeric anthocyans as
      catechin (CA), flavonols as rutin (RU) and phenol acids as gallic acid (GA)
      adsorbed on the cell wall of 23 Saccharomyces cerevisiae strains grown on two
      media containing high levels of phenolic compounds, from grape seeds and grape
      skins, and on one control medium. Microbial biomass purification by liquid-liquid
      extraction of the phenolics is followed by reversed-phase chromatographic
      separation and CA, RU and GA detection by ultraviolet detector. The method was
      linear over the studied range of concentrations: GA at 0.12-0.96 microg/ml, CA at
      0.25-20.00 microg/ml and RU at 0.02-0.20 microg/ml. The correlation coefficient
      for each analyte was greater than 0.9983. The recovery was greater than 85% for
      both GA and RU, and greater than 94% for CA. The detection limits for GA, CA and
      RU were determined to be 0.015, 0.025 and 0.029 microg/mg of biomass,
      respectively. The proposed method is highly responsive for the determination of
      different phenolics, and seems to be useful to evaluate their adsorption profile
      on yeasts.

PMID- 16631337
TI  - Antimicrobial activity of tigecycline against recent isolates of respiratory
      pathogens from Asian countries.
AB  - In vitro activities of tigecycline were compared with 15 other comparator agents
      against recent clinical isolates of respiratory pathogens (623 Streptococcus
      pneumoniae, 105 Staphylococcus aureus, 92 Klebsiella pneumoniae, and 84
      Haemophilus influenzae isolates) collected from 11 Asian countries. All isolates
      of S. pneumoniae from Asian countries were susceptible to tigecycline regardless
      of penicillin susceptibility with MIC90 of <or=0.06 mg/L. Both methicillin
      resistant and methicillin-susceptible S. aureus isolates were susceptible to
      tigecycline with very low MIC90 values (0.25 and 0.12 mg/L, respectively).
      Tigecycline was also active against K. pneumoniae (98.9% susceptible; MIC50, 1
      mg/L; MIC90, 2 mg/L) including 10 extended-spectrum beta-lactamase-producing
      isolates and H. influenzae (100% susceptible; MIC50 and MIC90, 0.12 mg/L) from
      Korea. Data confirmed that tigecycline has an excellent in vitro activity against
      drug-resistant clinical isolates of respiratory pathogens from Asian countries.

PMID- 16631338
TI  - Antimicrobial susceptibility pattern comparisons among intensive care unit and
      general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test
      Information Collection Program (USA).
AB  - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program
      is a global, longitudinal antimicrobial resistance surveillance network of
      greater than 100 medical centers worldwide monitoring the susceptibility of
      bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999
      and 2002, 15 US medical centers referred up to 200 nonduplicate isolates from
      clinical infections to a central processing laboratory. During this 4-year
      period, the antimicrobial activity of 11 broad-spectrum agents was assessed
      against 5389 bacterial isolates using Clinical and Laboratory Standards Institute
      (formerly National Committee for Clinical Laboratory Standards)-recommended
      methods with interpretive criteria. Analysis of the MIC results for pathogens
      isolated from patients hospitalized in intensive care units (ICUs) were compared
      to results from pathogens isolated in non-ICU settings. Among Enterobacteriaceae
      (3884 strains), the carbapenems (imipenem and meropenem) demonstrated the highest
      susceptibility rates (> or =98.7%) and with only a 1% increase in resistance for
      ICU isolates compared to non-ICU organisms. Other antimicrobial agents tested
      demonstrated consistently higher susceptibility rates against Enterobacteriaceae
      isolates from ICU (89.7-98.7%) and non-ICU (93.2-99.9%) areas. For the
      nonfermentative Gram-negative bacilli, the rank order of the most active agents
      having lowest percentage resistance rates were tobramycin (15.5%) < cefepime <
      imipenem < piperacillin/tazobactam < ceftazidime < meropenem (21.9%) for ICU
      isolates, and meropenem (7.8%) < cefepime < imipenem < piperacillin/tazobactam <
      ceftazidime < tobramycin (12.9%) among non-ICU strains. All tested agents showed
      lower susceptibility rates (range, 1.0-15.3%) and higher resistance rates (range,
      0.1-15.1%) for both Enterobacteriaceae and nonfermentative Gram-negative bacilli
      among the ICU isolates compared to the non-ICU isolates (except for ciprofloxacin
      against Enterobacteriaceae). Continued surveillance of these broad-spectrum
      antimicrobial agents in both ICU and general hospital wards appears warranted to
      monitor the occurrence and spread of antimicrobial resistance in pathogens
      causing serious infections in these care areas and the possible emergence of
      resistance mechanisms that could compromise empiric carbapenem therapy.

PMID- 16631339
TI  - Ceftobiprole medocaril (BAL5788) treatment of experimental Haemophilus
      influenzae, Enterobacter cloacae, and Klebsiella pneumoniae murine pneumonia.
AB  - Ceftobiprole (BAL9141) is an investigational cephalosporin active against
      methicillin- and vancomycin-resistant staphylococci administered as a water
      soluble prodrug, ceftobiprole medocaril (BAL5788). Using an immunocompetent
      murine pneumonia model of Haemophilus influenzae, Enterobacter cloacae, or
      extended-spectrum beta-lactamase (ESBL) nonproducing or producing Klebsiella
      pneumoniae pneumonia, we compared results of treatment with ceftobiprole
      medocaril (71 mg/kg, sc, qid), ceftriaxone (50 mg/kg, im, bid), or cefepime (50
      mg/kg, ip, q.i.d.). Results were expressed as median and 25th to 75th percentile
      log10 colony forming units per gram of lung tissue. Ceftobiprole, ceftriaxone,
      and cefepime were each more active than was no treatment and were equally active
      for treatment of experimental H. influenzae, E. cloacae, or ESBL-nonproducing K.
      pneumoniae pneumonia. For ESBL-producing K. pneumoniae, no differences were
      detected between no treatment and treatment with ceftobiprole, ceftriaxone, or
      cefepime. Ceftobiprole is active against H. influenzae, E. cloacae, and ESBL
      nonproducing K. pneumoniae in an immunocompetent experimental murine pneumonia
      model.

PMID- 16631340
TI  - Risk factors for recurrence in patients with Staphylococcus aureus infections
      complicated by bacteremia.
AB  - Recurrence is a common complication of Staphylococcus aureus infections. A
      shorter duration of antibiotic treatment for a S. aureus infection has been
      previously suggested as a possible risk factor for recurrence. We conducted a
      retrospective cohort study of patients with S. aureus infection complicated by
      bacteremia who survived their initial treatment (N = 397) at the VA Maryland
      Health Care System from 1995 to 2004 to determine if 2 weeks or less of
      antibiotic therapy is significantly associated with a higher rate of recurrence.
      Recurrence was defined as recurrence of infection because of S. aureus with the
      same susceptibility to methicillin within 1 year of treatment of the initial
      bacteremia. Seventeen percent of patients who survived their initial infection
      had a recurrence of infection. Mean duration of antibiotic therapy in those who
      recurred was longer than in those who did not recur (21 versus 18 days, P = .18).
      No evidence was found to support an association between a duration of therapy of
      14 days or less and an increased risk for recurrence (RR, 0.68; 95% CI, 0.44
      1.04). However, being HIV infected (OR, 4.59; 95% CI, 1.61-13.10), having
      diabetes (OR, 2.02; 95% CI, 1.13-3.61) and having an infection due to a
      methicillin-resistant S. aureus (MRSA) (OR, 2.11; 95% CI, 1.17-3.80) were
      independent risk factors for recurrence. In conclusion, 2 weeks or less of
      antibiotic therapy was not associated with an increased risk for recurrence.
      However, patients with diabetes or HIV infection and patients with MRSA
      infections are at an increased risk for recurrence and should be followed more
      closely.

PMID- 16631341
TI  - Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of
      debilitating malignant ascites.
AB  - AIM: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy
      (LIPHC) in the treatment of malignant ascites. METHODS: From September 2001 to
      December 2003, 14 patients between the age of 56 and 78years were treated.
      Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian
      cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case).
      The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution
      as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending
      on the type of primary tumor. The drains were left in situ after surgery and
      removed when perfuse drainage ceased. RESULTS: Ascites was controlled in all the
      treated cases. A CT scan performed in follow-up showed a small, clinically
      undetectable, fluid accumulation in the pelvis of one patient. CONCLUSIONS: This
      method resulted in benefit for those peritoneal carcinomatosis patients with
      debilitating malignant ascites who were excluded from cytoreductive surgery.
      Proficiency in laparoscopic staging procedures and experience in the management
      of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are
      required for the success of the procedure.

PMID- 16631342
TI  - A new technique to assess dermal absorption of volatile chemicals in vitro by
      thermal gravimetric analysis.
AB  - Potential health hazards of dermal exposure, variability in reported dermal
      absorption rates and potential losses from the skin by evaporation indicate a
      need for a simple, inexpensive and standardized procedure to measure dermal
      absorption and desorption of chemical substances. The aim of this study was to
      explore the possibility to measure dermal absorption and desorption of volatile
      chemicals using a new gravimetric technique, namely thermal gravimetric analysis
      (TGA), and trypsinated stratum corneum from pig. Changes in skin weight were
      readily detected before, during and after exposure to vapours of water, 2
      propanol, methanol and toluene. The shape and height of the weight curves
      differed between the four chemicals, reflecting differences in diffusivity and
      partial pressure and skin:air partitioning, respectively. As the skin weight is
      highly sensitive to the partial pressure of volatile chemicals, including water,
      this technique requires carefully controlled conditions with respect to air flow,
      temperature, chemical vapour generation and humidity. This new technique may help
      in the assessment of dermal uptake of volatile chemicals. Only a small piece of
      skin is needed and skin integrity is not necessary, facilitating the use of human
      samples. The high resolution weight-time curves obtained may also help to
      elucidate the characteristics of absorption, desorption and diffusion of
      chemicals in skin.

PMID- 16631343
TI  - Evolution of the vertebrate ABC gene family: analysis of gene birth and death.
AB  - Vertebrate evolution has been largely driven by the duplication of genes that
      allow for the acquisition of new functions. The ATP-binding cassette (ABC)
      proteins constitute a large and functionally diverse family of membrane
      transporters. The members of this multigene family are found in all cellular
      organisms, most often engaged in the translocation of a wide variety of
      substrates across lipid membranes. Because of the diverse function of these
      genes, their large size, and the large number of orthologs, ABC genes represent
      an excellent tool to study gene family evolution. We have identified ABC proteins
      from the sea squirt (Ciona intestinalis), zebrafish (Danio rerio), and chicken
      (Gallus gallus) and, using phylogenetic analysis, identified those genes with a
      one-to-one orthologous relationship to human ABC proteins. All ABC protein
      subfamilies found in Ciona and zebrafish correspond to the human subfamilies,
      with the exception of a single ABCH subfamily gene found only in zebrafish.
      Multiple gene duplication and deletion events were identified in different
      lineages, indicating an ongoing process of gene evolution. As many ABC genes are
      involved in human genetic diseases, and important drug transport phenotypes, the
      understanding of ABC gene evolution is important to the development of animal
      models and functional studies.

PMID- 16631344
TI  - A novel RNAi library based on partially randomized consensus sequences of nuclear
      receptors: identifying the receptors involved in amyloid beta degradation.
AB  - Combinatorial gene inactivation using an RNAi library is a powerful approach to
      discovering novel functional genes. However, generation of a comprehensive RNAi
      library remains technically challenging. In this report, we describe a simple and
      novel approach to designing gene-family-specific RNAi libraries by targeting
      conserved motifs using degenerate oligonucleotides. We created an siRNA library
      in the pHUMU vector using partially randomized sequences targeting the consensus
      region in the ZnF_C4 signature motif of the nuclear hormone receptors and thus
      against the entire receptor superfamily. For proof of principle, we adapted a
      reporter assay to screen this library for receptors that might be involved in
      reducing amyloid beta peptide accumulation. We modified a previously described
      luciferase reporter assay to measure the amyloid beta precursor cleavages
      occurring only between beta- and gamma-secretase cleavage sites, thus excluding
      the major gamma-secretase activities that could generate neurotoxic Abeta
      peptides. Our screen using this assay identified siRNA vectors that specifically
      increase the Abeta40/42 cleavage and pointed to a potential receptor target, ROR
      gamma. SiRNAs targeting other regions of ROR-gamma not only confirmed the
      observed reporter activity but also reduced the level of the toxic Abeta
      peptides. The results demonstrated a general principle for the creation and
      application of this RNAi library approach for functional gene discovery within a
      predefined protein family. The discovered negative effect of ROR-gamma on the
      degradation of the toxic Abeta peptides may also provide a potential drug target
      or targetable pathway for intervention of Alzheimer disease.

PMID- 16631345
TI  - A humanized BAC transgenic/knockout mouse model for HbE/beta-thalassemia.
AB  - Hemoglobin E (HbE) is caused by a G-->A mutation at codon 26 of the beta-globin
      gene, which substitutes Glu-->Lys. This mutation gives rise to functional but
      unstable hemoglobin and activates a cryptic splice site causing mild anemia. HbE
      reaches a carrier frequency of 60-80% in some Southeast Asian populations. HbE
      causes serious disease when co-inherited with a beta-thalassemia mutation. In
      this study, we report the creation and evaluation of humanized transgenic mice
      containing the beta(E) mutation in the context of the human beta-globin locus.
      Developmental expression of the human beta(E) locus transgene partially
      complements the hematological abnormalities in heterozygous knockout mice
      ((mu)beta(th-3/+)) and rescues the embryonic lethality of homozygous knockout
      mice ((mu)beta(th-3/th-3)). The phenotype of rescued mice was dependent on the
      transgene copy number. This mouse model displays hematological abnormalities
      similar to HbE/beta-thalassemia patients and represent an ideal in vivo model
      system for pathophysiological studies and evaluation of novel therapies.

PMID- 16631346
TI  - Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells
      overexpressing growth hormone.
AB  - In the present study, we report the upregulation of functional IGF-2Rs in cells
      overexpressing growth hormone (GH). EL4 lymphoma cells stably transfected with an
      rGH cDNA overexpression vector (GHo) exhibited an increase in the binding of
      (125)I-IGF-2 with no change in the binding affinity compared to vector alone
      controls. An increase in the expression of the insulin-like growth factor-2
      receptor (IGF-2R) in cells overexpressing GH was confirmed by Western blot
      analysis and IGF-2R promoter luciferase assays. EL4 cells produce insulin-like
      growth factor-2 (IGF-2) as detected by the reverse transcription-polymerase chain
      reaction (RT-PCR); however, no IGF-2 protein was detected by Western analysis.
      The increase in the expression of the IGF-2R resulted in greater levels of IGF-2
      uptake in GHo cells compared to vector alone controls. The data suggest that one
      of the consequences of the overexpression of GH is an increase in the expression
      of the IGF-2R.

PMID- 16631347
TI  - Murine taste-immune associative learning.
AB  - Taste-immune associative learning can result from contingent pairings of an
      immune-competent unconditioned stimulus (US) with a gustative conditioned
      stimulus (CS). Recalling such an association may induce a set of physiological
      responses affecting behavior, endocrine, and immune functions. We have
      established a model of behaviorally conditioned immunosuppression employing the
      immunosuppressant drug cyclosporine A (CsA) as the US and saccharin as the CS in
      rats and humans. In order to investigate the inter-species generalization of this
      neuro-immune interaction, we tested the feasibility of this paradigm in mice. In
      a single-bottle scheme, male BALB/c mice (n=5) were conditioned by conducting
      three association trials and a single recall trial. Control groups (n=5/group)
      were designed to assure associative learning, pharmacological effects of the US,
      and placebo effect. Results show that CsA-conditioned animals displayed
      significant immunosuppression in the spleen after recall, measured by in vitro T
      lymphocyte proliferation, and IL-2 production. However, the same animals did not
      show evidence of avoidance behavior to the CS. In contrast, evoking the
      association of saccharin-lithium chloride (inducing gastric malaise) in another
      set of animals (n=4/group) resulted in significant and pronounced avoidance of
      the taste (CS). These animals also displayed significant suppression of splenic T
      lymphocyte responsiveness after the recall phase. The present results indicate
      that mice seem to be capable of associating a gustative stimulus with CsA,
      resulting in behaviorally conditioned immunosuppression without affecting
      appetitive behavior.

PMID- 16631348
TI  - Long-term effects of athletics meet on the perceived competence of individuals
      with intellectual disabilities.
AB  - The purpose was to examine the effects of the type of athletic program
      (integrated versus segregated) and of the type of sport (basketball versus
      swimming) on two domains of perceived competence (athletic competence and social
      acceptance), and general self-worth. Participants were 48 adolescent females with
      intellectual disabilities (ID) divided equally into six groups: (a) segregated
      basketball, (b) integrated basketball, (c) segregated swimming, (d) integrated
      swimming, (e) physical education (PE), and (f) sedentary. The experimental
      treatment was 21 months long; for sport groups, this involved 2h of training each
      week and 12 competitive meets. We administrated Harter's (Harter, S. (1985).
      Manual for the self-perception profile for children. Denver: University of
      Denver) Self-Perception Profile for Children seven times to determine changes in
      perceived competence, and general self-worth. Results indicated: (a) no changes
      in perceived social acceptance; (b) significantly lower perceived athletic
      competence for the integrated groups; (c) significantly lower general self-worth
      for the basketball groups compared to the PE group. The integrated environment
      helps adolescents with ID to adopt a more realistic evaluation of their physical
      competence.

PMID- 16631349
TI  - Image registration and subtraction for the visualization of change in diabetic
      retinopathy screening.
AB  - Diabetic retinopathy (DR) is a leading cause of blindness in people of working
      age in developed countries. DR is characterized by lesions of the retinal
      microvasculature. This paper describes a technique for visualizing the changes
      which occur in retinal pathology over a 1 year interval. Pairs of retinal images
      of the same eye were acuired 12 months apart within a DR screening programme. The
      images were normalized, registered and subtracted to generate a contrast-enhanced
      difference image displaying changes in retinal appearance. The normalization
      factor and registration error were quantified for 104 pairs of retinal images.

PMID- 16631350
TI  - Inhibition of nNOS and COX-2 expression by lutein in acute retinal ischemia.
AB  - OBJECTIVE: Lutein is a major nutrient in the retina. Lutein has an antioxidative
      effect and protects against macular degeneration and retinal degenerative
      disease. However, the mechanism of lutein is not clear in retinal degeneration,
      and a role for lutein is not known in ischemic injury. In this study, an ischemia
      induced rat retina was examined to determine the effect of the lutein on ischemic
      retinal cell death. METHODS: We used a transient ischemia model of high
      intraocular pressure in the rat. Lutein (Kemin Foods, LC) was injected into the
      intraperitoneal or intravitreous before ischemia. Retinal degeneration was
      observed by light microscopy 24 h after ischemia. Expressions of neuronal nitric
      oxide synthase (nNOS) and cyclo-oxygenase-2 (COX-2) were detected by western blot
      analysis at various times after retinal ischemia. RESULTS: The nNOS and COX-2
      expression levels were increased early in ischemic control retinas, but these
      increases were inhibited by lutein. In addition, the inhibitory effect of lutein
      was observed to be dose dependent. Further, ischemia-induced cell death was
      inhibited by lutein. Lutein-injected ischemic retina appeared similar to normal
      retina. CONCLUSION: This study investigated the protective effect of lutein on
      retinal ischemia and the inhibitory effect of nNOS and COX-2 expressions. These
      results suggest that a supplement with lutein may have the potential to inhibit
      ischemic cell death by this mechanism in the neural retina.

PMID- 16631351
TI  - Dystrophic neuritic processes in epileptic cortex.
AB  - Cortical dysplasia is a frequent finding in cortical resections from children
      with refractory epilepsy. Diagnostic criteria and a classification scheme for
      cortical dysplasia has been proposed, though the relationship between specific
      cortical dysplasia features and their causal relationship with epilepsy is poorly
      understood. We reviewed 28 surgical resections from children and identified a
      common and easily recognized feature of cortical dysplasia: maloriented,
      misshapen and occasionally coarse neurofilament stained process forming a
      dystrophic neuritic background. The dystrophic neuritic background was associated
      with other features of cortical dysplasia in all 28 patients with cortical
      dysplasia, 26 with refractory epilepsy and 2 patients with other neurologic
      diagnoses. In seven children with refractory epilepsy due to other pathologic
      diagnosis such as vascular or glial lesions, the dystrophic neuritic background
      was only found in one patient with a ganglioglioma and other features suggestive
      of an associated cortical dysplasia. Our data indicate that a dystrophic neuritic
      background is a common and relatively specific neuropathologic finding in
      cortical dysplasia.

PMID- 16631352
TI  - No association between the brain-derived neurotrophic factor gene and
      schizophrenia in a Japanese population.
AB  - Brain-derived neurotrophic factor (BDNF) plays important roles in the survival,
      maintenance and growth of neurons. Several studies have indicated that BDNF is
      likely to be related to the pathogenesis of schizophrenia. Recent genetic
      analyses have revealed that BDNF gene polymorphisms are associated with
      schizophrenia, although contradictory negative findings have also been reported.
      To assess whether three BDNF gene polymorphisms (rs988748, C132T and rs6265)
      could be implicated in vulnerability to schizophrenia, we conducted a case
      control association analysis (349 patients and 423 controls) in Japanese
      subjects. We found no association between these BDNF gene polymorphisms and
      schizophrenia using both single-marker and haplotype analyses. The results of the
      present study suggest that these three BDNF gene polymorphisms do not play major
      roles in conferring susceptibility to schizophrenia in a Japanese population.
      However, further studies assessing the associations between these BDNF gene
      polymorphisms and schizophrenia should be performed in several other ethnic
      populations.

PMID- 16631353
TI  - The microcephaly ASPM gene and schizophrenia: A preliminary study.

PMID- 16631354
TI  - Long-term combination antipsychotic treatment in VA patients with schizophrenia.
AB  - Treatment guidelines consider antipsychotic monotherapy the standard of care for
      patients with schizophrenia. However, previous studies have reported widely
      varying, and sometimes high, rates of antipsychotic polypharmacy. We identified
      61,257 VA patients with schizophrenia in fiscal year 2000 who had >or=90 non
      institutionalized days and one or more fills of antipsychotic medications. We
      used criteria of increasing stringency (>or=30, >or=60, or >or=90 overlapping
      days' supply of antipsychotic medications) and several cross-sectional criteria
      from previous studies to compare the prevalence of antipsychotic polypharmacy
      using these definitions. We also describe specific treatment combinations among
      patients receiving long-term polypharmacy. The prevalence of antipsychotic
      polypharmacy was 20.0%, 13.1%, and 9.5% when defined by a >or=30, >or=60, or
      >or=90-day overlap, respectively. Cross-sectional definitions used in previous
      studies did not identify 32-89% of patients receiving long-term polypharmacy
      (>or=90 days). In addition, approximately half of patients identified by cross
      sectional criteria had only short-term overlaps of antipsychotic medications.
      Among patients receiving long-term polypharmacy, 74% received a first- and a
      second-generation agent, 18% received two second-generation agents, and 6%
      received two first-generation agents. Definitions of polypharmacy that rely on
      cross-sectional data or narrow observation periods do not accurately identify
      patients receiving long-term treatment; in this study, only 10% of patients with
      schizophrenia received combination treatments for >or=90 days. The most commonly
      used antipsychotic combinations have little support for safety or efficacy.
      Further research is needed to understand the impact of these treatments on
      symptoms, side effects, and costs.

PMID- 16631355
TI  - Reduction of dopamine-related transcription factors Nurr1 and NGFI-B in the
      prefrontal cortex in schizophrenia and bipolar disorders.
AB  - Abnormal cortical and subcortical dopaminergic activities are among the most
      consistent neuropathological findings in schizophrenia. The molecular mechanisms
      remain unspecified. NGFI-B and Nurr1 are two closely related transcription
      factors involved in dopaminergic cell differentiation, maturation, and apoptosis.
      NGFI-B knockout mice show attenuated behavioral response to dopamine receptor
      agonists, whereas Nurr1 knockout disrupts midbrain dopaminergic neuron
      development. To further understand the role of Nurr1 and NGFI-B in schizophrenia
      and bipolar disorders, we measured Nurr1 and NGFI-B mRNA in the prefrontal cortex
      Brodmann's areas 9 (BA 9) and BA 46 by in situ hybridization, and the protein
      levels in BA 9 by Western blotting, of patients with schizophrenia, major
      depression, and bipolar disorders, and non-psychiatric control subjects (n=15 per
      group). NGFI-B mRNA (P<0.05) and protein (P<0.01) were significantly lower in
      patients with schizophrenia (BA 9), and NGFI-B mRNA was lower in bipolar disorder
      (BA 9 and BA 46) than in the controls. In the deep cortical layers of BA 46,
      Nurr1 mRNA was significantly (P<0.05) lower in patients with bipolar disorder and
      schizophrenia than in the controls. Nurr1 protein in BA 9 was significantly lower
      in major depression (P<0.05) and lower at a trend level in schizophrenia
      (P=0.056) than in the controls. These data show a deficient prefrontal NGFI-B and
      Nurr1 expression in schizophrenia and bipolar disorder. Further study may
      elucidate if and how these deficiencies could be associated with abnormal
      dopaminergic functions seen in both illnesses.

PMID- 16631356
TI  - A comment on "Cognitive deficits in relatives of patients with schizophrenia: a
      meta-analysis" from a cognitive neuropsychological perspective.

PMID- 16631357
TI  - Lactobacilli binding human A-antigen expressed in intestinal mucosa.
AB  - Adherent lactic acid bacteria (LAB) in the human intestine were investigated
      using the surface plasmon resonance technique with the biosensor BIACORE-1000.
      Ninety-three LAB strains were isolated from human feces and evaluated for binding
      to human blood type-A antigen [GalNAcalpha1-3 (Fucalpha1-2) Gal-: A
      trisaccharide] expressed in the intestinal mucosa. Eleven strains showed strong
      adherence to an A-trisaccharide biotinyl polymer (BP) probe, and slightly or no
      adherence to a B-trisaccharide BP probe. Four strains with high adherence (high
      A/B ratio) were selected and their surface layer proteins (SLPs) were evaluated
      for A-antigen ligand binding using BIACORE. The SLP from L. brevis strain OLL2772
      showed a single band at ca. 48 kDa by SDS-PAGE analysis and it had a very strong
      adherence to the human A-antigen, as shown using an anti-A lectin blocking
      technique. A partial N-terminal sequence of the band showed strong homology to an
      S-layer protein of L. brevis ATCC8287T. The probiotic LAB binds to human blood
      type-A antigen expressed in the intestinal mucosa which may aid in colonization
      of the gut.

PMID- 16631358
TI  - Modification of formalin-induced nociception by different histamine receptor
      agonists and antagonists.
AB  - The present study evaluated the effects of different histamine receptor agonists
      and antagonists on the nociceptive response in the mouse formalin test.
      Intracerebroventricular (20-40 microg/mouse i.c.v.) or subcutaneous (1-10 mg/kg
      s.c.) injection of HTMT (H(1) receptor agonist) elicited a dose-related
      hyperalgesia in the early and late phases. Conversely, intraperitoneal (20 and 30
      mg/kg i.p.) injection of dexchlorpheniramine (H(1) receptor antagonist) was
      antinociceptive in both phases. At a dose ineffective per se, dexchlorpheniramine
      (10 mg/kg i.p.) antagonized the hyperalgesia induced by HTMT (40 mug/mouse i.c.v.
      or 10 mg/kg s.c.). Dimaprit (H(2) receptor agonist, 30 mg/kg i.p.) and ranitidine
      (H(2) receptor antagonist, 20 and 40 mg/kg i.p.) reduced the nociceptive
      responses in the early and late phases. No significant change in the
      antinociceptive activity was found following the combination of dimaprit (30
      mg/kg i.p.) with ranitidine (10 mg/kg i.p.). The antinociceptive effect of
      dimaprit (30 mg/kg i.p.) was prevented by naloxone (5 mg/kg i.p.) in the early
      phase or by imetit (H(3) receptor agonist, 25 mg/kg i.p.) in both early and late
      phases. The histamine H(3) receptor agonist imetit was hyperalgesic following
      i.p. administration of 50 mg/kg. Imetit-induced hyperalgesia was completely
      prevented by treatment with a dose ineffective per se of thioperamide (H(3)
      receptor antagonist, 5 mg/kg i.p.). The results suggest that histamine H(1) and
      H(3) receptor activations increase sensitivity to nociceptive stimulus in the
      formalin test.

PMID- 16631359
TI  - Monoclonal anti-mouse laminin antibodies: AL-1 reacts with laminin alpha1 chain,
      AL-2 with laminin beta1 chain, and AL-4 with the coiled-coil domain of laminin
      beta1 chain.
AB  - We analyzed the reactivity of three different commercially available rat
      monoclonal antibodies raised against mouse laminin-alpha1beta1gamma1 (laminin
      111), AL-1, AL-2, and AL-4. Using ELISA assays, Western blot analysis and
      immunostainings we present refined epitope maps for these three laminin
      monoclonals. AL-1 reacted, as predicted with laminin alpha1 chain. AL-4 has also
      been marketed as an alpha1 chain specific probe, but we show here that AL-4
      detects mouse laminin beta1 chain, in the distal part of the coiled-coil region.
      AL-2 was predicted to react with all three chains near the cross-region, but
      seems to primarily react with laminin beta1 chain.

PMID- 16631360
TI  - Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed
      diets containing t10, c12-, and c9, t11-conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA) isomers have unique effects on tissue lipids. Here
      we investigated the influence of individual CLA isomers on the lipid weight and
      fatty acid composition of lipid metabolizing (i.e. liver and retroperitoneal
      adipose) and lipid sensitive (i.e. spleen and heart) tissues. Female mice (8 week
      old; n=6/group) were fed either a control or one of the two CLA isomer
      supplemented (0.5%) diets for 8 weeks. The cis-9, trans-11-CLA diet reduced the
      18:1n-9 wt% by 20-50% in liver, adipose tissue, and spleen, reduced the spleen n
      3 polyunsaturated fatty acid (PUFA) by 90%, and increased the n-6 PUFA wt% by 20
      50% in all tissues except heart. The trans-10, cis-12-CLA reduced both the n-6
      and n-3 PUFA wt% in liver (>50%), reduced the heart n-3 PUFA wt% by 25%, and
      increased the wt% of spleen n-3 PUFA by 700%. The functional consequences of such
      changes in tissue fatty acid composition need to be investigated.

PMID- 16631361
TI  - The nuclear pore complex up close.
AB  - Transport between the nucleus and cytoplasm is mediated by nuclear pore complexes
      (NPCs), perforations in the double-membrane of the nuclear envelope. NPCs are
      huge protein assemblies made up of distinct subcomplexes. The complex modular
      nature of the NPC and limitations in the current experimental approaches render
      the analysis of NPCs and nucleocytoplasmic transport at the molecular level
      difficult. Recent efforts in the NPC/nucleocytoplasmic transport field have
      focused on elucidating the core components that make up NPC structure (or the
      lack thereof) and function. These include results obtained by more conventional
      methods, such as electron microscopy or biochemical strategies, as well as more
      advanced applications, such as X-ray crystallography and atomic force microscopy.

PMID- 16631362
TI  - DNA damage repair: anytime, anywhere?
AB  - Regulation of the DNA damage response is tightly connected to transcription and
      replication. These DNA transacting processes share common factors and use similar
      strategies to exert their function. However, unlike replication and
      transcription, DNA repair systems may be required anywhere, and at any time,
      whenever DNA damage occurs in the cell nucleus. This raises questions concerning
      the spatiotemporal organization of genome caretaking. Currently, quantitative
      live cell imaging techniques combined with methods to induce local DNA damage in
      a small region of the nucleus are contributing substantially to unravelling the
      molecular mechanisms underlying the cellular response to DNA damage.

PMID- 16631363
TI  - Current and emerging technologies for the study of bacteria in the outdoor air.
AB  - Pathogenic bacteria dispersed into the outdoor air from natural events or human
      activity are an important concern affecting public health, agriculture,
      ecological health and international security. Recent studies in atmospheric
      microbiology have contributed to our ability to detect bacterial pathogens in air
      samples, increased our knowledge of the spatial and temporal dispersal of
      aerosolized bacteria and furthered our understanding of the natural bacterial
      diversity and composition of air. Significant questions remain about bacterial
      dispersal and diversity in outdoor air that will benefit from continued
      technological advances. These include determining spatial and temporal patterns
      of aerosol dispersal, identifying the links between detection, concentration and
      viability of bacterial pathogens and disease incidence, and documenting the
      composition and regional movement of bacterial species in air.

PMID- 16631364
TI  - Characterization of various functional groups present in the capsule of
      Microcystis and study of their role in biosorption of Fe, Ni and Cr.
AB  - This study demonstrates highest biosorption of Fe followed by Ni and Cr by
      Microcystis in single, bi and trimetallic combination. Fe was not only
      preferentially adsorbed from the metal mixtures but Ni and Cr failed to decrease
      its biosorption. The agreement of the data of Fe biosorption with the Langmuir
      model suggested monolayer sorption and existence of constant sorption energy
      during the experimental conditions. In contrast to Fe biosorption, Ni and Cr
      sorption followed the Freundlich isotherm; this demonstrates a multilayer
      biosorption of the two metals. IR analysis of Microcystis cells confirmed the
      presence of a large number of -COO(-) and some amino groups in the Microcystis
      cell wall. The oxygen and nitrogen donor atoms from carboxyl and amino groups
      were found to play a vital role in metal biosorption by Microcystis cell walls,
      and ion exchange mechanisms were involved in the biosorption of test metals.
      Extra peaks present in Ni and Cr treated cells implied that amino groups are more
      responsible for Ni and Cr biosorption.

PMID- 16631365
TI  - Triplex forming ability of oligonucleotides containing 2'-O-methyl-2-thiouridine
      or 2-thiothymidine.
AB  - The triplex forming ability of oligonucleotides containing 2'-O-methyl-2
      thiouridine (s2Um) and 2-thiothymidine (s2T) was studied. The UV melting
      experiments revealed that triplex forming oligonucleotides (TFOs) containing both
      s2Um or s2T stabilized significantly parallel triplexes. The main reason for
      stabilization of triplexes was due to the stacking effect of the 2-thiocarbonyl
      group. Moreover, it turned out that these modified TFOs had a high selectivity in
      recognition of a matched Hoogsteen base from a mismatched one.

PMID- 16631366
TI  - Modulators of the human CCR5 receptor. Part 3: SAR of substituted 1-[3-(4
      methanesulfonylphenyl)-3-phenylpropyl]-piperidinyl phenylacetamides.
AB  - SAR and PK studies led to the identification of N-(1-{(3R)-3-(3,5-difluorophenyl)
      3-[4-methanesulfonylphenyl] propyl}piperidin-4-yl)-N-ethyl-2-[4
      methanesulfonylphenyl]acetamide as a highly potent and selective ligand for the
      human CCR5 chemokine receptor with good oral pharmacokinetic properties.

PMID- 16631367
TI  - Chronic inflammatory demyelinating polyneuropathy.
AB  - Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired
      neuropathy, presumably of immunological origin. Its clinical presentation and
      course are extremely variable. CIDP is one of the few peripheral neuropathies
      amenable to treatment. Typical cases associate progressive or relapsing-remitting
      motor and sensory deficit with increased CSF protein content and
      electrophysiological features of demyelination. In other instances the neuropathy
      is predominantly or exclusively motor or sensory, CSF normal and
      electrophysiological studies fail to show evidence of demyelination. In such
      cases conventional diagnostic criteria are not filled yet the patient may respond
      to immunomodulatory treatments. In this paper we review the diagnostic pitfalls
      and clinical variants of CIDP to illustrate the problems that may arise. The
      different therapeutic options are reviewed. Axon loss associated with
      demyelination is the most important factor of disability and resistance to
      treatment.

PMID- 16631368
TI  - Assessment of radionuclide arthrography in the evaluation of loosening of knee
      prostheses.
AB  - BACKGROUND: Radionuclide arthrography (RNA) is an established technique in the
      evaluation of hip prostheses but there is scant literature on its role in knee
      prostheses and no data specifically related to unicompartmental knee prostheses.
      We reviewed our experience with radionuclide arthrography in total (TKRs) and
      unicompartmental (UKRs) knee arthroplasties. METHODS: A retrospective review of
      66 consecutive RNA studies that either had direct surgical correlation or
      arthroscopic assessment in conjunction with at least 12 months of clinical and
      radiological follow-up. These formed the basis of our case note review. 26
      studies had a confirmed diagnosis of prosthetic loosening. RESULTS: By using
      standardised criteria for diagnosis and an early and late imaging protocol at 30
      min and 4 h, RNA had an overall sensitivity of 88% and a specificity of 88% for
      the diagnosis of prosthetic loosening. The individual sensitivities and
      specificities were 93% and 86% for TKRs and 82% and 92% for UKRs. The technique
      was unable to detect femoral component loosening unless a long femoral stem was
      present, although only 8% of episodes of prosthetic loosening did not involve the
      tibial component. CONCLUSION: Radionuclide arthrography should be considered as a
      useful diagnostic test for the evaluation of loosening of the tibial component of
      knee prostheses but requires early and late imaging and close attention to detail
      to achieve optimal results.

PMID- 16631369
TI  - Stanmore non-invasive growing arthrodesis endoprosthesis in the reconstruction of
      complicated total knee arthroplasty: A case report.
AB  - As the number of primary and revision arthroplasties performed each year
      increases, the complexity of the reconstructive efforts also increases. A case of
      a patient with a total knee arthroplasty complicated with infection, deficient
      extensor mechanism, bone loss and limb shortening of 5.5 cm is reported. We
      describe an alternative surgical technique of reconstruction of the knee and
      lengthening of the limb using the Stanmore Non-Invasive Growing-Distal Femoral
      Prosthesis. The prosthesis had a magnetic disc attached to a gearbox. The
      generation of an external electromagnetic field caused the magnetic disc to
      rotate and lengthen the prosthesis. This reconstructive technique has not been
      described in the literature.

PMID- 16631370
TI  - Three-bundle popliteus tendon: a nonsymptomatic anatomical variation.
AB  - A 34-year-old man suffering from knee pain on the medial side of his right knee
      underwent knee arthroscopy. The arthroscopy revealed the popliteus tendon with an
      appearance of three bundles. Three-bundle popliteus tendon is a normal variant
      finding with no clinical significance.

PMID- 16631371
TI  - Visualisation of tibiofemoral contact in total knee replacement using optical
      device.
AB  - An in situ optical visualization technique (OVT) has been developed to identify
      the tibiofemoral contact (TFC) area during prosthesis indentation. An artificial
      total knee replacement (TKR) with borosilicate glass femoral component has been
      reproduced similarly to the original one. The medial and lateral contact areas
      have been observed, located and measured by means of in situ OVT. Therefore, it
      was experimentally possible to ensure a good axial alignment of the femoral
      component and tibial polyethylene insert. In addition, experimental measurement
      for load-displacement curves became reproducible. Furthermore, the evolution of
      the medial and lateral TFC areas as a function of the normal load was
      established. Finally, this study has shown that the in situ OVT is a simple in
      vitro method that provides comparable results with well-known methods such as
      Fuji film technique.

PMID- 16631372
TI  - Synthesis and structure-activity relationship studies of 4,11-diaminonaphtho[2,3
      f]indole-5,10-diones.
AB  - We describe the synthesis of derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10
      dione and their cytotoxicity for human tumor cells that express major
      determinants of altered anticancer drug response, the efflux pump P-glycoprotein,
      and non-functional p53. Nucleophilic substitution of methoxy groups in 4,11
      dimethoxynaphtho[2,3-f]indole-5,10-dione with various ethylenediamines yielded
      the derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10-dione, the indole
      containing analogues of the antitumor agent ametantrone. The cytotoxicity of
      novel compounds for multidrug resistant, P-glycoprotein-expressing tumor cells is
      highly dependent on the N-substituent at the terminal amino group of the
      ethylenediamine moiety. Whereas p53 null colon carcinoma cells were less
      sensitive to the reference drug doxorubicin than their counterparts with wild
      type p53, the majority of novel naphthoindole derivatives were equally potent for
      both cell lines, regardless of the p53 status.

PMID- 16631373
TI  - Articular cartilage depicted at optimized angular position of Laue angular
      analyzer by X-ray dark-field imaging.
AB  - Using 36.0 keV X-ray from synchrotron radiation, we examined the optimized
      angular position of Laue analyzer for depicting articular cartilage of an intact
      human finger by X-ray dark-field imaging. The surface of articular cartilage was
      depicted clearly by adopting the offset angle of 0.04 arcsec to lower angular
      side to the analyzer whilst the contour of articular cartilage was delineated
      clearly at the other angular positions of the analyzer within the width of the
      rocking curve.

PMID- 16631374
TI  - Photoprotective properties of Prunella vulgaris and rosmarinic acid on human
      keratinocytes.
AB  - UVA radiation provokes the generation of reactive oxygen species (ROS), which
      induce oxidative stress in the exposed cells leading to extensive cellular damage
      and cell death either by apoptosis or necrosis. One approach to protecting human
      skin against the harmful effects of UV radiation is by using herbal compounds as
      photoprotectants. This study evaluated the protective effects of Prunella
      vulgaris L. (Labiatae) and its main phenolic acid component, rosmarinic acid
      (RA), against UVA-induced changes in a human keratinocyte cell line (HaCaT).
      Human keratinocytes exposed to UVA (10-30 J/cm(2)) were treated with an extract
      of P. vulgaris (1-75 mg/l) or RA (0.9-18 mg/l) for 4h. P. vulgaris and RA
      exhibited ability to reduce the UVA-caused decrease in a cell viability monitored
      by neutral red retention and by LDH release into medium. The P. vulgaris extract
      and RA significantly suppressed UVA-induced ROS production, which manifests as a
      decrease in intracellular lipid peroxidation, elevation of ATP and reduced
      glutathione. Post-treatment with P. vulgaris extract and RA also significantly
      reduced DNA damage. In addition, UVA-induced activation of caspase-3 was
      inhibited by treatment with P. vulgaris and RA. The P. vulgaris extract and RA
      demonstrated a concentration-dependent photoprotection (maximum at 25-50 mg/l and
      9 mg/l, respectively). These results suggest that P. vulgaris and RA, used in
      skin care cosmetics, may offer protection against UVA-induced oxidative stress
      and may be beneficial as a supplement in photoprotective dermatological
      preparations.

PMID- 16631375
TI  - Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated
      macrophages.
AB  - Patients with severe burn injuries are extremely susceptible to infection, and
      the host's antibacterial responses are frequently suppressed by alternatively
      activated macrophages (M2Mphi), commonly demonstrated in these patients. An
      immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral
      blood of thermally injured patients, has been described as an inducer of M2Mphi.
      In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mphi
      generation stimulated by PMN-II was examined. M2Mphi were generated from resident
      Mphi (R-Mphi, lower chamber) after cultivation with PMN-II (upper chamber) in a
      dual-chamber transwell. However, M2Mphi were not generated from R-Mphi when the
      same transwell cultures were performed in the presence of GL. M2Mphi were not
      generated from R-Mphi after cultivation with PMN-II previously treated with GL,
      while R-Mphi previously treated with GL converted to M2Mphi after they were
      cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II
      were shown to be effector molecules responsible for the generation of M2Mphi.
      However, these soluble factors were not produced by PMN-II treated with GL. These
      results indicate that GL inhibits PMN-II-stimulated M2Mphi generation through the
      inhibition of CCL2/interleukin-10 production by PMN-II.

PMID- 16631376
TI  - Improving mass accuracy of high performance liquid chromatography/electrospray
      ionization time-of-flight mass spectrometry of intact antibodies.
AB  - The glycosylation profile of intact antibody due to the galactose and fucose
      heterogeneity in the N-linked sugars was determined with instrument resolution of
      5000 and 10,000. After deconvolution of electrospray ionization mass spectra to
      complete convergence, several extra peaks appeared in addition to the peaks
      observed in the original mass spectra. The artificial peaks were avoided if
      deconvolution was stopped after a smaller number of iterations. A standard
      antibody was used as an external calibrant to minimize mass measurement errors
      during long-period experiments. Precision of four consecutive LC/MS measurements
      of the same antibody was 10 ppm (+/-1.5 Da). By using this approach, the masses
      of 11 intact antibodies were measured. All antibodies containing N-terminal
      glutamines had a negative mass shift due to the formation of pyroglutamate (-17
      Da). Although the pyroglutamate variant of intact antibody was not resolved from
      the unmodified variant, this modification led to a mass shift proportional to the
      percentage of N-terminal pyroglutamate. By accurately measuring the mass shift we
      were able to quantify the abundance of pyroglutamic acid on intact antibodies.
      Mass accuracy in measuring different antibodies was below 30 ppm (+/-4 Da). The
      accurate mass measurement can be an effective tool for monitoring chemical
      degradations in therapeutic antibodies.

PMID- 16631377
TI  - Local functions for FMRP in axon growth cone motility and activity-dependent
      regulation of filopodia and spine synapses.
AB  - Genetic deficiency of the mRNA binding protein FMRP results in the most common
      inherited form of mental retardation, Fragile X syndrome. We investigated the
      localization and function of FMRP during development of hippocampal neurons in
      culture. FMRP was distributed within granules that extended into developing axons
      and growth cones, detectable at distances over 300 microm from the cell body. In
      mature cultures, FMRP granules were present in both axons and dendrites, with
      pockets of higher concentrations appearing intermittently, along distal axon
      segments and near synapses. MAP1b mRNA, a known FMRP target, was also localized
      to axon growth cones. Morphometric analysis of growth cones from the FMR1 KO
      revealed both excess filopodia and reduced motility. At later stages during
      synapse formation, FMR1 KO neurons exhibited excessive filopodia and long spines
      along dendrites, yet there was a marked decrease in the density of spine-like
      protrusions juxtaposed to presynaptic terminals. In contrast, there was no
      difference in the density of shaft synapses between FMR1 KO and WT. Brief
      depolarization of WT neurons resulted in increased numbers of filopodia and spine
      synapses, whereas no additional morphologic changes were observable in dendrites
      of FMR1 KO neurons that already had increased density of filopodia-spines. These
      findings suggest that alterations in the regulation of axonal growth and
      innervation in FMR1 KO neurons may contribute to the dendritic and spine
      pathology in Fragile X syndrome. This work has broader implications for
      understanding the role of mRNA binding proteins in developmental and protein
      synthesis-dependent plasticity.

PMID- 16631378
TI  - Cloning, purification, and characterization of a non-collagenous anti-angiogenic
      protein domain from human alpha1 type IV collagen expressed in Sf9 cells.
AB  - alpha1(IV)NC1, a cleavage fragment of the carboxy terminal non-collagenous human
      alpha1 chain of type IV collagen, is derived from the extracellular matrix
      specifically by MMP-2. Recently we determined the in vitro and in vivo anti
      angiogenic activity of alpha1(IV)NC1 and presently, its role in cancer therapy is
      under evaluation. To characterize alpha1(IV)NC1 as a potential candidate for drug
      development and to test its efficacy in animal models, an effective method to
      produce a purified active form of alpha1(IV)NC1 is needed. In the present study,
      expression of alpha1(IV)NC1 in Sf9 cells using baculovirus expression system was
      discussed, this method was found to be effective in the production of a
      functionally active soluble form of the recombinant protein. The purified protein
      showed its characteristic activities such as inhibiting cell proliferation,
      migration, and tube formation in endothelial cells.

PMID- 16631379
TI  - Innate immune responses in rainbow trout (Oncorhynchus mykiss, Walbaum) induced
      by probiotics.
AB  - Carnobacterium maltaromaticum B26 and Carnobacterium divergens B33, which were
      isolated from the intestine of healthy rainbow trout (Oncorhynchus mykiss,
      Walbaum), were selected as being potentially useful as probiotics with
      effectiveness against Aeromonas salmonicida and Yersinia ruckeri. Thus, rainbow
      trout administered with feed supplemented with B26 or B33 dosed at >10(7) cells
      g(-1) feed conferred protection against challenge with virulent cultures of the
      pathogens. Moreover, both cultures persisted in the gut for up to 3 weeks after
      administration. The cultures enhanced the cellular and humoral immune responses.
      Specifically, fish fed with B26 demonstrated significantly increased phagocytic
      activity of the head kidney macrophages, whereas the use of B33 led to
      significant increases in respiratory burst and serum lysozyme activity. Also, the
      gut mucosal lysozyme activity for fish fed with both cultures was statistically
      higher than the controls.

PMID- 16631380
TI  - Cloning and organisation analysis of a hepcidin-like gene and cDNA from Japan sea
      bass, Lateolabrax japonicus.
AB  - A hepcidin gene was amplified from the liver of Lateolabrax japonicus challenged
      with a mixed bacterial suspension. Using RT-PCR and RACE, a full length cDNA
      sequence of the hepcidin like antimicrobial peptide was determined. The complete
      hepcidin cDNA Hepc2 is 581 bases and contains an ORF of 258 bases with a coding
      capacity of 86 amino acids. The deduced amino acid sequence, which shares eight
      cysteines at the identical conserved positions, and gene organisation are
      conserved between Japan sea bass and other fish species. The predicted molecular
      weight of the peptide is 9.4 kDa. The 3'-untranslated region is composed of 225
      bp with a polyadenylation signal AATAAA sequence appearing at 189 nt and the
      poly(A) tail at 212 nt downstream of stop codon TGA. The predicted signal peptide
      cleavage site of its deduced peptide is between codons 24 and 25. Japan sea bass
      hepcidin-like genomic DNA hepc2 sequence including upstream and downstream
      regions was composed of two introns and three exons. The cloned 173-bp upstream
      sequence of Japan sea bass hepcidin-like gene contains putative regulatory
      elements and several binding motifs for transcription factors. High homologies
      with hepcidin cDNAs and peptides of white bass (Morone chrysops), human and other
      fish were shown. Hepc2 of Lateolabrax japonicus is a new member of the hepcidin
      gene family.

PMID- 16631381
TI  - A cortical potential imaging study from simultaneous extra- and intracranial
      electrical recordings by means of the finite element method.
AB  - In the present study, we have validated the cortical potential imaging (CPI)
      technique for estimating cortical potentials from scalp EEG using simultaneously
      recorded electrocorticogram (ECoG) in the presence of strong local inhomogeneity,
      i.e., Silastic ECoG grid(s). The finite element method (FEM) was used to model
      the realistic postoperative head volume conductor, which includes the scalp,
      skull, cerebrospinal fluid (CSF) and brain, as well as the Silastic ECoG grid(s)
      implanted during the surgical evaluation in epilepsy patients, from the co
      registered magnetic resonance (MR) and computer tomography (CT) images. A series
      of computer simulations were conducted to evaluate the present FEM-based CPI
      technique and to assess the effect of the Silastic ECoG grid on the scalp EEG
      forward solutions. The present simulation results show that the Silastic ECoG
      grid has substantial influence on the scalp potential forward solution due to the
      distortion of current pathways in the presence of the extremely low conductive
      materials. On the other hand, its influence on the estimated cortical potential
      distribution is much less than that on the scalp potential distribution. With
      appropriate numerical modeling and inverse estimation techniques, we have
      demonstrated the feasibility of estimating the cortical potentials from the scalp
      EEG with the implanted Silastic ECoG gird(s), in both computer simulations and in
      human experimentation. In an epilepsy patient undergoing surgical evaluation, the
      cortical potentials were reconstructed from the simultaneously recorded scalp
      EEG, in which main features of spatial patterns during interictal spike were
      preserved and over 0.75 correlation coefficient value was obtained between the
      recorded and estimated cortical potentials. The FEM-based CPI technique provides
      a means of connecting the simultaneous recorded ECoG and the scalp EEG and
      promises to become an effective tool to evaluate and validate CPI techniques
      using clinic data.

PMID- 16631382
TI  - In vivo neuropathology of the hippocampal formation in AD: a radial mapping MR
      based study.
AB  - Early involvement of the hippocampal formation is the biological basis of the
      typical learning deficit in Alzheimer's disease (AD). However, the hippocampal
      formation is unevenly affected by AD pathology, deposits of plaques and tangles
      being particularly dense in the CA1 field and subiculum. The aim of the study was
      to locate in vivo the structural changes within the hippocampal formation in AD
      patients of mild to moderate severity. A group of 28 AD patients and 40
      cognitively intact persons (age 74 +/- 9 and 71 +/- 7 years) underwent T1
      weighted high-resolution MR scans. The hippocampal formation was isolated by
      manually tracing on 35 coronal slices the outlines of the hippocampus proper and
      subiculum after registration to a common stereotactic space. Group differences
      were assessed with algorithms developed ad hoc that make use of three-dimensional
      parametric surface mesh models. In AD patients, significant atrophic changes
      amounting to tissue loss of 20% or more were found in regions of the hippocampal
      formation corresponding to the CA1 field and part of the subiculum. Regions
      corresponding to the CA2-3 fields were remarkably spared. We conclude that the
      regions of the hippocampal formation that we found atrophic in AD patients are
      those known to be affected from pathological studies. This study supports the
      possibility of carrying out in vivo macroscopic neuropathology of the hippocampus
      with MR imaging in the neurodegenerative dementias.

PMID- 16631383
TI  - Eye closure in darkness animates olfactory and gustatory cortical areas.
AB  - In two previous fMRI studies, it was reported that eyes-open and eyes-closed
      conditions in darkness had differential effects on brain activity, and typical
      patterns of cortical activity were identified. Without external stimulation,
      ocular motor and attentional systems were activated when the eyes were open. On
      the contrary, the visual, somatosensory, vestibular, and auditory systems were
      activated when the eyes were closed. In this study, we investigated whether
      cortical areas related to the olfactory and gustatory system are also animated by
      eye closure without any other external stimulation. In a first fMRI experiment (n
      = 22), we identified cortical areas including the piriform cortex activated by
      olfactory stimulation. In a second experiment (n = 12) subjects lying in darkness
      in the MRI scanner alternately opened and closed their eyes. In accordance to
      previous studies, we found activation clusters bilaterally in visual,
      somatosensory, vestibular and auditory cortical areas for the contrast eyes
      closed vs. eyes-open. In addition, we were able to show that cortical areas
      related to the olfactory and gustatory system were also animated by eye closure.
      These results support the hypothesis that there are two different states of
      mental activity: with the eyes closed, an "interoceptive" state characterized by
      imagination and multisensory activity and with the eyes open, an "exteroceptive"
      state characterized by attention and ocular motor activity. Our study also
      suggests that the chosen baseline condition may have a considerable impact on
      activation patterns and on the interpretation of brain activation studies. This
      needs to be considered for studies of the olfactory and gustatory system.

PMID- 16631384
TI  - Clustered functional MRI of overt speech production.
AB  - To investigate the neural network of overt speech production, event-related fMRI
      was performed in 9 young healthy adult volunteers. A clustered image acquisition
      technique was chosen to minimize speech-related movement artifacts. Functional
      images were acquired during the production of oral movements and of speech of
      increasing complexity (isolated vowel as well as monosyllabic and trisyllabic
      utterances). This imaging technique and behavioral task enabled depiction of the
      articulo-phonologic network of speech production from the supplementary motor
      area at the cranial end to the red nucleus at the caudal end. Speaking a single
      vowel and performing simple oral movements involved very similar activation of
      the cortical and subcortical motor systems. More complex, polysyllabic utterances
      were associated with additional activation in the bilateral cerebellum,
      reflecting increased demand on speech motor control, and additional activation in
      the bilateral temporal cortex, reflecting the stronger involvement of phonologic
      processing.

PMID- 16631385
TI  - Evaluation of the GTRACT diffusion tensor tractography algorithm: a validation
      and reliability study.
AB  - Fiber tracking, based on diffusion tensor imaging (DTI), is the only approach
      available to non-invasively study the three-dimensional structure of white matter
      tracts. Two major obstacles to this technique are partial volume artifacts and
      tracking errors caused by image noise. In this paper, a novel fiber tracking
      algorithm called Guided Tensor Restore Anatomical Connectivity Tractography
      (GTRACT) is presented. This algorithm utilizes a multi-pass approach to fiber
      tracking. In the first pass, a 3D graph search algorithm is utilized. The second
      pass incorporates anatomical connectivity information generated in the first pass
      to guide the tracking in this stage. This approach improves the ability to
      reconstruct complex fiber paths as well as the tracking accuracy. Validation and
      reliability studies using this algorithm were performed on both synthetic phantom
      data and clinical human brain data. A method is also proposed for the evaluating
      reliability of fiber tract generation based both on the position of the fiber
      tracts, as well the anisotropy values along the path. The results demonstrate
      that the GTRACT algorithm is less sensitive to image noise and more capable of
      handling areas of complex fiber crossing, compared to conventional streamline
      methods.

PMID- 16631386
TI  - Very high frequency oscillations (VHFO) as a predictor of movement intentions.
AB  - Gamma band (30-80 Hz) oscillations arising in neuronal ensembles are thought to
      be a crucial component of the neural code. Recent studies in animals suggest a
      similar functional role for very high frequency oscillations (VHFO) in the range
      80-200 Hz. Since some intracerebral studies in humans link VHFO to
      epileptogenesis, it remains unclear if VHFO appear in the healthy human brain and
      if so which is their role. This study uses EEG recordings from twelve healthy
      volunteers, engaged in a visuo-motor reaction time task, to show that VHFO are
      not necessarily pathological but rather code information about upcoming
      movements. Oscillations within the range (30-200 Hz) occurring in the period
      between stimuli presentation and the fastest hand responses allow highly accurate
      (>96%) prediction of the laterality of the responding hand in single trials. Our
      results suggest that VHFO belong in functional terms to the gamma band that must
      be considerably enlarged to better understand the role of oscillatory activity in
      brain functioning. This study has therefore important implications for the
      recording and analysis of electrophysiological data in normal subjects and
      patients.

PMID- 16631387
TI  - A nuclear DNA phylogeny of the woolly mammoth (Mammuthus primigenius).

PMID- 16631388
TI  - Molecular systematics and phylogeography of the cryptic species complex Baetis
      rhodani (Ephemeroptera, Baetidae).
AB  - Genetic studies have highlighted cryptic diversity in many well-known taxa
      including aquatic insects, with the general implication that there are more
      species than are currently recognised. Baetis rhodani Pictet are among the most
      widespread, abundant and ecologically important of all European mayflies
      (Ephemeroptera), and used widely as biological indicators of stream quality.
      Traditional taxonomy and systematics have never fully resolved differences among
      suspected cryptic species in the B. rhodani complex because morphological
      characters alone do not allow reliable distinction. This is particularly true
      among larvae, the life-stage used most widely in monitoring. Here, we assess the
      molecular diversity of this complex in one of the largest such studies of cryptic
      species in the order Ephemeroptera to date. Phylogenies were constructed using
      data from the mitochondrial cytochrome oxidase subunit I (COI) gene. Two
      monophyletic groups were recovered consisting of one major haplogroup and a
      second clade of 6 smaller but distinct haplogroups. Haplogroup divergence ranged
      from 0.2-3% (within) to 8-19% (among) with the latter values surpassing maxima
      typically reported for other insects, and provides strong evidence for cryptic
      species in the B. rhodani complex. The taxonomic status of these seven
      haplogroups remains undefined. Their distributions across Western Europe reveal
      no obvious geographic pattern, suggesting widespread diffusion of genetic
      lineages since the last glacial maximum. The implications of these findings are
      far-reaching given the ecological and bioindicator significance of what now
      appears to be several taxa.

PMID- 16631389
TI  - A multidisciplinary approach reveals cryptic diversity in Western Palearctic
      Tetramorium ants (Hymenoptera: Formicidae).
AB  - Diversity of ants of the Tetramorium caespitum/impurum complex was investigated
      in a multidisciplinary study. Focusing on morphologically hardly distinguishable
      Western Palearctic samples, we demonstrate the genetic and phenotypic diversity,
      demarcate phylogenetic entities, and discuss the clades in terms of biogeography.
      Sequences of 1113bp of the mitochondrial COI gene revealed 13 lineages. COII
      data, worker morphometry and male genitalia morphology corroborated the COI
      results for seven lineages; the remaining six were disregarded because of small
      sample size. A comparison with published data on cuticular hydrocarbons showed
      correspondence. The seven entities show different distribution patterns, though
      some ranges overlap in Central Europe. Since no major discrepancy between the
      results of the different disciplines became apparent, we conclude that the seven
      entities within the T. caespitum/impurum complex represent seven species.
      Geographical evidence allows the identification of T. caespitum and T. impurum,
      and we therefore designate neotypes and redescribe the two species in terms of
      morphology and mtDNA. As the revision of about 50 taxon names would go beyond the
      scope of this study, we refer to the remaining five species under code names. We
      discuss our findings in terms of plesiomorphy and convergent evolution by
      visualizing the mtDNA phylogeny in morphological space.

PMID- 16631390
TI  - Nuclear markers reveal that inter-lake cichlids' similar morphologies do not
      reflect similar genealogy.
AB  - The apparent inter-lake morphological similarity among East African Great Lakes'
      cichlid species/genera has left evolutionary biologists asking whether such
      similarity is due to sharing of common ancestor or mere convergent evolution. In
      order to answer such question, we first used Geometric Morphometrics, GM, to
      quantify morphological similarity and then subsequently used Amplified Fragment
      Length Polymorphism, AFLP, to determine if similar morphologies imply shared
      ancestry or convergent evolution. GM revealed that not all presumed morphological
      similar pairs were indeed similar, and the dendrogram generated from AFLP data
      indicated distinct clusters corresponding to each lake and not inter-lake
      morphological similar pairs. Such results imply that the morphological similarity
      is due to convergent evolution and not shared ancestry. The congruency of GM and
      AFLP generated dendrograms imply that GM is capable of picking up phylogenetic
      signal, and thus GM can be potential tool in phylogenetic systematics.

PMID- 16631391
TI  - Factors derived from mouse embryonic stem cells promote self-renewal of goat
      embryonic stem-like cells.
AB  - Goat embryonic stem (ES)-like cells could be isolated from primary materials
      inner cell masses (ICMs) and remain undifferentiated for eight passages in a new
      culture system containing mouse ES cell conditioned medium (ESCCM) and on a
      feeder layer of mouse embryo fibroblasts (MEFs). However, when cultured in medium
      without mouse ESCCM, goat ES-like cells could not survive for more than three
      passages. In addition, no ES-like cells could be obtained when ICMs were cultured
      on goat embryo fibroblasts or the primary materials-whole goat blastocysts were
      cultured on MEFs. Goat ES-like cells isolated from ICMs had a normal karyotype
      and highly expressed alkaline phosphatase. Multiple differentiation potency of
      the ES-like cells was confirmed by differentiation into neural cells and
      fibroblast-like cells in vitro. These results suggest that mouse ES cells might
      secrete factors playing important roles in promoting goat ES-like cells' self
      renewal, moreover, the feeder layers and primary materials could also influence
      the successful isolation of goat ES-like cells.

PMID- 16631392
TI  - Complementary and lateralized forms of processing in Bufo marinus for novel and
      familiar prey.
AB  - Amphibian vision is one of the most comprehensively studied of all vertebrate
      sensory systems. However, the processes of object recognition and memory in
      anuran amphibians have resisted satisfactory explanation. Our research shows that
      insight to the issue of visual discrimination and recognition in toads may be
      gained by investigation of the specialized and complementary functions carried
      out by the left and right brain hemispheres. We report that specialized processes
      associated with the left eye (right hemisphere) of the Bufo marinus toad carry
      out decisions to view and strike at complex prey stimuli recognized as 'novel.'
      This was demonstrated in the toads' preferences when provided a choice between
      identical novel insect models presented simultaneously into the left and right
      lateral, monocular visual fields. In a second experiment, videotaped trials of
      toad groups competing in an open field for live crickets were analysed for
      lateralized prey-catching behaviour. Concomitant with a preference for directing
      agonistic strikes at conspecifics within the left visual hemifield, toads were
      found to possess a significant preference for directing predatory responses at
      the familiar prey viewed in the right visual hemifield. The preference for
      directing prey-catching responses at freely moving crickets in the right visual
      hemifield supports the earlier findings drawn from automated and familiar model
      insect prey. We present a hypothesis explaining differences in hemispheric
      processing in toads responding to 'novel' and 'familiar' prey types, utilizing a
      range of long-term memories found to be lateralized in other vertebrates.

PMID- 16631393
TI  - The effect of perioperative beta-blockade on the pulmonary function of patients
      undergoing major arterial surgery.
AB  - INTRODUCTION: Concern about the potential detrimental side-effects of beta
      blockade on pulmonary function often dissuades against their perioperative use in
      patients undergoing major arterial surgery (especially in those with chronic
      obstructive pulmonary disease (COPD)). In this study we aimed to establish
      prospectively the clinical relevance of these concerns. METHODS: After ethics
      committee approval and individual informed consent, the pulmonary function of
      twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to
      undergo non-emergency major vascular surgery was studied by recording symptoms
      and spirometry before and after institution of effective beta-blockade. Fifteen
      patients (75%) had significant smoking histories (mean pack years/patient=50),
      while 12 (60%) had COPD. RESULTS: All patients tolerated effective beta-blockade
      satisfactorily without developing either subjective deterioration in symptoms or
      significant change on spirometry. The mean change in FEV1 following adequate beta
      blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean
      percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). CONCLUSIONS:
      Previously held concerns about worsening pulmonary function through the short
      term use of beta-blockers should not dissuade their perioperative usage in
      patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary
      function tests in preoperative assessment and risk stratification also appears
      unaffected by this therapy.

PMID- 16631394
TI  - Managing risk factors for atherosclerosis in critical limb ischaemia.
AB  - OBJECTIVE: To review the best medical management of critical limb ischaemia
      (CLI). METHODS: Published studies dealing with CLI and risk factors were searched
      for via PUBMED. FINDINGS AND CONCLUSIONS: Patients with critical limb ischaemia
      (CLI) have a one and ten year mortality of approximately 20% and 75%
      respectively. Risk factors for the development of peripheral atherosclerosis are
      the same as for coronary and cerebrovascular atherosclerosis namely diabetes
      mellitus, hyperlipidaemia, arterial hypertension, and smoking. As there are few
      studies of risk factor for peripheral arterial occlusive disease (PAOD),
      treatment recommendations are often based on studies in patients with coronary or
      cerebrovascular atherosclerosis. While waiting for specific studies, CLI patients
      should be treated according to current guidelines for other atherosclerotic
      patients.

PMID- 16631395
TI  - Blood cells as targets of snake toxins.
AB  - Snake venoms are mixtures of enzymes and peptides which exert toxicological
      effects by targeting their substrates or receptors upon envenomation. Snake venom
      proteins widely affect vascular system including circulating blood cells,
      coagulation factors, and vascular wall components. Many of the toxic proteins
      have multiple targets. For example, some metalloproteinase domain-containing
      snake venom protein cleaves not only fibrinogen but also receptors on platelets.
      Also, it is frequent that toxins from different snake venom protein families are
      capable of binding to a common target on cells. Most of the cytotoxic effects in
      the venom are usually results of the activities of metalloproteinase, C-type
      lectin, disintegrin, cysteine-rich protein, as well as phospholipase A(2). There
      has been a growing interest in studying the structure and function of these snake
      venom proteins because many of them have high structural homologies to proteins
      found in human. Therefore, the understanding of how these toxins interact with
      their targets may contribute to the discovery of novel physiological processes
      and the development of therapeutic agents for cardiovascular diseases. In this
      review, we summarize how snake toxins target blood cells with an emphasis on
      their effects on platelet function.

PMID- 16631397
TI  - New insights into the cell cycle profile of Paracoccidioides brasiliensis.
AB  - The present work focuses on the analysis of cell cycle progression of
      Paracoccidioides brasiliensis yeast cells under different environmental
      conditions. We optimized a flow cytometric technique for cell cycle profile
      analysis based on high resolution measurements of nuclear DNA. Exponentially
      growing cells in poor-defined or rich-complex nutritional environments showed an
      increased percentage of daughter cells in accordance with the fungus' multiple
      budding and high growth rate. During the stationary growth-phase cell cycle
      progression in rich-complex medium was characterized by an accumulation of cells
      with higher DNA content or pseudohyphae-like structures, whereas in poor-defined
      medium arrested cells mainly displayed two DNA contents. Furthermore, the
      fungicide benomyl induced an arrest of the cell cycle with accumulation of cells
      presenting high and varying DNA contents, consistent with this fungus' unique
      pattern of cellular division. Altogether, our findings seem to indicate that P.
      brasiliensis may possess alternative control mechanisms during cell growth to
      manage multiple budding and its multinucleate nature.

PMID- 16631398
TI  - Population genetic analysis of Phialocephala fortinii s.l. and Acephala applanata
      in two undisturbed forests in Switzerland and evidence for new cryptic species.
AB  - The genetic structure of the root endophytes Phialocephala fortinii s.l. and
      Acephala applanata was analyzed in two undisturbed forests. A total of 606
      strains isolated from surface-sterilized, fine roots of Picea abies and Vaccinium
      myrtillus were examined. Two new cryptic species of P. fortinii were recognized
      and host specialization of A. applanata was confirmed. This species was almost
      exclusively isolated from roots of P. abies. The index of association did not
      deviate significantly from zero within any population, suggesting that
      recombination occurs or had occurred. Significant gene but no genotype flow was
      detected among study sites for P. fortinii s.l. In contrast, several isolates of
      A. applanata with both identical multi-locus haplotype and identical ISSR
      fingerprint were found in both study sites indicating genotype flow or a recent
      common history.

PMID- 16631399
TI  - Olfactory sensory input increases gill ventilation in male round gobies
      (Neogobius melanostomus) during exposure to steroids.
AB  - In teleostean fish, ventilation increases have been observed in response to low
      dissolved oxygen levels, visual stimuli, and gustatory cues. However, olfactory
      sensory input may also stimulate gill ventilation rate. We investigated whether
      olfactory sensory input mediates gill ventilation responses, as suggested by the
      observation that steroidal compounds detected by the olfactory system elicited
      increases in opercular activity in the perciform teleost, the round goby
      (Neogobius melanostomus). Close parallels between gill ventilation and olfactory
      responses, led us to conduct an empirical study that used two different olfactory
      sensory deprivation techniques to seek a causal relationship between olfactory
      epithelial activity and hyperventilation. Chemical lesion of olfactory sensory
      neurons or mechanical occlusion of the nasal cavities inhibited gill ventilation
      responses of reproductive male round gobies to estrone (1,3,5(10)-estratrien-3-ol
      17-one) and to ovarian extracts. This direct evidence demonstrates the role of
      olfactory sensory input for the gill ventilation response to putative
      reproductive pheromones and may represent an important regulatory mechanism for
      odorant sampling during pheromone communication.

PMID- 16631400
TI  - Isolation, cloning and sequencing of transferrins from red-eared turtle, African
      ostrich, and turkey.
AB  - Transferrins form an important class of iron-binding proteins widely distributed
      in the physiological fluids of vertebrates and invertebrates. In vertebrates they
      are present mostly in serum as serotransferrins. In birds and reptiles
      transferrins are also found in eggs as ovotransferrins. However, until now only
      chicken and duck ovotransferrin sequences have been published. This paper
      presents data on the purification, biochemical analysis, cloning and sequencing
      of ovotransferrins from red-eared turtle, African ostrich and turkey, revealing
      their significant homology with other known ovotransferrin sequences. The
      proteins were purified by size-exclusion and anion-exchange chromatography.
      Isoelectric points, iron-saturated and iron-free spectra, as well as the mRNA
      nucleotide sequences of 2,409 nt (ORF: 2,106 nt encoding a 701-amino-acid
      polypeptide; ), 2,418 nt (ORF 2,118 nt encoding a 705-amino-acid polypeptide; ),
      and 2,397 nt (ORF: 2,118 nt encoding a 705-amino-acid polypeptide; ) were
      determined for ostrich (OtrF), red-eared turtle (TtrF), and turkey (MtrF)
      ovotransferrin, respectively.

PMID- 16631401
TI  - Androgen insufficiency in women.
AB  - Androgens are directly secreted by the ovaries and adrenals in women, and
      androgen precursors from these glands are converted in a variety of peripheral
      tissues into androgens. The major androgen in women is testosterone, and its
      action in target tissues can be mediated through the androgen receptor or through
      the estrogen receptor after aromatization to estradiol. Low sexual desire that
      causes personal distress (or hypoactive sexual desire disorder [HSDD]) is the
      most common form of female sexual dysfunction, and androgen insufficiency is one
      cause of this problem. In addition to a low libido, the clinical construct of the
      female androgen insufficiency syndrome includes the presence of persistent,
      unexplained fatigue and a decreased sense of well-being. Although there is
      conflicting information about the relationship between serum testosterone
      concentrations and sexual desire, multiple randomized, double-blind, placebo
      controlled treatment trials have demonstrated that testosterone improves libido
      significantly more than placebo. Doses that provide physiologic to slightly
      supraphysiologic serum free or bioavailable testosterone concentrations are safe
      and associated with only mild androgenic side effects of acne and hirsutism.
      Oral, but not parenteral or transdermal, testosterone may decrease high-density
      lipoprotein cholesterol. At present, no testosterone preparation has been
      approved by the FDA for the treatment of low sexual desire (HSDD), so all such
      therapy is considered to be off-label use at this time.

PMID- 16631402
TI  - Determination of confidence intervals of metabolic fluxes estimated from stable
      isotope measurements.
AB  - Metabolic fluxes, estimated from stable isotope studies, provide a key to
      quantifying physiology in fields ranging from metabolic engineering to the
      analysis of human metabolic diseases. A serious drawback of the flux estimation
      method in current use is that it does not produce confidence limits for the
      estimated fluxes. Without this information it is difficult to interpret flux
      results and expand the physiological significance of flux studies. To address
      this shortcoming we derived analytical expressions of flux sensitivities with
      respect to isotope measurements and measurement errors. These tools allow the
      determination of local statistical properties of fluxes and relative importance
      of measurements. Furthermore, we developed an efficient algorithm to determine
      accurate flux confidence intervals and demonstrated that confidence intervals
      obtained with this method closely approximate true flux uncertainty. In contrast,
      confidence intervals approximated from local estimates of standard deviations are
      inappropriate due to inherent system nonlinearities. We applied these methods to
      analyze the statistical significance and confidence of estimated gluconeogenesis
      fluxes from human studies with [U-13C]glucose as tracer and found true limits for
      flux estimation in specific human isotopic protocols.

PMID- 16631404
TI  - Septic arthritis with no organism: a dilemma.

PMID- 16631405
TI  - Alkaline sphingomyelinase: an old enzyme with novel implications.
AB  - Alkaline sphingomyelinase (alk-SMase) is present in the intestinal tract and
      additionally human bile. It hydrolyses sphingomyelin in both intestinal lumen and
      the mucosal membrane in a specific bile salt dependent manner. The enzyme was
      discovered 36 years ago but got real attention only in the last decade, when
      sphingomyelin metabolism was realized to be a source of multiple lipid
      messengers, and when dietary sphingomyelin was found to inhibit colonic
      tumorigenesis in animals. The enzyme shares no structural similarity with other
      SMases and belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
      The enzyme is of specific properties, such as bile salt dependency, trypsin
      resistance, high stability, and tissue specific expression. In the colon, the
      enzyme may play antiproliferative and antiinflammatory roles through generating
      ceramide, reducing the formation of lysophosphatidic acid, and inactivating
      platelet-activating factor. The enzyme is down regulated in human long-standing
      ulcerative colitis and colonic adenocarcinoma, and mutation of the enzyme has
      been found in colon cancer cells. In the small intestine, alk-SMase is the key
      enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect
      the cholesterol uptake and have impact on sphingomyelin levels in plasma
      lipoproteins. The review summarizes the new information of alk-SMase from
      biochemical, cell and molecular biological studies in the last decade and
      evaluates its potential implications in development of colon cancer, inflammatory
      bowel diseases, and atherosclerosis.

PMID- 16631406
TI  - Nerve excitability testing and its clinical application to neuromuscular
      diseases.
AB  - Non-invasive nerve excitability testing measures the membrane polarization, ion
      channel function and paranodal/internodal condition of peripheral nerves. This
      technique has been recently used for various neuromuscular disorders, such as
      pure motor conduction block in multifocal motor neuropathy, conduction block in
      carpal tunnel syndrome and Na(+) channel function disorders in diabetic
      neuropathy, to shed light on their pathophysiology. Here, we review the basics of
      ion channel functions and membrane properties that influence nerve excitability,
      the basic principles of nerve excitability testing and the reported findings in
      various disorders.

PMID- 16631407
TI  - Dangerous entanglements.
AB  - The promise of stem-cell therapy is long-term repair of damaged organs by
      transplantation. Inoculum size might be a determinant of successful repair, and
      efforts are being made to improve conditions for ex vivo expansion of stem cells
      prior to transplantation. A recent article by Damelin and colleagues raised
      concerns about this approach, demonstrating that stem cells lack the decatenation
      G2 checkpoint that preserves genetic stability. Cells that fail to disentangle
      chromatids prior to mitosis are prone to the types of chromosomal aberrations
      that are observed in cancer cells. Ex vivo expansion of stem cells might have the
      unintended consequence of encouraging malignant progression.

PMID- 16631408
TI  - Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis
      caused by type II collagen in the mouse.
AB  - Recently, glycogen synthase kinase-3 (GSK-3) has being identified as an
      ubiquitous serine-threonine protein kinase that participates in a multitude of
      cellular processes and plays an important role in the pathophysiology of a number
      of diseases. The aim of this study was to investigate the effects of GSK-3beta
      inhibition on the degree of arthritis caused by type II collagen (CII) in the
      mouse (collagen-induced arthritis; CIA). Mice developed erosive hind paw
      arthritis when immunized with CII in an emulsion in complete Freund's adjuvant
      (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice and the
      severity of CIA progressed over a 35-day period with radiographic evaluation
      revealing focal resorption of bone. The histopathology of CIA included erosion of
      the cartilage at the joint margins. Treatment of mice with the GSK-3beta
      inhibitor TDZD-8 (1 mg/kg/day i.p.) starting at the onset of arthritis (day 25)
      ameliorated the clinical signs at days 26-35 and improved histological status in
      the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly(ADP
      ribose) (PAR), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX
      2) revealed a positive staining in inflamed joints from mice subjected to CIA.
      The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 was significantly
      reduced in CII-challenged mice treated with the GSK-3beta inhibitor. Plasma
      levels of tumor necrosis factor (TNF)-alpha and the joint tissue levels of
      macrophage inflammatory protein (MIP)-1alpha and MIP-2 were also significantly
      reduced by GSK-3beta inhibition. These data demonstrate that GSK-3beta inhibition
      exerts an anti-inflammatory effect during chronic inflammation and is able to
      ameliorate the tissue damage associated with CIA.

PMID- 16631409
TI  - ELISpot assay as a sensitive tool to detect cellular immunity following influenza
      vaccination in kidney transplant recipients.
AB  - Enhanced cellular immunity following influenza vaccination has been undetectable
      in kidney transplant recipients so far. Protection from influenza is dependent on
      cellular and humoral immunity. Aim of the study was to investigate immune
      responses before and after vaccination with influenza A and B antigens in 65
      kidney transplant recipients. A significant increase in proliferative responses
      was only observed towards influenza B (P < 0.0001) by lymphocyte transformation
      test. The enzyme-linked immunospot (ELISpot) assay was more sensitive and
      detected significant, 3- to 5-fold increases (P < 0.0001) in interferon-gamma
      secretion using influenza A and B antigens. Furthermore, influenza antibody
      titers increased significantly (P < 0.0001). At month 1 post-vaccination 85% of
      patients displayed specific cellular, and 95% or 92% humoral immunity against
      influenza A and B, respectively. Thus, applying the sensitive ELISpot assay,
      influenza-specific cellular immunity could be detected for the first time in
      kidney transplant recipients after vaccination.

PMID- 16631411
TI  - The uterine junctional zone.
AB  - Magnetic resonance imaging has revealed that the endometrio-myometrial interface
      constitutes a distinct, hormone-dependent uterine compartment termed the
      junctional zone. In the non-pregnant uterus, highly specialized contraction waves
      originate exclusively from the junctional zone and participate in the regulation
      of diverse reproductive events, such as sperm transport, embryo implantation, and
      menstrual shedding. Conversely, growing evidence suggests that disruption of the
      normal endometrio-myometrial interface plays an integral role in diverse
      reproductive disorders. This chapter reviews our current understanding of the
      mechanisms that govern the cyclic changes in the uterine junctional zone and
      summarizes the evidence implicating the endometrio-myometrial interface in normal
      uterine physiology and pathological processes.

PMID- 16631412
TI  - Inadvertent germline transmission of AAV2 vector: findings in a rabbit model
      correlate with those in a human clinical trial.
AB  - The risk of germline transmission of vector sequences in humans is a major safety
      concern, because the enrollment of subjects of reproductive age in early-phase
      clinical trials of gene transfer continues to increase. In a study of adult men
      with hemophilia B, adeno-associated virus serotype 2 (AAV2) delivered to the
      liver via the hepatic artery resulted in unexpected transient vector
      dissemination to the semen. Here we report that intravenous AAV2 injection in
      rabbits proved a useful model to assess biologic parameters of vector
      dissemination to the semen. Detectable vector sequences in semen disappeared in a
      dose-dependent and time-dependent fashion. AAV infectious particles were present
      only as long as day 4 after injection and were undetectable thereafter. The
      kinetics of vector clearance was faster in the semen fractions enriched for
      motile sperm than in the total semen. In addition, increased frequency of semen
      sampling accelerated the clearance of vector sequences from semen. Long-term
      follow-up, spanning hundreds of spermatogenesis cycles, showed that there was no
      recurrence of detectable vector sequences in semen, thus reducing the probability
      of inadvertent transduction of early spermatogonia not committed to
      differentiation at the time of vector injection. We conclude that AAV2 presents
      minimal germline transmission risk for humans.

PMID- 16631413
TI  - Efficient transduction and engraftment of G-CSF-mobilized peripheral blood CD34+
      cells in nonhuman primates using GALV-pseudotyped gammaretroviral vectors.
AB  - The optimal stem cell source for stem cell gene therapy has yet to be determined.
      Most large-animal studies have utilized peripheral blood or marrow-derived cells
      collected after administration of granulocyte colony-stimulating factor (G-SCF)
      and stem cell factor (SCF); however, SCF is unavailable for clinical use in the
      United States and the European Union. A recent study in a competitive
      repopulation assay in the rhesus macaque showed very inefficient marking of G-CSF
      mobilized (G/only) peripheral blood (G-PBSC) CD34(+) cells relative to G-CSF and
      SCF-mobilized cells using vectors with an amphotropic pseudotype. Because G-PBSC
      would be the preferred target cell population for most clinical stem cell gene
      therapy applications, we asked whether we could achieve efficient transduction
      and engraftment of G-PBSC using Phoenix-GALV-pseudotyped vectors. We transplanted
      three baboons with G/only mobilized CD34(+) cells transduced with GALV
      pseudotyped retroviral vectors. We observed high-level, persistent engraftment of
      gene-modified G-PBSC in all animals with gene marking levels in granulocytes up
      to 60%. We analyzed amphotropic (PIT2) and GALV (PIT1) receptor expression in
      G/only cells and found preferential expression of PIT1 after G/only, which may
      explain the inferior results with amphotropic pseudotypes. These findings
      demonstrate that high stem cell gene transfer levels can be achieved using G-CSF
      mobilized PBSC with Phoenix-GALV-pseudotyped vectors.

PMID- 16631414
TI  - Pharmacokinetics of morphine in fish: winter flounder (Pseudopleuronectes
      americanus) and seawater-acclimated rainbow trout (Oncorhynchus mykiss).
AB  - We made a single intraperitoneal (IP) injection of morphine sulfate (40 mg/kg)
      into winter flounder and seawater acclimated rainbow trout at 10 degrees C and
      then followed its disposition by measuring the change in plasma morphine
      concentration for 100 h using a morphine specific ELISA. Disposition also was
      followed for 6h after a single IV injection of 7.5mg morphine sulfate in winter
      flounder. Plasma morphine reached a maximum within an hour post-injection IP and
      then decreased in a bi-exponential fashion with a rapid distribution phase
      followed by a slower elimination phase. The disposition was slower in flounder
      than in trout even though the fish were held at the same temperature. For
      example, plasma clearance was 76 mL h(-)(1) kg(-)(1) in the flounder but was
      almost twice as much in the trout (153 mL h(-)(1) kg(-)(1)) and mean residence
      time was 27.9h in the flounder but was 7.0 h in the trout. The present study is
      the first comprehensive pharmacokinetic analysis for any analgesic in an
      ectotherm, and our results show that: 1) significant intra-specific variation
      exists between fishes: and 2) the disposition of morphine in fish is
      approximately one order of magnitude slower than it is in mammals. These
      differences may be due in part to mass specific differences in cardiac output.

PMID- 16631415
TI  - Health care resource utilization in inflammatory bowel disease.
AB  - BACKGROUND & AIMS: The aim of this study was to quantify temporal changes in
      health care utilization by a population-based cohort of IBD. METHODS: By using
      the University of Manitoba IBD Epidemiology Database we assessed utilization of
      outpatient and hospital services, estimating relative risk (RR) of utilization
      for IBD cases compared with a matched cohort of non-IBD controls and for CD
      versus UC. We tested differences in utilization between prevalence cohorts 1990
      1991 and 2000-2001. Also, utilization of the 1987-1988 incidence cohort was
      followed forward 15 years from diagnosis. The probability, intensity, and volume
      of utilization were estimated. RESULTS: In 2000-2001, IBD patients compared with
      controls were more likely to have an outpatient visit (RR, 1.18; 95% confidence
      interval [CI], 1.17-1.19) and an overnight hospital stay (RR, 2.32; 95% CI, 2.16
      2.49). CD cases were more likely than UC cases to be hospitalized (RR, 1.26; 95%
      CI, 1.11-1.43) and had a greater number of outpatient visits. From 1990-1991 to
      2000-2001, IBD cases experienced a significant decrease in the likelihood of an
      outpatient surgical visit relative to non-IBD controls (P < .05), and for those
      cases who were hospitalized, CD cases tended to be less likely than UC cases to
      experience IBD-specific inpatient surgery (P < .07). Of the 1987-1988 incidence
      cohort, 80% of admissions that occurred during the follow-up period were during
      the first 5 years after diagnosis. CONCLUSIONS: In 2000-2001, health care
      utilization continued to be higher in IBD versus controls and CD versus UC;
      however, the gap in costly service utilization appeared to narrow between the
      latter pair.

PMID- 16631416
TI  - Teashirt 3 expression in the chick embryo reveals a remarkable association with
      tendon development.
AB  - Drosophila teashirt (tsh) is involved in the patterning of the trunk identity
      together with the Hox genes. In addition, it is also a player in the Wingless and
      the Hedgehog pathways. In birds and mammals, three Tshz genes are identified and
      the expression patterns for mouse Tshz1 and Tshz2 have been reported during
      embryogenesis. Recently, we showed that all three mouse Tshz genes can rescue the
      Drosophila tsh loss-of-function phenotype, indicating that the function of the
      teashirt genes has been conserved during evolution. Here we describe the
      expression pattern of chick TSHZ3 during embryogenesis. Chick TSHZ3 is expressed
      in several tissues including mesodermal derivatives, the central and peripheral
      nervous systems. Emphasis is laid on the dynamic expression occurring in regions
      of the somites and limbs where tendons develop. We show that TSHZ3 is activated
      in the somites by FGF8, a known inducer of the tendon marker SCX.

PMID- 16631417
TI  - Expression of Lrrn1 marks the prospective site of the zona limitans thalami in
      the early embryonic chicken diencephalon.
AB  - An unknown chicken gene selected from a published substractive hybridization
      screen (GenBank Accession No. ; [Christiansen, J.H., Coles, E.G., Robinson, V.,
      Pasini, A., Wilkinson, D.G., 2001. Screening from a subtracted embryonic chick
      hindbrain cDNA library: identification of genes expressed during hindbrain,
      midbrain and cranial neural crest development. Mech. Dev. 102, 119-133.]) was
      deemed of interest because of its dynamic pattern of expression across the
      forebrain and midbrain regions. A 528bp fragment cloned from early chick embryo
      cDNA and used for in situ hybridization corresponded to part of the 3'
      untranslated region of the chicken gene Leucine-rich repeat neuronal protein 1
      (Lrrn1). The expression of this gene, mapped in the embryonic chick brain between
      stages HH10 and HH26, apparently preconfigures the zona limitans thalami site
      before overt formation of this boundary structure. Apart of colateral expression
      in the forebrain, midbrain and hindbrain basal plate, the most significant
      expression of Lrrn1 was found early on across the entire alar plate of midbrain
      and forebrain (HH10). This unitary domain soon divides at HH14 into a rostral
      part, across alar secondary prosencephalon and prospective alar prosomere 3
      (prethalamus; caudal limit at the prospective zona limitans), and a caudal part
      in alar prosomere 1 (pretectum) and midbrain. The rostral forebrain domain later
      downregulates gradually most extratelencephalic signal of Lrrn1, but the rostral
      shell of zona limitans retains expression longer. Expression in the caudal alar
      domain also changes by downregulation within its pretectal subdomain. Caudally,
      the midbrain domain ends at the isthmo-mesencephalic junction throughout the
      studied period. Embryonic Lrrn1 signal also appears in the somites and in the
      otic vesicle.

PMID- 16631418
TI  - Quantification of uric acid, xanthine and hypoxanthine in human serum by HPLC for
      pharmacodynamic studies.
AB  - A simple HPLC method was developed and validated for the determination of uric
      acid (UA), xanthine (X) and hypoxanthine (HX) concentrations in human serum to
      support pharmacodynamic (PD) studies of a novel xanthine oxidase inhibitor during
      its clinical development. Serum proteins were removed by ultrafiltration. The
      hydrophilic analytes and the I.S. were eluted by 100% aqueous phosphate buffer
      mobile phase. The hydrophobic matrix components (late peaks) were eluted with a
      step gradient of a higher organic mobile phase. Validation on linearity,
      sensitivity, precision, accuracy, stability, and robustness of the method for PD
      biomarkers (UA, X, and HX) was carried out in a similar manner to that for
      pharmacokinetic (PK) data where applicable. Issues of selectivity for endogenous
      biomarker analytes and individual concentration variations were addressed during
      method validation. Standards were prepared in analyte-free phosphate buffer.
      Quality control samples were prepared in control serum from individuals not dosed
      with the xanthine oxidase inhibitor. The method was simple and robust with good
      accuracy and precision for the measurement of serum UA, X, and HX concentrations.

PMID- 16631419
TI  - Binding mode of novel 1-substituted quinazoline derivatives to poly(ADP-ribose)
      polymerase-catalytic domain, revealed by X-ray crystal structure analysis of
      complexes.
AB  - In order to clarify the role of the 1-substituent of quinazoline derivatives in
      their inhibitory activity against poly(ADP-ribose) polymerase (PARP), two novel
      inhibitors, 1 [8-hydroxy-1-(3-morpholinopropyl)-quinazoline-2,4(1H,3H)-dione] and
      2 [8-hydroxy-1-(3-phenoxypropyl)-quinazoline-2,4(1H,3H)-dione], were synthesized
      and subjected to X-ray crystal analysis in complex with the PARP C-terminal
      catalytic domain (PARP-CD), which requires NAD+ coenzyme for biological function.
      The nicotinamide-mimicking part of the quinazoline skeleton of 1 and 2 were both
      located at the nicotinamide subsite of the NAD+-binding pocket in the same manner
      as previously reported inhibitors: three hydrogen bonds [(Gly-863)NH-O12, (Gly
      863)O-HN3 and (Ser-904)O(gamma)-O12] and stacking interaction between the Tyr-907
      phenol and the quinazoline ring. On the other hand, the N-morpholinoprop-3-yl
      moiety introduced at the 1-position of the quinazoline ring in 1 bridged the
      large gap between the donor site and the acceptor site through a (Met-890)NH
      O20(morpholine) hydrogen bond, where the donor and the acceptor sites are
      classified as the binding sites of NAD+ and the ADP moiety of the poly(ADP
      ribose) chain, respectively. In contrast, the N-phenoxyprop-3-yl moiety in 2
      formed hydrophobic interactions close to the adenosine-binding site of NAD+,
      unlike the hydrogen bond such as in 1. As the inhibitory activities of 1 and 2
      for PARP were much more potent than those of the unsubstituted nicotinamide
      analogues, these results suggest that the occupation of the proximal region of
      the ADP phosphate-and adenosine-binding subsite of the donor site or that of the
      gap between the donor and the acceptor site by the 1-substituent of quinazoline
      may increase the inhibitory activity considerably. The nearly equal inhibitory
      activities of 1 and 2, despite of their different binding modes at the active
      site, indicate that this 1-substituent is promising in improving the
      bioavailability of the inhibitor without compromising its inhibitory activity.

PMID- 16631420
TI  - Probing the mechanism of purine nucleoside phosphorylase by steady-state kinetic
      studies and ligand binding characterization determined by fluorimetric
      titrations.
AB  - Reversible reaction catalyzed by trimeric purine nucleoside phosphorylase (PNP)
      from Cellulomonas sp. with typical and non-typical substrates, including product
      inhibition patterns of both reaction directions, and interactions of the enzyme
      with bisubstrate analogue inhibitors, were investigated by the steady-state
      kinetic methods and fluorimetric titrations. The ligand chromophores exist most
      probably as neutral species, and not N(1)-H monoanions, in the complex with PNP,
      as shown by determination of inhibition constants vs. pH. This supports the
      mechanism in which hydrogen bond interaction of N(1)-H with Glu204 is crucial in
      the catalytic process. Stoichiometry of ligand binding, with possible exception
      of hypoxanthine, is three molecules per enzyme trimer. Kinetic experiments show
      that in principle the Michaelis-Menten model could not properly describe the
      reaction. However, this model seems to hold for certain experimental conditions.
      Data presented here are supported by earlier findings obtained by means of
      fluorimetric titrations and protective effects of ligands on thermal inactivation
      of the enzyme. All results are consistent with the following mechanism for
      trimeric PNPs: (i) random binding of substrates, (ii) potent binding and slow
      release of some reaction products leading to the circumstances that the chemical
      step is not the slowest one and that rapid-equilibrium assumptions do not hold,
      (iii) a dual role of phosphate--a substrate and also a reaction modifier.

PMID- 16631421
TI  - Characterization of the microtubule proteome during post-diapause development of
      Artemia franciscana.
AB  - The microtubule proteome encompasses tubulin and a diverse group of proteins
      which associate with tubulin upon microtubule formation. These proteins either
      determine microtubule organization and function or their activity is influenced
      by microtubule association. To characterize the microtubule proteome in Artemia
      franciscana, tubulin assembly was induced with taxol in vitro after 0 and 12 h of
      post-diapause development. Proteins obtained by extraction of microtubules with
      0.5 M NaCl were electrophoresed in two-dimensional gels and analyzed by mass
      spectrometry. Fifty-five proteins were identified with 10 of these occurring at
      both developmental stages, and multiple isoforms were observed for some proteins
      of the Artemia proteome. Their functions include roles in membrane transport,
      metabolism, chaperoning and protein synthesis, thus reflecting physiological
      properties of encysted Artemia such as stress resistance and the ability to
      rapidly initiate post-diapause development. For example, chaperones may protect
      tubulin during encystment and facilitate folding in metabolically active embryos.
      Additionally, the interaction of metabolic enzymes with microtubules funnels
      reaction intermediates, potentially enhancing efficiency within biochemical
      processes. This study represents the first systematic characterization of a
      crustacean microtubule proteome. Although it is difficult to be certain that all
      protein associations documented herein occur in vivo, the results suggest how
      protein-protein interactions contribute to cytoplasmic organization while
      implying how Artemia embryos resist stress and remain capable of development once
      diapause terminates.

PMID- 16631422
TI  - Hepatotoxicity and antiretroviral therapy with protease inhibitors: A review.
AB  - Highly active antiretroviral therapy including protease inhibitors has led to
      dramatic decrease in the morbidity and mortality resulting from infection with
      human immunodeficiency virus-1. However, this combination regimen can be
      associated with the occurrence of serious toxicities, which may reduce patient
      compliance. In particular, human immunodeficiency virus-1 protease inhibitors and
      nevirapine among nonnucleoside reverse transcriptase inhibitors, have the
      potential for producing hepatotoxicity. We summarise current knowledge of the
      hepatotoxic effects associated with the commercially available human
      immunodeficiency virus-1 protease inhibitors based on a literature review of the
      major retrospective and prospective clinical studies designed to elucidate risk
      factors for developing hepatotoxicity among human immunodeficiency virus-1
      infected patients receiving antiretroviral therapy containing protease
      inhibitors. Coinfection with chronic hepatitis, a common occurrence in human
      immunodeficiency virus-1-infected patients, is identified as an independent risk
      factor for developing hepatotoxicity in antiretroviral-treated human
      immunodeficiency virus-1-infected patients treated with antiretroviral regimens
      containing protease inhibitors. The importance of other risk factors for
      developing protease inhibitor-associated hepatotoxicity and the mechanism
      underlying the drug-related hepatotoxicity are discussed. The data indicate that
      the potential for producing hepatotoxicity is variable among the protease
      inhibitors and suggest that based on differences in drug-related hepatotoxicity,
      certain protease inhibitors may be preferred for the treatment of human
      immunodeficiency virus-hepatitis C virus coinfected patients.

PMID- 16631423
TI  - Cost-effectiveness of different diagnostic strategies to assess gastro
      oesophageal reflux disease in patients with unexplained chronic persistent cough
      in Italy.
AB  - BACKGROUND: Chronic persistent cough is a common and disabling disorder and
      gastro-oesophageal reflux disease is considered to be the third leading cause,
      after asthma and postnasal drip. Therefore, patients with unexplained chronic
      persistent cough usually undergo a stepwise evaluation to establish the existence
      of a reflux disease. AIM: To identify the most cost-effective diagnostic approach
      to assess gastro-oesophageal reflux disease in patients with unexplained chronic
      persistent cough. METHODS: Direct and indirect costs associated with six
      diagnostic strategies using 24-h oesophageal pH-metry, oesophago
      gastroduodenoscopy and the proton pump inhibitors test in different sequences,
      were evaluated using a decision tree model. If the first test was positive, the
      diagnostic work-up was stopped, if negative the patient proceeded to the second
      test, and so on. Clinical data from an observational prospective trial conducted
      in 51 patients with unexplained chronic persistent cough were used in the
      economic model. RESULTS: All six strategies had the same clinical effectiveness
      (78.4%). The diagnostic work-up with the lowest cost was the proton pump
      inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a
      total cost of euro 211.08 (direct euro 142.93, indirect euro 68.15). CONCLUSIONS:
      This study shows that the lowest cost is the strategy where proton pump
      inhibitors test is performed as first investigation. Implementation of this
      diagnostic work-up may lead to cost savings in the management of patients with
      chronic persistent cough.

PMID- 16631424
TI  - Association of APOE-C1 gene cluster polymorphisms with gallstone disease.
AB  - BACKGROUND: Genetic polymorphisms in apolipoprotein genes may be associated with
      alteration in lipid profile and susceptibility to gallstone disease. AIM: To find
      out the association of APOE HhaI and APOC1 HpaI polymorphisms with gallstone
      disease. SUBJECTS: HhaI polymorphism of APOE and HpaI polymorphism of APOC1 were
      analysed in DNA samples of 214 gallstone patients and 322 age- and sex-matched
      healthy controls. METHODS: For genotyping DNA samples of all study subjects were
      amplified using polymerase chain reaction, followed by restriction digestion. All
      statistical analyses were done using SPSS v11.5 and ARLEQUIN v2.0 softwares.
      RESULT: APOC1 HpaI polymorphism was found to be significantly associated with
      gallstone disease. Frequency of H2H2 was significantly higher (P = 0.017) in
      patients than in controls and it was imposing very high risk (OR 9.416, 95% CI
      1.125-78.786) for gallstone disease. When data were stratified in male and
      female, H2H2 was associated (P = 0.011) with disease in females only. Analysis at
      allele level revealed no association. APOE HhaI polymorphism and APOE-C1
      haplotypes showed no association with gallstone disease. CONCLUSION: APOC1 HpaI
      polymorphism is associated with gallstone disease and shows gender-specific
      differences. APOE HhaI polymorphism may not be associated with gallstone disease.

PMID- 16631425
TI  - Influence of 17beta-estradiol and insulin on type II collagen and protein
      synthesis of articular chondrocytes.
AB  - Clinical observations have suggested a relationship between osteoarthritis and a
      changed estrogen metabolism in menopausal women. Type II collagen is one main
      structural protein of articular cartilage matrix and its synthesis is increased
      by insulin in growth plate cartilage. Therefore, it was investigated if [(3)H]
      proline incorporation and type II collagen synthesis (immunocytochemistry, ELISA)
      in female bovine articular chondrocytes are affected by 17beta-estradiol and/or
      insulin. Articular chondrocytes were cultured in monolayers at 5% O(2) in medium
      containing serum for 5-9 days, followed by application of 10(-13) to 10(-9) M
      estradiol or 5 microg/ml insulin during a serum-free culture phase of 2-3 days.
      Immunostaining for type II collagen was strong in the serum-free culture phase
      whereas it was negative for type I collagen, indicating that cells did not
      dedifferentiate to fibroblast-like cells during culture in serum-free medium.
      Whereas insulin raised the proline incorporation and the type II collagen
      synthesis significantly, physiological doses of estradiol did not show
      significant effects. The stimulating effect of insulin on the [(3)H]-proline
      incorporation or the type II collagen synthesis was significantly suppressed
      after preincubation of cells with 10(-11) to 10(-9) M estradiol resembling an
      unfavorable effect for articular cartilage. The suppression was reversed if cells
      were incubated with 10(-11) to 10(-7) M tamoxifen or ICI 182,780 combined with
      10(-11) or 10(-9) M estradiol followed by incubation with 5 microg/ml insulin,
      indicating an estrogen receptor-mediated process. Because the articular cartilage
      of diabetic patients is biomechanically less stable, further experiments are
      needed to clarify the role of estradiol and insulin in the metabolism of
      articular chondrocytes.

PMID- 16631426
TI  - Functionally improved bone in calbindin-D28k knockout mice.
AB  - In vitro studies indicate that Calbindin-D28k, a calcium binding protein, is
      important in regulating the life span of osteoblasts as well as the
      mineralization of bone extracellular matrix. The recent creation of a Calbindin
      D28k knockout mouse has provided the opportunity to study the physiological
      effects of the Calbindin-D28k protein on bone remodeling in vivo. In this
      experiment, histomorphometry, microCT, and bend testing were used to characterize
      bones in Calbindin-D28k KO (knockout) mice. The femora of Calbindin-D28k KO mice
      had significantly increased cortical bone volume (60.4% +/- 3.1) compared to wild
      type (WT) mice (45.4% +/- 4.6). The increased bone volume was due to a decrease
      in marrow cavity area, and significantly decreased endosteal perimeters (3.397 mm
      +/- 0.278 in Calbindin-D28k KO mice, and 4.046 mm +/- 0.450 in WT mice). Similar
      changes were noted in the analysis of the tibias in both mice. The bone formation
      rates were similar in the femoral and tibial cortical bones of both mice. microCT
      analysis of the trabecular bone in the tibial plateau indicated that Calbindin
      D28k KO mice had an increased bone volume (35.2% +/- 3.1) compared to WT mice
      (24.7% +/- 4.9) which was primarily due to increased trabecular number (8.99 mm(
      1) +/- 0.94 in Calbindin-D28k KO mice compared to 6.75 mm(-1) +/- 0.85 in WT
      mice). Bone mineral content analysis of the tibias indicated that there is no
      difference in the calcium or phosphorus content between the Calbindin-D28k KO and
      WT mice. Cantilever bend testing of the femora demonstrated significantly lower
      strains in the bones of Calbindin-D28k KO mice (4135 micro strain/kg +/- 1266)
      compared to WT mice (6973 micro strain/kg +/- 998) indicating that the KO mice
      had stiffer bones. Three-point bending demonstrated increased failure loads in
      bones of Calbindin-D28k KO mice (31.6 N +/- 2.1) compared to WT mice (15.0 N +/-
      1.7). In conclusion, Calbindin-D28k KO mice had increased bone volume and
      stiffness indicating that Calbindin-D28k plays an important role in bone
      remodeling.

PMID- 16631427
TI  - A functional polymorphism in MMP-9 is associated with childhood atopic asthma.
AB  - Although MMP-9 has been suggested to be important in inflammation and in the
      connective tissue remodeling associated with asthma, the genetic influences of
      the polymorphisms of MMP-9 are unclear. To examine whether polymorphisms in MMP-9
      are associated with childhood atopic asthma, we identified a total of 17
      polymorphisms and conducted an association study with asthma (n = 290) and
      controls (n = 638). 2127G>T and 5546G>A (R668Q) were significantly associated
      with the risk of childhood atopic asthma (p = 0.0032 and 0.0016, respectively).
      In haplotype analysis, we also found a positive association with a haplotype (p =
      0.0053). MMP-9 was expressed in cultured human bronchial epithelial cells, and
      the mRNA expression level was upregulated by dsRNA. Furthermore, the promoter SNP
      -1590C>T, in strong linkage disequilibrium with 2127G>T, enhanced the
      transcriptional level of MMP-9. Thus, the MMP-9 gene might be involved in the
      development of asthma through functional genetic polymorphisms.

PMID- 16631428
TI  - Abalone nacre insoluble matrix induces growth of flat and oriented aragonite
      crystals.
AB  - Mollusc shell formation takes place in a preformed extracellular matrix, composed
      of insoluble chitin, coated with proteins and dissolved macromolecules. The water
      soluble matrix is known to have a strong influence on the growth of CaCO(3),
      whereas the role of the insoluble matrix on mineralization is unclear. Therefore,
      we mineralized the EDTA (ethylenediaminetetraacetic acid) insoluble organic
      matrix of abalone nacre with a modified double-diffusion set-up, where the
      diffusing solutions were constantly renewed. Control experiments were performed
      with cellulose and chitosan foils. The mineralized matrices/foils were analyzed
      with SEM. We show that the insoluble matrix of abalone nacre induces the growth
      of flat and roughly polygonal CaCO(3) crystals. In some of the experiments with
      the insoluble matrix, the growth of three-dimensional parallel sheets of densely
      packed platelets inside the insoluble matrix was observed. XRD on these samples
      revealed that they consist of oriented aragonite.

PMID- 16631429
TI  - The interrelation of birth weight and regional lipid deposition: a twins study.
AB  - This study examined the hypothesis that low birth weight is associated with
      changes in regional lipid deposition as well as insulin sensitivity in adult
      twins. Eleven adult female twin pairs were studied by magnetic resonance to
      determine regional adiposity. Their insulin sensitivity was assessed by the
      homeostasis model assessment. There were significant associations between birth
      weight and current homeostasis model assessment value (r=-0.528, P=.012),
      abdominal visceral (r=-0.581, P=.005), and subcutaneous fat volumes (r=-0.638,
      P=.001) if the group of 22 subjects were analyzed as individuals. There were no
      significant associations of the intratwin pair difference in birth weight and
      differences between adult twins in these same variables possibly because of
      limited patient numbers. Reduced birth weight does confer an increased risk of
      abdominal adiposity as well as insulin resistance in twin populations as it does
      in the general population.

PMID- 16631430
TI  - Impact of sex-specific body composition on cardiovascular risk factors: the Hong
      Kong Cardiovascular Risk Factor Study.
AB  - The aim of the study was to analyze the effects of sex-specific distribution of
      adiposity, particularly emphasizing the independent contribution of waist and hip
      circumferences relative to body mass index (BMI), on cardiovascular risk factors
      in a Chinese population. Blood pressure and anthropometric and biochemical
      parameters were measured in 2510 population-based Chinese subjects. The relative
      contributions of waist and hip circumferences to the presence of cardiovascular
      risk factors were determined. The Chinese men were significantly larger than
      women, with greater BMI and central adiposity. Waist and hip circumferences were
      both positively associated with the presence of hypertension, dyslipidemia, and
      diabetes. However, after adjustment for BMI and age, hip circumference exhibited
      a significant dose-dependent inverse relationship with dyslipidemia and diabetes
      in women, but not men. Sex-specific differences exist. After adjustment for age
      and BMI, hip circumferences independently and inversely contribute to
      cardiovascular risk in women, but not in men. Increasing adjusted waist
      circumference was associated with increased risk of hypertension and diabetes in
      Chinese and dyslipidemia in women only.

PMID- 16631431
TI  - Liquid carbohydrate/essential amino acid ingestion during a short-term bout of
      resistance exercise suppresses myofibrillar protein degradation.
AB  - A number of physiological events including the level of contractile activity,
      nutrient status, and hormonal action influence the magnitude of exercise-induced
      skeletal muscle growth. However, it is not the independent action of a single
      mechanism, but the complex interaction between events that enhance the long-term
      adaptations to resistance training. The purpose of the present investigation was
      to examine the influence of liquid carbohydrate (CHO) and essential amino acid
      (EAA) ingestion during resistance exercise and modification of the immediate
      hormonal response on myofibrillar protein degradation as assessed by 3
      methylhistidine (3-MH) excretion. After a 4-hour fast, 32 untrained young men (18
      29 years) performed a single bout of resistance exercise (complete body; 3
      setsx10 repetitions at 75% of 1-repetition maximum; 1-minute rest between sets),
      during which they consumed a 6% CHO (n=8) solution, a 6-g EAA (n=8) mixture, a
      combined CHO+EAA (n=8) supplement, or placebo (PLA; n=8) beverage. Resistance
      exercise performed in conjunction with CHO and CHO+EAA ingestion resulted in
      significantly elevated (P<.001) glucose and insulin concentrations above
      baseline, whereas EAA ingestion only increased the postexercise insulin response
      (P<.05). Time matched at 60 minutes, the PLA group exhibited a peak cortisol
      increase of 105% (P<.001) with no significant change in glucose or insulin
      concentrations. Conversely, the CHO and CHO+EAA groups displayed a decrease in
      cortisol levels of 11% and 7%, respectively. Coinciding with these hormonal
      response patterns were significant differences in myofibrillar protein
      degradation. Ingestion of the EAA and CHO treatments attenuated 3-MH excretion 48
      hours after the exercise bout. Moreover, this response was synergistically
      potentiated when the 2 treatments were combined, with CHO+EAA ingestion resulting
      in a 27% reduction (P<.01) in 3-MH excretion. In contrast, the PLA group
      displayed a 56% increase (P<.01) in 3-MH excretion. These data demonstrate that
      not only does CHO and EAA ingestion during the exercise bout suppress exercise
      induced cortisol release; the stimulatory effect of resistance exercise on
      myofibrillar protein degradation can be attenuated, most dramatically when the
      treatments are combined (CHO+EAA). Through an "anticatabolic effect," this
      altered balance may better favor the conservation of myofibrillar protein.

PMID- 16631432
TI  - The effects of uncoupling protein 3 haplotypes on obesity phenotypes and very low
      energy diet-induced changes among overweight Korean female subjects.
AB  - Responses to energy restriction tend to vary within the population because of
      genetic differences. In this study, we have genotyped 6 uncoupling protein 3 (UCP
      3) polymorphisms (-55C/T, Int2-143G/C, Tyr99Tyr, Int3-47G/A, Int4-498C/T, and
      Tyr210Tyr) among 214 overweight Korean female subjects recruited from an obesity
      clinic. Three major haplotypes, identified with frequencies in excess of 0.04,
      were constructed from 6 single nucleotide polymorphisms. Association studies were
      then undertaken, involving the measurement of anthropometric characteristics and
      body composition both before and after 1 month of a energy-restriction regimen.
      At baseline, haplotype 1 (ht1) [CGTACC] was associated with elevated
      anthropometric characteristics, including body weight, waist-hip ratio, and body
      mass index, as well as body components, including body fat mass and body fat-free
      mass. After the completion of the 1-month weight control program, which involved
      a very low-energy (2900 kJ/d) diet, we analyzed the outcomes according to the UCP
      3 genetic polymorphisms. Among the 3 principal haplotypes, ht1 [CGTACC] was
      significantly associated with an increased reduction in body weight, in the
      codominant (P=.022), dominant (P=.016), and recessive (P=.041) models. Body mass
      index reduction was associated with the ht1 haplotype in a similar fashion. Among
      the body components, changes in body fat mass were significantly associated with
      ht1 [CGTACC] (P=.028), but changes in body fat-free mass were not significantly
      associated with the UCP-3 polymorphism.

PMID- 16631433
TI  - The association of plasma adiponectin level with carotid arterial stiffness.
AB  - Adiponectin plays important roles in protecting against both insulin resistance
      and the development of atherosclerosis. The aim of the present study was to
      investigate the clinical impact of plasma adiponectin on arterial stiffness, a
      functional property of atherosclerosis, in type 2 diabetic and nondiabetic
      subjects. We evaluated plasma adiponectin levels and stiffness index beta for the
      common carotid artery assessed by ultrasound using a phase-locked echo-tracking
      system for 98 type 2 diabetic subjects and 116 nondiabetic subjects as controls.
      Plasma adiponectin levels were significantly lower in the diabetic than in the
      nondiabetic group. The stiffness index beta was significantly higher in the
      diabetic than in the nondiabetic group. Plasma adiponectin level was
      significantly correlated with stiffness index beta in the group of all subjects
      (r=-0.189, P=.006) and the nondiabetic group (r=-0.187, P=.045), but not in the
      diabetic group (r=0.045, P=.665). On multiple regression analysis, plasma
      adiponectin level was found to be a significant independent contributor to
      stiffness index beta in the group of all subjects (beta=-0.232, P=.020) and the
      nondiabetic group (beta=-0.337, P=.016), but not in the diabetic group. In
      conclusion, adiponectin is significantly but weakly associated with carotid
      arterial stiffness independently of known atherogenic factors in the nondiabetic
      group and that of all subjects, although no significant association between these
      variables was found in the group of diabetic subjects.

PMID- 16631434
TI  - Multiple defects in counterregulation of hypoglycemia in modestly advanced type 2
      diabetes mellitus.
AB  - In type 2 diabetes mellitus (T2DM), little is known about hormonal responses to
      hypoglycemia. In particular, beta-cell responses to hypoglycemia have not been
      carefully investigated and potentially because of confounding factors or
      insufficient power, conflicting data have been obtained regarding growth hormone
      responses. We therefore compared hormonal responses including rates of insulin
      secretion during a 2-hour hyperinsulinemic hypoglycemic clamp in a relatively
      large number of nondiabetic (n=21) and moderately insulin-deficient subjects with
      T2DM (homeostasis model assessment of beta-cell function [HOMA-%B], 751+/-160 vs
      1144+/-83 [pmol/L]/[mmol/L], P<.04) (n=14) matched for age, sex, and body mass
      index. Subjects with T2DM were excluded for antecedent hypoglycemia, and baseline
      glycemia was controlled by a variable infusion of insulin overnight. Although
      both groups of subjects had indistinguishable plasma glucose levels at baseline
      and virtually identical levels of plasma insulin and glucose throughout the
      hypoglycemic clamp, insulin secretion decreased more slowly in the subjects with
      T2DM. The time required for insulin secretion to decline to half its baseline
      level was markedly increased (38.9+/-4.9 vs 22.3+/-1.3 minutes [SD], P<.01), and
      insulin secretion decreased to a lesser extent (-0.79+/-0.17 vs -1.51+/-0.09
      [pmol/L]/kg per minute, P<.002). Moreover, responses of glucagon (28.3+/-7.3 vs
      52.8+/-7.0 ng/L, P<.05) and growth hormone (2.9+/-0.8 vs 6.3+/-0.9 ng/mL, P<.04)
      were reduced in the subjects with T2DM, whereas responses of epinephrine,
      norepinephrine, and cortisol were similar to those in nondiabetic subjects (all
      P>0.6). We conclude that multiple defects exist in hormonal responses to
      hypoglycemia in T2DM with moderate beta-cell failure. These include delayed and
      reduced decreases in insulin secretion, and impaired increases of plasma glucagon
      and growth hormone.

PMID- 16631435
TI  - Effect of ezetimibe on low-density lipoprotein subtype distribution: results of a
      placebo-controlled, double-blind trial in patients treated by regular low-density
      lipoprotein apheresis and statins.
AB  - Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to
      lower low-density lipoprotein (LDL) cholesterol. We have previously shown that
      ezetimibe can decrease LDL cholesterol by 16% even in patients treated by regular
      LDL apheresis and statins (Atherosclerosis. 2005;180:107-112). However, it is
      unclear whether ezetimibe decreases all LDL subfractions equally in patients with
      hypercholesterolemia. We therefore evaluated the effect of ezetimibe (5 weeks, 10
      mg/d) on LDL subtype distribution in a placebo-controlled, double-blind
      randomized crossover study in 20 patients (age, 56+/-9 years; body mass index,
      27.5+/-4 kg/m2) with severe hyperlipoproteinemia and coronary heart disease who
      are treated by statins and regular LDL apheresis. Both treatment periods (placebo
      and ezetimibe) were separated by a 5-week washout period. Low-density lipoprotein
      subtype distribution was determined at the end of each treatment period before
      apheresis by density gradient ultracentrifugation (LDL1, 1.020-1.024; LDL2, 1.025
      1.029; LDL3, 1.030-1.034; LDL4, 1.035-1.040; LDL5, 1.041-1.047; LDL6, 1.048
      1.057; LDL7, 1.058-1.066 g/mL). Overall, the LDL subtype distribution did not
      change significantly (large-buoyant LDL [LDL1+LDL2], 17.2%+/-6.4% vs 16.3%+/
      7.1%; intermediate LDL [LDL3+LDL4], 49.3%+/-4.5% vs 48.2%+/-5.2%; small-dense LDL
      [LDL5+LDL6+LDL7], 33.5%+/-8.0% vs 35.5%+/-10% during placebo and ezetimibe
      treatments, respectively). With respect to the individual LDL subfractions,
      cholesterol was significantly (P<.05, Wilcoxon test) reduced by ezetimibe in LDL1
      to LDL5 with a somewhat more pronounced reduction in larger LDL (mean+/-SD, 
      20%+/-28%, -17%+/-32%, -14%+/-25%, -13%+/-27%, -11%+/-21%, -7%+/-21%, -4%+/-19%;
      median, -28%, -12%, -18%, -16%, -4%, -4%, -2% for LDL subfractions 1-7,
      respectively). We therefore conclude that ezetimibe decreases cholesterol in
      nearly all LDL subfractions. Although this was established in patients
      concomitantly treated with statins and apheresis, this may also hold true in
      other clinically relevant situations.

PMID- 16631436
TI  - Hypocholesterolemic action of the selective estrogen receptor modulator
      acolbifene in intact and ovariectomized rats with diet-induced
      hypercholesterolemia.
AB  - Acolbifene (ACOL) is a fourth-generation selective estrogen receptor modulator
      (SERM) that has strong and pure antiestrogenic properties toward estrogen
      sensitive cancers, but improves energy and lipid metabolism in an estrogen-like
      fashion in rodent models. The aim of this study was to determine the potency of
      ACOL to reduce cholesterolemia in a dietary model of hypercholesterolemia and to
      establish its mechanisms of action. Intact and ovariectomized (OVX) female rats
      were treated for 3 weeks with ACOL, and serum cholesterol and liver determinants
      of cholesterol metabolism were assessed. Acolbifene prevented both diet- and
      ovariectomy-induced weight gain and completely prevented diet-induced
      hypercholesterolemia. Relative to a reference chow diet, the high-cholesterol
      diet decreased the high-density lipoprotein (HDL) cholesterol fraction, which
      remained unaffected by ACOL, indicating that in hypercholesterolemic conditions,
      ACOL modulated only the non-HDL fraction. No impact of ACOL on determinants of
      liver cholesterol synthesis was observed. In contrast, ACOL increased hepatic low
      density lipoprotein receptor protein in both intact and OVX rats, which was
      negatively correlated with serum total and non-HDL cholesterol (r=-0.59,
      P<.0001), suggesting a contribution of receptor-mediated hepatic uptake of
      cholesterol-rich lipoproteins to the hypocholesterolemic effect of ACOL. These
      findings establish that ACOL retains its powerful cholesterol-lowering action in
      diet-induced hypercholesterolemia and suggest that the SERM acts in such
      conditions through favoring hepatic low-density lipoprotein receptor-mediated
      uptake of cholesterol transported by non-HDL lipoprotein fractions.

PMID- 16631437
TI  - Insulin absorption: a major factor in apparent insulin resistance and the control
      of type 2 diabetes mellitus.
AB  - Our experience over many years from 2 diabetes clinics with large patient
      populations indicated that, apparently, excessive doses of intermediate-acting
      insulin preparations (150-300 U of NPH insulin), alone or in combination with
      rapid-acting insulin, generally did not result in acceptable control of fasting
      blood glucose. We hypothesized that insulin resistance at the tissue level and
      the known variability of insulin absorption were not satisfactory explanations.
      To deal with the ambiguities of available data on insulin absorption, we elected
      to measure insulin bioavailability via a different approach. Thirteen
      publications provided plasma insulin concentrations after the subcutaneous
      administration of defined doses of insulin. These data were then analyzed by
      noncompartmental analysis and by standard pharmacokinetic methods. Analyses
      required only knowledge of the areas under the plasma insulin curve and the
      metabolic clearance rate of insulin. Both of these are parameters measurable with
      considerable accuracy. Quantitative pharmacokinetic analysis of published insulin
      absorption curves for insulin administered subcutaneously revealed mean
      absorption levels for regular and lispro insulin of 70 to 80%, 30% or less for
      NPH insulin, and 30 to 40% for lente insulin. In conclusion, poor absorption of
      intermediate-acting insulin preparations, or combinations of intermediate- and
      rapid-acting insulin preparations, explains the difficulty in lowering blood
      glucose in patients with type 2 diabetes mellitus who have had long-standing
      disease, are insulin resistant, and have a flat insulin response to a glucose
      load.

PMID- 16631438
TI  - Clinical significance of homocysteine in elderly hospitalized patients.
AB  - Serum homocysteine levels, which increase with age, are now recognized as a
      vascular risk factor and are related to the development of heart failure and
      dementia in the elderly. However, relatively low serum homocysteine levels have
      also been reported to be an adverse prognostic factor in dialysis patients. The
      objective of the study was to analyze the prevalence, clinical significance, and
      prognostic value of serum homocysteine levels in patients older than 65 years,
      admitted to a general internal medicine hospitalization unit. We studied 337
      hospitalized patients, 184 males and 153 females, aged 77.2+/-0.4 years, whose
      admission was not determined by an acute vascular event. We recorded past
      vascular events and vascular risk factors. We determined the body mass index
      (weight in kilograms divided by the square of height in meters), and cholesterol,
      triglyceride, folate, vitamin B12, and homocysteine levels. We also studied 36
      control subjects (18 males and 18 females) of similar age. After discharge, we
      assessed the survival status of 301 patients by telephone recall. Survival curves
      were plotted by the method of Kaplan and Meier. Median survival was 1186 days.
      The 15th (9.6 micromol/L) and 50th (14.4 micromol/L) percentiles, as the lowest
      and highest cut-off points, were empirically defined as those related to a
      shorter survival. Serum homocysteine concentration was significantly positively
      correlated with age and serum creatinine and albumin concentrations, and
      negatively correlated with serum cobalamin and folate concentrations. The average
      serum homocysteine concentration for the patients group, as a whole, was 16.5+/
      0.5 micromol/L, not significantly different from the control group, but with a
      much greater dispersion, as patients with congestive heart failure or cognitive
      impairment had higher serum homocysteine concentrations, and patients with
      sepsis, leukocytosis, and hypoalbuminemia had lower concentrations. Malnutrition
      was associated both with abnormally high and low homocysteine concentrations, and
      abnormally low and abnormally high homocysteine concentrations were both
      associated with higher mortality. In conclusion, low homocysteine levels in
      elderly non-vitamin-supplemented hospitalized patients should not be interpreted
      as a protective factor in some individuals. Instead, it may be considered as an
      effect of an inflammatory-malnutrition process associated with a poor prognosis.

PMID- 16631439
TI  - Maternal folic acid supplementation to dams on marginal protein level alters
      brain fatty acid levels of their adult offspring.
AB  - Studies on fetal programming of adult diseases have highlighted the importance of
      maternal nutrition during pregnancy. Folic acid and long-chain essential
      polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth.
      However, folic acid effects may also involve alteration of LC-PUFA metabolism.
      Because marginal deficiency of LC-PUFAs during critical periods of brain growth
      and development is associated with risks for adult diseases, it is highly
      relevant to investigate how maternal supplementation of such nutrients can alter
      brain fatty acid levels. We examined the impact of folic acid supplementation,
      conventionally used in maternal intervention, on brain essential fatty acid
      levels and plasma corticosterone concentrations in adult offspring at 11 months
      of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets
      either with 18 g protein/100 g diet (control diet) or treatment diets that were
      marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg
      folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g
      protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard
      laboratory diet with 18 g protein/100 g diet. All male adult offspring in the
      FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control
      adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n
      6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were
      also lower (P<.05) when compared with the MP group. Plasma corticosterone
      concentrations were higher (P<.05) in male adult offspring from the FAS/MP group
      compared with control as well as the MP adult offspring. Results suggest that
      maternal folic acid supplementation at MP intake decreased brain docosahexaenoic
      acid levels probably involving corticosterone increase.

PMID- 16631440
TI  - Dietary fatty acids differentially modulate messenger RNA abundance of low
      density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase,
      and microsomal triglyceride transfer protein in Golden-Syrian hamsters.
AB  - Dietary fatty acids modulate plasma and intracellular cholesterol concentrations.
      Circulating non-high-density lipoprotein cholesterol (nHDL-C) concentration is
      determined by rates of hepatic very low-density lipoprotein assembly and
      secretion, and clearance of subsequent metabolic products. The effect of dietary
      fat (butter, traditional margarine, soybean oil, and canola oil) was assessed
      with respect to plasma lipids, hepatic lipid composition, and messenger RNA
      (mRNA) abundance of low-density lipoprotein (LDL) receptor, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, sterol regulatory element-binding
      protein (SREBP) 2, and microsomal triglyceride transfer protein (MTP) in the
      Golden-Syrian hamster (Charles River Laboratories, Wilmington, MA). Hamsters were
      fed with a nonpurified diet (6.25 fat g/100 g) with 0.1 g cholesterol/100 g
      (control diet) or control diet with an additional 10 g experimental fat/100 g for
      12 weeks. Hamsters fed with the control diet, unsaturated fats (canola and
      soybean oils), and margarine, relative to butter, had significantly lower total
      cholesterol and nHDL-C and triglyceride concentrations. Additional dietary fat,
      regardless of fatty acid profile, resulted in higher hepatic cholesterol
      concentrations. In contrast, relative to the control diet-, butter-, or margarine
      fed hamsters, these changes were associated with a 4- and 8-fold higher LDL
      receptor and 5- and 9-fold higher SREBP mRNA abundance, in hamsters fed with
      canola and soybean oils, respectively. MTP mRNA, a marker of very low-density
      lipoprotein particle formation, was higher in canola- and soybean oil-fed
      hamsters relative to the control diet-fed hamsters, although differences were
      modest. These results suggest that the substitution of canola and soybean oils
      for butter results in lower nHDL-C concentrations that may be related to
      increased mRNA abundance of the LDL receptor, SREBP-2, and MTP genes.

PMID- 16631441
TI  - Maternal protein intake in the pregnant rat programs the insulin axis and body
      composition in the offspring.
AB  - Evidence to support an association between early nutrition and the development of
      obesity in the rat is equivocal. In this study we have investigated the postnatal
      growth, glucose tolerance, and adipocyte function of the offspring from pregnant
      rats fed with diets containing either 20% or 8% protein during gestation. By 25
      weeks of age, the female offspring of dams fed with the diet containing 8%
      protein had a significantly lower adult body weight due in part to a decrease in
      body fat. The peak concentration of insulin after oral administration of a
      glucose dose was significantly lower in both the male and female offspring of the
      dams fed with the diet containing 8% protein. However, the ability of insulin to
      stimulate lipogenesis or suppress lipolysis in fat cells isolated from the
      offspring was not influenced by the prenatal diet. Hepatic phosphoenolpyruvate
      carboxykinase activity was reduced in female offspring of dams fed with the diet
      containing 8% protein. These results show that adult body composition is
      determined during the prenatal period as a result of programming of the insulin
      axis. This metabolic programming influences hepatic metabolism; however, there is
      no evidence for a programmed change in adipocyte function.

PMID- 16631442
TI  - Is visceral adipose tissue a determinant of von Willebrand factor in overweight
      and obese premenopausal women?
AB  - Visceral obesity has been associated with an increased cardiovascular risk.
      However, the exact mechanisms are not completely clear. In this study we
      investigated the relationship between von Willebrand factor (vWF) and visceral
      adipose tissue (VAT) in a group of 181 overweight and obese premenopausal women
      visiting the weight management clinic of a university hospital. von Willebrand
      factor antigen (vWF:Ag), plasminogen activator inhibitor 1 (PAI-1) activity, VAT
      (computed tomography scan), insulin resistance (homeostasis model assessment of
      insulin resistance), and other anthropometric and metabolic parameters were
      measured. Subjects with VAT in the highest quintile had significantly higher
      levels of vWF:Ag (171+/-60 vs 129+/-40%; P=.001) and PAI-1 (24.7+/-8.5 vs 15.2+/
      12.0 AU/mL; P<.001) compared with subjects in the lowest quintile. After
      correction for fat mass and homeostasis model assessment of insulin resistance
      the difference was still significant for vWF:Ag (P=.046), but not for PAI-1
      (P>.05). Stepwise multiple regression analysis showed VAT and insulin resistance
      as independent determinants of vWF:Ag, whereas waist circumference, high-density
      lipoprotein cholesterol, and insulin resistance were independent determinants of
      PAI-1 activity. In a subgroup of 115 patients, we measured high-sensitivity C
      reactive protein and found it to influence the relationship between VAT and
      vWF:Ag (r=0.16; P=.088), whereas the relationship with PAI-1 was still
      significant (r=0.21; P=.025). The results from this preliminary study suggest a
      plausible relation between visceral obesity and endothelial activation, possibly
      mediated by low-grade inflammation.

PMID- 16631443
TI  - Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction
      in patients with chronic renal failure undergoing hemodialysis.
AB  - In patients with chronic renal failure undergoing hemodialysis (HD), the presence
      of silent cerebral infarction (SCI) is associated with high mortality. Plasma
      total homocysteine (tHcy), which increases with renal dysfunction, has been
      flagged as a novel predictor for cerebrovascular events. We tested the hypothesis
      that the presence of SCI correlates with tHcy in HD patients. Based on brain
      magnetic resonance imaging findings, 44 patients undergoing HD were divided into
      a with-SCI group (61+/-9 years [mean+/-SD]; n=24) and a without-SCI group (60+/-8
      years, n=20), in whom 24-hour ambulatory blood pressure monitoring was performed.
      The number of patients with diabetes or hypertension was not different between
      the 2 groups. We made the following observations: (1) the percentage of smokers
      was higher in the with-SCI group than in the without-SCI group (P<.05); (2)
      plasma levels of high-density lipoprotein cholesterol were lower and tHcy was
      higher in the with-SCI group than in the without-SCI group (P<.05 and P<.0001,
      respectively); (3) and systolic ambulatory blood pressure and mean heart rate
      during nighttime were higher in the with-SCI group than in the without-SCI group
      (P<.05). Multivariate logistic analysis identified hyperhomocysteinemia as an
      independent and significant risk factor for SCI (odds ratio, 1.22; 95% CI, 1.10
      1.36; P<.01). Our findings indicate that plasma tHcy may be a novel useful
      predictor for SCI in patients with chronic renal failure undergoing HD.

PMID- 16631444
TI  - Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with
      coronary artery disease.
AB  - Triglycerides (TGs) are vehicled by multiple particles with different abilities
      to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies
      may or may not contain apolipoprotein E (apoE) molecules: in this study, we
      evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary
      atherosclerosis. We selected a group of males with premature coronary artery
      disease (CAD) without any of the classical nonlipid risk factors and/or high
      plasma lipid levels and evaluated the plasma concentration of TRL subspecies in
      comparison with healthy controls. Patients with CAD and controls had total
      cholesterol and TG levels within the normal range (despite slightly, even if
      significantly, higher TG levels in patients with CAD) and low-density lipoprotein
      cholesterol levels near optimal values. Nevertheless, patients with CAD had
      significantly lower high-density lipoprotein cholesterol, smaller low-density
      lipoprotein peak particle size, and a reduced HDL2b subfraction than controls. In
      addition, we observed higher concentrations of total TRL in patients with CAD
      together with a selective increase in apoE-rich particles. All these data were
      confirmed after correction for TG levels. We also investigated which parameters
      were associated with the spread of coronary atherosclerosis. Subjects with a
      single-vessel disease had selectively lower levels of apoE-rich fractions than
      patients with a multivessel disease. This was confirmed by multivariate analysis.
      Patients with a premature CAD free of nonlipid conventional risk factors, despite
      not having elevated lipid levels, show several lipoprotein abnormalities. Besides
      known atherogenic alterations, the accumulation of apoE-rich TRL subfractions may
      represent an additive factor that can potentially promote and initiate the
      atherosclerotic process.

PMID- 16631445
TI  - Persistent suppression of resting energy expenditure after acute hypoxia.
AB  - Resting energy expenditure (REE) is known to be influenced by various ambient
      conditions such as oxygen supply. Investigations in healthy subjects during acute
      hypoxia revealed a drop in REE, but persistent effects after hypoxia had ended
      have not been examined so far. Although indirect calorimetry is a well
      established method to measure REE, it may lead to false conclusions when
      hyperventilation, rise in lactate or catecholamines, and decrease of food intake
      accompany hypoxia. Therefore, we determined REE in healthy men after hypoxia had
      ended and under conditions of controlled energy supply during a glucose clamp. In
      a double-blind crossover study design, we induced hypoxia for 30 minutes by
      decreasing oxygen saturation to 75% (vs 96% in a control session) in 13 healthy
      men. Indirect calorimetry was performed at baseline and 150 minutes after hypoxia
      had ended. Plasma glucose was held stable between 4.5 and 5.5 mmol/L, and lactate
      as well as catecholamine concentrations were monitored. In parallel, we measured
      alterations in hormones of the hypothalamic-pituitary-thyroid axis, which is one
      known factor mediating changes in REE. Resting energy expenditure was decreased
      after hypoxia (from 1656+/-80 to 1564+/-97 kcal/d) as compared with the normoxic
      control condition (1700+/-82 to 1749+/-79 kcal/d, P=.037), whereas the
      respiratory quotient remained stable (P=.79). Plasma lactate, catecholamine
      levels, and the pituitary thyroid secretory activity were unchanged after hypoxia
      (P>.2). Our data demonstrate that the REE decrease persists 150 minutes after
      acute hypoxia, indicating an adaptation of energy metabolism. This should be
      valued as an additive pathogenic factor in diseases with disturbed energy
      metabolism.

PMID- 16631446
TI  - Evaluation of insulin sensitivity and glucose effectiveness during a standardized
      breakfast test: comparison with the minimal model analysis of an intravenous
      glucose tolerance test.
AB  - There is a need for reliable measurements of insulin sensitivity (SI) simpler
      than the euglycemic hyperinsulinemic clamp or the intravenous glucose tolerance
      test (IVGTT), which could be used when the simpler surrogates based on fasting
      insulin (Ib) and glucose (Gb) lose their validity. Several evaluations of SI
      derived from oral glucose tolerance test (OGTT) or its physiologic form, the
      standardized breakfast test (SBT), have been proposed. We aimed at determining
      which SBT-derived measurements of SI give the best prediction of the values
      obtained with the minimal model analysis of an IVGTT. Twenty-eight subjects (23
      females and 5 males; age, 44.3+/-0.6 years) with a wide range of glucose
      tolerance randomly underwent a hyperglucidic SBT and an IVGTT with minimal model
      analysis. Correlations of 35 indices (converted if appropriated into similar
      units) with IVGTT-derived SI were calculated, and the accuracy of the empiric
      formulas obtained with the 11 best predictions were evaluated with Bland-Altman
      plots. Subjects covered all the spectrum of SI between 0.19 and 21.3 min
      1/(microU.mL-1)x10(-4). Eight procedures yielded satisfactory predictions of
      minimal model SI: (1) SI (from Matsuda's composite index)=-1.24+65/(IbGbImGm)
      0.5; (2) SI=1.89+2690/(IbGbImGm); (3) SI (from Bennett's index)=-2.93+5.16/(log
      Ibxlog Gb); (4) SI (from Sluiter's index)=0.2+2400/(IpGp); (5) SI=
      8.54+38.4/(Belfiore's ISI index); (6) SI (from Cederholm's formula)=76/(Gm log
      Im); (7) SI=0.248+0.947/GbIm; (8) SI (from Mari's "oral glucose insulin
      sensitivity" index)=oral glucose insulin sensitivity/Ip; (9) Caumo's model.
      Glucose effectiveness Sg can also be accurately predicted by the following
      formula: Sg=2.921e-0.185(G60- Gb) (Ip=insulin peak; Gp=glucose peak; Ia=insulin
      area; Ga=glucose area; G60=glycemia at 60 minutes). The hyperglucidic SBT can
      provide accurate evaluations of SI and Sg, either by elaborated models or by
      simple empiric formulas.

PMID- 16631447
TI  - Insulin decreases intracellular oxidative stress in patients with type 2 diabetes
      mellitus.
AB  - Patients affected by diabetes mellitus have oxidative stress with an impaired
      glutathione (GSH) redox state. The objective of this study was to determine the
      influence of insulin on oxidative stress, defined as a reduced intracellular
      GSH/GSH disulfide (GSSG) ratio and lipid peroxidation by plasma thiobarbituric
      acid reactive substances (TBARSs) in patients with type 2 diabetes. Two
      experimental interventions were used: (1) measurement of GSH/GSSG ratio after
      insulin incubation in erythrocytes from 10 type 2 diabetic patients, and (2)
      measurement of intraerythrocytic GSH/GSSG ratio and plasma TBARS in 14 type 2
      diabetic patients during an in vivo hyperinsulinemic condition obtained from a
      euglycemic hyperinsulinemic clamp study. We confirmed that our patients underwent
      oxidative stress as shown by the significant difference in intracellular GSH/GSSG
      ratio in diabetic patients as compared to controls (13.56+/-3.84 vs 27.89+/-8.37,
      P<.0001). We found a significant elevation in the GSH/GSSG ratio after 2 hours of
      incubation with insulin in erythrocytes from diabetic patients (11.56+/-1.98 to
      15.61+/-2.62, P<.001). During the clamp studies, GSH/GSSG ratio had already
      increased after 60 minutes and even more after 120 minutes (baseline, 15.04+/
      4.19; at 60 minutes, 19.74+/-6.33; at 120 minutes, 25.33+/-11.15; P<.0001). On
      the contrary, no significant changes were observed in plasma TBARS (3.59+/-0.77
      to 3.56+/-0.83, NS). We conclude that insulin in patients with type 2 diabetes
      mellitus can reduce intracellular oxidative stress through increased GSH/GSSG
      ratio.

PMID- 16631448
TI  - Is leptin the causal factor of the changes in food intake observed after
      glucocorticoid infusion?

PMID- 16631452
TI  - The evolution of imaging in advanced prostate cancer.
AB  - Medical advances will be driven by the enhancement of imaging for diagnosis,
      refinement of treatment, and evaluation of treatment efficacy. The convergence of
      technology in materials science, biology, and the computer industry has greatly
      advanced diagnostic imaging. Precision in control of the spatial and temporal
      properties of light and its heterogeneous scattering properties have extended our
      capability for imaging. Refinements in radioimmunoscintigraphy for image
      acquisition, fusion of images, and outcome data now suggest use for image-guided
      therapy. Novel MRI agents appear to provide significant imaging capabilities to
      detect malignant lymph nodes. Future applications of optical coherence
      tomography, electron paramagnetic resonance imaging, nanotechnology, molecular
      imaging, and hyperspectral spectroscopy promise further refinements to image
      tissues for diagnosis.

PMID- 16631453
TI  - Biochemical recurrence after localized treatment.
AB  - The quoted incidence of biochemical recurrence (BCR) after localized treatment
      varies significantly and depends on numerous well-known prognostic factors;
      however, it likely occurs in at least 30%-40% of patients who receive localized
      treatment. Because the clinical significance of BCR is often unclear, and depends
      in many cases on unknown factors, it is difficult to select the best treatment
      and determine when best to institute that therapy. This review examines some of
      the issues associated with BCR and attempts to shed some light on this common but
      controversial clinical scenario. Some treatment strategies discussed in this
      article include salvage radiotherapy after radical prostatectomy, salvage therapy
      after radiotherapy, and hormonal therapy.

PMID- 16631454
TI  - Combined androgen blockade: an update.
AB  - The use of combined androgen blockade therapy in prostate cancer management
      remains controversial. This article reviews the effect of the different non
      steroid androgens in blocking androgen-independent activation of the androgen
      receptor in the androgen-depleted environment, and the potential benefit of
      bicalutamide in comparison to the first generation of anti-androgens (flutamide
      and nilutamide). An estimate of the benefit of combined therapy with bicalutamide
      suggests there is a high probability that bicalutamide 50 mg as combined therapy
      provides a survival advantage over castration alone. This treatment must be
      balanced against the potential for an increase in side-effects and a consequent
      adverse effect on the patient's quality of life.

PMID- 16631455
TI  - Intermittent androgen deprivation: clinical experience and practical
      applications.
AB  - Prostate cancer is more frequently being diagnosed at an earlier age, men are
      dying of prostate cancer at an older age, and men are now treated with androgen
      deprivation for biochemical relapse. As a result, the amount of time that
      patients are potentially subjected to androgen deprivation is increasing.
      Intermittent androgen deprivation (IAD) has been investigated as a potential
      alternative to continuous androgen deprivation (CAD) in order to improve quality
      of life and potentially delay the progression to androgen independence. Along
      with the increased use of primary hormonal therapy in clinically localized
      prostate cancer, IAD may supplant the traditional surgical or radiotherapy
      options, specifically in men who have underlying co-morbidities and decreased
      life expectancy. There are ongoing multi-institutional, randomized trials that
      will lend insight into the utility, efficacy, and feasibility of IAD versus CAD.
      This article discusses the theoretical benefits and rationale of IAD and reviews
      the completed and on-going IAD trials. Finally, the controversies, practical
      applications, and future directions of IAD are addressed.

PMID- 16631456
TI  - Managing complications of androgen deprivation therapy for prostate cancer.
AB  - With the increase in the number of prostate cancer cases seen in the United
      States, the use of androgen deprivation therapy (ADT) as a form of treatment has
      continued to rise. With the increasing use of ADT, it is important for the
      urologist to recognize the potential side effects from the use of ADT and ways in
      which to minimize or eliminate the risks from these side effects. This article
      describes the potential complications of ADT and the recommendations for
      treatment or prevention of these complications. In addition,we examine the role
      of nontraditional forms of ADT and the potential benefits they offer.

PMID- 16631457
TI  - The role of bisphosphonates in preventing skeletal complications of hormonal
      therapy.
AB  - Androgen deprivation therapy (ADT) is associated with a significant decrease in
      bone mineral density (BMD), and continued exposure seems to increase the risk of
      osteoporotic fracture in men who have prostate cancer treated with this strategy.
      Men who have prostate cancer may have low BMD before initiation of ADT.
      Bisphosphonates are pyrophosphate analogs that decrease bone resorption primarily
      through direct inhibition of osteoclast activity and proliferation. Several
      bisphosphonates have been evaluated in randomized clinical trials, and the
      cumulative data show that these medications increase or maintain BMD in men
      receiving ADT for prostate cancer. The effect on clinical fractures has not been
      assessed adequately, but bisphosphonates offer an important potential treatment
      modality to reduce the risk of osteoporotic fracture in this population of men.

PMID- 16631458
TI  - Mechanisms leading to the development of hormone-resistant prostate cancer.
AB  - Advanced and metastatic prostate cancers remain potentially lethal tumors.
      Although androgen deprivation therapy remains the most effective treatment,
      patients who progress to androgen independence die of their disease. This article
      focuses on the mechanisms by which hormone resistance develops, including the
      reactivation of androgen receptor during androgen deprivation therapy, the role
      of cancer stem cells, and the emergence of epithelial-mesenchymal transition
      cells, which have increased metastatic potential. It is through an enhanced
      understanding of these mechanisms that new therapies can be developed to combat
      this disease.

PMID- 16631459
TI  - Advancing prostate cancer: treatment options for the urologist.
AB  - Today's urologists often face the dilemma of how to treat patients who have
      advancing prostate cancer. The diversity of this patient population makes
      treatment decisions challenging. For over 60 years the mainstay of treatment for
      patients who have advancing prostate cancer has been androgen deprivation
      therapy. Now there are new chemotherapeutic options, novel hormone manipulations,
      and other adjunctive therapies available. Based on a case presentation, the
      authors have attempted to outline for the practicing urologist, a logical
      progression of treatment options for advancing prostate cancer.

PMID- 16631460
TI  - Radiation therapy and radio-nuclides for palliation of bone pain.
AB  - Bone pain from metastatic prostate cancer can be effectively palliated by a
      single fraction of 8 Gy with no increase in toxicity, which can occur with more
      protracted fractionation schemes. Re-treatment, if required, is simple and
      effective. For multiple painful sites on the same side of the diaphragm, hemi
      body radiotherapy is rapidly effective; pre-medication with odanstetron and
      steroids has markedly improved tolerance. For multiple painful sites on both
      sides of the diaphragm, radiopharmaceuticals can be considered but will not treat
      adjacent soft tissue disease or neurologic compromise.

PMID- 16631461
TI  - Changing perspectives of the role of chemotherapy in advanced prostate cancer.
AB  - The use of cytotoxic chemotherapy in advanced prostate adenocarcinoma has been
      validated by the recent demonstration of survival benefit in two large randomized
      phase III trials. Before publication of these landmark trials, SWOG 9916 and TAX
      327, no chemotherapeutic regimen had shown survival benefit in the treatment of
      androgen independent prostate cancer (AIPC). These trials provide new
      encouragement for the use of chemotherapy in all stages of disease. Improved
      communication between medical and urologic oncologists and early patient referral
      for clinical trial participation remains essential for identifying new
      chemotherapeutic regimens with improved activity in AIPC and for defining the
      role of chemotherapy in earlier-stage disease. This article discusses the role of
      chemotherapy as the current standard of care for the treatment of AIPC and
      provides a historical perspective of the trials that preceded the development of
      current docetaxel-based regimens.

PMID- 16631462
TI  - Complementary and alternative medicine for advanced prostate cancer.
AB  - Complimentary and alternative medicines (CAM) have increased drastically in
      popularity in the past decade. These are largely in the form of nutritional
      supplements. Despite a wealth of information sources on the subject, the
      fundamental problem with CAM therapies is a dearth of evidence-based medicine.
      Advanced prostate cancer has significant long-term morbidity, and there is a
      growing interest in alternative and complimentary forms of therapy that will
      improve the outcomes of patients who have recurrent or advanced prostate cancer
      while obviating the need for more toxic forms of therapy. In this article we
      summarize the use of some of the more common CAM nutritional supplements and
      review the scientific data that are available to support their use.

PMID- 16631463
TI  - Future innovations in treating advanced prostate cancer.
AB  - Many novel techniques for the treatment of prostate cancer are being aggressively
      investigated because prostate cancer is prevalent in the population and the
      current treatments for advanced prostate cancer are woefully inadequate. Although
      the current treatment options prolong life, most patients will eventually
      experience local recurrence or develop advanced disease. A greater understanding
      of the molecular events underlying cancer has enabled investigators to explore
      gene therapy approaches that are targeted against these molecular events. This
      article discusses antiangiogenic therapy, immune based therapy, and gene therapy.
      Any of these experimental modalities could be developed to replace hormone
      ablation therapy which causes unpleasant side effects, decreases the quality of
      life of the patient, and only temporarily controls the disease.

PMID- 16631464
TI  - Methylthioadenosine phosphorylase gene deletions are frequently detected by
      fluorescence in situ hybridization in conventional chondrosarcomas.
AB  - Chondrosarcomas are the second most common primary malignant tumor of bone.
      Chemotherapy for conventional chondrosarcomas is generally ineffective.
      Methylthioadenosine phosphorylase (MTAP) is a ubiquitous enzyme, essential in the
      salvage pathway of adenine and in methionine synthesis. MTAP-deficient cells are
      more susceptible than wild-type cells to pharmacologic inhibitors of de novo
      purine synthesis. Homozygous deletions of MTAP have been reported in hematologic
      and solid tumor malignancies. Based on these observations, we investigated the
      frequency of MTAP deletions in conventional, grade II chondrosarcomas by
      fluorescence in situ hybridization (FISH) analysis: 23 conventional, grade II
      chondrosarcoma patient samples from the Cleveland Clinic Foundation were analyzed
      for MTAP deletions. Nuclei were successfully extracted from 14 of 23 samples (61%
      evaluable) for FISH analysis: 7 of 14 samples (50%) showed either homozygous or
      hemizygous deletion of the MTAP gene, 6 of 14 (43%) failed to show deletion, and
      1 of 14 (7%) was inconclusive. These findings suggest that approximately one-half
      of conventional, grade II chondrosarcomas may be preferentially sensitive to
      pharmacologic inhibitors of de novo purine synthesis. The present study led to
      development by the Intergroup Coalition Against Sarcomas of a phase II trial of
      pemetrexed, a multitargeted anti-folate, for advanced chondrosarcomas.

PMID- 16631465
TI  - ATM alterations in childhood non-Hodgkin lymphoma.
AB  - ATM gene alterations and impaired ATM protein expression have been described in
      various adult lymphoproliferative malignancies, suggesting that ATM contributes
      to lymphomagenesis. The present study investigated the prevalence of ATM gene and
      ATM protein expression alterations in sporadic childhood non-Hodgkin lymphoma
      (NHL). Twenty-seven cases of NHL were screened for ATM mutations by denaturing
      high-performance liquid chromatography (DHPLC). Direct and indirect criteria,
      including in silico tools, were used to classify the gene alterations. The
      methylation status of the ATM promoter CpG island was determined in 25 samples;
      ATM protein expression was assessed by Western blot in 9 lymphomas. ATM
      alterations were detected in 12 NHLs (44%). Ten different heterozygous base
      substitutions were identified in 10 NHLs (37%). Five samples (19%) were found to
      harbor a gene alteration considered to be a mutation or a rare variant
      potentially pathogenic. In one case, an ATM mutation was found in the germline.
      Four NHLs (44%) showed reduced or absent ATM protein expression. Except for one
      sample, no definite genetic or epigenetic alteration was identified to account
      for impaired ATM protein expression. These observations document a high
      prevalence of ATM gene and protein expression alterations, suggesting that ATM is
      involved in childhood NHL.

PMID- 16631466
TI  - GATA1 mutations in acute leukemia in children with Down syndrome.
AB  - It has been reported that somatic mutations in the X-linked GATA1 gene are
      present in hematological clonal disorders in children with Down syndrome (DS). We
      analyzed retrospective samples of DS children with acute myeloid leukemia,
      transient leukemia (TL), and myelodysplastic syndrome (MDS) to test whether the
      specificity of GATA1 mutations can be helpful in distinguishing these
      hematopoietic disorders. A total of 49 samples were subjected to GATA1 mutation
      screening by direct sequencing and denaturing polyacrylamide gel electrophoresis
      (PAGE). Mutations in exon 2 of GATA1 were detected in six of eight DS-AML M7
      samples and in four of six DS-TL; no mutation was detected in 13 children with
      acute lymphoblastic leukemia (DS-ALL), 6 with DS-AML (M0, M2, and M5), 6 with DS
      MDS and in 8 DS infants without hematological disorders and 2 children with AML
      M7 without DS. Blast cells proportion in the sample represented a critical aspect
      on the sensitivity of mutation detection in GATA1, and a combination of sequence
      analysis and PAGE is necessary to detect mutations when blast percentage is low.
      The absence of detected mutations in any of the DS-MDS cases raises the question
      whether MDS in DS children is an intermediate stage between TL and AML M7, as
      previously suggested.

PMID- 16631467
TI  - Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in
      the risk of cervical cancer in India.
AB  - Human papilloma virus (HPV) infection is a major cause of cervix cancer, but a
      number of infected women do not develop invasive lesions, suggesting that HPV
      infection in itself is not a sufficient factor and that other cofactors, such as
      smoking, play an important role in development of cervix cancer. Alongside active
      cigarette smoking, passive smoking is an independent risk factor for cervix
      cancer. Smoking maintains cervical HPV infection longer and decreases potential
      of clearing an oncogenic infection. Thus, it is quite possible that polymorphism
      at detoxifying enzyme coding loci such as GSTM1, GSTT1, and GSTP1 may determine
      susceptibility to cervix cancer. This study evaluates the combined effects of
      genetic polymorphisms of GSTM1, GSTT1, and GSTP1 on susceptibility to cervical
      cancer and interaction of these genes with smoking. On individual analysis of
      GSTM1, GSTT1, and GSTP1, it was observed that passive smokers having genotypes
      GSTM1 (null) (OR = 7.0, 95% CI = 2.19-22.36, P = 0.0005), GSTT1 (null) (OR =
      10.2, 95% CI = 1.23-84.18, P = 0.02), and GSTP1 (ile/val) (OR = 6.4, 95% CI =
      2.25-18.38, P = 0.0005) have an increased risk of developing cervix cancer. It is
      thus concluded that cervical cancer risk is increased in passive smokers with
      GSTM1 (null), GSTT1 (null), and GSTP1 (ile/val) genotypes.

PMID- 16631468
TI  - Activating PTPN11 mutations play a minor role in pediatric and adult solid
      tumors.
AB  - The PTPN11 gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine
      phosphatase functioning as a signaling transducer. Germ-line PTPN11 mutations
      cause Noonan syndrome (NS), a developmental disorder characterized by an
      increased risk of malignancies. Recently, a novel class of activating mutations
      in PTPN11 has been documented as a somatic event in a heterogeneous group of
      leukemias. Because of the relatively higher prevalence of certain solid tumors in
      children with NS and the positive modulatory function of SHP-2 in RAS signaling,
      a wider role for activating PTPN11 mutations in cancer has been hypothesized.
      Here, we screened a number of solid tumors, including those documented in NS or
      in which deregulated RAS signaling occurs at significant frequency, for PTPN11
      mutations. No disease-associated mutation was identified in rhabdomyosarcoma (n =
      13), neuroblastoma (n = 32), melanoma (n = 50), thyroid (n = 85), and colon (n =
      48) tumors; a novel missense change, promoting an increased basal phosphatase
      activity of SHP-2, was observed in one glioma specimen. Our data document that
      deregulated SHP-2 function does not represent a major molecular event in
      pediatric and adult tumors, further supporting our previous evidence indicating
      that the oncogenic role of PTPN11 mutations is cell-context specific.

PMID- 16631469
TI  - Differentially expressed genes in the prostate cancer cell line LNCaP after
      exposure to androgen and anti-androgen.
AB  - Androgens play an important role in growth and maintenance of prostate cells. The
      actions of androgens are mediated by the androgen receptor (AR), a transcription
      factor member of the super-family of nuclear hormone receptors. Androgen
      regulated genes (ARGs) are potential markers for early diagnosis and treatment of
      prostate cancer patients. In the present study, we used DDRT-PCR (differential
      display reverse transcriptase polymerase chain reaction) technique in order to
      investigate differentially expressed genes in the prostate cancer cell line LNCaP
      after treatment with dihydrotestosterone and bicalutamide for 6, 24, and 48
      hours. Fifty-five differentially expressed fragments were isolated, cloned, and
      sequenced. Sequencing analysis of these fragments revealed 56 different
      transcripts that showed homology to transcription factors, cell cycle regulators,
      metabolic enzymes, and hypothetical proteins. Among the differentially expressed
      genes, SPA17 and DDEF2 were further validated using quantitative real time RT-PCR
      (qPCR) in a series of 25 prostate tumor samples. The DDEF2 gene is involved in
      adhesion and cell migration of monocytes, and the SPA17 gene might be involved in
      cellular signal transduction. The transcripts of both, SPA17 and DDEF2 genes,
      showed altered pattern of expression in the group of prostate tumors analyzed by
      qPCR. The differentially expressed genes identified in this study might provide
      new insights into the androgen signaling pathways in prostate cells.

PMID- 16631470
TI  - Deletion of MYC and presence of double minutes with MYC amplification in a
      morphologic acute promyelocytic leukemia-like case lacking RARA rearrangement:
      could early exclusion of double-minute chromosomes be a prognostic factor?
AB  - Gene amplification on double minutes is rarely found in acute myeloid leukemia
      (AML) and is often linked to poor prognosis. It is often associated with acute
      myeloid leukemia with differentiation (AML-M2) and is rarely reported in acute
      promyelocytic leukemia (APL), which is characterized in the vast majority of
      cases by the reciprocal t(15;17)(q22;q21) with resultant translation of an
      abnormal PML-RARA fusion protein. Most of the rare cases of APL that lack this
      translocation have a demonstrable RARA breakpoint. We report on a morphologic APL
      like case lacking t(15;17) and the RARA breakpoint and also has the deletion MYC
      of 8q24 associated with the occurrence of MYC amplification on double-minute
      chromosomes (dmin). Excessive exclusion of dmin was observed at the initial
      diagnosis. These findings are compared to the few cases previously reported in
      the literature.

PMID- 16631471
TI  - Low prevalence of Gs alpha mutations in somatotroph adenomas of children and
      adolescents.
AB  - Mutations in the gene coding for the alpha-subunit of the heterotrimeric
      stimulatory G protein Gs are the most frequently identified molecular events in
      the development of somatotroph adenomas in adults. In children and adolescents,
      somatotroph adenomas are rare, and only two cases with the Gs alpha mutation have
      been reported so far. In this study, we therefore investigated the prevalence of
      activating Gs alpha mutations in 17 patients younger than 20 years with pituitary
      growth hormone-secreting adenomas and examined the characteristics of mutation
      positive cases. The most common C-->T substitution in codon 201 was detected in
      two children. Interestingly, in contrast to the remaining cases, the adenomas
      positive for the Gs alpha mutation proved to be nonsporadic, but part of a
      syndrome associated with endocrine tumors in both individuals. Additional tests
      confirmed McCune-Albright syndrome in the first patient and multiple endocrine
      neoplasia type 1 syndrome in the second patient. In contrast to the findings in
      adult cases, somatotroph adenomas in young patients seem to carry somatic Gs
      alpha mutations at a lower frequency, and germ-line or early postzygotic
      mutational events may be responsible for the shortened latency of tumorigenesis.

PMID- 16631472
TI  - Metaphase cells with normal G-bands have cryptic interstitial deletions in 13q14
      detectable by fluorescence in situ hybridization in B-cell chronic lymphocytic
      leukemia.
AB  - Interphase fluorescence in situ hybridization (FISH) studies with D13S319 show
      that deletions of 13q14 are common in B-cell chronic lymphocytic leukemia (B
      CLL). In contrast, conventional cytogenetic studies in B-CLL seldom reveal
      abnormalities of chromosome 13. We hypothesized that chromosome 13 anomalies
      might not be detected because they are caused by cryptic deletions rather than by
      the absence of dividing B-CLL cells. To investigate this possibility, we used
      FISH with D13S319 to study metaphases from 12 patients known to have 13q- by
      interphase FISH. These same patients had normal chromosomes by conventional
      cytogenetic studies. As a result of this study, we report evidence that B-CLL
      metaphases with 13q- are not detected because these deletions are often cryptic
      and not visible by standard G-banding.

PMID- 16631473
TI  - Genomic array and expression analysis of frequent high-level amplifications in
      adenocarcinomas of the gastro-esophageal junction.
AB  - Adenocarcinomas of the gastroesophageal junction (GEJ) show frequent high-level
      amplifications (HLA), but the underlying genes are not well defined. We have
      characterized genomic gain in 14 GEJ carcinomas by array-based comparative
      genomic hybridization (aCGH). The most frequent gains and amplifications were
      detected at 7q (57%), 8q (57%), 17q (64%), and 20q (79%), with minimally
      amplified regions at 7q21.1, 8q24.2, 17q12, and 20q13.2. Five HLA were detected
      on 7q, one on 8q, two on 17q, and three on 20q. HLA of 8q24 and 17q12 were
      related to MYC and ERBB2, respectively. The HLA on 7q21 was associated
      recurrently with ABCB1, whereas the amplified region on 20q13 implicated ZNF217,
      BCAS1, and CYP24. RNA expression analysis of 11 adenocarcinomas by reverse
      transcription polymerase chain reaction was performed for cancer-related genes
      residing at 7q21 (ABCB1, ABCB4, CDK6, HGF, DMTF1, SRI, TP53AP1) and 20q13
      (ZNF217, BCAS1, CYP24, TNFRSF6B). The most frequently upregulated gene on 7q21
      was HGF (45%), but there was no association with genomic amplification. The most
      frequently overexpressed gene at 20q13 was BCAS1 (27%), which was related to HLA
      of this region (P = 0.006) in all three cases. We conclude that HLA occur often
      in GEJ adenocarcinomas. The gene responsible for the HLA of 7q21 requires further
      investigation, whereas BCAS1 is a good candidate for the frequent amplification
      of 20q13.

PMID- 16631474
TI  - Lack of TP53 and FMS gene mutations in children with myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are rare disorders in children. Molecular
      mechanisms underlying MDS in children are not yet completely understood.
      Considering the role of FMS and TP53 gene mutations in adult MDS patients, we
      analyzed mutations of these genes in a cohort of 35 children with MDS. Single
      strand conformation polymorphism polymerase chain reaction analysis performed on
      FMS codon 969 and TP53 exons 5-9 showed no mutations in the analyzed sequences.
      Our results suggest that molecular mechanisms of MDS evolution in children are
      different from those in adults.

PMID- 16631475
TI  - Loss of heterozygosity analysis of a candidate gastric carcinoma tumor suppressor
      locus at 7q31.
AB  - Gastric carcinoma is one of the most common malignancies in Asia. Although the
      allelic deletion of 7q has been reportedly associated with primary gastric
      carcinoma tumorigenesis, no predisposing genes in this region have been
      identified so far. Here, we report the results of genotype and loss of
      heterozygosity (LOH) analysis on 7q in this tumor. A panel of nine microsatellite
      markers distributed over the whole chromosome 7q was used for genotyping primary
      gastric carcinomas. Of 72 primary tumors LOH of D7S486 occurred in 24.0% (12/50)
      of cases. Fine mapping with 12 additional markers flanking D7S486 resulted in LOH
      of 30.36% (17/56) and defined one minimal deleted region in primary gastric
      carcinomas, a 90-kilobase region bounded by D7S2543 and D7S486 at 7q31.2. The
      allelic deletion correlates statistically with clinicopathologic variables. Our
      data suggest a possible link between putative tumor suppressor genes and gastric
      carcinoma in the 7q31 region.

PMID- 16631476
TI  - Molecular cytogenetic characterization of four previously established and two
      newly established Ewing sarcoma cell lines.
AB  - Most Ewing family tumors are identified by the characteristic translocation
      t(11;22)(q24;q12), resulting in a fusion protein EWS/FLI1 that acts as an
      aberrant transcription factor. In a minority of cases, the EWS gene is fused to
      another member of the ETS gene (ERG, ETV1, E1AF, and FEV). Though the oncogenic
      transforming capability of the EWS/FLI1 protein is highly suggestive, the exact
      pathway behind remains to be elucidated. The availability of cell lines may help
      in the understanding of underlying cellular processes. In this study, we have
      established two new Ewing sarcoma cell lines and characterized them with
      molecular cytogenetic tools. This technology was also applied on four other
      previously published Ewing sarcoma cell lines. Our findings in relation to
      previous data on similar tumors are discussed.

PMID- 16631477
TI  - A Ph-negative chronic myeloid leukemia with a complex BCR/ABL rearrangement and a
      t(6;9)(p21;q34.1).
AB  - Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent
      hematopoetic stem cell characterized by the presence of the Philadelphia (Ph)
      chromosome in more than 90% of patients. Cryptic or "masked" BCR/ABL gene
      rearrangements may be found in cases with a normal karyotype and in cases with
      the complex karyotype, in which typical t(9;22) is not visible at the microscopic
      level. Those rearrangements can now be detected by fluorescence in situ
      hybridization. Here, we report on a novel and complex Ph chromosome-negative CML
      case with a t(6;9)(p21;q34.1) in which the BCR/ABL fusion gene is located at
      6p21.

PMID- 16631478
TI  - Cytogenetic and fluorescence in situ hybridization analysis of a basal cell
      adenocarcinoma of the mandible.
AB  - Basal cell adenocarcinoma (BCAC) of the salivary glands is rare. Distant
      metastasis to the mandible from a salivary gland tumor is also considered rare.
      The cytogenetic finding of a case of metastatic BCAC of the mandible is
      described. We are unaware of earlier reports regarding cytogenetic findings of
      BCAC either at the primary site or at a distant metastasis site. An 80-year-old
      female with primary BCAC of the parotid salivary gland underwent parotidectomy
      and chemotherapy. One year later, a metastatic lesion in the mandible was found.
      Tissue specimens from the mandibular lesion were tested by the following
      pathologic methods: hematoxylin-eosin and immunohistochemistry for CK8/18,
      CK/903, vimentin, and smooth muscle actin. The characteristic histologic
      architecture of BCAC found in the mandible was similar to that of the earlier
      findings of the tumor in the parotid gland. A fresh sample from the mandibular
      lesion was examined by cytogenetics and fluorescence in situ hybridization
      (FISH), using centromeric probes for chromosomes 4, 8, 10, 18, and 22. A paraffin
      embedded sample of the primary tumor was also examined by FISH. Cytogenetic and
      FISH analyses of the mandibular metastatic lesion revealed a clone with a
      pericentric inversion of chromosome 17 and a clone with trisomy 4, respectively.
      Trisomy 4 was also found in the paraffin-embedded samples of the primary parotid
      tumor.

PMID- 16631479
TI  - Isochromosome 17q in MDS: a marker of a distinct entity.

PMID- 16631481
TI  - Postsurgical stability of oropharyngeal airway changes following counter
      clockwise maxillo-mandibular advancement surgery.
AB  - PURPOSE: This study evaluated oropharyngeal airway changes and stability
      following surgical counter-clockwise rotation and advancement of the maxillo
      mandibular complex. METHODS AND PATIENTS: Fifty-six adults (48 females, 8 males),
      between 15 and 51 years of age, were treated with Le Fort I osteotomies and
      bilateral mandibular ramus sagittal split osteotomies to advance the maxillo
      mandibular complex with a counter-clockwise rotation. The average postsurgical
      follow-up was 34 months. Each patient's lateral cephalograms were traced,
      digitized twice, and averaged to estimate surgical changes (T2-T1) and
      postsurgical changes (T3-T2). RESULTS: During surgery, the occlusal plane angle
      decreased significantly (8.6 +/- 5.8 degrees ) and the maxillo-mandibular complex
      advanced and rotated counter-clockwise. The maxilla moved forward (2.4 +/- 2.7
      mm) at ANS and the mandible was advanced 13.1 +/- 5.1 mm at menton, 10 +/- 4.4 mm
      at point B, and 6.9 +/- 3.7 mm at lower incisor edge. Postsurgical hard tissue
      changes were not statistically significant. While the upper oropharyngeal airway
      decreased significantly (4.2 +/- 3.4 mm) immediately after surgery, the narrowest
      retropalatal, lowest retropalatal airway, and the narrowest retroglossal airway
      measurements increased 2.9 +/- 2.7, 3.7 +/- 3.2, and 4.4 +/- 4.4 mm,
      respectively. Over the average 34 months postsurgical period, upper retropalatal
      airway increased 3.9 +/- 3.7 mm, while narrowest retropalatal, lowest
      retropalatal airway, and narrowest retroglossal airway remained stable. Head
      posture showed flexure immediately after surgery (4.8 +/- 5.9 degrees ) and
      extension postsurgically (1.6 +/- 5.6 degrees ). CONCLUSION: Maxillo-mandibular
      advancement with counter-clockwise rotation produces immediate increases in
      middle and lower oropharyngeal airway dimensions, which were constrained by
      changes in head posture but remain stable over the postsurgical period. The upper
      oropharyngeal airway space increased only on the longest follow-up.

PMID- 16631482
TI  - Three-wall orbital decompression superiority to 2-wall orbital decompression in
      thyroid-associated ophthalmopathy.
AB  - PURPOSE: We evaluated the results of the 2-wall and 3-wall orbital decompression
      in patients with Graves' disease. PATIENTS AND METHODS: In this study, we present
      a consecutive series of 12 patients (18 orbits) who were submitted to orbital
      decompression by endoscopic transnasal medial wall combined with transantral
      inferior wall approach and 7 patients (8 orbits) who were submitted to orbital
      decompression by endoscopic transnasal medial wall, transantral inferior wall
      combined with transcutaneous lateral wall approach. The degree of exophthalmos
      was evaluated with the Hertel exophthalmometer preoperatively and postoperatively
      in the 24th hour, and first, third, and ninth months. RESULTS: At the end of the
      third month, the exophthalmos decreased by a mean of 4.38 mm (range, 3 to 7 mm)
      with the 2-wall decompression and 7.75 mm (range, 5 to 12 mm) with the 3-wall
      decompression. Visual acuity maintained or improved during the follow-up period.
      Ocular motility disturbance occurred in 1 patient after 2-wall decompression and
      in 1 patient after 3-wall orbital decompression. Postoperatively, new-onset
      diplopia was seen in only 1 patient after 2-wall orbital decompression.
      CONCLUSION: The 3-wall (endoscopic transnasal medial wall, transantral inferior
      wall combined with transcutaneous lateral wall) approach is as safe as the 2-wall
      approach. Proptosis reduction is much better with the 3-wall orbital
      decompression.

PMID- 16631483
TI  - Effect of Gusuibu graft on bone formation.
AB  - PURPOSE: We compared the amount of new bone produced by Gusuibu in collagen
      grafts to that produced by bone grafts and collagen grafts. MATERIALS AND
      METHODS: Twenty bone defects were created in the parietal bone of 14 New Zealand
      White rabbits. In the experimental group, 5 defects were grafted with Gusuibu
      extract mixed with absorbable collagen sponge, and 5 defects were grafted with
      autogenous endochondral bone. In the control groups, 5 defects were grafted with
      absorbable collagen sponge alone (active control) and 5 were left empty (passive
      control). Animals were killed on day 14 and the defects were dissected and
      prepared for histologic assessment. Serial sections were cut across each defect.
      Quantitative analysis of new bone formation was made on 150 sections using image
      analysis. RESULTS: A total of 24% and 90% more new bone were present in defects
      grafted with Gusuibu in collagen grafts than those grafted with bone and
      collagen, respectively. No bone was formed in the passive control group.
      CONCLUSIONS: Gusuibu in collagen grafts have the effect of increased new bone
      formation locally and can be used as a bone graft material.

PMID- 16631484
TI  - Neurosensory alteration in the lower lip and chin area after orthognathic
      surgery: bilateral sagittal split osteotomy versus inverted L ramus osteotomy.
AB  - PURPOSE: This study investigated neurosensory disturbances in patients after
      orthognathic surgery in relation to differences in mandibular splitting methods
      and degree of surgical skill. PATIENTS AND METHODS: Forty-five patients who had
      undergone bilateral sagittal split ramus osteotomies (SSRO), and 21 (group L) who
      had undergone intraoral inverted L ramus osteotomies (ILRO), were examined for
      postsurgical neurosensory disturbances. Twenty-two (group S1) of the SSRO
      patients were treated by 11 surgeons who had little experience, and the others
      (23 patients; group S2) were treated by 2 skilled surgeons who had considerable
      experience. One of the 2 skilled surgeons was the only surgeon carrying out the
      ILRO procedure. The neurosensory tests employed included light touching using a
      Semmes-Weinstein monofilament tester (SW tester), electrical stimulation, and a
      questionnaire to determine changes in subjective sensations, at the time of each
      sensory evaluation. Neurosensory examinations were carried out bilaterally (132
      sides) at 1, 3, 6, and 12 months after surgery. RESULTS: More patients showed
      abnormal thresholds for the 2 measurement techniques in the SSRO group than in
      the ILRO group, and furthermore there were more such patients in group S1 than in
      group S2, at each measurement point. At 6 months after surgery, the number of
      patients with reduced sensitivity was significantly higher in group S1 than in
      group L (P < .05). In the SSRO group at each measurement point, the thresholds
      for the lower lip and chin were unrelated to the set-back (or advance) distance.
      By contrast, in group L only at the 1-month evaluation point, the thresholds for
      the lower lip and chin were significantly raised in patients whose setback
      distances were larger than average (P < .05). CONCLUSIONS: Postsurgical
      neurosensory disturbances of the lower lip and chin occur more frequently in SSRO
      patients treated by surgeons having little experience than in those treated by
      skilled surgeons, although the difference is not significant. Long-term prognosis
      for resolution of postsurgical neurosensory disturbances is better in ILRO
      patients than in SSRO patients. Although the width of movement of the split bone
      fragments has an influence on postsurgical neurosensory disturbances immediately
      after ILRO, the relationship becomes less obvious with time.

PMID- 16631485
TI  - Clinical impact of oral health indexes in dental extraction of hemophilic
      patients.
AB  - PURPOSE: Periodontal disease in patients with hemorrhagic disorders may lead to
      severe bleeding during dental treatment. This study evaluated the clinical impact
      of oral health indexes in hemophilic patients undergoing tooth extraction.
      PATIENTS AND METHODS: Thirty-one hemophilic patients underwent teeth extractions
      using autologous fibrin glue and an oral antifibrinolytic drug (epsilon
      aminocaproic acid). Oral health indexes (plaque, PI; gingival, GI; and decay
      missing-filling-teeth, DMFT index) were evaluated before tooth extraction.
      RESULTS: Postsurgical bleeding episodes were observed in 6 hemophilic patients (1
      severe, 3 moderate, and 2 mild type). The PI and GI index in the bleeding group
      were 1.8 and 1.7, respectively, and 1.8 for both of the non-bleeding groups (PI,
      P = .8; GI, P = .56). The global DMFT index was 18 in the bleeding group and 19.6
      in the non-bleeding group (P = .67). CONCLUSION: The status of oral health did
      not interfere with bleeding caused by dental extraction of hemophilic patients.

PMID- 16631486
TI  - Facial transplantation: a comprehensive review of the literature.
AB  - PURPOSE: Composite tissue allotransplantation has become a clinical reality and a
      major breakthrough in reconstructive surgery. The current boundary of dispute on
      composite tissue allotransplantation is regarding the full-face transplantation.
      The aim of this article is to provide a comprehensive overview of how facial
      allotransplantation has been approached in the scientific literature. MATERIAL
      AND METHODS: The selection of articles was conducted using PubMed at between
      January 2000 and September 2005. The search terms were "facial graft," "facial
      transplantation," and "facial allotransplant." The criteria of analysis were the
      category of articles and the presence of 6 items: 1) issues regarding the donor;
      2) psychological impact on the recipient; 3) surgical risks; 4) immunologic
      risks; 5) socio-cultural aspects; and 6) expense. RESULTS: Thirty-eight articles
      were included. The first article was published in 2002. Most articles over the
      last 4 years dealt with issues of medical ethics. The annual rate of basic
      research articles was relatively stable. Conversely, the rate of 'view points,'
      notably regarding ethics aspects, increased dramatically in 2004. The issues
      regarding the donor were found in 26% of the articles, the psychological echo on
      the recipient in 53% of the articles but in 81% of the medical ethics papers, the
      immunologic risks in 81% of the articles, the surgical risks in 66% of the
      articles, socio-cultural aspects in 34% of the articles, and expense problems in
      5% of the articles. CONCLUSION: Psychological, immunologic, and surgical risks
      are the problems addressed most in the literature. Cost, donor, social, and
      cultural aspects are least addressed. There is a lack of hard data in the
      literature regarding those problems.

PMID- 16631487
TI  - Using distraction osteogenesis for repositioning the multiple dental implants
      retained premaxilla with autogenous bone graft and keratinized palatal mucosa
      graft vestibuloplasty in a trauma patient: report of a case.

PMID- 16631488
TI  - Surgical technique for achieving implant parallelism and measurement of the
      discrepancy in panoramic radiograph.
AB  - PURPOSE: This article describes a surgical technique for achieving implant
      placement parallelism and presents an equation concept to predict the bone depth
      available for implant placement by measuring the discrepancy of the panoramic
      radiograph compared with a clinical situation in cases in which a wide edentulous
      area is present. MATERIALS AND METHODS: A surgical template with tube technique
      in combination with measurement of the vertical dimension of the mandible bone
      available for implant placement was used to treat 2 patients in whom 7 and 3
      implants, respectively, were inserted in the lower and upper jaws. RESULTS: All
      implants were successfully implanted into their reliable positions. In regard to
      the position of an important area such as the inferior alveolar nerve and
      maxillary sinus, this predictive equation can provide an extra margin of
      security. CONCLUSION: A partial denture surgical template technique with tube
      technique using a Coen's drill guide in combination with a mathematical equation
      to find the clinical-radiographic discrepancy can be used as an alternative
      method in placement guidance of dental implant insertions and its fixed
      prosthetic treatment planning in a wide edentulous area.

PMID- 16631489
TI  - Zygomatic implants--protocol for immediate occlusal loading: a preliminary
      report.
AB  - PURPOSE: To investigate the modified protocol for immediate occlusal loading of
      the zygomatic implants and to report the preliminary results of this modified
      protocol. MATERIALS AND METHODS: Four male patients and 1 female patient with
      edentulous maxillae were consecutively treated with the zygomatic implants under
      general anesthesia. All 5 patients were examined by computed tomography and
      investigated by the SimPlant software (Materialise NV, Leuven, Belgium). Based on
      the virtual surgical plans, mucosa-supported surgical guides were manufactured by
      rapid prototyping technique before implant operation. Instead of making a Le Fort
      I Osteotomy incision or a crestal incision, buccal vestibular incision was used
      to expose the surgical site for the zygomatic implant osteotomy and placement.
      Three patients had their remaining upper teeth removed on the same day as implant
      placement. One patient had undergone simultaneous placement of upper and lower
      implants followed by immediate loading. The immediate loading protocol was a 2
      stage method using a customized provisional fixed prosthesis. RESULTS: Ten
      zygomatic implants and 20 normal implants were installed in these 5 patients.
      These 5 patients were reviewed regularly for 6 to 10 months after immediate
      loading. The zygomatic implants were considered to be successful when they were
      asymptomatic with no clinical mobility and no sign of infection. All the
      zygomatic implants and normal implants were investigated individually after
      removing the provisional prosthesis and were found to be clinically stable and
      asymptomatic. CONCLUSION: According to our observation, immediate occlusal
      loading of the zygomatic implants has a very good potential for success, as much
      as immediate occlusal loading of normal dental implants. The surgical placement
      of the zygomatic implant is simplified and facilitated by making use of the
      computer-assisted planning and the rapid-prototyping surgical guides.

PMID- 16631490
TI  - Placement of dental implants in irradiated bone: the case for using hyperbaric
      oxygen.

PMID- 16631491
TI  - Treatment of the irradiated patient with dental implants: the case against
      hyperbaric oxygen treatment.

PMID- 16631492
TI  - Treatment of a ranula using an Er,Cr:YSGG laser.
AB  - A ranula is an extravasational cyst arising from the sublingual gland. The "cyst"
      cavity does not have an epithelial lining, and because of this is notoriously
      difficult to eliminate. Usual treatment requires complete excision of the
      sublingual gland, exteriorizing the gland through establishment of a secondary
      ductal structure by placement of a long-term indwelling catheter, or packing, all
      requiring patient compliance. Unroofing alone is often followed by recurrence via
      resealing or closure with formation of a new roof. The accompanying scarring and
      damage to additional ducts may also result in recurrence. Combining unroofing
      with a technique that would prevent resealing of the remaining portion, scarify
      the base of the ranula to eliminate residual glandular acini, and be more
      comfortable and non-interfering with the daily activity of the patient, is an
      acceptable object of treatment of a ranula. The use of a water-based laser system
      to accomplish these goals appears to be a desirable and simple method.

PMID- 16631493
TI  - Traditional Chinese medicines and bone formation--a review.
AB  - Traditional Chinese medicines have been used in the Chinese population for the
      treatment of bone diseases and to promote bone healing for thousands of years.
      Some traditional Chinese medicines have shown therapeutic effects on fracture
      healing in clinical and animal studies. It is reasonable, therefore, to postulate
      that some traditional Chinese medicines somehow affect the process of bone
      metabolism and bone formation. The aim of this article is to review the bone
      forming effect of various traditional Chinese medicines.

PMID- 16631494
TI  - Case for tort reform in medical malpractice.
AB  - Under tort law, injured parties have the basic right to seek indemnity for
      wrongful injury, including injury from medical malpractice. Unfortunately, the
      present system is associated with many undesirable secondary effects, including
      problems of patient access to care, excessive testing or overtreatment, and
      undertreatment due to doctors' fear of malpractice. Nationwide, there are
      innumerable cases of doctors abandoning obstetrical or other high risk practices,
      or migrating away from states with less friendly tort laws. The California MICRA
      legislation of 1976 is often cited as a model for tort reform, but even this
      model legislation may be insufficient to restore a beleaguered trust between
      medical providers and their patients. Several key research studies suggest that
      the jury system fails to fairly and reliably compensate injured patients, and
      fails to deter or discipline errant doctors. To adequately meet the common needs
      of patients and health care providers, there must be an appropriate emphasis on
      aggressive risk management, quality improvement, patient safety, professional
      oversight, and responsible insurance underwriting. Moreover, there must be a
      systemic improvement of the current tort system as it pertains to medical
      malpractice. Although incremental reforms at the state level are slowly occurring
      and should certainly be supported, a greater reward may ultimately stem from more
      radical restructuring to a system of medical tribunals.

PMID- 16631495
TI  - Unilateral mandibulomaxillar synostosis as a single anomaly in a newborn.

PMID- 16631496
TI  - The use of endoscopy for management of bilateral sagittal split complications.

PMID- 16631497
TI  - The neodymium:YAG laser in the treatment of traumatic tattoo: a case report.

PMID- 16631498
TI  - Distraction of Le Fort II osteotomy by intraoral distractor: a case report.

PMID- 16631499
TI  - Early diagnosis and successful management of atypical invasive Aspergillus
      sinusitis in a hematopoietic cell transplant patient: a case report.

PMID- 16631500
TI  - Papillary cystadenocarcinoma arising in the floor of the mouth: report of a case.

PMID- 16631501
TI  - Minimally invasive fracture treatment with cannulated lag screws in intracapsular
      fractures of the condyle.
AB  - PURPOSE: We examined the use of cannulated lag screw osteosynthesis for the
      treatment of fractures of the mandibular condylar head in providing a high
      quality durable fixation, while at the same time reducing the trauma necessary
      for an open approach to the fracture site. PATIENTS AND METHODS: A preauricular
      approach was used for exposure, reduction, and osteosynthesis in 5 cases of type
      B condylar fractures. A cannulated screw system was used that allowed optimum
      placement of the self-cutting cannulated lag screw following insertion of a
      guiding wire and using clinical control to ensure its correct position. The
      joints were submitted to functional exercises immediately following surgery and
      postoperative radiologic, axiographic, and clinical follow-ups were performed.
      RESULTS: Radiologic follow-up revealed correct reduction and fixation in all 5
      cases. Axiographic and clinical follow-up showed an initial limitation, but
      normal mobility of the condyles was achieved within 3 months postoperatively,
      with a maximum mouth opening of 41.2 +/- 9.4 mm after 6 months. There were no
      occlusal disturbances, no trismus, no lateral deviations of the mandible, and no
      nerve lesions. Intraoperatively, the method applied shortened the time necessary
      for and simplified the procedure of reduction and osteosynthesis. CONCLUSION: By
      using a cannulated lag screw, it was shown that the major factor in the extent of
      the trauma relating to surgical access was the reduction of the fracture
      fragments. The method ensured stable fixation of the fracture with a minimum of
      osteosynthesis material, while reducing the operative time. In combination with
      intraoperative imaging techniques it can also successfully be applied to other
      fractures in maxillofacial surgery.

PMID- 16631502
TI  - Infrequent surgical events: a resident's wish or a private practitioner's
      nightmare?

PMID- 16631503
TI  - Vulnerable Plaque Symposium, Boston, Massachusetts, USA, October 2003.

PMID- 16631504
TI  - Epilogue: what do clinicians expect from imagers?

PMID- 16631505
TI  - Pathology of the vulnerable plaque.
AB  - The majority of patients with acute coronary syndromes (ACS) present with
      unstable angina, acute myocardial infarction, and sudden coronary death. The most
      common cause of coronary thrombosis is plaque rupture followed by plaque erosion,
      whereas calcified nodule is infrequent. If advances in coronary disease are to
      occur, it is important to recognize the precursor lesion of ACS. Of the three
      types of coronary thrombosis, a precursor lesion for acute rupture has been
      postulated. The non-thrombosed lesion that most resembles the acute plaque
      rupture is the thin cap fibroatheroma (TCFA), which is characterized by a
      necrotic core with an overlying fibrous cap measuring <65 microm, containing rare
      smooth muscle cells but numerous macrophages. Thin cap fibroatheromas are most
      frequently observed in patients dying with acute myocardial infarction and least
      common in plaque erosion. They are most frequently observed in proximal coronary
      arteries, followed by mid and distal major coronary arteries. Vessels
      demonstrating TCFA do not usually show severe narrowing but show positive
      remodeling. In TCFAs the necrotic core length is approximately 2 to 17 mm (mean 8
      mm) and the underlying cross-sectional area narrowing in over 75% of cases is
      <75% (diameter stenosis <50%). The area of the necrotic core in at least 75% of
      cases is < or =3 mm2. These lesions have lesser degree of calcification than
      plaque ruptures. Thin cap fibroatheromas are common in patients with high total
      cholesterol (TC) and high TC/high-density lipoprotein cholesterol ratio, in women
      >50 years, and in those patients with elevated high levels of high sensitivity C
      reactive protein. It has only recently been recognized that their identification
      in living patients might help reduce the incidence of sudden coronary death.

PMID- 16631506
TI  - C-reactive protein and other emerging blood biomarkers to optimize risk
      stratification of vulnerable patients.
AB  - Several emerging plasma biomarkers may ultimately prove useful in risk
      stratification and prognosis of cardiovascular disease. The clinical utility of
      these biomarkers will depend on their ability to provide a reflection of the
      underlying atherosclerotic burden or activity; the ability to provide reliable,
      accurate, and cost-effective information; and the ability to predict future
      events. High-sensitivity C-reactive protein (hs-CRP) fulfills many, if not all,
      of these criteria, and blood levels of hs-CRP are now commonly used in clinical
      practice to improve vascular risk prediction in primary and secondary prevention
      across all levels of low-density lipoprotein-cholesterol (LDL-C), all levels of
      the Framingham Risk Score, and all levels of metabolic syndrome. High-sensitivity
      C-reactive protein may also have clinical relevance as an adjunct to LDL-C for
      both the targeting and monitoring of statin therapy. Accumulating evidence
      suggests that several other selected emerging biomarkers may also potentially
      prove useful in the diagnosis and prognosis of cardiovascular disease.
      Specifically, data are accumulating on the potential clinical utility of
      lipoprotein-associated lipoprotein-associated phospholipase A2, myeloperoxidase,
      oxidized LDL, lipoprotein (a), isoprostanes, and small, dense LDL. This review
      focuses on hs-CRP and these emerging plasma biomarkers, and their potential
      diagnostic and prognostic utility in cardiovascular disease. Plasma biomarkers
      that reflect the clinical potential of atherothrombotic disease may allow more
      precise risk stratification and prognostication in high-risk populations, and
      perhaps earlier diagnosis and intervention in patients at risk for or with occult
      cardiovascular disease.

PMID- 16631507
TI  - New opportunities for identification and reduction of coronary risk: treatment of
      vulnerable patients, arteries, and plaques.
AB  - Advances in the understanding of the role of vulnerable plaque in the causation
      of coronary events, coupled with novel diagnostic and therapeutic approaches,
      create a new opportunity for progress against cardiovascular disease. The
      recognition that non-flow-limiting plaques often produce cardiac events has led
      to the development of invasive and non-invasive methods to identify such plaques
      prospectively. Treatments such as stenting, photodynamic therapy, and novel
      pharmaceutical agents are under consideration as methods to stabilize the
      vulnerable plaques and patients that might be detected, thereby enhancing both
      primary and secondary prevention. Despite the promise of the field, many issues
      remain to be resolved, including the focality versus systemic nature of the
      atherosclerotic process, the ability of detectors to identify the target for
      which they were developed and prove that such a target is linked to clinical
      events, and the efficacy of specific therapy. If vulnerable plaques and patients
      can be successfully identified and treated, there will be immense clinical
      benefits, accompanied by cost savings.

PMID- 16631508
TI  - Imaging vulnerable plaque by ultrasound.
AB  - Diagnostic techniques to identify vulnerable plaques are rapidly evolving.
      Intravascular ultrasound (IVUS) has the ability to detect and localize plaque as
      well as quantitate plaque burden. Recent IVUS studies have suggested that
      patients presenting with acute coronary syndromes have an approximate 25%
      incidence of additional ruptured plaques in arteries other than the culprit
      lesion. The ability of IVUS to detect vulnerable plaques before rupture is
      currently being evaluated by novel techniques. Initially, IVUS was shown to be
      able to characterize plaque broadly as calcified or fibrofatty but was limited in
      its ability to more precisely detect lipid-rich plaques, necrotic cores, and
      thrombus. Recent advances in new applications of IVUS, such as integrated
      backscatter, wavelet analysis, and virtual histology, have focused on evaluating
      and mathematically transforming the radiofrequency signal from ultrasound waves
      into a color-coded representation of plaque characteristics such as lipid,
      fibrous tissue, calcification, and necrotic core. In addition, targeted contrast
      agents, applicable to both intravascular and transthoracic studies, are being
      evaluated in experimental models and aim to highlight specific plaque components,
      such as endothelial adhesion molecules and other plaque components that might be
      useful in targeting vulnerable plaques. These advances pave the way for future
      clinical trials in assessing the ability of such techniques to diagnose
      vulnerable plaques and to assess the effects of both pharmacologic and mechanical
      therapies on plaque characteristics.

PMID- 16631509
TI  - Atherosclerotic plaque characterization by multidetector row computed tomography
      angiography.
AB  - Multidetector row computed tomography angiography (MDCTA) is seen as a potential
      alternative to current imaging methods for the assessment of vessel anatomy and
      atherosclerotic plaque composition/morphology in a great variety of arterial
      beds. Recent advances represented by the increase in gantry speed to <500 ms per
      rotation and in the number of detector rows from 4 to 64, in addition to the
      decrease in slice thickness to submillimetric levels, brought significant
      improvement in diagnostic accuracy by coronary MDCTA. In general, it has a good
      correlation with both intravascular ultrasound (IVUS) and histopathology for
      discrimination between soft, intermediate, and calcified plaques. Plaque area and
      volume tend to be underestimated by 12-detector row MDCTA and overestimated by 16
      detector row MDCTA, but the number of patients studied so far is relatively
      small. However, it seems that 64-detector row MDCTA can measure plaque area and
      volume with greater accuracy. Plaque remodeling is overestimated in small vessels
      by 12-detector row MDCTA, whereas 16- and 64-detector row MDCTA show a good
      correlation with IVUS. Although still under development, the potential of MDCTA
      to characterize atherosclerotic plaque composition as well as to precisely
      determine plaque area, volume, and remodeling in the future is quite promising.

PMID- 16631510
TI  - Role of magnetic resonance and intravascular magnetic resonance in the detection
      of vulnerable plaques.
AB  - Noninvasive magnetic resonance imaging (MRI) has been used to determine vascular
      three-dimensional structure, detect the presence of subclinical atherosclerotic
      disease in high-risk patient subgroups, and optimize and follow therapy in
      individual patients. The outstanding soft-tissue-characterizing capabilities of
      MRI permit depiction of various components of atherothrombotic plaque, including
      lipid, fibrous tissue, calcium, and thrombus formation. However, noninvasive MRI
      visualization of coronary arteries is currently limited by the small size of the
      coronary arteries, the deep arterial location, and arterial motion. The
      combination of MR imaging and molecular probes offers exciting possibilities of
      direct visualization of biologic processes within atherosclerotic tissue. The
      self-contained intravascular MRI probe appears to hold promise in the
      identification of high-risk coronary atherosclerotic lesions with increased
      superficial lipid content.

PMID- 16631511
TI  - Radionuclide imaging for the detection of inflammation in vulnerable plaques.
AB  - Imaging of atheromatous plaques has traditionally centered on assessing the
      degree of luminal stenosis. More recently it has become clear that the vulnerable
      atherosclerotic plaques responsible for the majority of life-threatening
      syndromes are characterized by high numbers of inflammatory cells and proteins.
      This has highlighted the urgent need for suitable imaging techniques that can
      identify and quantify levels of inflammation within atheromatous lesions.
      Positron emission tomography and single-photon emission computed tomography
      imaging hold promise in this regard. Tracer compounds capable of assessing
      macrophage recruitment, foam cell generation, matrix metalloproteinase
      production, macrophage apoptosis, and macrophage metabolism have been developed
      and tested in the carotid and peripheral circulation. The identification of
      inflamed lesions within the coronary circulation, however, remains elusive owing
      to small plaque size, cardiac and respiratory motion, and lack of a suitable
      specific nuclear tracer.

PMID- 16631512
TI  - Plaque characterization with optical coherence tomography.
AB  - The identification of unstable plaque is central in risk-stratifying patients for
      acute coronary events. Optical coherence tomography (OCT) is a recently
      introduced imaging modality that has shown considerable promise for the
      identification of high-risk plaques. Advantages of OCT include its high
      resolution (4 to 20 microm), high data acquisition rate, small and inexpensive
      guidewires/catheters, and ability to be combined with adjuvant optical
      techniques. This article summarizes the current state of intravascular OCT
      imaging, focusing on potential markers of instability and current limitations.

PMID- 16631513
TI  - Pathogenesis of atherosclerosis.
AB  - Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease of medium
      sized and large arteries fuelled by lipids. Endothelial cells, leukocytes, and
      intimal smooth muscle cells are the major players in the development of this
      disease. The most devastating consequences of atherosclerosis, such as heart
      attack and stroke, are caused by superimposed thrombosis. Therefore, the vital
      question is not why atherosclerosis develops but rather why atherosclerosis,
      after years of indolent growth, suddenly becomes complicated with luminal
      thrombosis. If thrombosis-prone plaques could be detected and thrombosis averted,
      atherosclerosis would be a much more benign disease. Approximately 76% of all
      fatal coronary thrombi are precipitated by plaque rupture. Plaque rupture is a
      more frequent cause of coronary thrombosis in men (approximately 80%) than in
      women (approximately 60%). Ruptured plaques are characterized by a large lipid
      rich core, a thin fibrous cap that contains few smooth muscle cells and many
      macrophages, angiogenesis, adventitial inflammation, and outward remodeling.
      Plaque rupture is the most common cause of coronary thrombosis. Ruptured plaques
      and, by inference, rupture-prone plaques have characteristic pathoanatomical
      features that might be useful for their detection in vivo by imaging. This
      article describes the pathogenesis of atherosclerosis, how it begets thrombosis,
      and the possibility to detect thrombosis-prone plaques and prevent heart attack.

PMID- 16631514
TI  - Intracoronary thermography for detection of high-risk vulnerable plaques.
AB  - Up to two-thirds of acute myocardial infarctions develop at sites of culprit
      lesions without a significant stenosis. New imaging techniques are needed to
      identify those lesions with an increased risk of developing an acute complication
      in the near future. Inflammation is a hallmark feature of these vulnerable/high
      risk plaques. We have shown that inflamed atherosclerotic plaques are hot and
      their surface temperature correlates with an increased number of macrophages and
      decreased fibrous-cap thickness. Multiple animal and human experiments have shown
      that temperature heterogeneity correlates with arterial inflammation in vivo.
      Several coronary temperature mapping catheters are currently being developed and
      studied. These thermography methods can be used in the future to detect
      vulnerable plaques, potentially to determine patients' prognosis, and to study
      the plaque-stabilizing effects of different medications.

PMID- 16631515
TI  - Intravascular palpography for vulnerable plaque assessment.
AB  - Palpography assesses the local mechanical properties of tissue using the
      deformation caused by the intraluminal pressure. The technique was validated in
      vitro using diseased human coronary and femoral arteries. Especially between
      fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012)
      was found. Additionally, the predictive value to identify the vulnerable plaque
      was investigated. A high-strain region at the lumen vessel wall boundary has 88%
      sensitivity and 89% specificity for identifying these plaques. In vivo, the
      technique is validated in an atherosclerotic Yucatan minipig animal model. This
      study also revealed higher strain values in fatty than in fibrous plaques (p <
      0.001). The presence of a high-strain region at the lumen-plaque interface has a
      high predictive value to identify macrophages. Patient studies revealed high
      strain values (1% to 2%) in noncalcified plaques. Calcified material showed low
      strain values (0% to 0.2%). With the development of three-dimensional
      palpography, identification of weak spots over the full length of a coronary
      artery becomes available. Patients with myocardial infarction or unstable angina
      have more high-strain spots in their coronary arteries than patients with stable
      angina. In conclusion, intravascular palpography is a unique tool to assess
      lesion composition and vulnerability. Three-dimensional palpography provides a
      technique that may develop into a clinically available tool for decision making
      to treat hemodynamically nonsignificant lesions by identifying vulnerable
      plaques. The clinical utility of this technique is yet to be determined, and more
      investigation is needed.

PMID- 16631516
TI  - Near-infrared spectroscopy for the detection of vulnerable coronary artery
      plaques.
AB  - This review describes efforts to use near-infrared (NIR) spectroscopy to identify
      chemical components of coronary artery plaques as a means to assess
      vulnerability. Near-infrared spectroscopy has been well-validated by the physical
      sciences as a method to characterize chemical composition of various bio
      materials and could be ideal to detect vulnerable coronary plaques in patients.
      Recent studies in aortic and coronary artery autopsy specimens have confirmed the
      ability of the technique to identify lipid-rich thin-cap fibroatheromas through
      blood. A catheter-based system has been developed to address the challenges-of
      access to the coronary artery, blood, motion, and the need to scan-that must be
      overcome for use in patients. Initial clinical experience in six patients with
      stable angina demonstrates that high-quality NIR spectra can be safely obtained.
      Additional studies are planned to validate the ability of the technique to
      identify lipid-rich coronary artery plaques and ultimately link chemical
      characterization with subsequent occurrence of an acute coronary syndrome.

PMID- 16631517
TI  - Intravascular radiation detectors for the detection of vulnerable atheroma.
AB  - An intravascular catheter was developed to identify inflammation in coronary
      atheroma. Inflammation in atheroma is associated with large numbers of
      macrophages. These cells have increased metabolism, increased expression of
      chemotactic receptors, and a high frequency of apoptosis-associated
      phosphatidylserine expression. Each of these parameters can be identified in vivo
      using specific radiolabeled agents: metabolism can be identified with 18F
      fluorodeoxyglucose (FDG), receptor expression with 99mTc monocyte chemotactic
      peptide-1, and apoptosis with 99mTc annexin V. The locally increased
      concentration of these tracers is readily demonstrable in experimental lesions by
      ex vivo autoradiography; however, the small lesion size makes it difficult to
      identify atheroma in the coronaries with conventional imaging equipment. In
      contrast, with a radiation-sensitive catheter, optimized to sense charged
      particle rather than gamma or x-radiation, specific lesions could be identified
      and localized. Charged particle radiation is emitted as a byproduct of nearly all
      radioactive decay but is typically most abundant in radionuclides that decay by
      beta emission (either positrons or negatrons). Prototype catheters, using a
      plastic scintillator mated to an optical fiber, have been tested in the
      laboratory with the positron-emitting radiopharmaceutical 18FDG. The catheter had
      sufficient sensitivity to detect lesions concentrating nanocurie concentrations
      of 18FDG. Ex vivo experiments in apo-e-/- mice confirmed the ability of the
      catheter to detect 18FDG in aortic lesions. These feasibility studies demonstrate
      the sensitivity of a beta-sensitive catheter system. Additional mechanical
      refinements are needed to optimize the system in anticipation of in vivo animal
      studies.

PMID- 16631518
TI  - gamma-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2
      signaling in rat epithelial type II cells.
AB  - gamma-Glutamyl transpeptidase (GGT) plays key roles in glutathione homeostasis
      and metabolism of glutathione S-conjugates. Rat GGT is transcribed via five
      tandemly arranged promoters into seven transcripts. The transcription of mRNA V
      is controlled by promoter 5. Previously we found that GGT mRNA V-2 was
      responsible for the induction of GGT in rat alveolar epithelial cells by 4
      hydroxynonenal (HNE). In the current study, the underlying mechanism was
      investigated. Reporter deletion and mutation analysis demonstrated that an
      electrophile-response element (EpRE) in the proximal region of GGT promoter 5
      (GP5) was responsible for the basal- and HNE-induced promoter activity. Gel-shift
      assays showed an increased binding activity of GP5 EpRE after HNE exposure. The
      nuclear content of NF-E2-related factor 2 (Nrf2) was significantly increased by
      HNE. The recruitment of Nrf2 to GP5 EpRE after HNE treatment was demonstrated by
      supershift and chromatin immunoprecipitation assays. The tissue expression
      pattern of GGT mRNA V was previously unknown. Using polymerase chain reaction, we
      found that GGT mRNA V-2 was expressed in many tissues in rat. Taken together, GGT
      mRNA V-2 is widely expressed in rat tissues and its basal and HNE-induced
      expression is mediated through EpRE/Nrf2 signaling.

PMID- 16631519
TI  - Chemotherapy induces an increase in coenzyme Q10 levels in cancer cell lines.
AB  - Free radicals have been implicated in the action of many chemotherapeutic drugs.
      Here we tested the hypothesis that camptothecin and other chemotherapeutic drugs,
      such as etoposide, doxorubicin, and methotrexate, induce an increase in coenzyme
      Q(10) levels as part of the antioxidant defense against free radical production
      under these anticancer treatments in cancer cell lines. Chemotherapy treatment
      induced both free radical production and an increase in coenzyme Q(10) levels in
      all the cancer cell lines tested. Reduced coenzyme Q(10) form levels were
      particularly enhanced. Coenzyme Q(10)-increased levels were associated with up
      regulation of COQ genes expression, involved in coenzyme Q(10) biosynthesis. At
      the translational level, COQ7 protein expression levels were also increased.
      Furthermore, coenzyme Q(10) biosynthesis inhibition blocked camptothecin-induced
      coenzyme Q(10) increase, and enhanced camptothecin cytotoxicity. Our findings
      suggest that coenzyme Q(10) increase is implicated in the cellular defense under
      chemotherapy treatment and may contribute to cell survival.

PMID- 16631520
TI  - Intracellular distribution of oxidized proteins and proteasome in HT22 cells
      during oxidative stress.
AB  - The production of free radicals and the resulting oxidative damage of cellular
      structures are always connected with the formation of oxidized proteins. The 20S
      proteasome is responsible for recognition and degradation of oxidatively damaged
      proteins. No detailed studies on the intracellular distribution of oxidized
      proteins during oxidative stress and on the distribution of the proteasome have
      been performed until now. Therefore, we used immunocytochemical methods to
      measure protein carbonyls, a form of protein oxidation products, and proteasome
      distribution within cells. Both immunocytochemical methods of measurement are
      semiquantitative and the load of oxidized proteins is increased after various
      oxidative stresses explored, with the highest increase in the perinuclear region
      of the cell. Distribution of the proteasome and the total protein content
      revealed the highest concentration of both in the nucleus. No redistribution of
      the proteasome during oxidative stress occurs. The normalized ratio of protein
      carbonyls to protein content was formed, indicating the highest concentration of
      oxidized proteins in the cytosolic region near the cell membrane. By forming the
      protein oxidation-to-proteasome ratio it was concluded that the highest load of
      oxidized proteins to the proteasome takes place in the cytosol, independent of
      the oxidant explored.

PMID- 16631521
TI  - Heme oxygenase-1 contributes to the cytoprotection of alpha-lipoic acid via
      activation of p44/42 mitogen-activated protein kinase in vascular smooth muscle
      cells.
AB  - Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen
      species (ROS) and regenerates or recycles endogenous antioxidants. ALA has
      recently been reported to protect against oxidative injury in various disease
      processes. The aim of this study was to investigate whether the antioxidant
      effect of ALA is mediated by the induction of heme oxygenase (HO)-1 in rat aortic
      smooth muscle cells (A10 cells). ALA significantly induced HO-1 expression
      accompanied by an increase in HO activity in A10 cells. Pretreatment with ALA
      increased the resistance of A10 cells to hydrogen-peroxide-induced oxidant
      stress. This protection of ALA was abrogated in the presence of the HO inhibitor
      zinc protoporphyrin IX. ALA significantly increased ROS, and this effect was
      blocked by N-acetyl-cysteine, which also inhibited ALA-induced activation of
      p44/42 mitogen-activated protein kinase (MAPK) and AP-1, HO-1 expression, and HO
      activity. These results suggest that ALA induces HO-1 expression through the
      production of ROS and subsequent activation of the p44/42 MAPK pathway and AP-1
      in vascular smooth muscle cells. This study demonstrated that ALA increases the
      expression of HO-1, a critical cytoprotective molecule, and identified a novel
      pleiotropic effect of ALA on cardiovascular protection.

PMID- 16631522
TI  - Nitric oxide-induced resistance to lethal photooxidative damage in a breast tumor
      cell line.
AB  - The long-term effects of nitric oxide (NO) on cell susceptibility to photodynamic
      killing have been studied, using a human breast tumor line (COH-BR1).
      Subconfluent cells were exposed to a nonlethal dose of spermine NONOate (SPNO,
      0.2 mM) and 20 h later were metabolically sensitized with protoporphyrin IX
      (PpIX) by incubating with 5-aminolevulinic acid. PpIX overproduced in
      mitochondria was allowed to diffuse to peripheral sites, including plasma
      membrane, after which a photooxidative challenge was imposed. Active (but not
      decomposed) SPNO made cells substantially more resistant to necrotic photokilling
      than non-SPNO-treated controls. A similar response to a tert-butyl hydroperoxide
      challenge was observed. Hyperresistance was detected approximately 8 h post-SPNO,
      maximized after approximately 20 h, and reflected diminished oxidant
      accumulation, as determined with 2',7'-dichlorofluorescein. Intracellular free
      iron determined with the fluorescent probe calcein rose to approximately 160% of
      the control level 6 h after SPNO, but declined to approximately 70% after 24 h.
      Immunoblot analyses revealed a rapid early (approximately 2 h post-NO) increase
      in heme oxygenase-1 level, followed by a gradual (4-20 h post-NO) increase in
      ferritin. Upregulation of these proteins is consistent with a cytoprotective
      mechanism involving mobilization of "signaling" iron. Preactivated RAW 264.7
      macrophages on microporous inserts also induced a long-term photoresistance in
      underlying PpIX-sensitized COH-BR1 cells. This response was abolished by L-NAME,
      indicating that NO from induced nitric oxide synthase was involved. The NO
      effects described are entirely novel in the context of photooxidative stress and
      provide new insights into how NO might affect antitumor photodynamic therapy
      (PDT).

PMID- 16631523
TI  - Carbon monoxide, oxidative stress, and mitochondrial permeability pore
      transition.
AB  - The cellular effects of carbon monoxide (CO) are produced primarily by CO binding
      to iron or other transition metals, which may also promote prooxidant activities
      of the more reactive gases, oxygen and nitric oxide. We tested the hypothesis
      that prooxidant effects of CO deregulate the calcium-dependent mitochondrial pore
      transition (MPT), which disrupts membrane potential and releases apoptogenic
      proteins. Rats were exposed to either CO (50 ppm) or hypobaric hypoxia (HH) for
      1, 3, or 7 days, and liver mitochondria harvested to study protein expression and
      sensitivity to MPT by calcium and oxidants. Both exposures induced hypoxia
      sensitive protein expression: hypoxia-inducible factor 1alpha (HIF-1alpha), heme
      oxygenase-1 (HO-1), and manganese SOD (SOD2), but SOD2 induction was greater by
      CO than by HH, especially at 7 days. Relative to HH, CO also caused significant
      early mitochondrial oxidative and nitrosative stress shown by decreases in
      GSH/GSSG and increases in protein 3-nitrotyrosine (3-NT) and protein mixed
      disulfide formation. This altered MPT sensitivity to calcium through an effect on
      the "S-site," causing loss of pore protection by adenine nucleotides. By 7 days,
      despite continued CO, nitrosative stress decreased and adenine nucleotide
      protection was restored to preexposure levels. This is the first evidence of
      functional mitochondrial pore stress caused by CO independently of its hypoxic
      effect, as well as a compensatory response exemplifying a mitochondrial phenotype
      shift. The implications are that cellular CO can activate or deactivate
      mitochondria for initiation of apoptosis in vivo.

PMID- 16631524
TI  - Dinitrosyl-iron triggers apoptosis in Jurkat cells despite overexpression of Bcl
      2.
AB  - Cells expressing the cytokine-inducible NO synthase are known to trigger
      apoptosis in neighboring cells. Paramagnetic dinitrosyl nonheme iron complexes
      (DNIC) were found in tumor tissue about 40 years ago; however, the role of these
      NO(+)-bearing species is not completely understood. In the human Jurkat leukemia
      cell line, the application of the model complex DNIC-thiosulfate (50-200 microM)
      induced apoptosis (defined by phosphatidylserine externalization) in a
      concentration- and time-dependent manner. In Jurkat cells, the pan-caspase
      inhibitor, zVADfmk (50 microM), and/or stable transfection of antiapoptotic
      protein, Bcl-2, was unable to afford protection against DNIC-induced apoptosis.
      The membrane-impermeable metal chelator, N-methyl-D-glucamine dithiocarbamate
      (MGD; 200 microM), in the presence of DNIC significantly increased apoptosis, but
      had no effect on its own. Electron paramagnetic resonance studies showed that MGD
      led to rapid transformation of the extracellular DNIC into the stable impermeable
      NO-Fe-MGD complex and to a burst-type release of nitrosonium (NO(+)) equivalents
      in the extracellular space. These results suggest that in Jurkat cells, DNIC
      thiosulfate induces Bcl-2- and caspase-independent apoptosis, which is probably
      secondary to local nitrosative stress at the cell surface. We hypothesize that
      the local release of nonheme Fe-NO species by activated macrophages may play a
      role in the killing of malignant cells that have high Bcl-2 levels.

PMID- 16631525
TI  - The novel antioxidant 3-O-caffeoyl-1-methylquinic acid induces Nrf2-dependent
      phase II detoxifying genes and alters intracellular glutathione redox.
AB  - Induction of detoxifying phase II genes by chemopreventive agents represents a
      coordinated protective response against oxidative stress and neoplastic effects
      of carcinogens. We have earlier shown that a novel antioxidant from the bamboo
      leaves constituent 3-O-caffeoyl-1-methylquinic acid (MCGA3) induces heme
      oxygenase-1 (HO-1) and protects endothelial cells from ROS-induced endothelial
      injury. The purpose of this study was to elucidate the induction mechanism of HO
      1 and other phase II genes by MCGA3 in human umbilical vascular endothelial cells
      (HUVECs). Using Northern blotting and RT-PCR, we found that treatment of HUVECs
      with MCGA3 increased, in a dose and time-dependent manner, steady-state mRNA
      levels of the selected phase II genes including HO-1, ferritin, gamma
      glutamylcysteine lygase, glutathione reductase, and glutathione transferase,
      which were dependent on Nrf2 nuclear translocation. The observed phase II gene
      induction by MCGA3 was found to be associated with MCGA3-mediated cytoprotective
      activity, ROS-scavenging potency, and the increase in the cellular levels of both
      reduced (GSH) and oxidized glutathione (GSSG). Interestingly, exposure to MCGA3
      resulted in a decreased ratio of GSH/GSSG, which was negatively related with mRNA
      level of phase II genes. By employing N-acetylcysteine and GSH biosynthetic
      enzyme inhibitors as well as prooxidants, hemin and H(2)O(2), we show that a
      decreased intracellular GSH/GSSG homeostasis, at least in part, may be involved
      in the MCGA3-mediated phase II gene induction and Nrf2 translocation, although
      the attenuation of HO-1 expression with SP 600125 supports a partial involvement
      of JNK signaling.

PMID- 16631526
TI  - Redox-sensitive target detection in gibberellic acid-induced barley aleurone
      layer.
AB  - Reactive oxygen species (ROS) are involved in redox regulation by their capacity
      to reversibly oxidize cysteine residues. This regulation is used by cells to
      modulate and integrate different responses to extracellular stimuli. In the
      barley (Hordeum vulgare L.) aleurone layer, gibberellic acid (GA(3)) is perceived
      at the plasma membrane and induces the synthesis and secretion of alpha-amylase.
      All aleurone membrane systems participate in the elaboration of this response.
      During these events, ROS are generated as a by-product from intense lipid
      metabolism. Therefore, we hypothesized that redox regulation may be operating in
      the GA(3)-induced response. To test this hypothesis, we measured if GA(3)
      treatment induced changes in the redox state of aleurone membrane-associated
      proteins. Membrane proteins with sulfhydryl and disulfide groups were isolated
      from reduced and in situ NEM-alkylated microsomal fractions, respectively. Each
      fraction was enriched by thiol-affinity chromatography and separated by two
      dimensional electrophoresis. The in vivo redox state of each membrane protein
      present in GA(3)-treated and -untreated tissue was determined. Results showed
      that GA(3) induced the reduced state in 17 constitutive proteins and the oxidized
      state in another 5. These data indicate that redox changes occur in membrane
      proteins after GA(3) signaling in the aleurone layer.

PMID- 16631527
TI  - Mechanisms of nitric-oxide-induced increase of free cytosolic Ca2+ concentration
      in Nicotiana plumbaginifolia cells.
AB  - In this study, we investigated a role for nitric oxide (NO) in mediating the
      elevation of the free cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in plants
      using Nicotiana plumbaginifolia cells expressing the Ca(2+) reporter apoaequorin.
      Hyperosmotic stress induced a fast increase of [Ca(2+)](cyt) which was strongly
      reduced by pretreating cell suspensions with the NO scavenger carboxy PTIO,
      indicating that NO mediates [Ca(2+)](cyt) changes in plant cells challenged by
      abiotic stress. Accordingly, treatment of transgenic N. plumbaginifolia cells
      with the NO donor diethylamine NONOate was followed by a transient increase of
      [Ca(2+)](cyt) sensitive to plasma membrane Ca(2+) channel inhibitors and
      antagonist of cyclic ADP ribose. We provided evidence that NO might activate
      plasma membrane Ca(2+) channels by inducing a rapid and transient plasma membrane
      depolarization. Furthermore, NO-induced elevation of [Ca(2+)](cyt) was suppressed
      by the kinase inhibitor staurosporine, suggesting that NO enhances [Ca(2+)](cyt)
      by promoting phosphorylation-dependent events. This result was further supported
      by the demonstration that the NO donor induced the activation of a 42-kDa protein
      kinase which belongs to SnRK2 families and corresponds to Nicotiana tabacum
      osmotic-stress-activated protein kinase (NtOSAK). Interestingly, NtOSAK was
      activated in response to hyperosmotic stress through a NO-dependent process,
      supporting the hypothesis that NO also promotes protein kinase activation during
      physiological processes.

PMID- 16631528
TI  - The superoxide dismutase inhibitor diethyldithiocarbamate has antagonistic
      effects on apoptosis by triggering both cytochrome c release and caspase
      inhibition.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and etoposide both trigger a large and
      rapid production of reactive oxygen species (ROS) in HeLa cells. This occurs
      before translocations of the proapoptotic Bax and cytochrome c proteins, the loss
      of mitochondrial membrane potential (DeltaPsim), and apoptosis. We have used
      diethyldithiocarbamate (DDC), a well-known inhibitor of Cu, Zn superoxide
      dismutase to study the role of ROS in this system. We report that DDC strongly
      inhibits caspase activation, loss of DeltaPsim, and cell death induced by TNF
      alpha or etoposide. Surprisingly, DDC does not inhibit Bax and cytochrome c
      translocations. On the contrary, we have observed that DDC can trigger the
      translocations of these proteins by itself, without altering DeltaPsim. Here, we
      report that DDC has at least two antagonistic apoptosis regulation functions.
      First, DDC triggers ROS-dependent Bax and cytochrome c translocations, which are
      potentially proapoptotic, and second, DDC inhibits caspase activation and
      activity, loss of DeltaPsim, and cell death, in a ROS-independent manner. Our
      results suggest an interesting model in which ROS-dependent Bax and cytochrome c
      translocations can be studied without interference from later apoptotic events.

PMID- 16631529
TI  - The yeast cytosolic thioredoxins are involved in the regulation of methionine
      sulfoxide reductase A.
AB  - Previously we have shown that the binding complex formation of methionine
      sulfoxide reductase A (msrA) promoter and calcium phospholipid binding protein
      (CPBP) enhances msrA transcription and expression. The msrA promoter-CPBP-binding
      complex (PmsrA-CPBP) formation was similar in Deltatrx1, Deltatrx2, and Deltatrx3
      yeast strains and their control, with or without exposure to H(2)O(2). In
      Deltatrx1/Deltatrx2 double mutant the PmsrA-CPBP was similar to its parent
      strain, following exposure to H(2)O(2) for 30 min. However, a late-onset loss of
      PmsrA-CPBP binding activity occurred following exposure to H(2)O(2) for 24 hours.
      Hence, it was inferred that both Trx1 and Trx2 are involved in the PmsrA-CPBP
      formation during prolonged oxidative stress conditions. In addition, the survival
      rate of the Deltatrx1Delta/trx2 double mutant was approximately 10% of its parent
      strain when exposed to H(2)O(2.) The MsrA activity was obliterated in
      Deltatrx1/Deltatrx2 and Deltatrx1 strains and remained intact in the Deltatrx2
      and Deltatrx3 strains. The msrA mRNA level in Deltatrx1 was significantly reduced
      in comparison to that of its control, slightly reduced in Deltatrx2, and
      unchanged in Deltatrx3, respectively. It is suggested that under normal growth
      conditions Trx1 is essential for msrA transcription and activity. Moreover,
      following long-term oxidative stress conditions, Trx1 and Trx2 appear to promote
      PmsrA-CPBP-binding activity and cell survival.

PMID- 16631530
TI  - Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated
      gastric mucosal injury and curcumin protects it by preventing peroxidase
      inactivation and scavenging reactive oxygen.
AB  - We have investigated the mechanism of indomethacin-induced gastric ulcer caused
      by reactive oxygen species (ROS) and the gastroprotective effect of curcumin
      thereon. Curcumin dose-dependently blocks indomethacin-induced gastric lesions,
      showing 82% protection at 25 mg/kg. Indomethacin-induced oxidative damage by ROS
      as shown by increased lipid peroxidation and thiol depletion is almost completely
      blocked by curcumin. Indomethacin causes nearly fivefold increase in hydroxyl
      radical (()OH) and significant inactivation of gastric mucosal peroxidase to
      elevate endogenous H(2)O(2) and H(2)O(2)-derived ()OH, which is prevented by
      curcumin. In vitro studies indicate that indomethacin inactivates peroxidase
      irreversibly only in presence of H(2)O(2) by acting as a suicidal substrate. 5,5
      Dimethyl-pyrroline-N-oxide (DMPO) protects the peroxidase, indicating involvement
      of indomethacin radical in the inactivation. Indomethacin radical was also
      detected in the peroxidase-indomethacin-H(2)O(2) system as DMPO adduct (a(N) = 15
      G, a(beta)(H) = 16 G) by electron spin resonance spectroscopy. Curcumin protects
      the peroxidase in a concentration-dependent manner and consumes H(2)O(2) for its
      oxidation as a suitable substrate of the peroxidase, thereby blocking
      indomethacin oxidation. Curcumin can also scavenge ()OH in vitro. We suggest that
      curcumin protects gastric damage by efficient removal of H(2)O(2) and H(2)O(2) 
      derived ()OH by preventing peroxidase inactivation by indomethacin.

PMID- 16631531
TI  - The nitroxide Tempol modulates anthracycline resistance in breast cancer cells.
AB  - The occurrence of multidrug resistance (MDR) is the major obstacle to successful
      anthracycline-based cancer chemotherapy. In the present study, we assessed the
      effects of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, TPL), a
      piperidine nitroxide with growth-inhibitory properties in tumor cell lines, on a
      number of molecular mechanisms involved in the resistance of human breast
      adenocarcinoma cell lines to doxorubicin (DOX). Cytotoxicity studies in MCF-7
      wildtype and their MDR variant MCF-7 Adr(R) cells showed a synergistic effect
      between TPL and DOX when exposure to TPL preceded or was simultaneous with DOX
      treatment in MCF-7 Adr(R) cells. This effect of TPL seems to be due in part to
      its ability to increase peroxide levels and to deplete cellular glutathione
      pools. In addition, TPL increased DOX accumulation in MCF-7 Adr(R) cells by
      interfering with P-glycoprotein-mediated DOX efflux, as evidenced using a
      specific antibody that recognizes the active form of the protein. TPL was also
      found to affect the expression levels of proteins involved in response to drug
      treatment (e.g., p53, bcl2, bax, p21). Taken together, our results indicate that
      TPL is a potential new agent that may improve the clinical effect of DOX in
      tumors exhibiting a MDR phenotype.

PMID- 16631532
TI  - Metallothionein alleviates cardiac dysfunction in streptozotocin-induced
      diabetes: role of Ca2+ cycling proteins, NADPH oxidase, poly(ADP-Ribose)
      polymerase and myosin heavy chain isozyme.
AB  - Diabetic cardiomyopathy contributes to high morbidity and mortality in diabetic
      populations. It is manifested by compromised ventricular contraction and
      prolonged relaxation attributable to multiple causative factors including
      oxidative stress. This study was designed to examine the effect of cardiac
      overexpression of the heavy metal scavenger metallothionein (MT) on cardiac
      contractile function, intracellular Ca(2+) cycling proteins, stress-activated
      signaling molecules and the myosin heavy chain (MHC) isozyme in diabetes. Adult
      male wild-type (FVB) and MT transgenic mice were made diabetic by a single
      injection of streptozotocin (STZ). Contractile properties were evaluated in
      cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to
      relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dL/dt)
      and intracellular Ca(2+) fluorescence. Diabetes significantly depressed PS, +/
      dL/dt, prolonged TPS, TR(90) and intracellular Ca(2+) clearing, elevated resting
      intracellular Ca(2+), reduced caffeine-induced sarcoplasmic reticulum Ca(2+)
      release and dampened stress tolerance at high stimulus frequencies. MT itself
      exhibited little effect on myocyte mechanics but it significantly alleviated STZ
      induced myocyte contractile dysfunctions. Diabetes enhanced expression of the
      AT(1) receptor, phospholamban, the p47(phox) NADPH oxidase subunit and poly(ADP
      ribose) polymerase (PARP), depressed the level of SERCA2a, Na(+)-Ca(2+) exchanger
      and triggered a beta-MHC isozyme switch. All of these STZ-induced alterations
      with the exception of depressed SERCA2a and enhanced phospholamban were
      reconciled by MT. Collectively, these data suggest a beneficial effect of MT in
      the therapeutics of diabetic cardiomyopathy, possibly through a mechanism related
      to NADPH oxidase, PARP and MHC isozyme switch.

PMID- 16631533
TI  - Reactive oxygen species attenuate nitric-oxide-mediated hypoxia-inducible factor
      1alpha stabilization.
AB  - Tissue hypoxia/ischemia are major pathophysiological determinants. Conditions of
      decreased oxygen availability provoke accumulation and activation of hypoxia
      inducible factor-1 (HIF-1). Recent reports demonstrate a crucial role of HIF-1
      for inflammatory events. Regulation of hypoxic responses by the inflammatory
      mediators nitric oxide (NO) and reactive oxygen species (ROS) is believed to be
      of pathophysiolgical relevance. It is reported that hypoxic stabilization of HIF
      1alpha can be antagonized by NO due to its ability to attenuate mitochondrial
      electron transport. Likely, the formation of ROS could contribute to this effect.
      As conflicting results emerged from several studies showing either decreased or
      increased ROS production during hypoxia, we used experiments mimicking hypoxic
      intracellular ROS changes by using the redox cycling agent 2,3-dimethoxy-1,4
      naphthoquinone (DMNQ), which generates superoxide inside cells. Treatment of
      A549, HEK293, HepG2, and COS cells with DMNQ resulted in a concentration
      dependent raise in ROS which correlated with HIF-1alpha accumulation. By using a
      HIF-1alpha-von Hippel-Lindau tumor suppressor protein binding assay, we show that
      ROS produced by DMNQ impaired prolyl hydroxylase activity. When HIF-1alpha is
      stabilized by NO, low concentrations of DMNQ (<1 microM) revealed no effect,
      intermediate concentrations of 1 to 40 microM DMNQ attenuated HIF-1alpha
      accumulation and higher concentrations of DMNQ promoted HIF-1alpha stability.
      Attenuation of NO-induced HIF-1alpha stability regulation by ROS was mediated by
      an active proteasomal degradation pathway. In conclusion, we propose that
      scavenging of NO by ROS and vice versa attenuate HIF-1alpha accumulation in a
      concentration-dependent manner. This is important to fully elucidate HIF-1alpha
      regulation under inflammatory conditions.

PMID- 16631534
TI  - Critical role of endothelial cell-derived nitric oxide synthase in sickle cell
      disease-induced microvascular dysfunction.
AB  - Superoxide, which can limit nitric oxide bioavailability, has been implicated in
      blood cell-vessel wall interactions observed in sickle cell transgenic (beta(S))
      mice. Here we report that nonselective chemical inhibition of nitric oxide
      synthase isoforms dramatically reduces the enhanced leukocyte and platelet
      adhesion normally observed in cerebral venules of beta(S) mice. Although genetic
      deficiency of vascular wall inducible nitric oxide synthase does not alter
      adhesion responses in beta(S) mice, a significant attenuation is noted in beta(S)
      mice with vascular wall endothelial nitric oxide synthase (eNOS) deficiency,
      while the adhesion responses are exacerbated when eNOS is overexpressed in
      microvessels. The eNOS-mediated enhancement of blood cell adhesion is reversible
      by pretreatment with sepiapterin (which generates the eNOS cofactor
      tetrahydrobiopterin) or polyethyleneglycol-superoxide dismutase, implicating a
      role for eNOS-dependent superoxide production. These findings suggest that an
      imbalance between eNOS-derived nitric oxide and superoxide, both generated by the
      vessel wall, is critical to the proinflammatory and prothrombogenic phenotype
      that is assumed by the microvasculature in sickle cell disease.

PMID- 16631536
TI  - Increased levels of F2-isoprostanes following aneurysmal subarachnoid hemorrhage
      in humans.
AB  - Subarachnoid hemorrhage (SAH) resulting from aneurysmal rupture is the major
      cause of nontraumatic SAH. We hypothesized that oxidative stress could be
      increased following aneurysmal SAH due to hemoglobin release and ischemia
      reperfusion injury and that may further contribute to poor outcome. We collected
      plasma and cerebrospinal fluid (CSF) samples from 11 non-SAH controls and 15
      aneurysmal SAH patients for up to 10 days after surgery and investigated status
      of oxidative stress in patients. Results showed that mean or peak levels of F(2)
      isoprostanes (F(2)-IsoPs), a specific marker of lipid peroxidation, and total
      nitrate/nitrite, metabolites of nitric oxide and peroxynitrite, in CSF and plasma
      were significantly higher in SAH patients than in controls. First-day levels were
      also higher in CSF, but not in plasma, in SAH patients. Moreover, mean and peak
      levels of CSF F(2)-IsoPs were positively correlated with poor outcome or severity
      of clinical conditions in patients. Furthermore, levels of retinol, delta
      tocopherol, beta+gamma-tocopherol, lutein, beta-carotene, and coenzyme Q(10) in
      plasma were significantly lower in SAH patients than in controls. Our results
      indicate that oxidative damage may play important roles in the severity and
      complications of aneurysmal SAH and suggest that means to suppress lipid
      peroxidation may be beneficial in improving the outcome of aneurysmal SAH.

PMID- 16631535
TI  - Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose)
      polymerase activation in diabetic rat kidney and high-glucose-exposed human
      mesangial cells.
AB  - Both increased aldose reductase (AR) activity and oxidative/nitrosative stress
      have been implicated in the pathogenesis of diabetic nephropathy, but the
      relation between the two factors remains a subject of debate. This study
      evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose)
      polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed
      human mesangial cells. In animal experiments, control (C) and streptozotocin
      diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg
      kg(-1) day(-1)) for 6 weeks starting from induction of diabetes. Glucose,
      sorbitol, and fructose concentrations were significantly increased in the renal
      cortex of D vs C (p < 0.01 for all three comparisons), and sorbitol pathway
      intermediate, but not glucose, accumulation, was completely prevented in D + F. F
      at least partially prevented diabetes-induced increase in kidney weight as well
      as nitrotyrosine (NT, a marker of peroxynitrite-induced injury and nitrosative
      stress), and poly(ADP-ribose) (a marker of PARP activation) accumulation,
      assessed by both immunohistochemistry and Western blot analysis, in glomerular
      and tubular compartments of the renal cortex. In vitro studies revealed the
      presence of both AR and PARP-1 in human mesangial cells, and none of these two
      variables were affected by high glucose or F treatment. Nitrosylated and poly(ADP
      ribosyl)ated proteins (Western blot analysis) accumulated in cells cultured in 30
      mM D-glucose (vs 5.55 mM glucose, p < 0.01), but not in cells cultured in 30 mM L
      glucose or 30 mM D-glucose plus 10 microM F. AR inhibition counteracts
      nitrosative stress and PARP activation in the diabetic renal cortex and high
      glucose-exposed human mesangial cells. These findings reveal new beneficial
      properties of the AR inhibitor F and provide the rationale for detailed studies
      of F on diabetic nephropathy.

PMID- 16631537
TI  - Alcohol consumption is directly associated with circulating oxidized low-density
      lipoprotein.
AB  - Findings on the association of alcohol consumption and oxidation of low-density
      lipoprotein (LDL), which is thought to play a crucial role in the generation of
      atherosclerotic lesion, are inconsistent. The aim of the present study was to
      investigate the association of total alcohol consumption and type of alcoholic
      beverage with circulating plasma LDL oxidation. This cross-sectional study
      included data of circulating oxidized LDL (ox-LDL) from a subpopulation of 587
      men and women enrolled in a population-based survey conducted in 2000 in Girona
      (Spain). Multivariate analysis was performed to describe the independent
      association of alcohol consumption and ox-LDL. Increasing alcohol consumption was
      associated with high in vivo ox-LDL levels in the present population. The
      consumption of 10 g of alcohol was associated with an increase of 2.40 U/L of ox
      LDL (p = 0.002). Adjustment for dietary variables, leisure-time physical
      activity, educational level, smoking, LDL-cholesterol, high-density lipoprotein
      cholesterol, glycemia, triglycerides, diabetes, body mass index, waist
      circumference, and systolic and diastolic blood pressures only slightly modified
      this association (p = 0.003). In this full adjusted model the consumption of 10 g
      of alcohol per day was associated with an increase of 2.11 U/L of ox-LDL.
      Consumption of wine (ml/day) was associated with increasing ox-LDL levels (p =
      0.029), however, attenuated after controlling for alcohol. No significant
      relationship of ox-LDL with alcohol-independent consumption of wine, beer, and
      spirits was observed. Alcohol consumption was independently and directly
      associated with circulating ox-LDL in the present population.

PMID- 16631538
TI  - The future should not look like the past.

PMID- 16631539
TI  - Deadly "paleoviruses": a bioweapon Pandora's box?

PMID- 16631540
TI  - Cytotoxic T-cell immunity as a target for influenza vaccines.

PMID- 16631541
TI  - Influenza pandemic plans: what about displaced populations?

PMID- 16631542
TI  - Phage in the time of cholera.

PMID- 16631544
TI  - Continuous intravenous administration of antibiotics.

PMID- 16631545
TI  - Man bites dog.

PMID- 16631547
TI  - Influenza vaccination for health-care workers who work with elderly people in
      institutions: a systematic review.
AB  - Our aim was to review the evidence of efficacy and effectiveness of influenza
      vaccination of health-care workers in reducing cases of influenza-like illness,
      influenza, complications from influenza, death from influenza, and death from all
      causes among the elderly people they care for in institutions. We searched 11
      electronic databases in any language and identified two cluster-randomised
      controlled trials with moderate risk of bias and one cohort study at high risk of
      bias that addressed our questions. Staff vaccination had a significant effect on
      influenza-like illness (vaccine effectiveness [VE] 86%, 95% CI 40-97%) only when
      patients were vaccinated too. If patients were not vaccinated, staff immunisation
      had no effect. Vaccinating health-care workers did not appear efficacious against
      influenza (RR 0.87, 95% CI 0.46-1.63). There was no significant effect of
      vaccination on lower respiratory tract infections: (RR 0.70, 95% CI 0.41-1.20).
      Deaths from pneumonia were significantly reduced (VE 39%, 95% CI 2-62%), as were
      deaths from all causes (VE 40%, 95% CI 27-50%). These findings must be
      interpreted in the light of possible selection, performance, attrition, and
      detection biases.

PMID- 16631548
TI  - Immunological recovery and antiretroviral therapy in HIV-1 infection.
AB  - Potent antiretroviral therapy has dramatically improved the prognosis of patients
      infected with HIV-1. Primary and secondary prophylaxis against Pneumocystis
      carinii, Mycobacterium avium, cytomegalovirus, and other pathogens can be
      discontinued safely once CD4 cell counts have increased beyond pathogen-specific
      thresholds. Approximately one-third of individuals receiving antiretroviral
      therapy will not reach CD4 cell counts above 500 cells per muL after 5 years
      despite continuous suppression of plasma HIV-1 RNA. Whether this failure
      represents a risk factor for the long-term incidence of opportunistic diseases-
      eg, tuberculosis or malignancies--remains uncertain. We describe the time course
      of CD4 cell concentrations in patients whose plasma HIV-1 RNA is durably
      suppressed by antiretroviral therapy, in patients with incomplete suppression of
      plasma HIV-1 RNA, and during treatment interruptions. In addition, immune
      reconstitution disease, an inflammatory syndrome associated with immunological
      recovery occurring days to weeks after the start of antiretroviral therapy, is
      briefly described.

PMID- 16631549
TI  - Mycobacterium ulcerans infection: control, diagnosis, and treatment.
AB  - The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third
      most common mycobacterial disease after tuberculosis and leprosy and mainly
      affects remote rural African communities. Although the disease is known to be
      linked to contaminated water, the mode of transmission is not yet understood,
      which makes it difficult to propose control interventions. The disease is usually
      detected in its later stages, when it has caused substantial damage and
      disability. Surgery remains the treatment of choice. Although easy and effective
      in the early stages of the disease, treatment requires extended excisions and
      long hospitalisation for the advanced forms of the disease. Currently, no
      antibiotic treatment has proven effective for all forms of M ulcerans infection
      and research into a new vaccine is urgently needed. While the scientific
      community works on developing non-invasive and rapid diagnostic tools, the
      governments of endemic countries should implement active case finding and health
      education strategies in their affected communities to detect the disease in its
      early stages. We review the diagnosis, treatment, and control of Buruli ulcer and
      list priorities for research and development.

PMID- 16631550
TI  - Severe dengue: the need for new case definitions.
AB  - Dengue fever imposes a societal burden that is difficult to measure because of
      the disease's non-specific symptoms and the lack of easily applied case
      definitions for its more severe manifestations. An efficacy trial of a
      tetravalent vaccine is expected in the near future, but only one of the severe
      dengue syndromes-the continuum of dengue haemorrhagic fever and dengue shock
      syndrome-is well defined. One of the results of the focus on dengue haemorrhagic
      fever is the false perception of low disease burden in the Americas, which is an
      obstacle to the mobilisation of political and economic resources to fight the
      disease. Three improvements are necessary to standardise the dengue haemorrhagic
      fever definition and to allow it to do well in different populations: (1)
      redefine the threshold for thrombocytopenia, (2) clarify the standard practice
      and value of the tourniquet test, and (3) incorporate a criterion to measure
      intravenous fluid replacement. In addition, for an accurate estimation of dengue
      burden, locally appropriate definitions of severe dengue must be devised and
      standardised so they will be considered valid in the global research community.

PMID- 16631551
TI  - Interactions between influenza and bacterial respiratory pathogens: implications
      for pandemic preparedness.
AB  - It is commonly believed that the clinical and epidemiological characteristics of
      the next influenza pandemic will mimic those of the 1918 pandemic. Determinative
      beliefs regarding the 1918 pandemic include that infections were expressed as
      primary viral pneumonias and/or acute respiratory distress syndrome, that
      pandemic-related deaths were the end states of the natural progression of disease
      caused by the pandemic strain, and that bacterial superinfections caused
      relatively fewer deaths in 1918 than in subsequent pandemics. In turn, response
      plans are focused on developing and/or increasing inventories of a strain
      specific vaccine, antivirals, intensive care beds, mechanical ventilators, and so
      on. Yet, there is strong and consistent evidence of epidemiologically and
      clinically important interactions between influenza and secondary bacterial
      respiratory pathogens, including during the 1918 pandemic. Countermeasures (eg,
      vaccination against pneumococcal and meningococcal disease before a pandemic;
      mass uses of antibiotic(s) with broad spectrums of activity against common
      bacterial respiratory pathogens during local epidemics) designed to prevent or
      mitigate the effects of influenza-bacterial interactions should be major focuses
      of pandemic-related research, prevention, and response planning.

PMID- 16631552
TI  - Cytomegalovirus in an AIDS patient.

PMID- 16631553
TI  - A missionary with a swelling on her hip.

PMID- 16631554
TI  - Microvascular soft tissue reconstruction of the digits.
AB  - INTRODUCTION: Composite tissue loss to digits following trauma may require flap
      coverage. Local reconstruction techniques are popular but can result in a
      functional limitation at the donor site. Small free flaps though complex, may
      provide a superior alternative. METHOD: We retrospectively reviewed the case
      notes of all patients who had a small free flap to a digit following trauma. The
      time period was 4 years (2000-2004). Sixteen patients with 18 digital free flaps
      were identified. These comprised of 10 venous flow-through flaps, one lateral arm
      flap, one great toe to thumb pulp transfer, three first web space flaps from the
      foot, one medial plantar flap and two free posterior interosseous flaps. All 16
      patients were invited for clinical review at an out-patients clinic. Ten patients
      (11 flaps) attended follow-up. Standardised assessment of outcome in terms of
      scar quality at both the recipient and donor sites, sensibility, range of motion
      and function of the hand was completed. RESULTS: Overall the average follow-up
      period was 14 months, with 16 out of 18 flaps surviving. Of the patients that
      attended for clinical review, the majority recovered excellent function of the
      hand (quick-DASH--av. 5.7) with satisfactory aesthetics, minimal pain or
      limitations in range of motion. The flaps were all soft and durable. Ten flaps
      recovered protective but not discriminative sensation (only one flap was
      innervated). The three patients whose donor site was the first-web space of the
      foot developed significant hypertrophic scarring. CONCLUSION: Small free flaps
      provide an acceptable method of reconstructing digital defects. Venous flow
      through flaps provided the best overall results in this series. The donor site
      for first-web space flaps is probably unacceptable.

PMID- 16631555
TI  - Unique superiority of microsurgical repair technique with its functional and
      aesthetic outcomes in ring avulsion injuries.
AB  - Although ring avulsion injuries are not common, when they do occur their
      management is still a challenging problem in reconstructive surgery. In this
      report, we present our microsurgical experiences with Kay's class III and IV ring
      avulsion injuries. A total of six patients with ring avulsion injuries were
      operated on between 2000 and 2004. Three patients were in class III with
      inadequacy of both arterial and venous circulation, and the remaining three were
      in class IV. The study consisted of four male and two female patients whose ages
      ranged from 23 to 43 (mean age 32). Average ischaemic time was 2.2 h (range 1-4
      h). The ring finger was involved in all cases and microsurgical repair was
      performed using axillary block anaesthesia. The bone was detached at the level of
      the distal interphalangeal joint and soft tissues at the proximal phalanx level
      with the preserved proximal interphalangeal joint and flexor digitorum
      superficialis tendon in all cases. Because the zone of injury is more extensive,
      we debrided the avulsed digital artery over a long distance, and used long
      interpositional vein grafts radically in all patients. Venous drainage was
      accomplished by performing at least two vein anastomoses using vein grafts when
      necessary. Both digital nerves were repaired primarily after debridement. Results
      indicated that microsurgical repair had a success rate of 100%. The authors
      conclude that microsurgical reconstruction of ring avulsion injuries with intact
      proximal interphalangeal joint and flexor digitorum superficialis tendon yields
      superior results, both functionally and aesthetically, even in complete
      amputation.

PMID- 16631556
TI  - Modifying integra as a regeneration template in deep tissue planes.
AB  - Contour defects resulting in deformity caused by lack of tissue can be improved
      by conventional surgery using autologous tissue, but there is always a donor site
      morbidity. Integra has been available since the early 1980's for use in acute
      burns and more recently in reconstruction. It has been shown histologically to
      act as a tissue regeneration template. The regenerated dermis is buried under an
      autologous thin split-skin graft. In this study, the principle of burying Integra
      (without the silicone layer) has been applied to deep tissue defects in 12
      reconstructive cases. Such regenerated tissues survive at least 3 years after
      burying. Modification to the technique to avoid visible edges are being
      developed.

PMID- 16631557
TI  - Hypoglossal nerve transfer in obstetric brachial plexus palsy.
AB  - A cost-benefit analysis was performed of hypoglossal nerve transfer in six
      patients with obstetric brachial palsy taking into account the factors donor site
      morbidity and extent of recovery. Hypoglossal nerve transfer was employed in four
      children for elbow flexion only; in two patients for elbow flexion as well as for
      elbow extension. The transfer was part of an extended brachial plexus
      reconstruction for treatment of obstetric brachial plexus palsy. After a mean
      post-operative interval of 52 months (SD+/-8.1), two professional speech
      therapists investigated late donor site morbidity by analyzing elementary and
      communicative functions. The functional result for the arm was assessed using the
      Mallet scale and by performing a physical examination. Following hypoglossal
      nerve transfer, early donor site morbidity was significant causing great anxiety
      in the parents. Late donor site morbidity consisted of serious oral problems in a
      number of the children. They also showed clear associated movements in the arm
      during mouth/tongue activity. Recovery of powerful volitional elbow flexion was
      achieved in four cases only. We do not believe that the sacrifice of such an
      important function as exerted by the hypoglossal nerve is balanced by the gain
      demonstrated in our series.

PMID- 16631558
TI  - Is there increased risk of local and in-transit recurrence following sentinel
      lymph node biopsy?
AB  - Recent publications have suggested that sentinel lymph node biopsy (SLNB) and
      completion lymphadenectomy (CLND) increase the rate of local and in-transit
      disease up to 23% in sentinel node positive group of patients with cutaneous
      melanoma. This retrospective study combined the data from two national centres on
      local and in-transit disease in 972 melanoma patients who underwent SLNB
      procedure over 6.5 years period. In total, 77 patients (7.9%) developed loco
      regional recurrence: 41 (4.2%) local recurrence only and 36 patients (3.7%) in
      transit metastases during a mean follow-up of 42 months. Patients with positive
      sentinel lymph node were three times more likely to develop loco-regional
      metastases than those with no nodal disease (17 vs. 5.6%). Over one third of all
      recurrences developed following excision of thick (Breslow thickness over 4mm)
      primary tumours. In both centres age and Breslow thickness were found to be
      significantly higher in the recurrence group (p<0.001 for both). This study
      revealed a strong association between increased risk of loco-regional metastases
      and aggressive tumour biology and adverse patients factors. No conclusive
      evidence was found to support an increased incidence in patients undergoing SLNB
      and CLND compared to that published for patients undergoing wide local excision
      alone.

PMID- 16631559
TI  - The elevation of the constructed auricle with a temporoparietal fascial flap
      wrapping a resorbable plate.
AB  - During the second stage reconstruction of the auricle in patients with microtia,
      we modified Nagata's method and two technical improvements were possible. After
      the implanted auricle was separated from the bed, we harvested the
      temporoparietal fascial flap through helical rim incision instead of incising the
      temporal scalp. So the surgical scar over the temporal region was avoided.
      Thereafter, a costal cartilage wedge was carved and grafted to the posterior
      aspect of the conchal region to get a firm projection. But in cases of
      unavailable costal cartilage wedge graft, we used a resorbable plate composed of
      polylactic and polyglycolic acid as a substitute for the former so that we could
      create firm elevation and sufficient ear projection. Between June 2002 and May
      2004, 28 patients underwent this operation with the temporoparietal fascial flap
      and resorbable plating system. There was no complication resulting from our
      technique. It was possible to create firm elevation and good frontal projection
      even if there was no available cartilage wedge. Additionally, by harvesting the
      temporoparietal fascia through helical rim incision, we avoid creating additional
      scars on the scalp.

PMID- 16631560
TI  - Thromboembolic prophylaxis in plastic surgery a 12-year follow up in the UK.
AB  - Potentially fatal thromboembolic events prevail post-operatively despite the
      widespread availability of proven methods of prophylaxis. In 1992 Dujon et al
      published an article which reviewed thromboembolic prophylaxis methods of
      Consultant Plastic Surgeons in the UK and Ireland. Our follow up study surveyed
      all current Consultant B.A.P.S members using a modified postal questionnaire to
      assess practice nationwide. Our conclusions were drawn from comparisons made
      between the two populations some twelve years apart. Our results show a dramatic
      change from the previous findings. Since 1992 86% of respondents have developed a
      set prophylaxis protocol (compared to 19%). The use of low molecular weight
      heparin has drastically increased by 24% to 76%, the use of flow-tron boots (or
      similar) has increased by 22% to 68%, the use of TED stockings has increased by
      12% to 83%, the use of multi-modality prophylaxis has increased by 27% to 79% Our
      results demonstrate a definite shift towards multi-modal thromboembolic
      prophylaxis, possibly due to increased awareness of available technologies and
      subsequent reduction in costs.

PMID- 16631561
TI  - Flexor tendon rupture 55 years following a wrist laceration.
AB  - Flexor tendon rupture at the wrist or palm is rare. We present a case of index
      flexor digitorum profundus rupture at the level of the wrist associated with the
      site of a laceration 55 years earlier. Associated pathology included a large
      neuroma-in-continuity of the median nerve and adhesions involving the flexor
      digitorum superficialis tendons. The rupture was treated by tenodesis to the
      relatively unaffected flexor digitorum profundus to the adjacent long finger.

PMID- 16631562
TI  - Guillain-Barre syndrome following facial bone fracture.
AB  - Guillain-Barre syndrome (GBS) is an inflammatory disorder of the peripheral
      nerves and nerve roots characterised by lymphocytes and macrophage infiltration
      and myelin destruction. Two-thirds of cases of GBS emerge from viral or bacterial
      infection. GBS following facial bone fracture is rare. This article discusses a
      case of classical GBS following facial bone fracture and its correlative
      mechanism. The association of GBS with head injury per se is not well recognised.
      This case highlights the possibility of GBS following facial bone fracture and
      indicates that medical staff should be alerted to the association.

PMID- 16631563
TI  - Squamous cell carcinoma of penis presenting as groin metastasis 3 years before
      the primary.
AB  - A 78-year-old patient who developed bilateral inguinal node metastatic squamous
      cell carcinoma, more than 3 years before the primary penile carcinoma declared
      itself, is presented. An exhaustive multispeciality search for the primary
      including a circumcision proved fruitless. A review of the relevant literature is
      summarised.

PMID- 16631564
TI  - Is pregnancy contraindicated following free TRAM breast reconstruction?
AB  - There are reports of patients having normal full term pregnancies following
      pedicled transverse rectus abdominis myocutaneous (TRAM) flap breast
      reconstruction. These are individual cases and there is only limited published
      evidence to support the safety of pregnancy following surgery of this nature.
      Little is known about the effects of pregnancy after free tissue transfer,
      therefore it has been difficult to advise patients, in this situation, what the
      recommended course of action should be. A report of pregnancy following free TRAM
      flap breast reconstruction is presented with a review of relevant literature in
      an attempt to clarify this issue and improve the consent process. We conclude
      that TRAM flap breast reconstruction is not an obstacle to normal pregnancy and
      delivery. Patients need to be guided through the potential risks to their health
      if they should become pregnant, before reconstruction takes place. Obstetric and
      Oncological Specialists, as part of the multi-disciplinary setting, need to be
      involved early in pregnancy to further inform and counsel these patients.

PMID- 16631565
TI  - United Kingdom and Ireland Plastic Surgery Units publication rates 2003-2005.

PMID- 16631566
TI  - Marjolin's ulcer (correction of ucler) at a Nigerian hospital (1993-2003).

PMID- 16631567
TI  - Macromolecular crowding.

PMID- 16631568
TI  - Membrane biophysics.

PMID- 16631569
TI  - The path of DNA in the kinetochore.

PMID- 16631570
TI  - Gravity bias in the interpretation of biological motion by inexperienced chicks.

PMID- 16631571
TI  - Life history shapes gene expression in salmonids.

PMID- 16631572
TI  - Motor control: the importance of stiffness.
AB  - An octopus brings food grasped by a tentacle to its mouth by bending the tentacle
      around a joint formed by stiffened distal and proximal tentacle muscles, and thus
      may use motor control strategies analogous to those in animals with articulated
      limbs.

PMID- 16631573
TI  - Evolution: the plastic transcriptome.
AB  - Studies across a wide range of species point to a surprising degree of plasticity
      in the transcriptional states that organisms can adopt, suggesting that organisms
      often respond to environmental challenges through wholesale reprogramming of
      their gene expression.

PMID- 16631574
TI  - Chromatin remodeling: RSC Motors along the DNA.
AB  - Single-molecule experiments show that the chromatin-remodeling complex RSC, a
      member of the SNF2 ATPase family, induces formation of a negatively supercoiled
      DNA loop by active translocation.

PMID- 16631575
TI  - Linguistic relativity: does language help or hinder perception?
AB  - A recent study has explored the interplay between language and perception through
      the brain's visual pathways. The results suggest an influence of linguistic
      categories on the speed of colour discrimination.

PMID- 16631576
TI  - Animal behaviour: old world monkeys build new world order.
AB  - New experimental evidence shows that policing behaviour by dominant monkeys
      stabilizes and integrates macaque societies.

PMID- 16631577
TI  - Visual motion: homing in on small target detectors.
AB  - Tracking moving targets is essential for animals that pursue prey or
      conspecifics. Recent studies in male and female hoverflies have described classes
      of neurons that detect the movements of small targets against a moving background
      but the mechanisms generating their responses remain unclear.

PMID- 16631578
TI  - Language processing: the neural basis of nouns and verbs.
AB  - A new study of the functional anatomy of noun and verb production suggests an
      important role for semantic representations in the cortical processing of these
      two distinct grammatical classes.

PMID- 16631579
TI  - DNA repair: DNA polymerase zeta and Rev1 break in.
AB  - DNA polymerase zeta and Rev1 play key roles in replication past DNA lesions. New
      work shows that the yeast checkpoint kinase Mec1 recruits a complex consisting of
      polymerase zeta and Rev1 to DNA double-strand breaks. This study highlights the
      role of polymerases that mediate translesion synthesis in the response to DNA
      double-strand breaks.

PMID- 16631580
TI  - HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore
      microtubules in the vicinity of chromosomes.
AB  - BACKGROUND: Formation of a bipolar mitotic spindle in somatic cells requires the
      cooperation of two assembly pathways, one based on kinetochore capture by
      centrosomal microtubules, the other on RanGTP-mediated microtubule organization
      in the vicinity of chromosomes. How RanGTP regulates kinetochore-microtubule (K
      fiber) formation is not presently understood. RESULTS: Here we identify the
      mitotic spindle protein HURP as a novel target of RanGTP. We show that HURP is a
      direct cargo of importin beta and that in interphase cells, it shuttles between
      cytoplasm and nucleus. During mitosis, HURP localizes predominantly to
      kinetochore microtubules in the vicinity of chromosomes. Overexpression of
      importin beta or RanT24N (resulting in low RanGTP) negatively regulates its
      spindle localization, whereas overexpression of RanQ69L (mimicking high RanGTP)
      enhances HURP association with the spindle. Thus, RanGTP levels control HURP
      localization to the mitotic spindle in vivo, a conclusion supported by the
      analysis of tsBN2 cells (mutant in RCC1). Upon depletion of HURP, K-fiber
      stabilization is impaired and chromosome congression is delayed. Nevertheless,
      cells eventually align their chromosomes, progress into anaphase, and exit
      mitosis. HURP is able to bundle microtubules and, in vitro, this function is
      abolished upon complex formation with importin beta and regulated by Ran. These
      data indicate that HURP stabilizes K-fibers by virtue of its ability to bind and
      bundle microtubules. CONCLUSIONS: Our study identifies HURP as a novel component
      of the Ran-importin beta-regulated spindle assembly pathway, supporting the
      conclusion that K-fiber formation and stabilization involves both the centrosome
      dependent microtubule search and capture mechanism and the RanGTP pathway.

PMID- 16631581
TI  - HURP is part of a Ran-dependent complex involved in spindle formation.
AB  - BACKGROUND: GTP-loaded Ran induces the assembly of microtubules into aster-like
      and spindle-like structures in Xenopus egg extract. The microtubule-associated
      protein (MAP), TPX2, can mediate Ran's role in aster formation, but factors
      responsible for the transition from aster-like to spindle-like structures have
      not been described. RESULTS: Here we identify a complex that is required for the
      conversion of aster-like to spindle-like structures. The complex consists of two
      characterized MAPs (TPX2, XMAP215), a plus end-directed motor (Eg5), a mitotic
      kinase (Aurora A), and HURP, a protein associated with hepatocellular carcinoma.
      Formation and function of the complex is dependent on Aurora A activity. HURP
      protein was further characterized and shown to bind microtubules and affect their
      organization both in vitro and in vivo. In egg extract, anti-HURP antibodies
      disrupt the formation of both Ran-dependent and chromatin and centrosome-induced
      spindles. HURP is also required for the proper formation and function of mitotic
      spindles in HeLa cells. CONCLUSIONS: HURP is a new and essential component of the
      mitotic apparatus. HURP acts as part of a multicomponent complex that affects the
      growth or stability of spindle MTs and is required for spindle MT organization.

PMID- 16631582
TI  - In vitro FRAP identifies the minimal requirements for Mad2 kinetochore dynamics.
AB  - BACKGROUND: Mad1 and Mad2 are constituents of the spindle-assembly checkpoint, a
      device coupling the loss of sister-chromatid cohesion at anaphase to the
      completion of microtubule attachment of the sister chromatids at metaphase.
      Fluorescence recovery after photobleaching (FRAP) revealed that the interaction
      of cytosolic Mad2 with kinetochores is highly dynamic, suggesting a mechanism of
      catalytic activation of Mad2 at kinetochores followed by its release in a complex
      with Cdc20. The recruitment of cytosolic Mad2 to kinetochores has been attributed
      to a stable receptor composed of a distinct pool of Mad2 tightly bound to Mad1.
      Whether specifically this interaction accounts for the kinetochore dynamics of
      Mad2 is currently unknown. RESULTS: To gain a precise molecular understanding of
      the interaction of Mad2 with kinetochores, we reconstituted the putative Mad2
      kinetochore receptor and developed a kinetochore recruitment assay with purified
      components. When analyzed by FRAP in vitro, this system faithfully reproduced the
      previously described in vivo dynamics of Mad2, providing an unequivocal molecular
      account of the interaction of Mad2 with kinetochores. Using the same approach, we
      dissected the mechanism of action of p31(comet), a spindle-assembly checkpoint
      inhibitor. CONCLUSIONS: In vitro FRAP is a widely applicable approach to
      dissecting the molecular bases of the interaction of a macromolecule with an
      insoluble cellular scaffold. The combination of in vitro fluorescence recovery
      after photobleaching with additional fluorescence-based assays in vitro can be
      used to unveil mechanism, stoichiometry, and kinetic parameters of a
      macromolecular interaction, all of which are important for modeling protein
      interaction networks.

PMID- 16631583
TI  - Octopuses use a human-like strategy to control precise point-to-point arm
      movements.
AB  - One of the key problems in motor control is mastering or reducing the number of
      degrees of freedom (DOFs) through coordination. This problem is especially
      prominent with hyper-redundant limbs such as the extremely flexible arm of the
      octopus. Several strategies for simplifying these control problems have been
      suggested for human point-to-point arm movements. Despite the evolutionary gap
      and morphological differences, humans and octopuses evolved similar strategies
      when fetching food to the mouth. To achieve this precise point-to-point-task,
      octopus arms generate a quasi-articulated structure based on three dynamic
      joints. A rotational movement around these joints brings the object to the mouth
      . Here, we describe a peripheral neural mechanism-two waves of muscle activation
      propagate toward each other, and their collision point sets the medial-joint
      location. This is a remarkably simple mechanism for adjusting the length of the
      segments according to where the object is grasped. Furthermore, similar to
      certain human arm movements, kinematic invariants were observed at the joint
      level rather than at the end-effector level, suggesting intrinsic control
      coordination. The evolutionary convergence to similar geometrical and kinematic
      features suggests that a kinematically constrained articulated limb controlled at
      the level of joint space is the optimal solution for precise point-to-point
      movements.

PMID- 16631584
TI  - C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and
      growth in the germline.
AB  - The molecular pathways that link nutritional cues to developmental programs are
      poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state
      termed "L1 diapause" until food is supplied. However, little is known about what
      signal transduction pathways mediate nutritional status to control arrest and
      initiation of postembryonic development. We report that C. elegans embryonic
      germline precursors undergo G2 arrest with condensed chromosomes and remain
      arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor
      bypasses this arrest, resulting in inappropriate germline growth dependent on the
      AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like
      pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO,
      which is repressed by this pathway, is not required for germline arrest in L1
      diapause. Thus, these findings indicate that quiescence of germline development
      during L1 diapause is not a passive consequence of nutrient deprivation, but
      rather is actively maintained by DAF-18 through a pathway distinct from that
      which regulates longevity and dauer formation.

PMID- 16631585
TI  - DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4
      during C. elegans L1 arrest.
AB  - Development is typically studied as a continuous process under laboratory
      conditions, but wild animals often develop in variable and stressful
      environments. C. elegans larvae hatch in a developmentally arrested state (L1
      arrest) and initiate post-embryonic development only in the presence of food (E.
      coli in lab). In contrast to the well-studied dauer arrest, L1 arrest occurs
      without morphological modification, although larvae in L1 arrest are more
      resistant to environmental stress than developing larvae . Consistent with its
      role in dauer formation and aging, we show that insulin/insulin-like growth
      factor (IGF) signaling regulates L1 arrest. daf-2 insulin/IGF receptor mutants
      have a constitutive-L1-arrest phenotype when fed and extended survival of L1
      arrest when starved. Conversely, daf-16/FOXO mutants have a defective-arrest
      phenotype, failing to arrest development and dying rapidly when starved. We show
      that DAF-16 is required for transcription of the cyclin-dependent kinase
      inhibitor cki-1 in stem cells in response to starvation, accounting for the
      failure of daf-16/FOXO mutants to arrest cell division during L1 arrest. Other
      developmental events such as cell migration, cell fusion, and expression of the
      microRNA lin-4, a temporal regulator of post-embryonic development, are also
      observed in starved daf-16/FOXO mutants. These results suggest that DAF-16/FOXO
      promotes developmental arrest via transcriptional regulation of numerous target
      genes that control various aspects of development.

PMID- 16631586
TI  - The cullin Rtt101p promotes replication fork progression through damaged DNA and
      natural pause sites.
AB  - Accurate and complete DNA replication is fundamental to maintain genome
      integrity. While the mechanisms and underlying machinery required to duplicate
      bulk genomic DNA are beginning to emerge, little is known about how cells
      replicate through damaged areas and special chromosomal regions such as
      telomeres, centromeres, and highly transcribed loci . Here, we have investigated
      the role of the yeast cullin Rtt101p in this process. We show that rtt101Delta
      cells accumulate spontaneous DNA damage and exhibit a G(2)/M delay, even though
      they are fully proficient to detect and repair chromosome breaks. Viability of
      rtt101Delta mutants depends on Rrm3p, a DNA helicase involved in displacing
      proteinaceous complexes at programmed pause sites . Moreover, rtt101Delta cells
      show hyperrecombination at forks arrested at replication fork barriers (RFBs) of
      ribosomal DNA. Finally, rtt101Delta mutants are sensitive to fork arrest induced
      by DNA alkylation, but not by nucleotide depletion. We therefore propose that the
      cullin Rtt101p promotes fork progression through obstacles such as DNA lesions or
      tightly bound protein-DNA complexes via a new mechanism involving ubiquitin
      conjugation.

PMID- 16631587
TI  - An inducible mouse model for PAX2-dependent glomerular disease: insights into a
      complex pathogenesis.
AB  - Pax2 is a transcription factor with important functions during kidney development
      . Ectopic expression of Pax2 in podocytes has been reported in various glomerular
      diseases , but the functional relevance remains unknown. We developed an
      inducible mouse model that allows activation of Pax2 specifically in podocytes.
      Persistent expression of Pax2 did not interfere with the initial differentiation
      of podocytes, but mice ectopically expressing PAX2 developed end-stage renal
      failure soon after birth. Similarly, activation of PAX2 in healthy adult animals
      resulted in renal disease within 3 weeks after podocyte-specific induction of a
      deleter Cre. PAX2 activation caused repression of the podocyte key regulator
      molecule Wt1 and consequently a dramatic reduction of nephrin expression.
      Recruitment of the groucho-related protein TLE4 may be involved in converting
      Pax2 into a transcriptional repressor of Wt1. Finally, treatment of mice with an
      angiotensin-converting enzyme (ACE) inhibitor normalized renal function and
      induced upregulation of the important structural molecule nephrin via a Wt1
      independent pathway. Our data demonstrate the functional significance of PAX2
      reexpression in mature podocytes for the development of glomerular diseases and
      suggest that reactivation of PAX genes in terminally differentiated cells leads
      to a more dedifferentiated phenotype.

PMID- 16631588
TI  - The origin of centrosomes in parthenogenetic hymenopteran insects.
AB  - A longstanding enigma has been the origin of maternal centrosomes that facilitate
      parthenogenetic development in Hymenopteran insects. In young embryos, hundreds
      of microtubule-organizing centers (MTOCs) are assembled completely from maternal
      components. Two of these MTOCs join the female pronucleus to set up the first
      mitotic spindle in unfertilized embryos and drive their development. These MTOCs
      appear to be canonical centrosomes because they contain gamma-tubulin, CP190, and
      centrioles and they undergo duplication. Here, we present evidence that these
      centrosomes originate from accessory nuclei (AN), organelles derived from the
      oocyte nuclear envelope. In the parasitic wasps Nasonia vitripennis and
      Muscidifurax uniraptor, the position and number of AN in mature oocytes
      correspond to the position and number of maternal centrosomes in early embryos.
      These AN also contain high concentrations of gamma-tubulin. In the honeybee, Apis
      mellifera, distinct gamma-tubulin foci are present in each AN. Additionally, the
      Hymenopteran homolog of the Drosophila centrosomal protein Dgrip84 localizes on
      the outer surfaces of AN. These organelles disintegrate in the late oocyte,
      leaving behind small gamma-tubulin foci, which likely seed the formation of
      maternal centrosomes. Accessory nuclei, therefore, may have played a significant
      role in the evolution of haplodiploidy in Hymenopteran insects.

PMID- 16631589
TI  - Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine
      proteases required for Toll activation.
AB  - Unlike mammalian Toll-like Receptors, the Drosophila Toll receptor does not
      interact directly with microbial determinants but is rather activated upon
      binding a cleaved form of the cytokine-like molecule Spatzle (Spz). During the
      immune response, Spz is thought to be processed by secreted serine proteases
      (SPs) present in the hemolymph that are activated by the recognition of gram
      positive bacteria or fungi . In the present study, we have used an in vivo RNAi
      strategy to inactivate 75 distinct Drosophila SP genes. We then screened this
      collection for SPs regulating the activation of the Toll pathway by gram-positive
      bacteria. Here, we report the identification of five novel SPs that function in
      an extracellular pathway linking the recognition proteins GNBP1 and PGRP-SA to
      Spz. Interestingly, four of these genes are also required for Toll activation by
      fungi, while one is specifically associated with signaling in response to gram
      positive bacterial infections. These results demonstrate the existence of a
      common cascade of SPs upstream of Spz, integrating signals sent by various
      secreted recognition molecules via more specialized SPs.

PMID- 16631590
TI  - Discrimination strategies of humans and rhesus monkeys for complex visual
      displays.
AB  - By learning to discriminate among visual stimuli, human observers can become
      experts at specific visual tasks. The same is true for Rhesus monkeys, the major
      animal model of human visual perception. Here, we systematically compare how
      humans and monkeys solve a simple visual task. We trained humans and monkeys to
      discriminate between the members of small natural-image sets. We employed the
      "Bubbles" procedure to determine the stimulus features used by the observers. On
      average, monkeys used image features drawn from a diagnostic region covering
      about 7% +/- 2% of the images. Humans were able to use image features drawn from
      a much larger diagnostic region covering on average 51% +/- 4% of the images.
      Similarly for the two species, however, about 2% of the image needed to be
      visible within the diagnostic region on any individual trial for correct
      performance. We characterize the low-level image properties of the diagnostic
      regions and discuss individual differences among the monkeys. Our results reveal
      that monkeys base their behavior on confined image patches and essentially ignore
      a large fraction of the visual input, whereas humans are able to gather visual
      information with greater flexibility from large image regions.

PMID- 16631591
TI  - The inversion effect in biological motion perception: evidence for a "life
      detector"?
AB  - If biological-motion point-light displays are presented upside down, adequate
      perception is strongly impaired. Reminiscent of the inversion effect in face
      recognition, it has been suggested that the inversion effect in biological motion
      is due to impaired configural processing in a highly trained expert system. Here,
      we present data that are incompatible with this view. We show that observers can
      readily retrieve information about direction from scrambled point-light displays
      of humans and animals. Even though all configural information is entirely
      disrupted, perception of these displays is still subject to a significant
      inversion effect. Inverting only parts of the display reveals that the
      information about direction, as well as the associated inversion effect, is
      entirely carried by the local motion of the feet. We interpret our findings in
      terms of a visual filter that is tuned to the characteristic motion of the limbs
      of an animal in locomotion and hypothesize that this mechanism serves as a
      general detection system for the presence of articulated terrestrial animals.

PMID- 16631592
TI  - Long-range directional movement of an interphase chromosome site.
AB  - Increasing evidence suggests functional compartmentalization of interphase
      nuclei. This includes preferential interior localization of gene-rich and early
      replicating chromosome regions versus peripheral localization of gene-poor and
      late replicating chromosome regions , association of some active genes with
      nuclear speckles or transcription "factories", and association of
      transcriptionally repressed genes with heterochromatic regions. Dynamic changes
      in chromosome compartmentalization imply mechanisms for long-range interphase
      chromatin movements. However, live cell imaging in mammalian cells has revealed
      limited chromatin mobility, described as "constrained diffusion". None of these
      studies, though, have examined a chromosome locus undergoing an inducible
      repositioning between two different nuclear compartments. Here we demonstrate
      migration of an interphase chromosome site from the nuclear periphery to the
      interior 1-2 hr after targeting a transcriptional activator to this site. Spot
      redistribution is perturbed by specific actin or nuclear myosin I mutants.
      Extended periods of chromosome immobility are interspersed with several minute
      periods in which chromosomes move unidirectionally along curvilinear paths
      oriented roughly perpendicular to the nuclear envelope at velocities of 0.1-0.9
      microm/min over distances of 1-5 microm. Our results suggest an active mechanism
      for fast and directed long-range interphase chromosome movements dependent
      directly or indirectly on actin/myosin.

PMID- 16631593
TI  - Understanding and managing HELLP syndrome: the integral role of aggressive
      glucocorticoids for mother and child.
AB  - Antepartum or postpartum HELLP syndrome constitutes an obstetric emergency that
      requires expert knowledge and management skills. The insidious and variable
      nature of disease presentation and progression challenges the clinician and
      complicates consensus on universally accepted diagnostic and classification
      criteria. A critical review of published research about this variant form of
      severe preeclampsia, focused primarily on what is known about the pathogenesis of
      this disorder as it relates to patient experience with corticosteroids for its
      management, leads to the conclusion that there is maternal-fetal benefit realized
      when potent glucocorticoids are aggressively used for its treatment. Although
      acknowledging the need for definitive multicenter trials to better define the
      limits of benefit and the presence of any maternal or fetal risk, and given an
      understanding of the nature of the disorder with its potential to cause
      considerable maternal morbidity and mortality, we recommend for the present that
      aggressively used potent glucocorticoids constitute the cornerstone of management
      for patients considered to have HELLP syndrome.

PMID- 16631594
TI  - Stimulation of cyclic AMP production by the Caenorhabditis elegans muscarinic
      acetylcholine receptor GAR-3 in Chinese hamster ovary cells.
AB  - Among the three G-protein-linked acetylcholine receptors (GARs) in Caenorhabditis
      elegans (C. elegans), GAR-3 is structurally and pharmacologically most similar to
      mammalian muscarinic acetylcholine receptors (mAChRs). Using Chinese hamster
      ovary (CHO) cells stably expressing GAR-3b, the major alternatively spliced
      isoform of GAR-3, we observed that carbachol stimulated cyclic AMP (cAMP)
      production in a dose- and time-dependent manner. The stimulating effect of
      carbachol was abolished by atropine, a muscarinic antagonist, indicating that the
      cAMP production is specifically mediated by GAR-3b. When the cells were treated
      with BAPTA-AM and EGTA, which reduce the cytosolic Ca(2+) level, carbachol
      stimulated cAMP accumulation was inhibited by approximately 56%. Inhibition of
      protein kinase C (PKC) by chronic treatment with phorbol 12-myristate 13-acetate
      (PMA) or by GF109203X decreased carbachol-stimulated cAMP production by as much
      as 68%. It thus appears that Ca(2+) and PKC are critically involved in GAR-3b
      mediated cAMP formation. We also observed that carbachol-stimulated cAMP
      production was further enhanced by pertussis toxin (PTX) treatment. This
      observation indicates that GAR-3b couples to a PTX-sensitive G protein,
      presumably Gi, to attenuate the cAMP accumulation. Taken together, our data show
      that GAR-3b stimulates cAMP production in CHO cells and suggest that GAR-3b
      couples to both stimulatory and inhibitory pathways to modulate the intracellular
      cAMP level.

PMID- 16631595
TI  - A self-assembled quantum dot probe for detecting beta-lactamase activity.
AB  - This communication describes a quantum dot probe that can be activated by a
      reporter enzyme, beta-lactamase. Our design is based on the principle of
      fluorescence resonance energy transfer (FRET). A biotinylated beta-lactamase
      substrate was labeled with a carbocyanine dye, Cy5, and immobilized on the
      surface of quantum dots through the binding of biotin to streptavidin pre-coated
      on the quantum dots. In assembling this nanoprobe, we have found that both the
      distance between substrates and the quantum dot surface, and the density of
      substrates are important for its function. The fluorescence emission from quantum
      dots can be efficiently quenched (up to 95%) by Cy5 due to FRET. Our final
      quantum dot probe, assembled with QD605 and 1:1 mixture of biotin and a Cy5
      labeled lactam, can be activated by 32microg/mL of beta-lactamase with 4-fold
      increase in the fluorescence emission.

PMID- 16631596
TI  - The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4
      silencing.
AB  - Somatic DNA methylation patterns are determined in part by the de novo
      methylation that occurs after early embryonic demethylation. Oct-3/4, a
      pluripotency gene, is unmethylated in the blastocyst, but undergoes de novo
      methylation and silencing during gastrulation. Here we show that the
      transcriptional repressor GCNF recruits DNA methyltransferase to the Oct-3/4
      promoter and facilitates its methylation. Although acetylation of histone H3 at
      lysine 9 (K9) and/or 14 (K14) and methylation of H3 at lysine 4 (K4) decrease
      during this period, as do Oct-3/4 transcript levels, H3K9 and H3K27 methylation
      levels remain constant, indicating that DNA methylation does not require
      repressive histone modifications. We found that GCNF interacts directly with
      Dnmt3 molecule(s) and verified that this interaction induces the methylation of
      the Oct-3/4 promoter. Our finding suggests a model in which differentiation
      induced GCNF recruits de novo DNA methyltransferase and facilitates the silencing
      of a pluripotency gene.

PMID- 16631597
TI  - cAMP differentially regulates gamma-globin gene expression in erythroleukemic
      cells and primary erythroblasts through c-Myb expression.
AB  - Our previous studies demonstrated roles of cyclic nucleotides in gamma-globin
      gene expression. We recently found that, upon activation of the cAMP pathway,
      expression of the gamma-globin gene is inhibited in K562 cells but induced in
      adult erythroblasts. Here we show that c-Myb, a proto-oncogene product that plays
      a role in cell growth and differentiation, is involved in the cAMP-mediated
      differential regulation of gamma-globin gene expression in K562 cells and primary
      erythroblasts. Our studies found that c-Myb is expressed at a high level in K562
      cells compared to primary erythroblasts, and that c-Myb expression is further
      increased following the treatment with forskolin, an adenylate cyclase activator.
      The induction of gamma-globin gene expression was also inhibited in K562 cells by
      raising the levels of c-Myb expression. Importantly, forskolin-induced erythroid
      differentiation in K562 cells, as determined by the expression of glycophorins
      and CD71, suggesting that high-level expression of c-Myb may not be sufficient to
      inhibit the differentiation of erythroid cells. In contrast, c-Myb was not
      expressed in adult erythroblasts treated with forskolin and primary erythroblasts
      may lack the c-Myb-mediated inhibitory mechanism for gamma-globin gene
      expression. Together, these results show that the cAMP pathway blocks gamma
      globin gene expression in K562 cells by increasing c-Myb expression and c-Myb
      plays a role in defining the mode of response of the gamma-globin gene to fetal
      hemoglobin inducers in erythroid cells.

PMID- 16631598
TI  - Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel.
AB  - Voltage-dependent Ca(2+) channels play important roles in cerebellar functions
      including motor coordination and learning. Since abundant expression of Ca(V)2.3
      Ca(2+) channel gene in the cerebellum was detected, we searched for possible
      deficits in the cerebellar functions in the Ca(V)2.3 mutant mice. Behavioral
      analysis detected in delayed motor learning in rotarod tests in mice heterozygous
      and homozygous for the Ca(V)2.3 gene disruption (Ca(V)2.3+/- and Ca(V)2.3-/-,
      respectively). Electrophysiological analysis of mutant mice revealed perplexing
      results: deficit in long-term depression (LTD) at the parallel fiber Purkinje
      cell synapse in Ca(V)2.3+/- mice but apparently normal LTD in Ca(V)2.3-/- mice.
      On the other hand, the number of spikes evoked by current injection in Purkinje
      cells under the current-clamp mode decreased in Ca(V)2.3 mutant mice in a gene
      dosage-dependent manner, suggesting that Ca(V)2.3 channel contributed to spike
      generation in Purkinje cells. Thus, Ca(V)2.3 channel seems to play some roles in
      cerebellar functions.

PMID- 16631599
TI  - Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of
      p56(Lck).
AB  - Lipoic acid is an antioxidant that suppresses and treats a model of multiple
      sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that
      treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in
      a concentration-dependent manner. LA treatment of Con A stimulated PBMC
      specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by
      LA was excluded by using monoclonal antibodies targeting different domains of
      CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting
      that endocytosis was involved in its downmodulation. LA is in a unique category
      of compounds that induce CD4 downmodulation by various mechanisms (e.g.,
      gangliosides). We hypothesized that LA might induce dissociation of p56(Lck) from
      CD4, thus leading to its downmodulation. Immunoblot analyses demonstrated reduced
      co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and
      precipitation of CD4. This unique immunomodulatory effect of LA warrants further
      investigation.

PMID- 16631600
TI  - Molecular and functional characterization of a spermidine transporter (TcPAT12)
      from Trypanosoma cruzi.
AB  - Trypanosoma cruzi, the etiological agent of Chagas' disease, is the only
      eukaryotic cell which lacks the ability to synthesize polyamines de novo. In this
      work, we describe for the first time the molecular and biochemical properties of
      a high-affinity spermidine transporter from T. cruzi. The transporter gene
      TcPAT12 was functionally expressed in Xenopus laevis oocytes, showing high levels
      of spermidine uptake. Similar apparent affinity constants for spermidine uptake
      were obtained when comparing T. cruzi epimastigotes and heterologous expressed
      TcPAT12 in X. laevis. In addition, TcPAT12 also transports putrescine and the
      amino acid l-arginine at lower rates than spermidine.

PMID- 16631601
TI  - Human Mpv17-like protein is localized in peroxisomes and regulates expression of
      antioxidant enzymes.
AB  - M-LP (Mpv17-like protein) is a protein that was initially identified in mouse
      tissues and shows high sequence homology with Mpv17 protein, a peroxisomal
      membrane protein involved in the development of early-onset glomerulosclerosis
      [R. Iida, T. Yasuda, E. Tsubota, H. Takatsuka, M. Masuyama, T. Matsuki, K. Kishi,
      M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising
      a transmembrane domain and a positively charged loop and up-regulates expression
      of the manganese superoxide dismutase gene, J. Biol. Chem. 278 (2003) 6301-6306].
      Here we report the identification and characterization of a human homolog of the
      M-LP (M-LPH) gene. The M-LPH gene is composed of four exons, extends over 14kb on
      chromosome 16p13.1, and is expressed as two alternatively spliced variants
      comprising four and three exons, respectively, which include open-reading frames
      encoding two distinct isoforms composed of 196 (M-LPH1) and 147 (M-LPH2) amino
      acids, respectively. These two variants were expressed ubiquitously in human
      tissues, however only M-LPH1 was detected at the protein level. Dual-color
      confocal analysis of COS-7 cells transfected with a green fluorescent protein
      tagged M-LPH1 demonstrated that M-LPH1 is localized in peroxisomes. In order to
      elucidate the function of M-LPH1, we examined the mRNA levels of several enzymes
      involved in the metabolism of reactive oxygen species in COS-7 cells and found
      that transfection with M-LPH1 down-regulates expression of the plasma glutathione
      peroxidase and catalase genes. These results show the existence of the human
      homolog of M-LP and its participation in reactive oxygen species metabolism.

PMID- 16631602
TI  - Immobilization of histidine-tagged proteins by magnetic nanoparticles
      encapsulated with nitrilotriacetic acid (NTA)-phospholipids micelle.
AB  - We described the development of functionalized magnetic nanoparticles (MNPs) with
      PEG-modification, a phospholipids micelle coating, and their use in manipulating
      histidine-tagged proteins. Highly monodisperse MNPs were synthesized in an
      organic solvent and could be phase-transferred into an aqueous solution by
      encapsulating the nanoparticles with a phospholipids micelle. The phospholipids
      micelle coating rendered the nanoparticles highly water-soluble, and the
      functional groups of the phospholipids coating allowed for the bioconjugation of
      various moieties, such as fluorescent molecules and engineered proteins.
      Functionalized phospholipids, such as nitrilotriacetic acid (NTA)-phospholipids,
      caused the MNPs to bind and allowed for manipulation of histidine-tagged
      proteins. Due to their high surface/volume ratio, the MNPs showed better
      performance (about 100 times higher) in immobilizing engineered proteins than
      conventional micrometer-sized beads. This demonstrates that MNPs coated with
      phospholipids micelle can be a versatile platform for the effective manipulation
      of various kinds of engineered proteins, which is very important in the field of
      proteomics. It is expected that a combination of MNPs with optical fluorescent
      molecules can find applications in bimodal (magnetic and optical) molecular
      imaging nanoprobes.

PMID- 16631603
TI  - Suppression of atherogenesis by delivery of TGFbeta1ACT using adeno-associated
      virus type 2 in LDLR knockout mice.
AB  - TGFbeta(1) deficiency has been attributed to the development of atherosclerosis.
      There is, however, little direct evidence for this concept. To examine this
      hypothesis, low-density lipoprotein receptor knockout (LDLR(-/-)) mice were
      injected via tail vein with recombinant adeno-associated virus type 2 (rAAV)
      carrying a bioactive TGFbeta(1) mutant (AAV/TGFbeta1ACT, n=10) or granulocyte
      macrophage-colony stimulating factor (AAV/GM-CSF, n=10, a negative control) or
      saline (n=9, control), and then put on a high cholesterol diet. At 18 weeks,
      blood lipids were found to be similarly elevated in all LDLR(-/-) mice.
      TGFbeta1ACT and GM-CSF (DNA, mRNA, and protein) were highly expressed in the
      tissues of mice given TGFbeta1ACT or AAV/GM-CSF, respectively, showing sustained
      transfection following gene delivery by the systemic route. Saline-treated and
      AAV/GM-CSF-treated LDLR(-/-) mice showed extensive areas of atherosclerotic
      lesion formation. There was evidence of intense oxidative stress (nitrotyrosine
      staining), inflammation (CD68 staining), and expression of adhesion molecules and
      the ox-LDL receptor LOX-1 (gene array analysis) in the atherosclerotic tissues.
      Importantly, atherosclerotic lesion formation was markedly inhibited in the LDLR(
      /-) mice given AAV/TGFbeta1ACT. Expression of adhesion molecules and LOX-1,
      oxidative stress, and inflammatory response all were inhibited in the mice given
      AAV/TGFbeta1ACT (P<0.05 vs. saline-treated or GM-CSF-treated LDLR(-/-) mice).
      These data for the first time demonstrate that systemic delivery of TGFbeta1ACT
      gene via AAV can inhibit formation of atherosclerotic lesions, possibly via anti
      inflammatory and anti-oxidant mechanisms. These findings suggest a novel view of
      TGFbeta(1) in atherogenesis and a potential new gene therapy for treatment of
      atherosclerosis.

PMID- 16631604
TI  - Methylation of the ATM promoter in glioma cells alters ionizing radiation
      sensitivity.
AB  - Glioblastomas are among the malignancies most resistant to radiation therapy. In
      contrast, cells lacking the ATM protein are highly sensitive to ionizing
      radiation. The relationship between ATM protein expression and radiosensitivity
      in 3 glioma cell lines was examined. T98G cells exhibited normal levels of ATM
      protein, whereas U118 and U87 cells had significantly lower levels of ATM and
      increased (>2-fold) sensitivity to ionizing radiation compared to T98G cells. The
      ATM promoter was methylated in U87 cells. Demethylation by azacytidine treatment
      increased ATM protein levels in the U87 cells and decreased their
      radiosensitivity. In contrast, the ATM promoter in U118 cells was not methylated.
      Further, expression of exogenous ATM did not significantly alter the
      radiosensitivity of U118 cells. ATM expression is therefore heterogeneous in the
      glioma cells examined. In conclusion, methylation of the ATM promoter may account
      for the variable radiosensitivity and heterogeneous ATM expression in a fraction
      of glioma cells.

PMID- 16631605
TI  - Age-associated cellular relocation of Sod 1 as a self-defense is a futile
      mechanism to prevent vascular aging.
AB  - Vascular aging is characterized by the presence of chronic oxidative stress.
      Although cytosolic Sod 1 has a key role in the detoxification of superoxide
      ((*)O(2)(-)), little is known about its importance in vascular aging. We found
      that inhibition of Sod 1 had no effect on (*)O2- generation. Furthermore, its
      expression decreased in an age-dependent manner. Interestingly, Sod 1 loses its
      membrane-association and is also lost from the caveolae with increasing age.
      Instead, a relocation of Sod 1 to the mitochondria takes place, presumably in an
      attempt to maintain mitochondrial integrity and to counter-balance age-associated
      oxidative stress. Unlike Sod 2, which is constitutively expressed in mitochondria
      to control (*)O2- radical fluxes, Sod 1 is not inactivated by peroxynitrite and
      is not nitrated as a function of age. These novel insights into oxidative stress
      associated vascular aging and the understanding about how redox-systems are
      regulated in old age may identify new targets to ameliorate aging as the greatest
      cardiovascular risk factor.

PMID- 16631606
TI  - Ebp1 is a dsRNA-binding protein associated with ribosomes that modulates
      eIF2alpha phosphorylation.
AB  - dsRNA-binding domains (dsRBDs) characterize an expanding family of proteins
      involved in different cellular processes, ranging from RNA editing and processing
      to translational control. Here we present evidence that Ebp1, a cell growth
      regulating protein that is part of ribonucleoprotein (RNP) complexes, contains a
      dsRBD and that this domain mediates its interaction with dsRNA. Deletion of
      Ebp1's dsRBD impairs its localization to the nucleolus and its ability to form
      RNP complexes. We show that in the cytoplasm, Ebp1 is associated with mature
      ribosomes and that it is able to inhibit the phosphorylation of serine 51 in the
      eukaryotic initiation factor 2 alpha (eIF2alpha). In response to various cellular
      stress, eIF2alpha is phosphorylated by distinct protein kinases (PKR, PERK, GCN2,
      and HRI), and this event results in protein translation shut-down. Ebp1
      overexpression in HeLa cells is able to protect eIF2alpha from phosphorylation at
      steady state and also in response to various treatments. We demonstrate that Ebp1
      interacts with and is phosphorylated by the PKR protein kinase. Our results
      demonstrate that Ebp1 is a new dsRNA-binding protein that acts as a cellular
      inhibitor of eIF2alpha phosphorylation suggesting that it could be involved in
      protein translation control.

PMID- 16631607
TI  - Modulation of functional properties of KCNQ1 channel by association of KCNE1 and
      KCNE2.
AB  - The KCNE proteins (KCNE1 through KCNE5) function as beta-subunits of several
      voltage-gated K(+) channels. Assembly of KCNQ1 K(+) channel alpha-subunits and
      KCNE1 underlies cardiac I(Ks), while KCNQ1 interacts with all other members of
      KCNE forming complexes with different properties. Here we investigated synergic
      actions of KCNE1 and KCNE2 on functional properties of KCNQ1 heterologously
      expressed in COS7 cells. Patch-clamp recordings from cells expressing KCNQ1 and
      KCNE1 exhibited the slowly activating current, while co-expression of KCNQ1 with
      KCNE2 produced a practically time-independent current. When KCNQ1 was co
      expressed with both of KCNE1 and KCNE2, the membrane current exhibited a voltage-
      and time-dependent current whose characteristics differed substantially from
      those of the KCNQ1/KCNE1 current. The KCNQ1/KCNE1/KCNE2 current had a more
      depolarized activation voltage, a faster deactivation kinetics, and a less
      sensitivity to activation by mefenamic acid. These results suggest that KCNE2 can
      functionally couple to KCNQ1 even in the presence of KCNE1.

PMID- 16631608
TI  - Universal initiator nucleotides for the enzymatic synthesis of 5'-amino- and 5'
      thiol-modified RNA.
AB  - We report the chemical synthesis of 5'-amino- and 5'-thiol-hexaethylene glycol
      guanosine nucleotides and their enzymatic incorporation into RNA, followed by
      chemical modifications at their nucleophilic ends. By using two similar routes,
      the conjugates of guanosine-5'-monophosphate and hexaethylene glycol with
      attached reactive groups (SH or NH(2)) were synthesized using phosphoramidite
      chemistry, and characterized by MALDI TOF mass spectrometry. These initiator
      molecules were efficiently incorporated into RNA at the 5'-end by run-off
      transcription using T7 RNA polymerase. The potential of these RNA conjugates for
      a broad reaction range with electrophiles is shown here, thereby enabling their
      use for diverse biochemical applications.

PMID- 16631609
TI  - Changes in S1P1 and S1P2 expression during embryonal development and primitive
      endoderm differentiation of F9 cells.
AB  - Sphingosine 1-phosphate (S1P) is a ligand for S1P family receptors (S1P(1)
      S1P(5)). Of these receptors, S1P(1), S1P(2), and S1P(3) are ubiquitously
      expressed in adult mice, while S1P(4) and S1P(5) are tissue specific. However,
      little is known of their expression during embryonal development. We performed
      Northern blot analyses in mouse embryonal tissue and found that such expression
      is developmentally regulated. We also examined the expression of these receptors
      during primitive endoderm (PrE) differentiation of mouse F9 embryonal carcinoma
      (EC) cells, a well-known in vitro endoderm differentiation system. S1P(2) mRNA
      was abundantly expressed in F9 EC cells, but little S1P(1) and no S1P(3), S1P(4),
      or S1P(5) mRNA was detectable. However, S1P(1) mRNA expression was induced during
      EC-to-PrE differentiation. Studies using small interference RNA of S1P(1)
      indicated that increased S1P(1) expression is required for PrE differentiation.
      Thus, S1P(1) may play an important function in PrE differentiation that is not
      substituted for by S1P(2).

PMID- 16631610
TI  - A testis-specific and testis developmentally regulated tumor protein D52 (TPD52)
      like protein TPD52L3/hD55 interacts with TPD52 family proteins.
AB  - Tumor protein D52-like proteins (TPD52) are small coiled-coil motif bearing
      proteins that were first identified in breast cancer. TPD52 and related proteins
      have been implicated in cell proliferation, apoptosis, and vesicle trafficking.
      To date, three human TPD52 members had been identified, named hD52 (TPD52), hD53
      (TPD52L1), and hD54 (TPD52L2). The most important characteristic of the protein
      family is a highly conserved coiled-coil motif that is required for homo- and
      heteromeric interaction with other TPD52-like proteins. Herein, we identified a
      novel TPD52-like sequence (TPD52L3, or hD55) in human testis using cDNA
      microarray. Sequence analysis of the deduced protein suggests that hD55 contains
      a coiled-coil motif and is highly conserved compared with other TPD52-like
      sequences. Yeast two-hybrid and GST pull-down assays revealed that hD55 interacts
      with hD52, hD53, hD54, and itself. cDNA microarray detection found that hD55 was
      expressed at 5.6-fold higher levels in adult testis than in fetal testis.
      Additionally, the expression profile shows that hD55 is testis-specific,
      indicating a potential role for hD55 in testis development and spermatogenesis.

PMID- 16631611
TI  - Signaling pathways involved in PDGF-evoked cellular responses in human RPE cells.
AB  - We examined whether PDGF may directly stimulate the expression of VEGF by retinal
      pigment epithelial (RPE) cells in vitro, and the involvement of three signal
      transduction pathways in the regulation of PDGF-evoked cell proliferation,
      migration, and production of VEGF-A was investigated. PDGF stimulated the gene
      and protein expression of VEGF-A by RPE cells, and increased cell proliferation
      and chemotaxis. PDGF activated all signaling pathways investigated, as determined
      by increased phosphorylation levels of ERK1/2, p38, and Akt proteins. The three
      signaling pathways were involved in the mediation of PDGF-evoked cell
      proliferation, while p38 and PI3K mediated cell migration, and PI3K mediated
      secretion of VEGF-A. In addition to VEGF-A, the cells expressed mRNAs for various
      members of the VEGF family and for their receptors, including VEGF-B, -C, -D, flt
      1, and KDR. The data indicate that PDGF selectively stimulates the expression of
      VEGF-A in RPE cells. PDGF evokes at least three signal transduction pathways
      which are differentially involved in various cellular responses.

PMID- 16631612
TI  - Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets.
AB  - Pyruvate dehydrogenase (PDH) converts pyruvate to acetyl-CoA, links glycolysis to
      the Krebs cycle, and plays an important role in glucose metabolism and insulin
      secretion in pancreatic beta cells. In beta cells from obese and Type 2 diabetic
      animals, PDH activity is significantly reduced. PDH is negatively regulated by
      multiple pyruvate dehydrogenase kinase (PDK) isotypes (PDK subtypes 1-4).
      However, we do not know whether fatty acids or high glucose modulate PDKs in
      islets. To test this we determined PDH and PDK activities and PDK gene and
      protein expression in C57BL/6 mouse islets. Both high palmitate and high glucose
      reduced active PDH activity and increased PDK activity. The gene and protein for
      PDK3 were not expressed in islets. Palmitate up-regulated mRNA expression of PDK1
      (2.9-fold), PDK2 (1.9-fold), and PDK4 (3.1-fold). High glucose increased PDK1
      (1.8-fold) and PDK2 (2.7-fold) mRNA expression but reduced PDK4 mRNA expression
      by 40 percent in cultured islets. Changed PDK expression was confirmed by Western
      blotting. These results demonstrate that in islet cells both fat and glucose
      regulate PDK gene and protein expression and indicate that hyperglycemia and
      hyperlipidemia contribute to the decline in diabetic islet PDH activity by
      increasing mRNA and protein expression of PDK.

PMID- 16631613
TI  - Localization of Rheb to the endomembrane is critical for its signaling function.
AB  - Rheb, a small GTPase, has emerged as a key molecular switch that directly
      regulates the activity of the mammalian target of rapamycin (mTOR). Similar to
      other members of the Ras superfamily, Rheb has a C-terminal CaaX box that is
      subject to farnesylation. This study reports that farnesylation is a key
      determinant of Rheb's subcellular localization and directs its association with
      the endomembrane. Timed imaging of live cells expressing EGFP-Rheb reveals that
      following brief association with the ER, Rheb localizes to highly ordered,
      distinct structures within the cytoplasm that display characteristics of Golgi
      membranes. Failure of Rheb to localize to the endomembrane impairs its ability to
      interact with mTOR and activate downstream targets. Consistent with the notion
      that the endomembrane may serve as a platform for the assembly of a functional
      Rheb/mTOR complex, treatment of cells with brefeldin A interferes with
      transmission of Rheb signals to p70S6K.

PMID- 16631614
TI  - Molecular cloning and characterization of human Castor, a novel human gene
      upregulated during cell differentiation.
AB  - Castor is a zinc finger transcription factor that controls cell fate within
      neuroblast cell lineages in Drosophila melanogaster. Here, we describe the
      cloning and characterization of a human castor gene (CASZ1) that is structurally
      homologous to Drosophila castor. We find the expression of castor gene is
      increased when cells of neural origin as well as mesenchymal origin are induced
      to differentiation. CASZ1 is expressed in a number of normal tissues and exists
      in at least two mRNA species of 4.4 and 8.0kb. They are named hCasz5 and hCasz11
      because the predicted proteins have 5 and 11 zinc fingers, respectively. Deletion
      analysis of the proximal 5'-flanking sequences delineates sequences sufficient to
      drive transcription in cells of neural and non-neural origin. Both hCasz5 and
      hCasz11 localize predominantly in the nucleus, consistent with their role as Zn
      finger containing transcription factor. CASZ1 is expressed in a number of human
      tumors and localizes to a chromosomal region frequently lost in tumors of
      neuroectodermal origin.

PMID- 16631615
TI  - 1-Cinnamoyl-3,11-dihydroxymeliacarpin is a natural bioactive compound with
      antiviral and nuclear factor-kappaB modulating properties.
AB  - We have reported the isolation of the tetranortriterpenoid 1-cinnamoyl-3,11
      dihydroxymeliacarpin (CDM) from partially purified leaf extracts of Melia
      azedarach L. (MA) that reduced both, vesicular stomatitis virus (VSV) and Herpes
      simplex virus type 1 (HSV-1) multiplication. CDM blocks VSV entry and the
      intracellular transport of VSV-G protein, confining it to the Golgi apparatus, by
      pre- or post-treatment, respectively. Here, we report that HSV-1 glycoproteins
      were also confined to the Golgi apparatus independently of the nature of the host
      cell. Considering that MA could be acting as an immunomodulator preventing the
      development of herpetic stromal keratitis in mice, we also examined an eventual
      effect of CDM on NF-kappaB signaling pathway. CDM is able to impede NF-kappaB
      activation in HSV-1-infected conjunctival cells and leads to the accumulation of
      p65 NF-kappaB subunit in the cytoplasm of uninfected treated Vero cells. In
      conclusion, CDM is a pleiotropic agent that not only inhibits the multiplication
      of DNA and RNA viruses by the same mechanism of action but also modulates the NF
      kappaB signaling pathway.

PMID- 16631616
TI  - Post-treatment with the Ca(2+)-Mg(2+)-endonuclease inhibitor aurintricarboxylic
      acid prevents peroxynitrite-induced DNA damage and death of murine astrocytes.
AB  - Oxidative stress plays critical roles in aging, cell death, and many diseases.
      Peroxynitrite is one of the major reactive oxygen species which mediates cell
      injury in a number of illnesses. It is of importance to identify the downstream
      events in peroxynitrite-initiated cell death cascade for preventing peroxynitrite
      toxicity. Ca(2+)-Mg(2+)-endonucleases have been suggested as the endonucleases
      that execute DNA fragmentation in several apoptotic cascades. In this study, we
      determined if astrocytes and neurons express the genes of Ca(2+)-Mg(2+)
      endonucleases. We also tested our hypothesis that post-treatment with the Ca(2+)
      Mg(2+)-endonuclease inhibitor aurintricarboxylic acid can decrease peroxynitrite
      induced DNA damage and death of astrocytes. We found that both astrocytes and
      neurons express DNase I-like endonuclease-a major isoform of Ca(2+)-Mg(2+)
      endonucleases. Treatment of astrocytes with aurintricarboxylic acid either before
      or after peroxynitrite exposures can profoundly decrease peroxynitrite-induced
      DNA damage and cell death. These results suggest that Ca(2+)-Mg(2+)-endonucleases
      may be a key downstream component in peroxynitrite-initiated cell death cascade
      in astrocytes and some other cell types, and aurintricarboxylic acid could be
      used to decrease peroxynitrite-induced DNA damage at delayed phases.

PMID- 16631617
TI  - Cautions in the use of biomarkers of oxidative damage; the vascular and
      antioxidant effects of dark soy sauce in humans.
AB  - Dark soy sauce (DSS) is a powerful antioxidant in vitro. We investigated whether
      this effect could occur in vivo and improve vascular function. Healthy human
      subjects were given DSS or placebo meals in a randomized, crossover study. Blood
      and urine were sampled before and 1, 2, 3, and 4h after the meal for F(2)
      isoprostanes (total, free, and esterified) and 8OHdG measurements. Blood
      pressure, vascular augmentation index (AIx), and heart rate (HR) were also
      measured. Plasma total F(2)-isoprostanes significantly decreased 3h after placebo
      and the decrease was greater for DSS. Plasma free and esterified F(2)
      isoprostanes were also significantly decreased after DSS. Both placebo and DSS
      meals increased urinary F(2)-isoprostanes at 1h but not thereafter, and lowered
      urinary 8OHdG levels, DBP and AIx, and increased HR. We conclude that DSS
      decreases lipid peroxidation in vivo. However, oxidative damage biomarkers
      changed after the placebo meal, a phenomenon to consider when designing
      interventional studies.

PMID- 16631618
TI  - Autocrine activation of cultured macrophages by brain-derived neurotrophic
      factor.
AB  - To elucidate a significance of the expression of brain-derived neurotrophic
      factor (BDNF) in the activated microglia/macrophages of the injured central
      nervous system, we examined BDNF actions on or BDNF synthesis by macrophages
      cultured from the mouse peritoneal cavity. They synthesized BDNF and neurotrophin
      3 (NT-3) in addition to expressing high-affinity neurotrophin receptors, full
      length TrkB (FL), truncated TrkB (TK(-)), and TrkC, thus suggesting an autocrine
      influence of BDNF and NT-3. BDNF, but not NT-3, enhanced phagocytic activity and
      stimulated synthesis/secretion of interleukin-1beta in the same manner as
      lipopolysaccharide (LPS). Furthermore, there was a significant correlation of the
      phagocytic activity with the expression of BDNF or TrkB (FL). These results imply
      that the phagocytic activity of macrophages depends on BDNF synthesis and/or TrkB
      (FL) expression, suggesting that BDNF participates in the activation processes of
      macrophages by acting in an autocrine manner.

PMID- 16631619
TI  - Expression and transport characterisation of the wheat low-affinity cation
      transporter (LCT1) in the methylotrophic yeast Pichia pastoris.
AB  - The low-affinity cation transporter (LCT1) from wheat (Triticum aestivum) was
      expressed in the methylotrophic yeast Pichia pastoris and its transport
      characteristics studied employing Ca(45) and Cd(109). A clone (LCT1#3) with the
      highest uptake of 14pmol of Ca/10(6)cells/10min when exposed to 100microM Ca(45)
      was chosen for further Ca(45) and Cd(109) transport characteristics. We report
      for the first time a K(m) for Ca by LCT1 of 0.43+/-0.15mM Ca activity which
      confirms LCT1 to be a low affinity transporter. Interestingly, the expression of
      LCT1 in Pichia resulted in reduced Cd(109) uptake compared to wild type cells,
      when cells were exposed to >or=60microM Cd. This is the first report of the
      ability of a heterologously expressed transporter to reduce the activity of
      endogenous transporter proteins to transport Cd. To our knowledge, this is the
      first demonstration of functional expression of a plant ion transporter using P.
      pastoris.

PMID- 16631620
TI  - Cardioprotective effects of recombinant human erythropoietin in rats with
      experimental autoimmune myocarditis.
AB  - Erythropoietin (EPO) has been known to have cytoprotective effects on several
      types of tissues, presumably through modulation of apoptosis and inflammation.
      The effect of EPO on myocardial inflammation, however, has not yet been
      clarified. We investigated the cardioprotective effects of EPO in rats with
      experimental autoimmune myocarditis (EAM). Seven-week-old Lewis rats immunized
      with cardiac myosin were treated either with EPO or vehicle and were examined on
      day 22. EPO attenuated the functional and histological severity of EAM along with
      suppression of mRNAs of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6
      in the hearts as well as a reduction of apoptotic cardiomyocytes. The EPO
      receptor (EPO-R) was upregulated in the myocardium of EAM compared with that of
      healthy rats. These results may suggest that EPO ameliorated the progression of
      EAM by modulating myocardial inflammation and apoptosis.

PMID- 16631621
TI  - Pbx1 and Meis1 regulate activity of the Xenopus laevis Zic3 promoter through a
      highly conserved region.
AB  - Xenopus Zic3 (zinc finger in the cerebellum-3) is expressed in the dorsal neural
      tube of tailbud embryos and tadpoles. We have isolated a 3.1kb DNA fragment from
      the Xenopus laevis Zic3 locus that drives proper expression of a GFP reporter in
      transgenic frog tailbud embryos and tadpoles. This fragment contains regions that
      are highly similar among frogs, mice, and humans. One extremely conserved region
      contains a predicted Pbx binding site. We found that the transcription factors
      Pbx1b and Meis1 can bind this site and synergistically transactivate expression
      of a reporter containing the conserved region. Finally, we found that an intact
      Pbx site is essential for normal Zic3 promoter activity in transgenic frog
      embryos. Our data strongly suggest that a highly conserved region of the Zic3
      promoter functions by direct interaction with Pbx1b and Meis1.

PMID- 16631622
TI  - Internal initiation of mRNA translation in insect cell mediated by an internal
      ribosome entry site (IRES) from shrimp white spot syndrome virus (WSSV).
AB  - Internal initiation of mRNA translation can be mediated by internal ribosome
      entry site (IRES) elements which are located mainly in RNA viruses as well as
      certain mammalian and insect mRNA molecules. Thus far, only one DNA virus has
      been discovered to contain IRES element. In this investigation, an IRES element
      from white spot syndrome virus (WSSV), a DNA virus of marine shrimp, was
      demonstrated to direct the efficient translation of dicistronic mRNA in
      Trichoplusia ni insect cells. The IRES was inserted between glutathione S
      transferase (GST) and green fluorescent protein (GFP) genes to construct a
      dicistronic cassette (GST-IRES-GFP). After transfection of this dicistronic
      cassette in insect cell, the Northern blot indicated that only one transcript
      corresponding to the mRNA of GST-IRES-GFP could be detected. However, the GST and
      GFP genes were simultaneously translated as revealed by Western blot and
      fluorescent microscopy, respectively. Based on sequence orientation and deletion
      analyses, the IRES element was 180 nucleotides (nt) in length and orientation
      dependent. By comparison with that of cap-dependent initiation, the translation
      efficiency mediated by IRES was 98.77%. This finding promises that the WSSV IRES
      could be very useful to co-express two or more proteins due to its shorter length
      and higher translation efficiency.

PMID- 16631623
TI  - nSMase2 activation and trafficking are modulated by oxidative stress to induce
      apoptosis.
AB  - We have previously shown that accumulation of ceramide, triggered by hydrogen
      peroxide (H(2)O(2)), induces apoptosis of human airway epithelial (HAE) cells.
      Under oxidant exposure, a lung sphingomyelinase (SMase) is activated and displays
      continued ceramide generation and pro-apoptotic signaling, thus leading to the
      pathological apoptosis that causes lung injury. In a search for a specific SMase
      that is modulated by oxidative stress, we recently cloned nSMase2 from monkey
      lung tissue and HAE cells. Here, we show that this nSMase2 is up-regulated by an
      oxidant (H(2)O(2)) and is inhibited by an antioxidant (glutathione (GSH)).
      Moreover, nSMase2 subcellular localization is governed by oxidant exposure, which
      leads to its preferential trafficking to the plasma membrane, where it generates
      ceramide and induces apoptosis. On the other hand, exposure to GSH results in
      nSMase2 trafficking to the nucleus, where it neither generates ceramide nor
      induces apoptosis.

PMID- 16631624
TI  - Calibration of acoustic transients.
AB  - This article reviews the appropriate stimulus parameters (click duration,
      toneburst envelope) that should be used when eliciting auditory brainstem
      responses from mice. Equipment specifications required to calibrate these
      acoustic transients are discussed. Several methods of calibrating the level of
      acoustic transients are presented, including the measurement of peak equivalent
      sound pressure level (peSPL) and peak sound pressure level (pSPL). It is hoped
      that those who collect auditory brainstem response thresholds in mice will begin
      to use standardized methods of acoustic calibration, so that hearing thresholds
      across mouse strains obtained in different laboratories can more readily be
      compared.

PMID- 16631625
TI  - In vitro responsiveness of human-drug-resistant tissue to antiepileptic drugs:
      insights into the mechanisms of pharmacoresistance.
AB  - Pharmacoresistance in epileptic patients may be ascribed to at least two, not
      mutually exclusive, mechanisms: a pharmacokinetic mechanism and a decreased
      sensitivity or availability of targets to antiepileptic drugs (AEDs; i.e.,
      carbamazepine and phenytoin (CBZ, PHT)). Brain:plasma drug concentration ratios
      were determined intraoperatively during lobectomies performed to alleviate drug
      resistant seizures. The brain:plasma ratio of CBZ was 1.48 when therapeutic serum
      levels (15-34 microM) were achieved. When concentrations of CBZ found in multiple
      drug-resistant brain were directly applied to human cortical slices from drug
      resistant patients made hyperexcitable and hypersynchronous by Mg(2+)-free media,
      bursting frequency was not significantly affected and overall excitability was
      reduced by 40%. Similar results were obtained for PHT. At higher AED
      concentrations (60-200 microM), a dose-dependent decrease of bursting frequency
      and amplitude was observed. Slices from drug-resistant epileptic patients made
      hypersynchronous/hyperexcitable by elevated potassium or inhibition of GABA-A
      receptors behaved similarly. Of note is the response of slices from human
      multiple-drug-resistant brain, which was greater than in rodent cortex from naive
      animals. Taken together, our results support the hypothesis that multiple drug
      resistance to AEDs involves cerebrovascular changes that impede the achievement
      of appropriate drug levels in the central nervous system.

PMID- 16631626
TI  - Inhibition of basic leucine zipper transcription is a major mediator of atrial
      dilatation.
AB  - OBJECTIVE: Atrial fibrillation is the most prevalent clinically significant
      cardiac arrhythmia. Atrial dilatation, a predictor of atrial fibrillation, is
      thought to result from increased ventricular pressure. However, the underlying
      molecular mechanisms responsible for atrial dilatation are largely unknown. Here
      we sought to examine whether the expression of a basic leucine zipper inhibitor
      protein, JDP2, in the heart is sufficient for the generation of atrial
      dilatation. METHODS: A tetracycline-regulated transgene was used to express JDP2
      specifically in the mouse heart. Mice hearts were dissected and subjected to
      Northern and Western analysis, or analyzed by ECG recording and echocardiography.
      Regulation of gene expression was studied using electromobility shift assays and
      luciferase gene reporter analysis. RESULTS: Expression of JDP2 resulted in
      massive bi-atrial dilatation, defects in conduction, and a lethal phenotype.
      These effects were developmentally independent, acquired during adulthood, and
      were reversible upon abolishing of JDP2 expression. Connexin 40 and myosin light
      chain 2a expression were identified as potential target genes. CONCLUSION:
      Expression of basic leucine zipper transcription inhibitors is sufficient to
      results in atrial dilatation. This dilatation is acquired postnatally and is
      reversible. Thus, basic leucine zipper transcription inhibitors may be a relevant
      therapeutic target for preventing atrial dilatation and atrial fibrillation.

PMID- 16631627
TI  - Doxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in
      cardiomyocytes en route to apoptosis.
AB  - OBJECTIVE: The alpha 1-adrenoreceptor blocker doxazosin, which in the ALLHAT
      trial was associated with a greater risk of heart failure than the diuretic
      chlorthalidone, induces the apoptosis of human and murine cardiomyocytes
      regardless of alpha 1-adrenoreceptor blockade. We aimed to throw light on the
      mechanism of this process. METHODS: Murine cardiomyocytes (HL-1) and primary
      cultures of human and neonatal rat cardiomyocytes were treated with 25 micromol/L
      doxazosin for between 0.5 and 48 h. cDNA microarray analysis, real-time RT-PCR,
      and Western blotting were performed to detect possible changes in gene expression
      and/or activation of proteins that could be involved in doxazosin-induced
      apoptosis. RESULTS: Microarray analysis revealed changes in the expression of
      genes directly involved in the apoptotic end-stage of the cellular response to
      endoplasmic reticulum (ER) stress. Doxazosin considerably increased transcription
      and translation of gadd153, C/epb beta, and DOC-1 in cardiomyocytes as well as
      translocation of GADD153 to the nucleus, phosphorylation of p38 MAPK (a GADD153
      activator), and the initial phosphorylation and subsequent cleavage of focal
      adhesion kinase (FAK). Experiments repeated following blockade of alpha(1)
      adrenoreceptors showed no alteration of the above effects of doxazosin.
      CONCLUSION: Doxazosin induces the apoptosis of cardiomyocytes via the ER pathway,
      with increased production of C/EBP beta, GADD153 and DOC-1. Likewise it increases
      phosphorylation of the GADD153 activator p38 MAPK and induces first the
      phosphorylation, and then the cleavage, of FAK. These effects are not mediated by
      alpha 1-adrenoreceptors.

PMID- 16631628
TI  - Functional beta-adrenergic receptor signalling on nuclear membranes in adult rat
      and mouse ventricular cardiomyocytes.
AB  - OBJECTIVE: We sought to determine if different beta-adrenergic receptor (betaAR)
      subtypes, and their associated signalling machinery, are functionally localized
      to nuclear membranes. METHODS: Employing enriched nuclear preparations, we
      assayed the specific presence of betaAR by measuring 125I-cyanopindolol (CYP)
      binding, Western blotting, confocal microscopy and functional assays. RESULTS:
      Western blots of rat heart nuclear fractions and confocal immunofluorescent
      analysis of adult rat and mouse ventricular cardiomyocytes displayed the presence
      of beta 1AR and beta 3AR but, surprisingly, not the beta 2AR on nuclear
      membranes. Nuclear localization of downstream signalling partners Gs, Gi and
      adenylyl cyclases II and V/VI was also demonstrated. The functional relevance of
      nuclear betaAR was shown by receptor-mediated stimulation of adenylyl cyclase
      activity by isoproterenol but not the beta 3AR-selective agonist CL 316243 in
      enriched nuclear preparations. We also examined the effect of subtype-selective
      ligands on the initiation of RNA synthesis in isolated nuclei. Both isoproterenol
      and another beta 3AR-selective agonist, BRL 37344, increased RNA synthesis which
      was inhibited by pertussis toxin (PTX). Neither a beta 1AR-selective agonist,
      xamoterol, nor a beta 2AR-selective agonist, procaterol, was able to stimulate
      transcription. However, both CGP 20712A and ICI 118,551 blocked isoproterenol
      mediated effects to varying extents. PTX treatment also revealed that nuclear
      betaAR may be coupled to other signalling pathways in addition to Gi, as
      stimulation under these conditions reduced initiation of transcription below
      basal levels. CONCLUSION: These results highlight differential subcellular
      localization for betaAR subtypes and indicate that betaAR may have specific roles
      in regulating nuclear function in cardiomyocytes.

PMID- 16631629
TI  - Classical pathway complement activity in Familial Mediterranean fever.
AB  - OBJECTIVES: The present study emphasizes the important role of the immune
      reactions in the pathogenesis of Familial Mediterranean fever. In the present
      study, the total hemolytic activity of the complement and the activities of
      individual complement components, C1, C2, C3, and C4, were determined in the
      blood serum of 32 patients with FMF and 28 healthy subjects. DESIGN AND METHODS:
      Hemolytic assay was applied, measuring THAC and individual complement components'
      activities. The patients were divided into 3 groups upon the regularity of
      colchicine therapy: patients receiving regular, irregular and not receiving
      colchicine treatment for at least 1 year. RESULTS: No significant changes in the
      hemolytic activities of the C1, C2, C3, and C4 complement components were found
      between the healthy subjects and those FMF patients, who were receiving regular
      colchicine treatment. CONCLUSIONS: Our data obtained have raised a number of
      important questions relevant to FMF pathogenesis and once again confirms the
      efficiency of regular colchicine treatment.

PMID- 16631630
TI  - Coronary sinus orifice atresia with left superior vena cava in patients with
      univentricular heart.
AB  - Two patients with hypoplastic left heart syndrome had coronary sinus orifice
      atresia with persistent left superior vena cava. Both patients underwent
      successfully coronary sinus unroofing. One underwent surgery at the time of the
      bidirectional Glenn procedure and the other before creation of a total
      cavopulmonary connection. According to our population-based database, 10.3% of
      patients with univentricular heart have persistent left superior vena cava, and
      2.3% have associated coronary sinus orifice atresia. Our cases highlight the
      importance of recognizing this anomaly in patients with univentricular heart to
      avoid high coronary venous pressure, which is potentially lethal.

PMID- 16631631
TI  - Aortopulmonary fistula occurring 4 years after replacement of the ascending
      aorta.
AB  - A 62-year-old man presenting with congestive heart failure due to a fistula
      between an aortic pseudoaneurysm and the right pulmonary artery is described. The
      shunt occurred 4 years after aortic valve and supracoronary graft replacement and
      was diagnosed by transesophageal contrast echocardiography. After redo surgery
      the patient made an uneventful recovery.

PMID- 16631632
TI  - Rapid ventricular pacing to lower blood pressure during endograft deployment in
      the thoracic aorta.
AB  - Controlled hypotension is critical to the accurate deployment of aortic
      endografts and safe balloon post-dilation. We describe the use of rapid
      ventricular pacing during 15 aortic stenting procedures. An immediate and
      sustained reduction in both phasic and mean blood pressure was achieved in all
      patients. This procedure has advantages over pharmacologic or other methods of
      blood pressure reduction.

PMID- 16631633
TI  - How many lives did you save today?

PMID- 16631634
TI  - Defining operative mortality: it should be easy, but is it?

PMID- 16631635
TI  - The elephant trunk technique for staged repair of complex aneurysms of the entire
      thoracic aorta.
AB  - BACKGROUND: Extensive thoracic aortic aneurysms that involve the ascending, arch,
      and descending segments require challenging repairs associated with substantial
      morbidity and mortality. The purpose of this report is to evaluate contemporary
      outcomes after surgical repair of extensive thoracic aortic aneurysms using a two
      stage approach with the elephant trunk technique. METHODS: During a 15 1/2-year
      period, 148 consecutive patients underwent total aortic arch replacement using
      the elephant trunk technique. Seventy-six of these patients (51%, 76/148)
      returned for second-stage repair of the descending thoracic or thoracoabdominal
      aorta 4.9 +/- 7.5 months after the first stage. RESULTS: Operative mortality
      after the proximal aortic stage was 12% (18/148). Seven patients (5%) had
      strokes. Among the patients who subsequently underwent distal aortic repair,
      operative mortality was 4% (3/76). Two patients (3%) developed paraplegia. Long
      term survival after completing the second stage of repair was 70 +/- 6% at 5
      years and 59 +/- 7% at 8 years. CONCLUSIONS: Contemporary management of extensive
      thoracic aortic aneurysms using the two-stage elephant trunk technique yields
      acceptable short-term and long-term outcomes. This technique remains an important
      component of the surgical armamentarium.

PMID- 16631636
TI  - Midterm outcome in 158 consecutive Gore TAG thoracic endoprostheses: single
      center experience.
AB  - BACKGROUND: Despite recent improvements in surgical technique, some patients with
      descending thoracic aortic pathologies are unable to undergo open surgical repair
      due to significant comorbidities and/or unfavorable thoracic aortic anatomy. Some
      of these patients might be able to tolerate a less invasive approach, such as
      endoluminal grafting. We reviewed our consecutive clinical experience with the
      Gore TAG endoprosthesis (W. L. Gore & Assoc, Flagstaff, AZ) for the endovascular
      exclusion of assorted descending thoracic aortic pathologies in higher surgical
      risk patients. METHODS: After obtaining institutional review board approval, 158
      high surgical risk patients underwent attempted delivery of a Gore TAG thoracic
      endoprosthesis between February 2000 and July 2004. Indications for study
      enrollment were atherosclerotic aneurysm (n = 76), aortic dissection (n = 36),
      penetrating aortic ulcer (n = 15), contained rupture (n = 11), pseudoaneurysm (n
      = 10), traumatic aortic injury (n = 5), aortobronchial fistula (n = 4), and
      aortic coarctation (n = 1). RESULTS: The device was successfully delivered in 156
      (98.7%) patients. Mean patient age was 72 +/- 12.1 years. Three (1.9%) patients
      developed transient paraparesis after graft deployment and 1 (0.6%) patient
      developed paraplegia. While postimplantation endoleaks were observed in 18
      (11.5%) patients, only 12 patients required reintervention. Thirty-day mortality
      was 3.8% (6 of 156). Mean follow-up was 21.5 +/- 18.8 months, and the overall
      mortality was 17.3% (27 of 156). CONCLUSIONS: Endoluminal grafting of multiple
      types of descending thoracic aorta pathologies with the Gore TAG thoracic
      endoprosthesis is feasible and safe in higher surgical risk patients. Additional
      studies and long-term follow-up of these patients are warranted.

PMID- 16631637
TI  - Homograft implantation techniques in the aortic position: to preserve or replace
      the aortic root?
AB  - BACKGROUND: One determinant of durability of the homograft in the aortic position
      is the implantation technique. This study uses meta-analytical techniques to
      evaluate the differences in early and long-term outcomes of patients undergoing
      aortic homograft implantation with either a root replacement or a root preserving
      technique. METHODS: A systematic review of the literature (1965-2005) reporting
      results after homograft implantation in the aortic position with emphasis in the
      implantation technique was performed. Random and fixed-effects models were used.
      Cumulative and influential meta-analysis, graphic exploration, and sensitivity
      analysis were carried out to explain the heterogeneity between studies and to
      investigate potential publication bias. RESULTS: Eleven studies were included.
      None of the studies was randomized. There was no significant difference in early
      mortality between root replacement and root preserving groups (odds ratio = 2.57
      with 95% confidence interval [CI] 0.68-9.72 in random-effects model) and the root
      replacement group had a significantly lower rate of reoperation during long-term
      follow-up (hazard ratio = 0.55 with 95% CI 0.38-0.80 in random-effects model).
      Subgroup analysis focusing on patients having the subcoronary technique for
      homograft implantation showed similar results. Significant heterogeneity between
      studies can be detected. No publication bias was found. CONCLUSIONS: There was no
      significant difference in early mortality between root replacement and root
      preserving groups. However, the root replacement technique group had a
      significantly lower rate of reoperation during long-term follow-up. Excluding
      outliers identified in a funnel plot reduced the heterogeneity and reached a
      similar conclusion.

PMID- 16631638
TI  - Invited commentary.

PMID- 16631639
TI  - Clinical analysis of acute type A intramural hematoma: comparison between two
      different pathophysiological types.
AB  - BACKGROUND: Type A intramural hematoma (IMH) has two different etiologies, which
      are rupture of vasa vasorum and penetrating atherosclerotic ulcer (PAU); however,
      it is difficult to know which is the initiating event. METHODS: Between January
      1993 and August 2004, 28 patients of acute type A IMH were treated in our
      department and were divided into two groups, 20 patients with IMH probably caused
      by rupture of vasa vasorum (non-PAU group) and 8 patients with IMH probably
      caused by PAU (PAU group), according to pathologic specimen and atherosclerotic
      findings on computed tomography. Background factors, radiographic findings, and
      prognosis were analyzed retrospectively. RESULTS: Surgery was performed in 15
      patients (75%) in non-PAU group and 4 patients (50%) in PAU group during the
      first admission. Late progression was noted in 3 patients, and operation was
      required. Finally, operation was performed in 22 patients (78.6%). The history of
      myocardial infarction (p = 0.026) and chronic renal failure (p = 0.026) were more
      associated with PAU group than with non-PAU group. Ascending aortic diameter at
      the onset was significantly larger in non-PAU group (50.3 +/- 6.6 mm) than in PAU
      group (43.9 +/- 9.0 mm; p = 0.046), and there were significantly more ulcer
      lesions in PAU group (1.9 +/- 0.4) than in non-PAU group (1.1 +/- 0.4; p =
      0.0004). There was no significant difference in long-term survival rates between
      them. CONCLUSIONS: The PAU group patients have more coexisting atherosclerotic
      diseases and multiple aortic ulcer lesions with significantly mild ascending
      aortic dilatation compared with non-PAU group patients.

PMID- 16631640
TI  - Noninvasive assessment of brain injury in a canine model of hypothermic
      circulatory arrest using magnetic resonance spectroscopy.
AB  - BACKGROUND: Studies have confirmed the neuroprotective effect of diazoxide in
      canines undergoing hypothermic circulatory arrest (HCA). A decreased N-acetyl
      asparate:choline (NAA:Cho) ratio is believed to reflect the severity of
      neurologic injury. We demonstrated that noninvasive measurement of NAA:Cho with
      magnetic resonance spectroscopy facilitates assessment of neuronal injury after
      HCA and allows for evaluation of neuroprotective strategies. METHODS: Canines
      underwent 2 hours of HCA at 18 degrees C and were observed for 24 hours. Animals
      were divided into three groups (n = 15 in each group): normal (unoperated), HCA
      (HCA only), and HCA+diazoxide (pharmacologic treatment before HCA). The NAA:Cho
      ratios were obtained 24 hours after HCA by spectroscopy. Brains were immediately
      harvested for fresh tissue NAA quantification by mass spectrometry. Separate
      cohorts of HCA (n = 16) and HCA+diazoxide (n = 23) animals were kept alive for 72
      hours for daily neurologic assessment. RESULTS: Cortical NAA:Cho ratios were
      significantly decreased in HCA versus normal animals (1.01 +/- 0.29 versus 1.31
      +/- 0.23; p = 0.004), consistent with severe neurologic injury. Diazoxide
      pretreatment limited neurologic injury versus HCA alone, reflected in a preserved
      NAA:Cho ratio (1.21 +/- 0.27 versus 1.01 +/- 0.29; p = 0.05). Data were
      substantiated with fresh tissue NAA extraction. A significant decrease in
      cortical NAA was observed in HCA versus normal (7.07 +/- 1.9 versus 8.54 +/- 2.1
      micromol/g; p = 0.05), with maintenance of normal NAA levels after diazoxide
      pretreatment (9.49 +/- 1.1 versus 7.07 +/- 1.9 micromol/g; p = 0.0002). Clinical
      neurologic scores were significantly improved in the HCA+diazoxide group versus
      HCA at all time points. CONCLUSIONS: Neurologic injury remains a significant
      complication of cardiac surgery and is most severe after HCA. Magnetic resonance
      spectroscopy assessment of NAA:Cho ratios offers an early, noninvasive means of
      potentially evaluating neurologic injury and the effect of neuroprotective
      agents.

PMID- 16631641
TI  - Minimally invasive versus standard approach aortic valve replacement: a study in
      506 patients.
AB  - BACKGROUND: Minimally invasive aortic valve replacement through partial upper
      sternotomy has been shown to reduce surgical trauma, and, supposedly, decrease
      postoperative pain, blood loss, and hospital stay. METHODS: From October 1997
      until November 2004, 506 patients received isolated aortic valve replacement, of
      which 232 underwent the minimal access J-sternotomy approach (group 1). The
      control group (group 2) consisted of 274 patients who underwent aortic valve
      replacements by median sternotomy. We retrospectively reviewed outcomes of the
      patients in the early follow-up period. RESULTS: In group 1 and group 2,
      respectively, early mortality was 2.6% (6 patients) and 4.4% (12 patients). The
      minimal access group had reduced aortic cross-clamp and cardiopulmonary bypass
      times compared with conventional group: 61.8 +/- 16.6 versus 69.5 +/- 16.6
      minutes (p < 0.05) and 88.8 +/- 23.2 versus 100.2 +/- 22.6 minutes (p < 0.05),
      respectively. Mean blood loss was lower in group 1 compared with group 2 (p <
      0.05). Intensive care unit and hospital stays were shorter in the minimal access
      group: 2.1 +/- 2.5 versus 2.5 +/- 5.3 days (p = nonsignificant) and 10.8 +/- 7.1
      versus 12.8 +/- 10.6 days (p < 0.05), respectively. CONCLUSIONS: Aortic valve
      replacement can be performed safely through a partial upper sternotomy on a
      routine basis for isolated aortic valve disease.

PMID- 16631642
TI  - Aortic valve bypass for the high-risk patient with aortic stenosis.
AB  - BACKGROUND: Interest in percutaneous therapy of heart valve disease has focused
      attention on the high-risk patient with aortic stenosis. Aortic valve bypass
      (apicoaortic conduit) surgery is the construction of a vascular graft containing
      a bioprosthetic valve from the apex of the left ventricle to the descending
      thoracic aorta. We have undertaken a programmatic effort to perform aortic valve
      bypass surgery as an alternative to conventional aortic valve replacement in
      selected high-risk patients, and now report our recent experience. METHODS:
      Between April 2003 and May 2005, 14 patients with aortic stenosis underwent
      aortic valve bypass surgery at two institutions. All patients selected for aortic
      valve bypass surgery were deemed to be at very high risk for conventional aortic
      valve replacement. These patients represented 14 (5.8%) of all 243 patients
      undergoing isolated aortic valve surgery during the same time period. Mean
      Society of Thoracic Surgeons predicted risk for operative mortality (11%) was
      between the 90th and 95th percentile. RESULTS: Twelve of 14 patients had previous
      cardiac surgery with patent bypass grafts. Average age was 78 years. Mean aortic
      valve area was 0.68 cm2. All operations were performed through a left thoracotomy
      on the beating heart (cross-clamp time, 0 minutes). Cardiopulmonary bypass was
      used for 6 patients (median cardiopulmonary bypass time, 15 minutes). There were
      2 perioperative deaths. Median postoperative length of stay was 9 days. Two
      noncardiac late deaths occurred. Nine of 10 surviving patients are functional
      class I and are living independently. Early postoperative echocardiography
      confirms excellent aortic valve bypass function with preservation of ventricular
      ejection performance. CONCLUSIONS: Treatment of high-risk aortic stenosis
      patients with aortic valve bypass surgery is promising. Avoidance of sternotomy
      and cardiopulmonary bypass supports broader application to moderate-risk patients
      with aortic stenosis and as a control arm for studies of novel interventional
      therapies.

PMID- 16631643
TI  - Invited commentary.

PMID- 16631644
TI  - Midterm results of the edge-to-edge technique for complex mitral valve repair.
AB  - BACKGROUND: The edge-to-edge technique (E2E) has been advocated for the complex
      repair of myxomatous mitral valves. We compared outcomes of E2E performed in
      patients at risk for systolic anterior motion (SAM) versus outcomes in patients
      with residual mitral regurgitation (MR) after repair completion. METHODS: A total
      of 1,612 patients had repair of myxomatous mitral valves between June 1997 and
      December 2003 at Brigham and Women's Hospital. The E2E was used in 72 (4.5%)
      patients. Fifty-two patients (52/72; group I) had E2E for persistent MR after
      complex repair. Twenty patients (20/72; group II) had E2E for high risk of post
      repair SAM and left ventricular outflow tract obstruction. Mean age of the
      patients was 61 +/- 14 years; 47 were male, average New York Heart Association
      class at admission was 2.4 +/- 0.6, and mean left ventricular ejection fraction
      was 56 +/- 12%. RESULTS: The operative mortality was zero. Immediate
      postoperative MR was significantly improved in all patients compared with the
      preoperative grade (p value < 0.0005). Mean follow-up was 388 days. In those in
      whom E2E was used for residual MR without SAM risk (group I), postoperative MR (>
      or = 2+) was detected in 15 of 52 patients at 6 months. In group II, SAM was
      completely eliminated and the mean MR grade in the immediate postoperative period
      was 0.5 +/- 0.7. There was no long-term recurrence of MR in group II.
      CONCLUSIONS: This study suggests that E2E eliminates SAM and long-term MR in
      patients with pre-repair echocardiographic predictors of SAM. The E2E is not
      efficacious in preventing long-term recurrent MR if performed for residual MR
      after complex mitral repair.

PMID- 16631645
TI  - Invited commentary.

PMID- 16631646
TI  - Two hundred forty minimally invasive mitral operations through right
      minithoracotomy.
AB  - BACKGROUND: This study reports of our 7-year experience with minimally invasive
      mitral valve operations using the transthoracic clamp technique, reviewing
      morbidity and mortality as well as echocardiographic follow-up results. METHODS:
      Between 1997 and 2004, 241 patients (121 male; aged 56 +/- 14 years) underwent
      minimally invasive mitral valve surgery through right thoracotomy using the
      transthoracic clamp technique. Reconstructions were done in 199 patients, and 42
      valves were replaced. Mean length of incision was 7.0 +/- 1.2 cm. Mean
      preoperative New York Heart Association functional class was 2.6 +/- 0.9.
      RESULTS: Thirty-day mortality was 3.3% (n = 8). Operating, bypass, and cross
      clamp times averaged 241 +/- 52, 142 +/- 40, and 84 +/- 26 minutes, respectively.
      Seven patients (2.9%) had conversion to sternotomy. Nine patients (3.7%)
      underwent reexploration for bleeding. Mean intensive care unit and hospital stay
      were 18 hours and 8.1 days, respectively. Mean follow-up was 30 +/- 18 months
      (range, 3 to 76). Echocardiographic follow-up documented persistently competent
      valve function in all but 6 patients who had grade III regurgitation. Five of
      them underwent mitral valve re-reconstruction and 1 underwent transplantation. At
      76 months, freedom from nontrivial recurrent mitral regurgitation and reoperation
      were 92.3% and 96.2%, respectively. Actuarial survival at 76 months, including
      early mortality, was 90.7%. Thoracic wounds were free from infection in all
      patients. CONCLUSIONS: This study demonstrates that the direct vision,
      transthoracic clamp technique for minimally invasive mitral valve surgery is
      reproducible with low mortality and morbidity rates. It results in excellent
      cosmesis and abolished the risk of thoracic wound infection. Results are
      comparable to midterm outcomes of conventional operations.

PMID- 16631647
TI  - Mitral valve repair for anterior leaflet prolapse with expanded
      polytetrafluoroethylene sutures.
AB  - BACKGROUND: This study was a long-term Doppler echocardiographic assessment of
      mitral valve repair for anterior mitral leaflet prolapse using expanded
      polytetrafluoroethylene sutures. METHODS: Between April 1992 and December 2003,
      we performed mitral valve repair using expanded polytetrafluoroethylene sutures
      in 204 patients (mean age, 54.6 years) with severe mitral regurgitation (MR)
      having anterior mitral leaflet prolapse. The cause of valve disease was
      degenerative in 181 patients (88.7%). Postoperative serial transthoracic
      echocardiographic studies were performed in all hospital survivors. Residual MR
      flow detected by color Doppler echocardiography was classified according to the
      maximum regurgitant jet area. RESULTS: The 30-day mortality of 204 patients was
      1.4% (3 deaths). There were 12 late deaths and 14 reoperations in this series.
      Kaplan-Meier survival and freedom from reoperation at 12 years were 84.6% +/-
      4.0% and 89.9% +/- 2.9%, respectively. Postoperative transthoracic
      echocardiographic assessment after discharge (mean follow-up, 4.2 +/- 3.0 years)
      showed less than mild regurgitation (maximum regurgitant jet area < 4.0 cm2) in
      80.9% of the patients. Overall, freedom from severe MR (maximum regurgitant jet
      area > or = 7.0 cm2) estimates at 12 years were 88.1% +/- 3.1%. Freedom from
      severe MR at 12 years for 114 patients with no MR (maximum regurgitant jet area =
      0 cm2) on intraoperative transesophageal echocardiography and 77 patients with MR
      was 95.3% +/- 2.1% and 82.9% +/- 5.1%, respectively (p = 0.033). CONCLUSIONS:
      Twelve-year echocardiographic follow-up demonstrates good long-term results of
      chordal replacement with expanded polytetrafluoroethylene sutures for anterior
      mitral leaflet prolapse. To avoid recurrence of regurgitation, a significantly
      high level of competence of the valve is essential in the repair of anterior
      mitral leaflet prolapse.

PMID- 16631648
TI  - Sex-specific long-term outcomes after combined valve and coronary artery surgery.
AB  - BACKGROUND: The purpose of this study is to compare sex-specific, long-term
      outcomes after combined valve and coronary artery bypass graft surgery (CABG).
      METHODS: Between 1990 and 2000, 1,567 patients underwent combined valve and CABG
      surgery at our institution. Our surgical database was linked to a governmental
      administrative hospital discharge database and a registry of deaths to obtain
      long-term follow-up. All patients underwent CABG plus aortic (62%), mitral (31%),
      or multiple valve surgery (7%). RESULTS: Women had more preoperative risk factors
      than men (namely, hypertension, diabetes mellitus, congestive heart failure,
      atrial fibrillation, and stroke; all p < 0.001). The prevalence of triple-vessel
      disease was the same between men and women, but women received fewer mammary
      grafts and fewer total bypass grafts (both p < 0.01). Women received fewer mitral
      valve repairs and more mitral valve replacements than men (p = 0.014). Length of
      follow-up was 5.3 +/- 3.2 years (mean +/- SD; range, 0 to 12.5) and was 99.8%
      complete. Both sexes had similar long-term survival rates. Women were at higher
      risk of stroke during follow-up (risk ratio = 1.52, 95% confidence interval: 1.1
      to 2.1). There were no sex differences in rehospitalization for acute myocardial
      infarction (p = 0.9), heart failure (p = 0.4), redo cardiac surgery (p = 0.5), or
      endocarditis (p = 0.4). CONCLUSIONS: Women have a higher preoperative risk
      profile than men undergoing combined valve and CABG surgery, but long-term
      survival rates are similar. Female sex is an independent predictor of stroke
      during follow-up. Further studies should focus on the cause of increased risk of
      stroke and methods of prevention.

PMID- 16631649
TI  - Gender analysis after elective open heart surgery: a two-year comparative study
      of quality of life.
AB  - BACKGROUND: The aim of this prospective study, based on the iterative completion
      of the 36-item short form health survey questionnaire (SF36) after open heart
      surgery, was twofold: to evaluate the changes in quality of life (QOL) scores
      (over time and by gender, and also in comparison with scores from a normal
      population) and to identify possible gender differences in two-year cardiac
      functional status. METHODS: From July 2000 to July 2002, 590 elective patients
      were included in this study. Baseline and follow-up QOL surveys were obtained for
      439 patients (307 males and 132 females). The QOL scores were compared by gender,
      by analysis of variance, and by the Student t test. Factors influencing two-year
      cardiac functional status were determined by logistic regression. RESULTS: The
      comparison of baseline and follow-up scores showed a significant improvement (a
      sharp increase between baseline and year one, then stabilization) in all
      dimensions of the SF36, two years after surgery in all patients. However, QOL was
      significantly lower in women than in men in all but two dimensions; at baseline
      and during follow-up. When compared with the normal population, men and women
      over 75 had a similar QOL. The best independent predictive factor of two-year
      cardiac functional status in women was the physical component summary score and
      in men, the mental component summary score. CONCLUSIONS: The benefit of open
      heart surgery at two-year follow-up is equivalent in both genders in terms of
      QOL, although women had lower baseline QOL scores.

PMID- 16631650
TI  - Transcerebral platelet activation after aortic cross-clamp release is linked to
      neurocognitive decline.
AB  - BACKGROUND: Neurocognitive decline after cardiac surgery requiring
      cardiopulmonary bypass (CPB) may be caused in part by highly prothrombotic
      atheroemboli to the brain; the source of these emboli is likely the ascending
      aorta and aortic arch. We examined transcerebral platelet activation gradients
      using simultaneous measurements in arterial and jugular venous blood and then
      compared gradients with post-CPB-associated neurocognitive injury. METHODS:
      Eighty-one patients undergoing elective coronary artery bypass graft surgery
      requiring CPB were studied. Neurocognitive function was measured preoperatively
      and again at 6 weeks postoperatively. Paired arterial and jugular venous blood
      samples were drawn before surgery, immediately before and after aortic cross
      clamp removal (an event previously linked to embolic showers), and at the end of
      the operation. Transcerebral platelet activation gradients (venous minus arterial
      values) were compared in patients with and without cognitive deficit. RESULTS:
      Immediately after aortic cross-clamp removal, there was a significant increase in
      the transcerebral platelet activation gradient (increased % P-selectin-positive
      platelets during transcerebral passage) in the subset of patients who
      subsequently developed post-CPB cognitive deficit; this platelet activation
      gradient did not occur in patients without cognitive injury. In contrast, there
      was no transcerebral gradient of platelet activation in CPB patients as an
      entirety, nor was there a gradient at all other time points in the patient subset
      who went on to have cognitive deficit develop. This fleeting gradient of
      transcerebral platelet activation after cross-clamp removal was also
      significantly correlated with the overall change in cognitive injury score.
      CONCLUSIONS: Transient intracerebral platelet activation after removal of the
      aortic cross-clamp is associated with post-CPB neurocognitive injury.

PMID- 16631651
TI  - Transfusion in coronary artery bypass grafting is associated with reduced long
      term survival.
AB  - BACKGROUND: Perioperative red blood cell (PRBC) transfusion has been associated
      with early risk for morbid outcomes, but risk related to long-term survival has
      not been thoroughly explored. Therefore, we examined the influence of PRBC
      transfusion and component therapy on long-term survival after isolated coronary
      artery bypass grafting after controlling for the effect of demographics,
      comorbidities, operative factors, and the early hazard for death. METHODS: The US
      Social Security Death Index was used to ascertain survival status for 10,289
      patients who underwent isolated coronary artery bypass grafting from January 1,
      1995 through June 28, 2002. The outcome measure was all-cause mortality during
      the follow-up period. Unadjusted survival estimates were performed using the
      Kaplan-Meier techniques. Survival curves for transfusion status were compared
      with the log-rank test. The parametric decomposition model was used for risk
      adjusted survival. A balancing score was calculated for each patient and forced
      into the final model. RESULTS: Survival among transfused patients was
      significantly reduced as compared with nontransfused patients. The instantaneous
      risk of death displayed a biphasic pattern: a declining hazard phase from the
      time of the operation (early hazard) up until 6 months postoperatively and then a
      late hazard that continued out until about 10 years. Transfusion of red cells was
      associated with a risk-adjusted reduction in survival for both the early (0.34 +/
      0.02, p < 0.0001) and late phases (0.074 +/- 0.016, p < 0.0001). CONCLUSIONS:
      Perioperative PRBC transfusion is associated with adverse long-term sequela in
      isolated CABG. Attention should be directed toward blood conservation methods and
      a more judicious use of PRBC.

PMID- 16631652
TI  - Trends in emergency coronary artery bypass grafting after percutaneous coronary
      intervention, 1994-2003.
AB  - BACKGROUND: In the last decade, percutaneous coronary intervention (PCI) has
      undergone profound changes in techniques used to achieve revascularization and in
      patient selection. We examine trends in emergency surgical revascularization
      after PCI. METHODS: Using The Society of Thoracic Surgeons National Cardiac
      Surgery Database, we examined patients undergoing coronary artery bypass grafting
      within 6 hours of PCI from 1994 to 2003. Stratifying into groups of patients who
      had and had not suffered myocardial infarction within 24 hours of PCI followed by
      coronary artery bypass grafting (CABG), we tracked trends in characteristics,
      predicted risk, and clinical outcomes. RESULTS: The proportion of isolated CABG
      procedures done emergently after PCI decreased over 1994 to 1999 from 3,357 of
      115,679 (2.9%) to 1,227 of 155,831 (0.8%), remaining stable through 2003. Those
      suffering myocardial infarction within 24 hours made up a constant proportion of
      isolated CABG as emergency after PCI (3,352 of 1,042,864; 0.3%) since 1997. Over
      the decade, the preoperative risk profile worsened, including more elderly
      patients and more with cerebrovascular disease and congestive heart failure.
      Operative mortality among these patients has risen with time (from 8.0% to 9.3%;
      p < 0.0001 for trend), particularly in the setting of acute myocardial infarction
      (from 14.1% to 16.6%; p < 0.0001 for trend). Similarly, postoperative
      complications have increased over time, most notably seen in the need for
      reoperation (10.62% to 24.56%), prolonged postoperative ventilation (25.65% to
      54.58%), and renal failure (10.22% to 18.55%). CONCLUSIONS: In 2005, there
      remains a low but real need for emergent CABG after PCI, in which operative
      outcomes are less than ideal, especially in the postinfarction patient,
      representing an area for cross-specialty collaboration.

PMID- 16631653
TI  - Invited commentary.

PMID- 16631654
TI  - Results of the prospective multicenter trial of robotically assisted totally
      endoscopic coronary artery bypass grafting.
AB  - BACKGROUND: Robotic technology has been proven safe and efficacious in the
      performance of mitral valve repair and atrial septal defect repair. This report
      describes a Food and Drug Administration-sanctioned multicenter study of the
      safety and efficacy of the da Vinci system (Intuitive Surgical, Inc, Mountain
      View, CA) for totally endoscopic coronary artery bypass (TECAB) surgery. METHODS:
      Patients requiring left anterior descending (LAD) coronary artery
      revascularization were eligible. The procedure was performed with femoro-femoral
      cardiopulmonary bypass (CPB), endoaortic balloon occlusion, and thoracoscopy. All
      aspects of the procedure were performed with the robotic system, from internal
      mammary artery harvest to coronary anastomosis. RESULTS: Ninety-eight patients
      requiring single-vessel LAD revascularization were enrolled at 12 centers.
      Thirteen patients (13%) were excluded intraoperatively (eg, failed femoral
      cannulation, inadequate working space). In 85 patients (69 men, age 58 +/- 10
      years) who underwent TECAB, CPB time was 117 +/- 44 minutes, cross-clamp time was
      71 +/- 26 minutes, and hospital length of stay was 5.1 +/- 3.4 days. There were
      five (6%) conversions to open techniques. There were no deaths or strokes, one
      early reintervention, and one myocardial infarction (1.5%). Three-month
      angiography was performed in 76 patients, revealing significant anastomotic
      stenoses (> 50%) or occlusions in 6 patients. Overall freedom from reintervention
      or angiographic failure was 91%. CONCLUSIONS: Robotic TECAB was accomplished with
      no mortality, low morbidity, and angiographic patency and reintervention rates
      comparable with published data. Although the use of CPB was a limitation of the
      technique, this experience represents a step toward more advanced procedures,
      such as multivessel or off-pump TECAB.

PMID- 16631655
TI  - Coronary surgery in patients with preexisting chronic atrial fibrillation: early
      and midterm clinical outcome.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of
      preexisting atrial fibrillation on early and midterm clinical outcome in patients
      undergoing coronary surgery. METHODS: All elective patients undergoing coronary
      artery bypass grafting surgery between April 1996 and September 2002 were
      investigated. Patients were grouped according to their preoperative cardiac
      rhythm: sinus rhythm (SR) or preexisting atrial fibrillation (AF). In-hospital
      clinical outcomes and 5-year patient survival and cardiac-related event-free
      survival were compared using regression methods to adjust for differences between
      the groups. In all, 5,092 patients were identified, 175 (3.4%) with a history of
      preexisting AF. These patients were older (median, 64 versus 68 years) and had
      higher Parsonnet scores (median, 4 versus 8) than the SR group. Previous
      myocardial infarction, cerebrovascular accident, hypertension, diabetes mellitus,
      renal impairment, peripheral vascular disease, ejection fraction less than 50%,
      previous surgery, congestive heart failure, and use of angiotensin-converting
      enzyme inhibitors were also more common in the AF group. RESULTS: There were 60
      in-hospital deaths (1.2%), with no difference between the two groups (odds ratio
      1.02, 95% CI: 0.35 to 2.94). Atrial fibrillation patients were more likely to
      need intraoperative inotropes (p = 0.044), postoperative intra-aortic balloon
      pump (p = 0.038), and were less likely to be discharged within 6 days (p =
      0.017). The risk of death in the 5 years after surgery was higher in the AF group
      (relative risk 1.49, 95% CI: 1.06 to 2.08, p = 0.020). In the AF group, 109
      (62.2%) patients were cardioverted spontaneously by surgery, but only 69 (39.4%)
      remained in SR until discharge. Longer-term rhythm follow-up data were available
      for 48 of these 69 patients, and only 36 remained in SR at a median follow-up of
      1,483 days (interquartile range, 1,120 to 2,209). Spontaneous conversion to SR
      after surgery did not confer a midterm survival benefit (p = 0.91). CONCLUSIONS:
      Preexisting AF in patients undergoing coronary artery bypass graft surgery is not
      associated with increased in-hospital mortality and major morbidity; however, it
      is a risk factor for reduced 5-year survival. Spontaneous cardioversion to SR
      during surgery is transient in the majority of patients and is not associated
      with midterm survival benefit.

PMID- 16631656
TI  - Comparison of inflammatory responses after off-pump and on-pump coronary surgery
      using surface modifying additives circuit.
AB  - BACKGROUND: Cardiac surgery is followed by various degrees of inflammation, which
      have harmful consequences. Because of the central role of extracorporeal
      circulation (EC), off-pump coronary bypass surgery is deemed preferable. Do
      different modalities of EC challenge this view? METHODS: Four groups of similar
      patients underwent coronary surgery: (group 1) on-pump, EC with closed surface
      modifying additives (SMA) circuit and no pump suckers (n = 20); (group 2) on
      pump, EC with open SMA circuit and pump suckers (n = 20); (group 3) off-pump
      (beating heart) and heparin 3 mg/kg (n = 20); (group 4) off-pump (beating heart)
      and heparin 1 mg/kg (n = 20). Interleukins (IL)-6, IL-8, IL-10, myeloperoxidase,
      elastase, and terminal complex of the complement (TCC) were analyzed at various
      times: at induction (time I); after heparin (time II); after complete
      revascularization (time III); after protamine (time IV); and 24 hours later (time
      V). RESULTS: The TCC was significantly higher in groups 1 and 2 at time III. The
      pattern of IL-6 was the same for the four groups. No significant difference in
      myeloperoxydase content was noted; however, elastase was significantly higher in
      the two EC (on-pump) groups. CONCLUSIONS: Except for the complement system and
      elastase, on-pump surgery with SMA-coated circuits did not elicit any greater
      inflammatory response than off-pump surgery.

PMID- 16631657
TI  - Early and late outcome after off-pump coronary artery bypass graft surgery with
      coronary endarterectomy: a single-center 10-year experience.
AB  - BACKGROUND: We aimed to review the early and late results of off-pump coronary
      artery bypass graft surgery (OPCABG) with coronary endarterectomy in patients
      undergoing surgical revascularization at our institution. METHODS: Between 1995
      and 2004, of 680 OPCABG patients in a single surgeon's practice (W.R.D.), 70
      patients (10.29%) who underwent concomitant coronary endarterectomy were studied.
      The mean age was 63.6 +/- 9.29 years. Thirty-three patients (55%) were Canadian
      Cardiovascular Society class III or IV, and 24 patients (40%) were New York Heart
      Association class III or IV. Eighteen patients (35%) had impaired left
      ventricular function. The mean EuroSCORE of these patients was 5.9 +/- 1.8.
      RESULTS: Fifty-seven patients (81%) underwent right coronary artery
      endarterectomy, and 12 patients (17%) underwent left anterior descending artery
      endarterectomy (8 left interior mammary arteries used as conduits). Four patients
      (5.7%) had two vessels endarterectomized. The mean number of grafts were 2.0 +/-
      0.4. The 30-day mortality rate was 2.85% (n = 2). Three patients (4.3%) suffered
      from postoperative myocardial infarction, and 3 patients (4.3%) required
      postoperative intra-aortic balloon pump counterpulsation. Mean intensive therapy
      unit stay was 17.6 +/- 8.1 hours. Patients were extubated after a mean of 10.38
      +/- 4.9 hours. The mean length of hospital stay was 6.1 +/- 2.0 days. Fourteen
      patients (20%) had postoperative atrial fibrillation, and only 1 patient (1.42%)
      had a transient stroke with complete recovery. There were no conversions to
      cardiopulmonary bypass. A mean of 0.86 +/- 0.17 units of blood were transfused
      postoperatively. There was one reopening for bleeding, and 1 patient had renal
      failure requiring hemofiltration. The median follow-up was 4.91 years, 90% of
      patients were angina free, and the actuarial survival at 10 years was 78.04% +/-
      7.6%. CONCLUSIONS: Off-pump coronary artery bypass graft survery with coronary
      endarterectomy is feasible and achieves surgical revascularization in patients
      with diffuse coronary artery disease.

PMID- 16631658
TI  - Reduction of carbon dioxide embolism for endoscopic saphenous vein harvesting.
AB  - BACKGROUND: The endoscopic saphenous vein harvesting (EVH) introduced in coronary
      artery bypass surgery (CABG) is associated with less wound complication and
      postoperative pain. Carbon dioxide (CO2) insufflation is used during EVH to
      facilitate the procedure. The purpose of this study was to determine whether the
      incidence of CO2 embolism during EVH with CO2 insufflation could be reduced with
      lower CO2 insufflation pressure. METHODS: Four hundred and ninety-eight
      consecutive patients scheduled for elective off-pump CABG were prospectively
      studied. These patients were randomly assigned into high and low groups in which
      15 and 12 mm Hg CO2 insufflation pressures were used during EVH, respectively.
      Multiplane transesophageal echocardiography (TEE) with transgastric inferior vena
      cava view was used to monitor the appearances of CO2 bubbles. If a burst of many
      CO2 bubbles were found by TEE, the CO2 insufflation would be stopped until
      detailed examination of the operative field. RESULTS: The incidence of CO2
      embolisms in the high group of patients (13.3%) was significantly higher than
      that in the low group (6.5%, p < 0.05). Two episodes of emergent cessation of CO2
      insufflation occurred in the high group of patients. No massive CO2 embolism with
      significant hemodynamic alterations occurred in either group. CONCLUSIONS: The
      incidence of CO2 embolisms during EVH could be reduced with lower CO2
      insufflation pressure, which, in combination with increased surgical experience
      and continuous TEE monitoring of the inferior vena cava, helps to reduce the
      risks of massive CO2 embolism.

PMID- 16631659
TI  - Long-term palmar microcirculation after radial artery harvesting: an
      observational study.
AB  - BACKGROUND: The aim of this study was to assess palmar microcirculation in a long
      term follow-up after radial artery harvesting for coronary revascularization.
      METHODS: One hundred fourteen patients (100 male; aged 61.7 +/- 6.7 years;
      preoperative New York Heart Association 2.3 +/- 0.6, ejection fraction 61.4% +/-
      13.9%) were included after undergoing elective coronary revascularization using
      the radial artery of the nondominant forearm with a nonpathologic Allen's test.
      Superficial and deep tissue oxygen saturation (SO2), postcapillary venous filling
      pressure (rHb), capillary blood flow, and capillary blood flow velocity were
      determined at a mean 25 +/- 5 months after surgery using a combined laser Doppler
      spectrophotometry system. RESULTS: At 2-mm tissue depth, there was a small, but
      significant, decrease of 3% of superficial SO2 at the thumb and the thenar
      eminence (D1: 75.3% +/- 8.9% versus 77.6% +/- 9.7%, p = 0.003; thenar: 71.5% +/-
      10.5% versus 73.2% +/- 8.2%, p = 0.027). Deep palmar SO2 was changed
      significantly at 5 of 7 positions by 3%. Deep postcapillary venous filling
      pressure (8 mm) was significantly increased by 9% only at the fingertip of the
      fifth finger (112.4 +/- 49.7 versus 103.0 +/- 25.0, p = 0.033), while superficial
      capillary blood flow decreased by 13% at only 1 of 7 positions at the hypothenar
      eminence (242.0 +/- 153.6 versus 275.6 +/- 169.2, p = 0.009). Overall, only 2 of
      56 positions exceeded a given threshold of 5% change of microcirculation. No
      clinical signs of malperfusion were found (postoperative New York Heart
      Association 1.1 +/- 0.4, p < 0.05), and no patient was impaired in daily palmar
      motor activity. CONCLUSIONS: Long-term objective evaluation of superficial and
      deep palmar microcirculation confirms that radial artery harvesting for coronary
      revascularization does not compromise palmar microcirculation.

PMID- 16631660
TI  - Effect of hypoxia-reoxygenation on endothelial function in porcine cardiac
      microveins.
AB  - BACKGROUND: The cardiac venous system possesses up to 30% of total coronary
      vascular resistance and the effect of hypoxia-reoxygenation (H-R) and St Thomas
      (ST) cardioplegic solution on the vein is unknown. We investigated the effects of
      H-R, with or without ST, on endothelium-derived hyperpolarizing factor (EDHF)
      mediated relaxation in porcine cardiac microveins under clinically relevant
      temperatures. METHODS: The microveins (diameter 200 to 450 microM) mounted in a
      myograph were subjected to hypoxia (Po2 < 5 mm Hg) for 30 minutes in Krebs
      solution (n = 8) or for 60 minutes in Krebs (n = 8) or in ST at 37 degrees C (n =
      8) or 4 degrees C (n = 8), followed by 30-minute reoxygenation. The microvein was
      precontracted with thromboxane A2 mimetic U46619 (-7 log M) and the EDHF-mediated
      relaxation was induced by bradykinin (-10 to -6 log M) in the presence of
      indomethacin, NG-nitro-L-arginine, and oxyhemoglobin before and after H-R.
      RESULTS: The maximal EDHF-mediated relaxation was significantly reduced after 30
      minute hypoxia (38.7 +/- 2.0% vs 61.1 +/- 2.3%, n = 8, p < 0.001) or 60-minute
      hypoxia in either Krebs or ST at 37 degrees C (Krebs: 27.8 +/- 1.2% vs 56.6 +/-
      2.5%, n = 8, p < 0.001; ST: 23.8 +/- 4.1% vs 57.1 +/- 1.5%, n = 8, p < 0.001).
      The relaxation was significantly less after prolonged H-R in Krebs (p < 0.001).
      Incubation in Krebs or ST at 4 degrees C also reduced the EDHF-mediated
      relaxation (Krebs: 25.3 +/- 3.3%, n = 8, p < 0.001; ST: 29.1 +/- 4.4%, n = 8, p <
      0.001) and there were no significant differences between Krebs and ST regarding
      the relaxation at either 37 degrees C or 4 degrees C (p > 0.05). CONCLUSIONS: We
      conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microveins
      with more severe injury during prolonged H-R and (2) ST does not provide
      protection to the EDHF-mediated relaxation impaired by H-R at either 37 degrees C
      or 4 degrees C.

PMID- 16631661
TI  - Potassium channel-related relaxation by levosimendan in the human internal
      mammary artery.
AB  - BACKGROUND: Levosimendan is a potent inotropic and vasodilator drug used in the
      treatment of decompensated heart failure. There is no study on in vitro effects
      of levosimendan in human isolated arteries. METHODS: We investigated the effect
      of levosimendan on contractile tone of human isolated internal mammary artery
      (IMA). The responses in IMA were recorded isometrically by a force-displacement
      transducer in isolated organ baths. Levosimendan was added to organ baths either
      at rest or after precontraction with phenylephrine (1 micromol/L). Levosimendan
      induced relaxations were tested in the presence of cyclooxygenase inhibitor
      indomethacin (10 micromol/L), nitric oxide synthase inhibitor N122-nitro-L
      arginine methyl ester (100 micromol/L), large-conductance calcium-activated
      potassium-channel inhibitor tetraethylammonium (1 mmol/L), adenosine triphosphate
      sensitive potassium-channel inhibitor glibenclamide (10 micromol/L), and voltage
      sensitive potassium-channel inhibitor 4-aminopyridine (1 mmol/L). RESULTS:
      Levosimendan (10 nmol/L to 3 micromol/L) produced potent relaxation in human IMA
      (maximal effect, 75.3% +/- 4.9% of phenylephrine maximum contraction, 6.8 +/-
      0.1, n = 15; -log10 of 50% effective concentration). Vehicle had no significant
      relaxant effect. The relaxation to levosimendan is not affected by either
      potassium-channel inhibitors (tetraethylammonium and 4-aminopyridine) or
      cyclooxygenase and nitric oxide synthase inhibitors. Glibenclamide (10
      micromol/L) inhibited levosimendan-induced relaxation significantly (p < 0.01).
      CONCLUSIONS: Levosimendan effectively and directly decreases the tone of IMA. The
      mechanism of levosimendan-induced relaxation in IMA appears in part to be
      adenosine triphosphate-sensitive potassium-channel opening action. Levosimendan
      may be a cardiovascular protective agent by its relaxing action on the major
      arterial graft, IMA.

PMID- 16631662
TI  - Protamine enhances fibrinolysis by decreasing clot strength: role of tissue
      factor-initiated thrombin generation.
AB  - BACKGROUND: Excessive protamine administration to neutralize heparin after
      cardiopulmonary bypass has been implicated as a cause of postoperative
      hemorrhage. Protamine directly inhibits thrombin and tissue factor (TF)-mediated
      activation of factor VII. However, the half-life of protamine is only 4.5
      minutes; thus the purpose of this study was to determine if protamine could
      enhance fibrinolysis, explaining the delayed, protamine-associated hemorrhage
      observed in the postoperative period. METHODS: Human plasma containing 0, 6.25,
      12.5, or 25 microg/mL of protamine (n = 6 per condition) was exposed to 0.01%
      tissue factor and tissue-type plasminogen activator (tPA, 100 U/mL) for 30
      minutes, with clot growth and disintegration measured by Thromboelastograph
      (Haemoscope Corp, Skokie, IL). The TF was increased to 0.1% in additional
      experiments with plasma containing protamine (25 microg/mL) and tPA. RESULTS:
      Protamine significantly (p < 0.05) delayed the time to clot initiation, decreased
      the speed of clot propagation, and diminished clot strength in a concentration
      dependent fashion. The onset of fibrinolysis was significantly (p < 0.05)
      increased only in samples with 25 microg/mL of protamine, and the rate of clot
      lysis was not different among the conditions. The clot duration time (from
      initiation to disintegration) was significantly (p < 0.05) decreased in a
      concentration-dependent manner by protamine. Increased TF concentration (0.1%)
      significantly improved clot growth kinetics and prolonged clot duration in
      samples with 25 microg/mL of protamine compared with samples activated with 0.01%
      TF. CONCLUSIONS: Protamine enhanced fibrinolysis by decreasing clot strength by
      diminishing TF-initiated thrombin generation. Additional, clinical investigation
      is warranted to mechanistically implicate protamine-mediated enhancement of
      fibrinolysis to delayed bleeding after cardiopulmonary bypass.

PMID- 16631663
TI  - Neovasculogenic therapy to augment perfusion and preserve viability in ischemic
      cardiomyopathy.
AB  - BACKGROUND: Ischemic cardiomyopathy is a global health concern with limited
      therapy. We recently described endogenous revascularization utilizing granulocyte
      macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor
      cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha
      (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and
      enhancement of myocardial function was observed. In this study we examined the
      regional biologic mechanisms underlying this therapy. METHODS: Lewis rats
      underwent left anterior descending coronary artery (LAD) ligation and developed
      ischemic cardiomyopathy over 6 weeks. Three weeks after ligation, the animals
      received either subcutaneous GMCSF and intramyocardial SDF injections or saline
      injections as control. Six weeks after LAD ligation circulating EPC density was
      studied by flow cytometry. Quadruple immunofluorescent vessel staining for
      mature, proliferating vasculature was performed. Confocal angiography was
      utilized to identify fluorescein lectin-lined vessels to assess perfusion.
      Ischemia reversal was studied by measuring myocardial adenosine triphosphate
      (ATP) levels. Myocardial viability was assayed by terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling detection of
      apoptosis and quantitation of myofilament density. RESULTS: The GMCSF/SDF therapy
      enhanced circulating leukocyte (13.1 +/- 4.5 x 10(6) vs 3.1 +/- 0.5 x 10(6)/cc, p
      = 0.001, n = 6) and EPC (14.2 +/- 6.6 vs 2.2 +/- 2.1/cc, p = 0.001, n = 6)
      concentrations. Tetraimmunofluorescent labeling demonstrated enhanced stable
      vasculature with this therapy (39.2 +/- 8.1 vs 25.4 +/- 5.1%, p = 0.006, n = 7).
      Enhanced perfusion was shown by confocal microangiography of borderzone lectin
      labeled vessels (28.2 +/- 5.4 vs 11.5 +/- 3.0 vessels/high power field [hpf], p =
      0.00001, n = 10). Ischemia reversal was demonstrated by enhanced cellular ATP
      levels in the GMCSF/SDF borderzone myocardium (102.5 +/- 31.0 vs 26.9 +/- 4.1
      nmol/g, p = 0.008, n = 5). Borderzone cardiomyocyte viability was noted by
      decreased apoptosis (3.2 +/- 1.4% vs 5.4 +/- 1.0%, p = 0.004, n = 10) and
      enhanced cardiomyocyte density (40.0 +/- 5.6 vs 27.0 +/- 6 myofilaments/hpf, p =
      0.01, n=10). CONCLUSIONS: Endogenous revascularization for ischemic
      cardiomyopathy utilizing GMCSF EPC upregulation and SDF EPC chemokinesis
      upregulates circulating EPCs, enhances vascular stability, and augments
      myocardial function by enhancing perfusion, reversing cellular ischemia, and
      increasing cardiomyocyte viability.

PMID- 16631664
TI  - Invited commentary.

PMID- 16631665
TI  - Cognitive dysfunction in advanced heart failure and prospective cardiac assist
      device patients.
AB  - BACKGROUND: Extended periods of hypoperfusion in an advanced heart failure (HF)
      places patients at high risk for neurobehavioral compromise, which has not been
      studied systematically. It is also not clear how intravenous inotropic therapy
      and mechanical cardiac assist devices (MCAD) affect cognitive function. METHODS:
      This prospective cross-sectional cognitive preliminary study evaluated 252
      potential heart transplant candidates assessing functions in memory, motor, and
      processing speed. Patients were divided into three HF groups based on severity of
      disease: group 1 outpatients (n = 113), group 2 in-patients requiring inotropic
      infusion (n = 83), and group 3 inpatients likely requiring MCAD support (n = 56).
      Aggregate z-scores for memory, motor, and processing speed and independent
      samples t tests assessed intergroup differences on 13 cognitive measures.
      RESULTS: A broad pattern of cognitive impairment was observed within the advanced
      HF group; fewer deficits were found in group 1 outpatients and more severe
      deficits in group 3 MCAD subjects. A difference in motor functions was observed
      as the earliest abnormality, with group 3 showing significant changes compared
      with group 1. The most dramatic changes were seen in domain mental processing
      speed along with specific verbal and visual memory functions, which were slower
      in group 3 compared with groups 1 and 2. CONCLUSIONS: Cognitive deficits are
      common in advanced HF and worsen with increasing severity of HF. Appropriately
      designed and randomized studies will be needed to demonstrate if earlier MCAD
      implantation is warranted to arrest cognitive dysfunction and better
      postimplantation adaptation.

PMID- 16631666
TI  - Relationship between renal function and left ventricular assist device use.
AB  - BACKGROUND: Poor renal function may affect outcomes after left ventricular assist
      device (LVAD) placement. Conversely, LVADs may optimize circulation and improve
      renal function. METHODS: To assess the relationship between renal function and
      LVAD use, changes in creatinine clearances (CrCl, in mL/min) were assessed
      retrospectively in 220 patients who underwent LVAD placement. These patients were
      also divided into four groups based on CrCl quartiles (< 47, 48-68, 69-95, and >
      95) and compared for outcomes post-LVAD placement. RESULTS: Eighty-four patients
      died on LVAD support. Survival on LVAD was worse for patients with the worst
      baseline CrCl (42%, 52%, 63%, and 79% for 6 month and 26%, 34%, 47%, and 66% for
      12 month survival for quartiles 1-4; both p < 0.01 for trend). Adjusting for
      other covariates, patients in the lowest CrCl quartile were at a higher risk of
      dying postimplant (odds ratio 1.95, 95% confidence interval 1.14-3.63). Paired
      sample analysis showed the following changes in CrCl: preoperative to week 1,
      77.0 +/- 46.6 to 92.1 +/- 51.1 (p < 0.01; n = 202), week 1 to 2, 89.4 +/- 49.2 to
      95.2 +/- 52.4 (p = 0.01, n = 171), week 2 to 3, 107.5 +/- 58.1 to 113.7 +/- 66.1
      (p = 0.16, n = 74), and week 3 to 4, 111.1 +/- 56.6 to 110.5 +/- 56.8 (p = 0.87,
      n = 60). For the 60 patients with baseline CrCl less than 50, CrCl increased from
      36.7 +/- 9.2 to 60.1 +/- 35.5 (p < 0.01; n = 55 pairs) from preimplant to week 1.
      In 37 of these patients (62%) on intraaortic balloon pump support preimplant,
      CrCl increased from 38.4 +/- 8.2 to 67.9 +/- 40.3 mL/minute (p < 0.01) during
      week 1 postimplant. Recovery of renal function to CrCl greater than 50 was
      associated with a trend towards better 30-day survival (84% vs 66%, p = 0.09).
      CONCLUSIONS: Baseline poor renal function is associated with worse outcomes after
      LVAD implantation. However, renal function improves substantially and rapidly in
      post-LVAD survivors and is associated with improved outcomes. These data
      underscore the importance of careful patient selection for LVAD therapy.

PMID- 16631667
TI  - Mechanical reliability of the Jarvik 2000 Heart.
AB  - BACKGROUND: Device failure is a limitation of permanent mechanical circulatory
      support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial
      flow pump with ceramic bearings designed to provide more than 10 years'
      durability. METHODS: The Jarvik 2000 Heart was implanted in 102 patients between
      April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were
      implanted as a bridge-to-transplantation, and 19 with postauricular power supply
      as lifetime therapy. Eighteen pumps were recovered intact after clinical use and
      run continuously on the bench to further assess durability. RESULTS: No
      implantable component failure occurred either in patients or during bench
      testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and
      51 years in vitro. The mean support time for bridge-to-transplant recipients was
      159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients
      were supported moer than 2 years, with the longest ongoing approaching 5 years.
      External cables caused three system failures, with a 95% freedom from system
      failure at 4 years. Device malfunctions, related to external cables (9) and lack
      of a backup battery (1), caused no adverse consequences. Before introduction of
      noncorrosive, gold-plated stainless steel connectors, corrosion was observed on
      three connectors to the retroauricular power supply. CONCLUSIONS: The Jarvik 2000
      Heart has had no implantable component failure. Meaningful durability data and
      failure mode can only be established by real-time testing in patients. The
      reliability and dependability of this device, in addition to the exchangeability
      of external components, give promise for long-term circulatory support in
      critically ill heart failure patients.

PMID- 16631668
TI  - Multimedia-driven teaching significantly improves students' performance when
      compared with a print medium.
AB  - BACKGROUND: In this study, we compared the educational value of a multimedia
      module about aortic valve replacement as a preparation for the operating room
      with a print medium of identical content. METHODS: One hundred twenty-six
      students were randomly assigned in a prospective study to either use the
      multimedia course (n = 69) or a print version (n = 57). A 20-item multiple-choice
      test was performed before and after learning with the respective medium. Both
      groups participated in an operation during which they were evaluated with 28
      standardized tasks and questions. Individual motivation, computer literacy, and
      didactic quality of both media were assessed with psychometric tests. RESULTS:
      There were no significant differences in the multiple-choice pretest (multimedia,
      30.6% +/- 12.4% versus print, 27.9% +/- 11.4%) and posttest responses
      (multimedia, 76.7% +/- 13.3% versus print, 76.9% +/- 11.1). Mean percentage of
      correct answers during the operation was 82.9% +/- 10% in the online group and
      64.7% +/- 12% in the print group (p < 0.0001). The multimedia group needed
      significantly (p < 0.001) less study time (105 +/- 24 minutes) when compared with
      the text group (122 +/- 30 minutes). There were no statistically significant
      differences in motivation, computer literacy, and didactic quality of either
      medium. CONCLUSIONS: Regarding factual knowledge, there is no difference between
      multimedia-driven learning and a print medium. During heart operations, when
      understanding of complex temporal and spatial events is essential, students'
      performance is significantly improved by multimedia-enhanced teaching. The latter
      further proved to be more efficient in terms of study time.

PMID- 16631669
TI  - Invited commentary.

PMID- 16631670
TI  - The Cardiac Surgery Advanced Life Support Course (CALS): delivering significant
      improvements in emergency cardiothoracic care.
AB  - BACKGROUND: A 3-day cardiac surgery advanced life support course was designed
      with a series of protocols to manage critically ill cardiac surgical patients and
      patients who suffer a cardiac arrest. We sought to determine the effect of this
      course on the management of simulated critically ill and cardiac arrest patients.
      METHODS: Twenty-four candidates participated in the course. Critically ill
      patients were simulated using intubated mannikins, with lines and drains in situ,
      and a laptop with an intensive care unit monitor simulation program. Candidates
      were tested before and after the course with rigidly predesigned clinical
      situations. Candidates were split into groups of 6, and cardiac arrests were
      simulated in the same fashion, with all required surgical equipment immediately
      available. All scenarios were videotaped, and after blinding, an independent
      surgeon assessed the times to achieve predetermined clinical endpoints. RESULTS:
      The time to successful definitive treatment was significantly faster postcourse
      for the critically ill patient scenarios: (565 secs [SD 27 secs] precourse,
      compared with 303 secs [SD 24 secs] postcourse; p < 0.0005). In addition, the
      times taken to achieve a wide range of predetermined objectives, including airway
      check, assessing breathing, circulation assessment, treating with oxygen,
      appropriate treatment of the circulation, and requesting blood gases, chest
      radiographs, and electrocardiograms, were also significantly faster in the
      postcourse scenarios. Times to successful chest reopening and internal cardiac
      massage were also significantly improved in cardiac arrest patients: (451 secs
      [SD 39 secs] precourse and 228 secs [SD 17 secs] postcourse; p = 0.011).
      CONCLUSIONS: Structured training and practice in the management of critically ill
      cardiac surgical patients and patients suffering a cardiac arrest leads to
      significant improvements in the speed and quality of care for these patients.

PMID- 16631671
TI  - Favorable long-term outcome of Maze surgery in patients with lone atrial
      fibrillation.
AB  - BACKGROUND: Rhythm control is indicated for patients suffering from symptomatic
      atrial fibrillation (AF), but remains difficult to establish. We investigated the
      long-term outcome of Cox maze III surgery in patients with symptomatic lone AF
      refractory to antiarrhythmic drug therapy. METHODS: Patients with a history of
      symptomatic paroxysmal or persistent AF refractory for at least two class I or
      III antiarrhythmic drugs and without structural heart disease or bradyarrhythmias
      were included. All patients underwent Cox maze III surgery. Complete success was
      defined as the absence of AF without antiarrhythmic drugs beyond 3 months after
      the procedure, and partial success as the absence of AF with antiarrhythmic drug
      use. RESULTS: A total of 29 patients were included (27 male), with a mean age of
      48 +/- 6 years. At the time of surgery, 11 patients (38%) had persistent AF.
      After a mean follow-up of 4.8 +/- 2.4 years, 79% of patients had complete
      success, and 2 patients (7%) were free of AF with antiarrhythmic drugs. At the
      end of follow-up, left ventricular fractional shortening was significantly
      improved (from 31% +/- 10% to 39% +/- 8%, p = 0.002), left atrial size was
      unchanged, exercise capacity was within normal ranges, and quality of life was
      comparable with that of healthy controls. Severe complications included
      reoperations for postoperative bleeding (n = 3), pericardial effusion (n = 1),
      and mediastinitis (n = 1). In 2 patients, a pacemaker was implanted
      postoperatively because of sinus node dysfunction. CONCLUSIONS: Cox maze III
      surgery is a highly effective therapy for drug-refractory lone AF, and therefore
      remains an alternative to transvenous pulmonary vein ablation.

PMID- 16631672
TI  - Right-sided Maze procedure for atrial tachyarrhythmias in congenital heart
      disease.
AB  - BACKGROUND: Congenital heart disease (CHD) that causes right atrial dilatation is
      commonly associated with atrial flutter and/or fibrillation (AFl/F). To reduce
      late recurrence of AFl/F in patients undergoing repair of CHD, we utilized a
      concomitant right-sided maze procedure. METHODS: From 1993 to 2003, 99 patients
      with CHD and associated AFl/F underwent a concomitant right-sided maze procedure
      at the time of CHD repair. Ages ranged from 9 to 72 years (median, 43 years).
      Atrial flutter and/or fibrillation was paroxysmal in 81 and chronic in 18;
      duration ranged from less than 1 month to 39.5 years (median, 2.9 years). Primary
      cardiac diagnoses were Ebstein anomaly (n = 47), other congenital tricuspid
      regurgitation (n = 19), univentricular heart (n = 11), isolated atrial septal
      defect (ASD, n = 8), tetralogy of Fallot (n = 8), and other (n = 6). RESULTS:
      Other concomitant procedures included tricuspid valve repair or replacement (n =
      70), ASD closure (n = 39), and pulmonary valve procedures (n = 18). There were 6
      early deaths. At hospital dismissal, 83 patients were free of AFl/F and 63 were
      in sinus rhythm. Follow-up in 87 of the 93 early survivors extended up to 8 years
      (mean, 2.7 years). There were 4 late deaths, all from noncardiac causes. Of the
      83 known late survivors, 77 (93%) were free of AFl/F. Eighty-two of the 83
      survivors were in New York Heart Association class I or II. CONCLUSIONS: In
      patients with AFl/F associated with CHD, a concomitant right-sided maze procedure
      at the time of intracardiac repair is effective in reducing late recurrent AFl/F.
      Most patients enjoy an excellent quality of life.

PMID- 16631673
TI  - Outcomes after late reoperation in patients with repaired tetralogy of Fallot:
      the impact of arrhythmia and arrhythmia surgery.
AB  - BACKGROUND: We evaluated outcomes in patients requiring late reoperation after
      tetralogy of Fallot (ToF) repair to identify risk factors for arrhythmia and
      determine whether arrhythmia surgery decreased the risk of subsequent death or
      recurrent arrhythmia. METHODS: Review was performed of all ToF patients from 1969
      to 2005 undergoing reoperation late (> 1 year) after repair. Patients with
      associated lesions, except pulmonary atresia, were included. A total of 249
      patients had 278 reoperations. Procedures at initial reoperation included
      pulmonary valve replacement (PVR) in 217, ablation in 63, and tricuspid valve
      repair/replacement in 46. Pre-reoperative arrhythmias were present in 75,
      including supraventricular tachycardia (SVT) in 31, ventricular tachycardia (VT)
      in 34, and SVT+VT in 10 patients. RESULTS: Median age at reoperation was 23 years
      (range, 1 to 63). Ten-year survival after reoperation was 93%, and was
      independent of arrhythmia status (p = 0.86). Arrhythmia patients were
      characterized by older age at initial repair and at late reoperation, tricuspid
      and pulmonary regurgitation, and longer QRS duration (p < 0.001 for all). Risk
      factors for post-reoperative recurrent arrhythmia were longer QRS duration and
      not having PVR. Longer QRS duration, with a cut-point of more than 160 msec, was
      associated with recurrent SVT (p = 0.004). Supraventricular tachycardia ablation
      improved arrhythmia-free survival (75% versus 33%, p < 0.001) but VT ablation did
      not (96% versus 95%, p = 0.50). However, recurrent VT occurred in only 3 patients
      (10%). CONCLUSIONS: Late mortality in patients undergoing reoperation after ToF
      repair is not impacted by pre-reoperative arrhythmia. Prolongation of QRS
      identifies patients at risk for recurrent VT and SVT, but recurrent VT is
      uncommon. Early PVR, and surgical ablation in patients with SVT, decreases
      arrhythmic risk.

PMID- 16631674
TI  - Comprehensive Aristotle score: implications for the Norwood procedure.
AB  - BACKGROUND: Aristotle score is emerging as a reliable tool to measure surgical
      performance. We estimated the comprehensive Aristotle score for the Norwood
      procedure, correlated it with survival, and considered its impact on surgical
      management of hypoplastic left heart syndrome. METHODS: Comprehensive Aristotle
      score was retrospectively calculated for 39 consecutive Norwood procedures
      performed from 2001 to 2004. Survival was estimated by the Kaplan-Meier method.
      RESULTS: The Aristotle scores ranged from 14.5 to 23.5 (mean, 19.12 +/- 2.52;
      median, 19.5). The score was 20 or greater in 44% (17 of 39) of cases. The most
      frequent patient-adjusted factors were aortic atresia (n = 16), interrupted
      aortic arch (n = 9), mechanical ventilation to treat cardiorespiratory failure (n
      = 19) and shock resolved at time of surgery (n = 13). Hospital mortality was
      58.8% (10 of 17) in case of score of 20 or more and 9.1% (2 of 22) for score less
      than 20 (p = 0.0014). From 2003 on, all patients with a score less than 20
      survived. Actuarial estimate of survival at 1 year is 56.2% +/- 7.9% and there
      have been no late deaths after 1 year. One-year survival is much lower (p =
      0.001) for patients with scores of 20 or greater (29.4% +/- 11.05%) compared with
      those whose scores were less than 20 (77.3% +/- 8.9%). CONCLUSIONS: This study
      shows significant correlation of comprehensive Aristotle score with hospital
      mortality and late survival after Norwood palliation. It suggests that operative
      survival on the order of 90% may be achieved in patients with comprehensive
      complexity scores of less than 20. Efforts should be devoted to improve survival
      of high-risk patients (score > or = 20).

PMID- 16631675
TI  - Invited commentary.

PMID- 16631676
TI  - The Lecompte maneuver for relief of airway compression in absent pulmonary valve
      syndrome.
AB  - BACKGROUND: Congenital absence of the pulmonary valve syndrome (APVS) is a rare
      cardiac defect characterized by aneurysmal pulmonary arteries, hypoplastic
      pulmonary valve cusps, and tracheobronchial abnormalities. Absence of the
      pulmonary valve syndrome usually occurs in conjunction with ventricular septal
      defect (VSD) and right ventricular outflow tract obstruction (RVOTO). Surgical
      mortality rates as high as 16% to 56% have been reported. Here, we describe the
      surgical results using the Lecompte maneuver, reduction pulmonary arterioplasty,
      and a valved right ventricle to pulmonary artery (RV-PA) conduit. METHODS:
      Medical records and operative and echocardiography reports for all surgical APVS
      cases were retrospectively examined for pertinent clinical variables. A patient
      with left bronchial compression due to enlarged pulmonary arteries associated
      with totally anomalous pulmonary venous drainage (TAPVD) is included to
      illustrate the value of the Lecompte maneuver. RESULTS: From January 2002 to
      December 2004, 4 children with APVS had surgery at a median age of 5 months
      (range, 3 months to 3.5 years). Three had malalignment VSD and RVOTO. Four had
      respiratory signs (cough, wheeze, tachypnea, oxygen dependence, ventilator
      dependence), and all 5 had evidence of tracheobronchial compression by computed
      tomography or magnetic resonance imaging. Repair included a Lecompte maneuver, a
      valved conduit with reduction pulmonary arterioplasty, and VSD closure as
      necessary. The TAPVD patient had repair of the anomalous veins and a Lecompte
      maneuver. There have been no deaths, and all patients were discharged in good
      condition. Follow-up is complete at a median of 24 months (range, 9 to 35).
      Echocardiography has shown no progressive enlargement of the pulmonary arteries.
      CONCLUSIONS: Use of the Lecompte maneuver, reduction arterioplasty, and a valved
      conduit for repair of APVS provides favorable early and midterm results.

PMID- 16631677
TI  - Biventricular repair for right atrial isomerism.
AB  - BACKGROUND: Biventricular repair is often difficult to accomplish in patients
      with right atrial isomerism because of complex anomalous structures. METHODS: Ten
      patients with right atrial isomerism underwent biventricular repair. Their ages
      ranged from 15 months to 21 years. The follow-up period ranged from 1 month to 21
      years. The Fontan procedure was unsuitable in 7 patients. The atrioventricular
      valves were separated in 5 patients and common in 5. One patient who had severe
      right-sided atrioventricular valvular regurgitation required concomitant
      prosthetic valve replacement. Another patient with a hypoplastic intraventricular
      septum underwent ventricular septation. Nine patients had two balanced
      ventricles. A ventricular septal defect was enlarged for rerouting in 3 patients.
      All patients had anomalous venoatrial connections and required intra-atrial
      baffle rerouting. One with major aortopulmonary collateral arteries underwent
      staged unifocalization. Three had extracardiac conduit repair. The outcomes were
      compared with 97 patients who underwent the Fontan procedure. RESULTS: There were
      3 early deaths and 1 late death. Six survivors are in New York Heart Association
      functional class I or II. Two are free from medications. Two required reoperation
      owing to infection or prosthetic valve failure. At 1 year, cardiac index and
      systemic venous pressure were 3.2 +/- 0.9 L.min(-1).m(-2) and 6.6 +/- 1.6 mm Hg,
      respectively. There were no significant differences in survival, freedom from
      arrhythmia, freedom from reoperation, or exercise tolerance between biventricular
      repair and the Fontan procedure. CONCLUSIONS: Biventricular repair provided good
      long-term outcomes in patients with right atrial isomerism. In selected
      circumstances, biventricular repair is an acceptable alternative to the Fontan
      procedure.

PMID- 16631678
TI  - Preservation of mitochondrial structure and function after cardioplegic arrest in
      the neonate using a selective mitochondrial KATP channel opener.
AB  - BACKGROUND: Mitochondrial dysfunction may contribute to early postoperative
      neonatal heart dysfunction. Diazoxide, a mitochondrial-selective adenosine
      triphosphate-sensitive potassium-channel opener, is associated with mitochondrial
      preservation after cardioplegic arrest. We evaluated the mitochondrial-protective
      effect of diazoxide in terms of mitochondrial structure and function after
      neonatal cardioplegic arrest. METHODS: Newborn piglets (age, approximately 14
      days) underwent cardiopulmonary bypass and 60 minutes of cardioplegic arrest
      using cold crystalloid cardioplegic solution (CCP, n = 5) or cold crystalloid
      cardioplegic solution with diazoxide (CCP+D, n = 5). After 6 hours of recovery,
      myocardium was harvested. Control myocardium from piglets that did not undergo
      cardiopulmonary bypass (non-CPB, n = 5) was obtained. RESULTS: Cardioplegic
      arrest was associated with translocation of Bax to the mitochondria, which was
      not prevented by diazoxide. Nevertheless, by electron microscopy, CCP-associated
      remodeling of mitochondrial structure was subjectively diminished in CCP+D
      hearts. In addition, CCP-associated mitochondrial permeabilization and cytochrome
      c release into the cytosol were prevented with CCP+D (p < 0.05). In vitro oxygen
      consumption of isolated mitochondria demonstrated deficient function of
      mitochondrial complex I in CCP, but it was preserved in the CCP+D myocardial
      mitochondria (p < 0.05). Complex II and IV activity was not different among
      groups. In parallel with impaired complex I function, the cardiac adenosine
      triphosphate content was diminished in CCP hearts, but well maintained in CCP+D
      hearts (p < 0.05). CONCLUSIONS: Although early apoptotic signaling events (Bax
      translocation) are not prevented by diazoxide, addition of the mitochondrial
      selective adenosine triphosphate-sensitive potassium-channel opener to the
      cardioplegic solution is associated with protection of mitochondrial structural
      and functional integrity in a clinically relevant model of neonatal cardiac
      surgery. The mitochondrial-protective effects of diazoxide may contribute to
      improved postoperative myocardial function in the neonate.

PMID- 16631679
TI  - Prevalence of benign disease in patients undergoing resection for suspected lung
      cancer.
AB  - BACKGROUND: In this era of expanded lung cancer screening, accurate
      differentiation of benign from malignant lesions remains an important problem. We
      sought to characterize our experience with focal pulmonary lesions suggestive of
      lung cancer and subsequently proven benign on surgical resection. METHODS: A
      retrospective analysis was performed on 1,560 patients who underwent resection
      for focal pulmonary lesions at our institution from January 1995 to December
      2002. Computed tomography and pathology reports were reviewed for all patients.
      Fluorine-18-fluorodeoxyglucose positron emission tomography studies were
      performed on 43 patients. RESULTS: Benign processes were found on pathologic
      examination in 140 patients (9%). Resection was accomplished by thoracotomy in
      103 patients (74%), video-assisted thoracoscopy in 36 patients (26%), and
      sternotomy in 1 patient (0.7%). Seventy patients (50%) underwent mediastinoscopy
      before resection. There was 1 (0.7%) perioperative death. Pathologic diagnoses
      from the pulmonary resections revealed granulomatous inflammation in 91 patients
      (65%), hamartoma in 17 patients (12%), pneumonia or pneumonitis in 14 patients
      (10%), fibrosis in 5 patients (4%), and other in 13 patients (9%). Fluorine-18
      fluorodeoxyglucose positron emission tomography imaging suggested malignancy in
      22 of 43 patients and benign lesion in 20 of 43 patients (1 study was not
      interpretable). Thirty-eight patients underwent needle biopsy before surgery. Of
      these, 29 samples were nondiagnostic, 5 samples were negative, and 4 samples were
      considered positive for malignancy. CONCLUSIONS: Despite thorough clinical
      assessment, advanced imaging technology, and needle biopsy, many patients
      continue to undergo surgery for benign disease. Aggressive attempts to diagnose
      and treat early stage lung cancer must be tempered with this understanding.

PMID- 16631680
TI  - Operative mortality and respiratory complications after lung resection for
      cancer: impact of chronic obstructive pulmonary disease and time trends.
AB  - BACKGROUND: Smoking is a common risk factor for chronic obstructive pulmonary
      disease (COPD), cardiovascular disease, and lung cancer. In this observational
      study, we examined the impact of COPD severity and time-related changes in early
      outcome after lung cancer resection. METHODS: Over a 15-year period, we analyzed
      an institutional registry including all consecutive patients undergoing surgery
      for lung cancer. Using the receiver-operating characteristic (ROC) curve, we
      analyzed the relationship between forced expiratory volume in 1 second (FEV1) and
      postoperative mortality and respiratory morbidity. Multiple regression analysis
      has also been applied to identify other risk factors. RESULTS: A preoperative
      FEV1 less than 60% was a strong predictor for respiratory complications (odds
      ratio [OR] = 2.7, confidence interval [CI]: 1.3 to 6.6) and 30-day mortality (OR
      = 1.9, CI: 1.2 to 3.9), whereas thoracic epidural analgesia was associated with
      lower mortality (OR = 0.4; CI: 0.2 to 0.8) and respiratory complications (OR =
      0.6; CI: 0.3 to 0.9). Mortality was also related to age greater than 70 years,
      the presence of at least three cardiovascular risk factors, and pneumonectomy.
      From the period 1990 to 1994, to 2000 to 2004, we observed significant reductions
      in perioperative mortality (3.7% versus 2.4%) and in the incidence of respiratory
      complications (18.7% versus 15.2%), that was associated with a higher rate of
      lesser resection (from 11% to 17%, p < 0.05) and increasing use of thoracic
      epidural analgesia (from 65% to 88%, p < 0.05). CONCLUSIONS: Preoperative FEV1
      less than 60% is a main predictor of perioperative mortality and respiratory
      morbidity. Over the last 5-year period, diagnosis of earlier pathologic cancer
      stages resulting in lesser pulmonary resection as well as provision of continuous
      thoracic epidural analgesia have contributed to improved surgical outcome.

PMID- 16631681
TI  - Invited commentary.

PMID- 16631682
TI  - Therapeutic bronchoscopy interventions before surgical resection of lung cancer.
AB  - BACKGROUND: Therapeutic bronchoscopy is used for endobronchial staging of lung
      cancer and symptomatic relief of central airway obstruction or postobstructive
      pneumonia. The aim of this study was to assess the utility of therapeutic
      bronchoscopy as a complementary tool in the combined bronchoscopic and surgical
      management of malignant airway lesions before curative lung surgery. METHODS:
      Seventy-four consecutive patients with nonsmall cell lung carcinoma undergoing a
      therapeutic bronchoscopy procedure followed by surgery with a curative intent
      were included. RESULTS: A single interventional bronchoscopic method was used in
      27 patients (36%) and a combination of methods in 47 patients (64%). Median
      forced expiratory volume in 1 second (FEV1) before and after bronchoscopy were
      1.7 L and 2.2 L, respectively, and forced vital capacity (FVC) was 2.5 L and 3.3
      L, respectively. Sleeve upper lobectomy was performed in 22 patients (30%),
      sleeve upper bilobectomy in 16 patients (22%), lower bilobectomy in 2 patients
      (3%), pneumonectomy with sleeve resection in 2 patients (3%), and pneumonectomy
      in 28 patients (38%). The following surgeries were performed in 1 patient each:
      sleeve middle lobectomy, sleeve lower lobectomy, carina resection and complex
      reconstruction, and exploratory thoracotomy. Overall, parenchyma-sparing surgery
      (lobectomy or bilobectomy) could be performed in 57% patients after therapeutic
      bronchoscopy. There were no in-hospital deaths or deaths in the first 30 days
      after surgery. CONCLUSIONS: Therapeutic bronchoscopy can be used as a
      complementary tool in the combined bronchoscopic and surgical management of
      malignant airway obstruction before curative lung surgery. Therapeutic
      bronchoscopy might permit parenchyma-sparing surgery in patients with lung
      cancer.

PMID- 16631683
TI  - Cytokine profile after lung transplantation: correlation with allograft injury.
AB  - BACKGROUND: Post-lung transplant reperfusion edema (PLTRE) and its more severe
      form, primary graft failure (PGF), occur in 10% to 60% of lung transplant
      recipients. We hypothesized that PLTRE and PGF would be associated with an
      elevated proinflammatory cascade and that the allograft would be the source of
      cytokine appearance in the circulation. METHODS: Pulmonary arterial and systemic
      arterial samples were obtained at baseline and at 4, 8, and 24 hours after
      reperfusion. Post-lung transplant reperfusion-edema and PGF were defined as
      PaO2/FiO2 less than 300 with a mild or moderate infiltrate, or less than 200 with
      a severe infiltrate and ventilator dependence after 72 hours, respectively. Tumor
      necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-10
      concentrations were determined by immunoassay. RESULTS: Fifteen single and 6
      bilateral lung recipients were studied. Six (29%) had PLTRE and 4 (19%) had PGF;
      these patients had an overall elevation in plasma IL-6, IL-8, and IL-10
      concentrations (all p < 0.05). Subgroup analysis revealed a significantly greater
      elevation in IL-6, IL-8, and IL-10 levels in PGF patients (all p < 0.01) versus
      PLTRE. In the PGF group, TNFalpha and IL-10 concentrations were significantly
      greater in the systemic versus the pulmonary arterial samples (p < 0.05).
      CONCLUSIONS: Patients with PLTRE and PGF exhibited graded increases in IL-6, IL
      8, and IL-10 concentrations. The PGF patients had higher TNFalpha and IL-10
      systemic arterial concentrations overall, consistent with the allograft being a
      source of this cytokine production.

PMID- 16631684
TI  - Lamivudine prophylaxis for hepatitis B virus infection after lung
      transplantation.
AB  - BACKGROUND: Several reports have shown the efficacy of prophylactic lamivudine
      treatment for hepatitis B virus (HBV) infection in liver and renal
      transplantations. No data are available, however, after lung transplantation. We
      report our experience with prophylactic lamivudine treatment in lung transplant
      recipients with HBV infection or when the donor was HBc antibody positive.
      METHODS: All our 120 lung transplant recipients and their donors were routinely
      screened for HBV markers. All recipients who tested positive for hepatitis B
      surface antigen and negative for HBV-DNA, or had organs from donors who tested
      positive for hepatitis B core antibody, were treated prophylactically with
      lamivudine for 12 months after lung transplantation. Patients whose liver
      functions became abnormal during follow-up were tested for HBV serology and HBV
      DNA. RESULTS: Eleven of 120 lung transplant recipients (9.2%) were treated with
      prophylaxis lamivudine. Four recipients were hepatitis B surface antigen
      positive, and 7 recipients received organs from donors positive for HBc
      antibodies. Median follow-up after treatment was 24 months. All patients had
      normal alanine transaminase and undetectable levels of HBV-DNA before treatment.
      No side effects of lamivudine therapy were reported by any of the patients.
      Reactivation with alanine transaminase elevation and high HBV-DNA levels occurred
      in 2 patients. Both of them were recipients positive for hepatitis B surface
      antigen. In the first patient, lamivudine-resistant strain was detected and
      adefovir dipivoxil was started. In the other, reactivation developed 2 months
      after the end of lamivudine treatment. Lamivudine treatment was resumed, with
      rapid normalization of the HBV-DNA. CONCLUSIONS: Use of lamivudine is considered
      safe for suppressing HBV infection after lung transplantation.

PMID- 16631685
TI  - Functional and physiologic results of video-assisted thoracoscopic diaphragm
      plication in adult patients with unilateral diaphragm paralysis.
AB  - BACKGROUND: Plication of the hemidiaphragm for unilateral diaphragm paralysis is
      infrequently performed in adults. Barriers to diaphragm plication have included
      the perceived need for thoracotomy and uncertainty of the potential benefits. The
      purpose of this investigation was to assess the effects of video-assisted
      thoracoscopic diaphragm plication in symptomatic adult patients with unilateral
      diaphragm paralysis. METHODS: Patients with unilateral diaphragm paralysis
      underwent an evaluation that included a chest radiograph, fluoroscopic sniff
      test, pulmonary spirometry, and the Medical Research Council (MRC) dyspnea score.
      Patients with symptomatic unilateral diaphragm paralysis present for at least 6
      months were offered video-assisted thoracoscopic diaphragm plication. Patients
      who underwent diaphragm plication as well as those who declined surgery were
      reassessed at 6 months with a chest radiograph, spirometry, and the MRC dyspnea
      score. RESULTS: Twenty-five patients underwent left (19) or right (6) diaphragm
      plication through video-assisted thoracoscopic diaphragm plication (22) or
      thoracotomy (3). There were no operative deaths. Mean hospital length of stay for
      diaphragm plication was 3.7 days for video-assisted thoracoscopic diaphragm
      plication and 5.4 days for thoracotomy. After diaphragm plication, mean forced
      vital capacity, forced expiratory volume at 1 second, functional residual
      capacity, and total lung capacity improved by 17%, 21.4%, 20.3%, and 16.1%,
      respectively (p < 005) at 6 months. Mean MRC dyspnea scores also significantly
      improved in the operative cohort (p < 0001). Seventeen patients in the surgical
      cohort had returned to work at 6 months. Seven patients treated without surgery
      displayed a trend toward more frequent hospitalizations and deteriorating
      pulmonary spirometry and MRC dyspnea scores during the follow-up period.
      CONCLUSIONS: Plication of the hemidiaphragm using minimally invasive techniques
      produced significant improvements in patients' functional status, pulmonary
      spirometry, and MRC dyspnea scores. Video-assisted thoracoscopic diaphragm
      plication should be considered appropriate therapy in symptomatic adult patients
      with unilateral diaphragm paralysis.

PMID- 16631686
TI  - Long-term observation and functional state of the esophagus after primary repair
      of spontaneous esophageal rupture.
AB  - BACKGROUND: Long-term outcome of patients treated for a spontaneous esophageal
      rupture (Boerhaave's syndrome) is seldom reported. METHODS: From 1989 to 2004, 62
      esophageal perforations were treated in a single institution. Eighteen patients
      presented with a spontaneous esophageal rupture. Among them, 15 could be treated
      with a transthoracic primary repair and constituted the material of the present
      study. A chart review was performed with special attention to survival, residual
      symptoms, and anatomic and motility disorders. RESULTS: Three patients died
      postoperatively (20%). At last follow-up, 10 patients were alive and 2 had died
      from unrelated causes. At a median delay of 13 months (3 to 74), 7 patients
      accepted to undergo complementary investigations. None of them had any anatomic
      abnormality as checked by barium swallow. Six patients complained of mild
      symptoms from gastroesophageal reflux. Six patients (85%) presented with
      esophageal motility disorders on manometry and 4 (54%) had nocturne chronic
      reflux disease on pH monitoring. Two patients underwent endoscopic
      ultrasonography, of which one presented with a focal absence of one layer of the
      esophageal wall within the area of the suture. With time, no patient experienced
      recurrence, but one developed a cancer in the cervical esophagus. CONCLUSIONS:
      These results suggest that esophageal functional disorders are the rule after
      primary repair of a Boerhaave's syndrome. Whether or not these findings are
      causal, coincidental, or related to the surgical treatment remains unclear.
      However, performance of routine postoperative explorations is strongly encouraged
      for a better understanding of this challenging condition.

PMID- 16631687
TI  - Thoracoscopic sympathectomy for isolated facial blushing.
AB  - BACKGROUND: Facial blushing is one of the most peculiar of human expressions and
      has become a cardinal symptom of social phobia. The pathophysiology is unclear
      and the prevalence is unknown. Thoracoscopic sympathectomy may cure the symptom,
      but very few surgeons treat patients with isolated facial blushing. The
      literature is limited, and there are few long-term follow-up studies. METHODS: A
      follow-up study by questionnaire in 180 consecutive patients who underwent
      thoracoscopic sympathectomy for isolated facial blushing at two Danish university
      hospitals during a 6-year period. Patients routinely underwent T2 sympathectomy
      at the university hospital in Aarhus (n = 101) and T2-T3 sympathectomy at the
      university hospital in Odense (n = 79). RESULTS: The questionnaire was returned
      by 96% of the patients after a median follow-up time of 20 months. Overall, 90%
      of the patients had some effect from the operation, and the result was excellent
      or satisfactory in 75%. There was no significant difference between the two
      extents of sympathectomy. Compensatory sweating occurred in 88% of all patients
      and was significantly more frequent after T2-T3 sympathectomy (p = 0.02) Ten
      percent of our patients regretted the operation because of side effects or no
      effect of the operation. CONCLUSIONS: This study demonstrates that thoracoscopic
      sympathectomy is an effective treatment for isolated facial blushing. The
      majority of patients achieve an excellent or satisfactory long-term result. Our
      results suggest that a T2 sympathectomy is superior for patients with isolated
      facial blushing because side effects are lower compared with a T2-T3
      sympathectomy.

PMID- 16631688
TI  - A novel approach: treatment of bronchial stump fistula with a plugged, bullet
      shaped, angled stent.
AB  - PURPOSE: The purpose of this study was to evaluate the initial clinical efficacy
      of a plugged, bullet-shaped, angled stent for managing bronchial stump fistula.
      DESCRIPTION: The stent consisted of two parts. The body part had a diameter of 18
      approximately 25 mm and was 30 mm long in a tubular configuration covered with
      polyethylene at the lower part. The bronchial limb was a bullet-shaped
      configuration with a dead end, 11 approximately 14 mm in diameter, 10
      approximately 30 mm long covered with polyethylene. The body part and the
      bronchial limb were connected at the angled portion without overlap with use of
      nitinol wire and polyethylene. The stents were placed in 6 patients under
      fluoroscopic guidance. EVALUATION: Stent placement was technically successful in
      all patients without complications. Immediate closure of the bronchial stump
      fistula was achieved in all patients after stent placement. Follow-up of 4
      approximately 16 months, permanent closure of the bronchial pleural fistula was
      achieved in 4 patients (66.67%), and permanent closure of the bronchial stump
      fistula was achieved in 5 patients (83.33%). No complications occurred.
      CONCLUSIONS: Closure of the bronchial stump fistula with the stent was a simple,
      safe, and effective procedure.

PMID- 16631689
TI  - Invited commentary.

PMID- 16631690
TI  - Emergency endovascular deployment of stent graft in the ascending aorta for
      contained rupture of innominate artery pseudoaneurysm in a pediatric patient.
AB  - Endovascular approaches to treat aortic diseases have become an important
      alternative to open surgical intervention in aortic pathologies. We report a case
      of an emergency placement of a stent graft in a 16-year-old boy with a contained
      rupture of an innominate artery pseudoaneurysm. This patient had been previously
      treated for a mediastinal T-cell lymphoma and underwent mediastinal
      chemoradiation. He developed tracheal stenosis, requiring multiple tracheal
      reconstructive surgical procedures, and subsequently emergency ligation of a
      tracheal-innominate fistula. A pseudoaneurysm of the previously ligated
      innominate artery developed. Despite coil embolization, it continued to enlarge,
      requiring emergency endovascular intervention. A pseudoaneurysm of the previously
      ligated innominate artery subsequently developed, and despite coil embolization,
      it continued to enlarge, which required emergency endovascular intervention.

PMID- 16631691
TI  - Unusual case of late thoracic stent graft failure after cardioversion.
AB  - We report the unusual case of successful endovascular exclusion of a thoracic
      aortic aneurysm with subsequent thoracic aortic aneurysm reduction, and
      development of an interval, acute type III endoleak after cardioversion 5 years
      after stent graft deployment.

PMID- 16631692
TI  - Cartilaginous and osseous metaplasia with bone marrow formation in the aortic
      valve of a patient with giant cell aortitis.
AB  - We describe the case of a 40-year-old man who presented with an ascending aortic
      aneurysm and aortic valve regurgitation. The patient underwent a Bentall surgical
      procedure. Pathologic findings were consistent with giant cell aortitis with
      synchronous cartilaginous and osseous metaplasia with bone marrow formation in
      the degenerated aortic valve. The coexistence of these findings has not been
      previously reported in the English language literature.

PMID- 16631693
TI  - Fracture of Colvin-Galloway Future band causing a tear in the anterior mitral
      leaflet.
AB  - The first case of a fracture of a semi-rigid annuloplasty device is reported. A
      56-year-old man presented with recurrence of severe mitral and tricuspid
      regurgitation 10 months after proper implantation of a Colvin-Galloway Future
      band (Medtronic Inc, Minneapolis, MN). During redo surgery we made the unexpected
      finding that its metal skeleton was fractured near the posterior segment. A tear
      in the anterior mitral leaflet was also found. It is speculated that the device
      fracture may have put additional strain on the native annulus.

PMID- 16631694
TI  - Infective endocarditis and pseudoaneurysm: fatal complications of mitral annular
      calcification.
AB  - We present a case of successful surgical repair for infected mitral valve and
      left ventricular pseudoaneurysm, which can be fatal complications of mitral
      annular calcification.

PMID- 16631695
TI  - Simultaneous hybrid revascularization by carotid stenting and coronary artery
      bypass grafting.
AB  - Surgical treatment of simultaneous coronary and carotid disease is still
      controversial, because of the high risk of morbidity and mortality after combined
      or staged carotid artery endoarterectomy and the coronary artery bypass grafting
      approach. We report the first 10 patients with concomitant coronary and carotid
      disease successfully treated with an alternative strategy consisting of
      simultaneous hybrid revascularization by carotid artery stenting and coronary
      artery bypass grafting.

PMID- 16631696
TI  - Right thoracotomy for saphenous vein graft aneurysm causing hemoptysis.
AB  - Hemoptysis and septicemia 6 years after coronary artery bypass surgery in a 56
      year-old man was caused by a 5-cm vein graft pseudoaneurysm bleeding into the
      right pleura and lung parenchyma. The graft was approached through a right
      thoracotomy. The patient suffered postoperative neuromyopathy, but fully
      recovered within 6 months without muscular, respiratory, or cardiac symptoms.

PMID- 16631697
TI  - Cavo-atrial tumor resection under total circulatory arrest without a sternotomy.
AB  - Surgical management of intracardiac tumors arising in the inferior vena cava
      often requires total circulatory arrest for safe and adequate resection. Total
      circulatory arrest has traditionally been accomplished by accessing the great
      vessels through a sternotomy. Combination of a sternotomy and a large abdominal
      incision results in excellent exposure but also creates the potential for
      significant morbidity. We report here the resection of cavoatrial tumors by
      achieving total circulatory arrest through femoral arterial and venous
      cannulation without requiring a sternotomy. This minimal-access total circulatory
      approach has the potential to greatly diminish morbidity when managing tumors of
      the inferior vena cava.

PMID- 16631698
TI  - Intermediate type atrioventricular septal defect in the elderly.
AB  - A 65-year-old woman with intermediate type atrioventricular septal defect had
      been undiagnosed until initial presentation with congestive heart failure. She
      underwent surgery when the ventricular septal defect was found to be restrictive.
      The atrioventricular valve was similar to the common atrioventricular valve, but
      was connected to the crest of the ventricular septal defect. Surgery included
      direct closure of the ventricular septal defect, repair of the cleft in the
      atrioventricular valve, and ostium primum closure. Postoperative echocardiography
      indicated successful heart repair. We present a review of rare intermediate type
      atrioventricular septal defect in the elderly, and we discuss the surgical issues
      in this case.

PMID- 16631699
TI  - Heterotaxy syndrome with azygous continuation-causing pseudo Budd-Chiari syndrome
      after cardiopulmonary bypass.
AB  - Heterotaxy syndrome with interruption of the inferior vena cava and direct
      hepatic vein inflow into the right atrium has important implications for cardiac
      surgery. We report a case causing pseudo Budd-Chiari syndrome after
      cardiopulmonary bypass.

PMID- 16631700
TI  - Bronchial migration of a systemic-pulmonary shunt conduit.
AB  - Using an expanded polytetrafluoroethylene conduit, a subclavian artery-to
      pulmonary artery shunt was created in an infant with tetralogy of Fallot. The
      postoperative course was complicated by sepsis, shunt occlusion, and pneumonia.
      Four years later, an obstructive mass was found in the right main bronchus on
      fluoroscopy and was retrieved on rigid endoscopy, which turned out to be the
      migrated conduit. This case implies that a vascular conduit anastomosed to a
      systemic artery can migrate into the airway without bleeding, pseudoaneurysm
      formation, or host artery occlusion.

PMID- 16631701
TI  - Creation of coronary sinus using left atrial diaphragm in the patient with cor
      triatriatum and unroofed coronary sinus.
AB  - Surgical correction of cor triatriatum with unroofed coronary sinus consisted of
      creation of the coronary sinus using the left atrial diaphragm and closure of the
      atrial septal defect in an adult patient. No materials other than intracardiac
      components were used to repair all anomalies.

PMID- 16631702
TI  - Chronic heart perforation with 13.5 cm long Kirschner wire without pericardial
      tamponade: an unusual sequelae after shoulder fracture.
AB  - We report a unique case of cardiac embolization with the Kirschner wire that has
      been used for osteosynthesis for 24 months previously. According to the complete
      analysis of medical records and autopsy report, the wire had migrated from the
      right humeroscapular joint to the heart. Although migration of a Kirschner wire
      has been reported in the literature, migration of the wire with a total length of
      13.5 cm with no pericardial tamponade, despite myocardial perforation, has not
      been previously described.

PMID- 16631703
TI  - Pulmonary artery leiomyosarcoma expressing Epstein-Barr virus in an
      immunocompetent individual.
AB  - Primary leiomyosarcoma of the pulmonary artery is extremely uncommon and its
      cause remains unclear. We document a case of pulmonary artery leiomyosarcoma
      expressing Epstein-Barr virus DNA sequences in an immunocompetent patient 4 years
      after symptomatic Epstein-Barr virus infection.

PMID- 16631704
TI  - Thoracoscopic repair of tracheoesophageal fistula in a septuagenarian.
AB  - We report the case of a 79-year-old female with clinical and radiographic
      evidence of congenital H-type tracheoesophageal fistula. Past medical history
      included recurrent pneumonia and episodic cough with food or fluid intake. She
      exhibited Ohno's sign during the dysphagia evaluation. A video swallow study
      demonstrated evidence of aspiration. Esophagogram and bronchoscopy identified the
      fistulous tract. Repair of the anomaly was performed using a minimally invasive
      thoracoscopic approach. In our experience, excellent visualization and
      magnification of the anatomic field with use of thoracoscopy allowed for relative
      ease of dissection and resection of the tract with minimal postoperative
      morbidity.

PMID- 16631705
TI  - Intercostal neuralgia caused by a parosteal lipoma of the rib.
AB  - Parosteal lipoma is an extremely rare benign tumor that is composed mainly of
      mature adipose tissue, and it has an intimate relationship to the underlying
      periosteal bone. We believe that only three cases have been previously reported
      that have described parosteal lipoma of the rib. Although parosteal lipoma is
      asymptomatic, motor and sensory function deficits have been reported that were
      caused by the tumor compressing the neuromuscular bundles in the proximal forearm
      and the sciatic nerve. We present here an exceedingly rare case of intercostal
      neuralgia caused by a parosteal lipoma of the rib.

PMID- 16631706
TI  - Meningioma of the mediastinum causing spontaneous hemothorax.
AB  - Ectopic meningiomas are extremely rare. Mediastinal tumors may rarely cause
      spontaneous hemothorax. We report a case of angioblastic meningioma of the
      posterior mediastinum causing spontaneous hemothorax.

PMID- 16631707
TI  - Anterior mediastinal mass in a patient with Graves' disease.
AB  - Thymic hyperplasia is a common feature in Graves' disease. However, in most
      cases, thymic enlargement is minimal, and radiologically detectable massive
      enlargement of the thymus is infrequently reported. Half of them undergo
      thymectomy due to the concern about a thymoma. We report a 28-year-old woman with
      untreated Graves' disease. She had an anterior mediastinal mass that was
      diagnosed as true thymic hyperplasia by biopsy and disappeared after treatment of
      the hyperthyroid state. Recognizing the association between thymic hyperplasia
      and Graves'disease, and existence of the benign course after treatment of the
      hyperthyroidism may be useful for avoiding unnecessary surgical procedure.

PMID- 16631708
TI  - Images in cardiothoracic surgery. Superior vena cava filter erosion into the
      ascending aorta.

PMID- 16631709
TI  - Images in cardiothoracic surgery. Persistent fifth aortic arch.

PMID- 16631710
TI  - Longitudinal plication of the posterior leaflet in myxomatous disease of the
      mitral valve.
AB  - In selected cases, resection of a prolapsing scallop of the posterior leaflet
      (generally P2) is not advisable because of the excessive length of insertion of
      the scallop. In such cases, insertion of artificial chordae is advisable, but the
      height of the scallop needs to be reduced. We used longitudinal plication of the
      scallop(s) in which the height was excessive with "U" sutures in 11 consecutive
      patients. Early and intermediate echocardiographic results were fully satisfying,
      and we expect that the morphologic aspect of the repaired mitral valve will
      remain stable after a longer follow-up.

PMID- 16631711
TI  - The blower: a useful tool to complete thrombectomy of the mechanical prosthetic
      valve.
AB  - Thrombectomy could be an excellent approach on one condition (ie, that all parts
      of the thrombus are removed). We propose to use a tool (ie, the blower) to
      complete thrombectomy of the prosthetic mechanical valve. The blower is a
      vaporizer that mixes air and heparinized saline with regulator of flow and
      proportion used in beating heart surgery. For thrombectomy, we have modified the
      air-water mixing part and intensity until we obtained a jet that enabled us to
      remove the micro thrombus that covered the prosthetic valve and surrounding
      tissues. The blower completely cleaned the prosthetic valve. With this tool,
      thrombectomy seems easier, more complete, and more reliable with the advantages
      of short cross-clamping time.

PMID- 16631712
TI  - Combined severe pectus excavatum correction and aortic root replacement in
      Marfan's syndrome.
AB  - A 23-year-old man with Marfan's syndrome was admitted for repair of annulo-aortic
      ectasia and severe pectus excavatum. A submammary skin incision approach followed
      by bilateral subperichondrial resection of abnormal costal cartilages was
      performed. The left intercostal muscles and perichondrial sheaths were divided 2
      inches lateral to the sternum in a parasternal fashion to place the retractor.
      The aortic root was replaced with a 23-mm St. Jude's composite graft (St. Jude
      Medical, Inc, St. Paul, MN). Chest wall reconstruction was completed with a high
      sternal osteotomy and support of the sternum was made with Gortex strips (W.L.
      Gore & Associates, Inc, Flagstaff, AZ). The patient made an uneventful recovery.

PMID- 16631713
TI  - Aortic cannulation through the aneurysm for repair of thoracoabdominal aortic
      aneurysms.
AB  - We hereby present our experiences with arterial cannulation through the aneurysm
      in patients with thoracoabdominal aortic aneurysm. This can be a good option for
      thoracoabdominal aortic aneurysm repair in patients with diseased peripheral
      arteries.

PMID- 16631714
TI  - Coronary stenting and inflammation: implications for further surgical and medical
      treatment.
AB  - The introduction of percutaneous coronary interventions (PCI) with stent implant
      has substantially shifted the treatment of coronary artery disease. The current
      approach to coronary artery disease treatment includes first-choice PCI in
      selected subgroups; and once this therapy fails, frequently the patient is
      referred for coronary artery bypass graft surgery. However, evidence of chronic
      inflammatory reaction and endothelial dysfunction after PCI has been emerging and
      that might be interfering with patient outcome when surgical or medical
      treatments are subsequently required. The clinical significance of these
      complications after PCI, herein examined, has been less studied and needs better
      assessment. Also, the premise that coronary artery bypass graft surgery can
      safely be performed in patients with coronary stenting failure may not hold true,
      as graft patency might be adversely affected. Furthermore, the superimposed
      inflammatory reaction may blunt the efficacy of medical treatment.

PMID- 16631715
TI  - Postoperative chemotherapy in nonsmall cell lung cancer: a systematic review.
AB  - A systematic review of the evidence for postoperative chemotherapy in completely
      resected nonsmall cell lung cancer was conducted. Seven meta-analyses and 25
      randomized trials met the pre-defined eligibility criteria for the review. The
      evidence indicates that postoperative platinum-based chemotherapy improves
      survival compared with surgery alone; for patients with a good performance status
      who are fit enough for chemotherapy, the survival benefits strongly outweigh the
      adverse effects of treatment. To date the trials restricted to stage IB or II
      disease have obtained the greatest survival benefits with postoperative platinum
      based chemotherapy. The evidence does not support the use of postoperative
      radiotherapy with chemotherapy.

PMID- 16631716
TI  - What is operative mortality? Defining death in a surgical registry database: a
      report of the STS Congenital Database Taskforce and the Joint EACTS-STS
      Congenital Database Committee.
AB  - The most concrete and universal outcome measure used in databases, whether
      governmental, professional society, research, or third-party payer, is operative
      mortality. To assure congruous data entry by multiple users of The Society of
      Thoracic Surgeons and the European Association for Cardiothoracic Surgery
      congenital heart surgery databases, operative mortality must be clearly defined.
      Traditionally, operative mortality has been defined as any death, regardless of
      cause, occurring (1) within 30 days after surgery in or out of the hospital, and
      (2) after 30 days during the same hospitalization subsequent to the operation.
      Differing hospital practices result in problems in use of the latter part of the
      definition (eg, the pediatric hospital that provides longer-term care will have
      higher mortality rates than one which transfers patients to another institution
      for such care). In addition, because of the significant number of pediatric
      multiple operation hospitalizations, issues of assignment of mortality to a
      specific operation within the hospitalization, calculation of operative mortality
      rates (operation based vs patient admission based), and discharge other than to
      home must be addressed and defined. We propose refinements to the definition of
      operative mortality which specifically meet the needs of our professional
      societies' multi-institutional registry databases, and at the same time are
      relevant and appropriate with respect to the goals and purposes of administrative
      databases, government agencies, and the general public.

PMID- 16631718
TI  - Seeding human endothelial cells on complex three-dimensional scaffolds.

PMID- 16631720
TI  - Extracranial carotid aneurysms in young patients.

PMID- 16631722
TI  - Temporal aspects of anti-heparin-PF4 antibodies in heparin-induced
      thrombocytopenia.

PMID- 16631724
TI  - Papaverine dissection for harvesting internal mammary artery.

PMID- 16631725
TI  - Preoperative use of steroids in patients with myasthenia gravis.

PMID- 16631727
TI  - Mediastinal lymph node metastases and visceral pleural invasion in nonsmall cell
      lung cancer patients.

PMID- 16631729
TI  - Temporal regulation of late expression of Bar homeobox genes during Drosophila
      leg development by Spineless, a homolog of the mammalian dioxin receptor.
AB  - The spatial and temporal regulation of genes encoding transcription factors is
      essential for the proper development of multicellular organisms. In Drosophila
      leg development, the distal-most tarsus (ta5) is specified by the strong
      expression of a pair of Bar homeobox genes in late third instar. This expression
      is regulated under the control of the ta5 enhancer activated by Bar. No
      activation of the ta5 enhancer, however, occurs in early third instar when
      considerable Bar is produced. The ta5 enhancer was comprised of a basal enhancer
      required for driving Bar expression and a negative regulatory motif serving as a
      binding site for the heterodimer of Spineless and Tango, homologs of the
      mammalian dioxin receptor and aryl hydrocarbon nuclear translocator,
      respectively. The spineless and tango were essential for suppressing the basal
      enhancer activation in early third instar. The spineless was transiently
      expressed in early third instar in the Bar expression domain. ta5 Bar expression
      may thus be temporally regulated through transient inhibition of premature
      activation of the basal enhancer via specific binding of the Spineless/Tango
      heterodimer to the negative regulatory motif in early third instar and subsequent
      release from the inhibition due to the disappearance of spineless expression at
      later stages.

PMID- 16631730
TI  - An orally active reversible inhibitor of cathepsin S inhibits human trans vivo
      delayed-type hypersensitivity.
AB  - Cathepsin S is a major histocompatibility complex (MHC) class II associated
      invariant chain (Ii) degrading enzyme expressed in antigen presenting cells such
      as B cells and dendritic cells. This enzyme is essential for MHC class II
      associated antigen processing and presentation to CD4(+) T cells. Compound I, a
      selective, reversible and orally bioavailable, inhibitor of cathepsin S, with
      molecular IC(50)=9 nM, has been recently described. We have tested the effects of
      compound I in a trans vivo model of delayed-type hypersensitivity. Human
      peripheral blood mononuclear cells (7-10 x 10(6)) from tetanus-sensitized donors
      were co-injected with tetanus toxoid (0.25 Lf) into C57Bl/6 mouse footpads. At 24
      h, significant footpad swelling (+0.024+/-0.001 cm) characterized by an influx of
      mouse neutrophils and monocytes was observed. Injection of peripheral blood
      mononuclear cells alone caused negligible swelling (0.002+/-0.0002 cm). Anti
      human MHC class II (HLA-DR, DP, DQ) antibody (5 mg/kg, i.p.) inhibited the
      swelling 91+/-7%, thus demonstrating a role of human antigen presenting cells in
      this model. Compound I (10, 30, and 100 mg/kg, p.o.) inhibited the response with
      an ED50 of approximately 18 mg/kg. Compound III, a less active analogue
      (molecular IC50>20 microM) had no effect. Furthermore, pretreatment of peripheral
      blood mononuclear cells with 10 nM compound II, an irreversible inhibitor
      (molecular IC50=11 nM) inhibited swelling 87+/-4%. These findings support the
      role of cathepsin S in human delayed-type hypersensitivity. Inhibition of
      cathepsin S with compound I may be useful in the treatment of human autoimmune
      diseases like rheumatoid arthritis and multiple sclerosis.

PMID- 16631731
TI  - The contractile effect of the ghrelin receptor antagonist, D-Lys3-GHRP-6, in rat
      fundic strips is mediated through 5-HT receptors.
AB  - Ghrelin is an orexigenic peptide present in the stomach with gastroprokinetic
      properties. Previous in vivo studies have shown that the ghrelin receptor
      antagonist, D-Lys(3)-GHRP-6, reduced food intake and delayed gastric emptying in
      rodents but these effects are at variance with the normal phenotype of the
      ghrelin knockout mice. To verify the specificity of the effects observed with D
      Lys(3)-GHRP-6 this study aimed to investigate the pharmacology of D-Lys(3)-GHRP-6
      in vitro. Rat fundic strips were suspended in a tissue bath and the contraction
      of strips to 10(-5) M of ghrelin, GHRP-6 or D-Lys(3)-GHRP-6 was measured
      isometrically in the absence and presence of blockers. Neither ghrelin, nor GHRP
      6, induced significant contractions in the absence of electrical field
      stimulation thereby excluding the presence of ghrelin receptors on smooth muscle
      cells. In contrast D-Lys(3)-GHRP-6, induced a pronounced biphasic contraction of
      13.9+/-1.8% and 40.5+/-3.2% relative to the response to 60 mM KCl. The
      contraction was blocked by the 5-HT(1,2) receptor antagonist methysergide and was
      markedly reduced by the 5-HT(2B) receptor antagonist, yohimbine, which also
      profoundly affected 5-HT induced contractions in fundic strips. The existence of
      5-HT(2B) receptors in the fundus was confirmed by use of the 5-HT(2B) receptor
      agonist, BW 723C86. In contrast to ghrelin and GHRP-6, the ghrelin receptor
      antagonist, D-Lys(3)-GHRP-6, induced pronounced smooth muscle contractions in the
      rat fundus by interacting with 5-HT(2B) receptors. This may question the role of
      endogenous ghrelin in the effects observed with D-Lys(3)-GHRP-6 on food intake
      and gastric emptying in vivo.

PMID- 16631732
TI  - T-cadinol and calamenene induce dendritic cells from human monocytes and drive
      Th1 polarization.
AB  - T-cadinol and calamenene are sesquiterpenes isolated from the heartwood of
      Cryptomeria japonica and are pharmacologically active substances. Dendritic cells
      are pivotal in the initiation of adaptive immune responses and are recognized as
      key to the induction of immune responses to cancer. This study investigated the
      effects of T-cadinol and calamenene on the phenotypic and functional maturation
      of human monocyte-derived dendritic cells in vitro. Human monocytes were cultured
      with recombinant human granulocyte-macrophage colony-stimulation factor (GM-CSF)
      and recombinant human interleukin-4 (IL-4) for 6 days under standard conditions,
      followed by another 2 days in the presence of T-cadinol, calamenene,
      lipopolysaccharide (LPS), CT or nifedipine. Dendritic cells harvested on day 8
      were examined using functional assays. The expression levels of CD1a, CD80, CD83,
      CD86 and HLA-DR on T-cadinol-primed dendritic cells or calamenene-primed
      dendritic cells were enhanced with a concomitant decrease in endocytic activity.
      T-cadinol-primed dendritic cells or calamenene-primed dendritic cells also
      enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte
      reaction, as measured by T cell proliferation. Naive T cells co-cultured with
      allogeneic T-cadinol-primed dendritic cells or calamenene-primed dendritic cells
      at 1:5 dendritic cells/T cell ratio turned into typical Th1 cells which produced
      large quantities of interferon-gamma (IFN-gamma) and released small amounts of IL
      4 depending on IL-12 secretion. In contrast, naive T cells co-cultured with CT
      primed dendritic cells turned into Th2 cells. T-cadinol-primed dendritic cells
      and calamenene-primed dendritic cells expressed the chemokine receptor CCR7 and
      had a high migration to macrophage inflammatory protein (MIP-3beta).
      Intracellular Ca(2+) mobilization in T-cadinol-primed dendritic cells and
      calamenene-primed dendritic cells was induced by MIP-3beta. The differentiation
      and functional maturation of human monocyte-derived dendritic cells were not
      affected by nifedipine. These results suggest that T-cadinol and calamenene may
      be used in dendritic cells-based immunotherapy for cancer.

PMID- 16631733
TI  - High glucose enhances inducible nitric oxide synthase expression. Role of protein
      kinase C-betaII.
AB  - The aim was to determine whether high glucose levels interfere with nitric oxide
      (NO) production and inducible NO synthase (iNOS) protein expression in
      interleukin-1beta-stimulated vascular smooth muscle cells from normotensive
      Wistar Kyoto and spontaneously hypertensive rats. Cells were incubated with
      either normal (5.5 mM) or high (22 mM) d-glucose for 72 h and with interleukin
      1beta (10 ng/ml) for the last 24 h. High glucose increased nitrite levels, iNOS
      expression and protein kinase C activity in cells from normotensive rats and had
      no effect in cells from hypertensive rats. High glucose effects on nitrite
      production and iNOS expression was abolished by the selective inhibitor for the
      protein kinase C-betaII, 5,21:12,17-dimetheno-18H-dibenzo[i,o]pyrrolo[3,4-1]
      [1,8]diacyclohexadecine-18,20 (19H)-dione, 8-[(dimethylamino) methyl]
      6,7,8,9,10,11-hexahydro-monomethanesulfonate (LY379196, 30 nM). Calphostin C (1
      microM) and LY379196 (10 microM) reduced nitrite levels and iNOS expression only
      in cells from normotensive rats treated with both media. These results suggest
      that high glucose increases inducible nitric oxide synthase induction and
      subsequent NO production by activating the protein kinase C-betaII; this
      mechanism seems to be altered in hypertension.

PMID- 16631734
TI  - Neuroprotective activity of honokiol and magnolol in cerebellar granule cell
      damage.
AB  - The aim of the present study was to investigate the neuroprotective effects of
      honokiol and magnolol, two major bioactive constituents of the bark of Magnolia
      officinalis, against neuron toxicity induced by glucose deprivation, excitatory
      amino acids and hydrogen peroxide (H(2)O(2)) in cultured rat cerebellar granule
      cells. Cell membrane damage was measured with a lactate dehydrogenase (LDH)
      release assay and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide
      (MTT) assay was used to assess mitochondrial activity, reflecting cell survival.
      Results showed that honokiol and magnolol alone did not affect mitochondrial
      function and cell damage, but significantly reversed glucose deprivation-induced
      mitochondrial dysfunction and cell damage. The glutamate receptor blocker MK-801
      and antioxidant vitamin E also provided protection against this damage.
      Furthermore, honokiol was more potent than magnolol in protecting against
      glutamate-, N-methyl-D-aspartate (NMDA)- and H(2)O(2)-induced mitochondrial
      dysfunction. These results demonstrated that the neuroprotective effects of
      honokiol and magnolol may be related to their anti-oxidative actions and
      antagonism of excitotoxicity induced by excitatory amino acids, suggesting that
      both compounds may be potential therapeutic agents for neurodegenerative
      diseases.

PMID- 16631735
TI  - The in vivo effects of human urotensin II in the rabbit and rat pulmonary
      circulation: effects of experimental pulmonary hypertension.
AB  - In vivo haemodynamic responses to human urotensin-II were determined in two
      models of pulmonary hypertension: rabbits with left ventricular dysfunction
      following coronary artery ligation and the hypoxic rat. Effects were also
      examined in the presence of the nitric oxide synthase inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME). Human urotensin-II increased pulmonary arterial
      pressure to a greater extent in ligated rabbits than their controls and L-NAME
      increased pulmonary pressure without significantly affecting these responses to
      human urotensin-II. Human urotensin-II raised right ventricular pressure slightly
      in control rats but not in hypoxic rats. Human urotensin-II did not constrict
      control rat isolated small pulmonary arteries and only induced a small
      constriction of these vessels in hypoxic rats. In conclusion, exogenous human
      urotensin-II exerts pulmonary pressor responses in vivo in rabbits and also
      induced small pulmonary pressor responses in control rats. Pulmonary pressor
      responses to urotensin-II were increased by pulmonary hypertension in rabbits but
      not in rats.

PMID- 16631736
TI  - TNF-receptor I defective in internalization allows for cell death through
      activation of neutral sphingomyelinase.
AB  - The cytoplasmic tail of the tumor necrosis factor receptor I (TNF-RI) contains
      several functionally distinct domains involved in apoptotic signaling. Mutants of
      TNF-RI carrying deletions of the death domain (DD), internalization domain
      (TRID), and neutral sphingomyelinase domain (NSD), respectively, retransfected in
      cells devoid of TNF-RI and TNF-RII, constituted distinct tools to evaluate the
      specific role of each domain in downstream apoptotic signaling events. Deletion
      of DD abolishes activation of caspase-3 and -9 and apoptosis following treatment
      with TNF because of blocked assembly of the DISC. Nevertheless, TNF-RI DeltaTRID,
      though lacking a DISC, still allows for residual activation of caspase-3 followed
      by cell death, although caspase-9 activation was not detected. This activity of
      caspase-3 is probably due to activation of neutral sphingomyelinase (N-SMase).
      Increased activity of this enzyme was detected in cells expressing TNF-RI
      DeltaTRID following treatment with TNF, but not in any other cell line
      investigated. N-SMase is activated by factor associated with N-SMase (FAN).
      Because TNF-RI DeltaTRID is retained at the cell surface, FAN may interact with
      the mutated receptor for a prolonged amount of time, thereby overactivating N
      SMase. Double deletion of TRID and NSD abolished caspase-3 activation and
      apoptosis, confirming this hypothesis.

PMID- 16631737
TI  - Immune modulation by mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have been shown to suppress activation of T cells
      both in vivo and in vitro. In vivo, this may be a way for the body to maintain
      homeostasis and inhibit immune activation in distinct compartments, such as the
      bone marrow and the interface between mother and fetus. MSCs modulate the immune
      function of the major cell populations involved in alloantigen recognition and
      elimination, including antigen presenting cells, T cells, and natural killer
      cells. The molecular mechanism that mediates the immunosuppressive effect of MSCs
      is not completely understood.

PMID- 16631738
TI  - Bach2 is involved in neuronal differentiation of N1E-115 neuroblastoma cells.
AB  - Bach1 and Bach2 are evolutionarily related members of the BTB-basic region
      leucine zipper transcription factor family. We found that Bach2 downregulates
      cell proliferation of N1E-115 cells and negatively affects their potential to
      differentiate. Nuclear localization of the cyclin-dependent kinase inhibitor p21
      is known to arrest cell cycle progression, and cytoplasmic p21 has been shown to
      promote neuronal differentiation of N1E-115 cells. We found that ectopic Bach2
      causes upregulation of p21 expression in the nucleus and in the cytoplasm in
      undifferentiated N1E-115 cells. In differentiated cells, Bach2 specifically
      triggers upregulation of cytoplasmic p21. Our data suggest that Bach2 expression
      could represent a switch during the process of neuronal differentiation. Bach2 is
      not expressed in neuronal precursor cells. It would have negative effects on
      proliferation and differentiation of these cells. In differentiated neuronal
      cells Bach2 expression is upregulated, which could allow Bach2 to function as a
      gatekeeper of the differentiated status.

PMID- 16631739
TI  - Synchronous modulation of cell surface lectin and its receptor in a homologous
      cell population: a novel mechanism of cellular regulation.
AB  - Testicular immotile sperm undergo maturation during epididymal transit when these
      cells pass through caput, corpus, and cauda-epididymal regions. Maturing goat
      spermatozoa specifically at the distal corpus epididymal stage show head-to-head
      autoagglutination when incubated in vitro in a modified Ringer's solution. Here,
      we show the biochemical mechanism of autoagglutination event and its functional
      significance. A lectin-like molecule located on sperm surface specifically
      interacts with its receptor of the neighboring homologous cells to cause
      autoagglutination. Lectin is a Ca++-dependent galactose-specific protein. Failure
      of the pre- and post-distal corpus sperm to show autoagglutination is due to lack
      of lectin-like molecule and its receptors, respectively. Maturing sperm at distal
      corpus stage acquire lectin-like molecule followed by sharp disappearance of its
      receptor, and this event is synchronously associated with the initiation of sperm
      forward motility that is essential for fertilization in vivo. Lectin and its
      receptor isolated from sperm plasma membrane showed high efficacy for blocking
      autoagglutination phenomenon. The data are consistent with the view that
      synchronous modulation of homologous cell surface lectin and their receptors
      constitutes a novel mechanism for cellular regulation by generating waves of
      signals by manipulating lectin-sugar-dependent "self-talk" and cell-cell "cross
      talk".

PMID- 16631740
TI  - Alpha-V-dependent outside-in signaling is required for the regulation of CD44
      surface expression, MMP-2 secretion, and cell migration by osteopontin in human
      melanoma cells.
AB  - The level of integrin alpha(v)beta3 and its ligand osteopontin (OPN) has been
      directly correlated to tumorigenicity of melanoma and other cancer cells. We have
      previously shown an increase in pp(60c-Src) kinase activity associated with
      integrin alpha(v)beta3 in melanoma cells (M21) treated with soluble OPN. pp(60c
      Src) kinase activity was not observed in melanoma cells expressing alpha(v) that
      lacks the cytoplasmic domain (alpha(v)995). Results of the current study
      demonstrate that the amino acid sequence '995RPPQEEQERE1004' in the beta-turn of
      alpha(v) chain is required for the interaction of pp(60c-Src). Our results
      suggest that the beta-turn of alpha(v) chain may be indispensable for alpha(v)
      associated signaling complex formation and outside-in signaling. To further
      analyze the alpha(v)beta3 signaling in melanoma cells, we over expressed OPN in
      M21 cells (M21/OPN). CD44 surface expression and MMP-2 activity in the
      conditioned medium were increased to a greater extent in M21/OPN cells as
      compared with M21 or alpha(v)995 cells. Also, M21/OPN cells exhibit increased
      motility, which is markedly reduced upon treatment with inhibitors to alpha(v)
      and MMP-2. Our findings suggest that the increase in MMP-2 activity is integrin
      dependent as MMP-2 activity is reduced in cells treated with an inhibitor to
      alpha(v) or in alpha(v)995 cells expressing mutant alpha(v).

PMID- 16631741
TI  - Unusual splicing events result in distinct Xin isoforms that associate
      differentially with filamin c and Mena/VASP.
AB  - Filamin c is the predominantly expressed filamin isoform in striated muscles. It
      is localized in myofibrillar Z-discs, where it binds FATZ and myotilin, and in
      myotendinous junctions and intercalated discs. Here, we identify Xin, the protein
      encoded by the human gene 'cardiomyopathy associated 1' (CMYA1) as filamin c
      binding partner at these specialized structures where the ends of myofibrils are
      attached to the sarcolemma. Xin directly binds the EVH1 domain proteins Mena and
      VASP. In the adult heart, Xin and Mena/VASP colocalize with filamin c in
      intercalated discs. In cultured cardiomyocytes, the proteins also localize in the
      nonstriated part of myofibrils, where sarcomeres are assembled and an extensive
      reorganization of the actin cytoskeleton occurs. Unusual intraexonic splicing
      events result in the existence of three Xin isoforms that associate
      differentially with its ligands. The identification of the complex filamin c-Xin
      Mena/VASP provides a first glance on the role of Xin in the molecular mechanisms
      involved in developmental and adaptive remodeling of the actin cytoskeleton
      during cardiac morphogenesis and sarcomere assembly.

PMID- 16631742
TI  - Paradoxical aggregation versus oligomerisation properties of mutant and wild-type
      huntingtin fragments.

PMID- 16631743
TI  - Influence of age on stroke and preconditioning-induced ischemic tolerance in the
      brain.
AB  - Ischemic brain damage occurs through all age subgroups, ranging from the newborn
      to the elderly, but with predominance in more aged brains either in animals or in
      humans. The present understanding of the pathophysiological mechanisms of
      ischemic brain damage suggests that, despite different age and its consecutive
      changed molecular behavior to ischemic states, there is a common underlying
      cascade of events. But, there exists an age-dependent influence on stroke of
      which the few existing experimental data are complex: the immature brain is, in
      fact, less resistant to hypoxic-ischemic brain damage than its adult counterpart.
      The intermediate age subgroup is more tolerant to hypoxic-ischemic brain damage
      than either very young or more mature ages. In addition, the neuroprotective
      mechanism of ischemic preconditioning is also influenced by this different
      molecular behavior to cerebral ischemia within the different age subgroups. The
      authors put these findings from experimental or clinical studies into the context
      of the current knowledge of ischemic preconditioning of the brain and discuss
      their relevance for experimental and clinical research. From the present data, it
      seems that neuroprotection of preconditioned brain in different age subgroup is
      not the result of any difference in the extent of the underlying cascade of
      ischemic events but rather the result of different sensitivity to ischemic
      preconditioning in different age subgroups.

PMID- 16631744
TI  - Pharmacologic management of ischemic stroke: relevance to stem cell therapy.
AB  - Pharmacologic management of the acute phase of the ischemic stroke includes
      treating the physical and medical conditions that can worsen cerebral injury;
      administering intravenous thrombolytic therapy (recombinant tissue plasminogen
      activator) in those who meet current guidelines; instituting prophylactic
      measures to prevent medical complications; and initiating passive rehabilitation
      measures. New approaches under investigation include intra-arterial thrombolytic
      therapy; endovascular embolectomy and clot disruption; and neuroprotective
      treatments to preserve surviving ischemic tissue. One neuroprotective agent given
      within 6 h after stroke onset, NXY059, recently met the primary outcome measure
      in a phase III clinical trial. Pharmacologic management of the subacute and
      chronic phases involves treatment of risk factors for recurrent stroke and other
      forms of cardiovascular disease, including hypercholesterolemia, hypertension,
      and diabetes mellitus. In this phase, antiplatelet therapy can be initiated or
      continued; smoking, obesity and alcohol intake can be managed; and active
      rehabilitation can begin through physical, occupational, and speech therapy. A
      few medications to augment rehabilitation have shown promising results in small
      clinical trials, but none have been tested in large phase III trials or approved
      by the US or European regulatory agencies. Thus, there are no pharmacologic
      measures available to enhance central nervous system restorative processes after
      acute stroke, and implantation of stem cells provides one promising approach, not
      only for cell replacement but also for the provision of therapeutic molecules.

PMID- 16631745
TI  - Entamoeba histolytica: ultrastructure of the chromosomes and the mitotic spindle.
AB  - We have analyzed by transmission electron microscopy the mitotic process of
      Entamoeba histolytica trophozoites in an asynchronous population of axenically
      cultured parasites. Our observations showed that nuclear microtubules, initially
      located at random in the karyosome during prophase, formed in subsequent stages a
      mitotic spindle closely related to the nuclear membrane at the polar regions of
      dividing nuclei. In late prophase and in anaphase, chromosomes appeared as dense
      bodies 0.1-0.5 microm. At least 15 chromosomes appeared in favorable planes of
      section, arranged as an incomplete elliptical circle, in close contact with
      microtubules. There was no morphological evidence of structures resembling the
      kinetochores of higher eukaryotes. When cut in cross-section, the mitotic spindle
      was made of 28-35 microtubular rosette assemblies. The latter probably correspond
      to a similar number of chromosomes, as has been shown by others with pulse-field
      electrophoresis and fluorescence microscopy of trophozoite spreads. In turn, each
      microtubular rosette was constituted by 7-12 parallel microtubules. In later
      stages of the metaphase, two sets of chromosomes were disposed forming a pair of
      elliptical circles. An additional finding in the dividing nuclei of E.
      histolytica trophozoites was the presence of compact conglomerates of numerous
      particles 50 nm in diameter, of similar electron density, shape, and size,
      probably corresponding to RNA episomes.

PMID- 16631746
TI  - Transcriptomics tool for the human Schistosoma blood flukes using microarray gene
      expression profiling.
AB  - We report the design, fabrication, and validation of a microarray covering the
      majority of the Schistosoma japonicum and Schistosoma mansoni transcriptomes. The
      oligonucleotide microarray contains 12,166 S. mansoni and 7055 S. japonicum
      target sequences. A confidence threshold of <or=0.001 (P value) was used in all
      analyses. The cross hybridization potential of the microarray was representative
      of 10,362 probes detected in both channels, while 12,052 probes hybridised to S.
      japonicum and 11,254 probes hybridised to S. mansoni. Differential hybridisation
      consisted of 3422 probes to S. mansoni mRNA and 3103 probes to S. japonicum mRNA.
      Important biological functions, such as transport, metabolism, immune evasion and
      host-parasite immunological interplay, cell communication, and sexual maturation
      are represented on this microarray. This is the first microarray commercially
      manufactured for studying schistosomes, and the large size and verified quality
      of the resource demonstrate its power for characterising the schistosome
      transcriptome.

PMID- 16631747
TI  - Acanthamoeba castellanii: structural basis of the cytopathic mechanisms.
AB  - In this study we report observations on the structural mechanisms of the
      cytopathic effect of Acanthamoeba castellanii trophozoites on cultured MDCK cell
      monolayers. Co-incubations were carried out for a maximum of 24h. The first
      evidence of damage to the cell monolayer was detected by measuring the
      transepithelial resistance of cell monolayers that interacted with the amoebae.
      At 6h, transepithelial resistance diminished to 51% and amoebae required 5-6h to
      produce evidence of structural injury at the light microscopy level. Following
      12h of incubation, the cell monolayer was severely damaged. After making intimate
      contact with the surface of target cells, trophozoites detached cells from the
      substrate, lysed and by means of food-cups ingested the damaged cells. There was
      no morphological evidence of modifications in MDCK cell membranes, membrane
      fusion or junction formation between the amoeba and host plasma membrane. The
      lytic capacity of the amoebas appears to be the result of cytotoxic factors
      secreted by the amoebae since, when monolayers were incubated with conditioned
      medium, there was also a decrease in the transepithelial resistance. Besides,
      mechanical injury produced by the attachment and movement of the trophozoites may
      contribute to the disruption of the cell monolayer. As in other pathogenic
      amoebae, the cytopathic action of A. castellanii on the cell monolayers can
      subjectively be separated into four stages: adhesion, cytolysis, phagocytosis,
      and intracellular degradation.

PMID- 16631748
TI  - Cyclic nucleotide-gated ion channels in sensory transduction.
AB  - Cyclic nucleotide-gated (CNG) channels, directly activated by the binding of
      cyclic nucleotides, were first discovered in retinal rods, cones and olfactory
      sensory neurons. In the visual and olfactory systems, CNG channels mediate
      sensory transduction by conducting cationic currents carried primarily by sodium
      and calcium ions. In olfactory transduction, calcium in combination with
      calmodulin exerts a negative feedback on CNG channels that is the main molecular
      mechanism responsible for fast adaptation in olfactory sensory neurons. Six
      mammalian CNG channel genes are known and some human visual disorders are caused
      by mutations in retinal rod or cone CNG genes.

PMID- 16631749
TI  - Fumagillin suppresses HIV-1 infection of macrophages through the inhibition of
      Vpr activity.
AB  - HIV-1 viral protein R (Vpr) is one of the human immunodeficiency virus type 1
      encoded proteins that have important roles in viral pathogenesis. However, no
      clinical drug for AIDS therapy that targets Vpr has been developed. Here, we have
      established a screening system to isolate Vpr inhibitors using budding yeast
      cells. We purified a Vpr inhibitory compound from fungal metabolites and
      identified it as fumagillin, a chemical already known to be a potent inhibitor of
      angiogenesis. Fumagillin not only reversed the growth inhibitory activity of Vpr
      in yeast and human cells, but also inhibited Vpr-dependent viral gene expression
      upon the infection of human macrophages.

PMID- 16631750
TI  - Comparative analysis of iron regulated genes in mycobacteria.
AB  - Iron dependent regulator, IdeR, regulates the expression of genes in response to
      intracellular iron levels in M. tuberculosis. Orthologs of IdeR are present in
      all the sequenced genomes of mycobacteria. We have used a computational approach
      to identify conserved IdeR regulated genes across the mycobacteria and the genes
      that are specific to each of the mycobacteria. Novel iron regulated genes that
      code for a predicted 4-hydroxy benzoyl coA hydrolase (Rv1847) and a protease
      dependent antibiotic regulatory system (Rv1846c, Rv0185c) are conserved across
      the mycobacteria. Although Mycobacterium natural-resistance-associated macrophage
      protein (Mramp) is present in all mycobacteria, it is, as predicted, an iron
      regulated gene in only one species, M. avium subsp. paratuberculosis. We also
      observed an additional iron-regulated exochelin biosynthetic operon, which is
      present only in non-pathogenic Mycobacterium, M. smegmatis.

PMID- 16631751
TI  - Structural elements to convert Escherichia coli alpha-xylosidase (YicI) into
      alpha-glucosidase.
AB  - Escherichia coli YicI, a member of glycoside hydrolase family (GH) 31, is an
      alpha-xylosidase, although its amino-acid sequence displays approximately 30%
      identity with alpha-glucosidases. By comparing the amino-acid sequence of GH 31
      enzymes and through structural comparison of the (beta/alpha)(8) barrels of GH 27
      and GH 31 enzymes, the amino acids Phe277, Cys307, Phe308, Trp345, Lys414, and
      beta-->alpha loop 1 of (beta/alpha)(8) barrel of YicI have been identified as
      elements that might be important for YicI substrate specificity. In attempt to
      convert YicI into an alpha-glucosidase these elements have been targeted by site
      directed mutagenesis. Two mutated YicI, short loop1-enzyme and C307I/F308D,
      showed higher alpha-glucosidase activity than wild-type YicI. C307I/F308D, which
      lost alpha-xylosidase activity, was converted into alpha-glucosidase.

PMID- 16631752
TI  - A kinase independent function for Tec kinase ITK in regulating antigen receptor
      induced serum response factor activation.
AB  - The Tec family kinases are critical downstream regulators of antigen receptor
      signals in lymphocytes. As kinases, they act on critical substrates to regulate
      signals such as calcium increase leading to activation of transcription factors
      such as NFAT, NFkappaB and SRF. We now show here that ITK, a member of the Tec
      family of tyrosine kinases, has a kinase independent function. Mutants of ITK
      that lack kinase activity or a kinase domain can rescue cells lacking Tec family
      kinases for antigen receptor induced SRF activation, but not for NFAT, AP-1 or
      NFkappaB activation. Furthermore, expression of these mutants in WT cells
      enhanced SRF activation. This kinase independent function required the SH2 domain
      since a mutant lacking both the kinase and SH2 domains was much less effective at
      rescuing SRF activation. This kinase-deleted mutant could partially rescue ERK
      activation, and interact with multiple tyrosine phosphorylated proteins during
      antigen receptor signaling, suggesting that ITK uses a scaffolding function that
      regulates signals leading to specific regulation of SRF activation.

PMID- 16631753
TI  - Biology of vascular endothelial growth factors.
AB  - Angiogenesis is the process by which new blood vessels are formed from existing
      vessels. The vascular endothelial growth factors (VEGFs) are considered as key
      molecules in the process of angiogenesis. The VEGF family currently includes VEGF
      A, -B, -C, -D, -E, -F and placenta growth factor (PlGF), that bind in a distinct
      pattern to three structurally related receptor tyrosine kinases, denoted VEGF
      receptor-1, -2, and -3. VEGF-C and VEGF-D also play a crucial role in the process
      of lymphangiogenesis. Here, we review the biology of VEGFs and evaluate their
      role in pathological angiogenesis and lymphangiogenesis.

PMID- 16631754
TI  - Molecular pathology of breast apocrine carcinomas: a protein expression signature
      specific for benign apocrine metaplasia.
AB  - Breast cancer is a heterogeneous disease that encompasses a wide range of
      histopathological types including: invasive ductal carcinoma, lobular carcinoma,
      medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine
      carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all
      invasive breast cancers according to the Danish Breast Cancer Cooperative Group
      Registry, and despite the fact that they are morphologically distinct from other
      breast lesions, there are at present no standard molecular criteria available for
      their diagnosis. In addition, the relationship between benign apocrine changes
      and breast carcinoma is unclear and has been a matter of discussion for many
      years. Recent proteome expression profiling studies of breast apocrine
      macrocysts, normal breast tissue, and breast tumours have identified specific
      apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and
      hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early
      and advanced apocrine lesions. These biomarkers in combination with proteins
      found to be characteristically upregulated in pure apocrine carcinomas
      (psoriasin, S100A9, and p53) provide a protein expression signature distinctive
      for benign apocrine metaplasias and apocrine cystic lesions. These studies have
      also presented compelling evidence for a direct link, through the expression of
      the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and
      pure apocrine carcinomas. Moreover, specific antibodies against the components of
      the expression signature have identified precursor lesions in the linear
      histological progression to apocrine carcinoma. Finally, the identification of
      proteins that characterize the early stages of mammary apocrine differentiation
      such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a
      window of opportunity for pharmacological intervention, not only in a therapeutic
      manner but also in a chemopreventive setting. Here we review published and recent
      results in the context of the current state of research on breast apocrine
      cancer.

PMID- 16631755
TI  - Protein kinase PKC delta and c-Abl are required for mitochondrial apoptosis
      induction by genotoxic stress in the absence of p53, p73 and Fas receptor.
AB  - Doxorubicin, cis-diamminedichloroplatinum (II) and 5-fluorouracil used in
      chemotherapy induce apoptosis in Hep3B cells in the absence of p53, p73, and
      functional Fas. Since mediators remain unknown, the requirement of PKC delta
      (PKCdelta) and c-Abl was investigated. Suppression of c-Abl or PKCdelta
      expression using SiRNAs impaired PARP cleavage, Gleevec and/or rottlerin
      inhibited the induction of the subG1 phase and the increase of reactive oxygen
      species level. Co-precipitations and phosphorylations to mitochondria of c-Abl,
      PKCdelta and Bcl-X(L/s) were induced. A depolarization of the mitochondrial
      membrane and activations of caspase-2 and -9 were observed. We propose that, in
      the absence of p53, p73 and Fas, genotoxic drugs could require both PKCdelta and
      c-Abl to induce apoptosis through the mitochondrial pathway.

PMID- 16631756
TI  - Molecular cloning of a cDNA encoding a crustacean hyperglycemic hormone from
      eyestalk ganglia of the blue crab, Callinectes sapidus.
AB  - Crustacean hyperglycemic hormone (CHH), a polypeptide with multiple physiological
      effects, was first identified in the X-organ/sinus gland neurosecretory system of
      the eyestalks. In studies reported here, we used a PCR-based cloning strategy (RT
      PCR followed by 5'- and 3'-RACE) to clone from blue crab (Callinectes sapidus)
      eyestalk ganglia a cDNA (CsCHH-1) encoding a putative CHH preprohormone. Sequence
      analysis revealed the preprohormone included all structural features previously
      reported for CHH preprohormones: a signal peptide, a CHH precursor-related
      peptide (CPRP), the CHH polypeptide, and a C-terminal basic processing site.
      Further, the deduced amino acid sequence of the mature polypeptide included all
      signature domains previously reported for CHH. The primary structure of blue crab
      CHH is most closely related to CHH from other brachyurans. RT-PCR revealed the
      CsCHH-1 transcript was present in eyestalk ganglia, but was undetectable in other
      tissues tested. A transcript encoding a similar CHH-like preprohormone was
      detected in thoracic ganglion, ventral nerve cord, and brain, but was not
      detected in eyestalk ganglia.

PMID- 16631757
TI  - Salivary testosterone and aggression, delinquency, and social dominance in a
      population-based longitudinal study of adolescent males.
AB  - Testosterone (T) has been found to have a stimulating effect on aggressive
      behavior in a wide range of vertebrate species. There is also some evidence of a
      positive relationship in humans, albeit less consistently. In the present study
      we investigated the relationship between T and aggression, dominance and
      delinquency over time, covering a period from early adolescence to adulthood.
      From a large population-based sample (n = 1.161) a subgroup of 96 boys was
      selected whose behavior had been assessed repeatedly by different informants from
      age 12 to 21 years, and who had provided multiple T samples over these years of
      assessment. On the whole, a decrease in aggressive and delinquent behavior was
      observed in a period in which T rises dramatically. Boys who developed a criminal
      record, had higher T levels at age 16. In addition, positive associations were
      observed between T and proactive and reactive aggression and self-reported
      delinquent behavior. Over the pubertal years different forms of aggressive and
      delinquent behavior were positively related to T, which may indicate that
      specific positive links are dependent on the social setting in which this
      relationship is assessed.

PMID- 16631758
TI  - Conditioning properties of social subordination in rats: behavioral and
      biochemical correlates of anxiety.
AB  - To develop a socially based model of anxiety, the contextual fear conditioning
      properties of social defeat were examined in rats. Social threat consisted of
      exposing intruders to aggressive residents in resident home cage, separated by a
      partition. During 3 daily encounters, intruders were either defeated or
      threatened by residents, providing the defeated-threatened (DT) and threatened
      threatened (TT) groups respectively. On Day 4, both DT and TT animals were
      subjected to a social threat only. Additional animals received a 4-day exposure
      to a novel empty cage (EC group). Further DT, TT, and EC rats were confronted to
      a different context on Day 4. DT rats exhibited a robust and context-specific
      anxiety-like response, characterized by significant behavioral and biochemical
      alterations. DT rats showed increased risk assessment and decreased exploration
      compared to TT and EC rats that in turn were not different towards each other. DT
      and TT rats exhibited increased ACTH levels, while only DT rats showed enhanced
      corticosterone and decreased testosterone levels compared to EC. These
      differences were context-specific since they were absent confronting animals to a
      different context and since they were not long lasting. Overall, these data
      demonstrate the induction of an anxiety-like state in rats through a context
      conditioning process based upon social factors. The social basis of this paradigm
      offers good face validity with anxiety disorders, which in humans are mainly
      related to social factors and associated with HPA axis deregulations. The present
      procedure may provide a useful experimental model to further investigate the
      neurobiological mechanisms underlying anxiety-related disorders.

PMID- 16631759
TI  - Portfolios and the assessment of competence in nursing: a literature review.
AB  - OBJECTIVES: The purpose of this paper is to explore the literature on the
      portfolio as a tool for the assessment of competence in nurse education. DESIGN:
      Literature reviews are a valuable source of information; by locating, appraising
      and synthesising evidence from primary studies they can provide reliable answers
      to focused questions. They can also help to plan new research by identifying both
      what is known and not known in a given area. Literature reviews adhere to a
      scientific methodology which seeks to minimise bias and errors generating
      inferences based on the synthesis of best available evidence. DATA SOURCES: The
      literature review was conducted utilising several databases, selected because of
      their relevance to the subject under review and including CINAHL and MEDLINE as
      well as a hand search of relevant journals and documents. The search terms
      included: nurses in education, portfolios and assessment and competence. Articles
      were included in the review if they focused on portfolios as a method of
      assessment in nurse education and if they were published after 1993 when
      portfolios first appeared in the nursing literature. REVIEW METHODS: The review
      divides the literature into content themes allowing synthesis of the subject
      looking at consistencies and differences, followed by a summary and key arguments
      relating to the next theme. RESULTS: Results highlight the importance of clear
      guidelines for portfolio construction and assessment, the importance of tri
      partite support during portfolio development and guidelines for qualitative
      assessment. Where the portfolio process is well developed there are clear links
      to competence in practice. CONCLUSIONS: The evidence on portfolios as a means of
      assessment continues to expand. If educators take on board the lessons learned
      from previous research and apply it to their assessment process, the difficulties
      found at present, in defining and measuring competence may be reduced.

PMID- 16631760
TI  - Impact of job satisfaction components on intent to leave and turnover for
      hospital-based nurses: a review of the research literature.
AB  - BACKGROUND: The United Kingdom (UK), alongside other industrialised countries, is
      experiencing a shortage of nurses partly due to low retention rates. Job
      satisfaction has been highlighted as a contributing factor to intent to leave and
      turnover, yet this is a complex area with many elements affecting its
      measurement. AIM: The aim of this paper is to explore the impact of job
      satisfaction components on intent to leave and turnover for hospital-based nurses
      in order to identify the most influential factors. METHODS: To achieve this, a
      systematic search of the literature was undertaken to identify relevant
      international research. Three databases (i.e. BNI, CINAHL and PsychInfo) were
      utilised, resulting in nine articles that met the inclusion criteria. Four
      recurrent themes were identified in the literature: leadership, educational
      attainment, pay and stress. FINDINGS: The key findings suggest that stress and
      leadership issues continue to exert influence on dissatisfaction and turnover for
      nurses. Level of education achieved and pay were found to be associated with job
      satisfaction, although the results for these factors were not consistent.
      CONCLUSION: Investigating possible changes over time in sources of
      dissatisfaction revealed that factors related to the work environment rather than
      individual or demographic factors were still of most importance to nurses'
      turnover intentions. The differences found to occur across work settings
      necessitates analysis of job satisfaction at ward level, and the contribution of
      qualitative methods to develop more detailed insight is emphasised. The
      inconsistent findings over time associated with the effects of educational
      attainment and pay on intent to leave suggest that it is imperative that sources
      of job satisfaction are reassessed in the light of ongoing changes.

PMID- 16631761
TI  - A simple fluid-mechanical model for the prediction of the stress-strain relation
      of the male urinary bladder.
AB  - The non-linear, viscoelastic behavior of the male urinary bladder complicates the
      formulation of suitable stress-strain relations for the quasi-static filling
      process and the unsteady voiding process. In particular, the voiding process
      which, in addition, is affected by contraction of muscles leading to generation
      of bladder wall tension-makes it difficult to obtain quantitative results. In the
      present study, a simple model is developed that uses certain urological data from
      cystometry and uroflowmetry to determine the stress-strain relations of the
      bladder wall during both filling and voiding.

PMID- 16631762
TI  - Separation and characterization of silybin, isosilybin, silydianin and
      silychristin in milk thistle extract by liquid chromatography-electrospray tandem
      mass spectrometry.
AB  - A selective and sensitive liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method has been developed for the characterization of silymarin in
      commercially available milk thistle extract. In this study, six main active
      constituents, including silydianin, silychristin, diastereomers of silybin
      (silybin A and B) and diastereomers of isosilybin (isosilybin A and B) in
      silymarin, were completely separated on a YMC ODS-AQ HPLC column using a gradient
      mobile phase system comprised of ammonium acetate and methanol/water/formic acid.
      Identification and characterization of the major constituents were based not only
      on the product ion scan, which provided unique fragmentation information of a
      selected molecular ion, but also on the specific fragmentation of multiple
      reaction monitoring (MRM) data, which confirmed the retention times of LC
      chromatographic peaks. The method was applied in the analysis of human plasma
      samples in the presence of silymarin and appeared to be suitable for the
      pharmacokinetic studies in which the discrimination of silymarin constituents is
      essential.

PMID- 16631763
TI  - Rapid and simplified method for the analysis of polychloronaphthalene congener
      distributions in environmental and human samples by gas chromatography coupled to
      negative ion chemical ionization mass spectrometry.
AB  - A method for the analysis of congener-specific polychloronaphthalene mixtures in
      sediments and human sera based on combined applications of gas chromatography
      coupled to negative ion chemical ionization mass spectrometry (GC-NICI-MS) is
      described. Separation, identification and quantification of the constituent
      congeners is achieved in both types of samples. Besides the octa- and
      heptachloronaphthalenes the method allows the identification of 9
      hexachloronaphthalene congeners, 12 pentachloronaphthalenes and 8
      tetrachloronaphthalenes. Detection and quantification limits were in the order of
      0.4-0.7 ng g-1 dry weight and 0.9-1.3 ng g-1 dry weight in sediments,
      respectively, and 0.06-0.11 ng mL-1 and 0.18-0.21 ng mL-1 in human sera,
      respectively. Application of the method to study the distributions of these
      compounds nearby a chlor-alkali plant located at the shore of the Ebro River has
      shown that whereas the most chlorinated compounds, octachloronaphthalene and the
      two heptachloronaphthalenes were dominant in the sediments, tri-, tetra-, penta-
      and hexachloronaphthalenes were the most abundant congeners found in human sera.

PMID- 16631764
TI  - Determination of chloramphenicol residues in meat, seafood, egg, honey, milk,
      plasma and urine with liquid chromatography-tandem mass spectrometry, and the
      validation of the method based on 2002/657/EC.
AB  - A simple and rapid method for the determination and confirmation of
      chloramphenicol in several food matrices with LC-MS/MS was developed. Following
      addition of d5-chloramphenicol as internal standard, meat, seafood, egg, honey
      and milk samples were extracted with acetonitrile. Chloroform was then added to
      remove water. After evaporation, the residues were reconstituted in
      methanol/water (3+4) before injection. The urine and plasma samples were after
      addition of internal standard applied to a Chem Elut extraction cartridge, eluted
      with ethyl acetate, and hexane washed. Also these samples were reconstituted in
      methanol/water (3+4) after evaporation. By using an MRM acquisition method in
      negative ionization mode, the transitions 321-->152, 321-->194 and 326-->157 were
      used for quantification, confirmation and internal standard, respectively.
      Quantification of chloramphenicol positive samples regardless of matrix could be
      achieved with a common water based calibration curve. The validation of the
      method was based on EU-decision 2002/657 and different ways of calculating
      CCalpha and CCbeta were evaluated. The common CCalpha and CCbeta for all matrices
      were 0.02 and 0.04 microg/kg for the 321-->152 ion transition, and 0.02 and 0.03
      microg/kg for the 321-->194 ion transition. At fortification level 0.1 microg/kg
      the within-laboratory reproducibility is below 25%.

PMID- 16631765
TI  - Preparation of single-enantiomer 2-methyl-4-heptanol, a pheromone of Metamasius
      hemipterus, using (S)-2-methoxy-2-(1-naphthyl)propionic acid.
AB  - To investigate the resolution of secondary alcohols using 2-methoxy-2-(1
      naphthyl)propionic acid (MalphaNP acid), 2-methyl-4-heptanol, one of the
      aggregation pheromones of Metamasius hemipterus, was resolved using (S)-MalphaNP
      acid. As a chiral-resolving agent, MalphaNP acid is superior to 3,3,3-trifluoro-2
      methoxy-2-phenylpropionic acid (MTPA) in terms of HPLC separation and NMR
      shielding. A better separation of diastereomeric MalphaNP esters was observed
      when n-hexane-THF was used as the eluent for silica gel HPLC. The solvolysis of
      the diastereomeric MalphaNP esters gave (R)-2-methyl-4-heptanol and its
      enantiomer; enantiopure (S)-MalphaNP acid was also recovered. In addition, the
      preferred conformation of the MalphaNP ester was confirmed using methyl (R)-3
      hydroxyvalerate as an authentic compound.

PMID- 16631767
TI  - Characterization of concentrated colloidal ceramics suspension: a new approach.
AB  - The dispersion behavior of a concentrated ceramic suspension (Al(2)O(3)) has been
      investigated in terms of capillary suction time (CST) with varying solids
      concentration both in the absence as well as in the presence of dispersant (APC).
      The CST value is found to be the lowest at the pH(iep) whereas it increases as
      the pH is changed either to the acid side or alkaline side due to the repulsive
      forces acting among the neighboring particles keeping them in more dispersed
      state. It has been further observed that the CST value increases with increasing
      concentration of solids in the suspension. The dispersability of the suspension
      has been quantified in terms of dispersion ratio (DR). The higher the dispersion
      ratio of a particular system above unity, the better is the dispersability and
      vice versa. Further, quantification of dispersion stability by the CST technique
      is found to be useful and practical for optimization of different parameters
      concerning suspension stability. A correlation is found among the CST, zeta
      potential, colloidal stability, and maximum solids loading. It has been finally
      concluded that the CST method could be potentially employed as a quantitative and
      diagnostic technique for characterizing concentrated ceramic suspension.

PMID- 16631768
TI  - Formation and electrochemical characterization of 6-thioguanosine monolayers on
      the mercury surface.
AB  - The interfacial and electrochemical behavior of 6-thioguanosine-6-thioguanine
      riboside (6TGR)-on a hanging mercury drop electrode was studied with ac and
      cyclic voltammetry in a solution of 0.1 M Na(2)SO(4) and 0.01 M sodium acetate
      buffer at pH 4.3. A self-assembled monolayer (SAM) of chemisorbed 6TGR molecules
      formed under determined adsorption conditions was characterized. A low-density
      monolayer of chemisorbed 6TGR molecules and a condensed monolayer of physisorbed
      ones, which are successively formed by reduction of the SAM, were also studied.

PMID- 16631769
TI  - Temperature effect on water intrusion/expulsion in grafted silica gels.
AB  - Water intrusion-expulsion cycles within a hydrophobic silica gel system were
      observed at various temperatures. The hysteresis phenomenon revealed an
      attenuation effect growing with temperature. A simple model derived from the
      Laplace-Washburn equation made it possible to characterize the observed phenomena
      both qualitatively and quantitatively. The model involves advancing and receding
      contact angles increasing with temperature, which influence the hysteresis
      phenomenon very differently, depending on their value.

PMID- 16631770
TI  - Measurement and modeling of the surface potential evolution of hydrated cement
      pastes as a function of degradation.
AB  - Hydrated cement pastes (HCP) have a high affinity with a lot of (radio)toxic
      products and can be used as waste confining materials. In cementitious media,
      elements are removed from solution via (co)precipitation reactions or via
      sorption/diffusion mechanisms as surface complexation equilibria. In this study,
      to improve the knowledge of the surface charge evolution vs the degradation of
      the HCP particles, two cements have been studied: CEM-I (ordinary Portland
      cement, OPC) and CEM-V (blast furnace slag and fly ash added to OPC). Zeta
      potential measurements showed that two isoelectric points exist vs HCP leaching,
      i.e., pH. Zeta potential increases from -17 to +20 mV for pH 13.3 to pH 12.65
      (fresh HCP states) and decreases from 20 to -8 mV for pH 12.65 to 11 (degraded
      HCP states). The use of a simple surface complexation model of C-S-H, limited in
      comparison with the structural modeling of C-S-H in literature, allows a good
      prediction of the surface potential evolution of both HCP. Using this operational
      modeling, the surface charge is controlled by the deprotonation of surface sites
      (>SO(-)) and by the sorption of calcium (>SOCa(+)), which brings in addition a
      positive charge. The calcium concentration is controlled by portlandite or
      calcium silicate hydrate (C-S-H) solubilities.

PMID- 16631771
TI  - Preparation and characterization of long-lived anode catalyst for direct methanol
      fuel cells.
AB  - Entry of direct methanol fuel cells into the market requires anode catalyst with
      stable activity. This paper presents a novel method for stabilizing the activity
      by immobilizing silica on the catalytic PtRu nanoparticles. Characterization was
      performed by STEM-EDX, XRD, and ICP. The silica-immobilized PtRu nanoparticles
      showed high and stable activity toward methanol oxidation. The activity was
      maintained for 1000 h in sulfuric acidic solution, while the activity of the
      catalyst with "bare" PtRu nanoparticles decayed after 100 h, showing high
      durability of the silica-immobilized PtRu nanoparticles catalyst in quasi-anodic
      acidic environment.

PMID- 16631772
TI  - Strontium binding by calcium silicate hydrates.
AB  - In the present study the binding of strontium with pure calcium silicate hydrates
      (C-S-H) has been investigated using batch-type experiments. Synthetic C-S-H
      phases with varying CaO:SiO(2) (C:S) mol ratios, relevant to non-degraded and
      degraded hardened cement paste, were prepared in the absence of alkalis (Na(I),
      K(I)) and in an alkali-rich artificial cement pore water (ACW). Two types of
      experimental approaches have been employed, investigating sorption and co
      precipitation processes, respectively. The Sr(II) sorption kinetics were
      determined as well as sorption isotherms, the effect of the solid to liquid ratio
      and the composition (C:S ratio) of the C-S-H phases. In addition, the
      reversibility of the Sr(II) sorption was tested. It was shown that both the
      sorption and co-precipitation tests resulted in Sr(II) distribution ratios which
      were similar in value, indicating that the same sites are involved in Sr(II)
      binding. In alkali-free solutions, the Sr(II) uptake by C-S-H phases was
      described in terms of a Sr(2+)-Ca(2+) ion exchange model. The selectivity
      coefficient for the Sr(2+)-Ca(2+) exchange was determined to be 1.2+/-0.3.

PMID- 16631773
TI  - Effect of temperature on dynamic rheological behavior of discontinuous cubic
      liquid crystal.
AB  - The dynamic rheological properties of discontinuous cubic liquid crystal, formed
      by nonionic surfactant C(12-14)E(12), were investigated in the discrete and
      continuous patterns of raising temperature. In the discrete pattern, the
      discontinuous cubic phase appears in two types of viscoelastic behaviors under
      the melting points of cubic phase: elastic gel and viscoelastic liquid. When the
      discontinuous cubic phase begins to melt, it has the weak polymer-like
      viscoelasticity. Temperature and shear frequency have completely different
      effects on the ratio of viscous and elastic components of samples in these three
      states. At low temperature, the samples dominate in elasticity and temperature
      and shear frequency has hardly any effect on viscoelasticity. At moderate
      temperature, its ratio of viscous and elastic components increases with
      increasing temperature and decreasing shear frequency. At the vicinity of the
      melting point of cubic liquid crystal, the cubic liquid crystal appears to have
      almost equaled viscous and elastic component; shear has obvious effect on the
      ratio of viscoelasticity at low frequency. The results from the continuous
      pattern of raising temperature are consistent with those from the discrete
      pattern.

PMID- 16631774
TI  - A modeling approach to describe the adhesion of rough, asymmetric particles to
      surfaces.
AB  - A combined theoretical and experimental study of the adhesion of alumina
      particles and polystyrene latex spheres to silicon dioxide surfaces was
      performed. A boundary element technique was used to model electrostatic
      interactions between micron-scale particles and planar surfaces when the
      particles and surfaces were in contact. This method allows quantitative
      evaluation of the effects of particle geometry and surface roughness on the
      electrostatic interaction. The electrostatic interactions are combined with a
      previously developed model for van der Waals forces in particle adhesion. The
      combined model accounts for the effects of particle and substrate geometry,
      surface roughness and asperity deformation on the adhesion force. Predictions
      from the combined model are compared with experimental measurements made with an
      atomic force microscope. Measurements are made in aqueous solutions of varying
      ionic strength and solution pH. While van der Waals forces are generally dominant
      when particles are in contact with surfaces, results obtained here indicate that
      electrostatic interactions contribute to the overall adhesion force in certain
      cases. Specifically, alumina particles with complex geometries were found to
      adhere to surfaces due to both electrostatic and van der Waals interactions,
      while polystyrene latex spheres were not affected by electrostatic forces when in
      contact with various surfaces.

PMID- 16631775
TI  - Two-dimensional "nano-ring and nano-crystal" morphologies in Langmuir monolayer
      of phthalocyaninato nickel complexes.
AB  - Three 1,8,15,22-tetrasubstituted phthalocyaninato nickel complexes Ni[Pc(alpha
      OR)(4)] [H(2)Pc(alpha-OC(5)H(11))(4) = 1,8,15,22-tetrakis(3
      pentyloxy)phthalocyanine; H(2)Pc(alpha-OC(7)H(15))(4) = 1,8,15,22-tetrakis(2,4
      dimethyl-3-pentyloxy)phthalocyanine; H(2)Pc(alpha-OC(10)H(7))(4) = 1,8,15,22
      tetrakis(2-naphthyloxy)phthalocyanine] (1-3) have been prepared by treating the
      corresponding metal-free phthalocyanines H(2)Pc(alpha-OR)(4) with
      Ni(acac)(2)2H(2)O in refluxing n-pentanol. Structures of the Langmuir monolayers
      of these compounds at different temperature have been investigated. Compound 1
      formed nano-ring structures with the outer diameter of 70-150 nm and inner
      diameter of 50 nm at 25.0 degrees C while 2 and 3 formed round particles. This
      difference can be ascribed to the different substituents at alpha position. The
      morphologies of the aggregates of 1 in monolayers have been found to change with
      temperature. Decreasing in temperature induced the formation of regular quadrate
      crystals. UV-vis absorption spectra revealed strong intermolecular interactions
      in the nano-ring aggregates. Polarized UV-vis absorption spectra suggest a titled
      orientation with respect to the surface of substrate for phthalocyanine
      macrocycles in the nano-ring aggregates.

PMID- 16631776
TI  - Au-Pt bimetallic nanoparticles formation via viologen-mediated reduction on
      polymeric nanospheres.
AB  - Poly(vinylbenzyl chloride) nanospheres prepared via emulsion polymerization were
      surface functionalized with viologen moieties. Several methods were investigated
      to achieve the desired high surface concentration of viologen moieties with
      minimal aggregation of the nanospheres. The viologen-functionalized nanospheres
      were used for photoinduced reduction of gold ions and platinum ions, either
      individually, simultaneously or sequentially, to result in the formation of well
      distributed Au-Pt nanoparticles of a few nanometers on the surface of the
      nanospheres. UV-visible absorption spectroscopy and XPS analyses of these
      bimetallic nanoparticles were carried out. The reaction time and the sequence of
      the reduction process play an important role in determining the composition of
      the bimetallic nanoparticles. High-resolution transmission electron microscopy
      analysis reveals the highly crystalline nature of the bimetallic nanoparticles.

PMID- 16631777
TI  - Aggregation of quaternary ammonium gemini surfactants C12-s-C12.2Br in n
      heptane/n-hexanol solution: effect of the spacer chains on the critical reverse
      micelle concentrations.
AB  - The critical reverse micelle concentrations of C(12)-s-C(12).2Br
      (s=2,3,4,5,6,8,12) in n-heptane/n-hexanol solutions, cmc(I)s, have been
      determined by absorption spectrum method using iodine as probe. The values of
      cmc(I)s are smaller than those of the critical micelle concentrations (cmc(aq)s)
      in aqueous solution and reach a maximum at s=4, which is similar to the variation
      of cmc(aq) with s. The variation of cmc(I) with s is attributed to the alteration
      in the spacer chain conformation, i.e. when the spacer is short enough, it may
      adopt stretch configuration and when the spacer is long, it tends to bend towards
      the continuous oil phase to achieve a more densely packing of the quaternary
      ammonium heads on the surface of the core.

PMID- 16631778
TI  - The similarity of electric double-layer interaction from the general Poisson
      Boltzmann theory.
AB  - We studied electric double-layer (EDL) interactions in electrolytes with
      different valence combinations. Our results show that the interactions are
      similar for electrolytes with the same co-ion valences and concentrations and
      such similarity increases with the co-ion valence and surface potential. A scaled
      surface potential was defined and found to be useful in characterizing the
      difference in EDL interaction. These results show that co-ions play a more
      important role than counterions in determining EDL potential and interaction in
      an electrolyte solution, especially for systems with high co-ion valence and/or
      high surface potentials.

PMID- 16631779
TI  - Gelation and internal dynamics of colloidal rod aggregates.
AB  - The internal dynamics of fractal cluster gels of colloidal boehmite rods with
      aspect ratios r = 3.9, 8.6, and 30.1, and colloidal polystyrene spheres (r = 1)
      are reported. Increasing r decreases the minimum colloid volume fraction for
      gelation. The behavior of the dynamic structure factor of rod gels is consistent
      with the internal dynamics of a constrained Brownian fractal object. Colloidal
      boehmite gels display an abrupt transition from floppy to brittle dynamics at phi
      approximately 10(-4). Moreover, the fractal cluster size of rod gels is not the
      determinant of the relaxation time of density fluctuations as it is in spherical
      particle gels. Instead, the relative behavior of the magnitude and time scale of
      the constrained fluctuations suggests that the fractal rod network is viscously
      coupled only on local, rather than cluster, scales. We hypothesize that
      noncentral forces between the anisometric particles are responsible for this
      anomalous behavior.

PMID- 16631780
TI  - Preparation of highly monodisperse W/O emulsions with hydrophobically modified
      SPG membranes.
AB  - Experimental investigations on the hydrophobic modification of SPG membranes and
      the preparation of monodisperse W/O (water-in-oil) emulsions using the modified
      membranes were carried out. Effects of the osmotic pressure of disperse phase,
      the average pore size of membranes, emulsifier concentrations in continuous phase
      and the transmembrane pressure on the average size, size distribution and size
      dispersion coefficient of emulsions were systematically studied. The stability of
      W/O emulsions was also investigated. The results showed that SPG membranes took
      on excellent hydrophobicity through the modification by silane coupler reagent
      (octyltriethoxysilane) or by silicone resin (polymethylsilsesquioxane).
      Monodisperse W/O emulsions with size dispersion coefficient of about 0.25, which
      meant high monodispersity, were successfully prepared by using the
      hydrophobically modified SPG membranes with average pore sizes of 1.8, 2.0, 2.5,
      4.8 and 11.1 microm. When the osmotic pressure was lower than 0.855 MPa, the
      average size of emulsions was gradually increased while the size dispersion
      coefficient delta gradually decreased with the osmotic pressure; when the osmotic
      pressure was higher than 0.855 MPa, both the coefficients kept unvarying. When
      kerosene was saturated with disperse phase in advance, the average size of
      emulsions became larger and the monodispersity of emulsions was slightly better
      than that prepared using unsaturated kerosene. The smaller the pore size of SPG
      membranes was, the better the monodispersity of the W/O emulsions. The average
      size and size dispersion coefficient delta were nearly independent on the
      emulsifier concentrations when the PGPR concentration was in the range from 0.5
      to 5.0 wt%, whereas both of them slightly increased as the PGPR concentration was
      below 0.5 wt%. The effect of the transmembrane pressure on size distributions was
      slight. Both the average size and size dispersion coefficient delta slightly
      increased to some extent with the increase of the transmembrane pressure in the
      experimental range. The stability of the W/O emulsions was dependent on the
      storage time. The mean size of W/O emulsions decreased gradually with the
      increase of storage time at the first 35 days, and then kept constant; while the
      size dispersion coefficient of W/O emulsions was nearly not changed.

PMID- 16631781
TI  - The physics of moving wetting lines.
AB  - Scientists tend to think in terms of their most familiar models. It is not
      accidental that the earliest descriptions of the moving wetting line and its
      associated dynamic contact angle were in terms of displaced equilibria
      (chemists), friction (physicists) and viscous bending of the liquid-vapour
      interface (engineers and mathematicians). Each of these approaches has progressed
      since its inception, but, while each reflects a different facet of the underlying
      physical mechanism, and each offers at least a semi-empirical route to its
      description, none is complete. There is, as yet, no fully agreed treatment that
      is consistent with all three viewpoints and provides an effective basis for
      prediction -- though at least one new hydrodynamic approach has emerged that goes
      some way in this direction. This paper seeks to offer a status report: to briefly
      review each of the current approaches, to illustrate their successes and
      limitations as revealed by experiment and simulation, and to suggest ways in
      which the different aspects of wetting dynamics might be investigated in the
      future.

PMID- 16631782
TI  - An ionic polymer bead-supported lipid system.
AB  - In this paper, we report on the preparation of an ionic polymer bead-supported
      lipid system several hundred micrometers in diameter. The electrostatic
      attractive interactions between anionic lipids and cationic polymer beads served
      as a "molecular glue" to immobilize the lipids on the beads, and then the
      immobilized lipids prompted the spontaneous formation of lipid bilayer membranes.
      Confocal fluorescence microscopic techniques revealed that the lipid bilayer
      membranes were located along the outline of the beads. In addition, the integrity
      of the lipid bilayer membranes was microscopically confirmed by a low-molecular
      weight dye (trypan blue) exclusion test.

PMID- 16631783
TI  - Generalization of Kelvin's equation for compressible liquids in nanoconfinement.
AB  - The Kelvin equation for a compressible liquid in nanoconfinement is written in a
      form that takes into account not only Laplace's pressure, but also the
      oscillatory compression pressure. This leads to a simple analytical equation for
      pressure in nanocapillaries. The corrected equation is used to analyze properties
      of aqueous systems, including the oscillatory structural forces between
      attractive surfaces and inert surfaces, repulsive "hydration" forces between
      hydrophilic surfaces, and attractive "hydrophobic" forces between hydrophobic
      surfaces. Relative vapor pressure in a nanocapillary also is discussed.

PMID- 16631784
TI  - Surface characterizations of mono-, di-, and tri-aminosilane treated glass
      substrates.
AB  - The surface properties and structure of mono-, di-, and tri-aminosilane treated
      glass surfaces were investigated using surface analytical techniques including X
      ray photoelectron spectroscopy (XPS), Raman spectroscopy, atomic force microscopy
      (AFM), and streaming potential. An optimized dip-coating process was demonstrated
      to produce roughly silane monolayer coverage on the glass surface. The surface
      charge measurements indicated that aminosilanization converts the glass surface
      from negative to positive potentials at neutral pH values. Higher positive
      streaming potential was observed for tri-compared with mono- and di-aminosilane
      treated glass surfaces. For all aminosilane treated glass samples, the high
      resolution N 1s XPS spectra indicated a preferential orientation of the
      protonated amino-groups towards the glass surface whereas the free amino groups
      were protruding outward. This study aimed to obtain uniform, reproducibly thin,
      strongly adhering, internally cross-linked, and high positively charged
      aminosilane-coated glass surfaces for the attachment of DNA fragments used in
      microarraying experiments.

PMID- 16631785
TI  - The first holocomplex structure of ribonucleotide reductase gives new insight
      into its mechanism of action.
AB  - Ribonucleotide reductase is an indispensable enzyme for all cells, since it
      catalyses the biosynthesis of the precursors necessary for both building and
      repairing DNA. The ribonucleotide reductase class I enzymes, present in all
      mammals as well as in many prokaryotes and DNA viruses, are composed mostly of
      two homodimeric proteins, R1 and R2. The reaction involves long-range radical
      transfer between the two proteins. Here, we present the first crystal structure
      of a ribonucleotide reductase R1/R2 holocomplex. The biological relevance of this
      complex is based on the binding of the R2 C terminus in the hydrophobic cleft of
      R1, an interaction proven to be crucial for enzyme activity, and by the fact that
      all conserved amino acid residues in R2 are facing the R1 active sites. We
      suggest that the asymmetric R1/R2 complex observed in the 4A crystal structure of
      Salmonella typhimurium ribonucleotide reductase represents an intermediate stage
      in the reaction cycle, and at the moment of reaction the homodimers transiently
      form a tight symmetric complex.

PMID- 16631786
TI  - Clustering of RNA secondary structures with application to messenger RNAs.
AB  - There is growing evidence of translational gene regulation at the mRNA level, and
      of the important roles of RNA secondary structure in these regulatory processes.
      Because mRNAs likely exist in a population of structures, the popular free energy
      minimization approach may not be well suited to prediction of mRNA structures in
      studies of post-transcriptional regulation. Here, we describe an alternative
      procedure for the characterization of mRNA structures, in which structures
      sampled from the Boltzmann-weighted ensemble of RNA secondary structures are
      clustered. Based on a random sample of full-length human mRNAs, we find that the
      minimum free energy (MFE) structure often poorly represents the Boltzmann
      ensemble, that the ensemble often contains multiple structural clusters, and that
      the centroids of a small number of structural clusters more effectively
      characterize the ensemble. We show that cluster-level characteristics and
      statistics are statistically reproducible. In a comparison between mRNAs and
      structural RNAs, similarity is observed for the number of clusters and the energy
      gap between the MFE structure and the sampled ensemble. However, for structural
      RNAs, there are more high-frequency base-pairs in both the Boltzmann ensemble and
      the clusters, and the clusters are more compact. The clustering features have
      been incorporated into the Sfold software package for nucleic acid folding and
      design.

PMID- 16631787
TI  - Structural insights into enzyme-substrate interaction and characterization of
      enzymatic intermediates of organic hydroperoxide resistance protein from Xylella
      fastidiosa.
AB  - Organic hydroperoxide resistance proteins (Ohr) belong to a family of proteins
      that possess thiol-dependent peroxidase activity endowed by reactive cysteine
      residues able to reduce peroxides. The crystal structure of Ohr from Xylella
      fastidiosa in complex with polyethylene glycol, providing insights into enzyme
      substrate interactions is described herein. In addition, crystallographic
      studies, molecular modeling and biochemical assays also indicated that peroxides
      derived from long chain fatty acids could be the biological substrates of Ohr.
      Because different oxidation states of the reactive cysteine were present in the
      Ohr structures from X. fastidiosa, Pseudomonas aeruginosa and Deinococcus
      radiodurans it was possible to envisage a set of snapshots along the coordinate
      of the enzyme-catalyzed reaction. The redox intermediates of X. fastidiosa Ohr
      observed in the crystals were further characterized in solution by electrospray
      ionization mass spectrometry and by biochemical approaches. In this study, the
      formation of an intramolecular disulfide bond and oxidative inactivation through
      the formation of a sulfonic acid derivative was unequivocally demonstrated for
      the first time. Because Ohr proteins are exclusively present in bacteria, they
      may represent promising targets for therapeutical drugs. In this regard, the
      structural and functional analyses of Ohr presented here might be very useful.

PMID- 16631788
TI  - Ig-like domains on bacteriophages: a tale of promiscuity and deceit.
AB  - The immunoglobulin (Ig) fold is one of the most important structures in biology,
      playing essential roles in the vertebrate immune response, cell adhesion, and
      many other processes. Through bioinformatic analysis, we have discovered that Ig
      like domains are often found in the constituent proteins of tailed double
      stranded (ds) DNA bacteriophage particles, and are likely displayed on the
      surface of these viruses. These phage Ig-like domains fall into three distinct
      sequence families, which are similar to the classic immunoglobulin domain (I
      Set), the fibronectin type 3 repeat (FN3), and the bacterial Ig-like domain
      (Big2). The phage Ig-like domains are very promiscuous. They are attached to more
      than ten different functional classes of proteins, and found in all three
      morphogenetic classes of tailed dsDNA phages. In addition, they reside in phages
      that infect a diverse set of gram negative and gram positive bacteria. These
      domains are deceptive because many are added to larger proteins through
      programmed ribosomal frameshifting, so that they are not always detected by
      standard protein sequence searching procedures. In addition, the presence of
      unrecognized Ig-like domains in a variety of phage proteins with different
      functions has led to gene misannotation. Our results demonstrate that horizontal
      gene transfer involving Ig-like domain encoding DNA has occurred commonly between
      diverse classes of both lytic and temperate phages, which otherwise display very
      limited sequence similarities to one another. We suggest that phage may have been
      an important vector in the spread of Ig-like domains through diverse species of
      bacteria. While the function of the phage Ig-like domains is unknown, several
      lines of evidence suggest that they may play an accessory role in phage infection
      by weakly interacting with carbohydrates on the bacterial cell surface.

PMID- 16631789
TI  - Kinetics of insulin-like growth factor II (IGF-II) interaction with domain 11 of
      the human IGF-II/mannose 6-phosphate receptor: function of CD and AB loop solvent
      exposed residues.
AB  - Ligands of the IGF-II/mannose 6-phosphate receptor (IGF2R) include IGF-II and
      mannose 6-phosphate modified proteins. Disruption of the negative regulatory
      effects of IGF2R on IGF-II-induced growth can lead to embryonic lethality and
      cancer promotion. Of the 15 IGF2R extracellular domains, domains 1-3 and 11 are
      known to have a conserved beta-barrel structure similar to that of avidin and the
      cation-dependent mannose 6-phosphate receptor, yet only domain 11 binds IGF-II
      with high specificity and affinity. In order to define the functional basis of
      this critical biological interaction, we performed alanine mutagenesis of
      structurally determined solvent-exposed loop residues of the IGF-II-binding site
      of human domain 11, expressed these mutant forms in Pichia pastoris, and
      determined binding kinetics with human IGF-II using isothermal calorimetry and
      surface plasmon resonance with transition state thermodynamics. Two hydrophobic
      residues in the CD loop (F1567 and I1572) were essential for binding, with a
      further non-hydrophobic residue (T1570) that slows the dissociation rate. Aside
      from alanine mutations of AB loop residues that decrease affinity by modifying
      dissociation rates (e.g. Y1542), a novel mutation (E1544A) of the AB loop
      enhanced affinity by threefold compared to wild-type. Conversion from an acidic
      to a basic residue at this site (E1544K) results in a sixfold enhancement of
      affinity via modification principally of the association rate, with enhanced salt
      dependence, decreased entropic barrier and retained specificity. These data
      suggest that a functional hydrophobic binding site core is formed by I1572 and
      F1567 located in the CD loop, which initially anchors IGF-II. Within the AB loop,
      residues normally act to either stabilise or function as negative regulators of
      the interaction. These findings have implications for the molecular architecture
      and evolution of the domain 11 IGF-II-binding site, and the potential
      interactions with other domains of IGF2R.

PMID- 16631790
TI  - Solution structure of monomeric BsaL, the type III secretion needle protein of
      Burkholderia pseudomallei.
AB  - Many gram-negative bacteria that are important human pathogens possess type III
      secretion systems as part of their required virulence factor repertoire. During
      the establishment of infection, these pathogens coordinately assemble greater
      than 20 different proteins into a macromolecular structure that spans the
      bacterial inner and outer membranes and, in many respects, resembles and
      functions like a syringe. This type III secretion apparatus (TTSA) is used to
      inject proteins into a host cell's membrane and cytoplasm to subvert normal
      cellular processes. The external portion of the TTSA is a needle that is composed
      of a single type of protein that is polymerized in a helical fashion to form an
      elongated tube with a central channel of 2-3 nm in diameter. TTSA needle proteins
      from a variety of bacterial pathogens share sequence conservation; however, no
      atomic structure for any TTSA needle protein is yet available. Here, we report
      the structure of a TTSA needle protein called BsaL from Burkholderia pseudomallei
      determined by nuclear magnetic resonance (NMR) spectroscopy. The central part of
      the protein assumes a helix-turn-helix core domain with two well-defined alpha
      helices that are joined by an ordered, four-residue linker. This forms a two
      helix bundle that is stabilized by interhelix hydrophobic contacts. Residues that
      flank this presumably exposed core region are not completely disordered, but
      adopt a partial helical conformation. The atomic structure of BsaL and its
      sequence homology with other TTSA needle proteins suggest potentially unique
      structural dynamics that could be linked with a universal mechanism for control
      of type III secretion in diverse gram-negative bacterial pathogens.

PMID- 16631791
TI  - Structural and functional studies of the response regulator HupR.
AB  - HupR is a response regulator that controls the synthesis of the membrane-bound
      [NiFe]hydrogenase of the photosynthetic bacterium Rhodobacter capsulatus. The
      protein belongs to the NtrC subfamily of response regulators and is the second
      protein of a two-component system. We have crystallized the full-length protein
      HupR in the unphosphorylated state in two dimensions using the lipid monolayer
      technique. The 3D structure of negatively stained HupR was calculated to a
      resolution of approximately 23 A from tilted electron microscope images. HupR
      crystallizes as a dimer, and forms an elongated V-shaped structure with extended
      arms. The dimensions of the dimer are about 80 A length, 40 A width and 85 A
      thick. The HupR monomer consists of three domains, N-terminal receiver domain,
      central domain and C-terminal DNA-binding domain. We have fitted the known 3D
      structure of the central domain from NtrC1 Aquifex aeolicus protein into our 3D
      model; we propose that contact between the dimers is through the central domain.
      The N-terminal domain is in contact with the lipid monolayer and is situated on
      the top of the V-shaped structure. The central domain alone has been expressed
      and purified; it forms a pentamer in solution and lacks ATPase activity.

PMID- 16631792
TI  - The importance of RNA structure in RNA editing and a potential proofreading
      mechanism for correct guide RNA:pre-mRNA binary complex formation.
AB  - RNA editing in trypanosomes is a post-transcriptional process responsible for
      correcting the coding sequences of many mitochondrial mRNAs. Uridine bases are
      specifically added or deleted from mRNA by an enzymatic cascade in which a pre
      edited mRNA is cleaved specifically, uridine bases are added or removed, and the
      corrected mRNA is ligated. The process is directed by RNA molecules, termed guide
      RNAs (gRNA). The ability of this class of small, non-coding RNA to function in
      RNA editing is essential for these organisms. Typically, gRNAs are transcribed
      independent of their cognate mRNA and anneal to form a binary RNA complex. An
      exception from this process is the cytochrome oxidase subunit II (COII) mRNA,
      which encodes its gRNA within its 3' untranslated region. This gRNA lacks the
      ability to function in trans. Using an in vitro editing assay, we find that
      improving thermodynamic stability to the anchor region through increased Watson
      Crick base-pairing is sufficient to impart trans editing activity. We further
      show that a point mutation outside the known functional regions of a gRNA induces
      both a conformational rearrangement of the gRNA and causes a decrease in the rate
      of editing. Taken together, these results lead us to propose a model for a
      potential proofreading step in the formation of a gRNA:pre-edited mRNA binary
      complex. The mechanism relies on the thermodynamic stability supplied to the RNA
      complex through Watson-Crick base-pairing. Through mutations in the gRNA, we
      demonstrate the importance of gRNA structure to the RNA editing reaction.

PMID- 16631793
TI  - Co-expressed yeast genes cluster over a long range but are not regularly spaced.
AB  - Analysis in yeast of the relationship between a gene's genomic position and its
      expression profile, derived from chip array data, suggests that both closely
      linked genes and genes spaced at regular intervals show correlated expression
      profiles. Unfortunately, yeast arrays are often printed in genomic order. The
      above results may hence reflect little more than known spatial biases within
      arrays. To circumvent this problem, we analyse spatially unbiased expression data
      derived from a large Northern blot study. We find that local domains of co
      expressed genes range up to 30 genes (100 kb), and are thus much larger than
      previously considered. There is, by contrast, no evidence for periodicity of co
      expression in yeast. We likewise find no convincing evidence for periodicity in
      the human or mouse genome. Further, analysis of yeast transcription factor
      binding data sets suggests that there is currently no statistical evidence for
      chromosomal periodicity of co-regulation.

PMID- 16631794
TI  - Neocortical volume decrease in relapsing-remitting multiple sclerosis with mild
      cognitive impairment.
AB  - The aim of the study was to assess neocortical changes and their relevance to
      cognitive impairment in early relapsing-remitting multiple sclerosis (RRMS).
      Conventional magnetic resonance was acquired in 41 RRMS patients and 16
      demographically matched normal controls (NC). An automated analysis tool was used
      to obtain measures of cortical brain volumes normalized for head size.
      Neuropsychological performance of MS patients was assessed through the Rao's
      Brief Repeatable Battery. We identified 18 cognitively preserved (MS-cp) and 23
      cognitively impaired (MS-ci) MS patients. Values of normalized cortical volumes
      (NCV) in the whole MS sample were lower than those in the NC group (p=0.01). MS
      ci patients showed NCV values lower (p=0.02) than did both MS-cp patients and NC.
      Moreover, we found a positive correlation between NCV values and measures of
      verbal memory (r=0.51, p=0.02), verbal fluency (r=0.51, p=0.01) and
      attention/concentration (r=0.65, p<0.001) in MS-ci patients. Furthermore, NCV
      values were significantly decreased in patients who scored lower on a greater
      number of tests (r=-0.58, p<0.01) in the MS-ci group. Only MS-ci patients had
      cortical atrophy significantly correlated with a poorer neuropsychological
      performance. Grey matter pathology may contribute to the development of cognitive
      impairment in MS from the earliest stages of the disease.

PMID- 16631795
TI  - Reversible restricted diffusion of entire corpus callosum.
AB  - MR imaging of a 31-year-old man with bacterial meningo-encephalitis associated
      with infectious endocarditis demonstrated T2 prolongation and restricted
      diffusion involving the entire corpus callosum and symmetrically involving the
      cerebral hemispheric white matter. His neurological signs and symptoms were mild,
      and recovery was complete within a week. Follow-up MR imaging with a 9-day
      interval revealed complete resolution of these lesions. The clinical and
      radiological courses were identical to those previously reported with a
      reversible lesion isolated to the splenium, or to the splenium and peripheral
      fronto-parietal white matter. This suggests that such reversible lesions are not
      necessarily restricted to the splenium, but may involve the entire corpus
      callosum.

PMID- 16631796
TI  - The impact of our genes: consequences of the apolipoprotein E polymorphism in
      Alzheimer disease and multiple sclerosis.
AB  - Epidemiological studies provide strong evidence that susceptibility to multiple
      sclerosis (MS) is in part genetically determined. Likewise the heterogeneity in
      clinical manifestations, temporal course, severity, and in the pathological
      processes of MS are probably also influenced by our genes. Apolipoprotein E
      (apoE) polymorphism has been considered a candidate for impacting on MS because
      of its numerous functions related to brain tissue and evidence for an association
      with a variety of cerebral disorders, specifically Alzheimer's disease (AD). The
      apoE alleles epsilon2, epsilon3, and epsilon4 are known to impact differently on
      aspects such as neuronal growth and repair, neuroprotection and inflammation.
      After a review of the strong association of the apoE polymorphism with AD, we
      review the results on MS. These are far less homogenous but have gained support
      from morphologic and metabolic measures obtained with magnetic resonance imaging
      indicating a greater extent of brain destruction with the apoE epsilon4 allele.
      Evidence for a protective role of the epsilon2 allele in MS is weak. In view of
      the association with AD it is tempting to speculate that neuropsychologic
      functioning in MS might be even more strongly related to the apoE polymorphism
      and especially to the epsilon4 allele than other deficits, but few data on this
      issue are yet available. While part of the association of the apoE polymorphism
      with AD is supposed to be caused by apoE-isoform dependent effects on amyloid
      beta deposition, no single pathogenetically relevant mechanism has yet been
      confirmed for MS. In summary we presently may assume only subtle effects of the
      apoE polymorphism on the course of MS. These effects are probably further
      modulated by other genes and need further investigation.

PMID- 16631797
TI  - Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for
      myasthenia gravis.
AB  - OBJECTIVE: To elucidate the long-term therapeutic efficacy and safety of low-dose
      FK506 (tacrolimus) in patients with myasthenia gravis (MG). PATIENTS AND METHODS:
      We treated nine patients with MG (all women: age range: 35-83 years (mean: 51.1
      years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients)
      with FK506 for more than 24 months (observation period: 24-46 months). All the
      patients had undergone extended thymectomy before FK506 treatment; two patients
      (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We
      evaluated total Quantitative MG (Q-MG) score, anti-acetylcholine receptor (AChR)
      antibody titer in the blood, interleukin 2 (IL-2) production in peripheral blood
      mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and
      adverse effects of FK506. RESULTS: A reduction in steroid dosage of 50% without
      worsening of the symptoms was observed 1 year after FK506 administration in three
      out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0
      39 points) at 6 months and 1 year after FK506 administration improved by 3 points
      or more in six (66.7%) and seven (77.8%) out of nine patients, respectively. The
      efficacy of FK506 was maintained for more than 2 years. Although adverse effects
      were observed in three patients (33.3%), these were not serious. CONCLUSIONS: Our
      study indicates that low-dose FK506 treatment may be efficacious not only in
      controlling intractable myasthenic symptoms, but also in reducing steroid dosage,
      and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a
      maximum of 3 years.

PMID- 16631798
TI  - Psychiatric onset of multiple sclerosis.
AB  - We present a patient with psychotic disorder as onset of relapsing-remitting
      multiple sclerosis (MS). In this patient, a 26-year-old female, neurological
      examination revealed only minor abnormalities. As cranial CT scan was normal, her
      psychosis was diagnosed as psychogenic. Literature on psychiatric onset of MS is
      reviewed paying special attention to clinical and MRI aspects. It is concluded
      that psychiatric onset of MS may occur in up to 1% of patients, and that in
      previously healthy persons with acute psychotic disorder even the slightest
      neurological abnormality justifies a cranial MRI examination.

PMID- 16631799
TI  - Longitudinal assessment of noninvasive positive pressure ventilation adjustments
      in ALS patients.
AB  - The absence of data guiding optimal titration of noninvasive positive pressure
      ventilation (NIPPV) over time in ALS patients may contribute to the under
      prescribing of NIPPV. We conducted a retrospective, single-center, chart review
      assessment of NIPPV pressure settings used for symptomatic treatment of ALS
      patients to determine NIPPV adjustments, and to compare survival between those
      who were tolerant and intolerant to NIPPV. All subjects were started on nocturnal
      NIPPV at 8 and 3 cm H2O inspiratory and expiratory pressure, respectively. Of the
      18 tolerant subjects identified, 4 (22%) had no NIPPV pressure changes before
      death; 8 (44%), 1 change; 4 (22%), 2 changes; 1 (6%), 3 changes; and 1 (6%), 5
      changes. Most pressure changes occurred during the first year of NIPPV
      initiation. The maximum pressure needed for comfort by any patient in this study
      was 19/5 cm H2O, while 4 (22%) found the original 8/3 cm H2O settings to be
      sufficient until death. Subjects in the tolerant group had better survival, when
      adjusting for age and site of symptom onset (bulbar versus limb), with a hazard
      ratio of 0.23 [95% confidence interval: 0.10, 0.54]. The current data suggest
      that ALS patients who are tolerant to NIPPV typically need at least one upward
      change in pressure settings. Tolerance to relatively low NIPPV inspiratory
      pressures is associated with improved survival.

PMID- 16631800
TI  - Enhanced inflammatory response via activation of NF-kappaB in acute experimental
      diabetic neuropathy subjected to ischemia-reperfusion injury.
AB  - Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in
      diabetic nerves compared to control normoglycemic nerves. The mechanism of this
      excessive susceptibility is unclear. Since reperfusion injury results in an
      inflammatory response, we tested the hypothesis that the diabetic state increases
      the inflammatory cascade. We used an animal model of unilateral ischemia
      reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to
      evaluate the density and localization of mediators of the inflammatory response
      using selective immunolabeling methods (for nuclear factor kappa B (NF-kappaB),
      intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We
      studied a 1-month diabetic group and an age-matched control group (n=6 each). The
      right limb underwent 3 h ischemia at 35 degrees C and 7 days reperfusion. This
      was achieved by ligating the supplying arteries and collaterals to the right
      sciatic-tibial nerve for 3 h, followed by releasing the ties.
      Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF
      kappaB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was
      significantly increased over that of controls subjected to identical IR injury.
      We observed a nearly 2-fold increase in density of NF-kappaB and ICAM-1
      expression in microvessels of diabetic nerve compared with control nerve.
      Extensive infiltration of monocyte macrophages (1C7) was observed in the
      endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS
      48) occurred in the endoneurium of diabetic tibial nerves. This study provides
      evidence for an enhanced inflammatory response in diabetic nerves subjected to IR
      injury apparently via NF-kappaB activation.

PMID- 16631801
TI  - Direction of regeneration waves in grid-based models for forest dynamics.
AB  - Progressing waves of regeneration are observed in forest ecosystems such as
      Shimagare fir forests. The patterns generated by lattice models for forest
      dynamics often show similar waves of disturbance and recovery. This paper
      introduces a method to detect and quantify the directional movement of these
      waves. The method is based only on the disturbance times of the sites and allows
      to distinguish three types of wave patterns: patterns with global direction,
      patterns with local direction, and patterns without direction. We apply this to
      several grid-based models for forest dynamics which are evaluated analytically or
      by simulation. The results reveal a clear distinction of the models which earlier
      studies were not able to detect.

PMID- 16631802
TI  - Modelling the relationship between antibody-dependent enhancement and
      immunological distance with application to dengue.
AB  - When antibodies raised in response to a particular pathogen bind with
      immunologically similar pathogens it may facilitate infection through a
      phenomenon known as antibody-dependent enhancement (ADE). This process occurs
      between the four serotypes of dengue virus and, furthermore, secondary infection
      is a major risk factor in dengue hemorrhagic fever (DHF). Theory has suggested
      that ADE may be responsible for the large immunological distance between dengue
      serotypes. We investigate this hypothesis using an epidemic model for dengue in
      which immunological distance and the strength of immune cross-reaction are
      expressed separately. Cross-enhancement is considered in three alternative forms
      acting on susceptibility, transmission and mortality. Previous models have shown
      that transmission and mortality enhancement can lead to periodicity or chaos. We
      confirm this result for reasonable levels of susceptibility and transmission
      enhancement but not for mortality enhancement. We also show that when the two
      strains have identical basic reproductive numbers no form of enhancement leads to
      competitive exclusion. When the two strains have different basic reproductive
      numbers susceptibility or transmission enhancement allow strains with greater
      immunological similarity to stably coexist but mortality enhancement forces
      strains to be more distinct. All three forms of enhancement can be associated
      with DHF and we conclude that mortality enhancement must be dominant if ADE
      really is responsible for the immunological distance between dengue serotypes.

PMID- 16631804
TI  - Effects of gliclazide beyond metabolic control.
AB  - Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of
      diabetic complications. Recent studies demonstrate that hyperglycemia-induced
      overproduction of superoxide seems the first and key event in the activation of
      all pathways involved in the pathogenesis of diabetic complications. Superoxide
      overproduction is accompanied by increased nitric oxide generation and,
      consequently, formation of the strong oxidant peroxynitrite, and by
      poly(adenosine diphosphate ribose) polymerase activation, which in turn further
      activates the pathways involved in the pathogenesis of diabetic complications.
      This process results in acute endothelial dysfunction and activation of
      inflammation in diabetic blood vessels that, convincingly, contribute to the
      development of diabetic complications. Gliclazide is an oral hypoglycemic agent
      that belongs to the class of sulfonylureas: basic and clinical evidences suggest
      that gliclazide works as an antioxidative drug, independently from its ability to
      reduce hyperglycemia. The availability of a compound that simultaneously
      decreases hyperglycemia, restoring insulin secretion, and inhibits oxidative
      stress produced by high glucose seems to be an interesting therapeutic prospect
      for the prevention of vascular complications of diabetes.

PMID- 16631805
TI  - Sulfonylureas and the risk of myocardial infarction.
AB  - Patients with diabetes mellitus have an increased risk of coronary artery
      diseases such as myocardial infarction. Sulfonylureas are used in the treatment
      of diabetes mellitus and have been linked with adverse cardiovascular effects due
      to an apparent effect on myocardial ischemic preconditioning. Individual
      sulfonylureas differ pharmacologically and may have different effects. Although
      the hypotheses were stimulated by animal studies and experimental studies using
      intermediate end points, data on the possible clinical implications in humans
      remain sparse. However, recent data seem reassuring.

PMID- 16631806
TI  - Long-term efficacy of sulfonylureas: a United Kingdom Prospective Diabetes Study
      perspective.
AB  - The United Kingdom Prospective Diabetes Study shows sulfonylureas to be an
      effective first-line therapy for people with type 2 diabetes mellitus. The
      durability of the glycemic control obtained is dependent on the degree to which
      beta-cell function can be maintained, but sulfonylureas appear neither to
      increase nor to decrease the underlying rate of loss of beta-cell function. As
      sulfonylureas act by enhancing insulin secretion, they are probably best used
      close to the time when diabetes is diagnosed when beta-cell function is at its
      greatest and their utility can be extended by judicious use in combination with
      agents that improve glycemia by different modes of action, including insulin.

PMID- 16631807
TI  - The place of sulfonylureas in the therapy for type 2 diabetes mellitus.
AB  - Sulfonylureas are still largely used for treatment of type 2 diabetic patients,
      and they still occupy a central position in many international therapy
      guidelines. More recently concern has been raised with respect to possible
      adverse effects associated with the use of these agents. Sulfonylureas are,
      indeed, believed to favor the development of hypoglycemia, to accelerate beta
      cell apoptosis and beta-cell exhaustion, and to impair endothelial function with
      increased risk for ischemic complications. However, because of the intrinsic
      pathogenetic heterogeneity of type 2 diabetes, sulfonylureas are likely to remain
      a therapeutic option. Careful choice of a specific sulfonylurea should be made on
      the basis of efficacy, safety, convenience, tissue specificity, and neutrality
      with respect to the beta cell. In this review the advantage:disadvantage ratio of
      available sulfonylureas is analyzed with the purpose of providing a critical
      clinical appraisal of the role of sulfonylureas in the modern treatment of type 2
      diabetes.

PMID- 16631808
TI  - Overcoming the hurdles to achieving glycemic control.
AB  - Several factors influence diabetes control, and many of these can adversely
      affect endeavors to obtain optimal glycemic management. For many patients with
      type 2 diabetes mellitus, the passage of time often results in a loss of
      responsiveness to medication and a greater difficulty in achieving desired target
      levels. Although these observations in part reflect a natural progression of
      diabetes, irrespective of treatment given, it is possible to identify modifiable
      hurdles that can be addressed with better outcome results. Lifestyle measures,
      particularly diet and exercise, remain paramount, whereas other secondary
      confounding factors such as systemic or endocrine disease or other conflicting
      medication need specific therapeutic attention. Most patients with type 2
      diabetes mellitus will require oral hypoglycemic medication and this should be
      prescribed in the simplest, most effective, and safest way. Ensuring that
      patients fully understand treatment objectives is important resulting in better
      compliance with advised treatment. Such compliance can be significantly improved
      by keeping treatment regimens simple. With its novel once-daily formulation,
      gliclazide modified release has been shown to improve adherence to medication and
      result in better glycemic outcome as determined by improved HbA(1c) levels. Its
      benefits in terms of reduced risk of hypoglycemia have been demonstrated in the
      GlUcose control In type 2 diabetes: Diamicron modified release versus glimEpiride
      study.

PMID- 16631809
TI  - Factors affecting outbreaks of high-density Cochlodinium polykrikoides red tides
      in the coastal seawaters around Yeosu and Tongyeong, Korea.
AB  - Red tides caused by the dinoflagellate Cochlodinium polykrikoides occur annually
      in coastal waters of Korea, causing significant damage. A distinguishing
      characteristic of C. polykrikoides red tides is that they develop and persist in
      the open sea, where the water is comparatively clean with little contamination
      from the shore. We examined the causes of and key nutrients involved in high
      density C. polykrikoides red tide outbreaks in the coastal seawaters around Yeosu
      and Tongyeong, Korea. High-density C. polykrikoides red tides occur in the
      coastal areas of Geomo Island, where freshwater flows into the sea after heavy
      rainfall events. Red tides are widespread in years when rainfall is heavy. The
      maximum concentration of C. polykrikoides and the duration of the red tides
      increase with increasing rainfall. Adding nitrogen and Seomjin River water to
      cultures of C. polykrikoides also increases biomass production and cell density
      of C. polykrikoides remarkably increased after heavy rainfall events. The
      occurrence of high concentrations of C. polykrikoides along the shores of Yeosu
      and Tongyeong seems to result from rainfall-initiated inflows of high
      concentrations of nitrate secondarily, after a conducive physical and chemical
      open-water environment has been established for C. polykrikoides to spread
      initially.

PMID- 16631810
TI  - Science, politics and ideology--the Victoria (BC, Canada) sewage issue.

PMID- 16631811
TI  - Species assemblages of Enterococcus indicate potential sources of fecal bacteria
      at a south Florida recreational beach.

PMID- 16631812
TI  - Legal aspects of conserving native oysters in Scotland.
AB  - Native oysters (Ostrea edulis) historically supported valuable fisheries in
      Scotland, but are now absent from areas of former abundance on the east coast and
      occur mainly in isolated populations in west coast sea lochs. The main
      contemporary threat is from unauthorized gathering. In most places, the exclusive
      right to gather is retained by the Crown, as a remnant of the feudal system, but
      in some areas the right has been acquired by individuals or institutions. A
      temporary right to gather oysters may be obtained by permit from the proprietor,
      or through a Several or Regulating Order made under shellfish fisheries
      legislation. The right to gather oysters is separate from ownership of the
      foreshore or sea bed on which they are located. To receive the maximum legal
      protection, oyster beds must be marked out, or the rights to them otherwise
      adequately made known. Wild or formerly-cultivated oyster beds may not meet this
      criterion and, in any case, enforcement is difficult in remote locations. It has
      been proposed that there should be a statutory public right to gather oysters.
      Were this to be created, then strong conservation measures would need to be
      implemented to protect native oysters from eradication by uncontrolled gathering.

PMID- 16631813
TI  - Paralytic shellfish toxin profiles in net phytoplankton samples from Bahia
      Concepcion, Gulf of California, Mexico.

PMID- 16631814
TI  - Polychlorinated biphenyls (PCBs) in sediments of four harbours in Guam.

PMID- 16631815
TI  - Effects of industrial outfalls on tropical macrobenthic sediment communities in
      Reunion Island (Southwest Indian Ocean).
AB  - Temporal changes in the composition of soft bottom macrobenthic assemblages at
      Reunion Island (Southwest Indian Ocean) were studied in the context of a long
      term environmental monitoring programme studying the impacts of effluents of
      industrial sugar cane refineries that are transferred to shallow and deep coastal
      environments by different pathways: surface discharge and deep underground
      injection. Seven stations (between 20 and 160 m depth) were surveyed between 1994
      and 2003 on the industrial zone. One additional station was surveyed on a
      reference site. Spatio-temporal changes in the composition of macrobenthic
      communities were assessed using several diversity indices, ABC curves, MDS and
      associated ANOSIM tests and biotic indices. Among the 171 taxa recorded,
      polychaetes were dominant (89 species), followed by crustaceans and molluscs. The
      analysis of spatial changes in the composition of macrobenthos showed the
      existence of distinct benthic communities along the depth gradient. Temporal
      changes in macrobenthos composition were most prominent at the shallowest
      station. They mainly corresponded to the decline of several initially dominant
      taxa and the increase of the Eunicid polychaete Diopatra cuprea. This station
      further showed increasing macrofaunal abundance, biomass and sediment organic
      content over time, concomitant with decreasing sediment grain sizes. In deeper
      environments, temporal changes were much smaller. Macrofaunal abundance and
      species richness increased progressively, suggesting a moderate impact on benthic
      ecosystems resulting from slight enrichments due to effluents rich in organic
      matter. Our results highlight an original response to disturbance pattern
      involving opportunistic Eunicidae species (D. cuprea) not previously described.
      Moreover, they allow for the comparison of the impact on macrofauna caused by
      industrial effluents exported by two distinct and different pathways in a
      tropical coastal high-energy marine environment.

PMID- 16631816
TI  - Bisexual branching processes in a genetic context: the extinction problem for Y
      linked genes.
AB  - In this paper the inheritance of a Y-linked gene with alleles R and r in a
      population with both females and males is modelled using a two-type bisexual
      branching process. It is assumed that the reproductive distribution associated
      with the R allele can differ from the associated with the r allele and that
      females prefer to mate with a male having the R allele rather than with a male
      with the r allele. Under these assumptions, we provide some conditions for the
      extinction and/or survival of both alleles in the population. These conditions
      depend on the magnitudes of the average number of females and males per mating
      unit. Moreover, the almost sure extinction of the r allele is independent of the
      behaviour of the R allele. On the other hand, the survival of the R allele with
      positive probability may depend strongly on the reproductive behaviour of the
      other allele. Theoretical results are illustrated by means of simulated examples
      and some open problems are proposed to the reader as conjectures.

PMID- 16631817
TI  - Genealogical theory for random mating populations with two sexes.
AB  - Consider a random mating population that has N(m) males and N(f) females in each
      generation. Let us assume that at time 0 a random sample of n copies of a gene is
      taken from this population. Then, for models introduced by Wright [Evolution in
      Mendelian populations, Genetics 16 (1931) 97; Inbreeding and homozygosis, Proc.
      Nat. Acad. Wash. 19 (1933) 420; Evolution and the Genetics of Populations, The
      Theory of Gene Frequencies, vol. II, The University of Chicago, Chicago and
      London, 1969.], it is possible to obtain generalizations of the haploid theory of
      genealogical processes developed by Felsenstein . It is conjectured that these
      hold generally, regardless of the effective population size, if
      n<<min(N(m),N(f)). Generalizations are also proved to hold if n=2.

PMID- 16631818
TI  - Stability and Hopf bifurcation in an approachable haematopoietic stem cells
      model.
AB  - We consider the haematopoietic stem cells model (HSC) with one delay introduced
      by Mackey [M.C. Mackey, Unified hypothesis for the origin of aplastic anemia and
      periodic hematopoiesis, blood 51 (1978) 5; M.C. Mackey, Mathematical models of
      haematopoietic cell replication and control, in: The Art of Mathematical
      Modelling: Case Studies in Ecology, Physiology and Biofluids, H.G. Othmer, F.R.
      Adler, M.A. Lewis, J.C. Dallon (Eds), Prentice-Hall, New York, 1997, p. 149] and
      Andersen and Mackey [L.K. Andersen, M.C. Mackey, Resonance in periodic
      chemotherapy: a case study of acute myelogenous leukemia, J. theor. Biol. 209
      (2001) 113]. There are two possible stationary states in the model. One of them
      is trivial and the second E( *)(tau) depending on the delay is non-trivial . This
      paper investigates the stability of the non-trivial state and occurrence of the
      Hopf bifurcation depending on time delay. We prove the existence and uniqueness
      of a critical values tau(0) and tau of the delay such that E( *)(tau) is
      asymptotically stable for tau<tau(0) and unstable for tau(0)<tau<tau . We show
      that E( *)(tau(0)) is a Hopf bifurcation critical point for an approachable
      model.

PMID- 16631819
TI  - Combinatorial decomposition of an outbreak signature.
AB  - We use mathematically rigorous definitions of epidemiological concepts in order
      to derive a sequential combinatorial model of disease outbreak decomposition. We
      define the idea of a population specific 'disease signature' and use this in
      order to decompose and further understand outbreaks as incidents of spatial and
      temporal spread of disease exposure both in, and across, populations. This allows
      us to differentiate between different disease spread scenarios with a level of
      sensitivity that previous models were unable to provide. This perspective leads
      us to propose a new practical definition for 'outbreak'. In addition, we are able
      to use this model to understand, estimate, and, in some cases, correct for, the
      likely instances of reporting error inherent in disease surveillance. We
      demonstrate our model first with a hypothetical outbreak scenario and then in an
      analysis of suspected outbreaks of waterborne diseases in Massachusetts (MA) in
      1995.

PMID- 16631821
TI  - The precautionary principle and emerging biologic risks: lessons from human
      immunodeficiency virus in blood products.
AB  - In times of crisis, such as during the early 1980s when acquired immune
      deficiency syndrome (AIDS) was first recognized as a threat to the blood supply,
      it can be difficult to find reliable evidence upon which to base appropriate
      public health policies. Unreliable evidence produces substantial scientific
      uncertainty. Yet despite ambiguity and unanswered questions, decisions must be
      made and policy established to protect people's health. The precautionary
      principle provides important guidelines for public health policy decision making
      that are of particular value in times of crisis, such as the emergence of a new
      pathogen: be open and honest about scientific uncertainty; communicate with the
      public; and consider immediate, adaptable policy decisions. Ongoing research into
      the important uncertainties and review of policies in light of the data that
      emerge are crucial to the development of good public policy.

PMID- 16631822
TI  - A patient's perspective on hemophilia.
AB  - People with hemophilia play a central role in partnering with their physicians to
      achieve the best possible clinical and economic outcomes. To make informed
      choices regarding a hemophilia therapy, patients and their caregivers must assess
      four basic areas: safety, purity, cost, and convenience--where safety is the
      number one concern. Access to information, including informed consent on issues
      affecting choice of therapy, treater, regimen, and point of service, ancillary,
      and comprehensive care services, is of fundamental importance when choosing a
      therapy. Hemophilia treaters are often the primary source for information and
      also play a large part in therapy decisions based on possible inhibitor
      formation, patients' lifetime insurance caps, and therapy availability. In order
      to help optimize a patient's outcomes, hemophilia treaters must also periodically
      re-evaluate and modify disease management techniques. Given the devastation of
      the hemophilia community during the worst years of the acquired immune deficiency
      syndrome (AIDS) epidemic, physicians, government agencies, and industry must
      complement policy decisions with medical ethics, psychosocial, and quality-of
      life considerations--and patients must remain vigilant about the safety of their
      therapy. It is imperative that standards of care ensure access to the safest
      therapies available and enable those with hemophilia to live a life only
      minimally disrupted by their disease.

PMID- 16631823
TI  - The need for continuing vigilance: addressing the threat for transmission of
      blood-borne infectious disease.
AB  - As international travel and human encroachment into previously isolated areas
      have increased, so too has the potential for the emergence of new infectious
      diseases. Populations likely to be susceptible to new infectious diseases have
      also increased in size. The past three decades have seen outbreaks of diseases
      caused by parvoviruses, Nipah virus, circoviruses, and prions. Infectious
      pathogens such as these are formidable opponents; they can adapt to new hosts or
      cause variant diseases within new hosts. Many are also resistant to current
      inactivation techniques. In order to prevent or contain outbreaks, pathogens that
      emerge must be identified quickly and efficiently; research and ongoing global
      surveillance are therefore of primary importance. To effectively protect the
      blood supply and blood-based therapies, this research should include
      investigations into improved techniques for detection, screening, and viral
      inactivation, as well as into ways to reduce patient exposure to infectious
      pathogens via therapeutic agents. The proactive devotion of appropriate resources
      to infectious disease containment and prevention prior to an epidemic should be
      perceived as both essential public health policy and cost effective.

PMID- 16631824
TI  - Consideration in hemophilia therapy selection.
AB  - The risk of pathogen transmission via clotting factor therapies has been reduced
      over the last two decades through the development of effective and progressively
      more sensitive pathogen screening and inactivation methods and the introduction
      of recombinant clotting factors for hemophilia, beginning with recombinant factor
      VIII (FVIII) in 1992. However, new understanding about the potential for
      transmission of an emerging infectious agent through blood and blood products has
      renewed concerns about vulnerabilities that remain in plasma-derived and some
      recombinant clotting therapies that still use plasma components during some
      stages of the manufacturing process. In the 1980s, patients with hemophilia
      became "canaries in the coal mine" for human immunodeficiency virus (HIV) and
      hepatitis C virus (HCV) in the blood supply. Moving forward, healthcare providers
      must continue to take a proactive role in educating themselves about new
      information regarding emerging pathogens and develop approaches to discussing
      this risk with their patients as part of their therapy selection process.

PMID- 16631825
TI  - Infectious disease in the blood supply and the public health response.
AB  - The consistent improvements in hemophilia care seen in the years 1960 to 1980
      halted when human immunodeficiency virus (HIV) appeared in the blood supply. In
      the early 1980s, before HIV virulence was fully understood, a complacent blood
      therapy industry and its regulators waffled on an appropriate response. As a
      result, the period between the appearance of HIV and its effective elimination
      from the blood supply was lengthy and many recipients of blood therapies became
      infected, with devastating impact on their quality of life, quality of care, and
      longevity. As the decade wore on, even as they began to better understand the
      threat, industry and public health officials continued to stall, in part because
      development of interventions was costly and cumbersome. In order to protect the
      safety of the blood supply and blood-derived therapies, it must be recognized
      that new pathogens will continue to emerge. Agencies' and companies' decision
      making processes in this regard must therefore be proactive rather than reactive,
      and should preferably implement a formalized risk-management approach. The
      ongoing safety of blood therapies and the blood supply will also depend on
      continued vigilance and research. Finally, the hemophilia community must be
      allowed to play an active and educated role in their own care.

PMID- 16631826
TI  - Tick troponin I-like molecule is a potent inhibitor for angiogenesis.
AB  - This is the first report identifying the anti-angiogenesis saliva molecule of the
      ixodid tick. In our previous study, we identified a troponin I-like molecule
      (HLTnI) of the ixodid hard tick Haemaphysalis longicornis, a vector for various
      pathogens. To investigate its potential inhibitory effects for angiogenesis, we
      expressed and purified recombinant HLTnI in Escherichia coli. In a vascular
      endothelial growth factor (VEGF) competitive angiogenesis assay, the recombinant
      HLTnI significantly inhibited the capillary formation of human vascular
      endothelial cells (HUVEC) in vitro. The inhibition was dose-dependent with an
      IC(50) of 18.95 nM. These results indicated that HLTnI is a potent angiogenesis
      inhibitor.

PMID- 16631827
TI  - L-type calcium channel ligands block nicotine-induced signaling to CREB by
      inhibiting nicotinic receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are inhibited by several drugs that
      are commonly thought to be specific for L-type calcium channels (LTCCs). In
      neurons, LTCCs are activated by nicotine-induced depolarization to engage
      downstream signaling events; however, the role of LTCC drug interactions with
      nAChRs in signaling has not been examined in detail. We investigated the effects
      of LTCC ligands on nAChR currents and downstream signaling in rat superior
      cervical ganglion (SCG) neurons. We found that 10microM nicotine and 40mM K(+)
      both reversibly depolarize SCG neurons to -20mV, sufficient to activate LTCCs and
      downstream signaling, including induction of nuclear phospho-CREB (pCREB); this
      induction was blocked by LTCC antagonists. Interestingly, the effects of LTCC
      antagonists on nicotine-induced signaling to CREB are not mediated by their
      actions on LTCCs, but rather via inhibition of nAChRs, which prevents nicotine
      induced depolarization. We show that this effect is sufficient to block pCREB
      induction in neurons expressing an antagonist-insensitive LTCC. Taken together,
      our data show that, at concentrations typically used to block LTCCs, these
      antagonists inhibit nAChR currents and downstream signaling. These findings serve
      as a caution in attributing a role for LTCCs when using these drugs
      experimentally or therapeutically.

PMID- 16631828
TI  - Insect-antifeedant and antibacterial activity of diterpenoids from species of
      Plectranthus.
AB  - Bio-assay guided fractionation of an acetone extract of leaf material from
      Plectranthus saccatus Benth. resulted in the isolation of a beyerane diterpenoid.
      This compound, characterised by spectroscopic methods as ent-3beta-(3-methyl-2
      butenoyl)oxy-15-beyeren-19-oic acid, showed insect antifeedant activity against
      Spodoptera littoralis. Known quinonoid abietane diterpenoids obtained from new
      sources included a mixture of the (4R,19R) and (4R,19S) diastereoisomers of
      coleon A from P. aff. puberulentus J.K. Morton, coleon A lactone from P.
      puberulentus J.K. Morton, and coleon U and coleon U quinone from P. forsteri
      'Marginatus' Benth. These compounds, and the crude acetone extracts from the leaf
      surfaces of 11 species of Plectranthus, were tested for antifeedant activity
      against S. littoralis, antibacterial activity against Bacillus subtilis and
      Pseudomonas syringae and antifungal activity against Cladosporium herbarum. The
      coleon A mixture showed potent antifeedant activity against S. littoralis,
      whereas coleon U showed the greatest antimicrobial activity.

PMID- 16631829
TI  - In vitro characterization of the homogalacturonan-binding domain of the wall
      associated kinase WAK1 using site-directed mutagenesis.
AB  - Wall-associated kinase 1--WAK1 is a transmembrane protein containing a
      cytoplasmic Ser/Thr kinase domain and an extracellular domain in contact with the
      pectin fraction of the plant cell wall in Arabidopsis thaliana (L.) HEYNH. In a
      previous paper [Decreux, A., Messiaen, J., 2005. Wall-associated kinase WAK1
      interacts with cell wall pectins in a calcium-induced conformation. Plant Cell
      Physiol. 46, 268-278], we showed that a recombinant peptide expressed in yeast
      corresponding to amino acids 67-254 of the extracellular domain of WAK1
      specifically interacts with commercial non-methylesterified homogalacturonic
      acid, purified homogalacturonans from Arabidopsis and oligogalacturonides in a
      calcium-induced conformation. In this report, we used a receptor binding domain
      sequence-based prediction method to identify four putative binding sites in the
      extracellular domain of WAK1, in which cationic amino acids were selected for
      substitution by site-directed mutagenesis. Interaction studies between mutated
      forms of WAK1 and homogalacturonans allowed us to identify and confirm at least
      five specific amino acids involved in the interaction with homogalacturonan
      dimers and multimers. The presence of this homogalacturonan-binding domain within
      the extracellular domain of WAK1 is discussed in terms of cell wall architecture
      and signal transduction.

PMID- 16631830
TI  - Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle
      leucocephala.
AB  - Three C-17 diacetylenic compounds (1-3), one monoterpenoid (4), seven ceramides
      (leucoceramides A-G, 5a-g), six cerebrosides (leucocerebrosides A-F, 6a-f) and
      nine known compounds were isolated from the methanolic extract of Hydrocotyle
      leucocephala. Their structures were established by spectroscopic methods. The
      isolated compounds 1-3, 5a-g, 6a-f and 7 were shown to be active in the
      lipopolysaccharide (LPS) induced cytokine production assay for IL-10, IL-12, and
      TNF-alpha.

PMID- 16631831
TI  - Pregnane, coumarin and lupane derivatives and cytotoxic constituents from
      Helicteres angustifolia.
AB  - 2alpha,7beta,20alpha-Trihydroxy-3beta,21-dimethoxy-5-pregnene (1), 6,7,9alpha
      trihydroxy-3,8,11alpha-trimethylcyclohexo-[d,e]-coumarin (2), 3beta-hydroxy-27
      benzoyloxylup-20(29)-en-28-oic acid (3), and 3beta-hydroxy-27-benzoyloxylup
      20(29)-en-28-oic acid methyl ester (4), along with 24 known compounds were
      isolated and structurally characterized from roots and aerial parts of Helicteres
      angustifolia (Sterculiaceae). In a preliminary bioassay, the two cucurbitacin
      derivatives, cucurbitacin D and J exhibited significant inhibitory activities
      against the growth of both hepatocellular carcinoma BEL-7402 cells and malignant
      melanoma SK-MEL-28 cells in vitro.

PMID- 16631832
TI  - Programmed cell death in vegetative development: apoptosis during the colonial
      life cycle of the ascidian Botryllus schlosseri.
AB  - Programmed cell death (PCD) by apoptosis is a physiological mechanism by which
      cells are eliminated during embryonic and post-embryonic stages of animal life
      cycle. During asexual reproduction, the zooids of colonial ascidians originate
      from an assorted cell population instead of a single zygote, so that we assume
      that regulation of the equilibrium among proliferation, differentiation and cell
      death may follow different pathways in comparison to the embryonic development.
      Here we investigate the presence of apoptotic events throughout the blastogenetic
      life cycle of the colonial ascidian Botryllus schlosseri, by means of terminal
      deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) coupled with
      histochemical and electron microscopy techniques. The occurrence of low levels of
      morphogenetic cell death suggests that, in contrast to what happens during sexual
      development (embryogenesis and metamorphosis), apoptosis does not play a pivotal
      role during asexual propagation in botryllid ascidian. Nevertheless, PCD emerges
      as a key force to regulate homeostasis in adult zooids and to shape and modulate
      the growth of the whole colony.

PMID- 16631833
TI  - Expression of alpha V integrin is modulated by Epstein-Barr virus nuclear antigen
      3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and
      Sp1 transcription factors.
AB  - Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the
      world's population. It is associated with a number of human lymphoid and
      epithelial tumors and lymphoproliferative diseases in immunocompromised patients.
      A subset of latent EBV antigens is required for immortalization of primary B
      lymphocytes. The metastatic suppressor Nm23-H1 which is downregulated in human
      invasive breast carcinoma reduces the migration and metastatic activity of breast
      carcinoma cells when expressed from a heterologous promoter. Interestingly, the
      EBV nuclear antigen 3C (EBNA3C) reverses these activities of Nm23-H1. The alpha V
      integrins recognize a variety of ligands for signaling and are involved in cell
      migration and proliferation and also serve as major receptors for extracellular
      matrix-mediated cell adhesion and migration. The goal of this study was to
      determine if Nm23-H1 and EBNA3C can modulate alpha V integrin expression and
      downstream activities. The results of our studies indicate that Nm23-H1
      downregulates alpha V intregrin expression in a dose responsive manner. In
      contrast, EBNA3C can upregulate alpha V integrin expression. Furthermore, the
      study showed that the association of the Sp1 and GATA transcription factors with
      Nm23-H1 is required for modulation of the alpha V integrin activity. Thus, these
      results suggest a direct correlation between the alpha V integrin expression and
      the interaction of Nm23-H1 with EBNA3C.

PMID- 16631834
TI  - Root canal irrigants.
AB  - Local wound debridement in the diseased pulp space is the main step in root canal
      treatment to prevent the tooth from being a source of infection. In this review
      article, the specifics of the pulpal microenvironment and the resulting
      requirements for irrigating solutions are spelled out. Sodium hypochlorite
      solutions are recommended as the main irrigants. This is because of their broad
      antimicrobial spectrum as well as their unique capacity to dissolve necrotic
      tissue remnants. Chemical and toxicological concerns related to their use are
      discussed, including different approaches to enhance local efficacy without
      increasing the caustic potential. In addition, chelating solutions are
      recommended as adjunct irrigants to prevent the formation of a smear layer and/or
      remove it before filling the root canal system. Based on the actions and
      interactions of currently available solutions, a clinical irrigating regimen is
      proposed. Furthermore, some technical aspects of irrigating the root canal system
      are discussed, and recent trends are critically inspected.

PMID- 16631835
TI  - Endodontic treatment outcome: survey of oral health care professionals.
AB  - This study assessed the opinion of oral health care professionals regarding the
      predictability of initial endodontic treatment, expected long-term outcome and
      the importance of placing a coronal coverage after completion of treatment. An
      eight-item questionnaire was distributed among oral health care professionals.
      There were 49% of participants who responded that the expected retention rate of
      teeth 5 to 10 yr after endodontic treatment was more than 90%, whereas 44%
      responded that such retention rate was between 70 to 80%. The majority of the
      participants also responded that the need for additional treatment, such as
      retreatment, apical surgery or extraction, was expected to occur within the first
      3 yr after endodontic treatment if initial treatment has failed. About 87% of
      participants responded that placing coronal coverage after completion of
      endodontic treatment in premolars and molars was very important for long-term
      tooth retention and 92% responded that overall, endodontic treatment was a
      predictable procedure with long-term tooth retention rate. Statistically
      significant associations were found between years of experience and expected rate
      of retention for both the total group of respondents (p < 0.001) and for general
      practitioners when examined separately (p < 0.002). Statistically significant
      associations were only found for general practitioners between years of
      experience and their responses regarding the need for additional treatment (p <
      0.05) and overall predictability of endodontic treatment (p < 0.02). A trend was
      found between the professionals' years of experience and their opinion regarding
      the importance of coronal coverage. Of the group who had more than 20 yr of
      experience, about 87% considered coronal coverage to be very important for long
      term tooth retention. In conclusion, it appears that most clinicians
      participating in this study consider endodontic therapy to be a predictable
      procedure with long-term tooth retention rate. Their opinions also reflect the
      variations that currently exist in the literature regarding the reported outcome
      of endodontic treatment.

PMID- 16631836
TI  - Effects of Nd:YAG laser pulpotomy on human primary molars.
AB  - The purpose of this study was to compare the effects of Nd:YAG laser pulpotomy to
      formocresol pulpotomy on human primary teeth. Patients with a primary tooth that
      required pulpotomy because of pulpal exposure to caries, were selected for this
      study. After removal of coronal pulpal tissue, Nd:YAG laser at 2 W, 20 Hz, 100 mJ
      or a 1:5 dilution of formocresol was introduced into the canal orifice for
      complete hemostasis. IRM paste was then placed over the pulp stump, and the tooth
      was restored either with composite resin or stainless steel crown. Sixty-eight
      teeth were treated with Nd:YAG laser and followed up for 6 to 64 months. Clinical
      success was achieved in 66 out of the 68 teeth (97 %), and 94.1 % were
      radiographically successful. In the control group, 69 primary molars were treated
      with formocresol and followed up for 9 to 66 months; 85.5 and 78.3% achieved
      clinical and radiographic success, respectively. The success rate of Nd:YAG laser
      pulpotomy was significantly higher than that of formocresol pulpotomy. The
      permanent successors of the laser-treated teeth erupted without any
      complications.

PMID- 16631837
TI  - Upregulation of basic fibroblast growth factor in human periapical lesions.
AB  - Basic fibroblast growth factor is one of a class of heparin-binding growth
      factors that stimulates endothelial cell proliferation and migration in vitro and
      angiogenesis in vivo. The purpose of this study was to investigate the expression
      of basic fibroblast growth factor in chronic periapical lesions of endodontic
      origin. Ten chronic inflammatory periapical lesions were examined using
      immunohistochemical staining. The experimental control group consisted of four
      specimens of uninflamed periodontal ligament tissue. Two independent observers
      graded the staining intensity for basic fibroblast growth factor. An
      immunopositive, cytoplasmic, and nuclear reaction for basic fibroblast growth
      factor, with varying degrees of upregulation was observed in all 10 chronic
      periapical lesions. We speculate that the formation of granulation tissue and the
      activation of epithelial cell rests in chronical apical lesions might be
      associated with a local rise in the tissue level of basic fibroblast growth
      factor. Therefore, this growth factor could play an important role in the
      pathogenesis of chronic apical periodontitis and periapical cysts.

PMID- 16631838
TI  - Retrospective evaluation of surgical endodontic treatment: traditional versus
      modern technique.
AB  - The aim of this retrospective study was to compare the outcome of surgical
      endodontic treatment preformed using the traditional versus modern techniques.
      There were 110 patients who were treated by surgical endodontic treatment between
      2000 and 2002 and evaluated from their dental charts. The surgical endodontic
      treatment was preformed using a traditional or modern technique. The traditional
      technique included root-end resection with a 45 degrees bevel angle, and
      retrograde preparation using a carbide round bur. The modern technique included
      root-end resection with minimal or no bevel, and retrograde preparation using
      ultrasonic retro-tips with the aid of a dental operating microscope. The
      retrograde filling material for both techniques was intermediate restorative
      material. There were 71 patients with 88 treated teeth that were compatible with
      the inclusion criteria. Complete healing rate for the teeth treated with the
      modern technique (91.1%) was significantly higher than that for teeth treated
      using the traditional technique (44.2%) (p < 0.0001). In the traditional
      technique a significant (p = 0.032) negative influence of the tooth type was
      found. Modern surgical endodontic treatment using operative microscope and
      ultrasonic tips significantly improves the outcome of the therapy compared to the
      traditional technique.

PMID- 16631839
TI  - Determination of the minimum instrumentation size for penetration of irrigants to
      the apical third of root canal systems.
AB  - The purpose of this study was to determine the minimum instrumentation size
      required for the effective penetration of irrigants and elimination of debris and
      smear layer from the apical third of the root canals. The mesiobuccal canals of
      40 freshly extracted human mandibular first molar teeth were instrumented using
      the crown-down technique. The teeth were divided into four test groups according
      to the size of their Master Apical File (#20, #25, #30, #35), and two control
      groups. After final irrigation, the removal of debris and smear layer from the
      apical third of root canals was determined under a scanning electron microscope.
      The data was analyzed using Kruskal-Wallis and Mann-Whitney tests. Based on the
      results, it appears that the minimum instrumentation size needed for penetration
      of irrigants to the apical third of the root canal is a #30 file.

PMID- 16631840
TI  - Effect of blood contamination on retention characteristics of MTA when mixed with
      different liquids.
AB  - Simulated furcation perforations were repaired with and without blood
      contamination utilizing tooth-colored mineral trioxide aggregrate (MTA) mixed
      with either MTA liquid (sterile water), lidocaine, or saline. Samples underwent
      Instron testing at either 24 or 72 hours and at 7 days. Data were analyzed using
      a 3-way ANOVA and post-hoc testing using Turkey's true test for significance. All
      of the 72-hour samples displayed significantly greater resistance to displacement
      than the 24-hour samples. All of the 7-day samples displayed significantly
      greater resistance to displacement than the 24-hour and 72-hour samples. Non
      contaminated samples displayed significantly greater resistance to displacement
      than their blood-contaminated counterparts at 7 days. Non-contaminated samples
      mixed with sterile water, lidocaine, or saline performed similarly at all time
      periods. Allowing tooth-colored MTA to set undisturbed for 72 hours or longer
      prior to placement of a coronal restoration may decrease the chance of MTA
      displacement in furcation perforation repairs.

PMID- 16631841
TI  - Elemental analysis of crystal precipitate from gray and white MTA.
AB  - Crystal growth and elemental dissolution characteristics of gray Mineral Trioxide
      Aggregate (GMTA), white MTA (WMTA), and an experimental material, Dentalcrete,
      were compared. For part A, comparing amount and composition of surface crystal
      growth, twelve cylinders of each material were suspended in Phosphate Buffered
      Saline (PBS) solution without Ca. The crystals were analyzed by Scanning Electron
      Microscopy (SEM), X-ray Diffraction (XRD), and Inductively Coupled Plasma--Atomic
      Emission Spectroscopy (ICP-AES). For part B, three cylinders of each material
      were suspended in distilled, deionized water. The water was analyzed by ICP-AES
      for Ca content at 24 h, 72 h, and 5, 7, 10, and 14 days. Data were analyzed using
      one-way ANOVA and Tukey test. Both MTA materials released more Ca initially,
      followed by a decline and then rise in elution. GMTA produced the most surface
      crystal, which may be clinically significant. The crystals on GMTA and WMTA were
      chemically and structurally similar to hydroxyapatite (HA).

PMID- 16631842
TI  - Is an oxygen inhibited layer required for bonding of resin-coated gutta-percha to
      a methacrylate-based root canal sealer?
AB  - Removal of the oxygen inhibition layer from the surface of resin-coated gutta
      percha cones during packaging has been hypothesized for their weak adhesion to a
      methacrylate-based root canal sealer, resulting in their frequent delamination
      from the sealer after root canal obturation. This study examined the feasibility
      of creating oxygen inhibition layers on resin-coated gutta-percha cones via the
      adjunctive application of a dual-cured dentin adhesive just before bonding.
      Composite cylinders were bonded with EndoREZ to flat, resin-coated gutta-percha
      disks and similar disks that were post-treated with Prime&Bond NT Dual Cure
      adhesive and stressed to failure using a modified microshear testing design.
      Although shear strengths for both groups were relatively low, a 5-fold increase
      in shear strength was observed after adhesive application, with complex
      interfacial failures instead of complete sealer delamination from the resin
      coating. In-situ dentin adhesive application appears to have merits in enhancing
      the coupling of resin-coated gutta-percha to methacrylate sealers.

PMID- 16631843
TI  - The effect of exposure to irrigant solutions on apical dentin biofilms in vitro.
AB  - This study assessed the effectiveness of different concentrations of sodium
      hypochlorite (NaOCl), 2% chlorhexidine (CHX) (Vista Dental Products, Racine, WI),
      and BioPure MTAD (Dentsply Endodontics-Tulsa Dental, Tulsa, OK). Intracanal
      contents were collected from 10 patients diagnosed with chronic apical
      periodontitis. The samples were cultured on hemisections of root apices to
      generate a polymicrobial biofilm. Each biofilm was separately immersed in 6%
      NaOCl, 3% NaOCl, 1% NaOCl, 2% CHX, 1% NaOCl followed by BioPure MTAD, and sterile
      phosphate buffered solution (PBS). SEM analysis showed 6% NaOCl and 3% NaOCl were
      capable of disrupting and removing the biofilm; 1% NaOCl and 1% NaOCl followed by
      MTAD were capable of disrupting the biofilm, but not eliminating bacteria; 2% CHX
      was not capable of disrupting the biofilm. Viable bacteria could not be cultured
      from specimens exposed to 6% NaOCl, 2 % CHX, or 1% NaOCl followed by BioPure
      MTAD. These results indicate that 6% NaOCl was the only irrigant capable of both
      rendering bacteria nonviable and physically removing the biofilm.

PMID- 16631844
TI  - In vitro infrared thermographic assessment of root surface temperatures generated
      by high-temperature thermoplasticized injectable gutta-percha obturation
      technique.
AB  - The aim of this in vitro study was to measure the temperature rises on the outer
      surface of roots produced by high-temperature thermoplasticized injectable gutta
      percha technique. Thirty extracted human teeth with a single canal (15 maxillary
      central incisors and 15 mandibular central incisors) were used in this study.
      After root canal cleaning and shaping, the teeth were obturated with the injected
      gutta-percha heated to 160 degrees C (Obtura II). Temperature changes on the
      whole mesial outer surface of the roots was measured using an infrared thermal
      imaging camera. It showed that the use of gutta-percha heated to 160 degrees C to
      fill the maxillary central incisors and mandibular central incisors resulted in
      the rises of the root surface temperature by 8.5 degrees C and 22.1 degrees C,
      respectively. In conclusion, the injection of the gutta-percha heated to 160
      degrees C into the root canal of maxillary central incisors produces temperature
      on the outer root surfaces below the theoretical critical level and, therefore,
      should not cause damage to supporting periradicular tissues. The injection of
      gutta-percha into the root canal space of the mandibular central incisors in
      vitro, resulted in an elevation of the root surface temperature by more than 10
      degrees C.

PMID- 16631845
TI  - Role of free radicals and metal ions in direct current-induced cytotoxicity.
AB  - The purpose of this study was to investigate the mechanism of direct current (DC)
      induced cytotoxicity. To test the working hypothesis that electrolysis products
      are responsible for the DC-induced cytotoxicity, the cytotoxic effects between
      the direct and indirect DC treatment against human polymorphonuclear cells (PMNs)
      was compared. The indirect DC treatment (treatment with the culture medium
      exposed to DC) was comparable in cytotoxicity to the direct DC treatment,
      suggesting that electrolysis products have an important role in DC-induced
      cytotoxicity. Metal ions released from different electrodes into the culture
      medium were quantified by the inductively coupled plasma-mass spectroscopy.
      Higher concentrations of Ag, Zn, and Ni and chromium were released from Ag, Zn,
      and stainless steel (St) electrodes, respectively, whereas much lower
      concentrations of Ni and Ti were released from Ni-Ti electrode. Further, electron
      spin resonance spectroscopy with spin-trapping agent showed that the direct
      current with the following metal electrodes generated alkoxyl radical (St and Ni
      Ti electrodes), hydrogen radical (Ag and Au electrodes), and both carbon and
      alkoxyl radicals (Zn electrode), respectively. These results suggest that free
      radicals and metal ions released from electrodes contribute to the cytotoxicity
      of DC treatment used for iontophoresis.

PMID- 16631846
TI  - Improving the quality of the quartz fiber postcore bond using sodium ethoxide
      etching and combined silane/adhesive coupling.
AB  - The influence of different silane/dentin adhesives on the microtensile bond
      strengths of a hybrid composite to sodium ethoxide-etched quartz fiber posts was
      investigated. A prehydrolyzed silane was applied without an adhesive and compared
      to two-component systems in which hydrolysis of the silane occurred after mixing
      with the acidic monomer present in the dentin adhesives. Nanoleakage along
      post/core interfaces was examined after silver nitrate tracer penetration using
      scanning electron microscopy. Higher interfacial strengths and more uniform
      adaptation between the etched fiber post surface and the composite core were
      recorded after post treatment with silane/adhesive couplings. The combination of
      silane with two-step self-etch adhesives improves the chemical retention of
      composites around etched fiber posts with minimal nanoleakage. Although the one
      step self-etching adhesive/silane combination enhances post adhesion, the
      extensive nanoleakage provides channels for rapid water sorption that may
      expedite hydrolytic degradation of the post/core interface.

PMID- 16631847
TI  - Contamination of tooth-colored mineral trioxide aggregate used as a root-end
      filling material: a bacterial leakage study.
AB  - This experiment investigated the ability of tooth-colored mineral trioxide
      aggregate (MTA) to maintain an apical seal in the presence of bacteria when
      contaminated with blood, saline or saliva. Ninety extracted human teeth with
      single canals were randomly placed into six groups of 15. Canals were prepared to
      size 50. The apical 3 mm of each root was removed and 3 mm root-end preparations
      were made with a #329 bur. Root-end preparations in groups 1 through 3 were
      filled with MTA after contamination with blood, saline, or saliva, respectively.
      In group 4, uncontaminated root-end preparations were filled with MTA. Groups 5
      and 6 served as negative and positive controls. A tube/tooth assembly was
      utilized to suspend each root end in Trypticase Soy Broth (TSB). The access
      chambers were filled with Staphylococcus epidermidis. Positive growth over thirty
      days was demonstrated by turbidity of the TSB. Vitek analysis was used to confirm
      the presence of S. epidermidis in the positive samples. Data evaluation consisted
      of a chi(2) analysis (p < 0.05). Although all experimental groups demonstrated
      leakage, tooth-colored MTA contaminated with saliva (group 3) leaked
      significantly more than the uncontaminated tooth-colored MTA (group 4) (p =
      0.028).

PMID- 16631848
TI  - A quantitative comparison of the fill density of MTA produced by two placement
      techniques.
AB  - This study compared the fill density of mineral trioxide aggregate (MTA) produced
      by hand condensation with that produced by hand condensation with indirect
      ultrasonic (US) activation. Sixty acrylic blocks with straight or curved canals
      were instrumented to an apical size 45, and weighed with a digital electronic
      balance. In 30 randomly chosen specimens, the canal was filled with MTA by hand
      condensation and weighed. The MTA was removed; the canal was rinsed and dried,
      and refilled using hand condensation with indirect US activation. In the other 30
      specimens, the procedure was carried out identically but in reverse order. The
      blocks were then reweighed. The weight of the MTA fill produced by the two
      placement methods in the two canal configurations was analyzed by a two-way
      ANOVA. Hand condensation with indirect US activation resulted in an MTA fill that
      was statistically significantly heavier, and thus denser, than that accomplished
      by hand condensation alone in both curved and straight canals (p < 0.0001).

PMID- 16631849
TI  - Interaction between EDTA and sodium hypochlorite: a nuclear magnetic resonance
      analysis.
AB  - Recent studies detected erosion of the dentinal walls following the use of EDTA
      as a final flush. Several authors have studied degradation of EDTA and it appears
      to be caused by an oxidation reaction. The objective of this paper was to verify
      through nuclear magnetic resonance (NMR) analysis if the oxidizing property of
      sodium hypochlorite inactivates EDTA. Solutions of sodium hypochlorite and EDTA
      were analyzed. EDTA tracing and the appearance of new signals indicative of by
      products of the reaction, were studied at different time intervals with a NMR
      analysis. The tracings of NMR analysis confirmed that the reaction between sodium
      hypochlorite and EDTA lead to a very slow but progressive degradation of this
      compound. Mindful of the limitations of an in vitro study, the results of this
      study nevertheless demonstrated that a final flush with sodium hypochlorite
      cannot limit the chelating effects of EDTA in a clinically realistic time period.

PMID- 16631850
TI  - Ultramorphological and histochemical changes after ER,CR:YSGG laser irradiation
      and two different irrigation regimes.
AB  - The purpose of this study was to evaluate the ultramorphological and chemical
      changes in Er,Cr:YSGG laser-treated radicular dentin in comparison with two
      different irrigation regimes. Extracted human premolars were assigned into three
      experimental groups. Group 1: After each file size, root canals were irrigated
      with 5.25% NaOCL, followed by a final irrigation with 5.25% NaOCL. Group 2: At
      each file size, biomechanical preparation was performed in conjunction with Rc
      Prep, followed by 5.25% NaOCL irrigation; and 5.25% NaOCL for the final flush.
      Group 3: 5.25% NaOCL was used after each file size, followed by Er,Cr:YSGG laser
      irradiation; and a final flush with 5.25% NaOCL. Scanning electron microscopic
      (SEM) evaluations revealed failure of smear removal in NaOCL-irrigated specimens.
      RC-Prep + NaOCL-treated dentin revealed moderate-to-total presence of the smear
      layer with distinct areas of exposed collagen. Er,Cr:YSGG laser irradiation of
      radicular dentin also resulted in partial or total removal of the smear
      associated with a few small regions of thermal injury, including carbonization
      and partial melting. Energy dispersive X-ray analysis (SEM-EDX) showed no
      significant difference between the Ca/P ratios of the test groups, suggesting
      absence of changes at the molecular level.

PMID- 16631851
TI  - Efficacy of different rotary instruments for gutta-percha removal in root canal
      retreatment.
AB  - The purpose of this study was to evaluate the efficiency of FlexMaster, ProTaper,
      and RaCe rotary instruments compared with Hedstrom files for removal of gutta
      percha during retreatment. Sixty mandibular premolars with one single straight
      canal were instrumented with K-type files and filled using cold lateral
      compaction and sealer. The teeth were randomly divided into four groups of 15
      specimens each. After repreparation with Gates Glidden burs and the test
      instruments the specimens were cleared. The area of remaining gutta-percha/sealer
      on the root canal wall was measured from two directions. The RaCe group showed
      significantly less residual obturation material than FlexMaster and Hedstrom
      group (p < 0.05; closed test procedure). There was no difference between ProTaper
      and all other instruments (p > 0.05). ProTaper and RaCe instruments required
      significantly less time for retreatment than FlexMaster and Hedstrom files (p <
      0.05). One RaCe file, two ProTaper, and two FlexMaster instruments separated.
      RaCe cleaned obturated canals more effectively than hand files and FlexMaster
      files.

PMID- 16631852
TI  - Ultrastructure of intraradicular dentin after irrigation with BioPure MTAD. II.
      The consequence of obturation with an epoxy resin-based sealer.
AB  - In addition to an initial report on the creation of thick demineralized collagen
      matrices in root dentin that were irrigated with BioPure MTAD or EDTA as final
      rinses for 5 minutes, this study examined the effect of a 2-minute irrigation
      time of these final irrigants on the extent of demineralization of intact
      intraradicular dentin and on interfacial nanoleakage after obturation with AH
      Plus and gutta-percha using warm vertical compaction. Transmission electron
      microscopy confirmed that the reduction in irrigation time did not compromise the
      smear layer removing capacity of these two irrigants when 1.3% NaOCl was employed
      as the initial rinse. BioPure MTAD created 5 to 6 microm thick demineralized
      dentin matrices, while 17% EDTA produced 1 to 2 microm thick matrices that were
      suboptimally infiltrated by the epoxy resin-based sealer, as manifested by the
      occurrence of silver tracer deposits within the hybrid layers.

PMID- 16631853
TI  - Nonsurgical endodontic treatment of a two-rooted maxillary central incisor.
AB  - This case report presents an uncommon case of a two-rooted maxillary central
      incisor with a periapical radiolucent lesion. A 17-yr-old female patient was
      referred for dental consultation after a motorcycle accident. The maxillary left
      central incisor had a bifurcated root that was confirmed by radiographs taken at
      different angles. Nonsurgical endodontic therapy was performed. At the 1 yr
      recall examination, the tooth was asymptomatic and the radiograph showed that the
      periapical radiolucent lesion had healed.

PMID- 16631854
TI  - Management of the perforations due to miniplate application.
AB  - Microdimensioned osteosynthesis using miniplates has been common practice in
      maxillofacial surgery. However, tooth injury during the application of the
      miniplates have been reported in few papers. In this case, a 32-yr-old female
      patient, whose two teeth were necrosed because of the perforation during screw
      insertion was presented. The reason of the perforations during the rigid internal
      fixation was the lack of radiographic assessment because of the pregnancy.
      Maxillary right first premolar and maxillary left canine were perforated and
      necrosed because of the screw insertion. The necrosed teeth were detected 1 yr
      after the rigid internal fixation. The root canals of nonvital teeth were filed
      using step-down approach. Cold lateral condensation of gutta-percha was used to
      fill the canals. Six-month recall visits were scheduled and there was no problem
      after 2-yr follow-up period.

PMID- 16631855
TI  - Interaction of trace elements in acid mine drainage solution with humic acid.
AB  - The release of metal ions from a coal mining tailing area, Lamphun, Northern
      Thailand, is studied by leaching tests. Considerable amounts of Mn, Fe, Al, Ni
      and Co are dissolved in both simulated rain water (pH 4) and 10 mg L(-1) humic
      acid (HA) solution (Aldrich humic acid, pH 7). Due to the presence of oxidizing
      pyrite and sulfide minerals, the pH in both leachates decreases down to
      approximately 3 combined with high sulfate concentrations typical to acid mine
      drainage (AMD) water composition. Interaction of the acidic leachates upon mixing
      with ground- and surface water containing natural organic matter is simulated by
      subsequent dilution (1:100; 1:200; 1:300; 1:500) with a 10 mg L(-1) HA solution
      (ionic strength: 10(-3) mol L(-1)). Combining asymmetric flow field-flow
      fractionation (AsFlFFF) with UV/Vis and ICP-MS detection allows for the
      investigation of metal ion interaction with HA colloid and colloid size
      evolution. Formation of colloid aggregates is observed by filtration and AsFlFFF
      depending on the degree of the dilution. While the average HA size is initially
      found to be 2 nm, metal-HA complexes are always found to be larger. Such
      observation is attributed to a metal induced HA agglomeration, which is found
      even at low coverage of HA functional groups with metal ions. Increasing the
      metal ion to HA ratio, the HA bound metal ions and the HA entities are growing in
      size from <3 to >450 nm. At high metal ion to HA ratios, precipitation of FeOOH
      phases and HA agglomeration due to colloid charge neutralization by complete
      saturation of HA complexing sites are responsible for the fact that most of Fe
      and Al precipitate and are found in a size fraction >450 nm. In the more diluted
      solutions, HA is more relevant as a carrier for metal ion mobilization.

PMID- 16631856
TI  - Treatability of chloro-s-triazines by conventional drinking water treatment
      technologies.
AB  - Recent research shows that herbicide atrazine (ATZ), simazine (SIM), and
      propazine (PROP), as well as their three chlorinated degrades-desethylatrazine
      (DEA), deisopropylatrazine (DIA), and didealkylatrazine (DDA)-may cause a common
      toxic effect in terms of endocrine disruption. The US Environmental Protection
      Agency (EPA) is currently considering a regulatory trigger based on the sum of
      these concentrations of these six chloro-s-triazines. While limited removal data
      exists for the parent compounds, little information is available for the degrades
      formed biologically and/or chemically in the environment and in the treatment
      plants. It is therefore critical to assess the removal efficiency in a typical
      water plant of the parent herbicides, as well as the daughter products. In this
      work, conventional drinking water treatment technologies were evaluated under
      typical water treatment plant conditions to determine their effectiveness in
      removing six chloro-s-triazines: ATZ, SIM, PROP, DEA, DIA, and DDA. Experiments
      were conducted using synthetic solutions prepared by spiking both distilled water
      and Missouri River water with the study compounds. Two powder activated carbons
      (PAC)--Calgon WPH and Norit HDB-were shown to be partially effective in removing
      the studied chloro-s-triazines. Ozonation efficiency varied, depending on
      different water sources, with respect to the removal of atrazine and
      didealkylatrazine. Coagulation/flocculation/sedimentation with alum and iron
      salts, excess lime/soda ash softening, and disinfection by free chlorine were all
      ineffective methods for removing chloro-s-triazines. It appears that chloro-s
      triazine compounds are not readily removed by most conventional drinking water
      treatment processes, with the exception of use of activated carbon.

PMID- 16631857
TI  - HIV prevention policy needs an urgent cure.

PMID- 16631858
TI  - Reviving research into psychedelic drugs.

PMID- 16631859
TI  - Urgent changes needed for authorisation of phase I trials.

PMID- 16631860
TI  - Bladder tissue-engineering: a new practical solution?

PMID- 16631861
TI  - COPD: the dangerous underestimate of 15%.

PMID- 16631862
TI  - When pharmacists refuse to dispense prescriptions.

PMID- 16631863
TI  - Adolescent sexual health? Let us get real!

PMID- 16631864
TI  - Do truth commissions heal? The East Timor experience.

PMID- 16631865
TI  - Beyond borders: public-health surveillance.

PMID- 16631867
TI  - Cuttings.

PMID- 16631868
TI  - John Martin.

PMID- 16631869
TI  - Recent developments and controversies in depression.

PMID- 16631870
TI  - Recent developments and controversies in depression.

PMID- 16631871
TI  - Recent developments and controversies in depression.

PMID- 16631872
TI  - Recent developments and controversies in depression.

PMID- 16631873
TI  - Recent developments and controversies in depression.

PMID- 16631874
TI  - Folate supplementation and cardiovascular disease.

PMID- 16631875
TI  - Folate supplementation and cardiovascular disease.

PMID- 16631877
TI  - Preparing for pandemic influenza.

PMID- 16631878
TI  - Bird flu prevention.

PMID- 16631879
TI  - Tissue-engineered autologous bladders for patients needing cystoplasty.
AB  - BACKGROUND: Patients with end-stage bladder disease can be treated with
      cystoplasty using gastrointestinal segments. The presence of such segments in the
      urinary tract has been associated with many complications. We explored an
      alternative approach using autologous engineered bladder tissues for
      reconstruction. METHODS: Seven patients with myelomeningocele, aged 4-19 years,
      with high-pressure or poorly compliant bladders, were identified as candidates
      for cystoplasty. A bladder biopsy was obtained from each patient. Urothelial and
      muscle cells were grown in culture, and seeded on a biodegradable bladder-shaped
      scaffold made of collagen, or a composite of collagen and polyglycolic acid.
      About 7 weeks after the biopsy, the autologous engineered bladder constructs were
      used for reconstruction and implanted either with or without an omental wrap.
      Serial urodynamics, cystograms, ultrasounds, bladder biopsies, and serum analyses
      were done. RESULTS: Follow-up range was 22-61 months (mean 46 months). Post
      operatively, the mean bladder leak point pressure decrease at capacity, and the
      volume and compliance increase was greatest in the composite engineered bladders
      with an omental wrap (56%, 1.58-fold, and 2.79-fold, respectively). Bowel
      function returned promptly after surgery. No metabolic consequences were noted,
      urinary calculi did not form, mucus production was normal, and renal function was
      preserved. The engineered bladder biopsies showed an adequate structural
      architecture and phenotype. CONCLUSIONS: Engineered bladder tissues, created with
      autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in
      omentum after implantation, can be used in patients who need cystoplasty.

PMID- 16631880
TI  - Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine
      against human papillomavirus types 16 and 18: follow-up from a randomised control
      trial.
AB  - BACKGROUND: Effective vaccination against HPV 16 and HPV 18 to prevent cervical
      cancer will require a high level of sustained protection against infection and
      precancerous lesions. Our aim was to assess the long-term efficacy,
      immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04
      vaccine against incident and persistent infection with HPV 16 and HPV 18 and
      their associated cytological and histological outcomes. METHODS: We did a follow
      up study of our multicentre, double-blind, randomised, placebo-controlled trial
      reported in 2004. We included women who originally received all three doses of
      bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or placebo
      (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical
      cytology assessments. We also studied the long-term immunogenicity and safety of
      the vaccine. FINDINGS: More than 98% seropositivity was maintained for HPV-16/18
      antibodies during the extended follow-up phase. We noted significant vaccine
      efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96.9% (95% CI
      81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month
      definition, 100% (33.6-100). In a combined analysis of the initial efficacy and
      extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical
      intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted
      broad protection against cytohistological outcomes beyond that anticipated for
      HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The
      vaccine has a good long-term safety profile. INTERPRETATION: Up to 4.5 years, the
      HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and
      induces a high degree of protection against HPV-16/18 infection and associated
      cervical lesions. There is also evidence of cross protection.

PMID- 16631881
TI  - Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide
      treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a
      prospective cohort study.
AB  - BACKGROUND: HIV-1 and malaria are common infections in Africa, and cause
      substantial morbidity and mortality. HIV infection has been associated with an
      increased incidence of malaria, and more severe disease. Our aim was to assess
      the effect of antiretroviral treatment (ART) on the frequency of clinical malaria
      in people with HIV, and to measure the additive effects of co-trimoxazole
      (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated
      bednets. METHODS: In 2001, we enrolled 466 HIV-infected individuals aged 18 years
      or older in Uganda in a prospective cohort study that provided co-trimoxazole
      prophylaxis to 399 participants after 5 months of no intervention. In 2003, we
      enrolled 138 survivors from the initial study, and 897 new participants from the
      same community, to take antiretroviral therapy (ART) in addition to co
      trimoxazole prophylaxis. The ART was in most cases a combination of stavudine,
      lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants
      insecticide-treated bednets. Households were visited weekly by study staff to
      record fever, illness, or death in the preceding 7 days. In cases of reported
      fever in the previous 2 days, we took blood to test for malaria parasites. We
      compared the frequency of clinical malaria, adjusting for CD4-cell count, age,
      sex, and season. FINDINGS: 1035 individuals were given co-trimoxazole and ART
      (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL);
      985 of these, plus four new participants, received co-trimoxazole, ART, and
      bednets. There were 166 cases of clinical malaria in the study. Compared with a
      baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole
      prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted
      incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with
      3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and
      bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria
      incidence was significantly lower during ART and co-trimoxazole than during co
      trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION: A
      combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated
      bednets substantially reduced the frequency of malaria in adults with HIV.

PMID- 16631882
TI  - Mild cognitive impairment.
AB  - Mild cognitive impairment is a syndrome defined as cognitive decline greater than
      expected for an individual's age and education level but that does not interfere
      notably with activities of daily life. Prevalence in population-based
      epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some
      people with mild cognitive impairment seem to remain stable or return to normal
      over time, but more than half progress to dementia within 5 years. Mild cognitive
      impairment can thus be regarded as a risk state for dementia, and its
      identification could lead to secondary prevention by controlling risk factors
      such as systolic hypertension. The amnestic subtype of mild cognitive impairment
      has a high risk of progression to Alzheimer's disease, and it could constitute a
      prodromal stage of this disorder. Other definitions and subtypes of mild
      cognitive impairment need to be studied as potential prodromes of Alzheimer's
      disease and other types of dementia.

PMID- 16631883
TI  - New genes in inflammatory bowel disease: lessons for complex diseases?
AB  - The chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis
      are common causes of gastrointestinal disease in northern Europe, affecting as
      many as one in 250 people. Although mortality is low, morbidity associated with
      these diseases is substantial. We review the recent advances in the genetics of
      inflammatory bowel disease, with particular emphasis on the data that have been
      generated since the discovery of the CARD15 (NOD2) gene in 2001.

PMID- 16631884
TI  - Role of parametric resonance in virological failure during HIV treatment
      interruption therapy.
AB  - We present a novel hypothesis that could explain virological failure to
      structured treatment interruptions (STI). We analysed a classic mathematical
      model of HIV within-host viral dynamics and found that non-linear parametric
      resonance occurs when STI are added to the model; resonance is observed as
      virological failure. We simulated clinical trial data and calculated patient
      specific resonant spectra. We gained two important insights. First, within an STI
      trial, patients who begin with similar viral loads can be expected to show very
      different virological responses as a result of resonance. Second, and more
      importantly, virological failure is not simply due to STI or patients'
      characteristics; instead it is the result of complex interaction between STI and
      the patient's viral dynamics. Hence, our analyses show that no universal regimen
      with periodic interruptions will be effective for all patients.

PMID- 16631885
TI  - The case of the forgotten address.

PMID- 16631886
TI  - Bio-reduction of arsenate using a hydrogen-based membrane biofilm reactor.
AB  - Arsenate (As(V)) is a carcinogen and a significant problem in groundwater in many
      parts of the world. Since As(III) is generally more mobile and more toxic than
      As(V), the reduction of As(V) to As(III) is not a conventional treatment goal.
      However, reducing As(V) to As(III) may still be a means for decontamination,
      because As(III) can be removed from solution by precipitation or complexation
      with sulfide or by adsorption to Fe(II)-based solids. A promising approach for
      reducing oxidized contaminants is the H2-based membrane biofilm reactor (MBfR).
      In the case of arsenate, the MBfR allows bio-reduction of As(V) to As(III) and
      sulfate to sulfide, thereby giving the potential for As removal, such as by
      precipitation of As2S3(s) or formation of Fe(II)-based solids. When As(V) was
      added to a denitrifying MBfR, As(V) was reduced immediately to As(III).
      Decreasing the influent sulfate loading increased As(V) reduction for a fixed H2
      pressure. A series of short-term experiments elaborated on how As(V) loading,
      nitrate and sulfate loadings, and H2 pressure controlled As(V) reduction. Lower
      nitrate loading and increased As(V) loading increased the extent of As(V)
      reduction, but increased H2 pressure did not increase As(V) reduction. As(V)
      reduction was sensitive to sulfate loading, with a maximum As(V)-removal
      percentage and flux with no addition of sulfate. As(III) could be precipitated
      with sulfide or adsorbed to Fe(II) solids, which was verified by scanning
      electron microscopy and energy dispersive X-ray analysis.

PMID- 16631887
TI  - Remediation of heavy metal polluted sediment in the solid bed: comparison of
      abiotic and microbial leaching.
AB  - Basic research on remediation of polluted sediment by leaching has, to date, been
      carried out exclusively with suspended material. For economic reasons, only solid
      bed leaching is applicable to large-scale processes. Abiotic and microbial solid
      bed leaching were comparatively studied in a percolator system using ripened and
      therefore permeable heavy metal polluted river sediment. In the case of abiotic
      leaching, sulfuric acid was supplied to the sediment by circulating water; the
      lower the pH of the percolating water, the higher the percolation flow, and the
      lower the solid-bed height was, the faster the heavy metals were solubilized.
      However, the pH and percolation flow are subjected to restrictions: strongly
      acidic conditions result in dissolution of mineral components, and the
      percolation flow must not exceed the bed permeability. And a high solid bed is an
      economic requirement. In the case of bioleaching, elemental sulfur added to the
      sediment was oxidized to sulfuric acid within the package which, in turn,
      solubilized the heavy metals. Here, the percolation flow and the solid-bed height
      did not affect the rate of metal solubilization. Solid-bed leaching on a larger
      scale will thus be much more efficient applying bioleaching with sulfur as the
      leaching agent than abiotic leaching with sulfuric acid.

PMID- 16631888
TI  - Relationship between VOC and NOx emissions and chemical production of
      tropospheric ozone in the Aburra Valley (Colombia).
AB  - Relationship between volatile organic compounds (VOC) and nitrogen oxides (NOx)
      emissions and the chemical production of tropospheric ozone is studied through
      mathematical simulation. The study is applied to the Aburra Valley, in the
      Colombian Andes, which is a practically unknown area from the point of view of
      ozone formation. The model used for this application is the European modelling of
      atmospheric constituents (EUMAC) zooming model (EZM) which consists of a
      mesoscale prognostic model (MEMO, mesoscale meteorological model) and a chemical
      reaction model (MUSE, multiscale for the atmospheric dispersion of reactive
      species), coupled to the chemical mechanism EMEP (European monitoring and
      evaluation program). The analysis is performed for a real episode that was
      characterized by high ozone production and that happened during the 23rd and 24th
      December, 1999 in Medellin (Colombia). From this real scenario, a sensitivity
      analysis has been carried out in order to assess the influence of VOC and NOx
      amounts on ozone production and to extract some conclusions for future ozone
      abatement policies in Andean regions. As far as ozone air quality is concerned,
      it is shown that in order to keep current levels the emphasis must be put to
      avoid increasing NOx emissions, or alternatively, to augment VOC emissions in
      order to have a high VOC/NOx ratio.

PMID- 16631889
TI  - Costs could derail Massachusetts health reforms.

PMID- 16631890
TI  - Germany's fatal stance on tobacco advertising.

PMID- 16631891
TI  - Who is responsible for trainee doctors' mistakes?

PMID- 16631892
TI  - Putting a value on medical research.

PMID- 16631893
TI  - Should eponyms be actively detached from diseases?

PMID- 16631894
TI  - Blushing: an embarrassing condition, but treatable.

PMID- 16631895
TI  - Vaccine for cervical cancer: reaching adolescents in sub-Saharan Africa.

PMID- 16631896
TI  - Joined-up public-health initiatives.

PMID- 16631897
TI  - Medical professionalism in Laos.

PMID- 16631899
TI  - Mikhail Balonov: understanding the legacy of Chernobyl.

PMID- 16631900
TI  - Controversies in cardiology.

PMID- 16631901
TI  - Controversies in cardiology.

PMID- 16631902
TI  - Controversies in cardiology.

PMID- 16631903
TI  - Controversies in cardiology.

PMID- 16631904
TI  - Controversies in cardiology.

PMID- 16631906
TI  - Maternal vitamin D status and childhood bone mass.

PMID- 16631907
TI  - Tobacco industry research on smoking and cigarette toxicity.

PMID- 16631910
TI  - Effect of a US National Institutes of Health programme of clinical trials on
      public health and costs.
AB  - BACKGROUND: Few attempts have been made to estimate the public return on
      investment in medical research. The total costs and benefits to society of a
      clinical trial, the final step in testing an intervention, can be estimated by
      evaluating the effect of trial results on medical care and health. METHODS: All
      phase III randomised trials funded by the US National Institute of Neurological
      Disorders and Stroke before Jan 1, 2000, were included. Pertinent publications on
      use, cost to society, and health effects for each studied intervention were
      identified by systematic review, supplemented with data from other public and
      proprietary sources. Regardless of whether a trial was positive or negative,
      information on use of tested therapies was integrated with published per-use data
      on costs and health effect (converted to 2004 US dollars) to generate 10-year
      projections for the US population. FINDINGS: 28 trials with a total cost of 335
      million dollars were included. Six trials (21%) resulted in measurable
      improvements in health, and four (14%) resulted in cost savings to society. At 10
      years, the programme of trials resulted in an estimated additional 470,000
      quality-adjusted life years at a total cost of 3.6 billion dollars (including
      costs of all trials and additional health-care and other expenditures). Valuing a
      quality-adjusted life year at per-head gross domestic product, the projected net
      benefit to society at 10-years was 15.2 billion dollars. 95% CIs did not include
      a net loss at 10 years. IMPLICATIONS: For this institute, the public return on
      investment in clinical trials has been substantial. Although results led to
      increases in health-care expenditures, health gains were large and valuable.

PMID- 16631911
TI  - Use in routine clinical practice of two commercial blood tests for diagnosis of
      infection with Mycobacterium tuberculosis: a prospective study.
AB  - BACKGROUND: Two commercial blood assays for the diagnosis of latent tuberculosis
      infection--T-SPOT.TB and QuantiFERON-TB Gold--have been separately compared with
      the tuberculin skin test. Our aim was to compare the efficacy of all three tests
      in the same population sample. METHODS: We did a prospective study in 393
      consecutively enrolled patients who were tested simultaneously with T-SPOT.TB and
      QuantiFERON-TB Gold because of suspected latent or active tuberculosis. 318
      patients also had results available for a tuberculin skin test. FINDINGS: Overall
      agreement with the skin test was similar (T-SPOT.TB kappa=0.508, QuantiFERON-TB
      Gold kappa=0.460), but fewer BCG-vaccinated individuals were identified as
      positive by the two blood assays than by the tuberculin skin test (p=0.003 for T
      SPOT.TB and p<0.0001 for QuantiFERON-TB Gold). Indeterminate results were
      significantly more frequent with QuantiFERON-TB Gold (11%, 43 of 383) than with T
      SPOT.TB (3%, 12 of 383; p<0.0001) and were associated with immunosuppressive
      treatments for both tests. Age younger than 5 years was significantly associated
      with indeterminate results with QuantiFERON-TB Gold (p=0.003), but not with T
      SPOT.TB. Overall, T-SPOT.TB produced significantly more positive results (38%,
      n=144, vs 26%, n=100, with QuantiFERON-TB Gold; p<0.0001), and close contacts of
      patients with active tuberculosis were more likely to be positive with T-SPOT.TB
      than with QuantiFERON-TB Gold (p=0.0010). INTERPRETATION: T-SPOT.TB and
      QuantiFERON-TB Gold have higher specificity than the tuberculin skin test. Rates
      of indeterminate and positive results, however, differ between the blood tests,
      suggesting that they might provide different results in routine clinical
      practice.

PMID- 16631912
TI  - Scaling up of highly active antiretroviral therapy in a rural district of Malawi:
      an effectiveness assessment.
AB  - BACKGROUND: The recording of outcomes from large-scale, simplified HAART (highly
      active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We
      aimed to assess the effectiveness of such a programme held by Medecins Sans
      Frontieres (MSF) in the Chiradzulu district, Malawi. METHODS: We scaled up and
      simplified HAART in this programme since August, 2002. We analysed survival
      indicators, CD4 count evolution, virological response, and adherence to
      treatment. We included adults who all started HAART 6 months or more before the
      analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed
      on a subsample of patients, and antiretroviral resistance mutations were analysed
      in plasma with viral loads greater than 1000 copies per mL. Analysis was by
      intention to treat. FINDINGS: Of the 1308 patients who were eligible, 827 (64%)
      were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%)
      received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose
      combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were
      at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208
      (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3
      months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%)
      were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass
      index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL
      were independent determinants of death in the first 6 months. At 12 months, the
      probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the
      median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey
      (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several
      indicators measuring adherence, self-reported poor adherence (<80%) in the past 4
      days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9
      15.6). INTERPRETATION: These data show that large numbers of people can rapidly
      benefit from antiretroviral therapy in rural resource-poor settings and strongly
      supports the implementation of such large-scale simplified programmes in Africa.

PMID- 16631913
TI  - Amblyopia.
AB  - Results from recent randomised clinical trials in amblyopia should change our
      approach to screening for and treatment of amblyopia. Based on the current
      evidence, if one screening session is used, screening at school entry could be
      the most reasonable time. Clinicians should preferably use age-appropriate LogMAR
      acuity tests, and treatment should only be considered for children who are
      clearly not in the typical range for their age. Any substantial refractive error
      should be corrected before further treatment is considered and the child should
      be followed in spectacles until no further improvement is recorded, which can
      take up to 6 months. Parents and carers should then be offered an informed choice
      between patching and atropine drops. Successful patching regimens can last as
      little as 1 h or 2 h a day, and successful atropine regimens as little as one
      drop twice a week. Intense and extended regimens might not be needed in initial
      therapy.

PMID- 16631914
TI  - Folic acid: a public-health challenge.
AB  - Despite worldwide public-health campaigns recommending periconceptional daily
      supplementation of synthetic folic acid to reduce the risk of neural tube
      defects, many women are not following these recommendations. At the same time, in
      most European countries no decline in defects has been recorded in recent years.
      Vulnerable groups are those with a low standard of education, young people, and
      women with unplanned pregnancies. Furthermore, in most countries without
      mandatory fortification, the general population is not consuming the recommended
      0.4 mg of food folate per day. Voluntary fortification improves the situation,
      but does not reach all parts of the population. In the USA, Canada, and Chile,
      mandatory fortification of flour substantially improved folate and homocysteine
      status, and neural tube defects rates fell by between 31% and 78%. Nevertheless,
      many countries do not choose mandatory folic acid fortification, in part because
      expected additional health benefits are not yet scientifically proven in clinical
      trials, in part because of feared health risks, and because of the issue of
      freedom of choice. Thus, additional creative public-health approaches need to be
      developed to prevent neural tube defects and improve the folate status of the
      general population.

PMID- 16631915
TI  - Wegener's granulomatosis.

PMID- 16631916
TI  - Social consequences of antiretroviral therapy: preparing for the unexpected
      futures of HIV-positive children.

PMID- 16631917
TI  - Ocular ischaemic syndrome: a medical emergency.

PMID- 16631918
TI  - Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta
      subunit, a reliable marker of placental site trophoblastic tumors.
AB  - OBJECTIVES: Placental site trophoblastic tumor (PSTT) commonly presents with low
      and variable concentration of hCG immunoreactivity in serum which can be
      difficult to differentiate from early stage choriocarcinoma/gestational
      trophoblastic neoplasm (GTN) or quiescent gestational trophoblastic disease
      (quiescent GTD). Nontrophoblastic malignancies such as germ cell tumors or other
      tumors secreting low hCG must also be considered in the differential diagnosis.
      Because treatments for these conditions are different, a means of differentiating
      PSTT from other diagnoses is important. We investigate the usefulness of hCG-free
      beta-subunit to make this discrimination. METHODS: Data collected on cases
      referred to the USA hCG Reference Service for consultation served as a basis for
      this retrospective analysis. There were 13 cases with histology proven PSTT and
      12 with nontrophoblastic malignancy. hCG-free beta-subunit was measured by
      immunoassay and reported as a proportion of total hCG (hCG-free beta-subunit(%)).
      hCG-free beta-subunit(%) results were determined for all histologically proven
      cases of PSTT and for the nontrophoblastic malignancies. Comparisons of hCG-free
      beta-subunit(%) were made and compared with those of the 82 choriocarcinoma/GTN
      cases and 69 quiescent GTD cases. The accuracy of hCG-free beta-subunit(%) to
      discriminate these malignancies was analyzed by investigating the areas under
      receiver-operating characteristics curve +/- standard error. RESULTS: hCG-free
      beta-subunit(%) was the predominant hCG form in cases of PSTT (mean +/- standard
      deviation, 60 +/- 19%) and nontrophoblastic malignancies (91 +/- 11%), thus
      discriminating these diagnoses from choriocarcinoma/GTN (9.3 +/- 9.2%) and from
      quiescent GTD (5.4 +/- 7.8%). The cutoff of >35% free beta-subunit is proposed.
      At this cutoff, 100% detection at 0% false-positive is achieved. The accuracy of
      hCG-free beta-subunit(%) for this discrimination is 100 +/- 0%. At a proposed
      cutoff of >80%, the free beta-subunit test will also distinguish PSTT from
      nontrophoblastic malignancy, with 77% detection at 23% false-positive or an
      accuracy of 92 +/- 3.2%. CONCLUSION: Measurement of the proportion hCG-free beta
      subunit(%) was found to be useful in the diagnosis of PSTT using proposed cutoff
      values of >35% and >80%. While this finding needs to be confirmed by larger
      studies, it would be reasonable to measure hCG-free beta-subunit(%) whenever the
      diagnosis of PSTT is considered.

PMID- 16631919
TI  - Splenectomy as part of cytoreductive surgery in ovarian cancer.
AB  - OBJECTIVE: Epithelial ovarian carcinoma with extensive upper abdominal disease
      may require splenectomy for optimal tumor cytoreduction. We describe patients who
      required splenectomy during tumor reduction procedures for primary or recurrent
      epithelial ovarian carcinoma. METHODS: Data were abstracted from records of 112
      patients who underwent splenectomy as part of primary or secondary cytoreductive
      surgery. RESULTS: Of 112 patients, 66 had primary and 46 had secondary
      cytoreduction. Some patients also required bowel resection (50%), formal
      lymphadenectomy (31%), or urinary tract resection (5%). The most common
      indications for splenectomy were direct metastatic involvement (46%),
      facilitation of an en bloc resection of perisplenic disease (41%), and
      intraoperative trauma (13%). Histologically, 65% had hilar involvement; 52%,
      capsular involvement; and 16%, parenchymal metastases. Short-term complications
      included wound infections (7), pneumonias (5), thromboembolic events (9), and
      sepsis (5). Sepsis was associated with an anastomotic bowel leak in 1 patient,
      with fungal infections in 2 patients (1 pneumonia and 1 pelvic abscess), and with
      no identifiable infectious source in 2. Two patients required reoperation for
      bleeding: 1 for diffuse intraabdominal bleeding, including the splenic bed, and 1
      for pelvic sidewall bleeding. The perioperative mortality rate at splenectomy was
      5%: 3 from sepsis (1 anastomotic leak, 2 pneumonias), 2 from pulmonary embolism,
      and 1 for which the precise cause of death was not ascertainable. The primary
      cytoreduction group had a median survival of 1.8 years, with an estimated 2-year
      survival rate of 46%. The median survival in the secondary debulking group was
      1.7 years, with an estimated 2-year survival of 42%. CONCLUSIONS: In patients
      with clinically significant upper abdominal disease, splenectomy as part of
      primary or secondary cytoreductive surgery is associated with modest morbidity
      and mortality. The risk-benefit ratio of aggressive surgical cytoreduction must
      be considered.

PMID- 16631920
TI  - Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG.
AB  - OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG
      produced by cytotrophoblast cells at implantation of pregnancy and in
      choriocarcinoma. We investigated the biological function of hCG-H in invasion in
      vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and
      cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of
      total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and
      100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the
      action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on
      3 different lines of choriocarcinoma cells cultured on Matrigel basement membrane
      inserts (culture models for assessing tumor invasion). The addition of hCG-H to
      medium significantly promoted invasion of membranes with both pregnancy and
      cancer cell line sources, while regular hCG had no significant effect. JEG-3
      human choriocarcinoma cells were transplanted subcutaneously into athymic nude
      mice. Tumors rapidly formed. B152, mouse monoclonal antibody against hCG-H, and
      non-specific mouse IgG (control) were administered twice weekly once tumors were
      clearly visible. While a correlation between time and growth was observed with
      the control group (r(2)=0.97), no correlation was observed with the B152-treated
      mice (r(2)=0.15). B152 blocked tumor growth (t test, IgG vs. B152, P=0.003). In a
      second experiment, antibody B152 or IgG was administered to mice at the time of
      choriocarcinoma transplantation. B152 significantly inhibited tumorigenesis (t
      test P=0.0071). CONCLUSIONS: hCG-H is a critical promoter in human
      cytotrophoblast and human choriocarcinoma cell invasion in vivo and in vitro,
      promoting tumor growth and invasion through an autocrine mechanism. hCG-H is a
      signal for choriocarcinoma cell invasion, making it a biological tumor marker.
      Antibodies against hCG-H block tumor formation and growth. Human or humanized
      antibodies against hCG-H may be useful in treating and managing choriocarcinoma
      and other gestational trophoblastic malignancies.

PMID- 16631921
TI  - Differential effects of delta9-THC on learning in adolescent and adult rats.
AB  - Marijuana use remains strikingly high among young users in the U.S., and yet few
      studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in
      adolescents compared to adults. This study measured the effects of THC on male
      adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent
      (PD=30-32) and adult (PD=65-70) rats were treated acutely with 5.0 mg/kg THC or
      vehicle while trained on the spatial version of the water maze on five
      consecutive days. In Experiment 2, adolescent and adult rats were treated acutely
      with 2.5 or 10.0 mg/kg THC or vehicle while trained on either the spatial and non
      spatial versions of the water maze. In Experiment 3, adolescent and adult rats
      were treated with 5.0 mg/kg THC or vehicle daily for 21 days, and were trained on
      the spatial and then the non-spatial versions of the water maze task four weeks
      later in the absence of THC. THC impaired both spatial and nonspatial learning
      more in adolescents than in adults at all doses tested. However, there were no
      long-lasting significant effects on either spatial or non-spatial learning in
      rats that had been previously exposed to THC for 21 days. This developmental
      sensitivity is analogous to the effects of ethanol, another commonly used
      recreational drug.

PMID- 16631922
TI  - Changes in the translucency of porcelain and repairing resin composite by the
      illumination.
AB  - OBJECTIVES: The objectives were to evaluate the difference in the translucency
      parameter (TP) by the illuminants, to determine the correlation between the
      contrast ratio (CR) and three TP values relative to the illuminants, and to
      measure the correlation between the differences in TP (DeltaTP) and color
      (DeltaE(ab)*) by the illuminants based on dental porcelain and porcelain
      repairing resin composites. METHODS: Color and spectral reflectance of three
      shades of one dental porcelain and three porcelain repairing resin composites
      were measured before and after thermocycling for 3000 cycles relative to the CIE
      standard illuminants D65, A and F2 over a white and a black backgrounds. Specimen
      was 1.8mm in thickness after polishing. CR was calculated, and the differences in
      TP and color caused by the change of illuminants were compared. Three-way
      analysis of variance by the material (porcelain or resin composite), shade and
      illuminant was used to compare differences (alpha=0.05). RESULTS: The TP value
      was influenced by the illuminant (p<0.05), and the TP values relative to the
      illuminants A and F2 were higher than those relative to D65. The correlation
      coefficients between the CR and three TP relative to the three illuminants were
      around -0.95. Color difference was positively correlated with the difference in
      translucency in resin composites (r=0.65 between A and D65 and 0.47 between F2
      and D65), but was negatively correlated in porcelain (r=-0.37 between A and D65
      and -0.69 between F2 and D65). SIGNIFICANCE: Difference in translucency by
      illumination should be considered when matching shade of porcelain and repairing
      resin composite.

PMID- 16631923
TI  - Effect of mechanical cycling on the flexural strength of densely sintered
      ceramics.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of mechanical
      cycling on the biaxial flexural strength of two densely sintered ceramic
      materials. METHODS: Disc shaped zirconia (In-Ceram Zirconia) and high alumina
      (Procera AllCeram) ceramic specimens (diameter: 15 mm and thickness: 1.2 mm) were
      fabricated according to the manufacturers' instructions. The specimens from each
      ceramic material (N=40, n=10/per group) were tested for flexural strength either
      with or without being subjected to mechanical cycling (20,000 cycles under 50 N
      load, immersion in distilled water at 37 degrees C) in a universal testing
      machine (1 mm/min). Data were statistically analyzed using two-way ANOVA and
      Tukey's test (alpha=0.05). RESULTS: High alumina ceramic specimens revealed
      significantly higher flexural strength values without and with mechanical cycling
      (647+/-48 and 630+/-43 MPa, respectively) than those of zirconia ceramic (497+/
      35 and 458+/-53 MPa, respectively) (p<0.05). Mechanical cycling for 20,000 times
      under 50 N decreased the flexural strength values for both high alumina and
      zirconia ceramic but it was not statistically significant (p>0.05). SIGNIFICANCE:
      High alumina ceramic revealed significantly higher mean flexural strength values
      than that of zirconia ceramic tested in this study either with or without
      mechanical cycling conditions.

PMID- 16631924
TI  - The effect of enamel porcelain thickness on color and the ability of a shade
      guide to prescribe chroma.
AB  - OBJECTIVE: To test the null hypothesis that there is no color change when enamel
      porcelain thickness is changed and to evaluate the ability of a shade guide to
      prescribe chroma. METHODS: Three shades (3M1, 3M2 and 3M3) were selected from a
      Vitapan 3D master shade guide. Five disk specimens were prepared for each shade,
      consisting of three layers (opacious dentin, dentin and enamel) at thicknesses of
      0.6, 0.8 and 0.6mm, respectively. The color of each disk was measured using a
      spectrophotometer. Enamel porcelain was reduced in thickness to 0.3mm and
      porcelain disks were remeasured. RESULTS: Reducing the enamel thickness of
      porcelain disk specimens significantly increased L) (p<0.05), b*, metric chroma
      and hue angle (p<0.001). For the three shades studied (3M1, 3M2 and 3M3) L*
      values were not significantly different (p>0.05) and chroma increased for 3M1
      with the lowest chroma to 3M3 with the highest chroma, which is in line with the
      shade guide specifications. Although statistically significant (p<0.001) changes
      in hue angle between the three shades were small (less than 3 degrees overall).
      The difference in chroma between the three shades 3M1, 3M2 and 3M3 was greatest
      for the thin enamel layer than the thick enamel layer. SIGNIFICANCE: A change in
      enamel thickness from 0.6 to 0.3mm resulted in a three-unit change in L* and
      metric chroma and a 4 degrees change in hue angle. A change in enamel porcelain
      thickness will have a greater effect on higher chromatic shades than those with
      lower chroma. The ability of the shade guide to prescribe chroma was demonstrated
      but this could be offset by an anomalous enamel thickness.

PMID- 16631925
TI  - Coping and suicidality among homeless youth.
AB  - This study examined the impact of coping strategies employed by homeless youth
      upon suicidal ideation, suicide attempts on the streets, and feeling
      trapped/helpless. Coping strategies examined in the analysis included problem
      focused and avoidant coping, along with several coping strategies identified in
      previous exploratory qualitative studies. Greater risk was associated with
      avoidant coping, social withdrawal, use of drugs and alcohol as coping, with
      "belief in a better future" linked to lowered risk levels. Gender interactions
      emerged with respect to avoidant coping and social withdrawal, both of which
      served as greater contributors to risk levels among females. Several approaches
      to coping including problem-focused strategies and strategies identified by
      youths in previous qualitative works emerged as not serving to ameliorate
      suicidality.

PMID- 16631926
TI  - Analysis of secreted protease inhibitors after water stress in potato tubers.
AB  - Potato tubers (Solanum tuberosum) secrete two kinds of proteinase inhibitors
      after a water stress. The polypeptides have differing inhibitory activities but
      are Kunitz-type inhibitors based on amino-terminal sequences homologies. A
      proteolysis maturation type of a cell protease inhibitor was observed. They can
      constitute high MW complex, sometimes with another type of protein. The function
      of these protease inhibitors is discussed in relation to plant defence.

PMID- 16631927
TI  - Tissue inhibitors of metalloproteinases-1 (TIMP-1) and -2(TIMP-2) are major serum
      factors that stimulate the TIMP-1 gene in human gingival fibroblasts.
AB  - We demonstrate in this study that both TIMP-1 and TIMP-2 are major serum factors
      that stimulate the induction of TIMP-1 mRNA in quiescent human gingival
      fibroblasts (Gin-1 cells) at mid-G1 (6-9 h after serum stimulation) of the cell
      cycle, but not that of TIMP-2. When we chased the secretion of both TIMP proteins
      into culture medium containing 10% FCS freed of both TIMPs, TIMP-2 secretion rose
      to the level in 10% FCS after 24 h, but TIMP-1 secretion remained at a fairly low
      level even after 3 days, thus reflecting a contrastive difference in the
      induction of both TIMP mRNAs. The stimulating activity of TIMP-1 on the
      expression of the TIMP-1 gene switched over to inhibitory activity, when the TIMP
      1 concentration in the culture medium exceeded about 30 ng/ml. The depletion of
      TIMP-1 and TIMP-2 from FCS affected remarkably the induction of c-jun and c-fos
      mRNAs, but not that of c-ets-1 mRNA. TIMP-1 and TIMP-2-dependent expression of AP
      1 protein was further demonstrated by using nuclear extracts of Gin-1 cells in an
      electrophoretic mobility shift assay.

PMID- 16631929
TI  - Cognitive functions related to interpersonal problem-solving skills in
      schizophrenic patients compared with healthy subjects.
AB  - Subjects with schizophrenia have cognitive alterations. The functional
      consequences of these deficits need to be fully determined, in order to implement
      more effective rehabilitation programs for patients with schizophrenia. This
      research explores the relationships between cognitive functioning and social
      problem-solving skills in a group of 20 chronic schizophrenic patients compared
      with those found in a group of 20 healthy subjects. The following cognitive
      domains were evaluated: verbal memory (Rey Auditory-Verbal Test; RAVLT), visuo
      spatial organization and visuo-spatial memory (Rey-Osterrieth complex figure
      test; RF), executive functioning (semantic verbal fluency test; VF, design
      fluency task; DF and Wisconsin Card Sorting Test; WCST), attention (d 2
      cancellation test) and general intellectual ability (Standard Progressive
      Matrices of Raven; SPM). Social problem-solving skills were assessed with a video
      based test; the Assessment of Interpersonal Problem-Solving Skills (AIPSS). As a
      group, patients performed significantly worse than control subjects on every
      cognitive variable and on AIPSS receiving, processing and sending constructs.
      Among schizophrenic patients, correlations between AIPSS constructs and
      neuropsychological tests were observed for VF, DF, d2 and SPM whilst these
      associations were not replicated in healthy subjects. However, in the whole
      sample, after adjusting for age, gender and education, SPM displayed significant
      associations with all three AIPSS constructs. Moreover, after taking SPM into
      account, neither diagnostic groups (patients versus control) nor cognitive
      variables, except d2, provided an additional contribution to AIPSS performance.
      Cognitive impaired performances, mainly frontal, have a deleterious effect on
      social problem-solving skills in the schizophrenic group. It is suggested that
      alterations in social problem-solving skills may reflect social anxiety and/or "
      theory of mind " impairment. These factors may explain the lack of association
      among healthy subjects. The results support the inclusion of cognitive
      remediation programs designed to enhance social skills for patients where a
      cognitive deficit is clearly ascertained.

PMID- 16631928
TI  - Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG
      immune responses in mice and in cynomolgus monkeys.
AB  - The complement system and B cell complement receptor 2 (CR2), specific for C
      component C3dg, play important roles in both the innate and adaptive immune
      response. We used hapten and protein conjugates of anti-CR2 mAbs as models for
      C3dg-opsonized antigens and immune complexes to examine the handling of and
      immune response to these reagents in mice and in non-human primates (NHP). Mice
      immunized and boosted i.v. with only 100 ng of Alexa 488 rat anti-mouse CR1/2 mAb
      7G6 had strong IgG immune responses to the Alexa 488 hapten and to rat IgG,
      compared to very weak immune responses in mice treated with a comparable isotype
      control; larger doses of Alexa 488 mAb 7G6 did not increase the immune response.
      A vaccine constructed by cross-linking anthrax protective antigen to mAb 7G6
      proved to be effective at low doses in generating sufficiently high titer serum
      IgG antibodies to neutralize anthrax lethal toxin in vitro and to protect mice
      from i.v. challenge with anthrax lethal toxin. When biotinylated HB135, a mouse
      mAb specific for human CR2, was injected i.v. into NHP, the probe manifested the
      same initial marginal zone B cell binding and subsequent localization to
      follicular dendritic cells as we have previously reported for comparable
      experiments in mice. Moreover, i.v. immunization of NHP with 1 microg/kg of Alexa
      488 mAb HB135 promoted an IgG immune response to the Alexa 488 hapten and to
      mouse IgG. Taken together, these results demonstrate the efficacy of using anti
      CR2 mAbs as antigen carriers for i.v. immunization with small amounts of antigens
      without adjuvant.

PMID- 16631930
TI  - Trait modulation of alcohol-induced laboratory aggression.
AB  - Modest alcohol and aggressive trait effects on laboratory-induced aggression
      among men have been reported with some consistency in the literature.
      Relationships between aggressive personality traits and laboratory-induced
      aggression appear to become less consistent under the influence of alcohol.
      Several research teams have found suggestions that the effects of alcohol on
      laboratory aggression may be reduced or even reversed among individuals with
      aggressive personality traits. This study examined the effects of alcohol on the
      aggressive responding on the Point Subtraction Aggression Paradigm (PSAP) of
      eight undergraduate men who generated evidence on the Million Clinical Multiaxial
      Inventory-II (MCMI-II) of sadistic-aggressive personality disorder features. This
      sample was compared with a group of 18 undergraduate male peers without MCMI-II
      elevations described in a previous study. Neither alcohol ingestion (0.8 ml/kg)
      nor aggressive personality traits predicted laboratory behavior in isolation, but
      alcohol was found to selectively attenuate (d = 0.75) PSAP responding for the
      sadistic-aggressive as opposed to the control subjects (i.e., a significant
      aggressive trait by alcohol interaction). The possible value of this
      counterintuitive response tendency in identifying men at elevated risk for
      alcohol-related aggression was discussed. Large, immediate reductions in
      laboratory-based aggressive responding while under the influence of alcohol might
      provide a paradoxical high risk indicator that has not been previously
      identified.

PMID- 16631931
TI  - Influence of antipsychotic medication on pain perception in schizophrenia.
AB  - A number of clinical observations indicate that pain processing might be
      disturbed in psychotic disorders such as schizophrenia. Only a few studies have
      investigated pain perception in schizophrenia. The main objective of this study
      was the investigation of thresholds of warmth perception (WP), thermal pain onset
      (TPO) and thermal pain tolerance (TPT) in acute schizophrenic patients and the
      influence of antipsychotic medication on the patients' responses. We investigated
      23 schizophrenic subjects who had been not received antipsychotic treatment for 8
      weeks, and we then reassessed them 3 days later after the introduction of
      neuroleptics. Acute symptoms of schizophrenia were measured using the Scales for
      the Assessment of Positive and Negative Symptoms. Thresholds were determined by a
      contact thermode on both volar wrists. Schizophrenic patients showed
      significantly increased thresholds of WP and TPO relative to healthy controls.
      Antipsychotics did not alter pain thresholds. We found no correlation between
      pain perception and psychometric scales. Our findings demonstrate altered warmth
      and heat pain perception in acute schizophrenia. We believe that our findings can
      be attributed to information-processing abnormalities of the disorder and that
      they are not specific to pain processing, per se, since both WP and TPO were
      significantly different. Future studies should evaluate attentional deficits in
      schizophrenia in relation to pain perception.

PMID- 16631932
TI  - Characterization of bioactive recombinant woodchuck interleukin-2 amplified by
      RLM-RACE and produced in eukaryotic expression system.
AB  - Woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV)
      represent a highly valuable laboratory model of hepatitis B virus (HBV)
      infection, in which molecular, immunological and pathological events occurring in
      infected humans are adequately reflected. To advance studies on T cell immune
      responses and propagation of hepadnavirus in T lymphocytes in this animal model,
      we determined the complete sequence of woodchuck interleukin-2 (wIL-2) cDNA by
      utilizing RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE)
      reaction. The wIL-2 sequence revealed a single open reading frame encoding for
      the predicted precursor protein comprised of a signal peptide and a 134 amino
      acid-long mature protein. The mature wIL-2 protein produced in the Escherichia
      coli expression system, designated as ec-rwIL-2, was found to be immunogenic but
      not biologically active. In contrast, precursor wIL-2 protein cloned into
      baculovirus transfer vector and expressed in Sf9 cells, designated as bac-rwIL-2,
      demonstrated functional competence. Further, bac-rwIL-2 was able to stimulate
      proliferation and to induce multiple daughter cell generations in woodchuck T
      cells, as well as facilitated the survival of standard IL-2-dependent mouse CTLL
      2 cells in culture. Western blot analysis of bac-rwIL-2 using antibodies
      generated against ec-rwIL-2 revealed a single protein band of 15.5kDa. The
      availability of biologically active recombinant wIL-2 should facilitate ex vivo
      studies on functional competence of woodchuck T lymphocytes derived from
      different stages of hepadnaviral hepatitis and assist in recognizing their
      contribution to the pathogenesis of liver injury in the woodchuck model of
      hepatitis B.

PMID- 16631933
TI  - T-cell apoptosis in human glioblastoma multiforme: implications for
      immunotherapy.
AB  - We used immunohistochemistry and flow cytometry to assess apoptosis in human
      glioblastoma multiforme (GBM). Our immunohistochemical study revealed apoptosis
      of glioma cells expressing glial fibrillary acidic protein and of CD3(+) T cells
      infiltrating GBM. To quantify and phenotype the apoptotic T cells, we performed
      flow cytometry on lymphocytes separated from GBM. The cells were stained with
      annexin-V-FLUOS/propidium iodide to identify apoptosis. We found that high
      proportions of both the CD4(+) and CD8(+) T cells were apoptotic. In particular,
      we found that T cells expressing Fas ligand (Fas-L, CD95L) were eight times more
      vulnerable to apoptosis than those not expressing Fas-L, which suggests that the
      T-cell apoptosis is induced by overactivation of the T-cell receptor, possibly in
      the absence of appropriate costimulation. Our results have implications for the
      design of immunotherapies for GBM.

PMID- 16631934
TI  - BDNF: a missing link between sympathetic dysfunction and inflammatory disease?
AB  - Nerve growth factor (NGF) plays a role in sympathetic neuron integrity and
      survival. Brain-derived neurotrophic factor (BDNF) also has trophic effects on
      sympathetic neurons. We report here the serendipitous finding that co-treatment
      of hippocampus with BDNF and the NGF antagonist TrkA-Fc leads to perivascular
      inflammation and marked vasoconstriction. This effect is not observed with either
      reagent alone or in combination with other control proteins. Because NGF supports
      sympathetic neuron health, we tested the hypothesis that BDNF combined with
      sympathetic compromise caused this effect. Superior cervical ganglia were removed
      bilaterally with concurrent BDNF infusion into hippocampus. Perivascular
      inflammation was observed at 3 days, but not 12 days post treatment, when
      sympathetic terminals had receded, suggesting that the presence of these
      terminals was necessary for inflammation. Since sympathetic dysfunction may lead
      to compensatory overactivity of norepinephrine (NE) signaling, we co-infused BDNF
      with NE in the hippocampus and observed perivascular inflammation. In humans,
      sympathetic overactivity has been reported in a variety of vascular diseases.
      Some of these diseases, e.g. primary Raynaud's, are not accompanied by serious
      inflammatory disease whereas others, such as scleroderma and systemic lupus, are.
      We speculate that BDNF may contribute to the transformation of sympathetic
      dysfunction to inflammatory disease.

PMID- 16631935
TI  - An ecotoxicoproteomic approach (SELDI-TOF mass spectrometry) to biomarker
      discovery in crab exposed to pollutants under laboratory conditions.
AB  - Ciphergen ProteinChip Technology is a proteomic tool, used for the discovery of
      new and sensitive biomarkers. This approach was used to evaluate the protein
      profile of crabs exposed to various pollutants. Two different exposure
      experiments were performed: spider crabs (Hyas araneus) were exposed for 3 weeks
      to diallyl phatalate (DAP), bisphenol A (BisA) and polybrominated diphenyl ether
      (PBDE-47), while shore crabs (Carcinus maeanas) were exposed to crude oil, crude
      oil spiked with alkylphenols (APs) and 4-nonylphenol (NP). Gender and species
      related protein pattern alterations were observed and compared to controls.
      Results showed different responses to pollutants by the two species. Major
      disruption in protein peak expression was observed in samples exposed to mixtures
      of pollutants, i.e. oil spiked with APs. Compared to shore crab, spider crab
      species showed a lower degree of response in terms of number of altered protein
      peaks following exposure. In general, female individuals of both species showed a
      larger number of significantly altered proteins compared to males. Data analysis
      by non-metric multi-dimensional scaling (MDS) was performed. Bi-dimesional-MDS
      plots revealed a good separation of groups for both spider and shore crabs. In
      some cases, a good discrimination can also be observed between the two genders
      within each treatment. Results highlight the potential of crabs as sentinel
      organisms for the aquatic environment. The results indicate that SELDI-ToF
      technology is a powerful tool to discover protein expression signatures for
      different pollutants and sex dependent responses.

PMID- 16631936
TI  - Background for the BEEP Stavanger workshops: Biological effects on marine
      organisms in two common, large, laboratory experiments and in a field study.
      Comparison of the value (sensitivity, specificity, etc.) of core and new
      biomarkers.

PMID- 16631937
TI  - Autosomal recessive plasma cell panniculitis with morphea-like clinical
      manifestation.
AB  - Two siblings had hyperpigmented indurations over the inner aspects of both thighs
      extending to the lower abdomen. Skin biopsy showed plasma cell panniculitis
      favoring a diagnosis of morphea profundus. Family history of consanguinity was
      present, but both parents were unaffected. To our knowledge this is the first
      report of autosomal recessive plasma cell panniculitis with the clinical
      manifestations of morphea.

PMID- 16631938
TI  - Extranodal nasal-type natural killer T-cell lymphoma in an adolescent from
      Bangladesh.
AB  - Natural killer (NK)-cell neoplasms are relatively uncommon tumors. Classification
      schemes prior to that of the World Health Organization (2001) did not account
      clearly for these neoplasms. Advances in immunohematology over the past 10 years
      have aided in the recognition and categorization of NK-cell tumors. One type of
      tumor that belongs to this class is extranodal, nasal-type NK/T-cell lymphoma.
      These lymphoma cells express a cytotoxic T-cell or NK-cell phenotype, including
      CD56 and TIA-1. Nasal-type NK/T-cell lymphomas arise from extranasal sites such
      as the skin and are often associated with Epstein-Barr virus infection. Asian
      adults are affected most commonly. Very few pediatric cases are reported in the
      literature, of which only 5 presented with cutaneous involvement. We report a
      case of an adolescent Bangladeshi boy with extranodal, nasal-type NK/T-cell
      lymphoma who had cutaneous nodules on the extremities.

PMID- 16631939
TI  - Minimal residual disease in hypopigmented mycosis fungoides.
AB  - We describe the case of a 13-year-old boy with stage I hypopigmented mycosis
      fungoides in whom minimal residual disease was detected with T-cell receptor
      gamma-polymerase chain reaction after the disease was in complete clinical
      remission. We further cloned and sequenced the T-cell receptor gamma-polymerase
      chain reaction product of the lesion in remission and found that the original T
      cell clone still existed in decreased amounts. The patient was followed up for 3
      1/2 years without any new lesions developing. The clinical significance of this
      residual malignant T-cell clone in mycosis fungoides remains to be elucidated.

PMID- 16631940
TI  - Conjugal transformed mycosis fungoides: the unknown role of viral infection and
      environmental exposures in the development of cutaneous T-cell lymphoma.
AB  - The etiology of mycosis fungoides (MF) is uncertain, although infectious agents
      and other environmental exposures have been implicated. We describe what appears
      to be the first case in which both a husband and his wife were diagnosed with
      large-cell transformation of MF. After 10 years of having stage I MF, the wife
      developed tumors that showed sheets of large transformed cells with dysplastic
      nuclei on skin biopsies, leading to a diagnosis of transformed MF. Her husband
      was diagnosed 14 months later with transformed MF following a biopsy of his right
      arm and leg after a 15-year history of presumed psoriasis. The fact that this
      rare occurrence happened in a couple who had been married for more than 25 years
      points to a common environmental exposure. Future studies should aim to clarify
      the potential role of infectious agents, such as human T-lymphotropic virus I and
      II, cytomegalovirus, Epstein-Barr virus, and other environmental exposures, in
      the development of MF.

PMID- 16631941
TI  - Dermatitis herpetiformis and partial IgA deficiency.
AB  - Although the specific IgA autoantibody responsible for the pathogenesis of
      dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered
      essential in the pathogenesis of DH. To date, no cases of IgA deficiency have
      been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients
      with celiac disease, a rate 10 to 15 times higher than the normal population. We
      report 2 patients with DH who also have partial IgA deficiency. We evaluated the
      sera of these patients for the presence of IgA autoantibodies to endomysium,
      tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients
      were found to have IgA endomysial and tissue transglutaminase antibodies, and
      serologic markers for DH. Corresponding IgG autoantibodies were not useful
      serologic markers of DH in the setting of IgA deficiency, as they often are in
      celiac disease. We then screened 98 DH sera for total IgA levels and identified 1
      additional case with IgA deficiency. In conclusion, DH may develop in patients
      with partial IgA deficiency, indicating that pathogenically directed IgA
      antibodies are likely sufficient for cutaneous IgA deposition in this disease.

PMID- 16631942
TI  - Recurrent syncope and anaphylaxis as presentation of systemic mastocytosis in a
      pediatric patient: case report and literature review.
AB  - Mastocytosis refers to a rare collection of disorders, both cutaneous and
      systemic, that are characterized by increased numbers of mast cells. Depending on
      the extent of the disease, these disorders may present with symptoms resulting
      from mast cell degranulation including flushing, diarrhea, vomiting, cramping,
      syncope, or anaphylaxis. In pediatric patients, cutaneous involvement is most
      prevalent in the form of urticaria pigmentosa, which is typically asymptomatic or
      minimally so with resolution by adolescence. In this case report and review of
      literature, we review a case of a 3-year-old child with uritcaria pigmentosa
      displaying recurrent syncope and anaphylaxis as the first presentation of
      systemic mastocytosis. We found data to be limited on this topic, and concluded
      that pediatric patients with prior diagnoses of cutaneous mastocytosis could
      benefit from either more aggressive screening for systemic disease or
      prophylactic treatment with antihistamines and rescue subcutaneous epinephrine.

PMID- 16631943
TI  - Multifocal lymphangioendotheliomatosis with thrombocytopenia.
AB  - Multifocal lymphangioendotheliomatosis with thrombocytopenia is an extremely rare
      disease. This condition manifests as diffuse congenital vascular lesions in the
      skin and gastrointestinal tract leading to severe gastrointestinal bleeding and
      thrombocytopenia. Histopathologic and immunohistochemical studies of vascular
      lesions demonstrate a lymphatic endothelial cell origin. Treatment often is not
      satisfactory. We herein describe a 4-week-old infant with this uncommon
      clinicopathologic entity.

PMID- 16631944
TI  - Keratoacanthoma centrifugum marginatum: response to topical 5-fluorouracil.
AB  - Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of
      keratoacanthoma, characterized by progressive peripheral growth with concomitant
      healing of the central area of the tumor. We present a patient with KCM who was
      treated with topical 5% 5-fluorouracil. This is the third reported case of KCM
      treated with this agent.

PMID- 16631945
TI  - Primary cutaneous paraganglioma of the scalp.
AB  - Paragangliomas are neuroendocrine tumors that arise in relation to the
      sympathetic or parasympathetic ganglia of the autonomic nervous system. Rarely,
      they are reported in unusual locations such as the urinary bladder, prostate, and
      uterus. Herein, we report a case of primary cutaneous paraganglioma of the scalp
      in a child. The tumor was studied histologically, immunohistochemically, and
      ultrastructurally. This case might represent an aberrant migration of neural
      crest cells in their descent toward the branchial arches. In addition, it
      highlights the complex interaction of the neural crest and branchial
      arches/clefts during embryogenesis.

PMID- 16631947
TI  - Treatment of primary cutaneous CD30+ anaplastic large cell lymphoma with
      intralesional methotrexate.

PMID- 16631946
TI  - Ecthyma gangrenosum and septic shock syndrome secondary to Chromobacterium
      violaceum.
AB  - Chromobacterium violaceum is a gram-negative bacterium of soil and water in
      tropical and subtropical environments. Typically, it is considered a bacterium of
      low virulence although, uncommonly, it causes human infection, particularly in
      persons with defects in host defenses. Infection generally follows exposure of
      broken skin to contaminated water and soil, and is often characterized by
      pustules, lymphadenitis, fever, and vomiting, as well as rapid dissemination and
      a high mortality rate. Unfortunately, because C violaceum is ubiquitous, it is
      often dismissed as a contaminant when cultured. Because rapid diagnosis (by
      taking appropriate specimens) and treatment are vital to a good prognosis, it is
      imperative that physicians be aware of this organism. In addition, patients with
      chromobacterial infections should have an immunologic workup because infections
      in immunocompetent individuals are rare. Here we report an aggressive yet
      nonfatal case of C violaceum septicemia in an adolescent male, diagnosed through
      a punch biopsy of a skin lesion, and resulting in a new diagnosis of chronic
      granulomatous disease.

PMID- 16631948
TI  - Contact dermatitis caused by baby wipes.

PMID- 16631949
TI  - Relapse of Wells' syndrome in a child after tetanus-diphtheria immunization.

PMID- 16631950
TI  - Treatment of verrucous carcinoma with topical imiquimod.

PMID- 16631951
TI  - Adherence with topical treatment is poor compared with adherence with oral
      agents: implications for effective clinical use of topical agents.

PMID- 16631952
TI  - Atypical generalized granuloma annulare associated with two visceral cancers.

PMID- 16631953
TI  - Autologous in vitro reconstituted epidermis in the treatment of a large nevus
      depigmentosus.

PMID- 16631954
TI  - Papulolinear collagenoma.

PMID- 16631955
TI  - Nicolau's syndrome in a newborn caused by triple DTP (diphtheria-tetanus
      pertussis) vaccination.

PMID- 16631956
TI  - Efalizumab-induced subacute cutaneous lupus erythematosus.

PMID- 16631957
TI  - Topical clindamycin reproducibly causing tinnitus in a 14-year-old boy.

PMID- 16631958
TI  - Recurrent pyogenic granuloma treated with topical imiquimod.

PMID- 16631959
TI  - Generalized granuloma annulare treated with short-term administration of
      etretinate.

PMID- 16631960
TI  - Vesiculopustules in adult-onset Still's disease.

PMID- 16631961
TI  - Trastuzumab-induced cytoplasmic anti-neutrophilic cytoplasmic antibody
      necrotizing granulomatous panniculitis.

PMID- 16631962
TI  - Clear cell hidradenoma.

PMID- 16631963
TI  - Ionizing radiation-induced pemphigus foliaceus.

PMID- 16631964
TI  - VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic
      isolates of Plasmodium falciparum.
AB  - Malaria during pregnancy causes serious disease that is associated with
      sequestration in the placenta of Plasmodium falciparum infected erythrocytes that
      adhere to several host receptors, including chondroitin sulfate A (CSA). The
      principal CSA binding ligand associated with placental sequestration is the P.
      falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var2csa gene.
      We disrupted the var2csa gene in two allogeneic parasites and ablated CSA
      binding. However, in one parasite line we were able to re-select for adhesion to
      bovine trachea CSA associated with transcription of two var genes, var-CS2 and
      varP. Parasites transcribing parts of var-CS2 and varP were present in the
      placentae of some infected women but the mutant parasites that transcribed var
      CS2 and varP were recognized by sera from men and pregnant women independent of
      parity. This work raises the possibility that the PfEMP1 molecules encoded by var
      CS2 and varP may be minor contributors to placental malaria but also confirms the
      importance of the immunodominant, conserved var2csa PfEMP1s in pregnancy
      associated malaria and strengthens the case for var2csa as a pregnancy-specific
      malaria vaccine.

PMID- 16631966
TI  - Increasing our understanding of pigmentary disorders.
AB  - This article focuses on developments in pigmentary disorders that extend
      dermatologists' understanding of the field. Areas that are reviewed include the
      basic biochemistry, pharmacology, and physiology of the melanocortin system;
      melanosome development; genetic diseases associated with pigmentary disorders;
      pigmentary disorders secondary to systemic disease; drug-induced
      hyperpigmentation; environmental exposure to chemicals; and primary disorders of
      hyperpigmentation such as melasma and lentigines. Basic, clinical, and
      epidemiological research, along with a number of clinical case reports, were
      included in the review. This article also reports on the new health-related
      quality-of-life instrument (MELASQOL) that has been developed for women with
      melasma.

PMID- 16631967
TI  - Treatment of solar lentigines.
AB  - Therapy for solar lentigines is diverse but can be divided into two broad
      categories: physical therapy and topical therapy. Physical therapies are
      frequently used with excellent clinical success rates, but this has to be
      balanced against associated side effects and recurrence rates with certain
      therapies. A range of topical therapies have been used and, more recently, fixed
      combinations of topical agents have been investigated. The Pigmentary Disorders
      Academy undertook to evaluate the clinical efficacy of the different treatments
      of solar lentigines in order to generate a consensus statement on their
      management. Clinical papers published during the past 20 years were identified
      through MEDLINE searches and methodology and outcome were assessed according to
      guidelines adapted from the US Preventive Services Task Force (USPSTF) on health
      care. The consensus of the group was that first-line therapy for solar lentigines
      was ablative therapy with cryotherapy. Although no large-scale studies have been
      completed, there is also good evidence to suggest that lasers are an effective
      treatment. An alternative to ablative therapy is topical therapy and there is
      good evidence to support the use of a fixed double combination, as well as
      retinoids, such as adapalene and tretinoin. Topical therapy can also be
      considered as maintenance therapy after the primary therapy has been applied.
      Because of the diversity of scoring systems used in the assessment of treatment
      outcome, the group recommends the development of treatment guidelines.

PMID- 16631968
TI  - Treatment of melasma.
AB  - Treatment of melasma involves the use of a range of topical depigmenting agents
      and physical therapies. Varying degrees of success have been achieved with these
      therapies. The Pigmentary Disorders Academy (PDA) undertook to evaluate the
      clinical efficacy of the different treatments of melasma in order to generate a
      consensus statement on its management. Clinical papers published during the past
      20 years were identified through MEDLINE searches and methodology and outcome
      assessed according to guidelines adapted from the US Preventive Services Task
      Force (USPSTF). The consensus of the group was that first-line therapy for
      melasma should consist of effective topical therapies, mainly fixed triple
      combinations. Where patients have either sensitivity to the ingredients or a
      triple combination therapy is unavailable, other compounds with dual ingredients
      (hydroquinone plus glycolic acid) or single agents (4% hydroquinone, 0.1%
      retinoic acid, or 20% azelaic acid) may be considered as an alternative. In
      patients who failed to respond to therapy, options for second-line therapy
      include peels either alone or in combination with topical therapy. Some patients
      will require therapy to maintain remission status and a combination of topical
      therapies should be considered. Lasers should rarely be used in the treatment of
      melasma and, if applied, skin type should be taken into account.

PMID- 16631969
TI  - Noninvasive techniques for the evaluation of skin color.
AB  - Visual assessment remains one of the "gold standard" methods of assessing skin
      color and a number of tools are currently available to reduce the interobserver
      variability. Ultraviolet light examination remains a mainstay of the assessment
      of pigmentary disorders, while polarized light photography is useful for the
      appraisal of dermal changes, in particular those related to vascularity. With the
      introduction of modern instruments, reflectance spectroscopy using tristimulus
      colorimeters or narrowband spectrophotometers provides a convenient, objective,
      and reproducible methodology for the evaluation of pigmentation and skin color.
      In vivo confocal scanning laser microscopy is a powerful technique for the
      examination of pigmented lesions, which shows promise in the detection and
      diagnosis of early melanoma. Dermoscopy is also useful for the differential
      diagnosis of benign melanocytic lesions and melanoma, and its use has been shown
      to significantly improve diagnostic accuracy.

PMID- 16631970
TI  - Confusions about color: formulating a more precise lexicon for pigmentation,
      pigmentary disorders, and abnormalities of "chromatics".

PMID- 16631971
TI  - Copper trafficking to the mitochondrion and assembly of copper metalloenzymes.
AB  - Copper is required within the mitochondrion for the function of two
      metalloenzymes, cytochrome c oxidase (CcO) and superoxide dismutase (Sod1).
      Copper metallation of these two enzymes occurs within the mitochondrial
      intermembrane space and is mediated by metallochaperone proteins. Cox17 is a key
      copper donor to two accessory proteins, Sco1 and Cox11, to form the two copper
      centers in the mature CcO complex. Ccs1 is the necessary metallochaperone for the
      copper metallation of Sod1 in the IMS as well as within the cytoplasm where the
      bulk of Sod1 resides. Copper ions used in the metallation of CcO and Sod1 appear
      to be provided by a novel copper pool within the mitochondrial matrix. This
      review documents copper ion shuttling within the mitochondrion and the proteins
      that mediate assembly of active CcO and Sod1.

PMID- 16631972
TI  - Efficacy of monensin sodium for the reduction of fecal shedding of Mycobacterium
      avium subsp. paratuberculosis in infected dairy cattle.
AB  - Reducing the quantity of Mycobacterium avium subsp. paratuberculosis (MAP) being
      shed by cows with Johne's disease should decrease the risk of spread of this
      disease to young stock. Previous work has suggested that monensin sodium
      decreases the pathologic lesions associated with Johne's disease, but the impact
      on shedding of viable MAP remains unknown. After serologic screening of 32 dairy
      herds in southwestern Ontario, 228 cows from 13 of these herds were enrolled into
      a randomized clinical trial. Fecal culture and PCR were used to identify 114 cows
      as potential fecal shedders, while another 114 cows were enrolled as ELISA
      negative, herd and parity matched controls. All cows were randomized to receive
      either a monensin controlled release capsule (CRC) or a placebo capsule. Serial
      fecal and blood samples were collected for fecal culture and serum ELISA testing
      over a 98-day period. On day 98 of the study, treatments were switched for all
      cows continuing in the trial. These remaining cows were followed for another 98
      days with a similar sampling protocol. Mixed effect models were used to measure
      the impact of treatment on the number of colony forming units identified on fecal
      cultures over time. During the first 98 days of the study, cows treated with a
      monensin CRC were found to shed 3.4cfu per tube less than placebo treated cows
      (P=0.05). The serum ELISA S/P ratio was reduced by 1.39 units in cows given
      monensin (P=0.06). However, treatment with monensin did not reduce the odds of
      testing positive on serology. Only the cows shedding MAP on day 0 were found to
      have a reduced odds of testing positive on fecal culture when treated with
      monensin (OR=0.27; P=0.03). Monensin sodium administered to infected animals at
      335mg/day marginally reduced fecal shedding of MAP in mature dairy cattle, but
      the biological significance of this reduction is unknown.

PMID- 16631973
TI  - Is there evidence to support the need for routine surgeon presence on trauma
      patient arrival?
AB  - The trauma center certification requirements of the American College of Surgeons
      include the expectation that, whenever possible, general surgeons be routinely
      present at the emergency department arrival of seriously injured patients. The 2
      historical factors that originally prompted this requirement, frequent
      exploratory laparotomies and emergency physicians without trauma training, no
      longer exist in most modern trauma centers. Research from multiple centers and in
      multiple varying formats has not identified improvement in patient-oriented
      outcomes from early surgeon involvement. Surgeons are not routinely present
      during the resuscitative phase of Canadian and European trauma care, with no
      demonstrated or perceived decrease in the quality of care. American trauma
      surgeons themselves do not consistently believe that their use in this capacity
      is either necessary or an efficient distribution of resources. There is not
      compelling evidence to support the assumption that trauma outcomes are improved
      by the routine presence of surgeons on patient arrival. Research is necessary to
      clarify which trauma patients require either emergency or urgent unique expertise
      of a general surgeon during the initial phase of trauma management. Individual
      trauma centers should be permitted the flexibility necessary to perform such
      research and to use such findings to refine and focus their secondary triage
      criteria.

PMID- 16631974
TI  - Images in emergency medicine. Visual diagnosis: a painful rash.

PMID- 16631975
TI  - Role of the acute care surgeon in the emergency department management of trauma.

PMID- 16631976
TI  - A pilot study to derive clinical variables for selective chest radiography in
      blunt trauma patients.
AB  - STUDY OBJECTIVE: The goal of this pilot study was to determine whether clinical
      criteria can identify blunt trauma patients with significant acute intrathoracic
      injury on chest radiograph. METHODS: From January 2003 to May 2004, adult blunt
      trauma patients who received chest radiographs were prospectively enrolled at 2
      urban trauma centers. Exclusion criteria were age less than 15 years, penetrating
      trauma, trauma more than 72 hours before presentation, isolated head trauma, and
      Glasgow Coma Scale score less than 14. Before chest radiograph viewing, providers
      recorded the following data: mechanism of injury, vital signs including oxygen
      saturation, patient symptoms, intoxication, distracting injuries, and the
      presence or finding of visible chest wall injury, chest palpation tenderness,
      pain on lateral chest compression, crepitus, and abnormal chest auscultation.
      Significant acute intrathoracic injury was defined as pneumothorax, hemothorax,
      aortic injury, 2 or more rib fractures, sternal fracture, or pulmonary contusion
      by blinded radiologist chest radiograph interpretation. RESULTS: Of the 507
      enrolled patients, 15 patients were excluded because chest radiograph was not
      performed. Significant acute intrathoracic injury was confirmed in 31 of 492
      (6.3%) patients. Palpation tenderness and chest pain had the highest sensitivity
      (90%) as individual criteria for significant acute intrathoracic injury, and
      hypoxia had the highest specificity (97%). The combination of palpation
      tenderness and hypoxia identified all significant acute intrathoracic injury with
      the following screening performance with 95% confidence intervals (CIs):
      sensitivity 100% (95% CI 91% to 100%); specificity 50% (95% CI 45% to 54%);
      positive predictive value 12% (95% CI 9% to 17%); and negative predictive value
      100% (95% CI 99% to 100%). CONCLUSION: In this small sample, the combination of
      palpation tenderness and hypoxia identified all blunt trauma patients with
      significant acute intrathoracic injury while potentially eliminating the need for
      46% of chest radiographs.

PMID- 16631977
TI  - Imaging in trauma.

PMID- 16631978
TI  - Selective chest radiography in blunt trauma: who cares?

PMID- 16631980
TI  - Chest radiography in blunt trauma patients: is it necessary?

PMID- 16631981
TI  - Use of 2-octyl cyanoacrylate for the repair of a fractured molar tooth.
AB  - Odontalgia in association with an acutely fractured tooth is a frequent reason
      for emergency department presentation. We describe the case of a patient who
      presented with a painful fractured molar tooth and was treated with topical
      application of 2-octyl cyanoacrylate tissue adhesive, resulting in prompt relief
      of her discomfort and a good temporary functional and cosmetic outcome. This
      product may prove useful in treating similar dental emergencies when access to
      emergency dental care is unavailable.

PMID- 16631982
TI  - A critical pathway for patients with acute chest pain and low risk for short-term
      adverse cardiac events: role of outpatient stress testing.
AB  - STUDY OBJECTIVE: We evaluate the safety and feasibility of a critical care
      pathway protocol in which patients with acute chest pain who are low risk for
      coronary artery disease and short-term adverse cardiac outcomes receive
      outpatient stress testing within 72 hours of an emergency department (ED) visit.
      METHODS: We performed an observational study of an ED-based chest pain critical
      pathway in an urban, community hospital in 979 consecutive patients. Patients
      enrolled in the protocol were observed in the ED before receiving 72-hour
      outpatient stress testing. The pathway was primarily analyzed for rates of death
      or myocardial infarction in the 6 months after ED discharge and outpatient stress
      testing. Secondary outcome measures included need for coronary intervention at
      initial stress testing and within 6 months after discharge, subsequent ED visits
      for chest pain, and subsequent hospitalization. RESULTS: Of 871 stress-tested
      patients aged 40 years or older, who had low risk for coronary artery disease and
      short-term adverse cardiac events, and had 6-month follow-up, 18 (2%) required
      coronary intervention, 1 (0.1%) had a myocardial infarction within 1 month, 2
      (0.2%) had a myocardial infarction within 6 months, 6 (0.7%) had normal stress
      test results after discharge but required cardiac catheterization within 6
      months, and 5 (0.6%) returned to the ED within 6 months for ongoing chest pain.
      Hospital admission rates decreased significantly from 31.2% to 26.1% after
      initiation of the protocol (P<.001). CONCLUSION: For patients with chest pain and
      low risk for short-term cardiac events, outpatient stress testing is feasible,
      safe, and associated with decreased hospital admission rates. With an evidence
      based protocol, physicians efficiently identify patients at low risk for
      clinically significant coronary artery disease and short-term adverse cardiac
      outcomes.

PMID- 16631983
TI  - Stress testing: it is safe to wait.

PMID- 16631984
TI  - Prospective multicenter study of quantitative pretest probability assessment to
      exclude acute coronary syndrome for patients evaluated in emergency department
      chest pain units.
AB  - STUDY OBJECTIVE: We compare the diagnostic accuracy of 3 methods--attribute
      matching, physician's written unstructured estimate, and a logistic regression
      formula (Acute Coronary Insufficiency-Time Insensitive Predictive Instrument, ACI
      TIPI)--of estimating a very low pretest probability (< or = 2%) for acute
      coronary syndromes in emergency department (ED) patients evaluated in chest pain
      units. METHODS: We prospectively studied 1,114 consecutive patients from 3
      academic EDs, evaluated for acute coronary syndrome. Physicians collected data
      required for pretest probability assessment before protocol-driven chest pain
      unit testing. A pretest probability greater than 2% was considered "test
      positive." The criterion standard was the outcome of acute coronary syndrome
      (death, myocardial infarction, revascularization, or > 60% stenosis prompting new
      treatment) within 45 days, adjudicated by 3 independent reviewers. RESULTS: Fifty
      one of 1,114 enrolled patients (4.5%; 95% confidence interval [CI] 3.4% to 6.0%)
      developed acute coronary syndrome within 45 days, including 4 of 991 (0.4%; 95%
      CI 0.1% to 1.0%) patients, discharged after a negative chest pain unit evaluation
      result, who developed acute coronary syndrome. Unstructured estimate identified
      293 patients with pretest probability less than or equal to 2%, 2 had acute
      coronary syndrome, yielding sensitivity of 96.1% (95% CI 86.5% to 99.5%) and
      specificity of 27.4% (95% CI 24.7% to 30.2%). Attribute matching identified 304
      patients with pretest probability less than or equal to 2%; 1 had acute coronary
      syndrome, yielding a sensitivity of 98.0% (95% CI 89.6% to 99.9%) and a
      specificity of 26.1% (95% CI 23.6% to 28.7%). ACI-TIPI identified 56 patients;
      none had acute coronary syndrome, yielding sensitivity of 100% (95% CI 93.0% to
      100%) and specificity of 6.1% (95% CI 4.7% to 7.9%). CONCLUSION: In a low-risk ED
      population with symptoms suggestive of acute coronary syndrome, patients with a
      quantitative pretest probability less than or equal to 2%, determined by
      attribute matching, unstructured estimate, or logistic regression, may not
      require additional diagnostic testing.

PMID- 16631985
TI  - Prospective validation of the San Francisco Syncope Rule to predict patients with
      serious outcomes.
AB  - STUDY OBJECTIVE: We prospectively validate the San Francisco Syncope Rule
      (history of congestive heart failure, Hematocrit <30%, abnormal ECG result [new
      changes or non-sinus rhythm], complaint of shortness of breath, and systolic
      blood pressure <90 mm Hg during triage). METHODS: In a prospective cohort study,
      consecutive patients with syncope or near syncope presenting to an emergency
      department (ED) of a teaching hospital were identified and enrolled from July 15,
      2002, to August 31, 2004. Patients with trauma, alcohol, or drug-associated loss
      of consciousness and definite seizures were excluded. Physicians prospectively
      applied the San Francisco Syncope Rule after their evaluation, and patients were
      followed up to determine whether they had had a predefined serious outcome within
      30 days of their ED visit. RESULTS: Seven hundred ninety-one consecutive visits
      were evaluated for syncope, representing 1.2% of all ED visits. The average age
      was 61 years, 54% of patients were women, and 59% of patients were admitted.
      Fifty-three visits (6.7%) resulted in patients having serious outcomes that were
      undeclared during their ED visit. The rule was 98% sensitive (95% confidence
      interval [CI] 89% to 100%) and 56% specific (95% CI 52% to 60%) to predict these
      events. In this cohort, the San Francisco Syncope Rule classified 52% of the
      patients as high risk, potentially decreasing overall admissions by 7%. If the
      rule had been applied only to the 453 patients admitted, it might have decreased
      admissions by 24%. CONCLUSION: The San Francisco Syncope Rule performed with high
      sensitivity and specificity in this validation cohort and is a valuable tool to
      help risk stratify patients. It may help with physician decisionmaking and
      improve the use of hospital admission for syncope.

PMID- 16631986
TI  - Prospective validation of the San Francisco Syncope Rule: will it change
      practice?

PMID- 16631987
TI  - Nonprescription availability of emergency contraception in the United States:
      current status, controversies, and impact on emergency medicine practice.
AB  - In October 2004, the American College of Emergency Physicians Council joined more
      than 60 other health professional organizations in supporting the nonprescription
      availability of emergency contraception. This article reviews the history,
      efficacy, and safety of emergency contraception; the efforts toward making
      emergency contraception available without a prescription in the United States;
      the arguments for and against nonprescription availability of emergency
      contraception; and the potential impact nonprescription availability could have
      on the practice of emergency medicine in the United States.

PMID- 16631988
TI  - Pneumonitis and eosinophilia after in vitro fertilization treatment.
AB  - A 33-year-old woman presented to the emergency department (ED) with tachypnea,
      tachycardia, and hypoxia, complaining of dyspnea and paroxysms of dry cough for 2
      days. The patient had undergone an unsuccessful in vitro fertilization procedure
      1 month earlier and had had another embryo implantation 6 days earlier. She had
      been receiving intramuscular injections of estradiol and progesterone in sesame
      oil to support implantation. A chest radiograph demonstrated extensive bilateral
      pulmonary consolidation; a leukocytosis count of 19.7 x 10(9) with 20%
      eosinophils was noted on a CBC count. A MEDLINE search yielded a case report in
      infertility literature describing an eosinophilic pneumonitis with similar
      clinical features after injections of progesterone in sesame oil. Treatment with
      intravenous corticosteroids was initiated in the ED, resulting in symptom and
      chest radiograph result improvement within 2 days and sparing the patient further
      imaging and antibiotic therapy.

PMID- 16631989
TI  - Report of the Task Force on Residency Training Information (2005-2006), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residency training programs and the residents training in
      those programs. We present the ninth annual report on the status of US emergency
      medicine residency programs.

PMID- 16631991
TI  - Images in emergency medicine. Ludwig's angina in a 4 month old infant.

PMID- 16631992
TI  - Response to: To dive or not to dive? Use of hyperbaric oxygen therapy to prevent
      neurologic sequelae in patients acutely poisoned with carbon monoxide.

PMID- 16631994
TI  - JCAHO/CMS core measures for community-acquired pneumonia.

PMID- 16631995
TI  - The use of a D-dimer as a screening test in the emergency department.

PMID- 16631999
TI  - Availability of hospital diagnostic and therapeutic services.

PMID- 16632000
TI  - Non-discrimination.

PMID- 16632001
TI  - EMS communication network.

PMID- 16632002
TI  - Health courts.

PMID- 16632003
TI  - Artificial neural network based identification of Campylobacter species by
      Fourier transform infrared spectroscopy.
AB  - Two prototypes of artificial neural network (ANN), multilayer perceptron (MLP),
      and probabilistic neural network (PNN), were used to analyze infrared (IR)
      spectral data obtained from intact cells belonging to the species Campylobacter
      coli and Campylobacter jejuni. In order to establish a consistent identification
      and typing procedure, mid infrared spectra of these species were obtained by
      means of a Fourier transform infrared (FT-IR) spectroscope. FT-IR patterns
      belonging to 26 isolates subclassified into 4 genotypes were pre-processed
      (normalized, smoothed and derivatized) and grouped into training, verification
      and test sets. The two architectures tested (PNN, MLP) were developed and trained
      to identify or leave unassigned a number of IR patterns. Two window ranges (w(4),
      1200 to 900 cm(-1); and w(5), 900 to 700 cm(-1)) in the mid IR spectrum were
      presented as input to the ANN models functioning as pattern recognition systems.
      No matter the ANN used all the training sets were correctly identified at
      subspecies level. For the test set, the four-layer MLP network was found to be
      specially suitable to recognize FT-IR data since it correctly identified 99.16%
      of unknowns using the w(4) range, and was fully successful in detecting atypical
      patterns from closely related Campylobacter strains and other bacterial species.
      The PNN network obtained lower percentages in assignation and rejection. Overall,
      ANNs constitute an excellent mathematical tool in microbial identification, since
      they are able to recognize with a high degree of confidence typical as well as
      atypical FT-IR fingerprints from Campylobacter spp.

PMID- 16632004
TI  - A fermentation assay to evaluate the effectiveness of antimicrobial agents on gut
      microflora.
AB  - The measurement of gas produced as a fermentation end product in vitro was
      correlated with absorbance as a measure of bacterial growth and was used as a
      rapid screening procedure to test the antimicrobial activity of certain essential
      oil and tannin secondary plant metabolites on gastrointestinal microorganisms
      from chickens. The assay was optimised using Clostridium perfringens and
      Lactobacillus fermentum, and tested in antimicrobial assays against C.
      perfringens; the minimum inhibitory concentration for each essential oil and
      condensed tannin was determined. The effect of penicillin-G on C. perfringens, in
      both growth and fermentation assays, was similar, and for all secondary
      metabolites tested, concentrations that inhibited fermentation were also
      bacteriocidal. The assay was also used to demonstrate the effect of dietary
      composition and enzyme supplementation on fermentation of mixed gut microflora in
      vitro; results are compared with in vivo results for the same dietary treatments.
      The data demonstrate that the effects of bioactive secondary plant products and
      feed composition on individual organisms or mixed gut microflora can be tested by
      analysis of fermentative activity in vitro, and that this provides a rapid assay
      for testing potential poultry feed additives before in vivo trials.

PMID- 16632005
TI  - Preservation of micro-organisms by drying; a review.
AB  - The preservation of micro-organisms by different drying methodologies has been
      used for decades. Freeze drying in particular is the preferred method for
      transporting and storing vast culture collections of micro-organism strain types.
      The literature on drying and preserving micro-organisms is extensive, but is
      often specific to one particular strain. This review attempts to draw some
      similar concepts and findings together in one paper, to compare different drying
      techniques, with specific reference to microorganisms. The main topics covered
      are cell growth phases and concentration, inducing drying tolerance in microbial
      cells, drying methods, rehydration of dried cells and packaging and storage
      conditions. Also, particular attention has been paid to the use of freeze drying
      and the protective matrices used to improve microbial cell viability after
      drying.

PMID- 16632006
TI  - Control of nodal metastases in squamous cell head and neck cancer treated by
      radiation therapy or chemoradiation.
AB  - BACKGROUND AND PURPOSE: In the present study, prognostic values of several CT
      based pre-treatment nodal and treatment-related characteristics were evaluated
      among patients with squamous cell head and neck cancer treated with non-surgical
      modalities. PATIENTS AND METHODS: Included were 79 patients with 210 pathological
      nodes, who underwent primary irradiation or chemoradiation. Several nodal
      characteristics were assessed on the planning CT scan. In addition, the 3D-dose
      distribution in the nodes was calculated by the planning system to allow for
      evaluation of underdosage in the pathological nodes and to correlate these
      results with control in the neck. Analysis was done on patient level (regional
      control) and node level (nodal control). RESULTS: For regional control, total
      nodal volume and the use of chemotherapy in addition to radiation were
      significant prognostic factors. For nodal control, also the presence of central
      necrosis and radiological extranodal spread were of importance. In case of
      radiotherapy alone, a minimal dose <95% of the prescribed dose was associated
      with worse control. In case of combined modality treatment, the minimal radiation
      dose was of less importance. CONCLUSIONS: Nodal volume and chemotherapy are the
      most important prognostic factors to control pathological nodes in the neck.
      Radiological central necrosis and extranodal growth, nodal volume and
      chemotherapy were significant prognostic factors for nodal control. Additionally,
      it appears that regional control in patients treated with primary radiation alone
      or with chemoradiation in case of a total nodal volume of more than 3.0 cm(3)
      results in an unacceptable high risk on regional recurrence.

PMID- 16632007
TI  - Asthma self-efficacy, high frequency heart rate variability, and airflow
      obstruction during negative affect in daily life.
AB  - BACKGROUND: Emotional stress has been considered an important asthma trigger for
      years, though the mechanisms by which stress may exacerbate asthma remain poorly
      understood. The stress-asthma morbidity association could occur through cognitive
      behavioral pathways, such as decreased asthma self-efficacy and disorganized self
      care, or through the more direct physiological effects of stress on autonomic
      (parasympathetic) nervous system activity. No study has examined how these two
      mechanisms may interact to contribute to greater airflow obstruction during
      emotional stress in daily life. This study investigated associations between peak
      expiratory flow rate (PEFR) and high frequency heart rate variability (HFHRV)
      during periods of negative affect and physical activity in daily life in patients
      with higher versus lower asthma self-efficacy scores. METHODS: Fifty-three
      patients with mild to moderate asthma completed the Asthma Self-Efficacy Scale
      (ASES) and underwent a 15 h ambulatory assessment of daytime HFHRV and PEFR,
      while completing self-report diaries of their physical activities and affect.
      RESULTS: In patients with lower asthma self-efficacy scores, increased levels of
      negative affect during daily life were associated with higher levels of HFHRV and
      decreased PEFR relative to patients with higher asthma self-efficacy scores.
      Increased levels of physical activity were associated with decreased levels of
      HFHRV irrespective of asthma self-efficacy scores. CONCLUSIONS: Findings suggest
      that lower asthma self-efficacy may be associated with increased parasympathetic
      activity and airflow obstruction during periods of negative affect during daily
      life.

PMID- 16632008
TI  - Isolated Brucella peritonitis in a CAPD patient.
AB  - Peritonitis is the most common complication in patients undergoing continuous
      ambulatory peritoneal dialysis (CAPD). Brucellosis is a rare cause of bacterial
      peritonitis. Only 1 case was reported of a patient with brucella peritonitis
      during CAPD therapy. In that case, CAPD peritonitis was accompanied by acute
      brucellosis. We present the case of a patient with isolated brucella peritonitis
      receiving CAPD therapy without systemic manifestations of brucellosis who works
      as a farmer. Results of a serum agglutination test and blood cultures were
      negative; however, the patient's peritoneal fluid agglutination titer was 1:160
      and samples inoculated into BACTEC (Becton Dickinson, NJ) bottles yielded
      Brucella melitensis. Because we were unable to isolate the organism in blood
      samples, transmission seems to be the result of direct inoculation, rather than
      hematogenous spreading. Therefore, our patient represents the first case of
      isolated brucella peritonitis during CAPD therapy. Successful treatment was
      obtained by using a treatment regimen of rifampin and doxycycline.

PMID- 16632009
TI  - Sirolimus-induced remission of posttransplantation lymphoproliferative disorder.
AB  - Posttransplantation lymphoproliferative disorder (PTLD) is one of the most
      serious complications of solid-organ transplantation. It potentially is treatable
      in most cases, but current methods involve withdrawal or reduction of
      immunosuppression and the consequent risk for graft rejection. Sirolimus was
      shown in vivo and in vitro to limit proliferation of a number of malignant cell
      lines, including those of PTLD-derived cells. We present a case of disseminated
      PTLD in a patient with a renal transplant that resolved completely with
      conversion of immunosuppression to sirolimus. Graft function was maintained and
      improved with treatment. This offers a novel means of treating these patients and
      minimizing transplant loss.

PMID- 16632010
TI  - Meta-analysis of biochemical and patient-level effects of calcimimetic therapy.
AB  - BACKGROUND: Many randomized trials have now evaluated the effects of
      calcimimetics in patients with chronic kidney disease and secondary
      hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate
      binders. We conducted a meta-analysis to evaluate outcomes of therapy with these
      novel agents. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register,
      and conference proceedings were searched for randomized controlled trials
      evaluating any calcimimetic against placebo or another agent in predialysis or
      dialysis patients with chronic kidney disease. Data were extracted for all
      relevant patient-centered and surrogate outcomes. Analysis was by means of a
      random-effects model, and results are expressed as relative risk or weighted mean
      difference (WMD) with 95% confidence intervals (CIs). RESULTS: Eight trials
      (1,429 patients) were identified that compared a calcimimetic agent plus standard
      therapy with placebo plus standard therapy. End-of-treatment values for
      parathyroid hormone (4 trials; 1,278 patients; WMD, -290.49 pg/mL; 95% CI, 
      359.91 to -221.07), serum calcium (3 trials; 1,201 patients; WMD, -0.85 mg/dL;
      95% CI, -1.14 to -0.56), serum phosphorus (3 trials; 1,195 patients; WMD, -0.29
      mg/dL; 95% CI, -0.50 to -0.08), and calcium x phosphorus product (3 trials; 1,194
      patients; WMD, -7.90 mg2/dL2; 95% CI, -10.25 to -5.54) were significantly lower
      with calcimimetic therapy compared with placebo. No significant effects on
      patient-based end points were shown. CONCLUSION: Calcimimetic treatment of
      patients with SHPT leads to significant improvements in biochemical parameters
      that observational studies have associated with increased mortality,
      cardiovascular risk, and osteitis fibrosa, but patient-based benefits have not
      yet been shown. For patients with SHPT, the benefits of calcimimetics over
      standard therapy remain uncertain until additional randomized trials become
      available.

PMID- 16632011
TI  - Vasopressin excess and hyponatremia.
AB  - Hyponatremia is a common electrolyte disorder that frequently is overlooked and
      undertreated. Although the pathophysiological process of hyponatremia is complex,
      arginine vasopressin (AVP) is a common etiologic factor. Excess AVP release by
      osmotic or nonosmotic stimuli or both can lead to sodium and water imbalance.
      Conventional treatment options for hyponatremia, including water restriction and
      administration of sodium chloride with or without loop diuretics, do not directly
      address the underlying water retention induced by excess AVP in many cases.
      Clinical trials showed that AVP-receptor antagonists, including lixivaptan,
      tolvaptan, and conivaptan, produce aquaresis, the electrolyte-sparing excretion
      of free water, to correct serum sodium concentration. We review results from
      recent clinical trials involving AVP-receptor antagonists in the treatment of
      hyponatremia associated with AVP excess.

PMID- 16632012
TI  - Effect of early correction of anemia on the progression of CKD.
AB  - BACKGROUND: This study is designed to assess the effect of early and complete
      correction of anemia by using recombinant human erythropoietin (epoetin) alfa on
      the progression of chronic kidney disease (CKD). METHODS: Patients were randomly
      assigned to achieve high (13 to 15 g/dL [130 to 150 g/L]) or low (11 to 12 g/dL
      [110 to 120 g/L]) hemoglobin-level targets during 4 months of stabilization,
      followed by 36 months of maintenance. Glomerular filtration rate (GFR) decrease
      was measured by using iohexol clearance. Quality of life, nutrition, and safety
      also were monitored. RESULTS: Because of labeling changes for subcutaneous
      administration of epoetin alfa (Eprex; Johnson and Johnson, Schaffhausen,
      Switzerland), the study was terminated prematurely. There were 195 patients
      enrolled in each group; 108 high-hemoglobin and 133 low-hemoglobin patients
      entered the maintenance phase. Mean maintenance duration was 7.4 months for the
      high-hemoglobin group and 8.3 months for the low-hemoglobin group. GFR decrease
      was numerically, but not statistically significantly, lower with the high
      hemoglobin group (0.058 versus 0.081 mL/min/1.73 m2/mo [< 0.01 mL/s/1.73 m2/mo]).
      Physical quality-of-life measures showed trends (Role-Physical, P = 0.055;
      Physical Function, P = 0.083) or statistically significant improvement (Vitality,
      P = 0.042) with high hemoglobin levels at the end of the stabilization phase.
      Adverse events were similar between groups. Cardiovascular adverse events
      occurred in 25% of the high-hemoglobin and 18% of the low-hemoglobin patients (P
      = 0.137). Neither epoetin dosage nor hemoglobin level was associated with
      cardiovascular adverse events or death. CONCLUSION: These data suggest that
      normalization of hemoglobin levels in patients with CKD is safe. Longer duration
      studies are needed to clarify efficacy benefits with high hemoglobin levels.

PMID- 16632013
TI  - Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind,
      randomized, placebo-controlled study.
AB  - BACKGROUND: Previous studies showed that angiotensin-receptor blocker (ARB)
      therapy decreased proteinuria and possibly slowed the rate of renal function
      decline in patients with chronic proteinuric nephropathies. We performed a double
      blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in
      the treatment of patients with immunoglobulin A (IgA) nephropathy. METHODS: From
      6 centers, we recruited 109 patients with IgA nephropathy who had either: (1)
      proteinuria with protein greater than 1 g/d and serum creatinine level less than
      2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL
      (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were
      randomly assigned to administration of either valsartan, 80 mg/d (titrated up to
      160 mg/d for blood pressure control), or placebo for 104 weeks. Additional
      antihypertensive therapy was allowed to achieve a target blood pressure of 140/90
      mm Hg. The primary end point was doubling of serum creatinine level or dialysis
      dependent renal failure. Secondary outcomes included change in proteinuria and
      decrease in glomerular filtration rate (GFR). RESULTS: There were 54 patients in
      the treatment group and 55 patients in the placebo group. Baseline clinical
      characteristics were similar between groups, although the treatment group had a
      marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45
      +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria
      (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group.
      Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the
      treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During
      the study period, 4 patients in the placebo group and 1 patient in the treatment
      group reached the primary end point (log-rank test, P = 0.18). Proteinuria
      decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/-
      1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear
      regression models, valsartan treatment resulted in a 33.0% decrease in
      proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other
      confounding factors. There was a significant decrease in mean rate of GFR
      decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11
      mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10
      mL/s/y]) throughout the study period after adjustment for average blood pressure
      and proteinuria (P = 0.014). CONCLUSION: Valsartan significantly decreases
      proteinuria and slows renal deterioration in patients with IgA nephropathy after
      adjustment for confounding factors, notably blood pressure. The long-term benefit
      of valsartan needs to be confirmed with additional studies.

PMID- 16632014
TI  - IgA nephropathy: the presence of familial disease does not confer an increased
      risk for progression.
AB  - BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common form of
      glomerulonephritis worldwide. Familial and sporadic cases are recognized, and a
      locus associated with the familial form of the disease was mapped to chromosome
      6. Recent data suggest the familial IgA nephropathy form may have a poorer
      outcome than the sporadic form. METHODS: We tested the hypothesis of unequal
      survival rates between the 2 forms of disease by analyzing time from biopsy to
      end-stage renal disease in patients of Italian ancestry; 589 patients with
      sporadic and 96 patients with familial IgA nephropathy. RESULTS: Overall 10- and
      20-year renal survival probabilities of the cohort as a whole were 71% and 50%,
      respectively. Macroscopic hematuria was the modality of clinical presentation in
      51% of patients with familial IgA nephropathy and 39% of patients with sporadic
      IgA nephropathy. At univariable analysis, the sporadic form of IgA nephropathy
      was associated significantly with increased risk for renal death. However,
      patients with the sporadic form tended to be more hypertensive and diagnosed
      later, with signs of more advanced renal disease than those with familial disease
      at baseline. In the regression model, form of disease lost any independent
      effect. Only male sex, lower baseline glomerular filtration rate, greater
      proteinuria, and histopathologic score proved to be independent predictors of
      disease progression. Treatment with steroids or angiotensin-converting enzyme
      inhibitors was associated with improved outcomes. CONCLUSION: Our study does not
      confirm that familial IgA nephropathy has a worse prognosis than the sporadic
      form. The similar renal phenotype may support a common pathogenic mechanism
      underlying familial and sporadic IgA nephropathy.

PMID- 16632015
TI  - Renal involvement in Churg-Strauss syndrome.
AB  - BACKGROUND: Churg-Strauss syndrome (CSS) is a rare disorder characterized by
      asthma, eosinophilia, and systemic vasculitis. Renal involvement is not regarded
      as a prominent feature, and its prevalence and severity vary widely in published
      reports that usually refer to small series of selected patients. METHODS: We
      examined the prevalence, clinicopathologic features, and prognosis of renal
      disease in 116 patients with CSS. RESULTS: There were 48 men and 68 women with a
      mean age of 51.9 years (range, 18 to 86 years). Signs of renal abnormalities were
      present in 31 patients (26.7%). Rapidly progressive renal insufficiency was
      documented in 16 patients (13.8%); urinary abnormalities, 14 patients (12.1%);
      and chronic renal impairment, 1 patient. There were 3 additional cases of
      obstructive uropathy. Sixteen patients underwent renal biopsy, which showed
      necrotizing crescentic glomerulonephritis in 11 patients. Other diagnoses were
      eosinophilic interstitial nephritis, mesangial glomerulonephritis, and focal
      sclerosis. Antineutrophil cytoplasmic antibody (ANCA) was positive in 21 of 28
      patients (75.0%) with nephropathy versus 19 of 74 patients without (25.7%; P <
      0.001). In particular, all patients with necrotizing crescentic
      glomerulonephritis were ANCA positive. After a median follow-up of 4.5 years, 10
      patients died (5 patients with nephropathy) and 7 patients developed mild chronic
      renal insufficiency. Five-year mortality rates were 11.7% (95% confidence
      interval, 3.9 to 33.3) in patients with nephropathy and 2.7% (95% confidence
      interval, 0.7 to 10.7) in those without (P = 0.10). CONCLUSION: Renal
      abnormalities are present in about one quarter of patients with CSS. The
      prevailing picture is ANCA-associated necrotizing crescentic glomerulonephritis;
      however, other forms of nephropathy also may occur. Outcome and long-term follow
      up usually are good.

PMID- 16632016
TI  - Association of prevalent hypertension with 24-hour urinary excretion of calcium,
      citrate, and other factors.
AB  - BACKGROUND: The relation between hypertension and the urinary excretion of
      calcium, citrate, and other factors is unclear. It has been proposed that
      increased urinary calcium excretion is a central feature of essential
      hypertension. Metabolic acidosis also may be associated with hypertension and
      decreases urinary citrate levels. METHODS: To compare the urine composition of
      individuals with and without hypertension, we studied 24-hour urinary excretion
      of calcium, citrate, oxalate, uric acid, sodium, magnesium, potassium,
      phosphorus, and creatinine and pH in a subset of participants with and without
      nephrolithiasis in the Nurses' Health Study I (older women; N = 1,284), Nurses'
      Health Study II (younger women; N = 952), and the Health Professionals Follow-up
      Study (men; N = 788). Logistic regression models adjusted for age, weight,
      dietary intake, and urinary factors. RESULTS: In participants with and without
      nephrolithiasis, citrate was the only urinary factor consistently related to
      hypertension. Compared with those in the lowest quartile of urinary citrate
      excretion, multivariate odds ratios of prevalent hypertension in the highest
      quartile were 0.37 (95% confidence interval [CI], 0.24 to 0.55; P trend < 0.001)
      for older women, 0.54 (95% CI, 0.32 to 0.92; P trend = 0.03) for younger women,
      and 0.27 (95% CI, 0.16 to 0.45; P trend < 0.001) for men. Urinary calcium levels
      were not related consistently to hypertension. Excluding participants with single
      24-hour urine collections and those administered thiazide diuretics or
      angiotensin-converting enzyme inhibitors did not change the results. CONCLUSION:
      Lower urinary citrate excretion is associated independently with prevalent
      hypertension. Factors that regulate urinary citrate excretion may play a role in
      hypertension.

PMID- 16632017
TI  - Increased pulse wave velocity is associated with low creatinine clearance and
      proteinuria in a screened cohort.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a risk factor for future
      cardiovascular disease. Although pulse wave velocity (PWV), which reflects
      arterial stiffness, was increased in subjects with CKD, little is known regarding
      whether renal function is associated with PWV in a low-risk population and
      whether proteinuria and decreased renal function synergistically affect PWV.
      METHODS: Subjects are 3,387 persons (mean age, 52 years) who attended a health
      checkup program in Okinawa, Japan. We measured brachial-ankle PWV (baPWV) by
      using an automatic oscillometric method. Proteinuria was semiquantified by using
      the dipstick method. Creatinine clearance (CCr) was estimated by using the
      Cockcroft-Gault formula. RESULTS: baPWV was accelerated with increases in age,
      systolic blood pressure, fasting glucose level, and total cholesterol level; male
      sex; presence of proteinuria; and decrease in CCr. All these factors
      independently predicted baPWV in multiple regression analysis. When subjects were
      divided into 6 groups according to CCr of 90 or greater, 60 to 89, or 30 to 59
      mL/min (> or =1.50, 1.00 to 1.48, or 0.50 to 0.98 mL/s) and the absence or
      presence of proteinuria, baPWV, after adjustment for age, sex, and systolic blood
      pressure, increased in a stepwise fashion corresponding to decreases in CCr
      regardless of proteinuria, with the relationship exaggerated in the presence of
      proteinuria. CONCLUSION: Arterial stiffness increases with a decrease in renal
      function or with proteinuria independently of other risk factors.

PMID- 16632018
TI  - Risk factors for acute renal insufficiency induced by diuretics in patients with
      congestive heart failure.
AB  - BACKGROUND: In patients with congestive heart failure (CHF), continuous diuretic
      therapy may result in acute renal insufficiency (ARI). This study examines
      factors contributing to this complication. METHODS: We analyzed clinical data
      from 318 consecutive patients who were hospitalized for CHF. All were treated
      with diuretics and had echocardiography performed within 4 days of
      hospitalization. Systolic left ventricular (LV) dysfunction is defined as an
      ejection fraction less than 50%, and diastolic LV dysfunction, as an ejection
      fraction of 50% or greater in the presence of LV hypertrophy and a reversed E/A
      ratio. RESULTS: ARI, defined as a 25% increase in serum creatinine level,
      occurred in 110 patients (35%) after diuretic therapy. Risk factors for ARI on
      univariate analyses were older age, higher baseline serum creatinine level, lower
      baseline serum sodium level, lower mean arterial pressure (MAP) during diuretic
      therapy, and greater doses and longer duration of diuretic therapy. In
      multivariate analyses, ARI occurred more frequently in patients with systolic
      (40%) than diastolic dysfunction (28%). The use of digoxin in patients with
      systolic LV dysfunction was observed to decrease the risk for ARI by 61%,
      independent of other agents used for the treatment of patients with CHF.
      CONCLUSION: Age, baseline renal function and serum sodium concentration, MAP, and
      intensity of diuretic therapy can identify individuals at risk for ARI while
      receiving diuretic therapy for CHF. This complication is observed more often in
      individuals with systolic dysfunction, and its risk may be decreased with the use
      of digoxin.

PMID- 16632019
TI  - A randomized controlled trial of fludrocortisone for the treatment of
      hyperkalemia in hemodialysis patients.
AB  - BACKGROUND: Previous small uncontrolled studies suggested that fludrocortisone
      may significantly decrease serum potassium concentrations in hemodialysis
      patients, possibly through enhancement of colonic potassium secretion. The aim of
      this study is to evaluate the effect of oral fludrocortisone on serum potassium
      concentrations in hyperkalemic hemodialysis patients in an open-label randomized
      controlled trial. METHODS: Thirty-seven hemodialysis patients with predialysis
      hyperkalemia were randomly allocated to administration of either oral
      fludrocortisone (0.1 mg/d; n = 18) or no treatment (control; n = 19) for 3
      months. The primary outcome measure was midweek predialysis serum potassium
      concentration, which was measured monthly during the trial. Prospective power
      calculations indicated that the study had an 80% probability of detecting a
      decrease in serum potassium levels of 0.7 mEq/L (0.7 mmol/L). RESULTS: Baseline
      patient characteristics were similar, except for slightly longer total weekly
      dialysis hours in the fludrocortisone group (13.0 +/- 1.3 versus 12.1 +/- 1.0; P
      = 0.02). At the end of the study period, no significant changes in serum
      potassium concentrations were observed between the fludrocortisone and control
      groups (4.8 +/- 0.5 versus 5.2 +/- 0.7 mEq/L [mmol/L], respectively; P = 0.10).
      Similar results were obtained when changes in serum potassium levels over time
      were examined between the 2 arms by using repeated-measures analysis of variance,
      with or without adjustment for total weekly dialysis hours. Secondary outcomes,
      including predialysis mean arterial pressure, interdialytic weight gain, serum
      sodium level, and hospitalization for hyperkalemia, were not significantly
      different between groups. There were no observed adverse events. CONCLUSION:
      Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and
      well tolerated, but does not achieve clinically important decreases in serum
      potassium levels.

PMID- 16632020
TI  - Does periodontitis reflect inflammation and malnutrition status in hemodialysis
      patients?
AB  - BACKGROUND: Chronic infection and inflammation, including periodontitis, is
      linked to an increased risk for atherosclerosis. To investigate the possible
      adverse effects of periodontitis in maintenance hemodialysis patients, we
      compared periodontal severity with malnutrition and inflammation, which are
      associated with poor atherosclerotic outcome in hemodialysis patients. METHODS:
      Two hundred fifty-three hemodialysis patients were included in this study to
      evaluate clinical periodontal status by using the Plaque Index, Gingival Index,
      and Periodontal Disease Index. Geographic, hematologic, biochemical, and dialysis
      related data also were collected. Values for nutritional and inflammatory
      markers, such as albumin, blood urea nitrogen, creatinine, transferrin, absolute
      lymphocyte count, normalized protein catabolic rate, high-sensitivity C-reactive
      protein, and ferritin, were included for analysis with the Periodontal Index.
      RESULTS: Poor oral health status was shown by 80.6% of hemodialysis patients with
      periodontal disease. In an analysis of geographic and disease-related parameters,
      we found that aging, smoking, diabetes, and longer dialysis duration were
      associated with severity of periodontitis. Parameters of malnutrition and
      inflammation also were associated with poor periodontal status. We next conducted
      multiple regression analysis and found that age, diabetes, smoking, albumin
      level, and dialysis duration were associated independently with periodontitis
      severity in hemodialysis patients. According to the severity of periodontitis,
      there were higher percentiles of patients with malnutrition (chi-square = 13.055;
      P = 0.005) and inflammation (chi-square = 10.046; P = 0.018) in the severe group.
      CONCLUSION: Periodontal health is poor in hemodialysis patients and correlates
      with markers of malnutrition and inflammation. Its diagnosis and treatment
      deserve better awareness.

PMID- 16632021
TI  - Serum troponin T concentration as a predictor of mortality in hemodialysis and
      peritoneal dialysis patients.
AB  - BACKGROUND: Troponin T is a good predictor of all-cause and cardiovascular
      mortality in cardiac patients. Although it is known that troponin T is an
      independent risk factor in dialysis patients as well, its prognostic value when
      measured routinely in clinical practice, particularly in addition to other risk
      indicators, is unclear. METHODS: A cohort of 847 patients who started dialysis
      therapy between 1997 and 2001 and participated in a multicenter follow-up study
      was examined. Clinical data were determined 3 months after the start of dialysis
      therapy. Patients were followed up until date of death or censoring in November
      2003. RESULTS: For patients with troponin T values of 0.05 to 0.10 microg/L,
      hazard ratio for all-cause mortality was 2.2 (95% confidence interval [CI], 1.7
      to 2.8) compared with patients with values less than 0.05 microg/L. For patients
      with values greater than 0.10 microg/L (11%), hazard ratio was 3.3 (95% CI, 2.5
      to 4.5). A survival model with clinical and laboratory risk indicators yielded an
      area under the curve of 0.81, which did not increase when troponin T level was
      added to the model. The area under the curve for troponin T level alone was 0.67.
      No important differences were found between patients on hemodialysis or
      peritoneal dialysis therapy and between patients with high and low residual renal
      function. CONCLUSION: Although troponin T level is an independent risk factor for
      mortality in dialysis patients, it has limited added predictive power as a
      routine screening test over other clinical risk factors in dialysis patients.

PMID- 16632022
TI  - Occurrence of regional left ventricular dysfunction in patients undergoing
      standard and biofeedback dialysis.
AB  - BACKGROUND: Cardiac failure and cardiovascular death are extremely prevalent in
      dialysis patients. Recurrent subclinical myocardial ischemia is important in the
      genesis of heart failure in nondialysis patients. We examined whether this
      phenomenon occurs in response to the stress of hemodialysis (HD). METHODS: Eight
      patients prone to intradialytic hypotension were recruited for a randomized
      crossover study to compare the development of left ventricular regional wall
      motion abnormalities during standard (HD) and biofeedback dialysis. Patients
      underwent serial echocardiography with quantitative analysis to assess ejection
      fraction and regional left ventricular systolic function during both types of
      dialysis. Blood pressure and hemodynamic variables also were measured by using
      continuous pulse wave analysis. RESULTS: Forty-two new regional wall motion
      abnormalities developed in all 8 patients during HD compared with 23 regional
      wall motion abnormalities that developed in 7 patients during biofeedback
      dialysis (odds ratio, 1.8; 95% confidence interval, 1.1 to 3.0). The majority of
      regional wall motion abnormalities showed improvement in function by 30 minutes
      postdialysis. Overall mean regional function was significantly more impaired
      during HD (P = 0.022). At peak stress, ejection fraction (measured by percentage
      of change from baseline) was significantly lower during HD (P = 0.043). Blood
      pressure was higher during biofeedback dialysis, with significantly fewer
      episodes of hypotension (odds ratio, 2.0; 95% confidence interval, 1.01 to 4.4).
      Significantly smaller decreases in stroke volume and cardiac output and a greater
      increment in pulse rate were observed during biofeedback dialysis. CONCLUSION:
      This study shows that reversible left ventricular wall motion abnormalities
      develop during dialysis with ultrafiltration. We also show that this phenomenon
      can be ameliorated by the improved hemodynamic stability of biofeedback dialysis
      and therefore is a potential target for intervention.

PMID- 16632023
TI  - Spinal cord stimulation in hemodialysis patients with critical lower-limb
      ischemia.
AB  - BACKGROUND: Spinal cord stimulation (SCS) has been proposed for the treatment of
      ischemic pain and the prevention or delay of amputation in patients with
      peripheral arterial occlusive disease (PAOD) who are unsuitable for vascular
      reconstruction. PAOD is common in patients with end-stage renal disease and is
      associated with substantial morbidity and mortality. Furthermore, many patients
      are not candidates for limb-sparing procedures and have to undergo primary
      amputation. METHODS: We report our experience with SCS in 8 hemodialysis patients
      with chronic lower-limb ischemia and not suitable for either primary surgical or
      angioplastic intervention or reintervention. Intensity of ischemic pain, quality
      of life, use of analgesic medications, limb survival, and outcome of skin
      ischemic lesions were evaluated before implantation of an SCS device and after 6
      and 12 months of follow-up. RESULTS: No complications from SCS device
      implantation occurred. Both intensity of pain and quality of life significantly
      improved during follow-up. SCS allowed a decrease in pain medication intake in
      all patients. Limb survival at 1 year was 75%. Ischemic skin lesions before
      implantation of an SCS device did not ameliorate during the follow-up period, but
      the appearance of new lesions was not observed. CONCLUSION: Implantation of an
      SCS device in patients with end-stage renal disease with critical limb ischemia
      dramatically improves quality of life and pain relief. In patients assessed at
      Leriche-Fontaine stage 2 or 3, the treatment might delay the appearance of
      ischemic skin lesions and amputation. At these stages, presumed long-term
      benefits could justify the cost of SCS.

PMID- 16632024
TI  - Incidence of atherosclerotic cardiovascular disease among HIV patients receiving
      dialysis.
AB  - BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is increasing in
      incidence in persons with human immunodeficiency virus (HIV). It is not known
      whether the morbidity and mortality rate of ASCVD is similarly increasing among
      patients with HIV end-stage renal disease (ESRD), who are living longer since the
      initiation of newer therapeutic regimens in 1997. METHODS: We conducted a
      population-based study of 8,312 HIV ESRD patients enrolled in the US Renal Data
      System from 1987 to 2001. We determined the incidence of fatal and nonfatal ASCVD
      events stratified by date of dialysis therapy initiation. RESULTS: There were
      3,112 HIV ESRD patients (77.9% men; mean age, 39.6 +/- 9.6 years) who initiated
      dialysis therapy before 1997 and 2,371 patients (71.5% men; mean age, 41.3 +/-
      9.7 years) who initiated dialysis therapy after 1997. Cumulative incidences of
      ASCVD for those initiating dialysis therapy before 1997 compared with after 1997
      were 10.6% versus 13.5% at 12 months, 18.8% versus 27.6% at 24 months, 26.2%
      versus 42.4% at 36 months, and 33.7% versus 65.9% at 48 months (P < 0.0001 by log
      rank). Those who initiated dialysis therapy after 1997 had a greater risk for
      developing ASCVD (adjusted hazard ratio, 1.57; 95% confidence interval, 1.29 to
      1.92) than those who initiated dialysis therapy before 1997 after adjusting for
      demographics and ASCVD risk factors. CONCLUSION: There is an increased risk for
      ASCVD in patients with HIV who initiated dialysis therapy after 1997. This may
      reflect the long-term complications of multidrug regimens, as well as improved
      survival from these regimens leading to prolonged exposure to ASCVD risk factors.

PMID- 16632025
TI  - Pyogenic liver abscess in ESRD patients undergoing maintenance dialysis therapy.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) on dialysis therapy have
      increased susceptibility to bacterial infection. Data regarding pyogenic liver
      abscess in this population are rare. METHODS: We retrospectively examined all
      cases of pyogenic liver abscess in patients undergoing maintenance dialysis
      therapy in 2 tertiary referral centers. Medical records of patients with ESRD
      with a pyogenic liver abscess from January 1995 to September 2004 were studied.
      RESULTS: Twenty-seven of 20,676 admitted patients with ESRD were found to have a
      pyogenic liver abscess. The major predisposing factor was diabetes mellitus
      (59.3%). The most common clinical symptoms were fever and chills (85.2%). A rare
      presentation of hiccup was noted in 2 peritoneal dialysis patients, and
      endophthalmitis was noted in 2 patients with liver abscess caused by Klebsiella
      pneumoniae. Abscesses were located mainly in the right lobe (70.4%) and presented
      as a solitary mass (74.1%). K pneumoniae was the most common bacteria isolated in
      blood cultures (51.9%) and liver abscess aspirates (37%). Invasive drainage
      approaches performed in 17 patients (63%) resulted in a unique complication of
      peritonitis in 4 peritoneal dialysis patients. The difference in mortality rates
      between patients who underwent invasive procedures and those who did not was not
      significant (P = 0.68). The overall in-hospital mortality rate of patients with
      ESRD with a pyogenic liver abscess was 33.3%. CONCLUSION: Although pyogenic liver
      abscess is uncommon in patients with ESRD undergoing maintenance dialysis
      therapy, it is still a disease of significant mortality.

PMID- 16632026
TI  - Effect of diabetes mellitus on muscle size and strength in patients receiving
      dialysis therapy.
AB  - BACKGROUND: Diabetes mellitus (DM) is a potential contributor to the muscle
      abnormalities and poor physical functioning of the dialysis population. METHODS:
      Thirty-three dialysis patients without DM (non-DM group) were compared with 25
      dialysis patients with DM (DM group). Measures were made of cross-sectional area
      and composition of the leg muscles by using proton T1-weighted magnetic resonance
      imaging; body composition by means of dual-energy X-ray absorptiometry; leg
      muscle strength by means of isokinetic knee extension; isometric dorsiflexor
      maximum voluntary contraction by means of force plate; physical activity by means
      of 3-dimensional accelerometry; and functional capacity by using various
      functional tests. RESULTS: The DM group was older, weaker, more atrophic, and had
      a greater amount of intramuscular fat compared with the non-DM group. However,
      when the overall analysis was adjusted for age and sex, there were no differences
      between the 2 groups with respect to muscle cross-sectional area, leg strength,
      or physical activity. To further account for sex and age differences, a paired
      analysis was performed after matching patients by age (within 5 years) and sex (N
      = 16/group). In the matched analysis, only intramuscular fat and leg adipose
      tissue were different between the 2 groups. CONCLUSION: DM is associated with
      more fat within muscles of dialysis patients, but is unrelated to muscle size or
      strength. Demographic differences between the DM and non-DM groups on dialysis
      therapy likely are responsible for the general perception that patients with DM
      are more debilitated.

PMID- 16632027
TI  - Outcomes for adolescent Hispanic hemodialysis patients: findings from the ESRD
      Clinical Performance Measures Project.
AB  - BACKGROUND: There is limited information regarding outcomes of dialytic care for
      Hispanic adolescent hemodialysis patients. METHODS: Ethnicity information was
      collected for all adolescent in-center hemodialysis patients for the Centers for
      Medicare & Medicaid Services 2000 End-Stage Renal Disease (ESRD) Clinical
      Performance Measures Project. Associations between intermediate outcomes and
      Hispanic ethnicity were determined. Associations of ethnicity and other
      demographic/clinical variables with hospitalization and transplantation during
      the 12-month follow-up period were examined. RESULTS: Twenty-two percent of
      patients were identified as Hispanic; 40%, as non-Hispanic black; and 32%, as non
      Hispanic white. Hispanic patients were younger and more likely to have
      congenital/urological causes of ESRD. More Hispanic patients had a mean single
      pool Kt/V of 1.2 or greater compared with non-Hispanic blacks and non-Hispanic
      whites (87% versus 73% and 79%; P = 0.036). More Hispanic patients had a mean
      serum albumin level of 3.5/3.2 g/dL (bromcresol green/bromcresol purple method)
      or greater (> or = 35/32 g/L; 91% versus 82% and 76%; P = 0.017). More Hispanic
      patients compared with non-Hispanic blacks and non-Hispanic whites were dialyzed
      with a catheter for 90 days or longer (30% versus 21% and 23%; P = 0.027). In the
      final multivariate Cox proportional hazard models, Hispanic patients were at a
      slightly decreased risk for hospitalization compared with non-Hispanics (adjusted
      hazard ratio [adjHR], 0.63; P = 0.031) and were as likely to undergo a first
      transplantation as non-Hispanic whites (adjHR, 0.56; P = 0.099). CONCLUSION:
      Adolescent Hispanic hemodialysis patients experience equivalent or better
      intermediate outcomes of dialytic care than non-Hispanics. They experienced a
      decreased risk for subsequent hospitalization and are as likely to undergo
      transplantation within 12 months as non-Hispanic whites.

PMID- 16632028
TI  - Catheter colonization in acute renal failure patients: comparison of central
      venous and dialysis catheters.
AB  - BACKGROUND: Little is known about vascular access infections in patients with
      acute renal failure. METHODS: We prospectively compared infection rates of
      dialysis catheters (DCs) and central venous catheters (CVCs) in patients in the
      intensive care unit treated with renal replacement therapy for acute renal
      failure. The same insertion and maintenance procedures were used for CVCs and
      DCs. To circumvent the allocation bias caused by severity of patient condition,
      only patients with both types of catheters were included. RESULTS: A total of 150
      CVCs and 130 DCs were analyzed in 99 patients with a mean Simplified Acute
      Physiology Score II of 67 +/- 21. The major cause of acute renal failure was
      sepsis (62%). Hospital mortality was 62%. Mean catheter duration was shorter for
      DCs (6.7 +/- 4.4 days) than CVCs (7.8 +/- 4.9 days; P = 0.03). There was no
      difference between CVCs and DCs in cumulative incidence of catheter colonization
      (quantitative catheter cultures > or = 10(3) colony-forming units/mL; 4.7% versus
      6.2%; P = 0.58) or incidence density of catheter colonization per 1,000 catheter
      days (5.9 versus 9.1; P = 0.44, respectively). There also was no difference
      between CVCs and DCs in cumulative incidence and incidence density regardless of
      whether catheters were placed at the internal jugular (P = 0.34 and P = 0.23) or
      femoral site (P = 0.57 and P = 0.80), respectively. Three cases of CVC-related
      bacteremia (the same microorganism responsible for both catheter colonization and
      blood culture result) were recorded, but none with DC use. CONCLUSION: When
      severity of patient condition is controlled for, epidemiological characteristics
      of colonization in CVCs and DCs are similar if similar infection control measures
      are used for insertion and maintenance.

PMID- 16632029
TI  - Carotid plaques and their predictive value for cardiovascular disease and all
      cause mortality in hemodialysis patients considering renal transplantation: a
      decade follow-up.
AB  - BACKGROUND: Carotid plaque formation is very common in dialysis patients. The
      prognostic value of plaques, both calcified and noncalcified, rarely was
      investigated prospectively in these patients. By using a carotid plaque score,
      this study aims to determine the risk for combined cardiovascular disease (CVD)
      events and all-cause mortality in 165 hemodialysis patients in a long-term follow
      up considering phases of renal transplantation. METHODS: Baseline carotid
      ultrasonography was performed in 165 hemodialysis patients to screen for carotid
      plaques. Patients subsequently were followed up for a period up to 13 years
      (average, 86 months). Because of biases associated with renal transplantation, 3
      methods of multivariate analysis were compared by using Cox proportional hazards
      regression models. RESULTS: Plaques were present in 107 of 165 patients (65%).
      During the observation period, 50 patients (30%) experienced a combined CVD
      event, 95 patients (58%) died, and 79 patients (48%) underwent at least 1 renal
      transplantation. Mean plaque score differed significantly between patients who
      reached an end point and those who did not (CVD events, 3.1 +/- 2.7 versus 2.0 +/
      2.4; P = 0.01; all-cause mortality, 3.5 +/- 2.6 versus 0.9 +/- 1.3; P < 0.001).
      Plaque score entered all 3 tested Cox regression models for CVD events and all
      cause mortality. The lowest statistical power was associated with censoring at
      the time of renal transplantation. Not considering transplantation at all
      neglected a major change in risk. CONCLUSION: We identified carotid plaque score
      and treatment modality as highly significant predictors for CVD events and all
      cause mortality.

PMID- 16632030
TI  - Urinary beta2-microglobulin is associated with acute renal allograft rejection.
AB  - BACKGROUND: Identifying urinary biomarkers associated with acute rejection (AR)
      of kidney allografts could improve recipient care by allowing AR to be diagnosed
      noninvasively and treated earlier. We attempted to identify novel biomarkers
      associated with AR by analyzing urinary proteins by using matrix-associated laser
      desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). METHODS:
      Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients
      with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples
      from 29 kidney donors, and 10 subjects with proteinuric native kidney disease.
      RESULTS: In samples obtained at the time of AR, we identified a protein peak at
      11.7 kd that correlated strongly with AR. In regard to its predictive power for
      AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive
      predictive value of 89%, and negative predictive value of 70.6%, suggesting that
      this protein is highly associated with AR. We identified this peak as being beta2
      microglobulin. This was validated by using enzyme-linked immunosorbent assay,
      which documented the presence of high urinary beta2-microglobulin levels in
      subjects with AR. CONCLUSION: Beta2-microglobulin could be a strong biomarker for
      AR if used in conjunction with other biomarkers, producing an AR-specific urinary
      protein signature. This possibility must be confirmed in a larger cohort of
      kidney transplant recipients.

PMID- 16632031
TI  - Pseudomyxoma peritonei as a cause of culture-negative peritonitis for a patient
      undergoing peritoneal dialysis.
AB  - Culture-negative peritonitis accounts for up to 20% of all peritoneal dialysis
      related peritonitis, the causes of which include culture-associated technical
      errors, prior use of antibiotics, infection caused by certain unusual or
      fastidious microorganisms, the development of abdominal or retroperitoneal organ
      inflammation, and the presence of malignancies. Here, we report a patient with
      end-stage renal disease receiving peritoneal dialysis who presented with culture
      negative peritonitis and ultrafiltration failure caused by the rare pseudomyxoma
      peritonei. For cases of culture-negative peritonitis such as this, early imaging
      studies may help recognize intraperitoneal/retroperitoneal visceral inflammation
      and malignant conditions.

PMID- 16632032
TI  - AH amyloidosis associated with lymphoplasmacytic lymphoma secreting a monoclonal
      gamma heavy chain carrying an unusual truncated D segment.
AB  - To date, the presence of amyloidosis associated with immunoglobulin heavy chain
      (AH amyloidosis) was reported in only 7 cases. Although AH amyloidosis is caused
      mainly by plasma cell dyscrasia, as in AL amyloidosis, we report a 61-year-old
      patient who presented with nephrotic syndrome caused by AH amyloidosis associated
      with lymphoplasmacytic lymphoma. Biochemical and molecular analyses of the
      deposited amyloid fibrils and heavy-chain genes of lymphocytes showed that
      proliferative lymphoma cells produced a gamma heavy chain, not a mu heavy chain,
      which carried an unusual truncated diversity (D) segment of the variable region.
      Our results indicate that production of the abnormal heavy chain caused by the
      partially deleted D segment gene is responsible for gamma heavy-chain-related
      amyloid fibril formation in this patient.

PMID- 16632033
TI  - Fatal relapse of ANCA-associated glomerulonephritis triggered by successive
      Epstein-Barr and varicella zoster virus infections.

PMID- 16632035
TI  - Should we reconsider the advanced glycation end product issue in hemodialysis
      patients?

PMID- 16632036
TI  - Multiple mechanisms for abnormal selenium levels and vascular disease in renal
      failure.

PMID- 16632038
TI  - The kinetics of proinflammatory cytokines in murine peritoneal macrophages
      infected with envelope protein-glycosylated or non-glycosylated West Nile virus.
AB  - The envelope (E) protein glycosylation status of the New York strain of West Nile
      (WN) virus is an important determinant of virus neuroinvasiveness. To elucidate
      the determinant of the difference between E protein-glycosylated and non
      glycosylated WN virus infections, the cytokine expression of murine peritoneal
      macrophages infected with each virus was examined. Tumor necrosis factor (TNF)
      alpha and interleukin (IL)-1beta were up-regulated with replication of the E
      protein-glycosylated virus. Interferon (IFN) beta and IL-6 were up-regulated with
      the clearance of both viruses. These results suggest that TNFalpha and IL-1beta
      expression are related to the virulence of E protein-glycosylated WN virus.

PMID- 16632039
TI  - Exogenous nitric oxide inhibits Crimean Congo hemorrhagic fever virus.
AB  - Crimean Congo hemorrhagic fever virus (CCHFV) is a geographically widespread
      pathogen that causes severe hemorrhagic fever with high mortality. Even though
      one of the main objectives focuses on the progress of antiviral agents, the
      research on CCHFV is strongly hampered due to its BSL-4 classification. Nitric
      oxide (NO), a mediator with broad biological effects, has been shown to possess
      inhibitory properties against various pathogens. The molecule constitutes a
      component of the innate immunity and serves to assist in the early immunological
      events where it contributes to clearance of microorganisms. In this study, we
      investigated the inhibitory properties of exogenous NO on CCHFV. We found that NO
      had a significant antiviral activity against CCHFV replication. By using the NO
      donor S-nitroso-N-acetylpenicillamine (SNAP) we were able to show up to 99%
      reduction in virion progeny yield. In contrast, 3-morpholinosydnonimine
      hydrochloride (SIN-1), a peroxynitrite donor, had no significant antiviral
      activity against CCHFV. Furthermore the expression of viral proteins; the
      nucleocapsid protein and the glycoprotein, were clearly reduced with increasing
      concentrations of SNAP. We have also shown that the amount of total vRNA in SNAP
      treated cells was reduced by about 50% compared to the controls.

PMID- 16632040
TI  - The effects of albumin-coated microbubbles in DNA delivery mediated by
      therapeutic ultrasound.
AB  - The application of therapeutic ultrasound (TUS) in combination with contrast
      agents (USCA) to mediate gene delivery relies on the understanding of the
      bioeffects involved. The objective of this study was to evaluate the various
      bioeffects generated by albumin-coated microbubbles: Optison, an USCA, when
      applied with TUS operated for 10-30 min, on cells and on DNA transfection. This
      study reveals that Optison microbubbles were still acoustically active after long
      term TUS application of 30 min. Optison enhances TUS-gene transfection by
      increasing the number of plasmids in the cells and also by distributing the
      plasmids to more cells, without significant decrease in cell viability. Optison
      also interacts with the DNA to further enhance transfection in a mechanism not
      necessarily involving cavitation. However, Optison affects mainly the cell
      cytoplasmatic membrane, without interfering with DNA intracellular trafficking.
      Using high-resolution scanning electron microscopy (HRSEM), the bioeffects on
      cell membrane induced by TUS-Optison were observed, demonstrating that Optison
      lead to a rougher surface, characterized by depressions that are reversible
      within 24-h post TUS. These effects are different from those observed when only
      TUS was applied. The findings from this study suggest that albumin-coated
      microbubbles enhances transfection when using TUS for 10-30 min, and that
      microbubbles play a major role in elevating cell transfection level and
      efficiency.

PMID- 16632042
TI  - Sonographic differentiation of digital tendon rupture from adhesive scarring
      after primary surgical repair.
AB  - PURPOSE: After the surgical repair of finger tendons finger range of motion may
      be limited by tendon rupture or adhesive scarring. Differentiating tendon rupture
      from adhesive scarring may be difficult clinically. Digital tendon sonography
      allows the evaluation of tendon integrity in a dynamic setting. Our objective was
      to determine if sonography could differentiate tendon rupture from adhesive
      scarring in patients who have had primary tendon repair. METHODS: A retrospective
      review was performed of the radiographic, clinical, and surgical records of
      patients referred for finger sonography over a 2-year period. Twenty-eight digits
      in 21 patients were evaluated for finger tendon disruption after primary surgical
      repair. The diagnosis of complete tendon rupture was made when 1 or more of the
      following was identified: a gap separating the proximal and distal tendon
      margins, visualization of only the proximal tendon margin, or visualization of
      only the distal tendon margin. Adhesive scarring was diagnosed if the tendon
      appeared intact with abnormal peritendinous soft tissue abutting or partially
      encasing the tendon, with synovial sheath thickening, or with restricted tendon
      motion during dynamic evaluation. RESULTS: Sonography correctly identified tendon
      rupture or adhesive scarring in 27 of 28 digits with 1 false-positive case
      (sensitivity, 100%; specificity, 93%; positive-predictive value, 93%; negative
      predictive value, 100%; accuracy, 96%). CONCLUSIONS: Sonography is an accurate
      modality for differentiating tendon rupture from adhesive scarring in patients
      with prior surgical tendon repair. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic,
      Level I.

PMID- 16632043
TI  - Effects of monofilament nylon coated with basic fibroblast growth factor on
      endogenous intrasynovial flexor tendon healing.
AB  - PURPOSE: We developed a monofilament nylon thread that can release various growth
      factors to enhance intrinsic reparative processes after flexor tendon injury. We
      evaluated the properties of this thread in vitro and in vivo. METHODS: Nylon
      threads were coated with gelatin that subsequently was cross-linked in
      glutaraldehyde. The thread was soaked in basic fibroblast growth factor (bFGF)
      solution (400 microg/mL). Exogenous bFGF in the thread was released constantly
      over the course of 1 week. The biologic activity of bFGF and the biomechanical
      strength of the thread were examined in vitro and its efficacy was investigated
      in an in vivo rabbit tendon repair model after early flexion exercises. The
      sutured sites were examined histologically (hematoxylin-eosin,
      immunohistochemistry, in situ hybridization), biochemically (Western blot test),
      and biomechanically (ultimate load) after surgery. RESULTS: This gelatin-coated
      thread absorbed iodine 125-labeled bFGF in a time-dependent manner. The total
      amount of bFGF absorbed by the thread within the tendon tissue was between 3 and
      15 mug depending on the concentration of bFGF solution. Basic fibroblast growth
      factor protein was delivered selectively-not in the surrounding scar but in the
      repaired tendon-for 3 weeks. Histologic analysis showed that the cellular density
      at the repaired site increased in accordance with the expression of bFGF
      messenger RNA and protein in the tendon. Endogenous bFGF expression seemed to be
      enhanced transiently by exogenous bFGF during the first few weeks. The epitenon
      showed a vigorous fibroblastic response to the coated thread and the ultimate
      load also was increased significantly at 3 weeks after surgery. CONCLUSIONS: This
      bFGF-coated nylon suture gave excellent results in delivering a drug selectively
      to tendon; it also induced an increase of biomechanical strength and a thickening
      of the epitenon layer in vivo during a 3-week period, thereby accelerating
      cellular proliferation, initially peripherally and later centrally. This system
      may become a therapeutic tool to be used in hand surgery.

PMID- 16632044
TI  - Incidence and development of trigger thumb in children.
AB  - PURPOSE: Whether trigger thumb is congenital or acquired remains controversial.
      The purpose of this study was to identify whether trigger thumb is present at
      birth and to clarify whether trigger thumb represents a developmental condition.
      METHODS: We examined 1,116 babies born at Yamagata Prefectural Nihonkai Hospital
      within 14 days after birth. All patients were examined by the author (N.K.), a
      hand surgeon. Patients were followed up to determine whether trigger thumb would
      present later even though it was not present at birth. We informed parents about
      the development of trigger thumb by providing informational sheets for neonatal
      screenings after hospital discharge. They were asked to check their child for a
      year or more to see if any flexion deformity of the interphalangeal joint of the
      thumb occurred. After discharge from the hospital, the family was responsible for
      noticing trigger thumb in their infant and seeking medical treatment. RESULTS:
      Trigger thumb was not identified in any patient at birth. Responses were obtained
      from 601 families. Trigger thumb manifested in 2 thumbs of 2 children in the
      screening group at 8 and 11 months after birth; however, 3 additional children
      developed trigger thumb at 15, 21, and 30 months of age. CONCLUSIONS: The
      incidence of acquired trigger thumb in children 1 year of age was 3.3 per 1,000
      live births. It is unlikely that this study identified all cases of trigger thumb
      in patients older than 1 year in the primary screening group. The results of this
      follow-up study, however, suggest that trigger thumb is not present at birth but
      develops with postnatal growth.

PMID- 16632045
TI  - Abnormal triangular epiphysis causing angular deformity of the thumb.
AB  - PURPOSE: To present a triangular-shaped abnormal secondary ossification center of
      the distal phalanx causing angular deformity of the thumb and the surgical
      outcome of corrective closing-wedge osteotomy for this deformity. METHODS: We
      treated 6 patients with abnormal triangular epiphysis in the distal phalanx of
      the thumb, including 3 bilateral cases. The average age was 43 months and there
      were 2 boys and 4 girls. Of the 9 thumbs intraepiphyseal closing-wedge osteotomy
      was performed in 5 and proximal phalangeal closing-wedge osteotomy was performed
      in 4. We measured the deformities in degrees of angulation and the range of
      motion of the interphalangeal (IP) joint. The average duration of the follow-up
      period was 27 months after the surgery. RESULTS: Preoperative angular deformity
      of ulnar deviation averaged 30 degrees , which was reduced to an average of 12
      degrees after osteotomy at the last follow-up assessment. All osteotomies healed
      and there was no evidence of physeal or articular damage. Interphalangeal joint
      range of motion did not decrease after surgery in all cases. Patients and parents
      were satisfied with the results of the surgery, although mild deformity persisted
      in the interphalangeal joint when in the flexed position after proximal
      phalangeal osteotomy. CONCLUSIONS: Abnormal triangular epiphysis causing angled
      thumb is different from delta bone and can be treated with either intraepiphyseal
      or proximal phalangeal closing-wedge osteotomy. The intraepiphyseal procedure,
      however, could achieve better deformity correction regardless of the
      interphalangeal joint position. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic,
      Level IV.

PMID- 16632046
TI  - Ulnar tendinous interconnection in type IIIA thumb hypoplasia--a pollex adductus.
AB  - We present an anatomic variation of type IIIA thumb hypoplasia in which a
      tendinous interconnection between the flexor pollicis longus and the extensor
      pollicis longus occurred on the ulnar aspect of the thumb. Interconnection
      between extrinsic flexor and extensor systems is well known in type IIIA thumb
      hypoplasia and has been reported on the radial side (pollex abductus). In our
      patient the ulnar location of the interconnection remained unrecognized until
      recurrence of the deformity in adolescence.

PMID- 16632047
TI  - Intraoperative measurement of pressure adjacent to the ulnar nerve in patients
      with cubital tunnel syndrome.
AB  - PURPOSE: Little is known about whether the pressure adjacent to the ulnar nerve
      actually is increased in patients with cubital tunnel syndrome or if it is a
      causative factor. We measured the pressure adjacent to the ulnar nerve in
      patients with cubital tunnel syndrome during surgery and verified whether or not
      there was an association with patient age, duration of the disease, motor nerve
      conduction velocity, and severity of the ulnar nerve neuropathy. METHODS: Eight
      elbows in 8 patients with an average age of 62 years were treated surgically and
      the extraneural pressures within the cubital tunnel were measured during surgery
      by using a fiberoptic microtransducer. Pressure was measured 3 times with the
      elbow fully extended and then 3 times with the elbow flexed 130 degrees. The
      transducers were placed at 1, 2, and 3 cm distal to the proximal edge of the
      Osborne ligament. The severity of the neuropathy was evaluated according to
      Akahori's classification. The ulnar nerve palsy was graded as stage III in 5
      patients and as stage IV in 3 patients. RESULTS: The average pressures within the
      cubital tunnel at 1, 2, and 3 cm distal to the proximal edge of the cubital
      tunnel retinaculum with the elbow flexed were 105, 29, and 18 mm Hg,
      respectively. The pressures at 1 and 2 cm distal to the proximal edge of the
      cubital tunnel retinaculum were significantly higher in elbow flexion than in
      elbow extension. There was also a positive correlation between the pressure and
      patient age but this was not significant The pressures correlated significantly
      with the stage of ulnar nerve neuropathy, motor nerve conduction velocity, and
      disease duration. CONCLUSIONS: The extraneural pressure within the cubital tunnel
      actually was increased in the patients and compression of the ulnar nerve might
      be a causative factor of cubital tunnel syndrome.

PMID- 16632048
TI  - Long-term follow-up evaluation of denervation of the wrist.
AB  - PURPOSE: To evaluate the indications and results of complete wrist denervation
      and to focus on the correlation between results and length of follow-up
      evaluation. METHODS: A retrospective review was performed of 71 complete
      denervations of the wrist joint in 70 patients with an average follow-up period
      of 9.6 years (range, 1-23 y) using the Disabilities of the Arm, Shoulder, and
      Hand (DASH) questionnaire. The denervations were performed according to the
      description by Wilhelm. All patients were asked to provide a DASH score. The
      indications for surgery were degenerative changes caused by scaphoid nonunions
      (25), distal radius fracture (11), Kienbock's disease (11), primary degenerative
      arthritis (9), scapholunate dissociation (8), and others (7). RESULTS: The
      average DASH score was 26 (range, 0-88). Thirty-nine patients (40 wrists)
      reported considerable improvement, 8 reported little improvement, and 10 reported
      temporary improvement after surgery. Seven experienced no change and 6
      experienced worsening after surgery. Twenty-two patients were completely free of
      pain and 13 (14 wrists) had little, 20 had moderate, 11 had considerable, and 4
      had severe pain. Forty-eight patients (49 wrists) stated that they would repeat
      the denervation and 61 (62 wrists) were able to keep their former occupations.
      There was a trend toward lower (improved) DASH scores in patients with longer
      follow-up periods but this did not reach statistical significance. The best
      results were achieved in patients with scapholunate dissociations and the worst
      results occurred in old distal radius fractures. Patient age did not influence
      the results. Nine patients with unsatisfactory results needed a second procedure.
      CONCLUSIONS: Complete wrist denervation resulted in subjective long-term
      improvement in two thirds and in a complete or marked pain relief in half of the
      patients. Patients with longer postoperative time and younger age did not affect
      the results adversely. This procedure is simple and fast, does not decrease range
      of motion, and leaves all other surgical options open. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic, Level IV.

PMID- 16632049
TI  - The cutaneous innervation of the dorsal hand: detailed anatomy with clinical
      implications.
AB  - PURPOSE: Detailed knowledge of the anatomy of the cutaneous innervation to the
      dorsal surface of the hand is valuable information. Because surgical access to
      the wrist often is obtained via the dorsal skin it would be helpful particularly
      to delineate an area where surgical incisions would not injure underlying nerves.
      METHODS: Thirty cadaver forearms were dissected carefully to examine in detail
      the anatomy of the lateral antebrachial cutaneous nerve, the superficial branch
      of the radial nerve, and the dorsal branch of the ulnar nerve. Each hand then was
      evaluated for an area free of any major nerve branches over the dorsal wrist.
      RESULTS: Although the innervation to the dorsal hand varies certain patterns
      exist. The innervation pattern between the superficial branch of the radial nerve
      and the dorsal branch of the ulnar nerve is distributed evenly, dual innervation
      is frequent between the 2 nerves, and the lateral antebrachial cutaneous nerve is
      a common contributor to the innervation of the thumb. The superficial branch of
      the radial nerve and the dorsal branch of the ulnar nerve have identifiable
      branching patterns and have been classified according to a system developed for
      this study. CONCLUSIONS: Two classification systems based on detailed dorsal hand
      cutaneous innervation patterns can be used to specify the placement of a safe
      dorsal skin incision away from major nerve branches.

PMID- 16632050
TI  - Mycobacterium tuberculosis-induced carpal tunnel syndrome: management and follow
      up evaluation.
AB  - PURPOSE: To determine the clinical characteristics of 12 patients with
      Mycobacterium tuberculosis-induced carpal tunnel syndrome. This article also
      presents our intraoperative findings and surgical treatment results. METHODS:
      Twelve patients with tuberculosis-induced carpal tunnel syndrome who had surgery
      during a 10-year period that began in March 1991 were reviewed. The entrance
      criterion was a positive histologic report of tuberculosis for surgical
      specimens. The preoperative evaluation leading to diagnosis was reviewed for all
      patients. Transection of the transverse carpal ligament and complete synovectomy
      were performed for all patients. After surgery the patients were given an
      antituberculosis regimen for 1 year and were followed up for an average of 6
      years. RESULTS: Twelve cases from a total of 1,180 patients with carpal tunnel
      syndrome were traced to M tuberculosis involvement of synovial tissue of the
      flexor tendons. Ten patients had large rice bodies in thick synovial membranes,
      and in the other 2 patients thick synovial tissue with yellow exudates were
      observed during surgery. In contrast to tendon involvement with rupture, no
      direct median nerve involvement was noted. Histopathologic study results of
      surgical specimens were positive for tuberculosis in all patients. Eight of 10
      initial smears showed acid-fast bacillus and all 10 cultures of the specimens
      were positive for tubercle bacilli. Surgery and antituberculosis therapy were
      associated with a desirable outcome and sensory disturbance in the median nerve
      distribution resolved in all patients. Anterior wrist swelling disappeared and
      there has been no clinical or laboratory evidence of recurrence in all treated
      patients. CONCLUSIONS: Early diagnosis and surgical treatment combined with
      antituberculosis medical treatment are important in treating this condition. All
      patients treated were relieved of symptoms of synovial proliferation at the
      wrist, with no recurrence of the condition during the follow-up period. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 16632051
TI  - A capsular-based vascularized distal radius graft for proximal pole scaphoid
      pseudarthrosis.
AB  - PURPOSE: To evaluate the clinical results of the application of a capsular-based
      dorsal distal radius vascularized bone graft in scaphoid proximal pole nonunions.
      METHODS: Thirteen patients with symptomatic nonunion at the proximal pole of the
      scaphoid (10 with avascular necrosis) were treated and reviewed retrospectively.
      The vascularized bone graft was harvested from the distal aspect of the dorsal
      radius and was attached to a wide distally based strip of the dorsal wrist
      capsule. It was inserted press-fit into a dorsal trough across the nonunion site
      after scaphoid fixation with a Herbert screw. RESULTS: After a mean follow-up
      period of 19 months 10 of the 13 nonunions (8 of the 10 with avascular necrosis)
      achieved solid bone union. No complications other than the 3 persistent nonunions
      occurred. CONCLUSIONS: Results of the use of a capsular-based vascularized bone
      graft from the distal radius for proximal pole scaphoid nonunions compare
      favorably with the results of pedicled or free vascularized grafts. It is a
      simple technique that eliminates the need for dissection of small-caliber pedicle
      or microsurgical anastomoses. No donor site morbidity was observed. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 16632052
TI  - Resection of the scaphoid distal pole for symptomatic scaphoid nonunion after
      failed previous surgical treatment.
AB  - PURPOSE: To evaluate the results of resection of the scaphoid distal pole for
      symptomatic scaphoid nonunion after failed prior surgical treatment. METHODS:
      Thirteen patients who were treated with resection of the scaphoid distal pole for
      persistent nonunion after previous surgical treatment were included in this
      study. The mean follow-up period was 5 years. Evaluation included measurement of
      wrist range of motion, assessment of pain, and evaluation of radiographic
      parameters. The Disabilities of the Arm, Shoulder, and Hand score was used to
      determine the functional outcome after the excision. RESULTS: Before surgery all
      but 1 patient reported pain. After surgery 2 patients presented with mild pain
      during strenuous activity. Mean wrist flexion and extension increased
      significantly, by 23 degrees and 29 degrees, respectively. The postoperative
      Disabilities of the Arm, Shoulder, and Hand score was 25 +/- 19 points. There was
      a significant increase in the radiolunate angle, indicating dorsal intercalated
      segment instability deformity in 6 patients. CONCLUSIONS: Scaphoid distal pole
      excision remains a valuable treatment option for patients for whom multiple
      attempts at union have failed previously and who have no associated complete
      scapholunate ligament tears. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level
      IV.

PMID- 16632053
TI  - The hysteresis effect in carpal kinematics.
AB  - PURPOSE: Carpal bones show hysteresis that is dependent on the direction of wrist
      motion during a continuous active loading protocol. We describe an accurate
      methodology for analyzing the hysteresis effect and we apply this model to
      analyze the effect of sequential ligament sectioning on scapholunate instability.
      METHODS: In 8 fresh cadaver forearms scaphoid, lunate, and third metacarpal
      motions were recorded while each wrist was moved in continuous cycles of active
      motion in flexion-extension and radioulnar deviation. Motions were analyzed for
      the intact state and after sequential sectioning of the scapholunate
      interosseous, scaphotrapezium, and radioscaphocapitate ligaments. Carpal motion
      was curve-fitted with respect to the third metacarpal motion using optimization
      criteria. The area between the 2 curves that represents opposite directions of
      wrist motion was measured to give the total hysteresis area. Repeated-measures
      analysis of variance was used to determine significance. RESULTS: In the flexion
      extension trials the scaphoid and lunate total hysteresis area was significantly
      greater than the intact state only after all 3 ligaments were sectioned. In the
      radioulnar deviation trials the scaphoid total hysteresis area was significantly
      greater than the intact after just scapholunate interosseous ligament sectioning;
      however, the lunate total hysteresis area decreased with additional sequential
      sectionings in 4 of the 8 specimens as compared with the intact state. These 4
      specimens started with a significantly greater intact total hysteresis area than
      the other 4 specimens. CONCLUSIONS: The computation of the total hysteresis area
      from the hysteresis effect was found to be a sensitive technique to determine the
      subtle onset of abnormal carpal motion. By using this technique in a ligament
      sectioning study significant increases in the total hysteresis area were seen
      after just scapholunate interosseous ligament sectioning during wrist radioulnar
      deviation. This subtle change may signify the onset of dynamic scapholunate
      instability. The total hysteresis area of the lunate in a subset of lax specimens
      did not increase after ligament sectioning. This divergent behavior may explain
      why some patients with scapholunate instability do not develop dorsal
      intercalated segmental instability.

PMID- 16632054
TI  - An anatomic study of the triquetrum-hamate joint.
AB  - PURPOSE: To investigate the articulating surface of the triquetrum-hamate joint
      (TqH). METHODS: The carpal bones of 46 wrist specimens were examined. The shape
      of the TqH joint surfaces were investigated, with focus on variations in the
      shape of the hamate and corresponding triquetrum and the presence and position of
      convex and concave surfaces. RESULTS: Two distinct patterns of hamate TqH
      articular surfaces were identified, designated type I (31 of 46) and type II (15
      of 46). The triquetral TqH articular surface also was found to have 2 distinct
      patterns, designated type A (18 of 46) and type B (15 of 46). Of the triquetrums
      examined 13 of 46 had characteristics that were a variable mixture of the 2
      identifiable triquetral surface types, but these did not have sufficient
      similarity to constitute a third triquetrum surface type. The corresponding
      articulation patterns of these joint surfaces showed a strong trend for a type A
      triquetrum to articulate with a type I hamate (18 of 46 of all joints) and for a
      type B triquetrum to articulate with a type II hamate (13 of 46 of all joints).
      No association was seen between lunate types and type I or type II hamates.
      CONCLUSIONS: These findings suggest the existence of 2 distinct TqH joint
      patterns, which have been termed TqH-1 and TqH-2. There appears to be a spectrum
      of variation between these 2 identifiable types. As a result, the TqH is best
      described as a spectrum, with TqH-1 at one end and TqH-2 at the other. A TqH-1
      joint is a helicoidal configuration. It is double-faceted, with the hamate and
      the triquetrum articular surfaces possessing complementary concave and convex
      parts. A TqH-2 joint has a predominantly oval convex shape, whereas the primarily
      concave triquetrum is better described as a dish for the flatter hamate. It has
      no hamate groove or distal ridge.

PMID- 16632055
TI  - Transscaphoid transcapitate transtriquetral perilunate fracture-dislocation: a
      case report.
AB  - We present a rare stage III greater arc fracture-dislocation of the carpus
      including transscaphoid, transcapitate, and transtriquetral dorsal perilunate
      fracture-dislocation.

PMID- 16632056
TI  - Pisotriquetral arthrodesis as an alternative to excision for pisotriquetral
      instability in high-demand patients: a case report in a gymnast.
AB  - A gymanast developed ulnar wrist pain caused by pisotriquetral instability.
      Pisotriquetral arthrodesis resulted in pain relief and sufficient functional
      return to allow her to return to gymnastics. Pisotriquetral arthrodesis is a
      feasible alternative to pisiform excision worth consideration in high-demand
      patients with symptomatic pisotriquetral instability or arthrosis. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic, Level V.

PMID- 16632057
TI  - Volar fixed-angle plating of distal radius extension fractures: influence of
      plate position on secondary loss of reduction--a biomechanic study in a cadaveric
      model.
AB  - PURPOSE: Treatment of extension fractures of the distal radius with volar fixed
      angle plates has become increasingly popular in the past 2 years. It has been
      observed clinically that placement of the distal screws as close as possible to
      the subchondral zone is crucial to maintain radial length after surgery. The
      purposes of this study were (1) to evaluate radial shortening after plating with
      regard to plate position and (2) to evaluate whether plate position has an
      influence on the strength and rigidity of the plate-screw construct. METHODS: An
      extra-articular fracture (AO classification, A3) was created in 7 pairs of fresh
      frozen human cadaver radiuses. The radiuses then were plated with a volar distal
      radius locking compression plate. Seven plates were applied subchondrally; 7
      plates were applied 4.5 mm to 7.5 mm proximal to the subchondral zone. The
      specimens were loaded with 800-N loads for 2,000 cycles to evaluate radial
      shortening in the 2 groups. Each specimen then was loaded to failure. RESULTS:
      Radial shortening was significantly greater when the distal screws were placed
      proximal to the subchondral zone. The amount of shortening after cyclic loading
      correlated significantly with the distance the distal screws were placed from the
      subchondral zone. Rigidity of the plate systems was significantly higher in
      radiuses in which the distal screws were placed close to the subchondral zone.
      CONCLUSIONS: To maintain radial length after volar fixed-angle plating, placement
      of the distal screws as subchondral as possible is essential. The subchondral
      plate-screw-bone constructs showed significantly greater rigidity, indicating
      higher resistance to postoperative loads and displacement forces.

PMID- 16632058
TI  - The use of tricorticocancellous bone graft in severely comminuted intra-articular
      fractures of the distal radius.
AB  - PURPOSE: We report the results of a retrospective study of the use of
      tricorticocancellous iliac crest bone graft in 12 patients with acute AO type
      C3.2 or type C3.3 fractures of the distal radius who were followed up for at
      least 1 year. METHODS: Twelve of 17 patients treated with the protocol were
      available for follow-up evaluation. All fractures were treated with open
      reduction and combined internal and external fixation. Five fractures were plated
      dorsally, 1 volarly, and 5 volarly and dorsally. RESULTS: Five patients had AO
      type C3.2 fractures and 7 had AO type C3.3 fractures. Nine of 10 radiographic
      parameters that were restored to near-normal values during the surgery were
      maintained at near-normal levels at the final follow-up evaluation at a mean of
      28 months after surgery. Nine fractures had less than 2 mm of articular step-off
      of the distal radius and 8 had less than 3 mm of total articular incongruity (gap
      plus step-off). In 10 patients the radial length was restored to at least 10 mm.
      The mean arc of flexion-extension was 67% and the mean grip strength was 57% of
      that of the uninjured side. According to the Gartland and Werley demerit-point
      system 5 of the patients had good or excellent results. According to the modified
      Green and O'Brien clinical rating system 2 patients had good or excellent
      results. Poor results for 2 patients according to the demerit-point system and
      for 6 patients according to the Green and O'Brien clinical rating system were
      associated with severe ipsilateral soft-tissue and osseous injuries of the wrist,
      forearm, and arm. The total articular incongruity had a moderately strong
      correlation with the outcome as assessed by the demerit-point system.
      CONCLUSIONS: Tricorticocancellous bone grafting in conjunction with combined
      internal and external fixation is a satisfactory treatment that can lead to a
      high rate of return to work and sports, a high level of patient satisfaction, and
      a low rate of complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level
      IV.

PMID- 16632059
TI  - Fifteen-year outcome of displaced intra-articular fractures of the distal radius.
AB  - PURPOSE: We previously reported the functional and radiographic outcomes of 21
      young adults at an average of 7 years after open reduction and internal fixation
      of an intra-articular distal radius fracture (original study). The purpose of the
      current investigation was to evaluate the same cohort at an average of 15 years
      after surgery to evaluate the effect of additional time on both function and
      radiographic appearance. METHODS: We re-evaluated 16 of the original patients at
      an average of 15 years after surgery. Subjective assessment was performed with
      the Musculoskeletal Functional Assessment and the Hand Function Sort
      questionnaires. Objective assessment included a detailed physical examination and
      strength measurement. Standardized radiographs and computed tomography were used
      to assess wrist morphology, residual articular step and gap displacement, and the
      presence and degree of arthrosis. RESULTS: Subjectively patients continued to
      function at a high level at the last follow-up evaluation: the average
      Musculoskeletal Functional Assessment score was 10 and 14 of the 16 patients
      functioned at a high level according to the Hand Function Sort. Strength and
      range of motion remained essentially unchanged from the original report.
      Radiocarpal arthrosis was noted in 13 of the 16 wrists and joint space was
      reduced an additional 67% compared with the 7-year follow-up evaluation.
      Nonetheless there continued to be no correlation between the presence or degree
      of arthrosis and upper-extremity function. CONCLUSIONS: Radiocarpal arthrosis
      after intra-articular distal radius fractures can be expected to worsen over
      time. Despite joint space narrowing and evidence of advanced arthrosis, however,
      patients maintained a high level of function at the long-term follow-up
      evaluation. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic, Level II.

PMID- 16632060
TI  - First web-space reconstruction by the anterolateral thigh flap.
AB  - Four patients with severe contracture of the first web space were treated with an
      anterolateral thigh perforator flap. The flap size ranged from 10 to 13 cm in
      length and from 7 to 8 cm in width. The donor site was closed directly and
      thinning of the flap was performed in all cases. All flaps survived and there
      were no re-explorations. Web space opening was maintained over the follow-up
      period. There was an average postoperative increase of the angle of the first web
      space of 61 degrees. The thinned anterolateral thigh flap provides a pliable
      vascularized tissue for resurfacing the skin after release of severe contracture
      of the first web space and represents a reliable alternative to other flaps.

PMID- 16632061
TI  - Injuries to the finger flexor pulley system in rock climbers: current concepts.
AB  - Closed traumatic ruptures of finger flexor tendon pulleys began to be recognized
      specifically over the past several decades. This injury, although rare in the
      general population, is seen more commonly in rock climbers. This article analyzes
      this type of injury and the current diagnostic and therapeutic criteria.
      Ultrasound and magnetic resonance imaging are used to differentiate between a
      pulley strain, partial rupture, complete rupture, or multiple ruptures. Grade I
      to III injuries (strains, partial rupture, single ruptures) are treated
      conservatively with initial immobilization and early functional therapy under
      pulley protection. Grade IV injuries (multiple ruptures) require surgical repair.

PMID- 16632062
TI  - Radial nerve injuries associated with humeral fractures.
AB  - A radial nerve injury associated with a humeral shaft fracture is an important
      injury pattern among trauma patients. It is the most common peripheral nerve
      injury associated with this fracture. Although treatment for this injury pattern
      is a controversial subject among upper-extremity surgeons, certain principles of
      management need to be applied in all cases. As our understanding of the
      pathoanatomy of the humerus and surrounding neurovascular structures has evolved,
      surgeons have adapted their strategies to improve outcome and avoid long-term
      morbidity. The principles of management and the clinical outcomes of various
      treatment strategies, defined in the literature, are reviewed in this article.

PMID- 16632063
TI  - Economic analysis in hand surgery.
AB  - Economic analysis is a method for allocating resources among competing
      alternatives. Four techniques commonly used in an economic analysis are cost
      minimization analysis, cost-effectiveness analysis, cost-benefit analysis, and
      cost-utility analysis. These analyses provide information to guide medical
      decisions and to set funding priorities. Understanding the differences between
      the techniques allows for better decision making. Although economic analysis is
      used widely in other fields of medicine, its use in studies of disorders of the
      hand has been sparse. Only recently has economic analysis been included in
      studies focused on the care of the upper-extremity patient. As such, to interpret
      the results of these studies better, hand surgeons need to understand the
      similarities and differences and the strengths and weaknesses of the different
      techniques. Such an understanding will allow hand surgeons to know when economic
      analyses are comparable. Furthermore it will aid them in providing their patients
      not only medically sound care, but also economically efficient care. This article
      provides a synopsis of the most widely used and accepted techniques for
      performing an economic analysis. The key concepts of each of the 4 techniques are
      shown by using the small number of studies that are available in the upper
      extremity literature.

PMID- 16632064
TI  - Magnetic resonance arthrography of the wrist: case presentation and discussion.

PMID- 16632066
TI  - Accessory branches of the dorsal cutaneous branch of the ulnar nerve revisited.

PMID- 16632067
TI  - Genetic and clinical characteristics of Korean maturity-onset diabetes of the
      young (MODY) patients.
AB  - Maturity-onset diabetes of the young (MODY) is mostly caused by mutations of the
      hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in
      Caucasians. But most Japanese and Chinese MODY patients are not linked to known
      MODY genes. In this study, we examined the genetic and clinical characteristics
      of Korean subjects with MODY and early onset type 2 diabetes who had been
      diagnosed before 15 years of age. The study included 23 unrelated subjects
      fulfilling the criteria for MODY (three consecutive generations of type 2
      diabetes with at least one member diagnosed under the age of 25 year) and 17
      unrelated subjects diagnosed with early onset type 2 DM under the age of 15
      years. The HNF-4alpha (MODY1), glucokinase (MODY2) and HNF-1alpha (MODY3) genes
      were analysed by direct sequencing. Mutations in the HNF-1alpha gene were found
      in two patients (5%). One of these, P393fsdelC, was novel, and was found in a
      patient classified in the MODY group. The GCK gene mutation, R191W, was
      identified in one patient classified as early-onset type 2 DM (2.5%). No
      mutations were found in the HNF-4alpha gene, except the T130I variant, which is a
      known rare polymorphism. In conclusion, the mutations in the HNF-1alpha gene and
      GCK account for a small proportion, about 5% and 2.5%, respectively, in Korean
      MODY and early onset type 2 patients. The majority of MODY cases in the Korean
      population are due to defects in unknown genes.

PMID- 16632068
TI  - Severe hearing loss in Dlxl mutant mice.
AB  - The Dlx homeobox gene family participates in regulating middle and inner ear
      development. A significant role for Dlxl, in particular,has been demonstrated in
      the development of the middle ear ossicles, but the functional consequences of
      Dlx.l gene mutation on hearing thresholds has not been assessed. The present
      study characterizes auditory brainstem responses to click and tonal stimuli in a
      non-lethal variant of a Dlxl gene knockout. We found that peripheral hearing
      thresholds for click and tonal stimuli were significantly elevated in homozygous
      Dlxl knockout (Dlxl-/ ) compared to both heterozygous (Dlxl+/ ) and wild type
      (Dlxl+/+) mice. Thus, abnormal mor-phogenesis of the incus and stapes that has
      been documented previously with histological measures is now known to result in a
      severe peripheral hearing deficit.

PMID- 16632069
TI  - Can better infrastructure and quality reduce hospital infant mortality rates in
      Mexico?
AB  - Preliminary evidence from hospital discharges hints enormous disparities in
      infant hospital mortality rates. At the same time, public health agencies
      acknowledge severe deficiencies and variations in the quality of medical services
      across public hospitals. Despite these concerns, there is limited evidence of the
      contribution of hospital infrastructure and quality in explaining variations in
      outcomes among those who have access to medical services provided at public
      hospitals. This paper provides evidence to address this question. We use
      probabilistic econometric methods to estimate the impact of material and human
      resources and hospital quality on the probability that an infant dies controlling
      for socioeconomic, maternal and reproductive risk factors. As a measure of
      quality, we calculate for the first time for Mexico patient safety indicators
      developed by the AHRQ. We find that the probability to die is affected by
      hospital infrastructure and by quality. In this last regard, having been treated
      in a hospital with the worse quality incidence doubles the probability to die.
      This paper also presents evidence on the contribution of other risk factors on
      perinatal mortality rates. The conclusions of this paper suggest that lower
      infant mortality rates can be reached by implementing a set of coherent public
      policy actions including an increase and reorganization of hospital
      infrastructure, quality improvement, and increasing demand for health by poor
      families.

PMID- 16632070
TI  - Traditional risk-sharing arrangements and informal social insurance in Eritrea.
AB  - In Eritrea neither the state nor the market is effective in providing health
      insurance to low-income people (in rural and informal job sector). Schemes
      intended for the informal sector are confronted with low and irregular incomes of
      target populations and consequently negligible potential for profit making.
      Because of this there, are no formal health insurance systems in Eritrea that
      cover people in the traditional (or informal) sector of the economy. In the
      absence of formal safety nets traditional Eritrean societies use their local
      social capital to alleviate unexpected social costs. In Eritrea traditional risk
      sharing arrangements are made within extended families and mutual aid community
      associations. This study reveals that in a situation where the state no longer
      provides free public health services any more and access to private insurance is
      denied, the extension of the voluntary mutual aid community associations to
      Mahber-based health insurance schemes at the local level is a viable way for
      providing modern health services.

PMID- 16632071
TI  - Public image and governance of epidemics: comparing HIV/AIDS and SARS.
AB  - A comparative analysis of the 2002-2003 infectious disease outbreak, severe acute
      respiratory syndrome (SARS), and the HIV/AIDS epidemic that has affected the
      world over the past two decades reveals the significant role of socio-cultural
      beliefs and attitudes in the shaping of people's lifestyles and approaches to the
      control and prevention of epidemics. The main research question is: what can we
      learn from the SARS experience about effective prevention of HIV/AIDS? The
      sources of data include population figures on the development of these epidemics
      and findings from two sociological studies of representative samples of
      Singapore's multi-ethnic population. The comparative study illustrates the impact
      of cultural beliefs and attitudes in shaping the public image of these two
      different infectious diseases; the relevance of public image of the disease for
      effective prevention and control of epidemics.

PMID- 16632072
TI  - User attitudes in analyzing digital slides in a quality control test bed: a
      preliminary study.
AB  - The pathologist examines suitably stained glass slides through a bright field
      microscope in order to render histopathological or cytological diagnosis by
      looking at tissues and cells. Glass slides serve as a permanent record of the
      patient disease. Over the course of a patient's treatment slides may need to be
      reviewed at other institutions before treatment can commence. Due to their
      fragile nature a transportable permanent digital facsimile of the glass slide
      would be ideal. A digital slide is a set of digital images representing the whole
      slide normally used by the pathologist, or a significant part of it; it is
      usually made by a large amount of images, up to thousands, which makes its
      management difficult. The present paper provides a description of the
      requirements needed to reproduce glass slides and of the available technological
      equipment, then the features of the two systems we implemented on different
      hardware are described, together with those of the digital slide viewer. The
      viewer was evaluated in two experimental test phases, during which user behaviour
      and diagnostic reports were measured. Digital slides used in the two experiments
      were acquired with either system. Possible applications of digital slides are
      then discussed, including undergraduate and professional education, quality
      control, and image analysis on full samples as well as on tissue microarrays.

PMID- 16632073
TI  - Night eating syndrome and winter seasonal affective disorder.
AB  - Night eating syndrome (NES) and winter seasonal affective disorder (SAD) share
      some features such as snacking for high-carbohydrate/high-fat food with increased
      weight, emotional distress, circadian disturbances, good response to
      serotoninergic antidepressants (SSRIs) and bright-light therapy. This study
      assessed the prevalence and socio-demographical and clinical correlates of the
      NES in a sample of 62 consecutive depressed outpatients with winter seasonal
      features (DSM-IV criteria). Depression was assessed with the 29 item-HDRS and
      Sigh-SAD version and with the 7-item depression subscale of the Hospital Anxiety
      and Depression scale. The prevalence of NES was low (4.8%). Patients suffering
      from NES were significantly older with a greater duration of the illness. NES was
      not related to depression and to Body Mass Index. NES and winter SAD are not
      overlapping disorders.

PMID- 16632074
TI  - Impact of surgeon-specific feedback on surgical site infection rates in Thailand.
AB  - Data on surgeon-specific feedback on surgical site infection (SSI) rates are not
      currently available in Thailand. The authors conducted a before and after study
      among patients undergoing surgery in seven Thai hospitals to examine whether a
      feedback system to surgeons could reduce SSI rates. After a six-month
      surveillance period, surgeons were provided with their own SSI rates and
      standardized infection ratios (SIRs). The criteria of the National Nosocomial
      Infection Surveillance (NNIS) system were used to determine SSI rates, and the
      SSI rates were compared with the NNIS report in terms of the SIR. To compare the
      SIR before and after intervention, the SIR ratio was calculated and logistic
      regression analysis was used to estimate the relative impact of surgeon-specific
      feedback, adjusting for patient sex, patient age, degree of wound contamination,
      American Society of Anesthesiologists' score, duration of operation, type of
      operation, use and duration of antibiotic prophylaxis, and length of pre
      operative stay. After confidential feedback to surgeons for six months, SSI rates
      and the SIR remained unchanged. The SSI rate in the pre-intervention period was
      1.7 infections/100 operations and the corresponding SIR was 0.8 [95% confidence
      intervals (CI)=0.6-0.9]. In the post-intervention period, the SSI rate was 1.8
      infections/100 operations, with a corresponding SIR of 0.8 (95%CI=0.7-0.9). The
      SIR ratio was 1.0. The relative risk of SSI after surgeon-specific feedback
      suggested that this intervention had no effect (adjusted relative risk=1.02,
      95%CI=0.77-1.35). Feedback to surgeons on their SSI rates did not reduce the
      rates of such infections in Thailand.

PMID- 16632075
TI  - Irish-1 and Irish-2: UK epidemic meticillin-resistant Staphylococcus aureus
      strains associated with Northern Ireland.
AB  - Since 1998, an increasing number of meticillin-resistant Staphylococcus aureus
      (MRSA) isolates with one of two characteristic phage patterns have been referred
      to the authors' laboratory from Northern Ireland. These strains were designated
      'Irish-1' and 'Irish-2'. Analysis of 956 submitted isolates classified as Irish-1
      or Irish-2 showed that 97% of the former and 95% of the latter were from Northern
      Ireland. Only 0.2% and 3%, respectively, were from England. Eleven Irish-2
      isolates had been referred from Western Australia as representatives of an
      epidemic strain originally isolated there in 1994. Ninety isolates with the Irish
      1 phage pattern and 91 isolates with the Irish-2 phage pattern, from numerous
      hospitals, were characterized by SmaI pulsed-field gel electrophoresis (PFGE),
      toxin gene carriage and antibiotic susceptibility. PFGE showed that, within each
      collection, a few isolates represented unrelated strains, but the majority were
      within six band differences of the most common profiles. Half of the Irish-1
      isolates were homogeneous, with 22 DNA profiles among the remainder. Irish-2
      isolates had two common profiles, D1 and D2, equally divided between one-third of
      the isolates and differing from each other by two bands; the remaining isolates
      shared 31 DNA profiles. Cluster analysis showed some overlap in DNA profiles
      between the Irish-1 and Irish-2 strains, but clear separation from other epidemic
      MRSA strains. There was no obvious correlation between PFGE profile and either
      antibiotic resistance pattern or toxin gene possession. All but three Irish-1
      isolates possessed only the staphylococcal enterotoxin A (sea) gene, whereas
      almost all Irish-2 isolates were negative for all 12 enterotoxin genes. Sixty
      nine percent of Irish-2 isolates were resistant to ciprofloxacin, erythromycin,
      kanamycin, neomycin and streptomycin, while 90% of Irish-1 isolates were
      resistant to all these plus gentamicin and mupirocin. All isolates were sensitive
      to quinupristin/dalfopristin, teicoplanin and vancomycin. Urease production was
      negative in both strains. The results suggest that Irish-1 and Irish-2 are
      distinct epidemic strains, identifiable by phage typing, DNA profiles, antibiotic
      resistance and toxin gene carriage.

PMID- 16632076
TI  - A practical tool to identify patients who may benefit from a palliative approach:
      the CARING criteria.
AB  - Palliative care is often offered only late in the course of disease after
      curative measures have been exhausted. To provide timelier symptom management,
      advance care planning, and spiritual support, we propose a simple set of
      prognostic criteria that identifies persons near the end of life. In this
      retrospective cohort study of five prognostic indicators, the CARING criteria
      (Cancer, Admissions > or = 2, Residence in a nursing home, Intensive care unit
      admit with multiorgan failure, > or = 2 Noncancer hospice Guidelines), logistic
      regression modeling demonstrated high sensitivity and specificity for mortality
      at 1 year (c statistic > 0.8). A simple set of clinically relevant criteria
      applied at the time of hospital admission can identify seriously ill persons who
      have a high likelihood of death in 1 year and, therefore, may benefit the most
      from incorporating palliative measures into the plan of care.

PMID- 16632077
TI  - Helping patients with advanced cancer live with concerns about eating: a
      challenge for palliative care professionals.
AB  - This paper reports findings of an exploratory study of the eating habits of
      people with advanced cancer living in the south of England in 2003. The purpose
      of the study was to develop an understanding of why eating can be experienced as
      troubling and examine the potential for helping people live with the changes in
      eating habits that often accompany advanced cancer. Semistructured interviews
      were conducted with 30 patients, 23 lay caregivers, and 14 specialist nurses. The
      data were analyzed thematically. It was found that patients experienced eating
      related concerns when the reality of eating differed from the expectations of
      eating. Patient response to concern ranged from acceptance to self-action. A
      subgroup of participants believed that they could have been helped by support for
      taking self-action. Eating-related concerns present nurses and other health care
      professionals with the challenge of supporting differing patient preferences for
      living with the symptom, which can include the expectation of support for self
      action.

PMID- 16632078
TI  - Knowledge and beliefs about end-of-life care and the effects of specialized
      palliative care: a population-based survey in Japan.
AB  - To clarify the knowledge and beliefs of the Japanese general population related
      to legal options, pain medications, communication with physicians, and
      hydration/nutrition in end-of-life care, and to explore the associations between
      end-of-life care they had experienced and these beliefs, a questionnaire survey
      was conducted on two target populations: 5000 general population subjects and 866
      bereaved family members of cancer patents who died in 12 palliative care units in
      Japan. The respondents were requested to report the legal knowledge about end-of
      life options, pain-related beliefs, communication-related beliefs, and
      hydration/nutrition-related beliefs, and their experiences with end-of-life care.
      A total of 3061 responses were analyzed (effective response rate, 54%). The
      respondents were classified into six groups: no bereavement experience (n = 949),
      those who had lost family members within the past 10 years from noncancer
      diseases at institutions (n = 673), those who lost family members from noncancer
      disease at home (n = 264), those who lost family members from cancer at
      institutions other than palliative care units (n = 525), those who lost family
      members from cancer at home (n = 86), and those who lost family members from
      cancer at palliative care units (n = 548). Across groups, 32-45% and 50-63% of
      the respondents stated that treatment withdrawal and double effect act were
      legal, respectively. Between 34% and 44% believed that cancer pain is not
      sufficiently relieved, 27-38% believed that opioids shorten life, and 24-33%
      believed that opioids cause addiction. Communication-related beliefs potentially
      resulting in barriers to satisfactory end-of-life discussion were identified in
      31-40% ("physicians are generally poor at communicating bad news") and in 14-25%
      ("physicians are not comfortable discussing death"). The bereaved family members
      of the patients who died in palliative care units were significantly more likely
      than the other groups to believe that cancer pain is sufficiently relieved, and
      significantly less likely to believe that opioids shorten life, that opioids
      cause addiction, that physicians are generally poor at communicating bad news,
      and that physicians are uncomfortable discussing death. Between 33% and 50% of
      the respondents, including families from palliative care units, believed
      "artificial hydration should be continued as the minimum standard until death,"
      while 15-31% agreed that "artificial hydration relieves patient symptoms." A
      significant proportion of the Japanese general population has beliefs about legal
      options, pain medications, and communication with physicians that potentially
      result in barriers to quality end-of-life care. As their experiences in
      specialized palliative care significantly influenced their belief, systematic
      efforts to spread quality palliative care activity are of value to lessen these
      barriers and achieve quality end-of-life care.

PMID- 16632079
TI  - Efficacy of darbepoetin alfa in alleviating fatigue and the effect of fatigue on
      quality of life in anemic patients with lymphoproliferative malignancies.
AB  - Anemia-related fatigue in cancer patients reduces health-related quality of life
      (HRQOL). These analyses evaluate the effect of hemoglobin level on fatigue and
      examine the relationship between improved fatigue and HRQOL. Data were collected
      during a multicenter, randomized trial involving 344 anemic patients with
      lymphoproliferative malignancies receiving chemotherapy and darbepoetin alfa or
      placebo. At baseline, interim study visits, and end of treatment, patients
      completed an HRQOL questionnaire. Improved hemoglobin levels were significantly
      associated (P < 0.001) with improved fatigue. Mean change in the Functional
      Assessment of Cancer Therapy (FACT) Fatigue score was 5.9 points greater when
      hemoglobin improved > 2 g/dl than when it declined. Patients experiencing a
      clinically meaningful improvement in fatigue reported significantly (P < 0.001)
      greater improvements in all other scales, except the FACT Social subscale.
      Managing anemia-related fatigue appears to have a positive impact on HRQOL,
      enhancing cancer patients' activity levels, mood, and perceived overall health.

PMID- 16632080
TI  - Symptom experience in Korean patients with liver cirrhosis.
AB  - This study was done to examine the level of symptom experience, and symptom
      variation in relation to demographic and clinical variables, in Korean patients
      with liver cirrhosis (LC). Symptom experience was measured using a scale
      developed by the researchers through a literature review on LC. Participants were
      129 patients whose mean age was 53.6 (standard deviation [SD] = 9.28) years. The
      results indicated that (1) overall symptom experience was relatively low (mean
      41.67, SD 24.71); (2) the main symptoms needing a management were fatigue,
      abdominal distension and/or peripheral edema, and muscle cramps; and (3) among
      the study variables, the severity of LC (P < 0.001) and the number of
      hospitalizations (P = 0.014) showed a significant relationship with overall
      symptom experience. These results suggest that symptom assessment requires a
      multidimensional approach and that it is imperative to consider disease severity
      in developing tailored symptom management programs for Korean patients with LC.

PMID- 16632081
TI  - Symptom prevalence and clustering of symptoms in people living with chronic
      hepatitis C infection.
AB  - Quality of life has been shown to be poor among people living with chronic
      hepatitis C. However, it is not clear how this relates to the presence of
      symptoms and their severity. The aim of this study was to describe the typology
      of a broad array of symptoms that were attributed to hepatitis C virus (HCV)
      infection. Phase 1 used qualitative methods to identify symptoms. In Phase 2, 188
      treatment-naive people living with HCV participated in a quantitative survey. The
      most prevalent symptom was physical tiredness (86%) followed by irritability
      (75%), depression (70%), mental tiredness (70%), and abdominal pain (68%).
      Temporal clustering of symptoms was reported in 62% of participants. Principal
      components analysis identified four symptom clusters: neuropsychiatric (mental
      tiredness, poor concentration, forgetfulness, depression, irritability, physical
      tiredness, and sleep problems); gastrointestinal (day sweats, nausea, food
      intolerance, night sweats, abdominal pain, poor appetite, and diarrhea); algesic
      (joint pain, muscle pain, and general body pain); and dysesthetic (noise
      sensitivity, light sensitivity, skin problems, and headaches). These data
      demonstrate that symptoms are prevalent in treatment-naive people with HCV and
      support the hypothesis that symptom clustering occurs.

PMID- 16632082
TI  - Validation study of the Korean version of the M. D. Anderson Symptom Inventory.
AB  - This study aimed to evaluate the Korean version of the M. D. Anderson Symptom
      Inventory (MDASI-K) as a tool for assessing multiple symptoms in Korean cancer
      patients. Participants (178 cancer patients and 178 age and sex-matched community
      dwelling adults) completed the MDASI-K and the Korean version of the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The MDASI-K
      exhibited substantial reliability and validity. Cronbach alpha coefficients were
      0.91 and 0.93 in the cancer patients, and 0.96 and 0.96 in the normal group for
      both symptom and interference, respectively. MDASI-K summary scores correlated
      significantly with those of the EORTC QLQ-C30. Discriminant validity of the MDASI
      K was demonstrated by its ability to clearly distinguish significant differences
      within different Eastern Cooperative Oncology Group performance statuses and
      those between the patient and normal groups in the mean scores of both symptom
      and interference. The MDASI-K is a valid and reliable measure for assessing
      multiple symptoms in Korean cancer patients.

PMID- 16632083
TI  - Validation of a Swedish version of the Cancer Dyspnea Scale.
AB  - The Cancer Dyspnea Scale (CDS) is a multidimensional measure of dyspnea
      experience, with three subscales related to sense of effort, sense of anxiety and
      sense of discomfort, and a total score. In this study, we evaluated the validity
      and reliability of a Swedish version, the CDS-S, in 99 patients with advanced
      lung cancer who were not receiving curative or life-prolonging treatments.
      Criterion-related validity was demonstrated by significant group differences in
      CDS-S scores when patients were stratified by dyspnea intensity, as measured by a
      visual analogue scale (VAS-D). Correlations between the total CDS-S score and
      other dyspnea scales varied between 0.63 and 0.68. Convergent validity was shown
      by comparing the CDS-S subscales with conceptually related measures of physical
      and emotional function and discomfort, and correlations ranged from 0.34 to 0.57.
      The CDS-S captured the psychological dimension of dyspnea better than did the VAS
      D. Internal consistency of the CDS-S scales was confirmed by Cronbach's alpha
      coefficients ranging from 0.81 to 0.90. The CDS-S was well received by the
      patients and completed in 2 minutes. This study supports the CDS as a valid and
      reliable instrument to measure dyspnea experience in a palliative setting, well
      suited for use in research as well as in clinical practice.

PMID- 16632084
TI  - Affective distress and amputation-related pain among older men with long-term,
      traumatic limb amputations.
AB  - Psychological distress and postamputation pain were investigated in a sample of
      582 males with long-term limb amputations (mean time since amputation 639.3
      months, standard deviation 166.1; range 240-784 months). Prevalence of
      significant depressive symptoms (Hospital Anxiety and Depression Scale [HADS]-D
      score > or = 8) was 32.0%, and 34.0% of respondents met the screening criterion
      for clinical anxiety (HADS-A score > or = 8). Nearly one quarter (24.6%) of
      respondents reported significant post-traumatic psychological stress symptoms
      (Impact of Event Scale scores > or = 35). In total, 87.8% experienced either
      phantom or residual limb pain. Affective distress scores differed according to
      the respondents' type of pain experience. Respondents who experienced residual
      limb pain reported significantly higher affective distress scores than those with
      no phantom or residual limb pain. Many older individuals with long-term traumatic
      limb amputations could benefit from interventions to ameliorate affective
      distress and appropriate residual limb pain treatment.

PMID- 16632085
TI  - Use of the cumulative proportion of responders analysis graph to present pain
      data over a range of cut-off points: making clinical trial data more
      understandable.
AB  - In randomized controlled trials, no single definition of response is ideal for
      all purposes. We propose a method to present in a simple fashion the likelihood
      of response over a full range of response levels, which will facilitate a better
      understanding of clinical trial data. We present the technique called the
      cumulative proportion of responders analysis (CPRA) and its application to four
      pain clinical trial data sets as examples. The CPRA can be used to present the
      proportion of responders over the entire range of possible cut-off points as a
      graph. This allows the reader to compare treatment groups at any responder level
      that is valid for their patient population. Whether as a primary or secondary
      approach to a clinical trial of pain therapy, the display of data in a CPRA
      format may be useful in the understanding of results and applicability to patient
      care.

PMID- 16632086
TI  - Effect of sustained limb ischemia on norepinephrine release from skeletal muscle
      sympathetic nerve endings.
AB  - Acute ischemia has been reported to impair sympathetic outflow distal to the
      ischemic area in various organs, whereas relatively little is known about this
      phenomenon in skeletal muscle. We examined how acute ischemia affects
      norepinephrine (NE) release at skeletal muscle sympathetic nerve endings. We
      implanted a dialysis probe into the adductor muscle in anesthetized rabbits and
      measured dialysate NE levels as an index of skeletal muscle interstitial NE
      levels. Regional ischemia was introduced by microsphere injection and ligation of
      the common iliac artery. The time courses of dialysate NE levels were examined
      during prolonged ischemia. Ischemia induced a decrease in the dialysate NE level
      (from 19+/-4 to 2.0+/-0 pg/ml, mean+/-S.E.), and then a progressive increase in
      the dialysate NE level. The increment in the dialysate NE level was examined with
      local administration of desipramine (DMI, a membrane NE transport inhibitor),
      omega-conotoxin GVIA (CTX, an N-type Ca(2+) channel blocker), or TMB-8 (an
      intracellular Ca(2+) antagonist). At 4h ischemia, the increment in the dialysate
      NE level (vehicle group, 143+/-30 pg/ml) was suppressed by TMB-8 (25+/-5 pg/ml)
      but not by DMI (128+/-10 pg/ml) or CTX (122+/-18 pg/ml). At 6h ischemia, the
      increment in the dialysate NE level was not suppressed by the pretreatment.
      Ischemia induced biphasic responses in the skeletal muscle. Initial reduction of
      NE release may be mediated by an impairment of axonal conduction and/or NE
      release function, while in the later phase, the skeletal muscle ischemia-induced
      NE release was partly attributable to exocytosis via intracellular Ca(2+)
      overload rather than opening of calcium channels or carrier mediated outward
      transport of NE.

PMID- 16632089
TI  - Developmental and metabolic disorders of the pancreas.
AB  - The pancreas is an important exocrine and endocrine organ that develops from the
      dorsal and ventral anlagen during embryogenesis and arises from the endodermal
      lining of the duodenum within the first month of human embryonic life. A number
      of developmental disorders can either lead to anatomic abnormalities of the
      pancreas and its ducts, or can be part of complex disorders that affect
      multiorgan systems. Other genetic changes can lead to metabolic abnormalities
      that affect the pancreas exclusively or increase the lifetime risk for developing
      pancreatitis or pancreatic diabetes. This article reviews some of the
      developmental and metabolic disorders that can affect the endocrine and exocrine
      pancreas.

PMID- 16632090
TI  - Genetic basis and pancreatic biology of Johanson-Blizzard syndrome.
AB  - The most recent elucidation of an inherited disorder of the pancreas concerns the
      Johanson-Blizzard syndrome (JBS). Positional cloning identified loss-of-function
      mutations in the UBRI gene on the long arm of chromosome 15 to be the cause of
      JBS in more than a dozen patients. In patients with JBS the absence of UBRI
      results in early prenatal destruction of the exocrine pancreas that involves
      impaired apoptosis, induced necrosis, and prominent inflammation. Knockout mice
      with absent UBR1 expression suffer from exocrine pancreatic insufficiency and
      increased susceptibility to experimental pancreatitis. The UBR1 protein
      substrate, presumably impaired degradation of which causes JBS, is not yet known.

PMID- 16632091
TI  - Polygenetic traits in pancreatic disorders.
AB  - Rapid advances in information and technology provide opportunities to discover
      the risks or causes for various disorders within individual patients. The
      availability of new data and new technology has outstripped the conceptual
      framework of simple disorders,however, and challenges current statistical
      approaches. The author addresses the issues surrounding study design and sample
      size for complex genetic traits with special attention to meta-analysis and
      systems biology. The author concludes that meta-analysis should play a limited
      role in evaluating studies of complex genetic diseases. Instead, systems biology
      based approaches should be developed to integrate multiple, focused, and
      mechanistic association studies, with the goal of assisting in the risk
      assessment of patients on a person-by-person basis.

PMID- 16632092
TI  - Trypsinogen mutations in pancreatic disorders.
AB  - There are multiple PRSS1 mutations described in hereditary pancreatitis but only
      a minority of these are clinically relevant. The two most frequent point
      mutations are in exon 2 (N29I) and exon3 (R122H), found in diverse racial
      populations. Both mutations result in early onset pancreatitis but the mechanism
      underlying this phenotype is unclear. The frequency of these mutations in such
      diverse populations suggests they have spontaneously occurred many times. The
      origin of the major mutations may be explained by gene conversions, accounting
      for multiple founders. The implications are discussed in terms of mechanism of
      action of the mutations and clinical presentation.

PMID- 16632093
TI  - Germline mutations and gene polymorphism associated with human pancreatitis.
AB  - A wide range of mutations and polymorphisms in genes that relate to pancreatic
      function seem to be involved in the development of pancreatitis. Some of these
      genetic alterations lead to disease phenotypes with unequivocal mendelian
      inheritance patterns, whereas others seem to act as modifier genes in conjunction
      with environ-mental or, as yet unidentified, genetic cofactors. This article
      reviews germline changes in the genes for trypsin, pancreatic secretory trypsin
      inhibitor, the cystic fibrosis conductance regulator, lipid metabolism proteins,
      inflammatory mediators for cytokines, and cathepsin B.

PMID- 16632095
TI  - Cell biology of pancreatic proteases.
AB  - More than 100 years ago it was proposed that pancreatitis essentially is a
      disease in which the pancreas undergoes autodigestion by its own prematurely
      activated digestive enzymes. Why and how digestive zymogens autoactivate within
      the pancreas early in the disease process has been a matter of controversy and
      debate. Some of the mechanisms that are considered to be involved indigestive
      protease activation are inherited and as of recently can be tested for
      clinically. Here we review the most recent progress in elucidating the mechanisms
      involved in the onset of pancreatitis. We specifically focus on serine and
      cysteine proteases in the autodigestive cascade that precedes acinar cell injury
      and the biochemical processes involved in their activation.

PMID- 16632094
TI  - Biochemical models of hereditary pancreatitis.
AB  - The past decade has witnessed remarkable progress in the genetics of chronic
      pancreatitis. Despite these accomplishments, the understanding of the molecular
      mechanisms through which PRSS1 and SPINK1 mutations cause chronic pancreatitis
      has remained sketchy. Pancreatitis-associated gene mutations are believed to
      result in uncontrolled trypsin activity in the pancreas. Experimental
      identification of the disease-relevant functional alterations caused by PRSS1 or
      SPINK1 mutations proved to be challenging, however, because results of
      biochemical analyses lent themselves to different interpretations. This article
      focuses on PRSS1 mutations and summarizes the salient biochemical findings in the
      context of the mechanistic models that explain the connection between mutations
      and hereditary pancreatitis.

PMID- 16632096
TI  - Biochemistry and biology of SPINK-PSTI and monitor peptide.
AB  - This article summarizes structural and functional properties of pancreatic
      secretory trypsin inhibitor (PSTI), which has been identified in many species.
      Its prominent role is to protect the pancreas from prematurely activated
      trypsinogen before entry into the duodenum. In the rat there are two isoforms,
      one of which is PSTI-I, a 61-amino acid peptide involved in the feedback
      regulation of pancreatic enzymes. Independent investigations in neoplastic
      diseases led to the discovery of tumor-associated trypsin inhibitor,which is
      identical to PSTI.

PMID- 16632097
TI  - Pathophysiology of SPINK mutations in pancreatic development and disease.
AB  - The endogenous pancreatic trypsin inhibitor, SPINK, is believed to limit enzyme
      activity in the pancreas and reduce the risk of pancreatitis. Recently, mutations
      in the SPINK1 gene have been associated with development of both acute and
      chronic pancreatitis. In most patients with SPINK1 mutations, the genetic
      variants do not cause the disease independently, but may act in concert with
      other genetic or environmental factors. Recent studies, using mice in which the
      trypsin inhibitor gene has been deleted or overexpressed, provide novel insights
      into the role of SPINK in pancreatic development and pancreatitis.

PMID- 16632098
TI  - Genes of type 2 diabetes in beta cells.
AB  - Type 2 diabetes is a complex polygenic metabolic disorder of epidemic
      proportions. This review provides a brief overview of the susceptibility genes in
      type 2 diabetes that primarily affect pancreatic 3 cells, with emphasis on their
      function and most relevant polymorphisms. We focus on calpain 10, the only
      susceptibility gene identified thus far through a positional cloning approach in
      subjects with diabetes.

PMID- 16632099
TI  - Genetic basis of maturity-onset diabetes of the young.
AB  - Most valuable breakthroughs in the genetics of type 2 diabetes mellitus have
      arisen from familial linkage analysis of maturity-onset diabetes of the young, an
      autosomal dominant form of diabetes typically occurring before 25 years of age
      and caused by primary insulin-secretion defects. Despite its low prevalence, MODY
      is not a single entity but presents genetic, metabolic, and clinical
      heterogeneity. MODY can result from mutations in at least six different genes;one
      encodes the glycolytic enzyme glucokinase, which is an important glucose sensor,
      whereas all the others encode transcription factors that participate in a
      regulatory network essential for adult beta cell function. Additional genes, yet
      unidentified, may explain the other MODY cases unlinked to a mutation in the
      known genes.

PMID- 16632100
TI  - New insights in the molecular pathogenesis of the maternally inherited diabetes
      and deafness syndrome.
AB  - The 3243A>G mutation in mitochondrial DNA (mtDNA) is a genetic variant that is
      associated with a high risk of developing diabetes during life. Enhanced aging of
      pancreatic beta-cells, a reduced capacity of these cells to synthesize large
      amounts of insulin,and a resetting of the ATP/ADP-regulated K-channel seem to be
      the pathogenic factors involved.

PMID- 16632101
TI  - Development of the pancreas and pancreatic cancer.
AB  - The pancreas is specified during embryonic development from the gut endoderm.
      Among the signaling pathways required for the proper development of the organ are
      the notch and hedgehog signaling pathways. Both of these pathways are reactivated
      in pancreatic cancers, and sustained hedgehog signaling is required for the
      viability of most pancreatic cancer cell lines. Further, mouse models of the
      disease show activation of these pathways, and expression of pancreas progenitor
      markers. These findings indicate that developmentally regulated gene expression
      programs are important in the pathogenesis of pancreatic cancer.

PMID- 16632102
TI  - Genotype/phenotype of familial pancreatic cancer.
AB  - It is estimated that 5% to 10% of pancreatic cancer cases are attributable to
      hereditary factors. We believe that the number of cases that are genetic in
      etiology are even greater, however, based not on a classic autosomal dominant
      pattern of inheritance but rather when one takes into account low-penetrant
      inherited susceptibility factors. There is also a growing recognition that the
      development of pancreatic cancer in pancreatic cancer-prone families is dependent
      not only on genetic variables but on nongenetic factors. The aim of this article
      is to review the challenges in identifying pancreatic cancer-prone families and
      how environmental factors interact with genetic factors in these families.

PMID- 16632103
TI  - Familial pancreatic cancer syndromes.
AB  - Hereditary pancreatic cancer (PC) is rare and extremely heterogeneous, and it
      accounts for approximately 2% of all PC cases. The major component of hereditary
      PC is the familial pancreatic cancer syndrome. Although up to 20% of hereditary
      PC cases are associated with germline mutations in the BRCA2, CDKN2A,
      PRSS1,STKI1, or MMR genes, the major underlying gene defect(s) is still unknown.
      Although hereditary PC is rare, the data on PC families that have been collected
      by various study groups worldwide provide a unique opportunity to evaluate the
      natural history, causative gene alterations, new diagnosis and chemoprevention
      strategies as well as treatment modalities.

PMID- 16632104
TI  - Endocrine tumors of the pancreas.
AB  - Neuroendocrine tumors of the pancreas are rare neoplasms of the heterogeneous
      group of neuroendocrine gastroenteropancreatic tumors that originate from
      totipotential stem cells or preexisting endocrine cells within the pancreas. Most
      neuroendocrine tumors of the pancreas are benign or show an indolent course of
      disease.A subset of them shows a very aggressive behavior, becomes highly
      malignant, and metastasizes early with life-limiting consequences. An effective
      disease-management includes the diagnostic approach with hormonal testing and
      localization and surgical treatment with histologic classification in combination
      with biotherapy, chemotherapy, or therapy with radionucleotides, de-pending on
      the individual behavior of the tumor. The primary goal is the improvement of
      symptoms leading to an acceptable quality of life in the individual patient.

PMID- 16632106
TI  - [Pollution and allergy].

PMID- 16632108
TI  - Innate and adaptive cellular immunity in flavivirus-naive human recipients of a
      live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3).
AB  - VDV3, a clonal derivative of the Mahidol live-attenuated dengue 3 vaccine was
      prepared in Vero cells. Despite satisfactory preclinical evaluation, VDV3 was
      reactogenic in humans. We explored whether immunological mechanisms contributed
      to this outcome by monitoring innate and adaptive cellular immune responses for
      28 days after vaccination. While no variations were seen in serum IL12 or
      TNFalpha levels, a high IFNgamma secretion was detected from Day 8, concomitant
      to IFNalpha, followed by IL10. Specific Th1 and CD8 responses were detected on
      Day 28, with high IFNgamma/TNFalpha ratios. Vaccinees exhibited very homogeneous
      class I HLA profiles, and a new HLA B60-restricted CD8 epitope was identified in
      NS3. We propose that, among other factors, adaptive immunity may have contributed
      to reactogenicity, even after this primary vaccination. In addition, the
      unexpected discordance observed between preclinical results and clinical outcome
      in humans led us to reconsider some of our preclinical acceptance criteria.
      Lessons learned from these results will help us to pursue the development of safe
      and immunogenic vaccines.

PMID- 16632109
TI  - Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing
      nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by
      receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor
      alpha.
AB  - The relationship between oxidative stress and bone mineral density or
      osteoporosis has recently been reported. As bone loss occurring in osteoporosis
      and inflammatory diseases is primarily due to increases in osteoclast number,
      reactive oxygen species (ROS) may be relevant to osteoclast differentiation,
      which requires receptor activator of nuclear factor-kappaB ligand (RANKL). Tumor
      necrosis factor-alpha (TNF-alpha) frequently present in inflammatory conditions
      has a profound synergy with RANKL in osteoclastogenesis. In this study, we
      investigated the effects of alpha-lipoic acid (alpha-LA), a strong antioxidant
      clinically used for some time, on osteoclast differentiation and bone resorption.
      At concentrations showing no growth inhibition, alpha-LA potently suppressed
      osteoclastogenesis from bone marrow-derived precursor cells driven either by a
      high-dose RANKL alone or by a low-dose RANKL plus TNF-alpha (RANKL/TNF-alpha).
      alpha-LA abolished ROS elevation by RANKL or RANKL/TNF-alpha and inhibited NF
      kappaB activation in osteoclast precursor cells. Specifically, alpha-LA reduced
      DNA binding of NF-kappaB but did not inhibit IKK activation. Furthermore, alpha
      LA greatly suppressed in vivo bone loss induced by RANKL or TNF-alpha in a
      calvarial remodeling model. Therefore, our data provide evidence that ROS plays
      an important role in osteoclast differentiation through NF-kappaB regulation and
      the antioxidant alpha-lipoic acid has a therapeutic potential for bone erosive
      diseases.

PMID- 16632110
TI  - Vitamin C fails to protect amino acids and lipids from oxidation during acute
      inflammation.
AB  - The observation that antioxidant vitamins fail to confer protective benefits in
      large, well-designed randomized clinical trials has led many to question the role
      of oxidative stress in the pathogenesis of disease. However, there is little
      evidence that proposed antioxidants actually scavenge reactive intermediates in
      vivo. Ascorbate reacts rapidly with oxidants produced by activated neutrophils in
      vitro, and neutrophils markedly increase their oxidant production when mice are
      infected intraperitoneally with the gram-negative bacterium Klebsiella
      pneumoniae. To explore the antioxidant properties of ascorbate in vivo, we
      therefore used K. pneumoniae infection as a model of oxidative stress. When mice
      deficient in L-gulono-gamma-lactone oxidase (Gulo(-/-)), the rate-limiting enzyme
      in ascorbate synthesis, were depleted of ascorbate and infected with K.
      pneumoniae, they were three times as likely as ascorbate-replete Gulo(-/-)mice to
      die from infection. Mass spectrometric analysis of peritoneal lavage fluid
      revealed a marked increase in the levels of oxidized amino acids and of F2
      isoprostanes (sensitive and specific markers of lipid oxidation) in infected
      animals. Surprisingly, there were no significant differences in the levels of the
      oxidation products in the ascorbate-deficient and -replete Gulo(-/-)mice. Our
      observations suggest that ascorbate plays a previously unappreciated role in host
      defense mechanisms against invading pathogens but that the vitamin does not
      protect amino acids and lipids from oxidative damage during acute inflammation.
      To examine the oxidation hypothesis of disease, optimal antioxidant regimens that
      block oxidative reactions in animals and humans need to be identified.

PMID- 16632111
TI  - Iron chelator induces THP-1 cell differentiation potentially by modulating
      intracellular glutathione levels.
AB  - Iron chelators have been implicated to modulate certain inflammatory mediators
      and regulate inflammatory processes. Here we report that iron chelator
      deferoxamine (DFO) induces differentiation of monocytic THP-1 cells into
      functional macrophages. DFO rapidly phosphorylated both extracellular signal
      regulated kinase (ERK) and p38 kinase. Blockade of ERK signaling by the MEK1/2
      inhibitor PD098059 abolished DFO-induced class A scavenger receptor (SR-A)
      expression and phagocytic activity, indicating that ERK cascades mediate the
      induction of THP-1 differentiation. In contrast, in cells treated with the p38
      inhibitor SB203580 or transfected with the dominant-negative variant of p38
      kinase, DFO-mediated ERK activation became more prominent, and the induction of
      SR-A expression and phagocytic activity were significantly increased.
      Interestingly, differentiation by DFO was associated with decrease in cellular
      glutathione (GSH) level. Both MAPK inhibitors did not influence the GSH level;
      however, treatment with ferric citrate (Fe3+) or N-acetyl-cysteine, a major
      precursor of GSH, markedly recovered GSH level to a normal extent, along with the
      significant decrease of differentiation. Collectively, these results indicate
      that oxidative stress by DFO and the resulting activation of ERK cascade play
      dominant roles in the process of THP-1 differentiation, while p38 acts as a
      negative signal transmitter.

PMID- 16632112
TI  - Involvement of selenoprotein P in protection of human astrocytes from oxidative
      damage.
AB  - Selenoprotein P (SeP) is a highly glycosylated, selenium-rich plasma protein.
      Aside from its role as selenium carrier protein, an antioxidative function of SeP
      has been suggested. Astrocytes, which detoxify reactive oxygen species in the
      brain, were described as potential target cells of SeP. We investigated the
      expression of SeP in human astrocytes and its involvement in the protection of
      these cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage. We
      show that primary human astrocytes and the human astrocytoma cell line MOG-G-CCM
      express SeP as an unglycosylated protein, which is not secreted. SeP expression
      in astrocytes is constitutive. Preincubation of astrocytes with hepatocyte
      derived SeP mimicks the protective effect of low-molecular-weight selenocompounds
      such as sodium selenite or selenomethionine against oxidative damage, shielding
      astrocytes from t-BHP-induced cytotoxicity. Selenium supplementation of
      astrocytes counteracts oxidative stress via an increase in expression and
      activity of the selenoenzyme cytosolic glutathione peroxidase (cGPx).
      Furthermore, specific downregulation of SeP expression by small interfering RNA
      decreases cell viability of human astrocytes and makes them more susceptible to t
      BHP-induced cytotoxicity. Our results implicate an antioxidant activity of
      constitutively expressed SeP in selenium-deficient astrocytes, while during
      adequate selenium supply the enhanced protection against oxidative stress is
      exerted by cGPx.

PMID- 16632113
TI  - The line asymmetry of electron spin resonance spectra as a tool to determine the
      cis:trans ratio for spin-trapping adducts of chiral pyrrolines N-oxides: the
      mechanism of formation of hydroxyl radical adducts of EMPO, DEPMPO, and DIPPMPO
      in the ischemic-reperfused rat liver.
AB  - Nonstereospecific addition of free radicals to chiral nitrones yields cis/trans
      diastereoisomeric nitroxides often displaying different electron spin resonance
      (ESR) characteristics. Glutathione peroxidase-glutathione (GPx-GSH) reaction was
      applied to reduce the superoxide adducts (nitrone/*OOH) to the corresponding
      hydroxyl radical (HO*) adducts (nitrone/*OH) of two nitrones increasingly used in
      biological spin trapping, namely 5-diethoxyphosphoryl-5-methyl-1-pyrroline N
      oxide (DEPMPO) and 5-ethoxycarbonyl-5-methyl-1-pyrroline N-oxide, and of 5
      diisopropoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DIPPMPO), a sterically
      hindered DEPMPO analogue. The method offered improved conditions to record highly
      resolved ESR spectra and by accurate simulation of line asymmetry we obtained
      clear evidence for the existence of previously unrecognized isomer pairs of cis-
      and trans-[DEPMPO/*OH] and [DIPPMPO/*OH]. Additional nitrone/*OH generation
      methods were used, i.e. photolysis of hydrogen peroxide and the Fenton reaction.
      We developed a kinetic model involving first- and second-order decay and a
      secondary conversion of trans to cis isomer to fully account for the strongly
      configuration-dependent behavior of nitrone/*OH. In the reductive system and, to
      a lower extent, in the Fenton or photolytic systems cis-nitrone/*OH was the more
      stable diastereoisomer. In various biologically relevant milieu, we found that
      the cis:trans-nitrone/*OH ratio determined right after the spin adduct formation
      significantly differed upon the GPx-GSH vs (Fenton or photolytic) systems of
      formation. This new mechanistic ESR index consistently showed for all nitrones
      that nitrone/*OH signals detected in the postischemic effluents of ischemic
      isolated rat livers are the reduction products of primary nitrone/*OOH. Thus, ESR
      deconvolution of cis/trans diastereoisomers is of great interest in the study of
      HO* formation in biological systems.

PMID- 16632114
TI  - Inhibition of cathepsins and related proteases by amino acid, peptide, and
      protein hydroperoxides.
AB  - Reaction of radicals in the presence of O2, and singlet oxygen, with some amino
      acids, peptides, and proteins yields hydroperoxides. These species are key
      intermediates in chain reactions and protein damage. Previously we have shown
      that peptide and protein hydroperoxides react rapidly with thiols, and that this
      can result in inactivation of thiol-dependent enzymes. The major route for the
      cellular removal of damaged proteins is via catabolism mediated by proteosomal
      and lysosomal pathways; cysteine proteases (cathepsins) play a key role in the
      latter system. We hypothesized that inactivation of cysteine proteases by
      hydroperoxide-containing oxidised proteins may contribute to the accumulation of
      modified proteins within cells. We show here that thiol-dependent cathepsins,
      either isolated or in cell lysates, are rapidly and efficiently inactivated by
      amino acid, peptide, and protein hydroperoxides in a time- and concentration
      dependent manner; this occurs with similar efficacy to equimolar H2O2.
      Inactivation involves reaction of the hydroperoxide with Cys residues as
      evidenced by thiol loss and formation of sulfenic acid intermediates.
      Structurally related, non-thiol-dependent cathepsins are less readily inactivated
      by these hydroperoxides. This inhibition, by oxidized proteins, of the system
      designed to remove modified proteins, may contribute to the accumulation of
      damaged proteins in cells subject to oxidative stress.

PMID- 16632115
TI  - Occurrence of trans fatty acids in rats fed a trans-free diet: a free radical
      mediated formation?
AB  - Trans isomers of unsaturated fatty acids are absorbed from the diet, due to their
      presence in diary fat and hydrogenated vegetable oils, and health concern has
      risen due to their effects on lipid risk factors in cardiovascular diseases. On
      the basis of the efficiency of the thiyl-radical-catalyzed cis/trans
      isomerization in vitro and the presence of many sulfur-containing compounds in
      the cell, the aim of this study was to demonstrate that trans geometry of lipid
      double bonds can be endogenously generated within membrane phospholipids. The
      study reports trans fatty acids occurrence in tissue and erythrocyte
      phospholipids of young adult rats fed a diet completely free of trans isomers.
      Results show that tissues are differently prone to the endogenous isomerization
      and that, following a free radical attack, trans fatty acids can reach very high
      amounts. The effectiveness of this process is considerably inhibited in the
      presence of all-trans retinol, confirming previous data in model membranes. Our
      results suggest that geometrical isomerization of unsaturated fatty acids, which
      causes a structural modification of membrane lipids and may influence basic
      membrane properties and vital biochemical functions, can occur under radical
      stress conditions and could be efficiently prevented by vitamin A.

PMID- 16632116
TI  - Up-regulation of gamma-glutamyl transpeptidase activity following glutathione
      depletion has a compensatory rather than an inhibitory effect on mitochondrial
      complex I activity: implications for Parkinson's disease.
AB  - Up-regulation of activity of gamma-glutamyl transpeptidase (GGT) has been
      reported to occur in the Parkinsonian substantia nigra, the area of the brain
      affected by the disease. Increased GGT activity has been hypothesized to play a
      role in subsequent mitochondrial complex I (CI) inhibition by increasing cysteine
      as substrate for cellular uptake. Intracellular cysteine has been proposed to
      form toxic adducts with dopamine which can be metabolized to compounds which
      inhibit CI activity. We have demonstrated that in addition to CI inhibition, GGT
      activity is up-regulated in dopaminergic cells as a consequence of glutathione
      depletion. Inhibition of GGT rather than resulting in increased CI inhibition
      results in exacerbation of this inhibitory effect. This suggests that increased
      GGT activity is likely an adaptive response to the loss of glutathione to
      conserve intracellular glutathione content and results in a compensatory effect
      on CI activity rather than in its inhibition as has been previously widely
      hypothesized.

PMID- 16632117
TI  - Protective effect of cyclic AMP against cisplatin-induced nephrotoxicity.
AB  - We reported earlier that reactive oxygen species are implicated in necrotic
      injury induced by a transient exposure of cultured renal tubular cells to a high
      concentration of cisplatin but not in apoptosis occurring after continuous
      exposure to a low concentration of cisplatin. We report here the protective
      effect of cyclic AMP against cisplatin-induced necrosis in cultured renal tubular
      cells as well as cisplatin-induced acute renal failure in rats. Several
      pharmacological agents that stimulate cyclic AMP signaling, including the
      nonhydrolyzable cyclic AMP analogue dibutyryl cyclic AMP, forskolin, 3-isobutyl-1
      methylxanthine, and a prostacyclin analogue, beraprost, prevented cisplatin
      induced cell injury in a protein kinase A-dependent manner. Cisplatin enhanced
      lipid peroxidation, decreased CuZn superoxide dismutase (SOD) while enhancing
      MnSOD activity, and increased cellular tumor necrosis factor-alpha (TNF-alpha)
      content. The elevation of TNF-alpha content and cell injury induced by cisplatin
      were attenuated by p38 mitogen-activated protein kinase (MAPK) inhibitors
      including SB203580 and PD169316. Indeed, cisplatin increased the number of
      phosphorylated p38 MAPK-like immunoreactive cells. These intracellular events
      were all reversed by antioxidants such as N-acetylcysteine (NAC) and glutathione
      or cyclic AMP analogues. The in vivo acute renal injury after cisplatin injection
      was associated with the elevation of renal TNF-alpha content. The cisplatin
      induced renal injury and the increase in TNF-alpha content were reversed by NAC
      or beraprost. These findings suggest that cyclic AMP protects renal tubular cells
      against cisplatin-induced oxidative injury by obliterating reactive oxygen
      species and subsequent inhibition of TNF-alpha synthesis through blockade of p38
      MAPK activation.

PMID- 16632118
TI  - 4-Hydroxynonenal inhibits telomerase activity and hTERT expression in human
      leukemic cell lines.
AB  - 4-Hydroxynonenal (HNE), produced during oxidative stress, has an
      antiproliferative/differentiative effect in several tumor cells. Recently, it has
      been observed that oxidative stress accelerates telomere loss. The length of
      telomeres depends on the telomerase activity, and the catalytic subunit of
      telomerase (hTERT) is strongly up-regulated in most human cancers and inhibited
      by differentiating agents. In this paper the inhibitory effect of HNE on
      telomerase activity and hTERT expression in three human leukemic cell lines (HL
      60, U937, ML-1) is reported. To investigate the molecular mechanism involved in
      hTERT down-regulation by HNE, the expression of several transcription factors was
      also studied: in all these cell lines, c-Myc was inhibited, Mad-1 was up
      regulated, and Sp-1 was not affected. Moreover, in p53 wild-type ML-1 cells, HNE
      up-regulated p53 expression. In HL-60 cells, DNA binding activity of c-Myc and
      Mad-1 to the E-box sequence of the hTERT promoter was inhibited and up-regulated,
      respectively. In summary, HNE inhibits telomerase activity via decreased hTERT
      promoter activity, by modulating c-Myc/Mad-1 transcription factor expression.

PMID- 16632119
TI  - Dietary fish oil alters cardiomyocyte Ca2+ dynamics and antioxidant status.
AB  - The n-3 polyunsaturated fatty acids (PUFAs) found in fish oil (FO) have been
      shown to protect against reperfusion arrhythmias, a manifestation of reperfusion
      injury, which is believed to be induced by the formation of reactive oxygen
      species (ROS) and intracellular calcium (Ca2+) overload. Adult rats fed a diet
      supplemented with 10% FO had a higher proportion of myocardial n-3 PUFAs and
      increased expression of antioxidant enzymes compared with the saturated fat (SF)
      supplemented group. Addition of hydrogen peroxide (H2O2) to cardiomyocytes
      isolated from rats in the SF-supplemented group increased the proportions of
      cardiomyocytes contracting in an asynchronous manner, increased the rate of Ca2+
      influx, and increased the diastolic and systolic [Ca2+]i compared with the FO
      group. H2O2 exposure increased the membrane fluidity of cardiomyocytes from the
      FO group. These results demonstrate that dietary FO supplementation is associated
      with a reduction in the susceptibility of myocytes to ROS-induced injury and this
      may be related to membrane incorporation of n-3 PUFAs, increased antioxidant
      defenses, changes in cardiomyocyte membrane fluidity, and the ability to prevent
      rises in cellular Ca2+ in response to ROS.

PMID- 16632120
TI  - Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and
      activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes.
AB  - Solar ultraviolet (UV) radiation-induced oxidative stress has been implicated in
      various skin diseases. Here, we report the photoprotective effect of grape seed
      proanthocyanidins (GSPs) on UV-induced oxidative stress and activation of mitogen
      activated protein kinase (MAPK) and NF-kappaB signaling pathways using normal
      human epidermal keratinocytes (NHEK). Treatment of NHEK with GSPs inhibited UVB
      induced hydrogen peroxide (H2O2), lipid peroxidation, protein oxidation, and DNA
      damage in NHEK and scavenged hydroxyl radicals and superoxide anions in a cell
      free system. GSPs also inhibited UVB-induced depletion of antioxidant defense
      components, such as glutathione peroxidase, catalase, superoxide dismutase, and
      glutathione. As UV-induced oxidative stress mediates activation of MAPK and NF
      kappaB signaling pathways, we determined the effects of GSPs on these pathways.
      Treatment of NHEK with GSPs inhibited UVB-induced phosphorylation of ERK1/2, JNK,
      and p38 proteins of the MAPK family at the various time points studied. As UV
      induced H2O2 plays a major role in activation of MAPK proteins, NHEK were treated
      with H2O2 with or without GSPs and other known antioxidants, viz. (-)
      epigallocatechin-3-gallate, silymarin, ascorbic acid, and N-acetylcysteine. It
      was observed that H2O2-induced phosphorylation of ERK1/2, JNK, and p38 was
      decreased by these antioxidants. Under identical conditions, GSPs also inhibited
      UVB-induced activation of NF-kappaB/p65, which was mediated through inhibition of
      degradation and activation of IkappaBalpha and IKKalpha, respectively. Together,
      these results suggest that GSPs could be useful in the attenuation of UV
      radiation-induced oxidative stress-mediated skin diseases in human skin.

PMID- 16632121
TI  - Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL
      60 cells.
AB  - As a reducing agent, ascorbate serves as an antioxidant. However, its reducing
      function can in some settings initiate an oxidation cascade, i.e., seem to be a
      "pro-oxidant." This dichotomy also seems to hold when ascorbate is present during
      photosensitization. Ascorbate can react with singlet oxygen, producing hydrogen
      peroxide. Thus, if ascorbate is present during photosensitization the formation
      of highly diffusible hydrogen peroxide could enhance the toxicity of the
      photodynamic action. On the other hand, ascorbate could decrease toxicity by
      converting highly reactive singlet oxygen to less reactive hydrogen peroxide,
      which can be removed via peroxide-removing systems such as glutathione and
      catalase. To test the influence of ascorbate on photodynamic treatment we
      incubated leukemia cells (HL-60 and U937) with ascorbate and a photosensitizer
      (Verteporfin; VP) and examined ascorbic acid monoanion uptake, levels of
      glutathione, changes in membrane permeability, cell growth, and toxicity.
      Accumulation of VP was similar in each cell line. Under our experimental
      conditions, HL-60 cells were found to accumulate less ascorbate and have lower
      levels of intracellular GSH compared to U937 cells. Without added ascorbate, HL
      60 cells were more sensitive to VP and light treatment than U937 cells. When
      cells were exposed to VP and light, ascorbate acted as an antioxidant in U937
      cells, whereas it was a pro-oxidant for HL-60 cells. One possible mechanism to
      explain these observations is that HL-60 cells express myeloperoxidase activity,
      whereas in U937 cells it is below the detection limit. Inhibition of
      myeloperoxidase activity with 4-aminobenzoic acid hydrazide (4-ABAH) had minimal
      influence on the phototoxicity of VP in HL-60 cells in the absence of ascorbate.
      However, 4-ABAH decreased the toxicity of ascorbate on HL-60 cells during VP
      photosensitization, but had no affect on ascorbate toxicity in U937 cells. These
      data demonstrate that ascorbate increases hydrogen peroxide production by VP and
      light. This hydrogen peroxide activates myeloperoxidase, producing toxic
      oxidants. These observations suggest that in some settings, ascorbate may enhance
      the toxicity of photodynamic action.

PMID- 16632122
TI  - The acute-phase response of the liver in relation to thyroid hormone-induced
      redox signaling.
AB  - Recently, we reported that 3,3',5-triiodothyronine (T3) induces the expression of
      redox-sensitive genes as a nongenomic mechanism of T3 action. In this study, we
      show that T3 administration to rats (daily doses of 0.1 mg/kg ip for 3
      consecutive days) induced a calorigenic response and liver glutathione depletion
      as an indication of oxidative stress, with higher levels of interleukin (IL)-6 in
      serum (ELISA) and hepatic STAT3 DNA binding (EMSA), which were maximal at 48-72 h
      after treatment. Under these conditions, the protein expression of the acute
      phase proteins haptoglobin and beta-fibrinogen is significantly augmented, a
      change that is suppressed by pretreatment with alpha-tocopherol (100 mg/kg ip) or
      gadolinium chloride (10 mg/kg iv) before T3. It is concluded that T3
      administration induces the acute-phase response in rat liver by a redox mechanism
      triggered at the Kupffer cell level, in association with IL-6 release and
      activation of the STAT3 cascade, a response that may contribute to reestablishing
      homeostasis in the liver and extrahepatic tissues exhibiting oxidative stress.

PMID- 16632123
TI  - Concentrations of iron correlate with the extent of protein, but not lipid,
      oxidation in advanced human atherosclerotic lesions.
AB  - Previous studies have provided compelling evidence for the presence of oxidized
      proteins and lipids in advanced human atherosclerotic lesions. The catalyst
      responsible for such oxidation is unknown and controversial. We have previously
      provided evidence for elevated levels of iron in lesions. In this study we
      hypothesized that if iron ions catalyzed protein and lipid oxidation in the
      artery wall, then there should be a positive correlation between these
      parameters. Iron concentrations in ex vivo healthy human arteries and advanced
      carotid lesions were quantified by electron paramagnetic resonance spectroscopy.
      Four specific side-chain oxidation products of proteins, and the lipid oxidation
      products 7-ketocholesterol and cholesterol ester alcohols and hydroperoxides,
      were quantified by HPLC in the same samples used for the iron measurements.
      Parent amino acids, cholesterol, and cholesterol esters were also quantified.
      Statistically elevated levels of iron, cholesterol, cholesterol esters, 7
      ketocholesterol, and cholesterol ester alcohols and hydroperoxides were detected
      in advanced lesions compared with healthy control tissue. Iron levels correlated
      positively and strongly with all four markers of protein oxidation, but not with
      either marker of lipid oxidation. These data support the hypothesis that elevated
      levels of iron contribute to the extent of protein, but not lipid, oxidation in
      advanced human lesions.

PMID- 16632124
TI  - A new terbium(III) chelate as an efficient singlet oxygen fluorescence probe.
AB  - A terbium(III) chelate fluorescence probe for detection of singlet oxygen (1O2)
      in aqueous media, N,N,N1,N1-[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4-(9''
      anthryl)pyridine] tetrakis (acetate)-Tb3+ (PATA-Tb3+), was designed and
      synthesized. The new chelate is highly water soluble, is almost nonfluorescent,
      and can specifically react with 1O2 to yield a strongly fluorescent chelate, the
      endoperoxide of PATA-Tb3+, accompanied by a remarkable increase in the
      fluorescence quantum yield from 0.46 to 10.5%. The long fluorescence lifetime of
      the endoperoxide (2.76 ms) allows the probe to be used favorably for time
      resolved fluorescence detection of 1O2. The studies of fluorescence property and
      reaction specificity indicate that the new probe is highly sensitive and
      selective for 1O2. The probe was used for quantitative detection of 1O2 generated
      from a MoO4(2-) -H2O2 system to give a detection limit of 10.8 nM. In addition,
      the good applicability of the probe was demonstrated by the real-time monitoring
      of the kinetic process of 1O2 generation in a horseradish peroxidase-catalyzed
      oxidation system of indole-3-acetic acid in a weakly acidic buffer.

PMID- 16632125
TI  - Metalloprotein-dependent decomposition of S-nitrosothiols: studies on the
      stabilization and measurement of S-nitrosothiols in tissues.
AB  - The stabilization of S-nitrosothiols is critical for the development of assays to
      measure their concentration in tissues. Low-molecular-weight S-nitrosothiols are
      unstable in tissue homogenates, even in the presence of thiol blockers or metal
      ion chelators. The aim of this study was to try and stabilize low-molecular
      weight S-nitrosothiols in tissue and gain insight into the mechanisms leading to
      their decomposition. Rat tissues (liver, kidney, heart, and brain) were perfused
      and homogenized in the presence of a thiol-blocking agent (N-ethylmaleimide) and
      a metal-ion chelator (DTPA). Incubation of liver homogenate with low-molecular
      weight S-nitrosothiols (L-CysNO, D-CysNO, and GSNO) resulted in their rapid
      decomposition in a temperature-dependent manner as measured by chemiluminescence.
      The decomposition of L-CysNO requires a cytoplasmic factor, with activity
      greatest in liver > kidney > heart > brain > plasma, and is inhibitable by
      enzymatic proteolysis or heating to 80 degrees C, suggesting that a protein
      catalyzes the decomposition of S-nitrosothiols. The ability of liver homogenate
      to catalyze the decomposition of L-CysNO is up-regulated during endotoxemia and
      is dependent on oxygen, with the major product being nitrate. Multiple agents
      were tested for their ability to block the decomposition of L-CysNO without
      success, with the exception of potassium ferricyanide, which completely blocked
      CysNO decomposition in liver homogenates. This suggests that a ferrous protein
      (or group of ferrous proteins) may be involved. We also show that homogenization
      of tissues in ferricyanide-containing buffers in the presence of N-ethylmaleimide
      and DTPA can stabilize both low- and high-molecular-weight S-nitrosothiols in
      tissues before the measurement of their concentration.

PMID- 16632126
TI  - Notoginsenoside R1 inhibits TNF-alpha-induced fibronectin production in smooth
      muscle cells via the ROS/ERK pathway.
AB  - The matrix fibronectin protein plays an important role in vascular remodeling.
      Notoginsenoside R1 is the main ingredient with cardiovascular activity in Panax
      notoginseng; however, its molecular mechanisms are poorly understood. We report
      that notoginsenoside R1 significantly decreased TNF-alpha-induced activation of
      fibronectin mRNA, protein levels, and secretion in human arterial smooth muscle
      cells (HASMCs) in a dose-dependent manner. Notoginsenoside R1 scavenged hydrogen
      peroxide (H2O2) in a dose-dependent manner in the test tube. TNF-alpha
      significantly increased intracellular ROS generation and then ERK activation,
      which was blocked by notoginsenoside R1 or DPI and apocynin, inhibitors of NADPH
      oxidase, or the antioxidant NAC. Our data demonstrated that TNF-alpha-induced
      upregulation of fibronectin mRNA and protein levels occurs via activation of
      ROS/ERK, which was prevented by treatment with notoginsenoside R1, DPI, apocynin,
      NAC, or MAPK/ERK inhibitors PD098059 and U0126. Notoginsenoside R1 significantly
      inhibited H2O2-induced upregulation of fibronectin mRNA and protein levels and
      secretion; it also significantly inhibited TNF-alpha and H2O2-induced migration.
      These results suggest that notoginsenoside R1 inhibits TNF-alpha-induced ERK
      activation and subsequent fibronectin overexpression and migration in HASMCs by
      suppressing NADPH oxidase-mediated ROS generation and directly scavenging ROS.

PMID- 16632127
TI  - Rat liver-mediated metabolism of hydroxyurea to nitric oxide.
AB  - Hydroxyurea is an approved treatment for sickle cell disease. Oxidation of
      hydroxyurea results in the formation of nitric oxide (NO), which also has drawn
      considerable interest as a sickle cell disease therapy. Although patients on
      hydroxyurea demonstrate elevated levels of nitric oxide-derived metabolites,
      little information regarding the site or mechanism of the in vivo conversion of
      hydroxyurea to nitric oxide exists. Chemiluminescence detection experiments show
      the ability of crude rat liver homogenate to convert hydroxyurea to
      nitrite/nitrate, evidence for NO production. Nitrite/nitrate form at therapeutic
      concentrations of hydroxyurea in a clinically relevant time frame. Electron
      paramagnetic resonance (EPR) studies show the formation of iron nitrosyl
      complexes during this incubation and experiments with labeled hydroxyurea show
      the NO derives from the drug. Gas chromatography-mass spectrometry measurements
      indicate the hydrolysis of hydroxyurea to hydroxylamine in this system.
      Incubation of hydroxylamine with crude rat liver homogenate also generates
      nitrite/nitrate and iron nitrosyl complexes. A line of evidence including
      inhibitor studies, EPR spectroscopy, and nitrite/nitrate detection identifies
      catalase as a possible oxidant for the conversion of hydroxyurea to NO. These
      results reveal the ability of liver tissue to convert hydroxyurea to nitric oxide
      and provide insight into the metabolism of this drug.

PMID- 16632128
TI  - In vivo measurements of subacromial impingement: substantial compression develops
      in abduction with large internal rotation.
AB  - BACKGROUND: Subacromial impingement is a widely recognized mechanism of chronic
      shoulder pain. The magnitudes of the compressive forces that impinge the
      subacromial structures were often measured from cadaveric specimens, but it is
      questionable to use this data as a sole basis to determine the shoulder motions
      and/or shoulder configurations that induce impingement in live subjects
      performing active motion. The purpose of the present study was to determine in
      vivo the magnitude of the compressive force at selected shoulder configurations.
      METHODS: The subacromial structures may be impinged by the downward-directed
      forces exerted by the coraco-acromial ligament. The reactions of these forces
      push the ligament upwards and deform it into a curved shape. A single resultant
      of these reaction forces was determined with an inverse approach to quantify the
      magnitude of the impingement force. An ultrasound unit was used to visualize the
      deformed shape of the coraco-acromial ligament for thirteen subjects with no
      symptomatic shoulder problem actively holding their shoulders in five
      configurations. FINDINGS: The impingement force in 90 degrees abduction+maximum
      internal rotation (mean=21.3N) and that in the Hawkins test position (mean=18.3N)
      were significantly greater than those in 90 degrees abduction+neutral and
      external rotation (means < or = 3N). INTERPRETATION: For young asymptomatic
      shoulders, the motions that induce impingement are not any arm abduction, but the
      arm abduction with a large internal rotation. Further study is indicated to
      examine the impingement force among various age groups.

PMID- 16632129
TI  - Sorption, degradation and mobility of microcystins in Chinese agriculture soils:
      Risk assessment for groundwater protection.
AB  - In the present paper, sorption, persistence, and leaching behavior of three
      microcystin variants in Chinese agriculture soils were examined. Based on this
      study, the values of capacity factor and slope for three MCs variants in three
      soils ranged from 0.69 to 6.00, and 1.01 to 1.54, respectively. The adsorption of
      MCs in the soils decreased in the following order: RR > Dha7 LR > LR.
      Furthermore, for each MC variant in the three soils, the adsorption rate in the
      soils decreased in the following order: soil A > soil C > soil B. The calculated
      half-time ranged between 7.9 and 17.8 days for MC-RR, 6.0-17.1 days for MC-LR,
      and 7.1-10.2 days for MC-Dha7 LR. Results from leaching experiments demonstrated
      that recoveries of toxins in leachates ranged from 0-16.7% for RR, 73.2-88.9% for
      LR, and 8.9-73.1% for Dha7 LR. The GUS value ranged from 1.48 to 2.06 for RR,
      1.82-2.88 for LR, and 1.76-2.09 for Dha7 LR. Results demonstrated the use of
      cyanobacterial collections as plant fertilizer is likely to be unsafe in soils.

PMID- 16632130
TI  - Effect of reactive media composition and co-contaminants on sulfur-based
      autotrophic denitrification.
AB  - As a part of a study developing a biological reactive barrier system to treat
      nitrate-contaminated groundwater, the effects of reactive media composition and
      co-contaminants on sulfur-oxidizing autotrophic denitrification were
      investigated. The size of sulfur granules affected the denitrification rates;
      kinetic constants of 2.883, 2.949, and 0.677 mg-N(1/2)/L(1/2)/day were obtained
      when the granule sizes were below 2 mm, between 2 and 5 mm, and over 5 mm,
      respectively. When the volume ratios of sulfur to limestone were 1:1, 2:1, 3:1,
      and 4:1, kinetic constants of 5.490, 3.903, 4.072, and 2.984 mg-N(1/2)/L(1/2)/day
      were obtained, respectively. The presence of TCE up to 20 mg/L didn't
      significantly affect nitrate removal efficiency. At the TCE concentration of 80
      mg/L, however, nitrate removal was markedly inhibited. Also, Zn and Cu inhibited
      the denitrification activity at more than 0.5 mg/L of concentration whereas Cr
      (VI) did not significantly affect the nitrate removal efficiency at all levels
      tested.

PMID- 16632132
TI  - Ordinal regression model and the linear regression model were superior to the
      logistic regression models.
AB  - OBJECTIVE: Ordinal scales often generate scores with skewed data distributions.
      The optimal method of analyzing such data is not entirely clear. The objective
      was to compare four statistical multivariable strategies for analyzing skewed
      health-related quality of life (HRQOL) outcome data. HRQOL data were collected at
      1 year following catheterization using the Seattle Angina Questionnaire (SAQ), a
      disease-specific quality of life and symptom rating scale. STUDY DESIGN AND
      SETTING: In this methodological study, four regression models were constructed.
      The first model used linear regression. The second and third models used logistic
      regression with two different cutpoints and the fourth model used ordinal
      regression. To compare the results of these four models, odds ratios, 95%
      confidence intervals, and 95% confidence interval widths (i.e., ratios of upper
      to lower confidence interval endpoints) were assessed. RESULTS: Relative to the
      two logistic regression analysis, the linear regression model and the ordinal
      regression model produced more stable parameter estimates with smaller confidence
      interval widths. CONCLUSION: A combination of analysis results from both of these
      models (adjusted SAQ scores and odds ratios) provides the most comprehensive
      interpretation of the data.

PMID- 16632133
TI  - Small-scale randomized controlled trials need more powerful methods of
      mediational analysis than the Baron-Kenny method.
AB  - OBJECTIVE: To devise more-effective physical activity interventions, the
      mediating mechanisms yielding behavioral change need to be identified. The Baron
      Kenny method is most commonly used, but has low statistical power and may not
      identify mechanisms of behavioral change in small-to-medium size studies. More
      powerful statistical tests are available. STUDY DESIGN AND SETTING: Inactive
      adults (N=52) were randomized to either a print or a print-plus-telephone
      intervention. Walking and exercise-related social support were assessed at
      baseline, after the intervention, and 4 weeks later. The Baron-Kenny and three
      alternative methods of mediational analysis (Freedman-Schatzkin; MacKinnon et
      al.; bootstrap method) were used to examine the effects of social support on
      initial behavior change and maintenance. RESULTS: A significant mediational
      effect of social support on initial behavior change was indicated by the
      MacKinnon et al., bootstrap, and, marginally, Freedman-Schatzkin methods, but not
      by the Baron-Kenny method. No significant mediational effect of social support on
      maintenance of walking was found. CONCLUSIONS: Methodologically rigorous
      intervention studies to identify mediators of change in physical activity are
      costly and labor intensive, and may not be feasible with large samples. The use
      of statistically powerful tests of mediational effects in small-scale studies can
      inform the development of more effective interventions.

PMID- 16632131
TI  - A review of the application of propensity score methods yielded increasing use,
      advantages in specific settings, but not substantially different estimates
      compared with conventional multivariable methods.
AB  - OBJECTIVE: Propensity score (PS) analyses attempt to control for confounding in
      nonexperimental studies by adjusting for the likelihood that a given patient is
      exposed. Such analyses have been proposed to address confounding by indication,
      but there is little empirical evidence that they achieve better control than
      conventional multivariate outcome modeling. STUDY DESIGN AND METHODS: Using
      PubMed and Science Citation Index, we assessed the use of propensity scores over
      time and critically evaluated studies published through 2003. RESULTS: Use of
      propensity scores increased from a total of 8 reports before 1998 to 71 in 2003.
      Most of the 177 published studies abstracted assessed medications (N=60) or
      surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90).
      Whether PS methods or conventional outcome models were used to control for
      confounding had little effect on results in those studies in which such
      comparison was possible. Only 9 of 69 studies (13%) had an effect estimate that
      differed by more than 20% from that obtained with a conventional outcome model in
      all PS analyses presented. CONCLUSIONS: Publication of results based on
      propensity score methods has increased dramatically, but there is little evidence
      that these methods yield substantially different estimates compared with
      conventional multivariable methods.

PMID- 16632134
TI  - Self-rated health showed a graded association with frequently used biomarkers in
      a large population sample.
AB  - BACKGROUND AND OBJECTIVES: Self-rated health is a widely used measure of health
      status, but its biologic foundations are poorly understood. We investigated the
      association of frequently used biomarkers with self-rated health, and the role of
      these biomarkers in the association of self-rated health with mortality. METHODS:
      The relation of self-rated health to blood levels of albumin, white blood cell
      count, hemoglobin, HDL cholesterol, and creatinine was examined in a population
      based sample of 4,065 men and women aged 71 years or older. A Cox proportional
      hazards model was used to determine the association of self-rated health with
      mortality during 4.9 years. Sociodemographic factors, diagnosed chronic
      conditions, and activities of daily living disability were controlled for in
      these analyses. RESULTS: All the biomarkers showed a graded relationship with
      self-rated health. After adjusting for other indicators, hemoglobin and white
      cell count were significantly associated with fair or poor self-rated health.
      When biomarkers and other indicators were adjusted for, self-rated health still
      was a significant predictor of mortality. CONCLUSION: Self-rated health has a
      biologic basis, and it can be a sensitive barometer of physiologic states. Self
      rated health is likely to predict mortality because it covers the spectrum of
      health conditions better than the variables measured in the study.

PMID- 16632135
TI  - Health Utilities Index mark 3 demonstrated construct validity in a population
      based sample with type 2 diabetes.
AB  - OBJECTIVE: To assess the cross-sectional construct validity of the Health
      Utilities Index mark 3 (HUI3) in type 2 diabetes using population health survey
      data. STUDY DESIGN AND SETTING: Data used were from 5,134 adult respondents of
      Cycle 1.1 (2000-2001) of the Canadian Community Health Survey (CCHS) with type 2
      diabetes. Analyses of covariance models were used to assess differences in
      overall and single-attribute HUI3 scores between groups hypothesized a priori to
      differ in HRQL. The association between health-care resource use (i.e.,
      hospitalizations and physician and emergency room visits) and overall HUI3 scores
      was assessed using logistic regression models. RESULTS: For overall HUI3 scores,
      clinically important and statistically significant differences were observed
      between all groups expected to differ in HRQL. Depression was the comorbidity
      associated with the largest deficit (-0.17; 95% confidence interval CI=-0.22, 
      0.12), followed by stroke (-0.15; 95% CI=-0.21, -0.10) and heart disease (-0.08;
      95% CI=-0.11, -0.05). Insulin use and comorbidities were associated with
      clinically important deficits in pain. Overall HUI3 scores were significantly
      predictive of all three categories of health-care resource use. CONCLUSION:
      Observed differences between groups contribute further evidence of the construct
      validity of the HUI3 in type 2 diabetes.

PMID- 16632136
TI  - A 37-item shoulder functional status item pool had negligible differential item
      functioning.
AB  - OBJECTIVE: Measures of shoulder function may differ by dominance of affected
      shoulder, surgical history, gender, or race. We present a technique for
      determining whether observed differences in function between groups are due to
      biased test items or real differences in function. STUDY DESIGN AND SETTING: Four
      hundred patients who were receiving rehabilitation for a variety of shoulder
      impairments completed a survey of shoulder function. Thirty-seven items measuring
      shoulder function were analyzed for differential item functioning (DIF) related
      to demographic characteristics using an ordinal logistic regression (OLR) and
      item response theory (IRT) approach. When DIF was identified in an item, we
      modified the IRT analysis to calibrate item parameters separately in appropriate
      demographic groups. We compared adjusted and unadjusted patient ability measures
      in each demographic group. RESULTS: Several items were found to have a modest
      amount of DIF related to the different demographic characteristics, especially
      gender; however, adjusting measures for DIF had little impact on overall measures
      of shoulder function and made almost no difference in average shoulder function
      across demographic groups. CONCLUSION: In this pool of shoulder function items,
      adjustment for DIF made almost no difference in measures of function across
      demographic groups.

PMID- 16632137
TI  - Eight predictive factors associated with response patterns during physiotherapy
      for soft tissue shoulder disorders were identified.
AB  - BACKGROUND AND OBJECTIVE: Combining information on initial and final state with
      information on speed of response may reflect the clinical reality of the course
      of recovery from soft tissue shoulder disorders. The purpose was to identify
      baseline factors that predict patterns of response to physiotherapy. STUDY DESIGN
      AND SETTING: Prospective cohort of consecutive clients (n=361) with soft tissue
      shoulder disorders attending physiotherapy. A previous study identified four
      typical patterns of response such that each individual was assigned to one of
      four clusters (dependent outcome). Independent predictors (n=28) included
      demographics, disorder-related and disability measures, treatment factors,
      clinical findings, and expectations for recovery. Multivariable multinomial
      logistic regression techniques were used. RESULTS: Predictors differentiating
      patterns of response were: Age (by decade), duration of current shoulder problem,
      worker's compensation claim, client's global rating of problem, Physical
      Component Score (SF-36), Mental Component Score (SF-36), over the counter
      medication use, and therapist prediction of client to return to usual activity.
      CONCLUSION: Using a clinically sensible outcome, we have identified several
      predictors that can be used by clinicians in clinical decision making.

PMID- 16632138
TI  - A randomized database study in general practice yielded quality data but patient
      recruitment in routine consultation was not practical.
AB  - OBJECTIVE: To assess patient recruitment and quality of data in a randomized
      database study. STUDY DESIGN AND SETTING: A randomized database study was
      conducted in the Integrated Primary Care Information (IPCI) general practice
      research database. Software was built to allow for automated patient
      identification and recruitment, and randomization. As an application, we compared
      gastrointestinal tolerability in persons treated with diclofenac and celecoxib
      for osteoarthritis. The outcomes were assessed in the IPCI database. To assess
      accuracy of exposure and outcome, we also collected information by self
      administrated patient questionnaires. For all eligible subjects, we assessed the
      main reason for noninclusion. Physicians were interviewed to evaluate the study
      and to identify the major obstacles. RESULTS: Forty-two general practice
      physicians collaborated with the study and 7,127 potential study subjects were
      identified. Among these subjects, 170 were eligible for recruitment and 20
      (11.8%) were randomized. Of the eligible patients, 96 (56.5%) were not recruited
      because the physician was too busy or the patient was treated by another
      healthcare provider and 54 (31.8%) were not recruited because of exclusion
      criteria. CONCLUSION: Concordance between questionnaires and IPCI data and the
      outcome was good (kappa=0.7; SD=0.14). The physicians reported that recruitment
      during routine visits was too time-consuming, in particular because of the need
      for informed consent. Although a randomized database study is feasible, patient
      recruitment during routine consultations should be avoided.

PMID- 16632139
TI  - Recall bias did not affect perceived magnitude of change in health-related
      functional status.
AB  - BACKGROUND AND OBJECTIVE: It was hypothesized that within an invasively treated
      group and within a group that improved in angina pectoris no difference in effect
      size would occur between prospective and retrospective measures. Furthermore, it
      was hypothesized that assessment of perceived change at post-test may be invalid
      because of recall bias and present-state bias. STUDY DESIGN AND SETTING: Effect
      sizes (as standardized response means) were used as indicators of magnitude of
      change. Linear structural equation analysis (with LISREL) was used to investigate
      the relationship between the estimates of recall accuracy and retrospectively
      assessed change. RESULTS: No significant differences were found between
      prospective and retrospective measures of change over time in health-related
      functional status. Recall bias was not associated with retrospective measurement
      of change within a 12-week interval. An expected present-state effect was found
      in a structural equation model. CONCLUSION: Prospective and retrospective indices
      of magnitude of change were similar between groups receiving treatment of known
      efficacy. Recall bias seems to be an acceptable risk in short-term follow-up
      studies.

PMID- 16632140
TI  - A study of the noninstrumented physical examination of the knee found high
      observer variability.
AB  - OBJECTIVE: This study estimated the inter- and intraobserver reliability of a set
      of noninstrumented physical examination measures for knee pain in older adults.
      STUDY DESIGN AND SETTING: Forty-five patients from primary care, and 13 patients
      from secondary care, were each examined by two out of a team of three physical
      therapists, and were reexamined by one of these observers 1 month later. The
      examination items were standardized and included dichotomous, ordinal and
      continuous variables considered relevant to a primary care context. RESULTS: For
      individual dichotomous items, median interobserver and intraobserver agreement
      (kappa) was 0.22 (interquartile range IQR=0.12-0.35) and 0.41 (IQR=0.28-0.56)
      respectively. For ordinally rated variables, weighted kappa ranged from -0.08 to
      0.43 for interobserver agreement, and from 0.00 to 0.79 for intraobserver
      agreement. The median intraclass correlation coefficient for continuous
      examination variables was 0.80 (range 0.68-0.89) for interobserver agreement, and
      0.84 (range 0.67-0.95) for intraobserver agreement. CONCLUSION: For trained but
      nonexpert examiners, agreement was generally poor for dichotomous and ordinal
      examination items; however, kappa-values are liable to be depressed by the low
      prevalence of clinical signs in this sample. Agreement on continuous variables
      was notably better.

PMID- 16632141
TI  - Postal surveys of physicians gave superior response rates over telephone
      interviews in a randomized trial.
AB  - BACKGROUND AND OBJECTIVES: To compare general practitioner (GP) response to a
      telephone interview with response to a postal survey with three reminders in a
      randomized controlled trial. METHODS: GPs were randomly assigned to either a
      telephone interview or a postal survey. GPs in the telephone group were mailed a
      letter of invitation and asked to undertake a telephone interview. GPs in the
      postal group were mailed a letter of invitation and questionnaire. Non-responders
      were sent up to three reminders, the final by registered post. Response rates
      were calculated for each group. RESULTS: 416 GPs were randomized to the telephone
      interview and 451 to the postal survey. Eighty-six in the telephone group and 30
      in the postal were ineligible. One hundred thirty-four GPs completed the
      telephone interview with a response rate of 40.6% (95% confidence interval [CI]:
      35.3%, 46.1%). Two hundred fifty-two GPs completed the postal survey with a
      response rate of 59.9% (95%CI: 55.0%, 64.6%). The difference in response was
      19.3% (95%CI: 12.2%, 26.3%). CONCLUSIONS: These results show that postal surveys
      with three reminders can have superior response rates compared with a telephone
      interview.

PMID- 16632142
TI  - The WOMQOL instrument measured quality of life in women of reproductive age with
      no known pathology.
AB  - BACKGROUND AND OBJECTIVES: The Women's Quality of Life Questionnaire (WOMQOL) was
      developed to measure aspects of the health of women of reproductive age with no
      known pathology. METHODS: Five experts in women's health and mental health rated
      a pool of 140 items as very significant, somewhat significant, or insignificant
      to women's health. Sixty-seven items were retained and formatted as a self
      reported questionnaire with dichotomous responses to each statement ("true" and
      "false"). A total of 1,207 women completed the instrument during the follicular
      and late luteal phases of their menstrual cycles. Dichotomous response data from
      the follicular phases were analyzed using item response theory-based full
      information item factor analysis to identify interpretable factors. Measurement
      invariance of the obtained factors across cycle phases and age cohorts was
      further evaluated using differential item functioning (DIF). RESULTS: Four
      primary factors, made up of the 10 items with highest factor loading in each
      factor, were found to measure physical, mental, social, and spiritual health. No
      items were found to display DIF across the phases of menstrual cycles or age
      cohorts. CONCLUSION: Although additional studies of diverse groups of women are
      advised, the final 40-item WOMQOL is a psychometrically sound measure that can be
      used to evaluate the quality of life of women of reproductive age in the general
      population.

PMID- 16632143
TI  - High anxiety is associated with an increased risk of death in an older tri-ethnic
      population.
AB  - BACKGROUND AND OBJECTIVES: The health consequences of anxiety in late life have
      not been adequately investigated. We sought to examine the association between
      anxiety and death in an older tri-ethnic population. METHODS: A longitudinal
      population-based study of 506 older noninstitutionalized non-Hispanic Whites, non
      Hispanic Blacks, and Hispanics aged 75 years or older from Galveston County.
      RESULTS: Average age was 80.8 (SD 4.4) and 50.8% were women. Older non-Hispanic
      Whites (21.6%) reported the highest prevalence of anxiety, followed by Hispanics
      (12.4%) and non-Hispanic blacks (11.3%) (P=.0001). High anxiety was significantly
      associated with an increased hazard of all cause death (HR 1.52; 95% CI 1.02,
      2.28) and cardiovascular death (HR 1.90; 95% CI 1.06, 3.36); and was associated
      with an increased hazard of cancer death (HR 2.38; 95% CI 0.88, 6.45) during 5
      years of follow-up. CONCLUSION: There is a high prevalence of anxiety in late
      life. Our results indicate an association between anxiety and increased risk of
      death in persons aged 75 and older.

PMID- 16632144
TI  - Dimensional structure of the SF-36 in neurological patients.

PMID- 16632145
TI  - Re: ethics committee decisions are best taken as weighted evaluations from the
      whole meeting.

PMID- 16632147
TI  - Development of a dermal cancer slope factor for benzo[a]pyrene.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are commonly found at environmentally
      impacted sites in both Canada and the United States, and also occur naturally.
      Typically, benzo[a]pyrene (B[a]P) is selected as a standard to which the cancer
      potencies of other carcinogenic PAHs are compared. Cancer potency estimates for
      B[a]P have been published for the oral and inhalation routes of exposure,
      however, no such estimate has been established by a regulatory agency for dermal
      exposure. The main objectives of the current investigation were to: evaluate
      approaches used to examine the relative carcinogenicity of PAHs; to conduct a
      review of mammalian dermal carcinogenicity studies for B[a]P; and derive a cancer
      slope factor for dermal exposure to PAHs using B[a]P as a surrogate for other
      PAHs. The toxicological database of dermal B[a]P studies was examined for
      relevant animal bioassays. Seven relevant studies were identified. A cancer slope
      factor for B[a]P was developed using the benchmark dose approach and the
      linearized multistage model. The upper 95th CI at the 5% effect level above
      background incidence was used as the point of departure for low-dose linear
      extrapolation. An average slope factor of 0.55 (microg/animal day)(-1) was
      calculated for mice, which was converted to a dose-equivalent slope factor of 25
      (mg/kg day)(-1). This latter slope factor is proposed for application to human
      health risk assessment with no scaling adjustment. Dermal potency equivalency
      factor values were identified which may be used with other carcinogenic PAH in
      the calculation of total B[a]P equivalent dermal cancer risk estimates. An
      identified area for further investigation is the consideration of scaling in
      extrapolating the calculated dermal cancer slope factor from mice to humans.

PMID- 16632148
TI  - Imaging findings of familial Mediterranean fever.
AB  - PURPOSE: The aim of this study was to study the imaging findings of familial
      Mediterranean fever (FMF). MATERIALS AND METHODS: We performed a retrospective
      review of the medical records and imaging studies of 38 patients with proven FMF,
      diagnosed between 1992 and 2002. RESULTS: The most common clinical manifestation
      was recurrent peritoneal attacks with abdominal pain (76.3%) and fever (42.1%).
      Abdominal imaging findings included ileus (n=12), splenomegaly (n=5),
      hepatomegaly (n=2), ascitis (n=2), focal peritonitis (n=2), mesenteric streaking
      (n=1), and enlarged mesenteric lymph node (n=1). One patient developed fatal
      peritoneal mesothelioma, and 13.1% of the patients developed amyloidosis with
      sonographic findings of renal parenchymal disease or cardiomyopathy. Arthritis
      was second in frequency, occurring in 34.2% of patients; radiographs were normal
      (n=4) or showed joint effusion and periarticular soft tissue swelling (n=4) due
      to synovitis. One patient developed seronegative destructive arthropathy. Skin
      lesions were noted in 23.6% of patients. Pleuritis was encountered in 13.1% and
      pericarditis in 5.2%. Polyarteritis nodosa (PAN) was present in two patients,
      multiple sclerosis in one, and autoimmune hemolytic anemia in one patient.
      CONCLUSION: FMF predominantly involves abdominal viscera but can affect other
      organs. The majority of patients have nonspecific imaging findings, and the
      radiologic diagnosis is rarely considered. Amyloidosis, mesothelioma, and
      destructive arthropathy are potential serious complications of FMF. PAN, multiple
      sclerosis, and autoimmune hemolytic anemia are probably rare associations or
      rather than coincident with FMF.

PMID- 16632149
TI  - Evaluation of the three-time-point method for diagnosis of breast lesions in
      contrast-enhanced MR mammography.
AB  - PURPOSE: To evaluate the three-time-point (3TP) method for diagnosis of breast
      lesions detected on contrast-enhanced MR mammography. MATERIALS AND METHODS: MR
      imaging was performed in 40 women with 120 suspected breast lesions in
      mammography and/or sonography. The contrast kinetics was converted by 3TP
      software on a pixel-by-pixel basis into color-coded images. Lesion diagnosis was
      made by analysis of color intensity and color hue. The 3TP results were compared
      with the results of the region-of-interest (ROI) method. In 16 patients, we were
      able to correlate the results with histopathological findings. RESULTS: The 3TP
      method could successfully be performed in all MR mammographies. Forty (33%)
      lesions had a diameter of less than 5 mm, 56 (47%) lesions between 5 and 10 mm,
      and 24 (20%) lesions were greater than 1 cm. Of all 120 lesions, 65 (54%) showed
      heterogeneous contrast enhancement. In 117 (97%) of all 120 lesions the results
      of ROI and the automated 3TP method were considered equivalent. However, in three
      lesions the manual ROI differed from the 3TP method. After a second, repeated
      manual ROI placement, we were able to confirm equivalent results with the 3TP
      images as well. CONCLUSIONS: The 3TP method automatically and reliably converts
      contrast kinetic information of the entire breast into a color-coded image. The
      3TP method presents kinetic information of the entire dynamic series in an easy
      to-interpret format and this automated method may allow to forego time-consuming
      and sometimes subjective manual ROI placements. This method displays the
      heterogeneity of the contrast enhancement pattern often observed in malignant
      lesions and makes it usable as diagnostic criterion.

PMID- 16632150
TI  - Gadolinium-enhanced pulmonary magnetic resonance angiography in the diagnosis of
      acute pulmonary embolism: a prospective study on 48 patients.
AB  - OBJECTIVE: Gadolinium-enhanced pulmonary magnetic resonance angiography (MRA) can
      be an option in patients with a history of previous adverse reaction to iodinated
      contrast material and renal insufficiency. Radiation is also avoided. The aim of
      this study is to prospectively compare the diagnostic value of MRA with that of a
      diagnostic strategy, taking into account catheter angiography, computed
      tomography angiography (CTA), and lung scintigraphy [ventilation-perfusion (VQ)].
      MATERIAL AND METHODS: Magnetic resonance angiography was done in 48 patients with
      clinically suspected pulmonary embolism (PE) using fast gradient echo coronal
      acquisition with gadolinium. Interpretation was done with native coronal images
      and multiplanar maximum intensity projection reconstructions. Results were
      compared to catheter angiography (n=15), CTA (n=34), VQ (n=45), as well as 6-12
      months clinical follow-ups, according to a sequenced reference tree. RESULTS: The
      final diagnosis of PE was retained in 11 patients (23%). There were two false
      negatives and no false positive results with MRA. Computed tomography angiography
      resulted in no false negatives or false positives. Magnetic resonance angiography
      had a sensitivity of 82% and a specificity of 100%. CONCLUSION: In our study,
      pulmonary MRA had a sensitivity of 82% and a specificity of 100% for the
      diagnosis of PE, with slightly less sensitivity than CTA. In the diagnostic
      algorithm of PE, pulmonary MRA should be considered as an alternative to CTA when
      iodine contrast injection or radiation is a significant matter.

PMID- 16632151
TI  - Volume-expanding complications after pneumonectomy: comparison of CT findings.
AB  - The purpose of this study was to assess and characterize the computed tomographic
      (CT) findings of various volume-expanding complications occurring in the
      postpneumonectomy space. Chest CT scans, obtained in 17 patients in whom plain
      chest radiographs had revealed shift of the mediastinum away from the surgical
      side after pneumonectomy for lung cancer, were retrospectively reviewed.
      Recurrent neoplasm (n=6) appeared as soft-tissue mass projecting into the
      postpneumonectomy space and/or enlarged mediastinal lymph nodes. Empyema (n=4)
      was manifested by smooth thickening of the residual pleura with or without
      thickening of the extrapleural tissues. Hemothorax (n=4) was characterized by
      amorphous material of high attenuation contained within the postpneumonectomy
      space. Chylothorax (n=2) presented no abnormal finding except for expansion of
      the postpneumonectomy space. The remaining one case showed only expansion of the
      postpneumonectomy space and it was normalized without any treatment, which was
      supposed to be transient pleural fluid collection of uncertain cause. When
      mediastinal shift away from the surgical side occurs on plain chest radiography
      following pneumonectomy, CT can be helpful in differentiating various volume
      expanding complications providing characteristic features.

PMID- 16632152
TI  - Computed tomography findings in 66 patients with malignant pleural mesothelioma
      due to environmental exposure to asbestos.
AB  - We aimed to investigate the computed tomography (CT) findings of malignant
      pleural mesothelioma (MPM) caused by environmental asbestos exposure. We
      retrospectively reviewed CT scans of 66 patients, which were performed before any
      invasive procedure was done. Pleural effusion (80.3%), pleural thickening
      (77.2%), volume contraction (37.9%), involvement of mediastinal pleura (31.8%)
      and interlobar fissure (28.8%) were the most common CT findings of MPM. Although
      none of these findings are pathognomonic for MPM, they may provide valuable clues
      for the differential diagnosis, at least in patients with a history of asbestos
      exposure.

PMID- 16632153
TI  - Frequency of coronary artery calcification on low-dose computed tomography
      screening for lung cancer.
AB  - PURPOSE: The purpose of this study was to determine the frequency of coronary
      artery calcification (CAC) in high-risk people undergoing computed tomography
      (CT) screening for lung cancer. METHODS: Between 1999 and 2004, we performed CT
      screening for lung cancer on 4250 participants, all without documented prior
      cardiovascular disease, using multidetector-row (MD) CT. Of the patients, 1102
      underwent imaging with a four-detector-row CT at 120 kVp and 40 mA, with pitch
      1.5 and collimation of 2.5 mm in a single breath hold of 15-20 seconds, and 3148
      did with an eight-detector-row CT at the same kVp, mA, and pitch settings but
      with collimation of 1.25 mm. Visualized CACs in each coronary artery (main, left
      anterior descending, circumflex, and right) were scored separately as 0 (absent),
      1 (mild), 2 (moderate), or 3 (severe), yielding a possible score of 0-12 for each
      person. Frequency distributions by gender, age, and pack-years of smoking were
      determined. Odds ratios (ORs) were calculated using logistic regression analysis
      of the prevalence of CAC as a joint function of gender, age, pack-years of
      smoking, and presence of diabetes. RESULTS: Among the subjects younger than 50
      years, positive CAC scores were three times more frequent for men than for women
      (22% vs. 7%); among those older than 50 years, the frequency increased for both
      men and women but the increase for women was greater than that for men. The
      frequency of positive CAC scores increased with increasing pack-years of smoking;
      it was always higher for men than for women. The ORs were 2.6 for male gender
      (P<.0001), 3.7 and 9.6 for ages 60-69 years and 70 years or older, respectively,
      for increasing age (P<.0001 for both), 1.6 and 2.3 for 30-59 pack-years and 60
      pack-years or longer, respectively, for increasing pack-years of smoking (P<.0001
      for both), and 1.6 for having diabetes (P=.016). CONCLUSION: The CAC score can be
      derived from ungated low-dose MDCT images. This information can contribute to
      risk stratification and management of coronary artery disease.

PMID- 16632154
TI  - Accuracy of preoperative routine MRI for hepatic lesion detection.
AB  - BACKGROUND: The outcome of liver resections depends on complete removal of all
      detectable foci. Our aim was to determine the value of preoperative routine
      magnetic resonance imaging (MRI) for complete detection of hepatic lesions.
      METHODS: We compared 271 lesions seen on MRI in 182 patients to intraoperative
      findings (including intraoperative ultrasonography) and histology. RESULTS: The
      overall rate of lesions was 7% each for segments 2 and 3, as compared to 14-17%
      each for segments 5, 6, 7, and 8. Twenty-three additional lesions were found
      intraoperatively, two thirds of them in the left lobe (mean size: 1.4 cm; mean
      total number of lesions in those patients: 2.2). In segments 2 and 3, the
      relative frequency for intraoperative diagnosis of additional lesions was 17% and
      20%, respectively. On the other hand, most of the 15 MRI lesions not verified
      intra- or postoperatively had been described in the right hepatic lobe (maximum:
      segment 6). CONCLUSION: MRI provided reliable preoperative lesion detection.
      Special attention should be paid to segments 2 and 3, which showed a lower total
      number of lesions but an elevated relative frequency of intraoperatively detected
      additional foci.

PMID- 16632155
TI  - Magnetic resonance cholangiography features of biliary abnormalities due to
      cavernous transformation of the portal vein.
AB  - BACKGROUND: The aim of this retrospective and monocentric study was to describe
      the magnetic resonance cholangiography (MRC) features of biliary abnormalities
      related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From
      September 2001 to May 2003, MRC was performed in 10 consecutive patients who had
      a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC
      in nine patients. It consisted of stenoses, ductal narrowing or irregularities
      involving the common bile duct for three patients with extrahepatic portal vein
      thrombosis discovered a mean of 1.5 years ago, or involving both right and left
      intrahepatic bile ducts and common bile duct for six patients with extrahepatic
      portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of
      intrahepatic bile ducts was seen for seven patients, four of them having
      cholestasis. For three patients with symptomatic cholestasis, direct
      cholangiography (DC) was performed and showed the same findings as MRC which
      nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC
      seems to constitute an accurate tool to investigate noninvasively patients with
      portal biliopathy.

PMID- 16632156
TI  - Magnetic resonance venography of achondroplasia: correlation of venous narrowing
      at the jugular foramen with hydrocephalus.
AB  - In achondroplasia, venous narrowing associated with a small skull base leads to
      elevated venous pressure which impairs cerebrospinal fluid (CSF) absorption,
      resulting in communicating hydrocephalus. We correlated venous narrowing at the
      jugular foramina and collateral circulation on magnetic resonance venography
      (MRV) with ventricular size in 17 patients. Patients were divided into three
      groups: Group I: progressive hydrocephalus; Group II: nonprogressive
      hydrocephalus; and Group III: normal ventricular size. The grades of venous
      narrowing and types of collaterals were well correlated with hydrocephalus
      groups.

PMID- 16632157
TI  - Peripheral neurogenic tumors: is the use of different types of imaging
      diagnostically useful?
AB  - We report a series of six benign peripheral neurogenic tumors (five schwannomas
      and one neurofibroma) studied by 3D ultrasonography (US) and magnetic resonance
      imaging (MRI). The findings demonstrated by US and MRI are variable, but usually
      permit the diagnosis of benign nervous tumor without prejudging the final
      histological diagnosis. MRI does not bring forward further complementary images
      to those observed at US, which is limited by its dependence on its operator. The
      use of 3D US will be sufficient for the diagnosis and preoperative evaluation of
      a lesion when it is possible to furnish the volumetric data and the tools
      necessary for data analysis in a single document (in a CD).

PMID- 16632158
TI  - Radiology-pathology conference: osteosarcoma in a cartilaginous exostosis of the
      femur.
AB  - Osteochondromas are common lesions in the metaphyseal segments of the long bones
      and are known to be able to degenerate into chondrosarcoma. We present the case
      of a 20-year-old patient with an osteosarcoma at the base of a cartilaginous
      exostosis and discuss the causal relationship between the two lesions on the
      basis of the radiologic and pathologic findings.

PMID- 16632159
TI  - Recanalization and reversal of diffusion abnormalities and markedly reduced
      cerebral blood volume in a patient with transient ischemic attack.
AB  - Resolution of diffusion abnormalities is a finding that is rarely seen in
      hyperacute cerebral ischemia. We report a serial study of diffusion and perfusion
      magnetic resonance imaging (MRI) in a case of transient ischemic attack (TIA). In
      the current case, marked decrease of cerebral blood volume (CBV) as well as
      reduced diffusion in the affected middle cerebral arterial territory was shown by
      the initial diffusion and perfusion MRI at 1.5 h after onset. The initial MRI
      findings as well as neurological symptoms recovered probably due to prompt and
      spontaneous recanalization of thrombosed vessel.

PMID- 16632160
TI  - Brucellar spondylodiscitis: noncontiguous multifocal involvement of the cervical,
      thoracic, and lumbar spine.
AB  - Brucellosis is a zoonosis of worldwide distribution presenting with a wide
      clinical spectrum. Brucellosis can involve any organ or system. The axial
      skeleton is the most common site of involvement with a frequency ranging from 2%
      to 53%. Multiple-level spinal involvements are rare. This report describes the
      first case of noncontiguous synchronous multifocal involvement of all cervical,
      thoracic, and lumbar regions in a patient with brucellar spondylodiscitis.

PMID- 16632161
TI  - Imaging findings of retroperitoneal lymphangiomyomatosis in a patient with
      lymphoma.
AB  - A 31-year-old female with lymphoma was incidentally found to have a left
      retroperitoneal lymphangiomyomatosis (LAM). The tumor was proved by pathology and
      immunohistochemical study of the tissue specimen obtained by ultrasound-guided
      core needle biopsy. The characteristic sonographic, computed tomographic,
      magnetic resonance imaging, and positron emission tomographic (PET) features of
      this unusual lesion were described. It was managed conservatively and remained
      stable on 2-year follow-up study. LAM should be considered in the differential
      diagnoses in cases of a retroperitoneal solid mass with cystic components.

PMID- 16632162
TI  - Severe liver enzyme elevations after three years of olanzapine treatment: a case
      report and review of olanzapine associated hepatotoxicity.
AB  - Atypical antipsychotics commonly cause isolated asymptomatic increase in the
      aminotransferase levels. Among these atypical antipsychotics, mostly transient,
      asymptomatic increase in hepatic enzymes has been reported with olanzapine,
      however olanzapine rarely may induce a clinical and/or biological hepatic
      toxicity. The pathogenesis of olanzapine-associated hepatotoxicity is not well
      known and is mostly a transient phenomenon. However, substantial and lasting
      changes may occur and result in symptomatic hepatitis. In the following case
      report, we report on a 44-year-old female patient diagnosed as Bipolar Disorder
      Type I, whose liver enzyme levels increased ten fold of normal ranges during the
      third year of the olanzapine treatment and returned to the normal levels within
      three weeks after olanzapine discontinuation. Although significant liver enzyme
      elevations are uncommon during olanzapine treatment, based on reports of serious
      hepatotoxicity, controlled and longitudinal research are needed to learn side
      effects of this drug on liver. Clinicians should be aware of possible hepatotoxic
      effects of atypical antipsychotics and should monitor the liver enzyme levels
      whenever they feel necessary.

PMID- 16632163
TI  - Low-dose mirtazapine may be successful treatment option for severe nausea and
      vomiting.
AB  - The antagonism of 5-HT3 receptor by mirtazapine results in an antiemetic effect,
      suggesting that mirtazapine could be considered a successful antiemetic agent in
      patients suffering from severe nausea and vomiting. There have been several
      reports of successful mirtazapine treatment for nausea or vomiting from secondary
      causes but cases of primary severe nausea and vomiting are still lacking, in
      particular, there are no reported cases in Asians. The authors report two cases
      with severe nausea and vomiting that were dramatically treated with mirtazapine
      in the Korean population.

PMID- 16632164
TI  - [Abdominoplasty after twin pregnancy: study of 30 cases].
AB  - INTRODUCTION: Compared to single mother-hood, the twin pregnancy results in
      important esthetic and functional sequelae of the abdominal wall. The
      considerable uterine growth involves a musculocutaneous diastasis of both the
      supra-umbilical and the infra-umbilical area. This study presents the modified
      abdominoplasty technique with an inverted T scar as the appropriate treatment of
      supra-umbilical and infra-umbilical musculocutaneous defects. METHODS AND
      MATERIALS: This series reviews a total of 30 female patients of 35 years on
      average. There was no cases obesity or smoking reported. Surgical treatment
      consisted in a skin and fat resection following an inverted T scar design and
      associated to a muscle plication. In 6 patients it has been necessary to repeat
      the procedure in 6 months time. RESULTS: All 30 patients resolved with an
      aesthetic and functional improvement. No instances of abdominal diastasis
      recidivation occurred. There were no complication observed and no impact on the
      healing process was referred. CONCLUSION: on of the main differences between
      single and twin pregnancies is that the second ones are concerned by an abdominal
      diastasis marked on both a vertical and a transversal direction. The complete
      surgical treatment sometimes includes a second intervention. Clinical results and
      luck of complications suggest that the T-type abdominoplasty associated to a
      muscle re-tightening offers an appropriate surgical treatment of patients
      concerned.

PMID- 16632165
TI  - The D2 dopamine receptor (DRD2) gene is associated with co-morbid depression,
      anxiety and social dysfunction in untreated veterans with post-traumatic stress
      disorder.
AB  - OBJECTIVE: To identify clusters of patients with post-traumatic stress disorder
      (PTSD) according to symptom profile and to examine the association of the A1
      allele of the D2 dopamine receptor (DRD2) gene with these clusters. METHOD: Fifty
      seven untreated Caucasian Vietnam veterans with PTSD were administered the
      General Health Questionnaire-28 (GHQ) and the Mississippi Scale for combat
      related PTSD. DRD2 allelic status was determined by PCR. RESULTS: Subjects with
      the DRD2 Al allele compared to those without this allele had significantly higher
      scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4
      (depression). Cluster analysis of the GHQ data identified two primary groups. A
      high psychopathology cluster (cluster 3), featured by high co-morbid levels of
      somatic concerns, anxiety/insomnia, social dysfunction and depression, and a low
      psychopathology cluster (cluster 1), manifested by the reverse pattern. Scores in
      each of the four GHQ groups were significantly higher in cluster 3 than cluster
      1, as was Mississippi Scale PTSD score. DRD2 A1 allele veterans compared to those
      without this allele were significantly more likely to be found in the high than
      the low psychopathology cluster group. CONCLUSIONS: DRD2 variants are associated
      with severe co-morbid psychopathology in PTSD subjects.

PMID- 16632166
TI  - Illness behaviour in neurological inpatients with psychiatric morbidity.
AB  - OBJECTIVE: The aim of the present study was to examine whether psychiatric
      morbidity can influence the type of illness behaviour of neurological inpatients.
      METHODS: For this purpose, we compared neurological inpatients with and without
      psychiatric disorders (DSM-IIIR criteria) for the seven scales of Illness
      Behaviour Questionnaire (IBQ) and searched for possible differences between the
      two patient subgroups. RESULTS: Of the 105 neurological inpatients who
      participated in the study, 54 (51.4%) were diagnosed as having some type of
      psychiatric disorder. These patients scored significantly higher than patients
      without psychiatric morbidity in the scale of Irritability. A suggestive trend
      for higher scores in the scales of Hypochondriasis, Disease Conviction, and
      Affective Disturbance, and significantly lower score in the scale of Denial, in
      patients with psychiatric morbidity, were also found. CONCLUSION: The present
      study has shown that neurological inpatients with psychiatric morbidity tend to
      develop more intense illness behaviour than those without. The effect of
      psychiatric morbidity on certain components of illness behaviour in neurological
      patients can be taken into account when therapeutic strategies are planned.

PMID- 16632167
TI  - Cognitive impairment in patients with chronic hepatitis treated with interferon
      alpha (IFNalpha): results from a prospective study.
AB  - BACKGROUND: Treatment with low-dose interferon alpha (IFN-alpha) is often
      associated with neuropsychiatric side effects. In addition to depression and
      anxiety, IFN-alpha associated cognitive impairment significantly affects
      patient's mental health and quality of life. AIMS OF THE STUDY: To measure
      possible effects of low-dose IFN-alpha on cognitive functioning and its
      relationship to the development of depression and anxiety. METHOD: We
      prospectively followed 38 patients with a chronic hepatitis B or C by
      neuropsychological tests and psychiatric self-rating scales during 12 weeks of
      low-dose treatment with IFN-alpha. RESULTS: Before IFN-alpha treatment,
      neuropsychological tests as well as self-ratings in the Beck's Depression
      Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS) and the Self
      Report Symptom Inventory 90 Items-Revised (SCL-90-R) were within the normal
      range. Following 12 weeks of treatment with IFN-alpha resulted in a slight, but
      significant increase in depression scores. Neuropsychological assessment after 12
      weeks of IFN-alpha treatment showed a significant decrease of the immediate
      recall in the Auditory-Verbal Learning Test (AVLT) and a significant reduction of
      words recited in the Controlled Oral Word Association Test (COWA). Cognitive
      impairment did not significantly correlate with depressive symptoms or anxiety.
      CONCLUSION: Our results indicate that even low-dose IFN-alpha induces cognitive
      impairment independent from depressive symptoms, which might be related to
      functional disturbances in the prefrontal cortex and the hippocampus. We suggest
      close monitoring of cognitive function during IFN-alpha treatment of chronic
      hepatitis.

PMID- 16632168
TI  - The academic lineage of Sir John Carew Eccles (1903-1997).
AB  - This report reviews the academic lineage of Sir John Eccles; who trained him,
      whom he then trained and with whom he collaborated, and the subsequent impact of
      his trainees and collaborators on neuroscience and other areas. In a post
      training career at five institutions in four countries (Great Britain, Australia,
      New Zealand, back to Australia, USA) and during retirement in Switzerland, Eccles
      trained and collaborated with over 180 people (mostly neuroscientists) from 21
      countries. Most of them have had stellar research and training records that span
      the cellular-behavioral-philosophical spectrum of neuroscience, with a focus from
      peripheral neuromuscular issues to the forebrain. Some have been equally
      distinguished in other areas of biomedical science. Eccles' academic
      contributions and lineage are a valuable colloquium topic in a neuroscience
      training program. His experimental work spanned much of the 20th C before the
      recent emphasis on the application of the techniques of molecular biology. He
      continually sought to integrate information from the cellular to the systems and
      behavioral levels of analysis and synthesis. He also devoted a substantial amount
      of his intellectual effort to the mind-brain and other philosophical issues.
      Eccles' prodigious working hours and enthusiasm for his projects were a role
      model for such trainees. Hard-working trainees often ask how can they retain
      their all-round interests, and indeed their humanity and citizenry, as they focus
      more and more on their necessarily narrowly focused neuroscience research. Again,
      Eccles' writings and overall behavior show that it can indeed be done, but only
      by the application of extraordinary effort and dedication.

PMID- 16632169
TI  - An analysis of the implementation of an environmental management system in a
      local public administration.
AB  - The Environmental Management System (EMS) is commonly implemented in private
      firms. However, on the basis of a strengths, weaknesses, opportunities and
      threats (SWOT) analysis, our work analyzes the consequences of implementing an
      EMS within the context of local public administrations, particularly regarding
      the City Council of Ohanes in Almeria (Spain). This is the first European
      corporation to implement an EMS according to the ISO 14001 Standard, certified by
      the Spanish Association of Normalization and Certification. Its analysis would be
      equivalent to the Shumpeterian "market innovator study", so that public
      administration "followers" can take advantage of the derived benefits and of
      minimizing the negative effects of such an experience. On the other hand, we show
      that the economic and environmental advantages derived from the EMS go beyond the
      activities that the City Council is in charge of. They have spillover effects
      that extend them to all economic activities in the municipality and these effects
      are expected to be increased in the medium and long-term perspective. In this
      paper, we compare the costs and benefits that the municipality obtains in two
      cases: the City Council implements the EMS or it does not implement it. The main
      objective of this article is to show the economic and environmental advantages
      obtained by a municipality when it is only the City Council who is implementing
      an EMS. It is logical to suppose that this case study can stimulate other
      municipalities to use this instrument, even if the economic and environmental
      characteristics of the municipality are different.

PMID- 16632171
TI  - Zinc requirements and the risks and benefits of zinc supplementation.
AB  - The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily.
      On this basis and based on estimates of bioavailability of zinc, dietary
      recommendations are made for apparently healthy individuals. Absent chemical,
      functional, and/or physical signs of zinc deficiency are assumed indicative of
      adequacy. More specific data are seldom available. Changing food preferences and
      availability, and new food preparation, preservation, and processing technologies
      may require re-evaluation of past data. Conservative estimates suggest that 25%
      of the world's population is at risk of zinc deficiency. Most of the affected are
      poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting
      on foods that are rich in inhibitors of zinc absorption and/or contain relatively
      small amounts of bioavailable zinc. In contrast, among the relatively affluent,
      food choice is a major factor affecting risk of zinc deficiency. An additional
      problem, especially among the relatively affluent, is risk of chronic zinc
      toxicity caused by excessive consumption of zinc supplements. High intakes of
      zinc relative to copper can cause copper deficiency. A major challenge that has
      not been resolved for maximum health benefit is the proximity of the recommended
      dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc.
      Present recommendations do not consider the numerous dietary factors that
      influence the bioavailability of zinc and copper, and the likelihood of toxicity
      from zinc supplements. Thus the current assumed range between safe and unsafe
      intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is
      complex, involving a number of chemical and functional measurements that have
      limitations in sensitivity and specificity. This approach needs to be enhanced so
      that zinc deficiency or excess can be detected early. An increasing number of
      associations between diseases and zinc status and apparently normal states of
      health, where additional zinc might be efficacious to prevent certain conditions,
      point at the pharmacology of zinc compounds as a promising area. For example,
      relationships between zinc and diabetes mellitus are an area where research might
      prove fruitful. In our opinion, a multidisciplinary approach will most likely
      result in success in this fertile area for translational research.

PMID- 16632172
TI  - Serum molybdenum concentration in healthy Japanese adults determined by
      inductively coupled plasma-mass spectrometry.
AB  - The serum molybdenum (Mo) concentrations in 70 Japanese adults (35 males and 35
      females) not receiving any medical care or treatment were determined by
      inductively coupled plasma-mass spectrometry. Serum Mo concentration in the
      subjects ranged from <0.1 to 9.11 ng/mL. More than half (55.7%) of the subjects
      showed values of less than 1 ng/mL and only 6 (8.6%) subjects showed more than 2
      ng/mL. The mean+/-SD, geometrical mean (GM), range of GM+/-geometrical SD (GSD)
      and median value were 1.21+/-1.34, 0.81, 0.30 to 2.16, and 0.90 ng/mL,
      respectively. Among age, body mass index and several serum biochemical values,
      activities of aspartate aminotransferase and alanine aminotransferase showed
      significant associations with serum Mo; 15 subjects suspected of having liver
      dysfunction showed significantly higher serum Mo than others. We propose a range
      of 0.10-4.73 ng/mL, estimated as a range of GM+/-2GSD of serum Mo in the
      remaining 55 subjects without liver dysfunction, as a reference range of serum Mo
      in Japanese healthy adults.

PMID- 16632173
TI  - The release of metals from metal-on-metal surface arthroplasty of the hip.
AB  - The aim of the study was to evaluate the serum and urine levels of cobalt (Co),
      chromium (Cr), manganese (Mn), molybdenum (Mo) and nickel (Ni) in patients who
      had undergone metal-on-metal hybrid surface arthroplasties on the supposition
      that a release of metals would occur due to the large head size of this type of
      implant. Metal levels were determined by using an analytical method based on
      sector field inductively coupled plasma mass spectrometry. Results showed a
      significant difference between patients and control subjects in mean levels of Co
      and Cr in serum (p<0.0001 and p=0.02, respectively) and in urine (p<0.0001 for
      both). No significant differences were observed in mean serum and urinary levels
      of Mn, Mo and Ni. Although the clinical consequences of these changes, if any,
      are unknown, further studies could be performed in a larger number of subjects
      implanted with a total surface arthroplasty at follow-up times over different
      periods.

PMID- 16632174
TI  - Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin
      deficient rats.
AB  - Two sources of chromium III, "chromium 454" and "chromium picolinate," were
      tested in insulin-deficient Streptozocin-treated diabetic rats. This model was
      selected in order to evaluate the possibility of any hypoglycemic potency of
      chromium in a relative absence of blood insulin concentration. Three weeks of the
      treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood
      glucose levels, respectively. Body weight gains were equally improved by both
      treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454
      and CrP. These results might suggest that any hypoglycemic effect of trivalent
      chromium under insulin-deficient conditions could be largely dependent upon the
      type of chromium agent and associated characteristics such as solubility and
      bioavalibility. In contrast, improvement of body weight gains and blood levels of
      CK, AST and ALT seems to be less dependent on the type of chromium compound under
      these experimental conditions. In conclusion, CRC454 showed significant reduction
      of hyperglycemia under insulin-deficient conditions.

PMID- 16632175
TI  - Influence of maternal dietary calcium levels on milk zinc, calcium and phosphorus
      contents and milk production in rats.
AB  - The aim of this study was to analyze zinc (Zn), calcium (Ca) and phosphorus (P)
      contents in milk and the lactational performance in rats fed different Ca levels.
      Female Wistar rats were fed during pregnancy and lactation with experimental
      diets containing 20% protein and high (0.90%, HCa), normal (0.60%, NCa) or low
      (0.20%, LCa) Ca levels. Milk samples were collected after 15 days to determine
      the milk mineral composition. Pup weight was recorded from birth to weaning
      (litter size: 6-8 pups) to determine weight gain and calculate milk production.
      At delivery there were no significant differences in the body weight of the pups
      between the groups, but at day 15, the LCa group showed lower values than both
      NCa and HCa groups (p<0.05). The weight gain of the LCa group was significantly
      lower than of the HCa and NCa groups, between delivery and day 5 (p<0.05). This
      reduced rate of weight gain led to the LCa group reaching weaning weight later
      than the other groups. Milk production (g/pup/day) was significantly lower when
      dams were fed the LCa than the NCa and HCa diets (p<0.05). There were no
      significant differences among the groups in milk Ca, P and Zn levels and Ca/P
      ratio. The body mineral composition of the pups at birth did not differ between
      the groups; at weaning, however, both LCa and HCa groups had lower element
      contents than the NCa group (p<0.05). In conclusion, dams fed with a diet
      containing low Ca levels produced smaller volumes of milk and their pups reached
      weaning weights later than the other groups. As the milk mineral composition was
      not affected, it can be hypothesized that in dams fed low dietary Ca, the smaller
      milk yield might have been a way of maintaining milk quality. High Ca levels
      affected neither pregnancy outcome nor lactational performance.

PMID- 16632176
TI  - Absorption of zinc and retention of calcium: dose-dependent inhibition by
      phytate.
AB  - The dose-dependent inhibitory effect of sodium phytate (myo-inositol
      hexaphosphate) on absorption of zinc and retention of calcium was studied in man.
      No systematic study of this dose-response effect has been reported to this time.
      Forty subjects were served meals containing white wheat rolls without/with
      additions of phytate. Ten subjects were given test meals containing one or two of
      the studied levels of phytate and in addition all subjects were served meals to
      which no phytate was added. The zinc content was 3.1 mg (47 micromol) and the
      calcium content 266 mg (6.6 mmol). The rolls were labelled extrinsically with
      radioisotopes, 65Zn and 47Ca, and whole-body retention of both minerals was
      measured. Totally 105 meals were served, 36 meals in which no phytate was added
      and 9-10 meals on each level of phytate. The zinc absorption in meals to which
      either 0, 25, 50, 75, 100, 140, 175 or 250 mg of phytate-P (0, 134, 269, 403,
      538, 753, 941 or 1344 micromol phytate) had been added was 22%, 16%, 14%, 11%,
      7%, 7%, 7% and 6%, respectively (mean values). The addition of 50 mg phytate-P or
      more significantly decreased zinc absorption (p=0.01) as compared to absorption
      from the test meals with no added phytate. The calcium retention at day 7 in the
      same meals was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11% (mean values). The
      addition of 100 mg phytate-P or more significantly decreased calcium retention
      (p=0.03) compared to the test meals with no added phytate. It was concluded that
      the inhibitory effect of phytate on the absorption of zinc and the retention of
      calcium was dose dependent.

PMID- 16632177
TI  - Dietary reference intakes for trace elements revisited.

PMID- 16632178
TI  - Focal S100A4 protein expression is an independent predictor of development of
      metastatic disease in cystectomized bladder cancer patients.
AB  - OBJECTIVE: The prognosis of patients with apparently localized, operable, muscle
      invasive bladder cancer depends to a large extent on the presence or absence of
      subclinical, microscopic distant metastases at the time of surgery. Expression of
      the S100A4 protein has been shown to correlate with the risk of metastasis in
      both animal tumour-model systems and clinical investigations in other tumour
      types. The purpose of the present study was to investigate the prognostic
      potential of S100A4 protein expression for predicting distant metastatic relapse
      in muscle-invasive bladder cancer. METHODS: We analyzed 108 consecutive patients,
      treated for transitional cell bladder cancer with preoperative radiotherapy and
      cystectomy. Pretherapeutic biopsies of the bladder tumours were investigated for
      immunohistochemical expression of S100A4 protein and results, along with clinical
      and histopathological data, compared with the pattern of relapses over a 10+ yr
      follow-up period. RESULTS: Focal S100A4 protein expression emerged as the only
      significant independent predictor of distant metastatic relapse and distant
      metastasis-free survival in multivariate analysis. CONCLUSION: There is a
      potential role for this marker in denoting patients with high or low risk of
      distant relapse independent of clinical stage and grade.

PMID- 16632179
TI  - Current role of lasers in the treatment of benign prostatic hyperplasia (BPH).
AB  - OBJECTIVE: Evaluate the current role of lasers in the treatment of benign
      prostatic hyperplasia (BPH). METHODS: The results of a MEDLINE search for
      randomised trials and case series of the last 5 yr and published review articles
      were analysed for the safety and efficacy of neodymium:yttrium aluminum garnet
      (Nd:YAG), potassium-titanyl-phosphate (KTP), and holmium (Ho):YAG laser
      prostatectomy. The analysis includes 12 reports on randomised clinical trials, 2
      comparative studies, 10 review articles, and a total of >5000 patients. RESULTS:
      Laser treatment of BPH has evolved from coagulation to enucleation. Blood loss is
      significantly reduced compared with transurethral resection and open
      prostatectomy. Visual laser ablation of the prostate and interstitial laser
      coagulation cause coagulative necrosis with secondary ablation. Long
      postoperative catheterisation, unpredictable outcomes, and high reoperation rates
      have restricted the use of these techniques. Ablative/vaporising techniques have
      become popular again with the marketing of new high-powered 80-W KTP and 100-W Ho
      lasers. Vaporisation immediately removes obstructing tissue. Short-term results
      are promising, but large series, long-term results, and randomised trials are
      lacking. Holmium laser enucleation (HoLEP) allows whole lobes of the prostate to
      be removed, mimicking the action of the index finger in open prostatectomy.
      Prostates of all sizes can be operated on. It is at least as safe and effective
      as transurethral resection of the prostate and open prostatectomy, with
      significantly lower morbidity. It is the only laser procedure that provides a
      specimen for histologic evaluation. CONCLUSIONS: HoLEP appears to be a size
      independent new "gold standard" in the surgical treatment of BPH.

PMID- 16632180
TI  - High surgical volume, high quality, and low costs: a perfect combination. Is it
      always possible in patients who need radical prostatectomy?

PMID- 16632181
TI  - Early experience of a living donor kidney transplant program.
AB  - OBJECTIVES: Laparoscopic nephrectomy has been shown to reduce the morbidity of
      live donor nephrectomy, but post-transplant kidney function and safety issues
      with the procedure are still of some concern. The review of our early experience
      could detect errors that should be avoided in the refining of the technique.
      METHODS: Our first sixty consecutive laparoscopic donor nephrectomies were
      analyzed retrospectively. RESULTS: There were conversions to open surgery (5%),
      all three in the first 18 cases. All donors were alive at 1 year with a
      glomerular filtration rate of 85+/-21 ml/min (78% of the basal). Patient and
      graft survival at 1 year was 100% and 95%, respectively. Creatinine nadir was
      achieved on post-transplant day 3 (creatinine, 176+/-122 micromol/l). Late renal
      function proved a continuous improvement until the 2-year follow-up (creatinine,
      135+/-29 micromol/l). Renal function recovery was better in both recipient and
      donor when the donor was < or =50 years old, compared with older patients.
      Transplant complications that required reintervention included one ureteral
      fistula, one ureteral stenosis and one case of low renal flow that was re
      vascularised. CONCLUSIONS: Technical surgical aspects such the use of Haemoloc
      clips in the clipping of the artery, the hand-assisted extraction of the kidney,
      a refined surgical technique during the transplant and avoidance of prolonged
      warm and cold ischemia, taken together with an adequate intraoperative
      hemodynamic management of the donor aid in avoiding life-threatening
      complications and achieving a good post-transplant renal function recovery.

PMID- 16632182
TI  - Efficacy of ablative high-dose-per-fraction radiation for implanted human renal
      cell cancer in a nude mouse model.
AB  - OBJECTIVES: Stereotactic body radiation therapy (SBRT) is a new therapeutic
      paradigm that uses a very large dose per fraction treatments (ablative
      hypofractionation). We investigated the use of ablative hypofractionation in
      treating human renal cell carcinoma using a nude mouse model. METHODS: Nude mice
      were injected subcutaneously with A498 human renal carcinoma cells. Tumour
      bearing animals were radiated with three fractions (one per week) for a total
      dose of 48 Gy (n = 12), while untreated animals served as controls (n = 7). The
      mice were weighed, and tumour volumes were measured at baseline and weekly until
      7 weeks post-treatment. RESULTS: Control animals demonstrated progressive tumour
      growth and were sacrificed because of either tumour size or ulceration. Tumours
      in the treatment group grew to three times their initial size over the 3 weeks of
      treatment but subsequently decreased progressively to less than 30% of their
      initial volume. All treated tumours exhibited marked cytologic changes. Tumours
      from mice sacrificed before post-treatment week 4 had a mitotic count of 1-4/10
      hpf. Tumours from mice sacrificed more than 4 weeks post-treatment (n = 4)
      demonstrated no mitoses. CONCLUSIONS: Treatment with high-dose-per-fraction
      radiation to 48 Gy resulted in a sustained decrease in tumour volume and marked
      cytologic changes. These results are preliminary--but promising--and encourage
      further research into this application of ablative hypofractionated radiation for
      kidney cancer.

PMID- 16632184
TI  - Should bladder biopsies be performed routinely after bacillus Calmette-Guerin
      treatment for high-risk superficial transitional cell cancer of the bladder?
AB  - OBJECTIVE: After endoscopic resection of high-grade superficial urothelial
      neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guerin (BCG) therapy is
      performed routinely to avoid recurrence and/or progression. Vesical biopsies
      often are performed to assess the efficacy of treatment. The aim of our study was
      to evaluate the usefulness of these biopsies. MATERIALS AND METHODS: During this
      retrospective bi-centre study, 130 patients who had undergone vesical high-grade
      tumour resection were included. There were 40 Ta associated with Tis in three
      cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG
      treatment, the following parameters were studied: cytoscopic findings, urine
      cytology and the histologic results of systematised biopsies. RESULTS: Urine
      cytology was positive (high-grade) for 26 patients and negative (normal or low
      grade) for 104 patients. For the 26 patients with positive cytology, vesical
      flexible cystoscopy findings were considered suspicious in 18 patients and normal
      in eight patients. As for the 104 patients who presented negative cytology,
      cystoscopic findings were considered negative in 76 patients and suspicious in 28
      patients. In the present study, the sensitivity of cytology and cystoscopy in the
      detection of recurrence after BCG treatment was 56% and 87.5%, respectively;
      specificity was 56% and 81.6%, respectively. When the two examinations were
      combined, sensitivity was 100%, and specificity was 76%. CONCLUSIONS: After BCG
      therapy, the association of negative flexible cystoscopy findings and normal
      urine cytology made it possible to avoid routine biopsies. Patients could
      therefore avoid the morbidity of this procedure.

PMID- 16632185
TI  - Ureteral complications in the renal transplant recipient after laparoscopic
      living donor nephrectomy.
AB  - OBJECTIVES: We report on ureteral and surgical complications in our first 110
      consecutive recipients of kidneys procured with laparoscopic living donor
      nephrectomy (LLDN). METHODS: The records of all living donor transplants with
      LLDN performed between February 1999 and December 2004, including 10 pediatric
      transplants, were reviewed retrospectively. Three urologists performed LLDN using
      a pure laparoscopic non-hand-assisted transperitoneal technique. Kidney
      transplantation was performed in a standard fashion. For ureteroneocystostomy,
      the intravesical Politano-Leadbetter (P-L) technique was used. RESULTS: Two-year
      patient and graft survival was 99% and 98%, respectively. Serum creatinine at 12
      months was 1.36+/-0.1mg/dl in adult and 0.99+/-0.23 mg/dl in pediatric
      recipients. Nineteen right donor kidneys were transplanted into adult recipients.
      Surgical complications included three symptomatic lymphoceles, one peritransplant
      haematoma and one kinking of a lower pole artery. All five (4.5%) ureteral
      complications occurred in adult recipients with a mean age of 33.2+/-2.8 years.
      The incidence of ureteral complications was not clustered around the early phase
      of our LLDN experience. Of the three (2.7%) patients diagnosed with ureteral
      obstruction, two required ureteral reimplantation, and one was managed
      conservatively. Another two patients (1.8%) with a urinary leak received a double
      J stent and a cystostomy catheter for 3 and 5 months, respectively. Of the five
      patients with a ureteral complication, three had received a donor kidney with
      more than one renal artery. CONCLUSIONS: LLDN combined with the intravesical (P
      L) ureteral implantation technique provides excellent graft outcomes with low
      recipient morbidity. Renal artery multiplicity may increase the risk of ureteral
      complications.

PMID- 16632186
TI  - Giant lithiasis in a female urethral diverticulum.
AB  - The formation of gallstones in a urethral diverticulum is a rare clinical entity
      and is usually seen in males. The case of a 50 year old woman is presented, who
      consults for hard vaginal mass and dispareunia associated with repeated urinary
      infections, with radiological images and an interesting photoendoscopic vision of
      the upper dome of the gallstone. The diverticulum was approached via vaginal way
      and the local extraction was successful.

PMID- 16632187
TI  - Is pelvic lymph node dissection necessary in patients with a serum PSA<10ng/ml
      undergoing radical prostatectomy for prostate cancer?
AB  - OBJECTIVE: Controversy persists concerning the role of pelvic lymph node
      dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing
      treatment for prostate cancer with a curative intent. The aim of this study was
      to determine the incidence of lymph node metastasis in this subgroup of patients.
      METHODS: Patients with clinically localized prostate cancer and a serum
      PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging
      examinations who underwent radical retropubic prostatectomy with bilateral
      extended PLND and with >/=10 lymph nodes detected by the pathologist in the
      surgical specimen, were included in the study. RESULTS: A total of 231 patients
      with a median serum PSA of 6.7ng/ml (range 0.4-9.98) and a median age of 62 years
      (range 44-76) were evaluated. A median of 20 (range 10-72) nodes were removed per
      patient. Positive nodes were found in 26 of 231 patients (11%), the majority of
      which (81%) had a Gleason score >/=7 in the surgical specimen. Of the patients
      with a Gleason score >/=7 in the prostatectomy specimen 25% had positive nodes,
      whereas only 3% with a Gleason score </=6 were node positive. CONCLUSIONS: The
      incidence of positive nodes in patients with clinically localized prostate
      cancer, a serum PSA<10ng/ml and a Gleason score >/=7 in the prostatectomy
      specimen was 25% after extended PLND. It seems that in this patient group
      extended PLND, including removal of nodes along the internal iliac vessels, is
      warranted.

PMID- 16632188
TI  - A correlation of FTIR spectra derived from prostate cancer biopsies with gleason
      grade and tumour stage.
AB  - OBJECTIVES: We introduce biochemistry as a second dimension to Gleason grading,
      using Fourier transform infrared (FTIR) microspectroscopy. For the first time, we
      correlate FTIR spectra derived from prostate cancer (pCA) tissue with Gleason
      score and the clinical stage of the tumour at time of biopsy. METHODS: Serial
      sections from paraffin-embedded pCA tissue were collected. One was stained with
      hematoxylin and eosin and Gleason scored; FTIR spectra were collected from
      malignant locations using a second unstained section. FTIR spectra, representing
      different Gleason grades, were used to construct a diagnostic classifier for pCA
      using linear discriminant analysis (LDA). This model was blind tested using 383
      IR spectra from 36 biopsies. RESULTS: Using a three-band Gleason criteria, we
      obtained sensitivity of > or =70% for the FTIR-LDA model to predict Gleason
      <7,=7, and >7, with specificities of > or =81%. Using a threshold of Gleason/FTIR
      LDA score of > or =8, we obtained a sensitivity and specificity of 71% and 67%,
      respectively, for the correlation with metastatic tumours using the FTIR-LDA
      system and 85% and 63%, respectively, for the correlation of metastatic tumours
      using the Gleason system. CONCLUSIONS: There is a correlation between tissue
      architecture using Gleason score with tissue biochemistry using FTIR-LDA. Both
      systems are similar in their performance in predicting metastatic behaviour in
      tumours from individual patients.

PMID- 16632189
TI  - Determinants of seeking of primary care for lower urinary tract symptoms: the
      Krimpen study in community-dwelling men.
AB  - OBJECTIVES: To determine which factors predict seeking of primary care among men
      with lower urinary tract symptoms (LUTS). METHODS: A longitudinal, population
      based study with a follow-up period of 6.5 yr was conducted among 1688 men aged
      50-78 yr. The following data were collected: prostate volume (using transrectal
      ultrasonometry), urinary flow rate, ultrasound-estimated postvoid residual urine
      volume, generic and disease-specific quality of life (QOL), and symptom severity
      (International Prostate Symptom Score [IPSS]). Information on the seeking of
      primary care by all participants during 2 yr of follow-up was collected from the
      general practitioner's (GP) record using a computerised search engine and a
      manual check of electronically selected files. RESULTS: Prostate volume, postvoid
      residual volume, IPSS, and social generic QOL are important determinants of first
      GP consultation in men with LUTS. Measurements (physical urologic parameters) and
      self-reported items (symptom severity and QOL) contribute almost equally to GP
      consultation in these men. CONCLUSIONS: Both measurements of prostate volume and
      postvoid residual urine volume and self-reported information about symptoms or
      QOL can help to select those who will benefit from medical care and to reassure
      those men not likely to need help in the near future.

PMID- 16632190
TI  - Retroperitoneal fibrosis after chemotherapy.
AB  - We report the case of a patient with a non-Hodgkin lymphoma, who after a standard
      chemotherapy protocol, developed retroperitoneal fibrosis (RPF) in the absence of
      radiotherapy or other known causes. The final diagnosis was reached with the
      microscopic examination of tissue obtained by fine-needle aspiration and true-cut
      biopsy of the retroperitoneal mass. RPF can be related to chemotherapy alone.

PMID- 16632191
TI  - Hybrid SPECT-CT: an additional technique for sentinel node detection of patients
      with invasive bladder cancer.
AB  - OBJECTIVES: To explore the feasibility of performing lymphoscintigraphy combined
      with computed tomography (CT) for preoperative detection of sentinel lymph nodes
      in patients with invasive bladder cancer. MATERIALS: Six consecutive patients
      scheduled for radical cystectomy underwent lymphoscintigraphy after transurethral
      injection of Albures-technetium 99m in the detrusor muscle peritumourally both
      with planar imaging and with single-photon emission computed tomography/CT
      (SPECT/CT). CT for anatomic fusion was performed directly after the SPECT/CT and
      both investigations were combined to a fused image. Radical cystectomy started
      with extended lymphadenectomy and intraoperative detection of sentinel nodes with
      both Geiger probe and dye marker. The conventional planar lymphoscintigraphies
      and the fused SPECT/CT were compared with each other and with the outcome of
      intraoperative sentinel node detection and final histopathologic analyses.
      RESULTS: The method allowed anatomically detailed preoperative visualisation of
      21 sentinel nodes in five of the six patients, whereas planar pictures only
      visualised two sentinel nodes in two of six patients. Two patients had lymph node
      metastases and in the other four the nodes were negative. The combined method
      visualised all metastatic sentinel nodes, whereas planar lymphoscintigraphy
      detected only one of six node metastases. CONCLUSIONS: The combination of
      lymphoscintigraphy with CT enhanced preoperative anatomic localisation of
      sentinel nodes in bladder cancer and aided in the identification of sentinel
      nodes during surgery. The yield of detected sentinel nodes, both metastatic and
      nonmetastatic, was markedly increased using the combined method compared to
      conventional planar lymphoscintigraphy.

PMID- 16632192
TI  - Antimuscarinics and cognitive function.

PMID- 16632193
TI  - Re: Francesco Porpiglia, Carlo Terrone, Julien Renard, Sussana Grande, Francesca
      Musso, Marco Cossu, Francesca Vacca and Roberto Mario Scarpa. Transcapsular
      adenomectomy (Millin): a comparative study, extraperitoneal laparoscopy versus
      open surgery. Eur urol 2006;49:120-6.

PMID- 16632194
TI  - Tenascin-C induced signaling in cancer.
AB  - Tenascin-C is an adhesion modulatory extracellular matrix molecule that is highly
      expressed in the microenvironment of most solid tumors. High tenascin-C
      expression reduces the prognosis of disease-free survival in patients with some
      cancers. The possible role of tenascin-C in tumor initiation and progression is
      addressed with emphasis on underlying signaling mechanisms. How tenascin-C
      affects malignant transformation, uncontrolled proliferation, angiogenesis,
      metastasis and escape from tumor immunosurveillance is summarized. Finally, we
      discuss how the phenotypes of tenascin-C knock-out mice may help define the roles
      of tenascin-C in tumorigenesis and how this knowledge could be applied to cancer
      therapy.

PMID- 16632195
TI  - Combination of Wu Lin San and Shan Zha ameliorates substance P-induced
      hyperactive bladder via the inhibition of neutrophil NADPH oxidase activity.
AB  - Substance P (SP) via neurokinin type 1 receptor activates leukocytes to produce
      burst release of reactive oxygen species (ROS) and increases leukocytes adhesion
      to the vessels in the inflamed bladder. Activation of neutrophil nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase activity may contribute to the
      neutrophil ROS production. We explored the therapeutic effect of traditional
      Chinese formula for urinary dysfunction, Wu Lin San (WLS), and a modified formula
      WLS plus Shan Zha (WLSSZ) on SP-induced bladder hyperactivity. We evaluated WLS,
      Shan Zha, and WLSSZ effect on neutrophils NADPH oxidase activity in SP-stimulated
      neutrophils in vitro, and isovolumetric cystometrogram and ROS activity in vivo
      in anesthetized rat bladder with SP stimulation. Our results showed that WLS,
      Shan Zha, and WLSSZ inhibited SP-induced NADPH oxidase activity in an order
      WLSSZ>Shan Zha>WLS. Exogenous SP enhanced systemic vasodilation, bladder
      hyperactivity and bladder ROS. One week of oral administration of WLS or WLSSZ
      significantly reduced SP-induced bladder ROS amount and leukocyte accumulation
      and ameliorated the hyperactive bladder response. The therapeutic action was
      better in WLSSZ than in WLS. Our results indicate that a modified formula Wu Lin
      San plus Shan Zha can potentially ameliorate SP-induced neurogenic inflammation
      possibly via the inhibition of leukocyte NADPH oxidase activity.

PMID- 16632196
TI  - Amphetamine-elicited striatal Fos expression is attenuated in neurotensin null
      mutant mice.
AB  - Neurotensin (NT) has been suggested to interact with dopamine systems in
      different forebrain sites to exert both antipsychotic- and psychostimulant-like
      effects. We previously found that genetic or pharmacological manipulations that
      disrupt endogenous NT signaling attenuate antipsychotic drug-induced Fos
      expression in the dorsolateral and central striatum but not other striatal
      regions. To assess the role of NT in psychostimulant responses, we examined the
      ability of d-amphetamine (AMP) to induce Fos in wild-type and NT null mutant
      mice. AMP-elicited Fos expression was significantly attenuated in the medial
      striatum of NT null mutant mice, but was unaffected in other striatal
      territories. Similar results were obtained in rats and mice pretreated with the
      high affinity neurotensin receptor (NTR1) antagonist SR 48692. The effect of the
      NTR1 antagonist was particularly apparent in the striatal patch (striosome)
      compartment, as defined by mu-opioid receptor immunoreactivity. These data
      suggest that NT is required for the full activation by AMP of medial striatal
      neurons.

PMID- 16632197
TI  - Characterization of cortical spreading depression in adult well-nourished and
      malnourished rats submitted to the association of pilocarpine-induced epilepsy
      plus streptozotocin-induced hyperglycemia.
AB  - Spreading depression was characterized in adult rats rendered epileptic by
      pilocarpine (350 mg/kg, i.p.) and thereafter made hyperglycemic with (i.p.) 60
      mg/kg streptozotocin. Groups treated with only one of the above drugs, as well as
      control groups treated with their vehicles (saline and citrate buffer,
      respectively) were also studied. The animals treated with pilocarpine or
      streptozotocin presented, as a common feature, a reduction in the spreading
      depression propagation rate. However, they differed by the fact that pilocarpine,
      in some cases, blocked spreading depression propagation, whereas streptozotocin
      did not block it at all. In early-malnourished animals, streptozotocin-effects,
      but not pilocarpine-effects on spreading depression were attenuated. The
      treatment with both drugs did not potentiate their individual reducing effects on
      spreading depression propagation, irrespective of the animals' early nutritional
      status. These results extend previous observations on rats treated with both
      drugs separately, confirming their impairing action on spreading depression
      propagation. They also indicate that early malnutrition is more effective in
      changing the streptozotocin effects on spreading depression, as compared to the
      pilocarpine-effects. Since such effects were observed at adulthood, they indicate
      that the early malnutrition-induced cortical changes responsible for the here
      described effects are long-lasting.

PMID- 16632198
TI  - Myofibrillogenesis regulator 1 gene (MR-1) mutation in an Omani family with
      paroxysmal nonkinesigenic dyskinesia.
AB  - Two recurrent missense mutations (c.20C>T: A7V; c.26C>T: A9V) in the gene
      encoding the myofibrillogenesis regulator 1 (MR-1) have been shown to cause
      autosomal dominant paroxysmal nonkinesigenic dyskinesia (PNKD) in 13 families of
      primarily European ancestry. Here we report an Omani PNKD family with seven
      affected family members and autosomal dominant inheritance. Our linkage analysis
      provided consistent positional evidence that the MR-1 gene could be the
      responsible disease gene. Sequence analysis identified a MR-1 missense mutation
      (c.20C>T; A7V) in the affected family members, whereas it was not present in five
      unaffected family members and 129 population controls. Taking into account that
      previous haplotype analyses did not reveal evidence for common founders among
      several PNKD families, our present findings strengthen three implications: (1)
      autosomal dominant PNKD seems to be a homogenous disorder, for which the MR-1
      gene is the major disease gene; (2) mainly two recurrent MR-1 missense mutations
      (57% V7, 43% V9) account for the genetic variance of familial PNKD; (3) it
      supports current evidence that some of the recurrent MR-1 mutations may have
      arisen independently by de novo mutation at functionally convergent key sites of
      the brain-specific MR-1L isoform.

PMID- 16632199
TI  - Regional differences in vulnerability of the cerebellar foliations of rats
      exposed to neonatal X-irradiation.
AB  - The purpose of the present study was to elucidate regional differences in the
      vulnerability of cerebellar foliations of rats exposed to X-irradiation. Effects
      of X-irradiation on foliations were examined with respect to histological changes
      in Purkinje cells and Bergmann glial fibers by calbindin-D28k (CB) and glial
      fibrillary acidic protein (GFAP) immunohistochemistry, respectively. Wistar rats
      were exposed to X-irradiation (1.5 Gy) on postnatal day (PND) 1. At 3 weeks of
      age, the cerebellum was examined. The cerebella of rats exposed to X-irradiation
      showed smaller and abnormal foliations compared with controls. Fewer cerebellar
      foliations due to fusion with neighboring folia were observed in folia I-III and
      VIa-VII. Moreover, the extent of such abnormalities was more severe in the latter
      folia. CB-immunoreactive (IR) Purkinje cells exhibited thin, short, disoriented
      dendrites that had invaded the granular layer or white matter. On the other hand,
      GFAP-IR Bergmann glial fibers had not extended their processes into the molecular
      layer perpendicular to the pial surface, and they appeared thin and disoriented.
      Accordingly, the above cerebellar abnormalities were more severe in folia I-III,
      VIa-VII and X than in other regions. In contrast to the histological alterations
      in these folia, there were no apparent qualitative differences in folia IV-V
      between X-irradiated and controls. These findings indicate regional difference in
      the vulnerability of cerebellar folia to X-irradiation. Such differences might be
      attributed to the cerebellar neurogenetic gradient.

PMID- 16632200
TI  - Effect of estrogen on the expression of occludin in ovariectomized mouse brain.
AB  - The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB),
      formed by interactions of tight junctions (TJs) in the endothelia or the choroids
      plexus, respectively, are important diffusion barriers between systemic
      circulation and neural tissue of the central nervous system (CNS).
      Epidemiological incidence of degenerative changes in the CNS is significantly
      higher in postmenopausal women than in men, suggesting an important role of
      ovarian steroids for CNS integrity in women. To elucidate the role estrogen in
      the maintenance of paracellular diffusion barriers in the CNS, changes in the
      expression of occludin, a TJ protein, following ovariectomy (OVX), as well as the
      effect of estrogen on the expression of occludin in OVX female brain, were
      examined in mice. Immunoreactivity of occludin was found in brain endothelial
      capillaries, choroids plexus, ependyma, and aqueduct. In OVX brain, expression of
      occludin mRNA and protein was decreased a little but significantly relative to a
      sham control brain at the estrous stage. Estrogen (17beta estradiol)
      significantly up-regulated occludin mRNA levels in OVX mice. Together, these
      results suggest that occludin is an important structural element in both the BBB
      and BCSFB, and that expression of occludin in female brain tissue is sensitive to
      estrogen levels.

PMID- 16632201
TI  - Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish
      population is not associated with dementia.
AB  - Mutations in leucine-rich repeat kinase 2 gene (LRRK2) have been associated with
      idiopathic Parkinson's disease (PD), as well as pleomorphic neurodegenerative
      pathology, including Alzheimer's disease. One specific LRRK2 mutation, G2019S,
      was reported in 18% of people with PD of Ashkenazi descent, supporting a founder
      effect in this population. To determine if this mutation is also associated with
      dementia in the Ashkenazim, we screened 192 elderly Ashkenazi Jewish (AJ)
      individuals in a longitudinal aging and cognition study, of whom 49 (25.5%) had
      dementia. Two non-demented individuals harbored the mutation (2/143, 1.4%), but
      no individuals with dementia. Neither person with the mutation had Parkinson's
      disease. Therefore, the LRRK2 mutation has a relatively high frequency in the AJ
      population, is not fully penetrant for parkinsonism in the elderly, and does not
      appear to be commonly associated with late-onset dementia.

PMID- 16632202
TI  - Cerebral activation during thermal stimulation of patients who have burning mouth
      disorder: an fMRI study.
AB  - The pathophysiology of burning mouth disorder (BMD) is not clearly understood,
      but central neuropathic mechanisms are thought to be involved. The aim of this
      study was to gain insight into the pathophysiology associated with BMD by using
      functional magnetic resonance imaging (fMRI). Areas of brain activation following
      thermal stimulation of the trigeminal nerve of eight female patients with BMD
      (mean age 49.1+/-10.1) were mapped using fMRI and compared with those of eight
      matched pain-free volunteers (mean age 50.3+/-12.3). Qualitative and quantitative
      differences in brain activation patterns between the two study groups were
      demonstrated. BMD patients displayed greater fractional signal changes in the
      right anterior cingulate cortex (BA 32/24) and bilateral precuneus than did
      controls (p<0.005). The control group showed larger fractional signal changes in
      the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left
      lingual gyrus, and cerebellum than did the BMD patients (p<0.005). In addition,
      BMD patients had less volumetric activation throughout the entire brain compared
      to the control group. Overall, BMD patients displayed brain activation patterns
      similar to those of patients with other neuropathic pain conditions and appear to
      process thermal painful stimulation to the trigeminal nerve qualitatively and
      quantitatively different than pain-free individuals. These findings suggest that
      brain hypoactivity may be an important feature in the pathophysiology of BMD.

PMID- 16632204
TI  - Copper transfer studies between the N-terminal copper binding domains one and
      four of human Wilson protein.
AB  - Human Wilson protein functions in the secretory pathway to insert copper
      ultimately into the multicopper oxidase ceruloplasmin and also plays a role in
      the excretion of excess copper to the bile. This copper-transporting P-type
      ATPase possesses six N-terminal cytosolic copper-binding domains contained within
      an approximately 72 amino acid consensus motif and the first four of these
      domains, denoted WLN1-4, are implicated in copper acquisition from the
      metallochaperone HAH1, whereas the domains closest to the membrane portion of the
      enzyme, WLN5-6, are essential for copper transport across the membrane. In order
      to test our hypothesis that copper transfer occurs between domains in the N
      terminus of Wilson protein, we expressed and purified to homogeneity copper
      binding domains 1, 3, 4, 5-6, and 6, denoted by WLN1, WLN3, WLN4, WLN5-6, and
      WLN6, respectively. Since we determined WLN1 and WLN4 to have the highest and
      lowest isoelectric points (6.77 and 3.85, respectively) and thus are readily
      separated via ion exchange chromatography, we developed a copper transfer assay
      between these domains. We anaerobically incubated either Cu(I)-WLN1 with apo-WLN4
      or apo-WLN1 with Cu(I)-WLN4, then separated these domains and quantified the
      amount of copper that migrates from one domain to another by ICP-MS. Regardless
      of whether we start with Cu(I)-WLN1 or Cu(I)-WLN4 as the initial copper donor, we
      demonstrate facile copper transfer between WLN1 and WLN4, thereby demonstrating
      the feasibility of copper transfer between these domains in vivo.

PMID- 16632205
TI  - Homocysteine and other structurally-diverse amino thiols can alter pancreatic
      beta cell function without evoking cellular damage.
AB  - Homocysteine and related amino thiols, homocysteic acid, cysteic acid,
      homocysteine sulphinic acid and cysteine sulphinic acid have been labelled as
      neurotoxins. Homocysteine thiolactone, a metabolic derivative of homocysteine, is
      cytotoxic to endothelial cells and other cell lineages. Since pancreatic beta
      cells share many phenotypic similarities with neuronal cells, the present study
      uses clonal pancreatic BRIN-BD11 cells to investigate possible detrimental
      effects of these amino thiols on insulin secretion and pancreatic beta cell
      function. Insulin secretion was concentration-dependently inhibited at both basal
      (1.1 mM) and stimulatory (16.7 mM) glucose by homocysteine, homocysteine
      thiolactone and homocysteine sulphinic acid. Cysteic acid concentration
      dependently inhibited insulin secretion at 16.7 mM glucose. Cell viability was
      not compromised by any of the amino thiols. Insulin secretory responses to
      alanine were inhibited by homocysteine, homocysteine thiolactone, homocysteic
      acid and cysteic acid. Insulin secretion in the presence of elevated Ca(2+) and
      forskolin were lowered by all amino thiols, except homocysteic acid. The
      secretory responsiveness to PMA, GLP-1 and KCl were only impaired in the presence
      of homocysteine and homocysteine thiolactone. These findings indicate that
      homocysteine, homocysteine thiolactone and, to a lesser extent, other amino
      thiols cause dysfunctional insulin secretion from pancreatic beta cells.

PMID- 16632206
TI  - Early neonatal and postweaning social emotional deprivation interferes with the
      maturation of serotonergic and tyrosine hydroxylase-immunoreactive afferent fiber
      systems in the rodent nucleus accumbens, hippocampus and amygdala.
AB  - The impact of early emotional experience on the development of serotonergic and
      dopaminergic fiber innervation of the nucleus accumbens, hippocampal formation
      and the amygdala was quantitatively investigated in the precocious rodent Octodon
      degus. Two animal groups were compared: 1) degus which were repeatedly separated
      from their parents during the first three postnatal weeks, after weaning they
      were individually reared in chronic social isolation and 2) controls which were
      reared undisturbed with their families. In the deprived animals 5
      hydroxytryptamine-immunoreactive fiber densities were increased in the core
      region of the nucleus accumbens (up to 126%), in the central nucleus of the
      amygdala (up to 112%) and in the outer subregion of the dentate gyrus stratum
      moleculare (up to 149%), whereas decreased fiber densities were detected in the
      dentate subgranular layer (down to 86%) and in the stratum lacunosum of the
      hippocampal cornu ammonis region 1 (down to 86%). Tyrosine hydroxylase
      immunoreactive fiber densities were increased in the core (up to 115%) and shell
      region (up to 113%) of the nucleus accumbens of deprived animals, whereas
      decreased fiber densities (down to 84%) were observed in the hilus of the dentate
      gyrus. In the stratum granulosum and subgranular layer the fiber densities
      increased up to 168% and 127% respectively. In summary, these results indicate
      that the postnatal establishment of the monoaminergic innervation of limbic areas
      is modulated in response to early emotional experience, and that this
      environmental morphological adaptation is highly region specific.

PMID- 16632207
TI  - Transient rhythmic network activity in the somatosensory cortex evoked by
      distributed input in vitro.
AB  - The initiation and maintenance of physiological and pathophysiological
      oscillatory activity depends on the synaptic interactions within neuronal
      networks. We studied the mechanisms underlying evoked transient network
      oscillation in acute slices of the adolescent rat somatosensory cortex and
      modeled its underpinning mechanisms. Oscillations were evoked by brief spatially
      distributed noisy extracellular stimulation, delivered via bipolar electrodes.
      Evoked transient network oscillation was detected with multi-neuron patch-clamp
      recordings under different pharmacological conditions. The observed oscillations
      are in the frequency range of 2-5 Hz and consist of 4-12 mV large, 40-150 ms wide
      compound synaptic events with rare overlying action potentials. This evoked
      transient network oscillation is only weakly expressed in the somatosensory
      cortex and requires increased [K+]o of 6.25 mM and decreased [Ca2+]o of 1.5 mM
      and [Mg2+]o of 0.5 mM. A peak in the cross-correlation among membrane potential
      in layers II/III, IV and V neurons reflects the underlying network-driven basis
      of the evoked transient network oscillation. The initiation of the evoked
      transient network oscillation is accompanied by an increased [K+]o and can be
      prevented by the K+ channel blocker quinidine. In addition, a shift of the
      chloride reversal potential takes place during stimulation, resulting in a
      depolarizing type A GABA (GABAA) receptor response. Blockade of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), N-methyl-D-aspartate (NMDA), or
      GABA(A) receptors as well as gap junctions prevents evoked transient network
      oscillation while a reduction of AMPA or GABA(A) receptor desensitization
      increases its duration and amplitude. The apparent reversal potential of -27 mV
      of the evoked transient network oscillation, its pharmacological profile, as well
      as the modeling results suggest a mixed contribution of glutamatergic, excitatory
      GABAergic, and gap junctional conductances in initiation and maintenance of this
      oscillatory activity. With these properties, evoked transient network oscillation
      resembles epileptic afterdischarges more than any other form of physiological or
      pathophysiological neocortical oscillatory activity.

PMID- 16632208
TI  - A mechanism for the inactivation of Ca2+/calmodulin-dependent protein kinase II
      during prolonged seizure activity and its consequence after the recovery from
      seizure activity in rats in vivo.
AB  - Seizure is a form of excessive neuronal excitation and seizure-induced neuronal
      damage has profound effects on the prognosis of epilepsy. In various seizure
      models, the inactivation of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      occurs during seizure activity preceding neuronal cell death. CaMKII is a
      multifunctional protein kinase enriched in the brain and involved in various ways
      the regulation of neuronal activity. CaMKII inactivation during seizure activity
      may modify neuronal cell survival after seizure. However, the mechanism for
      CaMKII inactivation and its consequence after seizure recovery remain to be
      elucidated yet. In the present study, we employed a prolonged seizure model by
      systemic injection of kainic acid into rats and biochemically examined the
      activity state of CaMKII. In status epilepticus induced by kainic acid, not only
      the inactivation of CaMKII in brain homogenate, but also a shift in the
      distribution of CaMKII protein from the soluble to particulate fraction occurred
      in both hippocampus and parietal cortex. The particulate CaMKII showed a large
      decrease in the specific activity and a concurrent large increase in the
      autophosphorylation ratio at Thr-286 (alpha) and at Thr-287 (beta). In contrast,
      the soluble CaMKII showed normal or rather decreased specific activity and
      autophosphorylation ratio. After 24 h of recovery from kainic acid-induced status
      epilepticus, all such changes had disappeared. On the other hand, the total
      amount of CaMKII was decreased by 35% in hippocampus and 20% in parietal cortex,
      but the existing CaMKII was indistinguishable from those of controls in terms of
      the autonomous activity ratio, specific activity and autophosphorylation ratio.
      Thus, CaMKII inactivation in kainic acid-induced status epilepticus seems to be
      derived not from simple degradation of the enzyme, but from the formation of the
      autophosphorylated, inactivated and sedimentable CaMKII. Such a form of CaMKII
      may be important during pathological conditions in vivo in preventing excessive
      CaMKII activation due to Ca2+ overload.

PMID- 16632209
TI  - Altered hypothalamo-pituitary-adrenal and sympatho-adrenomedullary activities in
      rats bred for high anxiety: central and peripheral correlates.
AB  - Wistar rats have been selectively bred for high (HABs) or low (LABs) anxiety
      related behavior based on results obtained in the elevated-plus maze. They also
      display robust behavioral differences in a variety of additional anxiety tests.
      The present study was undertaken to further characterize physiological substrates
      that contribute to the expression of this anxious trait. We report changes in
      brain and peripheral structures involved in the regulation of both the
      hypothalamo-pituitary-adrenal (HPA) and sympatho-adrenal systems. Following
      exposure to a mild stressor, HABs displayed a hyper-reactivity of the HPA axis
      associated with a hypo-reactivity of the sympatho-adrenal system and a lower
      serotonin turnover in the lateral septum and amygdala. At rest, HABs showed a
      higher adrenal weight and lower tyrosine hydroxylase and phenylethanolamine-N
      methyltransferase mRNAs expression in their adrenals than LABs. In the anterior
      pituitary, HABs also exhibited increased proopiomelanocortin and decreased
      vasopressin V1b receptor mRNAs expression, whereas glucocorticoid receptor mRNA
      levels remained unchanged. These results indicate that the behavioral phenotype
      of HABs is associated with peripheral and central alterations of endocrine
      mechanisms involved in stress response regulation. Data are discussed in relation
      to coping strategies adopted to manage stressful situations. In conclusion, HABs
      can be considered as an useful model to study the etiology and pathophysiology of
      stress-related disorders and their neuroendocrine substrates.

PMID- 16632210
TI  - Differences in club drug use between heterosexual and lesbian/bisexual females.
AB  - Although there has been much empirical research documenting current trends in
      club drug use among gay and bisexual men, little research has addressed the
      variance among lesbian, bisexual, or heterosexual women. Using data collected
      through time-space sampling from dance clubs in New York City during 2005
      (N=1104), this study explored sexual identity variance among women in the
      reported use of six club drugs: methamphetamine, cocaine, MDMA, ketamine, GHB,
      and LSD. Significant differences were found in that younger women were more
      likely to be active club drug users. Lesbian and bisexual women reported
      significantly higher lifetime rates of ecstasy, cocaine, methamphetamine, and LSD
      use compared to heterosexual women. These data suggest a need to better
      understand the influence of sexual orientation and sexual culture in relation to
      club drug use and to tailor health promotion efforts to meet the needs of various
      groups of club drug using women.

PMID- 16632213
TI  - Pathologic reporting and special diagnostic techniques for melanoma.
AB  - Pathologists play a central role in the management of cutaneous melanoma in
      determining that a tumor is a melanoma, whether or not it is primary or
      metastatic, and whether or not the margins of excision are tumor free and in
      evaluating prognostic indicators from examination of the primary tumor and, where
      appropriate, lymph nodes, including the sentinel nodes.

PMID- 16632214
TI  - Novel imaging techniques in melanoma.
AB  - Cutaneous melanoma is one of the most deadly malignancies. Although it accounts
      for approximately 4% of all cancer cases, it ac-counts for approximately 79% of
      skin cancer-related deaths. In the past few years, the nuclear medicine platform
      used in the management of melanoma has extended to biochemical and structural
      imaging. In clinical practice, integrated positron emission tomography/CT devices
      allow anatomic and metabolic characterization of meta-static disease in a single
      study. Similarly, more accurate localization of sentinel nodes in a 3-D space now
      is feasible with hybrid single photon emission CT/CT system. In translational
      research, [18F]fluorodeoxyglucose probes have been designed to optimize the
      detection of melanoma tumor sites in vivo.

PMID- 16632215
TI  - The role of lymphoscintigraphy in the detection of lymph node drainage in
      melanoma.
AB  - Lymphatic drainage of the skin cannot be predicted based on clinical guidelines
      developed more than 100 years ago. Approximately 30% of patients experience
      drainage from the skin to unexpected lymph node sites rather than those specified
      by these guidelines, and therefore these outdated assumptions should no longer be
      used to plan surgery. A possible survival benefit has been shown for the early
      detection and surgical removal of metastatic disease in the draining lymph nodes,
      and therefore, clinicians must obtain accurate lymphatic mapping for each patient
      who has intermediate thickness melanoma to plan appropriate surgical therapy.
      Lymphoscintigraphy can be used to accurately define the precise position of each
      true sentinel node in every patient, whether these nodes lie in a standard node
      field or in an unusual location. In this way, lymphoscintigraphy has a direct
      beneficial impact on the surgical management of patients who have melanoma.

PMID- 16632216
TI  - Surgical management of primary cutaneous melanoma: excision margins and the role
      of sentinel lymph node examination.
AB  - Surgical strategies for managing patients who have primary cutaneous melanoma
      have changed dramatically over the past 30 years. More conservative excision
      margins have been shown to be adequate, and routine complete lymph node
      dissection (CLND)has been abandoned since the sentinel node (SN) biopsy technique
      was introduced. Knowledge of a patient's SN status not only provides a reliable
      guide to prognosis, but also allows CLND to be avoided in 80% to 85% of patients.
      Recent clinical trial results suggest that SN biopsy, with immediate CLND if an
      SN is positive,confers a survival advantage in those who have metastatic disease
      in regional nodes. Minimally invasive and noninvasive methods of SN assessment,
      such as magnetic resonance spectroscopy, are being evaluated.

PMID- 16632217
TI  - The conundrum of follow-up: should it be abandoned?
AB  - This article critically evaluates the practice of follow-up for patients who have
      undergone treatment for a primary melanoma without evidence of metastases. One
      conclusion from this analysis is that the benefits of routine imaging and blood
      testing are insufficient to warrant a place in routine follow-up. Few patients
      who have metastases are identified in this fashion and even fewer survive because
      they underwent these tests. Far more often, false-positive results occur, which
      invariably cause unnecessary concern, lead to additional unnecessary testing, and
      may even result in needless surgery. Based on the evidence available, the
      relevance of follow-up per se must even be challenged. No convincing evidence
      exists that regional control, survival, and quality of life improve through
      surveillance. Other reasons for surveillance may be present, but these are less
      imperative. The present findings challenge current practice.

PMID- 16632218
TI  - Molecular upstaging of sentinel lymph nodes in melanoma: where are we now?
AB  - The presence of lymph node metastasis is the best predictor of disease
      progression and overall survival in patients who have melanoma. Lymphatic mapping
      and selective lymphadenectomy allows directed pathologic analysis of the node or
      nodes most likely to have metastatic disease. To diagnose metastatic disease in
      SLNs reliably requires a coordinated effort by nuclear medicine physicians,
      surgeons, and pathologists. Errors may occur if quality assurance is not
      emphasized at any point during the process. This, along with the presence of
      occult metastatic disease, may lead to disease recurrence and progression, even
      when SLN histologically are free of disease. Molecular up-staging of occult
      malignant disease has the potential to provide important information to
      facilitate the diagnosis, surveillance, and treatment of cancer. The detection of
      occult tumor cells in SLNs and blood provides a powerful tool for assessing early
      regional and systemic disease spread in patients who have AJCC stage II and III
      not only melanoma but also other solid tumors. The use of varying panels of
      markers from different laboratories has hampered the interpretation of data and
      made it difficult to unravel the merits of molecular up staging. Molecular
      approaches have made a major impact on the field of infectious disease and should
      one day be of equal usefulness in the diagnosis of cancer.

PMID- 16632219
TI  - New American Joint Commission on Cancer staging system for melanoma: prognostic
      impact and future directions.
AB  - Accurate melanoma staging is critical in establishing management strategies and
      estimating disease relapse. Combined with assessment of comorbidities and
      understanding treatment toxicities, risk assessment is central to offering
      appropriate surgical or systemic therapies. The American Joint Commission on
      Cancer (AJCC) melanoma staging system provides survival estimates within
      anatomically defined disease categories. Newer prognostic factors and methods of
      prognostic analyses can augment predictions for the presence of micro-metastatic
      disease and further define the risk for relapse. This article highlights relevant
      changes, evidence supporting future incorporation of more recently defined
      prognostic variables, novel approaches used as adjuncts to the current staging
      system, and future directions of the AJCC staging committee.

PMID- 16632220
TI  - Radiation therapy in the management of cutaneous melanoma.
AB  - The role of RT in the management of melanoma is complex and spans the entire
      course of the disease. To provide optimal management of patients who have
      melanoma, radiation oncologists are an integral part of a multidisciplinary team.
      Appropriate integration of radiation into the management plan can improve
      locoregional control and alleviate symptoms from meta-static disease. The
      specific role of RT in locoregional disease is being refined. It is likely that
      current developments in radiation treatment technology will be applicable to
      melanoma. These should improve the therapeutic ratio by enhancing the tumoricidal
      effects of RT without increasing toxicity.

PMID- 16632221
TI  - Isolated limb perfusion in regional melanoma.
AB  - Adjuvant perfusion to excision of a primary melanoma cannot be recommended
      because of its limited effect. In patients who have frequently recur-ring
      resectable locoregional melanoma, perfusion may provide valuable loco-regional
      disease control by decreasing the number of recurrences and lesions per
      recurrence. Randomized studies are needed to further establish the role of
      perfusion as an adjuvant treatment for resectable recurrences of melanoma.
      Unresectable limb melanoma is the primary indication for perfusion. Better
      response rates tend to be seen when TNF-a is used in patients who have a high
      tumor load. Repeat perfusion is feasible, resulting in response rates similar to
      those of a first perfusion for locoregional melanoma. Older age itself is not a
      contraindication for perfusion. The long-term health-related quality of life of
      survivors of melanoma who underwent treatment with perfusion is comparable to
      that of their healthy peers in the general Dutch population.

PMID- 16632222
TI  - Surgical management of distant metastases.
AB  - Although the location of metastases is of prognostic importance in stage IV
      melanoma, as seen in the revised AJCC staging classification system and other
      studies, certain guiding principles apply to patients who have any stage IV
      disease. Close follow-up of any patient who has melanoma may identify surgically
      resectable metastatic disease, although this method is controversial. Components
      of this monitoring may include careful questioning to determine symptoms, such as
      cough, abdominal pain, or headaches; physical examination for evidence of skin,
      soft tissue, and lymph node metastases; and screening tools, such as radiographs
      and laboratory tests. Identifying patients who have metastatic disease at the
      earliest stage possible is crucial for surgical resection to be an option.
      Patients should also be thoughtfully evaluated for the possibility of a complete
      surgical re-section. Complete metastectomy, regardless of the anatomic site,
      confers survival advantages not seen with other treatment modalities. This
      aggressive surgical approach should be tempered with the knowledge that
      incomplete resections put patients at increased risk without any proven survival
      benefit, and should be reserved only for palliation of symptoms. Systemic
      adjuvant therapies for stage IV melanoma are evolving, but do not yet confer the
      survival advantage of complete surgical resection. Until novel drug therapies
      show efficacy and significantly prolong survival in patients who have stage IV
      disease, careful consideration should be given to a complete metastectomy if
      technically feasible.

PMID- 16632223
TI  - Evaluation of immunotherapy in the treatment of melanoma.
AB  - These data show that the extraordinary potency of the immune system can be
      harnessed to control or destroy melanoma. The proven impact has been limited for
      patients who have melanoma, but has been dramatic and lasting in selected groups.
      Recent improvements in understanding of immunology, including mechanisms
      regulating immune responses and methods of tumor cell escape, are already
      yielding improved clinical outcomes and potential avenues for extending benefits
      to more patients. Thus, although the full potential of this treatment modality
      has yet to be realized, the vanguard of the "treatment of tomorrow" has clearly
      arrived.

PMID- 16632224
TI  - Management of metastatic melanoma 2005.
AB  - The management of metastatic melanoma in 2005 remains a major clinical challenge.
      Multidisciplinary treatment planning and careful attention to sites of
      metastases, tumor biology, and comorbid conditions are critical to making the
      best clinical decisions for individual patients. No standard of care exists
      because no systemic therapies have yet shown efficacy in phase III trials. Single
      agent or combination chemotherapy has not impacted over-all survival, and
      response rates are of short duration. High-dose IL-2 produces durable responses
      in a small subset (7%) of highly selected patients and has considerable toxicity
      and quality-of-life trade-offs. Biochemotherapy results in overall higher
      responses, but its impact on overall survival has been disappointing and its
      toxicity and expense are considerable. Re-searchers are further investigating
      biochemotherapy modifications with maintenance biotherapy and CNS consolidation
      in effort to increase durability of responses and prevent or delay the
      devastating sequela of CNS metastases. Despite a disappointing past, the
      advancement of science and a better understanding of critical cellular targets
      and pathways make the future of melanoma research encouraging. Clinical trials
      are actively studying novel immune potentiators, cytotoxics, and targeted
      therapies. Combinations of these new agents will likely be necessary to advance
      the treatment of the dis-ease. All patients should be encouraged to participate
      in clinical trials.

PMID- 16632225
TI  - Randomized trials in melanoma: an update.
AB  - No effective therapy for metastatic melanoma exists. Polychemotherapy or
      chemoimmunotherapy have not shown survival benefits. Vaccines have shown little
      activity in stage IV disease. To advance the identification of effective agents,
      new drugs can and should be offered as first-line treatment. Efforts must be made
      to improve understanding of the biology of malignant melanoma. Too many phase III
      trials have been conducted with a poor understanding of the mechanism of action
      of the involved drugs.

PMID- 16632226
TI  - Why is it so difficult to stop psychiatric drug treatment? It may be nothing to
      do with the original problem.
AB  - In this paper, I argue that the problems that occur after discontinuation or
      reduction of long-term psychiatric drug treatment may be caused by the process of
      drug withdrawal itself, rather than representing the course of the underlying
      illness. Adverse effects induced by discontinuation of psychiatric medication
      include: (1) a somatic discontinuation syndrome that includes psychological
      symptoms which may be mistaken for relapse, (2) a rapid onset psychotic reaction
      after withdrawal of both conventional neuroleptic drugs and some atypicals,
      notably clozapine (sometimes referred to as supersensitivity psychosis), (3) a
      psychological reaction to withdrawal, which may be mistaken for relapse or may
      itself precipitate relapse, (4) a genuine relapse of the underlying condition
      precipitated by the process of withdrawal. The implications of these effects
      include the possibility that much of the research on maintenance treatment is
      flawed and that the recurrent nature of psychiatric conditions may sometimes be
      iatrogenic. If withdrawal induced adverse effects could be effectively managed,
      the success of drug discontinuation might be much greater than usually assumed
      and might outweigh the disadvantages of continued treatment.

PMID- 16632227
TI  - Considering the major mental disorders as clinical expressions of periodic
      pathological oscillations of the overall operating mode of brain function.
AB  - The consideration of the collective significance of the shared characteristics
      and overlaps in the clinical expression and pharmacological responses of the
      major mental disorders (namely, schizophrenia, bipolar disorders, obsessive
      compulsive disorder, anxieties/phobias, borderline syndrome and possibly others)
      supports the following: (1) These disorders have a common, initial
      neurodevelopmental origin. (2) They occur probabilistically on some of "at-risk"
      individuals whose pre-existing, extreme, temperamental/structural variance
      confers vulnerability for such occurrence. (3) Lastly, each of these syndromes
      can be considered as a clinical expression of oscillations (i.e., a switch to a
      pathologically ordered phase) of the overall, common operating mode of brain
      function. This mode based on a particular-for-our-brain, emergent quality of
      complexity, normally ensures the synchrony, coordination, subtlety and robust
      flexibility in the expression of the components of each of the various higher
      faculties of the brain, namely, the faculty of: (1) mood modulation; (2)
      coordination of feelings, thoughts and the responses to the external world; and
      (3) keeping constrain and limited but appropriate input of primitive drives. The
      conclusions in this paper have important ramifications in rethinking the current
      nosological procrustean flawed classification and the neurodevelopmental origin
      of the major mental disorders as well as the biases shown in selecting subjects
      for research. It also opens opportunities in the future development of novel,
      effective, economical and harmless therapies that will restore and maintain the
      normal phase of the operating mode of brain function. For example, the patient
      can wear an appropriate electronic device that sends a particular type of signal
      to the brain which will affect remission and prevent relapses without harm. We
      can thus avoid the use of pharmacological agents which have limited
      effectiveness, severe, long-term side-effects and financial burden to the
      patient.

PMID- 16632228
TI  - TGF-beta1 is the possible shared pathogenetic factor on a patient with muscular
      dystrophy and congenital hepatic fibrosis.

PMID- 16632229
TI  - Metal speciation, phytochemicals and Helicobacter pylori infection.
AB  - Helicobacter pylori (HP) acquired in childhood is an important risk factor for
      gastric carcinoma. Once colonization is established, infection may be carried for
      life. The relationship between food intake and HP infection, the presence of
      metals and phytochemicals closely associated with oxidative stress within
      everyday diet are important topics to be considered. The possible anti-HP effects
      of phytochemicals, prooxidant effects exerted in the presence of metal species,
      intimate relations between some metals and HP, bivalent effects of some metal
      species in cancer, interactions between metal species and phytochemicals in HP
      infection are the topics, which require further research. Formulas or diets
      enriched with phytochemicals and metals against HP and, which are devoid of
      metals known to favour the growth of HP, may be suggested as the supplements to
      the classical treatment regimens. The importance of collective consideration of
      HP, metal species and phytochemicals should be emphasized.

PMID- 16632230
TI  - Antibodies as oncogenes: a hypothesis.
AB  - We would like to put forward the hypothesis that cancer patients may produce
      autoantibodies that promote uncontrolled cell growth and thereby function as
      oncogenes. Dying cells release proteins that stimulate the production of
      autoantibodies, an event also known to occur during the earliest stages of tumor
      growth. If some of these autoantibodies are directed against cell surface hormone
      receptors, they could oligomerize the receptors and inadvertently transmit growth
      signals. The abnormal signals could result in uncontrolled cell proliferation
      and, eventually, oncogenesis. Thus, some specific autoantibodies from among the
      large repertoires of autoantibodies present in the sera of cancer patients are,
      in reality, oncogenes. If such oncogenic autoantibodies are indeed present and
      can be identified, inhibition of their molecular action may be an effective
      therapeutic modality.

PMID- 16632231
TI  - Central role of supporting cells in cochlear homeostasis and pathology.
AB  - HYPOTHESIS: Supporting cells have a crucial role in degenerative and regenerative
      events of primary sensorial hair cells of the organ of Corti. This new role
      should determine future studies about pathophysiology of hearing loss and its
      regenerative treatment. SUPPORTING EVIDENCE: Recent findings suggest an active
      role of supporting cells in the maintenance of hair cell function and structure.
      Evidences of high energy consumption and close proximity to auditory nervous
      fibers suggesting K+ active exchange, preferential expression of specific
      proteins and antigens, presence of glucocorticoids receptors, affinity for
      cisplatin and regenerative potential give the supporting cells an important role
      in homeostasis of the organ of Corti and in some specific diseases affecting this
      structure. CONCLUSION: As well as glial cells provide protection and regeneration
      to neural tissues, supporting cells may provide the necessary metabolic and
      electrolitic conditions for hair cells mechanical and bioelectrical function.
      This opens new possibilities for the treatment of apparently "irreversible"
      destruction of the inner ear.

PMID- 16632232
TI  - Comparison of type 1, type 2, and atypical ketosis-prone diabetes at 4 years of
      diabetes duration.
AB  - CONTEXT: Atypical ketosis-prone diabetes (KPD) is frequently detected in obese
      individuals at diagnosis of diabetes, yet its precise pathophysiology is not
      understood. AIM: The hypothesis tested in this study states that while
      individuals with atypical KPD are phenotypically similar to those with type 2
      diabetes, metabolically, they behave more like individuals with autoimmune type 1
      diabetes. METHODS: Thirty-seven individuals of Black, Hispanic, or White
      background and a diagnosis of diabetes mellitus for an average duration of 4
      years participated in this cross-sectional study. Ten, 12, and 15 subjects had
      type 1, atypical, and type 2 diabetes, respectively. Insulin secretion was
      evaluated by a mixed-meal test. Insulin sensitivity and fuel oxidation were
      assessed by simultaneous euglycemic hyperinsulinemic clamp and indirect
      calorimetry. Lastly, a 12-h insulin withdrawal test was performed. RESULTS:
      Insulin secretion, insulin sensitivity, and the insulin withdrawal tests yielded
      significant differences for type 1 vs. atypical diabetes and type 1 vs. type 2
      diabetes, while there were no significant differences between atypical vs. type 2
      diabetes. The indirect calorimetry showed higher-than-normal basal nonprotein
      respiratory quotients (RQs) and lower-than-normal insulin-stimulated nonprotein
      RQs across the three study groups. CONCLUSIONS: After 4 years from diabetes
      diagnosis and while far from optimal glycemic control, atypical KPD resembles
      type 2 diabetes phenotypically and metabolically as well. Therefore, this study
      supports the classification of atypical KPD as ketosis-prone type 2 diabetes, and
      the concept that metabolic inflexibility occurs in the presence of insulin
      resistance in type 1 and type 2 diabetes.

PMID- 16632233
TI  - Prandial insulin substitution with insulin lispro or insulin lispro mid mixture
      vs. basal therapy with insulin glargine: a randomized controlled trial in
      patients with type 2 diabetes beginning insulin therapy.
AB  - PURPOSE: To compare the effects of prandial insulin therapy focusing on
      postprandial glucose control vs. basal insulin therapy focusing on fasting
      glucose control in patients with type 2 diabetes. METHODS: This was an open
      label, randomized, parallel, three-arm multicenter trial in patients with type 2
      diabetes starting insulin treatment. Patients (n=159) were randomly assigned to
      24-week treatment with 3x daily insulin lispro, 3x daily lispro mid mixture
      (MidMix; 50% lispro, 50% protaminated lispro), or 1x daily insulin glargine; oral
      antihyperglycemic agents were discontinued. Primary end point was the
      postprandial glucose excursion 2 h after breakfast at the end of study. Secondary
      outcomes included HbA1c, self-monitored blood glucose profiles, hypoglycemic
      episodes, body weight, and patient satisfaction. RESULTS: At the end of study,
      glucose excursions 2 h after breakfast were significantly lower with lispro and
      MidMix than with glargine (P<.001 for each vs. glargine): lispro, -0.6+/-2.0
      mmol/l; MidMix, +0.8+/-2.4 mmol/l; glargine, +2.5+/-2.4 mmol/l. Fasting glucose
      decreases were significantly greater with glargine (-2.6+/-2.4 mmol/l) than with
      lispro or MidMix (-0.9+/-2.2 mmol/l; +0.9+/-1.8 mmol/l). Nevertheless, HbA1c
      decreased by 1.1% (lispro) and 1.2% (MidMix), vs. 0.3% with glargine.
      Hypoglycemic episodes were rare with 1-1.5 self-reported episodes per 100 patient
      days. CONCLUSIONS: In patients with type 2 diabetes starting insulin, 3x daily
      prandial treatment with a rapid-acting analog focusing on postprandial glucose
      values enabled better control of postprandial and circadian blood glucose
      profiles than once-daily glargine, in spite suboptimal fasting glucose levels,
      which targets fasting glucose values. These results support studies suggesting
      that control of postprandial hyperglycemia plays a key role in achieving HbA1c
      targets.

PMID- 16632234
TI  - Glycemic control with regular versus lispro insulin sliding scales in
      hospitalized Type 2 diabetics.
AB  - PURPOSE: The aim of this study was to compare glycemic control with either
      regular or lispro insulin sliding scales in hospitalized Type 2 diabetics who
      were not using insulin as outpatients. METHODS: Forty-three patients with Type 2
      diabetes, who were taking oral agents only, were admitted to a medical inpatient
      service and randomized to receive either regular or lispro insulin sliding scale.
      Oral agents for diabetes were held upon admission and patients were followed
      throughout their hospital stay. RESULTS: There was no significant difference
      (P>.05) between the average finger-stick blood glucose (FSBG) in the regular
      insulin group (157.78+/-40.16 mg/dl) and the lispro insulin group (152.04+/-27.71
      mg/dl). No significant difference was found between the daily dose of insulin
      (regular, 5.83+/-5.01 units; lispro, 4.27+/-3.40 units), total amount of insulin
      used during hospitalization (regular, 11.87+/-10.78 units; lispro, 12.77+/-14.39
      units), glucose excursion (regular, 110.13+/-25.86 mg/dl; lispro, 106.77+/-52.65
      mg/dl), or length of hospital stay (regular, 2.33+/-1.23 days; lispro, 2.69+/
      1.59 days). CONCLUSION: No significant difference in glycemic control was found
      in hospitalized Type 2 diabetic patients who received either regular or lispro
      insulin sliding scales. Both insulin sliding scales used in this study are
      inadequate to achieve current recommended glycemic targets in this patient
      population, when used as the only inpatient treatment for diabetes.

PMID- 16632235
TI  - Falls as a complication of diabetes mellitus in older people.
AB  - OBJECTIVES: The aims of this study were to determine the incidence of falls in a
      group of elderly patients with diabetes and to assess for the prevalence of risk
      factors for falls in this population. DESIGN: This is a population-based study
      with questionnaire-based interviews. SETTING: The setting for this study was the
      London District General Hospital outpatient department. PARTICIPANTS: Seventy
      seven patients with diabetes, aged over 65 years, randomly selected whilst
      attending for general diabetic annual review. Patients with dementia, blindness,
      and immobility and those who were unable to give informed consent were excluded
      from this study. MEASUREMENTS: The incidence of falls in the last 12 months was
      used. Information was collected on the incidence of hypoglycaemic episodes, the
      presence of other medical conditions, visual impairment, and peripheral
      neuropathy, the use of medications and walking aids, and HbA1C and blood pressure
      control. RESULTS: The incidence of falls was 39%. Falls occurred more frequently
      in female patients and patients of increasing age. Falls occurred more frequently
      in patients with poor diabetic control [risk ratio (RR)=7.83 (2.948-20.799), chi2
      value=6.422]; patients requiring assistance with mobility: for those mobile with
      a stick [RR=1.839 (1.048-3.227), chi2=4.619]; and those who had previously
      suffered a stroke [RR=1.929 (1.143-3.257), chi2=4.615]. CONCLUSION: We provide
      evidence that poorly controlled diabetes and conditions associated with
      complications of diabetes are associated with an increased risk of falling in
      older people. We recommend early recognition of the multiple causes of falls in
      the older diabetic patient and prompt referral of this group of patients to a
      specialist falls clinic.

PMID- 16632236
TI  - Major complications have an impact on total annual medical cost of diabetes:
      results of a database analysis.
AB  - BACKGROUND: Type 2 diabetes mellitus is a common, chronic, and costly disease,
      and its prevalence is increasing in major industrialized countries. Diabetes has
      indeed a high social impact mainly because of its chronic complications.
      OBJECTIVE: The aim of this study was to analyze the direct medical costs
      attributable to Type 2 diabetes mellitus and its determinants, as assessed in a
      diabetologic center (DC) in Italy. METHODS: We conducted a retrospective
      longitudinal cost of care study; Type 2 diabetic patients who visited between
      January 2001 and August 2002 were randomly selected from the database of the DC
      of Portogruaro. Cost data collected included hospitalizations, visits,
      diagnostics, and pharmacological therapies and were quantified and analyzed in
      the perspective of the National Health Service (NHS). RESULTS: Two hundred ninety
      nine diabetic patients were extracted, with a mean/patient follow up of 476 days.
      Mean age was 67.5 years and males represented 67.2% of the sample. The average
      annual health care cost was found to be euro1909.67 per patient; pharmacological
      therapies accounted for the greatest proportion of direct medical costs (52%),
      followed by hospitalization (28%) and diagnostic exams (11%). Annual costs
      increased with the number of diabetes related comorbidities, from euro1039 to
      3141 per patient in participants with none or more than two complications,
      respectively. CONCLUSION: Long-term complications carry a considerable impact on
      total annual medical cost. Our study demonstrates that an increase in the number
      of comorbidities is directly associated with an increase of Type 2 diabetes cost.
      Strategies aimed at preventing the onset of diabetic complications are likely to
      reduce medical costs in the long run, while improving patients' health.

PMID- 16632237
TI  - The influence of ethnicity on health-related quality of life in diabetes
      mellitus: a population-based, multiethnic study.
AB  - OBJECTIVES: The aims of this study were to evaluate the influence of ethnicity on
      health-related quality of life (HRQoL) in diabetic participants using both
      profile [the Short-Form 36 (SF-36)] and single-index (the SF-6D) instruments and
      to evaluate the usefulness of the SF-6D as a summary measure for the SF-36.
      RESEARCH DESIGN AND METHODS: Using data from a cross-sectional, population-based
      survey of Chinese, Malay, and Indians in Singapore, we analyzed the influence of
      ethnicity and other variables on each SF-36 scale and SF-6D scores using linear
      regression models to adjust for the influence of known determinants of HRQoL.
      RESULTS: Data from 309 diabetic respondents were analyzed. Compared with other
      ethnicities, Indians were most likely to report impaired HRQoL. The unadjusted
      influence of ethnicity on HRQoL exceeded the minimum clinically important
      difference (MCID) for all SF-36 scales (MCID: 5 points) and the SF-6D (MCID:
      0.033 points). After adjusting for gender, age, and education, the influence of
      Chinese ethnicity exceeded the MCID for all SF-36 scales, except vitality (VT)
      and mental health (MH), as well as for the SF-6D. The influence of Malay
      ethnicity exceeded the MCID only for the SF-36 MH scale and the SF-6D. The
      influence of ethnicity on HRQoL persisted after adjusting further for other
      determinants of HRQoL. The SF-6D reflected the ethnic trends for some but not all
      SF-36 scales. CONCLUSIONS: After adjusting for demographic, socioeconomic, and
      other factors known to influence HRQoL, ethnicity remained an important factor
      influencing HRQoL in this population-based multiethnic sample of diabetic Asians.
      Further studies to identify modifiable factors explaining the ethnic disparities
      in HRQoL among diabetic participants are needed. The SF-6D may be a useful
      summary measure for the SF-36.

PMID- 16632238
TI  - Comparison of the antioxidant and vascular effects of gliclazide and
      glibenclamide in Type 2 diabetic patients: a randomized crossover study.
AB  - The aim of the present study is to compare the short-term effects of gliclazide
      and glibenclamide on the oxidative state and vascular endothelium function of
      Type 2 diabetic patients in an observer-blinded, randomized crossover study.
      Thirteen Type 2 diabetic patients were enrolled: one group of seven patients took
      daily 160 mg of gliclazide for the first 4 weeks and then daily 5 mg of
      glibenclamide for the next 4 weeks; another group of six patients took daily 5 mg
      of glibenclamide for the first 4 weeks and 160 mg of gliclazide for the next 4
      weeks. Forearm blood flow (FBF) measurement for endothelial function and
      biochemical analyses were conducted before and after each crossover treatment.
      Four weeks of treatment with either sulfonylurea showed the similar
      antihyperglycemic effects and enhancement of the peak FBF and total reactive
      hyperemic flow (flow debt repayment: FDR) during reactive hyperemia. Treatment
      with gliclazide resulted in the significant reduction to about 60% of baseline in
      urinary 8-iso-prostaglandin F2alpha (8iPGF2alpha) excretion while no such change
      was detected in the glibenclamide period. The increases in peak FBF and FDR were
      in parallel with its anti-hyperglycemic effect, but not with antioxidant state.
      Results suggest that gliclazide and glibenclamide can protect vascular
      endothelium from hyperglycemia-induced injury in Type 2 diabetic patients.

PMID- 16632239
TI  - Laser damage to retinal ganglion cells: the effect on circadian rhythms.
AB  - Laser therapy (LRx) may affect the retinal ganglion cells (RGC), which play a
      role in circadian rhythms. This study assesses the effect of LRx on the circadian
      variation of cortisol (F), measured in 20 Type 2 diabetic patients (DM), 10
      following LRx for diabetic proliferative retinopathy (DPR), and 10 control (CTR)
      without laser Rx or retinopathy. The diurnal F variation in the CTR followed a
      normal pattern. Compared with CTR, the F levels of the DPR group were
      significantly higher at 1600 and 2400 h (10.2+/-2.5 vs. 6.9+/-4.0 microg/dl,
      P<.05, and 6.4+/-2.5 vs. 2.6+/-1.7 microg/dl, P<.001, respectively). These
      results provide evidence that DM patients, following bilateral LRx for
      proliferative diabetic retinopathy, experienced nocturnal hypercortisolemia and
      loss of normal circadian cortisol variation, probably secondary to LRx damage to
      the RGC.

PMID- 16632240
TI  - Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated
      with micro- and macrovascular complications in Type 1 diabetic patients.
AB  - OBJECTIVE: There are no large studies in Type 1 diabetic patients that have
      examined the relation between soluble adhesion molecules and micro- and
      macrovascular outcomes, although the risks of such complications are high.
      Therefore, the main objective is to examine the relationship between soluble (s)
      vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin and retinopathy,
      albuminuria, and cardiovascular disease (CVD) in Type 1 diabetic patients.
      METHODS: Cross-sectional data on 540 Type 1 diabetic patients, with a mean age of
      40 years and diabetes duration of 22 years, from the EURODIAB Prospective
      Complications Study (PCS) were analysed. Retinopathy was assessed by centrally
      graded retinal photographs. Albumin excretion rate (AER) was used to define micro
      and macroalbuminuria. CVD was defined as having physician diagnosed myocardial
      infarction (MI), stroke, coronary artery bypass graft (CABG) or angina, or
      Minnesota coded ischaemic electrocardiograms (ECGs). RESULTS: Unadjusted, there
      was a positive relationship between sVCAM-1 and sE-selectin with nonproliferative
      and proliferative retinopathy, micro- and macroalbuminuria, and CVD. After
      adjustment for age, sex, duration of diabetes, systolic blood pressure (BP), LDL
      cholesterol, fasting triglycerides (TGs), smoking, body mass index (BMI), and
      glycated haemoglobin, as well as other complications, the strongest significant
      associations were shown between sVCAM-1 and macroalbuminuria, with an odds ratio
      of 1.83 (1.33-2.53) for every 100 ng/ml increase in sVCAM-1. CONCLUSIONS: In this
      large sample of Type 1 diabetic patients, it was shown that sVCAM-1 and sE
      selectin have positive associations with retinopathy, albuminuria, and CVD. This
      suggests that adhesion molecules are important in the pathogenesis of vascular
      complications in Type 1 diabetes.

PMID- 16632241
TI  - Systemic IGF-I treatment inhibits cell death in diabetic rat retina.
AB  - Diabetic retinopathy can result in apoptotic cell death of retinal neurons, as
      well as significant visual loss. It is further known that insulin-like growth
      factor (IGF) levels are reduced in diabetes and that IGF-I can prevent cell death
      in many cell types. In this study, we tested the hypothesis that systemic
      treatment with IGF-I could inhibit death of neuroretinal cells in diabetic rats
      by examining the expression of proapoptotic markers. In diabetic rat retina, the
      number of TUNEL-immunoreactive cells increased approximately sixfold in the
      photoreceptor layer (P<.001) and eightfold in the inner nuclear layer (INL;
      P<.001); phospho-Akt (p-Akt; Thr 308) immunoreactivity increased eightfold in the
      ganglion cell layer (GCL; P<.001) and threefold in the INL (P<.01). Subcutaneous
      IGF-I treatment significantly reduced the number of TUNEL (P<.001) and p-Akt
      immunoreactive retinal cells (P<.05) in diabetic rats approximately to the level
      of the nondiabetic group. Qualitative results showed that caspase-3 and BAD
      immunoreactivities were also elevated in diabetes and reduced in IGF-I-treated
      animals. Elevated TUNEL and p-Akt immunoreactivities were localized to distinct
      cell layers in the retina of diabetic rats. Early intervention with systemic IGF
      I reduced the presence of proapoptotic markers indicative of neuroretinal cell
      death, despite ongoing hyperglycemia and weight loss. The eye is a special
      sensory organ, and these data show that cell loss in the nervous system, even in
      uncontrolled diabetes, can be prevented by IGF-I administration.

PMID- 16632242
TI  - Contrast-enhanced ultrasound examination of lymph nodes in different types of
      lymphoma.
AB  - BACKGROUND: Since the tumor growth depends on the formation of feeding vessels,
      color/power Doppler ultrasonography (US) has been used to evaluate the vascular
      flow images of lymph nodes (LNs) in order to differentiate benign LNs from
      malignant LNs or lymphoma from metastatic carcinoma. METHODS: We performed
      color/power Doppler ultrasonography (US) using Levovist (LV) to evaluate the
      vascular patterns in the LNs of 10 patients with different types of lymphoma. The
      patterns were classified as central, peripheral, or avascular type. RESULTS:
      Vascular flow was identified in 9 of 10 LNs and it was enhanced with LV in all
      cases. The vascular pattern of the LNs was of the central type in all seven B
      cell lymphoma patients and one of two T-cell lymphoma patients and of the
      peripheral type in the remaining T-cell lymphoma patient. The avascular type
      pattern was observed in one Hodgkin lymphoma patient even with LV. DISCUSSION:
      Typical vascular patterns might be associated with certain subtypes of lymphoma,
      and LV appears to improve the diagnostic value of Doppler US.

PMID- 16632243
TI  - Mutant p53 protein in the serum of patients with colorectal cancer: Correlation
      with the level of carcinoembryonic antigen and serum epidermal growth factor
      receptor.
AB  - INTRODUCTION: Enzyme-linked immunosorbent assay (ELISA) was used for analysis of
      serum mutant p53 protein, carcinoembryonic antigen (CEA), and epidermal growth
      factor receptor (EGFR). Serum samples were obtained from 48 patients with
      colorectal cancer (CRC) and a control group of twenty healthy individuals.
      RESULTS: The results demonstrated a significant increase of serum mutant p53,
      EGFR, and CEA levels in CRC patients compared to the control group (P<0.001 for
      each). Mutant p53 protein was significantly different in the different CRC grades
      (P=0.028). p53, CEA, and EGFR can differentiate successfully between different
      CRC grades and normal control (P<0.001 for each). Sensitivities of p53, CEA, and
      EGFR were 39.6, 31, and 71%, respectively. There was no correlation between CEA,
      EGFR, and p53 indicating that these variables were independent. Positive status
      of serum CEA and (or) p53 was found in 29 out of 48 (60%) patients. Also,
      positive status of serum CEA and (or) EGFR was found in 39 out of 48 (81%)
      patients. CONCLUSION: Thus, the simultaneous determination of p53 or EGFR
      combined with the CEA may increase the sensitivity to diagnose CRC patients and
      may aid in disease prognosis.

PMID- 16632244
TI  - Study of the topographic distribution of ets-1 protein expression in invasive
      breast carcinomas in relation to tumor phenotype.
AB  - BACKGROUND: Ets-1 is a transcription factor, implicated in the regulation of
      expression of various genes'. The aim of the present study was to investigate the
      expression of ets-1 protein in invasive breast carcinomas and its correlation
      with classic clinicopathological parameters, patients' survival and various
      biological markers. METHODS: Immunohistochemistry was performed in paraffin
      embedded tissue specimens from 149 invasive breast carcinomas to detect the
      proteins ets-1, p53, topoisomerase IIalpha, matrix metalloproteinase-7 (MMP-7)
      and urokinase-type plasminogen activator receptor (uPAR). Results were subjected
      to univariate and multivariate statistic analysis. RESULTS: Ets-1 protein was
      detected in the 77.9% of the cases in the cytoplasm, in the 46.3% in the nucleus
      of the malignant cells, and in stromal fibroblasts as well. Cytoplasmic ets-1 was
      inversely correlated with nuclear and histologic grade of the tumor (p=0.004 and
      0.033, respectively) and topoisomerase IIotaalpha (p=0.057), while nuclear ets-1
      showed a positive association with p53 (p=0.002). Stromal ets-1 revealed a
      negative correlation with estrogen receptors (ER) (p=0.003) and a positive one
      with stromal uPAR and MMP-7 as well (p=0.048 and 0.066, respectively). The
      univariate statistic analysis showed nuclear ets-1 to be related to a shortened
      overall survival of the postmenopausal patients (p=0.032). CONCLUSIONS: Ets-1
      seems to be related to a different tumor phenotype according to its topographic
      distribution, with nuclear localization being associated with decreased apoptotic
      potential of the malignant cells through its relation to the mutant p53 protein,
      cytoplasmic being related to a favorable tumor phenotype and stromal ets-1 being
      related to tumor invasion.

PMID- 16632245
TI  - Targeted nanoblobs spot treat cancer and heart disease.

PMID- 16632246
TI  - Detection of activated, TIMP-free MMPs.
AB  - MMP inhibitor-tethered resins provide a method for detection of activated MMPs in
      tissues. These measurements will help to elucidate in situ mechanisms of MMP
      activation, further our understanding of the tumor microenvironment, and
      facilitate development of MMP-inhibitor therapy.

PMID- 16632247
TI  - New images evoke FAScinating questions.
AB  - Two recent papers in Science reported the X-ray structures of the large,
      organizationally distinct animal and fungal fatty acid synthases at 5 A. These
      new structural insights have unexpected implications for enzyme function for the
      other "iterative" and "assembly line" megasynthases.

PMID- 16632248
TI  - Involvement of reactive oxygen species and reactive nitrogen species in the wound
      response of Dasycladus vermicularis.
AB  - We investigated the signaling events involved in the wound response of the marine
      macroalga Dasycladus vermicularis, finding nitric oxide (NO) production in
      relation to injury. The addition of exogenous H2O2 to aliquots of injured algae
      accelerated the kinetics of NO production in the wounded region. Similarly, the
      addition of an NO donor caused an increase in detectable H2O2 around the site of
      injury. By wounding or incubating uninjured algae with an NO donor, peroxidase
      activity was enhanced. Based on the use of selected pharmacological probes, our
      results indicate that H2O2 production involves the upstream activation of
      signaling events similar to those observed in the physiology of higher plants.

PMID- 16632249
TI  - Biosynthesis of the terpene phenalinolactone in Streptomyces sp. Tu6071: analysis
      of the gene cluster and generation of derivatives.
AB  - Phenalinolactones are terpene glycosides with antibacterial activity. A striking
      structural feature is a highly oxidized gamma-butyrolactone of elusive
      biosynthetic origin. To investigate the genetic basis of the phenalinolactones
      biosynthesis, we cloned and sequenced the corresponding gene cluster from the
      producer strain Streptomyces sp. Tu6071. Spanning a 42 kbp region, 35 candidate
      genes could be assigned to putatively encode biosynthetic, regulatory, and
      resistance-conferring functions. Targeted gene inactivations were carried out to
      specifically manipulate the phenalinolactones pathway. The inactivation of a
      sugar methyltransferase gene and a cytochrome P450 monoxygenase gene led to the
      production of modified phenalinolactone derivatives. The inactivation of a
      Fe(II)/alpha-ketoglutarate-dependent dioxygenase gene disrupted the biosynthetic
      pathway within gamma-butyrolactone formation. The structure elucidation of the
      accumulating intermediate indicated that pyruvate is the biosynthetic precursor
      of the gamma butyrolactone moiety.

PMID- 16632250
TI  - Design and characterization of a metalloproteinase inhibitor-tethered resin for
      the detection of active MMPs in biological samples.
AB  - Matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, are implicated
      in tumor progression. We describe herein the development of a resin-immobilized,
      broad-spectrum synthetic MMP inhibitor for selective binding of the active forms
      of MMPs from different experimental samples. We confirmed the activity-based
      binding of MMPs to the inhibitor-tethered resin with purified human recombinant
      MMP-2, -9, and -14, samples of cultured cells, and tissue extracts. Our results
      show that only the free active MMPs, and not the zymogens or MMP/TIMP (enzyme
      protein inhibitor) complexes, bound specifically to the resin. In our comparison
      of benign and carcinoma tissue extracts, we detected active MMP-2 and MMP-14
      forms only in the cancerous tissue samples, indicating that a pool of the tumor
      MMPs is free of endogenous inhibitors (TIMPs), and is thus likely to contribute
      to proteolytic events that precipitate tumor metastasis.

PMID- 16632251
TI  - Functional analysis of the validamycin biosynthetic gene cluster and engineered
      production of validoxylamine A.
AB  - A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in
      validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory
      genes, 5 genes related transport, transposition/integration or tellurium
      resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic
      pathway was proposed, with assignment of the required genetic functions confined
      to the sequenced region. A cluster of eight reassembled genes was found to
      support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo
      inactivation of the putative glycosyltransferase gene (valG) abolished the final
      attachment of glucose for VAL production and resulted in accumulation of the VAL
      A precursor, validoxylamine, while the normal production of VAL-A could be
      restored by complementation with valG. The role of valG in the glycosylation of
      validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay.

PMID- 16632252
TI  - Selective kinase inhibition by exploiting differential pathway sensitivity.
AB  - Protein kinase inhibitors are optimized to have high affinity for their intended
      target(s) to elicit the desired cellular effects. Here, we asked whether
      differences in inhibitory sensitivity between two kinase signaling pathways,
      controlled by the cyclin-dependent kinases Cdk1 and Pho85, can be sufficient to
      allow for selective targeting of one pathway over the other. We show the oxindole
      inhibitor GW297361 elicits a Pho85-selective response in cells despite having a
      20-fold greater biochemical potency for Cdk1 in vitro. We provide evidence that
      partial inhibition of Pho85 is sufficient to activate Pho85-dependent signaling,
      but partial inhibition of Cdk1 is not sufficient to block Cdk1-dependent cell
      proliferation. Identification of highly sensitive kinases may provide a means to
      achieve selective perturbation of kinase signaling pathways complementary to
      efforts to achieve maximal differences between in vitro IC50 values.

PMID- 16632253
TI  - Structure of the EntB multidomain nonribosomal peptide synthetase and functional
      analysis of its interaction with the EntE adenylation domain.
AB  - Nonribosomal peptide synthetases are modular proteins that operate in an assembly
      line fashion to bind, modify, and link amino acids. In the E. coli enterobactin
      NRPS system, the EntE adenylation domain catalyzes the transfer of a molecule of
      2,3-dihydroxybenzoic acid to the pantetheine cofactor of EntB. We present here
      the crystal structure of the EntB protein that contains an N-terminal
      isochorismate lyase domain that functions in the synthesis of 2,3
      dihydroxybenzoate and a C-terminal carrier protein domain. Functional analysis
      showed that the EntB-EntE interaction was surprisingly tolerant of a number of
      point mutations on the surface of EntB and EntE. Mutational studies on EntE
      support our previous hypothesis that members of the adenylate-forming family of
      enzymes adopt two distinct conformations to catalyze the two-step reactions.

PMID- 16632254
TI  - Rapid synthesis and in situ screening of potent HIV-1 protease dimerization
      inhibitors.
AB  - A library of dimerization inhibitors of HIV-1 protease is described based on
      crosslinked interfacial peptides. The 54 component library was designed to
      contain two modifications to the starting structure, one each in the Northern and
      Southern fragments. A rapid synthesis and in situ screening method in microtiter
      plates was developed to facilitate the generation and evaluation of the library
      members. More than 90% of the doubly modified agents were more potent than their
      respective singly mutated parent compounds, and five of the most potent
      dimerization inhibitors of HIV-1 protease described to date were identified. The
      free energy of binding for the combined two modifications was generally found to
      be additive, demonstrating the predictive value of earlier libraries.

PMID- 16632255
TI  - Biomimetic facially amphiphilic antibacterial oligomers with conformationally
      stiff backbones.
AB  - A foldamer has been designed with a conformationally stiff backbone that is
      facially amphiphilic. The oligomer has excellent antimicrobial activity and was
      found to be 18 times more active toward bacterial cells than human red blood
      cells. The oligomer is built from arylamide bonds around a central 4,6-dicarboxy
      pyrimidine ring. The conformation was studied by X-ray crystallography and
      solution NMR spectroscopy. Density-functional (DFT) calculations were performed
      to guide the design. These calculations accurately predicted the overall
      conformation as well as NMR chemical shifts. Antibacterial activity was
      demonstrated against E. coli, a gram-negative strain, and B. subtilis, a gram
      positive strain. The minimal inhibitory concentration is 0.8 microg/ml.

PMID- 16632256
TI  - An in vitro screen of bacterial lipopolysaccharide biosynthetic enzymes
      identifies an inhibitor of ADP-heptose biosynthesis.
AB  - The lipopolysaccharide (LPS)-rich outer membrane of gram-negative bacteria
      provides a protective barrier that insulates these organisms from the action of
      numerous antibiotics. Breach of the LPS layer can therefore provide access to the
      cell interior to otherwise impermeant toxic molecules and can expose vulnerable
      binding sites for immune system components such as complement. Inhibition of LPS
      biosynthesis, leading to a truncated LPS molecule, is an alternative strategy for
      antibacterial drug development in which this vital cellular structure is
      weakened. A significant challenge for in vitro screens of small molecules for
      inhibition of LPS biosynthesis is the difficulty in accessing the complex
      carbohydrate substrates. We have optimized an assay of the enzymes required for
      LPS heptose biosynthesis that simultaneously surveys five enzyme activities by
      using commercially available substrates and report its use in a small-molecule
      screen that identifies an inhibitor of heptose synthesis.

PMID- 16632257
TI  - Biochemical suppression of small-molecule inhibitors: a strategy to identify
      inhibitor targets and signaling pathway components.
AB  - Identification of small-molecule targets remains an important challenge for
      chemical genetics. We report an approach for target identification and protein
      discovery based on functional suppression of chemical inhibition in vitro. We
      discovered pirl1, an inhibitor of actin assembly, in a screen conducted with
      cytoplasmic extracts. Pirl1 was used to partially inhibit actin assembly in the
      same assay, and concentrated biochemical fractions of cytoplasmic extracts were
      added to find activities that suppressed pirl1 inhibition. Two activities were
      detected, separately purified, and identified as Arp2/3 complex and Cdc42/RhoGDI
      complex, both known regulators of actin assembly. We show that pirl1 directly
      inhibits activation of Cdc42/RhoGDI, but that Arp2/3 complex represents a
      downstream suppressor. This work introduces a general method for using low
      micromolar chemical inhibitors to identify both inhibitor targets and other
      components of a signaling pathway.

PMID- 16632258
TI  - Evidence for the role of the monB genes in polyether ring formation during
      monensin biosynthesis.
AB  - Ionophoric polyethers are produced by the exquisitely stereoselective oxidative
      cyclization of a linear polyketide, probably via a triepoxide intermediate. We
      report here that deletion of either or both of the monBI and monBII genes from
      the monensin biosynthetic gene cluster gave strains that produced, in place of
      monensins A and B, a mixture of C-3-demethylmonensins and a number of minor
      components, including C-9-epi-monensin A. All the minor components were
      efficiently converted into monensins by subsequent acid treatment. These data
      strongly suggest that epoxide ring opening and concomitant polyether ring
      formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as
      previously thought. Consistent with this, homology modeling shows that the
      structure of MonB-type enzymes closely resembles the recently determined
      structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.

PMID- 16632259
TI  - [Proteomics and breast cancer: new perspectives and limitations].
AB  - From differential analysis for the identification of biomarkers, to functional
      analysis for the evidencing of new therapeutic targets, proteomics brings new
      comprehensive information for a better understanding of the molecular basis of
      oncology and new perspectives for the clinic. However the major limitation of
      proteomic investigations and more generally of post-genomic approaches remains
      the molecular and cellular complexity of biological systems. This will be
      illustrated with the case of breast cancer.

PMID- 16632260
TI  - [Identification and management of hereditary breast-ovarian cancers (2004
      update)].
AB  - BACKGROUND: Since the last recommendations, up to 2500 new references had been
      published on that topic. METHODOLOGY: On the behalf of the health Minister, the
      Ad Hoc Committee consisted of 13 experts carried out a first version revisited by
      five additional experts who critically analyzed the first version of the report.
      MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer
      deleterious mutations of BRCA1 and BRCA2 than previously thought. The screening
      of ovarian cancer is still not an attractive option while in contrast MRI may be
      soon for these young women with dense breast, the recommended option for breast
      cancer screening. The effectiveness of prophylactic surgeries is now well
      established. French position is to favor such surgeries with regard to a quality
      of life in line with the expected benefit, and providing precise and standardized
      process described in the recommendation. CONCLUSIONS: Due to methodological
      flaws, the low power and a short follow-up of the surveys, this statement cannot
      however aspire to a high stability.

PMID- 16632261
TI  - [Use of molecular subtyping methods to investigate two nosocomial outbreaks due
      to Salmonella Livingstone in Sfax hospital, Tunisia].
AB  - OBJECTIVE: The aim of the study was to investigate two nosocomial outbreaks due
      to Salmonella Livingstone in a pediatric ward in Sfax hospital using molecular
      typing techniques. MATERIALS AND METHODS: We included 84 strains of S.
      Livingstone isolated from patients hospitalized in a pediatric ward between
      November 1999 through August 2002 in addition to one environmental sample. Three
      epidemiological unrelated strains of S. Livingstone were also tested. The
      molecular typing techniques were: plasmid analysis, enterobacterial repetitive
      intergenic consensus (ERIC-PCR), random amplification of polymorphic DNA (RAPD
      PCR) and pulsed field gel electrophoresis (PFGE). RESULTS: The plasmid analysis
      and the ERIC-PCR generated a similar profile for outbreak isolates including the
      environmental sample while the epidemiologically unrelated strains demonstrated
      distinct patterns. The RAPD-PCR applied on 20 strains showed three patterns but
      one profile was predominating. All the strains isolate of S. Livingstone, except
      the veterinary strain, could not be typed by PFGE. CONCLUSION: Using the
      molecular typing techniques, we showed that these two outbreaks in the pediatric
      ward were due to the clonal spread of a single strain of S. Livingstone. The
      identification of the source of contamination and the improvement of hygiene
      conditions are required.

PMID- 16632262
TI  - Identification and functional characterization of levS, a gene encoding for a
      levansucrase from Leuconostoc mesenteroides NRRL B-512 F.
AB  - A Leuconostoc mesenteroides NRRL B-512 F levansucrase gene, (levS), was isolated,
      sequenced and cloned in Escherichia coli. The recombinant enzyme was shown to be
      a fructosyltransferase producing a polymer identified by (13)C-NMR as levan.
      Based on sequence analysis, we found that this levansucrase is a mosaic protein,
      bearing structural features of glucosyltransferases in the amino and carboxy
      terminal regions similarly to inulosucrase from Leuconostoc citreum. The
      phylogenetic analysis of the C-terminal region domain of levansucrases from L.
      mesenteroides demonstrates that they group together into a novel putative sub
      family of genes and evolved long before all other glucosyltransferases, while
      their catalytic domain structure is species related.

PMID- 16632263
TI  - Follicular dynamics and plasma FSH and progesterone concentrations during
      follicular deviation in the first post-ovulatory wave in Nelore (Bos indicus)
      heifers.
AB  - The objective of the present study was to characterize ovarian follicular
      dynamics and hormone concentrations during follicular deviation in the first wave
      after ovulation in Nelore (Bos indicus) heifers. Ultrasonographic exams were
      performed and blood samples were collected every 12h from the day of estrus until
      120-144 h after ovulation in seven females. Deviation was defined as the point at
      which the growth rate of the dominant follicle became greater than the growth
      rate of the largest subordinate follicle. Deviation occurred approximately 65 h
      after ovulation. Growth rate of the dominant follicle increased (P<0.05) after
      deviation, while growth rate of the subordinate follicle decreased (P<0.05).
      Diameter of the dominant follicle did not differ from the subordinate follicle at
      deviation (approximately 5.4mm). The dominant follicle (7.6mm) was larger
      (P<0.05) than the subordinate follicle (5.3mm) 96 h after ovulation or 24h after
      deviation. Plasma FSH concentrations did not change significantly during the post
      ovulatory period. The first significant increase in mean plasma progesterone
      concentration occurred on the day of follicular deviation. In conclusion, the
      interval from ovulation to follicular deviation (2.7 days) was similar to that
      previously reported in B. taurus females, but follicles were smaller. Diameters
      of the dominant follicle and subordinate follicle did not differ before deviation
      and deviation was characterized by an increase in dominant follicle and decrease
      in subordinate follicle growth rate. Variations in FSH concentrations within 12-h
      intervals were not involved in follicular deviation in Nelore heifers.

PMID- 16632264
TI  - Dental faculty compensation: have we considered the medical model?

PMID- 16632265
TI  - Bioabsorbable root analogue for closure of oroantral communications after tooth
      extraction: a prospective case-cohort study.
AB  - OBJECTIVE: To assess the clinical capacity of a bioabsorbable root analog to
      close oroantral perforations after extraction. STUDY DESIGN: In this prospective
      case-cohort study, 20 consecutive patients with oroantral communications greater
      than 2 mm were treated with a bioabsorbable root analog (RootReplica). Patients
      were followed up clinically and radiographically for 3 months to monitor the
      healing process. RESULTS: Root replicas could be placed in 14 patients, whereas 6
      patients required the socket to be covered with a buccal sliding flap. In the
      latter cases, fragmentary roots or overly large defects prohibited replica
      fabrication or accurate fitting of the analog, respectively. Healing was
      uneventful in all patients, and epistaxis, swelling, or pain was observed only in
      patients treated with flaps. CONCLUSIONS: The method described is a valuable
      alternative method with which to close oroantral communications but cannot be
      performed in all patients because of technical limitations.

PMID- 16632266
TI  - Expression of interleukin 1-beta, transforming growth factor beta-1, and vascular
      endothelial growth factor in soft tissue over the implant before uncovering.
AB  - BACKGROUND: Overexpression of inflammatory cytokines interleukin 1-beta (IL
      1beta), transforming growth factor beta-1 (TGF-beta1), and vascular endothelial
      growth factor (VEGF) may cause healing impairment following implant insertion,
      jeopardizing success especially in patients previously irradiated. Limited data
      is available regarding expression pattern of inflammatory cytokines in peri
      implant soft tissue caused by the surgical intervention itself. STUDY DESIGN:
      This study examined 21 patients receiving dental implants. Biopsies of peri
      implant tissue were harvested at re-entry 4 months after initial surgery. Eight
      patients underwent probing of untreated mucosa. Three groups were created (group
      1: regular peri-implant mucosa; group 2: patients with irradiated peri-implant
      mucosa, radiation treatment due to oral squamous cell cancer; group 3: control).
      Immunohistochemical staining was performed for TGFss1, IL-1ss, and VEGF. RESULTS:
      Following the placement of dental implants (group 1 vs group 3) a significant
      increase (P > .05) in TGF-beta1, IL-1beta, and VEGF expression in the peri
      implant mucosa was demonstrated. No alteration of this distinct pattern was found
      for previously irradiated tissue (group 1 vs. group 2). CONCLUSIONS: The study
      highlights the fundamental involvement of TGF-beta1, IL-1beta, and VEGF during
      the regeneration of peri-implant soft tissue structures. The use of extended
      interim solutions may be one clinical implication of these prolonged tissue
      remodeling processes.

PMID- 16632267
TI  - Autogenous coronoid process as a new donor source for reconstruction of
      mandibular condyle: an experimental study on goats.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of autogenous coronoid
      process grafts for reconstruction of the mandibular condyle. STUDY DESIGN: Two
      groups of 9 goats each were used. Each animal underwent unilateral total condyle
      and disk removal and was treated by grafting an autogeneous coronoid process. The
      animals in group A were sacrificed at 4, 12, and 24 weeks after surgical
      procedure, and their grafted coronoid processes were harvested for histological
      observation. All animals in group B received 3-dimensional CT scanning
      examination at different times and were sacrificed at 24 weeks after surgical
      procedure. The items of ramus height (RH), transverse dimension of the condyle
      (CT), and posteroanterior dimension of the condyle (CP) were measured for
      comparison with the operated and nonoperated sides. RESULTS: Despite the
      differences in the measurements of RH, CT, and CP between the operated and
      nonoperated sides, the grafted coronoid process had a similar shape and
      histological structures to the normal condyle at 24 weeks after surgical
      procedure. The head of the neocondyle was covered by a cap of fibrous tissue,
      which might play the role of the articular disc. CONCLUSIONS: Under the
      mechanical stimuli of the temporomandibular joint site, the grafted coronoid
      process could gradually remodel to a neocondyle with functional shape and
      structure in goats. This animal study suggests that autogenous coronoid process
      could be considered as a new donor source for reconstruction of the mandibular
      condyle.

PMID- 16632268
TI  - Condylar resorption following temporomandibular joint arthroscopy in a patient
      with essential thrombocythemia.
AB  - Condylar resorption of the temporomandibular joint (TMJ) is a poorly understood
      phenomenon that is the subject of much controversy. The following case report
      depicts a unique case of condylar resorption (CR) in a 49-year-old female patient
      with essential thrombocythemia who underwent arthrocentesis of the TMJ. The exact
      cause of the CR is unclear but it is speculated that it was likely due to
      hemorrhagic and thrombotic complications during surgery secondary to an elevated
      platelet count.

PMID- 16632269
TI  - Prevalence of dental anomalies, ectopic eruption and associated oral
      malformations in subjects with Treacher Collins syndrome.
AB  - OBJECTIVE: To examine the prevalence of dental anomalies in the deciduous and
      permanent teeth, ectopic eruption of permanent first molars, and associated oral
      malformations in individuals with Treacher Collins syndrome. STUDY DESIGN:
      Clinical and radiographic examination of 15 patients with Treacher Collins
      syndrome, from the Hospital for Rehabilitation of Craniofacial Anomalies of the
      University of Sao Paulo, not submitted to orthodontic or orthognathic treatment.
      RESULTS: Dental anomalies were present in 60% of the sample, with 1-8 anomalies
      per individual. Hypoplastic dental anomalies were the most common, followed by
      heterotopic and hyperplastic dental alterations. The most frequent anomalies were
      tooth agenesis (33.3%), mainly affecting the mandibular second premolars, and
      enamel opacities (20% of patients). Ectopic eruption of the maxillary first
      molars was found in 13.3% of subjects. Associated oral malformations, primarily
      isolated cleft palate, followed by complete cleft lip and palate and macrostomia,
      were observed in 66.7% of patients. CONCLUSIONS: Presence of cleft palate
      associated with the syndrome is in agreement with the literature. The high
      prevalence of dental anomalies suggests a possible etiologic relationship, not
      described in the literature so far, between such alterations and the Treacher
      Collins syndrome. Further investigations on larger samples are required to
      confirm these results.

PMID- 16632270
TI  - Evaluation of an oral mandibular advancement titration appliance.
AB  - OBJECTIVES: To determine whether a manually adjustable oral mandibular
      advancement titration appliance (EMA-T) predicts successful long-term treatment
      with an oral mandibular advancement appliance (MAA). STUDY DESIGN: At an academic
      medical center, 21 adults with obstructive sleep apnea (AHI > 10 events/hr)
      performed baseline, titration, and MAA (Klearway) polysomnograms. During the
      titration polysomnogram with EMA-T, the mandible was advanced until apneas and
      hypopneas were eliminated or maximum tolerable advancement was reached.
      Participants then used the MAA at home and, once the mandible was advanced to the
      amount determined during the titration polysomnogram, a polysomnogram with MAA
      was performed. RESULTS: Mean AHI at baseline was 33.5 +/- 18.3 (SD) events/hr.
      During the titration polysomnogram, 9 subjects achieved an AHI < 10 and at least
      a 50% reduction in AHI. None of the subjects met these criteria on the MAA
      polysomnogram. CONCLUSIONS: EMA-T lowered the AHI to efficacious levels in 43% of
      patients but this acute response did not predict the efficacy of long-term MAA
      treatment.

PMID- 16632271
TI  - Oral pityriasis rubra pilaris.
AB  - Pityriasis rubra pilaris is a chronic, papulosquamous dermatosis of unknown
      etiology. Oral mucosal involvement of this condition is rare with only 3
      previously reported cases in the English literature. A case of a 68-year-old man
      with pityriasis rubra pilaris with involvement of tongue and palate is presented.
      Clinical features, histopathologic features, and management of pityriasis rubra
      pilaris are discussed. We hereby present an additional case, the fourth
      worldwide, and review the literature.

PMID- 16632272
TI  - Ulcerative uremic stomatitis associated with untreated chronic renal failure:
      report of a case and review of the literature.
AB  - Uremic stomatitis represents a relatively uncommon intraoral complication seen,
      mostly, in cases of end-stage renal disease or undiagnosed/untreated chronic
      renal failure. Its incidence has decreased due to the advent of renal dialysis.
      Clinically uremic stomatitis is characterized by the presence of painful plaques
      and crusts that are usually distributed on the buccal mucosa, dorsal or ventral
      surface of the tongue, gingiva, lips, and floor of the mouth. Treatment consists
      of improvement of urea blood concentration and the underlying renal failure,
      supported by increased oral hygiene with antiseptic mouthwashes and
      antimicrobial/antifungal agents if necessary. Although uremic stomatitis occurs
      in patients with end-stage renal disease, we report a case of a patient who
      exhibited an ulcerative form of uremic stomatitis related to the sudden relapse
      of uremia, although not in an advanced stage of her renal disease. A description
      of the clinical and microscopic appearance is given along with our hypothesis for
      the pathogenesis of the disease.

PMID- 16632273
TI  - Psammomatoid ossifying fibromas: immunohistochemical analysis and differential
      diagnosis with psammomatous meningiomas of craniofacial bones.
AB  - OBJECTIVE: To clarify the role of immunohistochemistry in the diagnosis of
      psammomatoid ossifying fibroma (PSOF), conventional cemento-ossifying fibroma
      (COF), and psammomatous meningioma (PM) of the craniofacial skeleton. STUDY
      DESIGN: The histology and immunohistochemistry of 4 PSOFs, 6 COFs, and 7 PMs was
      studied. Antibodies included EMA, cytokeratins, smooth muscle actin (SMA),
      desmin, vimentin, CD34, CD10, S-100 protein, and glial fibrillary acidic protein
      (GFAP). RESULTS: All PSOFs showed multiple round ossicles homogeneously
      distributed within a fibroblastic stroma. Psammomatous meningiomas had
      meningothelial features. All tumors, except 1 COF, were positive for EMA. All of
      them expressed vimentin, and none showed cytokeratins. Staining for SMA and S-100
      protein was variable. CD10 was positive in all cases except 2 meningiomas. CD34
      and GFAP stained only 1 case of meningioma each. CONCLUSIONS: The diagnosis of
      PSOF should rest on histologic features. An incorrect diagnosis of meningioma
      based on the expression of EMA should be avoided.

PMID- 16632274
TI  - Enamel dysplasia with odontogenic fibroma-like hamartomas: review of the
      literature and report of a case.
AB  - This article reports on a case presenting with a rare syndrome characterized by
      enamel dysplasia and multiple unerupted teeth with large solid fibrous
      pericoronal lesions manifesting with odontogenic fibroma-like features. Our case
      shows in addition to these findings an anterior open bite malocclusion and
      gingival overgrowths. These overgrowths exhibit the microscopic features of the
      multiple pericoronal odontogenic fibroma-like lesions that appear to be the
      hallmark of this syndrome. This unusual case brings the total number documented
      in the literature to 5, all of which were reported from South Africa.

PMID- 16632275
TI  - Cowden syndrome: report of a case with immunohistochemical analysis and review of
      the literature.
AB  - Cowden syndrome is a rare condition defined by multiple hamartomatous growths and
      a guarded prognosis owing to the high risk of cancer development. The syndrome is
      inherited as an autosomal dominant trait with incomplete penetrance and variable
      expressivity. The PTEN/MMAC1/TEP1 tumor suppressor gene on chromosome 10q23.3,
      has proven to contain a germline mutation predisposing for uncontrolled cell
      growth and survival via the PI3K/AKT pathway. Presented here is a case of Cowden
      syndrome in a patient with multiple hamartomas of the nose, midfacial skin and
      oral mucosa, and fissured tongue; plus a history of bipolar disease, iron
      deficiency anemia, basal cell carcinoma, fibroids of the uterus, and arthritis.
      The family history was significant for a daughter diagnosed with lung cancer. A
      final diagnosis of Cowden syndrome was made on the basis of established criteria
      and confirmed using immunohistochemistry directed against PTEN and phosphorylated
      AKT.

PMID- 16632276
TI  - The oral manifestations of Maroteaux-Lamy syndrome (mucopolysaccharidosis VI): a
      case report.
AB  - Maroteaux-Lamy syndrome is one of the genetic disorders involving disturbances in
      mucopolysaccharide metabolism resulting in increased storage of acid
      mucopolysaccharide in various tissues. The basic defect in Maroteaux-Lamy
      syndrome is a deficiency of arylsulfatase B, which leads to accumulation of
      dermatan sulfate in tissues and their urinary excretion. The deposition of
      mucopolysaccharides leads to a progressive disorder involving multiple organs
      that often results in death in the second decade of life. This disease, which has
      several oral and dental manifestations, is first diagnosed on the basis of
      clinical findings. A large head, short neck, corneal opacity, open mouth
      associated with an enlarged tongue, enlargement of skull, and a long antero
      posterior dimension are the main characteristic features. Dental complications
      can be severe and include unerupted dentition, dentigerous cystlike follicles,
      malocclusions, condylar defects, and gingival hyperplasia. An 11-year-old boy
      with Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is described in this
      article, with special emphasis on the oral manifestations.

PMID- 16632277
TI  - Ameloblastic carcinoma of the mandible resembling odontogenic cyst in a panoramic
      radiograph.
AB  - Ameloblastic carcinoma is a rare odontogenic tumor exhibiting histologic evidence
      of malignancy in the primary or recurrent tumor, regardless of whether it has
      metastasized or not. Most ameloblastic carcinomas are presumed to have arisen de
      novo, with few cases of malignant transformation of ameloblastoma being apparent.
      A case is reported of a 21-year-old caucasian female with ameloblastic carcinoma
      in the left angulus area of the mandible resembling an odontogenic cyst in the
      panoramic radiograph. In addition to the panoramic radiograph, computerized
      tomography (CT) and magnetic resonance (MR) images were taken preoperatively.
      This report demonstrates that CT or MR examinations may be crucial in
      differentiating odontogenic tumors from cysts.

PMID- 16632278
TI  - Subjective image quality of digitally filtered radiographs acquired by the Durr
      Vistascan system compared with conventional radiographs.
AB  - OBJECTIVES: To compare the different digital filters implemented in the Durr
      Vistascan system with conventional film and to analyze the filter specificity to
      anatomic structures. STUDY DESIGN: Ten panoramic image pairs and 10 periapical
      image pairs (1 digital and 1 conventional) were obtained from 20 patients
      conventionally and digitally. The display quality of different anatomic image
      structures was rated subjectively on a 5-point scale. The responses were
      evaluated using ANOVA and Tukey-Kramer post hoc tests. The intraobserver
      reliability was evaluated by Cohen's kappa statistics. RESULTS: The display
      quality of anatomic structures was rated higher by using Caries 1 or 2 filters
      for periapical and Periodontal 1 or 2 filters for panoramic images, whereas
      nonfiltered and Noise Reduction-filtered images received the lowest scorings
      compared to all other digital image modalities (P < or = .0097). The superiority
      of conventional radiographs to the digital ones was statistically significant (P
      < or = .0039 and P < or = .0152 respectively). CONCLUSIONS: Depending on the
      diagnostic task, digital images of the Vistascan system should be filtered before
      examination. Perfect conventional radiographs still remain the gold standard for
      image quality.

PMID- 16632279
TI  - Image artifact in dental cone-beam CT.
AB  - PURPOSE: The purpose of this study was to investigate the appearance and possible
      cause of an artifact seen in limited-volume cone-beam CT imaging. METHODS: A
      water-filled plastic cylinder was used as a phantom of the head. A test object
      was constructed as a bone-equivalent phantom to be imaged. The test object was
      variously positioned at the center of the phantom and near its margins. CT images
      of the test object were acquired using a 3DX Accuitomo system. RESULTS: In slice
      images with the test object positioned near the margin of the phantom, arch
      shaped defects or deformities were observed on the side of the object. There was
      a negative correlation between the artifact and the CT value of the object. The
      artifact was larger in images scanned with a higher voltage. CONCLUSION: The
      probability that this artifact is caused by halation from the image intensifier
      (II) system is suggested.

PMID- 16632280
TI  - Prevalence of infraorbital ethmoid (Haller's) cells on panoramic radiographs.
AB  - OBJECTIVE: To determine the prevalence of infraorbital ethmoid cells on panoramic
      radiographs. Infraorbital ethmoid (Haller's) cells are extensions of ethmoid air
      cells into the areas of the orbit and maxillary sinus and may be seen when
      present on panoramic radiographs. STUDY DESIGN: In this retrospective study, 233
      panoramic radiographs were examined for infraorbital ethmoid cells. A diagnostic
      criterion was developed to identify infraorbital ethmoid cells on panoramic
      radiographs. RESULTS: Sixty panoramic radiographs were discarded because the
      orbital outline was not seen. Of the 173 panoramic radiographs, the prevalence of
      infraorbital ethmoid cells was 38.2% (30.8% for men and 40.3% for women).
      CONCLUSIONS: The prevalence on panoramic radiographs was within the range of
      prevalence on CT examinations reported by others.

PMID- 16632281
TI  - A 1-year follow-up study on leakage of single-cone fillings with RoekoRSA sealer.
AB  - OBJECTIVE: The aim of this study was to measure long-term leakage along single
      cone (SC) fillings. STUDY DESIGN: Two groups of canines (n = 30) were prepared
      and a size 55 file was the apical master file. Step-back was performed using
      files of sizes 60, 70, and 80. The canals were filled by the single cone
      technique using RoekoRSA as sealer. To place sealer into each canal, a
      bidirectional spiral was used in 1 group, whereas a gutta-percha cone was used in
      the other group. Immediately after root filling, the coronal portion of root
      filling was removed by postspace preparation. Leakage along the 4 mm remaining
      apical root filling was measured after 1 week and again after 1 year using a
      fluid transport model. Ten additional canine roots were prepared and filled with
      gutta-percha cones without sealer, serving as positive controls. Occurrence of
      apical extrusion of materials was recorded. RESULTS: The apical root filling in
      all 60 canine roots did not show leakage either at 1 week or at 1 year. All 10
      positive controls showed gross leakage (>20 muL/h). In no case gutta-percha
      extruded through the apical foramen. Sealer extruded apically in 88% of the roots
      where a gutta-percha cone was used to introduce sealer, whereas in 28% of the
      roots where a bidirectional spiral was used to introduce sealer (by chi-square
      test, P < .05). CONCLUSION: In wide and straight canals, SC fillings with
      RoekoRSA sealer prevented fluid transport for 1 year. Using bidirectional spiral
      to place sealer reduced sealer extrusion under the conditions of this experiment.

PMID- 16632282
TI  - Three-dimensional visualization of a mandibular first molar with three distal
      roots using computer-aided rapid prototyping.
AB  - Nonsurgical endodontic therapy of a right mandibular first molar with 3 distal
      roots was successfully performed with the aid of magnification. 3D data (DICOM
      format) of the tooth were obtained from a CT HighSpeed Advantage and a Denta Scan
      program produced by GE Medical Systems. The CT protocol used for this procedure
      involved a slit thickness of 1 mm. The 3D digital data obtained were fed into a
      visualization program (V-works; Cybermed Co) and then exported to the rapid
      prototyping machine for fabrication of the actual-sized tooth model. The material
      for the model-making process was starch. The 3D digital visualization and the
      computer-aided rapid prototyping (CARP) model clearly showed 3 separate distal
      roots (distobuccal, distolingual, and middle distal). The CARP technique seems to
      be a useful imaging technology to document unusual root anatomy in clinical
      dentistry.

PMID- 16632283
TI  - Influence of simulated clinical use on the torsional behavior of nickel-titanium
      rotary endodontic instruments.
AB  - OBJECTIVE: The aim of this study was to assess the influence of cyclic
      deformation up to one half and three quarters of the fatigue life of NiTi rotary
      endodontic instruments on their behavior in torsion. STUDY DESIGN: Thirty sets of
      0.04 and 0.06 ProFile instruments in sizes #20, #25, and #30 were randomly
      divided into 3 groups: 1 contained 10 sets of new files, torsion tested to
      failure, while the other 2 groups, with 10 sets each, were first submitted to
      fatigue tests of up to one half and three fourths of their fatigue life,
      respectively, in geometrical conditions similar to those of the clinical practice
      and then torsion tested for rupture. RESULTS: Statistical analysis of the values
      obtained for the torque to failure and maximum angular deflection, using the
      Student t test at the 95% confidence level, showed that the cyclic deformation of
      instruments of up to one half and three fourths of their fatigue life gives rise
      to a significant reduction in these parameters. CONCLUSIONS: The simulated
      clinical use of ProFile instruments for shaping curved canals adversely affects
      their torsional properties.

PMID- 16632284
TI  - Increased number of anaerobic bacteria in the infected root canal in type 2
      diabetic rats.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      type 2 diabetes mellitus and anaerobic bacteria detected in infected root canals.
      STUDY DESIGN: Normal Wistar rats (control) received a standard laboratory diet
      with water (group A), and GK rats (type 2 diabetes mellitus rats) a normal
      laboratory diet with water (group B) or a 30% sucrose solution (group C).
      Chemotaxis assay was conducted on polymorphonuclear leukocytes from the 3 groups,
      and the numbers of anaerobic bacteria in infected root canals were determined.
      RESULTS: In the chemotaxis assay on the polymorphonuclear leukocytes, the
      chemotactic response of cells in group C was lower than that for groups A and B
      (P < .01). As to bacteria detected in the root canal, obligate anaerobic bacteria
      which stained gram negative, were significantly more numerous in group C (P <
      .01) than in groups A and B. CONCLUSION: The metabolic condition produced by type
      2 diabetes mellitus in rats might lower the general host resistance against
      bacterial infection.

PMID- 16632285
TI  - A novel chitosan oligosaccharide-stearic acid micelles for gene delivery:
      properties and in vitro transfection studies.
AB  - Stearic acid (SA) grafted chitosan oligosaccharide (CSO) (CSO-SA), which was
      synthesized by an 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated
      coupling reaction, was demonstrated to form micelle like structure by self
      aggregation in aqueous solution. The critical micelle concentration (CMC) of CSO
      SA with 15.4% amino substituted degree of CSO was about 0.035 mg/ml. The micelles
      with 1mg/ml CSO-SA concentration had 70.6 nm volume average hydrodynamic diameter
      with a narrow size distribution and 46.4+/-0.1 mV surface potential. Due to the
      cationic property, the micelles could compact the plasmid DNA to form micelle/DNA
      complexes nanoparticles, which can efficiently protect the condensed DNA from
      enzymatic degradation by DNase I. The volume average hydrodynamic diameter of CSO
      SA micelle/DNA complex increased from 203 nm to 318 nm and decreased to 102 nm
      due to the variation of zeta potential when the N/P ratio increased from 0.25 to
      3.6 and from 3.6 to 58. The IC(50) value of the CSO-SA micelle against A549 cells
      was 543.16 microg/ml, while the IC(50) of Lipofectamine 2000 was about 6
      microg/ml. The in vitro transfection efficiency of CSO-SA micelles was
      investigated by using plasmid DNA (pEGFP-C1). The transfection efficiency with
      CSO-SA/DNA (N/P ratio is 29) was increased with the post-transfection time (in
      76h), while the optimal transfection of Lipofectamine 2000/DNA was obtained at
      24h. The transfection of CSO-SA was not interfered in the presence of 10% fetal
      bovine serum, which showed remarkable enhancement effect. The optimal
      transfection efficiency of CSO-SA micelles in A549 cells was about 15%, which was
      higher than that of CSO (about 2%) and approach to that of Lipofectamine 2000
      (about 20%). The low cytotoxic biodegradable CSO-SA micelles could be used as an
      effective DNA condensation carrier for gene delivery system.

PMID- 16632286
TI  - Sodium salicylate reduces inhibitory postsynaptic currents in neurons of rat
      auditory cortex.
AB  - Sodium salicylate (SS) is a medicine for anti-inflammation and for chronic pain
      relief with a side effect of tinnitus. To understand the cellular mechanisms of
      tinnitus induced by SS in the central auditory system, we examined effects of SS
      on evoked and miniature inhibitory postsynaptic currents (eIPSCs and mIPSCs)
      recorded from layer II/III pyramidal neurons of rat auditory cortex in a brain
      slice preparation with whole-cell patch-clamp techniques. Both eIPSCs and mIPSCs
      recorded from the auditory cortex could be completely blocked by bicuculline, a
      selective GABA(A) receptor antagonist. SS did not change the input resistance of
      neurons but was found to reversibly depress eIPSCs in a concentration-dependent
      manner. SS reduced eIPSCs to 82.3% of the control level at 0.5 mM (n=7) and to
      60.9% at 1.4 mM (n=12). In addition, SS at 1.4 mM significantly reduced the
      amplitude of mIPSCs from 24.12+/-1.44 pA to 19.92+/-1.31 pA and reduced the
      frequency of mIPSCs from 1.34+/-0.23 Hz to 0.89+/-0.13 Hz (n=6). Our results
      demonstrate that SS attenuates inhibitory postsynaptic currents in the auditory
      cortex, suggesting that the alteration of inhibitory neural circuits may be one
      of the cellular mechanisms for tinnitus induced by SS in the central auditory
      region.

PMID- 16632287
TI  - Application of plant DNA markers in forensic botany: genetic comparison of
      Quercus evidence leaves to crime scene trees using microsatellites.
AB  - As highly polymorphic DNA markers become increasingly available for a wide range
      of plant and animal species, there will be increasing opportunities for
      applications to forensic investigations. To date, however, relatively few studies
      have reported using DNA profiles of non-human species to place suspects at or
      near crime scenes. Here we describe an investigation of a double homicide of a
      female and her near-term fetus. Leaf material taken from a suspect's vehicle was
      identified to be that of sand live oak, Quercus geminata, the same tree species
      that occurred near a shallow grave where the victims were found. Quercus-specific
      DNA microsatellites were used to genotype both dried and fresh material from
      trees located near the burial site and from the material taken from the suspect's
      car. Samples from the local population of Q. geminata were also collected and
      genotyped in order to demonstrate that genetic variation at four microsatellite
      loci was sufficient to assign leaves to an individual tree with high statistical
      certainty. The cumulative average probability of identity for these four loci was
      2.06x10(-6). DNA was successfully obtained from the dried leaf material although
      PCR amplification was more difficult than amplification of DNA from fresh leaves.
      The DNA profiles of the dried leaves from the suspect's car did not match those
      of the trees near the crime scene. Although this investigation did not provide
      evidence that could be used against the suspect, it does demonstrate the
      potential for plant microsatellite markers providing physical evidence that links
      plant materials to live plants at or near crime scenes.

PMID- 16632288
TI  - Episodic receptive aphasia in a child with Landau-Kleffner Syndrome: PET
      correlates.
AB  - We report a four-year-old boy with Landau-Kleffner Syndrome (LKS) characterized
      by episodic receptive aphasia lasting for few weeks followed by gradual recovery
      of baseline language functions. Neuropsychological evaluation during an episode
      showed severe impairment in verbal skills and comprehension, but relative
      preservation of non-verbal skills. Although he could carry on a conversation
      during remission, neuropsychological evaluation demonstrated findings reflective
      of receptive language deficits. Prolonged EEG disclosed frequent sharp-wave
      activity in the left and right temporal regions but no electrographic seizures.
      Glucose metabolism PET scan during the fourth episode of aphasia revealed intense
      hypermetabolism in the left temporal neocortex. Awake EEG during the PET tracer
      uptake period showed 6.0 spikes/min in the left temporal region and 4.0
      spikes/min in the right. A repeat PET scan during remission showed hypometabolism
      in the left temporal cortex. Awake EEG during the FDG uptake period showed 16.0
      spikes/min in the right temporal region and 0.3 spikes/min in the left. During
      his fifth aphasic episode, EEG (without PET) showed 0.16 spikes/min in the right
      temporal region and none in the left. Intermittent short episodes of
      predominantly receptive aphasia with near-total recovery between episodes can be
      one of the clinical presentations of LKS. This case illustrates the dynamic
      changes of glucose metabolism in the temporal lobe during episodes of aphasia and
      remission in a case with LKS. The clinical course of our patient with transient
      EEG and PET findings suggest that glucose metabolism in LKS cannot be attributed
      solely to interictal epileptiform activities on scalp EEG.

PMID- 16632289
TI  - Steroid therapy in an infant with human herpesvirus 6 encephalopathy.
AB  - We describe a 10-month-old girl who developed convulsive status during febrile
      illness. Human herpesvirus 6 DNA was detected in both the serum and the
      cerebrospinal fluid by polymerase chain reaction. Interleukin-6 was increased in
      the serum. The patient improved after a commencement of steroids pulse therapy.
      This case suggests that proinflammatory cytokines are responsible for the
      pathogenesis of the encephalopathy.

PMID- 16632290
TI  - Images in sleep medicine: introduction.

PMID- 16632291
TI  - Age-associated changes in CD90 expression on thymocytes and in TCR-dependent
      stages of thymocyte maturation in male rats.
AB  - To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old
      rats, we analysed the expression of: (i) CD4/CD8/TCRalphabeta and (ii) Thy-1,
      which is supposed to be a regulator of TCRalphabeta signalling, and thereby the
      thymocyte selection thresholds. Since an essential role for TCRalphabeta
      signalling in the development of CD4+25+T(reg)-cells was suggested, the frequency
      of these cells was also quantified. We demonstrated that, as for mice, early
      thymocyte differentiational steps within the CD4-8- double negative (DN)
      developmental stage are age-sensitive. Furthermore, we revealed that TCRalphabeta
      dependent stages of T-cell development are affected by ageing, most likely due to
      an impaired expression of Thy-1 on TCRalphabeta(low) thymocytes entering
      selection processes. The diminished frequency of the post-selection CD4+8+ double
      positive (DP) cells in aged rats, together with an overrepresentation of mature
      single positive (SP) cells, most probably suggests more efficient
      differentiational transition from the DP TCRalphabeta(high) to the SP
      TCRalphabeta(high) developmental stage, which is followed by an increase in pre
      migration proliferation of the mature SP cells. Moreover, the study indicated
      impaired intrathymic generation of CD4+25+T(reg)-cells in aged rats, thus
      providing a possible explanation for the increased frequency of autoimmune
      diseases in ageing.

PMID- 16632292
TI  - Mitochondrial DNA deletions and the aging heart.
AB  - Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum
      of human disorders and proposed to be a potential contributor of aging. However,
      in an age-dependent increase of the common 4977 bp deletion of human mtDNA still
      many unanswered questions remain. Comparing mtDNA copy levels in different
      tissues revealed that cardiac muscle had the highest, while the cortex cerebelli
      showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy
      number showed no changes during aging. In heart tissue, the amount of 4977 bp
      mtDNA deletion increased in an age-dependent manner showing significant
      differences at the age of 40 years and older (p<0.005). In vitro studies
      analyzing human normal cells transfected with telomerase (BJ-T) revealed that
      oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp
      deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis.
      Interestingly, OS induced apoptosis only in transformed human fibroblasts by
      activation of the intrinsic (mitochondrial-mediated) signalling pathway as
      indicated by morphological damage of mitochondria, DNA laddering and increase of
      the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp
      deletion increased in an age-dependent manner and it was more detectable after
      the 4th decade of life, although there was some scatter in the data. Since,
      apoptosis was induced by the mitochondria-mediated pathway only in transformed
      cells, the role for apoptosis in normal tissue of the aging heart remains
      unclear.

PMID- 16632293
TI  - The value of the abdominal radiograph in children with functional
      gastrointestinal disorders.
AB  - Functional gastrointestinal disorder is a common problem in childhood. The
      symptoms vary from a relative mild gastrointestinal problem such as abdominal
      pain or infrequent defecation to severe problems with fecal impaction and fecal
      incontinence. The aim of this review is to describe and evaluate the value of the
      different existing methods to assess fecal loading on an abdominal radiograph
      with or without the use of radio-opaque markers in the diagnosis of functional
      abdominal pain, functional constipation and functional non-retentive fecal
      incontinence. In our opinion, the abdominal radiograph has limited value in the
      diagnostic work-up of children with functional gastrointestinal disorders.

PMID- 16632294
TI  - Capillary gas chromatographic determination of phenylpropanolamine in
      pharmaceutical preparation.
AB  - Analytical procedure has been developed for the gas chromatographic determination
      of phenylpropanolamine (PPA) using trifluoroacetylacetone (FAA) as derivatizing
      reagent. Elution is carried out from the column HP-5 (30 mx0.32 mm i.d.) with
      film thickness 0.25 microm at initial column temperature 70 degrees C for 5 min,
      followed by heating rate 10 degrees C/min up to 120 degrees C. Injection port
      temperature was maintained at 270 degrees C. Nitrogen flow rate was 2 ml/min and
      detection was by FID. The linear calibration curve was obtained with 30-150
      microg/ml PPA with detection limit of 6.0 microg/ml. The method was used for the
      determination of PPA from Sinutab and Tavegyl-D tablets. The relative standard
      deviation (R.S.D.) for the analysis of pharmaceutical preparation was obtained
      within 0.4-0.9%.

PMID- 16632295
TI  - [Neuroimaging findings in eclamptic patients still symptomatic after 24 hours: a
      descriptive study about 19 cases].
AB  - OBJECTIVE: To describe the neuroimaging findings in eclamptic patients still
      symptomatic after 24 hours. PATIENTS AND METHODS: All parturients consecutively
      admitted over a 12-month period for eclampsia and presenting with neurological
      disorders (coma, focal neurological abnormalities, and eye sight disturbance)
      underwent cerebral CT-scan and/or MRI. RESULTS: Nineteen women were studied, and
      all had abnormal neuroradiological findings. The CT-scan was normal in three
      cases. Cerebral oedema was the predominant lesion (14 cases). It was localized in
      the parietal or occipital area (12 cases), paraventricular area (1 case), or was
      diffuse (1 case). Diffusion weighted MRI was performed in four cases and showed
      cytotoxic cerebral oedema in one case. There were three cases of cerebral venous
      thrombosis and two cases of intracerebral haemorrhage. CONCLUSION: Various
      neuroradiological lesions can be observed in eclamptic patients. A localized
      cerebral oedema is the most frequent. Diffusion weighted MRI should be
      systematically done when neurological disorders persist.

PMID- 16632296
TI  - [Anaesthetic considerations for interventional radiology].
AB  - OBJECTIVE: To describe the new procedures applied for interventional radiology
      leading to specific anaesthetic care and organization. DATA SOURCE: Record of
      references from national and international journals in Medline. STUDY SELECTION:
      All types of articles were selected including prospective studies, practice
      guidelines, reviews and case reports. DATA SYNTHESIS: During interventional
      radiology, anaesthesia should be adapted to the duration of the procedure, the
      pain induced by the radiologist, the position of the patient and its medical
      status. General anaesthesia would be preferred for long procedures, requiring
      total immobility. Locoregional anaesthesia can be proposed for some cases.
      Sedation associating hypnotics (propofol, midazolam, sevoflurane) and opioids
      (alfentanil, remifentanil) is commonly used according to different schemes, as
      discontinuous boluses, continuous infusion, target controlled intravenous
      sedation or patient controlled sedation. Monitoring of temperature and diuresis
      may be useful for long procedures. Haemodynamic monitoring (arterial catheter,
      central venous pressure) and haemostatic monitoring may be necessary for
      interventional neuroradiology and endovascular stenting. Radiofrequency and laser
      procedures are often painful, requiring the choice of adequate analgesic regimen.
      Hydratation associated with acetylcysteine seems to be able to prevent contrast
      induced nephropathy in patients with risk factors for chronic renal
      insufficiency. CONCLUSION: As advances in interventional radiology are obvious,
      general organisation as well as anaesthetic procedures should be adapted to these
      specific techniques.

PMID- 16632297
TI  - Effect of zinc replacement on lipids and lipoproteins in type 2-diabetic
      patients.
AB  - Abnormal zinc and lipid plasma levels occur more frequently in metabolically
      uncontrolled diabetic patients. These lipid alterations are key factors in the
      emergence of microvascular complications, which lead to death in those patients.
      Yet, zinc sulfate supplementation may be a therapeutical resource to recover some
      functioning and improve life span. This article reports the assessment of lipid
      profile from type 2-diabetes mellitus patients treated with hypoglycemic therapy
      drugs, who additionally presented zinc levels lower than average in Mexican
      reference. The patients received a 100 mg zinc sulfate treatment in a crossover
      double-blind design of clinically controlled study with starch as placebo. The
      diabetic patients had changes in their lipid profile after a 12-week zinc
      treatment as compared with placebo treatment. The 100 mg zinc sulfate treatment
      was well tolerated, significantly reduced total cholesterol and triglyceride
      concentrations, and increased those corresponding to zinc as well as HDL
      cholesterol in the bloodstream. Thus, using this treatment the cardiovascular
      involvement is expected to decrease in the type 2-diabetes mellitus patients,
      especially those with myocardial infarction and stroke, which are the main death
      causes in Mexico.

PMID- 16632298
TI  - Prolactin synthesis by lymphocytes from patients with systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of
      the skin and internal organs. It has been demonstrated that serum prolactin
      levels are increased in patients with various connective tissue diseases. The aim
      of this study was to investigate the possible source of excessive prolactin
      synthesis in SSc and its effects on immune cells. The study group consisted of 52
      patients with diffuse SSc (44 women and eight men) and 52 age and sex matched
      healthy controls. The methods used were: ELISA and indirect immunofluorescence.
      Our results show significantly elevated level of prolactin in male and female
      patients with SSc and increased prolactin production by SSc lymphocytes as
      compared to healthy donors X lymphocytes (25.4+/-11.0 vs. 13.4+/-5.0 absorbance
      units). Patients X and healthy controls X lymphocytes, showed equal presence of
      prolactin receptors. Soluble interleukin 2 receptor (CD25) concentration, was
      significantly higher in supernatants of prolactin stimulated lymphocytes, as
      compared to non-stimulated lymphocytes. We conclude that lymphocytes might
      contribute to elevated prolactin levels in patients with SSc and that these cells
      themselves may be sensitive to prolactin stimulation. Therefore, a pharmacologic
      attempt to lower prolactin levels in patients with SSc could proof beneficial.

PMID- 16632299
TI  - The trials and tribulations of Tysabri.

PMID- 16632300
TI  - Of mice and men ... and vCJD.

PMID- 16632301
TI  - The return of natalizumab: weighing benefit against risk.

PMID- 16632302
TI  - Good clinical practice in neurorehabilitation.

PMID- 16632303
TI  - Anticholinergic drugs and elderly people: a no brainer?

PMID- 16632304
TI  - Treatment of drug resistance in epilepsy: one step at a time.

PMID- 16632305
TI  - Assisted living at the end of life.

PMID- 16632306
TI  - To the point: acupuncture and migraine.

PMID- 16632309
TI  - Predicting susceptibility and incubation time of human-to-human transmission of
      vCJD.
AB  - BACKGROUND: Identification of possible transmission of variant Creutzfeldt-Jakob
      disease (vCJD) via blood transfusion has caused concern over spread of the
      disease within the human population. We aimed to model iatrogenic spread to
      enable a comparison of transmission efficiencies of vCJD and bovine spongiform
      encephalopathy (BSE) and an assessment of the effect of the codon-129
      polymorphism on human susceptibility. METHODS: Mice were produced to express
      human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene.
      Since the human PrP gene has variation at codon 129, with MM, VV, and MV
      genotypes, three inbred lines with an identical genetic background were produced
      to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were
      inoculated with BSE or vCJD and assessed for clinical and pathological signs of
      disease. FINDINGS: BSE was transmitted to the bovine line but did not transmit to
      the human lines. By contrast, vCJD was transmitted to all three human lines with
      different pathological characteristics for each genotype and a gradation of
      transmission efficiency from MM to MV to VV. INTERPRETATION: Transmission of BSE
      to human beings is probably restricted by the presence of a significant species
      barrier. However, there seems to be a substantially reduced barrier for human-to
      human transmission of vCJD. Moreover, all individuals, irrespective of codon-129
      genotype, could be susceptible to secondary transmission of vCJD through routes
      such as blood transfusion. A lengthy preclinical disease is predicted by these
      models, which may represent a risk for further disease transmission and thus a
      significant public-health issue.

PMID- 16632310
TI  - Rapid detection of major depression in epilepsy: a multicentre study.
AB  - BACKGROUND: Depression is a common comorbid disorder in epilepsy but is not
      routinely assessed in neurology clinics. We aimed to create a rapid yet accurate
      screening instrument for major depression in people with epilepsy. METHODS: We
      developed a set of 46 items to identify symptoms of depression that do not
      overlap with common comorbid cognitive deficits or adverse effects of
      antiepileptic drugs. This preliminary instrument and several reliable and valid
      instruments for diagnosis of depression on the basis of criteria from the
      Diagnostic and Statistical Manual IV, depression symptom severity, health status,
      and toxic effects of medication were applied to 205 adult outpatients with
      epilepsy. We used discriminant function analysis to identify the most efficient
      set of items for classification of major depression, which we termed the
      neurological disorders depression inventory for epilepsy (NDDI-E). Baseline data
      for 229 demographically similar patients enrolled in two other clinical studies
      were used for verification of the original observations. FINDINGS: The
      discriminant function model for the NDDI-E included six items. Internal
      consistency reliability of the NDDI-E was 0.85 and test-retest reliability was
      0.78. An NDDI-E score of more than 15 had a specificity of 90%, sensitivity of
      81%, and positive predictive value of 0.62 for a diagnosis of major depression.
      Logistic regression showed that the model of association of major depression and
      the NDDI-E was not affected by adverse effects of antiepileptic medication,
      whereas models for depression and generic screening instruments were. The
      severity of depression symptoms and toxic effects of drugs independently
      correlated with subjective health status, explaining 72% of variance. Results
      from a separate verification sample also showed optimum sensitivity, specificity,
      and predictive power at a cut score of more than 15. INTERPRETATION: Major
      depression in people with epilepsy can be identified by a brief set of symptoms
      that can be differentiated from common adverse effects of antiepileptic drugs.
      The NDDI-E could enable rapid detection and improve management of depression in
      epilepsy in accordance with internationally recognised guidelines.

PMID- 16632311
TI  - The effect of social networks on the relation between Alzheimer's disease
      pathology and level of cognitive function in old people: a longitudinal cohort
      study.
AB  - BACKGROUND: Few data are available about how social networks reduce the risk of
      cognitive impairment in old age. We aimed to measure this effect using data from
      a large, longitudinal, epidemiological clinicopathological study. METHODS: 89
      elderly people without known dementia participating in the Rush Memory and Aging
      Project underwent annual clinical evaluation. Brain autopsy was done at the time
      of death. Social network data were obtained by structured interview. Cognitive
      function tests were Z scored and averaged to yield a global and specific measure
      of cognitive function. Alzheimer's disease pathology was quantified as a global
      measure based on modified Bielschowsky silver stain. Amyloid load and the density
      of paired helical filament tau tangles were also quantified with antibody
      specific immunostains. We used linear regression to examine the relation of
      disease pathology scores and social networks to level of cognitive function.
      FINDINGS: Cognitive function was inversely related to all measures of disease
      pathology, indicating lower function at more severe levels of pathology. Social
      network size modified the association between pathology and cognitive function
      (parameter estimate 0.097, SE 0.039, p=0.016, R(2)=0.295). Even at more severe
      levels of global disease pathology, cognitive function remained higher for
      participants with larger network sizes. A similar modifying association was
      observed with tangles (parameter estimate 0.011, SE 0.003, p=0.001, R(2)=0.454).
      These modifying effects were most pronounced for semantic memory and working
      memory. Amyloid load did not modify the relation between pathology and network
      size. The results were unchanged after controlling for cognitive, physical, and
      social activities, depressive symptoms, or number of chronic diseases.
      INTERPRETATION: These findings suggest that social networks modify the relation
      of some measures of Alzheimer's disease pathology to level of cognitive function.

PMID- 16632312
TI  - Vanishing white matter disease.
AB  - Vanishing white matter disease (VWM) is one of the most prevalent inherited
      childhood leucoencephalopathies. The classical phenotype is characterised by
      early childhood onset of chronic neurological deterioration, dominated by
      cerebellar ataxia. VWM is unusual because of its clinically evident sensitivity
      to febrile infections, minor head trauma, and acute fright, which may cause rapid
      neurological deterioration and unexplained coma. Most patients die a few years
      after onset. The phenotypic variation is extremely wide, including antenatal
      onset and early demise and adult-onset, slowly progressive disease. MRI findings
      are diagnostic in almost all patients and are indicative of vanishing of the
      cerebral white matter. The basic defect of this striking disease resides in
      either one of the five subunits of eukaryotic translation initiation factor
      eIF2B. eIF2B is essential in all cells of the body for protein synthesis and its
      regulation under different stress conditions. Although the defect is in
      housekeeping genes, oligodendrocytes and astrocytes are predominantly affected,
      whereas other cell types are surprisingly spared. Recently, undue activation of
      the unfolded-protein response has emerged as important in the pathophysiology of
      VWM, but the selective vulnerability of glia for defects in eIF2B is poorly
      understood.

PMID- 16632313
TI  - Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases.
AB  - Rapid-eye-movement (REM) sleep behaviour disorder (RBD) is characterised by loss
      of muscular atonia and prominent motor behaviours during REM sleep. RBD can cause
      sleep disruption and severe injuries for the patient or bed partner. The disorder
      is strongly associated with neurodegenerative diseases, such as multiple-system
      atrophy, Parkinson's disease, dementia with Lewy bodies, and progressive
      supranuclear palsy. In many cases, the symptoms of RBD precede other symptoms of
      these neurodegenerative disorders by several years. Furthermore, several recent
      studies have shown that RBD is associated with abnormalities of
      electroencephalographic activity, cerebral blood flow, and cognitive, perceptual,
      and autonomic functions. RBD might be a stage in the development of
      neurodegenerative disorders and increased awareness of this could lead to
      substantial advances in knowledge of mechanisms, diagnosis, and treatment of
      neurodegenerative disorders.

PMID- 16632314
TI  - Idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension is common in obese women and can lead to
      significant visual impairment. First described more than 100 years ago, the cause
      of the disorder remains unknown. Despite a multitude of proposed links, the
      aetiology has never been established. Impairment of cerebrospinal-fluid
      reabsorption is the most likely underlying pathophysiological cause of the raised
      pressure, but this notion has yet to be proven. Cerebral venous sinus
      abnormalities associated with the disorder need further exploration. Although the
      major symptoms of headache and visual disturbance are well documented, most data
      for disease outcome have been from small retrospective case series. No randomised
      controlled trials of treatment have been done and the management is
      controversial. The importance of weight loss needs clarification, the role of
      diuretics is uncertain, and which surgical intervention is the most effective and
      safe is unknown. Prospective trials to examine these issues are urgently needed.

PMID- 16632315
TI  - Neoplastic meningitis.
AB  - Neoplastic meningitis is a complication of the CNS that occurs in 3-5% of
      patients with cancer and is characterised by multifocal neurological signs and
      symptoms. Diagnosis is problematic because the disease is commonly the result of
      pleomorphic manifestations of neoplastic meningitis and co-occurrence of disease
      at other sites. Useful tests to establish diagnosis and guide treatment include
      MRI of the brain and spine, cerebrospinal fluid (CSF) cytology, and radioisotope
      CSF flow studies. Assessment of the extent of disease of the CNS is of value
      because large-volume subarachnoid disease or CSF flow obstruction is
      prognostically significant. Radiotherapy is an established and beneficial
      treatment for patients with neoplastic meningitis with large tumour volume
      including parenchymal brain metastasis, sites of symptomatic disease, or CSF flow
      block. Because neoplastic meningitis affects the entire neuraxis, chemotherapy
      treatment can include intra-CSF fluid (either intraventricular or intralumbar) or
      systemic therapy. Most patients (>70%) with neoplastic meningitis have
      progressive systemic disease and consequently treatment is palliative and tumour
      response is of restricted durability. Furthermore, as there is no compelling
      evidence of a survival advantage with aggressive multimodal treatment, future
      trials need be done to determine the effect of treatment on quality of life and
      control of neurological symptoms.

PMID- 16632316
TI  - Olfactory ensheathing cells: ripples of an incoming tide?
AB  - Until now, brain and spinal cord injuries that sever nerve fibres have resulted
      in a degree of incurable functional loss. An incoming tide of research is now
      beginning to challenge this as yet unbreached sea wall. One of the most promising
      approaches involves a recently discovered type of cell, the olfactory ensheathing
      cell, which can be obtained from the adult nasal lining. In animal models
      transplantation of cultured olfactory ensheathing cells into an injured spinal
      cord induces regeneration, remyelination of severed spinal nerve fibres, and
      functional recovery. Although several clinical centres worldwide have shown an
      interest in applying this approach to patients with spinal cord injury, there is
      no agreement on cell technology, and claims of beneficial results lack
      independent confirmation. Important aspects still need to be worked out at the
      laboratory level. Overall, the outlook is optimistic, but there is still some way
      to go.

PMID- 16632317
TI  - Headache and vision loss in a 41-year-old man.

PMID- 16632318
TI  - Sensitive, real-time PCR detects low-levels of contamination by Legionella
      pneumophila in commercial reagents.
AB  - In a real-time PCR assay of Legionella pneumophila (targeting the L. pneumophila
      specific mip gene and using SYBR Green dye for DNA detection in conjunction with
      the iCycler system) we detected as few as 1.3 copies of a mip gene in a 50-microl
      reaction from serially diluted L. pneumophila genomic DNA. However, cycle
      threshold (C(T)) were yielded and DNA product detected in our no-template
      negative controls and the phenomenon persisted when two separate batches of PCR
      reagents and water from two different biochemical companies were tested. Since L.
      pneumophila can be widespread in municipal water supplies, the commercial
      reagents, especially the reagent water (80% of the reaction volume), could be the
      source of contamination. To test this hypothesis, we treated Millipore Milli-Q
      water by filtering through a 0.2 microm-pore-size polycarbonate filter to remove
      bacteria prior to autoclaving. Real-time PCR using this water had no
      contamination. Our finding is indirect evidence that commercially available
      purified water can harbor low level contamination by L. pneumophila DNA that has
      escaped purification processes. This presents a challenge when developing a
      sensitive DNA-based bacterial detection method if the target organism or its DNA
      is a common contaminant of necessary reagents.

PMID- 16632319
TI  - Does self-efficacy influence leg muscle pain during cycling exercise?
AB  - This experiment examined the effect of a manipulation of self-efficacy beliefs on
      perceptions of leg muscle pain during moderate-intensity cycling exercise among
      women. Low to moderately active college-age women (n = 28) were randomly assigned
      to 1 of 2 conditions that were designed to either increase or decrease efficacy
      beliefs for engaging in moderate intensity physical activity. Efficacy was
      manipulated based on bogus feedback after a maximal incremental exercise test.
      Within 2-3 days after the efficacy manipulation, participants completed 30 min of
      cycling on an ergometer at 60% peak oxygen consumption. Perceptions of leg muscle
      pain, as well as work rate and oxygen consumption, were recorded during exercise.
      There was an initial relationship between baseline self-efficacy and pain ratings
      during a maximal incremental exercise test. Although the provision of bogus
      feedback was effective for manipulating self-efficacy, there was no differential
      effect on leg muscle pain intensity ratings during the 30 min bout of moderate
      intensity cycling. The results imply that our manipulation of self-efficacy for
      prolonged exercise does not influence leg muscle pain during moderate-intensity
      exercise among low to moderately active young females. PERSPECTIVE: We examined
      the influence of self-efficacy on muscle pain during exercise. Although we did
      not identify a significant influence of efficacy on pain, our research highlights
      novel research directions. Future research could potentially help identify self
      efficacy as a means of decreasing pain during exercise and ultimately enhancing
      physical activity participation.

PMID- 16632320
TI  - Biopsychosocial profiles of different pain diagnostic groups.
AB  - Different pain diagnoses have been examined separately in various research
      studies. The major aim of the present investigation was to add to the current
      understanding of the various groups of patients who make up the chronic pain
      population. This study expanded the research literature by including 7 different
      predominantly chronic pain syndromes (fibromyalgia, upper extremity pain,
      cervical pain, thoracic pain, lumbar pain, lower extremity pain, and headache).
      These 7 groups were examined by using a broad array of variables focusing on
      demographic, self-reported psychosocial, and physical/functional factors. There
      were 661 patients included from an interdisciplinary treatment program who had
      been given 1 physical pain diagnosis. Results revealed differences among the 7
      groups with regard to self-reported physical/functional limitations. The headache
      group had less physical/functional impairment than most of the other groups. On
      the other hand, the lumbar, fibromyalgia, and lower extremity groups had the most
      physical/functional problems. On self-reported psychosocial measures, the
      fibromyalgia group had the most difficulties, and the lower extremity and lumbar
      groups had fewer problems in this area. Overall, though, besides the fibromyalgia
      group, there was a lack of differences among the other groups on the psychosocial
      measures. PERSPECTIVE: Biopsychosocial profiles were examined for different pain
      diagnostic groups. Seven different pain groups were compared. It was discovered
      that, in general, the lumbar, fibromyalgia, and lower extremity groups reported
      more physical/functional limitations, and the fibromyalgia and headache groups
      reported more psychosocial difficulties.

PMID- 16632321
TI  - Parent and child anxiety sensitivity: relationship to children's experimental
      pain responsivity.
AB  - Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to
      childhood learning history for somatic symptoms, suggesting that parental AS may
      impact children's responses to pain. Using structural equation modeling, we
      tested a conceptual model in which parent AS predicted child AS, which in turn
      predicted a hypothesized latent construct consisting of children's pain intensity
      ratings for 3 laboratory pain tasks (cold pressor, thermal heat, and pressure).
      This conceptual model was tested in 211 nonclinical parent-child pairs (104
      girls, 107 boys; mean age 12.4 years; 178 mothers, 33 fathers). Our model was
      supported in girls only, indicating that the sex of the child moderated the
      hypothesized relationships. Thus, parent AS was related to child laboratory pain
      intensity via its contribution to child AS in girls but not in boys. In girls,
      42% of the effect of parent AS on laboratory pain intensity was explained via
      child AS. In boys, there was no clear link between parent AS and child AS,
      although child AS was predictive of experimental pain intensity across sex. Our
      results are consistent with the notion that parent AS may operate via healthy
      girls' own fear of anxiety symptoms to influence their responses to laboratory
      pain stimuli. PERSPECTIVE: The present study highlights sex differences in the
      links among parent and child anxiety sensitivity (fear of anxiety sensations) and
      children's experimental pain responses. Among girls, childhood learning history
      related to somatic symptoms may be a particularly salient factor in the
      development of anxiety sensitivity and pain responsivity.

PMID- 16632322
TI  - Translation, cross-cultural adaptation, reliability, and validity of the German
      version of the Coping Strategies Questionnaire (CSQ-D).
AB  - The aim of this study was to translate and cross-culturally adapt the American
      version of the Coping Strategies Questionnaire (CSQ) and to test the reliability
      and validity of the German version (CSQ-D). The CSQ was translated and cross
      culturally adapted following international guidelines. Reliability and validity
      were tested in 62 individuals with chronic musculoskeletal pain syndromes. For
      the concurrent criterion-related validity the CSQ-D scales were compared with the
      German Pain Coping Questionnaire (FESV-BW), and for the construct validity with
      the German Short Form 36 (SF-36). The translation process proceeded without major
      difficulties. In testing for reliability, the CSQ-D as a whole had a Cronbach's
      alpha of .94 and an intraclass correlation coefficient of .89 (95% CI .86-.98).
      The total CSQ-D score was correlated to the FESV-BW scales with scores of r =
      0.32-0.55 and with the SF-36 Mental Component Summary with scores of r = 0.32
      0.53. The CSQ-D is a precisely translated and highly reliable instrument in the
      assessment of chronic pain coping strategies. Its concurrent criterion-related
      validity and construct validity are low. The main reason for the low level of
      agreement between the CSQ-D and the FESV-BW was revealed by factor analysis.
      PERSPECTIVE: This paper presents the German version of the Coping Strategies
      Questionnaire (CSQ-D) together with the results of clinimetric testing. The CSQ-D
      is a feasible and reliable outcome measure to be used in trials with German
      speaking patients or large multicenter multinational trials to assess pain coping
      strategies in patients with chronic musculoskeletal pain.

PMID- 16632323
TI  - Covariance among age, spinal p38 MAP kinase activation and allodynia.
AB  - This study examined effects of age (young rats, approximately 35 days, vs mature
      rats, approximately 75-110 days) on spinal nerve ligation (SNL)-induced tactile
      allodynia and phosphorylation of p38 (as measured by phospho-p38 MAP kinase [P
      p38]) in dorsal root ganglia and spinal cord. Effects of SNL combined with spinal
      nerve transection also were assessed. Mature rats displayed milder SNL-induced
      allodynia than young rats. Addition of spinal nerve transection distal to the
      ligation in older animals resulted in an allodynia comparable to that seen in
      young animals. In DRG, both groups displayed early (5 h) and late (10 days) peaks
      in P-p38 following surgery as compared to naive rats. Tight nerve ligation plus
      transection had no additional effect on P-p38 levels in DRG. In spinal cord,
      young rats had increased levels of P-p38 from 5 h to 3 days after SNL.
      Phosphorylated p38 levels then decreased, with a second peak at 10 days. In
      contrast, spinal cord from mature rats showed less early p38 phosphorylation,
      although they also displayed a late 10-day peak. Addition of a transection to the
      ligation produced restoration of the early peak along with intensification of
      allodynia. Alterations of spinal P-p38 at early time points thus seem to covary
      with intensity of tactile allodynia. PERSPECTIVE: Age and modifications to spinal
      nerve ligation, a common model of neuropathic pain, influence spinal p38
      phosphorylation and allodynia. Early levels of spinal P-p38 seem to covary with
      allodynia intensity. This may mean that small variations of an injury could
      affect the therapeutic window of a p38 antagonist.

PMID- 16632324
TI  - Hypervigilance to learned pain signals: a componential analysis.
AB  - We report 2 experiments investigating hypervigilance to pain signals in healthy
      individuals. In order to allow a detailed analysis, we decomposed attention in 3
      different processes: 1) initial shifting, 2) engagement, and 3) disengagement. We
      used a spatial cueing paradigm in which the location of targets is validly or
      invalidly predicted by spatial cues. In the first experiment, cues were
      differentially conditioned to create pain signals, allowing the investigation of
      engagement and disengagement of attention. Because this procedure does not allow
      an adequate isolation of the shift component, we introduced a new adaptation of
      the spatial cueing paradigm in the second experiment, in which targets instead of
      cues were differentially conditioned. We replicated previous findings, showing
      enhanced engagement to and retarded disengagement from pain signals compared to
      control signals. In addition, we demonstrated that participants were still
      hypervigilant to pain signals after extinction. We were not able to demonstrate
      speeded shifting to pain signals. Instead we found a generally faster detection
      of pain signals compared to control signals. We conclude that hypervilance to
      pain signals does not emerge as rapid initial shifting to the pain signal but
      rather as enhanced processing once it is detected. Theoretical and clinical
      implications of these findings are discussed. PERSPECTIVE: We investigated the
      fundamental processes associated with hypervigilance to pain. Our findings
      suggest that treatment approaches using attention techniques should not focus on
      preventing patients to shift their attention to the pain but rather on
      diminishing the threat value and learning to disengage from their pain.

PMID- 16632325
TI  - Morphine antinociceptive potency on chemical, mechanical, and thermal nociceptive
      tests in the rat.
AB  - Many tests are used to assess nociception in laboratory animals. The objective of
      this study was to compare morphine potency across tests. Rats were injected with
      saline or morphine (1-20 mg/kg SC), and nociception was assessed 15-20 min later.
      A consistent definition of antinociception-a change in response greater than 4
      times the standard deviation above the mean for the saline-treated controls-was
      used to compare morphine potency on different tests. These data revealed 4
      things. 1) Morphine potency was greatest on the paw pressure, hot plate, and tail
      withdrawal tests and lowest on the formalin test. 2) Stimulus intensity had no
      effect on morphine potency on the hot plate (ED50 = 4.5, 2.8, and 2.6 mg/kg for
      49 degrees C, 52 degrees C, and 55 degrees C tests, respectively) or tail
      withdrawal tests (ED50 = 2.9 and 2.6 for 48 degrees C and 52 degrees C water,
      respectively). 3) Assessment of morphine potency using a within-subjects
      cumulative dosing procedure resulted in lower ED50 values compared to data
      collected using a between-subjects design (hot plate: 2.6 vs 4.9; tail
      withdrawal: 2.6-2.9 vs 5.7 mg/kg). 4) Adjusting the cutoff value from 4 to 5, 6,
      7, and 8 standard deviations greater than the mean resulted in a progressive
      increase in ED50 values. These data demonstrate that morphine potency is
      dependent, in part, on the nociceptive test even when all other factors (eg,
      species, strain, age, gender, and cutoff value) are held constant. PERSPECTIVE:
      The ability of morphine to block nociception is influenced by many factors. The
      present study shows that the test used to assess nociception, but not the
      stimulus intensity, can have a dramatic effect on morphine potency. This finding
      shows that morphine potency varies depending on how pain is assessed.

PMID- 16632326
TI  - Pain discomfort and crevicular fluid changes induced by orthodontic elastic
      separators in children.
AB  - The objective of the present investigation was to study the experience of pain
      after placement of orthodontic elastic separators and the possible associations
      with the gingival crevicular fluid (GCF) composition changes at the level of
      interleukin 1-beta (IL-1beta), substance P (SP), and prostaglandin-E2 (PGE2).
      Eighteen children (mean age 10.8 yrs) in the beginning of the orthodontic
      treatment were included. Molar elastic separators were inserted mesially to 2
      first upper or lower molars. One of the antagonist molars served as control. The
      GCF was collected from the distobuccal and distopalatal sites from each molar,
      before (day -7, day 0) and after the placement of separators (1 h, day 1, and day
      7). Pain intensity was recorded using a visual analog scale (VAS). The contents
      of IL-1beta, SP, and PGE2 were determined by enzyme-linked immunosorbent assay.
      Pain intensity increased after 1 h (VAS = 11) and remained high on day 1 (VAS =
      13). On day 7, no significant pain was reported. After 1 h, 1 day, and 7 days,
      mean GCF IL-1beta levels were significantly elevated at treatment teeth compared
      to control teeth (highest day 1). The GCF levels of SP and PGE2 for the treatment
      teeth were significantly higher at day 1 and day 7 than the control teeth. All 3
      mediators remained at baseline levels throughout the experiment for the control
      teeth. The intensity of pain at 1 h was associated to PGE2 levels (R2 = 0.38; P <
      .05), whereas at day 1, the intensity of pain was associated to IL-1beta levels
      (R2 = 0.63, P < .0001). Thus, we report a rapid release of biochemical markers (1
      h) that peaked after 1 day and partially decreased 7 days later. The intensity of
      pain followed a similar pattern. Associations were found between the experience
      of pain intensity and the GCF mediator levels. PERSPECTIVE: The study may help to
      detect, in an initial stage, individuals prone to perceive higher level of pain
      during orthodontic treatment. This may help in the development of methods that
      will better control and/or alleviate the discomfort of pain during tooth
      movement.

PMID- 16632327
TI  - Neurochemical diversity of neurogliaform cells in the human primary motor cortex.
AB  - Neurogliaform cells of area 4 of the human motor cortex were found to express
      choline acetyl transferase (ChAT), gamma-aminobutyric acid, and calbindin. GABA-
      and calbindin-positive NGCs were mainly localized in layers II and VI and were
      relatively rare in layer I of the cortex. ChAT-positive NGCs were observed in the
      upper and middle thirds of layer II, occurring occasionally in layer I and the
      upper portion of layer III. Their numbers were low compared to those of GABA- and
      calbindin-positive NGCs in layers II/III. The dendrites of ChAT-positive NGCs
      were short and few in number. Axonal arborizations of neighboring ChAT-positive
      cells interpenetrated considerably so that each ChAT-positive cell body was
      normally surrounded by axonal trees of the parent and a few other ChAT-positive
      NGCs. NGC axon collaterals surrounded small neuropil areas containing perikarya
      presumptive pyramidal neurons. The findings are discussed in the context of
      information processing in cortical modules and interaction of excitatory and
      inhibitory interneurons.

PMID- 16632328
TI  - The role of sodium channels in chronic inflammatory and neuropathic pain.
AB  - Clinical and experimental data indicate that changes in the expression of voltage
      gated sodium channels play a key role in the pathogenesis of neuropathic pain and
      that drugs that block these channels are potentially therapeutic. Clinical and
      experimental data also suggest that changes in voltage-gated sodium channels may
      play a role in inflammatory pain, and here too sodium-channel blockers may have
      therapeutic potential. The sodium-channel blockers of interest include local
      anesthetics, used at doses far below those that block nerve impulse propagation,
      and tricyclic antidepressants, whose analgesic effects may at least partly be due
      to blockade of sodium channels. Recent data show that local anesthetics may have
      pain-relieving actions via targets other than sodium channels, including neuronal
      G protein-coupled receptors and binding sites on immune cells. Some of these
      actions occur with nanomolar drug concentrations, and some are detected only with
      relatively long-term drug exposure. There are 9 isoforms of the voltage-gated
      sodium channel alpha-subunit, and several of the isoforms that are implicated in
      neuropathic and inflammatory pain states are expressed by somatosensory primary
      afferent neurons but not by skeletal or cardiovascular muscle. This restricted
      expression raises the possibility that isoform-specific drugs might be analgesic
      and lacking the cardiotoxicity and neurotoxicity that limit the use of current
      sodium-channel blockers. PERSPECTIVE: Changes in the expression of neuronal
      voltage-gated sodium channels may play a key role in the pathogenesis of both
      chronic neuropathic and chronic inflammatory pain conditions. Drugs that block
      these channels may have therapeutic efficacy with doses that are far below those
      that impair nerve impulse propagation or cardiovascular function.

PMID- 16632329
TI  - The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo
      controlled trial.
AB  - OBJECTIVE: Worldwide, conventional antipsychotic medication continues to be used
      extensively, and tardive dyskinesia (TD) remains a serious complication. The
      primary objective of the present study was to compare the efficacy of EPA versus
      placebo in reducing symptoms of TD. METHOD: This was a 12-week, double-blinded,
      randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication,
      in patients with schizophrenia or schizoaffective disorder, with established TD.
      RESULTS: Eighty-four subjects were randomized, of whom 77 were included in the
      analysis. Both the EPA and placebo groups displayed significant baseline to
      endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores,
      but there were no significant between-group differences (p=0.4). Response rates
      (>or=30% improvement in TD symptoms) also did not differ significantly between
      EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a
      post-hoc linear mixed model repeated measures analysis of variance indicated an
      effect for treatment group and duration of TD. The EPA-treated patients had
      significantly greater mean reductions in dyskinesia scores initially, although
      this was not sustained beyond 6 weeks. CONCLUSIONS: This trial failed to
      demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary
      efficacy measure. However, a modest and transient benefit is suggested in
      patients with more recent onset of TD. The lack of clear-cut efficacy could be
      explained on the basis of the dose of EPA being too low, the study being
      underpowered, TD being too chronic in the majority of cases, differences in
      dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

PMID- 16632330
TI  - Evidence for impaired mnemonic strategy use among patients with schizophrenia
      using the part-list cuing paradigm.
AB  - PURPOSE: Strategic and mnemonic abilities of person with schizophrenia (SCZ) were
      studied using a part-list cuing (PLC) task. In this task, presentation of
      retrieval cues in the form of a subset of studied words typically impairs recall
      of the remaining items. This impairment is thought to reflect a disruption of
      participants' natural retrieval strategies. METHODS: Participants with SCZ and
      healthy controls (ns = 28) studied word lists with three different levels of
      semantic organization: (a) unrelated, (b) categorized, but presented in a random
      order, and (c) presented by category. For each type of list, participants
      recalled words under both free-recall and PLC conditions. RESULTS: Consistent
      with SCZ-related impairment of strategic retrieval processes, the SCZ group was
      less disrupted by PLC interference than controls in the unrelated-list condition.
      Comparison of free recall across lists also indicated a consistent deficit in SCZ
      despite varying levels of difficulty and retrieval contexts. Nonetheless, the SCZ
      group demonstrated parallel improvement to the healthy group with increasing list
      organization. CONCLUSIONS: These results provide evidence of deficient retrieval
      processes in SCZ in a context placing maximal requirements for utilization of
      self-initiated, effortful, mnemonic strategies. Unlike most extant results
      demonstrating mnemonic impairment in persons with SCZ, the present results cannot
      be accounted for by task difficulty; SCZ participants' recall was less disrupted
      by PLC than was that of healthy participants. Results also demonstrated that SCZ
      participants could benefit, in terms of recall and strategy use, from list
      organization when this structure was explicitly provided at test.

PMID- 16632331
TI  - When a schizophrenic deficit becomes a reasoning advantage.
AB  - A deficit in context processing has been proposed to be one of the major
      deficiencies in schizophrenia. A demanding reasoning task, known to promote a
      very reproducible bias (i.e., a reasoning error) in healthy subjects, triggered
      by a misleading context, was administered in 26 schizophrenic patients and 26
      healthy participants. Responses at random were checked by including an additional
      group of 11 schizophrenic patients who performed a control version of the task.
      We showed that patients presented a surprising imperviousness to the reasoning
      bias and had significantly better logical performances than their paired healthy
      participants. This finding demonstrates that there are some problem solving
      situations where disregarding contextual information, a cognitive deficit that
      usually impairs schizophrenic patients gives them a cognitive advantage over
      healthy controls.

PMID- 16632332
TI  - Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia.
AB  - Neurodevelopmental changes may underlie the brain dysfunction seen in
      schizophrenia. While advances have been made in our understanding of the genetics
      of schizophrenia, little is known about how non-genetic factors interact with
      genes for schizophrenia. The present analysis of genes potentially associated
      with schizophrenia is based on the observation that hypoxia prevails in the
      embryonic and fetal brain, and that interactions between neuronal genes,
      molecular regulators of hypoxia, such as hypoxia-inducible factor 1 (HIF-1), and
      intrinsic hypoxia occur in the developing brain and may create the conditions for
      complex changes in neurodevelopment. Consequently, we searched the literature for
      currently hypothesized candidate genes for susceptibility to schizophrenia that
      may be subject to ischemia-hypoxia regulation and/or associated with vascular
      expression. Genes were considered when at least two independent reports of a
      significant association with schizophrenia had appeared in the literature. The
      analysis showed that more than 50% of these genes, particularly AKT1, BDNF,
      CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1,
      NR4A2/NURR1, PRODH, RELN, RGS4, RTN4/NOGO and TNF, are subject to regulation by
      hypoxia and/or are expressed in the vasculature. Future studies of genes proposed
      as candidates for susceptibility to schizophrenia should include their possible
      regulation by physiological or pathological hypoxia during development as well as
      their potential role in cerebral vascular function.

PMID- 16632333
TI  - Altered brain activation in dorsolateral prefrontal cortex in adolescents and
      young adults at genetic risk for schizophrenia: an fMRI study of working memory.
AB  - OBJECTIVE: Adult first-degree relatives of persons with schizophrenia carry
      elevated genetic risk for the illness, demonstrate working memory (WM)
      impairments, and manifest alterations in dorsolateral prefrontal cortical (DLPFC)
      function during WM. Because substantially less is known about these phenotypes in
      adolescent subjects we sought to demonstrate that young relatives of persons with
      schizophrenia manifest impaired WM and altered prefrontal activation. METHODS:
      Participants were 21 non-psychotic, unmedicated first-degree relatives of persons
      with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed
      type and 24 unmedicated controls, recruited from the community and hospitals in
      metropolitan Boston (ages 13-28). We compared groups on an auditory WM task with
      interference prior to scanning and used functional magnetic resonance imaging
      (fMRI) to compare groups while performing visual 2-back WM and control vigilance
      tasks. Blood oxygen level dependent signal change was measured using two whole
      brain gradient echo EPI pulse acquisitions (21 contiguous, 5mm axial slices),
      acquired on a Siemens 1.5T MR scanner. Data were analyzed using Statistical
      Parametric Mapping-99. RESULTS: The high risk subjects were significantly
      impaired on the auditory WM task, had significantly greater Phobic Anxiety, and
      marginally greater Psychoticism than controls on the Symptom Checklist-90
      Revised, and showed significantly greater task-elicited activation in the right
      DLPFC (BA 46). Psychopathology, IQ, and in-scanner WM performance did not account
      for group differences in brain activation. CONCLUSIONS: Data support a
      physiological difference (an exaggerated fMRI response) in DLPFC in adolescents
      at genetic risk for schizophrenia, independent of psychosis. Future work can
      study the relationship of these measures to possible onset of schizophrenia.

PMID- 16632334
TI  - Interaction of cellulase with sodium dodecyl sulfate at critical micelle
      concentration level.
AB  - The interactions between Trichoderma reesei cellulase and an anionic surfactant,
      sodium dodecyl sulfate (SDS), at critical micelle concentration level have been
      investigated using isothermal titration calorimetry, fluorescence spectroscopy,
      and circular dichroism. SDS micelles have dual interactions with cellulase:
      electrostatic at first and then hydrophobic interactions. When the concentration
      of SDS is smaller than 45.0mM, SDS micelles cause a partial loss in the
      hydrolytic activity together with a steep decrease in the alpha-helical content
      of cellulase. With further increasing the concentration of SDS, however, a re
      formation of the alpha-helical structure and a partial recovery of the hydrolytic
      activity of cellulase induced by SDS micelles are observed. Taken together, these
      results indicate that SDS micelles exert dual effects on cellulase through
      binding as both a denaturant and a recovery reagent.

PMID- 16632335
TI  - A system for studying the effect of mechanical stress on the elongation behavior
      of immobilized plant cells.
AB  - The ability to apply controllable mechanical compressive force is essential for
      the study of plant cells responses to environmental stimulations. The work
      presented here aims towards establishing a system, which consists of a fabricated
      apparatus (including a loading unit, displacement sensor, data collector and
      processor, and a feedback control) and a protocol for test specimen preparation
      and force loading. By using a force-feedback control circuit coupled to a
      microchip, delivering the pre-defined and actual controlled stimulus is achieved.
      To calibrate the apparatus, the corresponding voltages are compared to the known
      weights. A linear regression is fit to the experimental data and a standardized
      coefficient of 0.998 is calculated. The morphological changes in response to
      mechanical stresses were investigated in agarose gel embedded chrysanthemum
      protoplasts, which tended to be elongated with a preferential axis oriented
      perpendicularly to the compressive stress direction. The results also indicated
      that there existed a certain dose-dependent relationship between the intensity of
      compressive force and the stress-induced responses. Additionally, the elongation
      response with preferential orientation was inhibited by application of RGD
      peptides, and its inverted sequence, DGR peptides failed to antagonize the effect
      of mechanical force on elongation performance.

PMID- 16632337
TI  - Differentiation of memory B and T cells.
AB  - In the past few years progress has been made in understanding the molecular
      mechanisms that underlie the initial generation, and the ensuing differentiation
      and maintenance, of humoral and cellular immunity. Although B and T cell
      immunological memory contribute to protective immunity through fundamentally
      distinct effector functions, interesting analogies are becoming apparent between
      the two memory compartments. These include heterogeneity in function, anatomical
      location and phenotype, which probably relate to differential environmental cues
      during the early priming events as well as the later differentiation phases.
      Detailed definition of the molecular and cellular signals involved in the
      development of immunological memory, and the relative contributions of different
      memory subsets to protective immunity, remains an important goal.

PMID- 16632338
TI  - Pumping RNA: nuclear bodybuilding along the RNP pipeline.
AB  - Cajal bodies (CBs) are nuclear subdomains involved in the biogenesis of several
      classes of small ribonucleoproteins (RNPs). A number of recent advances highlight
      progress in the understanding of the organization and dynamics of CB components.
      For example, a class of small Cajal body-specific (sca) RNPs has been discovered.
      Localization of scaRNPs to CBs was shown to depend on a conserved RNA motif.
      Intriguingly, this motif is also present in mammalian telomerase RNA and the
      evidence suggests that assembly of the active form of telomerase RNP occurs in
      and around CBs during S phase. Important steps in the assembly and modification
      of spliceosomal RNPs have also been shown to take place in CBs. Additional
      experiments have revealed the existence of kinetically distinct subclasses of CB
      components. Finally, the recent identification of novel markers for CBs in both
      Drosophila and Arabidopsis not only lays to rest questions about the evolutionary
      conservation of these nuclear suborganelles, but also should enable forward
      genetic screens for the identification of new components and pathways involved in
      their assembly, maintenance and function.

PMID- 16632339
TI  - Nuclear lamins, diseases and aging.
AB  - Nuclear lamins are type V intermediate filament proteins. They are the major
      building blocks of the peripheral nuclear lamina, a complex meshwork of proteins
      underlying the inner nuclear membrane. In addition to providing nuclear shape and
      mechanical stability, they are required for chromatin organization, transcription
      regulation, DNA replication, nuclear assembly and nuclear positioning. Over the
      past few years, interest in the lamins has increased because of the
      identification of at least 12 distinct human diseases associated with mutations
      in the LMNA gene, which encodes A-type lamins. These diseases, collectively
      termed laminopathies, affect muscle, adipose, bone, nerve and skin cells and
      range from muscular dystrophies to accelerated aging.

PMID- 16632340
TI  - Electrochemical oxidation for landfill leachate treatment.
AB  - This paper aims at providing an overview of electrochemical oxidation processes
      used for treatment of landfill leachate. The typical characteristics of landfill
      leachate are briefly reviewed, and the reactor designs used for electro-oxidation
      of leachate are summarized. Electrochemical oxidation can significantly reduce
      concentrations of organic contaminants, ammonia, and color in leachate.
      Pretreatment methods, anode materials, pH, current density, chloride
      concentration, and other additional electrolytes can considerably influence
      performance. Although high energy consumption and potential chlorinated organics
      formation may limit its application, electrochemical oxidation is a promising and
      powerful technology for treatment of landfill leachate.

PMID- 16632341
TI  - Report on waste dump sites around Bangalore.
AB  - The present work aims at identifying, locating and quantifying the industrial and
      domestic waste dump sites located in and around Bangalore urban and rural
      districts of Karnataka state, India. Bangalore has a population of 6 million and
      has more than 2000 industries working at various industrial estates and other
      locations around the city. It was reported that about 1500 tons of municipal
      waste per day is being generated from Bangalore city. Studies reveal that there
      is no scientific treatment and disposal facility for scientific management of the
      waste generated. The waste from industries and community areas is disposed in an
      unscientific manner at several open dump sites across the city. There are more
      than 60 dump sites consisting of both municipal and industrial waste existing in
      and around Bangalore city; the locations are totally unhygienic. Based on the
      experience gained from field visits, physical observation of the waste disposed,
      quantity and nature of the waste disposed, each site was given with a grading
      based on polluting potential of the site. For selected sites, ground water
      samples were collected from nearby surface or bore wells and analysed for
      possible contamination. From the study, it was found that the site needed
      immediate attention and comes under severe impact category of 27 numbers and that
      of medium and low impact are 18 and 6 numbers, respectively. The disposal sites
      have got tremendous potential of spreading the epidemics/diseases to the people
      living in their immediate vicinity and at nearby places.

PMID- 16632342
TI  - Brain cancer stem-like cells.
AB  - Both stem cells and cancer cells are thought to be capable of unlimited
      proliferation. Moreover, many tumours and cancer cell lines express stem cell
      markers, including adenosine triphosphate (ATP)-binding cassette transporters, by
      which the cells pump out specific fluorescent dyes as well as anti-cancer drugs,
      suggesting either that cancer cells resemble stem cells or that cancers contain
      stem-like cells. Using the common characteristics of brain tumour cells and
      neural stem cells, several research groups have succeeded in identifying stem
      like cells (cancer stem-like cells) in brain tumours and brain cancer cell lines.
      The purified cancer stem-like cells, but not the other cancer cells, self-renew
      and form tumours when transplanted in vivo. Thus, cancer stem-like cells in brain
      tumours might be a crucial target for anti-brain tumour therapy.

PMID- 16632343
TI  - Adverse effects to quality of life arising from treatment can recover with
      intermittent androgen suppression in men with prostate cancer.
AB  - Health-related quality of life (HQOL) research is a means of broadening the
      assessment of treatment effects. This longitudinal study investigated the dynamic
      change to quality of life (QOL) and testosterone dependant physiology in men
      commencing an intermittent maximal androgen blockade program (IMAB). Two hundred
      and fifty men were accrued to the multi-centre study of IMAB (Flutamide 250 mg
      TDS, Leuprolide 22.5 mg depot) ceasing treatment after 9 months if PSA <4 ng/ml,
      and restarting when PSA >20 ng/ml. QOL was assessed every 3 months for 30 months
      using the EORTC QLQ-C30 and EORTC QLQ-PR25 module. Data completion for the whole
      study was 90%. At baseline, our cohort was less symptomatic and had better
      function than the EORTC reference cohort, which may be related to a shift in
      clinical practice with time. Testosterone suppression (AS) lead to a significant
      reduction in global HQOL and deterioration in most function and symptom scales.
      During the off period, there was a trend of progressive improvement in HQOL that
      paralleled testosterone recovery but was slower than the rate of deterioration
      during the treatment phase. Maximum recovery of HQOL occurred most frequently by
      months 9-12. Testosterone recovery was slower and less complete in older men, and
      lead to concomitant poorer HOQL recovery. Whilst the magnitude of mean change to
      scale scores was small, there was a consistent and simultaneous deterioration
      during maximal androgen blockade (MAB) and improvement during androgen recovery.
      Older men are more likely to show an impaired testosterone recovery, and this was
      paralleled by a slower HQOL recovery. Newer methods of analysis to describe
      results in a way that has meaning to the individual patient are warranted.

PMID- 16632344
TI  - Prostate cancer stem cells.
AB  - Prostate cancer is the most frequently diagnosed cancer in men. Despite recent
      advances in the detection of early prostate cancer there is little effective
      therapy for patients with locally advanced and/or metastatic disease. The
      majority of patients with advanced disease respond initially to androgen ablation
      therapy. However, most go on to develop androgen-independent tumours that
      inevitably are fatal. A similar response is seen to chemotherapeutic and
      radiotherapy treatments. As a result, metastatic prostate cancer remains an
      incurable disease by current treatment strategies. Recent reports of cancer stem
      cells have prompted questions regarding the involvement of normal stem/progenitor
      cells in prostate tumour biology, their potential contribution to the tumour
      itself and whether they are the cause of tumour initiation and progression.
      Although still controversial, the cancer stem cell is likely to be the most
      crucial target in the treatment of prostate cancer, and a thorough understanding
      of its biology, particularly of how the cancer stem cell differs from the normal
      stem cell, might allow it to be targeted selectively and eliminated, thus
      improving therapeutic outcome.

PMID- 16632345
TI  - Stem cell plasticity and tumour formation.
AB  - Stem cell plasticity refers to the ability of certain stem cells to switch
      lineage determination and generate unexpected cell types. This review applies
      largely to bone marrow cells (BMCs), which appear to contribute positively to the
      regeneration of several damaged non-haematopoietic tissues. This beneficial
      effect on regeneration may be a direct result of BMCs giving rise to organ
      parenchymal cells. Alternatively, it could be due to BMCs fusing with existing
      parenchymal cells, or providing paracrine growth factor support, or contributing
      to neovascularisation. In the context of oncology, BMC derivation of the tumour
      stroma and vasculature has profound biological and therapeutic implications, and
      there are several examples of carcinomas seemingly being derived from BMCs.

PMID- 16632346
TI  - Analysis of patients with supratentorial primitive neuro-ectodermal tumours
      entered into the SIOP/UKCCSG PNET 3 study.
AB  - The SIOP PNET 3 study was designed to determine whether 10 weeks of moderately
      intensive chemotherapy given after surgery and before radiotherapy (RT) would
      improve the outcome for patients with primitive neuroectodermal tumours (PNETs)
      compared with RT alone. Patients with a histological diagnosis of supratentorial
      PNET (StPNET) and no radiological evidence of metastatic disease were initially
      eligible for randomisation to either chemotherapy followed by craniospinal RT 35
      Gy in 21 fractions with a boost of 20 Gy in 12 fractions to the primary site, or
      RT alone. In respect of the increasing recognition that StPNET were high-risk
      tumours, randomisation for this group closed in November 1999. This analysis
      includes both randomised and non-randomised patients with StPNET entered into the
      study database. Sixty-eight patients aged 2.9-16.6 years (median 6.5 years) were
      included in the analysis (chemotherapy+RT: 44, RT alone: 24). Fifty-four patients
      (79%) had a non-pineal and 14 (21%) a pineal site. At a median follow-up of 7.4
      years, for all patients overall survival (OS) at 3 and 5 years was 54.4% and
      48.3%, respectively. Event-free survival (EFS) at 3 and 5 years was 50.0% and
      47.0%, respectively. There was no statistically significant difference in OS or
      EFS according to treatment received. OS (P=0.05) and EFS (P=0.03) were
      significantly better for patients with pineal primary sites. EFS for pineal
      tumours were 92.9% at 3 years and 71.4% at 5 years and for non-pineal primaries
      40.7% at 3 years and 40.7% at 5 years. This study confirmed the relatively good
      survival for non-metastatic pineal PNETs but poor survival of non-pineal StPNETs.
      There was no evidence that pre-radiation chemotherapy improved outlook. Future
      treatment programs should be directed at the particular natural history of these
      tumours, to further define prognostic factors and to explore further biological
      characteristics.

PMID- 16632347
TI  - No increase in thyroid cancer among children and adolescents in Finland due to
      Chernobyl accident.
AB  - The aim of the study was to assess whether radioactive fallout from the Chernobyl
      accident in 1986 influenced thyroid cancer incidence among children and
      adolescents in Finland. The population was divided into two: those with thyroid
      doses less than 0 6 mSv and above 0.6 mSv. Cumulative incidence of thyroid cancer
      was identified from the Finnish Cancer Registry from a population aged 0-20 years
      in 1986 with a total of 1,356,801 persons. No clear difference in underlying
      thyroid cancer incidences rates were found during the pre-Chernobyl period (1970
      1985) (rate ratio RR 0.95, 95% confidence interval CI 0.81-1.10). During the post
      Chernobyl period (1991-2003), thyroid cancer incidence was lower in the more
      exposed population than in the less exposed population (RR 0.76, 95% CI 0.59
      0.98). Our results did not indicate any increase in thyroid cancer incidence
      related to exposure to radiation from the Chernobyl accident.

PMID- 16632348
TI  - Cell permeation of a Trypanosoma brucei aldolase inhibitor: evaluation of
      different enzyme-labile phosphate protecting groups.
AB  - A series of four prodrugs directed against Trypanosoma brucei aldolase bearing
      various transient enzyme-labile phosphate protecting groups was developed.
      Herein, we describe the synthesis and evaluation of cell permeation of these
      prodrugs. The oxymethyl derivative was the most efficient prodrug with a good
      recovering of the free drug (IC(50)=20 microM) and without any measurable
      cytotoxicity.

PMID- 16632349
TI  - Synthesis and evaluation of N-aryl pyrrolidinones as novel anti-HIV-1 agents.
      Part 1.
AB  - The synthesis and preliminary structure-activity relationship of a series of
      pyrrolidinones are described. These pyrrolidinones have been characterized as
      novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) which are highly
      potent against wild-type and drug-resistant human immunodeficiency viruses (HIV
      1).

PMID- 16632350
TI  - Development of N-2,4-pyrimidine-N-phenyl-N'-alkyl ureas as orally active
      inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 2.
AB  - A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based
      on a N-2,4-pyrimidine-N-phenyl-N'-alkyl urea scaffold is described. Many of these
      compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF
      alpha production. Two analogs were tested in an in vivo rat iodoacetate model of
      osteoarthritis and shown to be orally efficacious. X-ray co-crystallization
      studies with mutated p38alpha showed that these trisubstituted ureas interact
      with the ATP-binding pocket in a pseudo-bicyclic conformation brought about by
      the presence of an intramolecular hydrogen bonding interaction.

PMID- 16632351
TI  - An improved synthesis of psammaplin A.
AB  - The marine natural product, psammaplin A, was first isolated from the
      Psammaplinaplysilla sponge in 1987. Since that time, psammaplin A has shown a
      wide spectrum of biological activities that include enzyme inhibitory activities
      resulting in antibacterial and antitumor effects. An improved synthesis of
      psammaplin A has been developed, making the compound more easily accessible for
      further biological evaluations. In this context, we find that psammaplin A is an
      effective DNA methyltransferase inhibitor in vitro but fails to alter genomic DNA
      methylation levels in treated human cancer cells.

PMID- 16632352
TI  - A ratiometric fluorescent sensor for Zn2+ based on internal charge transfer
      (ICT).
AB  - A ratiometric fluorescent chemosensor 5 was designed and synthesized based on
      internal charge transfer (ICT). The indicator absorbs and emits light in the
      visible wavelength range. In acetonitrile, blue shifts in fluorescent emission
      upon zinc binding are due to the formation of a 1:2 metal/ligand complex, which
      induced a fluorescent emission at 616 nm at the expense of the fluorescent
      emission at 672 nm.

PMID- 16632353
TI  - Development of sulfonamide compounds as potent methionine aminopeptidase type II
      inhibitors with antiproliferative properties.
AB  - We have screened molecules for inhibition of MetAP2 as a novel approach toward
      antiangiogenesis and anticancer therapy using affinity selection/mass
      spectrometry (ASMS) employing MetAP2 loaded with Mn(2+) as the active site metal.
      After a series of anthranilic acid sulfonamides with micromolar affinities was
      identified, chemistry efforts were initiated. The micromolar hits were quickly
      improved to potent nanomolar inhibitors by chemical modifications guided by
      insights from X-ray crystallography.

PMID- 16632354
TI  - A new class of selective, non-basic 5-HT2A receptor antagonists.
AB  - Based on an existing series of 5-HT2A receptor ligands containing a basic
      nitrogen, we designed a non-basic lead that had reduced affinity for both the 5
      HT2A receptor and the IKr potassium channel. The present paper describes the
      development of this lead to a novel series of non-basic piperidine sulfonamides
      and amides that have high affinity for the 5-HT2A receptor, whilst maintaining
      excellent selectivity over off target activities such as the IKr channel. This
      work has shown that the proposed pharmacophore model for the 5-HT2A receptor
      which suggests that a basic nitrogen is required for the binding of ligands is
      questionable.

PMID- 16632355
TI  - 3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands
      for the ORL-1 receptor.
AB  - A novel series of indoles and 1H-pyrrolo[2,3-b]pyridines having a piperidine ring
      at the 3-position were synthesized and found to bind with high affinity to the
      ORL-1 receptor. Structure-activity relationships at the piperidine nitrogen were
      investigated in each series. Substitution on the phenyl ring and nitrogen atom of
      the indole and 1H-pyrrolo[2,3-b]pyridine cores generated several selective high
      affinity ligands that were agonists of the ORL-1 receptor.

PMID- 16632356
TI  - Development of N-2,4-pyrimidine-N-phenyl-N'-phenyl ureas as inhibitors of tumor
      necrosis factor alpha (TNF-alpha) synthesis. Part 1.
AB  - A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based
      on an N-2,4-pyrimidine-N-phenyl-N'-phenyl urea scaffold is described. Many of
      these compounds showed low-nanomolar activity against lipopolysaccharide
      stimulated TNF-alpha production. X-ray co-crystallization studies with mutated
      p38alpha showed that these trisubstituted ureas interact with the ATP-binding
      pocket in a pseudo-bicyclic conformation brought about by the presence of an
      intramolecular hydrogen bonding interaction.

PMID- 16632357
TI  - The discovery of tetrahydrofluorenones as a new class of estrogen receptor beta
      subtype selective ligands.
AB  - Synthesis and derivatization of a series of substituted tetrahydrofluorenone
      analogs giving potent, ERbeta subtype selective ligands are described. Several
      analogs possessing ERbeta binding affinities comparable to 17beta-estradiol but
      with greater than 75-fold selectivity over ERalpha are reported.

PMID- 16632358
TI  - Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix
      metalloproteinase inhibitors.
AB  - A series of novel carboxylic acid-based alpha-sulfone MMP inhibitors have been
      synthesized and the in vitro enzyme SAR is discussed. A potential binding mode in
      the active site of the MMP-9 homology model was highlighted. These compounds are
      potent MMP-9 inhibitors and are selective over MMP-1.

PMID- 16632359
TI  - Discovery of novel isothiazole inhibitors of the TrkA kinase: structure-activity
      relationship, computer modeling, optimization, and identification of highly
      potent antagonists.
AB  - The design, synthesis, and biological evaluation of potent inhibitors of the TrkA
      kinase is presented. A homology model is created to aid in the enhancement of
      potency and selectivity of isothiazole inhibitors found during a high-throughput
      screen. Three different syntheses are utilized to make diverse analogs within
      this series. Aminoheterocycles are found to be good urea surrogates, whereas
      bicyclic substituents on the C3 thio group were found to be extremely potent TrkA
      inhibitors in kinase and cell assays.

PMID- 16632360
TI  - Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi
      renieramycin G.
AB  - Analogues of the tetrahydroisoquinoline family of antitumor antibiotics, 3-epi
      jorumycin (3) and 3-epi-renieramycin G (4), in addition to their respective
      parent natural products (-)-jorumycin (1) and (-)-renieramycin G (2) were
      evaluated against both human colon (HCT-116) and human lung (A549) cancer cell
      lines. (-)-Jorumycin (1) displayed potent growth inhibition with GI50 values in
      the low nanomolar range (1.9-24.3 nM), while compounds 2-4 were found to be
      substantially less cytotoxic (GI50 0.6-14.0 microM).

PMID- 16632361
TI  - The gross motor function measure is a valid and sensitive outcome measure for
      spinal muscular atrophy.
AB  - Spinal muscular atrophy is a genetic disease of the anterior horn cell with high
      morbidity rate in childhood. Certain drugs may be of benefit and are in or under
      consideration for Phase II trials. Outcome measures that are age appropriate and
      representative of disease activity remain under study. Several have not yet been
      validated for spinal muscular atrophy. The Gross Motor Function Measure is a
      measure of motor function. We showed previously that the Gross Motor Function
      Measure is a reliable outcome measure to assess motor function in children with
      spinal muscular atrophy. By collating our data from 40 spinal muscular atrophy
      patients, ages 5 through 17 years, we now show the validity of the Gross Motor
      Function Measure when compared to Quantitative Muscle Testing and ambulatory
      status in children with spinal muscular atrophy. The median for Gross Motor
      Function Measure total scores for walkers was 237 (range: 197-261) and for non
      walkers, 64 (range: 4-177; P<0.0001) with no distributional overlap. We conclude
      that the Gross Motor Function Measure is valid and sensitive as an outcome
      measure for clinical trials in pediatric spinal muscular atrophy.

PMID- 16632362
TI  - Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)
      -5-year follow-up.
AB  - Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)
      is a new operation procedure using a cell seeded collagen matrix for the
      treatment of localized full-thickness cartilage defects. A prospective clinical
      investigation was carried out in order to clarify whether this proves suitable
      and confirms objective and subjective clinical improvement over a period of up to
      5 years after operation. Thirty-eight patients with localised cartilage defects
      were treated with MACT. Within the context of clinical follow-up, these patients
      were evaluated for up to 5 years after the intervention. Four different scores
      (Meyers score, Tegner-Lysholm activity score, Lysholm-Gillquist score, ICRS
      score) as well as the results of six arthroscopies and biopsies obtained from
      four patients formed the basis of this study. For 15 patients, 5 or more years
      had elapsed since the operation at the time this study was completed. It was
      possible to obtain results 5 years postoperatively from 11 (73.3%) of these 15
      patients. Overall, we included 25 patients into the evaluation with a 2-year or
      longer postoperative period. Five years after transplantation 8 out of 11
      patients rated the function of their knee as much better or better than before.
      Three of the four scores showed significant improvement compared to the
      preoperative value. One score, the Tegner-Lysholm score showed improvement,
      which, however, did not prove to be significant. The significantly improved
      results on three scores after 5 years suggest that MACT represents a suitable but
      cost-intensive alternative in the treatment of local cartilage defects in the
      knee.

PMID- 16632363
TI  - Femoral component rotation in mobile-bearing total knee arthroplasty.
AB  - The surgical technique utilized for the LCS mobile-bearing since 1977 has been a
      tibial cut first method which requires determination of femoral rotation with
      tension spacing. We evaluated 38 randomly selected mobile-bearing TKA in which
      this technique was utilized. All cases had satisfactory clinical results. Spiral
      computed tomography scans measured the posterior condylar angle which is the
      angle of the femoral component posterior condyles in relation to the surgical
      transepicondylar axis. The mean femoral component alignment was 0.3 degrees of
      internal rotation to the transepicondylar axis (S.D.=2.2 degrees ; range=6
      degrees internal to 4 degrees external). Four cases (10%) were outside of 3
      degrees from the TEA. Lateral patellar tilt and subluxation was identified in one
      female who had a femoral component position of 5 degrees internal rotation. In
      90% of cases, the posterior condylar angle was within 3 degrees of the surgical
      transepicondylar axis which is regarded as the functional ideal for conventional
      methods.

PMID- 16632364
TI  - Two clinical tests for assessing lateral compartment arthritis.
AB  - Two clinical tests, the valgus tap test and the valgus skid test, are described
      which detect bone contact in the lateral compartment of the knee. They are useful
      in planning surgical intervention.

PMID- 16632365
TI  - Modified Judet's quadricepsplasty for loss of knee flexion.
AB  - We reviewed the results of a modified Judet's quadricepsplasty in eleven patients
      with inability to fully flex the knee. The patients were examined at an average
      follow-up of 49 months (4 to 108 months). Their mean pre-operative knee flexion
      was 30 degrees (range 10 degrees -50 degrees ). At the final follow-up the mean
      active flexion was improved to 100 degrees (range 70 degrees -130 degrees ) with
      an average flexion gain of 70 degrees (range 45 degrees -100 degrees ). None of
      the patients developed an extension lag. According to Judet's criteria, the
      results were three excellent, seven good and one fair. Staged quadricepsplasty is
      a useful procedure to correct the disabling flexion loss in the knee.

PMID- 16632366
TI  - A systematic review of lateral wedge orthotics--how useful are they in the
      management of medial compartment osteoarthritis?
AB  - Studies on the use of lateral wedge orthotics in the conservative management of
      medial compartment osteoarthritis are widely quoted. This approach, however, does
      not consider the disruption of the interaction between lower limb and foot and
      ankle function that lateral wedges would produce. This comprehensive, systematic
      review was therefore undertaken to evaluate all available literature to determine
      whether evidence exists to support their use. MEDLINE, EMBASE, CINAHL, Allied and
      Complimentary Medicine, PubMed, EBSCO HOST and PEDro, Abstracts of Reviews of
      Effects in the National Electronic Library for Health for Cochrane Reviews and
      manual searching were used to identify studies. was searched for trials in
      progress. Data extraction was performed by the three authors using a paper data
      extraction form which was based on the CONSORT statement and Critical Skills
      Appraisal Programme (CASP) guidelines. Overall, the results of this review
      suggest that, based on current evidence there are no major or long-term
      beneficial effects with the use of lateral wedges.

PMID- 16632367
TI  - Anticancer thiopyrano[2,3-d][1,3]thiazol-2-ones with norbornane moiety.
      Synthesis, cytotoxicity, physico-chemical properties, and computational studies.
AB  - A series of novel 9-substituted-3,7-dithia-5
      azatetracyclo[9.2.1.0(2,10).0(4,8)]tetradecen-4(8)-ones-6 have been synthesized
      by a stereoselective hetero-Diels-Alder reaction of 5-ylidene-4-thioxo-2
      thiazolidone derivatives with norbornene-2. All the compounds have been evaluated
      for antitumor activity in in vitro human tumor cell lines, and 10 of them
      possessed significant and selective cytotoxicity (MGM logGI50 approximately -4.17
      to -4.98, for individual cell lines logGI50 up to -8). COMPARE analyses of
      differential growth inhibition patterns of compounds at the GI50 level showed
      high correlations with some of the antitubulin agents. The lipophilicity of the
      compounds was studied by RP-TLC and found to correlate well with calculated logP
      values. Docking and structure-activity relationship studies produced seven QSAR
      models with 2 or 3 variables, with correlation coefficients r2>0.9 and leave-one
      out cross-validation correlation coefficients, q2>0.8.

PMID- 16632368
TI  - Nanoscale characterization of the interface between bone and hydroxyapatite
      implants and the effect of silicon on bone apposition.
AB  - Silicon plays an important role in bone mineralization and formation and is
      therefore incorporated into a wide variety of medical implants and bone grafts
      used today. The significance of silicon (Si) can be understood through an
      analysis of the mechanisms of bone bonding to calcium containing biomaterials and
      through comparisons of hydroxyapatite (HA) and silicon-substituted hydroxyapatite
      (Si-HA). The addition of Si to HA causes a decrease in grain size that
      subsequently affects surface topography, dissolution-reprecipitation rates and
      the bone apposition process. Through the use of high-resolution transmission
      electron microscopy (HR-TEM) studies, the interactions between bone and silicon
      hydroxyapatite (Si-HA) at interfaces are reviewed and related to their impact on
      bone apposition and ultimately the performance of medical implants.

PMID- 16632369
TI  - Immobilization and AFM of single 4 x 6-mer tarantula hemocyanin molecules.
AB  - The high molecular mass respiratory protein of the tarantula Eurypelma
      californicum, a 4 x 6-mer hemocyanin, was investigated by atomic force microscopy
      (AFM). Various substrates and methods were evaluated for immobilization of
      individual hemocyanin molecules on a solid surface. Samples were imaged after
      physisorption on mica and self-assembled monolayers, and after chemisorption on
      Au(111) and N-hydroxy-succinimide (NHS) functionalized surfaces. AFM measurements
      were carried out preferable in solution and contact mode, but also in Tapping
      mode and on air-dried samples. Adsorption of the protein on mica followed by
      drying and carrying out the measurements in Tapping mode gave the best results.
      In the AFM images the four hexamers of the native 4 x 6-mer hemocyanin have been
      defined. The results were compared with independent available structural data and
      represent a validation case for this technique applied for the first time on such
      giant and complex molecules. As observable in images taken by transmission
      electron microscopy and also proposed from SAXS data, 4 x 6-mers could be found
      where the half-molecules are tilted against each other. This study is a step in
      resolving conformational heterogeneities, involved in oxygen binding of
      hemocyanins, at the single-molecule level by AFM.

PMID- 16632370
TI  - Fat body of Prorhinotermes simplex (Isoptera: Rhinotermitidae): ultrastructure,
      inter-caste differences and lipid composition.
AB  - Ultrastructure of the fat body was studied in following castes and developmental
      stages of Prorhinotermes simplex: larvae of the first and the second instar,
      pseudergates, presoldiers, soldiers, nymphs, imagoes and mature ergatoid neotenic
      reproductives of both sexes. Fat body always consists of two principal cell
      types: adipocytes and urocytes. Adipocytes are characterized by a presence of
      large amounts of storage substances, namely lipid droplets, glycogen rosettes and
      proteins in the form of either biocrystals or vacuoles. Proportion of these
      components strongly varies during ontogeny. Adipocytes are equipped by a large
      central vacuole in which lipid droplets may resolve. Cytoplasm of urocytes
      contain glycogen rosettes and spherical or irregular concretions, other
      organelles are rare. Only adipocytes change their inner structure in the course
      of ontogeny: amount of glycogen decreases during the postembryonic development,
      it is the major kind of inclusion in the larvae but lacks in nymphs and imagoes;
      opposite trend is performed by lipids. The changes in protein content are less
      obvious but are explained and discussed. The total amount of triacylglycerols
      (TAGs) was found to be roughly 100microg in a pseudergate, 250microg in a nymph,
      and 30microg in a soldier. The most abundant fatty acids in TAGs are oleic (O),
      stearic (S), palmitic (P) and linoleic (L) acid. TAGs form a complex mixture with
      OOO, OPO, OLO and OOS being the most abundant isomers. Only negligible
      differences exist among the castes.

PMID- 16632371
TI  - The geometric pattern of a pillared substrate influences the cell-process
      distribution and shapes of fibroblasts.
AB  - Fibroblasts alter their shape, direction of movement, cytoskeleton arrangement,
      and focal contact when placed upon square array pillars. We prepared pillars of 1
      microm diameter, separated by 3 microm, and having 1, 5, and 10 microm heights
      using substrates displaying identical surface chemistry. When cells seeded
      initially onto the tops of the pillars, fibroblasts subsequently were immobilized
      in situ by several pillars that visibly protruded through, but did not pierce,
      the cell bodies. The cytoplasma then migrated outward with long straight lamella
      along the interval of the pillars and formed several discrete attachment zones at
      their side walls - the value of their form index (FI) was as high as 35 - which
      altered the cellular shape entirely. Most of the cells interacted with the pillar
      substrate by spreading preferentially in a particular direction, but some of them
      had the ability to undergo coincident two-direction (x and y) migration; right
      angle turn orientations led to the growth of dramatic cellular morphologies.
      Interestingly, this fibroblast's behavior variation was gradually in proportion
      to the pillar height of substrate. Our results confirm that cellular migration
      and cellular shape are both strongly affected by the geometry of the growth
      microenvironment.

PMID- 16632372
TI  - Morphological features and occurrence of degenerative characteristics in the
      hypopharyngeal glands of the paper wasp Polistes versicolor (Olivier)
      (Hymenoptera: Vespidae).
AB  - Different histochemical techniques were applied to examine the morphological
      features of the secretory cells of hypopharyngeal glands in the wasp Polistes
      versicolor. The results showed that most analyzed individuals present active
      glands with secretion stored in the cytoplasm. In some glands, morphological
      analyses revealed the presence of degenerative characteristics. Analyses of
      cellular integrity, however, did not detect dead cells. The results showed that,
      in P. versicolor, the development and regression of the hypopharyngeal glands
      were not age related, unlike glands of social bees.

PMID- 16632373
TI  - Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine
      derivative.
AB  - Studies on the development of imaging agents for targeting neuroreceptors is an
      area of considerable interest owing to the limited availability of specific as
      well as selective radiolabeled agents. Therefore, with an aim of developing a
      receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy
      tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the
      synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies
      in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain
      barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The
      other relevant observations from biodistribution studies included no significant
      uptake in any other organ and fast clearance from blood, lungs and liver.

PMID- 16632374
TI  - Immediate oxidative burst onto the leaves after cutting the stem or flooding the
      roots of Nicotiana benthamiana.
AB  - Plants may use a common defense system to respond to various abiotic and biotic
      stresses. Some hypotheses have suggested that there is a systemic signal that
      originates from the site of stress and that translocates to distant parts of the
      plant. We have detected an immediate oxidative burst onto the leaves after
      cutting the stem that lasted for 3 minutes and an immediate oxidative burst onto
      the leaves after flooding the roots of Nicotiana benthamiana that lasted for 20
      minutes. Both of the two oxidative bursts were generated within 30 seconds. This
      strongly indicated that the systemic signal was not a transportable molecule from
      the site of stress and that it could be some form of electrical signalling.

PMID- 16632375
TI  - A critical reflection on the definition of metabolic syndrome.
AB  - The metabolic syndrome (visceral obesity, dyslipidaemia, hyperglycaemia, and
      hypertension), has become one of the major public-health challenges worldwide.
      There has been growing interest in this constellation of closely related
      cardiovascular risk factors. Recently, definition and relevance of this syndrome
      have been questioned. In the present review we analyze in detail the
      epistemological issues regarding definition and the methodological approaches to
      definition of the metabolic syndrome.

PMID- 16632376
TI  - Cellular inflammatory responses: novel insights for obesity and insulin
      resistance.
AB  - Type 2 diabetes is rapidly becoming a worldwide epidemic. Obesity and sedentary
      lifestyle are the main environmental causes for the development of insulin
      resistance and type 2 diabetes. In the past decade, it has been increasingly
      recognized that obesity and insulin resistance are associated with chronic, low
      grade systemic inflammation. This review will cover the recent advances in this
      field and provide a working model explaining how cellular inflammatory responses
      arise to cope with obesity-induced metabolic stresses and how these inflammatory
      responses underlie insulin resistance.

PMID- 16632377
TI  - Does contamination buildup limit throughput for automated cryoEM?
AB  - The development of automated systems for data acquisition in cryo electron
      microscopy has enabled the possibility of acquiring very large number of images
      from a single specimen grid. We have demonstrated that over images of 250,000
      single particles can be acquired in a 24 h period. This has raised questions as
      to whether contamination buildup on the specimen limits the quality of the data
      that can be acquired during these long duration experiments and also whether the
      data acquisition session could be extended to allow acquisition of more than
      1,000,000 particles. We report here a systematic characterization of
      contamination of specimens maintained for long periods of time at liquid nitrogen
      temperatures using standard side entry cryo stages. As part of this
      characterization we developed a more reliable method for accurately estimating
      specimen ice thickness. Using the method, we were able to calibrate image
      contrast against ice thickness under a variety of magnifications, objective
      aperture positions, and defoci, and demonstrated the strong dependence of the
      calibration curve on these parameters. The results show the anti-contamination
      aperture is, as expected, critical to the prevention of contamination and that
      loading film into the microscope dramatically increases the contamination rate,
      particularly in the first 3 h after the insertion of the film box. In the absence
      of film, we were able to reproducibly demonstrate that the contamination rate can
      be limited to a rate of approximately 1 angstrom/h providing reassurance that
      contamination will not be a major limiting factor for long term cryoEM
      experiments if a CCD camera is used for the imaging.

PMID- 16632378
TI  - Mechanisms of evoked and induced responses in MEG/EEG.
AB  - Cortical responses, recorded by electroencephalography and
      magnetoencephalography, can be characterized in the time domain, to study event
      related potentials/fields, or in the time-frequency domain, to study oscillatory
      activity. In the literature, there is a common conception that evoked, induced,
      and on-going oscillations reflect different neuronal processes and mechanisms. In
      this work, we consider the relationship between the mechanisms generating
      neuronal transients and how they are expressed in terms of evoked and induced
      power. This relationship is addressed using a neuronally realistic model of
      interacting neuronal subpopulations. Neuronal transients were generated by
      changing neuronal input (a dynamic mechanism) or by perturbing the systems
      coupling parameters (a structural mechanism) to produce induced responses. By
      applying conventional time-frequency analyses, we show that, in contradistinction
      to common conceptions, induced and evoked oscillations are perhaps more related
      than previously reported. Specifically, structural mechanisms normally associated
      with induced responses can be expressed in evoked power. Conversely, dynamic
      mechanisms posited for evoked responses can induce responses, if there is
      variation in neuronal input. We conclude, it may be better to consider evoked
      responses as the results of mixed dynamic and structural effects. We introduce
      adjusted power to complement induced power. Adjusted power is unaffected by trial
      to-trial variations in input and can be attributed to structural perturbations
      without ambiguity.

PMID- 16632379
TI  - Separating respiratory-variation-related fluctuations from neuronal-activity
      related fluctuations in fMRI.
AB  - Subtle changes in a subject's breathing rate or depth, which occur naturally
      during rest at low frequencies (<0.1 Hz), have been shown to be significantly
      correlated with fMRI signal changes throughout gray matter and near large
      vessels. The goal of this study was to investigate the impact of these low
      frequency respiration variations on both task activation fMRI studies and resting
      state functional connectivity analysis. Unlike MR signal changes correlated with
      the breathing motion ( approximately 0.3 Hz), BOLD signal changes correlated with
      across-breath variations in respiratory volume ( approximately 0.03 Hz) appear
      localized to blood vessels and regions with high blood volume, such as gray
      matter, similar to changes seen in response to a breath-hold challenge. In
      addition, the respiration-variation-induced signal changes were found to coincide
      with many of the areas identified as part of the 'default mode' network, a set of
      brain regions hypothesized to be more active at rest. Regions could therefore be
      classified as being part of a resting network based on their similar respiration
      induced changes rather than their synchronized neuronal activity. Monitoring and
      removing these respiration variations led to a significant improvement in the
      identification of task-related activation and deactivation and only slight
      differences in regions correlated with the posterior cingulate at rest.
      Regressing out global signal changes or cueing the subject to breathe at a
      constant rate and depth resulted in an improved spatial overlap between
      deactivations and resting-state correlations among areas that showed
      deactivation.

PMID- 16632380
TI  - Hemispheric asymmetries in language-related pathways: a combined functional MRI
      and tractography study.
AB  - Functional lateralization is a feature of human brain function, most apparent in
      the typical left-hemisphere specialization for language. A number of anatomical
      and imaging studies have examined whether structural asymmetries underlie this
      functional lateralization. We combined functional MRI (fMRI) and diffusion
      weighted imaging (DWI) with tractography to study 10 healthy right-handed
      subjects. Three language fMRI paradigms were used to define language-related
      regions in inferior frontal and superior temporal regions. A probabilistic
      tractography technique was then employed to delineate the connections of these
      functionally defined regions. We demonstrated consistent connections between
      Broca's and Wernicke's areas along the superior longitudinal fasciculus
      bilaterally but more extensive fronto-temporal connectivity on the left than the
      right. Both tract volumes and mean fractional anisotropy (FA) were significantly
      greater on the left than the right. We also demonstrated a correlation between
      measures of structure and function, with subjects with more lateralized fMRI
      activation having a more highly lateralized mean FA of their connections. These
      structural asymmetries are in keeping with the lateralization of language
      function and indicate the major structural connections underlying this function.

PMID- 16632381
TI  - Comparing neural correlates of configural processing in faces and objects: an ERP
      study of the Thatcher illusion.
AB  - In the Thatcher illusion, a face with inverted eyes and mouth looks abnormal when
      upright but not when inverted. Behavioral studies have shown that thatcherization
      of an upright face disrupts perceptual processing of the local configuration. We
      recorded high-density EEG from normal observers to study ERP correlates of the
      illusion during the perception of faces and nonface objects, to determine whether
      inversion and thatcherization affect similar neural mechanisms. Observers viewed
      faces and houses in four conditions (upright vs. inverted, and normal vs.
      thatcherized) while detecting an oddball category (chairs). Thatcherization
      delayed the N170 component over occipito-temporal cortex to faces, but not to
      houses. This modulation matched the illusion as it was larger for upright than
      inverted faces. The P1 over medial occipital regions was delayed by face
      inversion but unaffected by thatcherization. Finally, face thatcherization
      delayed P2 over occipito-temporal but not over parietal regions, while inversion
      affected P2 across categories. All effects involving thatcherization were face
      specific. These results indicate that effects of face inversion and feature
      inversion (in thatcherized faces) can be distinguished on a functional as well as
      neural level, and that they affect configural processing of faces in different
      time windows.

PMID- 16632382
TI  - Reproducibility of odor maps by fMRI in rodents.
AB  - The interactions of volatile odorants with the approximately 1000 types of
      olfactory receptor neurons in the olfactory mucosa are represented in the
      olfactory bulb by glomerular spatial activity maps. If these spatial maps
      underlie the perceptual identification of odorants then, for a given organism,
      they must be both specific and reproducible. However, this intra-organism
      reproducibility need not be present between organisms because genetic and
      developmental studies of olfactory bulb wiring suggest that there is substantial
      variation between the glomerular arrangements of closely related organisms and
      even between the two bulbs in a given animal. The ability of functional MRI
      (fMRI) to record responses of the entire rodent olfactory bulb repeatedly within
      the same subject has made it possible to assess the reproducibility of odor
      induced spatial activity maps both within and between subjects exposed to
      equivalent stimuli. For a range of odorants, representing multiple chemical
      classes, a level of fMRI reproducibility (at 7.0 T and 9.4 T) comparable or
      superior to other cortical regions was demonstrated. While the responses of
      different bulbs to the same odorant could be localized within the same broad
      regions of the glomerular sheet, the precise magnitude and topology of the
      response within those regions were both often highly variable. These results
      demonstrate the robustness of high-field fMRI as a tool for assaying olfactory
      bulb function and provide evidence that equivalent perceptual outcomes may arise
      from divergent neural substrates.

PMID- 16632383
TI  - Distinct neural mechanisms of risk and ambiguity: a meta-analysis of decision
      making.
AB  - Converging evidence from human and animal studies suggests that decision-making
      relies upon a distributed neural network based in the frontal lobes. In
      particular, models of decision-making emphasize the involvement of orbitofrontal
      cortices (OFC) and the medial wall. While decision-making has been studied
      broadly as a class of executive function, recent models have suggested the
      differentiation between risky and ambiguous decision-making. Given recent
      emphasis on the role of OFC in affectively laden "hot" executive function and
      dorsolateral prefrontal cortex (DLPFC) in more purely cognitive "cool" executive
      function, we hypothesize that the neural substrates of decision-making may differ
      depending on the nature of the decision required. To test this hypothesis, we
      used recently developed meta-analytic techniques to examine the existent
      functional neuroimaging literature. An initial meta-analysis of decision-making,
      both risky and ambiguous, found significantly elevated probabilities of
      activation in frontal and parietal regions, thalamus, and caudate. Ambiguous
      decision-making was associated with activity in DLPFC, regions of dorsal and
      subcallosal anterior cingulate cortex (ACC), and parietal cortex. Risky decision
      making was associated with activity in OFC, rostral portions of the ACC, and
      parietal cortex. Direct statistical comparisons revealed significant differences
      between risky and ambiguous decision-making in frontal regions, including OFC,
      DLPFC, and ACC, that were consistent with study hypotheses. These findings
      provide evidence for the dissociation of neural circuits underlying risky and
      ambiguous decision-making, reflecting differential involvement of affective "hot"
      and cognitive "cool" processes.

PMID- 16632384
TI  - Can optical recordings of membrane potential be used to screen for drug-induced
      action potential prolongation in single cardiac myocytes?
AB  - INTRODUCTION: Potential-sensitive dyes have primarily been used to optically
      record action potentials (APs) in whole heart tissue. Using these dyes to record
      drug-induced changes in AP morphology of isolated cardiac myocytes could provide
      an opportunity to develop medium throughout assays for the pharmaceutical
      industry. Ideally, this requires that the dye has a consistent and rapid response
      to membrane potential, is insensitive to movement, and does not itself affect AP
      morphology. MATERIALS AND METHODS: We recorded the AP from isolated adult guinea
      pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual
      emission ratiometric system, either separately in electrically field stimulated
      myocytes, or simultaneously with an electrical AP recorded with a patch electrode
      in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was
      calibrated against membrane potential using a switch-clamp to voltage clamp the
      myocyte. RESULTS: Our data show that the ratio of the optical signals emitted at
      560/620 nm is linearly related to voltage over the voltage range of an AP,
      producing a change in ratio of 7.5% per 100 mV, is unaffected by cell movement
      and is identical to the AP recorded simultaneously with a patch electrode.
      However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was
      significantly longer than in unloaded myocytes recorded with a patch electrode
      (355.6+/-13.5 vs. 296.2+/-16.2 ms; p<0.01). Despite this effect, the apparent
      IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly
      different whether determined optically or with a patch electrode (91+/-46 vs.
      81+/-20 nM). DISCUSSION: These data show that the optical AP recorded
      ratiometrically using di-8-ANEPPS from a single ventricular myocyte accurately
      follows the action potential morphology. This technique can be used to estimate
      the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs
      APD90. Optical dyes require less technical skills and are less invasive than
      conventional electrophysiological techniques and, when coupled to ventricular
      myocytes, decreases animal usage and facilitates higher throughput assays.

PMID- 16632385
TI  - Accidents at work among people with epilepsy. Results of a European prospective
      cohort study.
AB  - Studies on accidents at work in people with epilepsy are scarce and the evidence
      that epilepsy carries an increased risk of accidents at work is mostly anecdotal.
      The present survey is a multicentre prospective cohort study of everyday life
      risks recently conducted in eight European countries (Estonia, Germany, Italy,
      the Netherlands, Portugal, Russia, Slovenia and United Kingdom) comparing
      referral children and adults with epilepsy to age- and sex-matched non-epileptic
      controls. In this context, every accident occurring during work over a 1-3 year
      follow-up was prospectively reported by patients and controls. Six hundred and
      thirty-one adult patients with epilepsy and 592 controls from this cohort have
      been studied here. Each patient and his/her control received a diary to record
      any accident or illness, with severity, circumstances, causes, consequences
      (including days off-work) and (for the cases) the possible relation to a seizure.
      A slightly higher number of unskilled workers were present among patients with
      epilepsy than in controls. Twenty-two patients with epilepsy and nine controls
      reported accidents during work (p<0.05). Only two cases reported seizure-related
      accidents. In both groups the injuries were mild (only one requiring
      hospitalization) and caused abstention from work to the same extent. In patients
      with epilepsy, the risk of accidents was unaffected by seizure type and
      frequency. This study confirms that patients with epilepsy are at higher risk of
      accidents compared to the general population. However, injuries provoked by work
      accidents are generally mild and unrelated to seizures.

PMID- 16632386
TI  - Low-dose mecamylamine improves learning of rats in the radial-arm maze repeated
      acquisition procedure.
AB  - The nicotinic antagonist mecamylamine has been widely shown to cause cognitive
      impairment. However, these effects are mainly seen with high doses. There have
      been scattered findings that low doses of mecamylamine can have the opposite
      effect. This may be due to opposite effects of low doses of mecamylamine. In the
      current study, an extensive dose-effect function of mecamylamine was
      characterized in the low-dose range. Adult female Sprague-Dawley rats were
      trained on a repeated acquisition procedure on an automated 8-arm radial maze.
      Three of the eight arms were designated as correct for any particular session.
      Five trials per session were run. The number of errors per trial to find the
      three correct arms was determined. The rats were trained on the repeated
      acquisition procedure for at least 18 sessions at which time they showed reliable
      learning each session. Then, the effect of low doses of mecamylamine between 0
      and 1 mg/kg were assessed in a repeated measures counterbalanced design. This
      dose range of mecamylamine did not affect performance on the first trial when the
      rats were naive to the array to be learned. On trials 2-5 a significant (p<.025)
      quadratic dose-effect function was seen over this dose range. The most
      substantial effect was seen with 0.125 mg/kg of mecamylamine, which caused a
      significant (p<.05) improvement relative to the saline control condition. The
      effect diminished with increasing mecamylamine doses and with the 1 mg/kg dose
      choice accuracy was back to control levels. This study showed that low doses of
      mecamylamine can effectively improve learning. A U-shaped dose-effect curve was
      documented. This suggests possible low-dose nicotinic antagonist lines of
      treatment for cognitive impairment.

PMID- 16632387
TI  - Effect of 12-hour road transportation on physiological, immunological and
      haematological parameters in bulls housed at different space allowances.
AB  - The effects of transporting Holstein Friesian bulls (n=72; bodyweight 403+/-3.5
      kg) for 12h by road were examined. Adrenal, haematological and immune responses,
      body temperature and performance were recorded. The animals had been previously
      housed for 96 days at three space allowances (1.2, 2.7 or 4.2m(2) per bull). The
      bulls were allocated to one of two treatments: T (transport for 12h; n=16 per
      space allowance) and C (control; n=8 per space allowance). Basal cortisol plasma
      concentrations and interferon (IFN)-gamma production from cultured lymphocytes
      did not show any statistically significant difference (P>0.05) following the
      housing period. Removing bulls from their home pens and walking them to the pre
      loading crush facility, loading onto the transporter, and unloading following the
      12h road journey, significantly (P<0.001) increased plasma cortisol
      concentration. The bulls housed at 4.2m(2) had greater (P<0.05) plasma cortisol
      concentrations than bulls housed at 1.2m(2) at loading, unloading, or on return
      to the crush holding facility; those housed at 1.2m(2) had greater (P<0.05)
      plasma cortisol concentrations than bulls housed at 2.7 and 4.2m(2) in their home
      pens after transport. There was an increased (P<0.05) plasma cortisol response in
      the T than in the C bulls following adrenocorticotrophic hormone administration.
      Transport significantly reduced (P<0.05) IFN-gamma production, lymphocyte % and
      body weight and significantly increased (P<0.05) neutrophils, eosinophils, packed
      cell volume, red blood cell numbers and haemoglobin. In conclusion, housing bulls
      for 96 days in a range of space allowances did not affect basal cortisol response
      or immune function parameters. Whereas transport increased plasma cortisol and
      reduced the immune response in the short-term, the changes were transient and
      within normal physiological ranges, suggesting that 12h road transport had no
      adverse effect on welfare status over the longer term. Furthermore, transport of
      bulls housed at increased space allowance (4.2m(2)/bull) resulted in a greater
      plasma cortisol response, albeit still within normal physiological range.

PMID- 16632388
TI  - The potential for improving welfare standards and productivity in United Kingdom
      sheep flocks using veterinary flock health plans.
AB  - Data from industry sources detailing variable costs in 2003 revealed that the
      average farmer keeping 1000 lowland ewes in the United Kingdom spent 3500 UK
      pounds annually on veterinary fees and medicines. Despite such expenditure,
      psoroptic mange and cutaneous myiasis are common in the UK, resistance to one or
      more anthelmintic group is not only common but increasing in frequency and
      distribution, and abortion outbreaks caused by Toxoplasma gondii and
      Chlamydophila abortus are frequently reported by veterinary laboratories. Welfare
      concerns also arise from farmers' intransigence towards tail docking and
      castration in lambs (mutilations), reported market forces necessitating long
      distance road transportation to slaughter plants, and an unwillingness to employ
      veterinary surgeons for obstetrical problems. The spread of sheep scab in the UK
      over the past decade illustrates the failure of flock owners to effect
      rudimentary biosecurity and disease control measures. A first step towards
      improving the health and welfare of sheep would be the immediate implementation
      of basic good husbandry practices, including ectoparasiticide treatment for sheep
      scab eradication, prophylaxis for cutaneous myiasis in selected lambs, and
      appropriate vaccination strategies for clostridial diseases and certain abortion
      agents. There would also be money from within current farm expenditure to provide
      veterinary attention for obstetrical problems affecting up to 2% of ewes per
      annum. Planned use of ecto- and endoparasiticides is urgently needed to maintain
      the efficacy of these unique drugs.

PMID- 16632389
TI  - Subarachnoid butorphanol augments lidocaine sensory anaesthesia in calves.
AB  - To determine the efficacy and safety of subarachnoid butorphanol combined with
      lidocaine, six calves were studied. Each calf underwent two treatments, at least
      one week apart, via subarachnoid injection: (1) butorphanol (0.03 mg/kg) plus 2%
      lidocaine (4 mg/kg) and (2) 2% lidocaine (4 mg/kg) alone. Subarachnoid injections
      were performed at the lumbosacral space. Analgesia, motor block, sedation, heart
      rate, arterial blood pressure, respiratory rate, arterial oxygen saturation as
      measured by pulse oximetry, and rectal temperature were compared before and after
      subarachnoid administration of drugs. Subarachnoid administration of the
      butorphanol-lidocaine combination induced bilateral prolonged analgesia extending
      from the coccygeal to the T11-T13 dermatomes in the calves, with minimal sedation
      and severe ataxia. Cardiovascular effects were significant in both treatments:
      heart rate was increased, and there was a minimal decrease in arterial pressure.
      It was concluded that adding a small dose of butorphanol to subarachnoid
      lidocaine in calves is effective and safe.

PMID- 16632390
TI  - The influence of the width of the saddle tree on the forces and the pressure
      distribution under the saddle.
AB  - As there is no statistical evidence that saddle fit influences the load exerted
      on a horse's back, this study was performed to assess the hypothesis that the
      width of the tree significantly alters the pressure distribution on the back
      beneath the saddle. Nineteen sound horses were ridden at walk and trot on a
      treadmill with three saddles differing only in tree width. Kinetic data were
      recorded by a sensor mat. A minimum of 14 motion cycles were used in each trial.
      The saddles were classified into four groups depending on fit. For each horse,
      the saddle with the lowest overall force (LOF) was determined. Saddles were
      classified as "too-narrow" if they were one size (2 cm) narrower than the LOF
      saddle, and "too-wide" if they were one size (2 cm) wider than the LOF saddle.
      Saddles two sizes wider than LOF saddles were classified as "very-wide". In the
      group of narrow saddles, the pressure in the caudal third (walk 0.63 N/cm(2)+/
      0.10; trot 1.08 N/cm(2)+/-0.26) was significantly higher compared to the LOF
      saddles (walk 0.50 N/cm(2)+/-0.09; trot 0.86 N/cm(2)+/-0.28). In the middle
      transversal third, the pressure of the wide saddles (walk 0.73 N/cm(2)+/-0.06;
      trot 1.52 N/cm(2)+/-0.19) and very-wide saddles (walk 0.77 N/cm(2)+/-0.06; trot
      1.57 N/cm(2)+/-0.19) was significantly higher compared to LOF saddles (walk 0.65
      N/cm(2)+/-0.10/ 0.63 N/cm(2)+/-0.11; trot 1.33 N/cm(2)+/-0.22/1.27 N/cm(2)+/
      0.20). This study demonstrates that the load under poorly fitting saddles is
      distributed over a smaller area than under properly fitting saddles, leading to
      potentially harmful pressures peaks.

PMID- 16632391
TI  - An aetiopathological study of chronic bronchopneumonia in lambs in Ireland.
AB  - Chronic bronchopneumonia in lambs, also known as 'atypical' or 'chronic, non
      progressive' pneumonia is a common, frequently sub-clinical disease affecting
      animals under 12-months-old in intensive production systems. Infection with both
      Mycoplasma ovipneumoniae and Mannheimia haemolytica have been implicated in the
      aetiology of this condition and a variety of pulmonary lesions can result. In
      this study, detailed laboratory examination of 30 abattoir-derived lungs with the
      characteristic gross features of atypical pneumonia (AP) was carried out with a
      view to refining and correlating the histopathological and microbiological
      criteria required for the diagnosis of this disease. For the first time a broad
      range of laboratory detection techniques including bacterial and virus isolation,
      fluorescent antibody tests and immunohistochemistry were used in parallel to
      identify potential causative pathogens such as M. ovipneumoniae, M. haemolytica,
      parainfluenza type-3 (PI3) virus and respiratory syncytial virus (RSV) in AP
      lesions. The most consistent finding was the association of gross AP lesions with
      M. ovipneumoniae, identified by either culture or immunohistochemistry in 27
      (90%) of the 30 cases. However the presence M. ovipneumoniae organisms or antigen
      did not consistently correlate with particular histopathological changes.
      Furthermore, peri-airway lymphoid hyperplasia, intra-alveolar exudation and
      nodular 'hyaline scars', which are all previously reported microscopic lesions of
      AP, were not identified in 12 (40%) of the cases and isolation of M. haemolytica
      was over-represented in lungs exhibiting suppurative lesions. These findings
      illustrate the complex aetiopathogenesis of this disease and highlight the
      requirement to use a combination of diagnostic criteria in its laboratory
      diagnosis.

PMID- 16632392
TI  - The effects of the ketogenic diet in refractory partial seizures with reference
      to tuberous sclerosis.
AB  - PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease
      commonly associated with epilepsy refractory to anticonvulsants. Individual
      reports indicate that seizures in children with tuberous sclerosis might benefit
      from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years
      of age in three boys with tuberous sclerosis and refractory partial seizures.
      METHODS: On admission a classical LCT ketogenic diet was initiated and patients
      were followed for 12 months. Antiepileptic drugs were maintained unless adverse
      effects required reduction. RESULTS: Two patients became seizure-free within 2
      months on the diet. In the third patient drop attacks decreased significantly. On
      follow-up the diet was well accepted and without adverse effects. CONCLUSION: The
      ketogenic diet should be considered as a treatment option for children with
      tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data
      support the need for further studies in larger cohorts to confirm the
      effectiveness of the ketogenic diet in this entity.

PMID- 16632393
TI  - Importance of volume limitation for tissue redox status measurements using
      nitroxyl contrast agents: a comparison of X-band EPR bile flow monitoring (BFM)
      method and 300 MHz in vivo EPR measurement.
AB  - Methods proposed for in vivo redox status estimation, X-band (9.4 GHz) electron
      paramagnetic resonance (EPR) bile flow monitoring (BFM) and 300 MHz in vivo EPR
      measurement, were compared. The spin probe 3-carbamoyl-2,2,5,5
      tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was utilized for both methods,
      due to its suitable lipophilicity. EPR signal decay of a nitroxyl spin probe in
      the bile flow and in the liver region (upper abdomen) of several rat groups with
      different selenium status were measured by both the BFM and the in vivo EPR
      method, respectively. The nitroxyl radical clearance measured with in vivo EPR
      method may be affected not only by the redox status in the liver but also by
      information from other tissues in the measured region of the rat. On the other
      hand, the time course of nitroxyl radical level in the bile flow of rats was
      found to be a reliable index of redox status. Measurement site and/or volume
      limitation, which was achieved by the BFM method in this paper, is quite
      important in estimating reasonable EPR signal decay information as an index of
      tissue/organ redox status.

PMID- 16632394
TI  - SideLink: automated side-chain assignment of biopolymers from NMR data by
      relative-hypothesis-prioritization-based simulated logic.
AB  - Previously we published the development of AutoLink, a program to assign the
      backbone resonances of macromolecules. The primary limitation of this program has
      proven to be its inability to directly recognize spectral data, relying on the
      user to define peak positions in its input. Here, we introduce a new program for
      the assignment of side-chain resonances. Like AutoLink, this new program, called
      SideLink, uses Relative Hypothesis Prioritization to emulate "human" logic. To
      address the higher complexity of side-chain assignment problems, the RHP
      algorithm has itself been advanced, making it capable of processing almost any
      combinatorial logic problem. Additionally, SideLink directly examines spectral
      data, overcoming the need and limitations of prior data interpretation by users.

PMID- 16632395
TI  - Flightless rails endemic to islands have lower energy expenditures and clutch
      sizes than flighted rails on islands and continents.
AB  - Data are presented on the standard energetics of six flighted and five flightless
      species of rails (Aves: Rallidae). The factors influencing these data and those
      from three additional species available from the literature, one of which was
      flightless, are examined. Basal rate of metabolism correlates with body mass,
      residency on islands or continents, volant condition, pectoral muscle mass, and
      food habits, but not with climate. The greatest capacity (96.2%) to account for
      the variation in basal rate of metabolism in 15 populations that belong to the 14
      species occurs when body mass, volant condition, and food habits are combined.
      Then flighted species have basal rates that average 1.38 times those of
      flightless species and herbivorous rails have basal rates that are 1.37 times
      those of omnivorous species, which means that, independent of body mass, flighted
      gallinules have basal rates that are 1.9 times those of flightless, omnivorous
      rails. Distribution, pectoral muscle mass, and flight ability cannot be combined
      in the same analysis because they code for similar information. The evolution of
      a flightless condition in rails requires the absence of eutherian predators, but
      has occurred in the presence of marsupial predators. Each of the six studied
      flightless rails independently evolved a flightless condition and a low basal
      rate, whereas the evolution of herbivory and an associated high basal rate
      evolved at least twice in these species. Flightless rails on islands have clutch
      sizes that are only about one-half those of flighted rails living on continents,
      the reduction in clutch size correlating with a reduction in basal rate of
      metabolism. Thermal conductance in rails is correlated with body mass and food
      habits: herbivorous rails had conductances that were 1.43 times those of
      omnivores, i.e., conductances are highest in species with the highest basal
      rates.

PMID- 16632396
TI  - Aspects of placental growth hormone physiology.
AB  - Placental growth hormone (PGH) has been known for 20 years. Nevertheless, its
      physiology is far from understood. In this review, basal aspects of PGH
      physiology are summarised and put in relation to the highly homologous pituitary
      growth hormone (GH). During normal pregnancy, PGH progressively replaces GH and
      reach maximum serum concentrations in the third trimester. A close relationship
      to insulin-like growth factor (IGF)-I and -II levels is observed. Furthermore,
      PGH levels are positively associated to fetal growth. The potential importance of
      growth hormone receptors and binding protein for PGH effects is discussed.
      Finally, the review outlines current knowledge of PGH in pathological
      pregnancies.

PMID- 16632397
TI  - Late recrudescence of Plasmodium falciparum malaria in pregnancy.

PMID- 16632398
TI  - [One case report of anti-JK1 antibody undetected on plasma sample].
AB  - The sensitivity of the detection of irregular antibodies (DIA) is one of the
      fundamental bases of transfusion safety. Its implementation is specified in
      accordance with a very specific framework that allows the use of serum or plasma.
      The case reported here points out a failure to detect irregular antibodies in
      plasma sample. Thus a low intensity anti-JK1 antibody detected and identified in
      serum slipped through unnoticed in plasma. The difficulties to detect and
      identify this antibody, well-known as a deceptive and dangerous one, are being
      discussed in order to better assess the limitations of DIA.

PMID- 16632399
TI  - [Concurrent administration of adjuvant chemotherapy and radiotherapy after breast
      conservative surgery enhances late toxicities].
AB  - PURPOSE: In 1996, a multicenter randomized study comparing after breast
      conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with
      radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen
      patients were included in this trial. After a median follow-up of 6.7 (4.3-9)
      years, we decided to prospectively evaluate the late effects of these two
      strategies. PATIENTS AND METHODS: A total of 297 patients were asked to follow-up
      from the five larger including institutions. Seventy-two percent (214 patients)
      were eligible for late toxicity. After breast-conserving surgery with axillary
      dissection, patients were treated either with sequential treatment with CT first
      followed by RT (arm A) or CT administered concurrently with RT (arm B). In all
      patients, CT regimen combined mitoxantrone (12 mg/m(2)), 5-FU (500 mg/m(2)), and
      cyclophosphamide (500 mg/m(2)), 6 cycles (day 1-day 21). In arm B, patients
      received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to
      5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole
      breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (+/-boost to the
      primary tumour bed). The assessment of toxicity was blinded to treatment and was
      graded by the radiation oncologist according to the LENT-SOMA scale. Skin
      pigmentation was also evaluated using a personal 5-points scoring system
      (excellent, good, moderate, poor, very poor). RESULTS: Among the 214 evaluated
      patients, 107 were treated in each arm. The two populations were homogeneous for
      patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF),
      telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were
      significantly increased in arm B. Twenty patients experienced grade superior or
      equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven
      patients showed grade superior or equal to 2 (T) in arm B and A, respectively
      (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2
      (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade
      superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical
      difference was observed between the two arms concerning grade superior or equal
      to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late
      toxicity. CONCLUSION: Following breast conserving surgery, the concurrent use of
      CT with RT is significantly associated with an increase incidence of grade 2 or
      greater late side effects.

PMID- 16632400
TI  - [Identification of the intercycle FSH signal in urine samples (uFSH)].
AB  - OBJECTIVE: The intercycle FSH signal that initiates follicular recruitment and
      marks the functional onset of the menstrual cycle is of small amplitude and while
      it commonly occurs on cycle day 3, this often varies. Hence, its identification
      and measurement in serum (sFSH) requires serial daily samplings. We attempted to
      determine whether urine measurements of FSH (uFSH) could offer a non-invasive
      alternative, using a model where the intercycle FSH signal is controlled by
      timely use of exogenous E2. PATIENTS AND METHODS: Pilot prospective trial in 21
      infertile women having received E2, from day 25 of the previous cycle until the
      1st Friday after menses. Blood and first void urine samples were collected,
      starting on the last day of E2 (baseline) for assessing FSH and creatinin. A
      sonogram was performed for identification of maturing follicles (>12 mm).
      RESULTS: uFSH and uFSH/Cr showed good correlation with sFSH (R = 0.52 and 0.63, P
      < 0.0001 and P < 0.0001, respectively). In 15/21 patients who had an intercycle
      sFSH elevation, this was confirmed by uFSH elevation, both occurring within 2-4
      days after stopping E2. In all these women, the sonogram showed evidence of
      impending ovulation. The amplitude of the uFSH signal was on average 3 times
      higher than its sFSH counterpart. In 6/21 women, no intercycle FSH elevation was
      detected and no ovulation occurred. DISCUSSION AND CONCLUSION: Our results show
      that the intercycle FSH signal can easily be identified and measured in urine.
      This novel approach permits more precise assessments of ovarian physiology than
      with blood measurements.

PMID- 16632401
TI  - [Reflection on one case of acute peritonitis due to adjustable gastric banding
      during pregnancy].
AB  - Improving the information delivered to pregnant women with adjustable gastric
      banding is desirable. Indeed, we report a case of peritonitis on gastric banding
      due to Klebsiella pneumoniae complicated with fetal death. Then, we discuss the
      specific risks of infection on the gastric band during pregnancy. Although,
      according to the literature, prophylactic fluid removal from the band in early
      pregnancy is not recommended, data about complications in pregnancy due to
      gastric banding are limited.

PMID- 16632402
TI  - Workshop: clinical implications for clinicians treating patients with non
      specific arm pain, whiplash and carpal tunnel syndrome.
AB  - Nerve sheath inflammation without significant axonal degeneration can result in c
      fibres (both axons in continuity and the nervi nervorum) becoming spontaneously
      active and mechanically sensitive. This may help explain the painful responses
      when examining neural dynamics in patients with non specific arm pain, carpal
      tunnel syndrome and arm pain following whiplash injury, when longitudinal nerve
      excursion (measured using ultrasound imaging), appears to be within normal
      ranges. These findings have implications for the clinical examination and
      treatment of these patients groups.

PMID- 16632403
TI  - Study of the mechanisms of uptake of 5-aminolevulinic acid derivatives by PEPT1
      and PEPT2 transporters as a tool to improve photodynamic therapy of tumours.
AB  - Endogenous porphyrin accumulation after administration of 5-aminolevulinic acid
      is employed in photodynamic therapy of tumours. Due to its low membrane
      permeability, esterified 5-aminolevulinic acid derivatives less hydrophilic than
      the parental compound are under investigation. Knowledge of the mechanisms of 5
      aminolevulinic acid derivatives uptake into target cells is essential to
      understand and improve photodynamic therapy and useful in the design of new
      derivatives with better affinity and with higher selectivity for tumour cells in
      specific tissues. The aim of this work was to assess the interaction of 5
      aminolevulinic acid derivatives with the intestinal PEPT1 and renal transporter
      PEPT2 expressed in Pichia pastoris yeasts. We found that Undecanoyl, Hexyl,
      Methyl and 2-(hydroxymethyl)tetrahydropyranyl 5-aminolevulinic acid esters and
      the dendron 3m-ALA inhibited (14)C-5-aminolevulinic acid uptake by PEPT2.
      However, only the Undecanoyl ester inhibited 5-aminolevulinic acid uptake by
      PEPT1. We have also found through a new developed colorimetric method, that Hexyl
      and 2-(hydroxymethyl)tetrahydropyranyl 5-aminolevulinic acid esters display more
      affinity than 5-aminolevulinic acid for PEPT2 whereas none of the compounds
      surpass 5-aminolevulinic acid affinity for PEPT1. In addition, the Undecanoyl
      ester binds with high affinity to the membranes of PEPT2 and PEPT1-expressing
      yeasts and to the control yeasts. The main finding of this work was that some
      derivatives have the potential to improve 5-aminolevulinic acid-based
      photodynamic therapy by increased efficiency of transport into cells expressing
      PEPT2 such as kidney, mammary gland, brain or lung whereas in tissues expressing
      exclusively PEPT1 the parent 5-aminolevulinic acid remains the compound of
      choice.

PMID- 16632404
TI  - The effects of tannin-rich plants on parasitic nematodes in ruminants.
AB  - Apart from the obvious role of plants in herbivore nutrition, they are also a
      rich source of bioactive products that can operate either to the benefit or the
      detriment of grazing animals. Here, we review the available evidence for the
      potential beneficial effects that plant-derived bioactive substances can have on
      gastrointestinal parasites. Tannin-rich plants have attracted most attention for
      their effect on internal nematodes in ruminants. These plants could act through
      direct antiparasitic activity but might also act indirectly by increasing host
      resistance. The effects vary with the species of plant, parasite and host. More
      research is required to understand better the mechanisms of action, and therefore
      make more pertinent use of these bioactive plants in livestock systems.

PMID- 16632405
TI  - Malaria historians: analyze your old slides!

PMID- 16632406
TI  - What are the mechanisms associated with post-ivermectin serious adverse events?

PMID- 16632407
TI  - Lipids of 'Mycobacterium habana', a synonym of Mycobacterium simiae with vaccine
      potential.
AB  - 'Mycobacterium habana' was proposed as a distinct species within the genus
      Mycobacterium; however, it is actually a synonym of Mycobacterium simiae and
      included in the serotype I of this species. The potential use of 'M. habana' as a
      vaccine in both leprosy and tuberculosis has led to the analysis of its lipid
      composition in an attempt to define distinctive markers that could be used in the
      quality control of true strains of this bacterium. Lipids of taxonomic value
      (fatty and mycolic acids) are similar in 'M. habana' and M. simiae; nevertheless,
      they clearly differ on the basis of glycopeptidolipid (GPL) composition. Thus,
      contrary to M. simiae, most strains of 'M. habana' can be defined by the presence
      of three polar compounds, designated GPL-I, GPL-II and GPL-III, easily determined
      by thin-layer chromatography, and characterized, respectively, by the content of
      l-fucose, 2,4-di-O-Me-d-glucuronic acid, and 4-O-Me-d-glucuronic acid, as
      epitopes.

PMID- 16632408
TI  - Lentiviral vectors harboring a dual-gene system allow high and homogeneous
      transgene expression in selected polyclonal human embryonic stem cells.
AB  - Genetic modification of human embryonic stem cells (hESCs) is highly valuable for
      their exploitation in basic science and therapeutic applications. Here we
      developed lentiviral vectors (LVs) constitutively expressing a reporter and a
      selectable marker to enable high and homogeneous transgene expression within
      polyclonal hESCs. LVs carrying GFP and a downstream puromycin resistance gene,
      linked by the encephalomyocarditis virus (EMCV) or poliovirus internal ribosome
      entry sites (IRES), allowed homogeneous GFP expression after antibiotic
      selection. The GFP-expression levels were higher with the EMCV IRES. We also
      developed dual-promoter vectors harboring a reporter and an antibiotic resistance
      gene under the regulation of human EF1alpha and PGK1 promoters, respectively.
      Optimal efficiency was obtained when: (1) the reporter cassette was upstream
      rather than downstream of the selectable marker cassette, (2) the puromycin
      rather than the neomycin resistance gene was used, (3) a 5' deletion (314 bp) was
      created in the PGK promoter, and (4) two copies of a 120-bp element derived from
      the hamster Aprt CpG island were introduced upstream of the EF1alpha promoter. In
      summary, we developed bicistronic and novel dual-promoter LVs that enable high
      and homogeneous expression of transgenes by polyclonal hESCs after antibiotic
      selection. These vectors may provide important tools for basic and applied
      research on hESCs.

PMID- 16632409
TI  - Retrovirus vectors: toward the plentivirus?
AB  - Recombinant retroviral vectors based upon simple gammaretroviruses, complex
      lentiviruses, or potentially nonpathogenic spumaviruses represent relatively well
      characterized tools that are widely used for stable gene transfer. Different
      members of the Retroviridae family have developed distinct and potentially useful
      features related to their life cycle. These natural differences can be exploited
      for specialized applications in gene therapy and could conceivably be combined to
      create future retroviral hybrid vectors, ideally incorporating the following
      features: an efficient, noncytopathic packaging system with low likelihood of
      recombination; serum resistance; an ability to pseudotype with cell-specific
      envelopes; high-fidelity reverse transcription before cell entry; unrestricted
      cytoplasmic transport and nuclear import; an insulated expression cassette;
      specific chromosomal targeting; and physiologic or regulated levels of transgene
      expression. We envisage that, compared to contemporary vectors, a hybrid vector
      combining these properties would have increased therapeutic efficacy and an
      enhanced biosafety profile. Many of the above goals will require the inclusion of
      nonretroviral components into vector particles or transgenes.

PMID- 16632410
TI  - Evaluation and treatment of obesity.

PMID- 16632411
TI  - Rationale and design of the TRANSFACT project phase I: a study to assess the
      effect of the two different dietary sources of trans fatty acids on
      cardiovascular risk factors in humans.
AB  - BACKGROUND: Detrimental effects of consumption of industrial trans fatty acids
      (TFA) from partially hydrogenated vegetable oils (PHVO) on cardiovascular disease
      (CVD) risk factors are well documented. However, very little information is
      available on the effect of natural sources of TFA coming from milk fat, dairy
      products and ruminant meat. In fact, due to the naturally low level of TFA in
      milk fat, it is almost impossible to conduct a clinical trial with a limited
      number of subjects (<200). METHODOLOGY: To compare the effects of industrial and
      natural dietary sources of TFA, two specific test fats have been designed and
      produced. A substantial amount of milk fat (130 kg) enriched in TFA has been
      produced by modification of the cow's diet and selection of cows with the highest
      TFA content. The level obtained was approximately 4- to 7-fold higher than
      typically present in milk fat (approximately 20 instead of 3-6 g/100 g of total
      fatty acids). The control fat is composed of PHVO balanced in saturated fatty
      acids (lauric, myristic and palmitic). Both experimental fats contain about 20
      22% of monounsaturated TFA and the volunteers' daily experimental fat intake (54
      g), will represent about 12.0 g/day of TFA or 5.4% of the daily energy (based on
      2000 kcal/day). These two test fats have been incorporated into food items and
      will be provided to 46 healthy subjects under a randomised, double blind,
      controlled, cross-over design. The primary outcome is high-density lipoprotein
      cholesterol (HDL-C), which is an independent risk factor for CVD. Other
      parameters such as low-density lipoprotein cholesterol (LDL-C), very low-density
      lipoprotein cholesterol (VLDL-C), and HDL-C level and subclasses will be also to
      be evaluated. CONCLUSION: We have shown that it is technically feasible to
      perform a clinical trial on the comparative effects of natural and industrial
      sources of TFA isomers on CVD risk factors. Results are expected by mid-2006.

PMID- 16632412
TI  - Brain-derived neurotrophic factor (BDNF) and food intake regulation: a
      minireview.
AB  - Neurotrophins, and in particular BDNF, play important roles in proliferation,
      differentiation and survival of neurons during development, as well as in the
      synaptic activity and plasticity in many groups of mature neurons. Several lines
      of evidence suggest that BDNF and its high affinity receptor TrkB contribute to
      food intake and body weight control. In rodents, pharmacological treatments with
      BDNF induce reduction in food intake, whereas genetic models with an altered
      BDNF/TrkB signalling display hyperphagia and obesity. Genetic studies in humans
      have shown that mutations in the BDNF or TrkB genes may account for certain types
      of obesity or other forms of eating disorders. Since circulating levels of BDNF
      correlate with eating disorders in humans and peripheral BDNF treatments reduce
      hyperphagia and hyperglycaemia in obese diabetic rodents, an endocrine role of
      BDNF appears plausible and requires further investigation. A central anorectic
      action of BDNF has also been documented, with a primary focus on the hypothalamus
      and a more recent highlight on the brainstem integrator of energy homeostasis,
      the dorsal vagal complex. In this review, we will briefly present neurotrophins
      and their receptors and focus on experimental evidence which point out BDNF as a
      signalling component of food intake regulation, with a particular emphasis on the
      localization of the central anorectic action of BDNF.

PMID- 16632413
TI  - Identifying Mycobacterium tuberculosis complex strain families using
      spoligotypes.
AB  - We present a novel approach for analysis of Mycobacterium tuberculosis complex
      (MTC) strain genotyping data. Our work presents a first step in an ongoing
      project dedicated to the development of decision support tools for tuberculosis
      (TB) epidemiologists exploiting both genotyping and epidemiological data. We
      focus on spacer oligonucleotide typing (spoligotyping), a genotyping method based
      on analysis of a direct repeat (DR) locus. We use mixture models to identify
      strain families of MTC based on their spoligotyping patterns. Our algorithm,
      SPOTCLUST, incorporates biological information on spoligotype evolution, without
      attempting to derive the full phylogeny of MTC. We applied our algorithm to 535
      different spoligotype patterns identified among 7166 MTC strains isolated between
      1996 and 2004 from New York State TB patients. Two models were employed and
      validated: a 36-component model based on global spoligotype database SpolDB3, and
      a randomly initialized model (RIM) containing 48 components. Our analysis both
      confirmed previously expert-defined families of MTC strains and suggested certain
      new families. SPOTCLUST, which is available online, can be further improved by
      incorporating data obtained using additional strain genetic markers and
      epidemiological information. We demonstrate on New York City (NYC) patient data
      how the resulting models can potentially form the basis of TB control tools using
      genotyping.

PMID- 16632414
TI  - Anti-inflammatory therapy in the neonatal intensive care unit: present and
      future.
AB  - Inflammation has been linked to numerous adverse outcomes in newborns. This paper
      reviews several major sources of inflammation, methods to reduce exposure,
      current anti-inflammatory drug therapy and future research directions. The first
      major source of inflammation--chorioamnionitis--is often present long before
      delivery; postnatal interventions may not alter outcomes. Reducing the exposure
      of preterm infants to postnatal inflammatory stimuli such as mechanical
      ventilation and sepsis may be more effective than anti-inflammatory drug therapy
      in improving outcomes. If anti-inflammatory drug therapy is considered necessary,
      the only drug currently proven to decrease extubation failure and
      bronchopulmonary dsyplasia (BPD) is dexamethasone, which is associated with
      numerous side effects. Erythromycin treatment of Ureaplasma urealyticum has been
      ineffective in reducing BPD; are trials of azythromycin planned. Research may
      improve future outcomes by tailoring glucocorticoid dosage, duration and
      formulation in targeted populations and by developing agents to inhibit specific
      pro-inflammatory mechanisms.

PMID- 16632415
TI  - Long-term consequences of pain in human neonates.
AB  - The low tactile threshold in preterm infants when they are in the neonatal
      intensive care unit (NICU), while their physiological systems are unstable and
      immature, potentially renders them more vulnerable to the effects of repeated
      invasive procedures. There is a small but growing literature on pain and tactile
      responsivity following procedural pain in the NICU, or early surgery. Long-term
      effects of repeated pain in the neonatal period on neurodevelopment await further
      research. However, there are multiple sources of stress in the NICU, which
      contribute to inducing high overall 'allostatic load', therefore determining
      specific effects of neonatal pain in human infants is challenging.

PMID- 16632416
TI  - Evolution in brachytherapy.

PMID- 16632417
TI  - Tobacco, 500 years of smoke.

PMID- 16632418
TI  - GEICAM. Spanish Breast Cancer Research Group.

PMID- 16632419
TI  - From the bench to the bed: individualizing treatment in non-small-cell lung
      cancer.
AB  - At the time of diagnosis, half of lung cancer patients have advanced incurable
      disease. Different chemotherapy combinations--with or without targeted therapies-
      yield similar results in spite of the continuous efforts of clinicians. However,
      molecular biological studies have already shed a great deal of light on the
      existence of multiple genetic aberrations that can be useful for customizing
      treatment. mRNA transcripts involved in DNA repair pathways, such as ERCC1 and
      BRCA1, confer selective resistance to cisplatin or taxanes. Polymorphisms in DNA
      repair genes and methylation of checkpoint genes in circulating serum DNA could
      become important predictive markers of survival to certain cisplatin-based
      regimens. EGFR tyrosine kinase mutations are the crux of targeted therapies.

PMID- 16632420
TI  - Cell signalling: growth factors and tyrosine kinase receptors.
AB  - The mitogenic signaling in mammalian cells is carried out mainly by growth
      factors that interact with receptors localized at the plasma membrane. Most of
      these receptors have a tyrosine kinase activity domain that is localized at the
      cytoplasmic region of the molecule. The interaction of the growth factors with
      the receptors, besides inducing the kinase activity of the receptor, activate
      signaling pathways the alter gene expression patterns and induce mitogenesis, or
      if deregulated are related to cancer. Among these receptors ERBB, VEGF, PDGF and
      IGF are attractive targets for directed therapies. ERBB receptors are frequently
      involved in the production of many types of cancers. Both, the over-expression of
      the growth factor and the receptor, besides mutations at the cytoplasmic tyrosine
      kinase domain contribute to constitutive signaling in human cancer. VEGF has a
      pivotal role in maintaining the tumor growth by facilitating growth of new blood
      vessels. Therefore, inhibition of tumor growth targeting of the tumor
      vasculature, by interfering with the activity of VEGFr is now a real alternative
      in combinatorial therapies. PDGF is a growth factor involved in growth of
      connective tissue and wound healing. Activating mutations of PDGFr have been
      found in gastrointestinal tumors and the autocrine signaling maintained by this
      receptor have been described in many tumors. Imatinib, and inhibitor of the
      tyrosine kinase activity of Bcr-Abl targets also the kinase of the PDGFr. Finally
      IGF-I an II have an important antiapoptotic and pro-mitogenic role in most
      tumors. Different inhibitors are now under clinical studies for the use in
      combination of chemotherapeutic drugs in the treatment of different tumors.

PMID- 16632422
TI  - Informed consent and sedation.
AB  - The concept of autonomy was not included in the Hippocratic Oath. Nowadays the
      principle of respect for autonomy is an important right. The basic paradigm of
      autonomy in health-care, politics and other contexts is expressed as informed
      consent. In the palliative-care setting, there can be some difficulties in
      getting informed consent, especially at the end-of-life stage. Can it be good for
      the patient, always? Could there be some exceptions? At the time of agonizing
      pain, getting informed consent could become an additional burden for the patient.
      This present article attempts to shed light on this issue. In our experience, it
      is not necessary to obtain written consent for a patient who has already
      expressed his priorities in advance. We believe that this is a good stance for
      patients as well as doctors.

PMID- 16632421
TI  - The impact on oncology of the interaction of radiation therapy and radiobiology.
AB  - The quantitative analysis of the cell dose-survival curves, the randomness of
      cell killing by radiation, the probabilistic basis of the response to irradiation
      of tumors and normal tissues, the understanding of the biological mechanisms
      underlying to this response, the rationale for dose-time and fractionation in
      radiotherapy, the introduction of the concepts of tumor control probability (TCP)
      and biologically effective dose (BED), the relationships TCP-dose, BED-alpha/beta
      BED-fraction size and BED-treatment time, the problems associated with the
      accelerated regeneration of surviving tumor clonogens during the course of
      fractionated radiotherapy, the new demands of knowledge on oncology and radiation
      biology derived from heterogeneous dose distributions in conformal radiation
      therapy programs and the definition of the biological basis of normal tissues
      tolerance to reirradiation are, probably, the most important contributions of
      radiobiology to clinical radiotherapy in the last twenty five years. Radiotherapy
      is today a scientific discipline based on the interplay of mathematics, physics,
      biology and oncology. The knowledge of the basic concepts of radiobiology is
      essential for daily radiotherapy practices and for all oncologists. The most
      efficient use of multimodality treatments in cancer therapy cannot be done
      without a clear understanding of these principles.

PMID- 16632423
TI  - Guides for adjuvant treatment of colon cancer. TTD Group (Spanish Cooperative
      Group for Gastrointestinal Tumor Therapy).
AB  - The choice of the most suitable chemotherapy schedule for the adjuvant treatment
      of colon cancer has been reviewed by the TTD group, as well as the principles of
      risk assessment for patients with stage II disease. In the light of data now
      available, oxaliplatin- based schedules (FOLFOX4 or FLOX) are recommended.
      Alternatives in special situations are monotherapy with capecitabine, UFT/LV, or
      5- FU/LV in infusion. In patients with stage II disease, the indication of
      chemotherapy must be individualized and based on the patient's risk of recurrence
      (perforation, obstruction, peritumoral lymphovascular involvement, poorly
      differentiated histology, number of lymph nodes examined < or = 11, pre-surgical
      CEA), and comorbidities that can compromise the safety of treatment or survival
      of the patient.

PMID- 16632424
TI  - Diagnostic efficiency of sestamibi gammagraphy and Doppler sonography in the
      preoperative assessment of breast lesions.
AB  - INTRODUCTION: It would be desirable to have preoperative methods that allow an
      adequate selection of patients with breast lesions to rule out breast cancer. The
      aim of the present study is to evaluate the efficiency of preoperative Sestamibi
      gammagraphy and Doppler sonography regarding the differential diagnosis of
      malignancy in breast lesions. MATERIAL AND METHODS: A prospective observational
      study was conducted on 88 consecutive patients with breast lesions. All the
      patients underwent preoperative Doppler sonography with an echo-enhancing agent
      and Sestamibi gammagraphy. All the patients had histopathological study of the
      surgical specimen to compare with the result of the preoperative techniques.
      These comparisons were done both for the overall series and separately for
      palpable and non-palpable lesions. RESULTS: In the overall series results, both
      tests separately and the two combined, are related significantly to the malignant
      histological diagnosis (p < 0.001). In palpable lesions, there is a considerable
      increase in sensitivity, and especially in specificity, attaining 100%, with the
      combination of both tests. In non-palpable lesions, a relationship was only found
      between the results of the Sestamibi gammagraphy and the malignant histological
      diagnosis (93.3%; p < 0.05). CONCLUSIONS: Sestamibi gammagraphy and Doppler
      sonography are two efficient exploratory techniques in the preoperative
      assessment of malignancy in breast lesions, especially for palpable lesions, and
      this efficiency is greater when they are combined.

PMID- 16632425
TI  - Prognostic value of the interpectoral lymph nodes in breast cancer. A 20-year
      survival study.
AB  - INTRODUCTION: The indication and extent of axillary lymph node dissection in
      breast cancer remains open to controversy. MATERIALS AND METHOD: In this context,
      a 20-year survival study has been made of 1600 breast cancer patients subjected
      during surgical treatment to systematic dissection of the acromiothoracic
      vascular pedicle together with the accompanying lymph nodes (Rotter and Grossman
      interpectoral lymph node groups). An anatomical study of these nodes was also
      conducted in 100 necropsies, with the evaluation of 200 acromiothoracic vascular
      pedicles. RESULTS: The interpectoral lymph nodes were anatomically present in 42%
      of the necropsies and in 35.1% of the patients subjected to surgery. The
      prognosis was much worse in cases of neoplastic infiltration of the interpectoral
      lymph nodes (Kaplan-Meier survival study), regardless of the influence of other
      prognostic factors. CONCLUSIONS: In view of the results obtained, the designation
      of grade N3 of the TNM classification is proposed for malignancies with positive
      interpectoral lymph node infiltration.

PMID- 16632426
TI  - Craniofacial resection for sinunasal tumors.
AB  - INTRODUCTION: Malignant sinonasal tumors are very rare in Mexico. They ussually
      present as advanced disease because it is extremely difficult to make an early
      diagnosis; in addition, its treatment is complicated by a variety of lesions.
      Surgical resection remains the mainstay of treatment, but its relative
      therapeutic value compared with alternative treatments is controversial.
      OBJECTIVE: We undertook a retrospective analysis in order to evaluate results of
      craniofacial resections for sinonasal tumors. MATERIALS AND METHODS: A total of
      20 patients, 11 men and 9 women were considered, median age was 49 years (18-74).
      Eleven had received previous treatment elsewhere. In 13 patients tumor was
      limited to maxillo-ethmoid complex, but in 6 cases tumor involved anteroinferior
      aspect of sphenoid sinus, in 7 extended to the orbit, in 3 to dura and two to the
      brain. One had cervical metastases. Median tumoral size was 5.8 cm (1-10).
      RESULTS: Overall complication rate was 50%. Major surgical complications occurred
      in 4 patients (20%): one patient developed isolated cerebrospinal fluid leakage
      (CEFL), 1 developed deterioration of mental status, and two developed meningitis
      associated with CEFL. Late complications occurred in 30% of the patients. There
      was not any operative death. Eleven patients received postoperative radiotherapy.
      Fifteen patients recurred. There were 11 local relapses, although one associated
      with a regional relapse, and another with regional and distant relapse. There
      were four isolated regional fails and six isolated distant failures. Three year
      overall survival was 65%, and 3-year disease free survival was 50%. Patients
      without previous treatment median survival was 28.3 months, meanwhile with
      previous treatment was 18.2 months. CONCLUSIONS: Craniofacial resection is a safe
      and valuable tool in the treatment of advanced sinonasal tumors involving cranial
      base.

PMID- 16632427
TI  - Usefulness of 18-fluorodeoxyglucose positron emission tomography in the
      evaluation of tumor cardiac thrombus from renal cell carcinoma.
AB  - PURPOSE: Retrospectively analysed our experience in Renal Cell carcinoma (RCC)
      patients studied with 18-Fluorodeoxyglucose Positron Emission Tomography (FDG
      PET) to rule out the incidence and clinical impact of heart metastases. MATERIAL
      AND METHODS: In two years, 37 patients with RCC were studied with FDG PET. 10
      were studied for initial staging and 27 patients were evaluated for suspected
      recurrence or re-staging. RESULTS: In two patients (5%), PET scan showed
      pathological focal uptake in myocardium. On the bases of this finding, MRI was
      performed visualizing a myocardial mass in both lesions and confirmed by
      histology in one of them. The hypothesis of prolepses of the tumour by thrombus
      in RCC patients justified the surgery. CONCLUSION: Whole-body FDG PET in RCC
      patients could help to diagnose cardiac metastasis, and allows the possibility of
      therapeutic surgery, due to the thrombus significance of heart involvement.

PMID- 16632428
TI  - Malignant mixed Mullerian tumors.
AB  - Malignant mixed Mullerian tumours (MMMTs) are rare neoplasms, highly aggressive
      and with an extremely poor prognosis, usually arising in elderly postmenopausal
      women and presenting at an advanced stage. MMMTs derive from the mullerian
      mesodermus that differentiates in epithelial and stromal elements, both malignant
      elements. The clinic pathological features of 3 uterine MMMTs are reported here.
      The patients ranged in age from 25 to 69 years. The initial manifestations were
      mainly bloody discharge, abdominal pain and increase of the volume of the uterus.
      Treatment in 2 patients was hysterectomy with double ooforectomy, and resection
      of the pelvic mass was the treatment in the third case. Adjuvant radio
      chemotherapy was administrated in 2 of the 3 cases. Follow-up revealed recurrent
      pelvic tumour in 1 patient at 59 months, and breast metastases at 20 months in
      the second one. Because of the high incidence of recurrence and poor prognosis of
      these tumours, they should be studied and managed by a multidisciplinary team
      composed by surgeons, oncologists, radiotherapists and pathologists.

PMID- 16632429
TI  - Bronchiolitis obliterans organizing pneumonia simulating progression in
      bronchioloalveolar carcinoma.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathologic
      syndrome with characteristic features. The diagnosis of BOOP requires the
      presence of a combination of pathological, clinical, and radiological features.
      We report the case of a lung cancer patient with bronquiloalveolar carcinoma
      (BAC) presenting with BOOP after chemotherapy with docetaxel and gemcitabine
      producing severe respiratory insufficiency, and simulating a progression of the
      tumor.

PMID- 16632430
TI  - Subcutaneous metastasis as the first manifestation of a solid-pseudopapillary
      tumor of the pancreas.

PMID- 16632432
TI  - The cancer strategy in the art of war.

PMID- 16632433
TI  - Spanish Cooperative Group for Gastrointestinal Tumor Therapy.

PMID- 16632434
TI  - Molecular biology of breast cancer.
AB  - Although Breast Cancer (BC) has been considered for many years as a single entity
      with a common management and treatment, it is actually a extremely heterogeneous
      disease which includes at least 4 or 5 very different subtypes. The first step in
      the recognition of the heterogeneity of BC was the demonstration of the presence
      of functional hormonal receptors (HR) in nearly two thirds of breast cancer
      specimens. This finding, which established a first classification of BC in two
      clear subtypes (HR-positive and HR-negative) was followed by the demonstration of
      many other differential features. The her2/neu gene alteration, present in nearly
      20% of BC tumors, is probably the most relevant of them, but certainly not the
      only one. The development of new technologies and, in particular, the use of
      complementary DNA (cDNA) microarrays will allow us now the simultaneous analysis
      of thousands of genes and the establishment of new, more refined BC subtypes
      based on gene expression profiles/genetic fingerprints. This review discusses the
      practical applications of molecular analysis of BC, which can be classified in
      four categories: 1. Establishment of a new molecular taxonomy of breast cancer.
      2. Definition of prognostic factors/prognostic indexes based on molecular/genetic
      peculiarities. 3. Prediction of response to diverse antitumoral treatments. 4.
      Identification of molecular targets that allows the development of new tailored
      antitumor treatments.

PMID- 16632435
TI  - Mediterranean diet, olive oil and cancer.
AB  - Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating
      evidence suggests that it may have a potential role in lowering the risk of
      several types of cancers. The mechanisms by which the cancer-preventing effects
      of olive oil can be performed, however, are not known. We recently hypothesized
      that a novel molecular explanation concerning the anti-cancer actions of olive
      oil may relate to the ability of its monounsaturated fatty acid (MUFA) oleic acid
      (OA; 18:1n-9) to specifically regulate cancer-related oncogenes. Supporting our
      hypothesis, exogenous supplementation of cultured breast cancer cells with
      physiological concentrations of OA was found to suppress the overexpression of
      HER2 (Her-2/neu, erbB-2), a well-characterized oncogene playing a key role in the
      etiology, progression and response to chemotherapy and endocrine therapy in
      approximately 20% of breast carcinomas. OA treatment was also found to
      synergistically enhance the efficacy of trastuzumab, a humanized monoclonal
      antibody binding with high affinity to the ectodomain (ECD) of the Her2-coded
      p185(HER2) oncoprotein. Moreover, OA exposure significantly diminished the
      proteolytic cleavage of the ECD of HER2 and, consequently, its activation status,
      a crucial molecular event that determines both the aggressive behavior and the
      response to trastuzumab of Her2-overexpressing breast carcinomas. Our most recent
      findings further reveal that OA exposure may suppresses HER2 at the
      transcriptional level by up-regulating the expression of the Ets protein PEA3 -a
      DNA-binding protein that specifically blocks HER2 promoter activity- in breast,
      ovarian and stomach cancer cell lines. This anti-HER2 property of OA offers a
      previously unrecognized molecular mechanism by which olive oil may regulate the
      malignant behavior of cancer cells. From a clinical perspective, it could provide
      an effective means of influencing the outcome of Her-2/neu-overexpressing human
      carcinomas with poor prognosis. Indeed, OA-induced transcriptional repression of
      HER2 oncogene may represent a novel genomic explanation linking "Mediterranean
      diet", olive oil and cancer as it seems to equally operate in various types of
      Her-2/neu-related carcinomas.

PMID- 16632436
TI  - Influence of hemoglobin levels on survival after radical treatment of esophageal
      carcinoma with radiotherapy.
AB  - INTRODUCTION: The objective was to investigate the possible prognostic value of
      blood hemoglobin concentration in the outcome of radical treatment for locally
      advanced esophageal carcinoma. MATERIALS AND METHOD: This was a retrospective
      analysis of data for 85 patients treated for locally advanced esophageal
      carcinoma between January 1991 and January 1997 with chemoradiotherapy alone or
      as neoadjuvant therapy. All patients received chemotherapy (4 cycles of cisplatin
      100 mg/m2 on day 1, and continuous infusion 5-fluorouracil 1 g/m2 per day on days
      1-5) with concomitant radiotherapy (40 Gy at 2 Gy/session to the esophageal tumor
      and mediastinum). The response was evaluated after 4 weeks. 69 patients continued
      to receive chemoradiotherapy only to a total dose of 60-64 Gy to the esophageal
      tumor with a 2-cm margin. Sixteen patients underwent radical surgery. Hemoglobin
      levels were measured before combined treatment in all patients. The prognostic
      value of hemoglobin concentration was analyzed statistically, along with other
      patient-, tumor- and treatment-related factors. RESULTS: Mean follow-up time: 82
      months (range 60- 99 months). Chemoradiotherapy was followed by an overall
      clinical response of 69.4%, with complete clinical response in 24.7% of the
      patients. Mean survival time was 12 months, and overall likelihood of survival
      after 3 years was 13%. Mean time to progression: 5 months. Median survival time
      was 12 months in the 69 patients who underwent chemoradiotherapy alone, and 26
      months in patients who underwent radical surgery. Univariate analysis showed a
      hemoglobin value of > 13 g/dl to be a prognostic factor for better survival,
      along with performance status according to the ECOG classification, weight loss <
      10%, tumor stage, tumor length, and complete response to chemoradiotherapy.
      Multivariate analysis showed that only hemoglobin concentration was an
      independent prognostic factor: for each unit increase in hemoglobin level, the
      risk of death from esophageal carcinoma decreased by 5%. In the subgroup of
      patients who did not undergo surgery, hemoglobin concentration was also an
      independent prognostic factor along with complete clinical response. CONCLUSIONS:
      As found for other solid tumors, hemoglobin level was a determining factor in the
      prognosis for treatment outcome in patients with esophageal carcinoma. Our
      findings require confirmation in randomized studies and further documentation of
      the probable benefits of correcting hemoglobin levels.

PMID- 16632437
TI  - Systematic review of case reports concerning adults suffering from neutropenic
      enterocolitis.
AB  - INTRODUCTION: Neutropenic enterocolitis (NEC) is a well recognised clinical
      pathological and life-threatening complication in patients suffering from several
      conditions, including solid and haematological malignancies or aplastic anaemia.
      OBJECTIVE: This review was aimed at evaluating overall NEC mortality rate,
      describing clinical diagnostic findings and therapeutical interventions reported
      in the literature and generating a hypothesis regarding factors influencing
      mortality and surgical intervention. MATERIALS AND METHODS: An advanced search
      was made in Medline, Embase, Lilacs and Google. Additional strategies included
      manual search of specific journals. Reports were considered if they described
      case definition, inclusion and exclusion criteria. RESULTS: 275 cases were
      selected; 109 were from individual data and 40 from grouped data. Comparing data
      between case reports and case series revealed no significant differences related
      to mortality, surgical intervention, sex or age. Higher mortality (chi2 = 7.51 p
      = 0.006) was found in women (50%) compared to men (28%). No significant
      difference was found between antibiotic combinations and mortality (chi(2) =
      12.85 df 13 p = 0.45). Mortality (chi2 = 3.89 df 1, p = 0.049), surgical
      intervention (chi2 = 7.64 df 1, p = 0.006) and duration of diarrhoea (chi2 = 4.71
      df 1, p = 0.043) were significantly different in 26.4% of individuals using
      antifungal agents; death occurred in 81% of patients! who did not receive such
      medication compared to 19% individuals reported as being treated with antifungal
      agents. CONCLUSION: The current evidence suggests that antifungal agents should
      be used early in patients suffering from NEC. However, this hypothesis must be
      evaluated in multi-centric, randomised controlled trials.

PMID- 16632438
TI  - Survival in extra-orbital metastatic retinoblastoma:treatment results.
AB  - INTRODUCTION: Retinoblastoma (RB) is the most frequent malignant eye tumor in
      childhood. In developing countries advanced stages are common. The purpose of
      this paper is to present our 21-year clinical experience with metastatic extra
      ocular RB patients treated with 5 different chemotherapy schemas at a single
      Mexican Pediatric referral center. MATERIALS AND METHODS: A retrospective
      analysis was carried out reviewing the clinical characteristics of patients with
      metastatic RB. The information analyzed included the delay in diagnosis after
      first symptoms, age, sex, ocular staging, and anatomic site of metastases,
      treatment scheme, initial response and status at the last contact or date of
      death. RESULTS: Eighty-one patients were included; age range was from 3 to 80
      months. The most common site of metastasis was central nervous system (83.9%).
      From those patients treated with chemotherapy (n = 74), 89.2% presented a
      complete initial response (n = 66). Early mortality occurred in 7 cases before
      any treatment. Fifty-six received treatment and died with progressive disease.
      All patients without radiotherapy died with tumor activity (n = 15). The use of
      cisplatin was related with longer disease free intervals; no other variable was
      related with survival. Four patients were alive and disease free at 33 to 144.3
      months of follow up from diagnosis. The prevalent cause of death was tumor
      progression. CONCLUSIONS: In our experience, metastatic RB has a very high
      mortality rate in spite of the use of different chemotherapy regimens.

PMID- 16632439
TI  - Treatment of childhood diffuse brain stem tumors: comparison of results in
      different treatment modalities.
AB  - BACKGROUND: Diffuse brainstem tumors in children are rare and its treatment is
      controversial. Although radiotherapy (RT) used to be the treatment of choice,
      results remained unsatisfactory. The association of RT with other therapies is
      common, but lacks scientific data regarding its efficacy. Comparison of results
      of irradiation alone versus combined treatment modalities is crucial in improving
      survival. METHOD: The authors reviewed twenty-four patients with diffuse
      brainstem tumors, with mean age of 7 years, treated from December 90 to November
      99, at the University of Sao Paulo, Brazil. These patients were subdivided in
      four groups according to the treatment option at the onset of symptoms. Four
      patients were treated with radiation alone (total dose of 50 Gy to 62.4 Gy), 6
      patients with chemotherapy and radiation, 8 with tamoxifen and radiation and 6
      with tamoxifen, radiation and chemotherapy. The results of the different groups
      were them compared. FINDINGS: Clinical response was observed in 83.3% of our
      children, briefly followed by progressive disease. Mean survival was 17 months
      with no statistically significant differences among the groups. Four patients
      were alive at the end of the study, with a mean survival of 32.4 months, all of
      them received combined therapy, but with no statistically significant
      differences. CONCLUSIONS: Neither the association of radiation therapy with
      chemotherapy, tamoxifen nor both have showed survival improvement. The prognosis
      of these patients remains very poor and only investigational trials would justify
      a highly aggressive approach.

PMID- 16632440
TI  - Brain metastases in metastatic breast cancer patients receiving trastuzumab-based
      therapies.
AB  - INTRODUCTION: CNS metastases mean a great challenge. It has been suggested that
      the brain metastases incidence could be high in metastasic breast cancer patients
      receiving trastuzumab based-therapies. MATERIAL AND METHODS: We performed a
      descriptive analysis of our experience in this setting. 86 patients met the
      criteria (From Oct/99 to Oct/03). RESULTS: CNS progression occurred in 17
      patients (19.5%). Mean age of CNS progression disease patients was 45.4 years
      while mean age for all the patients was 50.5 years. Response rate for the entire
      group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab
      based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median
      time from the start of trastuzumab therapy up to the CNS progression was 10
      months. OS was 23.4 weeks. CONCLUSIONS: The incidence of CNS involvement is high
      in young metastasic breast cancer women responding to trastuzumab-based
      therapies. This may lead to prophylactic cranial irradiation strategies or to the
      early detection in asymptomatic patients to improve surgery or radiosurgery
      results in these patients.

PMID- 16632441
TI  - Primary carcinoid tumour of the pancreas.
AB  - Pancreatic carcinoid tumours are extremely infrequent. Usually, the biological
      behaviour is indolent and diagnosis is late and often casual. We present the case
      of a patient initially diagnosed as having liver metastasis of unknown origin.
      PET identified a primary pancreatic site and the initial histologic diagnosis was
      adenocarcinoma. Following an uncertain response to chemo- and radio-therapy the
      repeat histologic assessment indicated a carcinoid tumour of the pancreas. After
      complete surgical resection and liver transplantation, patient remains free of
      disease. CONCLUSIONS: The co-existence of several diseases with similar morpho
      structural features makes diagnosis complicated. PET is of uncertain use in the
      evaluation of carcinoid tumours, and is considered inferior to 111Indium
      octreotide scan. The only curative treatment is surgical resection, with liver
      transplantation as a valid option in the treatment of these tumours.

PMID- 16632442
TI  - Breast metastases as the first sign of recurrence of a cutaneous melanoma.
AB  - Malignant melanoma is the most rapidly increasing cancer in the world. Metastatic
      disease occurs in 20% of patients, and prognosis in these cases is poor. We
      report the case of a woman who presented breast metastasis as the first sign of
      recurrence of a melanoma.

PMID- 16632443
TI  - Life-threatening adverse drug reaction to paclitaxel. Postmarketing surveillance.
AB  - The mechanism of action of hypersensitivity reactions from paclitaxel has not
      been fully understood. It has not even been defined if they are secondary to
      paclitaxel, its vehicle or the premedication. Postmarketing pharmacovigilance is
      predominantly based on spontaneous reporting. These reports albeit biased and
      incomplete serve to detect previously unrecognised adverse events. We report a
      life threatening adverse event related to paclitaxel without any evidence of
      histamine release. It consisted of a cardiac arrest probably secondary to
      bradiarrhythmia or branch block.

PMID- 16632444
TI  - Determination of the physicochemical properties of pyronaridine - a new
      antimalarial drug.
AB  - The physicochemical properties of pyronaridine, a new antimalarial drug, have
      been determined for the first time in this study, since these parameters are
      comprehensively not available in literature. UV-Vis spectral analysis of both
      pyronaridine and its tetraphosphate salt were carried out in various solvents, in
      addition to solubility of the two drugs in these solvents. Partition coefficient
      was done in n-octanol-water mixture using the Leo-Hansch method as well
      hydrophobicity index determination. pKa determination was carried out on the
      tetraphosphate. UV-Vis spectral characteristics showed that both the base and the
      tetraphosphate salt have significant light absorption in the range 190-380 nm.
      Solubility in different solvents revealed that pyronaridine base is sparingly
      soluble in chloroform (1.34%) while it is slightly soluble in methanol (0.29%)
      and ethanol (0.42%) and very slightly soluble in octanol and distilled water. The
      tetraphosphate salt was sparingly soluble in water (1.46%) while it is only very
      slightly soluble in other solvents. The higher aqueous solubility of the salt was
      further revealed by a greater Rm value on extrapolation to 100% water
      concentration in hydrophobicity index determination. Log P value determination
      showed that the base {log P of 0.26+/-0.02} is more liposoluble than the salt
      {log P of - (1.240.21)}. Four prominent pKa values were obtained for the
      tetraphosphate titrated which when extrapolated to the base gave values of 7.08+/
      0.05, 7.39+/-0.05, 9.88+/-0.05 and 10.30+/-0.10. The results should guide in
      formulation of appropriate dosage forms to improve bioavailability of the drug
      especially from oral routes.

PMID- 16632445
TI  - Effect of processing variables on micro particulate system of aceclofenac.
AB  - Microparticulate systems of aceclofenac were prepared by modified solvent
      evaporation method using different variables such as polymer (cellulose acetate):
      drug ratios (1:9, 1:6, 1:3, and 1:1), agitation speeds (500-1,500 rpm) and
      stirring time (5-15 min). The effects of processing variables were evaluated by
      microparticle size and entrapment efficiency. The average microparticle size
      increases from 80.2+/-1.45 to 97.3+/-2.06 microm with increase in the polymer
      concentration while reduces with increase in agitation speed and stirring time;
      and at the higher speed gives irregular shape of particles. The highest
      entrapment efficiency, size uniformity, angle of repose (23.6+/-0.3 degree) and
      compressibility index (13.8+/-0.7%) of microparticles were found with 1:6
      (polymer: drug ratio), at 1,000 rpm and 10 min stirring time among all
      microparticles. The in-vitro drug release study was carried out with prepared
      microcapsules (AC-1 to AC-4) of various polymer concentrations and optimized
      processing variables and compared with conventional and SR tablets. The
      conventional tablet and SR tablet releases maximum drug within 3 and 6h
      respectively while microparticulate system releases more than 12h. All
      formulations followed first order release kinetic and diffusion controlled drug
      release.

PMID- 16632446
TI  - Relationship of brain tryptophan and serotonin in improving cognitive performance
      in rats.
AB  - Brain function can be affected by the availability of dietary precursors of
      neurotransmitters. The diet induced increase in tryptophan (TRP) availability has
      been shown to increase brain serotonin synthesis and various related behaviors.
      Evidence shows that TRP and serotonin (5HT; 5 Hydroxytryptamine) play a
      significant role in memory function. Enhanced brain serotonin activity has been
      shown to improve cognitive performance in animals and human whereas decreasing
      brain 5HT levels by acute TRP depletion has been shown to impair cognition. A
      number of methods have been used for the assessment of memory in animals. In the
      present study, the radial arm maze and the passive avoidance was used for the
      assessment of memory in rats following long-term TRP administration. TRP at doses
      of 50 and 100 mg/kg body weight was orally administered for 6 weeks. The present
      study shows a significant improvement in memory of rats following both doses of
      tryptophan. Plasma TRP, brain TRP, 5HT and 5 hydroxy indol acetic acid (5HIAA)
      levels were increased significantly following administration of TRP. The results
      of the present study suggest that increase in brain 5HT metabolism following long
      term TRP administration may be involved in enhancement of memory.

PMID- 16632447
TI  - Interactions between sparfloxacin and antacids - dissolution and adsorption
      studies.
AB  - Sparfloxacin is a broad-spectrum oral fluoroquinolone antimicrobial agent with a
      long elimination half-life, extensively used against both Gram-positive as well
      as Gram-negative microorganism. Concurrent administration of antacids and
      sparfloxacin decreases the gastrointestinal absorption of sparfloxacin and
      therapeutic failure may result. The present study was designed to evaluate the
      influence of some antacids on the availability of sparfloxacin. The release of
      sparfloxacin from tablets in the presence of antacids like sodium bicarbonate,
      calcium hydroxide, calcium carbonate, aluminum hydroxide, magnesium hydroxide,
      magnesium carbonate, magnesium trisilicate and magaldrate has been studied on BP
      2003 dissolution test apparatus. These studies were carried out in simulated
      gastric and intestinal juices for three hours at 37 degrees C. The results
      confirmed that the dissolution rate of tablets was markedly retarded in the
      presence all of antacids studied, whereas magaldrate and calcium carbonate
      exhibited relatively higher adsorption capacities in simulated gastric juice and
      magnesium trisilicate and calcium hydroxide in simulated intestinal juice.

PMID- 16632448
TI  - Modification of drug release from acetaminophen granules by melt granulation
      technique - consideration of release kinetics.
AB  - Acetaminophen granules have been formed by a melt granulation process with the
      objective of retarding drug release for prolonged action formulations. The waxes
      used were goat wax, carnuba wax and glyceryl monostearate. In the melt
      granulation procedure, acetaminophen powder was triturated with the melted waxes
      and passed through a sieve of mesh 10 (aperture size 710 microm). The content of
      wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were
      also formed by the convectional method of wet granulation with starch mucilage
      (20%w/w). The granules were subjected to in-vitro drug release tests. The release
      data were subjected to analysis by three different well-established mathematical
      models (release kinetics) namely, - zero order flux, first order, and the Higuchi
      square root of time relationship. The convectional granules exhibited an initial
      zero order flux (first 55%) followed by a first order release profile (the
      remaining 45%). The pattern of drug release from the melt granulations was
      consistent with the first order kinetic and the Higuchi square root of time
      relationship, indicating a diffusion-controlled release mechanism. The first
      order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1).
      After melt granulation (wax content, 20%w/w) the rate constants dropped
      drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax),
      and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes
      were equivalent in retarding drug release from the melt granulations.

PMID- 16632449
TI  - In vitro availability of metformin in presence of h(2) receptor antagonists.
AB  - Metformin is a guanidine derivative used for the treatment of NIDDM. As it is
      used for a long-term therapy, it may be coadministered with other drugs. Present
      paper deals with the in vitro availability studies of metformin in presence of
      commonly used H(2) receptor antagonists. The later drugs compete with histamine
      for H(2) receptors and block gastric acid secretion and some cardiovascular
      effects of histamine. These studies were carried out in simulated gastric juices,
      simulating empty and full stomach, simulated intestinal juice and buffers of pH
      7.4 simulating blood pH at 37 degrees C on a B.P. 2003 dissolution test
      apparatus. Commonly prescribed H(2) receptor antagonists like cimetidine,
      ranitidine and famotidine were used in these studies. The present study clearly
      indicated that availability of metformin can be altered in presence of most of
      the H(2) receptor antagonists studied except in presence of famotidine at pH 4
      where the drug concentration remains unaltered. The availability of metformin was
      increased in simulated gastric juice, pH 7.4 and pH 9 (except ranitidine at pH 9)
      whereas the decrease in availability was observed in presence of cimetidine and
      ranitidine at pH 4 and ranitidine at pH 9. On the basis of these results, it is
      can be suggested that metformin should be coadministered with care along with
      H(2) receptor antagonists especially in case of ranitidine; although chances of
      adverse reactions are rare but decrease availability of metformin may result in
      delayed effect. On the other hand, increase in metformin concentration may result
      in hypoglycemic effects.

PMID- 16632450
TI  - Reactions of phthalimides with 1-methylethylamine: analgesic and anti
      inflammatory properties of resulting carboxamides.
AB  - The reaction of phthalimide derivatives (1a-c) with 1-methylethylamine in
      dimethylformamide (DMF) at room temperature afforded benzamido-N-prop-2-ynyl-2-(2
      methylethyl)-carboxamide (3a), benzamido-N-cyclopentyl-2-(2-methylethyl)-car
      boxamide (3b) and benzamido-N-benzyl-2-(2-methylethyl)-carboxamide (3c),
      respectively. In the carrageenan induced paw oedema test for anti-inflammatory
      activity, 3a (50 mg/kg) decreased the inflammatory response by 55% after 3 hrs
      while 3b and 3c exhibited significant reduction in the oedema level. The
      compounds 3a, 3b and 3c exhibited analgesic activities with 3b producing 76%
      inhibition. The activities were dose - dependent.

PMID- 16632451
TI  - A rp-HPLC method for the assay of cefpirome and its application in drug-metal
      interaction studies.
AB  - An accurate, sensitive and least time consuming RP-HPLC method for the estimation
      of cefpirome in the presence of essential and trace metal has been developed and
      validated. Cefpirome was eluted from a B144A, OD-5-100, C(18) (150 x 4.6 mm)
      column at room temperature with a mobile phase consisting of MeOH:H2O (15:85, %
      v/v) at a flow rate of 1 ml/minute, while UV detection was performed at 265 nm.
      The detection limit of cefpirome was 10 ng. Drug metal interaction studies were
      carried out at 37 degrees C to monitor the complexation of drug with metal ions.
      These studies were beneficial to determine the drug in therapeutic concentrations
      inside human body as well as its complexation with metal cations. The metals
      essential to human body like Mg(II), Ca(II), Cr(II), Mn(II), Fe (III), Co(II),
      Ni(II), Cu(II), Zn(II) & Cd(II) were in the form of chlorides. The carboxylic
      group of the dehydrothiazine ring has more binding capacity relative to other
      group that augments the drug complexes with essential and trace elements. The
      established HPLC method is rapid, accurate, and selective, because of its
      sensitivity and reproducibility. The order of complexation was
      ferric>chromium>copper>nickel>cadmium>zinc>magnesium>manganese>calcium>cobalt.

PMID- 16632452
TI  - Determination of the ascorbic acid content of two medicinal plants in Nigeria.
AB  - The fresh and dried leaves of two edible plants, Oldenlandia corymbosa and
      Dissotis rotundifolia have been assayed for their ascorbic acid content. They
      were found to be rich sources of ascorbic acid (vitamin C) when compared with
      some common garden fruits and vegetables. Students' t-test statistical analysis
      using INSTAT.EXE program for the results (mean+/-SEM) shows that there was no
      significant difference for the fresh leaves of the individual plants and also
      there is no significant difference for the dried leaves (P=0.05). However, there
      was significant difference between ascorbic acid content of the fresh and dried
      leaves of the same plant, obviously indicating that the fresh leaves contain more
      ascorbic acid than the dried leaves.

PMID- 16632453
TI  - The effects of mefenamic acid on hematocrit of the lizard, Uromastix hardwickii.
AB  - Mefenamic acid is an analgesic, antipyretic and anti-inflammatory agent. In
      addition induces several hematological disturbances. Present study was conducted
      to determine the alterations in blood PCV of the lizard Uromastix hardwickii
      after the administration of 7.1 mg/ml; 10.5 mg/ml and 14.0 mg/ml mefenamic acid
      per individual per day for 12 days to 3 test groups. The mean values of PCV were
      15.5+/-0.81%, 14.5+/-0.25% and 12.0+/-0.25% for 3 test groups respectively in
      comparison to 23.5+/-0.40% for control. Thus a significant dose dependant
      reduction in mean PCV per cent following the administration of mefenamic acid for
      12 days indicates the extra vascular hemolysis due to destructive change in the
      red cell membrane through autoantibody mechanism.

PMID- 16632454
TI  - Paediatric nosocomial infections: resistance pattern of clinical isolates.
AB  - Hospital acquired infections are transmitted to patients by hospital personnel
      and other patients, or they may arise from patient's own endogenous flora.
      Children are one of the most susceptible subjects associated in the hospital
      acquired infections and have a higher prevalence rate for infections. This
      problem is at its extremes in developing countries like Pakistan where in most of
      cases the severity depends on the hygienic conditions of the Hospitals and lack
      or lapse of infection control measures. To have a surveillance type of data in
      this regard, one hundred and twenty four isolates of Pseudomonas
      aeruginosa/Pseudomonas species, Staphylococcus aureus (MRSA/MSSA) and Klebsiella
      species, that are commonest among the nosocomial infection causing organisms,
      were collected from pediatric hospital settings in Karachi. A study of incidence
      and resistance pattern by Kirby Baur disc diffusion method, with selected
      antimicrobials, was carried out. These isolates were resistant against most
      antimicrobials tested. Drugs like mmipenem, meropenem, amikacin, vancomycin
      (especially in MRSA or BRSA), Fucidic acid (for burns and other infections) and
      some of the 3rd generation cephalosporins were found quite effective.

PMID- 16632455
TI  - Chemical composition of Egyptian and UAE propolis.
AB  - The chemical composition of propolis samples obtained from Behera, Egypt and
      Dubai, UAE, have been investigated by GC-MS and thirty four compounds have been
      tentatively identified. Some of these compounds have not been reported previously
      in Egyptian propolis from different regions. The Egyptian sample contains a high
      amount of aliphatic (13.7%) and aromatic (14.4%) acids. The alcohols, phenols and
      esters account for about 17.0% of the total content analysed. Some anthraquinone
      and flavone derivatives have also been detected (10%). The UAE sample is
      characterised by the presence of a high content of aliphatic acids (15.2%) and a
      low content of aromatic acids (4.3%). The aldehydes, alcohols, phenols and esters
      amount to about 9%. In addition to these some other compounds (high molecular
      weight alkanes, sugar derivatives, anthraquinone derivatives and flavone
      derivatives) are also present to the extent of about 33%.

PMID- 16632456
TI  - Obesity: an independent risk factor for systemic oxidative stress.
AB  - The role of obesity in diabetes mellitus, hyperlipidemia, colon cancer, sudden
      death and other cardiovascular diseases has confirmed in many recent research
      studies. In present study, it is hypothesized that obesity can serve as an
      independent risk factor for the decreased activities of cytoprotective
      antioxidants in humans and for the associated systemic oxidative stress. 150 age
      matched, female subjects with no history of smoking or biochemical evidence of
      diabetes mellitus, hypertension, hyperlipidemia, renal or liver disease or cancer
      were included in the study and were divided into different grades of obesity
      according to their body mass index (BMI). Hemoglobin and erythrocyte glutathione
      (GSH) concentrations were measured for each subject. The study suggests that
      increase BMI was found to be associated with a significant decrease in
      erythrocyte glutathione concentration. From these observations it is concluded
      that obesity even in the absence of smoking, diabetes mellitus, hyperlipidemia,
      renal or liver diseases can decrease the activities of body's protective
      antioxidants, and can enhance the systemic oxidative stress and should therefore
      receive the same attention as obesity with complications.

PMID- 16632457
TI  - Patient counseling by pharmacist - a focus on chronic illness.
AB  - The management of chronic illness needs lifestyle modifications and drug therapy
      for a long period. Patient understanding regarding the illness plays a very
      important role in management of chronic illness. Effective patient counseling
      makes the patient understand his/her illness, necessary lifestyle modifications
      and pharmacotherapy in a better way and thus enhance patient compliance. The
      pharmacist has immense responsibility in counseling the patients with chronic
      illness. The counseling pharmacist should possess adequate knowledge and should
      be an effective communicator, making use of the verbal and non-verbal
      communication skills.

PMID- 16632458
TI  - Fabrication of nanoparticles within polymeric pores for controlled release of
      drug.
AB  - Nanotechnology, a multidisciplinary scientific undertaking, involves creation and
      utilization of materials, devices or systems on the nanometer scale. The field
      has enabled the development of an amazing variety of methods for fabricating
      nanoparticles in recent years. The technology is expected to create innovations
      and play a critical role in the field of bio-pharmaceuticals especially in
      controlled release of drug delivery. Sol-gel technique is one of the most widely
      used techniques to fabricate porous nanoparticles within the polymer. Such
      nanoparticles have also applications in vascular drug delivery and release, site
      specific targeting (passive as well as active targeting), as well as transfusion
      medicine. This article concentrates mainly on fabrication of porous
      nanoparticles, its characterisation and its use for controlled release of drug.
      It also encompasses the strategies that have been used to translate and fabricate
      a wide range of particulate carriers e.g., nanospheres, liposomes, micelles, oil
      in-water emulsions, with prolonged circulation and/or target specificity. With
      regard to the targeting issues, attention is particularly focused on the
      importance of physiological barriers. we have also critically reviewed and
      assessed the fate and activity of biodegradable/bio-erodable polymeric drug
      delivery vehicles because the uniformity in degradation of these polymers is
      questionable.

PMID- 16632459
TI  - Long-term follow-up of a cohort of HIV-infected patients who discontinued
      maintenance therapy for cytomegalovirus retinitis.
AB  - PURPOSE: To determine the long-term safety of discontinuation of maintenance
      therapy for cytomegalovirus retinitis (CMVR) and to identify predictors for
      relapse. METHOD: This was a prospective cohort study. Patients with treated CMVR
      who responded to HAART were followed by ophthalmologic assessment, markers for
      CMV replication (blood and urine cultures, CMV antigenemia, CMV DNA by PCR), and
      in vitro lymphoproliferative responses to CMV and other antigens after
      discontinuation of CMVR maintenance therapy. RESULTS: 23 patients were followed a
      median of 34 (range, 5-61) months. Median CD4 count was 321/mm3 at enrollment and
      395/mm3 at last follow-up. HIV RNA was <50 copies/mL in 78% of patients at
      enrollment and 65% at last follow-up. One CMVR reactivation occurred at 12 months
      at a CD4 count of 395/mm3 (21%) and HIV RNA <50 copies/mL. Urine cultures were a
      poor predictive marker for reactivation. Other CMV replication markers had good
      negative predictive value. 96% of patients had a good lymphoproliferative
      response to CMV antigen in vitro. CONCLUSION: Maintenance therapy for CMVR can
      safely be discontinued in patients who have responded to HAART. Combining our
      results with the published literature, the risk of reactivation is estimated at
      0.016 per person year of follow-up. Markers to predict relapse and the need for
      re-initiation of maintenance therapy are not yet identified.

PMID- 16632460
TI  - Clinically stable treatment-experienced adults receiving tenofovir and
      didanosine.
AB  - METHOD: Analysis of virological, immunological, and clinical data over 24 weeks
      of treatment of drug-experienced patients administered didanosine (ddI) and
      tenofovir (TDF) plus either PI or NNRTI (17 patients) compared to 14 patients on
      ddI plus lamivudine and to 19 patients on ddI plus stavudine. RESULTS: Patients
      treated with TDF and ddI do not have a higher risk of early immunological or
      virological failure. CONCLUSION: Treatment success and increase in CD4+
      lymphocytes may depend, among other factors, on historical CD4+ nadir. These data
      agree with previous work and argue against preemptive switches for fear of side
      effects or immunological/virological failure away from a successful ddI-TDF
      combination in clinically stable drug-experienced patients.

PMID- 16632461
TI  - Atazanavir plasma concentrations vary significantly between patients and
      correlate with increased serum bilirubin concentrations.
AB  - BACKGROUND: Atazanavir (ATV) is recommended to be dosed at 400 mg once daily or
      300 mg daily coadministered with 100 mg ritonavir (RTV). METHOD: 31 male patients
      receiving ATV either alone or boosted with RTV for more than 2 weeks had ATV
      concentration measured by high performance liquid chromatography (HPLC). ATV
      concentrations were adjusted to obtain a 24-hour trough level using a standard
      pharmacokinetic formula. RESULTS: 25 samples were taken from patients who
      received 300 mg ATV, 6 with 200 mg, 3 with 400 mg, and 2 with 150 mg, all boosted
      with 100 mg RTV. In the unboosted group, patients received 400 mg (7) or 600 mg
      (2). The median adjusted 24-hour trough ATV concentration was 630 ng/mL
      (interquartile range [IQR] 355-1034) in the boosted and 113 ng/mL (IQR 50-225) in
      the unboosted group (p = .001). Median serum bilirubin concentration was 34 IU/L
      (IQR 27.5-49) and 41 IU/L (IQR 31-45) in the boosted and unboosted groups,
      respectively. In the boosted group, high ATV concentrations were significantly
      correlated with increased serum bilirubin concentrations (p = .003). CONCLUSION:
      ATV concentrations showed considerable interpatient variability. Bilirubin
      concentrations are an indicator of high ATV concentrations and may prove to be
      useful in selecting patients for therapeutic drug monitoring (TDM).

PMID- 16632462
TI  - A prospective trial comparing oocyte donor ovarian response and recipient
      pregnancy rates between suppression with gonadotrophin-releasing hormone agonist
      (GnRHa) alone and dual suppression with a contraceptive vaginal ring and GnRH.
AB  - BACKGROUND: Contraceptive treatment before gonadotrophin-releasing hormone
      agonist administration presents advantages in women with a tendency to hyper
      response and simplifies donor-recipient treatment synchronization. This study
      compares response to gonadotrophin stimulation under hypophyseal suppression in
      oocyte donors with or without vaginal contraceptive pretreatment. METHODS: One
      hundred and ninety oocyte donors were recruited in a single centre and
      prospectively assigned to one of two treatment groups, according to the day of
      the week menstruation initiated: Group VC-, no prior vaginal contraceptive and
      Group VC+, prior vaginal contraceptive. RESULTS: VC+ patients presented a
      significantly higher cancellation rate, lower plasma estradiol levels and fewer
      follicles >12 mm on the day of hCG, versus the VC- group. Number of oocytes
      recovered was significantly lower in the VC+ group. All the cases of severe
      ovarian hyperstimulation syndrome (SOHSS) were in the VC- group. Pregnancy rates
      by embryo transfer to synchronic recipients were similar between VC+ and VC-
      (59.5 versus 57.9%, respectively). CONCLUSIONS: Vaginal contraceptive
      pretreatment resulted in a higher ovarian suppression, whereas SOHSS rate was
      lower than in donors who did not receive pretreatment. There were no differences
      in pregnancy rates between the two groups of synchronic oocyte recipients.

PMID- 16632463
TI  - Expression of melatoninergic receptors in human placental choriocarcinoma cell
      lines.
AB  - BACKGROUND: Melatonin crosses the placenta and enters the fetal circulation.
      Moreover, experimental data suggest a possible influence of melatonin on
      placental function and fetal development in humans. To date, the expression and
      role of melatonin receptors in human placenta choriocarcinoma cell lines and in
      human term placental tissues remain to be elucidated. METHODS AND RESULTS:
      Results from RT-PCR, western blotting and confocal microscopy demonstrated that
      the MT1, MT2 and RORalpha1 melatonin receptors are expressed in the human term
      placental tissues and in choriocarcinoma cell lines JEG-3 and BeWo. Furthermore,
      enzyme-linked immunosorbent assay showed that 6-chloromelatonin (a melatonin
      agonist) inhibits, in a dose-dependent manner, forskolin-stimulated hCG-beta
      secretion in JEG-3 (P < 0.001) and BeWo (P < 0.05) cells but had no effect on
      basal human chorionic gonadotrophin (hCG-beta) levels. This effect of 6
      chloromelatonin on forskolin-stimulated HCG-beta secretion was abolished by
      pertussis toxin (PTX), suggesting that melatonin regulates hCG-beta production by
      an action involving an inhibitory Gi/o protein. In PTX-treated BeWo cells, 6
      chloromelatonin stimulated basal hCG-beta secretion (P < 0.001). CONCLUSION:
      These results demonstrate, for the first time, the expression of melatonin
      receptors in human term placental tissues and in choriocarcinoma cells and
      suggest a possible paracrine/autocrine function for melatonin in human placenta.

PMID- 16632464
TI  - Protamine 2 precursors, protamine 1/protamine 2 ratio, DNA integrity and other
      sperm parameters in infertile patients.
AB  - BACKGROUND: The protamine 1-to-protamine 2 ratio (P1/P2) is altered in the sperm
      cells of some infertile patients. Also, evidence for increased protamine 2
      precursors (pre-P2) in a few patients has been reported. But so far, there have
      been no studies measuring simultaneously these two variables in a large number of
      patients. METHODS: We measured the P1/P2 ratio and the presence of pre-P2 using,
      for the first time, an antibody specific to the precursor pre-P2, together with
      other sperm parameters in 224 infertile patients. Additionally, the DNA integrity
      was assessed by terminal transferase dUTP nick-end labelling (TUNEL) in a subset
      of the samples. RESULTS: Pre-P2 levels show a significant positive correlation
      with the P1/P2 ratio, with the presence of other proteins and, at low pre-P2
      levels, with TUNEL-positive sperm. An inverse correlation with sperm count,
      normal morphology and motility was detected. CONCLUSIONS: The levels of pre-P2
      may provide clues into the pathogenic mechanisms of infertility. The increased
      proportion of pre-P2 in some patients with increased P1/P2 ratio suggests an
      involvement of pre-P2 processing. The positive correlation between TUNEL-positive
      sperm and pre-P2 at low pre-P2/P2 ratios also suggests a link between deficient
      protamine processing and decreased DNA integrity.

PMID- 16632465
TI  - Regulation of cGMP-dependent protein kinase expression by Rho and Kruppel-like
      transcription factor-4.
AB  - Type I cGMP-dependent protein kinase (PKG I) plays a major role in vascular
      homeostasis by mediating smooth muscle relaxation in response to nitric oxide,
      but little is known about the regulation of PKG I expression in smooth muscle
      cells. We found opposing effects of RhoA and Rac1 on cellular PKG I expression:
      (i) cell density-dependent changes in PKG I expression varied directly with Rac1
      activity and inversely with RhoA activity; (ii) RhoA activation by calpeptin
      suppressed PKG I, whereas RhoA down-regulation by small interfering RNA increased
      PKG I expression; and (iii) PKG I promoter activity was suppressed in cells
      expressing active RhoA or Rho-kinase but was enhanced in cells expressing active
      Rac1 or a dominant negative RhoA. Sp1 consensus sequences in the PKG I promoter
      were required for Rho regulation and bound nuclear proteins in a cell density
      dependent manner, including the Kruppel-like factor 4 (KLF4). KLF4 was identified
      as a major trans-acting factor at two proximal Sp1 sites; active RhoA suppressed
      KLF4 DNA binding and trans-activation potential on the PKG I promoter.
      Experiments with actin-binding agents suggested that RhoA could regulate KLF4 via
      its ability to induce actin polymerization. Regulation of PKG I expression by
      RhoA may explain decreased PKG I levels in vascular smooth muscle cells found in
      some models of hypertension and vascular injury.

PMID- 16632466
TI  - Mutations Phe785Leu and Thr618Met in Na+,K+-ATPase, associated with familial
      rapid-onset dystonia parkinsonism, interfere with Na+ interaction by distinct
      mechanisms.
AB  - The Na(+),K(+)-ATPase plays key roles in brain function. Recently, missense
      mutations in the Na(+),K(+)-ATPase were found associated with familial rapid
      onset dystonia parkinsonism (FRDP). Here, we have characterized the functional
      consequences of FRDP mutations Phe785Leu and Thr618Met. Both mutations lead to
      functionally altered, but active, Na(+),K(+)-pumps, that display reduced apparent
      affinity for cytoplasmic Na(+), but the underlying mechanism differs between the
      mutants. In Phe785Leu, the interaction of the E(1) form with Na(+) is defective,
      and the E(1)-E(2) equilibrium is not displaced. In Thr618Met, the Na(+) affinity
      is reduced because of displacement of the conformational equilibrium in favor of
      the K(+)-occluded E(2)(K(2)) form. In both mutants, K(+) interaction at the
      external activating sites of the E(2)P phosphoenzyme is normal. The change of
      cellular Na(+) homeostasis is likely a major factor contributing to the
      development of FRDP in patients carrying the Phe785Leu or Thr618Met mutation.
      Phe785Leu moreover interferes with Na(+) interaction on the extracellular side
      and reduces the affinity for ouabain significantly. Analysis of two additional
      Phe(785) mutants, Phe785Leu/Leu786Phe and Phe785Tyr, demonstrated that the
      aromatic function of the side chain, as well as its exact position, is critical
      for Na(+) and ouabain binding. The effects of substituting Phe(785) could be
      explained by structural modeling, demonstrating that Phe(785) participates in a
      hydrophobic network between three transmembrane segments. Thr(618) is located in
      the cytoplasmic part of the molecule near the catalytic site, and the structural
      modeling indicates that the Thr618Met mutation interferes with the bonding
      pattern in the catalytic site in the E(1) form, thereby destabilizing E(1)
      relative to E(2)(K(2)).

PMID- 16632467
TI  - The multi-KH domain protein of Saccharomyces cerevisiae Scp160p contributes to
      the regulation of telomeric silencing.
AB  - Multi-KH domain proteins are highly evolutionarily conserved proteins that
      associate to polyribosomes and participate in RNA metabolism. Recent evidence
      indicates that multi-KH domain proteins also contribute to the structural
      organization of heterochromatin both in mammals and Drosophila. Here, we show
      that the multi-KH domain protein of Saccharomyces cerevisiae, Scp160p,
      contributes to silencing at telomeres and at the mating-type locus, but not to
      ribosomal silencing. The contribution of Scp160p to silencing is independent of
      its binding to the ribosome as deletion of the last two KH domains, which mediate
      ribosomal binding, has no effect on silencing. Disruption of SCP160 increases
      cell ploidy but this effect is also independent of the contribution of Scp160p to
      telomeric silencing as strong relief of silencing is observed in Deltascp160
      cells with normal ploidy and, vice versa, Deltascp160 cells with highly increased
      ploidy show no significant silencing defects. The TPE phenotype of Deltascp160
      cells associates to a decreased Sir3p deposition at telomeres and, in good
      agreement, silencing is rescued by SIR3 overexpression and in a
      Deltarif1Deltarif2 mutant. Scp160p shows a distinct perinuclear localization that
      is independent of its ability to bind ribosomes. Moreover, telomere clustering at
      the nuclear envelope is perturbed in Deltascp160 cells and disruption of the
      histone deacetylase RPD3, which is known to improve telomere clustering, rescues
      telomeric silencing in Deltascp160 cells. These results are discussed in the
      context of a model in which Scp160p contributes to silencing by helping telomere
      clustering.

PMID- 16632468
TI  - The AddAB helicase/nuclease forms a stable complex with its cognate chi sequence
      during translocation.
AB  - The Bacillus subtilis AddAB enzyme possesses ATP-dependent helicase and nuclease
      activities, which result in the unwinding and degradation of double-stranded DNA
      (dsDNA) upon translocation. Similar to its functional counterpart, the
      Escherichia coli RecBCD enzyme, it also recognizes and responds to a specific DNA
      sequence, referred to as Chi (chi). Recognition of chi triggers attenuation of
      the 3'- to 5'-nuclease, which permits the generation of recombinogenic 3'
      overhanging, single-stranded DNA (ssDNA), terminating at chi. Although the RecBCD
      enzyme briefly pauses at chi, no specific binding of RecBCD to chi during
      translocation has been documented. Here, we show that the AddAB enzyme
      transiently binds to its cognate chi sequence (chi(Bs): 5'-AGCGG-3') during
      translocation. The binding of AddAB enzyme to the 3'-end of the chi(Bs)-specific
      ssDNA results in protection from degradation by exonuclease I. This protection is
      gradually reduced with time and lost upon phenol extraction, showing that the
      binding is non-covalent. Addition of AddAB enzyme to processed, chi(Bs)-specific
      ssDNA that had been stripped of all protein does not restore nuclease protection,
      indicating that AddAB enzyme binds to chi(Bs) with high affinity only during
      translocation. Finally, protection of chi(Bs)-specific ssDNA is still observed
      when translocation occurs in the presence of competitor chi(Bs)-carrying ssDNA,
      showing that binding occurs in cis. We suggest that this transient binding of
      AddAB to chi(Bs) is an integral part of the AddAB-chi(Bs) interaction and propose
      that this molecular event underlies a general mechanism for regulating the
      biochemical activities and biological functions of RecBCD-like enzymes.

PMID- 16632469
TI  - CAAT/enhancer-binding protein delta and cAMP-response element-binding protein
      mediate inducible expression of the nerve growth factor gene in the central
      nervous system.
AB  - Nerve growth factor (NGF) synthesis in the rat cerebral cortex is induced by the
      beta2-adrenergic receptor agonist clenbuterol (CLE). Because NGF is a crucial
      neurotrophic factor for basal forebrain cholinergic neurons, defining the
      mechanisms that regulate its transcription is important for developing
      therapeutic strategies to treat pathologies of these neurons. We previously
      showed that the transcription factor CCAAT/enhancer-binding protein delta
      (C/EBPdelta) contributes to NGF gene regulation. Here we have further defined the
      function of C/EBPdelta and identified a role for cAMP response element-binding
      protein (CREB) in NGF transcription. Inhibition of protein kinase A in C6-2B
      glioma cells suppressed CLE induction of an NGF promoter-reporter construct,
      whereas overexpression of protein kinase A increased NGF promoter activity,
      particularly in combination with C/EBPdelta. A CRE-like site that binds CREB was
      identified in the proximal NGF promoter, and C/EBPdelta and CREB were found to
      associate with the NGF promoter in vivo. Deletion of the CRE and/or C/EBP sites
      reduced CLE responsiveness of the promoter. In addition, ectopic expression of
      C/EBPdelta in combination with CLE treatment increased endogenous NGF mRNA levels
      in C6-2B cells. C/EBPdelta null mice showed complete loss of NGF induction in the
      cerebral cortex following CLE treatment, demonstrating a critical role for
      C/EBPdelta in regulating beta2-adrenergic receptor-mediated NGF expression in
      vivo. Thus, our findings demonstrate a critical role for C/EBPdelta in regional
      expression of NGF in the brain and implicate CREB in CLE-induced NGF gene
      transcription.

PMID- 16632470
TI  - Activated Jak2 with the V617F point mutation promotes G1/S phase transition.
AB  - Hematopoietic stem cells in myeloproliferative diseases mostly retain the
      potential to differentiate but are characterized by hyper-responsiveness to
      growth factors, as well as partial factor-independent growth. The V617F
      activating point mutation in Jak2 has recently been associated with
      myeloproliferative disorders. Using various cell line models, mechanisms that
      contribute to Jak2V617-mediated signaling were investigated. Treatment of the
      Jak2V617F mutant-expressing erythroid leukemia cell line HEL with a small
      molecule Jak2 inhibitor was associated with a dose-dependent G(1) cell cycle
      arrest. This inhibition correlated with decreased expression of cyclin D2 and
      increased expression of the cell cycle inhibitor p27(Kip). Inhibition of
      Jak2V617F with a Jak2-targeted small interfering RNA approach resulted in a
      similar phenotype. Mechanisms leading to altered p27(Kip) and cyclin D2 likely
      involve inhibition of STAT5, a major target of Jak2 in hematopoietic cells,
      because a constitutively active form of STAT5 reduced p27(Kip) and increased
      cyclin D2 expression. Jak2V617F and constitutively active STAT5 also induced high
      levels of reactive oxygen species, which are sufficient to promote G(1)/S phase
      transition. In contrast, treatment of HEL cells with the antioxidant N
      acetylcysteine decreased cell growth or expression of cyclin D2 and increased
      expression of p27(Kip). Similar results were obtained in BaF3 cells transfected
      with Jak2V617F, but these cells required coexpression of the erythropoietin
      receptor for optimal signaling. These results suggest that regulation of cyclin
      D2 and p27(Kip) in combination with redox-dependent processes promotes G(1)/S
      phase transition downstream of Jak2V617F/STAT5 and therefore hint at potential
      novel targets for drug development that may aid traditional therapy.

PMID- 16632471
TI  - Complete structures of Bordetella bronchiseptica and Bordetella parapertussis
      lipopolysaccharides.
AB  - The structures of the lipopolysaccharide (LPS) core and O antigen of Bordetella
      bronchiseptica and Bordetella parapertussis are known, but how these two regions
      are linked to each other had not been determined. We have studied LPS from
      several strains of these microorganisms to determine the complete carbohydrate
      structure of the LPS. LPS was analyzed using different chemical degradations, NMR
      spectroscopy, and mass spectrometry. This identified a novel pentasaccharide
      fragment that links the O chain to the core in all the LPS studied. In addition,
      although the O chain of these bacteria was reported as a homopolymer of 1,4
      linked 2,3-diacetamido-2,3-dideoxy-alpha-galacturonic acid, we discovered that
      the polymer contains several amidated uronic acids, the number of which varies
      between strains. These new data describe the complete structure of the LPS
      carbohydrate backbone for both Bordetella species and help to explain the complex
      genetics of LPS biosynthesis in these bacteria.

PMID- 16632472
TI  - Structural, biochemical, and dynamic characterizations of the hRPB8 subunit of
      human RNA polymerases.
AB  - The RPB8 subunit is present in all three types of eukaryotic RNA polymerases and
      is highly conserved during evolution. It is an essential subunit required for the
      transcription of nuclear genes, but the detailed mechanism including its
      interactions with different subunits and oligonucleotides remains largely
      unclear. Herein, we report the three-dimensional structure of human RPB8 (hRPB8)
      at high resolution determined by NMR spectroscopy. The protein fold comprises an
      eight-stranded beta-barrel, six short helices, and a large unstructured Omega
      loop. The overall structure of hRPB8 is similar to that of yRPB8 from
      Saccharomyces cerevisiae and belongs to the oligonucleotide/oligosaccharide
      binding fold. However, several features of the tertiary structures are notably
      different between the two proteins. In particular, hRPB8 has a more clustered
      positively charged binding interface with the largest subunit RPB1 of the RNA
      polymerases. We employed biochemical methods to detect its interactions with
      different single-stranded DNA sequences. In addition, single-stranded DNA
      titration experiments were performed to identify the residues involved in
      nonspecific binding with different DNA sequences. Furthermore, we characterized
      the millisecond time scale conformational flexibility of hRPB8 upon its binding
      to single-stranded DNA. The current results demonstrate that hRPB8 interacts with
      single-stranded DNA nonspecifically and adopts significant conformational
      changes, and the hRPB8/single-stranded DNA complex is a fast exchanging system.
      The solution structure in conjunction with the biochemical and dynamic studies
      reveal new aspects of this subunit in the molecular assembly and the biological
      function of the human nuclear RNA polymerases.

PMID- 16632473
TI  - Dissecting the biological functions of Drosophila histone deacetylases by RNA
      interference and transcriptional profiling.
AB  - Zinc-dependent histone deacetylases (HDACs) are a family of hydrolases first
      identified as components of transcriptional repressor complexes, where they act
      by deacetylating lysine residues at the N-terminal extensions of core histones,
      thereby affecting transcription. To get more insight into the biological
      functions of the individual HDAC family members, we have used RNA interference in
      combination with microarray analysis in Drosophila S2 cells. Silencing of
      Drosophila HDAC1 (DHDAC1), but not of the other DHDAC family members, leads to
      increased histone acetylation. Silencing of either DHDAC1 or DHDAC3 leads to cell
      growth inhibition and deregulated transcription of both common and distinct
      groups of genes. Silencing DHDAC2 leads to increased tubulin acetylation levels
      but was not associated with a deregulation of gene expression. No growth of
      phenotype and no significant deregulation of gene expression was observed upon
      silencing of DHDAC4 and DHDACX. Loss of DHDAC1 or exposure of S2 cells to the
      small molecule HDAC inhibitor trichostatin both lead to a G(2) arrest and were
      associated with significantly overlapping gene expression signatures in which
      genes involved in nucleobase and lipid metabolism, DNA replication, cell cycle
      regulation, and signal transduction were over-represented. A large number of
      these genes were shown to also be deregulated upon loss of the co-repressor SIN3
      (Pile, L. A., Spellman, P. T., Katzenberger, R. J., and Wassarman, D. A. (2003)
      J. Biol. Chem. 278, 37840-37848). We conclude the following. 1) DHDAC1 and -3
      have distinct functions in the control of gene expression. 2) Under the tested
      conditions, DHDAC2, -4, and X have no detectable transcriptional functions in S2
      cells. 3) The anti-proliferative and transcriptional effects of trichostatin are
      largely recapitulated by the loss of DHDAC1. 4) The deacetylase activity of
      DHDAC1 significantly contributes to the repressor function of SIN3.

PMID- 16632474
TI  - Ubiquitous calpains promote both apoptosis and survival signals in response to
      different cell death stimuli.
AB  - The mu- and m-calpain proteases have been implicated in both pro- or anti
      apoptotic functions. Here we compared cell death responses and apoptotic or
      survival signaling pathways in primary mouse embryonic fibroblasts (MEFs) derived
      from wild type or capn4 knock-out mice which lack both mu- and m-calpain
      activities. Capn4(-/-) MEFs displayed resistance to puromycin, camptothecin,
      etoposide, hydrogen peroxide, ultraviolet light, and serum starvation, which was
      consistent with pro-apoptotic roles for calpain. In contrast, capn4(-/-) MEFs
      were more susceptible to staurosporine (STS) and tumor necrosis factor alpha
      induced cell death, which provided evidence for anti-apoptotic signaling roles
      for calpain. Bax activation, release of cytochrome c, and activation of caspase-9
      and caspase-3 all correlated with the observed cell death responses of wild type
      or capn4(-/-) MEFs to the various challenges, suggesting that calpain might play
      distinct roles in transducing different death signals to the mitochondria. There
      was no evidence that calpain cleaved Bcl-2 family member proteins that regulate
      mitochondrial membrane permeability including Bcl-2, Bcl-xl, Bad, Bak, Bid, or
      Bim. However, activation of the phosphatidylinositol 3 (PI3)-kinase/Akt survival
      signaling pathway was compromised in capn4(-/-) MEFs under all challenges
      regardless of the cell death outcome, and blocking Akt activation using the PI3
      kinase inhibitor LY294002 abolished the protective effect of calpain to STS
      challenge. We conclude that the anti-apoptotic function of calpain in tumor
      necrosis factor alpha- and STS-challenged cells relates to a novel role in
      activating the PI3-kinase/Akt survival pathway.

PMID- 16632475
TI  - Urokinase signaling through its receptor protects against anoikis by increasing
      BCL-xL expression levels.
AB  - The acquired capabilities of resistance to apoptotic cell death and tissue
      invasion are considered to be obligate steps in tumor progression. The binding of
      the serine protease urokinase (uPA) to its receptor (uPAR) plays a central role
      in the molecular events coordinating tumor cell adhesion, migration, and
      invasion. Here we investigate whether uPAR signaling may also prevent apoptosis
      following loss of anchorage (anoikis) or DNA damage. If nontransformed human
      retinal pigment epithelial cells are pre-exposed to uPA or to its noncatalytic
      amino-terminal region (residues 1-135), they exhibit a markedly reduced
      susceptibility to anoikis as well as to UV-induced apoptosis. This anti-apoptotic
      effect is retained by a uPA-derived synthetic peptide corresponding to the
      receptor binding domain and is inhibited by anti-uPAR polyclonal antibodies.
      Furthermore, the stable reduction of uPA or uPAR expression by RNA interference
      leads to an increased susceptibility to UV-, cisplatin-, and detachment-induced
      apoptosis. In particular, the level of uPAR expression positively correlates with
      cell resistance to anoikis. The protective ability of uPA is prevented by UO126,
      LY294002, by an MAPK targeting small interference RNA, and by a dominant negative
      Akt variant. Accordingly, incubation of retinal pigment epithelial cells with uPA
      elicits a time-dependent enhancement of MAPK and phosphatidylinositol 3-kinase
      activities as well as the transcriptional activation of Bcl-xL anti-apoptotic
      factor. Vice versa, the silencing of Bcl-xL expression prevents uPA protection
      from anoikis. In conclusion, the data show that ligand engagement of uPAR
      promotes cell survival by activating Bcl-xL transcription through the MEK/ERK-
      and phosphatidylinositol 3-kinase/Akt-dependent pathways.

PMID- 16632476
TI  - Increased colon tumor susceptibility in azoxymethane treated CEABAC transgenic
      mice.
AB  - Human carcinoembryonic antigen (CEA), a widely used clinical tumor marker, and
      its close relative, CEACAM6, are often overexpressed in many cancers. This
      correlation suggests a possible instrumental role in tumorigenesis, which is
      supported by extensive results obtained with several in vitro systems. The
      implication that these results could also apply in vivo warrants investigation.
      Since mice do not possess homologs of the glycophosphatidyl inositol (GPI)
      anchored CEACAM family genes CEA, CEACAM6 and CEACAM7, we have constructed
      transgenic mice harboring a 187 kb portion of the human CEACAM family gene locus
      contained in a bacterial artificial chromosome (CEABAC) that includes genes
      coding for CEA, CEACAM6 and CEACAM7. In this study, we treated the CEABAC mice
      and their wild-type littermates with azoxymethane (AOM) in order to induce colon
      tumor formation. At 20 weeks post-treatment, the CEABAC transgenics showed more
      than a 2-fold increase in mean tumor load relative to their wild-type
      littermates. Cell surface expression of CEA and CEACAM6 increased by 2- and 20
      fold, respectively, in colonocytes from the tumors relative to colonocytes from
      non-AOM treated transgenics and a de-regulated spatial pattern of CEA/CEACAM6
      expression was found in 'normal' crypts adjacent to the tumors, thus mimicking
      closely the situation in human colon tumorigenesis. A modestly increased
      incidence of beta-catenin mutations also observed in the AOM-induced CEABAC
      tumors. These results show that expression of the human GPI-anchored CEACAM
      family genes predisposes mice to acquire and/or retain essential mutations
      necessary for sporadic colon tumor development.

PMID- 16632477
TI  - Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12
      dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek
      pouch, and inhibition of carcinogenesis by its inhibitors.
AB  - Previous studies have shown that aberrant arachidonic acid (AA) metabolism,
      especially cyclooxygenase-2 (Cox-2) and 5-lipoxygenase (5-Lox) pathways, are
      activated during oral carcinogenesis, and can be targeted for cancer prevention.
      This study was designed to investigate the importance of 5-Lox/leukotriene A4
      hydrolase (LTA4H) pathway of AA metabolism in 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced hamster cheek pouch carcinogenesis. In a short-term study, topical
      application of DMBA for 3 weeks induced severe inflammation and aberrant AA
      metabolism. Subsequent topical treatment with zileuton, celecoxib, or their
      combination for 1 week significantly suppressed aberrant AA metabolism and cell
      proliferation in the oral epithelium. Interestingly, zileuton was effective in
      inhibiting biosynthesis of multiple AA metabolites, including leukotriene B4
      (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid and prostaglandin E2 (PGE2),
      while celecoxib only suppressed PGE2 biosynthesis significantly at a high dose.
      In a long-term carcinogenesis study topical application of LTB4 or PGE2 enhanced
      oral carcinogenesis by increasing the incidence and volume of visible tumors, and
      the incidence of squamous cell carcinoma (SCC). To further examine the role of
      LTB4 in oral carcinogenesis, two LTA4H inhibitors, bestatin and SA6541, were
      evaluated in a long-term chemoprevention experiment. Both agents significantly
      inhibited SCC, and such an inhibition correlated with reduced levels of LTB4 in
      hamster cheek pouch. In summary, our studies have demonstrated that 5-Lox/LTA4H
      pathway is one of the major AA-metabolizing pathways involved in DMBA-induced
      oral carcinogenesis in hamsters, and may be targeted for chemoprevention.

PMID- 16632478
TI  - Patients' views on the quality of health care for rheumatoid arthritis.
AB  - OBJECTIVE: To study the experiences and views of patients with rheumatoid
      arthritis (RA) on the quality of health care received in primary and secondary
      care. METHOD: Semi-structured interviews with 26 individual patients with RA;
      these were stratified by sex, ethnicity and disease duration, based on the
      treated prevalence cohort of patients attending two outpatient clinics in South
      East England. RESULTS: Patients highlighted four main factors which influenced
      their attitude and approach towards hospital staff and the treatment offered: (i)
      their past experiences with the National Health Service (NHS), (ii) their own
      health beliefs, (iii) professional attitudes (e.g. listening to patients,
      receiving feedback on disease processes) and (iv) organizational aspects (e.g.
      good communication between health professionals) which would make their visits to
      the outpatient clinic easier. CONCLUSION: Most patients no longer see themselves
      as passive recipients of care. They appreciate acknowledgement from health care
      professionals of their contribution towards management of their own chronic
      illness, and welcome a more equal dialogue with health care staff. This is
      consistent with the emphasis of the Department of Health document on 'Supporting
      People with Long-term Conditions' such as RA.

PMID- 16632479
TI  - Need for and receipt of hip and knee replacement--a national population survey.
AB  - OBJECTIVES: Hip and knee joint replacements are effective, and yet little is
      known about how closely the need for joint replacement matches supply in
      different population groups. Our objective was to compare the prevalence of
      existing joint replacements with that of need in population groups in England.
      METHODS: A total of 7101 people aged 60 yrs or older, representative of the
      population of England, were interviewed. Participants were asked about both
      receipt and need for joint replacement, socio-economic status and co-morbidity.
      'Need' classification was based on hip or knee pain and difficulty walking, with
      adjustment for potential surgical contraindications. Associations between
      participants' characteristics and both need and receipt were estimated. RESULTS:
      The prevalence of existing joint replacement (receipt) was 6% [95% confidence
      intervals (CI) 5, 6], and this was lower in the North than the South [adjusted
      odds ratio (OR) 0.72, CI 0.53, 0.96]. In contrast, the prevalence of estimated
      need was higher in the North (OR 1.27, CI 1.03, 1.58). Need was greater in women
      than men (OR 1.30, CI 1.09, 1.53), and showed an increasing gradient from the
      wealthiest to poorest quintile (ORs 1.00, 1.52, 2.18, 2.49, 3.23). In contrast,
      receipt did not differ significantly by sex or socio-economic group. CONCLUSIONS:
      People living in the North of England, women and the less wealthy experience
      relatively high levels of need, yet do not receive relatively more hip and knee
      joint replacements.

PMID- 16632480
TI  - Obesity and cardiovascular risk factors in rheumatoid arthritis.

PMID- 16632481
TI  - Inhibitory characteristics of citrullinated telopeptides of type I and II
      collagens for autoantibody binding in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II
      collagens inhibit the binding of autoantibodies to the respective antigens
      immobilized onto solid phase, and to use modifications of previous methods to re
      analyse rheumatoid arthritis (RA) and control serum samples. METHODS:
      Autoantibody binding was inhibited with normal or citrullinated
      carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods.
      Serum samples were available from 120 patients with RA and 81 controls. RESULTS:
      Autoantibodies that bind normal C-telopeptides were not inhibited with soluble
      normal or citrullinated telopeptides. However, the antibodies that bind only
      citrullinated telopeptides could be inhibited with corresponding citrullinated
      telopeptides. Thus, it is not necessary to study the binding of autoantibodies to
      normal collagens if the specificity of their binding is assessed by immunological
      inhibition. For type I telopeptide, there are two arginines, the latter of which,
      when citrullinated, is important for binding. For type II telopeptide, there is
      one arginine, which is important when citrullinated. The other amino acids, e.g.
      the last alanine, have only a slight effect on binding. These improved methods
      differentiate better between RA patients, who have specific citrullinated
      autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on
      inhibition assay, it is possible to measure the autoantibodies binding
      specifically to citrullinated telopeptides of type I and II collagens. When only
      one assay is involved, variance is decreased and the overall performance is
      easier than before.

PMID- 16632482
TI  - Long-term observation of patients with anti-neutrophil cytoplasmic antibody
      associated vasculitis treated with rituximab.
AB  - OBJECTIVE: Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to
      be quite effective in the treatment of immune disorders resulting from
      autoantibodies. We prospectively studied the long-term effects of rituximab in 10
      patients with anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis
      refractory to conventional therapy (n=3) or in second or subsequent relapse
      (n=7). METHODS: The median age of patients was 53 yrs (range 38-70 yrs). Eight
      were classified as Wegener's granulomatosis, and two as microscopic polyangiitis.
      Clinical activity was assessed using the Birmingham Vasculitis Activity Score
      modification for Wegener's granulomatosis. Treatment consisted of intravenous
      infusions of rituximab given at the dose of 375 mg/m2 weekly for four consecutive
      weeks. RESULTS: All patients experienced a rapid clinical improvement following
      the administration of rituximab, with nine complete responses and one partial
      response at 6 months. With a median follow-up of 33.5 months (range 26-45
      months), three patients have thus far relapsed. Retreatment with the monoclonal
      antibody at the same dose and schedule resulted in a new sustained response in
      all these patients. Rituximab therapy resulted in prolonged B-cell depletion. The
      ANCA titres decreased significantly in all patients, with eight out of 10
      becoming ANCA-negative and three remaining ANCA-negative even after B-cell
      recovery. Infusion-related side effects were observed in one patient, but were of
      mild intensity and did not require discontinuation of treatment. CONCLUSIONS:
      Rituximab is an effective and well-tolerated treatment for patients with ANCA
      associated vasculitis and should be strongly considered in severely affected
      patients who do not respond to standard therapy or in those in whom cytotoxic
      therapy bears a high risk of morbidity.

PMID- 16632483
TI  - Effectiveness of interventions for the treatment of acute and prevention of
      recurrent gout--a systematic review.
AB  - OBJECTIVE: To determine the evidence for the effectiveness of treatments for
      acute gout and the prevention of recurrent gout. METHOD: Seven electronic
      databases were searched for randomized controlled trials of treatments for gout
      from their inception to the end of 2004. No language restrictions were applied.
      All randomized controlled trials of treatments routinely available for the
      treatment of gout were included. Trials of the prevention of recurrence were
      included only if patients who had had gout and had at least 6 months of follow-up
      were studied. RESULTS: We found 13 randomized controlled trials of treatment for
      acute gout, two of which were placebo controlled. Colchicine was found to be
      effective in one study; however, the entire colchicine group developed toxicity.
      The only robust conclusion from studies of non-steroidal anti-inflammatory drugs
      is that pain relief from indometacin and etoricoxib are equivalent. We found one
      randomized controlled trial, reported only as a conference abstract, of recurrent
      gout prevention. CONCLUSION: The shortage of robust data to inform the management
      of a common problem such as gout is surprising. All of the drugs used to treat
      gout can have serious side effects. The incidence of gout is highest in the
      elderly population. It is in this group, who are at a high risk of serious
      adverse events, that we are using drugs of known toxicity. The balance of risks
      and benefits for the drug treatment of gout needs to be reassessed.

PMID- 16632484
TI  - In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs
      its interaction with RPGR and results in early-onset retinal degeneration in the
      rd16 mouse.
AB  - Centrosome- and cilia-associated proteins play crucial roles in establishing
      polarity and regulating intracellular transport in post-mitotic cells. Using
      genetic mapping and positional candidate strategy, we have identified an in-frame
      deletion in a novel centrosomal protein CEP290 (also called NPHP6), leading to
      early-onset retinal degeneration in a newly identified mouse mutant, rd16. We
      demonstrate that CEP290 localizes primarily to centrosomes of dividing cells and
      to the connecting cilium of retinal photoreceptors. We show that, in the retina,
      CEP290 associates with several microtubule-based transport proteins including
      RPGR, which is mutated in approximately 15% of patients with retinitis
      pigmentosa. A truncated CEP290 protein (DeltaCEP290) is detected in the rd16
      retina, but in considerably reduced amounts; however, the mutant protein exhibits
      stronger association with specific RPGR isoform(s). Immunogold labeling studies
      demonstrate the redistribution of RPGR and of phototransduction proteins in the
      photoreceptors of rd16 retina. Our findings suggest a critical function for
      CEP290 in ciliary transport and provide insights into the mechanism of early
      onset photoreceptor degeneration.

PMID- 16632485
TI  - The molecular basis for tissue specificity of the oxidative phosphorylation
      deficiencies in patients with mutations in the mitochondrial translation factor
      EFG1.
AB  - Defects in mitochondrial translation are associated with a remarkable, but
      unexplained diversity of clinical phenotypes. Here we have investigated the
      molecular basis for tissue specificity in patients with a fatal hepatopathy due
      to mutations in the mitochondrial translation elongation factor EFG1. Blue-native
      gel electrophoresis revealed unique, tissue-specific patterns in the nature and
      severity of the defect. Liver was the most severely affected tissue, with less
      than 10% residual assembly of complexes I and IV, and a 50% decrease in complex
      V. Skeletal muscle showed a 50% reduction in complex I, and complexes IV and V
      were 20% of control. In fibroblasts, complexes I and IV were 20% of control, and
      there was a 40-60% reduction in complexes III and V. In contrast, except for a
      50% decrease in complex IV, all complexes were near normal in heart. The severity
      of the defect paralleled the steady-state level of the mutant EFG1 protein, which
      varied from 60% of control in heart to undetectable in liver. The ratio of
      translation elongation factors EFTu:EFTs increased from 1:6 to 1:2 in patient
      heart, whereas in liver it decreased from 1:1 to 1:4. Over-expression of either
      EFTu or EFTs in control and patient fibroblasts produced dominant negative
      effects, indicating that the relative abundance of these factors is an important
      determinant of translation efficiency. Our results demonstrate marked differences
      among tissues in the organization of the mitochondrial translation system and its
      response to dysfunction, and explain the severe hepatopathy, but normal cardiac
      function in EFG1 patients.

PMID- 16632486
TI  - Association of PINK1 and DJ-1 confers digenic inheritance of early-onset
      Parkinson's disease.
AB  - Mutations in genes encoding both DJ-1 and pten-induced kinase 1 (PINK1) are
      independently linked to autosomal recessive early-onset familial forms of
      Parkinson's disease (PD). We here report identification of a family with PD
      patients harboring novel heterozygous missense mutations in both PINK1 and DJ-1
      genes encoding DJ-1A39S and PINK1P399L, respectively. In transfected cells, DJ-1
      interacts with PINK1. PINK1P399L is less stable than the wild-type protein and is
      degraded via the ubiquitin-mediated proteasomal pathway. Expression of wild-type
      DJ-1 increased steady-state levels of PINK1, whereas expression of DJ-1A39S
      reduced steady-state levels of PINK1. Furthermore, co-expression of wild-type DJ
      1 and PINK1 suppresses neurotoxin 1-methyl-4-phenylpyridinium (MPP(+))-induced
      death of dopaminergic SH-SY5Y cells. In contrast, co-expression of PD-associated
      DJ-1A39S and PINK1P399L significantly potentiated susceptibility of SH-SY5Y cells
      to MPP(+)-induced cell death. This study reports the first case of autosomal
      recessive PD with digenic inheritance and demonstrates that DJ-1 and PINK1
      physically associate and collaborate to protect cells against stress via complex
      formation.

PMID- 16632487
TI  - Persistent presentation of medically unexplained symptoms in general practice.
AB  - OBJECTIVES: To estimate the prevalence of persistent presentation of medically
      unexplained physical symptoms (MUPS) in general practice. To assess socio
      demographic characteristics, health status and use of health services of patients
      who frequently present MUPS, compared with reference groups. DESIGN: One-year,
      nationwide, representative survey of morbidity in general practice in The
      Netherlands, including 400,000 enlisted patients in 104 general practices.
      RESULTS: Of all patients (age: 18 years and older), 2.45% who visited their GP at
      least once a year, presented at least 4 times in 1 year with symptoms which are
      commonly considered medically unexplained without getting a medical diagnosis
      during that period, that might explain the symptoms. These patients are
      significantly older, more often female, less educated, more frequently unemployed
      and more frequently from a non-Western origin than 'average' patients or patients
      with a medical diagnosis. CONCLUSION: Although 25-50% of all reasons for visit to
      a GP concern symptoms that are not medically explained, the frequent presentation
      of such symptoms is much more rare. Frequent attendance because of MUPS is most
      common among elderly women with a lower socio-economic status.

PMID- 16632488
TI  - Modeling, estimation and validation of cotton dust and endotoxin exposures in
      Chinese textile operations.
AB  - In support of an epidemiological study of cancer incidence among cotton textile
      workers in Shanghai, PRC, historical estimates of exposure to cotton dust and
      endotoxin were developed for subjects drawn from a cohort of 267,400 female
      textile workers. A large dataset of historical cotton dust measurements were
      available from 56 of the study factories. Using these data, a series of models
      were developed to estimate cotton dust exposure by year, factory and process.
      Model estimates were validated by comparing with independently collected
      measurements gathered over a 15 year period and indicated a low relative bias (<
      2%) and relative accuracy (+/- 61%). Endotoxin exposures were estimated using the
      endotoxin content of cotton dust by major processes obtained in five separate
      surveys in these factories. The validated exposures were assigned to the 7,242
      jobs held by the 3,812 study subjects. Among the exposed workers, the mean
      cumulative exposure levels were 113.8 mg m(-3)*years for cotton dust and 6,707.7
      EU m(-3)*years for endotoxin, respectively. The overall correlation among cotton
      dust and endotoxin exposures for these subjects was r = 0.58. Using an unusually
      rich set of historical cotton dust measurements, along with independently
      collected exposure measurements for validation and conversion to endotoxin
      levels, validated estimates of cumulative exposure were constructed for this
      large case-cohort study in the textile industry.

PMID- 16632489
TI  - Modified signal-to-noise: a new simple and practical gene filtering approach
      based on the concept of projective adaptive resonance theory (PART) filtering
      method.
AB  - Considering the recent advances in and the benefits of DNA microarray
      technologies, many gene filtering approaches have been employed for the diagnosis
      and prognosis of diseases. In our previous study, we developed a new filtering
      method, namely, the projective adaptive resonance theory (PART) filtering method.
      This method was effective in subclass discrimination. In the PART algorithm, the
      genes with a low variance in gene expression in either class, not both classes,
      were selected as important genes for modeling. Based on this concept, we
      developed novel simple filtering methods such as modified signal-to-noise (S2N')
      in the present study. The discrimination model constructed using these methods
      showed higher accuracy with higher reproducibility as compared with many
      conventional filtering methods, including the t-test, S2N, NSC and SAM. The
      reproducibility of prediction was evaluated based on the correlation between the
      sets of U-test p-values on randomly divided datasets. With respect to leukemia,
      lymphoma and breast cancer, the correlation was high; a difference of >0.13 was
      obtained by the constructed model by using <50 genes selected by S2N'.
      Improvement was higher in the smaller genes and such higher correlation was
      observed when t-test, NSC and SAM were used. These results suggest that these
      modified methods, such as S2N', have high potential to function as new methods
      for marker gene selection in cancer diagnosis using DNA microarray data.
      AVAILABILITY: Software is available upon request.

PMID- 16632490
TI  - A probabilistic dynamical model for quantitative inference of the regulatory
      mechanism of transcription.
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. This task, however, is difficult for a
      number of reasons: transcription factors' expression levels are often low and
      noisy, and many transcription factors are post-transcriptionally regulated. It is
      therefore useful to infer the activity of the transcription factors from the
      expression levels of their target genes. RESULTS: We introduce a novel
      probabilistic model to infer transcription factor activities from microarray data
      when the structure of the regulatory network is known. The model is based on
      regression, retaining the computational efficiency to allow genome-wide
      investigation, but is rendered more flexible by sampling regression coefficients
      independently for each gene. This allows us to determine the strength with which
      a transcription factor regulates each of its target genes, therefore providing a
      quantitative description of the transcriptional regulatory network. The
      probabilistic nature of the model also means that we can associate credibility
      intervals to our estimates of the activities. We demonstrate our model on two
      yeast datasets. In both cases the network structure was obtained using chromatin
      immunoprecipitation data. We show how 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- 16632491
TI  - GeneRecon--a coalescent based tool for fine-scale association mapping.
AB  - GeneRecon is a tool for fine-scale association mapping using a coalescence model.
      GeneRecon takes as input case-control data from phased or unphased SNP and
      microsatellite genotypes. The posterior distribution of disease locus position is
      obtained by Metropolis-Hastings sampling in the state space of genealogies. Input
      format, search strategy and the sampled statistics can be configured through the
      Guile Scheme programming language embedded in GeneRecon, making GeneRecon highly
      configurable. AVAILABILITY: The source code for GeneRecon, written in C++ and
      Scheme, is available under the GNU General Public License (GPL) at
      http://www.birc.au.dk/~mailund/GeneRecon CONTACT: mailund@birc.au.dk.

PMID- 16632492
TI  - Two Sample Logo: a graphical representation of the differences between two sets
      of sequence alignments.
AB  - SUMMARY: Two Sample Logo is a web-based tool that detects and displays
      statistically significant differences in position-specific symbol compositions
      between two sets of multiple sequence alignments. In a typical scenario, two
      groups of aligned sequences will share a common motif but will differ in their
      functional annotation. The inclusion of the background alignment provides an
      appropriate underlying amino acid or nucleotide distribution and addresses
      intersite symbol correlations. In addition, the difference detection process is
      sensitive to the sizes of the aligned groups. Two Sample Logo extends WebLogo, a
      widely-used sequence logo generator. The source code is distributed under the MIT
      Open Source license agreement and is available for download free of charge.

PMID- 16632493
TI  - Molecular complexes at a glance: automated generation of two-dimensional complex
      diagrams.
AB  - MOTIVATION: In this paper a new algorithmic approach is presented, which
      automatically generates structure diagrams of molecular complexes. A complex
      diagram contains the ligand, the amino acids of the protein interacting with the
      ligand and the hydrophilic interactions schematized as dashed lines between the
      corresponding atoms. The algorithm is based on a combinatorial optimization
      strategy which solves parts of the layout problem non-heuristically. The depicted
      molecules are represented as structure diagrams according to the chemical
      nomenclature. Due to the frequent usage of complex diagrams in the scientific
      literature as well as in text books dealing with structural biology, biochemistry
      and medicinal chemistry, the new algorithm is a key element for computer
      applications in these areas. RESULTS: The method was implemented in the new
      software tool PoseView. It was tested on a representative dataset containing 305
      protein-ligand complexes in total from the Brookhaven Protein Data Bank. PoseView
      was able to find collision-free layouts for more than three quarters of all
      complexes. In the following the layout generation algorithm is presented and,
      additional to the statistical results, representative test cases demonstrating
      the challenges of the layout generation will be discussed. AVAILABILITY: The
      method is available as a webservice at http://www.zbh.uni-hamburg.de/poseview.

PMID- 16632494
TI  - A simple implementation of a normal mixture approach to differential gene
      expression in multiclass microarrays.
AB  - MOTIVATION: An important problem in microarray experiments is the detection of
      genes that are differentially expressed in a given number of classes. We provide
      a straightforward and easily implemented method for estimating the posterior
      probability that an individual gene is null. The problem can be expressed in a
      two-component mixture framework, using an empirical Bayes approach. Current
      methods of implementing this approach either have some limitations due to the
      minimal assumptions made or with more specific assumptions are computationally
      intensive. RESULTS: By converting to a z-score the value of the test statistic
      used to test the significance of each gene, we propose a simple two-component
      normal mixture that models adequately the distribution of this score. The
      usefulness of our approach is demonstrated on three real datasets.

PMID- 16632495
TI  - GAME: detecting cis-regulatory elements using a genetic algorithm.
AB  - MOTIVATION: Identification of a transcription factor binding sites is an
      important aspect of the analysis of genetic regulation. Many programs have been
      developed for the de novo discovery of a binding motif (collection of binding
      sites). Recently, a scoring function formulation was derived that allows for the
      comparison of discovered motifs from different programs [S.T. Jensen, X.S. Liu,
      Q. Zhou and J.S. Liu (2004) Stat. Sci., 19, 188-204.] A simple program,
      BioOptimizer, was proposed in [S.T. Jensen and J.S. Liu (2004) Bioinformatics,
      20, 1557-1564.] that improved discovered motifs by optimizing a scoring function.
      However, BioOptimizer is a very simple algorithm that can only make local
      improvements upon an already discovered motif and so BioOptimizer can only be
      used in conjunction with other motif-finding software. RESULTS: We introduce
      software, GAME, which utilizes a genetic algorithm to find optimal motifs in DNA
      sequences. GAME evolves motifs with high fitness from a population of randomly
      generated starting motifs, which eliminate the reliance on additional motif
      finding programs. In addition to using standard genetic operations, GAME also
      incorporates two additional operators that are specific to the motif discovery
      problem. We demonstrate the superior performance of GAME compared with MEME,
      BioProspector and BioOptimizer in simulation studies as well as several real data
      applications where we use an extended version of the GAME algorithm that allows
      the motif width to be unknown.

PMID- 16632496
TI  - Exploiting indirect neighbours and topological weight to predict protein function
      from protein-protein interactions.
AB  - MOTIVATION: Most approaches in predicting protein function from protein-protein
      interaction data utilize the observation that a protein often share functions
      with proteins that interacts with it (its level-1 neighbours). However, proteins
      that interact with the same proteins (i.e. level-2 neighbours) may also have a
      greater likelihood of sharing similar physical or biochemical characteristics. We
      speculate that functional similarity between a protein and its neighbours from
      the two different levels arise from two distinct forms of functional association,
      and a protein is likely to share functions with its level-1 and/or level-2
      neighbours. We are interested in finding out how significant is functional
      association between level-2 neighbours and how they can be exploited for protein
      function prediction. RESULTS: We made a statistical study on recent interaction
      data and observed that functional association between level-2 neighbours is
      clearly observable. A substantial number of proteins are observed to share
      functions with level-2 neighbours but not with level-1 neighbours. We develop an
      algorithm that predicts the functions of a protein in two steps: (1) assign a
      weight to each of its level-1 and level-2 neighbours by estimating its functional
      similarity with the protein using the local topology of the interaction network
      as well as the reliability of experimental sources and (2) scoring each function
      based on its weighted frequency in these neighbours. Using leave-one-out cross
      validation, we compare the performance of our method against that of several
      other existing approaches and show that our method performs relatively well.

PMID- 16632497
TI  - G8: a novel domain associated with polycystic kidney disease and non-syndromic
      hearing loss.
AB  - We report a novel protein domain-G8-which contains five repeated beta-strand
      pairs and is present in some disease-related proteins such as PKHD1, KIAA1199,
      TMEM2 as well as other uncharacterized proteins. Most G8-containing proteins are
      predicted to be membrane-integral or secreted. The G8 domain may be involved in
      extracellular ligand binding and catalysis. It has been reported that mis-sense
      mutations in the two G8 domains of human PKHD1 protein resulted in a less stable
      protein and are associated with autosomal-recessive polycystic kidney disease,
      indicating the importance of the domain structure. G8 is also present in the N
      terminus of some non-syndromic hearing loss disease-related proteins such as
      KIAA1109 and TMEM2. Discovery of G8 domain will be important for the research of
      the structure/function of related proteins and beneficial for the development of
      novel therapeutics. CONTACT: liangsp@hunnu.edu.cn

PMID- 16632499
TI  - A computational protocol for the integration of the monotopic protein
      prostaglandin H2 synthase into a phospholipid bilayer.
AB  - Prostaglandin H2 synthase (PGHS) synthesizes PGH2, a prostaglandin precursor,
      from arachidonic acid and was the first monotopic enzyme to have its structure
      experimentally determined. Both isozymes of PGHS are inhibited by nonsteroidal
      antiinflammatory drugs, an important class of drugs that are the primary means of
      relieving pain and inflammation. Selectively inhibiting the second isozyme, PGHS
      2, minimizes the gastrointestinal side-effects. This had been achieved by the new
      PGHS-2 selective NSAIDs (i.e., COX-2 inhibitors) but it has been recently
      suggested that they suffer from additional side-effects. The design of these
      drugs only made use of static structures from x-ray crystallographic experiments.
      Investigating the dynamics of both PGHS-1 and PGHS-2 using classical molecular
      dynamics is expected to generate new insight into the differences in behavior
      between the isozymes, and therefore may allow improved PGHS-2 selective
      inhibitors to be designed. We describe a molecular dynamics protocol that
      integrates PGHS monomers into phospholipid bilayers, thereby producing in silico
      atomistic models of the PGHS system. Our protocol exploits the vacuum created
      beneath the protein when several lipids are removed from the top leaflet of the
      bilayer. The protein integrates into the bilayer during the first 5 ns in a
      repeatable process. The integrated PGHS monomer is stable and forms multiple
      hydrogen bonds between the phosphate groups of the lipids and conserved basic
      residues (Arg, Lys) on the protein. These interactions stabilize the system and
      are similar to interactions observed for transmembrane proteins.

PMID- 16632500
TI  - DNA diffusion in mucus: effect of size, topology of DNAs, and transfection
      reagents.
AB  - DNA represents a promising therapeutic and prophylactic macromolecule in treating
      genetic diseases, infectious diseases and cancers. The therapeutic potential of
      DNA is directly related to how DNA transports within the targeted tissue. In this
      study, fluorescence photobleaching recovery was used to examine the diffusion of
      plasmid DNAs with various size (2.7-8.3 kb), topology, and in the presence of
      transfection reagents in mucus. We observed that DNAs diffused slower when size
      of DNAs increased; supercoiled DNAs diffused faster than linear ones; mucus did
      not reduce the diffusion of linear DNAs but retarded the diffusion of supercoiled
      DNAs. Diffusion data were fitted to models of a polymer chain diffusing in gel
      systems. Diffusion of linear DNAs in mucus were better described by the Zimm
      model with a scaling factor of -0.8, and supercoiled DNAs showed a reptational
      behavior with a scaling factor of -1.3. Based on the Zimm model, the pore size of
      bovine mucus was estimated and agreed well with previous experimental data. In
      the presence of transfection reagents, e.g., liposomes, the diffusion of DNAs
      increased by a factor of 2 in mucus. By using bovine mucus as a model system,
      this work suggests that DNA size, topology, and the presence of transfection
      reagents may affect the diffusion of DNA in tissues, and thus the therapeutic
      effects of DNA.

PMID- 16632501
TI  - Nonperturbative chemical imaging of organelle transport in living cells with
      coherent anti-stokes Raman scattering microscopy.
AB  - Nonperturbative monitoring of intracellular organelle transport in unstained
      living cells was achieved with coherent anti-Stokes Raman scattering (CARS)
      microscopy. To avoid possible interference with the organelle transport
      introduced by laser radiation, we first examined different illumination
      conditions. Using a new photodamage criterion based on morphological changes of
      the cells, we determined the threshold values of both pulse energy and average
      power at relevant wavelengths. Under excitation conditions much milder than the
      threshold levels, we were able to monitor the motions of lipid droplet (LD)
      organelles in steroidogenic mouse adrenal cortical (Y-1) cells with CARS
      microscopy in real time without perturbations to the cells. Particle tracking
      analyses revealed subdiffusion as well as active transport of LDs along
      microtubules. Interestingly, LD active transport is only present in Y-1 cells
      that rounded up in culture, a morphological change associated with
      steroidogenesis, suggesting possible involvements of LD active transport in the
      latter. Simultaneous imaging of LDs and mitochondria with CARS and two-photon
      fluorescence microscopy clearly showed that interactions between the two
      organelles could be facilitated by high LD motility. These observations
      demonstrate CARS microscopy as a powerful noninvasive imaging tool for studying
      dynamic processes in living cells.

PMID- 16632502
TI  - Simultaneous multicolor fluorescence cross-correlation spectroscopy to detect
      higher order molecular interactions using single wavelength laser excitation.
AB  - Fluorescence cross-correlation spectroscopy is a powerful method for the study of
      molecular interactions and dynamics in solution and even in living cells.
      Usually, in the optical setup, either two laser beams have to be superimposed in
      their respective confocal volumes or two-photon excitation is used for a dual
      color detection system. It has been shown recently that fluorescence cross
      correlation can be achieved with spectrally similar fluorophores using single
      wavelength excitation fluorescence cross-correlation spectroscopy (SW-FCCS). In
      this study, we show that SW-FCCS allows the simultaneous excitation of up to
      three fluorophores in which the cross correlation of their fluctuation signals is
      detected separately in three detection channels. The experimental and theoretical
      model to describe triple pairwise cross correlations incorporating cross talk and
      possible changes in emission characteristics such as quenching upon binding are
      outlined. The effectiveness of SW-FCCS to detect binding of three interacting
      partners is experimentally verified with a standard ligand-receptor model, biotin
      streptavidin, where differently labeled biotin ligands and their binding to a
      third-color labeled streptavidin are studied. The cross-correlation amplitudes
      and their changes with stoichiometric binding are analyzed and the upper limits
      of dissociation constants are determined. Performed with appropriate negative
      controls, SW-FCCS can determine interaction patterns between ligands and
      receptors.

PMID- 16632503
TI  - Lipid specificity of surfactant protein B studied by time-of-flight secondary ion
      mass spectrometry.
AB  - One of the key functions of mammalian pulmonary surfactant is the reduction of
      surface tension to minimal values. To fulfill this function it is expected to
      become enriched in dipalmitoylphosphatidylcholine either on its way from the
      alveolar type II pneumocytes to the air/water interface of the lung or within the
      surface film during compression and expansion of the alveoli during the breathing
      cycle. One protein that may play a major role in this enrichment process is the
      surfactant protein B. The aim of this study was to identify the lipidic
      interaction partner of this protein. Time-of-flight secondary ion mass
      spectrometry was used to analyze the lateral distribution of the components in
      two SP-B-containing model systems. Either native or partly isotopically labeled
      lipids were analyzed. The results of both setups give strong indications that, at
      least under the specific conditions of the chosen model systems (e.g., concerning
      pH and lipid composition), the lipid interacting with surfactant protein B is not
      phosphatidylglycerol as generally accepted, but dipalmitoylphosphatidylcholine
      instead.

PMID- 16632504
TI  - Gap-junctional single-channel permeability for fluorescent tracers in mammalian
      cell cultures.
AB  - We have developed a simple dye transfer method that allows quantification of the
      gap-junction permeability of small cultured cells. Fluorescent dyes (calcein and
      Lucifer yellow) were perfused into one cell of an isolated cell pair using a
      patch-type micropipette in the tight-seal whole cell configuration. Dye spreading
      into the neighboring cells was monitored using a low-light charge-coupled device
      camera. Permeation rates for calcein and Lucifer yellow were then estimated by
      fitting the time course of the fluorescence intensities in both cells. For curve
      fitting, we used a set of model equations derived from a compartment model of dye
      distribution. The permeation rates were correlated to the total ionic conductance
      of the gap junction measured immediately after the perfusion experiment. Assuming
      that dye permeation is through a unit-conductance channel, we were then able to
      calculate the single-channel permeance for each tracer dye. We have applied this
      technique to HeLa cells stably transfected with rat-Cx46 and Cx43, and to
      BICR/M1R(k) cells, a rat mammary tumor cell line that has very high dye coupling
      through endogenous Cx43 channels. Scatter plots of permeation rates versus
      junctional conductance did not show a strictly linear correlation of ionic versus
      dye permeance, as would have been expected for a simple pore. Instead, we found
      that the data scatter within a wide range of different single-channel permeances.
      In BICR/M1R(k) cells, the lower limiting single-channel permeance is 2.2 +/- 2.0
      x 10(-12) mm3/s and the upper limit is 50 x 10(-12) mm3/s for calcein and 6.8 +/-
      2.8 x 10(-12) mm3/s and 150 x 10(-12) mm3/s for Lucifer yellow, respectively. In
      HeLa-Cx43 transfectants we found 2.0 +/- 2.4 x 10(-12) mm3/s and 95 x 10(-12)
      mm3/s for calcein and 2.1 +/- 6.8 x 10(-12) mm3/s and 80 x 10(-12) mm3/s for
      Lucifer yellow, and in HeLa-Cx46 transfectants 1.7 +/- 0.3 x 10(-12) mm3/s and
      120 x 10(-12) mm3/s for calcein and 1.3 +/- 1.1 x 10(-12) mm3/s and 34 x 10(-12)
      mm3/s for Lucifer yellow, respectively. This variability is most likely due to a
      yet unknown mechanism that differentially regulates single-channel permeability
      for larger molecules and for small inorganic ions.

PMID- 16632505
TI  - Assisting the reactivation of guanidine hydrochloride-denatured aminoacylase by
      hydroxypropyl cyclodextrins.
AB  - Cyclodextrin is a water-soluble circular oligosaccharide with a cylinder shape
      characterized by exterior hydrophilic rims and an interior hydrophobic cavity,
      which makes it an ideal additive to prevent proteins from aggregating during
      refolding. In this research, three hydroxypropyl cyclodextrins (HPCDs), HP-alpha
      , beta-, and gamma-CD, were used to investigate the molecular mechanism of their
      effects on assisting aminoacylase refolding. The aggregation and reactivation
      experiments suggested that at moderate concentrations, HPCDs could suppress
      aggregation and assist aminoacylase refolding in a concentration-dependent
      manner, and HP-beta-CD was the most efficient of the three HPCDs. Low
      concentrations of HP-alpha-CD and high concentrations of HP-gamma-CD promoted off
      pathway aggregation. Spectroscopic studies indicated that the hydrophobic
      exposure of the unstructured species in the refolded solutions was gradually
      reduced by the three HPCDs with the efficiency HP-beta-CD > HP-gamma-CD > HP
      alpha-CD. Furthermore, the fast phase of aminoacylase reactivation was slowed
      down by the addition of 75 mM HP-beta- and gamma-CD, but no significant effect
      was observed for HP-alpha-CD. The dissimilarity in the effects of the three HPCDs
      suggested that the internal cavity size played a crucial role in their
      antiaggregation ability. Further analysis suggested that the observations might
      be much more complicated than expected because of the various types of
      interactions between cyclodextrins and proteins in addition to their ability to
      bind to protein aromatic residues.

PMID- 16632506
TI  - Thermodynamic equilibrium of domains in a two-component Langmuir monolayer.
AB  - This [corrected] article outlines the results from a combined experimental and
      theoretical study on the properties of circular domains in a mixed Langmuir
      monolayer at thermodynamic equilibrium. The mixed monolayer consisted of a binary
      mixture of dimyristoyl-phosphatidyl-choline and dihydrocholesterol. A long-term
      fluorescence microscopy study of these domains was carried out over the course of
      approximately 60 h. Image analysis of the domains over time revealed that the
      domains ripened slowly with an [corrected] increase in mean domain radius and a
      [corrected] decrease in domain number density. At the end of the measurement, the
      domains remained polydisperse, and true thermodynamic equilibrium was not
      reached. Theoretically, collective thermodynamic equilibrium properties such as
      mean domain size and size distribution were calculated by combining micelle self
      assembly theory and the "equivalent dipole" model for the self-energy of two
      dimensional domains. The calculations predicted existence of finite-sized
      circular domains at equilibrium. This suggests that equilibrium circular
      monolayer domains of single- or multicomponent lipids with a finite size
      distribution should form only at very limited experimental conditions. Both the
      predicted mean domain size and size distribution are strongly affected by line
      tension and dipole moment density difference. A comparison between the
      theoretical and experimental results is made.

PMID- 16632507
TI  - Method of x-ray anomalous diffraction for lipid structures.
AB  - The structures of the unit cells of lipid phases that exhibit long-range
      crystalline order but short-range liquid-like disorder are of biological
      interests. In particular, the recently discovered rhombohedral phase has a unit
      cell containing either the structure of a membrane fusion intermediate state or
      that of a peptide-induced transmembrane pore, depending on the lipid composition
      and participating peptides. Diffraction from such systems generally presents a
      difficult phase problem. The existing methods of phase determination all have
      their limitations. Therefore it is of general interest to develop a new phasing
      method. The method of multi-wavelength anomalous dispersion is routinely used in
      protein crystallography, but the same method is difficult for lipid systems for
      the practical reason that the commonly used lipid samples for diffraction do not
      have a well-defined thickness. Here we describe a practical approach to use the
      multi-wavelength anomalous dispersion method for lipid structures. The procedure
      is demonstrated with the lamellar phase of a brominated lipid. The method is
      general to all phases as long as anomalous diffraction is applicable.

PMID- 16632508
TI  - Mechanical properties of murine leukemia virus particles: effect of maturation.
AB  - After budding from the host cell, retroviruses undergo a process of internal
      reorganization called maturation, which is prerequisite to infectivity. Viral
      maturation is accompanied by dramatic morphological changes, which are poorly
      understood in physical/mechanistic terms. Here, we study the mechanical
      properties of live mature and immature murine leukemia virus particles by
      indentation-type experiments conducted with an atomic force microscope tip. We
      find that both mature and immature particles have an elastic shell. Strikingly,
      the virus shell is twofold stiffer in the immature (0.68 N/m) than the mature
      (0.31 N/m) form. However, finite-element simulation shows that the average
      Young's modulus of the immature form is more than fourfold lower than that of the
      mature form. This finding suggests that per length unit, the protein-protein
      interactions in the mature shell are stronger than those in the immature shell.
      We also show that the mature virus shell is brittle, since it can be broken by
      application of large loading forces, by firm attachment to a substrate, or by
      repeated application of force. Our results are the first analysis of the
      mechanical properties of an animal virus, and demonstrate a linkage between virus
      morphology and mechanical properties.

PMID- 16632509
TI  - Dynamic protein domains: identification, interdependence, and stability.
AB  - Existing methods of domain identification in proteins usually provide no
      information about the degree of domain independence and stability. However, this
      information is vital for many areas of protein research. The recently developed
      hierarchical clustering of correlation patterns (HCCP) technique provides machine
      based domain identification in a computationally simple and physically consistent
      way. Here we present the modification of this technique, which not only allows
      determination of the most plausible number of dynamic domains but also makes it
      possible to estimate the degree of their independence (the extent of correlated
      motion) and stability (the range of environmental conditions, where domains
      remain intact). With this technique we provided domain assignments and calculated
      intra- and interdomain correlations and interdomain energies for >2500 test
      proteins. It is shown that mean intradomain correlation of motions can serve as a
      quantitative criterion of domain independence, and the HCCP stability gap is a
      measure of their stability. Our data show that the motions of domains with high
      stability are usually independent. In contrast, the domains with moderate
      stability usually exhibit a substantial degree of correlated motions. It is shown
      that in multidomain proteins the domains are most stable if they are of similar
      size, and this correlates with the observed abundance of such proteins.

PMID- 16632510
TI  - Characterization of the structure of RAMP1 by mutagenesis and molecular modeling.
AB  - Receptor activity modifying proteins (RAMPs) are a family of single-pass
      transmembrane proteins that dimerize with G-protein-coupled receptors. They may
      alter the ligand recognition properties of the receptors (particularly for the
      calcitonin receptor-like receptor, CLR). Very little structural information is
      available about RAMPs. Here, an ab initio model has been generated for the
      extracellular domain of RAMP1. The disulfide bond arrangement (Cys27-Cys82, Cys40
      Cys72, and Cys57-Cys104) was determined by site-directed mutagenesis. The
      secondary structure (alpha-helices from residues 29-51, 60-80, and 87-100) was
      established from a consensus of predictive routines. Using these constraints, an
      assemblage of 25,000 structures was constructed and these were ranked using an
      all-atom statistical potential. The best 1000 conformations were energy
      minimized. The lowest scoring model was refined by molecular dynamics simulation.
      To validate our strategy, the same methods were applied to three proteins of
      known structure; PDB:1HP8, PDB:1V54 chain H (residues 21-85), and PDB:1T0P. When
      compared to the crystal structures, the models had root mean-square deviations of
      3.8 A, 4.1 A, and 4.0 A, respectively. The model of RAMP1 suggested that Phe93,
      Tyr100, and Phe101 form a binding interface for CLR, whereas Trp74 and Phe92 may
      interact with ligands that bind to the CLR/RAMP1 heterodimer.

PMID- 16632511
TI  - Inhibition of cAMP-dependent protein kinase under conditions occurring in the
      cardiac dyad during a Ca2+ transient.
AB  - The space between the t-tubule invagination and the sarcoplasmic reticulum (SR)
      membrane, the dyad, in ventricular myocytes has been predicted to experience very
      high [Ca2+] for short periods of time during a Ca2+ transient. The dyadic space
      accommodates many protein kinases responsible for the regulation of Ca2+ handling
      proteins of the cell. We show in vitro that cAMP-dependent protein kinase (PKA)
      is inhibited by high [Ca2+] through a shift in the ratio of CaATP/MgATP toward
      CaATP. We further generate a three-dimensional mathematical model of Ca2+ and ATP
      diffusion within dyad. We use this model to predict the extent to which PKA would
      be inhibited by an increased CaATP/MgATP ratio during a Ca2+ transient in the
      dyad in vivo. Our results suggest that under normal physiological conditions a
      myocyte paced at 1 Hz would experience up to 55% inhibition of PKA within the
      cardiac dyad, with inhibition averaging 5% throughout the transient, an effect
      which becomes more pronounced as the myocyte contractile frequency increases (at
      7 Hz, PKA inhibition averages 28% across the dyad throughout the duration of a
      Ca2+ transient).

PMID- 16632512
TI  - FRET study of membrane proteins: simulation-based fitting for analysis of
      membrane protein embedment and association.
AB  - A new formalism for the simultaneous determination of the membrane embedment and
      aggregation of membrane proteins is developed. This method is based on steady
      state Forster (or fluorescence) resonance energy transfer (FRET) experiments on
      site-directed fluorescence labeled proteins in combination with global data
      analysis utilizing simulation-based fitting. The simulation of FRET was validated
      by a comparison with a known analytical solution for energy transfer in idealized
      membrane systems. The applicability of the simulation-based fitting approach was
      verified on simulated FRET data and then applied to determine the structural
      properties of the well-known major coat protein from bacteriophage M13
      reconstituted into unilamellar DOPC/DOPG (4:1 mol/mol) vesicles. For our purpose,
      the cysteine mutants Y24C, G38C, and T46C of this protein were produced and
      specifically labeled with the fluorescence label AEDANS. The energy transfer data
      from the natural tryptophan at position 26, which is used as a donor, to AEDANS
      were analyzed assuming a helix model for the transmembrane domain of the protein.
      As a result of the FRET data analysis, the topology and bilayer embedment of this
      domain were quantitatively characterized. The resulting tilt of the transmembrane
      helix of the protein is 18 +/- 2 degrees. The tryptophan is located at a distance
      of 8.5 +/- 0.5 A from the membrane center. No specific aggregation of the protein
      was found. The methodology developed here is not limited to M13 major coat
      protein and can be used in principle to study the bilayer embedment of any small
      protein with a single transmembrane domain.

PMID- 16632513
TI  - Gradual change or phase transition: characterizing fluid lipid-cholesterol
      membranes on the basis of thermal volume changes.
AB  - Cholesterol has been reported to govern biomembrane permeability, elasticity, and
      the formation of lipid rafts. There has been a controversy whether binary lipid
      cholesterol membranes should better be described in terms of a phase separation
      (liquid-ordered and liquid-disordered phases) or of gradual changes in largely
      homogeneous membranes. We present a new approach for detecting and characterizing
      phase equilibria in colloidal dispersions using pressure perturbation calorimetry
      (PPC). We apply this to the study of the thermal expansivity of mixtures of 1
      palmitoyl-2-oleoyl sn-glycero-3-phosphatidylcholine (POPC) and cholesterol as a
      function of composition and temperature. We show that cholesterol can condense
      lipids not only laterally (with respect to interfacial area) but also in volume.
      A quantitative comparison with expansivity curves simulated assuming either phase
      separation or random mixing within one phase reveals that the real system shows
      an intermediate behavior due to submicroscopic demixing effects. However, both
      models yield consistent system parameters and are thus found to be useful for
      describing the systems to a similar approximation. Accordingly, one cholesterol
      may condense 3 +/- 1 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine
      molecules by approximately -(1.4 +/- 0.5) vol % at 2 degrees C; both absolute
      values decrease with increasing temperature.

PMID- 16632514
TI  - Mechanism of titin unfolding by force: insight from quasi-equilibrium molecular
      dynamics calculations.
AB  - We have studied the unfolding by force of one of the immunoglobulin domains of
      the muscle protein titin using molecular dynamics simulations at 300 K. Previous
      studies, done at constant pulling rates, showed that under the effect of the
      force two strands connected to each other by six backbone H-bonds are pulled
      apart. No details about the mechanism of H-bond breaking were provided. Our
      simulation protocol "pull and wait" was designed to correspond to very slow
      pulling, more similar to the rates used in experiments than are the protocols
      used in previous computational studies. Under these conditions interstrand
      backbone H-bonds are not "ripped apart" by the application of the force. Instead,
      small elongations produced by the force weaken specific backbone H-bonds with
      respect to water-backbone H-bonds. These weakened bonds allow a single water
      molecule to make H-bonds to the CO and the NH of the same backbone H-bond while
      they are still bound to each other. The backbone H-bond then breaks (distance >
      3.6 A), but its donor and acceptor atoms remain bound to the same water molecule.
      Further separation of the chains takes place when a second water molecule makes
      an H-bond with either the protein backbone donor or acceptor atom. Thus, the
      force does not directly break the main chain H-bonds: it destabilizes them in
      such a way that they are replaced by H-bonds to water. With this mechanism, the
      force necessary to break all the H-bonds required to separate the two strands
      will be strongly dependent on the pulling speed. Further simulations carried out
      at low forces but long waiting times (> or = 500 ps, < or = 10 ns) show that,
      given enough time, even a very small pulling force (< 400 pN) is sufficient to
      destabilize the interstrand H-bonds and allow them to be replaced by H-bonds to
      two water molecules. As expected, increasing the temperature to 350 K allows the
      interstrand H-bonds to break at lower forces than those required at 300 K.

PMID- 16632515
TI  - Adjusting batch effects in microarray expression data using empirical Bayes
      methods.
AB  - Non-biological experimental variation or "batch effects" are commonly observed
      across multiple batches of microarray experiments, often rendering the task of
      combining data from these batches difficult. The ability to combine microarray
      data sets is advantageous to researchers to increase statistical power to detect
      biological phenomena from studies where logistical considerations restrict sample
      size or in studies that require the sequential hybridization of arrays. In
      general, it is inappropriate to combine data sets without adjusting for batch
      effects. Methods have been proposed to filter batch effects from data, but these
      are often complicated and require large batch sizes ( > 25) to implement. Because
      the majority of microarray studies are conducted using much smaller sample sizes,
      existing methods are not sufficient. We propose parametric and non-parametric
      empirical Bayes frameworks for adjusting data for batch effects that is robust to
      outliers in small sample sizes and performs comparable to existing methods for
      large samples. We illustrate our methods using two example data sets and show
      that our methods are justifiable, easy to apply, and useful in practice. Software
      for our method is freely available at: http://biosun1.harvard.edu/complab/batch/.

PMID- 16632516
TI  - Physiological effects of oxidized exogenous surfactant in vivo: effects of high
      tidal volume and surfactant protein A.
AB  - Oxidative damage to surfactant can decrease lung function in vivo. In the current
      study, our two objectives were: 1) to examine whether the adverse effects of
      oxidized surfactant would be accentuated in animals exposed to high tidal volume
      ventilation, and 2) to test whether supplementation with surfactant protein A (SP
      A) could improve the function of oxidized surfactant in vivo. The first objective
      was addressed by evaluating the response of surfactant-deficient rats
      administered normal or oxidized surfactant and then subjected to low tidal volume
      (6 ml/kg) or high tidal volume (12 ml/kg) mechanical ventilation. Under low tidal
      volume conditions, rats administered oxidized surfactant had impaired lung
      function, as determined by lung compliance and arterial blood gas analysis,
      compared with nonoxidized controls. Animals subjected to high tidal volume
      ventilation had impaired lung function compared with low tidal volume groups,
      regardless of the oxidative status of the surfactant. The second experiment
      demonstrated a significantly superior physiological response in surfactant
      deficient rats receiving SP-A containing oxidized surfactant compared with
      oxidized surfactant. Lavage analysis at the end of the in vivo experimentation
      showed no differences in the recovery of oxidized surfactant compared with
      nonoxidized surfactant. We conclude that minimizing excessive lung stretch during
      mechanical ventilation is important in the context of exogenous surfactant
      supplementation and that SP-A has an important biophysical role in surfactant
      function in conditions of oxidative stress. Furthermore, the oxidative status of
      the surfactant does not appear to affect the alveolar metabolism of this
      material.

PMID- 16632517
TI  - Neutrophil elastase induces IL-8 gene transcription and protein release through
      p38/NF-{kappa}B activation via EGFR transactivation in a lung epithelial cell
      line.
AB  - In this study, we investigated the regulation and mechanism of IL-8 expression by
      A549 human lung carcinoma cells treated with neutrophil elastase (NE). NE-treated
      cells exhibited significantly higher IL-8 protein levels in culture media
      compared with cells treated with vehicle alone. Blocking of gene transcription
      with actinomycin D suggested that NE stimulated IL-8 synthesis via increased mRNA
      expression, which was verified by real-time RT-PCR. NE activated the IL-8
      promoter but did not alter the stability of its mRNA, confirming that the
      protease induced IL-8 synthesis through increased gene transcription. The results
      from the use of chemical inhibitors and mutant gene constructs against various
      signal transduction components seem to suggest the linear signaling pathway
      involving the activation of PKC-delta --> dual oxidase 1 --> reactive oxygen
      species --> TNF-alpha-converting enzyme --> EGF receptor --> p38 --> NF-kappaB
      for NE-activated IL-8 gene expression. A NF-kappaB potential binding site,
      located between nucleotides -82 and -69 of the IL-8 promoter, was identified as
      necessary for NE-induced IL-8 transcription. We conclude that NE increases IL-8
      transcription through p38/NF-kappaB activation via EGFR transactivation.

PMID- 16632518
TI  - Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK
      dependent pathways.
AB  - Extracellular nucleotides can mediate a variety of cellular functions via
      interactions with purinergic receptors. We previously showed that mechanical
      ventilation (MV) induces airway IL-6 and ATP release, modifies luminal nucleotide
      composition, and alters lung purinoceptor expression. Here we hypothesize that
      extracellular nucleotides induce secretion of IL-6 by small airway epithelial
      cells (SAEC). Human SAEC were stimulated with nucleotides in the presence or
      absence of inhibitors. Supernatants were analyzed for IL-6 and lysates for p38
      MAPK activity by ELISA. RNA was analyzed by real-time RT-PCR. Rats (n=51) were
      randomized to groups as follows: control, small-volume MV, large-volume MV, large
      volume MV-intratracheal apyrase, or small-volume MV-intratracheal adenosine 5'-O
      (3-thiotriphosphate) (ATPgammaS). After 1 h of MV, bronchoalveolar lavage fluid
      was analyzed for ATP and IL-6 by luminometry and ELISA. ATP and ATPgammaS
      increased SAEC IL-6 secretion in a time- and dose-dependent manner, an effect
      inhibited by apyrase. Agonists were ranked in the following order:
      ATPgammaS>ATP=UTP>ADP=adenosine>2-methylthio-ADP=control. SB-203580, but not U
      0126 or JNK1 inhibitor, decreased nucleotide effects. Additionally, nucleotides
      induced p38 MAPK phosphorylation. Inhibitors of Ca2+ signaling, phospholipase C,
      transcription, and translation decreased IL-6 release. Furthermore, nucleotides
      increased IL-6 expression. In vivo, large-volume MV increased airway ATP and IL-6
      concentrations. IL-6 release was decreased by apyrase and increased by ATPgammaS.
      Extracellular nucleotides induce P2Y2-mediated secretion of IL-6 by SAEC via
      Ca2+, phospholipase C, and p38 MAPK-dependent pathways. This effect is dependent
      on transcription and translation. Our findings were confirmed in an in vivo
      model, thus demonstrating a novel mechanism of nucleotide-induced IL-6 secretion
      by airway epithelia.

PMID- 16632519
TI  - BK channel beta1-subunit regulation of calcium handling and constriction in
      tracheal smooth muscle.
AB  - The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage
      dependent Ca2+ entry in many cell types. The BK channel accessory beta1-subunit
      promotes channel activation in smooth muscle and is required for proper tone in
      the vasculature and bladder. However, although BK channels have also been
      implicated in airway smooth muscle function, their regulation by the beta1
      subunit has not been investigated. Utilizing the gene-targeted mice for the beta1
      subunit gene, we have investigated the role of the beta1-subunit in tracheal
      smooth muscle. In mice with the beta1-subunit-knockout allele, BK channel
      activity was significantly reduced in excised tracheal smooth muscle patches and
      spontaneous BK currents were reduced in whole tracheal smooth muscle cells.
      Knockout of the beta1-subunit resulted in an increase in resting Ca2+ levels and
      an increase in the sustained component of Ca2+ influx after cholinergic
      signaling. Tracheal constriction studies demonstrate that the level of
      constriction is the same with knockout of the beta1-subunit and BK channel block
      with paxillin, indicating that BK channels contribute little to airway relaxation
      in the absence of the beta1-subunit. Utilizing nifedipine, we found that the
      increased constriction caused by knockout of the beta1-subunit could be accounted
      for by an increased recruitment of L-type voltage-dependent Ca2+ channels. These
      results indicate that the beta1-subunit is required in airway smooth muscle for
      control of voltage-dependent Ca2+ influx during rest and after cholinergic
      signaling in BK channels.

PMID- 16632520
TI  - CFTR gene therapy, a method to rescue lung hypoplasia in congenital diaphragmatic
      hernia?

PMID- 16632521
TI  - Surface tension influences cell shape and phagocytosis in alveolar macrophages.
AB  - The effect of surface tension on alveolar macrophage shape and phagocytosis was
      assessed in vivo and in vitro. Surface tension was regulated in vivo by
      conditionally expressing surfactant protein (SP)-B in Sftpb-/- mice. Increased
      surface tension and respiratory distress were produced by depletion of SP-B and
      were readily reversed by repletion of SP-B in vivo. Electron microscopy was used
      to demonstrate that alveolar macrophages were usually located beneath the
      surfactant film on the alveolar surfaces. Reduction of SP-B increased surface
      tension and resulted in flattening of alveolar macrophages on epithelial surfaces
      in vivo. Phagocytosis of intratracheally injected fluorescent microbeads by
      alveolar macrophages was decreased during SP-B deficiency and was restored by
      repletion of SP-B in vivo. Incubation of MH-S cells, a mouse macrophage cell
      line, with inactive surfactant caused cell flattening and decreased phagocytosis
      in vitro, findings that were reversed by the addition of sheep surfactant or
      phospholipid containing SP-B. SP-B controls surface tension by forming a
      surfactant phospholipid film that regulates shape and nonspecific phagocytic
      activity of alveolar macrophages on the alveolar surface.

PMID- 16632522
TI  - Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent
      pathways.
AB  - Xanthine oxidoreductase (XOR) plays a prominent role in acute lung injury because
      of its ability to generate reactive oxygen species. We investigated the role of
      XOR in ventilator-induced lung injury (VILI). Male C57BL/6J mice were assigned to
      spontaneous ventilation (sham) or mechanical ventilation (MV) with low (7 ml/kg)
      and high tidal volume (20 ml/kg) for 2 h after which lung XOR activity and
      expression were measured and the effect of the specific XOR inhibitor allopurinol
      on pulmonary vascular leakage was examined. In separate experiments, rat
      pulmonary microvascular endothelial cells (RPMECs) were exposed to cyclic stretch
      (5% and 18% elongation, 20 cycles/min) for 2 h before intracellular XOR activity
      measurement. Lung XOR activity was significantly increased at 2 h of MV without
      changes in XOR expression. There was evidence of p38 MAP kinase, ERK1/2, and ERK5
      phosphorylation, but no change in JNK phosphorylation. Evans blue dye
      extravasation and bronchoalveolar lavage protein concentration were significantly
      increased in response to MV, changes that were significantly attenuated by
      pretreatment with allopurinol. Cyclic stretch of RPMECs also caused MAP kinase
      phosphorylation and a 1.7-fold increase in XOR activity, which was completely
      abrogated by pretreatment of the cells with specific MAP kinase inhibitors. We
      conclude that XOR enzymatic activity is significantly increased by mechanical
      stress via activation of p38 MAP kinase and ERK and plays a critical role in the
      pathogenesis of pulmonary edema associated with VILI.

PMID- 16632523
TI  - Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4
      activity in Huh7 human hepatoma cells.
AB  - Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR)
      dimerizes with retinoid X receptor (RXR) and regulates the transcription of genes
      encoding xenobiotic-metabolizing enzymes such as CYP3A4. Rifampin, the classical
      activator of CYP3A4, binds to SXR directly. It is unclear whether various natural
      and synthetic retinoids can regulate the expression of CYP3A4. To evaluate the
      effects of retinoids on the RXR/SXR-mediated pathway, transient transfection
      assays were performed on both CV-1 and human hepatoma Huh7 cells using a reporter
      construct containing multiple RXR/SXR consensus binding elements (an everted
      repeat with a 6-nucleotide spacer, ER-6). The results revealed that eight out of
      13 retinoids screened significantly induced the RXR/SXR-mediated pathway in Huh7
      cells. At an equal molar concentration, the acid forms (9-cis-RA, 13-cis-RA, and
      all-trans-RA) or aldehyde, the direct precursor of acid (9-cis-retinal and 13-cis
      retinal), exhibited a greater or similar potency than rifampin. Depending on the
      ligands, RXR may serve as a silent or an active partner of SXR. Additionally,
      retinoids can increase CYP3A4 enzyme activity in Huh7 cells. To further evaluate
      the potential drug-drug interactions, which may be caused by retinoids, Huh7
      cells were pretreated with 9-cis-RA and followed by acetaminophen. We showed that
      9-cis-RA enhanced the covalent binding of N-acetyl-p-quinoneimine, a toxic
      intermediate of acetaminophen produced by phase I enzymes oxidation. This result
      suggested that drug-drug interaction might occur between 9-cis-RA and
      acetaminophen in human liver cells. Taken together, retinoids activate the
      RXR/SXR-mediated pathway and regulate the expression of CYP3A4. Thus, retinoids
      potentially can cause drug-drug interactions when they are administered with
      other CYP3A4 substrates.

PMID- 16632525
TI  - Survey of the prevalence, diagnosis and treatment of dermatological conditions in
      small animals in general practice.
AB  - A survey was made of the prevalence, diagnosis and treatment of dermatological
      conditions in small animals in general practice in the UK. Out of 3707 small
      animal consultations in general practice that were observed and recorded, 795
      (21.4 per cent) involved animals that had a dermatological problem. In dogs and
      exotic species, pruritus was the most common presenting sign, accounting for 30
      to 40 per cent of the dermatological consultations. In cats, cutaneous swellings
      were the most common presentation (36 per cent). A diagnosis or recommendation
      for treatment was made on the basis of the presenting clinical signs and physical
      examination alone in 576 (72 per cent) of the cases, and various diagnostic tests
      were performed in the other cases. In dogs, parasitic infestations, bacterial
      infections and neoplasia accounted for the majority of the diagnoses. In cats,
      parasites and bacterial infections were the most common. In exotic species,
      parasites accounted for over 80 per cent of the dermatological diagnoses. In
      dogs, the most common final diagnoses were otitis, pyoderma, anal sac impaction,
      flea infestation and atopic dermatitis. In cats, abscesses, flea infestation, and
      otitis were the most common diagnoses. In exotic species, the most common
      diagnosis was an unspecified mite infestation. Systemic antibiotics were
      prescribed in 196 cases (25 per cent), systemic glucocorticoids were prescribed
      in 162 cases (20 per cent) and treatment with an ectoparasiticide was prescribed
      in 167 cases (21 per cent).

PMID- 16632526
TI  - Seroprevalence of antibodies to Encephalitozoon cuniculi in domestic rabbits in
      the United Kingdom.
AB  - Serum samples from 97 clinically healthy domestic rabbits were tested for
      antibodies to Encephalitozoon cuniculi by an indirect elisa technique. Fifty (52
      per cent) of them were seropositive. The samples were taken as part of a routine
      health screen or before general anaesthesia at 22 veterinary practices in
      England, Scotland and Wales, and the veterinary surgeons were asked to complete a
      questionnaire to provide information concerning the animal's husbandry, diet,
      vaccination, health status and any preventive medicine routines. None of these
      factors was found to be associated with the serological status of the rabbits.

PMID- 16632527
TI  - Lethal outbreak of disease associated with feline calicivirus infection in cats.
AB  - Recently, in the USA, virulent mutants of feline calicivirus (FCV) have been
      identified as the cause of a severe and acute virulent systemic disease,
      characterised by jaundice, oedema and high mortality in groups of cats. This
      severe manifestation of FCV disease has so far only been reported in the USA.
      However, in 2003, an outbreak of disease affected a household of four adult cats
      and an adult cat from a neighbouring household in the UK. Three of the adult cats
      in the household and the neighbouring cat developed clinical signs including
      pyrexia (39.5 to 40.5 degrees C), lameness, voice loss, inappetence and jaundice.
      One cat was euthanased in extremis, two died and one recovered. A postmortem
      examination of one of the cats revealed focal cellulitis around the right hock
      and right elbow joints. The principal finding of histopathological examinations
      of selected organs from two of the cats was disseminated hepatocellular necrosis
      with mild inflammatory infiltration. Immunohistology identified FCV antigen in
      parenchymal and Kupffer cells in the liver of both animals and in alveolar
      macrophages of one of them. In addition, calicivirus-like particles were observed
      by electron microscopy within the hepatocytes of one cat. FCV was isolated from
      two of the dead cats and from the two surviving cats. Sequence analysis showed
      that they were all infected with the same strain of virus, but that it was
      different from strains of FCV associated with the virulent systemic disease in
      cats in the USA. The outbreak was successfully controlled by quarantine in the
      owner's house.

PMID- 16632528
TI  - Controlled trial of behavioural therapy for separation-related disorders in dogs.
AB  - A generic programme of behavioural modification for the clinical treatment of
      separation-related behaviours in dogs was assessed in a controlled replicated
      trial. After 12 weeks of treatment, 56 per cent of the owners of the treated dogs
      reported significant improvements in their dogs' behaviour, and a further 25 per
      cent reported a slight improvement. The owners' reports were generally supported
      by changes in the behaviour of the dogs as recorded on video when they were left
      alone. The majority of the untreated dogs continued to show the same degree of
      separation-related behaviour throughout the 12 weeks of the trial. In a
      supplementary set of 30 case studies, treated with a behavioural programme
      tailored to the specific diagnosis for each dog, all the owners reported
      improvements in their dogs' behaviour after 12 weeks of treatment.

PMID- 16632529
TI  - Feline leukaemia virus (FeLV) and feline immunodeficiency virus infections in
      cats in the Pisa district of Tuscany, and attempts to control FeLV infection in a
      colony of domestic cats by vaccination.
AB  - The seroprevalence of feline immunodeficiency virus (FIV) in 203 apparently
      healthy domestic cats living in the district of Pisa, central Italy, was 11.3 per
      cent, and the prevalence of feline leukaemia virus (FeLV) was 8.4 per cent. The
      prevalence of FIV depended significantly on the lifestyle and age of the cats;
      cats living outdoors were more likely to be FIV-positive than cats living
      indoors, and the proportion of FIV-positive cats increased with age. In contrast,
      there was no significant relationship between these variables and the prevalence
      of FeLV. There was no significant relationship between the cats' seropositivity
      for FIV and FeLV. The results of a five-year field study to control FeLV
      infection by vaccination in a colony of 30 domestic adult cats naturally exposed
      to the infection suggest that the vaccination was effective in FIV-negative cats,
      but failed to protect FIV-positive cats against FeLV.

PMID- 16632530
TI  - Study of how frequently surgeons' gloves are perforated during operations.
AB  - Surgical gloves were collected after 231 first opinion and referral surgical
      procedures performed at the University of Liverpool Small Animal Hospital. They
      were tested for defects by the water load test and the site of any defects was
      recorded; 10.2 per cent of the gloves had defects, and at least one glove became
      defective during 51 (22.1 per cent) of the surgical procedures. Significantly
      more defects occurred during orthopaedic procedures and the likelihood of a
      defect occurring increased with the duration of the surgical procedure. The
      majority (78 per cent) of the defects occurred in the gloves worn on the non
      dominant hand and 64 per cent of them were in the index finger. The surgeon or
      assistant was aware of a glove being punctured in only 3.8 per cent of cases.

PMID- 16632531
TI  - Limited efficacy of an inactivated feline immunodeficiency virus vaccine.

PMID- 16632532
TI  - Risk factors for anaesthetic-related death in referred dogs.

PMID- 16632533
TI  - Ovarian teratoma in a bitch.

PMID- 16632534
TI  - Amoebic enterocolitis and acute myonecrosis in leopard tortoises (Geochelone
      pardalis).

PMID- 16632535
TI  - Eradication of FMD virus.

PMID- 16632536
TI  - Importation of gamebirds into the UK.

PMID- 16632537
TI  - Premovement testing for bovine TB.

PMID- 16632538
TI  - Investigating scent marking in dogs.

PMID- 16632539
TI  - Ivermectin resistance in Parascaris equorum.

PMID- 16632540
TI  - Maggots as a vector for avian influenza?

PMID- 16632541
TI  - Individual quarter agalactia in dairy cows.

PMID- 16632542
TI  - Mathematical modeling of gravitational effects on the circulation: importance of
      the time course of venous pooling and blood volume changes in the lungs.
AB  - A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing
      might be due to rapid pooling in the veins below the heart (preload) or muscle
      activation-induced drop in systemic vascular resistance (afterload). We
      hypothesized that, in the cardiovascular response to passive HUT, where, in
      contrast to active standing, little BP dip is observed, features affecting the
      preload play a key role. We developed a baroreflex model combined with a lumped
      parameter model of the circulation, including viscoelastic stress-relaxation of
      the systemic veins. Cardiac contraction is modeled using the varying-elastance
      concept. Gravity affects not only the systemic, but also the pulmonary,
      circulation. In accordance with the experimental results, model simulations do
      not show a BP dip on HUT; the tilt-back response is also realistic. If it is
      assumed that venous capacities are steady-state values, the introduction of
      stress-relaxation initially reduces venous pooling. The resulting time course of
      venous pooling is comparable to measured impedance changes. When venous pressure
      volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads
      to a drop in BP. The direct effect of gravity on the pulmonary circulation
      influences the BP response in the first approximately 5 s after HUT and tilt
      back. In conclusion, the initial BP response to HUT is mainly determined by the
      response of the venous system. The time course of lower body pooling is essential
      in understanding the response to passive HUT.

PMID- 16632543
TI  - COX-2 contributes to the maintenance of flow-induced dilation in arterioles of
      eNOS-knockout mice.
AB  - Our previous studies demonstrated that, in gracilis muscle arterioles of male
      mice deficient in the gene for endothelial nitric oxide synthase (eNOS), flow
      induced dilation (FID) is mediated by endothelial PGs. Thus the present study
      aimed to identify the specific isoform of cyclooxygenase (COX) responsible for
      the compensatory mediation of FID in arterioles of eNOS-knockout (KO) mice.
      Experiments were conducted on gracilis muscle arterioles of male eNOS-KO and wild
      type (WT) mice. Basal tone and magnitude of FID of arterioles were comparable in
      the two strains of mice. A role for COX isoforms in the mediation of the
      responses was assessed by use of valeryl salicylate (3 mM) and NS-398 (10
      microM), inhibitors of COX-1 and COX-2, respectively. In eNOS-KO arterioles,
      valeryl salicylate or NS-398 alone inhibited FID (at maximal flow rate) by
      approximately 51% and approximately 58%, respectively. Administration of both
      inhibitors eliminated the dilation. In WT arterioles, inhibition of COX-2 did not
      significantly affect FID, whereas inhibition of COX-1 decreased the dilation by
      approximately 57%. The residual portion of the response was abolished by
      additional administration of Nomega-nitro-L-arginine methyl ester. Western blot
      analysis indicated a comparable content of COX-1 protein in arterioles of WT and
      eNOS-KO mice. COX-2 protein, which was not detectable in arterioles of WT mice,
      was strongly expressed in arterioles of eNOS-KO mice, together with an
      upregulation of COX-2 gene expression. Immunohistochemical staining confirmed the
      presence of COX-2 in the endothelium of eNOS-KO arterioles. In conclusion, COX-2
      derived PGs are the mediators responsible for maintenance of FID in arterioles of
      eNOS-deficient mice.

PMID- 16632544
TI  - Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II
      induced cardiac hypertrophy.
AB  - Poly(ADP-ribose) polymerase-1 (PARP), a chromatin-bound enzyme, is activated by
      cell oxidative stress. Because oxidative stress is also considered a main
      component of angiotensin II-mediated cell signaling, it was postulated that PARP
      could be a downstream target of angiotensin II-induced signaling leading to
      cardiac hypertrophy. To determine a role of PARP in angiotensin II-induced
      hypertrophy, we infused angiotensin II into wild-type (PARP(+/+)) and PARP
      deficient mice. Angiotensin II infusion significantly increased heart weight-to
      tibia length ratio, myocyte cross-sectional area, and interstitial fibrosis in
      PARP(+/+) but not in PARP(-/-) mice. To confirm these results, we analyzed the
      effect of angiotensin II in primary cultures of cardiomyocytes. When compared
      with PARP(-/-) cardiomyocytes, angiotensin II (1 microM) treatment significantly
      increased protein synthesis in PARP(+/+) myocytes, as measured by (3)H-leucine
      incorporation into total cell protein. Angiotensin II-mediated hypertrophy of
      myocytes was accompanied with increased poly-ADP-ribosylation of nuclear proteins
      and depletion of cellular NAD content. When cells were treated with cell death
      inducing doses of angiotensin II (10-20 microM), robust myocyte cell death was
      observed in PARP(+/+) but not in PARP(-/-) myocytes. This type of cell death was
      blocked by repletion of cellular NAD levels as well as by activation of the
      longevity factor Sir2alpha deacetylase, indicating that PARP induction and
      subsequent depletion of NAD levels are the sequence of events causing angiotensin
      II-mediated cardiomyocyte cell death. In conclusion, these results demonstrate
      that PARP is a nuclear integrator of angiotensin II-mediated cell signaling
      contributing to cardiac hypertrophy and suggest that this could be a novel
      therapeutic target for the management of heart failure.

PMID- 16632545
TI  - Lifetimes of epicardial rotors in panoramic optical maps of fibrillating swine
      ventricles.
AB  - During ventricular fibrillation (VF), electrical activation waves are fragmented,
      and the heart cannot contract in synchrony. It has been proposed that VF waves
      emanate from stable periodic sources (often called "mother rotors"). The
      objective of the present study was to determine if stable rotors are consistently
      present on the epicardial surface of hearts comparable in size to human hearts.
      Using new optical mapping technology, we imaged VF from nearly the entire
      ventricular surface of six isolated swine hearts. Using newly developed pattern
      analysis algorithms, we identified and tracked VF wave fronts and phase
      singularities (PS; the pivot point of a reentrant wave front). We introduce the
      notion of a compound rotor in which the rotor's central PS can change and
      describe an algorithm for automatically identifying such patterns. This prevents
      rotor lifetimes from being inappropriately abbreviated by wave front
      fragmentation and collision events near the PS. We found that stable epicardial
      rotors were not consistently present during VF: only 1 of 17 VF episodes
      contained a compound rotor that lasted for the entire mapped interval of 4 s.
      However, shorter-lived rotors were common; 12.2 (SD 3.3) compound rotors with
      lifetime >200 ms were visible on the epicardium at any given instant. We conclude
      that epicardial mother rotors do not drive VF in this experimental model; if
      mother rotors do exist, they are intramural or septal. This paucity of persistent
      rotors suggests that individual rotors will eventually terminate by themselves
      and therefore that the continual formation of new rotors is critical for VF
      maintenance.

PMID- 16632546
TI  - Role of glutamate in a visceral sympathoexcitatory reflex in rostral
      ventrolateral medulla of cats.
AB  - The rostral ventrolateral medulla (rVLM) is involved in processing visceral
      sympathetic reflexes. However, there is little information on specific
      neurotransmitters in this brain stem region involved in this reflex. The present
      study investigated the importance of glutamate and glutamatergic receptors in the
      rVLM during gallbladder stimulation with bradykinin (BK), because glutamate is
      thought to function as an excitatory neurotransmitter in this region. Stimulation
      of visceral afferents activated glutamatergic neurons in the rVLM, as noted by
      double-labeling with c-Fos and the cellular vesicular glutamate transporter 3
      (VGLUT3). Visceral reflex activation significantly increased arterial blood
      pressure as well as extracellular glutamate concentrations in the rVLM as
      determined by microdialysis. Barodenervation did not alter the release of
      glutamate in the rVLM evoked by visceral reflex stimulation. Iontophoresis of
      glutamate into the rVLM enhanced the activity of sympathetic premotor
      cardiovascular rVLM neurons. Also, the responses of these neurons to visceral
      afferent stimulation with BK were attenuated significantly (70%) by blockade of
      glutamatergic receptors with kynurenic acid. Microinjection of either an N-methyl
      D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanate (25 mM, 30
      nl) or an dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (2 mM, 30 nl) into the rVLM
      significantly attenuated the visceral sympathoexcitatory reflex responses. These
      results suggest that glutamate in the rVLM serves as an excitatory
      neurotransmitter through a baroreflex-independent mechanism and that both NMDA
      and AMPA receptors mediate the visceral sympathoexcitatory reflex responses.

PMID- 16632547
TI  - Partial expression defect for the SCN5A missense mutation G1406R depends on
      splice variant background Q1077 and rescue by mexiletine.
AB  - Mutations in the cardiac Na(+) channel gene SCN5A cause loss of function and
      underlie arrhythmia syndromes. SCN5A in humans has two splice variants, one
      lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We
      investigated the effect of splice variant background on loss of function and
      rescue for G1406R, a mutation reported to cause Brugada syndrome. Mutant and wild
      type (WT) channels in both backgrounds were transfected into HEK-293 cells and
      incubated for up to 72 h with and without mexiletine. At 8 h, neither current nor
      cell surface expression was observed for the mutant in either background, but
      both were present in WT channels. At 24 h, small (<10% compared with WT) currents
      were noted and accompanied by cell surface expression. At 48 h, current density
      was approximately 40% of WT channels for the mutant in the Q1077del variant
      background but remained at <10% of WT channels in Q1077. Current levels were
      stable by 72 h. Coexpression with beta(1)- or beta(3)-subunits or insertion of
      the polymorphism H558R in the background did not significantly affect current
      expression. Mexiletine restored current density of the mutant channel in both
      backgrounds to nearly WT levels. The mutant channels also showed a negative shift
      in inactivation, slower recovery, and enhanced slow inactivation, consistent with
      a loss of function phenotype. These data show that a trafficking defect may be
      partial and time dependent and may differ with the splice variant background.
      Also, expression defects and gating abnormalities may contribute to loss of
      function for the same mutation.

PMID- 16632548
TI  - Transient permeabilization of cell membranes by ultrasound-exposed microbubbles
      is related to formation of hydrogen peroxide.
AB  - In the present study, we addressed the interactions among ultrasound,
      microbubbles, and living cells as well as consequent arising bioeffects. We
      specifically investigated whether hydrogen peroxide (H(2)O(2)) is involved in
      transient permeabilization of cell membranes in vitro after ultrasound exposure
      at low diagnostic power, in the presence of stable oscillating microbubbles, by
      measuring the generation of H(2)O(2) and Ca(2+) influx. Ultrasound, in the
      absence or presence of SonoVue microbubbles, was applied to H9c2 cells at 1.8 MHz
      with a mechanical index (MI) of 0.1 or 0.5 during 10 s. This was repeated every
      minute, for a total of five times. The production of H(2)O(2) was measured
      intracellularly with CM-H(2)DCFDA. Cell membrane permeability was assessed by
      measuring real-time changes in intracellular Ca(2+) concentration with fluo-4
      using live-cell fluorescence microscopy. Ultrasound, in the presence of
      microbubbles, caused a significant increase in intracellular H(2)O(2) at MI 0.1
      of 50% and MI 0.5 of 110% compared with control (P < 0.001). Furthermore, we
      found increases in intracellular Ca(2+) levels at both MI 0.1 and MI 0.5 in the
      presence of microbubbles, which was not detected in the absence of extracellular
      Ca(2+). In addition, in the presence of catalase, Ca(2+) influx immediately
      following ultrasound exposure was completely blocked at MI 0.1 (P < 0.01) and
      reduced by 50% at MI 0.5 (P < 0.001). Finally, cell viability was not
      significantly affected, not even 24 h later. These results implicate a role for
      H(2)O(2) in transient permeabilization of cell membranes induced by ultrasound
      exposed microbubbles.

PMID- 16632549
TI  - Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture).
AB  - Endothelial cells synthesize and release various factors that regulate
      angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and
      permeability. Endothelial dysfunction has been associated with a number of
      pathophysiological processes. Oxidative stress appears to be a common denominator
      underlying endothelial dysfunction in cardiovascular diseases. However, depending
      on the pathology, the vascular bed studied, the stimulant, and additional factors
      such as age, sex, salt intake, cholesterolemia, glycemia, and
      hyperhomocysteinemia, the mechanisms underlying the endothelial dysfunction can
      be markedly different. A reduced bioavailability of nitric oxide (NO), an
      alteration in the production of prostanoids, including prostacyclin, thromboxane
      A2, and/or isoprostanes, an impairment of endothelium-dependent
      hyperpolarization, as well as an increased release of endothelin-1, can
      individually or in association contribute to endothelial dysfunction. Therapeutic
      interventions do not necessarily restore a proper endothelial function and, when
      they do, may improve only part of these variables.

PMID- 16632550
TI  - Contribution of whole blood to the control of plasma asymmetrical
      dimethylarginine.
AB  - The endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetrical
      dimethylarginine (ADMA) is elevated in many patients and may contribute to the
      initiation and progression of their disease. While some mechanistic pathways have
      been identified, tissue-specific contributions to ADMA control remain unclear. We
      sought to determine if whole blood (WB) could participate in ADMA control ex
      vivo. Anesthetized male Sprague-Dawley rats underwent exsanguinations, and WB
      preparations were incubated at 37 degrees C for 5 h. ADMA and symmetrical
      dimethylarginine were analyzed by high-pressure liquid chromatography. Incubation
      of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA
      that was blocked by 4124W, a synthetic inhibitor of dimethylarginine
      dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA. Hydrolysis of
      ADMA was diminished by addition of physiologically relevant concentrations of
      zinc (i.e., 20 microM). Conversely, when rat WB or WB supernatant was incubated
      at 37 degrees C, it liberated quantities of free ADMA (1-2 microM) that in vivo
      would likely have pathological consequences. Addition of arginine
      methyltransferase inhibitors to these incubations did not reduce ADMA release,
      indicating no dominant role for active protein methylation during these
      incubations. This ADMA liberation was significantly reduced by addition of
      protease inhibitors, indicating a dependence on peptide bond hydrolysis. Total
      ADMA (protein incorporated plus free) was determined by acid hydrolysis and found
      to be 43.18 +/- 4.79 microM in WB with approximately 95% of this in RBCs. These
      ex vivo data demonstrate the potential of blood to control the NO-NOS system by
      modulating free ADMA.

PMID- 16632551
TI  - Blockade of NF-kappaB improves cardiac function and survival after myocardial
      infarction.
AB  - NF-kappaB is a key transcription factor that regulates inflammatory processes. In
      the present study, we tested the hypothesis that blockade of NF-kappaB
      ameliorates cardiac remodeling and failure after myocardial infarction (MI).
      Knockout mice with targeted disruption of the p50 subunit of NF-kappaB (KO) were
      used to block the activation of NF-kappaB. MI was induced by ligation of the left
      coronary artery in male KO and age-matched wild-type (WT) mice. NF-kappaB was
      activated in noninfarct as well as infarct myocardium in WT+MI mice, while the
      activity was completely abolished in KO mice. Blockade of NF-kappaB significantly
      reduced early ventricular rupture after MI and improved survival by ameliorating
      congestive heart failure. Echocardiographic and pressure measurements revealed
      that left ventricular fractional shortening and maximum rate of rise of left
      ventricular pressure were significantly increased and end-diastolic pressure was
      significantly decreased in KO+MI mice compared with WT+MI mice. Histological
      analysis demonstrated significant suppression of myocyte hypertrophy as well as
      interstitial fibrosis in the noninfarct myocardium of KO+MI mice. Blockade of NF
      kappaB did not ameliorate expression of proinflammatory cytokines in infarct or
      noninfarct myocardium. In contrast, phosphorylation of c-Jun NH2-terminal kinase
      was almost completely abolished in KO+MI mice. The present study demonstrates
      that targeted disruption of the p50 subunit of NF-kappaB reduces ventricular
      rupture as well as improves cardiac function and survival after MI. Blockade of
      NF-kappaB might be a new therapeutic strategy to attenuate cardiac remodeling and
      failure after MI.

PMID- 16632552
TI  - BDNF promotes connections of corticospinal neurons onto spared descending
      interneurons in spinal cord injured rats.
AB  - Although regeneration of injured axons is inhibited within the adult CNS,
      moderate recovery can be found in patients and animals with incomplete spinal
      cord injury (SCI). This can be partly attributed to sprouting of spared and
      injured axons, rostral and caudal to the lesion, respectively. Recently, it has
      been reported that following a thoracic SCI such sprouting can result in indirect
      reconnections of the lesioned axons to caudal targets via propriospinal
      interneurons (PrI). Here, we attempted to further promote this spontaneous repair
      mechanism by applying the neurotrophic factor BDNF (brain-derived neurotrophic
      factor), in the vicinity of the cell bodies of lesioned corticospinal neurons or
      NT-3, intrathecally to the cervical spinal cord. We performed a dorsal over
      hemisection at the thoracic spinal cord sparing only the left ventrolateral
      quadrant. This type of lesion did not promote sprouting of injured corticospinal
      axons or re-routing via commissural PrI. Also, in rats that received NT-3 at the
      cervical enlargement, no increase in sprouting was found. However, animals
      receiving BDNF at the cell bodies of lesioned corticospinal neurons showed a
      significant increase in collateral sprouting and in the number of contacts with
      PrI. This was not observed when BDNF was administered to unlesioned animals.
      Although no statistical difference in the horizontal ladder walking was found
      between the groups, the increase in collateral sprouting and in the number of
      contacts correlated with the functional recovery. Hence, cell body treatment can
      promote plasticity of the injured CNS and may be a valuable treatment approach in
      conjunction with local regeneration promoting strategies.

PMID- 16632553
TI  - High-frequency oscillations during human focal seizures.
AB  - Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have
      previously been recorded in human epileptic brains using depth microelectrodes.
      We describe for the first time similar oscillations in a cohort of unselected
      focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis
      and visual inspection techniques were used to study seizures from 10 consecutive
      patients undergoing pre-surgical evaluation for medically refractory focal
      epilepsy. Four of these patients had focal seizure onset in the mesial temporal
      lobe, and in all 12 of their seizures, well-localized, segmental, very high
      frequency band (VHF: 250-500 Hz) oscillations were visually identified near the
      time of seizure onset from contacts in this zone. Increased high-frequency band
      (HF: 100-200 Hz) activity compared with the background was distinguished both
      visually and with spectral analysis later in the seizures of 3/4 mesial temporal
      patients, involving contacts in the generator region and, in one patient, areas
      of contralateral peri-hippocampal propagation. Three patients with well-defined
      neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations
      confined to the seizure-onset channels during their eight seizures. No discrete
      HF or VHF activity was present in the poorly localized seizures from the
      remaining three patients. These results show that discrete HFOs can be recorded
      from human focal epileptic brain using depth macroelectrodes, and that they occur
      mostly in regions of primary epileptogenesis and rarely in regions of secondary
      spread. Absent high-frequency activity seems to indicate poor localization,
      whereas the presence of focal HFOs near the time of seizure onset may signify
      proximity to the epileptogenic focus in mesial temporal lobe and neocortical
      seizures. We postulate that focal HFOs recorded with depth macroelectrodes
      reflect the partial synchronization of very local oscillations such as those
      previously studied using microelectrodes, and result from interconnected small
      neuronal ensembles. Our finding that localized HFOs occur in varying anatomical
      structures and pathological conditions perhaps indicates commonality to diverse
      epileptogenic aetiologies.

PMID- 16632554
TI  - Understanding pathogenesis and therapy of multiple sclerosis via animal models:
      70 years of merits and culprits in experimental autoimmune encephalomyelitis
      research.
AB  - In view of disease heterogeneity of multiple sclerosis and limited access to ex
      vivo specimens, different approaches must be undertaken to better understand
      disease pathogenesis and new therapeutic challenges. Here, we critically discuss
      models of experimental autoimmune encephalomyelitis (EAE) that reproduce specific
      features of the histopathology and neurobiology of multiple sclerosis and their
      shortcomings as tools to investigate emerging therapeutic approaches. By using
      EAE models we have understood mechanisms of T-cell mediated immune damage of the
      CNS, and the associated effector cascade of innate immunity. Also, the importance
      of humoral components of the immune system for demyelination has been delineated
      in EAE, before it was applied therapeutically to subtypes of multiple sclerosis.
      Yet, similar to multiple sclerosis, EAE is also heterogeneous and influenced by
      the selected autoantigen, species and the genetic background. In particular, the
      relevance of cytotoxic CD8 T cells for human multiple sclerosis has been
      underestimated in most EAE models, and no EAE model exists that mimics primary
      progressive disease courses of multiple sclerosis. Seventy years after the first
      description of EAE and the publication of >7000 articles, we are aware of the
      obvious limitations of EAE as a model of multiple sclerosis, but feel strongly
      that when used appropriately it will continue to provide a crucial tool for
      improving our understanding and treatment of this devastating disease.

PMID- 16632555
TI  - Re: "Associations between breast cancer risk and the catalase genotype, fruit and
      vegetable consumption, and supplement use".

PMID- 16632556
TI  - Hypercholesterolaemia is not associated with early atherosclerotic lesions in
      primary biliary cirrhosis.
AB  - BACKGROUND: Hypercholesterolaemia often occurs in primary biliary cirrhosis (PBC)
      as a result of chronic cholestasis, but whether these patients are exposed to
      greater cardiovascular risk is unknown. AIM: To establish whether
      hypercholesterolaemia is associated with subclinical atherosclerosis in PBC.
      PATIENTS: 103 consecutive patients with PBC (37 with total cholesterol > or =6.21
      mmol/l) and 37 controls with hypercholesterolaemia, and 141 matched controls with
      normocholesterolaemia. METHODS: Ultrasound imaging of carotid artery to determine
      intima-media thickness (IMT) and stenosis. RESULTS: Controls with
      hypercholesterolaemia had higher IMT and prevalence of carotid stenosis compared
      with patients with hypercholesterolaemic PBC (mean (SD) 0.850 (0.292) mm v 0.616
      (0.137) mm, p(c)<0.001; 43% v 19%, p(c) = 0.129) who, in turn, were similar to
      the 66 patients with normocholesterolaemic PBC (0.600 (0.136) mm; 5%). Compared
      with subjects with normocholesterolaemia, controls with hypercholesterolaemia,
      but not patients with hypercholesterolaemic PBC, had an increased risk of raised
      IMT (odds ratio (OR) 5.4, 95% confidence interval (CI) 2.5 to 11.9, p<0.001; and
      0.7, 0.3 to 2.0, p = 0.543) or carotid stenosis (8.2, 3.4 to 20, p<0.001; and
      2.5, 0.9 to 6.9, p = 0.075). In PBC, compared with younger patients without
      hypertension, the risk of increased IMT was OR (CI) 3.1 (0.6 to 17; p = 0.192) in
      patients with hypertension or old age, but not hypercholesterolaemia, and 4.6
      (0.8 to 27; p = 0.096) in patients who also had hypercholesterolaemia. The
      corresponding figures for risk of stenosis were 3.6 (0.4 to 36; p = 0.277) and
      15.8 (1.8 to 141; p = 0.014). CONCLUSIONS: Hypercholesterolaemia is not
      consistently associated with subclinical atherosclerosis in PBC, but should be
      treated if other risk factors for cardiovascular disease are also present. The
      search for factors that may protect patients with hypercholesterolaemic PBC
      against atherosclerosis should be encouraged.

PMID- 16632557
TI  - High-efficiency short daily haemodialysis--morbidity and mortality rate in a long
      term study.
AB  - BACKGROUND: In conventional haemodialysis (CHD), the morbidity and mortality rate
      is unacceptably high; consequently, variations in the length and frequency of the
      haemodialysis sessions have been studied to reduce the complications of dialysis
      treatment. In this sense, high-efficiency short daily haemodialysis (SDHD) has
      been proposed as an alternative for patients on renal replacement therapy. In
      this study, we have related our experience with this dialysis modality. METHODS:
      Twenty-six patients (16 males, mean age 35.6 +/- 14.7 years) were treated by SDHD
      for 33.6 +/- 18.5 months (range 6-57 months). The mean time on CHD before the
      switch to SDHD was 25.5 +/- 31.9 months (range 1-159 months). In 23 (88.5%)
      patients, native arteriovenous fistulae were used for vascular access. SDHD was
      performed six times a week, 1.5-2 h per session, and high flux polysulfone
      dialysers (surface area: 1.8 m(2)) were employed. The blood flow and dialysate
      flow rate were 350 and 800 ml/min, respectively. RESULTS: In this trial, the
      patient survival was 100%. The vascular access survival after 12, 24, 36 and 48
      months on SDHD was 100, 89, 89 and 80%, respectively. There were three failures
      of vascular access in 72.7 patient-years (0.04 failures/patient-year). In 15
      patients on SDHD during 36 consecutive months, the vascular access survival after
      12, 24, 36 and 48 months was 100, 93, 93 and 84%, respectively. Also, in this
      group of patients, there were 0.27 hospitalizations/patient-year and 1.24 days of
      hospitalizations/patient-year. CONCLUSIONS: We concluded that in a long-time
      study of patients on SDHD the morbidity and mortality rate is very low.
      Furthermore, we observed that failures of vascular access are not a significant
      problem. Consequently, we believe that SDHD is a powerful renal replacement
      therapy for treatment of patients on maintenance haemodialysis.

PMID- 16632558
TI  - Bovine ureter graft for haemodialysis access surgery.

PMID- 16632559
TI  - Kidney biopsy in lupus nephritis: look before you leap.

PMID- 16632560
TI  - Six cases of retained central venous haemodialysis access catheters.

PMID- 16632561
TI  - Carbohydrate intake and tennis: are there benefits?
AB  - Carbohydrate supplementation in prolonged aerobic exercise has been shown to be
      effective in improving performance and deferring fatigue. However, there is
      confounding evidence with regard to carbohydrate supplementation and tennis
      performance, which may be due to the limited number of studies on this topic.
      This evidence based review, using database searches of Medline and SPORTDiscus,
      summarises the limited relevant literature to determine if carbohydrate
      supplementation benefits tennis performance, and, if so, the appropriate amounts
      and timing. Although more research is required, it appears that it may be
      beneficial in tennis sessions lasting more than 90 minutes.

PMID- 16632562
TI  - How should we teach sports medicine?

PMID- 16632563
TI  - Fuzzy balls.

PMID- 16632564
TI  - Medical care of tennis players by country.

PMID- 16632565
TI  - Applied physiology of tennis performance.
AB  - Competitive tennis play requires a combination of the major physiological
      variables; however, the specifics of these variables have yet to be determined
      appropriately. General strength and flexibility training have been suggested as
      being beneficial for performance and injury prevention, yet specific guidelines
      are lacking. This paper provides a review of specific studies that relate to
      competitive tennis, and highlights the need for tennis-specific training as
      opposed to generalised physical training. It identifies specific studies that
      support the premise that tennis has physiological requirements which need to be
      understood when designing training and research programmes.

PMID- 16632566
TI  - Intensity of tennis match play.
AB  - This review focuses on the characteristics of tennis players during match play
      and provides a greater insight into the energy demands of tennis. A tennis match
      often lasts longer than an hour and in some cases more than five hours. During a
      match there is a combination of periods of maximal or near maximal work and
      longer periods of moderate and low intensity activity. Match intensity varies
      considerably depending on the players' level, style, and sex. It is also
      influenced by factors such as court surface and ball type. This has important
      implications for the training of tennis players, which should resemble match
      intensity and include interval training with appropriate work to rest ratios.

PMID- 16632567
TI  - Biomechanics and tennis.
AB  - Success in tennis requires a mix of player talent, good coaching, appropriate
      equipment, and an understanding of those aspects of sport science pertinent to
      the game. This paper outlines the role that biomechanics plays in player
      development from sport science and sport medicine perspectives. Biomechanics is a
      key area in player development because all strokes have a fundamental mechanical
      structure and sports injuries primarily have a mechanical cause.

PMID- 16632568
TI  - Unforced errors and error reduction in tennis.
AB  - Only at the highest level of tennis is the number of winners comparable to the
      number of unforced errors. As the average player loses many more points due to
      unforced errors than due to winners by an opponent, if the rate of unforced
      errors can be reduced, it should lead to an increase in points won. This article
      shows how players can improve their game by understanding and applying the laws
      of physics to reduce the number of unforced errors.

PMID- 16632569
TI  - Modern tennis rackets, balls, and surfaces.
AB  - Modern rackets have facilitated a change in playing style from one of technique
      to one characterised by power and spin. The combination of the increased
      stiffness of modern rackets and the tendency for tennis balls to have become
      harder has led to an increased shock transmission from the racket to the player,
      which is probably a major contributor to tennis elbow. The paucity of tennis
      specific research on shoes and surfaces makes it difficult to link their
      characteristics with lower limb injury, although, as their interaction directly
      affects the magnitude of the forces to which the player is exposed, such a link
      seems reasonable.

PMID- 16632570
TI  - Voluntary fluid intake and core temperature responses in adolescent tennis
      players: sports beverage versus water.
AB  - OBJECTIVE: To examine differences in ad libitum fluid intake, comparing a 6%
      carbohydrate/electrolyte drink (CHO-E) and water, and associated differences in
      core temperature and other selected physiological and perceptual responses in
      adolescent athletes during tennis training in the heat. METHODS: Fourteen
      healthy, fit, young tennis players (nine male; five female; mean (SD) age 15.1
      (1.4) years; weight 60.6 (8.3) kg; height 172.8 (8.6) cm) completed two 120
      minute tennis specific training sessions on separate days (randomised, crossover
      design) in a warm environment (wet bulb globe temperature: CHO-E, 79.3 (2.6)
      degrees F; water, 79.9 (2.2) degrees F; p>0.05). RESULTS: There were no
      significant differences (p>0.05) between the trials with respect to fluid intake,
      urine volume, fluid retention, sweat loss, perceived exertion, thirst, or
      gastrointestinal discomfort. However, there was a difference (p<0.05) in the
      percentage body weight change after training (CHO-E, -0.5 (0.7)%; water, -0.9
      (0.6)%). Urine specific gravity before training (CHO-E, 1.024 (0.006); water,
      1.025 (0.005)) did not correlate significantly (p>0.05) with any of these
      measurements or with core body temperature. In examining the main effect for
      trial, the CHO-E trial showed a significantly lower (p<0.001) mean body
      temperature (irrespective of measurement time) than the water trial. However, the
      mean body temperature in each trial was not associated (p>0.05) with fluid
      intake, fluid retention, sweat loss, or percentage body weight change.
      CONCLUSION: Ad libitum consumption of a CHO-E drink may be more effective than
      water in minimising fluid deficits and mean core temperature responses during
      tennis and other similar training in adolescent athletes.

PMID- 16632571
TI  - Isokinetic profile of wrist and forearm strength in elite female junior tennis
      players.
AB  - BACKGROUND: In tennis, injuries to the elbow and wrist occur secondary to the
      repetitive nature of play and are seen at increasingly young ages. Isokinetic
      testing can be used to determine muscular strength levels, but dominant/non
      dominant and agonist/antagonist relations are needed for meaningful
      interpretation of the results. OBJECTIVES: To determine whether there are
      laterality differences in wrist extension/flexion (E/F) and forearm
      supination/pronation (S/P) strength in elite female tennis players. METHODS: 32
      elite female tennis players (age 12 to 16 years) with no history of upper
      extremity injury underwent bilateral isokinetic testing using a Cybex 6000
      dynamometer. Peak torque and single repetition work values for wrist E/F and
      forearm S/P were measured at speeds of 90 degrees/s and 210 degrees/s, with
      random determination of the starting extremity. Repeated measures analysis of
      variance was used to determine differences between extremities for peak torque
      and single repetition work values. RESULTS: Significantly greater (p<0.01)
      dominant arm wrist E/F and forearm pronation strength was measured at both
      testing speeds. Significantly less (p<0.01) dominant side forearm supination
      strength was measured at both testing speeds. CONCLUSIONS: Greater dominant arm
      wrist E/F and forearm pronation strength is common and normal in young elite
      level female tennis players. These strength relations indicate sport specific
      muscular adaptations in the dominant tennis playing extremity. The results of
      this study can guide clinicians who work with young athletes from this
      population. Restoring greater dominant side wrist and forearm strength is
      indicated after an injury to the dominant upper extremity in such players.

PMID- 16632573
TI  - Extensor carpi ulnaris injuries in tennis players: a study of 28 cases.
AB  - Pain on the ulnar side of the wrist is common among elite tennis players. Ten
      years of experience has allowed identification of a pathology involving the
      extensor carpi ulnaris (ECU) tendon. On the basis of 28 clinical cases seen over
      the last five years, three clinical patterns are described: (a) acute instability
      of the ECU; (b) tendinopathy; (c) ECU rupture. Each of these clinical entities
      requires a different therapeutic approach. A review of the relevant anatomy is
      provided.

PMID- 16632572
TI  - Tennis injuries: occurrence, aetiology, and prevention.
AB  - A systematic search of published reports was carried out in three electronic
      databases from 1966 on to identify relevant articles relating to tennis injuries.
      There were 39 case reports, 49 laboratory studies, 28 descriptive epidemiological
      studies, and three analytical epidemiological studies. The principal findings of
      the review were: first, there is a great variation in the reported incidence of
      tennis injuries; second, most injuries occur in the lower extremities, followed
      by the upper extremities and then the trunk; third, there have been very few
      longitudinal cohort studies that investigated the association between risk
      factors and the occurrence of tennis injuries (odds ratios, risk ratios, hazard
      ratios); and fourth, there were no randomised controlled trials investigating
      injury prevention measures in tennis. More methodologically sound studies are
      needed for a better understanding of risk factors, in order to design useful
      strategies to prevent tennis injuries.

PMID- 16632574
TI  - Postero-medial elbow problems in the adult athlete.
AB  - The ligamentous, osseous, musculotendinous, and neural structures at the postero
      medial side of the elbow are at risk for various injuries in overhead athletes.
      The combination of valgus and extension overload during overhead activities
      results in tensile forces along the medial stabilising structures, with
      compression on the lateral compartment and shear stress posteriorly. The
      combination of tensile forces medially and shear forces posteriorly can result in
      ulnar collateral ligament (UCL) tears, flexor-pronator mass injuries, neuritis of
      the ulnar nerve, posterior impingement, and olecranon stress fractures. Most
      symptomatic conditions of the overhead athlete can be treated conservatively
      initially. In cases where conservative treatment is unsuccessful surgical
      intervention is indicated. Recent advances in arthroscopic surgical techniques
      and ligamentous reconstruction ensure that the prognosis for return to pre-injury
      level is good.

PMID- 16632575
TI  - Shoulder injuries in tennis players.
AB  - The mechanism of the overhead action in throwing sports has been studied
      extensively. This motion is unnatural and highly dynamic, often exceeding the
      physiological limits of the joint. Owing to overload of various anatomical
      structures, the shoulder is susceptible to injury. Optimal shoulder function
      requires good kinetic chain function, optimal stability, and coordination of the
      scapula in the overhead action. A well balanced action of the rotator cuff
      muscles and capsular structures is necessary to obtain a stable centre of
      rotation during the overhead action. This review concerns shoulder injuries,
      related to the overhead motion in tennis players, which can be explained by the
      same mechanism as thrower's shoulder.

PMID- 16632577
TI  - Is tennis a predisposing factor for degenerative shoulder disease? A controlled
      study in former elite players.
AB  - BACKGROUND: High demands imposed to the shoulder during tennis activity can
      decrease the efficiency of static and dynamic constraints. Subtle or frank
      instability of the glenohumeral joint may occur, and long term degenerative
      changes may be expected. OBJECTIVE: To determine and compare the prevalence of
      primary glenohumeral osteoarthritis in senior tennis players and matched
      controls. STUDY DESIGN: Cross sectional controlled study. METHODS: 18
      asymptomatic senior tennis players were studied (17 male; mean (SD) age, 57.2
      (8.8) years) with no history of shoulder surgery or major trauma. There were 18
      matched controls. Radiographs were used to determine glenohumeral osteoarthritic
      changes: joint space narrowing, humeral and glenoid subchondral sclerosis,
      humeral and glenoid juxta-articular cysts, osteophytes, humeral and glenoid
      flattening, humeral posterior displacement and glenoid posterior erosion.
      Findings were classified as normal, minimal, moderate, or severe changes.
      RESULTS: 33% of the players (95% confidence interval (CI), 13% to 59%) had
      osteoarthritic changes in their dominant shoulder (n = 6; five with minimal
      changes, one with moderate changes), and 11% of the controls (95% CI, 1% to 34%)
      had articular degeneration on their dominant side (n = 2; both minimal changes)
      (p = 0.04, Wilcoxon test). The osteoarthritic group was significantly older than
      the players without degenerative changes (p = 0.008). CONCLUSIONS: The prevalence
      of glenohumeral osteoarthritis in the dominant shoulder was greater in former
      elite tennis players than in sedentary controls. Prolonged intensive tennis
      practice may be a predisposing factor for the development of mild degenerative
      articular changes in the dominant shoulder.

PMID- 16632576
TI  - Spondylolysis in young tennis players.
AB  - The general aetiology, diagnosis, and treatment of spondylolysis, a bone defect
      in the pars interarticularis of the vertebra, are reviewed. A retrospective study
      of young tennis players diagnosed between 2000 and 2004 with spondylolysis with
      or without spondylolisthesis, assessed by radiography and planar bone
      scintigraphy, is described. If the radiographic results were negative, computed
      tomography was performed. Sixty six cases were evaluated: 53 L5 lesions, eight L4
      lesions, two L3 lesions, and one bilateral lesion at the L2 level. Two more
      lesions at two levels were found (bilateral L5 and unilateral L4 and L3 on the
      right side). Classification, treatment, and outcome of the cases are reported. A
      combination of radiography, planar bone scintigraphy, and SPECT is useful for
      evaluating spondylolysis in tennis players and recommending treatment. Use of a
      brace did not appear to achieve significant results.

PMID- 16632578
TI  - Tennis specific limitations in players with an ACL deficient knee.
AB  - BACKGROUND: Complete rupture of the anterior cruciate ligament (ACL) causes
      significant alteration of knee joint kinematics. Untreated patients often develop
      joint instability, chronic articular degeneration, and knee dysfunction. Demands
      on the ACL produced by playing tennis have not been investigated. OBJECTIVE: To
      identify subjective sport-specific limitations in tennis players with isolated
      unilateral ACL deficiency. STUDY DESIGN: Prospective case-control study. METHODS:
      16 players (mean (SD) age, 39.9 (2.3) years; 14 men) with a chronic unilateral
      ACL deficient knee and 16 healthy controls (38.25 (8.47) years; 14 men) were
      recruited. ACL deficiency was confirmed by clinical and magnetic resonance
      imaging. A Lysholm score was obtained in all patients, together with subjective
      evaluation of their current tennis performance compared with pre-injury levels,
      applying a 0-100% visual scale. Both groups completed a questionnaire on tennis
      specific abilities. RESULTS: Lysholm scores were: 85.6 (10.3) points in the study
      group and 100 (0) points in the control group (p<0.001, t test for independent
      samples). Injured players evaluated their current tennis performance as 66.8
      (15.2)% compared with 100% pre-injury level (p<0.005, t test for dependent
      samples). Abilities affected in the ACL deficient group were landing after a
      smash stroke (p<0.001); stopping abruptly and changing (p<0.001); playing a three
      set singles match (p<0.05); and playing on a hard court surface (p<0.001,
      Kolmogorov-Smirnov test). CONCLUSIONS: There are specific limitations associated
      with complete isolated ACL rupture, including subjective tennis performance
      impairment, limitations landing after a smash, stopping and changing step
      direction, difficulties playing a three set singles match, and playing on hard
      court surfaces.

PMID- 16632579
TI  - The incidence and distribution of stress fractures in elite tennis players.
AB  - BACKGROUND: Modern professional tennis involves powerful movements repeatedly
      subjecting the musculoskeletal system to heavy mechanical load. Thus tennis
      players are exposed to high risk of overuse injuries including stress fractures.
      OBJECTIVE: To determine the incidence and distribution of stress fractures in
      elite tennis players. STUDY DESIGN: Retrospective cohort study. METHODS: The
      cohort study population consisted of 139 elite players (mean (SD) age, 20.0 (5.0)
      years; 48 female, 91 male). Stress fractures were identified and confirmed
      radiologically from medical records during a two year period. Injuries were
      analysed according to age, sex, site, severity, delay in diagnosis, and time
      needed to return to sports. RESULTS: 15 players sustained 18 stress fractures,
      corresponding to an overall case incidence of 12.9% (95% confidence interval
      (CI), 8.1 to 20.0). The tarsal navicular was most affected (n = 5; 27%), followed
      by the pars interarticularis (n = 3; 16%), the metatarsals (n = 3; 16%), the
      tibia (n = 2; 11%) and the lunate (n = 2; 11%). Magnetic resonance imaging showed
      a greater incidence of "high grade" lesions (94.4%). Stress fracture incidence
      was significantly higher in juniors (20.3% (95% CI, 11.4 to 33.2)) than in
      professional players (7.5% (2.8 to 15.6)) (p = 0.045). CONCLUSIONS: There was a
      high absolute risk (12.9%) of stress fractures in elite tennis players over a two
      year period. Junior players were at highest risk. The lesions are a major cause
      of disruption both of training and of competition. Risk factors should therefore
      be identified and prevention emphasised.

PMID- 16632580
TI  - Sacral stress fracture: an unusual cause of low back pain in an amateur tennis
      player.
AB  - Stress fractures are common in athletes, and their incidence in sport is
      estimated at 2-4%. A case is reported of a stress fracture of the sacrum in an
      amateur tennis player. The patient was treated with rest and physiotherapy,
      focusing on stretching programmes and analgesic treatments, followed by an
      educational programme of tennis training and muscle strengthening. This appears
      to be the first report of this pathology in a tennis player.

PMID- 16632581
TI  - Uncommon abdominal muscle injury in a tennis player: internal oblique strain.
AB  - The case of a strain injury of the internal oblique abdominal muscle in a
      professional tennis player is presented. This uncommon lesion resulted from
      eccentric, unbalanced trunk rotation. Magnetic resonance imaging helped to
      confirm the diagnosis. Tennis specific core strengthening is crucial for
      rehabilitation and recurrence prevention.

PMID- 16632582
TI  - The Sony Ericsson WTA Tour 10 year age eligibility and professional development
      review.
AB  - Concerns have long existed over the participation of adolescent athletes in
      professional sports. In 2004, the Sony Ericsson WTA Tour (WTA Tour) commissioned
      a Professional Development Advisory Panel (PDAP) to evaluate the WTA Tour's age
      eligibility rule (AER) and professional development programmes (PDPs) for female
      tennis players since their inception in 1995. More than 75% of the 628
      respondents supported the principles of the AER, and 90% indicated a need for
      PDPs. Statistical analysis of WTA Tour players' careers found that premature
      retirements (players leaving the Tour at or before age 21) decreased
      significantly from 7% before the AER to less than 1% afterward, and median career
      length increased by 43%. The PDAP recommends that the WTA Tour continues a phased
      in, developmentally appropriate AER, enhances the PDPs, and works with other
      sport governing bodies to coordinate rules and programmes at earlier ages to aid
      the transition of adolescents into adult sports.

PMID- 16632583
TI  - Health benefits for veteran (senior) tennis players.
AB  - To explore the health benefits of tennis participation in veteran players and to
      identify future research needs, an electronic literature search using the Ovid
      (Cinhal, Medline, Sport Discus) library databases from 1966-2005 was undertaken.
      Specific search words were employed related to tennis, aging, exercise, health,
      and the psychophysiological systems. Public access internet search engines were
      also used (Google, PubMed), along with non-electronic searches of library
      holdings. There is ample research documenting the health benefits of regular
      participation in moderately intense aerobic activity. There have been research
      studies targeting veteran tennis players but most were cross sectional. No tennis
      related study successfully eliminated all confounding cross training effects. The
      health of veteran tennis players is improved by enhanced aerobic capacity,
      greater bone densities in specific regions, lower body fat, greater strength, and
      maintained reaction time performance in comparison with age matched but less
      active controls. However, it is not certain whether tennis alone can be a sole
      contributor to these physiological variables. Well controlled longitudinal
      research among elite veteran and novice older adult players is needed.

PMID- 16632584
TI  - Leaving the professional tennis circuit: exploratory study of experiences and
      reactions from elite female athletes.
AB  - In 2002, Tennis Australia commissioned a report into the experiences of elite
      female past players on leaving the professional tennis circuit. Australian
      players who were in the top 800 of the Women's Tennis Association (WTA) end of
      year rankings and who had left the professional circuit within the previous 15
      years were asked by mail to respond to a questionnaire. The questionnaire asked
      players to describe their feelings about leaving the tour during the time leading
      up to leaving the tour to two years after retirement. The main findings of the
      study suggested that those who planned to leave the tour found the transition
      process easy, whereas those who did not plan to leave the tour found the process
      difficult. Most players (66%) did not regret leaving the tour, and, although the
      remaining players responded that they regretted leaving, none attempted a
      comeback. Tennis Australia has implemented strategies to assist current players
      on the professional tour based on the results of this study.

PMID- 16632585
TI  - Development of a Korean adult male computational phantom for internal dosimetry
      calculation.
AB  - A Korean adult male computational phantom was constructed based on the current
      anthropometric and organ volume data of Korean average adult male, and was
      applied to calculate internal photon dosimetry data. The stylised models of
      external body, skeleton, and a total of 13 internal organs (brain, gall bladder,
      heart, kidneys, liver, lungs, pancreas, spleen, stomach, testes, thymus, thyroid
      and urinary bladder) were redesigned based on the Oak Ridge National Laboratory
      (ORNL) adult phantom. The height of trunk of the Korean phantom was 8.6% less
      than that of the ORNL adult phantom, and the volumes of all organs decreased up
      to 65% (pancreas) except for brain, gall bladder wall and thymus. Specific
      absorbed fraction (SAF) was calculated using the Korean phantom and Monte Carlo
      code, and compared with those from the ORNL adult phantom. The SAF of organs in
      the Korean phantom was overall higher than that from the ORNL adult phantom. This
      was caused by the smaller organ volume and the shorter inter-organ distance in
      the Korean phantom. The self SAF was dominantly affected by the difference in
      organ volume, and the SAF for different source and target organs was more
      affected by the inter-organ distance than by the organ volume difference. The
      SAFs of the Korean stylised phantom differ from those of the ORNL phantom by 10
      180%. The comparison study of internal dosimetry will be extended to tomographic
      phantom and electron source in the future.

PMID- 16632586
TI  - In situ gamma-ray spectrometry for environmental monitoring: a semi empirical
      calibration method.
AB  - In situ gamma spectrometry using high-purity germanium (HPGe) detectors is a
      frequently used method for the determination of radionuclide ground deposition
      levels. Such measurements do, however, require an efficiency calibration based on
      detector sensitivity and parameters such as soil density and vertical activity
      distribution. In this work, a novel expression is used for the detector
      efficiency, incorporating both the influence of photon energy and incidence
      angle. Detector-specific efficiency data are determined empirically. For the
      theoretical calculation of the photon fluence at the detector, a three-layer
      model of finite thickness is developed for the description of soil density and
      vertical activity distribution. In order to facilitate the calibration of in situ
      measurements, a PC program has been developed to enable rapid, on-site
      calculations of radionuclide ground deposition levels. The semi empirical
      calibration method was tested on in situ measurements with two different
      detectors, and the results show good agreement with results obtained from
      traditional soil sampling.

PMID- 16632587
TI  - Glycinebetaine counteracts the inhibitory effects of salt stress on the
      degradation and synthesis of D1 protein during photoinhibition in Synechococcus
      sp. PCC 7942.
AB  - Glycinebetaine (hereafter referred to as betaine) is a compatible solute that
      accumulates in certain plants and microorganisms in response to various types of
      stress. We demonstrated previously that when the cyanobacterium Synechococcus sp.
      PCC 7942 (hereafter Synechococcus) is transformed with the codA gene for choline
      oxidase, it can synthesize betaine from exogenously supplied choline, exhibiting
      enhanced tolerance to salt and cold stress. In this study, we examined the
      effects of salt stress and betaine synthesis on the photoinhibition of
      photosystem II (PSII). Salt stress due to 220 mm NaCl enhanced photoinhibition of
      PSII and betaine protected PSII against photoinhibition under these conditions.
      However, neither salt stress nor betaine synthesis affected photodamage to PSII.
      By contrast, salt stress inhibited repair of photodamaged PSII and betaine
      reversed this inhibitory effect of salt stress. Pulse-chase-labeling experiments
      revealed that salt stress inhibited degradation of D1 protein in photodamaged
      PSII and de novo synthesis of D1. By contrast, betaine protected the machinery
      required for degradation and synthesis of D1 under salt stress. Neither salt
      stress nor betaine affected levels of psbA transcripts. These observations
      suggest that betaine counteracts the inhibitory effects of salt stress, with
      resultant accelerated repair of photodamaged PSII.

PMID- 16632588
TI  - Inhibition of brassinosteroid biosynthesis by either a dwarf4 mutation or a
      brassinosteroid biosynthesis inhibitor rescues defects in tropic responses of
      hypocotyls in the arabidopsis mutant nonphototropic hypocotyl 4.
AB  - The nonphototropic hypocotyl 4 (nph4)/auxin response factor 7 (arf7) mutant of
      Arabidopsis (Arabidopsis thaliana) is insensitive to auxin and has defects in
      hypocotyl tropism, hook formation, differential leaf growth, and lateral root
      formation. To understand an auxin-signaling pathway through NPH4, we carried out
      screening of suppressor mutants of nph4-103 and obtained a dwarf suppressor
      mutant, suppressor of nph4 (snp2). snp2 had short hypocotyls in the dark
      condition and dark green and round leaves, short petioles, and more lateral
      shoots than the wild type in the light condition. The snp2 phenotypes were
      rescued by adding brassinolide to the growth medium in both light and dark
      conditions. Genetic mapping, sequence analysis, and a complementation test
      indicated that snp2 was a weak allele of DWARF4 (DWF4), which functions in
      brassinosteroid (BR) biosynthesis. snp2, which was renamed dwf4-101, exhibited
      photo- and gravitropisms of hypocotyls similar to those of the wild type with a
      slightly faster response in gravitropism. dwf4-101 almost completely suppressed
      defects in both tropisms of nph4-103 hypocotyls and completely suppressed
      hyponastic growth of nph4-103 leaves. Treatment with brassinazole, an inhibitor
      of BR biosynthesis, also partially rescued the tropic defects in nph4-103.
      Hypocotyls of nph4-103 were auxin insensitive, whereas hypocotyls of dwf4-101
      were more sensitive than those of the wild type. dwf4-101 nph4-103 hypocotyls
      were as sensitive as those of dwf4-101. Auxin inducibility of massugu 2
      (MSG2)/IAA19 gene expression was reduced in nph4-103. mRNA level of MSG2 was
      reduced in dwf4-101 and dwf4-101 nph4-103, but both mutants exhibited greater
      auxin inducibility of MSG2 than the wild type. Taken together, dwf4-101 was
      epistatic to nph4-103. These results strongly suggest that BR deficiency
      suppresses nph4-103 defects in tropic responses of hypocotyls and differential
      growth of leaves and that BR negatively regulates tropic responses.

PMID- 16632589
TI  - Evidence for K+-dependent HCO3- utilization in the marine diatom Phaeodactylum
      tricornutum.
AB  - Photosynthetic utilization of inorganic carbon in the marine diatom Phaeodactylum
      tricornutum was investigated by the pH drift experiment, measurement of K(1/2)
      values of dissolved inorganic carbon (DIC) with pH change, and comparison of the
      rate of photosynthesis with the rate of the theoretical CO(2) formation from
      uncatalyzed HCO(3)(-) conversion in the medium. The higher pH compensation point
      (10.3) and insensitivity of the photosynthetic rate to acetazolamide indicate
      that the alga has good capacity for direct HCO(3)(-) utilization. The
      photosynthetic rate reached 150 times the theoretical CO(2) supply rate at 100
      micromol L(-1) DIC (pH 9.0) in the presence of 10 mmol L(-1) K(+) and 46 times
      that in the absence of K(+), indicating that for pH 9.4-grown P. tricornutum,
      HCO(3)(-) in the medium is taken up through K(+)-dependent and -independent
      HCO(3)(-) transporters. The K(1/2) (CO(2)) values at pH 8.2 were about 4 times
      higher than those at pH 9.0, whereas the K(1/2) (HCO(3)(-)) values at pH 8.2 were
      slightly lower than those at pH 9.0 whether without or with K(+), providing
      further evidence for the presence of the two HCO(3)(-) transport patterns in this
      alga. Photosynthetic rate and affinity for HCO(3)(-) in the presence of K(+),
      respectively, were about 2- and 7-fold higher than those in the absence of K(+),
      indicating that K(+)-dependent HCO(3)(-) transport is a predominant pattern of
      HCO(3)(-) cellular uptake in low DIC concentration. However, as P. tricornutum
      was cultured at pH 7.2 or 8.0, photosynthetic affinities to HCO(3)(-) were not
      affected by K(+), implying that K(+)-dependent HCO(3)(-) transport is induced
      when P. tricornutum is cultured at high alkaline pH.

PMID- 16632590
TI  - WRI1 is required for seed germination and seedling establishment.
AB  - Storage compound accumulation during seed development prepares the next
      generation of plants for survival. Therefore, processes involved in the
      regulation and synthesis of storage compound accumulation during seed development
      bear relevance to germination and seedling establishment. The wrinkled1 (wri1)
      mutant of Arabidopsis (Arabidopsis thaliana) is impaired in seed oil
      accumulation. The WRI1 gene encodes an APETALA2/ethylene-responsive element
      binding protein transcription factor involved in the control of metabolism,
      particularly glycolysis, in the developing seeds. Here we investigate the role of
      this regulatory factor in seed germination and seedling establishment by
      comparing the wri1-1 mutant, transgenic lines expressing the WRI1 wild-type cDNA
      in the wri1-1 mutant background, and the wild type. Plants altered in the
      expression of the WRI1 gene showed different germination responses to the growth
      factor abscisic acid (ABA), sugars, and fatty acids provided in the medium.
      Germination of the mutant was more sensitive to ABA, sugars, and osmolites, an
      effect that was alleviated by increased WRI1 expression in transgenic lines. The
      expression of ABA-responsive genes AtEM6 and ABA-insensitive 3 (ABI3) was
      increased in the wri1-1 mutant. Double-mutant analysis between abi3-3 and wri1-1
      suggested that WRI1 and ABI3, a transcription factor mediating ABA responses in
      seeds, act in parallel pathways. Addition of 2-deoxyglucose inhibited seed
      germination, but did so less in lines overexpressing WRI1. Seedling establishment
      was decreased in the wri1-1 mutant but could be alleviated by sucrose. Apart from
      a possible signaling role in germination, sugars in the medium were required as
      building blocks and energy supply during wri1-1 seedling establishment.

PMID- 16632591
TI  - Large-scale analysis of mRNA translation states during sucrose starvation in
      arabidopsis cells identifies cell proliferation and chromatin structure as
      targets of translational control.
AB  - Sucrose starvation of Arabidopsis (Arabidopsis thaliana) cell culture was used to
      identify translationally regulated genes by DNA microarray analysis. Cells were
      starved by subculture without sucrose, and total and polysomal RNA was extracted
      between 6 and 48 h. Probes were derived from both RNA populations and used to
      screen oligonucleotide microarrays. Out of 25,607 screened genes, 224 were found
      to be differentially accumulated in polysomal RNA following starvation and 21
      were found to be invariant in polysomal RNA while their total RNA abundance was
      modified. Most of the mRNA appears to be translationally repressed (183/245
      genes), which is consistent with a general decrease in metabolic activities
      during starvation. The parallel transcriptional analysis identifies 268 regulated
      genes. Comparison of transcriptional and translational gene lists highlights the
      importance of translational regulation (mostly repression) affecting genes
      involved in cell cycle and cell growth, these being overrepresented in
      translationally regulated genes, providing a molecular framework for the arrest
      of cell proliferation following starvation. Starvation-induced translational
      control also affects chromatin regulation genes, such as the HD1 histone
      deacetylase, and the level of histone H4 acetylation was found to increase during
      starvation. This suggests that regulation of the global nuclear transcriptional
      activity might be linked to cytoplasmic translational regulations.

PMID- 16632592
TI  - The intracellular fate of a recombinant protein is tissue dependent.
AB  - Recombinant proteins directed to the secretory pathway in plants require a signal
      peptide for entry into the endoplasmic reticulum. In the absence of further
      targeting information, such proteins are generally secreted via the default
      pathway to the apoplast. This has been well documented in protoplasts and leaf
      tissue, but the trafficking of recombinant proteins in seeds and other storage
      tissues has rarely been investigated. We used Aspergillus niger phytase as a
      model glycoprotein to compare the intracellular fate of a recombinant protein in
      the leaves and seeds of rice (Oryza sativa). Using fluorescence and electron
      microscopy we showed that the recombinant protein was efficiently secreted from
      leaf cells as expected. In contrast, within endosperm cells it was retained in
      endoplasmic reticulum-derived prolamin bodies and protein storage vacuoles.
      Consistent with our immunolocalization data, the phytase produced in endosperm
      cells possessed oligomannose and vacuolar-type N-glycans
      [Man(3)(Xyl)(Fuc)GlcNAc(2)], whereas the phytase produced in leaves contained
      predominantly secretion-type N-glycans [GlcNAc(2)Man(3)(Xyl)(Fuc)GlcNAc(2)]. The
      latter could not be detected in preparations of the endosperm-derived phytase.
      Our results show that the intracellular deposition and modification of a
      recombinant protein is tissue dependent.

PMID- 16632593
TI  - Virus-induced gene silencing of argonaute genes in Nicotiana benthamiana
      demonstrates that extensive systemic silencing requires Argonaute1-like and
      Argonaute4-like genes.
AB  - Several distinct pathways of RNA silencing operate in plants with roles including
      the suppression of virus accumulation, control of endogenous gene expression, and
      direction of DNA and chromatin modifications. Proteins of the Dicer-Like and
      Argonaute (AGO) families have key roles within these silencing pathways and have
      distinct biochemical properties. We are interested in the relationships between
      different silencing pathways and have used Nicotiana benthamiana as a model
      system. While not being an amenable plant for traditional genetics, N.
      benthamiana is extensively used for RNA-silencing studies. Using virus-induced
      gene silencing technology we demonstrate that both NbAGO1- and NbAGO4-like genes
      are required for full systemic silencing but not for silencing directed by an
      inverted repeat transgene. Phenotypic differences between the virus-induced gene
      silencing plants indicate that NbAGO1 and NbAGO4 like act at different stages of
      the silencing pathways. Suppression of NbAGO1 expression recapitulated the
      hypomorphic mutant phenotype of certain Arabidopsis (Arabidopsis thaliana) ago1
      alleles, however, suppression of NbAgo4 like resulted in phenotypes differing in
      some respects from those reported for Arabidopsis ago4. We suggest that the small
      interfering RNA amplification step required for full systemic silencing is
      dependent upon a nuclear event requiring the activity of NbAGO4 like.

PMID- 16632594
TI  - Hypoxia or nutrient restriction during pregnancy in rats leads to progressive
      cardiac remodeling and impairs postischemic recovery in adult male offspring.
AB  - Intrauterine growth restriction (IUGR) increases the risk of developing adult
      onset cardiovascular disease. We hypothesized that IUGR resulting from maternal
      hypoxia or nutrient restriction during late gestation will produce cardiac
      remodeling and impair cardiac recovery after ischemia/reperfusion (I/R) in adult
      male offspring aged 4 or 7 mo. Sprague-Dawley rats were randomized on day 15 of
      pregnancy to hypoxia (IUGR-H, 12% oxygen), nutrient restriction (IUGR-NR, 40% of
      control diet) or control (room air) groups. In 4-mo IUGR-H offspring, left
      ventricular wt/body wt ratio (LVW/BW) and right ventricular wt/BW ratio (RVW/BW)
      increased, in association with increased collagen I and III expression, beta and
      alpha myosin heavy chain (beta/alphaMHC) ratio, and decreased matrix
      metalloproteinase (MMP)-2 activity compared to the other groups. Left ventricular
      end diastolic pressure was higher in perfused hearts. Functional recovery after
      I/R was remarkably reduced (10+/-3%) compared to both control (39+/-5%) and IUGR
      NR rats (32+/-4%). At 7 mo, both IUGR-H and IUGR-NR offspring had increased
      LVW/BW, collagen I and III, beta/alpha MHC ratio, and decreased cardiac recovery
      and MMP-2 activity compared to control. These findings suggest that hypoxia or
      undernutrition during development leads to pathological cardiac remodeling,
      diastolic dysfunction, and increased sensitivity to ischemic injury during adult
      life.

PMID- 16632595
TI  - Long-range multilocus haplotype phasing of the MHC.
AB  - Haplotypes are a powerful tool for identifying the genetic basis of common
      complex diseases. Disease-association mapping requires molecular methods for
      haplotyping biallelic SNP variation and highly complex polymorphisms. We
      developed a method for phasing HLA-A, HLA-B, and HLA-DRB1 alleles on chromosome 6
      in unrelated individuals. This method uses the highly polymorphic HLA-B locus to
      discriminate the two HLA haplotypes in heterozygous individuals and its ideal
      location 1.4 Mbp telomeric to HLA-DRB1 and 1.2 Mbp centromeric to HLA-A to
      capture 2-Mbp-long genomic DNA. Genomic DNA representing a single HLA-B-captured
      haplotype is genotyped for HLA-A and HLA-DRB1 alleles and linkage to HLA-B is
      established. Proof of principle was established in a large blinded study of phase
      known samples. Availability of an efficient method for MHC haplotype phase
      determination will facilitate the mapping of causative MHC-resident genes in many
      human diseases and has the potential to be broadened to other polymorphic gene
      complexes.

PMID- 16632596
TI  - Long-term self-renewal and directed differentiation of human embryonic stem cells
      in chemically defined conditions.
AB  - Chemically defined medium (CDM) conditions for controlling human embryonic stem
      cell (hESC) fate will not only facilitate the practical application of hESCs in
      research and therapy but also provide an excellent system for studying the
      molecular mechanisms underlying self-renewal and differentiation, without the
      multiple unknown and variable factors associated with feeder cells and serum.
      Here we report a simple CDM that supports efficient self-renewal of hESCs grown
      on a Matrigel-coated surface over multiple passages. Expanded hESCs under such
      conditions maintain expression of multiple hESC-specific markers, retain the
      characteristic hESC morphology, possess a normal karyotype in vitro, as well as
      develop teratomas in vivo. Additionally, several growth factors were found to
      selectively induce monolayer differentiation of hESC cultures toward neural,
      definitive endoderm/pancreatic and early cardiac muscle cells, respectively, in
      our CDM conditions. Therefore, this CDM condition provides a basic platform for
      further characterization of hESC self-renewal and directed differentiation, as
      well as the development of novel therapies.

PMID- 16632597
TI  - Expression profiling the developing mammalian enteric nervous system identifies
      marker and candidate Hirschsprung disease genes.
AB  - The enteric nervous system (ENS) is composed of neurons and glial cells,
      organized as interconnected ganglia within the gut wall, which controls
      peristalsis of the gut wall and secretions from its glands. The Ret receptor
      tyrosine kinase is expressed throughout enteric neurogenesis and is required for
      normal ENS development; humans with mutations in the RET locus have Hirschsprung
      disease (HSCR, an absence of ganglia in the colon), and mice lacking Ret have
      total intestinal aganglionosis. The Ret mutant mouse provides a tool for
      identifying genes implicated in development of the ENS. By using RNA from WT and
      Ret mutant (aganglionic) gut tissue and DNA microarrays, we have conducted a
      differential screen for ENS-expressed genes and have identified hundreds of
      candidate ENS-expressed genes. Forty-seven genes were selected for further
      analysis, representing diverse functional classes. We show that all of the
      analyzed genes are expressed in the ENS and that the screen was sensitive enough
      to identify genes marking only subpopulations of ENS cells. Our screen,
      therefore, was reliable and sensitive and has identified many previously
      undescribed genes for studying ENS development. Moreover, two of the genes
      identified in our screen Arhgef3 and Ctnnal1, have human homologues that map to
      previously identified HSCR susceptibility loci, thus representing excellent
      candidates for HSCR genes. This comprehensive profile of ENS gene expression
      refines our understanding of ENS development and serves as a resource for future
      developmental, biochemical, and human genetic studies.

PMID- 16632598
TI  - Genomewide comparative analysis of alternative splicing in plants.
AB  - Alternative splicing (AS) has been extensively studied in mammalian systems but
      much less in plants. Here we report AS events deduced from EST/cDNA analysis in
      two model plants: Arabidopsis and rice. In Arabidopsis, 4,707 (21.8%) of the
      genes with EST/cDNA evidence show 8,264 AS events. Approximately 56% of these
      events are intron retention (IntronR), and only 8% are exon skipping. In rice,
      6,568 (21.2%) of the expressed genes display 14,542 AS events, of which 53.5% are
      IntronR and 13.8% are exon skipping. The consistent high frequency of IntronR
      suggests prevalence of splice site recognition by intron definition in plants.
      Different AS events within a given gene occur, for the most part, independently.
      In total, 36-43% of the AS events produce transcripts that would be targets of
      the non-sense-mediated decay pathway, if that pathway were to operate in plants
      as in humans. Forty percent of Arabidopsis AS genes are alternatively spliced
      also in rice, with some examples strongly suggesting a role of the AS event as an
      evolutionary conserved mechanism of posttranscriptional regulation. We created a
      comprehensive web-interfaced database to compile and visualize the evidence for
      alternative splicing in plants (Alternative Splicing in Plants, available at
      www.plantgdb.org/ASIP).

PMID- 16632599
TI  - Evidence for metabolic and reproductive phenotypes in mothers of women with
      polycystic ovary syndrome.
AB  - Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its
      pathogenesis remains controversial. We performed this study of mothers of women
      with PCOS to test the hypothesis that dyslipidemia is a heritable trait in
      families of women with PCOS and to investigate the impact of age on reproductive
      and metabolic phenotypes. Fasting blood was obtained in 215 non-Hispanic white
      mothers of women with PCOS and 62 control women. The prevalence of metabolic
      syndrome was compared with that in non-Hispanic white women of comparable age
      from the National Health and Nutrition Examination Survey III. Mothers had higher
      total (P < 0.001) and low-density lipoprotein (LDL) cholesterol levels (P =
      0.007), whereas high-density lipoprotein and triglyceride levels did not differ
      compared with control women. The only predictors of LDL levels in mothers were
      their daughters' LDL levels (r2 = 0.11, P < 0.001) and their own unbound
      testosterone levels (r2 = 0.04, P = 0.03). The prevalence of metabolic syndrome
      was increased in obese (body mass index > or = 30 kg/m2) mothers compared with
      obese non-Hispanic white women from the National Health and Nutrition Examination
      Survey III (P = 0.04). Thirty-one percent of mothers reported a history of
      menstrual irregularity. These mothers had higher androgen levels, markers of
      insulin resistance, and LDL levels than mothers with regular menses. LDL levels
      are increased in mothers of women with PCOS, suggestive of a heritable trait. A
      history of menstrual irregularity identifies mothers with features of PCOS. Obese
      mothers have a very high prevalence of metabolic syndrome. These findings suggest
      that both the reproductive and metabolic abnormalities persist with age in PCOS.

PMID- 16632600
TI  - Histidines, heart of the hydrogen ion channel from influenza A virus: toward an
      understanding of conductance and proton selectivity.
AB  - The heart of the H+ conductance mechanism in the homotetrameric M2 H+ channel
      from influenza A is a set of four histidine side chains. Here, we show that
      protonation of the third of these imidazoles coincides with acid activation of
      this transmembrane channel and that, at physiological pH, the channel is closed
      by two imidazole-imidazolium dimers, each sharing a low-barrier hydrogen bond.
      This unique construct succeeds in distributing a pair of charges over four rings
      and many atoms in a low dielectric environment to minimize charge repulsion.
      These dimers form with identical pKas of 8.2 +/- 0.2, suggesting cooperative H+
      binding and clearly illustrating high H+ affinity for this channel. The
      protonation behavior of the histidine side chains has been characterized by using
      solid-state NMR spectroscopy on the M2 transmembrane domain in fully hydrated
      lipid bilayers where the tetrameric backbone structure is known. Furthermore,
      electrophysiological measurements of multichannel and single-channel experiments
      confirm that these protein constructs are functional.

PMID- 16632601
TI  - An integrated approach for risk profiling and spatial prediction of Schistosoma
      mansoni-hookworm coinfection.
AB  - Multiple-species parasitic infections are pervasive in the developing world, yet
      resources for their control are scarce. We present an integrated approach for
      risk profiling and spatial prediction of coinfection with Schistosoma mansoni and
      hookworm for western Cote d'Ivoire. Our approach combines demographic,
      environmental, and socioeconomic data; incorporates them into a geographic
      information system; and employs spatial statistics. Demographic and socioeconomic
      data were obtained from education registries and from a questionnaire
      administered to schoolchildren. Environmental data were derived from remotely
      sensed satellite images and digitized ground maps. Parasitologic data, obtained
      from fecal examination by using two different diagnostic approaches, served as
      the outcome measure. Bayesian variogram models were used to assess risk factors
      and spatial variation of S. mansoni-hookworm coinfection in relation to
      demographic, environmental, and socioeconomic variables. Coinfections were found
      in 680 of 3,578 schoolchildren (19.0%) with complete data records. The prevalence
      of monoinfections with either hookworm or S. mansoni was 24.3% and 24.1%,
      respectively. Multinomial Bayesian spatial models showed that age, sex,
      socioeconomic status, and elevation were good predictors for the spatial
      distribution of S. mansoni-hookworm coinfection. We conclude that our integrated
      approach, employing a diversity of data sources, geographic information system
      and remote sensing technologies, and Bayesian spatial statistics, is a powerful
      tool for risk profiling and spatial prediction of S. mansoni-hookworm
      coinfection. More generally, this approach facilitates risk mapping and
      prediction of other parasite combinations and multiparasitism, and hence can
      guide integrated disease control programs in resource-constrained settings.

PMID- 16632602
TI  - Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T
      cells.
AB  - Toll-like receptors (TLRs) are primary sensors of both innate and adaptive immune
      systems and play a pivotal role in response against structurally conserved
      components of pathogens. Synthetic bacterial lipoprotein (BLP) Pam3Cys-SK4 is a
      TLR2 agonist that is capable of modulating T cell immune responses. We show here
      that BLP, together with anti-CD3 antibody [T cell receptor (TcR) activation],
      induced proliferation of both CD4+ CD25+ regulatory T cells (Tregs) and CD4+ CD25
      (effector) T cells in the absence of antigen-presenting cells. The expanded
      Tregs showed a transient loss of suppressive activity. Moreover, BLP rendered
      effectors resistant to the suppression of Tregs by increasing IL-2 secretion. BLP
      also transiently suppressed the induction of Foxp3 (X-linked forkhead/winged
      helix transcription factor) mRNA in Tregs at the first 8-15 h after T cell
      receptor activation. Consistent with this observation, BLP-stimulated Tregs
      regained their inhibitory activity and prevented spontaneous colitis induced by
      effectors in severe combined immunodeficient mice. Our results demonstrate a
      previously unrecognized pathway by which TLR expressed on T cells may directly
      modulate the immune response. Thus, during an acute bacterial infection, BLP may
      rapidly increase the host's adaptive immunity by expanding effectors and also by
      attenuating the suppressive activity of Tregs. In the process, BLP also expands
      the Tregs, which recover their suppressive activity when the infection has
      subsided, in time to limit potential autoimmunity that might result from the
      overactivated effectors.

PMID- 16632603
TI  - Field-dependent ordered phases and Kondo phenomena in the filled skutterudite
      compound PrOs4As12.
AB  - Electrical resistivity, specific heat, and magnetization measurements to
      temperatures as low as 80 mK and magnetic fields up to 16 T were made on the
      filled skutterudite compound PrOs4As12. The measurements reveal the presence of
      two ordered phases at temperatures below approximately 2.3 K and in fields below
      approximately 3 T. Neutron-scattering experiments in zero field establish an
      antiferromagnetic ground state < 2.28 K. In the antiferromagnetically ordered
      state, the electronic-specific heat coefficient gamma approximately 1 J/mol x K2
      below 1.6 K and 0 < or = H < or = 1.25 T. The temperature and magnetic-field
      dependence of the electrical resistivity and specific heat in the paramagnetic
      state are consistent with single-ion Kondo behavior with a low Kondo temperature
      on the order of 1 K. The electronic-specific heat in the paramagnetic state can
      be described by the resonance-level model with a large zero-temperature
      electronic-specific heat coefficient that decreases with increasing magnetic
      field from approximately 1 J/mol x K2 at 3 T to approximately 0.2 J/mol x K2 at
      16 T.

PMID- 16632604
TI  - Differential expression of IFN-alpha and TRAIL/DR5 in lymphoid tissue of
      progressor versus nonprogressor HIV-1-infected patients.
AB  - Loss of CD4+ T cells, the hallmark of HIV pathogenesis, was suggested to be
      partly due to apoptosis. We recently reported that IFN-alpha produced by HIV-1
      activated plasmacytoid dendritic cells (pDCs) contributes to CD4+ T cell
      apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor
      (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN
      alpha in pDCs is coupled to increased expression of IFN regulatory factor 7 and
      MyD88 by pDCs in vivo and in vitro. Expression of IFN-alpha was increased in
      lymphoid tonsillar tissue (LT) of patients with progressive (HIV(prog)) compared
      with nonprogressive (HIV(NP)) HIV-1 disease and to uninfected controls. LT from
      HIV(prog) exhibited higher TRAIL and DR5 mRNA levels than LT from HIV(NP) or
      controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that
      HIV-1 induces IFN-alpha and the TRAIL/DR5 apoptotic pathway in LT, suggesting a
      role for these cytokines in HIV-1 immunopathogenesis.

PMID- 16632605
TI  - Beneficial and perverse effects of isoniazid preventive therapy for latent
      tuberculosis infection in HIV-tuberculosis coinfected populations.
AB  - In sub-Saharan Africa, where the emergence of HIV has caused dramatic increases
      in tuberculosis (TB) case notifications, new strategies for TB control are
      necessary. Isoniazid preventive therapy (IPT) for HIV-TB coinfected individuals
      reduces the reactivation of latent Mycobacterium tuberculosis infections and is
      being evaluated as a potential community-wide strategy for improving TB control.
      We developed a mathematical model of TB/HIV coepidemics to examine the impact of
      community-wide implementation of IPT for TB-HIV coinfected individuals on the
      dynamics of drug-sensitive and -resistant TB epidemics. We found that community
      wide IPT will reduce the incidence of TB in the short-term but may also speed the
      emergence of drug-resistant TB. We conclude that community-wide IPT in areas of
      emerging HIV and drug-resistant TB should be coupled with diagnostic and
      treatment policies designed to identify and effectively treat the increasing
      proportion of patients with drug-resistant TB.

PMID- 16632606
TI  - Time-resolved vibrational spectroscopy detects protein-based intermediates in the
      photosynthetic oxygen-evolving cycle.
AB  - Photosynthetic oxygen production by photosystem II (PSII) is responsible for the
      maintenance of aerobic life on earth. The production of oxygen occurs at the PSII
      oxygen-evolving complex (OEC), which contains a tetranuclear manganese (Mn)
      cluster. Photo-induced electron transfer events in the reaction center lead to
      the accumulation of oxidizing equivalents on the OEC. Four sequential
      photooxidation reactions are required for oxygen production. The oxidizing
      complex cycles among five oxidation states, called the S(n) states, where n
      refers to the number of oxidizing equivalents stored. Oxygen release occurs
      during the S(3)-to-S(0) transition from an unstable intermediate, known as the
      S(4) state. In this report, we present data providing evidence for the production
      of an intermediate during each S state transition. These protein-derived
      intermediates are produced on the microsecond to millisecond time scale and are
      detected by time-resolved vibrational spectroscopy on the microsecond time scale.
      Our results suggest that a protein-derived conformational change or proton
      transfer reaction precedes Mn redox reactions during the S(2)-to-S(3) and S(3)-to
      S(0) transitions.

PMID- 16632607
TI  - Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral
      dystrophy patients versus normal human myoblasts.
AB  - Fascioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant
      neuromuscular disorder linked to partial deletion of integral numbers of a 3.3 kb
      polymorphic repeat, D4Z4, within the subtelomeric region of chromosome 4q.
      Although the relationship between deletions of D4Z4 and FSHD is well established,
      how this triggers the disease remains unclear. We have mapped the DNA loop domain
      containing the D4Z4 repeat cluster in human primary myoblasts and in murine-human
      hybrids. A nuclear matrix attachment site was found located in the vicinity of
      the repeat. Prominent in normal human myoblasts and nonmuscular human cells, this
      site is much weaker in muscle cells derived from FSHD patients, suggesting that
      the D4Z4 repeat array and upstream genes reside in two loops in nonmuscular cells
      and normal human myoblasts but in only one loop in FSHD myoblasts. We propose a
      model whereby the nuclear scaffold/matrix attached region regulates chromatin
      accessibility and expression of genes implicated in the genesis of FSHD.

PMID- 16632608
TI  - Binding of 5'-GTP to the C-terminal FeS cluster of the radical S
      adenosylmethionine enzyme MoaA provides insights into its mechanism.
AB  - The first step in molybdenum cofactor biosynthesis, the conversion of 5'-GTP to
      precursor Z, an oxygen-sensitive tetrahydropyranopterin is catalyzed by the S
      adenosylmethionine (SAM)-dependent enzyme MoaA and the accessory protein MoaC.
      This reaction involves the radical-initiated intramolecular rearrangement of the
      guanine C8 atom. MoaA harbors an N-terminal [4Fe-4S] cluster, which is involved
      in the reductive cleavage of SAM and generates a 5'-deoxyadenosyl radical (5'
      dA*), and a C-terminal [4Fe-4S] cluster presumably involved in substrate binding
      and/or activation. Biochemical studies identified residues involved in 5'-GTP
      binding and the determinants of nucleotide specificity. The crystal structure of
      MoaA in complex with 5'-GTP confirms the biochemical data and provides valuable
      insights into the subsequent radical reaction. MoaA binds 5'-GTP with high
      affinity and interacts through its C-terminal [4Fe-4S] cluster with the guanine
      N1 and N2 atoms, in a yet uncharacterized binding mode. The tightly anchored
      triphosphate moiety prevents the escape of radical intermediates. This structure
      also visualizes the L-Met and 5'-dA cleavage products of SAM. Rotation of the 5'
      dA ribose and/or conformational changes of the guanosine are proposed to bring
      the 5'-deoxyadenosyl radical into close proximity of either the ribose C2' and
      C3' or the guanine C8 carbon atoms leading to hydrogen abstraction.

PMID- 16632609
TI  - Weak selection and recent mutational changes influence polymorphic synonymous
      mutations in humans.
AB  - Recent large-scale genomic and evolutionary studies have revealed the small but
      detectable signature of weak selection on synonymous mutations during mammalian
      evolution, likely acting at the level of translational efficacy (i.e.,
      translational selection). To investigate whether weak selection, and
      translational selection in particular, plays any role in shaping the fate of
      synonymous mutations that are present today in human populations, we studied
      genetic variation at the polymorphic level and patterns of evolution in the human
      lineage after human-chimpanzee separation. We find evidence that neutral
      mechanisms are influencing the frequency of polymorphic mutations in humans. Our
      results suggest a recent increase in mutational tendencies toward AT, observed in
      all isochores, that is responsible for AT mutations segregating at lower
      frequencies than GC mutations. In all, however, changes in mutational tendencies
      and other neutral scenarios are not sufficient to explain a difference between
      synonymous and noncoding mutations or a difference between synonymous mutations
      potentially advantageous or deleterious under a translational selection model.
      Furthermore, several estimates of selection intensity on synonymous mutations all
      suggest a detectable influence of weak selection acting at the level of
      translational selection. Thus, random genetic drift, recent changes in mutational
      tendencies, and weak selection influence the fate of synonymous mutations that
      are present today as polymorphisms. All of these features, neutral and selective,
      should be taken into account in evolutionary analyses that often assume constancy
      of mutational tendencies and complete neutrality of synonymous mutations.

PMID- 16632610
TI  - Remote sensing of future competitors: impacts on plant defenses.
AB  - Far-red radiation (FR) reflected by green tissues is a key signal that plants use
      to detect the proximity of future competitors. Perception of increased levels of
      FR elicits a suite of responses collectively known as the shade-avoidance
      syndrome, which includes increased stem elongation, production of erect leaves,
      and reduced lateral branching. These responses improve the access to light for
      plants that occur in crowded populations. Responses to the proximity of
      competitors are known to affect the susceptibility to disease and predation in
      several organisms, including social animals. However, the impacts of warning
      signals of competition on the expression of defenses have not been explicitly
      investigated in plants. In the experiments reported here, we show that reflected
      FR induced a dramatic down-regulation of chemical defenses in wild tobacco
      (Nicotiana longiflora). FR altered the expression of several defense-related
      genes, inhibited the accumulation of herbivore-induced phenolic compounds, and
      augmented the performance of the specialist herbivore Manduca sexta.
      Complementary studies with tomato suggested that the effects of FR on defenses
      are mediated by the photoreceptor phytochrome B. The central implication of these
      results is that shade-intolerant species such as wild tobacco and tomato activate
      functional changes that affect their ability to cope with herbivore attack in
      response to phytochrome signals of future competition, even in the absence of
      real competition for resources. These findings suggest that competition
      overshadowed herbivory during the evolution of this group of species and add a
      new axis to the definition of the shade-avoidance syndrome.

PMID- 16632611
TI  - Microsaccades are triggered by low retinal image slip.
AB  - Even during visual fixation of a stationary target, our eyes perform rather
      erratic miniature movements, which represent a random walk. These "fixational"
      eye movements counteract perceptual fading, a consequence of fast adaptation of
      the retinal receptor systems to constant input. The most important contribution
      to fixational eye movements is produced by microsaccades; however, a specific
      function of microsaccades only recently has been found. Here we show that the
      occurrence of microsaccades is correlated with low retinal image slip
      approximately 200 ms before microsaccade onset. This result suggests that
      microsaccades are triggered dynamically, in contrast to the current view that
      microsaccades are randomly distributed in time characterized by their rate-of
      occurrence of 1 to 2 per second. As a result of the dynamic triggering mechanism,
      individual microsaccade rate can be predicted by the fractal dimension of
      trajectories. Finally, we propose a minimal computational model for the dynamic
      triggering of microsaccades.

PMID- 16632612
TI  - Computational and neurobiological mechanisms underlying cognitive flexibility.
AB  - The ability to switch between multiple tasks is central to flexible behavior.
      Although switching between tasks is readily accomplished, a well established
      consequence of task switching (TS) is behavioral slowing. The source of this
      switch cost and the contribution of cognitive control to its resolution remain
      highly controversial. Here, we tested whether proactive interference arising from
      memory places fundamental constraints on flexible performance, and whether
      prefrontal control processes contribute to overcoming these constraints. Event
      related functional MRI indexed neural responses during TS. The contributions of
      cognitive control and interference were made theoretically explicit in a
      computational model of task performance. Model estimates of two levels of
      proactive interference, "conceptual conflict" and "response conflict," produced
      distinct preparation-related profiles. Left ventrolateral prefrontal cortical
      activation paralleled model estimates of conceptual conflict, dissociating from
      that in left inferior parietal cortex, which paralleled model estimates of
      response conflict. These computationally informed neural measures specify
      retrieved conceptual representations as a source of conflict during TS and
      suggest that left ventrolateral prefrontal cortex resolves this conflict to
      facilitate flexible performance.

PMID- 16632613
TI  - Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from
      Pseudomonas aeruginosa.
AB  - Pathogenic gram-negative bacteria can modify the lipid A portion of their
      lipopolysaccharide in response to environmental stimuli. 3-O-deacylation of lipid
      A by the outer membrane enzyme PagL modulates signaling through Toll-like
      receptor 4, leading to a reduced host immune response. We found that PagL is
      widely disseminated among gram-negative bacteria. Only four residues are
      conserved: a Ser, His, Phe, and Asn residue. Here, we describe the crystal
      structure of PagL from Pseudomonas aeruginosa to 2.0-A resolution. It consists of
      an eight-stranded beta-barrel with the axis tilted by approximately 30 degrees
      with respect to the lipid bilayer. The structure reveals that PagL contains an
      active site with a Ser-His-Glu catalytic triad and an oxyanion hole that
      comprises the conserved Asn. The importance of active site residues was confirmed
      in mutagenesis studies. Although PagL is most likely active as a monomer, its
      active site architecture shows high resemblance to that of the dimeric 12
      stranded outer membrane phospholipase A. Modeling of the substrate lipid X onto
      the active site reveals that the 3-O-acyl chain is accommodated in a hydrophobic
      groove perpendicular to the membrane plane. In addition, an aspartate makes a
      hydrogen bond with the hydroxyl group of the 3-O-acyl chain, probably providing
      specificity of PagL toward lipid A.

PMID- 16632614
TI  - Commentary: PET poised to alter the current paradigm for response assessment of
      non-Hodgkin's lymphoma.

PMID- 16632615
TI  - Acute adverse reactions to magnetic resonance contrast media--gadolinium
      chelates.
AB  - The objective of this study was to evaluate the clinical safety of intravenous
      gadolinium-based contrast media used in patients who underwent MRI at a single
      institution. Acute adverse reactions to intravenous gadolinium-based contrast
      media used for MRI at the Princess Margaret Hospital, Hong Kong, SAR, from
      January 1999 to November 2004 were recorded in an incidence log book. The medical
      records of patients' demographics were retrospectively reviewed and the nature,
      frequency and severity of the adverse reactions were investigated and documented.
      The incidence of acute adverse reactions to intravenous gadolinium-based contrast
      media was 0.48% (45 patients with 46 adverse reactions). The severity of these
      adverse reactions were 96% mild, 2% moderate (one patient developed shortness of
      breath that required oxygen supplementation and intravenous steroidal management)
      and 2% severe (one patient developed an anaphylactoid reaction, but successfully
      recovered through timely resuscitation). No patients were recorded as having
      contrast extravasation and none died as a result of any adverse reaction. Among
      the 45 patients who developed adverse reactions, three patients (6.7%) had prior
      adverse reactions to iodinated contrast media, three (6.7%) had prior reactions
      to a different gadolinium-based contrast agent, one (2%) had asthma and nine
      (20%) had a history of drug/food allergy. Overall, 41% of the adverse reactions
      were not documented in the final MRI report or the clinical medical records.
      Gadolinium-based contrast media are safe and well tolerated by the vast majority
      of patients. In our study, the adverse reaction rate (0.48%) and the incidence of
      severe anaphylactoid reaction (0.01%) concur with those reported in the
      literature. Although most of the symptoms are mild and transient, these adverse
      reactions must be accurately documented and managed.

PMID- 16632616
TI  - Observer variation in the evaluation of lumbar herniated discs and root
      compression: spiral CT compared with MRI.
AB  - Spiral CT is considered the best alternative for MRI in the evaluation of
      herniated discs. The purpose of this study was to compare radiological evaluation
      of spiral CT with MRI in patients suspected of herniated discs. 57 patients with
      lumbosacral radicular syndrome underwent spiral CT and 1.5 T MRI. Two
      neuroradiologists independently evaluated 171 intervertebral discs for herniation
      or "bulge" and 456 nerve roots for root compression, once after CT and once after
      MRI. We compared interobserver agreement using the kappa statistic and we
      performed a paired comparison between CT and MRI. For detection of herniated or
      bulging discs, we observed no significant difference in interobserver agreement
      (CT kappa 0.66 vs MRI kappa 0.71; p = 0.40). For root compression, we observed
      significantly better interobserver agreement at MRI evaluation (CT kappa 0.59 vs
      MRI kappa 0.78; p = 0.01). In 30 of 171 lumbar discs (18%) and in 54 of 456 nerve
      roots (12%), the observers disagreed on whether CT results were similar to MRI.
      In the cases without disagreement, CT differed from MRI in 6 discs (3.5%) and in
      3 nerve roots (0.7%). For radiological evaluation of lumbar herniated discs, we
      found no evidence that spiral CT is inferior to MRI. For evaluating lumbar nerve
      root compression, spiral CT is less reliable than MRI.

PMID- 16632617
TI  - Initial experiences of using an automated volumetric measure of breast density:
      the standard mammogram form.
AB  - Limitations of area based measures of breast density have led several research
      groups to develop volumetric measures of breast density, for use in predicting
      risk and in epidemiological research. In this paper, we describe our initial
      experiences using an automated algorithm (standard mammogram form, SMF) to
      estimate the volume of the breast that is dense from digitized film mammograms.
      We performed analyses on 3816 mammograms of 626 women, who were part of the
      Glasgow Alumni Cohort and had mammograms taken within the Scottish Breast
      Screening Programme between 1989 and 2002. Absolute volume of dense breast tissue
      (SMF volume) and the percentage of the volume of the breast that is dense (SMF%)
      were calculated. The median (interquartile range) of SMF volume was 66 cm3 (48 to
      98), and of SMF% was 23.4% (18.6 to 29.7). SMF%, but not SMF volume, was
      positively related to a six category classification (SCC) of visually assigned
      area-based breast density (increase in ln(SMF%) per category increase in SCC:
      0.04% (95% CI: 0.03-0.05). The SMF algorithm produced lower SMF volume for
      craniocaudal (CC) compared with mediolateral oblique (MLO) views, but CC/MLO
      differences for SMF% were small. The mean right/left difference for ln(SMF
      volume) was -0.027 cm3 (95% confidence interval (CI) -0.044 to -0.009) and of
      ln(SMF%) was 0.005% (95% CI -0.008% to 0.019%). We present these initial data as
      a background for future analytical work using SMF.

PMID- 16632618
TI  - Occupational radiation doses in interventional cardiology: a 15-year follow-up.
AB  - This report describes occupational radiation doses of interventional
      cardiologists over 15 years and assesses action undertaken to optimize radiation
      protection. Personal dosimetry records of nine staff cardiologists and eight
      interventional cardiology fellows were recorded using personal dosemeters worn
      over and under their lead aprons. The hospital in which this study was conducted
      currently performs 5000 cardiology procedures per year. The hospital has improved
      its facilities since 1989, when it had two old-fashioned theatres, to include
      four rooms with more advanced and safer equipment. Intensive radiation protection
      training was also implemented since 1989. Initially, some individual dose values
      in the range of 100-300 mSv month(-1), which risked exceeding some regulatory
      dose limits, were measured over the lead apron. Several doses in the range of 5
      11 mSv month(-1) were recorded under the apron (mean = 10.2 mSv year(-1)). During
      the last 5 years of the study, after the implementation of the radiation
      protection actions and a programme of patient-dose optimization, the mean dose
      under the apron was reduced to 1.2 mSv year(-1). Current mean occupational doses
      recorded under the lead apron are 14% of those recorded during 1989-1992 and
      those recorded over the apron are 14-fold less than those recorded during 1989
      1992. The regulatory dose limits and the threshold for lens injuries might have
      been exceeded if radiation protection facilities had not been used
      systematically. The most effective actions involved in reducing the radiation
      risk were training in radiation protection, a programme of patient-dose reduction
      and the systematic use of radiation protection facilities, specifically ceiling
      suspended protective screens.

PMID- 16632619
TI  - A four-dimensional computer simulation model of the in vivo response to
      radiotherapy of glioblastoma multiforme: studies on the effect of clonogenic cell
      density.
AB  - Tumours behave as complex, self-organizing, opportunistic dynamic systems. In an
      attempt to better understand and describe the highly complicated tumour
      behaviour, a novel four-dimensional simulation model of in vivo tumour growth and
      response to radiotherapy has been developed. This paper presents the latest
      improvements to the model as well as a parametric validation of it. Improvements
      include an advanced algorithm leading to conformal tumour shrinkage, a
      quantitative consideration of the influence of oxygenation on radiosensitivity
      and a more realistic, imaging based description of the neovasculature
      distribution. The tumours selected for the validation of the model are a wild
      type and a mutated p53 gene glioblastomas multiforme. According to the model
      predictions, a whole tumour with larger cell cycle duration tends to repopulate
      more slowly. A lower oxygen enhancement ratio value leads to a more
      radiosensitive whole tumour. Higher clonogenic cell density (CCD) produces a
      higher number of proliferating tumour cells and, therefore, a more difficult
      tumour to treat. Simulation predictions agree at least semi-quantitatively with
      clinical experience, and particularly with the outcome of the Radiation Therapy
      Oncology Group (RTOG) Study 83-02. It is stressed that the model allows a
      quantitative study of the interrelationship between the competing influences in a
      complex, dynamic tumour environment. Therefore, the model can already be useful
      as an educational tool with which to study, understand and demonstrate the role
      of various parameters in tumour growth and response to irradiation. A long term
      quantitative clinical adaptation and validation of the model aiming at its
      integration into the treatment planning procedure is in progress.

PMID- 16632620
TI  - A quantitative study of IMRT delivery effects in commercial planning systems for
      the case of oesophagus and prostate tumours.
AB  - This study focuses on understanding the impact of intensity-modulated
      radiotherapy (IMRT) delivery effects when applied to plans generated by
      commercial treatment-planning systems such as Pinnacle (ADAC Laboratories Inc.)
      and CadPlan/Helios (Varian Medical Systems). These commercial planning systems
      have had several version upgrades (with improvements in the optimization
      algorithm), but the IMRT delivery effects have not been incorporated into the
      optimization process. IMRT delivery effects include head-scatter fluence from
      IMRT fields, transmission through leaves and the effect of the rounded shape of
      the leaf ends. They are usually accounted for after optimization when leaf
      sequencing the "optimal" fluence profiles, to derive the delivered fluence
      profile. The study was divided into two main parts: (a) analysing the dose
      distribution within the planning-target volume (PTV), produced by each of the
      commercial treatment-planning systems, after the delivered fluence had been
      renormalized to deliver the correct dose to the PTV; and (b) studying the impact
      of the IMRT delivery technique on the surrounding critical organs such as the
      spinal cord, lungs, rectum, bladder etc. The study was performed for tumours of
      (i) the oesophagus and (ii) the prostate and pelvic nodes. An oesophagus case was
      planned with the Pinnacle planning system for IMRT delivery, via multiple-static
      fields (MSF) and compensators, using the Elekta SL25 with a multileaf collimator
      (MLC) component. A prostate and pelvic nodes IMRT plan was performed with the
      Cadplan/Helios system for a dynamic delivery (DMLC) using the Varian 120-leaf
      Millennium MLC. In these commercial planning systems, since IMRT delivery effects
      are not included into the optimization process, fluence renormalization is
      required such that the median delivered PTV dose equals the initial prescribed
      PTV dose. In preparing the optimum fluence profile for delivery, the PTV dose has
      been "smeared" by the IMRT delivery techniques. In the case of the oesophagus,
      the critical organ, spinal cord, received a greater dose than initially planned,
      due to the delivery effects. The increase in the spinal cord dose is of the order
      of 2-3 Gy. In the case of the prostate and pelvic nodes, the IMRT delivery
      effects led to an increase of approximately 2 Gy in the dose delivered to the
      secondary PTV, the pelvic nodes. In addition to this, the small bowel, rectum and
      bladder received an increased dose of the order of 2-3 Gy to 50% of their total
      volume. IMRT delivery techniques strongly influence the delivered dose
      distributions for the oesophagus and prostate/pelvic nodes tumour sites and these
      effects are not yet accounted for in the Pinnacle and the CadPlan/Helios planning
      systems. Currently, they must be taken into account during the optimization stage
      by altering the dose limits accepted during optimization so that the final
      (sequenced) dose is within the constraints.

PMID- 16632621
TI  - Effect of ticlopidine in the prevention of radiation enteropathy.
AB  - Impairment of vascular function is considered to play an important role in
      chronic radiation enteropathy. In this experimental study, the role of
      ticlopidine, an inhibitor of ADP-induced platelet aggregation, was investigated
      in radiation enteropathy. 80 male Wistar albino rats, each weighing 170-200 g,
      were divided into four groups: (a) radiation alone (n = 20); (b) radiotherapy
      plus ticlopidine (n = 20); (c) ticlopidine control (n = 20) and (d) control (n =
      20). Both radiation groups received 19 Gy radiation to the exteriorized
      intestinal segments in a single fraction. Ticlopidine or vehicle was administered
      12 h after radiotherapy and continued for 1 month. Rats from every group were
      euthanized randomly at intervals of 6 weeks from 2 weeks to 26 weeks.
      Histopathological radiation injury was assessed using radiation injury scoring
      (RIS). Radiation with ticlopidine or radiation alone groups showed significant
      RIS deterioration compared with controls in all time points studied. Comparison
      of median RIS of radiotherapy and radiotherapy+ticlopidine groups at the 2nd,
      14th and 26th weeks yielded statistically significant RIS in favour of
      radiotherapy+ticlopidine group (p = 0.05). However, these differences were less
      pronounced at the 8th and 20th week (p = 0.07). Both radiation groups had poor
      weight gain when compared with control and ticlopidine groups. The weight gain in
      radiotherapy+ticlopidine group was significantly superior to only radiation group
      between 10th and 20th weeks (p = 0.05). This study showed that inhibition of
      platelet aggregation with ticlopidine might be useful in radiation enteropathy.
      However, the precise role of antiaggregant therapies on radiation enteropathy
      should be comprehensively studied before clinical consideration.

PMID- 16632622
TI  - Radioprotective effects of hesperidin against gamma irradiation in mouse bone
      marrow cells.
AB  - The radioprotective effects of hesperidin (HES), a flavonone glucoside, were
      investigated by using the micronucleus test for anticlastogenic and cell
      proliferation activity. A single intraperitoneal (ip) administration of
      hesperidin at doses of 10 mg kg(-1), 20 mg kg(-1), 40 mg kg(-1), 80 mg kg(-1) and
      160 mg kg(-1) 45 min prior to gamma irradiation (2 Gy) reduced the frequencies of
      micronuleated polychromatic erythrocytes (MnPCEs). All five doses of HES
      significantly reduced the frequencies of MnPCEs and increased PCE/PCE+NCE ratio
      in mice bone marrow compared with non-drug-treated irradiated control (p<0.0001).
      There was a drug dose-response effect of HES in reducing MnPCE and increasing the
      PCE/PCE+NCE ratio in bone marrow cells. The maximum reduction in MnPCE was
      observed in mice treated with HES at a dose of 80 mg kg(-1). The total MnPCE
      values were 2.85 fold less in the 80 mg kg(-1) HES group after being exposed to 2
      Gy of gamma-rays than those in the respective irradiated control. Our study
      demonstrates that hesperidin has powerful protective effects on the radiation
      induced DNA damage and on the decline in cell proliferation in mouse bone marrow.

PMID- 16632623
TI  - Characteristics and predictive factors of early-onset diarrhoea during pelvic
      irradiation.
AB  - This study reported characteristics and predictive factors of early-onset
      diarrhoea in patients receiving pelvic irradiation. We retrospectively reviewed
      229 patients undergoing radiotherapy alone for cervical or uterine cancer. Oral
      barium was taken 90 min before simulation. According to contrast medium within
      small intestine only or colon in simulation films, we categorised patients as
      normal and rapid transit groups. Small or large volume of small-bowel was also
      evaluated according to barium distribution of simulation films. Whole-pelvic
      irradiation (39.6-45 Gy/22-25 fractions) was delivered to all patients initially.
      We recorded the onset of diarrhoea during pelvic irradiation. The rates of early
      onset diarrhoea (<10 Gy) were compared between these two groups. The incidence of
      diarrhoea before 10 Gy was 7% and 17% (p = 0.138) in patients with normal and
      rapid transit, respectively. In multivariate analysis, interaction among rapid
      transit, prior abdomen operation and large small-bowel volume (p = 0.019) were
      noted for early-onset diarrhoea. Further subgroup analysis revealed that rapid
      transit (p = 0.046) was a significant factor in patients with both prior
      abdominal operation and large small-bowel volume. The incidence of early-onset
      diarrhoea was as high as 40% in this particular group. Patients experiencing
      early-onset diarrhoea had a higher incidence of moderate to severe diarrhoea
      (65%) than those without early-onset diarrhoea (23%) (p<0.001). In multivariate
      analysis, early-onset diarrhoea was the only factor of moderate to severe
      diarrhoea (p = 0.001). In conclusion, rapid small-bowel transit may be
      predisposed to early-onset diarrhoea during pelvic radiotherapy in patients with
      both prior abdominal operations and large small-bowel volume. Early-onset
      diarrhoea is considered as a predictive factor of diarrhoea of a higher grade.

PMID- 16632624
TI  - Optical density variations in CT films and their effect on image quality.
AB  - It was recently reported that optical density (OD) variations were observed in CT
      films printed with a laser camera, depending on the printing format and the frame
      position within the film. The purpose of the present study was to investigate if
      these variations are common to both laser and dry-film printers and if the
      different OD settings along with day-to-day and frame-to-frame variations may
      affect the image quality. Eight laser and five dry-film printers installed at 12
      different CT facilities were tested. For each one, the SMPTE test pattern was
      printed on all frames of a film using the same printing format. The ODs of the
      0%, 10%, 40% and 70% patches of the 11-step greyscale of the SMPTE patterns were
      measured with a densitometer in all frames, while all films were examined on a
      viewing box to assess subjectively the image quality by visual inspection of the
      test pattern. A wide range of OD settings and variations were recorded. Frame-to
      frame variations in the same film of up to 0.19, 0.15 and 0.21 OD, were observed
      for contrast index (CI, the OD difference of patches 10% and 70%), speed index
      (SI, the OD of patch 40%) and maximum OD (OD(max), the OD of patch 0%),
      respectively. The variations were not always of the same magnitude, nor always
      followed the same pattern, even for printers of the same model. Considering all
      films and frames, the CI ranged from 1.26 to 1.74, the SI from 0.68 to 1.43 and
      the OD(max) from 2.5 to 3.11 OD, well beyond the proposed settings and tolerances
      of 1.55+/-0.15, 1.15+/-0.1 and 2.45+/-0.1 given in the literature for CI, SI and
      OD(max), respectively. Despite these large differences, the various problems that
      were identified in image quality from the visual inspection of the films could
      not be directly attributed to OD settings, as films with similar CI, SI and
      OD(max) presented quite different image quality levels. Therefore, for routine
      quality control, thorough visual inspection of the SMPTE test pattern provides
      all the necessary information about the imaging chain status.

PMID- 16632625
TI  - Short communication: assessment of environmental disturbances to the static
      magnetic field in magnetic resonance installations.
AB  - The static magnetic field of MRI scanners can be affected by environmental
      factors. Magnetic resonance spectroscopy and functional imaging with single-shot
      echo-planar imaging (EPI) are particularly vulnerable to the movement of lifts,
      vehicles, trains and other large metallic masses in the vicinity. This work
      investigates the sensitivity of two different imaging techniques to assess
      disturbances of the static magnetic field: (i) phase changes in gradient-echo
      images of a uniform test object; and (ii) image displacement along the phase
      encoding direction in single-shot EPI images. For the latter a hexane sample was
      used, and the separation between CH2 and CH3 signals was taken as a reference.
      Both techniques were evaluated in a site known to be free of any significant
      environmental disturbances and validated by inducing a magnetic field
      disturbance. Both techniques provide valuable information in acceptance tests,
      allowing MRI users to evaluate and manage the environmental conditions
      surrounding a scanner. The single-shot EPI technique was found to be highly
      sensitive, being expected to detect magnetic field fluctuations down to 0.005
      parts per million (ppm). The phase images method was found to be less sensitive
      (0.02 ppm) but is more easily available. The single-shot EPI technique was used
      in acceptance tests and environmental disturbances to the magnetic field of the
      order of 0.04 ppm were measured at the isocentre on two separate occasions.

PMID- 16632626
TI  - Short communication: an investigation of search pattern extent in the threshold
      contrast detection task.
AB  - The threshold contrast-detail diameter test is used as a semi-quantitative
      measure of image quality in radiology. This observation task is called "signal
      known exactly/background known exactly" because the signals are usually low
      contrast disks in known positions, and the background is uniform except for noise
      fluctuations. The performance of the observer undertaking this task can to some
      extent be predicted from knowledge of the noise power in the image background,
      and adoption of the assumption that the noise is sampled through an aperture of
      the same area as the test feature being observed. In order to extend this
      approach to optimization of clinical images, the effect of the cluttered
      anatomical background on the detection task must be quantified. To study the
      effect on detection of nearby structure, a series of contrast-detail tests was
      carried out using a progressively restricted background area of Gaussian noise,
      and a range of object diameters. It was found that the observer's ability to
      detect low contrast objects is progressively reduced as the area of the search
      area is reduced, the difficulty of the task increasing rapidly as the diameter of
      the restricted search area falls to less than twice that of the target disk. The
      results suggest the presence of a search pattern that scales in proportion with
      the size of the test feature.

PMID- 16632627
TI  - Short communication: imaging pulmonary embolism in pregnancy: what is the most
      appropriate imaging protocol?
AB  - Pulmonary embolism is the leading cause of death in pregnancy. Despite the
      difficulties in clinical diagnosis and the concerns regarding radiation of the
      fetus, the British Thoracic Society guidelines for imaging pulmonary embolism do
      not specifically address the issue of imaging for pulmonary embolism in this
      group. This communication discusses the difficulties of diagnosis and imaging
      pulmonary embolism in pregnancy and proposes a suitable imaging protocol.
      Clinical exclusion of patients from further imaging is recommended if the patient
      has a low pre-test probability of pulmonary embolism and a normal d-dimer. It is
      advised that all remaining patients undergo bilateral leg Doppler assessment. If
      this test is positive, the patient should be treated for pulmonary embolism; if
      negative, all patients should be referred for CT pulmonary angiography. Ideally,
      informed consent should be obtained prior to CT scanning. All neonates exposed to
      iodinated contrast in utero should have their thyroid function tested in the
      first week of life due to the theoretical risk of contrast induced
      hypothyroidism.

PMID- 16632628
TI  - Case report: primary subcutaneous sacrococcygeal ependymoma: a case report and
      review of the literature.
AB  - Extraspinal ependymomas are rare. The majority occur in the sacrococcygeal
      region. The subcutaneous variety accounts for approximately two thirds of cases,
      which are commonly misdiagnosed as a pilonidal cyst or sinus. Treatment is
      complete surgical resection. The role of coccygectomy is controversial. Adjuvant
      radiotherapy is of benefit to those with an incompletely excised tumour. Up to
      20% metastasise, chiefly to the inguinal lymph glands, but pulmonary metastases
      are also reported. Palliative chemotherapy has not been shown to be of any
      benefit. Long term follow-up is important as metastases can occur up to 20 years
      after initial presentation. We report a 37-year-old woman with a subcutaneous
      sacrococcygeal ependymoma with iliac lymph nodal metastasis at presentation.

PMID- 16632629
TI  - Dose distribution to the mediastinum and heart.

PMID- 16632630
TI  - Case of the month: a catastrophic complication.

PMID- 16632631
TI  - "Hot stuff": bronchial thermoplasty for asthma.

PMID- 16632632
TI  - Assessing tuberculosis transmission and virulence: the vanishing tuberculin skin
      test.

PMID- 16632633
TI  - Update in cystic fibrosis 2005.

PMID- 16632634
TI  - Update in environmental and occupational medicine 2005.

PMID- 16632635
TI  - Human embryonic stem cell research.

PMID- 16632636
TI  - Pressure increase due to hydrostatic pressure of perfluorocarbon.

PMID- 16632637
TI  - Cystic fibrosis disease-specific centiles in 2000 and 2005.

PMID- 16632638
TI  - Exhaled breath condensate pH.

PMID- 16632639
TI  - Prolonged reduction of leukocyte membrane-associated Dectin-1 levels following
      beta-glucan administration.
AB  - Dectin-1 is the primary pattern recognition receptor for fungal glucans. Dectin-1
      mediates the internalization and biological response to glucans. We examined the
      effect of i.v. or i.p. glucan phosphate (GP) administration on Dectin-1 membrane
      expression in murine peripheral blood leukocytes, splenocytes, bone marrow, and
      peritoneal cells from 3 h to 10 days after injection. Circulating leukocytes were
      also examined for uptake and internalization of glucans from the blood.
      Fluorescent-labeled GP was taken up from the systemic circulation by circulating
      peripheral leukocytes, splenocytes, and peritoneal cells. Following
      internalization, glucan colocalized with Dectin-1 in an intracellular vesicle. A
      single parenteral injection of GP resulted in a significant reduction
      (approximately 33-85%) in peripheral leukocyte membrane-associated Dectin-1
      positivity that lasted for up to 7 days. The loss of leukocyte membrane
      associated Dectin-1 after GP administration was primarily due to decreased levels
      of Dectin-1 on neutrophil and monocyte membranes with no significant changes in
      the percentage of neutrophils or monocytes circulating in the blood.
      Administration of control carbohydrate polymers, i.e., mannan or pullulan, which
      are not ligands for Dectin-1, did not decrease Dectin-1 leukocyte positivity,
      indicating that the effect on Dectin-1 is specific to glucans. In fact, mannan
      administration increased leukocyte Dectin-1 positivity, thus demonstrating a
      differential effect on leukocyte Dectin-1, compared with GP. We conclude that
      systemic administration of GP has a specific and prolonged effect on loss of
      leukocyte membrane Dectin-1 positivity. These data may have important
      implications for developing dosing regimens for immunomodulatory carbohydrates.

PMID- 16632640
TI  - Antitumor activity of sphingosine kinase inhibitors.
AB  - Sphingosine kinase (SK) is an oncogenic sphingolipid-metabolizing enzyme that
      catalyzes the formation of the mitogenic second messenger sphingosine-1-phosphate
      (S1P) at the expense of proapoptotic ceramide. Thus, SK is an attractive target
      for cancer therapy because blockage of S1P formation leads to inhibition of
      proliferation, as well as the induction of apoptosis in cancer cells. We have
      recently identified novel SK inhibitors with nanomolar to low micromolar
      potencies toward recombinant human SK. This study describes the continuing
      analysis of these inhibitors through in vitro and in vivo experiments. All three
      structurally diverse SK inhibitors tested showed antitumor activity in mice
      without exhibiting toxicity. Blood and tumor inhibitor concentrations exceeded in
      vitro potency levels. Cell signaling analyses in vitro revealed mixed inhibition
      of mitogen-activated protein kinase kinase and Akt phosphorylation by the SK
      inhibitors. Importantly, 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI
      II) is orally bioavailable, detected in the blood for at least 8 h, and showed a
      significant inhibition of tumor growth in mice. These compounds are the first
      examples of nonlipid selective inhibitors of SK with in vivo antitumor activity
      and provide leads for further development of inhibitors of this important
      molecular target.

PMID- 16632641
TI  - Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell
      cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase
      mediated phosphorylation at serine 15 in vitro and in vivo.
AB  - This study first investigates the anticancer effect of plumbagin (5-hydroxy-2
      methyl-1,4-naphthoquinone) in human nonsmall cell lung cancer cells, A549.
      Plumbagin has exhibited effective cell growth inhibition by inducing cancer cells
      to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated
      with increased levels of p21 and reduced amounts of cyclinB1, Cdc2, and Cdc25C.
      Plumbagin treatment also enhanced the levels of inactivated phosphorylated Cdc2
      and Cdc25C. Blockade of p53 activity by dominant-negative p53 transfection
      partially decreased plumbagin-induced apoptosis and G2/M arrest, suggesting it
      might be operated by p53-dependent and independent pathway. Plumbagin treatment
      triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2
      ratios, resulting in mitochondrial membrane potential loss, cytochrome c release,
      and caspase-9 activation. We also found that c-Jun NH2-terminal kinase (JNK) is a
      critical mediator in plumbagin-induced cell growth inhibition. Activation of JNK
      by plumbagin phosphorylated p53 at serine 15, resulting in increased stability of
      p53 by decreasing p53 and MDM2 interaction. SP600125 (anthra [1,9-cd]pyrazol
      6(2H)-one-1,9-pyrazoloanthrone), a specific inhibitor of JNK, significantly
      decreased apoptosis by inhibiting the phosphorylation of p53 (serine 15) and
      subsequently increased the interaction of p53 and MDM2. SP6000125 also inhibited
      the phosphorylation of Bcl-2 (Ser70) induced by plumbagin. Further investigation
      revealed that plumbagin's inhibition of cell growth effect was also evident in a
      nude mice model. Taken together, these results suggest a critical role for JNK
      and p53 in plumbagin-induced G2/M arrest and apoptosis of human nonsmall cell
      lung cancer cells.

PMID- 16632642
TI  - Angularly nonspecific response suppression in rat barrel cortex.
AB  - Response modulation by prior sensory stimulation is a common property of cortical
      neurons. The degree to which effects are specific to the adapting stimulus
      provides insights into properties of the underlying circuitry. Here, we examined
      the effects of an adapting whisker deflection's angle on the angular tuning of
      layer IV barrel neurons and their major input source, thalamic barreloid neurons.
      In both barrel regular-spike units (RSUs) and fast-spike units (FSUs), presumed
      excitatory and inhibitory neurons, prior whisker deflections suppressed
      subsequent test deflections in a largely angularly nonspecific manner, that is,
      adaptation in one direction reduced responses for test deflections of all angles.
      FSUs were poorly tuned for deflection angle and remained so after adaptation. In
      adapted RSUs, responses to suboptimal directions were suppressed most and angular
      preferences remained constant; tuning therefore became sharper. Adaptation
      effects in RSUs and FSUs do not appear to reflect corresponding changes in
      thalamic neurons. The angularly nonspecific suppression of barrel neurons is
      likely mediated by local intrabarrel suppressive interactions, such as broadly
      tuned inhibition and/or short-term synaptic depression of excitatory connections.
      The dominance of angularly nonspecific suppression suggests that barrel neurons
      interact largely in an angularly nonspecific manner to reinforce stimulus
      preferences encoded by their synchronously firing thalamic inputs.

PMID- 16632643
TI  - Comparative genomics of Brassica oleracea and Arabidopsis thaliana reveal gene
      loss, fragmentation, and dispersal after polyploidy.
AB  - We sequenced 2.2 Mb representing triplicated genome segments of Brassica
      oleracea, which are each paralogous with one another and homologous with a
      segmentally duplicated region of the Arabidopsis thaliana genome. Sequence
      annotation identified 177 conserved collinear genes in the B. oleracea genome
      segments. Analysis of synonymous base substitution rates indicated that the
      triplicated Brassica genome segments diverged from a common ancestor soon after
      divergence of the Arabidopsis and Brassica lineages. This conclusion was
      corroborated by phylogenetic analysis of protein families. Using A. thaliana as
      an outgroup, 35% of the genes inferred to be present when genome triplication
      occurred in the Brassica lineage have been lost, most likely via a deletion
      mechanism, in an interspersed pattern. Genes encoding proteins involved in signal
      transduction or transcription were not found to be significantly more extensively
      retained than those encoding proteins classified with other functions, but
      putative proteins predicted in the A. thaliana genome were underrepresented in B.
      oleracea. We identified one example of gene loss from the Arabidopsis lineage. We
      found evidence for the frequent insertion of gene fragments of nuclear genomic
      origin and identified four apparently intact genes in noncollinear positions in
      the B. oleracea and A. thaliana genomes.

PMID- 16632644
TI  - Sequence-level analysis of the diploidization process in the triplicated
      FLOWERING LOCUS C region of Brassica rapa.
AB  - Strong evidence exists for polyploidy having occurred during the evolution of the
      tribe Brassiceae. We show evidence for the dynamic and ongoing diploidization
      process by comparative analysis of the sequences of four paralogous Brassica rapa
      BAC clones and the homologous 124-kb segment of Arabidopsis thaliana chromosome
      5. We estimated the times since divergence of the paralogous and homologous
      lineages. The three paralogous subgenomes of B. rapa triplicated 13 to 17 million
      years ago (MYA), very soon after the Arabidopsis and Brassica divergence occurred
      at 17 to 18 MYA. In addition, a pair of BACs represents a more recent segmental
      duplication, which occurred approximately 0.8 MYA, and provides an exception to
      the general expectation of three paralogous segments within the B. rapa genome.
      The Brassica genome segments show extensive interspersed gene loss relative to
      the inferred structure of the ancestral genome, whereas the Arabidopsis genome
      segment appears little changed. Representatives of all 32 genes in the
      Arabidopsis genome segment are represented in Brassica, but the hexaploid
      complement of 96 has been reduced to 54 in the three subgenomes, with compression
      of the genomic region lengths they occupy to between 52 and 110 kb. The gene
      content of the recently duplicated B. rapa genome segments is identical, but
      intergenic sequences differ.

PMID- 16632645
TI  - Class B GPCRs: a hidden agonist within?
AB  - Class B G protein-coupled receptors (GPCRs) regulate a wide range of endocrine
      and neuroendocrine functions and are endogenously stimulated by moderately large
      peptide hormones. Current evidence suggests that the carboxyl termini of cognate
      peptides bind to the amino terminus of their G protein-coupled receptors (GPCRs)
      and that the peptides' amino terminal segments then dock to the heptahelical
      receptor portion to induce signaling. In this issue of Molecular Pharmacology,
      Dong et al. (p. 206) propose an alternative model of ligand-induced class B GPCR
      activation. Based primarily on studies with the secretin receptor, a prototype
      class B family member, they provide evidence that the endogenous peptide hormone
      does not function as an activator per se. Instead, this hormone (secretin)
      exposes a hidden, built-in agonist epitope that is present within the amino
      terminus of its target GPCR. Isolated oligopeptide fragments containing this
      epitope act as full agonists on the secretin receptor despite their lack of amino
      acid homology with the secretin hormone. These nonconventional agonists can be
      minimized to tripeptide molecules and still maintain biological activity. The
      study to be discussed introduces a novel paradigm of class B GPCR function, and
      may facilitate the elusive goal of finding small molecule agonist drugs for this
      therapeutically attractive group of receptors.

PMID- 16632646
TI  - Modification and uptake of a cisplatin carbonato complex by Jurkat cells.
AB  - The interactions of Jurkat cells with cisplatin, cis-[Pt(15NH3)2Cl2]1, are
      studied using 1H-15N heteronuclear single quantum coherence (HSQC) NMR and
      inductively coupled plasma mass spectrometry. We show that Jurkat cells in
      culture rapidly modify the monocarbonato complex cis-[Pt(15NH3)2(CO3)Cl]- (4), a
      cisplatin species that forms in culture media and probably also in blood.
      Analysis of the HSQC NMR peak intensity for 4 in the presence of different
      numbers of Jurkat cells reveals that each cell is capable of modifying 0.0028
      pmol of 4 within approximately 0.6 h. The amounts of platinum taken up by the
      cell, weakly bound to the cell surface, remaining in the culture medium, and
      bound to genomic DNA were measured as functions of time of exposure to different
      concentrations of drug. The results show that most of the 4 that has been
      modified by the cells remains in the culture medium as a substance of molecular
      mass <3 kDa, which is HSQC NMR silent, and is not taken up by the cell. These
      results are consistent with a hitherto undocumented extracellular detoxification
      mechanism in which the cells rapidly modify 4, which is present in the culture
      medium, so it cannot bind to the cell. Because there is only a slow decrease in
      the amount of unmodified 4 remaining in the culture medium after 1 h, -1.1 +/-
      0.4 microM h(-1), the cells subsequently lose their ability to modify 4. These
      observations have important implications for the mechanism of action of
      cisplatin.

PMID- 16632647
TI  - Images in neonatal medicine. Fatal newborn head enlargement: high resolution
      magnetic resonance imaging at 4.7 T.

PMID- 16632648
TI  - Pathways of neonatal stroke and subclavian steal syndrome.
AB  - Neonatal stroke may occur silently. Identification of potential embolic pathways
      unique to the neonate is important when investigating the aetiology of infarction
      and arterial occlusion, and preventing further episodes. This is a case report of
      an infant with venous thrombus embolising across the foramen ovale causing
      cerebral infarction and subclavian artery steal syndrome, without neurological
      signs.

PMID- 16632649
TI  - Newer approaches to the diagnosis of early onset neonatal sepsis.
AB  - Accurate and timely diagnosis of early onset neonatal sepsis remains challenging
      to the clinician and the laboratory. A test with a rapid turnaround time with
      100% sensitivity, rather than high specificity, which allows accurate diagnosis
      and appropriate antimicrobial treatment or which allows antibiotics to be safely
      withheld in non-infected infants, is desirable. Many potential markers (acute
      phase reactants, cell surface markers, cytokines) are not routinely available to
      the laboratory, and most likely combinations of markers will ensure greater
      diagnostic accuracy. In the future, molecular biology techniques offer the
      prospect of rapid identification of both pathogens and antimicrobial resistance
      markers.

PMID- 16632650
TI  - Which inotrope for which baby?
AB  - While we know a lot about blood pressure (BP) responses to various inotropes and
      a bit about systemic and organ blood flow responses, we know almost nothing about
      how different inotropes affect clinical outcomes. Low systemic blood flow (SBF)
      is common in the first 24 h after birth in very preterm babies (and more mature
      babies with severe respiratory problems) and is not always reflected by low BP.
      The causes of this low SBF are complex but may relate to maladaptation to high
      extrauterine systemic (and sometimes pulmonary) vascular resistance. After day 1,
      hypotensive babies are more likely to have normal or high SBF reflecting
      vasodilatation. Empirically, inotropes that reduce afterload (such as dobutamine)
      may be more appropriate in the transitional period, while those with more
      vasoconstrictor actions (such as dopamine) may be more appropriate later on.
      Defining the haemodynamic in an individual baby needs both BP and
      echocardiographic measures of SBF. Research in this area needs to move beyond
      just demonstrating changes in physiological variables to showing improvements in
      important clinical outcomes.

PMID- 16632651
TI  - Outcome of extreme prematurity: as information increases so do the dilemmas.
AB  - Application of technology in neonatal intensive care has been very successful in
      reducing mortality, particularly in extremely low birthweight infants. As
      survival has improved, the need for accurate studies of long term outcome has
      increased. This need has been met by studies that are larger, more inclusive, and
      address a wider variety of later outcomes. Rather than a comprehensive
      quantitative review of these studies, this article uses a smaller number of
      studies that focus on infants of borderline viability, to illustrate current
      dilemmas and challenges in interpretation, and the actions, both individual and
      societal, that may be prompted by these interpretations.

PMID- 16632652
TI  - Minimising ventilator induced lung injury in preterm infants.
AB  - Ventilator induced lung injury continues to occur at an unacceptably high rate,
      which is inversely related to gestational age. Although the "new BPD" may not be
      entirely avoidable in the extremely premature infant, recognition of risk factors
      and adoption of an appropriate ventilatory strategy, along with continuous real
      time monitoring, may help to minimise lung damage. This paper will review the
      pathogenesis of ventilator induced lung injury and strategies that may mitigate
      it.

PMID- 16632653
TI  - Adolphe Pinard (1844-1934) of Paris and intrauterine paediatric care.
AB  - Pinard was a pioneer of modern perinatal care. His provision of social care to
      deprived pregnant women progressed to a recognition of the value of medical care
      of mother and baby before as well as after birth. The creation of antenatal
      departments and wards in maternity hospitals followed. He also established
      abdominal obstetric palpation on sound principles.

PMID- 16632654
TI  - Pooling of trials is not appropriate in the case of heterogeneity.

PMID- 16632655
TI  - Nasal nitric oxide to diagnose primary ciliary dyskinesia in newborns.

PMID- 16632656
TI  - The pressure is on! The danger of a broken blow off valve on a bag valve mask.

PMID- 16632657
TI  - Not all osmolality is created equal.

PMID- 16632658
TI  - Asphyxia or just hypoxia?

PMID- 16632660
TI  - Is limited computed tomography the future for imaging the lungs of children with
      cystic fibrosis?

PMID- 16632661
TI  - Who should manage infants and young children with food induced symptoms?

PMID- 16632662
TI  - Acute haemorrhagic oedema of infancy.

PMID- 16632663
TI  - Relationships between paediatricians and infant formula milk companies.

PMID- 16632664
TI  - Phytophotodermatitis.

PMID- 16632665
TI  - Relationships between paediatricians and infant milk formula companies.

PMID- 16632668
TI  - An Eiffel penetrating head injury.

PMID- 16632669
TI  - Biliary hypoplasia in Williams syndrome.
AB  - Neonatal hepatitis and biliary hypoplasia are not recognised features of Williams
      syndrome. A case of Williams syndrome, presenting with neonatal conjugated
      hyperbilirubinaemia leading to an initial misdiagnosis is reported.

PMID- 16632670
TI  - Pneumothorax after a roller coaster ride.

PMID- 16632671
TI  - Highlights in asthma 2005.
AB  - It is usual at the end of a year for top tens to feature large in our collective
      consciousness. These inevitably include the occasional controversial selection
      and without fail will overlook a number of gems, whether in the field of
      literature, art, or science. The approaches to such compilations include personal
      selections, convening expert committees through to letting the market decide.
      However, it is well recognised that experts can be wrong and markets distorted. A
      novel approach to identifying the key publications in the field of medicine,
      Faculty of 1000 Medicine (http://www.f1000medicine.com), uses faculty evaluations
      to assign ratings to published papers within topics and categories, bringing a
      flavour of the dynamism of post hoc peer review to biological sciences that
      exists in other fields of scholarship. Archives of Disease in Childhood has also
      developed a market led system of peer evaluation through its web based top ten
      most read articles feature.

PMID- 16632672
TI  - Inflammatory bowel disease.
AB  - Twenty five per cent of inflammatory bowel disease presents in childhood. Growth
      and nutrition are key issues in the management with the aim of treatment being to
      induce and then maintain disease remission with minimal side effects. Only 25% of
      Crohn's disease presents with the classic triad of abdominal pain, weight loss,
      and diarrhoea. Most children with ulcerative colitis have blood in the stool at
      presentation. Inflammatory markers are usually although not invariably raised at
      presentation (particularly in Crohn's disease). Full investigation includes upper
      gastrointestinal endoscopy and ileocolonoscopy. Treatment requires
      multidisciplinary input as part of a clinical network led by a paediatrician with
      special expertise in the management of the condition.

PMID- 16632673
TI  - Growing up with idiopathic short stature: psychosocial development and hormone
      treatment; a critical review.
AB  - To facilitate decisions on interventions in medically referred children with
      idiopathic short stature, the research on psychosocial functioning of these
      children, possible risk and protective factors influencing adaptation, and
      effects of hormone treatment were reviewed. Parents ranked the behaviour of their
      children on average between normal and below normal. The magnitude of these
      deviations varied from small to large. Little is known about the children's self
      perceived psychosocial functioning. Some risk factors were found: being teased,
      being juvenilised, being a boy, having a younger but taller sibling, low
      intelligence, and low socioeconomic status. There have been few studies on the
      impact of protective factors including temperament, coping strategies, and social
      support. On average, hormone treatment did not improve psychosocial functioning.
      The research shows the advantages and disadvantages of hormone treatment that
      must be considered when choosing a suitable intervention. It is suggested that
      psychosocial adjustment can be improved by focusing on factors other than height
      alone.

PMID- 16632674
TI  - Cardiac disease and Rett syndrome.
AB  - Rett syndrome (RS) is a neurodevelopmental disease,1 affecting approximately 1 in
      10 000-15 000 females. Clinical severity of RS may vary with increasing age,
      following a four stage model.

PMID- 16632675
TI  - Selecting doctors for postgraduate training in paediatrics using a competency
      based assessment centre.
AB  - The design and implementation of an assessment centre in the South Yorkshire and
      South Humberside deanery for selecting doctors into postgraduate training in
      paediatric medicine is described. Eleven competency domains were identified in
      the job analysis. An assessment centre comprising of four exercises was
      implemented to assess candidates. There were modest relationships between
      candidates' performance on the various assessment centre exercises. Outcomes
      based on interview performance were related to, but not the same as, outcomes
      based on the combined results of the three other assessment centre exercises.
      Candidates perceived the assessment centre to be a fair selection method. It is
      concluded that an assessment centre approach to SHO recruitment is feasible and
      provides a greater breadth and depth of information about candidates than does a
      structured interview.

PMID- 16632676
TI  - Pitfalls in the use of adenosine.

PMID- 16632677
TI  - Antenatal steroids and neonatal renal function.

PMID- 16632678
TI  - Septic peripheral embolization from Haemophilus parainfluenzae endocarditis.

PMID- 16632679
TI  - Personal fulfillment and professional excellence: Dorothy Reed Mendenhall,
      pathologist and Children's Bureau investigator.

PMID- 16632680
TI  - Endocrine regulation of HOX genes.
AB  - Hox genes have a well-characterized role in embryonic development, where they
      determine identity along the anteroposterior body axis. Hox genes are expressed
      not only during embryogenesis but also in the adult, where they are necessary for
      functional differentiation. Despite the known function of these genes as
      transcription factors, few regulatory mechanisms that drive Hox expression are
      known. Recently, several hormones and their cognate receptors have been shown to
      regulate Hox gene expression and thereby mediate development in the embryo as
      well as functional differentiation in the adult organism. Estradiol,
      progesterone, testosterone, retinoic acid, and vitamin D have been shown to
      regulate Hox gene expression. In the embryo, the endocrine system directs axial
      Hox gene expression; aberrant Hox gene expression due to exposure to endocrine
      disruptors contributes to the teratogenicity of these compounds. In the adult,
      endocrine regulation of Hox genes is necessary to enable such diverse functions
      as hematopoiesis and reproduction; endocrinopathies can result in dysregulated
      HOX gene expression affecting physiology. By regulating HOX genes, hormonal
      signals utilize a conserved mechanism that allows generation of structural and
      functional diversity in both developing and adult tissues. This review discusses
      endocrine Hox regulation and its impact on physiology and human pathology.

PMID- 16632681
TI  - Radiofrequency ablation: the future is now.

PMID- 16632682
TI  - Diaphragmatic hernia after radiofrequency ablation therapy for hepatocellular
      carcinoma.

PMID- 16632683
TI  - Radiofrequency ablation of osteoid osteoma with cooled probes and impedance
      control energy delivery.
AB  - OBJECTIVE: Our objective was to evaluate the efficacy of percutaneous
      radiofrequency ablation of osteoid osteoma with cooled radiofrequency probes and
      impedance control energy delivery from a 200-W generator. We also compared the
      outcome to published data for therapy with a 5-mm noncooled probe and temperature
      controlled short-duration therapy protocols. SUBJECTS AND METHODS: Radiofrequency
      ablation was performed on 11 patients with a clinical and radiologic diagnosis of
      osteoid osteoma. A cooled radiofrequency probe was introduced into the lesion
      under CT guidance. Twelve minutes of radiofrequency energy was delivered from a
      200-W generator under impedance control. Postprocedural pain, function, and
      satisfaction were evaluated by means of an interview and questionnaire. RESULTS:
      All procedures were technically successful. No serious complication occurred.
      Postoperative pain was scored at a mean of 6.9 +/- 3.06 (95% confidence interval)
      on a numeric rating scale. Postoperative pain was rated as similar to night pain.
      By 1 week after therapy, all patients had resolution of pain and returned to
      normal activity. There was no recurrence during the follow-up period (range, 6-27
      months; mean, 14.4 months). Patients rated their satisfaction as high.
      CONCLUSION: Radiofrequency ablation of osteoid osteoma with a high-energy
      delivery technique is safe and has a high success rate. When compared with
      patients in a published series using 5-mm probes and manual energy control from
      lower-output generators, our cohort showed increased postoperative pain scores
      and an increased interval to symptom resolution.

PMID- 16632684
TI  - Unintended thermal injuries from radiofrequency ablation: protection with 5%
      dextrose in water.
AB  - OBJECTIVE: Radiofrequency ablation of hepatic tumors can lead to thermal injury
      of surrounding structures. Both saline and 5% dextrose in water (D5) have been
      used to displace these surrounding structures before radiofrequency ablation. The
      purpose of this study was to determine the relative effectiveness of these two
      fluids for protecting the diaphragm and lung during radiofrequency ablation.
      MATERIALS AND METHODS: Ten female domestic swine (mean weight, 45 kg) underwent
      radiofrequency ablation at open surgery. Group 1 (n = 12 lesions) was pretreated
      with peritoneal D5 before radiofrequency ablation. Group 2 (n = 11 lesions) was
      pretreated with peritoneal 0.9% saline. A 2.7-mm spacer was placed between the
      liver surface and diaphragm in groups 1 and 2. Group 3 (n = seven lesions) served
      as a control group with no pretreatment regimen. Group 4, an additional control
      group (n = eight lesions), consisted of animals pretreated with D5 in which a
      larger spacer was used. After radiofrequency ablation, the animals were
      sacrificed and the liver, diaphragm, and lung were removed. The extent of thermal
      injury to the surface of each organ was recorded. RESULTS: The animals in the D5
      and saline pretreatment groups experienced fewer diaphragm injuries than the
      control animals (D5, p = 0.02). The smallest lesions in the lung and diaphragm
      were in the D5 group, followed by the saline and control groups (diaphragm, p =
      0.0001; lung, p = 0.13). Diaphragm lesions were significantly smaller in the D5
      and saline groups than in the control group (p = 0.0001 and 0.01, respectively).
      CONCLUSION: Instillation of D5 into the peritoneal cavity before hepatic
      radiofrequency ablation decreases the risk and severity of diaphragm and lung
      injuries compared with no pretreatment or pretreatment with 0.9% saline in this
      animal model. Pretreatment with D5 may increase both the safety of and the number
      of patients eligible for treatment with thermal therapies.

PMID- 16632685
TI  - Virtual sonographic radiofrequency ablation of hepatocellular carcinoma
      visualized on CT but not on conventional sonography.
AB  - OBJECTIVE: Some nodules cannot be visualized clearly on conventional sonography
      but can be visualized on CT. In the present study, we evaluated the usefulness of
      real-time percutaneous ablation therapy under virtual sonographic guidance for
      these nodules. SUBJECTS AND METHODS: In vitro experiments were performed with
      gelatin gel to evaluate the accuracy of virtual sonography. We also studied 50
      patients with 58 hepatocellular carcinoma nodules, of whom 18 patients (21
      nodules) underwent radiofrequency ablation by virtual sonography. This was the
      initial treatment for seven of these patients and an additional treatment for 11
      patients. Thirty-two patients (37 nodules) received radiofrequency ablation
      without virtual imaging. The patients receiving standard radiofrequency ablation
      were retrospectively selected as the historical control group under the same
      conditions as the study group. RESULTS: The in vitro gelatin gel study revealed
      that all punctures had been performed accurately. In both the initial-treatment
      group and the additional-treatment group, the mean number of treatments with
      virtual sonography was significantly lower than that without virtual sonography
      (p = 0.003 for both groups). The rates of local recurrence and complications did
      not differ significantly between the two groups. CONCLUSION: In the treatment of
      nodules not depicted on sonography, radiofrequency ablation assisted by virtual
      sonography is an efficacious alternative.

PMID- 16632686
TI  - Radiofrequency ablation of hepatocellular carcinoma in patients with
      decompensated cirrhosis: evaluation of therapeutic efficacy and safety.
AB  - OBJECTIVE: Our objective was to determine the therapeutic efficacy and safety of
      radiofrequency ablation in the treatment of hepatocellular carcinoma (HCC) in
      patients with decompensated cirrhosis. SUBJECTS AND METHODS: Nineteen patients
      with 26 HCC nodules (range, 0.8-5 cm; mean, 1.96 cm) and decompensated liver
      cirrhosis (mean Child score, 10.7) were treated with radiofrequency ablation
      using cooled-tip electrodes and a 200-W generator. Radiofrequency ablation was
      performed under the guidance of sonography or CT. Procedure-related
      complications, therapeutic efficacy, each patient's survival, changes in blood
      test results--that is, serum aminotransferase and bilirubin--and changes in the
      Child score before and after ablation therapy were analyzed. To assess the
      therapeutic response of the tumor to radiofrequency ablation, we performed
      contrast-enhanced CT after the procedure and during follow-up. RESULTS: Complete
      necrosis without marginal recurrence at the 6-month follow-up was attained in 23
      lesions (88.5%). During follow-up (mean, 13.3 months), one patient experienced a
      remote tumor recurrence in the liver. The median survival time was 12.0 +/- 1.7
      months. Two patients died of liver failure--one at 2 months and one at 4 months
      after treatment. The other patients were followed for at least 6 months (range, 6
      28 months; mean, 12 months). The first and second weeks after therapy, the serum
      aminotransferase and bilirubin levels were significantly higher than were
      pretreatment levels (p < 0.05). However, 3 weeks after therapy, those figures
      were nearly restored to the pretreatment levels. The mean Child scores 3 weeks
      after radiofrequency ablation (10.8) were similar to those before treatment
      (10.7). CONCLUSION: Radiofrequency ablation can be used selectively for treatment
      of HCC in patients with decompensated cirrhosis but has the potential to
      aggravate the preexisting hepatic dysfunction.

PMID- 16632687
TI  - Percutaneous radiofrequency ablation therapy of hepatocellular carcinoma using
      multitined expandable electrodes: comparison of subcapsular and nonsubcapsular
      tumors.
AB  - OBJECTIVE: Our objective was to compare the prognosis of subcapsular and
      nonsubcapsular hepatocellular carcinoma after percutaneous radiofrequency
      ablation using multitined expandable electrodes. MATERIALS AND METHODS: Some
      controversies exist about the clinical usefulness of percutaneous radiofrequency
      ablation of subcapsular hepatocellular carcinoma. Twenty-eight patients underwent
      percutaneous radiofrequency ablation of 43 hepatocellular carcinomas using
      multitined expandable electrodes. Twelve tumors were subcapsular and 31 were
      nonsubcapsular. We attempted to use normal liver as a pathway to the tumor when
      possible. Tumor size ranged from 1.0 to 4.2 cm (mean, 1.8 cm). Median follow-up
      was 16 months. Initial ablation was considered to have been complete when no
      enhancement was seen in the region of the ablated lesion on 1-month follow-up CT
      or on follow-up CT performed immediately after repeated ablation. Initial
      complete ablation and local tumor progression rates were compared between
      subcapsular and nonsubcapsular tumors. Eleven patients had subcapsular tumors
      (group 1), whereas the other 17 patients did not have subcapsular tumors (group
      2). Major complication and mortality rates were compared between the two groups.
      RESULTS: No significant differences in initial complete ablation rate (100% vs
      96.7%, p = 1.000) or local tumor progression rate (0% vs 10.0%, p = 0.545) were
      found between subcapsular and nonsubcapsular tumors. No procedure-related major
      complication or mortality occurred. The overall 1- and 3-year survival rates were
      89.3% and 60.3%, respectively. CONCLUSION: The rates of local tumor progression
      and complications for radiofrequency ablation using multitined expandable
      electrodes for subcapsular hepatocellular carcinomas were comparable to those for
      nonsubcapsular hepatocellular carcinomas.

PMID- 16632688
TI  - Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy:
      therapeutic efficacy on early- and late-phase recurrence.
AB  - OBJECTIVE: Our objective was to assess the efficacy and safety of radiofrequency
      ablation of recurrent hepatocellular carcinoma (HCC) after hepatectomy and to
      compare the effects on early- and late-phase recurrence. SUBJECTS AND METHODS: We
      studied 41 patients with 76 recurrent HCC tumors (diameter range, 2.0-6.6 cm;
      mean, 3.8 +/- 1.3 [SD] cm) after hepatectomy who underwent sonography-guided
      percutaneous radiofrequency ablation in our hospital (recurrent-HCC group). The
      interval between surgery and recurrence ranged from 1 to 96 months (mean, 24.5
      months). These patients were divided into an early-recurrence group (20 patients
      with 41 recurrent HCC tumors) and a late-recurrence group (21 patients with 35
      recurrent HCC tumors). Early recurrence was defined as that occurring within 1
      year after surgery, and late recurrence was defined as that occurring after 1
      year. Another 116 patients with 172 primary HCC tumors (diameter range, 1.2-7.0
      cm; mean, 3.9 +/- 1.1 cm) treated by radiofrequency ablation were regarded as a
      control group. No other therapies were given before radiofrequency ablation in
      any group. Regular follow-up with enhanced CT was performed to evaluate the
      treatment results. Ablation was considered successful if no contrast enhancement
      was detected in the treated area on 1-month CT scans. Indexes including ablation
      success rate, local recurrence rate, distant recurrence rate, and survival were
      obtained for analysis and comparison. RESULTS: The ablation success rate, local
      recurrence rate, distant recurrence rate, and mean overall survival time of the
      recurrent-HCC group were 93.4% (71/76 tumors), 9.2% (7/76 tumors), 36.6% (15/41
      patients), and 30.9 +/- 3.7 months, respectively. The incidence of distant
      recurrence in the early-recurrence group was significantly higher than that in
      the late-recurrence group (55.0% vs 19.0%, p = 0.017). The early-recurrence group
      had a shorter overall survival than did the late-recurrence group (mean overall
      survival, 16.4 +/- 2.4 vs 42.9 +/- 4.4 months, p < 0.001) or the control group
      (16.4 +/- 2.4 vs 45.9 +/- 2.5 months, p < 0.001). The survival time of the late
      recurrence group was similar to that of the control group (42.9 +/- 4.4 vs 45.9
      +/- 2.5 months, p > 0.05). Serious hemorrhage after radiofrequency ablation
      occurred in one patient in the late-recurrence group and was controlled with
      conservative treatment. CONCLUSION: Radiofrequency ablation is generally
      effective and safe in treating recurrent HCC after hepatectomy and is more
      effective in late recurrence than in early recurrence.

PMID- 16632689
TI  - CT artifact introduced by radiofrequency ablation.

PMID- 16632690
TI  - Radiofrequency ablation of hepatocellular carcinoma: predicting success using
      contrast-enhanced sonography.
AB  - OBJECTIVE: This pilot study compared the utility of immediate postprocedural
      contrast-enhanced sonography with that of delayed enhanced sonography and CT or
      MRI in assessing the success of radiofrequency ablation of hepatocellular
      carcinoma. SUBJECTS AND METHODS: Twenty-two lesions (1.5-3.7 cm) were studied in
      19 patients. Enhanced sonography was performed before and within 1 hr after
      radiofrequency ablation. At routine 2-week follow-up CT or MRI, additional
      enhanced sonography was performed. The findings of preablation CT or MRI and
      enhanced sonography were compared with those of postprocedural and follow-up
      enhanced sonography by three radiologists experienced in these techniques. The
      reviewers were unaware of the follow-up CT or MRI results (reference standard).
      Technical adequacy, ablation zone targeting, and identification of residual
      disease were assessed by each reviewer, and the results were analyzed by
      consensus. RESULTS: One postprocedural sonographic study was considered
      technically inadequate. Postprocedural sonography predicted the follow-up CT or
      MRI results in 76% (16/21) of subjects (sensitivity, 88%; specificity, 40%;
      positive predictive value [PPV], 82%; negative predictive value, [NPV] 50%).
      Follow-up CT or MRI identified accurate targeting in 17 of 22 subjects. Follow-up
      sonography agreed with CT or MRI in 82% (18/22) of subjects (sensitivity, 88%;
      specificity, 67%; PPV, 88%; NPV, 67%). Postprocedural sonography predicted the
      follow-up CT or MRI results in 81% (17/21) of subjects (sensitivity, 40%;
      specificity, 94%; PPV, 66%; NPV, 83%). Follow-up CT or MRI detected residual
      disease in six subjects. Follow-up sonography agreed with CT or MRI in 91%
      (20/22) of subjects (sensitivity, 83%; specificity, 94%; PPV, 83%; NPV, 94%).
      CONCLUSION: Postprocedural enhanced sonography has the potential to guide
      completion of radiofrequency ablation at the time of initial therapy when
      residual disease is detected. The procedure is less accurate in detection of
      residual disease than is either delayed enhanced sonography or CT or MRI.

PMID- 16632691
TI  - Percutaneous radiofrequency ablation for hepatocellular carcinoma before liver
      transplantation: a prospective study with histopathologic comparison.
AB  - OBJECTIVE: The aims of this study were to determine the feasibility and efficacy
      of percutaneous radiofrequency ablation in patients with hepatocellular carcinoma
      waiting for liver transplantation and to compare the radiologic and pathologic
      findings. SUBJECTS AND METHODS: Twenty-six patients with 35 hepatocellular
      carcinomas were addressed for transplantation. Complications of the procedures
      were recorded. Primary and secondary technique effectiveness and causes of
      exclusion from the waiting list were assessed. After transplantation, tumor
      recurrence was evaluated for at least 1 year in all patients. Radiologic
      pathologic comparison of the explant was performed. RESULTS: Percutaneous
      radiofrequency ablation was performed in 21 (81%) patients for 28 tumors. Both
      minor and major complications occurred in three patients (10% each per session).
      The rates of primary technique effectiveness, secondary technique effectiveness
      for percutaneous radiofrequency ablation alone (seven tumors), and combined
      percutaneous radiofrequency ablation and transcatheter arterial chemoembolization
      (three tumors) were 56%, 76%, and 86%, respectively. After a mean follow-up of
      11.9 months, 16 patients (76%) received transplants, whereas five patients were
      excluded from the waiting list because of distant tumor progression (n =3, 14%)
      or other causes (n = 2, 10%). After transplantation, tumor recurred in one (6%)
      of 16 patients. Histopathologic examinations were performed for 13 (81%) of 16
      patients and showed complete necrosis and satellite nodules in, respectively, 12
      (75%) and seven (44%) of 16 tumors. CONCLUSION: Percutaneous radiofrequency
      ablation can be performed on hepatocellular carcinoma patients waiting for
      transplantation, allows most patients to undergo transplantation, and does not
      impair posttransplantation outcomes. The procedure produces complete necrosis of
      the treated tumor in most cases but is associated with a high rate of satellite
      nodules.

PMID- 16632692
TI  - Radiofrequency ablation of peripheral liver tumors: intraperitoneal 5% dextrose
      in water decreases postprocedural pain.
AB  - OBJECTIVE: Our objective was to evaluate the clinical efficacy of the
      intraperitoneal instillation of 5% dextrose in water (D5W) during radiofrequency
      ablation of peripheral liver tumors for decreasing postradiofrequency pain and
      narcotic use. MATERIALS AND METHODS: This case-control study compared the
      hospital course of the last 20 patients to undergo radiofrequency ablation of
      peripheral liver tumors at our institution. Ten consecutive subjects in the D5W
      group (seven women and three men; age range, 37-78 years; mean, 58 years) were
      pretreated with intraperitoneal D5W (average, 963 +/- 436 [SD] mL) before the
      ablation. This group was compared with a control group of 10 patients (five men
      and five women; age range, 36-73 years; mean, 54 years) who did not receive
      intraperitoneal D5W. The size of the ablation zone, degree of liver capsule
      involvement, number of burns, patient-reported pain, patient-controlled analgesia
      use, and length of hospital stay were recorded and compared between the groups.
      RESULTS: The patients in the D5W group reported significantly less pain in the
      first 24 hr after the procedure than did the controls (2.3 vs 6.3, p = 0.003)
      despite a significant decrease in patient-controlled analgesia use (17.3 vs 125.1
      mg of morphine, p = 0.003). The differences in pain and patient-controlled
      analgesia use were greatest in the first 16 hr and decreased over time in both
      groups. The total volume of ablation (61.9 vs 45.2 cm(3), p = 0.44), liver
      surface involvement (6.2 vs 6.0 cm, p = 0.73), and number of burns (1.8 vs 1.1, p
      = 0.14) were slightly higher in the D5W group than in the control group, but this
      difference was not statistically significant. CONCLUSION: Pretreatment with
      intraperitoneal D5W before radiofrequency ablation of peripheral liver tumors
      decreased pain, narcotic use, and length of hospital stay. The effect of
      pretreatment with D5W is greatest in the first 16 hr after the procedure.

PMID- 16632693
TI  - Efficacy of transhepatic radiofrequency ablation of renal cell carcinoma.
AB  - OBJECTIVE: The purpose of this report is to describe an alternative, using a
      transhepatic route, to CT guidance of radiofrequency ablation of renal masses.
      CONCLUSION: In four supine patients, radiofrequency ablation of a right renal
      mass was performed under sonographic guidance. The radiofrequency ablation needle
      was placed transhepatically into the mass. Color sonography was useful in guiding
      needle placement and avoiding intervening vessels in the liver and kidney. This
      technique may be used in selected patients as an alternative to CT guidance of
      radiofrequency ablation.

PMID- 16632694
TI  - Radiofrequency ablation of hepatocellular carcinoma: long-term experience with
      expandable needle electrodes.
AB  - OBJECTIVE: Our objective was to determine the efficacy of radiofrequency
      ablation, using expandable electrodes, in the treatment of patients with
      hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: In a 5-year period (1998
      2003), 68 HCCs in 59 patients (age range, 47-88 years) were treated
      percutaneously with radiofrequency ablation using expandable needle electrodes.
      The mean lesion diameter was 3.1 cm (range, 1-12 cm). Fifty-one of 59 patients
      were in Child-Pugh class A, and eight were in class B. Follow-up was performed by
      helical CT at 1, 4, and 6 months and every 6 months after that. The mean follow
      up was 24.1 months (range, 6-60 months). Survival and disease-free survival rates
      were evaluated separately by statistical analysis. Any complications were
      reported during follow-up. RESULTS: Cumulative survival rates were 94.4%, 65%,
      and 43.1% at 1, 3, and 5 years, respectively. Median survival time was 23.6
      months (range, 4-62 months). Maximum tumor diameter was associated with the
      probability of survival: 73% among patients with lesion diameters of 3 cm or
      less, 76.5% among patients with lesion diameters of 3-5 cm, and only 40% among
      patients with lesion diameters of more than 5 cm (p = 0.05, log-rank test; p =
      0.07, Tarone-Ware test). In 34 (57.6%) of 59 patients during follow-up, new
      nodules noncontiguous with the treated nodule developed in the liver (tumor
      recurrences). Median disease-free survival rates were 32.1%, 28.1%, and 17.5% at
      1, 2, and 3 years, respectively. One major complication occurred (hemoperitoneum
      that required transfusion). CONCLUSION: Radiofrequency ablation with expandable
      electrodes is safe and effective in the treatment of HCC.

PMID- 16632695
TI  - Saline-infused bipolar radiofrequency ablation of high-risk spinal and paraspinal
      neoplasms.
AB  - OBJECTIVE: We present three cases of symptomatic high-risk metastases involving
      the vertebral body treated using infused bipolar radiofrequency ablation either
      alone or in combination with vertebroplasty. CONCLUSION: In our experience, the
      bipolar technique can reduce the risk of spinal cord damage in radiofrequency
      ablation of lesions within 1 cm of neural structures and involving paravertebral
      soft tissue.

PMID- 16632696
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma: effect of
      histologic grade on therapeutic results.
AB  - OBJECTIVE: The purpose of our study was to assess the therapeutic results of
      radiofrequency ablation of hepatocellular carcinoma (HCC) based on the histologic
      grades of the tumors. SUBJECTS AND METHODS: Between April 1999 and December 2003,
      95 patients with nodular HCC were treated with percutaneous radiofrequency
      ablation. All tumors were histologically proven by sonography-guided percutaneous
      biopsy and were classified as Edmondson-Steiner grade I HCC (n = 38) (mean, 2.3
      cm) (group 1), grade II HCC (n = 50) (mean, 2.4 cm) (group 2), or grade III HCC
      (n = 7) (mean, 2.8 cm) (group 3). All patients underwent contrast-enhanced three
      phase helical CT examination before and after radiofrequency ablation. After
      retrospective review of the medical records and follow-up CT examinations, the
      rates of technique effectiveness, local tumor progression, cumulative survival,
      and cancer-free survival using a Kaplan-Meier method were calculated and compared
      among the groups. RESULTS: Technique effectiveness rates in groups 1, 2, and 3
      were 87% (27/31), 71% (30/42), and 43% (3/7), respectively, with statistical
      significance (p = 0.032). Local tumor progression rates in groups 1, 2, and 3
      were 16% (5/31), 36% (15/42), and 71% (5/7), respectively, with statistical
      significance (p = 0.013). Five-year cumulative survival rates in groups 1, 2, and
      3 were 71%, 44%, and 43%, respectively, with no statistical significance (p >
      0.05). Four-year cancer-free survival rates in groups 1, 2, and 3 were 39%, 10%,
      and 0%, respectively (p < 0.05 for groups 1 vs 2; p > 0.05 for groups 1 vs 3 and
      groups 2 vs 3). CONCLUSION: The histologic grade of HCC is an important factor
      influencing therapeutic results with survival after radiofrequency ablation.

PMID- 16632698
TI  - Medical terminology.

PMID- 16632699
TI  - BRCA1-associated breast carcinomas frequently present with benign sonographic
      features.

PMID- 16632703
TI  - Evaluation of the radial artery.

PMID- 16632705
TI  - On measuring costs and profit.

PMID- 16632707
TI  - Inadvertent injection of inappropriate contrast material.

PMID- 16632708
TI  - "Computed tomography of the liver"--a commentary.

PMID- 16632709
TI  - MRI features after radiofrequency ablation of osteoid osteoma with cooled probes
      and impedance-control energy delivery.
AB  - OBJECTIVE: The purposes of our study were to determine the temporal changes in MR
      signal in bone after radiofrequency ablation of osteoid osteoma and the size of
      the zone of marrow signal change produced by the radiofrequency technique and to
      compare the size of the zone with published data for radiofrequency ablation with
      manual-control protocols. MATERIALS AND METHODS: Radiofrequency ablation was
      performed in 10 patients with a clinical and radiologic diagnosis of osteoid
      osteoma. A cooled radiofrequency probe was inserted in the nidus. Twelve minutes
      of radiofrequency energy was applied from a 200-W radiofrequency generator in an
      impedance-control setting. MRI with multiplanar turbo spin-echo T1-weighted and
      STIR sequences was performed at 1, 7, and 28 days after the procedure in seven
      patients. The three remaining patients had follow-up imaging at 28 days only. The
      images were reviewed by two radiologists who categorized the imaging features and
      measured the marrow zone of signal alteration when visible. The size of the zone
      of marrow signal change produced by the radiofrequency technique was compared
      with published data for radiofrequency ablation with manual-control protocols.
      RESULTS: A 1-mm band of homogeneous altered marrow signal distributed
      symmetrically parallel to the entire probe tract was seen earliest, at 1 day, in
      the femoral neck lesion treated with the 2-cm probe. The band was low signal on
      the T1 sequence and high signal on the STIR sequence, and the diameter of the
      zone was 27 mm. By 7 days, five of the seven treated bones showed a band of
      marrow signal alteration. By 28 days, all 10 treated bones had a band of marrow
      signal alteration. The interband distance at 90 degrees to the probe measured on
      STIR images at 28 days was a mean of 20.9 mm (confidence interval, 16.1-25.7 mm
      [p < 0.05]; range +/- measurement error, 10.5-35 +/- 1.64 mm) with a 1-cm probe
      and 30.5 mm (measurement error, +/- 0.78 mm) on T1 images without contrast
      material when a 2-cm exposed-tip probe was used. Higher-output generators with
      impedance-control software and internally cooled radiofrequency probes with
      longer exposed tips produce larger zones of marrow signal change than expected
      with manual-control protocols. CONCLUSION: MRI allows detection of temporal
      marrow signal change after radiofrequency ablation. The marrow signal change with
      a high-energy delivery protocol is larger than manual-control protocols.

PMID- 16632710
TI  - Therapeutic efficacy of facet joint blocks.
AB  - OBJECTIVE: The objective of our study was to investigate outcome predictors of
      short- and medium-term therapeutic efficacy of facet joint blocks. MATERIALS AND
      METHODS: Forty-two patients with chronic lower back pain who were undergoing
      facet joint blocks at one (n = 29) or two (n = 13) levels were analyzed. All
      patients underwent MRI or CT of the lumbar spine within 5 months before the facet
      joint blocks. The facet joint blocks were performed under fluoroscopic guidance.
      A small amount (< 0.3 mL) of iodinated contrast agent, 0.5 mL of local
      anesthetics and 0.5 mL of steroids, were injected. The initial pain response was
      prospectively assessed using a visual analogue scale. Additional data, including
      short-term effect (> 1 week) and medium-term effect (> 3 months), were collected
      by a structured telephone interview. CT and MRI were reviewed with regard to the
      extent of facet joint abnormalities. Multiple logistic regression analyses were
      conducted to identify outcome predictor for efficacy of facet joint blocks.
      RESULTS: A positive immediate effect was seen in 31 patients (74%). A positive
      medium-term effect was found in 14 patients (33%). Pain alleviated by motion (p =
      0.035) and the absence of joint-blocking sensation (p = 0.042) predicted pain
      relief. However, the extent of facet joint osteoarthritis on MRI and CT was not a
      significant predictor for outcome (p = 0.57-0.95). CONCLUSION: Facet joint blocks
      appear to have a beneficial medium-term effect in one third of patients with
      chronic lower back pain and may therefore be a reasonable adjunct to nonoperative
      treatment. However, outcome appears to depend on clinical, not on morphologic,
      imaging findings.

PMID- 16632711
TI  - Shoulder pain and disability: comparison with MR findings.
AB  - OBJECTIVE: The objective of our study was to compare the level of disability
      induced by shoulder pain as reported by patients on the L'Insalata Self
      Administered Questionnaire (SAQ) with shoulder MRI results. MATERIALS AND
      METHODS: One thousand seventy-nine consecutive patients referred for shoulder MRI
      were asked to complete the L'Insalata SAQ. Results from the L'Insalata SAQ and
      MRI were cross-tabulated and analyzed with multivariable linear regression.
      RESULTS: No statistical relationship could be found between the level of pain,
      impairment, and disability as reported on the L'Insalata SAQ and the location and
      size of full-thickness tears of the rotator cuff as observed on MRI. Pain and
      disability are significantly linked to the presence of supraspinatus tendon
      lesions and the presence of bursitis, but these factors contribute little to the
      symptoms. Patients with biceps tendinopathy did not experience increased pain
      when compared with patients without biceps tendinopathy or with biceps tendon
      rupture. CONCLUSION: No statistical relationship was found between the level of
      pain and disability and the size and location of full-thickness tears of the
      rotator cuff.

PMID- 16632712
TI  - Predictors of carpal tunnel syndrome: accuracy of gray-scale and color Doppler
      sonography.
AB  - OBJECTIVE: The purpose of this study was to retrospectively assess the accuracy
      of gray-scale and color Doppler sonography in the diagnosis of carpal tunnel
      syndrome. MATERIALS AND METHODS: A total of 206 wrists in 151 patients with a
      clinical suspicion of carpal tunnel syndrome were examined with high-resolution
      sonography using a 7-15-MHz linear array transducer. The presence of median nerve
      swelling, edema, and flattening and increased bowing of the flexor retinaculum
      was evaluated with gray-scale sonography, and the presence of nerve
      hypervascularization was evaluated with color Doppler sonography. Sensitivity and
      specificity were calculated for each sonographic feature in comparison with nerve
      conduction studies as the standard of reference. Multivariate logistic regression
      analysis was used to determine variables predictive of carpal tunnel syndrome.
      RESULTS: Carpal tunnel syndrome was confirmed in 172 wrists at nerve conduction
      studies. A median nerve cross-sectional area of at least 0.11 cm2 was calculated
      as a definition of median nerve swelling. In comparison with nerve conduction
      studies, nerve swelling showed the highest accuracy (91%) among gray-scale
      sonography criteria, and the presence of intraneural hypervascularization showed
      the highest accuracy (95%) among all sonography criteria. Logistic regression
      analysis showed that nerve hypervascularization was the only variable that
      independently predicted median nerve entrapment (odds ratio, 16.4; 95% confidence
      interval, 8.7-31.1; p <0.001). CONCLUSION: Color Doppler sonography is more
      accurate than gray-scale sonography for characterizing median nerve involvement
      in patients with suspected carpal tunnel syndrome.

PMID- 16632713
TI  - Alterations of the thoracic spine in Marfan's syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine if the thoracic vertebral
      elements are altered in patients with Marfan's syndrome. MATERIALS AND METHODS:
      Thirty patients underwent helical CT of the thorax because of suspected thoracic
      aortic dilatation and acute dissection. Thirteen had Marfan's syndrome and 17 did
      not. Two reviewers, unaware of the final diagnosis, evaluated the images by
      consensus for laminar thickness, foraminal width, dural sac ratios, and vertebral
      scalloping for T2-T12. RESULTS: At T9-T12, dural sac ratios at the midcorpus
      level (p = 0.031) and foraminal width (p = 0.0124) were significantly greater in
      the patients with Marfan's syndrome than in the patients without. Dural sac
      ratios at lower endplate levels (p = 0.0685), laminar thickness (p = 0.951), and
      vertebral scalloping (p = 0.24) were not significantly greater in the patients
      with Marfan's syndrome than in the patients without. CONCLUSION: Because the
      phenotypic expression of Marfan's syndrome is variable, information on the spine
      from thoracic studies in combination with major criteria may be helpful
      clinically.

PMID- 16632714
TI  - Percutaneous sacroplasty: long-axis injection technique.
AB  - OBJECTIVE: Sacroplasty, or the injection of percutaneous polymethyl methacrylate
      into a sacral insufficiency fracture, has been previously described using needle
      placement in the short axis of the sacrum. We describe a new technique of needle
      placement along the long axis of the sacrum. CONCLUSION: This approach is easier
      to perform and results in improved cement distribution along the length of the
      sacral ala.

PMID- 16632715
TI  - Multiple posterior vertebral fusion abnormalities: a case report and review of
      the literature.

PMID- 16632716
TI  - Physeal widening in the knee due to stress injury in child athletes.
AB  - OBJECTIVE: The objective of our study was to describe the MRI appearance of and
      possible mechanism responsible for physeal widening in the knees of high-level
      child athletes. CONCLUSION: Widened physes in the knees of skeletally immature
      child athletes have MR signal characteristics similar to the normal physis but
      likely are a sign of stress injury. These children should cease the offending
      sport and rest the knee to allow rapid healing.

PMID- 16632717
TI  - Acute pulmonary embolism on MDCT of the chest: prediction of cor pulmonale and
      short-term patient survival from morphologic embolus burden.
AB  - OBJECTIVE: To predict cor pulmonale and short-term outcome in patients with
      pulmonary embolism (PE), we retrospectively investigated three morphology-based
      MDCT systems for scoring pulmonary artery obstruction. MATERIALS AND METHODS:
      Eighty-nine consecutive patients (51 men and 38 women; age range, 23-83 years;
      median, 63.3 years) with an MDCT diagnosis of acute PE were included in the
      study. Sixty-four patients had a coexisting malignancy. PE severity was assessed
      by two masked observers using three percentage arterial obstruction indexes: two
      severity scores adapted from conventional angiography (excluding and including
      arterial branch obstruction grading: scores A and B, respectively) and a CT
      derived severity score (index C). Echocardiographic reports were reviewed for
      elevation of right ventricular pressure. Obstruction index results were analyzed
      for correlation with pulmonary artery pressures and for prediction of cor
      pulmonale and 30-day survival. Statistical analysis included kappa, analysis of
      variance, linear correlation, chi-square, and logistic regression tests. RESULTS:
      Kappa values of 0.89, 0.82, and 0.78 were obtained for interobserver agreement on
      PE severity for indexes A, B, and C, respectively. PE severity was moderate but
      varied significantly between the scores (for index A: median, 25.0%; range, 6.3
      100; for index B: median, 12.5%; range, 3.1-65.6; for index C: median, 7.1%;
      range, 0.65-65.8; p < 0.0001 [analysis of variance]). Index C correlated best
      with pulmonary artery pressures (r = 0.69; p < 0.0016) and the presence of cor
      pulmonale (p = 0.0051; odds ratio [OR], 1.20/percentage increase [95% confidence
      interval, 1.05-1.35]; for an index C cutoff of 21.3%: p = 0.0001; positive
      predictive value, 1; negative predictive value, 0.87). Eight patients died within
      30 days after CT. The PE severity of indexes A and B was not associated with
      patient outcome (p > 0.05). With score C, PE severity was a significant predictor
      of early death (p = 0.018; OR, 1.03/percentage increase [95% confidence interval,
      1.00-1.06]; for an index C cutoff of 21.3%: p = 0.018; overall OR, 6.77; positive
      predictive value, 0.24; negative predictive value, 0.96). CONCLUSION: Mastora
      score was a significant predictor of cor pulmonale and short-term outcome and may
      therefore allow therapy and risk stratification in patients with acute PE.

PMID- 16632718
TI  - Quantification of thin-section CT lung attenuation in acute pulmonary embolism:
      correlations with arterial blood gas levels and CT angiography.
AB  - OBJECTIVE: The purposes of this study were to investigate the frequency histogram
      of lung attenuation on CT angiography (CTA) in patients with and without acute
      pulmonary embolism (PE) and to evaluate the relation of the frequency histogram
      of lung attenuation and hypoxemia. MATERIALS AND METHODS: Twenty-six patients
      with PE and 11 patients without PE who underwent CTA were evaluated with
      frequency histograms. We obtained quantitative parameters such as mean lung
      attenuation, median lung attenuation, SD, skewness, kurtosis, and the proportion
      of lung attenuation except for the median +/- 50 H (P +/- 50 H). Lung attenuation
      was also assessed visually and scored. The relationship between those histogram
      parameters, or visual score, and Pa(O2) was evaluated. CTA scores for evaluation
      of the degree of pulmonary artery obstruction were obtained, and the relation
      with Pa(O2) was assessed. RESULTS: No significant differences were found in mean
      lung attenuation and median lung attenuation between patients with and without
      PE. Meanwhile, SD, skewness, kurtosis, and P +/- 50 H were significantly
      different between patients with and without PE (p = 0.0003, 0.0071, 0.0047, and
      0.0028, respectively) and significantly correlated with Pa(O2) (r = -0.770,
      0.797, 0.786, -0.871, respectively). Significant differences were found in visual
      scores between patients with and without PE (p < 0.0001). There were significant
      but relatively low correlations between CTA score and arterial blood gas levels
      (r = -0.442, p = 0.03). CONCLUSION: In patients with acute PE, heterogeneity in
      lung attenuation is more prominent than in patients without PE.

PMID- 16632719
TI  - Computer-aided detection in screening CT for pulmonary nodules.
AB  - OBJECTIVE: Our objective was to evaluate the performance of a computer-aided
      detection (CAD) system for pulmonary nodule detection using low-dose screening CT
      images. MATERIALS AND METHODS: One hundred fifty consecutive low-dose screening
      CT examinations were independently evaluated by a radiologist and a CAD pulmonary
      nodule detection system (R2 Technology) designed to identify nodules larger than
      4 mm in maximum long-axis diameter. All discrepancies between the two techniques
      were reviewed by one of another two radiologists working in consensus with the
      initial interpreting radiologist, and a "true" nodule count was determined.
      Detected nodules were classified by size, density, and location. The performance
      of the initial radiologist and the CAD system were compared. RESULTS: The
      radiologist detected 518 nodules and the CAD system, 934 nodules. Of the 1,106
      separate nodules detected using the two techniques, 628 were classified as true
      nodules on consensus review. Of the true nodules present, the radiologist
      detected 518 (82%) of 628 nodules and the CAD, 456 (73%) of 628 nodules. All 518
      radiologist-detected nodules were true nodules, and 456 (49%) of 934 of CAD
      detected nodules were true nodules. The radiologist missed 110 true nodules that
      were only detected by CAD. In six patients, these were the only nodules detected
      in the examination, changing the imaging follow-up protocol. CAD identified 478
      lesions that on consensus review were false-positive nodules, a rate of 3.19
      (478/150) per patient. CONCLUSION: CAD detected 72.6% of true nodules and
      detected nodules in six (4%) patients not identified by radiologists, changing
      the imaging follow-up protocol of these subjects. In this study, the combined
      review of low-dose CT scans by both the radiologist and CAD was necessary to
      identify all nodules.

PMID- 16632720
TI  - Adenovirus pneumonia in adults: radiographic and high-resolution CT findings in
      five patients.
AB  - OBJECTIVE: The purpose of this study was to describe the radiographic and high
      resolution CT (HRCT) findings of adenovirus pneumonia in five patients.
      CONCLUSION: Adenovirus pneumonia in adults appears as bilateral patchy
      parenchymal opacities on chest radiographs and as bilateral ground-glass
      opacities with a random distribution with or without consolidation on HRCT
      images. These findings, however, are not specific for adenovirus pneumonia.

PMID- 16632721
TI  - Lymphoepithelioma-like carcinoma of the lung: radiologic features of an uncommon
      primary pulmonary neoplasm.
AB  - OBJECTIVE: The purpose of this study was to review the chest radiographic, CT,
      and MRI appearances of primary pulmonary lymphoepithelioma-like carcinoma (LELC).
      CONCLUSION: Primary pulmonary LELC is histopathologically identical to
      nasopharyngeal carcinoma. The radiographic, CT, and MRI features of primary
      pulmonary LELC are nonspecific, often resembling those of bronchogenic carcinoma.
      Primary pulmonary LELC usually presents as a poorly circumscribed, enhancing,
      peripheral solitary pulmonary nodule on CT; necrosis may be present and is
      considered a poor prognostic sign. MRI shows isointense to low-intensity signal
      on T1-weighted images and mildly increased signal on T2-weighted images;
      enhancement of abnormal tissue is typical. Most patients present with early-stage
      disease. Primary pulmonary LELC should be suspected in selected patients and
      requires differentiation from bronchogenic carcinoma and metastatic
      nasopharyngeal carcinoma.

PMID- 16632722
TI  - Acute schistosomiasis in nonimmune travelers: chest CT findings in 10 patients.
AB  - OBJECTIVE: We describe the findings of unenhanced chest CT in 10 patients with
      acute schistosomiasis. CONCLUSION: Despite the absence of pulmonary symptoms in
      four individuals, all patients had parenchymal abnormalities. Small pulmonary
      nodules were the most common finding, identified in nine patients. These nodules
      ranged in size from 2 to 5 mm in five patients, with larger nodules ranging up to
      15 mm seen in four patients. In one patient, the only parenchymal abnormality was
      a single 5-mm focus of ground-glass attenuation. No relationship was seen between
      either the presence of pulmonary symptoms or the presence of peripheral
      eosinophilia and the severity of parenchymal disease. No additional significant
      findings were identified.

PMID- 16632723
TI  - Benign tumors of the tracheobronchial tree: CT-pathologic correlation.
AB  - OBJECTIVE: The purpose of this essay is to illustrate the CT findings of variable
      benign tumors of the tracheobronchial tree and to correlate the CT and pathologic
      findings in 17 patients. CONCLUSION: The tracheal tumors were eccentric, well
      defined, polypoid masses in all cases. The endobronchial tumors were masses
      confined within the bronchus in all cases, and atelectasis or pneumonia of the
      distal parenchyma was frequently associated. Of the six hamartomas, one was a
      fatty mass, and two were nodules with calcification. The others were soft-tissue
      density nodules. The lipomas manifested as fat density on CT scans in both cases.
      The other benign tumors were low-attenuating, soft-tissue-density masses without
      characteristic findings on CT scans.

PMID- 16632724
TI  - Extraforaminal meningioma with extrapleural space extension.

PMID- 16632725
TI  - Left atrial wall hematoma after radiofrequency ablation for atrial fibrillation.

PMID- 16632726
TI  - Role of radiologic features in the management of papillary lesions of the breast.
AB  - OBJECTIVE: The purpose of our study was to assess the role of imaging and core
      biopsy in the management of patients with papillary lesions of the breast.
      MATERIALS AND METHODS: Clinical records and mammographic and sonographic findings
      of 40 women with papillary lesions in the breast were retrieved. The imaging
      features and cytologic findings were correlated with histologic findings.
      RESULTS: Fifty-six papillary lesions in 40 patients underwent either mastectomy,
      segmental duct resection, or excision biopsy. There were three papillary
      carcinomas, 13 papillaryal lesions with carcinoma in situ, one atypical
      papilloma, four sclerosed papillomata, and 35 papillomata. Of these lesions,
      37.5% (21/56) and 82.1% (46/56) could be detected on mammography and sonography,
      respectively. Galactography and dilated ducts helped to suggest the papillary
      nature of the lesions. However, mammography and sonography were not able to
      predict malignancy (sensitivity, 69% and 56%, respectively; specificity, 25% and
      90%; positive predictive value [PPV], 60% and 75%; and negative predictive value
      [NPV], 33% and 90%). Combined interpretation of mammography and sonography gave a
      sensitivity of 61%, specificity of 33%, PPV of 85%, and NPV of 13%. Fine-needle
      aspiration gave a sensitivity of 44%, specificity of 68%, PPV of 31%, and NPV of
      79%, whereas core biopsy gave a sensitivity of 82%, specificity of 100%, PPV of
      100%, and NPV of 83% in the diagnosis of malignancy. CONCLUSION: Radiologic
      features are not sufficiently sensitive or specific to differentiate benign from
      malignant papillary lesions. Fine-needle aspiration and core biopsy have
      pitfalls, and the need for surgical excision of all papillary lesions should be
      revisited.

PMID- 16632727
TI  - Is surgical excision warranted after benign, concordant diagnosis of papilloma at
      percutaneous breast biopsy?
AB  - OBJECTIVE: The study objective was to determine the cancer frequency in lesions
      yielding a benign, concordant diagnosis of papilloma at percutaneous breast
      biopsy. MATERIALS AND METHODS: Retrospective review was performed of 3,864
      lesions that had percutaneous imaging-guided biopsy. In 50 lesions (1.3%),
      percutaneous biopsy yielded a benign, concordant diagnosis of papilloma. Surgical
      pathology (n = 25) or minimum 2 years' mammographic follow-up (n = 10) was
      available for 35 lesions that had biopsy with 11-gauge vacuum-assisted (n = 20)
      or 14-gauge automated (n = 15) needles. Medical records, imaging studies, and
      histologic results were reviewed. RESULTS: Cancer was found in five (14%) of the
      35 lesions yielding a benign, concordant diagnosis of papilloma at percutaneous
      biopsy. Cancer histology was ductal carcinoma in situ in four (80%) and node
      negative invasive cancer in one. Four (80%) of five cancers were identified due
      to interval change at follow-up (median, 22 months; range, 7-25 months). In six
      (17%) of 35 lesions, surgery revealed high-risk lesions including atypical ductal
      hyperplasia (n = 3), radial scar (n = 2), and lobular carcinoma in situ (n = 1).
      There was a significantly (p = 0.02) higher frequency of cancer or high-risk
      lesion in women with multiple versus solitary papillomas and a trend (p = 0.09)
      toward a higher cancer rate in women with versus without a family history of
      breast cancer. Breast cancer history, menopausal status, mammographic pattern,
      biopsy method, and removal of imaging target had no significant impact on cancer
      rate. CONCLUSION: In our study of percutaneously diagnosed papillomas, surgery
      revealed cancer in 14% and high-risk lesions in 17%. Lesions yielding a benign,
      concordant diagnosis of papilloma at percutaneous biopsy may warrant surgical
      excision.

PMID- 16632728
TI  - Streaming detection for evaluation of indeterminate sonographic breast masses: a
      pilot study.
AB  - OBJECTIVE: Streaming detection is a novel sonography technique that uses
      ultrasonic energy to induce movement in cyst fluid that is detected on Doppler
      sonography. This pilot study evaluates the utility of streaming detection for
      differentiating cysts from solid masses in breast lesions that are indeterminate
      on sonography. SUBJECTS AND METHODS: Thirty-nine lesions-11 simple cysts and
      seven solid masses (control group) and 21 masses with indeterminate findings for
      the diagnosis of a cyst versus a solid lesion (study group)-in 34 patients were
      evaluated using streaming detection. All lesions underwent cyst aspiration or
      biopsy (n = 35) or were diagnosed simple cysts (n = 4) on sonography. Lesion size
      and depth were recorded. Streaming detection software was placed on conventional
      sonography units. Acoustic pulses were focused on the lesion, and if fluid
      movement was generated, it was seen on the spectral Doppler display as velocity
      away from the transducer. Lesions were then aspirated or underwent biopsy, and
      the viscosity of the aspirated fluid was recorded. The sensitivity and
      specificity of the technique and the effect of cyst size, cyst depth, and fluid
      viscosity in diagnosing fluid-filled cysts were assessed. RESULTS: Overall, 31
      cysts and eight solid masses (seven benign, one carcinoma) were diagnosed in the
      study and control groups. Aspiration of indeterminate lesions resulted in 20
      cysts and one solid mass. Lesions ranged in size from 4 to 47 mm and in depth
      from 4 to 29 mm. In the control group, streaming detection correctly showed nine
      of the 11 simple cysts (sensitivity, 82%; positive predictive value, 100%), and
      acoustic streaming was absent in all seven solid masses (specificity, 100%;
      negative predictive value, 78%). Of the indeterminate lesions, streaming
      detection allowed correct identification of 10 of 20 cysts (sensitivity, 50%;
      positive predictive value, 100%). Acoustic streaming was not detected in the one
      solid study group lesion. Neither cyst size or depth nor fluid viscosity had a
      significant effect on the ability to detect fluid. CONCLUSION: The streaming
      detection technique improved differentiation of cysts from solid masses in
      indeterminate lesions and has potential for reducing the number of recommended
      cyst aspirations for the diagnosis of indeterminate breast masses.

PMID- 16632729
TI  - Role of sonography in the diagnosis of axillary lymph node metastases in breast
      cancer: a systematic review.
AB  - OBJECTIVE: The purpose of our study was to evaluate the accuracy of sonography
      and sonographically guided biopsy in the preoperative diagnosis of metastatic
      invasion of the axilla in patients with breast carcinoma. MATERIALS AND METHODS:
      We performed a MEDLINE search (keywords, "sonography" OR "ultrasound" AND
      "axillary") and a manual search of the references of relevant studies and reviews
      of preoperative diagnosis on sonography of possible axillary metastases. The gold
      standard required was axillary lymph node dissection; we accepted sentinel node
      biopsy as an alternative gold standard. Considering the sonographic findings and
      the results of the sonographically guided biopsy, the sensitivity and specificity
      were calculated using metaanalysis. We also checked the existence of
      heterogeneity of the summary results. RESULTS: Sixteen articles were selected. In
      sonography of axillae without palpable nodes, and using lymph node size as the
      criterion for positivity, sensitivity varied between 48.8% (95% confidence
      interval, 39.6-58%) and 87.1% (76.1-94.3%) and specificity, between 55.6% (44.7
      66.3%) and 97.3% (86.1-99.9%). When lymph node morphology was used as the
      criterion for positivity, sensitivity ranged from 26.4% (15.3-40.3%) to 75.9%
      (56.4-89.7%) and specificity, from 88.4% (82.1-93.1%) to 98.1% (90.1-99.9%). The
      results are different if axillae with palpable nodes are included. The
      sonographically guided biopsy shows a sensitivity that varies between 30.6% (22.5
      39.6%) and 62.9% (49.7-74.8%) and a specificity of 100% (94.8-100%). Many of the
      summary results obtained after meta-analysis show a heterogeneity that
      disappears, on occasion, on excluding the studies that use a double gold
      standard. CONCLUSION: Axillary sonography is moderately sensitive and fairly
      specific in the diagnosis of axillary metastatic involvement. Sonographically
      guided biopsy of the sonographically suspicious nodes somewhat increases the
      specificity, which reaches 100%. Negative sonographic results do not exclude
      axillary lymph node metastases.

PMID- 16632730
TI  - Imaging of lymphatic vessels in breast cancer-related lymphedema: intradermal
      versus subcutaneous injection of 99mTc-immunoglobulin.
AB  - OBJECTIVE: The disordered physiology that results from axillary lymph node
      clearance surgery for breast cancer and that leads to breast cancer-related
      lymphedema is poorly understood. Rerouting of lymph around the axilla or through
      new pathways in the axilla may protect women from breast cancer-related
      lymphedema. The aim of the study was to compare intradermal with subcutaneous
      injection of technetium-99m ((99m)Tc)-labeled human polyclonal IgG (HIG) with
      respect to lymphatic vessel imaging. MATERIALS AND METHODS: Six women with breast
      cancer-related lymphedema underwent unilateral upper limb lymphoscintigraphy,
      using a web space injection of (99m)Tc-labeled HIG, after intradermal and
      subcutaneous injections on separate occasions. Multiple sequential images were
      obtained of the affected upper limb and torso over 3 hr on each occasion.
      Accumulation of activity in blood was quantified from venous blood samples taken
      from the opposite arm. RESULTS: Imaging after intradermal injection clearly
      showed discrete lymphatic vessels in five of six patients, in contrast to imaging
      after subcutaneous injection, which did not show any discrete vessels in any
      patient. Intradermal injection resulted in more rapid visualization of cutaneous
      lymph rerouting than subcutaneous injection in six of six patients. Recovery of
      injected (99m)Tc-labeled HIG in venous blood was greater after intradermal
      injection in six of six patients. CONCLUSION: In patients with breast cancer
      related lymphedema, lymphatic vessels are more clearly depicted after intradermal
      than subcutaneous injection as a result of direct access of radiotracer to dermal
      lymphatics. This finding has implications for imaging lymphatic vessel
      regeneration and lymph rerouting.

PMID- 16632731
TI  - Mucocelelike lesions of the breast: mammographic findings with pathologic
      correlation.
AB  - OBJECTIVE: The purpose of this study was to review the imaging features of
      mucocelelike breast lesions, correlate the mammographic and pathologic findings,
      and determine recommendations for management. CONCLUSION: Mucocelelike lesions
      are more common than previously reported and are likely to exhibit indeterminate
      calcifications on mammography. Diagnosis is most often made with Mammotome
      biopsy. A large number of patients have associated atypia or carcinoma. For
      patients with purely benign histologic findings at Mammotome biopsy, optimal
      management should be excisional biopsy to exclude associated malignancy.

PMID- 16632732
TI  - Blunt abdominal trauma: emergency contrast-enhanced sonography for detection of
      solid organ injuries.
AB  - OBJECTIVE: The objective of our study was to prospectively compare the diagnostic
      value of sonography and contrast-enhanced sonography with CT for the detection of
      solid organ injuries in blunt abdominal trauma patients. SUBJECTS AND METHODS:
      Sonography, contrast-enhanced sonography, and CT were performed to assess
      possible abdominal organ injuries in 69 nonconsecutive hemodynamically stable
      patients with blunt abdominal trauma and a strong clinical suspicion of abdominal
      lesions. Sonography and contrast-enhanced sonography findings were compared with
      CT findings, the reference standard technique. RESULTS: Thirty-two patients had
      35 abdominal injuries on CT (10 kidney or adrenal lesions, seven liver lesions,
      17 spleen lesions, and one retroperitoneal hematoma). Sixteen lesions were
      detected on sonography, and 32 were seen on contrast-enhanced sonography. The
      sensitivity and specificity of sonography were 45.7% and 91.8%, respectively, and
      the positive and negative predictive values were 84.2% and 64.1%, respectively.
      Contrast-enhanced sonography had a sensitivity of 91.4%, a specificity of 100%,
      and positive and negative predictive values of 100% and 92.5%, respectively.
      CONCLUSION: Contrast-enhanced sonography was found to be more sensitive than
      sonography and almost as sensitive as CT in the detection of traumatic abdominal
      solid organ injuries. It can therefore be proposed as a useful tool in the
      assessment of blunt abdominal trauma.

PMID- 16632733
TI  - MRI of the peritoneum: spectrum of abnormalities.
AB  - OBJECTIVE: Our objective was to detail peritoneal anatomy, techniques for
      optimizing peritoneal MRI, and the MRI characteristics of several disease
      processes that frequently involve the peritoneum. CONCLUSION: Homogeneous fat
      suppression and dynamic contrast-enhanced imaging, including delayed imaging, are
      critical technical factors for successful lesion detection and characterization
      on peritoneal MRI.

PMID- 16632734
TI  - Occult colorectal polyps on CT colonography: implications for surveillance.
AB  - OBJECTIVE: Our purpose was to determine the prevalence of polyps that are
      invisible on CT colonography (CTC) in a population previously screened for
      colorectal neoplasms. Differences in the prevalence of occult polyps in various
      populations might help explain the discordant reported sensitivities for polyp
      detection in published reports of CTC. SUBJECTS AND METHODS: Seventy-five
      consecutive patients who had been previously screened for polyps underwent same
      day colonoscopy and CTC. Many of the patients had personal histories of previous
      polypectomies and were undergoing surveillance colonoscopy. The scans were
      interpreted prospectively by an experienced radiologist. Polyps missed
      prospectively on CTC were analyzed retrospectively by three experienced
      radiologists and categorized as perception errors (visible in retrospect),
      technical errors (e.g., obscured by feces or fluid), or occult (invisible).
      RESULTS: Thirty polyps 5 mm or larger were found at colonoscopy, 18 of which were
      missed prospectively on CTC. Of the 18 missed polyps, 12 could not be identified
      in retrospect, even though they were located in clean, dry, well-distended
      colonic segments. These were classified as occult. Ten of the 12 occult polyps
      showed flat morphology on review of colonoscopy video recordings. Of the
      remaining six missed polyps, two were classified as perception errors, two as
      technical errors, and two as a combination of technical and perception error.
      CONCLUSION: In this population, colonographically occult polyps were common and
      accounted for more detection failures than perception errors and technical errors
      combined. The high prevalence of occult polyps may be explained by the fact that
      previous screening may have led to removal of easy-to-see polyps, creating a
      study population with a higher percentage of hard-to-see polyps.

PMID- 16632735
TI  - Dynamic contrast-enhanced MRI of the bowel wall for assessment of disease
      activity in Crohn's disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of contrast
      enhanced dynamic MRI in predicting the disease activity of Crohn's disease.
      MATERIALS AND METHODS: Forty-eight patients in two hospitals who had clinically
      suspected exacerbation of Crohn's disease were included in this study. In three
      levels of thickened small-bowel wall, axial dynamic T1-weighted sequences were
      performed every 4-6 sec for a total duration of 2-3 min after contrast
      administration; static T1-weighted turbo spin-echo sequences were acquired both
      before and after contrast administration. The slope of enhancement, enhancement
      ratio, time to enhancement, enhancement time, and thickness of the small-bowel
      wall were determined. These MRI results were compared with overall clinical
      grade, Crohn's disease activity index (CDAI), and Van Hees activity index.
      Clinical grade was based on clinical information, physical findings, laboratory
      studies, endoscopy, surgery, and other imaging studies. Spearman's correlation
      coefficient and p values were determined per hospital. Fisher's z-transformation
      was applied before pooling the correlation coefficients from both hospitals.
      RESULTS: The enhancement ratio based on the static series showed significant
      correlation with the clinical grade (r = 0.29, p = 0.045), CDAI (r =0.31, p =
      0.033), and Van Hees activity index (r = 0.36, p = 0.016). The enhancement ratio
      based on the dynamic series correlated significantly with the CDAI (r = 0.38, p =
      0.016). Wall thickness correlated significantly with clinical grade (r = 0.47, p
      = 0.003) and Van Hees activity index (r = 0.41, p = 0.007). CONCLUSION: These
      data suggest that the enhancement ratio of bowel wall after IV administration of
      gadodiamide and bowel wall thickness are weak to moderate indicators of the
      severity of Crohn's disease.

PMID- 16632736
TI  - Colonic abnormalities on CT in adult hospitalized patients with Clostridium
      difficile colitis: prevalence and significance of findings.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of an
      abnormal colon on CT in adult inpatients with Clostridium difficile colitis,
      compare the clinical presentation of these patients, and determine whether CT
      findings predicted the need for surgical treatment. MATERIALS AND METHODS: Over a
      21-month period, 152 of 572 inpatients with C. difficile colitis were identified
      and had CT scans performed within 2 weeks of the diagnosis. These were
      independently and retrospectively reviewed by two reviewers. Those with colonic
      wall thickness greater than 4 mm were considered positive (CT-positive patients)
      and were further reviewed for specific findings in the colon. All 152 patients
      with CT scans were also retrospectively reviewed using the hospital information
      system for certain clinical parameters, admitting diagnoses, and reasons for
      scanning. The following were compared using several statistical tests: clinical
      parameters in CT-positive and CT-negative patients and surgical and nonsurgical
      groups to determine if positive scans or surgical treatment could be clinically
      predicted; specific CT findings in CT-positive patients to see if an association
      was found with clinical parameters or surgical treatment; and admitting diagnoses
      and reasons for scanning in scanned and unscanned populations to see which
      patients were more likely to undergo CT. RESULTS: Seventy-six (50%) of 152
      scanned hospitalized patients with C. difficile colitis were CT-positive. These
      patients most often had segmental involvement (50 [66%] of 76 patients), with the
      rectum (60 [82%] of 73 patients) and sigmoid colon (61 [82%] of 74 patients) most
      often affected. Positive scans were associated with increased WBC, abdominal
      pain, and diarrhea. Patients with signs and symptoms of infection or abdominal
      complaints were more likely to be scanned. No statistical correlation was found
      between specific CT findings and clinical parameters or clinical parameters and
      patients requiring surgery. There was no predictive value of specific CT findings
      for surgical treatment. CONCLUSION: Half of the patients scanned had an abnormal
      CT, with segmental colonic disease more common than diffuse. Positive scans were
      more likely in patients with leukocytosis, abdominal pain, and fever. Specific CT
      findings did not correlate with clinical parameters and could not predict
      surgical treatment.

PMID- 16632737
TI  - An algorithm for the diagnosis of focal liver masses using microbubble contrast
      enhanced pulse-inversion sonography.
AB  - OBJECTIVE: The objective of this study was to develop an algorithm for liver mass
      diagnosis using microbubble contrast-enhanced pulse-inversion sonography.
      SUBJECTS AND METHODS: Ninety-six lesions in 92 patients were evaluated with DMP
      115 (Definity)-enhanced pulse-inversion sonography, comprising 44 malignancies
      (29 hepatocellular carcinomas, 12 metastases, two peripheral cholangiocarcinomas,
      and one hepatic lymphoma) and 52 benign lesions (26 hemangiomas, 20 focal nodular
      hyperplasias, and six others). All had continuous low-mechanical-index imaging
      through the arterial and portal venous phase. A three-person blind review
      evaluated single images at baseline, early and peak arterial phases, and through
      the extended portal phases with a movie showing arterial phase wash-in. Reviewers
      assessed lesional vascularity and enhancement blindly but did not make a
      diagnosis. Combinations of answers were compared with independently determined
      final diagnoses to develop an algorithm for liver mass diagnosis. RESULTS: Portal
      phase enhancement comprises the first step of the algorithm, with positive or
      sustained enhancement identifying 48 (92%) of 52 benign lesions and negative
      enhancement or washout present in 41 (93%) of 44 malignancies. Sustained portal
      phase enhancement with arterial phase peripheral nodularity and centripetal
      progression predicted 24 (92%) of 26 of the hemangiomas; diffuse arterial phase
      enhancement greater than the liver identified 19 (95%) of 20 of the focal nodular
      hyperplasias. With negative portal phase enhancement, arterial phase information
      was less effective at differentiating hepatocellular carcinoma (25 [86%] of 29
      cases) from another hepatic malignancy (11 [73%] of 15 cases). CONCLUSION: A
      simple diagnostic algorithm for interpretation of microbubble-enhanced sonography
      provides sensitive and accurate diagnosis of commonly encountered liver masses.

PMID- 16632738
TI  - Effect of injection rate of contrast material on CT of hepatocellular carcinoma.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of two injection
      rates of contrast material (3 mL/sec and 5 mL/sec) in hepatic arterial dominant
      phase MDCT for the detection of small (< 2 cm) hepatocellular carcinomas.
      MATERIALS AND METHODS: The injection rates 3 mL/sec and 5 mL/sec were used
      prospectively in imaging examinations of patients with the suspected diagnosis of
      hepatocellular carcinoma. Each group consisted of 30 patients by chance. The
      group that received injections at 3 mL/sec had 35 hepatocellular carcinoma
      lesions, and the 5 mL/sec group had 41 lesions. In all patients the dose and
      concentration of contrast material were 100 mL and 350 mg/mL iodine (total dose
      of iodine, 35 g). In each patient a mini-test-bolus technique was used with an
      additional 15 mL of contrast material to determine optimal scan delay after
      administration of contrast material. Receiver operating characteristic analysis
      was used to assess diagnostic performance with the two injection rates of
      contrast material. RESULTS: There were no statistically significant differences
      between the two groups in regard to area under the curve and sensitivity. These
      values for the 3 mL/sec group were 0.97 and 28/35 (80%) and for the 5 mL/sec
      group were 0.96 and 36/41 (88%). However, the specificity and positive predictive
      values at 3 mL/sec (236/250 [95%] and 28/42 [67%]) were significantly higher than
      those at 5 mL/sec (227/265 [86%] and 36/73 [49%]) (p < 0.05). These results
      suggest there were more false-positive findings of contrast-enhanced lesions in
      cirrhotic livers on hepatic arterial dominant phase images obtained after
      injection of contrast material at 5 mL/sec than on images obtained after
      injection at 3 mL/sec. CONCLUSION: In the detection of small hypervascular
      hepatocellular carcinoma in cirrhotic liver, the risk of false-positive findings
      of lesions on hepatic arterial dominant phase images is significantly greater
      with the higher injection rate (5 mL/sec) than with the medium rate (3 mL/sec).

PMID- 16632739
TI  - Postprocedure sepsis in imaging-guided percutaneous hepatic abscess drainage: how
      often does it occur?
AB  - OBJECTIVE: This retrospective study was conducted to determine the incidence of
      sepsis at our institution after percutaneous drainage of a hepatic abscess.
      MATERIALS AND METHODS: Thirty-three patients with a hepatic abscess treated using
      percutaneous aspiration and drainage from 1995 to 2000 were identified from a
      search of the interventional database. The patients' charts and CT images were
      reviewed independently by two radiologists for clinical presentation, relevant
      medical history, pre- and postprocedure antibiotic regimens, and clinical course
      after percutaneous aspiration and drainage. The preprocedure images were reviewed
      for the location and morphology of the abscess. The procedure details including
      percutaneous approach, guidance technique, catheter size, and immediate
      postprocedure complications were reviewed. RESULTS: Of the 33 patients, 14
      patients underwent only needle aspiration of the abscess. In six (43%) of these
      14 patients, the abscesses resolved with aspiration and appropriate antibiotic
      treatment alone. Eight (57%) of the patients who had aspiration of the abscess
      initially went on to have drainage catheters placed within a 72-hr period.
      Nineteen patients had drainage catheters placed from the onset. Of these, 17
      patients (89%) had abscess resolution. Of the 27 patients who had catheters
      placed, a total of seven patients (26%) developed clinical symptoms of septicemia
      after catheter placement, but all patients, at least initially, responded to
      supportive treatment. Two patients died from septicemia 3-6 weeks after the
      procedure. None of the patients who underwent aspiration only developed
      postprocedure septicemia. CONCLUSION: After placement of a percutaneous drainage
      catheter in a hepatic abscess, there is a significant risk (26%) of postprocedure
      sepsis. Although it appears to be a random and unpredictable event in our small
      series, interventional radiologists and referring physicians should be aware of
      the risk of sepsis after percutaneous drainage of hepatic abscess.

PMID- 16632740
TI  - Dynamic CT Evaluation of Tumor Vascularity in Renal Cell Carcinoma.
AB  - OBJECTIVE: The purpose of our study was to evaluate the correlation between the
      enhancement parameters of dynamic CT; the carcinoma tissue microvessel density
      (MVD, a hotspot method to provide a histologic assessment of tumor vascularity);
      and tumor nuclear grade in renal cell carcinomas. SUBJECTS AND METHODS: Twenty
      four patients with histologically diagnosed renal cell carcinoma underwent
      dynamic enhanced CT. Enhancement parameters, slope of the time-density curve, the
      density difference before and after tissue enhancement (deltaH), tissue blood
      ratio (TBR), and area under the time-density curve (AR), were calculated for all
      lesions. Pathology slides corresponding to the CT plane were stained using mouse
      antihuman CD34 monoclonal antibody and H and E. Fuhrman nuclear grade was used.
      Vascular hot spots of microvessels were recorded. Spearman's rank correlation was
      performed to determine the strength of the relationship between enhancement
      parameters, MVD determinations, and tumor nuclear grade. RESULTS: MVD with CD34
      staining revealed uneven distribution of positively stained vascular endothelial
      cells in renal cell carcinoma lesions. Heterogeneous distribution of contrast
      enhancement was seen among and within individual tumors. The tumors appeared as
      uneven patterns on time-density curves of renal cell carcinoma lesions.
      Enhancement parameters of H (median, 21.0 H; range, 2.2-105.8 H), TBR (median,
      39%; range, 10.7-154.7%), AR (median, 1.58 H x sec; range, 0.23-3.67 H x sec),
      and slope (median, 2.76; range, 0.53-6.76) varied greatly. Renal cell carcinoma
      tissue MVD significantly correlated with all enhancement parameters of dynamic
      CT. The correlation coefficients (r) were 0.62, 0.54, 0.55, and 0.44,
      respectively, for delta H, slope, TBR, and AR (p < 0.0 5). All enhancement
      parameters did not significantly correlate with tumor nuclear grade. They were
      not predictive of nuclear grade. CONCLUSION: Enhancement parameters of dynamic CT
      may be suited to evaluate tumor vascularity in vivo. Dynamic enhanced CT images
      may reflect the heterogeneity of tumor angiogenesis on the basis of the
      correlation between enhancement parameters and MVD of renal cell carcinoma.

PMID- 16632741
TI  - Contrast-enhanced sonography for prostate cancer detection in patients with
      indeterminate clinical findings.
AB  - OBJECTIVE: The purpose of our study was to evaluate the usefulness of contrast
      enhanced sonography for prostate cancer detection in patients with an
      indeterminate prostate-specific antigen (PSA) level (4-10 ng/mL) and negative
      findings on digital rectal examination. SUBJECTS AND METHODS: Forty-eight
      patients underwent gray-scale, color Doppler, and contrast-enhanced sonography
      examinations and then sonographically guided biopsy. Contrast-enhanced sonography
      was performed using Levovist at a mechanical index of 1.1-1.4. The performances
      of the three methods for cancer detection were compared according to biopsy site
      and patient. RESULTS: Sensitivity by biopsy site was greater on contrast-enhanced
      sonography (68%) than on gray-scale (39%) and color Doppler (41%) sonography (p >
      or = 0.05), whereas the specificity and overall accuracy by biopsy site (82% and
      77% for gray-scale sonography, 84% and 79% for color Doppler sonography, and 83%
      and 81% for contrast-enhanced sonography, respectively) were not different for
      the three methods (p > 0.05). The concordance score for sonography and biopsy
      results by patient was not different for gray-scale (6.4 +/- 1.8), color Doppler
      (6.3 +/- 0.6), and contrast-enhanced sonography (6.5 +/- 0.7) (p = 0.281).
      CONCLUSION: Contrast-enhanced sonography could improve only the sensitivity for
      cancer detection in analysis by biopsy site but did not improve the overall
      performance of sonography in patients with an indeterminate PSA level and
      negative digital rectal examination.

PMID- 16632742
TI  - Time-resolved 3D MR angiography with parallel imaging for evaluation of
      hemodialysis fistulas and grafts: initial experience.
AB  - OBJECTIVE: We optimized a time-resolved 3D contrast-enhanced MR angiography
      sequence with integrated parallel imaging technique that can provide a large
      field of view with high temporal and spatial resolution, by which the
      hemodialysis access and the entire course of the inflow and outflow vessels can
      be imaged at a single anatomic station. Our objective was to evaluate the
      feasibility and usefulness of this method in the evaluation of patients referred
      for possible abnormalities in hemodialysis access. CONCLUSION: Time-resolved
      contrast-enhanced 3D MR angiography with parallel imaging has the potential to
      provide a rapid and comprehensive evaluation for the surveillance and diagnosis
      of hemodialysis access malfunctions. This technique may function as an important
      complement to conventional digital subtraction angiography and may be able to
      help guide medical management. The MR angiography protocol we present is a
      noninvasive, versatile, and time-efficient technique, without the need of direct
      graft puncture or flow interruption, and can be performed using a single
      injection of contrast material at a single station.

PMID- 16632743
TI  - Multiple cerebral microbleeds in hyperacute ischemic stroke: impact on prevalence
      and severity of early hemorrhagic transformation after thrombolytic treatment.
AB  - OBJECTIVE: The purpose of our study was to assess whether cerebral microbleeds
      are related to early hemorrhagic transformation after thrombolytic therapy for
      hyperacute ischemic stroke. MATERIALS AND METHODS: The cases of 279 patients with
      suspected ischemic stroke who underwent MRI including T2*-weighted images were
      retrospectively evaluated. The inclusion criteria were as follows: imaging
      performed within 6 hr after symptom onset, presence of territorial infarct of
      anterior circulation, no history of intracerebral hemorrhage, thrombolytic
      treatment, and available follow-up MR images. Microbleeds were classified
      according to number as follows: absent (grade 1, 0 bleeds), mild (grade 2, 1-2
      bleeds), moderate (grade 3, 3-10 bleeds), and severe (grade 4, > 10 bleeds). The
      prevalence and severity of early hemorrhagic transformation after thrombolysis
      were assessed on follow-up images. RESULTS: Among 279 patients, 65 patients (37
      men, 28 women; mean age, 67 years) met the inclusion criteria. Microbleeds were
      found in 25 patients. Early hemorrhagic transformation occurred in nine of 40
      patients without microbleeds (grade 1) and in eight of 25 patients with
      microbleeds: two of 12 patients with grade 2, three of eight patients with grade
      3, and three of five patients with grade 4 microbleeds. The presence of
      symptomatic hemorrhage did not correlate with the number of microbleeds. Results
      of multivariate logistic regression analysis showed that the presence of
      microbleeds was not associated with hemorrhagic transformation after thrombolytic
      treatment. CONCLUSION: Small and large numbers of microbleeds are not independent
      risk factors for early hemorrhagic transformation and symptomatic hemorrhage
      after thrombolytic therapy for hyperacute ischemic stroke. Additional studies
      with large groups of subjects are needed to confirm our conclusion.

PMID- 16632744
TI  - Quantitative analysis and effect of attenuation correction on lymph node staging
      of non-small cell lung cancer on SPECT and CT.
AB  - OBJECTIVE: The purpose of our study was to assess quantitative indexes and the
      effect of attenuation correction on the evaluation of lymph node metastasis in
      the staging of non-small cell lung cancer (NSCLC) using fused thallium-201
      SPECT/CT images. MATERIALS AND METHODS: We evaluated 156 lymph nodes (66
      metastatic, 90 nonmetastatic) from 29 patients with NSCLC. Using our combined
      SPECT/CT system, all patients underwent 201Tl SPECT and CT examinations
      immediately (early images) and 3 hr after (delayed images) the injection of
      201Tl. SPECT images were reconstructed with and without attenuation correction.
      For the quantitative evaluation of lymph node metastasis, we calculated the early
      ratio, the delayed ratio, and the washout ratio for SPECT images and the short
      axis diameter for CT images. Receiver operating characteristic (ROC) analysis was
      performed in each index for the differentiation between metastatic and
      nonmetastatic lymph nodes. Visual analysis was also performed by two experienced
      radiologists. RESULTS: The area under the ROC curve (A(z)) showed that early
      ratio and delayed ratio were superior to short-axis diameter for the assessment
      of lymph node metastasis. In addition, early and delayed ratios on attenuation
      corrected images were superior to those ratios on images without attenuation
      correction. However, the A(z) value for washout ratio was smaller than that for
      short-axis diameter. Early ratio on attenuation-corrected images was the most
      useful index (A(z) = 0.94). The sensitivity, specificity, and accuracy for early
      ratio on attenuation-corrected images were 78.8%, 94.4%, and 87.8% for the
      diagnosis of lymph node metastasis and 84.6%, 100%, and 93.1% for clinical
      staging (N0-N1 vs N2-N3), respectively. Fused images showed significantly higher
      diagnostic accuracy than CT images on visual analysis. CONCLUSION: Quantitative
      assessment using fused SPECT/CT images is useful for the diagnosis of lymph node
      metastasis in patients with NSCLC.

PMID- 16632745
TI  - Truncation artifact on PET/CT: impact on measurements of activity concentration
      and assessment of a correction algorithm.
AB  - OBJECTIVE: Discrepancy between fields of view (FOVs) in a PET/CT scanner causes a
      truncation artifact when imaging extends beyond the CT FOV. The purposes of this
      study were to evaluate the impact of this artifact on measurements of 18F-FDG
      activity concentrations and to assess a truncation correction algorithm.
      MATERIALS AND METHODS: Two phantoms and five patients were used in this study. In
      the first phantom, three inserts (water, air, bone equivalent) were placed in a
      water-filled cylinder containing 18F-FDG. In the second phantom study, a chest
      phantom and a 2-L bottle fitted with a bone insert were used to simulate a
      patient's torso and arm. Both phantoms were imaged while positioned centrally
      (baseline) and at the edge of the CT FOV to induce truncation. PET images were
      reconstructed using attenuation maps from truncated and truncation-corrected CT
      images. Regions of interest (ROIs) drawn on the inserts, simulated arm, and
      background water of the baseline truncated and truncation-corrected PET images
      were compared. In addition, extremity malignancies of five patients truncated on
      CT images were reconstructed with and without correction and the maximum standard
      uptake values (SUVs) of the malignancies were compared. RESULTS: Truncation
      artifact manifests as a rim of high activity concentration at the edge of the
      truncated CT image with an adjacent low-concentration region peripherally. The
      correction algorithm minimizes these effects. Phantom studies showed a maximum
      variation of -5.4% in the truncation-corrected background water image compared
      with the baseline image. Activity concentration in the water insert was 6.3%
      higher while that of air and bone inserts was similar to baseline. Extremity
      malignancies showed a consistent increase in the maximum SUV after truncation
      correction. CONCLUSION: Truncation affects measurements of 18F-FDG activity
      concentrations in PET/CT. A truncation-correction algorithm corrects truncation
      artifacts with small residual error.

PMID- 16632746
TI  - On the AJR viewbox. Ectopic pituitary adenoma with an empty sella.

PMID- 16632747
TI  - On the AJR viewbox. Hematometrocolpos due to imperforate hymen in a patient with
      bicornuate uterus.

PMID- 16632748
TI  - On the AJR viewbox. Hypereosinophilic syndrome presenting as a paravertebral
      mass.

PMID- 16632749
TI  - T. B. Harlem.

PMID- 16632750
TI  - The neglected global burden of chronic oral diseases.

PMID- 16632751
TI  - Porphyromonas gingivalis-epithelial cell interactions in periodontitis.
AB  - Emerging data on the consequences of the interactions between invasive oral
      bacteria and host cells have provided new insights into the pathogenesis of
      periodontal disease. Indeed, modulation of the mucosal epithelial barrier by
      pathogenic bacteria appears to be a critical step in the initiation and
      progression of periodontal disease. Periodontopathogens such as Porphyromonas
      gingivalis have developed different strategies to perturb the structural and
      functional integrity of the gingival epithelium. P. gingivalis adheres to,
      invades, and replicates within human epithelial cells. Adhesion of P. gingivalis
      to host cells is multimodal and involves the interaction of bacterial cell
      surface adhesins with receptors expressed on the surfaces of epithelial cells.
      Internalization of P. gingivalis within host cells is rapid and requires both
      bacterial contact-dependent components and host-induced signaling pathways. P.
      gingivalis also subverts host responses to bacterial challenges by inactivating
      immune cells and molecules and by activating host processes leading to tissue
      destruction. The adaptive ability of these pathogens that allows them to survive
      within host cells and degrade periodontal tissue constituents may contribute to
      the initiation and progression of periodontitis. In this paper, we review current
      knowledge on the molecular cross-talk between P. gingivalis and gingival
      epithelial cells in the development of periodontitis.

PMID- 16632752
TI  - Osteopontin and mucosal protection.
AB  - Protection of mucosal tissues of the oral cavity, intestines, respiratory tract,
      and urogenital tract from the constant challenge of pathogens is achieved by the
      combined barrier function of the lining epithelia and specialized immune cells.
      Recent studies have indicated that osteopontin (OPN) has a pivotal role in the
      development of immune responses and in the tissue destruction and the subsequent
      repair processes associated with inflammatory diseases. While expression of OPN
      is increased in immune cells--including neutrophils, macrophages, T- and B
      lymphocytes--and in epithelial, endothelial, and fibroblastic cells of inflamed
      tissues, deciphering the specific functions of OPN has been difficult. In part,
      this is due to the broad range of biological activities of OPN that are mediated
      by multiple receptors which recognize several signaling motifs whose activities
      are influenced by post-translational modifications and proteolytic processing of
      OPN. Understanding the role of OPN in mucosal inflammation is further complicated
      by its contributions to the barrier function of the lining epithelia and the
      complexity of the specialized mucosal immune system. In an attempt to provide
      some insights into the involvement of OPN in mucosal diseases, this review
      summarizes current knowledge of the biological activities of OPN involved in the
      development of inflammatory responses and in wound healing, and indicates how
      these activities may affect the protection of mucosal tissues.

PMID- 16632753
TI  - Bone marrow cells can give rise to ameloblast-like cells.
AB  - Post-eruptive loss of ameloblasts requires identification of alternative sources
      for these cells to realize tooth-tissue-engineering strategies. Recent reports
      showed that bone-marrow-derived cells can give rise to different types of
      epithelial cells, suggesting their potential to serve as a source for
      ameloblasts. To investigate this potential, we mixed c-Kit(+)-enriched bone
      marrow cells with embryonic dental epithelial cells and cultured them in re
      association with dental mesenchyme. Non-dividing, polarized, and secretory
      ameloblast-like cells were achieved without cell fusion. Before basement membrane
      reconstitution, some bone marrow cells migrated to the mesenchyme, where they
      exhibited morphological, molecular, and functional characteristics of
      odontoblasts. These results show, for the first time, that bone-marrow-derived
      cells can be reprogrammed to give rise to ameloblast-like cells, offering novel
      possibilities for tooth-tissue engineering and the study of the simultaneous
      differentiation of one bone marrow cell subpopulation into cells of two different
      embryonic lineages.

PMID- 16632754
TI  - Hydrolysis of functional monomers in a single-bottle self-etching primer-
      correlation of 13C NMR and TEM findings.
AB  - Self-etching primers/adhesives that combine acidic methacrylate monomers with
      water in a single bottle are hydrolytically unstable and require refrigeration to
      extend their shelf-lives. This study tested the null hypothesis that one year of
      intermittent refrigeration of a 4-MET-containing simplified self-etching primer
      does not result in hydrolytic changes that are identifiable by transmission
      electron microscopy and (13)C NMR spectroscopy. Human dentin was bonded with
      UniFil Bond immediately after being unpacked, or after one year of intermittent
      refrigeration at 4 degrees C. Fresh and aged primers were analyzed by NMR for
      chemical changes. Ultrastructural observations indicated that there was an
      augmentation in etching capacity of the aged adhesive that was not accompanied by
      resin infiltration or effective polymerization. New NMR peaks detected from the
      aged ethanol-based primer confirmed that degradation occurred initially via
      esterification with ethanol, followed by hydrolysis of both ester groups in the 4
      MET. Hydrolysis of functional methacrylate monomers occurs despite intermittent
      refrigeration.

PMID- 16632755
TI  - Sonic hedgehog signaling is important in tooth root development.
AB  - Hertwig's epithelial root sheath (HERS) is important for tooth root formation,
      but the molecular basis for the signaling of root development remains uncertain.
      We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS
      function, because it mediates epithelial-mesenchymal interactions during
      embryonic odontogenesis. We examined the gene expression patterns of Shh
      signaling in murine developing molar roots. Shh and Patched2 transcripts were
      identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in
      the proliferative dental mesenchyme in addition to the HERS. To confirm whether
      Shh signaling physiologically functions in vivo, we analyzed mesenchymal
      dysplasia (mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In
      the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover,
      the molar eruption was disturbed, and all roots were shorter than those in
      control littermates at 4 wks. These results indicate that Shh signaling is
      important in tooth root development. Abbreviations used: BrdU, 5-bromo-2'
      deoxyuridine; HERS, Hertwig's epithelial root sheath; NFI-C/CTF, nuclear factor
      Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc,
      patched; Shh, sonic hedgehog; Smo, smoothened.

PMID- 16632756
TI  - Responses of rat pulp cells to heat stress in vitro.
AB  - Although heat stress can cause irritation in the dentin/pulp complex, little is
      known about the thermotolerance of pulp cells and their response to heat stress.
      We investigated cultured rat pulp cell responses to heat stress. Cells were
      subjected to a temperature of 42 degrees C for 30 minutes, and HSPs, alkaline
      phosphatase activity, and gap-junctional communication were determined at various
      time points. Although only low levels of HSP70 expression were detected before
      heat treatment, heat shock markedly induced HSP70 expression, with it gradually
      increasing at 1 hour after being heated. HSP25, however, showed no dramatic
      change. Gap junction protein connexin43 rapidly degraded after heat treatment,
      recovering to normal levels within the following 6 hours. Alkaline phosphatase
      activity decreased immediately after heat stress, recovering after 1 hour. These
      results indicate that dental pulp possesses protective factors, including HSPs,
      and that it can recover viability of intercellular communication and alkaline
      phosphatase activity after heat stress.

PMID- 16632757
TI  - Activation of iCaspase-9 in neovessels inhibits oral tumor progression.
AB  - Tumors of the oral cavity are highly vascularized malignancies. Disruption of
      neovascular networks was shown to limit the access of nutrients and oxygen to
      tumor cells and inhibit tumor progression. Here, we evaluated the effect of the
      activation of an artificial death switch (iCaspase-9) expressed in neovascular
      endothelial cells on the progression of oral tumors. We used biodegradable
      scaffolds to co-implant human dermal microvascular endothelial cells stably
      expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase
      (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively,
      untransduced HDMEC were co-implanted with oral cancer cells, and a
      transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to
      deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence
      demonstrated that tumor progression was inhibited, and immunohistochemistry
      showed that microvessel density was decreased, when iCaspase-9 was activated in
      tumor-associated microvessels. We conclude that activation of iCaspase-9 in
      neovascular endothelial cells is sufficient to inhibit the progression of
      xenografted oral tumors.

PMID- 16632758
TI  - Edema in oral mucosa after LPS or cytokine exposure.
AB  - Lowering of interstitial fluid pressure (P(if)) is an important factor that
      explains the rapid edema formation in acute inflammation in loose connective
      tissues. Lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are pathogenetic in
      gingivitis. To test if these substances induce lowering of P(if) in rat oral
      mucosa, we measured P(if) with a micropuncture technique. IL-1beta and TNF-alpha
      caused lowering of P(if), whereas LPS induced an immediate increase in P(if),
      followed by lowering after 40 min. Measurements of fluid volume distribution
      showed a significant change in interstitial fluid volume (V(i)) 1.5 hr after LPS
      exposure as V(i) changed from 0.41 +/- 0.02 to 0.51 +/- 0.03 mL/g wet weight (p <
      0.05), confirming edema. These findings show that LPS, IL-1beta, and TNF-alpha
      induce lowering of P(if) in the rat oral mucosa and contribute to edema formation
      in LPS-induced gingivitis.

PMID- 16632759
TI  - Regulation of PLAP-1 expression in periodontal ligament cells.
AB  - Periodontal-ligament-associated protein-1 (PLAP-1) is preferentially expressed in
      the periodontal ligament (PDL) and encodes a novel small leucine-rich repeat
      proteoglycan protein. PLAP-1 expression was induced during the course of
      cytodifferentiation of PDL cells into mineralized-tissue-forming cells in vitro,
      suggesting the possible involvement of PLAP-1 in the mineralization process of
      PDL cells. In this study, we hypothesized that PLAP-1 expression is regulated by
      mineralization-related cytokines in PDL cells. PLAP-1 expression was clearly down
      regulated when the cytodifferentiation of PDL cells was reversibly inhibited by
      fibroblast growth factor-2 (FGF-2). In contrast, bone morphogenetic protein-2
      (BMP-2) enhanced PLAP-1 expression. Up-regulation of PLAP-1 expression by BMP-2
      was confirmed at the protein level when PDL cells were immunostained with anti
      PLAP-1 polyclonal antibody. These results revealed the cytokine-mediated
      regulatory mechanisms of PLAP-1 expression and suggested that PLAP-1 expression
      may be associated with the process of cytodifferentiation of PDL cells.

PMID- 16632760
TI  - Accumulation of non-steroidal anti-inflammatory drugs by gingival fibroblasts.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and
      inflammatory disorders. We hypothesized that gingival fibroblasts actively
      accumulate NSAIDs and enhance their levels in gingival connective tissue. Using
      fluorescence to monitor NSAID transport, we demonstrated that cultured gingival
      fibroblasts transport naproxen in a saturable, temperature-dependent manner with
      a K(m) of 127 mug/mL and a V(max) of 1.42 ng/min/mug protein. At steady state,
      the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2
      for ibuprofen. Naproxen transport was most efficient at neutral pH and was
      significantly enhanced upon cell treatment with TNF-alpha. In humans,
      systemically administered naproxen attained steady-state levels of 61.9 mug/mL in
      blood and 9.4 mug/g in healthy gingival connective tissue, while ibuprofen
      attained levels of 2.3 mug/mL and 1.5 mug/g, respectively. Thus, gingival
      fibroblasts possess transporters for NSAIDs that are up-regulated by an
      inflammatory mediator, but there is no evidence that they contribute to elevated
      NSAID levels in healthy gingiva.

PMID- 16632761
TI  - Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis
      through OPG induction.
AB  - The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under
      mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic
      alveolar bone resorption. Previously, we discovered that continuous compressive
      force on PDL cells induced osteoclastogenesis-supporting activity, with up
      regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile
      force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and
      does not induce osteoclastogenesis-supporting activity. PDL cells were
      mechanically stimulated by cyclical tensile force in vitro. The conditioned media
      of PDL cells that had been subjected to cyclical tensile force inhibited
      osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA
      expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated
      TGF-beta expression in PDL cells as well. Administration of neutralizing
      antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force
      stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis
      inhibitory effect of the conditioned media of PDL cells under cyclical tensile
      force was partially rescued by the administration of TGF-beta neutralizing
      antibodies. In conclusion, tensile force inhibited the osteoclastogenesis
      supporting activity of PDL cells by inducing the up-regulation of OPG via TGF
      beta stimulation.

PMID- 16632762
TI  - Nutrition counseling increases fruit and vegetable intake in the edentulous.
AB  - Edentulous denture-wearers eat fewer fruits and vegetables than do comparable
      dentate individuals. Improved chewing ability with new dentures has resulted in
      little dietary improvement, suggesting that dietary intervention is necessary.
      The objective of this randomized controlled trial was to have a positive impact
      upon dietary behavior of patients receiving replacement complete dentures through
      a tailored dietary intervention. Readiness to change diet (Stage of Change),
      intake of fruits, vegetables, and nutrients, and chewing ability were assessed
      pre-and 6 weeks post-intervention. The intervention group (n = 30) received two
      dietary counseling sessions; the control group (n = 28) received current standard
      care. Perceived chewing ability significantly increased in both groups. There was
      significantly more movement from pre-action into action Stages of Change in the
      intervention group, who had a greater increase in fruit/vegetable consumption
      (+209 g/d) than did the control group (+26 g/d) (P = 0.001). Tailored dietary
      intervention contemporaneous with replacement dentures can positively change
      dietary behavior.

PMID- 16632763
TI  - Caries-inhibiting effect of chlorhexidine varnish in pits and fissures.
AB  - Evidence regarding the caries-inhibiting effect of chlorhexidine varnish is
      inconclusive. This study investigated the caries-inhibiting effect of the varnish
      EC40 on pits and fissures of first permanent molars. A two-year randomized
      controlled trial was carried out among 461 six- to seven-year-old children. In a
      split-mouth design, one group of molars received EC40 at baseline, 6, 12, and 18
      months, and another group at baseline, 3, 12, and 15 months. Control molars did
      not receive EC40. Adherence to the treatment protocol was good. The dropout rate
      was 17%. Blinded examiners performed dental examinations. The caries-inhibiting
      effects of the two EC40 application schemes were comparable. The prevented
      fraction of caries was 25% (95%CI, 1%, 49%, p = 0.04) after 2 years and 9%
      (95%CI, -11%, 29%, p = 0.20) one year after termination of the trial, suggesting
      a short-term benefit from the use of EC40. The efficiency of EC40 is questionable
      in low-caries-incidence child populations.

PMID- 16632764
TI  - Peri-implant inflammation defined by the implant-abutment interface.
AB  - An implant-abutment interface at the alveolar bone crest is associated with
      sustained peri-implant inflammation; however, whether magnitude of inflammation
      is proportionally dependent upon interface position remains unknown. This study
      compared the distribution and density of inflammatory cells surrounding implants
      with a supracrestal, crestal, or subcrestal implant-abutment interface. All
      implants developed a similar pattern of peri-implant inflammation: neutrophilic
      polymorphonuclear leukocytes (neutrophils) maximally accumulated at or
      immediately coronal to the interface. However, peri-implant neutrophil accrual
      increased progressively as the implant-abutment interface depth increased, i.e.,
      subcrestal interfaces promoted a significantly greater maximum density of
      neutrophils than did supracrestal interfaces (10,512 +/- 691 vs. 2398 +/- 1077
      neutrophils/mm(2)). Moreover, inflammatory cell accumulation below the original
      bone crest was significantly correlated with bone loss. Thus, the implant
      abutment interface dictates the intensity and location of peri-implant
      inflammatory cell accumulation, a potential contributing component in the extent
      of implant-associated alveolar bone loss.

PMID- 16632765
TI  - Who's speaking?

PMID- 16632766
TI  - Letter to the editors.

PMID- 16632768
TI  - Authentic leaders creating healthy work environments for nursing practice.
AB  - Implementation of authentic leadership can affect not only the nursing workforce
      and the profession but the healthcare delivery system and society as a whole.
      Creating a healthy work environment for nursing practice is crucial to maintain
      an adequate nursing workforce; the stressful nature of the profession often leads
      to burnout, disability, and high absenteeism and ultimately contributes to the
      escalating shortage of nurses. Leaders play a pivotal role in retention of nurses
      by shaping the healthcare practice environment to produce quality outcomes for
      staff nurses and patients. Few guidelines are available, however, for creating
      and sustaining the critical elements of a healthy work environment. In 2005, the
      American Association of Critical-Care Nurses released a landmark publication
      specifying 6 standards (skilled communication, true collaboration, effective
      decision making, appropriate staffing, meaningful recognition, and authentic
      leadership) necessary to establish and sustain healthy work environments in
      healthcare. Authentic leadership was described as the "glue" needed to hold
      together a healthy work environment. Now, the roles and relationships of
      authentic leaders in the healthy work environment are clarified as follows: An
      expanded definition of authentic leadership and its attributes (eg, genuineness,
      trustworthiness, reliability, compassion, and believability) is presented.
      Mechanisms by which authentic leaders can create healthy work environments for
      practice (eg, engaging employees in the work environment to promote positive
      behaviors) are described. A practical guide on how to become an authentic leader
      is advanced. A research agenda to advance the study of authentic leadership in
      nursing practice through collaboration between nursing and business is proposed.

PMID- 16632769
TI  - Levels of care in the intensive care unit: a research program.
AB  - A multidisciplinary research program on levels of care was conducted in 15 adult
      intensive care units in North America, Europe, and Australia. The program
      addressed advance directives for cardiopulmonary resuscitation, provision of
      advanced life support, and clinicians' discomfort with evolving treatment plans.
      The results indicated that the factors that determined the establishment of
      directives for advance life support differed from the factors that informed a
      decision to limit or withdraw support after admission to an intensive care unit.
      In addition, clinicians' prognoses were imprecise and often an underestimation of
      the probability of short-term survival. Finally, some degree of discomfort was
      common in care providers in the intensive care unit, most often because they
      thought interventions were excessive and not compatible with an acceptable future
      quality of life. The provision of advanced life support mandates explicit
      decision making about how life-support measures should be used.

PMID- 16632770
TI  - Elevated cardiac troponin levels in critically ill patients: prevalence,
      incidence, and outcomes.
AB  - BACKGROUND: Levels of cardiac troponin, a sensitive and specific marker of
      myocardial injury, are often elevated in critically ill patients. OBJECTIVES: To
      document elevated levels of cardiac troponin I in patients in a medical-surgical
      intensive care unit and the relationship between elevated levels and
      electrocardiographic findings and mortality. METHODS: A total of 198 patients
      expected to remain in the intensive care unit for at least 72 hours were
      classified as having myocardial infarction (cardiac troponin I level >or=1.2
      microg/L and ischemic electrocardiographic changes), elevated troponin level only
      (>or=1.2 microg/L and no ischemic electrocardiographic changes), or normal
      troponin levels. Events were classified as prevalent if they occurred within 48
      hours after admission and as incident if they occurred 48 hours or later after
      admission. Factors associated with mortality were examined by using regression
      analysis. RESULTS: A total of 171 patients had at least one troponin level
      measured in the first 48 hours. The prevalence of elevated troponin level was
      42.1% (72 patients); 38 patients (22.2%) had myocardial infarction, and 34
      (19.9%) had elevated troponin level only. After the first 48 hours, 136 patients
      had at least 1 troponin measurement. The incidence of elevated troponin level was
      11.8% (16 patients); 7 patients (5.1%) met criteria for myocardial infarction,
      and 2 (1.5%) had elevated troponin level only. Elevated levels of troponin I at
      any time during admission were associated with mortality in the univariate but
      not the multivariate analysis. CONCLUSIONS: Elevated levels of cardiac troponin I
      in critically ill patients do not always indicate myocardial infarction or an
      adverse prognosis.

PMID- 16632771
TI  - Correlates of neurocognitive function of patients after off-pump coronary artery
      bypass surgery.
AB  - BACKGROUND: Decreases in neurocognitive function have been reported in patients
      who have undergone off-pump coronary artery bypass surgery; however, few
      investigators have examined the correlates of the decreases. OBJECTIVES: To
      explore and determine the correlates of neurocognitive function at the time of
      discharge from the hospital in patients undergoing off-pump coronary artery
      bypass surgery. METHODS: Patients undergoing off-pump coronary artery bypass
      surgery at Abbott Northwestern Hospital, Minneapolis, Minn, were administered
      tests of neuro-cognition (cognition and motor function), anxiety, depression, and
      quality of life preoperatively (within 72 hours of surgery) and postoperatively
      (at least 72 hours after surgery but before discharge from the hospital).
      RESULTS: A total of 54 patients (79.6% men), mean age 64.5 years, completed tests
      both preoperatively and postoperatively. When baseline function was controlled
      for, increased age and new-onset atrial fibrillation (F(3,40)=42.97; P<.001) were
      associated with decreases in postoperative cognitive function; increased age and
      anxiety (F(3,35)=15.83; P<.001) were associated with decreases in postoperative
      motor function. CONCLUSION: Older patients, anxious patients, and patients with
      new-onset atrial fibrillation are at risk for neurocognitive changes after off
      pump coronary artery bypass surgery. Further studies with larger sample sizes
      should be done to examine interventions to reduce preoperative anxiety in these
      patients. Interventions to prevent postoperative atrial fibrillation should be
      explored to determine whether the interventions prevent a decline in
      neurocognitive function.

PMID- 16632772
TI  - Improving adherence to a mechanical ventilation weaning protocol for critically
      ill adults: outcomes after an implementation program.
AB  - BACKGROUND: Despite multiple reminders, education sessions, and multidisciplinary
      team involvement, adherence to an evidence-based mechanical ventilation weaning
      protocol had been less than 1% in a general systems intensive care unit since
      implementation. OBJECTIVE: To assess the effectiveness of using an implementation
      program, the Model for Accelerating Improvement, to improve adherence and
      clinical outcomes after restarting a mechanical ventilation weaning protocol in
      an adult general systems intensive care unit. METHODS: A prospective comparative
      design, before and after implementation of the Model for Accelerating
      Improvement, was used with a consecutive sample of 129 patients and 112
      multidisciplinary team members. Clinical outcomes were rate of unsuccessful
      extubations, rate of ventilator-associated pneumonia, and duration of mechanical
      ventilation; practice outcomes were staff's understanding of the mechanical
      ventilation weaning protocol, perceptions of the practice safety climate, and
      adherence to the weaning protocol. RESULTS: After the intervention, the rate of
      unsuccessful extubations decreased, and staff's understanding of and adherence to
      the weaning protocol increased significantly. The rate of ventilator-associated
      pneumonia, duration of mechanical ventilation, and staff's perceptions of the
      practice safety climate did not change significantly. CONCLUSION: Implementing
      the Model for Accelerating Improvement improved understanding of and adherence to
      protocol-directed weaning and reduced the rate of unsuccessful extubations.

PMID- 16632773
TI  - Electrocardiographic artifact mimicking ventricular tachycardia during high
      frequency oscillatory ventilation: a case report.

PMID- 16632774
TI  - Questions concerning the goodness of hastening death.

PMID- 16632775
TI  - Coronary endothelium: a key to life expectancy.

PMID- 16632776
TI  - Differentiating ST-Segment Strain Pattern From Acute Ischemia.

PMID- 16632779
TI  - Sonographic differential diagnosis of acute scrotum: real-time whirlpool sign, a
      key sign of torsion.
AB  - OBJECTIVE: The purpose of this study was to prospectively investigate the role of
      high-resolution and color Doppler sonography in the differential diagnosis of
      acute scrotum and testicular torsion in particular. METHODS: Patients who
      underwent sonography for acute scrotum between April 2000 and September 2005 were
      included in the study. Gray scale and color Doppler sonography of the scrotum was
      performed. The spermatic cord was studied on longitudinal and transverse scans
      from the inguinal region up to the testis, and the whirlpool sign was looked for.
      RESULTS: During this period, 221 patients underwent sonography for acute scrotum.
      Sixty-five had epididymo-orchitis with a straight spermatic cord, a swollen
      epididymis, testis, or both, an absent focal lesion in the testis, and increased
      flow on color Doppler studies along with the clinical features of infection.
      Three had testicular abscesses. Sonography revealed features of torsion of
      testicular appendages in 23 patients and acute idiopathic scrotal edema in 19.
      Complete torsion was seen in 61 patients who had the whirlpool sign on gray scale
      imaging and absent flow distal to the whirlpool. There was incomplete torsion in
      4 patients in whom the whirlpool sign was seen on both gray scale and color
      Doppler imaging. Nine patients had segmental testicular infarction, and 1 had a
      torsion-detorsion sequence revealing testicular hyperemia. In 14 patients, the
      findings were equivocal. There was a complicated hydrocele, mumps orchitis, and
      vasculitis of Henoch-Schonlein purpura in 1 patient each. Five patients had
      normal findings. Fourteen were lost for follow-up. CONCLUSIONS: Sonography of
      acute scrotum should include study of the spermatic cord. The sonographic real
      time whirlpool sign is the most specific and sensitive sign of torsion, both
      complete and incomplete. Intermittent testicular torsion is a challenging
      clinical condition with a spectrum of clinical and sonographic features.

PMID- 16632780
TI  - Doppler sonographic evaluation of hemodynamic changes in colorectal liver
      metastases relative to liver size.
AB  - OBJECTIVE: The mechanisms of hemodynamic alterations in colorectal liver
      metastases are not clearly understood yet. Considering that an increase in liver
      size in patients with metastases could also result in an alteration in total
      liver flow, we aimed to analyze hemodynamic changes relative to the liver volume
      and to search for the possibility of any intrinsic factors affecting blood flow
      in patients with metastases. METHODS: Twenty-eight patients with colorectal liver
      metastases and 20 control subjects with no liver disease were evaluated
      sonographically. All patients were examined prospectively by Doppler sonography
      and helical computed tomography. Hepatic hemodynamic parameters, including blood
      flow in the hepatic artery and portal vein, total blood flow to the liver, and
      Doppler perfusion index, were calculated, and values relative to liver volume
      were obtained. Hepatic perfusion changes in liver metastases were then compared
      with those in a control group. RESULTS: The liver volume of the patients with
      liver metastases was greater than that of the control group (P=.003). Hepatic
      arterial blood flow rates were higher, whereas portal flow rates were lower, in
      patients with liver metastases compared with control subjects (P<.05). Total
      liver blood flow was not significantly different between the two groups. However,
      total blood flow relative to liver volume was significantly lower in the
      metastatic group (P<.001). Doppler perfusion index values in the patients with
      metastasis were significantly higher than in the control group (P=.000).
      CONCLUSIONS: Our findings may support the hypothesis that a humoral mediator
      induced portal venous flow reduction causes perfusion changes in liver metastases
      from colorectal disease. However, an additional intrinsic hepatic hemodynamic
      event should also be present. Doppler perfusion index measurements can provide
      additional information in the evaluation of patients with colorectal liver
      metastases.

PMID- 16632781
TI  - Relationship of skeletal muscle perfusion measured by contrast-enhanced
      ultrasonography to histologic microvascular density.
AB  - OBJECTIVE: The purpose of this study was to compare skeletal muscle perfusion
      measured by contrast-enhanced ultrasonography (CEUS) with microvascular density
      in muscle biopsies. METHODS: Power Doppler sonography after intravenous bolus
      injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to
      examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local
      blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by
      analyzing replenishment kinetics. CEUS perfusion was compared with
      vascularization of biopsy samples from vastus lateralis muscle. Subjects were
      selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per
      body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large
      variability of skeletal muscle capillarization. Moreover, subjects' venous blood
      hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume
      fraction (1-Hkt=PVF) in which the microbubbles can distribute. RESULTS: Median
      capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary
      fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max
      (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC
      (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was
      r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus
      lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3]
      approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(
      1) . 100 g tissue(-1)). CONCLUSIONS: B is significantly related to fiber-adjacent
      capillarization and may represent physiologic capillary recruitment (eg, through
      metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion
      quantification.

PMID- 16632782
TI  - The value of sonography with micro convex probes in diagnosing meniscal tears
      compared with arthroscopy.
AB  - OBJECTIVE: Meniscal tears are common in knee injuries. Sonography has been used
      in the knee to evaluate meniscal tears. Linear probes with high resolution have
      been used, and the overall accuracy of sonography has been more than 70% in many
      studies. In this study, we used a 6.5-MHz micro convex probe to evaluate meniscal
      tears, and the results were compared with arthroscopic findings. METHODS: Four
      hundred six knee joints with knee pain and a clinical indication for arthroscopy
      were examined from the popliteal fossa with the 6.5-MHz micro convex probe. Those
      patients with positive sonographic findings who had an arthroscopic examination
      (100 patients) were included in our study, and the results were compared. The
      results were statistically analyzed by the Fisher exact test. RESULTS: One
      hundred knees with sonographic examinations underwent arthroscopic evaluation.
      Three age groups were included in the study (20-30, 30-40, and >40 years).
      Comparison of the results between the two methods showed sensitivity of 100% and
      specificity of 95% for sonography in detecting meniscal tears. The positive
      predictive value for the medial meniscus was 95%, and the negative predictive
      value was 100%; these values for the lateral meniscus were 93% and 100%,
      respectively. CONCLUSIONS: Meniscal tears are common in all age groups. The use
      of sonography allows rapid, low-cost, and noninvasive exploration of meniscal
      tears as a first-line diagnostic method. We recommend high-resolution micro
      convex probes, which better fit the anatomic concavity of the popliteal fossa, as
      efficient investigation tools.

PMID- 16632783
TI  - Pulsatility index at the cervical internal carotid artery as a parameter of
      microangiopathy in patients with type 2 diabetes.
AB  - OBJECTIVE: Although carotid intima-media thickness is a well-recognized indicator
      of atherosclerosis, it may not be an appropriate indicator of microangiopathy. We
      evaluated the parameters of extracranial carotid artery (CA) duplex
      ultrasonographic scanning in relation to microalbuminuria, which is an indicator
      of microangiopathy in patients with diabetes. The relationships of CA stenosis,
      hypertension, and dyslipidemia with microalbuminuria were also evaluated.
      METHODS: Among 234 patients who were hospitalized for controlling type 2 diabetes
      during a 20-month period, those with major cerebrovascular, cardiac, or renal
      disease were excluded, leaving 159 patients who did not have any acute symptoms
      enrolled in this cross-sectional study. The parameters of extracranial CA duplex
      ultrasonographic scanning and urine albumin-to-creatinine ratio (u-ACR) were
      extracted, and their relationships were analyzed. Each patient's status with
      regard to CA stenosis, hypertension, and dyslipidemia was also examined for the
      effects on u-ACR. RESULTS: Of the 159 patients, 29 (18.2%) had some CA stenosis,
      and there were significantly more hypertensive patients in this group (P=.007).
      The value of u-ACR was significantly higher in patients with dyslipidemia
      (P<.001) but not in those with CA stenosis or hypertension. With univariate
      analysis, significant correlations of u-ACR were observed with age, right end
      diastolic velocity, and the bilateral pulsatility index (PI). Among these
      factors, multivariate analysis was made, and only age and PI proved to be
      independent factors correlated with u-ACR (P<.0001). With a PI cutoff of 1.15,
      89.3% specificity with 49.1% sensitivity was obtained for detecting
      microalbuminuria. CONCLUSIONS: The PI at the cervical internal CA can indicate
      microangiopathy because of its strong correlation with microalbuminuria in
      patients with type 2 diabetes, and it is thought to reflect the microangiopathy
      of cerebral vessels.

PMID- 16632784
TI  - The Z technique: an easy approach to the display of the mid-coronal plane of the
      uterus in volume sonography.
AB  - OBJECTIVE: The purpose of our study was to evaluate the ease of learning and
      clinical applicability of a technique (Z technique) for display of the mid
      coronal plane of the uterus in volume sonography. METHODS: Eight physicians were
      randomly assigned to 2 groups, A and B, after being instructed on the basic
      principles of post processing of sonographic volumes. Physicians in group A were
      asked to individually display the mid-coronal plane of the uterus in each of five
      3-dimensional volumes of uteri. Physicians in group B were instructed on the Z
      technique and were then asked to individually display the mid-coronal plane of
      the uterus in the same volumes as group A. The time needed for display of the mid
      coronal plane of the uterus and the quality of the mid-coronal plane image
      retrieved were recorded for each volume. RESULTS: The mean time required to
      display the mid-coronal plane of the uterus for all volumes was 47.7 seconds in
      group B compared with 110.7 seconds in group A (P=.002). Furthermore, a
      significant improvement in time performance was seen for physicians in group A
      after learning the Z technique (23.2 seconds after compared with 110.7 seconds
      before; P=.0001). The quality of the image produced was notably better for all
      physicians after learning the Z technique. CONCLUSIONS: The Z technique is an
      easy technique to learn. Physicians who learn this technique are able to retrieve
      the mid-coronal plane of the uterus faster and improve its image quality in
      volume sonography.

PMID- 16632785
TI  - The shadow of the intrauterine device.
AB  - OBJECTIVE: An intrauterine device (IUD) is a highly effective and prevalent form
      of birth control with a low failure rate. It is not without complications,
      including irregular bleeding and pelvic pain, perforation, expulsion, and
      pregnancy. Investigation of the symptomatic patient and routine follow-up of
      asymptomatic women with IUDs include transvaginal ultrasonography to rule out IUD
      malposition and other complications. Three-dimensional ultrasonography (3DUS) has
      been shown to have added value in imaging the pelvic organs, including the
      uterus. However, even with 3DUS, the operator may encounter difficulty in imaging
      the IUD in its entirety, because of variability in both echogenicity and exact
      location. METHODS: More than 30 women undergoing IUD placement evaluation,
      including routine examinations and cases of suspected pregnancy, irregular
      bleeding, infection, and pelvic pain, were evaluated with 3DUS and volume
      contrast imaging in the C plane (VCI-C), which visualized acoustic shadows of the
      IUDs, facilitating identification of the intrauterine position and type of the
      device. RESULTS: Four examples are presented from women undergoing evaluation of
      IUD placement in whom 2-dimensional ultrasonography failed to visualize the
      device satisfactorily. Volume contrast imaging in the C plane allowed
      visualization of the acoustic shadows of the IUDs, thereby providing more exact
      imaging of the type of device as well as aiding in locating the IUD. In a woman
      with irregular bleeding, a bicornuate uterus with pregnancy in 1 horn and a bowed
      T-type IUD in the contralateral horn were diagnosed with VCI-C. CONCLUSIONS: We
      conclude from these shadow images that VCI-C is a useful modality in cases of
      difficult visualization of the IUD; VCI-C visualization of the acoustic shadow of
      the IUD may provide an adjunctive approach.

PMID- 16632786
TI  - Adenomyosis:common and uncommon manifestations on sonography and magnetic
      resonance imaging.
AB  - OBJECTIVE: The purpose of this presentation is to show the imaging findings of
      the common and uncommon variants of adenomyosis as seen on sonography and
      magnetic resonance imaging (MRI). METHODS: A 3-year database search was performed
      to identify women who had pelvic sonography and pelvic MRI within a 6-month
      interval. Images of these cases were retrospectively reviewed. RESULTS: Eighty
      women were identified. Adenomyosis was diagnosed on MRI, which was used as the
      reference standard, in 45 of these women. The correct diagnosis was made on
      sonography in 73% of the cases. CONCLUSIONS: Awareness of the spectrum of imaging
      features of adenomyosis is important to use sonography effectively for diagnosing
      this entity and to help avoid misdiagnosis.

PMID- 16632787
TI  - Doppler ultrasonographic findings on hepatic arterial vasospasm early after liver
      transplantation.
AB  - OBJECTIVE: Hepatic arterial vasospasm has not been well recognized clinically as
      a post-liver transplant vascular complication because of the lack of sufficient
      data and diagnostic standards. The goal of this study was to provide new evidence
      and a diagnostic model for the clinical appreciation of hepatic arterial
      vasospasm and evaluate the role of ultrasonography in the diagnostic process.
      METHODS: Nine post-orthotopic liver transplant cases were retrospectively
      reviewed. Multiple clinical measurements were analyzed. Routine Doppler
      ultrasonography was performed within 24 hours, and additional ultrasonographic
      examinations were conducted as indicated. Each of the 9 patients was given a
      single 10 mg dose of nifedipine sublingually and monitored by ultrasonography
      when vasospasm was suspected on the basis of the Doppler ultrasonographic
      results. RESULTS: Doppler ultrasonography showed high-resistance hepatic arterial
      flow with absence of antegrade flow and even reversal of flow during diastole
      both extrahepatically and intrahepatically in all cases. Ten to 45 minutes after
      administration of the vasodilator, antegrade diastolic flow was observed along
      the course of the main hepatic artery and its intrahepatic branches with the
      resistive indices decreasing on average from 1.0 to 0.76. In addition, the peak
      systolic velocities increased from 57 cm/s before nifedipine administration to 77
      cm/s after administration. CONCLUSIONS: High-resistance hepatic arterial flow
      (resistive index = 1) early after liver transplantation is indicative of hepatic
      arterial vasospasm if it responds to vasodilators. Doppler ultrasonography is a
      useful tool for the diagnosis of this vascular complication.

PMID- 16632788
TI  - Sonographic findings of Zenker diverticula.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic findings of
      Zenker diverticula. METHODS: This study included 6 patients (age, 26-70 years;
      average, 55.3 years). Three cases were detected incidentally by thyroid
      sonograms, and 3 cases were transferred from other hospitals for aspiration of a
      thyroid nodule. All the sonograms and medical records were reviewed
      retrospectively. RESULTS: All 6 patients had no symptoms, and diverticula were
      incidentally detected by neck sonography. The masses were located on the
      posterolateral aspect of the left lobe in 5 patients and the right lobe in the
      remaining patient. All lesions were located in the upper and mid portions of the
      thyroid glands and showed echogenic foci similar to those of a microcalcification
      or an arc-shaped microcalcification. The sonographic findings of a Zenker
      diverticulum were seen as an isoechoic or a hypoechoic mass with internal or
      peripheral echogenic foci and a boundary hypoechoic zone at the posterior portion
      of the thyroid gland on sonography. All lesions appeared connected with the
      adjacent esophageal wall on sonography. In all cases, diagnoses were confirmed by
      esophagography. CONCLUSIONS: Zenker diverticula had several unique
      characteristics on sonography. We can, therefore, diagnose Zenker diverticula by
      careful thyroid sonography, avoiding unnecessary aspiration due to misdiagnosis
      of a Zenker diverticulum as a thyroid nodule.

PMID- 16632789
TI  - Giant mucocele of the appendix: clinical and imaging findings in 3 cases.
AB  - OBJECTIVE: Clinical and imaging (sonographic and computed tomographic [CT])
      findings in 3 cases of giant mucocele of the appendix are described. METHODS:
      Clinical records of 3 cases of giant mucocele of the appendix were reviewed. All
      patients had a basal B-mode sonographic examination and a contrast-enhanced
      sonographic examination using a second-generation low-mechanical index contrast
      medium. In all cases, a dual-phase spiral CT examination was carried out.
      RESULTS: In 2 cases, the abdominal masses were discovered in asymptomatic
      patients; 1 patient had vague abdominal discomfort. A pathologic diagnosis of
      benign cystoadenoma was found at pathologic examination in all cases, and
      malignant pseudomyxoma peritonei was disclosed in 1 patient 1 year later. Common
      sonographic findings were as follows: (1) a huge abdominal mass with a maximum
      diameter ranging between 20 and 25 cm; (2) a thin hyperechoic border without
      either solid vegetations or signs of infiltration of surrounding tissues; (3) a
      complex internal echo structure with anechoic lacunae interspersed between
      curvilinear, wavy bands of echogenic material (the so-called sonographic onion
      skin sign); and (4) avascularity of the masses shown on contrast-enhanced
      sonography with a low-mechanical index medium. At CT, a well-circumscribed
      cysticlike mass of low attenuation was displayed in all cases. There was lack of
      enhancement during a dual-phase examination in 2 cases; in the other, a small
      peripheral area of faint enhancement was appreciated. Only in the latter case
      could CT reliably assess the origin of the mass. CONCLUSIONS: It is suggested
      that a combination of sonographic (namely the onion skin sign) and CT findings
      may aid in the correct preoperative diagnosis of giant mucocele of the appendix.

PMID- 16632790
TI  - Characterization of solid breast masses: use of the sonographic breast imaging
      reporting and data system lexicon.
AB  - OBJECTIVE: The purpose of this study was to determine the reliability of
      sonographic American College of Radiology Breast Imaging Reporting And Data
      System (BI-RADS) classification in differentiating benign from malignant breast
      masses. METHODS: One hundred seventy-eight breast masses studied by sonography
      with a known diagnosis were reviewed. All lesions were classified according to
      the sonographic BI-RADS lexicon. Pathologic results were compared with
      sonographic features. Sensitivity, specificity, accuracy, and positive predictive
      value (PPV) and negative predictive value (NPV) for the sonographic BI-RADS
      lexicon were calculated. RESULTS: Twenty-six cases were assigned to class 3, 73
      to class 4, and 79 to class 5. Pathologic results revealed 105 malignant and 73
      benign lesions. The sonographic BI-RADS lexicon showed 71.3% accuracy, 98.1%
      sensitivity, 32.9% specificity, 67.8% PPV, and 92.3% NPV. The NPV for class 3 was
      92.3%. The PPVs for classes 4 and 5 were 46.6% and 87.3%. Typical signs of
      malignancy were irregular shape, antiparallel orientation, noncircumscribed
      margin, echogenic halo, and decreased sound transmission. Typical signs of
      benignity were oval shape and circumscribed margin. CONCLUSIONS: The sonographic
      BI-RADS lexicon is an important system for describing and classifying breast
      lesions.

PMID- 16632791
TI  - Unusual sonographic appearance of melanoma metastases in the breast.

PMID- 16632792
TI  - Sonographic demonstration of hyperechoic fibrin coating of rice bodies in
      trochanteric bursitis: the "fried rice" pattern.

PMID- 16632793
TI  - Degenerating cystic uterine fibroid mimics an ovarian cyst in a pregnant patient.

PMID- 16632794
TI  - Uterine carcinosarcoma arising from an endometrial polyp: assessment by 3
      dimensional power Doppler angiography and positron emission tomography/computed
      tomography.

PMID- 16632795
TI  - Sinus pericranii: color Doppler ultrasonographic findings.

PMID- 16632796
TI  - Detection of alimentary tract hemorrhage on contrast-enhanced ultrasonography.

PMID- 16632797
TI  - Absence of clustering of phosphatidylinositol-(4,5)-bisphosphate in fluid
      phosphatidylcholine.
AB  - Phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] plays a key role in the
      modulation of actin polymerization and vesicle trafficking. These processes seem
      to depend on the enrichment of PI(4,5)P(2) in plasma membrane domains. Here, we
      show that PI(4,5)P(2) does not form domains when in a fluid phosphatidylcholine
      matrix in the pH range of 4.8-8.4. This finding is at variance with the
      spontaneous segregation of PI(4,5)P(2) to domains as a mechanism for the
      compartmentalization of PI(4,5)P(2) in the plasma membrane. Water/bilayer
      partition of PI(4,5)P(2) is also shown to be dependent on the protonation state
      of the lipid.

PMID- 16632798
TI  - C-terminal interactions of apolipoprotein E4 respond to the postprandial state.
AB  - Increased triglyceride-rich lipoproteins (TGRLs) in the postprandial state are
      associated with atherosclerosis. We investigated whether the postprandial state
      induced structural changes at the apolipoprotein E4 (apoE4) C terminus, its
      principal lipid binding domain, using electron paramagnetic resonance (EPR)
      spectroscopy of a site-directed spin label attached to the cysteine of apoE4
      W264C. Spin coupling between labels located in the C termini was followed after
      mixing with preprandial and postprandial human plasma samples. Our results
      indicate that postprandial plasma triggers a reorganization of the protein such
      that the dipolar broadening is diminished, indicating a reduction in C-terminal
      interaction. The loss of spectral broadening was directly correlated with an
      increase in postprandial plasma triglycerides and was reduced with delipidated
      plasma. The spin-labeled apoE4 displayed a lipid preference of VLDL > LDL > HDL
      in the preprandial and postprandial states. The apoE4 shift to VLDL during the
      postprandial state was accompanied by a loss in spectral broadening of the
      protein. These findings suggest that apoE4 associated with LDL maintains self
      association via its C terminus and that this association is diminished in VLDL
      associated protein. Lipolyzed TGRL reflected a depletion of the C-terminal
      interaction of apoE4. Addition of palmitate to VLDL gave a similar response as
      lipolyzed TGRL, suggesting that lipolysis products play a major role in
      reorganizing apoE4 during the postprandial state.

PMID- 16632799
TI  - Analysis of intact phosphoinositides in biological samples.
AB  - It is now apparent that each of the known, naturally occurring
      polyphosphoinositides, the phosphatidylinositol monophosphates (PtdIns3P,
      PtdIns4P, PtdIns5P), phosphatidylinositol bisphosphates [PtdIns(3,4)P(2),
      PtdIns(3,5)P(2), PtdIns(4,5)P(2)], and phosphatidylinositol trisphosphate
      [PtdIns(3,4,5)P(3)], have distinct roles in regulating many cellular events,
      including intracellular signaling, migration, and vesicular trafficking.
      Traditional identification techniques require [(32)P]inorganic phosphate or
      [(3)H]inositol radiolabeling, acidified lipid extraction, deacylation, and ion
      exchange head group separation, which are time-consuming and not suitable for
      samples in which radiolabeling is impractical, thus greatly restricting the study
      of these lipids in many physiologically relevant systems. Thus, we have developed
      a novel, high-efficiency, buffered citrate extraction methodology to minimize
      acid-induced phosphoinositide degradation, together with a high-sensitivity
      liquid chromatography-mass spectrometry (LC-MS) protocol using an acetonitrile
      chloroform-methanol-water-ethylamine gradient with a microbore silica column that
      enables the identification and quantification of all phosphoinositides in a
      sample. The liquid chromatograph is sufficient to resolve PtdInsP(3) and
      PtdInsP(2) regioisomers; however, the PtdInsP regioisomers require a combination
      of LC and diagnostic fragmentation to MS(3). Data are presented using this
      approach for the analysis of phosphoinositides in human platelet and yeast
      samples.

PMID- 16632800
TI  - Cardiac function during intraperitoneal CO2 insufflation for aortic surgery: a
      transesophageal echocardiographic study.
AB  - The effect of laparoscopy on cardiac function is controversial. We hypothesized
      that cardiac dysfunction related to increased afterload could be predominant in
      patients undergoing elective abdominal aortic repair. To test this hypothesis, we
      conducted a transesophageal echocardiographic study in 15 patients during
      laparoscopic aortic surgery. We systematically assessed left ventricular (LV) and
      right ventricular (RV) functions. Measurements were obtained in the supine
      position without pneumoperitoneum and with an intraabdominal pressure of 14 mm
      Hg. Then, patients were turned to the right lateral position without
      pneumoperitoneum and intraabdominal pressure was increased to 7 mm Hg and to 14
      mm Hg. Pneumoperitoneum induced a 25% arterial blood pressure increase and a 38%
      increase in LV systolic wall stress. A 25% decrease in LV ejection fraction and
      an 18% decrease in LV stroke volume were observed, associated with an increase in
      LV end-systolic volume. LV diastolic function impairment was observed without
      change in LV end-diastolic volume. Respiratory alterations in superior vena cava
      diameter were never observed, suggesting that volume status remained optimal.
      Respiratory changes in RV stroke volume were increased according to
      intraabdominal pressure and body position, reflecting an increase in RV
      afterload. In conclusion, peritoneal CO2 insufflation in patients scheduled for
      laparoscopic aortic surgery could impair LV and RV systolic functions as a
      consequence of increased afterload.

PMID- 16632801
TI  - Acute hemodynamic collapse after induction of general anesthesia for emergent
      pulmonary embolectomy.
AB  - Patients undergoing pulmonary embolectomy often experience hemodynamic
      deterioration during induction of general anesthesia (GA). Therefore, we studied
      the incidence and possible risk factors for hemodynamic deterioration during GA
      induction. Fifty-two consecutive patients undergoing emergent pulmonary
      embolectomy at our institution were included. Hemodynamic collapse after GA
      induction was defined as hypotension refractory to vasopressor, inotrope, or
      fluid administration, requiring cardiopulmonary resuscitation followed by urgent
      institution of cardiopulmonary bypass (CPB). Demographic variables,
      comorbidities, specific location of thromboemboli, preoperative inotropic
      support, and anesthetic drugs used for GA induction were evaluated as possible
      risk factors. After GA induction, hemodynamic collapse occurred in 19% of
      patients (n = 10). However, the occurrence of hemodynamic instability was not
      predicted by any of the evaluated risk factors. In addition, the incidence of in
      hospital mortality did not differ between hemodynamically stable or unstable
      patients (10%; 4 of 42 versus 10%; 1 of 10 patients, respectively). In
      conclusion, hemodynamic deterioration after GA induction develops frequently
      during emergent pulmonary embolectomy. On the basis of our experience from this
      study and the unpredictable nature of hemodynamic deterioration, we suggest that
      patients undergoing pulmonary embolectomy should be prepared and draped before GA
      induction, and a cardiac surgical team should immediately be available for
      emergent institution of cardiopulmonary bypass.

PMID- 16632802
TI  - Measurement of patients' bivalirudin plasma levels by a thrombelastograph ecarin
      clotting time assay: a comparison to a standard activated clotting time.
AB  - Standard activated clotting time (ACT) tests have a poor correlation to
      bivalirudin levels, leading to uncertainty regarding adequate anticoagulation in
      percutaneous coronary intervention patients. We tested a Thrombelastograph (TEG)
      ecarin clotting time (ECT) assay for sensitivity to bivalirudin using blood from
      80 patients undergoing interventional cardiology procedures with bivalirudin
      anticoagulation. This was compared to a standard Hemochron ACT assay using
      diatomaceous earth. With the TEG assay, the direct thrombin activator, ecarin,
      was used to initiate coagulation and measured as the reaction time. Plasma
      samples were evaluated for bivalirudin by a chromogenic assay at an independent
      hematological laboratory. Linear regression of the standard ACT versus
      bivalirudin level gave an r = 0.306 whereas the TEG ECT gave a much higher r2 =
      0.746 (both P < 0.0001). The TEG ECT should prove more useful than the standard
      ACT for monitoring bivalirudin anticoagulation across the clinically therapeutic
      range.

PMID- 16632803
TI  - Small-dose recombinant activated factor VII (NovoSeven) in cardiac surgery.
AB  - Recombinant activated factor VII (rFVIIa) has been used at different doses in
      cardiac surgery patients. We tested the efficacy of small-dose rFVIIa in patients
      with intractable bleeding after cardiac surgery. The study group comprised 15
      cardiac surgery patients with intractable bleeding treated with small-dose (1.2
      mg) rFVIIa as a slow IV bolus at the end of complete step-by step transfusion
      protocol. Fifteen matched patients undergoing the same transfusion protocol in
      the pre-rFVIIa era represented the control group. Blood loss at the end of the
      transfusion protocol was a primary outcome. Median, 25th-75th 24-h blood loss
      percentiles were 1685 (1590-1770) mL versus 3170 (2700-3850) mL in study group
      and controls, respectively (P = 0.0004). Transfused red blood cells, fresh-frozen
      plasma, and platelets in the study group and controls were as follows: 7 (4-8) U
      versus 18 (12-21) U (P = 0.001); 7.5 (6-11) U versus 11 (9-15) U (P = 0.003); 0
      (0-4) U versus 9 (6-13) U (P = 0.001). In addition, significant improvements of
      prothrombin time (P = 0.015), international normalized ratio (P = 0.006),
      activated partial prothrombin time (P = 0.01), and platelet count (P = 0.003)
      were detected in the study group versus controls. Finally, patients receiving
      rFVIIa showed a reduced intensive care unit length of stay (chi2 = 15.9, P =
      0.0001) and had infrequent surgical re-exploration (chi2 = 16.2,P < 0.0001).
      Small-dose rFVIIa showed satisfactory results in cardiac patients with
      intractable bleeding. Further randomized studies are necessary to confirm our
      findings.

PMID- 16632804
TI  - The accuracy of the central landmark used for central venous catheterization of
      the internal jugular vein.
AB  - We simulated needle paths based on the central landmark used for central venous
      catheterization of the internal jugular vein. We obtained ultrasound images to
      quantify the landmark's accuracy (precision and bias) in 107 subjects placed in
      Trendelenburg position with their heads turned 30-35 degrees. We also determined
      the frequency of simulated carotid artery puncture. The simulated needle path
      missed the middle 80% of the lumen of the internal jugular vein in 34% of
      subjects (95% confidence interval [CI], 25% to 44%) and traversed the carotid
      artery in 26% of subjects (95% CI, 18% to 35%). Both events occurred in 20% of
      subjects (95% CI, 13%-29%). The landmark had a medial bias of 3.7 mm (95% CI, 2.7
      to 4.8); it was more often (77 of 104 subjects) medial to the center of the right
      internal jugular vein (P < 0.001). The landmark was more likely to miss the
      internal jugular vein (odds ratio, 3.11; P < 0.016) and intersect the carotid
      (odds ratio, 3.03; P < 0.024) in obese patients. The central landmark should not
      be expected to yield frequent success on first needle pass without risk of
      carotid puncture because of its imprecision and bias. The measured bias should be
      considered when the central landmark is used for central venous catheterization.

PMID- 16632805
TI  - The measurement of neurovegetative activity during anesthesia and surgery in
      swine: an evaluation of different techniques.
AB  - In this study we evaluated, in 10 sevoflurane-anesthetized pigs undergoing
      abdominal surgery, different techniques for measuring autonomic nervous system
      (ANS) activity: ANSiscope index, spectral analysis of heart-rate variability,
      hemodynamic variables, and plasma catecholamines and cortisol levels. Animals
      underwent a 120-min anesthesia during which unilateral ovariectomy was performed.
      Cardiovascular and respiratory responses were monitored. ANSiscope indices
      (ANSindex sympathetic, ANSindex parasympathetic and balANSindex) were used to
      monitor ANS activity. Spectral analysis was performed using an autoregressive
      model with a parametric method. The low frequency (LF) and high frequency (HF)
      components were used to interpret the power spectral density of short-term
      electrocardiograms (ECGs). The relationship LF/(LF+HF) reflects sympathetic
      activity, HF/(LF+HF) indicates parasympathetic activity, and the LF/HF ratio
      gives the predominance of the system. Plasma concentrations of adrenaline,
      noradrenaline, and cortisol were determined at different times. Correlation (P <
      0.01) was found between the balANSindex and adrenaline levels and between LF/HF
      ratio and plasma adrenaline concentrations. Moreover, a significant (P < 0.01)
      correlation was found between the balANSindex and LF/HF ratio. However, no
      correlation was seen between the registered ANSiscope indices and hemodynamic
      variables. The correlation seen in this study suggests that the balANSindex could
      be a useful tool to monitor ANS activity during anesthesia and surgery.

PMID- 16632806
TI  - Anesthetic preconditioning with sevoflurane does not protect the spinal cord
      after an ischemic-reperfusion injury in the rat.
AB  - Anesthetic preconditioning (APC) is a protective mechanism, whereby exposure to a
      volatile anesthetic renders a tissue resistant to a subsequent ischemic insult.
      We hypothesized that APC of the rat spinal cord with sevoflurane would reduce
      neurologic deficit after an ischemic-reperfusion injury. Rats were randomly
      assigned to 1 of 5 groups. The ischemic preconditioning (IPC) group (n = 14) had
      3 min of IPC, 30 min of reperfusion, and 12 min of ischemia. The chronic APC
      (cSEVO) group (n = 14) had 1 h of APC with 3.5% sevoflurane on each of 2 days
      before ischemia. The acute APC (aSEVO) group (n = 14) had 1 h of APC with 3.5%
      sevoflurane followed by a 1-h washout period before the induction of ischemia.
      The controls (n = 14) underwent no preconditioning before ischemia. IPC
      attenuated the ischemia-reperfusion injury, whereas aSEVO and cSEVO groups were
      no better than control animals. Histologic evaluation of the spinal cord showed
      severe neurologic damage in all groups except for the IPC group and sham-operated
      rats. APC with sevoflurane did not reduce neurologic injury in a rat model of
      spinal cord ischemia. Traditional ischemic preconditioning had a strong
      protective benefit on neurologic outcome.

PMID- 16632807
TI  - Inhibition of glycogen synthase kinase enhances isoflurane-induced protection
      against myocardial infarction during early reperfusion in vivo.
AB  - Inhibition of glycogen synthase kinase (GSK)-beta protects against ischemia
      reperfusion injury. Brief exposure to isoflurane before and during early
      reperfusion after coronary artery occlusion also protects against infarction.
      Whether GSK-beta mediates this action is unknown. We tested the hypothesis that
      GSK inhibition enhances isoflurane-induced postconditioning. Rabbits (n = 88; 6
      to 7 per group) subjected to a 30-min coronary occlusion followed by 3 h
      reperfusion received saline, isoflurane (0.5 or 1.0 minimum alveolar
      concentration [MAC]) administered for 3 min before and 2 min after reperfusion,
      the selective GSK inhibitor SB216763 (SB21; 0.2 or 0.6 mg/kg), or 0.5 MAC
      isoflurane plus 0.2 mg/kg SB21. Other groups of rabbits pretreated with
      phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin (0.6 mg/kg), 70-kDa
      ribosomal protein s6 kinase (p70s6K) inhibitor rapamycin (0.25 mg/kg), or
      mitochondrial permeability transition pore (mPTP) opener atractyloside (5 mg/kg)
      received 0.6 mg/kg SB21 or 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Additional
      groups received the mPTP inhibitor, cyclosporin A (5 mg/kg), plus 0.2 mg/kg SB21
      with or without atractyloside pretreatment. Isoflurane (1.0 but not 0.5 MAC) and
      SB21 (0.6 but not 0.2 mg/kg) reduced (P < 0.05) infarct size (21% +/- 5%, 44% +/-
      7%, 23% +/- 4%, and 46% +/- 2%, respectively, of left ventricular area at risk,
      mean+/- sd; triphenyltetrazolium staining) as compared with control (42% +/- 6%).
      Isoflurane (0.5 MAC) plus 0.2 mg/kg SB21 and cyclosporin A plus 0.2 mg/kg SB21
      produced similar degrees of protection (24% +/- 4% and 27% +/- 6%, respectively).
      Atractyloside but not wortmannin or rapamycin abolished protection produced by
      0.6 mg/kg SB21 and 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Thus, GSK inhibition
      enhances isoflurane-induced protection against infarction during early
      reperfusion via a mPTP-dependent mechanism.

PMID- 16632808
TI  - The influence of B-cell lymphoma 2 protein, an antiapoptotic regulator of
      mitochondrial permeability transition, on isoflurane-induced and ischemic
      postconditioning in rabbits.
AB  - Brief exposure to isoflurane or repetitive, transient ischemia during early
      reperfusion after prolonged coronary artery occlusion protects against myocardial
      infarction by inhibiting the mitochondrial permeability transition pore (mPTP).
      Inhibition of mPTP during delayed ischemic preconditioning occurred concomitant
      with enhanced expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2).
      We tested the hypothesis that Bcl-2 mediates myocardial protection by isoflurane
      or brief ischemic episodes during reperfusion in rabbits (n = 91) subjected to a
      30-min left anterior descending coronary artery occlusion followed by 3 h
      reperfusion. Rabbits received 0.9% saline, isoflurane (0.5 or 1.0 minimum
      alveolar concentration, MAC) administered for 3 min before and 2 min after
      reperfusion, 3 cycles of postconditioning ischemia (10 or 20 s each) during early
      reperfusion, 0.5 MAC isoflurane plus 3 cycles of postconditioning ischemia (10
      s), or the direct mPTP inhibitor cyclosporin A (CsA, 10 mg/kg) in the presence or
      absence of the selective Bcl-2 inhibitor HA14-1 (2 mg/kg, i.p.). Isoflurane (1.0,
      but not 0.5, MAC) and postconditioning ischemia (20 s but not 10 s) significantly
      (P < 0.05) reduced infarct size (mean +/- sd, 21% +/- 4%, 43% +/- 7%, 19% +/- 7%,
      and 39% +/- 11%, respectively, of left ventricular area at risk) as compared with
      control (44% +/- 4%). Isoflurane (0.5 MAC) plus 10 s postconditioning ischemia
      and CsA alone also exerted protection. HA14-1 alone did not affect infarct size
      nor block protection produced by CsA but abolished reductions in infarct size
      caused by 1.0 MAC isoflurane, 20 s postconditioning ischemia, and 0.5 MAC
      isoflurane plus 10 s postconditioning ischemia. The results suggest that Bcl-2
      mediates isoflurane-induced and ischemic postconditioning by indirectly
      modulating mPTP activity in vivo.

PMID- 16632809
TI  - 3D transesophageal echocardiography: systolic anterior motion with hypertrophic
      obstructive cardiomyopathy.

PMID- 16632810
TI  - A primary high-grade pleomorphic pericardial liposarcoma presenting as syncope
      and angina.

PMID- 16632811
TI  - The analgesic efficacy of acetaminophen, ketoprofen, or their combination for
      pediatric surgical patients having soft tissue or orthopedic procedures.
AB  - The combined use of acetaminophen and a nonsteroidal antiinflammatory drug has
      been shown to provide better postoperative analgesia than either drug alone in
      several adult studies. However, there are no pediatric studies analyzing similar
      effects when the currently recommended doses of acetaminophen are used. In a
      double-blind, placebo-controlled design we randomized 120 children, aged 1-9 yr,
      undergoing orthopedic or soft tissue surgery, into 3 groups to receive either
      acetaminophen 60 mg/kg rectally and 40 mg/kg orally, ketoprofen 2 mg/kg IV twice,
      or the combination of the active drugs. The first drug doses were given at
      anesthetic induction and the second doses 8 h thereafter. During anesthesia all
      children received sevoflurane and a continuous infusion of remifentanil.
      Postoperative pain was evaluated by the behavioral objective pain scale (0-9) for
      24 h. The rescue medication was morphine 0.05 mg/kg IV. The primary outcome
      variable was morphine consumption. For statistical analysis, analysis of
      variance, chi2 test and Kaplan-Meier survival analysis were used. Morphine
      requirement was less in the combination than in the acetaminophen group both in
      the postanesthesia care unit (2.5 +/- 1.7 versus 3.9 +/- 2.1 morphine doses) and
      during the 24-h postoperative follow-up (4.1 +/- 2.5 versus 5.9 +/- 2.9 morphine
      doses) (P < 0.05). No differences existed between the ketoprofen and the
      acetaminophen groups. The objective pain scale scores were lowest in the
      combination group both in the postanesthesia care unit and in the postoperative
      ward (P < 0.05). When children were divided based on their surgery, opioid
      requirement and pain scores were less in the combination than in the parent drug
      groups only after orthopedic surgery. The combination of acetaminophen 100 mg/kg
      and ketoprofen 4 mg/kg in a day provided better analgesia and lower pain scores
      after orthopedic, but not soft tissue, surgery in children.

PMID- 16632812
TI  - An evaluation of efficacy of balloon inflation on venous cannulation pain in
      children: a prospective, randomized, controlled study.
AB  - Venipuncture is the most common painful event for a hospitalized child. We
      evaluated the efficacy of balloon inflation for attenuating venipuncture pain in
      children. Seventy-five pediatric patients aged 6-12 yr, ASA physical status I-II,
      of either sex, undergoing elective surgery were included in this prospective and
      randomized study. Patients were randomly divided into 3 equal groups of 25 each;
      Group I (control), Group II (distraction) pressed a rubber ball, and Group III
      (balloon) inflated a balloon. A manual venous occlusion was applied on the
      forearm and venipuncture was performed with a 22-gauge venous cannula. Pain was
      self-reported by a pain face scale with a 10-cm visual analog scale (VAS) placed
      at its back, where 0 = "no pain" and 10 = "worst imaginable pain." VAS scores of
      1-3 were rated as mild, 4-6 as moderate, and >6 as severe. Median (interquartile
      range) VAS score in the balloon group was 1 (3), which was reduced as compared
      with 2 (2) and 4 (2) observed in the distraction and control groups, respectively
      (P < 0.000). Significant reduction in the incidence and severity of venipuncture
      pain was also observed in the balloon group compared with the other 2 groups (P <
      0.05).

PMID- 16632813
TI  - What postoperative outcomes matter to pediatric patients?
AB  - Children are often excluded from making decisions related to their medical
      treatment, and parents' proxy reports are often used. This approach fails to
      consider that parents and children may differ in their perception of the child's
      health. In this study, we assessed children's decision-making processes related
      to postoperative pain management. Forty-five children who underwent an anterior
      cruciate ligament repair or Nuss procedure for pectus excavatum repair were
      studied. A standard gamble technique was used to assess children's perceptions of
      the utility of a hypothetical treatment that would provide them with perfect pain
      control, with respect to different rates of risk for vomiting during the
      postoperative period. The maximum risk of vomiting that the overall study
      population was willing to accept to decrease the pain level to zero was 32% +/-
      24%. Girls were willing to take a significantly higher risk (41% +/- 24%)
      compared to boys (25% +/- 22%) (P = 0.02). Children who actually experienced
      vomiting before they were questioned were willing to take a higher risk (46% +/-
      26%) compared to those who did not (23% +/- 17%) (P = 0.035). Children can
      express opinions about preferred postoperative outcomes and provide useful input
      about their care. Girls, more than boys, seem to perceive vomiting as less
      important than improved pain control in the postoperative period.

PMID- 16632814
TI  - The prevention of emergence agitation with tropisetron or clonidine after
      sevoflurane anesthesia in small children undergoing adenoidectomy.
AB  - Postoperative agitation is a common problem after sevoflurane anesthesia in
      children. In the present study, we evaluated if tropisetron or clonidine could
      reduce the incidence of postoperative agitation after day case adenoidectomy in
      small children. We included 75 unpremedicated children aged 1-7 yr who were
      randomly assigned to receive either placebo, tropisetron (0.1 mg/kg) or clonidine
      (1.5 microg/kg) after anesthesia induction. Anesthesia was induced and maintained
      with sevoflurane. Patients also received alfentanil (20 microg/kg) and diclofenac
      (1 mg/kg). Postoperative pain was treated with IV oxycodone (0.05 mg/kg). Time to
      achieve discharge criteria was recorded. Modified pain/discomfort scale was used
      assess the postoperative behavior. The incidence of postoperative agitation was
      significantly less (32%, 8/25 patients) in the tropisetron group compared with
      placebo (62%, 16/26 patients), P < 0.05). Clonidine could not prevent agitation
      (incidence 54%, 13/24). No adverse effects were noted during the study. Discharge
      times were similar between the groups (between 80 and 99 min on average). In
      conclusion, tropisetron 0.1 mg/kg significantly reduced the incidence of
      postoperative agitation after sevoflurane anesthesia. Clonidine 1.5 microg/kg did
      not differ from placebo with respect to postoperative agitation.

PMID- 16632815
TI  - The use of oral granisetron versus intravenous ondansetron for antiemetic
      prophylaxis in patients undergoing laparoscopic surgery: the effect on emetic
      symptoms and quality of recovery.
AB  - Based on comparative studies in patients receiving emetogenic chemotherapy, it
      has been suggested that granisetron would be more effective than ondansetron for
      the prevention of postdischarge nausea and vomiting (PDNV). However, there have
      been no direct comparisons of these two popular 5-HT3 antagonists with respect to
      PDNV and quality of recovery. We designed this randomized, double-blind study to
      compare the antiemetic efficacy of oral granisetron (1 mg) to a standard IV dose
      of ondansetron (4 mg) when administered for antiemetic prophylaxis as part of a
      multimodal regimen in a laparoscopic surgical population. A total of 220 patients
      undergoing laparoscopic surgery with a standardized general anesthetic technique
      were enrolled in this prospective study at two major medical centers. Patients
      were randomly assigned to one of two prophylactic treatment groups: the control
      (ondansetron) group received an oral placebo 1 h before surgery and ondansetron,
      4 mg IV, at the end of the surgery, and the granisetron group received
      granisetron, 1 mg per os, 1 h before surgery, and normal saline, 2 mL IV, at the
      end of the surgery. The early recovery profiles, requirement for rescue
      antiemetics, incidence of PDNV, and the side effects were recorded over the 48 h
      study period. In addition, nausea scores were assessed using an 11-point verbal
      rating scale at specific intervals in the postoperative period. The quality of
      recovery and patient satisfaction scores were recorded at 48 h after surgery. The
      demographic characteristics were similar in the two prophylaxis treatment groups,
      as well as the recovery times to patient orientation, oral intake, and hospital
      discharge. The incidences of PDNV, requirements for rescue antiemetics, and
      quality of recovery did not differ between the two study groups. The antiemetic
      drug acquisition costs to achieve comparable patient satisfaction with
      ondansetron and granisetron were US 25.65 dollars and 47.05 dollars,
      respectively. Therefore, ondansetron (4 mg IV) was more cost-effective than
      granisetron (1 mg per os) for routine antiemetic prophylaxis as part of a
      multimodal regimen in patients undergoing either outpatient or inpatient
      laparoscopic surgery.

PMID- 16632816
TI  - Hypnosis reduces preoperative anxiety in adult patients.
AB  - In this study we examined the effect of hypnosis on preoperative anxiety.
      Subjects were randomized into 3 groups, a hypnosis group (n = 26) who received
      suggestions of well-being; an attention-control group (n = 26) who received
      attentive listening and support without any specific hypnotic suggestions and a
      "standard of care" control group (n = 24). Anxiety was measured pre- and
      postintervention as well as on entrance to the operating rooms. We found that
      patients in the hypnosis group were significantly less anxious postintervention
      as compared with patients in the attention-control group and the control group
      (31 +/- 8 versus 37 +/- 9 versus 41 +/- 11, analysis of variance, P = 0.008).
      Moreover, on entrance to the operating rooms, the hypnosis group reported a
      significant decrease of 56% in their anxiety level whereas the attention-control
      group reported an increase of 10% in anxiety and the control group reported an
      increase of 47% in their anxiety (P = 0.001). In conclusion, we found that
      hypnosis significantly alleviates preoperative anxiety. Future studies are
      indicated to examine the effects of preoperative hypnosis on postoperative
      outcomes.

PMID- 16632817
TI  - Contrasting roles of the N-methyl-D-aspartate receptor in the production of
      immobilization by conventional and aromatic anesthetics.
AB  - We hypothesized that N-methyl-d-aspartate (NMDA) receptors mediate some or all of
      the capacity of inhaled anesthetics to prevent movement in the face of noxious
      stimulation, and that this capacity to prevent movement correlates directly with
      the in vitro capacity of such anesthetics to block the NMDA receptor. To test
      this hypothesis, we measured the effect of IV infusion of the NMDA blockers
      dizocilpine (MK-801) and (R)-4-(3-phosphonopropyl) piperazine-2-carboxylic acid
      (CPP) to decrease the MAC (the minimum alveolar concentration of anesthetic that
      prevents movement in 50% of subjects given a noxious stimulation) of 8
      conventional anesthetics (cyclopropane, desflurane, enflurane, halothane,
      isoflurane, nitrous oxide, sevoflurane, and xenon) and 8 aromatic compounds
      (benzene, fluorobenzene, o-difluorobenzene, p-difluorobenzene, 1,2,4
      trifluorobenzene, 1,3,5-trifluorobenzene, pentafluorobenzene, and
      hexafluorobenzene) and, for comparison, etomidate. We postulated that MK-801 or
      CPP infusions would decrease MAC in inverse proportion to the in vitro capacity
      of these anesthetics to block the NMDA receptor. This notion proved correct for
      the aromatic inhaled anesthetics, but not for the conventional anesthetics. At
      the greatest infusion of MK-801 (32 microg x kg(-1) x min(-1)) the MACs of
      conventional anesthetics decreased by 59.4 +/- 3.4% (mean +/- sd) and at 8 microg
      x kg(-1) x min(-1) by 45.5 +/- 4.2%, a decrease not significantly different from
      a 51.4 +/- 19.0% decrease produced in the EC50 for etomidate, an anesthetic that
      acts solely by enhancing gamma-amino butyric acid (GABA) receptors. We conclude
      that some aromatic anesthetics may produce immobility in the face of noxious
      stimulation by blocking the action of glutamate on NMDA receptors but that
      conventional inhaled anesthetics do not.

PMID- 16632818
TI  - Differential modulation of human N-methyl-D-aspartate receptors by structurally
      diverse general anesthetics.
AB  - N-Methyl-d-aspartate (NMDA) receptors have a presumed role in excitatory synaptic
      transmission and nociceptive pathways. Although previous studies have found that
      inhaled anesthetics inhibit NMDA receptor-mediated currents at clinically
      relevant concentrations, the use of different experimental protocols, receptor
      subtypes, and/or tissue sources confounds quantitative comparisons of the NMDA
      receptor inhibitory potencies of inhaled anesthetics. In the present study, we
      sought to fill this void by defining, using the two-electrode voltage-clamp
      technique, the extent to which diverse clinical and aromatic inhaled anesthetics
      inhibit the NR1/NR2B subtype of the human NMDA receptor expressed in Xenopus
      laevis oocytes. At 1 minimum alveolar anesthetic concentration (MAC), anesthetic
      compounds reversibly inhibited NMDA receptor currents by 12 +/- 6% to 74 +/- 6%.
      These results demonstrate that equianesthetic concentrations of inhaled
      anesthetics can differ considerably in the extent to which they inhibit NMDA
      receptors. Such differences may be useful for defining the role that this
      receptor plays in producing the in vivo actions of general anesthetics.

PMID- 16632819
TI  - Do N-methyl-D-aspartate receptors mediate the capacity of inhaled anesthetics to
      suppress the temporal summation that contributes to minimum alveolar
      concentration?
AB  - Antagonism of N-methyl-d-aspartate (NMDA) receptors markedly decreases the
      minimum alveolar concentration (MAC) of inhaled anesthetics. To assess the
      importance of suppression of the temporal summation NMDA receptor component of
      MAC, we stimulated the tail of rats with trains of electrical pulses of varying
      interstimulus intervals (ISIs) and determined the inhaled anesthetic
      concentrations (crossover concentrations) that suppressed movement at different
      ISIs. The slopes of crossover concentrations versus ISIs provided a measure of
      temporal summation for each anesthetic. We studied five anesthetics that differ
      widely in their in vitro capacity to block NMDA receptors. To block NMDA receptor
      transmission and reveal the NMDA receptor component, the NMDA receptor
      antagonist, MK801, was separately added during each anesthetic. Halothane,
      isoflurane, and hexafluorobenzene did not appreciably suppress the NMDA receptor
      components of temporal summation, which contributed to 21% to 29% of MAC (P <
      0.05 for each). Xenon and o-difluorobenzene suppressed these components to 8% to
      0%, respectively, of MAC (neither significant), consistent with their greater
      NMDA receptor blocking action in vitro. NMDA receptor blockade may contribute to
      the MAC produced by inhaled anesthetics that potently inhibit NMDA receptors in
      vitro but not those that have a limited in vitro effect.

PMID- 16632820
TI  - The minimum alveolar anesthetic concentration of 2-, 3-, and 4-alcohols and
      ketones in rats: relevance to anesthetic mechanisms.
AB  - The Meyer-Overton hypothesis predicts that anesthetic potency correlates
      inversely with lipophilicity; e.g., MAC times the olive oil/gas partition
      coefficient equals a constant of approximately 1.82 +/- 0.56 atm (mean +/- sd)
      for conventional inhaled anesthetics. MAC is the minimum alveolar concentration
      of anesthetic required to eliminate movement in response to a noxious stimulus in
      50% of subjects. In contrast to conventional inhaled anesthetics, MAC times the
      olive oil/gas partition coefficient for normal alcohols from methanol through
      octanol equals a constant one tenth as large as that for conventional inhaled
      anesthetics. The alcohol (C-OH) group causes a great affinity of alcohols to
      water, and the C-OH may tether the alcohol at the hydrophobic-hydrophilic
      interface where anesthetics are thought to act. We hypothesized that the position
      of the C-OH group determined potency, perhaps by governing the maximum extent to
      which the acyl portion of the molecule might extend into a hydrophobic phase.
      Using the same reasoning, we added studies of ketones with similar numbers of
      carbon atoms between the C=O group and the terminal methyl group. The results for
      both alcohols and ketones showed the predicted correlation, but the correlation
      was no better than that with carbon chain length regardless of the placement of
      the oxygen. The oil/gas partition coefficient predicted potency as well as, or
      better than, either chain length or oxygen placement. Hydrophilicity, as
      indicated by the saline/gas partition coefficient, also seemed to influence
      potency.

PMID- 16632821
TI  - Bronchial mucus transport velocity in patients receiving propofol and
      remifentanil versus sevoflurane and remifentanil anesthesia.
AB  - Volatile anesthetics reduce ciliary beat frequency in vitro. It has been reported
      that impaired bronchial mucus transport velocity (BTV) is associated with
      significantly increased pulmonary complications. In this study, we sought to
      determine in vivo differences in BTV, comparing patients having total IV
      anesthesia (TIVA) with propofol and remifentanil to anesthesia with sevoflurane
      and remifentanil. Twenty-two patients scheduled for elective general surgery were
      randomized to one of two groups: TIVA (propofol/remifentanil) or SEVO
      (sevoflurane/remifentanil). Thirty minutes after tracheal intubation, BTV was
      assessed by fiberoptic observation of the movement of methylene blue dye applied
      to the dorsal surface of the right main bronchus. BTV was significantly reduced
      in the SEVO group compared with the TIVA group (mean, 1.5 +/- 0.7 [0-2.3] versus
      4.8 +/- 2.1 [2.3-8.8] mm/min; P < 0.0001). Anesthesia with sevoflurane may lead
      to significantly impaired bronchociliary clearance in comparison to TIVA. This
      could have implications for perioperative pulmonary complications, in particular
      in patients at risk for pulmonary complications.

PMID- 16632822
TI  - Isoflurane modulates genomic expression in rat amygdala.
AB  - General anesthesia, at a minimum, provides amnesia and unresponsiveness. Although
      anesthetics have many modulatory effects on neuronal ionophore protein complexes,
      it is not clear that the resulting electrophysiologic changes are the sole
      mechanisms of clinical anesthetic action. Cells respond to environmental changes
      in several ways, including alterations in DNA transcription leading to changes in
      the cell's proteins. We sought to expose the changes in global genomic
      expression, seeking potential targets involved in the processes of anesthetic
      induced amnesia, and persistent long-term side effects of general anesthesia,
      including nausea and postoperative cognitive decline. Using Affymetrix GeneChips,
      we surveyed changes in expression across the entire expressed genome of Sprague
      Dawley rat (n = 10 baseline, n = 6 isoflurane) basolateral amygdala 6 h after
      exposure to 15 min of 2% (1.4 MAC) isoflurane. Isoflurane administration was
      associated with altered expression in 269 unique genes possessing functional
      annotation. Affected genes were related to DNA transcription, protein synthesis,
      metabolism, signaling cascades, cytoskeletal structural proteins, and neural
      specific proteins, among others. Even brief exposure to isoflurane leads to
      widespread changes in the genetic control in the amygdala 6 h after exposure.
      Gene expression is a dynamic process that may explain some long-term effects of
      anesthesia and that has the potential to modulate some of those effects using
      specific molecular therapeutics.

PMID- 16632823
TI  - S(+)-ketamine attenuates increase in electroencephalograph activity and amplitude
      height of sensory-evoked potentials during rapid opioid detoxification.
AB  - Anesthesia-assisted opioid detoxification offers an opportunity for patients who
      have undergone unsuccessful conventional detoxifications. Little is known of
      excitatory effects taking place in the central nervous system during this
      procedure. Because acute withdrawal is accompanied by N-methyl-d-aspartic acid
      (NMDA)-receptor activation we tested whether the administration of the
      nonspecific N-methyl-d-aspartic acid antagonist S(+)-ketamine results in a
      reduction of hyperactivity in the central nervous system. Thirty-one patients
      with a long history of opioid abuse were acutely withdrawn with naltrexone during
      propofol/clonidine anesthesia and mechanical ventilation. Electroencephalogram
      (EEG) power spectra as well as median nerve-evoked somatosensory potentials
      (SSEP) were determined at the following times: evening before detoxification
      (control), steady-state propofol/clonidine-anesthesia, 30 min after naltrexone
      administration, and 5 min and 60 min after additional S(+)-ketamine (1.5 mg/kg).
      Compared to steady-state anesthesia, naltrexone induced a decrease by 270% in the
      low delta (0.5-3 Hz) and an increase by 110% in the fast beta (13-30 Hz) domain
      of the EEG with only minor changes in the theta-(3-7 Hz) and alpha-(7-13 Hz)
      band. Simultaneously, mean amplitude of the late N(100) peak of the SSEP
      increased from 3.3 muV to 10.5 muV. The changes could be attenuated by the
      additional administration of S(+)-ketamine, 5 min and 60 min after injection.
      Cardiovascular changes were not a reliable index for monitoring acute withdrawal
      symptoms and determining termination of rapid opioid detoxification. In this
      regard, EEG power spectra and SSEP were more consistent and clinically useful
      variables. S(+)-ketamine is a valuable adjunct in the anesthetic regimen, since
      it attenuates hyperactivity of the central nervous system during rapid opioid
      detoxification.

PMID- 16632824
TI  - Novel depots of buprenorphine prodrugs have a long-acting antinociceptive effect.
AB  - An analgesic with a prolonged duration may be desirable in patients with long
      lasting pain. In this study, we evaluated the antinociceptive effects and
      durations of action of three novel depots of buprenorphine esters buprenorphine
      propionate, enanthate, and decanoate given by IM injection, in rats. The
      pharmacokinetic profiles of buprenorphine in blood after IM injection of these
      depots were also evaluated. Antinociception was evaluated using the plantar test.
      Buprenorphine concentrations in blood were assayed using high-performance liquid
      chromatography. We found that the traditional form of buprenorphine HCl (in
      saline) produced a dose-related antinociceptive effect. A dose of 0.6 micromol/kg
      buprenorphine HCl (in saline) produced a significant antinociceptive effect
      lasting 5 h. The same dose of buprenorphine base, propionate, enanthate, and
      decanoate (in oil) also produced a significant antinociceptive effect with longer
      durations of action of 26, 28, 52, and 70 h, respectively. The pharmacokinetic
      studies demonstrated that all the buprenorphine esters were prodrugs of
      buprenorphine. We conclude that the novel depots of buprenorphine prodrugs:
      buprenorphine propionate, enanthate, and decanoate produced a long-acting
      antinociceptive effect after IM injection in rats.

PMID- 16632825
TI  - Naloxone does not increase the minimum alveolar anesthetic concentration of
      sevoflurane in mice.
AB  - Several previous studies concluded that opioid receptors do not mediate the
      capacity of inhaled anesthetics to produce immobility in the face of noxious
      stimulation because administration of naloxone (a nonspecific opioid receptor
      antagonist) does not increase the minimum alveolar anesthetic concentration (MAC)
      of inhaled anesthetic that produces immobility in 50% of subjects given a noxious
      stimulation. In contrast, a recent study found that 0.1 mg/kg naloxone given
      intraperitoneally increased sevoflurane MAC in mice by 18% (P < 0.01). We
      repeated the recent study with sevoflurane in the same strain of mice,
      administering nothing (control), 0.1 mg/kg, and 1.0 mg/kg of naloxone. Our study
      differed in that we also tested a parallel group given saline rather than
      naloxone. We were blinded to drug administration. MAC decreased 4.8% +/- 11.0%
      (mean+/- sd) and 2.4% +/- 12.5% with the first and second administrations of
      saline. Similarly, MAC decreased 4.7% +/- 7.1% and 5.5% +/- 10.0% with the
      administration of 0.1 mg/kg and 1.0 mg/kg of naloxone. We do not find that
      naloxone increases MAC. Opioid receptors do not underlie a portion of the
      capacity of inhaled anesthetics to produce immobility.

PMID- 16632826
TI  - Spectral entropy and bispectral index as measures of the electroencephalographic
      effects of propofol.
AB  - Recently, Datex-Ohmeda introduced the Entropy Moduletrade mark for measuring
      depth of anesthesia. Based on the Shannon entropy of the electroencephalogram,
      state entropy (SE) and response entropy (RE) are computed. We investigated the
      dose-response relationship of SE and RE during propofol anesthesia in comparison
      with the Bispectral Indextrade mark (BIS). Twenty patients were studied without
      surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000
      mg/h (451 +/- 77 microg x min(-1) x kg(-1)) via a large forearm vein. Propofol
      was infused until substantial burst suppression occurred (more than 50%) or mean
      arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped
      until recovery of BIS values up to 60 was reached. Subsequently, the constant
      propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and
      again decreased (infusion was stopped) within the BIS value range of 40-60. The
      coefficient of determination (R2) and the prediction probability (P(K)) were
      calculated to evaluate the performance of SE, RE, and BIS to predict changing
      propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 +/-
      0.08, 0.89 +/- 0.07, and 0.92 +/- 0.06, respectively, were similar. The
      calculated P(K) values, however, revealed a significant difference between SE and
      RE compared with BIS, with P(K) = 0.77 +/- 0.09, 0.76 +/- 0.10, and 0.84 +/-
      0.06, respectively. BIS seems to show slight advantages in predicting propofol
      effect-site concentrations compared with SE and RE, as measured by P(K) but not
      as measured by R2.

PMID- 16632827
TI  - Remote anesthetic monitoring using satellite telecommunications and the Internet.
AB  - Remote collaboration for anesthesia requires considerable sharing of physiologic
      data, audio, and images on a consistent data platform. A low-bandwidth connection
      between Ecuador and the United States supported effective joint management of
      operative plan, airway, intraoperative decisions, and recovery. Transmission with
      a 64-Kbps InMarSat satellite telephone (Thrane & Thrane, Denmark) connection from
      hospitals in Macas and Sucua, Ecuador, to Richmond, Virginia, included
      preoperative patient evaluations, video of endotracheal intubations,
      electrocardiogram waveforms, pulse oximetry measurements, arterial blood pressure
      readings, capnography readings, and auscultation of breath sounds.

PMID- 16632828
TI  - An insidious failure of an oxygen analyzer.
AB  - We present a case of oxygen analyzer malfunction diagnosed by the failure of the
      patient to adequately breathe oxygen as measured by end-tidal oxygen
      concentration. A warning icon, compliant with international standards, was not
      noticed at the time by those involved in the patient's care. The role of
      effective medical device user interface design is discussed.

PMID- 16632829
TI  - The impact of therapy on quality of life and mood in neuropathic pain: what is
      the effect of pain reduction?
AB  - Mood and quality of life (QOL) outcomes vary widely in neuropathic pain trials.
      This may be a result of variable analgesia and other treatment effects. We
      evaluated the relationship between pain reduction and mood/QOL in neuropathic
      pain. Pain, side effects, QOL, and mood from a trial of morphine, gabapentin, and
      a morphine-gabapentin combination were examined. Baseline QOL was impaired
      according to Short Form Health Survey (SF-36) scores. Baseline mood, according to
      Profile of Mood States scores, was comparable to that of a nondepressed
      population. Pain reduction with all three active trial treatments correlated with
      improved QOL. Pain reduction with morphine and with gabapentin correlated with
      improved mood. Pain reduction with a morphine-gabapentin combination correlated
      with improvement in only one of several domains of the Profile of Mood States.
      Severity of sedation, constipation, and dry mouth during any treatment did not
      correlate with mood/QOL changes. These results can be interpreted to imply that
      larger analgesic treatment effect sizes lead to more substantial improvements in
      QOL and/or mood. However, other beneficial or adverse treatment-related side
      effects may also affect mood/QOL. Therefore, future studies are needed to also
      evaluate the impact of treatment-related side effects on mood/QOL in analgesic
      trials.

PMID- 16632830
TI  - Laparoscopic versus open myomectomy: a double-blind study to evaluate
      postoperative pain.
AB  - The advantages of laparoscopic over open surgery have been documented in
      nonblinded settings. Our prospective, double-blind setting evaluated pain scores
      72 h after surgery by comparing patients who underwent laparoscopic myomectomy or
      with laparotomy. Forty women referred for conservative myomectomy were included
      in the study. After stratification (myoma size, number of myomas, and surgeon),
      patients were randomized to either laparoscopy (n = 19) or laparotomy (n = 21)
      and received a standardized anesthesia and patient-controlled analgesia for 24 h
      after surgery. Identical wound dressings were applied to blind the patient and
      the observer to the surgical approach. The postoperative pain scores were
      documented on a visual analog scale (VAS; 0 = no and 10 = unbearable pain) at 24,
      48, and 72 h after surgery. As the primary outcome variable, we calculated the
      mean overall VAS-score at these time points. P < 0.05 (t-test and analysis of
      covariance) was considered statistically significant. There were no differences
      in patient characteristics among the groups. The mean overall VAS score at 24,
      48, and 72 h was statistically significantly lower in the laparoscopic group
      compared with the laparotomy group (2.28 +/- 1.38 versus 4.03 +/- 1.63; P <
      0.01). Our data demonstrate, for the first time in a double-blind setting, that
      laparoscopic myomectomy reduces postoperative pain for 72 h after surgery
      compared with laparotomy.

PMID- 16632832
TI  - Predicting anesthesia times for diagnostic and interventional radiological
      procedures.
AB  - We studied anesthesia times for diagnostic and interventional radiology using
      anesthesia billing data and paper radiology logbooks. For computerized tomography
      and magnetic resonance imaging procedures, we tried to predict future anesthesia
      times by using historical anesthesia times classified by Current Procedural
      Terminology (CPT) codes. By this method, anesthesia times were estimated even
      less accurately than operating room cases. Computerized tomography and magnetic
      resonance imaging had many different CPT codes, most rare, and CPT codes
      reflected organs imaged, not scanning times. However, when, anesthesia times were
      estimated by expert judgment, face validity and accuracy were good. Lower and
      upper prediction bounds were also estimated from the expert estimates. For
      interventional radiology, predicting anesthesia times was challenging because few
      CPT codes accounted for most cases. Because interventional radiologists scheduled
      their elective cases into allocated time, the necessary goal was not to estimate
      the time to complete each case but rather the time to complete each day's entire
      series of elective cases including turnover times. We determined the time of day
      (e.g., 4 pm) up to when interventional radiology could schedule so that on 80% of
      days the anesthesia team finishes no later than a specified time (e.g., 6 pm).
      Both diagnostic and interventional radiology results were similarly less accurate
      when Version 9 of the International Classifications of Diseases' procedure codes
      was used instead of CPT.

PMID- 16632831
TI  - Dysregulation of cellular calcium homeostasis in chemotherapy-evoked painful
      peripheral neuropathy.
AB  - Paclitaxel and vincristine are chemotherapeutic drugs that often evoke a long
      lasting painful peripheral neuropathy. Using drugs that reduce intracellular or
      extracellular calcium ions (Ca2+), we investigated the hypothesis that impaired
      Ca2+ regulation contributes to the chemotherapy-evoked neuropathic pain syndrome.
      For comparison, we also tested rats with painful peripheral neuropathy caused by
      nerve trauma and to the anti-human immunodeficiency virus nucleoside analog 2',3'
      dideoxycytidine (ddC). Normal naive (without neuropathy), paclitaxel-treated, and
      vincristine-treated rats received the following intrathecal injections: TMB-8 (46
      nmol), Quin-2 (1.8 nmol), EGTA (0.1 micromol), EGTA-am (0.1 micromol), and their
      vehicle controls. Chronic constriction injury (CCI) rats were examined after TMB
      8 and Quin-2 injections, and ddC-treated rats were examined after receiving TMB
      8. Mechano-allodynia and mechano-hyperalgesia were evaluated after each
      injection. Drug effects on heat hyperalgesia were also tested in CCI rats. All
      four Ca2+-reducing drugs significantly inhibited mechano-allodynia and mechano
      hyperalgesia in the rats treated with paclitaxel, vincristine, or ddC, but no
      effects were seen in the CCI or naive rats. We conclude that a similar
      abnormality of cellular Ca2+ homeostasis contributes to the pain caused by
      paclitaxel, vincristine, and ddC, but not posttraumatic painful peripheral
      neuropathy.

PMID- 16632833
TI  - Peer review interrater concordance of scientific abstracts: a study of
      anesthesiology subspecialty and component societies.
AB  - Abstracts presented at anesthesiology subspeciality and component society
      meetings are chosen by peer review. We assessed this process by examining
      selection criteria and determining interrater concordance. For the societies
      studied, the level of reviewer agreement ranged from poor to moderate, i.e.,
      slightly better than by chance alone. We hypothesize that having clearer
      evaluation criteria, scoring systems with interval scales, and assessment based
      on quality can strengthen the peer review process.

PMID- 16632834
TI  - Selective recruitment maneuvers for lobar atelectasis: effects on lung function
      and central hemodynamics: an experimental study in pigs.
AB  - We investigated whether selective lung recruitment of a lobar collapse would
      improve oxygenation and lung volume as well as a general (global) lung
      recruitment maneuver, with fewer circulatory side effects. In 10 ventilated,
      anesthetized pigs, a bronchial blocker was inserted in the right lower lobe,
      which was selectively lavaged to create a dense lobar collapse. The pigs were
      randomized into two orders of lung recruitment maneuvers (40 cm H2O airway
      pressure for 30 s): either a selective lung recruitment maneuver (using the inner
      lumen of the bronchial blocker) followed by a general lung recruitment maneuver,
      or vice versa. Median end-expiratory lung volume and median Pao2 increased
      significantly by approximately 100 mL and 16 kPa, respectively, with no
      significant differences between the two recruitment methods. There were no
      circulatory changes during the selective lung recruitment maneuver, but during
      the general lung recruitment maneuver, mean arterial blood pressure decreased
      significantly by 36 (21, 41) mm Hg (median, 25th and 75th percentiles), cardiac
      output by 2.1 (1.6, 2.5) L/min and left ventricular end-diastolic area by 4.4
      (3.5, 4.5) cm2. In conclusion, a selective recruitment maneuver improved lung
      function similar to a general lung recruitment maneuver but without any
      circulatory side effects.

PMID- 16632835
TI  - The influence of tidal volume on the dynamic variables of fluid responsiveness in
      critically ill patients.
AB  - Respiratory-related variabilities in stroke volume and arterial pulse pressure
      (Delta%Pp) are proposed to predict fluid responsiveness. We investigated the
      influence of tidal volume (Vt) and adrenergic tone on these variables in
      mechanically ventilated patients. Cyclic changes in aortic velocity-time
      integrals (Delta%VTI(Ao), echocardiography) and Delta%Pp (catheter) were measured
      simultaneously before and after intravascular volume expansion, and Vt was
      randomly varied below and above its basal value. Intravascular volume expansion
      was performed by hydroxyethyl starch (100 mL, 60 s). Receiver operating
      characteristic curves were generated for Delta%VTI(Ao), Delta%Pp and left
      ventricle cross-sectional end-diastolic area (echocardiography), considering the
      change in stroke volume after intravascular volume expansion (> or =15%) as the
      response criterion. Covariance analysis was used to test the influence of Vt on
      Delta%VTI(Ao) and Delta%Pp. Twenty-one patients were prospectively included; 9
      patients (43%) were responders to intravascular volume expansion. Delta%VTI(Ao)
      and Delta%Pp were higher in responders compared with nonresponders. Predictive
      values of Delta%VTI(Ao) and Delta%Pp were similar (threshold: 20.4% and 10.0%,
      respectively) and higher than that of left ventricle cross-sectional end
      diastolic area at the appropriate level of Vt. Delta%Pp was slightly correlated
      with norepinephrine dosage. Delta%Pp increased with the increase in the level of
      Vt both before and after intravascular volume expansion, contrasting with an
      unexpected stability of Delta%VTI(Ao). In conclusion, Delta%VTI(Ao) and Delta%Pp
      are good predictors of intravascular fluid responsiveness but the divergent
      evolution of these two variables when Vt was increased needs further explanation.

PMID- 16632836
TI  - The synergistic effects of pentoxifylline on systemic and regional perfusion
      after hemorrhage and hypertonic resuscitation.
AB  - Small volumes of hypertonic saline solution ([HS] 7.5% NaCl) produce systemic and
      microcirculatory benefits in hemorrhaged animals. Pentoxifylline (PTX) has
      beneficial effects when administrated after hemorrhagic shock. We tested the
      hypothesis that the combination of HS and PTX in the initial treatment of
      hemorrhagic shock provides synergistic hemodynamic benefits. Twenty-four dogs
      were bled to a target arterial blood pressure of 40 mm Hg and randomized into 3
      groups: lactated Ringer's solution (33 mL/kg; n = 6); HS (7.5% NaCl 4 mL/kg; n =
      9); and HS+PTX (7.5% NaCl 4 mL/kg + PTX 15 mg/kg; n = 9). Systemic hemodynamics
      were measured by Swan-Ganz and arterial catheters. Gastric mucosal-arterial Pco2
      gradient (D(g-a)Pco2; gas tonometry), portal vein blood flow (ultrasonic
      flowprobe), and systemic and regional O2-derived variables were also evaluated.
      HS induced a partial increase in mean arterial blood pressure, cardiac output,
      and portal vein blood flow. In the HS+PTX group, we observed a significant, but
      transitory, increase in systemic oxygen delivery (180 +/- 17 versus 141 +/- 13
      mL/min) in comparison to HS alone. PTX infusion during hypertonic resuscitation
      promoted a significant reduction in D(g-a)Pco2 (41.8 +/- 4.8 to 25.7 +/- 3.9 mm
      Hg) when compared with isolated HS infusion (48.2 +/- 6.4 to 39.4 +/- 5.5 mm Hg).
      We conclude that PTX as an adjunct drug during hypertonic resuscitation improves
      cardiovascular performance and gastric mucosal oxygenation.

PMID- 16632837
TI  - Alarm algorithms in critical care monitoring.
AB  - The alarms of medical devices are a matter of concern in critical and
      perioperative care. The frequent false alarms not only are a nuisance for
      patients and caregivers but can also compromise patient safety and effectiveness
      of care. The development of alarm systems has lagged behind the technological
      advances of medical devices over the last 20 years. From a clinical perspective,
      major improvements of alarm algorithms are urgently needed. We give an overview
      of the current clinical situation and the underlying problems and discuss
      different methods from statistics and computational science and their potential
      for clinical application.

PMID- 16632838
TI  - The use of somatosensory evoked potentials to determine the relationship between
      patient positioning and impending upper extremity nerve injury during spine
      surgery: a retrospective analysis.
AB  - Somatosensory evoked potential (SSEP) monitoring is used to prevent nerve damage
      in spine surgery and to detect changes in upper extremity nerve function. Upper
      extremity SSEP conduction changes may indicate impending nerve injury. We
      investigated the effect of operative positioning on upper extremity nerve
      function retrospectively in 1000 consecutive spine surgeries that used SSEP
      monitoring. The vast majority (92%) of upper extremity SSEP changes were reversed
      by modifying the arm position and were therefore classified as position-related.
      The incidence of position-related upper extremity SSEP changes was calculated and
      compared for five different surgical positions: supine arms out, supine arms
      tucked, lateral decubitus position, prone arms tucked, and the prone "superman"
      position. The overall incidence of position-related upper extremity SSEP changes
      was 6.1%. The lateral decubitus position (7.5%) and prone superman position
      (7.0%) had a significantly more frequent incidence of position-related upper
      extremity SSEP changes (P < 0.0001, Z-test for Poisson counts) compared with
      other positions (1.8%-3.2%). No patient with a reversible SSEP change developed a
      new postoperative deficit in the affected extremity. SSEP monitoring is of value
      in identifying and reversing impending upper extremity peripheral nerve injury.

PMID- 16632839
TI  - Precordial Doppler probe placement for optimal detection of venous air embolism
      during craniotomy.
AB  - Verification of appropriate precordial Doppler probe position over the anterior
      chest wall is crucial for early detection of venous air embolism. We studied
      responses to normal saline (NS) and carbon dioxide (CO2) test injections at
      various probe locations during elective craniotomy. All patients received four IV
      injections (10 mL of NS and 1 mL of CO2 via central and peripheral venous
      catheters). Doppler sounds were simultaneously recorded with two separate probes.
      In Group A, probes were placed in left and right parasternal positions. In Group
      B, the left probe was intentionally malpositioned as far laterally over the left
      precordium as was compatible with an audible signal. In Group A (n = 23), a left
      parasternal Doppler signal was easily obtainable in 23 of 23 patients, versus 18
      of 23 patients for the right parasternal probe (P < 0.05). In Group B (n = 17),
      central CO2 injection yielded a positive right parasternal response rate of 88%
      compared with 29% over the far left precordium (P < 0.015), where central NS
      injections yielded a 76% response rate (P < 0.015 versus central CO2 injection).
      Left parasternal placement is at least as sensitive to clinical venous air
      embolism events as right parasternal placement. Peripheral saline injection
      represents a viable alternative (83% response rate). Vigorous central injection
      of 10 mL of NS however, risks false positive verification of left lateral
      precordial probe placement.

PMID- 16632840
TI  - The combination of isoflurane and caspase 8 inhibition results in sustained
      neuroprotection in rats subject to focal cerebral ischemia.
AB  - Although isoflurane can reduce ischemic neuronal injury after short postischemic
      recovery intervals, data from our laboratory have demonstrated that this
      neuroprotection is not sustained and that delayed apoptotic neuronal death,
      mediated in part by activation of caspases, contributes to the gradual increase
      in the size of the infarction. We tested the hypothesis that the neuroprotective
      efficacy of isoflurane can be prolonged with the administration of z-IETD-fmk, a
      specific inhibitor of caspase 8. Fasted Wister rats were anesthetized with
      isoflurane and randomly allocated to awake-vehicle, isoflurane-vehicle, awake
      IETD, or isoflurane-IETD groups (n = 25 per group). Animals were subjected to 60
      min focal ischemia by filament occlusion of the middle cerebral artery (MCAO).
      Daily intracerebroventricular injections of z-IETD-fmk or vehicle were
      administered via an implanted cannula starting before ischemia and continuing
      until 14 days post-MCAO. Neurological assessment was performed 14 days after
      ischemia after which the volume of cerebral infarction and number of intact
      neurons in the peri-infarct cortex were determined. Total infarction volume was
      less in the isoflurane-IETD group than in awake-vehicle, isoflurane-vehicle, and
      awake-IETD groups. Infarction volume was also less in the awake-IETD group versus
      the awake-vehicle group. The number of intact neurons within the peri-infarct
      cortex was significantly less in the awake-vehicle group in comparison with the
      other three experimental groups. The isoflurane-IETD group had better neurologic
      outcomes than both vehicle-treated groups at 14 days post-MCAO. These results
      suggest that a combination of isoflurane and a caspase 8 inhibitor can produce
      neuroprotection that is evident even after a recovery period of 14 days. This
      combination demonstrated greater efficacy than the administration of either
      isoflurane or z-IETD-fmk alone. These results are consistent with the premise
      that continuing apoptosis contributes to the enlargement of cerebral infarction
      during the recovery period and that its inhibition can provide sustained
      neuroprotection.

PMID- 16632841
TI  - Dexmedetomidine as rescue drug during awake craniotomy for cortical motor mapping
      and tumor resection.
AB  - Dexmedetomidine, approved for providing sedation in the critical care
      environment, is also used during awake craniotomies to facilitate procedures such
      as cortical mapping. Herein, we describe the use of dexmedetomidine as a rescue
      drug during awake craniotomy avoiding conversion to general anesthesia, thus
      allowing completion of cortical mapping.

PMID- 16632842
TI  - Spinal anesthesia using single injection small-dose bupivacaine versus continuous
      catheter injection techniques for surgical repair of hip fracture in elderly
      patients.
AB  - Aging and disease may make elderly patients particularly susceptible to
      hypotension during spinal anesthesia. We compared the hemodynamic effect of
      continuous spinal anesthesia (CSA) and small dose single injection spinal
      anesthesia (SA) regarding the incidence of hypotension. Seventy-four patients
      aged >75 yr undergoing surgical repair of hip fracture were randomized into 2
      groups of 37 patients each. Group CSA received a continuous spinal anesthetic
      with a titration of 2.5 mg boluses every 15 min of isobaric bupivacaine, while
      group SA received a single injection spinal anesthetic with 7.5 mg of isobaric
      bupivacaine. The overall variations in noninvasive automated arterial blood
      pressure were not statistically significantly different in the 2 groups at
      baseline and after CSA or SA (not significant). In the SA group, 68% of patients
      experienced at least one episode of hypotension (decrease in systolic arterial
      blood pressure greater than 20% of baseline value) versus 31% of patients in the
      CSA group (P = 0.005). In the SA group, 51% of patients experienced at least one
      episode of severe hypotension (decrease in systolic arterial blood pressure more
      than 30% of baseline value) versus 8% of patients in the CSA group (P < 0.0001).
      In the CSA group, 4.5 +/- 2 mg of ephedrine was injected versus 11 +/- 2 mg in
      the SA group (P = 0.005). In the CSA group, 5 mg (2.5-10) of anesthetic solution
      was required versus 7.5 mg in the SA group (P < 0.0001). We conclude that, in
      elderly patients undergoing hip fracture repair, CSA provides fewer episodes of
      hypotension and severe hypotension compared with a single intrathecal injection
      of 7.5 mg bupivacaine.

PMID- 16632843
TI  - Stimulation of the posterior cord predicts successful infraclavicular block.
AB  - Infraclavicular (IC) block is often performed by localizing one cord within the
      brachial plexus sheath and placing all the local anesthetic solution at that
      location. We hypothesized that posterior cord stimulation would be associated
      with a greater likelihood of IC block success. We enrolled 369 patients scheduled
      for surgery to the lower arm or hand in a prospective, nonrandomized
      observational trial. All underwent IC blocks using a standard technique, and the
      cord stimulated immediately before drug injection was recorded. Motor and sensory
      functioning were evaluated 15 min after injection. Compared with stimulation of
      either the lateral or medial cord, stimulation of the posterior cord was
      associated with rapid onset of motor block in significantly more nerves, as well
      as a decreased likelihood of block failure (motor and sensory block inadequate to
      perform surgery). Failure rates were 5.8% for posterior cord, 28.3% for lateral
      (P < 0.05), and 15.4% for medial (P < 0.05). The differences were highly
      significant when adjusted for multiple possible confounders, such as gender, body
      mass index, location of the incision, and level of training of the individual
      performing the block (P < 0.001, lateral versus posterior; P = 0.003, medial
      versus posterior). A low failure rate was also predicted by stimulation of more
      than one cord simultaneously (P < 0.05). We conclude that injection after
      locating the posterior cord or multiple cords predicts successful IC block.

PMID- 16632844
TI  - Unrecognized drug-drug interactions: a cause of intraoperative cardiac arrest?
AB  - Many physicians overlook, or are unaware of, most drug-drug interactions. In our
      patient, the local anesthetic used for an axillary block may have been the
      precipitating drug in a cascade of drug-drug interactions that resulted in a
      cardiac arrest. The combination of multiple preoperative drug-drug interactions
      prevented the return of a stable native cardiac rhythm for almost 24 h. The
      mechanisms of interactions of these frequently used drugs are described, and the
      reader is guided to sources that identify and simplify the understanding of
      potentially dangerous drug-drug interactions.

PMID- 16632845
TI  - A comparison of sister chromatid exchanges in lymphocytes of anesthesiologists to
      nonanesthesiologists in the same hospital.
AB  - An increased incidence of sister chromatid exchanges (SCEs) in peripheral
      lymphocytes of operating room personnel exposed to waste anesthetic gases has
      been reported. We investigated whether the increase of SCEs in anesthesiologists
      was reversible. Twenty-five anesthesiologists exposed to waste anesthetic gases
      such as sevoflurane and nitrous oxide were compared with nonexposed internists
      working in the same hospital. The concentrations of sevoflurane and nitrous oxide
      in the operating rooms were measured. The incidence of SCE was measured in
      lymphocytes cultures of anesthesiologists before and after a 2-mo leave from the
      operating room. These values of SCE were compared with those of nonexposed
      physicians. Occupational exposure to sevoflurane and nitrous oxide in the
      operating rooms were above the threshold values. There was a significant
      difference in SCE values of the anesthesiologists compared with the nonexposed
      physicians (11.9 +/- 4.4 versus 4.2 +/- 1.1, P < 0.001). After a 2-mo leave from
      the operating room, the SCE values of the anesthesiologists were significantly
      lower compared with those taken before the leave (4.8 +/- 1.8 and 11.9 +/- 4.4,
      respectively, P < 0.001). We conclude that the increase of SCE in
      anesthesiologists exposed to increased environmental concentrations of waste
      anesthetics gases, such as sevoflurane and nitrous oxide, are reversible if they
      work free from exposure for 2 mo.

PMID- 16632846
TI  - Tactile fade detection with hand or wrist stimulation using train-of-four, double
      burst stimulation, 50-hertz tetanus, 100-hertz tetanus, and acceleromyography.
AB  - Residual neuromuscular blockade can be evaluated using acceleromyography, tactile
      assessment of train-of-four (TOF), double-burst stimulation (DBS), 50-Hz tetanus,
      or 100-Hz tetanus. Nerve stimulation can be at the hand or the wrist. We compared
      all these tests at both sites of stimulation. Rocuronium was given to 32 patients
      under sevoflurane anesthesia. The mechanomyographic adductor pollicis TOF ratio
      was measured at one extremity. In the other, stimulation was at the hand or the
      wrist, by random allocation, and the acceleromyographic TOF ratio was measured.
      During recovery, a blinded observer estimated tactile fade. The TOF fade became
      undetectable when mechanomyographic TOF ratio was (mean +/- sd) 0.31 +/- 0.15.
      For DBS, this threshold was 0.76 +/- 0.11. For 50-Hz tetanus, it was 0.31 +/-
      0.15. For 100-Hz tetanus, it was 0.88 +/- 0.18, with a range of 0.14-1.00. These
      tactile responses were the same for hand and wrist stimulation. When
      acceleromyographic TOF ratio reached 1.0, the mechanomyographic TOF ratio was
      0.89 +/- 0.06. With stimulation in the hand, acceleromyographic TOF ratio >1.0
      was less frequent than at the wrist. To exclude residual paralysis, TOF, DBS, and
      50-Hz tetanus are inadequate, 100-Hz tetanus is unreliable, and acceleromyography
      performs best.

PMID- 16632847
TI  - Is it time to perform all thoracic epidural placements under fluoroscopy?

PMID- 16632848
TI  - Epidural steroid injections after epidurography may prevent otherwise devastating
      complications.

PMID- 16632849
TI  - Fluoroscopy and safety of spinal interventional procedures.

PMID- 16632850
TI  - Minimizing complications in epidural steroid injections.

PMID- 16632851
TI  - Comments on the case report of paraplegia after intracord injection.

PMID- 16632852
TI  - Preinduction check-up of the anesthesia machine.

PMID- 16632853
TI  - Vascular cut-down: is there a role for the anesthesiologist?

PMID- 16632854
TI  - Recommendations for postinduction hypotension: are they supported by the
      evidence?

PMID- 16632855
TI  - Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by
      remifentanil?

PMID- 16632856
TI  - Ventricular tachycardia in a patient with Brugada syndrome during general
      anesthesia combined with thoracic paravertebral block.

PMID- 16632857
TI  - Alternative route transfusion for transplantation surgery in patients lacking
      accessible veins.

PMID- 16632858
TI  - Desflurane's effect on QTc interval: electrophysiological mechanisms need to be
      explored.

PMID- 16632859
TI  - Positioning for intubation in morbidly obese patients.

PMID- 16632860
TI  - Anesthesia for craniotomy with intraoperative awakening: how to avoid respiratory
      depression and hypertension?

PMID- 16632861
TI  - Stimulating catheters in continuous popliteal block.

PMID- 16632862
TI  - More difficulty in removing an arrow epidural catheter.

PMID- 16632863
TI  - Accidental subdural injection of ropivacaine.

PMID- 16632864
TI  - New JCAHO pain standard bigger threat to patient safety than envisioned.

PMID- 16632865
TI  - Veno-arterial extracorporeal membrane oxygenation in acute respiratory distress
      syndrome caused by leptospire sepsis.

PMID- 16632866
TI  - Plasma levels of levobupivacaine after combined posterior lumbar plexus and
      sciatic nerve blocks.

PMID- 16632867
TI  - Carboxyl terminus of Plakophilin-1 recruits it to plasma membrane, whereas amino
      terminus recruits desmoplakin and promotes desmosome assembly.
AB  - Plakophilins are armadillo repeat-containing proteins, initially identified as
      desmosomal plaque proteins that have subsequently been shown to also localize to
      the nucleus. Loss of plakophilin-1 is the underlying cause of ectodermal
      dysplasia/skin fragility syndrome, and skin from these patients exhibits
      desmosomes that are reduced in size and number. Thus, it has been suggested that
      plakophilin-1 plays an important role in desmosome stability and/or assembly. In
      this study, we used a cell culture system (A431DE cells) that expresses all of
      the proteins necessary to assemble a desmosome, except plakophilin-1. Using this
      cell line, we sought to determine the role of plakophilin-1 in de novo desmosome
      assembly. When exogenous plakophilin-1 was expressed in these cells, desmosomes
      were assembled, as assessed by electron microscopy and immunofluorescence
      localization of desmoplakin, into punctate structures. Deletion mutagenesis
      experiments revealed that amino acids 686-726 in the carboxyl terminus of
      plakophilin-1 are required for its localization to the plasma membrane. In
      addition, we showed that amino acids 1-34 in the amino terminus were necessary
      for subsequent recruitment of desmoplakin to the membrane and desmosome assembly.

PMID- 16632868
TI  - Reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin
      dehydrogenase expression in A549 human lung adenocarcinoma cells.
AB  - Human lung adenocarcinoma cells, A549, possess the capacity of expressing both
      cyclooxygenase-2 (COX-2) and NAD+-linked 15-hydroxyprostaglandin dehydrogenase
      (15-PGDH). Resting cells express little COX-2 but significant levels of 15-PGDH.
      Interleukin (IL) 1beta, tumor necrosis factor-alpha (TNF-alpha) or phorbol ester
      [phorbol 12-myristate 13-acetate (PMA)] induced the expression of COX-2, as
      revealed by western blot analysis. Combination of PMA and IL-1beta or TNF-alpha
      induced synergistically the expression of COX-2. Interestingly, cytokines and
      cytokine plus PMA-induced expression of COX-2 were accompanied by a
      downregulation of 15-PGDH. This was evident from both the western blot analysis
      and activity assay of 15-PGDH. It appears that the higher the expression of COX-2
      was induced, the lower the expression of 15-PGDH was found. This was further
      supported by the observation that overexpression of COX-2 but not COX-1 by
      adenovirus-mediated approach led to a decrease in 15-PGDH expression, indicating
      the specificity of COX-2. Furthermore, downregulation of the IL-1beta-induced
      expression of COX-2 by silencing RNA (siRNA) approach resulted in an increase in
      the expression of 15-PGDH by COX-2-siRNA but not by COX-1-siRNA, indicating that
      it was indeed the expression of COX-2 attenuating the expression of 15-PGDH. The
      IL-1beta-induced reduction of the expression of 15-PGDH was shown not to be
      mediated by COX-2-derived products since the presence of COX-2 inhibitors did not
      block the attenuation of the expression of 15-PGDH. Exogenous PGE2 also did not
      induce the reduction of the expression of 15-PGDH. However, overexpression of 15
      PGDH by transfection with recombinant plasmid encoding 15-PGDH or adenovirus
      mediated approach attenuated IL-1beta-induced expression of COX-2. On the
      contrary, downregulation of 15-PGDH expression by 15-PGDH-siRNA or 15-PGDH
      antisense approach resulted in an increase in IL-1beta-induced expression of COX
      2 but not that of COX-1. In fact, it was further observed that A549 clones
      expressing different degrees of 15-PGDH showed also different levels of COX-2
      expression after IL-1beta induction. The levels of IL-1beta-induced COX-2
      expression appeared to correlate inversely with those of 15-PGDH expression in
      the cells. These results support the contention that COX-2 and 15-PGDH are
      regulated reciprocally in A549 cells.

PMID- 16632869
TI  - The chemopreventive efficacy of inhaled oltipraz particulates in the B[a]P
      induced A/J mouse lung adenoma model.
AB  - This study explored the efficacy of oltipraz, a dithiolthione to prevent lung
      cancer by delivering it directly to the lung as inhaled particulates to obtain
      maximum efficacy with no toxicity. Two exposure regimens were used to compare the
      efficacies of early (Regimen-A) versus late (Regimen-B) intervention in
      prevention of lung tumorigenesis in A/J mice. Female A/J mice were exposed to 10,
      30 and 100 mg/m(3) exposure concentrations of oltipraz for 1.0 h a day for 5 days
      per week for 4 weeks in Regimen A. During the second and third week, mice
      received totally 6 mg of B[a]P via gavage and after 16 weeks, they were killed
      for tumor counting and pathology. In Regimen B, mice were treated first with
      B[a]P and, after a gap of 4 weeks, exposed to oltipraz at 100 mg/m(3) for 16
      additional weeks. At 22 weeks, animals were killed and necropsied for tumor
      scoring. The spontaneous tumors were few in untreated A/J mice (0.7 tumors/lung),
      whereas there was an average of 16.5 tumors per lung in the B[a]P group (20-fold
      induction). Evaluation of lung tumor multiplicity following exposure to oltipraz
      showed that oltipraz inhibited the tumor development in a dose-dependent manner
      (10-100 mg/m(3)) with inhibition ranging from 37 to 53% in Regimen A and 51% in
      Regimen B, when compared with the B[a]P group. Analysis of the tumor incidence
      showed that 81.5% of the animals had 10 or more tumors in the B[a]P group,
      whereas, in oltipraz exposure groups, there was a significant decrease in Regimen
      A (24-36%) and in Regimen B (42%). The data from this study show that oltipraz is
      an effective agent for lung cancer prevention, when it is delivered directly to
      the target tissue as aerosolized particulates.

PMID- 16632870
TI  - Effect of long-term tamoxifen exposure on genotoxic and epigenetic changes in rat
      liver: implications for tamoxifen-induced hepatocarcinogenesis.
AB  - Tamoxifen is a non-steroidal anti-estrogen used for the treatment of breast
      cancer and, more recently, as a chemopreventive agent in healthy women at high
      risk of developing breast cancer. On the other hand, tamoxifen is a potent
      hepatocarcinogen in rats, with both tumor-initiating and tumor-promoting
      properties. There is substantial evidence that hepatic tumors in rats are
      initiated as a result of formation of tamoxifen-DNA adducts; however, events
      subsequent to DNA adduct formation are not clear. Recently, it has been
      demonstrated that genotoxic carcinogens, in addition to exerting genotoxic
      effects, often cause epigenetic alterations. In the current study, we
      investigated whether or not the mechanism of tamoxifen-induced
      hepatocarcinogenesis includes both genotoxic and epigenetic components. Female
      Fisher 344 rats were fed a 420 p.p.m. tamoxifen diet for 6, 12, 18 or 24 weeks.
      Hepatic tamoxifen-DNA adduct levels, as assessed by high-performance liquid
      chromatography and electrospray tandem mass spectrometry, were 580 adducts/10(8)
      nt at 6 weeks, and increased to approximately 1700 adducts/10(8) nt by 18 weeks.
      Global liver DNA hypomethylation, as determined by an HpaII-based cytosine
      extension assay, was increased at all time points, with the maximum increase
      (approximately 200%) occurring at 6 weeks. Protein expressions of maintenance
      (DNMT1) DNA methyltransferase and de novo DNA methyltransferases DNMT3a and
      DNMT3b were decreased at all time points. Likewise, trimethylation of histone H4
      lysine 20 was significantly decreased at all time points. In contrast, non-target
      tissues (i.e. mammary gland, pancreas and spleen) did not show any changes in
      global DNA methylation or DNA methyltransferase activity. These data indicate the
      importance of genotoxic and epigenetic alterations in the etiology of tamoxifen
      induced hepatocarcinogenesis.

PMID- 16632871
TI  - Neuroprotective effects of neuroactive steroids in the spinal cord and peripheral
      nerves.

PMID- 16632872
TI  - Progesterone treatment of spinal cord injury: Effects on receptors,
      neurotrophins, and myelination.
AB  - In addition to its traditional role in reproduction, progesterone (PROG) has
      demonstrated neuroprotective and promyelinating effects in lesions of the
      peripheral and central nervous systems, including the spinal cord. The latter is
      a target of PROG, as nuclear receptors, as well as membrane receptors, are
      expressed by neurons and/or glial cells. When spinal cord injury (SCI) is
      produced at the thoracic level, several genes become sensitive to PROG in the
      region caudal to the lesion site. Although the cellular machinery implicated in
      PROG neuroprotection is only emerging, neurotrophins, their receptors, and
      signaling cascades might be part of the molecules involved in this process. In
      rats with SCI, a 3-d course of PROG treatment increased the mRNA of brain-derived
      neurotrophic factor (BDNF) and BDNF immunoreactivity in perikaryon and processes
      of motoneurons, whereas chromatolysis was strongly prevented. The increased
      expression of BDNF correlated with increased immunoreactivity for the BDNF
      receptor TrkB and for phosphorylated cAMP-responsive element binding in
      motoneurons. In the same SCI model, PROG restored myelination, according to
      measurements of myelin basic protein (MBP) and mRNA levels, and further increased
      the density of NG2+-positive oligodendrocyte progenitors. These cells might be
      involved in remyelination of the lesioned spinal cord. Interestingly,
      similarities in the regulation of molecular parameters and some cellular events
      attributed to PROG and BDNF (i.e., choline acetyltransferase, Na,K-ATPase, MBP,
      chromatolysis) suggest that BDNF and PROG might share intracellular pathways.
      Furthermore, PROG-induced BDNF might regulate, in a paracrine or autocrine
      fashion, the function of neurons and glial cells and prevent the generation of
      damage.

PMID- 16632874
TI  - Fast nongenomic effects of steroids on synaptic transmission and role of
      endogenous neurosteroids in spinal pain pathways.
AB  - Steroids exert long-term modulatory effects on numerous physiological functions
      by acting at intracellular/nuclear receptors influencing gene transcription.
      Steroids and neurosteroids can also rapidly modulate membrane excitability and
      synaptic transmission by interacting with ion channels, that is, ionotropic
      neurotransmitter receptors or voltage-dependent Ca2+ or K+ channels. More
      recently, the cloning of a plasma membrane-located G protein-coupled receptor for
      progestins in various species has suggested that steroids/neurosteroids could
      also influence second-messenger pathways by directly interacting with specific
      membrane receptors. Here we review the experimental evidence implicating
      steroids/neurosteroids in the modulation of synaptic transmission and the
      evidence for a role of endogenously produced neurosteroids in such modulatory
      effects. We present some of our recent results concerning inhibitory synaptic
      transmission in lamina II of the spinal cord and show that endogenous 5alpha
      reduced neurosteroids are produced locally in lamina II and modulate synaptic
      gamma-aminobutyric acid A(GABAA) receptor function during development, as well as
      during inflammatory pain. The production of 5alpha-reduced neurosteroids is
      controlled by the endogenous activation of the peripheral benzodiazepine receptor
      (PBR), which initiates the first step of neurosteroidogenesis by stimulating the
      translocation of cholesterol across the inner mitochondrial membrane. Tonic
      neurosteroidogenesis observed in immature animals was decreased during postnatal
      development, resulting in an acceleration of GABAA receptor-mediated miniature
      inhibitory postsynaptic current (mIPSC) kinetics observed in the adult.
      Stimulation of the PBR resulted in a prolongation of GABAergic mIPSCs at all ages
      and was observed during inflammatory pain. Neurosteroidogenesis might play an
      important role in the control of nociception at least at the spinal cord level.

PMID- 16632873
TI  - Neurogenic pain and steroid synthesis in the spinal cord.
AB  - The spinal cord (SC) is a biosynthetic center for neurosteroids, including
      pregnenolone (PREG), progesterone (PROG), and 3alpha/5alpha
      tetrahydroprogesterone (3alpha/5alpha-THP). In particular, an active form of
      cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory
      networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the
      conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the
      biosynthesis of all classes of steroids. To determine whether
      neurosteroidogenesis might be involved in the pivotal role played by the DH in
      nociception, effects of neurogenic pain provoked by sciatic nerve ligature were
      investigated on P450scc expression, cellular distribution, and activity in the
      SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats
      than in controls. The nerve ligature also increased the density of
      P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation
      of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly
      synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats.
      Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations
      in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP
      biosynthesis might be involved in endogenous mechanisms triggered by neuropathic
      rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG
      can also generate PROG, which decreases sensitivity to pain and protects nerve
      cells against degeneration. Because apoptotic cell death has been demonstrated in
      the DH during neuropathic pain, activation of neurosteroidogenesis in spinal
      tissues might also be correlated to the neuroprotective role of steroids in the
      SC.

PMID- 16632875
TI  - Motoneuron injury and repair: New perspectives on gonadal steroids as
      neurotherapeutics.
AB  - In this review, we will summarize recent work from our laboratory on the role of
      gonadal steroids as neuroprotective agents in motoneuron viability following cell
      stress. Three motoneuron models will be discussed: developing axotomized hamster
      facial motoneurons (FMNs); adult axotomized mouse FMNs; and immortalized,
      cultured mouse spinal motoneurons subjected to heat shock. New work on two
      relevant motoneuron proteins, the survival of motor neuron protein, and neuritin
      or candidate plasticity-related gene 15, indicates differential steroid
      regulation of these two proteins after axotomy. The concept of gonadal steroids
      as cellular stress correction factors and the implications of this for acute
      neurological injury situations will be presented as well.

PMID- 16632876
TI  - Neuroactive steroids: A therapeutic approach to maintain peripheral nerve
      integrity during neurodegenerative events.
AB  - It is now well known that peripheral nerves are a target for the action of
      neuroactive steroids. This review summarizes observations obtained so far,
      indicating that through the interaction with classical and nonclassical steroid
      receptors, neuroactive steroids (e.g., progesterone, testosterone and their
      derivatives, estrogens, etc.) are able to influence several parameters of the
      peripheral nervous system, particularly its glial compartment (i.e., Schwann
      cells). Interestingly, some of these neuroactive steroids might be considered as
      promising neuroprotective agents. They are able to counteract neurodegenerative
      events of rat peripheral nerves occurring after experimental physical trauma,
      during the aging process, or in hereditary demyelinating diseases. On this basis,
      the hypothesis that neuroactive steroids might represent a new therapeutic
      strategy for peripheral neuropathy is proposed.

PMID- 16632877
TI  - Myelin disorders: Causes and perspectives of Charcot-Marie-Tooth neuropathy.
AB  - Charcot-Marie-Tooth (CMT) disease is a common hereditary neuropathy that causes
      progressive distally pronounced muscle weakness and can lead to life-long
      disability in patients. In most cases, the disorder has been associated with a
      partial duplication of human chromosome 17 (CMT1A), causing 1.5-fold
      overexpression of the peripheral myelin protein 22 kDa (PMP22). Increased PMP22
      gene dosage results in demyelination, secondary axonal loss, and neurogenic
      muscle atrophy. Experimental therapeutic approaches based on the role of
      progesterone and ascorbic acid in myelin formation recently have reached
      preclinical proof-of-principle trials in rodents. It was shown that progesterone
      receptor antagonists can reduce PMP22 overexpression and clinical severity in a
      CMT1A rat model. Furthermore, ascorbic acid treatment reduced premature death and
      demyelination in a CMT1A mouse model. Thus, basic research has opened up new
      vistas for the understanding and treatment of hereditary neuropathies.

PMID- 16632879
TI  - Cloning, characterization, and expression of a new cry2Ab gene from Bacillus
      thuringiensis strain 14-1.
AB  - Bacillus thuringiensis is the major source for transfer of genes to impart insect
      resistance in transgenic plants. Cry2A proteins of B. thuringiensis are promising
      candidates for management of resistance development in insects owing to their
      difference from the currently used Cry1A proteins, in structure and insecticidal
      mechanism. The cry2Ab gene was found to lack a functional promoter and, hence, is
      cryptic in nature. The cry2Ab7 gene was cloned from a new indigenous B.
      thuringiensis strain, 14-1. Nucleotide sequencing of the cry2Ab gene cloned from
      B. thuringiensis strain 14-1 revealed an open reading frame of 1902 bp. The
      deduced amino acid sequence of Cry2Ab of B. thuringiensis strain 14-1 showed a
      variation in three amino acid residues in comparison to the holotype sequence,
      Cry2Ab1. Expression of the newly cloned cry2Ab gene was studied in an
      acrystalliferous strain of B. thuringiensis (4Q7) by fusing the cry2Ab gene
      downstream of cry2Aa promoter and orf1 + orf2 sequences. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of a spore-crystal mixture obtained from
      transformants of B. thuringiensis strain 4Q7 showed production of Cry2Ab protein
      of about 65 kDa. Alkali solubilized Cry2Ab7 protein showed toxicity against
      Helicoverpa armigera neonates.

PMID- 16632878
TI  - GABA receptor-mediated effects in the peripheral nervous system: A cross
      interaction with neuroactive steroids.
AB  - Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the
      adult mammalian central nervous system (CNS), exerts its action via an
      interaction with specific receptors (e.g., GABAA and GABAB). These receptors are
      expressed not only in neurons but also on glial cells of the CNS, which might
      represent a target for the allosteric action of neuroactive steroids. Herein, we
      have demonstrated first that in the peripheral nervous system (PNS), the sciatic
      nerve and myelin-producing Schwann cells express both GABAA and GABAB receptors.
      Specific ligands, muscimol and baclofen, respectively, control Schwann-cell
      proliferation and expression of some specific myelin proteins (i.e., glycoprotein
      P0 and peripheral myelin protein 22 [PMP22]). Moreover, the progesterone (P)
      metabolite allopregnanolone, acting via the GABAA receptor, can influence PMP22
      synthesis. In addition, we demonstrate that P, dihydroprogesterone, and
      allopregnanolone influence the expression of GABAB subunits in Schwann cells. The
      results suggest, at least in the myelinating cells of the PNS, a cross
      interaction within the GABAergic receptor system, via GABAA and GABAB receptors
      and neuroactive steroids.

PMID- 16632880
TI  - Screening thermotolerant white-rot fungi for decolorization of wastewaters.
AB  - To select a thermotolerant fungal strain for decolorization of wastewaters,
      ligninolytic enzyme production (lignin peroxidase, manganese peroxidase [MnP],
      and laccase), decolorization, and removal of total phenol and chemical oxygen
      demand (COD) were detected. Thirty-eight fungal strains were studied for enzyme
      production at 35 and 43 degrees C on modified Kirk agar medium including 2,2'
      azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and MnCl2. Thirteen
      strains grew on manganese-containing agar and provided green color on ABTS
      containing agar plates under culture at 43 degrees C. Decolorization of
      wastewater from alcohol distillery (WAD) by these strains was compared under
      static culture at 43 degrees C, and Pycnoporus coccineus FPF 97091303 showed the
      highest potential. Thereafter, immobilized mycelia were compared with free
      mycelia for WAD decolorization under culture conditions of 43 degrees C and 100
      rpm. The immobilized mycelia on polyurethane foam enhanced the ligninolytic
      enzyme production as well as total phenol and color removal. At about the same
      COD removal, MnP and laccase produced by immobilized mycelia were 2 and 19 times
      higher than by free mycelia; the simultaneous total phenol and color removal were
      3.1 and 1.5 times higher than the latter. Moreover, decolorization of synthesis
      dye wastewater was carried out at 43 degrees C and 100 rpm. More than 80% of 300
      mg/L of reactive blue-5 was decolorized by the immobilized mycelia within 1 to 2
      d for four cycles.

PMID- 16632881
TI  - Ethanol-induced changes in glycolipids of Saccharomyces cerevisiae.
AB  - Total glycolipid content of Saccharomyces cerevisiae cells increased in ethanol
      treated yeast cells. Sialic acid and hexosamine contents of glycolipids from
      ethanol-treated cells decreased, whereas those of hexoses increased. Increased
      sialidase activity in the presence of ethanol may be responsible for the decrease
      in sialic acid content of glycolipids. The saccharide moieties of glycolipids of
      S. cerevisiae consisted of fucose, mannose, galactose, and glucose. Ethanol
      treatment of yeast cells caused an increase in glucose and a decrease in
      galactose content of glycolipids. The changes in glucose content can be related
      to changes in beta-glucosidase activity under alcohol stress. The content of
      cerebrosides, sulfatides, and monoglucosyldiglycerides was enhanced following
      ethanol treatment. An increase in cerebroside as well as in sulfatide content
      during alcohol stress might play an important role in stabilizing the membrane
      both physically and structurally. Such variations in glycolipid content and
      composition of S. cerevisiae cells may represent an adaptive response to ethanol
      stress.

PMID- 16632882
TI  - Kinetics and thermal stability of two peroxidase isozymes from Eupatorium
      odoratum.
AB  - The Eupatorium odoratum leaf peroxidase exists as at least seven distinct
      isozymes (three cationic, three anionic, and one neutral). These isozymes were
      identified and separated by preparative iso-electric focusing. Thermal stability,
      including the activation enthalpy (deltaH*), free energy of inactivation
      (deltaG*) and activation entropy (deltaS*), and kinetic studies of two isozymes,
      one having a pI of 5.0 (E5) and another one having a pI of 7.0 (E7) with mol mass
      of 43 and 50 kD, respectively, were studied in detail. Of the molecular weight of
      E5 and E7, 25 and 32% correspond to the carbohydrate content of the isozymes.
      Optimal pH was in the acidic range of 3.6-3.8 for E5 and 3.8 for E7 with the
      oxidation of ABTS. E7 and E5 showed activation energy for inactivation, 194.8 and
      145.4 kJ/mol, respectively. Both the isozymes showed distinct substrate
      specificity. The catalytic specificity constant for E5 and E7 were 112 x 105 and
      124 x 105/s.M, respectively, when 2,2'-azino-bis-(3-ethylbenz-thiazoline-6
      sulfonic acid) was used as the substrate. Maximum affinity (i.e., lowest Km
      value) to H2O2 was shown by E5 and E7 along with Pyrogallol and was 0.02 and
      0.05/s.M, respectively.

PMID- 16632883
TI  - Production of natural fruity aroma by Geotrichum candidum.
AB  - Based on its aromatic potential, Geotrichum candidum isolated from olive
      vegetation water was tested for the production of volatile compounds. When G.
      candidum was cultivated on media with glucose as the carbon source, flavor
      volatile compounds were produced and accumulated in the broth. Fruity flavoring
      compounds (pineapple-like) such as esters and alcohols were analyzed by gas
      chromatography coupled to mass spectrometry, including ethyl esters of acetic
      acid and butyric acid, methyl-3-butan-1-ol, and methyl-2-propan-1-ol. Their
      synthesis corresponded to the stationary growth phase of the strain. Production
      of the volatile compounds reached 9.5 g/L of 2-hexanoic acid ethyl ester and 1.6
      g/L of benzaldehyde as the main concentrated molecules. Ethyl alcohol seems to be
      an intermediate metabolite in this pathway.

PMID- 16632884
TI  - Transcription analysis of recombinant saccharomyces cerevisiae reveals novel
      responses to xylose.
AB  - Lignocellulosic biomass, rich in hexose and pentose sugars, is an attractive
      resource for commercially viable bioethanol production. Saccharomyces cerevisiae
      efficiently ferments hexoses but is naturally unable to utilize pentoses.
      Metabolic engineering of this yeast has resulted in strains capable of xylose
      utilization. However, even the best recombinant S. cerevisiae strains of today
      metabolize xylose with a low rate compared to glucose. This study compares the
      transcript profiles of an S. cerevisiae strain engineered to utilize xylose via
      the xylose reductase-xylitol dehydrogenase pathway in aerobic chemostat cultures
      with glucose or xylose as the main carbon source. Compared to the glucose
      culture, 125 genes were upregulated, whereas 100 genes were downregulated in the
      xylose culture. A number of genes encoding enzymes capable of nicotinamide
      adenine dinucleotide phosphate regeneration were upregulated in the xylose
      culture. Furthermore, xylose provoked increased activities of the pathways of
      acetyl-CoA synthesis and sterol biosynthesis. Notably, our results suggest that
      cells metabolizing xylose are not in a completely repressed or in a derepressed
      state either, indicating that xylose was recognized neither as a fermentable nor
      as a respirative carbon source. In addition, a considerable number of the changes
      observed in the gene expression between glucose and xylose samples were closely
      related to the starvation response.

PMID- 16632885
TI  - Carboxy-terminal extension effects on crystal formation and insecticidal
      properties of Colorado potato beetle-active Bacillus thuringiensis delta
      endotoxins.
AB  - Many Bacillus thuringiensis crystal proteins, particularly those active against
      lepidopteran insects, have carboxy-terminal extensions that mediate bipyramidal
      crystal formation. These crystals are only soluble at high (>10.0) pH in reducing
      conditions such as generally found in the lepidopteran midgut. Most of the
      Colorado potato beetle (CPB)-active toxins lack such an extension, yet some
      toxins with a carboxy-terminal extension have cryptic activity against this
      insect, revealed only after in vitro solubilization. Crystal formation,
      morphology, protein content, and activity against CPB were compared for two sets
      of proteins, the Cry1-hybrid SN19 and Cry3Aa, both with and without a carboxy
      terminal extension. Cry3Aa, with or without extension, formed flat square or
      rectangular crystals. SN19 (with extension) and its derivative without extension
      formed irregular inclusion bodies. All Cry3Aa and SN19 crystals and inclusion
      bodies were almost equally active before and after in vitro presolubilization and
      could be solubilized in diluted CPB midgut extract. In contrast, bipyramidal
      crystals of Cry1Ba were insoluble under these conditions. Our results suggest
      that bipyramidal crystal formation typical for proteins with a carboxy-terminal
      extension may preclude activity against CPB, but that interfering with this
      crystal formation can increase the activity.

PMID- 16632886
TI  - A novel method to monitor the expression of microRNAs.
AB  - The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18-25
      nucleotides) with important roles in the regulation of gene expression. Although
      a large number of miRNAs have been identified in a variety of eukaryotic systems,
      the function of the vast majority of these molecules remains unknown. To study
      the functions of miRNAs, it is crucial to determine their spatial and temporal
      expression patterns. Although there are some existing methods that can analyze
      the expression of miRNAs, it is not an easy task for routine gene-expression
      studies. In this study, we have established a simple method to detect the
      expression of mature miRNAs. Total RNA was polyadenylated by poly(A) polymerase,
      and then cDNA was synthesized by a specific reverse transcriptase (RT) primer and
      reverse transcriptase using the poly(A)-tailed total RNA as templates. The
      expression of several mature miRNAs was assayed by this method. The expression
      profile of two miRNAs, determined by the polymerase chain reaction (PCR) assay,
      was identical to that determined by Northern blotting. All these data show that
      the poly(A)-tailed RT-PCR is a convenient method to detect the expression of
      miRNAs.

PMID- 16632887
TI  - Cloning and expression analysis of SKn-type dehydrin gene from bean in response
      to heavy metals.
AB  - A heavy metal responsive gene PvSR3 (GenBank accession number U54703) encoding an
      acid dehydrin was isolated from a mercuric chloride-treated bean (Phaseolus
      vulgaris L.) leaf cDNA library by differential screening using cDNAs derived from
      treated and untreated plants. The PvSR3 cDNA is 981-bp long and has a 606-bp open
      reading frame with a 202-residue-deduced amino acid sequence. The PvSR3 sequence
      contains two conserved repeats of the characteristic lysine-rich K segment
      (EKKGIMDKIKEKLPG) preceded by an 8-serine residue stretch, whereas the Y segment
      (DEYGNP) conserved motif is absent. The deduced protein has a calculated
      molecular weight of 23 kDa and an isoelectric point of 5.2. Sequence similarity
      and comparative analysis showed that PvSR3 shares 70 and 73% similarity with the
      dehydrin of poplar and pepper, respectively. Southern hybridizations indicated
      that PvSR3 was a low copy-number gene. Northern blot analysis revealed that PvSR3
      mRNA was weakly detected in seedling leaves. However, the gene expression was
      strongly stimulated by heavy metals, such as mercury, cadmium, arsenic, and
      copper, whereas virus infection and salt had little effect on it. In contrast,
      PvSR3 was not responsive to drought or abscisic acid (ABA), and was downregulated
      by UV radiation. Furthermore, PvSR3 was upregulated by the exogenous signaling
      molecules, including salicylic acid (SA) and hydrogen peroxide (H2O2). It is
      suggested that PvSR3 is extremely related to heavy metal stress, and might play
      an important role in metal detoxification and resistance to the damage caused by
      heavy metals.

PMID- 16632888
TI  - Automation of MLST using third-generation liquid-handling technology.
AB  - The molecular characterization of bacterial pathogens of clinical significance is
      increasingly important. Methods, such as multilocus sequence typing (MLST), allow
      bacterial strains to be characterized during case clusters, for antibiotic
      resistant strains to be monitored, and for the impact of new vaccines to be
      assessed. Our laboratory performs MLST on Neisseria meningitidis, Streptococcus
      pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. We have developed
      high-throughput automated methods to allow MLST to be performed in a time scale
      useful in a clinical setting. Here we describe the automation of MLST on a third
      generation liquid-handling robot.

PMID- 16632890
TI  - Enzymatic biosensors.
AB  - The biosensor field has grown enormously since the first demonstration of the
      biosensor concept by Leland C. Clark, Jr. in 1962. Today's biosensor market is
      dominated by glucose biosensors, mass-produced enzyme electrodes for the rapid
      self-diagnosis of blood glucose levels by diabetes sufferers. Here we take a
      historical look at the inception, growth, and development of the enzyme biosensor
      field from a commercial viewpoint. The current status of the technology is
      evaluated and future trends in this dynamic and fast-moving field are also
      anticipated.

PMID- 16632889
TI  - Control of the G2/M transition.
AB  - The G2 checkpoint prevents cells from entering mitosis when DNA is damaged,
      providing an opportunity for repair and stopping the proliferation of damaged
      cells. Because the G2 checkpoint helps to maintain genomic stability, it is an
      important focus in understanding the molecular causes of cancer. Many different
      methods have been used to investigate the G2 checkpoint and uncover some of the
      underlying mechanisms. Because cell cycle controls are highly conserved, a
      remarkable synergy between the genetic power of model organisms and biochemical
      analyses is possible and has uncovered control mechanisms that operate in many
      diverse species, including humans. CDC2, the cyclin-dependent kinase that
      normally drives cells into mitosis, is the ultimate target of pathways that
      mediate rapid arrest in G2 in response to DNA damage. Additional pathways ensure
      that the arrest is stably maintained. When mammalian cells contain damaged DNA,
      the p53 tumor suppressor and the Rb family of transcriptional repressors work
      together to downregulate a large number of genes that encode proteins required
      for G2 and M. Elimination of these essential cell cycle proteins helps to keep
      the cells arrested in G2.

PMID- 16632891
TI  - Differential effects of dietary selenium (se) and folate on methyl metabolism in
      liver and colon of rats.
AB  - A previous study compared the effects of folate on methyl metabolism in colon and
      liver of rats fed a selenium-deficient diet (< 3 microg Se/kg) to those of rats
      fed a diet containing supranutritional Se (2 mg selenite/kg). The purpose of this
      study was to investigate the effects of folate and adequate Se (0.2 mg/kg) on
      methyl metabolism in colon and liver. Weanling, Fischer-344 rats (n = 8/diet)
      were fed diets containing 0 or 0.2 mg selenium (as selenite)/kg and 0 or 2 mg
      folic acid/kg in a 2 x 2 design. After 70 d, plasma homocysteine was increased (p
      < 0.0001) by folate deficiency; this increase was markedly attenuated (p <
      0.0001) in rats fed the selenium-deficient diet compared to those fed 0.2 mg
      Se/kg. The activity of hepatic glycine N-methyltransferase (GNMT), an enzyme
      involved in the regulation of tissue S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH), was increased by folate deficiency (p < 0.006) and
      decreased by selenium deprivation (p < 0.0003). Colon and liver SAH were highest
      (p < 0.006) in rats fed deficient folate and adequate selenium. Although folate
      deficiency decreased liver SAM (p < 0.001), it had no effect on colon SAM. Global
      DNA methylation was decreased (p<0.04) by selenium deficiency in colon but not
      liver; folate had no effect. Selenium deficiency did not affect DNA
      methyltransferase (Dnmt) activity in liver but tended to decrease (p < 0.06) the
      activity of the enzyme in the colon. Dietary folate did not affect liver or colon
      Dnmt. These results in rats fed adequate selenium are similar to previous results
      found in rats fed supranutritional selenium. This suggests that selenium
      deficiency appears to be a more important modifier of methyl metabolism than
      either adequate or supplemental selenium.

PMID- 16632892
TI  - Influence of chromium-enriched yeast on blood glucose and insulin variables,
      blood lipids, and markers of oxidative stress in subjects with type 2 diabetes
      mellitus.
AB  - The aim of this study was to determine the effect of chromium (Cr)- enriched
      yeast on blood glucose and insulin variables, blood lipids, and blood markers of
      oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0
      yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass
      index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast
      (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The
      most interesting results were obtained by comparison of the change in the placebo
      group to the change in the Cr group. The Cr group showed a significantly greater
      increase in serum Cr compared to the placebo group (p < 0.05). Supplementation
      with Cr-enriched yeast was associated with a significant decrease in fasting
      serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress
      glutathione peroxidase activity and levels of reduced glutathione were
      essentially unchanged in the Cr group after 12 wk, but decreased significantly in
      the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated
      protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c
      tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum
      insulin decreased in both groups, with a greater tendency in the Cr group (-16.5%
      vs -9.5%). These data suggest that supplementation of well-controlled type 2
      diabetics with Cr-enriched yeast is safe and can result in improvements in blood
      glucose variables and oxidative stress.

PMID- 16632893
TI  - Bhasmas: unique ayurvedic metallic-herbal preparations, chemical
      characterization.
AB  - Bhasmas are unique Ayurvedic metallic preparations with herbal juices/fruits,
      known in the Indian subcontinent since the seventh century BC and widely
      recommended for treatment of a variety of chronic ailments. Twenty bhasmas based
      on calcium, iron, zinc, mercury, silver, potassium, arsenic, copper, tin, and
      gemstones were analyzed for up to 18 elements by instrumental neutron activation
      analysis, including their C, H, N, and S contents. In addition to the major
      constituent element found at % level, several other essential elements such as
      Na, K, Ca, Mg, V, Mn, Fe, Cu, and Zn have also been found in microg/g amounts and
      ultratrace (ng/g) amounts of Au and Co. These seem to remain chelated with
      organic ligands derived from medicinal herbs. The bhasmas are biologically
      produced nanoparticles and are taken along with milk, butter, honey, or ghee (a
      preparation from milk); thus, this makes these elements easily assimilable,
      eliminating their harmful effects and enhancing their biocompatibility. Siddha
      Makaradhwaja, a mercury preparation is found to be stoichiometrically HgS without
      any traces of any other element. Similarly, Swet Parpati is stoichiometrically
      KNO3 but is found to have Mn, Cu, Zn, Na, P, and Cl as well. An attempt has been
      made to correlate the metallic contents with their medicinal importance. Na and
      K, the two electrolytic elements, seem to be well correlated, although K/Na
      varies in a wide range from 0.06 to 95, with specifically low values for Ca-, Fe
      , and Zn-based bhasmas. K/P also varies in a wide range from 0.23 to 12, although
      for most bhasmas (n = 12), it is 2.3 +/- 1.2. Further, Fe/Mn is linearly
      correlated (r = 0.96) with Fe in nine noniron bhasmas.

PMID- 16632894
TI  - Seasonal and physiological variations in serum chemistry and mineral
      concentrations in cattle.
AB  - The present study reports the seasonal and physiological variations of copper,
      zinc, magnesium, iron, sodium chlorine, potassium, calcium, phosphorus, urea,
      alkaline phosphatase (ALP), creatinine (CR), aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), cholesterol, albumin, globulin, lactate
      dehydrogenase (LDH), and total protein concentrations in cattle. Two groups of
      mated (n = 14) and nonmated (n = 10) healthy cows were selected for the study.
      Serum samples were collected at each of four periods: (1) early pregnancy (May),
      (2) midpregnancy (August), (3) late pregnancy (October), and (4) lactation
      (February). Physiological variations result in changes of cholesterol, calcium,
      LDH, and total protein concentrations. Phosphorus varies only with seasonal but
      not physiological changes, whereas ALP, copper, magnesium, and potassium
      concentrations change with physiological and seasonal conditions. The copper
      concentration is increased through the pregnancy. Neither the seasonal nor the
      physiologic variations affect zinc, iron, sodium, chlorine, calcium, urea,
      creatinine, albumin, and globulin values in both groups in all periods. Thus,
      these values can be used as reference for both mated and nonmated bovines. The
      measured total protein might not reflect its true value because of dehydration
      during the hot season. These observations suggest that seasonal and physiologic
      variations have to be taken into consideration for the correct interpretation of
      serum chemistry and elements status in cattle. Nutritional supplements are
      required for cattle during certain periods to avoid a decline of their
      performance, which would then represent consequent economic loses.

PMID- 16632895
TI  - Mercuric chloride inhibits the in vitro uptake of glutamate in GLAST- and GLT-1
      transfected mutant CHO-K1 cells.
AB  - Glutamate is removed mainly by astrocytes from the extracellular fluid via high
      affinity astroglial Na+ -dependent excitatory amino acid transporters,
      glutamate/aspartate transporter (GLAST), and glutamate transporter-1 (GLT-1).
      Mercuric chloride (HgCl2) is a highly toxic compound that inhibits glutamate
      uptake in astrocytes, resulting in excessive extracellular glutamate
      accumulation, leading to excitotoxicity and neuronal cell death. The mechanisms
      associated with the inhibitory effects of HgCl2 on glutamate uptake are unknown.
      This study examines the effects of HgCl2 on the transport of 3H-D-aspartate, a
      nonmetabolizable glutamate analog, using Chinese hamster ovary cells (CHO)
      transfected with two glutamate transporter subtypes, GLAST (EAAT1) and GLT-1
      (EAAT2), as a model system. Additionally, studies were undertaken to determine
      the effects of HgCl2 on mRNA and protein levels of these transporters. The
      results indicate that (1) HgCl2 leads to significant (p < 0.001) inhibition of
      glutamate uptake via both transporters, but is a more potent inhibitor of
      glutamate transport via GLAST and (2) the effect of HgCl2 on inhibition of
      glutamate uptake in transfected CHO cells is not associated with changes in
      transporter protein levels despite a significant decrease in mRNA expression;
      thus, (3) HgCl2 inhibition is most likely related to its direct binding to the
      functional thiol groups of the transporters and interference with their uptake
      function.

PMID- 16632896
TI  - Interactive effects of selenium and chromium on mammary tumor development and
      growth in MMTV-infected female mice and their relevance to human cancer.
AB  - Evidence for interactive effects of chromium and selenium on the appearance of
      mammary tumors was obtained by exposing female virgin C3H mice infected with the
      murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate]
      and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory
      effect of Se on tumor development in a dose-dependent manner, shortened the tumor
      latency period, and accelerated tumor growth rates. Exposure to Cr also altered
      the levels of Se in the liver and kidneys of the mice, indicating that Cr
      interacts with Se and affects its organ distribution. Chromium must be added to
      the list of Se-antagonistic elements that weaken or abolish the antitumorigenic
      effects of Se. These findings are relevant to human cancer as previous studies
      revealed the age-corrected mortalities from breast and other major forms of
      cancer in different countries to be inversely correlated with the dietary Se
      intakes, and directly correlated with the estimated intakes of Cr and of other Se
      antagonistic elements. The presence of these elements in foods must be taken into
      account when estimating the optimal dose of supplemental Se for cancer risk
      reduction.

PMID- 16632897
TI  - Effect of physical restraint on oxidative stress in mice fed a selenium and
      vitamin E deficient diet.
AB  - Physical restraint has been associated with increased oxidative damage to lipid,
      protein, and DNA. The purpose of this experiment was to determine whether
      physical restraint would further exacerbate oxidative stress in mice fed a
      selenium (Se) and vitamin E (VE) deficient diet. Three-week- old mice were fed a
      Torula yeast diet containing adequate or deficient Se and VE. Menhaden oil was
      added to the deficient diet to impose an additional oxidative stress. After 4 wk
      feeding, half the mice in each group were restrained for 5 d in well-ventilated
      conical tubes for 8 h daily. Mice fed the Se and VE deficient diets had increased
      liver thiobarbituric acid-reactive substance (TBARS) levels and decreased liver
      glutathione peroxidase (GPX1) activity and alpha-tocopherol levels. Plasma
      corticosterone levels were elevated in restrained mice fed the deficient diet
      compared to unrestrained mice fed the adequate diet. Restraint had no effect on
      liver TBARS or alpha-tocopherol levels. Liver GPX1 activity, however, was lower
      in restrained mice fed the adequate diet. In addition, liver superoxide dismutase
      (SOD) activity was lower in the restrained mice fed the adequate or deficient
      diet. Thus, under our conditions, Se and VE deficient diet, but not restraint,
      increased lipid peroxidation in mice. Restraint, however, decreased antioxidant
      protection in mice due to decreased activities of GPX1 and SOD enzymes.

PMID- 16632898
TI  - Rasch analysis of a new construct: functional caregiving for adult children with
      intellectual disabilities.
AB  - This research examined empirical evidence for a new construct, Functional
      Caregiving, which is a theory about mothers' caregiving of their adult children
      with intellectual disabilities. A sample of 108 biological mothers and primary
      caregivers rated survey items about their confidence to perform caregiving tasks.
      Rasch rating scale analysis found 61 items defined an empirical construct with
      three caregiving levels: Advocacy, Personal Caregiving, and Community. Results
      show item separation was 3.11 with high reliability, .91, and mother separation
      was 2.93 and reliability, .90. Both items and mothers showed adequate INFIT and
      OUTFIT values. Item invariance was confirmed between older and younger mothers,
      and principle components analysis of item residuals did not reveal any major
      dimensionality threats. Item decomposition analysis showed FC content theory to
      account for 58 percent of item calibration variance (R2 = .58, F = 42.3, p <
      .001). These results have important practical implications for health and social
      services, as well as family caregiving, interdisciplinary practices, and health
      policy development.

PMID- 16632899
TI  - Whose criterion standard is it anyway?
AB  - A criterion-referenced standard is an important element of most successful
      professional testing programs. A growing body of evidence suggests that judge
      decisions are influenced by characteristics related to the normative experience
      of the individual judge (e.g. gender, age, etc.). This investigation used two
      health-care related boards to explore the effects of judge characteristics on the
      standards established. Two judge panels (composed of 26 and 30 members
      respectively) were used in a simplified Objective Standard Setting exercise to
      define examination cutoff points. Multi-faceted Rasch analyses were employed to
      detect and explore differences in judgment making. Significant but not
      necessarily consistent differences were found between panel judges on several
      examined characteristics. Results suggest that criterion-referenced standards
      defined by judge panels are inexorably connected to their normative experiences
      and are therefore wholly sample dependent. While stratification of judge panels
      is clearly an important element in defining standards, if they are ever to
      achieve the goals of Glaser (1963) and Majer (1962) including meaningful
      independence, more must be done to investigate these and other concerns. The case
      for the predictive validity of criterion-referenced standards has not thusfar
      been made in any convincing fashion.

PMID- 16632900
TI  - Adjusted Rasch person-fit statistics.
AB  - Two frequently used parametric statistics of person-fit with the dichotomous
      Rasch model (RM) are adjusted and compared to each other and to their original
      counterparts in terms of power to detect aberrant response patterns in short
      tests (10, 20, and 30 items). Specifically, the cube root transformation of the
      mean square for the unweighted person-fit statistic, t, and the standardized
      likelihood-based person-fit statistic Z3 were adjusted by estimating the
      probability for correct item response through the use of symmetric functions in
      the dichotomous Rasch model. The results for simulated unidimensional Rasch data
      indicate that t and Z3 are consistently, yet not greatly, outperformed by their
      adjusted counterparts, denoted t* and Z3*, respectively. The four parametric
      statistics, t, Z3, t*, and Z3*, were also compared to a non-parametric statistic,
      HT, identified in recent research as outperforming numerous parametric and non
      parametric person-fit statistics. The results show that HT substantially
      outperforms t, Z3, t*, and Z3* in detecting aberrant response patterns for 20
      item and 30-item tests, but not for very short tests of 10 items. The detection
      power of t, Z3, t*, and Z3*, and HT at two specific levels of Type I error, .10
      and .05 (i.e., up to 10% and 5% false alarm rate, respectively), is also
      reported.

PMID- 16632901
TI  - From Rasch scores to regression.
AB  - Rasch models provide a framework for measurement and modelling latent variables.
      Having measured a latent variable in a population a comparison of groups will
      often be of interest. For this purpose the use of observed raw scores will often
      be inadequate because these lack interval scale properties. This paper compares
      two approaches to group comparison: linear regression models using estimated
      person locations as outcome variables and latent regression models based on the
      distribution of the score.

PMID- 16632902
TI  - The stability of marker characteristics across tests of the same subject and
      across subjects.
AB  - This research investigates the stability of marker characteristics within a very
      short period of time for both tests on the same subject as well as tests on
      different subjects. It reports on the scoring of the scripts of the whole cohort
      of students that took three high stakes tests in 2003 in a European country: a
      Language test consisting of a Literacy and a Literature paper and a History test.
      The many-facets Rasch model was used to study marker severity and marking
      consistency and it was found that some markers had more stable characteristics
      than others. Although the stability of marker characteristics was generally weak,
      it was non-negligible (correlation indices as indicators of stability ranged up
      to 0.707). This study, however, is not absolutely accurate due to the small
      sample sizes employed and it can be added that more research is needed to reach
      definite results.

PMID- 16632903
TI  - Development of a Money Mismanagement Measure and cross-validation due to
      suspected range restriction.
AB  - A measure of the tendency to mismanage money was developed in an evaluation of a
      representative payee program for individuals with serious mental illnesses. A
      conceptual model was composed to guide item development, and items were tested,
      revised, added, and rejected in three waves of data collection. Rasch analyses
      were used to examine measurement properties. The resulting Money Mismanagement
      Measure (M3) consisted of 28 items with a Rasch person reliability at .72.
      Restriction of range was likely responsible for the low Rasch reliability.
      Validity analyses supported the construct validity of the M3. Subsequently, a
      cross-validation study was conducted on an untreated sample not as susceptible to
      range restriction. The M3 produced a Rasch person reliability = .85 with good
      validity. The M3 fills a gap that can facilitate research in the understudied
      area of money mismanagement.

PMID- 16632904
TI  - The Mixed-Rasch Model: an example for analyzing the meaning of response latencies
      in a personality questionnaire.
AB  - The present study uses the Mixed-Rasch Model to analyze questionnaire data. It is
      hypothesized that more than one latent sub-population (classes) can be
      identified. It is also hypothesized that response latencies and social
      desirability can be used to describe and discriminate the latent classes. Using
      the software WinMira 2001, data from the Eysenck-Personality-Profiler-German
      version (EPP-D) was analyzed. A so-called non-scaleable and a scaleable group of
      subjects were identified which differed with regard to the use of one response
      category, I don't know. However, there was no difference between these groups
      with regard to response latencies and social desirability. Results will be
      discussed with regard to the EPP-D scoring scheme as suggested in the manual.

PMID- 16632905
TI  - Comparison of proteinase, lipase and alpha-glucosidase activities from the
      clinical isolates of Candida species.
AB  - Proteinase, lipase and alpha-glucosidase activity in 81 clinically isolated
      Candida strains grown in nutrient-restricted media were comparatively measured,
      and the correlation between inducible enzyme activity and fungal growth was
      analyzed. Enzyme activity was assayed by colorimetric methods. Extracellular
      proteinase activity was significantly higher in Candida albicans, followed by C.
      parapsilosis and C. tropicalis. Extracellular lipase activity was observed in all
      6 Candida spp. in the descending order of C. albicans, C. tropicalis and C.
      parapsilosis. Cell surface alpha-glucosidase activity was significantly higher in
      C. tropicalis, C. albicans, and C. parapsilosis, but was not detected in the
      other three species. A relatively strong correlation was observed between
      proteinase activity and fungal growth (correlation coefficient: 0.72); a mild
      correlation was observed between lipase activity and fungal growth (0.55); and a
      slight correlation was observed between alpha-glucosidase activity and fungal
      growth (0.32). There was no correlation among the strains in the activity levels
      of the three enzymes. These results suggest that pathogenic fungi produce larger
      amounts of inducible hydrolytic enzymes, and that proteinase is most likely to be
      related to fungal growth in nutrient-restricted conditions.

PMID- 16632906
TI  - Mutations of conserved glycine residues within the membrane-spanning domain of
      human immunodeficiency virus type 1 gp41 can inhibit membrane fusion and
      incorporation of Env onto virions.
AB  - The membrane-spanning domain (MSD) of HIV-1 envelope protein (Env) has an
      additional glycine residue within a well-conserved putative transmembrane helix
      helix interaction motif, GXXXG, and forms a G(690)G(691)XXG(694) sequence (G,
      glycine; X, any residues; the numbering indicates the position within the Env of
      an infectious molecular clone, HXB2). Different from vesicular stomatitis virus G
      (VSV-G), the glycine residues of the GXXXG motif of HIV-1 showed higher tolerance
      against mutations, and a simultaneous substitution of G690 and G694 with leucine
      residues only modestly decreased fusion activity and replication capacity of HIV
      1. When G691 was further substituted with alanine, phenylalanine or leucine
      residue while G690 and G694 were substituted with leucine residues, the
      efficiency of membrane fusion decreased, with the decrease greatest occurring
      with the leucine substitution, a less severe decrease with phenylalanine, and the
      least severe decrease with alanine. Substitution with leucine residue also
      decreased the incorporation of Env onto virions, and the mutant showed the most
      delayed replication profile. Thus the presence of the extra glycine residue,
      G691, may increase the tolerance of the other two glycine residues against
      mutations than VSV-G. The fact that a more severe defect was observed for the
      leucine residue than the phenylalanine residue suggested that the function of Env
      depended on the steric nature rather than on the simple volume of the side chain
      of the amino acid residue at position 691. Based on this result, we propose a
      hypothetical model of the association among MSDs of gp41, in which G(691) locates
      itself near the helix-helix interface.

PMID- 16632907
TI  - Molecular characterization and clinical evaluation of dengue outbreak in 2002 in
      Bangladesh.
AB  - During the febrile illness epidemic in Bangladesh in 2002, 58 people died out of
      the 6,132 affected. Two hundred hospitalized patients were analyzed clinically,
      serologically and virologically to determine the features of this dengue
      infection. Among the 10- to 70-year-old age group of the 200 clinically suspected
      dengue patients, 100 (50%) were confirmed as dengue cases by virus isolation and
      dengue IgM-capture ELISA. Of the 100 dengue-confirmed cases, the mean age was
      29.0 (+/-12.4). The possible dengue secondary infection rate determined by
      Flavivirus IgG-indirect ELISA was 78% in 2002. Eight dengue virus strains were
      isolated, representing the first dengue virus isolation in the country, and all
      of the strains were dengue virus type-3 (DEN-3). Sequence data for the envelope
      gene of the DEN-3 Bangladeshi isolates were used in a phylogenetic comparison
      with DEN-3 from other countries. A phylogenetic analysis revealed that all 8
      strains of DEN-3 were clustered within a well-supported independent sub-cluster
      of genotype II and were closely related to the Thai isolates from the 1990s.
      Therefore, it is likely that the currently circulating DEN-3 viruses entered
      Bangladesh from neighboring countries.

PMID- 16632908
TI  - Mutations within protein kinase R-binding domain of NS5A protein of hepatitis C
      virus (HCV) and specificity of HCV antibodies in pretreatment sera of HCV
      chronically infected patients and their effect on the result of treatment.
AB  - We analyzed protein kinase R (PKR)-binding domain sequences of hepatitis C virus
      (HCV) NS5A protein and the profile of HCV-specific antibodies from pretreatment
      sera of HCV-chronically infected patients. Results were compared with clinical
      data to verify their influence on the course and result of therapy. Of 9 patients
      enrolled in a 12-month treatment with pegylated interferon alpha (PEG-IFN-alpha)
      plus ribavirin (RBV), 6 patients responded to therapy, as assessed by the lack of
      HCV RNA in their sera, and 3 did not. Among 8 HCV-1b-infected patients, those who
      responded did not have significantly more mutations in the IFN sensitivity
      determining region (ISDR) compared to non-responders (P = 0.637). Similarly, in
      the remaining 26-amino acid region of the PKR-binding domain, behind ISDR, the
      number of mutations did not differ significantly between the two groups (P =
      0.796). A correlation was found between the presence of envelope 2 (E2)-specific
      antibodies and the result of treatment (P = 0.048). This pilot study indicates
      that mutations in the PKR-binding domain of HCV genotype 1b do not correlate with
      outcome of PEG-IFN-alpha/RBV therapy. However, the presence of E2-specific
      antibodies in the pretreatment sera of HCV-chronically infected individuals could
      serve as a prognostic marker predicting the result of treatment, before its
      initiation.

PMID- 16632909
TI  - Distribution of PrP(Sc) in cattle with bovine spongiform encephalopathy
      slaughtered at abattoirs in Japan.
AB  - Three 80- to 95-month-old Holstein dairy cattle infected naturally with the agent
      of bovine spongiform encephalopathy (BSE) and slaughtered at abattoirs in Japan
      were examined for the distribution of disease-specific and protease-resistant
      prion protein (PrP(Sc)) by immunohistochemistry (IHC) and Western blot (WB)
      analyses. The cattle showed no clinical signs or symptoms relevant to BSE but
      were screened as positive by enzyme-linked immunosorbent assay, a rapid test for
      BSE. This positive result was confirmed by IHC or WB in a specimen of the medulla
      oblongata. Histopathologically, these cattle showed no vacuolation in tissue
      sections from the central nervous system except for the medulla oblongata. Both
      IHC and WB analyses revealed PrP(Sc) accumulation in the brain, spinal cord,
      satellite and ganglionic cells of the dorsal root ganglia, and the myenteric
      plexus of the distal ileum. In addition, small amounts of PrP(Sc) were detected
      in the peripheral nerves of 2 cattle by WB. No PrP(Sc) was demonstrated by either
      method in the Peyer's patches of the distal ileum; lymphoid tissues including the
      palatine tonsils, lymph nodes, and spleen; or other tissues. The distribution of
      PrP(Sc) accumulation in the preclinical stage was different between naturally
      infected cattle and cattle inoculated experimentally with the BSE agent.

PMID- 16632910
TI  - Two cases of sucrose-fermenting Vibrio vulnificus infection in which 16S rDNA
      sequencing was useful for diagnosis.
AB  - Vibrio vulnificus is a Gram-negative bacterium which is associated with severe
      infections in humans. We experienced two cases of sucrose-fermenting V.
      vulnificus infection. The causative agents in both cases were unidentifiable by
      conventional identification systems because of their unique characteristics, and
      sequencing of 16S rDNA was found to be useful for diagnosis.

PMID- 16632911
TI  - Genetic and phenotypic characterization of Haemophilus influenzae type b isolated
      from children with meningitis and their family members in Vietnam.
AB  - To investigate Haemophilus influenzae type b (Hib) infection in Vietnamese
      children under the age of 5 years, cerebrospinal fluid (CSF) samples from
      patients with meningitis were screened for Hib, and isolates were subjected to
      evaluation of susceptibility to 12 antibiotics, biotyping, and genotyping with
      pulsed-field gel electrophoresis (PFGE). The major biotype was type II (68.3%),
      followed by type I (22.8%). Among 79 Hib isolates, 45 (57%) were beta-lactamase
      producing and ampicillin-resistant (44 and 1 isolates produced TEM-1- and ROB-1
      type beta-lactamases, respectively), and 34 isolates (43%) were beta-lactamase
      nonproducing and ampicillin-sensitive. No beta-lactamase-nonproducing and
      ampicillin-resistant isolates were found. The PFGE patterns of Hib isolates were
      highly divergent, but most could be classified into three clusters. We also
      investigated Hib colonization in household contacts of patients, and found that
      Hib isolates from the CSF of patients and from nasopharyngeal cavities of
      household contacts showed the same PFGE patterns. This observation suggested that
      household contacts of patients are a possible reservoir of Hib.

PMID- 16632912
TI  - Nalidixic acid resistance in Salmonella strains with decreased susceptibility to
      ciprofloxacin isolated from humans in Turkey.
AB  - The aim of this study was to evaluate the value of nalidixic acid resistance as
      an indicator of decreased susceptibility to ciprofloxacin (MIC = 0.125 - 1 mg/L)
      in Salmonella isolates from humans (n = 620) in Turkey. One isolate was found to
      be resistant, and the remaining isolates were susceptible to ciprofloxacin with
      the Clinical and Laboratory Standards Institute breakpoints; however, 75 isolates
      (12.1%) had decreased susceptibility. Resistance to nalidixic acid was observed
      in 76 (12.3%) isolates in the disk diffusion test. Seventy-four of these isolates
      had decreased susceptibility, one was fully resistant, and one isolate was
      susceptible to ciprofloxacin. One isolate with decreased susceptibility to
      ciprofloxacin was intermediate to nalidixic acid. Screening with 30-microg
      nalidixic acid disks had a sensitivity of 98.6% and a specificity of 99.8% for
      determination of decreased susceptibility to ciprofloxacin.

PMID- 16632913
TI  - The clinical picture of neonatal infection with Pantoea species.
AB  - Pantoea infections are uncommon in humans. Most reports have involved adults or
      children after thorn injuries. There are only a few reports of systemic
      infections with Pantoea. This is the first report of the clinical picture of
      systemic Pantoea spp. infection in neonates as observed during an outbreak in a
      neonatal intensive care unit caused by infected parenteral nutrition solutions.
      Even though detected early, the infections had a fulminant course, causing
      septicemic shock and respiratory failure. Pulmonary disease was prominent and
      presented mainly as pulmonary hemorrhage and adult respiratory distress syndrome.
      The organism was sensitive to most antibiotics used in neonatal intensive care
      units, but the clinical response to antibiotic therapy was poor. The fatality
      rate was very high: 7 out of 8 infected infants succumbed to the infection
      (87.5%).

PMID- 16632914
TI  - Analysis of a long-term discrepancy in drug-targeted genes in plasma HIV-1 RNA
      and PBMC HIV-1 DNA in the same patient.
AB  - Drug-resistance genotypes were investigated in a patient under treatment with
      anti-HIV drugs. Since the drug resistance-associated mutations in plasma HIV-1
      RNA and proviral DNA in peripheral blood mononuclear cells (PBMCs) were
      inconsistent, changes were followed over time, and the discrepancy was shown to
      persist for a long period. In plasma HIV-1 RNA, D67N, K70R, T215Y, and Y188L were
      present in the reverse transcriptase (RT) region, and two primary mutations, I84V
      and L90M, were noted in the protease (Pro) region. In contrast, in proviral DNA,
      no drug resistance-associated mutations were found in the RT region, and
      mutations such as L90L/M were only infrequently present in the Pro region. This
      situation persisted for more than 3 years. In addition, sequencing analysis of
      the V3 loop in the envelope gene showed that non-syncytium-inducing/macrophage
      tropic viruses contribute to acquisition of drug resistance. In this study, drug
      resistant viruses were produced primarily at macrophages, and drug-sensitive
      viruses were maintained in PBMCs as a reservoir.

PMID- 16632915
TI  - An unusual case of brain abscess by Gemella morbillorum.
AB  - A case of deep brain abscess by Gemella morbillorum is described. Due to high
      fever, lethargy, severe headache, and the risk of intraventricular rupture of the
      suppurative lesion, a CT-guided stereotactic aspiration of the abscess was
      successfully performed. The patient responded well to a 6-week course of
      meropenem, metronidazole, and fluconazole. Gemella spp. should not be considered
      as trivial commensals of the mucous membranes, but appear as emerging pathogens
      involved in endocarditis, septic shock, and necrotizing pneumonia, as well as in
      serious intracranial infections.

PMID- 16632916
TI  - Trichosporon asahii fungemia in a patient with non-hematological malignancy.
AB  - Trichosporon fungemia is usually seen in neutropenic patients with underlying
      hematological malignancies. In this report we describe a fatal case of
      Trichosporon asahii fungemia in a non-neutropenic patient with a non
      hematological malignancy. For 1 week the patient exhibited hematuria, weakness,
      easy fatigability and headaches. At admission she had anemia, renal failure and
      evidence of right hydronephrosis and bladder wall masses as detected by CT scan.
      She did not have a history of tobacco abuse, contact with urinary carcinogens or
      Schistosoma infestation; her clinical picture was suggestive of bladder cancer.
      After some investigations the patient underwent radical cystectomy and ileal
      conduit surgery because of transitional cell carcinoma in the urinary bladder.
      After an initial uneventful improvement postoperatively the patient deteriorated
      and died of septic shock despite all reanimation efforts and antibiotherapy
      including fluconazole. The blood culture obtained 4 days before the patient died
      revealed T. asahii, which was isolated on the day she died and found to be
      resistant to fluconazole and caspofungin. This report suggests that clinicians
      remain aware that T. asahii fungemia may develop in clinically deteriorated
      patients even if they do not have a hematological malignancy.

PMID- 16632917
TI  - A severe Salmonella enterica serotype Paratyphi B infection in a child related to
      a pet turtle, Trachemys scripta elegans.
AB  - Our report highlights a case of severe childhood salmonellosis related to a pet
      turtle, a red-eared slider (Trachemys scripta elegans). A 6-year-old girl had
      gastroenteritis complicated with sepsis caused by serotype Paratyphi B, which
      shared the same pulsed-field gel electrophoresis profiles with the organism
      isolated from a pet turtle. Based on our literature survey on childhood invasive
      salmonellosis acquired from reptiles, this case is the first documented reptile
      associated salmonellosis including sepsis caused by this serotype.

PMID- 16632918
TI  - A cluster of hepatitis E virus infection in Hokkaido, Japan.

PMID- 16632919
TI  - A diffuse outbreak of hepatitis E in Mie Prefecture, 2005.

PMID- 16632920
TI  - Rare group a rotavirus P[9]G3 isolated in Nara Prefecture, Japan.

PMID- 16632921
TI  - Characteristics of Norovirus outbreaks during a non-epidemic season.

PMID- 16632922
TI  - Isolation of influenza A/H3 and B viruses from an influenza patient: confirmation
      of co-infection by two influenza viruses.

PMID- 16632923
TI  - First isolation of influenza B virus in Kawasaki City, Kanagawa Prefecture, Japan
      in the 2005-2006 season.

PMID- 16632924
TI  - CMY-2 beta-lactamase-producing Salmonella enterica serovar infantis isolated from
      poultry in Japan.

PMID- 16632925
TI  - Maternal nutrition and adverse pregnancy outcomes: lessons from epidemiology.

PMID- 16632926
TI  - Metabolic disease: evolutionary, developmental and transgenerational influences.

PMID- 16632927
TI  - Nutrient effects upon embryogenesis: folate, vitamin A and iodine.

PMID- 16632928
TI  - Energy requirements during pregnancy and consequences of deviations from
      requirement on fetal outcome.

PMID- 16632929
TI  - Potential effects of nutrients on placental function and fetal growth.

PMID- 16632930
TI  - Essential fatty acids during pregnancy. Impact on mother and child.

PMID- 16632931
TI  - Dietary essential fatty acids in early postnatal life: long-term outcomes.

PMID- 16632932
TI  - Nutrient-induced maternal hyperinsulinemia and metabolic programming in the
      progeny.

PMID- 16632933
TI  - Maternal malnutrition and the risk of infection in later life.

PMID- 16632934
TI  - Size and body composition at birth and risk of type-2 diabetes.

PMID- 16632935
TI  - Cardiovascular disease in survivors of the Dutch famine.

PMID- 16632936
TI  - Relationship between maternal obesity and adverse pregnancy outcomes.

PMID- 16632937
TI  - Special problems of nutrition in the pregnancy of teenagers.

PMID- 16632938
TI  - Dietary Intervention during Pregnancy and Allergic Diseases in the Offspring.

PMID- 16632939
TI  - Future challenges of nutrition in pregnancy and lactation.

PMID- 16632940
TI  - The role of immune tolerance in allergy prevention.

PMID- 16632941
TI  - Prevention of food allergy during late infancy and early childhood.

PMID- 16632942
TI  - Celiac disease: effect of weaning on disease risk.

PMID- 16632943
TI  - Gut microbiota in infants between 6 and 24 months of age.

PMID- 16632944
TI  - Malabsorption of carbohydrates.

PMID- 16632945
TI  - Chronic nonspecific diarrhea of childhood.

PMID- 16632946
TI  - Development of motility.

PMID- 16632947
TI  - Motility and allergy.

PMID- 16632948
TI  - The role of dietary fiber in childhood and its applications in pediatric
      gastroenterology.

PMID- 16632949
TI  - Early influences on taste preferences.

PMID- 16632950
TI  - Junk food or 'junk eating'?

PMID- 16632951
TI  - Does nutrition during infancy and early childhood contribute to later obesity via
      metabolic imprinting of epigenetic gene regulatory mechanisms?

PMID- 16632952
TI  - Long-term effects of weaning habits: type-1 diabetes.

PMID- 16632953
TI  - What is known? Short-term and long-term effects of complementary feeding.

PMID- 16632954
TI  - Educational recommendations for processed foods for infant feeding.

PMID- 16632955
TI  - Recommendations for physicians and parents.

PMID- 16632956
TI  - Infant nutrition and primary prevention: current and future perspectives.

PMID- 16632957
TI  - Nutritional interventions in infancy and childhood for prevention of
      atherosclerosis and the metabolic syndrome.

PMID- 16632958
TI  - Childhood obesity: potential mechanisms for the development of an epidemic.

PMID- 16632959
TI  - Prenatal and postnatal development of obesity: primary prevention trials and
      observational studies.

PMID- 16632960
TI  - Childhood diabetes mellitus with emphasis on perinatal factors.

PMID- 16632961
TI  - The gut microbiota and potential health effects of intervention.

PMID- 16632962
TI  - The relationship of breastfeeding to the development of atopic disorders.

PMID- 16632963
TI  - Prevention of atopy and allergic disease: type of infant formula.

PMID- 16632964
TI  - Introduction of solid foods.

PMID- 16632965
TI  - Osteoporosis: is primary prevention possible?

PMID- 16632966
TI  - Nutrition and cancer prevention: targets, strategies, and the importance of early
      life interventions.

PMID- 16632967
TI  - Long-chain polyunsaturated fatty acids in early life: effects on multiple health
      outcomes. A critical review of current status, gaps and knowledge.

PMID- 16632968
TI  - Perinatal PUFA intake affects leptin and oral tolerance in neonatal rats and
      possibly immunoreactivity in intrauterine growth retardation in man.

PMID- 16632969
TI  - The crucial role of dietary n-6 polyunsaturated fatty acids in excessive adipose
      tissue development: relationship to childhood obesity.

PMID- 16632971
TI  - Primary prevention by nutrition intervention in infancy and childhood.
      Proceedings of the 57th Nestle Pediatric Nutrition Workshop. May 2005. San
      Francisco, California, USA.

PMID- 16632970
TI  - -Omics for prevention: gene, protein and metabolite profiling to better
      understand individual disposition to disease.

PMID- 16632972
TI  - [Colonoscopic diagnosis of hemoperitoneum].

PMID- 16632973
TI  - [Recent progress in diagnosis and treatment of rectal cancer].
AB  - Rectal cancer is an emerging health issue in Korea because its incidence is
      rapidly increasing with changes in life styles and diets. The optimal treatment
      of rectal cancer is based on multimodality. Among them, surgical treatment is the
      corner-stone. In the past, local recurrence rate has been reported as high as 30
      40%, but the concept of total mesorectal excision (TME) lowered the rate of local
      recurrence down to less than 10%. TME focuses on sharp pelvic dissection and
      complete removal of rectal cancer with surrounding mesorectum inside the rectal
      proper fascia. TME is now considered as a standard procedure for surgical
      treatment of mid and low rectal cancer. With the introduction of pelvic magnetic
      resonance imaging (MRI) for preoperative staging of rectal cancer, risk factors
      for local recurrence can be predicted before surgery to distinguish patients who
      are in high risk for recurrence that requires preoperative neoadjuvant
      chemoradiation therapy. Early rectal cancer was assessed by transrectal
      ultrasonography (TRUS) and endorectal MRI with coil. Transanal local excision can
      be applied with anal sphincter preservation safely. Neoadjuvant chemoradiation
      therapy was performed in patients with locally advanced rectal cancer, and this
      resulted in tumor size reductions and histopathologic downstaging effect. As far
      as the quality of life is concerned, sexual and voiding function are much
      improved by techniques preserving nerve. Many experts have dealt with challenging
      practical problems of managing rectal cancer from diagnosis to quality of life.
      This issue contains recent progresses in the diagnosis and treatment of rectal
      cancer which will serve as a comprehensive reference for those who manage rectal
      cancer in their medical practice.

PMID- 16632974
TI  - [Clinical significance of preoperative magnetic resonance imaging in staging of
      rectal cancer].
AB  - Rectal cancer carries poor prognosis because of metastasis and local recurrence.
      Local recurrence has a profound effect on morbidity and quality of life.
      Randomized trials have proven that neoadjuvant treatment can significantly reduce
      local recurrence rate in some selected cases of advanced rectal cancer.
      Therefore, preoperative staging of rectal cancer has an important impact on
      treatment plan. Two main factors in predicting the local recurrence are known as
      the circumferential resection margin (CRM) and the nodal status. Recently, high
      resolution magnetic resonance imaging (MRI) is regarded as a superior modality in
      the preoperative assessment of CRM with high accuracy and reproducibility.
      However, the results of imaging in predicting of nodal involvement are not
      satisfactory. In order to increase the accuracy of preoperative nodal staging,
      several efforts were done to evaluate lymph node by MRI or by pelvic MRI using
      lymph node-specific contrast agent (ultrasmall superparamagnetic iron oxide,
      USPIO). In this review, the role of MRI in preoperative evaluation of rectal
      cancer will be discussed.

PMID- 16632975
TI  - [Total mesorectal excision and preservation of autonomic nerves].
AB  - The procedure of total mesorectal excision (TME) becomes a gold standard for the
      treatment of rectal cancer. The reason is the marvelously low incidence of local
      recurrence after TME even without other adjuvant treatment, which has been
      reported by several independent groups. Although controversy still exists about
      the role of TME in upper rectal cancer, it is now widely accepted for cancers of
      the middle and lower third. There are number of histopathological evidences that
      cancer cells can spread distally several centimeters from the lower margin of
      cancer, and cancer bearing lymph nodes are found in the distal portion of the
      mesorectal tissues far from the cancer. Therefore, the distal clearance of
      mesorectum should be performed downwardly to the level of pelvic diaphragm
      (puborectalis) and the rectum is divided within a few centimeters from the pelvic
      floor musculature. TME defines an en-bloc procedure, along the plane between
      parietal and visceral pelvic fasciae. If the dissection plane is breached, the
      chance of visceral pelvic fascia tearing is raised and mesorectal tissue might
      reside in the pelvis. There are problems in auditing the procedure. As many
      surgeons agree, this procedure requires a learning curve. Theoretically, the
      autonomic nerves run between the visceral and parietal pelvic fasciae since the
      nerves must be preserved to make visceral fascial envelop. Any patient who become
      incontinent or impotent after the surgery should have received decorticating
      surgery other than TME. Thus, the high quality of TME should fulfill two clinical
      measurements: absence of impotence or incontinence and at least single digit, 5
      year, cumulative recurrence rate regardless of adjuvant therapy.

PMID- 16632976
TI  - [Sphincter-preserving surgery for rectal cancer].
AB  - Although optimal treatment of tumors at mid and distal rectum continues to be a
      matter of great debate to oncologic surgeons, a surgical goal of sphincter
      preservation should be considered in all patients with an intact sphincter. There
      are growing evidences and indications that sphincter-preserving procedure might
      be a valid alternative to conventional modality in tumors of the mid or lower
      rectum. Traditionally, an abdominoperineal resection with permanent colostomy
      would be the sole surgical option. Recently, a variety of sphincter-preserving
      procedures are performed in majority of distal rectal cancers with acceptable
      oncologic and optimal functional results. Several recent advances may further
      influence future treatment strategies and many issues are, at present, under
      evaluation. Here, some of the most relevant topics regarding current methods of
      sphincter-preserving procedures with their oncologic and functional results are
      discussed to establish the guideline of surgical treatment in rectal cancer.

PMID- 16632977
TI  - [Laparoscopic surgery for rectal cancer].
AB  - For more than a decade, laparoscopic surgery has been adopted as a treatment of
      colorectal cancer. With promising evidences from multi-center prospective
      randomized studies, laparoscopic approach is accepted as an alternative for the
      management of colon cancer. However, laparoscopic surgery is still technically
      demanding and has little evidence to convince most surgeons of its usefulness for
      rectal cancer. Laparoscopic surgery for malignant diseases must stress on
      oncologic safety as well as its functional excellence. Oncologic principles in
      surgery for rectal cancer are complete resection of the tumor with safe margins,
      en-bloc resection of regional lymph nodes and appropriate treatment for
      metastatic lesion. Despite the lack of results in prospective randomized
      comparative trials, many studies have been investigating whether laparoscopic
      resection for rectal cancer can follow these principles. In this review, we
      analyze early outcomes, long-term result of oncologic adequacy in laparoscopic
      surgery for rectal cancer, and discuss its potential advantages.

PMID- 16632978
TI  - [Chemotherapy in rectal cancer].
AB  - Until mid-1990s, fluorouracil was the only chemotherapeutic agent available for
      the treatment of colorectal cancer. The treatment of advanced colorectal cancer
      has evolved considerably over the last decade. Considerable improvements in
      survival as well as quality of life have been achieved with the application of
      oxaliplatin and irinotecan with fluoropyrimidine as a first and subsequent line
      therapy for colorectal cancer. Development of oral fluoropyrimidines as an
      alternative to intravenous administration provides an additional option for
      combination cytotoxic therapy, which is currently being assessed in phase III
      trials in advanced settings. The appearance of biologic agents in mid-2000s,
      namely cetuximab and bevacizumab, and their integration with conventional
      cytotoxic therapy for the treatment of colorectal cancer has additionally
      expanded the options for the treatment. Their dramatic success has led to further
      clinical studies of targeted therapy in colorectal cancer, making it one of the
      most promising areas of cancer research. Although considerable improvement was
      achieved by incorporating oxaliplatin in adjuvant chemotherapy for the treatment
      of colon cancer, there has been no phase III trial incorporating new agents in
      adjuvant setting for rectal cancer. However, many phase II trials on the efficacy
      of new agents in the setting of concurrent chemoradiation are in progress. Based
      on their results, randomized phase III clinical trials evaluating new agents in
      preoperative or postoperative setting will be carried out.

PMID- 16632979
TI  - [Radiation therapy for rectal cancer].
AB  - The current conventional treatment for locally advanced rectal cancer with stage
      II or III is surgery following or followed by chemoradiotherapy (CRT), which
      improved local control and overall survival when compared with surgery alone.
      Recently, a prospective randomized study with a large sample size and long-term
      follow-up reported that preoperative CRT resulted in improved local control and
      sphincter preservation, reduced toxicities, and comparative overall survival when
      compared with postoperative CRT. However, diagnostic imaging for accurate stage
      should be applied. In addition, chemotherapeutic regimen, schedule for radiation
      therapy, and timing of surgery should be also optimized in order to maximize the
      effect of preoperative CRT.

PMID- 16632980
TI  - [TNM staging, molecular staging and prognostic factors of rectal cancer].
AB  - Pathologic evaluation of the resected specimen is a critical component when
      managing the patients with rectal cancer, from initial diagnosis through
      definitive treatment. The best estimation of prognosis in rectal cancer is
      related to the anatomic extent of disease determined by pathology. Although a
      large number of staging system has been developed for rectal cancer over the
      years, use of TNM staging system of the AJCC (American Joint Committee on Cancer)
      and the UICC (International Union Against Cancer) are gaining popularity among
      the colorectal surgeons. Multiple genetic alterations are the prerequisite for
      carcinogenesis including rectal cancer. Although numerous molecular markers are
      investigated in relation to prognosis or response to therapy of rectal cancer,
      those molecular markers could not provide sufficient evidence for the
      incorporation of available prognostic biomarkers into clinical practice. In this
      article, the evolution of staging system of rectal cancer and its prognostic
      relevance are reviewed comprehensively.

PMID- 16632981
TI  - [The quality of life after rectal cancer surgery].
AB  - Surgery is a definite treatment for rectal cancer by resecting the tumor. Surgeon
      not only aims to cure the patient but aims to relieve distressing symptoms as
      well. Unfortunately, patients may suffer adverse consequences from such surgery.
      The operative dissection of the rectum may damage the pelvic autonomic nerves
      disturbing bladder and sexual function. The construction of a permanent colostomy
      following an abdominoperineal resection may be associated with one or more
      physical problems as well as clinically significant psychosocial problems as
      well. The advances in knowledge of tumor biology and the improvements of surgical
      techniques and devices result in an increasing number of sphincter saving
      procedures such as low anterior resection. Although avoiding permanent stoma is
      generally regarded as a favorable outcome measure, patients undergoing sphincter
      saving surgery may develop a number of unpleasant symptoms, typically fecal
      soiling and urgency, especially with low anastomosis. It is evident that the
      consequences of rectal surgery have an important bearing on quality of life.
      Although differences in definition exist, quality of life may be regarded as
      representing an individual's ability to carry out daily activities, as well as
      satisfaction with personal performance and with balance between disease control
      and adverse effects of treatment. In addition to traditional endpoints, such as
      survival and disease recurrences, assessing quality of life is necessary to
      provide a proper, comprehensive understanding of the outcome of surgery and other
      forms of treatment.

PMID- 16632982
TI  - [The development of irritable bowel syndrome after Shigella infection: 3 year
      follow-up study].
AB  - BACKGROUND/AIMS: Bacterial gastroenteritis seems to be a risk factor of irritable
      bowel syndrome (IBS). The incidence of post-infectious IBS (PI-IBS) was reported
      to be in the range of 7-31%, but few studies have reported long term follow-up
      results. So, we investigated the clinical course and prognosis of PI-IBS three
      years after shigella infection. METHODS: The subjects were recruited from our
      previous study, in which we investigated the incidence and risk factors of PI
      IBS. We had a questionnaire based on interview with 120 controls and 124 patients
      who had shigella infection three years ago. Both groups were evaluated for the
      presence of IBS, functional bowel disorders (FBD) except IBS before, one and
      three years after the infection, respectively. RESULTS: Ninety-five patients
      (76.6%) and 105 controls (87.5%) completed the questionnaire. In patients group,
      7 cases had IBS prior to infection (previous IBS), 12 cases (13.8%) had IBS after
      1 year (PI-IBS). Four cases developed IBS newly after 3 years (new IBS). Thirteen
      cases (14.9%) in patients and 4 cases (4.5%) in controls had IBS over 3 years (OR
      3.93: 1.20-12.86). The recovery rate over 3 years were 50.0% (2/4) in previous
      IBS and 25% (3/12) in PI-IBS. The incidence of PI-IBS after 3 years in previous
      FBD subjects was 28.6% and was 10.6% in normals (p<0.05). The female gender was a
      risk factor for FBD. CONCLUSIONS: Bacterial gastroenteritis is a trigger factor
      of IBS. About a quarter of PI-IBS patients are recovered over 3 years. Previous
      FBD except IBS is a risk factor after 3 years.

PMID- 16632983
TI  - [The decision-making value of magnetic resonance cholangiopancreatography in
      patients suspicious for pancreatobiliary diseases].
AB  - BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is an
      operator-dependent procedure and has significant procedure-related morbidity and
      mortality. Magnetic resonance cholangiopancreatography (MRCP) is a safe
      noninvasive method for pancreatobiliary imaging. The aims of this study were to
      evaluate the potential impact of MRCP on performing ERCP and to evaluate the
      decision-making value of MRCP in patients suspicious for pancreatobiliary
      diseases. METHODS: Two hundreds twelve patients (M:F 108:104, mean age 59.3 +/-
      13.7) who underwent MRCP due to clinical or sonographic suggesting
      pancreatobiliary disease were included. We divided patients into four groups
      according to their presumptive diagnosis: biliary stone (group 1), biliary tumor
      (group 2), gallstone pancreatitis (group 3) and other biliary diseases (group 4).
      RESULTS: Numbers of cases in group 1, 2, 3 and 4 were 145, 43, 17 and 7,
      respectively. In 144 cases (67.9%), ERCP was unnecessary and 76 cases (35.8%)
      required neither ERCP nor any other treatment. Thereafter, these cases were
      thought to be a patient group in whom the workload of performing ERCP could be
      reduced. CONCLUSIONS: MRCP can reduce the number and efforts doing ERCP and is
      helpful in decision-making for the treatment of pancreatobiliary disease.
      Therefore, MRCP could be the primary diagnostic tool before choosing ERCP.

PMID- 16632984
TI  - [A case of iatrogenic tension pneumoperitoneum following colonoscopy in a patient
      with cytomegalovirus colitis].
AB  - Perforation of the colon occurs in 0.2 to 2% of all colonoscopic examinations.
      The most common sites of perforation are rectosigmoid junction and cecal area.
      Colonic perforation, leading to tension pneumoperitoneum in most cases, may be
      caused by direct trauma or pressurized air. It should be suspected in patients
      with hypotension, tachycardia and tachypnea during or after the colonoscopy. An
      83-year-old woman was admitted due to pulmonary embolism and left cerebellar
      infarction. Colonoscopy was performed due to bloody diarrhea. She was diagnosed
      as cytomegalovirus (CMV) colitis. One week after the colonoscopy, colon
      perforation was incidentally found on ascending colon, and tension
      pneumoperitoneum occurred immediately after the procedure. The perforated site
      was primarily closed and the patient discharged 20 days later. Herein, we report
      a case of tension pneumoperitoneum following colonoscopy in a patient with CMV
      colitis.

PMID- 16632985
TI  - [A case of Salmonella liver abscess].
AB  - Liver abscess can be caused by bacterial, parasitic, or fungal infection. Amebic
      abscesses are more common, but pyogenic abscesses account for three quarters of
      hepatic abscess in developed countries. Most common pathogens of the pyogenic
      liver abscess are Escherichia coli, Klebsiella pneumoniae, Bacteroides,
      Enterococci, Streptococci, and Staphylococci. However, liver abscess caused by
      Salmonella species has rarely been reported. We experienced a case of Salmonella
      liver abscess which improved after antibiotic therapy and percutaneous drainage.
      The patient was 52 years-old man who had an episode of intermittent fever, chills
      and epigastric pain for 2 weeks. He was diagnosed as liver cirrhosis eight years
      ago and diabetes three years ago. Salmonella group D, non-typhi was cultured from
      blood and pus from the liver respectively at the same time. With percutaneous
      drainage and susceptible antibiotic therapy, liver abscess decreased in size with
      improvements in fever and abdominal pain.

PMID- 16632986
TI  - [A case of carcinoid tumor of the common bile duct].
AB  - Majority of malignant neoplasms arising from the extrahepatic bile duct are
      adenocarcinomas. Carcinoid tumors at this site are extremely rare. We report a 67
      year-old woman with malignant carcinoid tumor of the common bile duct. She
      presented with obstructive jaundice of 1 week's duration. Abdominal CT and ERCP
      revealed a common bile duct mass. She underwent Whipple's operation and was
      diagnosed as malignant carcinoid tumor histologically and immunohistochemically.

PMID- 16632988
TI  - [Will the diagnosis of functional gastrointestinal disorders be disappeared?].

PMID- 16632987
TI  - [Crohn's disease associated with IgA nephropathy].
AB  - Crohn's disease is a condition of chronic inflammation potentially involving any
      location of the alimentary tract from mouth to anus. Numerous extraintestinal
      manifestations can also be present. Urologic complications of inflammatory bowel
      disease are seen in up to 25% of patients, but renal parenchymal disease has been
      rarely reported. IgA nephropathy is recognized worldwide as a most common form of
      primary glomerulonephritis. Clinical manifestations vary, ranging from
      microscopic hematuria to nephrotic syndrome. Recently, IgA nephropathy associated
      with systemic diseases has been reported. We describe a case of a 22 year-old man
      with Crohn's disease associated with IgA nephropathy. At the age of 8 years,
      microscopic hematuria appeared. After fourteen years, he presented with melena,
      mild fever, recurrent oral ulcer, microscopic hematuria and proteinuria.
      Colonoscopic examination revealed characteristic features of Crohn's disease such
      as multiple ulcers. Microscopic findings showed superficial ulceration with small
      noncaseating granulomas. Renal biopsy revealed IgA nephropathy. The patient was
      treated with oral prednisolone, olsalazine, and metronidazole followed by
      maintenance therapy with sulfasalazine and azathioprine resulting in clinical
      improvement of Crohn's disease and IgA nephropathy.

PMID- 16632990
TI  - Incidence and outcome of biliary strictures after pancreaticoduodenectomy.
AB  - OBJECTIVE: This single-institution review examined the incidence of biliary
      stricture formation after pancreaticoduodenectomy (PD) for benign and malignant
      periampullary disease. BACKGROUND: The incidence and course of stricture of the
      hepaticojejunostomy have not been documented after PD. METHODS: Between January
      1995 and April 2003, 1595 patients underwent PD for periampullary disease (392
      benign, 1203 malignant). A retrospective analysis of a prospectively collected
      database was performed to determine the incidence of biliary stricture after PD.
      RESULTS: Forty-two of the 1595 patients (2.6%) who underwent PD developed
      postoperative jaundice secondary to a stricture of the biliary-enteric
      anastomosis. There was no difference in the incidence of biliary strictures after
      resection for benign (n = 10, 2.6%) or malignant disease (n = 32, 2.6%). The
      median time to stricture formation resulting in jaundice was 13 months (range, 1
      106 months) and was similar for patients with benign and malignant disease.
      Preoperative jaundice did not protect against biliary stricture formation. By
      univariate analysis, biliary strictures were associated with preoperative
      percutaneous biliary drainage (odds ratio [OR] = 2.11, P = 0.02) and
      postoperative biliary stenting (OR = 2.11, P = 0.013). Postoperative
      chemoradiotherapy in patients with malignant disease was not associated with
      stricture formation. All strictures were initially managed with percutaneous
      biliary balloon dilatation and stenting, and only 2 patients required redo
      hepaticojejunostomy. Recurrent neoplastic disease was discovered in only 3 of the
      32 patients (9%) with malignant disease. All 3 of these patients had
      cholangiocarcinoma as their initial diagnosis. CONCLUSIONS: Biliary stricture
      formation is an infrequent complication after PD and can be managed successfully
      with percutaneous biliary dilatation and short-term stenting in most patients.
      The only significant univariate predictors for biliary stricture formation were
      preoperative and postoperative percutaneous biliary drainage. The development of
      a biliary stricture in patients who have undergone PD for malignant disease is
      usually benign and should not be automatically attributed to anastomotic tumor
      recurrence.

PMID- 16632991
TI  - Endoscopic therapy for achalasia before Heller myotomy results in worse outcomes
      than heller myotomy alone.
AB  - OBJECTIVE: Heller myotomy has been shown to be an effective primary treatment of
      achalasia. However, many physicians treating patients with achalasia continue to
      offer endoscopic therapies before recommending operative myotomy. Herein we
      report outcomes in 209 patients undergoing Heller myotomy with the majority (74%)
      undergoing myotomy as secondary treatment of achalasia. METHODS: Data on all
      patients undergoing operative management of achalasia are collected
      prospectively. Over a 9-year period (1994-2003), 209 patients underwent Heller
      myotomy for achalasia. Of these, 154 had undergone either Botox injection and/or
      pneumatic dilation preoperatively. Preoperative, operative, and long-term outcome
      data were analyzed. Statistical analysis was performed with multiple chi and Mann
      Whitney U analyses, as well as ANOVA. RESULTS: Among the 209 patients undergoing
      Heller myotomy for achalasia, 154 received endoscopic therapy before being
      referred for surgery (100 dilation only, 33 Botox only, 21 both). The groups were
      matched for preoperative demographics and symptom scores for dysphagia,
      regurgitation, and chest pain. Intraoperative complications were more common in
      the endoscopically treated group with GI perforations being the most common
      complication (9.7% versus 3.6%). Postoperative complications, primarily severe
      dysphagia, and pulmonary complications were more common after endoscopic
      treatment (10.4% versus 5.4%). Failure of myotomy as defined by persistent or
      recurrent severe symptoms, or need for additionally therapy including redo
      myotomy or esophagectomy was higher in the endoscopically treated group (19.5%
      versus 10.1%). CONCLUSION: Use of preoperative endoscopic therapy remains common
      and has resulted in more intraoperative complications, primarily perforation,
      more postoperative complications, and a higher rate of failure than when no
      preoperative therapy was used. Endoscopic therapy for achalasia should not be
      used unless patients are not candidates for surgery.

PMID- 16632992
TI  - Laparoscopic myotomy for achalasia: predictors of successful outcome after 200
      cases.
AB  - OBJECTIVE: Laparoscopic myotomy is the preferred treatment of achalasia. Our
      objectives were to assess the long-term outcome of esophageal myotomy and to
      identify preoperative factors influencing the outcome. METHODS: Preoperative and
      long-term outcome data were collected from patients undergoing laparoscopic
      myotomy for achalasia at our institution. The primary endpoint of the study was
      the postoperative change (delta) in dysphagia score. This score was calculated by
      combining the frequency and the severity of dysphagia. Persistent postoperative
      dysphagia was defined as 1 standard deviation less than the mean delta score of
      all patients. Logistic regression was used to identify independent preoperative
      factors associated with successful myotomy. RESULTS: A total of 200 consecutive
      patients were included in the study. At a mean follow-up of 42.1 months, the mean
      delta dysphagia score was 7.1 +/- 2.6; therefore, the myotomy was considered
      successful when the delta score was >4.5. According to this definition, 170 (85%)
      patients achieved excellent dysphagia relief (responders). Responders had higher
      preoperative low esophageal sphincter (LES) pressure than nonresponders: 42.6 +/-
      13.1 versus 23.8 +/- 7.0 mm Hg (P = 0.001). High preoperative LES pressure
      remained an independent predictor of excellent response in the multivariate
      logistic regression model. Patients with LES pressure >35 mm Hg had an odds ratio
      of 21.3, making more likely to achieve excellent dysphagia relief after myotomy
      compared with those with LES pressure < or =35 mm Hg (odds ratio, 21.3; 95%
      confidence interval, 6.1-73.5, P = 0.0001). CONCLUSION: Laparoscopic myotomy can
      durably relieve symptoms of dysphagia. Elevated preoperative LES pressure
      represents the strongest positive outcome predictor.

PMID- 16632993
TI  - Intermediate-term outcomes with expanded criteria deceased donors in kidney
      transplantation: a spectrum or specter of quality?
AB  - OBJECTIVE: To compare intermediate-term outcomes in adult recipients of expanded
      criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney
      transplants at a single center using a standardized approach. SUMMARY BACKGROUND
      DATA: Expanded criteria donors (ECDs) are a source of kidneys that increase the
      donor organ pool, but the value of transplanting these kidneys has been
      questioned because of concerns regarding diminished survival and predicted poorer
      intermediate-term outcomes. METHODS: Over a 47-month period, we performed 244
      deceased donor kidney transplants into adult recipients, including 143 from SCDs
      and 101 from ECDs. Management algorithms were implemented to preserve nephron
      function, and recipient selection for an ECD kidney transplant was based on low
      immunologic risk. All patients received depleting antibody induction in
      combination with tacrolimus and mycophenolate mofetil. A total of 188 patients
      (77%) had at least a 1-year follow-up. RESULTS: ECDs were older, had a higher
      BMI, had an increased incidence of cerebrovascular brain death and preexisting
      donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P <
      0.01) compared with SCDs. Cold ischemic times were similar between groups, but
      more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney
      recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen
      mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD
      kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates
      were similar between groups with a mean follow-up of 24 months. The rates of
      delayed graft function (DGF), acute rejection, readmissions, operative
      complications, major infections, and resource utilization were comparable between
      groups. Renal function followed longitudinally was consistently better in SCD
      patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection,
      and graft loss (P < 0.05), but the effects were less pronounced in the ECD group.
      CONCLUSIONS: By appropriate donor and recipient profiling and the use of
      management algorithms to project and protect renal function, excellent
      intermediate-term outcomes can be achieved with ECD kidney transplants that are
      comparable to SCD kidney transplants.

PMID- 16632994
TI  - Productivity measures associated with a patient access initiative.
AB  - OBJECTIVE: To assess financial performance associated with a patient 7-day access
      initiative. BACKGROUND DATA: Patient access to clinical services is frequently an
      obstacle at academic medical centers. Conflicting surgeon priorities among
      academic, clinical, educational, and leadership duties often create difficulties
      for patient entry into the "system." METHODS: The scope and objectives were
      identified to be: design of a standard, simple new patient appointment process,
      design of a standard process in cases where an appointment is not available in 7
      days, use subspecialty team search capabilities, minimize/eliminate prescheduling
      requirements, centralize appointment scheduling, and creation and reporting of 7
      day access metrics. Following maturation of the process, the 7-day access metrics
      from the period July 2004 to December 2004 and January 2005 to June 2005 were
      compared with corresponding time periods from calendar years 2001, 2002, and
      2003. RESULTS: Payor mix was unaltered. The median waiting time for a new patient
      appointment decreased from 21 days to 10 days. When compared with calendar years
      2001, 2002, and 2003, respectively, the 2 periods of the 7-day access initiative
      in calendar years 2004 and 2005 were associated with significantly increased
      visits, new patients, operative procedures, hospital charges, and physician
      charges. CONCLUSIONS: Implementation of a 7-day access initiative can
      significantly increase financial productivity of general surgery groups in
      academic medical centers. We conclude that simplifying access to services can
      benefit academic surgical practices. Sustaining this level of productivity will
      continue to prove challenging.

PMID- 16632995
TI  - The Southern Surgical Association History of Medicine Scholarship presentation:
      Dr. Charles Drew, a surgical pioneer.
AB  - When one considers the circumstances of his birth, the barriers that he had to
      overcome, and his abbreviated life span (<46 years), a strong case can be made
      that Charles Drew, MD, CM, MDSc, was one of the most accomplished surgeons of the
      20th Century; yet many practitioners and instructors of the surgical sciences
      know little or nothing about him. There are others who have heard of him and
      still harbor popular misconceptions about the circumstances of his death that
      have been perpetuated by several media outlets. The Southern Surgical Association
      promotes a substantially more inclusive brand of surgical fellowship than it did
      during the lifetime of Dr. Drew. We believe that the membership would greatly
      appreciate knowing some of the details of Dr. Drew's life, particularly his major
      scientific contributions and his commitment to excellence in patient care, and in
      the training of young surgeons.

PMID- 16632996
TI  - Dietary fiber enhances a tumor suppressor signaling pathway in the gut.
AB  - OBJECTIVE: To determine whether sodium butyrate (NaB), a major short-chain fatty
      acid produced in the human gut by bacterial fermentation of dietary fiber,
      enhances transforming growth factor (TGF)-beta signaling and potentiates its
      tumor suppressor activity in the gut. SUMMARY BACKGROUND DATA: The molecular
      mechanisms by which dietary fiber decreases the risk of colon cancers are poorly
      characterized. TGF-beta is an important tumor suppressor in the gut and has many
      similar biologic activities as NaB. Therefore, we hypothesized that the chemo
      preventive effects of NaB are mediated in part by enhancing TGF-beta signaling
      and its tumor suppressor function in the gut. METHODS: The effects of NaB on
      Smad3 expression in rat intestinal epithelial (RIE-1) cells and 6 human colon
      cancer cell lines were examined. The effects of NaB on TGF-beta-induced Smad3
      phosphorylation and plasminogen activator inhibitor-1 (PAI-1) and cyclooxygenase
      2 (COX-2) gene expression were also examined in RIE-1 cells. Finally, the effects
      of NaB and TGF-beta on anchorage-independent growth were examined in Akt
      transformed RIE-1 cells. RESULTS: NaB induced Smad3 in RIE-1 cells and in 4 human
      colon cancer cell lines. NaB enhanced TGF-beta-induced Smad3 phosphorylation and
      potentiated TGF-beta-induced PAI-1 expression. NaB and TGF-beta synergistically
      inhibited anchorage-independent growth of Akt-transformed RIE-1 cells.
      CONCLUSIONS: These results demonstrate that NaB induces Smad3 and potentiates TGF
      beta signaling and its tumor suppressor activity in gut epithelial cells. Our
      data reveal a novel molecular mechanism that may explain in part the beneficial
      effects of dietary fiber in decreasing the risk of colon cancers.

PMID- 16632997
TI  - Patient safety in surgery.
AB  - BACKGROUND: Improving patient safety is an increasing priority for surgeons and
      hospitals since sentinel events can be catastrophic for patients, caregivers, and
      institutions. Patient safety initiatives aimed at creating a safe operating room
      (OR) culture are increasingly being adopted, but a reliable means of measuring
      their impact on front-line providers does not exist. METHODS: We developed a
      surgery-specific safety questionnaire (SAQ) and administered it to 2769 eligible
      caregivers at 60 hospitals. Survey questions included the appropriateness of
      handling medical errors, knowledge of reporting systems, and perceptions of
      safety in the operating room. MANOVA and ANOVA were performed to compare safety
      results by hospital and by an individual's position in the OR using a composite
      score. Multilevel confirmatory factor analysis was performed to validate the
      structure of the scale at the operating room level of analysis. RESULTS: The
      overall response rate was 77.1% (2135 of 2769), with a range of 57% to 100%.
      Factor analysis of the survey items demonstrated high face validity and internal
      consistency (alpha = 0.76). The safety climate scale was robust and internally
      consistent overall and across positions. Scores varied widely by hospital [MANOVA
      omnibus F (59, 1910) = 3.85, P < 0.001], but not position [ANOVA F (4, 1910) =
      1.64, P = 0.16], surgeon (mean = 73.91), technician (mean = 70.26),
      anesthesiologist (mean = 71.57), CRNA (mean = 71.03), and nurse (mean = 70.40).
      The percent of respondents reporting good safety climate in each hospital ranged
      from 16.3% to 100%. CONCLUSIONS: Safety climate in surgical departments can be
      validly measured and varies widely among hospitals, providing the opportunity to
      benchmark performance. Scores on the SAQ can serve to evaluate interventions to
      improve patient safety.

PMID- 16632998
TI  - National Surgical Quality Improvement Program (NSQIP) risk factors can be used to
      validate American Society of Anesthesiologists Physical Status Classification
      (ASA PS) levels.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      the American Society of Anesthesiologists' Physical Status (ASA PS)
      classifications and the other National Surgical Quality Improvement Program
      (NSQIP) preoperative risk factors. BACKGROUND: The ASA PS has been shown to
      predict morbidity and mortality in surgical patients but is inconsistently
      applied and clinically imprecise. It is desirable to have a method for validating
      ASA PS classification levels. METHODS: The NSQIP preoperative risk factors,
      including ASA PS, were recorded from a random sample of 5878 surgical patients on
      6 services between October 1, 2001 and September 30, 2003 at the University of
      Kentucky Medical Center. Mortality, morbidity, costs, and length of stay were
      obtained and compared across ASA PS levels. The ability of 1) ASA PS alone, 2)
      the other NSQIP risk factors, and, 3) all factors combined to predict outcomes
      was analyzed. A model using the other NSQIP risk factors was developed to predict
      ASA PS. RESULTS: ASA PS alone was a strong predictor of outcomes (P < 0.01).
      However, the other NSQIP risk factors were better predictors as a group. There
      was significant interdependence between the ASA PS and the other NSQIP risk
      factors. Predictions of ASA PS using the other factors showed strong agreement
      with the anesthesiologists' assignments. CONCLUSIONS: The NSQIP risk factors
      other than ASA PS can and should be used to validate ASA PS classifications.

PMID- 16632999
TI  - Transparent and open discussion of errors does not increase malpractice risk in
      trauma patients.
AB  - OBJECTIVE: We set out to determine if there is an increased medical malpractice
      lawsuit rate when trauma patient cases are presented at an open,
      multidisciplinary morbidity and mortality conference (M&M). INTRODUCTION: Patient
      safety proponents emphasize the importance of transparency with respect to
      medical errors. In contrast, the tort system focuses on blame and punishment,
      which encourages secrecy. Our question: Can the goals of the patient safety
      movement be met without placing care providers and healthcare institutions at
      unacceptably high malpractice risk? METHODS: The trauma registry, a risk
      management database, along with the written minutes of the trauma morbidity and
      mortality conference (M&M) were used to determine the number and incidence of
      malpractice suits filed following full discussion at an open M&M conference at an
      academic level I trauma center. RESULTS: A total of 20,749 trauma patients were
      admitted. A total of 412 patients were discussed at M&M conference and a total of
      seven lawsuits were filed. Six of the patients were not discussed at M&M prior to
      the lawsuit being filed. One patient was discussed at M&M prior to the lawsuit
      being filed. The incidence of lawsuit was calculated in three groups: all trauma
      patients, all trauma patients with complications, and all patients presented at
      trauma M&M conference. The ratio of lawsuits filed to patients admitted and
      incidence in the three groups is as follows: All Patients, 7 lawsuits/20,479
      patients (4.25 lawsuits/100,000 patients/year); M&M Presentation, 1 lawsuit/421
      patients (29.6 lawsuits/100,000 patients/year); All Trauma Complications, 7
      lawsuits/6,225 patients (14 lawsuits/100,000 patients/year). Patients with a
      complication were more likely to sue (P < 0.01); otherwise, there were no
      statistical differences between groups. CONCLUSIONS: A transparent discussion of
      errors, complications, and deaths does not appear to lead to an increased risk of
      lawsuit.

PMID- 16633000
TI  - Effects of hemorrhagic shock on adrenal response in a rat model.
AB  - INTRODUCTION: There is a documented association between critically ill patients
      who are in refractory shock and adrenal insufficiency. The underlying
      pathophysiology may be related to ischemia, necrosis, reperfusion, or
      resuscitative dilution. We hypothesize this blunted adrenal response is due to
      ischemia and necrosis of the adrenal parenchyma. METHODS: Thirty Sprague-Dawley
      rats were intravascularly catheterized and hemorrhagic shock induced to a mean
      arterial pressure of 65 mm Hg. After 4 hours of hypotension, fluid resuscitation
      was initiated with a crystalloid solution (Lactated Ringers). A control group
      underwent catheterization without hemorrhage. Serum corticosterone levels were
      measured and adrenal glands harvested for histologic evaluation of hemorrhagic
      necrosis. RESULTS: Baseline corticosterone was 30.8 ng/mL in control animals and
      35.3 ng/mL in hemorrhagic animals (P = 0.10). One hour after hemorrhage,
      corticosterone was maximally stimulated at 406.2 ng/mL and in control animals was
      35.0 ng/mL (P = 0.0001). In experimental animals after 4 hours of hypovolemia,
      corticosterone dropped to 308.9 ng/mL (P = 0.0001). At 6 hours, corticosterone
      levels dropped to 149.0 ng/mL in experimental animals (P = 0.0001). Adrenal
      microscopy showed 1.5+ hemorrhagic necrosis in experimental animals compared with
      0.0+ in controls (P = 0.004). CONCLUSION: Our model suggests that ischemia and
      necrosis of the adrenal glands may be responsible for the adrenal insufficiency
      seen in patients with hemorrhagic shock. Further research may enable clinicians
      to discern earlier which patients will benefit from adrenal corticoid
      replacement.

PMID- 16633001
TI  - Laparoscopic versus open gastric bypass for morbid obesity: a multicenter,
      prospective, risk-adjusted analysis from the National Surgical Quality
      Improvement Program.
AB  - OBJECTIVE: To compare laparoscopic versus open gastric bypass procedures with
      respect to 30-day morbidity and mortality rates, using multi-institutional,
      prospective, risk-adjusted data. SUMMARY BACKGROUND DATA: Laparoscopic Roux-en-Y
      gastric bypass for weight loss is being performed with increasing frequency,
      partly driven by consumer demand. However, there are no multi-institutional, risk
      adjusted, prospective studies comparing laparoscopic and open gastric bypass
      outcomes. METHODS: A multi-institutional, prospective, risk-adjusted cohort study
      of patients undergoing laparoscopic and open gastric bypass procedures was
      performed from hospitals (n = 15) involved in the Private Sector Study of the
      National Surgical Quality Improvement Program (NSQIP). Data points have been
      extensively validated, are based on standardized definitions, and were collected
      by nurse reviewers who are audited for accuracy. RESULTS: From 2000 to 2003, data
      from 1356 gastric bypass procedures was collected. The 30-day mortality rate was
      zero in the laparoscopic group (n = 401), and 0.6% in the open group (n = 955) (P
      = not significant). The 30-day complication rate was significantly lower in the
      laparoscopic group as compared with the open group: 7% versus 14.5% (P < 0.0001).
      Multivariate logistic regression analysis was performed to control for potential
      confounding variables and showed that patients undergoing an open procedure were
      more likely to develop a complication, as compared with patients undergoing an
      laparoscopic procedure (odds ratio = 2.08; 95% confidence interval, 1.33-3.25).
      Propensity score modeling revealed similar results. A prediction model was
      derived, and variables that significantly predict higher complication rates after
      gastric bypass included an open procedure, a high ASA class (III, IV, V),
      functionally dependent patient, and hypertension as a comorbid illness.
      CONCLUSIONS: Multicenter, prospective, risk-adjusted data show that laparoscopic
      gastric bypass is safer than open gastric bypass, with respect to 30-day
      complication rate.

PMID- 16633002
TI  - Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal
      anastomosis: a single institutional case-matched experience.
AB  - OBJECTIVE: To compare safety and short-term outcomes of 100 laparoscopic ileal
      pouch-anal anastomosis (IPAA) versus 200 conventional open IPAA patients. SUMMARY
      BACKGROUND DATA: Outcomes of laparoscopic IPAA (LAP-IPAA) have been incompletely
      characterized. Previous reports are characterized by small numbers of patients
      and rarely include case-matched or randomized trial methodology. This report
      describes 100 LAP-IPAA patients case matched to 200 open IPAA patients. METHODS:
      Between 1998 and 2004, 100 consecutive LAP-IPAA patients (75 laparoscopic
      assisted, 25 hand assisted) were identified and case matched to 200 open IPAA
      control patients by age, operation, gender, date of operation, and body mass
      index. Operative and postoperative outcomes at 90 days were compared. RESULTS: A
      total of 300 patients (180 female) with a median age of 32 years (range, 17-66
      years), and a median body mass index of 23 kg/m (range, 16-34 kg/m) underwent
      IPAA (100 LAP-IPAA, 200 open IPAA). Diagnosis (chronic ulcerative colitis 97%,
      familial adenomatous polyposis 3%) and previous operative history were equivalent
      between groups. One intraoperative complication occurred in each group. Overall,
      the laparoscopic conversion rate was 6%. Median operative time was longer for the
      LAP-IPAA group (333 minutes versus 230 minutes, P < 0.0001). LAP-IPAA patients
      had shorter median time to regular diet (3 versus 5 days), time to ileostomy
      output (2 versus 3 days), length of stay (4 versus 7 days), and decreased IV
      narcotic use (all P < 0.05. Postoperative morbidity was equivalent (LAP-IPAA =
      33%, open IPAA = 37%), mortality was nil, and readmission rates were equal (LAP
      IPAA = 21%, open IPAA = 22%). Reoperation was required in 3% of LAP-IPAA and 6.5%
      of open IPAA patients (P < 0.2) during the first 3 months. CONCLUSION: LAP-IPAA
      is equivalent to open IPAA in terms of safety and feasibility. In addition, LAP
      IPAA provides significant improvements in short-term recovery outcomes.

PMID- 16633003
TI  - Periampullary and pancreatic incidentaloma: a single institution's experience
      with an increasingly common diagnosis.
AB  - BACKGROUND: While incidental masses in certain organs have received particular
      attention, periampullary and pancreatic incidentalomas (PIs) remain poorly
      characterized. METHODS: We reviewed 1944 consecutive pancreaticoduodenectomies
      (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients
      (6% of all PDs) presented with an incidental finding of a periampullary or
      pancreatic mass. The PI patients were analyzed and compared with the rest of the
      cohort (NI, nonincidentaloma group, n = 1826). RESULTS: Thirty-one percent of the
      PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P <
      0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had
      little or no risk for malignant progression. The 3 most common diagnoses in the
      PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and
      pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall
      complication rate (55% versus 43%, P = 0.02), due in part to a significantly
      increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001).
      Patients in the PI group with malignant disease had a superior long-term survival
      (median, 30 months, P = 0.01) compared with patients in the NI group with
      malignant disease (median, 21 months). CONCLUSIONS: Incidentally discovered
      periampullary and pancreatic masses comprise a substantial proportion of patients
      undergoing PD. Roughly three fourths of these lesions are malignant or
      premalignant, and amenable to curative resection. Resected malignant PIs have
      favorable pathologic features as compared with resected malignant NIs, and
      resection of these early lesions in asymptomatic individuals is associated with
      improved survival, compared with patients with symptomatic disease.

PMID- 16633004
TI  - High eIF4E, VEGF, and microvessel density in stage I to III breast cancer.
AB  - OBJECTIVE: In a prospective trial, to determine if eIF4E overexpression in breast
      cancer specimens is correlated with VEGF elevation, increased tumor microvessel
      density (MVD) counts, and a worse clinical outcome irrespective of nodal status.
      SUMMARY AND BACKGROUND DATA: In vitro, the overexpression of eukaryotic
      initiation factor 4E (eIF4E) up-regulates the translation of mRNAs with long 5'
      untranslated regions (5'-UTRs). One such gene product is the vascular endothelial
      growth factor (VEGF). METHODS: A total of 114 stage I to III breast cancer
      patients were prospectively accrued and followed with a standardized clinical
      surveillance protocol. Cancer specimens were quantified for eIF4E, VEGF, and MVD.
      Outcome endpoints were cancer recurrence and cancer-related death. RESULTS: eIF4E
      overexpression was found in all cancer specimens (mean +/- SD, 12.5 +/- 7.6
      fold). Increasing eIF4E overexpression correlated with increasing VEGF elevation
      (r = 0.24, P = 0.01, Spearman's coefficient), and increasing MVD counts (r =
      0.35, P < 0.0002). Patients whose tumor had high eIF4E overexpression had shorter
      disease-free survival (P = 0.004, log-rank test) and higher cancer-related deaths
      (P = 0.002) than patients whose tumors had low eIF4E overexpression. Patients
      with high eIF4E had a hazard ratio for cancer recurrence and cancer-related death
      of 1.8 and 2.1 times that of patients with low eIF4E (respectively, P = 0.009 and
      P = 0.002, Cox proportional hazard model). CONCLUSIONS: In breast cancer
      patients, increasing eIF4E overexpression in the cancer specimens correlates with
      higher VEGF levels and MVD counts. Patients whose tumors had high eIF4E
      overexpression had a worse clinical outcome, independent of nodal status. Thus,
      eIF4E overexpression in breast cancer appears to predict increased tumor
      vascularity and perhaps cancer dissemination by hematogenous means.

PMID- 16633005
TI  - Gender-related differences in outcome for melanoma patients.
AB  - OBJECTIVE: To better understand the factors associated with the well-established
      gender difference in survival for patients with melanoma. SUMMARY BACKGROUND
      DATA: Gender is an important factor in patients with cutaneous melanoma. Male
      patients have a worse outcome when compared with females. The reasons for this
      difference are poorly understood. METHODS: This prospective multi-institutional
      study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow
      thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in
      all patients. Clinicopathologic factors, including gender, were assessed and
      correlated with disease-free survival (DFS), distant disease-free survival
      (DDFS), and overall survival (OS). RESULTS: A total of 3324 patients were
      included in the covariate analyses; 1829 patients had follow-up data available
      and were included in the survival analyses. Median follow-up was 30 months. On
      univariate analysis, men (n = 1906) were more likely than women to be older than
      60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor
      regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor
      location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P <
      0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant
      in the model. There was no difference in the rate of SLN metastasis between men
      and women (P = 0.37) on multivariate analysis. When factors affecting survival
      were considered, the prognosis was worse for men as validated by lower DFS (P =
      0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). CONCLUSIONS: Male gender is
      associated with a greater incidence of unfavorable primary tumor characteristics
      without an increased risk for nodal metastasis. Nonetheless, gender is an
      independent factor affecting survival.

PMID- 16633006
TI  - The long-term effects of gastric bypass on vitamin D metabolism.
AB  - OBJECTIVE: Alterations of the endocrine system in patients following Roux-en-Y
      gastric bypass (GBP) are poorly described and have prompted us to perform a
      longitudinal study of the effects of GBP on serum calcium, 25-hydroxy-vitamin-D
      (vitamin D), and parathyroid hormone (PTH). METHODS: Prospectively collected data
      were compiled to determine how GBP affects serum calcium, vitamin D, and PTH.
      Student t test, Fisher exact test, or linear regression was used to determine
      significance. RESULTS: Calcium, vitamin D, and PTH levels were drawn on 243
      patients following GBP. Forty-one patients had long-limb bypass (LL-GBP), Roux
      >100 cm, and 202 had short-limb bypass (SL-GBP), Roux < or =100 cm. The mean (+/
      SD) postoperative follow-up time was significantly longer in the LL-GBP group
      (5.7 +/- 2.5 years) than the SL-GBP group (3.1 +/- 3.6 years, P < 0.0001). When
      corrected for albumin levels, mean calcium was 9.3 mg/dL (range, 8.5-10.8 mg/dL),
      and no difference existed between LL-GBP and SL-GBP patients. For patients with
      low vitamin D levels (<8.9 ng/mL), 88.9% had elevated PTH (>65 pg/mL) and 58.0%
      of patients with normal vitamin D levels (> or =8.9 ng/mL) had elevated PTH (P <
      0.0001). In individuals with vitamin D levels <30 ng/mL, 55.1% (n = 103) had
      elevated PTH, and of those with vitamin D levels > or =30 ng/mL 28.5% (n = 16)
      had elevated PTH (P = 0.0007). Mean vitamin D levels were lower in patients who
      had undergone LL-GBP as opposed to those with SL-GBP, 16.8 +/- 10.8 ng/mL versus
      22.7 +/- 11.1 ng/mL (P = 0.0022), and PTH was significantly higher in patients
      who had a LL-GBP (113.5 +/- 88.0 pg/mL versus 74.5 +/- 52.7 pg/mL, P = 0.0002).
      There was a linear decrease in vitamin D (P = 0.005) coupled with a linear
      increase in PTH (P < 0.0001) the longer patients were followed after GBP.
      Alkaline phosphatase levels were elevated in 40.3% of patients and correlated
      with PTH levels. CONCLUSION: Vitamin D deficiency and elevated PTH are common
      following GBP and progress over time. There is a significant incidence of
      secondary hyperparathyroidism in short-limb GBP patients, even those with vitamin
      D levels > or =30 ng/mL, suggesting selective Ca malabsorption. Thus, calcium
      malabsorption is inherent to gastric bypass. Careful calcium and vitamin D
      supplementation and long-term screening are necessary to prevent deficiencies and
      the sequelae of secondary hyperparathyroidism.

PMID- 16633007
TI  - Anatomic location of breast cancer micrometastasis in sentinel lymph node
      predicts axillary status.

PMID- 16633008
TI  - Complicated diverticulitis: it is not yet time to rethink the rules!

PMID- 16633011
TI  - Positron emission tomography/computed tomography influences on the management of
      resectable pancreatic cancer and its cost-effectiveness.

PMID- 16633012
TI  - Immunologic benefits of spleen transplantation in the absence of graft-versus
      host disease.

PMID- 16633014
TI  - Translational studies in neurorehabilitation: from bench to bedside.
AB  - Stroke is the leading cause of adult disability in the western world. Consensus
      has built over the last few years regarding the usefulness of training to improve
      motor disability resulting from stroke. Until recently, there were no accepted
      strategies to enhance the beneficial effects of training. However, the
      combination of basic and clinical science data over the last few years is
      changing this picture, and is highly relevant to the field of
      neurorehabilitation. Human studies in both healthy individuals and patients after
      brain damage demonstrate as a proof of principle that somatosensory input,
      cortical stimulation, interhemispheric interactions, and pharmacologic
      interventions can modulate cortical plasticity in neurorehabilitation after
      stroke. These findings strongly suggest directions in the development of novel
      strategies to enhance training effects on motor recovery. The intent of this
      review is to describe these strategies, the basic science principles on which
      they are based, and the clinical applications that have emerged so far.

PMID- 16633015
TI  - Complex motor function in humans: validating and extending the postulates of
      Alexandr R. Luria.
AB  - OBJECTIVE: We used functional brain imaging to reevaluate Luria's postulates and
      to elaborate the neural circuitry underlying performance of complex motor tasks.
      BACKGROUND: The anatomic organization and physiologic functioning of the normal
      human motor system have great significance for understanding motor dysfunction
      and remediation in neurology. Working with victims of penetrating head injuries,
      noted Russian neuropsychologist Aleksandr R. Luria designed several tests of fine
      motor control to understand their difficulties with complex voluntary movements.
      This led to his postulates that such function involves the premotor cortices and
      their interaction with the parietal lobe. METHOD: Six healthy young adults
      performed the hand imitation, fist-scissors-gun, and piano key tasks during blood
      oxygen level-dependent functional magnetic resonance imaging at 3 T. RESULTS: All
      3 tasks revealed activation of both premotor and parietal cortices. Furthermore,
      while hand Imitation relied more on the ventral premotor area and right parietal
      lobe, fist-scissors-gun and piano key relied more on the supplementary motor
      cortex. CONCLUSIONS: We postulate that differences in task-dependent activations
      across these tasks relate to degrees of sequential movement, pacing, and
      imitation. These results uphold Luria's original hypotheses, and extend that work
      by providing a further characterization of the motor areas involved in complex
      motor behaviors.

PMID- 16633016
TI  - Hand motor recovery after stroke: tuning the orchestra to improve hand motor
      function.
AB  - The motor deficits after stroke are not only the manifestation of the injured
      brain region, but rather the expression of the ability of the rest of the brain
      to maintain function. After a lesion in the primary motor cortex, parallel motor
      circuits might be activated to generate some alternative input to the spinal
      motoneurons. These parallel circuits may originate from areas such as the
      contralateral, undamaged primary motor area, bilateral premotor areas, bilateral
      supplementary motor areas, bilateral somatosensory areas, cerebellum, and basal
      ganglia. Most importantly, the efferent, cortico-spinal output pathways must be
      preserved for a desired behavioral result. Most of the recovery of function after
      a stroke may represent actual relearning of the skills with the injured brain.
      The main neural mechanisms underlying this relearning process after stroke
      involve shifts of distributed contributions across a specific neural network
      (fundamentally the network engaged in skill learning in the healthy). If these
      notions are indeed correct, then neuromodulatory approaches, such as transcranial
      magnetic stimulation, targeting these parallel circuits might be useful to limit
      injury and promote recovery after a stroke. This paper reviews the stroke
      characteristics that can predict a good recovery and compensations across brain
      areas that can be implemented after a stroke to accelerate motor function
      recovery.

PMID- 16633017
TI  - Paretic hand in stroke: from motor cortical plasticity research to
      rehabilitation.
AB  - Research in neural plasticity of adult cortical representations brought hope of
      significant potential for further improvement in therapy after cerebrovascular
      stroke, but the same processes involved in plasticity also allow for maladaptive
      changes whether spontaneous or caused by inappropriate therapeutic manipulations.
      Within the extensive network of multiple and bilateral motor cortical and
      subcortical areas, this paper focuses on the primary motor cortex. We review
      selected data from humans and primates regarding its functional anatomy and the
      mechanisms of adaptive neuroplasticity in the presence of brain insults, and the
      impact of motor skill learning in normals and rehabilitation therapy in patients.
      The discussion centers on the potential impact of the mechanisms of motor cortex
      neuroplasticity, especially of the phenomenon of competition among primary motor
      cortical representations, on the rehabilitation of paretic hand and shoulder
      after stroke. Application of results from neurophysiology and functional brain
      imaging research into the clinical practice is in the initial stages and remains
      a challenge for the future. Nevertheless, even the available research provides an
      important message for clinical rehabilitation of stroke patients: the need to
      widen multimodal and interdisciplinary approaches to rehabilitation of the
      paretic hand.

PMID- 16633018
TI  - Motor cortex excitability in stroke before and after constraint-induced movement
      therapy.
AB  - OBJECTIVE: To investigate motor cortex excitability in stroke patients and
      explore excitability changes induced by an intense physiotherapy. METHODS: We
      studied 12 chronic stroke patients (6 cortical, 6 subcortical lesions) before and
      after participation in 12 days of constraint-induced movement therapy.
      Transcranial magnetic stimulation was applied to test intracortical inhibition
      (ICI), intracortical facilitation, silent periods, amplitudes of motor evoked
      potentials, and motor thresholds. Motor function was assessed by the Motor
      Activity Log, the Wolf Motor Function Test, and the Modified Ashworth Scale for
      spasticity. RESULTS: Motor evoked potential amplitudes and motor thresholds were
      inversely correlated, indicating that both parameters reflect the function of
      corticospinal pathways. Before therapy, a motor cortex disinhibition was found in
      the affected hemisphere. This disinhibition was stronger in patients with
      cortical lesions. The amount of disinhibition was correlated with the degree of
      spasticity. After therapy, ICI changes were more pronounced in the affected
      hemisphere compared with the unaffected side. Both ICI decreases and increases
      were observed. Motor function tests indicated an improvement in all patients.
      CONCLUSIONS: Motor cortical disinhibition is present in chronic stroke patients.
      Therapy-associated changes of motor cortex excitability mainly occur in the
      lesioned hemisphere by up-regulation or down-regulation of ICI. We replicate that
      constraint-induced movement therapy improves motor functions in the chronic stage
      after stroke.

PMID- 16633019
TI  - Application of the CIT concept in the clinical environment: hurdles,
      practicalities, and clinical benefits.
AB  - Basic neuroscience research on brain plasticity, motor learning, and recovery has
      stimulated new concepts in motor rehabilitation. Combined with the development of
      methodological goal standards in clinical outcome research, these findings have
      effectuated the introduction of a double-paradigm shift in physical
      rehabilitation: (a) the move toward evidence-based procedures and disablement
      models for the assessment of clinical outcome and (b) the introduction of
      training-based concepts that are theoretically founded in learning theory. A
      major drive for new interventions has further come from recent findings on the
      adaptive capacities of neural networks and their linkage to perception,
      performance, and long-term recovery. In this context, constraint-induced movement
      therapy, an intervention initially designed for upper-limb hemiparesis,
      represents the theoretically and empirically most thoroughly founded training
      concept. Several clinical trials on constraint-induced therapy (CIT) have shown
      its efficacy in higher functioning patients; however, the transfer of the
      treatment into standard health care seems slow. Survey research further suggests
      a rather poor acceptance of CIT among clinical staff and it seems that the
      implementation of CIT is hindered by barriers constructed of beliefs and
      assumptions that demand a critical and evidence-based discussion. Within this
      context, we have conducted a series of experiments on amended CIT protocols and
      their application in the clinical environment which addressed the following
      issues: (1) massed practice: are 6 hours of daily training inevitable to achieve
      clinical benefits? (2) practicality: what is feasible in the standard care
      setting and what are the clinical benefits achieved by "feasible compromise CIT
      protocols?" (3) apprehensions: are concerns on increased muscular tone and
      pathologic movement patterns justified, and (4) learned nonuse: is the assumption
      of "hidden" residual abilities valid so that it warrants the constraint
      condition? In the present paper, the key findings of these studies will be
      summarized and critically discussed.

PMID- 16633020
TI  - Functions of the mirror neuron system: implications for neurorehabilitation.
AB  - Mirror neurons discharge during the execution of hand object-directed actions and
      during the observation of the same actions performed by other individuals. These
      neurons were first identified in the ventral premotor cortex (area F5) and later
      on in the inferior parietal lobule of monkey brain, thus constituting the mirror
      neuron system. More recently, mirror neurons for mouth object-directed actions
      have also been found in the monkey. Several pieces of experimental data
      demonstrate that a mirror neuron system devoted to hand, mouth, and foot actions
      is also present in humans. In the present paper we review the experimental
      evidence on the role of the mirror neuron system in action understanding,
      imitation learning of novel complex actions, and internal rehearsal (motor
      imagery) of actions. On the basis of features of the mirror neuron system and its
      role in action understanding and imitation, we discuss the possible use of action
      observation and imitation as an approach for systematic training in the
      rehabilitation of patients with motor impairment of the upper limb after stroke.

PMID- 16633021
TI  - Causes and risk factors for graft failure in surgeries performed by physicians in
      fellowship training.
AB  - PURPOSE: To determine the incidence, causes, and risk factors of penetrating
      keratoplasty failure. METHODS: A retrospective study was carried out in 213
      penetrating keratoplasties (194 patients) between January 1995 and January 2001
      at the Cornea Section of the Ophthalmology Service at the School of Medicine,
      Federal University of Uberlandia MG, Brazil. Follow-up time for 213 surgeries
      ranged from 2 to 68 months (mean 29.05 +/- 17.17 months). RESULTS: Two hundred
      thirteen surgeries were evaluated, and 54 (25.3%) failed. Risk factors for
      developing graft failure were regraft [relative risk (RR) = 2.9734], trauma (RR =
      1.4602) and herpes (HSV) (RR = 1.3400). Patients with previous glaucoma (P <
      0.00001), previous ocular surgery (P < 0.0008), combined procedures (P < 0.001),
      and glaucoma after penetrating keratoplasty (P < 0.00001) had an increased the
      rate of graft failure. The main causes of graft failure were irreversible
      rejection (50%), glaucoma (20.3%), primary graft failure (16.6%), and infection
      (3.8%). CONCLUSION: Graft failure is a common problem in cornea transplantation.
      Etiology and pre- and postsurgical risk factors are important in the prognosis of
      keratoplasties.

PMID- 16633022
TI  - Histologic and ultrastructural changes in corneas with granular and macular
      dystrophy after excimer laser phototherapeutic keratectomy.
AB  - PURPOSE: The histologic changes after phototherapeutic keratectomy (PTK) in
      corneas with granular and macular dystrophy were studied. METHODS: We studied 3
      corneas of 2 patients (1 granular, 2 macular dystrophy), who underwent
      penetrating keratoplasty (PK) at 0.8, 2.16, and 3.25 years after PTK; and 11
      corneas (controls) from 10 PK patients (5 granular, 6 macular dystrophy) by light
      microscopy and by transmission electron microscopy. PTK was performed by using
      the Asclepion-Meditec MEL 60 excimer laser. RESULTS: After PTK the epithelium (15
      40 versus 5-100 microm), and the upper stromal collagen lamella thickness (50-75
      versus 50-100 microm) were less irregular than for the controls. In 1 eye
      (macular dystrophy) 10 months after PTK an acid mucopolysaccharide-positive band
      was detected in the subepithelial stroma, which could be removed by hyaluronic
      acid digestion. This fact suggests that it was "haze" formed after PTK, rather
      than a subepithelial recurrence of the dystrophy. All PTK corneas had deposits in
      the mid- and posterior stroma. Concerning controls, deposits were detected under
      the epithelium in all corneas. Electron microscopy of the study corneas revealed
      a mostly continuous basal lamina, occasionally forming projections into the
      subepithelial stroma, and large numbers of well-developed hemidesmosomes (5.2 +/-
      0.8 per microm membrane length) present at greater density than in the controls
      (3.5 +/- 0.8). CONCLUSIONS: In stromal dystrophies, PTK was effective in removing
      large subepithelial stromal plaques. There were no subepithelial recurrences, and
      hemidesmosome density was increased.

PMID- 16633023
TI  - Fungal keratitis at the new york eye and ear infirmary.
AB  - INTRODUCTION: This study was designed to review the clinical experience at our
      institution with fungal keratitis during a 16-year period. MATERIALS AND METHODS:
      A review of the clinical and microbiology records of the New York Eye and
      Infirmary identified 61cases of fungal keratitis in 57 patients between January
      1, 1987 and June 1, 2003. The medical records of all patients were
      retrospectively reviewed to better delineate patient demographics, risk factors,
      etiologic organisms, treatment, and outcomes. RESULTS: A total of 5083 positive
      corneal cultures were recorded'from January 1, 1987 to June 1, 2003. Sixty-one
      eyes in 57 patients (37 women) were positive for fungus (1.2%). Three'patients
      had bilateral simultaneous infections. Candida albicans accounted for 29 of 61
      cases (48%). Human immunodeficiency virus (HIV) seropositivity (15 eyes), chronic
      ocular surface disease (14 eyes), and trauma (7 eyes) were the most commonly
      associated risk factors. CONCLUSIONS: Our experience with fungal keratitis in the
      northeastern United States appears to be different than those reported from other
      areas of the United States. Serologic positivity for HIV and chronic ocular
      surface disease were the most common associated risk factors followed by trauma,
      herpes simplex keratitis, and contact lens use. Candida species predominated,
      whereas filamentous fungi were uncommon.

PMID- 16633024
TI  - Application of umbilical cord serum eyedrops for the treatment of dry eye
      syndrome.
AB  - PURPOSE: To investigate the efficacy of umbilical cord serum eyedrops for the
      treatment of severe dry eye syndrome. METHODS: Fifty-five eyes of 31 patients
      with severe dry eye syndrome were treated with umbilical cord serum eyedrops.
      Symptom scoring, tear film break-up time (BUT), Schirmer test, corneal
      sensitivity test, and corneal fluorescein staining were performed before and 1
      and 2 months after treatment, and conjunctival impression cytology was performed
      before and 2 months after treatment. The concentrations of epidermal growth
      factor (EGF), vitamin A, and transforming growth factor-beta (TGF-beta) in
      umbilical cord serum and normal peripheral blood serum were measured. RESULTS:
      Two months after treatment, significant improvement was observed in symptom score
      (from 3.07 +/- 0.54 to 0.96 +/- 0. 58), BUT (from 3.96 +/- 1.56 to 5.45 +/- 2.54
      seconds), and keratoepitheliopathy score (from 4.87 +/- 3.22 to 1.71 +/- 1.84) (P
      < 0.01). There was no statistically significant change in Schirmer and corneal
      sensitivity tests. In impression cytology, the grade of squamous metaplasia (from
      2.35 +/- 0.72 to 1.44 +/- 0.69) and goblet cell density (from 80.91 +/- 31.53 to
      154.68 +/- 43.06 cell/mm) improved significantly (P < 0.01). The mean
      concentrations of EGF, TGF-beta, and vitamin A were 0.48 +/- 0.09, 57.14 +/-
      18.98, and 230.85 +/- 13.39 ng/mL in umbilical cord serum and 0.14 +/- 0.03,
      31.30 +/- 12.86, and 372.34 +/- 22.32 ng/mL in peripheral blood serum,
      respectively. CONCLUSION: Umbilical cord serum contains essential tear
      components, and umbilical cord serum eyedrops are effective and safe for the
      treatment of severe dry eye syndrome.

PMID- 16633025
TI  - Superficial hypertrophic dendriform epitheliopathy: a follow-up series.
AB  - PURPOSE: To report the interval courses of previously reported cases of
      superficial hypertrophic dendriform epitheliopathy (SHDE) and to describe 3 new
      cases of this uncommon entity following penetrating keratoplasty. METHOD:
      Retrospective chart review. RESULTS: We report follow-up on 3 previously
      described cases of SHDE, including discussion of cases and their clinical course.
      All 3 patients had persistent surface abnormalities complicating graft success
      resulting in poor visual outcomes. Three new cases of SHDE are discussed with a
      summary of the ocular findings and treatment. All patients underwent multiple
      penetrating keratoplasties for recurrent graft failures resulting from chronic
      postkeratoplasty surface keratopathy. CONCLUSIONS: SHDE is a rare complication of
      penetrating keratoplasty that can lead to delayed healing, chronic derangement of
      the corneal surface, corneal scarring, and an increased risk of graft rejection.
      Understanding and recognizing this entity is crucial for maximizing graft
      outcomes. Further investigation of the pathogenesis is necessary for complete
      understanding and management of the disorder.

PMID- 16633026
TI  - Tear film lipid layer alterations in allergic conjunctivitis.
AB  - PURPOSE: To assess the alterations of the tear film lipid layer and tear
      functions in patients with seasonal allergic conjunctivitis (SAC) and to compare
      the results with healthy control subjects. METHODS: Seventy-eight eyes of 39
      consecutive patients diagnosed as SAC (mean age 32.6 years; 11 male, 28 female)
      as well as 20 eyes of 10 healthy control subjects (mean age 32.5 years; 6 male, 4
      female) underwent slit-lamp examinations, tear film breakup time measurements
      (BUT), corneal fluorescein stain scoring, Schirmer test, and tear film lipid
      layer interferometry. The 2 groups were then compared for the examined
      parameters. RAST and serum IgE level evaluations were also carried out in the
      patients to confirm the diagnosis of allergy. RESULTS: The mean BUT was 3.4 +/-
      1.5 seconds in patients with SAC compared with the mean value of 12.4 +/- 2.4
      seconds in the controls (P < 0.05). There were no significant differences in
      relation to Schirmer test values between the 2 groups; 78% of the patients with
      SAC had grade 3 or above dry eye change in tear film lipid layer interferometry,
      whereas none of the controls had an interferometry grade greater than 3 (grade 1
      2 normal; grade 3-4 dry eye; grade 5 severe dry eye). Eyes with SAC had
      significantly higher tear film lipid layer thickness ranges compared with the
      control eyes (P < 0.05). CONCLUSION: SAC was associated with advanced tear
      instability and thickening of the tear film lipid layer. Evaluation of the tear
      film lipid layer thickness might be useful in the assessment of the extent of dry
      eye disease and the treatment outcomes in patients with allergy.

PMID- 16633027
TI  - Quantitative evaluation of the early changes in ocular surface inflammation
      following MMC-aided papillary resection in severe allergic patients with corneal
      complications.
AB  - BACKGROUND: Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis
      (VKC) are chronic inflammatory allergic diseases that are associated with some
      common conjunctival and corneal complications.1 The clinical corneal
      manifestations of both entities may include superficial punctate keratitis,
      macroerosions, corneal ulceration, plaque formation, corneal neovascularization,
      and lipid infiltration. PURPOSE: To quantitatively evaluate the early ocular
      surface inflammation before and after mitomycin C (MMC)-aided papillary resection
      in severe allergy patients with corneal complications. METHODS: Three eyes with
      VKC and 5 eyes with AKC were included in this study. All eyes had cobblestone
      like papillae on the upper tarsal conjunctiva and corneal complications such as
      corneal ulcers, defect, or erosions that were refractory to conventional
      treatment of more than 2 weeks. Papillary resection with intraoperative 0.05% MMC
      application for 5 minutes on the palpebral conjunctiva was carried out in all
      eyes. Corneal and conjunctival findings were evaluated before and 1 week and 2
      weeks after surgery. Brush cytology (BC) and evaluation of tear eosinophilic
      cationic protein (ECP) levels by radioimmunoassay techniques were performed as
      well pre- and postoperatively. RESULTS: Corneal and conjunctival complications
      resolved in all patients within 7 days after resection. Postoperative tear ECP
      levels decreased significantly with papillary resection (P< 0.05). Concomitant
      brush cytology showed a significant decrease in the number of eosinophils and
      neutrophils following papillary resection (P < 0.05). CONCLUSION: MMC-aided
      papillary resection provided a dramatic decrease in ocular surface inflammation
      as evidenced by decrease in the number of inflammatory cells as well as tear ECP
      levels with a rapid improvement of clinical corneal and conjunctival findings.

PMID- 16633028
TI  - Prevention and treatment of corneal graft rejection: current practice patterns
      (2004).
AB  - PURPOSE: This study was designed to analyze current practice patterns in the
      prevention and treatment of corneal graft rejection and to compare these patterns
      with previously reported practices. METHODS: In January 2004, a survey addressing
      the routine postoperative management of corneal transplants and the treatment of
      various manifestations of corneal graft rejection was sent to members of The
      Cornea Society. RESULTS: Of the 396 surveys, 111 (28%) were returned and
      analyzed. All respondents used topical corticosteroids for routine postoperative
      management and treatment of endothelial graft rejection. Prednisolone, in brand
      or generic form, was used by 37 to 90% for routine management in various clinical
      scenarios and 81 to 91% for various manifestations of graft rejection at all time
      points; however, after 6 months, 12 to 26% used loteprednol etabonate for routine
      management. For routine management of high-risk grafts, 48% used topical
      cyclosporine in addition to prednisolone. Compared with previous surveys, the use
      of oral steroids significantly decreased for the routine management of high-risk
      corneal transplants, and the use of subconjunctival steroids decreased for the
      management of graft rejection. CONCLUSIONS: Topical prednisolone remains the
      mainstay for the prevention and treatment of corneal graft rejection; however,
      the role of newer agents, loteprednol etabonate and topical cyclosporine, is
      expanding.

PMID- 16633029
TI  - Central corneal iron deposition after myopic laser-assisted in situ
      keratomileusis.
AB  - PURPOSE: To describe central corneal iron deposition after myopic laser-assisted
      in situ keratomileusis (LASIK). METHODS: Patients visiting our outpatient clinics
      between February 2003 and January 2004 and displaying post-LASIK corneal iron
      deposits were retrospectively enrolled in the study. RESULTS: Forty-two eyes of
      24 patients developed corneal iron deposition after myopic LASIK surgery. All
      eyes displayed a small, spotty iron deposit located in the center of the corneal
      flap. The median interval between LASIK and diagnosis of corneal iron deposition
      was 22.5 months. The spherical equivalents of achieved correction ranged from
      4.00 D to 17.50 D. CONCLUSION: Spotty corneal iron deposition can develop in the
      center of the corneal flap after myopic LASIK surgery. Because it is
      asymptomatic, the condition may have been hitherto underestimated in patient
      populations.

PMID- 16633030
TI  - Longitudinal changes in corneal curvature in keratoconus.
AB  - PURPOSE: This study was designed to identify factors that predict longitudinal
      increases in corneal curvature as measured by the First Definite Apical Clearance
      Lens (FDACL) and flatter keratometric reading (Flat K) in keratoconus. METHODS:
      The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a long
      te rm evaluation of the natural history of keratoconus involving 1209 patients.
      This report uses 8 years of follow-up data from 1032 patients who had penetrating
      keratoplasty in neither eye at baseline and who provided enough data to compute
      the slope of the change with time in the FDACL or the Flat K. Outcome measures
      included the aforementioned slopes and whether the FDACL or the Flat K increased
      by 3.00 or more diopters (D) in at least 1 eye. RESULTS: At CLEK Study entry,
      patients were aged 38.9 +/- 10.8 years. Overall, 44.3% of them were women, and
      69.3% of them were white. The slope of the change in FDACL (0.18 +/- 0.60 D/y)
      and Flat K (0.20 +/- 0.80 D) during 8 years translates into expected 8-year
      increases of 1.44 D in FDACL and 1.60 D in Flat K. Increases of > or = 3.00 D in
      either eye had an 8-year incidence of 24.8% for FDACL and 24.1% for Flat K.
      Independent predictors of increased FDACL included younger age, poorer baseline
      high-contrast manifest refraction visual acuity, and non-white race. Younger age
      and poorer high-contrast manifest refraction visual acuity were independent
      predictors of a >3.00-D increase for both FDACL and Flat K. CONCLUSION: CLEK
      patients exhibited a slow but clear increase in corneal curvature. Younger age
      and poorer high-contrast manifest refraction visual acuity at baseline predicted
      the rate of change in corneal curvature.

PMID- 16633031
TI  - Avellino corneal dystrophy exacerbated after LASIK: scanning electron microscopic
      findings.
AB  - PURPOSE: To evaluate the ultrastructure of the cornea of Avellino corneal
      dystrophy (ACD) exacerbated by LASIK. METHODS: Three ACD patients with
      exacerbation of granular corneal deposits after LASIK underwent surgical removal
      of the corneal flap. The corneal flap was processed for scanning electron
      microscopy (SEM). RESULTS: SEM of all patients showed abnormal granular clusters
      in the fibrils of the corneal flap. CONCLUSION: Laser in situ keratomileusis
      induces corneal collagen abnormalities and adhesions of granular material in ACD
      patients.

PMID- 16633032
TI  - Use of polyurethane minisponges to collect human tear fluid.
AB  - PURPOSE: To characterize a method of tear collection based on the use of
      amphiphilic polyurethane absorbing minisponges. METHODS: Tear fluid was collected
      from 17 healthy volunteers. A preweighed polyurethane dry minisponge was laid on
      the margin of the lower eyelid. Once wet (5-10 minutes), the fluid was
      transferred to a preweighed Eppendorf tube after squeezing the sponge by
      centrifugation. The amount of fluid absorbed and fluid recovered were determined
      by reweighing the sponge and the tube after absorption and centrifugation steps,
      respectively. The fluid was qualitatively characterized by electrophoretic
      polypeptide profiling in Coomassie blue-stained SDS-polyacrylamide gels. RESULTS:
      Per eye, 14.6 +/- 5.3 microL tear fluid was collected. That volume was about 90%
      of the fluid absorbed by polyurethane minisponges, almost doubling the fraction
      recovered from other more hydrophilic absorbing polymers. Major bands
      characterizing the electrophoretic profile of this fluid were those of 79, 66,
      27, 18, and 14 kd. This profile was indistinguishable from that of tear fluid
      aspirated into glass microcapillaries. Tear fluid collected simultaneously from
      both eyes displayed the same profiles. Successive tear samples from a single eye
      showed the same profile except for the 66-kd band, which increased steadily as
      collection proceeded. Tear donors rarely complained of discomfort. CONCLUSIONS:
      Tear collection by absorbing polyurethane minisponges is highly advantageous in
      efficiency (recovery) and reproducibility (invariant electrophoretic polypeptide
      profiles). Tear donor comfort, simultaneous bilateral collection, and collections
      from several donors at once are additional major advantages of this collection
      method in studies involving single subjects and populations in health and
      disease.

PMID- 16633033
TI  - The effect of temperature on the antimicrobial activity of Optisol-GS.
AB  - PURPOSE: To determine the survival of different bacteria inoculated in Optisol-GS
      at refrigerated storage temperature (6 degrees C) and after subsequent warming to
      room temperature (19-22 degrees C). METHODS: Staphylococcus aureus, Enterococcus
      faecium, Streptococcus pneumoniae, and Pseudomonas aeruginosa were chosen from
      stock clinical isolates for inclusion in the study. The first group consisted of
      12 Optisol-GS vials. The second group consisted of 12 Optisol-GS vials containing
      corneas inappropriate for transplantation according to the Eye Bank Association
      of America (EBAA) protocols. Each group was inoculated with 3 concentrations of
      approximately 10, 10, and 10 colony-forming units (CFU)/mL of each bacterial
      species and then refrigerated per EBAA protocol. After 48 hours of refrigeration,
      all vials were placed at room temperature (RT) and counts were performed at 48,
      50 (2 hour RT), 54 (6 hour RT), 60 (12 hour RT), 72 (24 hour RT), and 96 (48 hour
      RT) hours. At 96 hours, the corneal tissue from 10 and 10 inocula were cultured.
      All samples underwent serial dilution, spiral plating on blood agar plates, and
      incubation at 35 degrees C. Viable colony counts were determined at 24 hours.
      RESULTS: Except for the 10 CFU/mL inocula of P. aeruginosa, all isolates were
      viable after 48 hours of refrigeration. Rapid bactericidal activity was observed
      against P. aeruginosa after 2 hours at RT, with complete sterilization by 6
      hours. The rate and extent of killing against S. aureus were influenced by the
      initial inoculum. Bactericidal activity was achieved after 2 hours at RT with 10
      CFU/mL of S. aureus versus 24 hours with the 10 inoculum. Of note, bactericidal
      activity was not observed against S. pneumoniae and E. faecium following 24 hours
      of storage at RT. The presence of corneal tissue did not affect viable counts,
      with counts from corneal tissue cultures reflecting the counts seen from Optisol
      GS after 48 hours at RT. CONCLUSIONS: The antimicrobial activity of Optisol-GS
      was reduced at refrigerated temperature and enhanced at RT. Bactericidal activity
      was not observed against E. faecium at either refrigerated temperature or RT.

PMID- 16633034
TI  - EMMPRIN and MMP-1 in keratoconus.
AB  - PURPOSE: This study was conducted to determine the eventual presence and activity
      of EMMPRIN (extracellular matrix metalloproteinase inducer CD147) and
      interstitial collagenase MMP-1 in the cornea of keratoconus patients and their
      eventual interrelationship. MMP-1 was chosen because it is able to degrade
      fibrillar corneal collagens type I and III and might therefore play a role in
      stromal thinning in keratoconus. METHODS: Immunohistochemical labeling of EMMPRIN
      and MMP-1 in relation to histopathological changes in 5 keratoconus patients and
      5 matched healthy controls was investigated. RESULTS: Relatively strong EMMPRIN
      expression was found in normal corneal epithelial cells, but moderate expression
      was also found in stroma. In keratoconus, EMMPRIN was found in all layers of
      cornea, especially in histopathologically altered areas. In normal cornea, MMP-1
      staining was weak and restricted to epithelial cells. In keratoconus, MMP-1
      expression was slightly augmented in epithelial cells and also appeared locally
      in a scattered manner in the stroma. The distribution of MMP-1 did not totally
      overlap with that of histologically apparent corneal damage and EMMPRIN
      expression. CONCLUSIONS: Both EMMPRIN and MMP-1 are upregulated in keratoconus,
      but MMP-1 may not be the only tissue destructive MMP upregulated by EMMPRIN as
      only EMMPRIN expression correlated topologically very well with corneal damage.

PMID- 16633035
TI  - Immunohistochemical findings after LASIK confirm in vitro LASIK model.
AB  - PURPOSE: To compare immunohistochemical findings in human donor corneas after
      successful laser in situ keratomileusis (LASIK) without clinical complications
      with a recently established human LASIK in vitro model. METHODS: Donor corneas
      with prior LASIK treatment were investigated. Cryostat sections were stained
      immunohistochemically for collagen types I, III, and VI and laminin and
      fibronectin. RESULTS: With light microscopy, the interface of the LASIK flap
      could hardly be detected. In all samples, fibronectin was consistently detected
      along the entire extent of the surgical wound. In contrast, collagen type III and
      laminin only stained the superficial portion of the LASIK incision site. Staining
      for collagen types I and VI showed no changes after LASIK. CONCLUSION: Histologic
      findings in donor corneas with prior LASIK treatment confirm histologic
      observations in a recently introduced human organ culture LASIK model. This
      strengthens the reliability of the latter LASIK model for further studies
      concerning wound healing after LASIK surgery.

PMID- 16633036
TI  - Top hat wound configuration for penetrating keratoplasty using the femtosecond
      laser: a laboratory model.
AB  - PURPOSE: To evaluate the mechanical stability and induced astigmatism of a
      modified multiplanar "top hat" wound configuration for full-thickness penetrating
      keratoplasty (PK) using the femtosecond laser as compared with PK in a laboratory
      model. METHODS: Eight human corneoscleral rims were mounted on an artificial
      anterior chamber. Four samples were assigned to the traditional PK group. Four
      samples underwent full-thickness keratoplasty with the femtosecond laser: a 9.0
      mm cylindrical cut was made from the anterior chamber into the stroma, followed
      by a ring-shaped (outer diameter 9.0 mm, inner diameter 7.0 mm) horizontal
      lamellar resection at two-thirds corneal depth and a 7.0-mm cylindrical cut from
      the lamellae to the corneal surface. Mechanical stability was evaluated after
      placement of the cardinal sutures and the running sutures. RESULTS: In the "top
      hat" PK group, wound leakage occurred at 19 +/- 3.36 mm Hg after placement of the
      cardinal sutures and at 86.25 +/- 9.74 mm Hg after placement of the running
      sutures. In the traditional PK group, leakage occurred at 0 +/- 0 mm Hg and 76.25
      +/- 20.98 mm Hg after placement of the cardinal sutures and running sutures,
      respectively. Both techniques induced steepening of the corneal curvature postop.
      The modified wound group showed a mean change in average K of 3.43 +/- 3.62 D,
      whereas the traditional PK group showed a mean change in average K of 3.21 +/-
      6.67 D. CONCLUSION: The femtosecond laser-produced "top hat" wound configuration
      for PK was found to be more mechanically stable than that produced by the
      traditional method.

PMID- 16633037
TI  - Differential expression of collagen types XVIII/endostatin and XV in normal,
      keratoconus, and scarred human corneas.
AB  - PURPOSE: This study was designed to clarify the expression of 2 closely related
      collagen (Col) types XVIII and XV, and the proteolytically derived endostatin
      fragment of ColXVIII in normal, keratoconus, and scarred human corneas. METHODS:
      Immunohistochemistry, in situ hybridization, immunoelectron microscopy, and
      Western immunoblotting were used for human corneal samples obtained from
      penetrating keratoplasty. RESULTS: In the normal cornea, ColXVIII was
      immunolocalized to the corneal and conjunctival epithelial basement membrane
      (EBM), Descemet s membrane, and the limbal and conjunctival capillaries.
      Immunoreaction for endostatin was otherwise similar, but it also was present in
      corneal epithelial cells. Western immunoblotting showed that normal cornea
      contains several endostatin fragments ranging from 20 to 100 kDa. ColXV was
      present in the EBM of the limbus and conjunctiva, but not in EBM of the clear
      cornea. In situ hybridization revealed that corneal basal epithelial cells were
      responsible for the synthesis of ColXVIII mRNA. Keratoconus cases were
      characterized by an irregular EBM immunoreactivity for ColXVIII and endostatin
      and patchy immunoreactivity beneath EBM. In scarred corneas, highly increased
      immunoreactivity for ColXVIII, endostatin, and ColXV was present within stroma.
      CONCLUSIONS: The results indicate that ColXVIII and ColXV are differentially
      expressed in normal human corneas. Constant expression of ColXVIII by corneal EBM
      suggests that it is an important structural molecule. Aberrant expression of
      ColXVIII, endostatin, and ColXV in keratoconus and scarred corneas emphasizes the
      active role these molecules in the wound healing process.

PMID- 16633038
TI  - Antibacterial analysis in vitro of ethyl-cyanoacrylate against ocular pathogens.
AB  - PURPOSE: To analyze the antimicrobial properties of ethyl-cyanoacrylate
      (Superbonder, Loctite, Brazil) in vitro in different microorganisms related to
      corneal infections. METHODS: We analyzed the following microorganisms: (1)
      Staphylococcus aureus (multiresistant); (2) S. aureus (ATCC 25923); (3) coagulase
      negative Staphylococcus; (4) Streptococcus pyogenes; (5) Streptococcus
      pneumoniae; (6) Pseudomonas aeruginosa (multiresistant); (7) P. aeruginosa (ATCC
      27853); (8) Escherichia coli (ATCC25922); and (9) Enterococcus faecalis (ATCC
      29212). One drop of the glue was dropped directly into the nutrient broth. The
      plates were incubated at 35 +/- 2 degrees C and its growth examined after 24
      hours. Bactericidal activity of the glue was verified by sampling inhibition
      zones when present. The samples were plated in blood agar an analyzed after 24
      and 48 hours. RESULTS: The ethyl-cyanoacrylate inhibited the growth of every gram
      positive microorganism tested and showed bactericidal effect over 70% for all of
      them. Among the gram-negative microorganisms, only the E. coli and the E.
      faecalis had its growth inhibited, and the bactericidal effect was 60% and 40%,
      respectively. CONCLUSION: The ethyl-cyanoacrylate has bacteriostatic and
      bactericidal action in vitro, mainly against gram-positive microorganisms.

PMID- 16633039
TI  - Use of nerve growth factor to treat congenital neurotrophic corneal ulceration.
AB  - PURPOSE: This study was designed to assess the efficacy of nerve growth factor in
      the treatment of neurotrophic corneal ulceration in a child with bilateral
      congenital corneal anesthesia secondary to trigeminal insufficiency. METHODS: A 5
      month-old child presented to the casualty department with a 2-week history of red
      eyes and right corneal ulceration. Slit-lamp examination showed a central defect
      in the right corneal epithelium with underlying stromal opacification, only mild
      conjunctival inflammation with slight decreased tear production, and otherwise
      apparently normal eyes. Initially this was investigated as an infected ulcer and
      treated for several weeks as herpetic ulceration with no beneficial effect.
      Further clinical examination demonstrated bilateral decreased corneal sensation
      along with decreased facial sensation in keeping with congenital trigeminal nerve
      insufficiency. Investigation with magnetic resonance imaging showed no obvious
      abnormality. Conservative treatment with lubricants resulted in progressive right
      corneal stromal loss, and no healing occurred in the left corneal ulcer.
      Bilateral large lateral tarsorrhaphies were performed. Despite this, the left
      corneal ulcer demonstrated no improvement and increasing stromal opacification
      was noted. Topical nerve growth factor (NGF) was then used to treat the left
      cornea and resulted in epithelial healing within 1 week. Treatment was continued
      for a further 10 days after epithelial healing. Despite conventional treatment on
      3 separate occasions, further epithelial breakdown occurred. Topical NGF
      treatment resulted in a rapid improvement and healing of the epithelial
      defect.'At present, the patient is receiving a 6-month continuous treatment plan
      of NGF. RESULTS: Persistent epithelial defects (PED) secondary to neurotrophic
      ulceration have responded to topical NGF on 3 separate occasions during a 2-year
      period. The corneal epithelium now remains intact, and the cornea has no
      vascularization; however, mild anterior stromal opacification has gradually
      increased despite prolonged NGF treatment. CONCLUSION: NGF seems to represent a
      safe and efficacious treatment option to restore the integrity of corneal
      epithelium in which there is congenital corneal anesthesia because of trigeminal
      insufficiency. However, this treatment alone is insufficient to prevent
      progressive anterior stromal opacification.

PMID- 16633040
TI  - Acanthamoeba keratitis in a 5-year-old boy without a history of contact lens
      usage.
AB  - PURPOSE: This study was designed to report a case of acanthamoeba keratitis in a
      5-year-old child without a history of trauma or contact lens usage. METHODS: The
      history, clinical presentation, diagnostic, and therapeutic approaches were
      reviewed. RESULTS: A 5-year-old child without any history of trauma or contact
      lens use was referred to our university clinic with an initial diagnosis of
      disciform herpetic keratitis. After 2 weeks of antibacterial and antiviral
      therapy, a corneal biopsy was performed for diagnostic purposes. The biopsy
      revealed acanthamoeba. Subsequently intensive therapy with chlorhexidine
      diacetate 0.02%, ketoconazole tb, hexamidine di-isethionate 0.1% was initiated.
      At the end of the first month, topical prednisolone acetate 1% was added to
      reduce inflammation, Chlorhexidine diacetate 0.02% and oral ketoconazole were
      discontinued, and hexamidine di-isethionate 0.1% was lowered to 4 x 1 and was
      administered for an additional 4 months. At the end of 5 months, all medications
      were withdrawn and amblyopia treatment was started. CONCLUSION: When dealing with
      keratitis in children, acanthamoeba should be considered even without history of
      contact lens usage or trauma.

PMID- 16633041
TI  - Eye banking error: report of a donor cornea with a soft contact lens left in
      place.
AB  - PURPOSE: To report the first known case of a donor cornea being examined and
      shipped with a soft contact lens in place. METHODS: Case Report. RESULTS: Surgery
      was cancelled, the two involved eye-banks were notified, and the patient
      underwent successful keratoplasty 2 days later. CONCLUSION: Eye banking is
      essential to the practice of Ophthalmology. Rarely, errors occur despite the
      strict protocols and procedures that have been instituted over the years. These
      errors force us to reevaluate and update those policies as technology rapidly
      advances. We present here the first reported case of donor ocular tissue being
      examined and then shipped with a contact lens on the cornea. It is possible that
      there are other errors that are not published. It behooves us to disclose these
      and to discuss any of these errors openly to allow us to maintain confidence in
      our local eye banks, and to help us practice the safest medicine possible for our
      patients.

PMID- 16633042
TI  - Long-term complications of iris-claw phakic intraocular lens implantation in
      Weill-Marchesani syndrome.
AB  - PURPOSE: This study was designed to report the long-term complications of iris
      claw phakic intraocular lens implantation in a patient with Weill-Marchesani
      syndrome. METHODS: Case report and literature review. RESULTS: A 26-year-old man
      with a history of glaucoma had bilateral phakic lens implantation for high myopia
      10 years previously. Two years later, the left implant dislocated and was
      repositioned. Slit-lamp examination of both eyes revealed phakic implants of the
      iris-claw variety. There were moderate iridocorneal adhesions in the areas in
      which the lens haptics pinched the iris in both eyes and moderate epithelial and
      stromal edema over the temporal one-third of the left cornea. The crystalline
      lenses were clear with 3+phacodonesis OU. Dilated fundus examinations revealed
      bilateral severe optic nerve cupping. Crystalline lens diameters were measured at
      7.5mm in the right eye and 8 mm in the left. Anterior chamber depths were 2.63 mm
      OD and 2.40 mm OS. Specular microscopy revealed central endothelial cell counts
      of 1133 and 587 cells/mm OD and OS, respectively. Axial lengths were 23.3 mm OD
      and 25 mm OS. Gonioscopic examination revealed bilateral angle closure with
      marked peripheral anterior synechiae. Based on our findings of short stature,
      shortened and thickened fingers, relatively normal axial length,
      microspherophakia, high myopia, and glaucoma, we diagnosed the patient with Weill
      Marchesani syndrome. CONCLUSION: Iris claw-lens phakic lenses may be an effective
      surgical alternative to correct high myopia in select patients; however, it may
      produce long-term complications in eyes with specific features.

PMID- 16633043
TI  - Peripheral interstitial keratitis: a novel manifestation of ocular mastocytosis.
AB  - PURPOSE: To report a case of peripheral interstitial keratitis in a patient with
      mastocytosis. METHODS: Clinical case description and immunohistologic examination
      of biopsied ocular tissue. RESULTS: A 22-year-old woman with biopsy-proven
      urticaria pigmentosa, a subset of mastocytosis, presented with an active
      peripheral interstitial keratitis with vascularization associated with foreign
      body sensation and itching. Biomicroscopy of the cornea showed deep corneal
      inflammatory infiltrates and midstromal vascularization adjacent to a region of
      superior bulbar conjunctiva, which was mildly chemotic and inflamed. Topical mast
      cell stabilizers and a short course of topical steroids produced dramatic
      resolution of the lesion. Biopsy of the erythematous conjunctiva adjacent to the
      area of corneal inflammation showed the presence of mast cells. CONCLUSION: This
      is the first case of corneal inflammatory infiltration in a patient with
      mastocytosis. Therapy for this condition consists of a combination of topical
      mast cell stabilizers, topical steroids, and systemic antihistaminic therapy.

PMID- 16633045
TI  - Amniotic membrane transplant.

PMID- 16633046
TI  - 5-aminosalicylate therapy is associated with higher 6-thioguanine levels in
      adults and children with inflammatory bowel disease in remission on 6
      mercaptopurine or azathioprine.
AB  - BACKGROUND: Small uncontrolled trials have suggested that 5-aminosalicylate (5
      ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with
      Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably
      through the inhibition of thiopurine methyltransferase (TPMT). We tested the
      theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6
      TGn levels in a large cohort of children and adults with CD or ulcerative colitis
      (UC). METHODS: A retrospective cohort study identified all children and adults
      treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were
      included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6
      MMP) levels had been obtained after 3 months of clinical remission at a stable
      dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking
      and those not taking 5-ASA medications through the use of linear regression
      models to identify and adjust for potentially confounding variables. RESULTS: Of
      the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA
      agents had higher mean 6-TGn levels after adjustment for confounding variables
      (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT
      heterozygosity was independently associated with higher 6-TGn levels (P = 0.01
      and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6
      MMP levels. CONCLUSIONS: We found that 5-ASA therapy is associated with higher 6
      TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not
      explain this effect because 5-ASA exposure did not affect 6-MMP levels. The
      observed association of CD with higher 6-TGn levels is novel and needs to be
      verified in prospective studies.

PMID- 16633047
TI  - Indeterminate colitis: a significant subgroup of pediatric IBD.
AB  - BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel
      disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or
      Crohn's disease (CD). Our aims are to determine the prevalence of IC in our
      pediatric patient population and to describe its clinical presentation, natural
      history,and disease distribution. METHODS: We performed a retrospective database
      analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD
      Center between 1996 and 2001. Patient demographics, including age, sex, and age
      at disease onset, were tallied. Disease distribution was identified on the basis
      of a review of all endoscopic, colonoscopic, histopathological, and radiological
      records. All of the patients were followed up clinically to determine the extent
      of disease progression on the basis of the initial diagnosis of IC. RESULTS:
      Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD,
      49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly
      younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients
      with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC
      (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at
      diagnosis, and the remaining 15 had left-sided disease that progressed to a
      pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial
      diagnosis of IC were reclassified to either CD or UC after a median follow-up of
      1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their
      diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS:
      IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than
      that observed in adults. Children with IC have an early age of disease onset and
      a disease that rapidly progresses to pancolitis. Longitudinal studies are needed
      to determine the clinical implications of this pediatric IBD subgroup.

PMID- 16633048
TI  - Associations of allelic variants of the multidrug resistance gene (ABCB1 or MDR1)
      and inflammatory bowel disease and their effects on disease behavior: a case
      control and meta-analysis study.
AB  - BACKGROUND: Allelic variants of the ATP-binding cassette, subfamily B member 1
      (ABCB1), also known as the multidrug resistance gene (MDR1) that encodes the
      membrane-bound efflux transporter P-glycoprotein 170 (PGP-170), have been
      associated with inflammatory bowel disease but with conflicting results. METHODS:
      The present study examined the association of ABCB1 C3435T and G2677T/A in a
      large British case-control cohort of 828 Crohn's disease, 580 ulcerative colitis
      (UC) cases, and 285 healthy controls. The effect of these variants was further
      examined with respect to phenotypic and epidemiological characteristics. A meta
      analysis was carried out of our results and those from 8 previously published
      association studies of the C3435T variant in inflammatory bowel disease. RESULTS:
      The 2677T allele was significantly increased in British UC cases compared with
      controls (45.2% vs. 39.6%; P = 0.034). In particular, the TT genotype was
      significantly associated with severe UC (odds ratio [OR] 1.90; 95% CI 1.01-3.55)
      and the use of steroids in UC (OR 1.77; 95% CI 1.08-2.88). No significant
      association was seen with C3435T and UC, Crohn's disease, or any clinical
      subgroup. A meta-analysis of 9 association studies of C3435T showed a significant
      association of the 3435T allele with UC (OR 1.12; 95% CI 1.02-1.23; P = 0.013)
      but not with CD. CONCLUSIONS: These results indicate that ABCB1 sequence variants
      are associated with a small increase in the risk of developing UC and may
      influence disease behavior.

PMID- 16633049
TI  - CC-type chemokine receptor 5-Delta32 mutation protects against primary sclerosing
      cholangitis.
AB  - BACKGROUND: Primary sclerosing cholangitis (PSC) is commonly associated with
      inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory
      destruction of biliary ducts. The pathogenesis of PSC remains unknown, but
      immunological, bacterial, viral, and toxic factors play a role in a genetically
      susceptible host. We hypothesized that CC-type chemokine receptor 5 (CCR5) would
      be an interesting candidate gene for susceptibility to PSC from its chromosomal
      location within the IBD susceptibility locus on 3p21, as well as from a
      functional perspective. We therefore investigated the role of the functional 32
      bp deletion in this gene (CCR5-Delta32) with regard to susceptibility to PSC.
      METHODS: A total of 110 patients with PSC, 56 with concomitant IBD (23 with
      Crohn's disease, 28 with ulcerative colitis, 5 with indeterminate colitis), were
      collected. All of the subjects were genotyped for CCR5-Delta32 with polymerase
      chain reaction amplification, followed by detection on ethidium bromide-stained
      agarose gel. Genotypes and allele frequencies were compared with a cohort of IBD
      patients without PSC (n = 400) and healthy control subjects (n = 362). RESULTS:
      The frequency of the CCR5-Delta32 mutation in PSC (6.8%) was significantly lower
      compared with IBD (12.6%; P = 0.016) and healthy control subjects (12.2%, P =
      0.026), suggesting a protective effect of this mutation on PSC. None of the PSC
      patients with severe disease necessitating liver transplantation (n = 17) carried
      CCR5-Delta32. CONCLUSIONS: Because an intact CCR5 receptor is needed for
      internalization of specific pathogens and homing of memory T lymphocytes to the
      liver, we hypothesize that a deficient expression of this receptor resulting from
      the CCR5-Delta32 variant may protect against PSC.

PMID- 16633050
TI  - Unique dietary-related mouse model of colitis.
AB  - BACKGROUND: A high-fat diet is a risk factor for the development of inflammatory
      bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic
      contents in response to a high-fat diet. Thus, an elevated level of DOC in the
      colonic lumen may play a role in the natural course of development of IBD.
      METHODS: Wild-type B6.129 mice were fed an AIN-93G diet, either supplemented with
      0.2% DOC or unsupplemented and sacrificed at 1 week, 1 month, 3 months, 4 months,
      and 8 months. Colon samples were assessed by histopathological,
      immunohistochemical, and cDNA microarray analyses. RESULTS: Mice fed the DOC
      supplemented diet developed focal areas of colonic inflammation associated with
      increases in angiogenesis, nitrosative stress, DNA/RNA damage, and proliferation.
      Genes that play a central role in inflammation and angiogenesis and other related
      processes such as epithelial barrier function, oxidative stress, apoptosis, cell
      proliferation/cell cycle/DNA repair, membrane transport, and the ubiquitin
      proteasome pathway showed altered expression in the DOC-fed mice compared with
      the control mice. Changes in expression of individual genes (increases or
      reductions) correlated over time. These changes were greatest 1 month after the
      start of DOC feeding. CONCLUSIONS: The results suggest that exposure of the
      colonic mucosa to DOC may be a key etiologic factor in IBD. The DOC-fed mouse
      model may reflect the natural course of development of colitis/IBD in humans, and
      thus may be useful for determining new preventive strategies and lifestyle
      changes in affected individuals.

PMID- 16633051
TI  - Pain and mechanical properties of the rectum in patients with active ulcerative
      colitis.
AB  - BACKGROUND: The pain, urgency, and incontinence in ulcerative colitis may be
      related to changes in viscoelastic properties of the gut wall or to alterations
      of the sensory pathways. In the present study, we used an advanced rectal probe
      to study the mechanosensory and smooth muscle properties in patients with active
      disease. METHODS: Nine patients with ulcerative colitis (mean age 39.5 years)
      with exacerbation limited to the rectum and sigmoid colon and 17 age-matched
      healthy subjects were included. The rectum was distended before and after
      pharmacological relaxation of the smooth muscle until moderate pain was reported,
      and the cross-sectional area, volume, pressure, tension, and strain were
      computed. To investigate central integration of a tonic stimulus, the bag was
      finally distended to the pain threshold; then, the cross-sectional area was held
      constant for 2 min. RESULTS: The patients were hypersensitive to mechanical
      stimuli as assessed by the cross-sectional area (F = 21.7; P < 0.001). There were
      no differences in compliance or stiffness between the 2 groups, but the
      hypersensitivity was abolished after muscle relaxation. Together with the muscle
      analysis, this finding demonstrated that the smooth muscles were tonically
      contracted in the inflamed rectum, resulting in a decreased rectal circumference.
      The tonic distensions did not evoke central integration of the pain response,
      indicating that hyperalgesia is more likely related to peripheral factors.
      CONCLUSIONS: Patients with active ulcerative colitis have hypersensitivity and
      increased tone of the smooth muscles, which may explain the symptoms. Drugs that
      affect smooth muscle contraction may be helpful in difficult cases.

PMID- 16633052
TI  - Predicting the Crohn's disease activity index from the Harvey-Bradshaw Index.
AB  - BACKGROUND: The Crohn's Disease Activity Index (CDAI) was developed in the 1970s
      to assess the degree of illness in individuals with Crohn's disease and has since
      been used widely in clinical trials of the condition. The Harvey-Bradshaw Index
      (HBI) is a simplification of the CDAI, designed to make data collection and
      computation easier. It is purported, on the basis of a 0.93 correlation
      coefficient, to give "essentially the same information." However, correlation is
      an incomplete way to assess sameness, and this study aimed to develop a method
      for predicting CDAI from HBI values, including relevant prediction limits.
      MATERIALS AND METHODS: Data used in developing both indexes were combined. Single
      visits of 224 patients with Crohn's disease were plotted on a scattergram. HBI
      values seen were integers from 0 through 19. Mean and standard deviation of CDAI
      were determined for each HBI value that included a sufficient number of patients.
      Standard deviation of CDAI showed a linear increase with increasing HBI.
      Therefore, regression of CDAI on HBI was weighted on the inverse of the estimated
      CDAI standard deviation. RESULTS: Regression predicted a 27-CDAI-unit increase
      for each HBI unit. Calculated 95% prediction limits were almost straight,
      diverging lines, bracketing 95% of observations. A table gives central tendency
      and 95% prediction limits of CDAI for any HBI, as well as key clinical
      benchmarks. CONCLUSIONS: There is a good but far from perfect relationship
      between CDAI and HBI. CDAI is preferred for clinical trials; HBI is easier to
      use.

PMID- 16633053
TI  - Revisiting the immunomodulators tacrolimus, methotrexate, and mycophenolate
      mofetil: their mechanisms of action and role in the treatment of IBD.
AB  - Inflammatory bowel diseases (IBDs) are thought to result from unopposed immune
      responses to normal gut flora in a genetically susceptible host. A variety of
      immunomodulating therapies are applied for the treatment of patients with IBDs.
      The first-line treatment for IBDs consists of 5-aminosalicylate and/or
      budesonide. However, these first-line therapies are often not suitable for
      continuous treatment or do not suffice for the treatment of severe IBD. Recently,
      efforts have been made to generate novel selective drugs that are more effective
      and have fewer side effects. Despite promising results, most of these novel drugs
      are still in a developmental stage and unavailable for clinical application. Yet,
      another class of established immunomodulators exists that is successful in the
      treatment of inflammatory bowel diseases. While waiting for emerging novel
      therapies, the use of these more established drugs should be considered.
      Furthermore, one of the advantages of using established immunomodulators is the
      well-documented knowledge on the long-term side effects and on the mechanisms of
      action. In this review, the authors discuss 3 well-known immunomodulators that
      are being applied with increased frequency for the treatment of IBD: tacrolimus,
      methotrexate, and mycophenolate mofetil. These agents have been used for many
      years as treatment modalities for immunosuppression after organ transplantation,
      for the treatment of cancer, and for immunomodulation in several other immune
      mediated diseases. First, this review discusses the potential targets for
      immunomodulating therapies in IBDs. Second, the immunomodulating mechanisms and
      effects of the 3 immunomodulators are discussed in relationship to these
      treatment targets.

PMID- 16633054
TI  - Outcomes of placebo therapy in inflammatory bowel disease.
AB  - Placebo is important in assessing drug response, particularly in diseases
      characterized by spontaneous periods of acute exacerbation and quiescence.
      Randomized, placebo-controlled trials are the most objective means of evaluating
      drug efficacy, although the conduct of such clinical trials may not always be
      practical or ethical in all disease states. In inflammatory bowel disease (IBD),
      most patients experience intermittent episodes of active disease alternating with
      variable periods of remission. Thus, development of new medical therapies for IBD
      requires proof of superiority to placebo or alternative therapies. In this
      regard, knowledge of the outcomes of patients receiving placebo therapy and their
      influencing factors is important for proper study design and meaningful results.
      Such knowledge also is essential for interpreting results of open-label studies
      often necessary before randomized controlled trials can be conducted. In
      addition, the disease course of placebo-treated patients in clinical trials of
      IBD serves as an approximation of the natural history of these patients. The
      knowledge of placebo response in these patients provides clinicians with an
      important piece of information in prognosticating and making management
      decisions. This review presents our current knowledge of placebo therapy in IBD.
      Specifically, the existing literature on the outcomes and predictors of outcomes
      in patients receiving placebo therapy in clinical trials of IBD is reviewed.

PMID- 16633055
TI  - Myopericarditis and mitral insufficiency associated with ulcerative colitis
      treated with mesalazine.

PMID- 16633056
TI  - Role of infliximab in ulcerative colitis: further questions.

PMID- 16633057
TI  - Rifaximin for active ulcerative colitis.

PMID- 16633058
TI  - Successful infliximab therapy for oral Crohn's disease.

PMID- 16633059
TI  - Immunohistochemical and functional biomarkers of value in female genital tract
      lesions.
AB  - There has been a marked expansion in the literature pertaining to the use of
      immunohistochemical markers in female genital tract pathology, especially with
      regard to diagnosis. This review provides a survey of the antibodies commonly
      used in the diagnosis of gynecological lesions grouped as to function or type.
      Prognostic or predictive markers are also discussed where appropriate, although
      few of these are of value in everyday practice. It is stressed that when
      immunohistochemistry is used diagnostically, panels of markers provide better
      information than reliance on a single antibody.

PMID- 16633060
TI  - Ezrin promotes ovarian carcinoma cell invasion and its retained expression
      predicts poor prognosis in ovarian carcinoma.
AB  - The majority of patients diagnosed with ovarian carcinoma are classified as being
      in advanced stage of disease. In a situation of cancer spread throughout the
      abdominal cavity, a successful curative treatment is difficult to achieve.
      Therefore, preventing binding of tumor cells to the mesothelium is crucial for
      patients' outcome. One important mechanism is the interaction between hyaluronic
      acid and the CD44 receptor with its submembrane linking complex. This consists of
      ezrin, radixin, and moesin and connects the CD44 receptor with the cytoskeleton.
      To assess the role of ezrin and moesinfor ovarian carcinoma progression, we
      analyzed ovarian carcinoma samples from 105 patients for expression of ezrin and
      moesin by immunohistochemistry and correlated these data with several
      clinicopathological parameters. To elucidate the functional importance of ezrin
      and moesin, their expression was inhibited in SKOV-3 cells by RNA interference.
      Ezrin and moesin were strongly expressed in 49 and 48% of ovarian carcinoma
      samples, respectively, and their presence correlated with reduced overall
      survival in univariate analysis (ezrin, p=0.0189; moesin, p=0.0351). In
      multivariate analysis (including FIGO stage, residual tumor, histological type,
      and Silverberg grading), ezrin still remained significant as an independent risk
      factor (relative risk, 2.39; p=0.012). In SKOV-3 cells, siRNA against ezrin but
      not moesin inhibited in vitro invasion. These data imply that ezrin is necessary
      for tumor cell invasion, and the better prognosis of ovarian carcinomas lacking
      ezrin is probably related to their impaired invasion.

PMID- 16633061
TI  - Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells
      and for ovarian cancer cases of longer survival rates.
AB  - High cytoplasmic expression of maspin was described in ovarian cancers of shorter
      survival rates. Until now, no relationship has been described between expression
      of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at
      examining the relationship between expression of maspin, detected by
      immunohistochemistry and clinical response to cisplatin in ovarian cancer cases
      as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines.
      The analyzes were performed on 73 samples of ovarian cancer and on A2780P,
      A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and
      SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells
      significantly correlated with cisplatin sensitivity. A significantly shorter
      overall survival and progression-free survival was associated with lower
      cytoplasmic maspin expression at first-look laparotomies and nuclear maspin
      expression and secondary cytoreductions. Higher nuclear maspin at first-look
      laparotomies expression was specific for cases of complete response. In the
      study, the elevated expression of maspin was shown to be typical for cisplatin
      sensitive ovarian cancers.

PMID- 16633062
TI  - Increasing expression of extracellular matrix metalloprotease inducer in ovary
      tumors: tissue microarray analysis of immunostaining score with
      clinicopathological parameters.
AB  - Ovary cancer invasion is responsible for both local tissue destruction and
      distant metastasis. Invasion is largely mediated by matrix metalloproteases that
      are thought to be induced by tumor cell-derived extracellular matrix
      metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized
      that EMMPRIN isoverexpressed in ovary tumors. Immunohistochemical analysis of
      EMMPRIN was performed in tissue microarrays of ovary neoplasms including 84 cases
      of serous adenocarcinoma, 23 cases of mucinous adenocarcinoma, 10 cases of
      endometrioid adenocarcinoma, 12 cases of yolk sac tumor, 12 cases of clear cell
      carcinoma, 8 cases of dysgerminoma, 8 cases of granulosa cell tumor, 6 cases of
      transitional cell carcinoma, and 6 cases of Brenner tumor. All malignant ovary
      tumors showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN
      scores in malignant ovary tumors were significantly higher than their nontumor
      counterparts (313+/-28 for serous adenocarcinoma; 308+/-25 for mucinous
      adenocarcinoma; 187+/-19 for endometrioid adenocarcinoma; 265+/-23 for yolk sac
      tumors; 87+/-13 for clear cellcarcinoma; 126+/-15 for dysgerminoma; 243+/-26 for
      granulosa cell tumor; 87+/-16 for transitional cell carcinoma). The EMMPRIN score
      was significantly higher in serous adenocarcinomas than in serous adenomas and
      serous borderline tumors and was correlated with nodal stage. Our findings show
      for the first time that EMMPRIN is overexpressed in all malignant ovary tumors.

PMID- 16633063
TI  - Krukenberg tumor of renal pelvic origin: report of a case with selected comments
      on ovarian tumors metastatic from the urinary tract.
AB  - Metastatic tumors to the ovary are infrequently of urinary tract origin. In
      approximate descending order of frequency, this subset of secondary ovarian
      neoplasms includes renal cell carcinoma, transitional cell carcinoma of the
      urinary bladder, and urachal adenocarcinomas. These tumors usually raise a
      differential in turn of primary ovarian clear cell, transitional cell, or
      mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the
      bladder have shown the features of a Krukenberg tumor. We report the case of a 74
      year old woman with bilateral Krukenberg tumors metastatic from a primary renal
      pelvic transitional cell carcinoma with glandular and signet-ring cell
      differentiation. This unique case reinforces that tumors with signet-ring cell
      morphology have a propensity to metastasize to the ovary, and indicates that
      renal pelvic carcinoma rarely may be the source of Krukenberg tumors.

PMID- 16633064
TI  - Ovarian primary primitive neurectodermal tumor coexisting with endometrioid
      adenocarcinoma: a case report.
AB  - We report an unusual case of a 78-year-old woman with primary ovarian tumor that
      consisted of primitive neurectodermal tumor and endometrioid adenocarcinoma. The
      patient presented with abdominal pain and weight loss and had disseminated
      disease at her initial presentation. She was treated with debulking surgery
      followed by chemotherapy. The patient was still asymptomatic at the 6-month
      follow-up.

PMID- 16633065
TI  - Transtubal spread of serous adenocarcinoma of the endometrium: an underrecognized
      mechanism of metastasis.
AB  - Most endometrial carcinomas metastasize by invading myometrial lymphatics and
      spreading to regional lymph nodes. However, uterine serous carcinomas (USCs)
      metastasize frequently to peritoneal surfaces even when only minimally invasive.
      This study examines the methods of spread and the role of retrograde transtubal
      spread. Eighty-seven USCs treated by hysterectomy were identified. Primary
      peritoneal cases and cases with significant ovarian involvement were excluded.
      Eighty (92%) cases were pure serous, and the remainder had at least 25% serous
      histology. Fifty-four of 87 (62%) had extrauterine spread at hysterectomy, most
      commonly to peritoneal surfaces and sometimes to the pelvic lymph nodes. Twenty
      six of 54 (48%) cases had no lymphatic/vascular (LV) invasion and 18/54 (33%) had
      no myometrial invasion. Eleven of these 54 (20%) patients with metastases lacked
      both myometrial and LV invasion, and the metastases involved the peritoneal
      surface more often than the lymph nodes (p<0.001). Three of the 11 cases had
      tumor clusters in the fallopian tube lumen. Another 13 cases also had clusters of
      tumor within the fallopian tube lumen, and all 16 cases had peritoneal spread
      (p<0.001). Extrauterine spread correlated highly with LV invasion (p<0.001) but
      not with the presence or depth of myometrial invasion. Retrograde transtubal
      implantation as well LV invasion are two important mechanisms by which USC
      spreads; all cases with tumor clusters in the fallopian tube lumen had peritoneal
      spread. This explains the phenomenon whereby patients with serous carcinomas
      confined to the endometrium and lacking LV invasion have widespread metastases to
      the peritoneum.

PMID- 16633066
TI  - Expression pattern of osteopontin in endometrial carcinoma: correlation with
      expression of the adhesion molecule CEACAM1.
AB  - Osteopontin (OPN) and CEACAM1 have diverse biological functions in the uterus and
      placenta throughout the estrous cycle and pregnancy and have been shown to
      interact with integrin beta3. OPN is a glycoprotein of the extracellular matrix,
      which has been shown to mediate cellular migration and invasion and to contribute
      to tumorigenesis in several types of cancers. Recently we showed the expression
      pattern of OPN in gestational trophoblastic tumors. CEACAM1 is an adhesion
      molecule of the carcinoembryonic antigen family that we have recently found to be
      expressed in endometrial cancer and that has been shown to be down-regulated in
      colorectal, prostate, and breast cancer. In this study, immunohistochemistry and
      immunofluorescence with specific antibodies were performed on a series of 20
      normal endometrial samples, 17 endometrial hyperplasias, and 43 endometrial
      carcinomas (28 endometrioid, 10 serous, and 5 clear cell carcinomas) to
      investigate the expression pattern and cell-type specific localization of OPN and
      to correlate it with the expression of CEACAM1. In addition, Western blot was
      performed on normal human endometrium and endometrial neoplasia. Strong OPN
      expression with a consistent cytoplasmic localization in epithelial glandular
      cells was observed in the normal human endometrium in 80% of the samples of the
      proliferative and secretory phase (score 8-12). Similar results could be found in
      endometrial hyperplasias. Strong expression of OPN could be observed in 29
      (67.4%) of the 43 analyzed endometrial carcinomas. Of the 43 analyzed tumors, 18
      (41.8%) were in the high score (8-12) category with a strong OPN expression
      level; 11 of 43 (25.5%) showed a moderate score (4-7) category. In endometrioid
      carcinoma with increasing malignancy grade, increasing areas with low OPN
      expression level or complete loss of OPN expression could be observed. In
      contrast, serous tumors showed a strong OPN expression level. Similar results
      could be found in Western blot analysis. CEACAM1 showed similar results and could
      be found to be coexpressed with OPN in normal human endometrium and in
      endometrial neoplasia as we showed using immunofluorescence. In this study, the
      different expression patterns of OPN in endometrial tumors could additionally
      support the biological diversity of endometrioid and serous carcinomas together
      with other markers. We suggest that OPN might play a different role in the
      pathogenesis of endometrial cancer (possibly as a functional complex with
      CEACAM1) and could be relevant for invasive growth of such lesions.

PMID- 16633067
TI  - Endometrial polyp with sex cord-like pattern.
AB  - We report on an unusual endometrial polyp in a postmenopausal woman taking
      tamoxifen for 7 years after surgical resection of a breast carcinoma. A 63-year
      old woman with endometrial thickening was submitted to hysteroscopy with biopsy,
      which revealed a polyp with a sex cord-like pattern. The hysterectomy specimen
      showed florid adenomyosis, and in the background, there were rare sex cord-like
      foci. Immunohistochemistry can be useful in differentiating sex cord-like
      elements from metastatic breast cancer to endometrium. This is, to our knowledge,
      the first observation in literature correlated to tamoxifen intake.

PMID- 16633068
TI  - Myxoid leiomyosarcoma of the uterus in a patient receiving tamoxifen therapy: a
      case report.
AB  - In this paper, we present a case of myxoid leiomyosarcoma development in a
      patient receiving tamoxifen for 3 years because of breast cancer. The myxoid
      leiomyosarcoma should be included in the differential diagnosis of any uterine
      tumor with a predominantly myxomatous composition. A review of the literature
      indicates that tamoxifen may increase not only the risk for endometrial cancer
      but also for uterine sarcoma, suggesting vigilance for uterine cancer in women
      who are being treated with this drug.

PMID- 16633069
TI  - Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.
AB  - There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and
      differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to
      carcinoma and, traditionally, is not graded. There are currently 3 grading
      systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade
      system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial
      lesions, and the revised International Society for the Study of Vulvovaginal
      Disease (ISSVD) classification which has no grading of VIN. According to the
      ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category,
      simply termed warty-basaloid VIN. To determine the best system for grading warty
      basaloid VIN and learn more about differentiated VIN, we reviewed the pathology
      of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN,
      29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4
      had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1
      occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree
      of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases
      (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and
      because VIN 2 and 3 were difficult to distinguish and there appears little
      clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be
      abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness
      of vulvar conditions, so that differentiated VIN is biopsied before cancer has
      supervened.

PMID- 16633070
TI  - p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas
      of the uterine cervix.
AB  - Small cell carcinomas (SmCCs) of the uterine cervix are rare tumors. The
      knowledge regarding protein expression of several checkpoint candidates of cell
      cycle regulation is limited. Surgically treated SmCCs were selected from our
      files for immunohistochemical staining (neuroendocrine markers, p53, p16, p14,
      and cyclin D1). Polymerase chain reaction analysis, using general primers, was
      performed for human papillomavirus analysis. Nine of 677 tumors (1.3%) were
      classified as SmCCs after Grimelius staining (8/9 tumors positive) and
      immunohistochemical reaction against neurone-specific enolase, chromogranin A,
      synaptophysin (7/9 positive tumors), and CD 56 (8/9 positive tumors). All
      specimens were positive for at least two of the above. Two SmCCs were p53
      positive and one case was p14 positive. Cyclin D1 staining was completely
      negative. All cases showed strong nuclear and/or cytoplasmic p16-immunostaining.
      Seven tumors represented human papillomavirus positivity for high-risk types.
      Four patients died of the tumor after a median time of 36.7 months (range, 15-56
      months), representing a 5-year survival rate of 56%. The results suggest that p16
      is up-regulated or accumulated in the SmCCs of the uterine cervix, probably
      caused by infection with human papillomavirus. p14 inactivation is of high
      prevalence in SmCCs and detection rate of p53 is similar to other histologic
      types of cervical carcinomas.

PMID- 16633071
TI  - p16INK4a overexpression independent of human papillomavirus infection in lobular
      endocervical glandular hyperplasia.
AB  - A high rate of human papillomavirus (HPV) infection has been reported in cervical
      cancer and precancerous lesions. Many studies also have shown that p16INK4a
      overexpression is of diagnostic value for high-risk HPV-related cervical cancer
      and precursors. Lobular endocervical glandular hyperplasia (LEGH) is a rare
      lesion of the uterine cervix. There is one report about HPV infection and few
      studies on p16INK4a expression in LEGH. Therefore, we 1) detected HPV infection
      and examined p16INK4a expression and 2) observed the relationship between HPV and
      p16INK4a overexpression in LEGH. The immunohistochemical expression of p16INK4a
      was studied in 24 cases of LEGH. HPV DNA was also evaluated in these cases using
      a polymerase chain reaction technique. Strong (++) p16INK4a immunoreactivity was
      observed in 10 (41.7%) of the 24 LEGH cases; a moderate (+) pattern was observed
      in 9 (37.5%) cases; a weak (+) pattern was observed in 2 (8.3%) cases; and the
      remaining 3 (12.5%) cases showed negative expression. Overall, p16INK4a
      overexpression was seen in 87.5% of the cases (21/24). HPV DNA was not detected
      in any of the 24 LEGH cases. These results suggest that p16INK4a overexpression
      is independent of HPV infection in LEGH.

PMID- 16633072
TI  - History of gynecological pathology XIX. Walther Schauenstein: an early austrian
      pioneer of cervical pathology with comments on his successors.

PMID- 16633073
TI  - Effects of rat sinoaortic denervation on the vagal responsiveness and expression
      of muscarinic acetylcholine receptors.
AB  - We studied heart rate (HR) responses to vagal electrical stimulation (VES) and
      the expression of muscarinic acetylcholine receptors (mAChRs) in the rat atria 1
      day (SADa) and 20 days (SADc) after sinoaortic denervation (SAD). Arterial blood
      pressure (BP) was recorded in conscious, unrestrained rats and during vagal
      electrical stimulation of the vagus nerve. In the acute phase, SADa rats had
      hypertension, tachycardia, and increased blood pressure lability. In the chronic
      phase, heart rate and blood pressure in SADc rats returned to normal whereas
      blood pressure lability remained increased. VES produced a frequency-dependent
      bradycardia that was higher in SADa and SADc groups. Binding experiments with [H]
      N-methylscopolamine showed that in the chronic phase of SAD mAChRs density (SADc
      = 412.2 +/- 28.64, SADa = 273.38 +/- 48.37 and CTR = 241.5 +/- 25.35 fmol/mg of
      protein, P < 0.05) and affinity increased in SADc rats (reduced dissociation
      constant: SADc = 0.45 +/- 0.05, SADa = 1.01+/-0.26, and CTR = 0.98 +/- 0.12 mM, P
      < 0.05). Our study provides evidence that vagal hyperresponsiveness coexists with
      increased sympathetic activity in SADa rats without a concomitant increase in
      mAChRs density or affinity, suggesting that complex mechanisms might modulate the
      "accentuated antagonism" observed in the acute SAD phase. However, SADc rats had
      increased bradycardia to VES, increased affinity, and upregulation of mAChRs in
      the atria. Our results show that, 20 days after SAD in the rat, functional and
      cellular adaptations occur in the cardiac parasympathetic efferent pathway that
      may contribute to other regulatory mechanisms to compensate for cardiovascular
      changes provoked by baroreceptor arch disruption.

PMID- 16633074
TI  - Cardiovascular and electrocardiographic effects of the dopamine receptor agonists
      ropinirole, apomorphine, and PNU-142774E in conscious beagle dogs.
AB  - To confirm recent in vitro findings, we examined the cardiovascular and
      electrocardiographic (ECG) effects of the dopamine receptor agonists ropinirole,
      apomorphine, and PNU-142774E in conscious dogs. Intravenous (i.v.) infusions of
      ropinirole totaling 20 microg/kg maximally reduced mean arterial pressure (MAP; 
      16 mm Hg) and the ECG PR interval (-13 milliseconds) and increased heart rate
      (HR; +29 b/min) and QTc length (+33 ms) at a peak plasma drug concentration
      (p[drug]) of 3.5 ng/ml. I.V. PNU-142774E was better tolerated through 66
      microg/kg and a maximal p[drug] of 5.9 ng/ml with negligible cardiovascular
      changes and mild QTc reduction (13 ms). Apomorphine (25 microg/kg i.v.) was
      intermediate to ropinirole and PNU-142774E for emesis and peak changes in MAP (-6
      mm Hg), HR (+24 b/min), and QTc (+15 milliseconds) at a mean p[drug] of 3.4
      ng/ml. By comparison, the class III antiarrhythmic trecetilide (2.0 mg/kg bolus)
      increased QTc (+58 ms) without affecting mean arterial pressure or heart rate.
      This study establishes that in conscious dogs, the selective dopamine receptor
      agonist PNU-142774E has fewer cardiovascular and emetic effects than ropinirole
      and apomorphine and supports prior in vitro findings that ropinirole and
      apomorphine but not the PNU-142774E imidazoquinolin analog sumanirole reduces the
      delayed rectifier current in HERG transfected cells.

PMID- 16633075
TI  - Nicotine effect on cardiovascular system and ion channels.
AB  - Smoking is a leading cause of cardiovascular disease, hypertension, myocardial
      infarction, and stroke. Nicotine is one of the components of cigarette smoke.
      Nicotine effects on the cardiovascular system reflect the activity of the
      nicotine receptors centrally and on peripheral autonomic ganglia. It has been
      found that cigarette smoke extract-induced contraction of porcine coronary
      arteries is related to superoxide anion-mediated degradation of nitric oxide.
      Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated
      cigarette smoke impairment of arterial relaxation. Treatment of smokers with
      vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of
      large peripheral arteries. Thus it appears that chronic smoking and acute
      exposure to cigarette smoke extract may alter endothelium-dependent reactivity
      via the production of oxygen derived free radicals. This review discusses the
      effects of nicotine on resistance arterioles, compliance arteries, smooth muscle
      cells, and ion channels in the cardiovascular system. We discuss studies
      performed on humans, nicotine-exposed animals, and cell cultures yielding varying
      and inconsistent results that may be due to differences in experimental design,
      species, and the dose of exposure. Nicotine exposure appears to induce a
      combination of free radical production, vascular wall adhesion, and a reduction
      of fibrinolytic activity in the plasma.

PMID- 16633076
TI  - Effects of low-dose quinidine on ventricular tachyarrhythmias in patients with
      Brugada syndrome: low-dose quinidine therapy as an adjunctive treatment.
AB  - Quinidine is suggested as an effective agent to suppress ventricular fibrillation
      (VF) in the Brugada syndrome by inhibiting transient outward K(+) current (Ito)
      leading to the reduction and abbreviation of the disparity of repolarization in
      the right ventricular outflow region and ST segment elevation in the right
      precordial leads of electrocardiogram. We sought to assess the efficacy of low
      dose (300-600 mg) quinidine sulfate on the prevention of ventricular fibrillation
      induction by programmed electrical stimulation (PES) and spontaneous ventricular
      fibrillation episodes during the subsequent follow-up period. Electrophysiologic
      study was performed in 14 patients with the Brugada syndrome (14 men, mean age 50
      +/- 11 years, range 32-75) before and during the treatment with low-dose
      quinidine and evaluated the efficacy of the drug therapy. Ventricular
      fibrillation was induced in all the patients by programmed electrical stimulation
      at baseline. After oral quinidine administration (300 mg or 600 mg/d), programmed
      electrical stimulation was repeated. Ventricular fibrillation induction was
      prevented in 6 of 14 patients (44%). Serum quinidine concentration was higher in
      the patients with suppressed VF induction than those without (1.88 +/- 0.44
      versus 1.31 +/- 0.43 microg/ml, respectively). After programmed electrical
      stimulation, 9 of 14 patients (64%), in whom four had implantable cardioverter
      defibrillator implantation, continued to receive quinidine. During a mean follow
      up period of 31 months on quinidine, no side effects except one with diarrhea
      were observed (12.5%). There were no ventricular fibrillation recurrences in 3 of
      the 9 patients, who had frequent implantable cardioverter defibrillator
      discharges due to ventricular fibrillation attacks before treatment with
      quinidine. Low-dose quinidine has a potential as an adjunctive therapy for
      patients of the Brugada syndrome with frequent implantable cardioverter
      defibrillator discharges.

PMID- 16633077
TI  - Role of cGMP in sildenafil-induced activation of endothelial Ca2+-activated K+
      channels.
AB  - Intracellular cGMP is an important second messenger in endothelial cells. Because
      Ca(2+)-activated K(+) channels with large conductance (BK(Ca)) have been shown to
      regulate endothelial cell functions, the aim of the present study was to examine
      whether sildenafil modulates BK(Ca) activity in cultured human endothelial cells.
      Changes of the endothelial cell membrane potential were analyzed using the
      fluorescence dye DiBAC. The patch-clamp technique was used to study BK(Ca) in
      human endothelial cells of umbilical cord veins (HUVEC). Intracellular Ca(2+)
      levels were analyzed using Fura-2 fluorescence imaging. Sildenafil caused a dose
      dependent (0.05-5 micromol/l) hyperpolarization of the endothelial cells with a
      maximum at a concentration of 1 micromol/l. A significant increase of BK(Ca)
      activity was induced by sildenafil (1 micromol/l) perfusion. BK(Ca) open state
      probability (NPo) was also increased by the cGMP-analogue 8-bromo-cGMP (0.5
      mmol/l), whereas inhibition of the cGMP-dependent kinase (PKG) had no effect on
      NPo. PKG-inhibition abolished 8-bromo-cGMP induced BK(Ca) activation, and reduced
      sildenafil induced NPo. Furthermore, sildenafil caused a significant increase of
      intracellular calcium that was blocked by the BK(Ca) inhibitor iberiotoxin (100
      nmol/l). In conclusion sildenafil activates BK(Ca) by a mechanism, which involves
      cGMP. The activation of the BK(Ca) is responsible for the sildenafil-induced
      increase of intracellular Ca(2+).

PMID- 16633078
TI  - Impairment on cardiac output and blood flow adjustments to exercise in L-NAME
      induced hypertensive rats.
AB  - The objective of the present study was to investigate cardiovascular adjustments
      at rest, during exercise, and 1 hour after exercise among nitric oxide (NO)
      blockade-induced hypertensive rats. Male Wistar rats (308 +/- 9 g) assigned as
      normotensive (n = 9) and hypertensive (N(omega)-nitro-L-arginine methyl ester, n
      = 11) underwent a bout of exercise. Arterial pressure (AP) and blood oxygen
      saturation were measured. Colored microspheres were used to evaluate blood flow
      and cardiac output (CO). Hypertensive rats (143 +/- 5 vs. 102 +/- 4 mmHg in
      normotensive rats), who presented reduced CO (57 +/- 6 vs. 102 +/- 7 mL/min in
      normotensive), also presented diminished blood flow in kidney, lung, and muscles
      at rest in comparison with normotensive rats. Exercise increased AP (20%), heart
      rate (40%), and CO (32%) among the normotensive rats, whereas the hypertensive
      rats presented an increased heart rate (40%) accompanied by a reduced venous
      oxygen saturation (45.5 +/- 2.1% vs. 75 +/- 0.7% in normotensive rats). Muscle
      vasodilatation, which was observed among the normotensive rats and is considered
      a hallmark adjustment to exercise, was not observed among the hypertensive rats.
      After a 1-hour interval from exercise most of the evaluated parameters returned
      to basal values. In conclusion, exercise did not cause an increase in CO, AP, or
      blood flow to skeletal muscle in hypertensive rats. However, it was associated
      with a significant increase in the arterio-venous oxygen content difference in NO
      blocked rats, thus suggesting that hypertension associated with impairment in NO
      release induced different cardiovascular adjustments to exercise.

PMID- 16633079
TI  - The platelet inhibitory effects and pharmacokinetics of prasugrel after
      administration of loading and maintenance doses in healthy subjects.
AB  - Prasugrel (CS-747, LY640315), a novel thienopyridine, is a potent and orally
      active antiplatelet agent in vivo. The aims of this double-blind, double-dummy,
      placebo-controlled, randomized, parallel group phase 1 study were to investigate
      the antiplatelet effects of prasugrel after oral administration of a loading dose
      (LD) and subsequent 20 days of once-daily maintenance dosing (MD), to
      characterize the pharmacokinetics of prasugrel metabolites with an LD/MD regimen,
      and to assess the safety and tolerability of prasugrel in healthy subjects.
      Subjects were randomly assigned in a 1:1:1 ratio to prasugrel 40 mg LD/7.5 mg MD
      (n = 11), prasugrel 60 mg LD/15 mg MD (n = 10), or placebo LD/placebo MD (n =
      11). Prasugrel 40 and 60 mg LDs provided rapid and consistent inhibition of 20
      microM adenosine diphosphate (ADP)-stimulated platelet aggregation. Prasugrel 7.5
      and 15 mg MDs maintained inhibition in a dose-dependent manner. The
      pharmacokinetic data indicate that exposure to prasugrel metabolites occurs
      rapidly after dosing and is consistent with dose proportionality. Within the
      limitations of this study, the safety and tolerability results suggest that
      prasugrel is well tolerated when dosed as an initial LD followed by a lower daily
      MD for 20 days. Prasugrel LDs and MDs provide rapid and sustained inhibition of
      ADP-mediated platelet aggregation.

PMID- 16633080
TI  - Enhanced endothelium-dependent vasodilatation by dual endothelin receptor
      blockade in individuals with insulin resistance.
AB  - Insulin resistance is associated with endothelial dysfunction and increased
      production of the pro-inflammatory vasoconstrictor peptide endothelin-1 (ET-1).
      The aim of this study was to test the hypothesis that blockade of ET receptors
      results in enhanced endothelium-dependent vasodilatation (EDV) in individuals
      with insulin resistance. Twelve individuals with insulin resistance without any
      history of diabetes or cardiovascular disease and 8 age-matched controls with
      high insulin sensitivity, as determined by hyperinsulinemic-euglycemic clamp,
      were investigated on 2 separate occasions using forearm venous occlusion
      plethysmography. Endothelium-dependent and endothelium-independent vasodilatation
      was determined before and after selective ET(A) and dual ET(A)/ET(B) receptor
      blockade. A 60 minute intraarterial infusion of the ET(A) receptor antagonist
      BQ123 (10 nmol/min) combined with the ET(B) receptor antagonist BQ788 (5
      nmol/min) evoked a significant increase in acetylcholine-mediated EDV (P < 0.01)
      in individuals with insulin resistance. The endothelium-independent vasodilator
      response to nitroprusside was not changed by dual ET(A)/ET(B) receptor blockade.
      Dual ET(A)/ET(B) receptor blockade did not affect the response to acetylcholine
      or nitroprusside in the insulin-sensitive group. Selective ET(A) receptor
      blockade did not evoke any changes in endothelium-dependent or endothelium
      independent vasodilatation in either group. This study demonstrates that dual
      ET(A)/ET(B) receptor blockade, but not selective ET(A) blockade, enhances EDV in
      subjects with insulin resistance, suggesting that ET-1 is involved in the
      regulation of endothelial function in individuals with insulin resistance.

PMID- 16633081
TI  - Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and
      cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats.
AB  - This study evaluated the effects of BAY 41-2272 (BAY), a specific activator of
      sGC NO-independent action on changes of mean arterial blood pressure, heart and
      left ventricle weight indexes, cardiomyocyte hypertrophy (Vv) and fibrosis area
      induced by chronic N-nitro-L-arginine methyl ester (L-NAME) treatment in rats.
      The animals were divided into (a) control group, (b) L-NAME group, (c) L-NAME+BAY
      group, and (d) BAY group. Eight weeks of L-NAME treatment caused a significant
      increase in mean arterial blood pressure when compared with untreated rats (173
      +/- 11.1 and 109 +/- 5.0 mm Hg, respectively; P < 0.01). L-NAME + BAY cotreatment
      abolished the L-NAME-induced hypertension (112 +/- 5.1 mm Hg; P < 0.01).
      Significant increases in heart and left ventricle weight indexes and in Vv were
      observed in the L-NAME-treated animals compared with control group, and
      concomitant treatment with BAY significantly attenuated this hypertrophic effect.
      Treatment with L-NAME presented several areas of repairing fibrosis in left
      ventricles, and this effect was also abolished by BAY cotreatment. Our results
      demonstrate that BAY 41-2272 inhibits hypertension and prevents heart
      abnormalities (cardiac hypertrophy and increased fibrosis areas) induced by NO
      synthase inhibition.

PMID- 16633082
TI  - Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without
      affecting blood pressure in DOCA-salt hypertensive rats.
AB  - The pleiotropic effects of statins represent potential mechanisms for the
      treatment of end-organ damage in hypertension. This study has investigated the
      effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt
      hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized
      (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1%
      NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed
      hypertension, cardiovascular hypertrophy, inflammation with perivascular and
      interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of
      ventricular action potential duration at 28 days. Rosuvastatin-treated rats
      received 20 mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days
      commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received
      vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular
      hypertrophy, inflammation, fibrosis, and ventricular action potential
      prolongation, but did not modify hypertension or vascular dysfunction. We
      conclude that the pleiotropic effects of rosuvastatin include attenuation of
      aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in
      rats without altering systolic blood pressure.

PMID- 16633083
TI  - Glutathione reverses peroxynitrite-mediated deleterious effects of nitroglycerin
      on ischemic rat hearts.
AB  - This study examined the potential deleterious effect of high-dose nitroglycerin
      (NTG) on cardiac function and cellular injury after ischemia (30 min) and
      reperfusion (120 min) in isolated perfused rat hearts. Low-dose (0.75 microg/h),
      medium-dose (3.75 microg/h), high-dose (15 microg/h) NTG or high-dose NTG plus
      glutathione (GSH, 1 mmol/L) was administrated at the time of reperfusion.
      Administration of high-dose NTG significantly exacerbated cardiac reperfusion
      injury as evidenced by increased creatine kinase and lactate dehydrogenase
      activity in coronary effluent, increased cardiomyocyte apoptosis and necrosis,
      and decreased cardiac function recovery after reperfusion. Compared with the
      vehicle group, formation of nitrotyrosine, a footprint for peroxynitrite (ONOO)
      production, was markedly increased in the hearts treated with medium-dose or high
      dose NTG. Most interestingly, cotreatment with GSH blocked high-dose NTG-induced
      ONOO formation and attenuated myocardial ischemia/reperfusion injury. Taken
      together, our present results demonstrated that administration of high-dose NTG
      aggravated, rather than attenuated myocardial ischemia/reperfusion injury likely
      via increasing ONOO formation. Coadministration of GSH may reverse the advert
      action of high-dose NTG.

PMID- 16633084
TI  - Possible involvement of calpain activation in pathogenesis of chronic heart
      failure after acute myocardial infarction.
AB  - Changes in proteolytic activity of the myocardium during the development of heart
      failure after left coronary artery ligation (CAL) of rats were examined.
      Hemodynamics of the rats at the eighth week (8w-CAL rat), but not at the second
      week (2w-CAL rat), after CAL showed the symptoms of chronic heart failure.
      Contents of mu-calpin and m-calpain, but not an intrinsic calpain inhibitor
      calpastatin, in the viable left ventricular muscle (viable LV) and the right
      ventricular muscle (RV) of the 2w-CAL and 8w-CAL rats were increased, which was
      associated with an elevation of intrinsic activities of leupeptin-sensitive,
      Ca(2+)-activated proteolysis in the cytosolic fractions of the viable LV and RV.
      Oral administration of 3 mg/kg/d trandolapril or 1 mg/kg/d candesartan from the
      second to eighth week after CAL improved the hemodynamics of 8w-CAL rats. The
      drug treatment attenuated the increases in mu-calpain and m-calpain contents and
      the elevation of the proteolytic activity of the viable LV and RV in the 8w-CAL
      rat. The drug treatment increased calpastatin content of the RV in the 8w-CAL
      rat. These results suggest that sustained activation of calpain is involved in
      the development of chronic heart failure and that trandolapril and candesartan
      prevent the activation of calpains after CAL.

PMID- 16633085
TI  - Distinct agonist responsibilities of the first and second branches of mouse
      mesenteric artery.
AB  - The mesenteric artery (MA) is suitable for consideration as a typical micro
      resistant artery for examination of arteriosclerosis. The MA is comprised of the
      first (MA1), second (MA2), and additional fine structural branches; however,
      differences in terms of responsibilities of these branches have not been
      assessed. The objective of this study was to differentiate contractile responses
      in the MAs of mice. MA2 rings (100 microm diameter, 1 mm length) displayed
      maximal force development (846.8 +/- 55.6 microN; n = 5) upon stimulation with 50
      mM KCl under 400 microN resting tension. However, both MA1 and aorta required
      resting tension exceeding 600 microN. Treatment of MA2 with phenylephrine (PE; 10
      microM), norepinephrine (NE; 10 microM), thromboxane A(2) (analog U46619; 100
      nM), or prostaglandin F(2a) (PG; 10 microM) induced sustained contractions.
      Responses were 1507.8 +/- 88.8, 1543 + 5 +/- 149.6, 2088.6 +/- 151.6, and 1441.9
      +/- 103.6 microN (n = 7), respectively. These values were markedly larger than
      those of the KCl-induced response. In MA1 and aorta, PE-induced and NE-induced
      responses were indistinct from the KCl response. This investigation revealed that
      MA1 exhibits responsibilities similar to those of the aorta, whereas MA2
      possesses distinct responsibilities. MA2 might serve as a micro-resistant artery
      model.

PMID- 16633086
TI  - Short-term atorvastatin treatment does not modify neointimal morphology but
      reduces MMP-2 expression in normocholesterolemic rabbit stented arteries.
AB  - The aim of our study was to explore some potential pleiotropic effects of
      atorvastatin, after stenting in the iliac arteries of normocholesterolemic
      rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized
      into either the control group (standard chow, CTRL, n = 15) or the atorvastatin
      group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were
      harvested for histomorphometry and neointimal analysis [macrophages, matrix
      metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular
      smooth muscle cells, and collagen]. Atorvastatin did not induce significant
      histomorphometric and inflammatory modifications but reduced neointimal
      expression of MMP-2 with no modification of tissue inhibitor of metalloproteinase
      2, and also induced higher neointimal collagen content (Ator vs. CTRL: MMP-2:
      0.05 +/- 0.03 vs. 0.70 +/- 0.20, P < 0.01; collagen: 17.0+/-0.7%/mm vs. 12.0 +/-
      1.2%/mm(2) P < 0.01). Atorvastatin treatment also induced a significant decrease
      in neointimal vascular smooth muscle cells and cellular density (respectively:
      2.0 +/- 0.2 vs. 1.4 +/- 0.2, P < 0.05; 5406 +/- 241 nuclei/mm(2) vs. 4402 +/- 163
      nuclei/mm(2), P < 0.001). Our study provides new insights into the field of MMP
      response to stenting and the effects of statin therapy, which could have
      important implications in the field of in-stent restenosis.

PMID- 16633087
TI  - Effect of resveratrol on nitrate tolerance in isolated human internal mammary
      artery.
AB  - The present study aims to examine whether resveratrol, a natural antioxidant
      present in red wine, restores the tolerance to nitroglycerin (GTN) on isolated
      human internal mammary artery (IMA), using an in vitro model of nitrate
      tolerance. IMA rings were obtained from 53 male patients undergoing coronary
      bypass operation. Nitrate tolerance was induced by incubating the artery ring
      with 100 microM GTN for 90 minutes. Concentration-response curves to GTN (10(-9)
      to 10(-4) M) were obtained on IMA rings precontracted with noradrenaline. A low
      concentration (5 microM) of lucigenin was used as a tool to measure superoxide
      production in IMA segments. GTN produced concentration-dependent relaxation in
      isolated human IMA rings. Preexposure of artery rings to GTN reduced the
      relaxations to GTN [E(max) values: 105 +/- 2% and 76 +/- 3%, n = 10 to 12, P <
      0.05; EC(50) values (-log M): 6.72 +/- 0.05 and 4.95 +/- 0.06, P < 0.05,
      respectively]. Relaxation to sodium nitroprusside remained unchanged. Diminished
      relaxation to GTN is partially restored after removing endothelium or L(G)-nitro
      L-arginine (L-NOARG, 10 M) or superoxide dismutase (20 and 200 U/mL) or catalase
      (200 U/mL) pretreatments. Pretreatments with resveratrol (1, 10, and 20 microM)
      for 20 minutes relatively improved the reduced relaxation to GTN in tolerant IMA
      rings. Coadministration of L-NOARG with resveratrol did not abolish the
      beneficial effect of resveratrol on nitrate tolerance. The inhibitory effect of
      resveratrol on GTN-induced tolerance was not abolished in arterial rings without
      endothelium. Exposure to GTN increased superoxide production in IMA segments with
      endothelium. Endothelium denudation, L-NOARG, or superoxide dismutase
      pretreatments markedly inhibited the increased superoxide production in tolerant
      arteries. Resveratrol (1 and 10 microM) almost completely abolished basal or
      NAD(P)H-stimulated superoxide production in tolerant and nontolerant arteries.
      Vascular tolerance to GTN, in in vitro tolerant human IMA rings, can be induced
      by endothelial superoxide anions. Resveratrol partially restored the reduced
      relaxation to GTN by inhibiting NAD(P)-derived superoxide production in
      endothelium.

PMID- 16633088
TI  - Comparison of the effect of diuretics on carotid blood flow in stroke patients.
AB  - OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used
      in the management of blood pressure after stroke. There are theoretical reasons
      why these agents may differ with regard to their cardiovascular effects. We
      compared the effect of these agents on blood pressure and cerebral blood flow in
      a group of stroke patients. METHODS: In a prospective, randomized, double-blinded
      study we investigated the effect of 28 days' treatment with BDZ 2.5 mg od or IND
      2.5 mg od on blood pressure and cerebral blood flow in a group patients with
      recent first-ever ischemic stroke. Using extracranial carotid and transcranial
      ultrasound we assessed carotid blood flow and intracranial hemodynamics. RESULTS:
      All data are expressed as mean (SD). Twenty-five patients completed the protocol
      (age 68.8 +/- 10.6 y). Groups I (IND) and B (BDZ) comprised 13 and 12 patients,
      respectively. Groups were well matched for demography and baseline
      characteristics. Percent change in mean arterial pressure reduction from baseline
      was (I = -14.7 +/- 12.5, P < 0.001 vs. B = -7.7 +/- 9.16 mm Hg, P = 0.02). There
      was a trend toward increased carotid blood flow in both groups (I = +10% +/- 47,
      P = 0.4 vs. B = +33% +/- 47, P = 0.12). No significant change in middle cerebral
      artery mean flow velocity or pulsatility index was observed. There was no
      significant difference between the 2 drugs with regard to change in blood
      pressure (95% confidence interval for difference -2.5 to 16.3 mm Hg, P = 0.14) or
      carotid blood flow (95% confidence interval for difference -58 to 27 mL/s, P =
      0.45). CONCLUSIONS: Both diuretics reduced blood pressure to a similar and
      significant degree. There was no evidence of an adverse effect on cerebral blood
      flow or intracranial hemodynamics induced by either agent. No significant
      difference between the effect of IND and BDZ was observed.

PMID- 16633089
TI  - Akrinor-induced relaxation of pig coronary artery in vitro is transformed into
      alpha1-adrenoreceptor-mediated contraction by pretreatment with propranolol.
AB  - Akrinor (AKR), a mixture of theodrenaline (TDR) and cafedrine (CDR), is a
      sympathomimetic agent used to counter transitory hypotension. Although some cases
      of vascular complications associated with AKR have been reported there are no
      experimental data about its direct effects on coronary arteries. The effects of
      AKR, TDR, CDR, and ephedrine (EDR) were studied on the isometric contraction of
      the ring preparations of pig coronary arteries precontracted with KCl. The
      influence of endothelium removal and preincubation with nonselective beta
      adrenoreceptor antagonist propranolol (PROP), alpha(1)-adrenoreceptor antagonist
      prazosin, dopamine receptor antagonist SCH 23390, and adenosine receptor
      antagonist CGS 15943 were also tested. AKR, TDR, and CDR produced relaxation of
      the preparations. Preparations without endothelium were more sensitive to AKR
      relaxing effects. EDR produced an increase of vascular ring tonus. AKR, TDR, and
      EDR produced contraction in preparations pretreated with PROP. Higher
      concentrations of AKR relaxed PROP-pretreated preparations. AKR-induced
      contraction could be prevented by pretreatment with prazosin. Dopamine and
      adenosine receptor antagonists did not influence relaxing effects of AKR. In
      conclusion, AKR and its constituents induce the relaxation of pig coronary artery
      preparations precontracted with KCl. The observed contraction in the preparations
      pretreated with PROP was probably due to stimulation of unmasked alpha(1)
      adrenoreceptors.

PMID- 16633090
TI  - Endothelin ETA receptor blockade with darusentan increases sodium and potassium
      excretion in aging rats.
AB  - This study investigated whether intrarenal endothelin-1(ET-1) contributes to
      sodium excretion in aged rats. Metabolic function studies were performed in male
      Wistar rats (3 and 24 months) treated with placebo or the orally active ET(A)
      receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure
      was measured using an intra-arterial catheter. Electrolytes, aldosterone levels,
      renin activity, and angiotensin converting enzyme activity were determined in
      plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na(+), K(+)
      ATPase subunits was measured in the renal cortex and medulla. Aging was
      associated with a marked decrease in urinary excretion of sodium, chloride, and
      potassium (all P < 0.001) as well as renin activity (P < 0.05), but had no
      significant effect on gene expression of ENaC or Na(+), K(+)-ATPase subunits. In
      aged rats, darusentan treatment increased ion excretion (P < 0.05), reduced
      cortical gene expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase (both P <
      0.05), and increased plasma aldosterone levels (P < 0.01). These data demonstrate
      a decrease of sodium and potassium excretion in aged rats, changes that are
      partly sensitive to ETA receptor blockade. Treatment with darusentan also reduced
      cortical expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase and increased
      plasma aldosterone levels independently of blood pressure, electrolytes, renin
      activity, or angiotensin converting enzyme activity. These findings may provide
      new pathogenetic links between aging and sodium sensitivity.

PMID- 16633091
TI  - Inhibitory effect of Magnolia officinalis and lovastatin on aortic oxidative
      stress and apoptosis in hyperlipidemic rabbits.
AB  - Oxidative stress and apoptosis are 2 major characteristics of the progression of
      atherosclerosis. Both lovastatin and Magnolia officinalis are hypocholesterolemic
      agents. Therefore, we investigated the effect of M. officinalis extract on the
      prevention of atherosclerosis in comparison with lovastatin. Twenty
      hyperlipidemic rabbits were served one of the following diets: a high-fat and
      cholesterol diet (cholesterol group, 10% corn oil and 0.5% cholesterol), a high
      fat and cholesterol diet supplemented with M. officinalis extract (300 mg/kg) or
      lovastatin (6 mg/kg). The plasma lipids, oxidative stress (measured by free
      radical, malondialdehyde, and oxidative DNA damage), and arterial lesions
      significantly decreased in the M. officinalis and lovastatin groups when compared
      with the cholesterol group. Moreover, the expressions of Fas ligand, caspase 8,
      and caspase 9 in the aortic arches were also markedly lowered after M.
      officinalis and lovastatin supplements. Therefore, the results indicate that the
      antiatherogenic effect of M. officinalis is involved with a suppression of
      oxidative stress and with the down-regulation of apoptosis-related gene
      expression in hyperlipidemic rabbits.

PMID- 16633092
TI  - Metabolic syndrome, new onset diabetes, and new end points in cardiovascular
      trials.
AB  - Metabolic syndrome affects approximately 44% of the US population over the age of
      50 years. Although conflicting definitions exist, the syndrome is typically
      characterized by abdominal obesity, dyslipidemia, hypertension, and insulin
      resistance. Thus, it is a major risk factor for both coronary heart disease and
      type 2 diabetes. Furthermore, the risk of cardiovascular (CV) death is
      significantly increased in patients with diabetes and/or the metabolic syndrome.
      Although very few studies exist in patients with the metabolic syndrome,
      lifestyle changes and drug intervention targeted at the individual components
      have been shown to reduce the risk of developing diabetes and the incidence of CV
      disease in high-risk patients. Because many of the conventional antihypertensive
      drugs may affect the development of new onset diabetes, both positively and
      negatively, the choice of therapy is particularly important in this population.
      However, the long-term clinical trials to date have either not included new onset
      diabetes as a protocol end point or used various different criteria, making
      comparisons difficult. This review assesses the need for future research into
      metabolic syndrome and discusses whether clinical surrogates for CV end points,
      such as new onset diabetes, should be included in clinical trials of new drugs,
      new regimens, or new indications.

PMID- 16633093
TI  - Difference in the characteristics of ETA-receptor-stimulated response between rat
      small pulmonary and renal arteries.
AB  - We investigated the difference in the characteristics of endothelin-1 (ET-1)
      induced contraction and the responses of intracellular Ca(2+) concentration
      ([Ca(2+)](i)) between rat small pulmonary artery and renal artery. ET-1 (30 nM)
      failed to elicit any contraction in renal arteries pretreated with 3 microM BQ
      123, an ETA blocker. However, in the pulmonary artery a combination of BQ-123 and
      BQ-788, an ETB blocker (5 microM each), only partially inhibited the ET-1-induced
      contraction (by 25%). To focus on the ETA receptor, in the presence of 5 microM
      BQ-788, nitric oxide donors (sodium nitroprusside and (+/-)-S-nitroso-N
      acetylpenicillamine) and forskolin reduced both the ET-1-induced contraction and
      increase in [Ca(2+)](i) in both pulmonary and renal arteries. However, the
      effects were stronger in the renal than in the pulmonary artery. ET-1-induced
      increase in [Ca(2+)](i) was only partially attenuated by 10 microM verapamil (to
      81% of control) in pulmonary arteries but was reduced to 56.1% of control in
      renal arteries. Our results provide evidence that ET-1 may activate ET
      receptor(s) insensitive to both BQ-123 and BQ-788 in rat small pulmonary artery,
      at least under these conditions. Furthermore, the effects of relaxants such as L
      type Ca(2+) channel blocker and nitric oxide donors on the ET-1-induced
      contraction were studied.

PMID- 16633094
TI  - Isoflurane inhaled at the onset of reperfusion potentiates the cardioprotective
      effect of ischemic postconditioning through a NO-dependent mechanism.
AB  - Postconditioning (PCD) is known to reduce infarct size (IS). Here, we
      investigated whether isoflurane, which is known to potentiate preconditioning,
      also potentiates PCD and whether NO is involved. Accordingly, open-chest rabbits
      underwent 30-minute coronary artery occlusion (CAO) followed by 3-hour coronary
      artery reperfusion (CAR). In control and postconditioned (4 cycles of 30s-CAR/30s
      CAO after the 30-min CAO), rabbits were anesthetized with pentobarbital alone or
      in combination with isoflurane inhaled (i) throughout the experiment or (ii) only
      during CAR. With pentobarbital alone, PCD significantly reduced IS versus control
      (39 +/- 7% vs. 55 +/- 4% of the risk zone, respectively, P < 0.05). Isoflurane-
      0.5% throughout the experiment did not alter IS in both control and PCD groups.
      Isoflurane--2% throughout the experiment reduced IS in control (37 +/- 8%, P <
      0.05 vs. pentobarbital alone) and enhanced the protective effect of PCD (IS = 21
      +/- 3%, P < 0.05 vs. both control and PCD under pentobarbital alone). When
      isoflurane--2% was administered only during reperfusion, IS was not changed in
      control (53 +/- 3%) but combination with PCD reduced IS to 23 +/- 4% (P < 0.05
      vs. both control and PCD under pentobarbital alone). L-arginine analog N-nitro-L
      arginine methyl ester administered before reperfusion did not properly alter IS
      (53 +/- 6%) but abolished the effect of PCD alone (IS = 47 +/- 7%) or in
      combination with isoflurane--2% during reperfusion (55 +/- 3%). Thus, isoflurane
      potentiates PCD at reperfusion through a NO-dependent mechanism.

PMID- 16633095
TI  - Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces
      myocardial infarct size without affecting hemodynamics.
AB  - Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in
      parts of Europe. We carried out the first study to determine whether a 10-day
      course of mildronate could reduce myocardial infarct size (IS) during acute
      myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate
      (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously
      for 10 days before ischemia-reperfusion. Rats were then subjected to 45 minutes
      of left coronary artery occlusion and 2 hours of reperfusion. The 2 groups had
      identical areas at risk: treated 38 +/- 3%; controls 38 +/- 2%. The amount of
      necrosis was smaller in the mildronate group at 16 +/- 2% of the left ventricle
      versus controls, 22 +/- 2% (P = 0.05); and for any amount of risk >25%, necrosis
      was smaller in the treated group (P = 0.0035). Myocardial IS (% of risk zone) was
      43+/-3% in the mildronate-treated rats, and 57+/-4% in controls (P = 0.004).
      During occlusion, there were no differences between the 2 groups in heart rate
      (216 +/- 12 bpm, mildronate and 210 +/- 9 bpm, control), in mean arterial
      pressure (60 +/- 2 mm Hg, mildronate and 64 +/- 3 mm Hg, control) or in the
      frequency of arrhythmias. Our study for the first time demonstrated that a 10-day
      treatment with mildronate reduced myocardial IS in an experimental model of acute
      myocardial ischemia, without any effect on hemodynamics.

PMID- 16633096
TI  - Bile duct brushings for the early detection of cholangiocarcinoma.

PMID- 16633097
TI  - Asymptomatic ileitis: past, present, and future.
AB  - We critically review the limited data on an emerging clinical entity,
      asymptomatic ileitis. We discuss some of the current theorized etiologies of this
      phenomenon, including subclinical Crohn's disease, nonsteroidal anti-inflammatory
      drugs, and spondylarthropathies. Finally, we discuss future areas of
      investigation that may better help identify and evaluate this increasingly common
      finding.

PMID- 16633098
TI  - The effect of mosapride on esophageal motility and bolus transit in asymptomatic
      volunteers.
AB  - GOALS: To evaluate the effect of mosapride, a selective 5-hydroxytryptamine-4
      agonist, on esophageal motility and bolus transit in asymptomatic volunteers.
      STUDY: Twenty healthy subjects participated in two experiments, 7 days apart, and
      we utilized a randomized, double-blind cross-over design with 3-day pretreatments
      of placebo or mosapride. All subjects underwent combined intraluminal impedance
      manometry. RESULTS: There was no difference in the amplitude, the duration, and
      the esophageal peristaltic patterns between the two pretreatments. The lower
      esophageal sphincter (LES) pressure and the number of transient LES relaxations
      did not change after mosapride vs. placebo. However, the rate of complete bolus
      transit in liquid swallows was higher with mosapride pretreatment (92.2%) than
      with placebo (84.6%; P < 0.01). The total bolus transit time in all liquid
      swallows showed a tendency to shorten after mosapride treatment (P = 0.06). The
      liquid bolus transit became faster after mosapride, especially in manometrically
      ineffective liquid swallows (P < 0.01). The total bolus transit time for
      manometrically normal viscous swallows decreased after pretreatment with
      mosapride (7.7 seconds; range, 6.8-9.2) in comparison with placebo (8.1 seconds;
      range, 7.1-11.1; P < 0.05). CONCLUSIONS: Mosapride increases the rate of complete
      bolus transit in the esophagus, and enhances esophageal bolus transit in
      asymptomatic volunteers.

PMID- 16633099
TI  - The effect of Helicobacter pylori eradication therapy on gastric ulcer healing
      after endoscopic mucosal resection.
AB  - BACKGROUND AND AIM: It remains unclear whether Helicobacter pylori eradication
      therapy accelerates the healing of acute gastric ulcer after endoscopic mucosal
      resection (EMR) of gastric tumor. We examined the effect of H. pylori eradication
      therapy on ulcer healing after EMR. METHODS: Twenty-six patients who underwent
      successful H. pylori eradication therapy before EMR were followed prospectively.
      Patients underwent endoscopic examination 1 or 2 months after EMR, during which
      the ulcer status and reduction rate were assessed. The effect of H. pylori
      eradication on the quality of ulcer healing was also evaluated. Six patients in
      whom eradication therapy failed and 26 patients who underwent EMR without
      eradication therapy served as control subjects. RESULTS: Endoscopically, 18 (75%)
      of 24 ulcers in the eradication group were at the healing stage 1 month after
      EMR. The ulcer reduction rates were 85.0 +/- 2.6% and 96. 9 +/- 1.1% at 1 and 2
      months after EMR, respectively. Ulcer stage and reduction rate did not differ
      significantly between the eradication group and control group. However, we
      frequently observed a better quality of ulcer healing in the eradication group
      than in the control groups (P < 0.01). CONCLUSION: H. pylori eradication therapy
      does not accelerate ulcer healing after EMR but may improve the quality of ulcer
      healing of gastric ulcer after EMR.

PMID- 16633100
TI  - Percutaneous endoscopic gastrostomy sites infected by methicillin-resistant
      Staphylococcus aureus: impact on outcome.
AB  - BACKGROUND: The impact of methicillin-resistant Staphylococcus aureus (MRSA)
      colonization of percutaneous endoscopic gastrostomy (PEG) sites on morbidity and
      mortality is uncertain. AIM: We investigated the impact of known prior MRSA
      colonization on the incidence of symptomatic PEG site wound infection and
      mortality. METHODS: Consecutive patients who had PEG tubes inserted recently at
      our hospital were identified. The presence or absence of MRSA colonization before
      PEG placement was noted. Patients were observed for wound infection, and swabs
      were taken from the site if there was clinical infection. Mortality within 30
      days of PEG placement was determined. RESULTS: A total of 83 patients underwent
      PEG placement; 23 (28%) of these patients had known MRSA colonization before PEG
      placement. Of these, 13 (57%) developed symptomatic MRSA infection of the PEG
      site. The remaining 60 patients (72%) had no known prior MRSA colonization. In
      these patients, 9 (15%) developed symptomatic MRSA infection of the PEG site. The
      overall incidence of wound infection was 37% (31) of the total undergoing PEG
      placement, of whom 71% (22) had developed MRSA infection. The mortality of those
      with symptomatic MRSA infection of the PEG site was 9% (2/22), whereas the
      mortality from non-MRSA-infected PEGs was 20% (12/61). CONCLUSION: Patients with
      prior MRSA colonization had a significantly higher risk of developing symptomatic
      MRSA infection of the PEG site. However, there was still a significant risk (15%)
      of developing MRSA infection of the PEG site for patients with no known prior
      MRSA infection. MRSA infection of the PEG site did not affect mortality.

PMID- 16633101
TI  - Effect of laparoscopic Nissen fundoplication on symptoms and gastric myoelectric
      activity in gastroesophageal reflux disease.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication is an effective treatment for
      gastroesophageal reflux disease (GERD). The aim of this study was to determine
      whether laparoscopic fundoplication alters gastric myoelectric activity. Change
      of digestive symptoms was also assessed. METHODS: Sixteen patients with GERD (2
      males, 14 females, mean age: 53 years) undergoing a laparoscopic fundoplication
      participated. Electrogastrography (EGG) was assessed before and after the subject
      ingested water until full (water load). Symptoms of upper abdominal discomfort,
      early satiety, postprandial abdominal distension, nausea, vomiting, and anorexia
      were recorded. At a 2-month postoperative follow-up, preoperative tests were
      repeated. RESULTS: The EGG was abnormal in 11 of 16 patients (69%) preoperatively
      and 6 of 16 patients (38%) postoperatively. The EGG changed from abnormal to
      normal in 5 of 16 patients (31%). The percentage of power at 3 cpm increased
      significantly during the fasting state postoperatively (29.9% vs. 21.2%, P <
      0.05). There was a significant improvement in epigastric pain (P < 0.001), early
      satiety (P < 0.01), and postprandial fullness (P < 0.001). CONCLUSIONS: Increased
      presence of normal 3 cpm activity is the predominant effect of fundoplication on
      gastric myoelectric activity. Dyspeptic symptoms are also significantly improved
      postoperatively.

PMID- 16633102
TI  - Epithelial cell proliferation of the colonic mucosa in different degrees of
      colonic diverticular disease.
AB  - GOAL: This study assesses the epithelial cell proliferation in different degrees
      of diverticular disease and compares this with two different control groups.
      BACKGROUND: Hyperproliferation of the colonic mucosa has been recently described
      in diverticular disease (DD), but it is unknown whether this finding is present
      in every degree of DD. PATIENTS AND METHODS: Thirty consecutive patients with a
      new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10 with
      symptomatic uncomplicated DD, and 10 with acute uncomplicated diverticulitis)
      were enrolled. Ten matched healthy people and 10 patients with ulcerative colitis
      (UC) (5 with UC in remission and 5 with active UC) were enrolled as control
      groups. The Ki-67 antigen index of the whole crypt and the upper third was
      separately evaluated. RESULTS: Ki-67 index of the whole crypt and the upper third
      of the crypt was significantly higher in all degrees of DD compared with the
      healthy control group. In particular, asymptomatic diverticulosis showed a
      threefold higher Ki-67 index compared with that of the healthy control group
      (5.4% and 5.6% vs. 1.6% and 1.8%, respectively, P = 0.005), and similar to that
      of UC in remission (5.4% and 5.6% vs. 5.9% and 5.8%, respectively, P = not
      significant). CONCLUSIONS: We found an upward shifting of cellular proliferation
      of the colonic mucosa in patients with different degrees of DD. In particular,
      asymptomatic diverticulosis seems to show the same risk for colonic carcinoma as
      that of UC.

PMID- 16633103
TI  - Mesalazine and/or Lactobacillus casei in preventing recurrence of symptomatic
      uncomplicated diverticular disease of the colon: a prospective, randomized, open
      label study.
AB  - GOALS: To investigate the effectiveness and safety of mesalazine, with or without
      Lactobacillus casei, in preventing recurrence of symptomatic diverticular disease
      of the colon. BACKGROUND: Both mesalazine and probiotics showed recently their
      effectiveness in obtaining remission of symptomatic uncomplicated diverticular
      disease of the colon. Consistent data are not available on the optimal therapy to
      prevent recurrence of symptomatic diverticular disease of the colon. STUDY:
      Multicenter, prospective, randomized, open-label study. Ninety consecutive
      patients (36 men, 54 women, mean age 67.5 y, range 39 to 84 y), previously
      affected by symptomatic uncomplicated diverticular disease of the colon
      (remission obtained with rifaximin 800 mg/d plus mesalazine 2.4 g/d for 10 d,
      followed by mesalazine 1.6 g/d for 8 wk), were enrolled in a 12-month follow-up.
      The following symptoms were assessed at entry and through follow-up by using a
      quantitative scale: (1) constipation, (2) diarrhea, (3) abdominal pain, (4)
      rectal bleeding, and (5) mucus with the stools. After recruitment, the patients
      were randomly assigned to one of the following 3 groups: mesalazine 1.6 g/d
      (group M), L. casei DG 16 billion/d for 15 d/mo (group L); mesalazine 1.6 g/d+L.
      casei DG 16 billion/d for 15 d/mo (group LM). RESULTS: Eighty-five patients
      completed the study (94.5%): 2 patients (2.22%, 1 of group M and 1 of group LM)
      were withdrawn from the study for protocol violation and 1 (1.11%) for hospital
      admission due to acute pulmonary disease (group L); 2 patients (2.22%) were lost
      to follow-up. Seventy-five patients (88.2%) were symptom free after the 12th
      month of treatment (overall symptomatic score: (0): 23/27 patients of group M [on
      intention to treat: 76.7% confidence interval (CI 95%: 61.5 to 91.8)], 23/29 of
      group L [on intention to treat: 76.7% (CI 95%: 61.5 to 91.8)], 29/29 of group LM
      [on intention to treat: 96% (CI 95%: 94.2 to 100)] (P < 0.05). Only 10 patients
      (11.1%) showed recurrence of symptoms (overall symptomatic score: 68).
      CONCLUSIONS: Both mesalazine and L. casei DG seem to be effective in preventing
      recurrence of symptomatic uncomplicated diverticular disease of the colon, but
      their association seems to be more promising in this field.

PMID- 16633104
TI  - The nature of inflammatory bowel disease in patients with coexistent colonic
      diverticulosis.
AB  - GOALS/BACKGROUND: Reports of segmental colitis with diverticula regard this
      entity as a local disease. Our goal was to reexamine the association of
      diverticula to colitis and question the relationship of colonic diverticulosis
      with generalized inflammatory bowel disease (IBD). STUDY: A retrospective
      database review of more than 1,600 patients matched 100 cases with IBD and
      colonic diverticulosis with a control group of 100 patients with IBD without
      diverticulosis. Patients were matched by gender, IBD diagnosis, and date of
      birth. Variables examined included disease distribution, strictures, fistulae,
      extraintestinal manifestations (EIMs), family history, and age at IBD diagnosis.
      RESULTS: For all IBD diagnoses, more sigmoid inflammation occurred in cases with
      diverticular disease: 82% versus 65% for controls (P = 0.005), and in the rectum:
      85% versus 69% for controls (P = 0.005). In the Crohn's disease with
      diverticulosis subset, sigmoid inflammation was more common: 70% versus 42% for
      controls (P = 0.007), and in the rectum: 70% versus 46% for controls (P = 0.02).
      Disease distribution was otherwise similar throughout the colon, ileum, and
      jejunum. The incidence of strictures (P = 0.99) and fistulae (P = 0.69) was
      similar. EIMs were more frequent in cases with diverticulosis: 28% versus 16% (P
      = 0.05). Family history of IBD was similar: 26% for cases and 16% for controls (P
      = 0.12). Age at IBD diagnosis was significantly greater in diverticulosis cases
      compared with controls: 51.5 years (+/-17.6) versus 42.8 years (+/- 17.5) (P <
      0.001), respectively. CONCLUSIONS: We observed an increased frequency of sigmoid
      and rectal inflammation, EIMs, and an older age of IBD onset in cases with
      diverticulosis. This suggests a role for diverticula in IBD beyond that of a mere
      coincidental finding.

PMID- 16633105
TI  - Interferon-induced depression in chronic hepatitis C: a review of its prevalence,
      risk factors, biology, and treatment approaches.
AB  - Hepatitis C viral infection is a global health problem that affects approximately
      4 million people in the United States. Combination treatment with pegylated
      interferon (IFN)-alpha plus ribavirin has been shown to be most effective in
      treating patients with chronic hepatitis C (CHC). Despite its efficacy, one of
      the most common side effects of this regimen is depression. Whereas IFN-alpha has
      been found to induce depression in chronic myelogenous leukemia, melanoma, and
      renal cell carcinoma, CHC patients may be especially prone to develop IFN-induced
      depression. This review includes a summary of differences between IFN-alpha and
      IFN-beta and addresses whether pegylation of IFN (versus nonpegylated IFN) gives
      rise to a treatment with reduced potential to induce depressive symptoms.
      Consideration is also given to evidence showing that treatment with ribavirin may
      contribute to IFN-induced depression. Thyroid disorders and anemia (as well as
      other medical conditions) have also been associated with IFN exposure and may
      account for some incidences of depression in CHC patients. Evidence is reviewed
      indicating that prior psychiatric and mood disorders (especially previous
      episodes of major depressive disorder), just prior to IFN treatment, contribute
      to the propensity to develop depression during treatment. In addition, a brief
      description is provided of potential biological mechanisms of IFN-induced
      depression (ie, monoamines, hypothalamic-pituitary-adrenocortical [HPA] axis,
      proinflammatory cytokines, peptidases, intercellular adhesion molecule-1, and
      nitric oxide). Finally, a discussion is provided on the use of antidepressants as
      a preventative versus restorative treatment, including a commentary on risks of
      using antidepressants in this patient population.

PMID- 16633106
TI  - Utility of bile duct brushings for the early detection of cholangiocarcinoma in
      patients with primary sclerosing cholangitis.
AB  - BACKGROUND: In patients with primary sclerosing cholangitis, there are no
      reliable markers or imaging modalities to detect malignant changes or early
      cholangiocarcinoma when curative interventions may still be possible. METHODS:
      Clinical features and outcomes were evaluated for 47 patients who underwent 101
      endoscopic retrograde cholangiopancreatography (ERCP) procedures with bile duct
      brushings and cytopathologic examination for the detection of malignant changes
      between January 2001 and 2004. Bile duct cytology was characterized as
      unsatisfactory, benign, atypical, or malignant. RESULTS: Fifteen patients had at
      least one sample that was abnormal. Patients with abnormal findings were older (P
      = 0.03); otherwise the groups were similar. Three of six patients with marked
      atypia have undergone transplantation for these abnormal findings, and of these,
      two had cholangiocarcinoma and one had no cancer detected in the explant. Of the
      nine patients with focal atypia, seven are doing well, one underwent
      transplantation for marked atypia seen on brushings at another hospital, and the
      other underwent transplantation for decompensated cirrhosis. Two patients with
      benign findings developed cholangiocarcinoma, whereas 29 others have not.
      CONCLUSION: Cytopathologic examination of bile duct brushings taken at ERCP may
      be useful for the early detection of malignant changes in patients with primary
      sclerosing cholangitis. However, long-term prospective studies are needed to
      confirm the utility of surveillance ERCP and brushings.

PMID- 16633107
TI  - The effects of treatment with octreotide, diuretics, or both on portal
      hemodynamics in nonazotemic cirrhotic patients with ascites.
AB  - GOALS: To evaluate the effects of diuretic treatment, octreotide, or both on
      portal hemodynamics in nonazotemic cirrhotic patients with ascites. BACKGROUND:
      Diuretics and octreotide have been associated with a decrease in portal pressure
      in cirrhotic patients, suggested to be mediated by plasma volume depletion and
      splanchnic vasoconstriction, respectively. However, liver cirrhosis is
      characterized by activation of the renin-angiotensin-aldosterone axis, which
      increases hepatic vascular resistance and is augmented or suppressed by diuretics
      or octreotide, respectively. STUDY: Twenty nonazotemic cirrhotic patients with
      ascites were treated with furosemide and spironolactone. Of them, 10 (group 1)
      discontinued diuretic treatment for 7 days. Thereafter for 5 days, each patient
      received subcutaneous octreotide, 300 microg twice per day; ten of them (group 2)
      received the octreotide in addition to their usual diuretic treatment. Portal and
      systemic hemodynamics with Doppler ultrasound and endogenous vasoactive systems
      were evaluated while the patients received diuretics (both groups), after
      discontinuation of diuretics (group 1), and after octreotide administration (both
      groups). RESULTS: The withdrawal of diuretics did not alter portal hemodynamics,
      but it impaired systemic hemodynamics and suppressed the renin-aldosterone axis.
      The addition of octreotide to diuretic treatment but not octreotide alone
      improved portal and systemic hemodynamics. In both groups the initiation of
      octreotide administration suppressed the renin-aldosterone axis and plasma
      glucagon levels. CONCLUSIONS: In nonazotemic cirrhotic patients with ascites, the
      combination of diuretics and octreotide improves systemic hemodynamics and
      inhibits the diuretic-related component of the activated renin-aldosterone axis,
      which in turn augments the portal hypotensive effect of diuretic-induced plasma
      volume depletion.

PMID- 16633108
TI  - Rebiopsy in patients with untreated hepatitis C: a useful procedure.
AB  - BACKGROUND: The progression of fibrosis in the early stages of chronic hepatitis
      C virus is variable, and the ideal interval to perform a new biopsy in untreated
      patients is still unknown. AIMS: We evaluated the histologic progression of
      patients with untreated hepatitis C virus with two liver biopsies and correlated
      disease progression with demographic, epidemiologic, biochemical, and histologic
      variables. PATIENTS AND METHODS: Untreated hepatitis C virus-infected patients
      with two liver biopsies at a minimum interval of 1 year were studied. Gender,
      age, parenteral risk factors, duration of infection, alcohol intake, alanine
      aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and
      histologic findings were analyzed. RESULTS: Fifty-five patients were included.
      The first biopsy showed low grades of fibrosis and periportal necroinflammatory
      activity in 93%. A second biopsy was performed after 39 +/- 14 months; 40% of
      patients showed a progression of fibrosis and/or periportal necroinflammation.
      Comparison between groups with and without histologic worsening revealed no
      differences in demographic, epidemiologic, biochemical, or histologic data.
      CONCLUSIONS: Histologic worsening occurred in 40% of untreated patients after 3.2
      years. No factor could be established at the first biopsy to predict which
      patients are at risk of progression. Thus, histologic reassessment between 3 and
      5 years seems to be the only approach to document disease progression and
      establish treatment indication.

PMID- 16633109
TI  - Chemotherapy-induced sclerosing cholangitis: long-term response to endoscopic
      therapy.
AB  - BACKGROUND: Hepatic arterial infusion of fluoropyrimidines has been widely used
      for the treatment of hepatic metastasis from colorectal cancer. One major
      complication of such treatment is biliary sclerosis resembling primary sclerosing
      cholangitis, which has an incidence ranging from 8% to 26%. AIM: We evaluated the
      efficacy and long-term outcome of endoscopic therapy in the management of
      chemotherapy-induced sclerosing cholangitis (CISC). METHODS: With the use of an
      endoscopic retrograde cholangiopancreatography (ERCP) database, all patients with
      a diagnosis of CISC who had endoscopic therapy between March 1995 and March 2005
      were identified. The indications, findings, therapies, and complications for all
      patients undergoing ERCP were recorded in this database. Additional information
      was obtained by review of medical records. RESULTS: Eleven patients (six men and
      five women) were identified. The mean age at presentation was 59.5 years (range,
      36-76 years). Cholangiogram findings revealed stricture confined to the common
      hepatic duct in two patients, involving the hilum in seven patients, involving
      the right and/or left main hepatic ducts in nine patients, and extending to the
      intrahepatic radicals in two patients. All patients had successful endoscopic
      therapy to alleviate the presenting symptom. The grade and extent of biliary
      strictures did not change in five patients, improved in one patient, recurred in
      two patients, and progressed in two patients over the follow-up period of 28.2
      months (range, 4-60 months). CONCLUSION: Although long-term follow-up of patients
      with CISC is limited by the dismal prognosis of the underlying malignancy, CISC
      has a recalcitrant pattern that rarely improves with endoscopic therapy. However,
      endoscopic therapy seems to be an effective method of palliation.

PMID- 16633110
TI  - Progression to cirrhosis in Latinos with chronic hepatitis C: differences in
      Puerto Ricans with and without human immunodeficiency virus coinfection and along
      gender.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in Latinos. There is
      some evidence that progression to cirrhosis is more rapid. END POINTS: To
      calculate time of cirrhosis from time of HCV infection in a large Latino
      population. Other end points were to assess variables that predict cirrhosis and
      the effect of gender, alcohol, and human immunodeficiency virus (HIV) infection
      status on time to cirrhosis. METHODS: Four hundred sixty-nine Latino patients
      evaluated at a referral center in Puerto Rico were included. Several demographic
      parameters, such as risk factors, estimated duration of HCV infection, alcohol
      use, HIV status, and findings from the usual HCV and HIV laboratory tests were
      noted. All patients had liver biopsy specimens assessed by Ishak score. RESULTS:
      Monoinfected and coinfected latinos have a median cumulative risk/hazard for
      cirrhosis of 42.0 vs. 32.0 years after infection (P = 0.0016). The median age of
      cirrhotic patients is 53.0 years in monoinfections and 42.0 years in coinfection.
      Among coinfected patients there is no gender-associated difference in time to
      onset of cirrhosis (P = 0.785). Among monoinfected patients, males have a shorter
      median risk/hazard to cirrhosis than females (11.0-year difference; P = 0.05) and
      have a shorter time until onset of cirrhosis by fibrosis progression rate (FPR)
      (33.33 vs. 41.66 years; P = 0.021). There is no difference between male patients
      with regard to HIV status (P = 0.199). Alcohol use is significant in monoinfected
      males (59.2 g/day) vs. females (11.4 g/day; P = 0.001). Variables that predict
      cirrhosis are male sex, age, and Ishak grade in monoinfected patients and alanine
      aminotransferase value in coinfected patients. CONCLUSIONS: Puerto Ricans with
      HCV have a median risk/hazard time to cirrhosis at younger age than other
      populations. Males who are HIV/HCV-coinfected have the same median risk/hazard
      and time to cirrhosis than those monoinfected with HCV. Special attention for
      early diagnosis and treatment is mandatory.

PMID- 16633111
TI  - Autoimmune disorders during interferon therapy in a patient with chronic
      hepatitis C infection: how many of them can be observed in a single patient?

PMID- 16633112
TI  - Massive gastrointestinal bleeding from an unusual source.

PMID- 16633113
TI  - Comment on Pitchumoni et al.

PMID- 16633116
TI  - Protracted hiccups due to severe erosive esophagitis: a case series.
AB  - BACKGROUND: Hiccups although a common annoyance of life, have been linked with
      significant morbidity and even death. There are numerous causes of prolonged
      hiccups, including diseases of the gastrointestinal tract. Hiccups are reported
      to represent an atypical manifestation of gastroesophageal reflux disease. CASES:
      We report 4 cases of prolonged hiccups in patients who failed to respond to
      initial treatment with abortive neurologic medications and who subsequently
      improved on proton-pump inhibitors. Endoscopic examination revealed severe reflux
      esophagitis. CONCLUSION: Hiccups are an atypical manifestation and may represent
      a more severe course of gastroesophageal reflux disease.

PMID- 16633117
TI  - Single-dose quinolone treatment in acute gastroenteritis.
AB  - BACKGROUND: Acute diarrhea is a common disease worldwide and in Israel, a
      Mediterranean country. Acute bacterial gastroenteritis (ABGE) is the leading
      cause of severe diarrhea in Israel in summer and early autumn. Although there are
      some reports showing some benefit from empiric antibiotic therapy in acute
      gastroenteritis, most are old reports using nondefinitive diagnostic criteria and
      using 5-day antibiotic regimens. AIMS: 1. To examine the efficiency of antibiotic
      therapy in relatively severe ABGE in general. 2. To check the efficiency of the
      different types of quinolones in the treatment of ABGE. 3. To compare various
      therapy regimens. METHODS: All patients admitted to the Barzilai Medical Center
      emergency room during the period June to October in 2002-2004 who were defined by
      protocol as having relatively severe gastroenteritis and required hospitalization
      in the Department of Internal Medicine were included in the study. All were
      randomized either to a supportive treatment only group (STG) or to the antibiotic
      treatment group (ATG) of ofloxacin or levofloxacin with a single dose or BID for
      5 days in addition to STGs. All patients were interviewed a week later about
      their medical history and duration of symptomatology. RESULTS: One hundred thirty
      nine patients were found eligible for the study in the above-mentioned period.
      Abdominal pain resolved 1.3 days earlier in the ATG in comparison to the STG
      whereas vomiting and diarrhea disappeared 1.0 and 0.8 days earlier, respectively,
      in the ATG versus the STG. In terms of fever abatement there was no difference
      between the regimens and no significant difference in symptomatology
      disappearance between various types of quinolones used or between the single
      antibiotic dose regimen and the 5-day antibiotic regimen groups. CONCLUSIONS: 1.
      Antibiotic therapy was found to shorten duration of symptoms in patients with
      relatively severe gastroenteritis. 2. Single-dose therapy is as effective and
      certainly significantly more cost effective in comparison to the 5-day antibiotic
      treatment regimen.

PMID- 16633118
TI  - Serum ghrelin levels in children with celiac disease.
AB  - OBJECTIVES: Ghrelin, a gastrointestinal hormone, has effects on nutrient intake
      and growth. Because celiac disease (CD) has intestinal histopathologic
      alterations and subsequent malnutrition and/or growth failure, we hypothesized
      that there would be alterations in serum ghrelin levels of those patients. In
      this study, we aimed to determine serum ghrelin levels in childhood CD, to
      observe probable alterations under gluten-free diet (GFD), and to see whether
      there is a relationship between ghrelin levels and the presentation of the
      disease and/or diet compliance. METHODS: Thirty-six children with CD and 10
      healthy children were included. Serum fasting ghrelin level was measured using
      radioimmunoassay method. After 6 months under GFD, sera of 19 patients were
      retested for ghrelin level. RESULTS: Mean serum ghrelin levels in children with
      CD and in controls were 478.2+/-154.6 and 108.3+/-49.1 pg/mL, respectively
      (P<0.001). Serum ghrelin level was not different in different clinical
      presentations. Ghrelin was negatively correlated with body mass index, both in
      healthy children and in children with CD on admission (P<0.01). Ghrelin level was
      lower after 6 months under GFDcompared with the level detected on admission
      (P<0.001), but was still higher compared with that of healthy children (P<0.001).
      Strict diet compliance lowered ghrelin level, although not statistically.
      CONCLUSIONS: Ghrelin is increased in childhood CD and is responsive to GFD.
      Further studies are needed to clarify the mechanism underlying its action in CD.

PMID- 16633119
TI  - Alexithymia is associated with gastrointestinal symptoms, but does not predict
      endoscopy outcome in patients with gastrointestinal symptoms.
AB  - BACKGROUND: Alexithymia, where a person has difficulty in distinguishing between
      emotions and bodily sensations, is considered to be a character trait and a
      vulnerability factor for various psychosomatic disorders. Assessing alexithymia
      in patients with gastrointestinal (GI) symptoms before endoscopy might therefore
      be useful in selecting patients who are more prone to functional GI disorders.
      GOAL: To determine whether alexithymia might be a useful factor in predicting GI
      endoscopy outcomes. STUDY: Patients referred for endoscopy between February 2002
      and February 2004 were enrolled. They were asked to report alexithymia on the
      Toronto Alexithymia Scale-20 2 weeks before endoscopy. Information about
      endoscopic diagnoses was obtained from medical files. RESULTS: A total of 1141
      subjects was included (49% male), of whom 245 (21%) reported alexithymia. There
      was no difference in mean+/-SD alexithymia scores between patients with (51+/-12)
      and without (50+/-12) an endoscopic organic abnormality at GI endoscopy. When
      divided into subgroups, according to the most prominent finding at either upper
      or lower GI endoscopy, there was no association with alexithymia. Patients with
      alexithymia reported a worse sensation of GI symptoms during the last weeks
      before enrollment in the study (mean+/-SD symptom severity score: 42+/-34 vs.
      34+/-30, respectively; P<0.01). CONCLUSIONS: Alexithymia is not associated with
      endoscopic findings, and has therefore no additive value in predicting endoscopy
      outcomes. Patients with alexithymia more often present with a higher number and
      more severe GI symptoms.

PMID- 16633120
TI  - Acceptance of telemanagement is high in patients with inflammatory bowel disease.
AB  - GOALS: Assess acceptance and attitudes regarding telemanagement (HAT) in patients
      with inflammatory bowel disease (IBD). BACKGROUND: Noncompliance is a barrier to
      successful outcomes in patients with IBD. Novel methods for monitoring and
      assessing compliance are needed. STUDY: HAT consists of a laptop connected to a
      weight scale. HAT prompts patients to respond to questions about symptoms,
      medication side effects, and compliance. Ten consecutive adult patients with IBD
      were trained to use HAT. Attitudinal surveys and structured qualitative
      interviews were performed at the end of the session. RESULTS: Twenty percent of
      patients had never used a computer at home. All patients reported that use of the
      computer and self-testing was not complicated. All patients reported that the
      symptom diary and questions on side effects were easy to answer. All patients
      reported that self-testing took little time. Eighty percent said that testing
      would not interfere with usual activities, that they could comply with testing 3
      times/wk, and that they would agree to use the system in the future. CONCLUSIONS:
      Improved methods of monitoring are needed for patients with IBD. Patients with
      IBD can be easily trained to use HAT, and patient acceptance is high. Further
      studies are needed to determine the clinical impact of HAT in IBD.

PMID- 16633121
TI  - Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis.
AB  - GOALS: The prognostic importance of interleukin-6 (IL-6), IL-8, and IL-10 in the
      prediction of acute pancreatitis severity. BACKGROUND: Early assessment of
      severity in acute pancreatitis could help the patients who are at risk of
      developing complications. Unfortunately, the used prognostic scoring systems
      generally are only moderately accurate in assessing disease severity. STUDY: We
      studied 117 consecutive patients with a diagnosis of acute pancreatitis admitted
      to our hospital during the past 2 years. Laboratory parameters and cytokines were
      analyzed from serum taken routinely on admission. Severity criteria were noted
      for each patient using Ranson, Glasgow, and APACHE II scoring systems. Local and
      systemic complications, developed during a follow-up period, were classified by
      Atlanta criteria. RESULTS: IL-6 was the only parameter that statistically
      significantly predicted complicated acute pancreatitis (P<0.05). IL-8 and IL-10
      and the 3 prognostic scoring systems used did not properly assess complicated
      versus noncomplicated acute pancreatitis. CONCLUSIONS: Our prospective study
      supported the potential importance of IL-6 in the early assessment of complicated
      acute pancreatitis, but also suggested that pancreatitis classified as
      complicated in a large number of patients could not be correctly predicted with
      the Ranson, Glasgow, and APACHE II scoring systems.

PMID- 16633122
TI  - Clearance of irretrievable bile duct and pancreatic duct stones by extracorporeal
      shockwave lithotripsy, using a transportable device: effectiveness and medium
      term results.
AB  - BACKGROUND AND GOALS: Extracorporeal shockwave lithotripsy (ESWL) is an
      established treatment of irretrievable biliary and pancreatic stones, but the
      cost of the shockwave generators limits its widespread use. We revised data about
      the effectiveness of our treatment for refractory stones using a transportable
      shockwave generator. STUDY: We retrospectively evaluated the short and medium
      term outcomes of patients who underwent ESWL using a transportable
      electromagnetic shockwave generator between 1998 and 2003 at our unit, for the
      treatment of irretrievable bile duct or pancreatic duct stones. All patients
      received intravenous conscious sedation and antibiotic prophylaxis. RESULTS:
      Complete stone clearance was achieved in 70/82 patients (85.4%), in 66 of the
      patients (94.2%) with 1 session of ESWL. Despite the insertion of a stent in the
      bile duct, 2 patients had moderate cholangitis, while they waited for the next
      ESWL session. We did not record any moderate-severe complication of ESWL, but 2
      patients underwent surgery owing to perforation/bleeding during endoscopic
      removal of residual fragments. A symptomatic recurrence of stones was recorded in
      10/69 (14.5%) patients, who had been previously cleared and whose follow-up data
      (median follow-up 29 mo; range 7 to 66) were available. CONCLUSIONS: We obtained
      satisfactory stone clearance by using a transportable shockwave generator. Most
      patients required 1 session. Our experience confirmed the safety of the
      treatment, even though patients may experience cholangitis while awaiting
      definitive treatment. The use of a transportable ESWL generator may be a valuable
      option in centers, while ensuring a sufficient proficiency in biliary endoscopy.

PMID- 16633123
TI  - Social stigmatization and hepatitis C virus infection.
AB  - GOAL: Our aim was to assess stigmatization by evaluating the impact of hepatitis
      C virus (HCV) on social interactions, feelings of rejection, internalized shame,
      and financial insecurity, and behavior. BACKGROUND: HCV patients suffer from
      slowly progressive disease. Although much research has improved the long-term
      prognosis of chronic HCV, quality of life may be affected by perceived social
      stigmatization. STUDY: In a cross-sectional study, HCV patients without cirrhosis
      or significant comorbidities were recruited from the University of North Carolina
      viral hepatitis clinic. Subjects completed a questionnaire administered by a
      trained interviewer that assessed changes in sexual behavior, personal hygiene
      habits, social function, and interactions. Additionally, subjects completed
      validated, standardized questionnaires, the Health Status Questionnaire, and the
      SCL-90-R. Frequencies were calculated for the prevalence of stigmatization and
      altered social interaction. Correlations between education and behavior changes
      were assessed. A series of multivariate analyses controlling for age, sex, and
      education were performed to assess the association between HCV acquisition risk
      and stigmatization. RESULTS: One hundred seventy-five of 217 potential subjects
      (81%) participated in the survey. The average age was 45.2+/-7.7 years. Fifty
      five percent were men and 53% were single. Twenty-nine percent had some college
      education. Risk factors for HCV acquisition included transfusion (21%) and
      injection drug use (29%), whereas 32% had an unknown mode of infection. Among
      common activities, 47% were less likely to share drinking glasses, 14% were less
      likely to prepare food, and one-third of subjects were less likely to share a
      towel. Thirty-five percent of respondents reported changes in their sexual
      practices. Decreased frequency of kissing and sexual intercourse was reported in
      20% and 27% of individuals, respectively. Almost half of the single subjects
      reported increased use of condoms compared with only 20% among married couples.
      The majority of subjects perceived financial insecurity, internalized shame, and
      social rejection. Only 39% reported health impairment. Education level did not
      influence behavior change. CONCLUSION: The majority of HCV subjects alter common
      behaviors and report financial insecurity, internalized shame, and social
      rejection, regardless of the method of HCV acquisition or socioeconomic status.
      These findings indicate that all HCV individuals be counseled and encouraged to
      participate in educational programs at the time of diagnosis to reduce
      unnecessary behavioral changes and stigmatization perceptions to improve quality
      of life.

PMID- 16633124
TI  - Acute colonic pseudo-obstruction after colonoscopy in a young woman on narcotics.

PMID- 16633125
TI  - Incidental detection of Ascaris lumbricoides by wireless capsule endoscopy.

PMID- 16633126
TI  - Portal, splenic, and superior mesenteric vein thrombosis in a patient with latent
      essential thrombocythemia and hyperhomocysteinemia.

PMID- 16633128
TI  - Probiotics and the immune response.
AB  - Beneficial effects exerted by probiotic bacteria in the treatment of human
      disease may be broadly classified as those effects which arise due to activity in
      the large intestine and are related to colonization or inhibition of pathogen
      growth; and those effects which arise in both the small and large intestine, and
      are related to enhancement of the host immune response and intestinal barrier
      function. In a strain dependent fashion, probiotic bacteria can enhance
      intestinal barrier function and modulate signal transduction pathways and gene
      expression in epithelial and immune cells. Oral administration of live probiotics
      and bacterial structural components can also differentially modulate dendritic
      cells resulting in an increased production of IL-10 and regulatory T cells. Both
      innate and adaptive immune responses can be modulated by probiotic bacteria.

PMID- 16633129
TI  - Colonic health: fermentation and short chain fatty acids.
AB  - Interest has been recently rekindled in short chain fatty acids (SCFAs) with the
      emergence of prebiotics and probiotics aimed at improving colonic and systemic
      health. Dietary carbohydrates, specifically resistant starches and dietary fiber,
      are substrates for fermentation that produce SCFAs, primarily acetate,
      propionate, and butyrate, as end products. The rate and amount of SCFA production
      depends on the species and amounts of microflora present in the colon, the
      substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is
      the major energy source for colonocytes. Propionate is largely taken up by the
      liver. Acetate enters the peripheral circulation to be metabolized by peripheral
      tissues. Specific SCFA may reduce the risk of developing gastrointestinal
      disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in
      the colon, and after absorption it has been shown to increase cholesterol
      synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit
      cholesterol synthesis. Therefore, substrates that can decrease the acetate:
      propionate ratio may reduce serum lipids and possibly cardiovascular disease
      risk. Butyrate has been studied for its role in nourishing the colonic mucosa and
      in the prevention of cancer of the colon, by promoting cell differentiation, cell
      cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme
      histone deacetylase and decreasing the transformation of primary to secondary
      bile acids as a result of colonic acidification. Therefore, a greater increase in
      SCFA production and potentially a greater delivery of SCFA, specifically
      butyrate, to the distal colon may result in a protective effect. Butyrate
      irrigation (enema) has also been suggested in the treatment of colitis. More
      human studies are now needed, especially, given the diverse nature of
      carbohydrate substrates and the SCFA patterns resulting from their fermentation.
      Short-term and long-term human studies are particularly required on SCFAs in
      relation to markers of cancer risk. These studies will be key to the success of
      dietary recommendations to maximize colonic disease prevention.

PMID- 16633130
TI  - Probiotics for children: use in diarrhea.
AB  - The use of probiotics in diarrheal diseases of children is increasing.
      Probiotics, mostly lactic acid bacteria such as Lactobacilli and Bifidobacteria,
      but also the yeast Saccharomyces boulardii, have been tried in many double
      blinded, randomized, placebo-controlled studies, and several well-conducted meta
      analyses are now available. There is some evidence of efficacy in the prevention
      of community-acquired and nosocomial diarrhea. More solid evidence of efficacy is
      found in the treatment of sporadic, infectious diarrhea, where several
      probiotics, and especially Lactobacillus GG, have been found capable of reducing
      by approximately 1 day the duration of diarrhea, shorten the initial phase of
      watery stools, and reducing hospital stay in developed countries. The effect is
      best documented in viral diarrheas. Although there are valid conceptual premises
      for probiotics to be helpful in inflammatory bowel diseases, only 1 trial has
      been published in children, showing Lactobacillus GG not to be superior to
      placebo in maintaining remission of Crohn disease. All considered, more research
      is needed for a better understanding of the role of probiotics in
      gastrointestinal diseases of children, addressing issues such as
      pharmacokinetics, mechanism of action, and role of specific probiotics, alone or
      in combination, in different disorders.

PMID- 16633131
TI  - Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium
      difficile diarrhea.
AB  - Antibiotic-associated diarrhea is a common clinical problem occurring in up to
      25% of patients, with diarrhea owing to Clostridium difficile accounting for up
      to a quarter of cases. The clinical and economic costs of antibiotic-associated
      diarrhea are significant and better treatments are needed. Probiotics may offer
      potential effective therapy for antibiotic-associated diarrhea by restoring
      intestinal microbial balance. A number of different probiotics have been
      evaluated in the prevention and treatment of antibiotic-associated diarrhea in
      adults and children, including the nonpathogenic yeast Saccharomyces boulardii
      and multiple lactic-acid fermenting bacteria such as Lactobacillus rhamnosus GG
      (LGG). A careful review of the literature supports the efficacy of S. boulardii
      in the prevention of antibiotic-associated diarrhea recurrent C. difficile
      infection in adults, whereas LGG is useful in the treatment of antibiotic
      associated diarrhea in children. Not enough data exist to currently support the
      use of other probiotic preparations in these conditions. Although generally safe
      and well tolerated, both S. boulardii and LGG should be used cautiously in
      immunocompromised patients. Further study of probiotics, including large, well
      designed, randomized controlled dose-ranging trials, comparative trials, and cost
      benefit analyses are necessary.

PMID- 16633132
TI  - Probiotics for women's health.
AB  - GOALS: The goals of this research were 2-fold: (1) to determine whether a
      commercially available probiotic mixture (VSL-3) could survive and grow in a
      continuous culture system simulating the vaginal environment and (2) to determine
      whether the probiotic mixture was capable of suppressing the growth of a known
      vaginal vault pathogen, Gardnerella vaginalis. BACKGROUND: An abnormal vaginal
      microflora, such as that associated with bacterial vaginosis (BV) is an important
      health issue for women. In addition, the association of this condition with
      preterm labor and delivery suggests that control of BV may impact the number of
      preterm births. Interventional trials with antibiotics have received mixed
      reviews and other interventional options, including the use of probiotics, are
      being considered. STUDY: A well-documented continuous culture system has been
      used to determine whether VSL-3 can survive and grow in conditions simulating a
      vaginal environment. In addition, the ability of VSL-3 to inhibit the growth of a
      known vaginal vault pathogen, G. vaginalis, has been determined. RESULTS: The
      probiotic mixture was shown to survive and maintain itself within the
      fermentation vessel of the continuous culture system over an extended period of
      time. This mixture, when challenged with a known pathogen, was also shown to
      suppress the growth of G. vaginalis. CONCLUSIONS: It may be feasible to use
      probiotics as interventional therapy to suppress the growth of pathogens within
      the vaginal vault associated with BV.

PMID- 16633133
TI  - Probiotics in the treatment of inflammatory bowel disease.
AB  - The demonstration that immune and epithelial cells can discriminate between
      different microbial species has extended our understanding of the actions of
      probiotics beyond simple antimicrobial concepts. Several probiotic mechanisms of
      action, relative to inflammatory bowel disease, have been elucidated: (1)
      competitive exclusion, whereby probiotics compete with microbial pathogens; (2)
      immunomodulation and/or stimulation of an immune response; (3) antimicrobial
      activity and suppression of pathogen growth; (4) enhancement of barrier activity;
      and (5) induction of T cell apoptosis. The unraveling of these mechanisms of
      action has led to new support for the use of probiotics in the management of
      clinical inflammatory bowel disease. While level 1 evidence now supports the
      therapeutic use of some probiotics in the maintenance treatment of pouchitis,
      only level 2 and 3 evidence are currently available in support of the use of
      probiotics in the treatment of ulcerative colitis and Crohn's disease.
      Nevertheless, one significant and consistent finding has emerged over the course
      of research in the past year: not all probiotic bacteria have similar therapeutic
      effects. Rigorously designed, controlled clinical trials, to investigate the
      unresolved issues related to efficacy, dose, duration of use, single or
      multistrain formulation, and the concomitant use of prebiotics, synbiotics or
      antibiotics, are vital.

PMID- 16633134
TI  - Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and
      evidence of clinical efficacy.
AB  - The irritable bowel syndrome (IBS) follows an acute, presumably infectious
      diarrheal illness in approximately 15% of patients. There may be a persistent,
      mild inflammatory state with changes in mucosal function or structure. Changes in
      the colonic bacterial flora reported in IBS seem related to predominant bowel.
      Colonic bacteria normally metabolize nutrients with the formation of gas and
      short chain fatty acids. The latter may induce propulsive contractions and
      accelerate colonic transit or they may enhance fluid and sodium absorption in the
      colon. This review addresses the mechanisms, rationale and current evidence for
      the efficacy of probiotics, including Lactobacilli, Bifidobacteria, and VSL#3, in
      the treatment of IBS. The mechanisms influenced by probiotics include immune
      function, motility, and the intraluminal milieu. Probiotics may suppress the low
      grade inflammation associated with IBS or restore normal local immune function.
      Lactobacilli and Bifidobacteria subspecies are able to deconjugate and absorb
      bile acids, potentially reducing the colonic mucosal secretion of mucin and
      fluids that may contribute to functional diarrhea or IBS with diarrhea.
      Therapeutic trials show the potential benefit of Bifidobacteria or Lactobacilli
      species alone or in the specific probiotic combination, VSL#3, on symptoms in
      IBS. Colonic transit was retarded in IBS patients treated with VSL#3 without
      induction of significant changes in bowel function. In summary, probiotics are
      promising therapies in IBS.

PMID- 16633135
TI  - Probiotics and chronic disease.
AB  - In today's climate, changed lifestyles and the increased use of antibiotics are
      significant factors that affect the preservation of a healthy intestinal
      microflora. The concept of probiotics is to restore and maintain a microflora
      advantageous to the human body. Probiotics are found in a number of fermented
      dairy products, infant formula, and dietary supplements. Basic research on
      probiotics has suggested several modes of action beneficial for the human body
      and clinical research has proven its preventive and curative features in
      different intestinal and extraintestinal diseases. Chronic diseases cause
      considerable disablement in patients and represent a substantial economic burden
      on healthcare resources. Research has demonstrated a crucial role of nutrition in
      the prevention of chronic disease. Thus, positive, strain-specific effects of
      probiotics have been shown in diarrheal diseases, inflammatory bowel diseases,
      irritable bowel syndrome, and Helicobacter pylori-induced gastritis, and in
      atopic diseases and in the prevention of cancer. As the majority of probiotics
      naturally inhabit the human intestinal microflora, their use has been regarded as
      very safe. However, in view of the range of potential benefits on health that
      might be achieved by the use of some probiotic bacteria, major and thorough
      evaluation is still necessary. In conclusion, probiotics act as an adjuvant in
      the prevention and treatment of a wide variety of chronic diseases.

PMID- 16633136
TI  - Recommendations for probiotic use.
AB  - Probiotics are live microbial organisms that are administrated as supplements or
      in foods to benefit the host. It is the recommendation that they may be helpful
      in the prevention and treatment of acute diarrhea in adults and children, the
      prevention of antibiotic-associated diarrhea in adults and children, and the
      maintenance of remission and prevention of pouchitis. Although early results
      indicate that probiotics may also be useful in immunologic modulation to prevent
      atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis,
      and the irritable bowel syndrome, the studies available are not sufficient to say
      they are definitely helpful. Even fewer data are available to recommend
      probiotics for the treatment of H pylori and Crohn disease and for the prevention
      of cardiovascular risk factors or other degenerative diseases. Clearly, larger
      and better-designed studies of probiotics are necessary, including comparative
      and dose-ranging trials.

PMID- 16633137
TI  - High medication discontinuation rates in psychiatry: how often is it
      understandable?

PMID- 16633138
TI  - What is the optimal duration of a short-term antidepressant trial when treating
      geriatric depression?
AB  - BACKGROUND: To determine the optimal duration of an antidepressant trial in
      elderly patients, the authors examined the probability of eventually responding
      to treatment based on early improvement. METHODS: Four hundred seventy-two
      elderly patients with major depression (nonpsychotic, nonbipolar) were treated
      under protocolized conditions for up to 12 weeks and assessed weekly with the
      Hamilton Rating Scale for Depression. The probability of full response after 12
      weeks of treatment was calculated in patients who had not fully responded after
      periods of treatment that lasted for 4 to 10 weeks. RESULTS: Most of the patients
      who had shown a partial improvement after 4 weeks of treatment became full
      responders after 4 or more additional weeks of treatment. By contrast, only a few
      of those who were nonresponders became full responders even after up to 8
      additional weeks of treatment. CONCLUSIONS: After 4 weeks of treatment, it is
      possible to reliably identify a subgroup of elderly patients with depression who
      are more likely to benefit from a change in their treatment than from a few
      additional weeks of treatment with the same agent.

PMID- 16633139
TI  - Efficacy and tolerability of reboxetine compared with citalopram: a double-blind
      study in patients with major depressive disorder.
AB  - The objective of this study was to compare efficacy and tolerability of the
      selective noradrenaline reuptake inhibitor reboxetine with the selective
      serotonin reuptake inhibitor citalopram, in the treatment of major depressive
      disorder (MDD). In total, 357 outpatients with MDD were randomized to treatment
      with reboxetine 8-10 mg or citalopram 20-40 mg per day during 24 weeks. Primary
      end-point was change from baseline in the Hamilton Depression Rating Scale (HAM
      D, 21 items). Sexual function/dysfunction was measured by the Sexual Function
      scale (SF). Observed case analysis showed that both treatments yielded a gradual
      reduction of HAM-D scores: reboxetine with -21.4 and citalopram with -22.1 points
      (NS). LOCF analysis showed a greater reduction of the HAM-D scores with
      citalopram compared with reboxetine (-19.6 vs. -17.8; P = 0.034). The response
      rate was 90.3% for reboxetine and 92.7% for citalopram (NS). The most common side
      effect in the reboxetine group was dry mouth, and in the citalopram group sexual
      dysfunction. At week 24, anorgasmia was reported by 5.9% of the sexually active
      women in the reboxetine group vs 39% in the citalopram group. The dropout number
      was 91 in the reboxetine group, and 54 in the citalopram group. To summarize,
      both treatments gave a satisfactory antidepressant effect. The side effect
      profile differed between the groups, with a notably high prevalence of sexual
      dysfunctions in the citalopram group. The high number of dropouts in the
      reboxetine group, is considered as a result of the non-titration starting dose of
      8 mg reboxetine per day, which gave a high incidence of early side-effects.

PMID- 16633140
TI  - Risperidone-related weight gain: genetic and nongenetic predictors.
AB  - OBJECTIVE: A serious side effect of atypical antipsychotics is increased body
      weight, which leads to further morbidity and nonadherence to medication. It has
      been suggested that both genetic and nongenetic variables may influence
      antipsychotics-related weight gain. This study aimed to simultaneously explore
      the effects of multiple candidate genes and environment factors on body weight of
      schizophrenia patients who received risperidone, a commonly used atypical
      antipsychotic agent. METHODS: One hundred twenty-three ethnically Han Chinese
      inpatients with acutely exacerbated schizophrenia were given risperidone
      monotherapy for up to 42 days. Body weight and clinical manifestations were
      assessed biweekly. Drug efficacy was measured by the Positive and Negative
      Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom
      Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body
      weight as the response value. Potential prognostic factors were baseline body
      weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores,
      treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate
      genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic
      receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6
      (CYP2D6)]. Because there were repeated assessments, multiple linear regression
      with the generalized estimating equation (GEE) method was used to adjust the
      within-subject dependence. RESULTS: Of 15 genetic polymorphisms examined, 5-HT2A
      102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T
      significantly influenced body weight, and so did baseline body weight, age,
      gender, schizophrenia subtype, and treatment duration and efficacy. CONCLUSIONS:
      These results suggest that numerous genetic and nongenetic factors affect
      antipsychotics-related weight gain.

PMID- 16633141
TI  - Combined effects of itraconazole and CYP2D6*10 genetic polymorphism on the
      pharmacokinetics and pharmacodynamics of haloperidol in healthy subjects.
AB  - This study was to evaluate the combined effects of the CYP3A4 inhibitor
      itraconazole and the CYP2D6*10 genotype on the pharmacokinetics and
      pharmacodynamics of haloperidol, a substrate of both CYP2D6 and CYP3A4, in
      healthy subjects. Nineteen healthy volunteers whose CYP2D6 genotypes were
      predetermined were enrolled (9 for CYP2D6*1/*1 and 10 for CYP2D6*10/*10). Four
      subjects (1 for CYP2D6*1/*1 and 3 for CYP2D6*10/*10) did not complete the study
      because of adverse events. The pharmacokinetics of haloperidol and its
      pharmacodynamic effects measured for QTc prolongation and neurologic side effects
      were evaluated after a single dose of 5 mg haloperidol following a pretreatment
      of placebo or itraconazole at 200 mg/d for 10 days in a randomized crossover
      manner. Itraconazole pretreatment increased the mean area under the time
      concentration curves (AUCs) of haloperidol by 55% compared to placebo
      pretreatment (21.7 +/- 11.3 vs 33.5 +/- 29.3 ng h/mL). The subjects with
      CYP2D6*10/*10 genotype showed 81% higher AUC compared to that of subjects with
      CYP2D6*1/*1 genotype (27.6 +/- 22.2 vs 50.2 +/- 47.1 ng h/mL). In the presence of
      itraconazole, subjects with CYP2D6*10/*10 showed 3-fold higher AUC of haloperidol
      compared to that of placebo pretreated subjects with CYP2D6*1/*1 genotype (21.7
      +/- 11.3 vs 66.7 +/- 62.1 ng h/mL; P < 0.05). The CYP2D6*10 genotype and
      itraconazole pretreatment decreased the oral clearance of haloperidol by 24% and
      25%, respectively, but without a statistical significance. In the subjects with
      both CYP2D6*10 genotype and itraconazole pretreatment, however, the oral
      clearance was significantly decreased to 42% of subjects with wild genotype in
      the placebo pretreatment (4.7 +/- 3.6 vs 2.0 +/- 1.9 L/h/kg; P < 0.05). Barnes
      Akathisia Rating Scale (BARS) of subjects with CYP2D6*10/*10 in the presence of
      itraconazole pretreatment was significantly higher than that of subjects with
      CYP2D6*1/*1 genotype in the period of placebo pretreatment. Except for this, all
      other pharmacodynamic estimations did not reach to statistical significance
      although each CYP2D6*10 genotype and itraconazole pretreatment caused higher
      value of UKU side effect and BARS scores. The moderate effect of CYP2D6*10
      genotype on the pharmacokinetics and pharmacodynamics of haloperidol seems to be
      augmented by the presence of itraconazole pretreatment.

PMID- 16633142
TI  - Effects of acute hypoglycemia on motivation and cognitive interference in people
      with type 1 diabetes.
AB  - AIMS: To examine the effect of acute hypoglycemia on motivation and cognitive
      interference in adult humans with type 1 diabetes. METHODS: A hyperinsulinemic
      glucose clamp was used to either maintain euglycemia (arterialized blood glucose
      4.5 mmol/L) or induce hypoglycemia (2.6 mmol/L) in 16 adults with type 1
      diabetes, each of whom were studied on 2 separate occasions in a counterbalanced
      order. During each study condition, the subjects completed parallel tests of
      cognitive function. The Dundee Stress State Questionnaire (DSSQ) was administered
      before and after the cognitive function tests. RESULTS: Hypoglycemia decreased
      task-relevant (P = 0.03) and increased task-irrelevant (P = 0.02) interference.
      Self-focus of attention was much higher after hypoglycemia than euglycemia (P =
      0.02). Motivation declined to a similar extent during the euglycemia and
      hypoglycemia conditions (P = 0.07). Hypoglycemia produced a negative mood state
      with a significant fall in energy levels (P = 0.03) and a concomitant rise in
      anxiety level (P = 0.05). The subjective perception of concentration was
      unaffected during hypoglycemia (P = 0.14), and the scores for control and
      confidence did not fall (P = 0.19). CONCLUSIONS: In people with type 1 diabetes,
      hypoglycemia causes a state of heightened self-awareness and distraction during
      active mental activity. This is likely to leave fewer processing resources
      available to allow completion of cognitive tasks. Acute hypoglycemia induces a
      state of significant worry and anxiety that is likely to affect the social,
      personal, and work activities of people with diabetes.

PMID- 16633143
TI  - Reboxetine versus fluvoxamine in the treatment of motor vehicle accident-related
      posttraumatic stress disorder: a double-blind, fixed-dosage, controlled trial.
AB  - BACKGROUND: Motor vehicle accidents (MVAs) are a leading cause of posttraumatic
      stress disorder (PTSD) in the general population. Alterations in norepinephrine
      and serotonin systems have been proposed as mechanisms involved in the
      pathophysiology of the condition, with treatment directed at these
      neurotransmitter systems. Reboxetine, a selective norepinephrine reuptake
      inhibitor, exhibits high affinity and selectivity for the human norepinephrine
      transporter. Inasmuch as PTSD may be associated with dysregulation of
      noradrenergic activity, the present double-blind randomized clinical trial
      intended to evaluate reboxetine's efficacy in the management of MVA-related PTSD
      and to compare its efficacy with a medication commonly used in PTSD, the
      selective serotonin reuptake inhibitor fluvoxamine. METHODS: Forty patients with
      MVA-related PTSD attending a local community mental health outpatient clinic were
      randomized to receive a fixed dose of either reboxetine (8 mg/d) or fluvoxamine
      (150 mg/d) in a double-blind fashion for a period of 8 weeks. RESULTS: At
      baseline and at study end point, the 2 subgroups demonstrated no statistical
      differences in scores on PTSD, depression, and anxiety rating scales. Both
      medications led to significant improvements in all clinical scales measured. Nine
      patients receiving reboxetine and 3 receiving fluvoxamine withdrew from the study
      because of side effects. CONCLUSIONS: Study observations indicate comparable
      efficacy of reboxetine and fluvoxamine in the management of MVA-related PTSD
      despite reboxetine's selective noradrenergic activity. Reboxetine appears to be
      at least as effective as fluvoxamine and may offer an alternative management
      option in this often difficult-to-treat and disabling condition. A lower and
      flexible reboxetine dosing schedule will be recommended for future research to
      improve its tolerability in PTSD patients.

PMID- 16633144
TI  - A 24-week randomized study of olanzapine versus ziprasidone in the treatment of
      schizophrenia or schizoaffective disorder in patients with prominent depressive
      symptoms.
AB  - OBJECTIVE: The objective of this study is to compare olanzapine with ziprasidone
      therapy in patients with schizophrenia or schizoaffective disorder and
      experiencing depressive symptoms. METHODS: This randomized, double-blind, 24
      week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192)
      for patients with schizophrenia or schizoaffective disorder and experiencing
      prominent depressive symptoms. Outcome measures included change in Calgary
      Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary
      outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales,
      Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF)
      scores for 24 weeks. Statistical analyses included mixed-effects model repeated
      measures (primary analysis) and change from baseline to last observation carried
      forward (LOCF). RESULTS: At baseline, patients had moderate depressive symptoms
      (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks,
      patients treated with olanzapine or ziprasidone had significant improvements on
      CDSS. Treatment group differences were not statistically significant (P = 0.493,
      mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine
      treated patients showed significantly greater improvements in depressive symptoms
      (results varied by depression measure and statistical approach) and GAF (P <
      0.017, LOCF). A significantly higher proportion of olanzapine-treated patients
      completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication
      (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients.
      Olanzapine-treated patients experienced significantly (P < 0.05) greater
      increases in triglycerides, HgbA1c, and weight. CONCLUSIONS: For 24 weeks,
      olanzapine-treated patients had greater and more sustained participation in
      treatment, during which time significantly greater improvements were observed in
      depressive symptoms and GAF scores, along with increases in weight and certain
      metabolic parameters as compared with ziprasidone-treated patients.

PMID- 16633145
TI  - A double-blind comparison of galantamine hydrogen bromide and placebo in adults
      with attention-deficit/hyperactivity disorder: a pilot study.
AB  - BACKGROUND: Galantamine hydrogen bromide (HBr) is a competitive and reversible
      inhibitor of acetylcholinesterase. Because of its cholinergic nicotinic mechanism
      of action, galantamine HBr was hypothesized to have therapeutic activity in the
      treatment of attention-deficit/hyperactivity disorder (ADHD). METHOD: We
      conducted a 12-week, double-blind, placebo-controlled, randomized clinical trial
      using daily doses of up to 24 mg/d of galantamine HBr in the treatment of adults
      who met full Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition criteria for ADHD with childhood-onset and persistent adult symptoms. All
      analyses were intention to treat with the last observation carried forward for
      subjects who did not complete the full study schedule. RESULTS: The mean daily
      doses at week 12 were 19.8 +/- 6.4 mg for galantamine HBr and 21.8 +/- 4.6 mg for
      placebo (P = 0.3). There was no statistically or clinically significant greater
      reduction in ADHD symptoms in subjects treated with galantamine HBr relative to
      those receiving placebo (P = 0.5). Using last observation carried forward, 4
      (22%) of 18 of patients receiving galantamine HBr were considered responders
      (much or very much improved on the Clinical Global Impression Improvement Scale
      and at least a 30% reduction on the ADHD Investigator Symptom Report Scale
      compared with 11% [2/18] on placebo; P = 0.4). CONCLUSION: These results do not
      support the clinical utility of galantamine HBr in the treatment of ADHD at the
      doses used in this pilot study.

PMID- 16633146
TI  - Risperidone-induced symptomatic hyperprolactinaemia in adolescents.
AB  - Studies performed in adult patients unambiguously demonstrate a marked effect of
      risperidone on prolactin blood levels, with possible clinical effects related to
      hyperprolactinemia, such as gynecomastia and galactorrhea. However, the largest
      study performed in children and adolescents showed a weak effect of risperidone
      on prolactin concentrations during short-term treatment and a negligible effect
      during long-term treatment, which was probably because of the relatively low
      dosages of risperidone used [approximately 0.04 mg/(kg x d)]. Among the 10
      psychotic adolescents treated with risperidone in our unit, we had 3 cases of
      gynecomastia in 3 male patients and 2 cases of galactorrhea in 2 female patients.
      The prolactin blood levels in these cases and in 3 other patients without
      apparent prolactin-related side effects were all above the normal range (median,
      59 ng/mL; range, 30-123 ng/mL). Thus, risperidone administered to adolescents at
      doses commonly used for the treatment of psychotic symptoms can strongly increase
      prolactin levels, with clinical consequences such as gynecomastia and/or
      galactorrhea. Given that the long-term effects of antipsychotic drug-induced
      hyperprolactinemia are not well documented, especially regarding osteopenia,
      infertility, growth, and pubertal delay, risperidone should be administered with
      caution to children and adolescents.

PMID- 16633147
TI  - Escitalopram, but not its major metabolites, exhibits antiplatelet activity in
      humans.
AB  - BACKGROUND: Clinical depression has been identified as an independent risk factor
      for increased mortality during follow-up in patients suffered from acute coronary
      events, whereas increased platelet activity has been proposed as one of the
      mechanisms for this association. Some evidence suggests that selective serotonin
      reuptake inhibitors and/or their metabolites exhibit potent antiplatelet
      properties. METHODS: We assessed the in vitro effects of preincubation with
      escalating (50-200 nmol/L) concentrations of escitalopram (ESC) S-desmethyl
      citalopram (S-DCT), and S-di-desmethyl-citalopram, (S-DCT) on platelet
      aggregation through the expression of major surface receptors using flow
      cytometry and quantitatively using platelet function analyzers in 20 healthy
      volunteers. RESULTS: Pretreatment of blood samples with ESC with ESC resulted in
      a significant inhibition of platelet aggregation induced by ADP (P = 0.0001) and
      by collagen with the highest dose (P = 0.001). Surface platelet expressions of
      glycoprotein Ib (CD42) (P = 0.04), lysosome associated membrane protein-3 (CD63)
      (P = 0.02), and GP37 (CD165) (P = 0.03) was decreased in the ESC-pretreated
      samples. Closure time by the Platelet Function Analyzer-100 analyzer was
      prolonged for the 200 nmol/L dose (P = 0.02), indicating platelet inhibition
      under high shear conditions. Two major metabolites of ESC, namely S-DCT and S
      DDCT, did not affect platelet activity. CONCLUSION: Escitalopram, but not its
      metabolites, exhibited selective inhibition of human platelet properties. The
      direct antiplatelet effect of ESC requires further prospective or ex vivo testing
      to determine the possible clinical advantage of this finding.

PMID- 16633148
TI  - Cognitive functioning in bipolar patients receiving lamotrigine: preliminary
      results.
AB  - Despite the increasing use of lamotrigine (LTG) in bipolar disorder, little is
      known about its impact on cognition in bipolar patients. Therefore, we have
      evaluated 33 bipolar I and II patients on cognitive measures (verbal memory,
      attention, executive functions) while receiving either LTG (n = 15) or another
      anticonvulsant (carbamazepine or valproate; n = 18). Patients receiving LTG were
      generally diagnosed as having bipolar II disorder, had experienced more
      depressive episodes but a lesser number of hospitalizations, and had better
      performance than the patients receiving carbamazepine or valproate on the verbal
      fluency task. A moderate effect size also suggests that both groups may differ on
      the immediate verbal memory test (California Verbal Learning Test). These
      preliminary results suggest a safer neurocognitive profile of LTG on bipolar
      patients, as compared with other anticonvulsants.

PMID- 16633149
TI  - Risk of mortality associated with antipsychotic and other neuropsychiatric drugs
      in pneumonia patients.
AB  - OBJECTIVE: To evaluate the use of typical and atypical antipsychotic medications
      and associated in-hospital mortality in a group of Veterans Administration (VA)
      patients with pneumonia. METHOD: Our cohort consisted of 14,057 VA patients
      admitted for pneumonia in fiscal year (FY) 2003. Exposure to typical and atypical
      antipsychotics and other neuropsychiatric drugs was based on a prescription
      within 120 days preceding admission. Multivariate models determined the odds of
      mortality associated with each drug class and risk adjusted for comorbidity,
      admission source, demographic factors, and concurrent mental health conditions.
      The referent group for each analysis was pneumonia patients not receiving
      neuropsychiatric drugs. RESULTS: In adjusted analyses, the odds of in-hospital
      mortality for VA patients admitted with pneumonia was higher for recent exposure
      to typical antipsychotics (OR = 1.51, 95% CI = 1.04-2.19; P = 0.03) when compared
      to patients not receiving neuropsychiatric medications. Patients exposed to
      atypical antipsychotics (OR = 1.20, 95% CI = 0.96-1.50, P = .10), tricyclic
      antidepressants (OR = 1.20, 95% CI = 0.44-1.55; P = 0.15), other antidepressants
      (OR = 1.07, 95% CI = 0.93-1.23; P = 0.37), or mood stabilizers (OR = 0.91, 95% CI
      = 0.73-1.14; P = 0.41) had no significant difference in in-hospital mortality.
      CONCLUSION: In spite of recent safety concerns for atypical antipsychotics, we
      found no increased risk of mortality in acutely ill pneumonia patients. Rather,
      we found a higher adjusted mortality rate for patients taking typical
      antipsychotics. The contrasting mortality risks for patients taking typical and
      atypical antipsychotics may represent unmeasured severity of illness or
      comorbidity. Regardless, any antipsychotics should be used with caution and the
      efficacy and safety of alternative agents should be considered.

PMID- 16633150
TI  - Time course of in vivo 5-HTT transporter occupancy by fluvoxamine.
AB  - The pharmacokinetics of drugs with specific binding sites in the brain needs to
      be evaluated at these sites. In this study, we measured the time course of the
      selective serotonin reuptake inhibitor fluvoxamine in the human brain based on
      serotonin transporter (5-HTT) occupancy by positron emission tomography.
      Consecutive positron emission tomography scans were performed using [11C]3-amino
      4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile before, 5 hours, 26 hours,
      and 53 hours after 50 mg of fluvoxamine administration in 6 healthy male
      volunteers (mean, 24.3 +/- 4.8 years). Quantification was performed using the
      multilinear reference tissue model 2. Mean 5-HTT occupancies were 72.9% +/- 4.9%
      at 5 hours, 50.3% +/- 11.0% at 26 hours, and 24.7% +/- 15.3% at 53 hours, and
      plasma concentrations were 13.9 +/- 5.5 ng/mL at 5 hours, 5.1 +/- 3.2 ng/mL at 26
      hours, and 1.5 +/- 1.7 ng/mL at 53 hours. The relationship between the plasma
      concentration of fluvoxamine and 5-HTT occupancy at these different time points
      was fitted to the law of mass action.

PMID- 16633151
TI  - Risk factors for extrapyramidal symptoms during treatment with selective
      serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin
      and dopamine transporter and receptor polymorphisms.
AB  - INTRODUCTION: Extrapyramidal symptoms (EPS) are rare adverse drug reactions to
      selective serotonin reuptake inhibitors (SSRIs). This study aimed to investigate
      the potential risk factors for EPS associated with SSRIs including polymorphisms
      of cytochrome P-450 isoenzymes, and serotonin and dopamine transporters and
      receptors. METHODS: All spontaneous adverse drug reaction reports received by the
      Swedish Medical Products Agency until December 1999 that were coded with EPS and
      judged to be at least possibly related to SSRI treatment were included in the
      study. Reporting physicians received a form for collection of relevant
      information including current and previous use of SSRIs and antipsychotics,
      alcohol or substance abuse, central nervous system damage, a history of epilepsy
      or EPS, and a family history of Parkinson disease. A blood sample was also
      requested for genotyping of selected cytochrome P-450, and serotonin and dopamine
      transporter and receptor mutations. RESULTS: A total of 64 cases of EPS were
      reported. Twenty-eight forms (46%) were returned, and 20 blood samples were
      obtained. Identified potential risk factors included age of 65 years or older and
      the presence of the A1 allele of the D2 dopamine receptor gene (DRD2) Taq1A
      polymorphism (relative risk, 2.4; 95% confidence interval, 1.2-4.5 vs literature
      controls). No relationship was apparent for sex, drug dose, or other genetic
      polymorphisms. At least 1 additional potential risk factor for EPS, such as a
      history of central nervous system damage, alcohol or substance abuse, epilepsy,
      Parkinson disease, previous or current exposure to antipsychotic drugs,
      concomitant treatment with other antidopaminergic or serotonergic agents, or a
      history of EPS, was found in 93% of the cases. CONCLUSION: The risk of EPS with
      SSRIs seems to increase with advanced age and with the presence of the A1 allele
      of DRD2 Taq1A polymorphism. Because of the small sample size of our study and the
      use of historical controls rather than patients who did not experience EPS during
      SSRIs treatment, the DRD2 finding is preliminary and needs to be replicated in
      other studies before firm conclusions can be drawn. At least 1 additional
      potential risk factor was found in almost all cases.

PMID- 16633152
TI  - Symptom-onset treatment for women with premenstrual dysphoric disorder.
AB  - Symptoms of premenstrual dysphoric disorder (PMDD) respond to serotonin reuptake
      inhibitors when treatment is limited to 14 days of the menstrual cycle. Many
      women have less than a week of symptoms, and shorter treatment intervals would
      further reduce medication exposure and costs. METHODS: Twenty women with PMDD
      were randomly assigned to either paroxetine CR or placebo for 1 cycle and crossed
      over to the other condition for a second cycle. Subjects initiated treatment when
      premenstrual symptoms began and stopped within 3 days of beginning menses.
      RESULTS: Women took capsules for an average of 9 days (range, 3-15 days),
      including the first few days of menses. Moderate "PMDD level" symptoms occurred
      in 1 subject (6%) for 2 days and 4 subjects (24%) for 1 day before starting
      paroxetine or placebo. Daily Record of Severity of Problems scores were lower in
      the paroxetine group compared with the placebo group, although the differences
      were not statistically significant. However, the mean on-treatment Inventory of
      Depressive Symptomatology (clinician-rated) score for the paroxetine group was
      17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean
      difference = 13.6, P = 0.009). Response (Clinical Global Impressions Scale score
      of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of
      those assigned to placebo (chi2(1) = 7.5, P = 0.006). Discontinuation symptoms
      did not differ in the groups. CONCLUSION: These data suggest the need to further
      evaluate symptom-onset treatment in a larger randomized clinical trial.

PMID- 16633153
TI  - Suicide rates in short-term randomized controlled trials of newer
      antidepressants.
AB  - Concerns have been raised about the appropriateness of placebo controls in
      clinical trials for major depressive disorder (MDD), given that there are
      approved treatments for this illness. Critics have argued that patients with
      untreated depression would be exposed to an unnecessary risk of suicide. There is
      also a competing concern that antidepressant drug treatment itself may induce
      suicidal behavior and thinking (suicidality). To examine this question, we have
      evaluated the rate of suicide in placebo- and active drug-treated groups of
      patients with MDD and various anxiety disorders participating in short-term
      randomized controlled trials (RCTs). We examined data from all manufacturer
      sponsored short-term RCTs of 9 commonly used antidepressants in patients with MDD
      and various anxiety disorders. All short-term RCTs of antidepressants in patients
      with MDD and various anxiety disorders were included. Individual patients' data
      were available for all trials. Data were available for the 207 trials conducted
      in patients with MDD, including a total of 40,028 patients. There were 21 cases
      of suicide in these patients. Forty-four trials were conducted in patients with
      various anxiety disorders, including a total of 10,972 patients. There were 2
      cases of suicide in these patients. Overall, at least 1 case of suicide occurred
      in 21 of the 251 trials. Sixteen of the suicides in MDD trials occurred in trials
      that had only an active control comparison group, and most of these (14 cases)
      were observed in the non-North American trials. In the placebo-controlled MDD
      trials, the rate ratios of suicide in the combined drug groups compared with
      placebo were 1.07 (0.1-63.4) and 0.5 (0.0-36.7) for the non-North American and
      North American trials, respectively. In the anxiety disorder studies, the overall
      rate ratio of suicide for the selective serotonin reuptake inhibitors compared
      with placebo was 0.9 (0.0-71.4). Neither use of placebo nor of antidepressants in
      short-term RCTs was associated with an increased risk of completed suicide among
      patients with MDD or various anxiety disorders. Nonetheless, because of the small
      numbers of suicides in these trials and the subsequent lack of statistical power,
      an increased risk of completed suicide in association with either drug or placebo
      treatment cannot be definitively excluded.

PMID- 16633154
TI  - Hypothyroidism induced by quetiapine: a case report.

PMID- 16633155
TI  - A comparison of effects of fluoxetine and nortriptyline on the symptoms of major
      depressive disorder.

PMID- 16633156
TI  - Low serum concentrations of paroxetine in CYP2D6 ultrarapid metabolizers.

PMID- 16633157
TI  - The association between cytochrome P450-2D6 genotype and prescription of
      antiparkinsonian drugs in hospitalized psychiatric patients using antipsychotics:
      a retrospective follow-up study.

PMID- 16633158
TI  - Treatment of neuroleptic-induced tardive dyskinesia with levetiracetam: a case
      series.

PMID- 16633159
TI  - A survey of antidepressant prescribing practices in major depression with
      comorbid attention-deficit hyperactivity disorder.

PMID- 16633160
TI  - Visual hallucinations from the addition of riluzole to memantine and bupropion.

PMID- 16633161
TI  - Comments on article by Mitte and associates: "A meta-analytic review of the
      efficacy of drug treatment in generalized anxiety disorder".

PMID- 16633163
TI  - The international family of surgery; journey around the world.

PMID- 16633164
TI  - The ISCFS: a body for clinical, educational, and research innovation.

PMID- 16633165
TI  - Evaluation of immediate phase of management of missile injuries affecting
      maxillofacial region in iraq.
AB  - In the past two years Iraq was, and still is, subjecting to a confluence of
      conventional war, civil unrest, guerrilla and terrorist attacks as well as an
      increasing crime rates. This study evaluates the immediate phase of management of
      100 patients suffering from missile injuries to the maxillofacial region.
      Patients were treated in the maxillofacial unit in the Specialized Surgeries
      Hospital Medical City, Baghdad during one year (from 2003 to 2004). We had 79 men
      and 21 women. Age ranged from three to 72 years (mean 37.5 years). The majority
      of injuries were caused by rifle bullets (49%) followed by fragments (29%),
      handgun bullets (15%), airgun pellets (6%), and shotgun (1%). Injuries consisted
      mainly of mandibular fractures found in 56 patients. Urgent airway management was
      needed in (27%) of patients. Nineteen patients were presented with active
      bleeding which would not stop without intervention. Most entrance and exit wounds
      as well as retained missiles were located in the cheek (54.8%, 39.4%, and 27.5%
      respectively). There were three mortalities due to complications related to head
      injury. Distribution of missiles used in any conflict reflects the type of this
      conflict, the prevailing local conditions, and the technological efficiency of
      weapons used by the opposing teams. Particularly challenging are missile injuries
      that involve the face, not only because of problems with reconstructing bone and
      soft tissue defects but also because of emergent problems with airway obstruction
      and neurovascular compromise.

PMID- 16633166
TI  - Post-traumatic reconstruction of the enucleated contracted eye socket: a
      comparative study.
AB  - Contracted eye socket is a constant cosmetic embarrassment to the patient. It
      does not only render patients unable to maintain eye prosthesis, but it becomes a
      source of chronic discharge and irritation. Traumatic injuries to the orbit and
      neighboring soft tissue lead to a contracted eye socket. To evaluate the use of
      full thickness and thick split thickness skin graft in the reconstruction of
      contracted eye socket with achieving satisfactory cosmetic results we used
      bilateral fish tail incision in continuity with the transverse incision on the
      back of the eye socket for rising of two unipedicle hinge flaps for creation of
      upper and lower fornices. Fixation of full-thickness and thick split-thickness
      skin graft to the created raw area by stitch and splint (non-adherent tulle and
      eye prosthesis).Twenty-six patients with contracted eye sockets treated with
      above method from February, 2004 to March, 2005. Eye sockets with adequate size
      were created in 22 patients and the results were satisfactory, four patients had
      unsatisfactory results due to partial loss of the full thickness skin graft. We
      believe that thick split thickness skin graft can be effectively used well than
      full thickness skin graft in the reconstruction of the contracted eye socket with
      uncomplicated problems.

PMID- 16633167
TI  - Apoptotic changes of Middle East jaw lymphoma.
AB  - Jaw lymphoma a highly malignant tumor affects children between two and eight
      years, duration of illness between two and three weeks, and the general condition
      of severe toxicity, and the death rate is 91.9%. The aim of this cellular study
      is to show the apoptotic changes associated with these tumors. Twenty-four
      children, 13 boys and 11 girls, were reported with jaw lymphoma and studied for
      apoptotic detection of the tumor through morphological assessment by using ground
      section and electron microscopy. Ground section shows lymphoblastic lymphoma,
      darkly-stained of ribonucleic acid, also apoptotic changes seen in some of the
      cells. Electron microscopy showed high mitotic figures, lymphoblast transformed
      to plasma cell, high nucleocytoplasmic ratio, some cells showed double nuclei,
      some nuclei are crested in shape or convoluted, degenerative changes seen in some
      of the cells, chromatin clumps near the nuclear membrane, mitochondria showing
      homogenous and degenerative changes, virus like particles seen in this nucleus
      and cytoplasm. The presence of low-level of apoptosis is a poor prognostic
      feature of jaw lymphoma due to homogeneity and degenerative changes of the
      mitochondria and disruption of the cell surface.

PMID- 16633168
TI  - Variable co-diagnosis of plagiocephaly and torticollis in Texas health care
      facilities.
AB  - Diagnosis of positional plagiocephaly has increased as babies have been put to
      sleep supine. The literature varies in reported co-incidence of
      sternocleidomastoid torticollis, as well as in definition of torticollis as a
      defect. Statewide data from the Texas Birth Defects registry was analyzed for the
      diagnosis of plagiocephaly with or without co-diagnosis of torticollis. There
      were 172 facilities with at least 1 diagnosis of plagiocephaly. Of these, 18
      facilities had recorded >20 cases and 3 facilities had recorded >150 cases. In
      the 18 facilities, percentage of plagiocephaly/torticollis co-diagnosis ranged
      from 5% to 67%. Two facilities specialize in orthopedic or neurologic problems,
      but the rest are general pediatric facilities. The three facilities with the most
      cases showed co-diagnosis of 10% (16 of 159 cases), 29% (108 of 376 cases), and
      54% (122 of 228 cases). It is noted that the three largest facilities use
      different professionals and different medical specialists in evaluation of cases.
      These data suggest that the wide range in torticollis diagnosis is less likely to
      reflect true patient variability than an inconsistently applied definition of the
      defect. Other factors that may play a role are diagnosis by non-MD medical
      professionals, involvement of different MD specialists in different facilities
      and diagnosis-dependent but variable insurance reimbursement.

PMID- 16633169
TI  - Application of the spanning plate concept to frontal orbital advancement:
      techniques and clinical experience in 60 patients.
AB  - Frontal orbital advancement (FOA), is the procedure of choice in treatment of
      coronal and metopic synostosis. Resorbable plates and screws have been widely
      accepted for use in pediatric craniofacial surgery, including FOA. We have
      applied the concept of extended resorbable spanning plates to FOA for metopic,
      unilateral, and bilateral coronal synostosis in infants and children during a 5
      year period. We report on 60 patients, ages 4 to 15 months (mean, 7 months); 28
      girls, 32 boys. Follow-up ranged from 12 to 36 months (mean, 24 months). There
      were no structural failures, no infections, and no complications related to the
      use of extended spanning plates. Extended spanning plates decrease mobility
      between bone segments, confer greater stability to the construct, and reduce both
      the number of plates and of screws that are necessary and reduce the operative
      time. Application of these plates simplifies FOA surgery and represents a step in
      the evolution of plating technology.

PMID- 16633170
TI  - Palpebral ptosis: clinical classification, differential diagnosis, and surgical
      guidelines: an overview.
AB  - Palpebral ptosis indicates the abnormal drooping of the upper lid, caused by
      partial or total reduction in levator muscle function. It may be caused by
      various pathologies, both congenital and acquired. Based on a review of the
      available literature and on our own clinical experience, a classification is
      proposed as well as a differential diagnosis between ptosis and pseudoptosis.
      Some basic surgical guidelines related to age of onset and etiopathogenesis are
      drawn. Ptosis is divided into neurogenic, myogenic, aponeurotic, and mechanical.
      The aim of surgery is two fold: functional, to correct the limit in the visual
      field; and also aesthetic. From January 2000 to January 2004, 42 patients were
      referred and treated at the Unit of Cranio-Maxillofacial Surgery-Centre for
      Orbital Pathology and Surgery, Hospital and University, Ferrara, Italy. Of these,
      12 cases were congenital and 30 acquired (13 were monolateral and 29 bilateral,
      for a total of 71 cases). The most widely used surgical techniques were levator
      muscle recession and frontalis suspension. In congenital forms, these techniques
      were often associated with techniques to correct oculo-muscular imbalance (i.e.,
      strabismus).Seventy-one upper eyelids were treated, 5 of which were mild, 35
      moderate, and 31 severe. Regarding levator muscle function, 60 were fair and 11
      poor.Surgical treatment followed the indications and timing with good morphologic
      and aesthetic results. Complications included two cases of hypocorrection, two
      asymmetries, and two cases of hypercorrection. Surgical treatment of palpebral
      ptosis is complex and requires precise diagnosis and indications for surgery
      related to clinical examination and pathogenesis. Even if these indications are
      strictly followed, in some cases, the outcomes are unpredictable.

PMID- 16633171
TI  - Long-term results after mandibular continuity resection in infancy: the role of
      autogenous rib grafts for mandibular restoration.
AB  - Reconstruction of mandibular defects after tumor resection in infants is a
      particular challenge. Although autogenous rib grafts have no relevance nowadays
      for restoration of mandibular bone defects after ablative tumor surgery because
      of limited bone stock and the availability of other donor areas, they are a
      useful surgical alternative after tumor surgery in infants. We here report on a 6
      month, 5-year, and 10-year follow-up of three children who were diagnosed with
      benign tumors of the mandible with osseous destruction at the ages of 4 months, 6
      months, and 2 years, respectively. Histologic diagnoses were melanotic
      neuroectodermal tumor, hemangioendothelioma of the mandible, and ameloblastoma.
      After continuity resection of the mandible, latero-mandibular bone defects were
      restored using autogenous rib grafts. Both clinical and radiologic follow-up
      visits in all children were performed to assess growth of the facial skeleton as
      well as the mandibular growth. Cephalometric measurements on Panorex films and
      three-dimensional computed tomographic scans revealed slight vertical growth
      excess and transversal growth inhibition of the reconstructed mandible in
      comparison with the nonoperated side. Although further growth of rib grafts is
      difficult to predict and occlusal disharmony may occur because of physiologic
      maxillary growth and growth of the unaffected mandible, we think that autogenous
      rib grafts can be ideally used for restoration of mandibular continuity defects
      in newborns and young children. Clinical follow-up visits on a yearly basis and
      orthodontic controls are useful for early orthodontic treatment of growth
      deficits. Further corrective surgery with bone augmentation or osseous
      distraction is required after completion of growth of the facial skeleton.

PMID- 16633172
TI  - Analysis of nasal bone fractures; a six-year study of 503 patients.
AB  - The aim of this study is to classify the nasal bone fractures based on computed
      tomography (CT) analysis and patterns of the nasal bone fractures, and review 503
      cases treated between 1998-2004 at the Department of Plastic Surgery, Inha
      University Hospital, Incheon, South Korea. The age, sex, etiology, associated
      injuries, pattern of fractures and treatments were reviewed and a radiographic
      study was analyzed. Plain simple radiographs of lateral and Waters view of the
      nasal bones combined with computed tomography scans were done. Nasal bone
      fractures were classified into six types: Type I) Simple without displacement;
      Type II) Simple with displacement/without telescoping; IIA; Unilateral; IIAs)
      Unilateral with septal fracture; IIB) Bilateral; IIBs) Bilateral with septal
      fracture; Type III) Comminuted with telescoping or depression. Diagnosis of nasal
      bone fractures were made positively by plain x-ray films in 82% of cases,
      negative finding was 9.5% and 8.5% of cases were suspicious of the fractures.
      Reliability of the plain film radiographs of the nasal bone fracture was 82% in
      this study. In the most of the fractured nasal bones (93%) the closed reduction
      was done, open reduction in 4% and no surgical intervention in 3%. Nasal
      reduction was carried out in average 6.5 days post the injury. The patterns of
      the nasal bones fractures classified by CT findings were type IIA (182 cases,
      36%), IIBs (105 cases, 21%), IIB (90 cases, 18%), IIAs (66 cases, 13%), I (39
      cases, 8%) and III (21 cases, 4.3%). We think the CT is necessary for diagnosing
      nasal bone fracture because the reliability of the plain film was only 82%.

PMID- 16633173
TI  - Multi-centric basal and squamous cell skin malignancies of the craniofacial
      region.
AB  - The etiology of skin malignancies is evaluated as multi-factorial. The human
      phenotype, syndromes, precursor lesions, and immunologic differences play as risk
      factors as well as environment. Twenty-seven patients with multi-centric skin
      malignancies investigated as if having predisposing syndromes. The etiological
      factors and the classification of skin malignancies are assessed. We last
      discussed about the management options. The mean age was 47 (9-91). Men to women
      ratio was 16:11. Four out of 27 patients having multi-centric skin malignancies
      were realized as syndromic. The localization of these tumors was entirely at the
      head and neck region. Ninety-eight areas were distinguished as having skin
      malignancies in 27 patients. Sixty-one incisional biopsies for type analysis and
      37 excisional biopsies were handled. Of the 98 malignancies, 24 were squamous
      cell cancer, 67 were basal cell cancer, and seven were basosquamous cell cancer
      pathologically. Wound closures were carried out as primarily in 39 excisions;
      using skin grafts in 21 excisions, local flaps in 28 excisions, and distant flap
      procedures in 10 regions. The follow-up period was between six and 25 months. No
      complications or recurrences were seen. Eight patients applied with new lesions
      on new regions, six patients had excision, and two were treated with
      radiotherapy.

PMID- 16633174
TI  - Tracheal cartilaginous sleeve with cricoid cartilage involvement in Pfeiffer
      syndrome.
AB  - Pfeiffer syndrome is one of a group of craniosynostosis syndromes in which rare
      tracheal anomalies have been described. This group of patients have a poor
      prognosis, and mortality can be related to airway complications and respiratory
      distress. We report a case of type II Pfeiffer syndrome with tracheal
      cartilaginous sleeve and cricoid cartilage involvement. We discuss our strategy
      for the management of the airway of this patient.

PMID- 16633175
TI  - Three-dimensional technology and bone morphogenetic protein in frontal bone
      reconstruction.
AB  - Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to
      facilitate healing of bony defects. The effect of different BMPs is, as with many
      other growth factors, highly dependent on the delivery vehicle. Bovine type I
      collagen is currently used in the clinical setting as a carrier and has been
      approved in several countries for human use. Here, we report the reconstruction
      of a frontal bone defect using heparin together with bovine type I collagen,
      hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created
      on the back of the patient by treating the latissimus dorsi muscle with the
      growth factor. A polyamide mold was used as a template to achieve the desired
      shape. The bone structure was transplanted into the defect site via microsurgical
      techniques. Although the prefabricated bone was not large enough tocover the
      entire frontal defect, the reconstruction was completed by using an additional
      cranial implant.

PMID- 16633176
TI  - The anatomic landmarks of ethmoidal arteries for the surgical approaches.
AB  - Knowledge of variations in the possible patterns of origins, courses, and
      distributions of the ethmoidal arteries are necessary for the diagnosis and
      important for the treatment of orbital disorders. Ethmoidal arteries are damaged
      in endonasal surgical interventions and in operations performed on the inner wall
      of the orbita.A description of the anatomic landmarks of the ethmoidal arteries
      and ethmoidal canals is presented, based on data from microdissection in 19 adult
      cadavers studied after injection of red-dyed latex into the arterial bed. In all
      subjects, each of ethmoidal arteries originated from ophthalmic artery. The
      anterior ethmoidal artery was observed in all specimens except for one case. The
      diameter of the artery thicker than the posterior ethmoidal artery was 0.92 +/-
      0.2 mm on the right and 0.88 +/- 0.15 mm on the left. The branching of the
      anterior ethmoidal artery from the ophthalmic artery was determined in four
      different types. The diameter of the posterior ethmoidal artery was measured as
      0.66 +/- 0.21 mm on the right and 0.63 +/- 0.19 mm on the left. The anterior
      ethmoidal canal was located between the second and third lamella in 29 of 38
      cases. The mean distance between the limen nasi and anterior ethmoidal canal was
      48.1 +/- 3.2 mm.The article confirms the well-known variability of the ethmoidal
      arteries and their topographic relation to the ethmoidal canals. Advances in
      surgical techniques, instrumentation, and regional arterial anatomy have resulted
      in functional operations of endoscopic sinus and orbital surgery with fewer
      complications.

PMID- 16633177
TI  - Relationship between depressor septi nasi muscle and dermocartilagenous ligament;
      anatomic study and clinical application.
AB  - The aim of this study is to elucidate the anatomical and functional relationship
      between dermocartilagenous ligament and depressor septi nasi muscle. The noses of
      four Korean adult cadavers were studied and total of 123 patients (96 women, 27
      men) were operated. The Depressor septi nasi muscle inserted to the base and
      lateral surface of the medial crus of lower alar cartilage. Dermocartilagenous
      ligament extended posteriorly and met depressor septi nasi muscle. It was pulled
      downward by the depressor septi nasi muscle. In all 123 cases the nasal tips were
      elevated after the dermocartilagenous ligaments were severed. Nasolabial angles
      increased from 5 - 15 degrees and the noses were shortened. Our morphological
      study and clinical experience suggest strongly the dermocatilagenous ligament was
      pulled downward by the depressor septi nasal muscle. We believe the
      dermocatilagenous ligament acts as a depressor.

PMID- 16633178
TI  - Usefulness of simultaneous pre-maxillary osteotomy and bone grafting in the
      bilateral clefts.
AB  - Bilateral cleft lip and palate patients sometimes accompany with mal-positioned
      premaxilla, which adversely affect the upper lip morphology, especially widened
      naso-labial angle as well as functional deteriorations such as speech impairment
      though the fistula in between the alveolar segments. Usefulness of simultaneous
      premaxillary osteotomy and bone grafting was tested in respect of grafted bone
      resorption rate and required bone volume. Between January, 2001 and December,
      2003, seven patients (seven years and eight months to 16 years old; average 9.7
      +/- 2.87, 2 females and 5 males) with complete bilateral cleft lip and palate
      patients were performed the simultaneous premaxillary osteotomy and bone
      grafting, whereas in the same period of between January, 2001 and December, 2003,
      four patients (seven years and 11 months to 11 years old; average 9.2 +/- 1.01, 4
      female and 6 males) with complete bilateral alveolus in order to compare
      cancellous bone volumes to relatively milder and less-protruded premaxilla. The
      bone grafting was performed in two-stage manner as one side and later, the other
      side. The bone volume required for cleft packing was significantly lower in
      osteotomized cases compared to those of non-osteotomized (3.5 +/- 0.69 mL vs. 5.6
      +/- 0.70 mL, P < 0.01). There were twenty for non-osteotomized cases (10
      bilateral clefts) and fourteen osteotomized (7 bilateral clefts) were evaluated.
      Overall, majority of both groups demonstrated the grade I (10/20 for non
      osteotomized, 12/14 for osteotomized group). There was significant lower bone
      resorption rate in osteotomized group compared to the non-osteotomized group (1.1
      +/- 0.36, 1.7 +/- 0.75, osteotimized, non-osteotomized, respectively, P < 0.05).
      The simultaneous premaxillary osteotomy and bone grafting is beneficial over
      staged bone grafting in bilateral cleft cases in requiring bone chio volume and
      subsequent bone resorption rate. The meticulous dissection and re-location of the
      premaxilla improves the overall lip morphology.

PMID- 16633179
TI  - Repair of bone defects treated with autogenous bone graft and low-power laser.
AB  - Because bone healing at the graft site is similar to a fracture repair, the
      purpose of the present study was to evaluate the effects of low-power laser
      irradiation on the repair of rat skull defects treated with autogenous bone
      graft. A defect measuring 3 mm in diameter was produced in the left parietal bone
      and filled with an autogenous bone graft obtained from the right parietal bone.
      The animals were divided into 3 groups of 20 rats each: nonirradiated control,
      irradiated with 5.1 J/cm, and irradiated with 10.2 J/cm. The laser (2.4 mW, 735
      nm, 3.4 x 10 W/cm, 3-mm spot size) was applied three times per week for 4 weeks.
      Greater volume of newly formed bone was observed in the irradiated group with
      10.2 J/cm. In both irradiated groups, a greater volume of newly formed bone
      occurred only in the first 2 weeks. The results demonstrated that laser
      irradiation at the grafted site stimulated osteogenesis during the initial stages
      of the healing process in a skull defect of the rat and that this effect was dose
      dependent.

PMID- 16633180
TI  - Polymer-based biodegradable drug delivery systems in pain management.
AB  - Pain is an unpleasant sensory experience commonly produced by damage to bodily
      tissues and it is one of the most significant public health problems, because
      21.5% of the world population is estimated to suffer from pain. It results in a
      total loss of more than 165 billion US dollars each year in the United States
      alone. Pain reflects a mixture of various pathophysiologic, psychologic, and
      genetic contributions. When undertreated, pain usually results in serious immune
      and metabolic upset. Therefore, it requires wide understanding and intensive
      effort for a better management. Currently, pain control is limited by the modest
      efficiency of the used drugs, the serious side effects of these drugs, and the
      inefficacy of conventional drug administration. By the introduction of the
      technology of biodegradable controlled-release devices into clinical practice,
      pain control not only benefits from these novel methods for a better delivery of
      various drugs, but the side effects of the drugs are reduced because use of the
      devices improves patient compliance. Biodegradable controlled-release devices are
      polymer-based devices that are designed to deliver drugs locally in a predesigned
      manner. Recently, there was a high interest in developing these devices for the
      delivery of different drugs used for pain control. This paper first highlights
      the dimensions and basics of the problem of pain. Then, it presents an overview
      of the biodegradable polymers that are used in drug delivery systems and
      summarizes the studies carried out on these systems in the field of pain
      management. We refer to our experience in developing a device for multimodal drug
      delivery, including the use of nanotechnology. Future perspectives are also
      presented.

PMID- 16633181
TI  - A new method of 3-D cephalometry Part I: the anatomic Cartesian 3-D reference
      system.
AB  - The purpose of this study was to present a new innovative three-dimensional (3-D)
      cephalometric method. Part I deals with the set-up and validation of a voxel
      based semi-automatic 3-D cephalometric reference system. The CT data (DICOM 3.0
      files) of 20 control patients with normal skeletal relationships were used for
      this study. To investigate accuracy and reliability of the 3-D cephalometric
      reference system (Maxilimtrade mark, version 1.3.0) a total of 42 (14 horizontal,
      14 vertical and 14 transversal) orthogonal measurements were performed on each
      patient twice by each of two investigators. The intra-observer measurement error
      was less then 0.88 mm, 0.76 mm and 0.84 mm for horizontal, vertical and
      transversal orthogonal measurements, respectively. The inter-observer measurement
      error was less as 0.78 mm, 0.86 mm and 1.26 mm for horizontal, vertical and
      transversal orthogonal measurements, respectively. Squared correlation
      coefficients showed a high intra-observer and inter-observer reliability. The
      presented 3-D cephalometric reference system proved to be accurate and reliable
      and can therefore be used for 3-D cephalometric hard and soft tissue analysis.

PMID- 16633182
TI  - Relation between intracranial volume and the surface area of the foramen magnum.
AB  - Several investigators have estimated the intracranial volume (ICV) in the past
      which indirectly reflects the brain volume. Most of these studies have been made
      on the dry skulls using linear dimensions, packing methods or occasionally
      radiological methods. It is also reported that the etiology of cerebellar
      tonsillar herniation is closely related to the size of the foramen magnum (FM).
      In the present study the ICVs have been estimated in 28 dry skulls using filling
      water method and the surface area of FMs were measured planimetry method. The
      estimated mean ICV was 1,311 +/- 133 cm. Surface area of FM was 760 +/- 144 mm.
      Antero-posterior and lateral direct roentgenograms of the skulls were also taken
      and the width, height and length (WHL) of the skull were measured by means of the
      cephalometry on radiograms. The relationship between the ICV, WHL and surface
      area of FM were analyzed statistically. The ICV, WHL and surface area of FM was
      correlated well (r = 0.271, P < 0.005; r = 0.265, P < 0.005, respectively) and a
      regression formula was proposed. Our results showed that skulls with larger ICV
      and WHL have larger FM surface area. We also suggested a regression formula that
      could be used to predict the surface area of FM regarding to the ICV and WHL
      values. In the next step, we took roentgenograms of skulls and obtain ICV
      measuring the width, length and height of skulls by means of cephalometry and
      investigate the relation between the findings of cephalometry and surface area of
      FM. The cephalometry could apply on living subjects and, thereby, our findings
      could provide some data to evaluate the etiology of Arnold Chiari malformation
      and achondroplasia for living subjects.

PMID- 16633183
TI  - Stability of craniofacial PLLA/PGA copolymer bioabsorbable screws.
AB  - The behavior of bioabsorbable plates and screws after implantation is a dynamic
      process that results in dimensional changes of the devices after surgery.
      Bioabsorbable plates frequently are recognized as changing because of their size,
      but bioabsorbable screws are less appreciated in this regard. How bioabsorbable
      screws may change after placement and whether their manufacturing method has an
      influence on size and shape after implantation needs further study. Using 1.5-mm
      diameter screws made of an oriented copolymer of 82% poly-L-lactic acid and 18%
      polyglycolic acid (LactoSorb copolymer), screw dimensions were measured before
      and after soaking in an in vitro pH 7.4, 37 degrees C buffer environment. After
      33 days of exposure to buffer, there were no changes in the physical appearance
      of the screws, and there was no change in dimensions or shape. The orientation of
      polymer materials in a bioabsorbable screw device improves its strength and can
      retard the rate of hydrolysis. However, the residual stresses in oriented screws
      theoretically can potentiate dimensional shift in the implants during hydrolysis.
      That such shift did not occur during the early phase of hydrolysis provides
      further evidence of the mechanism by which these types of screws can maintain
      biomechanical function throughout the bone-healing phase of the craniofacial
      skeleton.

PMID- 16633184
TI  - Feasibility of transcutaneous mandibular distraction using an internal device.

PMID- 16633185
TI  - Primary and revision cleft lip repairs using octyl-2-cyanoacrylate.
AB  - The purpose of our retrospective review is to examine our method and outcomes for
      the application of octyl-2-cyanoacrylate for the repair of primary and revision
      cleft lips in both pediatric and adult patients. Records and photographs were
      reviewed and analyzed for patient age, type of cleft, revision or primary repair,
      complications, length of follow-up, and aesthetic outcomes. Eighteen patients,
      both children and adults, who underwent cleft lip repairs using tissue adhesive
      performed by a single surgeon between 1999 and 2003 were included. Twelve
      patients underwent primary repair and 6 patients underwent revision repair.
      Repairs were performed using the Millard rotation advancement technique and the
      Mohler variant. The lateral advancement flap was kept long and redundant in its
      transverse dimension to create a pressure fit everting the skin edges with
      minimal sutures to set up the closure for application of the tissue adhesive.
      Seventeen of eighteen patients had excellent cosmetic outcomes. One patient had
      minor necrosis of the tip of the advancement flap. No allergic reactions, wound
      infections, or dehiscences occurred. The use of octyl-2-cyanoacrylate for the
      skin closure of primary and revision cleft lip repairs in both children and
      adults results in excellent cosmetic outcomes. Employing our pressure-fit
      technique for skin eversion prior to application of the tissue adhesive may be
      advantageous. The lack of suture removal in the pediatric population and
      decreased operative time are additional benefits.

PMID- 16633186
TI  - Automatic hole repairing for cranioplasty using Bezier surface approximation.
AB  - Cranioplasty is the procedure that repairs holes or defects in the skull with
      cranial implants. When the bone from the hole is missing, damaged, or infected,
      the defect needs to be covered with an artificial plate to protect the brain. In
      this paper, a hole-repairing algorithm is developed to aid in shaping artificial
      plates for Cranioplasty, by describing a method for filling holes in defective
      biomodels with unstructured triangular surface meshes or in stereo-lithography
      format. The resulting patching meshes interpolate the shape and density of the
      surrounding mesh. The steps in repairing a hole include hole identification, hole
      triangulations using Genetic Algorithm optimization, and a customized advancing
      front meshing technique using surface approximations based on a Quartic Bezier
      patch/surface.

PMID- 16633187
TI  - Correction of the frontoethmoidal encephalomeningocele with minimal facial
      incision: modified Chula technique.
AB  - BACKGROUND: At present all surgical techniques to correct the frontoethmoidal
      encephalomeningocele require extensive incisions over the mass and perinasal
      area, thus adding scars to the already-disfigured faces. This study demonstrates
      a possibility of doing definitive surgery with minimal facial incision. METHODS:
      The technique follows the principles of the "Chula technique," which is the one
      stage definitive technique without formal frontal craniotomy. However facial
      incision was kept to minimum, or even avoided, while amputation of the
      herniation, dural repair, skull defect closure, and repositioning of the medial
      canthal ligaments were performed mainly via the coronal incision. RESULTS: There
      were 20 patients operated on using this modified Chula technique. No perinasal
      incision was needed at all in three patients (15%) with F1 masses (small- and
      medium-sized masses according to the "FEEM classification"). Three patients with
      F1 masses had only small stab incisions just medial to the medial canthus for
      medial canthopexy. The rest (70%) consisting of two F2 (large-sized) masses and
      twelve F1 masses had limited nasal incisions just to help removing the facial
      masses and correcting facial deformity. With an average of 287 days of follow-up
      period (14-997 days), there had been no cerebrospinal fluid leakage or disease
      recurrence. CONCLUSIONS: Correction of the frontoethmoidal encephalomeningocele
      can be done safely via the coronal incision alone while facial incision can be
      omitted or, if necessary, kept to minimum.

PMID- 16633188
TI  - The role of trans-oral digital pressure in the removal of large dumbbell shaped
      tumor from deep lobe of parotid gland.
AB  - A 44-year-old male patient, a cardiothoracic surgeon by profession, presented
      with a tumor arising from the deep lobe of the right parotid gland.
      Investigations confirmed its para-pharyngeal location and its dumbbell shape. A
      total conservative parotidectomy was performed preserving full function of the
      facial nerve. The case is presented because of the unique technique used for this
      procedure.

PMID- 16633189
TI  - Squamous cell carcinoma of the auricle arising from keloid after radium needle
      therapy.
AB  - The squamous cell carcinoma (SCC) of the auricle was one of the common tumors of
      not only skin but also ear. SCC of the auricle was described to be the carcinoma
      of old age with some predisposing factors and keloid was known to be one of the
      predisposing factors for malignant tumors. Keloid and radium needle therapy were
      risk factors, latter the major, independently from each other and were reported
      to conclude in SCC depending on the duration for the keloid and the dose for the
      radium needle therapy. The increased age with the long duration of these
      predisposing factors should have to be kept in mind in every situation when these
      treatment modalities had been planned to. Surgical interventions should always be
      the first choice in the treatment of not only the carcinomas but also in keloids
      in selected cases.

PMID- 16633190
TI  - Surgical treatment of amalgam fillings causing iatrogenic sinusitis.
AB  - Iatrogenic maxillary sinusitis is a rare disease entity that can be fatal if not
      managed. Thirteen patients (five men and eight women) were referred to our clinic
      because of chronic iatrogenic maxillary sinusitis. Eight patients presented with
      a left-side maxillary sinusitis, four patients presented with right-side
      maxillary sinusitis, and one patient presented with right-side pan sinusitis. The
      sinusitis was caused by the intrusion of amalgam filling during root treatment of
      teeth. All of the patients were treated surgically with a Caldwell-Luc approach.
      In 12 patients, the amalgam was removed with the infected and inflamed maxillary
      mucosa. In one patient, the amalgam could not be removed with the Caldwell-Luc
      technique because it was in the deeper part of the root of the molar tooth.
      Histologic examination revealed four cases of aspergillosis; three cases of
      papillary and polypoid sinusitis; three cases of nonspecific pseudo-polypoid
      sinusitis; two cases of hyperplasic polypoid sinusitis; and one case of catarrhal
      sinusitis. All patients were relieved of their complaints that were related to
      sinusitis. Radiologically, the maxillary sinuses were clean 1 month after
      Caldwell-Luc intervention. Iatrogenic maxillary sinusitis should be considered a
      serious infection. A smear should be taken whenever a foreign body is intruded
      into the sinus. Foreign bodies can get jammed in the posterior wall of the sinus
      and can provoke chronic sinusitis with a risk intracranial extension. Hence, the
      disease should be managed surgically without delay. Furthermore, dentists should
      be cautious with dental amalgam filling.

PMID- 16633191
TI  - Pindborg tumor in children.
AB  - Pindborg tumor or calcifying epithelial odontogenic tumor is a rare benign
      neoplasm. The average age at diagnosis is 40 years without a significant
      prevalence for one sex. The most frequent localization is the mandibular premolar
      and molar area; less frequently the lesion is found in the maxilla, while other
      localizations like the maxillary sinus are extremely rare. Ethiology of this
      lesion is not clear. The complete surgical removal of the lesion is usually
      considered the most common type of treatment. The authors report a peculiar case
      of Pindborg tumor characterized by a rare localization of the lesion (maxillary
      incisal area) and by the young age of the patient (nine years old). The correct
      treatment in the case of a small mass is the surgical enucleation of the lesion.
      The purpose of the surgical treatment is the radical resection of the neoplasm
      with clean margins in order to reduce the risk of recurrence of disease.
      Recurrence of disease many years after surgical therapy has been reported that is
      why a clinical and instrumental long-term follow-up of the patient are suggested.

PMID- 16633192
TI  - Treatment of macroglossia in Beckwith-Wiedemann syndrome.
AB  - A case of macroglossia caused by Beckwith Wiedemann syndrome is reported.
      Beckwith-Wiedemann Syndrome is an overgrowth disorder characterized by a
      constellation of congenital anomalies. The most common manifestations are
      omphalocele, macroglossia, gigantism, and visceromegaly. When the tongue reaches
      a huge dimension, clinical symptoms are represented by dysphagia, alterations in
      speech, difficulty in chewing, obstruction of the upper airways, and psychologic
      consequences derived from the patient's physical appearance. The authors describe
      the surgical strategy performed in the reported case.

PMID- 16633193
TI  - Perforating pilomatricoma on the upper eyelid.
AB  - We report a rare case of perforating pilomatricoma. A 50 x 40-mm oval nodule,
      with a whitish scale on its tip, developed on the left upper eyelid of a 43-year
      old Japanese woman. There was no history of injury to the left upper eyelid.
      Histologic examination revealed typical microscopic features of pilomatricoma. In
      addition, however, an interesting phenomenon was observed: a portion of the tumor
      mass had extruded from the upper dermis to the skin surface through a perforating
      epidermal channel in the middle of the tumor. These findings are consistent with
      the diagnosis of perforating pilomatricoma.

PMID- 16633194
TI  - Temporomandibular disorders due to improper surgical treatment of mandibular
      fracture: clinical report.
AB  - A case of mandibular fracture surgically consolidated in a wrong position
      resulting in craniomandibular disorders is reported. The inadequate surgical
      alignment of the healed bony segments caused a malocclusion. This changed the
      original neuromuscular system such that compensatory mechanisms began to change
      the whole balance of the organism. The patient presented a mandibular crossbite,
      an asymmetry of the face, and extensive alteration of muscular, articular, and
      postural function. The bony malunion and malocclusion were treated using an
      interdisciplinary surgical-orthodontic treatment for correcting functional
      disorders and aesthetic deformity. Electromyography and computerized mandibular
      scanning were used to evaluate improvement of the muscular activity, during rest
      and function, and of the mandibular kinesiology. Timing of surgical treatment and
      adequate fixation and immobilization of fracture segments are very important to
      avoid complications such as infection, delayed union, nonunion, malunion,
      skeletal discrepancies, nerve injury, and (rarely) ankylosis. The surgical
      approach should be based on the general criteria of traumatologic therapy,
      restoring the original bone shape and the right occlusal relations as soon as
      possible.

PMID- 16633195
TI  - Reconstruction of long cervical esophageal defects with the radial forearm flap.
AB  - The radial forearm flap has been used for reconstruction of the cervical
      esophagus most often as a patch or for circumferential repair of short defects
      (less than 5 cm). In the following three cases, the radial forearm flap was used
      to reconstruct circumferential cervical esophageal defects ranging from 5 to 12
      mm in length. These procedures were successfully carried out in three patients in
      whom the intraoperative defect was unexpectedly large or the intra-abdominal
      viscera harvest would have been difficult. These patients had reliable esophageal
      function 8 to 24 months after surgery. We conclude that the radial forearm flap
      can be used for reconstruction of large circumferential defects of the cervical
      esophagus.

PMID- 16633196
TI  - Distraction osteogenesis in a patient with juvenile arthritis.
AB  - We present a 26-year-old patient with juvenile-onset arthritis, Alagille's
      syndrome, micrognathia, and progressive sleep apnea. Despite the presence of
      significant temporomandibular joint pathology, mandibular distraction was
      indicated to correct life-threatening sleep apnea. Before distraction, the
      patient had only 10 mm of maximal interincisal opening and bilateral
      temporomandibular joint symptomatology. After distraction, the patient's sleep
      apnea resolved. There was slight improvement in her maximal incisal opening (12
      mm) with neither exacerbation nor improvement of her temporomandibular joint
      symptomatology.

PMID- 16633197
TI  - Late subperiosteal hematomata associated with craniofacial surgery.
AB  - Hematomata are well-recognized complications of surgery. Subperiosteal hematomata
      occur rarely and have not been well documented after craniofacial surgery. It is
      possible that craniofacial surgery increases the likelihood of subperiosteal
      hematomata occurring after minor trauma, even long after surgery, with a risk of
      subsequent ossification. Over a period of 7 years, 12 patients were identified as
      having possible subperiosteal hematomata. A number of these patients displayed
      distinct ossification in the area of the subperiosteal hematoma, resulting in an
      obvious contour defect. This can be prevented if the patients present early
      enough and if the hematoma is evacuated. Prompt evacuation of the hematoma is
      therefore suggested in any case with a history suggestive of a subperiosteal
      hematoma.

PMID- 16633199
TI  - ECT for treatment-resistant schizophrenia: a response from the far East to the
      UK. NICE report.
AB  - BACKGROUND: There is controversy about the proper place of electroconvulsive
      therapy (ECT) in the management of the schizophrenic patient, and the important
      issues related to theory and practice remain to be resolved, especially in the
      context of medication-resistant schizophrenia. METHOD: We briefly summarize
      existing research in the field. We next use a narrative method to describe in a
      single article the large body of research from Thailand that, during the past
      decade, has systematically studied issues related to the use of ECT in medication
      resistant schizophrenia. We integrate the findings of the Thai efforts with the
      results of other research and consider the theoretical and practical importance
      of the reviewed work. RESULTS: The ECT treatment data validate a BRPS cutoff of
      25 as a definition of recovery in patients with treatment-refractory
      schizophrenia, and a cutoff of 37 as a definition of subsequent relapse or
      suitability for entry into a treatment protocol. A 3-week post-ECT stabilization
      period identifies patients who maintain improvement and who can be legitimately
      considered to have sustained response to ECT. Clinical characteristics of such
      responders and symptoms responsive to ECT are described. Higher stimulus dose
      hastens response to ECT but does not improve responsiveness. Continuation ECT (C
      ECT) combined with maintenance-neuroleptic medication is associated with better
      treatment outcome than either treatment alone. The combined treatment also
      improves quality of life and functioning in the long-term. CONCLUSIONS: These
      findings convey several useful thoughts for research into and the practice of ECT
      for schizophrenia.

PMID- 16633200
TI  - Continuation and maintenance electroconvulsive therapy for the treatment of
      depressive illness: a response to the National Institute for Clinical Excellence
      report.
AB  - Continuation and maintenance electroconvulsive therapy (ECT) is used to prevent
      relapse and recurrence of depressive episodes in those patients who have failed
      previous continuation and/or maintenance pharmacotherapy and who have also
      responded to an acute course of ECT. These patients frequently have histories of
      medication-resistant depression, medication intolerance, and/or comorbid medical
      conditions that complicate the management of their psychiatric illness. Previous
      studies of continuation and maintenance ECT, mostly consisting of case reports
      and retrospective chart reviews, as well as several prospective studies, support
      the practice of continuation and maintenance ECT as a viable treatment option for
      these difficult-to-treat patients. However, continuation and maintenance ECT have
      come under fire recently because of concerns of insufficient controlled studies
      demonstrating its efficacy, its long-term benefits, and its risks. This article
      thus reviews the most recent data available on the use of continuation and
      maintenance ECT in the treatment of depressive disorders. Although few new
      prospective controlled studies exist in the literature, published and emerging
      data continue to support the use of continuation and maintenance ECT,
      particularly in those individuals with medication-refractory, ECT-responsive, and
      relapse-prone depression.

PMID- 16633201
TI  - Health-related quality of life and the practice of electroconvulsive therapy.
AB  - In the past several decades, health-related quality of life (HRQL) measures have
      become increasingly important as a type of patient-reported outcome documenting
      the subjective psychosocial burden associated with chronic illness. This article
      provides an introduction to HRQL, summarizes the measurement of HRQL in major
      depression and bipolar disorder, and reviews electroconvulsive therapy (ECT)
      studies that have measured HRQL. Health-related quality-of-life definitions and
      instruments vary widely but have nonetheless proven useful for evaluating the
      effects of disease and its treatment. Psychiatric disorders profoundly affect
      HRQL and, in many cases, exceed or contribute to the disease burden imposed by
      serious physical illness. An emerging literature demonstrates the importance of
      ECT in restoring function and HRQL in depressed patients. To keep pace as
      medicine is transformed along the dimensions outlined by the Institute of
      Medicine's Quality Chasm framework, ECT research must provide evidence supporting
      its safety and effectiveness and also that the treatment is patient-centered. A
      research agenda to demonstrate the subjective benefits of ECT must be mirrored by
      a practice of ECT that is increasingly customized to patient needs and values.

PMID- 16633202
TI  - Is ECT cost-effective? A critique of the National Institute of Health and
      Clinical Excellence's report on the economic analysis of ECT.
AB  - The report of the National Institute of Health and Clinical Excellence (NICE) on
      the economic analysis of electroconvulsive therapy (ECT) concludes that ECT and
      pharmacotherapy are "likely to be equally cost-effective" in the treatment of
      major depression. However, this economic analysis is acknowledged by the NICE
      report to be "crude and based on a number of uncertain assumptions." An
      evaluation by the Health Technology Assessment Committee of the National
      Coordinating Centre for Health Technology Assessment, commissioned and funded on
      behalf of NICE, provides a detailed cost comparison of ECT and pharmacotherapy in
      the treatment of major depression [Greenhalgh, Health Technol Assess, 9 (9)
      (2005) 1-156]. The Health Technology Assessment Committee analyzed data from
      separate studies of the efficacy of antidepressants and ECT. However, these data
      included few randomized controlled trials directly comparing the cost
      effectiveness of ECT and medication in treatment-resistant depression. In the
      limited number of trials included in the report, there was a bias in favor of
      medication. For example, compared with the antidepressant trials, the ECT trials
      included more patients who had comorbid psychosis and treatment-resistant
      depression and would therefore have a more difficult treatment of depression. The
      Committee also evaluated data to determine that the relapse rate after
      pharmacological treatment is approximately 3 times the relapse rate after ECT.
      Although the report provides a format for analyzing the cost-effectiveness of ECT
      and recommends future directions for research, the conclusions reached by the
      Committee are relatively limited and should not be used as a template for future
      public policy.

PMID- 16633203
TI  - Challenges to British practice of electroconvulsive therapy.

PMID- 16633204
TI  - What predicts patients' expressed likelihood of choosing electroconvulsive
      therapy as a future treatment option?
AB  - OBJECTIVE: To examine the relationship between stated intention to choose
      electroconvulsive therapy (ECT) as a future treatment option and measures of
      function and quality of life, mood, and cognition in the month after this
      therapy. Understanding the factors influencing patient choice of ECT is a source
      of insight into the interplay between measures of response and perceived value of
      this treatment to patients, lending perspective to patient-centered quality
      improvement efforts. METHOD: In a prospective sample of 77 depressed patients
      given ECT, we surveyed recipients at 1 month about their expressed likelihood of
      choosing ECT given a future episode and examined predictors of their responses.
      RESULTS: Thirty-four subjects were classified as "likely" to choose a course of
      ECT, whereas 33 patients were "unlikely." A model including Hamilton baseline and
      change scores as well as baseline scores in instrumental activities of daily
      living significantly predicted likeliness after controlling for age and sex (R =
      0.34, P < 0.0001). Other quality-of-life variables and measures of change in
      cognition were not significant in the model. CONCLUSIONS: In our sample, choosing
      ECT as a future treatment option was more likely for those who were more
      depressed before treatment, had more impaired instrumental activities at the
      outset of treatment, and experienced a more robust improvement in depressive
      symptoms. This variance was not explained by treatment-associated improvements in
      quality of life, function, or deficits in cognitive status.

PMID- 16633205
TI  - Electroconvulsive therapy in first-episode schizophrenia.
AB  - Knowledge about the efficacy of electroconvulsive therapy (ECT) on schizophrenia
      comes from chronic patients and little known on young, first-episode patients.
      The aim of this study is to evaluate short-term and long-term efficacy of ECT in
      patients with first-episode schizophrenia. In the first phase of the study, 90
      hospitalized, first-episode patients with schizophrenia were enrolled;
      psychopathology was evaluated with Brief Psychiatric Research Scale (BPRS), Scale
      for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of
      Negative Symptoms (SANS) on admission and discharge. Antipsychotics were first
      line treatment for most of the patients, but medication for nonrespondent
      catatonic patients and patients who had violent behaviors were treated with ECT.
      The patients who met the remission criteria were intended to a 1-year follow-up
      after discharge. BPRS, SAPS, and SANS were monthly recorded during the follow-up.
      Differences in clinical characteristics, relapse, and rehospitalization rates
      were analyzed in patients with or without ECT treatment. Thirteen patients were
      treated with ECT. They were low educated and were more likely nonparanoid
      subtypes (catatonic, disorganized). The ECT group had higher BPRS scores on
      admission and their hospitalization period was longer than the antipsychotic
      group. On the contrary, BPRS and SAPS scores of the ECT group were lower at
      discharge. The ECT group presented shorter follow-up duration than the
      antipsychotic group during the follow-up period. In conclusion, the efficacy of
      ECT was very satisfactory in acute term in first-episode schizophrenia, but the
      same efficacy was not continuous during the 1-year follow-up.

PMID- 16633206
TI  - Clinical outcome and memory function with maintenance electroconvulsive therapy:
      a retrospective study.
AB  - Although maintenance electroconvulsive therapy (ECT) appears to be the logical
      choice for the prevention of relapses and recurrences in patients with refractory
      depression who have responded to a course of ECT, the perception of ECT's
      negative effect on memory continues to limit its wider use. This retrospective
      study of depressed patients maintained on ECT after an initial course revealed
      that maintenance ECT was effective in sustaining clinical improvement,
      particularly in patients who showed a satisfactory clinical response to the
      initial course of ECT, and that memory difficulties were limited and tolerable.

PMID- 16633207
TI  - Nonconvulsive seizures in electroconvulsive therapy: further evidence of
      differential neurophysiological aspects of bitemporal versus bifrontal electrode
      placement.
AB  - In recent years, attention has been focused on the role of electrode placement in
      determining efficacy and cognitive side effects of electroconvulsive therapy
      (ECT). In particular, interest in bifrontal electrode placement has increased.
      Some evidence indicates differential therapeutic, cognitive, and
      neurophysiological aspects of bifrontal versus bitemporal ECT. Occasionally in
      ECT practice, electroencephalographic seizure activity is manifested in the
      absence of motor convulsive activity, a phenomenon termed nonconvulsive seizures.
      This probably indicates isolated prefrontal seizure activity in the absence of
      motor strip involvement. We reviewed our records and found that bifrontally
      treated patients had a significantly higher incidence of nonconvulsive seizures
      in ECT than did bitemporally treated patients. Seizure threshold was also higher
      among the bifrontal patients. We hypothesize that this provides further evidence
      of differential neurophysiology of seizures induced with these 2 electrode
      placements.

PMID- 16633208
TI  - Tolerability and safety of high daily doses of repetitive transcranial magnetic
      stimulation in healthy young men.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is an experimental technology
      that involves a powerful magnetic pulse applied to the scalp, which is sufficient
      to cause neuronal depolarization. Transcranial magnetic stimulation has been used
      in treatment studies for psychiatric disorders, primarily unipolar depression,
      and as a tool to map brain function. Although thousands of rTMS sessions have
      been given with few side effects, rTMS can produce serious adverse effects such
      as an unintended seizure. Safety guidelines for frequency, duration, and
      intensity of rTMS have aided in the prevention of such adverse side effects.
      However, the total dose (number of stimuli) able to be delivered safely to human
      subjects within a day or within a week has not been established. For example,
      previous rTMS studies as a treatment for depression consisted of delivering 800
      to 3,000 magnetic pulses per day, with 8000 to 30,000 magnetic pulses over 2 to 3
      weeks. This study examined whether high doses of rTMS within a day or over a week
      would produce significant side effects. As part of a study to examine rTMS
      effects in sleep deprivation, we exposed healthy men to 12,960 magnetic pulses a
      day for up to 3 days in 1 week. This equals 38,880 magnetic pulses over 1 week,
      which is likely one of the largest exposures of TMS to date. Despite this intense
      treatment regimen, we failed to produce significant side effects. Doses of up to
      12,960 pulses per day appear safe and tolerable in healthy young men.

PMID- 16633209
TI  - Electroconvulsive therapy stimulus dose expressed as volume of seizure foci.
AB  - BACKGROUND: Electrical stimulus dose is typically stated as charge in
      millicoulombs (mC), representing the number of electrons. However, by overlooking
      the voltage threshold for neuronal depolarization, charge alone is inappropriate.
      Any charge can accumulate from subthreshold voltage over time. Stimulus energy
      represents heat content; without a delivery rate, it is not related to
      depolarization voltage. The objective was to formulate stimulus dose in
      accordance with seizure induction physiology. METHOD: Stimulus dose was expressed
      as volume of generated seizure foci, a variable dependent on current and charge.
      A second more detailed model considers brain voltages as related to clinical deep
      brain stimulation. RESULTS: For the constant current stimuli characteristic of
      widely available American stimulators, stimulus dose is proportional to current
      cubed multiplied by charge. This relationship corresponds to the 3 dimensions of
      a voltage field in space, where the volume above a certain voltage increases with
      the cube of the voltage radius. As a consequence, any particular charge at 0.9 A
      (ampere) current has a seizure foci dose approximately 50% higher than the same
      charge at 0.8 A. CONCLUSIONS: The modeling offers an explanation for published
      measurements comparing instruments of maximum current 0.8 and 0.9 A. The modeling
      also suggests compensation approaches to be applied to the age-based bilateral
      stimulus dosing method. An electrical dosing strategy based on "half-age" (2.5
      mC/y) is reasonable for 0.9-A stimulation but a "three-quarters age" (3.7 mC/y)
      is more appropriate for 0.8-A stimulation. The present results can allow doses
      and seizure thresholds to be compared between different currents, as when
      substituting one electroconvulsive therapy instrument for another.

PMID- 16633210
TI  - Combined use of electroconvulsive therapy and antipsychotics in schizophrenia:
      the Indian evidence. A review and a meta-analysis.
AB  - BACKGROUND: Combined use of electroconvulsive therapy (ECT) and antipsychotics in
      acute phases of schizophrenia remains controversial and inadequately
      investigated. AIM: This study tried to examine whether the ECT-antipsychotic
      combination was more efficacious than antipsychotic drugs used alone in the acute
      phase treatment of schizophrenia, by way of an open review and an exploratory
      meta-analysis of the Indian studies on the subject. METHOD: Eleven studies (n =
      651) and 4 controlled trials (n = 113) were selected for the open review and the
      meta-analysis, respectively. For the meta-analysis, a standard chi analysis was
      undertaken to check for heterogeneity. Brief Psychiatric Rating Scale scores were
      used to estimate treatment effects. RESULTS: The open review suggested that the
      ECT-antipsychotic combination was more efficacious than antipsychotic drugs used
      alone in the first few weeks of treatment of schizophrenia. The meta-analysis,
      using the Inverse Weighted Variance Model, showed that the ECT-antipsychotic
      combination provides an advantage of approximately 5 Brief Psychiatric Rating
      Scale points over antipsychotic drugs, in the first 4 to 5 weeks of treatment of
      schizophrenia (mean treatment effect, 4.89; 95% confidence intervals, 0.50-9.38).
      CONCLUSIONS: The studies reviewed thus indicated that ECT-antipsychotic
      combinations might be better than antipsychotic drugs used alone in the first few
      weeks of treatment of schizophrenia; the main benefit seemed to be an
      acceleration of treatment response. Although the evidence was not conclusive
      because of several methodological difficulties, it does suggest that further
      research is required to determine the usefulness of the ECT-antipsychotic
      combination in the acute treatment of schizophrenia.

PMID- 16633211
TI  - Acute embolic stroke after electroconvulsive therapy.
AB  - This is the case report of a 44-year-old woman presented with an acute stroke
      immediately after electroconvulsive therapy (ECT). The patient had no significant
      medical history other than chronic depression. She was taking sertraline, and she
      had had multiple previous ECT treatments without any complications. While being
      monitored in the recovery room within 10 minutes after the last ECT session, she
      was found to have sudden onset of left-sided flaccid hemiplegia and numbness
      along with slurred speech. On arrival to our hospital, she was found to have
      flaccid hemiplegia on the left side involving the face, arm, and leg (face and
      arm more than the leg involvement), severe dysarthria, and mild neglect syndrome
      (National Health Institute Stroke Scale of 14). Noncontrast computed tomography
      (CT) of the head showed no signs of early ischemia, and iodine contrast CT
      angiography revealed right middle cerebral artery (MCA) (distal M1 segment) clot.
      Patient received intravenous recombinant tissue plasminogen (rt-PA) at 2.5 hours
      after the onset of symptoms, and then a total of 3.0 mg of intra-arterial (IA) rt
      PA. Angiography at the end of the procedure showed successful recanalization of
      the M1 segment and normal vessel caliber with adequate distal flow. After the
      procedure, the patient made rapid improvements in all of her initial symptoms
      during the first 24 hours. An extensive stroke workup failed to reveal any cause
      of the stroke, including usual stroke and hypercoagulable risk factors. This was
      an acute embolic stroke immediately following an ECT, and without the aggressive
      thrombolytic therapy, the patient's outcome would have been poor because there
      was an M1 segment clot with a major MCA syndrome with relatively high National
      Institute of Health Stroke Scale. The neurological side effect profile of ECT is
      reported to be minimal with most common symptoms being headache, disorientation,
      and memory complaints. There is no clear cause-and-effect relationship in this
      case, and the stroke after ECT is extremely rare. In such rare event of stroke
      while receiving ECT, there is an effective treatment available using both
      intravenous and IA thrombolysis as reported in this case.

PMID- 16633212
TI  - Electroconvulsive therapy-induced symptomatic hypocalcemia in a schizophrenic
      patient: a case report.
AB  - We present a case study of a young schizophrenic 20-year-old female patient,
      admitted for severe psychotic exacerbation unresponsive to several antipsychotic
      regimens. She was treated successfully with a course of bilateral
      electroconvulsive therapy, but developed symptomatic hypocalcemia of short
      duration after the fifth ECT treatment. There is limited information regarding
      the phenomenon of ECT-induced acute hypocalcemia. To the best of our knowledge,
      there are no previous reports of this finding in the literature. A similar
      phenomenon was reported many years ago in patients with primary affective
      illness. The possible mechanisms of this potentially life-threatening reaction
      are not clear and should be evaluated in further studies.

PMID- 16633213
TI  - Electroconvulsive therapy for treatment of refractory depression in a patient
      with cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive inherited disease that is usually
      first diagnosed in early childhood. It is a chronic and progressive disease in
      which mucus builds up and clogs passages in many body organs, but primarily the
      lungs and pancreas. We present a case report of a 42-year-old man with CF who was
      treated with electroconvulsive therapy for treatment-refractory major depressive
      disorder. For patients with CF, the primary issue is anesthetic management in a
      patient with impaired pulmonary function. Our patient received prednisone and
      intravenous antibiotics to optimize pulmonary status. He responded positively to
      the electroconvulsive therapy and was able to tolerate it without significant
      problems.

PMID- 16633214
TI  - Increased thalamostriatal-mesiotemporal glucose uptake with symptom remission in
      schizophrenia--a case report.
AB  - Electroconvulsive therapy (ECT) is an effective modality of treatment, especially
      in medication-resistant psychiatric conditions. We report the case of an
      individual with schizophrenia and prominent negative symptoms who, despite poor
      response to medications, exhibited significant symptom remission with ECT. Post
      ECT fluoro-2-deoxy-D-glucose positron emission tomography scan revealed increased
      uptake in the thalamostriatal-mesiotemporal regions, suggesting a possible
      mechanism of action of ect in alleviation of negative symptoms.

PMID- 16633215
TI  - Monosymptomatic delusional disorder with delusion of poverty.

PMID- 16633218
TI  - Frequency doubling technology perimetry with the Humphrey Matrix 30-2 test.
AB  - PURPOSE: To assess the Humphrey Matrix 30-2 test in detecting functional
      glaucomatous damage. PATIENTS AND METHODS: One eye in each of 60 healthy
      individuals, 108 patients with ocular hypertension (OHT), and 150 patients with
      preperimetric (48) or perimetric (102) high-tension primary open-angle glaucoma
      (POAG) were considered. Visual fields were assessed by the standard automated
      perimetry (SAP) Humphrey Field Analyzer 30-2, frequency doubling technology (FDT)
      N-30, and Humphrey Matrix 30-2 tests. Significantly abnormal points in the
      pattern deviation probability plot, testing time, sensitivity, specificity, and
      area under the receiver operating characteristic curve of the FDT tests were
      evaluated. RESULTS: FDT revealed a significantly greater percentage of depressed
      points than did SAP in OHT and preperimetric POAG eyes. The FDT-N-30 test showed
      a significantly greater percentage of areas with P < 5% in the OHT, preperimetric
      POAG, and early POAG groups. The Matrix-30-2 test provided an area under the
      receiver operating characteristic curve slightly lower than the FDT-N-30 test in
      the preperimetric POAG group, and significantly greater in the perimetric POAG
      group. CONCLUSIONS: FDT perimetry appeared more sensitive than SAP in detecting
      early glaucomatous VF loss. The FDT-N-30 test showed a slightly higher ability to
      detect early glaucomatous damage in patients at risk for the development of
      glaucoma, whereas the Matrix-30-2 test provided a more detailed characterization
      of the glaucomatous VF loss pattern, although it required 30% more time.

PMID- 16633219
TI  - Determinants of bleb morphology in minimally invasive, clear-cornea
      micropenetrating glaucoma surgery with mitomycin C.
AB  - PURPOSE: Antimetabolites, especially mitomycin C (MMC), increase the incidence of
      late bleb-related endophthalmitis in trabeculectomy. This is related to a higher
      incidence of avascular, thin, cystic, translucent blebs, which may be caused by a
      toxic effect on conjunctival tissue. An MMC dose-response study was carried out
      focusing on bleb morphology and function. PATIENTS AND METHODS: In a
      retrospective, comparative case series study, 2 successive groups of patients
      with complicated glaucoma were compared 2 years after a special, minimally
      invasive, filtering procedure (intrastromal holmium laser keratostomy).
      Preoperative local subconjunctival injections of a fixed MMC dose (4 microg) were
      used in group A, and lower MMC doses, calculated individually (1 or 2 microg),
      were used in group B. Bleb vascularity and morphology were evaluated by masked
      grading of photomicrographs. Bleb function was evaluated by intraocular pressure
      (IOP). RESULTS: Total bleb avascularity occurred in 63% of the blebs in group A
      and 0% in group B (P < 0.01). In eyes with IOP < or = 20 mmHg without medical
      treatment, the mean IOP was significantly lower in group 1 (8 vs 15 mm Hg, P <
      0.002). A translucent cystic bleb without conjunctival stroma was observed in
      only 1 eye in group A. An optimal spongy stromal bleb was observed in all other
      eyes (96%) despite the different MMC doses. The numbers of complications in the 2
      groups were nearly equal. CONCLUSIONS: Bleb avascularity after 4 microg MMC could
      be avoided by the use of 1 or 2 microg MMC on the basis of preoperative
      prognosticators for failure, but at the expense of some of the IOP-lowering
      effect. This indicates that the therapeutic index (clinical safety margin) of MMC
      seems to be narrow. An MMC dose-response relation was not observed for the thin,
      cystic, and translucent bleb. The low incidence of this bleb (4%) indicates that
      the operative technique, apart from the vascularity, may be the most essential
      determinant of bleb morphology.

PMID- 16633220
TI  - Correlation between intraocular pressure, central corneal thickness, stage of
      glaucoma, and demographic patient data: prospective analysis of biophysical
      parameters in tertiary glaucoma practice populations.
AB  - PURPOSE: To determine the correlation of central corneal thickness (CCT) to
      Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT, PASCAL),
      and to glaucoma stage as assessed by cup-to-disc ratio (CDR). DESIGN:
      Prospective, cross-sectional tricenter observation study. PATIENTS AND METHODS:
      From three glaucoma specialty practices a sample of 406 independent eyes was
      included. After ultrasound pachymetry, intraocular pressure was measured using
      PASCAL and Goldmann applanation tonometry and cup-to-disc ration was reassessed.
      Demographic data were included in the multivariate analysis. RESULTS: Mean
      corneal thickness was 540 microm. African Americans and normal-tension glaucoma
      patients showed the lowest values (518 microm and 522 microm, respectively).
      These values were significantly thinner than the central corneal thickness of
      Caucasians (549 microm) and ocular hypertensives (564 microm). Intraocular
      pressure assessed by Goldmann applanation tonometry shows a significant
      correlation with central corneal thickness (r = 0.068, P < 0.001), whereas PASCAL
      is not significantly associated with central corneal thickness (r < 0.001, P =
      0.997). Increased IOP is significantly correlated with large ocular pulse
      amplitudes (r = 0.13, P < 0.001), which is predominantly seen in ocular
      hypertensives. A significant negative correlation was detected between cup-to
      disc ratio and central corneal thickness (r = 0.102, P < 0.001). CONCLUSION:
      Glaucoma patients with thin central corneal thickness are more likely to be found
      at an advanced stage of the disease and among those with normal-tension glaucoma
      and black African ancestry. Underestimation of intraocular pressure by Goldmann
      applanation tonometry could be one causative factor.

PMID- 16633221
TI  - Prospective evaluation of preoperative factors associated with successful
      mitomycin C needling of failed filtration blebs.
AB  - PURPOSE: To study the long-term effectiveness and factors involved in successful
      needling of failed filtration blebs with mitomycin C (MMC). MATERIALS AND
      METHODS: We conducted a prospective, nonrandomized comparative trial that
      included 34 consecutive patients (34 eyes) who underwent mitomycin C needling of
      a failed filtering bleb after trabeculectomy followed by a 0.01 mL injection of
      mitomycin C (0.2 mg/ml). The success of the needling revision was defined as
      absolute if the intraocular pressure (IOP) was < 21 mm Hg without antiglaucoma
      medications and qualified if the IOP was < 21 mm Hg with antiglaucoma
      medications. Preoperative and perioperative factors were evaluated for an
      association with postoperative success using Kaplan-Meier survival analysis.
      RESULTS: The mean follow-up was 14.2 +/- 9.8 months. The mean preoperative IOP
      was 25.5 +/- 4.4 mm Hg, which decreased to 11.1, 13.4, 15.8, 16.7, 14.9, 14.1,
      13.9, and 13 on postoperative day 1, postoperative week 1, and after 1, 3, 6, 9,
      12, and 24 months, respectively (P = 0.001 for each comparison). At the final
      visit, success was absolute in 15 eyes (44.1%) and qualified in 14 eyes (41.2%).
      The success rates were 90% and 75% at 1 and 2 years, respectively. The success of
      the needling procedure was highly correlated with glaucoma filtration surgery
      performed less than 4 months previously (Kaplan-Meier analysis, log-rank test P =
      0.006). CONCLUSIONS: Mitomycin C needling revision appears to have a high long
      term success rate. Surgery performed less than 4 months previously contributes to
      the success of the initial mitomycin C needling procedure.

PMID- 16633222
TI  - Effects of small-incision phacoemulsification and intraocular lens implantation
      on anterior chamber depth and intraocular pressure.
AB  - PURPOSE: To examine prospectively the effects of small-incision
      phacoemulsification and intraocular lens implantation (PEA+IOL) on anterior
      chamber depth (ACD) and intraocular pressure (IOP) using a newly developed
      scanning peripheral ACD analyzer (SPAC). MATERIALS AND METHODS: Twenty-eight eyes
      of 21 patients who underwent PEA+IOL without any complications were examined and
      divided into 7 eyes each of grades 1 to 4 according to the Van Herick technique.
      The SPAC measured ACD consecutively from the vicinity of the pupil center to the
      periphery at 0.4-mm intervals. Changes in ACD and IOP as a result of PEA+IOL were
      investigated, and the factors contributing to the changes in ACD and IOP were
      examined. RESULTS: PEA+IOL increased ACD significantly at all groups. The average
      changing rates were 3.19 +/- 0.67 times (Van Herick grade 1), 2.00 +/- 0.80 times
      (Van Herick grade 2), 1.92 +/- 0.32 times (Van Herick grade 3), and 1.36 +/- 0.65
      times (Van Herick grade 4), respectively. The closer to the pupil center the
      measurement point was, the larger was the increase in ACD. However, the rates of
      increase in ACD were similar among the measurement points. The increases in ACD
      were significantly large in patients having a shallow preoperative ACD and a
      small optic axis length. The IOP reduction became significantly large in eyes
      with a shallow preoperative ACD. CONCLUSIONS: The SPAC enabled quantitative
      measurement of changes in ACD from the vicinity of the pupil center to the
      periphery as a result of PEA+IOL. Changes in ACD resulting from PEA+IOL were
      thought to exert a greater effect on aqueous humor outflow facility as the
      postoperative ACD became shallower.

PMID- 16633223
TI  - Comparison of objective diagnostic tests in glaucoma: Heidelberg retinal
      tomography and multifocal visual evoked potentials.
AB  - PURPOSE: To compare sensitivity and specificity of functional and structural
      changes in glaucoma using two objective tests: the multifocal visual evoked
      potential (m-VEP) and Heidelberg retinal tomography II (HRT). PATIENTS AND
      METHODS: 41 glaucoma patients and 25 normal individuals participated in the
      study. One eye per individual was included in the study. Individuals were
      evaluated with Humphrey visual field (HVF) perimetry, m-VEP, and HRT. Moorfield
      regression analysis findings of HRT were compared with presence of scotoma on m
      VEP. Linear regression analysis of quantitative variables, such as HVF mean
      deviation (MD), m-VEP discriminant score (Accumap Severity Index) and, global HRT
      parameters was also performed. RESULTS: m-VEP sensitivity and specificity were
      93% and 96% respectively. HRT sensitivity and specificity were 79% and 92%
      respectively. The area under the receiver operating characteristic curve (ROC)
      for m-VEP was 0.96 and for HRT varied from 0.79 to 0.86 depending on the
      parameters used. Linear correlation between MD and Accumap Severity Index score
      was -77%, while that between HRT global parameters, Accumap Severity Index and MD
      were at best around 50%. Topographic comparison of the presence of scotoma on HVF
      and m-VEP in different areas of the visual field showed good agreement.
      Comparison of optic nerve head structural abnormality with corresponding areas of
      field defects on HVF and m-VEP showed poor to moderate agreement. CONCLUSION: The
      objective test of optic nerve function (m-VEP) and structure (HRT) can detect
      glaucomatous damage, with limited correlation. The 2 functional tests, HVF and m
      VEP correlate better with each other than with HRT. It remains important to look
      for both functional and structural changes in order to detect all glaucoma cases.

PMID- 16633224
TI  - Ultrastructure of the trabecular meshwork in secondary glaucoma eyes after
      intravitreal triamcinolone acetonide.
AB  - PURPOSE: To study the histology of the trabecular meshwork of eyes with glaucoma
      by intravitreal injection of triamcinolone acetonide (TA). DESIGN: Two cases
      report. PARTICIPANTS/METHODS: A 68-year-old Japanese man with branch retinal vein
      occlusion and a 48-year-old Japanese woman with uveitis were treated by cataract
      surgery, intraocular lens implantation, and TA-assisted pars plana vitrectomy. At
      the end of surgery, TA suspension (4 mg) was intravitreously injected. During the
      follow-up period, the intraocular pressure (IOP) of the patients increased over
      30 mm Hg even with full medication. Trabeculectomy was performed at 4 months
      after TA injection in case 1 and at 6 months in case 2, and intraocular pressure
      returned to the normal range in both cases. Light and electron microscopic
      studies of the resected trabecular tissue were carried out. RESULTS: The
      histology showed minimal deposition of extracellular matrix in the trabecular
      meshwork in case 1. Case 2 showed the beginnings of deposition of extracellular
      matrix including fingerprintlike material in the trabecular meshwork with
      decreased intertrabecular spaces. CONCLUSIONS: The ultrastructural changes in the
      trabecular meshwork of eyes with glaucoma after treatment with intravitreal TA
      might resemble those with glaucoma after topical corticosteroid treatment.

PMID- 16633225
TI  - Relationship between central corneal thickness and localized retinal nerve fiber
      layer defect in normal-tension glaucoma.
AB  - PURPOSE: To determine whether central corneal thickness (CCT) is related to the
      extent of localized retinal nerve fiber layer (RNFL) defect at the initial
      examination of normal-tension glaucoma (NTG) patients. PATIENTS AND METHODS:
      Seventy-five eyes of 75 NTG patients showing localized RNFL defects on RNFL
      photographs and corresponding visual field defects at the initial visit to a
      glaucoma specialist were selected for this study. All participants completed
      refraction, Goldmann applanation tonometry, CCT measurement, stereoscopic disc
      photography, RNFL photography, and automated perimetry. Each patient's age,
      spherical equivalent, intraocular pressure, CCT, approximation of the RNFL defect
      to the fovea (angle alpha), circumferential width of the RNFL defects (angle
      beta), horizontal and vertical cup-to-disc ratios, and mean deviation of visual
      field were analyzed. RESULTS: In univariate and multivariate analyses, lower CCT
      was significantly associated with increased horizontal and vertical cup-to-disc
      ratios, decreased angle alpha, and increased angle beta. For a decrease of 10
      microm of CCT, horizontal and vertical cup-to-disc ratios increased by 0.020,
      angle alpha decreased by 1.58 degrees, and angle beta increased by 1.71 degrees,
      respectively. CONCLUSION: CCT is a significant factor in predicting the extent of
      localized RNFL defect at the initial examination of NTG patients.

PMID- 16633226
TI  - Selective laser trabeculoplasty as initial and adjunctive treatment for open
      angle glaucoma.
AB  - PURPOSE: To investigate the efficacy and safety of selective laser
      trabeculoplasty as an initial treatment for newly diagnosed open-angle glaucoma,
      and its role as adjunctive therapy. PATIENTS AND METHODS: A prospective
      multicenter nonrandomized clinical trial was performed. Patients with newly
      diagnosed open-angle glaucoma or ocular hypertension were assigned to the primary
      (selective laser trabeculoplasty) treatment group or the control (latanoprost)
      group according to patient choice. Both groups were followed up at 1, 3, 6, and
      12 months. A secondary treatment group was also included to study the efficacy of
      selective laser trabeculoplasty for patients intolerant of medical therapy or in
      whom such therapy was unsuccessful, with or without a history of previous argon
      laser trabeculoplasty. RESULTS: One hundred eyes (61 patients) were enrolled, 74
      in the primary treatment group and 26 in the control group. The average absolute
      and percent reductions in intraocular pressure for the primary treatment group
      were 8.3 mm Hg or 31.0%, compared with 7.7 mm Hg or 30.6% for the control group
      (P = 0.208 and P = 0.879). The responder rates (20% pressure reduction) were 83%
      and 84% for the primary and control groups, respectively. There were no
      differences in intraocular pressure lowering with selective laser trabeculoplasty
      on the basis of angle pigmentation. A modest contralateral effect was observed in
      the untreated fellow eyes of patients undergoing selective laser trabeculoplasty.
      CONCLUSIONS: Selective laser trabeculoplasty was found to be equally efficacious
      as latanoprost in reducing intraocular pressure in newly diagnosed open-angle
      glaucoma and ocular hypertension over 12 months, independent of angle
      pigmentation. Nonsteroidal antiinflammatory therapy had similar efficacy to
      steroids after laser therapy. These findings support the consideration of
      selective laser trabeculoplasty as a first-line treatment for newly diagnosed
      open-angle glaucoma or ocular hypertension.

PMID- 16633227
TI  - Repeatability of normal multifocal VEP: implications for detecting progression.
AB  - PURPOSE: To assess the repeatability of the multifocal visual evoked potential
      (mfVEP) and to compare it with the repeatability of standard automated perimetry
      (SAP) in the same group of 50 normal controls retested after 1 year. Our second
      aim was to assess the repeatability of false alarm rates determined previously
      for the mfVEP using various cluster criteria. METHODS: Fifty individuals with
      normal vision participated in this study (33 females and 17 males). The age range
      was 26.7 to 77.9 years and the group average age (+/- SD) was 51.4 (+/- 12.1)
      years. Pattern-reversal mfVEPs were obtained using a dartboard stimulus pattern
      in VERIS and two 8-minute runs per eye were averaged. The average number of days
      between the first and second mfVEP tests was 378 (+/- 58). SAP visual fields were
      obtained within 17.4 (+/- 20.3) days of the mfVEP using the SITA-standard
      threshold algorithm. Repeatability of mfVEPs and SAP total deviation values were
      evaluated by calculating point-wise limits of agreement (LOA). Specificity (1
      false alarm rate) was evaluated for a range of cluster criteria, whereby the
      number and probability level of the points defining a cluster were varied.
      RESULTS: Point-wise LOA for the mfVEP signal-to-noise ratio (SNR) ranged from 2.0
      to 4.3 dB, with an average of 2.9 dB across all 60 locations. For SAP, LOA ranged
      from 2.4 to 8.9 dB, with an average of 4.0 dB (excluding the points immediately
      above and below the blind spot). Clusters of abnormal points were not likely to
      repeat on either mfVEP or SAP. When an mfVEP abnormality was defined as the
      repeat presence (confirmation) of a 3-point (P < 0.05) cluster anywhere within a
      single hemifield, only 1 (of 200) monocular hemifield was deemed abnormal.
      Although the LOA of the mfVEP were similar throughout the field, the limited
      dynamic range of SNR at superior field locations will limit the ability to follow
      progression in "depth" at those locations. CONCLUSIONS: Repeatability of the
      mfVEP was slightly better than SAP visual fields in this group of controls with a
      1-year retest interval. This suggests that progression in early stages should be
      more easily detectable by mfVEP. However, in certain field locations (eg,
      superior periphery), the relatively more narrow dynamic range of the SNR of the
      mfVEP may limit detection of progression to just 1 event. Confirmation of a 3
      point cluster abnormality is highly suggestive of a true defect on the mfVEP.

PMID- 16633228
TI  - Histologic findings in pigment dispersion syndrome and pigmentary glaucoma.
AB  - PURPOSE: To investigate the morphologic changes in the trabecular meshwork in a
      case series of eyes with pigment dispersion syndrome and pigmentary glaucoma, and
      surgical trabeculectomy specimens from eyes with pigmentary glaucoma. MATERIALS
      AND METHODS: Trabecular meshworks from 6 whole eyes from 3 donors and 7
      trabeculectomy specimens were studied by light and electron microscopy. Axonal
      counts from the whole eyes were correlated with qualitative and quantitative data
      of meshwork changes. RESULTS: Changes in the meshwork varied around the
      circumference of the eyes, but in all 6 eyes in most regions of the circumference
      there were numerous pigment granules within trabecular cells; pigment was not
      found within intertrabecular or cribriform spaces. In some regions of the
      circumference there was trabecular cell loss, loss of intertrabecular spaces,
      fusion of lamellae, and an increase in extracellular material under the inner
      wall of the canal. Separation of the normal tendinous connection to the canal
      wall cells was noted in some regions of all eyes. This change could be associated
      with regions of pathologic separation of the inner wall from the cribriform
      region, associated with partial obliteration of the lumen of the canal with cells
      and cell processes. In eyes with pronounced axon loss, meshworks showed most
      pronounced loss of trabecular cells and increased extracellular material.
      Trabeculectomy specimens had similar changes and, in addition, showed damaged
      trabecular cells and collapse of intertrabecular spaces without fusion of
      lamellae, consistent with artifacts from manipulation during surgery.
      CONCLUSIONS: Loss of trabecular cells, fusion of trabecular lamellae with
      collapse of intertrabecular spaces, increase in extracellular material, and
      obliteration of the canal were found in various amounts around the circumference
      of eyes with pigment dispersion syndrome and elevated intraocular pressure, and
      pigmentary glaucoma. These probably all contribute to the development of
      increased intraocular pressure. Meshworks from trabeculectomy specimens showed
      these findings and also showed artifactual damage of cells and loss of
      intertrabecular spaces. This suggests that handling during surgery may cause
      single trabeculectomy specimens to give only an incomplete picture of the
      pathophysiology of pigmentary glaucoma.

PMID- 16633229
TI  - Test-retest variability in structural and functional parameters of glaucoma
      damage in the glaucoma imaging longitudinal study.
AB  - PURPOSE: To determine the test-retest variability in perimetric, optic disc, and
      macular thickness parameters in a cohort of treated patients with established
      glaucoma. PATIENTS AND METHODS: In this cohort study, the authors analyzed the
      imaging studies and visual field tests at the baseline and 6-month visits of 162
      eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They
      assessed the difference, expressed as the standard error of measurement, of
      Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast,
      Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA)
      parameters between the two visits and assumed that this difference was due to
      measurement variability, not pathologic change. A statistically significant
      change was defined as twice the standard error of measurement. RESULTS: In this
      cohort of treated glaucoma patients, it was found that statistically significant
      changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation
      (PSD), 0.12 for cup shape measure, 0.26 mm for rim area, and 32.8 microm and 31.8
      microm for superior and inferior macular thickness, respectively. On the basis of
      these values, it was estimated that the number of potential progression events
      detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim
      area, superior macular thickness, and inferior macular thickness was 7.5, 6.0,
      2.3, 5.7, 3.1, and 3.4, respectively. CONCLUSIONS: The variability of the
      measurements of MD, PSD, and rim area, relative to the range of possible values,
      is less than the variability of cup shape measure or macular thickness
      measurements. Therefore, the former measurements may be more useful global
      measurements for assessing progressive glaucoma damage.

PMID- 16633230
TI  - Laser bleb reduction for bleb dissection with krypton green laser: technique and
      outcomes.
AB  - PURPOSE: Lasers have been used to treat dysfunctional blebs, but the laser
      remodeling of blebs that dissect into the palpebral fissure has not been
      reported. We describe the unique use of krypton green laser to treat dissected
      blebs and discuss treatment outcomes. PATIENTS AND METHODS: Retrospective review
      of consecutive patients undergoing laser bleb reductions (LBRs) over a 6-year
      period. Failure was defined as persistent dissection and/or symptoms or loss of
      intraocular pressure (IOP) control despite medications. RESULTS: Sixteen patients
      underwent a total of 23 LBRs and were followed-up for a mean of 12.4 months
      (median = 9.5 mo). Ten patients (63%) were treated successfully, and 6 patients
      (37%) failed treatment. Persistent dissection and/or symptoms were the most
      common reasons for failure (5/6), whereas 1 patient lost IOP control. Three (30%)
      of those treated successfully required the reintroduction of ocular hypotensive
      medications for pressure control. The mean IOP increased from 9.1 +/- 5.2 mm Hg
      before treatment to 11.7 +/- 8.1 mm Hg after treatment (P = 0.02). Common
      complications included intraoperative discomfort (26%), conjunctival injection
      (22%), postoperative discomfort (13%), and dissection into the untreated side
      (9%). In the failure group, more laser spots (P = 0.05) and higher power levels
      (P = 0.00001) were used. CONCLUSIONS: Krypton LBR may be a useful initial
      treatment modality for symptomatic bleb dissection. Success rates may be modest,
      but most adverse effects are mild and/or transient; however, significant loss of
      IOP control can occasionally occur.

PMID- 16633231
TI  - Incidence of disc hemorrhages in open-angle glaucoma before and after
      trabeculectomy.
AB  - PURPOSE: To investigate the effects of reduction of intraocular pressure (IOP) by
      surgical intervention on the frequency of disc hemorrhages in eyes with primary
      open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). DESIGN:
      Retrospective study. METHODS: We studied 99 eyes of 99 patients with POAG and 50
      eyes of 50 patients with NTG, who underwent trabeculectomy with adjunctive
      mitomycin C (MMC) and were followed regularly at 1 to 3-month intervals at the
      Glaucoma Service of Gifu University Hospital. We applied Kaplan-Meier life-table
      analysis for the detection of disc hemorrhages before and after trabeculectomy.
      RESULTS: Trabeculectomy significantly reduced IOP (in POAG: 19.6 +/- 4.4 down to
      11.1 +/- 4.2 mm Hg; in NTG: 15.3 +/- 1.5 down to 11.3 +/- 4.5 mm Hg; mean +/-
      SD). Life-table analysis revealed that the final cumulative probability of
      detecting a disc hemorrhage after surgery in POAG was 5.5 +/- 2.2% (calculated
      probability +/- SE) and was significantly lower than that (33.4 +/- 7.8%) before
      surgery (P < 0.0001, log-rank test). Likewise, the final probability after
      surgery in NTG was 23.1 +/- 6.3% and was significantly lower than that (42.1 +/-
      8.8%) before surgery (P = 0.0063, log-rank test). CONCLUSIONS: IOP reduction via
      surgical intervention significantly decreases the frequency of disc hemorrhages
      in open-angle glaucoma patients.

PMID- 16633232
TI  - Relationship between ciliary blood flow and aqueous production: does it play a
      role in glaucoma therapy?
AB  - This review will summarize the authors' recent studies of the relationship
      between ciliary blood flow and aqueous production, and discuss the relevance of
      that relationship to the mechanisms of action of glaucoma drugs that lower
      intraocular pressure by inhibiting aqueous production. The ciliary processes are
      not easily accessible, and so the data presented necessarily come from animals
      and from instrumentation operated at its engineering limits. Verification of the
      findings in humans, and perhaps refinement of the interpretations, must await
      future advances in technology. Nonetheless, the results to date are intriguing,
      and may help explain some paradoxes in glaucoma pharmacology.

PMID- 16633234
TI  - Macular symmetry testing for glaucoma detection.

PMID- 16633235
TI  - Colposcopy for gland (crypt) openings.
AB  - Systematic observation of the gland(crypt) openings of the uterine cervix is
      essential to colposcopy.

PMID- 16633236
TI  - Assessment of 2 cervical screening methods in Mongolia: cervical cytology and
      visual inspection with acetic acid.
AB  - OBJECTIVE: The aim of the study was to evaluate the test parameters of visual
      inspection with acetic acid (VIA) and cervical cytology in 3 Mongolian aimags.
      METHODS: From February 18, 2002, to December 12, 2004, sexually active women, 30
      years or older who had never been screened, underwent cervical cytology and VIA
      in the aimags' central hospital. Women with abnormal test results and 5% of women
      with normal results were recommended to have colposcopy with or without biopsy.
      RESULTS: Two thousand nine women underwent both tests. Visual inspection with
      acetic acid was abnormal in 254 (12.6%); Pap smear showed atypical squamous cells
      of undetermined significance or worse in 3%. Using cervical intraepithelial
      neoplasia 2 or higher disease on biopsy as the end point, the test parameters for
      VIA are sensitivity of 82.9% (95% CI = 81.3%-84.5%), specificity of 88.6% (95% CI
      = 87.2%-90.0%), positive predictive value of 12.2% (95% CI = 10.8%-13.6%), and
      negative predicative value of 99.7% (95% CI = 99.5%-99.9%). The test parameters
      for Pap smear are sensitivity of 88.6% (95% CI = 87.2%-90.0%), specificity of
      98.5% (95% CI = 98.0%-99.0%), positive predictive value of 51.7% (95% CI = 49.5%
      53.9%), and negative predicative value of 99.8% (95% CI = 99.6%-100%).
      CONCLUSION: Visual inspection with acetic acid has an acceptable test parameter
      for population-based cervical screening in Mongolia.

PMID- 16633237
TI  - Admission for treatment--does the degree of training of colposcopist make a
      difference?
AB  - AIM: The aim of the study was to assess whether the degree of training of
      colposcopist making the decision has an influence on the number of inpatient
      treatments. METHOD: A retrospective audit was performed of patients who underwent
      surgical excision of cervical transformation zone for cervical intraepithelial
      neoplasia over a period of 23 months from February 2003 to December 2004. Case
      notes were reviewed for patients undergoing inpatient treatment, and database
      interrogation was done for patients who had an outpatient treatment. Data were
      collected with regard to indication for referral, person making the decision, and
      the indications for inpatient treatment. RESULTS: Three hundred thirty-one cases
      were reviewed. Inpatient treatment was performed in 61 (18.42%) and outpatient in
      270 (81.57%). Inpatient procedures were chosen in 13% of cases by a consultant,
      27% by a trained nurse, 18% by a trainee, and 14% by an associate specialist. The
      main indications where there was a difference in decision making was anxiety,
      access, and size of lesion. CONCLUSION: We achieved the standard of performing
      loop excision as an inpatient procedure in less than 20% of cases. A nurse and a
      trainee, compared with a consultant, referred a greater proportion of patients
      for an inpatient procedure. Improved training and confidence building may achieve
      a further reduction in the inpatient referral.

PMID- 16633238
TI  - Hormone replacement therapy in endometrial cancer survivors: new perspectives
      after the heart and estrogen progestin replacement study and the women's health
      initiative.
AB  - OBJECTIVE: Dramatic shifts in prescription practices during the last 30 years
      have left physicians confused and uncertain about the use of hormone replacement
      therapy (HRT) in endometrial cancer survivors. MATERIALS AND METHODS: This
      article reviews the published literature concerning both the safety of
      prescribing HRT to endometrial cancer survivors and the therapy s potential risks
      and benefits. RESULTS: Prescribing HRT to endometrial cancer survivors does not
      seem to be contraindicated and may even confer modest protection, depending on
      the doses and the specific drugs used. The potential benefits of HRT are more
      conflicting. Although the medical community agrees on the positive effects for
      bone density and relief of vasomotor symptoms, the results of our review offer no
      clear consensus in regard to HRT's effects on coronary heart disease, health
      related quality of life, cognitive functioning, and cancer incidence.
      CONCLUSIONS: Until the medical community can concur on the proper prescription
      practices in endometrial cancer survivors, an individualized patient-based
      approach must be taken.

PMID- 16633239
TI  - Hormonal contraception and false-positive cervical cytology: is there an
      association?
AB  - OBJECTIVE: The aim of the study was to determine if use of hormonal contraception
      influences the false-positive rate of cervical cytology when compared with loop
      electrosurgical excision procedure or cervical biopsy specimens. MATERIALS AND
      METHODS: We performed a case-control analysis of 328 women referred for
      colposcopy after an abnormal Pap test. Patients were divided into cases (true
      positive cytology results) and controls (false-positive cytology results).
      Univariate analysis was performed using the chi and Student t test to identify
      factors associated with false-positive cytology. Multiple logistic regression
      analysis was used to estimate odds ratios for the independent association of
      these factors. RESULTS: The false-positive rate for the entire cohort was 44.8%.
      Cases were more likely to be pregnant and postmenopausal (odds ratio [OR] = 4.98,
      95% CI = 2.16-11.47; OR = 5.48, 95% CI = 1.23-24.36, respectively). Use of
      hormonal contraception was not significantly different between groups (OR = 0.56,
      95% CI = 0.29-1.09 for combination oral contraceptive pills; OR = 0.89, 95% CI =
      0.35-2.25 for progestin-containing contraception). Low-grade squamous
      intraepithelial lesion results were more likely to be false positives (51%) than
      high-grade squamous intraepithelial lesion (27%) (p <.001). CONCLUSIONS: There
      remains a substantial lack of correlation between cervical cytology and
      histology. Use of hormonal contraception was not shown to increase a patient's
      likelihood of having a false-positive Pap test.

PMID- 16633240
TI  - Cavernous hemangioma of the cervix: a rare cause of vaginal bleeding.
AB  - Cavernous hemangiomas of the cervix are extremely rare, benign lesions. To date,
      fewer than 50 cases have been reported. Here reported is a case of cavernous
      hemangioma of the cervix in a 53-year-old patient with the complaint of
      postcoital spotting. Most of these lesions are asymptomatic incidental findings,
      but sometimes, they may cause abnormal vaginal bleeding in the form of
      menometrorrhagia and postcoital spotting. They should be included in the
      differential diagnosis of patients with vaginal bleeding.

PMID- 16633241
TI  - On maintaining the balance.
AB  - Recent studies have shown an association of loop electrocautery excision
      procedure (LEEP) with subsequent obstetric complications, including preterm
      birth. These data necessitate a reevaluation of how LEEP is used, particularly in
      cases where the presence of a high-grade lesion has not been established. In the
      2001 consensus guidelines, nonadolescent women with high-grade cytology and
      subsequent negative colposcopy and endocervical curettage are recommended to
      undergo LEEP for further evaluation. Given the new information on potential
      obstetric complications and the rising age of childbearing, it is debatable
      whether the benefits of LEEP in this situation truly outweigh the risks for all
      women, regardless of age, who have not completed childbearing. We urge the
      committee charged with revising the guidelines to carefully consider this issue.

PMID- 16633242
TI  - Endometrial cells in cervical cytology: review of cytological features and
      clinical assessment.
AB  - The 2001 Bethesda System for Reporting Cervical Cytology recommends reporting
      benign exfoliated endometrial cells in women age 40 and older, and a review of
      the literature supports this recommendation. Stromal cells and histiocytes do not
      need to be reported. The effect of hormonal therapy on endometrial shedding is
      reviewed. Clinical information should be provided to the laboratory so that
      appropriate educational notes can be appended to the cytology report. Benign
      endometrial cells in premenopausal women in the first half of the cycle are not
      associated with significant pathology and such women do not need additional
      evaluation. Significant pathology is also unlikely in the second half of the
      cycle and evaluation may not be required unless clinically indicated. Initial
      evaluation of other women with benign endometrial cells may include either
      endometrial sampling or transvaginal ultrasound. Atypical endometrial cells are
      associated with a higher rate of significant pathology and should lead to
      additional evaluation. Additional prospective studies on the management of
      patients with endometrial cells on Pap tests are needed.

PMID- 16633243
TI  - Home Study Course: Spring 2006.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or hercolposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or to present
      colposcopic cases that demonstrate new and important knowledge in the area of
      colposcopyor pathology. Participants may benefit from reading and studying the
      material or from testing their knowledge by answering the questions. ACCME
      ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP)
      is accredited by the Accreditation Council for Continuing Medical Education
      (ACCME) to provide continuing medical education for physicians. The ASCCP
      designates this continuing medicaleducation activity for 1 hour category 1 credit
      of the ASCCP's Program for Continuing Professional Development and the
      Physician's Recognition Award of the American Medical Association. Credit is
      available for those who choose to apply. The Home Study Course is planned and
      produced in accordance with the ACCME's Essential Areas and Elements. DISCLOSURE:
      Faculty must disclose any significant financial interest or relationship with
      proprietary entities that may have a directrelationship to the subject matter.
      For this course, the author had no such relationship to report.

PMID- 16633245
TI  - Colposcopic proficiency.

PMID- 16633247
TI  - Critical care performance measurement: the time has come for all.

PMID- 16633248
TI  - Lessons learned: the conditional importance of high positive end-expiratory
      pressure in acute respiratory distress syndrome.

PMID- 16633249
TI  - Immunoglobulin treatment in sepsis--is the answer "no"?

PMID- 16633250
TI  - The long and short of sedation practices: daily interruption or bolus dosing?

PMID- 16633251
TI  - Electrocardiographic diagnosis of coronary syndromes in the critical care unit.

PMID- 16633252
TI  - Preventing postextubation respiratory failure.

PMID- 16633253
TI  - Catecholamines, parasympathetic stimuli, or cortisol for overwhelming sepsis?

PMID- 16633254
TI  - Extracorporeal support and patient outcome: credible causality remains elusive.

PMID- 16633255
TI  - What accounts for the difference between observed and predicted?

PMID- 16633256
TI  - Customizing lung-protective mechanical ventilation strategies.

PMID- 16633257
TI  - Esophageal and transpulmonary pressure help optimize mechanical ventilation in
      patients with acute lung injury.

PMID- 16633258
TI  - Comfortably numb in the intensive care unit.

PMID- 16633259
TI  - Predicting response to fluid administration: something old, something new?

PMID- 16633260
TI  - Diagnostic and scientific dilemma: the ischemic bowel.

PMID- 16633261
TI  - Hypoxic pulmonary vasoconstriction after combined burn and inhalation injury.

PMID- 16633262
TI  - Tuning up the compression and applying the choke for better horsepower in
      resuscitation.

PMID- 16633263
TI  - The incomplete puzzle of vasoactive medication in (abdominal) sepsis.

PMID- 16633264
TI  - Can the effects of vasoactivity of molecular hemoglobin-based plasma expanders be
      ignored?

PMID- 16633265
TI  - Controlling the cytokine storm by insulin: glycogen synthase kinase-3 as a target
      in systemic inflammation.

PMID- 16633266
TI  - Pressure pulse waveform analysis in critical care.

PMID- 16633267
TI  - Ischemia-reperfusion: putting the pieces of the puzzle together.

PMID- 16633268
TI  - Modulating the oral colonization with povidone-iodine antiseptic: a new approach
      for an old controversy.

PMID- 16633269
TI  - Improved prediction of awakening or nonawakening in severe anoxic coma using tree
      based classification.

PMID- 16633270
TI  - Acknowledging our mistakes.

PMID- 16633272
TI  - There is a role for nonbronchoscopic lavage for investigating alveolar
      inflammation in acute respiratory distress syndrome.

PMID- 16633274
TI  - High-frequency oscillation and prone position.

PMID- 16633275
TI  - Multidisciplinary critical care: right care, right now.

PMID- 16633276
TI  - Barriers in the United States to obtaining certification in critical care
      medicine.

PMID- 16633277
TI  - The case for sodium-hydrogen exchanger isoform-1 inhibition during cardiac
      resuscitation remains strong.

PMID- 16633279
TI  - Need for intracranial pressure monitoring following severe traumatic brain
      injury.

PMID- 16633283
TI  - The effects of the addition of glutamine to enteral feeds require careful
      evaluation.

PMID- 16633284
TI  - About global volume-related hemodynamic variables and outcome.

PMID- 16633286
TI  - [Programmes against depression].
AB  - BACKGROUND: Depressive disorders represent a major public health concern,
      regarding their high frequency and their important cost. Depression impair the
      quality of life more than any other disease, sometimes leading to suicidal ideas
      or behavior. Indeed, 50% of patients with severe major depression commit suicide.
      Numerous studies showed that depressive disorders are frequently not recognised,
      and regularly untreated. In France, where at least 3 millions of inhabitants are
      concerned, 38% of depressed patients are not using any health system. When they
      are asking for care, the majority of depressed patients visit their general
      practitioner (51%), whereas less than 10% visit a psychiatrist. Even when the
      diagnostic is correct, the treatment prescribed is not systematically relevant.
      The treatment is, for example, frequently proposed for a too short period, and
      sometimes the prescribed product does not have proven antidepressive efficacy.
      Furthermore, as incorrect informations are frequently given to patients, and as
      there is a general biased judgement about psychotropic drugs in the general
      population, the compliance is usually poor for antidepressive treatment.
      Therefore, only a small minority of depressed patients benefits from an adequate
      care. Public health information methodological asserts. To improve this
      situation, delivering simple and clear-cut recommendations cannot be considered
      as sufficiently effective, and public health interventions are required.
      Different programs improving the recognition of depressive disorders have already
      been tested in some countries with encouraging results. These programs are based
      on information campaigns given to the public, and the training of general
      practitioners about the management of depressive disorders. The "Defeat
      Depression" campaign in Great-Britain and the "National Depression Screening Day"
      in the United-States of America may represent informative examples. Restricting
      these programs to general practitioners only is frequently criticized, as this
      may reduce efficacy. A multilevel approach is crucial for the success of action
      programmes against depression, because synergistic effects can be expected. In
      Germany, the "Nurnberger Bundnis gegen Depression" project was based on four
      levels, and effectively reduced the suicide rate. These levels of action included
      "cooperation with GPs", such as training sessions based on video, and presence of
      a phone hotline, "public relations activities", "training sessions for
      multipliers", such as priests, social workers and media, and "special offers for
      high risk groups and self-help activities". In France, such a program is clearly
      required.

PMID- 16633287
TI  - [The costs of bipolar disorder].
AB  - INTRODUCTION: According to the estimates of the World Bank and the World Health
      Organization bipolar disorder is the sixth leading cause of handicap throughout
      the world. The burden of this disease is similar to the one of schizophrenia. But
      cost-of-illness studies are too seldom. Although preventive treatments of bipolar
      disorder are available for more than fifty years, their economic impact has
      rarely been studied. LITERATURE FINDINGS: This review shows that the yearly cost
      of bipolar disorder is between 10,000 and 16,000 euro (12,000 and 18,000 US
      dollars). Eighty percent are indirect costs, 15% are linked to hospitalization
      and 5% to drugs. Hospitalization costs are lower in Health Maintenance
      Organization or general population studies than in studies performed on
      populations receiving care from psychiatric institutions or with a low socio
      economic status. DISCUSSION: The use of mood stabilizers has a substantial impact
      on direct costs which are halved and consequently on indirect costs. But
      different surveys all agree on the dramatic under-use of mood stabilizers which
      may be adequately prescribed to only a quarter of bipolar patients. CONCLUSION:
      Therefore, the optimization of mental health system resources should prompt
      incentives to better screen, diagnose, and treat patients with a bipolar
      disorder.

PMID- 16633288
TI  - [Effects of listening to previously hallucinated words by schizophrenia patients
      in remission: a functional magnetic resonance imaging study of six cases].
AB  - BACKGROUND: Despite immense importance of auditory verbal hallucinations (AVHs)
      in the phenomenology of schizophrenia, the neurocognitive and neurophysiological
      bases of AVHs remain obscure. On the neurocognitive level, it has been proposed
      that AVHs arise from the disordered monitoring manifested by patients' inability
      to recognize their inner speech as being their own. On the neurophysiological
      level, the AVHs have been attributed to the aberrant activity in the primary
      auditory cortex (Heschl's gyrus). Although interesting, these models cannot
      account for the very specific and restricted content of AVHs in individual
      patients. The specific content of AVHs persists across different psychotic
      episodes even after extended periods of remission. Furthermore, the AVHs are
      usually triggered by emotionally charged and stressful situations. DESIGN: We
      hypothesized that even during absence of AVHs, when patients are in remission,
      the verbal content remains present in the latent, pre-clinical form. In order to
      elucidate potential cerebral substrates of the dormant AVHs content, we employed
      functional magnetic resonance imaging (fMRI) in 6 schizophrenia patients in total
      remission of AVHs for at least 12 months, during listening to the words
      hallucinated by them in the past. Specifically, we created the list of previously
      hallucinated words for each patient and matched the words in terms of length,
      structure, emotional valence, semantic category and frequency of usage with the
      non-hallucinated words. Moreover, each patient was paired demographically with
      the control participant who was presented with the same words. We predicted that
      exposure to the hallucinated versus non-hallucinated words would result in
      increased activation in cerebral areas associated with cognitive and emotional
      content of previously experienced AVHs in patients, whereas the same comparison
      will not produce any significant changes in blood oxygen level-dependent (BOLD)
      signal in control participants. In addition, based on existing neuroimaging data
      obtained during experience of AVHs, we hypothesized that previously hallucinated
      words may elicit greater activation in the primary auditory cortex than the non
      hallucinated words in patients. Each pair of participants was analyzed
      separately. RESULTS: The most consistent finding in patients, absent in all
      control participants, was significant activation in the orbitofrontal and medial
      prefrontal cortex (PFC) during listening to previously hallucinated versus non
      hallucinated words. The orbitofrontal and medial PFC are both part of
      corticolimbic system and play an important role in cognitive control of emotion
      processing. DISCUSSION: Thus, present results imply that previously hallucinated
      words, even in remission, are associated with inappropriate emotional response on
      neurophysiological level in schizophrenia patients. The relative hyperactivation
      of orbitofrontal and medial PFC in patients may stem from and/or may contribute
      to anomalous neural plasticity and disordered connectivity in the corticolimbic
      circuitry. This in turn could lead to attribution of excessive emotional salience
      to normally neutral stimuli and over time via process of sensitization could
      result in hallucinations. Potential normalization of this dysfunction could
      reduce patients' susceptibility to experience AVHs in stressful situations. In
      addition to observed hyperactivations in the PFC, some schizophrenia patients
      exhibited anomalous BOLD signal in other regions of the corticolimbic system such
      as anterior cingulate gyrus and parahippocampal gyrus. These additional anomalies
      could be related to greater affective sensitivity to the hallucinated versus non
      hallucinated words in some patients. CONCLUSION: Finally, in contrast to our
      initial hypothesis we did not observe any significant differences between
      processing of the hallucinated versus non-hallucinated words in the primary
      auditory cortex. In retrospect, this result is not surprising because patients
      did not experience internally generated AVHs while in the scanner, but instead
      were exposed exclusively to externally generated stimuli.

PMID- 16633289
TI  - [Frequency of obsessive compulsive symptoms and disorder in patients with
      schizophrenia: importence for prognosis].
AB  - OBJECTIVE: The objective is to study the comorbidity rate of obsessive compulsive
      disorder and obsessive compulsive symptoms in patients with schizophrenia and
      their relation with the course of this illness. DESIGN: 73 out-patients from
      Istanbul Medical Faculty Department of Psychiatry and 4th Unit of Bakirkoy Mental
      Hospital who met the DSM III-R criteria for schizophrenia were recruited for this
      study. Other inclusion criteria were being out of acute exacerbation phase of
      schizophrenia. Yale-Brown Obsessive-Compulsive Scale, Yale Brown Obsessive
      Compulsive Symptom Screening Inventory were applied to patients. RESULTS:
      Comorbidity rate of obsessive-compulsive disorder in patients with schizophrenia
      was 9.6%, and also obsessive compulsive symptoms were detected 31% of patients.
      Aggressive obsessions were seen most frequently. These symptoms were also
      reported more frequently in the patients whose Global Assessment of Functionality
      score was higher than 45 points. Suicide attempts in psychiatric history were
      significantly higher for patients with obsessive-compulsive symptoms. CONCLUSION:
      Our findings indicate that obsessive-compulsive symptoms are seen more frequently
      than previously reported, and have no major effect upon the course of
      schizophrenia.

PMID- 16633290
TI  - [Validation of the QFS measuring the frequency and satisfaction in social
      behaviours in psychiatric adult population].
AB  - INTRODUCTION: Although everyone working in routine mental health services
      recognizes the scientific and ethical importance to ensure that treatments being
      provided are of highest quality, there is a clear lack of consensus regarding
      what outcome domains to include, what measure of assessment to use and, moreover,
      who to question when assessing. LITERATURE FINDINGS: Since the fifties, social
      functioning is considered as an important dimension to take into account for
      treatment planning and outcome measuring. But for many years, symptoms scales
      have been considered as sufficient outcome measures and social functioning
      improvement expected on the basis of symptoms alleviation. As symptoms and social
      adjustment sometimes appear relatively independent, no accurate conclusion
      concerning the patient's social functioning can so be driven on the basis of his
      clinical symptoms. More attention has then been directed toward the development
      of instruments specifically intended to measure the extent and nature of social
      functioning impairments observed in most psychiatric syndromes. Many of these
      instruments are designed to be completed by caregivers or remain time consuming
      and difficult to use routinely. Presently, in clinical practice, there is a need
      to rely on simple and brief instruments considering patients'perspective about
      their social adjustment as a function of time. AIM OF THE STUDY: The aim of this
      study is to present a new instrument, the QFS, initially developed in order to
      assess social functioning in patients involved in group psychotherapy programs
      conducted in a specialist mental health setting, as well as its psychometric
      characteristics. METHODOLOGY: It was designed to be completed in less than 10
      minutes and the questions are phrased in a simple and redundant way, in order to
      limit problems inherent to illiteracy or language comprehension. The QFS is a 16
      items self-report instrument that assesses both the frequency of (8 items) and
      the satisfaction with (8 items) various social behaviours adopted during the 2
      weeks period preceding the assessment. It yields three separate indexes of social
      functioning, defined a priori and labelled "frequency", "satisfaction" and
      "global". The higher the scores, the better the social functioning. The QFS was
      administered to 457 subjects, aged between 18 and 65, including 176 outpatients
      (99 with anxious or depressive disorders, 25 with personality disorders and 52
      with psychotic disorders) and 281 healthy control subjects. RESULTS: No
      significant difference was found between patients and controls according to age
      or gender distribution. Acceptance rate was high (>95%). Moreover, the QFS was
      generally acceptable to the clinicians who used it. Internal consistency
      calculated for each index ranged from 0.65 to 0.83 (Cronbach alpha). Test-retest
      reliability, calculated within a 15 days time interval on a sample of 49 healthy
      controls, ranged from 0.69 to 0.71 (intraclass correlation coefficient).
      Discriminant validity was calculated on healthy controls and patients divided
      into sub-groups according to their diagnosis. It showed to be excellent, with
      significantly higher scores in control subjects than in psychiatric patients and
      significant differences across diagnostic categories (Kruskal-Wallis ANOVA with
      post-hoc tests, all p<0.05). The convergent validity of the QFS with other
      measures of social functioning was calculated, using the Social Adaptation Self
      Evaluation Scale (SASS) and the Social Adjustment Scale Self-Report (SAS-SR).
      With the SASS, the convergent validity was higher among patients (Spearman rS
      0.71 to 0.92, p<0.01) than controls (rS from 0.49 to 0.66, p<0.001). In healthy
      controls, correlation with the SAS-SR was moderate but statistically significant
      (rS from - 0.21 to - 0.44, p<0.05). When comparing QFS scores with self-rated
      symptoms severity, lower levels of social functioning were significantly
      associated with more severe symptoms according to the Brief Symptom Inventory
      (BSI: rS from - 0.38 to - 0.65, p<0.001). The QFS indexes demonstrated
      sensitivity to change (Wilcoxon: all p<0.05) on a sample of 27 out-patients
      suffering from anxious-depressive disorders questioned before and after 4 months
      of cognitive behavioural group therapy running on a weekly basis during 16
      sessions of 2 hours each.The factorial validity of the QFS was measured through 3
      separate factor analysis conducted using the data of 457 subjects. The first
      analysis considered only Frequency items; 7 out of 8 items had loadings above 0.5
      on Factor 1 accounting for 30.7% (unrotaded) of the variance. The second analysis
      considered only Satisfaction items; all items had loadings above 0.6 on Factor 1
      explaining 43.4% (unrotaded) of the variance. And finally, in the third factor
      analysis, all QFS items were included; 15 out of 16 items had loadings above 0.4
      on Factor 1 accounting for 30% (unrotated) of the variance. Concerning the
      factorial validity of the instrument, these results suggest that all QFS items
      belong to the same underlying dimension. DISCUSSION: Finally, provisional norms
      for the QFS are provided for healthy controls, in order to characterise
      individual patients or patient subgroups. In conclusion, the need for assessment
      in clinical routine, in order to estimate different aspects of patients
      conditions as well as the quality of the treatment provided, has contributed to
      the development of a large variety of instruments measuring several domains.
      Concerning the level of social functioning, many instruments fail to meet chief
      criterion of feasibility, remaining often too complex or time onsuming. Moreover,
      only few of them are available in French. CONCLUSION: The QFS presented here is a
      brief, simple and easy to administer self-rating scale that displays satisfactory
      psychometric properties. It seems to be a valuable instrument for the monitoring
      of social functioning in psychiatric patients which, from a therapeutic point of
      view, may have a clear impact as it sets up expectation of change and allows both
      to reality test patients and therapists beliefs about the presence of progress or
      not and to identify if therapy is working on this specific outcome domain.
      Though, to date, the administration of the QFS to other populations and treatment
      modalities requires further investigation.

PMID- 16633291
TI  - [Brothers of children with a neurological disease: difficulties and affective
      needs. Study of a clinical sample].
AB  - INTRODUCTION: Feelings of envy and jealousy among brothers belonging to families
      with a child affected by a chronic neuromotor impairment have rarely been studied
      and literature on this subject is sparce. The interest of this work arises in
      particular from our experience with families and children suffering from this
      kind of disability. AIMS OF THE STUDY: The individuation of frequency and
      characteristics of overt or "hidden" emotional problems in brothers of
      handicapped children. Needs of the handicapped child lead to the partial
      disinvestment of the "healthy" one. We therefore focused our attention on the
      defensive mechanisms involved. METHOD: The work was carried out in the
      Rehabilitation Unit of our Department of Child Neuropsychiatry. We selected all
      the families in which a son exhibited severe neuromotor impairment, and we
      proposed some sessions with the parents and the healthy children. Only 10
      families with 11 children accepted these sessions. We asked the other families to
      fill-in the Achenbach checklist (CBCL). Assessment of the 11 children seen was
      made with talks, drawing and playing sessions, and with an interview of the
      parents at the beginning and at the end of the sessions. RESULTS: We present the
      data of 33 CBCL filled-in and returned and of 11 psychodiagnostic observations.
      The CBCL showed 6 pathological and 5 borderline (with high psychopathological
      risk) total T scores. Among the 11 clinically observed children, 4 revealed a
      relevant psychopathological profile, so an individual psychotherapeutic therapy
      was proposed. These children expressed their emotional problems by difficult peer
      relationships, attention and concentration deficits and failure at school.
      Moreover, we found a significant correlation between a relevant child
      psychopathology, the fragile personality structure of the parents, and problems
      in the parental couple. CONCLUSIONS: These data stress the importance that must
      be given to emotional problems of handicapped children's brothers. Very often
      these children aren't able to express these problems, because either the parents'
      mental space is full of fears for the sick child's prognosis and care, and their
      "free" time is filled with hospitalisations, check-ups and rehabilitation. Our
      experience shows that giving attention and space for thoughts encourages
      emotional and relational movements, with a transforming value that leads to
      enhanced integration of emotional experiences.

PMID- 16633292
TI  - [Memory, brain, a machine for learning and rememberingy].
AB  - Following a previous paper describing how memory appeared in the nervous system
      in mammalians, during evolution, and how its significant growth led to
      hominization, the present paper intends to show the prevailing place it occupies
      in human brain. Memory, an attribute of cortex, is an engraving of neuronal
      circuits created during information analysis of data input in the cortex. It is
      created either by repetition of information or by increase in brain activity,
      under the influence of a central brain system. In the brain of human newborns,
      immature and unprogrammed, but endowed with a great capacity for learning, the
      whole organization and programming will be possible through learning and
      remembering. Communication pathways between functions are memory pathways. Brain
      becomes a memory machine and every cortical area is a memory territory. Its
      lesion results in a disturbance corresponding exactly to forgetting what has been
      stored in that territory.

PMID- 16633293
TI  - [Schizophrenia and semantic priming effects].
AB  - INTRODUCTION: This article is a review of studies using the semantic priming
      paradigm to assess the functioning of semantic memory in schizophrenic patients.
      CONTEXT: Semantic priming describes the phenomenon of increasing the speed with
      which a string of letters (the target) is recognized as a word (lexical decision
      task) by presenting to the subject a semantically related word (the prime) prior
      to the appearance of the target word. This semantic priming is linked to both
      automatic and controlled processes depending on experimental conditions (stimulus
      onset asynchrony (SOA), percentage of related words and explicit memory
      instructions). Automatic process observed with short SOA, low related word
      percentage and instructions asking only to process the target, could be linked to
      the "automatic spreading activation" through the semantic network. Controlled
      processes involve "semantic matching" (the number of related and unrelated pairs
      influences the subjects decision) and "expectancy" (the prime leads the subject
      to generate an expectancy set of potential target to the prime). These processes
      can be observed whatever the SOA for the former and with long SOA for the later,
      but both with only high related word percentage and explicit memory instructions.
      LITERATURE FINDINGS: Studies evaluating semantic priming effects in schizophrenia
      show conflicting results: schizophrenic patients can present hyperpriming
      (semantic priming effect is larger in patients than in controls), hypopriming
      (semantic priming effect is lower in patients than in controls) or equal semantic
      priming effects compared to control subjects. DISCUSSION: These results could be
      associated to a global impairment of controlled processes in schizophrenia,
      essentially to a dysfunction of semantic matching process. On the other hand,
      efficiency of semantic automatic spreading activation process is controversial.
      These discrepancies could be linked to the different experimental conditions used
      (duration of SOA, proportion of related pairs and instructions), which influence
      on the degree of involvement of controlled processes and therefore prevent to
      really assess its functioning. In addition, manipulations of the relation between
      prime and target (semantic distance, type of semantic relation and strength of
      semantic relation) seem to influence reaction times. However, the relation
      between prime and target (mediated priming) frequently used could not be the most
      relevant relation to understand the way of spreading of activation in semantic
      network in patients with schizophrenia. Finally, patients with formal thought
      disorders present particularly high priming effects relative to controls.
      CONCLUSION: These abnormal semantic priming effects could reflect a dysfunction
      of automatic spreading activation process and consequently an exaggerated
      diffusion of activation in the semantic network. In the future, the inclusion of
      different groups schizophrenic subjects could allow us to determine whether
      semantic memory disorders are pathognomonic or specific of a particular group of
      patients with schizophrenia.

PMID- 16633294
TI  - [Relations between alexithymia and anhedonia: a study in eating disordered and
      control subjects].
AB  - INTRODUCTION: Alexithymia and anhedonia both refer to a deficit in emotion
      regulation. Although these 2 concepts have been conceptualized to be closely
      linked, very few studies aimed at examining carefully their interrelations.
      OBJECTIVES: Therefore, the purpose of the present study was to investigate the
      relationships between scores on alexithymia and anhedonia self-reports, and to
      assess whether the results were influenced by the presence of an emotional
      disorder. LITERATURE FINDINGS: The 20-item Toronto Alexithymia Scale is the self
      report most frequently used to assess alexithymia. Nevertheless, the results of
      recent studies comparing the psychometric properties of the TAS-20 and another
      alexithymia self-report - the Bermond-Vorst Alexithymia Questionnaire (BVAQ) -
      have recommended the BVAQ over the TAS-20. DESIGN: Thus, both questionnaires were
      included in the present study. In addition, since depression and anxiety may
      influence the correlations between alexithymia and anhedonia scores, we also
      measured depression and anxiety and these scores were used to control for their
      potential confounding effect in the analyses. Two groups of participants were
      included in this study: 46 eating disordered female patients (ED) and 198 female
      control subjects. All the participants filled up the Bermond-Vorst Alexithymia
      Questionnaire-form B (BVAQ-B), the 20-item Toronto Alexithymia Scale (TAS-20),
      the Chapman and Chapman Social Anhedonia Scale (SAS) and Physical Anhedonia Scale
      (PAS), the 13-item Beck Depression Inventory (BDI) and the Spielberger State and
      Trait Anxiety Inventory (STAI-Y). The analyses consisted, first, in establishing
      the matrix of correlations between these self-reports total scores, using
      Pearson's coefficients of correlation. Then, TAS-20, BVAQ-B, SAS and PAS scores
      were correlated, adjusting for BDI and STAI scores, using partial correlation
      analyses. Mean scores comparisons according to the group of participants, and to
      the presence/absence of alexithymia, as well as to the presence/absence of
      anhedonia were performed using ANCOVAs or Mann-Whitney tests. RESULTS: As
      predicted, BDI and STAI scores were found significantly and positively correlated
      with alexithymia and anhedonia scores in both participant groups. After
      controlling for depression and anxiety scores, TAS-20 and PAS scores remained
      significantly correlated, but not TAS-20 and SAS scores. BVAQ-B scores remained
      significantly correlated with PAS and SAS scores in the control group, but only
      with the PAS scores in the ED group. ED patients had higher alexithymia and
      anhedonia scores than the controls. In total, among the alexithymic individuals,
      8.9% were social anhedonics, and 31.1% had a physical anhedonia. Conversely,
      among the participants with a physical anhedonia, two third were alexithymics.
      The same proportion of participants with a social anhedonia was alexithymic
      (66.7%). CONCLUSION: The results of the present study are informed about the
      relationships between alexithymia and anhedonia. They also stress the need to
      rely on several alexithymia measurements, and they further demonstrate the
      necessity to compare the associations between different affect regulation
      dimensions in normal and psychopathological disorders.

PMID- 16633295
TI  - [How can psychological help be provided for the patient/caregiver tandem home?].
AB  - INTRODUCTION: Elderly people and their family helpers are often isolated at home
      and do not have access to the professional psychological help that they require.
      For an elderly population, the trips to consulting rooms are difficult, tedious
      and expensive. Besides, maintaining a patient at home is heavy to manage for
      close relatives because of the organization, financial issues and above all the
      risk of psychological burnout. The literature shows us that psychological
      assistance is more common at distance from home, in hospitals, in special
      institutions or specific organizations. However, there is a clear need of help at
      home. We propose to develop psychological assistance at home for the
      patient/helper tandem in cases of dementia. This prospective study reports three
      different cases. METHOD: This study is a qualitative pilot study. Participants
      characteristics: patients were diagnosed with severe dementia, assistance showed
      deep fatigue of the helper, both members of the tandem lived at home, age above
      69 years, the eed for nursing care at home. THERAPEUTIC ASSESSMENT: The
      psychological clinician acts after proposing his helpand not on a clear request
      from the patient. He will meet his patient 7 times during 4 months. The meetings
      always take place in the same place and last 45 minutes. Confidentiality during
      the meeting is explained and guaranteed so the patient can speak openly.
      EVALUATION: An independent psychologist assessed the monitoring in the hospital.
      Our methodology included two assessments: the first, assessing the task of the
      helper before the evaluation and the second taking into account a new measurent
      of the task and the opinions of the participants following a semi-directed
      interview. The evaluation of the task was performed using Zarit's scale. The
      evaluation was also based on the clinical observation of the psychologist.
      RESULTS: Organization of the monitoring: one meeting per week was sufficient for
      all participants with a minimal duration of 45 minutes. The fact that the
      meetingsrook place at home was appreciated, because of their simple and
      convenient organization. The patient/helper tandems in those suffering from
      advanced dementia could only have taken place in the home because transport any
      where else would have beent too difficult for them. The sessions during this
      research study were free of charge. Two out of three participants were ready to
      pay so long as the study could continue. The managers were bothered a few times
      by phone calls and/or unexpected visits, invitations for a cup of tea and
      requests for a small service (like mailing a letter). Assistance for the
      caregiver: all the caregivers declared that assistance was a personal improvement
      in a period of doubt, loss of self-confidence and isolation. Furthermore,
      clinical observation of the therapeutic assistance appears to show that
      psychological help at home could lead to the improved psychological function of
      the helper. This was emphasized when we established the limits of the
      caregiver/patient relationship. We observed a better balance in the input of
      investing and de-investing and better acceptance of the identity modifications
      which were required for the caregiver. Assistance for the patient: we believe
      that this sort of intervention has positive effects on the patients themselves.
      This care at home protects the destructurated identity of the patients and their
      intimity. Moreover, intrapsychic tension can be lowered by being shared with the
      psychologist. Assessment of the burden: among the three patients who wete
      studied, the burden was unaltered in one case (43/88; 43/88), significantly
      improved in one case (41/88; 24/88) and remained light in one case (18/88;
      16/88). DISCUSSION: We discovered that Zarit's test showed some limits. The time
      to complete the test is quite long and tedious for caregivers. Some questions are
      too direct and can put the caregivers in a guilty position. The mini Zarit
      version with only seven items, appears more satisfactory because it's shorter and
      provokes less guilt. The other point concerns the therapeutic frame at home. The
      usually represents all the constants of the therapeutic process including the
      role of the psychologist and all the items that refer to space, time, management
      of the timetable, payement and interruptions in care. Could the fact of being at
      home be harmful for the therapeutic process? Of course, the place of residence is
      less neutral than a office in an institution and the superposition of the frame
      of life and of the therapeutic frame raises lots of questions for the
      psychologist: entering a private house is like entering a private life, which is
      not without consequences on the follow-up. We are here far from a classical frame
      of therapeutic interviews, so the frame must be clearly defined. CONCLUSION: This
      prospective study leads us to the conclusion that the superposition of the frame
      of life and of the therapeutic frame represents a limit to psychotherapy but is
      not exclusive of psychological support at home. As a supplement to this face to
      face follow up at home, we could imagine other ways of providing such
      psychological support, by phone or by telemedicine for instance. Could the new
      technologies of communication help to compensate the lack of means in favour of
      the caregivers at home? Although these new technologies are more dedicated to
      institutions than to providing care at home, could they not be helpful for
      organizing psychological help at home? However, in order to validate such
      devices, they need to be fried and assessed at home.

PMID- 16633296
TI  - [Atypical antipsychotics and sexual dysfunction: five case-reports associated
      with risperidone].
AB  - LITERATURE FINDINGS: Sexual and reproductive function side effects of atypical
      antipsychotics are frequent, often underestimated and badly tolerated. They
      contribute to the 50% rate of non-compliance reported for treated patients.
      Prevalence of sexual dysfunction associated with atypical antipsychotic treatment
      is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much
      better than typical antipsychotics, and among them, risperidone seems to induce
      more and quetiapine less sexual dysfunction. Most atypicals are non-selective,
      and have actions on multiple central and peripheral receptors. Among these,
      dopaminergic blockade could have a direct - altering motivation (desire) and
      reward (orgasm) - and an indirect negative influence on sexuality. Actually, the
      secondary hyperprolactinemia induced by some antipsychotics (typical
      antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced
      for female patients, and may have a detrimental effect on sexual function. It
      also may result in hypogonadism, particularly for female patients. The long-term
      consequences of this secondary hypogonadism are subject to debate but potentially
      severe. Furthermore, the blocking and/or modulating actions of atypical
      antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors
      all have the potential to contribute to secondary sexual problems. The
      pharmacological profile of risperidone, characterized by a strong affinity for D2
      and alpha1 receptors, correlates with his tendency to significantly elevate
      prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We
      describe five case-reports of sexual or hormonal disturbances associated with
      risperidone treatment: two cases of ejaculatory disturbance, one case of
      galactorrhea and two cases of amenorrhea. Alberto and David are two young male
      schizophrenic patients, treated with risperidone, and complaining of a total
      absence of ejaculation despite a preserved orgasm. Many recent case-reports
      describe the occurrence of retrograde ejaculation associated with risperidone but
      the exact prevalence is unknown. Retrograde ejaculation is thought to be related
      to the strong adrenolytic activity of risperidone. Alberto refused his medication
      because the ejaculatory dysfunction was unbearable for him. A switch to
      haloperidol depot was eventually well tolerated, without any sexual complaints.
      His case emphasizes the importance of sexual function for self-esteem and how
      this may amplify the intolerance to side-effects. David is on depot-risperidone
      in a setting of a legally forced treatment. Though he - reluctantly - accepts his
      medication, this side effect exacerbates his pre-existing delusions, strongly
      focused on sexual themes. His case illustrates how intolerance to sexual side
      effects may be amplified by nature of delusions. Mireille is a 58 year old
      psychotic female patient, whose 2 mg risperidone treatment produced a unilateral
      galactorrhea. This sign became problematic because potentially visible at a time
      when Mireille started an activity in a sheltered occupation in town. Lowering
      dosage of antipsychotic allowed disappearance of the problem. Subjective
      responses to galactorrhea have been reported to be highly individual. Apart being
      a potentially visible side-effect, it may be misinterpreted as evidence of
      pregnancy or of a tumoral process. The cases of Ermina and Denise illustrate two
      contrasted situations in terms of subjective tolerability of reproductive
      function side-effects. Both were pre-menopausal patients with hyperprolactinemia
      secondary to risperidone treatment, resulting in amenorrhea. This was unbearable
      for Ermina. A switch to olanzapine allowed, one month later, the menses to
      resume. For Denise, on the other hand, the amenorrhea was a positive event,
      freeing her of unpleasant menses. DISCUSSION: Amenorrhea occurs in about 30% of
      pre-menopausal women treated with risperidone. It is a consequence of
      hyperprolactinemia, which, although often silent, is not devoid of potential
      negative consequences (ie increased risk of osteoporosis or neoplasia, worsening
      of psychopathology) (34). When hyperprolactinemia is symptomatic, lowering of the
      dose of the antipsychotic, or switching to a prolactin-sparing agent (olanzapine,
      quetiapine, aripiprazole and clozapine) is recommended. Before this, women with
      amenorrhea secondary to antipsychotic-induced hyperprolactinemia should be
      advised that menses may resume. Especially after long-standing amenorrhea they
      may assume being menopaused, hence may believe birth control measures are no
      longer required. The prevalence of antipsychotic-induced sexual and reproductive
      function side-effects is high. Clinicians should be aware of them, because they
      are often badly tolerated, are associated with a low satisfaction and may
      therefore result in low adherence with treatment. This implies for the clinician
      to overtly discuss with the patient of his sexuality and the potential negative
      impact of antipsychotic treatment on it. The recognition of these problems allows
      the searching together for a solution. CONCLUSION: The described cases indicate
      that solving the problem is often possible, provided that individual preferences
      and subjective impact are taken in account. Antipsychotic treatment is often
      prescribed for very long periods. A better knowledge of - and attention to - the
      associated side effects, particularly on the sexual and reproductive functions,
      is necessary in order to reduce some potentially negative long-term effects and
      to improve the adherence to treatment of our patients.

PMID- 16633297
TI  - [Clinical and therapeutic characteristics of social phobia in French psychiatry
      (Phoenix study)].
AB  - Only few clinical epidemiologic studies have been conducted on social phobia in
      France to date. It is however a frequent disorder, with often severe alteration
      of social adaptation and quality of life, and for which effective treatments
      exist. Thus, it seems really important to further explore how these patients are
      nowadays identified and treated in psychiatry. It was the objective of the
      Phoenix study. In this observational multi-center study, 952 psychiatric in- or
      out-patients, with a primary diagnosis of social phobia according to DSM IV
      criteria, were included. Numerous diagnostic and psychometric evaluations were
      carried out, in order to evaluate the comorbidity (Mini International
      Neuropsychiatric Interview, Hospital Anxiety and Depression Scale), the intensity
      of social anxiety (Liebowitz Social Anxiety Scale), and various aspects of the
      functional and emotional impact (Various Impact of Social Anxiety scale, Sheehan
      Disability Scale, SF-36, Positive and Negative Emotionality scale). The patients
      were in majority females (57.6%), with a mean age 37.5 years, and with a mean
      duration of social anxiety disorder 12.5 years. The mean scores of social anxiety
      on Liebowitz scale was 40.3 +/- 12.6 for the fear factor, and 38.3 +/- 13.6 for
      the avoidance factor. The generalized social anxiety subtype (anxiety in most
      social situations) was present in 67.8% of the patients. A major depressive
      disorder was found in 47.7% of the sample, and the prevalence of agoraphobia was
      even higher (49.2%). As known in clinical practice and in other studies, the
      prevalence rates of current alcohol dependence and substances abuse were also
      important in this population (respectively 10.6% and 12.7%). Mean scores of the
      Hospital Anxiety and Depression (HAD) sub-scales were 13.9 +/-3.8 for anxiety and
      9.1 +/-4.5 for depression. About 15% of the patients had a history of suicide
      attempt, and a suicidal risk was present in nearly 40% of the sample. The
      psychosocial impact and the alteration of quality of life (with especially a poor
      physical health perception) were very significant, in the family, educational or
      occupational and social domains. Mean scores of the Sheehan Disability Scale were
      6.1 +/- 2.6 for professional impairment, 5.0 +/- 2.7 for familial impairment, and
      6.6 +/- 2.3 for social life impairment. In addition to the disability due to
      social phobia intensity, an important part of the burden was due to depressive
      symptoms. Approximately 60% of the patients had already a psychiatric treatment
      at the time of the survey (since 1,7 years in average), but only 17% had a
      cognitive behavioral therapy (CBT), and 48% had an antidepressant treatment.
      These proportions increased in a significant way after the consultation during
      which the investigation was carried out: an antidepressant was prescribed to 72%
      of the patients, and a CBT is proposed to 48%. On the whole, this study confirmed
      the severity and the morbidity of social phobia in a very large sample of French
      psychiatric patients. The depressive disorders, suicidal risk, and social
      impairment associated with this condition should incite to more detect and treat
      it. Seeing the long duration of the disease in our sample, and the lack of
      specific therapies in many cases, the identification and the treatment of social
      phobia must be improved, and the role of the psychiatrists in this process seems
      very important.

PMID- 16633298
TI  - [The evaluation of professional practices and their use in
      hepatogastroenterology].

PMID- 16633299
TI  - Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic
      adenocarcinoma. Results of a phase II trial.
AB  - BACKGROUND: The efficacy and benefit of second-line chemotherapy in advanced
      pancreatic adenocarcinoma has never been demonstrated although it is regularly
      used. PATIENTS AND METHODS: A randomized phase II study evaluating oxaliplatin
      alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional
      5-FU combination (OXFU) in untreated advanced pancreatic adenocarcinoma has been
      conducted. In this trial, a second-line treatment with the OXFU regimen (OXA 130
      mg/m2 2-h intravenous (i.v.) infusion combined with 5-FU (1000 mg/m2/day,
      continuous i.v., days 1-4), every 3 weeks) was offered to patients progressing
      after single agent treatment. RESULTS: Eighteen out of 32 patients (12 males,
      median age 57 years) treated in the single agent arms received the OXFU
      combination in second-line treatment. WHO performance status was at least 2 in
      61% of the patients. There was no objective response and 3 patients (17%) had a
      disease stabilisation. Median time to progression from the start of second-line
      treatment was 0.9 months. Median overall survival was 4.9 months from the start
      of front-line therapy and 1.3 months from the start of second-line therapy.
      CONCLUSION: The results of this trial bring arguments to support a modest value
      of second-line chemotherapy for advanced pancreatic adenocarcinoma.

PMID- 16633300
TI  - Gastroesophageal reflux disease in primary care. Prevalence, epidemiology and
      Quality of Life of patients.
AB  - AIM: To determine the prevalence of typical symptoms of gastroesophageal reflux
      disease in a large group of patients consulting their general practitioners (GP)
      for diverse reasons, as well as the quality-of-life (QoL) of patients with such
      symptoms. PATIENTS AND METHODS: During the same day, participating GPs (N=3 200)
      systematically asked all of their patients about the presence of heartburn and
      regurgitation. For all patients who responded positively, the GPs filled in a
      questionnaire and the patient a specific QoL questionnaire. RESULTS: Among 40 982
      patients attending GP consultations, 4 124 (10.1%) had one or both symptoms.
      Prevalence was higher in men (11.1%) than in women (9.3%, P<0.001), and increased
      with age up to 50-59 yrs then slowly declined. Symptoms were present on a weekly
      basis in 72.8% of patients. Smoking, frequent or nocturnal occurrence of
      symptoms, regurgitation, and esophagitis were significantly linked up with a
      higher occurrence of extra-digestive symptoms (cough, ENT symptoms, chest pain).
      QoL declined with increasing frequency of symptoms, which especially affected
      food intake, psychology, well-being and daily life. CONCLUSION: In France,
      typical symptoms of gastroesophageal reflux disease are observed in 10% of the
      adult population, and markedly alter their QoL.

PMID- 16633301
TI  - Assessment of patient satisfaction with endoscopy using an interactive voice
      response system.
AB  - AIM: The aim of this study was to determine the feasibility of patient's
      satisfaction assessment after endoscopy using an interactive voice response (IVR)
      system. METHODS: A specific IVR system was developed for this study and proposed
      to patients by 161 private gastroenterologists after an endoscopic procedure. No
      reminder was used for the patients not calling spontaneously the IVR. RESULTS:
      After endoscopy, 31% of the patients called the IVR and 1052 answered the entire
      questionnaire. The answers obtained by the IVR and a face-to-face interview were
      concordant for 98.8% of the questions. The endoscopy was carried out with
      anesthesia for 94% of the patients and 95% stated they would agree to undergo the
      procedure again under the same conditions. This was independently associated with
      the presence of explanations about the procedure before its realization, male
      gender and, for the patients having had a colonoscopy, difficulties in taking the
      bowel cleaner and the presence of pain after the colonoscopy. CONCLUSION: This
      study shows the feasibility of patient's satisfaction assessment with endoscopy
      using an IVR system under routine conditions of endoscopy practice.

PMID- 16633302
TI  - Peritoneal tuberculosis in the Fes University Hospital (Morocco). Report of 123
      cases.
AB  - AIMS: Peritoneal tuberculosis is an important public health issue in Morocco. Our
      aim was to describe the clinical, biological, and therapeutic features of
      peritoneal tuberculosis treated in a University Hospital in Morocco. PATIENTS AND
      METHODS: We retrospectively included 123 patients with peritoneal tuberculosis
      diagnosed at the gastroenterology unit of the Fes University Hospital between
      January 2001 and August 2003. RESULTS: The mean age was 28 years with a clear
      female predominance (sex ratio 2.61). Ascites associated with fever were the most
      frequent signs found in 80.5% of patients. The ascitic fluid was exsudative in
      90% of cases and lymphocytic in 88%. The diagnosis was based on laparoscopy or
      laparotomy with peritoneal biopsy demonstrating caseating granulomatous lesions
      in 92.4% of patients. Patients were given antituberculous therapy for 6 months,
      and the outcome was favourable in 90%. CONCLUSION: Peritoneal tuberculosis is
      very frequent in Morocco, where the diagnosis is based exclusively on peritoneal
      biopsies obtained during laparoscopy. With an adapted treatment, the course of
      the disease is favourable in most cases.

PMID- 16633303
TI  - [The solitary rectal ulcer syndrome].
AB  - The solitary rectal ulcer syndrome is a rare debilitating disorder of the rectum
      characterized by perianal chronic pain with passage of blood and mucus. The
      pathogenesis remains uncertain, rectal prolapse and trauma from straining are the
      main hypothesis. The diagnosis includes clinical symptoms associated with
      endoscopic lesion (erythema, ulcer or polypoid lesion) and histological features.
      Mano-metric studies and defecography are helpful to determinate an underlying
      defecation disorder or rectal prolapse. The treatment is controversial including
      a conservative option (medications and behavioural therapy) with poor long term
      results, and the surgical option (treatment of a rectal prolapse with or without
      resection of the lesion), more aggressive with uncertain results in a long follow
      up period.

PMID- 16633304
TI  - [Persistent abdominal pain].

PMID- 16633305
TI  - [Diagnosis of dysphagia with no apparent cause].

PMID- 16633306
TI  - [Management of functional dyspepsia].

PMID- 16633307
TI  - [Management of a patient with functional diarrhea].

PMID- 16633308
TI  - [Management of elevated pancreatic enzymes discovered by chance].

PMID- 16633309
TI  - [Diagnosis and treatment of dyschezia].

PMID- 16633310
TI  - [Are reagent strips useful for the diagnosis of spontaneous bacterial
      peritonitis?].

PMID- 16633311
TI  - [Can we improve hepatitis B vaccination coverage in HIV-infected persons?].

PMID- 16633312
TI  - Diagnostic value of two reagent strips (Multistix 8 SG and Combur 2 LN) in
      cirrhotic patients with spontaneous bacterial peritonitis and symptomatic
      bacterascites.
AB  - OBJECTIVE: Spontaneous bacterial peritonitis is a life-threatening complication
      in patients with liver cirrhosis requiring a rapid diagnosis. We have tested two
      reagent strips, Multistix 8 SG and Combur 2 LN for bedside diagnosis of
      spontaneous bacterial peritonitis and symptomatic bacterascites, a variant of
      spontaneous bacterial peritonitis. METHODS: Responses of the two strips in
      colorimetric scale were compared with results given by cyto-bacteriological
      analysis of ascitic fluid. Results with positivity in grades 1 and 2 of
      colorimetric scale were analyzed. RESULTS: Four hundred and forty three
      paracentesis were performed in 116 patients including 46 samples of ascitic fluid
      with spontaneous bacterial peritonitis occurring in 25 patients and 20 samples of
      ascitic fluid with symptomatic bacterascites occurring in 17 patients. Forty two
      percent of spontaneous bacterial peritonitis were culture-negative neutrocytic
      ascites, gram-positive pathogens and enterobacteriaceae were responsible for 36%
      and 21% episodes of spontaneous bacterial peritonitis and 71% and 29% episodes of
      symptomatic bacterascites respectively. Fifty seven percent of spontaneous
      bacterial peritonitis had polymorphonuclear cell count<1000/mm3. For spontaneous
      bacterial peritonitis diagnosis, grade 1 positive Multistix and Combur tests had
      a sensitivity of 69.6% and 80.4% respectively, and a negative predictive value of
      96% and 97.3%. Grade 2 positivity increased specificity to 98% and 99.2% and
      positive predictive value to 75% and 91% for the two strips respectively. Grade 1
      positive tests had a sensitivity of 100% and 90% and a negative predictive value
      of 100% and 99.4% respectively for diagnosis of spontaneous bacterial peritonitis
      with polymorphonuclear count > 1000/mm3. For symptomatic bacterascites diagnosis,
      grade 1 positive tests had a sensitivity of 22.4% and 44.4% respectively and a
      negative predictive value of 96% and 97%. CONCLUSION: Although Combur had a
      higher sensitivity than Multistix for the diagnosis of spontaneous bacterial
      peritonitis, sensitivity of the two strips remains low with polymorphonuclear
      cell count<1000/mm3. Grade 2 positive Combur test had an acceptable positive
      predictive value. Sensitivity of both strips is insufficient for diagnosis of
      symptomatic bacterascites. Rapid cyto-bacteriological analysis of ascitic fluid
      remains necessary for diagnosis of these complications.

PMID- 16633313
TI  - Liver repopulation trial using bone marrow cells in a retrorsine-induced chronic
      hepatocellular injury model.
AB  - OBJECTIVES: The aim of this study was to determine the potential of bone marrow
      derived cells to participate in liver repopulation. In this model, the injected
      cells had a "selective growth advantage" compared to the native hepatocytes whose
      proliferation was blocked by retrorsine. METHODS: Total bone marrow cells were
      isolated from male Fisher 344 rats not deficient in dipeptidyl peptidase activity
      (F344, DPP IV+). The animals were given an injection of retrorsine and were
      divided in 2 groups: 1/group R (N=13): female F344 rats received 4.106 male cells
      at day 0 (labeled by chromosome Y). 2/group RH (N=19): Male F344 DPP IV- rats
      received 4.106 male DPP IV+ cells after hepatectomy at day 0 (labelled by DPP IV
      activity). RESULTS: Group R: no male cell was detected by PCR at day 14, 28, 56
      and 84. Group RH: isolated DPP IV+ transplanted cells were observed at days 14
      and 28 in the periportal areas. Later, these cells were no longer visible. Liver
      regeneration occurred by proliferation of small clusters of hepatocytes.
      CONCLUSIONS: In this experimental model the capacity of transplanted bone marrow
      cells to repopulate the liver was tested against the same capacity of native
      liver stem cells. Liver regeneration occurred via native liver cells seen as
      small hepatocytes. In this model the small hepatocytes may be considered as
      hepatic stem cells.

PMID- 16633314
TI  - [Intestinal permeability and cirrhosis].
AB  - Patients with cirrhosis are at increased risk of developing infections due to
      bacterial translocation. This process depends on three principal factors:
      bacterial overgrowth, immunodepression, and altered intestinal permeability.
      Intestinal barrier functions may be disturbed in cirrhosis, related to the toxic
      effects of alcohol (on mucosa and biological membranes) and portal hypertensive
      enteropathy. Few studies on the assessment of intestinal permeability in
      cirrhotic patients are available, and contradictory results may be explained by
      methodological differences. However, four studies using a differential sugar
      absorption test (lactulose-mannitol test, a combination of an oligosaccharide and
      a monosaccharide) showed an increased intestinal permeability in cirrhotic
      patients. The recurrence of spontaneous bacterial peritonitis can be appreciated
      only by one similar case history, a low rate of protides in ascites (<10 g/L),
      bilirubinemia > 55 micromol/L, and thrombocytopenia<98.000/mm3. These results
      suggest that primary antibiotherapy prophylaxis should be recommended, but this
      recommendation is limited by the risk of bacterial resistant selection and by the
      fact that no patient survival benefits was shown. Intestinal permeability could
      be another predictive factor to justify preventive antibiotherapy; but more
      studies are needed and methods should be standardized (technique used to measure
      permeability, patient groups involved).

PMID- 16633315
TI  - [A case report of stromal tumor in the ligamentum teres hepatis].
AB  - This case report relates to a 73-year old man presenting a large susmesocolic
      abdominal tumor whose analysis demonstrated to be a stromal tumour of the
      ligamentum teres hepatis.

PMID- 16633316
TI  - [Anal metastasis from a lung cancer].
AB  - We report an anal metastasis from a lung cancer which was diagnosed on symptoms
      mimicking an acute anal abcess. The diagnosis was based on specific
      immunohistochemistry.

PMID- 16633317
TI  - [Progressive multifocal leukoencephalopathy secondary to JC virus infection after
      liver transplantation and treatment of recurrent hepatitis C].
AB  - Progressive multifocal leucoencephalopathy due to JC virus is a rare complication
      of liver transplantation. Only four cases have already been described in the
      literature. This disease is difficult to differentiate from leucoencephalopathy
      associated with immunosuppressive drugs such as cyclosporin or tacrolimus.
      Positive diagnosis of progressive multifocal leucoencephalopathy no longer
      requires cerebral biopsy. It must be confirmed by positive JC virus RNA
      amplification in the cerebrospinal fluid. We report a case of progressive
      multifocal leucoencephalopathy occurring 18 months after liver transplantation
      for hepatitis C-related cirrhosis.

PMID- 16633318
TI  - [Massive intrahepatic haemorrhage responsible for an inferior vena cava syndrome:
      an exceptional complication of hepatocellular carcinoma].
AB  - Intralesional massive haemorrhage responsible for inferior vena cava syndrome is
      a very rare complication of hepatocellular carcinoma. A 36-year-old man with no
      past medical history was referred to hospital for abdominal pain with clinical
      and biological signs of internal bleeding. An abdominal CT scan showed a huge
      right liver mass, with regular margins and a fluid content, indicating a large
      intratumoral haemorrhage complicating hepatocellular carcinoma. Due to
      haemodynamic stability and the signs of inferior vena cava compression
      conservative management was chosen prior to surgical treatment of the tumour.
      Three months later, the huge liver mass remained unchanged but the inferior vena
      cava syndrome had decreased and the patient's condition improved. After
      evaluation of liver function and the extent of the tumour, a surgical procedure
      was performed via a subcostal incision with midline extension and sternotomy to
      control the intrapericardial inferior vena cava and perform a veno-venous bypass
      with the technique used for orthotopic liver transplantation. Then, right
      hepatectomy (segments V to VIII) was performed with an anterior approach. The
      postoperative course was uneventful. This two-step strategy allowed successful
      surgery for this rare complication of a hepatocellular carcinoma on a normal
      liver and could be recommended for the management of any unruptured intratumoral
      haemorrhages.

PMID- 16633319
TI  - Granulomatous hepatitis and hemophagocytic syndrome after bacillus Calmette
      Guerin bladder instillation.
AB  - Intravesical instillations of bacillus Calmette-Guerin are frequently used for
      treating superficial bladder carcinoma which is considered a safe treatment. We
      describe an unusual complication with hemophagocytosis and granulomatous
      hepatitis. Prompt diagnosis and treatment with corticosteroids, anti-tuberculous
      agents and intravenous immunoglobulins led to a rapid recovery.

PMID- 16633320
TI  - [Vascular malformation of the colon and lower gastrointestinal tract].

PMID- 16633321
TI  - [Germline tp53 neomutation in a patient with Li-Fraumeni syndrome and pancreatic
      adenocarcinoma].

PMID- 16633322
TI  - [Primary non hodgkin lymphoma of the anus and esophagus: a case report].

PMID- 16633323
TI  - [Duodenocaval fistula: a rare complication of a duodenal ulcer].

PMID- 16633324
TI  - [Impact of a recall campaign of the rules of the elimination of the injection
      equipment used for the treatment of hepatitis C in the centre region of France].

PMID- 16633325
TI  - Metabolic syndrome: current issues and perspectives.

PMID- 16633326
TI  - Insulin resistance: trigger or concomitant factor in the metabolic syndrome.
AB  - The metabolic syndrome (MS) is a cluster of metabolic abnormalities with insulin
      resistance as a major characteristic. The main adverse consequence of the MS is
      cardiovascular disease (CVD). Complex, mutually reinforcing interactions between
      obesity and insulin resistance largely account for the pathogenesis of MS.
      Central pathophysiologic features include: insulin resistance, atherogenic
      dyslipidemia, chiefly present as low HDL-C together with increases in
      triglycerides and small dense, low density lipoprotein particles, hypertension, a
      proinflammatory state, with increases in acute-phase reactants, and a
      prothrombotic state. Although lifestyle and overeating seem to be the triggering
      pathogenic factors, genetic elements are also involved in the pathogenesis of MS.
      When present, insulin resistance results in impaired insulin action in insulin
      sensitive tissues such as muscle, fat, and liver. Insulin resistance results in
      abnormalities of glucose metabolism, with reduced peripheral disposal of glucose
      in muscle and increased hepatic glucose output in the fasting state. But, most
      importantly, the progressively increasing concentration in circulating glucose
      leads to various abnormalities in insulin secretion. Elevated insulin levels
      themselves are atherogenic by inducing an oxidative stress and by stimulating
      sympathetic-nerve activity. Ectopic fat deposition, stress, proinflammatory
      state, and a maladaptive response of innate immunity may together concur to the
      development of the MS. When this condition is acknowledged, substantial
      modification of life style and correction of each single risk factor should be
      pursued without uncertainties and without hierarchical approach; this means that
      each risk factor should be treated and brought to target.

PMID- 16633327
TI  - The effect of estradiol metabolites and progestogens on the proliferation of
      human ovarian cancer cells.
AB  - The etiology of ovarian cancer appears to be associated with a long-term
      influence of estrogens. However, evidence is accumulating that certain estradiol
      metabolites may play a decisive role in the carcinogenesis of estrogen-dependent
      diseases. As yet little data are available on the association of estradiol
      metabolites and ovarian cancer. In vitro experiments revealed a potent
      stimulatory effect of certain metabolites on the proliferation of ovarian cancer
      cells, which is similar to or even stronger than the effect of their parent
      substance 17beta-estradiol. Therefore, the pattern of endogenous estradiol
      metabolism may play a role in defining ovarian cancer risk. This may be of
      importance in certain predisposed women who are treated with hormone therapy in
      the postmenopause. The role of progestogens in the genesis of ovarian cancer
      still remains unclear, rather a protective behaviour is suggested.
      Epidemiological studies indicate a possible increase in the risk for combined
      estrogen/progestin as compared to estrogen alone. It is ambigious whether a
      difference exists within the various progestogens. Apart from sex steroids growth
      factors play a crucial role in the genesis of ovarian cancer, although as yet
      little investigated. In vitro experiments indicate that progestogens do not have
      a protective role on the growth of pre-existing ovarian cancer cells, at least in
      the presence of growth factors. Further investigations are worthwile to evaluate
      possible differences between the effect of the various progestogens.

PMID- 16633328
TI  - Peptide hormones and lung cancer.
AB  - Several peptide hormones have been identified which alter the proliferation of
      lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer,
      produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and
      adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein
      coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC
      cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of
      nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have
      been developed for GRP, NT and AM receptors which function as cytostatic agents
      and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor
      antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung
      cancer cells. It remains to be determined if GRP, NT and AM receptors will served
      as molecular targets, for development of new therapies for the treatment of SCLC
      patients. Non-small cell lung cancer (NSCLC) cells also have a high density of
      GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients
      with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor.
      Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are
      not eligible for systemic chemotherapy. It is important to develop new
      therapeutic approaches using translational research techniques for the treatment
      of lung cancer patients.

PMID- 16633329
TI  - Sulfated oligosaccharides and tumor: promoter or inhibitor?
AB  - The topic about the role of sulfated oligosaccharides in carcinogenesis and
      progression of tumor remains controversial. The present review aims to evaluate
      the role of sulfated oligosaccharides in carcinogenesis and progression of tumor.
      The modification of sulfated oligosaccharides, especially chondroitin sulfate and
      heparan sulfate, is an important event in carcinogenesis and is correlated with
      the degree of differentiation. Enhance of chondroitin sulphate may promote
      carcinogenesis, while enhance of heparin sulphate may promote metastasis.
      Resistance of antiproliferation activity of sulfated oligosaccharides may
      contribute to the aberrant behavior of the cancer cell. Some researches supported
      that sulfated proteoglycan on the cell surface may enhance metastasis; while some
      soluble sulfated oligosaccharides could suppress metastasis. Thus, sulfated
      oligosaccharides play double roles, promoter or inhibitor, in carcinogenesis and
      tumor progression. Four topics about the correlation between sulfated
      oligosaccharides and carcinogensis and progression are very interesting and must
      be identified: whether the modified sulfated oligosaccharides have a different
      effect from the unmodified sulfated oligosaccharides; whether different sulfate
      oligosaccharides have the different action; whether the function of sulfated
      proteoglycan on the cell surface is different from that of soluble sulfated
      oligosaccharides; whether the function of sulfated oligosaccharides in primary
      tumor is different from that in metastasis tumor. Further data on the long-term
      safety of sulfate oligosaccharides for cancer patients are therefore required to
      allow overall risk-benefit assessments.

PMID- 16633330
TI  - Zollinger-Ellison syndrome in 2006: concepts from a clinical point of view.
AB  - Zollinger-Ellison syndrome (ZES) is characterised by peptic ulcers of the upper
      gastrointestinal tract failing to heal despite maximal medical therapy, diarrhoea
      and marked gastric acid hypersecretion associated with a gastrin-secreting tumour
      (gastrinoma). ZES might be associated with multiple endocrine neoplasia type 1.
      The main diagnostic features are hypergastrinemia and acid hypersecretion. When
      these parameters give borderline results, provocation test (with secretin or
      calcium) may be required. To identify the localisation of gastrinoma several
      imaging techniques have been proposed. Somatostatin receptor scintigraphy is
      capable to localise the tumour in 80% of the cases and to identify it even in
      anatomic sites other than pancreas and duodenum. Endoscopic ultrasonography has a
      sensitivity as high as 79-93% and a specificity of 93%. The 2 main principal
      therapeutic strategies are to control both the gastric acid hypersecretion and
      the growth of the neoplasia. Proton pump inhibitors (PPIs) are the drugs of
      choice for patients with ZES. Furthermore, safety of PPIs in the maintenance
      therapy has been proven both in short- and in long-term studies. The best
      surgical treatment is excision of gastrinoma before metastatic spread has
      occurred. Somatostatin-analogues can reduce both gastric acid hypersecretion and
      serum gastrin levels. Moreover, they have an antiproliferative effect.
      Chemotherapy, interferon and embolisation are indicated in rapidly evolving
      tumours or in cases in which the tumoral symptoms cannot be treated by other
      approaches.

PMID- 16633331
TI  - The metabolic syndrome and nonalcoholic fatty liver disease.
AB  - Accumulating evidence supports an association between nonalcoholic fatty liver
      disease (NAFLD) and metabolic syndrome, diabetes, and obesity. The epidemiology,
      pathogenesis, and approach to treatment of NAFLD follow the same trends as these
      other metabolic disorders, and insulin resistance is the key event linking NAFLD
      to these diseases. The impairment in fat and glucose metabolism that ensues once
      insulin resistance occurs leads to similar biochemical and clinical abnormalities
      in patients with NAFLD. Many recent studies investigating the cellular and
      genetic basis of these diseases have led to a better understanding of their
      pathogenesis and insight into treatment and management. The most effective
      treatment thus far is weight loss and the use of insulin-modulating pharmacologic
      agents. A few additional treatment strategies include the use of lipid-lowering,
      antioxidants or cytoprotective agents, but there is no single therapeutic
      approach that is effective for managing NAFLD. Future therapies may combine drugs
      that target specific pathways involved in NAFLD pathogenesis.

PMID- 16633332
TI  - Depression after a cerebrovascular accident. The importance of the integration of
      neurobiological and psychosocial pathogenic models.
AB  - Stroke survivors frequently suffer from depression. Research has focused on the
      incidence, phenomenology, course and risk factors of poststroke depression (PSD).
      Special attention has been paid to biological explanatory models, such as the
      lesion location and vascular depression hypotheses. In addition to such
      biological approaches, the role of psychosocial factors should not be neglected.
      This review critically discusses the proceedings in PSD research emphasizing the
      need for a biopsychosocial approach.

PMID- 16633333
TI  - Development and utilization of a quantitative polymerase chain reaction assay to
      evaluate human polyomavirus JC DNA load.
AB  - AIM: Quantitative polymerase chain reaction (PCR) analysis to evaluate virus load
      in comparison with the patient's base-line virus levels would be an optimal
      diagnostic approach to monitoring human polyomavirus infections and to
      investigate their possible involvement in the onset of nephropathy in this
      patient group. Studies on the correlation between viral burden and renal disease
      have pointed to the incidence of JC virus (JCV) related progressive multifocal
      leukoencephalopathy (PML) occurring in renal and haematopoietic stem cell
      transplant recipients. METHODS: We developed a reliable internally-controlled
      quantitative PCR assay to measure JCV-DNA in fluid samples of urine, serum and
      cerebrospinal fluid (CSF) by densitometric analysis of the amplification
      products. The assay was also used to evaluate the JCV load in CFS samples from
      patients with suspected demyelinating syndrome and in urine and serum samples
      from healthy subjects and renal transplant recipients. RESULTS: All CSF samples
      from the 51 patients with suspected demyelinating syndrome tested JCV-DNA
      negative: none of them had a diagnosed PML. Analysis of the prevalence of JCV
      viruria and JCV-viraemia confirmed our previous data. JCV-viruria was detected in
      17% of renal transplant recipients and 26.6% of healthy controls; JCV-viraemia
      was found in 3.4% of transplant patients and 0% in controls. Noteworthy was a
      lower prevalence of JCV-viraemia in the 116 (3.4%) renal transplant patients than
      the prevalence previously reported for the 51 (11.8%) patients with suspected
      demyelinating syndrome. The mean viral load of viruria was much higher in the
      healthy controls than in the transplant recipients [104020 DNA copies/mL (DS+/
      62284) vs 4136 DNA copies/mL (DS+/-77371)]. CONCLUSIONS: The quantitative PCR
      assay developed in our lab offers in 2 h time a reliable true quantification of
      viral DNA by densitometric analysis of the amplification product. To check for
      the possible presence of potential Taq polymerase inhibitors an internal control
      (the homemade pJCV-C plasmid) is used. The relation between polyomavirus
      infections and their possible involvement in post-transplant pathologies need
      further investigation. It would be useful to monitor the JCV-DNA load in urine
      and serum from more renal transplant recipients, including patients with
      nephropathy or active graft rejection over a longer period of time.

PMID- 16633334
TI  - Predictors of impaired blood pressure homeostasis during acute and sustained
      orthostasis in patients with type 2 diabetes.
AB  - AIM: Sympathetic failure with acute postural hypotension is a common feature of
      advanced autonomic neuropathy in type 2 diabetes. It is unknown, however,
      whether: a) the presence of sympathetic autonomic neuropathy is also a powerful
      predictor of postural blood pressure changes during sustained orthostasis and b)
      other factors affecting baroreceptor and neuro-hormonal control might play a
      role. METHODS: Systolic blood pressure (SBP) was measured during supine rest and
      after 2, 5, and 20 min of active orthostasis in 45 males with type 2 diabetes
      (age 56.4+/-8.2 years, mean+/-SD) and different degrees of autonomic neuropathy
      (absence of neuropathy, n=26, parasympathetic neuropathy, n=9, and sympathetic
      neuropathy, n=10). Eight healthy subjects (50.1+/-11.6 years) served as controls.
      A multiple backward regression analysis was performed to identify independent
      predictors of SBP changes during orthostasis. The regression model included
      presence/absence of sympathetic autonomic neuropathy, age, diabetes duration,
      presence/absence of hypertension, baseline SBP and neuro-hormonal parameters
      (plasma adrenaline, noradrenaline, plasma renin activity, and aldosterone).
      RESULTS: Sympathetic autonomic neuropathy (P=0.005), baseline SBP (P=0.001), and
      adrenaline (P=0.003) independently predicted SBP changes after 2 min (R2=0.64);
      sympathetic autonomic neuropathy (P<0.001), baseline adrenaline (P=0.008), and
      plasma renin activity (P=0.006) predicted SBP changes after 5 min (R2=0.58);
      whereas sympathetic autonomic neuropathy (P<0.001) and baseline SBP (P<0.001)
      predicted SBP changes after 20 min orthostasis (R2=0.65). CONCLUSIONS: The
      presence of sympathetic autonomic neuropathy and higher supine SBP values remain
      strong and independent predictors of SBP fall not only during the acute
      transition from supine to standing position but also during sustained orthostasis
      in type 2 diabetes. Lower baseline plasma adrenaline concentrations and plasma
      renin activity are also involved, though to a lesser extent, in the genesis of
      this haemodynamic response.

PMID- 16633335
TI  - At the heart of the chromosome: SMC proteins in action.
AB  - Structural maintenance of chromosomes (SMC) proteins are ubiquitous in organisms
      from bacteria to humans, and function as core components of the condensin and
      cohesin complexes in eukaryotes. SMC proteins adopt a V-shaped structure with two
      long arms, each of which has an ATP-binding head domain at the distal end. It is
      important to understand how these uniquely designed protein machines interact
      with DNA strands and how such interactions are modulated by the ATP-binding and 
      hydrolysis cycle. An emerging idea is that SMC proteins use a diverse array of
      intramolecular and intermolecular protein-protein interactions to actively fold,
      tether and manipulate DNA strands.

PMID- 16633336
TI  - Regulation of DNA repair by ubiquitylation.
AB  - The process of ubiquitylation is best known for its role in targeting proteins
      for degradation by the proteasome. However, recent studies of DNA-repair and DNA
      damage-response pathways have significantly broadened the scope of the role of
      ubiquitylation to include non-proteolytic functions of ubiquitin. These pathways
      involve the monoubiquitylation of key DNA-repair proteins that have regulatory
      functions in homologous recombination and translesion DNA synthesis, and involve
      the polyubiquitylation of nucleotide-excision-repair proteins.

PMID- 16633337
TI  - ARF proteins: roles in membrane traffic and beyond.
AB  - The ADP-ribosylation factor (ARF) small GTPases regulate vesicular traffic and
      organelle structure by recruiting coat proteins, regulating phospholipid
      metabolism and modulating the structure of actin at membrane surfaces. Recent
      advances in our understanding of the signalling pathways that are regulated by
      ARF1 and ARF6, two of the best characterized ARF proteins, provide a molecular
      context for ARF protein function in fundamental biological processes, such as
      secretion, endocytosis, phagocytosis, cytokinesis, cell adhesion and tumour-cell
      invasion.

PMID- 16633338
TI  - VEGF receptor signalling - in control of vascular function.
AB  - Vascular endothelial growth-factor receptors (VEGFRs) regulate the cardiovascular
      system. VEGFR1 is required for the recruitment of haematopoietic precursors and
      migration of monocytes and macrophages, whereas VEGFR2 and VEGFR3 are essential
      for the functions of vascular endothelial and lymphendothelial cells,
      respectively. Recent insights have shed light onto VEGFR signal transduction and
      the interplay between different VEGFRs and VEGF co-receptors in development,
      adult physiology and disease.

PMID- 16633339
TI  - A TAS1R receptor-based explanation of sweet 'water-taste'.
AB  - 'Water-tastes' are gustatory after-impressions elicited by water following the
      removal of a chemical solution from the mouth, akin to colour after-images
      appearing on 'white' paper after fixation on coloured images. Unlike colour after
      images, gustatory after-effects are poorly understood. One theory posits that
      'water-tastes' are adaptation phenomena, in which adaptation to one taste
      solution causes the water presented subsequently to act as a taste stimulus. An
      alternative hypothesis is that removal of the stimulus upon rinsing generates a
      receptor-based, positive, off-response in taste-receptor cells, ultimately
      inducing a gustatory perception. Here we show that a sweet 'water-taste' is
      elicited when sweet-taste inhibitors are rinsed away. Responses of cultured cells
      expressing the human sweetener receptor directly parallel the psychophysical
      responses-water rinses remove the inhibitor from the heteromeric sweetener
      receptor TAS1R2-TAS1R3, which activates cells and results in the perception of
      strong sweetness from pure water. This 'rebound' activity occurs when equilibrium
      forces on the two-state allosteric sweet receptors result in their coordinated
      shift to the activated state upon being released from inhibition by rinsing.

PMID- 16633340
TI  - PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia
      prevention.
AB  - Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and
      activation that fulfils immediate demands for haematopoiesis without compromising
      long-term stem cell maintenance, yet little is known about the molecular events
      governing this balance. Phosphatase and tensin homologue (PTEN) functions as a
      negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway,
      which has crucial roles in cell proliferation, survival, differentiation and
      migration. Here we show that inactivation of PTEN in bone marrow HSCs causes
      their short-term expansion, but long-term decline, primarily owing to an enhanced
      level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice,
      but have an impaired ability to sustain haematopoietic reconstitution, reflecting
      the dysregulation of their cell cycle and decreased retention in the bone marrow
      niche. Mice with PTEN-mutant bone marrow also have an increased representation of
      myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD).
      Notably, the cell populations that expand in PTEN mutants match those that become
      dominant in the acute myeloid/lymphoid leukaemia that develops in the later
      stages of MPD. Thus, PTEN has essential roles in restricting the activation of
      HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.

PMID- 16633341
TI  - Neurons in the orbitofrontal cortex encode economic value.
AB  - Economic choice is the behaviour observed when individuals select one among many
      available options. There is no intrinsically 'correct' answer: economic choice
      depends on subjective preferences. This behaviour is traditionally the object of
      economic analysis and is also of primary interest in psychology. However, the
      underlying mental processes and neuronal mechanisms are not well understood.
      Theories of human and animal choice have a cornerstone in the concept of 'value'.
      Consider, for example, a monkey offered one raisin versus one piece of apple:
      behavioural evidence suggests that the animal chooses by assigning values to the
      two options. But where and how values are represented in the brain is unclear.
      Here we show that, during economic choice, neurons in the orbitofrontal cortex
      (OFC) encode the value of offered and chosen goods. Notably, OFC neurons encode
      value independently of visuospatial factors and motor responses. If a monkey
      chooses between A and B, neurons in the OFC encode the value of the two goods
      independently of whether A is presented on the right and B on the left, or vice
      versa. This trait distinguishes the OFC from other brain areas in which value
      modulates activity related to sensory or motor processes. Our results have broad
      implications for possible psychological models, suggesting that economic choice
      is essentially choice between goods rather than choice between actions. In this
      framework, neurons in the OFC seem to be a good candidate network for value
      assignment underlying economic choice.

PMID- 16633342
TI  - End stopping in V1 is sensitive to contrast.
AB  - Common situations that result in different perceptions of grouping and border
      ownership, such as shadows and occlusion, have distinct sign-of-contrast
      relationships at their edge-crossing junctions. Here we report a property of end
      stopping in V1 that distinguishes among different sign-of-contrast situations,
      thereby obviating the need for explicit junction detectors. We show that the
      inhibitory effect of the end zones in end-stopped cells is highly selective for
      the relative sign of contrast between the central activating stimulus and stimuli
      presented at the end zones. Conversely, the facilitatory effect of end zones in
      length-summing cells is not selective for the relative sign of contrast between
      the central activating stimulus and stimuli presented at the end zones. This
      finding indicates that end stopping belongs in the category of cortical
      computations that are selective for sign of contrast, such as direction
      selectivity and disparity selectivity, but length summation does not.

PMID- 16633343
TI  - Gene expression changes and molecular pathways mediating activity-dependent
      plasticity in visual cortex.
AB  - Two key models for examining activity-dependent development of primary visual
      cortex (V1) involve either reduction of activity in both eyes via dark-rearing
      (DR) or imbalance of activity between the two eyes via monocular deprivation
      (MD). Combining DNA microarray analysis with computational approaches, RT-PCR,
      immunohistochemistry and physiological imaging, we find that DR leads to (i)
      upregulation of genes subserving synaptic transmission and electrical activity,
      consistent with a coordinated response of cortical neurons to reduction of visual
      drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin
      expressing interneurons as underlying the delay in cortical maturation after DR.
      MD partially activates homeostatic mechanisms but differentially upregulates
      molecular pathways related to growth factors and neuronal degeneration,
      consistent with reorganization of connections after MD. Expression of a binding
      protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD,
      and exogenous application of IGF1 prevents the physiological effects of MD on
      ocular dominance plasticity examined in vivo.

PMID- 16633344
TI  - BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine
      withdrawal.
AB  - The neural mechanism underlying the relapse to drug use after drug withdrawal is
      largely unknown. We found that after withdrawal from repeated cocaine exposure,
      excitatory synapses onto dopamine neurons in the ventral tegmental area (VTA) of
      the rat midbrain became highly susceptible to potentiation by weak presynaptic
      stimuli, an effect requiring endogenous brain-derived neurotrophic factor
      tyrosine kinase B (BDNF-TrkB) signaling. The elevated BDNF expression in the VTA
      after cocaine withdrawal may prime these synapses for potentiation by cue
      associated activity, triggering drug craving and relapse.

PMID- 16633345
TI  - ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune
      responses.
AB  - The TPL-2 MEK kinase is essential for activation of the Erk MAP kinase pathway
      during innate immune responses. TPL-2 is found in complex with ABIN-2 (A20
      binding inhibitor of NF-kappaB 2). Here, using antigen-presenting cells from ABIN
      2-deficient mice, we show that ABIN-2 was required for optimal activation of Erk
      induced by receptors that signal via TPL-2, including Toll-like receptor 4 and
      tumor necrosis factor receptor 1 in macrophages, and CD40 in B cells. ABIN-2 was
      necessary for the maintenance of TPL-2 protein stability. In contrast, ABIN-2
      deficiency did not affect agonist-induced regulation of transcription factor NF
      kappaB. Stimulation of ABIN-2-deficient macrophages via Toll-like receptor 4
      showed that different thresholds of Erk signaling were required for optimal
      induction of tumor necrosis factor and interleukin 1beta. Thus, ABIN-2 acts to
      positively regulate the Erk signaling potential by stabilizing TPL-2.

PMID- 16633346
TI  - Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to
      vascularized grafts.
AB  - The induction of alloantigen-specific unresponsiveness remains an elusive goal in
      organ transplantation. Here we identify plasmacytoid dendritic cells (pDCs) as
      phagocytic antigen-presenting cells essential for tolerance to vascularized
      cardiac allografts. Tolerizing pDCs acquired alloantigen in the allograft and
      then moved through the blood to home to peripheral lymph nodes. In the lymph
      node, alloantigen-presenting pDCs induced the generation of CCR4+ CD4+ CD25+
      Foxp3+ regulatory T cells (Treg cells). Depletion of pDCs or prevention of pDC
      lymph node homing inhibited peripheral Treg cell development and tolerance
      induction, whereas adoptive transfer of tolerized pDCs induced Treg cell
      development and prolonged graft survival. Thus, alloantigen-presenting pDCs home
      to the lymph nodes in tolerogenic conditions, where they mediate alloantigen
      specific Treg cell development and allograft tolerance.

PMID- 16633347
TI  - Neuron-mediated generation of regulatory T cells from encephalitogenic T cells
      suppresses EAE.
AB  - Neurons have been neglected as cells with a major immune-regulatory function
      because they do not express major histocompatibility complex class II. Our data
      show that neurons are highly immune regulatory, having a crucial role in
      governing T-cell response and central nervous system (CNS) inflammation. Neurons
      induce the proliferation of activated CD4+ T cells through B7-CD28 and
      transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways,
      resulting in amplification of T-cell receptor signaling through phosphorylated
      ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells
      results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+
      FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and
      inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on
      cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of
      TGF-beta1, however, is important for the proliferative arrest of Treg cells.
      Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of
      Treg cells. These findings show that generation of neuron-dependent Treg cells in
      the CNS is instrumental in regulating CNS inflammation.

PMID- 16633348
TI  - Endogenous microRNA regulation suppresses transgene expression in hematopoietic
      lineages and enables stable gene transfer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by
      repressing translation of target cellular transcripts. Increasing evidence
      indicates that miRNAs have distinct expression profiles and play crucial roles in
      numerous cellular processes, although the extent of miRNA regulation is not well
      known. By challenging mice with lentiviral vectors encoding target sequences of
      endogenous miRNAs, we show the efficiency of miRNAs in sharply segregating gene
      expression among different tissues. Transgene expression from vectors
      incorporating target sequences for mir-142-3p was effectively suppressed in
      intravascular and extravascular hematopoietic lineages, whereas expression was
      maintained in nonhematopoietic cells. This expression profile, which could not be
      attained until now, enabled stable gene transfer in immunocompetent mice, thus
      overcoming a major hurdle to successful gene therapy. Our results provide novel
      in situ evidence of miRNA regulation and demonstrate a new paradigm in vector
      design with applications for genetic engineering and therapeutic gene transfer.

PMID- 16633349
TI  - Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular
      basis of an antimicrobial in vitro-in vivo paradox.
AB  - Discrepancies between resistance in vitro and therapeutic efficacy in vivo are
      generally attributed to failure of laboratory susceptibility tests to reflect an
      antibiotic's pharmacokinetic or pharmacodynamic properties. We show here that
      this phenomenon can result from differential in vitro-in vivo expression of
      bacterial determinants of antibiotic susceptibility. We found that an in vivo
      induced virulence factor, Hpt, also mediates uptake of fosfomycin in Listeria
      monocytogenes. These bacteria therefore seem resistant to fosfomycin in vitro,
      although they are in fact susceptible to the antibiotic during infection.

PMID- 16633350
TI  - Statistical pattern matching facilitates the design of polyvalent inhibitors of
      anthrax and cholera toxins.
AB  - Numerous biological processes involve the recognition of a specific pattern of
      binding sites on a target protein or surface. Although ligands displayed by
      disordered scaffolds form stochastic rather than specific patterns, theoretical
      models predict that recognition will occur between patterns that are
      characterized by similar or "matched" statistics. Endowing synthetic biomimetic
      structures with statistical pattern matching capabilities may improve the
      specificity of sensors and resolution of separation processes. We demonstrate
      that statistical pattern matching enhances the potency of polyvalent
      therapeutics. We functionalized liposomes with an inhibitory peptide at different
      densities and observed a transition in potency at an interpeptide separation that
      matches the distance between ligand-binding sites on the heptameric component of
      anthrax toxin. Pattern-matched polyvalent liposomes inhibited anthrax toxin in
      vitro at concentrations four orders of magnitude lower than the corresponding
      monovalent peptide, and neutralized this toxin in vivo. Statistical pattern
      matching also enhanced the potency of polyvalent inhibitors of cholera toxin.
      This facile strategy should be broadly applicable to the detection and
      neutralization of toxins and pathogens.

PMID- 16633351
TI  - Site-specific PEGylation of native disulfide bonds in therapeutic proteins.
AB  - Native disulfide bonds in therapeutic proteins are crucial for tertiary structure
      and biological activity and are therefore considered unsuitable for chemical
      modification. We show that native disulfides in human interferon alpha-2b and in
      a fragment of an antibody to CD4(+) can be modified by site-specific
      bisalkylation of the two cysteine sulfur atoms to form a three-carbon PEGylated
      bridge. The yield of PEGylated protein is high, and tertiary structure and
      biological activity are retained.

PMID- 16633352
TI  - Macrophage-stimulating protein differently affects human alveolar macrophages
      from smoker and non-smoker patients: evaluation of respiratory burst, cytokine
      release and NF-kappaB pathway.
AB  - Macrophage activation is a key feature of inflammatory reactions occurring during
      bacterial infections, immune responses and tissue injury. We previously
      demonstrated that human macrophages of different origin express the tyrosine
      kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON)
      and produce superoxide anion (O(2)(-)) when challenged with macrophage
      stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to
      evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy
      volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic
      pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory
      burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation. MSP
      effects were compared with those induced by known AM stimuli, for example,
      phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine,
      lipopolysaccharide.MSP evokes O(2)(-) production, cytokine release and NF-kappaB
      activation in a concentration-dependent manner. By evaluating the respiratory
      burst, we demonstrate a significantly increased O(2)(-) production in AM from
      healthy smokers or smokers with pulmonary fibrosis, as compared to non-smokers,
      thus suggesting MSP as an enhancer of cigarette smoke toxicity. Besides inducing
      interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers
      an enhanced tumor necrosis factor-alpha release, especially in healthy and
      pulmonary fibrosis smokers. On the contrary, MSP-induced IL-10 release is higher
      in AM from healthy non-smokers. MSP activates the transcription factor NF-kappaB;
      this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in
      p50 subunit translocation). This effect is receptor-mediated, as it is prevented
      by a monoclonal anti-human MSP antibody. The higher effectiveness of MSP in AM
      from healthy smokers and patients with pulmonary fibrosis is suggestive of its
      role in these clinical conditions.

PMID- 16633353
TI  - Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the
      antipsychotic drug clozapine.
AB  - Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which
      may lead to torsades de pointes and sudden death. To investigate the
      arrhythmogenic side effects of clozapine, we studied the impact of clozapine on
      human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and
      HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig
      cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the
      currents at the end of voltage steps, and the tail currents of HERG. The IC(50)
      for the clozapine blockade of HERG currents in Xenopus oocytes progressively
      decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV
      and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade
      of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The
      clozapine-induced blockade of HERG currents was time dependent: the fractional
      current was 0.903 of the control at the beginning of the pulse, but declined to
      0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of
      HERG currents was use-dependent, exhibiting more rapid onset and greater steady
      state blockade at higher frequencies of activation, with a partial relief of
      blockade observed when the frequency of activation was decreased. In guinea-pig
      ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM
      clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr))
      by 24.7 and 79.6%, respectively, but did not significantly block the slowly
      activating delayed rectifier K(+) current (I(Ks)). Our findings collectively
      suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute
      to the arrhythmogenic side effects of clozapine.

PMID- 16633354
TI  - Inhibition of stimulated meningeal blood flow by a calcitonin gene-related
      peptide binding mirror-image RNA oligonucleotide.
AB  - Calcitonin gene-related peptide (CGRP) released from trigeminal afferents is
      known to play an important role in the control of intracranial blood flow. In a
      rat preparation with exposed cranial dura mater, periods of electrical
      stimulation induce increases in meningeal blood flow. These responses are due to
      arterial vasodilatation mediated in part by the release of CGRP. In this
      preparation, the effect of a CGRP-binding mirror-image oligonucleotide
      (Spiegelmer NOX-C89) was examined. Spiegelmer NOX-C89 applied topically at
      concentrations between 10(-7) and 10(-5) M to the exposed dura mater led to a
      dose-dependent inhibition of the electrically evoked blood flow increases. The
      highest dose reduced the mean increases in flow to 56% of the respective control
      levels. A nonfunctional control Spiegelmer (not binding to CGRP) was ineffective
      in changing blood flow increases. Intravenous injection of NOX-C89 (5 mg kg(-1))
      reduced the evoked blood flow increases to an average of 65.5% of the control.
      The basal blood flow was not changed by any of the applied substances. In
      addition, an ex vivo preparation of the hemisected rat skull was used to
      determine CGRP release from the cranial dura mater caused by antidromic
      activation of meningeal afferents. In this model, 10(-6) M of NOX-C89 reduced the
      evoked CGRP release by about 50%. We conclude that increases in meningeal blood
      flow due to afferent activation can be reduced by sequestering the released CGRP
      and thus preventing it from activating vascular CGRP receptors. Moreover, the
      Spiegelmer NOX-C89 may inhibit CGRP release from meningeal afferents. Therefore,
      the approach to interfere with the CGRP/CGRP receptor system by binding the CGRP
      may open a new opportunity for the therapy of diseases that are linked to
      excessive CGRP release such as some forms of primary headaches.

PMID- 16633355
TI  - Effect of Boswellia serrata on intestinal motility in rodents: inhibition of
      diarrhoea without constipation.
AB  - Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be
      effective in reducing diarrhoea in patients with inflammatory bowel disease. In
      the present study, we evaluated the effect of a Boswellia serrata gum resin
      extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed
      electrically-, acetylcholine-, and barium chloride-induced contractions in the
      isolated guinea-pig ileum, being more potent in inhibiting the contractions
      induced by acetylcholine and barium chloride. The inhibitory effect of BSE on
      acetylcholine-induced contractions was reduced by the L-type Ca(2+) channel
      blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum Ca(2+)
      ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV inhibitor
      rolipram or by the lipoxygenase inhibitor zileuton. 3-acetyl-11-keto-beta
      boswellic acid, one of the main active ingredients of B. serrata, inhibited
      acetylcholine-induced contractions. BSE inhibited upper gastrointestinal transit
      in croton oil-treated mice as well as castor oil-induced diarrhoea. However, BSE
      did not affect intestinal motility in control mice, both in the small and in the
      large intestine. It is concluded that BSE directly inhibits intestinal motility
      with a mechanism involving L-type Ca(2+) channels. BSE prevents diarrhoea and
      normalizes intestinal motility in pathophysiological states without slowing the
      rate of transit in control animals. These results could explain, at least in
      part, the clinical efficacy of this Ayurvedic remedy in reducing diarrhoea in
      patients with inflammatory bowel disease.

PMID- 16633356
TI  - Enzymatic pathways involved in the generation of endothelin-1(1-31) from
      exogenous big endothelin-1 in the rabbit aorta.
AB  - We investigated whether blood vessels contribute to the production of ET-1(1-31)
      from exogenous big endothelin-1 (BigET-1) in the rabbit and assessed which
      enzymes are involved in this process. Vascular reactivity experiments, using
      standard muscle bath procedures, showed that BigET-1 induces contraction in
      endothelium-intact rabbit aortic rings. Preincubation of the rings with
      phosphoramidon, CGS35066 or thiorphan reduced BigET-1-induced contraction.
      Conversely, chymostatin did not affect BigET-1-induced contraction. Thiorphan and
      phosphoramidon, but not CGS35066 or chymostatin, reduced ET-1(1-31)-induced
      contraction. None of the enzymatic inhibitors affected the contraction afforded
      by ET-1.BQ123-, but not BQ788-, selective antagonists for ET(A) and ET(B)
      receptors, respectively, produced concentration-dependent rightward displacements
      of the ET-1(1-31) and ET-1 concentration-response curves. By the use of enzymatic
      assays, we found that the aorta, as well as the heart, lung, kidney and liver,
      possess a chymase-like activity. Enzyme immunoassays detected significant levels
      of Ir-ET-1(1-31) in bathing medium of aortas after the addition of BigET-1 (30
      nM). Neither thiorphan nor chymostatin altered the levels of Ir-ET-1(1-31).
      Conversely, the levels of Ir-ET-1(1-31) were increased in the presence of
      phosphoramidon. This marked increase of the 31-amino-acid peptide was abolished
      when phosphoramidon and chymostatin were added simultaneously. The major new
      finding of the present work is that the rabbit aorta generates ET-1(1-31) from
      exogenously administered BigET-1. Additionally, by measuring the production of ET
      1(1-31), we showed that a chymase-like enzyme is involved in this process when
      ECE and NEP are inhibited by phosphoramidon. Our results also suggest that ET-1(1
      31) is an alternate intermediate in the production of ET-1 following BigET-1
      administration. Finally, we showed that NEP is the predominant enzymatic pathway
      involved in the cleavage of ET-1(1-31) to a bioactive metabolite that will act on
      ET(A) receptors to induce contraction in the rabbit aorta.

PMID- 16633357
TI  - Recombinant P-selectin glycoprotein-ligand-1 delays thrombin-induced platelet
      aggregation: a new role for P-selectin in early aggregation.
AB  - 1. P-selectin is involved, with P-selectin glycoprotein (GP)-ligand-1 (PSGL-1),
      in platelet/leukocyte interactions during thrombo-inflammatory reactions; it also
      stabilizes platelet aggregates. Its antagonism accelerates thrombolysis and
      enhances the anti-aggregatory effects of GPIIb-IIIa inhibitors. This study was
      designed to investigate the mechanisms of P-selectin-mediated platelet
      aggregation. 2. In freshly isolated human platelets, P-selectin translocation
      after thrombin stimulation increased rapidly to 48, 72, and 86% positive
      platelets after 60, 120, and 300 s, respectively. Platelet aggregation at 60 s
      post-stimulation averaged 46.7 +/- 1.9% and its extent followed closely the
      kinetics of P-selectin translocation. 3. Pre-treatment of platelets with P
      selectin antagonists, a recombinant PSGL-1 (rPSGL-Ig) or a blocking monoclonal
      antibody, significantly delayed platelet aggregation in a dose-dependent manner.
      At 100 microg ml(-1) of rPSGL-Ig, platelet aggregation was completely inhibited
      up to 60 s post-stimulation and increased thereafter to reach maximal aggregation
      at 5 min. The second phase of platelet aggregation, in the presence of rPSGL-Ig,
      was completely prevented by the addition of a GPIIb-IIIa antagonist (Reopro) at
      60 s, whereas its addition in the absence of rPSGL-Ig was without any significant
      effect. 4. Combination of rPSGL-Ig with Reopro or with an inhibitor of Pi3K
      (LY294002), which reduces GPIIb-IIIa activation, showed to be more effective in
      inhibiting platelet aggregation, in comparison to the effects observed
      individually. 5. rPSGL-Ig blocks P-selectin, whereas Reopro and LY294002 block
      GPIIb-IIIa and its activation, respectively, without a major effect on the
      percentage of platelets expressing P-selectin. 6. In summary, platelet P-selectin
      participates with GPIIb-IIIa in the initiation of platelet aggregation. Its
      inhibition, with rPSGL-Ig, delays the aggregation process and increases the anti
      aggregatory potency of Reopro. Thus, combination of P-selectin and GPIIb-IIIa
      antagonism may constitute a promising therapeutic option in the management of
      thrombotic disorders.

PMID- 16633358
TI  - Impaired phagocytic mechanism in annexin 1 null macrophages.
AB  - The role of the anti-inflammatory protein annexin-A1 (Anx-A1) in the phagocytic
      process has been investigated using a murine bone marrow culture-derived
      macrophage model from Anx-A1(+/+) and Anx-A1(-/-) mice. Macrophages prepared from
      Anx-A1(-/-) mice exhibited a reduced ingestion of zymosan, Neisseria meningitidis
      or sheep red blood cells, when compared to Anx-A1(+/+) cells and in the case of
      zymosan this effect was also mirrored by a reduced clearance in vivo when
      particles were injected into the peritoneal cavity of Anx-A1(-/-) mice. The
      ablation of the Anx-A1 gene did not cause any apparent cytoskeletal defects
      associated with particle ingestion but the cell surface expression of the key
      adhesion molecule CD11b was depressed in the Anx-A1(-/-) cells providing a
      possible explanation for the attenuated phagocytic potential of these cells. The
      production of the cytokines TNFalpha and IL-6 was increased in Anx-A1(-/-)
      macrophages following phagocytosis of all types of particle.

PMID- 16633359
TI  - A prospective, randomized study of cryotherapy during administration of high-dose
      melphalan to decrease the severity and duration of oral mucositis in patients
      with multiple myeloma undergoing autologous peripheral blood stem cell
      transplantation.
AB  - Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2)
      followed by autologous stem cell transplantation were randomly assigned to
      receive oral cryotherapy or room temperature normal saline rinses 30 min before
      and for 6 h after high-dose therapy. Patients were evaluated for the development
      of mucositis using the National Cancer Institute grading system as well as
      evaluation of secondary measures such as days of total parenteral nutrition
      (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric
      intake for 28 days after transplant. Patients self-scored their pain, swallowing,
      drinking, eating, sleeping and taste alterations for 28 days. The primary end
      point of this trial was the incidence of grades 3-4 mucositis. Compared to the
      normal saline group, patients using cryotherapy experienced less grade 3-4
      mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had
      statistically lower uses of narcotics and TPN, although there were no differences
      in length of hospitalization or weight loss. Patient-reported pain was
      significantly lower and activities were significantly better in the cryotherapy
      group.

PMID- 16633360
TI  - Allogeneic bone marrow transplantation (BMT) for refractory Behcet's disease with
      severe CNS involvement.

PMID- 16633361
TI  - Autologous hematopoietic stem cell transplantation for older patients with
      relapsed non-Hodgkin's lymphoma.
AB  - To evaluate autologous stem cell transplant (ASCT) in older patients with
      intermediate grade non-Hodgkin's lymphoma (NHL), the Mayo Clinic Rochester BMT
      database was reviewed for all patients 60 years of age and older who received
      ASCT for NHL between September 1995 and February 2003. Factors evaluated included
      treatment-related mortality (TRM), event-free survival (EFS) and overall survival
      (OS). Ninety-three patients were identified, including twenty-four (26%) over the
      age of 70 years. Treatment-related mortality (5.4%) was not significantly
      different when compared to a younger cohort (2.2%). At a median follow-up of 14
      months (0.6-87.6 months), the estimated median survival is 25 months (95%
      confidence interval (CI) 12-38) in the older group compared to 56 months (95% CI
      37-75) (P=0.037) in the younger group. The estimated 4-year EFS was 38% for the
      older group compared to 42% in the younger cohort (P=0.1). By multivariate
      analysis, the only factor found to influence survival in the older group was age
      adjusted International Prognostic Index at relapse, 0-1 better than 2-3 (P=0.03).
      Autologous stem-cell transplant can be safely performed in patients 60 years or
      older with chemotherapy sensitive relapsed or first partial remission NHL. The
      outcome may not be different from that of younger patients in terms of TRM and
      EFS.

PMID- 16633362
TI  - Autologous stem cell transplant in ALL: who should we be transplanting in first
      remission?
AB  - Long-term disease-free survival (DFS) has been reported after autologous stem
      cell transplantation for acute lymphoblastic leukemia. Phase II studies have
      evaluated its role in first and subsequent complete remission (CR) with DFS rates
      of up to 50%. It has been under-utilized in 1st CR in part, due to a concern that
      patients who relapse after autologous stem cell transplantation (ASCT) have fewer
      options for salvage treatment of relapsed disease. Unfortunately, survival rates
      of <5% are reported in patients who relapse, regardless of initial therapy. Few
      prospective, randomized trials have analyzed large enough numbers of patients to
      allow us to determine the appropriate patient population for autologous
      transplantation. Although variability in the available studies makes it difficult
      to draw a definite conclusion, and many issues remain unresolved, available data
      suggests that there may be a group of patients for whom ASCT in first remission
      is a reasonable and perhaps superior treatment choice. Factors such as risk
      features at diagnosis, and minimal residual disease following induction therapy
      greatly affect outcome following ASCT. The available data as well as the
      questions that remain to be answered will be discussed and reviewed.

PMID- 16633363
TI  - A randomized phase III comparative trial of immediate consolidation with high
      dose chemotherapy and autologous peripheral blood progenitor cell support
      compared to observation with delayed consolidation in women with metastatic
      breast cancer and only bone metastases following intensive induction
      chemotherapy.
AB  - The prognosis for patients with metastatic breast cancer remains poor. Metastatic
      breast cancer confined to the bones may have a better prognosis, especially
      hormone receptor-positive disease. We performed a prospective, randomized
      clinical trial to compare immediate consolidation with high-dose chemotherapy and
      hematopoietic support versus observation with high-dose consolidation at the time
      of disease progression in women with metastatic breast cancer and only bone
      metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil
      and methotrexate before randomization. In all, 85 patients were enrolled and 69
      were randomized. The median follow-up is 8.1 years from randomization. The median
      event-free survival (EFS) for the immediate transplant arm is 12 months and for
      the observation arm is 4.3 months (P<0.0001). The median overall survival for the
      immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a
      difference that is not statistically significant. Immediate high-dose
      chemotherapy and radiation therapy as consolidation offers a clinically and
      statistically significant improvement in EFS compared with radiation therapy
      alone following induction chemotherapy for women with metastatic breast cancer
      confined to the bones.

PMID- 16633364
TI  - Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis.
AB  - Endometrial cancer is the most common gynaecological cancer, and is associated
      with endometrial hyperplasia, unopposed oestrogen exposure and adjuvant therapy
      for breast cancer using selective oestrogen-receptor modulators (SERMs),
      particularly tamoxifen. Oestrogen and SERMs are thought to be involved in
      endometrial carcinogenesis through their effects on transcriptional regulation.
      Ultimately, oestrogen and SERMs affect the transduction of cellular signalling
      pathways that govern cell growth and proliferation, through downstream effectors
      such as PAX2 (paired box 2).

PMID- 16633365
TI  - Ubiquitin ligases: cell-cycle control and cancer.
AB  - A driving force of the cell cycle is the activation of cyclin-dependent kinases
      (CDKs), the activities of which are controlled by the ubiquitin-mediated
      proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin
      ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting
      complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of
      many of these regulators. Deregulation of the proteolytic system might result in
      uncontrolled proliferation, genomic instability and cancer. Cumulative clinical
      evidence shows alterations in the ubiquitylation of cell-cycle regulators in the
      aetiology of many human malignancies. A better understanding of the
      ubiquitylation machinery will provide new insights into the regulatory biology of
      cell-cycle transitions and the development of anti-cancer drugs.

PMID- 16633366
TI  - Is there more to BARD1 than BRCA1?
AB  - It has been over a decade since mutations in BRCA1 and BRCA2 were found to be
      associated with a small number of familial breast cancer cases. BRCA1 is a large
      protein that interacts with many other proteins that have diverse functions, so
      it has been a challenge to determine how defects in its function could lead to
      cancer. One particular protein, BARD1, seems to be an important regulator of the
      tumour-suppressor function of BRCA1, as well as acting as a tumour suppressor
      itself. BARD1 is indispensable for cell viability, so loss-of-function mutations
      are rare, but mutations and truncations that alter its function might be involved
      in the pathogenesis of breast cancer.

PMID- 16633367
TI  - Measuring response in a post-RECIST world: from black and white to shades of
      grey.
AB  - The unprecedented pace of therapeutic development in oncology has created a
      climate in which the traditional methods of evaluating agent activity might no
      longer be adequate. How is the field transitioning to new endpoints in early drug
      development and what are the difficulties in this transition? Here, we will
      explore the historical context for the current criteria for tumour response
      evaluation and some of the pitfalls in using these standards when testing newer
      anticancer agents for activity. We will argue that the current drug development
      environment dictates different outcome measurements and therefore more
      imaginative and rigorous early-phase trial designs.

PMID- 16633368
TI  - Rosuvastatin treatment protects against nitrate-induced oxidative stress in eNOS
      knockout mice: implication of the NAD(P)H oxidase pathway.
AB  - Nitrate tolerance is associated with an enhanced superoxide anion (O(2)(-))
      production and may be attenuated by statins as they interact with the two main
      endothelial NO synthase (eNOS) and NAD(P)H oxidase pathways involved in this
      oxidative stress. Groups of wild-type (wt, C57Bl/6J) and eNOS knock-out mice
      (eNOS(-/-)) received rosuvastatin (20 mg kg(-1) day(-1) p.o.) for 5 weeks and a
      cotreatment with the statin plus nitroglycerin (NTG; 30 mg kg(-1) day(-1),
      subcutaneous injections b.i.d.) for the last 4 days. Another group received only
      NTG (30 mg kg(-1) d(-1), b.i.d. for 4 days) and finally control mice from both
      strains received no treatment. Rings of thoracic aortas from these groups were
      studied in organ baths. Relaxations to NTG (0.1 nM-0.1 mM) were determined on
      thromboxane analogue (U44619)-precontracted rings and O(2)(-) production (RLU 5
      s(-1) mg(-1) of total protein content) was assessed in aorta homogenates with the
      lucigenin-enhanced chemiluminescence technique. Reverse transcriptase-polymerase
      chain reaction analysis was performed on aortas from both mice strains. In vivo
      NTG treatment induced a significant rightward shift of the concentration-effect
      curve to NTG compared to control group. There was, however, no cross-tolerance
      with non-nitrate sources of NO (unaltered response to acetylcholine in wt group).
      The rosuvastatin + NTG cotreatment was able to protect against the development of
      nitrate tolerance in both mice strains and L-mevalonate abolished this protective
      effect of rosuvastatin. In vivo treatment with apocynin, a purported NAD(P)H
      oxidase inhibitor, also produced a similar protection to that observed with
      rosuvastatin in both strains. Superoxide anion formation was increased after NTG
      treatment in both mice strains and the rosuvastatin + NTG cotreatment was able to
      reduce that production. Moreover, rosuvastatin treatment abolished the increase
      in gp91phox mRNA (an endothelial membrane NAD(P)H oxidase subunit) expression
      induced by in vivo exposure to NTG. These findings suggest that long-term
      rosuvastatin treatment protects against nitrate tolerance by counteracting NTG
      induced increase in O(2)(-) production, probably via a direct interaction with
      the NAD(P)H oxidase pathway.

PMID- 16633369
TI  - Plasma selenium concentration and glutathione peroxidase activity in HIV-1/AIDS
      infected patients: a correlation with the disease progression.
AB  - AIMS AND OBJECTIVES: To find a correlation, if any, between the concentration of
      plasma selenium and erythrocyte activity in HIV-infected patients with the
      progression of the disease. MATERIALS AND METHODS: Plasma selenium concentration
      and erythrocyte glutathione peroxidase (GSH-Px) activity were measured in 62 HIV
      1 seropositive patients before commencing antiretroviral drug. Thirty (30) age
      matched and apparently healthy HIV-1/11 seronegative subjects were recruited as
      control subjects. HIV-1 seropositive patients were classified according to the
      Centre for Disease Control and Prevention (CDC) Criteria. RESULTS: The mean
      plasma selenium concentrations of 0.53+/-0.06_mol/L and 0.71+/-0.10_mol/L were
      significantly reduced (P<0.001) in HIV- 1 patients with CD4+ count of <200
      lym/mm3 and that of 200-499 lym/mm3 respectively when compared with the controls
      which is 1.01+/-0.10_mol/L. The mean erythrocyte GSH-Px activity of 15.1+/-2.4
      U/g Hb and 20.7+/-3.7U/g Hb of HIV-1 seropositive patients with CD4+ count of
      <200 lym/mm3 and 200-499 lym/mm3 respectively were significantly reduced
      (P<0.001) compared with 31.5+/-4.5 U/g Hb for the control. Our results clearly
      show that there is reduced scavenging antioxidant i.e Selenium and GSH-Px which
      will lead to oxidative stress in the HIV-1 patients when compared with controls,
      and decrease significantly with the progression of disease, i.e.
      AIDS<symptomatics<asymptomatics<controls. HIV-1 subtype variants have no
      significant influence in both parameters. CONCLUSION: The inclusion of selenium
      micronutrient which is essential for the activity of erythrocyte GSH-Px as an
      adjuvant in the management of HIV seropositive patients to prevent additional
      damage that can be caused by free radicals will be of immense benefit.

PMID- 16633370
TI  - Seroprevalence of HIV among male prisoners in Lagos State, Nigeria.
AB  - OBJECTIVE: To determine the seroprevalence of HIV I & II antibodies among
      prisoners in Lagos State. PATIENTS & METHODS: A total of 300 male prisoners from
      Kirikiri Maximum and Medium security prisons and Ikoyi prisons had their blood
      samples screened for antibodies against human immunodeficiency virus (HIV) types
      I & II by ELISA-based technique using immunocomb II HIV I & II Bispot kits.
      Samples that were positive were confirmed by another ELISA-based technique using
      immunocomb I & II combifirm kits. RESULTS: The seroprevalence of HIV antibodies
      was 6.7, which translated to 20 of the 300 prisoners screened. Only one (0.3) of
      the prisoners had HIV II infection, the rest being due to HIV I. There was no
      prisoner with concomitant HIV I & II infection. The age groups 20-29 and 30-39
      were most affected. CONCLUSION: The finding of 6.7 as prevalence in this study,
      which is slightly higher than the national prevalence in the year 2000 confirms
      that there may be activities in the prisons that increase the risk of acquiring
      HIV infection.

PMID- 16633371
TI  - The effects of birth interval on the birthweights of consecutive, same-sex term
      siblings.
AB  - OBJECTIVE: To investigate the effect of birth interval on the relationship
      between the birthweights of successive siblings. METHODS: The records of women
      who had delivered two consecutive, same-sex, live, singletons babies (1983
      through 1997) in a private hospital were analysed. The intervals between the
      birth dates of the siblings were calculated. The first of the siblings was coded
      Set A and the second, Set B. The ratios of the birthweights (Set B/Set A) were
      calculated. Comparison of findings was made between various ranges of birth
      interval. RESULTS: The birth interval band 24-29 months was associated with the
      highest mean birthweight for Set B babies and the highest birthweight ratio
      (p=0.016). Set A babies weighing less than 3000 g were most likely to be
      outweighed by their Set B siblings (p=0.000001). CONCLUSION: Birth intervals of
      24 to 29 months and small size of Set A babies were associated with most
      significant advantages in birthweight for Set B siblings.

PMID- 16633372
TI  - The Zaria Colobelt and bag.
AB  - The Zaria Colobelt and bag is an improvised aesthetic, functional, cheap,
      affordable and reusable colostomy appliance for the bulky high fiber stool of the
      African. It is made from cotton, polyethylene mackintosh and a bag. The device is
      useful in developing countries where colostomy bags are not easily available or
      affordable when available. The appliance protects the surgical wound from faecal
      soiling, improves on postoperative cough effort, and the bag can hold 900 g of
      liquid or semi-solid stool.

PMID- 16633373
TI  - Body mass index in type 2 diabetes mellitus complications: hypertensive diabetics
      and diabetic nephropathy.
AB  - BACKGROUND: It is widely reported that obesity is one of the major risk factors
      for developing type 2 Diabetes Mellitus, and also carries with it a higher risk
      of diabetic complications. OBJECTIVE: Body Mass Index was examined in type 2
      diabetes mellitus complications and the prevalence of overweight and obesity were
      determined. PATIENTS AND METHODS: fifty-two type 2 diabetic patients were
      studied. 13 patients with diabetic nephropathy, 16 were hypertensive diabetics
      while 23 were normotensive diabetics. The weight, height and blood pressure of
      the patients were measured and the BMI were calculated. RESULTS: The mean BMI was
      highest in the diabetic nephropathy patients (27.9+/-1.0) and lowest in the
      hypertensive diabetics (25.5+/-5.2) P=0.0001. The prevalence of overweight and
      obesity were 31 and 46 respectively in diabetic nephropathy compared with 19 and
      12.5 respectively in diabetics with hypertension. CONCLUSION: Overweight and
      obesity are more common in diabetics with nephropathy compared with normotensive
      and hypertensive diabetic patients.

PMID- 16633374
TI  - Comparison of the accuracy of trans-abdominal sonography (TAS) and transperineal
      sonography (TPS) in the diagnosis of Placenta Praevia.
AB  - BACKGROUND: Although the incidence of Placenta Praevia (PP) is low, its
      association with increased perinatal and maternal morbidity and mortality
      underscores the imperative of accurate pre-labour diagnosis. OBJECTIVE: To
      compare through a prospective study, the accuracy, sensitivity and specificity of
      Trans-Abdominal Sonography (TAS) and Trans-Perineal Sonography (TPS) in the
      diagnosis of Placenta Praevia and to determine the causes, if any, of avoidable
      diagnostic errors. METHODS: During the study period from 1999 to 2001, 133
      patients were evaluated by TAS and TPS. The age ranged from 19-41 years while the
      gestational age ranged from 20-weeks to term. All had examination with 3.5 MHz
      mechanical sector real-time scanner (Siemens high-resolution Sonoline SL-1
      ultrasound machine). The accuracy of TAS and TPS in diagnosing PP was then
      compared with surgical outcome in each patient. RESULTS: Out of the 133 patients
      diagnosed to have PP early on in pregnancy, 41 (30.8%) had persistent praevia
      till delivery, while in 92 (69.2%), the placenta converted to a normal location.
      The diagnosis at delivery confirmed the TPS diagnosis in 40 of 41 cases, while
      TAS diagnosis was confirmed in 39 of 41. TPS did not predict the delivery
      diagnosis in 1 patient where it ruled out a PP, TAS did not predict the delivery
      diagnosis in 2 patients who were believed not to have a clinically significant
      placenta praevia. In 1 patient TAS suggested PP but delivery diagnosis showed a
      normal placental implantation. The overall accuracy, specificity and sensitivity
      for TPS and TAS were 99.3%, 100%, 99.2% and 97.7%, 98.9%, and 95.1% respectively.
      CONCLUSION: TPS is a safe, accurate and rapid technique, which complement TAS for
      evaluation of patients with PP. In patients who decline this method however,
      graded bladder distension, Trendelenburg and traction scanning and determination
      of the absence of focal uterine contraction, which distorts the lower uterine
      segment, are techniques, which significantly improve the diagnosis of PP by TAS.

PMID- 16633375
TI  - Internal jugular and subclavian catheterisation: indications, problems and
      prospects in a Nigerian dialysis centre.
AB  - AIMS AND OBJECTIVES: To highlight the indications, problems and prospects of
      bedside non-surgically inserted jugular and subclavian dual lumen catheters.
      PATIENTS AND METHODS: Renal failure patients being managed in our centre with
      indications for central catheterisation were consecutively recruited at
      presentation. They had bedside non-surgical jugular and subclavian insertion of
      central catheters using modified Seldinger wire technique and the performance of
      the catheters monitored. RESULTS: Sixteen patients aged between 23 and 65 years
      had 32 central catheterizations during the 12-month period. The indications
      included its use as haemodialysis access in all catheterisations, additional
      indications were CVP monitoring in 5, and parenteral hyperalimentation in 1.
      Three catheterisations were in right subclavian vein, 4 in left internal jugular
      vein and 25 in right internal jugular vein. The duration of use ranged between 3
      days and 11 weeks and blood flow rate used ranged between 250 and 350 mls/min.
      Nine (28.1%) catheterisations were complicated with exit site and systemic
      infection. Catheter blockage and accidental catheter removal were recorded in 3
      patients each. Carotid artery puncture was recorded in 2 patients but haemostasis
      was maintained with direct digital compression. CONCLUSION: We conclude that
      percutaneous bedside internal jugular and subclavian (venous) catheterisation
      using dual lumen catheter is safe and devoid of major complications.

PMID- 16633376
TI  - Reference interval of serum heat-stable alkaline phosphatase activity in pregnant
      women in Zaria.
AB  - The study was designed to establish a reference interval for serum heat-stable
      ALP activity in pregnancy, which is not available in this environment. MATERIALS
      AND METHODS: One hundred (100) apparently healthy pregnant women in their third
      (3rd) trimester who were attending the antenatal clinic (ANC) of Ahmadu Bello
      University Teaching Hospital (ABUTH), Zaria were recruited for the study. The
      serum heat-stable ALP activity was measured using the 4-nitrophenyl phosphate (4
      NPP) method introduced in 1946 by Bessey, Lowry and Brock. RESULTS: The reference
      interval for the serum heat-stable ALP activity was found to be 24-161 IU/L. This
      was similar to some earlier reports elsewhere. CONCLUSION: The finding will help
      in the evaluation/diagnosis of patients with placental insufficiency.

PMID- 16633377
TI  - A clinicopathological analysis of the efficacy of lodoxamide 0.1% eye drops on
      the conjunctiva of patients with vernal keratoconjunctivitis seen at Guinness Eye
      Centre, Lagos University Teaching Hospital.
AB  - OBJECTIVE: To ascertain the efficacy of Lodoxamide 0.1 in the reduction of
      Clinicopathological signs of the conjunctiva in Vernal Keratoconjunctivitis.
      STUDY DESIGN: Prospective, non-comparative, Convenient Interventional Case
      Series. PARTICIPANTS: One Hundred consecutive patients; 57 males and 43 females
      within age range 2-55 years diagnosed with active and untreated Vernal
      conjunctivitis were enrolled. Approval was obtained from Ethical committee of
      Lagos University Teaching Hospital, Idi- Araba, Lagos. METHODS: Patients were
      given a bottle of Lodoxamide 0.1 each to instill four times daily into both eyes.
      Pre-treatment Clinical photographs and conjunctival biopsies were taken in 15
      volunteered patients. Ocular signs and symptoms were evaluated on day 1
      (baseline), days 2-3 (Interim) and then weekly for 6 weeks (final). Post
      treatment Clinical photographs and conjunctival biopsies were done at the 6th
      week. The conjunctival tissues were fixed for 24 hours in 10 Neutral buffered
      formalin prior to paraffin wax embedding and routinely stained with Haematoxylin
      and Eosin (H & E) stains. MAIN OUTCOME MEASURE: Primary outcome was based on the
      reduction of inflammatory cells especially the eosinophils on histological
      micrographs. Secondary efficacy was based on the rate and extent of reduction of
      the severity scores of the clinical signs and symptoms. RESULTS: Lodoxamide 0.1
      ophthalmic solution significantly reduced the density of the inflammatory cells
      especially eosinophils in the post treatment conjunctival biopsy cytology
      specimen. The mean physician severity scores for signs and symptoms consistently
      reduced from 72 hours of commencement of Lodoxamide with remarkable improvement
      in a week and complete resolution of all parameters at the end of 5th week.
      CONCLUSION: Lodoxamide 0.1 ophthalmic solution is highly effective in alleviating
      the clinical signs and symptoms of Vernal Keratoconjunctivitis and its
      antiallergic activity is exerted by inhibiting migration of inflammatory cells
      mainly eosinophlis.

PMID- 16633378
TI  - Histopathological study of liver diseases at the Lagos University Teaching
      Hospital, Nigeria (1989-2000).
AB  - OBJECTIVE: We present a retrospective histopathological study of 345 liver
      biopsies over a 12-year period. The study sought to record the frequencies of the
      range of histopathological changes observed in liver biopsy specimens. MATERIALS
      AND METHODS: the materials consisted of slides and paraffin embedded blocks of
      all liver biopsy specimens received from within and outside the hospital. The
      clinical data such as the age, sex, and clinical summary were extracted from the
      request forms. RESULTS: there were 222 males and 123 females; M: F=1.8:1; peak
      age incidence of 41-50 years. The three common histopathological diagnoses were
      hepatocellular carcinoma-33%, chronic hepatitis-17.7%, and liver cirrhosis-17.7%.
      Thirty per cent of hepatocellular carcinoma was post-cirrhotic. The peak age
      incidence of chronic hepatitis precedes that of liver cirrhosis and
      hepatocellular carcinoma by one decade. CONCLUSION: the common forms of liver
      disease diagnosed histologically are hepatocellular carcinoma, chronic hepatitis
      and liver cirrhosis. The age and sex distribution are similar to those already
      established in the African literature.

PMID- 16633379
TI  - Clinical and prognostic features of Nigerians with chronic myeloid leukemia.
AB  - AIMS AND OBJECTIVES: Chronic myeloid leukemia (CML). PATIENTS AND METHODS: CML
      patients confirmed at the OAUTHC, Ile-Ife between June 1986 and December 1999
      were studied prospectively until death or the last visit to the clinic. Stages of
      the disease at diagnosis, presenting clinical features and laboratory parameters,
      as well as the drug history were noted for each patient. Survival of each patient
      was computed from the date of diagnosis until the date of death. Kaplan-Meier
      statistical technique was used for analysis of survival. Factors were compared
      with log rank test. Student's t-test was used for comparing means of presenting
      clinical and laboratory parameters between groups. P-value of <0.05 was
      considered significant. SPSS for windows Release 10 (Real Stats, Real Easy, 1989
      1999) was used for all calculations. RESULTS AND CONCLUSION: There were 42
      patients (27 males and 15 females, ratio of 1.8:1) with ages ranging from 12-74
      (median=38.0) years. Philadelphia chromosome was positive in the five patients
      (12.0%) that underwent cytogenetic analysis. Thirty-three of the patients (78.6%)
      presented in treatable chronic phase and the other 9 (21.4%) were seen in
      advanced stages (7 in accelerated & 2 in blastic phase). The median survival of
      patients that presented in chronic phase was 31.7 months compared to 0.16 months
      in patients presenting in advanced stages, the difference was statistically
      significant (log rank=7.8, p-value=0.005). Significant positive correlation was
      obtained between spleen size and total white cell count at diagnosis (r=0.36,
      p=0.02). Univariate regression analysis showed negative relationship between
      survival and ages of patients at diagnosis, haematocrit value, spleen and liver
      sizes, and blast count. The relationships were statistically significant for only
      liver and spleen (b=-0.63, p=0.004 and b=-0.51, p=0.026, respectively).
      Regression of both the liver and spleen with survival, still confirms the
      significant negative relationship between hepatomegaly and survival.

PMID- 16633380
TI  - Pattern of chronic diarrhoea in children: a prospective analysis of causes,
      clinical features and outcome.
AB  - OBJECTIVES: To determine the pattern of chronic diarrhoea in children in Oman.
      STUDY DESIGN: This is a prospective study carried out over a 7 year period at the
      Sultan Qaboos University Hospital, Muscat, Oman. SUBJECTS: Sixty two children (37
      M:25 F), aged 3 months to 13 years who presented with chronic diarrhoea, defined
      as diarrhoea persisting for more than 4 weeks, were studied. RESULTS: Principal
      identifiable causes in the study population include post-gastroenteritis syndrome
      in 50% of cases, enteric infections and infestations in 27%, and coeliac disease
      in 13%. On presentation 63% were malnourished, 27% were anaemic while 39% were
      dehydrated. The median duration of hospital admission was 50 days. Majority of
      the patients responded to conservative therapy with correction of dehydration,
      and careful nutritional supplementation, in addition to specific therapy where
      necessary. Mortality was low (1.5%) resulting from immunodeficiency and gram
      negative septicaemia. CONCLUSION: Chronic diarrhoea remains an important cause of
      morbidity especially malnutrition in children and early and adequate nutritional
      rehabilitation plays a pivotal role in the management.

PMID- 16633381
TI  - Sonographic diagnosis of congenital brain malformations: the Ilorin experience.
AB  - A retrospective study was done to determine the incidence of congenital
      malformation of the brain among African infants over a 5 year period.
      Transfontanelle ultrasound (US) was performed on 98 infants consisting of 45
      males and 53 females. The mean age was 2.6 months (range 1-11 months). Congenital
      malformation was present in 25.5% of the 98 cases studied, most of which were
      associated with hydrocephalus. Cerebral aqueduct stenosis was the commonest
      congenital anomaly encountered and was found in 24% of case. This study shows
      that transfontanelle US is a useful tool for diagnosis of congenital brain
      malformations in infants.

PMID- 16633382
TI  - Anorectal anomaly: a review of 82 cases seen at JUTH, Nigeria.
AB  - BACKGROUND: The management of anorectal anomaly remains a challenge to Surgeons.
      This study was carried out to determine the pattern and outcome of management of
      anorectal malformations (ARM) in a Nigerian tertiary hospital. PATIENTS AND
      METHODS: The clinical and operative records of consecutive children with
      anorectal anomaly managed between October 1990 and September 2000 at the Jos
      University Teaching Hospital, Jos, were reviewed. RESULTS: There were 82
      patients, (57.3%) males and 35 (42.3%) females (m:f=1.3:1). There were 20 (24.4%)
      cases each of the high and intermediate types, 40 (48.8%) low variety and 2
      (2.4%) cases of persistent cloaca. The high type was proportionately commoner in
      the males. Less than one-third presented within 24 hours. Eighty three percent of
      patients (mainly males) presented in acute intestinal obstruction. Passage of
      stools from abnormal sites and "imperforate" anus were complaints in 60 (73.1%)
      patients each. A total of 63 patients had definitive corrective procedure. Four
      patients with stenotic anus were treated by serial anal dilatations while 29 with
      low anomaly had anoplasty during the neonatal period. Twenty eight patients with
      intermediate or high anomalies or persistent cloaca had definitive repair or pull
      through operations carried out 6-12 months after an initial colostomy. The
      definitive pull-through operations included abdominoperineal pull-through in 11
      patients, PSARP in 15, while 2 girls with persistent cloaca had posterior
      sagittal anorectovaginoure-throplasty (PSARVUP). Twenty nine children were fully
      continent of stools after surgery; three patients developed occasional faecal
      soiling; while six patients had faecal incontinence. CONCLUSION: Anorectal
      anomaly is common, but presentation is late in our environment. Although
      mortality rate was high (26%), early results of definitive operation among
      survivors were generally good after a mean follow-up period of 19 months.

PMID- 16633383
TI  - Burn scar carcinoma: two case reports and review of literature.
AB  - The development of carcinoma within a burn scar is an uncommon sequelae. When it
      does occur, the diagnosis is often delayed and consequently outcome less
      favourable. We present two cases seen and review existing literature on the
      aetiology, diagnosis and treatment of this problem. Delay in presentation and
      treatment is often the norm rather than the exception in this part of the world.
      We recommend early closure of all burn wounds and frequent biopsies of chronic
      leg ulcers.

PMID- 16633384
TI  - Solitary intracranial tuberculoma in patients without immuno-suppression: a
      report of three cases.
AB  - BACKGROUND AND OBJECTIVE: Poverty, drug resistance and the advent of human
      immunodeficiency virus infection (HIV) have led to a recent upsurge in the
      incidence of tuberculosis including intracranial tuberculosis. In this article,
      we report 3 patients who had solitary brain tuberculomas and were otherwise
      healthy to underscore the importance of continuing vigilance for this disease.
      CASE REPORTS: Three patients (57 years, female; 52 years, male; 7 years male)
      presented to our unit with features of intracranial tumours. They were all HIV
      negative with no previous history of tuberculosis. Cranial computed tomography
      scans demonstrated uniformly contrast enhancing falcine supratentorial masses in
      the adult patients and a cerebellar hemispheric lesion with peripheral contrast
      enhancement in the paediatric patient INTERVENTION: All the patients had gross
      total tumour excision. The histology confirmed a tuberculoma. They all had
      antituberculous therapy after histological confirmation. The outcome was good in
      all the patients. CONCLUSION: Intracranial tuberculoma can occur in otherwise
      healthy individuals and should always be considered in the differential diagnosis
      of solitary intracranial mass lesions in sub-Saharan Africans so that minimally
      invasive procedures can be used to establish the correct diagnosis.

PMID- 16633385
TI  - The frequency of twinning in a rural community in Western Nigeria--an update.

PMID- 16633386
TI  - Early recognition and early access for acute coronary syndromes in New Zealand:
      key links in the chain of survival.
AB  - AIMS: We studied the behaviour of patients prior to admission to hospital with
      symptoms of acute coronary syndromes, and what barriers may exist to early
      recognition of these symptoms and to early activation of emergency medical
      services. METHODS: Over a 7-week period, we interviewed 100 patients admitted to
      the Cardiac Care Unit in Wellington Hospital with suspected acute coronary
      syndromes. RESULTS: Within 5 minutes of symptom onset, 46 of 100 patients
      believed they were having a heart attack. Sixty-two of the patients believed that
      they had a cardiac-related problem. Patients took a median time of 90 minutes
      (range 0-9600 minutes) to contact a health professional from the time of symptom
      onset; and a median time of 228 minutes (range 33-9633 minutes) to arrive at
      hospital. We observed significant differences in both these end-points according
      to which health professional was contacted first. Patients who presented directly
      to hospital arrived significantly faster (median 72 minutes) than those who first
      called an ambulance (180 minutes) or contacted a general practitioner (485
      minutes) (p=0.001, Kruskal Wallis test). CONCLUSIONS: Considerable delays exist
      in the presentation of patients with symptoms of ACS to hospital. These delays
      are multifactorial, but the psychological intimidation of the 111 telephone
      system and delays incurred by inappropriate out-of-hospital management of
      patients with chest pain are probably significant. It is likely that these delays
      contribute to mortality from acute coronary syndromes.

PMID- 16633387
TI  - Foville's syndrome masquerading as Wernicke's encephalopathy.

PMID- 16633388
TI  - Cardiovascular risk factors and their associations with alcohol consumption: are
      there differences between Maori and non-Maori in Aotearoa (New Zealand)?
AB  - AIMS: To describe the relationship between indicators of alcohol consumption and
      major known cardiovascular risk factors, and to test whether these relationships
      are different for Maori and non-Maori. METHODS: Data from five New Zealand
      studies (national and population specific) conducted since 1988 were made
      available to the investigators and were re-analysed by Maori and non-Maori
      classification using multivariate modelling adjusting for sex and age. Three
      indicators of alcohol consumption were used: frequency of drinking, volume drunk
      on a typical or usual occasion, and average daily consumption. Interaction terms
      were used to test for differences between Maori and non-Maori in the associations
      between alcohol consumption and cardiovascular risk factors (tobacco smoking,
      systolic and diastolic blood pressure, high density lipoprotein (HDL), the ratio
      of total cholesterol to HDL, serum glucose, reported diagnosis of diabetes, and
      body mass index). RESULTS: There were a total of 44,830 people in the combined
      study populations of whom 6926 (15.4%) were Maori. For the risk factors examined,
      in general Maori had higher levels of risk compared to non-Maori. The pattern of
      associations between each of the three indicators of alcohol consumption and
      lipid factors, diabetes, serum glucose level, and obesity were not shown to be
      different in Maori and non-Maori. However for systolic blood pressure and tobacco
      smoking, the patterns of association were different. CONCLUSION: There are clear
      associations for most of the cardiovascular risk factors examined and alcohol
      consumption. These associations are consistent for Maori and non-Maori, except
      for blood pressure and cigarette smoking. As the study is hypothesis-generating,
      further investigation is required for confirmation.

PMID- 16633389
TI  - Oral angioedema secondary to ACE inhibitors, a frequently overlooked association:
      case report and review.

PMID- 16633390
TI  - Secondhand tobacco smoke exposure in New Zealand bars: results prior to
      implementation of the bar smoking ban.
AB  - AIMS: To measure secondhand smoke (SHS) levels in New Zealand bars prior to
      smokefree legislation enacted on 10 December 2004. METHODS: Thirty bars were
      randomly selected from urban, surburban, and surrounding rural areas of Auckland,
      Wellington, and Invercargill. Bars were visited (on a Friday or Saturday night
      for a 3-hour stay between 1800 and 2400 hours) in July/August/September 2004
      (winter) and again in October/November 2004 (spring). Each bar was visited by a
      group of 4 or 5 non-smokers participating in the study. All groups of
      participants spent a 3-hour block of continuous time in the bar. Saliva samples
      (approximately 0.5-2 mL) were provided immediately prior to entering the bar as
      well as 5-15 minutes after leaving the bar. Each group recorded the initial
      impression of air quality and ventilation, the number of observed lit cigarettes
      over three 10-minute intervals throughout the evening, and the number of patrons
      at each interval. In addition, any general comments about the venue (relevant to
      bar attendance or air quality on the evening) was recorded. Cotinine, the main
      metabolite of nicotine, was measured in saliva samples using Liquid
      Chromatography with tandem Mass Spectrometry (LC-MS-MS). RESULTS: In all bars,
      and in all volunteers, exposure to SHS was evident. Saliva cotinine increased
      after 3 hours in the bar (mean increase=0.66 ng/mL, SE=0.03 ng/mL, p value of
      <0.0001). The 30 bars randomly selected provided a good spectrum of SHS
      exposures, with mean cotinine increasing by approximately 8-fold. Smaller
      population centres showed greater exposures to SHS. A north-south gradient of
      exposure was also seen (highest exposures were in Southland). Higher exposures
      were seen in the winter than in the spring. The objective measures of SHS
      exposure correlated strongly with the volunteers' subjective observation of
      ventilation, air quality, and counts of lit cigarettes. One exception was where
      objective salivary markers indicated that even "seemingly smokefree" venues with
      "good ventilation" produced discernable levels of SHS exposure. CONCLUSIONS: We
      have utilised an objective, non-invasive scientific approach to assess SHS smoke
      exposure in patrons of New Zealand bars. Our results clearly indicate exposure to
      SHS, with regional and seasonal variation, prior to the introduction of smokefree
      legislation.

PMID- 16633391
TI  - How low can it go? Projecting ischaemic heart disease mortality in New Zealand to
      2015.
AB  - AIMS: This study aims to identify how ischaemic heart disease (IHD) mortality
      rates in New Zealand have varied between successive cohorts and time periods.
      This information is then used to project IHD mortality rates and counts (burdens)
      out to year 2011-15. METHODS: Age/period/cohort models were constructed (5-year
      periods and 5-year age groups, generating 10-year overlapping cohorts) using both
      frequentist and Bayesian methods. Data were available from 1956 for the total
      population and from 1981 for Maori. The projection period was 2001-5 to 2011-15.
      Uncertainty was quantified as the Bayesian 90% credible interval. RESULTS: IHD
      mortality rates for all age by gender groups increased from 1956-60 to peak in
      1966-70, then declined by more than 60% to current (1996-2000) levels. However,
      the decline has been much shallower for Maori. This decline has resulted from
      increasingly favourable period effects since 1971-75 (less marked for Maori).
      However, no substantive cohort effects have been seen, at least from the 1891 to
      the 1951 cohort. Our model suggests that, for the first time, a substantive and
      unfavourable cohort effect may be emerging among recent birth cohorts.
      CONCLUSIONS: IHD mortality rates are projected to continue to fall from 2001-05
      to 2011-15, albeit more slowly than in the past as the increasing (favourable)
      period effect is partly offset by an emerging (unfavourable) cohort effect. The
      result is a relatively small projected decline in absolute IHD mortality burden
      overall, but an actual increase among Maori.

PMID- 16633392
TI  - New Zealand health professionals do not agree about what defines appropriate
      attendance at an emergency department.
AB  - AIMS: Emergency Departments (EDs) worldwide are facing a crisis from overcrowding
      -a common perception exists that inappropriate use of the ED is the major
      contributing factor. This study aims to examine the concept of 'inappropriate' ED
      attendances in relation to the Emergency Department at New Zealand's Christchurch
      Hospital. It specifically seeks to determine whether there is a consensus opinion
      among healthcare providers regarding a definition of 'inappropriate'. METHODS: An
      exploratory survey of health professionals involved with the referral,
      assessment, transport, and treatment of ED patients in Christchurch was carried
      out. A range of health professionals, including ambulance personnel, general
      practitioners, emergency department physicians, emergency nurses, and hospital
      managers were approached. A series of questions relating to definition and
      response to 'inappropriate' patients was asked, with an additional open-ended
      question relating to the definition of 'appropriateness'. RESULTS: There are
      significant differences in the attitudes and perceptions of key health
      professionals involved in the referral, treatment, and admission of patients to
      the ED. CONCLUSIONS: While there are some areas of general agreement, there is no
      clear consensus between the professionals surveyed regarding the concept of
      'appropriateness.' This has implications for any interventions aimed at
      addressing ED 'overcrowding' that assume the presence of a consensus
      understanding of this concept.

PMID- 16633393
TI  - Nutritional information about sodium: is it worth its salt?
AB  - This study examined whether members of the general public were able to accurately
      interpret the nutritional information regarding salt on the packaging of food
      products. 226 participants answered brief questions about their salt intake
      awareness and were asked to estimate the salt content of a food product, using
      the nutritional information panel on the packaging as required. Results indicated
      that most participants did not know how to interpret the nutritional information,
      and that many underestimated the salt content of the product by confusing it with
      sodium content. This finding suggests that the sodium information on packaged
      foods in New Zealand is not easily understood by the target population, and is
      therefore of little use in its current form.

PMID- 16633394
TI  - Estimated prevalence of cardiovascular disease and distribution of cardiovascular
      risk in New Zealanders: data for healthcare planners, funders, and providers.
AB  - AIMS: New Zealand cardiovascular risk management guidelines advocate targeted
      risk assessment based primarily on age, gender, and ethnicity--and recommend drug
      management for people with a 5-year absolute cardiovascular disease (CVD) risk
      greater than 15%. To inform service planning and healthcare delivery for district
      health boards and primary healthcare organisations in New Zealand, we have
      produced population estimates of CVD prevalence and 5-year absolute CVD risk.
      METHODS: The 1993 Auckland Heart and Health Study provided the data for
      estimating CVD prevalence and absolute CVD risk distributions using the
      Framingham CVD risk prediction equation. These estimates were applied to
      population projections for 2005 based on 2001 New Zealand Census data. RESULTS:
      Of the projected 2.09 million people aged over 35 years in New Zealand in 2005,
      approximately 1.5 million (72%) meet national criteria for formal CVD risk
      assessment. About 151,000 (7%) are estimated to have suffered a non-fatal heart
      attack or stroke or have angina. A further 262,000 (13%) are estimated to have a
      5-year CVD risk greater than 15% based on New Zealand CVD risk charts. This
      represents around 1 in 5 adults over the age of 35 years in New Zealand for whom
      pharmacological interventions are recommended according to the New Zealand CVD
      risk guidelines for the prevention of new or further CVD events. CONCLUSIONS: The
      latest published data available on the burden of CVD risk in New Zealand is now
      over 10 years old and does not include Maori, Pacific, and other non-European
      ethnic groups. Current data on the risk profile of adult New Zealanders is
      required for more accurate service planning. However the information reported
      here provides a reasonable estimate of the magnitude of the task. Although
      systematic identification and management of CVD risk in New Zealanders with
      raised CVD risk will be a major undertaking for healthcare services, it has the
      potential to produce significant health-gains while reducing health disparities.

PMID- 16633395
TI  - Heart health has an adverse future forecast in New Zealand: an alarm call to
      action across the continuum.

PMID- 16633396
TI  - Reducing salt intake: action beyond the label.

PMID- 16633397
TI  - Medical image. Differentiate hepatic abscess from simple cyst.

PMID- 16633398
TI  - Interferon beta, PHARMAC, and political directives: in the best interests of
      people with multiple sclerosis?
AB  - Interferon beta is prescribed for people with multiple sclerosis in an attempt to
      reduce the number of relapses occurring and to slow progression of disability.
      The current cost of the subsidy provided by PHARMAC for this drug is over NZ$5
      million annually and is likely to rise. The history of funding decisions for
      interferon beta, the evidence for cost-effectiveness of the drug, and other
      possible ways of improving outcomes for people with multiple sclerosis other than
      this particular pharmaceutical subsidy are considered in this article. The
      authors conclude that the evidence for cost-effectiveness of interferon beta is
      not compelling, and other options need to be considered in an integrated package
      of health services for all people with MS in New Zealand.

PMID- 16633399
TI  - Response to the article by Lynn et al: older patients in the nephrology clinic-
      should they be referred?

PMID- 16633400
TI  - Outcome measures in the management of chlamydial genital infection in New
      Zealand.

PMID- 16633402
TI  - Screening for pharyngeal Chlamydia trachomatis in asymptomatic men who have sex
      with men.

PMID- 16633403
TI  - Deep-etched high-density fused-silica transmission gratings with high efficiency
      at a wavelength of 1550 nm.
AB  - We describe the design, fabrication, and excellent performance of an optimized
      deep-etched high-density fused-silica transmission grating for use in dense
      wavelength division multiplexing (DWDM) systems. The fabricated optimized
      transmission grating exhibits an efficiency of 87.1% at a wavelength of 1550 nm.
      Inductively coupled plasma-etching technology was used to fabricate the grating.
      The deep-etched high-density fused-silica transmission grating is suitable for
      use in a DWDM system because of its high efficiency, low polarization-dependent
      loss, parallel demultiplexing, and stable optical performance. The fabricated
      deep-etched high-density fused-silica transmission gratings should play an
      important role in DWDM systems.

PMID- 16633404
TI  - Carambola optics for recycling of light.
AB  - Recycling of light allows the luminance (radiance) emitted by a light source to
      be increased at the cost of reducing the total luminous flux (radiant power).
      Recycling of light means returning part of the emitted light to the source, where
      part of it will escape absorption. An optical design that is suitable for
      multiple and controlled recycling is described. Carambola optics is named for its
      resemblance to star fruit. Several pairs of mirrors or prisms redirect light
      repeatedly onto the source, thus achieving multiple transits of the light through
      the source. This recycled light exits the carambola in the same phase space as
      light directly emitted and not recycled.

PMID- 16633405
TI  - Development of a multi-Fourier-transform interferometer: fundamentals.
AB  - We describe the development of an instrument that uses a Martin-Puplett-type
      Fourier-transform spectrometer to apply an aperture synthesis technique to
      millimeter and submillimeter waves. We call this instrument a multi-Fourier
      transform interferometer (MuFT). The MuFT performs wideband imaging,
      spectroscopy, and polarimetry, at millimeter and submillimeter wavelengths. We
      describe the fundamentals of the MuFT and give an example of one potential
      implementation. A full description of the observables with a MuFT is provided. A
      physical explanation of the observability of complex visibility by the MuFT is
      given. Fundamental restrictions on observations with the MuFT, e.g., limits on
      spectral and spatial resolution and on fields of view, are discussed. The
      advantages of the MuFT are summarized.

PMID- 16633406
TI  - Wavefront reconstruction by spatial-phase-shift imaging interferometry.
AB  - Common-path imaging interferometers offer some advantages over other
      interferometers, such as insensitivity to vibrations and the ability to be
      attached to any optical system to analyze an imaged wavefront. We introduce the
      spatial-phase-shift imaging interferometry technique for surface measurements and
      wavefront analysis in which different parts of the wavefront undergo certain
      manipulations in a certain plane along the optical axis. These manipulations
      replace the reference-beam phase shifting of existing interferometry methods. We
      present the mathematical algorithm for reconstructing the wavefront from the
      interference patterns and detail the optical considerations for implementing the
      optical system. We implemented the spatial phase shift into a working system and
      used it to measure a variety of objects. Measurement results and comparison with
      other measurement methods indicate that this approach improves measurement
      accuracy with respect to existing quantitative phase-measurement methods.

PMID- 16633407
TI  - Development of high-throughput, polarization-maintaining, near-field probes.
AB  - A novel, chemical-etching technique produces very high throughput, polarization
      maintaining probes for near-field, scanning, optical microscopy (NSOM). The
      process includes coating the tips with aluminum and forming the apertures with a
      focused ion beam (FIB). The elliptical core fibers used resulted in elliptical
      apertures for the probes. The throughput of the probes depends on the incident
      polarization. For polarization parallel to the minor axis, the tip presents an
      insertion loss of only 20 dB for aperture widths of 55 nm. Probes have a typical
      polarization extinction of 100 to 1 in the far field. These tips produced NSOM
      images of gold dots on a GaAs substrate in reflection mode.

PMID- 16633408
TI  - Reduced wavelength-dependent quarter-wave plate fabricated by a multilayered
      subwavelength structure.
AB  - We developed a novel fabrication method of a reduced wavelength-dependent quarter
      wave plate (QWP) based on form birefringence of a multilayered subwavelength
      structure. The multilayered structure was constructed by depositing a high
      refractive-index thin film on a subwavelength-structured substrate with a low
      refractive index. The surface structure of the substrate was shallow enough to be
      formed by a mass replication technology. A high-refractive-index subwavelength
      grating was formed on ridges of the substrate by sputtering Zn2SnO4 (refractive
      index of 2.03 at a wavelength of 633 nm). Moreover, since the grooves of the high
      refractive-index grating were very deep and narrow, the dispersion of form
      birefringence suppressed the dependency of phase retardance on the wavelength of
      light in a limited spectral region. The phase retardance of the fabricated QWP
      was 89 degrees at a 633 nm wavelength and 79 degrees at a 785 nm wavelength.

PMID- 16633409
TI  - Testing a fast off-axis parabolic mirror by using tilted null screens.
AB  - We propose the design of tilted null screens for testing off-axis segments of
      conic surfaces. The tilt allows us to control the size of the screen and the
      sensitivity of the test. For positive tilt angles the sensitivity is increased
      while the size of the screen is reduced in the sagittal caustic region and vice
      versa in the tangential caustic region. Further analysis and preliminary
      experimental results are presented for a fast off-axis concave parabolic mirror
      with an elliptical aperture. An offset distance of X(C) = 25.4 mm yields radius
      of curvature at the vertex R = 20.4 mm; major axis of the mirror D(M) = 49.4 mm;
      and minor axis D(m) = 29.5 mm.

PMID- 16633410
TI  - Photoconductive optically driven deformable membrane for spatial light modulator
      applications utilizing GaAs substrates.
AB  - The fabrication and characterization of an optically addressable deformable
      mirror for a spatial light modulator is described. Device operation utilizes an
      electrostatically driven pixellated aluminized polymeric membrane mirror
      supported above an optically controlled photoconductive GaAs substrate. A 5
      microm thick grid of patterned photoresist supports the 2 microm thick aluminized
      Mylar membrane. A conductive ZnO layer is placed on the back side of the GaAs
      wafer. A standard Michelson interferometer is used to measure mirror deformation
      data as a function of illumination, applied voltage, and frequency. A simplified
      analysis of device operation is also presented.

PMID- 16633411
TI  - White LED light coupling into light guides with diffraction gratings.
AB  - Radial diffractive gratings are used to couple light of a white LED into a light
      guide. Theoretical coupling efficiencies are evaluated with rigorous diffraction
      theory in a pure conical mounting. It is shown that when the refractive index of
      the grating increases from 1.46 to 2.05 the incoupling efficiency increases from
      42% to 63%. Also, with the increasing refractive index the incoupling efficiency
      is shown to become more nearly uniform over the visible spectrum. Experimental
      results for the incoupled efficiencies and the color coordinates of the incoupled
      spectra are introduced for refractive indices n=1.46 and n=1.56.

PMID- 16633412
TI  - Rayleigh scattering, absorption, and birefringence of large-size bulk single
      crystal sapphire.
AB  - While the thermomechanical properties of sapphire make it an excellent candidate
      of test mass for advanced laser interferometers, its optical quality is not well
      understood or well controlled. We have studied the results from high-resolution
      measurements of scattering, absorption, and birefringence in test-mass samples to
      better understand issues of quality. Samples show large-scale scattering
      structures clearly linked to the crystal-growth process. Samples characterized by
      the presence of point defects have significantly lower scattering (except at the
      point defects). In general on a large scale, high scattering also correlates with
      higher absorption and higher average birefringence inhomogeneity. However, on a
      smaller scale there is not a clear point-to-point correlation between scattering
      and absorption. Often a large-scale scattering structure is spatially displaced
      by tens of millimeters from a similar absorption structure, indicating that quite
      separate microscopic mechanisms give rise to scattering and absorption. The
      spatial displacements indicate that absorption centers and scattering centers are
      laid down during crystal growth at different distances from the solid-liquid
      interface. We suggest that absorption may be linked to F centers, while
      scattering may be linked to impurities such as iron.

PMID- 16633413
TI  - Double-deformable-mirror adaptive optics system for phase compensation.
AB  - Two kinds of algorithm for an adaptive optics (AO) system that uses two
      deformable mirrors (DMs), one with large stroke and the other with high spatial
      frequency, to correct different aberrations are described. The algorithms are
      based on modal method and direction-gradient method, respectively. Numerical
      simulations for the algorithms have been made. The simulation results indicate
      that the two DMs in the AO system can correct different aberrations with
      different characteristics, and the closed-loop performance of a double-DM AO
      system will be almost the same as that of an AO system that uses a single DM with
      an ideal stroke.

PMID- 16633414
TI  - Real-time photodisplacement microscope for high-sensitivity simultaneous surface
      and subsurface inspection.
AB  - We have developed a new photodisplacement microscope system for practical use
      that achieves high-sensitivity simultaneous real-time imaging of surface and
      subsurface structures from a single space-frequency multiplexed interferogram. In
      this system a linear region of photothermal displacement is excited on the sample
      surface for subsurface imaging by a line-focused intensity-modulated laser beam.
      Surface information such as reflectivity and topography along with the
      displacement is detected with a charge-coupled device sensor-based parallel
      heterodyne interferometer. Surface and subsurface information components are
      space-frequency multiplexed into the sensor signal as orthogonal functions based
      on a frequency-optimized undersampling scheme, allowing each to be discretely
      reproduced by using a real-time Fourier analysis technique. Preliminary
      experiments demonstrate that this system is effective, simultaneously imaging
      reflectivity, topography, and photodisplacement for the detection of subsurface
      lattice defects in silicon, at a remarkable speed of only 0.26 s/256x256 pixel
      area. This new microscope is promising for nondestructive hybrid surface and
      subsurface inspection and other applications.

PMID- 16633415
TI  - Diffraction of conic and Gaussian beams by a spiral phase plate.
AB  - An analytical expression for the spatial spectrum of the conic wave diffracted by
      a spiral phase plate (SPP) with arbitrary integer singularity of order n is
      obtained. Conic wave diffraction by the SPP is equivalent to plane-wave
      diffraction by a helical axicon. A comparison of the conic wave and Gaussian beam
      diffraction on a SPP is made. It is shown that in both cases a light ring is
      formed, with the intensity function growing in proportion to rho(2n) at small
      values of radial variable rho and decreasing as n(2)rho(-4) at large rho. By use
      of direct e-beam writing on the resist, a 32 level SPP of the 2nd order and
      diameter 5 mm is manufactured. By use of this SPP, a He-Ne laser beam is
      transformed into a beam with phase singularity and ringlike intensity
      distribution. A four-order binary diffractive optical element (DOE) with its
      transmittance proportional to a linear superposition of four angular harmonics is
      also manufactured. With this DOE, simultaneous optical trapping of several
      polystyrene beads of diameter 5 microm is performed.

PMID- 16633416
TI  - Holographic chiral structure on the basis of Weigert's effect.
AB  - A simple analysis of the possibility of creating a holographic chiral structure
      on the basis of Weigert's effect with help of the Jones vector-matrix method was
      done, to my knowledge, for the first time. A corresponding experiment was also
      conducted. The results of the investigation show that the diffractive optical
      element obtained behaves similarly to liquid crystals or sculptured thin films
      with chiral structures.

PMID- 16633417
TI  - Use of thresholding algorithms in the processing of raindrop imagery.
AB  - Several thresholding algorithms are applied to the analysis of drop images, and
      their performance is compared. Images were obtained by use of a digital camera
      setup in which drops were illuminated from behind, resulting in an image of the
      drop silhouette. Each algorithm was evaluated based on the accuracy of the drop
      diameter obtained from the thresholded image and on the size of the depth of
      field. Because of the difficulty associated with creating drops that have a known
      diameter, solid spheres composed of a glass with an index of refraction close to
      that of water were used in computing the depth of field and in determining the
      accuracy of measured diameter. The application of this study is to the automatic
      measurement of raindrops and images were obtained during several storms. With
      each thresholding algorithm this raindrop imagery was used to compute the
      probability density function of drop diameter, and the rain rate. The performance
      of each thresholding algorithm was quantified by comparison of these measurements
      with simultaneous measurements obtained by use of a Joss-Waldvogel disdrometer.

PMID- 16633418
TI  - Characteristics of pixel arrangements in various rhombuses for full-parallax
      three-dimensional image generation.
AB  - In full-parallax three-dimensional (3-D) imaging systems, the pixel cells often
      have the shape of a rhombus. Proper arrangement of pixels in these rhombic-shaped
      cells is important to maximize the quality of displayable 3-D images with a given
      display panel. The possible number of pixel arrangements in a rhombic cell with a
      definite dimension is found by considering the number of possible crossings
      between parallel line families forming the pixel cells, when the slopes of the
      lines are approximated by the ratio between the number of pixels in the vertical
      and horizontal directions. To make the rhombic cell have a uniquely defined pixel
      arrangement, its horizontal and vertical dimensions should be equal to the even
      multiple of the pixel dimension in their corresponding direction.

PMID- 16633419
TI  - Improved optimization of soft-partition-weighted-sum filters and their
      application to image restoration.
AB  - Soft-partition-weighted-sum (Soft-PWS) filters are a class of spatially adaptive
      moving-window filters for signal and image restoration. Their performance is
      shown to be promising. However, optimization of the Soft-PWS filters has received
      only limited attention. Earlier work focused on a stochastic-gradient method that
      is computationally prohibitive in many applications. We describe a novel radial
      basis function interpretation of the Soft-PWS filters and present an efficient
      optimization procedure. We apply the filters to the problem of noise reduction.
      The experimental results show that the Soft-PWS filter outperforms the standard
      partition-weighted-sum filter and the Wiener filter.

PMID- 16633420
TI  - Application of self-deconvolution method to shift-and-add solar imaging.
AB  - A shift-and-add (SAA) operation is conducted to reconstruct a high-spatial
      resolution image from atmospherically degraded solar images. The self
      deconvolving data reconstruction algorithm is used to augment high-spatial
      frequency components in solar speckle images and rectify the background component
      that results from the SAA operation. Self-deconvolved solar speckle images are
      shift and added and the resulting image shows high-spatial-resolution features.

PMID- 16633421
TI  - Branch cut surface placement for unwrapping of undersampled three-dimensional
      phase data: application to magnetic resonance imaging arterial flow mapping.
AB  - We demonstrate in both simulated and real cases the effect that undersampling of
      a three-dimensional (3D) wrapped phase distribution has on the geometry of phase
      singularity loops and their branch cut surfaces. The more intuitive two
      dimensional (2D) problem of setting branch cuts between dipole pairs is taken as
      a starting point, and then branch cut surfaces in flat and ambiguous 3D loops are
      discussed. It is shown that the correct 2D branch cuts and 3D branch cut surfaces
      should be placed where the gradient of the original phase distribution exceeded
      pi rad voxel(-1). This information, however, is lost owing to undersampling and
      cannot be recovered from the sampled wrapped phase distribution alone. As a
      consequence, empirical rules such as finding the surface of minimal area or
      methods based on the wrapped phase gradient will fail to find the correct branch
      cut surfaces. We conclude that additional information about the problem under
      study is therefore needed to produce correct branch cut surfaces that lead to an
      unwrapped phase distribution with minimum local errors. An example with real data
      is provided in which downsampled phase contrast magnetic resonance imaging data
      are successfully unwrapped when the position of the vessel walls and the physical
      properties of the flowing blood are taken into account.

PMID- 16633422
TI  - Optical frequency-modulated continuous-wave interferometers.
AB  - I discuss optical frequency-modulated continuous-wave (FMCW) interferometers,
      including their principles, characteristics, specific requirements, procedure for
      their construction, optical configurations, primary applications, optical
      sources, resolution, measurement range, and stability.

PMID- 16633423
TI  - Nonlinear equalization for holographic data storage systems.
AB  - Despite the fact that the channel in a holographic data-storage system is
      nonlinear, most of the existing approaches use linear equalization for data
      recovery. We present a novel and simple to implement nonlinear equalization
      approach based on a minimum mean-square-error criterion. We use a quadratic
      equalizer whose complexity is comparable to that of a linear equalizer. We also
      explore the effectiveness of a nonlinear equalization target as compared with the
      conventional linear target. Bit-error-rate (BER) performance is studied for
      channels having electronics noise, optical noise, and a different span of
      intersymbol interference. With a linear target, whereas the linear equalizer
      exhibits an error floor in the BER performance, the quadratic equalizer
      significantly improves the performance with no sign of error floor even up to 10(
      7). With a nonlinear target, whereas the quadratic equalizer provides an
      additional performance gain of 1-2 dB, the error-floor problem of the linear
      equalizer has been considerably alleviated, thereby significantly improving the
      latter's performance. A theoretical performance analysis of the nonlinear
      receiver with non-Gaussian noise is also presented. A simplified approach is
      developed to compute the underlying probability density functions, optimum
      detector threshold, and BER using the theoretical analysis. Numerical results
      show that the theoretical predictions agree well with simulations.

PMID- 16633424
TI  - Chromatic dispersion effects in analog polarization-modulated links.
AB  - The effect of chromatic dispersion on a photonic link employing polarization
      modulation is studied analytically and experimentally. For analog polarization
      modulation, dispersion introduces a frequency-dependent rotation to the
      orientation of modulation about the center of modulation. As a result, the
      dispersion-limited bandwidth of the link will depend on receiver design.

PMID- 16633425
TI  - Deep nulling of laser light with a single-mode-fiber beam combiner.
AB  - The detection of faint companions to bright stars requires the development of
      very-high-contrast-ratio detection techniques such as nulling interferometry.
      Here we present, to our knowledge, the first experimental test of a novel beam
      combination method, which is based on coupling the light at the center of a dual
      aperture interference pattern into a single-mode fiber. Using such a "fiber
      nuller" approach, a visible He-Ne laser has been stably nulled to as low as
      1.3x10(-6), thus validating the approach.

PMID- 16633426
TI  - Widely tunable optical bandpass filter by use of polymer long-period waveguide
      gratings.
AB  - We report the design and fabrication of a widely tunable optical bandpass filter
      based on using two identical long-period gratings formed along a polymer channel
      waveguide with a section of the waveguide core removed. The peak transmission of
      the passband of the fabricated filter is approximately 60% and the bandwidth of
      the passband is approximately 6 nm. The filter is thermally tunable over the C +
      L band (1520-1610 nm) for both TE and TM polarizations with a temperature control
      of approximately 30 degrees C.

PMID- 16633427
TI  - Laser-mode selection by a combination of biprism-like reflectors with narrow
      amplitude masks.
AB  - In recent work the laser mode selectivity induced separately by a biprism-like
      reflector and by an absorbing strip was investigated by numerical analysis. It
      was shown that each of these elements in an otherwise conventional resonator was
      suitable to cause the laser to oscillate preferentially on the first odd mode
      that contains a line singularity, which is a useful dark beam (i.e., a laser beam
      with a dark central region) for high-resolution metrological applications. We
      study the combined effect of these two mode-selecting elements and show that the
      unified analysis leads to much better performance than could be expected from a
      simple superposition of the performance with each element alone. The results
      indicate that the mode selectivity can be enhanced by at least a factor of 3
      compared with that of laser resonators with biprism-like reflectors alone. Thus a
      laser equipped with such a combined element will oscillate on a pure first-order
      mode with high power efficiency. Moreover, calculations show that the resultant
      dark beam, focused for metrological applications, has a significantly improved
      shape compared with the dark beam obtained by external modulation of a
      fundamental Gaussian beam.

PMID- 16633428
TI  - Terahertz birefringence and attenuation properties of wood and paper.
AB  - The far-infrared properties of spruce wood are examined with a terahertz time
      domain spectrometer. The solid wood is shown to exhibit both birefringence and
      diattenuation. The birefringence properties are sufficient for construction of a
      quarter-wave plate operating at 0.36 THz, and a half-wave plate operating at 0.71
      THz. The origin of the birefringence is attributed to preferential fiber
      orientation within the wood. Similar birefringence is observed in lens paper in
      which the fibers are preferentially oriented in one direction.

PMID- 16633429
TI  - Theoretical investigation of the off-axis z-scan technique for nonlinear optical
      refraction measurement.
AB  - The theoretical investigation of the off-axis z-scan technique for the
      measurement of nonlinear optical refraction in materials is presented. The
      normalized transmittance is calculated for different aperture radii and
      positions. The dependence of both the normalized transmittance amplitude
      (DeltaT(pv)) and the distance between maximum and minimum (Deltaz(pv)) on the
      aperture radius is analyzed. A condition for the applicability of the pinhole
      approximation is given.

PMID- 16633430
TI  - Integrated optical motor.
AB  - A light-driven micrometer-sized mechanical motor is created by laser-light
      induced two-photon photopolymerization. All necessary components of the engine
      are built upon a glass surface by an identical procedure and include the
      following: a rigid mechanical framework, a rotor freely rotating on an axis, and
      an integrated optical waveguide carrying the actuating light to the rotor. The
      resulting product is a most practical stand-alone system. The light introduced
      into the integrated optical waveguide input of the motor provides the driving
      force: neither optical tweezers or even a microscope are needed for the function.
      The power and efficiency of the motor are evaluated. The independent unit is
      expected to become an important component of more complex integrated lab-on-a
      chip devices.

PMID- 16633431
TI  - On-line simultaneous monitoring of polarization mode dispersion and chromatic
      dispersion.
AB  - We have developed new expressions for power fading and average power fading owing
      to polarization mode dispersion (PMD) and chromatic dispersion in terms of the
      angle of precession of the output state of polarization about the PMD vector.
      Based on these expressions, a simple and novel pilot-tone-based technique for
      simultaneous monitoring of chromatic dispersion and PMD is proposed. Experimental
      results demonstrate the effectiveness of the proposed technique; these results
      agree well with the theoretical analysis.

PMID- 16633432
TI  - Computationally efficient method for retrieving aerosol optical depth from ATSR-2
      and AATSR data.
AB  - We present a robust and computationally efficient method for retrieving aerosol
      optical depth (AOD) from top-of-atmosphere ATSR-2 (Along-Track Scanning
      Radiometer) and AATSR (Advanced ATSR) reflectance data that is formulated to
      allow retrieval of the AOD from the 11 year archive of (A)ATSR data on the global
      scale. The approach uses a physical model of light scattering that requires no a
      priori information on the land surface. Computational efficiency is achieved by
      using precalculated lookup tables (LUTs) for the numerical inversion of a
      radiative-transfer model of the atmosphere. Estimates of AOD retrieved by the LUT
      approach are tested on AATSR data for a range of global land surfaces and are
      shown to be highly correlated with sunphotometer measurements of the AOD at 550
      nm. (Pearson's correlation coefficient r(2) is 0.71.).

PMID- 16633433
TI  - Determination of cloud effective particle size from the multiple-scattering
      effect on lidar integration-method temperature measurements.
AB  - A method is presented that permits the determination of the cloud effective
      particle size from Raman- or Rayleigh-integration temperature measurements that
      exploits the dependence of the multiple-scattering contributions to the lidar
      signals from heights above the cloud on the particle size of the cloud.
      Independent temperature information is needed for the determination of size. By
      use of Raman-integration temperatures, the technique is applied to cirrus
      measurements. The magnitude of the multiple-scattering effect and the above-cloud
      lidar signal strength limit the method's range of applicability to cirrus optical
      depths from 0.1 to 0.5. Our work implies that records of stratosphere temperature
      obtained with lidar may be affected by multiple scattering in clouds up to
      heights of 30 km and beyond.

PMID- 16633434
TI  - High-luminosity multipass cell for infrared imaging spectroscopy.
AB  - An original imaging multipass cell for infrared spectroscopy has been designed
      and built. The cell design is aimed at overcoming intrinsic sensitivity
      limitations associated with the low specific spectral radiance power of blackbody
      sources. Owing to the implemented low f number, the detector collects a large
      amount of the energy emitted over a wide angle by a blackbody source. In
      addition, the adopted optical configuration allows maintenance of the same
      spatial distribution of the radiance pattern at the cell entrance and exit
      (imaging capability) within an aperture area of several square millimeters. This
      feature allows the use of uncollimated blackbody-type emitter arrays and infrared
      sensor arrays coupled with linear, spectrally variable filters, and performance
      of spectroscopic measurements of infrared absorption for low concentrated gases
      detection. In the present design the cell has an f number of about 2, and the
      optical path is ten times larger than the cell length.

PMID- 16633435
TI  - Radiative model of post-breakdown laser-induced plasma expanding into ambient
      gas.
AB  - The dynamics of the radiative plasma expansion into an ambient gas is considered.
      The model describes the evolution of the plasma emission spectrum and the
      dynamics of the resulting shock wave. The time frame for the applicability of the
      model is in the tens of nanoseconds after the laser pulse is terminated, until a
      few microseconds later when the plasma ceases to emit. It is assumed that local
      thermodynamic equilibrium is established and that the plume expands with
      spherical symmetry. The model outputs are spatial and temporal distributions of
      atoms, ions, and electron number densities, evolution of atom and ion line
      profiles, and the shock wave. The model should be applicable to spectroscopic
      analysis of the initial plasma state and plasma dynamics.

PMID- 16633436
TI  - Dispersion properties of x-ray waveguides.
AB  - We study the propagation of ultrashort pulses in x-ray waveguides (WGs) by
      addressing the problem of the temporal dispersion. Starting from basic equations,
      by means of numerical calculation we demonstrate that far from the absorption
      edges of the WGs the cladding's material dispersion is negligible. However, close
      to the absorption edge significant dispersion can take place. This behavior could
      in principle be exploited to manipulate incoming chirped beams. Moreover, using
      the two coherent beams produced by the WG in the second (and higher) order of
      resonance suggests the use of the WC as a dispersion-free beam splitter, which
      can facilitate x-ray pump-probe experiments in the femtosecond temporal range
      without the need for external sources.

PMID- 16633437
TI  - Dynamically adaptive mesh refinement technique for image reconstruction in
      optical tomography.
AB  - A novel adaptive mesh technique is introduced for problems of image
      reconstruction in luminescence optical tomography. A dynamical adaptation of the
      three-dimensional scheme based on the finite-volume formulation reduces
      computational time and balances the ill-posed nature of the inverse problem. The
      arbitrary shape of the bounding surface is handled by an additional refinement of
      computational cells on the boundary. Dynamical shrinking of the search volume is
      introduced to improve computational performance and accuracy while locating the
      luminescence target. Light propagation in the medium is modeled by the telegraph
      equation, and the image-reconstruction algorithm is derived from the Fredholm
      integral equation of the first kind. Stability and computational efficiency of
      the introduced method are demonstrated for image reconstruction of one and two
      spherical luminescent objects embedded within a breastlike tissue phantom.
      Experimental measurements are simulated by the solution of the forward problem on
      a grid of 5x5 light guides attached to the surface of the phantom.

PMID- 16633438
TI  - Model function to calculate the refractive index of native hemoglobin in the
      wavelength range of 250-1100 nm dependent on concentration.
AB  - The real part of the complex refractive index of oxygenated native hemoglobin
      solutions dependent on concentration was determined in the wavelength range 250
      to 1100 nm by Fresnel reflectance measurements. The hemoglobin solution was
      produced by physical hemolysis of human erythrocytes followed by
      ultracentrifugation and filtration. A model function is presented for calculating
      the refractive index of hemoglobin solutions depending on concentration in the
      wavelength range 250 to 1100 nm.

PMID- 16633440
TI  - Mental patients in prisons: punishment versus treatment?

PMID- 16633441
TI  - Mental health: scarce resources need new paradigms.
AB  - Mental disorders represent a major challenge to global development worldwide.
      Effective (and in some cases cost-effective) interventions are available for
      almost all of them. However, these interventions are often not implemented.
      Unknown variables, quite similar among themselves across the world, can have a
      strong influence in increasing the service quality in spite of the differences in
      resources and technologies. These unknown variables often result from the
      adoption of paradigms which are relatively independent from resources and
      technologies. We examine here four such paradigms.

PMID- 16633442
TI  - Functional neuroimaging in mental disorders.
AB  - Recent advances in functional neuroimaging allow us to map neural activity in the
      living human brain with precise spatial and temporal resolution and provide an
      unprecedented opportunity to examine the neurocognitive components of mental
      disorders. In this article we aim to summarize the main functional neuroimaging
      findings in the major psychiatric disorders and the different methodological
      approaches that have been used to study them. We will discuss studies of the
      resting state and of activation during the performance of cognitive tasks, and
      studies focused on specific psychiatric symptoms. We will also review work on
      functional connectivity, discuss future directions in the field and consider how
      functional neuroimaging may contribute to clinical practice.

PMID- 16633443
TI  - Body dysmorphic disorder: recognizing and treating imagined ugliness.
AB  - Body dysmorphic disorder (BDD), also known as dysmorphophobia, is a severe
      psychiatric disorder that occurs around the world. However, the diagnosis is
      usually missed in clinical settings. It is important to recognize and diagnose
      BDD, because this disorder is relatively common and causes significant distress
      and impairment in functioning. It is also associated with markedly poor quality
      of life. Although research on effective treatment is still limited, serotonin
      reuptake inhibitors (SRIs) are currently considered the medication treatment of
      choice. For symptoms to improve, a relatively high SRI dose and at least 12 weeks
      of treatment is often needed. The psychosocial treatment of choice is cognitive
      behavioral therapy, consisting of elements such as exposure, response prevention,
      behavioral experiments, and cognitive restructuring. Although knowledge of BDD is
      rapidly increasing, further research is needed on all aspects of this disorder,
      including treatment studies, epidemiology studies, and investigation of its cross
      cultural features and pathogenesis.

PMID- 16633444
TI  - Psychiatric comorbidity: is more less?
AB  - With each successive revision of the DSM and ICD, psychiatric comorbidity has
      become more prevalent. The 'atheoretical' approaches of the DSM and ICD
      explicitly encourage multiple diagnoses with few exclusionary hierarchies, in the
      hope that all clinically relevant information will be captured. However, the
      current strategy of diagnosing 'maximal' comorbidity may not reflect 'optimal'
      comorbidity. Many clinicians and health information systems, particularly those
      in developing countries, have a limited capacity for capturing this diagnostic
      information, and fail to characterize additional diagnoses that are present. This
      article will address the evolution of our current diagnostic system as a way of
      understanding the emergence of comorbid psychiatric diagnoses. Alternative
      diagnostic approaches (a dimensional system, diagnostic hierarchies, and mixed
      diagnostic categories) that could be used to address the emergence of comorbid
      psychiatric diagnoses are considered. Future challenges for the next evolution of
      DSM and ICD are presented.

PMID- 16633445
TI  - The syndrome--an antidote to spurious comorbidity?

PMID- 16633446
TI  - Disorders are different from diseases.

PMID- 16633447
TI  - State-of-the-art psychiatric diagnosis.

PMID- 16633448
TI  - Comorbidity and Chairman Mao.

PMID- 16633449
TI  - Different reasons for comorbidity require different solutions.

PMID- 16633450
TI  - Psychiatric comorbidity presents special challenges in developing countries.

PMID- 16633451
TI  - Comorbidity: the African perspective.

PMID- 16633452
TI  - The antisaccade task and neuropsychological tests of prefrontal cortical
      integrity in schizophrenia: empirical findings and interpretative considerations.
AB  - To date, every published study of the antisaccade task has replicated the finding
      that schizophrenia patients make an increased number of errors. This finding has
      been interpreted as support for frontal and/or basal ganglia dysfunction in
      schizophrenia, primarily because neurological patients with pathology in these
      brain regions also make large numbers of errors on the antisaccade task. Here, we
      compared the performance of schizophrenia patients and nonpsychiatric controls on
      an antisaccade task and on two neuropsychological tests, the Wisconsin Card
      Sorting Test, which is assumed to tap frontal lobe functioning, and the
      interference condition of the Stroop Test, which is thought to tap dorsolateral
      prefrontal cortex/anterior cingulate functioning. We examined the pattern of
      intercorrelations among these tasks. Schizophrenia patients made significantly
      more errors on the antisaccade task, made more perseverative errors and achieved
      fewer categories on the Wisconsin Card Sorting Test, and were significantly
      slower during the interference condition of the Stroop Test than were
      nonpsychiatric controls. Antisaccade errors were significantly correlated with
      interference performance on the Stroop in schizophrenia patients and in controls,
      but were not significantly correlated with the measures of Wisconsin Card Sorting
      Test performance in either group. The pattern of intercorrelation suggests that
      these tasks should not be thought of as representing a unitary variable of
      "frontal cortical integrity". Although aspects of these tasks tap the ability to
      inhibit prepotent responses, each task is also behaviorally complex. The
      multifaceted nature of these tasks makes it difficult to isolate which brain
      regions are part of the network underlying the specific act of inhibiting a
      prepotent response (for example, the reflexive saccade toward the novel
      peripheral target) and which regions participate in aspects of task performance
      that are related to non-inhibitory components (for example, executing an
      antisaccade). A broadly distributed network is undoubtedly involved in both
      processes. Parsing the various components of cognitively complex tasks may help
      to clarify both the specific behaviors that are anomalous and their underlying
      neural substrates. We also address the complexity of inferring localized brain
      dysfunction in schizophrenia patients based on seemingly analogous behavioral
      deficits in neurological populations.

PMID- 16633453
TI  - A cross-cultural study of eating attitudes in adolescent South African females.
AB  - Eating disorders were first described in black females in South Africa in 1995. A
      subsequent community based study of eating attitudes amongst adolescent females
      in an urban setting suggested that there would be increasing numbers of sufferers
      from within the black community. The current study sought to extend these
      findings using a larger, more representative urban sample. The results support
      those of the preliminary study. The underlying basis for the emerging phenomenon
      is discussed.

PMID- 16633454
TI  - Depression among older people in Europe: the EURODEP studies.
AB  - The data from nine centres in Europe which had used the Geriatric Mental Scale
      (GMS) AGECAT were analysed to compare prevalence of diagnoses in subjects aged 65
      years and over living in the community. Levels of depressive illness were:
      Iceland 8.8%, Liverpool 10.0%; Zaragoza 10.7%; Dublin 11.9%; Amsterdam 12.0%;
      Berlin 16.5%; London 17.3%; Verona 18.3% and Munich 23.6%. Taking all levels of
      depression, five high (Amsterdam, Berlin, Munich, London and Verona) and four low
      (Dublin, Iceland, Liverpool, Zaragoza) scoring centres were identified. Meta
      analysis of all 13,808 subjects yielded a mean level of depression of 12.3% (95%
      CI 11.8-12.9), 14.1% for women (95% CI 13.5-14.8) and 8.6% for men (95% CI 7.9
      9.3). Symptom levels varied between centres: 40% of the total study population in
      Amsterdam reported depressive mood against only 26% in Zaragoza. To incorporate
      studies from other centres using other methods for depression identification, the
      EURO-D scale was developed from 12 items of the GMS and validated against other
      scales and expert diagnosis. A two factor solution emerged, an 'affective
      suffering factor' and a 'motivation factor'. The EURO-D scale was applied to 14
      population based surveys. Depression score tended to increase with age unlike
      levels of prevalence of depression. Large between centre differences were evident
      in levels of depression unexplained by age, gender or marital status. These data
      show that depressive illness defined as suitable for intervention is common among
      older people in Europe. Opportunities for effective treatment are almost
      certainly being lost. Levels of depressive symptoms vary significantly between
      high and low scoring centres, prompting the next phase of this study, an
      examination of risk factors in Europe.

PMID- 16633455
TI  - Traumatic grief in Kenyan bereaved parents following the Kyanguli School fire
      tragedy.
AB  - Following the death of 67 boys in a fire tragedy at Kyanguli School in rural
      Kenya, the level of traumatic grief was assessed in a sample of 164 parents and
      guardians whose sons died in the fire. The study was cross-sectional. Counseling
      services were offered to all the bereaved parents soon after the tragedy. The
      subjects were interviewed using the Traumatic Grief Scale. A group of 92
      parents/guardians was interviewed 2 months after the event, while the other group
      of 72 was assessed 7 days later. The second group of bereaved parents also
      completed the Self Rating Questionnaire (SRQ) and the Ndetei-Othieno-Kathuku
      scale (NOK). Over 90% of parents from both groups had a yearning for the departed
      and found themselves searching for him quite often. There was no much difference
      in terms of symptoms profile or intensity between the two groups. It appears that
      the counseling offered had minimal impact on the levels of distress.

PMID- 16633456
TI  - The World Federation for Mental Health: its origins and contemporary relevance to
      WHO and WPA policies.
AB  - The World Federation for Mental Health (WFMH) is an international, multi
      professional non-governmental organization (NGO), including citizen volunteers
      and former patients. It was founded in 1948 in the same era as the United Nations
      (UN) and the World Health Organization (WHO). For many years, led mainly by
      psychiatrists focused on social, peace-related and human rights issues, it was
      the only international mental health NGO consulting with UN agencies. Since the
      late 1990s, as a global alliance of national mental health associations focused
      mainly on traditional mental health issues and on prevention and promotion, it
      has continued its long-time collaboration with WHO. Its policy concerns and those
      of international professional associations such as the WPA could be mutually
      advanced through partnerships aimed at achieving common goals.

PMID- 16633457
TI  - The practice research network: benefits and limitations.
AB  - The 5-year experience of the Canadian Psychiatric Association's practice research
      network (PRN) in providing a window on physician practices in typical clinical
      settings is reviewed. The strengths of the PRN reside in the active participation
      of clinicians in self-monitoring as well as in the instrument adaptability and
      flexibility in addressing current issues of national relevance, including
      identification of educational needs. The PRN limitations are in the fact that the
      responders in general have limited research experience and the instrument can
      provide broad-based answers only. The creation of a national PRN is however an
      effective strategy in narrowing the gap between practice and research.

PMID- 16633458
TI  - Women's mental health in Pakistan.
AB  - In Pakistan, societal attitudes and norms, as well as cultural practices (Karo
      Kari, exchange marriages, dowry, etc.), play a vital role in women's mental
      health. The religious and ethnic conflicts, along with the dehumanizing attitudes
      towards women, the extended family system, role of in-laws in daily lives of
      women, represent major issues and stressors. Such practices in Pakistan have
      created the extreme marginalisation of women in numerous spheres of life, which
      has had an adverse psychological impact. Violence against women has become one of
      the acceptable means whereby men exercise their culturally constructed right to
      control women. Still, compared to other South Asian countries, Pakistani women
      are relatively better off than their counterparts.

PMID- 16633459
TI  - '5000 Years of Science and Care--Building the Future of Psychiatry': the 13th
      World Congress of Psychiatry.

PMID- 16633460
TI  - Research for Change: the role of scientific journals publishing mental health
      research.
AB  - There is an enormous gap between the burden of mental disorders and mental health
      resources in low- and middle-income countries. The Mental Health: Global Action
      Programme of the World Health Organization (WHO) envisions an active role for
      research in the multidimensional efforts required to change the current mental
      health situation in these countries (Research for Change). WHO's strategies to
      achieve this include developing a research policy and a priority agenda at
      country level with active collaboration from all stakeholders, building research
      capacity and infrastructure and involving scientific journals to stimulate and
      disseminate public health oriented research. A recently agreed joint statement by
      editors of prominent journals publishing mental health research and WHO sets
      major objectives and some possible strategies for achieving this. WHO is
      committed to making Research for Change a reality by working with partners who
      share this aim.

PMID- 16633461
TI  - Gene-environment interactions in mental disorders.
AB  - Research clearly shows that both nature and nurture play important roles in the
      genesis of psychopathology. In this paper, we focus on 'gene-environment
      interaction' in mental disorders, using genetic control of sensitivity to the
      environment as our definition of that term. We begin with an examination of
      methodological issues involving gene-environment interactions, with examples
      concerning psychiatric and neurological conditions. Then we review the
      interactions in psychiatric disorders using twin, adoption and association
      designs. Finally, we consider gene-environment interactions in selected
      neurodevelopmental disorders (autism and schizophrenia).

PMID- 16633462
TI  - Pharmacotherapy in the treatment of Alzheimer's disease: an update.
AB  - This review summarises the pharmacological properties of the main classes of
      drugs in current use for the symptomatic treatment of Alzheimer's disease. These
      may be divided into two major groups: those enhancing cholinergic function which
      has been shown to be defective in the disease, and those which either directly or
      indirectly reduce free radical/inflammatory processes in the brain. To date, none
      of the drugs available has been shown to reverse the pathological changes
      associated with the disease. However, a number of drugs are in development which
      are designed to block the neurotoxic action of amyloid beta peptide and thereby
      reverse the underlying pathological processes. These include the gamma secretase
      inhibitors and vaccines against amyloid beta peptide. The limitations of these
      novel approaches are discussed.

PMID- 16633463
TI  - Diagnosis and management of post-partum disorders: a review.
AB  - This paper reviews the psychiatry of the puerperium, in the light of work
      published during the last eight years. Many distinct disorders are seen. In
      addition to various psychoses and a heterogeneous group of depressions, there are
      specific anxiety, obsessional and stress-related disorders. It is important to
      identify severe disorders of the mother-infant relationship, which usually
      respond to treatment, but have pernicious effects if untreated. The complexity of
      post-partum psychiatry requires the deployment of multidisciplinary specialist
      teams, which can handle the challenges of therapy, prevention, training, research
      and service development.

PMID- 16633464
TI  - Postnatal mental disorder: towards ICD-11.

PMID- 16633465
TI  - An evidence-based approach to post-partum depression.

PMID- 16633466
TI  - Childbirth is not only complex: it may also be dangerous.

PMID- 16633467
TI  - Post-partum psychiatric care in India: the need for integration and innovation.

PMID- 16633468
TI  - Postnatal depression, social support, and child abuse.

PMID- 16633469
TI  - The challenges of motherhood and mental health.

PMID- 16633470
TI  - Mother-infant bonding disorders and use of Parental Bonding Questionnaire in
      clinical practice.

PMID- 16633471
TI  - Implementation of evidence-based treatment for schizophrenic disorders: two-year
      outcome of an international field trial of optimal treatment.
AB  - According to clinical trials literature, every person with a schizophrenic
      disorder should be provided with the combination of optimal dose antipsychotics,
      strategies to educate himself and his carers to cope more efficiently with
      environmental stresses, cognitive-behavioural strategies to enhance work and
      social goals and reducing residual symptoms, and assertive home-based management
      to help prevent and resolve major social needs and crises, including recurrent
      episodes of symptoms. Despite strong scientific support for the routine
      implementation of these 'evidence-based' strategies, few services provide more
      than the pharmacotherapy component, and even this is seldom applied in the manner
      associated with the best results in the clinical trials. An international
      collaborative group, the Optimal Treatment Project (OTP), has been developed to
      promote the routine use of evidence-based strategies for schizophrenic disorders.
      A field trial was started to evaluate the benefits and costs of applying evidence
      based strategies over a 5-year period. Centres have been set up in 18 countries.
      This paper summarises the outcome after 24 months of 'optimal' treatment in 603
      cases who had reached this stage in their treatment by the end of 2002. On all
      measures the evidence-based OTP approach achieved more than double the benefits
      associated with current best practices. One half of recent cases had achieved
      full recovery from clinical and social morbidity. These advantages were even more
      striking in centres where a random-control design was used.

PMID- 16633472
TI  - Mental disorders among the Borana semi-nomadic community in Southern Ethiopia.
AB  - This study aimed to estimate the lifetime prevalence and socio-demographic
      correlates of psychiatric disorders among the Borana semi-nomadic community of
      the Oromia region of Ethiopia. 1854 people of both sexes, aged 15 years and
      above, were interviewed during the survey. The households were selected by using
      a cluster sampling method proportionate to population size. The interviews were
      conducted by trained high school graduates using the Oromiffa version of the
      Composite International Diagnostic Interview (CIDI). The lifetime prevalence of
      ICD-10 mental disorders, including substance abuse, was 21.6%. Affective
      disorders were found in 1.7% of the study population, whereas neurotic and
      somatoform disorders constituted 14%. No cases of schizophrenia were detected.
      The prevalence of substance use was 10.1%. Studies using other methods, including
      interview by clinicians, might shed more light on the nature of mental illness in
      this unique community.

PMID- 16633473
TI  - The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC).
      Development, reliability and validity.
AB  - The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC) is a
      computerised clinical assessment tool developed to assess and identify a wide
      range of mental health problems in primary care. It generates a computer
      diagnosis, a symptom rating, a self-harm risk assessment, and a referral letter.
      Patients from primary care and community psychiatric outpatient clinics and a
      small sample of inpatients were interviewed for a period of two months using the
      GMHAT/PC. A proportion of patients were simultaneously rated by a psychiatrist
      and a general practitioner for inter-rater reliability. All patients also
      completed the Hospital Anxiety and Depression Scale (HAD). To conduct the
      interview was easy in all settings and took 10-15 minutes for patients who had
      psychiatric symptoms. Inter-rater agreement on mental state symptom groups ranged
      from 0.49 to 1 (kappa). The computer diagnosis correlated highly with the
      clinical diagnosis and there was a good level of agreement between HAD ratings
      and GMHAT/PC ratings. These data suggest that the GMHAT/PC is an easy to
      administer computerised tool which can be used in primary care for the
      standardised assessment of mental health problems.

PMID- 16633474
TI  - Mental health epidemiological research in South America: recent findings.
AB  - This paper aims to review the recent mental health epidemiological research
      conducted in South America. The Latin American and the Caribbean (LILACS)
      database was searched from 1999 to 2003 using a specific strategy for
      identification of cohort, case-control and cross-sectional population-based
      studies in South America. The authors screened references and identified relevant
      studies. Further studies were obtained contacting local experts in epidemiology.
      140 references were identified, and 12 studies were selected. Most selected
      studies explored the prevalence and risk factors for common mental disorders, and
      several of them used sophisticated methods of sample selection and analysis.
      There is a need for improving the quality of psychiatric journals in Latin
      America, and for increasing the distribution and access to research data.
      Regionally relevant problems such as violence and substance abuse should be
      considered in designing future investigations in this area.

PMID- 16633475
TI  - On the China issue.

PMID- 16633476
TI  - What can philosophy do for psychiatry?
AB  - This article illustrates the practical impact of recent developments in the
      philosophy of psychiatry in five key areas: patient-centred practice, new models
      of service delivery, neuroscience research, psychiatric education, and the
      organisation of psychiatry as an international science-led discipline focused on
      patient care. We conclude with a note on the role of philosophy in countering the
      stigmatisation of mental disorder.

PMID- 16633477
TI  - Interpersonal psychotherapy: principles and applications.
AB  - This article briefly describes the fundamental principles and some of the
      clinical applications of interpersonal psychotherapy (IPT), a time-limited,
      empirically validated treatment for mood disorders. IPT has been tested with
      general success in a series of clinical trials for mood and, increasingly, non
      mood disorders; as both an acute and maintenance treatment; and in differing
      treatment formats. As a result of this research success, IPT is spreading from
      research trials to clinical practice in various countries around the world.

PMID- 16633478
TI  - Soteria Berne: an innovative milieu therapeutic approach to acute schizophrenia
      based on the concept of affect-logic.
AB  - The name "Soteria" stands for an alternative low-drug milieu-therapeutic approach
      to acute schizophrenia that was first implemented by Mosher and Menn in San
      Francisco, and since 1984 further developed by Ciompi and co-workers in Berne, on
      the basis of their concept of affect-logic, that emphasizes the often neglected
      influence of emotional factors in schizophrenia. In both settings, equal and even
      partly better therapeutic results, compared with traditional methods, were
      obtained with much lower doses of antipsychotics and comparable daily costs.
      Basic concepts, practical proceedings and empirical findings of Soteria Berne are
      reported, and their theoretical and practical implications for mainstream
      psychiatry are discussed. They support the hypothesis of a crucial pathogenetic
      and therapeutic-preventive role played by emotional factors not only in the so
      called affective psychoses, but also in schizophrenia.

PMID- 16633479
TI  - Suicide prevention: at what level does it work?
AB  - This paper reviews the prevention of suicide according to programme evaluation,
      risk and protective factors, type of intervention, level of intervention and the
      interface between clinical and public health levels. From nearly a century of
      experience, a few but important lessons have been learned: since suicide is
      affected by sociocultural factors, there is no safe indication that what has
      worked somewhere will work elsewhere; in order to acquire any public health
      importance, suicide prevention programmes must clearly spell out their objectives
      and targets; isolated actions have a much lesser probability of yielding
      significant population outcome results than more articulated approaches that
      integrate public health measures and individual care with appropriate follow-up
      and social support.

PMID- 16633480
TI  - Preventing suicide: a call to action.

PMID- 16633481
TI  - Evaluating suicide prevention: various approaches needed.

PMID- 16633482
TI  - Suicide prevention is far more than a psychiatric business.

PMID- 16633483
TI  - Suicide prevention in developing countries: where should we start?

PMID- 16633484
TI  - Brazil: the need for violence (including suicide) prevention.

PMID- 16633485
TI  - Suicide prevention: the urgent need in developing countries.

PMID- 16633486
TI  - Looking back and ahead. Suicidology and suicide prevention: do we have
      perspectives?

PMID- 16633487
TI  - Suicidal behaviour: comments, advancements, challenges. A European perspective.

PMID- 16633488
TI  - Premorbid characterization in schizophrenia: the Pittsburgh High Risk Study.
AB  - Prospective studies of young relatives at risk for schizophrenia can shed light
      on the possible premorbid precursors of the disease. Ongoing studies in
      Pittsburgh suggest that young non-psychotic high risk relatives have
      neurobehavioral, brain structural, physiological, and neurochemical deficits that
      may date back to childhood or earlier. We summarize these data, review the
      relevant literature in this emerging field, and provide some new data suggesting
      alterations in sleep architecture in young relatives at risk for schizophrenia.
      Collectively, such data are likely to help us to predict the eventual emergence
      of schizophrenia, schizophrenia spectrum or non-spectrum psychopathology.

PMID- 16633489
TI  - Application of the Eating Attitudes Test (EAT-26) in a rural, Zulu speaking,
      adolescent population in South Africa.
AB  - This study was undertaken as part of an exploration of the potential risk for
      future eating disorders in the black female population of South Africa. Previous
      research has documented eating attitudes suggesting that such a risk exists in
      urban populations. A translated version of the Eating Attitudes Test (EAT-26) was
      applied in a Zulu speaking, rural population (n=361). A prevalence of 3% for
      abnormal eating attitudes was established. In keeping with the hypothesis, the
      findings suggest that the risk for developing an eating disorder in a rural
      population is somewhat lower. In this regard, there does appear to be an urban
      rural divide, which may have implications for the prevention of the emergence of
      eating disorders in black, South African adolescents. However, the validity of
      the EAT-26 in this population is a consideration in interpreting the data.

PMID- 16633490
TI  - Developing a New Zealand casemix classification for mental health services.
AB  - This study aimed to develop a casemix classification of characteristics of New
      Zealand mental health services users. Over a six month period, patient
      information, staff time and service costs were collected from 8 district health
      boards. This information was analysed seeking the classification of service user
      characteristics which best predicted the cost drivers of the services provided. A
      classification emerged which explained more than two thirds of the variance in
      service user costs. It can be used to inform service management and funding, but
      it is premature to have it determine funding.

PMID- 16633491
TI  - Hidden science? A glimpse at some work in Africa.
AB  - Even though Africa contributes a disproportionately small quantity to the world
      scientific information pool, much of what it produces may be unavailable to the
      scientific community. A number of scientific journals published on the continent
      but not listed in international indexes often report studies in mental health and
      related fields. An analysis of some of these publications revealed that, over the
      period 1999-2003, research issues addressed include substance abuse, neuroscience
      and neuropsychiatry, health services, and child mental health. Most of the
      studies are descriptive and based on convenient or clinical samples. Community
      based epidemiological studies and those examining the cost-effectiveness of
      different forms of intervention are rare. Even though the strength of the studies
      reported varied considerably, they nevertheless suggest that a considerable
      amount of research activities is taking place on the continent. The number and
      types of studies reported highlight the poor investment in research in Africa.

PMID- 16633492
TI  - Concurrent substance-related disorders and mental illness: the North American
      experience.
AB  - Ingredients of the evolving North American experience in addressing the
      management of patients with concurrent substance-related disorders and mental
      illness are presented. This experience as well as select data from Europe and
      Australia indicate a growing empirically-based consensus to provide an integrated
      approach to the care of these patients. It also highlights the necessity to
      conduct local surveys of needs and resources and adapt the published clinical
      experience to the local system of care, resources and culture.

PMID- 16633493
TI  - Globalization and mental health: a WPA perspective.

PMID- 16633494
TI  - Are genes destiny? Have adenine, cytosine, guanine and thymine replaced Lachesis,
      Clotho and Atropos as the weavers of our fate?
AB  - It is as futile to ask how much of the phenotype of an organism is due to nature
      and how much to its nurture as it is to determine how much of the area of a
      rectangle is due to its length and how much to its height. Phenotype and area are
      joint products. The spectacular success of genomics, unfortunately, threatens to
      re-awaken belief in genes as the principal determinants of human behavior. This
      paper develops the thesis that gene expression is modified by environmental
      inputs and that the impact of the environment on a given organism is modified by
      its genome. Genes set the boundaries of the possible; environments parse out the
      actual.

PMID- 16633495
TI  - Menstrual psychosis.
AB  - This paper reviews the literature on menstrual psychosis and proposes a new
      classification, adapting that of v. Krafft-Ebing (1902) and Jolly (1914). The
      world literature consists mainly of case reports; they include a few with data
      good enough for a statistical demonstration of the link between onset and menses.
      These well-documented cases include examples of pre-menstrual, catamenial,
      paramenstrual and mid-cycle onsets, and continuous illnesses with phasic shifts
      rhythmic with the menstrual cycle. In sufferers, episodes seem to be concentrated
      around the menarche and after childbirth. The clinical picture resembles that of
      puerperal psychosis, and there are at least 20 women who have suffered both
      psychoses at different epochs in their lives. Both seem to fall within the manic
      depressive rubric, so that menstruation can be another trigger of a bipolar
      episode. Some work suggests an association with anovulatory cycles. Cases
      starting before the menarche suggest a diencephalic origin.

PMID- 16633496
TI  - Migration, cultural bereavement and cultural identity.
AB  - Migration has contributed to the richness in diversity of cultures, ethnicities
      and races in developed countries. Individuals who migrate experience multiple
      stresses that can impact their mental well being, including the loss of cultural
      norms, religious customs, and social support systems, adjustment to a new culture
      and changes in identity and concept of self. Indeed, the rates of mental illness
      are increased in some migrant groups. Mental health practitioners need to be
      attuned to the unique stresses and cultural aspects that affect immigrants and
      refugees in order to best address the needs of this increasing and vulnerable
      population. This paper will review the concepts of migration, cultural
      bereavement and cultural identity, and explore the interrelationship between
      these three aspects of the migrant's experience and cultural congruity. The
      complex interplay of the migration process, cultural bereavement, cultural
      identity, and cultural congruity, along with biological, psychological and social
      factors, is hypothesized as playing a major role in the increased rates of mental
      illness in affected migrant groups.

PMID- 16633497
TI  - Prevention of substance abuse: a brief overview.
AB  - Recent advances in psychosocial research and neurosciences have provided new
      avenues for prevention of substance abuse at the individual and community level.
      A series of risk and protective factors affecting the likelihood of using and
      abusing substances have been identified. The scope of prevention has been
      broadened, allowing the prescription of different interventions for individuals
      according to their varying degrees of vulnerability to substance experimentation,
      continuous use and dependence. An increased awareness of comorbidity between
      mental and substance use disorders provides an arena for prevention within
      psychiatry and related disciplines. Emphasis on program evaluation has helped
      identify cost effective programs and policies. The integration of prevention
      within healthy life style policies and programs, including interventions at the
      school, family and community levels, is more likely to produce the desired
      outcomes.

PMID- 16633498
TI  - The role of psychiatrists in prevention of psychoactive substance use and
      dependence: beyond clinical practice.

PMID- 16633499
TI  - Substance abuse prevention: practical strategies for psychiatrists in the 21st
      century.

PMID- 16633500
TI  - How effective is substance abuse prevention?

PMID- 16633501
TI  - Substance abuse intervention in South Africa.

PMID- 16633502
TI  - Don't drink and drive: the successful message of Mothers Against Drunk Driving
      (MADD).

PMID- 16633503
TI  - Prevention of substance abuse: the Indian experience.

PMID- 16633504
TI  - Choosing cost-effective interventions in psychiatry: results from the CHOICE
      programme of the World Health Organization.
AB  - There is increasing recognition at both the international and national level of
      the disease burden attributed to psychiatric disorders, yet little is known about
      how much of this burden is or could be averted by current or scaled-up
      implementation of effective interventions. In addition, little is known about the
      costs and cost-effectiveness of such interventions in most regions of the world,
      even though such information is of direct relevance to increased investment and
      service development. This research report provides an overview of the mental
      health component of the World Health Organization's CHOICE project, the aim of
      which is to generate cost-effectiveness evidence for a large number of
      interventions for leading contributors to disease burden in a range of
      geographical and epidemiological settings around the world. To date, expected
      costs (expressed in international dollars) and effects (measured in terms of
      disability adjusted life years, DALYs) of key pharmacological and psychosocial
      interventions have been modelled for schizophrenia, bipolar disorder, depression
      and panic disorder. The results of this analysis indicate that the most efficient
      interventions for common mental disorders (depression and panic disorder) can be
      considered very cost-effective (each DALY averted costs less than one year of
      average per capita income), while community-based interventions for more severe
      mental disorders using older antipsychotic and mood stabilising drugs meet the
      criterion for being cost-effective (each DALY averted costs less than three times
      the average annual income). These findings provide relevant new information to
      health policy makers regarding the relative value of investing in psychiatric
      care, and in so doing may help to remove one of many remaining barriers to a more
      appropriate public health response to the burden of these conditions.

PMID- 16633505
TI  - Effectiveness of a psychoeducational intervention for families of patients with
      schizophrenia: preliminary results of a study funded by the European Commission.
AB  - In spite of their proven efficacy, psychoeducational interventions for families
      of patients with schizophrenia are not being commonly applied in clinical
      practice. In this report, we present the preliminary results of a one-year follow
      up study on the implementation and effectiveness of a psychoeducational family
      intervention in six European countries. Forty-eight professionals were involved
      in the study and provided the intervention for one year to 55 families of
      patients with schizophrenia. During the implementation period, the professionals
      reported significant organisational difficulties in the provision of the
      intervention, but acknowledged an improvement of their relationships with users
      and their families. At follow-up assessment, statistically significant
      improvements were found in patients' symptoms and social functioning as well as
      in relatives' burden, coping strategies and social resources.

PMID- 16633506
TI  - Psychological effects of the Nairobi US embassy bomb blast on pregnant women and
      their children.
AB  - A descriptive study was carried out in pregnant women who were affected by the
      1998 bomb blast in Nairobi, Kenya, and their babies who were in utero at the time
      of the blast. The psychological effects of the event on the exposed women were
      severe. After three years, the average score on the Impact of Event Scale -
      Revised was still higher than 29 for the three subscales combined, suggesting
      that most of the study group was still suffering from clinical post-traumatic
      stress disorder (PTSD). The scores on all Childhood Personality Scale (CPS)
      subscales were significantly higher in children of the study group than in
      controls. The mothers' PTSD symptom levels at one month after the blast
      correlated with the children's CPS profiles.

PMID- 16633507
TI  - Working life and mental health - A challenge to psychiatry?
AB  - According to the World Health Organization, "mental health problems and stress
      related disorders are the biggest overall cause of early death in Europe". Some
      of the root causes of this morbidity and mortality are related to living and
      working conditions that are accessible to preventive and therapeutic
      interventions, individual as well as collective ones. A political mandate for
      such interventions is now developing. Members of the WPA Section on Occupational
      Psychiatry have contributed to this development and we now invite the readers to
      join the Section in its endeavours.

PMID- 16633508
TI  - The WPA tsunami programme.

PMID- 16633509
TI  - The WHO's mental health response to the Asian tsunami.

PMID- 16633510
TI  - The mental health challenge in Sri Lanka from working within the disaster area.

PMID- 16633511
TI  - The multimodal treatment of eating disorders.
AB  - The treatment of eating disorders is based on a multimodal model, recognizing
      that these disorders do not have a single cause or a predictable course. The
      treatment strategy is determined by the severity of illness and the specific
      eating disorder diagnosis. For the treatment of anorexia nervosa, the key
      elements are medical management, behavioral therapy, cognitive therapy and family
      therapy, while pharmacotherapy is at best an adjunct to other therapies. In
      bulimia nervosa, the treatment of choice is cognitive-behavioral therapy, but a
      greater improvement in mood and anxiety occurs when antidepressant therapy is
      added. In binge eating disorder, cognitive-behavioral therapy and interpersonal
      therapy produce substantial and long-lasting changes and pharmacological
      treatment has often a useful role.

PMID- 16633512
TI  - Constructivism and psychotherapy.
AB  - Constructivism is a metatheoretical perspective that embraces diverse traditions
      in medicine, philosophy, psychology, and spiritual wisdom. Constructive
      psychotherapy emphasizes complex cycles in the natural ordering and reorganizing
      processes that characterize all development in living systems. Individuals are
      encouraged to view themselves as active participants in their lives. Within rich
      contexts of human relationship and symbol systems, people make new meanings as
      they develop. Techniques from many different traditions can help people find and
      refine their sense of balance as they develop.

PMID- 16633513
TI  - Looking with both eyes open: fact and value in psychiatric diagnosis?
AB  - IN THIS ARTICLE WE ARGUE THE CASE FOR A PROPOSAL: that psychiatry should
      recognise, embrace and take seriously the role of values, alongside facts, in
      diagnosis. We present a three-step argument in support of our proposal; we raise
      a number of key questions from the perspectives of different stakeholders in
      mental health; and we conclude with a note on the significance of our proposal
      for building a more equal relationship between patients and professionals.

PMID- 16633514
TI  - Keeping an eye on clinical utility.

PMID- 16633515
TI  - Bug-eyed and breathless: emerging crises involving values.

PMID- 16633516
TI  - On winking at the facts, and losing one's Hare: value pluralism and the harmful
      dysfunction analysis.

PMID- 16633518
TI  - Recognizing that values matter.

PMID- 16633517
TI  - Recipe for disaster: professional and patient equally sharing responsibility for
      developing psychiatric diagnosis.

PMID- 16633519
TI  - Eyes and ears wide open: values in the clinical setting.

PMID- 16633520
TI  - Values and comprehensive diagnosis.

PMID- 16633521
TI  - Bridging the gap between fact and values.

PMID- 16633522
TI  - Looking with both the eyes and heart open: the meaning of life in psychiatric
      diagnosis.

PMID- 16633523
TI  - The need for trained eyes to see facts and values in psychiatric diagnosis.

PMID- 16633524
TI  - Coloring our eyes.

PMID- 16633525
TI  - Demoralization, anhedonia and grief in patients with severe physical illness.
AB  - Within the physically ill population, demoralization has been a valuable concept
      with which to consider dysphoric states. Moreover, it can be distinguished from
      other mood states. In this study we replicate previous research and show that
      demoralization can be distinguished from anhedonic depression and grief. All
      three correlate more or less equally with measures of depression (e.g., the Beck
      Depression Inventory), although they are differentiated on styles of coping, and
      social, family and physical functioning. These results confirm that
      distinguishing depression with demoralization from depression with anhedonia is
      both useful and scientifically valid. It sharpens the characterisation of
      dysphoric states and provides an empirical framework to enhance research into the
      aetiology and treatment of depression.

PMID- 16633526
TI  - Stigmatization of people with mental illnesses: a follow-up study within the
      Changing Minds campaign of the Royal College of Psychiatrists.
AB  - A population survey before the start of the Changing Minds campaign showed that
      negative opinions about people with mental illnesses were widely held, and that
      opinions about different disorders differed in important ways. We repeated the
      survey 5 years later, when the campaign had ended. Interviews were again
      conducted with a representative population sample (1725 interviews; response rate
      65%), enquiring about demographic variables, about eight opinions concerning
      seven common mental disorders, and whether the respondents knew anyone with one
      of these mental disorders. The pattern of response in this second survey
      resembled that in the first. However, there were significant changes. Though
      often small, apart from reported opinions concerning treatment and outcome, they
      were all reductions in the percentages of stigmatizing opinions. Seventy seven
      percent of respondents reported knowing someone with one of the seven disorders.
      Those who did so in respect of severe depression or panic and phobias were less
      likely to have stigmatizing opinions about people with the corresponding
      disorder, but the same did not apply to the other disorders. The greatest
      proportion of negative opinions was in the 16-19 year age group, and respondents
      with higher education were less likely than the rest to express such views. We
      conclude that stigmatizing opinions are frequent in the community but the various
      disorders are not stigmatized in the same way. Campaigns to reduce stigma should
      take account of these differences, and of the need to address young people.

PMID- 16633527
TI  - Global suicide rates among young people aged 15-19.
AB  - Global suicide rates among adolescents in the 15-19 age group, according to the
      latest World Health Organization (WHO) Mortality Database, were examined. Data
      for this age group were available from 90 countries (in some cases areas) out of
      the 130 WHO member states. The mean suicide rate for this age group, based on
      data available for the latest year, was 7.4/100,000. Suicide rates were higher in
      males (10.5) than in females (4.1). This applies in almost all countries. The
      exceptions are China, Cuba, Ecuador, El Salvador and Sri Lanka, where the female
      suicide rate was higher than the male. In the 90 countries (areas) studied,
      suicide was the fourth leading cause of death among young males and the third for
      young females. Of the 132,423 deaths of young people in the 90 countries, suicide
      accounted for 9.1%. The trend of suicide rates from 26 countries (areas) with
      data available during the period 1965-1999 was also studied. A rising trend of
      suicide in young males was observed. This was particularly marked in the years
      before 1980 and in countries outside Europe. The WHO database is the largest of
      its kind and, indeed, the only information source that can currently be used for
      analysis of global mortality due to suicide. Methodological limitations are
      discussed.

PMID- 16633529
TI  - A new beginning.

PMID- 16633528
TI  - Post-traumatic stress disorder in children.
AB  - In the past ten years, there has been increasing recognition that children who
      have been exposed to traumatic events can, like traumaexposed adults, develop
      post-traumatic stress disorder (PTSD). Practitioners therefore need to be able to
      recognise and treat post-traumatic stress reactions in children. However, the
      direct application of adult diagnostic criteria for PTSD can result in the
      misdiagnosis of post-traumatic stress reactions in children, while research has
      only recently begun to investigate the effectiveness of different treatments for
      children with PTSD. This article discusses issues regarding the assessment and
      diagnosis of post-traumatic stress reactions in children at different
      developmental stages, considers neurobiological, cognitive and other factors that
      are theorized to increase the risk of PTSD in trauma-exposed children, and
      evaluates current psychotherapeutic and pharmacotherapeutic treatments for
      childhood PTSD. The need for more systematic research on the management of PTSD
      in children is noted.

PMID- 16633530
TI  - The art of psychiatry.
AB  - Psychiatrists would undoubtedly support the notion of promoting such qualities as
      empathy, sensitivity and caring in the pursuit of good clinical practice.
      However, cultivating what we may call the "art of psychiatry" is not
      straightforward, since the qualities that constitute it are elusive. I propose
      that the means by which we can accomplish the goal of relating empathically and
      compassionately to our patients and their families is by regarding the humanities
      and the sciences as of equal relevance and as complementary. The humanities,
      particularly literature, the visual arts, film and music, are most suited to
      promoting empathic skills when they are woven into the clinical scenario.
      Examples are provided to demonstrate how this may be achieved. Were we to succeed
      in highlighting the art of psychiatry in our educational programs, and as part of
      continuing professional development, I surmise that our patients and their
      families would be the beneficiaries. We cannot merely vow to act empathically and
      sensitively. Instead, we should embark on a lifelong journey through the
      wonderful world of literature, the visual arts, film and music. The experience
      will not only prove appealing and engaging, but it will also go far to enrich our
      personal and professional lives.

PMID- 16633531
TI  - What can mental health interventions contribute to the global struggle against
      HIV/AIDS?
AB  - Mental health is an essential component of worldwide efforts to contain the
      spread of HIV infection and to treat those who are already infected or affected
      by the virus. This paper describes the integration of mental health approaches
      into primary and secondary prevention strategies for vulnerable populations, the
      identification and management of psychiatric conditions that increase the risk
      for becoming infected with HIV, and the diagnosis and treatment of the
      neuropsychiatric manifestations of HIV infection.

PMID- 16633532
TI  - The Maudsley family-based treatment for adolescent anorexia nervosa.
AB  - Anorexia nervosa (AN) usually onsets in mid-adolescence and presents with serious
      psychiatric and medical morbidities. Yet, few psychological treatments for this
      debilitating disorder have been studied. One intervention which involves the
      parents of the adolescent has proved to be promising, especially in patients with
      a short duration of illness, i.e., less than three years. The benefits of this
      family-based treatment have also been shown to be enduring at five-year follow
      up. All available studies of psychological treatments for adolescent AN, both
      controlled trials and case series, are reviewed here. Almost all of them involve
      parents in treatment. These studies show that the majority of patients, even
      those who are severely ill, can be treated quite successfully as outpatients
      provided that the parents participate in treatment. In this family-based
      treatment, parents are viewed as a resource rather than a hindrance. Optimism
      regarding these encouraging findings should be tempered until larger scale
      randomized trials have been conducted.

PMID- 16633533
TI  - Mental health care for children and adolescents worldwide: a review.
AB  - The magnitude of mental health problems in children and adolescents has not been
      recognized sufficiently by many governments and decision-makers. This paper
      reviews the epidemiology of these problems as a basis for planning of services;
      the situation of mental health services for children and adolescents in the
      various regions of the world; the principles and strategies of intervention for
      mental health disorders in children and adolescents; and the role of
      international organizations and advocacy groups. It is concluded that old myths,
      treatments and policies are no longer to be tolerated and that there is now the
      opportunity to develop and implement evidence-based interventions, modern
      training programs and effective policies.

PMID- 16633534
TI  - Some reflections on the development of child and adolescent psychiatry.

PMID- 16633535
TI  - Improving mental health care for children and adolescents: a role for prevention
      science.

PMID- 16633536
TI  - Developing modern child psychiatry.

PMID- 16633537
TI  - The future of child and adolescent mental health.

PMID- 16633538
TI  - Children's right to mental health. How adults have failed youth worldwide: the
      Latin America case.

PMID- 16633539
TI  - Mental health care for children and adolescents: a regional perspective.

PMID- 16633540
TI  - Mental health care for children: the needs of African countries.

PMID- 16633541
TI  - Intervention in child abuse and neglect: an emerging subspecialty in child and
      adolescent psychiatry.

PMID- 16633543
TI  - The EUNOMIA project on coercion in psychiatry: study design and preliminary data.
AB  - Previous national research has shown significant variation in several aspects of
      coercive treatment measures in psychiatry. The EUNOMIA project, an international
      study funded by the European Commission, aims to assess the clinical practice of
      these measures and their outcomes. Its naturalistic and epidemiological design is
      being implemented at 13 centres in 12 European countries. This article describes
      the design of the study and provides preliminary data on the catchment areas,
      staff, available facilities and modalities of care at the participating centres.

PMID- 16633542
TI  - The European Prediction of Psychosis Study (EPOS): integrating early recognition
      and intervention in Europe.
AB  - This paper provides the rationale and design of the European Prediction of
      Psychosis Study (EPOS), the first European prospective transnational field study
      of the prodrome and moderating risk/resilience factors of psychosis. As different
      health systems provide different structures of care, prevention programmes will
      only be successfully implemented and sustained system-wide, if they can be
      adapted to the system's special opportunities and needs. EPOS will provide a
      sound data base for a future evidence-based prevention of psychosis. Data on the
      recruitment of subjects and on the distribution of the four clinical criteria for
      an at-risk mental state for psychosis are given.

PMID- 16633544
TI  - Relationship between cocaine use and mental health problems in a sample of
      European cocaine powder or crack users.
AB  - Numerous studies have pointed out the risks of cocaine use for mental health.
      Most clinical studies report a high psychiatric comorbidity, mainly among crack
      users. In this paper the association of mental health problems with
      sociodemographic variables and patterns of use is analysed, based on data from a
      multicentre European study including a field survey of cocaine users in different
      settings. Bivariate analyses revealed that mental health problems were influenced
      by all variables under consideration, i.e. age, gender, social situation, crack
      use, days with cocaine use in the past month, lifetime use of cocaine, severity
      of dependence, and physical health. However, in a regression analysis, intensity
      of use, physical health, severity of dependence and social situation were found
      to be predictors of mental health problems, while crack use by itself was not.
      These findings suggest that mental health consequences are related more to the
      intensity than to the form of cocaine use.

PMID- 16633545
TI  - A competencies-based mental health training model for health professionals in low
      and middle income countries.
AB  - This paper describes a competencies-based training model specifically created to
      teach needed mental health skills to health professionals in low and middle
      income countries (LMICs). The model combines a mental health training needs
      assessment with the delivery of mental health training modules aligned with
      national/regional mental health priorities and designed to be used by all health
      professionals at various levels of the health care system. The model also defines
      a sustainability framework that involves the creation of a multidisciplinary
      training team embedded in the national/regional health system. The training
      program consists of a number of modules, each one designed to enhance specific
      mental health competencies for a variety of health care workers. These modules
      are linked to a number of clinically useful tools that facilitate knowledge
      transfer into clinical care while concurrently addressing health equity issues.
      This model may provide an efficient and cost-effective alternative to traditional
      profession-based mental health training approaches, which have to date not been
      successful at meeting mental health delivery needs and mental health service
      priorities in LMICs.

PMID- 16633546
TI  - The public mental health significance of research on socio-economic factors in
      schizophrenia and major depression.
AB  - This paper reviews the epidemiological research evidence on the role of socio
      economic factors in the origins and disease experience of schizophrenia and major
      depression. The studies were conducted in different countries over many years.
      Although their findings are divided in their support of either the social
      causation or the drift hypothesis, all of them agree that persons with these
      disorders are at high disadvantage in society. Several factors for this have been
      identified. These studies provide the rationale for community-based interventions
      that have to be guided by principles of equity in the distribution of resources
      and grounded in biopsychosocial models of care that comprehensively answer the
      needs of the affected populations.

PMID- 16633547
TI  - Sleep disorders in psychiatric practice.
AB  - Over the last years, a large body of evidence has accumulated showing that
      complaints of disordered sleep are quite prevalent in the community. Insomnia is
      by far the most common disturbance and is often associated with concurrent
      psychiatric illness, in particular anxiety and mood disorders. On the other hand,
      sleep complaints are frequently present among psychiatric patients and have been
      incorporated in the official diagnostic criteria for many mental disorders, such
      as major depression, post-traumatic stress disorder, generalized anxiety disorder
      and substance-related disorders. Estimates of the prevalence of sleep disorders
      diverge widely, because these disorders have been variously conceptualized.
      Currently, however, three different classifications for sleep disorders establish
      reliable diagnostic criteria and allow for more consistency in clinical research.
      In particular, the ICD-10 diagnostic criteria for insomnia helped to establish a
      consensus among sleep specialists by defining accurately this clinical condition,
      i.e. by conceptualizing it as the subjective complaint of insufficient or non
      restorative sleep, which is the important feature, not the actual amount of time
      spent asleep. Alongside the evolution of taxonomic systems, the development of
      specific diagnostic tools, such as rating scales for measuring clinical
      manifestations of sleep disorders, has contributed significantly to the growth in
      the field. For instance, the risk factors responsible for the development of
      chronic insomnia, its consequences, and the complex relationship between insomnia
      and psychopathology, have been considerably clarified. In terms of the
      polysomnographic aberrations observed in various mental disorders, these,
      although proven not to be pathognomonic for any of them, have been considerably
      refined over the last decade, and certain general sleep patterns for some
      specific disorders have emerged. Finally, substantial advances have been made in
      the elucidation of the neuropsychobiological substrate of disturbed sleep. Thus,
      hyperarousal has been identified as the cardinal feature of chronic insomnia,
      which is associated with an around-the-clock activation of both major components
      of the stress system, the hypothalamic-pituitary-adrenal axis and the sympathetic
      nervous system.

PMID- 16633549
TI  - Femtosecond Time-Resolved Stimulated Raman Spectroscopy of the S(2) (1B(u))
      Excited State of beta-Carotene.
AB  - The electronic and vibrational structure of beta-carotene's early excited states
      are examined using femtosecond time-resolved stimulated Raman spectroscopy. The
      vibrational spectrum of the short-lived ( approximately 160 fs) second excited
      singlet state (S(2),1B(u) (+))of beta-carotene is obtained. Broad, resonantly
      enhanced vibrational features are observed at approximately 1100, 1300, and 1650
      cm(-1) that decay with a time constant corresponding to the electronic lifetime
      of S(2). The temporal evolution of the vibrational spectra are consistent with
      significant population of only two low-lying excited electronic states (1B(u) (+)
      and 2A(g) (-)) in the ultrafast relaxation pathway of beta-carotene.

PMID- 16633550
TI  - Dihydrogen Activation by Titanium Sulfide Complexes.
AB  - The titanocene sulfido complex Cp*(2)Ti(S)py (1, Cp* =
      pentamethylcyclopentadienyl; py = pyridine) is synthesized by addition of a
      suspension of S(8) to a toluene solution of Cp*(2)Ti-(CH(2)CH(2)) (2) and py. The
      rate of rotation of the pyridine ligand in solution was determined by (1)H NMR
      spectroscopy, and the structure of 1 was determined by X-ray crystallography.
      Complex 1 reacts reversibly with dihydrogen to give Cp*(2)Ti(H)SH (6) and py.
      Reaction of 1 with HD gives an equilibrium mixture of Cp*(2)Ti(D)SH and
      Cp*(2)Ti(H)SD; H(2) and D(2) are not formed in this reaction. 1D (1)H NMR
      magnetization transfer spectra and 2D EXSY (1)H NMR spectra of 6 in the presence
      of H(2) show that in solution the H(2), hydride, and hydrosulfido hydrogen atoms
      exchange. A four-center mechanism for this exchange is proposed. The EXSY studies
      show that the Ti-H and S-H hydrogens exchange with each other more rapidly than
      either of those hydrogens exchanges with external H(2). A transient dihydrogen
      complex intermediate is proposed to explain this observation. The infrared
      spectrum of 6 shows an absorption assigned to the Ti-H stretching mode at 1591
      cm(-1) that shifts upon deuteration to 1154 cm(-1). Reaction of 1 with
      trimethylsilane, diethylsilane, or dimethylsilane gives Cp*(2)-Ti(H)SSiMe(3) (7),
      Cp*(2)Ti(H)SSiHEt(2) (8), or Cp*(2)Ti(H)SSiHMe(2) (9), respectively. The isotope
      effect for the reaction producing 7 has been measured, and a mechanism is
      proposed. Treatment of 1 with an additional equivalent of S(8) results in the
      formation of the disulfide Cp*(2)Ti(S(2)) (4). Acetylene inserts into the Ti-S
      bond of 4 to produce the vinyl disulfide complex 5. The structures of 4 and 5
      have been determined by X-ray diffraction. Compound 4 reacts with 2 in the
      presence of py to produce 1. Phosphines react with 4 in the presence of H(2) to
      provide 6 and the corresponding phosphine sulfide. Reaction of hydrogen with 4
      gives Cp*(2)-Ti(SH)(2) (3). The reactions of 1 and 4 with dihydrogen provide a
      model for possible mechanisms of H(2) activation by metal-sulfide
      hydrodesulfurization catalysts.

PMID- 16633551
TI  - Synthesis and applications of amphiphilic fulleropyrrolidine derivatives.
AB  - The most successful strategies for dissolving fullerenes in polar solvents by
      means of 1,3-dipolar cycloaddition of azomethine ylides to C60 are reviewed. The
      preparation of the fullerene derivatives is discussed together with their
      properties and applications in different fields.

PMID- 16633552
TI  - Sequence-selective osmium oxidation of DNA: efficient distinction between 5
      methylcytosine and cytosine.
AB  - 5-Methylcytosine was distinguished from cytosine using the large difference of
      their osmium oxidation rates, and this reaction was applied to detection of the
      cytosine methylation status at a specific site of a long sequence using the
      formation of a bulge structure by hybridization with a guide DNA.

PMID- 16633553
TI  - Development of drug intermediates by using direct organocatalytic multi-component
      reactions.
AB  - Novel, economic and environmentally friendly one-pot three-component
      Knoevenagel/hydrogenation (K/H) and four-component
      Knoevenagel/hydrogenation/alkylation (K/H/A) reactions of ketones, CH-acids,
      dihydropyridines and alkyl halides using proline and proline/metal carbonate
      catalysis, respectively, have been developed. Many of the products of these K/H
      and K/H/A reactions have direct applications in pharmaceutical chemistry.

PMID- 16633554
TI  - Unexpected interconversion reaction of 1,4-diaminofullerenes.
AB  - A facile substitution of amine groups attached to the fullerene cage occurs when
      1,4-diaminofullerenes C60[NR2]2 are allowed to react with excess of another amine
      R'2NH; this reaction proceeds rapidly at room temperature without any additional
      initiators.

PMID- 16633555
TI  - A facile and chemoselective conjugate reduction using polymethylhydrosiloxane
      (PMHS) and catalytic B(C6F5)3.
AB  - A highly chemoselective conjugate reduction of electron-deficient Michael
      acceptors, including alpha,beta-unsaturated ketones, carboxylic esters, nitriles
      and nitro compounds with PMHS in the presence of catalytic B(C6F5)3 is described.

PMID- 16633556
TI  - Nucleophilic opening of epoxyazepanes: expanding the family of polyhydroxyazepane
      based glycosidase inhibitors.
AB  - A range of new tetra- and pentahydroxylated seven-membered iminoalditols has been
      efficiently synthesized from epoxyazepane precursors via nucleophilic opening
      with hydride or oxygenated species and subsequent hydrogenolysis. One
      tetrahydroxylated azepane, a ring homologue of deoxymannojirimycin, displays a
      selective and fairly good inhibition of alpha-L-fucosidase.

PMID- 16633557
TI  - A facile and highly efficient route to alpha-amino phosphonates via three
      component reactions catalyzed by Mg(ClO4)2 or molecular iodine.
AB  - Three-component reactions of aldehydes, amines, and diethyl phosphite catalyzed
      by Mg(ClO4)2 or molecular iodine afforded the corresponding alpha-amino
      phosphonates in excellent yields under mild reaction conditions.

PMID- 16633558
TI  - Regioselective organocatalysis: a theoretical prediction of the selective rate
      acceleration of the SN2 reaction between an acetate ion and primary alkyl
      chlorides in DMSO solution.
AB  - High level ab initio calculations, including the solvent effect through a
      continuum solvation model, predict that 1,4-benzenedimethanol is able to catalyse
      the S(N)2 reaction between an acetate ion and primary alkyl chlorides in dimethyl
      sulfoxide solution. The catalysis takes place through two selective hydrogen
      bonds to the transition state. However, for secondary alkyl chlorides the
      catalysis is not effective due to steric repulsion and desolvation. This effect
      induces regioselective control of S(N)2 esterification reactions.

PMID- 16633559
TI  - DBU catalyzed cyanoacylation of ketones with acyl cyanides.
AB  - The reaction of cyclohexanone with benzoyl cyanide catalyzed by amines provides
      the corresponding O-benzoyl cyanohydrin adducts in moderate to good yields under
      mild conditions. Among the catalysts, DBU was found to be the most effective
      promoter allowing the reaction to proceed smoothly at room temperature and to
      give the corresponding O-acyl cyanohydrin adducts in higher yields for a variety
      of substituted cyclohexanones, cyclopentanone, acetone or pentan-3-one and
      various acyl cyanides.

PMID- 16633560
TI  - The chemical nature of the 2'-substituent in the pentose-sugar dictates the
      pseudoaromatic character of the nucleobase (pKa) in DNA/RNA.
AB  - We here show that the pKa (error limit: 0.01 to 0.03 pKa unit) of a nucleobase in
      a nucleotide can be modulated by the chemical nature of the 2'-substituent at the
      sugar moiety. This has been evidenced by the measurement of nucleobase pKa in 47
      different model nucleoside 3',5'-bis- and 3'-mono-ethylphosphates. The fact that
      the electronic character of each of the 2'-substituents (Fig. 1) alters the
      chemical shift of the H2' sugar proton, and also alters the pKa of the nucleobase
      in the nucleotides has been evidenced by a correlation plot of pKa of N3 of
      pyrimidine (T/C/U) or pKa of N7 of 9-guaninyl with the corresponding deltaH2'
      chemical shifts at the neutral pH, which shows linear correlation with high
      Pearson's correlation coefficients (R = 0.85-0.97). That this modulation of the
      pKa of the nucleobase by a 2'-substituent is a through-bond as well as through
      space effect has been proven by ab initio determined pKa estimation.
      Interestingly, experimental pKas of nucleobases from NMR titration and the
      calculated pKas (by ab initio calculations utilizing closed shell HF 6-31G**
      basis set) are linearly correlated with R = 0.98. It has also been observed that
      the difference of ground and protonated/de-protonated HOMO orbital energies
      (DeltaHOMO, a.u.) for the nucleobases (A/G/C/T/U) are well correlated with their
      pK(a)s in different 2'-substituted 3',5'-bis-ethylphosphate analogs suggesting
      that only the orbital energy of HOMO can be successfully used to predict the
      modulation of the chemical reactivity of the nucleobase by the 2'-substituent. It
      has also been demonstrated that pKa values of nucleobases in 3',5'-bis
      ethylphosphates (Table 1) are well correlated with the change in dipole moment
      for the respective nucleobases after protonation or de-protonation. This work
      thus unambiguously shows that alteration of the thermodynamic stability (Tm) of
      the donor-acceptor complexes [ref. 20], as found with various 2'-modified
      duplexes in the antisense, siRNA or in triplexes by many workers in the field, is
      a result of alteration of the pseudoaromatic character of the nucleobases
      engineered by alteration of the chemical nature of the 2'-substitution.

PMID- 16633561
TI  - Crystal structures and catalytic mechanism of the Arabidopsis cinnamyl alcohol
      dehydrogenases AtCAD5 and AtCAD4.
AB  - The cinnamyl alcohol dehydrogenase (CAD) multigene family in planta encodes
      proteins catalyzing the reductions of various phenylpropenyl aldehyde derivatives
      in a substrate versatile manner, and whose metabolic products are the precursors
      of structural lignins, health-related lignans, and various other metabolites. In
      Arabidopsis thaliana, the two isoforms, AtCAD5 and AtCAD4, are the catalytically
      most active being viewed as mainly involved in the formation of guaiacyl/syringyl
      lignins. In this study, we determined the crystal structures of AtCAD5 in the apo
      form and as a binary complex with NADP+, respectively, and modeled that of
      AtCAD4. Both AtCAD5 and AtCAD4 are dimers with two zinc ions per subunit and
      belong to the Zn-dependent medium chain dehydrogenase/reductase (MDR)
      superfamily, on the basis of their overall 2-domain structures and distribution
      of secondary structural elements. The catalytic Zn2+ ions in both enzymes are
      tetrahedrally coordinated, but differ from those in horse liver alcohol
      dehydrogenase since the carboxyl side-chain of Glu70 is ligated to Zn2+ instead
      of water. Using AtCAD5, site-directed mutagenesis of Glu70 to alanine resulted in
      loss of catalytic activity, thereby indicating that perturbation of the Zn2+
      coordination was sufficient to abolish catalytic activity. The substrate-binding
      pockets of both AtCAD5 and AtCAD4 were also examined, and found to be
      significantly different and smaller compared to that of a putative aspen sinapyl
      alcohol dehydrogenase (SAD) and a putative yeast CAD. While the physiological
      roles of the aspen SAD and the yeast CAD are uncertain, they nevertheless have a
      high similarity in the overall 3D structures to AtCAD5 and 4. With the bona fide
      CAD's from various species, nine out of the twelve residues which constitute the
      proposed substrate-binding pocket were, however, conserved. This is provisionally
      considered as indicative of a characteristic fingerprint for the CAD family.

PMID- 16633562
TI  - A highly enantioselective total synthesis of (+)-goniodiol.
AB  - A high-yielding enantioselective total synthesis of the bioactive styryllactone
      (+)-goniodiol has been realised, starting from readily available (S)-glycidol. A
      key step is an oxygen-to-carbon rearrangement of a silyl enol ether linked via an
      anomeric centre, facilitating the rapid and diastereoselective construction of
      this functionalised system.

PMID- 16633563
TI  - Azaxanthones and azathioxanthones are effective sensitisers for europium and
      terbium luminescence.
AB  - Several azaxanthone and azathioxanthone sensitising chromophores have been
      incorporated into macrocyclic ligands and form well-defined Eu and Tb complexes
      in polar media. Excitation of the heterocyclic chromophore in the range 330 to
      382 nm leads to modest amounts of aromatic fluorescence and relatively efficient
      metal-based luminescence, with absolute metal-based quantum yields of up to 24%
      in aqueous media.

PMID- 16633564
TI  - The syntheses and properties of tricyclic pyrrolo[2,3-d]pyrimidine analogues of
      S6-methylthioguanine and O6-methylguanine.
AB  - The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6
      methylthioguanine are described. The crystal structures and pKa values of these
      and related O6-methylguanine analogues are reported. All compounds display higher
      pKa values than O6-methylguanine with the sulfur-containing analogues being the
      more basic and exhibiting higher stability in aqueous solution. In a standard
      substrate assay with the human repair protein O6-methylguanine-DNA
      methyltransferase (MGMT) only the oxygen-containing analogue displayed activity.

PMID- 16633565
TI  - Formulation of photocleavable liposomes and the mechanism of their content
      release.
AB  - In pursuit of designing photocleavable liposomes as drug delivery vehicles, we
      synthesized several amphiphilic lipids by connecting stearyl amine (as the non
      polar tail) and charged amino acids (as polar heads) via the o-nitrobenzyl
      derivatives. The lipids containing Glu, Asp, and Lys amino acids were subjected
      to photocleavage reaction by UV light, and the overall spectral changes of the
      chromophoric o-nitrobenzyl conjugates were determined as a function of time. The
      experimental data revealed that the feasibility of the cleavage reaction, nature
      and magnitude of the spectral changes during the course of the cleavage reaction,
      and their overall kinetic profiles were dictated by the type of amino acid
      constituting the polar head groups. The cleavage reactions of the Asp and Glu
      containing lipids were found to be more facile than that of the lysine-containing
      lipid. Using these lipids, we formulated photocleavable liposomes, and
      investigated the photo-triggered release of an encapsulated (within the liposomal
      lumen) dye as a function of time. The kinetic data revealed that the release of
      the liposomal content conformed to a two-step mechanism, of which the first
      (fast) step involved the photocleavage of lipids followed by the slow release of
      the liposomal content during the second step. The overall mechanistic features
      intrinsic to the photocleavage of Asp, Glu and Lys containing o-nitrobenzyl
      conjugated lipids, and their potential applications in formulating liposomes
      (whose contents can be "unloaded" by the UV light) as drug delivery vehicles are
      discussed.

PMID- 16633566
TI  - Ab initio base-pairing energies of uracil and 5-hydroxyuracil with standard DNA
      bases at the BSSE-free DFT and MP2 theory levels.
AB  - Oxidized cytosine product 5-hydroxyuracil has been shown to be the major chemical
      precursor for the GC to AT transition, the most frequent substitution mutation
      observed in aerobic organisms. We have calculated the interaction energy of base
      pair formation involving uracil or 5-hydroxyuracil, which is formed in cells by
      oxidative deamination of cytosine, bound to any of the natural DNA bases, A, C,
      G, and T, and discuss the effects of the hydroxyl group in this respect. The base
      pair geometries and energies were calculated using the 6-311G(dp) basis set under
      four conditions: using density functional theory (DFT) without out basis set
      super-position error (BSSE) correction, using DFT with BSSE correction of
      geometries and energies, using Moller-Plesset second order perturbation theory
      (MP2) without BSSE correction, and using MP2 with BSSE geometry and energy
      correction. We find that the hydroxyl group of 5-HO-U (relative to U) has little
      effect on the base-pairs with A, C or one conformation of T, while making a
      substantial energy difference in base-pairs involving G or a different
      conformation of T. For most of the complexes studied, the BSSE-corrected energies
      at the DFT and MP2 levels of theory agreed to within 0.5 kcal.

PMID- 16633567
TI  - Low background FRET-substrates for lipases and esterases suitable for high
      throughput screening under basic (pH 11) conditions.
AB  - FRET-based fluorogenic substrates for lipases and esterases were prepared in four
      steps from commercially available building blocks. The substrates are
      pyrenebutyric acid monoesters of aliphatic 1,2-diols bearing a dinitrophenylamino
      group as a quencher. The most enzyme-reactive substrate is ester 2a. The
      substrates do not show any measurable background reaction in the absence of
      enzyme even at pH 11, but react fast and specifically with lipases and esterases.
      These substrates offer an unprecedented and practical solution to the long
      standing problem of a simple yet efficient high-throughput screening tool for
      lipase activities under basic conditions.

PMID- 16633568
TI  - Dramatic selectivity differences in the association of DNA and RNA models with
      new ethylene- and propylene diamine derivatives and their copper complexes.
AB  - The affinities of polyamines consisting of ethylenediamine units equipped with
      either one or two terminal naphthyl-, anthryl-, or acridyl units towards
      PolyA.PolyU as an RNA model, and Poly(dA).Poly(dT) as a DNA model are screened by
      measuring the melting point changes (DeltaT(m)) of the double strands, and also
      partially by a fluorimetric binding assay using ethidium bromide. The larger
      aromatic moieties with long spacers between them allow bisintercalation; this
      leads to an increased preference for DNA in comparison to RNA, where ion pairing
      of the ammonium centers with the major RNA groove phosphates dominates.
      Allosteric affinity control by metalation is achieved e.g. with Cu(2+) ions,
      which induce conformational distortions within the chains. With anthryl- in
      contrast to naphthyl derivatives intercalation can be so strong that distortion
      of the ethylenediamine chain by metalation is not powerful enough. A particularly
      high concentration of positive charges is accessible with tripodal derivatives
      built up from ethylenediamine and propylenediamine units; in the absence of aryl
      parts, which interfere with the RNA groove preference, one observes the highest
      affinity difference known until today, reflected in a melting point ratio of
      DeltaT(m(RNA))/DeltaT(m(DNA)) = 40, whereas other synthetic ligands reach only a
      DeltaT(m(RNA))/DeltaT(m(DNA)) ratio of about 3.

PMID- 16633569
TI  - Anion binding by catechols--an NMR, optical and electrochemical study.
AB  - The X-ray structure of the ClC chloride channel made it clear that O-H...chloride
      interactions play a key role in important biological membrane-bound systems,
      however, surprisingly this type of interaction has only been rarely exploited for
      the development of synthetic anion receptors. This paper therefore reports the
      anion binding strengths and selectivities of some simple commercially available
      bis-phenols. In particular, we compare catechol (1,2-dihydroxybenzene) and
      resorcinol (1,3-dihydroxybenzene) which show interesting and different
      selectivities between the halide anions in acetonitrile solution. Catechol binds
      tetrabutylammononium (TBA) chloride almost 30 times more strongly than TBA
      bromide, whilst for resorcinol, this difference drops to a factor of ca. 3.5. It
      is suggested that this is a consequence of the bite angle of the chelating
      hydrogen bonding groups of catechol being particularly appropriate for effective
      binding of the smaller anion. The oxidation of catechol to ortho-quinone is
      perturbed by the addition of chloride anions, as probed via cyclic voltammetry,
      and this compound can therefore be considered to act as an electrochemical sensor
      for chloride. Nitrocatechol is able to bind chloride anions more strongly than
      catechol as a consequence of its enhanced acidity and hence greater hydrogen bond
      donor character. Furthermore, nitrocatechol senses the bound anion via changes in
      its UV-visible spectrum. Notably, binding still occurs even in the presence of
      small amounts of competitive solvents (e.g. water). This observation has
      biomimetic importance as wet acetonitrile has some similarity in terms of overall
      polarity and hydrogen bond competition to the solvent shielded interiors of
      biological macromolecules and membranes--such as the environment within the ClC
      chloride channel itself. Finally, we report that catechol undergoes a unique
      colorimetric response on the addition of basic anions, such as fluoride. We can
      assign this response as being due to oxidative degradation of catechol catalysed
      by the basic anions (which bind to, and deprotonate, the catechol). This process
      is somewhat analogous to the well-known metal catalysed oxidation of catechol
      which can take place in aqueous solution. The speed of response and easily
      monitored and distinctive colour change induced by fluoride anions indicates this
      may be a useful mechanism for exploitation in the development of selective
      fluoride sensors.

PMID- 16633570
TI  - Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone
      inhibitors of protein geranylgeranyltransferase-I.
AB  - A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I
      substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid
      scaffold, we have introduced critical pharmacophores in a well-defined
      arrangement to mimic the CAAL sequence. High potency and exceptional selectivity
      were obtained for inhibition of PGGTase-I with structures such as 45 and 70.
      Potency of this series of GGTIs was dependent on the presence of an L-leucine
      residue with a free carboxyl terminus, as well as an S configuration of the 3
      aryl group. The selectivity was significantly enhanced by 5-methyl substitution
      on the imidazole ring and fluorine substitution on the 3-aryl group. Modification
      of the 6-position of the piperazinone scaffold was found to be unfavorable.
      Compounds 44 and 69, the corresponding methyl esters of 45 and 70, were found to
      selectively block processing of Rap1A by PGGTase-I in whole cells with IC(50)
      values of 0.4 microM and 0.7 microM respectively.

PMID- 16633571
TI  - Electrophoresis of electrostatically assembled fullerene-porphyrin conjugates.
AB  - The formation of electrostatically coupled assemblies of a series of anionic
      dendritic fullerene derivatives and cationic porphyrins in buffered aqueous media
      was studied with gel electrophoresis. Of central interest in these investigations
      was the variation of the amount of charge carried by the molecules, their size,
      shape and self-aggregation. Ferric cytochrome c 1 and the more rigid zinc
      porphyrin served as octacationic species. The two new anionic fullerene derivates
      3 and 6 were synthesized. The formation of electrostatic complexes of the
      fullerene polyelectrolytes 3 and 4 with 1and 2 was clearly evident in the gel
      electrophoresis experiment. Compounds and showed a similar behaviour towards 2.
      The electrophoresis experiments confirmed previous results obtained with other
      techniques on a qualitative level and gave new insights into aggregation
      phenomena.

PMID- 16633572
TI  - Copper(I) mediated cross-coupling of amino acid derived organozinc reagents with
      acid chlorides.
AB  - This paper describes the development of a straightforward experimental protocol
      for copper-mediated cross-coupling of amino acid derived beta-amido-alkylzinc
      iodides 1 and 3 with a range of acid chlorides. The present method uses
      CuCN.2LiCl as the copper source and for organozinc reagent 1 the methodology
      appears to be limited to reaction with more stable acid chlorides, providing the
      desired products in moderate yields. When applied to organozinc reagent 3,
      however, the protocol is more general and provides the products in good yields in
      all but one of the cases tested.

PMID- 16633573
TI  - The conformational bias of aryl, arylsulfonyl geminally substituted tertiary
      carbon centers: applications in substrate-based stereocontrol.
AB  - Intramolecular nitrile oxide-olefin cycloaddition to form hexahydrobenzisoxazole
      14, which engenders a phenylsulfonyl, 2,5-difluorophenyl geminally substituted
      carbon substructure, proceeds with up to 99% ds. A rationalization of the high
      level of substrate-based stereo-induction observed in this and related ketone and
      acrylonitrile metallohydride reductions, supported by single crystal X-ray
      crystallography, is presented.

PMID- 16633574
TI  - Novel 6-formylpterin derivatives: chemical synthesis and O2 to ROS conversion
      activities.
AB  - 6-Formylpterin (6FP) has been demonstrated to have strong neuroprotective effects
      against transient ischemia-reperfusion injury in gerbils. Also it has been shown
      that in rats, 6FP protected retinal neurons even when it was administered after
      the ischemic insult. Since there is a significant need for such a compound that
      effectively suppresses the events caused by the lack of oxygen supply, 6FP has
      attracted further investigation. Unfortunately, however, 6FP is hardly soluble in
      water at neutral pH and in organic solvents because of its self-assembling
      ability. Although a several mM solution of 6FP is available in alkaline water, it
      is unstable. In the present study, a novel chemical derivatization of 6FP has
      been developed which maintains the formyl group on the 6-position of 6FP, which
      is essential for the physiological activities of 6FP, and increases solubility in
      water and organic solvents. In the method, the 2- and 3-positions of 6FP were
      modified by a three component coupling reaction: 6FP was subjected to the
      reaction with acid chloride and N,N-dimethylformamide. The derivatives
      synthesized here, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3
      pivaloylpteridine-4-one 1, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3
      isobutyrylpteridine-4-one 2, and 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-o
      toluoylpteridine-4-one 3, showed high solubility in water (1.0-5.6 mM) and
      organic solvents. The O(2) conversion property has also been determined for the
      derivative 1. Using an oxygen electrode, it has been found that O(2) is consumed
      in the presence of 1 and NADH at around pH 7.4 and that the rate of O(2)
      consumption is enhanced by UV-A irradiation. Electron paramagnetic resonance
      (EPR) analysis coupled with DMPO spin trapping has also revealed that in the
      presence of NADH, 1 converts O(2) to O(2)(-), which is further reduced to OH. By
      UV-A illumination in the analogous systems, (1)O(2) formation was observed. These
      results are similar to those reported previously for 6FP.

PMID- 16633575
TI  - Mannose-pepstatin conjugates as targeted inhibitors of antigen processing.
AB  - The molecular details of antigen processing, including the identity of the
      enzymes involved, their intracellular location and their substrate specificity,
      are still incompletely understood. Selective inhibition of proteolytic antigen
      processing enzymes such as cathepsins D and E, using small molecular inhibitors
      such as pepstatin, has proven to be a valuable tool in investigating these
      pathways. However, pepstatin is poorly soluble in water and has limited access to
      the antigen processing compartment in antigen presenting cells. We have
      synthesised mannose-pepstatin conjugates, and neomannosylated BSA-pepstatin
      conjugates, as tools for the in vivo study of the antigen processing pathway.
      Conjugation to mannose and to neomannosylated BSA substantially improved the
      solubility of the conjugates relative to pepstatin. The mannose-pepstatin
      conjugates showed no reduction in inhibition of cathepsin E, whereas the
      neomannosylated BSA-pepstatin conjugates showed some loss of inhibition, probably
      due to steric factors. However, a neomannosylated BSA-pepstatin conjugate
      incorporating a cleavable disulfide linkage between the pepstatin and the BSA
      showed the best uptake to dendritic cells and the best inhibition of antigen
      processing.

PMID- 16633576
TI  - Tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence.
AB  - This paper critically reviews analytical applications of the chemiluminescence
      from tris(2,2'-bipyridyl)ruthenium(II) and related compounds published in the
      open literature between mid-1998 and October 2005. Following the introduction,
      which summarises the reaction chemistry and reagent generation, the review
      divides into three major sections that focus on: (i) the techniques that utilise
      this type of detection chemistry, (ii) the range of analytes that can be
      determined, and (iii) analogues and derivatives of tris(2,2'
      bipyridyl)ruthenium(II).

PMID- 16633577
TI  - Analytical performances of FT-IR spectrometry and imaging for concentration
      measurements within biological fluids, cells, and tissues.
AB  - FT-IR spectrometry has proved to be a useful tool for determining a series of
      plasma molecular concentrations. Dedicated experiments were first performed to
      test the analytical performance that could be obtained by FT-IR spectrometry
      using a synthesized N3-peptide exhibiting a -N3 absorption centered at 2110 cm(
      1), a spectral region where no organic material of biological samples absorbs.
      Further, we investigated whether this technology was able to allow quantification
      of metabolic parameters (glucose and lactic acid) within plasma, cells, and
      tissues as an alternative method to the "classical" biochemical approaches, which
      require sophisticated biological material treatment and expensive reagents. For
      this purpose we used a series of plasma samples to determine glucose and lactic
      acid concentrations, which are common markers of cancer growth. We compared the
      results of the main spectral data treatments commonly achieved for FT-IR data
      analysis, such as univariate (Beer-Lambert) or multivariate (PLS) calibrations,
      as well as the deconvolution of the spectral interval of interest (1200-900 cm(
      1)). No significant differences were found regarding the analytical performances
      of these methods. Spectral deconvolution was finally undertaken on cultured and
      on xenografted cells (U87 glial cells implied in human gliomas) to determine
      glucose and lactic acid concentrations. In this case, qualification was allowed
      by FT-IR imaging on the cellular models since biochemical approaches are not
      efficient to reach metabolic concentrations at the cellular level while keeping
      tissue organization.

PMID- 16633578
TI  - In vitro biotransformation of an arsenosugar by mouse anaerobic cecal microflora
      and cecal tissue as examined using IC-ICP-MS and LC-ESI-MS/MS.
AB  - This investigation examined chemical and microbiological transformations of an
      arsenosugar by mouse cecum. To mimic the low oxygen environment in the mammalian
      gastrointestinal tract, reaction mixtures were incubated under anaerobic
      conditions. An arsenosugar extracted from ribbon kelp, 3-[5'-deoxy-5
      (dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid, As392,
      was added to reaction mixtures that contained either cecal microflora or cecal
      tissue homogenate. These reaction mixtures were incubated at 0 or 37 degrees C
      for up to 48 hours to monitor biotransformation of the arsenosugar. Analysis of
      the reaction mixtures by IC-ICP-MS and LC-ESI-MS/MS indicated that the
      arsenosugar was converted primarily (95%) to its sulfur analog in less than 1 h
      at 37 degrees C. Conversion of As392 to its sulfur analog was much slower at 0
      degrees C (21% conversion after 48 h). In reaction mixtures with cecal tissue
      homogenate, conversion of As392 to its sulfur analog was slower (77% conversion
      after 48 h at 37 degrees C). A good mass balance was found in all reaction
      mixtures between the amount of arsenosugar added and the sum of all detected
      arsenic-containing products. LC-ESI-MS/MS spectra of the sulfur-containing
      arsenosugar formed in all reaction mixtures containing cecal microflora compared
      well with those of a synthetic standard. These results suggest that the anaerobic
      microflora of the gastrointestinal tract can rapidly convert ingested
      arsenosugars to sulfur analogs. This biotransformation may affect the subsequent
      absorption, metabolism, and disposition of arsenic present in arsenosugars.

PMID- 16633579
TI  - Efficient protein digestion with peptide separation in a micro-device interfaced
      to electrospray mass spectrometry.
AB  - A highly efficient protein digestion device has been fabricated using
      commercially available immobilized trypsin on agarose beads, packed into a silica
      capillary and connected either directly to an electrospray mass spectrometer via
      a 'microtight T' connector, from which aqueous acetic acid (0.2%) was pumped, or
      via a monolithic column connected to the mass spectrometer ion source. Six
      proteins with molecular mass ranging from 2848 to 77703 Da were digested
      completely using this system. In the second set of experiments a short monolithic
      separation column was placed after the immobilized trypsin capillary and partial
      separation of the generated peptides was obtained. The detection limits were
      increased from the micromol to pmol range by utilization of this separation
      column. Gradient elution, using a binary HPLC pump and a flow splitter, was used
      to optimize the peptide separation. This provided significantly enhanced
      resolution of the tryptic peptides but increased the analysis time to 30 minutes.

PMID- 16633580
TI  - Low-picomolar limits of detection using high-power light-emitting diodes for
      fluorescence.
AB  - Fluorescence detectors are ever more frequently being used with light-emitting
      diodes (LEDs) as the light source. Technological advances in the solid-state
      lighting industry have produced LEDs which are also suitable tools in analytical
      measurements. LEDs are now available which deliver 700 mW of radiometric power.
      While this greater light power can increase the fluorescence signal, it is not
      trivial to make proper use of this light. This new generation of LEDs has a large
      emitting area and a highly divergent beam. This presents a classic problem in
      optics where one must choose between either a small focused light spot, or high
      light collection efficiency. We have selected for light collection efficiency,
      which yields a light spot somewhat larger than the emitting area of the LED. This
      light is focused onto a flow cell. Increasing the detector cell internal diameter
      (i.d.) produces gains in (sensitivity)3. However, since the detector cell i.d. is
      smaller than the LED spot size, scattering of excitation light towards the
      detector remains a significant source of background signal. This can be minimized
      through the use of spectral filters and spatial filters in the form of pinholes.
      The detector produced a limit of detection (LOD) of 3 pM, which is roughly three
      orders of magnitude lower than other reports of LED-based fluorescence detectors.
      Furthermore, this LOD comes within a factor of six of much more expensive laser
      based fluorescence systems. This detector has been used to monitor a separation
      from a gel filtration column of fluorescently labeled BSA from residual labeling
      reagent. The LOD of fluorescently labeled BSA is 25 pM.

PMID- 16633581
TI  - Electrochemically polymerised composites of multi-walled carbon nanotubes and
      poly(vinylferrocene) and their use as modified electrodes: application to glucose
      sensing.
AB  - We report electrochemical composites of multi-walled carbon nanotubes (MWCNTs)
      with poly(vinylferrocene) (PVF). The polymeric architecture is prepared by first
      immobilising the MWCNTs onto a glassy carbon substrate, which acts to introduce
      electrical current into the composite, with the MWCNTs acting as 'molecular
      wires'. PVF films of varying surface coverages can be obtained by simply
      controlling the time a constant potential of +0.7 V (vs. Ag) wire is applied;
      with the characteristics of the derivatised MWCNTs examined by cyclic voltammetry
      and scanning electron microscopy. The application of the composite for glucose
      determination in aqueous solutions was investigated using linear sweep
      voltammetry, where it was found that the composites supported on glassy carbon
      substrates are superior to bare glassy carbon electrodes polymerised with PVF,
      likely due to the comparatively higher number of electrocatalytic centres in the
      former. This protocol was successfully transferred to prepare a PVF-MWCNT-paste
      electrode which was applied to glucose detection in diluted laked horse blood.
      The obtained results show potential and promising practical application for the
      polymer-derivatised MWCNT-modified electrodes in amperometric sensors for glucose
      determination.

PMID- 16633582
TI  - Use of fluorescence shift and fluorescence anisotropy to evaluate the re-binding
      of template to (S)-propranolol imprinted polymers.
AB  - The binding of (R)- and (S)-propranolol to an (S)-propranolol imprinted polymer
      in organic and aqueous solutions has been studied using fluorescence. The amount
      of propranolol that binds can be measured by separating non-bound propranolol
      from the polymer by centrifugation, and measuring the fluorescence intensity.
      However, this work demonstrates that other measurements can indicate how much
      propranolol has bound without the need to separate bound and non-bound analyte.
      In toluene + 0.5% AcOH, and in aqueous buffer (25 mM citrate pH 6 + 0.5% Triton
      X100) the fluorescence anisotropy increases as the fraction of analyte bound to
      the polymer increases. In aqueous buffer, binding to the polymer is also
      accompanied by a change in the relative intensities of fluorescence at 322 nm and
      at 352 nm. These non-separation techniques have been used to show that the
      imprinted polymer binds more (S)-propranolol than a non-imprinted polymer, and at
      least in organic solvent, shows selectivity for (S)- over (R)-propranolol.

PMID- 16633583
TI  - Moment combined partial least squares (MC-PLS) as an improved quantitative
      calibration method: application to the analyses of petroleum and petrochemical
      products.
AB  - A new quantitative calibration algorithm, called "Moment Combined Partial Least
      Squares (MC-PLS)", which combines the moment of spectrum and conventional PLS was
      proposed. Its calibration performance was evaluated for the analyses of three
      import petroleum and petrochemical products: gasoline, naphtha and polyol
      samples. The selected properties for these products included the research octane
      number (RON) and Reid vapor pressure (RVP) for gasoline, the distillation
      temperature at 10% (D 10%) for naphtha and the hydroxyl (OH) number for polyol.
      The major concept presented here used the moment to find the closest spectrum of
      a sample in a given dataset, and generate the difference spectrum and the
      corresponding difference in the property. These difference spectra and property
      differences were then used for PLS calibration. The moment has been employed in
      spectroscopic fields as a simple and effective "spectral feature characteristic"
      using just a few scalar values (moments). MC-PLS showed improved prediction
      performance over PLS for each case. In MC-PLS, the difference spectra generated
      using the moments were used as explained; therefore, additional detail in
      spectral variations can be utilized for calibrations. Additionally, the
      difference in the property was employed as reference data, so that its variation
      range was smaller when compared with that of the original property. Consequently,
      the MC-PLS performance could be better since the feature-enhanced spectra were
      used to model a narrower range of property variations. In the case of the D 10%
      prediction for naphtha, a non-linear prediction pattern that occurred in
      conventional PLS was effectively corrected using the MC-PLS method.

PMID- 16633584
TI  - Probing the competition between secondary structures and local preferences in gas
      phase isolated peptide backbones.
AB  - Combining laser desorption with a supersonic expansion together with the
      selectivity of IR/UV double resonance spectroscopy makes it possible to isolate
      and characterise the gas phase of remarkable backbone conformations of short
      peptide chains mimicking protein segments. A systematic bottom-up approach
      involving a conformer-specific IR study of peptide sequences of increasing sizes
      has enabled us to map the spectral signatures of the intramolecular interactions,
      which shape the peptide backbone, in particular H-bonds. The precise data
      collected are directly comparable to the most sophisticated quantum chemistry
      calculations of these species and therefore constitute a stringent test for the
      theoretical methods used. One-residue chains reveal the local conformational
      preference of the backbone and its dependence upon the nature of the residue. The
      investigation of longer chains provides evidence for a competition between simple
      successions of local conformational preferences along the chain and more folded
      structures, in which a new H-bonding network, involving distant H-bonding sites
      along the backbone, takes place. From three residues, the issue of helical
      folding can also be addressed. The present review of the gas phase literature
      data emphasizes the observation of remarkable secondary structures of biology,
      including short segments of beta-strands, gamma- and beta-turns, combinations of
      turns, including a 3(10) helix. It also provides evidence for the flexibility of
      the peptide chains, i.e., a critical influence of rather minor interactions (like
      side-chain/backbone interactions) on the conformational stability. Finally, the
      paper will discuss future promising directions of the present approach.

PMID- 16633585
TI  - On the energy landscapes of 3-indole acetic acid and 3-indole propionic acid. A
      study of side chain flexibilities in their S(0) and S(1) electronic states.
AB  - The tandem of 3-indole acetic acid (IAA) and 3-indole propionic acid (IPA) is
      ideally suited for a detailed study of the intramolecular forces responsible for
      the conformational properties of species containing side chains. Toward this end,
      high resolution S(1)<-- S(0) excitation spectra of the three origin bands in IAA
      and the two origin bands in IPA were recorded and analyzed. Each origin is
      assigned to a unique conformer. A discussion of the resulting energy landscape is
      given.

PMID- 16633586
TI  - Accurate Coulomb-fitting basis sets for H to Rn.
AB  - A series of auxiliary basis sets to fit Coulomb potentials for the elements H to
      Rn (except lanthanides) is presented. For each element only one auxiliary basis
      set is needed to approximate Coulomb energies in conjunction with orbital basis
      sets of split valence, triple zeta valence and quadruple zeta valence quality
      with errors of typically below ca. 0.15 kJ mol(-1) per atom; this was
      demonstrated in conjunction with the recently developed orbital basis sets of
      types def2-SV(P), def2-TZVP and def2-QZVPP for a large set of small molecules
      representing (nearly) each element in all of its common oxidation states. These
      auxiliary bases are slightly more than three times larger than orbital bases of
      split valence quality. Compared to non-approximated treatments, computation times
      for the Coulomb part are reduced by a factor of ca. 8 for def2-SV(P) orbital
      bases, ca. 25 for def2-TZVP and ca. 100 for def2-QZVPP orbital bases.

PMID- 16633587
TI  - Reaction dynamics simulations of the identity S(N)2 reaction H(2)O + HOOH(2)(+)-
      > H(2)OOH(+)+ H(2)O. Requirements for reaction and competition with proton
      transfer.
AB  - Despite the fact that the transition structure of the gas phase S(N)2 reaction
      H(2)O + HOOH(2)(+)--> HOOH(2)(+)+ H(2)O is well below the reactants in potential
      energy, the reaction has not yet been observed by experiment. Variational
      transition state RRKM theory reveals a strong preference for the competing proton
      transfer reaction H(2)O + HOOH(2)(+)--> H(3)O(+)+ HOOH due to entropy factors.
      Born-Oppenheimer reaction dynamics simulations confirm these results. However, by
      increasing the collision energy to around 7.5 eV the probability for nucleophilic
      substitution increases relative to proton transfer. These observations are
      explained by the presence of the key common intermediate HOO(H)[dot dot dot]H
      OH(2)(+) which leads to effective proton transfer, but can be avoided with
      increasing collision energy. However, the S(N)2 probability remains below 0.2
      since successful passage through the TS requires optimum initial orientation of
      the reactants, excitation of the relative translational motion and good phase
      correlation between the O-O vibration and the motion of the incoming water.

PMID- 16633588
TI  - Tunneling in the reaction of acetone with OH.
AB  - Based on recent detailed quantum mechanical computations of the mechanism of the
      title reaction and, this paper presents kinetics analysis of the overall rate
      constant and its temperature dependence, for which ample experimental data are
      available for comparison. The analysis confirms that the principal channel is the
      formation of acetonyl radical + H(2)O, while the channel leading to acetic acid
      is of negligible importance. It is shown that the unusual temperature dependence
      of the overall rate constant, as observed experimentally, is well accounted for
      by standard RRKM treatment that includes tunneling. This treatment is applied at
      the microcanonical level, with chemically activated distribution of entrance
      species, i.e. using a stationary rather than a thermal distribution that
      incorporates collisional energy transfer and competition between the
      redissociation and exit channel. A similar procedure is applied to the isotopic
      reaction acetone-d6 + OH with equally satisfying results, so that the
      experimental temperature dependence of the KIE (kinetic isotope effect) is
      perfectly reproduced. This very good agreement between calculation and experiment
      is obtained without any fitting to experimental values and without any adjustment
      of the parameters of calculation.

PMID- 16633589
TI  - Quantum yields for OH production in the photodissociation of HNO(3) at 248 and
      308 nm and H(2)O(2) at 308 and 320 nm.
AB  - The quantum yields for OH formation from the photolysis of HNO(3) were measured
      to be (0.88 +/- 0.09) at 248 and (1.05 +/- 0.29) at 308 nm and of H(2)O(2) to be
      (1.93 +/- 0.39) at 308 and (1.96 +/- 0.50) at 320 nm. The quoted uncertainties
      are at the 95% confidence level and include estimated systematic uncertainties.
      OH radicals were produced using pulsed laser photolysis and monitored using
      pulsed laser-induced fluorescence. Quantum yields were measured relative to the
      OH quantum yields from a reference system. The measured quantum yields at 248 nm
      are in agreement with previous direct determinations. The quantum yield values at
      308 and 320 nm are the first direct quantum yield measurements at these
      wavelengths and confirm the values currently recommended for atmospheric model
      calculations. Rate coefficients (at 298 K) for the OH + H(2)O(2) and OH + HNO(3)
      + M (in 100 Torr of N(2)) reactions were measured during this study to be (1.99
      +/- 0.16) x 10(-12) cm(3) molecule(-1) s(-1) and (1.44 +/- 0.12) x 10(-13) cm(3)
      molecule(-1) s(-1), respectively.

PMID- 16633590
TI  - Hybrid integral equation/simulation model for enhancing free energy computations.
AB  - Integral equation theory is used for extrapolating free energy data from
      molecular simulations of a reference state with respect to a modification of the
      interaction potential. The methodology is applied to the correction of artefacts
      arising from potential shifting and truncation. Corrective contributions for the
      hydration free energy with respect to the full potential are analysed for the
      case that both the solute-solvent as well as the solvent-solvent potentials are
      truncated and modified by a shifted-force term, reaching beyond the range of the
      dielectric continuum approximation and simple long-range correction expressions.
      The model systems argon in water and pure water are used as examples for apolar
      and polar solutes, revealing significant correction contributions even for the
      short-ranged dispersive interactions and the magnitude of solute-solvent and
      solvent-solvent components. In comparison with simulation-based extrapolation
      techniques the integral equation method is shown to be capable of quantitatively
      predicting truncation artefacts at negligible computational overhead.

PMID- 16633591
TI  - A novel united-atom force field for imidazolium-based ionic liquids.
AB  - A novel united-atom (UA) force field is proposed from our previously developed
      all-atom (AA) force field for the imidazolium-based ionic liquids by the
      introduction of a coarse-grained method. The Lennard-Jones parameters for CH(2)
      and CH(3) in alkyls are fitted to match the AA force field, and the partial
      atomic charges are re-fitted by the one conformation two-step RESP method. The
      force field is verified by molecular dynamics simulations of pure ionic liquids
      and the mixture of [bmim][BF(4)] and acetonitrile. The densities, self-diffusion
      coefficients, vaporization enthalpies, cohesive energy densities, and microscopic
      structures of both the pure components and mixtures are simulated. The simulated
      results from the UA force field agree well with those from the AA force field. In
      addition, the predictive capability of the UA force field for the liquid
      densities of [C(n)mim][PF(6)] is tested. The UA force field proposed in this work
      provides a useful tool with good accuracy and much less computational intensity
      for future molecular design of ionic liquids.

PMID- 16633592
TI  - On the origin of the lattice constant anomaly in nanocrystalline ceria.
AB  - The lattice parameter of nanocrystalline ceria films prepared by sputtering was
      monitored as a function of annealing temperature. Within the temperature range of
      150-420 degrees C, an equilibrium with atmospheric oxygen is established within a
      few hours, whereas grain growth does not occur. On the basis of the experimental
      results and analysis of literature data, we present a model that posits the
      formation of a non-uniform grain structure with stoichiometric interiors and
      oxygen deficient boundaries. This model, based on defect thermodynamics,
      correctly describes the dependence of the lattice parameter of nanocrystalline
      ceria on annealing temperature and grain size and can be extended to other
      materials as well.

PMID- 16633593
TI  - Photodegradation of toluene over TiO(2-x)N(x) under visible light irradiation.
AB  - We report the photooxidation of toluene over nitrogen doped TiO(2) (TiO(2-x)N(x))
      under visible light irradiation. The photocatalytic oxidation of toluene in air
      over TiO(2-x)N(x) powders was studied using diffuse reflectance Fourier transform
      infrared spectroscopy (DRIFTS), gas chromatography (GC), ion chromatography (IC),
      and gas chromatography mass spectrometry (GC-MS), focusing on the photocatalytic
      decomposition processes of toluene. Results obtained indicate that toluene,
      weakly adsorbed on the catalyst surface, is initially photooxidized to
      benzaldehyde which adsorbs onto the TiO(2-x)N(x) surface more strongly, leading
      to the formation of ring-opening products such as carboxylic acids and aldehydes.
      No gaseous intermediates were detected during the photooxidation. Major
      intermediates adsorbed at the catalyst surface were oxalic acid, (COOH)(2),
      acetic acid, CH(3)COOH, formic acid, HCOOH, and pyruvic acid, CH(3)COCOOH,
      whereas more complicated carboxylic species, including propionic acid,
      CH(3)CH(2)COOH, isovaleric acid, (CH(3))(2)CHCH(2)COOH, and succinic acid,
      (CH(2)COOH)(2), were also found in the early stage of the photooxidation. These
      intermediate products were gradually photodegraded to CO(2) and H(2)O under
      visible light irradiation.

PMID- 16633594
TI  - Predictive theory for the combination kinetics of two alkyl radicals.
AB  - An ab initio transition state theory based procedure for accurately predicting
      the combination kinetics of two alkyl radicals is described. This procedure
      employs direct evaluations of the orientation dependent interaction energies at
      the CASPT2/cc-pvdz level within variable reaction coordinate transition state
      theory (VRC-TST). One-dimensional corrections to these energies are obtained from
      CAS+1+2/aug-cc-pvtz calculations for CH3 + CH3 along its combination reaction
      path. Direct CAS+1+2/aug-cc-pvtz calculations demonstrate that, at least for the
      purpose of predicting the kinetics, the corrected CASPT2/cc-pvdz potential energy
      surface is an accurate approximation to the CAS+1+2/aug-cc-pvtz surface.
      Furthermore, direct trajectory simulations, performed at the B3LYP/6-31G* level,
      indicate that there is little local recrossing of the optimal VRC transition
      state dividing surface. The corrected CASPT2/cc-pvdz potential is employed in
      obtaining direct VRC-TST kinetic predictions for the self and cross combinations
      of methyl, ethyl, iso-propyl, and tert-butyl radicals. Comparisons with
      experiment suggest that the present dynamically corrected VRC-TST approach
      provides quantitatively accurate predictions for the capture rate. Each
      additional methyl substituent adjacent to a radical site is found to reduce the
      rate coefficient by about a factor of two. In each instance, the rate
      coefficients are predicted to decrease quite substantially with increasing
      temperature, with the more sterically hindered reactants having a more rapid
      decrease. The simple geometric mean rule, relating the capture rate for the cross
      reaction to those for the self-reactions, is in remarkably good agreement with
      the more detailed predictions. With suitable generalizations the present approach
      should be applicable to a wide array of radical-radical combination reactions.

PMID- 16633595
TI  - Size-selected methyl lactate clusters: fragmentation and spectroscopic
      fingerprints of chiral recognition.
AB  - A comprehensive experimental study of the OH stretching vibrations of size
      selected clusters of enantiopure and racemic methyl lactate is presented. For the
      size selection, we measured angular dependent mass spectra and time-of-flight
      distributions at the different fragment masses. In this way the fragmentation of
      these clusters upon electron impact ionization is obtained. The largest fragment
      masses of the neutral (MLac)n clusters are the protonated (MLac)n-1H+ ions. The
      results of a pressure dependent study in an FTIR jet experiment are compared with
      completely size-selected experiments based on atomic beam deflection and
      depletion spectroscopy. The size assignments and spectra agree for dimers and
      trimers. Structures and spectral information for the trimer and the tetramer at
      density functional and MP2 level are provided. Selective self-aggregation and
      chiral recognition was observed for homochiral trimers. They exhibit a ring
      structure bound by OH...OH hydrogen bonds. A spectacular switch in the hydrogen
      bonding topology was observed for the tetramer. The homochiral enantiomer
      exhibits cooperative OH...OH bonding, while the heterochiral version shows
      isolated OH...O=C bonding in a symmetric SRSR arrangement. The crucial
      ingredients for this identification are the size-selective IR spectra with their
      different shifts and line patterns which are reproduced by the calculations.

PMID- 16633596
TI  - Distributed memory parallel implementation of energies and gradients for second
      order Moller-Plesset perturbation theory with the resolution-of-the-identity
      approximation.
AB  - We present a parallel implementation of second-order Moller-Plesset perturbation
      theory with the resolution-of-the-identity approximation (RI-MP2). The
      implementation is based on a recent improved sequential implementation of RI-MP2
      within the Turbomole program package and employs the message passing interface
      (MPI) standard for communication between distributed memory nodes. The parallel
      implementation extends the applicability of canonical MP2 to considerably larger
      systems. Examples are presented for full geometry optimizations with up to 60
      atoms and 3300 basis functions and MP2 energy calculations with more than 200
      atoms and 7000 basis functions.

PMID- 16633597
TI  - DFT and MD studies on the influence of the orientation of ester linkage groups in
      banana-shaped mesogens.
AB  - The influence of the direction of ester linkage groups on the structural and
      electronic properties of five-ring banana-shaped molecules with a central 1,3
      phenylene unit has been investigated including hexyloxy and dodecyloxy terminal
      chains. DFT studies on the B3LYP/6-31G(d) level were performed on the
      conformational behaviour of the ten isomers in a systematic way. The one- and two
      fold potential energy scans show that the flexibility of the wings significantly
      depends on the orientation of the carboxyl linkage groups. Moreover, the
      different directions of the carboxyl groups between the aromatic rings cause
      remarkable changes on the dipole moment and its components of the molecules.
      These findings are supported by investigations on the global charge pattern of
      the molecules calculated from electrostatic potential group charges. The bending
      angle alpha obtained from a simple model for the five-ring bent-core molecules is
      a characteristic structural parameter which can be correlated with experimental
      findings. Calculations on the bent-core molecules in an external electric dipole
      field related to the direction of their polar axis show remarkable effects with
      respect to the flexibility and polarity of the isomers. First molecular dynamics
      simulations on the banana-shaped molecules were carried out within the AMBER 7
      package. The trajectories of relevant structural parameters support the findings
      of the DFT studies. The results concerning the structure and polarity revealed
      from the DFT and MD calculations of the ten isomers can be correlated with data
      from dielectric measurements and mesophase properties.

PMID- 16633598
TI  - Raman spectroscopic study of the structure of water in aqueous solutions of
      amphoteric polymers.
AB  - Methacrylic acid (MA) and [3-(methacryloylamino)propyl]trimethylammonium chloride
      (MAPTAC) were polymerized to give amphoteric copolymers with various
      compositions. The structure and H-bonding of water in an aqueous solution of the
      copolymer were analyzed using the contours of the O-H stretching in the polarized
      Raman spectra. For comparison, the H-bonded network structure of aqueous
      solutions of homopolymers (polyMA and polyMAPTAC) was also examined. From the
      relative intensity of the collective band (C value) corresponding to a long range
      coupling of the O-H stretching in the aqueous polymer solutions, the number of H
      bonds disrupted due to the presence of one monomer residue of the polymers
      (Ncorr) was determined. The Ncorr value for polyMA was largely positive, and with
      an increase in the content of the MAPTAC residue, the Ncorr value became smaller,
      and after passing a minimum (which was still slightly positive) at a roughly
      equivalent molar ratio, the Ncorr value increased again. This is in significant
      contrast with the larger positive Ncorr values for the homopolymers (both polyMA
      and polyMAPTAC), and other ordinary polyelectrolytes such as sodium
      polyethylenesulfonate, poly-L-lysine hydrobromide and sodium polyacrylate.
      Furthermore, the Ncorr value for the copolymer (MA ratio MAPTAC = 56:44) became
      much smaller by the neutralization of MA residues in the copolymer with sodium
      hydroxide, and comparable to those for neutral polymers such as poly(ethylene
      glycol) and poly(N-vinylpyrrolidone) and zwitterionic polymers such as poly(2
      methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[3-sulfo-N,N-dimethyl-N
      (3'-methacryloylaminopropyl)propanaminium inner salt]. The present results
      clearly indicate that the amphoteric polymers with comparative contents of
      cationic and anionic groups do not significantly disturb the H-bonded network
      structure of water, probably due to the counteraction of the electrostatic
      hydration effect by the proximity between the anionic and cationic side groups.

PMID- 16633599
TI  - Vibrational and thermodynamic properties of Ar, N2, O2, H2 and CO adsorbed and
      condensed into (H,Na)-Y zeolite cages as studied by variable temperature IR
      spectroscopy.
AB  - The adsorption of Ar, H2, O2, N2 and CO on (H,Na)-Y zeolite (Si/Al = 2.9, H+/Na+
      approximately 5) has been studied at variable-temperature (90-20 K) and sub
      atmospheric pressure (0-40 mbar) by FTIR spectroscopy. Unprecedented filling
      conditions of the zeolite cavities were attained, which allowed the investigation
      of very weakly adsorbed species and of condensed, liquid-like or solid-like,
      phases. Two pressure regimes were singled out, characterized by: (i) specific
      interaction at low pressure of the probe molecules (P) with the internal Bronsted
      and Lewis sites, and (ii) multilayer adsorption at higher pressure. In the case
      of CO the perturbation of the protonic sites located inside the sodalite cages
      was also observed. As the molecule is too large to penetrate the sodalite cage,
      the perturbation is thought to involve a proton jump tunneling mechanism. The
      adsorption energy for the (HF)OH...P (P = Ar, H2, O2, N2 and CO) specific
      interaction involving the high frequency Bronsted acid sites exposed in the
      supercages was derived following the VTIR (variable temperature infrared
      spectroscopy) method described by E. Garrone and C. Otero Arean (Chem. Soc. Rev.,
      2005, 34, 846).

PMID- 16633600
TI  - Solid state fluorescence of Pigment Yellow 101 and derivatives: a conserved
      property of the individual molecules.
AB  - The optical properties of the bisazomethine pigments Pigment Yellow 101 (P.Y.101)
      and three derivatives are investigated employing density functional theory (DFT)
      and time-dependent DFT (TDDFT). P.Y.101 and one of its derivatives exhibit
      unusual solid state fluorescence, although both possess OH groups and the latter
      pigment has particularly small intermolecular distances in its crystal, which are
      both properties that contradict common empirical rules for fluorescent pigments.
      Here it is shown that the OH groups are indeed essential for molecular
      fluorescence of the pigments due to the necessary formation of an intramolecular
      hydrogen bond with the lone pairs of the bisazomethine nitrogens. Furthermore,
      the quenching mechanism of molecular fluorescence in the non-fluorescent
      derivatives is analyzed in detail and a CNN bending motion of the central
      bisazomethine substructure is identified to be the relevant reaction coordinate
      along which efficient fluorescence quenching occurs in the individual molecule as
      well as in the crystal. Electron transfer quenching, which usually is expected to
      be an important quenching mechanism in aggregated media (here the crystals), is
      ruled out for the studied bisazomethine pigments. The solid state fluorescence
      properties of the pigments can finally be understood as conserved molecular
      properties of the individual pigment molecules.

PMID- 16633601
TI  - Formation of phenol and carbonyls from the atmospheric reaction of OH radicals
      with benzene.
AB  - The gas-phase reaction of OH radicals with benzene has been studied in a flow
      tube operated at 295 +/- 2 K and 950 mbar of synthetic air or O2. Ozonolysis of
      tetramethylethylene (dark reaction) with a measured OH radical yield of 0.92 +/-
      0.08 or photolysis of methyl nitrite in the presence of NO served as the OH
      sources. For investigations in the presence of NOx, the conditions were chosen so
      that more than 95% of the OH/benzene adduct reacted with O2 even for the highest
      NO2 concentration occurring in the experiment. In the absence of NOx, a phenol
      yield from the reaction of OH radicals with benzene of 0.61 +/- 0.07 was measured
      by means of long-path FT-IR and UV spectroscopy over a wide range of experimental
      conditions. This yield was confirmed by measurements performed in the presence of
      NOx. Detected carbonyls were glyoxal, cis-butenedial and trans-butenedial with
      formation yields of 0.29 +/- 0.10, 0.08 +/- 0.03 and 0.023 +/- 0.007,
      respectively, measured in synthetic air and in the presence of NOx. There was no
      significant difference in the product yields applying both experimental
      approaches for OH generation (dark reaction or photolysis). Nitrobenzene and o
      nitrophenol were detected in traces. The yield of nitrobenzene increased with
      increasing NOx resulting in a maximum formation yield of 0.007. The detected
      products in the presence of NOx account for approximately 78% of the reacted
      carbon. Butenedial yields from benzene degradation are reported for the first
      time. In the absence of NOx, glyoxal, cis-butenedial and trans-butenedial were
      also detected, but with distinctly lower yields compared to the experiments with
      NOx.

PMID- 16633602
TI  - 10-100 eV Ar+ ion induced damage to D-ribose and 2-deoxy-D-ribose molecules in
      condensed phase.
AB  - We report that 10-100 eV Ar+ ion irradiation induces severe damage to the
      biologically relevant sugar molecules D-ribose and 2-deoxy-D-ribose in the
      condensed phase on a polycrystalline Pt substrate. Ar+ ions with kinetic energies
      down to 15 eV induce effective decomposition of both sugar molecules, leading to
      the desorption of abundant cation and anion fragments, including CH3+, C2H3+,
      C3H3+, H3O+, CHO+, CH3O+, C2H3O+, H-, O-, and OH-, etc. Use of isotopically
      labelled molecules (5- 13C D-ribose and 1-D D-ribose) reveals the site
      specificity for some of the fragment origins, and thus the nature of the chemical
      bond breaking. It is found that all of the chemical bonds in both molecules are
      vulnerable to ion impact at energies down to 15 eV, particularly both the endo-
      and exocyclic C-O bonds. In addition to molecular fragmentation, several chemical
      reactions are also observed. A small amount of O-/O fragments abstract hydrogen
      to form OH-. It is found that the formation of the H3O+ ion is related to the
      hydroxyl groups of the sugar molecules, and is associated with additional
      hydrogen loss from the parent or adjacent molecules via hydrogen abstraction or
      proton transfer. The formation of several other cation fragments also requires
      hydrogen abstraction from its parent or an adjacent molecule. These
      fragmentations and reactions are likely to occur in a real biomedium during
      ionizing radiation treatment of tumors and thus bear significant radiobiological
      relevance.

PMID- 16633603
TI  - Rh-V alloy formation in Rh-VOx thin films after high-temperature reduction
      studied by electron microscopy.
AB  - Rh nanoparticles (mean size 10 and 15 nm), prepared by epitaxial growth on NaCl
      surfaces, were covered with layers of crystalline vanadium oxide (mean thickness
      1.5 and 25 nm) by reactive deposition in 10(-2) mbar O2. The 1.5 nm film was
      further stabilized with a coating layer of 25 nm amorphous alumina. The so
      obtained Rh/vanadia films, containing vanadium in the V3+ and V2+ state, were
      treated in 1 bar O2 at 673 K for 1 h and thereafter reduced in 1 bar H2 at
      increased temperatures, particularly between 723 and 873 K. The structural and
      morphological changes were followed by (high-resolution) transmission electron
      microscopy and selected area diffraction. Oxidation at 673 K transforms the
      purely vanadia-supported samples into Rh/V2O5, while in the alumina-supported
      films containing only small amounts of VOx, the formation of topotactic V2O3 is
      observed. The formation of Rh-V alloys during the subsequent reduction is
      strongly determined by the intimate contact and the structural and orientational
      relationship between Rh particles and the surrounding VOx phase. Reduction above
      473 K transforms the support into substoichiometric vanadium oxides of
      composition VO and V2O. Analysis of high-resolution images and diffraction
      patterns reveals the presence of different alloy phases after reduction with
      increasing T (from 573 up to 823 K). In the alumina-supported film (low V/Rh
      ratio) the epitaxial alignment between the Rh particles and the surrounding V2O3
      phase apparently favours the primary formation of defined alloys of type V3Rh and
      VRh3, followed by VRh at higher temperature. On the contrary, mainly V3Rh5 is
      formed in the purely VOx-supported Rh/films, due to different epitaxial relations
      in the initial state. Possible pathways of alloy formation are discussed.

PMID- 16633604
TI  - The role of alpha-iron and cementite phases in the growing mechanism of carbon
      nanotubes: a 57Fe Mossbauer spectroscopy study.
AB  - 57Fe Mossbauer spectroscopy was used to study the reduction behavior at
      temperatures as high as 1073 K of an iron/silica catalyst, and also the
      carbonaceous materials isolated after acetylene decomposition over this catalyst
      at several temperatures (873-1073 K). The products were previously characterized
      by transmission electron microscopy and it was clearly proven that the
      concentration of carbon nanotubes increased when reaction reached highest
      temperatures. This was related with an increment in cementite concentration
      (generated from initial alpha-iron and the progressive reduction of the remnant
      Fe+2 caused by acetylene decomposition) as detected by 57Fe Mossbauer. These
      results undoubtedly revealed the role of alpha-iron as active center for
      acetylene decomposition and cementite as main carbide intermediate species in the
      catalytic growth of CNTs.

PMID- 16633605
TI  - Pressure perturbation calorimetric studies of the solvation properties and the
      thermal unfolding of proteins in solution--experiments and theoretical
      interpretation.
AB  - We used pressure perturbation calorimetry (PPC), a relatively new and efficient
      technique, to study the solvation and volumetric properties of amino acids and
      peptides as well as of proteins in their native and unfolded state. In PPC, the
      coefficient of thermal expansion of the partial volume of the protein is deduced
      from the heat consumed or produced after small isothermal pressure jumps, which
      strongly depends on the interaction of the protein with the solvent or cosolvent
      at the protein-solvent interface. Furthermore, the effects of various chaotropic
      and kosmotropic cosolvents on the volume and expansivity changes of proteins were
      measured over a wide concentration range with high precision. Depending on the
      type of cosolvent and its concentration, specific differences were found for the
      solvation properties and unfolding behaviour of the proteins, and the volume
      change upon unfolding may even change sign. To yield a molecular interpretation
      of the different terms contributing to the partial protein volume and its
      temperature dependence, and hence a better understanding of the PPC data,
      molecular dynamics computer simulations on SNase were also carried out and
      compared with the experimental data. The PPC studies introduced aim to obtain
      more insight into the basic thermodynamic properties of protein solvation and
      volume effects accompanying structural transformations of proteins in various
      cosolvents on one hand, as these form the basis for understanding their
      physiological functions and their use in drug designing and formulations, but
      also to initiate further valuable applications in studies of other biomolecular
      and chemical systems.

PMID- 16633606
TI  - A structural phase diagram for model aqueous organic nanodroplets.
AB  - Our density functional theory calculations predict that model aqueous organic
      nanodroplets have either well mixed or core-shell structures, depending on the
      state of the metastable binary vapor and that, furthermore, there is a broad
      transition region in the phase diagram where both structures can occur at the
      same vapor state.

PMID- 16633607
TI  - An ab initio study of the electronic structure of BCl3(2+) and its decomposition
      pathways.
AB  - Ab initio methods have been used to characterise the lowest energy potential
      energy surfaces of 1BCl3(2+) and 3BCl3(2+). The methods used are MP2, CCSD,
      CCSD(T) and MCSCF with 6-311G(d), cc-pVTZ and aug-cc-pVTZ basis sets. While the
      singlet surface is relatively straight-forward, the triplet surface is very
      complicated, with many stationary points in close energetic proximity. The
      singlet surface can fragment to the following products (1BCl + 1Cl+ + 1Cl+),
      (1Cl+ + 1B+ + 1Cl2), (2BCl+ + 2Cl), while the triplet surface can fragment to
      (1BCl2+ + 3Cl+) and (2BCl2(2+) + 2Cl). 2BCl2(2+) can further fragment to (1Cl+ +
      2BCl+). These results are in good agreement with previous experimental data from
      coincidence mass spectroscopy. [symbol: see text]1 diagnostic values have been
      calculated for all of the stationary points of BCl3(2+), using the method of Lee
      and Taylor. These data, together with CCSD/CCSD(T) energy differences and MCSCF
      calculations, are used to conclude that most of the stationary points on the
      singlet surface are well represented using single reference methods. The
      stationary points of the triplet system have [symbol: see text]1 diagnostic
      values greater than those for the singlet system, as expected when using the
      closed-shell [symbol: see text]1 diagnostic method of Lee and Taylor. However,
      all of the structures have acceptable single reference wavefunctions if the open
      shell upper limit of Rienstra-Kiracofe et al. (0.045) is used, a conclusion fully
      supported by CCSD/CCSD(T) energy differences. CCSD(T) energies determined for the
      fragmentation asymptotes have been compared with experimental data collated from
      the NIST Theoretical and Scientific Data website, and the generally very good
      agreement between theory and experiment reinforces the reliability of the CCSD(T)
      method.

PMID- 16633608
TI  - Structure, stability, electronic and magnetic properties of Ni4 clusters
      containing impurity atoms.
AB  - Using a gradient-corrected density functional method, we studied computationally
      how single impurity atoms affect the structure and the properties of a Ni4
      cluster. H and O atoms coordinate at a Ni-Ni bond, inducing small changes to the
      structure of bare Ni4 which is essentially a tetrahedron. For a C impurity, we
      found three stable structures at a Ni4 cluster. In the most stable geometry, the
      carbon atom cleaves a Ni-Ni bond of Ni4, binding to all Ni atoms. Inclusion of
      the impurity atom leads to a partial oxidation of the metal atoms and, in the
      most stable structures, reduces the spin polarization of the cluster compared to
      bare Ni4. An H impurity interacts mainly with the Ni 4s orbitals, whereas the Ni
      3d orbitals participate strongly in the bonding with O and C impurity atoms. For
      these impurity atoms, Ni 3d contributions dominate the character of the HOMO of
      the ligated cluster, in contrast to the HOMO of bare Ni4 where Ni 4s orbitals
      prevail. We also discuss a simple model which relates the effect of a H impurity
      on the magnetic state of metal clusters to the spin character (minority or
      majority) of the LUMO or HOMO of the bare metal cluster.

PMID- 16633609
TI  - S3O2--an unusual structure with pi*-pi* interaction.
AB  - The structures and relative stabilities of 15 S3O2 isomers have been investigated
      by G3X(MP2), CCSD(T)/aug-cc-pVTZ and MRCI/CASSCF calculations. The global energy
      minimum is a three-membered sulfur ring with two adjacent sulfoxide groups in a
      trans conformation, i.e. a vic-disulfoxide of C2 symmetry. The SS bond lengths
      are 2.136 (2x) and 2.354 angstroms at the CCSD(T)/cc-pVTZ level of theory. There
      is a strong interaction between the pi* orbitals of the two S=O moieties both in
      the trans and in the almost degenerate cis conformer. The corresponding chain
      like singlet and triplet isomers of connectivity OSSSO lie close in energy (ca.
      67 kJ mol(-1)) while five-membered and branched four-membered rings are
      significantly less stable. The structure of S3O2 is in contrast to that of the
      isoelectronic analogue S5, which exists as a five-membered twisted heterocycle.

PMID- 16633610
TI  - Photophysics and spectroscopy of the higher electronic states of zinc
      metalloporphyrins: a theoretical and experimental study.
AB  - The photophysics of the S2 and S1 excited states of zinc porphyrin (ZnP) and five
      of its derivatives (ZnOEP, ZnTBP, ZnTPP, ZnTFPP, ZnTCl8PP) have been investigated
      by measuring their steady-state absorption and fluorescence spectra, quantum
      yields and excited state lifetimes at room temperature in several solvents. The
      radiative and radiationless decay constants of the fluorescent excited states
      accessible in the visible and near UV regions of the spectrum have been obtained.
      Despite the similarities in the Soret spectra of these compounds, their S2
      excited state radiationless decay rates differ markedly. Although the S2-S1
      electronic energies of a given zinc porphyrin vary linearly with the Lippert
      (refractive index) function of the solvent, the S2 radiationless decay rates of
      the set of compounds do not follow the energy gap law of radiationless transition
      theory. Calculations, using time-dependent density functional theory (TDDFT), of
      the energies and symmetries of the complete set of excited states accessible by 1
      or 2-photon absorption in the near UV-visible have also been carried out.
      Substitution on the porphyrin macrocycle framework affects the ground state
      geometry and alters the electron density distributions, the orbital energies and
      the relative order of the excited electronic states accessible in the near UV
      blue regions of the spectrum. The results are used to help interpret both the
      nature of the electronic transitions in the Soret region, and the relative
      magnitudes of the radiationless transition rates of the excited states involved.

PMID- 16633611
TI  - Generalised Maxwell-Garnett equation: application to electrical and chemical
      transport.
AB  - In this paper we discuss the implementation of different equilibrium
      concentrations in each of the phases into the Maxwell-Garnett effective medium
      formula for diffusion in heterogeneous media. We put the derivation given by
      Kalnin et al., J. Phys. Chem. Solids, 2002, 63, 449, on safer grounds and extend
      it to non-dilute carrier concentrations. The relation to Maxwell's mixing rule is
      also elaborated. It is shown that the formula can not only successfully be
      applied to conductivity problems but also to describe steady state chemical
      diffusion in heterogeneous media such as polycrystalline samples. The comparison
      with the brick layer model corroborates these points but also shows that-in the
      case of heterogeneous media-one has to be cautious in applying steady state
      results to transient kinetics.

PMID- 16633612
TI  - Hole burning spectroscopy of ribonuclease A.
AB  - We present pressure tuning hole burning experiments with the enzyme ribonuclease
      A using the UV-absorbing amino acid tyrosine as a probe. We show that, at 2 K,
      the protein is intact, and that at least four different regions which we
      associate with different tyrosine sites can be distinguished through their
      specific response to pressure. For one site we could determine the
      compressibility to 0.15 GPa(-1). Upon denaturing the protein with guanidine
      hydrochloride, one of the tyrosine sites is preserved to a large extent. Reducing
      the sulfur bonds has a more drastic effect: the tyrosine sites lose most of their
      individual features and their compressibilities come close to that of tyrosine in
      solution.

PMID- 16633613
TI  - Determination of geometric orientation of adsorbed cinchonidine on Pt and Fe and
      quiphos on Pt nanoclusters via DRIFTS.
AB  - Platinum nanoclusters modified with cinchonidine have been employed as 'quasi
      homogeneous' catalysts for the hydrogenation of ethyl pyruvate and have
      demonstrated exceptional activities while the ee's of these systems are currently
      inferior to the traditional Pt/Al2O3 heterogeneous system. For the bulk systems
      it has been shown that the orientation of the modifier on the metal surface is a
      critical parameter influencing catalytically induced enantioselectivity. It has
      been speculated that the lower observed ee's for the nanocluster systems are a
      result of the modifier assuming an orientation unfavorable for inducing
      enantioselectivity due to the lack of large numbers of planar metal atoms. Using
      DRIFTS (diffuse reflectance infra-red Fourier transform spectroscopy) analysis of
      samples together with geometry optimization and IR modelling we have studied the
      orientation of cinchonidine on Pt and Fe nanoclusters and additionally the man
      made ligand quiphos on Pt nanoclusters. It has been determined that cinchonidine
      can adsorb on Pt and Fe nanoclusters in both 'flat' and 'tilted' modes, while
      quiphos can be adsorbed on Pt only via the 'pi-bonded' mode. These studies thus
      provide an insight into modifier orientation on nanocluster surfaces that can be
      extended to a wide range of potential modifiers and facilitate a better
      understanding of the origin of enantioselectivity with these 'quasi-homogeneous'
      catalyst systems.

PMID- 16633614
TI  - Role of dopant concentration and surface coating on photophysical properties of
      CdS: Eu3+ nanocrystals.
AB  - Here, we report the role of dopant concentration and surface coating of CdS: Eu3+
      nanocrystals on the modification of crystal structure and their photoluminescence
      properties by steady-state and time resolved fluorescence studies. It is found
      that photoluminescence properties are sensitive to the crystal structure which is
      controlled by surface coating and dopant concentration. The emission intensity of
      the peak at 614 nm (5D0 --> 7F2) of the Eu3+-ions is found to be sensitive to the
      doping and surface coating of CdS nanocrystals. It is found that the average
      decay times tau are 248, 353 and 499 micros for 0.25, 0.5 and 1.0 mol% Eu ions
      doped into CdS nanocrystals, respectively. From the decay time measurements, it
      is evident that the energy transfer occurs from CdS nanoparticles to Eu3+ ions
      and the calculated energy transfer efficiency from CdS nanoparticles to Eu3+ ions
      is 9.2 and 35% for Eu3+ ions coated and doped CdS nanoparticles, respectively.
      Our analysis suggests that site symmetry of ions plays a very important role in
      the modifications of radiative and nonradiative relaxation mechanisms.

PMID- 16633615
TI  - In situ observation of homogeneous nucleation of nanosized zeolite A.
AB  - The formation of zeolite A (LTA) in the presence of tetramethylammonium cations
      is studied using in situ small angle and wide angle X-ray scattering (SAXS/WAXS)
      techniques. The SAXS measurements show the formation of homogeneous precursors 10
      nm in size prior to the crystallization of LTA which were consumed during the
      crystallization. The crystal size is estimated by fitting the SAXS patterns with
      an equation for a cubic particle, and it is revealed that the final crystal size
      of the LTA depends on the synthesis temperature. However, although such
      temperature dependence is noted for the final crystal size, the initial precursor
      particles size appears to be closely similar (ca. 10 nm) irrespective of the
      synthesis temperature.

PMID- 16633616
TI  - Remarks on catalytic reduction of CO2, H+ and H2 by monovalent Ni.
AB  - Prompted by catalysis of CO2 electroreduction by a tetraazamacrocyclic
      Ni(i)(cyclam) complex (cyclam = 1,4,8,11-tetraazacyclotetradecane), we examine
      theoretically the possibility of H2 reduction by this molecule. We show that the
      process 2 Ni(i) + H2 --> 2 [Ni(ii)(H-)] is thermodynamically facile, and that H2
      could be reduced by a binuclear Ni(i) complex in two concerted 1e- processes. Our
      calculations also indicate that hydride complexes of Ni(iii)(cyclam) are
      significantly unstable thermodynamically and therefore they are unlikely to serve
      as intermediates in process of H2 evolution from water.

PMID- 16633617
TI  - Computational studies of molecular hydrogen binding affinities: the role of
      dispersion forces, electrostatics, and orbital interactions.
AB  - Intermolecular interactions between H2 and ligands, metals, and metal-ligand
      complexes determine the binding affinities of potential hydrogen storage
      materials (HSM), and thus their extent of potential for practical use. A brief
      survey of current activity on HSM is given. The key issue of binding strengths is
      examined from a basic perspective by surveying the distinct classes of
      interactions (dispersion, electrostatics, orbital interactions) in first a
      general way, and then in the context of calculated binding affinities for a range
      of model systems.

PMID- 16633618
TI  - Chemical failure modes of AlQ3-based OLEDs: AlQ3 hydrolysis.
AB  - Tris(8-hydroxyquinoline)aluminum(III), AlQ3, is used in organic light-emitting
      diodes (OLEDs) as an electron-transport material and emitting layer. The reaction
      of AlQ3 with trace H2O has been implicated as a major failure pathway for AlQ3
      based OLEDs. Hybrid density functional calculations have been carried out to
      characterize the hydrolysis of AlQ3. The thermochemical and atomistic details for
      this important reaction are reported for both the neutral and oxidized AlQ3/AlQ3+
      systems. In support of experimental conclusions, the neutral hydrolysis reaction
      pathway is found to be a thermally activated process, having a classical barrier
      height of 24.2 kcal mol(-1). First-principles infrared and electronic absorption
      spectra are compared to further characterize AlQ3 and the hydrolysis pathway
      product, AlQ2OH. The activation energy for the cationic AlQ3 hydrolysis pathway
      is found to be 8.5 kcal mol(-1) lower than for the neutral reaction, which is
      significant since it suggests a role for charge imbalance in promoting chemical
      failure modes in OLED devices.

PMID- 16633619
TI  - Exactly solvable approximating models for Rabi Hamiltonian dynamics.
AB  - The interaction between an atom and a one mode external driving field is an
      ubiquitous problem in many branches of physics and is often modeled using the
      Rabi Hamiltonian. In this paper we present a series of analytically solvable
      Hamiltonians that approximate the Rabi Hamiltonian and compare our results to the
      Jaynes-Cummings model which neglects the so-called counter-rotating term in the
      Rabi Hamiltonian. Through a unitary transformation that diagonalizes the Jaynes
      Cummings model, we transform the counter-rotating term into separate terms
      representing several different physical processes. By keeping only certain terms,
      we can achieve an excellent approximation to the exact dynamics within specified
      parameter ranges.

PMID- 16633621
TI  - Molecular dynamics and ordering of pyridine in its cyclophosphazene inclusion
      compound as evaluated by solid state 2H NMR spectroscopy.
AB  - Variable temperature 2H NMR experiments (line shape analysis, relaxation studies)
      were carried out on the pyridine-d5-tris-(1,2-dioxyphenyl)-cyclotriphosphazene
      inclusion compound in the temperature range between 110-300 K. It is found that
      the pyridine guests are highly mobile throughout the whole temperature range
      covered here. The observation of three superimposed 2H NMR signals can be
      understood in terms of a particular (motionally averaged) orientation of the
      pyridine molecules, which is a consequence of the molecular symmetry of the
      pyridine guests and the imposed channel restrictions. The experimental data are
      consistent with a combined rotation on cone-small angle fluctuation model, which
      assumes a fast molecular reorientation between two superimposed cones with an
      opening angle for the inner cone between 59-73 degrees (angle of fluctuation
      between 1-3 degrees ). On the basis of this model assumption it is possible to
      reproduce both the experimental 2H NMR line shapes and the spin-lattice
      relaxation data in a quantitative way. The analysis of the partially relaxed
      spectra (inversion recovery experiments) yields the correlation times for this
      overall motional process. They follow an Arrhenius behavior from which an
      activation energy of 8.7 +/- 0.4 kJ mol(-1) is derived. The results are discussed
      in the framework of the published data for related systems.

PMID- 16633620
TI  - Theoretical modeling of the valence UV spectra of 1,2,3-triazine and uracil in
      solution.
AB  - Assessment of the perturbed matrix method (PMM) ability in reproducing valence UV
      absorption spectra is carried out on two model systems: 1,2,3-triazine in
      methanol solution and uracil in water solution. Results show that even using the
      simplest definition of the quantum center, i.e. the portion of the system
      explicitly treated quantum mechanically, PMM provides rather good results. This
      paper further confirms the possibility of using PMM as a theoretical
      computational tool, complementary to other methodologies, for addressing the
      electronic properties in molecular systems of high complexity.

PMID- 16633622
TI  - Ab initio and RRKM study of photodissociation of azulene cation.
AB  - The ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) approach has been applied to
      investigate the photodissociation mechanism of the azulene cation at different
      values of the photon energy. Reaction pathways leading to various decomposition
      products have been mapped out at the G3(MP2,CC)//B3LYP level and then the RRKM
      and microcanonical variational transition state theories have been applied to
      compute rate constants for individual reaction steps. Relative product yields
      (branching ratios) for the dissociation products have been calculated using the
      steady-state approach. The results show that a photoexcited azulene cation can
      readily isomerize to a naphthalene cation. The major dissociation channels are
      elimination of atomic hydrogen, an H2 molecule, and acetylene. The branching
      ratio of the H elimination channel decreases with an increase of the photon
      energy. The branching ratio of the acetylene elimination as well as that of the
      H2 elimination rise as the photon energy increases. The main C8H6+ fragment at
      all photon energies considered is a pentalene cation, and its yield decreases
      slightly with increasing excitation energy, whereas the branching ratios of the
      other C8H6+ fragments, phenylacetylene and benzocyclobutadiene cations, grow.

PMID- 16633623
TI  - Kinetics of the reactions of CH2Br and CH2I radicals with molecular oxygen at
      atmospheric temperatures.
AB  - The kinetics of the reactions of CH2Br and CH2I radicals with O2 have been
      studied in direct measurements using a tubular flow reactor coupled to a
      photoionization mass spectrometer. The radicals have been homogeneously generated
      by pulsed laser photolysis of appropriate precursors at 193 or 248 nm. Decays of
      radical concentrations have been monitored in time-resolved measurements to
      obtain the reaction rate coefficients under pseudo-first-order conditions with
      the amount of O2 being in large excess over radical concentrations. No buffer gas
      density dependence was observed for the CH2I + O2 reaction in the range 0.2-15 x
      10(17) cm(-3) of He at 298 K. In this same density range the CH2Br + O2 reaction
      was obtained to be in the third-body and fall-off area. Measured bimolecular rate
      coefficient of the CH2I + O2 reaction is found to depend on temperature as k(CH2I
      + O2)=(1.39 +/- 0.01)x 10(-12)(T/300 K)(-1.55 +/- 0.06) cm3 s(-1)(220-450 K).
      Obtained primary products of this reaction are I atom and IO radical and the
      yield of I-atom is significant. The rate coefficient and temperature dependence
      of the CH2Br + O2 reaction in the third-body region is k(CH2Br + O2+ He)=(1.2 +/-
      0.2)x 10(-30)(T/300 K)(-4.8 +/- 0.3) cm6 s(-1)(241-363 K), which was obtained by
      fitting the complete data set simultaneously to a Troe expression with the
      F(cent) value of 0.4. Estimated overall uncertainties in the measured reaction
      rate coefficients are about +/-25%.

PMID- 16633624
TI  - An elegant method to study an isolated spiral wave in a thin layer of a batch
      Belousov-Zhabotinsky reaction under oxygen-free conditions.
AB  - A method to prepare a uniform thin layer of a batch Belousov-Zhabotinsky (BZ)
      reaction under oxygen-free conditions for the study of an isolated spiral wave is
      presented. After a first layer of gel soaked with the BZ solution has been
      delivered into the reactor, a single spiral wave was initiated, and finally the
      remaining reactor volume was filled with gel and BZ medium. The completely filled
      reactor is sealed gas-tightly, yielding oxygen-free, and thus more controlled,
      reaction conditions. A systematic study of the behaviour of an isolated spiral
      wave in a ferroin-catalyzed BZ reaction under batch conditions has been
      performed. Recipes for BZ media that support a slowly rotating meandering spiral
      were developed. In cases of extremely low excitability (i.e., relative large
      stimuli are required to induce a propagating wave), the number of petals in the
      trajectory of a spiral tip decreased due to aging of the reaction system. Since
      oxygen-free conditions are necessary for the study of the dynamics in three
      dimensional excitable media, and the wave velocities of a spiral are sufficiently
      low, the developed chemical recipes are suitable for studies of the behaviour of
      scroll waves in three-dimensional systems by optical tomography.

PMID- 16633625
TI  - Plasmon interactions between gold nanoparticles in aqueous solution with
      controlled spatial separation.
AB  - The effects of interparticle distance on the UV-visible absorption spectrum of
      gold nanocrystals aggregates in aqueous solution have been investigated. The
      aggregates were produced by ion-templated chelation of omega-mercaptocarboxylic
      acid ligands covalently attached to the nanoparticles surface. Variation of the
      ligand chain length provides control over the interparticle separation in the
      aggregates. The UV-visible spectra consist typically of a single particle band
      and a secondary band at higher wavelengths associated with the formation of
      aggregates in solution. The position of the latter depends on interparticle
      separation up to distances of approximately 8 nm, in accordance with existing
      models. Potential applications therefore include distance sensitive labels or
      proximity probes. Conversely, variation of the ligand length allows the
      preparation of nanostuctured materials with tuned optical properties.

PMID- 16633626
TI  - Comparative study of cluster- and supercell-approaches for investigating
      heterogeneous catalysis by electronic structure methods: tunneling in the
      reaction N + H --> NH on Ru(0001).
AB  - Different ruthenium clusters of various sizes are constructed with the aim to
      model the Ru(0001) surface with a sufficient accuracy for predicting catalysis by
      hybrid density functional methods (B3LYP). As an example reaction the
      hydrogenation step N(ads) + H(ads) --> NH(ads) from the catalytic production
      cycle of ammonia is chosen. A cluster of 12 ruthenium atoms is found to reproduce
      experimental geometries and frequencies of the various reactants on the surface
      satisfyingly. To get the geometries of adsorbed hydrogen qualitatively correct it
      is shown that second layer atoms have to be included in the model cluster.
      Boundary effects are believed to have minor effects on optimized geometries,
      whereas the effects on reaction barriers are significant. A comparison of model
      cluster calculations to a periodic supercell approach employing plane waves and
      density functional methods (RPBE) reveals similar barriers for reaction. The
      influence of tunneling in this reaction is determined by the small curvature
      tunneling approach on the electronic surfaces.

PMID- 16633627
TI  - Photo-induced transformations in 2,2':5',2''-terthiophene thin films on silver.
AB  - We report on transient photo-induced structural changes of 2,2':5',2''
      terthiophene (3T) adsorbed on silver nanoparticles. Surface-enhanced Raman
      scattering (SERS) data show that the film thickness predetermines the eventual
      course of these changes. In particular, for high molecular concentrations (thick
      adsorbate layers), illumination leads to a photoinduced polymerization of the 3T
      film. For thin layers ( approximately monolayer coverage), the photoinduced
      spectral evolution is qualitatively different. We interpret the latter process as
      a cleavage of the terthiophene molecule, resulting in isolated thiophene units.
      Calculations of excitation energies for 3T + 3Ag+ and 1T + Ag+ revealed visible
      transitions, while calculated Raman frequencies indicated 1T as a possible
      photoproduct. As no photoinduced transformations are observed for 3T in the solid
      or solution phases, it is likely that the processes reported here originate in
      surface-enhanced charge-transfer between the Ag-surface and the organic
      adsorbate.

PMID- 16633628
TI  - Application of time- and space-resolved fluorescence spectroscopy to the
      distribution of guest species into micrometer-sized zeolite crystals.
AB  - We measured the fluorescence decays and spectra of perylene adsorbed from
      solution into zeolite X crystals of 2-3 microm in diameter at the level of
      individual crystals by the application of a microscopy method coupled with a
      single photon counting apparatus and a multichannel spectrophotometer. We found
      that both decays and spectra are particle-dependent, i.e. a particle-to-particle
      difference was observed for the fluorescence decay curves at a fixed loading
      level along with a particle-dependent spectral change due to the various
      contribution of excimer emission band relative to those of three monomers. These
      findings are due to a non-homogeneous distribution which is confirmed by the
      various emission intensities of perylene-loaded zeolite crystals observed by
      fluorescence microscopy. Previously, a homogeneous distribution of the guest
      between zeolite crystals has been just taken for granted and not justified by
      experiment. The present result suggests that commonly employed collective
      measurements such as UV-VIS absorption and emission spectroscopies, IR and Raman
      spectroscopies, and NMR of bulk zeolite powders provide only averaged results and
      may sometimes suffer from acquiring precise molecular level pictures.

PMID- 16633629
TI  - Chemical processes at oxide surfaces.

PMID- 16633630
TI  - Adsorption of atomic hydrogen on ZnO(1010): STM study.
AB  - The adsorption of atomic hydrogen on a single crystal ZnO(1010) surface has been
      studied by scanning tunneling microscopy (STM) under ultrahigh vacuum conditions
      at room temperature and at elevated temperatures. High resolution STM images
      indicate that a well-ordered (1x1) H adlayer is formed on the ZnO(1010) surface.
      The STM data strongly indicate that the hydrogen adsorbs on top of the oxygen
      atoms forming hydroxyl species. Scanning tunneling spectroscopy (STS) studies
      reveal a H atom induced metallization at room temperature. In contrast to the
      clean surface for the hydrogen-covered surface distinct defects structures
      consisting of missing O and Zn atoms could be identified.

PMID- 16633631
TI  - Ab initio cluster calculations on the electronic structure of oxygen vacancies at
      the polar ZnO(0001) surface and on the adsorption of H2, CO, and CO2 at these
      sites.
AB  - Oxygen vacancies at the polar O terminated (0001) surface of ZnO are of
      particular interest, because they are discussed as active sites in the methanol
      synthesis. In general, the polar ZnO surfaces are stabilized by OH groups,
      therefore O vacancies can be generated by removing either O atoms or OH or H2O
      groups from the surface. These defects differ in the number of electrons in the
      vacancy and the number of OH groups in the neighborhood. In the present study,
      the electronic structure and the adsorption properties of four different types of
      oxygen vacancies have been investigated by means of embedded cluster
      calculations. We performed ab initio calculations on F+ like surface excitations
      for the different defect types and found that the transition energies are above
      the optical band-gap, while F+ centers in bulk ZnO show a characteristic optical
      excitation at 3.19 eV. Furthermore, we studied the adsorption of CO2 and CO at
      the different defect sites by DFT calculations. We found that CO2 dissociates at
      electron rich vacancies into CO and an O atom which remains in the vacancy. At
      the OH vacancy which contains an unpaired electron CO2 adsorbed in the form of
      CO2-, while it adsorbed as a linear neutral molecule at the H2O defect. CO
      adsorbed preferentially at the H2O defect and the OH defect, both with a binding
      energy of 0.3 eV.

PMID- 16633632
TI  - Ab initio calculations of the O1s XPS spectra of ZnO and Zn oxo compounds.
AB  - O1s core level binding energies of oxygen atoms in bulk ZnO, at different ZnO
      surfaces, and in some Zn oxo compounds were calculated by means of wave function
      based quantum chemical ab initio methods. Initial and final state effects were
      obtained by Koopmans' theorem and at the DeltaSCF level, respectively. After
      correction for scalar relativistic effects and electron correlation, the
      calculated XPS peak positions are in excellent agreement with the available
      experimental data for all systems included in the present study. The O1s core
      level shifts between an isolated H2O molecule and the Zn oxo compounds or ZnO, as
      well as between oxygen atoms in bulk ZnO and at various ZnO surfaces, can be
      understood by means of Madelung potentials and electronic relaxation or
      screening. XPS spectra were calculated for various cluster models which are
      designed to describe different possibilities of stabilizing the polar O
      terminated ZnO(0001) surface by the adsorption of H atoms. The experimental
      spectra are only compatible with the theoretical results for the fully
      hydroxylated H-ZnO(0001) surface exhibiting a (1x1) surface structure.

PMID- 16633633
TI  - Structure and dynamics of CO overlayers on a hydroxylated metal oxide: the polar
      ZnO(0001) surface.
AB  - The adsorption and desorption of CO on the hydroxylated, O-terminated polar
      ZnO(0001) surface has been studied using He-atom scattering. The experimental
      results reveal the formation of a physisorbed ordered CO overlayer. In addition
      to recording angular distributions of elastically scattered He atoms, also the
      dynamical properties of the CO overlayer have been investigated using inelastic
      He-atom scattering. With the aid of electronic structure calculations a loss peak
      with an energy transfer of 7.2 meV is assigned to the frustrated translation of
      the CO molecule normal to the surface.

PMID- 16633634
TI  - Water adsorption on the hydroxylated H-(1x1) O-ZnO(0001) surface.
AB  - The adsorption of water multilayers on a well defined single crystal, hydroxyl
      terminated ZnO-surface, H(1x1)-O-ZnO(0001) surface has been investigated using
      infrared (IR) spectroscopy, helium atom scattering (HAS) and X-ray photoelectron
      spectroscopy (XPS). The results reveal the formation of well ordered mono-, bi-
      and multilayers of D2O and H2O on this substrate. On the bare hydroxyl-covered
      H(1x1) surface the OH-stretch vibration could be clearly identified in the IR
      spectra. The water adsorption and desorption kinetics on this hydroxylated
      surface were studied by monitoring the reflectivity of the surface for helium
      atoms. The analysis of the data yielded activation energies for desorption of H2O
      from the H(1x1) O-ZnO surface of 55.2 kJ mol-1. The results reveal the formation
      of ordered mono- and bilayers. Further exposure to water at 113 K results in the
      formation of amorphous 3-D islands.

PMID- 16633635
TI  - Water adsorption on ZnO(1010): from single molecules to partially dissociated
      monolayers.
AB  - Static and dynamic density functional calculations have been used to study the
      structure and energetics of water adsorbed on the main cleavage plane of ZnO. In
      the single molecule limit we find that molecular adsorption is strongly
      preferred. The water binding energy increases for higher coverages due to an
      almost isotropic attractive water-water interaction which leads to clustering and
      formation of monolayer islands in the low water coverage regime. A thermodynamic
      analysis further shows that the full water monolayer is clearly the most stable
      phase until water starts to desorb. The water monolayer is even more stabilized
      by a partial dissociation of the water molecules, yielding as most stable
      configuration a (2x1) superstructure where every second water molecule is
      cleaved. The dissociation barrier for this process is very small which allows for
      an auto-dissociation of the water molecules even at low temperatures as observed
      experimentally. Finally we find that the energy cost involved to form [1210]
      oriented domain boundaries between (2x1) patches with different orientation is
      almost negligible which explains the abundance of such domain boundaries in STM
      images.

PMID- 16633636
TI  - Spectroscopic evidence for the partial dissociation of H2O on ZnO(1010).
AB  - The interaction of water with the non-polar ZnO(1010) surface has been studied by
      high resolution electron energy loss spectroscopy (HREELS) and thermal desorption
      spectroscopy (TDS). Adsorption of water at room temperature leads to the partial
      dissociation of water molecules giving rise to a well defined (2x1)
      superstructure. This observation was confirmed by the HREELS data which show the
      water-induced O-H stretching modes at 396 and 460 meV (3193 and 3709 cm-1) as
      well as the peak at 456 meV (3677 cm-1) arising from the OH species. The large
      red shift of the loss at 396 meV indicates unusually strong hydrogen bonding
      interactions of water to both neighbouring adsorbate molecules and the surface O
      atoms which are responsible for the partial dissociation of water molecules on
      the perfect ZnO(1010) surface.

PMID- 16633638
TI  - The reduction of copper in porous matrices--the role of electrostatic
      stabilisation.
AB  - The redox properties of Cu(II) species in FAU matrices have been studied by
      temperature programmed reduction (TPR) in hydrogen and by XAFS analysis of the
      products obtained after (stationary) reduction treatments at various
      temperatures. The influence of the matrix polarity was investigated by comparing
      aluminosilicate FAU (Y zeolite) with siliceous FAU. In addition, the influence of
      Zn ions on the reduction process was studied. It was found that both the matrix
      composition and the presence of zinc ions exert a significant influence on the
      course of the reduction. In Y zeolite, heat treatment which is known to transfer
      Cu(II) ions to remote sites (SI, SI', SII') affects the reduction process
      dramatically. Cu(II) is most easily reduced in siliceous FAU, but the reduction
      proceeds in two clearly separated steps. Between these steps, small Cu(0) nuclei
      coexist with Cu(I) species, apparently unable to activate hydrogen for the
      autocatalytic reduction of the remaining Cu ions. The polarity of the matrix
      causes an upshift of the Cu(II) reduction temperature (in TPR by ca. 80 K for
      sites in the large cavity, by ca. 105 K for the remote sites), but the reduction
      of Cu(I) depends strongly on the simultaneous presence of Cu(0) and on its
      ability to activate hydrogen and induce an autocatalytic reduction mechanism.
      While Cu(I) species in the large cavities are easily reduced to the metal,
      tending to segregate from the zeolite lattice, Cu(I) ions in remote sites are
      strongly stabilized towards further reduction and even traces of Cu metal form
      only at very high temperatures. In the presence of zinc ions, the Cu metal
      particles formed were found to be smaller than in zinc-free samples.

PMID- 16633637
TI  - The influence of strongly reducing conditions on strong metal-support
      interactions in Cu/ZnO catalysts used for methanol synthesis.
AB  - A systematic series of binary and ternary copper catalysts was investigated using
      the methanol synthesis reaction at atmospheric pressure. Strong metal-support
      interactions between copper and zinc oxide induced by strongly reducing
      conditions were probed by the adsorption of carbon monoxide, which was monitored
      qualitatively and quantitatively by a combination of microcalorimetry,
      temperature-programmed desorption experiments and Fourier transform infrared
      spectroscopy. For the zinc oxide-containing catalysts, the pretreatment in
      flowing carbon monoxide at 493 K resulted in a severe decoration of the copper
      metal particles with ZnOx adspecies, whereas after methanol synthesis at 493 K
      the state of the copper was essentially identical to that seen after hydrogen
      reduction. Copper was always found to be present in its zero-valent state.

PMID- 16633639
TI  - Selective photo-deposition of Cu onto the surface of monodisperse oleic acid
      capped TiO2 nanorods probed by FT-IR CO-adsorption studies.
AB  - A novel, non-aqueous, organometallic route to nanocomposite Cu@TiO2 materials is
      presented. TiO2 nanorods stabilized with oleic acid (OLA) were used as support
      for the photo-assisted deposition of Cu using the organometallic Cu(II) precursor
      [Cu(OCH(CH3)CH2N(CH3)2)2] (1). The copper precursor penetrates through the shell
      of OLA and is photo reduced to deposit Cu0 directly at the surface of the TiO2
      rods. The obtained Cu decorated nanorods were still soluble in nonpolar organic
      solvents without change of the morphology of nanorods. The Cu@TiO2 colloid was
      characterized by means of UV-VIS, XRD, AAS, and HRTEM. FTIR CO adsorption studies
      provide evidence for Cu0 anchored at the titania surface by a characteristic
      absorption at 2084 cm-1. Comparative studies of Cu-deposition were performed
      using CuCl2 as simple Cu source which proved that the concept of organometallic
      disguise of the metal centre results in a higher reaction rate and the
      circumvention of non-selective reduction, parasitic side reactions and undesired
      agglomeration of the OLA stabilized titania nanorods.

PMID- 16633641
TI  - Structure and activity of oxidized Pt(110) and alpha-PtO2.
AB  - We present a density functional theory study of the structure and reactivity of
      Pt(110) under high loads of atomic oxygen. Surface structures in which the oxygen
      adsorbs on PtO2-like stripes along the Pt ridges of the Pt(110) are found to be
      highly stable. The structures become further stabilized when Pt atoms are ejected
      from the Pt ridges since this allows for stress relief along the PtO2 stripes.
      Our results thus corroborate the Pt(110)-(12x2)-22O surface oxide structure
      proposed by Li et al. [Phys. Rev. Lett., 2004, 93, 146104]. We further considered
      the structure and stability of bulk alpha-PtO2 oxide surfaces. The (0001) and
      (1010) facets are found to be the lowest energy facets. Finally, the reactivity
      of the surface oxide and the oxide surfaces in terms of CO oxidation was
      investigated. We find small energy barriers for the reaction at the Pt(110)
      (12x2)-22O surface oxide and at the (1010) facet of alpha-PtO2, but only large
      barriers over the alpha-PtO2(0001) surface.

PMID- 16633640
TI  - Microkinetic modeling of CO TPD spectra using coverage dependent
      microcalorimetric heats of adsorption.
AB  - CO adsorption on the ternary methanol synthesis Cu/ZnO/Al2O3 catalyst was studied
      in detail by means of adsorption microcalorimetry and flow temperature-programmed
      desorption (TPD). Based on these experimental data, we established a microkinetic
      analysis method, which provides information about the adsorption kinetics of CO
      on the catalyst surface. Experimentally derived microcalorimetric heats of
      adsorption were applied in a microkinetic model to simulate TPD curves with
      varying initial coverage. Two approaches were used: an integral approach based on
      evaluation of the integral heats of adsorption which predicts the experimental
      TPD curves roughly and provides first approximations for the preexponential
      factors. The second, more detailed approach was based on the simulation of the
      adsorption isotherm taking the experimentally determined coverage-dependence of
      the heat of adsorption into account. This approach led to a significantly
      improved agreement between experimental and simulated TPD curves. Moreover, it
      was possible to derive the standard entropy of adsorption. The general
      applicability of our approaches is demonstrated by analyzing the CO TPD and
      microcalorimetry data obtained with a binary ZnO-free Cu/Al2O3 catalyst.

PMID- 16633642
TI  - Pressure-dependent Ni-O phase transitions and Ni oxide formation on Pt(111): an
      in situ STM study at elevated temperatures.
AB  - Growth, atomic structure and O2 partial pressure dependent phase transitions of
      Ni-O structures and thin NiO films on Pt(111) have been studied using scanning
      tunnelling microscopy (STM), low-energy electron diffraction (LEED), and Auger
      electron spectroscopy (AES). In situ STM experiments were performed during film
      growth by reactive metal deposition at elevated temperatures (400-550 K) and
      variable O2 pressure. Depending on the substrate temperature, one-dimensional
      network-like Ni-O structures and islands with (7x1) and (4x2) reconstructions are
      formed during the initial stages of growth. These structures transform reversibly
      to a (2x2) reconstruction in a narrow O2 pressure range of 1.5-2x10(-6) mbar and
      can be monitored by in situ STM. Upon reduction of the O2 pressure to <10(-10)
      mbar pseudomorphic Ni monolayers are obtained. The defect-free ordering of Ni
      atoms on Pt(111) in a single stacking domain indicates an O-surfactant induced
      growth mode. The structural properties of the O2 pressure-dependent Ni-O phases
      are discussed in a simple model assuming NiO(001)-like atomic arrangements in the
      adsorbate overlayer. At higher coverage stable (111)-oriented NiO islands grow in
      a three-dimensional mode.

PMID- 16633643
TI  - Photo-induced desorption of NO from NiO(100): calculation of the four-dimensional
      potential energy surfaces and systematic wave packet studies.
AB  - The velocity distributions of the laser-induced desorption of NO molecules from
      an epitaxially grown film of NiO(100) on Ni(100) have been studied [Mull et al.,
      J. Chem. Phys., 1992, 96, 7108]. A pronounced bimodality of velocity
      distributions has been found, where the NO molecules desorbing with higher
      velocities exhibit a coupling to the rotational quantum states J. In this article
      we present simulations of state resolved velocity distributions on a full ab
      initio level. As a basis for this quantum mechanical treatment a 4D potential
      energy surface (PES) was constructed for the electronic ground and a
      representative excited state, using a NiO5Mg(18+)13 cluster. The PESs of the
      electronic ground and an excited state were calculated at the CASPT2 and the
      configuration interaction (CI) level of theory, respectively. Multi-dimensional
      quantum wave packet simulations on these two surfaces were performed for
      different sets of degrees of freedom. Our key finding is that at least a 3D wave
      packet simulation, in which the desorption coordinate Z, polar angle theta and
      lateral coordinate X are included, is necessary to allow the simulation of
      experimental velocity distributions. Analysis of the wave packet dynamics
      demonstrates that essentially the lateral coordinate, which was neglected in
      previous studies [Kluner et al., Phys. Rev. Lett. 1998, 80, 5208], is responsible
      for the experimentally observed bimodality. An extensive analysis shows that the
      bimodality is due to a bifurcation of the wave packet on the excited state PES,
      where the motion of the molecule parallel to the surface plays a decisive role.

PMID- 16633644
TI  - Interaction of SO3 with c-ZrO2(111) films on Pt(111).
AB  - Single-crystalline sulfated c-ZrO2(111) films of the cubic (c) type have been
      prepared by reactive deposition of Zr onto Pt(111) in an O2 atmosphere and
      subsequent exposition to a SO3 atmosphere. The morphology, atomic structure, and
      composition have been examined by scanning tunneling microscopy, low-energy
      electron diffraction (LEED), Auger electron spectroscopy, and density functional
      theory (DFT) calculations. The clean c-ZrO2(111) films display a (2x2) surface
      structure. During SO3 exposure at room temperature, a clear
      (radical3xradical3)R30 degrees structure develops. At about 700 K, the SO3
      induced (radical3xradical3)R30 degrees structure disappears and the bright (2x2)
      LEED pattern of the clean ZrO2 films reappears. The energies of plausible c
      ZrO2(111)/SO3 structures have been examined by DFT. The (radical3xradical3)R30
      degrees structure found in the experiments turned out to be the most stable one
      for temperatures below 700 K. At temperatures around 700 K, a disordered low
      coverage structure may exist, which can not be observed by conventional LEED. A
      comparison of cubic zirconia surfaces with the alternative tetragonal system
      yields similar results for the SO3 adsorption in the DFT calculations and shows
      that c-ZrO2 surfaces are good models for the industrial used tetragonal ZrO2
      supports.

PMID- 16633645
TI  - On the trapping of SOx on CaO-Al2O3-based novel high capacity sorbents.
AB  - Calcium-aluminum mixed oxide based materials doped with Na and Mn were explored
      as sulfur trapping materials. The materials showed a three times higher total
      storage capacity and a higher time on stream with complete SO2 removal compared
      to a second generation SOx trapping material which was mesoporous with calcium
      mainly present in oxidic form. Combining in situ XANES at the S K-edge and IR
      spectroscopy the key properties of the storage materials and the affiliated
      storage processes were identified. CaO-Al2O3 acts as the primary support and
      storage component, while Na+ cations adjust the base strength and enhances the
      storage capacity. Manganese cations provide the appropriate oxidation capacity in
      absence and presence of up to 10% water. The transport into the bulk phase, which
      is markedly influenced by a layer of sorbed water, is the rate-limiting step in
      presence of Mn cations. In the absence of manganese cations the oxidation step
      appears controlling the rate. The overall reaction network, identified by in situ
      IR spectroscopy and the 2D Correlation Analysis, is similar on all materials.

PMID- 16633646
TI  - Reactivity of V2O3(0001) surfaces: molecular vs dissociative adsorption of water.
AB  - The adsorption of water on V2O3(0001) surfaces has been investigated by thermal
      desorption spectroscopy, high-resolution electron energy loss spectroscopy, and X
      ray photoelectron spectroscopy with use of synchrotron radiation. The V2O3(0001)
      surfaces have been generated in epitaxial thin film form on a Rh(111) substrate
      with three different surface terminations according to the particular preparation
      conditions. The stable surface in thermodynamic equilibrium with the bulk is
      formed by a vanadyl (VO) (1x1) surface layer, but an oxygen-rich
      (radical3xradical3)R30 degrees reconstruction can be prepared under a higher
      chemical potential of oxygen (microO), whereas a V-terminated surface consisting
      of a vanadium surface layer requires a low microO, which can be achieved
      experimentally by the deposition of V atoms onto the (1x1) VO surface. The latter
      two surfaces have been used to model, in a controlled way, oxygen and vanadium
      containing defect centres on V2O3. On the (1x1) V=O and (radical3xradical3)R30
      degrees surfaces, which expose only oxygen surface sites, the experimental
      results indicate consistently that the molecular adsorption of water provides the
      predominant adsorption channel. In contrast, on the V-terminated
      (1/radical3x1/radical3)R30 degrees surface the dissociation of water and the
      formation of surface hydroxyl species at 100 K is readily observed. Besides the
      dissociative adsorption a molecular adsorption channel exists also on the V
      terminated V2O3(0001) surface, so that the water monolayer consists of both OH
      and molecular H2O species. The V surface layer on V2O3 is very reactive and is
      reoxidised by adsorbed water at 250 K, yielding surface vanadyl species. The
      results of this study indicate that V surface centres are necessary for the
      dissociation of water on V2O3 surfaces.

PMID- 16633647
TI  - Transient and steady state investigation of selective and non-selective reaction
      pathways in the oxidative dehydrogenation of propane over supported vanadia
      catalysts.
AB  - Mechanistic aspects of the formation of C3H6, CO and CO2 in the oxidative
      dehydrogenation of propane over VOx/gamma-Al2O3 materials have been investigated
      by means of steady state and transient isotopic tests. The materials possessed
      highly dispersed and polymerised VOx species as well as bulk-like V2O5. Propene
      was primarily formed via oxidative dehydrogenation of propane by lattice oxygen
      of VOx species. It was suggested that non-selective consecutive propene oxidation
      is initiated by the breaking of the C-C bond in the molecule by the lattice
      oxygen, forming formaldehyde as a side product, which is further oxidised to CO
      and CO2. The following order of initial steady state propene selectivity (at a
      zero degree of propane conversion) as a function of the nature of VOx species was
      established: a mixture of bulk-like V2O5 and polymerised VOx>polymerised
      VOx>highly dispersed VOx species. The low propene selectivity over highly
      dispersed VOx species was explained by the fact that these species do not fully
      cover the bare acidic surface of gamma-Al2O3 where propene adsorption and further
      oxidation take place. Thus, two different locations of COx formation were
      considered: (i) in the vicinity of acidic sites of the support and (ii) on VOx
      species. The propene selectivity over samples possessing polymerised VOx species
      and bulk-like V2O5 strongly decreased with an increasing degree of propane
      conversion. Contrarily, highly dispersed VOx species showed the lowest ability
      for consecutive propene oxidation.

PMID- 16633648
TI  - A unified view of the theoretical description of magnetic coupling in molecular
      chemistry and solid state physics.
AB  - The magnetic interactions in organic diradicals, dinuclear inorganic complexes
      and ionic solids are presented from a unified point of view. Effective
      Hamiltonian theory is revised to show that, for a given system, it permits the
      definition of a general, unbiased, spin model Hamiltonian. Mapping procedures are
      described which in most cases permit one to extract the relevant magnetic
      coupling constants from ab initio calculations of the energies of the pertinent
      electronic states. Density functional theory calculations within the broken
      symmetry approach are critically revised showing the contradictions of this
      procedure when applied to molecules and solids without the guidelines of the
      appropriate mapping. These concepts are illustrated by describing the application
      of state-of-the-art methods of electronic structure calculations to a series of
      representative molecular and solid state systems.

PMID- 16633649
TI  - Structure of a beta-sheet model system in the gas phase: analysis of the
      fingerprint region up to 10 microm.
AB  - In this communication we report on the conformational analysis of side-chains in
      the beta-sheet model system (Ac-Phe-OMe)(2) by applying IR/R2PI
      (infrared/resonant 2-photon ionisation) spectroscopy in the fingerprint region up
      to 10 microm, where in order to get information in this spectral region an
      extension of our new high energy and narrow band-width nanosecond IR laser system
      is presented.

PMID- 16633650
TI  - Modeling fluid diffusion using the lattice density functional theory approach:
      counterdiffusion in an external field.
AB  - The dependence of the diffusivity on temperature, pressure, and composition is
      not understood well; consequently, data is preferred significantly over
      correlations in most practical situations. Even in dilute gases, the
      contributions of attractions and repulsions to the diffusivity are difficult to
      understand on a molecular level without performing simulations. We have developed
      a Lattice Density Functional Theory (LDFT) approach for modeling diffusion to
      supplement existing methods that are very rigorous but computationally demanding.
      The LDFT approach is analogous to the van der Waals equation in how it accounts
      for molecular interactions in that it has first-order corrections to ideal
      behavior; it is an extension of the Equilibrium LDFT for adsorption and phase
      behavior. In this work, the LDFT approach is presented and demonstrated by
      modeling the problem of color counterdiffusion in an externally-applied potential
      field. This potential field, in combination with the intermolecular potential
      function, creates a diffusion regime in which repulsions cause oscillations in
      the density profile. Using the LDFT approach, the oscillations were described and
      attributed to nearest-neighbor and next nearest-neighbor interactions. The LDFT
      approach gives qualitative and quantitative agreement with dual control-volume
      Grand Canonical Molecular Dynamics simulations.

PMID- 16633651
TI  - Structure and dynamics of the [Zn(NH3)(H2O)5]2+ complex in aqueous solution
      obtained by an ab initio QM/MM molecular dynamics study.
AB  - A model complex of the hexahydrated zinc(ii) cation with one water substituted by
      ammonia in aqueous solution has been studied by hybrid ab initio quantum
      mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) at the double
      zeta Hartree-Fock (HF) quantum mechanical level. The first solvation shell,
      consisting of 5 + 1 ligand(s) at mean distances of 2.2 and 2.1 A, respectively,
      from the Zn(ii) ion, was found to remain stable with respect to exchange
      processes within the simulation time. The labile second shell consists on average
      of approximately 19 water molecules. For structural elucidation of the
      pentaaquozinc(ii) amine complex in aqueous solution several data sets such as
      radial distribution functions (RDF), coordination number distributions (CND) and
      different angular distributions (ADF, tilt and theta angle) were employed.
      Dynamics were characterised by the ligands' mean residence time (MRT), ion-ligand
      stretching frequencies and the vibrational and librational motions of water
      ligands. The labile second shell's MRT value decreases upon introduction of one
      NH(3) ligand to 7.2 ps from the 10.5 ps observed for the hexaaquozinc(ii)
      complex.

PMID- 16633652
TI  - High-resolution IR cavity ring-down spectroscopy of jet-cooled free radicals and
      other species.
AB  - Initial spectral results are reported from a newly constructed cavity ringdown
      spectrometer. The apparatus incorporates a slit-jet expansion, with or without a
      discharge, to produce cold sample molecules. High spectral resolution in both the
      near- and mid-IR is obtained by using stimulated Raman scattering of the pulsed
      amplified output of a cw Ti:Sa ring laser. Molecular spectra presented include
      the electronic near-IR transitions a (1)Delta(g)(-)<-- X (3)Sigma(g)(-) of O(2)
      and B (3)Pi(g)<-- A (3)Sigma(u)(+) of metastable N(2) and vibrational overtones
      of H(2)O (polyad 2) and the OH radical. Fundamental vibrational transitions of
      CH(3) (nu(3)) in the mid-IR are also observed. This apparatus has demonstrated
      the potential for obtaining high-resolution spectra of both reactive and non
      reactive species throughout the entire IR region.

PMID- 16633653
TI  - An experimental and theoretical study of ring closing dynamics in HN3.
AB  - We report on an H(D)-atom Rydberg tagging experiment for H(D)N(3) photolysis
      providing detailed dynamical information on the wavelength dependence of the H(D)
      + N(3) channel. We observe subtle yet striking changes in the photochemical
      dynamics as the photolysis energy passes through approximately 5.6 eV. In
      addition to producing linear azide with an average of approximately 40% of
      available energy appearing as translation, a second H(D)-atom producing channel
      grows in above this energy releasing only about 15%. An observed (inverse)
      isotope effect suggests that statistical decomposition on S(0) is unimportant.
      High level ab initio quantum chemical calculations reveal a transition state to
      cyclization of the N(3) moiety in H(D)N(3) on the first excited singlet (S(1))
      surface that is close in energy to the experimentally observed threshold energy
      for this "slow channel". Furthermore, the translational energy release of the
      "slow channel" is energetically consistent with cyclic-N(3) formation. This work
      provides the clearest presently available insights into how ring closure can
      occur in azide photochemistry.

PMID- 16633654
TI  - Deactivation of the first excited singlet state of thiophenols.
AB  - On the bases of picosecond and nanosecond laser flash photolysis with detection
      by emission and absorption spectroscopy, a quantitative description is given of
      all deactivation channels of the first excited singlet state of thiophenols
      ArSH(S(1)) such as fluorescence, intersystem crossing (ISC), chemical
      dissociation into radicals, and radiation-less internal conversion (IC). For this
      purpose, the photolysis of thiophenol and its methyl-, methoxy-, and chloro
      substituted derivatives was studied in solvents of increasing polarity: 1
      chlorobutane, ethanol, and acetonitrile. The fluorescence lifetime of the
      thiophenols was found to range from some hundreds of picoseconds up to a few
      nanoseconds, correlating with fluorescence quantum yields between 0.001-0.040, at
      room temperature. Depending on the substitution pattern of the aromatic ring, the
      quantum yield of the S-H bond dissociation was found to be between 0.3-0.5,
      irrespective of the solvent polarity. In laser photolysis, no triplet formation
      of the investigated compounds could be observed neither by the direct way nor by
      subsequent sensitization with beta-carotene. As a difference to the total, the
      radiation-less internal conversion (Phi(IC)>or= 0.5) was found to be the
      dominating process.

PMID- 16633655
TI  - Thermodynamic properties and phase transtions in the H2O/CO2/CH4 system.
AB  - The availability of free energy densities as functions of temperature, pressure
      and the composition of all components is required for the development of a three
      component phase field theory for hydrate phase transitions. We have broadened the
      extended adsorption theory due to Kvamme and Tanaka (J. Phys. Chem., 1995, 99,
      7114) through derivation of the free energy density surface in case of CO(2) and
      CH(4) hydrates. A combined free energy surface for the liquid phases has been
      obtained from a SRK equation of state and solubility measurements outside hydrate
      stability. The full thermodynamic model is shown to predict water-hydrate
      equilibrium properties in agreement with experiments. Molecular dynamics
      simulations of hydrates in contact with water at 200 bar and various temperatures
      allowed us to estimate hard-to-establish properties needed as input parameters
      for the practical applications of proposed theories. The 5-95 confidence interval
      for the interface thickness for the methane hydrate/liquid water is estimated to
      8.54 A. With the additional information on the interface free energy, the phase
      field theory will contain no adjustable parameters. We provide a demonstration of
      how this theory can be applied to model the kinetics of hydrate phase
      transitions. The growth of hydrate from aqueous solution was found to be rate
      limited by mass transport, with the concentration of solute close to the hydrate
      approaching the value characterizing the equilibrium between the hydrate and the
      aqueous solution. The depth of the interface was estimated by means of the phase
      field analysis; its value is close to the interface thickness yielded by
      molecular simulations. The variation range of the concentration field was
      estimated to approximately 1/3 of the range of the phase field.

PMID- 16633656
TI  - Tropospheric multiphase chemistry of 2,5- and 2,6-dimethylphenols: determination
      of the mass accommodation coefficients and the Henry's law constants.
AB  - The uptake of 2,5-dimethylphenol and 2,6-dimethylphenol on aqueous surfaces was
      measured between 279 and 293 K, using the wetted-wall flow tube technique coupled
      with UV absorption spectroscopic detection. For both compounds, the uptake
      coefficients gamma were found to be independent of the KOH scavenger
      concentration in the range of 0.01 to 1 M (pH > pK(a)) and of the liquid-gas
      contact times. In addition, the uptake coefficients and the derived mass
      accommodation coefficients alpha show a negative temperature dependence in the
      investigated temperature range. The mass accommodation coefficients decrease from
      1.1 x 10(-3) to 1.1 x 10(-4), and from 5.4 x 10(-4) to 6.4 x 10(-5) for 2,5
      dimethylphenol and 2,6-dimethylphenol, respectively. These results are used to
      discuss the incorporation of these species into the liquid using the nucleation
      theory. Henry's law constants (HLC) of both compounds were directly measured
      using a dynamic equilibrium system based on the water/air equilibrium at the
      interface within the length of a microporous tube. The measurements were
      conducted over the range 278-293 K in both deionized water and 35 g L(-1)
      solution of NaCl. At 293 K and in pure water, HLC were found to be equal to (in
      units of M atm(-1)): 2,5-dimethylphenol, HLC = (1270 +/- 240); 2,6
      dimethylphenol, HLC = (250 +/- 80). All of the values for HLC in 35 g L(-1) salt
      solution were 5-55% lower than the corresponding values in deionized water,
      depending on the compound and the temperature. These data (mass accommodation
      coefficients and Henry's law constants) were then used to estimate the
      partitioning of these phenolic compounds between gaseous and aqueous phases and
      the corresponding atmospheric lifetimes under clear sky (tau(gas)) and cloudy
      conditions (tau(multiphase)) have then been derived. The calculated multiphase
      lifetimes (in units of hours) are lower than those in gas phase at a cumulus
      temperature of 283 K (in parentheses): 2,5-dimethylphenol, 2.2 (3.5); 2,6
      dimethylphenol, 3.8 (4.2).

PMID- 16633657
TI  - Direct PEM fuel cell using "organic chemical hydrides" with zero-CO2 emission and
      low-crossover.
AB  - A series of "organic chemical hydrides" such as cyclohexane, methylcyclohexane,
      cyclohexene, 2-propanol, and cyclohexanol were applied to the direct PEM fuel
      cell. High performances of the PEM fuel cell were achieved by using cyclohexane
      (OCV = 920 mV, PD(max) = 15 mW cm(-2)) and 2-propanol (OCV = 790 mV, PD(max) = 78
      mW cm(-2)) as fuels without CO(2) emissions. The rates of fuel crossover for
      cyclohexane, 2-propanol, and methanol were estimated, and the rates of fuel
      permeation of cyclohexane and 2-propanol were lower than that of methanol. Water
      electrolysis and electro-reductive hydrogenation of acetone mediated by PEM were
      carried out and formation of 2-propanol in cathode side was observed. This system
      is the first example of a "rechargeable" direct fuel cell.

PMID- 16633658
TI  - Evolution of nickel speciation during preparation of Ni-SiO(2) catalysts: effect
      of the number of chelating ligands in [Ni(en)x(H2O)6-2x]2+ precursor complexes.
AB  - The evolution of nickel speciation during the successive preparation steps of Ni
      SiO(2) catalysts is studied by UV-Vis-NIR, FT-IR, DTG, TPR and TEM. The study
      focuses on the effect of the number of chelating ligands in the precursor
      complexes [Ni(en)(x)(H(2)O)((6-2x))](2+) (en = ethylenediamine, x = 1, 2, 3) on
      the adsorption on silica, and on nickel speciation after thermal treatment. When
      the en:Ni ratio in solution increases from 1 to 3, the most abundant complex is
      [Ni(en)(H(2)O)(4)](2+) (64% of all Ni complexes), [Ni(en)(2)(H(2)O)(2)](2+) (81%)
      and [Ni(en)(3)](2+) (61%), respectively. Equilibrium adsorption of
      [Ni(en)(x)(H(2)O)((6-2x))](2+) on SiO(2) results in the selective grafting of
      [Ni(en)(H(2)O)(4)](2+) and [Ni(en)(2)(H(2)O)(2)](2+), through the substitution of
      two labile H(2)O ligands by two surface SiO(-) groups. The surface
      [Ni(en)(H(2)O)(2)(SiO)(2)] complex formed by the grafting of
      [Ni(en)(H(2)O)(4)](2+) onto silica tends to transform into NiO and nickel
      phyllosilicate after calcination, which consequently leads to large and
      heterogeneously distributed metallic Ni particles upon reduction. In contrast,
      [Ni(en)(2)(SiO)(2)], resulting from the grafting of [Ni(en)(2)(H(2)O)(2)](2+)
      onto silica, no longer has aqua ligands able to react with other nickel complexes
      or silicium-containing species. Calcination transforms these complexes into
      isolated Ni(2+) ions, which are reduced into small metallic Ni particles with a
      more homogeneous size distribution, even at higher Ni loading.

PMID- 16633659
TI  - Supramolecular structures in nanocomposite multilayered films.
AB  - We investigate the multilayered structures of poly(ethylene)oxide/montmorillonite
      nanocomposite films made from solution. The shear orientation of a polymer-clay
      network in solution combined with simultaneous solvent evaporation leads to
      supramolecular multilayer formation in the film. The resulting films have highly
      ordered structures with sheet-like multilayers on the micrometer length scale.
      The polymer covered clay platelets were found to orient in interconnected blob
      like chains and layers on the nanometer length scale. Inside the blobs,
      scattering experiments indicate the polymer covered and stacked clay platelets
      oriented in the plane of the film. The polymer is found to be partially
      crystalline although this is not visible by optical microscopy. Atomic force
      microscopy suggests that the excess polymer, which is not directly adsorbed to
      the clay, is wrapped around the stacked platelets building blobs and the polymer
      also interconnects the polymer-clay layers. Overall our results suggest the re
      intercalation of clay platelets in films made from exfoliated polymer-clay
      solutions as well as the supramolecular order and hierarchical structuring on the
      nanometer, via micrometer to the centimeter length scale.

PMID- 16633660
TI  - Plasma-surface interaction in the context of ITER.
AB  - The decreasing availability of energy and concern about climate change
      necessitate the development of novel sustainable energy sources. Fusion energy is
      such a source. Although it will take several decades to develop it into routinely
      operated power sources, the ultimate potential of fusion energy is very high and
      badly needed. A major step forward in the development of fusion energy is the
      decision to construct the experimental test reactor ITER. ITER will stimulate
      research in many areas of science. This article serves as an introduction to some
      of those areas. In particular, we discuss research opportunities in the context
      of plasma-surface interactions. The fusion plasma, with a typical temperature of
      10 keV, has to be brought into contact with a physical wall in order to remove
      the helium produced and drain the excess energy in the fusion plasma. The fusion
      plasma is far too hot to be brought into direct contact with a physical wall. It
      would degrade the wall and the debris from the wall would extinguish the plasma.
      Therefore, schemes are developed to cool down the plasma locally before it
      impacts on a physical surface. The resulting plasma-surface interaction in ITER
      is facing several challenges including surface erosion, material redeposition and
      tritium retention. In this article we introduce how the plasma-surface
      interaction relevant for ITER can be studied in small scale experiments. The
      various requirements for such experiments are introduced and examples of present
      and future experiments will be given. The emphasis in this article will be on the
      experimental studies of plasma-surface interactions.

PMID- 16633661
TI  - Aromaticity rules for cycles with arbitrary numbers of half-twists.
AB  - A simple proof is given that the Huckel aromaticity rules generalise to cycles
      with an arbitrary number of half-twists, T; addition/removal of half-twists two
      at a time preserves all eigenvalues and degeneracies, so that closed-shell
      aromatic systems occur at pi-electron counts 4N+ 2, and antiaromatic at 4N for
      even T, and vice versa for odd T.

PMID- 16633662
TI  - Ab initio computation of low-temperature phase diagrams exhibiting miscibility
      gaps.
AB  - A new methodology for the computation of the low-temperature part of phase
      diagrams without recourse to any experimental information is presented. A central
      element is a procedure for deciding whether formation of crystalline solid
      solution phases can take place in the chemical system. Via global exploration of
      the enthalpy landscapes for many different compositions in the system, candidates
      for ordered stoichiometric and crystalline solid solution phases are identified.
      Next, their free enthalpies are computed at ab initio level and a low-temperature
      phase diagram is derived. As examples, the low-temperature phase diagrams for the
      ternary alkali halides NaCl/LiCl NaBr/LiBr and NaCl/KCl are presented.

PMID- 16633663
TI  - Vibrational dynamics of the hydrogen bond in H(2)S-HF: Fourier-transform-infrared
      spectra and ab initio theory.
AB  - The rotationally resolved infrared spectrum of the hydrogen bonded complex H(2)S
      HF and of its isotopomer D(2)S-DF in the HF/DF stretching range have been
      observed in a supersonic jet Fourier-transform infrared (FTIR) experiment and
      indicate a predissociation lifetime of 130 ps for H(2)S-HF. Complementary spectra
      taken at a temperature of 190 K in a cell without resolved rotational structure
      indicate the presence of strong anharmonic couplings between low frequency
      intermolecular modes and the HF donor stretch mode previously observed in other
      complexes with heavier acceptor molecules without rotational fine structure. The
      anharmonic analysis of the hot band progressions and of the rotational data
      confirm the coupling mechanism. The coupling constants and the absolute frequency
      of the hydrogen bonded stretch mode are in excellent agreement with theoretical
      predictions based on adiabatic variational calculations on potential surfaces
      computed at MP2 and CCSD(T) level. Complementary calculations with a
      perturbational approach further confirm the coupling model.

PMID- 16633664
TI  - Matrix isolation and low temperature solid state FTIR spectroscopic study of
      alpha-furil.
AB  - Alpha-furil [C(4)H(3)O-C(=O)-C(=O)-C(4)H(3)O] has been isolated in argon and
      xenon matrices and studied by FTIR spectroscopy, supported by DFT(B3LYP)/6
      311++G(d,p) calculations. The obtained spectra were fully assigned and revealed
      the presence in the matrices of three different conformers, all of them
      exhibiting skewed conformations around the intercarbonyl bond with the two
      C(4)H(3)O-C(=O) fragments nearly planar. The three conformers differ in the
      orientation of the furan rings relative to the carbonyl groups: the most stable
      conformer, I (C(2) symmetry; O=C-C=O intercarbonyl dihedral equal to 153.1
      degrees), has both furan rings orientated in such a way that one of their beta
      hydrogen atoms approaches the oxygen atom of the most distant carbonyl group,
      forming two H-C=C-C-C=O six-membered rings; the second most stable conformer, II
      (C(1) symmetry; O=C-C=O intercarbonyl dihedral equal to 126.9 degrees ), has one
      furan ring orientated as in I, while the second furan group is rotated by ca. 180
      degrees (resulting in an energetically less favourable H-C=C-C=O five-membered
      ring); in the third conformer, III (C(2) symmetry; O=C-C=O dihedral equal to
      106.2 degrees ), both furan rings assume the latter orientation relative to the
      dicarbonyl group. The theoretical calculations predicted the two higher energy
      forms being 5.85 and 6.22 kJ mol(-1) higher in energy than the most stable form,
      respectively, and energy barriers for conformational interconversion higher than
      40 kJ mol(-1). These barriers are high enough to prevent observation of
      conformational isomerization for the matrix isolated compound. The three possible
      conformers of alpha-furil were also found to be present in CCl(4) solution, as
      well as in a low temperature neat amorphous phase of the compound prepared from
      fast condensation of its vapour onto a suitable 10 K cooled substrate. On the
      other hand, in agreement with the available X-ray data [S. C. Biswas, S. Ray and
      A. Podder, Chem. Phys. Lett., 1987, 134, 541], the IR spectra obtained for the
      neat low temperature crystalline state reveals that, in this phase, alpha-furil
      exists uniquely in its most stable conformational state, I.

PMID- 16633665
TI  - F K-edge X-ray absorption near-edge structure (XANES) of AlF3 polymorphs:
      combining ab initio calculations with Walsh correlation diagrams.
AB  - The X-ray absorption near-edge structures (XANES) at the F K-edge of alpha
      AlF(3), beta-AlF(3) and a tetragonal AlF(3) phase are analysed by a combination
      of ab initio calculations with the FEFF8 code and a phenomenological discussion
      of local molecular orbital (MO) symmetries at the absorbing fluorine atoms. By
      means of a Walsh correlation diagram it is shown that the two intense absorption
      bands observed at the F K-edges of the AlF(3) polymorphs can be interpreted as
      transitions to anti-bonding MOs in [Al-F-Al]-units that have C(2v) and D(infinity
      h) point group symmetries. The energies of both anti-bonding orbitals are very
      insensitive to the angle between the Al-F bonds, which explains the close
      similarity of the XANES signatures from the three polymorphs. The FEFF8 analysis
      shows that the increased broadening of the XANES structure for beta-AlF(3) and
      the tetragonal AlF(3) phase is due to the superposition of the individual
      absorption spectra from the crystallographically distinct F species. The
      interpretation in terms of local MOs provides for the first time a "chemically
      intuitive" approach to investigations of solid fluorides by XANES spectroscopy
      and provides a simple conceptual framework for the discussion of the electronic
      structure in AlF(3) materials.

PMID- 16633666
TI  - A kinetic study of the reactions FeO+ + O, Fe+.N2 + O, Fe+.O2 + O and FeO+ + CO:
      implications for sporadic E layers in the upper atmosphere.
AB  - These gas-phase reactions were studied by pulsed laser ablation of an iron target
      to produce Fe(+) in a fast flow tube, with detection of the ions by quadrupole
      mass spectrometry. Fe(+).N(2) and Fe(+).O(2) were produced by injecting N(2) and
      O(2), respectively, into the flow tube. FeO(+) was produced from Fe(+) by
      addition of N(2)O, or by ligand-switching from Fe(+).N(2) following the addition
      of atomic O. The following rate coefficients were measured: k(FeO(+) + O -->
      Fe(+) + O(2), 186-294 K) = (3.2 +/- 1.5) x 10(-11); k(Fe(+).N(2) + O --> FeO(+)+
      N(2), 294 K) = (4.6 +/- 2.5) x 10(-10); k(Fe(+).O(2) + O --> FeO(+) + O(2), 294
      K) = (6.3 +/- 2.7) x 10(-11); and k(FeO(+) + CO --> Fe(+) + CO(2), 294 K) = (1.59
      +/- 0.34) x 10(-10) cm(3) molecule(-1) s(-1), where the quoted uncertainties are
      a combination of the 1sigma standard errors in the kinetic data and the
      systematic experimental errors. The surprisingly slow reaction between FeO(+) and
      O is examined using ab initio quantum calculations of the relevant potential
      energy surfaces. The importance of this reaction for controlling the lifetime of
      sporadic E layers is then demonstrated using a model of the upper mesosphere and
      lower thermosphere.

PMID- 16633667
TI  - UV induced local heating effects in TiO2 nanocrystals.
AB  - When isolated TiO(2) nanocrystals are subjected to UV light at 77 K and pressures
      below 10(-6) mbar, trapping of photogenerated hole centers occurs on the surface
      of the nanocrystals and can be tracked by time-resolved electron paramagnetic
      resonance spectroscopy. Irrespective of the selected UV irradiance used, the
      maximum concentration of trapped charges was found to be constant for a given
      number of nanocrystals ( approximately 10(15)) and corresponds to one electron
      hole pair per particle. On a time scale of seconds to minutes the dynamics for
      the trapping process depend on the number of photons with supra band gap energy.
      A local temperature rise of the TiO(2) nanocrystals was observed for irradiances
      above 1.55 mW cm(-2) (10(15) photons cm(-2) s(-1)). This is attributed to
      enhanced nonradiative recombination of photogenerated charge carriers via heat
      production and points to a substantial contribution of thermal chemistry in
      photocatalytic reaction cycles.

PMID- 16633669
TI  - Anomalous roughness evolution of rubrene thin films observed in real time during
      growth.
AB  - We study the growth and structure of thin films of the organic semiconductor
      rubrene during organic molecular beam deposition (OMBD) on silicon oxide in situ
      and in real time using X-ray scattering. Using in situ grazing incidence
      diffraction (GID) we find a small degree of local order but an otherwise largely
      disordered structure, consistent with out of plane scans. Monitoring the surface
      morphology in real time during growth, we find relatively smooth films (surface
      roughness sigma below approximately 15 A for thicknesses up to at least 600 A)
      and a significant delay before the onset of roughening. This anomalous roughening
      in the beginning and crossover to normal roughening later during growth may be
      related to conformational changes of rubrene in the early stages of growth.

PMID- 16633668
TI  - Chemical capacitance of nanoporous-nanocrystalline TiO2 in a room temperature
      ionic liquid.
AB  - The electrochemical behaviour of nanoporous TiO(2) in a room temperature ionic
      liquid (RTIL), 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)amide
      (EMITFSI), was investigated by cyclic voltammetry (CV) and impedance
      spectroscopy. Exponentially rising currents in voltammetry were attributed to the
      charging/discharging of electrons in the TiO(2) film and a charge transfer
      mechanism. The main features of the voltammetry and impedance followed the same
      trends in the ionic liquid as in other organic solvents and also in aqueous
      electrolytes. In the presence of lithium ions, the onset potential of the charge
      accumulation increased due to the change of the initial position of the TiO(2)
      conduction band. The results show that substitution of organic solvents contained
      in solar cells, supercapacitors or other electrochemical devices is in general
      feasible, though requires some adjustment in the electrolyte composition for
      optimal performance.

PMID- 16633670
TI  - Investigation of interparticle interactions of larger (4.63 nm) monolayer
      protected gold clusters during quantized double layer charging.
AB  - In this article, the effect of interparticle interactions of 4.63 nm sized
      monolayer protected gold clusters (Au MPCs) during quantized double layer (QDL)
      charging has been investigated using electrochemical techniques. Voltammetry and
      scanning tunneling microscopy have been used to compare their electron transfer
      behavior. Furthermore, since the QDL process is diffusion controlled, the
      diffusion coefficient values have been estimated at various charge steps using
      two independent electroanalytical techniques, viz. chronoamperometry and
      impedance. These results show that higher core charge facilitates higher
      diffusion coefficient values, and indicate that repulsive interactions dominate
      for charged MPCs compared to those of its neutral analogue, which are mainly
      attractive in nature. Additionally, the electron transfer rate constants at
      various charge steps have been estimated from the impedance results, showing
      comparatively faster electron transfer rate at higher charge states.

PMID- 16633671
TI  - A structural analysis of lead hydroxyvanadinite.
AB  - Hydroxyvanadinite, Pb(10)(VO(4))(6)(OH)(2), was prepared by the co-precipitation
      method and analyzed by X-ray absorption spectroscopy (XANES, EXAFS), infrared
      spectroscopy, Raman scattering and X-ray diffraction (XRD). The results showed
      that the structure is very similar to that of vanadinite, Pb(10)(VO(4))(6)Cl(2),
      with space group P6(3)/m (176) and cell parameters a = 10.2242(3) A and c =
      7.4537(2) A. A Rietveld refinement of the structure was performed using
      vanadinite as the starting model and fixing the geometry of the vanadate ion as a
      rigid body. First-principles Density Functional embedded cluster models are
      developed to analyze electronic structures, bonding, and densities of states.
      Interaction of Pb with the OH channel anion is examined in detail, as an
      important structural feature. A periodic band structure approach was used to
      obtain a further estimate of relaxed atomic coordinates.

PMID- 16633672
TI  - Molecular simulation of adsorption of alkanes in sodium MOR-type zeolites using a
      new force field.
AB  - The applicability of a recently proposed force field of Calero et al. (J. Am.
      Chem. Soc., 2004, 126, 11377) to Na-MOR zeolites is evaluated. The Henry law
      coefficients of ethane and C(5)-C(9) as well as the adsorption isotherms of
      ethane, propane, butane, and hexane in various Na-MOR zeolites are computed and
      compared with experimental values. These comparisons show that the new force
      field is suitable for Na-MOR zeolites. Furthermore, this force field is used to
      study the effects of sodium cations on the adsorption behavior of larger alkanes,
      such as C(4)-C(7), in MOR-type zeolites. These simulations give a better
      understanding of the underlying mechanisms of the cations' position and density
      influence on adsorption. In addition, a characteristic pressure named "reversal
      pressure" is introduced which characterizes the efficiency of the presence of
      cations in zeolites.

PMID- 16633673
TI  - Modifying the liquid/liquid interface: pores, particles and deposition.
AB  - The modification of the liquid/liquid interface with solid phases is discussed in
      this article. Modified interfaces can be formed with molecular assemblies, but
      here attention is focussed on solid materials such as mesoscopic particles, or
      microporous and mesoporous membranes. Charge transfer across the modified
      liquid/liquid interface is considered in particular. The most obvious consequence
      of the introduction of such modifying components is their effect on the transport
      to, and the transfer of material across, the liquid/liquid interface, as measured
      voltammetrically for example. One particularly interesting reaction is
      interfacial metal deposition, which can also be studied under electrochemical
      control: the initial formation of metal nuclei at the interface transforms it
      from the bare, pristine state to a modified state with very different reactivity.
      Deposition at interfaces between liquids is compared and contrasted with the
      cases of metal deposition in bulk solution and conventional heterogeneous
      deposition on conducting solid surfaces. Comparison is also made with work on the
      assembly of pre-formed micron and nanometre scale solids at the liquid/liquid
      interface.

PMID- 16633674
TI  - VUV photoelectron imaging of biological nanoparticles: ionization energy
      determination of nanophase glycine and phenylalanine-glycine-glycine.
AB  - The ionization energies of biological nanoparticles are determined using the
      velocity map photoelectron imaging technique. A beam of nanoparticles produced by
      aerosol methods is photoionized with tunable vacuum ultraviolet (VUV) synchrotron
      radiation. The resulting photoelectrons are detected and their angular and energy
      distributions are measured, yielding an angle-resolved photoelectron spectrum.
      The ionization energies of the nanoparticles are derived from plots of the
      photoelectron spectrum versus incident photon energy. The ionization energies of
      nanophase glycine and phenylalanine-glycine-glycine are 7.6 +/- 0.2 eV, and 7.5
      +/- 0.2 eV, respectively. X-Ray powder diffraction studies on the glycine
      nanoparticles indicate that they are crystalline in nature. The reduced
      ionization energy when compared to gas phase results suggests that the
      polarization energy in the solid is significant. The difference in the ionization
      energy between the nano and gas phase reflects this polarization energy and is
      derived to be 1.7 +/- 0.2 eV and 1.6 +/- 0.2 eV for glycine and phenylalanine
      glycine-glycine, respectively. Using these results the molecular polarizability
      of glycine is estimated to be 4.7 +/- 0.3 A3 (31.9 +/- 1.9 au).

PMID- 16633675
TI  - Size of neutral argon clusters from core-level photoelectron spectroscopy.
AB  - Theoretical models of lineshapes in Ar2p photoionization spectra have been
      calculated for free, neutral argon clusters of different sizes. The lineshape
      models are fitted to experimental spectra and used to estimate the mean cluster
      size realized in the experiment. The results indicate that size estimators
      working from stagnation conditions [R. Karnbach, M. Joppien, J. Stapelfeldt, J.
      Wormer and T.Moller, Rev. Sci. Instrum., 1993, 64, 2838] may underestimate the
      mean cluster size.

PMID- 16633676
TI  - The far from equilibrium structure of argon clusters doped with krypton or xenon.
AB  - Heterogeneous clusters created by doping Ar host clusters with Kr or Xe are shown
      to have radically different structures from the mixed clusters of the same type
      created by co-expansion of Ar-Kr or Ar-Xe gas mixtures. In contrast to the co
      expansion case, the doped mixed clusters can be produced with Kr or Xe on the
      surface and Ar in the bulk. With the doping technique it is thus possible to
      control the surface composition of a specific cluster. A study of the cluster
      properties as a function of the doping pressure is also reported for the case of
      Ar clusters doped with Xe. The clusters have been studied by means of synchrotron
      radiation based X-ray photoelectron spectroscopy.

PMID- 16633677
TI  - C 1s -->pi* excitation in variable size benzene clusters.
AB  - The C 1s -->pi* transition in molecular benzene and benzene clusters is
      investigated by photoion yields at high energy resolution. The vibrationally
      resolved band shows the same shape in clusters as in the bare molecule, but it is
      redshifted by 50 meV in small clusters, i.e. near the threshold of cluster
      formation. This redshift increases to 70 meV with increasing cluster size. The
      results are assigned in comparison with ab initio calculations on model
      structures of dimers, trimers, and tetramers. These indicate that different
      carbon sites in the molecular moieties give rise to distinct spectral shifts,
      where carbon sites that are pointing to the pi-system of another molecule show a
      larger redshift than the other ones. Such structural properties are found in
      solid benzene, so that the gas-to-solid shift of C 1s -->pi* excited benzene is
      derived to be a redshift which is of the order of 100-180 meV.

PMID- 16633678
TI  - Shape resonances in molecular clusters: the 2t(2g) shape resonances in S 2p
      excited sulfur hexafluoride clusters.
AB  - Sulfur hexafluoride clusters are investigated in the S 2p excitation regime. For
      the first time special emphasis is put on high-energy resolution spectroscopy of
      shape resonances in free clusters. We have investigated the 2t(2g)-shape
      resonance occurring above the S 2p threshold as one typical example to study size
      effects that are related to shape resonances. A small redshift of this resonance
      of 30 +/- 5 meV occurs in clusters relative to the free molecule and changes in
      line shape are observed. A double-barrier optical potential model is applied for
      the analysis of intra- and intermolecular effects occurring in SF6 clusters,
      which is suitable for rationalizing the experimentally observed spectral changes.
      The experimental and theoretical results are briefly discussed in comparison to
      previous work on core-excited van der Waals clusters containing diatomic
      molecules.

PMID- 16633679
TI  - Quantification of ion-induced molecular fragmentation of isolated 2-deoxy-D
      ribose molecules.
AB  - Recent experiments on low energy ion-induced damage to DNA building blocks
      indicate that ion induced DNA damage is dominated by deoxyribose disintegration
      (Phys. Rev. Lett., 2005, 95, 153201). We have studied interactions of keV H+ and
      He(q+) with isolated deoxyribose molecules by means of high resolution time-of
      flight spectrometry. Extensive statistical fragmentation of the molecules is
      observed. The fragment distribution is found to follow a power law dependence.
      The exponent can be used to characterize and quantify the molecular damage.

PMID- 16633680
TI  - Mechanism of nuclear spin initiated para-H2 to ortho-H2 conversion.
AB  - In this paper a quantitative explanation for a diamagnetic ortho/para H2
      conversion is given. The description is based on the quantum-mechanical density
      matrix formalism originally developed by Alexander and Binsch for studies of
      exchange processes in NMR spectra. Only the nuclear spin system is treated
      quantum-mechanically. Employing the model of a three spin system, the reactions
      of the hydrogen gas with the catalysts are treated as a phenomenological rate
      process, described by a rate constant. Numerical calculations reveal that for
      nearly all possible geometrical arrangements of the three spin system an
      efficient spin conversion is obtained. Only in the chemically improbable case of
      a linear group H-X-H no spin conversion is obtained. The efficiency of the spin
      conversion depends strongly on the lifetime of the H-X-H complex and on the
      presence of exchange interactions between the two hydrogens. Even moderate
      exchange couplings cause a quench of the spin conversion. Thus a sufficiently
      strong binding of the dihydrogen to the S spin is necessary to render the
      quenching by the exchange interaction ineffective.

PMID- 16633682
TI  - Matrix effects on copper(II)phthalocyanine complexes. A combined continuous wave
      and pulse EPR and DFT study.
AB  - The effect of the electron withdrawing or donating character of groups located at
      the periphery of the phthalocyanine ligand, as well as the influence of polar and
      nonpolar solvents are of importance for the redox chemistry of metal
      phthalocyanines. Continuous wave and pulse electron paramagnetic resonance and
      pulse electron nuclear double resonance spectroscopy at X- and Q-band are applied
      to investigate the electronic structure of the complexes Cu(II)phthalocyanine
      (CuPc), copper(II) 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine (CuPc(t)),
      and copper(II) 1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexadecafluoro-29H,31H
      phthalocyanine (CuPc(F)) in various matrices. Isotope substitutions are used to
      determine the g values, the copper hyperfine couplings and the hyperfine
      interactions with the 14N, 1H and 19F nuclei of the macrocycle and the
      surrounding matrix molecules. Simulations and interpretations of the spectra are
      shown and discussed, and a qualitative analysis of the data using previous
      theoretical models is given. Density functional computations facilitate the
      interpretation of the EPR parameters. The experimental g, copper and nitrogen
      hyperfine and nuclear quadrupole values are found to be sensitive to changes of
      the solvent and the structure of the macrocycle. To elucidate the electronic,
      structural and bonding properties the changes in the g principal values are
      related to data from UV/Vis spectroscopy and to density functional theory (DFT)
      computations. The analysis of the EPR data indicates that the in-plane metal
      ligand sigma bonding is more covalent for CuPc(t) in toluene than in sulfuric
      acid. Furthermore, the out-of-plane pi bonding is found to be less covalent in
      the case of a polar sulfuric acid environment than with nonpolar toluene or H2Pc
      environment, whereby the covalency of this bonding is increased upon addition of
      tert-butyl groups. No contribution from in-plane pi bonding is found.

PMID- 16633681
TI  - Efficient vibrational relaxation of O2(X 3sigma(g)-, nu = 8) by collisions with
      CF4.
AB  - A laser flash photolysis-laser-induced fluorescence (LIF) technique has been
      employed to study the relaxation kinetics of vibrationally excited O2(X 3sigma(g)
      . The time-resolved LIF excited B 3sigma(u)(-)-X 3sigma(g)- system has been
      recorded and analyzed by the integrated-profiles method. The rate coefficient for
      vibrational relaxation of O2(X 3sigma(g)-, nu = 8) by collisions with CF(4), [1.4
      +/- 0.3(2sigma)] x 10(-11) cm3 molecule(-1) s(-1), indicates that CF4 is an
      efficient relaxant of O2(X 3sigma(g)- and that the propensity rule for O2
      relaxation suggested by Mack et al. (J. A. Mack, K. Mikulecky and A. M. Wodtke,
      J. Chem. Phys., 1996, 105, 4105) has been observed experimentally.

PMID- 16633684
TI  - Reaction route control by microperoxidase-9/CTAB micelle ratios.
AB  - Microperoxidases (MP) as water-soluble models attract interest to studying the
      reaction mechanism of peroxidases because these heme peptides are able to form
      the same enzyme intermediates during the reaction with peroxides. In this work we
      have demonstrated that the association of Fe(III)MP-9 and Fe(III)MP-11 with CTAB
      micelles (MP-9/CTAB and MP11/CTAB) provides a microenvironment with an alkaline
      interface and a hydrophobic core that exhibits peroxidase behavior. This
      microenvironment shifts positively the redox potential of microperoxidases by
      approximately 100 mV. tert-Butylhydroperoxide (t-BuOOH) when added to the medium,
      converted Fe(III)MP-9/CTAB to MP-9/CTAB Compound II, a high valence oxidized
      intermediate of the heme peptide. Subsequent addition of diphenylacetaldehyde
      (DPAA) to MP-9/CTAB Compound II regenerated the native form of the enzyme,
      Fe(III)MP-9/CTAB, what characterizes the occurrence of a peroxidase cycle.
      Fe(III)MP-9/CTAB regenerated during the peroxidase cycle reacted with residual
      DPAA in the medium to form Fe(II)MP-9/CTAB, which indicates that both Fe(III)MP
      9/CTAB and its oxyferryl form can use aldehydes as reducing agents. According to
      the determined reduction potential, Fe(III)MP-9 and Fe(III)MP-9/CTAB should be
      able to oxidize DPAA (reduction potential -630 mV). The reaction of MP-9/CTAB
      with DPAA produced benzophenone as final product, detected by infrared
      spectroscopy and mass spectrometry. Interestingly, a significant difference was
      observed in the benzophenone yield according to the micelle/MP-9 molar ratio.

PMID- 16633683
TI  - REMPI-TOF studies of the translational anisotropy and the polarization of the O
      ((1)D2) photofragment angular momentum following ozone photolysis at 298 nm.
AB  - The translational anisotropy and the polarization of the electronic angular
      momentum of the O ((1)D2) fragment produced from the 298 nm photodissociation of
      ozone have been determined using resonance enhanced multiphoton ionization
      (REMPI) in conjunction with time-of-flight mass spectrometry (TOFMS). The
      translational anisotropy parameter beta, which is necessarily averaged over the
      O2 co-fragment rotational distribution, is measured to be 1.08 +/- 0.04. This is
      consistent with that expected for the (1)B2 <-- (1)A1 transition within an
      impulsive model if the tangential velocity associated with the zero point motion
      of the bend is constricted to opening the bond angle. Molecular frame
      polarization parameters of rank up to k = 4 have been extracted for the O ((1)D2)
      fragment and the calculated m(J) populations show a strong preference for the
      absolute value(m(J)) = 1 states. A small coherence term is also observed, a
      manifestation of the nuclear geometry of the dissociating molecule and the
      existence of possible non-adiabatic processes in the exit channel. The
      orientation associated with the mapping of the photon helicity onto the O ((1)D2)
      electronic angular momentum distribution was observed to have been quenched.
      However, the parameter gamma1', which describes the contribution to the
      orientation from a coherent superposition of a parallel and perpendicular
      excitation where the photofragment angular momentum lies perpendicular to both
      the recoil velocity and to the transition dipole moment, was determined to be 
      0.06.

PMID- 16633685
TI  - Benchmark database of accurate (MP2 and CCSD(T) complete basis set limit)
      interaction energies of small model complexes, DNA base pairs, and amino acid
      pairs.
AB  - MP2 and CCSD(T) complete basis set (CBS) limit interaction energies and
      geometries for more than 100 DNA base pairs, amino acid pairs and model complexes
      are for the first time presented together. Extrapolation to the CBS limit is done
      by using two-point extrapolation methods and different basis sets (aug-cc-pVDZ -
      aug-cc-pVTZ, aug-cc-pVTZ - aug-cc-pVQZ, cc-pVTZ - cc-pVQZ) are utilized. The
      CCSD(T) correction term, determined as a difference between CCSD(T) and MP2
      interaction energies, is evaluated with smaller basis sets (6-31G** and cc-pVDZ).
      Two sets of complex geometries were used, optimized or experimental ones. The
      JSCH-2005 benchmark set, which is now available to the chemical community, can be
      used for testing lower-level computational methods. For the first screening the
      smaller training set (S22) containing 22 model complexes can be recommended. In
      this case larger basis sets were used for extrapolation to the CBS limit and also
      CCSD(T) and counterpoise-corrected MP2 optimized geometries were sometimes
      adopted.

PMID- 16633686
TI  - Quadrupolar coupling selective cross-polarization in solid state NMR.
AB  - A new strategy is presented for achieving selective heteronuclear polarization
      transfers from half-integer quadrupolar spins in magic-angle spinning (MAS) NMR.
      By combining cross-polarization with a recently introduced RAPT pulse sequence
      that selectively excites the signal of a half-integer quadrupolar nucleus based
      on its quadrupolar coupling constant magnitude, we demonstrate that hetero-nuclei
      in its close proximity may be selectively excited. Selective 23Na --> 1H
      polarization transfers are demonstrated in Na2MoO4 x 2 H2O, Na2HPO4 x 2 H2O and a
      mixture of NaHCO3 and Na2HPO4 x 2 H2O.

PMID- 16633688
TI  - Restoring detailed balance in the Landau-Teller probabilities for collision
      induced vibrational transitions.
AB  - The general quasi-classical treatment for collision-induced vibrational
      transitions in diatomic molecules, under near-adiabatic conditions, is used to
      derive quantum corrections for probabilities, calculated in the external field
      approximation originally used by Landau and Teller. The quantum corrections are
      expressed through the Landau-Teller classical collision time. The first-order
      correction to the classical exponent restores detailed balance for up- and down
      transitions and does not depend on the properties of the bath except for its
      temperature. The limits of applicability of the first-order correction are
      discussed.

PMID- 16633687
TI  - Reactivity of titanium dimer and molecular nitrogen in rare gas matrices.
      Vibrational and electronic spectra and structure of Ti2N2.
AB  - The reactivity of diatomic titanium with molecular nitrogen has been investigated
      in rare gas matrices. The formation of Ti2N2 from the condensation of effusive
      beams of Ti and N2 in neon and argon matrices is observed after sample
      deposition. Our results also show that the in situ formation results from the
      spontaneous reaction at 9 K of ground state Ti2 with N2. Several low-lying
      excited states of Ti2N2 are also observed between 0.78 and 1.1 eV above the
      ground state, leading to a complex sequence of interacting vibronic transitions,
      merging into a broad continuum above 1.25 eV. Observations of Ti2(14)N2,
      Ti2(15)N2 and Ti2(14)N(15)N isotopic data enable the determination of all
      fundamental vibrations in the ground electronic state. Semi-empirical harmonic
      potential calculations lead to estimates of 3.22 N cm(-1) for the Ti-N bond force
      constant and 90 +/- 5 degrees for the bond angles. Comparisons with TiN diatomic
      data suggest a near square-planar structure with 175 +/- 3 pm TiN bond distance.
      Quantum chemical calculations at various levels indicate a 1A(g) ground state
      with a Ti-N distance close to 180 pm and 89 degrees for the NTiN bond angle, and
      give fundamental frequencies in excellent agreement with the experimentally
      observed values. Further MRCI calculations on all low-lying states enable an
      interpretation of the complex electronic spectrum in the NIR region.

PMID- 16633689
TI  - Molecular dynamics simulations of a chemical reaction; conditions for local
      equilibrium in a temperature gradient.
AB  - We have examined a simple chemical reaction in a temperature gradient; 2F <==>
      F2. A mechanical model was used, based on Stillinger and Weber's 2- and 3-body
      potentials. Equilibrium and non-equilibrium molecular dynamics simulations showed
      that the chemical reaction is in local thermodynamic as well as in local chemical
      equilibrium (delta(r)G = 0) in the supercritical fluid, for temperature gradients
      up to 10(12) K m(-1). The reaction is thus diffusion-controlled. The velocity
      distributions of both components were everywhere close to being Maxwellian. The
      peak distributions were shifted slightly up or down from the average velocity of
      all particles. The shift depended on the magnitude of the temperature gradient.
      The results support the assumption that the entropy production of the reacting
      mixture can be written as a product sum of fluxes and forces. The temperature
      gradient promotes interdiffusion of components in the stationary state, a small
      reaction rate and an accumulation of the molecule in the cold region and the atom
      in the hot region.

PMID- 16633690
TI  - The photolysis of ortho-nitrophenols: a new gas phase source of HONO.
AB  - Formation of nitrous acid (HONO) in the gas phase has been observed for the first
      time in a flow tube photoreactor upon irradiation (lambda = 300-500 nm) of 2
      nitrophenol and methyl substituted derivatives using a selective and sensitive
      instrument (LOPAP) for the detection of HONO. Formation of HONO by heterogeneous
      NO2 photochemistry has been excluded, since production of NO2 under the
      experimental conditions is negligible. Variation of the surface to volume ratio
      and the nitrophenol concentration showed that the photolysis occurred in the gas
      phase indicating that HONO formation is initiated by intramolecular hydrogen
      transfer from the phenolic OH group to the nitro group. From the measured linear
      dependence of the HONO formation rate on the reactant's concentration and
      photolysis light intensity, a non-negligible new HONO source is proposed for the
      urban atmosphere during the day. Unexpectedly high HONO mixing ratios have been
      observed recently in several field campaigns during the day. It is proposed that
      the photolysis of aromatic compounds containing the ortho-nitrophenol entity
      could help to explain, at least in part, this high contribution of HONO to the
      oxidation capacity of the urban atmosphere.

PMID- 16633691
TI  - What can a "quantum black-box" do for the inorganic thermochemist?
AB  - Enthalpies of formation of ABO3 (A = Ca, Sr, Ba; B = Ti, Zr, Hf) from the binary
      constituent oxides have been calculated by ab initio density functional theory.
      The resulting values compare well with the large number of experimental
      determinations reported in literature. The trends in the calculated enthalpies of
      formation correlate with the difference in acidity between the binary constituent
      oxides. Density functional theory is shown to be a valuable tool that should be
      used routinely in thermochemical studies of inorganic compounds.

PMID- 16633692
TI  - Toward a DFT-based molecular dynamics description of Co(II) binding in sulfur
      rich peptides.
AB  - In this paper, we investigated the reliability of a Car-Parrinello molecular
      dynamics (CPMD) approach to characterize the binding of Co(II) metal cation to
      peptide molecules containing cysteine. To this end, we compared pseudo-potentials
      and DFT plane wave expansion, which are used as key ingredients in the CPMD
      method, with standard all-electron Gaussian basis set DFT calculations. The
      simulations presented here are the first attempts to characterize interactions
      and dynamics of Co(II) metal with the building blocks of phytochelatin peptide
      molecules. Benchmark calculations are performed on [Co(Cys-H)]+ and
      [Co(Glutathione-H)]+ complexes, since they are the main fragments of the Co(II)
      Cys and Co(II)-glutathione systems found in gas phase electrospray ionisation
      mass spectrometry (ESI-MS) experiments done in our laboratory. We also present
      benchmark calculations on the [Co(H2O)6)]2+ cluster with direct comparisons to
      highly correlated ab initio calculations and experiments. In particular, we
      investigated the dissociation path of one water molecule from the first hydration
      shell of Co(II) with CPMD. Overall, our molecular dynamics simulations shed some
      light on the nature of the Co(II) interaction and reactivity in Co(II)
      phytochelatin building block systems related to the biological and environmental
      activity of the metal, either in the gas or liquid phase.

PMID- 16633693
TI  - Intramolecular energy-transfer processes in a bis(porphyrin)-ruthenium(II)
      bis(2,2':6',2''-terpyridine) molecular array.
AB  - A molecular triad has been synthesized comprising two free-base porphyrin
      terminals linked to a central ruthenium(II) bis(2,2':6',2''-terpyridine) subunit
      via meso-phenylene groups. Illumination into the ruthenium(II) complex is
      accompanied by rapid intramolecular energy transfer from the metal-to-ligand,
      charge-transfer (MLCT) triplet to the lowest-energy pi-pi* triplet state
      localized on one of the porphyrin subunits. Transfer takes place from a
      vibrationally excited level which lowers the activation energy. The electronic
      coupling matrix element for this process is 73 cm(-1). Selective illumination
      into the lowest-energy singlet excited state (S1) localized on the porphyrin
      leads to fast singlet-triplet energy transfer that populates the MLCT triplet
      state with high efficiency. This latter process occurs via Dexter-type electron
      exchange at room temperature, but the activation energy is high and the reaction
      is prohibited at low temperature. For this latter process, the electronic
      coupling matrix element is only 8 cm(-1).

PMID- 16633694
TI  - Electrochemical studies of porphyrin-appended dendrimers.
AB  - The electrochemical properties of porphyrin-appended dendrimers containing 2-, 4
      , 8-, 16-, 32- and 64-porphyrin macrocycles in their free-base and zinc(II) forms
      have been investigated. Both series gave diffusional based voltammetric responses
      in dichloromethane. There was minimal effect of dendrimer generation on the redox
      potentials. Multiple pi-cation and anion radicals as well as dications and
      dianions were formed on the surface of the dendrimers on oxidation or reduction
      as appropriate, with each cyclic voltammetric wave representing electron transfer
      to or from multiple non-interacting porphyrin sites. Electrostatic interactions
      in the higher generation dendrimers result in kinetic effects being observed for
      the highly charged species generated when each porphyrin unit is doubly or triply
      oxidised. The number of electrons transferred on reduction or oxidation of the
      dendrimers was evaluated using steady-state microelectrode voltammetry. For the
      lower generations of species a good correlation was observed between numbers of
      electrons transferred and number of porphyrin entities per molecule; for the
      dendrimers containing 32 and 64 units, however, slight negative deviations were
      observed, possibly due to electrostatic interactions as the porphyrins become
      closer packed.

PMID- 16633695
TI  - Influence of internal energy and impact angle on the sticking behaviour of
      reactive radicals in thin a-C:H film growth: a molecular dynamics study.
AB  - In this molecular dynamics study, we investigate the influence of the internal
      energy and the impact angle on the sticking coefficients of several hydrocarbon
      radicals on a hydrogenated amorphous carbon surface. The selected radical species
      and their kinetic energy were determined experimentally. However, no information
      is available regarding their internal energy, nor on their impact angles. It is
      shown that the internal energy has a considerable influence on the sticking
      coefficient, which is dependent on the kind of species. The impact angle,
      however, is shown to be of minor importance.

PMID- 16633696
TI  - Influence of diffusion on pore size distributions determined by xenon porometry.
AB  - Xenon porometry is a new method for characterization of porous materials. In this
      method, the material is immersed in a medium, and its properties are studied by
      means of 129Xe NMR spectra of xenon dissolved in the sample. The method is
      particularly suitable for the determination of pore size distribution of the
      material, since the spectra display two signals whose chemical shift is dependent
      on the pore size. A prerequisite for an accurate determination is the fact that
      the diffusion of xenon between different pores is slow enough. The diffusion is
      studied in this work using two-dimensional exchange spectroscopy (2-D EXSY). The
      spectra measured as a function of the mixing time imply that the exchange is
      really slow as compared with the NMR time scale, and therefore the distribution
      of the resonance frequencies indeed represents the pore size distribution.

PMID- 16633697
TI  - Controlled bimolecular collisions allow sub-diffraction limited microscopy of
      lipid vesicles.
AB  - The concentration and vesicle size-controlled collisions of single molecules with
      target biological assemblies allow sub-diffraction limited optical images to be
      obtained that are not subject to the usual photobleaching problems with single
      molecule experiments. For example, single molecules of the probe Nile Red in
      aqueous solution emit a burst of fluorescence when they collide with a 50 nm
      hydrophobic vesicle situated on the surface in the laser focus. The bimolecular
      kinetics of the bursts is defined by their on- and off-time distribution
      functions which depend on the concentration and diffusion of the probe and the
      vesicle size. The mean burst frequency changes much more sharply than does the
      fluorescence intensity when a vesicle is raster scanned through the laser focus.
      This sharpness allows the spatial resolution of two objects to be improved and
      separations less than the diffraction limited resolution of the conventional
      optical microscope to be measured. The principle of this method of trajectory
      time distribution optical microscopy (TTDOM) could be used in a far field optical
      microscopic system with a resolution of several nanometers.

PMID- 16633698
TI  - Synthesis and reactivity of N@C60O.
AB  - The endohedral fullerene epoxide N@C60O was synthesised, isolated by High
      Performance Liquid Chromatography (HPLC), and characterised by Electron Spin
      Resonance (ESR). This nitrogen radical displays predominantly axial symmetry
      characteristics as expected for a monoadduct, evidenced by a zero-field splitting
      D parameter of 6.6 MHz and an E parameter of 0.5 MHz in powder at 77 K. Photo-
      and thermally-activated silencing of the nitrogen radical were observed, the
      latter showing the evolution of a new spin signal during heating at 100 degrees
      C. We suggest that loss of nitrogen spin is due to coupling with a radical formed
      by opening of the epoxide ring. This implies that the reaction of C60O with C60
      in the solid state proceeds via a radical, rather than ionic, intermediate.

PMID- 16633699
TI  - White matter lesions and cognitive impairment as silent cerebral disease in
      hypertension.
AB  - Although the pathogenesis and clinical significance of cerebral white matter
      lesions remain controversial, it is well established that age and hypertension
      are the most important factors related to the presence of these lesions.
      Hypertension is known to be the most important factor for developing stroke and
      vascular dementia. In addition, the presence of cerebral white matter lesions is
      an important prognostic factor for the development of stroke, and also for
      cognitive impairment and dementia. The mechanisms underlying hypertension-related
      cognitive changes are complex and are not yet fully understood. Correlations
      between cerebral white matter lesions and elevated blood pressure provide
      indirect evidence that structural and functional changes in the brain over time
      may lead to lowered cognitive functioning when blood pressure control is poor or
      lacking. Some authors have suggested that the presence of white matter lesions in
      hypertensive patients could be considered an early marker of brain damage.

PMID- 16633700
TI  - Novel therapeutic approaches to the treatment of chronic abdominal visceral pain.
AB  - Chronic abdominal visceral pain (CAVP) has a significant clinical impact and
      represents one of the most frequent and debilitating disorders in the general
      population. It also leads to a significant economic burden due to workdays lost,
      reduced productivity, and long-term use of medications with their associated side
      effects. Despite the availability of several therapeutic options, the management
      of patients with CAVP is often inadequate, resulting in frustration for both
      patients and physicians. This may in part be explained by the lack of
      understanding of the mechanisms underlying chronic pain; in contrast with acute
      pain in which the pathophysiology is relatively well known and has several
      satisfactory therapeutic options. Recently, the development of tools for brain
      investigation, such as functional magnetic resonance imaging, has provided new
      insights on the pathophysiology of chronic pain. These new data have shown that
      plastic changes in the central and peripheral nervous system might play an
      important role in the maintenance of chronic pain. Therefore, approaches aimed at
      the modulation of the nervous system, rather than the ones interfering with the
      inflammatory pathways, may be more effective for chronic pain treatment. We
      propose that noninvasive central nervous system stimulation, with transcranial
      magnetic stimulation (TMS), might be a novel therapeutic option for CAVP. This
      paper will present an overview of the pathophysiology and the available therapies
      for CAVP, focusing on the recent advances in the treatment of this pathology.

PMID- 16633701
TI  - The role of glycosylation in the secretion of proteoglycans.

PMID- 16633704
TI  - Transabdominal gastro-esophageal devascularization and esophageal transection for
      bleeding esophageal varices after failed injection sclerotherapy: long-term
      follow-up report.
AB  - BACKGROUND: Management of continued bleeding from esophageal varices despite
      adequate injection sclerotherapy remains one of the medical and surgical
      dilemmas. Transabdominal gastroesophageal devascularization and esophageal
      transection (TGDET) is considered an effective and safe procedure for such
      patients. AIM: This study aimed at presenting continued evaluation of TGDET.
      Various problems influencing the early outcome are discussed, and long-term
      outcome is analyzed. DESIGN: This was a prospective clinical descriptive study.
      METHODS: Prospective data was collected on 142 consecutive patients managed by
      one group of surgeons over a 5 year-period and 15 years follow-up after failed
      injection sclerotherapy for variceal bleeding. Evaluation was made in terms of
      effectiveness in controlling the acute bleeding, postoperative morbidity and
      mortality, recurrent bleeding, encephalopathy, and long-term survival. RESULTS:
      There were 133 men and 9 women. Mean age was 41.8 years. Etiology of portal
      hypertension was bilharziasis in 54.9% and posthepatitic in 14.8%. Child-Pugh
      grading on admission was A: 47.2%, B: 28.8%, and C: 14%. Hemorrhage was
      controlled in all cases. Clinical leak was observed in 5.6%, portal vein
      thrombosis in 6.3%, and staple line erosion in 2.1% of cases. No patient
      developed encephalopathy. In-hospital mortality was 12.7%. Complete eradication
      of varices was observed in 70.6% patients. Recurrent variceal bleeding was
      noticed in 6.9% of cases. Actuarial 15-year survival for Child-Pugh A patients
      was 44%, B was 22.5%, and none for C. CONCLUSION: TGDET remains a safe and
      effective procedure after failure of sclerotherapy when other alternatives are
      either not indicated or not available.

PMID- 16633706
TI  - Lupus and leg ulcers--a diagnostic quandary.
AB  - Leg ulcerations can occur in systemic lupus erythematosus (SLE) patients with
      antiphospholipid (aPL) antibodies and/or vasculitis, and it has been suggested
      that aPL antibodies may play a pathogenetic role in skin manifestations of SLE.
      To our knowledge, there is only one report of an aPL antibody-negative patient
      who developed pyoderma gangrenosum (PG) several years before the diagnosis of
      SLE. We describe a case of a young male affected by SLE who developed leg ulcers
      diagnosed as PG in the absence of aPL antibodies, where the onset of PG was
      associated with reactivation of SLE. Effective treatment led to significant
      improvement in skin lesions and SLE activity.

PMID- 16633707
TI  - Articular damage in late rheumatoid arthritis.
AB  - This study aims to examine the long-term articular damage in rheumatoid arthritis
      (RA) patients according to rheumatoid arthritis articular damage (RAAD) score and
      to evaluate the parameters correlated with this score. The RAAD score was
      assessed in 85 RA patients who had the disease for more than 10 years. Patients
      were divided into three groups according to duration of the disease: group 1, 10
      14 years; group 2, 15-19 years; and group 3, more than 20 years. Patients were
      also divided into three groups according to the time of initiation of treatment
      with disease-modifying antirheumatic drugs: group A, within the first 2 years,
      group B, between 2 and 5 years; and group C, after 5 years. We investigated the
      RAAD score relationship between groups 1, 2, 3; groups A, B, C; sex; drug
      compliance; age of onset of the disease; and Health Assessment Questionnaire
      (HAQ). We observed significant differences in RAAD scores according to groups 1,
      2, 3 (p<0.01), but not to groups A, B, C; sex; or drug compliance (p>0.05). While
      the RAAD score correlated well with the HAQ (r=0.560, p<0.001), it did not
      correlate with the age at onset of the disease (p>0.05). As RA is not a benign
      disease and articular damage progresses over time, the goal of RA therapy must be
      to maintain a response before the onset of irreversible damage and loss of
      function.

PMID- 16633708
TI  - Bilateral ankle edema with bilateral iritis.
AB  - I report two patient presented to me with bilateral symmetrical ankle edema and
      bilateral acute iritis. A 42-year-old female of Indian origin and 30-year-old
      female from Somalia both presented with bilateral acute iritis. In the first
      patient, bilateral ankle edema preceded the onset of bilateral acute iritis.
      Bilateral ankle edema developed during the course of disease after onset of
      ocular symptoms in the second patient. Both patients did not suffer any
      significant ocular problem in the past, and on systemic examination, all clinical
      parameters were within normal limit. Lacrimal gland and conjunctival nodule
      biopsy established the final diagnosis of sarcoidosis in both cases, although the
      chest x-rays were normal.

PMID- 16633709
TI  - Effectiveness of pulsed electromagnetic field therapy in lateral epicondylitis.
AB  - We aimed to investigate the efficacy of pulsed electromagnetic field (PEMF) in
      lateral epicondylitis comparing the modality with sham PEMF and local steroid
      injection. Sixty patients with lateral epicondylitis were randomly and equally
      distributed into three groups as follows: Group I received PEMF, Group II sham
      PEMF, and Group III a corticosteroid + anesthetic agent injection. Pain levels
      during rest, activity, nighttime, resisted wrist dorsiflexion, and forearm
      supination were investigated with visual analog scale (VAS). Pain threshold on
      elbow was determined with algometer. All patients were evaluated before treatment
      at the third week and the third month. VAS values during activity and pain levels
      during resisted wrist dorsiflexion were significantly lower in Group III than
      Group I at the third week. Group I patients had lower pain during rest, activity
      and nighttime than Group III at third month. PEMF seems to reduce lateral
      epicondylitis pain better than sham PEMF. Corticosteroid and anesthetic agent
      injections can be used in patients for rapid return to activities.

PMID- 16633710
TI  - Infliximab in Takayasu arteritis: a safe alternative?
AB  - OBJECTIVE: To test the efficacy of Infliximab, a chimeric monoclonal antibody
      against TNF-alpha, in the treatment of Takayasu arteritis. MATERIALS AND METHODS:
      We used infliximab at an initial dose of 3 mg/kg i.v. at weeks 0, 2, 6, and 8
      thereafter in combination with methotrexate or azathioprine, to treat four
      patients with Takayasu arteritis. RESULTS: Three out of four patients responded
      to infliximab treatment, while two of them retained the response during a two
      year follow up. A higher dose regimen (5 mg/kg), however, was eventually
      warranted for two of the responders. No major side effects were noted.
      CONCLUSIONS: Infliximab might be an effective and safe alternative for patients
      with Takayasu arteritis.

PMID- 16633711
TI  - Systematic review of measures and their concepts used in published studies
      focusing on the treatment of acute inflammatory arthritis.
AB  - To identify outcome measures and concepts cited in published studies focusing on
      the treatment of acute inflammatory arthritis, and to identify and quantify the
      concepts contained in these measures using the International Classification of
      Functioning, Disability and Health (ICF) as a reference. This 'research
      perspective' is part of the development process for an ICF core set in acute
      arthritis. Electronic searches of Medline, Embase, Cumulative Index to Nursing
      and Allied Health Literature, Pedro and the Cochrane Library from January 2000 to
      July 2004 were carried out. Data on the outcome measures and patient
      characteristics for the included studies were extracted. The items of the
      identified questionnaires and their underlying concepts were specified and then
      linked to ICF categories using standardized linkage rules. From the 401 abstracts
      retrieved, 104 studies met the inclusion criteria. From these studies, 38 formal
      assessment instruments, 62 single clinical measures, 66 technical measures and 14
      clinical criteria were identified. A total of 966 concepts were extracted, and
      84.7% of these concepts could be linked to ICF categories. The concepts contained
      in measures named in more than 5% of the studies were represented by 34 second
      level ICF categories. Ten (30%) of the 34 categories belong to the component
      "Body Functions", 3 (9%) to the component "Body Structures" and 21 (61%) to the
      component "Activities and Participation". The ICF provides a valuable reference
      to identify and quantify the concepts of outcome measures focusing on the
      management of patients with acute inflammatory arthritis. Our findings indicate
      there is good agreement on 'what should be measured' in acute inflammatory
      arthritis to allow for a comparison of patient populations.

PMID- 16633712
TI  - Infection and work stress are potential triggers of ankylosing spondylitis.
AB  - The objective of the study was to investigate potential triggering events for the
      onset of ankylosing spondylitis (AS). A large retrospective population survey of
      1,080 AS patients was carried out by multi-faceted questionnaire. A nested case
      control study compared the cohort to 102 patients with lumbar disc prolapse.
      Participants with AS had a mean age of 49.8 years, mean age of disease onset was
      25.2 years and 63% of the cohort were male. Seventy-nine per cent knew they were
      human leucocyte antigen (HLA)-B27-positive, and a further 12.5% were unaware of
      their HLA-B27 status. Infections were relatively common in the 3 months leading
      to the first symptoms, 4.6% reporting gastrointestinal infection, 2.5% reporting
      urinary tract infection and 2.6% respiratory infection. Five per cent reported
      heavy physical activity in the 3 months prior to the onset of symptoms, 4.2%
      emotional stressors and 3.1% work stressors. Injury and surgery were less
      commonly reported (1.7 and 0.7%, respectively). Pregnancy was reported by 7.4% of
      the female participants. When the 12 months leading up to the first symptoms was
      compared to the 12 months previous to that, work stressors (OR 1.5), and
      pregnancy (OR 2.5) infection (OR 1.5 to 1.8) were significantly more common
      closer to disease onset. Infection and work stressors are potential triggers for
      the onset of AS; however, low rates suggest they are only a small part of the
      environmental milieu that combines with a genetic predisposition to cause the
      development of this chronic inflammatory disease.

PMID- 16633713
TI  - Proteomic analysis of prodigiosin-induced apoptosis in a breast cancer
      mitoxantrone-resistant (MCF-7 MR) cell line.
AB  - Prodigiosin (PG) is a bacterial, red-pigmented antibiotic with immunosuppressive
      and apoptotic activities. To better understand its mechanisms of action, we tried
      to identify proteins associated with apoptosis induced by PG. For this purpose,
      the variation of protein expression on exposure to apoptotic concentrations of PG
      was examined, by high-resolution two-dimensional gel electrophoresis (2D-E), in
      the MCF-7 cancer cell line resistant to mitoxantrone (MCF-7-MR). Six PG apoptosis
      associated protein spots were further characterized by complementary peptide mass
      fingerprinting and tandem mass spectrometry data obtained on a matrix-assisted
      laser desorption ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) mass
      spectrometer. The proteins identified were involved in various cellular
      functions, including cell defence, DNA repair and cellular organization. Our data
      provide novel information on cell response to PG, a new apoptotic drug with
      interesting anticancer activity.

PMID- 16633714
TI  - Trabectedin (ET-743, Yondelis) is a substrate for P-glycoprotein, but only high
      expression of P-glycoprotein confers the multidrug resistance phenotype.
AB  - Trabectedin (ET-743, Yondelis) is a novel anticancer drug currently undergoing
      phase II and III investigations. There are various and conflicting reports
      whether trabectedin is a substrate for P-glycoprotein (P-gp), an important factor
      in drug disposition and multi-drug resistance (MDR). We have now unambiguously
      shown that trabectedin is a P-gp substrate by investigating vectorial transport
      over monolayers of LLC-PK1 pig kidney and Madine-Darby Canine kidney (MDCK) cells
      and the mdr1a and/or MDR1 transfected subclones. We further characterized the
      cytotoxic effects and cellular accumulation of trabectedin in these cell lines as
      well as in a panel of other cell lines with high or moderate expression levels of
      P-gp. Trabectedin displayed the typical MDR phenotype only in highly P-gp
      expressing cell lines, but not in cell lines with expression levels more closely
      conforming to clinical samples, suggesting that P-gp will not confer resistance
      to trabectedin in cancer patients.

PMID- 16633716
TI  - MDDD, a 4,9-diazapyrenium derivative, is selectively toxic to glioma cells by
      inducing growth arrest at G0/G1 independently of p53.
AB  - 4-Methyl-2,7-diamino-5,10-diphenyl-4,9-diaz-apyrenium chloride (MDDD), a stable
      and water soluble nucleic acid-intercalating agent, was shown to be toxic to
      cancer cells with IC50 around 10 microM. IC(50) We tested MDDD for its potential
      antitumor activities and found it inhibited cancer cell growth with IC(50) in the
      micromolar range for the majority of cancer cells tested, with the exception of
      glioma cells, for which the IC(50) is in the submicromolar range. This unique
      selectivity of MDDD to glioma cells can potentially be exploited for anti-glioma
      therapeutics. Although the underlying mechanisms for the apparent glioma
      specificity remain to be elucidated, our analysis indicates that MDDD
      significantly reduces cell clonogenicity and blockes cell proliferation at the G1
      phase. MDDD treatment also triggers induction of p53 and p21 at the protein
      levels, suggesting the activation of DNA damage response. However, MDDD mediated
      growth inhibition does not require the p53 pathway since p53+/- isogenic cell
      pairs display the same sensitivity. These properties of MDDD favor its candidacy
      for evaluation as a new anti-tumor agent, particularly for glioma.

PMID- 16633717
TI  - In vitro characterization of the human biotransformation pathways of aplidine, a
      novel marine anti-cancer drug.
AB  - Aplidine is a potent marine anti-cancer drug and is currently being investigated
      in phase II clinical trials. However, the enzymes involved in the
      biotransformation of aplidine and thus its pharmacokinetics are not known yet. To
      assess the biotransformation pathways of aplidine and their potential
      implications for human pharmacology and toxicology, the in vitro metabolism of
      aplidine was characterized using incubations with human plasma, liver
      preparations, cytochrome P450 (CYP) and uridine diphosphoglucuronosyl transferase
      (UGT) supersomes in combination with HPLC analysis and cytotoxicity assays with
      cell lines. Aplidine was metabolised by carboxyl esterases in human plasma. Using
      CYP supersomes and liver microsomes, it was shown that aplidine was metabolised
      mainly by CYP3A4 and also by CYP2A6, 2E1 and 4A11. Four metabolites were observed
      after incubation with human liver microsomes, one formed by CYP2A6 (C
      demethylation) and three by CYP3A4 (hydroxylation and/or C-dealkylation). No
      conjugation was observed in human liver S9 fraction. However, the aplidine
      metabolites formed by CYP were further conjugated by the phase II enzymes UGT,
      GST and SULT. In accordance with the findings in microsomes and CYP supersomes, a
      significant effect of specific CYP2A6, 2E1, 3A4 and 4A11 inhibitors on the
      cytotoxicity of aplidine in Hep G2 and IGROV-1 cells could be observed. These
      results provide evidence that CYP3A4 has a major role in metabolising aplidine in
      vitro with additional involvement of CYP2A6, 2E1, and 4A11. Further, the
      metabolites formed by CYPs can be conjugated by UGT, SULT and GST. These findings
      could help interpret the in vivo pharmacokinetics of aplidine.

PMID- 16633720
TI  - Pattern reversal ERG and VEP--comparison of stimulation by LED, monitor and a
      Maxwellian-view system.
AB  - PURPOSE: Pattern stimulation is widely used to detect inner retinal dysfunction.
      In this work we describe a pattern stimulation technique with LEDs and compare
      the results with conventional methods. METHODS: PERG and VEP were derived from
      three normal subjects. Three different techniques were used to generate a
      checkerboard pattern reversal stimulus: a 70 Hz monitor, a Maxwellian-view system
      equipped with a Xenon-arc lamp and a mechanical mirror system, and a LED array
      (Roland Consult) consisting of 100 white LEDs. Two kinds of luminance (125 and
      340 cd/m2) and four temporal frequencies (4, 8, 12 and 24 reversals per second)
      were studied on three healthy subjects. Additionally, a luminance tuning
      experiment (30, 60, 90, 125 and 340 cd/m2) was performed on one subject. RESULTS:
      Comparison of different stimulation techniques shows reproducible responses of
      PERG and VEP with all three methods. The LED array leads to slightly smaller
      amplitudes than both other techniques, which we ascribe to the design of the LED
      field. No difference of peak times or phases was noticed between different
      stimulation techniques. A luminance dependency of PERG and VEP is noticeable
      using stimulation with LED: with decreasing luminance we measured increasing peak
      times of PERG and VEP and decreasing amplitude of PERG. CONCLUSION: We conclude
      that central retinal stimulation with checkerboard pattern reversal is possible
      with LED. It gives comparable results to monitor and Maxwellian-view system.

PMID- 16633721
TI  - Fourier-analysed steady-state VEPs in pre-school children with and without normal
      binocularity.
AB  - Pre-school children aged 4-5 were examined with steady-state VEP in response to a
      sinusoidal grating pattern with a spatial frequency of 4 c/deg, reversing at
      rates 5, 10, and 15 Hz. Normal children (n = 10) were compared with subjects
      lacking stereo perception (n = 6) and with subjects showing significant
      unilateral amblyopia with visual acuity in the worse eye <0.5 (n = 7). Fast
      Fourier Transform was used for analysis of the crude steady-state VEP responses.
      Compared to normals, the subjects lacking stereo perception showed a
      significantly lower power of the second harmonic in the response evoked by
      binocular stimulation with gratings reversed at 15 Hz. The amblyopic group showed
      a significant difference between the dominant and the non-dominant eye regarding
      the first harmonic power in the responses evoked by gratings reversed at 5 and 10
      Hz. These findings are discussed in relation to the magnocellular and
      parvocellular visual pathways and suggested models for linear and non-linear
      processing of visual signals.

PMID- 16633722
TI  - The acute effect of cigarette smoking on pattern visual evoked potentials.
AB  - Reports of tobacco-induced electrocortical activation and decrements in ocular
      blood flow in the acute phase indicated that this effect is mediated via
      nicotine's action or neuronal systems. In this study, pattern visual evoked
      potentials were investigated in a group of male smokers (22 right eyes of 22
      subjects) in separate real smoking and sham smoking sessions. On each session,
      pattern visual evoked potentials were recorded before smoking, immediately after
      smoking, and five minutes after smoking. Latency and amplitude values for P100
      peaks were assessed and analyzed in each smoking condition for both real smoking
      and sham smoking sessions. Real smoking significantly decreased P100 latency
      values (p value related to difference between pre-smoking and immediately after
      smoking conditions is 0.009) and increased P100 amplitude values (p value related
      to difference between pre-smoking and fifth minute after smoking is 0.039).
      Statistically no significant difference was observed in sham smoking sessions.
      Our results are consistent with smoking-induced stimulant effects on pattern
      visual evoked potentials.

PMID- 16633723
TI  - Vitamin A deficiency modifies the mfERG: a case study of rod influence on the
      mfERG.
AB  - We report an observational case study which showed that the rod pathway may have
      a significant effect on the multifocal electroretinogram (mfERG). A 68-year-old
      lady diagnosed with Vitamin A deficiency underwent standard ERG and mfERG. ERG
      rod and cone function were analysed and the first order mfERG responses were
      determined. At presentation, there was no demonstrable rod function on ERG
      testing and normal cone function. mfERG P1 amplitude responses were normal but
      mfERG P1 latency responses were significantly delayed. Four weeks after
      initiating treatment with intramuscular Vitamin A, ERG rod function significantly
      improved. However, cone amplitude was reduced and the 30 Hz flicker latencies
      decreased. Furthermore, mfERG P1 latency returned to normal and interestingly
      mfERG P1 amplitude responses showed a significant reduction. These results alter
      our understanding of the mfERG response by indicating that there is a possible
      inhibitory influence on mfERG responses from rod pathway systems.

PMID- 16633724
TI  - Retinal function in rabbits does not improve 4-5 months after terminating
      treatment with vigabatrin.
AB  - PURPOSE: We have previously reported changes in retinal function and
      histopathology in rabbits treated with vigabatrin. The purpose of the present
      study was to evaluate retinal function and histopathology of retina in rabbits 4
      5 months after terminating vigabatrin medication. METHODS: Five rabbits were
      treated with a daily per oral dose of vigabatrin during 12-13 months. After
      terminating treatment an observation period of 4-5 months followed. Six rabbits
      receiving water served as controls. Standardized full-field electroretinograms
      were performed every 6-8 weeks, using a Burian-Allen bipolar contact lens. After
      18 months the rabbits were sacrificed and the morphology of the sectioned retina
      was studied. The antibodies used for staining were GABA, GFAP, GAD, and vimentin.
      RESULTS: After 12-13 months of treatment the full-field ERG was reduced in all
      rabbits treated with vigabatrin. There was a statistically significant difference
      in the dark adapted cone b-wave amplitude between treated animals and controls
      (Wilcoxon signed-rank test, p = 0.043). This difference was consistent also 4-5
      months after terminating treatment. Immunohistology of the sectioned retina
      demonstrated no significant difference in immunoreactivity between treated
      animals and controls. All treated rabbits demonstrated elevated serum
      concentration of the drug during medication. CONCLUSION: Four to five months
      after terminating treatment with vigabatrin the rabbit full-field ERG remains
      reduced in isolated cone b-wave amplitude indicating that vigabatrin induced
      retinal dysfunction may be irreversible. However, immunohistology is normal after
      a period without treatment, implying that the previously described changes in
      retinal morphology and glial cell activity are reversible, and probably exist
      only during treatment.

PMID- 16633725
TI  - Wide field multifocal and standard full field electroretinographic features of
      hemi retinal vein occlusion.
AB  - The purpose of this study was to document the standard full field
      electroretinographic (ERG) and wide field multifocal electroretinographic (WF
      mfERG) findings in eyes with recent onset hemi-retinal vein occlusion (HRVO) and
      to compare the electro-diagnostic findings in the affected and fellow eyes with
      reference to normative data. Eight patients with HRVO were assessed using ERG and
      WF-mfERG. WF-mfERG first order responses from the affected hemi-retinae and the
      unaffected hemi-retinae in each affected eye were compared. WF-mfERG responses
      from each affected hemi-retina and from the symmetrical hemi-retina of each
      fellow eye were compared. ERG responses between affected and unaffected eyes were
      also compared. All electrodiagnostic tests were compared to normative data (5-95%
      confidence limits derived from age-related controls). WF-mfERG P1 and N1 implicit
      times were greater for the affected hemi-retinae than for the unaffected hemi
      retinae (p <0.05). WF-mfERG N1 and P1 implicit times were prolonged (p < 0.05)
      and WF-mfERG P1/N1 amplitude ratios were significantly reduced (p < 0.05) for the
      affected eyes when compared with the fellow eyes. Maximal b-wave, cone b-wave and
      flicker implicit times were prolonged (p < 0.05) when comparing affected and
      fellow eyes. These results indicate that retinal injury due to HRVO culminates in
      significant delay of both ERG and WF-mfERG implicit times. These results suggest
      that WF-mfERG in combination with ERG may have a role in the management of HRVO.

PMID- 16633726
TI  - Pattern reversal ERG with LED-stimulation using cyclic summation technique.
AB  - PURPOSE: Multifocal pattern reversal stimulation can be used to detect inner
      retinal dysfunction. Commonly, the stimulus is generated on a monitor using m
      sequence technique. We describe a pattern reversal ERG evoked by LED arrays using
      cyclic summation (CS). METHODS: One eye of eight healthy subjects was examined
      with an arrangement of 13 LED arrays. Each array consisted of 100 LEDs separated
      by thin walls. One of the fields was placed centrally, three fields each were
      placed above, below, left and right of the central field. CS technique at a
      temporal frequency of 16 reversals per second (RPS) was used for stimulation.
      Viewing distance was 30 cm, check size was 0.58 cyc/deg. Luminance of the bright
      fields was 340 cd/m2. RESULTS: Fourier analysis was performed. Centrally, the
      amplitude of the 2nd harmonic wave was highest (0.87 microV). In the first
      paracentral fields, amplitudes were 0.28 microV (nasally), 0.21 microV (superior,
      inferior and temporally). In the second paracentral fields, amplitudes were 0.11
      microV (nasally), 0.09 microV (superior), 0.13 microV (inferior) and 0.15 microV
      (temporally). With exception of the temporal field (0.1 microV), in the outermost
      fields no reproducible ERG response could be recorded. CONCLUSION: Peripheral ERG
      responses to a pattern reversal stimulus can be recorded with LED stimulation
      using CS technique up to an eccentricity of 30 degrees. Responses are highest
      centrally and decrease with increasing distance to the centre.

PMID- 16633731
TI  - Hydrogen peroxide activates activator protein-1 and mitogen-activated protein
      kinases in pancreatic stellate cells.
AB  - Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of
      pancreatic inflammation and fibrosis, where oxidative stress is thought to play a
      key role. Reactive oxygen species such as hydrogen peroxide (H(2)O(2)) may act as
      a second messenger to mediate the actions of growth factors and cytokines. But
      the role of reactive oxygen species in the activation and regulation of cell
      functions in PSCs remains largely unknown. We here examined the effects of
      H(2)O(2) on the activation of signal transduction pathways and cell functions in
      PSCs. PSCs were isolated from the pancreas of male Wistar rats, and used in their
      culture-activated, myofibroblast-like phenotype unless otherwise stated.
      Activation of transcription factors was examined by electrophoretic mobility
      shift assay and luciferase assay. Activation of mitogen-activated protein (MAP)
      kinases was assessed by Western blotting using anti-phosphospecific antibodies.
      The effects of H(2)O(2) on proliferation, alpha(1)(I)procollagen gene expression,
      and monocyte chemoattractant protein-1 production were evaluated. The effect of
      H(2)O(2) on the transformation of freshly isolated PSCs in culture was also
      assessed. H(2)O(2) at non-cytotoxic concentrations (up to 100 microM) induced
      oxidative stress in PSCs. H(2)O(2) activated activator protein-1, but not nuclear
      factor kappaB. In addition, H(2)O(2) activated three classes of MAP kinases:
      extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP
      kinase. H(2)O(2) induced alpha(1)(I)procollagen gene expression but did not
      induce proliferation or monocyte chemoattractant protein-1 production. H(2)O(2)
      did not initiate the transformation of freshly isolated PSCs to myofibroblast
      like phenotype. Specific activation of these signal transduction pathways and
      collagen gene expression by H(2)O(2) may play a role in the pathogenesis of
      pancreatic fibrosis.

PMID- 16633732
TI  - Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound
      healing in rats.
AB  - The present investigation was undertaken to determine the efficacy of topical
      administration of flavone of sea buckthorn (Hippophae rhamnoides L.) on cutaneous
      wound healing in rats. Four full-thickness excision wounds were created on the
      back of rat and 1.0% w/v flavone prepared in propylene glycol was applied
      topically. Control animals received the vehicle alone in an identical manner. The
      healing of the wound was assessed by the rate of wound contraction, period of
      epithelialization, hydroxyproline, hexosamine, antioxidants estimation and
      histopathology of the granulation tissue. The sea buckthorn flavone promoted the
      wound healing activity as indicated by improved rate of wound contraction,
      decreased time taken for epithelialization (16.3 days versus 24.8 days in
      controls) and significant increase in hydroxyproline (26.0%) and hexosamine
      (30.0%) content. These findings were also confirmed by histopathological
      examinations. In addition, it was observed that sea buckthorn flavone possesses
      potent antioxidant properties as evidenced by significant increase in reduced
      glutathione (55.0%), vitamin C (70.0%) and catalase (20.0%) activities in wound
      granulation tissue. The flavone treatment also resulted in significant decrease
      in lipid peroxide levels (39.0%). The results suggest that the sea buckthorn
      flavone promotes wound healing activity.

PMID- 16633733
TI  - Real-time monitoring of cAMP response element binding protein signaling in
      porcine granulosa cells modulated by ovarian factors.
AB  - The present study was performed to establish a real-time monitoring of the cAMP
      response element binding protein (CREB) signalling using granulosa cells, and to
      assess the modulation of CREB activity by potential ovarian autocrine/paracrine
      and oocyte-derived factors. Granulosa cells were isolated from porcine follicles
      and cultured for 2 days, and then transfected with CRE-containing pGL3. The cells
      were directly stimulated or cultured with FSH, LH, forskolin, or a permeable cAMP
      analog, and/or IGF-I, EGF, bFGF, TGF-beta2 or TNF-alpha, or cumulus-oocyte
      complex (COCs) for the real-time monitoring of CREB signaling. The activation
      pattern of CREB signaling consisted of three distinct phases, i.e., burst,
      attenuation and refractory. In contrast to FSH, LH, and forskolin, a cAMP analog
      induced the prolonged activation, although three distinct phases were observed at
      its high concentration. Of all the autocrine/paracrine factors, only IGF-I
      slightly induced CREB activity. On the other hand, TGF-beta2 and TNF-alpha
      significantly repressed FSH-stimulated transcriptional activation of CREB by 30%
      (P < 0.05) and 45% (P < 0.05), respectively. Additionally, coculture with COCs
      caused a significant suppression of transcriptional activation of CREB signaling
      stimulated by FSH. These results indicate that ovarian autocrine/paracrine
      factors such as IGF-I, TGF-beta2, TNF-alpha and oocyte-derived factors modulate
      the CREB signaling. The present study provides a new approach for direct
      signaling study on transcription factors under the influences of potential
      factors.

PMID- 16633734
TI  - Functional genomics of PPAR-gamma in human immunomodulatory cells.
AB  - Keeping in view the fact that peroxisome-proliferators activated receptors-PPARs
      (alpha,gamma) play a crucial role in atherogenic inflammation, the present study
      was addressed to explore as to how selective and specific PPAR-gamma gene
      silencing within human mononuclear cells affects genes involved in lipid
      metabolism and innate immune process. Such a study revealed that with respect to
      control cells, the PPAR-gamma knock-out cells exhibited significant reduction in
      the expression of genes coding for PPAR- alpha, CD-36, LDL-R as well as
      significant increase in the expression of genes coding for IL-4, IL-8, IFN-gamma,
      CX3CR1, hTERT. However, the expression of genes coding for LXR-alpha and Receptor
      C( k ) could not be detected in PPAR-gamma knock-out cells. Based on these
      results, we propose that PPAR-gamma gene has the inherent capacity to influence
      the lipid mediated inflammation process in atherosclerotic lesions.

PMID- 16633735
TI  - Remodeling of connexin 43 in the diabetic rat heart.
AB  - In the Streptozotocin-induced diabetic rat heart, a decrease in the conductivity
      and suppression of electrical cell-to-cell coupling were observed. To clarify
      this mechanism, the present study was performed to investigate alterations of the
      gap junction connexin 43 (Cx43) using immunoblotting, immunohistochemistry,
      electron-microscopic analyses. An enhanced activation of PKCepsilon, an
      augmentation of PKCepsilon-mediated phosphorylation of Cx43, a decrease in the
      total amount of Cx43, a reduction in the area of immunoreactive particles for
      Cx43 at the intercalated disk, distribution of Cx43 to cell periphery or
      cytoplasm and the internalization approximately annular profiles of the gap
      junction were all characteristically recognized in the diabetic heart. Such
      abnormalities in the expression of Cx43 were alleviated by treatment with either
      lysosomal (NH(4)Cl, Leupeptin) or proteasomal inhibitor (ALLN). These results
      suggest that the PKCepsilon-mediated hyperphosphorylation of Cx43 makes Cx43
      vulnerable to proteolytic degradation and that a decrease in the conductivity in
      the diabetic heart is also caused by a decrease in the number of gap junction
      channels due to an acceleration of the proteolytic degradation of Cx43. The
      remodeling of Cx43 induced by the activation of PKCepsilon may therefore
      contribute to the formation of the arrhythmogenic substrate in the diabetic
      heart. The cardioprotective effect of the remodeling of Cx43 by PKCepsilon is
      discussed.

PMID- 16633736
TI  - Host cell factor-1 and E2F4 interact via multiple determinants in each protein.
AB  - Host Cell Factor (HCF-1) is a conserved, essential protein initially identified
      as a co-regulator for the Herpes Simplex Virus transactivator VP16. HCF-1 is
      variously involved in regulating transcription, splicing, cell proliferation and
      cytokinesis; however, its mechanisms of action remain unknown. HCF-1 function is
      manifested through an increasing assortment of cellular factors that target
      different regions of the protein. Several HCF-1 partners target the amino
      terminal kelch domain of HCF-1 (residues 1-380) via a consensus HCF-binding motif
      (HBM) comprising the tetrapeptide (D/E)HXY. Searches of sequence databases
      indicated that this motif is present in E2F1 and E2F4, two members of the E2F
      family of cell cycle regulators. We show here that E2F4 specifically and directly
      interacts with HCF-1. Mutational analysis showed E2F4 independently targets the
      kelch domain and the basic domain (residues 450-902) of HCF-1, both of which are
      required for normal cell-cycle progression via separate determinants. The HBM
      containing domain of E2F4 was necessary for interaction with the kelch domain of
      HCF-1 but not for interaction with the basic domain. Mutations in the HCF-1 kelch
      domain known to block cell growth abrogated E2F4 binding to the kelch domain in
      the absence but not in the presence of the juxtaposed basic region. Functionally,
      HCF-1 co-activated E2F4/DP-1 in transient transfection assays, while E2F4 blocked
      HCF-1-dependent rescue of a cell line that harbors a temperature sensitive mutant
      of HCF-1 that causes growth arrest. Our findings show that HCF-1 and E2F4
      interact via multiple determinants and suggest a linkage between E2F4 and HCF-1
      cell growth pathways.

PMID- 16633737
TI  - Opposing action of estrogen receptors alpha and beta on tumor necrosis factor
      alpha gene expression and caspase-8-mediated apoptotic effects in HA22T cells.
AB  - Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer,
      is one of the most frequent and malignant cancers worldwide, especially in
      Taiwan. Estrogen receptors (ERs) have been reported to play either a
      proliferation- or apoptosis-enhancing role in the differentiation of cancers,
      including HCC. In a previous experiment, we showed that transient overexpressed
      estrogen receptor-alpha induced early stage HCC cell line Hep 3B cell apoptosis
      by increasing the hTNF-alpha gene expression in a ligand-independent manner. To
      further clarify if the apoptotic effect occurs in poorly differentiated HCC cell
      line, HA22T, and elucidate the roles of ERs and TNF-alpha, DNA fragmentation and
      caspase activity were measured in late stage HCC cell line, HA22T, by measuring
      the expression of hER-alpha and hER-beta using a Tetracycline-inducible system
      (Tet-on). Increased DNA fragmentation and caspase-3 activity were found in
      hERbeta-overexpressed HA22T cells treated with estrogen (10(-8) M) but not in
      hERalpha-overexpressed HA22T cells. Using RT-PCR/PCR and western blotting in
      HA22T cells, overexpressed hER-beta was also found to increase the expression of
      hTNF-alpha mRNA and induce hTNF-alpha-dependent luciferase activity in a ligand
      dependent manner. Additionally, LPS treatment and hER-beta overexpression both
      enhance caspase-8 activities, whereas neither hER-beta nor E2 treatment affected
      caspase-9 activities. In addition, the overexpressed hER-beta plus E2 enhanced
      DNA fragmentation and caspase-8 activities were only partially reduced by anti
      hTNF-alpha (0.1 ng/ml), which was possibly due to the involvement of P53 and TGF
      beta. Taken together, our data indicates that overexpressed hER-beta but not hER
      alpha may induce caspase-8-mediated apoptosis by increasing the hTNF-alpha gene
      expression in a ligand-dependent manner in poorly differentiated HA22T cells.

PMID- 16633738
TI  - Impact of triphenyltin acetate in microcosms simulating floodplain lakes. II.
      Comparison of species sensitivity distributions between laboratory and semi
      field.
AB  - The study objectives were to shed light on the types of freshwater organism that
      are sensitive to triphenyltin acetate (TPT) and to compare the laboratory and
      microcosm sensitivities of the invertebrate community. The responses of a wide
      array of freshwater taxa (including invertebrates, phytoplankton and macrophytes)
      from acute laboratory Single Species Tests (SST) were compared with the
      concentration-response relationships of aquatic populations in two types of
      freshwater microcosms. Representatives of several taxonomic groups of
      invertebrates, and several phytoplankton and vascular plant species proved to be
      sensitive to TPT, illustrating its diverse modes of toxic action. Statistically
      calculated ecological risk thresholds (HC5 values) based on 96 h laboratory EC50
      values for invertebrates were 1.3 microg/l, while these values on the basis of
      microcosm-Species Sensitivity Distributions (SSD) for invertebrates in sampling
      weeks 2-8 after TPT treatment ranged from 0.2 to 0.6 microg/l based on nominal
      peak concentrations. Responses observed in the microcosms did not differ between
      system types and sampling dates, indicating that ecological threshold levels are
      not affected by different community structures including taxa sensitive to TPT.
      The laboratory-derived invertebrate SSD curve was less sensitive than the curves
      from the microcosms. Possible explanations for the more sensitive field response
      are delayed effects and/or additional chronic exposure via the food chain in the
      microcosms.

PMID- 16633739
TI  - A single amino acid in the RNA-dependent RNA polymerase of Plantago asiatica
      mosaic virus contributes to systemic necrosis.
AB  - From a lily isolate of Plantago asiatica mosaic virus (PlAMV-Li), two sub
      isolates (Li1 and Li6) were obtained. Although the nucleotide sequences of Li1
      and Li6 were highly conserved, they showed different pathogenicity in Nicotiana
      benthamiana. Li1 caused necrosis, whereas Li6 infected the plant
      asymptomatically. Inoculation tests with chimeric and point-mutated viruses
      revealed that amino acid 1154 of the RNA-dependent RNA polymerase (RdRp)
      contributes to the necrotic symptoms. The accumulation of the mutant viruses, in
      which amino acid 1154 of the RdRp was exchanged to the wild-type codon in Li1 and
      Li6, was almost equal.

PMID- 16633740
TI  - Prevalence and social correlates of postnatal depression in a low income country.
AB  - BACKGROUND: Postnatal depression is an important public health problem worldwide.
      Recent evidence suggests that rates may be relatively higher in developing
      countries. We aimed to explore the prevalence of postnatal depression and its
      association with social support and other risk factors in a sample of Pakistani
      women. METHODS: Population-based survey of 149 women at 12 weeks postnatal using
      the Edinburgh Postnatal Depression Scale (EPDS), Multidimensional Scale of
      Perceived Social Support (MSPSS) and Personal Information Questionnaire (PIQ).
      RESULTS: Thirty six percent women scored > or =12 on EPDS. High depression score
      was associated with lower social support, increased stressful life events in the
      preceding year and higher levels of psychological distress in the antenatal
      period. CONCLUSIONS: There is a high prevalence of postnatal depression in
      Pakistani women. Early interventions should be developed that target the
      antenatal period and strengthen social support networks in women at risk.

PMID- 16633742
TI  - Gene therapy strategies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide.
      Effective therapy to this cancer is currently lacking, creating an urgent need
      for new therapeutic strategies for HCC. Gene therapy approach that relies on the
      transduction of cells with genetic materials, such as apoptotic genes, suicide
      genes, genes coding for antiangiogenic factors or immunomodulatory molecules,
      small interfering RNA (siRNA), or oncolytic viral vectors, may provide a
      promising strategy. The aforementioned strategies have been largely evaluated in
      the animal models with HCC or liver metastasis. Due to the diversity of vectors
      and therapeutic genes, being used alone or in combination, gene therapy approach
      may generate great beneficial effects to control the growth of tumors within the
      liver.

PMID- 16633743
TI  - The dawn of surgery in Japan, with special reference to the German society for
      surgery.
AB  - During Japan's period of isolation, Philipp Franz von Siebold came to Nagasaki as
      a doctor with a Dutch trading company in 1823. He used many kinds of apparatus to
      examine patients and taught practices such as paracentesis and tumor resection.
      After the Meiji Restoration, the Japanese government elected to establish a
      medical educational system based on the German system, and to invite two
      prominent German doctors to teach in 1869. In 1881, Julius Karl Scriba came to
      Japan as a teacher. He worked at the University of Tokyo for 25 years. He was the
      clinical coordinator and trained many surgeons who later became leaders in modern
      Japanese surgery. In 1898, Sankichi Sato and Tsugishige Kondo founded the Japan
      Surgical Society. The foundation of the Japan Surgical Society and the
      government's centralization of the University of Tokyo were major milestones,
      because from then on, graduates of the university led the way in surgery in
      Japan. The University of Tokyo has since contributed enormously not only to the
      development of surgery but to the foundation of surgery-related fields.

PMID- 16633744
TI  - The surgical journal of the future: how will it appear?
AB  - Not since the invention of the printing press in 1440 by Johannes Gutenberg has
      there been such a revolution in the methods of dissemination of knowledge as is
      now being seen in the electronic media. The time-honored printed journal is
      becoming obsolete and open-access electronic journals and other technological
      innovations are rapidly reshaping the field of scientific publication. This paper
      will explore some of the forces driving these changes and what lies in store for
      the surgical journal of the future.

PMID- 16633745
TI  - How to write an English medical manuscript that will be published and have
      impact.
AB  - English has become the international language in our world of learning. Yet to
      write a medical manuscript in a second language that is so difficult to master is
      a challenge for many doctors whose native language is not English. My aim is to
      convey that it need not be such a challenge if you follow a few simple rules
      based on the concept of "simplicity = clarity = effective communication." Your
      aim is to publish important research findings and contribute to medical
      advancement; however, your paper will have impact only if the readers can
      understand it easily.

PMID- 16633746
TI  - Creating a manual for proper hand hygiene and its clinical effects.
AB  - PURPOSE: To prevent cross-infections, we created a manual for the treatment of
      infectious wounds that clarifies when to wash one's hands and when to wear
      gloves. METHODS: Six patients with widespread infectious wounds caused by
      methicillin-resistant Staphylococcus aureus (MRSA) were treated. The bacterial
      count on the hands of the staff was calculated. We then compared the number of
      patients with MRSA isolated, and typed the MRSA isolates using pulsed-field gel
      electrophoresis (PFGE). RESULTS: The pathogenic bacterial count among hospital
      staff before treatment/before hand hygiene was 8.2 x 10 colony-forming units
      (cfu)/hand, which were not detected before treatment/after hand hygiene. The
      pathogenic bacterial count on the hands before hand hygiene/after treatment
      climbed to 9.1 x 10(5) cfu/hand, and after treatment/after hand hygiene decreased
      to 0.38 cfu/hand. The number of patients with MRSA isolates before this protocol
      was 15/402 (3.7%), but that level significantly decreased to 5/411 (1.2%) after
      implementation of the manual. There were 13 strains of type F by PFGE before the
      manual was adopted, but five strains of MRSA isolated after the present manual
      was enforced were all observed to have different migration patterns. CONCLUSION:
      A hand hygiene manual is effective for decreasing the rate of cross-infection.

PMID- 16633747
TI  - Arterial embolectomy: a retrospective evaluation of 730 cases over 20 years.
AB  - PURPOSE: We reviewed our experience of treating acute peripheral arterial
      occlusion to determine whether early diagnosis and treatment prevents loss of
      function of the vital organs caused by ischemia threatening the extremities.
      METHODS: We retrospectively examined the records of 730 patients who underwent a
      collective total of 794 operations for peripheral arterial occlusion of the upper
      or lower extremities at Erzurum Numune Hospital between January 1984 and April
      2004. RESULTS: The patients ranged in age from 11 to 86 years old, with a mean
      age of 58.7 years for men and 64.3 years for women. The underlying cause of
      arterial embolism was atrial fibrillation in most (433; 59.3%) patients. Two
      hundred and eleven (28.9%) patients were admitted less than 6 h preoperatively,
      104 (14.2%) were admitted 6-12 h preoperatively, 194 (26.5%) were admitted 12-24
      h preoperatively, and 221 (30.2%) were admitted more than 24 h preoperatively.
      All of the patients underwent embolectomy and 64 revisions were done. The overall
      mortality rate was 3.69%. CONCLUSIONS: The extremity preservation rate was
      related to the time delay between the onset of symptoms and surgical
      intervention.

PMID- 16633748
TI  - Complications of central venous catheters in patients on home parenteral
      nutrition: an analysis of 68 patients over 16 years.
AB  - PURPOSE: To determine the incidence of central venous catheter (CVC)
      complications and to analyze the potential risk factors for complications
      necessitating CVC removal in patients on home parenteral nutrition (HPN).
      METHODS: We studied 68 patients on HPN (44 men and 24 women), examining the
      incidence of CVC complications and CVC-related infections. The risk factors for
      CVC-related infection were investigated using multivariate logistic regression
      analysis. RESULTS: The incidences of CVC complications were 0.29 episodes per CVC
      year in 45 patients with an external tunneled CVC, and 0.66 episodes per CVC-year
      in 23 patients with an implanted port device. The incidences of CVC-related
      infections were 0.17 episodes per CVC-year for external tunneled CVCs and 0.17
      episodes per CVC-year for implanted port devices. There were no significant
      differences in the incidences of CVC complications (P = 0.095), and CVC-related
      infections (P = 0.406). The incidences of CVC-related infections were 0.04
      episodes per CVC-year in 54 patients with malignancies, and 0.68 episodes in 14
      patients with benign diseases (P < 0.001). Multivariate logistic regression
      analysis revealed the types of diseases that influenced the incidence of CVC
      related infections (P < 0.05). CONCLUSIONS: The incidence of CVC complications
      did not differ between the two groups. The type of disease was the most important
      predictive factor of CVC-related infections.

PMID- 16633749
TI  - Preoperative cardiac evaluation: when should the surgeon consult the
      cardiologist?
AB  - PURPOSE: We compiled a manual aimed at reducing preoperative cardiac assessment
      costs and defining the roles of surgeons and cardiologists. We tested
      prospectively and retrospectively if this manual achieved these goals. METHODS:
      Using the Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac
      Surgery of the American College of Cardiology (ACC) / American Heart Association
      (AHA), and other articles as a reference, we compiled the Jichi Medical School
      Hospital (JMSH) Manual in September 2002. This manual contains a novel checklist
      and flowcharts and includes all past and present cardiac disorders,
      complications, abnormalities in electrocardiograms (ECGs) and chest X-rays, and
      evaluation of daily activity. Using this manual, we prospectively studied 1087
      surgical candidates from September 2002 to August 2003, and retrospectively
      analyzed 927 surgical candidates from September 2001 to August 2002. RESULTS: In
      the prospective study, 39 (3.6%) patients were deemed to require further cardiac
      assessment and 4 (0.37%) suffered postoperative complications. In the
      retrospective study, 108 (11.7%) were deemed to require further cardiac
      assessment and 20 (2.2%) suffered postoperative complications. Using this manual
      reduced preoperative cardiac examination costs by 1323,600 Japanese yen,
      representing a 70.5% reduction. CONCLUSIONS: The JMSH Manual defines the roles of
      surgeons and cardiologists and is useful for assessing preoperative cardiac
      function and surgical risks. This manual dramatically reduced the costs
      associated with preoperative cardiac examinations.

PMID- 16633750
TI  - Effect of peritoneal lavage with taurolidine on primary colonic anastomosis in a
      rat model of secondary peritonitis.
AB  - PURPOSE: The reported antibacterial, antiendotoxic, and antiadhesive effects of
      taurolidine prompted us to study the benefits of intraperitoneal lavage with
      taurolidine on primary colonic anastomosis in a rat model of secondary
      peritonitis. METHODS: We induced peritonitis in 40 rats by injecting Escherichia
      coli isolate intraperitoneally. We performed colonic resection and primary
      anastomosis 5 h later, after lavage with either taurolidine or saline solution.
      After the rats were killed, on postoperative day (POD) 3 (n = 10) or 7 (n = 10),
      we measured the bursting pressures and hydroxyproline levels, then examined the
      resected specimens histologically. RESULTS: Bursting pressures and tissue
      hydroxyproline levels were significantly higher in the taurolidine group than in
      the control group on PODs 3 and 7 (P < 0.05). Histopathological examination
      revealed significantly higher fibroblastic activity in the taurolidine group.
      CONCLUSIONS: The higher bursting pressures and tissue hydroxyproline levels in
      the rats given taurolidine showed the positive effect of taurolidine on
      anastomotic strength in secondary peritonitis. Taurolidine is a novel antibiotic
      with both antibacterial and antiendotoxic effects. Intraperitoneal lavage with
      taurolidine solution may reduce the risks associated with performing primary
      colonic anastomosis in patients with secondary peritonitis.

PMID- 16633751
TI  - Long-term functional outcome of colonic J-pouch reconstruction after low anterior
      resection for rectal cancer.
AB  - PURPOSE: To evaluate the long-term functional outcome of colonic J-pouch
      reconstruction after low anterior resection (LAR) for rectal cancer in a
      prospective study. METHODS: We compared the functional outcome of 46 patients who
      underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight
      anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function
      using a 17-item questionnaire about different aspects of bowel function.
      Physiologic reservoir function was evaluated by manovolumetry. RESULTS: Among the
      patients with an ultralow anastomosis (<or=4 cm from the anal verge), those in
      the J-group had fewer bowel movements during the day and at night, and less
      urgency, soiling, protective pad use, incontinence, and dissatisfaction with
      bowel function than those in the S-group. Among the patients with a low
      anastomosis (5-8 cm from the verge), those in the J-group had fewer bowel
      movements at night, and less urgency and soiling than those in the S-group.
      Moreover, reservoir function (reflected by the maximum tolerable volume,
      threshold volume, and compliance) was better in the J-group than in the S-group
      in both the ultralow and low anastomosis groups. CONCLUSION: J-pouch
      reconstruction after low anterior resection creates a better stool reservoir than
      straight anastomosis, especially when the anastomosis is less than 4 cm from the
      anal verge, resulting in a better quality of life 3 years after rectal cancer
      resection.

PMID- 16633753
TI  - Impact of donor age on the growth of young recipient rats after liver
      transplantation.
AB  - PURPOSE: We studied the age-related changes in graft livers, and their impact on
      post-transplantation liver function and the growth of young recipient rats.
      METHODS: Rats aged 11-68 weeks old were studied as controls to assess liver
      histology, liver function, and body weight. We performed orthotopic liver
      transplantation using Kamada's cuff technique without arterial reconstruction.
      Young rats aged 11 weeks were randomized to receive livers from either 11-week
      old donors (YD group) or 52-week-old donors (OD group). Recipient rats were
      killed 0, 8, or 16 weeks after surgery and we assessed the same variables as in
      the controls. RESULTS: We confirmed an age-related increase in the average size
      of hepatocytes and their nuclei. These age-related changes persisted and
      progressed in the graft liver after transplantation. There were no significant
      differences in the levels of serum transaminases or total bilirubin between the
      YD and OD groups, but the serum albumin level was significantly lower in the OD
      group. The YD group grew normally, whereas the OD group recipients lagged
      significantly in gaining body weight. CONCLUSION: We found that 52-week-old
      grafts transplanted into 11-week-old recipients resulted in deficient growth and
      a decline in serum albumin, suggesting that grafted old livers fail to produce
      enough protein to meet the demands of growth adequately.

PMID- 16633752
TI  - The protective effect of alpha-tocopherol and GdCl3 against hepatic
      ischemia/reperfusion injury.
AB  - PURPOSE: To evaluate the combined effect of alpha-tocopherol and gadolinium
      chloride (GdCl3) in reducing lipid peroxidation after severe hepatic
      ischemia/reperfusion (IR) injury. METHODS: Sixty male Wistar rats, 200-250 g,
      were randomly divided into six equal groups. There were two sham operation (SHAM)
      groups, two untreated IR groups, and two IR groups treated with GdCl3 and alpha
      tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min
      reperfusion, one of each group was killed, liver samples were taken for
      malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy
      examination, and blood samples were analyzed for aspartate (AST) and alanine
      (ALT) transaminase, lactate dehydrogenase (LDH), and alpha-tocopherol content.
      The remaining groups were monitored for survival rate determination. RESULTS: The
      mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were
      1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The
      mean alpha-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were
      10.4, 1.9, and 12 micromol/l. The mean serum AST, ALT, and LDH values were
      significantly higher in the IR group than in the SHAM group (P < 0.001), and
      significantly lower in the IRGT group than in the IR group (P < 0.001). Light
      microscopy examination revealed more severe congestion and vacuolization in the
      IR group than in the SHAM group, and minimal congestion and vacuolization in the
      IRGT group. Survival was significantly higher in the IRGT group than in the IR
      group. CONCLUSION: The administration of GdCl3 and alpha-tocopherol is likely to
      protect the liver against lipid peroxidation by suppressing Kupffer cell and
      polymorphonuclear leukocyte activation and enhancing endogenous antioxidant
      activity.

PMID- 16633754
TI  - Tumor thrombectomy without bypass for low-grade malignant tumors extending into
      the inferior vena cava: report of two cases.
AB  - Endometrial stromal sarcoma (ESS) rarely extends into the inferior vena cava
      (IVC). Two cases of ESS extending into the IVC were encountered. In the first
      case a low-grade sarcoma and cavography revealed the tumor thrombus to extend to
      just below the left renal vein from the right internal iliac vein, and the IVC
      was patent. A tumor thrombectomy was accomplished to prevent pulmonary embolism
      (PE) and to achieve a good prognosis. The second case was also a low-grade
      sarcoma. Abdominal computed tomography scanning revealed a large thrombus
      extending into the IVC just below the hepatic vein. A tumor thrombectomy with an
      IVC resection was performed. The postoperative course was uneventful for both
      cases. Aggressive surgical treatment is thus recommended to excise a tumor
      thrombus with or without an IVC resection in patients with ESS of low-grade
      malignancy extending into the IVC to prevent sudden death due to PE.

PMID- 16633755
TI  - Isolated left thoracic isomerism with lung cancer: report of a case.
AB  - Thoracic isomerism, or symmetric morphology, is frequently associated with
      cardiac and abdominal anomalies. We report an unusual case of isolated left
      thoracic isomerism with lung cancer. A 67-year-old woman was referred to our
      hospital for investigation of an abnormal shadow on a chest X-ray. Chest computed
      tomography (CT) showed bilateral hyparterial bronchi, and bronchofiberscopy
      showed bifurcation of the right main bronchus into two branches. Pulmonary
      arteriography subsequently revealed that the right pulmonary artery bifurcated at
      the hilum and that it was not a mirror image of the left pulmonary artery. No
      other malformations were found on echocardiography or abdominal CT scan. We
      performed segmental resection of right S(1+2) and S(3) for lung cancer and the
      patient had an uneventful postoperative course. It is important to clarify the
      anatomy of patients with thoracic isomerism before surgical manipulation.

PMID- 16633756
TI  - Natural killer-like T cell lymphoma of the small intestine: report of a case.
AB  - We report the case of a 77-year-old Japanese man with natural killer (NK)-like T
      cell lymphoma of the small intestine diagnosed after an emergency laparotomy for
      perforated peritonitis. Immunohistochemical staining of the tumor showed that the
      patient had CD3+ CD8+ CD30- CD56+ CD68- CD79a- UCHL-1+ EMA- LMP-1 NK-like T cell
      lymphoma. The patient had a history of hepatocellular carcinoma (HCC) and was
      also diagnosed with T cell non-Hodgkin's lymphoma associated with T cell receptor
      (TCR) reconstruction in the Jgamma chain. Intestinal T cell lymphoma is uncommon
      and very few cases of CD56+ T cell lymphoma, otherwise known as NK-like T cell
      lymphoma, have been reported. The patient did not have a history of gluten
      sensitive enteropathy (celiac disease). Multiple lesions appeared within months
      after the initial operation and his condition deteriorated rapidly. We think that
      this patient probably had NK-type granular lymphocyte-proliferative disorder (NK
      GLPD) because the percentage of CD16+ CD56+ cells among peripheral blood
      mononuclear cells was elevated, at 21%. We report this case to help elucidate the
      relationship between underlying digestive organ disease and the development of
      intestinal NK-like T cell lymphoma. An accumulation of other such cases is needed
      to determine the etiology of this disease.

PMID- 16633757
TI  - Tension pneumothorax secondary to colonic perforation during diagnostic
      colonoscopy: report of a case.
AB  - We report a case of tension pneumothorax, which occurred secondary to colonic
      perforation during a colonoscopy. The patient was a 77-year-old woman in whom
      acute respiratory decompensation developed suddenly during a diagnostic
      colonoscopy for iron deficiency anemia. We diagnosed bilateral pneumothoraces,
      tension pneumothorax, pneumomediastinum, pneumoperitoneum, and emphysema of the
      face, neck, and chest. At laparotomy, a posterior colonic perforation was
      identified at the site of an ileocolic anastomosis performed 3 years earlier. We
      performed a primary repair and the patient was discharged from hospital 12 days
      later. Although diagnostic colonoscopy-induced intestinal perforation is rare, it
      is the most common and serious complication associated with this procedure.
      Occasionally, air spreads from the retroperitoneum into continuous tissue planes
      and decompresses into the adjacent structures. To our knowledge, this is the
      first report of two unique manifestations of diagnostic colonoscopy-induced
      intestinal perforation: tension pneumothorax and perforation at the site of a
      previous anastomosis. Both of these conditions should be considered in the event
      of acute respiratory failure in the endoscopy suite.

PMID- 16633758
TI  - 99mTc-DTPA-galactosyl-human-serum-albumin liver scintigraphy for evaluating
      hepatic functional reserve before hepatectomy in a patient with indocyanine green
      excretory defect: report of a case.
AB  - A 78-year-old woman with indocyanine green (ICG) excretory defect underwent left
      hepatectomy for cystadenocarcinoma. The retention rate of ICG at 15 min
      (ICGR(15)) was high, at 79.3%, despite all other liver function tests showing
      normal values. Conversely, 99mTc-DTPA-galactosyl-human-serum-albumin (GSA) liver
      scintigraphy showed a reduced accumulation of GSA in the left lateral lobe, the
      hepatic uptake ratio of the GSA scintigraphy was 0.96, and the arterial ketone
      body ratio was 1.67. Based on these results, we judged that the hepatic
      functional reserve of this patient was adequate for left hepatectomy, which was
      subsequently performed uneventfully. Histopathological examination of the
      resected liver showed neither fibrosis nor inflammatory cell infiltration. Thus,
      we consider that GSA liver scintigraphy is the best diagnostic modality for
      evaluating hepatic functional reserve in a patient with ICG excretory defect.

PMID- 16633759
TI  - Malignant carcinoid tumor of the common bile duct: report of a case.
AB  - Carcinoid tumors of the extrahepatic bile duct are exceedingly rare and account
      for between 0.1% and 2% of all gastrointestinal carcinoid tumors, with most
      reported cases arising from the gallbladder. We herein present what we believe is
      only the 47th reported case of a primary carcinoid tumor occurring in the
      extrahepatic bile ducts. A 67-year-old woman sought treatment for obstructive
      jaundice accompanied by epigastric pain. Laboratory and imaging studies gave
      results that were consistent with a malignant obstruction in the common bile
      duct. We performed a pylorus-preserving pancreaticoduodenectomy. Pathologically,
      an ill-demarcated mass was noted in the common bile duct measuring 1.6 x 1.5 x
      0.5 cm in size. The tumor had invaded the adjacent pancreatic tissues.
      Immunohistochemically, the mass demonstrated chromogranin, synaptophysin, and
      CD56 positivity. The final pathologic diagnosis was well-differentiated carcinoid
      tumor of a malignant nature. The patient, who underwent a curative surgical
      resection, was alive and disease-free at the time of writing.

PMID- 16633760
TI  - Development of a new surgical gown: a multicenter study.

PMID- 16633762
TI  - Nocturnal episodic hypoxemia after ambulatory breast cancer surgery: comparison
      of sevoflurane and propofol-fentanyl anesthesia.
AB  - PURPOSE: To study the incidence and severity of nocturnal episodic hypoxemia
      after ambulatory breast cancer surgery and its differences with sevoflurane and
      propofol anesthesia. METHODS: Sixty-one adult female patients (ASA PS I-II; age,
      32-77 years) without an apparent history of sleep apnea and respiratory disease
      undergoing major breast cancer surgery on an outpatient basis and with planned
      overnight admission were randomized to one of two anesthesia maintenance groups:
      sevoflurane anesthesia (SEV, n = 31) or intravenous propofol, fentanyl, and
      vecuronium anesthesia (TIVA, n = 30). All patients were administered propofol 2
      mg x kg(-1) intravenously for anesthesia induction, had a laryngeal mask airway
      placed, and received rectal diclofenac and local infiltration anesthesia for pain
      relief. No opioid analgesic or oxygen was administered after discharge from the
      postanesthesia care unit (PACU). Oxygen saturation (Sp(O) (2)) was recorded
      continuously during the first postoperative night. Sp(O) (2) <90% that lasted >10
      s was regarded as hypoxemia, and the percentage of effective recording time with
      Sp(O) (2) <90% (%time with Sp(O) (2) <90) was evaluated. RESULTS: Six patients
      (SEV3/TIVA3) had >1% of %time with Sp(O) (2) <90 (S-hypoxemia group), 17
      (SEV7/TIVA10) had >0% and <or=1% (M-Hypoxemia group), and 38 (SEV21/TIVA17) had
      0% (no-hypoxemia group). There were no statistical differences in age, ASA PS,
      anesthesia technique, and duration of anesthesia among groups. The S-hypoxemia
      group had higher body mass index (BMI) and incidence of oxygen supplementation in
      the PACU than the no-hypoxemia group. No patient had major complications.
      CONCLUSION: Nocturnal episodic hypoxemia occurs frequently after ambulatory
      breast cancer surgery. The incidence was not different between SEV and TIVA.
      Hypoxic patients had a higher BMI and needed oxygen therapy in PACU more
      frequently.

PMID- 16633763
TI  - Effects of propofol vs methohexital on neutrophil function and immune status in
      critically ill patients.
AB  - PURPOSE: Patients with severe brain injury often require long-term sedation and
      have a high incidence of nosocomial infections, causing an increased mortality
      rate. However, whether anesthetic drugs might contribute to immunosuppressive
      effects remains unclear. METHODS: In this prospective study, we investigated the
      effects of propofol (4-6 mg x kg(-1) x h(-1)) and methohexital (1-3 mg x kg(-1) x
      h(-1)) on neutrophil leukocyte function and immune status in 21 patients with
      brain injury who either received propofol (n = 12; 9 male, 3 female; mean age, 51
      +/- 15 years) or methohexital (n = 9; 8 male, 1 female; mean age, 48 +/- 17
      years) after admission to the intensive care unit (ICU). Both sedatives were
      administered over 7 days and individual dosage was adapted according to clinical
      requirements. Neutrophil leukocyte function was assessed as phagocytosis and
      respiratory oxidative burst activity. Furthermore, leukocyte subpopulations, and
      surface markers of lymphocytes and monocytes (CD3; CD4; CD45RO; CD4/CD45RO; CD25;
      CD4 and CD25; CD54; CD69; CD14/HLA-DR; CD8; CD3/HLA-DR; CD4 : CD8 ratio) were
      assessed. Blood samples were drawn on ICU admission, and on days 3, 7, and 14.
      Patients' demographics were compared by Wilcoxon test and laboratory results were
      compared by analysis of variance (ANOVA) for repeated measurements, with an all
      pairwise multiple comparison procedure. RESULTS: There were no significant
      differences in neutrophil oxidative burst and phagocytosis within or between the
      two groups at the different time points. With respect to cellular markers of
      lymphocytes and monocytes, all values throughout remained in the normal range.
      CONCLUSION: Methohexital and propofol exhibited no significant effects on
      neutrophil function and immune status in patients with severe brain injury
      requiring long-term sedation.

PMID- 16633764
TI  - Preoperative administration of intravenous flurbiprofen axetil reduces
      postoperative pain for spinal fusion surgery.
AB  - PURPOSE: The aim of the study was to investigate postoperative analgesia and the
      opioid-sparing effect of the preoperative administration of intravenous
      flurbiprofen axetil in patients undergoing spinal fusion surgery. METHODS: Thirty
      six patients were randomly allocated into one of three groups. Group A received
      preoperative flurbiprofen axetil, 1 mg x kg(-1). Group B received postoperative
      flurbiprofen axetil, 1 mg x kg(-1). Group C received a placebo. All groups were
      given a standardized anesthesia and intravenous morphine via a patient-controlled
      analgesia device for postoperative analgesia. The pain score was evaluated by a
      visual analog scale (VAS) at 0 (T(0)), 1 (T(1)), 2 (T(2)), 6 (T(3)), 12 (T(4)),
      and 24 (T(5)) h after surgery, and the morphine requirement was recorded during
      the study period. RESULTS: VAS in group A was significantly lower than that in
      group B at T(0) and T(1). VAS in group A was significantly lower than that in
      group C throughout the time course after surgery. Postoperative morphine
      consumption in group A was significantly lower than that in groups B and C at
      T(0) to T(3). CONCLUSION: As compared with postoperative administration,
      preoperative administration of intravenous flurbiprofen axetil provides better
      postoperative analgesia and an opioid-sparing effect in patients undergoing
      spinal fusion surgery under general anesthesia.

PMID- 16633765
TI  - Effect of peak inspiratory flow on gas exchange, pulmonary mechanics, and lung
      histology in rabbits with injured lungs.
AB  - PURPOSE: The aim of this study was to evaluate, using a rabbit model, the little
      known effect of different levels of peak inspiratory flow on acutely injured
      lungs. METHODS: Fourteen male rabbits (body weight, 2,711 +/- 146 g) were
      anesthetized and their lungs were injured by alveolar overstretch with mechanical
      ventilation until Pa(O(2)) was reduced below 300 mmHg. Injured animals were
      randomly assigned to: the P group-to receive pressure-regulated volume-control
      ventilation (PRVCV; n = 7); and the V group-to receive volume-control ventilation
      (VCV; n = 7). Other ventilator settings were: fraction of inspired oxygen
      (FI(O(2)), 1.0; tidal volume, 20 ml x kg(-1); positive end-expiratory pressure
      (PEEP) 5 cmH(2)O; and respiratory rate, 20 min(-1). The animals were thus
      ventilated for 4 h. Throughout the protocol, ventilatory parameters and blood gas
      were measured every 30 min. After the protocol, the lung wet-to-dry ratio and
      histological lung injury score were evaluated in the excised lungs. RESULTS:
      Throughout the protocol, peak inspiratory flow and mean inspiratory flow values
      in the P group were significantly higher than those in the V group (26.7 +/- 5.0
      l x min(-1) vs 1.2 +/- 0.2 l x min(-1), and 4.3 +/- 0.3 l x min(-1) vs 1.1 +/-
      0.1 l x min(-1); P < 0.05). The wet-to-dry ratio in the P group was also
      significantly higher than that in the V group (7.7 +/- 0.9 vs 6.3 +/- 0.5; P <
      0.05). More animals in the P group than in the V group had end-of-protocol
      Pa(O(2))/FI(O(2)) ratios below 200 mmHg (43% vs 0%; P = 0.06). CONCLUSION: In
      rabbits with injured lungs, high peak inspiratory flow with high tidal volume
      (V(T)) reduces the Pa(O(2))/FI(O(2)) ratio and increases the lung wet-to-dry
      ratio.

PMID- 16633766
TI  - Two cases of spinal epidural abscess with granulation tissue associated with
      epidural catheterization.
AB  - Two cases of spinal epidural abscess are reported whose abscesses became
      granulated after epidural catheterization. Although emergency surgical
      intervention was performed almost within 24 h after the diagnosis of epidural
      abscess in case 1, the patient revealed a poor outcome. After laminoplasty, case
      2 received lumbar epidural catheterization, and he had a complete recovery. The
      abscesses were recognized to spread around the catheter insertion site of the
      operative procedure in both cases, and MRI in case 2 showed the connection
      between the epidural abscess and the interspinous space where the catheter had
      been inserted. Methicillin-sensitive Staphylococcus aureus (MSSA) was identified
      at the operative field in both cases. Also, MSSA was identified at the
      subcutaneous abscess around the catheter in case 1 and at the catheter tip in
      case 2. Those findings suggest the midpoint of the abscess is the puncture site
      and that MSSA is found in or around the catheter. Infection at epidural
      catheterization seems to be caused by catheter insertion or skin contamination
      after catheterization. As those catheterizations were completed in the outpatient
      theater, we conclude that epidural catheterization should be performed in the
      operating room or with a restricted aseptic technique.

PMID- 16633767
TI  - Postextubation airway management with nasal continuous positive airway pressure
      in a child with Down syndrome.
AB  - We describe our experience with use of variable-flow nasal continuous positive
      airway pressure (NCPAP) to manage postextubation stridor in a 31-month-old child
      with Down syndrome (DS). Although it has been recognized that children with DS
      tend to develop obstruction of the upper airway postoperatively, little is known
      concerning appropriate management of this situation. Although there are
      surprisingly few reports of use of variable-flow NCPAP for children older than
      preterm infants, we successfully treated postextubation ventilatory complications
      by providing variable-flow NCPAP without complications such as pneumothorax.

PMID- 16633768
TI  - Effects of lumbar sympathetic ganglion block for a patient with amyotrophic
      lateral sclerosis (ALS).
AB  - A 59-year-old man with amyotrophic lateral sclerosis (ALS) received lumbar
      epidural and sympathetic ganglion blocks to increase regional blood flow and
      improve his clinical symptoms. After a lumbar epidural block (0.5% mepivacaine),
      the skin temperature of his affected lower extremities rose by 7.0 degrees C and
      became close to that of the intact side, and the distance he was able to walk
      with his cane increased from 2 to 8 m. The clinical effects produced by the
      lumbar sympathetic ganglion block (99.5% alcohol) were sustained for
      approximately 8 weeks after the first block and for approximately 6 weeks after
      the second block. There were no particular adverse effects or complications
      associated with these nerve block procedures. Epidural and sympathetic ganglion
      blocks for an ALS patient, albeit their effects are of a transient nature, may
      improve related clinical symptoms, and were thought to play a contributory role
      in improving our patient's quality of life.

PMID- 16633769
TI  - Perioperative management for placement of tracheobronchial stents.
AB  - Tracheobronchial stenting was performed under general anesthesia, with (six
      patients) or without (two patients) muscle relaxant, in eight patients suffering
      from carcinoma. All patients had presented preoperatively with dyspnea,
      exhibiting Hugh-Jones grade 4 or 5. Three patients had been mechanically
      ventilated before the procedure. The procedure was performed under general
      anesthesia with flexible bronchoscopic guidance. Stent placement was performed
      either through an orotracheal tube (four patients) or through a transtracheal
      tube (two patients) in those who had no upper tracheal stenosis, while it was
      performed through a laryngeal mask airway in two patients with upper tracheal
      stenosis. During the procedure, arterial hemoglobin oxygen saturation (Sp(O(2))
      decreased in all patients, despite fraction of inspired oxygen (FI(O(2)) being
      maintained at 1.0. Except for two patients, one of whom developed superior vena
      cava syndrome and one, tension pneumothorax after stent placement, there were no
      complications resulting from stent placement. Six patients were weaned from
      mechanical ventilation (0-24 days after the procedure). Two of the three patients
      who had been on mechanical ventilation preoperatively could not be weaned. Stent
      insertion is an effective treatment for tracheobronchial stenosis, but its
      indications in patients with malignancy who have been mechanically ventilated
      prior to stenting should further be evaluated.

PMID- 16633770
TI  - Aberrant halt of syringe pump motion: an improved system to prevent false setting
      of the syringe.
AB  - A syringe pump is used to inject precise doses of drugs having a strong action;
      for example, vasoactive drugs. Unexpected and undetected halt of a syringe pump
      can lead to potentially life-threatening complications. We experienced a sudden
      halt in the movement of a syringe pump (Terufusion syringe pump; Terumo, Tokyo,
      Japan) in two patients while administering norepinephrine in the intensive care
      unit (ICU). Fortunately, the patients had only transient hypotension, which was
      immediately detected and promptly treated, without any untoward sequelae. As a
      result of the occurrence of such cases, we conducted a detailed investigation of
      the causes of this sudden halt in the syringe pump. We could not reproduce the
      aberration of the syringe pump and thus could not specify the cause in the first
      patient. In the second patient, however, a false setting on the syringe was
      suspected to be the cause of the problem. In order to prove this, we tried to
      reproduce the situation where a syringe pump, due to a false syringe setting,
      abruptly terminated while giving a "syringe loss" warning, after a period of
      precise functioning. Once we had determined how a false setting of the syringe
      could occur without the syringe pump giving off an alarm from the onset, we
      collaborated with the Terumo Company to revise their current instruction manual
      to incorporate this as a warning. We also helped in the development of a new
      model, including a new safety feature that would prevent a false setting of the
      syringe from occurring at all. This new model was released in December 2003.

PMID- 16633771
TI  - Inadvertent intrathecal cannulation in an infant, demonstrated by three
      dimensional computed tomography: a rare complication of internal jugular vein
      catheterization.
AB  - We describe a case of inadvertent intrathecal cannulation with a central venous
      catheter in an infant, confirmed by three-dimensional computed tomography, which
      clearly demonstrated the track of the catheter. We believe that this complication
      could have been related to two major factors: depth of needle insertion and
      penetration of the vein by a straight-tip guidewire. To avoid this complication,
      the depth of needle insertion must be carefully checked, a "J"-tipped rather than
      a straight-tipped guidewire should be used, and puncture should be guided by
      ultrasound.

PMID- 16633772
TI  - Syndrome of inappropriate secretion of antidiuretic hormone associated with
      paroxetine.
AB  - A 71-year old man with failed back syndrome was admitted to hospital with
      oliguria that had occurred 4 days after his dose of paroxetine had been increased
      to 40 mg x day(-1). Laboratory data on admission revealed hyponatremia (124 mmol
      x l(-1)), low serum osmolarity (267 mOsm x l(-1)) with a normal level of serum
      antidiuretic hormone (1.7 pg x ml(-1)), and concentrated urine (430 mOsm x l(
      1)). He was diagnosed as having syndrome of inappropriate secretion of
      antidiuretic hormone, associated with paroxetine; this drug was discontinued
      immediately after admission. The hyponatremia was treated with saline infusion,
      water restriction, and furosemide; serum sodium level returned to normal on
      hospital day 5. Paroxetine is being increasingly used for depression and chronic
      pain management because of its favorable side-effect profile; however, we should
      be alert to hyponatremia in patients on paroxetine by carrying out periodic
      monitoring of serum electrolytes, especially in elderly patients.

PMID- 16633773
TI  - The use of continuous hemodiafiltration in a patient with diabetic ketoacidosis.
AB  - A variety of fatal complications are associated with diabetes mellitus. Among
      these, diabetic ketoacidosis (DKA) figures largely in fatalities in young
      diabetics. Although hyperosmotic diuresis in DKA causes extreme fluid loss, acute
      renal failure is less common than expected in DKA. We treated a case of severe
      DKA with associated coma, acute respiratory failure, and acute renal failure in a
      24-year-old man who had been diagnosed with type 1 diabetes mellitus at age 19.
      The comatose patient had been intubated before transfer to our hospital for
      intensive care. Despite infusion with isotonic saline and insulin, metabolic
      acidosis was refractory. On day 2, urine output decreased and pulmonary
      congestion developed, so we started continuous veno-venous hemodiafiltration
      (CVVHDF), which was effective against the metabolic acidosis; urine output
      increased gradually. CVVHDF was withdrawn on day 7, and the patient's renal
      function recovered completely. He was discharged from the intensive care unit
      (ICU) on day 14.

PMID- 16633774
TI  - Changes on MRI in lumbar disc protrusions in two patients after intradiscal
      electrothermal therapy.
AB  - We examined changes to the protruded lumbar disc after intradiscal electrothermal
      therapy (IDET) using magnetic resonance imaging (MRI) in two patients with
      chronic discogenic low back pain who underwent IDET. MRI was performed before and
      6 months after the treatments. In the follow-up MRI studies, the protrusions were
      almost abolished and normalized in both patients. We thus confirmed shrinkage of
      the protruded disc by IDET on MRI images in two patients.

PMID- 16633775
TI  - Anesthetic management of a pediatric patient on a ketogenic diet.
AB  - There are several specific considerations regarding seizure control during the
      perioperative period in patients who have been placed on a ketogenic diet (KD). A
      KD is high in fat and low in protein and carbohydrates and has a long history of
      use for the treatment of intractable seizures in children. Maintaining
      therapeutic ketosis and modifying the acid-base balance are particularly
      important for preventing seizures in patients on a KD. We report changes in the
      biochemical parameters of a patient with double cortex syndrome who was on a KD
      and who had been scheduled for the treatment of dental caries under sevoflurane
      anesthesia and acetate Ringer administration. Inhalation induction with a high
      concentration of sevoflurane should be reconsidered in view of recent reports
      describing the epileptogenic potential of sevoflurane.

PMID- 16633776
TI  - General anesthesia in a patient with dystrophic epidermolysis bullosa.
AB  - A 13-year-old boy with epidermolysis bullosa underwent a repair of
      pseudosyndactyly. He had a long history of bullae formation in the oral cavity
      and on the pharynx and body surface, and some were active at the time of surgery.
      We chose inhalational general anesthesia with tracheal intubation using
      sevoflurane and nitrous oxide. The trachea was successfully extubated after the
      surgery, and no major bulla formation was observed. General anesthesia with
      tracheal intubation may be chosen as anesthesia for patients with epidermolysis
      bullosa.

PMID- 16633777
TI  - Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury
      in rats.
AB  - We tested the effect of Ono-EI-600, an elastase inhibitor that suppresses
      cytokine release, on ventilator-induced lung injury in a rat model. After Wistar
      rats (aged 8-11 weeks) were anesthetized and tracheostomized, they were randomly
      assigned to four groups: high tidal volume (V(T)) group (H group: n = 10)
      receiving peak inspiratory pressure (PIP) 30 cmH(2)O for 240 min; high V(T) with
      drug group (HD group: n = 10) receiving the same ventilation settings as H group
      and also intravenous infusion 10 mg x kg(-1) x h(-1) of Ono-EI-600 during the
      protocol; the lower V(T) group (L group: n = 5) receiving PIP 10 cmH(2)O for 240
      min; and control group (C group: n = 5) receiving the same ventilation as L group
      for 30 min. The cytokine levels (IL-6 and CINC-1) in the bronchoalveolar lavage
      fluid (BALF) of the H group were significantly higher than those of the C and L
      groups (P < 0.05). However, for the H and HD groups, no differences were found in
      arterial blood gas data, cytokine levels in BALF, and histological injury scores.
      Our experiment provided no evidence that elastase inhibitor Ono-EI-600 protects
      against lung injury induced by high V(T) ventilation.

PMID- 16633778
TI  - Preferable inotropic action of procaterol, a potent bronchodilator, on impaired
      diaphragmatic contractility in an intraabdominal septic model.
AB  - Intraabdominal sepsis can lead to acute respiratory failure, and concomitant
      diaphragmatic dysfunction may be aggravated by sepsis-induced airway
      hyperreactivity. We previously reported that isoproterenol, a nonselective beta
      adrenoceptor agonist, increased diaphragmatic contractility and accelerated
      recovery from fatigue during sepsis. The purpose of this study was to demonstrate
      the direct inotropic effect of a potent bronchodilator and beta(2)-selective
      adrenoceptor agonist, procaterol, on fatigued diaphragmatic contractility in an
      intraabdominal septic model. Rats were divided into two groups: a cecal ligation
      and perforation (CLP) group and a sham group. CLP was performed in the CLP group
      whereas laparotomy alone was performed in the sham group. The left hemidiaphragm
      was removed at 16 h after the operation. The diaphragmatic tissues were exposed
      to procaterol (10(-8)-10(-6) M), and muscle contractility was assessed.
      Intracellular cyclic AMP levels were also measured in the CLP model. Procaterol
      caused an upward shift in the force-frequency curves in the CLP group whereas it
      had no effect on the curves in the sham group. Procaterol significantly increased
      cyclic AMP levels in the CLP model. We conclude that the potent bronchodilator
      procaterol had a direct and positive inotropic effect on the diaphragm in an
      intraabdominal septic model.

PMID- 16633779
TI  - Bispectral index-guided desflurane and propofol anesthesia in ambulatory
      arthroscopy: comparison of recovery and discharge profiles.
AB  - In this prospective, randomized study we compared the recovery profiles of
      bispectral index (BIS)-guided anesthesia regimens with desflurane or propofol in
      ambulatory arthroscopy. Fifty ASA I-II adult patients who underwent knee
      arthroscopy were randomized to receive desflurane (D) or propofol (P) infusion
      accompanied by remifentanil and nitrous oxide during maintenance, titrated to
      maintain a bispectral index value between 50 and 60. Initial awakening, fast
      track eligibility, and home readiness as well as intraoperative hemodynamics,
      were compared. The groups did not differ with respect to demographics, duration
      of operation, or intraoperative vital signs. Although the times for initial
      awakening parameters were shorter in group D, the differences between the groups
      were not significant. The time needed for the White fast-track score to reach 12
      was shorter in group P than group D (9 +/- 3.5 min vs 12.5 +/- 5.3 min). However,
      home readiness did not differ significantly between the groups. Desflurane is an
      alternative to propofol for BIS-guided ambulatory anesthesia. Using desflurane in
      combination with opioid analgesics blunted its rapid emergence characteristics,
      and the higher frequency of emetic symptoms with desflurane diminished the
      success of its fast-track eligibility.

PMID- 16633780
TI  - Effect-compartment equilibrium rate constant (keo) for propofol during induction
      of anesthesia with a target-controlled infusion device.
AB  - The effect-compartment concentration (C(e)) of a drug at a specific
      pharmacodynamic endpoint should be independent of the rate of drug injection. We
      used this assumption to derive an effect-compartment equilibrium rate constant
      (k(eo)) for propofol during induction of anesthesia, using a target controlled
      infusion device (Diprifusor). Eighteen unpremedicated patients were induced with
      a target blood propofol concentration of 5 microg x ml(-1) (group 1), while
      another 18 were induced with a target concentration of 6 microg x ml(-1) (group
      2). The time at loss of the eyelash reflex was recorded. Computer simulation was
      used to derive the rate constant (k(eo)) that resulted in the mean C(e) at loss
      of the eyelash reflex in group 1 being equal to that in group 2. Using this
      population technique, we found the k(eo) to be 0.57 min(-1). The mean (SD) effect
      compartment concentration at loss of the eyelash reflex was 2.39 (0.70) microg x
      ml(-1). This means that to achieve a desired C(e) within 3 min of induction, the
      initial target blood concentration should be set at 1.67 times that of the
      desired C(e) for 1 min, after which it should revert to the desired
      concentration.

PMID- 16633781
TI  - Syncope after therapeutic caudal epidural block: report of two cases.

PMID- 16633782
TI  - Epidural anesthesia for cesarean delivery in a parturient with a double-outlet
      right ventricle.

PMID- 16633784
TI  - Histopathology reporting of prostate needle biopsies. 2005 update.
AB  - This report reviews the diagnostic and prognostic importance of the pathologic
      findings in prostate needle biopsies. The morphological findings of the needle
      biopsy may be placed into one of the following five categories: prostate cancer,
      atypical small acinar proliferation, high-grade prostatic intraepithelial
      neoplasia, inflammation, and benign prostatic tissue. While the prime goal of the
      biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected,
      further descriptive information regarding the type, amount of cancer, and grade
      forms the cornerstone for contemporary management of the patient and for
      assessment of the potential for local cure and the risk for distant metastasis.
      The information provided in the needle biopsy report regarding the attributes of
      carcinoma is used depending on the individual patient's medical condition and
      preference and on the treating physician's evaluation to determine whether any
      form of treatment is indicated and, if so, the type of therapy.

PMID- 16633785
TI  - Peripheral T-cell lymphoma with involvement of the expanded mantle zone.
AB  - Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently,
      two variants have been described with infiltration of the B-cell follicle, one
      variant that localizes to the marginal zone with a so-called perifollicular
      growth pattern, and a variant that localizes to the germinal center. These
      lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five
      similar cases of PTCL with involvement of the B-cell follicle. However, our cases
      differ from the cases previously described by their predominant and frequently
      patchy involvement of the expanded mantle zone of the B-cell follicle at onset.
      Later biopsies in three of the cases show diffuse infiltration of the lymph node,
      without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in
      addition to CD4. Cytogenetics was available in four of the cases but revealed no
      recurrent chromosomal aberrations or changes associated with other types of PTCL.
      No mutations of the BCL-6 gene were observed. Together, the cases seem to have an
      intermediately aggressive clinical behavior. Whether our cases are part of a
      spectrum of PTCLs that encompasses previously described variants with predominant
      marginal zone or germinal center infiltration or they represent a separate T-cell
      lymphoma type remains to be demonstrated by a study of more of such cases.

PMID- 16633786
TI  - Real-time dynamics of label-free single mast cell granules revealed by
      differential interference contrast microscopy.
AB  - We demonstrate the capability of differential interference contrast (DIC)
      microscopy as a simple and useful tool for studying cellular events without
      fluorescence labeling. By coupling an advanced DIC microscope to a computer
      controlled motorized vertical stage and a high-speed, high-resolution CCD camera,
      real-time three-dimensional monitoring is possible in a high-throughput manner.
      The performance among three modes of microscopy, bright-field, dark-field and
      DIC, in terms of horizontal resolving power and vertical sectioning was
      investigated. As a model, exocytosis of rat peritoneal mast cells was recorded on
      the subsecond time scale. Three-dimensional tracking of granules during
      degranulation was achieved and granule-granule fusion before plasma membrane
      fusion was recorded.

PMID- 16633788
TI  - Renewable stationary phase liquid magnetochromatography: determining aspartame
      and its hydrolysis products in diet soft drinks.
AB  - A new chromatographic modality that does not require high pressures and also
      allows renewal of the stationary phase as desired is reported. The technique is
      based on a thin layer paramagnetic stationary phase (Fe3O4-SiO2) retained on the
      inner wall of a minicolumn through the action of an external magnetic field,
      which also plays an important role in separating the analytes. Accordingly, the
      name "renewable stationary phase liquid magnetochromatography", or RSP-LMC, has
      been proposed for it. The technique was used to separate and quantify the sugar
      substitute alpha-aspartame and its constituent amino acids (hydrolysis products),
      L-aspartic acid and L-phenylalanine, in diet fizzy soft drinks. When the results
      obtained for alpha-aspartame were compared with those obtained using HPLC as a
      reference method, no significant differences were observed. The system proposed
      is fully automated, making it an economic, competitive alternative to
      conventional methods of determining alpha-aspartame and its amino acid
      components.

PMID- 16633789
TI  - Dual breath-hold magnetic resonance cine evaluation of global and regional
      cardiac function.
AB  - The purpose of our study was to evaluate the accuracy of a multislice cine
      magnetic resonance imaging (MRI) technique with parallel imaging in regard to
      global and regional left ventricular function. Forty-two individuals underwent
      cine MRI on a 1.5-tesla scanner. Cine MRI used a steady-state free precession
      technique and was performed as a single-slice technique (nonTSENSE cine) and an
      accelerated multislice technique (TSENSE cine) with five slices per breath-hold.
      End diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF)
      were evaluated for all data sets and in regard to regional wall motion and
      regional wall motion analysis, and quantitative regional wall thickness and
      systolic thickening were also assessed. EDV, ESV, and EF based on TSENSE cine
      showed excellent correlation to the nonTSENSE cine approach (all r(2)=0.99,
      P<0.001). While EDV evaluations showed a small underestimation for TSENSE cine,
      ESV and EF showed accurate results compared with nonTSENSE cine. Both readers
      showed good agreement (kappa=0.72) in regional wall motion assessment comparing
      both techniques. Data acquisition for the multislice approach was significantly
      shorter ( approximately 75%) that in single-slice cine. We conclude that accurate
      evaluation of regional wall motion and left ventricular EF is possible using
      accelerated multislice cine MR with high spatial and temporal resolution.

PMID- 16633790
TI  - MR imaging in sports-related glenohumeral instability.
AB  - Sports-related shoulder pain and injuries represent a common problem. In this
      context, glenohumeral instability is currently believed to play a central role
      either as a recognized or as an unrecognized condition. Shoulder instabilities
      can roughly be divided into traumatic, atraumatic, and microtraumatic
      glenohumeral instabilities. In athletes, atraumatic and microtraumatic
      instabilities can lead to secondary impingement syndromes and chronic damage to
      intraarticular structures. Magnetic resonance (MR) arthrography is superior to
      conventional MR imaging in the diagnosis of labro-ligamentous injuries, intrinsic
      impingement, and SLAP (superior labral anteroposterior) lesions, and thus
      represents the most informative imaging modality in the overall assessment of
      glenohumeral instability. This article reviews the imaging criteria for the
      detection and classification of instability-related injuries in athletes with
      special emphasis on the influence of MR findings on therapeutic decisions.

PMID- 16633791
TI  - Dosimetric characteristics of a 16-slice computed tomography scanner.
AB  - Standard CT dose measurements were performed on a Siemens Sensation 16 scanner.
      CT dose indices, free-in-air (CTDI(F)) and weighted (CTDI(W)), were measured in
      all available axial and helical beam collimations of the head and body scanning
      modes. The effect of tube current, high voltage, rotation time, beam collimation
      and pitch on the CT doses was investigated. CT doses increased as a power
      function of high voltage. The kVp exponent n varied with beam collimation from
      2.7 to 3.1 for CTDI(W), and from 2.4 to 2.6 for CTDI(F). Automatic change of the
      focal spot size increased radiation doses up to a factor of 1.18. Measured small
      focus CTDI(W) values differed from those displayed at the console from -24 to
      14%. Peripheral doses in the head phantom were higher compared to the body
      phantom by a factor of 1.5 to 2. Central doses are 2.7 to 4.1 times higher.
      Differences in beam collimation resulted in 50% variation in the CTDI(W) in the
      body phantom and 60% in the head phantom. In conclusion, our study has confirmed
      the great impact of technique factors and acquisition parameters on CT doses. The
      provided comprehensive dosimetric data will facilitate the dose-effective use of
      the scanner studied.

PMID- 16633792
TI  - Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to
      bedside.
AB  - This review paper presents, in the first part, the different classes of contrast
      media that are already used or are in development for cardiac magnetic resonance
      imaging. A classification of the different types of contrast media is proposed
      based on the distribution of the compounds in the body, their type of relaxivity
      and their potential affinity to particular molecules. In the second part, the
      different uses of the extracellular type of T1-enhancing contrast agent for
      myocardial imaging is covered from the detection of stable coronary artery
      disease to the detection and characterization of chronic infarction. A particular
      emphasis is placed on the clinical use of gadolinium-chelates, which are the
      universally used type of MRI contrast agent in the clinical routine. Both
      approaches, first-pass magnetic resonance imaging (FP-MRI) as well as delayed
      enhanced magnetic resonance imaging (DE-MRI), are covered in the different
      situations of acute and chronic myocardial infarction.

PMID- 16633796
TI  - Posterior segment injury developed after injection of anesthetics on eyelids with
      needleless jet injection device.
AB  - BACKGROUND: Though a needleless jet injection device (NJI device) has advantages
      over a conventional needle attached syringe for injecting anesthetics, safety of
      using it for lid surgery is not proved. We report a case of posterior segment
      injury suspected caused by a NJI device. METHODS: A 47-year-old woman presented
      with decreased visual acuity after regional anesthesia at the lower eyelids with
      a NJI device. RESULTS: Vitreous and subretinal hemorrhage was found associated
      with retinal edema adjacent to the optic disc of the right eye and around the
      inferior temporal arcade of the left eye. Fluorescein angiography revealed
      choroidal rupture in the both eyes. By 2 months, although the hemorrhage
      resolved, subretinal fibrosis and chorioretinal atrophy developed. Her vision
      decreased to 20/60 in the right eye and 20/40 in the left eye. CONCLUSION: The
      energy generated by the NJI device seemed to have reached the eyeballs to cause
      the blunt-typed posterior segment injuries. As choroidal rupture may result in a
      permanent visual loss, the risks associated the off-labeled use of the device for
      lid surgeries should be awakened.

PMID- 16633797
TI  - Endothelial nitric oxide synthase gene polymorphisms in non-arteritic anterior
      ischemic optic neuropathy.
AB  - BACKGROUND: To examine the association between the polymorphisms of the
      endothelial nitric oxide synthase (eNOS) gene and the occurrence of non-arteritic
      anterior ischemic optic neuropathy (NAION). METHODS: We studied 15 patients with
      NAION (mean age, 62 years; 60% male). We investigated two polymorphisms of the
      eNOS gene, Glu298Asp polymorphism of exon 7 and T(-786)C polymorphism of the
      promoter region. The genotype distribution in NAION was compared with the control
      (mean age, 63 years; 63% male) distribution. RESULTS: There was no significant
      difference in the genotype distribution of the Glu298Asp polymorphism between the
      NAION and control groups (P = 1.000), whereas the genotype dis-tribution of the
      T(-786)C polymorphism varied significantly between the patients with NAION and
      control subjects (P = 0.002). After adjusting on covariates, individuals with the
      CC genotype of the T(-786)C polymorphism were more likely to develop NAION
      compared with those with TT genotype (odds ratio = 0.09: 95% CI 0.01-0.86).
      CONCLUSIONS: We found an increased prevalence of T(-786)C polymorphism of the
      eNOS gene in patients with NAION. Our data suggest that the T(-786)C polymorphism
      of the eNOS gene may be an important risk factor in the development of NAION in
      Japanese subjects.

PMID- 16633798
TI  - Effects of midazolam on explicit vs implicit memory in a pediatric surgery
      setting.
AB  - RATIONALE: Placebo-controlled studies show that midazolam impairs explicit memory
      in children undergoing surgery (Buffett-Jerrott et al., Psychopharmacology
      168:377-386, 2003; Kain et al., Anesthesiology 93:676-684, 2000). A recent within
      subjects study showed that midazolam impaired explicit memory while leaving
      implicit memory intact in a sample of older children undergoing painful medical
      procedures (Pringle et al., Health Psychol 22:263-269, 2003). OBJECTIVES: We
      attempted to replicate and extend these findings in a randomized, placebo
      controlled design with younger children undergoing surgery. MATERIALS AND
      METHODS: Children aged 3-6 years who were undergoing ear tube (myringotomy)
      surgery were randomly assigned to receive midazolam (n = 12) or placebo (n = 11).
      After surgery, they were tested on explicit (recognition) and implicit (priming)
      memory for pictures encoded before surgery. RESULTS: Relative to placebo, the
      midazolam-treated children showed poorer recognition memory on the explicit task
      but equivalent priming on the implicit task. CONCLUSIONS: Overall, it appears
      that midazolam induces a dissociation between explicit and implicit memory in
      young children in the pediatric surgery setting. Theoretical and clinical
      implications of the findings are discussed along with directions for future
      research.

PMID- 16633803
TI  - An inverse agonist selective for alpha5 subunit-containing GABAA receptors
      improves encoding and recall but not consolidation in the Morris water maze.
AB  - RATIONALE: Compounds selective for the GABAA receptors containing an alpha5
      subunit have been reported to enhance performance in the hippocampally mediated
      delayed-matching-to-position version of the Morris water maze, in which reduction
      in the time required to find a hidden platform relative to an initial trial is
      used as an index of learning and memory. OBJECTIVE: In the present study, we have
      used one such compound, alpha5IA-II, to examine whether these effects occur
      during the encoding, consolidation or recall phases of this paradigm. METHODS:
      alpha5IA-II was administered in the absence or presence of the benzodiazepine
      site antagonist flumazenil, so as to limit its action to periods associated with
      encoding, consolidation and recall. Drug doses and timings of administrations
      were defined using occupancy data derived from an in vivo [3H]flumazenil binding
      assay. Similar experiments were carried out to study the memory-disruptive
      properties of chlordiazepoxide (CDP). RESULTS: The trial 1 to trial 2 difference
      was increased when alpha5IA-II was given before either trial 1 or trial 2,
      indicating an effect on the encoding and recall phases, respectively, of learning
      and memory. Conversely, alpha5IA-II had no effect on performance when given
      immediately after trial 1, suggesting that it had no effect on the consolidation
      phase. In contrast to the facilitation of performance produced by the alpha5
      selective inverse agonist alpha5IA-II given during the encoding and recall but
      not the consolidation phase, the non-selective agonist CDP impaired performance
      when given during the encoding and recall phases, whilst having no effect on the
      consolidation phase. CONCLUSIONS: These data further highlight the cognition
      enhancing properties of GABAA alpha5-selective inverse agonists and define the
      functional specificity of these effects in terms of encoding and recall processes
      in the Morris water maze.

PMID- 16633806
TI  - Growth hormone replacement in hypophysectomized rats affects spatial performance
      and hippocampal levels of NMDA receptor subunit and PSD-95 gene transcript
      levels.
AB  - Clinical studies have demonstrated that growth hormone (GH) promotes learning and
      memory processes in GH-deficient (GHD) patients. In animal studies, GH also
      influences the N-methyl-D-aspartate (NMDA) receptor system in the hippocampus, an
      essential component of long-term potentiation (LTP), which is highly involved in
      memory acquisition. This study was designed to examine the beneficial effects of
      recombinant human GH (rhGH) on cognitive function in male rats with multiple
      hormone deficiencies resulting from hypophysectomy (Hx). The performance of an
      rhGH-treated group and an untreated control group was appraised in the Morris
      water maze (MWM). The rhGH-treated group performed significantly better in the
      spatial memory task than the control animals on the second and third trial days.
      Further training eliminated this difference between the groups. Hippocampal mRNA
      expression of the NMDA subunits NR1, NR2A and NR2B, insulin-like growth factor
      type 1 receptor (IGF-1R), and postsynaptic density protein-95 (PSD-95) was then
      measured in the animals by Northern blot analysis. The results suggest that there
      may be a relationship between the NMDA receptor subunit mRNA expression levels
      and learning ability, and that learning is improved by rhGH in Hx rats.
      Furthermore, a link between MWM performance and PSD-95 was also suggested by this
      study.

PMID- 16633807
TI  - Sleepiness is not the inverse of alertness: evidence from four sleep disorder
      patient groups.
AB  - The constructs "sleepiness" and "alertness" are often assumed to be reciprocal
      states of consciousness. This distinction is of increasing concern in relation to
      psychomotor performance tasks such as driving. We developed two separate
      subjective scales of alertness to complement existing sleepiness scales.
      Subjective sleepiness and alertness were compared in four groups of sleep
      disordered patients. In a 175-patient cohort [25 narcoleptics and 50 each with
      sleep apnea, insomnia and periodic leg movement disorder (PLMD)], the Epworth
      Sleepiness Scale (ESS) was used to measure sleepiness while the Toronto Hospital
      Alertness Test (THAT) and ZOGIM Alertness Scale (ZOGIM-A) were used to measure
      alertness. Significant differences existed for sleepiness scores, with
      narcoleptics scoring highest on the ESS, followed by sleep apnea, with similar
      ESS scores for insomnia and PLMD. By contrast, alertness scores on both the THAT
      and ZOGIM-A did not differ significantly between the four groups. Sleepiness
      scores show a correlation of close to nil to alertness scores for the combined
      sleep disorder patient cohort, with the exception of insomnia patients, where a
      modest but significant inverse relationship was noted between sleepiness and
      alertness. Subjective states of impaired alertness and excessive sleepiness are
      independent constructs in the evaluation of sleep-disordered patients. The
      specific primary sleep disorder diagnosis may play a relevant role in mitigating
      this interrelationship.

PMID- 16633808
TI  - Impact of hypoxia and hypercapnia on calcium oxalate toxicity in renal epithelial
      and interstitial cells.
AB  - Although there is an ongoing controversy about the primary site of calcium
      oxalate stone (CaOx) formation, there is some evidence for extratubular
      crystallization. However, the mechanisms leading to such interstitial
      calcifications are not clear. Anatomical studies have demonstrated a close
      association between the renal vasculature and renal tubules. It has been
      hypothesized that disorders of the vasculature may contribute to renal stone
      formation. The exceptional papillary environment with low oxygen and high carbon
      dioxide is of interest in this context and its impact on CaOx toxicity to renal
      cells has to be evaluated. LLC-PK1, Madin-Darby canine kidney (MDCK), human
      umbilical vein endothelial (HUVEC) and fibroblast cell lines were exposed to
      hypoxia (3% O2) alone, hypercapnia combined with hypoxia (3% O2, 18% CO2) or
      standard culture conditions (20% O2) for 72 h. Cell survival rates were
      determined microscopically after 4 h of incubation with CaOx at final
      concentrations of 1, 2 and 4 mM. DAPI staining and western blot were used to
      evaluate the induction of apoptosis. We confirmed that CaOx leads to
      concentration-dependent effects on the viability of the cell lines. HUVECs were
      most vulnerable to CaOx among the four cell lines. Incubation under hypoxia alone
      had no impact on CaOx toxicity to any of the cell lines in terms of survival.
      However, under combined hypoxic and hypercapnic conditions, all cell lines
      displayed a significant reduction of cell survival compared to room air
      incubation. Again, this effect was most pronounced for HUVECs. The induction of
      apoptosis could not be demonstrated in any experimental setting. Combined hypoxia
      and hypercapnia clearly aggravate CaOx toxicity to renal cell lines. As we could
      not demonstrate the induction of apoptosis, this effect may be a result of toxic
      necrosis. Especially the CaOx effect on interstitial cell lines might be of
      interest in the chronic ischemic papillary environment. An increased toxicity may
      lead to recurrent stone formation, and vice versa, diseases of the vasculature,
      like arteriosclerosis, may further promote stone formation by induction of local
      ischemia. This issue has to be clarified by further studies.

PMID- 16633809
TI  - Prevention of nephrolithiasis by Lactobacillus in stone-forming rats: a
      preliminary study.
AB  - Hyperoxaluria is a risk factor for renal stones. It appears to be sustained by
      increased dietary load or increased intestinal absorption. The aim of this study
      was to evaluate whether oral administration of lactobacilli could prevent
      urolithiasis in stone-forming rats. Oxalate-degrading activities of lactobacilli
      were evaluated by measuring the oxalate level in a culture medium after
      inoculation with lactobacilli. Only the strains of Lactobacillus having oxalate
      degrading activity were used. Sprague-Dawley rats were fed a powdered standard
      diet containing 3% sodium oxalate and/or received 100 mg/kg of celecoxib for the
      first 8 days by gavage, before or after the beginning of this experiment (groups
      with previous treatment or with co-treatment). Rats were sacrificed after 4 weeks
      and kidneys were harvested for the assay of crystal formation under a dissecting
      microscope. Twenty-four-hour urine collections were performed before kidney
      harvest. Only two strains, Lactobacillus casei HY2743 and L. casei HY7201 out of
      31 strains of Lactobacillus were able to degrade oxalate. In both groups of co
      treatment and previous treatment with L. casei HY2743 and L. casei HY7201, urine
      oxalate excretion decreased compared to the group without lactobacilli. The
      dissecting microscope examination of kidneys in the rats in two previous
      treatment groups and the co-treatment group with L. casei HY7201 showed less
      abundant crystals than control groups. Our results show that lactobacilli may be
      used as a potential therapeutic strategy in the prevention of urinary stones.

PMID- 16633810
TI  - Treatment of subtrochanteric fractures. A comparison of the Gamma nail and the
      dynamic hip screw: short-term outcome in 58 patients.
AB  - The aim of this non-randomised prospective study was to evaluate the short-term
      outcome of Gamma nail and dynamic hip screw (DHS) fixation in the treatment of
      subtrochanteric hip fractures due to low-energy trauma in the elderly. All of the
      1,624 femoral hip fractures in 1,511 patients of the Oulu Hospital, aged over 49
      years, were prospectively registered from 1991-1999 using special forms. Seventy
      three (4.5%) of the fractures were subtrochanteric. After exclusions, 58 patients
      constituted the final study group. Of these, 43 were treated with Gamma nails and
      15 with DHS. Background factors before the fracture, complications, reoperations
      and functional parameters at 4 months were recorded using standardised forms.
      Intraoperative and hospital data were collected from patient records. The
      Seinsheimer fracture types IIIA, IIC and V were the most common fracture patterns
      when the Seinsheimer classification system was used, and Fielding II and AO
      31A3.3, respectively, were the most common types in the Fielding and AO
      classification system. There were four (9%) intraoperative complications in the
      Gamma nail group as compared to none in the DHS group. On the other hand,
      postoperative complications were more common in the DHS group (27%) than in the
      Gamma nail group (7%). We recognised a correlation between certain fracture types
      and the likelihood of typical intra- or postoperative complications or
      difficulties with both devices: In Gamma nailing, difficulty in closed reduction
      as well as the rate of open reduction and the use of supplementary fixation were
      most frequent in the Seinsheimer IIC fractures. It is also noticeable that all of
      the postoperative device failures and fracture displacements of the DHS group
      occurred in the Seinsheimer type IIIA category. Detailed fracture classification
      is essential for the choice of the fixation device, and the present study
      confirms the presumption that, despite the perioperative problems associated with
      Gamma nailing, this technique may be preferable to plate fixation for specific
      fracture types with medial cortical comminution, such as Seinsheimer type IIIA.

PMID- 16633811
TI  - Reliability of clinical diagnosis in meniscal tears.
AB  - This retrospective study was conducted to analyse the reliability of clinical
      diagnosis in meniscal tear injuries. All patients attending our clinic with knee
      pain from January 2003 to December 2004 underwent systematic and thorough
      clinical assessment. One hundred and fifty patients were clinically diagnosed to
      have meniscal tears. All these patients underwent therapeutic arthroscopic knee
      surgery. The clinical diagnosis was confirmed during this procedure. The
      accuracy, sensitivity and specificity were calculated based on these arthroscopic
      findings. The accuracy of clinical diagnosis in our study was 88% for medial
      meniscal tears and 92% for lateral meniscal tears. The results of this study
      demonstrate that clinical diagnosis of meniscal tears is as reliable as the
      results published by other authors for magnetic resonance imaging (MRI) scan. We
      recommend the use of MRI for more doubtful, difficult and complex knee injuries.

PMID- 16633812
TI  - Best practice in forensic entomology--standards and guidelines.
AB  - Forensic entomology, the use of insects and other arthropods in forensic
      investigations, is becoming increasingly more important in such investigations.
      To ensure its optimal use by a diverse group of professionals including
      pathologists, entomologists and police officers, a common frame of guidelines and
      standards is essential. Therefore, the European Association for Forensic
      Entomology has developed a protocol document for best practice in forensic
      entomology, which includes an overview of equipment used for collection of
      entomological evidence and a detailed description of the methods applied.
      Together with the definitions of key terms and a short introduction to the most
      important methods for the estimation of the minimum postmortem interval, the
      present paper aims to encourage a high level of competency in the field of
      forensic entomology.

PMID- 16633813
TI  - Effects of a brief worksite stress management program on coping skills,
      psychological distress and physical complaints: a controlled trial.
AB  - OBJECTIVES: To examine the effects of single-session, small-group stress
      management program on knowledge about stress, coping skills, and psychological
      and physical distress. METHODS: A total of 300 employees from a company in
      western Japan were invited to participate in the study. Those who consented to
      enter the study were assigned to an intervention (n=149) or waiting list control
      group (n=151). Participants in the intervention group received a small-group
      stress management program. The program was primarily aimed at increasing
      knowledge about stress and improving coping skills. To investigate the
      intervention effect, change scores in outcome variables were calculated by
      subtracting the scores at pre-intervention from those at post-intervention (8
      weeks after the pre-intervention survey). Next, the difference in the scores
      between groups was examined using analyses of covariance (ANCOVA) with the pre
      intervention score as the covariate. RESULTS: Favorable intervention effects were
      found on knowledge about stress and on coping skills (P<0.001 and P=0.012,
      respectively) and adverse effects on psychological distress (P=0.022). However,
      this adverse effect on psychological distress did not exist among those who
      initially perceived higher levels of job control. CONCLUSION: The single-session
      stress management program was effective on improving knowledge about stress, and
      coping skills, where job control moderated the effect of the program on
      psychological distress.

PMID- 16633814
TI  - ABA-responsive RNA-binding proteins are involved in chloroplast and stromule
      function in Arabidopsis seedlings.
AB  - The phytohormone abscisic acid (ABA) regulates essential growth and developmental
      processes in plants. Recently, RNA-binding proteins have been described as
      components of ABA signaling during germination. We have identified ten ABA
      regulated RNA-binding proteins in Arabidopsis seedlings. Among those genes,
      AtCSP41B and cpRNP29 are highly expressed in seedlings. Using promoter:reporter
      gene analyses, we showed that both AtCSP41B and cpRNP29 were in particular
      expressed in photosynthetically active organs like green cotyledons, leaves, and
      petioles. The analysis of CFP-fusion proteins demonstrates that cpRNP29 localized
      to chloroplasts and AtCSP41B to chloroplasts and stromules. Whereas RNA-binding
      of cpRNP29 has previously been shown, we demonstrated through in vitro RNA
      binding assays that recombinant AtCSP41B binds to RNA, and that chloroplast petD
      RNA can serve as a target of AtCSP41B. Developmental or environmental stimuli
      affected the expression of AtCSP41B and cpRNP29 in seedlings. Both genes were
      repressed during senescence, but only AtCSP41B was significantly repressed upon
      water stress. In addition, AtCSP41B and cpRNP29 exhibited low expression in
      etiolated seedlings compared to green seedlings, and cpRNP29 was regulated during
      the day photoperiod. Homozygous T-DNA insertion lines were isolated,
      characterized on the molecular level, and monitored for phenotypic changes. Taken
      together, the data show that both proteins are regulated during processes that
      are known to involve ABA signaling. Their localization in chloroplasts and RNA
      binding activity suggest a role in chloroplast RNA metabolism in Arabidopsis
      seedlings.

PMID- 16633818
TI  - The adrenal gland of newt Triturus carnifex (Amphibia, Urodela) following in vivo
      betamethasone administration.
AB  - The response of the adrenal gland of Triturus carnifex to betamethasone
      administration was studied; the effects were evaluated by examination of the
      ultrastructural morphological features of the tissues as well as the serum levels
      of aldosterone, corticosterone, norepinephrine and epinephrine. In March and
      June, betamethasone significantly decreased the serum levels of aldosterone and
      corticosterone and the lipid droplet content in the steroidogenic cells.
      Moreover, betamethasone influenced the chromaffin tissue, enhancing in March
      (when the chromaffin cells produce norepinephrine and epinephrine in almost equal
      quantities) epinephrine serum levels and the numeric ratio between norepinephrine
      and epinephrine granules in the chromaffin cells. In June, (when the chromaffin
      cells contain almost exclusively norepinephrine granules) betamethasone
      administration raised norepinephrine serum levels, whereas a decrease in the
      numeric ratio between norepinephrine and epinephrine granules in the chromaffin
      cells was found. Finally, betamethasone administration did not evoke in June any
      increase in the mean number of epinephrine granules in the chromaffin cells
      and/or in epinephrine serum levels, as would be expected if phenyletanolamine-N
      methyl transferase (PNMT) enzyme, converting norepinephrine into epinephrine,
      were activated by corticosteroids. The results of this study showed that
      betamethasone decreased aldosterone and corticosterone serum levels and enhanced
      catecholamine serum concentrations. Moreover, the present results suggest that a
      stimulatory role of glucocorticoids on PNMT enzyme may be ruled out.

PMID- 16633819
TI  - The urethral striated sphincter in adult male rat.
AB  - This study reports the morphology of the urethral sphincter in adult male rats,
      mainly the histological aspects, the features of the endplates, and the heavy
      myosin chain distribution in the striated fibres. First, the prostate is entirely
      out of the striated sphincter, which is surprising when compared to man. Second,
      the urethral striated sphincter consists of two lateral fascicles separated by an
      anterior and a posterior strip of connective tissue, which extend from the
      prostatic urethra (i.e. the part of the urethra which runs though the prostate)
      to the bulb of the penis. An additional third fascicle of striated muscle (SM)
      covers the caudal part of the anterior connective strip of the membranous urethra
      (i.e. the urethra which extends from its prostatic part to the bulb of the
      penis). In the membranous urethra, the striated sphincter surrounds directly the
      urethral lumen without intercalated smooth muscle. In urethral cross sections,
      the endplates detected by alpha-bungarotoxin, which binds to nicotinic receptors,
      are clustered in the postero-lateral part of the lateral fascicles. The cross
      sectional area of the urethral striated fibres shows a bimodal distribution: the
      largest fibres are located at the periphery of the sphincter and these fibres
      express only fast myosin heavy chains (MHC) as shown by immunochemistry. The
      smallest fibres are less numerous and are situated near the lumen co-expressing
      fast and slow MHC. All the striated fibres express desmin and dystrophin as SM
      fibres do. Taken together, these results suggest that the urethral striated
      fibres in male rat present the same characteristics as those of the skeletal
      muscles. The predominance of fast fibres is consistent with phasic contractions
      playing a role not only during micturition and urinary continence but also
      probably during ejaculation.

PMID- 16633820
TI  - Microvascular adaptation to growth in rat humeral head.
AB  - The aim of this work is to investigate the growth of the vasculature in the rat
      humeral head cartilage after the initial development of the secondary
      ossification centre until the adult organization. Rats aging from 5 weeks to 12
      months were used. Histological observations on humeral heads were implemented
      with morphometrical analysis. Subsequently, vascular corrosion cast, that permits
      a three-dimensional observation of the vasculature, were prepared and observed by
      scanning electron microscopy. In young animals the epiphysis contains thin bone
      trabeculae and most of the epiphysis is occupied by bone marrow spaces. With age,
      the bone trabeculae progressively enlarge up to double their thickness. The
      percentage of bone tissue increases from 33.6 to 58.6% of the entire epiphysis,
      while the bone marrow spaces tend to increase very little in their mean
      dimension. Vascular corrosion casts show that the epiphyseal microcirculation is
      well distinguished from that of the diaphysis, and arises from the vessels
      present in the capsule and the periosteal networks. In young animals the only
      capillaries are bone marrow sinusoids and few subchondral capillaries. In adult
      animals small vessels run between the clusters of sinusoids forming the
      trabecular circulation. Capillary sprouts from sinusoids are always observed both
      in the young and adult animals. Thus, in adult rats different proper
      microcirculatory districts can be distinguished in the epiphysis: (a) the
      sinusoidal network, that supplies the hematopoiesis of the bone marrow and the
      adjacent osteogenic tissue; (b) the bone tissue microcirculation, limited to
      small vessels that supply the metabolism and the remodelling of the bone tissue.
      The reported microvascular organization and its adaptation to the epiphyseal
      growth represent the morphological basis for understanding the reciprocal
      interaction among the different tissues in developing and adult rat epiphysis.

PMID- 16633821
TI  - Early development of chick embryo respiratory nervous system: an
      immunohistochemical study.
AB  - The extrinsic and intrinsic respiratory nervous systems receive specific
      contributions from the vagal and sympathetic components. Using specific markers
      for vagal and sympathetic structures, we studied the distribution patterns of
      immunoreactivity to galanin (GAL), pituitary adenylate cyclase-activating
      polypeptide-27 (PACAP) and the tachykinin substance P in extrinsic and intrinsic
      nerve of chick embryo respiratory system, during development from the very early
      age to hatching. All peptides studied appeared in the intrinsic and extrinsic
      nervous systems early. We found substance P in both the vagal and sympathetic
      systems, PACAP in vagal components alone and GAL mainly in the sympathetic
      system. The intrinsic nervous system showed high immunoreactivity for all
      peptides studied. These data accord with the well known early trophic functions
      that peptides have on the development of nervous networks and modulatory activity
      on the intrinsic nervous system. The GAL again proves to be the main peptide in
      chick embryo sympathetic respiratory system.

PMID- 16633822
TI  - Localized persistent interstitial pulmonary emphysema presenting as a spontaneous
      tension pneumothorax in a full term infant.
AB  - Persistent interstitial pulmonary emphysema (PIPE) is a syndrome characterized by
      air-leakage in the perivascular tissues of the lung, primarily affecting
      mechanically ventilated neonates. Reports in the literature of infants developing
      PIPE with no history of respiratory distress syndrome (RDS) or mechanical
      ventilation are scarce. Here, we present a case of a 3-month-old former full term
      male infant with no history of RDS or mechanical ventilation who presented with
      focal cystic lung disease associated with spontaneous tension pneumothorax. He
      was ultimately found to have PIPE based on pathologic evaluation of the resected
      cystic region. We believe that focal PIPE should be included in the differential
      diagnosis of cystic lung disease in a full term, unventilated infant, even when
      spontaneous pneumothorax is the presenting entity.

PMID- 16633824
TI  - Non-intubation traumatic laryngotracheal stenosis: management policies and
      results.
AB  - Traumatic laryngotracheal stenosis (LTS) is increasing in clinical practice.
      Causes include external trauma, post-intubation, and iatrogenic injuries. It is a
      complex problem and many patients undergo multiple procedures to achieve a stable
      and well-protected airway with adequate voice. We present our experience at Ain
      Shams University Hospitals on 15 patients followed-up for 7 years. All patients
      had traumatic LTS excluding post-intubation injuries. Patients were aged 4-58
      years. Nine were the victims of road traffic accidents; five were occupational
      trauma victims; and one tried to commit suicide by strangulation. The patients
      underwent a total of 53 procedures (mean 3.5 per patient). A total of seven
      laryngotracheal reconstruction, six partial cricotracheal resection, and four
      laser recanalization with stenting were performed. Six patients have mean follow
      up of 26.5 months (3-60 months). Six patients had normal speech (GRBAS 0-5),
      three had a moderate degree of voice disturbance (GRBAS 5-10), and five had
      severe dysphonia (GRBAS > 10). As regards tolerance for daily activities, we used
      a modification of the McMaster University asthma quality of life questionnaire
      [Rea et al. Eur J Cardiothorac Surg 22(3):352, 2002] (using the activities and
      emotional scores total 112). Four patients could perform above the 90th
      percentile; all the remaining patients were above the 50th percentile. No patient
      was totally handicapped as a result of their airway problem and they could tend
      for their basic activities. The aim of this work is to demonstrate that non
      intubation traumatic LTS is a complex problem that usually needs a longer time
      for reconstruction and a different way of approach. However, most of the patients
      can be finally rehabilitated with a stable, protected airway and adequate voice
      albeit at the price of a prolonged series of interventions and a long follow-up.

PMID- 16633825
TI  - Value of hyperbaric oxygen in bacterial and fungal malignant external otitis
      treatment.
AB  - Malignant external otitis (MEO) is an invasive, morbidity, even mortality, mainly
      pseudomonal infection of the external auditory canal, frequently involving the
      base of the skull, multiple cranial nerve and the meninges. In many cases
      conventional therapy has been prolonged, intensive and relatively ineffective,
      especially in infections other than bacterial (mainly fungal). We presented
      theoretical principles of hyperbaric oxygen (HBO) treatment in MEO, our own
      experience and others' experience in applying this treatment method. We treated
      eight patients with MEO applying pharmacotherapy, topical management, surgery in
      one case and also adjunct HBO. In six patients, infection was caused by
      Pseudomonas aeruginosa, in one by Staphylococcus sp. and in one by Aspergillus
      sp. Complete recovery was achieved in seven patients. In the patient with MEO
      caused by Aspergillus sp., intracranial complications developed and the patient
      died. Our experiences in employing HBO in bacterial-caused MEO have confirmed the
      role of HBO as a valuable, beneficial, supporting classical treatment method.
      Small number of patients with MEO, especially with non-bacterial infection, and
      unforeseen clinical course of disease make our experience difficult to
      objectivize.

PMID- 16633826
TI  - Cardiovascular responses to static extension and flexion of arms and legs.
AB  - This study compared cardiovascular responses to static extension and flexion
      exercises at four upper and lower limb joints. Eight males performed a 2 min
      static contraction at 30% of maximal voluntary torque followed immediately by 2
      min post-exercise muscle ischaemia (PEMI) using each of four joints: the wrist,
      elbow, ankle, and knee. In the PEMI, an occlusion cuff placed around the proximal
      portion of the exercising muscle was inflated to 250 mmHg immediately before the
      cessation of exercise. Mean arterial pressure (MAP), heart rate (HR), calf blood
      flow, and calf vascular conductance (CVC) in the non-exercised calf were
      measured. There was a significant interaction for direction of movement
      (extension vs. flexion) and limb (upper vs. lower) in HR and CVC during both
      exercise and PEMI; extension in the wrist and elbow evoked a greater increase in
      HR and a greater decrease in CVC than flexion, whereas flexion in the ankle and
      knee elicited a greater increase in HR and a greater decrease in CVC than
      extension. These results suggest that the cardiovascular responses to extension
      and flexion differ between arms and legs, partly arising from the activation of
      the muscle metaboreflex.

PMID- 16633828
TI  - A common missense variant in the LRRK2 gene, Gly2385Arg, associated with
      Parkinson's disease risk in Taiwan.
AB  - Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease
      (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic
      forms of PD remains largely unknown. Data are particularly limited concerning the
      Asian population. In search for novel, biologically relevant variants, we
      sequenced the LRRK2 coding region in Taiwanese patients with PD. Four newly
      identified variants and another variant recently found in a Taiwanese PD family
      were tested for association with the disease in a sample of 608 PD cases and 373
      ethnically matched controls. Heterozygosity for the Gly2385Arg variant was
      significantly more frequent among PD patients than controls (nominal p
      value=0.004, corrected for multiple comparisons=0.012, gender- and age-adjusted
      odds ratio=2.24, 95% C.I.: 1.29-3.88); this variant was uniformly distributed
      across genders and age strata. Two novel variants, Met1869Val and Glu1874Stop,
      were found in one PD case each; their pathogenic role remains, therefore,
      uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were
      present with similar frequency in cases and controls, and were therefore,
      interpreted as disease-unrelated polymorphisms. Our findings suggest that the
      LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which
      acts as common risk factor for sporadic PD in the population of Chinese
      ethnicity.

PMID- 16633830
TI  - Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin
      with or without systemic gemcitabine after curative resection for pancreatic
      adenocarcinoma.
AB  - BACKGROUND: The role of adjuvant therapy in pancreatic cancer remains
      controversial. Gemcitabine given systemically seems to be effective; intra
      arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS: The goal
      was to evaluate the impact of postoperative IAC followed or not by systemic
      gemcitabine in patients after curative resection for pancreatic adenocarcinoma. 5
      fluoruracil 750 mg sq m(-1), leucovorin 75 mg sq m(-1), epirubicin 45 mg sq m(
      1), carboplatin 225 mg sq m(-1) were administered every 3 weeks into celiac axis
      for three cycles (FLEC regimen), then gemcitabine at the dosage of 1 g sq m(-1)
      on days 1, 8 and 15 every 4 weeks for 3 months (FLECG regimen). RESULTS: Forty
      seven patients entered the study. The first 24 received only IAC (FLEC regimen),
      the other 23 received the same intra-arterial regimen followed by systemic
      gemcitabine (FLECG regimen). After a median follow-up of 16.9 months, 29 patients
      recurred (61.7%). Median disease free survival (DFS) was 18 months and median
      overall survival (OS) was 29.7 months. One-year DFS was 59.4% and 1-year OS was
      75.5%. Main grade 3 toxicity related to IAC was only nausea/vomiting in 4%;
      regarding gemcitabine, grade 3 toxicities were anaemia 8%, leukopenia 8%,
      thrombocitopenia 17%, nausea/vomiting 4%. CONCLUSIONS: FLEC regimen with or
      without gemcitabine is active with a very mild toxicity and results are very
      encouraging in an adjuvant setting.

PMID- 16633831
TI  - Systemic cytokine response in humans with chiclero's ulcers.
AB  - In this work, we report the existence of enhanced concentrations of IL-2 (Th1
      cytokine), TNF-alpha (mainly a Th1 cytokine), IL-12p40, a strong delayed type
      hypersensitivity response, and the absence of a serum-specific antibody response
      (IgG or IgE) in patients with active chiclero's ulcers. There was a low serum
      concentration of IL-6 (a Th2 cytokine) that was further reduced once patients
      healed following antimonial therapy (i.e., 4 months after treatment started).
      There was an absence of serum IL-4 (a Th2 cytokine) in patients before and after
      healing. The serum content of nitric oxide, transforming growth factor-beta1, and
      IL-12p70 in patients with progressive chiclero's ulcers was not different from
      that of controls. Patients had an alteration in blood-cell counts and showed a
      poor T cell proliferation after in vitro stimulation with Leishmania mexicana
      gp63. We concluded that patients with progressive chiclero's ulcers develop a Th1
      type of response at this stage of the disease which correlates with increases in
      circulating eosinophils and B cells and a reduction of circulating CD8(+) T
      lymphocytes.

PMID- 16633832
TI  - Human schistosomiasis haematobium: effective diagnosis of active infection using
      a pair of monoclonal antibodies against soluble egg antigen.
AB  - The present study was designed to prepare monoclonal antibodies (MAbs) against
      Schistosoma haematobium soluble egg antigen (SEA) with immunodiagnostic potential
      for urinary schistosomiasis. From a panel of MAbs, a pair of IgG1 MAbs (2D/11C
      and 10B/2C) specific for S. haematobium SEA was selected. Both MAbs recognized
      one band with a 42-kDa molecular weight by western blots. The pair of MAbs was
      employed in sandwich ELISA for the detection of circulating schistosome antigen
      (CSA), one as antigen-capturing antibody and the other as peroxidase-conjugated
      antigen-detecting antibody. The lower detection limit of the assay was 1 ng/ml of
      S. haematobium SEA. The assay was performed on sera of 65 S. haematobium-infected
      patients, 25 patients infected with other parasites (Fasciola hepatica,
      Echinococcus granulosus), and 20 noninfected individuals. CSA was demonstrated in
      89% of the S. haematobium-infected group. However, CSA was negative in the sera
      of healthy individuals and patients infected with other parasites, giving an
      overall specificity of 100% for the CSA assay. A positive correlation (r=0.37,
      p<0.01) was detected between the number of S. haematobium eggs excreted in 10 ml
      urine and the CSA level detected in the sera of S. haematobium-infected patients.
      Our data show that the use of anti-S. haematobium MAbs for the detection of CSA
      provides a sensitive and specific method for the immunodiagnosis of active S.
      haematobium-infected patients. Moreover, CSA assay using this anti-S. haematobium
      MAb/ELISA system was proven to correlate with intensity of infection and hence
      morbidity assessment.

PMID- 16633840
TI  - Communication and informed consent in phase 1 trials: a review of the literature.
AB  - Phase 1 (P1) trials are vital to the development of cancer treatments; however,
      the patients involved in these trials are unlikely to receive any therapeutic
      benefit, and there are significant possibilities that they will experience
      serious side effects. Ethical requirements stipulate that patients must be
      adequately informed before they consent to participate in P1 trials. This review
      focuses on studies that have measured patient comprehension of information given
      during the informed consent process of P1 cancer trials. Patients consenting to
      participate in P1 trials currently have a limited understanding of trial purpose,
      an unrealistic expectation of the benefits and risks associated with trial
      participation and a questionable appreciation of their right to abstain or
      withdraw. Health care professionals recruiting to P1 trials need clear and
      practical guidelines and training packages designed to ensure that all details of
      P1 trials are communicated effectively to eligible patients.

PMID- 16633841
TI  - Altered food intake and taste perception in children with cancer after start of
      chemotherapy: perspectives of children, parents and nurses.
AB  - GOALS OF WORK: The purpose of this study was to better understand various
      variables related to food intake and eating problems in children with cancer
      during their chemotherapy. PATIENTS AND METHODS: Twenty-two consecutively
      admitted children, diagnosed with cancer and undergoing chemotherapy,
      participated in this study. Twenty-one of them, their parents and attending
      nurses participated in semi-structured interviews. Ten of the children underwent
      a taste acuity test, and recognition thresholds for the four basic tastes were
      determined. MAIN RESULTS: The shared view of both children and parents was that
      altered taste was the predominant cause of the eating problems. In contrast, the
      nurses perceived that nausea was the most important cause of the children's
      eating problems. In addition, psychological aspects such as learned food
      aversions and negative attitudes towards hospital food were regarded as important
      by children, parents and nurses. The taste test showed that the patients had
      higher thresholds for bitter taste and made more taste recognition errors
      compared to controls. CONCLUSIONS: Changes seem to exist both in the primary
      gustatory sense as well as in food perception in paediatric cancer patients
      undergoing chemotherapy. Single solutions, such as efforts to serve "tasty food",
      do not suffice alone. A more effective solution may be to combine different
      strategies and combinations of oral, enteral and parenteral nutrition should be
      considered to prevent malnutrition.

PMID- 16633842
TI  - External nasal dilator strips (ENDS) may improve breathlessness in cancer
      patients.
AB  - RATIONALE: ENDS (external nasal dilator strips) are adhesive bands containing a
      central elastic strip providing a spring action. The possibility of reducing the
      cumulated effort of continuous breathing or decreasing the perception of exertion
      would be of major benefit to oncological dyspneic patients, namely in presence of
      a cachexia-asthenia complex. METHODS: Nine patients complaining of dyspnea were
      included in this pilot study. The ENDS were applied at 0800 and at 1600.
      Perception of dyspnea and tolerability was assessed 12 h after the first
      application of the ENDS. No other treatment changes were performed during the
      evaluation time. RESULTS: As a result of the application of ENDS, one patient
      perceived a good improvement of dyspnea, three moderate, two little, and three
      none. Tolerability was good for four patients and moderate for another four.
      Seven out of nine patients decided to carry on with the application of ENDS
      afterwards. CONCLUSIONS: The application of ENDS may be useful in cancer patients
      with dyspnea. It could be particularly helpful to patients suffering from
      cachexia and profound fatigue. However, further research is needed to affirm that
      ENDS might have an important place in relieving dyspnea.

PMID- 16633843
TI  - Brief oral cryotherapy for the prevention of high-dose melphalan-induced
      stomatitis in allogeneic hematopoietic stem cell transplant recipients.
AB  - We previously reported the efficacy of oral cryotherapy for the prevention of
      high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate
      whether the further shortening of the duration of oral cryotherapy could minimize
      its side effects while sparing its efficacy. Seventeen consecutive recipients of
      allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan
      in combination with fludarabine alone or with fludarabine and additional
      radiation were enrolled in the study. The severity of stomatitis was graded
      according to the National Cancer Institute-Common Toxicity Criteria. Patients
      were kept on oral cryotherapy shortly before, during, and for additional 30 min
      after the completion of melphalan administration (60-min oral cryotherapy).
      Patients who were also enrolled in our previous study received the same type of
      oral cryotherapy but for additional 90 min after the completion of melphalan
      administration (120-min oral cryotherapy), and they served as controls. Only 2
      (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18
      patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis,
      respectively. The difference between groups was not statistically significant (P
      = 0.677). The incidence of unpleasant symptoms such as chills and nausea during
      oral cryotherapy decreased significantly with 60-min oral cryotherapy, as
      compared with that associated with 120-min oral cryotherapy (P < 0.01). These
      results suggest that 60-min oral cryotherapy is as effective as 120-min oral
      cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter
      treatment might have contributed to relieve patient discomfort during oral
      cryotherapy.

PMID- 16633845
TI  - Evidence for an association between type 1 diabetes and premature carotid
      atherosclerosis in childhood.
AB  - Acute phase proteins have been suggested to be increased in patients with type 1
      diabetes. The aim of this study was to evaluate the relationship between serum C
      reactive protein (CRP) and intima-media thickness (IMT) and functions of the
      common carotid artery (CCA) in children and adolescents with type 1 diabetes.
      Serum CRP levels were measured in 65 children and adolescents with diabetes (33
      girls and 32 boys; mean age, 12.7 +/- 3.8 years; range, 7-18; duration of
      diabetes, 6.9 +/- 3.6 years). Age and diabetes duration, as well as major
      cardiovascular risk factors including anthropometric and metabolic parameters,
      were matched between girls and boys. The relations of serum CRP levels to CCA
      structure and functions were measured by ultrasonography as IMT, cross-sectional
      compliance, cross-sectional distensibility, diastolic wall stress (DWS), and
      incremental elastic modulus (IEM). There was no significant difference for serum
      CRP levels between girls and boys (3.7 +/- 1.3 vs 3.2 +/- 0.4 mg/L; p > 0.05).
      CRP was positively correlated with IMT (r = 0.49, p = 0.001), IEM (r = 0.24, p =
      0.05), DWS (r = 0.58, p < 0.001), and body mass index (BMI) (r = 0.28, p = 0.05).
      In a multivariate regression model, we included CRP and metabolic and
      anthropometric parameters such as duration of diabetes, HbA1c, BMI, waist:hip
      ratio, age, and systolic and diastolic blood pressure as independent variables in
      the model for CCA structure and functions. CRP emerged as an independent
      correlation for mean IMT (beta = 0.51, p < 0.001) and DWS (beta = 0.61, p <
      0.001). According to our findings, CRP was associated with CCA structure and
      functions in children and adolescents with type 1 diabetes.

PMID- 16633859
TI  - Strategies for optimizing treatment with efalizumab in moderate to severe
      psoriasis.
AB  - With the advent of biological therapies for the treatment of plaque psoriasis,
      guidance on the usage of these new agents has become necessary. One such agent,
      efalizumab, a humanized recombinant monoclonal IgG(1) antibody developed to
      target T-cell-mediated inflammation, provides rapid and sustained efficacy for
      many psoriasis patients. This article explores the pretreatment, initiation, and
      treatment phases with efalizumab therapy. In the pretreatment phase, physicians
      need to assess patients' disease state and educate them about the course of
      efalizumab treatment. Prior to initiation, physicians need to establish stable
      disease, ensure an adequate transition or washout of any prior psoriasis
      therapeutics, and obtain baseline platelet counts. After initiating treatment,
      both physician and patient must participate in disease monitoring. Patients
      responding favourably may receive continuous treatment. Those who do not respond
      to the drug or who experience adverse events should be managed appropriately in
      order to continue therapy or be transitioned onto another agent. A growing body
      of clinical evidence, as well as experience from clinical investigators, has
      provided much insight into the management strategies for patients undergoing
      treatment with efalizumab.

PMID- 16633860
TI  - Recommendations for incorporating biologicals into management of moderate to
      severe plaque psoriasis: individualized patient approaches.
AB  - Psoriasis is a T-cell mediated skin disease that affects approximately 2% of the
      population worldwide. Despite the prevalence of the disease and long-standing
      efforts to develop strategies to treat it, there is a need for safe and effective
      therapies to treat psoriasis, particularly the more severe forms. Biological
      agents such as alefacept, efalizumab, etanercept, and infliximab have been
      recognized as a class of treatment distinct from other forms of therapy in the
      treatment algorithm of psoriasis. Recent national and international consensus
      meetings have developed statements that position biological agents as an
      important addition to the treatment armamentarium for moderate to severe
      psoriasis, along with phototherapy and traditional systemic agents. There has
      been consensus that treatment should be individualized to each patient's needs
      and circumstances. Biological agents offer the hope of safe, effective, long-term
      management of moderate to severe psoriasis. As new agents receive approval from
      Health Canada, the available range of therapeutic options for treating this
      chronic disease will broaden. A Canadian Psoriasis Expert Panel recently convened
      in February 2005 to analyze, based on a series of clinical case scenarios, the
      indications, contraindications, and considerations for and against each of the
      four biological agents, derived from product labelling, where available, and from
      the efficacy and safety data from phase 3 and earlier clinical trials, as well as
      post-marketing reports. The Panel has formulated a set of recommendations for
      incorporating these biological agents into the current treatment paradigm of
      moderate to severe plaque psoriasis and has identified the preferred biological
      agents for each patient based on individual needs and circumstances.

PMID- 16633861
TI  - A favourable benefit/risk ratio with efalizumab: a review of the clinical
      evidence.
AB  - Moderate to severe plaque psoriasis has traditionally been treated with agents
      that have toxicities associated with long-term use. Many patients therefore
      cannot be treated safely, conveniently or effectively with traditional therapies.
      Recent phase 3 clinical trials for efalizumab, a biological agent targeted
      specifically at the T-cell-based pathology of psoriasis, have demonstrated its
      short- and long-term efficacy and safety for the treatment of psoriasis. This
      article reviews results from 12-week, six-month, and three-year trials, focusing
      on the drug's safety, efficacy, and therapeutic response time, as well as the
      phenomenon of rebound in non-responding patients. Efalizumab emerges as an
      important addition to the dermatological pharmacopeia for the long-term treatment
      of psoriasis.

PMID- 16633862
TI  - Efalizumab, a reversible T-cell modulator for psoriasis.
AB  - The humanized monoclonal antibody (MAb) efalizumab (Raptiva) was developed to
      meet a longstanding need for specific, safe, and effective anti-psoriatic
      treatments. Efalizumab, which is directed at the lymphocyte surface protein LFA
      1, prevents multiple interactions between T cells and other cell types. Here, we
      review the inflammatory pathway that drives the development of psoriasis, and we
      discuss several mechanisms by which efalizumab suppresses skin inflammation in
      psoriasis. Efalizumab reversibly increases circulating T-cell counts, as T cells-
      including pathogenic CD8 memory T cells that are prominent in psoriatic lesions--
      are specifically restrained from leaving the bloodstream and entering the skin.
      Within two weeks of the onset of efalizumab treatment, cell surface and
      intracellular LFA-1 pools are substantially cleared by lysosomal degradation.
      Residual surface LFA-1 molecules remain saturated with bound efalizumab for some
      weeks following cessation of treatment. Efalizumab's pharmacodynamic properties
      are consistent with its profound and reversible beneficial effects on the
      histopathology of psoriatic skin.

PMID- 16633863
TI  - Efalizumab: integrating a new biologic agent into the long-term management of
      moderate to severe plaque psoriasis.
AB  - Efalizumab, one of a new generation of biological agents, has been approved for
      use in moderate to severe psoriasis in over 35 countries including Canada. It may
      hold the promise of a new level of safe, long-term disease control for psoriasis
      patients, who have had few adequate options to date. Dermatologists and other
      caregivers may require some background regarding the mechanisms of action and the
      optimal use of this drug before integrating it into their standard repertoire of
      treatment. The present supplement discusses efalizumab's biological basis and
      reviews its clinical safety and efficacy. The salient differences amongst the
      various biologicals, with regard to safety, efficacy and convenience, are also
      considered. The supplement concludes with a practical guide to initiating and
      maintaining patients on efalizumab treatment.

PMID- 16633867
TI  - The effects of intraoral pressure sensors on normal young and old swallowing
      patterns.
AB  - Lingual pressure generation plays a crucial role in oropharyngeal swallowing. To
      more discretely study the dynamic oropharyngeal system, a 3-bulb array of
      pressure sensors was designed with the Kay Elemetrics Corporation (Lincoln Park,
      NJ). The influence of the device upon normal swallowing mechanics and boluses
      representative of flow relative to age and bolus condition was the focus of this
      study. Twelve healthy adults in two age groups (31 +/- 5 years, 2 males and 4
      females, and 78 +/- 7 years, 2 males and 4 females) participated. Each subject
      was instructed to swallow four boluses representative of conditions with and
      without three pressure sensors affixed to the hard palate. Post-swallow residue
      at four locations, Penetration/Aspiration Scale scores, and three bolus flow
      timing measures were assessed videofluoroscopically with respect to age and bolus
      condition. The only statistically significant influences attributable to the
      presence of the pressure sensors were slight increases in residue in the oral
      cavity and upper esophageal sphincter with some bolus consistencies, 8% more
      frequent trace penetration of the laryngeal vestibule predominantly with
      effortful swallowing, and variances in oral clearance duration. We conclude that
      the presence of the pressure sensors does not significantly alter normal
      swallowing patterns of healthy individuals.

PMID- 16633868
TI  - Oropharyngeal stimulation with air-pulse trains increases swallowing frequency in
      healthy adults.
AB  - This study sought to determine whether air-pulse trains delivered to the
      peritonsillar area would facilitate swallowing in healthy subjects. Trains of
      unilateral or bilateral air pulses were delivered to the peritonsillar area via
      tubing embedded in a dental splint, while swallows were simultaneously identified
      from their associated laryngeal and respiratory movements. Results from four
      subjects indicated that oropharyngeal air-pulse stimulation evoked an
      irrepressible urge to swallow, followed by an overt swallow as verified by
      laryngeal and respiratory movements. Moreover, air-pulse stimulation was
      associated with a significant increase in swallowing frequency. Mean latency of
      swallowing following bilateral stimulation tended to be less than the latency of
      swallowing following unilateral stimulation. These findings in healthy adults
      suggest the possibility that oropharyngeal air-pulse stimulation may have
      clinical utility in dysphagic individuals.

PMID- 16633869
TI  - Comparison of esophageal motility in patients with solid dysphagia and mixed
      dysphagia.
AB  - It is unclear whether there is any difference in esophageal motor abnormalities
      between patients complaining of dysphagia for solids or both solids and liquids.
      The aim of this study was to determine any difference in the manometric findings
      between patients with dysphagia for solids and those with mixed dysphagia.
      Manometric tracings were performed in 200 consecutive patients (66 M, 134 F; mean
      age = 51 years) with nonobstructive dysphagia. Ambulatory pH studies were
      performed in all patients. Subjects were divided into two groups: patients with
      solid dysphagia (n = 94, 33 M, 61 F; mean age = 51 years) and those with mixed
      dysphagia (n = 106, 33 M, 73 F; mean age = 51 years). A normal motility study was
      the most frequent finding. Achalasia occurred more frequently in patients with
      mixed dysphagia than in those with solid dysphagia (12% vs. 3%, p < 0.01).
      Gastroesophageal reflux disease (GERD) was observed in 59% of patients with solid
      dysphagia compared with 29% of patients with mixed dysphagia (p < 0.02). The most
      common esophageal motility abnormality is nonspecific esophageal motility
      disorders. This study has shown that abnormal esophageal motility occurs slightly
      more in mixed dysphagia than solid dysphagia. The clinical utility of a
      symptomatic differentiation of patients with solid or mixed dysphagia appears to
      be limited.

PMID- 16633870
TI  - Bolus location at the initiation of the pharyngeal stage of swallowing in healthy
      older adults.
AB  - This study characterized the vertical position of the bolus head at the onset of
      the pharyngeal swallow in healthy older adults. Lateral-view videofluoroscopic
      (VF) images were obtained from ten healthy volunteers (age-71.6 +/- 7.5 years,
      mean+/- SD) as they swallowed 5-cc thin liquid barium aliquots. For each swallow,
      the bolus head and several anatomic landmarks were digitally recorded from the
      image in which pharyngeal swallow-related hyoid bone elevation began. Vertical
      distance between the bolus head and the intersection of the tongue base and
      mandibular ramus (TMI) was computed. Bolus head position at swallow onset ranged
      from 47.4-mm above to 34.9-mm below the TMI (2.2 +/- 14.4-mm, mean +/- SD).
      Although the bolus head was below the level of the TMI for the majority of
      swallows, neither penetration nor aspiration occurred. For individual subjects,
      mean bolus head position ranged from 25.8 +/- 5.0-mm above to 15.5 +/- 6.5-mm
      below the TMI. Whereas five of ten subjects initiated the pharyngeal swallow with
      the bolus head consistently above or consistently below the TMI, five subjects
      initiated swallowing with the bolus head either above or below the TMI across
      trials. Older adults commonly initiate thin-liquid swallows with the bolus head
      well below the TMI without associated penetration or aspiration. Thus, bolus
      position alone does not differentiate between normal and pathologic swallowing
      within the healthy elderly. Bolus position at pharyngeal swallow onset can vary
      substantially from trial to trial within an individual, suggesting that the
      triggering of swallowing depends on multiple influences.

PMID- 16633871
TI  - Swallow syncope in association with Schatzki ring and hypertensive esophageal
      peristalsis: report of three cases and review of the literature.
AB  - Syncope caused by swallowing-induced cardiac arrhythmia is an uncommon condition.
      The recognition of this syndrome is paramount but often difficult. We report
      three cases of deglutition syncope evaluated at our institution over a three-year
      period. Two patients had distal esophageal (Schatzki) ring and two had
      hypertensive peristaltic waves (commonly referred to as "nutcracker esophagus"),
      neither of which had been described before in association with deglutition
      syncope. Two patients underwent placement of a demand cardiac pacemaker with
      subsequent resolution of their syncopal symptoms, while the third patient refused
      any further intervention. Swallow syncope usually follows a benign course from a
      cardiac standpoint. Placement of a demand cardiac pacemaker can prevent
      recurrence of presyncopal and syncopal attacks and their untoward consequences.

PMID- 16633872
TI  - Sensitivity of upper endoscopy in diagnosing esophageal cancer.
AB  - Esophageal cancer is a common cause of dysphagia and upper endoscopy is the
      accepted standard for making the diagnosis; however, the accuracy of endoscopy is
      not known. The purpose of this study is to determine the sensitivity of upper
      endoscopy in making the diagnosis of esophageal cancer in clinical practice. All
      patients with a new diagnosis of esophageal cancer from 1997 to 2001 in the Tumor
      Registry of Wake Forest University Baptist Medical Center were identified. The
      medical records were reviewed to identify all patients who had undergone a
      previous endoscopy within two years that failed to diagnose esophageal cancer.
      The reason for failure was recorded. One hundred ten new cases of esophageal
      carcinoma were identified, and ten patients had had a previous false-negative
      endoscopy within two years for a sensitivity of 90.9% in clinical practice. The
      reasons for the failure of endoscopy were (1) lesion not seen in seven patients,
      (2) lesion seen and biopsied with benign histology in two patients, and (3)
      lesion seen but felt to be benign and not biopsied in one patient. Given the
      uncertain natural history of esophageal cancer, the data were also analyzed using
      a one-year window; this resulted in a sensitivity of 94.5%. The sensitivity of
      upper endoscopy in the diagnosis of esophageal cancer in general clinical
      practice is 90.9% using a two-year window and 94.5% using a one-year window.
      Understanding the reasons for the failure of endoscopy may allow us to improve
      the practice of endoscopy.

PMID- 16633873
TI  - Effects of the removal of the tracheotomy tube on swallowing during the
      fiberoptic endoscopic exam of the swallow (FEES).
AB  - This study investigated the effects, if any, that the presence of a tracheotomy
      tube has on the incidence of laryngeal penetration and aspiration in patients
      with a known or suspected dysphagia. This was a prospective, repeated-measure
      design study. A total of 37 consecutive patients with a tracheotomy tube
      underwent a fiberoptic endoscopic evaluation of swallowing (FEES). Patients were
      first provided with pureed food boluses with the tracheotomy tube in place. The
      tracheotomy tube was then removed and the tracheostoma site was covered with
      gauze and gentle hand pressure was applied. The patients were then evaluated
      without the tracheotomy tube in place with additional puree. Aspiration status
      was in agreement with and without the tracheotomy tube in place in 95% (35/37) of
      the patients. The two patients who demonstrated a different swallowing pattern
      with regard to aspiration demonstrated aspiration only when the tracheotomy tube
      was removed. Laryngeal penetration status was in agreement with and without the
      tracheotomy tube in place in 78% (29/37) of the patients. For the majority of the
      patients, the removal of the tracheotomy tube made no difference in the incidence
      of aspiration and/or laryngeal penetration. Results of this study do not support
      the clinical notion that the patient's swallowing function will improve once the
      tracheotomy tube has been removed.

PMID- 16633874
TI  - Temporal measurements of pharyngeal swallowing in normal populations.
AB  - The purpose of this investigation was to examine the temporal differences among
      three measures of pharyngeal stage transition in 40 normal subjects. The measures
      were (1) Pharyngeal Delay Time (PDT), (2) Stage Transition Duration (STD), and
      (3) Delayed Pharyngeal Swallow (DPS). Results showed a significant difference
      between younger and older subjects for PDT and STD but not for DPS. No gender
      differences were observed. These data on normal subjects will be used for
      comparisons with stroke patients in future research.

PMID- 16633875
TI  - Use of respiratory inductance plethysmography for the detection of swallowing in
      the elderly.
AB  - It is essential to have a user-friendly, noninvasive bedside procedure at our
      disposal in order to study swallowing and swallowing disorders in the elderly in
      view of the frailty of this age group. In the present work, respiratory
      inductance plethysmography (RIP) is proposed as an appropriate clinical tool for
      such studies. An automated process for the detection of swallowing is used
      involving the derivative of the respiratory volume signal. The accuracy of the
      automated detection is given by the area under the Receiver Operating
      Characteristic (ROC) curve and is found to be greater than 0.9. At the optimal
      threshold, RIP constitutes a reliable and objective bedside clinical tool for
      studying swallowing in the elderly, as well as being user-friendly and
      noninvasive. In addition, RIP can be used to monitor swallowing in order to
      analyze swallowing disorders and put in place medical supervision of swallowing
      for individuals who might aspirate.

PMID- 16633876
TI  - Predicting prolonged dysphagia in acute stroke: the Royal Adelaide Prognostic
      Index for Dysphagic Stroke (RAPIDS).
AB  - Dysphagia is common after stroke and is associated with increased morbidity and
      mortality. Predicting those who are likely to have significant prolonged
      dysphagia is not possible at present. This study was undertaken to validate the
      Royal Adelaide Prognostic Index for Dysphagic Stroke (RAPIDS) in the prediction
      of prolonged dysphagia following acute stroke using clinical and radiographic
      features. A prospective study of unselected, consecutive admissions to the Royal
      Adelaide Hospital acute stroke unit was undertaken. Clinical and radiographic
      features applicable to the RAPIDS test were calculated and the sensitivity,
      specificity, and likelihood ratio for predicting prolonged dysphagia were
      calculated with 95% confidence intervals (CI). Of 104 subjects admitted with
      acute stroke, 55 (53%) had dysphagia and 20 (19%) had dysphagia requiring nonoral
      feeding/hydration for 14 days or more or died while dysphagic prior to 14 days.
      The RAPIDS test had sensitivity of 90% (95% CI = 70-97%) and specificity of 92%
      (95% CI - 84-96%) for predicting this latter group of patients. We conclude that
      the RAPIDS test can be used early to identify patients likely to have prolonged
      dysphagia. This test could form a basis for selection of patients for trials of
      nonoral feeding methods.

PMID- 16633877
TI  - Effect of tactile stimulation on lingual motor function in pediatric lingual
      dysphagia.
AB  - There is a scarcity of empirical evidence on effective treatments of swallowing
      dysfunction in young children who do not suck or swallow. There is no literature
      testing the effects of shaping a reflex or specifically shaping a swallow reflex.
      The purpose of this retrospective study was to investigate and isolate the
      specific regional mechanical functions of the tongue during swallowing. This
      study included 45 patients who did not swallow because of multiple congenital
      anomalies and gastroenterologic dysfunctions before and after corrective surgery
      and had histories of unsuccessful traditional feeding therapies. Evaluation
      included clinical gastroenterologic, nutritional, and neurologic examination,
      routine laboratory tests, and radiologic swallowing studies. A ten-year study
      analyzed the behavioral science procedures shaping both a swallow reflex and
      lingual surface geometry. Treatment variables were (1) a tactile stimulus to the
      posterior tongue and (2) sequential tactile stimuli to varied locations on the
      lingual surface. There were significant differences in lingual responses for all
      patients who were transferred from artificial feedings to independent
      prototypical swallowing capability and acquired oral consumption of recommended
      daily hydration and nutrition in 5-7 days of treatment. The initial tactile
      stimulus and six-level sequential stimuli resulted in six sequential lingual
      responses within each wavelike swallow reflex. Results of stimuli shaping varied
      lingual responses across 45 patients with severe multiple medical and anatomical
      deficits in swallowing, suggest that the etiology was not relevant in this
      population. These behavioral science approaches are novel treatment for pediatric
      lingual dysphagia.

PMID- 16633878
TI  - Viscosity measurements of nectar- and honey-thick liquids: product, liquid, and
      time comparisons.
AB  - This study compared the viscosity (thickness) of five different liquids thickened
      to nectar- or honey-like consistencies with a variety of thickening products.
      Samples were prepared using manufacturer guidelines and viscosity was measured at
      the recommended time to thicken (standard) and also after 10 and 30 min.
      Centipoise (cP) measurements of the samples were compared across products and
      within product lines for each level of thickness at all three time periods.
      Statistical analysis showed that the viscosity of a nectar- or honey-like liquid
      was highly dependent on the type of thickening product and the time it was
      allowed to thicken. Variability in viscosity measurements also was noted within a
      product line for thickening various liquids. Results are discussed in relation to
      the National Dysphagia Diet guidelines for nectar- and honey-like consistencies.

PMID- 16633879
TI  - Searching for meaningful differences in viscosity.

PMID- 16633883
TI  - The prevalence of voiding difficulty after TVT, its impact on quality of life,
      and related risk factors.
AB  - OBJECTIVE: To determine the prevalence of voiding difficulty (VD), quality of
      life, and related risk factors after tension-free vaginal tape (TVT). DESIGN:
      Prospective cohort study in 703 women with a TVT procedure for stress urinary
      incontinence. MAIN OUTCOME MEASURES: VD stated by women, Urogenital Distress
      Inventory (UDI-6) question 5 (difficulty in emptying the bladder), maximum flow
      rate, postvoid residual urine, necessity of postoperative catheterization, tape
      division, and impact on quality of life (Incontinence Impact Questionnaire, IIQ
      7). RESULTS: Postoperative catheterization (>24 h) was necessary in 11% and tape
      division in 1.3% of patients. There were 26% of women who stated VD and 25%
      reported moderate to great impairment on the UDI-6 after 36 months. While the
      negative impact on the outcome of TVT in women with abnormal voiding compared to
      women without is higher, the impact decreased significantly after TVT, implying a
      considerable improvement in quality of life. Pre-operative existing voiding
      difficulty and concomitant prolapse surgery were independent risk factors.
      CONCLUSIONS: Symptoms of VD occurred after TVT and caused lesser improvement in
      quality of life.

PMID- 16633884
TI  - Nerve injury: an exceptional cause of pain after TVT.
AB  - Persistent pain after a tension-free vaginal tape procedure is rare. Perforation
      or erosion of the tape into the bladder, urethra, or vagina; hematoma formation;
      and tape rejection are the most common causes. Less frequent causes are injury to
      the pelvic bone or to iliopectineal ligaments. In this case report, we present
      the passage of the tape through a nerve structure as the source of persistent and
      severe retropubic pain. Diagnostic procedures, such as cystoscopy, ultrasound,
      and MRI scanning, showed no abnormal findings. Treatment was initially
      conservative, but only locally injected analgesics and corticosteroids relieved
      the pain temporarily. Finally, surgical exploration revealed the inadvertent
      course of the tape through branches of the ilioinguinal/iliohypogastric nerve,
      which only became clear after pathological examination of the excised tape.

PMID- 16633887
TI  - Screening for autistic spectrum disorder in children aged 14-15 months. II:
      population screening with the Early Screening of Autistic Traits Questionnaire
      (ESAT). Design and general findings.
AB  - A two-stage protocol for screening for autistic spectrum disorders (ASD) was
      evaluated in a random population of 31,724 children aged 14-15 months. Children
      were first pre-screened by physicians at well-baby clinics using a 4-item
      screening instrument. Infants that screened positive were then evaluated during a
      1.5-h home visit by a trained psychologist using a recently developed screening
      instrument, the 14-item Early Screening of Autistic Traits Questionnaire (ESAT).
      Children with 3 or more negative scores were considered to be at high-risk of
      developing ASD and were invited for further systematic psychiatric examination.
      Eighteen children with ASD were identified. The group of children with false
      positive results had related disorders, such as Language Disorder (N = 18) and
      Mental Retardation (N = 13).

PMID- 16633890
TI  - Pharmacokinetic/pharmacodynamic modeling of total lymphocytes and selected
      subtypes after oral budesonide.
AB  - In the present pharmacokinetic/pharmacodynamic (PK/PD) evaluation, cortisol,
      total lymphocytes, and lymphocyte subpopulations were monitored following single
      oral doses of two oral formulations of 3 mg budesonide (BUD) (Dosage Forms A and
      B) in order to assess the differential effects that BUD may have on cortisol
      suppression and the modulation of blood lymphocyte subtypes. On a single
      occasion, five subjects received one 3 mg capsule of Dosage Form A, four received
      three capsules of Dosage Form A (single dose of 9 mg), and five received three
      capsules of Dosage Form B (single dose of 9 mg). Placebo capsules were
      administered to six subjects in the study. Cortisol concentrations, total
      lymphocyte counts, and lymphocyte subpopulation counts for the CD3, CD4, CD8,
      CD19, and CD56/16 were fitted to an in direct PK/PD response model that described
      the effects of BUD on serum cortisol concentrations as well as the combined
      effects of BUD and cortisol on total lymphocytes and the CD3, CD4, CD8, CD19, and
      CD56/16 subtypes. Data were also analyzed using noncompartmental methods. The
      PK/PD model fitted the data with the exception of data for CD56/16. The IC(50)
      value for unbound BUD acting on total lymphocytes was 0.276 ng/ml while the
      IC(50) values for unbound BUD acting on lymphocyte subtypes ranged from 0.150
      ng/ml for CD4 to 0.364 ng/ml for CD8. The IC(50) values for the effects of BUD on
      serum cortisol were lower (0.079 ng/ml). The results of PK/PD modeling and
      noncompartmental analysis indicate that BUD has a smaller effect on the CD8
      subtype and larger effects on the CD4 and CD19 subtypes, relative to the effect
      on total lymphocytes, and that cortisol suppression, although not a direct
      immunological biomarker, may be a more sensitive marker for the systemic effect
      of corticosteroids.

PMID- 16633891
TI  - CREB and NF-kappaB transcription factors regulate sensitivity to excitotoxic and
      oxidative stress induced neuronal cell death.
AB  - 1. Glutamate-NMDA receptor excitotoxicity and oxidative stress are two common
      mechanisms associated with most neurodegenerative diseases. We hypothesize that
      the vital state of neurons is regulated in part by two key transcription factors,
      CREB and NF-kappaB. To test this hypothesis we used hippocampal-entorhinal cortex
      slice cultures. 2. Glutamate neurotoxicity and oxidative stress neurotoxicity,
      using hydrogen peroxide (H(2)O(2)) are both associated with a decrease in CREB
      DNA binding and an increase in NF-kappaB DNA binding. 3. Agents that modulate
      CREB and NF-kappaB DNA-binding activity alter neurotoxicity. Rolipram, a
      phosphodiesterase IV inhibitor, increased CREB DNA binding activity and decreased
      toxicity, whereas TNFalpha, increased NF-kappaB DNA-binding activity and
      increased neurotoxicity to both glutamate and H(2)O(2). Ethanol decreased CREB
      and increased NF-kappaB DNA-binding activity and increased neurotoxicity to both
      glutamate and H(2)O(2). 4. Brain-derived neurotrophic factor (BDNF) is a
      transcriptionally regulated trophic factor whose expression follows sensitivity
      to toxicity suggesting it is one of the transcriptionally regulated factors that
      contributes to neuronal vitality secondary to the balance of CREB-NF-kappaB
      activated transcription. Together these studies suggest that neurotoxicity
      through glutamate-NMDA receptors or oxidative stress is dependent upon CREB and
      NF-kappaB DNA transcription that regulates vitality of neurons.

PMID- 16633892
TI  - The discovery of a novel macrophage binding site.
AB  - 1. During the course of studies directed to determine the transport of
      Angiotensin II AT(2) receptors in the rat brain, we found that stab wounds to the
      brain revealed a binding site recognized by the AT(2) receptor ligand CGP42112
      but not by Angiotensin II. 2. We localized this novel site to
      macrophages/microglia associated with physical or chemical injuries of the brain.
      3. The non-Angiotensin II site was also highly localized to inflammatory lesions
      of peripheral arteries. 4. In rodent tissues, high binding expression was limited
      to the spleen and to circulating monocytes. A high-affinity binding site was also
      characterized in human monocytes. 5. Lack of affinity for many ligands binding to
      known macrophage receptors indicated the possibility that the non-Angiotensin II
      CGP42112 binding corresponds to a novel site.6. CGP42112 enhanced cell attachment
      to fibronectin and collagen and metalloproteinase-9 secretion from human
      monocytes incubated in serum-free medium but did not promote cytokine secretion.
      7. When added in the presence of lipopolysaccharide, CGP42112 reduced the
      lipopolysaccharide-stimulated secretion of the pro-inflammatory cytokines TNF
      alpha, IL-1, IL-1 beta, and IL-6, and increased protein kinase A. 8. Molecular
      modeling revealed that a CGP42112 derivative was selective for the novel
      macrophage site and did not recognize the Angiotensin II AT(2) receptor. 9. These
      results demonstrate that CGP42112, previously considered as a selective
      Angiotensin II AT(2) ligand, recognizes an additional non-Angiotensin II site
      different from AT(2) receptors. 10. Our observations indicate that CGP42112 or
      related molecules could be considered of interest as potential anti-inflammatory
      compounds.

PMID- 16633893
TI  - Corticotropin Releasing Factor (CRF) activation of NF-kappaB-directed
      transcription in leukocytes.
AB  - 1. The aim of this study was to test whether CRF enhanced nuclear factor kappa B
      (NF-kappaB)-directed gene transcription in leukocytes and the receptor
      specificity of the effect. Initially, we examined the ability of CRF to modulate
      an antigen-specific, in vitro antibody response. Since that could be mediated by
      NF-kappaB transcription factor activity, we tested CRF in a NF-kappaB driven
      luciferase gene expression reporter assay. 2. CRF enhanced the antigen-specific
      antibody production in a dose- and time-dependent manner. RAW 264.7 macrophage
      cells and splenocytes stained by immunohistochemistry were positive for CRF
      receptors and CRF. Expression of both was up-regulated by mitogen treatment of
      the splenocytes. CRF also enhanced the NF-kappaB-regulated reporter assay and
      this could be blocked by a CRF-R1 receptor antagonist. 3. In light of these
      findings, it seems likely that CRF enhanced the antigen-specific antibody
      response through the CRF-R1 receptor by elevation of NF-kappaB activity. This
      study provides further support for the concept that CRF can act as an
      immunomodulator mediating neuro-immune interactions.

PMID- 16633894
TI  - The number of proliferating cells in the rostral migratory stream of rat during
      the first postnatal month.
AB  - The objective of this study was to analyze neurogenesis in the rat rostral
      migratory stream (RMS) during the first postnatal month.1. During the early
      postnatal development some morphological changes, concerning the RMS thickness,
      shape, and the olfactory ventricle persistence at P0 were observed. 2.
      Bromodeoxyuridine (BrdU) immunohistochemistry and subsequent quantification of
      proliferating cells showed significant age-dependent changes. The highest number
      of proliferating cells was found at P3 and significant decrease of BrdU-positive
      cells at P7 rats. At P28, the number of proliferating cells reached the level of
      P0 rats.

PMID- 16633896
TI  - Nitric oxide-GAPDH-Siah: a novel cell death cascade.
AB  - 1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant
      glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly
      unrelated functions. Recent studies indicate that it is a major intracellular
      messenger mediating apoptotic cell death. This paper reviews the GAPDH cell death
      cascade and discusses its clinical relevance. 2. A wide range of apoptotic
      stimuli activate NO formation, which S-nitrosylates GAPDH. The S-nitrosylation
      abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah,
      an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. In the nucleus,
      GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected
      target proteins and affect apoptosis. 3. The cytotoxicity of mutant Huntingtin
      (mHtt) requires nuclear translocation which appears to be mediated via a ternary
      complex of GAPDH-Siah-mHtt. The neuroprotective actions of the monoamine oxidase
      inhibitor R-(-)-deprenyl (deprenyl) reflect blockade of GAPDH-Siah binding. Thus,
      novel cytoprotective therapies may emerge from agents that prevent GAPDH-Siah
      binding.

PMID- 16633897
TI  - Bone marrow stem cells and polymer hydrogels--two strategies for spinal cord
      injury repair.
AB  - 1. Emerging clinical studies of treating brain and spinal cord injury (SCI) led
      us to examine the effect of autologous adult stem cell transplantation as well as
      the use of polymer scaffolds in spinal cord regeneration. We compared an
      intravenous injection of mesenchymal stem cells (MSCs) or the injection of a
      freshly prepared mononuclear fraction of bone marrow cells (BMCs) on the
      treatment of an acute or chronic balloon-induced spinal cord compression lesion
      in rats. Based on our experimental studies, autologous BMC implantation has been
      used in a Phase I/II clinical trial in patients (n=20) with a transversal spinal
      cord lesion. 2. MSCs were isolated from rat bone marrow by their adherence to
      plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Macroporous
      hydrogels based on derivatives of 2-hydroxyethyl methacrylate (HEMA) or 2
      hydroxypropyl methacrylamide (HPMA) were prepared, then modified by their
      copolymerization with a hydrolytically degradable crosslinker, N,O
      dimethacryloylhydroxylamine, or by different surface electric charges. Hydrogels
      or hydrogels seeded with MSCs were implanted into rats with hemisected spinal
      cords. 3. Lesioned animals grafted with MSCs or BMCs had smaller lesions 35 days
      postgrafting and higher scores in BBB testing than did control animals and also
      showed a faster recovery of sensitivity in their hind limbs using the plantar
      test. The functional improvement was more pronounced in MSC-treated rats. In MR
      images, the lesion populated by grafted cells appeared as a dark hypointense area
      and was considerably smaller than in control animals. Morphometric measurements
      showed an increase in the volume of spared white matter in cell-treated animals.
      In the clinical trial, we compared intraarterial (via a. vertebralis, n=6) versus
      intravenous administration of BMCs (n=14) in a group of subacute (10-33 days post
      SCI, n=8) and chronic patients (2-18 months, n=12). For patient follow-up we used
      MEP, SEP, MRI, and the ASIA score. Our clinical study revealed that the
      implantation of BMCs into patients is safe, as there were no complications
      following cell administration. Partial improvement in the ASIA score and partial
      recovery of MEP or SEP have been observed in all subacute patients who received
      cells via a. vertebralis (n=4) and in one out of four subacute patients who
      received cells intravenously. Improvement was also found in one chronic patient
      who received cells via a. vertebralis. A much larger population of patients is
      needed before any conclusions can be drawn. The implantation of hydrogels into
      hemisected rat spinal cords showed that cellular ingrowth was most pronounced in
      copolymers of HEMA with a positive surface electric charge. Although most of the
      cells had the morphological properties of connective tissue elements, we found NF
      160-positive axons invading all the implanted hydrogels from both the proximal
      and distal stumps. The biodegradable hydrogels degraded from the border that was
      in direct contact with the spinal cord tissue. They were resorbed by macrophages
      and replaced by newly formed tissue containing connective tissue elements, blood
      vessels, GFAP-positive astrocytic processes, and NF-160-positive neurofilaments.
      Additionally, we implanted hydrogels seeded with nanoparticle-labeled MSCs into
      hemisected rat spinal cords. Hydrogels seeded with MSCs were visible on MR images
      as hypointense areas, and subsequent Prussian blue histological staining
      confirmed positively stained cells within the hydrogels. 4. We conclude that
      treatment with different bone marrow cell populations had a positive effect on
      behavioral outcome and histopathological assessment after SCI in rats; this
      positive effect was most pronounced following MSC treatment. Our clinical study
      suggests a possible positive effect in patients with SCI. Bridging the lesion
      cavity can be an approach for further improving regeneration. Our preclinical
      studies showed that macroporous polymer hydrogels based on derivatives of HEMA or
      HPMA are suitable materials for bridging cavities after SCI; their chemical and
      physical properties can be modified to a specific use, and 3D implants seeded
      with different cell types may facilitate the ingrowth of axons.

PMID- 16633898
TI  - Differential effects of cocaine-induced seizures and lethality on M(1)-like
      muscarinic and dopaminergic D (1)- and D (2)-like binding receptors in mice
      brain.
AB  - This work was designed to study the changes produced by cocaine-induced seizures
      and lethality on dopaminergic D(1)- and D(2)-like receptors, muscarinic M(1)-like
      binding sites, as well as acetylcholinesterase activity in mice prefrontal cortex
      (PFC) and striatum (ST). Binding assays were performed in brain homogenates from
      the PFC and ST and ligands used were [(3)H]-N-methylscopolamine, [(3)H]-NMS (in
      the presence of carbachol), [(3)H]-SCH 23390 and [(3)H]-spiroperidol (in presence
      of mianserin), for muscarinic (M(1)-like), D(1)- and D(2)-like receptors,
      respectively. Brain acetylcholinesterase (AChE) activity was also determined in
      these brain areas. Cocaine-induced SE decreased [(3)H]-SCH 23390 binding in both
      ST and PFC areas. A decrease in [(3)H]-NMS binding and an increase in [(3)H]
      spiroperidol binding in PFC was also observed. Cocaine-induced lethality
      increased [(3)H]-spiroperidol binding in both areas and decreased [(3)H]-NMS
      binding only in PFC, while no difference was seen in [(3)H]-SCH 23390 binding.
      Neither SE, nor lethality altered [(3)H]-NMS binding in ST. AChE activity
      increased after SE in ST while after death the increase occurred in both PFC and
      ST. In conclusion, cocaine-induced SE and lethality produces differential changes
      in brain cholinergic and dopaminergic receptors, depending on the brain area
      studied suggesting an extensive and complex involvement of these with cocaine
      toxicity in central nervous system.

PMID- 16633900
TI  - 14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of
      patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan.
AB  - 1. Sporadic Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal
      disease. Patients with CJD usually become akinetic mutism within approximately 6
      months. In addition, clinical signs and symptoms at early stage of sporadic CJD
      may not be easy to distinguish from other neurodegenerative diseases by
      neurological findings. However, diagnostic biochemical parameters including 14-3
      3 protein, S100, neuron-specific enorase in cerebrospinal fluid (CSF) have been
      used as diagnostic markers, elevated titers of these markers can also be observed
      in CSF in other neurodegenerative diseases. Therefore, we examined other
      biochemical markers to discriminate CJD from other neurodegenerative diseases in
      CSF. 2. We analyzed CSF samples derived from 100 patients with various
      neurodegenerative disorders by Western blot of 14-3-3 protein, quantification of
      total tau (t-tau) protein, and phosphorylated tau (p-tau) protein. All patients
      with CJD in this study showed positive 14-3-3 protein and elevated t-tau protein
      (>1000 pg/mL) in CSF. We also detected positive 14-3-3 protein bands in two
      patients in non-CJD group (patients with dementia of Alzheimer's type; DAT) and
      also detected elevated t-tau protein in three patients in non-CJD group. Elevated
      t-tau protein levels were observed in two patients with DAT and in one patient
      with cerevrovascular disease in acute phase. 3. To distinguish patients with CJD
      from non-CJD patients with elevated t-tau protein in CSF, we compared the ratio
      of p-tau and t-tau proteins. The p-/t-tau ratio was dramatically and
      significantly higher in DAT patients rather than in CJD patients. 4.Therefore, we
      concluded that the assay of t-tau protein may be useful as 1st screening and the
      ratio of p-tau protein/t-tau protein would be useful as 2nd screening to
      discriminate CJD from other neurodegenerative diseases.

PMID- 16633899
TI  - Immunohistochemical, histochemical and radioassay analysis of nitric oxide
      synthase immunoreactivity in the lumbar and sacral dorsal root ganglia of the
      dog.
AB  - In this study, immunohistochemistry for neuronal nitric oxide synthase (bNOS-IR),
      nicotinamide adenine dinucleotide phosphate diaphorase histochemistry (NADPHd)
      and nitric oxide synthase radioassay were used to study the occurrence, number
      and distribution pattern of nitric oxide synthesizing neurons in the lumbar (L1
      L7) and sacral (S1-S3) dorsal root ganglia of the dog. Nitric oxide synthase
      immunolabelling was present in a large number of small- (area <1,000 microm(2))
      and medium-sized (area 1,000-2,000 microm(2)) as well as in a limited number of
      large-sized (area >2000 microm(2)) neurons. Although neuronal nitric oxide
      synthase immunolabelling and histochemical staining provided intense staining of
      multiple small- and medium-sized neurons in all lumbar and sacral dorsal root
      ganglia, immuno-labelled or histochemically stained somata exhibited little
      topographic distribution in individual dorsal root ganglia. Great heterogeneity
      was noticed in the immunolabelling of medium-sized nitric oxide synthase
      immunopositive neurons ranging from lightly immuno-labelled somata to heavily
      immunoreactive ones with completely obscured nuclei. Both staining procedures
      proved to be highly effective in visualizing intraganglionic fibers of various
      diameters. In general, the largest fibers revealed at the peripheral end of
      lumbar and sacral dorsal root ganglia were larger, 6.49-9.35 mum in diameter,
      while those running centrally and proceeding into the dorsal roots were about 30%
      reduced, ranging between 5.32 and 8.67 microm in diameter. Peripherally, the
      occurrence of nitric oxide synthase detected in axonal profiles, and confirmed
      histochemically, in the specimens of the femoral and sciatic nerves, is the first
      indication of the presence of nitric oxide synthase in the peripheral processes
      of somata located in L4-S2 dorsal root ganglia. Large and thin central nitric
      oxide synthase immunoreactive processes of L1-S3 dorsal root ganglion neurons
      segregate shortly before entering the spinal cord, the former making a massive
      medial bundle in the dorsal root accompanied by a slim lateral bundle penetrating
      Lissauer's tract. Quantitative assessment of the distribution of bNOS-IR and/or
      NADPHd-stained neurons showed a peculiar pattern in relation to spinal levels.
      Apparent incongruity was found in the total number of NADPHd-stained versus bNOS
      IR neurons, demonstrating a clear prevalence of small bNOS-IR somata in all
      lumbar ganglia, while medium-sized NADPHd-stained somata clearly prevailed all
      along the rostrocaudal axis with a peak in L5 ganglion. While the number of small
      bNOS-IR neurons clearly outnumbered NADPHd-stained and NADPHd-unstained somata in
      S1-S3 ganglia, an inverse relation appeared comparing the total number of medium
      sized NADPHd-stained and NADPHd-unstained somata compared with the number of
      moderate and intense bNOS-IR neurons. Densitometry of bNOS-IR and NADPHd-stained
      neurons in lumbar and sacral ganglia revealed two distinct subsets of
      densitometric profiles, one relating to more often found medium-sized bNOS immuno
      labelled and the other, characteristic for moderately bNOS immunoreactive somata
      of the same cell size. Considerable differences in catalytic nitric oxide
      synthase activity, determined by conversion of [(3)H]arginine to [(3)H]citrulline
      were obtained in lumbosacral dorsal root ganglia all along the lumbosacral
      intumescence, the lowest (0.898+/- 0.2 dpm/min/microg protein) being in the L4
      dorsal root ganglion and the highest (4.194+/-0.2 dpm/min/microg protein) in the
      S2 dorsal root ganglion.

PMID- 16633901
TI  - Identification and characterization of syntaxin 1 antisense variants in Limulus
      polyphemus.
AB  - 1.A Limulus SMART(TM) cDNA library screening resulted in the cloning of four
      syntaxin 1 homologs (referred to as Limulus syntaxin [Lim-syn] 1A, 1B, 1C, and
      1D) (Wang, Y., Cao, Z., Xu, W., Kemp, M. D., McAdory, B. S., Newkirk, R. F., Ivy,
      M. T., and Townsel, J. G. (2004). Gene 326:189-199) and two novel intron
      retaining syntaxin 1-like variants, designated Limulus syntaxin variant [Lim
      synV] 1A/1C and Lim-synV 1B/1D. 2.The variants exhibited high amino acid sequence
      identity with the four syntaxin 1 homologs. Specifically, Lim-synV 1A/1C and Lim
      synV 1B/1D were homologous to Lim-syn 1A/1C and Lim-syn 1B/1D, respectively.
      Surprisingly, both Lim-synV 1A/1C and 1B/1D are unusual in that each has a poly
      A+ tail, an intron, and the common splice motif "GT-AG" at the intron-exon
      boundary. Exons one and two on the complementary transcript of Lim-synV 1B/1D are
      separated by a 150 bp intron beginning at #95/96 of the predicted sequences for
      Lim-syn 1B and 1D, respectively. 3. In contrast, examination of the approximately
      3.17 kb Lim-synV 1A/1C clone indicated the inclusion of an insert of 1120 base
      pairs (bp) beginning at codon #37/38 of the predicted Lim-syn 1A and 1C cDNAs'
      open reading frames (ORFs). Further, the intron sequence of Lim-synV 1A/C
      contained multiple stop codons and showed no significant homology to other known
      sequences as determined by a search of the GenBank database. Thus, the focus of
      this paper will be Lim-synV 1B/D exclusively. 4. To substantiate that an intron
      is retained in the full-length mRNA, two types of syntaxin cDNA fragments for Lim
      syn 1B/D were generated by RT-PCR and analyzed on Northern blots. The products
      generated were a mixture of intron-retaining, as well as intron-spliced products.
      The syntaxin-like variants that retained the intron presumably are derived from a
      mRNA molecule that has not undergone splicing.5. Although the significance of
      such intron-containing mRNAs in Limulus has not yet been elucidated, future
      studies of such variants may serve to broaden our knowledge concerning
      established splicing mechanisms as well as to focus attention on nonconventional
      concepts about gene product regulation.

PMID- 16633902
TI  - Creatine and antioxidant treatment prevent the inhibition of creatine kinase
      activity and the morphological alterations of C6 glioma cells induced by the
      branched-chain alpha-keto acids accumulating in maple syrup urine disease.
AB  - Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic
      acid (KIC), alpha-keto-beta-methylvaleric acid (KMV), and alpha-ketoisovaleric
      acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) in
      tissues and biological fluids is the biochemical hallmark of patients affected by
      the neurometabolic disorder known as maple syrup urine disease (MSUD).
      Considering that brain energy metabolism is possibly altered in MSUD, the
      objective of this study was to determine creatine kinase (CK) activity, a key
      enzyme of energy homeostasis, in C6 glioma cells exposed to BCKA. The cells were
      incubated with 1, 5, or 10 mM BCKA for 3 h and the CK activity measured
      afterwards. The results indicated that the BCKA significantly inhibited CK
      activity at all tested concentrations. Furthermore, the inhibition caused by the
      BCKA on CK activity was totally prevented by preincubation with the energetic
      substrate creatine and by coincubation with the N-nitro-L-arginine methyl ester
      (L-NAME), a nitric oxide synthase inhibitor, indicating that deficit of energy
      and nitric oxide (NO) are involved in these effects. In contrast, other
      antioxidants such as glutathione (GSH) and trolox (soluble Vitamin E) were not
      able to prevent CK inhibition. In addition, we observed that the C6 cells changed
      their usual rounded morphology when exposed for 3 h to 10 mM BCKA and that
      creatine and L-NAME prevented these morphological alterations. Considering the
      importance of CK for brain metabolism homeostasis, it is conceivable that
      inhibition of this enzyme by increased levels of BCKA may contribute to the
      neurodegeneration of MSUD patients.

PMID- 16633903
TI  - Glutamate uptake is stimulated by extracellular S100B in hippocampal astrocytes.
AB  - 1.S100B is a calcium-binding protein expressed and secreted by astrocytes, which
      has been implicated in glial-neuronal communication. Extracellular S100B appears
      to protect hippocampal neurons against toxic concentrations of glutamate. Here we
      investigated a possible autocrine role of S100B in glutamate uptake activity. 2.
      Astrocyte cultures were prepared of hippocampi from neonate Wistar rats. [(3)H]
      Glutamate uptake was measured after addition of S100B protein, antibody anti
      S100B or TRTK-12, a peptide that blocks S100B activity mediated by the C-terminal
      region. 3.Antibody anti-S100B addition decreased glutamate uptake measured 30 min
      after medium replacement, without affecting cell integrity or viability.
      Moreover, low levels of S100B (less than 0.1 ng/mL) stimulated glutamate uptake
      measured immediately after medium replacement. 4. This finding reinforces the
      importance of astrocytes in the glutamatergic transmission, particularly the role
      of S100B neuroprotection against excitotoxic damage.

PMID- 16633904
TI  - Differential regulation of c-Fos and FosB in the rat brain after amygdala
      kindling.
AB  - Members of the inducible transcription factor Fos family, that are part of the AP
      1 complex that binds to the corresponding promoter site, are implicated in the
      regulation of gene transcription after acute and chronic seizures. However,
      little is known about the temporal expression of the AP-1 transcription factors
      and if individual proteins composing this complex have distinct roles in
      development and maintenance of permanent epilepsy. In this study, the AP-1
      binding capacity, its content of different Fos proteins, and the anatomical
      specificity, were analyzed 2 or 18 h after achieving full kindling in rats. The
      same analysis was performed in fully kindled animal receiving a new stimulus
      after a 3-week pause to determine the extent of stability of the AP-1
      transcription factors. While both c-Fos and FosB were induced in all cortical
      areas after a single stimulus, only FosB-immunoreactivity remained after 18 h. A
      single stimulation to kindled animals left undisturbed for 3 weeks induced a long
      lasting upregulation of AP-1 binding in the frontal cortex, but not in the
      hippocampus suggesting a permanent exposure of AP-1 heterocomplexes in the
      frontal cortex. Supershift assays showed that FosB is the dominant component of
      the long-term AP-1 complex. It is concluded that the AP-1 binding complex in
      fully kindled rats is composed of different proteins, and that FosB-containing AP
      1 complexes mediate long-term effects in the frontal cortex.

PMID- 16633906
TI  - Risk factors for criminal recidivism in older sexual offenders.
AB  - Sexual offenders constitute a substantial proportion of the older male prison
      population. Recent research findings, with potential consequences for risk
      management, indicate that recidivism risk might be lower in older sexual
      offenders. We followed up all adult male sexual offenders released from prison in
      Sweden during 1993-1997 (N=1,303) for criminal reconviction for an average of 8.9
      years. We studied rates of repeat offending (sexual and any violent) by four age
      bands (<25, 25-39, 40-54, and 55+years), and examined whether risk factors for
      recidivism remained stable across age groups. Results showed that recidivism
      rates decreased significantly in older age bands. In addition, the effect of
      certain risk factors varied by age band. These findings on recidivism rates in
      older sexual offenders concur with studies from the United Kingdom, United
      States, and Canada and may suggest some generalizability in Western settings.
      Further research is needed to address underlying mechanisms.

PMID- 16633905
TI  - Hydrogen sulfide and carbon monoxide are in synergy with each other in the
      pathogenesis of recurrent febrile seizures.
AB  - 1. The purpose of the present study was to investigate the interaction between
      hydrogen sulfide (H(2)S) and carbon monoxide (CO) during recurrent febrile
      seizures (FS) 2.H(2)S and CO are important intra- and intercellular messengers,
      regulating various brain functions. Our recent studies showed that both of them
      alleviate the hippocampal damage induced by recurrent FS. In the present study,
      on a rat model of recurrent FS, we found that hydroxylamine (an inhibitor of
      cystathionine b-synthase, CBS) reduced CO level and down regulated heme oxygenase
      (HO-1) expression, while NaHS (a donor of H(2)S) elevated CO level and
      upregulated HO-1 expression. ZnPP-IX (an inhibitor of HO-1) decreased H(2)S
      formation and down regulated CBS expression, while hemin (which increases the
      production of endogenous CO) enhanced H(2)S formation and elevated CBS
      expression. 3. Our data demonstrate that endogenous H(2)S and CO are in synergy
      with each other in recurrent FS.

PMID- 16633907
TI  - Celebrating 20 years of historical papers in Photosynthesis Research.
AB  - This editorial has four goals: (1) to inform the readers of 'Photosynthesis
      Research' about the past of the 'Historical corner'; which began 20 years ago;
      (2) to encourage photosynthesis researchers and historians of science to contact
      me for publishing papers of historical interest; these include: (a) Obituaries
      and Tributes; (b) historical papers on current and past discoveries and
      controversies; (c) history of research in specific laboratories, or in specific
      countries, or at specific conferences; (d) Personal perspectives (not discussed
      any further); (3) to encourage researchers not to discard, but to save
      correspondence and data of their discoveries for the future historians by
      donating them to their Archives, when appropriate (not discussed any further);
      and (4) to reinforce to the readers that the concept of two-light reaction and
      two-pigment system was already there in 1959. I mention here three key papers
      presented at the IXth International Botanical Congress, held at Montreal Canada
      (in August, 1959) prior to the famous April 9, 1960 paper by Robert Hill and Fay
      Bendall on the 'Z-scheme' of photosynthesis, that was based on thermodynamic and
      energetic considerations.

PMID- 16633908
TI  - Benign epithelial ovarian tumours-cancer precursors or markers for ovarian cancer
      risk?
AB  - The natural history of the development of epithelial ovarian cancer remains
      obscure and no effective screening test exists. In several human malignancies
      progression from benign to invasive tumour occurs, but this sequence has not been
      established for epithelial ovarian cancer. We have reviewed epidemiological,
      histopathological and molecular studies of benign epithelial ovarian tumours to
      assess the evidence for and against such a progression in ovarian cancer. These
      data suggest that a diagnosis of a benign ovarian cyst or tumour is associated
      with an increased risk of ovarian cancer later in life. Current evidence also
      suggests that benign serous tumours can progress to low-grade serous cancer and
      that benign mucinous tumours can progress to mucinous cancer. The more common
      high-grade serous ovarian cancers are likely to arise de novo.

PMID- 16633909
TI  - Cancer surveillance and information: balancing public health with privacy and
      confidentiality concerns (United States).
AB  - Rapid advances in informatics and communication technologies are greatly
      expanding the capacity for information capture and transportation. While these
      tools can be used for great good, they also offer new opportunities for those who
      seek to obtain and use information for improper purposes. While issues related to
      identity theft for financial gain garner the most attention, protection of
      privacy in public health endeavors such as cancer surveillance is also a
      significant concern. Some efforts to protect health-related information have had
      unintended consequences detrimental to health research and public health
      practice. Achieving a proper balance between measures to protect privacy and the
      ability to guard and improve public health requires careful consideration and
      development of appropriate policies, regulations and use of technology.

PMID- 16633910
TI  - The future of cancer surveillance.
AB  - Cancer surveillance is entering an exciting era where the scope of its activities
      will be expanded and the amount, quality, and depth of information on cancer will
      be richer and more readily available to practitioners, decision makers and the
      public. This future is being built on a solid history of accomplishment that has
      placed cancer foremost among all chronic diseases in the organization and
      implementation of a systematic and integrated monitoring enterprise that is of
      essential value in both clinical medicine and public health. The future of cancer
      surveillance will be driven not only by innovations in methods of cancer
      surveillance itself, but also by developments in information technology and
      communication and by revolutionary new tools used in the delivery of medical
      care. At the same time, it will be a challenge to ensure levels of privacy and
      confidentiality needed to maintain the public trust. In the Cancer Surveillance
      and Information Summit, a 2004 conference sponsored by C-Change, experts from the
      field and from allied and related disciplines in both the public and private
      sectors met to consider the future of the cancer surveillance enterprise. Seven
      recommendations, detailed in this article, emerged from the conference to guide
      future growth and development. Steps that can and should be taken by all
      individuals and groups involved in cancer surveillance were included. The shared
      view is that cancer surveillance and information is essential to fulfill a vision
      for a future where cancer is prevented, detected early, and either cured or
      managed successfully as a chronic illness.

PMID- 16633911
TI  - Population-based assessment of hospitalizations for neutropenia from chemotherapy
      in older adults with non-Hodgkin's lymphoma (United States).
AB  - OBJECTIVE: To study neutropenia hospitalization (NH) incidence and risk factors
      in a population-based sample of older adults with non-Hodgkin's lymphoma (NHL)
      and evaluate the validity of inferences from Surveillance, Epidemiology and End
      Results (SEER)-Medicare linked databases. METHODS: NHL cases receiving first
      course chemotherapy were identified from Iowa SEER-Medicare. Survival methods
      evaluated NH risk factors. Medical record and Medicare claims data on
      chemotherapy and NH were compared. RESULTS: Of 761 subjects, 165 (21.7%, 95% CI:
      18.8, 24.6) were hospitalized for neutropenia. Of those hospitalized, 41% were
      hospitalized in cycle 1 and 22% in cycle 2. Significant multivariable risk
      factors for NH were diffuse large cell histology, renal disease, Charlson
      comorbidity index, and anthracycline chemotherapy but not patient age. Medicare
      and medical records agreed on month of chemotherapy initiation 95% of the time
      and chemotherapy type 95% of the time. ICD-9 code 288.0 sensitivity for NH was
      80%. CONCLUSIONS: Neutropenia hospitalizations were common in the first 2
      chemotherapy cycles, especially among older adults with comorbidity. Findings
      conflict with a prior medical records study in which age was a risk factor for NH
      and dose intensity a negative confounder. Valid inferences about age effects on
      chemotherapy toxicity require more clinical detail than is available in
      administrative data.

PMID- 16633912
TI  - Cancer and laterality: a study of the five major paired organs (UK).
AB  - OBJECTIVE: The human body displays marked asymmetry: paired organs differ
      bilaterally exerting effects upon cancer incidence and progression. However the
      factors involved remain contentious. In this large study involving over a quarter
      of a million cancer patients, we examine the epidemiological correlates of cancer
      laterality including incidence, stage at diagnosis and survival in the five major
      paired organs: the breasts, lungs, kidneys, testes and ovaries. METHODS: Cancer
      patients were selected from the Thames Cancer Registry database and age
      standardised incidence rates (ASRs), stage distribution at diagnosis and survival
      rates computed, stratifying appropriately. RESULTS: Cancer incidence differed
      significantly by laterality at all sites studied (p < 0.01) but substantially in
      the lung (left-right incidence-rate ratio [IRR] 0.87), breast (IRR 1.07), testis
      (IRR 0.87) and in ovarian cancer (IRR 0.86). Autopsy data showed strongly
      coincident left-right organ size ratios (0.87 in the lungs and 0.87 in the
      testes). Patients with left testicular cancer, right lung cancer and left ovarian
      cancer showed significantly better survival than those with contralateral disease
      (p < 0.05). CONCLUSIONS: In the lungs and testes, asymmetries in cancer incidence
      closely coincided with asymmetries in organ size. Our results suggest that tissue
      mass in these organs is an important contributor to asymmetry in cancer
      incidence.

PMID- 16633913
TI  - Maternal use of recreational drugs and neuroblastoma in offspring: a report from
      the Children's Oncology Group (United States).
AB  - OBJECTIVE: To evaluate whether maternal use of recreational drugs around
      conception and pregnancy influences the risk of childhood neuroblastoma. METHODS:
      Self-reported use of recreational drugs from one month prior to pregnancy until
      diagnosis was assessed among mothers of 538 children with neuroblastoma
      (diagnosed 1992-1994 and identified through the Children's Cancer Group and
      Pediatric Oncology Group) and 504 age-matched controls (identified by random
      digit dialing). Odds ratios (OR) and 95% confidence intervals (CI) were estimated
      using unconditional logistic regression, adjusting for age at diagnosis and
      household income. RESULTS: Maternal use of any illicit or recreational drug
      around pregnancy was associated with an increased risk of neuroblastoma in
      offspring (OR = 1.82, 95% CI: 1.13, 3.00), particularly use of marijuana in the
      first trimester of pregnancy (OR = 4.75, 95% CI: 1.55, 16.48). Marijuana use in
      the month before pregnancy did not increase risk. The effect of gestational
      marijuana exposure was strongest in subjects diagnosed before age one. Evaluation
      of recreational drugs other than marijuana was limited by infrequent use, and
      analyses of drug use by fathers were not carried out due to missing data.
      CONCLUSIONS: Maternal recreational drug use and marijuana use during pregnancy
      were associated with increased risk of neuroblastoma in offspring. Further
      examination of these drugs and the risk of childhood cancer is warranted.

PMID- 16633914
TI  - Patterns of disparity: ethnic and socio-economic trends in breast cancer
      mortality in New Zealand.
AB  - OBJECTIVE: To test whether trends in breast cancer mortality varied by ethnicity
      and socio-economic position during the 1980s and '90s in New Zealand. METHODS:
      Four cohorts of the entire New Zealand population for 1981-84; 86-89; 91-94 and
      96-99 allowed direct determination of socio-economic trends in breast cancer
      mortality. For ethnicity, unlinked routine census and mortality data were used
      with adjustment factors for undercounting of Maori and Pacific deaths. RESULTS:
      Maori and non-Maori non-Pacific mortality rates changed little until mid-1990s
      with Maori experiencing 25% higher mortality. In 1996-99, Maori rates increased
      notably to become 68% higher than non-Maori non-Pacific (SRR 1.68; 95% CI: 1.49
      1.90). Pacific women experienced an approximate three-fold increase in breast
      cancer mortality over time. There appeared to be reducing mortality among higher
      income and education groups but trends within socio-economic groups were not
      statistically significant. Nevertheless, by 1996-99, there was a significant 22%
      excess mortality (SRR 1.22; 95% CI: 1.01-1.49) for low compared with high-income
      groups. CONCLUSIONS: Widening ethnic, and probably, socio-economic disparities in
      breast cancer mortality are likely due to both underlying incidence and
      differential survival trends. Disparities are likely to increase once the full
      differential mortality benefits of screening impact on the population.

PMID- 16633915
TI  - Frequent tanning bed use, weight concerns, and other health risk behaviors in
      adolescent females (United States).
AB  - OBJECTIVE: To examine the association between tanning bed use and weight
      concerns, health risk behaviors, and peer influence. METHODS: The Growing Up
      Today Study (GUTS) is an ongoing prospective cohort study of adolescents
      established in 1996. In 1999, a total of 6,373 adolescent females ages 12-18
      (offspring of participants in the Nurses Health Study 2) completed the survey.
      RESULTS: Almost nine percent (8.6%) of the adolescent girls had used a tanning
      bed 1-9 times and an additional 5.4% had used tanning beds at least 10 times in
      the past year (frequent users). Logistic regression models revealed that frequent
      tanning bed use was associated with being highly concerned about weight (OR =
      1.5, 95%CI = 1.1, 2.0), frequently dieting to lose weight (OR = 1.5, 95%CI = 1.1,
      2.0), using laxatives or vomiting to control weight (OR = 3.6; 95%CI = 2.2-5.8),
      having friends who placed a lot of importance on being thin (OR = 2.6; 95%CI =
      1.3-5.1), smoking cigarettes (OR=1.7, 95%CI = 1.1, 2.6), binge drinking (OR =
      2.1, 95%CI = 1.3, 3.1), using recreational drugs (OR = 3.0; 95%CI = 2.4, 3.8),
      and trying to look like females in the media (sometimes/pretty much: OR = 1.3,
      95%CI = 1.0, 1.8). CONCLUSION: Frequent tanning bed use among adolescent females
      is associated with a range of health risk behaviors. This effect may be mediated
      by peer influence and a desire to look like other females in the media. Multi
      pronged approaches, particularly those that target attitudes of young females,
      are needed to combat increased use of tanning beds.

PMID- 16633916
TI  - Breast-feeding and Wilms tumor: a report from the Children's Oncology Group.
AB  - OBJECTIVE: Previous research has shown that breast-feeding offers many
      nutritional benefits to children including protection against infection and
      possibly a decreased risk of childhood cancer. We investigated the association
      between breast-feeding and Wilms tumor, a childhood kidney tumor. METHODS: We
      used data from a large case-control study in the United States and Canada. Cases
      were children under age 16 years who were diagnosed with Wilms tumor from 1999 to
      2002 and were participating in the National Wilms Tumor Study. Controls were
      identified by random-digit dialing and were age and region matched to cases.
      Mothers of 501 cases and 480 controls provided information on breast-feeding by
      telephone interviews. RESULTS: Breast-feeding was associated with a reduced risk
      of Wilms tumor [adjusted odds ratio (OR) = 0.7; 95% confidence interval (CI) =
      0.5-0.9]. Longer duration did not provide any additional reduction in risk. When
      stratified by maternal education, breast-feeding lowered risk among children
      whose mothers had less than a college education (OR = 0.6; 95% CI = 0.4-0.8) but
      not for mothers who had a college degree or more (OR = 1.1; 95% CI = 0.6-1.9).
      CONCLUSIONS: The results of this study are suggestive of an association between
      breast-feeding and Wilms tumor, but further research is needed to confirm this
      relationship.

PMID- 16633917
TI  - Interactions between body mass index and hormone therapy and postmenopausal
      breast cancer risk (United States).
AB  - OBJECTIVE: To assess interactions between use of estrogen plus progestin hormone
      therapy (EPHT) and body mass index (BMI) in relation to risks of different types
      of breast cancer, based on histology and hormone receptor status. METHODS: We
      conducted a population-based case-control study that compared 975 postmenopausal
      breast cancer cases to 1,007 controls. Interactions between menopausal hormone
      therapy (HT) and BMI in relation to risk of different breast cancer types were
      evaluated using logistic regression. RESULTS: Obese (BMI > or = 30.0 kg/m2) never
      users of HT had 1.7-fold to 2.3-fold elevated risks of ductal and ER+/PR+ tumors,
      respectively, compared to thinner women. BMI was not related to breast cancer
      risk among current HT users. Current EPHT users for > or = 5 years had 2.1 to 9.6
      fold elevated risks of lobular and ER+/PR+ tumors compared to never users of HT
      regardless of BMI. Current EPHT users for > or = 5 years with a BMI < or = 24.9
      kg/m2 also had a 2.6-fold elevated risk of ductal carcinoma. However, none of the
      interactions between BMI and HT use evaluated reached statistical significance.
      CONCLUSIONS: While interactions between HT and BMI are well established, they
      appear to only be present among certain breast cancer types. Since obesity is
      related to breast cancer risk only among never users of HT, as HT use declines
      the relative impact of obesity on breast cancer incidence may grow.

PMID- 16633918
TI  - Beliefs about tobacco industry (mal)practices and youth smoking behaviour:
      insight for future tobacco control campaigns (Canada).
AB  - OBJECTIVE: To examine how student beliefs about tobacco industry behaviour and
      marketing practices were related to occasional and regular smoking among 9th to
      12th graders. These findings can provide insight for developing new tobacco
      industry denormalization messages for youth smoking populations. METHODS: Cross
      sectional data were collected from 14,767 grade 9 to 12 students attending 22
      secondary schools within one Public Health Region of Canada using the Tobacco
      Module of School Heath Action, Planning and Evaluation System (SHAPES). Logistic
      regression analyses were used to determine if different beliefs about tobacco
      companies were able to differentiate never smokers from occasional smokers, and
      occasional smokers from regular smokers. RESULTS: Occasional and regular smoking
      behaviour was significantly related to student beliefs about tobacco companies
      doing good things in the community, manipulating young people to think smoking is
      cool, advertising to youth, and using athletes and sports sponsorships to get
      young people to smoke. CONCLUSIONS: This study identified that beliefs about
      tobacco industry behaviour and marketing practices were related to youth smoking
      behaviour. In order to address the unique needs of smoking youth, discussions for
      future tobacco industry denormalization campaigns should consider messages
      tailored to focus on corporate social responsibility, sport and cultural event
      sponsorship and industry manipulation.

PMID- 16633919
TI  - Body size and risk of epithelial ovarian cancer (United States).
AB  - OBJECTIVE: We conducted a population-based case-control study of epithelial
      ovarian cancer in relation to measures of body size and adult weight change. In
      particular, we sought to characterize the independent relation of body weight at
      particular ages with risk. METHODS: In-person interviews were sought with 35-54
      year-old female residents of metropolitan Atlanta, Seattle or Detroit diagnosed
      with ovarian cancer during 1994-1998, and with controls sampled from these
      populations. Information provided by 355 cases and 1,637 controls was analyzed
      using unconditional logistic regression. RESULTS: The risk among women in the top
      tenth, relative to women in the lowest fourth, of the distribution of body weight
      at age 18 years was 1.5 (95% confidence interval, 1.0-2.2); at age 30, 1.9 (1.2
      2.9); and 5 years before the reference date, it was 2.1 (1.4-3.3). While our
      results did not substantiate risk elevations reported in previous studies among
      subsets of women (e.g., with particular histologic tumor subtypes or according to
      past oral contraceptive use), we noted a particularly increased risk among women
      who reported 10 or more pounds gained during their first year of oral
      contraceptive use. CONCLUSIONS: Our findings suggest that risk of epithelial
      ovarian cancer may be most closely linked with body weight in the relatively
      recent past (but before the time in which the disease may manifest as weight
      loss) among women who develop this disease during the years before or shortly
      after menopause.

PMID- 16633920
TI  - O6-methylguanine-DNA methyltransferase Leu84Phe and Ile143Val polymorphisms and
      risk of colorectal cancer in the Nurses' Health Study and Physicians' Health
      Study (United States).
AB  - OBJECTIVE: O6-methylguanine-DNA methyltransferase (MGMT) removes mutagenic
      adducts from the O6-position of guanine in DNA. Unrepaired O6-methylguanines
      result in G:C to A:T transitions in mutated K-ras and p53 in colorectal tumors.
      Two non-synonymous MGMT coding region variants, Leu84Phe and Ile143Val, lie in
      close proximity to the reactive 145Cys residue and to a conserved estrogen
      receptor interacting helix. METHODS: We assessed the association between the MGMT
      Leu84Phe and Ile143Val polymorphisms and risk of colorectal cancer in two nested
      case-control studies: one each in the Nurses' Health Study (NHS) and the
      Physicians' Health Study (PHS) cohorts. RESULTS: Among 197 female cases and 2,500
      controls from the NHS, the variant 143Val allele was significantly associated
      with reduced risk of colorectal cancer [odds ratio (OR) = 0.52, 95% confidence
      interval (CI) 0.33-0.80]. In women, statistically significant gene-environment
      interactions were found between the Leu84Phe polymorphism and alcohol intake (P =
      0.03), BMI (P = 0.04) and postmenopausal hormone use (P = 0.03). The Leu84Phe and
      Ile143Val polymorphisms were not significantly associated with risk of colorectal
      cancer among 271 male cases and 451 controls from the PHS. CONCLUSIONS: Our
      results suggest that the common Leu84Phe and Ile143Val polymorphisms in MGMT
      influence risk of colorectal cancer in women possibly through modulating estrogen
      receptor-dependent transcriptional activation, which has previously been shown to
      occur in response to DNA alkylation damage.

PMID- 16633921
TI  - Celebremos la salud! a community randomized trial of cancer prevention (United
      States).
AB  - BACKGROUND: Compared to non-Hispanic whites, Hispanics in the United States are
      at higher risk for certain types of cancer. METHODS: In a randomized controlled
      trial of 20 communities, we examined whether a comprehensive intervention
      influenced cancer screening behaviors and lifestyle practices in rural
      communities in Eastern Washington State. Cross-sectional surveys at baseline and
      post-intervention included interviews with a random sample of approximately 100
      households per community. The interview included questions on ever use and recent
      use of Pap test, mammogram, and fecal occult blood test (FOBT) and
      sigmoidoscopy/colonoscopy, fruit and vegetable consumption and smoking practices.
      RESULTS: We found few significant changes in use of screening services for
      cervical (Pap test), breast (mammogram) or colorectal cancer (fecal occult blood
      test (FOBT) or sigmoidoscopy/colonoscopy) between intervention and control
      communities. We found no significant differences in fruit and vegetable
      consumption nor in smoking prevalence between the two groups. We found more
      awareness of and participation in intervention activities in the treatment
      communities than the control communities. CONCLUSIONS: Our null findings might be
      attributable to the low dose of the intervention, a cohort effect, or
      contamination of the effect in non-intervention communities. Further research to
      identify effective strategies to improve cancer prevention lifestyle behaviors
      and screening practices are needed.

PMID- 16633922
TI  - Re: Glaser et al. Increased training and funding for cancer surveillance research
      and argues that cancer registry data are underutilized.

PMID- 16633923
TI  - Guidelines for the proper use of etanercept in Japan.
AB  - Application of biological agents targeting inflammatory cytokines such as tumor
      necrosis factor-alpha (TNF-alpha) dramatically caused a paradigm shift in the
      treatment of rheumatoid arthritis (RA). Infliximab, a chimeric anti-TNF-alpha
      monoclonal antibody, has initially been introduced to Japan in 2003 and shown to
      be dramatically effective in alleviating arthritis refractory to conventional
      treatment. However, serious adverse events such as bacterial pneumonia,
      tuberculosis, and Pneumocystis jiroveci pneumonia were reported to be in
      relatively high incidence; i.e., 2%, 0.3%, and 0.4%, respectively, in a strict
      postmarketing surveillance of an initial 4000 cases in Japan. Etancercept, a
      recombinant chimeric protein consisting of p75 TNF-alpha receptor and human IgG,
      was subsequently introduced to Japan in March of 2005. We therefore drew up
      treatment guidelines for the use of etanercept to avoid potential serous adverse
      events, since only approximately 150 cases have been included in the clinical
      study of etanercept in Japan. The guidelines were initially designed by the
      principal investigators (N.M, T.T., K.E.) of rheumatoid arthritis study groups of
      the Ministry of Health, Labor and Welfare (MHLW), Japan, and finally approved by
      the board of directors of the Japan College of Rheumatology. The MHLW assigned a
      duty to the pharmaceutical companies to perform a complete postmarketing
      surveillance of an initial 3000 cases to explore any adverse events, and this was
      performed according to the treatment guidelines shown in this article.

PMID- 16633924
TI  - The role of c-Src kinase in the regulation of osteoclast function.
AB  - The targeted disruption of c-Src impairs osteoclast bone resorbing activity,
      causing osteopetrosis. Although it has been reported that restoring only the c
      Src adaptor function at least partly rescues the skeletal phenotypes, the
      importance of c-Src kinase activity remains controversial. We here highlight the
      contributions of the Src adaptor and kinase activities in cytoskeletal
      organization and osteoclast function using adenovirus vectors containing various
      mutants of Src or Pyk2. In addition, we describe the importance of c-Src in
      mitochondria, where it phosphorylates cytochrome c oxidase (Cox). Src-induced Cox
      activity is also required for bone resorbing activity of osteoclasts that require
      high levels of ATP. Thus, c-Src kinase activity not only on the plasma membrane
      but also within mitochondria is essential for the regulation of osteoclastic bone
      resorption.

PMID- 16633925
TI  - Potential impact of observational cohort studies in Japan on rheumatoid arthritis
      research and practice.
AB  - For better management of rheumatoid arthritis (RA) patients, we need information
      both from well-designed clinical trials, such as randomized controlled trials,
      and from observational cohorts. Observational cohort study has not been developed
      in Japanese RA patients; however, two cohorts, IORRA (formerly J-ARAMIS) from
      2000 and NinJa by iR-net from 2002, have been established. These two cohorts are
      an important source not only for better management of Japanese RA patients but
      also for solutions to a variety of issues concerning RA clinical practice in
      general. In this minireview, necessities of observational cohort studies are
      discussed.

PMID- 16633926
TI  - Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid
      arthritis in Japan: a preliminary analysis.
AB  - The tumor necrosis factor (TNF) antagonist etanercept is an antirheumatic agent
      which was approved by Japanese regulatory authorities in January 2005. In Japan,
      the cost-effectiveness of this therapy for patients with rheumatoid arthritis
      (RA) has not previously been evaluated. This study models the cost-utility of
      etanercept in comparison with standard therapy with disease-modifying
      antirheumatic drugs (DMARDs) among adult Japanese RA patients who have failed a
      previous course of the DMARD bucillamine. A Markov model with 6-month cycles was
      constructed to compare two therapeutic strategies: etanercept versus standard
      therapy. For each cycle, one of three options was possible: a patient could (i)
      remain on current therapy if American College of Rheumatology criteria for 20%
      clinical improvement (ACR20) were achieved, (ii) switch to another drug in the
      therapeutic pathway if ACR20 was not achieved or if side effects severe enough to
      cause treatment discontinuation occurred, or (iii) they could die. The
      therapeutic pathway for the etanercept strategy was etanercept, methotrexate
      (MTX), sulfasalazine (SSZ), combination therapy (MTX + SSZ) and, finally, no
      DMARD. The pathway for standard therapy was identical except the initial therapy
      was MTX (etanercept was excluded). Results from clinical trials in U.S. and
      European patient populations were used to derive model probabilities for disease
      progression, response to drug therapy, and relationships between ACR20 response
      and functional improvement as measured by the Health Assessment Questionnaire
      (HAQ) disability index. An equation was developed to predict utility from HAQ
      scores of Japanese patients. Costs for drugs and medical services in Japan were
      obtained for April 2003. Analysis was conducted from a societal perspective,
      including lost productivity costs due to RA disability and premature mortality.
      Costs were discounted at 6% annually, and quality-adjusted life years (QALYs) at
      1.5% annually. Model parameters were varied by 20% above and below base-case
      values in sensitivity analyses. Compared to standard therapy, the etanercept
      strategy was yen6.39 million more costly per patient but yielded an additional
      2.56 QALYs. The incremental cost-utility ratio was yen 2.50 million/QALY.
      Sensitivity analyses revealed that cost-utility was most strongly influenced by
      the acquisition cost of etanercept and the percentage of etanercept recipients
      who achieved ACR20. Using commonly applied thresholds for acceptable cost
      effectiveness in the United States ($50 000 = yen 5.5 million/QALY) and the
      United Kingdom (pound 30 000 = yen 5.7 million/QALY), etanercept therapy in Japan
      can be considered cost-effective. Cost-utility ratios did not exceed these
      thresholds in any sensitivity analysis. Further analyses should be conducted once
      clinical and epidemiologic data for Japanese patients become available.

PMID- 16633927
TI  - Efficacy and safety of bucillamine, a D-penicillamine analogue, in patients with
      active rheumatoid arthritis.
AB  - Japanese rheumatologists consider bucillamine (Buc) to be a useful disease
      modifying antirheumatic drug (DMARD) and often give Buc to patients with
      rheumatoid arthritis (RA) prior to administering methotrexate (MTX). However, no
      large studies on the efficacy and safety of Buc in RA patients have been
      published in English to date. We therefore investigated the clinical course of RA
      patients treated with Buc and compared the results with those for patients
      treated with MTX to evaluate and confirm the place of Buc in therapeutic
      strategies for RA in Japan. Our results suggested that Buc should be given to
      patients with moderately active RA either before or after the administration of
      MTX because its efficacy can be judged within 3 months and because serious
      adverse events are rare. Issues like the ability of Buc to prevent joint
      destruction and its efficacy and safety when combined with agents like etanercept
      require future study.

PMID- 16633928
TI  - A case of idiopathic portal hypertension associated with rheumatoid arthritis.
AB  - A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to
      have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as
      having idiopathic portal hypertension on the basis of liver biopsy and
      angiography. Treatment with prednisolone was not sufficiently effective for
      thrombocytopenia. After transabdominal devascularization with splenectomy,
      thrombocytopenia subsided and gastric varices disappeared. In this case, the
      autoimmune mechanism as well as hypersplenism was suspected of being involved in
      the mechanism of thrombocytopenia.

PMID- 16633929
TI  - A case of possible Behcet's disease, preceded by recurrent knee arthropathy for 5
      years, effectively treated with oral colchicine.
AB  - We report a case of possible Behcet's disease (BD) preceded by arthropathy for 5
      years. A 29-year-old man experienced right knee swelling and pain since April
      1999. Thorough examinations were performed, yet a diagnosis was not established.
      In December 2004 he experienced recurrent aphtha, following folliculitis-like
      skin lesions. A human leukocyte antigen examination revealed a positive B51
      allele and his illness was diagnosed as possible Behcet disease. Colchicine was
      administered and his symptoms were ameliorated.

PMID- 16633930
TI  - Expansion of large granular lymphocytes following Pseudomonas infection in a
      patient with adult-onset Still's disease.
AB  - We report a patient who had a 4-year history of adult-onset Still's disease
      (AOSD) and showed a prominent increase in large granular lymphocytes (LGL) when
      she developed severe Pseudomonas conjunctivitis due to Pseudomonas aeruginosa,
      skin eruptions, liver damage, and abnormal findings in coagulation studies,
      without any evidence of active viral activation, hemophagocytosis, or
      malignancies. The increased LGL cells were CD3(+)CD8(+), and disappeared promptly
      after the administration of antibiotics combined with prednisolone, with
      subsequent stabilization of her general condition.

PMID- 16633931
TI  - Subchondral insufficiency fracture of the femoral head after total knee
      arthroplasty in a patient with rheumatoid arthritis.
AB  - We report an 80-year-old woman with rheumatoid arthritis (RA) who was found to
      have subchondral insufficiency fracture of the right femoral head after total
      knee arthroplasty (TKA). Initially, plain radiographs showed no obvious changes,
      but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low
      intensity band on T1-weighted images of the right hip. She underwent
      hemiarthroplasty of the hip. This report describes a rare case of subchondral
      insufficiency fracture of the femoral head after TKA in a patient with RA.

PMID- 16633932
TI  - A case of systemic lupus erythematosus complicated by pure red cell aplasia and
      idiopathic portal hypertension after thymectomy.
AB  - We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia
      (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension
      (IPH) that developed following a thymectomy. She underwent a thymectomy at 40
      years of age to treat myasthenia gravis. PRCA developed 3 years after the
      thymectomy and she was successfully treated with cyclosporin. Systemic lupus
      erythematosus and IPH were diagnosed 6 years later. We conclude that
      immunological dysfunction resulting from the thymectomy contributed significantly
      to the subsequent development of PRCA, SLE, and IPH in this patient. This is the
      first report to describe this extremely rare occurrence.

PMID- 16633933
TI  - Stevens-Johnson syndrome induced by mizoribine in a patient with systemic lupus
      erythematosus.
AB  - A 32-year-old Japanese woman, who had a treatment history of systemic lupus
      erythematosus (SLE) with lupus nephritis World Health Organization class IV for
      11 months, visited our hospital due to fever, facial erythema, and erosion of the
      oral cavity on November 10, 2003. Her mucosal erosion and facial skin erythema
      progressed over the following week, and Stevens-Johnson syndrome was diagnosed
      due to pathological findings of the skin. Among the administrated drugs, only
      mizoribine, started 6 months earlier, produced a positive reaction in the drug
      lymphocyte stimulation test. Increased prednisolone and high dose intravenous
      gamma-globulin were given successfully. Cyclosporine at 50 mg was administered to
      control the SLE, followed by an increase to 100 mg on January 7, 2004. She
      suffered from abdominal pain, blindness, and convulsion on January 9. The
      magnetic resonance image of her brain prompted a diagnosis of reversible
      posterior leukoencephalopathy syndrome. After withdrawal of cyclosporine and
      control of hypertension, symptoms disappeared rapidly. Cyclophosphamide pulse
      therapy was successfully administrated to control lupus nephritis. This is the
      first report describing the relationship between Stevens-Johnson syndrome and
      mizoribine. Although the use of mizoribine is thought to be safe, careful
      observation is necessary.

PMID- 16633934
TI  - Pseudogout attack induced during etidronate disodium therapy.
AB  - We report the first case of pseudogout attack in the distal interphalangeal (DIP)
      joints during etidronate disodium therapy. A 64-year-old woman had intermittent
      administration of etidronate disodium (Didronel; Sumitomo, Osaka, Japan) alone
      because of osteoporosis. Each cycle consisted of a daily dose of 200 mg for 2
      weeks, repeating every 12 weeks. Two weeks after completing the third cycle,
      severe pain and swelling occurred in the DIP joints of the right middle, ring,
      and left ring finger; and skin ulcer formation was observed on the dorsal side of
      the DIP joints of the right middle and ring fingers as well as the left ring
      finger. Because monoclinic calcium pyrophosphate crystals were detected in the
      synovial fluid from the DIP joints of the right middle finger, we diagnosed these
      symptoms as induced by pseudogout attack. Oral loxoprofen sodium at a daily dose
      of 180 mg resulted in rapid symptom resolution. A decrease in function of calcium
      metabolism in elderly persons has been reported to be a cause of pseudogout
      attack. On the other hand, distal interphalangeal joint arthritis presenting as
      Heberden's nodes is a common condition in elderly patients. Therefore, pseudogout
      attack should be considered as an adverse drug reaction when administering
      bisphosphonate in elderly patients with Heberden's nodes.

PMID- 16633935
TI  - Takayasu arteritis associated with systemic sclerosis.

PMID- 16633936
TI  - The most likely voltage path and large deviations approximations for integrate
      and-fire neurons.
AB  - We develop theory and numerical methods for computing the most likely
      subthreshold voltage path of a noisy integrate-and-fire (IF) neuron, given
      observations of the neuron's superthreshold spiking activity. This optimal
      voltage path satisfies a second-order ordinary differential (Euler-Lagrange)
      equation which may be solved analytically in a number of special cases, and which
      may be solved numerically in general via a simple "shooting" algorithm. Our
      results are applicable for both linear and nonlinear subthreshold dynamics, and
      in certain cases may be extended to correlated subthreshold noise sources. We
      also show how this optimal voltage may be used to obtain approximations to (1)
      the likelihood that an IF cell with a given set of parameters was responsible for
      the observed spike train; and (2) the instantaneous firing rate and interspike
      interval distribution of a given noisy IF cell. The latter probability
      approximations are based on the classical Freidlin-Wentzell theory of large
      deviations principles for stochastic differential equations. We close by
      comparing this most likely voltage path to the true observed subthreshold voltage
      trace in a case when intracellular voltage recordings are available in vitro.

PMID- 16633937
TI  - A model that integrates eye velocity commands to keep track of smooth eye
      displacements.
AB  - Past results have reported conflicting findings on the oculomotor system's
      ability to keep track of smooth eye movements in darkness. Whereas some results
      indicate that saccades cannot compensate for smooth eye displacements, others
      report that memory-guided saccades during smooth pursuit are spatially correct.
      Recently, it was shown that the amount of time before the saccade made a
      difference: short-latency saccades were retinotopically coded, whereas long
      latency saccades were spatially coded. Here, we propose a model of the saccadic
      system that can explain the available experimental data. The novel part of this
      model consists of a delayed integration of efferent smooth eye velocity commands.
      Two alternative physiologically realistic neural mechanisms for this integration
      stage are proposed. Model simulations accurately reproduced prior findings. Thus,
      this model reconciles the earlier contradictory reports from the literature about
      compensation for smooth eye movements before saccades because it involves a slow
      integration process.

PMID- 16633938
TI  - Predicting spike timing of neocortical pyramidal neurons by simple threshold
      models.
AB  - Neurons generate spikes reliably with millisecond precision if driven by a
      fluctuating current--is it then possible to predict the spike timing knowing the
      input? We determined parameters of an adapting threshold model using data
      recorded in vitro from 24 layer 5 pyramidal neurons from rat somatosensory
      cortex, stimulated intracellularly by a fluctuating current simulating synaptic
      bombardment in vivo. The model generates output spikes whenever the membrane
      voltage (a filtered version of the input current) reaches a dynamic threshold. We
      find that for input currents with large fluctuation amplitude, up to 75% of the
      spike times can be predicted with a precision of +/-2 ms. Some of the intrinsic
      neuronal unreliability can be accounted for by a noisy threshold mechanism. Our
      results suggest that, under random current injection into the soma, (i) neuronal
      behavior in the subthreshold regime can be well approximated by a simple linear
      filter; and (ii) most of the nonlinearities are captured by a simple threshold
      process.

PMID- 16633939
TI  - Sound representation methods for spectro-temporal receptive field estimation.
AB  - The spectro-temporal receptive field (STRF) of an auditory neuron describes the
      linear relationship between the sound stimulus in a time-frequency representation
      and the neural response. Time-frequency representations of a sound in turn
      require a nonlinear operation on the sound pressure waveform and many different
      forms for this non-linear transformation are possible. Here, we systematically
      investigated the effects of four factors in the non-linear step in the STRF
      model: the choice of logarithmic or linear filter frequency spacing, the time
      frequency scale, stimulus amplitude compression and adaptive gain control. We
      quantified the goodness of fit of these different STRF models on data obtained
      from auditory neurons in the songbird midbrain and forebrain. We found that
      adaptive gain control and the correct stimulus amplitude compression scheme are
      paramount to correctly modelling neurons. The time-frequency scale and frequency
      spacing also affected the goodness of fit of the model but to a lesser extent and
      the optimal values were stimulus dependent.

PMID- 16633940
TI  - Cortical modulation of dorsal column nuclei: a computational study.
AB  - We present a computational study aimed at exploring the sensorimotor cortex
      modulation of the behaviour of dorsal column nuclei, specifically the impact of
      synaptic parameters, during both sleep and waking conditions. On the basis of the
      circuit proposed by Canedo et al. (2000), we have developed realistic
      computational models that have been tested with simultaneous
      electrocorticographic as well as intracellular cuneate recordings performed in
      anaesthetized cats. The results show that, (1) under sleep conditions, the model
      can block the transmission of afferent sensory information and, (2) operations
      expected during wakefulness, such as filtering and facilitation, can be performed
      if synaptic parameters are appropriately tuned.

PMID- 16633945
TI  - The role of statins in clinical medicine--LDL--cholesterol lowering and beyond.
AB  - In the past years, statins have emerged as the most important class of lipid
      lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate
      limiting step of cholesterol synthesis, which leads to upregulation of LDL
      receptors on the cell membrane and thus reduction of atherogenic LDLs. This
      effect translates into clinical benefit by reducing cardiovascular events both in
      primary and secondary prevention settings. As an approximate rule, statin therapy
      leads to a relative risk reduction of 25-30% in most of the large randomised
      controlled trials. Stroke risk is reduced to a similar degree. Despite initial
      concerns, the currently available statins have a favourable safety profile;
      however, potential interactions with other drugs must be considered. Recently,
      characteristics unrelated to LDL lowering have been intensively studied. These
      pleiotropic statin effects result from decreased levels of isoprenoid
      intermediates of cholesterol synthesis. They include--among others--anti
      inflammatory, anti-proliferative, and immunomodulatory actions. Pleiotropic
      effects favourably influence pathomechanisms of plaque formation. Furthermore,
      they may prove beneficial in the prevention or treatment of diseases unrelated to
      atherosclerosis, eg rheumatoid arthritis, multiple sclerosis, or cancer.

PMID- 16633946
TI  - Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss
      Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997
      2003.
AB  - In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation
      (STABMT) initiated a mandatory national registry for all haematopoietic stem cell
      transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010
      patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT)
      and 616 additional re-transplants. This included 1167 male and 843 female
      patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications
      were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid
      tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis
      1,263 patients were alive (63%), 747 had died (37%). Probability of survival,
      transplant related mortality or relapse at 5 years was 52%, 21%, 36% for
      allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication,
      donor type, stem cell source and age of patient. HSCT is an established therapy
      in Switzerland. These data describe current practice and outcome.

PMID- 16633947
TI  - Hospital patients' preferences for involvement in decision-making. A
      questionnaire survey of 1040 patients from a Swiss university hospital.
AB  - OBJECTIVES: Assessing patients' preferences for shared decision-making and
      receiving information. DESIGN: Cross-sectional cohort study. SETTING: University
      Hospital in Northwest Switzerland. PARTICIPANTS: 1825 in-patients (mean age: 58
      years, 48.7% female) were asked to participate, 1040 patients responded (59%).
      MAIN OUTCOME MEASURES: Proportion of positive answers to two questions depicting
      typical elements of shared decision-making plus a question asking for patients'
      information needs. These questions were embedded in a questionnaire sent to
      patients two weeks after discharge from the hospital, asking for perceived
      deficits during their hospital stay and socio-demographic characteristics.
      RESULTS: 779/947 (79.1%) agreed to the statement: "One should stick to the
      physician's advice even if one is not fully convinced of his ideas". 620/945
      (65.6%) agreed to the statement: "It should completely be left to physicians to
      decide on a patient's treatment." 914/952 (96%) agreed to the statement: "Even
      when the news is bad the patient must be informed." Older patients and less
      educated patients are more likely to agree with the first two statements,
      patients with a non-Swiss cultural background favour the information needs
      statement slightly less than other patients (92.4 vs 96.7% agreement). The
      severity of illness had no influence on agreeing or not. However, patients who
      disagreed on any statement were more likely to report a lack of information from
      the hospital. CONCLUSIONS: A substantial number of patients in this study wanted
      the physician to take medical decisions. Yet, almost all patients wanted honest
      information about their health status. Health professionals have to find out to
      what extent an individual patient wants to be involved in decision-making.

PMID- 16633949
TI  - Immunity after organ transplantation.
AB  - After organ transplantation an immunosuppressive regimen is required to prevent
      graft rejection. Immunosuppressive drugs inhibit immune function by targeting
      both T- and B-cell responses through blockage of cellular proliferation induced
      by alloantigen stimulation, and by inhibition of the cytokine production
      necessary for such stimulation. However, the absence of discrimination between
      the immune response against alloantigen from the transplanted organ and the
      immune response against environmental antigens renders transplanted patients
      strongly immunodeficient and susceptible to bacterial and viral infection.
      Optimising the immunosuppressive drug regimen to balance mandatory
      immunosuppression while preserving immunity is a difficult challenge for
      clinicians in charge of transplanted patients. The development and optimisation
      of assays to monitor the current state of an immune response is of great
      interest. This article reviews the mechanisms of the alloimmune response against
      the transplanted organ and the consequences of immunosuppression for the
      patient's immunity. The development and optimisation of assays for monitoring the
      current status of the immune response after organ transplantation is discussed,
      as are novel therapeutic approaches based on induction of tolerance and cellular
      therapy.

PMID- 16633948
TI  - Lymph node enlargement during combination therapy for chronic hepatitis C with
      pegylated interferon alpha and ribavirin: harmless reaction or harmful disease?
AB  - BACKGROUND: Perihepatic lymph node enlargement (LNE) is often present in patients
      with chronic hepatitis C (CHC) and correlates with the degree of inflammation, as
      well as the stage of fibrosis of the liver. LNE at sites distant from the liver
      hilum, however, is not a common feature of chronic hepatitis but may occur during
      antiviral therapy as we report here. OBJECTIVES: The aim of this study was to
      examine the frequency and aetiology of LNE at sites distant from the liver hilum
      in patients with chronic hepatitis C during combination therapy with pegylated
      interferon alpha and ribavirin. METHODS: The charts of all patients undergoing
      therapy with PEG and RIBA for CHC at our institution from January 2002 to April
      2003 were reviewed for those who developed de novo LNE at sites distant from the
      liver hilum. RESULTS: In total, 8/217 patients (3.7%) or 5/125 patients treated
      within clinical trials (4.0%) were recorded to have developed de novo LNE during
      antiviral therapy. CONCLUSION: LNE at various sites distant from the liver hilum
      was observed in up to 4% of our patients during treatment of CHC with PEG and
      RIBA. While being reactive in nature and resolving upon cessation of therapy in
      the majority of patients de novo LNE may be due to serious disease and warrants
      further investigations.

PMID- 16633950
TI  - A stepwise drug treatment algorithm to obtain complete remission in depression: a
      Geneva study.
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: We describe the proportion of severely
      depressed outpatients reaching complete remission at the different stages of a
      drug treatment algorithm. We compare several treatment options for SSRI
      (selective serotonin reuptake inhibitor) non-responders and test the feasibility
      of the algorithm in clinical conditions. METHODS: Patients with severe depressive
      disorders (ICD-10; MADRS > or = 25) admitted to an academic outpatient clinic
      were enrolled in this algorithm-guided sequential treatment protocol (starting
      with an SSRI and ending with a tricyclic, lithium, triodothyronine combination).
      The general principle of the algorithm was to boost the drug therapy in the event
      of non-response. RESULTS: 135 patients entered the study and 131 were eligible
      for analysis. From this group, 86 patients dropped out (65.6%), 40 reached
      complete remission (30.5%) and 5 patients did not reach remission at all (3.8%).
      In the 117 patients to whom a last observation carried forward approach was
      applied, the median improvement of the MADRS score was 48.0% (range -20.7%-100%),
      with 48.7% of patients considered responders, 23.1% partial responders and 28.2%
      non-responders. Median retention time was 8 weeks (range 2-34). CONCLUSIONS: This
      algorithm-guided antidepressant treatment was acceptable for clinicians and
      resulted in an elevated final response rate among study completers. However, the
      dropout rate was high, mainly due to treatment interruption or non-observance.

PMID- 16633951
TI  - Surgical repair of hard palate cleft with absorbable membrane: the new surgical
      technique and its clinical application.
AB  - This study evaluated a new surgical technique with absorbable membrane to repair
      hard palate cleft without extensive mobilisation of the mucoperiosteum. From 2001
      to 2002, 32 selected patients with complete unilateral clefts underwent this
      surgical operation. The traditional flap surgical operation was performed at the
      soft palate, uvula and anterior alveolar cleft. The absorbable membrane was
      implanted to the hard palate cleft gap to guide the regeneration of the
      mucoperiosteum. The patients were followed up for 1-6 months after the operation.
      The speech assessment was carried out 12 months after the operation. Of 32
      patients, 30 were successfully operated by this method and no obvious
      complications occurred. Primary healing on tissue defect of hard palate was
      obtained in 27 patients and secondary healing in 3 patients. Eighty percent of
      the 30 patients had good or excellent speech 12 months after the operation. The
      operation failed in 2 patients. The surgical technique with absorbable membrane
      to repair hard palate appears to have several valuable advantages including the
      decreased area of the hard palate involved and favourable outcome for speech in
      the majority of cases.

PMID- 16633952
TI  - Reliability and validity of a German asthma quality of life questionnaire.
AB  - The Asthma Quality of Life Questionnaire (University of Sydney [AQLQ-Sydney]) is
      a self-administered questionnaire that has been developed in Australia and
      validated in different languages in Australia, the USA and Spain. We developed a
      German translation of this questionnaire by applying a sequential forward and
      backward translation approach. The objective of this study was to validate a
      German translation of the AQLQ-Sydney questionnaire in an outpatient population
      of asthmatic patients in Switzerland. Outpatients were assessed for a diagnosis
      of asthma and those who consented were selected for the validation study. All
      patients had spirometry, methacholine challenge testing, fractional exhaled
      nitric oxide recorded and answered the German AQLQ-Sydney. A subgroup of 17
      patients answered the questionnaire for a second time after receiving asthma
      treatment with combined steroids and bronchodilators for two months. Test-retest
      reliability was tested in 12 stable asthmatic patients without treatment
      modification. Of 90 patients assessed, 57 were diagnosed with asthma and
      participated in the validation study. The total score did not significantly
      correlate with any of the objective measures of severity of asthma. However, the
      "Breathlessness" subscale score correlated weakly with PD20 methacholine.
      Internal consistency was high with Cronbach's alpha of 0.97 for the total score
      and 0.91-0.97 for the subscale scores. Test-retest reliability was also high for
      the total score and the subscale scores. The questionnaire detected a significant
      improvement in total quality of life score and "Breathlessness" and "Mood"
      subscale scores after a period of combined treatment with inhaled steroids and
      long acting bronchodilators. The German translation of the AQLQ-Sydney had a good
      internal consistency and test-retest-reliability in stable asthmatic patients. It
      shows responsiveness to treatment. Some correlations with objective markers were
      detected.

PMID- 16633953
TI  - Rather mild phenotype in a patient with homozygous null mutations in the alpha
      sarcoglycan gene.

PMID- 16633954
TI  - Coronary artery disease, nitric oxide and oxidative stress: the "Yin-Yang" effect
      -a Chinese concept for a worldwide pandemic.
AB  - Prevention of coronary artery disease (CAD) and reduction of its mortality and
      morbidity remains a major public health challenge throughout the "Western world".
      Recent evidence supports the concept that the impairment of endothelial function,
      a hallmark of insulin resistance states, is an upstream event in the
      pathophysiology of insulin resistance and its main corollaries: atherosclerosis
      and myocardial infarction. Atherosclerosis is currently thought to be the
      consequence of a subtle imbalance between pro- and anti-oxidants that produces
      favourable conditions for lesion progression towards acute thrombotic
      complications and clinical events. Over the last decade, a remarkable burst of
      evidence has accumulated, offering the new perspective that bioavailable nitric
      oxide (NO) plays a pivotal role throughout the CAD-spectrum, from its genesis to
      the outcome after acute events. Vascular NO is a critical modulator of coronary
      blood flow by inhibiting smooth muscle contraction and platelet aggregation. It
      also acts in angiogenesis and cytoprotection. Defective endothelial nitric oxide
      synthase (eNOS) driven NO synthesis causes development of major cardiovascular
      risk factors (insulin resistance, arterial hypertension and dyslipidaemia) in
      mice, and characterises CAD-prone insulin-resistant humans. On the other hand,
      stimulation of inducible nitric oxide synthase (iNOS) and NO overproduction
      causes metabolic insulin resistance and characterises atherosclerosis, heart
      failure and cardiogenic shock in humans, suggesting a "Yin-Yang" effect of NO in
      the cardiovascular homeostasis. Here, we will present a concise overview of the
      evidence for this novel concept, providing the conceptual framework for
      developing a potential therapeutic strategy to prevent and treat CAD.

PMID- 16633955
TI  - Long-term experience with oral or inhaled vasodilator combination therapy in
      patients with pulmonary hypertension.
AB  - BACKGROUND: Disease progression in pulmonary hypertension (PH) is common despite
      standard vasodilator monotherapy with iloprost, bosentan or sildenafil.
      OBJECTIVE: To investigate if the combination of these non-invasively applicable
      treatments is an effective option to address the multiple pathophysiological
      mechanisms present in PH. METHODS: We analysed the clinical course of 23 patients
      with PH, diagnosed as idiopathic (n = 15), chronic thromboembolic (n = 4), and
      associated with collagen vascular disease (n = 4), receiving combination
      vasodilator therapy at our institution. RESULTS: Vasodilator therapy before
      combination therapy consisted of inhaled iloprost (I; n = 12), or oral bosentan
      (B; n = 6) at a mean duration of 19 +/- 3 months. The combination therapy added
      was B (n = 8), sildenafil (S; n = 6) or I (n = 4) and in five patients,
      combination therapy was given from the beginning (3x BS, 1x IS, 1x IBS). Under
      combination therapy, the 6-minute walk distance (6MWD) increased significantly by
      46.7 +/- 24.8 m (p = 0.02) after three months, and after six months it was still
      38.3 +/- 28.3 m (p = 0.17) longer than before combination therapy. Respective
      changes in the Borg Scale and the NYHA functional class were -1.05 +/- 0.49 (p =
      0.014) and -0.42 +/- 0.19 (p = 0.02) after three months and -0.21 +/- 0.65 (p =
      0.61) and -0.38 +/- 0.29 (p = 0.26) after six months. Only minor side effects
      were reported. CONCLUSION: Combination vasodilator therapy in severe PH is safe
      and well tolerated. It significantly improves exercise capacity and stabilises
      the functional class in patients with severe PH deteriorating under single-agent
      therapy.

PMID- 16633956
TI  - Risk factors for developing metastatic infection from pyogenic liver abscesses.
AB  - OBJECTIVES: The aim of this study was to identify the risk factors for developing
      extra-hepatic metastases from pyogenic liver abscesses. METHODS: We conducted a
      retrospective study and reviewed 225 patients (age, 19-93 years) with a discharge
      diagnosis of pyogenic liver abscess from a large medical centre in Taiwan,
      between January 1995 and June 2000. Clinical data were collected from medical
      records. Of the 225 patients with a pyogenic liver abscess, 24 had extrahepatic
      metastases and were classified into the metastatic infection group; the remaining
      201 were classified into the non-metastatic infection group and served as the
      control group. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated by exact logistic regression. RESULTS: After adjustment for age, sex,
      and the duration of symptoms before admission, diabetes mellitus (adjusted OR,
      12; 95% CI, 3.3-67), alcoholism (adjusted OR, 5.2; 95% CI, 1.4-20), the time
      interval >7 days from the onset of symptoms to the time appropriate antibiotics
      were administered (adjusted OR, 3.9; 95% CI, 1.2-13), bacteraemia (adjusted OR,
      5.4; 95% CI, 1.4-30), and infection (adjusted OR, 5.0; 95% CI, 1.1-47) were
      associated with the development of extra-hepatic metastases from pyogenic liver
      abscesses. On the other hand, fever (adjusted OR, 0.28; 95% CI, 0.089-0.92) and
      right upper quadrant pain/tenderness (adjusted OR, 0.091; 95% CI, 0.0020-0.50)
      were associated with the non-metastatic abscesses. We performed a multivariate
      analysis and found that diabetes mellitus (multivariate OR, 7.7; 95% CI, 2.1-29)
      and alcoholism (multivariate OR, 8.9; 95% CI, 2.6-30) were the independent risk
      factors for developing metastatic infections; yet right upper quadrant
      pain/tenderness (multivariate OR, 0.11; 95% CI, 0.014-0.87) was the predictor of
      no metastatic abscesses. CONCLUSIONS: Our data suggest that diabetes mellitus and
      alcoholism are significant risk factors for developing metastatic infections from
      pyogenic liver abscesses. These findings seem to imply that underlying conditions
      of the host influence the development of extra-hepatic metastases from pyogenic
      liver abscesses.

PMID- 16633957
TI  - Contraceptive counselling and social representations: a qualitative study.
AB  - BACKGROUND: Contraceptive use is a complex issue and several studies have been
      conducted in an effort to understand user behaviour. It is of interest to explore
      the representations of professionals who give advice on contraception, since
      their views could have an impact on contraceptive use. METHODS: Individual in
      depth interviews of 65 healthcare professionals likely to provide contraceptive
      advice to patients at a Swiss maternity unit. RESULTS: 83% of healthcare
      professionals interviewed were favourable to contraception in general while being
      highly critical of its practical efficacy. The methods most often spontaneously
      cited were oral contraceptive pills, male condom, intrauterine devices and
      hormonal implants. Theoretically, all methods should be proposed during
      contraceptive counselling but in practice interviewees have different social
      representations of user groups and associate them with specific contraceptive
      methods. Personal experience appears to play a bigger role than scientific
      knowledge. CONCLUSIONS: The counsellor's social representations probably play an
      important role in determining user behaviour. These representations should be
      taken into consideration in the training of healthcare professionals in this
      field.

PMID- 16633958
TI  - The relationship between inflammation and the coagulation system.
AB  - Inflammation and coagulation play pivotal roles in host defence. As
      phylogenetically old responses, there is extensive cross-talk between
      inflammation and coagulation in enabling an adequate immune response against
      potentially injurious stimuli. Immune cells are important in the initiation of
      coagulation pathways, while various inflammatory mediators are capable of
      altering haemostasis. Vice versa, coagulation proteases have significant
      immunomodulatory effects. Understanding the mechanisms involved in the crosstalk
      between inflammation and coagulation may yield new therapeutic strategies for
      human diseases.

PMID- 16633959
TI  - Educational inequalities in life expectancy in German speaking part of
      Switzerland 1990-1997: Swiss National Cohort.
AB  - STUDY OBJECTIVE: Switzerland belongs to the group of nations with the highest
      life expectancy. However, it is unclear to what extent life expectancy varies
      across socio-economic groups. We used data from a large longitudinal study to
      quantify differentials in life expectancy across educational groups for men and
      women of different ages. DESIGN: The Swiss National Cohort linked the records
      from the December 4th, 1990 census with death certificate data up to 1997, using
      a probabilistic record linkage method. The current analysis was restricted to
      Swiss nationals resident in the German speaking part of the country. Life
      expectancy was calculated for four educational categories ("compulsory schooling
      or less", "vocational training", "upper secondary education", "university
      education") by constructing abridged life tables for men and women aged 30 or
      older. RESULTS: The study was based on 3.06 million persons and 262,552 deaths
      recorded during 19.01 million person-years of follow up. The educational level
      was lower in women than in men. In most age groups vocational training was the
      dominant educational category. At ages 30, 50, 65 and 80 men with university
      education lived 7.1, 5.4, 3.5 and 1.6 years longer than their counterparts with
      compulsory education or less. In women the corresponding differences were 3.6,
      3.1, 2.7 and 2.2 years. CONCLUSIONS: In Switzerland educational gradients in life
      expectancy are substantial, particularly among young and middle-aged men. Social
      policies and public health strategies should address this situation.

PMID- 16633960
TI  - Sleep and wakefulness disturbances in Swiss pharmacy customers.
AB  - BACKGROUND AND OBJECTIVE: Sleep disturbances are prevalent but often overlooked
      or underestimated. We suspected that sleep disorders might be particularly common
      among pharmacy customers, and that they could benefit from counselling.
      Therefore, we described the prevalence and severity of symptoms associated with
      sleep and wakefulness disorders among Swiss pharmacy customers, and estimated the
      need for counselling and treatment. METHODS: In 804 Swiss pharmacies (49% of all
      community pharmacies) clients were invited to complete the Stanford Sleep
      Disorders Questionnaire (SDQ), and the Epworth Sleepiness Scale (EPW). The SDQ
      was designed to classify symptoms of sleep and wakefulness into the four most
      prevalent disorders: sleep apnoea syndrome (SAS), insomnia in psychiatric
      disorders (PSY), periodic leg movement disorders/restless legs (RLS) and
      narcolepsy (NAR). Data were entered into an internet-linked database for analysis
      by an expert system as a basis for immediate counselling by the pharmacist.
      RESULTS: Of 4901 participants, 3238 (66.1%) were female, and 1663 (33.9%) were
      male. The mean age (SD) of females and males was 52.4 (18.05), and 55.1 (17.10)
      years, respectively. The percentages of female and male individuals above cut-off
      of SDQ subscales were 11.4% and 19.8% for sleep apnoea, 40.9% and 38.7% for
      psychiatric sleep disorders, 59.3% and 46.8% for restless legs, and 10.4% and
      9.4% for narcolepsy respectively. The prevalence of an Epworth Sleepiness Scale
      score >11 was 16.5% in females, and 23.9% in males. Reliability assessed by
      Cronbach's alpha was 0.65 to 0.78 for SDQ subscales, and for the Epworth score.
      CONCLUSIONS: Symptoms of sleep and wakefulness disorders among Swiss pharmacy
      customers were highly prevalent. The SDQ and the Epworth Sleepiness Scale score
      had a satisfactory reliability to be useful for identification of pharmacy
      customers who might benefit from information and counselling while visiting
      pharmacies. The internet-based system proved to be a helpful tool for the
      pharmacist when counselling his customers in terms of diagnostic classification
      and severity of symptoms associated with the sleeping and waking state.

PMID- 16633961
TI  - Diagnostic yield of flexible bronchoscopy in current clinical practice.
AB  - BACKGROUND: Flexible bronchoscopy is a procedure commonly performed for
      diagnostic and therapeutic purposes. The aim of this study was to assess the
      diagnostic yield and the safety of routine bronchoscopy techniques including
      transbronchial needle aspiration and transbronchial biopsy at a university
      hospital in Switzerland. METHODS: 616 consecutive bronchoscopies performed at the
      Pulmonary Medicine Department (University Hospital Basel) over a period of 6
      months were analysed retrospectively using bronchoscopy reports and hospital
      charts. Diagnostic procedures included bronchial washings, bronchoalveolar
      lavage, bronchial brushings, transbronchial needle aspiration and transbronchial
      biopsies. RESULTS: 430 bronchoscopies had a diagnostic, 186 a therapeutic
      indication. The overall diagnostic yield was 57% (245/430). Bronchoscopy
      performed for suspected tumours confirmed malignancy in 43% of cases.
      Bronchoscopy in suspected infection and tuberculosis identified pathogenic
      organisms in 46% and 27% of cases, respectively. The diagnostic yield for central
      and peripheral TBNA was 37.8 and 43.6%, respectively. Complications were very
      rare (n = 10, 1.6%) and were only minor. CONCLUSION: This study demonstrates that
      routine bronchoscopy techniques including transbronchial needle aspiration and
      transbronchial biopsy are safe and have a high diagnostic yield.

PMID- 16633962
TI  - Lack of cross-reactivity between cefotaxime and imipenem.

PMID- 16633963
TI  - Chronic pancreatitis: faces, facets, and facts.

PMID- 16633964
TI  - Diagnosis and management of chronic pancreatitis: current knowledge.
AB  - This paper reviews the current literature on chronic pancreatitis (CP). Despite
      marked progress in diagnostic tools, predominately imaging methods, no consensus
      has been reached on the nomenclature of CP, ie diagnosis, classification,
      staging, pathomechanisms of pain and its optimal treatment. A major problem is
      that no single reliable diagnostic test exists for early-stage CP except
      histopathology (rarely available). This stage is characterised typically by
      recurrent acute pancreatitis +/- necrosis (eg pseudocysts). Acute pancreatitis is
      a well-defined condition caused in 80% of cases by gallstones or alcohol abuse.
      Alcoholic pancreatitis, in contrast to biliary pancreatitis, progresses to CP in
      the majority of patients. However, a definite CP-diagnosis is often delayed
      because progressive dysfunction and/or calcification, the clinical markers of CP,
      develop on average 5 years from disease onset. The progression rate is variable
      and depends on several factors eg aetiology, smoking, continued alcohol abuse.
      Repeated function testing eg by the faecal elastase test, is the best alternative
      for histology to monitor progression (or non-progression) of suspected (probable)
      to definite CP. The pathomechanism of pain in CP is multifactorial and data from
      different series are hardly comparable mainly because insufficient data of the
      various variables ie diagnosis, classification, staging of CP, pain pattern and
      presumptive pain cause, are provided. Pain in CP is rarely intractable except in
      the presence of cancer, opiate addiction or extra-pancreatic pain causes. Local
      complications like pseudocysts or obstructive cholestasis are the most common
      causes of severe persistent pain which can be relieved promptly by an appropriate
      drainage procedure. Notably, partial to complete pain relief is a common feature
      in 50-80% of patients with late-stage CP irrespective of surgery and about 50% of
      CP-patients never need surgery (or endoscopic intervention). The spontaneous
      "burn-out" thesis of CP is in accordance with this observation although precise
      data of this phenomenon are scarce. Recent observations indicate that the
      progression to late-stage CP is markedly delayed in non-alcoholic compared to
      alcoholic CP. Therefore, spontaneous pain relief is also delayed but it occurs in
      close association with severe exocrine insufficiency suggesting that aetiology
      has a major impact on the duration of early-stage CP and that the "burn-out"
      thesis appears valid both in uncomplicated alcoholic and nonalcoholic late-stage
      CP. For treatment of steatorrhea and diabetes the reader is referred to recent
      reviews. Mortality and survival are closely related to aetiology with an
      increased death rate of about 50% within 20 years from onset in alcoholic CP
      compared to a markedly better prognosis in hereditary and idiopathic "juvenile"
      CP. The risk of pancreatic cancer is increased particularly in nonalcoholic CP
      based on the longer survival, whereas the risk of extra-pancreatic (smoking
      related) cancer is about 12-fold higher in alcoholic CP.

PMID- 16633965
TI  - Unexpected high prevalence of metabolic disorders and chronic disease among young
      male draftees--the Swiss Army XXI experience.
AB  - QUESTIONS: What are the benefits of laboratory screening examinations entailed in
      the new army recruitment concept (Swiss Army XXI)? PRINCIPLES/METHODS: Between
      January 1 and June 30, 2004, a total of 7714 of 11,322 (68%) draftees from 6
      Swiss army recruitment centres underwent clinical examination and laboratory
      testing. RESULTS: In 1.7% of the draftees we found elevated levels of the C
      reactive protein (CRP) as evidence of infection or inflammation. Although we
      found no case of acute hepatitis, 16 draftees had active hepatitis B and 1
      patient had active hepatitis C. Diseases, which were found by laboratory
      screening, and which forbid service in the army, included Crohn's disease,
      terminal renal insufficiency and essential thrombocytosis. In conditions such as
      anaemia (0.1%) or latent iron deficiency (7.2%), the cause may have to be
      elucidated before the start of military training. In other draftees (9.8%), we
      found elevated alanine-amino-transferase (ALAT) levels as a hint to possible
      alcohol abuse, which might impair the ability to serve in special units of the
      army. Finally, elevated levels of ferritin (0.1%), glucose (0.4%), and
      cholesterol (1.4%) may indicate iron overload/haemochromatosis, impaired glucose
      tolerance or even overt diabetes mellitus and hypercholesterolaemia. CONCLUSIONS:
      The results of our studies indicate that laboratory evaluation may confirm
      findings of the medical examination and may help to explain unspecific symptoms.
      Draftees with severe diseases and conditions caused by serious underlying disease
      can be excluded from military services early on the basis of laboratory testing.
      Future cost benefit analyses will have to show whether laboratory screening and
      consecutive early preventive measures are also advantageous to society as a whole
      and will reduce public health costs.

PMID- 16633966
TI  - Outcome of surgery for rectal cancer in octogenarians.
AB  - INTRODUCTION: The aim of this study was to assess the outcome of surgery for
      rectal cancer in patients 80 years of age or more. METHODS: A retrospective study
      of 29 patients older than 80 years, who presented in our institution between 1997
      and 2001 with the diagnosis of rectal adenocarcinoma, was undertaken. RESULTS:
      Median follow-up was 54 (range 27-78) months, and the median age of patients was
      85 (range 80-94) years. Twenty-four out of 29 patients (83%) underwent surgery,
      23 being operated electively. Twenty out of 24 patients (83%) underwent resection
      with curative intent, while four patients (17%) had a palliative procedure.
      Median hospital stay was 13 (range 10-35) days. Postoperative morbidity and
      mortality were 46% and 12.5%, respectively. However, when considering only
      elective procedures with curative intent, operative mortality was 5%. At the time
      of last follow-up, 13 patients were alive, five of them with no evidence of
      recurrent disease at 5 years, for an overall 2- and 5-year survival rate of 80%
      and 67%, respectively. Four out of the 7 deaths, which occurred after surgery,
      were due to medical causes unrelated to cancer. CONCLUSION: In our institution,
      two thirds of patients older than 80 years who presented with rectal cancer
      underwent surgery with curative intent. In this selected population, good results
      in terms of short-term survival can be achieved, at the price of an elevated
      postoperative morbidity. Whenever possible, treatment with curative intent should
      be considered in patients with rectal cancer, irrespective of the age.

PMID- 16633967
TI  - Becker muscular dystrophy with marked divergence between clinical and molecular
      genetic findings: case series.
AB  - Both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are
      caused by mutations of the X-linked dystrophin gene. BMD patients are less
      affected clinically than DMD patients. We present five patients with a diagnosis
      of BMD. First, two identical twins, with a deletion of exon 48 of the dystrophin
      gene, who experienced prominent muscle cramps from the age of three. The
      histopathological examination of muscle biopsies of these two twins revealed only
      very slight muscle fiber alterations. Second, two brothers who displayed marked,
      unusual intrafamilial variability of the clinical picture as well as showing a
      new point mutation in the dystrophin gene. And finally, a fifth boy who displayed
      a new point mutation in the dystrophin gene. Although he was clinically
      asymptomatic at the age of 15 and muscle biopsy only showed very minor myopathic
      signs, serum Creatine Kinase (CK) levels had been considerably elevated for
      years. Taken together, these cases add to the spectrum of marked discrepancies in
      clinical, histopathological and molecular genetic findings in BMD.

PMID- 16633968
TI  - HIV and solid organ transplantation: the Swiss experience.

PMID- 16633969
TI  - Sarcoidosis is a multisystem disorder with variable prognosis--information for
      treating physicians.
AB  - Sarcoidosis is a chronic granulomatous inflammatory disorder of unknown origin
      with heterogeneous outcome. In most cases the disease is self-limited, others
      progress or die from organ involvement, which is often associated with extensive
      scarring. Although often the primarily affected sites are the lungs and thoracic
      lymph nodes patients with sarcoidosis must be staged for multiorgan involvement.
      Modern treatment strategies appraise a critical awareness for the side-effect
      ratio of long-term medication. A main interest of research is to identify those
      patients with unfavourable outcome.

PMID- 16633970
TI  - Satisfaction of patients on chronic haemodialysis and peritoneal dialysis.
AB  - BACKGROUND: In contrast to quality of life, patient satisfaction on chronic
      haemodialysis (HD) and peritoneal dialysis (PD) has only rarely been studied.
      PATIENTS AND METHODS: All chronic HD and PD patients of the 19 centres located in
      western Switzerland were asked to complete a specific questionnaire, assessing
      dialysis centre characteristics, treatment modalities, and information received
      before and during dialysis treatment. Comparison between satisfaction with PD and
      HD was carried out on the patients in the nine centres offering both treatment
      modalities. RESULTS: Of the 558 questionnaires distributed to chronic HD
      patients, 455 were returned (response rate 82%). Fifty of 64 PD patients (78%)
      returned the questionnaire. The two groups were similar in age, gender, and
      duration of dialysis treatment. Completion rates were >90% for a majority of
      questions, with the lowest rate for information on sexuality (49% in HD and 54%
      in PD respectively). The lowest scores were recorded for information received
      about complications and costs of dialysis, and impact of end-stage kidney disease
      on sexuality. Satisfaction was lower in anonymous questionnaires. Satisfaction of
      PD patients was significantly better in 50% of the questions, particularly
      session tolerance (p<0.001), information about dialysis sessions (p=0.007), and
      complications (p=0.006). CONCLUSIONS: PD patients were on average more satisfied
      with their treatment than HD patients. Satisfaction could be improved with more
      information about potential adverse treatment effects.

PMID- 16633971
TI  - Unlicensed and off-label drug use in a Swiss paediatric university hospital.
AB  - BACKGROUND: Many medicines used in newborns, infants, children and adolescents
      are not licensed ("unlicensed") or are prescribed outside the terms of the
      marketing authorization ("off-label"). Several studies have shown that this is a
      common practice in various healthcare settings in the USA, Europe and Australia,
      but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study
      was to determine the proportion of unlicensed or off-label prescriptions in
      paediatric patients. METHODS: This pilot study was conducted prospectively over a
      six month period in the department of paediatrics of a university hospital.
      RESULTS: Sixty patients aged from three days to 14 years were included in the
      study. A total of 483 prescriptions were written for the patients. More than half
      of all prescriptions (247; 51%) followed the terms of the marketing
      authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients
      received at least one unlicensed or offlabel medicine. CONCLUSION: The use of
      unlicensed or off-label medicines to treat children was found to be common. Co
      operation between the pharmaceutical industry, national regulatory authorities,
      clinical researchers, healthcare professionals and parents is required in order
      to ensure that children do not remain "therapeutic orphans".

PMID- 16633972
TI  - ECG changes amongst patients with alcohol withdrawal seizures and delirium
      tremens.
AB  - INTRODUCTION: Alcohol withdrawal seizures and delirium tremens (DT) are serious
      complications of alcohol dependence. The prevalence of arrhythmias and other
      electrocardiographic (ECG) changes occurring in these clinical situations is not
      well studied. METHODS: We performed a retrospective analysis of clinical data and
      ECG's from patients discharged between 1995 and 2005 with the diagnosis of DT
      (ICD-Code F10.4) or alcohol withdrawal seizures (F10.3). Measurement of the ECG
      intervals was done in lead II. The corrected QT interval (QTc) was obtained using
      Bazett's formula. RESULTS: 49 patients (38 males; 11 females) with a mean age of
      48 years were included in the study. 23 patients with DT and 16 with convulsions
      were admitted to the hospitals. Ten patients developed DT while being
      hospitalised for other reasons. The QTc interval was prolonged (>440 ms and >460
      ms in males and females, respectively) in 31 patients (63%). Five patients (10%)
      developed tachyarrhythmias (two torsade de pointes, one sustained ventricular
      tachycardia, two supraventricular tachycardia, one atrial fibrillation). All
      returned to sinus rhythm after appropriate treatment. CONCLUSIONS:
      Tachyarrhythmias are common amongst patients with severe alcohol withdrawal
      syndromes. The majority of the patients had an acquired long QT syndrome which
      led to a torsade de pointes in two cases. No patient died in the hospital and all
      were discharged in sinus rhythm. Clinicians should possibly avoid QT prolonging
      drugs and carefully monitor the rhythm in patients with severe alcohol withdrawal
      syndromes.

PMID- 16633973
TI  - Watching football on TV may potentially be life-threatening.

PMID- 16633976
TI  - [Depression after stroke - diagnostic screening and algorithm].

PMID- 16633977
TI  - [Diagnostics and treatment of anorectic eating disorders].

PMID- 16633980
TI  - Androgen physiology.
AB  - Androgen receptors are present in numerous tissues throughout the female body,
      and knowledge of the specific actions of androgens at different sites is
      increasing, along with the understanding of their contribution to various
      pathophysiological states. This article reviews the physiology of androgens
      (testosterone and dihydrotestosterone) and immediate androgen precursors
      (dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEAS], and
      androstenedione), with specific reference to the androgen receptor, production
      and metabolism of C- (19) steroids, circulating androgen concentrations, and
      androgen actions. In addition, the evidence for physiological modulation of
      androgens including circadian variation, cyclical variation, age, and natural
      menopause is reviewed.

PMID- 16633981
TI  - Measurement of androgens in women.
AB  - Much of our knowledge about the physiologic role of androgens in women is based
      on measurements, primarily in serum, using radioimmunoassay (RIA) methodology
      that involves purification of the analyte by organic solvent extraction and
      column chromatography. Although the extraction/chromatographic RIA is highly
      reliable when properly validated, it is time consuming and costly. For this
      reason, direct RIA methods were developed. Subsequently, the radioactive marker
      was replaced by other labels that have been used in direct chemiluminescent,
      fluorescent, and enzyme immunoassays on autoanalyzers. Although direct
      immunoassays are simple and rapid, they are seldom thoroughly validated, and
      generally lack the sensitivity and specificity for reliable measurements of
      testosterone levels found in postmenopausal serum. In recent years there has been
      increased use of mass spectrometry assay methods to quantify steroid hormones.
      These methods are touted to become the gold standard for all steroid hormone
      measurements. Because urine contains predominantly glucuronidated androgens,
      multistep procedures are required for the measurement, which is not practical for
      diagnostic testing. Androgens also can be measured in saliva, but major
      methodologic problems are associated with the measurements. In addition, there is
      a misconception that salivary testosterone levels reflect free testosterone
      levels in serum.

PMID- 16633982
TI  - Clinical evaluation of women presenting with low libido and determination of
      whether androgen therapy might be appropriate.
AB  - The assessment of female sexual dysfunction (FSD) is often challenging in the
      clinical setting. Although androgen deficiency is regarded as a major cause for
      FSD, the causes of this condition are multifactorial. Women presenting with FSD
      require thorough clinical evaluation to determine the cause of FSD. Androgen
      therapy should be used in women only when clinical and biochemical parameters
      indicate that FSD stems from androgen deficiency. This review outlines the
      various causes of FSD, clinical and biochemical investigations required to
      diagnose androgen deficiency, and options for treatment of the woman found to
      have androgen deficiency as a cause of FSD.

PMID- 16633983
TI  - Dehydroepiandrosterone therapy as female androgen replacement.
AB  - Dehydroepiandrosterone (DHEA) is an abundant circulating androgen precursor
      preferentially produced by the adrenal glands. DHEA has been shown to exert its
      effects via downstream conversion to sex steroid hormones, neuromodulation,
      improvement in endothelial cell function, and possibly by acting on a cell
      membrane-bound receptor. Low levels of circulating DHEA have been demonstrated in
      women with diminished libido and other symptoms of sexual dysfunction. DHEA
      deficiency has also been associated with various drugs, and endocrine,
      nonhormonal, and age-related disorders. DHEA supplementation has been shown to
      produce beneficial effects in women with adrenal insufficiency. However, DHEA
      supplementation in healthy euadrenal subjects (including premenopausal and
      postmenopausal women with androgen insufficiency) is controversial; studies have
      yielded conflicting results regarding its beneficial effects on sexual function,
      metabolism, and overall well-being. Further research is needed to better
      elucidate the efficacy and safety of DHEA supplementation for the treatment of
      androgen insufficiency in women.

PMID- 16633984
TI  - Testosterone therapy in premenopausal women.
AB  - Testosterone therapy for postmenopausal women and women with surgical menopause,
      albeit controversial, is becoming more widespread. However, only limited data are
      available to support its use in premenopausal women. Androgens have important
      biological roles in young women, influencing bone and muscle mass, mood and well
      being, and libido. Pathophysiological states affecting ovarian and adrenal
      function or both may result in androgen deficiency in premenopausal women. Young
      women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy,
      premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal
      insufficiency, and hypopituitarism may have testosterone deficiency. Young women
      with loss of libido may also have testosterone deficiency. Medications that may
      lead to testosterone insufficiency include oral estrogen, oral contraceptives,
      and corticosteroids. Testosterone deficiency in young women may be underdiagnosed
      because the symptoms generally are nonspecific and the measurement of total and
      free testosterone is inaccurate with commonly used techniques. Only a few studies
      investigating the effects of testosterone therapy have been performed thus far in
      premenopausal women. Long-term trials evaluating safety and effectiveness of
      testosterone therapy in premenopausal women are lacking. Common adverse effects
      include hirsutism and acne, which reverse with discontinuation of treatment. The
      availability of testosterone regimens specifically designed for women is expected
      to help maintain testosterone levels within the normal range and clarify whether
      the apparent beneficial effects of testosterone therapy are physiological or
      pharmacological.

PMID- 16633985
TI  - Testosterone therapy for postmenopausal women: efficacy and safety.
AB  - The treatment of postmenopausal women with a variety of androgen formulations is
      increasing, despite the lack of clear guidelines regarding the diagnosis of
      androgen insufficiency. This review summarizes evidence on the efficacy and
      safety of adding testosterone to hormone therapy in postmenopausal women. Fair to
      good evidence exists that the use of testosterone in combination with hormone
      therapy has both benefits and risks. The benefits are an improvement in sexual
      function with various regimens of testosterone use (good evidence), an improved
      sense of well-being with transdermal testosterone (fair evidence), and a
      reduction in triglyceride levels with methyl testosterone (fair evidence). The
      most consistent risk is a reduction in high-density lipoprotein (HDL)
      cholesterol, particularly with methyl testosterone (good evidence). There has
      been insufficient reporting of other side effects; hence, testosterone therapy
      should be used with caution. The use of testosterone may be justified in specific
      clinical circumstances and should be limited to short-term use; long-term studies
      are not available. Close surveillance for HDL cholesterol and other side effects
      is necessary.

PMID- 16633986
TI  - [Renal failure and cardiovascular risk].
AB  - Prevalent studies concerning chronic renal failure (CRF) in the general adult
      population, using the Crockroft-Gault formula correcting serum creatinine values
      for calibration factors, indicate that about 22.8% have initial CRF. If the
      albuminuria itself is considered as an index of renal damage, we find a
      prevalence rate in the adult population of about 8.5%, with slight differences
      between females and males. Considering only this second more optimistic statistic
      and comparing it with the number of patients on dialysis, evidenced by the
      different specific registers, we observe that only 2% of the population with
      renal failure reach terminal uremia; and therefore, require substitutive therapy
      or renal transplantation. For many years, statistical analyzes have been carried
      out on the prevalence of pathologies present in patients who arrive at dialysis;
      to date, little has been done for patients with initial or average renal failure.
      Few of these studies are prospective. The data of studies concerning the elderly
      population suffering from CFR of varying degrees, as well as the data of
      longitudinal studies concerning patients controlled for a few years, have shown
      that cardiovascular diseases (CVD) are more responsible for the mortality of
      patients with even modest renal failure before reaching uremia compared to
      patients without renal failure. On the contrary, statistics on the prevalence of
      CVD in patients who arrive at dialysis are well-known, it can be >70%. Different
      organizations such as the National Kidney Foundation, the American Heart
      Association and the Seventh Joint National Committee on Prevention, Detection,
      Evaluation and Treatment of High Blood Pressure have considered the presence of
      CRF a cardiovascular risk factor.

PMID- 16633987
TI  - [Arterial hypertension and heart failure].
AB  - Systemic hypertension is a condition that frequently occurs before the onset of
      heart failure; furthermore, left ventricular hypertrophy (LVH) is an important
      risk factor for the development of heart failure (HF). Many studies have
      demonstrated that a linear relationship exists between increasing values of LV
      mass and the relative risk of the development of congestive HF. Hypertrophy
      hyperplasy of cardiomyocytes and endothelial cells leads to a reduction in
      coronary reserve and to cell death due to apoptosis or focal necrosis. This
      characteristic has been defined as 'load dependent myocyte dysfunction' and it is
      characterized both by structural dysfunctions with cell death and by functional
      alterations that are detectable early with the evaluation of myocardial function
      measuring the mid-wall shortening. The detection of extremely high myocardial
      growth is another factor that could help to make an early diagnosis of HF. The
      presence of 'load geometrical adaptation' markers, together with an early
      detection of systolic function anomalies that are often accompanied by diastolic
      modifications, could help to identify, in an early phase, patients who will
      develop symptomatic LV dysfunction; therefore, these patients can be intensively
      treated and undergo a specific follow-up.

PMID- 16633988
TI  - [Urinary albumin excretion and coronary artery disease].
AB  - The moderate elevation in urinary albumin excretion defined as microalbuminuria
      is common in the population and associated with cardiovascular (CV) risk factors.
      Microalbuminuria prevalence is low in the absence of CV risk factors and
      progressively increases with the number of the individual's CV risk factors. The
      main correlate of microalbuminuria is blood pressure (BP). The relationship
      between BP and microalbuminuria is continuous and graded since the prevalence of
      microalbuminuria increases with the severity of hypertension. Among hypertensives
      receiving treatment, BP control is associated with a low prevalence of
      microalbuminuria. Therefore, BP appears as a determinant of microalbuminuria
      rather than a mere correlate. For hypercholesterolemia, smoking and diabetes, the
      data are less strong, but point to an independent positive association with
      microalbuminuria. Altogether, data indicate that microalbuminuria in the
      population reflects the presence of CV risk factors. Data concerning
      microalbuminuria and coronary heart disease (CHD) support this idea. There is a
      continuous and graded relationship between urinary albumin excretion and CHD
      prevalence. High urinary albumin excretion is a likely sign of vascular damage
      existing both at renal and cardiac levels and induced by one or more uncontrolled
      CV risk factors.

PMID- 16633989
TI  - [Glomerulo-tubular balance in diabetes mellitus: molecular evidence and clinical
      consequences].
AB  - Diabetes mellitus is fast becoming a world epidemic. About one-third of
      individuals with diabetes, after 10 yrs, develop diabetic nephropathy, the first
      cause of end-stage kidney disease. The evolution of diabetic nephropathy can be
      considered in three stages: glomerular hyperfiltration, microalbuminuria (30-300
      mg/24 hr) and proteinuria (>300 mg/24 hr). This study was designed to investigate
      the tubular basis of glomerular hyperfiltration in early diabetes mellitus.
      Diabetes was inducted in rats with i.p. streptozotocin (65 mg/kg bw) for 6 days.
      At the end of the treatment, the glomerular filtration rate (GFR), measured by
      inulin clearance, had substantially increased in diabetic rats compared with
      controls. Quantitative polymerase chain reaction (PCR) and Western blot analysis
      reveal that in diabetic rats compared with controls, mRNA and protein abundance
      was higher for type 3 sodium/hydrogen exchanger (NHE3) in proximal tubule and
      ascending limbs of Henle's loop, and higher for bumetanide-sensitive sodium
      potassium-2 chloride cotransporter (NKCC2) in ascending limbs of Henle's loop.
      Western blot analysis confirmed the PCR results. Finally, the abundance of a 
      ENaC protein was unchanged in diabetic rats compared to controls. These results
      show that the primary sodium reabsorption increase in proximal tubule reduces
      salt concentrations at the macula densa. This elicits a tubuloglomerular feedback
      dependent increase in single nephron GFR.

PMID- 16633990
TI  - [Can cardiovascular calcifications be prevented in chronic kidney disease?].
AB  - Chronic kidney disease, with special regard to hemodialysis patients, develop
      frequent and widespread cardiac and vascular calcifications. In the heart
      calcifications are mainly located in the coronary arteries and in the valvular
      structures. There is a strict relation between cardiovascular mortality in CKD
      and the extent of cardiac and vascular calcifications. Therefore it is important
      to evaluate the causes of extraskeletal calcifications for the evaluation of the
      possibility of prevention. The importance of hyperphosphatemia, of hypercalcemia
      and of the increased CAxP product as a cause of cardiac calcification has been
      clearly underlined. However the mechanism of calcification, initially considered
      a physico-chemical precipitation, has been investigated with the conclusion that
      the process is mediated by cellular differentiation and production of factors
      favoring mineralization in the extracellular milieu. Increased serum phosphate
      levels are able to induce a transformation of vascular smooth muscle cells into
      osteoblast-like cells, able to produce factors known to be pro-mineralizing
      agents in the bone tissue. Further studies have revealed the importance of a
      number of inhibitors of calcification of cardiovascular structures, like Fetuin
      A, MGP, Osteopontin, Osteoprotegerin. Therefore at present the calcification
      process of vascular tissue is considered to be linked to a balance between
      inducers and inhibitors of calcium-phosphate deposits. Prevention of cardiac
      calcifications is at present mainly based of optimal control of serum phosphate
      and reduction of calcium load through the use of non-calcium containing phosphate
      binders. Treatment with statins for prevention and treatment of atherosclerosis
      is also an important means of decreasing the size and number of atherosclerotic
      plaques, where a portion of the calcification process develops.

PMID- 16633991
TI  - [Antihypertensive drugs in diabetic's hypertension].
AB  - Hypertension is defined by the Joint National Committee (JNC 7) as blood pressure
      (BP) > or =Y130/80 mmHg. It affects up to 70% of patients with type 2 diabetes
      and is twice as prevalent in diabetics as in non-diabetics. Due to its
      contribution to renal and cardiovascular disease, hypertension increases diabetic
      mortality four to five-fold. Therefore, a BP goal of 130/80 mmHg or less (125/75
      mmHg in patients with proteinuria >1 g/die and increased creatinemia), is
      recommended. For isolated systolic hypertension, defined as a systolic BP > or
      =Y180 mmHg with normal diastolic BP, the treatment goal is to reduce systolic BP
      to <160 mmHg. The evidence from most trials suggests that there are only minimal
      differences between the various antihypertensive drugs, and that almost all
      agents are capable of successfully reducing adverse clinical events.
      Nevertheless, there is evidence that certain drugs are more useful in preventing
      damage to a specific organ system; and therefore, the selection of the therapy
      should be guided by the presence of concomitant disease and the protection of the
      organ system that is most at risk. Beta-blockers and calcium channel blockers are
      effective antianginals; diuretics, angiotensin-converting enzyme (ACE) inhibitors
      and beta-blockers are useful for heart failure; ACE inhibitors and angiotensin
      receptor blockers are especially effective in preserving renal function. Adequate
      BP control, irrespective of the type of antihypertensive drugs used, should
      replace the academic debate on what is the best antihypertensive agent.

PMID- 16633992
TI  - [Natriuretic peptides in heart failure].
AB  - The recent discovery of cardiac endocrine function, together with the development
      of accurate and feasible assay methods for cardiac natriuretic hormone
      evaluation, i.e. for B-type natriuretic peptide (BNP) and inactive peptide NT
      proBNP have confirmed their pathophysiological and clinical significance for
      cardiovascular disease assessment. Concerning heart failure, their value is for
      diagnostic screening in selected/unselected populations, for differential
      diagnosis of dyspnea and for prognostic stratification, and as a guide for follow
      up and treatment of patients. Recent Italian recommendations pointed out that
      BNP/NT-proBNP has a role in ruling-out the diagnosis of heart failure in patients
      with dubious signs/symptoms: plasma BNP/NT-proBNP concentrations help in the
      clinical evaluation of chronic heart failure patients when risk stratification is
      needed, whereas the routine BNP/NT-proBNP assay is still not recommended to guide
      therapeutic decision-making.

PMID- 16633993
TI  - [Diastolic heart failure].
AB  - Until recently, the development of heart failure was related exclusively to the
      acute or chronic impairment in systolic function. Currently, the concept of heart
      failure not sustained primarily by a significant reduction in contractility has
      been clearly defined by several epidemiological and pathophysiological
      observations. This condition, defined as 'diastolic heart failure' or 'heart
      failure with preserved systolic function' can be related to different cardiac
      diseases with a higher prevalence in the elderly. Afterload mismatch situations,
      such as hypertension or aortic stenosis, as well as hypertrophic cardiomyopathy
      or pericardial diseases, determine this common clinical syndrome more frequently.
      Currently, the treatment of diastolic heart failure is still empirical, as there
      are few and inconclusive data coming from evidence-based medicine.

PMID- 16633994
TI  - [Use of diuretics in congestive heart failure: renal effects].
AB  - Diuretics are an integral part of the management of symptomatic heart failure.
      Although they have been used for several decades, there is still some ambiguity
      and confusion regarding the outcome and the optimal way of using these common
      agents. There are no large-scale randomized controlled trials that have evaluated
      the effect of diuretics on mortality and long-term morbidity in diastolic and
      systolic dysfunction. Nonetheless, in short-term studies furosemide has
      demonstrated to reduce symptomatic congestive heart failure and hospitalization,
      and to improve exercise capacity in the setting of systolic dysfunction. In this
      review, the classes, sites of action and renal effect of diuretics are reviewed
      and the various indications, optimal doses and recommendations on effective use
      and disuse are discussed. Namely, this review addresses the effects of emerging
      diuretic agents such as eplerenone--a selective mineral corticoid receptor
      antagonist, nesiritide--a brain natriuretic peptide-recombinant, and conivaptan-
      a vasopressin antagonist, in attempt to provide an update on current knowledge,
      even though adequate clinic data are not available for all agents.

PMID- 16633995
TI  - [Antioxidants, carnitine and erythropoietin].
AB  - Patients with renal disease possess an excess of cardiovascular (CV) risk
      factors, which predispose these patients to a high rate of morbidity and
      mortality due to CV disease. Oxidative stress and oxidative stress induced
      apoptosis play an important role not only in the pathophysiology and progression
      of renal disease, but also in the induction of myocardial damage and heart
      failure with important implications concerning CV morbidity and mortality in
      general, and particularly for patients with renal disease. This has stimulated
      the realization of studies aimed at evaluating therapies with antioxidants, given
      the evidence that patients with renal disease and heart failure have an imbalance
      towards pro-oxidant factors. The correction of anemia with erythropoetin (EPO) is
      another important aspect related to oxidative stress and apoptosis, which has
      also revealed positive effects for the improvement in heart failure. EPO cellular
      mechanisms are not completely known, and the identification of close biochemical
      and molecular relationships between EPO and heme oxygenase-1 (HO-1), which has
      potent antioxidant and anti-apoptotic properties, could provide the rationale for
      the beneficial effect of carnitine having been shown to possess antioxidant, anti
      apoptotic and erythropoietic activities and to induce HO-1 expression, not only
      in dialysis patients who fail to respond adequately to EPO, but also in patients
      with heart failure. The identification of these relationships between EPO, HO-1
      and carnitine and their biochemical mechanisms could contribute to the opening of
      new perspectives in the improvement of CV mortality in these patients, which
      remains the most important cause of death in patients with end-stage renal
      disease.

PMID- 16633996
TI  - [Beta-blockers in CHF: kidney's consequences].
AB  - In the 1980s congestive heart failure (CHF) was exclusively interpreted in
      hemodynamic terms. In accordance with this pathophysiologic hypothesis,
      cardiovascular drugs, mainly positive inotropics and/or vasodilators were used
      but not with significant results. From the mid 1980s, attention started focusing
      on the neurohumoral asset, strongly activated in patients suffering from CHF, and
      that it was itself the cause of CHF and responsible for the poor prognosis in
      these patients; therefore, to become the therapeutic target and to represent the
      rationale for using angiotensin-converting enzyme inhibitors (ACE-I), beta
      blockers and angiotensin II receptor blockers (ARBs). Evidence has been provided
      that these drugs can reduce morbidity and mortality. However, this evidence
      derives only from studies on the general population. In uremic patients, there
      are no dedicated controlled trials, assuming that the effect can be extended to
      these patients, but this is not necessarily true. The evidence based on
      retrospective analysis is a better survival in patients using ACE-I, but there
      are no prospective trials on mortality and morbidity available. Even less
      evidence is available on ARBs, in spite of their favorable pharmacokinetic
      characteristics. Uremia has been suggested as state of excess sympathetic
      activation; therefore, the benefit derived from beta-blockers should be even
      greater in uremic than in non-renal patients. Therapy with beta-blockers
      significantly reduces morbidity and mortality in the general population. These
      results are also specifically demonstrated in dialysis patients. Finally, only
      specifically designed trials will be able to answer the questions that
      cardiologists and nephrologists ask themselves in their daily practice.

PMID- 16633997
TI  - [Effects of aldosterone receptor blocker therapy on cardiac remodeling].
AB  - Cardiac remodeling is a physiologic or pathologic condition that occurs after
      myocardial infarction, pressure overload, myocardial inflammatory diseases,
      idiopathic dilated cardiomyopathy or volume overload. In spite of different
      etiologies, molecular, biochemical and mechanical processes are the same. The
      change in left ventricular function brings about a complex neuro-hormonal
      disorder, and disease progression is due to the combined action of several
      biological factors with toxic effects on the heart and vessels. The renin
      angiotensin-aldosterone system (RAAS) is very important in this process, through
      the effects on hydro-saline balance or through direct processes on myocardium. A
      direct effect of aldosterone in myocardial fibrosis after the detection of heart
      tissue aldosterone production has been demonstrated. In the past, the attention
      of physicians and researchers was focused on angiotensin II inhibition; and
      therefore, on angiotensin-converting enzyme (ACE) inhibitors, considering them
      sufficient to antagonize the effects of aldosterone. Nevertheless, this theory
      has been confuted in recent studies, with the evidence of elevated plasmatic
      aldosterone levels in patients treated with ACE-inhibitors and angiotensin
      receptor blockers. This phenomenon probably is due to the activation of secondary
      ACTH mediated pathways of trial aldosterone production. It has been demonstrated
      that aldosterone receptor inhibition is effective in reducing cardiac remodeling
      and mortality. AREA-IN CHF is the first multicentric, double blind, randomized,
      placebo control study to compare canrenone, an aldosterone receptor blocker, with
      placebo. The primary end point is the echocardiographic evaluation of left
      ventricular remodeling. Secondary end points are left ventricular end-systolic
      volume, ejection fraction, diastolic filling patterns, NYHA functional class, and
      mortality and hospitalizations of cardiac origin. In addition, bio-humoral
      effects of aldosterone receptor blocker therapy will be investigated. The study
      results will be available at the end of 2006.

PMID- 16633998
TI  - [Diabetic nephropathy: oral anti-diabetic agents or insulin?].
AB  - Diabetic nephropathy is a microvascular complication, as well as retinopathy and
      neuropathy of type 1 and type 2 diabetes mellitus. The pathogenesis directly
      correlates with hyperglycemia. The direct glucose toxicity, hypercoagulability,
      oxidative stress and endothelial dysfunctions play a role. Strict glycemic
      control with HbA1c levels <7% for 10 yrs is associated with a 25% microvascular
      end point reduction. Patients underwent pancreas transplantation, and after 10
      yrs the present nephropathy and functional and structural abnormalities have
      regressed. Diabetic nephropathy alters the pharmacokinetic profile of almost all
      oral anti-diabetic agents, as well as insulin metabolism; therefore, it is
      imperative to determine creatinine clearance. Renal failure requires insulin
      therapy. Incipient diabetic nephropathy allows very limited indications to oral
      anti-diabetic agents because of the altered pharmacokinetic profile and side
      effects (hypoglycemia with secretagogues agents, lactic-acidosis with metformin
      and other biguanides, and hydric retention and weight gain with
      thiazolidinediones). Moreover, oral anti-diabetic agents reduce the percentage of
      HbA1c by no more than 1.5%. Insulin therapy is preferred, with a dose reduction
      when creatinine clearance is <60 mL/m. To control better the post-prandial
      glycemic peak, it is useful to use bolus insulin analogues at each meal and basal
      intermediate-acting insulin at bedtime to mimic the natural insulin patterns as
      far as possible.

PMID- 16633999
TI  - [Nutrition in diabetic nephropathy].
AB  - The incidence of end-stage renal failure has increased in Italy from 70-80 to 120
      per 1x10(6). About 20-30% of patients with diabetes develop nephropathy, usually
      within 20-25 yrs after disease onset. Diet plays an essential role in the therapy
      of diabetic nephropathy. A well planned diabetic diet with intensive glycemic
      control can significantly reduce the risk of microalbuminuria development, and
      moderate protein restriction reduces hyperfiltration and intraglomerular
      pressure, and retards the progression of diabetic glomerulopathy. Various studies
      have shown a positive effect of diet with a protein intake of approximately 0.8
      g/kg(-1)/day(-1) in patients with overt nephropathy, with a further restriction
      to 0.6 g/kg(-1)/day(-1) when the glomerular filtration rate begins to fall. Extra
      protein intake should counterbalance massive proteinuric losses.

PMID- 16634000
TI  - [Sustained low-efficiency dialysis (SLED) in patients with prevalent systolic
      heart failure refractory to medical treatment and with chronic renal failure].
AB  - Systolic heart failure refractory to conventional medical therapy is the
      principal cause of the high hospitalization rates and of high mortality risks.
      When this condition is associated with chronic renal failure it is necessary to
      treat the body liquid composition alterations, and the alterations in the
      hemodynamic state without creating low flow conditions, trying to achieve an
      electrolytic and an acid-base balance to reduce the plasmatic volume and permit
      refilling between the interstitium and plasm. Sustained low-efficiency dialysis
      (SLED) is a dialysis technique allowing the maintenance of hemodynamic stability
      through a reduced ultrafiltration rate, it allows an adequate clearance of small
      solutes, and with sustained treatment it maximizes the dialysis dose and
      determines a clinical improvement through the removal of the hydric overload. Our
      experience suggests that SLED is a substitutive treatment for acute dialysis in
      patients with systolic heart failure refractory to conventional medical
      treatment.

PMID- 16634001
TI  - [Diuretic therapy in heart failure].
AB  - Diuretic therapy is a drug therapy that increases urine volume, but not
      glomerular filtration rate (GFR). The diuretics act predominantly on tubular
      sites; the drugs that increase GRF are the aminophyllines, the positive inotropy
      or vasoactive substances that increase afferent arteriolar flux or
      intraglomerular pressure. We can divide the diuretics into six categories: 1)
      carbonic anhydrase inhibitors: acetazolamide, dichlorphenamide, methazolamide; 2)
      osmotic diuretics: glycerol, mannitol, urea; 3) loop diuretics: furosemide,
      bumetanide, ethacrynic acid, piretanide, torsemide; 4) thiazide and thiazide-like
      diuretics: chlorothiazide, trichlormethiazide, indapamide, chlorthalidone,
      metolazone; 5) potassium-sparers: a) kidney epithelial sodium channel inhibitors:
      amiloride and triamterene; b) aldosterone receptor antagonists: spironolactone,
      canrenoate potassium, eplerenone; 6) ADH antagonists: lithium salts,
      demeclocycline and ethanol. Diuretic therapy is useful in treating acute and
      chronic renal insufficiency, congestive heart failure, cirrhosis, overhydration
      and hypertension. Diuretic therapy increases urine volume, ion loss (except Na+,
      K+), and modifies diffusion (dilute urine) and convection mechanisms (reduced
      tubular absorption). Therefore, diuretics are very useful non-dangerous drugs.

PMID- 16634002
TI  - [Quality of life in patients with combined treatments for heart failure].
AB  - The low quality of life in patients with end-stage heart failure is correlated,
      above all, to frequent hospitalization and to the awareness of having an illness
      that limits survival. The quality of life in these patients with heart failure
      using treatment with sustained low efficiency dialysis (SLED) is determined
      through the Minnesota Living with Heart Failure (MLHF) Questionnaire. The
      reliability of this evaluation system has been examined through consultation with
      international trials. After 1 yr of this treatment, we observed an improvement in
      quality of life.

PMID- 16634003
TI  - [Promoting clinical research].
AB  - Although the development of science as any human activity is basic and practical
      at the same time, clinical science did not develop with the same pace of basic
      science. There is a need to support clinical science by granting independence, by
      enrolling young physician scientists, by giving them appropriate mentoring and
      economic support.

PMID- 16634004
TI  - Impact of correlation between pesticide parameters on estimates of environmental
      exposure.
AB  - Monte Carlo techniques are increasingly used in pesticide exposure modelling to
      evaluate the uncertainty in predictions arising from uncertainty in input
      parameters and to estimate the confidence that should be assigned to modelling
      results. The approach typically involves running a deterministic model repeatedly
      for a large number of input values sampled from statistical distributions. A key
      decision in setting up a probabilistic analysis is whether there is correlation
      between any of the inputs to the analysis. Pesticide properties are often the
      most sensitive in exposure assessment. Analysis of the literature demonstrated
      that there are examples of both positive and negative correlation between the
      sorption and degradation behaviour of a pesticide, but that general trends are
      not apparent at present. The inclusion of even weak correlation between sorption
      and degradation was found to greatly influence a probabilistic analysis of
      leaching through soil. Correlation will reduce the predicted extent of leaching
      for pesticides, and it is recommended to set the correlation to zero unless the
      experimental data support an alternative assumption (i.e. where the correlation
      is statistically significant (P <or= 0.05) and experimental artefacts can be
      excluded).

PMID- 16634006
TI  - Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency
      syndrome patients: protease inhibitor-mediated neurotoxicity.
AB  - OBJECTIVE: Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) is
      a common and disabling disorder, often associated with antiretroviral therapy
      (ART) use. We investigated the clinical features and associated pathogenic
      determinants of HIV-SN in a neurological cohort of HIV-infected patients,
      together with a novel model of HIV-SN. METHODS: HIV-infected patients with
      neurological disease were investigated in terms of clinical and laboratory
      aspects together with ART exposure focusing on symptomatic HIV-SN. Rat-derived
      dorsal root ganglion (DRG) cultures, transgenic for human CD4 and CCR5 treated
      with ARTs or HIV infected, or both, were studied with respect to quantitative
      neuronal injury. RESULTS: Among 221 patients assessed from 1998 to 2004, 120 had
      no sensory neuropathy, whereas 101 displayed HIV-SN, including 64 with distal
      sensory neuropathy and 37 with antiretroviral toxic neuropathy. HIV-SN patients
      exhibited significantly greater mean age, peak plasma viral loads, and exposure
      to neurotoxic dideoxynucleosides and protease inhibitors, including indinavir,
      saquinavir, or ritonavir. HIV-infected DRG cultures exposed to indinavir or
      didanosine showed significant neuronal atrophy, neurite retraction, and process
      loss, compared with controls. Indinavir was selectively cytotoxic to DRG
      macrophages compared with other ARTs. INTERPRETATION: Protease inhibitor exposure
      is an unrecognized risk factor for the development of HIV-SN, which may
      potentiate neuronal damage in HIV-infected DRGs, possibly through the loss of
      macrophage-derived trophic factors.

PMID- 16634007
TI  - Natalizumab: immune effects and implications for therapy.

PMID- 16634008
TI  - The relation between intracranial and intraocular pressures: study of 50
      patients.
AB  - OBJECTIVE: We evaluated the correlation between intracranial (ICP) and
      intraocular pressure (IOP). METHODS: Of the 77 patients who underwent a lumbar
      puncture, 27 were excluded secondary to a history of glaucoma, using drugs
      effective on IOP, and abnormal funduscopic examination. ICP was measured by
      lumbar puncture. IOP was measured by two scales of Schiotz tonometer in both
      eyes, and the mean was calculated. RESULTS: We found a significant correlation
      between ICP and mean IOP (p < 0.001; r = 0.955). Body mass index, age, and
      disease type had no significant effect on this correlation. INTERPRETATION: IOP
      is correlated with ICP.

PMID- 16634009
TI  - Reply: To PMID 11456302.

PMID- 16634010
TI  - Exercise and myotonic dystrophy: a 31P magnetic resonance spectroscopy and
      magnetic resonance imaging case study.

PMID- 16634011
TI  - Low-grade central nervous system lymphoma: clarity through a hazy lens.

PMID- 16634012
TI  - Nerve center: Events, people, and issues in academic neurology.

PMID- 16634013
TI  - Dopamine dysregulation syndrome in Parkinson's disease patients: from reward to
      penalty.

PMID- 16634015
TI  - Weaning practices of the Makushi of Guyana and their relationship to infant and
      child mortality: a preliminary assessment of international recommendations.
AB  - The World Health Organization (WHO) recommends exclusive breastfeeding (EBF) for
      the first 6 months of life, primarily because of potential immunological benefits
      which are deemed to outweigh nutritive costs for infants. This recommendation is
      controversial, as studies of the relationship between the term of EBF and infant
      and child health have produced conflicting results. The purpose of this paper is
      to evaluate the relationship between the term of EBF and infant and child
      mortality among a group of swidden-horticulturalists in lowland South America.
      Consistent with the WHO, we hypothesized that EBF <6 months will compromise the
      survival of the infant or child. This relationship was assessed via recall data
      generated in 2001 in structured interviews with 60 Makushi Amerindian women in
      Guyana's North Rupununi region. The data were analyzed with t-tests, Fisher's
      exact test, and logistic regression. The results do not support our hypothesis;
      the term of EBF is not found to be related to infant or child mortality. This is
      surprising given the potential for contamination in nonbreast-milk foods in this
      environment. Notably, this is occurring among mothers who are not energetically
      stressed. We propose that the apparent lack of benefit of EBF >or=6 months is due
      to insufficient energy supply from breast milk alone, which may predispose the
      child to morbidity when subsequently stressed. This study concurs with others
      which revealed no significant benefits to the infant of EBF >6 months, and the
      recognition that universal recommendations must be situated within local
      ecological contexts.

PMID- 16634016
TI  - Relationship of single measures of cardiorespiratory fitness and obesity in young
      schoolchildren.
AB  - The purpose of this study was to examine differences of cardiorespiratory fitness
      (CRF) among weight groups, and the associations of CRF with obesity (body mass
      index) in a sample of young children. Anthropometric data (height, body mass, and
      two skinfolds) were collected for 255 healthy children aged 8-10 years (127 boys
      and 128 girls). Children were placed in three groups (nonobese, overweight, and
      obese), using body mass index (BMI) sex- and age-specific cutoff points.
      Cardiorespiratory fitness was assessed with a 1-mile run test. Participants were
      separated into two groups: fit and unfit, according to age- and sex-specific
      scores defined by FITNESSGRAM. The prevalence of overweight (30.5% vs. 29.1%) and
      obesity (13.2% vs. 12.6%) was at the same magnitude for boys and girls. Overall,
      109 children (42.7%) were overweight and obese. Sums of skinfolds, weight, and
      BMI were significantly lower (P < 0.05) in lean boys and girls compared to their
      overweight and obese counterparts. Regarding height, no significant differences
      were found in girls, while in boys, significant differences were only found
      between nonobese and obese. No differences were found in obesity groups according
      to CRF in boys, while significant differences were found for girls (P < 0.01).
      Logistic regression analysis showed that girls who were overweight (odds ratio =
      0.05, P = 0.000) or obese (odds ratio = 0.09, P = 0.001) were likely to be unfit.
      No significant results were found in boys. Overweight and obese children
      presented higher sums of skinfolds and weight compared with their lean
      counterparts. Increased BMI was significantly associated with lower CRF in girls.
      Thus, our data clearly showed potential gender differences of body composition in
      CRF, which would be of great clinical significance. Therefore, even at young
      ages, at least for girls, the beneficial impact of low BMI values on CRF is shown
      with important clinical and public health implications.

PMID- 16634017
TI  - Food insecurity in rural Tanzania is associated with maternal anxiety and
      depression.
AB  - Food insecurity is a major health problem that has pervasive effects on many
      human biological outcomes. In particular, there are compelling theoretical and
      empirical reasons to expect that the relationship between food insecurity may be
      directly related to mental health morbidities, and may be quantifiable in
      developing country settings. This preliminary study examined whether caretaker
      reports of food insecurity were associated with anxiety and depression among four
      ethnic groups in two communities of rural Tanzania. In-home interviews were
      conducted in June-August of 2005 among female caretakers (n = 449). In addition
      to collecting household and demographic data, modified versions of the USDA's
      food security module and Hopkins Symptom Checklist (HSCL) were used to measure
      food insecurity and anxiety and depression. Consistent with predictions, the
      results showed a strong positive correlation between a caretaker's score on the
      food insecurity instrument and her summed response on the HSCL (P < 0.0001). This
      association was maintained in all four ethnic groups, even when controlling for
      individual-level covariates such as caretaker's age and marital status. Issues of
      causality and hypotheses that might explain this robust finding are discussed, as
      are methodological and theoretical implications.

PMID- 16634018
TI  - Mode of inheritance of dermatoglyphic pattern intensity index on fingers in five
      Indian populations: a comparative study between individual trait and its factor.
AB  - Our previous study (Karmakar et al. 2005 Ann. Hum. Biol. 32:445-468) was on 500
      pedigrees of five different populations, with factor 1 comprising quantitative
      finger dermatoglyphics (including pattern intensity index, PII) and factor 1
      controlled by major genes. The present results of a complex segregation analysis
      of the individual trait PII of the same five populations were compared with
      previous results to ascertain the extent of variation between individual trait
      PII and its factor (factor 1) with respect to mode of inheritance. The
      comparative findings are very similar in five populations, irrespective of
      different ethnic groups. This result suggests that the variability of their
      biological relevance is influenced by the same genetic component, thus
      representing a similar mode of inheritance with major gene involvement in all
      populations.

PMID- 16634019
TI  - Daughters increase longevity of fathers, but daughters and sons equally reduce
      longevity of mothers.
AB  - Reproduction is energetically and physiologically expensive, and an individual
      investing resources into producing offspring should suffer costs such as
      deterioration in health condition and possibly shorter life span. Since the
      energetic and nutritional demands of pregnancy and breastfeeding render
      reproductive costs much higher in women than in men, women with a large number of
      children should show signs of deterioration in condition, while men with large
      families should not. However, whether reproductive costs reduce longevity in
      women is still questionable, and in men this issue has not been adequately
      addressed. In addition, since sons are energetically more expensive to produce
      than daughters, having sons should have a more pronounced negative impact on
      maternal longevity than having daughters. Here we document a striking disparity
      in the impact of children on the life span of mothers and fathers in a Polish
      rural population. We show for the first time that number of daughters was
      positively related to a longer life span of their fathers, increasing their
      longevity on average by 74 weeks per daughter born, while number of sons did not
      have a significant effect on paternal longevity. In contrast, in women, the
      number of daughters and number of sons reduced maternal longevity and did so to
      the same extent, on average by 95 weeks per son or daughter, indicating that for
      women, the costs of having sons and daughters are similar.

PMID- 16634020
TI  - School fitness tests as predictors of adult health-related fitness.
AB  - Relationships between adolescent physical fitness and adult health-related
      fitness were investigated. Forty-five subjects (20 males, 25 females)
      participated in physical fitness tests in 1976 and again in 2001. The adolescent
      physical fitness tests were distance running (2,000 m for boys or 1,500 m for
      girls), 50 m run, pull-ups (boys) or flexed arm hangs (girls), shuttle run, a 30
      sec sit-up test, standing broad jump, hand grip-test, and sit-and-reach test. The
      adult health-related physical fitness index (APFI), stratified by sex, was formed
      by summing the z-scores of a bicycle ergometer test, sit-up test, hand-grip test,
      and sit-and-reach test. Height- and weight-adjusted correlations between
      adolescence and adulthood for exactly similar tests for men and women were,
      respectively, 0.74 (95% CI, 0.44-0.89) and 0.53 (95% CI, 0.17-0.76) in sit-and
      reach tests, 0.41 (95% CI, -0.04 to 0.72) and 0.55 (95% CI, 0.20-0.78) in sit-up
      tests, and 0.53 (95% CI, 0.11-0.44) and 0.44 (95% CI, 0.05-0.71) in hand-grip
      tests. When all adolescent tests were put in regression analysis together with
      BMI in 2001, the significant explanatory factors for APFI were distance running
      ability and the sit-and-reach test for men and sit-up test, flexed arm hang, and
      BMI in 2001 for women.

PMID- 16634021
TI  - Indices of body composition and chronic morbidity: a cross-sectional study of a
      rural population in central Russia.
AB  - Our objective was to clarify how different groups of chronic morbidities are
      associated with indices of body composition, such as body mass index (BMI), waist
      circumference (WC), waist to hip ratio (WHR), skinfold index (SF), and fat-free
      mass index (FFMI). Our sample comprised Chuvasha residing in numerous villages in
      a rural area of the Russian Federation. The investigated cohort included 787
      males aged 18-89 years, and 716 females aged 18-90 years. We performed a cross
      sectional, community-based study of a large sample of individuals not receiving
      any medications for treatment or prevention of chronic morbidities. To elucidate
      the association between morbidity and age-adjusted anthropometrical indices, we
      used one-way analysis of variance, wherein the above indices were the dependent
      variables, while individuals affected vs. nonaffected for a specific disease were
      the grouping variables. Individuals with ischemic heart disease, diabetes
      mellitus, hypertension, and peptic ulcer showed significant differences in their
      BMI, WC, WHR, and SF. In the first diseases, mean values of anthropometric
      indices were higher in affected individuals, whereas in the peptic ulcer group,
      mean values were higher in the nonaffected. Skin diseases and gynecological
      diseases showed significant differences in WHR. Mean values in affected
      individuals were lower than in the nonaffected. The group afflicted with local
      forms of arthritis showed significant differences in FFMI, suggesting that
      arthritis is not linked to obesity, but is linked to high lean mass. Rheumatic
      diseases positively correlated with WC and FFMI.

PMID- 16634022
TI  - Polymorphisms in the vitamin D receptor and their associations with risk of
      schizophrenia and selected anthropometric measures.
AB  - The association between vitamin D levels and skeletal growth has long been
      recognized. However, exposure to low levels of vitamin D during early life is
      also known to alter brain development, and is a candidate risk factor for
      schizophrenia. This study examines the association between four polymorphisms in
      the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three
      anthropometric variables (height, head size, and head shape). Four single
      nucleotide polymorphisms (SNPs; rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI,
      and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with
      schizophrenia and 189 healthy controls. No significant associations were detected
      between any of the four VDR SNPs and risk of schizophrenia. Patients were
      slightly but significantly shorter compared to controls. Of the four SNPs, only
      rs10735810/FokI was associated with any of the anthropometric measures: the M4
      isoform of this SNP was significantly associated with larger head size (P =
      0.002). In light of the evidence demonstrating a role for vitamin D during brain
      development, the association between polymorphisms in VDR and brain development
      warrants closer scrutiny.

PMID- 16634023
TI  - Anger expression and lifestyle incongruity interactions on blood pressure in
      Samoan adults.
AB  - Prior research on psychosocial stress and blood pressure (BP) in adult Samoans
      identified the separate influences of lifestyle incongruity and anger expression
      within the context of societal modernization. The objective of this cross
      sectional study was to determine the interactions between lifestyle incongruity
      and anger expression on BP in 376 men and women 25-65 years of age from Samoa.
      Participants were randomly selected from nine villages. Body mass index (BMI) and
      BP were measured by standard techniques. Anger expression was measured with an
      adapted version of the Spielberger Inventory. Material lifestyle was assessed by
      inventory of household items, exposure to news media, and off-island travel.
      Occupation and education lifestyle incongruities were calculated by subtracting
      the standardized lifestyle scale from the standardized occupation and education
      scales, respectively. Two-factor analysis of variance models with interactions
      were estimated within specific subgroups, with age- and BMI-adjusted BP as
      outcomes. In women <40 years of age with a material lifestyle relatively lower
      than their educational rank, anger suppression is associated with higher adjusted
      systolic BP. In young men whose material lifestyle is relatively lower than their
      occupational rank, those who report frequent experiences of Samoan culture
      specific anger feelings have higher adjusted diastolic BP. We hypothesize that
      among young women, the higher BP may be due to stress arising from both a
      normative proscription against emotional expression, and a mismatch between their
      relatively higher educational level and lower material lifestyle. For young men,
      higher BP levels may be attributed to expected donations of earnings to the
      extended family that exceed their own material lifestyle, in combination with
      more frequent Samoan-specific feelings of anger.

PMID- 16634024
TI  - Biological aging and Cox hazard analysis of mortality trends in a Mennonite
      community from south-central Kansas.
AB  - This study investigated mortality in 568 individuals from the Goessel Mennonite
      community in rural central Kansas. There were three main objectives to this
      research: 1) characterize mortality trends within a biologically well-defined
      Mennonite community; 2) determine what biochemical, morphological, and
      physiological risk factors could be related to all-cause mortality, stratified by
      age and sex; and 3) compare these results to previously described variables that
      were associated with both biological age and mortality in this population.
      Mortality data were obtained from three sources: Kansas Vital Records, the Social
      Security death index, and church records. In total, 221 (39%) individuals were
      found to have died in this population between January 1980-June 2002. Analogous
      to the larger US population, the three leading causes of death in this community
      were heart disease, cancer, and stroke, accounting for 60% of all deaths. Besides
      advancing age, the greatest biological risk factor in this population was
      decreased amounts of albumin in men (relative risk, 2.47), potentially indicating
      underreported cases of either chronic kidney disease or frailty syndrome for
      males. Cox proportional hazard models demonstrated that increased amounts of
      total cholesterol may provide a protective effect for elderly individuals. We
      conclude, based on the previously described heritability of both albumin (h(2) =
      0.40) and total cholesterol (h(2) = 0.50) in this population, that underlying
      genetic factors associated with both chronic degenerative diseases and biological
      aging may have important implications for understanding mortality patterns in
      this community.

PMID- 16634025
TI  - Attention-deficit hyperactivity disorder and fluctuating asymmetry in another
      college sample.
AB  - Attention deficit/hyperactivity disorder (AD/HD) represents a developmental lag
      that may be reflected in fluctuating asymmetry (FA), i.e., differences from
      perfect symmetry in traits that display bilateral symmetry. Burton et al. (2003
      Am. J. Hum. Biol. 15:601-619) found a statistical trend for FA to increase (as
      dermatoglyphic index or as total index) as the behavioral measure for AD/HDness
      (Rasch logit values derived from the Wender Utah Rating Scale, or WURS) increased
      in males but not in females. The objective here was to do a similar study in an
      independently collected sample of college students (n = 222; 61 male, 161 female)
      not selected for AD/HD, looking at FA vs. symptoms for AD/HD based on Rasch
      versions of responses to the Diagnostic and Statistical Manual of Mental
      Disorders (DSM IV) (Barkley and Murphy 1998 Attention-Deficit Hyperactivity
      Disorder, New York: Guilford Press, p. 95-96) and the more comparable shortened
      WURS. FAs were lowest for body and ear height, and highest for eye width and nose
      width, and ranged from 0.01 +/- 0.001 (mean +/- SE) for foot and ankle widths to
      0.13 +/- 0.01 in eye and nose widths for both sexes; the sexes did not differ
      significantly. Males displayed higher AD/HD symptom rates overall. There was a
      significant correlation between body FA and the WURS measure in females after
      Bonferroni correction (P = 0.002, r(2) = 0.058). Thus, AD/HD symptoms levels
      increased with an increase in body FA in female college students not selected for
      AD/HD.

PMID- 16634026
TI  - Validity and normative data for thirty-second chair stand test in elderly
      community-dwelling Hong Kong Chinese.
AB  - It is important to establish valid field measures of lower body strength in the
      elderly, and to provide representative normative values that are culturally
      specific in order to help health professionals in the risk assessment of this
      group. A sample of 1,038 elderly Hong Kong Chinese undertook a 30-sec chair stand
      test (30CST), with a subsample of 143 completing isometric measures of maximal
      hip flexion and knee extension, plus a habitual physical activity questionnaire.
      The 30CST was significantly, yet only weakly, correlated with the isometric
      strength measures (r approximately 0.3-0.4), but accurately discriminated between
      levels of habitual physical activity and across ages in decades. The normative
      values generated provide useful data for health screening in this elderly Hong
      Kong population, but do not compare well with their healthier US counterparts.

PMID- 16634027
TI  - Growth rates and life histories in twenty-two small-scale societies.
AB  - This study investigates variation in body growth (cross-sectional height and
      weight velocity) among a sample of 22 small-scale societies. Considerable
      variation in growth exists among hunter-gatherers that overlaps heavily with
      growth trajectories present in groups focusing more on horticulture. Intergroup
      variation tends to track environmental conditions, with societies under more
      favorable conditions displaying faster growth and earlier puberty. In addition,
      faster/earlier development in females is correlated with higher mortality. For
      example, African "Pygmies," Philippine "Negritos," and the Hiwi of Venezuela are
      characterized by relatively fast child-juvenile growth for their adult body size
      (used as a proxy for energetic availability). In these societies, subadult
      survival is low, and puberty, menarche, and first reproduction are relatively
      early (given their adult body size), suggesting selective pressure for
      accelerated development in the face of higher mortality. In sum, the origin and
      maintenance of different human ontogenies may require explanations invoking both
      environmental constraints and selective pressures.

PMID- 16634028
TI  - Preference for sons and sex ratio in two non-Western societies.
AB  - Moroccan Berbers and the Bolivian Aymara are two unrelated peasant groups living
      in adverse environments with a still rather traditional agriculture. Precarious
      life conditions may be responsible for the importance given to male labor and
      hence for the cultural preference conferred on male descent. This preference,
      expressed in the social valorization of sons to the detriment of daughters, is
      more emphasized if the socioeconomic status of the family is lower. Interpreted
      according to the cost/benefit approach of Fisher (1958 Genetical Theory of
      Natural Selection, New York: Dover) of variations in the sex ratio and to its
      later developments (Trivers and Willard 1973 Science 179:90-91; Trivers 1985
      Social Evolution, Menlo Park: Benjamin/Cummings; Hewlett 1991 J. Anthropol. Res.
      47:1-37; Smith 1993 Ethol. Sociobiol. 14:39-44), these cultural characteristics
      could determine that parents bias the care allocated to their progeny in favor of
      sons, to the detriment of daughters. This could eventually affect their
      respective survival and finally modify the offspring tertiary sex ratio. This
      study compares differences in survival as indicators of parental care according
      to a child's sex and across three economic strata: poor, medium, and high. The
      Moroccan data express no other sex differences in survival than an advantage for
      daughters during the preweaning period in the medium and high strata. Within the
      same sex and across economic strata, a greater mortality between age 10-20 years
      is observed for boys of the poorest stratum. The Aymara data do not show sex
      differences by economic stratum, except for an advantage to daughters between
      birth and 5 years in the medium group, and no survival differences within the
      same sex across economic strata. These results suggest either that despite the
      social valorization of male progeny no differences in parental care according to
      sex occur, or that their magnitude is not great enough to contrast the survival
      of sons and daughters.

PMID- 16634029
TI  - Immune surveillance in multiple sclerosis patients treated with natalizumab.
AB  - OBJECTIVE: Our objective was to test whether natalizumab, an antibody against
      very late activating antigen (VLA)-4, interferes with central nervous system
      immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes
      in cerebrospinal fluid (CSF) and peripheral blood. METHODS: Cell numbers and
      cellular phenotypes in CSF and peripheral blood were analyzed in multiple
      sclerosis (MS) patients treated with natalizumab, untreated MS patients, and
      patients with other neurological disease (OND). JC virus DNA in the CSF and
      peripheral blood was quantified by kinetic polymerase chain reaction. RESULTS:
      CSF leukocyte counts, CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD138(+)
      plasma cells were significantly lower in natalizumab-treated MS patients compared
      with OND patients and untreated MS patients. JC virus DNA was not detected in CSF
      or peripheral blood from natalizumab-treated patients. Six months after cessation
      of natalizumab therapy, low lymphocyte counts in the CSF persisted. The patient
      with the highest total leukocyte and CD4(+) and CD8(+)T-cell counts in the CSF
      experienced a clinical relapse. INTERPRETATION: These data suggest that
      natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF
      and are consistent with the hypothesis that natalizumab impairs immune
      surveillance of the central nervous system.

PMID- 16634030
TI  - Complex segregation analysis of Parkinson's disease: The Mayo Clinic Family
      Study.
AB  - OBJECTIVE: To conduct complex segregation analyses of Parkinson's disease (PD).
      METHODS: Data on the familial aggregation of PD remain conflicting. We conducted
      a historical cohort study of 1,234 relatives of 162 patients with PD
      representative of people of Olmsted County, MN, and of 3,009 relatives of 411
      patients with PD referred to the Mayo Clinic. Relatives were interviewed and
      screened for parkinsonism either directly or through a proxy, those who screened
      positive were examined, or a copy of their medical record was obtained to confirm
      the diagnosis. For subjects who resided in Olmsted County, additional information
      was obtained from the archives of the Olmsted County Historical Society and from
      a records-linkage system. RESULTS: Thirty-two relatives of population-based
      probands and 69 relatives of referral patients developed PD (101 in total).
      Combining population-based and referral samples, the model that best explained
      the familial clustering of PD overall was a major gene with additive effect on
      the penetrance. This model predicted an average decrease in age at onset of PD of
      approximately 18 years for each copy of the putative high-risk allele. The best
      fitting model for younger onset PD (age <or= 59 years) was an autosomal recessive
      model. The best fitting models for older onset PD (age > 59 years) were a
      recessive or an additive model. INTERPRETATION: The familial aggregation of PD
      may be explained in part by a major gene with additive effect on the penetrance.

PMID- 16634031
TI  - Magnetic source imaging versus intracranial electroencephalogram in epilepsy
      surgery: a prospective study.
AB  - OBJECTIVE: Noninvasive brain imaging tests can potentially supplement or even
      replace the use of intracranial electroencephalogram (ICEEG), an invasive, costly
      procedure used in presurgical epilepsy evaluation. This study prospectively
      examined the agreement between magnetic source imaging (MSI) and ICEEG
      localization in epilepsy surgery candidates. METHODS: Patients completing video
      monitoring with scalp EEG who had intractable partial epilepsy based on ictal
      electro-clinico-anatomical features were screened. Forty-nine enrolled patients
      (mean age, 27 years; range, 1-61 years) completed MSI and ICEEG studies.
      Decisions about ICEEG and surgery were made at a consensus conference where MSI
      could only influence ICEEG coverage by indicating supplemental coverage to that
      already planned by an original hypothesis. RESULTS: The positive predictive value
      of MSI for seizure localization was 82 to 90%, depending on whether computed
      against ICEEG alone or in combination with surgical outcome. The kappa score of
      agreement for MSI with ICEEG was 0.2744 (p < 0.01) INTERPRETATION: MSI yields
      localizing information with a high positive predictive value in epilepsy surgery
      candidates who typically require ICEEG. This finding suggests that enough
      clinical validity exists for MSI to potentially replace ICEEG for seizure
      localization.

PMID- 16634032
TI  - Early-onset familial parkinsonism due to POLG mutations.
AB  - OBJECTIVE: To define the molecular etiology of early-onset parkinsonism and
      peripheral neuropathy. METHODS: Two sisters had early-onset parkinsonism
      (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture,
      and rigidity), together with clinical and electrophysiological signs of
      sensorimotor axonal peripheral neuropathy. RESULTS: No mutations were found in
      the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c
      oxidase-negative fibers, and biochemistry showed decreased activities of
      respiratory chain complexes containing mitochondrial DNA-encoded subunits.
      Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction,
      and sequencing of the POLG gene showed that the patients were compound
      heterozygous for two patogenic mutations. INTERPRETATION: POLG mutations can
      cause early-onset parkinsonism in the absence of progressive external
      ophthalmoplegia.

PMID- 16634033
TI  - Rapid diagnosis of glycine encephalopathy by 13C-glycine breath test.
AB  - OBJECTIVE: It is currently problematic to confirm the clinical diagnosis of
      glycine encephalopathy, requiring either invasive liver biopsy for enzymatic
      analysis of the glycine cleavage system or exhaustive mutation analysis. Because
      the glycine cleavage system breaks down glycine generating carbon dioxide, we
      suppose that the glycine cleavage system activity could be evaluated in vivo by
      measuring exhaled (13)CO(2) after administration of [1-(13)C]glycine. METHODS:
      The [1-(13)C]glycine breath test was performed in 10 control subjects and 5
      glycine encephalopathy patients with GLDC mutation, including 1 patient with mild
      glycine encephalopathy. RESULTS: All the patients showed lower (13)CO(2)
      excretion than any control subject. INTERPRETATION: Not only typical GE but also
      atypical GE can be reliably diagnosed by the (13)C-glycine breath test. Because
      it is rapid, non-invasive, and requires little expertise, the breath test could
      be useful as a standard test for diagnosing GE.

PMID- 16634034
TI  - Heterogeneity of voxel-based morphometry findings in Tourette's syndrome: an
      effect of age?

PMID- 16634035
TI  - Natalizumab effects on immune cell responses in multiple sclerosis.
AB  - OBJECTIVE: Our objective was to study in vivo biological effects of natalizumab
      on immune cell phenotype and function in multiple sclerosis (MS) patients.
      METHODS: Blood was obtained before and after serial monthly natalizumab infusions
      to track functional expression of VLA-4 and migratory capacity of immune cells.
      The impact of infusion on activation thresholds of immune cells was evaluated.
      RESULTS: Preinfusion VLA-4 expression differed across immune cell subsets.
      Natalizumab significantly, albeit partially, diminished VLA-4 expression on
      circulating immune cells. Cell subsets were differentially affected. Treatment
      significantly decreased migratory capacity of immune cells, correlating well with
      changes in VLA-4 expression. Effects of a single dose were not saturating and did
      not persist through the monthly dose interval. Infusion effect varied across
      patients but was remarkably stable in individual patients, over multiple
      infusions. Treatment significantly modulated proliferative responses of immune
      cells. INTERPRETATION: To our knowledge, we provide first proof of concept that
      natalizumab diminishes migratory capacity of immune cells. Our prospective study
      further shows that effects of therapy likely (1) differ for distinct immune cell
      subsets, (2) are not sustained over current dose interval, (3) have unique
      profiles in individual patients, and (4) include modulation of activation
      threshold of immune cells. Monitoring these parameters could be relevant to
      ongoing safety and efficacy considerations.

PMID- 16634036
TI  - Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar
      affect in multiple sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing
      dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice
      daily, for the treatment of pseudobulbar affect over a 12-week period in multiple
      sclerosis patients. METHODS: A total of 150 patients were randomized in a double
      blind, placebo-controlled study to assess pseudobulbar affect with the validated
      Center for Neurologic Study-Lability Scale. Each patient also recorded the number
      of episodes experienced between visits, estimated quality of life and quality of
      relationships on visual analog scales, and completed a pain rating scale.
      RESULTS: Patients receiving DM/Q had greater reductions in Center for Neurologic
      Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all
      clinic visits (days 15, 29, 57, and 85). All secondary end points also favored
      DM/Q, including the number of crying or laughing episodes (p <or= 0.0077),
      quality of life (p < 0.0001), quality of relationships (p = 0.0001), and pain
      intensity score (p = 0.0271). DM/Q was well tolerated; only dizziness occurred
      with greater frequency than with placebo. INTERPRETATION: Results in multiple
      sclerosis patients were similar to those of a previous study in amyotrophic
      lateral sclerosis, demonstrating that DM/Q may be beneficial in treating
      potentially disabling pseudobulbar affect in a variety of neurological disorders.

PMID- 16634037
TI  - High prevalence and phenotype-genotype correlations of limb girdle muscular
      dystrophy type 2I in Denmark.
AB  - OBJECTIVES: The prevalence of limb girdle muscular dystrophy type 2I (LGMD2I) in
      northern Europe is unknown. We investigated this and the genotype-phenotype
      relation in LGMD2I. METHODS: Prospective clinical and molecular screening of 118
      Danish patients registered with LGMD was performed to divide patients into LGMD
      subtypes. RESULTS: One hundred three patients fulfilled the clinical criteria for
      LGMD2. Thirty-eight had LGMD2I (27 homozygous, 11 compound heterozygous for
      826C>A), 23 had sarcoglycanopathy, 2 dysferlinopathy, 12 calpainopathy, and 4
      Becker muscular dystrophy. The 24 patients with no molecular diagnosis did not
      harbor fukutin-related protein gene (FKRP) mutations. A clear clinical
      delineation was found between patients homozygous and compound heterozygous for
      the 826C>A mutation. Homozygous patients had later debut, milder clinical
      progression, and less muscle weakness compared with compound heterozygous
      patients, who were all wheelchair bound by their mid-20s. Impaired cardiac pump
      function was found in both groups. INTERPRETATION: This study reports a different
      distribution of LGMD subtypes in Denmark than seen in other geographic regions,
      with a threefold to fourfold higher prevalence of LGMD2I than elsewhere. The
      findings support a clear clinical delineation between patients homozygous and
      compound heterozygous for the 826C>A mutation in FKRP. The findings suggest that,
      in the studied region, screening for the 826C>A mutation will identify all
      persons with LGMD2I.

PMID- 16634038
TI  - Cortical and spinal abnormalities in psychogenic dystonia.
AB  - OBJECTIVE: The pathophysiology of psychogenic dystonia has not been examined, but
      a growing body of literature suggests that abnormal sensory input from repetitive
      movements can lead to plastic cortical changes. Reduced cortical and spinal
      inhibition is well documented in organic dystonia. We tested the hypothesis that
      aberrant sensory input associated with abnormal posture may cause similar
      abnormalities by testing patients with psychogenic dystonia. METHODS: We assessed
      cortical and spinal inhibitory circuits and cortical activity associated with
      voluntary movement in 10 patients with clinically definite psychogenic dystonia,
      8 patients with organic dystonia, and 12 age-matched healthy control subjects.
      RESULTS: Three measures of cortical inhibition, resting short- and long-interval
      intracortical inhibition and cortical silent period, were reduced in both
      psychogenic dystonia and organic dystonia. Cutaneous silent period mediated by
      spinal circuitries was increased in psychogenic and organic dystonia. Forearm
      spinal reciprocal inhibition was reduced in psychogenic dystonia. INTERPRETATION:
      Psychogenic and organic dystonia share similar physiological abnormalities.
      Previous findings of abnormal cortical and spinal excitability in organic
      dystonia may, in part, be a consequence rather than a cause of dystonia.
      Alternatively, these findings may represent endophenotypic abnormalities that
      predispose to both types of dystonia.

PMID- 16634039
TI  - Tumor necrosis factor-alpha contributes to below-level neuropathic pain after
      spinal cord injury.
AB  - OBJECTIVE: Our objective was to elucidate the mechanisms responsible for below
      level pain after partial spinal cord injury (SCI). METHODS: We used lateral
      hemisection to model central neuropathic pain and herpes simplex viral (HSV)
      vector-mediated transfer of the cleaved soluble receptor for tumor necrosis
      factor-alpha (TNF-alpha) to evaluate the role of TNF-alpha in the pathogenesis of
      below-level pain. RESULTS: We found activation of microglia and increased
      expression of TNF-alpha below the level of the lesion in the lumbar spinal cord
      after T13 lateral hemisection that correlated with emergence of mechanical
      allodynia in the hind limbs of rats. Lumbar TNF-alpha had an apparent molecular
      weight of 27 kDa, consistent with the full-length transmembrane form of the
      protein (mTNF-alpha). Expression of the p55 TNF soluble receptor (sTNFRs) by HSV
      mediated gene transfer resulted in reduced pain behavior and a decreased number
      of ED1-positive cells, as well as decreased phosphorylation of the p38 MAP kinase
      (p-p38) and diminished expression of mTNF-alpha in the dorsal horn.
      INTERPRETATION: These results suggest that expression of mTNF-alpha after injury
      is related to development of pain, and that reverse signaling through mTNF-alpha
      by sTNFR at that level reduces cellular markers of inflammatory response and pain
      related behavior.

PMID- 16634041
TI  - Cellular and molecular mechanisms of neural repair after stroke: making waves.
AB  - Stroke is associated with a limited degree of functional recovery. Imaging
      studies in humans have shown that reorganization in periinfarct and connected
      cortical areas most closely correlates with functional recovery after stroke. On
      a cellular level, two major regenerative events occur in periinfarct cortex:
      axons sprout new connections and establish novel projection patterns, and newly
      born immature neurons migrate into periinfarct cortex. Stroke induces a unique
      microenvironment for axonal sprouting in periinfarct cortex, in which growth
      inhibitory molecules are reduced for 1 month after the infarct. During this
      period, neurons activate growth-promoting genes in successive waves. Neurogenesis
      also occurs through waves of migration of immature neurons from their origin in
      the subventricular zone into periinfarct cortex. This migration is mediated, in
      part, by the cytokine erythropoietin. These data indicate that the cellular
      environment after stroke is far from one of just death and destruction, but
      rather involves a longer evolving process of neuronal regeneration. Poststroke
      neuronal regeneration is characterized by waves of specific cellular and
      molecular events. Manipulating these waves of regeneration may provide for novel
      therapies that will improve recovery after stroke.

PMID- 16634042
TI  - Complementary patterns of gene expression by human oligodendrocyte progenitors
      and their environment predict determinants of progenitor maintenance and
      differentiation.
AB  - OBJECTIVE: Glial progenitor cells are abundant in adult human white matter. This
      study was designed to identify signaling pathways regulating their self-renewal
      and fate. METHODS: We compared the transcriptional profiles of freshly sorted
      adult human white matter progenitor cells (WMPCs), purified by A2B5-based
      immunomagnetic sorting, with those of the white matter from which they derived.
      RESULTS: We identified 132 genes differentially expressed by WMPCs; these
      included principal components of five receptor-defined signaling pathways,
      represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3
      fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase
      beta/zeta (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the
      bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and
      activin membrane-bound inhibitor), suggesting tonic defense against BMP
      signaling. Differential overexpression of RTPZ was accompanied by that of its
      modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate
      proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed
      to the RTPZ inhibitor bpV(phen), or lentiviral-shRNAi against RTPZ, WMPCs
      differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were
      antagonized by BMP4, astrocytic differentiation was induced, which was reversible
      by noggin. INTERPRETATION: The RTPZ and BMP pathways regulate the self
      maintenance of adult human WMPCs, and can be modulated to induce their
      oligodendrocytic or astrocytic differentiation. As such, they provide targets by
      which to productively mobilize resident progenitor cells of the adult human
      brain.

PMID- 16634043
TI  - Codep: maximizing co-evolutionary interdependencies to discover interacting
      proteins.
AB  - Approaches for the determination of interacting partners from different protein
      families (such as ligands and their receptors) have made use of the property that
      interacting proteins follow similar patterns and relative rates of evolution.
      Interacting protein partners can then be predicted from the similarity of their
      phylogenetic trees or evolutionary distances matrices. We present a novel method
      called Codep, for the determination of interacting protein partners by maximizing
      co-evolutionary signals. The order of sequences in the multiple sequence
      alignments from two protein families is determined in such a manner as to
      maximize the similarity of substitution patterns at amino acid sites in the two
      alignments and, thus, phylogenetic congruency. This is achieved by maximizing the
      total number of interdependencies of amino acids sites between the alignments.
      Once ordered, the corresponding sequences in the two alignments indicate the
      predicted interacting partners. We demonstrate the efficacy of this approach with
      computer simulations and in analyses of several protein families. A program
      implementing our method, Codep, is freely available to academic users from our
      website: http://www.uhnresearch.ca/labs/tillier/.

PMID- 16634045
TI  - Molecular genetic analysis of Wanggu remains, Inner Mongolia, China.
AB  - The Wanggu tribe, which contributed significantly to the foundation of the Yuan
      Dynasty, was one of the groups living on the Mongolian steppes during the Jin
      Yuan period (AD 1127-1368) of Chinese history. However, there has been both
      archaeological and historical dispute regarding the origin of the ancient tribe.
      Recently, we discovered human remains of the Wanggu tribe in the Chengbozi
      cemetery in the Siziwang Banner of Inner Mongolia, China. To investigate the
      genetic structure of the Wanggu tribe and to trace the origins of the tribe at a
      molecular level, we analyzed the control-region sequences and coding regions of
      mitochondrial DNA (mtDNA) from the remains by direct sequencing and restriction
      fragment length polymorphism analysis. In combination with mtDNA data of 15
      extant Eurasian populations, we performed phylogenetic analysis and
      multidimensional scaling analysis. Our results show that the genetic structure of
      the Wanggu tribe in the Jin-Yuan period is a complex matriline, containing
      admixture from both Asian and European populations. In addition, we reveal that
      on the basis of mtDNA data, the ancient tribe may share a recent common ancestor
      with the Turkic-speaking Uzbeks and Uighurs.

PMID- 16634046
TI  - Osteoporosis in a population from medieval Norway.
AB  - Modern populations from Norway and England differ in their experience of
      osteoporosis, the former showing lower bone mineral density (BMD) and a higher
      fragility fracture rate. The aim of the present work was to investigate whether
      this was also the case during the Middle Ages. Age-dependent loss of BMD in the
      proximal femur was assessed using dual X-ray absorptiometry (DXA) in male and
      female adult skeletons from a cemetery in the medieval town of Trondheim, Norway.
      Fracture prevalence was also investigated. Results were compared with those
      previously reported for a skeletal series from Wharram Percy, a deserted medieval
      village in England. Results indicate that peak BMD and patterns of age-related
      loss of BMD in the Norwegian and the English group were similar. Among females,
      the prevalence of osteoporotic fractures was greater in the Norwegian than in the
      English population. The BMD results suggest that differences in BMD between
      English and Norwegians are of recent origin, although given the fairly modest
      sample sizes, further work is needed to confirm this. Reasons for the greater
      prevalence of osteoporotic fractures in women in the Norwegian skeletal series
      are unclear, but the colder climate and greater frequency of hard surfaces may
      have meant that falls were more frequent, and when they occurred, were more
      likely to result in fractures than in the rural English group.

PMID- 16634047
TI  - Spondylolysis, spondylolisthesis, and lumbo-sacral morphology in a medieval
      English skeletal population.
AB  - The prevalence of spondylolysis and spondylolisthesis was studied in an adult
      skeletal series from a rural English medieval archaeological site. Attempts were
      made to evaluate the association of three aspects of lumbo-sacral skeletal
      morphology (pelvic incidence (a measure of the anterior inclination of the sacral
      table), lumbar transverse process width, and the presence of lumbo-sacral spina
      bifida occulta) with spondylolysis and spondylolisthesis. Results indicated a
      high prevalence of spondylolysis compared with a modern reference population, but
      few cases of spondylolisthesis were identified. Analysis of prevalence with
      respect to age suggests that in the study population, pars interarticularis
      defects generally formed late in the growth period or early in adult life. The
      study group showed a high mean pelvic incidence compared with modern Western
      Europeans, indicating a more steeply inclined sacral table, which may have
      elevated the risk of developing pars interarticularis defects. However, no
      statistically valid association could be demonstrated between the
      presence/absence of spondylolysis and pelvic incidence in the study material.
      There was no evidence for a link between lumbar transverse process index or lumbo
      sacral spina bifida occulta and spondylolysis/spondylolisthesis. It is concluded
      that the potential role of lumbo-sacral morphology, as well as of activity
      regimes, should be considered when interpreting spondylolysis in
      paleopathological studies. If the frequency of spondylolysis is to some extent an
      indicator of past activity regimes, it may reflect lifestyle in younger
      individuals rather than in mature adults. Further work investigating the link
      between spondylolysis and lumbo-sacral morphological variables in premodern
      populations would be of value.

PMID- 16634048
TI  - Craniometic variation in the Azapa Valley: reply to Sutter and Mertz (2004).

PMID- 16634050
TI  - Binge eating and purging in a multi-ethnic community sample.
AB  - OBJECTIVE: The purpose of the present study is to document the frequency of three
      eating disorder-related behaviors (binge eating; self-induced vomiting; and use
      of laxatives, diuretics, and diet pills) among a multi-ethnic community sample.
      METHOD: A questionnaire was administered to 1225 Hispanic, Asian, black, and
      white women and men. Participants responded to items (based on DSM-IV diagnostic
      criteria for eating disorders) about binge eating and purging behavior. RESULTS:
      Binge eating and purging were more common among women than among men in Hispanic,
      black, and white subsamples (frequency rates were similar among Asian men and
      women). Ethnic differences were found in frequency of purging among women
      (ethnicity was not associated with behavior rates among men). Fewer Asian than
      Hispanic, black, and white women induced vomiting and used laxatives, diuretics,
      and diet pills as weight control methods. CONCLUSION: The fact that frequency
      rates differed as a function of participant sex and ethnicity underscores the
      importance of considering both of these group variables when examining disordered
      eating and weight control behaviors.

PMID- 16634051
TI  - Cohabitation reduces bulimic symptoms in young women.
AB  - OBJECTIVE: This current study examines the relationship between cohabitation and
      changes in bulimic symptoms in young adults. METHOD: A sample of 2601 initially
      noncohabitating adolescents was followed over a 5-year period and growth curve
      analyses were conducted. RESULTS: Females who over the course of the study moved
      in with a partner had greater decreases in bulimic symptoms compared with female
      noncohabitators. This difference was highly significant, even if small in size.
      No such effect was found in males. When examining the frequency of bulimic
      behaviors in females, the most socially unacceptable bulimic behaviors were those
      most reduced by cohabitation, whereas less obtrusive bulimic behaviors were not
      reduced. CONCLUSION: The results give some indication that social control
      exercised in close relationships may account for decreased bulimic symptoms in
      female cohabitators. Further studies are needed to confirm the importance of
      social control and to examine how it affects symptom reduction.

PMID- 16634052
TI  - Sexual orientation as a risk factor for bulimic symptoms.
AB  - OBJECTIVE: This study was carried out to examine whether sexual orientation
      predicts future bulimic symptoms and whether alleged risk factors associated with
      non-heterosexual sexual orientation explain the increased risk. METHOD: A
      nationally representative sample of Norwegian high school students (age 14-19;
      N=2,924) completed self-reports about bulimic symptoms by means of the Bulimic
      Investigatory Test-Edinborough (BITE), same-sex sexual experience, degree of
      sexual attraction to the same sex, and alleged risk factors. They were reexamined
      5 years later (T2). RESULTS: Same-sex sexual experience before T1 increased the
      prevalence of bulimic symptoms at T2. Males who were attracted to the same sex at
      T1 had higher odds for bulimic symptoms compared with heterosexual males. These
      associations were still significant after controlling for initial bulimic
      symptoms and alleged risk factors. CONCLUSION: Same-sex sexual experience in both
      genders and non-heterosexual sexual attraction among males predict future bulimic
      symptoms. Commonly advocated explanations for this elevated risk were not
      supported.

PMID- 16634054
TI  - Cervical paraspinal spontaneous activity in asymptomatic subjects.
AB  - Paraspinal fibrillation potentials or positive sharp waves (PSWs) reportedly may
      be the only electrodiagnostic abnormality in patients with radiculopathies.
      However, spontaneous activity may be present in muscles of asymptomatic subjects.
      To determine whether abnormal spontaneous activity in the cervical paraspinal
      muscles is clinically relevant, we evaluated the prevalence of such activity in
      asymptomatic individuals and examined its relationship with age. Sixty-six
      asymptomatic subjects underwent a needle electromyographic examination of the
      paraspinal muscles bilaterally at the C5/6 and C6/7 levels. All of the recorded
      potentials were captured and their firing rates and waveforms were evaluated. The
      potentials were considered to be abnormal if reproducible trains of PSWs or
      fibrillation potentials were present. Eight of the 66 (12%) subjects showed PSWs,
      five bilaterally; none showed fibrillation potentials. A statistical analysis for
      the effect of age could not be performed due to the small sample size. Because
      electromyographic cervical paraspinal abnormalities can be found in asymptomatic
      subjects, caution should be exercised when attributing the etiology of neck pain
      to radiculopathy if the only electrodiagnostic findings are electromyographic
      cervical paraspinal abnormalities.

PMID- 16634055
TI  - Novel role for aspartoacylase in regulation of BDNF and timing of postnatal
      oligodendrogenesis.
AB  - Neuronal growth factors are thought to exert a significant degree of control over
      postnatal oligodendrogenesis, but mechanisms by which these factors
      coordinateoligodendrocyte development with the maturation of neural networks are
      poorly characterized. We present here a developmental analysis of aspartoacylase
      (Aspa)-null tremor rats and show a potential role for this hydrolytic enzyme in
      the regulation of a postnatal neurotrophic stimulus that impacts on early stages
      of oligodendrocyte differentiation. Abnormally high levels of brain-derived
      neurotrophic factor (BDNF) expression in the Aspa-null Tremor brain are
      associated with dysregulated oligodendrogenesis at a stage in development
      normally characterized by high levels of Aspa expression. BDNF promotes the
      survival of proliferating cells during the early stages of oligodendrocyte
      maturation in vitro, but seems to compromise the ability of these cells to
      populate the cortex in vivo. Aspartoacylase activity in oligodendrocytes is shown
      to provide for the negative regulation of BDNF in neurons, thereby determining
      the availability of a developmental stimulus via a mechanism that links
      oligodendroglial differentiation with neuronal maturation.

PMID- 16634056
TI  - Comparative study of microglia activation induced by amyloid-beta and prion
      peptides: role in neurodegeneration.
AB  - The inflammatory responses in Alzheimer's disease (AD) and prion-related
      encephalopathies (PRE) are dominated by microglia activation. Several studies
      have reported that the amyloid-beta (Abeta) peptides, which are associated with
      AD, and the pathogenic isoform of prion protein (PrPSc) have a crucial role in
      neuronal death and gliosis that occur in both of these disorders. In this study,
      we investigate whether Abeta and PrPSc cause microglia activation per se and
      whether these amyloidogenic peptides differentially affect these immunoeffector
      cells. In addition, we also determined whether substances released by Abeta- and
      PrP-activated microglia induce neuronal death. Cultures of rat brain microglia
      cells were treated with the synthetic peptides Abeta1-40, Abeta1-42 and PrP106
      126 for different time periods. The lipopolysaccharide was used as a positive
      control of microglia activation. Our results show that Abeta1-40 and PrP106-126
      caused similar morphological changes in microglia and increased the production of
      nitric oxide and hydroperoxides. An increase on inducible nitric oxide synthase
      expression was also observed in microglia treated with Abeta1-40 or PrP106.
      However, these peptides affected in a different manner the secretion of
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) secretion. In cocultures of
      microglia-neurons, it was observed that microglia treated with Abeta1-40 or
      PrP106-126 induced a comparable extent of neuronal death. The neutralizing
      antibody for IL-6 significantly reduced the neuronal death induced by Abeta- or
      PrP-activated microglia. Taken together, the data indicate that Abeta and PrP
      peptides caused microglia activation and differentially affected cytokine
      secretion. The IL-6 released by reactive microglia caused neuronal injury.

PMID- 16634057
TI  - Carpal tunnel syndrome in older adults.
AB  - The clinical and electrophysiologic characteristics of carpal tunnel syndrome
      (CTS) in elderly adults are not well established. We examined age differences in
      clinical, functional, and electrophysiologic features in elderly adults referred
      to a neuromuscular service for evaluation of symptoms suggestive of CTS. Of 415
      consecutive subjects referred over an 18-month period, 343 met clinical criteria
      for CTS. There were 158 young (<or=50 years), 115 middle-aged (51-64 years), and
      70 elderly adults (>or=65 years). There were no age differences in the duration
      of CTS symptoms, hand function, or presence of autonomic symptoms. The elderly
      adults had a higher prevalence of thenar weakness and thenar atrophy than younger
      subjects. Electrophysiologic abnormalities were more common and more severe in
      the older subjects. Our study shows that although there are no age differences in
      subjective complaints of CTS, older adults had objective clinical and
      electrophysiologic evidence of a more severe median nerve entrapment. The
      findings suggest that greater attention needs to be paid to objective evidence of
      CTS severity rather than subjective complaints when evaluating elderly adults
      presenting for clinical evaluation of CTS.

PMID- 16634058
TI  - Hypoosmolar conditions reduce extracellular volume fraction and enhance
      epileptiform activity in the CA3 region of the immature rat hippocampus.
AB  - The osmolarity of the extracellular space (ECS) compartment is an important
      factor determining the excitability of neuronal tissue. In the adult hippocampus
      an important role of osmolarity and ECS diffusion parameters on the
      susceptibility to epileptic events is well established, but the influence of hypo
      and hyperosmolar conditions on the immature hippocampus remains elusive. To
      investigate the influence of osmolarity on epileptiform activity, extracellular
      field potentials were recorded in the CA3 region of hippocampal slices of
      immature (postnatal days 4-7) Wistar rats. The ECS diffusion parameters were
      determined by the real-time tetramethylammonium (TMA+) iontophoretic method with
      ion-selective microelectrodes in immature hippocampal slices and showed a lack of
      diffusion anisotropy; a tortuosity of about 1.39; and a volume fraction, alpha,
      of 0.41 +/- 0.01 (n = 10 slices). A reduction in osmolarity of -90 mOsm induced a
      decrease in alpha to 0.17 +/- 0.02 (n = 4 slices). The frequency of epileptiform
      activity elicited in 10-50 microM 4-AP-containing low-Mg2+ solution was increased
      under -90 mOsm and -40 mOsm hypoosmolar conditions by 39.9% +/- 8.1% (n = 16) and
      24.1% +/- 4.8% (n = 10), respectively, whereas hyperosmolar solutions decreased
      the frequency. A -90-mOsm reduction in the osmolarity of low-Mg2+ solution
      induced epileptiform activity in nine of 19 slices. In summary, these results
      demonstrate that hypoosmolar conditions increased excitability and susceptibility
      to epileptiform activity in immature hippocampal slices, suggesting a functional
      role of the larger alpha in suppression of seizures.

PMID- 16634059
TI  - The stimulus-response curve and motor unit variability in normal subjects and
      subjects with amyotrophic lateral sclerosis.
AB  - The behavior and stability of motor units (MUs) in response to electrical
      stimulation of different intensities can be assessed with the stimulus-response
      curve, which is a graphical representation of the size of the compound muscle
      action potential (CMAP) in relation to stimulus intensity. To examine MU
      characteristics across the whole stimulus range, the variability of CMAP
      responses to electrical stimulation, and the differences that occur between
      normal and disease states, the curve was studied in 11 normal subjects and 16
      subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve
      showed a gradual increase in CMAP size with increasing stimulus intensity,
      although one or two discrete steps were sometimes observed in the upper half of
      the curve, indicating the activation of large MUs at higher intensities. In ALS
      subjects, large discrete steps, due to loss of MUs and collateral sprouting, were
      frequently present. Variability of the CMAP responses was greater than baseline
      variability, indicating variability of MU responses, and at certain levels this
      variability was up to 100 microVms. The stimulus-response curve shows differences
      between normal and ALS subjects and provides information on MU activation and
      variability throughout the curve.

PMID- 16634060
TI  - Rat Schwann cells express M1-M4 muscarinic receptor subtypes.
AB  - The expression of different muscarinic receptor subtypes was analyzed in immature
      Schwann cells obtained from sciatic nerve of 2-day neonatal rats. By using RT-PCR
      analysis, we demonstrated the presence of M1, M2, M3, and M4 receptor subtypes in
      cultured Schwann cells, with M2 displaying the highest expression levels.
      Muscarinic subtypes were also quantified by immunoprecipitation and [3H]QNB
      binding. With this approach, we found the levels of receptor expression to be M2
      > M3 > M1. M4 is expressed at very low levels, and M5 receptor was not
      detectable. Moreover, we also demonstrated that stimulation of the receptors by
      muscarinic agonists activates previously described signal transduction pathways,
      leading to a decrease of cAMP and an increase of IP3 levels not associated with
      an efficient intracellular Ca2+ release. The presence and activity of particular
      muscarinic receptors in immature Schwann cells suggest that ACh may play an
      important role in Schwann cell development.

PMID- 16634061
TI  - Muscle engraftment of myogenic progenitor cells following intraarterial
      transplantation.
AB  - Cell-based therapy continues to be a promising avenue for the treatment of
      Duchenne muscular dystrophy (DMD), an X-linked skeletal muscle-wasting disease.
      Recently, we demonstrated that freshly isolated myogenic progenitors contained
      within the adult skeletal muscle side population (SP) can engraft into dystrophic
      fibers of nonirradiated mdx(5cv) mice after intravenous transplantation.
      Engraftment rates, however, have not been therapeutically significant, achieving
      at most 1% of skeletal muscle myofibers expressing protein from donor-derived
      nuclei. To enhance the engraftment of transplanted myogenic progenitors, an
      intraarterial delivery method was adapted from a previously described procedure.
      Cultured, lentivirus-transduced skeletal muscle SP cells, derived from mdx(5cv)
      mice, were transplanted into the femoral artery of noninjured mdx(5cv) mice.
      Based on the expression of microdystrophin or green fluorescent protein (GFP)
      transgenes in host muscle, sections of the recipient muscles exhibited 5%-8% of
      skeletal muscle fibers expressing donor-derived transgenes. Further, donor muscle
      SP cells, which did not express any myogenic markers prior to transplant,
      expressed the satellite cell transcription factor, Pax7, and the muscle-specific
      intermediate filament, desmin, after extravasation into host muscle. The
      expression of these muscle-specific markers indicates that progenitors within the
      side population can differentiate along the myogenic lineage after intraarterial
      transplantation and extravasation into host muscle. Given that femoral artery
      catheterization is a common, safe clinical procedure and that the transplantation
      of cultured adult muscle progenitor cells has proven to be safe in mice, our data
      may represent a step toward the improvement of cell-based therapies for DMD and
      other myogenic disorders.

PMID- 16634062
TI  - Adaptation of the properties of spastic muscle with wrist extension deformity.
AB  - To show that human muscle may adapt to tendon transfer, adaptation of flexor
      carpi ulnaris (FCU) function was studied by measuring active and passive length
      force characteristics at initial operation and at reoperation in a case of
      extension deformity secondary to FCU tendon transfer. At reoperation, FCU was 20
      mm shorter; active force decreased approximately 10%, indicating atrophy; and
      passive force increased, reflecting increased stiffness. FCU fiber length was
      unchanged. The presented case shows that human forearm muscle may adapt to a
      transferred function.

PMID- 16634063
TI  - Molecular and cellular contractile dysfunction of dystrophic muscle from young
      mice.
AB  - The purpose of this study was to determine whether contractile protein
      alterations are responsible for force deficits in young dystrophic muscle.
      Contractility of intact extensor digitorum longus muscles and permeabilized
      fibers from wild-type (wt), dystrophin-deficient (mdx), and dystrophin/utrophin
      deficient (mdx:utrn-/-) mice aged 21 and 35 days was determined. Myosin
      structural dynamics were assessed by site-directed spin labeling and electron
      paramagnetic resonance spectroscopy. The principal finding was that force
      generation was depressed by approximately 20% in mdx muscles, but fiber Ca2+
      activated force and myosin structure were not different from wt animals,
      suggesting that contractile proteins are not responsible for the force deficits
      in those muscles. For mdx:utrn-/- mice, muscle and fiber forces were
      approximately 40% lower than wt and the fraction of strong-binding myosin during
      contraction was reduced by 13%. These data indicate that contractile protein
      alterations, in addition to myosin dysfunction, cause force deficit in muscles
      from young mdx:utrn-/- mice. Elucidating the molecular mechanisms underlying
      muscle weakness at the onset of disease is important for designing treatment
      strategies.

PMID- 16634064
TI  - Predictive model of muscle fatigue after spinal cord injury in humans.
AB  - The fatigability of paralyzed muscle limits its ability to deliver physiological
      loads to paralyzed extremities during repetitive electrical stimulation. The
      purposes of this study were to determine the reliability of measuring paralyzed
      muscle fatigue and to develop a model to predict the temporal changes in muscle
      fatigue that occur after spinal cord injury (SCI). Thirty-four subjects underwent
      soleus fatigue testing with a modified Burke electrical stimulation fatigue
      protocol. The between-day reliability of this protocol was high (intraclass
      correlation, 0.96). We fit the fatigue index (FI) data to a quadratic-linear
      segmental polynomial model. FI declined rapidly (0.3854 per year) for the first
      1.7 years, and more slowly (0.01 per year) thereafter. The rapid decline of FI
      immediately after SCI implies that a "window of opportunity" exists for the
      clinician if the goal is to prevent these changes. Understanding the timing of
      change in muscle endurance properties (and, therefore, load-generating capacity)
      after SCI may assist clinicians when developing therapeutic interventions to
      maintain musculoskeletal integrity.

PMID- 16634065
TI  - Protective effect of D609 against amyloid-beta1-42-induced oxidative modification
      of neuronal proteins: redox proteomics study.
AB  - Oxidative stress has been implicated in the pathophysiology of a number of
      diseases, including neurodegenerative disorders such as Alzheimer's disease (AD),
      a neurodegenerative disorder associated with cognitive decline and enhanced
      oxidative stress. Amyloid-beta peptide(1-42) (Abeta(1-42)), one of the main
      component of senile plaques, can induce in vitro and in vivo oxidative damage to
      neuronal cells through its ability to produce free radicals. The aim of this
      study was to investigate the protective effect of the xanthate D609 on Abeta(1
      42)-induced protein oxidation by using a redox proteomics approach. D609 was
      recently found to be a free radical scavenger and antioxidant. In the present
      study, rat primary neuronal cells were pretreated with 50 microM of D609,
      followed by incubation with 10 microM Abeta(1-42) for 24 hr. In the cells treated
      with Abeta(1-42) alone, four proteins that were significantly oxidized were
      identified: glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, malate
      dehydrogenase, and 14-3-3 zeta. Pretreatment of neuronal cultures with D609 prior
      to Abeta(1-42) protected all the identified oxidized proteins in the present
      study against Abeta(1-42)-mediated protein oxidation. Therefore, D609 may
      ameliorate the Abeta(1-42)-induced oxidative modification. We discuss the
      implications of these Abeta(1-42)-mediated oxidatively modified proteins for AD
      pathology and for potential therapeutic intervention in this dementing disorder.

PMID- 16634066
TI  - Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical
      neurons against amyloid-beta peptide 1-42-mediated oxidative stress and
      neurotoxicity: implications for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by loss of memory and cognition and by senile plaques and
      neurofibrillary tangles in brain. Amyloid-beta peptide, particularly the 42-amino
      acid peptide (Abeta(1-42)), is a principal component of senile plaques and is
      thought to be central to the pathogenesis of the disease. The AD brain is under
      significant oxidative stress, and Abeta(1-42) peptide is known to cause oxidative
      stress in vitro and in vivo. Acetyl-L-carnitine (ALCAR) is an endogenous
      mitochondrial membrane compound that helps to maintain mitochondrial
      bioenergetics and lowers the increased oxidative stress associated with aging.
      Glutathione (GSH) is an important endogenous antioxidant, and its levels have
      been shown to decrease with aging. Administration of ALCAR increases cellular
      levels of GSH in rat astrocytes. In the current study, we investigated whether
      ALCAR plays a protective role in cortical neuronal cells against Abeta(1-42)
      mediated oxidative stress and neurotoxicity. Decreased cell survival in neuronal
      cultures treated with Abeta(1-42) correlated with an increase in protein
      oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (4-hydroxy-2
      nonenal) formation. Pretreatment of primary cortical neuronal cultures with ALCAR
      significantly attenuated Abeta(1-42)-induced cytotoxicity, protein oxidation,
      lipid peroxidation, and apoptosis in a dose-dependent manner. Addition of ALCAR
      to neurons also led to an elevated cellular GSH and heat shock proteins (HSPs)
      levels compared with untreated control cells. Our results suggest that ALCAR
      exerts protective effects against Abeta(1-42) toxicity and oxidative stress in
      part by up-regulating the levels of GSH and HSPs. This evidence supports the
      pharmacological potential of acetyl carnitine in the management of Abeta(1-42)
      induced oxidative stress and neurotoxicity. Therefore, ALCAR may be useful as a
      possible therapeutic strategy for patients with AD.

PMID- 16634067
TI  - Role of the plasma membrane calcium adenosine triphosphatase on domoate-induced
      intracellular acidification in primary cultures of cerebelar granule cells.
AB  - Changes in intracellular pH (pH(i)) and cytosolic calcium concentration
      ([Ca(2+)](c)) caused by the glutamate agonist domoate (DOM) were studied in
      single cultured mouse cerebellar granule cells (CGC) by using the fluorescent
      probes 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF
      AM) and simultaneous evaluation of cytosolic calcium concentration with the
      fluorescent dye Fura-2 acetoxymethyl ester (Fura-2 AM). DOM caused a
      concentration-dependent increase in [Ca(2+)](c) and a concentration-dependent
      intracellular acidification of CGC. DOM-induced intracellular acidification was
      completely abolished by the use of Ca(2+)-free medium, suggesting that it was due
      mostly to an influx of extracellular calcium. The pH(i) decrease caused by DOM
      was also completely blocked in the presence of the AMPA/kainate receptor
      antagonist CNQX, indicating that the DOM-induced intracellular acidification was
      caused by DOM activation of the AMPA/kainate subtype of glutamate receptors.
      Different mechanisms that could be involved in DOM-induced pH(i) decrease, such
      as displacement of H(+) by Ca(2+) from a common intracellular binding site, DOM
      induced alteration of pH(i) regulation mechanisms, and a possible acidification
      caused by DOM-induced increase of mitochondrial Ca(2+) uptake, were excluded. DOM
      induced intracellular acidification was completely prevented by inhibitors of the
      plasma membrane calcium adenosine triphosphatase (ATPase) (PMCA), including
      orthovanadate, lanthanum extracellular pH of 8.5, and the specific PMCA inhibitor
      caloxin 2A1. Our results therefore indicate that PMCA is involved in DOM-induced
      intracellular acidification in primary cultures of CGC. Simultaneous recording of
      [Ca(2+)](c) and pH(i) indicates that the increase in intracellular calcium evoked
      by DOM will activate the calcium extrusion mechanisms through the calcium pump,
      which, in turn, will decrease intracellular pH by countertransport of H(+) ions.

PMID- 16634068
TI  - In vivo protective effects of ferulic acid ethyl ester against amyloid-beta
      peptide 1-42-induced oxidative stress.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the
      deposition of amyloid-beta peptide (Abeta), a peptide that as both oligomers and
      fibrils is believed to play a central role in the development and progress of AD
      by inducing oxidative stress in brain. Therefore, treatment with antioxidants
      might, in principle, prevent propagation of tissue damage and neurological
      dysfunction. The aim of the present study was to investigate the in vivo
      protective effect of the antioxidant compound ferulic acid ethyl ester (FAEE)
      against Abeta-induced oxidative damage on isolated synaptosomes. Gerbils were
      injected intraperitoneally (i.p.) with FAEE or with dimethylsulfoxide, and
      synaptosomes were isolated from the brain. Synaptosomes isolated from FAEE
      injected gerbils and then treated ex vivo with Abeta(1-42) showed a significant
      decrease in oxidative stress parameters: reactive oxygen species levels, protein
      oxidation (protein carbonyl and 3-nitrotyrosine levels), and lipid peroxidation
      (4-hydroxy-2-nonenal levels). Consistent with these results, both FAEE and
      Abeta(1-42) increased levels of antioxidant defense systems, evidenced by
      increased levels of heme oxygenase 1 and heat shock protein 72. FAEE led to
      decreased levels of inducible nitric oxide synthase. These results are discussed
      with potential therapeutic implications of FAEE, a brain accessible,
      multifunctional antioxidant compound, for AD involving modulation of free
      radicals generated by Abeta.

PMID- 16634069
TI  - Transport of levovirin prodrugs in the human intestinal Caco-2 cell line.
AB  - The transport of 10 amino acid ester prodrugs of levovirin (LVV) was investigated
      in the human intestinal Caco-2 cell line in order to overcome the poor oral
      bioavailability of LVV, an investigational drug for the treatment of hepatitis C
      infection. The prodrugs were designed to improve the permeability of LVV across
      the intestinal epithelium by targeting the di/tri-peptide carrier, PepT1. Caco-2
      cell monolayers were employed to study the transport and hydrolysis properties of
      the prodrugs. Among all mono amino acid ester prodrugs studied, the LVV-5'-(L)
      valine prodrug (R1518) exhibited the maximum increase (48-fold) in permeability
      with nearly complete conversion to LVV within 1 h. Di-amino acid esters did not
      offer significant enhancement in permeability comparing with mono amino acid
      esters and exhibited slower conversion to LVV in Caco2 cell monolayers.
      Pharmacokinetic screening studies of the prodrugs in rats yielded the highest
      fold increase (6.9-fold) of AUC with R1518 and in general displayed a similar
      trend to that observed in increases of permeability in Caco-2 cells. Mechanisms
      involved in the Caco-2 cell transport of R1518 were also investigated. Results of
      bi-directional transport studies support the involvement of carrier-mediated
      transport mechanisms for R1518, but not for the LVV-5'-(D)-valine prodrug or LVV.
      Moreover, the permeability of R1518 was found to be proton dependent. PepT1
      mediated transport of R1518 was supported by results of competitive transport
      studies of R1518 with the PepT1 substrates enalapril, Gly-Sar, valganciclovir,
      and cephalexin. R1518 was also found to inhibit the permeability of
      valganciclovir and cephalexin. These results suggest that R1518 is a PepT1
      substrate as well as an inhibitor.

PMID- 16634070
TI  - Core imprint cytology of screen-detected breast lesions is predictive of the
      histologic results.
AB  - BACKGROUND: In multidisciplinary assessment clinics for screen-detected breast
      lesions, onsite cytopathologists provide immediate results of fine-needle
      aspiration biopsies (FNABs) and this information is used for patient counseling
      and treatment planning. Such consultation is not possible for the increasing
      proportion of lesions that are being assessed by core biopsy. If core imprint
      cytology (CIC) of breast cores can be shown to be reliable in a significant
      proportion of screen-detected lesions, this technique may be of clinical value in
      such clinics. METHODS: In the setting of a large, accredited, population-based
      breast cancer screening program, prospective results of CIC were gathered on 567
      lesions and correlated with the results of core biopsy to determine the
      performance indicators for CIC. RESULTS: The positive predictive value of a
      diagnosis of malignancy on CIC was 98.2% and the negative predictive value was
      77.8%. The absolute sensitivity was 42.2%, complete sensitivity (inclusive of
      suspicious and atypical results) was 86.4%, absolute specificity was 56.3%, and
      total specificity (inclusive of acellular imprints) was 83.7%. The 2 false
      positive imprints had atypical ductal hyperplasia on core histology but were
      found to be ductal carcinoma in situ (DCIS) on excision. False-negative imprints
      are a greater challenge, with 13.6% of malignant lesions producing benign
      appearing or acellular imprints. Low-grade DCIS, lobular, and special type
      cancers account for most such lesions. The results of the current study also
      demonstrated significant variations in the accuracy of CIC in microcalcifications
      versus parenchymal lesions. In particular, the results of acellular imprints are
      analogous to benign CIC findings for microcalcifications but not in parenchymal
      lesions. CONCLUSIONS: The current study may be the largest prospective series on
      CIC to date, and the only direct comparison of its results for
      microcalcifications versus parenchymal lesions. Breast CIC is a reliable
      predictor of core histology. The information this study provides can be used to
      clinical advantage.

PMID- 16634071
TI  - Fine-needle aspiration biopsy of hepatic lesions: computerized tomographic-guided
      versus endoscopic ultrasound-guided FNA.
AB  - BACKGROUND: Computerized tomographic (CT)-guided fine-needle aspiration (FNA)
      cytology is a well-established tool in the diagnosis of hepatic lesions.
      Endoscopic ultrasound-guided FNA (EUS-FNA), developed recently and used
      predominantly in evaluating mediastinal and pancreatic lesions, provides access
      to a significant portion of the liver and to perihepatic structures not readily
      accessible by a percutaneous approach. METHODS: A recent experience (1997-2002)
      with CT-guided FNA of liver lesions at the University of Alabama Birmingham (UAB)
      was compared with the first 2.5 years of EUS-FNA experience (2000-2002). Cases
      were identified using a SNOMED search and all reports and cytologic slides were
      retrieved for review. RESULTS: In 6 years, 34 percutaneous CT-FNA liver biopsies
      were performed at UAB; in approximately 2.5 years, 16 EUS-FNA liver biopsies were
      done. In both groups the primary clinical indication was suspected metastatic
      carcinoma (CT, 41% of cases vs. EUS, 56%). The 2 techniques yielded a similar
      range of benign, atypical, and malignant diagnoses (CT: 26%, 18%, and 56% vs.
      EUS: 19%, 25%, and 56%). Because of the clinical setting in which EUS-FNA is
      usually performed, a much narrower range of neoplasms was sampled by EUS-FNA.
      Benign gastrointestinal epithelial cells were identified in 60% of the EUS-FNA
      specimens. CONCLUSIONS: Early experience suggests EUS-FNA is comparable to CT-FNA
      in terms of diagnostic utility for hepatic lesions. Anatomy limits EUS-FNA to
      only a fraction of the hepatic parenchyma, but that fraction includes the hilum
      and left lobe of the liver and the proximal biliary tract. The gallbladder,
      extrahepatic biliary system, and perihilar lymph nodes are readily accessible.
      Proximate high-resolution ultrasound imaging and cytopathologist involvement in
      the EUS-FNA process are further advantages. Awareness of artifacts inherent in
      EUS-FNA sampling (i.e., gut epithelial cells) can minimize a potential diagnostic
      pitfall.

PMID- 16634072
TI  - Clinical and histological healing pattern of peri-implantitis lesions following
      non-surgical treatment with an Er:YAG laser.
AB  - BACKGROUND AND OBJECTIVES: The aim of the present study was to assess clinical
      and histo-pathological healing pattern of peri-implantitis lesions following non
      surgical treatment with an Er:YAG laser (ERL). STUDY DESIGN/MATERIALS AND
      METHODS: Twelve patients suffering from peri-implantitis (n = 12 implants)
      received a single episode of non-surgical instrumentation using ERL (12.7 J/cm2).
      Assessment of clinical parameters (plaque index (PI), bleeding on probing (BOP),
      probing pocket depth, gingival recession (GR), and clinical attachment level
      (CAL)), surgical defect examination, and histo-pathological examination of peri
      implant tissue biopsies was performed after 1, 3, 6, 9, 12, and 24 months.
      RESULTS: All patients exhibited improvements of all clinical parameters
      investigated. However, histo-pathological examination of tissue biopsies revealed
      a mixed chronic inflammatory cell infiltrate (macrophages, lymphocytes, and
      plasma cells) which seemed to be encapsulated by deposition of irregular bundles
      of fibrous connective tissue showing increased proliferation of vascular
      structures. CONCLUSION: It was concluded that a single course of non-surgical
      treatment of peri-implantitis using ERL may not be sufficient for the maintenance
      of failing implants.

PMID- 16634073
TI  - PDT-associated host response and its role in the therapy outcome.
AB  - BACKGROUND AND OBJECTIVES: The outcome of the treatment of solid tumors by
      photodynamic therapy (PDT) is critically dependent on the contribution from the
      host. This host response is provoked by the rapidly induced massive tumor tissue
      injury delivered by PDT that is experienced as a local trauma threatening the
      integrity and homeostasis at the affected site. STUDY DESIGN/MATERIALS AND
      METHODS: Mouse tumor models were extensively employed in pre-clinical studies
      investigating various aspects of host-tumor interaction following PDT, but
      important input was also derived from clinical data. RESULTS: The recognition of
      this PDT-inflicted insult by innate immune sensors detecting danger signals from
      the distressed/altered tumor tissue, triggers host-protecting responses
      dominantly manifested as acute inflammation that are elicited and orchestrated by
      the innate immune system. To secure the affected PDT-targeted site, the
      inflammatory reaction attacks tumor vasculature and then neutralizes the focal
      source of danger signals by eliminating the injured tumor cells. CONCLUSION: The
      provoked highly intensified phagocytosis of dead tumor cells occurring in the
      context of a vigorous innate immune reaction emerges as a key factor responsible
      for the development of tumor antigen-specific adaptive immune response that
      contributes to the eradication of PDT-treated cancers.

PMID- 16634074
TI  - Effects of argon laser irradiation on polar excitations in frog sciatic nerve.
AB  - BACKGROUND AND OBJECTIVES: Since the mechanisms underlying the effects of low
      power laser irradiation on the nervous system remain unclear, we examined whether
      such irradiation can influence ionic channels of the nerve membrane using the law
      of polar excitation in isolated frog sciatic nerve. STUDY DESIGN/MATERIALS AND
      METHODS: Using 43 frogs (Xenopus laevis), nerve preparations were stimulated at
      0.5/second using a 10-millisecond pulse at supramaximal intensity. Ar+ laser
      irradiation (457, 488, 514 nm; 50, 75, 100 mW) was applied for 30 minutes to the
      portion between the anode and cathode stimulating electrodes. RESULTS AND
      CONCLUSIONS: Ar+ laser irradiations (457, 488 nm; 50 mW) blocked the generation
      of anode-break-excitation, rather than cathode-make-excitation. Such a selective
      effect occurred when applying a blocker of hyperpolarization-activated cation
      current (Ih) channel, ZD7288. Ar+ laser irradiation may influence Na+ channels in
      addition to Ih channels.

PMID- 16634075
TI  - Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium
      (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5
      ALA-induced protoporphyrin IX.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) uses a photosensitizer
      activated by light, in an oxygen-rich environment, to destroy malignant tumors.
      Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the
      photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX
      (PpIX). In some studies the concentrations of photosensitizer in blood, and
      occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these
      individual studies were pooled and analyzed. This is the first published review
      to compare head-to-head the PK of Photofrin and Photochlor. STUDY
      DESIGN/MATERIALS AND METHODS: Blood and tissue specimens were obtained from
      patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and
      PpIX were measured using fluorescence analysis. A non-linear mixed effects
      modeling approach was used to analyze the PK data for Photochlor (up to 4 days
      post-infusion; two-compartment model) and a simpler multipatient-data-pooling
      approach was used to model PK data for both Photofrin and Photochlor (at least
      150 days post-infusion; three-compartment models). Physiological parameters were
      standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to
      facilitate comparisons between Photofrin and Photochlor. RESULTS: Serum
      concentration-time profiles obtained for Photofrin and Photochlor showed long
      circulating half-lives, where both sensitizers could be found more than 3 months
      after intravenous infusion; however, estimated plasma clearances (standard man)
      were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2
      ml/hour). Volumes of distribution of the central compartment (standard man) for
      both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively)
      of plasma volume, implying that both photosensitizers are almost 100% bound to
      serum components. Circulating levels of PpIX were generally quite low, falling
      below the level of instrument sensitivity within a few days after topical
      application of 5-ALA. CONCLUSION: We have modeled the PK of Photochlor and
      Photofrin. PK parameter estimates may, in part, explain the relatively long skin
      photosensitivity attributed to Photofrin but not Photochlor. Due to the potential
      impact and limited experimental PK data in the PDT field further clinical studies
      of photosensitizer kinetics in tumor and normal tissues are warranted.

PMID- 16634076
TI  - Plasma exchange therapy for victims of envenomation: is this reasonable?

PMID- 16634077
TI  - Mechanisms underlying the inability to induce area CA1 LTP in the mouse after
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a significant health issue that often causes
      enduring cognitive deficits, in particular memory dysfunction. The hippocampus, a
      structure crucial in learning and memory, is frequently damaged during TBI. Since
      long-term potentiation (LTP) is the leading cellular model underlying learning
      and memory, this study was undertaken to examine how injury affects area CA1 LTP
      in mice using lateral fluid percussion injury (FPI). Brain slices derived from
      FPI animals demonstrated an inability to induce LTP in area CA1 7 days
      postinjury. However, area CA1 long-term depression could be induced in neurons 7
      days postinjury, demonstrating that some forms of synaptic plasticity can still
      be elicited. Using a multi-disciplined approach, potential mechanisms underlying
      the inability to induce and maintain area CA1 LTP were investigated. This study
      demonstrates that injury leads to significantly smaller N-methyl-D-aspartate
      potentials and glutamate-induced excitatory currents, increased dendritic spine
      size, and decreased expression of alpha-calcium calmodulin kinase II. These
      findings may underlie the injury-induced lack of LTP and thus, contribute to
      cognitive impairments often associated with TBI. Furthermore, these results
      provide attractive sites for potential therapeutic intervention directed toward
      alleviating the devastating consequences of human TBI.

PMID- 16634078
TI  - Developmental toxicity evaluation of berberine in rats and mice.
AB  - BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health
      related products. It is a component of goldenseal, an herbal supplement.
      Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in
      rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed
      to timed-mated Sprague-Dawley (CD) rats (0, 3,625, 7,250, or 14,500 ppm; on
      gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3,500, 5,250, or
      7,000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1,313 mg/kg/day
      (rats) and 0, 569, 841, and 1,155 mg/kg/day (mice). RESULTS: There were no
      maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL),
      based on reduced maternal weight gain, was 7,250 ppm. The rat developmental
      toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In
      the mouse study, equivocal maternal and developmental toxicity LOAELs were 5,250
      ppm. Due to scattering of feed in the high dose groups, a gavage study at 1,000
      mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not
      fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7,250
      ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL
      was raised to 1,000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of
      the treated females died. Surviving animals had increased relative water intake,
      and average fetal body weight per litter decreased 5-6% with no change in live
      litter size. The maternal toxicity LOAEL remained at 5,250 ppm (841 mg/kg/day)
      BCD, based on increased water consumption. The developmental toxicity LOAEL was
      raised to 1,000 mg/kg/day BCD based on decreased fetal body weight.

PMID- 16634079
TI  - Mental health and related disability among workers: a population-based study.
AB  - BACKGROUND: In past decades, the nature of work has undergone significant changes
      including increased psychological demands and job instability. A stressful
      psychosocial work environment has been shown to have adverse effects on workers'
      mental and physical health. This goal of this study is to estimate the prevalence
      of psychiatric syndromes and related disability in a population-based sample of
      employed adults and investigate associations between psychiatric syndromes and
      related disability. METHODS: A random-digit dial provincial wide mental health
      survey was conducted in Alberta, Canada (n = 5,383). The telephone interview
      included the Mini International Neuropsychiatric Interview (MINI) and the World
      Health Organization's Disability Assessment Schedule (WHO-DAS-II). In this
      analysis, participants who were currently employed were included (n = 4,149).
      RESULTS: In this population, 6.2% had had at least one MINI-defined psychiatric
      diagnosis with clinically significant interference. Without consideration of the
      clinical interference criterion, the prevalence of psychiatric syndromes was
      higher (33.5%). Psychiatric syndromes were strongly associated with disability. A
      dose-response relationship between the number of diagnoses and disability was
      found. CONCLUSIONS: Interventional strategies in the workplace should focus on
      mental disorders at both the clinical and sub-clinical levels.

PMID- 16634080
TI  - The Mine Safety and Health Administration's criterion threshold value policy
      increases miners' risk of pneumoconiosis.
AB  - BACKGROUND: The Mine Safety and Health Administration (MSHA) proposes to issue
      citations for non-compliance with the exposure limit for respirable coal mine
      dust when measured exposure exceeds the exposure limit with a "high degree of
      confidence." This criterion threshold value (CTV) is derived from the sampling
      and analytical error of the measurement method. CONCEPTUAL FRAMEWORK: This policy
      is based on a combination of statistical and legal reasoning: the one-tailed 95%
      confidence limit of the sampling method, the apparent principle of due process
      and a standard of proof analogous to "beyond a reasonable doubt." CRITIQUE: This
      policy raises the effective exposure limit, it is contrary to the precautionary
      principle, it is not a fair sharing of the burden of uncertainty, and it employs
      an inappropriate standard of proof. Its own advisory committee and NIOSH have
      advised against this policy. For longwall mining sections, it results in a
      failure to issue citations for approximately 36% of the measured values that
      exceed the statutory exposure limit. DISCUSSION: Citations for non-compliance
      with the respirable dust standard should be issued for any measure exposure that
      exceeds the exposure limit.

PMID- 16634081
TI  - Myosin light chain kinase colocalizes with nonmuscle myosin IIB in myofibril
      precursors and sarcomeric Z-lines of cardiomyocytes.
AB  - Myosin light chain kinase (MLCK) is a key regulator of various forms of cell
      motility involving actin and myosin II. MLCK is widely present in vertebrate
      tissues including the myocardium. However, the role of MLCK in cardiomyocyte
      function is not known. Previous attempts to gain insight into possible roles and
      identify potential molecular partners were disappointing and equivocal due to
      cross reactivity of early antibodies with striated muscle MLCK, which has a
      different genetic locus and a divergent amino acid sequence from the above
      mentioned enzyme. Using an immunofluorescence approach and a panel of antibodies
      directed against MLCK, cytoskeletal, and sarcomeric proteins, we localized MLCK
      to myofibril precursors and Z-lines of sarcomeres in embryonic and adult
      cardiomyocytes. The same structures contained nonmuscle myosin IIB implicating
      this protein as a possible target of MLCK. Our results suggest a role for MLCK in
      cardiomyocyte differentiation and contraction through regulation of nonmuscle
      myosin IIB.

PMID- 16634082
TI  - Sensitivity of alveolar macrophages to substrate mechanical and adhesive
      properties.
AB  - In order to understand the sensitivity of alveolar macrophages (AMs) to substrate
      properties, we have developed a new model of macrophages cultured on substrates
      of increasing Young's modulus: (i) a monolayer of alveolar epithelial cells
      representing the supple (approximately 0.1 kPa) physiological substrate, (ii)
      polyacrylamide gels with two concentrations of bis-acrylamide representing low
      and high intermediate stiffness (respectively 40 kPa and 160 kPa) and, (iii) a
      highly rigid surface of plastic or glass (respectively 3 MPa and 70 MPa), the two
      latter being or not functionalized with type I-collagen. The macrophage response
      was studied through their shape (characterized by 3D-reconstructions of F-actin
      structure) and their cytoskeletal stiffness (estimated by transient twisting of
      magnetic RGD-coated beads and corrected for actual bead immersion). Macrophage
      shape dramatically changed from rounded to flattened as substrate stiffness
      increased from soft ((i) and (ii)) to rigid (iii) substrates, indicating a net
      sensitivity of alveolar macrophages to substrate stiffness but without generating
      F-actin stress fibers. Macrophage stiffness was also increased by large substrate
      stiffness increase but this increase was not due to an increase in internal
      tension assessed by the negligible effect of a F-actin depolymerizing drug
      (cytochalasine D) on bead twisting. The mechanical sensitivity of AMs could be
      partly explained by an idealized numerical model describing how low cell height
      enhances the substrate-stiffness-dependence of the apparent (measured) AM
      stiffness. Altogether, these results suggest that macrophages are able to probe
      their physical environment but the mechanosensitive mechanism behind appears
      quite different from tissue cells, since it occurs at no significant cell-scale
      prestress, shape changes through minimal actin remodeling and finally an AMs
      stiffness not affected by the loss in F-actin integrity.

PMID- 16634083
TI  - Maximum intraoperative elongation of the rat sciatic nerve with tissue expander:
      functional, neurophysiological, and histological assessment.
AB  - The purpose of this study was to assess the maximum rapid intraoperative
      elongation of the rat sciatic nerve with the use of tissue expander, and its
      possible functional recovery. One hundred and eight rats were divided into five
      groups, and their right sciatic nerves were expanded with a 10-cc, 12-cc, 14-cc,
      16-cc, and 18-cc expander, respectively, for 1 h. The functional recovery of the
      nerve was assessed at intervals up to 3 months, using the sciatic function index
      (SFI), neurophysiological indices, and histology. The maximum intraoperative
      elongation was observed in group IV (16-cc volume of tissue expander), at about
      23.83%. SFI decreased between the first and seventh postoperative days, but
      gradually recovered, reaching preoperative values in all groups according to the
      formulas of De Medinaceli et al. (Exp. Neurol. 77:634-643, 1982) and Bain et al.
      (Plast. Reconstr. Surg. 83:129-136, 1989). Latency and motor conduction velocity
      demonstrated deterioration after expansion, which peaked after surgery. Recovery
      was gradually completed by the end of the experiment. The histological findings
      indicated minor aberrations immediately after expansion and maximal demyelination
      with axonal disruption on day 15. The reparative process started by day 30 and
      continued until day 90, when almost no histological changes were observed. In
      conclusion, intraoperative nerve expansion successfully elongates the rat sciatic
      nerve up to 23.83%. But it causes functional and morphological abnormalities,
      which are of moderate to severe degree, are of short duration, and are
      reversible. Intraoperative nerve expansion might be a valuable solution in the
      treatment of short nerve gaps, but its clinical application still needs to be
      evaluated.

PMID- 16634084
TI  - Long-term results of primary repair of brachial plexus lesions in children.
AB  - The results of brachial plexus reconstruction in adults are poor, despite the
      sophistication of the various methods used. However, the same methods used in
      neonates after obstetrical brachial plexus injury will give far better results
      because of the shorter distance, stronger potential of regeneration, and capacity
      of brain adaptation. Complete paralyses, associated root ruptures, and avulsions
      are very severe, and the end results cannot be evaluated before the end of
      growth. Although the end results show that the shoulder and elbow do not do as
      well as in upper-type lesions, the results at the level of the hand are
      encouraging, showing 75% with useful function after 8 years, even in patients
      with avulsion injuries of the lower roots. These results demonstrate the value of
      the early exploration and repair of the obstetric plexus. We also review our
      series of traumatic brachial plexus palsy in children. The results are poorer
      than in neonates, where may be related, in part, to a greater percentage of
      associated lesions in these patients.

PMID- 16634085
TI  - Ontogeny and homology of the claustra in otophysan Ostariophysi (Teleostei).
AB  - We studied the ontogeny of the claustrum comparatively in representatives of all
      otophysan subgroups. The claustrum of cypriniforms has a cartilaginous precursor,
      the claustral cartilage, which subsequently ossifies perichondrally at its
      anterior face and develops an extensive lamina of membrane bone. The membrane
      bone component of the claustrum and its close association with the atrium sinus
      imparis, a perilymphatic space of the Weberian apparatus, are both synapomorphies
      of cypriniforms. The characiform claustrum is not preformed in cartilage and
      originates as a membrane bone ossification, a putative synapomorphy of that
      taxon. Among siluriforms, the claustrum is present only in more basal groups and
      originates as an elongate cartilage that ossifies in a characteristic
      ventrodorsal direction, possibly a synapomorphy of catfishes. Gymnotiforms lack
      the claustral cartilage and claustrum. We review all previous hypothesis of
      claustrum homology in light of the above findings and conclude that the most
      plausible hypothesis is the one originally proposed by Bloch ([1900] Jen Z Naturw
      34:1-64) that claustra are homologs of the supradorsals of the first vertebra.

PMID- 16634086
TI  - Morphology of the gular valve of the Nile crocodile, Crocodylus niloticus
      (Laurenti, 1768).
AB  - The morphology of the gular valve of the Nile crocodile was studied on the heads
      of eight 2.5-3-year-old commercially raised Nile crocodiles (Crocodylus
      niloticus). A description of the macroscopic and microscopic features of the
      gular valve is presented and the results are compared with published information
      on this species and other Crocodylia. The histological features are supplemented
      by information supplied by scanning electron microscopy (SEM). Anatomically, the
      dorsal and ventral components of the gular valve in the Nile crocodile form an
      efficient seal that effectively separates the oral and pharyngeal cavities
      consistent with the natural behavior and feeding habits of this animal. The gular
      valve is more complex in nature than superficial observations would suggest, with
      the dorsal and ventral folds being complemented by a series of smaller folds,
      particularly at the lateral fringes of the valve. Histologically, the surface
      epithelium of the valve demonstrates a transition from the typical stratified
      squamous epithelium of the oral cavity to that of the respiratory epithelium
      lining the pharyngeal cavity. The respiratory epithelium is characterized by the
      presence of ciliated cells and goblet cells and is accompanied by the appearance
      of large mucus-secreting glands in the underlying connective tissue. The
      transition between the two epithelial types is marked by the presence of a
      relatively prominent region where the stratified squamous epithelial cells
      undergo a gradual transformation into the typical elements of a respiratory
      epithelium. SEM graphically illustrated the extent of ciliation on both
      components of the gular valve as well as clearly defining the transition zones
      between the various types of surface epithelium present. No structures resembling
      taste receptors were observed in the mucosa of the gular valve.

PMID- 16634087
TI  - A transmembrane helix-bundle from G-protein coupled receptor CB2: biosynthesis,
      purification, and NMR characterization.
AB  - The cannabinoid receptor subtype 2 (CB2) is a member of the G-protein coupled
      receptor (GPCR) superfamily. As the relationship between structure and function
      for this receptor remains poorly understood, the present study was undertaken to
      characterize the structure of a segment including the first and second
      transmembrane helix (TM1 and TM2) domains of CB2. To accomplish this, a
      transmembrane double-helix bundle from this region was expressed, purified, and
      characterized by NMR. Milligrams of this hydrophobic fragment of the receptor
      were biosynthesized using a fusion protein overexpression strategy and purified
      by affinity chromatography combined with reverse phase HPLC. Chemical and
      enzymatic cleavage methods were implemented to remove the fusion tag. The
      resultant recombinant protein samples were analyzed and confirmed by HPLC, mass
      spectrometry, and circular dichroism (CD). The CD analyses of HPLC-purified
      protein in solution and in DPC micelle preparations suggested predominant alpha
      helical structures under both conditions. The 13C/15N double-labeled protein
      CB2(27-101) was further verified and analyzed by NMR spectroscopy. Sequential
      assignment was accomplished for more than 80% of residues. The 15N HSQC NMR
      results show a clear chemical shift dispersion of the amide nitrogen-proton
      correlation indicative of a pure double-labeled polypeptide molecule. The results
      suggest that this method is capable of generating transmembrane helical bundles
      from GPCRs in quantity and purity sufficient for NMR and other biophysical
      studies. Therefore, the biosynthesis of GPCR transmembrane helix bundles
      represents a satisfactory alternative strategy to obtain and assemble NMR
      structures from recombinant "building blocks."

PMID- 16634088
TI  - The neural system that mediates familiarity memory.
AB  - In recognition memory tests, feelings of familiarity for stimuli vary in
      strength. Increasing levels of felt familiarity should modulate activity in brain
      structures that mediate familiarity memory. We used this expectation to identify
      the neural system that underlies scene familiarity memory. Normal subjects
      studied pictures of scenes and 2 days later while undergoing event-related
      functional magnetic resonance imaging (fMRI) rated old and new pictures as novel,
      slightly familiar, moderately familiar, very familiar, or recollected, although
      they were specifically instructed not to try and recollect. Familiarity strength
      was, therefore, judged as absent (misses) or present at three levels of
      increasing strength. A parametric analysis showed that, as perceived strength of
      familiarity increased activity in the perirhinal cortex, insula and left superior
      temporal cortex declined linearly whereas activity in the left dorsomedial
      thalamus, left ventrolateral and anteromedial frontal cortex, posterior cingulate
      cortex, and left parietal neocortex increased linearly. Hippocampal activity was
      not modulated linearly or quadratically by changes in familiarity strength.
      Recollection activated the hippocampus, and left anterior and inferolateral
      frontal and parietal cortices more than strong familiarity. In contrast, no brain
      region that was unaffected by recollection (relative to misses and correct
      rejections) was modulated by variations in familiarity strength. The implications
      of these findings for the functional and neural bases of familiarity and
      recollection are considered.

PMID- 16634089
TI  - Volume and process of care in high-risk cancer surgery.
AB  - BACKGROUND: Although relations between procedure volume and operative mortality
      are well established for high-risk cancer operations, differences in clinical
      practice between high-volume and low-volume centers are not well understood. The
      current study was conducted to examine relations between hospital volume, process
      of care, and operative mortality in cancer surgery. METHODS: Using the Medicare
      claims database (2000-2002), we identified all patients undergoing major
      resections for lung, esophageal, gastric, liver, or pancreatic cancer (n=71,558).
      Preoperative, intraoperative, and postoperative processes of care potentially
      related to operative mortality were identified from inpatient, outpatient, and
      physician claims files using appropriate International Classification of Diseases
      -Clinical Modification (ICD-9) and Current Procedural Terminology (CPT) codes. We
      then assessed variation in the use of each process according to hospital volume,
      adjusting for patient characteristics and procedure type. Study Participants were
      US Medicare patients. The main outcome measure was specific processes of care.
      RESULTS: Relative to those at low-volume centers (lowest 20th by volume),
      patients at high-volume hospitals (highest 20th) were significantly more likely
      to undergo stress tests (odds ratio [OR]: 1.51, 95% confidence interval [CI]:
      1.21-1.87), but not other preoperative imaging tests. They were more likely to
      see medical or radiation oncologists (OR: 1.37, 95% CI: 1.16-1.62), but not other
      specialists, preoperatively. Although blood transfusions and use of epidural pain
      management did not vary significantly by volume, patients at high-volume
      hospitals had significantly longer operations and were more likely to receive
      perioperative invasive monitoring (OR: 2.56, 95% CI: 1.82-3.60). Differences in
      measurable processes of care did not explain volume-related differences in
      operative mortality to any significant degree. CONCLUSIONS: Although high-volume
      and low-volume hospitals differ with regard to many aspects of perioperative
      care, mechanisms underlying volume-outcome relations in high-risk cancer surgery
      remain to be identified.

PMID- 16634090
TI  - Histological changes in the liver of fetuses of alcohol-treated pregnant rats.
AB  - In this study, immunolocalization of tenascin (TN), type IV collagen and
      histopathological changes in the liver of fetuses of pregnant Wistar albino rats
      treated with two doses of alcohol (1 and 5 g kg(-1) day(-1)) were determined. The
      samples of liver obtained from fetuses of rats on day 21 of gestation were
      evaluated morphologically and fixed for histology and immunohistochemistry. The
      sections stained with H&E and peroxidase-antiperoxidase (PAP) method for TN and
      type IV collagen were evaluated and immunohistochemical staining results were
      examined by the intensity of labelling. Statistical evaluation of data showed
      that there were no differences in liver weights between the control and calorie
      control groups; but some differences in relative liver weight between the control
      and alcohol treatment groups were determined. The changes in the liver histology
      such as degeneration of the cytoplasm of hepatocytes and increases in the number
      of megakaryocytes were seen in the fetuses of groups receiving alcohol during
      pregnancy. Increases in the immunolocalization of TN and type IV collagen in the
      liver of fetuses of alcohol-receiving rats were also found.

PMID- 16634091
TI  - Oxidative stress and enzymic-non-enzymic antioxidant responses in children with
      acute pneumonia.
AB  - In this article, oxidative stress and enzymic-non-enzymic antioxidants status
      were investigated in children with acute pneumonia. Our study included 28
      children with acute pneumonia and 29 control subjects. The age ranged from 2 to
      11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study
      and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced
      glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase
      (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase
      (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There
      was a statistically significant difference between the groups for all parameters
      except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were
      higher in the study group than those of the control group. However, SOD, GPx,
      beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the
      study group compared with the control group. All antioxidant vitamin activities
      were decreased in children with acute pneumonia. Our study demonstrated that
      oxidative stress was increased whereas enzymic and non-enzymic antioxidant
      activities were significantly decreased in children with acute pneumonia.

PMID- 16634092
TI  - Antioxidative and anti-diabetic effects of amaranth (Amaranthus esculantus) in
      streptozotocin-induced diabetic rats.
AB  - The anti-diabetic and antioxidative effect of amaranth grain (AG) and its oil
      fraction (AO) was studied in streptozotocin-induced diabetic rats. Male Sprague
      Dawley rats were divided into four groups after induction of STZ-diabetes: normal
      control; diabetic control; diabetic-AG supplement (500 g kg(-1) diet); diabetic
      AO supplement (100 g kg(-1) diet) and fed experimental diets for 3 weeks. Serum
      glucose, insulin, activities of serum marker enzymes of liver function and liver
      cytosolic antioxidant enzymes were measured. The AG and AO supplement
      significantly decreased the serum glucose and increased serum insulin level in
      diabetic rats. Serum concentration of liver function marker enzymes, GOT and GPT,
      were also normalized by AG and AO treatment in diabetic rats. Liver cytosolic SOD
      and GSH-reductase activities were significantly increased, and catalase,
      peroxidase and GSH-Px activities were decreased in diabetic rats. AG and AO
      supplement reverted the antioxidant enzyme activities to near normal values.
      Hepatic lipid peroxide product was significantly higher, and GSH content was
      decreased in diabetic rats. However, AG and AO supplement normalized these
      values. Our data suggest that AG and AO supplement, as an antioxidant therapy,
      may be beneficial for correcting hyperglycaemia and preventing diabetic
      complications.

PMID- 16634093
TI  - Evaluation of neuronal damage following hypoxic-ischaemic brain injury in acute
      and early chronic periods in neonatal rats.
AB  - This study was undertaken to investigate the effects of neonatal cerebral hypoxic
      ischaemic brain injury (HIBI) in acute and early chronic phases in the rat. HIBI
      was induced in 7-day-old rat pups by ligation of the right common carotid and
      then the pups were exposed to 1 h of hypoxia in 8% oxygen. They were divided into
      two groups: 1-day (acute phase, in the first 24 h) and 5-day (early chronic
      phase, 120 h). Neuropathological evaluation was performed using the hippocampus,
      cerebral cortex and basal ganglia on the coronal plane. The following values were
      obtained: (i) the ratio of the infarcted area; (ii) hemispheric
      atrophy/asymmetry; (iii) patchy lesions confined to the thalamus, caudate and
      putamen; (iv) the ratio of damaged neurons to all neurons; and (v) the percentage
      of apoptotic neurons relative to the total neurons in all brain areas. HIBI
      induced global cerebral damage and cellular damage findings did not significantly
      differ between the two groups. However, they showed a tendency to
      recover/deteriorate in both acute and early chronic phases. The ratio of ipsi-
      and contra-lateral hemisphere infarct areas (20.7 and 15.7% vs. 40.1 and 26.7%,
      respectively), basal ganglia patchy lesion ratio (27.5 vs. 36.7%) and hemispheric
      atrophy/asymmetry (92.4 vs. 84.7%) were found to be lower in the rat pups in the
      chronic phase than those in the acute phase. In contrast, increases in the ratio
      of damaged neurons (16.7 vs. 13.3% in the cerebral and dorsal hippocampus,
      respectively) and in the ratio of apoptotic neurons (ipsi-lateral: 18 vs. 6%;
      contra lateral hemispheres: 3.5 vs. 1.7%, respectively) were recorded. It is
      concluded that cellular damage tends to deteriorate (damaged and apoptotic
      neurons) while global damage (cerebral infarct and patchy damage) improves with
      the progression of HIBI. However, further studies are needed in order to
      elucidate this process.

PMID- 16634094
TI  - Apolipoprotein B gene variants are involved in the determination of blood glucose
      and lipid levels in patients with non-insulin dependent diabetes mellitus.
AB  - We have examined the frequency of the EcoRI, XbaI and MspI RFLPs of the
      apolipoprotein B (apo B) gene in 110 type 2 diabetic patients and 91 healthy
      control subjects in order to ascertain whether variation in this gene may
      influence the development of non-insulin dependent diabetes mellitus (type 2
      diabetes). Serum lipids including total-cholesterol (T-Chol), triacylglycerol
      (TAG), apolipoprotein E (apo E), apolipoprotein AI (apo AI), apolipoprotein B and
      lipoprotein (a) (Lp(a)) were analysed. Genomic DNA was extracted and the apo B
      polymorphic regions amplified by the polymerase chain reaction. Regions carrying
      EcoRI, XbaI, and MspI restriction sites present in the apo B gene were amplified
      and digested separately by the respective enzymes. No significant difference for
      genotypic frequencies was observed for the EcoRI, XbaI and MspI restriction sites
      in type 2 diabetic patients as compared to controls. Type 2 diabetic patients and
      controls with EcoRI +/+ and XbaI +/+ genotypes had higher apo E levels. The MspI
      +/+ genotype is more frequent in the patient and control groups with elevated T
      Chol. Furthermore, the EcoRI -/-, XbaI -/-, and MspI +/+ genotypes were found to
      be significantly more frequent in type 2 diabetic patients with higher blood
      glucose levels. This study identifies the apo B gene polymorphisms in modulating
      plasma lipid/lipoprotein and glucose levels in patients with type 2 diabetes.

PMID- 16634095
TI  - Ab initio calculations of intramolecular parameters for a class of arylamide
      polymers.
AB  - Using DFT methods, we have determined intramolecular parameters for an important
      class of arylamide polymers displaying antimicrobial and anticoagulant inhibitory
      properties. A strong link has been established between these functions and the
      conformation that the polymers adopt in solution and at lipid bilayer interfaces.
      Thus, it is imperative for molecular dynamics simulations designed to probe the
      conformational behavior of these systems to accurately describe the torsional
      degrees of freedom. Standard force fields were shown to be deficient in this
      respect. Therefore, we have computed the relevant torsional energy profiles using
      a series of constrained geometry optimizations. We have also determined
      electrostatic parameters using our results in combination with standard RESP
      charge optimization. Force constants for bond and angle potentials were
      calculated by iteratively matching quantum and classical normal modes via a Monte
      Carlo scheme. The resulting new set of parameters accurately described the
      conformation and dynamical behavior of the arylamide polymers.

PMID- 16634096
TI  - Smoking affects treatment outcome in patients with advanced nonsmall cell lung
      cancer.
AB  - BACKGROUND: The purpose of the current study was to determine whether smoking
      during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer
      (NSCLC) affects treatment outcome. METHODS: The authors reviewed the medical
      records of patients with NSCLC (AJCC Stage III or IV) who were treated with
      frontline chemotherapy or chemoradiation therapy at the University of Texas M. D.
      Anderson Cancer Center between January 1993 and December 2002. Treatment type,
      response, progression-free survival, and overall survival (OS) were correlated
      with patient demographic characteristics, clinical features, and smoking habits
      at the time of diagnosis and during therapy. RESULTS: Of 1370 patients who were
      eligible for analysis, 497 received chemoradiation therapy and 873 received
      chemotherapy. In the chemoradiation group, 6% of patients were never-smokers, 45%
      were former smokers, and 49% were current smokers. Multivariate analysis
      demonstrated no prognostic effect of smoking status on treatment response or OS
      rates in the chemoradiation therapy group. In the chemotherapy group, 16% of
      patients were never-smokers, 42% were former smokers, and 42% were current
      smokers; 20% of patients continued to smoke during therapy. Never-smokers had
      higher response rates (19% vs. 8% vs. 12%; P=.004) and lower rates of progressive
      disease (49% vs. 65% vs. 66%; P=.002) than former and current smokers,
      respectively. The OS rates were found to be higher among never-smokers (P<0001),
      women (P=.002), and those with a better Eastern Cooperative Oncology Group (ECOG)
      performance status (P<.0001). The multivariate Cox model indicated that with
      adjustment for age, gender, stage of disease, and ECOG performance status, the
      hazard ratio was 1.47 for former smokers (P=.003) and 1.55 for current smokers
      (P=.0004). Active smoking during therapy did not appear to impact outcome.
      CONCLUSIONS: Never-smokers were found to have an improved outcome over smokers
      when treated with chemotherapy.

PMID- 16634097
TI  - Patterns and predictors of mammography utilization among breast cancer survivors.
AB  - BACKGROUND: Improvements in cancer detection and treatment have resulted in
      increasing numbers of breast cancer survivors. Information regarding the use of
      mammography by breast cancer survivors is limited. METHODS: The use of
      surveillance mammography was examined over a 5-year period in a retrospective
      cohort of women age>or=55 years who were diagnosed with incident primary breast
      cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated
      health systems. RESULTS: Of the 797 women included in the study, 80% (n=636)
      underwent mammograms during the first year after treatment for breast cancer. The
      percentage of women having mammograms during each yearly period decreased
      significantly over time. In multivariable analyses, older women with comorbid
      illnesses or those with late-stage disease were less likely to undergo
      mammograms, whereas those who underwent breast-conserving therapy (adjusted odds
      ratio [OR] of 1.38 [95% confidence interval (95% CI), 1.09-1.75]) were more
      likely to have mammograms. Women who had outpatient visits with a gynecologist
      (adjusted OR of 3.49 [95% CI, 2.55-4.79]), or a primary care physician (adjusted
      OR of 2.21 [95% CI, 1.73-2.82]) during the year were more likely to undergo
      mammograms in that year. CONCLUSIONS: The use of mammography among breast cancer
      survivors declines over time. Efforts are needed to increase awareness among
      healthcare providers and breast cancer survivors of the value of follow-up
      mammography. The current findings highlight the importance of maintaining ongoing
      contact with primary care physicians and gynecologists.

PMID- 16634098
TI  - Regioselective glucosylation of aromatic compounds: screening of a recombinant
      glycosyltransferase library to identify biocatalysts.

PMID- 16634099
TI  - An approach to prepare membrane proteins for single-molecule imaging.

PMID- 16634100
TI  - Introduction of 2,2,2-trichloroethyl-protected sulfates into monosaccharides with
      a sulfuryl imidazolium salt and application to the synthesis of sulfated
      carbohydrates.

PMID- 16634101
TI  - A new class of biochemically degradable, stimulus-responsive triblock copolymer
      gelators.

PMID- 16634102
TI  - Titanium-salan-catalyzed asymmetric epoxidation with aqueous hydrogen peroxide as
      the oxidant.

PMID- 16634103
TI  - Reversible sulfurization-desulfurization of tungsten bis(dithiolene) complexes.

PMID- 16634104
TI  - Cationic terminal borylene complexes: Interconversion of amino and alkoxy
      borylenes by an unprecedented Meerwein-Ponndorf hydride transfer.

PMID- 16634105
TI  - Controlling RNA digestion by RNase H with a light-activated DNA hairpin.

PMID- 16634106
TI  - Total synthesis of abyssomicin C and atrop-abyssomicin C.

PMID- 16634107
TI  - Design and synthesis of simple macrocycles active against vancomycin-resistant
      enterococci (VRE).
AB  - 16-membered meta,para-cyclophanes mimicking the vancomycin binding pocket (D-O-E
      ring) were designed and synthesized. The structural key features of these biaryl
      ether containing macrocycles are (1) the presence of beta-amino-alpha-hydroxy
      acid or alpha,beta-diamino acid as the C-terminal component of the cyclopeptide
      and (2) the presence of a hydrophobic chain or lipidated aminoglucose at the
      appropriate position. Cycloetherification by an intramolecular nucleophilic
      aromatic substitution reaction (S(N)Ar) is used as the key step for the
      construction of the macrocycle. The atropselectivity of this ring-closure
      reaction is found to be sensitive to the peptide backbone and chemoselective
      cyclization (phenol versus primary amine) is achievable. Glycosylation of phenol
      was realized with freshly prepared 3,4,6-tri-O-acetyl-2-N-lauroyl-2-amino-2-deoxy
      alpha-D-glucopyranosyl bromide under phase-transfer conditions. Minimum
      inhibitory concentrations for all of the derivatives are measured by using a
      standard microdilution assay, and potent bioactivities against both sensitive and
      resistant strains are found for some of these compounds (MIC (minimum inhibitory
      concentration) = 4 microg mL(-1) against VRE). From these preliminary SAR
      studies, it was anticipated that both the presence of a hydrophobic substituent
      and an appropriate structure of the macrocycle were required for this series of
      compounds to be active against VRE.

PMID- 16634108
TI  - Facilitated hydrogen storage in NaAlH4 supported on carbon nanofibers.

PMID- 16634109
TI  - A biocatalytic Henry reaction--the hydroxynitrile lyase from Hevea brasiliensis
      also catalyzes nitroaldol reactions.

PMID- 16634110
TI  - Attenuation of a vaccine strain of vaccinia virus via inactivation of interferon
      viroceptor.
AB  - BACKGROUND: Interferons (IFNs) play an important role in host antiviral
      responses, but viruses, including vaccinia viruses (VV), employ mechanisms to
      disrupt IFN activities, and these viral mechanisms are often associated with
      their virulence. Here, we explore an attenuation strategy with a vaccine strain
      of VV lacking a virus-encoded IFN-gamma receptor homolog (viroceptor). METHODS:
      To facilitate the monitoring of virus properties, first we constructed a Lister
      vaccine strain derivative VV-RG expressing optical reporters. Further, we
      constructed a VV-RG derivative, VV-RG8, which lacks the IFN-gammaR viroceptor
      (B8R gene product). Replication, immunological and pathogenic properties of the
      constructed strains were compared. RESULTS: Viruses did not show significant
      differences in humoral and cellular immune responses of immune-competent mice.
      Replication of constructed viruses was efficient both in vitro and in vivo, but
      showed marked difference in kinetics of propagation. In cultured CV-1 epithelial
      cells, the VV-RG8 strain retained the propagation potential of the parental
      virus, while, in the C6 glial cells, significant delay was observed in the
      kinetics of the VV-RG8 replication cycle compared to VV-RG. The pathogenesis of
      the viruses was tested by survival assay and biodistribution in nude mice. High
      dose inoculation of nude mice with VV-RG8 caused less pronounced virus
      dissemination, improved weight gain, and increased survival rate, as compared
      with the VV-RG strain. CONCLUSIONS: The replication-competent virus VV-RG8
      carrying a mutation at the B8R gene is less pathogenic for mice than the parental
      vaccine virus. We anticipate that step-wise inactivation of VV vaccine genes
      involved in evasion of host immune response may provide an alternative approach
      for generation of hyper-attenuated replication-competent vaccines.

PMID- 16634111
TI  - Maternal age-specific fetal loss rates in Down syndrome pregnancies.
AB  - OBJECTIVES: Pregnancies affected by Down syndrome (DS) have a greater risk of
      spontaneous fetal loss than those that are unaffected. In this article, we
      investigate the relationship between maternal age and the risk of spontaneous
      fetal loss in DS pregnancies. METHODS: Fetal loss at different maternal ages were
      estimated by survival analysis using follow-up of 5177 prenatally diagnosed
      cases. The maternal age effect on loss rate was subsequently confirmed by a re
      analysis of published comparisons of the maternal age-specific prevalence of DS
      at different gestational ages. RESULTS: The average fetal loss rate between the
      time of chorionic villus sampling (CVS) and term was 32% (95% CI: 26-38),
      increasing from 23% (95% CI: 16-31) for women aged 25 to 44% (33-56) for women
      aged 45. The average fetal loss rate between the time of amniocentesis and term
      was 25% (21-31), increasing from 19% (14-27) to 33% (26-45) across the same age
      range. CONCLUSION: The fetal loss rate in DS pregnancies increases with maternal
      age, and this has consequences when estimating the live birth prevalence of DS in
      the presence of prenatal diagnosis and termination, and when assessing the
      performance of prenatal screening techniques.

PMID- 16634112
TI  - Gender differences in caregiving stress among caregivers of cancer survivors.
AB  - Despite a growing body of research on male caregivers, limited information is
      available on male caregivers of cancer survivors. Furthermore, few studies have
      examined the unique contribution of caregiver esteem as well as care-recipient's
      functional status as potential mediators of the link between gender and
      caregiving stress. Thus, the present study examines how the caregiver's
      perception of providing care to a spouse with cancer differs by gender. The
      proposed mediators, caregiver's esteem and care-recipient's psychosocial and
      physical functioning, were tested simultaneously, utilizing structural equation
      modeling. Results revealed that both caregiver's esteem and care-recipient's
      psychosocial functioning were significant mediators, but in different directions.
      Specifically, husband caregivers reported higher caregiver's esteem, which
      resulted in reporting less stress from providing care to their wife with cancer.
      On the other hand, when husband caregivers provided care to their wife with
      poorer psychosocial functioning, they reported greater stress from caregiving.
      Husband caregivers will benefit from programs designed to educate them to
      effectively assist their wife's psychosocial adjustment to cancer by reducing
      their stress from providing care.

PMID- 16634113
TI  - Immobilization of gene vectors on polyurethane surfaces using a monoclonal
      antibody for localized gene delivery.
AB  - BACKGROUND: Conventional strategies of gene therapy using viral vectors result in
      suboptimal localization and potentially dangerous distal spread of vector. We
      hypothesized that localized delivery of adenoviral gene vectors could be achieved
      from a polyurethane (PU) film through a mechanism involving anti-viral antibody
      tethering. METHODS: PU films were formulated with a collagen coating. Anti
      adenoviral monoclonal antibodies were covalently bound to the collagen surface.
      These antibodies enabled tethering of replication-defective adenoviruses [Ad-GFP
      (encoding green fluorescent protein)] through highly specific antigen-antibody
      affinity. The binding stability and in vitro delivery of virus bound on PU films
      were investigated. Cell culture studies with rat arterial smooth muscle cells
      (A10) assessed transduction on or near the PU matrix. In vivo experiments with
      collagen-coated PU films investigated atrial epicardial implant and subdermal
      implant models in Yorkshire swine. RESULTS: We report for the first time
      successful PU film-based gene delivery using antibody-tethered adenovirus
      encoding the green fluorescent protein (GFP), demonstrating efficient and highly
      localized gene delivery to arterial smooth muscle cells in cell culture and pig
      implant. In comparison, direct injections of viral vectors into subcutaneous
      sites gave sparse, needle-track-oriented GFP expression patterns. CONCLUSION: We
      conclude that PU film is a suitable platform for a localizable viral vector
      delivery system that also prevents systemic spread of vector. Gene delivery using
      PU film-based anti-viral antibody tethering of vectors should be suitable for a
      wide array of single or multiple therapeutic gene strategies, and for further
      device-based gene delivery therapeutic strategies.

PMID- 16634114
TI  - Electronegative low-density lipoprotein subfraction from type 2 diabetic subjects
      is proatherogenic and unrelated to glycemic control.
AB  - BACKGROUND: The physicochemical and biological characteristics of electronegative
      low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2),
      before and after insulin therapy, were studied. METHODS: Total LDL was
      subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange
      chromatography. RESULTS: The proportion of LDL(-) was increased in plasma from
      DM2 patients compared to control subjects (13.8 +/- 4.6% versus 6.1 +/- 2.5, P <
      0.05) and was not modified after glycemic optimization (14.0 +/- 5.9%). LDL(-)
      from DM2 patients presented similar differential characteristics versus LDL(+)
      than LDL(-) from controls; that is, decreased apoB and oxidizability, and
      increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III,
      platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No
      difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or
      glycated low-density lipoprotein (gLDL) was observed between LDL subfractions.
      Concerning differences between LDL subfractions isolated from DM2 and from
      control subjects, the former showed increased MDA, fructosamine and gLDL
      proportion and decreased LDL size and antioxidant content. The only effect of
      glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2
      subjects. LDL(-) from DM2 patients presented low binding affinity to the low
      density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+)
      and two- to threefold increased ability to release interleukin-8 (IL-8) and
      monocyte chemotactic protein 1 (MCP-1) in endothelial cells. CONCLUSION: These
      results suggest that, although nonenzymatic glycosylation and oxidation are
      increased in type 2 diabetes, these features would not be directly involved in
      the generation of LDL(-). Moreover, LDL(-) properties suggest that the high
      proportion observed in plasma could promote accelerated atherosclerosis in DM2
      patients through increased residence time in plasma and induction of inflammatory
      responses in artery wall cells.

PMID- 16634115
TI  - Three-year mortality in diabetic patients treated with different combinations of
      insulin secretagogues and metformin.
AB  - BACKGROUND: Several studies have shown an increase of mortality in diabetic
      patients treated with combinations of sulphonylureas and biguanides. Comparisons
      between different insulin secretagogues in combination with metformin with
      respect to all-cause mortality have not been reported so far. METHODS: An
      observational cohort study was performed on a consecutive series of 2002
      outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were
      receiving combinations of insulin secretagogues and biguanides at enrollment.
      Three-year mortality was assessed through research in the City of Florence
      Registry Office. RESULTS: During follow-up, 295 deaths were recorded. Among
      patients on combined secretagogue and biguanide treatment, glibenclamide was
      associated with a significantly higher yearly mortality (8.7%) than repaglinide
      (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p <
      0.0001). After adjusting for potential confounders (including age; duration of
      diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment;
      metformin doses; Charlson co-morbidity score; CCS), mortality remained
      significantly higher in patients treated with combinations of glibenclamide and
      metformin when compared to those treated with different insulin secretagogues (OR
      with 95% CI: 2.09 [1.07;4.11]). CONCLUSIONS: In the present study, sulphonylureas
      with greater selectivity for beta-cell receptors, such as glimepiride and
      gliclazide, were associated with a lower mortality when used in combination with
      metformin in comparison with glibenclamide. Safety of such combinations deserves
      further investigation.

PMID- 16634116
TI  - Exenatide elicits sustained glycaemic control and progressive reduction of body
      weight in patients with type 2 diabetes inadequately controlled by sulphonylureas
      with or without metformin.
AB  - BACKGROUND: In two placebo-controlled 30-week trials, treatment with exenatide
      reduced HbA(1c) and body weight in patients with type 2 diabetes in the context
      of sulphonylurea (SU) or SU plus metformin (MET) as background treatment. This
      analysis examines the effects of 82 weeks of exenatide treatment for participants
      in these earlier 30-week trials. METHODS: Data were pooled from the two pivotal
      trials of exenatide added to SU or SU plus MET. Both 30-week, placebo-controlled
      trials of 5 microg or 10 microg exenatide b.i.d. were followed by 52-week open
      label, uncontrolled extension studies in which all participants received 10
      microg exenatide b.i.d. and continued prior oral therapies. This interim analysis
      includes data for 222 patients who completed 82 weeks of exenatide treatment (61%
      M, age 57 +/- 10 y, weight 99 +/- 21 kg, BMI 34 +/- 6 kg/m(2), HbA(1c)8.4 +/-
      1.0% [mean +/- SD]). RESULTS: Reduction in HbA(1c) from baseline to week 30 (-0.8
      +/- 0.1% and -1.0 +/- 0.1% for 5 microg b.i.d. and 10 microg b.i.d., respectively
      [mean +/- SE]) was sustained up to week 82 (-1.0 +/- 0.1%). Of 207 patients with
      baseline HbA(1c) > 7%, 44% achieved HbA(1c) < or = 7% at week 82. Reduction of
      body weight from baseline to week 30 (-1.4 +/- 0.3 kg and -2.1 +/- 0.3 kg for 5
      microg b.i.d. and 10 microg b.i.d., respectively) was progressive up to week 82 (
      4.0 +/- 0.3 kg). The most frequent adverse events were nausea and hypoglycaemia,
      both generally mild to moderate in intensity. CONCLUSIONS: Exenatide added to
      maximally effective doses of SU or SU plus MET resulted in a sustained reduction
      in HbA(1c) and a progressive reduction in weight over 1 1/2 years.

PMID- 16634117
TI  - Nasal bone length at 11-14 weeks of pregnancy in the Korean population.
AB  - OBJECTIVES: The aim of this study was to provide reference values for nasal bone
      length (NBL) scanned at 11-14 weeks' gestation in the Korean population and
      compare these values with those of the Caucasian and African-American
      populations. METHODS: From April 2004 to July 2004, fetal NBLs were measured in
      well-dated, non-anomalous fetuses at 11-14 weeks' gestation in the Korean
      population. Regression analysis was used to assess the relationship between NBL
      and crown-rump length (CRL), and reference values including the 5th, 50th, and
      95th percentile were calculated for each gestational age. The reference values in
      our study were compared with those of the Caucasian and African-American
      populations. RESULTS: A total of 982 cases were prospectively included in the
      study. NBL increased linearly with advance in CRL and was described by the
      equation; NBL (mm) = 0.433 + 0.022 x CRL (mm), R(2) = 0.37. The median values
      (5%, 95%) were 1.5 mm (1.2 mm, 1.9 mm), 1.7 mm (1.4 mm, 2.1 mm), 1.9 mm (1.6 mm,
      2.3 mm), and 2.1 mm (1.7 mm, 2.6 mm) for 11, 12, 13, and 14 weeks' gestation,
      respectively. The median values for each gestational age in the Korean population
      were significantly lower than those in the Caucasian and African-American
      populations (P < 0.0001). CONCLUSION: There is a difference in NBL scanned at 11
      14 weeks' gestation between the Korean and the Caucasian/African-American
      populations, and so racial adjustment is needed in the evaluation of the fetal
      nasal bone for current first-trimester screening.

PMID- 16634118
TI  - Three-stage contingent screening for Down syndrome.
AB  - OBJECTIVE: To demonstrate the potential value of three-stage sequential screening
      for Down syndrome. METHODS: Protocols were considered in which maternal serum
      pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic
      gonadotropin (hCG) measurements were taken on all women in the first trimester.
      Those women with very low Down syndrome risks were screened negative at that
      stage and nuchal translucency (NT) was measured on the remainder and the risk
      reassessed. Those with very low risk were then screened negative and those with
      very high risk were offered early diagnostic testing. Those with intermediate
      risks received second-trimester maternal serum alpha-fetoprotein, free beta-hCG,
      unconjugated estriol and inhibin-A. Risk was then reassessed and those with high
      risk were offered diagnosis. Detection rates and false-positive rates were
      estimated by multivariate Gaussian modelling using Monte-Carlo simulation.
      RESULTS: The modelling suggests that, with full adherence to a three-stage
      policy, overall detection rates of nearly 90% and false-positive rates below 2.0%
      can be achieved. Approximately two-thirds of pregnancies are screened on the
      basis of first-trimester biochemistry alone, five out of six women complete their
      screening in the first trimester, and the first-trimester detection rate is over
      60%. CONCLUSION: Three-stage contingent sequential screening is potentially
      highly effective for Down syndrome screening. The acceptability of this protocol
      and its performance in practice, should be tested in prospective studies.

PMID- 16634119
TI  - The incidence of pancytopenia in patients taking leflunomide alone or with
      methotrexate.
AB  - PURPOSE: To estimate the incidence of pancytopenia in patients taking leflunomide
      with or without methotrexate in Australia. METHODS: Review of spontaneous reports
      to the Australian Adverse Drug Reactions Advisory Committee (ADRAC); estimation
      of incidence using national prescription reimbursement data; concomitant exposure
      to methotrexate was estimated using three sources of information. RESULTS: ADRAC
      received 11 reports of pancytopenia (meeting predefined criteria) associated with
      the use of leflunomide during its first 31 months of marketing. In nine reports,
      the patients were also taking methotrexate. Estimates of incidence in patients
      taking leflunomide alone ranged from 1 in 3698 to 1 in 4582 patients exposed; for
      patients also taking methotrexate the estimates ranged from 1 in 575 to 1 in 822.
      CONCLUSIONS: Use of methotrexate with leflunomide increases the risk of
      pancytopenia compared with use of leflunomide alone. The haematological toxicity
      of the combination requires further study.

PMID- 16634120
TI  - Measurement of changes in antihypertensive drug utilisation following primary
      care educational interventions.
AB  - PURPOSE: To measure changes in drug utilisation following a national general
      practice education program aimed at improving prescribing for hypertension.
      METHODS: A series of nationally implemented, multifaceted educational
      interventions using social marketing principles focusing on prescribing for
      hypertension, was commenced in October 1999, and repeated in September 2001 and
      August 2003. The target group was all primary care prescribers in Australia and
      interventions were both active (voluntary) and passive. Newsletter and
      prescribing feedback was mailed in October 1999, September 2001 (newsletter only)
      and August 2003. Approximately a third of general practitioners (GPs) in
      Australia undertook at least one active educational activity (clinical audit,
      educational visit or case study) during the period October 1999-April 2004.
      National dispensing data from 1996 to 2004 were analysed using time series
      methodology with a decay term for intervention effect, to assess trends in
      prescribing of various classes of antihypertensives. In particular, the program
      aimed to increase the prescribing of thiazide diuretics and beta blockers.
      RESULTS: Consistent with key intervention messages, the program achieved an
      increase in low-dose thiazide and beta blocker prescribing. The rate of
      prescribing of low-dose thiazides doubled from 1.1 per 1000 consultations in
      October 1999 to 2.4 per 1000 in October 2003. Beta-blocker utilisation showed a
      more modest but significant increase over the time of the study, with the change
      in observed versus expected rate of prescribing increasing by 8% by April 2004.
      Therapeutic options for treating hypertension changed markedly in the time of the
      study with the advent of ACE inhibitor/Angiotensin II receptor antagonists and
      thiazide combination products. It is important, therefore, to interpret the
      results in light of these changes. CONCLUSION: A national education program aimed
      at GPs was successful in improving prescribing for hypertension. Lessons learned
      will be applied in evaluation of future NPS programs and are also applicable to
      analysis of other interventions aimed at influencing prescribing behaviour.

PMID- 16634121
TI  - Outpatient drug safety: new steps in an old direction.
AB  - Iatrogenic injury from adverse drug events (ADEs) is a common and often
      preventable problem in modern medical practice. Attention to this problem has
      focused on the inpatient hospital setting and healthcare professionals. However,
      most medication is prescribed and used outside of hospitals and is managed by
      patients or lay caregivers in homes or workplaces. To address the public health
      problem of outpatient drug safety, interventions to prevent adverse events must
      recognize the central role of the patient in medication management and
      environmental factors specific to the outpatient setting. Lessons and techniques
      from the field of injury prevention should guide the development and
      implementation of safety interventions. First, Haddon's phase-factor matrix can
      be used to help conceptualize outpatient drug safety interventions. Second,
      interventions to improve outpatient drug safety should be patient-centered and
      extend beyond patient education to include engineering innovations and
      enforcement strategies. Third, the sustainability of active versus passive
      interventions should be considered when choosing safety interventions.

PMID- 16634122
TI  - Euchromatic variant 16p+. Implications in prenatal diagnosis.
AB  - BACKGROUND: Euchromatic imbalances at the cytogenetic level are usually
      associated with phenotypic consequences. Among the exceptions are euchromatic
      variants of chromosome 16 (16p+) with normal phenotype. There is a growing list
      of euchromatic duplications and deletions involving both G-positive and G
      negative bands that seem to be phenotypically neutral, but these euchromatic
      variants are rare. OBJECTIVE: The aim of this report is to describe a new
      familial case of euchromatic variant 16p+ and to emphasise the misinterpretation
      of these rare euchromatic variants particularly when ascertained at prenatal
      diagnosis. METHODS AND RESULTS: Fluorescence in situ hybridisation with clone
      RP11-261A7 showed an amplified signal in the larger chromosome 16. This clone
      contains FLJ43855 gene, similar to sodium- and chloride-dependent creatine
      transporter. CONCLUSION: So, this 16p+ variant that involves amplification of
      pseudogenetic sequences is considered a polymorphism in normal individuals.

PMID- 16634123
TI  - Effect on Down syndrome screening performance of adjusting for marker levels in a
      previous pregnancy.
AB  - OBJECTIVES: In prenatal screening for Down syndrome, serum marker values can be
      adjusted using values from a previous pregnancy to avoid the problem of women
      having a high chance of recurrent false-positive results. We investigate the
      effect of such adjustment on overall screening performance. METHODS: Monte Carlo
      simulation was used to investigate the effect of this adjustment on five widely
      used screening tests for Down syndrome (Triple, Quadruple, Combined, serum
      Integrated, Integrated tests). RESULTS: Adjustment for screening marker values
      (expressed in multiples of the median, (MoM)) in a previous pregnancy improved
      screening performance. The detection rate for a 1% false-positive rate (FPR)
      increased from 54 to 59% with the Triple test, from 63 to 68% with the Quadruple
      test, from 70 [corrected] to 75% for the Combined test, from 70 [corrected] to
      76% for the serum Integrated test, and from 85 to 88% for the Integrated test.
      The FPR for an 85% detection rate decreased from 10 to 7.9%, 7.1 to 4.9%, 4.9 to
      3.7%, 4.7 to 2.9% and 1.1 to 0.7% respectively for the five tests. Among women
      who have had a false-positive result in a previous pregnancy, adjustment
      substantially lowers the false-positive rate, for example, from 18 [corrected] to
      7.3% with the Combined test using a 1 in 250 risk cut-off. CONCLUSION: MoM
      adjustment for values in a previous pregnancy improves overall screening
      performance and substantially reduces the high recurrent false-positive rate.
      This adjustment can be routinely applied in screening programmes through the
      screening software used to interpret a woman's screening results.

PMID- 16634124
TI  - Enrichment of NRBC in maternal blood: a more feasible method for noninvasive
      prenatal diagnosis.
AB  - OBJECTIVE: To assess the efficiency and reliability of the separation of fetal
      nucleated red blood cells (NRBCs) using the galactose-specific lectin method, we
      counted the number of NRBCs in the blood of pregnant women at various gestational
      ages, as well as after amniocentesis and termination. METHOD: Peripheral blood
      samples were obtained from (1) 22 singleton pregnant women (between 9 and 34
      weeks of gestation) and from 23 women who underwent termination (between 6 and 19
      weeks of gestation). To determine whether amniocentesis influences numbers of
      NRBCs, five samples were obtained (2) before and after the procedure. NRBC
      enrichment was initially performed using density gradients and subsequently using
      galactose-specific lectin. The cells were then stained with May-Gruenwald Giemsa
      (MGG) and counted under a light microscope. RESULTS: NRBCs were found in all
      samples, ranging from 1 to 82 (median = 12.5 cells/sample). The multiples of the
      median (MoM) conversion of the number of cells revealed a raise of 1.66-fold
      (0.12-6.64) in post-termination samples compared with the control value of 1.00
      MoM (0.11-6.92; p = 0.036). The postamniocentesis increase was, instead, 1.11
      fold (0.17-4.02), which did not reach statistical significance. CONCLUSION: All
      blood samples tested contained NRBCs. Samples obtained after termination yielded
      more cells than those obtained from women whose pregnancies were going on
      normally. The number of NRBCs in post-termination samples after MoM conversion
      differed significantly from those in controls. Although separation of NRBCs was
      not feasible due to extremely low numbers, our results indicated that NRBCs are
      detectable in all blood samples from normal pregnant women.

PMID- 16634125
TI  - Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2
      diabetes mellitus.
AB  - BACKGROUND: Oxidative stress plays an important role in the pathophysiology of
      diabetes mellitus. The aim of this study was to evaluate the formation of
      cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with
      impaired glucose tolerance (IGT) and diabetes. METHODS: Blood plasma levels of
      cholesterol oxidation products were determined in the following groups: type 1
      diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT),
      children without diabetes (C1) and adults without diabetes (C2). The serum levels
      of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH),
      cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta
      hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta
      triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol
      5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol
      5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25
      OH) (trivial name and abbreviations indicated in parentheses) were quantified by
      gas chromatography using flame ionization detection. RESULTS: The levels of total
      ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects
      without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol,
      cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood
      plasma of subjects in the DM2 group than in the blood plasma of subjects in the
      C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral
      hypoglycemic drugs associated with insulin resulted in lower concentrations of
      nitrotyrosine in the blood plasma without significant changes in the
      concentrations of glucose and glycated hemoglobin. Moreover, combination with
      statins in both treatments decreased the concentrations of ChOx. CONCLUSIONS:
      ChOx are suitable biomarkers of oxidative stress and may be useful in clinical
      studies to follow drug effects on lipid oxidative modifications in diabetic
      patients.

PMID- 16634126
TI  - The impact of diagnosis and plaque radiotherapy treatment of malignant choroidal
      melanoma on patients' quality of life.
AB  - Quality of life (QOL) has become an important outcome criterion of medical
      interventions, but the impact of diagnosis and radiotherapy on QOL in patients
      with malignant choroidal melanoma (MCM) has rarely been studied. Inventories
      covering global (SF-36) and disease-specific QOL (NEI-VFQ), mental distress (SCL
      90-R), and social support (K-22, German) were applied to a consecutive sample of
      MCM-patients scheduled for plaque radiotherapy. Data were gathered preoperatively
      (t(0)) and 3 months postoperatively (t(1), except for the K-22, which was applied
      at t(0) only). Fifty-four patients took part in both surveys, the number of
      patients with visual impairment increased from 21 preoperatively to 34
      postoperatively. Global QOL of MCM-patients was significantly reduced compared to
      the healthy norm and other ophthalmological patients both at t(0) and t(1).
      Clinically relevant distress was present in every second patient at t(0) and
      every third patient at t(1), social support was not impaired. Global and disease
      specific QOL declined significantly from t(1) to t(0). The MCM diagnosis
      compromises QOL, which is additionally impaired by radiotherapy. Regular QOL
      assessment can help to identify patients at risk, facilitate provision of
      psychosocial treatment and may thus improve patient satisfaction.

PMID- 16634127
TI  - Synthesis, chiral HPLC resolution and configuration assignment of 1
      phenylglyceryl trinitrate stereomers.
AB  - As an introductory study of in vitro vasodilating activity, the access to the
      four stereomers of 1-phenylglyceryl trinitrate is described using achiral and
      chiral chromatography. For semi-preparative separation of the enantiomers, a
      Chiralcel OD (250 x 10 mm, 10 microm) was used. Catalytic reduction leading to
      the corresponding stereomers of 1-phenylglycerol allowed absolute configuration
      assignments. The same methods were used for the separation and configuration
      assignment of the enantiomers of 3-phenylpropane-1,2-diyl dinitrate.

PMID- 16634128
TI  - Synthesis of new enantiomerically pure macrocycles containing phenanthroline
      subunits.
AB  - New enantiomerically pure macrocycles have been prepared by combining 1,10
      phenanthroline 2,9-dicarboxylic acid and two alpha-amino-acids linked through
      spacers. Different diamine linkers have been employed in order to modify the
      dimensions and the properties of the macrocycles whose structures have been
      studied by 1H and 13C NMR spectroscopy. The ability of the (L)-valine containing
      macrocycles to bind metal ions and phenolic molecules has been investigated by 1H
      NMR experiments and Molecular Mechanics calculations.

PMID- 16634129
TI  - Dynamic ligand-exchange chiral stationary phase from S-benzyl-(R)-cysteine.
AB  - S-benzyl-(R)-cysteine (R-SBC) is a new chiral ligand-exchange stationary phase
      which has proved to be effective in the analytical separation of some natural and
      unnatural underivatized amino acids with fair to good separation and resolution
      factors. The dynamic coating of the RP-18 solid support with S-Benzyl-(R)
      cysteine (R-SBC) gives rise to a stable and efficient chiral stationary phase
      (CSP) that has been successfully employed. The mechanism of chiral recognition is
      discussed and a molecular modeling study aimed at identifying molecular
      descriptors responsible for observed different behaviours of analytes upon
      different albeit closely related selectors is discussed.

PMID- 16634130
TI  - Chirality as an inherent general property of matter.
AB  - A statement has been formulated that chirality is an indispensable inherent
      property of all material objects, at one level of organization of matter or
      another. The translation of chirality from one level of material objects to
      another deserves our attention. The parity violation of weak interactions can be
      discussed in terms of the homochirality of the pool of fundamental particles, as
      it translates into optical activity of metal vapors. Individual photons and
      energy quanta are considered to be chiral entities, too, since they can be
      separated into beams of circularly polarized radiation. The chiral structure of
      the universe has been proposed and a method of determining the orientation of the
      axis of rotation of the universe suggested.

PMID- 16634131
TI  - Enantiomeric separation of mineralocorticoid receptor (hMR) antagonists using the
      Chiralcel OJ-H HPLC column with novel polar cosolvent eluent systems.
AB  - This study demonstrates the increased versatility of the Chiralcel OJ-H
      stationary phase when using various alcohol/acetonitrile mobile phases. This
      chiral stationary phase has traditionally been employed in the normal phase mode
      and more recently with neat alcohols as eluents. Selected isomeric human
      mineralocorticoid receptor (hMR) antagonist pharmaceutical candidates and
      synthetic intermediates were separated using the Chiralcel OJ-H HPLC column with
      novel polar cosolvent eluent systems. The capacity factors, resolution, and
      selectivity of the chiral separations were assessed while varying the
      alcohol/acetonitrile composition and alcohol identity. The mixed polar eluents
      provide separations that are nearly always superior to both the traditional
      hexane-rich and single-alcohol "polar organic" eluents for the compounds tested
      in this article.

PMID- 16634132
TI  - Enantiophore modeling in 3D-QSAR. A data mining application on Whelk-O1 chiral
      stationary phase.
AB  - A combination of the enantiophore concept described in a previous study and a
      quantitative structure enantioselective relationship (QSER) based on partial
      least squares (PLS) analysis is presented. In the present study, a comprehensive
      approach for describing the enantioselective binding properties of the Whelk-O1
      chiral HPLC receptor is achieved using molecular descriptors calculated by the
      GRID program. The GRID descriptors allow us to describe the molecules in terms of
      their ability to form favorable interactions with independent chemical groups
      (probes) that can be related to receptor sites. For each molecule, we compute 120
      enantiophore descriptors representing the energy contributions from all possible
      pairwise combinations of probes. The overall procedure was simplified by
      considering only the most energetically favorable locations and converting
      selected grid-point energies into alignment-independent descriptors. By using a
      training set of 143 diverse chiral compounds, an optimal PLS model requiring
      seven components was chosen by using the cross-validation method resulting in a
      correlation coefficient R2= 0.88 and a cross validated correlation coefficient
      Q2= 0.85. An interpretation of the model is proposed based upon a visual
      inspection of the regression coefficient plots. From these plots, the influence
      of particular molecular features for selective binding of solutes was estimated
      and used to outline the chiral recognition sites in the Whelk-O1 receptor. The
      predictive power of our model has been estimated by means of an external data set
      emphasizing the suitability of the procedure also for predictive aims.

PMID- 16634133
TI  - Vancomycin as chiral selector for enantioselective separation of selected profen
      nonsteroidal anti-inflammatory drugs in capillary liquid chromatography.
AB  - The chiral selector vancomycin was used either as mobile phase additive or bound
      as a chiral stationary phase (CSP) for the stereoselective separation of seven
      racemic nonsteroidal anti-inflammatory drugs (NSAIDs), fenoprofen, carprofen,
      flurbiprofen, indoprofen, flobufen, ketoprofen, and suprofen, by capillary liquid
      chromatography. The effect of the type of stationary phase, the chiral column
      Chirobiotic V or the achiral stationary phases Nucleosil 100 C8 HD and Nucleosil
      100 C18 HD, and the concentration of vancomycin in the mobile phase on separation
      of the drug enantiomers were evaluated. All the drugs, except flobufen, were
      successfully enantioseparated on Nucleosil 100 C8 HD with 4 mM vancomycin present
      in the mobile phase (composed of methanol and buffer) in the reversed phase mode.
      On the vancomycin-bonded chiral stationary phase, it was difficult to get
      enantioseparations of the profen NSAIDs. However, flobufen gave better
      enantioseparation on the vancomycin CSP. The better enantioresolution of the
      majority of profen derivatives on the achiral columns with vancomycin added to
      the mobile phase can be attributed in particular to the higher separation
      efficiency of this capillary chromatographic system. In addition, vancomycin
      dimers, formed in the mobile phase, seem to offer a better steric arrangement for
      stereoselective interaction to these analytes than the vancomycin bonded on the
      CSP. These substantial differences in the CS structure significantly influence
      the chiral discrimination mechanism.

PMID- 16634134
TI  - Chest X-ray quiz. Subcutaneous emphysema on the left lateral wall.

PMID- 16634135
TI  - The immune system in the fight against cancer.

PMID- 16634136
TI  - [Frontotemporal dementia].

PMID- 16634138
TI  - Nuclear cardiology in the literature.

PMID- 16634137
TI  - The promise of I-123 radiotracers.

PMID- 16634139
TI  - Assessing clinical trial results.

PMID- 16634141
TI  - Bibliography. Current world literature. Respiratory infections.

PMID- 16634140
TI  - Assessing clinical trial results.

PMID- 16634142
TI  - Bibliography of food microbiology.

PMID- 16634143
TI  - PA: RN supervisor 'props' door to nsg. home: termination & disqualification for
      UI result.

PMID- 16634144
TI  - The diverse roles of J-proteins, the obligate Hsp70 co-chaperone.
AB  - Hsp70s and J-proteins, which constitute one of the most ubiquitous types of
      molecular chaperone machineries, function in a wide variety of cellular
      processes. J-proteins play a central role by stimulating an Hsp70's ATPase
      activity, thereby stabilizing its interaction with client proteins. However,
      while all J-proteins serve this core purpose, individual proteins are both
      structurally and functionally diverse. Some, but not all, J-proteins interact
      with client polypeptides themselves, facilitating their binding to an Hsp70. Some
      J-proteins have many client proteins, others only one. Certain J-proteins, while
      not others, are tethered to particular locations within a cellular compartment,
      thus "recruiting" Hsp70s to the vicinity of their clients. Here we review recent
      work on the diverse family of J-proteins, outlining emerging themes concerning
      their function.

PMID- 16634145
TI  - Role of the mediator complex in nuclear hormone receptor signaling.
AB  - Mediator is an evolutionarily conserved multisubunit protein complex that plays a
      key role in regulating transcription by RNA polymerase II. The complex functions
      by serving as a molecular bridge between DNA-bound transcriptional activators and
      the basal transcription apparatus. In humans, Mediator was first characterized as
      a thyroid hormone receptor (TR)-associated protein (TRAP) complex that
      facilitates ligand-dependent transcriptional activation by TR. More recently,
      Mediator has been established as an essential coactivator for a broad range of
      nuclear hormone receptors (NRs) as well as several other types of gene-specific
      transcriptional activators. A single subunit of the complex, MED1/TRAP220, is
      required for direct ligand-dependent interactions with NRs. Mediator coactivates
      NR-regulated gene expression by facilitating the recruitment and activation of
      the RNA polymerase II-associated basal transcription apparatus. Importantly,
      Mediator acts in concert with other NR coactivators involved in chromatin
      remodeling to initiate transcription of NR target genes in a multistep manner. In
      this review, we summarize the functional role of Mediator in NR signaling
      pathways with an emphasis on the underlying molecular mechanisms by which the
      complex interacts with NRs and subsequently facilitates their action. We also
      focus on recent advances in our understanding of TRAP/Mediator's
      pathophysiological role in mammalian disease and development.

PMID- 16634146
TI  - An update on acid secretion.
AB  - Gastric acid secretion is a complex process that requires hormonal, neuronal, or
      calcium-sensing receptor activation for insertion of pumps into the apical
      surface of the parietal cell. Activation of any or all these pathways causes the
      parietal cell to secrete concentrated acid with a pH at or close to 1. This
      acidic fluid combines with enzymes that are secreted from neighbouring chief
      cells and passes out of the gland up through a mucous gel layer covering the
      surface of the stomach producing a final intragastric pH of less than 4 during
      the active phase of acid secretion. Defects in either the mucosal barrier or in
      the regulatory mechanisms that modulate the secretory pathways will result in
      erosion of the barrier and ulcerations of the stomach or esophagus. The entire
      process of acid secretion relies on activation of the catalytic cycle of the
      gastric H+,K+-ATPase, resulting in the secretion of acid into the parietal cell
      canaliculus, with K+ being the important and rate-limiting ion in this activation
      process. In addition to K+ as a rate limiter for acid production, Cl- secretion
      via an apical channel must also occur. In this review we present a discussion of
      the mechanics of acid secretion and a discussion of recently identified
      transporter proteins and receptors. Included is a discussion of some of the
      recent candidates for the apical K' recycling channel, as well as two recently
      identified apical proteins (NHE-3, PAT-1), and the newly characterized calcium
      sensing receptor (CaSR). We hope that this review will give additional insight
      into the complex process of acid secretion.

PMID- 16634147
TI  - Structure-function relationship of the TRP channel superfamily.
AB  - Transient receptor potential (TRP) channels are involved in the perception of a
      wide range of physical and chemical stimuli, including temperature and osmolarity
      changes, light, pain, touch, taste and pheromones, and in the initiation of
      cellular responses thereupon. Since the last decade, rapid progress has been made
      in the identification and characterization of new members of the TRP superfamily.
      They constitute a large superfamily of cation channels that are expressed in
      almost all cell types in both invertebrates and vertebrates. This review
      summarizes and discusses the current knowledge on the TRP protein structure and
      its impact on the regulation of the channel function.

PMID- 16634148
TI  - The vertebrate phototransduction cascade: amplification and termination
      mechanisms.
AB  - The biochemical cascade which transduces light into a neuronal signal in retinal
      photoreceptors is a heterotrimeric GTP-binding protein (G protein) signaling
      pathway called phototransduction. Works from psychophysicists,
      electrophysiologists, biochemists, and geneticists over several decades have come
      together to shape our understanding of how photon absorption leads to
      photoreceptor membrane hyperpolarization. The insights of phototransduction
      provide the foundation for a mechanistic account of signaling from many other G
      protein-coupled receptors (GPCR) found throughout nature. The application of
      reverse genetic techniques has strengthened many historic findings and helped to
      describe this pathway at greater molecular details. However, many important
      questions remain to be answered.

PMID- 16634149
TI  - Back care: overcoming pain and staying active. Exercise, posture, surgical
      options, new therapies and more.

PMID- 16634150
TI  - A life saved: heart attack care at its best. What you can learn from a medical
      team's response to a close call.

PMID- 16634151
TI  - A treatment for snoring may help fight heart disease.

PMID- 16634152
TI  - How to use beta-blockers safely. Managing these powerful medications calls for
      extra care.

PMID- 16634153
TI  - Guard against clots in leg veins. Stretch, walk, learn symptoms to prevent
      serious blockages.

PMID- 16634154
TI  - Hormone replacement for men? Why you should be cautious about a new testosterone
      study.

PMID- 16634155
TI  - I hear a lot about how exercise is good for the heart, but I've never heard
      anything about why it works. How does exercise help? And do I have to work out
      every day?

PMID- 16634156
TI  - [Reduction of harm. Strategies for longer and better life].

PMID- 16634157
TI  - [Services for drug users. Making a difference in many lives].

PMID- 16634158
TI  - [ESAP. More access to syringes].

PMID- 16634159
TI  - [Hepatitis C and the users of intravenous drugs].

PMID- 16634161
TI  - [The 110th annual meeting of the Japanese Ophthalmological Society. Osaka, Japan.
      April 13-16, 2006. Abstracts].

PMID- 16634160
TI  - New route of importation of Mycobacterium tuberculosis Beijing genotype.

PMID- 16634162
TI  - [The 107th annual meeting of the Japan Surgical Society. Tokyo, Japan.  March 29
      31, 2006. Abstracts].

PMID- 16634163
TI  - [The 81st annual meeting of the Japanese Society for Tuberculosis. Sendai, Japan.
      April 26-28, 2006. Program and Abstracts].

PMID- 16634164
TI  - [The 94th annual meeting of the Japanese Urological Association. Fukuoka, Japan.
      April 12-15, 2006. Abstracts].

PMID- 16634165
TI  - [The 102nd annual meeting of the Japanese Society of Psychiatry and Neurology.
      Fukuoka, Japan. May 11-13, 2006. Program].

PMID- 16634166
TI  - Medicare program; requirements for providers and suppliers to establish and
      maintain Medicare enrollment. Final rule.
AB  - This final rule requires that all providers and suppliers (other than physicians
      or practitioners who have elected to "opt-out" of the Medicare program) complete
      an enrollment form and submit specific information to us. This final rule also
      requires that all providers and suppliers periodically update and certify the
      accuracy of their enrollment information to receive and maintain billing
      privileges in the Medicare program. In addition, this final rule implements
      provisions in the statute that require us to ensure that all Medicare providers
      and suppliers are qualified to provide the appropriate health care services.
      These statutory provisions include requirements meant to protect beneficiaries
      and the Medicare Trust Funds by preventing unqualified, fraudulent, or excluded
      providers and suppliers from providing items or services to Medicare
      beneficiaries or billing the Medicare program or its beneficiaries.

PMID- 16634167
TI  - Evaluating the oversight of scientific misconduct.
AB  - The Office of Research Integrity has proposed a new definition of scientific
      misconduct that will substantively reduce the federal government's role of
      oversight of scientific practices. The standard is being changed despite the lack
      of evidence about the effects of current policies or understanding of why
      research misconduct occurs, how it can be detected and prevented, and the nature
      and effectiveness of sanctions. Given this lack of knowledge and the perception
      that the integrity of science is falling, we believe it would be unwise for the
      academic and scientific community to adopt this new standard.

PMID- 16634168
TI  - Researchers' views of the acceptability of restrictive provisions in clinical
      trial agreements with industry sponsors.
AB  - We conducted a mail survey of 884 U.S. medical school faculty active in clinical
      research to elicit their views about the acceptability of provisions in contracts
      for industry-sponsored clinical trials that would restrict investigators'
      academic freedom and control over trials. We compared their responses to results
      from a similar survey of research administrators at 107 medical schools. There
      was substantial variation among clinical researchers in their acceptability
      judgments, with a relatively large proportion of clinical trial investigators
      willing to accept provisions that give industry sponsors considerable control
      over the dissemination of research results. There were significant differences in
      the perceptions of clinical trial investigators versus other recently published
      clinical researchers; investigators with a high versus low percentage of research
      support from industry; junior versus senior faculty; and investigators at
      institutions with high versus low National Institute of Health (NIH) funding
      ranks. There was also a significant divergence of views in a number of areas
      between clinical trialists and research administrators who negotiate clinical
      trial contracts on their behalf. Medical school faculty could benefit from
      additional guidance about what their institution views as acceptable parameters
      for industry-sponsored clinical trial agreements.

PMID- 16634169
TI  - [Pregnant woman with hyperemesis, confusion, ataxia and nystagmus].

PMID- 16634170
TI  - [Pregnancy, nausea and vomiting].

PMID- 16634171
TI  - Awareness of publication guidelines and the responsible conduct of research.
AB  - We have conducted a longitudinal survey of NIH-funded F32 postdoctoral fellows to
      determine if mandated instruction in the responsible conduct of research (RCR)
      has measurable effects on awareness of, attentiveness to, and behavioral
      judgments about research ethics and authorship and publication. Of 418 F32
      fellows participating in the study, 50% were aware of and had referred to
      guidelines on authorship and publication practices while 50% were either unaware
      of or had not referred to guidelines. Groups were similar with regard to total
      number of peer-reviewed publications and total number of first author
      publications, years of research experience, years since completing their doctoral
      degree, and receipt of RCR training. The equal distribution of guideline
      awareness and use, and group similarities with regard to career development and
      achievement provided us with an opportunity to consider whether awareness of and
      use of guidelines is associated with broader judgments about author roles and
      responsibilities. The findings suggest that awareness and utilization of
      guidelines are, at best, only modestly associated with more ethically appropriate
      judgments and attitudes about author roles and responsibilities among novice
      F32's.

PMID- 16634172
TI  - Assessing the educational literature in the responsible conduct of research for
      core content.
AB  - To determine core content for RCR instruction, content analysis was conducted
      using key instructional resources for ORI's nine RCR "core instructional areas".
      Topics discussed in these key RCR resources were identified and their frequency
      across resources was tabulated. Topics covered most frequently were judged to be
      core content. Although key educational resources cited a variety of references,
      specific topics and issues addressed were generally consistent across the
      materials examined. Nonetheless, key resources varied in organization and depth
      of coverage for core instructional areas. Recent resources were more systematic
      and comprehensive than earlier works. This was particularly evident in materials
      about human participant research, conflicts of interest, and data management and
      sharing. Key resources presented additional "non-core" issues, such as scientific
      values, ethical principles, creativity and objectivity, moral reasoning,
      genetics, epidemiological issues, and scientists' societal roles, suggesting that
      ORI's core instructional areas should be reconfigured or expanded. Because
      educational material available on RCR and professionalism was so comprehensive,
      we recommend that ORI consider research integrity, not research misconduct, as
      one core instructional area. We also recommend that compliance with research
      regulations be restored as a core instructional area to accentuate ethical,
      financial and legal requirements related to acceptance of federal funding.

PMID- 16634173
TI  - Research misconduct and crime lessons from criminal science on preventing
      misconduct and promoting integrity.
AB  - For 200 years, criminologists theorized that delinquent and criminal acts arise
      from deviant psychological states (such as irrationality or immorality) and/or
      social conditions that produce these psychological states. This theoretical
      perspective, which is being duplicated in most efforts to understand and control
      research misconduct, has not been productive. More recently, criminological
      perspectives have emerged, emphasizing situational factors that enhance or
      restrict the opportunity for illegal or imprudent behavior. These so-called
      "opportunity" theories have been shown to have practical value in reducing crime
      rates. We explore the promise of these newer theories for the responsible conduct
      of research (RCR).

PMID- 16634174
TI  - Evaluating research misconduct policies at major research universities: a pilot
      study.
AB  - This pilot study evaluates the accessibility and usefulness of the research
      misconduct (RM) policies at the top-25 universities as ranked by NIH and NSF
      grant awards. Measuring accessibility demonstrates how readily-available policies
      are to the people they affect. Evaluating the range of policy content indicates
      whether policies and procedures on research misconduct are "useful" as opposed to
      merely "minimal" (Rhoades, 2003). On average, it took five clicks to get from a
      university's home page to its RM policies. Only nine policies were accessed
      within three or fewer clicks. Policy information was coded into categories
      comprising a total of 20 topic areas, which were then grouped into five content
      domains. The policies reveal a broad range of usefulness. Some provide relevant
      details on almost every topic area, while others leave most questions unanswered.
      Three of the 20 topic areas are almost universally covered in the policies
      analyzed. In contrast, five other topic areas average less than half of the
      information which could have been included. These policies, from elite U.S.
      research universities, may serve as role models; as such they should perhaps be
      held to the highest standards. If the message sent by a policy lacks clarity and
      precision, it should be revised to include an appropriate level of detail.

PMID- 16634175
TI  - The Internet: expanding our capacity for scholarly inquiry in nursing--a reprise.

PMID- 16634176
TI  - Commentary: a reprise.

PMID- 16634177
TI  - Globalization of bioethics as an intercultural social tuning technology.
AB  - Now, in the beginning of the 21st century, bioethics must be urgently globalized
      into a Global Bioethics which combines the ongoing Bioethics based on the modern
      European humanism with the newly arising Environmental Ethics based on the rather
      communitarian (or Asian) ways of thinking. This does not always mean that the new
      global bioethics is necessarily universalistic, for we should stand on the
      recognition of the wide spread variety of value systems in the world, north and
      south, east and west. However, it is not particularistic either, for in order to
      establish a post-modern global ethics, we have to accept and harmonize every kind
      of antagonistic values on the Globe. For this purpose we have to cultivate a new
      social technology of tuning social disorder of not only international but also
      inter-ethnic and inter-cultural level of ideology beyond the modern European
      humanism. Here the concept of "human rights" or the concept of "human dignity"
      may lose its significance as it has held in the past bioethical thinking in the
      western world.

PMID- 16634178
TI  - Japanese discussions on the concept of "person" and its function in bioethics.
AB  - A survey of responses by Japanese bioethicists toward the notion of "person" and
      its use in mainstream Angloamerican bioethics reveals that Japanese bioethics,
      while taking the importance of Angloamerican bioethics as a starting point, has
      quickly moved beyond a mere receptive attitude. This article first briefly
      elucidates the historical background of the Japanese response by sketching out
      earlier accommodations of the philosophical concept of personhood in Japanese
      philosophy. It moves on to explore some of the criticisms levelled at the notion
      of personhood employed by bioethicists like Tooley or Singer, and analyses their
      primary motives and content. The following section introduces A. Muramatsu's
      attempt to critically reconstruct the notion of person, integrating aspects of
      modern philosophy of the human body. The critical evaluation of the theories
      explored makes a strong case for integrating the Japanese bioethical experience
      into the international discussion.

PMID- 16634180
TI  - H5N1 avian influenza, Kampot Province, Cambodia.

PMID- 16634179
TI  - The present state and problems of "The Code of Medical Ethics" in Japan.
AB  - A code of professional ethics for the physician in Japan is being prepared caused
      by the progress of the medical conditions. The Japan Medical Association (JMA)
      enacted "the guideline on professional ethics for the physician" in 2004.
      However, as for the substantial effect of this guideline, it may not be able to
      be expected. The present state of the professional group of the physician in
      Japan can be shown as that reason. (1) First, there is not any physician's group
      of the compulsory admission, but only professional ability profit group of the
      voluntary admission in Japan. (2) There are not ethical regulations of the
      profession which has legal effect to face in the physician's misconduct in Japan.
      (3) In addition, there is not any autonomous organizations inside the
      professional group which examine and impose disciplinary punishment to the
      physician who went through misconduct in Japan. After all, the ethics in the
      physician would be left to each physician's conscience. Then, how should we do to
      solve such various fundamental problems? In this paper, the situation in various
      foreign countries is surveyed as an indication of the Japanese medical
      profession's future conduct. Moreover, I present some solutions to the various
      problems in fulfilling the professional ethics for the physician in Japan.

PMID- 16634181
TI  - Helicobacter pylori and immunocompromised children.

PMID- 16634182
TI  - Community case of methicillin-resistant Staphylococcus aureus infection.

PMID- 16634183
TI  - Rickettsia massiliae human isolation.

PMID- 16634184
TI  - Bertiella studeri infection, China.

PMID- 16634185
TI  - [Child development diagnosis from infancy to preschool age].

PMID- 16634186
TI  - [Abdominal pain in childhood--functional or organically induced?].

PMID- 16634187
TI  - [Changes in the composition of infant formula].

PMID- 16634188
TI  - [Better iodine substitution in children].

PMID- 16634189
TI  - [Please no pricking! Injection fear in children].

PMID- 16634190
TI  - [Do pediatric nurses and caregivers need a specialty society?].

PMID- 16634191
TI  - [Comment on the article "German Society of Pediatric Nursing e. V. is
      established" by Andreas Kray, kks 2/2006, p. 50. ].

PMID- 16634193
TI  - [Resolution of the Society of Nursing Delegates Congress of the Society of German
      Midwives, November 2005, in Berlin].

PMID- 16634192
TI  - [Bird flu--risk of infection by eating poultry products?].

PMID- 16634194
TI  - [Gathering strength, creating the future: nursing schools as network].

PMID- 16634195
TI  - ["Breast feeding promotion" becomes "baby promotion"].

PMID- 16634196
TI  - [Evolutionary reorganizations of ontogenesis in ascidians of the genus Molgula].
AB  - The data on comparative, experimental, and molecular embryology of ascidians
      (genus Molgula) published during the last 15 years have been reviewed. Some
      representatives of this genus evolved from development with a tailed larva
      (tadpole) to direct development associated with the loss of larval structures,
      such as tail, notochord, sensory organs, and differentiated muscles. The data on
      evolutionary reorganizations of ontogenesis in ascidians of the genus Molgula
      have been compared with those in sea urchins, anuran amphibians, and some other
      organisms.

PMID- 16634197
TI  - [Development of the prototroch in embryogenesis of Nereis virens (Polychaeta)].
AB  - Prototroch formation was studied in the polychaete Nereis virens using light,
      scanning electron, and confocal laser microscopy. Cell lineage of trochoblasts
      was followed and chronology of their appearance was determined. The prototroch
      ciliary ring is formed by twelve descendants of micromere lm(2). The remaining
      four primary trochoblasts have no cilia and, together with descendants of
      accessory trochoblasts, become anterior supporting cells of the prototroch.
      Posterior supporting cells are formed by secondary trochoblasts, which are
      derived from the second micromere quartet 2m. The results obtained make it
      possible to analyze one of the ancient programs of animal development.

PMID- 16634198
TI  - [Kinetics of the reaction of yolk cell surface in the loach to puncture and
      mechanic deformation].
AB  - Circumferential and radial components of the yolk cell surface movements were
      measured in the loach embryos at the late blastula stage within 40-50 min after
      puncture or indentation by an obliquely directed glass rod. The yolk cell surface
      was preliminarily marked by coal particles. It was shown that even closely
      located regions of the surface differed markedly in the rate and direction of
      their movements. In the vicinity of puncture, the yolk cell surface at first
      contracted in both circumferential and radial directions and then widened, but
      did not reach the initial values. In more remote areas, this surface continued to
      contract in the circumferential direction, but was extended in the radial
      direction. The degree of its contraction along different radii was unequal. The
      reaction to oblique indentation was anisotropic: the closest area of the yolk
      cell surface, located along the direction of indentation, contracted in both
      circumferential and radial directions and formed a fold "leaking" onto the rod,
      while the opposite area contracted in the circumferential direction, but extended
      in the radial direction. A conclusion was drawn that the yolk cell surface is a
      multivariant mechanosensitive system. Its active responses to mechanical
      influences obey the same patterns as multicellular embryonic tissues.

PMID- 16634199
TI  - [Analysis of transfer of microinjected zygotes in production of transgenic mice].
AB  - The data on transfer of mouse eggs microinjected with DNA during production of
      transgenic mice were analyzed. The transfer of mouse eggs into both oviducts did
      not lead to a reliably higher birth rate. It did not affect the frequency of
      recipients' pregnancy and, although somewhat increased the frequency of multiple
      birth, led, finally, to unjustified loss of the major part of viable DNA-injected
      eggs. We recommend transferring no less than 15 microinjected eggs only in one
      oviduct of each recipient. The transfer into another oviduct is acceptable if the
      transfer into the first oviduct failed or its outcome is doubtful.

PMID- 16634200
TI  - [Mechanics of growth pulsations as the basis of growth and morphogenesis in
      colonial hydroids].
AB  - Growth and shaping in colonial hydroids (Hydrozoa, Cnidaria) are realized due to
      the functioning of special colony elements, growing tips located at the
      terminuses of branched colony body. Unlike in plants, the growing tips of
      colonial hydroids are sites of active cell movements related to morphogenesis and
      lacking proliferation. The activity of hydroid growing tips is expressed as
      growth pulsations: cyclic repetitions of their apex extensions and retractions.
      The parameters of growth pulsations are species specific and related to the shape
      of a forming element. Here, the succession of cell movements and changes in
      mutual arrangement within the growing tip are described in detail at all
      pulsation phases. The role of the inner cell layer in the tip activity was
      demonstrated for the first time. Relationships between the growing tip
      parameters, length and diameter, and pulsations are discussed. A scheme is
      proposed for cyclic processes in both epithelial layers. An explanation is
      provided for the two-step mode of growth pulsations with relative independence of
      the main phases. It was proposed that successive activities of the tip ecto- and
      endoderm serve as driving forces provided there is a hard outer skeleton. This
      scheme makes it possible to explain some patterns of growth and morphogenesis in
      colonial hydroids, such as gradually increasing growth rate of a new tip and its
      maximum growth rate, differences in the parameters of growth pulsations between
      shoot and stolon tips, shoot base inclination towards the stolon tip, etc., and
      provides a basis for further improvement of the model of morphogenesis in
      hydroids.

PMID- 16634201
TI  - [Asexual reproduction of planarians: metric studies].
AB  - A relationship was studied between fission and restoration of body and its
      individual parts under different experimental conditions in planarians of the
      Dugesia tigrina asexual race. The body and its fragments were studied
      morphomterically. After fission, the growth of planarians demonstrated
      topographic differences. The separated tail fragments and postpharyngeal area, in
      which the zone of fission is formed, were growing at the highest rate. More
      active growth was also noted over the long body axis. Fission and growth were
      more active in isolated planarians, as compared to those kept in groups.

PMID- 16634202
TI  - [Regeneration of photoreceptor organs in freshwater planarians at different
      levels of accumulation of natural methylmercury compounds].
AB  - The effects of natural methylmercury compounds on regeneration of photoreceptor
      organs were studied in three freshwater planarians: Polycelis tenuis, Dugesia
      lugubris, and D. tigrina. Accumulation of methyl mercury in the planarian body
      suppressed regeneration of P. tenuis with numerous photoreceptor organs to a
      greater extent than in two other planarians that have only two eyes. High methyl
      mercury concentrations inhibited the restoration of photoreceptor organs in
      asexual and sexual D. tigrina races.

PMID- 16634203
TI  - [Two types of metabolic regulation of phenol oxidase activity in ontogenesis of
      house fly].
AB  - Changes of the tyrosinase activity in ontogenesis of the house fly Musca
      domestica were shown to be phase-specific and ontogenetic changes of tyrosinase
      and dihydroxyphenylalanine oxidase activities proved to be coordinated. Ascorbic
      acid stimulated some ontogenetic stages of the house fly and physiological
      indices, such as fertility, survival at different stages, and weight of puparia.
      Also, ascorbic acid modulated the tyrosinase activity.

PMID- 16634204
TI  - [Sergei G. Kryzhanovsky (1891-1961)].
AB  - This essay about the outstanding Russian embryologist and ichthyologist is not
      time to any date of his life. The cause for its appearance was an unexpected
      meeting with Elena N. Disler, whom I did not see almost 60 years. When I worked
      at the Biological Station "Glubokoe ozero" (Deep Lake), there were also
      biologists N.N. Disler and his wife E.F. Eremeeva with their children Lena and
      Vitya. At the same time, as usual, S.G. Kryzhanovsky worked at the station, who
      lived in Moscow in the same apartment with the Dislers. After the death of this
      lone scientists, his archive, mostly epistolary, was in the care of the Dislers.
      And Elena N. Disler (that girl Lena) proposed for me to have a look at this
      archive.

PMID- 16634205
TI  - [Non penetrating cardiac trauma].
AB  - Traffic accidents are a very important leading cause of death in young adults in
      our country and the most cause of non penetrating cardiac trauma. Cardiac
      contusions represent the most common form of non penetrating cardiac trauma but a
      wide spectrum of cardiac injury ranging from, cardiac valve is not usually
      foremost in the minds of physicians dealing with acutely injured patients because
      initial screening is usually focused on others classic and common injuries. There
      is actually no controversies surrounding the fact that tnsoesophageal
      echocardiography is becoming the corner stone and the most useful modality of the
      evaluation of severe chest trauma with suspicion of cardiac injury. This paper
      describe the most important blunt cardiac injuries and emphasizes indirectly the
      need for early diagnosis that becomes an easy one, if the physician keeps in mind
      such a possibility in all traumatised patients. Another concern is to point out
      the importance of appropriate therapeutic approach that may significantly improve
      outcomes in patients with blunt cardiac trauma.

PMID- 16634206
TI  - [Late post-operative adhesive small bowel occlusions. About 258 cases].
AB  - This retrospective study reports a series of 258 patients operated on for late
      developing post-operative adhesive occlusions. The impact of anterior
      interventions on these occlusions. The impact of anterior interventions on the
      occllusions as well as he clinical and paraclinical patterns are discussed before
      any approach to the different therapeutic aspects of this complication. Previous
      surgery had an impact not by number of the operations performed (80% of patient
      had undergone only one intervention on the pelvis or abdomen) but essentially by
      the nature of the opertions since most of the adhesions occured following surgery
      on the appendix. The diagnosis should be made urgently ont basis of findings
      yielded by physical examination and plain abdominal x-rays (ct-scan of the
      abdomen is hardly indicated for the absence of hydroaeric levels on the plain
      abdominal film does not defintely exclude the strangulation). Laparoscopic
      adhesiolys is an adegnate treatment in case of a single adhesion. This
      laparoscopic is an adegnate treatment in case of a single adhesion. This
      laparoscopic procedure practised on 11 patients had to be transformed in 3 cases
      in to an open laparoctomy. Resection rate was 11.6%. Mortality and morbidity
      rates were 2% and 17% respectively.

PMID- 16634207
TI  - [Indicators for successful vaginal delivery after cesarean section: a proposal of
      a predictive score].
AB  - The purpose of this study is to determine predictive factors of successful
      vaginal delivery after cesarean section, and to estimate the risks of this trial
      of labor (TOL). A retrospective study about 352 women undergoing a TOL after
      cesarean section was carried out. Different variables stratified by the
      termination of the TOL were analysed with statistic tests. TOL success rate was
      76.1%. Parity > or = 3. prior vaginal delivery following cesarean section, body
      mass index < 30, fundal height < 34 cm, and low fetal head level at the beginning
      of labor increased significantly the probability of success. Uterine rupture rate
      is 1.1%. Failure of TOL was associated with a higher risk of uterine scar
      dehiscence and rupture, and higher fetal morbidity. A predictive score of
      successful vaginal delivery after cesarean section is proposed.

PMID- 16634208
TI  - [Use of Hoffman external fixation for extra-articular upper metaphysealtibial
      fractures].
AB  - Treatment of extra-articular upper metaphyseal tibial fractures can be difficult.
      Orthopedic treatment is frequently complicated by second displacement These
      fractures are inappropriate for locked intra-medullary nailing because of the
      shorteness of the proximal extremity. Damages of soft tissues. frequently
      associated with these factures, expose internal osteosynthesis to many risks. For
      these reasons, we opted for external fixation. Our study was a retrospective
      analysis of 46 extra-articular metaphyseal tibial fractures treated by external
      fixation with Hoffman material. The average follow-up was 24 months.
      Consolidation was obtained within 4 months in average. Septic complications.
      inherent to the method were uncommon or minor. Functional results were
      satisfactory in 84% of cases. So, external fixation with Hoffman material. with
      particular recommandations, is a promising method for the treatment of extra
      articular of proximal metaphyseal tibial fractures.

PMID- 16634209
TI  - [Gastrointestinal stromal tumor: epidemiology and outcome study in 40 cases].
AB  - The aim of this study was to analyze epidemiology and outcome of 40 patients with
      gastrointestinal stromal tumor (GIST) expressed CD 117. All epidemiological data
      (age, sex, location) and survival data were analyzed retrospectively. The tumors
      occurred in 17 men and 23 women. Stomach was the most common site of localization
      (47.5%). Of the 37 patients without Gleevec treatment, 18 benignant cases (66.6%)
      showed long-term survival (2 to 8 years) and 9 malignant cases (33.3%) were
      diagnosed. 10 cases were still being in followed (< 2 years). Gastric tumor's
      survival was better than extragastric tumor's survival without statistically
      significance (p>0.05). Our experience confirms that GIST is an aggressive tumor.
      33.33% of them are malignant with recurrence or metastatic potential.
      Additionnally, epidemiologic factors (age, sex and location) do not have a
      predictive value.

PMID- 16634210
TI  - [Occupational cancer in Tunisia].
AB  - Occupational cancers are cancers due to the exposition of the worker during his
      daily work to a carcinogenic agent. In Tunisia. the number of declared and
      compensate cases is still low. The aim of this study is to asses the role of
      occupational agents in the development of bronchial and pleural cancers and to
      discuss the causes of this under-assessment. METHODS AND MATERIAL: The
      occupational history of 107 patients with bronchial and pleural cancer was
      prospectively collected between Jun 2001 and July 2002. A detailed list of the
      possible occupational activities that would expose the worker to a carcinogenic
      agent incriminated in the genesis of bronchial or pleural carcinoma was used.
      RESULTS: Seven cases among 107 bronchial and pleural cancers were thought to have
      a occupational origin (6.5%). Two patients had pleural mesothelioma due to an
      exposition to asbestos in the field of navy constructions and building. The 5
      remaining patients had bronchial carcinomas of different histological types (3
      squamous cell carcinoma, 1 adenocarcinoma and 1 small cell carcinoma). The
      suspected agents were Arsenic in 4/5 cases in fields of metallurgy (2 cases),
      mine digging (1 cases), agriculture (1 case). In 1/5 case the suspected agent was
      asbestos in brake- plates' maintenance in big engines. The mean duration of the
      exposition was 22 years and the latency period was 26 years. CONCLUSION: The role
      of occupational agents in the development of bronchial and pleural cancer is
      important but not routinely assessed.

PMID- 16634211
TI  - [Hospital solid waste: quantification. Bacteriological analyses--case of hospital
      Ibn Sina].
AB  - Hospital waste represent, by their nature and their constitution, a big threat to
      health in the intra and extra hospital area. and a source of pollution for the
      environment. A 12-day campaign of weighing of the waste produced by the hospital
      Ibn Sina of Rabat-Morocco should an average of 1.75 kg/bed/day. In order to
      identify the hospital pathogenic germs as well as their sensitivities to
      antibiotics, some bacteriological analyses have been done on the percolat waste
      of this hospital. The results of these analyses put in evidence the presence of
      Pseudomonas aeruginosa and Staphylococcus aureus and their resistance to some
      antibiotics.

PMID- 16634212
TI  - [Anomalous origin of coronary arteries from the aorta].
AB  - The authors report the series of 9 patients (6 male and 3 female, aged from 32 to
      64 years) with anomalous origin of coronary arteries from the aorta discovered at
      coronary arteriography. In 4 cases, the circumflex, artery aries from the right
      coronary sinus and in 5 cases, the right coronary artery arises from the left
      coronary sinus. Severe atherosclerotic coronary disease was discovered in 5
      cases. We conclude that aberrant coronary origin from the aorta is a rare
      congenital anomalous discovered usually at coronary angiography and certain
      patients with this anomalous can develop severe myocardial ischemia especially
      when a vessel runs between the aorta and pulmonary artery.

PMID- 16634213
TI  - [Prenatal diagnosis of omphalocele: a report of four cases].
AB  - Fetal omphalocele is a congenital midline defect of the ventral abdominal wall
      with herniation of abdominal contents into the base of ombilical cord. The
      prenatal diagnosis of omphalocele by real-time sonography is important for
      intrauterine and neonatal management and prognosis. The prognosis and mortality
      rate is determined rather by the presence of serious associated anomalies, such
      as cardiovascular and chromosomal defects, than by the omphalocele itself. MRI
      should be used to screen for other associated anomalies. In this report we
      describe four cases of fetal omphalocele diagnosed by sonography. In one case an
      MR examination was performed for suspected associated nervous anomalies. Prenatal
      literature is further reviewed to assess the clinical significance of this
      finding.

PMID- 16634214
TI  - [Nasosinusal sarcoidosis: 2 cases. A report of 2 cases].
AB  - INTRODUCTION: Nasosinusal sarcoidosis is a rare non caseating granulomatous
      disease. It may be inaugural, isolated or associated with multisystemic
      sarcoidosis. MATERIAL AND METHODS: [corrected] We report two cases of nasosinusal
      sarcoidosis associated to multisystemic sarcoidosis. Both patients were females
      aged over 43 years. In one case, the primary symptom was a nasal obstruction.
      Tomodensitometric and guided biopsy findings provided the main diagnostic
      criteria. Anti-malaric treatment was prescibed in both cases. Stabilisation of
      the lesions was noted. DISCUSSION: we tried to reveal through this study the
      diagnostic an therapeutic difficulties of nasosinusal sarcoidosis.

PMID- 16634215
TI  - [Management of serious renal trauma. About 2 cases].
AB  - Management of serious stage 3 of Chatelain renal trauma has advanced, due to the
      development of radiologic investigation techniques, towards a less surgical
      attitude. We report two cases of serious stage 3 renal traum. In spite of the
      importance of the parenchymal injuries revealed by CT scan, it was decided not to
      resort to surgery. The clinical course was good, and repeated Ct scan controls
      showed nearly completely healed injuries. Surgery shouldn't be recommended in
      case of stage 3 blunt renal trauma in patients hemodynamically stable or
      stabilized.

PMID- 16634216
TI  - [Fetal cystic hygroma antenatal diagnosis. Prognosis and management].
AB  - Fetal cystic hygroma is a rare congenital malformation. The incidence of this
      pathology is 1/700 pregnancies. This malformation can be seen at antenatal
      ultrasonography from the end of the first trimester of pregnancy. The prognosis
      depends on chromosome analysis, other ultrasound abnormality and the size of the
      fetal cystic hygroma. Starting from a case diagnosed in the prenatal follow up
      and from litterature review, the authors discusse the ultrasound diagnosis,
      prognosis and management of this malformation.

PMID- 16634217
TI  - [Benign schwannoma: a case report about a uncommon localisation].
AB  - Schwannoma is a benign slow growing nerve sheath tumor which generally originates
      from cranial or spinal nerve roots. Peripheral nerve localisations are scarce. We
      report the case of a 76-year man who presented with a laterosternal chest wall
      mass located in the fourth intercostal space. Diagnosis of intercostal benign
      schwannoma was suggested by medical imaging and confirmed histologicolly upon
      surgical removal. Chest wall solitary schwannoma is exceptional. Our case is
      still more interesting by its peripheral localisation and late occurence
      following a chest trauma.

PMID- 16634218
TI  - [Association lichen planus and ulcerative colitis. A case report].
AB  - Ulcerative colitis is a frequent chronic inflammatory boxel disease. Its
      cutaneous manifestation are varied. Some of them are frequent like pyoderma
      gangrenosum, erethema nodosum and oral ulceration. We report the case of an
      exceptional association of ulcerative colitis with lichen planus in a 40-year old
      woman with a 2 year history of ulcerative colitis, who had lesions on the buccal
      mucosa and the lower lip for which the diagnosis of lichen planus was made and
      confirmed histologically.

PMID- 16634219
TI  - Bridging the gap between researchers and policy-makers: international
      collaboration through the biosafety clearing-house.

PMID- 16634220
TI  - Tiered tests to assess the environmental risk of fitness changes in hybrids
      between transgenic crops and wild relatives: the example of virus resistant
      Brassica napus.
AB  - Over the last 20 years, there has been much research aimed at improving
      environmental risk assessment of transgenic crops. Despite large amounts of data,
      decisions to allow or prohibit the release of transgenic crops remain confused
      and controversial. We argue that part of the reason for confusion is the lack of
      clear definitions of components of the environment that should be protected, and,
      as a consequence, there is no way to judge the relevance of data collected under
      the auspices of 'environmental risk assessment'. Although this criticism applies
      to most aspects of environmental risk assessment of transgenic crops, it is most
      pertinent to effects that might result from an increase in plant fitness, often
      referred to as increased weediness. Environmental risk assessment of weediness is
      regarded as complicated: an increase in the fitness of a transgenic plant
      compared with non-transgenic counterparts will be the result of an interaction
      between the altered plant phenotype and an enormous number of environmental
      variables. This has led to the idea that risk assessment of weediness needs to
      "understand" these interactions, with the implication that exhaustive data are
      required. Here we argue that environmental risk assessment of the weediness of
      transgenic plants need not be complicated. Analysis of the conditions that must
      be met for increased weediness to occur suggests a series of studies that starts
      with simple tests in the laboratory under "worst case" assumptions, and becomes
      increasingly complex and realistic should the simpler studies not indicate
      negligible risk with sufficient certainty. We illustrate how the approach might
      work for assessing the risks of increased weediness using the example of possible
      introgression of a gene for Turnip mosaic virus (TuMV) resistance from oilseed
      rape to certain wild Brassica species.

PMID- 16634221
TI  - Understanding the potential impact of transgenic crops in traditional
      agriculture: maize farmers' perspectives in Cuba, Guatemala and Mexico.
AB  - Genetically engineered transgenic crop varieties (TGVs) have spread rapidly in
      the last 10 years, increasingly to traditionally-based agricultural systems
      (TBAS) of the Third World both as seed and food. Proponents claim they are key to
      reducing hunger and negative environmental impacts of agriculture. Opponents
      claim they will have the opposite effect. The risk management process (RMP) is
      the primary way in which TGVs are regulated in the US (and many other industrial
      countries), and proponents claim that the findings of that process in the US and
      its regulatory consequences should be extended to TBAS. However, TBAS differ in
      important ways from industrial agriculture, so TGVs could have different effects
      in TBAS, and farmers there may evaluate risks and benefits differently. To
      evaluate some potential impacts of TGVs in TBAS we used the RMP as a framework
      for the case of Bt maize in Mesoamerica and Cuba. We interviewed 334 farmers in
      Cuba, Guatemala and Mexico about farming practices, evaluations of potential harm
      via hypothetical scenarios, and ranking of maize types. Results suggest high
      potential for transgene flow via seed, grain and pollen; differences in effects
      of this exposure in TBAS compared with industrial agriculture; farmers see some
      potential consequences as harmful. Perceptions of harm differ among farmers in
      ways determined by their farming systems, and are different from those commonly
      assumed in industrial systems. An RMP including participation of farmers and
      characteristics of TBAS critical for their functioning is necessary to ensure
      that investments in agricultural technologies will improve, not compromise these
      agricultural systems.

PMID- 16634222
TI  - Persistence of Agrobacterium tumefaciens in transformed conifers.
AB  - Previous studies have shown that the widely used plant transformation vector
      Agrobacterium tumefaciens can persist in genetically engineered plants in vitro
      and in transgenic greenhouse-grown plants, despite the use of counter-selective
      antibiotics. However, little is known regarding Agrobacterium persistence in tree
      species. To understand the kinetics of A. tumefaciens decline and persistence in
      transformation experiments, we assayed for the presence of A. tumefaciens in
      spruce and pine embryogenic tissue for up to 10 weeks post-transformation. The A.
      tumefaciens populations declined rapidly in the first five days post
      cocultivation but generally declined more slowly in pine, relative to spruce. No
      bacteria were detected in spruce embryogenic tissue beyond four weeks after
      cocultivation, however in pine there were -100 colony forming units per g tissue
      at 10 weeks post-cocultivation. We present evidence that the detection limit for
      PCR using virD2 primers to detect A. tumefaciens in a background of pine needle
      DNA was approximately 10(9)-10(10) A. tumefaciens cells per g of tissue. We also
      assayed for A. tumefaciens in transgenic pine and spruce embryogenic tissue and
      from needles, branches, stems and roots of transformed plants, up to four years
      post-inoculation. Occasionally A. tumefaciens was detected in embryogenic tissue
      up to 12 months post-inoculation. A. tumefaciens was never detected in cultured
      embryogenic tissue more than twelve months after inoculation, nor in developing
      somatic embryos or germinating plantlets, nor any of the parts of greenhouse
      grown plants. From these data we conclude that if A. tumefaciens persists in
      transgenic conifers, it does so beneath our ability to detect it.

PMID- 16634223
TI  - Potential adoption and management of insect-resistant potato in Peru, and
      implications for genetically engineered potato.
AB  - This paper analyzes some important issues surrounding possible deployment of
      genetically engineered (GE) insect-resistant potato in Peru, based on a large
      farmer survey held in Peru in 2003. We found that the formal seed system plays a
      limited role compared with the informal seed system, especially for smallholder
      farmers. Although 97% of smallholder farmers would buy seed of an insect
      resistant variety, a majority would buy it only once every 2 to 4 years. Survey
      data show that farmers would be willing to pay a premium of 50% on seed cost for
      insect resistant varieties. Paying price premiums of 25% to 50%, farmers would
      still increase their net income, assuming insect resistance is high and pesticide
      use will be strongly reduced. Of all farmers, 55% indicated preference for insect
      resistant potato in varieties other than their current varieties. The survey
      indicates that smallholder farmers are interested to experiment with new
      varieties and have a positive perception of improved varieties. Based on these
      findings, and considering the difficulties implementing existing biosafety
      regulatory systems such as those in place in the U.S. and E.U., we propose to
      develop a variety-based segregation system to separate GE from conventionally
      bred potatoes. In such a system, which would embrace the spread of GE potatoes
      through informal seed systems, only a limited number of sterile varieties would
      be introduced that are easily distinguishable from conventional varieties.

PMID- 16634224
TI  - Hydrogen from organic waste: a bioprocess challenge for the next decade.

PMID- 16634225
TI  - Integrating multi-criteria techniques with geographical information systems in
      waste facility location to enhance public participation.
AB  - Despite recent U.K. Government commitments' to encourage public participation in
      environmental decision making, those exercises conducted to date have been
      largely confined to 'traditional' modes of participation such as the
      dissemination of information and in encouraging feedback on proposals through,
      for example, questionnaires or surveys. It is the premise of this paper that
      participative approaches that use IT-based methods, based on combined
      geographical information systems (GIS) and multi-criteria evaluation techniques
      that could involve the public in the decision-making process, have the potential
      to build consensus and reduce disputes and conflicts such as those arising from
      the siting of different types of waste facilities. The potential of these
      techniques are documented through a review of the existing literature in order to
      highlight the opportunities and challenges facing decision makers in increasing
      the involvement of the public at different stages of the waste facility
      management process. It is concluded that there are important lessons to be
      learned by researchers, consultants, managers and decision makers if barriers
      hindering the wider use of such techniques are to be overcome.

PMID- 16634226
TI  - Recovery of copper and cobalt from ancient slag.
AB  - About 2.5 million tonnes of copper smelter slag are available in Kure, northern
      part of Turkey. This slag contains large amounts of metallic values such as
      copper and cobalt. A representative slag sample containing 0.98% Cu, 0.49% Co and
      51.47% Fe was used in the experimental studies. Two different methods, direct
      acid leaching and acid baking followed by hot water leaching were used for
      recovering Cu and Co from the slag. The effects of leaching time, temperature and
      acid concentration on Cu- and Co-dissolving efficiencies were investigated in the
      direct acid leaching tests. The optimum leaching conditions were found to be a
      leaching time of 2 h, acid concentration of 120 g L(-1), and temperature of 60
      degrees C. Under these conditions, 78% Cu and 90% Co were extracted. In the acid
      baking + hot water leaching tests, 74% Co was dissolved after 1 h of roasting at
      200 degrees C using a 3:1 acid:slag ratio, whereas the Cu-dissolving efficiency
      was 79% and the total slag weight loss was approximately 50%.

PMID- 16634227
TI  - Production of brown and black pigments by using flotation waste from copper slag.
AB  - One of the major problems in copper-producing countries is the treatment of the
      large amount of copper slag or copper flotation waste generated from copper slag
      which contains significant amounts of heavy metals such as Cu, Zn, Pb and Co.
      Dumping or disposal of such large quantities of flotation waste from copper slag
      causes environmental and space problems. In this study, the treatment of
      flotation waste from copper slag by a thermal method and its use as an iron
      source in the production of inorganic brown and black pigments that are used in
      the ceramic industry were investigated. The pigments were produced by calcining
      different amounts of flotation waste and chromite, Cr2O3, ZnO and CoO mixtures.
      The pigments obtained were added to transparent ceramic glazes and porcelainized
      tile bodies. Their colours were defined by L*a*b* measurements with a
      spectrophotometer. The results showed that flotation waste from copper slag could
      be used as an iron source to produce brown and black pigments in both ceramic
      body and glazes.

PMID- 16634228
TI  - Leaching of heavy metals in acid mine drainage.
AB  - Acid mine drainage is one of the most serious environmental problems that the
      coal and metal mining industry is currently facing. The generation of low pH
      drainage enhances the dissolution of heavy metals in water. The samples used in
      this research originated from three pits at mine dumps. In a study reported in
      this paper, three types of tests; namely static test, kinetic test and column
      test were conducted to estimate acid generation and acid neutralization reaction
      rates, and to predict the solubility of metals and their release rates. Static
      test showed that all samples had a pH of net acid generation (NAG pH) <4, a net
      acid producing potential (NAPP) >10 kg H2SO4tonne(-1), and a S-content >3%, which
      can be classified as a high acid-forming capacity. Simulated runoff in the column
      tests was equivalent to 5-year average rainfall in Indonesia, the resultant
      leachates showed acidic behaviour (pH < 3.5). Based on the results, it was found
      that high mobilization of heavy metals (Cr, Cu, Zn, Cd and Pb) takes place under
      strong acidic conditions (pH approximately equal 2).

PMID- 16634229
TI  - Environmental modelling of use of treated organic waste on agricultural land: a
      comparison of existing models for life cycle assessment of waste systems.
AB  - Modelling of environmental impacts from the application of treated organic
      municipal solid waste (MSW) in agriculture differs widely between different
      models for environmental assessment of waste systems. In this comparative study
      five models were examined concerning quantification and impact assessment of
      environmental effects from land application of treated organic MSW: DST (Decision
      Support Tool, USA), IWM (Integrated Waste Management, U.K.), THE IFEU PROJECT
      (Germany), ORWARE (ORganic WAste REsearch, Sweden) and EASEWASTE (Environmental
      Assessment of Solid Waste Systems and Technologies, Denmark). DST and IWM are
      life cycle inventory (LCI) models, thus not performing actual impact assessment.
      The DST model includes only one water emission (biological oxygen demand) from
      compost leaching in the results and IWM considers only air emissions from avoided
      production of commercial fertilizers. THE IFEU PROJECT, ORWARE and EASEWASTE are
      life cycle assessment (LCA) models containing more detailed land application
      modules. A case study estimating the environmental impacts from land application
      of 1 ton of composted source sorted organic household waste was performed to
      compare the results from the different models and investigate the origin of any
      difference in type or magnitude of the results. The contributions from the LCI
      models were limited and did not depend on waste composition or local agricultural
      conditions. The three LCA models use the same overall approach for quantifying
      the impacts of the system. However, due to slightly different assumptions,
      quantification methods and environmental impact assessment, the obtained results
      varied clearly between the models. Furthermore, local conditions (e.g. soil type,
      farm type, climate and legal regulation) and waste composition strongly
      influenced the results of the environmental assessment.

PMID- 16634230
TI  - Life cycle modelling of environmental impacts of application of processed organic
      municipal solid waste on agricultural land (EASEWASTE).
AB  - A model capable of quantifying the potential environmental impacts of
      agricultural application of composted or anaerobically digested source-separated
      organic municipal solid waste (MSW) is presented. In addition to the direct
      impacts, the model accounts for savings by avoiding the production and use of
      commercial fertilizers. The model is part of a larger model, Environmental
      Assessment of Solid Waste Systems and Technology (EASEWASTE), developed as a
      decision-support model, focusing on assessment of alternative waste management
      options. The environmental impacts of the land application of processed organic
      waste are quantified by emission coefficients referring to the composition of the
      processed waste and related to specific crop rotation as well as soil type. The
      model contains several default parameters based on literature data, field
      experiments and modelling by the agro-ecosystem model, Daisy. All data can be
      modified by the user allowing application of the model to other situations. A
      case study including four scenarios was performed to illustrate the use of the
      model. One tonne of nitrogen in composted and anaerobically digested MSW was
      applied as fertilizer to loamy and sandy soil at a plant farm in western Denmark.
      Application of the processed organic waste mainly affected the environmental
      impact categories global warming (0.4-0.7 PE), acidification (-0.06 (saving)-1.6
      PE), nutrient enrichment (-1.0 (saving)-3.1 PE), and toxicity. The main
      contributors to these categories were nitrous oxide formation (global warming),
      ammonia volatilization (acidification and nutrient enrichment), nitrate losses
      (nutrient enrichment and groundwater contamination), and heavy metal input to
      soil (toxicity potentials). The local agricultural conditions as well as the
      composition of the processed MSW showed large influence on the environmental
      impacts. A range of benefits, mainly related to improved soil quality from long
      term application of the processed organic waste, could not be generally
      quantified with respect to the chosen life cycle assessment impact categories and
      were therefore not included in the model. These effects should be considered in
      conjunction with the results of the life cycle assessment.

PMID- 16634231
TI  - Evaluation of bangkok sewage sludge for possible agricultural use.
AB  - Bangkok (Thailand) covers more than 1500 km2 and has 10 million inhabitants. The
      disposal of wastewater is creating huge problems of pollution. The estimated
      amount of sewage sludge was estimated to be around 108 tonnes dry matter (DM) per
      day in 2005. In order to find a lasting way of disposal for this sewage sludge,
      the suitability of the sludge produced from three waste-water treatment plants
      for use as fertilizing material was investigated. Monthly samplings and analysis
      of sewage sludge from each plant showed that the composition of sludge varied
      according to the area of collection and period of sampling, and there was no link
      to rainfall cycle. Plant nutrient content was high (i.e. total N from 19 to 38 g
      kg(-1) DM) whereas organic matter content was low. The concentrations of heavy
      metals varied between sludge samples, and were sometimes higher than the E.U. or
      U.S. regulations for sewage sludge use in agriculture. Faecal coliforms were
      present in the sludge from one of the plants, indicating a possible contamination
      by night soil. In order to decrease this potentially pathogenic population the
      sewage sludge should be heated by composting. As the C/N ratio of sewage sludge
      was low (around 6) some organic by-products with high carbon content could be
      added as structural material to enhance the composting.

PMID- 16634232
TI  - Nitrogen mineralization and nitrate leaching of a sandy soil amended with
      different organic wastes.
AB  - Organic wastes can be recycled as a source of plant nutrients, enhancing crop
      production by improving soil quality. However, the study of the dynamic of soil
      nutrient, especially the N dynamic, after soil application of any organic
      material is vital for assessing a correct and effective use of the material,
      minimizing the losses of nitrate in leachates and avoiding the negative
      environmental effects that it may cause in groundwater. To estimate the effect of
      three organic materials, a municipal solid waste compost (MWC), a non-composted
      paper mill sludge (PS), and an agroforest compost (AC) on the N dynamic of a
      sandy soil two experiments were carried out: an incubation experiment and a
      column experiment. The incubation experiment was conducted to estimate the N
      mineralization rate of the different soil-amendment mixtures. The soil was mixed
      with the organic amendments at a rate equivalent to 50,000 kg ha(-1) and
      incubated during 40 weeks at constant moisture content (70% of its water-holding
      capacity) and temperature (28 degrees C) under aerobic conditions. Organic
      amendment-soil samples showed an immobilization of N during the first weeks,
      which was more noticeable and longer in the case of PS-treated soil compared to
      the other two amendments due to its high C/N ratio. After this immobilization
      stage, a positive mineralization was observed for all treatment, especially in
      MWC treated soil. Contemporaneously a 1-year column (19 cm diameter and 60 cm
      height) experiment was carried out to estimate the nitrate losses from the soil
      amended with the same organic materials. Amendments were mixed with the top soil
      (0-15 cm) at a rate equivalent to 50,000 kg ha(-1). The columns were periodically
      irrigated simulating rainfall in the area of study, receiving in total 415 mm of
      water, and the water draining was collected during the experimental period and
      analysed for NO3-N. At the end of the experimental period NO3-N content in soil
      columns at three depths (0-20, 20-35 and 35-50 cm) was determined. The nitrate
      concentration in drainage water confirmed the results obtained in the incubation
      experiment: nitrate leaching was higher in soil treated with MWC due to its
      higher N-mineralization rate. Nevertheless, the nitrate losses represented a low
      amount compared with the total nitrogen added to soil. No clear signs of water
      draining contamination were observed during the first year after the application
      of AC and PS; however, the nitrate leaching in soil treated with MWC slightly
      exceeded the limit allowed for the Drinking Water Directive 98/83/CE.

PMID- 16634233
TI  - The performance of a natural treatment system for landfill leachate with special
      emphasis on the fate of organic pollutants.
AB  - A natural treatment system for the treatment of leachate was studied at Moskogen
      landfill in southern Sweden. This facility consists of three consecutive ponds
      and a soil-plant (SP)-system. A test area, receiving water from the third pond
      with the same hydraulic load as the SP-system, was used for estimation of the
      latter system. Quality parameters including biochemical oxygen demand, total
      organic carbon, ammonium, nitrate, orthophosphate, and total suspended solids
      along the treatment line were determined as well as soluble metals (Cu, Cd, Zn,
      Cr, Ni, and Pb). In addition a thorough investigation along the treatment line
      has also been performed concerning volatile organic compounds and semi-volatile
      organic compounds. Non-polar organic compounds were investigated using gas
      chromatography-mass spectrometry. Quantification was based on the assumption of
      equal response for the compounds found in comparison with the chosen marker
      substances. For polar, water-soluble compounds the measurements were restricted
      to phenolic compounds using high-performance liquid chromatography. Several
      different types of organic compounds were found in the raw leachate including
      aromatics, benzene-sulfonamides, biphenyls, naphthalene, organic phosphates,
      polycyclic aromatic hydrocarbons, polychlorinated biphenyls, phenols and
      phthalates. The treatment system efficiently reduced organic pollutants, heavy
      metals, and nitrogen/phosphorous compounds. Most metals and organic compounds in
      the leachate were already significantly reduced to a low level in the treatment
      ponds and ammonium-N was efficiently transformed to nitrate-N in the SP-system.

PMID- 16634234
TI  - Adverse drug reaction reporting and pharmacovigilance of new therapeutic agents.

PMID- 16634235
TI  - Conversion motor paralysis disorder.

PMID- 16634236
TI  - Amiodarone-induced pulmonary hemorrhage.

PMID- 16634237
TI  - Central nervous system tuberculosis and paradoxical response.

PMID- 16634238
TI  - Age and adverse outcomes in rib fracture patients.

PMID- 16634239
TI  - Preventing heat illness in athletes.

PMID- 16634240
TI  - Adverse outcomes in younger rib fracture patients.
AB  - BACKGROUND: Recent studies on the impact of rib fractures after blunt trauma have
      shown a linear relationship between age, increasing number of rib fractures, and
      complications, including mortality. Others have documented that age-related
      morbidity increases before age 65 in trauma patients. We hypothesize that
      patients as young as age 45 demonstrate increased morbidity with injuries similar
      to older patients. METHODS: We performed a retrospective cohort study involving
      all blunt trauma patients with rib fractures, excluding those with severe head
      and abdominal injuries and those dying within 24 hours, admitted between January
      2001 and December 2004. Outcome parameters included pulmonary complications, ICU
      length of stay, hospital and ICU length of stay, Injury Severity Score (ISS),
      number of vent days, number of rib fractures, mechanism of injury, and discharge
      disposition. RESULTS: Of the 3,094 patients admitted, 307 met the inclusion
      criteria (9.9%). Based on statistical analysis of age, number of rib fractures,
      and adverse outcome variables, patients were separated into 4 groups: Group 1:
      younger than 44 years old with 1 to 4 rib fractures, Group 2: younger than 44
      years with greater than 4 rib fractures, Group 3: 45 years or older with 1 to 4
      rib fractures, and Group 4: 45 years or older with more than 4 rib fractures. Age
      groups and outcome variables were compared with chi-square, analysis of variance
      and multiple regression analysis. Respiratory failure, pneumonia, and associated
      thoracic injuries were increased in Group 4 patients compared with other groups
      (P < 0.05). Mortality and length of stay were not different between groups.
      CONCLUSIONS: Patients as young as 45 with more than 4 rib fractures are at
      increased risk for adverse outcomes. Efforts to improve outcomes in rib fracture
      patients should focus not only on elderly patients, but on those as young as 45
      years. Based on these data, we established a rib fracture clinical pathway
      focusing on patients 45 years and older with more than 4 rib fractures.

PMID- 16634241
TI  - Heat illness symptom index (HISI): a novel instrument for the assessment of heat
      illness in athletes.
AB  - BACKGROUND: Heatstroke is the third leading cause of death in athletics, and an
      important cause of morbidity and mortality in exercising athletes. There is no
      current method, however, for identifying milder forms of heat illness. In this
      pilot study, we sought to develop and provide initial validation for a Heat
      Illness Symptom Index scale (HISI) that would facilitate research in the
      assessment of milder forms of heat illness in athletes. METHODS: The study was
      designed as a multimodal prospective observational study of Division I football
      players during twice daily practices in southern Florida. We developed a 13-item
      scale that assessed symptoms that are suspected to occur during milder forms of
      heat illness. The resultant scale was assessed for reliability using Cronbach's
      alpha, and was assessed for construct validity by correlating scale scores with
      factors that are known to be related to heat illness. HISI scores, as well as
      data on perceived exertion, player position, and pre and post practice weights
      were collected from 95 athletes participating in late summer football practices.
      A total of 557 athlete sessions were analyzed. RESULTS: The mean score on the
      heat illness symptom scale was 12.1 (SD 13.8) and the median value was 8.0.
      Cronbach's alpha confirmed suitable internal consistency of the scale when
      assessed separately for each of the five morning practices (alpha = 0.91, 0.88,
      0.82, 0.92, 0.85). There were statistically significant correlations of the scale
      score with weight loss during practice (P = 0.006), rating of perceived exertion
      (P = 0.005), player position (P < 0.0001), and ambient heat index (P = 0.02) as
      hypothesized. CONCLUSIONS: This pilot study provides initial validation for a
      novel symptom-based tool for use in assessing mild forms of heat illness in an
      athletic population. Further validation studies of the instrument, and
      correlating symptom scores with measures of core temperature, are needed and
      planned.

PMID- 16634242
TI  - Pounds of cure: chart weight as a measure of service intensity.
AB  - Intensity of hospital services is often estimated by length of stay (LOS).
      Increasing demands for documentation in the medical record suggested to us an
      alternate method: weighing the chart. In a retrospective study, we compared LOS
      and chart weight as predictors of actual hospital costs at a community teaching
      hospital. We reviewed a sample of 123 patients randomly chosen from the medical
      service and stratified by phase of the academic year. Both least-squares
      regression and a multiple sampling/validating technique were used to derive mean
      cost per ounce of chart and per day of stay. Costs estimated from weight were
      within 7% and from LOS within 14% of measured actual costs among patients not
      used to derive the formulae. We conclude that the intensity of paper
      documentation closely reflects actual costs; the same may be true of bytes or key
      strokes for electronic records.

PMID- 16634243
TI  - Descriptive epidemiology of hepatitis C virus among male heroin abusers in
      Taiwan.
AB  - BACKGROUND: The purpose of this study was to explore the epidemiology of
      hepatitis C virus (HCV) infection and to determine the risk factors for HCV
      infection among heroin abusers in Taiwan. METHODS: This was a cross-sectional
      study. From November 2004 to February 2005, 577 subjects, including 423 subjects
      (73.3%) using injectable heroin and 154 subjects (26.7%) using smoked heroin from
      one male prison located in Taiwan, were enrolled in this study. The mean age was
      33.3 +/- 7.9 years (age range 19-65 years). Anti-HCV antibody was tested. A face
      to-face interview focusing on sociodemographic information and risk behaviors was
      addressed. The t test, chi-squared test, and multivariate logistic regression
      were used. RESULTS: The overall prevalence of anti-HCV antibody positivity was
      74.9%, with 89.8% among injecting heroin abusers and 33.8% among smoking heroin
      abusers (P < 0.0001). The multivariate logistic regression analysis demonstrated
      that needle sharing was independently related to HCV infection (odds ratio =
      5.25, 95% confidence interval = 2.48-11.12). CONCLUSIONS: The prevalence of anti
      HCV antibody positivity among male injecting drug abusers is high in Taiwan.
      Needle sharing is identified as a potential risk factor for HCV infection.

PMID- 16634244
TI  - Dysnatremias: why are patients still dying?
AB  - Dysnatremias are a common clinical entity that are often associated with poor
      outcomes. This review takes a case study approach to understand how dysnatremias
      can result in devastating neurologic consequences. Concrete guidelines are
      provided for prevention, early recognition and treatment along with a discussion
      of how urinary electrolytes and osmolality can be used to guide therapy. Case
      studies in hyponatremic encephalopathy include the post-operative state, thiazide
      diuretics, extreme exercise and DDAVP use. Reasons to avoid using hypotonic
      parenteral fluids, risk factors for hyponatremic encephalopathy such as age,
      gender, and hypoxia, and the appropriate use of 3% sodium chloride are discussed.
      Case studies in hypernatremia include hypernatremia in the ICU setting and the
      emerging condition of breastfeeding-associated hypernatremia in infants.

PMID- 16634245
TI  - Easy bruisability.
AB  - Physicians often see patients who complain of "easy bruising." The skill of the
      clinician is to identify those patients likely to have a potentially serious
      underlying disorder from those who do not. A detailed history often provides
      sufficient information. A comprehensive physical examination and possibly some
      baseline laboratory studies can add more data. These tools should permit the
      clinician to decide if the patient is either basically normal, may have simple
      contributing factors that lead to bruising, or is at significant risk of bleeding
      due to the presence of an underlying disorder. In certain circumstances, the
      situation will prompt the referral to a hematologist or other specialist
      (gastroenterologist, nephrologist, rheumatologist, endocrinologist, etc.).

PMID- 16634246
TI  - An unrecognized cause of recurrent hypercalcemia: immobilization.
AB  - We report a 66-year-old Chinese man with chronic renal insufficiency (creatinine
      1.7 mg/dL) and gout suffering from slurred speech and right hemiplegia for 3
      days. Acute cerebral infarction was confirmed by computed tomography. Conscious
      disturbance occurred on the tenth hospital day without significant changes on
      imaging study when compared with a previous scan. Hypercalcemia (total calcium
      14.1 mg/dL) and acute exacerbation of chronic renal failure (serum creatinine 2.5
      mg/dL) were noticed. Hypercalciuria (FECa 3.2%), and low serum levels of intact
      parathyroid hormone and 1,25(OH)2D3 suggested nonparathyroidal hypercalcemia. An
      extensive workup failed to identify any etiology of hypercalcemia. Hypercalcemia
      and renal failure were temporarily ameliorated after aggressive volume expansion
      and loop diuretic treatment but recurred 2 weeks later. Immobilization
      hypercalcemia was considered after the exclusion of other discernible causes and
      was successfully treated with rehabilitative exercises and bisphosphonates
      without further recurrence during a 2-year follow-up. Clinical alertness to
      immobilization as a possible cause of hypercalcemia may avoid unnecessary and
      invasive examinations, life-threatening complications and annoying recurrences.

PMID- 16634247
TI  - New anticonvulsants--new adverse effects.
AB  - Ongoing refinements in pharmacology continue to provide new medications for the
      treatment of seizure disorders and other neurologic conditions. The authors
      present the cases of two children who developed relatively uncommon adverse
      effects to new anticonvulsant medications, including metabolic acidosis with
      topiramate and hyponatremia with oxcarbazepine. In one of our two patients,
      intraoperative acidosis related to topiramate was noted. Appropriate
      investigation with documentation of normal serum lactate resulted in the
      exclusion of other potentially serious causes of acidosis and in the
      identification of topiramate as the causative agent. In our second patient,
      hyponatremia and status epilepticus resulted from therapy with oxcarbazepine.
      Prompt recognition of hyponatremia, fluid restriction, and cessation of
      oxcarbazepine therapy resulted in prompt correction of the hyponatremia. We
      review previous reports of these adverse effects with topiramate and
      oxcarbazepine, describe the pathophysiology of these metabolic alterations,
      provide treatment strategies, and make suggestions for monitoring patients during
      therapy with these anticonvulsant medications.

PMID- 16634248
TI  - Conversion disorder presenting as hemiplegia and hemianesthesia with loss of
      neurologic reflexes: a case report.
AB  - Conversion disorders can present with a variety of sensorimotor signs and
      symptoms. We present the case of a young woman who presented with sudden onset
      hemiplegia and hemianesthesia including unilateral loss of deep tendon reflexes,
      Babinski reflex, and loss of rectal tone with bladder incontinence. The loss of
      rectal tone, loss of deep tendon reflexes, and a flaccid Babinski reflex are
      unusual signs in conversion disorders. A thorough medical workup including x
      rays, CT scans, and magnetic resonance imaging revealed no organic causes for the
      neurologic deficits. Before the onset of symptoms, the patient was emotionally
      upset during an argument, which may have provided the psychologic stressor
      necessary for a conversion disorder. The young woman gradually regained full
      neurologic function over the next 14 hours. Conversion disorders should be
      considered when the neurologic findings do not correspond to known anatomic or
      physiologic pathways, although a thorough medical investigation must be performed
      to search for organic causes.

PMID- 16634249
TI  - Amiodarone-induced alveolar hemorrhage.
AB  - Amiodarone is increasingly prescribed for patients with ventricular and
      supraventricular tachyarrhythmias. Many adverse effects have been reported due to
      this drug and include injury to the liver, thyroid, cornea, skin, and
      neuromuscular system. Pulmonary toxicity is one of the more serious side effects
      of this anti-arrhythmic drug and is potentially fatal. Since the first case of
      amiodarone-induced pneumonitis was described in the early 1980s, amiodarone
      pneumonitis has been recognized as a distinctive and not uncommon form of drug
      induced lung injury. On the other hand, amiodarone-induced pulmonary toxicity
      resulting in alveolar hemorrhage is rare. The authors report a patient with
      amiodarone-induced alveolar hemorrhage and review the literature.

PMID- 16634250
TI  - Paradoxically developed optochiasmatic tuberculoma and tuberculous lymphadenitis:
      a case report with 18-month follow up by MRI.
AB  - We report the first case ofextracranial tuberculous lymphadenitis which
      paradoxically developed during treatment of intracranial tuberculoma. Our
      patient, a 15-year-old girl who initially presented with meningitis and
      intracranial tuberculomas, developed extracranial tuberculomas during treatment
      for central nervous system tuberculosis. She was followed clinically with
      cerebrospinal fluid (CSF) studies and magnetic resonance imaging (MRI) at three
      monthly intervals. Within 18 months of specific antituberculous treatment, the
      patient had fully recovered. The course and response to therapy are discussed in
      light of the current literature.

PMID- 16634251
TI  - Primary tuberculous liver abscess: a case report and review of the literature.
AB  - A 48-year-old diabetic man was admitted to our hospital with abdominal pain in
      the right upper quadrant, weight loss, night sweats, fatigue, and anorexia.
      Ultrasonography, computed tomography, and magnetic resonance imaging of the
      abdomen revealed multiple hemangiomas and a hypodense mass lesion in the
      posterior segment of the right hepatic lobe. Histopathologic examination of the
      specimens obtained by ultrasonography-guided percutaneous needle biopsy revealed
      caseating granulomas with epithelioid histiocytes and giant cells. Systemic
      antituberculous therapy led to improvement of the lesion in the liver without
      necessitating surgery or percutaneous drainage. Tuberculosis should be considered
      in the differential diagnosis of hepatic mass lesions, especially in the presence
      of immune-compromised states. Ruling out tuberculosis may avoid delay in
      initiation of specific therapy in some cases. A greater awareness of this rare
      clinical entity may prevent needless surgical interventions.

PMID- 16634252
TI  - Treatment of extramammary Paget disease with topical imiquimod cream: case report
      and literature review.
AB  - Extramammary Paget disease is an uncommon cutaneous neoplasm that presents as
      erythematous plaques most frequently located in the anogenital region. Management
      of patients with extramammary Paget disease involves evaluation of the individual
      for: (1) a disease-associated, unsuspected, visceral malignancy and (2) secondary
      adenocarcinoma in the underlying dermis or regional lymph nodes. Several
      modalities, each with variable effectiveness, are available to treat the
      cutaneous component of the disease: electrodesiccation and curettage, laser
      surgery, aminolevulinic acid photodynamic therapy, radiotherapy, topical
      chemotherapy, and wide surgical excision. However, surgical excision using the
      Mohs micrographic technique is currently the modality of choice for treating the
      cutaneous lesions of extramammary Paget disease. Recently, a topical
      imidazoquinoline immunomodulator that induces cytokine production and stimulates
      the innate and cellular immune responses--imiquimod cream-has been used for the
      management of primary or relapsing extramammary Paget disease. Complete healing,
      without recurrence, of extramammary Paget disease in patients whose cutaneous
      lesions were treated topically with imiquimod 5% cream was observed. We describe
      a man with suprapubic extramammary Paget disease whose condition was primary and
      limited to his skin. Biopsy-confirmed complete resolution of his disease was
      observed after the topical application of imiquimod 5% cream 3 times per week (on
      alternate days) for 16 weeks. After reviewing the published reports of other
      patients with extramammary Paget disease whose disease was successfully treated
      with imiquimod cream, we suggest that topical imiquimod 5% cream-at least 3 times
      per week (with 1-2 d of nontreatment in between) for a minimum of 8 to 16 weeks-
      be considered as an initial treatment for primary cutaneous extramammary Paget
      disease. Surgical excision or an alternative therapeutic modality is recommended
      for patients whose extramammary Paget disease persists or recurs after treatment
      with topical imiquimod.

PMID- 16634253
TI  - Newborn screening for cystic fibrosis.

PMID- 16634254
TI  - Systemic infections can decrease the threshold of statin-induced muscle injury.

PMID- 16634255
TI  - Pesticides used in homes and farms in El Paso, Texas.

PMID- 16634256
TI  - Patient's page. How to prevent child abuse.

PMID- 16634257
TI  - Pediatrics during the 20th century.

PMID- 16634258
TI  - Face transplantation: a brave or maverick surgery?

PMID- 16634259
TI  - Saving face.

PMID- 16634260
TI  - Face transplantation: the view from Harvard Medical School.

PMID- 16634261
TI  - Face transplantation: the view from Duke University and the University Of
      Chicago.

PMID- 16634262
TI  - Face transplantation: the view from Vanderbilt University.

PMID- 16634263
TI  - Face transplantation: the view from Paris, France.

PMID- 16634264
TI  - Face transplantation: the view from Birmingham, England.

PMID- 16634265
TI  - Face transplants: is the genie out of the bottle?

PMID- 16634266
TI  - The United States position: Position paper of the American Society for
      Reconstructive Microsurgery on Facial Transplantation.

PMID- 16634267
TI  - The English position: Position paper of the Royal College of Surgeons of England.

PMID- 16634268
TI  - The French position: Comite Consultatif National d'Ethique pour les sciences de
      la vie et de la sante: "Composite tissue allograftransplantation of the face
      (total or partial graft)".

PMID- 16634269
TI  - Case discussion: disease as punishment.

PMID- 16634270
TI  - Educating physicians: are we doing enough?

PMID- 16634271
TI  - Eye on religion: clinicians and Hinduism.

PMID- 16634272
TI  - Selected annotated bibliography.

PMID- 16634273
TI  - Listen to your inner voice.

PMID- 16634274
TI  - Midwives and loss: the cost of caring.

PMID- 16634275
TI  - With woman, with my sister.

PMID- 16634276
TI  - Once more unto the breech.

PMID- 16634277
TI  - Delivering effective communication.

PMID- 16634278
TI  - Midwifery basics: complications (6). Postpartum haemorrhage.

PMID- 16634279
TI  - Research unwrapped. Postnatal breastfeeding support.

PMID- 16634280
TI  - Controlling the capricious cervix (1).

PMID- 16634281
TI  - Think before you speak.

PMID- 16634282
TI  - Effect of eluent pH on the HPLC-UV analysis of hyperforin from St. John's Wort
      (Hypericum perforatum L.).
AB  - The effect of the pH of the mobile phase in HPLC analysis of hyperforin was
      investigated. Working with an extract of St. John's Wort (Hypericum perforatum
      L.) that is rich in hyperforin, significant differences were observed in
      conventional chromatograms depending on whether the mobile phase was acidic or
      alkaline. Chromatogram changes were paralleled by changes in the UV spectrum of
      the hyperforin peak. The structural changes in hyperforin occur in the
      chromatographic column itself, as has been confirmed by UV spectroscopy performed
      on a sample of purified hyperforin, which showed that the UV spectrum is indeed
      dependent on the pH of its environment.

PMID- 16634283
TI  - Identification of isomeric tropane alkaloids from Schizanthus grahamii by HPLC
      NMR with loop storage and HPLC-UV-MS/SPE-NMR using a cryogenic flow probe.
AB  - Two fully automated HPLC-NMR methods are reported and compared for the structure
      elucidation of four isomeric tropane alkaloids from the stem-bark of an endemic
      Chilean plant, Schizanthus grahamii Gill. (Solanaceae). The first approach
      interfaced a conventional HPLC column to NMR by means of a loop storage unit.
      After elution with a mobile phase consisting of deuterated water and standard
      protonated organic solvents, the separated analytes were momentarily stored in a
      loop cassette and then transferred one-at-a-time to the NMR flow probe for
      measurements. The second strategy combined HPLC with parallel ion-trap MS
      detection and NMR spectroscopy using an integrated solid-phase extraction (SPE)
      unit for post-column analyte trapping. The SPE cartridges were dried under a
      gentle stream of nitrogen and analytes were sequentially eluted and directed to a
      cryogenically cooled flow-probe with an NMR-friendly solvent. The structures of
      the four isomeric alkaloids, 3alpha-senecioyloxy-7beta-hydroxytropane, 3alpha
      hydroxy-7beta-angeloyloxytropane, 3alpha-hydroxy-7beta-tigloyloxytropane and
      3alpha-hydroxy-7beta-senecioyloxytropane, were unambiguously determined by
      combining NMR assignments with MS data.

PMID- 16634284
TI  - The structural elucidation of a novel iridoid derivative from Tachiadenus
      longiflorus (Gentianaceae) using the LSD programme and quantum chemical
      computations.
AB  - Oleanolic acid, scoparone, scopoletin and a novel iridoid derivative, angelone,
      were isolated from Tachiadenus longiflorus (Gentianaceae). The structure of
      angelone was determined from NMR data, given as input to the Logic for Structure
      Determination Programme, and was finally confirmed by comparison of experimental
      13C-NMR chemical shifts with those obtained by quantum mechanical calculations.

PMID- 16634285
TI  - Characterisation of volatile organic compounds in stemwood using solid-phase
      microextraction.
AB  - Solid-phase microextraction (SPME), hydrodistillation and dynamic headspace
      combined with GC and GC-MS were applied and compared for the analysis of volatile
      organic compounds (VOCs) from coniferous wood. The SPME conditions (type of
      fibre, size of wood sample, temperature and exposure time) were optimised, and
      more than 100 VOCs and semi-volatile compounds extracted and identified from the
      sapwood and heartwood of Norway spruce (Picea abies). The total number of mono-
      and sesquiterpenes eluted and identified was similar for the SPME and
      hydrodistillation methods, but more semi-volatile compounds were released by
      hydrodistillation. By applying dynamic headspace at room temperature, it was
      possible to analyse only the most volatile compounds. The qualitative composition
      of VOCs was similar in spruce sapwood and heartwood, although Z-beta-ocimene
      occurred only in sapwood while fenchol was present only in heartwood. SPME
      sampling coupled with GC, applied here to the analysis of VOCs released from
      stemwood of firs for the first time, is a convenient, sensitive, fast, solvent
      free and simple method for the determination of wood volatiles. The technique
      requires much smaller sample amounts compared with hydrodistillation, and the
      total amount of VOCs extracted and identified is higher than that obtained by
      hydrodistillation or dynamic headspace. The relative ratios of the main mono- and
      sesquiterpenes and -terpenoids were similar using the SPME-GC and
      hydrodistillation methods.

PMID- 16634286
TI  - Dereplication of pentacyclic triterpenoids in plants by GC-EI/MS.
AB  - Three common plant-derived pentacyclic triterpenoids, oleanolic acid (1),
      betulinic acid (2) and ursolic acid (3), have been found to exhibit moderate anti
      tubercular activity in a microplate alamar blue assay. In order to facilitate the
      discovery of novel anti-tubercular leads with diverse chemical structures, a new
      and rapid GC-EI/MS method was developed simultaneously and unambiguously to
      dereplicate 1-3 as their methyl esters with limits of detection of 25.6, 26.9 and
      26.8 ng, respectively.

PMID- 16634287
TI  - Studies on tropane alkaloid extraction by volatile organic solvents:
      dichloromethane vs. chloroform.
AB  - In order to investigate the production of tropane alkaloids by hairy roots of
      Atropa baetica, transgenic for the gene h6h encoding the enzyme hyoscyamine 6beta
      hydroxylase, solvent extraction with chloroform and with dichloromethane of the
      metabolites present in the liquid medium and in the root tissue was compared. The
      extraction of scopolamine from the liquid medium was equally effective with
      either solvent, giving maximum values of around 850 microg/flask. For the roots,
      three different extraction methods were employed: A, employing
      chloroform:methanol: (25%) ammonia (15:5:1) for initial extraction, followed by
      treatment with sulfuric acid and ammonia, and using chloroform for the final
      extraction and washes; B, as A but using dichloromethane for extraction and
      washes; and C, as B but substituting chloroform for dichloromethane in the
      extraction cocktail. Scopolamine was the most abundant metabolite (present in
      amounts of 3250-3525 microg/g dry weight) and presented similar extraction
      efficiencies with all of the extraction methods employed. The highest amounts of
      hyoscyamine and the intermediate 6beta-hydxoxyhyoscyamine were present on day 31
      (800 and 975 microg/g dry weight, respectively) and no statistical differences
      between the three extraction methods employed were detected. This study confirms
      that, for the extraction of tropane alkaloids, dichloromethane can replace the
      commonly employed chloroform, the use of which incurs major health, security and
      regulation problems.

PMID- 16634288
TI  - Distribution of aflatoxins between extract and extraction residue of paprika
      using supercritical carbon dioxide.
AB  - Paprika powder, naturally contaminated with aflatoxins, was extracted by
      supercritical carbon dioxide at standard conditions (300 bar and 50 degrees C). A
      lipophilic top phase and an aqueous base phase were obtained. These and the
      extraction residue were analysed by HPLC for aflatoxins. The main quantity of
      aflatoxins, about 60% of aflatoxin B1 and about 70% of aflatoxin B2 related to
      the original paprika powder, was found to be located in the extraction residue.
      This confirms the results of previous studies with other spices and demonstrates
      that the use for flavouring purposes of supercritical carbon dioxide extracts,
      rather than natural spice, offers potential application in reducing aflatoxin
      levels in spiced foods.

PMID- 16634289
TI  - Application of near-infrared spectroscopy in quality control and determination of
      adulteration of African essential oils.
AB  - An evaluation has been made of the potential of near-infrared (NIR) technologies
      in the assessment of essential oil components and in the identification of
      individual essential oils. The results showed that cross-validation models are
      able to predict accurately almost all of the components of essential oils. In
      different cinnamon (Cinnamomum zeylanicum) and clove (Syzygium aromaticum)
      essential oils, which showed a similar composition, 23 components (representing
      97.8-99.9% of the oil) were accurately predicted, as well as 20 components (93.0
      99.1%) in Cinnamomum camphora (ravintsara), 32 components (92.3-98.1%) in
      Ravensara aromatica (ravensara), and 26 components (96.6-98.4%) in Lippia
      multiflora. For almost all of the components, the modelled and reference values
      obtained by GC-FID were highly correlated (r2 > or = 0.985) and exhibited a low
      variance (less than 5%). The model was also able to discriminate between the
      ravintsara and ravensara essential oils. It was shown that two commercial oils
      labelled as R. aromatica were actually ravintsara (C. camphora), revealing the
      misidentification of these essential oils in the marketplace. The study
      demonstrates the application of NIR technology as a quality control tool for the
      rapid identification of individual essential oils, for product authentication,
      and for the detection of adulteration.

PMID- 16634290
TI  - A novel method to convert triptolide into tripchlorolide in Tripterygium
      wilfordii.
AB  - A new method has been established to convert triptolide (1) into tripchlorolide
      (2) directly in the Chinese herbal drug Tripterygium wilfordii Hook F. and the
      influences of reaction times and pH values have been investigated. It was found
      that 1 could be most efficiently converted into 2 using a hydrochloric acid
      acetic acid system. An HPLC method was devised in order to monitor the conversion
      and ESI-MS was used to identify the synthetic product 2. The sensitivity of the
      assay was sufficient to monitor the conversion of the main active components in
      T. wilfordii.

PMID- 16634291
TI  - Current awareness in phytochemical analysis.

PMID- 16634292
TI  - Nitrogen uptake, distribution, turnover, and efficiency of use in a CO2-enriched
      sweetgum forest.
AB  - The Progressive Nitrogen Limitation (PNL) hypothesis suggests that ecosystems in
      a CO2-enriched atmosphere will sequester C and N in long-lived biomass and soil
      organic pools, thereby limiting available N and constraining the continued
      response of net primary productivity to elevated [CO2]. Here, we present a six
      year record of N dynamics of a sweetgum (Liquidambar styraciflua) stand exposed
      to elevated [CO2] in the free-air CO2 enrichment (FACE) experiment at Oak Ridge,
      Tennessee, USA. We also evaluate the concept of PNL for this ecosystem from the
      perspective of N uptake, content, distribution, and turnover, and N-use
      efficiency. Leaf N content was 11% lower on a leaf mass basis (NM) and 7% lower
      on a leaf area basis (NA) in CO2-enriched trees. However, there was no effect of
      [CO2] on total canopy N content. Resorption of N during senescence was not
      altered by [CO2], so NM of litter, but not total N content, was reduced. The NM
      of fine roots was not affected, but the total amount of N required for fine-root
      production increased significantly, reflecting the large stimulation of fine-root
      production in this stand. Hence, total N requirement of the trees was higher in
      elevated [CO2], and the increased requirement was met through an increase in N
      uptake rather than increased retranslocation of stored reserves. Increased N
      uptake was correlated with increased net primary productivity (NPP). N-use
      efficiency, however, did not change with CO2 enrichment because increased N
      productivity was offset by lower mean residence time of N in the trees. None of
      the measured responses of plant N dynamics in this ecosystem indicated the
      occurrence of PNL, and the stimulation of NPP by elevated [CO2] was sustained for
      the first six years of the experiment. Although there are some indications of
      developing changes in the N economy, the N supply in the soil at this site may be
      sufficient to meet an increasing demand for available N, especially as the roots
      of CO2-enriched trees explore deeper in the soil profile.

PMID- 16634293
TI  - Progressive nitrogen limitation of ecosystem processes under elevated CO2 in a
      warm-temperate forest.
AB  - A hypothesis for progressive nitrogen limitation (PNL) proposes that net primary
      production (NPP) will decline through time in ecosystems subjected to a step
      function increase in atmospheric CO2. The primary mechanism driving this response
      is a rapid rate of N immobilization by plants and microbes under elevated CO2
      that depletes soils of N, causing slower rates of N mineralization. Under this
      hypothesis, there is little long-term stimulation of NPP by elevated CO2 in the
      absence of exogenous inputs of N. We tested this hypothesis using data on the
      pools and fluxes of C and N in tree biomass, microbes, and soils from 1997
      through 2002 collected at the Duke Forest free-air CO2 enrichment (FACE)
      experiment. Elevated CO2 stimulated NPP by 18-24% during the first six years of
      this experiment. Consistent with the hypothesis for PNL, significantly more N was
      immobilized in tree biomass and in the O horizon under elevated CO2. In contrast
      to the PNL hypothesis, microbial-N immobilization did not increase under elevated
      CO2, and although the rate of net N mineralization declined through time, the
      decline was not significantly more rapid under elevated CO2. Ecosystem C-to-N
      ratios widened more rapidly under elevated CO2 than ambient CO2 indicating a more
      rapid rate of C fixation per unit of N, a processes that could delay PNL in this
      ecosystem. Mass balance calculations demonstrated a large accrual of ecosystem N
      capital. Is PNL occurring in this ecosystem and will NPP decline to levels under
      ambient CO2? The answer depends on the relative strength of tree biomass and O
      horizon N immobilization vs. widening C-to-N ratios and ecosystem-N accrual as
      processes that drive and delay PNL, respectively. Only direct observations
      through time will definitively answer this question.

PMID- 16634294
TI  - Nitrogen cycling during seven years of atmospheric CO2 enrichment in a scrub oak
      woodland.
AB  - Experimentally increasing atmospheric CO2 often stimulates plant growth and
      ecosystem carbon (C) uptake. Biogeochemical theory predicts that these initial
      responses will immobilize nitrogen (N) in plant biomass and soil organic matter,
      causing N availability to plants to decline, and reducing the long-term CO2
      stimulation of C storage in N limited ecosystems. While many experiments have
      examined changes in N cycling in response to elevated CO2, empirical tests of
      this theoretical prediction are scarce. During seven years of postfire recovery
      in a scrub oak ecosystem, elevated CO2 initially increased plant N accumulation
      and plant uptake of tracer 15N, peaking after four years of CO2 enrichment.
      Between years four and seven, these responses to CO2 declined. Elevated CO2 also
      increased N and tracer 15N accumulation in the O horizon, and reduced 15N
      recovery in underlying mineral soil. These responses are consistent with
      progressive N limitation: the initial CO2 stimulation of plant growth immobilized
      N in plant biomass and in the O horizon, progressively reducing N availability to
      plants. Litterfall production (one measure of aboveground primary productivity)
      increased initially in response to elevated CO2, but the CO2 stimulation declined
      during years five through seven, concurrent with the accumulation of N in the O
      horizon and the apparent restriction of plant N availability. Yet, at the level
      of aboveground plant biomass (estimated by allometry), progressive N limitation
      was less apparent, initially because of increased N acquisition from soil and
      later because of reduced N concentration in biomass as N availability declined.
      Over this seven-year period, elevated CO2 caused a redistribution of N within the
      ecosystem, from mineral soils, to plants, to surface organic matter. In N limited
      ecosystems, such changes in N cycling are likely to reduce the response of plant
      production to elevated CO2.

PMID- 16634295
TI  - Potential nitrogen constraints on soil carbon sequestration under low and
      elevated atmospheric CO2.
AB  - The interaction between nitrogen cycling and carbon sequestration is critical in
      predicting the consequences of anthropogenic increases in atmospheric CO2
      (hereafter, Ca). The progressive N limitation (PNL) theory predicts that carbon
      sequestration in plants and soils with rising Ca may be constrained by the
      availability of nitrogen in many ecosystems. Here we report on the interaction
      between C and N dynamics during a four-year field experiment in which an intact
      C3/C4 grassland was exposed to a gradient in Ca from 200 to 560 micromol/mol.
      There were strong species effects on decomposition dynamics, with C loss
      positively correlated and N mineralization negatively correlated with Ca for
      litter of the C3 forb Solanum dimidiatum, whereas decomposition of litter from
      the C4 grass Bothriochloa ischaemum was unresponsive to Ca. Both soil microbial
      biomass and soil respiration rates exhibited a nonlinear response to Ca, reaching
      a maximum at approximately 440 micromol/mol Ca. We found a general movement of N
      out of soil organic matter and into aboveground plant biomass with increased Ca.
      Within soils we found evidence of C loss from recalcitrant soil C fractions with
      narrow C:N ratios to more labile soil fractions with broader C:N ratios,
      potentially due to decreases in N availability. The observed reallocation of N
      from soil to plants over the last three years of the experiment supports the PNL
      theory that reductions in N availability with rising Ca could initially be
      overcome by a transfer of N from low C:N ratio fractions to those with higher C:N
      ratios. Although the transfer of N allowed plant production to increase with
      increasing Ca, there was no net soil C sequestration at elevated Ca, presumably
      because relatively stable C is being decomposed to meet microbial and plant N
      requirements. Ultimately, if the C gained by increased plant production is
      rapidly lost through decomposition, the shift in N from older soil organic matter
      to rapidly decomposing plant tissue may limit net C sequestration with increased
      plant production.

PMID- 16634296
TI  - Elevated CO2 stimulates net accumulations of carbon and nitrogen in land
      ecosystems: a meta-analysis.
AB  - The capability of terrestrial ecosystems to sequester carbon (C) plays a critical
      role in regulating future climatic change yet depends on nitrogen (N)
      availability. To predict long-term ecosystem C storage, it is essential to
      examine whether soil N becomes progressively limiting as C and N are sequestered
      in long-lived plant biomass and soil organic matter. A critical parameter to
      indicate the long-term progressive N limitation (PNL) is net change in ecosystem
      N content in association with C accumulation in plant and soil pools under
      elevated CO2. We compiled data from 104 published papers that study C and N
      dynamics at ambient and elevated CO2. The compiled database contains C contents,
      N contents, and C:N ratio in various plant and soil pools, and root:shoot ratio.
      Averaged C and N pool sizes in plant and soil all significantly increase at
      elevated CO2 in comparison to those at ambient CO2, ranging from a 5% increase in
      shoot N content to a 32% increase in root C content. The C and N contents in
      litter pools are consistently higher in elevated than ambient CO2 among all the
      surveyed studies whereas C and N contents in the other pools increase in some
      studies and decrease in other studies. The high variability in CO2-induced
      changes in C and N pool sizes results from diverse responses of various C and N
      processes to elevated CO2. Averaged C:N ratios are higher by 3% in litter and
      soil pools and 11% in root and shoot pools at elevated relative to ambient CO2.
      Elevated CO2 slightly increases root:shoot ratio. The net N accumulation in plant
      and soil pools at least helps prevent complete down-regulation of, and likely
      supports, long-term CO2 stimulation of C sequestration. The concomitant C and N
      accumulations in response to rising atmospheric CO2 may reflect intrinsic nature
      of ecosystem development as revealed before by studies of succession over
      hundreds to millions of years.

PMID- 16634297
TI  - Progressive N limitation in forests: review and implications for long-term
      responses to elevated CO2.
AB  - Field studies have shown that elevated CO2 can cause increased forest growth over
      the short term (<6 years) even in the face of N limitation. This is facilitated
      to some degree by greater biomass production per unit N uptake (lower tissue N
      concentrations), but more often than not, N uptake is increased with elevated CO2
      as well. Some studies also show that N sequestration in the forest floor is
      increased with elevated CO2. These findings raise the questions of where the
      "extra" N comes from and how long such growth increases can continue without
      being truncated by progressive N limitation (PNL). This paper reviews some of the
      early nutrient cycling literature that describes PNL during forest stand
      development and attempts to use this information, along with recent developments
      in soil N research, to put the issue of PNL with elevated CO2 into perspective.
      Some of the early studies indicated that trees can effectively "mine" N from
      soils over the long term, and more recent developments in soil N cycling research
      suggest mechanisms by which this might have occurred. However, both the early
      nutrient cycling literature and more recent simulation modeling suggest that PNL
      will at some point truncate the observed increases in growth and nutrient uptake
      with elevated CO2, unless external inputs of N are increased by either N fixation
      or atmospheric deposition.

PMID- 16634298
TI  - Temperature influences carbon accumulation in moist tropical forests.
AB  - Evergreen broad-leaved tropical forests can have high rates of productivity and
      large accumulations of carbon in plant biomass and soils. They can therefore play
      an important role in the global carbon cycle, influencing atmospheric CO2
      concentrations if climate warms. We applied meta-analyses to published data to
      evaluate the apparent effects of temperature on carbon fluxes and storages in
      mature, moist tropical evergreen forest ecosystems. Among forests, litter
      production, tree growth, and belowground carbon allocation all increased
      significantly with site mean annual temperature (MAT); total net primary
      productivity (NPP) increased by an estimated 0.2-0.7 Mg C x ha(-1) x yr(-1) x
      degrees C(-1). Temperature had no discernible effect on the turnover rate of
      aboveground forest biomass, which averaged 0.014 yr(-1) among sites. Consistent
      with these findings, forest biomass increased with site MAT at a rate of 5-13 Mg
      C x ha(-1) x degrees C(-1). Despite greater productivity in warmer forests, soil
      organic matter accumulations decreased with site MAT, with a slope of -8 Mg C x
      ha(-1) x degrees C(-1), indicating that decomposition rates of soil organic
      matter increased with MAT faster than did rates of NPP. Turnover rates of surface
      litter also increased with temperature among forests. We found no detectable
      effect of temperature on total carbon storage among moist-tropical evergreen
      forests, but rather a shift in ecosystem structure, from low-biomass forests with
      relatively large accumulations of detritus in cooler sites, to large-biomass
      forests with relatively smaller detrital stocks in warmer locations. These
      results imply that, in a warmer climate, conservation of forest biomass will be
      critical to the maintenance of carbon stocks in moist tropical forests.

PMID- 16634299
TI  - Male turnover reduces population growth: an enclosure experiment on voles.
AB  - Turnover of individuals is assumed to cause disruptions of social organization,
      followed by reduced reproduction and survival. We tested how male turnover
      (removal of resident males and their replacement by unfamiliar males) affected
      population performance in experimental root vole (Microtus oeconomus)
      populations. The treatment simulated predation of adult males, with the
      subsequent replacement by immigrants, and provided insight into the interaction
      between extrinsic (i.e., predation) and intrinsic (i.e., social organization)
      factors. We showed that recruitment and female survival dramatically declined and
      that reproduction commenced slightly later in treatment populations compared with
      control populations. The treatment nearly halved the population growth rate. We
      suspect that recruitment failed due to infanticidal immigrating males. Reduced
      female survival was particularly apparent in treatment populations in which
      females exhibited a high degree of spatial overlap. Our experimental results show
      how males may significantly shape population dynamics and suggest how predation
      and social factors interact mechanistically.

PMID- 16634300
TI  - Spatial and temporal variability modify density dependence in populations of
      large herbivores.
AB  - A central challenge in ecology is to understand the interplay of internal and
      external controls on the growth of populations. We examined the effects of
      temporal variation in weather and spatial variation in vegetation on the strength
      of density dependence in populations of large herbivores. We fit three subsets of
      the model ln(Nt) = a + (1 + b) x ln(N(t-1)) + c x ln(N(t-2)) to five time series
      of estimates (Nt) of abundance of ungulates in the Rocky Mountains, USA. The
      strength of density dependence was estimated by the magnitude of the coefficient
      b. We regressed the estimates of b on indices of temporal heterogeneity in
      weather and spatial heterogeneity in resources. The 95% posterior intervals of
      the slopes of these regressions showed that temporal heterogeneity strengthened
      density-dependent feedbacks to population growth, whereas spatial heterogeneity
      weakened them. This finding offers the first empirical evidence that density
      dependence responds in different ways to spatial heterogeneity and temporal
      heterogeneity.

PMID- 16634301
TI  - Temporal dynamics of antagonism and mutualism in a geographically variable plant
      insect interaction.
AB  - Variation among sites and years in the local ecological outcome of interspecific
      interactions can generate a geographic mosaic of coevolution, as indicated by
      recent mathematical models. We evaluated whether local temporal dynamics of
      ecological outcome in the interaction between the moth Greya politella
      (Prodoxidae) and its host plant Lithophragma parviflorum (Saxifragaceae) are
      likely to mitigate or magnify geographic differences in ecological outcome found
      in earlier studies. The moths are highly host-specific pollinating floral
      parasites, and the mutualism can be swamped in some populations by the presence
      of effective co-pollinators. Hence, differing community contexts can shift the
      outcome of the interaction from mutualism to commensalism or antagonism. During
      each of four years, we evaluated the effect of Greya oviposition on seed
      development through a paired design that controlled for plant genotype and
      microenvironment. At Turnbull National Wildlife Refuge in Washington State, the
      interaction was significantly mutualistic in all four years. Mutualism in this
      population was indicated by a higher probability of development of capsules
      visited by ovipositing Greya than capsules not visited by Greya on the same
      plant. At Rapid River, Idaho, the interaction was commensalistic in three years
      and antagonistic in one year. Antagonism in this population was indicated by
      selective withering of capsules containing Greya eggs. Overall, the results
      suggest stable geographic differences in the range of ecological outcomes in this
      plant-insect interaction under different community contexts.

PMID- 16634302
TI  - Habitat-specific impacts of multiple consumers on plant population dynamics.
AB  - Multiple consumers often attack seeds, seedlings, and adult plants, but their
      population-level consequences remain uncertain. We examined how insect and small
      mammal consumers influenced the demography and abundance of the perennial shrub,
      bush lupine (Lupinus arboreus). In grassland and dune habitats we established
      replicate experimental lupine populations in 81-m2 plots that were either
      protected from, or exposed to, herbivorous voles and granivorous mice (via
      fencing) and/or root feeding insects (via insecticide treatment). Populations
      were initiated with transplanted seedlings in 1999 and 2000. We followed the
      demography of these cohorts, subsequent generations, and the seed bank for 5.5
      years. Voles and insects killed many seedlings in dune (1999 only) and grassland
      (1999 and 2000) habitats. After 2000, insects and voles had minimal effects on
      seedling or adult survival. Seed predation by granivorous mice, however, greatly
      depressed seedling recruitment, resulting in lower adult lupine abundance in
      control plots vs. those protected from rodents. In grasslands, initial effects of
      voles and insects on seedling survival produced large differences among
      treatments in adult plant density and the cumulative number of seeds produced
      throughout the experiment. Differences among grassland populations in seed rain,
      however, had little influence on the magnitude of seedling recruitment into this
      habitat. Instead, recruitment out of a preexisting seed bank compensated for the
      lack of seed production in populations exposed to consumers. Shading by dense
      adults in plots protected from consumers limited seedling establishment within
      these populations. Although differences among populations in cumulative seed rain
      did not influence adult establishment, populations protected from consumers
      accumulated substantially larger seed banks than controls. These results
      illustrate how density dependence, habitat-specific seed dynamics, and particular
      demographic impacts of consumers interact to shape plant population responses to
      consumers.

PMID- 16634303
TI  - Nonrandom movement behavior at habitat boundaries in two butterfly species:
      implications for dispersal.
AB  - We observed meadow brown (Maniola jurtina) and gatekeeper (Pyronia tithonus)
      butterflies at habitat boundaries and observed spontaneous movements out of
      suitable habitat in order to investigate such movements in relation to dispersal.
      We found that butterflies of both species were aware of the position of a highly
      permeable habitat boundary without needing to cross it. Nevertheless, a
      considerable proportion of butterflies close to the boundary left their habitat
      (25-43%). Butterflies that crossed the boundary, and moved substantial distances
      into unsuitable habitat (up to 350 m in M. jurtina and 70 m in P. tithonus),
      usually returned to their original habitat patch (98-100%). Movement
      trajectories, at least in M. jurtina, were significantly different from, and more
      directed and systematic than, a correlated random walk. Approximately 70-80% of
      spontaneous movements into unsuitable habitat in both species were "foray" loops
      comparable to those described in mammals and birds. We conclude that, since
      migrants seemed to have considerable control over leaving their patch and over
      their subsequent movement trajectories, chance encounter rates with habitat
      boundaries, and indeed habitat leaving rates, might be less crucial in
      determining dispersal rates than is usually assumed. In addition, random
      dispersal trajectories should not be taken for granted in population or evolution
      models.

PMID- 16634304
TI  - Why do most tropical animals reproduce seasonally? Testing hypotheses on an
      Australian snake.
AB  - Most species reproduce seasonally, even in the tropics where activity occurs year
      round. Squamate reptiles provide ideal model organisms to clarify the ultimate
      (adaptive) reasons for the restriction of reproduction to specific times of year.
      Females of almost all temperate-zone reptile species produce their eggs or
      offspring in the warmest time of the year, thereby synchronizing embryogenesis
      with high ambient temperatures. However, although tropical reptiles are freed
      from this thermal constraint, most do not reproduce year-round. Seasonal
      reproduction in tropical reptiles might be driven by biotic factors (e.g., peak
      periods of predation on eggs or hatchlings, or food for hatchlings) or abiotic
      factors (e.g., seasonal availability of suitably moist incubation conditions).
      Keelback snakes (Tropidonophis mairii, Colubridae) in tropical Australia
      reproduce from April to November, but with a major peak in May-June. Our field
      studies falsify hypotheses that invoke biotic factors as explanations for this
      pattern: the timing of nesting does not minimize predation on eggs, nor maximize
      food availability or survival rates for hatchlings. Instead, our data implicate
      abiotic factors: female keelbacks nest most intensely soon after the cessation of
      monsoonal rains when soils are moist enough to sustain optimal embryogenesis
      (wetter nests produce larger hatchlings, that are more likely to survive) but are
      unlikely to become waterlogged (which is lethal to eggs). Thus, abiotic factors
      may favor seasonal reproduction in tropical as well as temperate-zone animals.

PMID- 16634305
TI  - Habitat fragmentation and effects of herbivore (howler monkey) abundances on bird
      species richness.
AB  - Habitat fragmentation can alter herbivore abundances, potentially causing changes
      in the plant community that can propagate through the food web and eventually
      influence other important taxonomic groups such as birds. Here we test the
      relationship between the density of red howler monkeys (Alouatta seniculus) and
      bird species richness on a large set of recently isolated land-bridge islands in
      Lago Guri, Venezuela (n = 29 islands). Several of these islands host relict
      populations of howler monkeys at densities up to more than 30 times greater than
      those on the mainland. These "hyperabundant" herbivores previously have been
      shown to have a strong positive influence on aboveground plant productivity. We
      predicted that this should lead to a positive, indirect effect of howler monkey
      density on bird species richness. After accounting for passive sampling (the
      tendency for species richness to be positively associated with island area,
      regardless of differences in habitat quality) we found a significant positive
      correlation between howler monkey density and bird species richness. A path
      analysis incorporating data on tree growth rates from a subset of islands (n = 9)
      supported the hypothesis that the effect of howler monkeys on the resident bird
      communities is indirect and is mediated through changes in plant productivity and
      habitat quality. These results highlight the potential for disparate taxonomic
      groups to be related through indirect interactions and trophic cascades.

PMID- 16634306
TI  - Effects of El Nino on distribution and reproductive performance of Black Brant.
AB  - Climate in low-latitude wintering areas may influence temperate and high-latitude
      breeding populations of birds, but demonstrations of such relationships have been
      rare because of difficulties in linking wintering with breeding populations. We
      used long-term aerial surveys in Mexican wintering areas and breeding areas in
      Alaska, USA, to assess numbers of Black Brant (Branta bernicla nigricans;
      hereafter brant) on their principal wintering and breeding area in El Nino and
      non-El Nino years. We used Pollock's robust design to directly estimate
      probability of breeding and apparent annual survival of individually marked brant
      at the Tutakoke River (TR) colony, Alaska, in each year between 1988 and 2001.
      Fewer brant wintered in Mexico during every El Nino event since 1965. Fewer brant
      were observed on the principal breeding area following each El Nino since surveys
      began in 1985. Probability of breeding was negatively related to January sea
      surface temperature along the subtropical coast of North America during the
      preceding winter. Between 23% (five-year-olds or older) and 30% (three-year-olds)
      fewer brant nested in 1998 following the strong El Nino event in the winter of
      1997-1998 than in non-El Nino years. This finding is consistent with life history
      theory, which predicts that longer-lived species preserve adult survival at the
      expense of reproduction. Oceanographic conditions off Baja California, apparently
      by their effect on Zostera marina (eelgrass), strongly influence winter
      distribution of brant geese and their reproduction (but not survival), which in
      turn affects ecosystem dynamics in Alaska.

PMID- 16634307
TI  - Independent effects of food and predator-mediated processes on annual fecundity
      in a songbird.
AB  - We investigated the relative importance and interaction of ecological processes
      affecting annual fecundity in birds by simultaneously manipulating food
      availability and nest predation risk in a small songbird, the Wrentit (Chamaea
      fasciata). From 2000 to 2002 we provided supplemental food to individual Wrentit
      territories, and during 2002 we altered nest predation risk by providing
      supplemental food to their principal predators, Western Scrub-Jays (Aphelocoma
      californica). These experiments were conducted during a period of high
      interannual variation in rainfall, with 2002 being one of the driest years on
      record. Food-supplemented Wrentits in a normal predation environment produced an
      average of 0.54 more fledglings per year than control pairs over the three
      breeding seasons. During the feeding plus predation manipulation experiment,
      Wrentit food supplementation and lowered nest predation risk each independently
      increased the probability that a Wrentit pair would fledge young; however, the
      interaction between food supplementation and altered nest predation risk was not
      significant. Thus, even in an extreme drought year, both food and nest predation
      had equal but independent effects on reproductive success and annual fecundity.
      Combining supplemental food with reduced nest predation did not result in a
      synergistic increase in annual fecundity, primarily because Wrentits did not
      produce multiple broods. Our results suggest that whether food and predation have
      additive or synergistic effects on reproductive success depends on the life
      history of the species and the environment in which they live.

PMID- 16634308
TI  - Combining multistate capture-recapture data with tag recoveries to estimate
      demographic parameters.
AB  - Matrix population models that allow an animal to occupy more than one state over
      time are important tools for population and evolutionary ecologists. Definition
      of state can vary, including location for metapopulation models and breeding
      state for life history models. For populations whose members can be marked and
      subsequently reencountered, multistate mark-recapture models are available to
      estimate the survival and transition probabilities needed to construct population
      models. Multistate models have proved extremely useful in this context, but they
      often require a substantial amount of data and restrict estimation of transition
      probabilities to those areas or states subjected to formal sampling effort. At
      the same time, for many species, there are considerable tag recovery data
      provided by the public that could be modeled in order to increase precision and
      to extend inference to a greater number of areas or states. Here we present a
      statistical model for combining multistate capture-recapture data (e.g., from a
      breeding ground study) with multistate tag recovery data (e.g., from wintering
      grounds). We use this method to analyze data from a study of Canada Geese (Branta
      canadensis) in the Atlantic Flyway of North America. Our analysis produced
      marginal improvement in precision, due to relatively few recoveries, but we
      demonstrate how precision could be further improved with increases in the
      probability that a retrieved tag is reported.

PMID- 16634309
TI  - Modeling post-fledging survival of Lark Buntings in response to ecological and
      biological factors.
AB  - We evaluated the influences of several ecological, biological, and methodological
      factors on post-fledging survival of a shortgrass prairie bird, the Lark Bunting
      (Calamospiza melanocorys). We estimated daily post-fledging survival (n = 206, 82
      broods) using radiotelemetry and color bands to track fledglings. Daily survival
      probabilities were best explained by drought intensity, time in season (quadratic
      trend), ages < or = 3 d post-fledging, and rank given drought intensity. Drought
      intensity had a strong negative effect on survival. Rank was an important
      predictor of fledgling survival only during the severe drought of 2002 when the
      smallest fledglings had lower survival. Recently fledged young (ages < or = 3 d
      post-fledging) undergoing the transition from nest to surrounding habitat
      experienced markedly lower survival, demonstrating the vulnerable nature of this
      time period. Survival was greater in mid and late season than early season,
      corresponding to our assumptions of food availability. Neither mark type nor sex
      of attending parent influenced survival. The model-averaged product of the 22-d
      survival calculated using mean rank and median value of time in season was 0.360
      +/- 0.08 in 2001 and 0.276 +/- 0.08 in 2002. Survival estimates that account for
      age, condition of young, ecological conditions, and other factors are important
      for parameterization of realistic population models. Biologists using population
      growth models to elucidate mechanisms of population declines should attempt to
      estimate species-specific of post-fledging survival rather than use generalized
      estimates.

PMID- 16634310
TI  - Sampling variability and estimates of density dependence: a composite-likelihood
      approach.
AB  - It is well known that sampling variability, if not properly taken into account,
      affects various ecologically important analyses. Statistical inference for
      stochastic population dynamics models is difficult when, in addition to the
      process error, there is also sampling error. The standard maximum-likelihood
      approach suffers from large computational burden. In this paper, I discuss an
      application of the composite-likelihood method for estimation of the parameters
      of the Gompertz model in the presence of sampling variability. The main advantage
      of the method of composite likelihood is that it reduces the computational burden
      substantially with little loss of statistical efficiency. Missing observations
      are a common problem with many ecological time series. The method of composite
      likelihood can accommodate missing observations in a straightforward fashion.
      Environmental conditions also affect the parameters of stochastic population
      dynamics models. This method is shown to handle such nonstationary population
      dynamics processes as well. Many ecological time series are short, and
      statistical inferences based on such short time series tend to be less precise.
      However, spatial replications of short time series provide an opportunity to
      increase the effective sample size. Application of likelihood-based methods for
      spatial time-series data for population dynamics models is computationally
      prohibitive. The method of composite likelihood is shown to have significantly
      less computational burden, making it possible to analyze large spatial time
      series data. After discussing the methodology in general terms, I illustrate its
      use by analyzing a time series of counts of American Redstart (Setophaga
      ruticilla) from the Breeding Bird Survey data, San Joaquin kit fox (Vulpes
      macrotis mutica) population abundance data, and spatial time series of Bull trout
      (Salvelinus confluentus) redds count data.

PMID- 16634311
TI  - Constrained additive ordination.
AB  - For several decades now, ecologists have sought to determine the shape of
      species' response curves and how they are distributed along unknown underlying
      gradients, environmental latent variables, or ordination axes. Its determination
      has important implications for both continuum theory and community analysis
      because many theories and models in community ecology assume that responses are
      symmetric and unimodal. This article proposes a major new technique called
      constrained additive ordination (CAO) that solves this problem by computing the
      optimal gradients and flexible response curves. It allows ecologists to see the
      response curves as they really are, against the dominant gradients. With one
      gradient, CAO is a generalization of constrained quadratic ordination (CQO;
      formerly called canonical Gaussian ordination or CGO). It supplants symmetric
      bell-shaped response curves in CQO with completely flexible smooth curves. The
      curves are estimated using smoothers such as the smoothing spline. Loosely
      speaking, CAO models are generalized additive models (GAMs) fitted to a very
      small number of latent variables. Being data driven rather than model driven, CAO
      allows the data to "speak for itself" and does not make any of the assumptions
      made by canonical correspondence analysis. The new methodology is illustrated
      with a hunting spider data set and a New Zealand tree species data set.

PMID- 16634312
TI  - Offspring size effects mediate competitive interactions in a colonial marine
      invertebrate.
AB  - Over the past 30 years, numerous attempts to understand the relationship between
      offspring size and fitness have been made, and it has become clear that this
      critical relationship is strongly affected by environmental heterogeneity. For
      marine invertebrates, there has been a long-standing interest in the evolution of
      offspring size, but there have been very few empirical and theoretical
      examinations of post-metamorphic offspring size effects, and almost none have
      considered the effect of environmental heterogeneity on the offspring
      size/fitness relationship. We investigated the post-metamorphic effects of
      offspring size in the field for the colonial marine invertebrate Botrylloides
      violaceus. We also examined how the relationship between offspring size and
      performance was affected by three different types of intraspecific competition.
      We found strong and persistent effects of offspring size on survival and growth,
      but these effects depended on the level and type of intraspecific competition.
      Generally, competition strengthened the advantages of increasing maternal
      investment. Interestingly, we found that offspring size determined the outcome of
      competitive interaction: juveniles that had more maternal investment were more
      likely to encroach on another juvenile's territory. This suggests that mothers
      have the previously unrecognized potential to influence the outcome of
      competitive interactions in benthic marine invertebrates. We created a simple
      optimality model, which utilized the data generated from our field experiments,
      and found that increasing intraspecific competition resulted in an increase in
      predicted optimal size. Our results suggest that the relationship between
      offspring size and fitness is highly variable in the marine environment and
      strongly dependent on the density of conspecifics.

PMID- 16634313
TI  - Conditional outcomes of facilitation by a habitat-modifying subtidal bivalve.
AB  - Facilitation by habitat modifiers is common in ecological communities, but the
      potential for temporal and spatial variations in environmental conditions to
      modify the outcome of these interactions and influence the strength of feedbacks
      is poorly understood. Suspension-feeding bivalves are important habitat modifiers
      that can facilitate surrounding communities by providing refuge from predation
      and changing boundary flows and through the production of organically enriched
      biodeposits. However, numerous studies have highlighted the problem of finding
      generalizable patterns. We tested the strength and generality of the relationship
      between the large suspension-feeding bivalve Atrina zelandica and surrounding
      macrofauna and hypothesized that facilitation by Atrina is conditional and
      modulated by site-specific suspended sediment concentration (SSC), which
      influences the quantity and quality of biodeposit production. We found temporally
      consistent patterns of higher rates of biodeposition and increased abundance and
      species richness in close proximity to Atrina under low SSC conditions.
      Facilitation strength decreased with increasing SSC, suggesting that the
      facilitation effect of Atrina is reduced and reversed along this environmental
      stress gradient.

PMID- 16634314
TI  - Incorporation of plant carbon into the soil animal food web of an arable system.
AB  - We used stable isotopes to examine the incorporation of plant carbon into the
      belowground food web of an agricultural system. Plots were established and
      planted with maize (Zea mays) in a rye field (Secale cereale) near Gottingen
      (northern Germany) in May 1999. In October 1999, April 2000, and October 2000,
      meso- and macrofauna and maize and rye litter were collected in each plot and
      analyzed for 13C and 15N content. 15N signatures suggested that the soil animal
      species analyzed span three trophic levels with the trophic position of species
      varying little in time. The species investigated formed a continuum from primary
      to secondary decomposers to predators. On average, predator species differed from
      primary and secondary decomposers by 3.9 sigma15N suggesting that they fed on a
      mixed diet of both decomposer groups. The combined analysis of 13C and 15N
      signatures allowed us to identify links between prey and consumer species. In
      October 1999, shortly after maize residues had been incorporated into the plots,
      maize-born carbon was present in each of the animal species investigated,
      including top predators. The incorporation of maize carbon into the belowground
      food web increased during the following 12 months but the concentration of maize
      born carbon never exceeded 50% in any of the species. Furthermore, the ranks of
      the incorporation of maize-born carbon of the species changed little. The results
      suggest that the belowground food web relies heavily on carbon originating from
      plant residues from before the recent two growing seasons. In most species the
      amount of maize-born carbon increased continuously; however, in some species it
      decreased during winter, suggesting that these species switched to a diet based
      more on C3 plants during winter, or predominantly metabolized carbon incorporated
      during the last growing season. The study documents that the combined analysis of
      13C and 15N signatures in soil invertebrate species, after replacement of C3 by
      C4 plants, is a powerful tool to better understand the structure of the
      belowground food web and the flux of carbon through it.

PMID- 16634315
TI  - Biotic habitat complexity controls species diversity and nutrient effects on net
      biomass production.
AB  - Canopy-forming plants and algae commonly contribute to spatial variation in
      habitat complexity for associated organisms and thereby create a biotic
      patchiness of communities. In this study, we tested for interaction effects
      between biotic habitat complexity and resource availability on net biomass
      production and species diversity of understory macroalgae by factorial field
      manipulations of light, nutrients, and algal canopy cover in a subtidal rocky
      shore community. Presence of algal canopy cover and/or artificial shadings
      limited net biomass production and facilitated species diversity. Artificial
      shadings reduced light to levels similar to those under canopy cover, and net
      biomass production was significantly and positively correlated to light
      availability. Considering the comparable and dependent experimental effects from
      shadings and canopy cover, the results strongly suggest that canopy cover
      controlled net biomass production and species diversity by limiting light and
      thereby limiting resource availability for community production. Canopy cover
      also controlled experimental nutrient effects by preventing a significant
      increase in net biomass production from nutrient enrichment recorded in ambient
      light (no shading). Changes in species diversity were mediated by changes in
      species dominance patterns and species evenness, where canopy cover and shadings
      facilitated slow-growing crust-forming species and suppressed spatial dominance
      by Fucus vesiculosus, which was the main contributor to net production of algal
      biomass. The demonstrated impacts of biotic habitat complexity on biomass
      production and local diversity contribute significantly to understanding the
      importance of functionally important species and biodiversity for ecosystem
      processes. In particular, this study demonstrates how loss of a dominant species
      and decreased habitat complexity change the response of the remaining assembly to
      resource loading. This is of potential significance for marine conservation since
      resource loading often promotes low habitat complexity and canopy species are
      among the first groups lost in degraded aquatic systems.

PMID- 16634316
TI  - Plant genes link forests and streams.
AB  - Although it is understood that the composition of riparian trees can affect
      stream function through leaf litter fall, the potential effects of genetic
      variation within species are less understood. Using a naturally hybridizing
      cottonwood system, we examined the hypothesis that genetic differences among two
      parental species (Populus fremontii and P. angustifolia) and two groups of their
      hybrids (F1 and backcrosses to P. angustifolia) would affect litter decomposition
      rates and the composition of the aquatic invertebrate community that colonizes
      leaves. Three major findings emerged: (1) parental and hybrid types differ in
      litter quality, (2) decomposition differs between two groups, a fast group (P.
      fremontii and F1 hybrid), and a slow group (P. angustifolia and backcross
      hybrids), and (3) aquatic invertebrate communities colonizing P. fremontii litter
      differed significantly in composition from all other cross types, even though P.
      fremontii and the F1 hybrid decomposed at similar rates. These findings are in
      agreement with terrestrial arthropod studies in the same cottonwood system.
      However, the effects are less pronounced aquatically than those observed in the
      adjacent terrestrial community, which supports a genetic diffusion hypothesis.
      Importantly, these findings argue that genetic interactions link terrestrial and
      aquatic communities and may have significant evolutionary and conservation
      implications.

PMID- 16634321
TI  - Someone to talk to.

PMID- 16634322
TI  - So you have been called to court....

PMID- 16634323
TI  - What's the alternative?

PMID- 16634324
TI  - Practice makes perfect. The removal of body piercings.

PMID- 16634325
TI  - Triage and transport decisions after mass casualty incidents.

PMID- 16634326
TI  - Identifying De Quervain's tenosynovitis.

PMID- 16634327
TI  - Pericardial conditions: signs, symptoms and electrocardiogram changes.
AB  - This article describes the anatomy and physiology of the pericardium and the
      signs and symptoms of acute pericarditis, pericardial effusion and cardiac
      tamponade. It illustrates the likely electrocardiogram findings in each of these
      conditions and discusses how the results, combined with patient history and
      physical examination, can help emergency nurses make accurate diagnoses.

PMID- 16634328
TI  - Acute amitriptyline intoxication: an analysis of 44 children.
AB  - The tricyclic antidepressant agents, particularly amitriptyline and dothiepin,
      are recognized for their potentially lethal cardiovascular and neurological
      effects in poisoned patients. In this article, the clinical and laboratory
      findings of 44 children with amitriptyline intoxication are reviewed. Our purpose
      was to investigate amitriptyline intoxication in childhood. Of 44 patients, 21
      (47.7%) were boys, 23 (52.3%) were girls, and the ages ranged from 12 months to
      14 years (mean +/- SD; 4.09 +/- 2.9 years). All children except one who took an
      overdose of amitriptyline to decrease his pain accidentally ingested an overdose
      of amitriptyline. The amount of amitriptyline ingested was between 2 mg/kg and
      97.5 mg/kg (mean +/- SD; 13.6 +/- 17.7 mg/kg per dose) (the drug dosage was not
      known in 13 children). The most commonly observed clinical and laboratory
      findings were lethargy, tachycardia, convulsion, hyperglycemia and leukocytosis.
      In all patients except for two children who died the abnormal clinical and
      laboratory findings returned to normal within a few days after admission and they
      were discharged from the hospital in good health within the fourth day of
      admission. One of the children ingested 97.5 mg/kg amitriptyline and probably
      died due to status epilepticus and another child who died ingested 36 mg/ kg
      amitriptyline and died due to cardiopulmonary arrest. In conclusion, our findings
      showed that initial symptoms and signs of acute amitriptyline intoxication
      appeared severe, but they disappeared with only supportive care required in most
      children except for cases that ingested high doses of drug within a few days. In
      contrast to adults, we infrequently noted respiratory insufficiency, arrhythmia
      and hypotension in children with acute amitriptyline intoxication.

PMID- 16634329
TI  - Terminalia chebula (fruit) prevents liver toxicity caused by sub-chronic
      administration of rifampicin, isoniazid and pyrazinamide in combination.
AB  - Terminalia chebula Gertn. (Combetraceae) is an important herbal drug in Ayurvedic
      pharmacopea. In the present study, a 95% ethanolic extract of T. chebula (fruit)
      (TC extract), which was chemically characterized on the basis of chebuloside II
      as a marker, was investigated for hepatoprotective activity against anti
      tuberculosis (anti-TB) drug-induced toxicity. TC extract was found to prevent the
      hepatotoxicity caused by the administration of rifampicin (RIF), isoniazid (INH)
      and pyrazinamide (PZA) (in combination) in a sub-chronic mode (12 weeks). The
      hepatoprotective effect of TC extract could be attributed to its prominent anti
      oxidative and membrane stabilizing activities. The changes in biochemical
      observations were supported by histological profile.

PMID- 16634330
TI  - Effects of excess corticosterone on NADPH generating enzymes and glucose
      oxidation in Leydig cells of adult rats.
AB  - Clinical and experimental studies have shown the adverse effects of excess
      glucocorticoid on testicular testosterone production. The NADPH co-enzyme has
      been recognized as an important factor that regulates several steps in
      steroidogenesis, while glucose oxidation acts as a limiting factor on testicular
      testosterone production. Nevertheless, the impact of excess corticosterone, the
      stress hormone on testicular NADPH availability and glucose oxidation is unknown.
      Therefore, the present study was designed to assess the specific effects of
      excess corticosterone on Leydig cell NADPH generating enzymes and glucose
      oxidation. Adult Wistar rats (200-250 g, b.w.) were treated with corticosterone
      21-acetate (2 mg/ 100 g, b.w., i.m., twice daily) for 10 days and corticosterone
      21-acetate plus luteinizing hormone (LH) (100 microg/kg b.w., i.m., daily) for 10
      days. After the treatment period, experimental animals and controls were killed,
      blood was collected and the sera separated for testosterone assay. Testes were
      removed and Leydig cells were isolated, purified and used for estimating the
      specific activity of NADPH generating enzymes and 14C-glucose oxidation. Serum
      testosterone, Leydig cellular 14C-glucose oxidation and the specific activities
      of 6-phosphogluconate dehydrogenase (6-PGDH), NADP-isocitrate dehydrogenase
      (ICDH) and malic enzyme were significantly decreased in corticosterone-treated
      rats. Co-administration of LH with corticosterone maintained the specific
      activities of 6-PGDH and ICDH and 14C-glucose oxidation at control level.
      Nevertheless, serum testosterone and Leydig cellular malic enzyme activity showed
      a significant decrease in these rats. In conclusion, the inhibitory effects of
      excess corticosterone on Leydig cell steroidogenesis are mediated through
      impaired glucose oxidation and defective NADPH generation. Co-administration of
      LH with corticosterone failed to prevent the decrease in serum testosterone and
      Leydig cell malic enzyme activity, suggesting the dominant inhibitory effects of
      excess corticosterone.

PMID- 16634331
TI  - Neuroprotective effects of Nigella sativa on experimental spinal cord injury in
      rats.
AB  - The aim of this study was to investigate the possible beneficial effects of
      Nigella sativa (NS) in comparison to methylprednisolone on experimental spinal
      cord injury (SCI) in rats. SCI was performed by placing an aneurysm clip
      extradurally at the level of T11-12. Rats were neurologically tested over 24 h
      after trauma and spinal cord tissue samples were harvested for both biochemical
      and histopathological evaluation. The neurological scores of rats were not found
      to be different in SCI groups. SCI significantly increased the spinal cord tissue
      malondialdehyde (MDA) and protein carbonyl (PC) levels, however SCI decreased
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)
      enzyme activities compared to the control. Methylprednisolone and NS treatment
      decreased tissue MDA and PC levels and prevented inhibition of SOD, GSH-Px and
      CAT enzymes in the tissues. The most significant results were obtained when NS
      was given. In SCI and placebo groups, the neurons of spinal cord tissue became
      extensively dark and degenerated with picnotic nuclei. The morphology of neurons
      in methylprednisolone and NS-treated groups were well protected, however, not as
      well as the neurons of the control group. The number of neurons in the spinal
      cord tissue of the SCI and placebo groups was significantly less than the
      control, laminectomy, methylprednisolone and NS-treated groups. In conclusion, NS
      treatment might be beneficial in spinal cord tissue damage, and therefore shows
      potential for clinical implications.

PMID- 16634332
TI  - Effects of therapeutic agents on cellular respiration as an indication of
      metabolic activity.
AB  - Animal experiments are indispensable in the investigation of the toxicity of
      drugs on cells, but may not be preferred for ethical reasons and sensitivity. As
      an alternative procedure, we investigated the susceptibility of cells to drugs
      using the effect on cellular respiration as an indicator of cell activity
      (toxicity). The primary cultures (cell lines) used in this study included human
      fetal myocardial cells, skeletal muscle cells, nerve cells, hypophyseal cells,
      epithelial cells of gastric mucosa, lymphocytes, hepatocytes, pancreatic
      (exocrine) cells, renal tubular epithelial cells and fetal adrenal cortex cells,
      which were obtained from the American Type Culture Collection (ATCC). The drugs
      used were diazepam, haloperidol and levomepromazine maleate (psychoactive drugs),
      cisplatin and doxorubicin hydrochloride (anticancer agents). The cells were used
      at a density of 2 x 10(6) cells/2 mL of growth medium and, to test the
      susceptibility, each drug was prepared at a concentration of 10 g/mL. Experiment
      results indicated that, even with the same drug, sensitivity was markedly
      different depending on the cell lines. Cardiac muscle cells showed the strongest
      respiratory inhibition by Serenace and were least inhibited by Hirnamin. The
      highest sensitivity to Cercine was noted for neurons, while gastric mucosa cells
      had almost no sensitivity. Sensitivity to Serenace, which was expected to have a
      strong nerve action, was higher in myocardial cells instead. In the present
      study, we suggested the possibility of studying individual differences in drug
      sensitivity through investigation of toxicity in each organ as opposed to
      toxicity in the individual. In addition, Serenace, which was developed as a
      neurotopic agent, showed a higher toxicity in cardiac muscle cells than in
      neurons. This finding appeared noteworthy, not only for forensic toxicology, but
      also for clinical practice and drug development.

PMID- 16634333
TI  - Non-linearities and data analysis: towards a quantitative investigation of
      delayed luminescence.
AB  - Innovative techniques for the acquisition and analysis of delayed luminescence
      (DL) signals are proposed and discussed. At a preliminary level, the signals
      prove to be a useful tool, not only for quantitative analysis, but also for
      discrimination--on theoretical grounds--among different, possibly competing,
      mechanisms responsible for DL in photosynthetic organisms. Moreover, DL
      recordings from non-photosynthetic organisms (S. cerevisiae yeast) with avalanche
      photodiode (APD) detection will be discussed.

PMID- 16634334
TI  - A framework for using epidemiological data for risk assessment.
AB  - Data on health effects from human exposure to chemicals provide the most direct
      information for risk assessment. Despite their clear relevance for risk
      assessment and despite the frequently made statements by regulatory bodies to use
      epidemiological data whenever deemed appropriate, they are not always optimally
      used. In this article, a framework for using epidemiological data in risk
      assessment is presented. Before using an epidemiologic study as the basis for
      risk assessment, its quality must be evaluated. The quality criteria for such a
      study strongly depends on the type of association between the chemical and health
      effect in terms of its specificity and latency period. The framework is built on
      the type of health effect under consideration, whether it is a specific or non
      specific effect and time window of the effect, whether it is an acute, sub-acute
      or long-term effect. Specificity and latency are aspects that have a great impact
      on the choice of research design and quality criteria that must be met in order
      to produce reliable results appropriate for risk assessment purposes. Although
      expert judgement will always play an important role, the framework can help to
      assess if a set of epidemiological data are sufficiently reliable to serve as the
      basis for the derivation of health-based exposure limits. The limitations and
      suitability to use for risk assessment of epidemiologic studies is more likely to
      be the result of poor or insufficient exposure data than of poor or unreliable
      health effect information. It is concluded that the value of epidemiologic data
      not only depends on its intrinsic quality, but also on the type of health effects
      under consideration. In this respect, the specificity and latency play an
      important role.

PMID- 16634335
TI  - Increased morbidity and mortality in acute human organophosphate-poisoned
      patients treated by oximes: a meta-analysis of clinical trials.
AB  - Organophosphates are one of the most common causes of poisoning, especially in
      the Third world, with high morbidity and mortality. The treatment of this type of
      poisoning involves the use of atropine and oximes. Atropine has been used
      successfully in large doses to counteract the muscarinic effects of
      organophosphate poisoning, but the efficacy of oximes in the management of this
      poisoning remains under question. In this study, we undertook a meta-analysis by
      reviewing all clinical trials to evaluate the efficacy of oximes in the
      management of organophosphate poisoning. The databases of PUBMED, EMBASE,
      Cochrane, SCOPUS, and the search engine of Google were searched for all clinical
      trials on the use of oximes in organophosphate poisoning. The inclusion criteria
      were death, development of intermediate syndrome, and need for ventilation. Six
      clinical trials met the inclusion criteria and were included in the metaanalysis.
      The chi2 tests for heterogeneity (P = 0.25, 0.16, and 0.33, respectively)
      indicated that the included studies were not significantly heterogeneous and
      could be combined. A significant relative risk (P = 0.0017) for death among oxime
      exposed was 2.17 (95% CI of 1.34-3.51). The 'need for ventilation' in patients
      who received oxime was higher (P = 0.03) than those who did not receive oxime
      with a relative risk of 1.53 (1.16-2.02). The incidence of 'intermediate
      syndrome' for oxime-exposed patients was significantly higher (P = 0.01) than
      oxime non-exposed patients with a relative risk of 1.57 (95% CI 1.11-2.11). It
      can be concluded that oximes are not effective in the management of
      organophosphate-poisoned patients and, surprisingly, they can be dangerous and
      worsen the patient's clinical situation.

PMID- 16634336
TI  - Toxicology in the twenty-first century.

PMID- 16634337
TI  - Why physical medicine, physical disability and physical rehabilitation? We should
      abandon Cartesian dualism.
AB  - Adjectives are supposed to describe the associated noun more fully or
      definitively, and the adjective physical is sometimes added to words such as
      medicine, rehabilitation and disability. What increase in description does its
      use allow? The adjective was probably added when rehabilitation started to
      develop for several reasons: it contrasted the mode of treatment with
      pharmacology and surgery; it contrasted the nature of the supposed aetiology with
      emotionally generated disorders, especially shell-shock; and it justified the
      presence of rehabilitation within the profession of medicine. Its continued use,
      however, perpetuates a Cartesian, dualist philosophy. This editorial uses the
      World Health Organization International Classification of Functioning (WHO ICF)
      model of illness to analyse its continued use, and concludes that its continued
      use may disadvantage both patients and the practice of rehabilitation.

PMID- 16634338
TI  - Motor relearning programme for stroke patients: a randomized controlled trial.
AB  - OBJECTIVE: To study the efficacy of the motor relearning approach in promoting
      physical function and task performance for patients after a stroke. DESIGN:
      Matched-pair randomized controlled trial. SETTING: An outpatient rehabilitation
      centre in Hong Kong. PARTICIPANTS: Fifty-two outpatients with either a thrombotic
      or haemorrhagic stroke who completed either the study or control group.
      INTERVENTIONS: The patients received 18 2-h sessions in six weeks of either the
      motor relearning programme or a conventional therapy programme. MAIN OUTCOME
      MEASURES: The Berg Balance Scale, the Timed Up and Go Test, the Functional
      Independence Measure (FIM), the modified Lawton Instrumental Activities of Daily
      Living (IADL) test, and the Community Integration Questionnaire. RESULTS:
      Patients in the motor relearning group showed significantly better performance on
      all but the Timed Up and Go Test when compared with the control group (F(1,150) =
      6.34-41.86, P < or = 0.015). The interactions between group and occasion were
      significant on all five outcome measures, indicating that the rates of change
      across time between the motor relearning and control groups differed (F(3,150) =
      3.60-33.58, P < 0.015). CONCLUSION: The motor relearning programme was found to
      be effective for enhancing functional recovery of patients who had a stroke. Both
      'sequential' and 'function-based' concepts are important in applying the motor
      relearning approach to the rehabilitation of stroke patients.

PMID- 16634339
TI  - The effectiveness of a supervised physical training model tailored to the
      individual needs of patients with whiplash-associated disorders--a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects of a physical training programme which is
      supervised and tailored to meet the needs of patients with subacute whiplash
      associated disorders. DESIGN: A randomized controlled trial with follow-up at
      three and nine months after randomization. SETTING: An interdisciplinary
      rehabilitation centre. SUBJECTS: Forty-seven patients with subacute disorders
      following a whiplash trauma. INTERVENTIONS: Patients were randomized to a
      supervised training group or a self-administered home training group. MAIN
      MEASURES: Primary outcome measures were the Self-Efficacy Scale, the Tampa Scale
      for Kinesiophobia and the Pain Disability Index. Secondary outcome measures were
      neck pain intensity, sensory and affective dimensions of pain, pain location and
      duration, muscle tenderness, grip strength, cervical mobility, sick leave and
      analgesic consumption. RESULTS: Forty patients (85%) completed the intervention
      period, and the drop-outs were followed up by intention-to-treat. The results
      showed that supervised training was significantly more favourable than home
      training, with a more rapid improvement in self-efficacy (P = 0.03), fear of
      movement/(re)injury (P = 0.03) and pain disability (P = 0.03) at three months.
      Further, supervised training significantly reduced the frequency of analgesic
      consumption (P = 0.03). The improvements were partly maintained at nine months,
      even though there was no amelioration in pain and physical disorders. Despite the
      favourable outcome, supervised intervention did not reduce sick leave.
      CONCLUSIONS: The findings indicate a treatment approach that is feasible in the
      rehabilitation of patients with subacute whiplash-associated disorders in the
      short term, but additional research is needed to extend these findings and
      elucidate treatment strategies that also are cost effective.

PMID- 16634340
TI  - Constraint-induced movement therapy in patients with stroke: a pilot study on
      effects of small group training and of extended mitt use.
AB  - OBJECTIVE: (1) To evaluate constraint-induced movement therapy for chronic stroke
      patients modified into group practice to limit the demand on therapist resources.
      (2) To explore whether extended mitt use alone may enhance outcome. DESIGN: A
      combined case-control and randomized controlled study with pre- and post
      treatment measures by blinded observers. SETTING: A university hospital
      rehabilitation department. PARTICIPANTS: Sixteen stroke patients (nine men and
      seven women; mean age 56.7 years; on average 28.9 months post stroke, five of
      whom were 6-9 months post stroke) with moderate motor impairments in the
      contralateral upper limb. INTERVENTION: Constraint-induced therapy (mitt on the
      less affected hand 90% of waking hours for 12 days) with 2-3 patients per
      therapist and 6 h of group training per day. After the training period, the
      patients were randomized either to using the mitt at home every other day for two
      week periods for another three months (in total 21 days) or to no further
      treatment. OUTCOME MEASURES: Modified Motor Assessment Scale, Sollerman Hand
      Function Test, Two-Point Discrimination test and Motor Activity Log. RESULTS: The
      mean motor performance improved significantly after two weeks of constraint
      induced group therapy on Motor Assessment Scale (1.44 (95% confidence interval
      (95% CI) 0.59-2.28) points; P = 0.003) and on Sollerman Hand Function Test (3.81
      (95% CI 0.26-7.36) points; P = 0.037) but showed no sensory change in the Two
      Point Discrimination Test (P = 0.283). The median difference in self-reported
      motor ability (Motor Activity Log) also improved (P < 0.001). However, no
      additional effect was seen from wearing a mitt for another three months.
      CONCLUSION: Constraint-induced group therapy, allowing several patients per
      therapist, seems to be a feasible alternative to improve upper limb motor
      function. The restraint alone, extended in time, did not enhance the treatment
      effect.

PMID- 16634341
TI  - Intrathecal baclofen therapy improves functional intelligibility of speech in
      cerebral palsy.
AB  - OBJECTIVE: To assess the effect of intrathecal baclofen on spastic dysarthia in
      cerebral palsy. DESIGN: Single case study. METHODS: Functional outcome measures,
      including the Assessment of Intelligibility of Dysarthric Speech, were performed
      before and after a trial of intrathecal baclofen in an adult patient with spastic
      dysarthria due to cerebral palsy. The patient proceeded to intrathecal baclofen
      pump implantation and was reassessed after six months of continuous intrathecal
      baclofen therapy. RESULTS: Improvement in function including speech
      intelligibility was seen following the intrathecal baclofen trial. The
      improvement was sustained at six months post pump implantation. CONCLUSIONS:
      Intrathecal baclofen improved functional intelligibility of speech in a carefully
      selected subject. The Assessment of Intelligibility of Dysarthric Speech was
      found to be a useful quantitative tool to assess the effect of intrathecal
      baclofen on spastic dysarthria.

PMID- 16634342
TI  - Evaluating rehabilitation using cost-consequences analysis: an example in
      Parkinson's disease.
AB  - OBJECTIVE: To use cost-consequences analysis to evaluate rehabilitation, and to
      discuss some practical limitations. DESIGN: Case study of a cost-consequences
      analysis. SETTING: Day hospital. SUBJECTS: People with Parkinson's disease
      without major cognitive loss, and their carers. INTERVENTION: A programme of
      multidisciplinary rehabilitation, delivered for one day per week over six weeks,
      and including 2 h of individual therapy (physical, occupational, speech and
      language, specialist nurse) and group activities on each occasion. MAIN MEASURES:
      COSTS: direct and overhead costs of treatment; participant travel. CONSEQUENCES:
      patient outcomes (mobility, speech and language, disability, psychological well
      being, health-related quality of life); carer outcomes (psychological well-being,
      health-related quality of life, strain); social service utilization;
      satisfaction. RESULTS: In this example the main costs were facility's overheads
      and hospital-provided transport. The consequences of the intervention were
      improved immediate outcomes for patients that diminished over four months,
      discovery of unmet social services need, high satisfaction. No benefits for
      carers were observed. CONCLUSION: A cost-consequences analysis provides a clear
      descriptive summary for decision-makers that is easier to interpret than cost
      effectiveness, cost-utility and cost-benefit analysis. It is a useful technique
      in rehabilitation research where multiple outcomes and several perspectives
      (health service, patient, carer) are relevant. However limitations remain: it is
      difficult to capture all consequences because of data deficiencies and long-term
      effects; evaluations of individual interventions are partial and do not guarantee
      economic rationality; local studies may not be generalizable; fixed protocols
      impede the evaluation of alternative service configurations.

PMID- 16634343
TI  - Effect of compensation procedures for velocity on repeatability and variability
      of gait parameters in normal subjects.
AB  - OBJECTIVE To evaluate the effects of a mathematical procedure that adjusts for
      gait velocity on the variability seen in gait analysis. DESIGN: Evaluation before
      and after compensation. SETTING: Gait laboratory, Fukui University Hospital,
      Japan. SUBJECTS: Fourteen normal volunteers. OUTCOME MEASURES: A computerized
      gait analysis system with two forceplates and a light source spot measuring
      device was used. Gait measurement in each subject was performed on three
      different days. RESULTS: The gait parameters measured on three different days
      were significantly different, particularly step length, stride length, velocity,
      the components of floor-reaction forces and hip motion. In these parameters,
      intraclass correlation coefficient, ICC (1,1) was not high (range 0.05-0.71).
      However, there was a high correlation between these parameters and velocity and
      high repeatability was obtained following compensation for velocity (ICC (1,1),
      range 0.73-0.97). In contrast, compensation of parameters whose measurement was
      not significantly different before compensation did not improve ICC (1,1).
      Variability of all parameters was acceptable, however CV (an index of
      variability) improved significantly after compensation compared with that before
      compensation in six of 15 parameters. CONCLUSIONS: Our findings suggest that low
      repeatability in gait parameters should be considered even when the gait of
      normal subjects is measured on different days. A high repeatability and more
      acceptable variability were obtained when the data were compensated for velocity.

PMID- 16634344
TI  - Implicit learning of a motor skill after mild and moderate stroke.
AB  - OBJECTIVE: To determine if adults in the subacute phase post moderate or mild
      stroke could learn a motor task under implicit practice conditions. DESIGN: Non
      randomized, between-group design. SETTING: Subjects' homes. SUBJECTS: Sample of
      convenience of 15 adults with moderate stroke, 22 adults with mild stroke, and 32
      age-matched controls. Stroke severity was determined using the Orpington
      Prognostic Scale. INTERVENTION: Practice of movements to target switches in two
      conditions, a repeated series and a random series. Practice was organized into a
      single session of six blocks of 80 trials such that blocks 1 and 2 were the
      random series, blocks 3 and 4 the repeated series, block 5 the random series, and
      block 6 the repeated series. Explicit knowledge of the two conditions was not
      provided. MAIN MEASURES: The mean response time and the coefficient of variation
      were calculated for each block for each group. RESULTS: Regardless of group,
      participants had a slower response time when practice was unexpectedly switched
      from the repeated to random condition. The response time and coefficient of
      variation for those with moderate stroke were persistently greater than those
      with mild stroke and controls, who were not different from each other.
      CONCLUSIONS: Implicit motor learning is preserved in adults with moderate stroke
      and may be a viable strategy for teaching motor skills in rehabilitation. The
      clinician should be aware that subjects with moderate stroke, even when
      performing with the less affected upper extremity, have significantly slower and
      more variable movements than those with mild stroke and controls.

PMID- 16634345
TI  - Evaluation of the effect of energy conservation techniques in the performance of
      activity of daily living tasks.
AB  - OBJECTIVE: To determine whether energy conservation techniques during common
      activity of daily living tasks actually result in lower energy expenditure, and
      to document subjective comments regarding any differences in the perceived level
      of effort. DESIGN: Descriptive study comparing energy expenditure in three tasks
      with and without energy conservation techniques, taking into account the effect
      of age. SETTING: Occupational therapy department of a rehabilitation hospital in
      Hong Kong. SUBJECTS: One hundred and eight subjects (30 < 60 years; 78 > or = 60
      years) were recruited from staff and members of an elderly social centre in the
      community. MEASUREMENTS: Energy expenditure was measured using a portable
      indirect calorimetry system for three tasks (shopping, washing clothes and
      hanging laundry) with and without energy conservation techniques. Dyspnoea,
      fatigue and perceived exertion were measured using visual analogue scales.
      RESULTS: Reduction in energy expenditure using energy conservation techniques for
      shopping and hanging laundry was documented in younger subjects only (O2
      consumption fell from 13.8 +/- 3.7 to 12.2 +/- 3.8 mL/min per kg for shopping, P
      < 0.001 and 5.9 +/- 1.2 to 5.0 -/+ 1.2 mL/min per kg, P < 0.001 for hanging
      laundry), although the older subjects experienced less perceived exertion with
      the energy conservation techniques. For washing clothes, no reduction in energy
      expenditure was observed in either age groups. CONCLUSION: Measurable benefits
      were observed with use of labour-saving equipment and avoidance of overhead
      reaching in younger subjects only.

PMID- 16634346
TI  - Longitudinal robustness of variables predicting independent gait following severe
      middle cerebral artery stroke: a prospective cohort study.
AB  - OBJECTIVE: To determine within the first 10 weeks post onset the most robust
      variables in the prediction of recovery of independent gait at six months post
      stroke. DESIGN: A prospective cohort study. SUBJECTS: One hundred and one first
      ever ischaemic middle cerebral artery stroke patients. None of these patients
      were able to walk at onset and all suffered from a marked hemiplegia. SETTING:
      Twenty-four determinants, possibly related to recovery of gait at six months,
      were measured within 14 days following stroke onset. Based on Functional
      Ambulation Categories (FAC) independent gait was classified into present (FAC >
      or = 4) or absent (FAC < 4). Bivariate logistic regression analysis was used to
      select determinants. Only significant determinants during the entire 10-week
      period were used for further weekly multivariate logistic prediction modelling of
      independent gait at six months post stroke. RESULTS: After six months post onset
      62% (N = 63) regained independent gait. Age, Barthel Index, Trunk Control Test,
      Motricity Index of arm and leg, Brunnstrom Fugl-Meyer stage of leg motor
      recovery, and type of intervention were significant determinants in bivariate
      analysis, but age of patient and Barthel Index were the most robust determinants
      in the final prediction model. Weekly re-evaluation produced sensitivity values
      between 89% and 96% and specificity values between 53% and 62%. CONCLUSION: In
      initially non-ambulatory stroke patients age and Barthel Index were the most
      robust variables during the first 10-week poststroke period in the prediction of
      independent walking at six months. However, prediction of non-ambulation at six
      months proved to be less accurate.

PMID- 16634347
TI  - Identification of healthy elderly fallers and non-fallers by gait analysis under
      dual-task conditions.
AB  - OBJECTIVE: We compared falling and non-falling healthy elderly subjects to
      identify balance disorders associated with falling. Gait parameters were
      determined when carrying out single and dual tasks. DESIGN: Case comparison
      study. SETTING: Subjects were studied in the gait laboratory at Hopital Roger
      Salengro, Lille, France. SUBJECTS: A group of 40 healthy elderly women were
      assigned to one of two groups according to their falling history: 21 fallers aged
      70.4 +/- 6.4 years and 19 non-fallers aged 67.0 +/- 4.8 years. All subjects
      performed first a single leg balance test with two conditions (eyes open/closed).
      Then, gait parameters were analysed under single-task and dual motor-task
      conditions (walking with a glass of water in the hand). MAIN MEASURES: Falls,
      number of times suspended foot touched the floor during the single leg balance
      test, cadence, speed, stride time, step time, single-support time, stride length
      and step length during walking under single- and dual-task conditions. RESULTS:
      During the single leg balance test, fallers placed their feet on the floor three
      times more often than non-fallers under eyes open conditions (P < 0.05) and twice
      as often under eyes closed conditions (P < 0.05). In the single-task condition,
      no significant difference in gait parameters was reported between fallers and non
      fallers. There was a significant difference (P < 0.05) in the gait parameters
      (cadence, speed, stride and step time, single-support time) between fallers and
      non-fallers under dual-task conditions. CONCLUSIONS: Dual tasks perturb walking
      in fallers, who exhibit deteriorated static balance. Consequently, walking under
      dual-task conditions plus a single leg balance test could be helpful in detecting
      walking disorders and planning physiotherapy to prevent falls.

PMID- 16634348
TI  - [Vitamin C decreases MMP-9 synthesis induced by hydrogen peroxide in an in vitro
      chorioamniotic membrane model].
AB  - OBJECTIVE: To evaluate the hydrogen peroxide ability to induce the synthesis of
      matrix metalloproteinase-9 (MMP-9) in an in vitro chorioamniotic membrane model.
      MATERIAL AND METHODS: An experimental, transversal, analytic and prospective
      study was made. From amniotic membranes (n = 13) of term labour pregnant women
      chorionic and chorioamniotic explants were prepared; these were stimulated with
      hydrogen peroxide [200 mcM]. A group of explants were cultured with vitamin C, 48
      hours prior to the hydrogen peroxide stimulus. Twenty-four hours after hydrogen
      peroxide stimulus the supernatants were collected and metalloproteinase-9
      production was determined by zymography methods. RESULTS: Hydrogen peroxide
      induced the synthesis of metalloproteinase-9 in chorionic and chorioamniotic
      membranes. When chorionic and chorioamniotic membranes were cultured with vitamin
      C prior to the hydrogen peroxide stimulus, the MMP-9 production diminished (p <
      0.05; Dunn's method). CONCLUSIONS: Hydrogen peroxide induced the synthesis of
      metalloproteinase-9 in chorionic and chorioamniotic membranes. When chorionic and
      chorioamniotic membranes were cultured with vitamin C, 48 hours prior to peroxide
      hydrogen stimulus, the metalloproteinase-9 production diminished with statistical
      significance.

PMID- 16634349
TI  - [Endometrial receptivity: numerical classification to successful prognosis in
      assisted reproduction programs].
AB  - BACKGROUND: Currently, the most precise way of predicting uterine receptivity is
      the histopathological study through endometrial biopsy. Endometrial morphology
      and thickness are the factors most strongly associated with better pregnancy
      rates. OBJECTIVE: To evaluate the prediction value of a numerical grade to
      predict pregnancy in patients exposed to assisted reproductive techniques.
      PATIENTS AND METHODS: 22 cycles of in vitro fertilization were made at the
      Instituto para el Estudio de la Concepcion Humana in Monterrey, Nuevo Leon, from
      June 2003 to January 2004. We evaluated and categorized: endometrial thickness
      and morphology, vascularity, miometrial ecogenicity, and uterine artery blood
      flow (including pulsatility and resistance indexes, presence of protodyastolic
      nicks, and telediastolic flow). The final numerical grade result from the sum of
      the individual values obtained for each factor. RESULTS: We included 22 cycles of
      20 patients. The general pregnancy and implantation rate was of 40 (8/20) and 26%
      (17/65) per cycle, respectively. The most common diagnosis was tube occlusion
      (28%), followed by masculine sex (24%), endometriosis (14%), anovulation (14%),
      and inexplicable (14%). There were no statistical differences among the pregnant
      and non-pregnant groups regarding: age, hormonal profile (FSH and estradiol,
      basal and at the tenth day), total of recombinant FSH unities, follicles > or =
      14 mm the day of applying human chorionic gonadotropin, aspired eggs,
      fertilization index, and transferred embryos. CONCLUSIONS: Endometrial maturity
      is essential for implantation during an assisted reproductive procedure.

PMID- 16634350
TI  - [Endometriosis and deficient intake of antioxidants molecules related to
      peripheral and peritoneal oxidative stress].
AB  - OBJECTIVE: To evaluate the antioxidant intake and the lipoperoxidation status in
      plasma and peritoneal fluid of women with endometriosis. PATIENTS AND METHODS:
      The study was carried out in 48 women with endometriosis obtained at the
      Sterility Clinic from the National Institute of Perinatology. The antioxidant
      intake was evaluated applying the Questionnaire Assessment of Antioxidants and
      Retinol Intakes in Mexican women validated by the National Institute of Public
      Health. The lipoperoxidation status was determined in plasma and peritoneal fluid
      with the malondyaldehyde method. Results were analyzed by ANOVA of Kruskal
      Wallis. RESULTS: The antioxidant intake (vitamin C, vitamin E, selenium and zinc)
      of women with endometriosis showed a significative statistical difference when
      data was compared with the control group, including total group and those
      stratified in pathology stages. The lipoperoxidation status in plasma and
      peritoneal fluid of women with endometriosis, analyzed in group, did not show
      statistical difference versus healthy women. When data was stratified according
      to the pathology severity, the percentage of lipoperoxidation status increased in
      plasma in the severe grade of endometriosis and in peritoneal fluid in the
      moderate and severe grades. CONCLUSIONS: The antioxidant intake in women with
      endometriosis showed an inverse correlation with the pathology intensity. As
      endometriosis severity intensifies, a less intake of antioxidants is present.
      There is a positive association between the pathology development and the
      lipoperoxidation status.

PMID- 16634351
TI  - [Statistical and prognostic correlation of serum levels of basal inhibin to
      response and follicular quality in assisted reproduction].
AB  - BACKGROUND: Inhibin B is a direct marker of ovarian reserve and one of the
      earliest markers of ovarian aging. It has been used in assisted reproduction
      programs as a serum marker that can identify an altered follicular reserve and
      predict a good or poor response to the stimulation with exogenous gonadotropins.
      OBJECTIVE: To correlate inhibin B levels with follicular response and quality of
      oocytes obtained through ovarian stimulation controlled in an in vitro
      fertilization cycle (IVFET), as well as relate it with variables such as:
      fertilization percentage and pregnancy rates. PATIENTS AND METHODS: In a
      prospective and transversal study we included 71 patients that entered the IVFET
      program (February-April 2005). We determined inhibin B levels at the third day of
      the cycle and evaluated the follicular response and the oocyte quality during the
      ovarian stimulation, as well as fertilization and pregnancy rates. Statistical
      analysis was made with Spearman's and ANOVA tests. RESULTS: We observed a
      positive correlation between inhibin levels and quantity of developed follicles
      (0.457), number of captured oocytes (0.390), and quantity of metaphase II oocytes
      (0.324). We observed better oocyte quality in women with inhibin levels > 251 pg/
      mL, and we considered that the ones that had levels < 50 pg/mL had poor
      follicular response (19.71%). There was no correlation with fertilization and
      pregnancy rates. CONCLUSIONS: In the early follicular phase inhibin B has direct
      correlation with ovarian reserve. Its high levels are related to better
      follicular response and oocyte quality. This enzyme levels are not useful as a
      predictive factor of pregnancy in IVFET cycles.

PMID- 16634352
TI  - [Surgical correction of vaginal agenesis].
AB  - BACKGROUND: Vaginal agenesis is a rare congenital disorder. It requires surgical
      management and still it is not defined universally. The surgical resolution of
      the pure vaginal agenesis, through fasciocutaneous pudendal thigh flaps, has few
      complications and allows the copulative function in normal conditions. OBJECTIVE:
      To assess the results of the vaginal agenesis surgical management. PATIENTS AND
      METHODS: From January 1996 to January 2005 we identified 33 patients with
      Mullerian duct and urogenital sinus disorders; eight of them had vaginal agenesis
      diagnosis. All the patients were subject to: complete medical history, karyotype
      study, determination of a complete gynecological profile, pelvic ultrasound,
      excretory urography, and, in some acute cases of hematometra or hematosalpinx, to
      an intervention with two surgical equipments: one of them used for the hematic
      collection emptiness of the internal genitals and the other one to solve the
      mechanical obstruction of vaginal agenesis. In some cases the study was completed
      through diagnostic laparoscopy. RESULTS: In our series six patients had
      functional uterus. When we made the surgical intervention we tried to make the
      uterus tunelization in the neovagina through the use of a Foley catheter.
      Nevertheless, they continued with symptoms of cyclical pelvic pain and chronic
      hematometra. One of the patients was exposed to total abdominal hysterectomy
      without bilateral oophorectomy, and in two more we are planning to make the same
      procedure in a short term. CONCLUSIONS: Fasciocutaneous pudendal thigh flaps
      technique is easy, safety and reliable, and it allows the creation of a neovagina
      in only one surgical time.

PMID- 16634353
TI  - [Changes in a semen analysis related to spontaneous pregnancy in patients with
      infertility history].
AB  - OBJECTIVE: To describe changes in a semen analysis before getting a spontaneous
      pregnancy. MATERIAL AND METHODS: In an observational, descriptive, longitudinal
      and retrospective study a semen analysis of the first evaluation of 96 patients
      was compared with the exam accomplished before getting a spontaneous pregnancy. A
      descriptive analysis of the semen exam was performed and the results of both
      exams were compared by means of at Student test with statistical significance for
      p < 0.05. RESULTS: In the first analysis, the volume, density, mobility, normal
      morphology, total number of mobile cells and total number of mobile cells with
      normal morphology (TNMCNM) were 2.45 +/- 1.39 mL, 79 +/- 43 million/mL, 40 +/-
      21%, 27 +/- 14%, 84 +/- 84 million and 23 +/- 29 million, respectively, and in
      the final analysis were 2.6 +/- 1.26 mL, 79 +/- 42 million/mL, 43 +/- 21%, 28 +/-
      14%, 97 +/- 98 million and 28 +/- 33 million, respectively. None of them were
      different. In four patients with low testosterone and a LH/FS > or = 1 ratio,
      volume increased from 1 +/- 0.31 to 1.65 +/- 0.17 mL and normal morphology from
      22 +/- 7 to 31 +/- 5. Both variables were different. In six patients with high
      prolactine and low testosterone or low FSH, density increased from 56 +/- 21 to
      114 +/- 18 million/mL and TNMCNM from 14 +/- 12 to 46 +/- 32 million. Both
      variables were different. CONCLUSION: Only those patients with low testosterone
      and a LH/FSH > or = 1 rate had an increase of semen volume and normal morphology.
      Those with high prolactine-low testosterone or high prolactine-low FSH had an
      increase of the total mobile cells and the total mobile cells with normal
      morphology. There were not changes in any semen variable of the other patients.

PMID- 16634354
TI  - [Effect of intramural and subserous myomas on in vitro fertilization cycles and
      their perinatal results].
AB  - OBJECTIVE: To evaluate the effect of intramural and subserous myomas in in vitro
      fertilization cycles, as well as its perinatal results. TYPE OF STUDY: Cases and
      controls. MATERIAL AND METHODS: All the IVF cycles between October 1999 and
      December 2004 were included. The variables of size and type of myomas, as well as
      variables of IVF cycles, implantation and pregnancy rates, and perinatal results
      were analyzed. We calculated the chi-square test to analyze the relationship
      between myomas and pregnancy. The t-Student test was used to establish the
      difference in the average between both groups regarding the studied variables. In
      the logistic regression analysis we controlled confusing variables. RESULTS: We
      analyzed 431 cycles made in 364 patients divided into two groups: study cases
      (with myomas-65 cycles) and control cases (without myomas-366 cycles). Age was
      two years older in the study group (35.7 vs 33.5, p < 0.001). There was no
      difference in: duration, type of infertility, days of stimulation, gonadotrophin
      dose, total and mature follicles, and fertilization and implantation rates. We
      only observed a difference in the recovered oocytes (8.0 vs 9.7, p = 0.027). The
      pregnancy, abortion and live-born children rates were of 20.0 vs 23.2, 46.1 vs
      29.4, and 46.1 vs 58.8%, respectively (study and control groups; p > 0.05).
      Logistic regression showed that myomas do not affect the possibility of getting
      pregnant. CONCLUSION: Intramural and subserous myomas < 5 cm do not seem to have
      an effect in the IVF cycles nor in its perinatal results. In women with myomas <
      5 cm that no dot distortion the uterine cavity it is questionable the usefulness
      of a myomectomy prior to IVF cycles.

PMID- 16634355
TI  - [Eclampsia: treatment with Veratrum viride, procaine, magnesium sulfate and
      dextrose. 1951].

PMID- 16634356
TI  - [Symmetry or asymmetry in the immune system].

PMID- 16634357
TI  - [Study of immunoglobulins, proinflammatory cytokines, lymphoproliferation and
      phagocytosis in peripheral blood of healthy young people exposed to different
      levels of atmospheric pollution].
AB  - BACKGROUND: Urban environmental pollutants, resulting from the inadequate control
      in the industries and from the use of vehicles, still represent a great danger
      for millions of people all around the world. PATIENTS AND METHOD: We made a study
      in healthy young people without family history of atopy that lived in
      Guadalajara's downtown, as well as in another group of young people who lived in
      a rural area. According to the census of the year 2000, Guadalajara city has a
      population of 4 million habitants, and a vehicle number of about a million. The
      immunological parameters that we studied were: IgG, IgA and IgM immunoglobulins
      by nephelometry, serum levels of proinflammatory cytokines IL-6, IL-1alpha, IL1
      beta and TNF-alpha by ELISAs test, and the phagocytic index in
      polymorphonuclears. The atmospheric parameters were: NO2, O3, SO2, CO and the
      suspended particles that were less than 10 micrometers (PM10). These parameters
      were obtained from a mobile unit found at the Instituto de Astronomia y
      Meteorologia de la Universidad de Guadalajara, and from an automatic station of
      environmental monitoring. RESULTS: It stands out the high concentrations of NO2
      and PM10, which in several occasions were over the standards established by the
      WHO. IgG, IgA and IgM immunoglobulins were lower in the subjects living in the
      city that in those who lived in the rural area. Phagocytic index in
      polymorphonuclears, as well as IL-1alpha levels were higher in the city group,
      though we did not find a significant difference in the immunological parameters
      analyzed in the studied groups. CONCLUSION: Environmental pollution levels found
      at Guadalajara's downtown does not modify the immunological parameters studied in
      the peripheral blood of healthy young people. This shows that this group of
      population is less vulnerable than others to the exposition of moderate levels of
      urban air pollution.

PMID- 16634358
TI  - [Allergic rhinitis. Coexistent diseases and complications. A review and
      analysis].
AB  - Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in
      the context of systemic allergic disease associated with numerous comorbid
      disorders, including asthma, chronic middle ear effusions, sinusitis, and
      lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and
      consequent behavioral and educational effects. The coexistence of allergic
      rhinitis and asthma is complex. First, the diagnosis of asthma may be confused by
      symptoms of cough caused by rhinitis and postnasal drip. This may lead to either
      inaccurate diagnosis of asthma or inappropriate assessment of asthma severity
      with over treatment of the patient. The term "cough variant rhinitis" is
      therefore proposed to describe rhinitis that manifest itself primarily as cough
      that results from postnasal drip. Allergic rhinitis, however, has also a causal
      role in asthma; it appears both to be responsible for exacerbating asthma and to
      have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation
      leads to a number of other conditions. Thus sinusitis is a frequent extension of
      rhinitis and is one of the most frequently missed diagnoses. Allergen exposure in
      the nasopharynx with release of histamine and other mediators can cause
      Eustachian tube obstruction possibly leading to middle ear effusions. Chronic
      allergic inflammation of the upper airway causes lymphoid hypertrophy with
      prominence of adenoidal and tonsillar tissue. This may be associated with poor
      appetite, poor growth, obstructive sleep apnea, mouth breathing, pharyngeal
      irritation and dental abnormalities. Allergic rhinitis is therefore part of a
      spectrum of allergic disorders that can profoundly affect the well being and
      quality of life of a child. Prospective cohort studies are required to assess the
      disease burden caused by allergic rhinitis in childhood, its consequences due to
      delay in diagnosis and treatment, and to further assess the potential educational
      impairment that may result. Because allergic rhinitis is part of a systemic
      disease process, its diagnosis and management require a coordinated approach by
      the specialist in allergy-immunology-rhinology rather than a fragmented, organ
      based approach. There are other clinical presentations such as recurrent
      infections of the upper respiratory tract, as well as pharyngeal and laryngeal
      disorders.

PMID- 16634359
TI  - [Asthma or laryngeal amyloidosis? A report of a case and literature review].
AB  - The laryngeal amyloidosis is an uncommon disease accounting for 1% of all benign
      lesions of larynx. The commonest symptom is the dysphonia, sometimes accompanied
      by stridor, laryngeal globus sensation, dysphagia and, in rare occasions, cough,
      dyspnea and hemoptysis, specially when the tracheobronchial tree is also
      affected. This paper describes the case of a 30-year-old female patient, whose
      main symptoms were progressive dysphonia and dyspnea, admitted at allergy service
      to rule out asthma. The respiratory function tests showed obstruction in the
      medium and small caliber ways without reversibility with salbutamol. Biopsies of
      ventricular band, vocal cord and arytenoid stained with positive Congo red for
      amyloid tissue, established the laryngeal amyloidosis diagnosis. The
      complementary studies to rule out amyloid tissue in the remaining
      tracheobronchial tree were negative. Dyspnea had characteristics of laryngeal
      origin, caused by a pulmonary ventilation disorder provoked by the difficult
      arrival of air to alveoli, which caused the decreased partial pressure of oxygen
      and CO2.

PMID- 16634361
TI  - [Activities of the Directive Council of the Mexican College of Clinical
      Immunology and Allergy during the period 2003-2005].

PMID- 16634360
TI  - [Hereditary angioedema. A report of a case and literature review].
AB  - Hereditary angioedema is a congenital disorder with recurrent attacks of
      localized swelling of submucosal and subcutaneous tissue, or both caused by a
      deficiency of the plasma protein C1 inhibitor. It is caused by heterozygous
      defects in the C1 inhibitor gene located on chromosome 11q, and it has an
      autosomal dominant inheritance pattern. This disease afflicts 1 in 10,000 to 1 in
      150,000 persons. Hereditary angioedema has been reported in all races, and no sex
      predominance has been found. Skin and visceral organs may be involved by the
      typically massive local edema. The most commonly involved viscera are the
      respiratory and gastrointestinal systems, and it can affect the upper airways
      resulting in severe life-threatening symptoms, including the risk of
      asphyxiation. There are three types of hereditary angioedema, which difference
      lies in the inheritance pattern and in the C1 esterase inhibitor and C4
      concentrations. The treatment is complicated and it should be treated with
      intravenous purified C1 inhibitor concentrate; corticosteroids, antihistamines
      and epinephrine can be useful adjuncts but they are not effective. We report a
      patient with hereditary angioedema type 1 and make a review of the medical
      literature.

PMID- 16634362
TI  - Atherogenesis in rheumatology.
AB  - Atherosclerosis is a chronic inflammatory disorder characterized by immune cell
      activation, inflammation driven plaque formation and subsequent destabilization.
      In other disorders of an inflammatory nature, the chronic inflammatory state per
      se has been linked to acceleration of the atherosclerotic process which is
      underlined by an increased incidence of cardiovascular disease (CVD) in disorders
      such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and
      antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation,
      additional mechanisms have been put forward that are more specific for the
      pathophysiology of the individual chronic inflammatory disorders.

PMID- 16634363
TI  - The world of biologics.
AB  - In March 2002 the National Institute for Health and Clinical Excellence (NICE)
      published guidelines for the use of anti-TNF therapy for patients with rheumatoid
      arthritis (RA). The guidelines recommended that all RA patients treated with
      these drugs should be enrolled on a national register which had been established
      by the British Society for Rheumatology (the BSRBR). A comparison cohort of RA
      patients treated with traditional disease modifying drugs (DMARDs) is also being
      recruited. The main role of the BSRBR is to study the long-term safety of
      biologic drugs. Up to the end of March 2005, 9508 patients with RA had been
      enrolled on the BSRBR. Four thousand, three-hundred and six had been treated with
      etanercept, 3561 with infliximab, 1500 with adalimumab and 141 with anakinra.
      With regards to anti-TNF drugs, 79% remained on their original drug at six
      months, 65% of whom could be classified as responders. Co-prescription with
      methotrexate was associated with a 70% response rate. Patients with a high
      baseline level of disability were less likely to respond. Overall the rates of
      serious infection were not increased in the anti-TNF versus the comparison
      cohort. However the rates of skin and soft tissue infection and of intracellular
      infections (eg, salmonella, listeria, legionella) were increased. There were 11
      cases of tuberculosis (seven extra-pulmonary). There was concern about the high
      mortality rates among patients with baseline pulmonary fibrosis treated with anti
      TNF therapy. It is unclear whether this is related to the drug or to the
      underlying disease. The rates of malignancy and mortality were not increased
      compared to the DMARD treated group in the short term. Further follow-up is
      needed to determine the long term safety of these drugs.

PMID- 16634364
TI  - Immunodeficiency in the lupus clinic.
AB  - Systemic lupus erythematous (SLE) and immunodeficiency are linked in various
      ways. For example, rare genetic complement deficiencies can pre-dispose to
      developing SLE, whilst some treatments for SLE can cause secondary
      immunodeficiencies. Various case reports describe SLE patients who have
      concomitant or later develop antibody deficiency, possibly related to
      immunosuppressive treatment, or possibly related to the lupus itself. Other
      components of the immune system, innate and adaptive may also be affected.
      Immunosuppressive treatment may also cause infections in the absence of defects
      on routine immunological testing. It is important for the clinician to be aware
      of the associations between SLE and immunodeficiency to ensure optimal
      investigation and management. This review focuses on aspects of humoral and
      cellular immunity, and their association with SLE.

PMID- 16634365
TI  - Mixed connective tissue disease.
AB  - Mixed connective tissue disease (MCTD) was first described in 1972 as a disease
      syndrome with overlapping features of systemic sclerosis, systemic lupus
      erythematosus (SLE) and polymyositis associated with antibodies to RNAse
      sensitive extractable nuclear antigen. When the antigen was subsequently
      characterized as polypeptides on the U1 ribonuclear protein component of the
      splicesosome (U1RNP), MCTD became the first rheumatic disease syndrome to be
      defined by a serologic test. Clinical features include a high frequency of
      Raynaud's syndrome, swollen hands, sclerodactyly, arthritis, polymyositis and
      interstitial lung disease. Over the last 30 years there has been a continuing
      debate as to whether MCTD constitutes a 'distinct clinical entity'. Here, I will
      review the pathological, immunogenetic and clinical features of MCTD and conclude
      that the debate remains unresolved. The early misconception that it has a
      relatively good prognosis has not stood the test of time with long-term follow-up
      studies. These have identified a tendency for MCTD to evolve into SLE or systemic
      sclerosis and highlighted pulmonary hypertension and scleroderma renal crisis as
      important causes of death. Providing it is realized that our appreciation of the
      clinical features associated with anti-U1RNP have evolved over time, MCTD remains
      a useful concept in clinical practice. Whether it can be credited with the term
      'disease' awaits the demonstration of common etiopathological events underlying
      the development of antibodies to U1 RNP and their associated clinical features.

PMID- 16634366
TI  - Connective tissue associated pulmonary arterial hypertension.
AB  - The number of publications in the field of pulmonary hypertension has increased
      exponentially over the past 10 years. As a consequence our understanding of the
      condition has advanced enormously. Pulmonary hypertension is now recognised as an
      uncommon and treatable disease, rather than a rare lethal disease. Progress in
      the field of connective tissue disease associated pulmonary hypertension has been
      less consistent. This paper covers the most influential published data on
      connective tissue associated pulmonary hypertension, and adds some insights from
      data available on file with pharmaceutical companies and from our database at the
      Royal Free Hospital. The following conclusions may be drawn. First, the
      prevalence of pulmonary hypertension associated with connective tissue diseases
      is lower than generally accepted. Second, the natural history and prognosis, at
      least in the setting of systemic sclerosis, is worse than seen in patients with
      idiopathic pulmonary hypertension. Finally, widespread and timely availability of
      disease modifying therapies substantially improves the prognosis for patients
      with systemic sclerosis associated pulmonary hypertension, in the treatment
      population and consequentially in the population as a whole. Identifying patients
      with very early disease and analysing the drivers for disease progression, is the
      key to further progress. Early diagnosis is most readily achieved in patients
      with connective tissue disease associated pulmonary hypertension. This represents
      an opportunity for those with an interest in academic rheumatology.

PMID- 16634367
TI  - Primary systemic vasculitis: treatment of difficult cases.
AB  - The primary systemic necrotizing vasculitides are a severe group of diseases,
      which untreated have a high mortality. The majority respond to treatment with
      high dose steroids and cyclophosphamide, however a significant proportion of
      those treated suffer morbidity due to the side effects of these agents, and a
      number of patients are refractory to treatment. We review and discuss alternative
      and emerging treatment options for patients who fail or cannot tolerate
      conventional therapy. An interesting subgroup of patients with systemic
      vasculitis and antiphospholipid antibodies provides an additional diagnostic and
      therapeutic challenge. We review what is known about this subgroup, and suggest
      screening for antiphospholipid antibodies in all patients with systemic
      vasculitis.

PMID- 16634368
TI  - Lupus nephritis and renal disease in pregnancy.
AB  - Management of pregnant women with renal disease involves awareness of, and
      allowance for, physiological changes including decreased serum creatinine and
      increased proteinuria. For women with systemic lupus erythematosus (SLE),
      pregnancy increases likelihood of flare. These can occur at any stage, and are
      more difficult to diagnose, as symptoms overlap those of normal pregnancy. Renal
      involvement is no more common in pregnancy. Worsening proteinuria may be lupus
      flare but differential includes pre-eclampsia. In women with chronic renal
      disease, pregnancy may accelerate decline in renal function and worsen
      hypertension and proteinuria, with increased risk of maternal (eg, pre-eclampsia)
      and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of
      renal impairment peri-conception. Pregnancy success rate varies from 20% to 95%
      depending on base-line creatinine. Best outcome is obtained if disease was
      quiescent for >6 months pre-conception. Women on dialysis or with renal
      transplants can achieve successful pregnancy but have higher maternal and fetal
      complication rates. Acute on chronic renal failure can develop secondary to
      complications such as HELLP and AFLP. Management needs to be by a
      multidisciplinary team involving physicians and obstetricians, ideally beginning
      with pre-pregnancy counselling. Treatment of flares includes corticosteroids,
      hydroxychloroquine, azothioprine, NSAIDs and MME Blood pressure is controlled
      with methyldopa, nifedipine or hydralazine.

PMID- 16634369
TI  - Pregnancy, lupus and antiphospholipid syndrome (Hughes syndrome).
AB  - Autoimmune diseases (AD) occur frequently in women during their childbearing
      years and may influence pregnancy outcome and neonatal health. Patients with
      systemic lupus erythematosus (SLE) can experience a disease flare-up during
      pregnancy with potential negative effects on the product of conceptus, especially
      if the disease is active. Recurrent pregnancy loss is now considered as a
      treatable clinical condition associated with the presence of circulating
      antiphospholipid antibodies (aPL). The neonatal lupus syndromes (NLS), caused by
      the transplacental passage of maternal IgG anti-Ro/SS-A and anti-La/SS-B
      antibodies to the fetus, carry significant morbidity and mortality in case of
      cardiac manifestations. Immunosuppressive agents are often administered during
      pregnancy in order to control maternal disease and to ensure a better pregnancy
      outcome. Nowadays, owing to our increasing knowledge of the disease
      pathophysiological mechanisms and the development of combined medical-obstetric
      clinics, pregnancy outcome in patients with AD has notably improved.

PMID- 16634370
TI  - Antiphospholipid syndrome and tissue factor: a thrombotic couple.
AB  - The antiphospholipid syndrome (APS) is characterized by thrombosis and/or
      pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Among
      the thrombogenic mechanisms proposed, it has been suggested that aPL can
      stimulate tissue factor (TF) expression by endothelial cells (ECs) and monocytes.
      Moreover, our in vivo studies have shown that APS patients (particularly those
      with thrombosis) have increased monocyte TF expression. Yet, the molecular
      mechanism(s) by which aPL induce TF expression has not been completely
      underscored. In a recent study, we have demonstrated that aPL induces TF
      expression in monocytes from APS patients by activating, simultaneously and
      independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase
      depenent nuclear translocation and activation of NFkappaB/Rel proteins.
      Understanding the intracellular mechanism(s) of aPL-mediated monocyte activation
      may help to establish new therapeutic approaches, such as selective inhibition of
      MAP kinases, to reverse the prothrombotic state in APS. Furthermore, the
      contribution of TF to a protrombotic state in the APS provides a renewed focus on
      antithrombotic therapies in current use, including the oral anticoagulation and,
      more recently, the use of statins, which have been proven to be effective in the
      inhibition of EC and monocyte TF-expression.

PMID- 16634371
TI  - Anticoagulation via anti-Factor Xa inhibition.
AB  - Hospital-acquired deep vein thrombosis (DVT) affects 10-25% of medical patients
      and up to 60% of surgical patients. While thromboprophylaxis is without a doubt
      under utilized in the hospital setting, there is also a need for more efficacious
      agents. Fondaparinux, the first of a new class of agents Factor Xa inhibitiors,
      has recently come into clinical use. It is a synthetic pentasaccharide and
      indirect Factor Xa inhibitor with a predictable antithrombotic action. Being a
      synthetic product, there are no concerns about supply, nor viral or prion protein
      contamination. Initial large international trials in orthopaedic patients
      demonstrated its superior efficacy to standard thromboprophylaxis. Further trials
      confirmed its superior efficacy in venous thromboembolism (VTE) prevention, both
      in medical and surgical patient groups, as well as treatment of pulmonary
      embolism and DVT. Its use has also recently been evaluated in acute coronary
      syndromes and angioplasty. Fondaparinux currently has licenses in the UK for
      thromboprophylaxis and treatment of VTE and a license for the management of acute
      coronary syndrome is likely to be forthcoming. It has a favourable side effect
      profile and if the price is acceptable, is likely to take over from low molecular
      weight heparins in these indications as the drug of choice on the grounds of
      efficacy and safety.

PMID- 16634372
TI  - Laboratory diagnosis and management challenges in the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or
      venous thrombosis and pregnancy morbidity manifested by early or late losses.
      Laboratory diagnosis ofAPS relies on the demonstration of a positive test for
      antiphospholipid antibodies (aPL). In clinical practice, the gold standard tests
      are those that detect anticardiolipin antibodies (aCL) and/or the lupus
      anticoagulant (LA). Although other specificities for aPL have been described
      their clinical utility and standardization has still to be established.
      Persistence of aPL positive tests must be demonstrated, and other causes and
      underlying factors considered. Although it is universally recognized that the
      routine screening tests (aCL and/or LA) might miss some cases, careful
      differential diagnosis and repeat testing are mandatory before the diagnosis of
      'seronegative APS' can be made. Correct identification of patients with APS is
      important, because prophylactic anticoagulant therapy can prevent thrombosis from
      recurring, and treatment of affected women during pregnancy can improve fetal and
      maternal outcome.

PMID- 16634373
TI  - Mycophenylate mofetil: what role in the treatment of lupus?
AB  - Improved patient survival following lupus nephritis with the institution of
      corticosteroids, immunosuppressants and renal replacement therapy allows greater
      emphasis on long-term management issues. In particular, the recent focus has been
      on therapies to treat nephritis with fewer adverse effects of cyclophosphamide
      including immunosuppressive regimens. Mycophenolate mofetil (MMF) has been used
      in the field of transplantation for more than 10 years. Following initial
      anecdotal reports describing benefits of MMF in the treatment of lupus nephritis,
      randomized, controlled trials have established a role for MMF in the treatment of
      lupus nephritis. MMF use to treat other lupus manifestations has been evaluated
      only in anecdotal case reports or series with few well-designed trials. Issues
      complicating clinical trial design in lupus including appropriate use and
      interpretation of activity and damage indices, comparable remission and response
      criteria and stratification of high risk populations have been the subject of
      much discussion and emerging consensus. As long-term outcomes in lupus improve,
      the toxicity of therapy and risk of relapse become increasingly important
      determinants of choice of therapeutic agents.

PMID- 16634374
TI  - Prediction and prevention of autoimmune diseases: additional aspects of the
      mosaic of autoimmunity.
AB  - Autoimmune connective tissue diseases are chronic, potentially life threatening
      complex multisystem disorders. Their etiology is unknown but genetic, hormonal
      and environmental factors are important. The clinical disease is preceded by a
      long period of time (sometimes many years) when the patients can be identified by
      characteristic antibodies in their serum. When such a patient is identified he is
      usually followed and treated if clinical disease manifests itself. However, other
      factors besides the existence of autoantibodies have a predictive value for those
      disorders; some of them hereditary or genetic, and can be used only to predict
      likelihood of future disease, and others, connected to lifestyle and environment,
      could be modified in order to try and prevent it. Several non-randomized small
      scale studies have suggested that autoimmune disease could be prevented if
      treated aggressively prior to manifestations of symptoms. However, if such is the
      case, criteria would have to be formalized for selection of patients for this
      preventive treatment. Only patients whose probability to develop clinical disease
      is higher then a certain threshold should be treated while asymptomatic. The aim
      of this article is to review the major risk factors for autoimmune disease, both
      hereditary and environmental, and so to help define those future criteria.
      Individuals who are at risk to develop an autoimmune disease should be advised to
      refrain from activities and lifestyle which endangers their health and quality of
      life.

PMID- 16634375
TI  - Give depression among elderly the urgency it deserves.

PMID- 16634376
TI  - Innovative CF program responds to the unique needs of adults.
AB  - The median age of survival among CF patients has risen from 14 to nearly 40 over
      the past three decades, but these individuals have many different medical and
      psychosocial needs than the pediatric population. To better meet these needs,
      Atlanta-based Emory University Medical School has developed a distinct program
      for adult patients that provides multidisciplinary care to older CF patients from
      throughout the Southeast.

PMID- 16634377
TI  - New Web-based program gets patients primed for DM.
AB  - Recognizing that a large percentage of chronically ill patients are simply not
      ready or willing to make meaningful behavioral changes, Ann Arbor, MI-bases
      HealthMedia has developed a Web-based program aimed at getting these patients to
      the point where they can take full advantage of the benefits that traditional DM
      programs have to offer. It's an automated but personalized approach, and early
      results suggest it is making an impact.

PMID- 16634378
TI  - Low-cost therapies deliver big impact in cardiac care.
AB  - That's the conclusion of two new studies that looked at different aspects of
      heart disease. Both found that low-cost pharmaceutical agents offer substantial
      preventive impact, but both also determined that there is ample room for
      improvement in prescribing patterns. One other intriguing result: higher spending
      does not necessarily correlate with higher quality or better outcomes.

PMID- 16634379
TI  - Exploring parental reactions to the diagnosis of cleft lip and palate.
AB  - The birth of an infant with a facial cleft evokes a range of emotions and
      reactions in parents. During acceptance of a child's disability, parents are said
      to progress through several stages similar to those responses reported in the
      bereavement process. This paper describes the process of adapting in terms of
      personal construct theory, and reports a pilot of the repertory grid technique as
      a therapeutic tool to elicit parental reactions following diagnosis of cleft lip
      and palate. Two mothers compared other significant life events to their reactions
      to the diagnosis of cleft lip and palate. This pilot supported the use of the
      repertory grid technique as a means to facilitate exploration of parental
      responses. Comparisons to the bereavement process were evident, although
      individual reactions or perceptions may differ from those expected.
      Recommendations are made for a wider research study within cleft lip and palate.

PMID- 16634380
TI  - Staff views of a deliberate self-harm protocol for children and young people.
AB  - An audit to evaluate a protocol for the management of children and young people
      presenting with self-harm was undertaken at Calderdale and Huddersfield NHS
      Trust. The objectives were to review current practice and to identify strengths
      and challenges. The audit showed that most staff were aware of the written
      procedure for obtaining a specialist assessment by the child and adolescent
      mental health services (CAMHS), but that feedback was inconsistent and there was
      a need for improved communication between health professionals.

PMID- 16634381
TI  - Nurse-led paediatric pre operative assessment: an equivalence study.
AB  - AIM: to explore whether nurses can undertake the pre operative assessment of
      children prior to day case surgery as safely as senior house officers. DESIGN: a
      randomised controlled trial involving 595 children, using an equivalence
      methodology (a method which looks for similarity rather than a significant
      difference). Pre-operative assessment prior to day case surgery was randomised to
      either a nurse (experimental group) or a junior doctor (control group). Blinded
      expert verification of nurse/junior doctor performance was ascertained by an
      experienced anaesthetist (the 'gold standard'). RESULTS: there was equivalence
      between nurses and senior house officers in their ability to detect clinically
      significant abnormalities within the sample population. Subgroup analysis also
      demonstrated equivalence in respect of history taking abilities. The smaller
      number of clinically significant physical findings within the sample meant that
      equivalence in respect of physical examination remains uncertain. Although the
      study was limited to a single setting, the results demonstrate nurses'
      equivalence with junior doctors in a discrete paediatric context.

PMID- 16634382
TI  - Sure Start community children's nursing: Setting up a minor illness and injury
      service for children up to five years.
AB  - A feasibility study was carried out in a Sure Start area to examine ways of
      implementing the 'improving health' Sure Start target to reduce the numbers of
      children aged up to five years being admitted to hospital with gastroenteritis,
      respiratory infection and severe injury. As a result of the study's
      recommendations a community children's nurse was employed as part of the Sure
      Start team to support families caring for children with minor illnesses or
      injuries at home. The pilot scheme has been well received by the local community,
      and families report a reduced reliance on hospital and GP services.

PMID- 16634383
TI  - Intravenous drug administration: a skill for student nurses?
AB  - This article explores issues related to children's nursing students learning
      about preparation and administration of IV drugs, considering professional and
      organisational issues. The competencies required for safe practice are discussed,
      and the question of who is in the best position to teach and assess students in
      this skill is considered. Organisations need to ensure that clear guidelines
      exist for student nurses' involvement in IV therapy.

PMID- 16634384
TI  - Comparison of ethyl chloride spray with topical anaesthetic in children
      experiencing venepuncture.
AB  - AIM: Initial validation of ethyl chloride spray in minimising pain for children
      experiencing venepuncture in comparison to Ametop cream. DESIGN: A randomised non
      inferiority cross-over trial comparing ethyl chloride with Ametop in 77 children
      aged five to 13 years undergoing measurement of glomerular filtration rate.
      Additional data were gathered on the child's preferred choice for the third
      venepuncture. RESULTS: Ethyl chloride spray is of equal preference to Ametop in
      children experiencing venepuncture, with lower self-reported pain score. It
      should be considered as an added alternative option to topical anaesthetic but
      further work is needed to clarify application technique.

PMID- 16634385
TI  - Understanding some naturalistic research methodologies.
AB  - This article aims to redress the confusion surrounding the meaning of research
      terms. While most textbooks outline the meanings of different research terms in a
      way that is very abstract for many readers, this article has taken the opposite
      approach. It outlines a fictitious scenario and uses it to explain some of the
      more common research terms from the naturalistic paradigm - research data
      collected within the natural setting such as an outpatients clinic or health
      centre, as opposed to a controlled laboratory setting. This type of research is
      often referred to as qualitative research.

PMID- 16634386
TI  - Back to basics.

PMID- 16634387
TI  - Malnutrition: the real eating problem.

PMID- 16634388
TI  - Ask the experts. Older people with mental health problems in acute care settings.

PMID- 16634389
TI  - Taking a break.

PMID- 16634390
TI  - Developing practice for healthy ageing.
AB  - The Foundation of Nursing Studies together with Pfizer Ltd has set aside
      susbtantial funds to reinforce the role of nursing in health promotion for older
      people. This article describes the work of the four teams selected from across
      Enlgand to take part in the Developing Practice for Healthy Ageing Programme.

PMID- 16634391
TI  - A new service in the intermediate care of older adults with mental health
      problems.
AB  - This article describes the a new multidisciplinary, nurse-led service for older
      adults with mental health problems, the Home Treatment Team (HTT) which has just
      begun in the Older Adults Directorate of Central and North West London Mental
      Health Trust (CNWL). The team aims to provide mental health care and treatment in
      the home for adults aged over 65, offering an alternative to hospital admission
      and facilitating early discharge. These functions place the service in the
      intermediate care category (Department of Health (DH) 2001), an area which is not
      well documented in the care of older people with mental health needs.

PMID- 16634392
TI  - Medication errors: professional issues and concerns.
AB  - In the UK, medication errors are a growing problem. Dobrzanski et al (2002)
      estimated that in one trust the incidence of medication error ranged between 35
      to 70 per cent. Such high estimations are a cause for concern, particularly when
      the administration and supply of medicines, which directly involves nurses, can
      contribute to the cause of medication error. Part of the National Patient Safety
      Agency's (NPSA) role is monitoring medication errors in hospitals. Although the
      NPSA can provide information on drug alerts that target primary care
      organisations, obtaining accurate figures for medication errors is more
      difficult. Medication errors can be extremely harmful for older people, therefore
      nurses who prescribe or administer medicines should be assessed for mathematical
      competence, but also be aware of the potential problems that can arise from
      medication errors (Banning 2005).

PMID- 16634393
TI  - Promoting urinary continence in older people.

PMID- 16634394
TI  - Strategic working.

PMID- 16634395
TI  - [Children's farms in The Netherlands: hygiene and zoonotic pathogens].
AB  - In 2004 the Food and Consumer Product Safety Authority (VWA) investigated the
      hygiene and hygiene facilities on 125 children's farms. In general, both the
      level of hygiene and the availability of hygiene facilities were good. A previous
      investigation, carried out in 2002, had highlighted a number of points for
      improvement, such as the need to improve hand-washing facilities. While the
      situation was better in 2004, it still did not meet the standard laid down by the
      VWA. The VWA aspires to achieve 100% implementation of the requirement that
      children's farms have a Code for Hygiene and an information board. Investigation
      of faecal samples collected in 2002 showed the presence of STEC O157 on 13
      (10.2%) of the visited farms, Salmonella spp. on 19 (14.5%) and Campylobacter
      spp. on 74 (56.6%). These results show that there is a real risk of becoming
      infected with a zoonotic pathogen when visiting a children's farm. This
      emphasizes the importance of strict adherence to hygiene measures by workers and
      visitors on children's farms in The Netherlands.

PMID- 16634396
TI  - [Diverse interests in the swine industry].

PMID- 16634397
TI  - [Surgery and Internal Diseases are crucial specialties, you absolutely can't miss
      them. Interview by Marianne M. Sloet van Oldruitenborgh-Oosterbaan].

PMID- 16634398
TI  - [Worms in the clinic].

PMID- 16634399
TI  - [Information about avian influenza].

PMID- 16634400
TI  - [The current buyer's right and the position of the veterinarian].

PMID- 16634401
TI  - Oral health consequences of experimenting with tobacco and oral piercing.

PMID- 16634402
TI  - New therapies on the horizon for allergic rhinitis.

PMID- 16634403
TI  - Diabetes research concerning children.

PMID- 16634404
TI  - Soft drinks: the liquid candy.

PMID- 16634405
TI  - Living my life: a young woman's story of the challenges of spina bifida.

PMID- 16634406
TI  - More than just a cough: pertussis, and the nurse's role in school and community
      health.

PMID- 16634407
TI  - Transition points: helping students start, change, and move through the grades.

PMID- 16634408
TI  - Breaking down the categories.

PMID- 16634409
TI  - The sinking brain: how to measure consciousness in anaesthesia.

PMID- 16634410
TI  - Unconsciousness.
AB  - This paper reviews a theory on the physiological conditions of consciousness. The
      theory consists of four hypotheses: (1) The occurrence of states of consciousness
      depends on the formation of higher-order representations that represent the
      internal state of the brain itself. (2) Higher-order representations are
      instantiated by the spatio-temporal activity pattern of large-scale neuronal
      assemblies. (3) The N-methyl-D-aspartate (NMDA) synapse plays a crucial role in
      the generation of conscious states by implementing the binding mechanism that the
      brain uses to produce large-scale assemblies. (4) The activation state of the
      NMDA receptor determines the rate at which representational structures can be
      built up. Unconsciousness or altered states of consciousness occur if, and only
      if, NMDA-dependent binding processes are inhibited.

PMID- 16634411
TI  - Anaesthesia defined (gentlemen, this is no humbug).
AB  - Our charge was to define anaesthesia as produced by inhaled anaesthetics. A
      definition may be useful to an understanding of the anaesthetic state, and it may
      guide studies of the mechanisms by which anaesthesia is produced. All inhaled
      anaesthetics act on the central nervous system to produce two reversible
      conditions, immobility and amnesia, that define the anaesthetic state. No other
      reversible, clinically useful, conditions are essential to the definition. Some
      conditions are unmeasurable (unconsciousness), not present for all inhaled
      anaesthetics (relaxation), or are not present at anaesthetizing concentrations
      (suppression of autonomic reflexes.) One (analgesia) is unmeasurable (the
      anaesthetized patient cannot tell an investigator that he/she hurts or does not
      hurt), and surrogate measures (increases in breathing, blood pressure, and heart
      rate with surgery) suggest that some pain is perceived. These and myriad other
      changes produced by inhaled anaesthetics are side effects; they do not define
      anaesthesia; only immobility and amnesia supply such a definition.

PMID- 16634412
TI  - Concepts of EEG processing: from power spectrum to bispectrum, fractals,
      entropies and all that.
AB  - Over the past two decades, methods of processing the EEG for monitoring
      anaesthesia have greatly expanded. Whereas power spectral analysis was once the
      most important tool for extracting EEG monitoring variables, higher-order
      spectra, wavelet decomposition and especially methods used in the analysis of
      complex dynamical systems such as non-linear dissipative systems are nowadays
      attracting much attention. This chapter reviews some of these methods in brief.
      However, a comparison of some of the newer approaches with the more traditional
      ones with respect to clinical end-points by association measures and to the
      signal-to-noise ratio raises some doubt over whether the newer EEG-processing
      techniques really do better than the more traditional ones.

PMID- 16634413
TI  - Processed EEG in natural sleep.
AB  - Sleep stages are conventionally scored according to recommendations by a
      committee chaired by Rechtschaffen and Kales in 1968. With these rules normal
      sleep is divided into rapid eye movement sleep and non-rapid eye movement sleep.
      Non-rapid eye movement sleep is subdivided into four further stages. With the
      Rechtschaffen and Kales scoring system the dominant sleep stage at any one time
      is scored. However, the dynamic structure of sleep is not adequately shown.
      Furthermore, there is considerable interscorer variability, the scoring is time
      consuming, tedious and difficult to perform. To overcome these limitations
      automatic sleep scoring devices using processed EEG technology are developed.
      These developments are discussed in this chapter.

PMID- 16634414
TI  - Altered states of consciousness: processed EEG in mental disease.
AB  - Due to increasing life expectancy and a rising elderly population in Europe, the
      incidence of mild cognitive impairment which may predict diseases like
      Alzheimer's Disease or Vascular Dementia, is rising. Neurophysiological
      techniques are simple and inexpensive tools for early diagnosis and provide
      useful and objective correlates of cognitive activity both in normal subjects and
      patients suffering from the above conditions. Cognitive impairment due to
      different mental disease is characterized by decreased power and coherence in the
      alpha/beta band, which suggests functional disconnection among cortical areas,
      whereas both power and coherence in the delta and theta bands increase as a sign
      of cortical deafferentation from subcortical structures. Quantification of power
      and phase relationship by bispectral analysis suggests the Bispectral Index could
      be a useful but simple tool for early diagnosis of mental disease.

PMID- 16634415
TI  - Special cases: ketamine, nitrous oxide and xenon.
AB  - Most general anaesthetic agents produce anaesthesia by increasing the activity of
      inhibitory gamma-aminobutyric acid type A receptors. The effects of ketamine,
      xenon and nitrous oxide on these receptors are, however, negligible. These
      anaesthetic agents potently inhibit excitatory N-methyl-D-aspartate receptors.
      Although these anaesthetic agents display some similar clinical features, such as
      potent analgesic effects, there are some important differences. Ketamine and
      nitrous oxide produce sympathomimetic effects, whereas xenon produces a
      sympatholytic effect. In addition, these anaesthetic agents return differential
      signals on clinical available anaesthetic depth monitors such as the bispectral
      index and mid-latency auditory evoked potential. Ketamine and nitrous oxide do
      not per se decrease the bispectral index. However, xenon decreases the bispectral
      index in a concentration-dependent manner. Similarly, ketamine and nitrous oxide
      do not suppress the mid-latency auditory evoked potential whereas xenon does.
      Thus, anaesthetic depth monitors fail to describe consciousness accurately when
      ketamine and nitrous oxide are used.

PMID- 16634416
TI  - Update on bispectral index monitoring.
AB  - Since 1997, bispectral index (BIS; Aspect Medical Systems Inc., Natick, MA) has
      been in clinical practice and a wealth of experimental research has accumulated
      on its use. Originally, the device was approved only for monitoring hypnosis and
      has now received an indication for reducing the incidence of intraoperative
      awareness during anesthesia. Numerous studies have documented the ability of BIS
      to reduce intermediate outcomes such as hypnotic drug administration, extubation
      time, postoperative nausea and shortened recovery room discharge. Two recent
      large-scale outcome studies using BIS (one randomized controlled trial and one
      prospective, nonrandomized historical cohort study) identified an approximately
      80% reduction in the incidence of recall after anesthesia. BIS provides
      clinicians with unique information that can be used to tailor hypnotic drug doses
      to individual patient requirements. BIS does not predict movement or hemodynamic
      response to stimulation, nor will it predict the exact moment consciousness
      returns. This review will also discuss other BIS applications including use in
      pediatrics, intensive care and for procedural sedation. Some limitations exist to
      the use of BIS and it is not useful for some individual hypnotic agents
      (ketamine, dexmedetomidine, nitrous oxide, xenon, opioids). BIS technology is
      moving out of the operating room and into diverse environments where conscious
      and deep sedation are provided. Anesthesiologists need to be actively involved in
      promoting patient safety and helping transition this technology into broader use.

PMID- 16634417
TI  - Entropy.
AB  - The concept of entropy, originally derived from thermodynamics, has been
      successfully applied to EEG analysis. Various entropy algorithms have been used
      in clinical studies, but until now a commercially available monitor exists only
      for spectral entropy. By calculating two distinct values for the EEG dominated
      part of the spectrum (state entropy, SE) and the total spectrum (response
      entropy, RE), the M-Entropy module claims to provide useful information regarding
      the cortical state of the patient as well as an indirect measure of adequacy of
      analgesia. Generally, entropy has been studied for quantification of anaesthetic
      drug effect for various GABA-ergic i.v. induction agents and volatile
      anaesthetics like propofol and sevoflurane and overall was found comparable to
      the current clinical gold standard bispectral index (BIS). Entropy guidance may
      not be used during ketamine or nitrous oxide administration, since there is no
      reliable correlation to the patient's state of consciousness. The usefulness of
      RE as a surrogate for increased EMG activity due to painful stimulation has not
      been proven so far.

PMID- 16634418
TI  - The Narcotrend monitor.
AB  - The Narcotrend (MonitorTechnik, Bad Bramstedt, Germany) is an EEG monitor
      designed to measure the depth of anaesthesia. It has been developed at the
      University Medical School of Hannover, Germany, has been commercially available
      for 5 years and has meanwhile received US Food and Drug Administration approval.
      The Narcotrend algorithm is based on pattern recognition of the raw
      electroencephalogram (EEG) and classifies the EEG traces into different stages
      from A (awake) to F (increasing burst suppression down to electrical silence).
      The newest Narcotrend software version includes a dimensionless Narcotrend index
      from 100 (awake) to 0 (electrical silence). The raw EEG signal can be recorded by
      standard electrocardiogram electrodes for single- and double-channel
      registration. The Narcotrend monitor provides a vast amount of information: the
      actual Narcotrend stage and index, the trend ('cerebrogram'), the raw EEG signal
      and a power spectrum and several derived EEG parameters. Multiple clinical and
      validation studies are available for the Narcotrend monitor, including
      comparisons with the BIS monitor (Aspect Medical Systems, Natick, USA).

PMID- 16634419
TI  - Patient state index.
AB  - The patient state index (PSI) is a clinically validated measure of the effect of
      anaesthesia and sedation. The PSI is calculated via a proprietary algorithm by a
      high-resolution 4-channel electroencephalograph (EEG) monitor after advanced
      artifact rejection. The PSI has been designed specifically for intra-operative
      and intensive care use to monitor patient sedation and drug effect. The algorithm
      relies on EEG power, frequency and phase information from anterior-posterior
      relationships of the brain as well as coherence between bilateral brain regions.
      The EEG monitor, initially called the PSA4000, is also the SEDLine monitor, the
      newest generation of the device. The SEDLine system provides the clinician the
      option of storing and downloading patient data for future use as well as
      monitoring bilateral brain function and symmetry with a density spectral array
      (DSA) display.

PMID- 16634420
TI  - Auditory evoked potentials.
AB  - This chapter will focus on the two auditory evoked potentials (AEP) most commonly
      used to assess the effects of general anesthetics on the brain, the auditory
      middle latency response (AMLR) and the 40 Hz auditory steady-state response (40
      Hz-ASSR). We will review their physiological basis, the recording methodology,
      the effects of general anesthetics, their ability to track changes in level of
      consciousness and their clinical applications. Because of space constraints, this
      review will be limited to human studies.

PMID- 16634421
TI  - Monitoring methods: SNAP.
AB  - The SNAP electroencephalogram (EEG) monitor, described as an interesting,
      innovative EEG tool that samples raw EEG signals and uses its own unique
      algorithm, analyses both high- (80-420 Hz) and low- (0-20 Hz) frequency
      components of the signal. This is termed the SNAP index, and it ranges from 100
      (arbitrarily representing the fully awake state) to 0 to provide functional data
      points for patient management. The SNAP is the first commercial EEG-monitoring
      tool to use Personal Digital Assistant computer technology. The first version of
      SNAP index was introduced in 2002, and so far there has been little experience
      with the SNAP device reported in the literature. Compared with other EEG devices,
      there is no evidence that SNAP is superior to others in generating more specific
      information about 'depth of sedation'. Moreover, the influence of high-frequency
      electromyographic activity on the SNAP needs to be clarified.

PMID- 16634422
TI  - Classic electroencephalographic parameters: median frequency, spectral edge
      frequency etc.
AB  - Even today many anaesthesiologists rely on parameters of the autonomic nervous
      system, such as blood pressure and heart rate to decide if a patient is
      adequately anaesthetized. It is thought that the electroencephalogram (EEG) may
      provide more information on the state of anaesthesia. Because full EEG analysis
      is not possible in the operating room, processed EEG parameters have been
      developed comprising complex information into a single value. Time and frequency
      domain parameters are calculated. The power spectrum results from a Fourier
      analysis and can be described by parameters such as median frequency, spectral
      edge frequency and others. It was noted, however, that anaesthetics at low doses
      increase frequency of the EEG, whereas at high doses the EEG is depressed. This
      biphasic response makes it difficult to clearly distinguish the exact anaesthetic
      state of a patient. Median frequency and spectral edge frequency have been
      studied in numerous studies. However, no sole indicator has been derived from the
      EEG that could serve as a descriptor of anaesthetic depth.

PMID- 16634423
TI  - Monitoring analgesia.
AB  - Analgesia (pain relief) amnesia (loss of memory) and immobilisation are the three
      major components of anaesthesia. The perception of pain, and therefore, the need
      for analgesia, is individual, and the monitoring of analgesia is indirect and, in
      essence, of the moment. Under general anaesthesia, analgesia is continually
      influenced by external stimuli and the administration of analgesic drugs, and
      cannot be really separated from anaesthesia: the interaction between analgesia
      and anaesthesia is inescapable. Autonomic reactions, such as tachycardia,
      hypertension, sweating and lacrimation, although non-specific, are always
      regarded as signs of nociception or inadequate analgesia. Autonomic monitoring
      techniques, such as the analysis of heart rate variability, laser Doppler
      flowmetry, phlethysmographically derived indices and the pupillary light reflex,
      may help to quantitate reactions of the autonomic nervous system. For the past
      few years, automated electroencephalographic analysis has been of great interest
      in monitoring anaesthesia and could be useful in adapting the peroperative
      administration of opioids. A range of information collected from the
      electroencephalogram, haemodynamic readings and pulse plethysmography might be
      necessary for monitoring the level of nociception during anaesthesia. Information
      theory, multimodal monitoring, and signal processing and integration are the
      basis of future monitoring.

PMID- 16634424
TI  - Use of cerebral monitoring during anaesthesia: effect on recovery profile.
AB  - This review article examines the effect of cerebral monitoring using an EEG-based
      device [i.e. bispectral index (BIS), patient state analyzer (PSA), auditory
      evoked potential (AEP), cerebral state index (CSI), or entropy] on titration of
      anaesthetic, analgesic and cardiovascular drugs during surgery. In addition,
      articles discussing the effects of these cerebral monitoring devices on recovery
      profiles following general anaesthesia, postoperative side effects, and
      anaesthetic costs are reviewed.

PMID- 16634425
TI  - Monitoring consciousness in intensive care medicine.
AB  - Sedation and analgesia are important components of care for critically ill
      patients. Avoiding over-as well as undersedation is of utmost importance as both
      states carry considerable risks and may influence outcome. The management of
      sedation has changed dramatically over the past two decades from providing a
      dosage level by which the patient was kept in a deep stage of anaesthesia to a
      current dosing strategy allowing the administration of drugs in line with
      individual need, resulting in most cases in a slightly sedated, cooperative
      patient. The importance of monitoring the level of sedation and analgesia has
      only recently been realised. Most importantly, regularly determining the
      appropriate level of sedation and analgesia as well as monitoring the desired
      level of sedation will help to minimise the adverse effects of sedation. Clinical
      sedation scales are, however, subjective, and most lack proper validation. Thus,
      an objective measure of sedation, such as the use of processed
      electroencephalogram (EEG) parameters is desirable. Processed EEG algorithms such
      as the bispectral index were initially introduced into clinical practice as a
      tool to assess the depth of anaesthesia objectively in the operating room.
      However, patients under general anaesthesia differ from those in an intensive
      care unit. Accordingly, most results from studies evaluating the performance of
      processed EEG parameters in critically ill patients have not been satisfactory.
      At present, monitoring sedation with processed EEG parameters cannot generally be
      recommended. However, in special situations such as deep sedation and
      neuromuscular blockade, in which clinical sedation scales are prone to failure,
      the bispectral index may help to assess the level of sedation.

PMID- 16634426
TI  - Monitoring consciousness in the pediatric patient: not just a small adult.
AB  - Intraoperative awareness, defined as postoperative memory for intraoperative
      events, is believed to occur about 0.2% of the time in a general adult surgical
      population. A recent large-scale prospective study from a single institution
      revealed a strikingly high incidence (0.8%) of intraoperative awareness in
      children aged 5-12 years although the sequelae of awareness during surgery in
      children were reported to be relatively minor. This contrasts with awareness in
      adult patients, for whom this complication often causes psychological trauma,
      thus having medico-legal implications. Various monitors to detect intraoperative
      awareness have been used with varying success in adults. To date, however, no
      monitor has been shown to be effective in detecting intraoperative awareness
      during surgery in pediatric patients. Further research is required to clarify the
      rates of intraoperative awareness in the pediatric population as well as the need
      for monitoring this event during the clinical practice of pediatric
      anesthesiology.

PMID- 16634427
TI  - Closed loops in anaesthesia.
AB  - Closed-loop systems are able to make their own decisions and to try to reach and
      maintain a preset target. As a result, they might help the anaesthetist to
      optimise the titration of drug administration without any overshoot, controlling
      physiological functions and guiding monitoring variables. Thanks to the
      development of fast computer technology and more reliable pharmacological effect
      measures, the study of automation in anaesthesia has regained popularity. This
      short review focuses on the most recently developed and tested feedback systems
      in anaesthesia. Various new approaches for controlling the administration of
      intravenous and inhaled hypnotic-anaesthetic drugs have recently been published.
      For analgesics, a framework for further research has been presented in the
      literature. For other drugs, such as muscle relaxants and haemodynamic agents,
      only short reviews can be found. Until now, most of these systems have had to be
      under development. The challenge is now fully to establish the safety, efficacy,
      reliability and utility of closed-loop anaesthesia so that it can be adopted in
      the clinical setting. Besides, their role in optimising the controlled variables
      and control models, these systems have to be tested in extreme circumstances in
      order to test their robustness.

PMID- 16634428
TI  - Processed EEG and patient outcome.
AB  - The era of research evaluating clinical outcomes associated with processed
      electroencephalogram (EEG) monitoring began with the first randomized trial of
      bispectral index monitoring (BIS) performed as part of the clearance process for
      approving routine clinical use of the BIS monitor by the United States Food and
      Drug Administration. Subsequent to this initial investigation, numerous other
      clinical investigations have demonstrated that the use of processed EEG monitors
      as an additional method of patient assessment and an aid to anaesthetic dosing
      can decrease anaesthetic usage and hasten recovery times. Because of the presumed
      association between anaesthetic effect and EEG changes, it is not surprising that
      the additional research has focused on the impact of processed EEG monitoring on
      postoperative outcomes and perioperative safety especially the prevention of
      intraoperative awareness.

PMID- 16634429
TI  - [Ultrastructural study of liver cells from rooks living in ecologically
      unfavorable areas].
AB  - The ultrastructure of liver cells was studied in rooks (Corvus frugilegus) living
      in radioactive and chemical contamination areas. The ultrastructure of liver
      cells from rook as well as jackdaw (Corvus monedula) and hooded crow (Corvus
      cornix) (Corvidae family) from a conventionally clean area was studied as
      control. Control hepatocytes proved to contain a great number of mitochondria,
      many of which were swollen and had clear matrix and disorganized cristae. The
      cristae nearly lacked glycogen and had abundant lipid droplets, which often
      tightly contacted mitochondria. The cytoplasm of hepatocytes in birds from both
      ecologically unfavorable areas had numerous mitochondria with the same
      ultrastructure. In contrast to control, the hepatocyte cytoplasm: (1) contained a
      lot of glycogen; (2) there were many lipid droplets, which directly contacted
      glycogen granules; and (3) had more abundant peroxisomes. In addition to normal
      erythrocytes, the sinusoids contained erythrocytes with mitochondria, vesicles,
      and lipid droplets in their cytoplasm. Analysis of many micrographs of lipid
      droplets contacting glycogen granules, mitochondria, peroxisomes, and cisterns of
      smooth endoplasmic reticulum allowed us to propose that glycogen is synthesized
      via gluconeogenesis from glycerol and products of fatty acid oxidation in the
      liver cell cytoplasm of rooks from ecologically unfavorable areas as distinct
      from control.

PMID- 16634430
TI  - [Molecular weight and subunit composition of GABA(A)-ergic compound-sensitive Cl
      , HCO3(-)-stimulated Mg2+ ATPase from the plasma membrane of carp brain (Cyprinus
      carpio L.)].
AB  - Molecular weight and subunit composition of Cl-, HCO3(-), and picrotoxin
      stimulated Mg(2+)-ATPase solubilized with sodium deoxycholate from the plasma
      membrane fraction of fish brain were studied by gel filtration. These enzymes
      were eluted from a Sephacryl S-300 column as a single peak and corresponded to a 
      300 kDa protein with a Stokes radius of 5.4 nm. The enzyme-enriched fraction
      concentrated and denatured by SDS was eluted from a Sephacryl S-200 column as a
      single subunit with a molecular weight of -56 kDa. SDS-PAGE also revealed a
      single major protein band with a molecular weight of -56 kDa. It was concluded
      that the molecular weight and subunit composition of CCl-, HCO3(-)-stimulated
      Mg(2+)-ATPase isolated from the plasma membrane of fish brain are similar to
      those of GABAA/benzodiazepine receptor complex from fish brain but differ from
      those of P-type transport ATPases.

PMID- 16634431
TI  - [Bacterioplankton of the Kola Bay, Barents Sea, (micro- and nanoforms) based on
      2002-2003 monitoring data].
AB  - Hydrochemical and microbiological investigation in the Kola Bay in 2002-2003
      demonstrated that the distribution of bacteria is notably influenced by
      biogeochemical barriers formed by mixing fresh and sea water. Seasonal changes in
      the appearance of filterable bacteria, considerable quantities of gram-positive
      bacteria with thick cell walls, dwarf bacteria, spheroplasts, elementary bodies,
      and cells with abnormal cell walls during the polar night have been revealed.
      Cultured bacterial colonies were represented by polymorphic cells. The data
      obtained refine our knowledge about organotrophic activity of bacterioplankton
      during the polar night.

PMID- 16634432
TI  - [Dynamics of the integral measure of competition in plant communities of
      different uniformity].
AB  - The effect of non-monotony of the correlation coefficient between crown
      projection area and the Voronoi polygon area in 90-year spruce sites in the
      Moscow Region arranged in ascending order of the variation coefficient of stem
      diameter is analyzed using the original 2D model of the plant community dynamics.
      Theoretical integral (over the entire community) indices of competition
      demonstrating non-monotone competition in relatively uniform communities--the
      Clements' index (Clements et al., 1929) and the mean suppression of community
      plants--were analyzed. Direct computation demonstrated that the correlation
      coefficient can also be considered as an index of competition, and its dynamics
      is indeed non-monotone in uniform communities. This finding allows us to roughly
      evaluate the potential duration of biomass growth for free-growing spruce in the
      Moscow Region as 1000 years. Due to the limitations of the 2D resource model
      (nearly "symmetric" competition), certain model characteristics of communities
      (the variation coefficient and correlation characteristics of neighborhood)
      differed several times from natural ones although showing the correct trend of
      changes.

PMID- 16634433
TI  - [Phylogenetic reconstruction of weevil superfamily Curculionoidea (Coleoptera)
      using the SYNAP method].
AB  - Phylogenetic relationships within the superfamily Curculionoidea were
      reconstructed. Autapomorphies of the superfamily Curculionoidea include more or
      less pronounced snout, clubbed antennae, and partially sclerotized or completely
      membranous male tergite 9. Weevil families can be divided into three groups. The
      first group includes the most primitive family Nemonychidae. The second group
      includes nine families (Anthribidae, Belidae, Oxycorynidae, Eccoptarthridae,
      Allocorynidae, Rhynchitidae, Attelabidae, Ithyceridae, and Brentidae). The third
      ("higher") group includes six families (Brachyceridae. Cryptolaryngidae,
      Dryophthoridae, Curculionidae, Scolytidae, and Platypodidae).

PMID- 16634434
TI  - [Taxonomic relations between forms in evolutionary young complexes of
      lepidopterans (Insecta, Lepidoptera)].
AB  - Morphological characteristics of the prototype wing pattern can be used in
      lepidopteran population studies as markers of population groups and
      interpopulation boundaries. The centers of phenotypic variation serving as
      speciation centers were recognized within the range of polytypic species.
      Revision of the polytypic complex Polyommatus icarus Rott. allowed us to
      recognize six specific and six subspecific taxa.

PMID- 16634435
TI  - [Sexual dimorphism of marbled polecat Vormela peregusna (Carnivora: Mustelidae)].
AB  - Analysis of morphometric variation in 26 cranial characters were studied in 85
      individuals of marbled polecat Vormela peregusna from Turkmenistan demonstrated a
      low level of sexual dimorphism in the species. The properties of sexual
      dimorphism in marbled polecat are discussed in terms of available hypotheses of
      sexual dimorphism in carnivores.

PMID- 16634436
TI  - [Comparative analysis of growth of edible mussel Mytilus edulis from different
      White Sea regions].
AB  - Growth properties were studied in edible mussel Mytilus edulis from different
      biotopes of the Kandalaksha Bay in the White Sea. Growth curves of the mussel
      shell were approximated by the von Bertalanffy equation. The highest growth rate,
      primarily dependent on hydrological conditions, was observed in mussels from the
      Chupa Bay (Levin Navolok fishery), while the lowest rate was observed in mussels
      from the Umba region (Turn Cape, Murmansk Region). Allometric relationships of
      the mussel shell were determined. Analysis of the relationship between the
      maximum width/convexity and their length demonstrated that this relationship is
      described by a single allometric equation for mussels from the Umba region, which
      indicates the homogeneity of this population. For mussels from the Chupa Bay,
      this relationship cannot be described by a single equation, which points to the
      population heterogeneity. For 90% mussels from this region, the shell
      width/convexity ratio ranged from 0.5 to 0.9; while for the remaining 10%, it
      ranged from 0.9 to 1.15.

PMID- 16634437
TI  - [Comparison of anticoagulant effects of regulatory proline-containing
      oligopeptides. Specificity of glyprolines, semax, and selank and potential of
      their practical application].
AB  - Experimental and theoretical demonstration of different effect of certain
      regulatory peptides (RPs) on blood coagulation is available. The problem of the
      role of RPs in hemostatic processes becomes particularly significant since,
      first, the peptides are widespread in nature both in animal and plant tissues,
      second, there is a relationship between the peptide structure and function and,
      third, both natural and synthetic peptides are used in practical medicine to
      correct functions of some factors of the hemostatic system. Many peptide
      inhibitors of the primary and plasma hemostasis potentiating anticoagulant
      effects in the body have been described.

PMID- 16634438
TI  - [Study of the relationship between analgesic activity and structure of synthetic
      melanocortin analogs].
AB  - Melanocortins, peptides of the family of adrenocorticotropic (ACTH) and
      melanocyte-stimulating (MSH) hormones, have a wide range of physiological
      activity. Heptapeptide semax (MEHFPGP) is an analog of the ACTH4-10 fragment.
      Previously, pronounced nootropic and neuroprotective activities were shown for
      this peptide; in addition, it decreases pain sensitivity in animals. In this
      work, the relationship between analgesic activity of the peptide and its
      structure was studied. The following analogs of the N-terminal ACTH fragments
      were used: rMEHFPGP, where r is glucuronic acid, KEHFPGP, GEHFPGP, EHFPGP, HFPGP,
      and ERP. The peptides were administered intraperitoneally at doses of 0.015, 0.05
      and 0.5 mg/kg. Rat pain sensitivity was assessed using the paw-withdrawal test.
      Truncations of the N-terminal residues eliminated the analgesic activity. The
      peptide analgesic effect was observed after the replacement of the N-terminal
      methionine with lysine or after the attachment of glucuronic acid to the
      methionine, while the peptide with glycine instead of the methionine had no
      effect on pain sensitivity. Hence, the amino acid at position 1 of semax analogs
      plays a key role in mediating the analgesic effects of the peptides.

PMID- 16634439
TI  - [Effect of nitrite-induced methemoglobinemia on the kinetics of blood
      deoxygenation].
AB  - Kinetics of blood deoxygenation was studied during acute hypoxia induced by
      subcutaneous administration of sodium nitrite using polarographic method. Plasma
      oxygen tension remained unaltered as the dose of sodium nitrite increased, while
      the dynamics of oxygen release was dose-dependent. The constant of oxyhemoglobin
      deoxygenation rate proved to vary with blood deoxygenation. The nitrite-induced
      deceleration of oxyhemoglobin deoxygenation was due to the inactivation of a
      fraction of hemoglobin as well as to the increased hemoglobin oxygen affinity and
      possible changes in the oxygen permeability of erythrocyte membranes during acute
      methemoglobinemia.

PMID- 16634440
TI  - [Species composition and distribution of foraminifers in the Deryugin Basin (Sea
      of Okhotsk)].
AB  - Analysis of the composition and quantitative distribution of foraminifers in
      bathyal sediments collected at 14 stations in the Deryugin Basin and at 11
      stations in other regions of the Sea of Okhotsk, Sea of Japan, and North Pacific
      demonstrated specific foraminifer complex in the basin at depths from 1650 to
      1800 m associated with cold barite/methane seeps. Oligomixed biocenosis with
      prevailing agglutinated foraminifers and Saccorhiza ramosa as the dominant was
      shown to develop in these zones.

PMID- 16634441
TI  - [Impact of chemical weapon destruction on the structure of lake zoohydrobiont
      community].
AB  - Community structure of zoohydrobionts in the lake affected by chemical weapon
      destruction was studied for the first time. Low pH favored species specific to
      acidic water bodies as well as bidominant zooplankton community. The long-term
      effects of chemical pollution determined the stage of community succession,
      namely, the absence of the key predator (fishes), abundance of detritus consumers
      in the zoobenthic community (dipteran larvae), diversity of amphibiotic insects,
      and low species diversity in the zooplankton community with the prevalence of
      cladocerans and rotifers. Unbalanced composition of higher trophic levels results
      in an unstable functioning of the lake and accumulation of significant amounts of
      detritus, which is utilized by the abundant microzoobenthic component of the
      ecosystem.

PMID- 16634442
TI  - [Cytogenetic responses of birch to stress factors].
AB  - The following range of changes in response to anthropogenic stress has been
      revealed in experimental birch seedlings relative to control: increased mitotic
      index, the range and frequency of abnormal mitoses, number of cells with
      persistent nucleoli, and number of cells in prophase. Cells with vacuolated
      cytoplasm were also observed. The mutagenic pressure on the organisms in the
      industrial areas of Voronezh demonstrated a trend to increase, which points to
      their high environmental pollution.

PMID- 16634443
TI  - [Microbial transformation of chitin in soil under anaerobic conditions].
AB  - Anaerobic chitinolytic complex was studied in three soil types: chernozem, gray
      forest soil, and chestnut soil. The abundance and biomass of anaerobic
      chitinolytic microbial complex of fungi, bacteria, and actinomycetes were
      evaluated by luminescent microscopy. The dynamics of methane emission from soil
      during chitinolytic succession was studied by gas chromatography. All three
      studied microbial groups proved to participate in chitin transformation in soil
      under anaerobic conditions. The highest biomass growth was observed among
      prokaryotes, particularly actinomycetes, whose biomass doubled. The increase in
      methane emission during chitinolytic succession was most pronounced in soils with
      low organic matter content.

PMID- 16634444
TI  - [Some patterns of age and geographical variation in fish fecundity].
AB  - Some patterns of age and geographical variation in fecundity indices were
      analyzed in three freshwater fishes (river perch, bream, and Sevan khramulya). A
      trend to increase in the ovarian relative weight and mature egg size with age has
      been revealed. Two species with a wide range (perch and bream) demonstrated a
      tendency to decrease in the ovarian relative weight and increase in the
      definitive oocyte weight in females of populations living in the geographical
      center of the range. The coefficient of correlation between the absolute
      individual fecundity and body weight of females was proposed as a population
      marker of the fish reproductive system.

PMID- 16634445
TI  - [Impact of coal mining on bird distribution in Upper Angara Region].
AB  - Bird distribution in the first half of summer was analyzed in the areas of past
      and present opencast coal mining in the Upper Angara Region. Most species
      preferred forest habitats even with traces of industrial impact. Artificial water
      bodies introduced as a result of coal mining increase the diversity of bird
      species.

PMID- 16634446
TI  - End-of-life care a balance between customization, standard processes.
AB  - Regularly revisit patient goals as the patient's condition changes. Total
      elimination of pain is a legitimate quality issue. More palliative care is needed
      in the hospital setting, experts say.

PMID- 16634447
TI  - Computer system helps nurses in care delivery.
AB  - Sign-out module is incorporated into hospital's electronic medical record. Fields
      populated with patient demographic and admit-discharge-transfer data; medical
      team information; allergies; active medication lists; and resuscitation status.
      Boost in nursing morale an unexpected benefit of the new system.

PMID- 16634448
TI  - Program helps to boost co-pay collections.
AB  - Co-pays, when required, are collected at bedside during a visit by a facilitator.
      Patient phone surveys address staff care and compassion, responsiveness,
      communication, friendliness, and courtesy. Staff who meet pre-stated goals can
      increase compensation by as much as 6%.

PMID- 16634449
TI  - Study: quality improving at a modest pace.
AB  - Study shows 10.2% improvements in patient safety core measures. Worst performer
      among 44 core measures was ED patients who left without being treated. Hospital
      procedures generally performed better than prevention in chronic disease states.

PMID- 16634450
TI  - Usage of CPOE steadily increasing, leapfrog says.
AB  - By the end of 2006, about 10% of all hospitals will have completed CPOE
      implementation. Few statistically significant organizational factors were
      correlated to the variability in CPOE implementation. P4P will help
      implementation rate, but high cost of systems will remain a barrier.

PMID- 16634451
TI  - CDC issues updated TB prevention guidelines.

PMID- 16634452
TI  - [Current issues in neurourology].
AB  - The author gives an overview on the pathophysiology and management of neurogenic
      bladder dysfunction and lists the most common bladder dysfunctions observed in
      various diseases of the nervous system. The cited classifications, principles,
      and categories follow the current guidelines of WHO and the International
      Continence Society. The author and his co-workers have been involved in the
      rehabilitational treatment of patients with neurogenic bladder dysfunction for
      more than a decade. The review paper is supplemented with illustrations taken
      from the author's own cases.

PMID- 16634453
TI  - Plasticity of nociception: recent advances in function-oriented structural pain
      research.
AB  - Traditional concept holds that the pain unit consists of three neurons. The first
      of these, the primary nociceptive neuron, starts with the nociceptors and
      terminates in the dorsal spinal cord. The second one, called spinothalamic
      neuron, crosses over in front of the central canal and connects the dorsal horn
      with the thalamus. The third one, called thalamo-cortical neuron, terminates in
      the "pain centres" of the cerebral cortex. While this simplistic scheme is useful
      for didactic purposes, the actual situation is more complex. First, in the
      periphery it is only nociception that occurs, while pain is restricted to the
      levels of thalamus and the cortex. Second, pain results from interactions of
      excitation and inhibition, from divergence and convergence and from attention and
      distraction, in a diffuse and plastic system, characteristic for all levels of
      organization. This study describes the major cytochemical markers of primary
      nociceptive neurons followed by the presentation of recent data on the functional
      anatomy of nociception and pain, with special focus on the intrinsic
      antinociceptive system and the role of nitrogen oxide, opiate receptors,
      nociceptin and nocistatin. In addition to the classic intrinsic antinociceptive
      centres such as the periaqueductal gray matter and the raphe nuclei, roles of
      several recently discovered members of the antinociceptive system are discussed,
      such as the pretectal nucleus, the reticular formation, the nucleus accumbens,
      the nucleus tractus solitarii, the amygdala and the reticular thalamic nucleus,
      this latter being a coincidence detector and a centre for attention and
      distraction. The localisation of cortical centres involved in the generation of
      pain are presented based on the results of studies using imaging techniques, and
      the structural basis of corticospinal modulation is also outlined. Seven levels
      of nociception and pain are highlighted where pharmacological intervention may be
      successful, 1. the peripheral nociceptor, 2. the spinal ganglion, 3. the
      multisynaptic system of the dorsal horn, 4. the modulatory system of the brain
      stem, 5. the antinociceptive system, 6. the multisynaptic system of the thalamus,
      and 7. the cortical evaluating and localisation system that is also responsible
      for descending (inhibiting) control. The many levels of nociception and pain
      opens new ways both for pharmacological research and the general practitioner
      aiming to alleviate pain.

PMID- 16634454
TI  - [The use of intravenous immunglobulin in the treatment of autoimmune
      neuromuscular diseases].
AB  - Intravenous immunglobulin given in autoimmune neuromuscular disorders modulates
      the immune system by complex actions, including, 1. the modification of the
      expression and function of Fc receptors, 2. interference with the activation of
      the complement and the cytokine network, 3. neutralisation of antiidiotypic
      antibodies, 4. effects on the activation, differentiation and effector functions
      of the T and B cells. Controlled trials have shown that intravenous immunglobulin
      is effective as first-line therapy in patients with Guillain-Barre syndrome and
      multifocal motor neuropathy. In case of steroid resistance or coexisting diabetes
      mellitus, intravenous immunglobulin can be the first line therapy in chronic
      inflammatory demyelinating polyneuropathy as well. As an alternative therapy it
      can be a second-line choice in dermatomyositis, myasthenia gravis, Lambert-Eaton
      myasthenic syndrome, and stiff person syndrome. While it has a remarkably good
      safety record for long-term administration the following side effects have been
      observed: headache, skin rash, thromboembolic events and renal tubular necrosis.
      In some disorders, the appropriate dose and frequency of infusions that maintain
      a satisfactory therapeutic response is well defined on the basis of data of
      evidence-based medicine, whereas in others it still remains to be defined. For
      the analysis of pharmacoeconomical aspects and the mechanism(s) of response
      differences in the same disease categories, further studies are necessary.

PMID- 16634455
TI  - [Interactions between the MTHFR C677T and MTHFR A1298C mutations in ischaemic
      stroke].
AB  - INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C
      mutations, being considered unfavourable genetic factors by causing elevated
      serum homocysteine levels, may be risk factors for cardiovascular disorders,
      including ischaemic stroke. In this study, the role of these two mutations in
      ischaemic stroke was examined: PATIENTS AND METHODS: Genetic and clinical data
      were analysed of 122 ischaemic stroke patients and 102 control subjects with no
      lesions by neuroimaging. RESULTS: Neither of the two MTHFR mutations alone was
      found to be a significant genetic risk factor for ischaemic stroke. However, at
      least one MTHFR 677T allele combined with at least one MTHFR 1298C allele
      significantly increased the risk of ischaemic stroke (adjusted odds ratio: 3.39;
      p < 0.001). CONCLUSION: The synergistic effect between the two MTHFR mutations
      may represent a new genetic stoke risk factor.

PMID- 16634456
TI  - [Ultrasonographic expressions of the fetal face may reflect fetal mood--mimicry
      is part of fetal ethology].
AB  - The author studied foetal faces and changes in features in the coronal plane
      during routine prenatal ultrasound scans. Based on known behaviour of children
      and adults, deductions can be made about foetal mood alterations. During the four
      years of the study the author noted five main facial expression changes that
      might be reflections of foetal mood. Foetal expressions and fine lineaments may
      indicate adequate maturity of the central nervous system as well as satisfactory
      oxygen supply. Ethologically, facial mimicry is an inherited behavioural pattern.

PMID- 16634457
TI  - [Spectral EEG-characteristics of subcortical ischemic brain lesion--a case
      study].
AB  - INTRODUCTION: Although the EEG-changes caused by ischemic stroke are well known,
      data of the literature are rather ambiguous. The EEG-findings recorded in a
      patient with a unilateral subcortical ischemic lesion are evaluated with special
      emphasis related to the effect of the dynamics caused by eye opening.
      PARTICIPANTS AND METHODS: Data recorded from a patient (54 years old male with a
      completed stroke involving the frontal and parietal subcortical region in the
      left side) were compared to those of a control group (12 healthy age matched
      subjects). Absolute and relative frequency spectra, theta/beta quotients, the
      interaction index characterizing the effect of eyes opening and the symmetry
      index were calculated from the EEG recorded in eyes closed and eyes open
      conditions. Data of the patient were compared to those recorded in the control
      group on the basis of 95% confidence intervals. RESULTS: Irrespective of the
      recording conditions the predominance of slow activity and the increase of
      theta/beta quotients were found in the absolute frequency spectra. The increase
      of beta and beta2 frequency bands following eye opening on the side of the lesion
      were found to be less obvious than that seen on the intact side and that observed
      in the control group. With respect to the interaction index related to the side
      differences caused by eye opening the change of the beta2 frequency band was
      found to be the most conspicuouS. The symmetry index underscored the predominance
      of slow (delta, theta, alpha1) frequencies on the lesion side, and that of the
      fast (beta1, beta2) frequencies on the intact side in both recording conditions.
      CONCLUSIONS: Localized lesion of the white matter without cortical damage can
      cause the predominance of slow activity and decrease of the fast frequency bands
      on the side of the lesion which can be shown by the absolute frequency spectra
      and is revealed by the symmetry index. The lack of functional reactivity of the
      fast frequencies in the side of the lesion can clearly be seen in the change of
      relative spectra following eye opening and on the basis of the calculation of the
      interaction index reflecting the dynamics of side differences.

PMID- 16634458
TI  - [Drug problems, psychopathology in youth, factors of sociocultural background].

PMID- 16634459
TI  - Functional consequences of basal ganglia pathologies.

PMID- 16634460
TI  - [Reply on the vascular tunnel issue by right of the last word].

PMID- 16634461
TI  - Linking dementia research to policy: an example using fluorodeoxyglucose positron
      emission tomography for the diagnosis of Alzheimer's dementia and mild cognitive
      impairment.

PMID- 16634462
TI  - Treating Alzheimer's disease: do clinical trial methods produce unnecessary
      practitioner dilemmas?
AB  - Recent clinical trials and critical reviews of Alzheimer's disease (AD) research
      discourage already relatively sparing clinical uses of cholinesterase inhibitors
      (ChEIs) considering the prevalence of AD. As evidence against use of this class
      of drugs, detractors cite critical reviews of ChEIs and lack of long-term health
      benefits found in one long-term clinical trial. This paper describes the use of
      standard error of measurement to allow investigators to design clinical trials
      that address these issues. The new clinical trial procedures afford sufficient
      precision for two purposes. First, practitioners can assess individual patients
      with precision and certainty in their observations. Second, clinical trial
      researchers can study how short-term drug effects on individual patients predict
      long-term benefits from continued treatment. With these more clinically
      informative clinical trial designs, investigators would be able to avoid
      uncertainties currently raised by conflicts between short- and long-term AD
      clinical trials.

PMID- 16634463
TI  - Caregivers' perceptions of dementia patients' functional ability.
AB  - Dementia patients' caregivers often provide information about patients' daily
      functioning, but little is known about factors influencing caregivers'
      perceptions. Baseline data from an intervention trial were used to compare
      caregiver estimates of dementia patients' performance with their actual
      performance of instrumental activities of daily living (IADLs) and to assess
      relationships between measures of caregiver responses to caregiving, self
      perceived sense of self-efficacy, and depression. We also assessed patient
      cognition, overall function and behavioral disturbance, and caregivers'
      perceptions of their patients' behavior as manipulative or deliberate.
      Disparities between these estimates and actual patient performance on structured
      IADL tasks were unrelated to any caregiver, patient, or relationship factor that
      we measured

PMID- 16634464
TI  - Apolipoprotein epsilon-4 allele and the two-year progression of cognitive
      function in Chinese subjects with late-onset Alzheimer's disease.
AB  - BACKGROUND: Although the significance of apolipoprotein E4 (Apo E4) in
      Alzheimer's disease (AD) has been well established in Caucasian populations, its
      role in determining the rate of cognitive decline in other ethnic groups has yet
      to be determined. This study examined the two-year progression of cognitive
      decline and its association with Apo E4 allelic status in a group of Chinese
      elderly subjects with AD. METHOD: One hundred and four Chinese subjects with mild
      and moderate AD as assessed by the Clinical Dementia Rating (CDR 1 and 2) were
      followed up at a mean (SD) duration of 22.53 (5.21) months. The rate of cognitive
      decline and its association with Apo E4 allelic status was evaluated RESULTS: At
      follow-up, 74 (73 percent) subjects were reassessed. Forty-nine remained stable
      at the same CDR and 25 had deteriorated. The mean (SD) deterioration in the Mini
      Mental State Examination (MMSE) was 2.52 (4.38) and in the Mattis Dementia Rating
      Scale (DRS) was 9.03 (14.98) (paired t-test, p < 0. 001). There was no
      significant difference in the baseline MMSE and DRS scores between the "stable",
      "deteriorated", or "deceased" groups. Mildly demented subjects with the Apo E4
      allele were more likely to have deteriorated to a more severe CDR than subjects
      without the Apo E4 allele (Pearson chi2 = 5.72, df 1, p = 0.017, Odds ratio =
      6.3, CI 1.3 to 30.53). CONCLUSION: The presence of the Apo E4 allele may
      influence the rate of cognitive deterioration, particularly in subjects with mild
      AD.

PMID- 16634465
TI  - Management of aggression, agitation, and psychosis in dementia: focus on atypical
      antipsychotics.
AB  - The behavioral and psychological symptoms of dementia (BPSD), such as psychosis,
      agitation, or aggression have a considerable negative impact on the quality of
      life of both patients and their caregivers. Multiple studies have demonstrated
      that atypical antipsychotics are efficacious in the treatment of the aggressive
      and psychotic symptom clusters, and here we review their use in this indication.
      Because of the safety concerns associated with the use of atypical antipsychotics
      in this population, these drugs must be used judiciously. For patients with
      severe BPSD such as psychosis, agitation, or aggression, for whom there are few
      options, atypical antipsychotics, particularly risperidone and olanzapine, should
      be considered.

PMID- 16634466
TI  - Challenges in the clinical diagnosis of Alzheimer's disease: influence of "family
      coaching" on the mini-mental state examination.
AB  - The Mini-Mental State Examination (MMSE) is a commonly used clinical tool for
      evaluating the cognitive aspects of mental function. In this study, 40
      consecutive patients presenting to a memory disorder clinic and their caregivers
      were evaluated for coaching of the patient with respect to MMSE content over the
      24 hours prior to clinical evaluation. Caregivers completed a questionnaire
      concerning MMSE practice sessions with the patient prior to the physician
      encounter; then, the patients were asked to spell the word "WORM" backwards
      instead of "WORLD" during the MMSE test. Some or all of the MMSE content was
      reviewed with the patient prior to the interview by 42.5 percent of the
      caregivers; 17.5 percent of patients spelled or attempted to spell "WORLD"
      backwards instead of "WORM". These results demonstrate that coaching of patients
      prior to administration of the MMSE is not uncommon, and that this needs to be
      taken into consideration when forming therapeutic decisions based on MMSE
      results.

PMID- 16634467
TI  - Herbal medicine in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by profound memory loss sufficient to
      interfere with social and occupational functioning. It is the most common form of
      dementia, affecting more than 20 million people worldwide. AD is characterized by
      an insidious loss of memory, associated functional decline, and behavioral
      disturbances. Patients may live for more than a decade after they are diagnosed
      with AD, making it the leading cause of disability in the elderly. The incidence
      of AD ranges from 1 to 4 percent of the population per year, rising from its
      lowest level at ages 65 to 70 years to rates that may approach 6 percent for
      those over the age of 85 years. The first neurotransmitter defect discovered in
      AD involved acetylcholine (ACh). As cholinergic function is required for short
      term memory, the cholinergic deficit in AD was also believed to be responsible
      for much of the short-term memory deficit. Clinical drug trials in patients with
      AD have focused on drugs that augment levels of ACh in the brain to compensate
      for the loss of cholinergic function. These drugs have included ACh precursors,
      muscarinic agonists, nicotinic agonists, and acetylcholinesterase inhibitors. The
      most highly developed and successful approaches to date have employed
      acetylcholinestrase inhibition. Although some Food and Drug Administration
      approved drugs are available for the treatment of Alzheimer's disease, the
      outcomes are often unsatisfactory, and there is a place for alternative medicine,
      in particular, herbal medicine. This paper reviews the clinical effects of a
      number of commonly used types of herbal medicines for the treatment of AD.

PMID- 16634468
TI  - Recognition and treatment of Alzheimer's disease: a case-based review.
AB  - Early recognition and treatment initiation are pivotal in managing Alzheimer's
      disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and
      should include treatment initiation with cholinesterase inhibitors (ChEIs) to
      improve cognition, management of comorbid conditions, and treat behavioral
      symptoms. Caregiver compliance is integral to AD treatment success. The purpose
      of this report is to present two real case studies of "suspected" AD or related
      dementia and stress the significance of early and accurate diagnosis in disease
      management. In case 1, a caregiver reports gradual but progressive loss of
      memory, and the patient himself complains of memory impairment. Neuroimaging
      analysis confirms "typical " AD. In case 2, initiation of ChEI therapy is
      followed by substantial clinical improvement in the face of a complex medical
      picture, and neuroimaging revealing more neurodegenerative changes than could be
      accounted for by "pure" AD.

PMID- 16634469
TI  - Antioxidant protection and neurodegenerative disease: the role of amyloid-beta
      and tau.
AB  - In Alzheimer's disease (AD), the major components of senile plaques and
      neurofibrillary tangles, amyloid-beta and tau, respectively, are thought by many
      to play a key role in disease initiation and progression. However, herein we
      propose that rather than being initiators of disease pathogenesis, the lesions
      that characterize AD, senile plaques and neurofibrillary pathology, occur
      consequent to oxidative stress and, importantly, function as a primary line of
      antioxidant defense. Importantly, this paradigm shift in thinking about the role
      of lesions in disease also provides an explanation for the appearance of both
      amyloid-beta and tau in control individuals given the increased levels of
      oxidative stress associated with the aged brain. In AD, oxidative stress is not
      only high but chronic and is superimposed upon an age-related vulnerable
      environment. Therefore, one would predict, successfully, an increased lesion load
      in patients with AD above and beyond that seen in normal aging. The notion that
      amyloid-beta and tau accumulations indicate adaptation and, likely, physiological
      processes sheds light on the pathological expression of disease and calls into
      question the rationale of current therapeutic efforts targeted toward lesion
      removal.

PMID- 16634470
TI  - Family history of dementia does not influence the progression of Alzheimer's
      disease at two years: results from the REAL.FR Study.
AB  - The purpose of this study was to determine whether a family history of dementia
      in a first-degree relative influenced the progression of Alzheimer's disease (AD)
      after two years of follow-up. Patients were recruited in the REAL.FR (Reseau sur
      la Maladie d'Alzheimer Francais) study and underwent behavioral, global,
      nutritional, and medical evaluation with assessment of cognitive function and
      independence every six months. At inclusion, 113 patients reported a family
      history of dementia, and 358 patients had no family history of dementia. There
      was no statistical difference for any factors between the two groups at baseline.
      After two years of follow-up, a similar percentage of patients were still
      followed in each group, and although most parameters showed significant
      deterioration, there was no difference between the two groups, indicating that a
      family history of dementia does not appear to influence the progression of AD.

PMID- 16634471
TI  - [Role and future of public health in the European context].
AB  - Article presents the necessity of systematic enhancement of Public Health in the
      Czech Republic. Theoretical outlines of the basic development of medicine and
      health care are given, definition of Public Health and thesis of the EUPHA
      document (European Public Health Association) which concern developmental
      priorities of Public Health in Europe are presented.

PMID- 16634472
TI  - [Brain diseases and modern-day society].
AB  - Brain diseases represent one of the largest strains in the developed societies of
      the modem world. The major lost is in the indirect expenses caused by psychical
      disorders. Psychiatric diseases start frequently in childhood, affect from the
      life lasting view one half of the population and frequently result in
      disablement. Administrative of the World Health Organization and of European
      Union consider these problems highly important and require emancipation of
      psychically disabled, including the financial support for the care. Only 4% of
      the National Budget is directed to that sector in Czech Republic, which is the
      second lowest share (after Slovakia).

PMID- 16634473
TI  - [Paranoid syndrome, paranoid reaction, paranoia].
AB  - The term paranoid is derived from the Greek word paranoia meaning nadnese. It
      does not only mean self-reference, but there are various personality features as
      they are hostility, a tendency towards aggressiveness, irritability, a lack of
      sense of humour, feelings of overestimation of one-self and a tendency towards
      accusations. These features may appear also within normal psychology and they
      becomeclinically important after thein increase of intensity and conspicuousness
      (los sof hearing, long-term abuse of alcohol and psychostimulants) and organic
      disorders of the brain may contribute to the development of paranoidity. A
      mechanism of projection is considered as a decivise factor from the point of view
      of dynamic psychiatry. Clinically unimportant sign sof paranoidity can be
      observed due to unusual situations. If a paranoid reaction becomes more serious,
      formation of a paranoid delusion should be taken to account. In our koncept the
      term paranoid and paranoidity should be used only as a psychopathological term.

PMID- 16634474
TI  - [New questions and their solution in eating disorders].
AB  - Eating disorders represent a continuum in the pathological feeding behaviour with
      anorexia and severe malnutrition as one extreme and with psychogenic overeating
      and atypical forms of Eating disorders accompanied with obesity as the second
      extreme. World-wide epidemical spread of obesity and consequences of obesity
      frequently results in neglection of eating disorders problems and in apprehension
      of obesitologists that the Eating disorders prevention could challenge their
      efforts in the prevention of obesity. Because the scientific approach can enrich
      both fields, possibilities to improve cooperation between them in the fields of
      clinical and preventive care are studied. They are based on the recognition of
      common risk factors and in the more effective and aimed prevention and therapy.
      Some new discoveries in this field are discussed.

PMID- 16634475
TI  - [Photodynamic therapy used in dermatology--futher method development].
AB  - Dermatological use of photodynamic therapy and photodynamic diagnostics is
      reviewed in this paper. Principle, practice, photosensitisers, indications and
      side effects are described.

PMID- 16634476
TI  - [Contemporary alternatives in the diagnostics and therapy of female androgenetic
      alopecia].
AB  - Female androgenetic alopecia belongs to the family of scar-less, diffuse,
      telogenic, hormonally determined alopecias with hereditary disposition. In the
      androgenetic alopecia, progressive, androgen mediated miniaturization of
      genetically predestined hair follicles develops. Genetic factors play a role
      namely in females without the higher serum androgen level. Pathologically high
      level of serum androgens is usually accompanied with signs of virilization. Hair
      dropping starts in the fourth decade or earlier. It occurs in the postmenopausal
      period, after a pregnancy, after the onset or termination of peroral
      contraception, in women treated by aromatase inhibitors.

PMID- 16634477
TI  - [Planned laparoscopic procedures in clinical practice].
AB  - Several recent randomized studies have proved that laparoscopic technique is
      feasible, safe and has been associated with better cosmetics, less pain, faster
      recovery, lower incidence of infectious complications, and shorter postoperative
      stay. However, these advantages are not substantial for patients with malignant
      diseases. New published randomized trials (laparoscopic gastrectomy, colectomy,
      nephrectomy) have proved that long-term survival data did not show any
      detrimental effect of laparoscopy in comparison with historic studies of open
      resections.

PMID- 16634478
TI  - [Mutations in tumor suppressor gene NBS1 in adult patients with malignancies].
AB  - BACKGROUND: Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS I
      are found in 1% Slavic populations. Increased occurrence of cancer was repeatedly
      reported in adult relatives of patients with Nijmegen breakage syndrome. Among
      children with oncological problematic, nonsignificantly increased frequency of
      NBS1 heterozygotes was found, which seems not to play any important role in
      cancerogenesis in childhood. However, the proportion of NBS heterozygotes among
      adult patients with malignancies could be significant and their therapy and
      follow up should respect their hyperradiosensitivity. METHODS AND RESULTS:
      Mutations in exon were studied in 706 adult patients with malignancies. We found
      5 NBS heterozygotes, which not more than the population prevalence (1:129-165).
      Increased frequency of NBS heterozygotes was found among patients with colon and
      rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98).
      CONCLUSIONS: Surprisingly only one NBS heterozygote was found among 228 patients
      with nonHodgkin lymphoma, the malignancy which is a common complication in NBS
      homozygotes. Other types of malignancies were uncommon and only one R215W
      heterozygote was found. Comparison frequency of NBS heterozygotes with incidence
      NBS among person older than 70 years shows significant difference. Prevention of
      malignancies by avoidance from ionisation could be realized also in relatives of
      patients after identification of their genotype.

PMID- 16634479
TI  - [Development of incidence of post-dural puncture headache in patients undergoing
      caesarean section in spinal anaesthesia at the Department of Obstetrics and
      Gynecology in Olomouc during 2003-2004].
AB  - BACKGROUND: Paper gives the analyse of the incidence of post-dural puncture
      headache in patients undergoing caesarean section in spinal anaesthesia at the
      Department of Obstetrics and Gynecology in Olomouc in 2003-2004. METHODS AND
      RESULTS: Post-dural puncture headache following caesarean section in spinal
      anaesthesia in 2003 was retrospectively analysed. Subsequently, measures to
      reduce the incidence of this complication (use of Whitacre and Atra ucan needles)
      were implemented. 2004 patients were followed prospectively. 54 caesarean
      sections - 16.3% (54/331) were performed in spinal anaesthesia in 2003. Following
      needles were used to establish spinal blockade: Quincke 22G - 35.2% (19/54),
      Quincke 25G - 50% (27/54), Atraucan 26G - 14.8% (8/54). Post-dural puncture
      headache occurred in 9 cases - 16.6% (9/54) (22G - 7x, 25G - 2x), the onset of
      symptoms occurred after 24 to 65 hours after the spinal blockade (mean 41.7). It
      was necessary to perform epidural blood patch (EBP) in 7 cases - 77% (7/9) -
      12.9% (7/54) (22G - 5x, 25G - 2x). Epidural blood patch (EBP) was performed after
      7 to 45 hours after the onset of symptoms (median 28.4). The age of patients at
      the time of delivery ranged between 22 to 43 years (median 34.5). 36 caesarean
      sections - 8.4% (36/426) were performed in spinal anaesthesia in 2004. Following
      needles were used to establish spinal blockade: Whitacre 27G - 63,9% (23/36),
      Atraucan 26G - 13,9% (5/3), Quincke 25G - 11,1 (4/36), Quincke 22G - 11,1%
      (4/36). Post-dural puncture headache (PDPH) occurred in 3 cases - 8.3 (3/36) (25G
      - 1x, 22G - 2x), the onset of symptoms occurred after 24 to 54 hours after spinal
      blockade (median 36.0). It was not necessary to perform epidural blood patch. The
      age of patients at the time of delivery ranged between 22 to 39 years (median
      28.5). CONCLUSIONS: Incidence of post-dural puncture headache (PDPH) is
      significantly higher in pregnant women and in puerperal period compared to
      general population. The use of appropriate needles for spinal blockade and
      adequate level of anaesthesiologist's skills lead to lower incidence of post
      dural puncture headache (PDPH) after caesarean section performed in spinal
      anaesthesia.

PMID- 16634480
TI  - [Chronic post-mastectomy pain].
AB  - BACKGROUND: Surgery results in chronic pain in 7-80 percent. One of the most
      studied is chronic post-mastectomy pain. The prevalence was 40-50 percent in
      studies performed abroad. As this problem has not yet been studied in the Czech
      Republic, a retrospective prevalence study was performed to asses the extent of
      the problem and risk factors for development of chronic post-mastectomy pain.
      METHODS AND RESULTS: After ethic committee approval an anonymous questionnaire
      was developed and distributed in various oncology department and
      patients'organisations. Response rate was 100 percent, 330 questionnaires were
      processed. Chronic post-mastectomy pain (lasting longer than 3 months after
      surgery) was described by 69 (20.9 per cent) women. The pain was permanent in 17
      and transient in 46 cases, not specified in 6 cases. The pain intensity was
      predominantly mild or moderate. Risk factors were younger age (below 55-60 years,
      p=0.0098), less extensive surgery (tumourectomy vs. mastectomy, p=0.0017),
      intensive post operative pain (p=0.0002) and radiotherapy (p=0.0174). Trend in
      chemotherapy (p=0.0778) was observed. CONCLUSIONS: The prevalence of chronic post
      mastectomy pain was lower in our study comparing to studies in other countries.
      The reason remains obscure in spite of detailed analysis.

PMID- 16634481
TI  - [Percutaneous sacroplasty in sacral insufficiency fracture treatment].
AB  - Stress (insufficient) sacral bone fracture is a seriously painful disease with
      discussed and disunited therapy. Older women sufferig from osteoporosis create
      the main group in which this fracture occurs. Clinically, serious pain in sacral
      area is the most common symptome. This pain may last for a long time when treated
      conservatively and it can lead to pacient's immobilization with related
      comorbidity. In 2% of patients, neurological complications can be observed.
      Authors present summary of published studies and demonstrate an own case treated
      using percutaneous sacroplasty.

PMID- 16634482
TI  - [Beer and cancer--new findings].

PMID- 16634483
TI  - [Ideas and work of professor MUDr: Vladimir Vondracek DrSc. in relation to the
      development of contemperary psychiatry].

PMID- 16634484
TI  - [Discussion of the paper of Dr. M. Spala "Impact factor-- good servant, but a bad
      master"].

PMID- 16634485
TI  - [Discussion to the paper of doc. M. Spala "impact factor good servant, but a bad
      master"].

PMID- 16634486
TI  - [The most eminent personalities of the Prague Medical Faculty].

PMID- 16634487
TI  - "Open access" to scientific literature.

PMID- 16634488
TI  - Commentary on: Bone regeneration in standardized bone defects with autografts or
      bone substitutes in combination with platelet concentrate: a histologic and
      histomorphometric study in the mandibles of minipigs.

PMID- 16634489
TI  - Influence of implant abutment type on stress distribution in bone under various
      loading conditions using finite element analysis.
AB  - PURPOSE: The purpose of this study was to investigate the effect of 3 different
      abutment types on the stress distribution in bone with inclined loads using
      finite element analysis. MATERIALS AND METHODS: The 1-body, internal-hex, and
      external-hex implant systems were modeled to study the effect of abutment type on
      stress distribution in bone. The bone model used in this study comprised compact
      and spongious bone assumed to be homogeneous, isotropic, and linearly elastic.
      RESULTS: In the case of the 1-piece implant, the load was transferred evenly not
      only in the implant system but also in bone. However, the maximum Von Mises
      stress generated in bone with the 1-piece implant was always higher than that
      generated with the internal-hex implant, regardless of load angle inclination. In
      the case of the internal-hex implant, the contact condition with friction between
      abutment and implant in the tapered joints and at abutment neck reduced the
      effect of bending caused by horizontal component of inclined load. The maximum
      Von Mises stress in bone was the highest for the external-hex implant.
      DISCUSSION: It was found that the internal-hex implant system generated the
      lowest maximum Von Mises stresses for all loading conditions because of reduction
      of the bending effect by sliding in the tapered joints between the implant and
      abutment. CONCLUSIONS: It was concluded that abutment type has significant
      influence on the stress distribution in bone because of different load transfer
      mechanisms and the differences in size of the contact area between the abutment
      and implant.

PMID- 16634490
TI  - Effects of fluoride-modified titanium surfaces on osteoblast proliferation and
      gene expression.
AB  - PURPOSE: The objective of this study was to test the hypothesis that fluoride
      modified titanium surfaces would enhance osteoblast differentiation. Osteoblast
      growth on a moderately rough etched fluoride-modified titanium surface
      (alteration in cellular differentiation) was compared to osteoblast growth on the
      same surface grit-blasted with titanium dioxide. The potential role of nanometer
      level alterations on cell shape and subsequent differentiation was then compared.
      MATERIALS AND METHODS: Human embryonic palatal mesenchymal (HEPM) cultures were
      incubated on the respective surfaces for 1, 3, and 7 days, followed by analysis
      for cell proliferation, alkaline phosphatase (ALP) -specific activity, and mRNA
      steady-state expression for bone-related genes (ALP, type I collagen,
      osteocalcin, bone sialoprotein [BSP] II, Cbfa1, and osterix) by real-time
      polymerase chain reaction (PCR). RESULTS: The different surfaces did not alter
      the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II.
      However, Cbfa1 expression on the fluoride-modified titanium surface was
      significantly higher (P < .001) at 1 week. The number of cells on this surface
      was 20% lower than the number of cells on the surface TiO2-blasted with 25-microm
      particles but not significantly different from the number of cells on the surface
      TiO2-blasted with 125-microm particles. Cells grown on all the titanium surfaces
      expressed similar levels of ALP activity. CONCLUSIONS: The results indicated that
      a fluoride-modified surface topography, in synergy with surface roughness, may
      have a greater influence on the level of expression of Cbfa1 (a key regulator for
      osteogenesis) than the unmodified titanium surfaces studied.

PMID- 16634491
TI  - Histomorphometric and fluorescence microscopic evaluation of interfacial bone
      healing around 3 different dental implants before and after radiation therapy.
AB  - PURPOSE: Radiation therapy influence on bone healing around 3 types of endosseous
      dental implants in dogs was evaluated. MATERIALS AND METHODS: Implants with 3
      different surfaces (A = machined commercially pure titanium screws, B =
      commercially pure titanium plasma spray-coated cylinders, C = hydroxyapatite [HA]
      -ceramic coated cylinders) were first implanted unilaterally into the right
      posterior edentulous mandibles of 7 dogs as nonirradiated controls. After 12
      weeks without functional loading and after sequential fluorochrome labeling these
      implants were retrieved by block dissection. In this same surgery, implants were
      placed on the contralateral side. Three weeks postimplantation the implant
      containing hemimandibles were Cobalt 60 irradiated with the biologic equivalent
      of 5,000 cGy. Twelve weeks postimplantation and after labeling these irradiated
      implants were retrieved at sacrifice. On scanning electron, light, and
      fluorescence microscopic images of undecalcified longitudinal ground sections of
      the implants with surrounding tissues, percent bone-to-implant contact (% BIC),
      bone formation, and remodeling were histometrically and subjectively evaluated.
      RESULTS: Woven bone formation started 1 week after implantation at the implant
      interfaces on both the nonirradiated and the irradiated sides. Average BICs
      (total/cortical/spongious bone bed) of 26%/49%/36% for surface A, 46%/48%/64% for
      surface B, and 81%/83%/78% for surface C were observed. In the irradiated
      hemimandibles average BICs (total/cortical/spongious bone bed) were reduced to
      11%/9%/4% for surface A, 43%/46%/43% for surface B, and 63%/85%/76% for surface
      C, with increased resorption of peri-implant bone and retarded bone formation
      after irradiation. DISCUSSION: Reductions of total % BIC in all irradiated
      implants, though not statistically significant, were significant (P < or = .05)
      on implant surfaces A and B in the spongious bone bed. CONCLUSION: Retarded bone
      formation on surfaces A and B in the spongious bone bed represented a more
      radiation-sensitive situation at the time of radiation onset compared to advanced
      bone formation and maturation at surface C.

PMID- 16634492
TI  - Different substitute biomaterials as potential scaffolds in tissue engineering.
AB  - PURPOSE: To find the optimal scaffold for tissue-engineered bone, one approach is
      to test existing biomaterials on their suitability as scaffolds. In this study,
      the suitability of different alloplastic and xenogenic biomaterials as scaffolds
      for ex vivo osteoblast cultivation was investigated. MATERIALS AND METHODS:
      Normal human osteoblast cells were cultured on the surface of bovine collagenous
      materials, bovine hydroxyapatite, porcine gelatin, synthetic polymer, and
      collagen-containing bovine hydroxyapatite, and the investigation of proliferation
      was performed after 24, 72, and 120 hours. Measurement of the differentiation
      marker alkaline phosphatase and osteocalcin was made after 20 days of incubation.
      RESULTS: The obtained data showed significantly higher proliferation and
      differentiation rates in cells cultivated on collagen-rich biomaterials in
      comparison to noncollagenous or collagen-poor biomaterials (P < .05). DISCUSSION:
      In tissue engineering the scaffold should be biocompatible and serve as a proper
      matrix for the cells to produce the new structural environment of extracellular
      matrix ex vivo. Collagen supports initial cell attachment and cell proliferation,
      allowing immature osteogenic cells to differentiate into mature osteoblasts, but
      collagen may not be the only dominating factor for cell-matrix interaction during
      ex vivo bone formation. CONCLUSION: These data suggest that a 3-dimensional
      collagen matrix can provide a more favorable environment for the attachment,
      proliferation, and differentiation of in vitro osteoblastlike cells, at least
      until the initial stage of differentiation, than noncollagenous biomaterials.

PMID- 16634493
TI  - Osteoblast attachment on titanium disks after laser irradiation.
AB  - PURPOSE: Osteoblast attachment on titanium surfaces is necessary to achieve new
      bone formation and osseointegration. The purpose of this study was to examine
      osteoblast attachment on irradiated titanium disks. MATERIALS AND METHODS:
      Machined, hydroxyapatite (HA)-coated, sandblasted, and titanium plasma-sprayed
      (TPS) surfaces were irradiated with either a carbon dioxide (CO2) or an
      Er,Cr:YSGG laser. A control group of nonirradiated disks was also examined.
      Osteoblast cultures were cultivated on the titanium disks and examined with
      scanning electron microscopy. RESULTS: The findings demonstrated that osteoblasts
      could be grown on all of the surfaces. Pseudopodia and a spread of cells that
      demonstrated maturation were observed on the lased irradiated titanium disks.
      CONCLUSIONS: The data show that laser irradiation of titanium surfaces may
      promote osteoblast attachment and further bone formation.

PMID- 16634494
TI  - Distraction osteogenesis versus autogenous onlay grafting. Part II: biology of
      regenerate and onlay bone.
AB  - PURPOSE: Few studies have directly compared the quality of bone generated by
      distraction osteogenesis with that generated by autogenous onlay grafting. The
      purpose of this study was to compare rates of bone turnover at 5 months in bone
      produced by distraction osteogenesis and onlay grafting. MATERIALS AND METHODS:
      Alveolar defects created in jaws of American foxhounds were augmented with
      distraction osteogenesis or onlay grafting and allowed to heal for 5 months. The
      animals were then sacrificed and the jaws were resected and prepared for
      decalcified and undecalcified histologic examination. RESULTS: Both procedures
      produced bone containing a mixture of haversian systems and trabecular bone. A
      significantly greater ratio of osteoblast-covered bone surface to total
      trabecular bone surface (mean +/- SEM) was noted in distraction bone (0.124 +/-
      0.049) compared to onlay bone (0.081 +/- 0.048) or control host bone (0.085 +/-
      0.042 microm) (P < .05). In addition, significantly (P <.05) greater numbers of
      osteoclasts per microm of bone surface were noted in distraction bone (0.939 +/-
      0.07) compared to onlay bone (0.605 +/- 0.06) or control host bone (0.725 +/-
      0.08). No differences in rates of mineralization were noted between the groups.
      DISCUSSION: While bone from both experimental groups appeared adequate for
      implant placement, distraction bone appeared to be remodeling at a higher rate
      than either onlay or control bone. CONCLUSION: Given that the state of healing of
      the bone in each of these comparative groups was examined at a static point in
      time, it is premature to draw conclusions about the efficacy of one procedure
      over the other.

PMID- 16634495
TI  - Three-year data from a randomizd, controlled study of early loading of single
      stage dental implants supporting maxillary full-arch prostheses.
AB  - PURPOSE: The aim of this 3-year randomized controlled trial (RCT) was to compare
      biologic and technical treatment outcomes and patient satisfaction after early (<
      or = 14 days postimplantation) loaded implants with those of implants loaded
      after a healing period of 3 to 4 months in the edentulous maxilla. MATERIALS AND
      METHODS: Twenty-four patients with completely edentulous maxillae were randomized
      into a test group (n = 16) and a control group (n = 8). All patients received 5
      or 6 solid screw-type titanium implants with sandblasted, large-grit, acid-etched
      (SLA) surfaces. In total, 142 implants were placed and 139 implants were loaded
      with full-arch prostheses. Clinical assessments were obtained at loading and
      after 3, 6, 12, 24, and 36 months. Radiographs of implants and existing teeth
      were taken at loading; after 6, 12, 24, and 36 months; and at 12, 24, and 36
      months, respectively. RESULTS: The cumulative implant success rate 3 years after
      loading was 100%. At the 3-year examination the mean (P < or = .005), distal (P <
      or = .005), and mesial (P > .05) crestal bone levels were better in the test
      group. No significant differences between the test and control groups were noted
      for any other outcome measure. The most common adverse event in both groups was
      tooth-crown fracture. DISCUSSION: A review of the literature, both printed and
      electronic, revealed no study fulfilling the criteria of an RCT dealing with the
      early loading of maxillary full-arch prostheses. This study fulfills those
      criteria. CONCLUSION: In this study population it has been concluded that the
      early (approximately 2 weeks) loading protocol is a viable alternative to the
      standard (3 to 4 months) protocol in the rehabilitation of a completely
      edentulous maxilla with a complete implant-supported fixed prosthesis.

PMID- 16634496
TI  - Changes in crestal bone levels for immediately loaded implants.
AB  - PURPOSE: The authors' objective was to measure crestal bone level change in
      subjects with immediately loaded implants and to identify risk factors associated
      with changes in bone level. MATERIALS AND METHODS: A retrospective cohort study
      design was used. The sample comprised subjects who had had endosseous implants
      placed and immediately loaded between July 2001 and July 2003. Demographic,
      health status-related, anatomic, implant-specific, prosthetic, and surgical
      variables were examined. The primary outcome variable was change in crestal bone
      level over time. Appropriate uni-, bi-, and multivariate statistics were
      computed. RESULTS: The sample comprised 174 subjects who received 347 immediately
      loaded implants. The mean duration of radiographic follow-up was 6.9 +/- 4.0
      months, respectively. Mean changes in radiographic bone level were -0.5 mm and 
      0.6 mm on the mesial and distal surfaces, respectively, after a mean of 6.9
      months of radiographic follow-up. Using least squares methods, it was estimated
      that radiographic bone levels would be -1.0 mm and -0.8 mm on the mesial and
      distal surfaces, respectively, at 12 months. The multivariate model revealed that
      radiolucency at or adjacent to implant site was associated with an increased risk
      of crestal bone loss (odds ratio, 1.88; 95% CI, 1.00 to 3.60). Twelve months
      after placement, 92.5% of implants had had < or = 1.5 mm of crestal bone loss.
      DISCUSSION: The results of this study were comparable to the results of other
      studies comparing immediate loading to delayed loading. Further research to
      estimate long-term changes in crestal bone loss and to identify risk factors for
      bone loss with immediate loading is recommended. CONCLUSION: This study suggests
      that crestal bone level changes with immediately loaded implants were within the
      recommended range for 92.5% of the evaluated implants. The mandible showed a
      higher risk for crestal bone loss compared to the maxilla.

PMID- 16634497
TI  - Evaluation of peri-implant microbiota using the polymerase chain reaction in
      completely edentulous patients before and after placement of implant-supported
      prostheses submitted to immediate load.
AB  - PURPOSE: To evaluate, by means of the polymerase chain reaction (PCR), the
      presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and
      Prevotella intermedia in the mandibular arch of completely edentulous subjects
      before implant placement and 4 and 6 months after the placement of mandibular
      implant-supported fixed prostheses. MATERIALS AND METHODS: Fifteen patients had
      bacterial plaque collected with sterile paper points before implant placement
      (ie, when they were completely edentulous) and at 3 sites on the peri-implant
      sulci displaying the largest probing depths after placement of 5 implants.
      RESULTS: For the edentulous arch, A actinomycetemcomitans was detected in 13.3%
      of subjects, P intermedia was detected in 46.7% of subjects, and there was no
      detection of P gingivalis. After 4 and 6 months of implant placement, A
      actinomycetemcomitans was detected in 60% and 73.3% respectively; P intermedia in
      46.7% and 53.3% respectively; and P gingivalis in 46.7% and 53.3%, respectively.
      DISCUSSION: Future diagnosis should not be restricted to distinguishing
      individuals at risk of peri-implant disease. Such individuals should be
      identified by the employment of microbiologic methods and knowledge of the
      multifactorial nature of the host response to the action of microorganisms.
      CONCLUSIONS: The longer the implants were in the oral cavity, the higher the
      occurrence of A. actinomycetemcomitans, P. gingivalis, and P. intermedia in the
      peri-implant sulci of completely edentulous patients rehabilitated with
      mandibular implant-supported fixed prostheses was, without any clinical or
      radiographic evidence indicating peri-implant disease in the studied period.

PMID- 16634498
TI  - The importance of implant surface characteristics in the replacement of failed
      implants.
AB  - PURPOSE: The purpose of the study was to compare the failure rates of implants
      with either a machined surface or a TiUnite surface used to replace failing
      implants. MATERIALS AND METHODS: The files of 578 patients, ie, of all patients
      who were treated at the Department of Periodontology of the University Hospital
      in Leuven by means of oral implants during 3 recent consecutive years, were
      analyzed. The implants included in the study had an observation time ranging from
      9 to 49 months. All patients had been provided with Branemark System implants.
      Only 2 types of implant surfaces were used: machined and TiUnite. Data collection
      and analysis focused on the replacement implants, ie, implants placed at sites
      where the original implants had failed. Data were statistically analyzed by means
      of Statistica for Windows Software version 5.1; a Fisher exact P test was used.
      The level of significance was set at P = .05. RESULTS: A total of 41 patients
      experienced the nonintegration of 58 implants. Of those, 29 implants with a
      machined surface were replaced by implants with the same surface. Six of the
      replacement implants failed. Nineteen machined-surface implants were replaced by
      TiUnite surface implants; 1 failed. Ten TiUnite-surface implants were replaced by
      implants with the same surface; none failed. The difference in failure rate
      between machined-surface replacement implants and TiUnite replacement implants
      was statistically significant (P = .05). DISCUSSION: In addition to the usual
      patient-related compromising factors, replacement of a failing implant involves
      the challenge of achieving osseointegration in a nonpristine bone site. In the
      present study, implants with TiUnite surfaces were associated with fewer failures
      than machined-surface implants under the same conditions. CONCLUSION: An improved
      implant surface such as TiUnite may offer a better prognosis when a failed
      implant has to be replaced at the same site.

PMID- 16634499
TI  - Influence of prosthetic parameters on the survival and complication rates of
      short implants.
AB  - PURPOSE: Implants shorter than 10 mm can be a long-term solution for sites with
      limited bone height. The purpose of this study was to determine the influence of
      some prosthetic factors on the survival and complication rates. MATERIALS AND
      METHODS: Two hundred sixty-two short machined-surface Branemark System implants
      were consecutively placed in 109 patients and followed for a mean of 53 months.
      The prosthetic parameters were recorded, and the data were examined for relation
      to peri-implant bone loss and biologic or biomechanical complications. RESULTS:
      Relatively few crown-to-implant (C/I) ratios were < 1 or > 2 (16.2%). Occlusal
      table (OT) width ranged from 5.4 to 8.3 mm. Opposing dentition was most often
      natural teeth, a fixed prosthesis supported by natural teeth, or an implant
      supported fixed restoration. Occlusion with a normal buccolingual
      maxillomandibular relationship was found in 72.7% of the cases. No significant
      difference in peri-implant bone loss was correlated with C/I ratio or OT. Neither
      cantilever length nor bruxism had a significant effect on peri-implant bone loss.
      Mean bone loss was 0.74 +/- .65 mm. The difference in the complication rate (15%
      overall) between the bruxer and the nonbruxer group was not statistically
      significant (P = .51). One implant was lost in a heavy bruxer after 7 years of
      function. DISCUSSION: Increased C/I and OT values do not seem to be a major risk
      factor in cases of favorable loading. In 67% of the cases, the mesiodistal length
      of the prosthesis was less than the corresponding natural tooth length, which may
      have contributed to better load distribution and more favorable results.
      CONCLUSIONS: Short implants appear to be a longterm viable solution in sites with
      reduced bone height, even when the prosthetic parameters exceed the normal
      values, provided that force orientation and load distribution are favorable and
      parafunction is controlled.

PMID- 16634500
TI  - Removal torque of miniscrews used for orthodontic anchorage--a preliminary
      report.
AB  - PURPOSE: Implant anchors such as miniscrews and miniplates have been loaded
      immediately for anchorage during orthodontic treatment. The purpose of this study
      was to measure the removal torque of immediately loaded miniscrews after clinical
      usage and to determine the possible factors associated with this value. MATERIALS
      AND METHODS: From 29 patients with malocclusions, 46 miniscrews were removed, and
      removal torque was measured with a torque gauge. Removal torque values were
      subjected to statistical analysis for possible association of different clinical
      characteristics. RESULTS: The mean removal torque value was 1.10 kg x cm, and
      removal torques for 50% of the implants were greater than 0.89 kg x cm (8.7 N x
      cm). Removal torque values were significantly higher in the mandible than in the
      maxilla. The removal torques of 15-mm and 17-mm miniscrews were significantly
      higher than those of 13-mm miniscrews. Therefore, the site of implantation and
      miniscrew length were important factors associated with removal torque. However,
      there was no significant correlation between the removal torque value and age,
      gender, healing time, or time in function. DISCUSSION: When miniscrews are used
      as anchorage for uprighting tipped molars, excessive torque in a counterclockwise
      direction may loosen them. From the measurements obtained in this investigation,
      miniscrews can sufficiently sustain an uprighting moment. CONCLUSION: The removal
      torque values of the majority of miniscrews in this study population when loaded
      immediately as orthodontic anchorage were greater than 0.89 kg x cm, and this was
      sufficient for these implants to fulfill their purpose as anchors in 3
      dimensional tooth movements.

PMID- 16634501
TI  - Quantitative evaluation of bone density using the Hounsfield index.
AB  - PURPOSE: The primary aims of this retrospective study were to: (1) evaluate bone
      quality in different segments of the edentulous jaw and correlate it with
      demographic data and (2) establish a quantitative and objective assessment of
      bone quality based on the Hounsfield scale. MATERIALS AND METHODS: One hundred
      one randomly selected computerized tomographic (CT) scans were used for the
      analysis. Edentulous segments ranging from 10 to 30 mm were selected for
      evaluation, and the findings were analyzed and correlated to demographics.
      Implant recipient sites were evaluated visually for bone classification by 2
      independent examiners. The same sites were subsequently evaluated digitally using
      the Hounsfield scale, and the results were correlated with the visual
      classification. RESULTS: The 4 quadrants of the mouth displayed Hounsfield unit
      (HU) values ranging from -240 HU to 1,159 HU. The highest unit/mean density value
      (559 +/- 208 HU) was found in the anterior mandible, followed by 517 +/- 177 HU
      for the anterior maxilla, 333 +/- 199 HU for the posterior maxilla, and 321 +/-
      132 HU for the posterior mandible. There was no association between the
      Hounsfield value and density and age or gender. When subjective bone quality was
      correlated to Hounsfield index findings, only the relationship between HU and
      type 4 bone was found to be significant. CONCLUSIONS: Knowledge of the Hounsfield
      value as a quantitative measurement of bone density can be helpful as a
      diagnostic tool. It can provide the implant surgeon with an objective assessment
      of bone density, which could result in modification of surgical techniques or
      extended healing time, especially in situations where poor bone quality is
      suspected.

PMID- 16634502
TI  - Effect of flapless surgery on pain experienced in implant placement using an
      image-guided system.
AB  - PURPOSE: The aim of this study was to compare the pain experienced after implant
      placement with 2 different surgical procedures: a flapless surgical procedure
      using an image-guided system based on a template and an open-flap procedure.
      MATERIALS AND METHODS: The study population consisted of 60 patients who were
      referred for implant placement. One group consisted of 30 patients who were
      referred for the placement of 80 implants and treated with a flapless procedure.
      The other group consisted of 30 patients who were referred for the placement of
      72 implants with a conventional procedure. Patients were selected randomly. They
      were requested to fill out a questionnaire using a visual analog scale (VAS) to
      assess the pain experienced and to indicate the number of analgesic tablets taken
      every postoperative day from the day of the surgery (DO) to 6 days after surgery
      (D6). RESULTS: The results showed a significant difference in pain measurements,
      with higher scores on the VAS with open-flap surgery (P < .01). Pain decreased
      faster with the flapless procedure (P = .05). The number of patients who felt no
      pain (VAS = 0) was higher with the flapless procedure (43% at DO versus 20%).
      With the flapless procedure, patients took fewer pain tablets (P = .03) and the
      number of tablets taken decreased faster (P = .04). DISCUSSION: Minimally
      invasive procedures may be requested by patients to reduce their anxiety and the
      pain experienced and thus increase the treatment acceptance rate. CONCLUSION:
      With the flapless procedure, patients experienced pain less intensely and for
      shorter periods of time.

PMID- 16634503
TI  - Accuracy in computer-aided implant surgery--a review.
AB  - The objective of this article was to review the different factors and limitations
      influencing the accuracy of computer-aided implant surgery. In vitro and in vivo
      accuracy studies of articles and congress proceedings were examined. Similar
      results using bur tracking as well as image-guided template production techniques
      have been reported, and both methods allow for precise positioning of dental
      implants. Compared to the conventional technique, this sophisticated technology
      requires substantially more financial investment and effort (computerized
      tomographic imaging, fabrication of a registration template, intraoperative
      referencing for bur tracking, or image-guided manufacturing of a surgical
      template) but appears superior on account of its potential to eliminate possible
      manual placement errors and to systematize reproducible treatment success. The
      potential for the protection of critical anatomic structures and the esthetic and
      functional advantages of prosthodontic-driven implant positioning must also be
      considered. However, long-term clinical studies are necessary to confirm the
      value of this strategy and to justify the additional radiation dose, effort, and
      costs.

PMID- 16634504
TI  - Flapless approach for removal of bone graft fixing screws and placement of dental
      implants using computerized navigation: a technique and case report.
AB  - This article presents a technique for the removal of the screws used to fix a
      bone graft and for the placement of dental implants in a flapless approach that
      utilizes the tracking technology of a computerized navigation system. A 24-year
      old female patient injured in a terrorist bombing suffered from tooth loss and a
      bone defect in the maxilla. The area was grafted with bone from the chin in
      preparation for the placement of dental implants. Four months following the
      grafting procedure, the fixing screws were removed and the dental implants were
      placed in a flapless approach by the application of a specialized computerized
      navigation system. This technique emphasizes the potential of computerized
      navigation approaches in the facilitation of minimally invasive oral surgery.

PMID- 16634505
TI  - A prosthodontic technique to improve the simplicity and the efficacy of angled
      abutments for divergent implant situations: a technical note.
AB  - Esthetic demands and nonparallel situations between the axial direction of the
      suprastructure and the implant require angulation of the abutment. The Conical
      Seal design avoids microleakage and micromovements after the abutment has been
      seated and finally retained via screw. However, there is no protection against
      rotation during the fixation procedure. Therefore, a control device and/or method
      for a reproduction of correct seating during each treatment step of permanent
      prosthesis fabrication is desirable. The purpose of this investigation was to
      develop a device to ensure the correct seating by less expensive, safer, easier,
      and more precise methods. The sequence of components and the standard procedure
      required modification: in the modified procedure, the impression is made at the
      implant level, and the straight implant replica is embedded in the laboratory
      cast. The angled abutment needs modification by grinding to create small margins
      in the mesial, distal, and palatal walls. Three materials that are used in daily
      dental practice are combined to fabricate an individual transfer device. Direct
      waxup of the restoration onto the angled abutment without a prefabricated
      component shortens the laboratory processing. The modified sequence and
      procedure, small alterations of the angled abutment, and an individual transfer
      device can simplify the transfer procedures, improve clinical performance and
      applicability, and shorten chair time.

PMID- 16634509
TI  - Our health, our care, our say.

PMID- 16634510
TI  - Barriers to care in postnatal depression.

PMID- 16634511
TI  - Suntan safety.

PMID- 16634512
TI  - Community-acquired pneumonia.

PMID- 16634513
TI  - Parenting, class and culture: exploring the context of childrearing.
AB  - This paper highlights the central role of social class in shaping experiences of
      childrearing. Drawing on material from qualitative interviews with a range of
      working class mothers it explores and contextualises day-to-day family practices.
      It examines the different ways in which parents cope with disadvantage and shows
      how their decisions and practices are grounded in a material and social reality.
      In contrast to evaluative and outcome-focused literature on parenting, it
      demonstrates how decisions and practices that make less sense from a middle class
      vantage point shift their meaning when viewed from a working class perspective.
      The paper illustrates how the promotion of parenting 'skills' as neutral
      technical tips obscures normative, culturally specific assumptions about what
      constitutes successful childrearing. The implications of this for health
      visitors' practice will be considered.

PMID- 16634514
TI  - The benefits of using the Neonatal Behavioural Assessment Scale in health
      visiting practice.
AB  - Health visitors have a key role to play in the government's public health
      strategy with its emphasis on early identification of vulnerable children. This
      paper raises the profile of infant mental health as a public health priority and
      outlines the vital importance of a loving early relationship between an infant
      and primary caregiver for a child's healthy development. It describes the
      Neonatal Behavioural Assessment Scale (NBAS) and the appropriateness of its use
      by health visitors. This tool has been underused in the UK, but is being used in
      clinical practice and research in many other countries, such as the USA. It can
      add value to the assessments already being carried out by health visitors and can
      contribute to partnership working with parents as together they observe how the
      infant interacts with and organises his/her world. The NBAS enables health
      visitors to demonstrate to parents an infant's strengths and abilities, together
      with any needs for extra care giving. This assessment has been shown to improve
      developmental outcomes by enhancing the infant-caregiver relationship, and
      provides health visitors with the opportunity to consolidate their relationship
      of trust with families.

PMID- 16634515
TI  - Immunisation hotline calls as five-in-one vaccine introduced.
AB  - Announcement of the introduction of the five-in-one vaccine (DTaP/IPV/Hib) into
      the primary immunisation schedule was made on 9 August 2004. In this study all
      calls to the immunisation hotline were recorded between 9 August 2004 and 19
      November 2004, noting who called and the nature of their enquiry. A total of 208
      calls were received during the study period, and of these 23 (11.1%) related to
      the new vaccine. Calls were from parents (10/23, 43%), health visitors (9/23,
      39%) and practice nurses (3/23, 13%). A variety of themes were covered in calls
      including local availability of the five-in-one vaccine, vaccine safety, mercury
      content and efficacy. Calls not connected with the new vaccine concerned mostly
      adolescent MMR (17.3%) as there was a local mumps epidemic. Others related to
      clarification of a child's immunisation status (13.5%), primary MMR immunisation
      (13.5%), vaccination scheduling or administration difficulties (12%), other
      schedule (12.5%) and non-schedule vaccines (2.4%), vaccine reactions (2.4%),
      travel vaccines (6%), BCG (6%), and a few miscellaneous queries (3%). Overall
      questions about the new five-in-one vaccine accounted for an extra 23 calls to
      the immunisation hotline during the study period (11.1% of calls).

PMID- 16634516
TI  - Speak out in a climate of fear.

PMID- 16634517
TI  - Autistic spectrum disorders 2: diagnosis and management.
AB  - As many as six in every 1000 children may be affected by an autistic spectrum
      disorder. The previous article of this two-part series discussed the distinction
      between autism, Asperger's syndrome and pervasive developmental disorder, and
      examined the assessment process. This article looks at potential differential
      diagnoses that must be considered, as well as conditions associated with autism.
      Many theories about the causes of autism have been suggested, including the MMR
      vaccine. Recent research has suggested that there is no link between the vaccine
      and autism. There is no cure for autism, but intervention and management
      techniques should be aimed at educating parents and carers about the disorder and
      behavioural interventions to aid the child's skills development.

PMID- 16634518
TI  - Case management to cut non-elective admissions.

PMID- 16634519
TI  - Evaluation of subcutaneously-implanted glucose sensors for continuous glucose
      measurements in hyperglycemic pigs.
AB  - BACKGROUND: Subcutaneously-implanted glucose sensors for continuous glucose
      monitoring have the potential to replace serial blood glucose measurements. The
      objective of the present study was to test whether continuous glucose
      measurements could be obtained with glucose sensors implanted in the subcutis of
      pigs. Moreover, the in vivo biocompatibility of the sensors was evaluated since
      an inflammatory reaction may lead to drift in sensor-signaling. MATERIALS AND
      METHODS: Two types of glucose sensor were implanted for 3 days in the subcutis of
      hyperglycemic pigs. The plasma glucose concentration was correlated to the sensor
      outputs, and tissue was sampled for histological evaluation. RESULTS: There was a
      good correlation between the interstitial fluid and blood glucose levels.
      However, there was a statistical significantly difference in linearity from days
      0 and 1 to day 2 (p<0.001) and variations in the sensitivity and background
      current of individual sensors were observed over time. The tissue reaction caused
      by the sensors was a mild focal subacute fibrinous dermatitis. CONCLUSION:
      Continuous glucose measurement can be achieved by glucose sensors implanted in
      the subcutis of pigs. The observed drift in sensor signals over time may have
      been caused by heterophils, macrophages and/or fibrinogen at the tissue-sensor
      interface.

PMID- 16634520
TI  - Ovine cord blood accommodates multipotent mesenchymal progenitor cells.
AB  - BACKGROUND: Stem cells derived from umbilical cord blood display mesenchymal
      multipotency and can differentiate into osteoblasts, chondroblasts and
      adipoblasts in vitro under defined stimuli. Although sheep have been used as
      experimental models for investigations on xenoreactivity after transplantation of
      stem cells isolated from human umbilical cord blood, the potential of ovine cord
      blood stem cells to differentiate has been examined to date. MATERIALS AND
      METHODS: Mononuclear cells from the placentoms of 3 lambs were isolated via
      density gradient centrifugation and cultivated. After expansion up to 3 passages,
      the cells were stimulated to differentiate towards osteogenic (dexamethasone,
      ascorbic-acid-2-phosphate, beta-glycerolphosphate), chondrogenic (TGF-beta3,
      insulin, transferrin, selenium, dexamethasone, ascorbic-acid-2-phosphate) and
      adipogenic (indomethacine, insulin, 3-isobutyl-1-methylxanthine, dexamethasone)
      lines for 20 days. The cells were characterized morphologically by transmission
      and phase contrast light microscopy during lineage-specific stimulation.
      Immunocytochemistry and conventional stains were used to detect lineage-typical
      markers: fat vacuoles and peroxisome proliferation-acitivated receptor gamma2
      (PPAR) served to detect adipoblasts, whereas osteopontin (OP) was used to
      characterize osteoblasts. A positive antibody reaction to collagen II and
      chondrogenic oligomeric protein (COMP) revealed the presence of chondroblasts.
      RESULTS: The osteogenic line formed bone nodules, adipogenic cells developed
      lipid droplets and the cells of the chondrogenic line showed typical chondroblast
      like morphology. CONCLUSION: It was demonstrated that ovine mesenchymal stem
      cells, derived from umbilical cord blood (sheep unrestricted somatic stem cells,
      S-USSCs), can be isolated via gradient density centrifugation and expanded in
      vitro. Under lineage-specific stimulation, S-USSCs differentiated into osteo-,
      chondro- and adipoblasts with typical morphological characteristics. Significant
      quantitative differences between the stimulated and control groups in lineage
      typical immunocytochemical markers verified these findings.

PMID- 16634521
TI  - Kinetic radical-scavenging activity of melatonin.
AB  - Carbon-centred free radicals can be involved in damage to biological systems
      under hypoxiclanoxic conditions as well as in ischaemia/reperfusion injury. The
      antioxidant activities of melatonin against carbon-centred radicals are poorly
      understood. The aim of this study was to investigate the antioxidant properties
      of melatonin against carbon-centred radicals in a biomimetic model system
      consisting of growing methyl methacrylate (MMA) radicals (poly-MMA radicals,
      PMMA*). The kinetics of the polymerization of MMA initiated by thermal
      decomposition of 2,2'-azobis(isobutyronitrile) (AIBN; R* radical) or benzoyl
      peroxide (BPO; PhCOO* radical) in the presence of melatonin were investigated by
      the induction period method under nearly anaerobic conditions. As melatonin
      concentrations increased, the length of the induction period (IP) increased, but
      for the BPO system the IP reached a plateau at a molar ratio of BPO to melatonin
      of 5:1, indicating that the oxidation of melatonin by PhCOO* was limited. At low
      concentrations of melatonin, the stoichiometric factor (n, the number of free
      radicals trapped by the antioxidant moiety) for melatonin was approximately 2,
      but as the melatonin concentration increased the n value decreased markedly to
      0.1. These observations suggest that melatonin may possess catalytic activity
      contributing to radical avoidance. The initial rate of polymerization (Rp) in the
      BPO system was markedly suppressed by high concentrations of melatonin,
      suggesting a strong interaction between oxidative end-products formed from
      melatonin and PMMA*. Under conditions where n was about 2, the kinh values for
      melatonin in the BPO system and the AIBN system were 6.58 x 10(4) M(-1)S(-1) and
      2.49 x 10(3) M(-1)s(-1), respectively. In the BPO system, the kinh of melatonin
      was of a similar magnitude to that of a-tocopherol, whereas in the AIBN system
      the kinh of melatonin was 100-fold greater than that of tocopherol. The present
      findings suggest that melatonin may be able to scavenge harmful carbon-centred
      radicals in vivo.

PMID- 16634522
TI  - The natural chemopreventive compound indole-3-carbinol: state of the science.
AB  - The hydrolysis product of glucobrassicin, indole-3-carbinol (I3C), is metabolized
      to a variety of products, including the dimeric 3,3'-diindolylmethane (DIM). Both
      I3C and DIM exert a variety of biological and biochemical effects. Most of these
      effects appear to occur because I3C modulates several nuclear transcription
      factors. I3C induces phase I and phase II enzymes that metabolize carcinogens,
      including estrogens. Administration of either I3C or DIM results in increased 2
      hydroxylation of estrogens. I3C also enhances DNA repair by affecting several of
      the proteins involved in this process. I3C induces both G1 cell cycle arrest and
      apoptosis. All of these activities lead to anticancer effects. Although I3C has
      been shown to protect against tumor induction by some carcinogens, it has also
      been observed to promote tumor development in animal models. In humans, I3C and
      DIM affect the metabolism of estrogens. Concerns have been raised that I3C might
      increase the formation of estrogen metabolites that induce or promote cancer, but
      this has not been demonstrated. I3C has been found to be effective in treating
      some cases of recurrent respiratory papillomatosis, and it may have other
      clinical uses.

PMID- 16634523
TI  - In situ demonstration of improvement of liver mitochondria function by melatonin
      after cold ischemia.
AB  - In a previous investigation, reperfusion with a melatonin-containing medium was
      demonstrated to enhance bile production and tissue ATP levels in rat livers, cold
      preserved with University of Wisconsin (UW) or Celsior solutions, with respect to
      melatonin-free reperfusion; lipid peroxidation products in the perfusate were not
      influenced by the indole. This was ascribed to an increased efficiency of the
      hepatocyte mitochondria induced by melatonin. Reactive oxygen species (ROS)
      normally leak from the electron transfer chain in mitochondria and excessive ROS
      production is presumed to mediate ischemia-reperfusion (I/R) damage. A
      histochemical reaction was used to demonstrate ROS on the same model. Compared to
      the lobular zonation of ROS in control livers, the stained area of cold-preserved
      livers reperfused without melatonin was restricted to a narrow portal region, in
      keeping with the much lower ATP content. When reperfusion was performed with
      melatonin, the liver morphology was improved and the ROS reaction in hepatocytes
      more intense, though not reaching the control liver pattern. Sinusoidal cells
      were poorly-stained in both cases. In conclusion, with this different approach,
      melatonin was confirmed to improve mitochondrial performance and to discriminate
      parenchymal from sinusoidal cell behavior. Our observations confirm that
      melatonin mitigates I/R injury and support its potential in liver
      transplantation.

PMID- 16634524
TI  - Isolation of human myeloid dendritic cells from tumor tissue and peripheral
      blood.
AB  - BACKGROUND: Human myeloid dendritic cells (MDC) have been identified in human
      solid tumor tissue of head and neck squamous cell carcinoma (HNSCC), their
      cellular functions being strongly affected in this environment. The
      characterization of MDC differentiation and functions requires the establishment
      of highly efficient isolation procedures. MATERIALS AND METHODS: Human MDC were
      isolated from peripheral blood and solid HNSCC using density gradient
      centrifugation or preparation of single cell suspensions, respectively. The cells
      were isolated by "magnetic bead separation" using magnetically-labelled
      antibodies and were analyzed by flow cytometry. RESULTS: The isolation of human
      MDC from peripheral blood or solid HNSCC tissue resulted in highly enriched cell
      populations and revealed cell purities of about 90%. CONCLUSION: The scale of
      molecular investigations on human myeloid dendritic cells is restricted by the
      limited proportion of this cell type. Thus, highly efficient and gentle MDC
      isolation procedures are essential to characterize in vivo matured MDC.

PMID- 16634525
TI  - Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum.
AB  - BACKGROUND: Endothelin (ET-1) may play a role in the regulation of erection but
      this has not been conclusively demonstrated. Augmented cavernosal smooth muscle
      (CSM) contraction in the rat occurs following exposure to both ET-1 and
      phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the
      effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the
      erectile process. MATERIALS AND METHODS: Organ bath studies were performed on CSM
      strips of penises obtained from 12 age-matched New Zealand White rabbits. The
      effect of ET-1 and PE alone on CSM tone in the absence and presence of ETA
      (BQ123) and ETB (BQ788) antagonists was assessed. Tissue responses were measured
      as tension (newton, N). EC50 values are expressed as mean +/- S.E.M. RESULTS: PE
      (10(8) - 10(-4) M) and ET-1 (10(-10) - 10(-6) M) produced a concentration
      dependent contraction in rabbit CSM strips. The EC50 values were 1.7 x 10(-7) M
      +/- 1.1 and 3.4 x 10(-9) M +/- 1.5, respectively. BQ123 10(-5) M significantly
      inhibited ET-1-mediated CSM contractions more than BQ788 10(-5) M (both ANOVA
      p<0.01). The EC50 were 1.3 x 10(-6) M +/- 2.6 and 2.0 x 10(-7) M +/- 2.1,
      respectively. Neither the ETA or ETB receptor antagonist had a significant
      influence on alpha1-adrenergic receptor-mediated CSM contraction. CONCLUSION: ETA
      receptors may play a greater role than ETB receptors in ET-1-induced rabbit CSM
      contraction and the detumescence process. The a1-adrenergic-dependent pathway
      does not involve the ETA or ETB receptors.

PMID- 16634526
TI  - Enhancement of immune responses to neem leaf extract (Azadirachta indica)
      correlates with antineoplastic activity in BALB/c-mice.
AB  - An aqueous plant extract from Azadirachta indica and its chromatographic fraction
      F1 (neem extract) exerted immunomodulating and antimetastatic activities in BALB/
      c-mice. Regular subcutaneous administration of neem extract yielded significantly
      increased spleen weight and significant enhancement of peritoneal macrophage
      activity in the chemiluminescence assay, and activation marker CD-44 expression.
      The thymus weight and thymocyte counts did not show significant differences in
      the control and neem extract-treated groups, however, determination of peripheral
      blood cells revealed significant up-regulations of leukocyte subsets, the
      lymphocytes and monocytes. Flow cytometric analaysis of lymphocyte supopulations
      documented increased counts of CD-4 and CD-8 cells and an inreased activation
      marker expression on lymphocytes (CD-25) and monocytes (MAC-3) in neem-treated
      mice compared to the control animals. To evaluate the antimetastatic activity of
      neem extract, sarcoma L-1 cells and lymphosarcoma RAW cells were intravenously
      inoculated into BALB/c-mice. In these model systems the number of experimental
      lung and liver metastases decreased relevantly, however, biometrically non
      significantly in neem extract-treated animals, as compared to the control mice
      which received injections of saline solutions. Neem extract can be regarded as an
      immunomodulating and antimetastatic substance which holds promise for further
      experimental and clinical investigation.

PMID- 16634527
TI  - Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in
      female C3H/He mice.
AB  - The potential preventive effect of the synthetic pineal peptide Epitalon (Ala-Glu
      Asp-Gly) on spontaneous tumorigenesis in mice was studied. One-year-old female
      C3H/He mice were kept for 6.5 months under standard conditions. Epitalon was
      injected at a dose of 0.1 microg, 5 times a week. Long-term exposure to Epitalon
      in small doses did not show any toxic effect. Treatment with Epitalon decreased
      the number of tumor-bearing mice with malignant tumors and prevented the
      development of metastases. Spontaneous tumors of the reproductive organs (mammary
      glands and ovaries) were predominant in both groups of mice (control and
      experimental). The mammary gland tumors were different variants of invasive
      ductal carcinomas. In the ovaries, granulosa-cell tumors were found. Tumors were
      in the minority in other organs and had benign characteristics. In control mice,
      metastases were found in 3 out of 9 tumor-bearing mice, all of them being from
      tumors of the reproductive organs. Treatment with Epitalon slowed down the
      development of metastases from spontaneous tumors, and no metastases were found
      in the experimental mice. These data highlight the antimetastatic effect of
      Epitalon as part of its oncostatic properties.

PMID- 16634529
TI  - The role of basic-fibroblast growth factor (b-FGF) in cyclosporine-induced
      nephrotoxicity.
AB  - BACKGROUND: The effect of the b-fibroblast growth factor (b-FGF) on cyclosporine
      A (CsA)-induced nephrotoxicity in the rat kidney was investigated. MATERIALS AND
      METHODS: The rats were divided into six groups: A (control), B (b-FGF-treated),
      C, D: (CsA-treated and sacrificed on days 14 or 21), E, F (Cs A- and b-FGF-
      treated and sacrificed on days 14 or 21). The antibody mouse anti-rat CD31 was
      used to evaluate the kidney vessels present in histological preparations.
      RESULTS: The kidney vessels in group B were increased in comparison with the
      control group (p<0.05). Reduction of kidney vessels in groups C and D (p<0.05) in
      comparison with the controls was observed, while in groups E and F they were
      increased when compared to group C (p<0.05) and D (p<0.05), respectively.
      CONCLUSION: The angiogenic role of b-FGF was confirmed in normal rats and a
      possible "protective" role of b-FGF was shown in rat kidney with CsA-induced
      nephrotoxicity.

PMID- 16634528
TI  - NGF overexpression and distribution in cortical thymic epithelial cells of mice
      with experimentally-induced leukemia.
AB  - BACKGROUND: Thymic epithelial cells often form lymphoid-epithelial cell (LEC)
      complexes, thought to contribute both to normal T-cell differentiation and to
      leukemogenesis. The distribution of the nerve growth factor (NGF) and NGF
      immunoreactivity modulation of complex-forming thymus epithelial cells were
      studied in mice with experimental acute L1210 leukemia. MATERIALS AND METHODS:
      Light and electron microscopic methods and cell separation techniques were
      applied. RESULTS: Immunoperoxidase and immunogold labelling showed subcapsular
      and subseptal overexpression of NGF by epithelial cells in leukemic thymus. NGF
      immunopositive epithelial cells were closely associated with lymphoid cells. The
      increased immunoreactivity of epithelial cells correlated with LEC complex
      formation, including thymic nurse cell-like structures and rosettes in the
      external cortex. CONCLUSION: These results provide new structural and
      immunocytochemical evidence for intimate contact between NGF-producing epithelial
      cells and lymphoid cells and suggest that NGF immunoreactive LEC complexes are
      involved in thymic microenvironmental reorganization during leukemogenesis.

PMID- 16634530
TI  - PCNA, Ki-67 and hTERT in residual benign meningiomas.
AB  - BACKGROUND: Relapse in individual patients after incomplete/residual removal of
      meningiomas cannot be predicted by histology alone as re-growth occurs even in
      histologically benign meningiomas. MATERIALS AND METHODS: Proliferating cell
      nuclear antigen (PCNA), Ki-67 and human telomerase reverse transcriptase (hTERT)
      labelling indices were measured in histological sections derived from residual
      meningiomas in 37 patients to assess their relationship to relapse. The labelling
      index (LI) expressed the percentage of tumour cell nuclei immunoreactive for
      PCNA, Ki-67 or hTERT in 1,000 tumour cells counted per section. The histological
      specimens comprised the following 2 groups: (i) stable for at least 10 years
      after initial partial resection of residual meningiomas: 20 specimens; (ii)
      relapsing between 11 and 145 months after initial resection of residual
      meningiomas: 17 specimens. RESULTS: The proliferative activity and hTERT
      expression do not directly correlate with every relapse. The PCNA LI
      significantly differed in the relapsing group (10.8%) compared to the stable
      group (5.5%) (p=0.08). The Ki-67 LI also was higher in the relapsing group (2.5%)
      than in the stable group (2.0%), but not statistically significantly (p=0.9).
      hTERT LI was significantly higher in the relapsing group (27.8%) than in the
      stable group (7.2%) (p<0.01). CONCLUSION: The mean PCNA, Ki-67 and hTERT LI were
      higher in the relapsing group of residual meningiomas than in the stable group,
      although no statistical difference was found for PCNA and Ki-67. On the other
      hand, a statistical difference between the two groups of meningiomas was found
      for hTERT; however, it is no absolute predictor for relapse at the individual
      patient level.

PMID- 16634531
TI  - Safety and efficacy of local administration of contractubex to hypertrophic scars
      in comparison to corticosteroid treatment. Results of a multicenter, comparative
      epidemiological cohort study in Germany.
AB  - OBJECTIVES: To investigate the safety and efficacy of Contractubex administration
      to hypertrophic scars in routine out-patient practice and to compare it to
      corticosteroid treatment. PATIENTS AND METHODS: This was a multicenter,
      retrospective cohort study, based on 38 randomly selected practices
      representatively distributed in Germany, including dermatologists and general
      practitioners. Data from 859 patients fulfilling the inclusion criteria were
      assessed and analyzed. Of these, 771 patients were eligible for the per protocol
      treatment with Contractubex (n=555) and corticosteroid (n=216). The safety and
      efficacy of local administration of Contractubex to hypertrophic scars was
      compared to corticosteroid treatment. RESULTS: At the end of defined treatment
      periods (minimum 28 days for local therapy with 1 intralesional corticosteroid
      application), normalization of the pre-treatment pathological parameters
      (erythema, pruritus, consistency) of hypertrophic scars was more frequent (42.5%)
      after Contractubex per protocol treatment as compared to corticosteroid per
      protocol treatment (22.2%). After adjusting imbalances of baseline characterisics
      between the treatment groups by the propensity score, the odds ratio was 2.274,
      demonstrating a significant superiority (p<0.001) of Contractubex treatment as
      compared to corticosteroid treatment. The time to normalization of erythema,
      pruritus and consistency was significantly (p=0.034) shorter with Contractubex
      treatment (median 344 days) than with corticosteroids (median 507 days). No
      unexpected or severe adverse events occurred in the Contractubex-treated
      patients. Apart from moderate pruritus (10% Contractubex vs. 1% corticosteroids),
      adverse events were significantly (p<0.001) more frequent in corticosteroid
      treated patients (teleangiectasias 15% vs. 7% Contractubex; cutaneous atrophy of
      scars 10% vs. 2% Contractubex; cutaneous atrophy of scar surrounding skin tissue
      11% vs. 1% Contractubex). CONCLUSION: For the primary aim of this study
      (assessment of normalization of erythema, pruritus, and consistency of
      hypertrophic scars) and for time to normalization, local administration of
      Contractubex was significantly more effective than corticosteroid treatment.
      Concerning safety, Contractubex treatment was associated with significantly less
      adverse events (e.g. teleangiectasias, cutaneous atrophy of scars and surrounding
      skin tissue) than topical corticosteroid application.

PMID- 16634532
TI  - Four problems with the clinical control of interstitial pneumonia, or chronic
      fatigue syndrome, using the megadose vitamin C infusion system with
      dehydroepiandrosterone-cortisol annex.
AB  - Since 1996 in our clinic, the regular practice of megadose vitamin C infusion
      with dehydroepiandrosterone-cortisol annex and the continuous intake of
      erythromycin and chloramphenicol have been found useful for the clinical control
      of the autoimmune disease interstitial pneumonia, also known as chronic fatigue
      syndrome. The long-term use of these two systems for the treatment of the
      autoimmune disease has led to the emergence of four problems of theoretical or
      practical importance, as described below: i) Should maintenance of the above core
      treatments be continued for prophylactic purposes in the absence of acute signs
      of pneumonia? Evidence indicated that their use was essential to arrest the
      dynamic activity of an intrapulmonary bacterial colony in the immunodeficient
      host, and that the 5-year survival rate of interstitial pneumonia patients would
      have been worse without the prophylactic practice of the 2 treatments. ii)
      Evidence was presented to suggest that the activity of the intrapulmonary
      bacterial colony was becoming less responsive because of the emergence of a drug
      resistent mutant bacterium. The introduction of new antibiotics (kanamycin) was
      found to improve the acute signs of pneumonia. iii) The bone marrow function of
      one male patient with interstitial pneumonia was found to decline during the
      observation period of 9 years. It was speculated that his bone marrow, like his
      lungs, was in the course of fibrosis. iv) One female patient was diagnosed with
      breast cancer in the course of interstitial pneumonia treatment--an example
      indicating that the persistence of an autoimmune disease in an elderly subject
      might be associated with the emergence of malignancy. Dehydroepiandrosterone was
      shown to promote the recovery of hepatic function in the course of cancer
      chemotherapy with cyclophosphamide. The beneficial effect of the adrenal androgen
      was dose-dependent. The significance of this finding is discussed in the light of
      the steroid carcinogenesis concept. The reasoning behind the view that
      interstitial pneumonia and chronic fatigue syndrome are one disease is also
      discussed.

PMID- 16634533
TI  - Interrelationship of hepatic function, thyroid activity and mood status in
      alcohol-dependent individuals.
AB  - BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the
      development of mood disorders such as depression and anxiety that almost
      invariably coexist in alcohol-dependent individuals. The aim of the present study
      was to investigate the severity of liver dysfunction and thyroid activity in
      correlation with anxiety and depressive-like symptomatology before and after a
      detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol
      abusing/dependent subjects treated on an in-patient basis according to a standard
      detoxification protocol, measurements of the serum levels of hepatic enzymes
      (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of
      anxiety, depression and global functioning were obtained at baseline and at
      weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the
      alcohol detoxification, most measurements returned to normal levels and
      correlations were observed between the levels of hepatic enzymes and thyroid
      hormones. Additionally, a significant correlation was obtained between the levels
      of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated
      a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence
      with possible implications in the diagnosis and treatment of mood disorders
      associated with alcohol abuse.

PMID- 16634534
TI  - Gemcitabine combined with 5-fluorouracil for the treatment of advanced carcinoma
      of the pancreas.
AB  - BACKGROUND: Gemcitabine is an active agent in pancreatic cancer, showing clinical
      synergy with 5-fluorouracil (5-FU). The aim of the study was to evaluate the
      safety and efficacy of the combination of gemcitabine and 5-FU in patients with
      advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-two patients
      (median age, 62 years), with advanced or metastatic pancreatic adenocarcinoma,
      were enrolled in the study. The combination of gemcitabine (1000 mg/m2) and 5-FU
      (600 mg/m2) was administered on days 1, 8 and 15 and repeated every 28 days.
      RESULTS: A total of 168 cycles (median 4 cycles per patient) were administered.
      Partial responses were observed in 6 patients (14.2%) and stable disease in 11
      (26.2%). The overall clinical benefit was 40.4%. Symptom relief and improvement
      of performance status were observed in 18 (42.8%) patients. The median time to
      progression, median duration of response and the median overall survival, were 6,
      7 and 13 months, respectively. The most common grade 3 to 4 toxicities were
      neutropenia, anaemia and diarrhoea. CONCLUSION: The combination of gemcitabine
      and 5-FU is an active regimen for the treatment of advanced pancreatic cancer
      with an acceptable toxicity profile.

PMID- 16634535
TI  - The relationship between tissue RBC n-3 fatty acids and pulse wave velocity.
AB  - Consumption of n-3 fatty acids is well-known to prevent deaths from coronary
      heart disease. However, not many studies have investigated the effects of n-3
      fatty acids on arteriosclerosis in free living subjects. The pulse wave velocity
      between the brachia and ankles (baPWV) of 161 healthy male subjects was measured
      and the fatty acid composition of the total phospholipid fraction of their red
      blood cells (RBC) analyzed. There was a significant inverse correlation between
      the eicosapentaenoic acid concentrations in the RBC phospholipid fraction and
      baPWV of the subjects after adjustment for age, pulse rate and diastolic
      pressure, or further for body mass index, smoking status, diabetes and the ratio
      of low-density cholesterol to high-density cholesterol. Although baPWV values may
      not directly indicate arteriosclerosis, the present study suggests that long-term
      n-3 fatty acid intake is beneficial for the vascular system.

PMID- 16634536
TI  - Combined mucormycosis and Aspergillosis of the rhinocerebral region.
AB  - BACKGROUND: Opportunistic fungal infections are rare, life-threatening conditions
      and are a major cause of morbidity and mortality in immunocompromised hosts. Our
      experience in the management of a case of combined mucormycosis and aspergillosis
      of the rhinocerebral region is presented. PATIENTS AND METHODS: The infection
      developed a few weeks after tooth extraction, massively involving facial
      structures. After diagnosis, the patient underwent prolonged combined systemic
      antifungal treatment. Once the local and general conditions had stabilized, an
      extensive surgical debridement was performed, followed by reconstruction with a
      pedicled myocutaneous flap. RESULTS: This approach was curative with patient
      survival after 16 months. CONCLUSION: Early diagnosis, early anti-fungal
      treatment and early stabilization of the patients' general condition are
      fundamental for patient survival. Surgery is necessary for fungal eradication,
      but must be performed according to the above conditions. Pedicled muscle flaps
      are considered the first reconstruction choice because of their excellent blood
      perfusion and resistance to fungal invasion.

PMID- 16634537
TI  - [A case of takotsubo cardiomyopathy provoked by taking a new quinolone antibiotic
      drug and a non-steroidal anti-inflammatory drug].
AB  - A 97-year-old woman was provoked a convulsion after taking a new quinolone
      antibiotic drug Levofloxacin and a non-steroidal anti-inflammatory drug
      Loxoprofen. At a later time, she was suffered from severe chest pain. An
      electrocardiogram showed ST segment elevation in leads II, III and aVF, and T
      wave inversion in leads V1 to V4. Coronary angiography demonstrated no organic
      stenosis, however biventriculography revealed apical ballooning akinesis and
      basal hyperkinesis. Positron emission tomography was also performed to assess the
      uptake of 18F-fluorodeoxyglucose (FDG) after 75 g oral glucose loading for
      evaluating myocardial glucose metabolism at 10th day. Severely reduced uptake of
      FDG was observed in the apical ballooning region. Left ventriculography showed
      normal wall motion at 19th day. Thallium-201 myocardial single-photon emission
      computed tomography (SPECT) to determine the status of myocardial perfusion at
      the 20th hospital day showed normal perfusion. Iodine-123-beta-methyl-p
      iodophenyl penta-decanoic acid myocardial SPECT to evaluate myocardial fatty acid
      metabolism at the 23rd day revealed severely reduced uptake in the apical
      ballooning region. These findings suggested that the coronary microcirculation
      was impaired in the apical ballooning region.

PMID- 16634538
TI  - [Clinical usefulness of 1231I-BMIPP myocardial SPECT in patient with
      microvascular spasm: a case report].
AB  - This patient was a 64-year-old man with chest pain at rest. An electrocardiogram
      showed depression of the ST segment in V2-V5 leads during chest pain. 123I-BMIPP
      myocardial SPECT revealed reduced uptake in the apex. Coronary angiographies
      revealed severely delayed filling of contrast medium without narrowing of
      epicardial coronary arteries. An intracoronary infusion of isosorbide dinitrate
      did not improve the delayed filling of contrast medium or the ST segment
      depression. After an intracoronary infusion of nicorandil, coronary arterial
      flows were remarkably improved, chest symptoms disappeared, and
      electrocardiographic findings were improved. Left ventriculography showed severe
      hypokinesis in the apex. After the medication with nicorandil, reduced 123I-BMIPP
      myocardial uptake and reduced wall motion on echocardiography were improved.
      These findings suggest that myocardial ischemia in this case might be explained
      as having been caused by microcirculation disturbance.

PMID- 16634539
TI  - [Safety of adenosine stress myocardial perfusion imaging by a one-route infusion
      protocol].
AB  - When adenosine stress testing is performed, a vein is generally accessed in each
      arm. To determine whether the one-route infusion protocol, that is, infusion via
      one upper arm vein, is safe, myocardial perfusion imaging was performed during
      adenosine stress testing in patients with angina pectoris. Sixty-six consecutive
      patients (43 men, 68 +/- 11 years of age) with suspected coronary artery disease
      were enrolled in this study. For the stress test, adenosine was injected at 120
      microg/kg/min for 6 minutes. Systolic blood pressure, diastolic blood pressure,
      and heart rate did not show any significant changes after injection of the
      adenosine and radioisotope (RI) tracer. Adverse events during infusion of the
      adenosine were seen in 42 (64%) patients and included chest discomfort/oppression
      in 17 (26%) and dyspnea/throat discomfort in 15 (23%). On the other hand, adverse
      events just after infusion of the RI tracer occurred in 5 (8%) patients and
      included chest oppression in 2 (3%) and dyspnea in 1 (2%). Almost all adverse
      events disappeared quickly without treatment. Therefore, we concluded that
      adenosine stress myocardial perfusion imaging using a one-route infusion protocol
      is safe and useful to do for patients unable to secure veins in both arms.

PMID- 16634540
TI  - [The 27th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (the
      30th survey in 2004)].
AB  - This survey was performed in order to investigate the incidence of adverse
      reactions to radiopharmaceuticals and defect products in FY2004 in Japan. It was
      based on responses to questionnaires sent to nuclear medicine institutions. The
      reply was obtained from 968 institutions among 1,220 to which the questionnaire
      had been sent. Sixteen cases of adverse reactions were reported. A total of
      1,277,906 radiopharmaceutical administrations was reported. The incidence of
      adverse reactions per 100,000 cases was 1.3. Eight cases of defect products were
      reported, and the incidence of defect products per 100,000 cases was 0.6.

PMID- 16634541
TI  - [The effect of isoflurane anesthesia on dopamine release in rat striatum with
      pretreatment of imipramine].
AB  - BACKGROUND: Isoflurane anesthesia has been shown to have a possibility of
      inducing a biphasic effect on dopamine release in rat striatum. The current study
      investigated the effect of isoflurane on the extracellular concentration of
      dopamine in the rat striatum pretreated by a classical antidepressant,
      imipramine, using in vivo microdialysis techniques. METHODS: After
      intraperitoneal administration of 5 and 10 mg x kg(-10 of imipramine, the rats
      were anesthetized with 1 and 2.5% isoflurane inhalation. The control group was
      injected saline. Isoflurane anesthesia increased the extracellular concentration
      of dopamine metabolites without any change in dopamine concentration. RESULTS:
      Under pretreatment of 5 mg x kg(-1) of imipramine, the effect of isoflurane on
      the change in dopamine and its metabolites was preserved. Whereas, 10 mg x kg(-1)
      of imipramine pretreatment induced a marked increase in the extracellular
      concentration of dopamine when only 1% isoflurane was applied but not with 2.5%
      isoflurane. In the rat administered 10 mg x kg(-1) of imipramine, anesthesia
      induced increase of 3-methoxytyramine was not found. CONCLUSIONS: Our previous
      investigation suggested that the isoflurane anesthesia has a biphasic effect on
      dopamine release in rat striatum under pargyline pretreatment. The same effect
      was shown in the rat administered imipramine. Isoflurane anesthesia might modify
      dopaminergic neural activity and release of neurotransmitters through different
      and complex ways.

PMID- 16634542
TI  - [Neuromuscular blocking effects, pharmacokinetics and safety of Org 9426
      (rocuronium bromide) in Japanese patients].
AB  - BACKGROUND: The purpose of this study was to examine pharmacodynamics,
      pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese
      patients. METHODS: Seventy-eight patients anesthetized with thiopental,
      droperidol, fentanyl and nitrous oxide, were randomized to receive either a
      single dose of Org 9426 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1).
      Contraction of the adductor pollicis to the ulnar nerve stimulation (0.1 Hz) was
      measured by acceleromyography. Blood was sampled over 6 hr and pharmacokinetic
      variables were calculated by plasma concentrations of Org 9426. RESULTS: Onset
      times for patients receiving 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1)
      were 271.5 s, 140.0s and 125.4s, respectively. There was a dose-dependent
      increase in clinical durations until 25% recovery of twitch height (17.4 min in
      0.3 mg x kg(-1) group, 37.2 min in 0.6 mg x kg(-1) and 60.4 min in 0.9 mg x kg(
      1) group). Pharmacokinetic study revealed that elimination half life, steady
      state volume of distribution and plasma clearance of Org 9426 were 48-76 min, 146
      181 ml x kg(-1), and 3.8-4.5 ml x min(-1) x kg(-1), respectively. No adverse
      effects were found except a case of local erythema on a forearm. CONCLUSIONS: The
      efficacy of neuromuscular block, stable pharmacokinetic behavior and excellent
      safety of Org 9426 were also confirmed in Japanese surgical patients.

PMID- 16634543
TI  - [Postoperative patient-controlled analgegia using intravenous pentazocine].
AB  - BACKGROUND: Pentazocine is one of the most popular analgesics for postoperative
      analgesia in Japan. For patient-controlled analgesia (PCA), however, opioid
      agonists are used commonly, and little information is available concerning PCA by
      pentazocine. We studied the effects of postoperative PCA using intravenous
      pentazocine. METHODS: Eighteen male patients who had undergone open reduction and
      internal fixation of fructure of extremities under general anesthesia received
      intravenous pentazocine via PCA. The procedure of PCA was as follows; continuous
      infusion set 1.5-2.5 mg x h(-1), size of bolus set 5-10 mg with 10-15 minutes
      lockout interval. We added droperidol for prevention of nausea and vomiting.
      RESULTS: Eleven patients (61.1%) recovered without using any other analgesics.
      However, seven patients needed other treatments. Six patients used suppository of
      diclofenac and the other one received pentazocine intramuscularly besides
      diclofenac. Four of seven patients received these additional analgesics without
      PCA bolus. No significant complications were observed except nausea in three
      patients, drowsiness in two and somnolence in one. CONCLUSIONS: Our program of
      PCA was safe and effective for postoperative analgesia. But the guidance for
      patients, surgeons and nursing staff is important using PCA therapy more
      effectively.

PMID- 16634544
TI  - [Prophylactic strategies for perioperative pulmonary embolism: the second report;
      reevaluation of usefulness of combination of elastic stockings and intermittent
      pneumatic compression].
AB  - BACKGROUND: The incidence of perioperative pulmonary thromboembolism (PTE) has
      increased in Japan. As the mortality rate of PE is very high, its prophylaxis is
      important. METHODS: From January 1998 to December 1999 no prophylactic strategies
      were employed. From May 2000 to December 2004, elastic stockings (ES) for
      prevention of perioperative deep vein thrombosis were worn from the morning of
      the operation until the beginning of ambulation. Intermittent pneumatic
      compression (IPC) apparatuses were used in combination with ES right after the
      induction of anesthesia until leaving ICU. Sixty percent of patients stayed in
      ICU until the next morning after the operation and the other patients for a few
      hours after the end of surgery. RESULTS: We managed 4,511 patients without any
      preventing method and 11,688 patients with the combination of ES and IPC. Seven
      patients developed PTE without any prophylaxis and one with preventative methods.
      The incidence of PTE was significantly decreased from 15.51 persons/10,000 cases
      to 0.86 person/10,000 cases. Symptomatic deep vein thrombosis occurred in 3 cases
      in spite of preventative methods. CONCLUSIONS: Our preventive strategies with the
      combination of ES and IPC seem to be useful to decrease the incidence and
      severity of perioperative PTE.

PMID- 16634545
TI  - [The heart rate variability in mice: telemetric evaluation of endotoxin shock].
AB  - BACKGROUND: Recently, the knowledge regarding all types of shock has increased.
      In the critical period, the maintenance of perfusion to important organs and of
      autonomic cardiovascular control is a clue to improve outcome. The current
      investigation studied the effects of endotoxin shock on the heart rate
      variability (HRV), which might be an early marker of multiple organ dysfunction
      syntion. METHODS: CL 57 BL/6 J mice (30-32 g) were implanted with intra-abdominal
      telemetry transmitters and data collection began 7 days after surgery and
      continued for 5 hours after the treatment. In endotoxin group, 3 mg x kg(-1) of
      E. coli lipopylysaccharide (0127 : B 8) was administered intraperitoneally and
      the same dose of saline was administered in control group. From the beat-by-beat
      values, heart rate (HR), standard deviation and coefficients of variation (RMSSD)
      were calculated. Integrated values of power spectral density were derived by
      summing depending on the frequency ranges, which were chosen with respect to the
      results of the previous investigation as follows: very low frequency (VLF) < 0.15
      Hz; low frequency (LF), 0.15-1.5 Hz; and high frequency (HF), 1.5-5.0 Hz.
      RESULTS: HR showed no difference between the groups. RMSSD, Total Power, VLF, LF
      and HF increased in control group throughout the experiments, but, decreased in
      endotoxin group even 5 hr after the treatment. CONCLUSIONS: There has been scarce
      information on mice HRV, but we have demonstrated that endotoxin administration
      significantly decreases RMSSD and spectral density at low and high frequencies.

PMID- 16634546
TI  - [Anesthetic management for a patient with severely obstructed upper airway
      undergoing CO2 laser resection of the tracheal tumor].
AB  - A 76-year-old woman was scheduled to undergo a laser resection of the tracheal
      tumor which severely obstructed the upper airway. She had a past history of
      thoracic aortic aneurysm resection and myocardial infarction. After spraying the
      patient's oral cavity with 8% lidocaine, a laryngeal mask airway was inserted
      under spontaneous respiration. Tumor resection was successfully performed using
      CO2 laser through the laryngeal mask airway with the aid of low dose fentanyl
      under spontaneous respiration. Maintaining FIO2 at 0.5 could prevent hypoxemia.
      Although mild edema was observed in the larynx at the completion of the surgery,
      the patient achieved remarkable improvement in her breathing status.
      Consequently, she was able to undergo radiotherapy on the 5th postoperative day.
      This effectively reduced the tumor volume.

PMID- 16634547
TI  - [Taste loss following the use of the laryngeal mask airway].
AB  - The laryngeal mask airway can be used safely to manage the airway. However, it is
      associated with a few complications. We report a case of taste loss following the
      use of the laryngeal mask airway in a 20-year-old man. He was scheduled for open
      reduction and internal fixation of fractured bones. Anesthesia was induced with
      propofol and maintained with nitrous oxide, oxygen and sevoflurane. The patient
      complained of loss of taste on the first postoperative day. Taste loss lasted for
      six months. We conclude that loss of taste was caused by lingual nerve injury
      associated with malposition of the laryngeal mask airway.

PMID- 16634548
TI  - [Intraoperative anaphylactic shock induced by methylergometrine and oxytocin].
AB  - We report a case of intraoperative anaphylactic shock in a 32-year-old
      multigravida woman undergoing elective cesarean section for partial placenta
      previa. Anesthesia was performed using combined spinal and epidural technique.
      After the baby was born, methylergometrine was administered i.v. simultaneously
      with oxytocin, the latter injected directly into the uterine muscle by an
      obstetrician. Several minutes later, she presented with dyspnea and became
      agitated. Because of the potential risk of pulmonary embolism, the patient was
      immediately intubated and mechanical ventilation was started. Her systolic blood
      pressure decreased to 50 mmHg and SpO2 to 87% under 100% oxygen administration.
      After catecholamine infusion, however, her respiratory condition soon improved.
      Postoperatively, her conjunctiva and vulva were not edematous. From the clinical
      course, it was considered that the patient was very likely to have suffered an
      anaphylactic reaction to oxytocin or methylergometrine. Forty days later,
      serological examinations as well as skin tests for those two drugs were carried
      out. While the serological tests were negative, the skin tests indicated the
      patient was allergic to both drugs. It is concluded that the endogenous peptide
      oxytocin can induce anaphylactic shock in multiparous women.

PMID- 16634549
TI  - [Insertion of a laryngeal mask airway before removal of a nasotracheal tube in a
      patient after anterior spine surgery].
AB  - A 19-year-old man with cervical spondylosis (C4-C6) was scheduled for an anterior
      spine surgery. Anesthesia was induced with propofol and fentanyl, and
      nasotracheal intubation was performed without difficulty after vecuronium
      administration. Anesthesia was maintained with sevoflurane and nitrous oxide in
      oxygen supplemented with fentanyl. No complications were observed during the
      operation. After surgery, the patient's head and neck were stabilized by a halo
      vest, and we attempted to minimize stress responses associated with tracheal
      extubation. While the patient was still deeply anesthetized, and the nasotracheal
      tube was in place, a laryngeal mask airway (LMA) was placed without difficulty.
      After confirming correct position of the LMA, the nasotracheal tube was removed
      without body movement or coughing. Removal of the LMA was safely performed after
      recovery of the patient's respiration and consciousness. We believe that the
      laryngeal mask airway is useful during emergence from anesthesia in the patient
      whose trachea is intubated nasally.

PMID- 16634550
TI  - [Anesthetic management of an infant with Cornelia de Lange syndrome].
AB  - We report anesthetic management of an infant with Cornelia de Lange syndrome. A
      12-month-old girl with Cornelia de Lange syndrome was scheduled for
      ureterocystoneostomy because of vesicoureteral reflux. Preoperative physical
      examination suggested difficult tracheal intubation. After induction of
      anesthesia with sevoflurane (5%) in nitrous oxide (70%) and oxygen, a laryngeal
      mask airway (# 1.5) was inserted. A guide wire was inserted in the trachea
      through a laryngeal mask airway under direct vision of a fiberoptic bronchoscope.
      A tube-exchanger stylet was inserted around the guide wire after the laryngeal
      mask airway and fiberoptic bronchoscope had been removed. An endotracheal tube
      (ID 4.0 mm) was easily intubated around the tube-exchanger stylet. During the
      surgery, anesthesia was maintained with sevoflurane (2-3%) in nitrous oxide (50%)
      and oxygen. There was no perioperative pulmonary complication.

PMID- 16634551
TI  - [A case of general anesthesia combined with epidural anesthesia in a pregnant
      woman undergoing laparoscopic cholecystectomy].
AB  - We report a case of general anesthesia for laparoscopic cholecystectomy at 12
      weeks of gestation. A 20-year-old woman weighing 123 kg was admitted with
      epigastralgia. She was diagnosed as pregnancy of 6 weeks of gestation and acute
      cholecystitis. Percutaneous trans-gallbladder drainage was performed to delay
      operation until 12 weeks of gestation. Laparoscopic cholecystectomy was performed
      uneventfully under general anesthesia combined with epidural anesthesia. There
      were no clinical signs of fetal distress during the perioperative period.

PMID- 16634552
TI  - [Intraoperative cardiac arrest due to coronary vasospasm after tourniquet release
      -a case report].
AB  - A 55-year-old man with no past history of ischemic heart disease underwent open
      reduction and internal fixation of the right arm because of an open fracture.
      Under general anesthesia with brachial plexus block, the operation was started
      after the upper arm had been pressurized at 280 mmHg by tourniquet. The patient
      had cardiac arrest 15 min after the tourniquet release, and was resuscitated by
      CPR. Postoperative intracoronary infusion of acetylcholine revealed that the
      coronary artery is sensitive to the agent, indicating that the intraoperative
      cardiac arrest might have been due to coronary vasospasm. Although the similar
      case is rare, attention should be taken during the anesthetic management with the
      use of tourniquet.

PMID- 16634553
TI  - [Airway obstruction caused by massive swelling of the tongue following bilateral
      tonsillectomy for sleep apnea syndrome].
AB  - A case of airway obstruction caused by the tongue swelling is reported. The
      patient is a 5-year-old boy scheduled for bilateral tonsillectomy for sleep apnea
      syndrome. Anesthesia was slowly induced by sevoflurane and maintained with
      nitrous oxide, fentanyl and sevoflurane. Bilateral tonsillectomy and
      adenoidectomy were performed uneventfully under general anesthesia. The operation
      time was 2 hours and 30 minutes. Following the surgical procedure, the
      endotracheal tube was removed. Shortly after the extubation, the patient
      complained of difficult articulation and paradoxical respiration. Trachea was
      intubated immediately. Oxygen saturation was within normal limits throughout all
      the procedures. Swelling of the tongue was aggravated and was not relieved by
      steroid infusion. Massive swelling of the face and neck was observed on the next
      day. CT scan and fiberoptic scope examination showed the swollen tongue
      obstructing the upper airway. Additional administration of steroid was continued.
      On the third postoperative day, edema was relieved and the endotracheal tube was
      removed. Clinical course after the extubation was uneventful. No laboratory data
      was obtained suggesting the allergic basis. Extubation should be performed
      carefully and respiratory condition should be observed cautiously following the
      oral surgery of even a short duration.

PMID- 16634554
TI  - [The combined use of laryngoscope and Trachlight: another option for endotracheal
      intubation in patients with large epiglottic cysts].
AB  - Epiglottic cysts often cause difficulty in airway management. A 71-year-old man
      had extraction for an epiglottic cyst of 4 cm in diameter. Anesthesia was induced
      with small divided doses of propofol. After verifying that mask ventilation was
      possible under light anesthesia, vecuronium was used for muscle relaxation.
      Because of the size of the cyst, it was impossible to observe directly the larynx
      using a laryngoscope. Therefore, while moving the tongue to the left with the
      laryngoscope, an endotracheal tube was inserted into the trachea using the
      Trachlight. The operation was finished in 55-min and the patient was extubated 15
      min after the end of the operation. His postoperative course was uneventful and
      he was discharged from the hospital three days after the operation. The authors
      conclude that the combined use of the laryngoscope and Trachlight is helpful for
      endotracheal intubation in patients with large epiglottic cysts.

PMID- 16634555
TI  - [A case of a pediatric patient with tuberous sclerosis (Bourneville-Pringle
      disease) and frequent epileptic seizure for intensive dental treatment under
      general anesthesia].
AB  - Tuberous sclerosis (Bourneville-Pringle disease) is a rare disease with a triad
      of mental retardation, epilepsy, and facial spot. Management of the patients with
      tuberous sclerosis under general anesthesia has been previously reported.
      However, there are few case reports about management under general anesthesia of
      a pediatric patient with tuberous sclerosis with frequent epileptic seizure.
      Here, we report a case of a pediatric patient with tuberous sclerosis and
      frequent epileptic seizure who underwent intensive dental treatment under general
      anesthesia with careful management of epilepsy. The patient was discharged on the
      day of surgery without any complications. In this case report, we discussed the
      appropriate assessment of the complications of tuberous sclerosis; such as, of
      central nervous, circulatory, respiratory, endocrine, and urinary systems
      including the management of general anesthesia.

PMID- 16634556
TI  - [Bronchial blocking with a balloon wedge pressure Catheter in a small infant].
AB  - The need for one-lung ventilation has been increasing even in pediatric patients.
      However, the trachea is so narrow in pediatric patients that ordinary double
      lumen tubes can not be used and there have been many reports on devices or
      measures to block one lung. We report our experience with a female infant
      weighing 2 kg who had severe chronic lung disease under mechanical ventilation,
      and underwent left lung lower lobectomy with one-lung ventilation technique. We
      chose a balloon wedge pressure catheter to block the left main bronchus, because
      it has a central lumen through which a guide wire can be passed and sucking is
      available. The infant was in need of continuous ventilation and the catheter was
      too soft to be inserted directly. We first inserted an 18G catheter of a needle
      catheter assemble outside the tracheal tube through which a guide wire was
      inserted into the left main bronchus with the aid of direct vision of a 2-mm
      fiberoptic bronchoscope through the tracheal tube, and then inserted the balloon
      wedge pressure catheter placing it in an appropriate position. One-lung
      ventilation was successfully achieved and the operative and postoperative course
      was uneventful.

PMID- 16634557
TI  - [Outline and effectiveness of support system in the surgical center by supply,
      processing and distribution center (SPD)].
AB  - Supply, Processing and Distribution system had been introduced to surgical center
      (the University of Tokyo Hospital) since October of 2002. This system had reduced
      stock for medicine and materials and decreased medical cost dramatically. We
      designed some kits for therapeutic drugs related to anesthesia. They were
      prepared for general anesthesia, epidural and spinal anesthesia, and
      cardiovascular anesthesia, respectively. One kit had been used for one patient,
      and new kits were prepared in the anesthesia preparation room by pharmaceutical
      department staffs. Equipment, for general anesthesia as well as epidural and
      spinal anesthesia, and central catheter set were also designed and provided for
      each patient by SPD system. According to the questionnaire of anesthesia
      residents before and after introduction of SPD system, the time spent for
      anesthesia preparation had been reduced and 92.3% residents had answered that
      preparation for anesthesia on the previous day was getting easier. Most of the
      anesthesia residents had been less stressed after introduction of SPD system.
      Beside the dramatic economical effect, coordination with SPD system and
      pharmaceutical department reduced anesthesia preparation time and stress of the
      staff. Introduction of Support system of SPD to surgical center is important for
      safe and effective management of operating rooms.

PMID- 16634558
TI  - [A Kumamoto model of clinical training in tracheal intubation for paramedics].
AB  - BACKGROUND: Since July 2004, the Japanese Ministry of Health, Labor and Welfare
      approved certified paramedics to perform emergency prehospital tracheal
      intubation. A specialized training system in tracheal intubation has been
      established in Kumamoto Prefecture. METHODS: The Kumamoto Prefectural Medical
      Control Organization, a tracheal intubation task force was established:
      consisting of the departments of Anesthesiology at Kumamoto University and 11
      other major hospitals, along with Kumamoto Prefecture and the 14 prefectural fire
      departments. This group published the Kumamoto training guidelines and a training
      system for paramedics. RESULTS: Kumamoto Prefecture appealed for support of
      paramedic activity on television and in newspapers as public education. The
      prefectural governor officially asked hospitals to train paramedics. Because 9 of
      the 14 fire-departments had no regional teaching hospital, trainees were matched
      with other hospitals by the task force. The task force published a pamphlet to
      inform surgical patients about tracheal intubation training and to recruit
      patients as practice volunteers. Anesthesiologists undertook significant roles in
      making arrangements to facilitate the project at their hospitals, in addition to
      teaching paramedics prior to surgical procedures. CONCLUSIONS: The Medical
      Control Organization, Kumamoto Prefecture, anesthesiologists and emergency
      response personnel worked together successfully to promote the training program
      for clinical tracheal intubation by paramedics.

PMID- 16634559
TI  - [Newly developed BONFILS Retromolar Intubation Fiberscope for difficult airway].
AB  - Battery powered BONFILS Retromolar Intubation Fiberscope (BRIF) is a nonflexible
      fiberscope having the same curvature as the Macintosh laryngoscope for difficult
      airway. We used this device in two patients; A 65-year-old man with small chin
      and a 35-year-old man with neck spinal cord injury. Two trials of orotracheal
      intubation were accomplished easily in 20 seconds. We conclude that BRIF is
      useful for orotracheal intubation in patients in whom neck extension is contra
      indicated.

PMID- 16634560
TI  - [Report of the 25th annual meeting of the Japanese Society for Clinical
      Anesthesia].

PMID- 16634561
TI  - [DNA damage response of WRN protein characterized by in situ analysis].

PMID- 16634562
TI  - [Insulin-like signal regulating the life span of the animals].

PMID- 16634563
TI  - [Shc signaling in longevity control and neuroprotection].

PMID- 16634564
TI  - [Aging and age-related diseases caused by superoxide anion production from
      mitochondria].

PMID- 16634565
TI  - [Pathogenesis of metabolic syndrome].

PMID- 16634566
TI  - [DNA helicases and progeroid syndromes].

PMID- 16634567
TI  - [Telomere and telomerase in age related diseases].

PMID- 16634568
TI  - [Molecular analysis for the role of human parvovirus B19 infection in rheumatoid
      arthritis].

PMID- 16634569
TI  - [Regulatory mechanisms of osteoclast development and bone disorders].

PMID- 16634570
TI  - [Role of estrogen in aging and aging-related diseases].

PMID- 16634571
TI  - [Bridges between brain-informatics and brain aging].

PMID- 16634572
TI  - Highly active titanium-based olefin polymerization catalysts supported by
      bidentate phenoxyamide ligands.
AB  - Phenoxyamide complexes of Ti-containing 2,6-X2C6H3 (X = Cl, Br) substituents,
      when activated by methyl aluminoxane, afford catalysts with very high activities
      for the polymerization of ethylene and with good incorporation of 1-hexene.

PMID- 16634573
TI  - New cuprates featuring ladderlike periodic arrays of [Cu3O8]10- trimeric magnetic
      nanostructures.
AB  - A new family of cuprates, Li2Cu3(SiO3)4 (1) and Na2Cu3(GeO3)4 (2), was isolated
      in molten salt media. The extended lattices contain ladderlike periodic arrays of
      [Cu3O8]10- magnetic nanostructures. Magnetic properties of the Na2Cu3Ge(4
      x)SixO12 series, where x = 0, 0.86, and 1.72, were systematically studied. The
      geometrically induced magnetic couplings are tunable upon cation substitution.

PMID- 16634574
TI  - Manganese complexes of 1,3,5-triaza-7-phosphaadamantane (PTA): the first nitrogen
      bound transition-metal complex of PTA.
AB  - The structures of two manganese(II) complexes of 1,3,5-triaza-7-phosphaadamantane
      (PTA) reveal the first transition-metal complexes of PTA in which the metal
      preferentially coordinates to a nitrogen and not the phosphorus of PTA. The
      coordination environment about the manganese was probed using X-ray
      crystallography (solid state) and EXAFS spectroscopy (solution).

PMID- 16634575
TI  - Pyrazolate-bridging dinucleating ligands containing hydrogen-bond donors:
      synthesis and structure of their cobalt analogues.
AB  - Convergent preparative routes to new urea-pyrazolate dinucleating ligands are
      described. Metal complexes of these ligands have hydrogen bond donors that are
      proximal to the metal centers that interact with other coordinated species. This
      is exemplified by Co(II) dimers with Co(II)-mu-Cl-Co(II) motifs, in which the
      chloro ligand is involved in four intramolecular hydrogen bonds. These
      noncovalent interactions appear to influence the Co(II)-Cl bonds, which are
      unusually long, having lengths greater than 2.5 A.

PMID- 16634576
TI  - Assembly of a heterobinuclear 2-D network: a rare example of endo- and exocyclic
      coordination of Pd(II)/Ag(I) in a single macrocycle.
AB  - The S3O2 macrocycle L1 was synthesized by a dithiol-dihalide coupling reaction
      under high-dilution conditions. The reaction of L1 with K2PdCl4 afforded an
      exocoordinated complex 1, [cis-Cl2Pd(L1)], which can then be manipulated to
      provide a heterobinuclear complex 3, {[Pd(L1)Ag(NO3)(2.5)](NO3)(0.5)}n, utilizing
      endocyclic Pd(II) and exocyclic Ag(I) in a single macrocycle through a successive
      reaction with AgNO3. The network of 3 contains a unique honeycomb-like 2-D sheet
      made up of the repeating unit [Ag6(NO3)6].

PMID- 16634577
TI  - Synthesis and structure of the bilayer hydrate Na0.3NiO2.1.3D2O.
AB  - The metal oxide bilayer deuterate (hydrate) Na(0.3)NiO2.1.3D2O
      (Na(0.3)NiO2.1.3H2O) were prepared from NaxNiO2 by extracting Na+ cations and
      simultaneously intercalating fully and nondeuterated water. High-resolution
      neutron powder diffraction, thermogravimetric analysis, and inductively coupled
      plasma atomic emission spectroscopy were used to show that a Na(0.3)(D2O)(1.3)
      network separates layers of edge-sharing NiO6 octahedra.

PMID- 16634578
TI  - Large-scale fabrication of TiO2 hierarchical hollow spheres.
AB  - In this Communication, we report the fabrication of well-crystallized rutile
      phase TiO2 hollow spheres using potassium titanium oxalate as the precursor. The
      spheres exhibited unique three-dimensional hierarchical architectures and
      demonstrated a significantly improved photocatalytic performance. The synthetic
      strategy used in this process represents a general approach and therefore may
      contribute to the formation mechanisms of hollow nanostructures.

PMID- 16634579
TI  - Synthesis of boron-iodinated o-carborane derivatives. Water stability of the
      periodinated monoprotic salt.
AB  - Boron periodination of o-carborane has been achieved by taking account of the
      fact that B atoms in the cluster are of two types, i.e., those adjacent to both C
      atoms and the remainder. The high number of nonequivalent leaving groups opens
      the possibility through B-C coupling to materials with novel possibilities and to
      self-assembling due to the enhanced polarizability of the C-H bond. Periodination
      has accentuated the acidity of the carborane, and monoprotic salts are stable in
      water.

PMID- 16634580
TI  - Molecular and electronic structures of oxo-bis(benzene-1,2-dithiolato)chromate(V)
      monoanions. A combined experimental and density functional study.
AB  - Two oxo-bis(benzene-1,2-dithiolato)chromate(V) complexes, namely, [CrO(L(Bu))2]1-
      and [CrO(L(Me))2]1-, have been synthesized and studied by UV-vis, EPR, magnetic
      circular dichroism (MCD), and X-ray absorption spectroscopy and by X-ray
      crystallography; their electro- and magnetochemistries are reported. H2L(Bu)
      represents the pro-ligand 3,5-di-tert-butylbenzene-1,2-dithiol, and H2L(Me) is
      the corresponding 4-methyl-benzene-1,2-dithiol. A structural feature of interest
      for both the complexes is the folding of the dithiolate ligands about the S-S
      vector providing Cs symmetry to the complexes. Geometry optimizations using all
      electron density functional theory with scalar relativistic corrections at the
      second-order Douglas-Kroll-Hess (DKH2) and zeroth-order regular approximation
      (ZORA) levels result in excellent agreement with the experimentally determined
      structures and electronic and S K-edge X-ray absorption spectra. From DFT
      calculations, the Cs instead of C2v symmetry for the complexes is attributed to
      the strong S(3p) --> Cr(3d(x2-y2)) pi-donation in Cs geometry providing
      additional stability to the complexes.

PMID- 16634581
TI  - Di- and trinuclear complexes derived from hexakis(2
      pyridyloxy)cyclotriphosphazene. Unusual P-O bond cleavage in the formation of
      [{(L'CuCl)2(Co(NO3)}Cl] (L' = N3P3(OC5H4N)5(O)).
AB  - Hexakis(2-pyridyloxy)cyclotriphosphazene (L) is an efficient multisite
      coordination ligand which binds with transition metal ions to produce dinuclear
      (homo- and heterometallic) complexes [L(CuCl)(CoCl3)], [L(CuCl)(ZnCl3)],
      [L(CoCl)(ZnCl3)], and [L(ZnCl2)2]. In these dinuclear derivatives the
      cyclophosphazene ligand utilizes from five to six nitrogen coordination sites out
      of the maximum of nine available sites. Further, the spacer oxygen that separates
      the pyridyl moiety from the cyclophosphazene ring ensures minimum steric strain
      to the cyclophosphazene ring upon coordination. This is reflected in the near
      planarity of the cyclophosphazene ring in all the dinuclear derivatives. In the
      dinuclear heterobimetallic derivatives one of the metal ions [Cu(II) or Co(II)]
      is hexacoordinate and is bound by the cyclophosphazene in a eta5-gem-N5 mode. The
      other metal ion in these heterobimetallic derivatives [Co(II) or Zn(II)] is
      tetracoordinate and is bound in an eta(1)-N(1) fashion. In the homobimetallic
      derivative, [L(ZnCl2)2], one of the zinc ions is five-coordinate (eta3-nongem
      N3), while the other zinc ion is tetracoordinate(eta2-gem-N2). The reaction of L
      with CuCl2 followed by Co(NO3)2.6H2O yields a trinuclear heterobimetallic complex
      [{(L'CuCl)2Co(NO3)}Cl] [L' = N3P3(OC5H4N)5(O)]. In the formation of this compound
      an unusual P-O bond cleavage involving one of the phosphorus-pyridyloxy bonds is
      observed. The molecular structure of [{(L'CuCl)2Co(NO3)}Cl] [L' =
      N3P3(OC5H4N)5(O)] reveals that each of the two the P-O-cleaved L' ligands is
      involved in binding to Cu(II) to generate the motif L'CuCl. Two such units are
      bridged by a Co(II) ion. The coordination environment around the bridging Co(II)
      ion contains four oxygen (two P-O units, one chelating nitrate) and two nitrogen
      atoms (pyridyloxy nitrogens).

PMID- 16634582
TI  - NMR and EPR studies of chloroiron(III) tetraphenyl-chlorin and its complexes with
      imidazoles and pyridines of widely differing basicities.
AB  - The NMR and EPR spectra of two bisimidazole and three bispyridine complexes of
      tetraphenylchlorinatoiron(III), [(TPC)Fe(L)2]+ (L = Im-d4, 2-MeHIm, 4-Me2NPy, Py,
      and 4-CNPy), have been investigated. The full resonance assignments of the
      [(TPC)Fe(L)2]+ complexes of this study have been made from correlation
      spectroscopy (COSY) and nuclear Overhauser enhancement spectroscopy (NOESY)
      experiments and Amsterdam density functional (ADF) calculations. Unlike the
      [(OEC)Fe(L)2]+ complexes reported previously (Cai, S.; Lichtenberger, D. L.;
      Walker, F. A. Inorg. Chem. 2005, 44, 1890-1903), the NMR data for the
      [(TPC)Fe(L)2]+ complexes of this study indicate that the ground state is S = 1/2
      for each bisligand complex, whereas a higher spin state was present at NMR
      temperatures for the Py and 4-CNPy complexes of (OEC)Fe(III). The pyrrole-8,17
      and pyrroline-H of all [TPCFe(L)2]+ show large magnitude chemical shifts (hence
      indicating large spin density on the adjacent carbons that are part of the pi
      system), while pyrrole-12,13-CH2 and -7,18-CH2 protons show much smaller chemical
      shifts, as predicted by the spin densities obtained from ADF calculations. The
      magnitude of the chemical shifts decreases with decreasing donor ability of the
      substituted pyridine ligands, with the nonhindered imidazole ligand having
      slightly larger magnitude chemical shifts than the most basic pyridine, even
      though its basicity is significantly lower (4-Me2NPyH+ pKa = 9.7, H2Im+ pKa =
      6.65 (adjusted for the statistical factor of 2 protons)). The temperature
      dependence of the chemical shifts of all but the 4-Me2NPy bisligand complexes
      studied over the temperature range of the NMR investigations shows that they have
      mixed (dxy)2(dxz,dyz)3/(dxzdyz)4(dxy)1 electron configurations that cannot be
      resolved by temperature-dependent fitting of the proton chemical shifts, with an
      S = 3/2 excited state in each case that in most cases lies at more than kT at
      room temperature above the ground state. The observed pattern of chemical shifts
      of the 4-CNPy complex and analysis of the temperature dependence indicate that it
      has a pure (dxzdyz)4(dxy)1 ground state and that it is ruffled, because ruffling
      mixes the a(2u)(pi)-like orbital of the chlorin into the singly occupied
      molecular orbital (SOMO). This mixing accounts for the negative chemical shift of
      the pyrroline-H (-6.5 ppm at -40 degrees C) and thus the negative spin density at
      the pyrroline-alpha-carbons, but the mixing is not to the same extent as observed
      for [(TPC)Fe(t-BuNC)2]+, whose pyrroline-H chemical shift is -36 ppm at 25
      degrees C (Simonneaux, G.; Kobeissi, M. J. Chem. Soc., Dalton Trans. 2001, 1587
      1592). Peak assignments for high-spin (TPC)FeCl have been made by saturation
      transfer techniques that depend on chemical exchange between this complex and its
      bis-4-Me2NPy adduct.

PMID- 16634583
TI  - Titanium(III) trisamidotriazacyclononane: reactions with C60 and radicals.
AB  - The reaction of titanium trisamidotriazacyclononane, [Ti{N(Ph)SiMe2}3tacn] (1),
      with C60 led to the synthesis of [Ti{N(Ph)SiMe2}3tacn]C60 (2) in high yield.
      Treatment of 2 with PhCH2Br led to the formation of [Ti{N(Ph)SiMe2}3tacn]Br and
      the radical PhCH2C60 (3). The reaction of CH3I with 1 gives two products. One is
      [Ti{N(Ph)SiMe2}3tacn]I (4), which results from the oxidation of 1 by an I
      radical. The other product, 5, resulting from a multistep reaction scheme that
      involves redox and nucleophilic reactions, presents an imido ligand formed by
      ligand rearrangement upon C-N bond cleavage. In solution, an exchange process
      that corresponds to a reversible 1,3-silyl shift between two Ti-bonded N atoms
      leads to isomers 5a and 5b. This equilibrium transforms an imido (TiNPh) into an
      amido ligand (Ti{NPh}SiMe2CH2Ph) with concomitant generation of an anionic moiety
      in the originally neutral triazacyclononane ring. In solution, either 5a or 5b
      displays additional fluxional processes that consist of its corresponding
      racemization processes.

PMID- 16634584
TI  - Syntheses, crystal structures, and magnetic characterization of five new dimeric
      manganese(III) tetradentate Schiff base complexes exhibiting single-molecule
      magnet behavior.
AB  - Tetradentate Schiff base ligands H2L (H2saltmen, H2salen, H2-5-Brsalen, and H2
      3,5-Brsalen), derived from the condensation of the corresponding salicylaldehyde
      or its derivatives with 1,1,2,2-tetramethylethyldiamine or 1, 2-diaminoethane,
      reacted with Mn(III) acetate or perchlorate salts and sodium azide or sodium
      cyanate to produce five Mn(III) dimer complexes, [Mn(saltmen)(O2CCH3)]2.2CH3CO2H
      (1), [Mn(saltmen)(N3)]2 (2), [Mn(salen)(NCO)]2 (3), [Mn(3,5-Brsalen)(3,5
      Brsalicylaldehyde)]2 (4), and [Mn(5-Brsalen)(CH3OH)]2(ClO4)2 (5). These new
      complexes have been characterized by IR, elemental analyses, crystal structural
      analyses, and magnetic studies. Within these Mn(III) dimeric complexes, two
      Mn(III) ions are connected by phenolate oxygen atoms with acetate, azide,
      cyanate, a 3,5-Brsalicyladehyde anion, and a neutral methanol molecule as the
      axial ligands for complexes 1-5, respectively. Complexes 1-4 exhibit intradimer
      ferromagnetic exchange and display frequency dependence of ac magnetic
      susceptibility, possibly showing single-molecule-magnet (SMM) behavior. In
      contrast, complex 5 shows an intradimer antiferromagnetic coupling probably
      originating from the relatively shorter Mn-O distance, compared to those of
      complexes 1-4.

PMID- 16634585
TI  - Citrate, in collaboration with a guanidinium ion, as a generator of cubane-like
      complexes with a range of metal cations: synthesis, structures, and magnetic
      properties of [C(NH2)3]8[(M(II))4(cit)4].8H2O (M = Mg, Mn, Fe, Co, Ni, and Zn;
      cit = Citrate).
AB  - Aqueous reaction mixtures containing citric acid, guanidinium carbonate, and a
      range of metal cations (Mg2+, Mn2+, Fe2+, Co2+, Ni2+, and Zn2+) at room
      temperature give crystalline products of composition
      [C(NH2)3]8[(M(II))4(cit)4].8H2O (cit = citrate). In all cases, the crystals are
      suitable for single-crystal X-ray diffraction studies, which reveal that the
      compounds are isostructural (space group P4(2)/n; a approximately 16.2 A, and c
      approximately 11.5 A). As was intended, cubane-like [M4(cit)4]8- complex anions
      are present. The individual citrate units are chiral, but each cubane unit
      contains two of one hand and two of the other, related around an S4 axis. The
      cubane units are involved in no less than 40 H-bonding interactions with
      guanidinium cations and lattice water molecules. Detailed susceptibility and
      magnetization studies show that the intracluster magnetic coupling within the
      Mn(II), Fe(II), Co(II), and Ni(II) cubanes is very weak in all cases with J
      values of -0.82, -0.43, and -0.09 cm(-1) for the Mn, Fe, and Co species,
      respectively. A two-J model gave the best agreement with the susceptibility and
      high-field magnetization data for the Ni(II) case, over the whole temperature
      range studied, and the sign of the parameters, J12 = -0.3 cm(-1) and J13 = +2.97
      cm(-1), correlated with the two Ni-(mu3-O)-Ni angles observed in the cluster
      structure. All members of the 3d-block [M4(cit)4]8- family have spin ground
      states, ST, of zero, with the higher ST levels just a few reciprocal centimeters
      away in energy.

PMID- 16634586
TI  - Synthesis, molecular and electronic structure, and TDDFT and TDDFT-PCM study of
      the solvatochromic properties of (Me2Pipdt)Mo(CO)4 complex (Me2Pipdt = N,N'
      dimethylpiperazine-2,3-dithione).
AB  - The synthesis, spectroscopic, and structural characterization of the
      (Me2Pipdt)Mo(CO)4 complex (Me2Pipdt = N,N'-piperazine-2,3-dithione) are presented
      in this paper. The title complex crystallizes in the P2(1)/n space group with a =
      25.541(3) A, b = 10.3936(14) A, c = 10.9012(12) A, beta = 92.261(9) degrees , V =
      2891.6(6) A(3), and Z = 8. Gas- and solution-phase structural and electronic
      features of (Me2Pipdt)Mo(CO)4 and Me2Pipdt have been investigated using density
      functional theory. The molecular structure underscores the flexibility of the
      NC(S)C(S)N fragment in both the free ligand and the metal complex. On the basis
      of structural, spectroscopic, and theoretical results, the bidentate ligand in
      (Me2Pipdt)Mo(CO)4 is considered to be in the dithione, not dithiolate, form. Time
      dependent density functional theory has been used for the investigation of the
      excited states and solvatochromic properties of (Me2Pipdt)Mo(CO)4. The calculated
      vertical excitation energies in solution are consistent with the experimental
      data, showing that the metal-to-ligand charge-transfer transitions, in both the
      visible and UV regions, dominate over the ligand-based pi-pi transitions.

PMID- 16634587
TI  - Copper(II) hexaaza macrocyclic binuclear complexes obtained from the reaction of
      their copper(I) derivates and molecular dioxygen.
AB  - Density functional theory (DFT) calculations have been carried out for a series
      of Cu(I) complexes bearing N-hexadentate macrocyclic dinucleating ligands and for
      their corresponding peroxo species (1c-8c) generated by their interaction with
      molecular O2. For complexes 1c-7c, it has been found that the side-on
      peroxodicopper(II) is the favored structure with regard to the bis(mu
      oxo)dicopper(III). For those complexes, the singlet state has also been shown to
      be more stable than the triplet state. In the case of 8c, the most favored
      structure is the trans-1,2-peroxodicopper(II) because of the para substitution
      and the steric encumbrance produced by the methylation of the N atoms. Cu(II)
      complexes 4e, 5e, and 8e have been obtained by O2 oxidation of their
      corresponding Cu(I) complexes and structurally and magnetically characterized. X
      ray single-crystal structures for those complexes have been solved, and they show
      three completely different types of Cu(II)2 structures: (a) For 4e, the Cu(II)
      centers are bridged by a phenolate group and an external hydroxide ligand. The
      phenolate group is generated from the evolution of 4c via intramolecular arene
      hydroxylation. (b) For 5e, the two Cu(II) centers are bridged by two hydroxide
      ligands. (c) For the 8e case, the Cu(II) centers are ligated to terminally bound
      hydroxide ligands, rare because of its tendency to bridge. The evolution of
      complexes 1c-8c toward their oxidized species has also been rationalized by DFT
      calculations based mainly on their structure and electrophilicity. The structural
      diversity of the oxidized species is also responsible for a variety of magnetic
      behavior: (a) strong antiferromagnetic (AF) coupling with J = -482.0 cm(-1) (g =
      2.30; rho = 0.032; R = 5.6 x 10(-3)) for 4e; (b) AF coupling with J = -286.3 cm(
      1) (g = 2.07; rho = 0.064; R = 2.6 x 10(-3)) for 5e; (c) an uncoupled Cu(II)2
      complex for 8e.

PMID- 16634588
TI  - Structure, luminescence, and adsorption properties of two chiral microporous
      metal-organic frameworks.
AB  - Two 3D chiral multifunctional microporous MOFs, Zn3(BTC)2(DMF)3(H2O).(DMF)(H2O)
      (1) and Cd(4)(BTC)3(DMF)2(H2O)2.6(H2O) (2) (H(3)BTC = 1,3,5-benzenetricarboxylic
      acid and DMF = N,N'-dimethylformamide), have been synthesized in the presence of
      organic bases tributylamine (TBA) and triethylamine (TEA), respectively. 1
      (C(30)H(38)N(4)O(18)Zn(3)) crystallizes in the tetragonal P4(1)2(1)2 space group
      (a = 13.6929(19) A, c = 50.664(10) A, V = 9499(3) A(3), and Z = 8). 2
      (C33H39N2O28Cd4) crystallizes in the tetragonal P4(3)22 space group (a =
      10.3503(4) A, c = 52.557(3) A, V = 5630.4(4) A(3), and Z = 4). X-ray
      crystallography reveals that 1 consists of a 3D open framework with the
      (6(3))(4)(6(2).8(2).10(2))(6.(4)8(2))(2) topology, but 2 exhibits a 3D open
      network with the (4(2).5)(2)(4.(4)5.(10)6.(8)7.(4)8(2)) topology. The solid-state
      excitation-emission spectra show that the strongest excitation peaks for 1 and 2
      are at 341 and 319 nm, and their emission spectra mainly show strong peaks at 410
      and 405 nm, respectively. The amounts adsorbed of 1 (2) are 169 mg/g (126 mg/g)
      for H2O, 137 mg/g (102 mg/g) for C2H5OH, and 133 mg/g (99 mg/g) for CH3OH, which
      are equivalent to the adsorption of about 62 (34) H2O, 20 (11) C2H5OH, and 28
      (16) CH3OH per unit cell, respectively.

PMID- 16634589
TI  - Syntheses, structures, ionic conductivities, and magnetic properties of three new
      transition-metal borophosphates Na5(H3O){M(II)3[B3O3(OH)]3(PO4)6}.2H2O (M(II) =
      Mn, Co, Ni).
AB  - Three new open-framework transition-metal borophosphates
      Na5(H3O){M(II)3[B3O3(OH)]3(PO4)6}.2H2O (M(II) = Mn, Co, Ni) (denoted as MBPO
      CJ25) have been synthesized under mild hydrothermal conditions. Single-crystal X
      ray diffraction analyses reveal that the three compounds possess isostructural
      three-dimensional (3D) open frameworks with one-dimensional 12-ring channels
      along the [001] direction. Notably, the structure can also be viewed as composed
      of metal phosphate layers [M(II)(PO4)2]4- with Kagome topology, which are further
      connected by [B3O7(OH)] triborates, giving rise to a 3D open framework. The guest
      water molecules locate in the 12-ring channels. Partial Na+ ions reside in the 10
      ring side pockets within the wall of the 12-ring channels, and the other Na+ ions
      and protonated water molecules locate in the 6-ring windows delimited by MO6 and
      PO4 polyhedra to compensate for the negative charges of the anionic framework.
      These compounds show a high thermal stability and are stable upon calcinations at
      ca. 500 degrees C. Ionic conductivities, due to the motion of Na+ ions, are
      measured for these three compounds. They have similar activation energies of 1.13
      1.25 eV and conductivities of 2.7 x 10(-7)-9.9 x 10(-7) S cm(-1) at 300 degrees
      C. Magnetic measurements reveal that there are very weak antiferromagnetic
      interactions among the metal centers of the three compounds. Crystal data: MnBPO
      CJ25, hexagonal, P6(3)/m (No. 176), a = 11.9683(5) A, c = 12.1303(6) A, and Z =
      2; CoBPO-CJ25, hexagonal, P6(3)/m (No. 176), a = 11.7691(15) A, c = 12.112(2) A,
      and Z = 2; NiBPO-CJ25, hexagonal, P6(3)/m (No. 176), a = 11.7171(5) A, c =
      12.0759(7) A, and Z = 2.

PMID- 16634590
TI  - Effects of tris(pyrazolyl)borato ligand substituents on dioxygen activation and
      stabilization by copper compounds.
AB  - Dinuclear [Cu2(mu-O)2(Tp(R,R')2] complexes, analogues of the active site of
      oxyhemocyanin, are theoretically studied, and the effect of the substituents of
      the tris(pyrazolyl)borate ligands, Tp(R,R'), is analyzed. Density functional
      theory calculations reveal that the type of bridging oxygen, peroxo, or bisoxo is
      strongly influenced by the nature and position of the R substituents because of
      variable substituent...bridging oxygen interactions, as well as electronic
      effects. The electronic effects of ligands at the 5 position are not significant,
      but peroxo complexes are favored by electron-withdrawing groups at the 3 position
      while bisoxo ones are strongly sterically disfavored.

PMID- 16634591
TI  - Synthesis, structure, and characterization of novel two- and three-dimensional
      vanadates: Ba2.5(VO2)3(SeO3)4.H2O and La(VO2)3(TeO6).3H2O.
AB  - Two new vanadates, Ba(2.5)(VO2)3(SeO3)4.H2O and La(VO2)3(TeO6).3H2O, have been
      synthesized by hydrothermal methods using BaCO3, Ba(OH)2.H2O, La(NO3)3.6H2O,
      V2O5, TeO2, and H2SeO3 as reagents. The structures were determined by single
      crystal X-ray diffraction. Ba(2.5)(VO2)3(SeO3)4.H2O exhibits a two-dimensional
      layered structure consisting of VO(5) square pyramids and SeO3 polyhedra, whereas
      La(VO2)3(TeO6).3H2O has a three-dimensional framework structure composed of VO(4)
      tetrahedra and TeO6 octahedra. Infrared and Raman spectroscopy, UV-vis diffuse
      reflectance spectroscopy, and thermogravimetric analysis are also presented.
      Crystal data: Ba(2.5)(VO2)3(SeO3)4.H2O, trigonal, space group P (No. 147) with a
      = b = 12.8279(15) A, c = 7.2631(9) A, V = 1035.1(2) A(3), and Z = 2;
      La(VO2)3(TeO6).3H2O, trigonal, space group R3c (No. 161) with a = b = 9.4577(16)
      A, c = 23.455(7) A, V = 1816.9(7) A3, and Z = 6.

PMID- 16634592
TI  - Multiple bicyclic diamide-lutetium complexes in solution: chemometric analysis of
      deep-UV Raman spectroscopic data.
AB  - The investigation of complex formation between a bicyclic diamide, a novel
      chelating agent for lanthanides and actinides, and lutetium in an acetonitrile
      solution is reported. A free ligand and its lutetium complexes showed weak,
      noncharacteristic near-UV absorption and no fluorescence, which limited the
      application of absorption and fluorescence spectroscopies for studying this
      system. Deep-UV Raman spectroscopy combined with chemometric analysis was shown
      to be a powerful tool for quantitative characterization of multiple equilibria
      between lutetium and a bicyclic diamide. Several chemometric methods were
      utilized for a comparative analysis of Raman spectroscopic data. It was found
      that a recently developed stepwise maximum angle calculation algorithm followed
      by alternative least squares (ALS) was more efficient than the commonly used
      combination of evolving factor analysis and ALS methods, especially when little
      or no information about the system composition and the spectra of individual
      components was available. A free ligand and 1:1, 1:2, and 1:3 metal-ligand
      complexes were distinguished in a bicyclic diamide-lutetium solution. The
      composition evolution of the solution during the course of titration with
      lutetium was described, and the stepwise stability constants of complex
      formation, K(1):K(2) = 0.80 +/- 0.15 (K(1,2) > 10(8) M(-1)) and K(3) = (5.5 +/-
      1) x 10(3) M(-1), were estimated.

PMID- 16634593
TI  - Mechanistic information from low-temperature rapid-scan and NMR measurements on
      the protonation and subsequent reductive elimination reaction of a
      (diimine)platinum(II) dimethyl complex.
AB  - A detailed kinetic study of the protonation and subsequent reductive elimination
      reaction of a (diimine)platinum(II) dimethyl complex was undertaken in
      dichloromethane over the temperature range of -90 to +10 degrees C by stopped
      flow techniques. Time-resolved UV-vis monitoring of the reaction allowed the
      assessment of the effects of acid concentration, coordinating solvent (MeCN)
      concentration, temperature, and pressure. The second-order rate constant for the
      protonation step was determined to be 15200 +/- 400 M(-1) s(-1) at -78 degrees C,
      and the corresponding activation parameters are DeltaH = 15.2 +/- 0.6 kJ mol(-1)
      and DeltaS = -85 +/- 3 J mol(-1) K(-1), which are in agreement with the addition
      of a proton that results in the formation of the platinum(IV) hydrido complex.
      The kinetics of the second, methane-releasing reaction step do not show an acid
      dependence, and the MeCN concentration also does not significantly affect the
      reaction rate. The activation parameters for the second reaction step were found
      to be DeltaH = 75 +/- 1 kJ mol(-1), DeltaS = +38 +/- 5 J mol(-1) K(-1), and
      DeltaV = +18 +/- 1 cm(3) mol(-1), strongly suggesting a dissociative character of
      the rate-determining step for the reductive elimination reaction. The
      spectroscopic and kinetic observations were correlated with NMR data and assisted
      the elucidation of the underlying reaction mechanism.

PMID- 16634594
TI  - Synthesis and thermodynamic evaluation of mixed hexadentate linear iron chelators
      containing hydroxypyridinone and terephthalamide units.
AB  - A series of new linear iron chelators containing hydroxypyridinone and
      terephthalamide (TAMmeg) moieties have been prepared. All are hexadentate ligands
      composed of a systematically varied combination of methyl-3,2-hydroxypyridinone
      and 2,3-dihydroxyterephthalamide binding units; most are based on a spermidine
      scaffold, but one incorporates the bifunctional 2,3-dihydroxyterephthalamide unit
      as an integral part of the backbone. Protonation and ferric iron complex
      formation constants have been determined from solution thermodynamic studies,
      giving log beta(110) values of 25.7, 30.7, 36.3, 43.8, and 45.0, respectively.
      The ferric complexes display reversible reduction potentials from -276 to -1032
      mV (measured relative to the normal hydrogen electrode) in alkaline solution. The
      incremental replacement of hydroxypyridinone units by terephthalamide binding
      groups progressively reduces the ligand acidity, markedly increases the iron
      chelate stability, and improves the selectivity for the ferric ion over the
      ferrous ion. While the majority of iron chelators forming very stable ferric
      complexes are based on a tripodal backbone such as TREN, the ferric 5
      LIO(TAMmeg)(2)(TAM) complex, despite its nontripodal scaffold, is one of the most
      stable iron complexes yet reported. Moreover, the high affinity for the ferric
      ion of the discussed linear ligands strongly correlates with their ability to
      remove iron in vivo.

PMID- 16634595
TI  - Determination of the solution structures of melamine-based bis- and tris
      macrocyclic ligand copper(II) complexes.
AB  - A combination of molecular mechanics (MM), electron paramagnetic resonance
      spectroscopy (EPR), and spectra simulation (MM-EPR) has been used to determine
      the solution structures of di- and trinuclear copper(II) complexes of melamine
      based oligomacrocyclic ligands. The spin Hamiltonian parameters of the
      mononuclear, melamine-appended macrocyclic ligand copper(II) complex have been
      determined by EPR spectroscopy and were also studied with DFT methods. These spin
      Hamiltonian parameters, together with the structural parameters obtained from
      models optimized with MM, have been used for the simulation of the EPR spectra of
      the di- and trinuclear complexes. For the dinuclear complex, the syn isomer is
      preferred over the anti, for which an X-ray structure exists; for the trinuclear
      complex, the syn,syn isomer is preferred over the syn,anti form. Additional
      support for these assignments comes from DFT calculations, and this demonstrates
      that the MM-DFT-EPR method is a reliable approach for the determination of
      solution structures and for the analysis of spin Hamiltonian parameters of
      dipolar, coupled transition metal complexes (g and A tensors and J values).

PMID- 16634596
TI  - Equatorially connected diruthenium(II,III) units toward paramagnetic
      supramolecular structures with singular magnetic properties.
AB  - The reaction of Ru2Cl(O2CMe)(DPhF)3 (DPhF = N,N'-diphenylformamidinate) with mono
      and polycarboxylic acids gives a clean substitution of the acetate ligand,
      leading to the formation of complexes Ru2Cl(O2CC6H5)(DPhF)3 (1), Ru2Cl(O2CC6H4-p
      CN)(DPhF)3 (2), [Ru2Cl(DPhF)3(H2O)]2(O2C)2 (3), [Ru2Cl(DPhF)3]2[C6H4-p-(CO2)2]
      (4), and [Ru2Cl(DPhF)3]3[C6H3-1,3,5-(CO2)3] (5). The preparation of
      [Ru2(NCS)(DPhF)3]3[C6H3-1,3,5-(CO2)3] (6) and {[Ru2(DPhF)3(H2O)]3[C6H3-1,3,5
      (CO2)3]}(SO3CF3)3 (7) from 5 is also described. All complexes are characterized
      by elemental analysis, IR and electronic spectroscopy, mass spectrometry, cyclic
      voltammetry, and variable-temperature magnetic measurements. The crystal
      structure determinations of complexes 2.0.5THF and 3.THF.4H2O (THF =
      tetrahydrofuran) are reported. The reactions carried out demonstrate the high
      chemical stability of the fragment [Ru2(DPhF)3]2+, which is preserved in all
      tested experimental conditions. The stability of this fragment is also
      corroborated by the mass spectra. Electrochemical measurements reveal in all
      complexes one redox process due to the equilibrium Ru2(5+) <--> Ru2(6+). In the
      polynuclear complex 7, some additional oxidation processes are also observed that
      have been ascribed to the presence of two types of dimetallic units rather than
      two consecutive reversible oxidations. The magnetic behavior toward temperature
      for complexes 1-7 from 300 to 2 K is analyzed. Complexes 1-7 show low values of
      antiferromagnetic coupling in accordance with the molecular nature in 1 and 2 and
      the absence of important antiferromagnetic interaction through the carboxylate
      bridging ligands in 3-7, respectively. In addition, the magnetic properties of
      complex 7 do not correspond to any magnetic behavior described for
      diruthenium(II,III) complexes. The experimental data of compound 7 are simulated
      considering a physical mixture of S = 1/2 and 3/2 spin states. This magnetic
      study demonstrates the high sensitivity of the electronic configuration of the
      unit [Ru2(DPhF)3]2+ to small changes in the nature of the axial ligands. Finally,
      the energy gap between the pi and delta orbitals in these types of compounds
      allows the tentative assignment of the transition pi --> delta.

PMID- 16634597
TI  - Borohydride, azide, and chloride anions as terminal ligands on Fe/Mo/S clusters.
      Synthesis, structure and characterization of [(Cl4-cat)(PPr3)
      MoFe3S4(X)2]2(Bu4N)4 and [(Cl4-cat)(PPr3)MoFe3S4 (PPr3)(X)]2(Bu4N)2 (X = N3-, BH4
      , Cl-) double-fused cubanes. NMR reactivity studies of [(Cl4-cat)(PPr3)
      MoFe3S4(BH4)2]2(Bu4N)4.
AB  - Our explorations of the reactivity of Fe/Mo/S clusters of some relevance to the
      FeMoco nitrogenase have led to new double-fused cubane clusters with the Mo2Fe6S8
      core as derivatives of the known (Cl4-cat)2Mo2Fe6S8(PPr3)6 (I) fused double
      cubane. The new clusters have been obtained by substitution reactions of the PPr3
      ligands with Cl-, BH4-, and N3-. By careful control of the conditions of these
      reactions, the clusters [(Cl4-cat)(PPr3)MoFe3S4(BH4)2]2(Bu4N)4 (II), [(Cl4
      cat)(PPr3)MoFe3S4(PPr3)(BH4)]2(Bu4N)2 (III), [(Cl4
      cat)(PPr3)MoFe3S4(N3)2]2(Bu4N)4 (IV), [(Cl4-cat)(PPr3)MoFe3S4(PPr3)(N3)]2(Bu4N)2
      (V), and [(Cl4-cat)(PPr3)MoFe3S4Cl2]2(Et4N)4 (VI) have been obtained and
      structurally characterized. A study of their electrochemistry shows that the
      reduction potentials for the derivatives of I are shifted to more positive values
      than those of I, suggesting a stabilization of the reduced clusters by the
      anionic ligands BH4- and N3-. Using 1H NMR spectroscopy, we have explored the
      lability of the BH4- ligand in II in coordinating solvents and its hydridic
      character, which is apparent in its reactivity toward proton sources such as MeOH
      or PhOH.

PMID- 16634598
TI  - Fe(III)-coordination properties of neuromelanin components: 5,6-dihydroxyindole
      and 5,6-dihydroxyindole-2-carboxylic acid.
AB  - The Fe(III)-coordination chemistry of neuromelanin building-block compounds, 5,6
      dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and 5,6
      dihydroxy-N-methyl-indole (Me-DHI), and the neurotransmitter dopamine were
      explored in aqueous solution by anaerobic pH-dependent spectrophotometric
      titrations. The Fe(III)-binding constants and pH-dependent speciation parallel
      those of catechol in that mono, bis, and tris FeLx species are present at
      concentrations dependent on the pH. The bis FeL2 dihydroxyindole species are
      favorable for L = DHI and DHICA under neutral to mildly acidic conditions. DHI
      and DHICA are stronger Fe(III) chelates than catechol, dopamine, and Me-DHI at pH
      values from 3 to 10. Oxidation studies reveal that iron accelerates the air
      oxidation of DHI and DHICA.

PMID- 16634599
TI  - Synthesis, structure, and magnetic properties of Cs(2-x)RbxCu3P4O14 (0.0 </= x
      </= 0.8): a new series of copper(II) phosphates containing periodic arrays of
      staggered square-planar CuO4 trimers.
AB  - In our continued exploratory synthesis of compounds containing transition-metal
      oxide magnetic nanostructures, a new copper(II) phosphate phase, Cs2Cu3P4O14 (1),
      was isolated employing the mixed CsCl/2CsI molten flux. The X-ray single-crystal
      structural analysis shows that the Cs2Cu3P4O(14) phase crystallizes in a
      monoclinic space group with a = 7.920(2) A, b = 10.795(2) A, c = 7.796(2) A, beta
      = 103.90(3) degrees , and V = 646.9(2) A(3); P2(1)/c (No. 14); Z = 2. The
      structure has been refined by the full-matrix least-squares method to a final
      solution with R1 = 0.0248, wR2 = 0.0553, and GOF = 1.02. The three-dimensional Cu
      O-P framework exhibits pseudo-one-dimensional channels where the Cs+ cations
      reside. The framework consists of trimeric CuO4 square-planar units stacked in a
      staggered configuration. These CuO4 trimers are interlinked by the P2O7 units via
      vertex-sharing O atoms. The stacked CuO4 units are slanted with respect to the
      Cu...Cu...Cu vector, resulting in additional Cu-O long bonds, 2.71(1) A, and a
      possibly shortened Cu...Cu distance, 3.38(3) A. 1 shows limited cation
      substitution with smaller alkali-metal cations; in fact, only a relatively small
      concentration of Cs+ can be substituted by Rb+ to form Cs(2-x)RbxCu3P4O14 (0.0
      </= x </= 0.8). The temperature-dependent magnetic susceptibility studies of 1
      and its Rb-substituted analogues (x = 0, 0.33, 0.50, and 0.80) reveal a weak
      ferromagnetic transition at Tc = approximately 14 K, which evidently is
      independent of the variation of x. In this paper, we report the synthesis,
      structure, and properties of the title compounds, as well as its brief comparison
      with the previously discovered Li2Cu3Si4O12 phase, which exhibits fused square
      planar CuO4 trimers.

PMID- 16634600
TI  - 2D and 3D Cu(hfac)2 complexes with nitronyl nitroxide biradicals.
AB  - Reactions between Cu(hfac)2 and nitronyl nitroxide biradicals 1,4-bis[4-(4,4,5,5
      tetramethyl-3-oxide-1-oxyl-4,5-dihydro-1H-imidazol-2-yl)pyrazol-1-yl]butane (L4)
      and 1,8-bis[4-(4,4,5,5-tetramethyl-3-oxide-1-oxyl-4,5-dihydro-1H-imidazol-2
      yl)pyrazol-1-yl]octane (L8) gave respectively a framework compound [Cu(hfac)2]2L4
      and a layered polymer compound [Cu(hfac)2]2L8. The framework of [Cu(hfac)2]2L4
      consists of 66-membered condensed metallocycles. Inside the framework, the
      structure has macrohelixes (pitch approximately 25 A) extending along the [001]
      crystallographic direction. All the helixes have the same direction of winding;
      the crystals, therefore, are optically active, the structure corresponding either
      to P-isomer (P4(1)2(1)2) or to M-isomer (P4(3)2(1)2). The long distances between
      the Cu atoms and the O atoms of the coordinated >N-O groups (Cu-O 2.351-2.467 A)
      are responsible for ferromagnetic exchange interactions in Cu2+-O-N< and >N-O
      Cu2+-O-N< exchange clusters.

PMID- 16634601
TI  - Three novel silver complexes with ligand-unsupported argentophilic interactions
      and their luminescent properties.
AB  - Three novel silver complexes, namely, [Ag5(CN)5(bipy)2]n (1) with a 1-D to 3-D
      architecture constructed through ligand-unsupported argentophilic interactions,
      [Ag5(SCN)4(CN)(bipy)2]n (2) with a 2-D interesting topology formed by cyanide
      groups linking [Ag5(SCN)4(bipy)2]n(n+) cationic columns, and [(Me4N)Ag3(CN)4]n
      (3) with 3-fold-interpenetrated 3-D 3-connected (10, 3)-g nets, have been
      solvothermally synthesized, and all exhibit efficient luminescence.

PMID- 16634602
TI  - Porphyrazines as molecular scaffolds: flexible syntheses of novel multimetallic
      complexes.
AB  - Reductive deselenation of selenodiazole-fused porphyrazines, followed by
      acylation of the resultant labile porphyrazinediamines, was used to prepare
      macrocycles bearing two Collins ligands, two oxamido residues, or two quinoline-2
      carboxamido units. Peripheral coordination of copper(II) to the di-(quinoline-2
      carboxamido)-porphyrazine gave a metal-linked face-to-face porphyrazine dimer
      array. Sequential derivatization of the two amino groups in the
      porphyrazinediamines was used to prepare mixed peripheral ligand systems
      including a dimetallic picolinamido-Schiff base porphyrazine. Such systems
      exhibit strong metal-metal spin coupling and are anticipated to be of value in
      the synthesis of novel electronic and magnetic materials.

PMID- 16634603
TI  - Novel cation [N(SO2NMe3)2]+ and its synthesis and crystal structure. Dichloride
      of imido-bis(sulfuric) acid HN(SO2Cl)2. Part 1. Crystal structures of
      KN(SO2Cl)2.(1/2)CH3CN, KN(SO2Cl)2.(1/6)CH2Cl2, and [PCl4][N(SO2Cl)2].
AB  - Several salts of bis(chlorosulfonyl)imide HN(SO2Cl)2 (1), namely, two solvates of
      its potassium salt, KN(SO2Cl)2.(1/2)CH3CN (1K1), KN(SO2Cl)2.(1/6)CH2Cl2 (1K2),
      and its tetrachlorophosphonium salt, [PCl4][N(SO2Cl)2] (2), were prepared and
      structurally characterized. The reaction of HN(SO2Cl)2 with Me3N gives the
      [N(SO2Cl)2]- salt of a novel cation, [N(SO2NMe3)2]+. This cation is analogous to
      the [HC(SO2NMe3)2]+ cation, but in contrast to the latter, it is fairly stable to
      hydrolysis. The salt [N(SO2NMe3)2]+[N(SO2Cl)2]- (3) can be converted into salts
      of other anions by being treated with diluted aqueous solutions of the respective
      acids, and thus NO3-, Cl-.H2O, SeO3(2-), CH3COO-, HSO4-, (COO)2(2-) salts were
      prepared. Treatment of 3 with concentrated HNO3 gave the [N(SO2NMe3)2]+ [O2NO-H
      ONO2]- salt, and the addition of an HCl-acidified FeCl3 aqueous solution yielded
      the FeCl4- salt. Methanolysis resulted in the formation of MeOSO3- and
      [MeOSO2NSO2OMe]- salts. All salts have been characterized by chemical analysis,
      vibrational spectroscopy, and X-ray structure determinations.

PMID- 16634604
TI  - Memory devices based on lanthanide (Sm3+, Eu3+, Gd3+) complexes.
AB  - Memory effects in single-layer organic light-emitting devices based on Sm3+,
      Gd3+, and Eu3+ rare earth complexes were realized. The device structure was
      indium-tin-oxide (ITO)/3,4-poly(ethylenedioxythiophene)-poly(styrenesulfonate)
      (PEDOT)/Poly(N-vinyl carbazole) (PVK): rare earth complex/LiF/Ca/Ag. It was found
      experimentally that all the devices exhibited two distinctive bistable
      conductivity states in current-voltage characteristics by applying negative
      starting voltage, and more than 10(6) write-read-erase-reread cycles were
      achieved without degradation. Our results indicate that the rare earth organic
      complexes are promising materials for high-density, low-cost memory application
      besides the potential application as organic light-emitting materials in display
      devices.

PMID- 16634605
TI  - Various coordination modes of the bis(di(o-N,N-dimethylanilinyl)phosphino)methane
      ligand in mononuclear and binuclear complexes of group 8 and group 9 metals.
AB  - The synthesis and characterization of a series of compounds involving the
      bis(di(o-N,N-dimethylanilinyl)phosphino)methane (dmapm) ligand are described. The
      mononuclear complexes [MCl(CO)(P,N-dmapm)] (M = Rh, Ir) have a square-planar
      geometry in which the dmapm ligand chelates via a phosphine functionality and an
      adjacent amino group. The carbonyl ligand lies opposite the amine, while the
      chloro ligand is trans to the phosphine. The related complex [RhI(CO)(P,N-dmapm)]
      has also been prepared. All compounds are highly fluxional by at least three
      independent processes, as discussed for the rhodium-chloro species. A diiridium
      complex, [Ir(2)Cl2(CO)2(P,N,P',N'-dmapm)], and the closely related
      rhodium/iridium analogue, [RhIrCl2(CO)2(P,N,P',N'-dmapm)], have been prepared in
      which the metals are bridged by the diphosphine group while an amino group at
      each end of the diphosphine is also coordinating to each metal on opposite faces
      of the MIrP2 plane (M = Ir or Rh). For the Ir2 species, the carbonyl and chloro
      groups are again shown to be opposite the amine and phosphine functionalites,
      respectively. The mononuclear complex [Ru(CO)3(P,P'-dmapm)] has also been
      prepared. In contrast to the mononuclear species of rhodium and iridium, the
      dmapm group chelates the ruthenium center through both phosphorus atoms,
      occupying one axial and one equatorial site of Ru in a distorted trigonal
      bipyramidal geometry. Reaction of this Ru species with 1/2 equiv of the complexes
      [RhClL2]2 (L2 = COD, (C2H4)2, (CO)2) yields the unstable Rh/Ru product
      [RhRuCl(CO)3(P,N,P',N'-dmapm)].

PMID- 16634606
TI  - Pressure effect on bulk weak ferromagnets: (BDH-TTP)[M(isoq)2(NCS)4] (M =
      Cr(III), Fe(III); isoq = Isoquinoline).
AB  - The pressure dependence of the magnetic properties of weak ferromagnets (BDH
      TTP)[M(isoq)2(NCS)4] [BDH-TTP = 2,5-bis(1',3'-dithiolan-2'-ylidene)-1,3,4,6
      tetrathiapentalene; M = Cr, Fe; isoq = isoquinoline] is discussed. These salts
      form two-dimensional magnetic sheets, where ferrimagnetic chains of donor cation
      radical (S = 1/2) and anion [S = 3/2 (Cr), 5/2 (Fe)] are antiferromagnetically
      connected by weak donor-donor and anion-anion interchain S...S contacts. Under
      ambient pressure, both the Cr and Fe salts undergo a weak ferromagnetic
      transition at Tc = 7.6 K, below which a spontaneous magnetization emerges along
      the direction perpendicular to the sheets. The application of the pressure
      elevates the transition temperatures up to 16.6 and 11.6 K at 9 kbar for M = Cr
      and Fe, respectively. As the pressure increases, the remanent magnetization M(r)
      decreases, whose pressure dependence for the Cr salt is larger than that for the
      Fe salt. This difference indicates that the spin-canting angle of the Cr salt is
      reduced because of the increase of antiferromagnetic interaction by applied
      pressure, in contrast to the Fe salt, where single-ion anisotropy contributes
      less. The quantitative analysis of the magnetization curves of the Cr salt using
      the mean-field approximation reveals that the intermolecular exchange interaction
      increases as the pressure increases, among which the interchain anion-anion
      interaction has the highest pressure sensitivity. This result is consistent with
      the temperature dependence of the crystal structure showing that the thermal
      contraction in the distances of interchain anion-anion S...S contacts is the most
      remarkable in intrachain S...S contacts. The large pressure dependence of the
      transition temperature of these salts is therefore explained as a result of the
      fact that the interchain interactions, the anion-anion interaction in particular,
      are strengthened by applied pressure.

PMID- 16634607
TI  - Extending the time: solvothermal syntheses, crystal structures, and properties of
      two non-isostructural thioantimonates with the composition [Mn(tren)]Sb2S4.
AB  - The two novel compounds, [Mn(tren)]Sb2S4 (1 and 2), were obtained by the reaction
      of elemental Mn, Sb, and S in aqueous solutions of tren (tren = tris(2
      aminoethyl)amine, C6H18N4) after different reaction times. Compound 1 is formed
      up to a reaction time of 13 d, and an extension of the reaction time leads to the
      formation of 2. Both compounds crystallize in monoclinic space groups (1,
      P2(1)/c; 2, C2/c). In 1, the two unique SbS3 trigonal pyramids share a common S
      atom to form a Sb2S5 unit. Two S atoms of this group have a bond to Mn2+ yielding
      a MnSb2S3 heteroring in the boat conformation. The Sb2S5 moieties are joined via
      common corners into the final undulated [Sb2S4]2- anion which is directed along
      [001]. The structure of 2 contains the [Mn(tren)]2+ ion, one SbS3 pyramid, and a
      SbS4 unit. Two symmetry-related SbS4 groups share an edge, forming a Sb2S6 group
      containing a Sb2S2 ring. This group is joined via corners to two SbS3 pyramids on
      both sides producing a Sb4S4 ring. The Sb2S2 and Sb4S4 rings are condensed into
      the final [Sb2S4]2- anion which runs along [010]. The [Mn(tren)] groups are bound
      to the thioantimonate(III) backbone on opposite sides of the Sb4S4 ring, and a
      small MnSbS2 ring is formed. In both structures, weak S...H bonds are found which
      may contribute to the stability of the materials. The two compounds decompose in
      one step upon heating, and only MnS and Sb2S3 could be identified as the
      crystalline part of the decomposition products. Both compounds can also be
      prepared under solvothermal conditions using MnSb2S4 as starting material.
      Compounds 1 and 2 are obtained from this ternary material in a high yield.

PMID- 16634608
TI  - Mechanistic analysis of the electrocatalytic properties of dissolved alpha and
      beta isomers of [SiW12O40]4- and solid [Ru(bipy)3]2[alpha-SiW12O40] on the
      reduction of nitrite in acidic aqueous media.
AB  - Voltammetric studies on the reduction of alpha and beta isomers of the Keggin
      polyoxometalate anion [SiW12O40]4- reveal a series of electrochemically
      reversible processes in acidic aqueous media. In the presence of NO2-, catalytic
      current is detected in the potential region of the [SiW12O40]4-/5- process.
      Electronic spectroscopy and simulation of voltammetric data undertaken at
      variable [NO2-] and [H+] allow the following mechanism to be postulated,
      [SiW12O40]4- + e- <-->[SiW12O40]5-, H+ + HNO2 <--> NO+ + H2O, NO+ + [SiW12O40]5- 
      -> NO + [SiW12O40]4-. The second-order rate constant for the rate-determining
      step is faster for the alpha isomer than for the beta one. This may be attributed
      to the different reversible potentials of -0.144 V (alpha isomer) and -0.036 V vs
      Ag/AgCl (beta isomer) and, hence, smaller driving force for an assumed outer
      sphere electron-transfer reaction in the case of beta isomer. A stable, water
      insoluble, thin-film [Ru(bipy)3]2[alpha-SiW12O40] chemically modified electrode
      was generated electrochemically via ion-exchange of [Ru(bipy)3]2+ with Bu4N+ in
      the [Bu4N]4[alpha-SiW12O40] solid. The first reduction process with this modified
      electrode gives rise to the reaction [Ru(bipy)3]2[alpha-SiW12O40](solid) +
      H+(soln) + e- <--> H[Ru(bipy)3]2[alpha-SiW12O40](solid). The need to transfer a
      proton from the solution to the solid phase for charge neutralization purposes
      introduces a hydrogen-ion concentration dependence into this reaction, which is
      not found in the solution-phase study. Nevertheless, the voltammetric catalytic
      activity with respect to nitrite reduction is retained with the chemically
      modified electrode. However, nitrite catalysis with the [Ru(bipy)3]2[alpha
      SiW12O40]-modified electrode is now independent of concentration of H+, rather
      than exhibiting a first-order dependence, and full mechanistic details for this
      process are unknown.

PMID- 16634609
TI  - A three-dimensional framework structure constructed from 2-(2-pyridyl-N-oxide)
      ethylphosphonic acid and Nd(III).
AB  - A multistep synthesis for 2-(2-pyridyl-N-oxide) ethylphosphonic acid 6-H2 is
      described along with its spectroscopic (IR, NMR) data and a single-crystal X-ray
      diffraction structure analysis. Combination of the ligand with Nd(OH)3 results in
      the formation of a complex Nd(6-H)3. Single-crystal X-ray diffraction analysis
      reveals a three-dimensional crystal network generated by hydrogen-bonded chains
      along the crystallographic c axis. The hydrogen bonds are formed between
      phosphonic acid anion (6-H)(-1) protons on one chain and pyridyl N-oxide oxygen
      atoms in neighboring chains. The asymmetric unit contains 1/3[Nd(6-H)3] and there
      are two unique Nd(III) atoms, each with point symmetry. As a result, each Nd(III)
      ion is bound to six (6-H)(-1) ligands and the symmetry about the Nd(III) ion is
      octahedral with each vertex occupied by a phosphonate oxygen atom. The Nd-O bond
      lengths are essentially identical: Nd(1)-O(3), 2.336 (1) A; Nd(2)-O(4), 2.340 (1)
      A. The monoanionic ligand (6-H)(-1), therefore, serves to bridge the unique
      Nd(III) centers.

PMID- 16634610
TI  - Synthesis, X-ray crystal structures, magnetism, and phosphate ester cleavage
      properties of copper(II) complexes of N-substituted derivatives of 1,4,7
      triazacyclononane.
AB  - Two new N-substituted derivatives of the 1,4,7-triazacyclononane (tacn)
      macrocycle, 1-benzyl-4,7-dimethyl-1,4,7-triazacyclononane (L2) and 1,4,7-tris(3
      cyanobenzyl)-1,4,7-triazacyclononane (L3), have been prepared and, together with
      1,4-dimethyl-1,4,7-triazacyclononane (L1), have been used to synthesize the
      corresponding hydroxo-bridged binuclear copper (II) complexes, [Cu2(mu
      OH)2L2](ClO4)2.xH2O (1 L = L1, x = 0; 2 L = L2, x = 1; 3 L = L3, x = 2). The X
      ray crystal structures of all three complexes reveal the presence of [Cu2(mu
      OH)2]2+ cores capped by pairs of facially coordinating tacn ligands so that the
      Cu(II) centers reside in distorted square pyramidal coordination environments.
      Variable-temperature magnetic susceptibility measurements indicate weak
      antiferromagnetic coupling (J = -36.4 cm(-1)) between the Cu(II) centers in 1,
      while the centers in 2 and 3 have been shown to interact ferromagnetically (J =
      11.2 and 49.3 cm(-1), respectively). The variation in the strength and sign of
      these interactions has been rationalized in terms of the differing geometries of
      the [Cu2(mu-OH)2]2+ cores. The ability of the Cu(II) complexes to cleave
      phosphate ester bonds has been probed using the model phosphate ester bis(4
      nitrophenyl)phosphate (BNPP) at pH 7.4 and a temperature of 50 degrees C. The
      measured rate constant for 3 (3 x 10(-4) s(-1)) is significantly greater than
      those previously reported for the Cu(II) complexes of the fully alkylated tacn
      ligands, Me3tacn and iPr3tacn, which until now have been rated as the most
      effective tacn-based phosphate ester cleavage agents.

PMID- 16634611
TI  - Photophysical properties and excitation polarization of fac/mer-ruthenium
      complexes with 5'-amino-2,2'-bipyridine-5-carboxylic acid derivatives.
AB  - Novel ruthenium(II) complexes, fac/mer-[Ru(MeCO-5Bpy-R)3]2+ (H-5Bpy-OH = 5'-amino
      2,2'-bipyridine-5-carboxylic acid; R = -NHtBu, -NH(cHex), -N(cHex)2), have been
      synthesized. The fac and mer isomers have been successfully separated using HPLC
      techniques, and their photophysical/electrochemical properties have been
      investigated. In the absorption and emission spectra of fac/mer-[Ru(MeCO-5Bpy
      R)3]2+ with secondary amines (R = -N(cHex)2) in acetonitrile at room temperature,
      the maximum wavelengths based on the MLCT are longer than those for the amide
      derivatives with primary amines (R = -NHtBu, -NH(cHex)). A small solvent effect
      on the photophysical properties between fac- and mer-[Ru(MeCO-5Bpy-NHtBu)3]2+ has
      been observed. The excitation polarization spectra, giving P values reflecting
      the relation between the absorption and the emission oscillators, for the fac-
      and mer-ruthenium(II) complexes (C3 and C1 symmetry, respectively) have been
      measured for the first time. Almost no difference in the excitation polarization
      spectra between the fac and mer complexes is found, and these spectra are similar
      to that for [Ru(bpy)3]2+ with D3 symmetry. This finding suggests that the
      orientations of the absorption and emission oscillators, in the case of the
      ruthenium(II) tris(2,2'-bipyridine) derivatives, would not be affected by the
      symmetries of the complexes and that the P values for any derivatives would be
      similar to that for [Ru(bpy)3]2+.

PMID- 16634612
TI  - Thermal degradation of acetate-intercalated hydroxy double and layered hydroxy
      salts.
AB  - Two hydroxy double salts (HDSs), zinc copper hydroxy acetate (ZCA) and zinc
      nickel hydroxy acetate (ZNA), and an analogous layered compound, zinc hydroxy
      acetate (ZHA), have been prepared by a coprecipitation method. The thermal
      degradation of these materials was characterized via thermogravimetric analysis
      (TGA), differential thermal analysis (DTA), and TGA coupled with Fourier
      transform infrared spectroscopy of gas-phase products, TGA-FTIR. Loss of
      physisorbed and interlayer H2O was observed between 50 and 150 degrees C for all
      compounds. Acetic acid, acetone, water, and CO2 were released at high
      temperatures with relative acetone yields found to be dependent on precursor
      identity, with very little formed from ZCA compared with ZHA and ZNA. Combined
      FTIR and XRD analysis of solid residues extracted at different points in the
      heating profile suggests that ketonization occurs via dissociative adsorption of
      acetic acid on ZnO surfaces. Nanometer-sized ZnO particles were formed from ZHA,
      showing slight preferential growth in the ZnO (002) lattice direction, while the
      presence of a second metal, Ni or Cu, served to retard ZnO crystallite growth at
      temperatures below 600 degrees C and eliminate preferential growth. ZCA leads to
      the formation of reduced copper species (metallic copper and Cu2O) when heated to
      250 degrees C.

PMID- 16634613
TI  - Synthesis, structure, and properties of an Fe(II) carbonyl [(PaPy3)Fe(CO)](ClO4):
      insight into the reactivity of Fe(II)-CO and Fe(II)-NO moieties in non-heme iron
      chelates of N-donor ligands.
AB  - An Fe(II) carbonyl complex [(PaPy3)Fe(CO)](ClO4) (1) of the pentadentate ligand
      N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy3H, H is the
      dissociable amide proton) has been synthesized and structurally characterized.
      This Fe(II) carbonyl exhibits its nu(CO) at 1972 cm(-1), and its 1H NMR spectrum
      in degassed CD3CN confirms its S = 0 ground state. The bound CO in 1 is not
      photolabile. Reaction of 1 with an equimolar amount of NO results in the
      formation of the {Fe-NO}7 nitrosyl [(PaPy3)Fe(NO)](ClO4) (2), while excess NO
      affords the iron(III) nitro complex [(PaPy3)Fe(NO2)](ClO4) (5). In the presence
      of [Fe(Cp)2]+ and excess NO, 1 forms the {Fe-NO}6 nitrosyl [(PaPy3)Fe(NO)](ClO4)2
      (3). Complex 1 also reacts with dioxygen to afford the iron(III) mu-oxo species
      [{(PaPy3)Fe}2O](ClO4)2 (4). Comparison of the metric and spectral parameters of 1
      with those of the previously reported {Fe-NO}6,7 nitrosyls 3 and 2 provides
      insight into the electronic distributions in the Fe(II)-CO, Fe(II)-NO, and Fe(II)
      NO+ bonds in the isostructural series of complexes 1-3 derived from a non-heme
      polypyridine ligand with one carboxamide group.

PMID- 16634614
TI  - Solid state molecular structures of transition metal hexafluorides.
AB  - Single-crystal structure determinations of all nine transition metal
      hexafluorides (Mo, Tc, Ru, Rh, W, Re, Os, Ir, and Pt) at -140 degrees C are
      presented. All compounds crystallize alike and have the same molecular structure.
      The bond length sequence r(w-F) congruent with r(Re-F) congruent with r(Os-F) <
      r(Ir-F) < r(Pt-F) is confirmed and paralleled by the sequence r(Mo-F) congruent
      with r(Tc-F) congruent with r(Ru-F) < r(Rh-F). Within the limits of precision, no
      systematic deviation from octahedral symmetry can be established. DFT and ab
      initio calculations predict octahedral structures for MoF6 and RhF6 and
      tetragonally distorted structures for ReF6 and RuF6. The energy barrier toward
      octahedral structures is only 2.5 kJ mol(-1) in the two latter cases. Calculated
      electron affinities are in the sequence MoF6 < TcF6 < RhF6 < RuF6 with a value of
      6.98 eV for the latter. O2+RhF6- crystallized in an undisordered manner in P,
      isostructural to the low-temperature form of O2+AuF6-. RhF6- has a D4h compressed
      octahedral structure, while AuF6- is essentially octahedral. The absorption
      spectrum of TcF6 and the 19F and 195NMR spectra of PtF6 are presented.

PMID- 16634615
TI  - Effects of steric constraint on Chromium(III) complexes of tetraazamacrocycles.
      3. Insights into the temperature-dependent radiationless deactivation of the 2Eg
      (Oh) excited state of trans-[Cr(N4)(CN)2]+ complexes.
AB  - Macrocyclic complexes of the type trans-[Cr(N4)(CN)2]+, where N4 = cyclam, 1,11
      C3-cyclam, and 1,4-C2-cyclam demonstrate significant variation in their room
      temperature excited-state behavior; namely, the lifetimes of the 2Eg (Oh) excited
      states are 335, 23, and 0.24 micros, respectively. The lifetimes of these
      complexes have been measured in acidified H2O/dimethyl sulfoxide over the
      temperature range between -30 and +95 degrees C. Arrhenius activation parameters
      were calculated from these data. There was very little variation in the values of
      the Arrhenius preexponential factor between these three complexes, whereas the
      value of Ea is 40.6 kJ/mol for the cyclam complex, 35.5 kJ/mol for the 1,11-C3
      cyclam complex, and 22.3 kJ/mol for the 1,4-C2-cyclam complex. Thus, differences
      in the room-temperature excited-state lifetimes can be rationalized based on the
      competition between thermally independent nonradiative relaxation and a thermally
      activated channel. To test whether a photodissociation mechanism involving Cr
      macrocyclic N bond cleavage is a plausible explanation for the thermally
      activated relaxation pathway, samples of the cyclam complex were photolyzed in
      acidified D(2)O. A marked increase in the lifetime after photolysis demonstrated
      the occurrence of photodeuteration and thus a likely photodissociation of a
      macrocyclic N.

PMID- 16634616
TI  - Heteroleptic bis(phthalocyaninato) europium(III) complexes fused with different
      numbers of 15-crown-5 moieties. Synthesis, spectroscopy, electrochemistry, and
      supramolecular structure.
AB  - A series of heteroleptic bis(phthalocyaninato) europium(III) complexes, namely,
      Eu(Pc)[Pc(15C5)] (2), Eu(Pc)[Pc(opp-15C5)2] (3), Eu(Pc)[Pc(adj-15C5)2] (4),
      Eu(Pc)[Pc(15C5)3] (5), and Eu(Pc)[Pc(15C5)4] (6) [Pc = unsubstituted
      phthalocyaninate; Pc(15C5) = 2,3-(15-crown-5)phthalocyaninate; Pc(opp-15C5)2 =
      2,3,16,17-bis(15-crown-5)phthalocyaninate; Pc(adj-15C5)2 = 2,3,9,10-bis(15-crown
      5)phthalocyaninate; Pc(15C5)3 = 2,3,9,10,16,17-tris(15-crown-5)phthalocyaninate,
      Pc(15C5)4 = 2,3,9,10,16,17,24,25-tetrakis(15-crown-5)phthalocyaninate], with one,
      two, three, and four 15-crown-5 voids attached at different positions of one of
      the two phthalocyaninato ligands in the double-decker molecules, have been
      devised and prepared by Eu(Pc)(acac)-induced (Hacac = acetylacetone) mixed
      cyclization of the two corresponding phthalonitriles in the presence of organic
      base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in n-pentanol. For the purpose of
      comparative studies, homoleptic counterparts Eu(Pc)2 (1) and Eu[Pc(15C5)4]2 (7)
      have also been prepared. These sandwich double-decker complexes have been
      characterized by a wide range of spectroscopic methods in addition to elemental
      analysis. Their electrochemistry has also been studied by cyclic voltammetry (CV)
      and differential pulse voltammetry (DPV). The molecular structure of
      Eu(Pc)[Pc(15C5)4] (6) has been determined by X-ray diffraction analysis. Their
      supramolecular structure-formation properties, in particular for compounds 5 and
      6 in the presence of potassium ions, have also been comparatively studied for the
      purpose of future functional investigation.

PMID- 16634617
TI  - CO2 Fixation by Cu2+ and Zn2+ complexes of a terpyridinophane aza receptor.
      Crystal structures of Cu2+ complexes, pH-metric, spectroscopic, and
      electrochemical studies.
AB  - The synthesis of the terpyridinophane-type polyamine 2,6,9,12,16-pentaaza[17]
      (5,5' ')-cyclo-(2,2':6',2' ')-terpyridinophane heptahydrobromide tetrahydrate
      (L.7HBr.4H2O) is described. L presents six protonation constants with values in
      the range 9.21-3.27 logarithmic units. L interacts with Cu2+ and Zn2+ forming in
      both cases, neutral, protonated, and hydroxylated mono- and binuclear complexes
      whose constants have been calculated by potentiometry in 0.15 M NaClO4 at 298.1
      K. The crystal structures of the compounds [Cu(HL-carb)(H2O)](ClO4)3.2H2O (1) and
      [Cu2(H2L)(CO3)]2(ClO4)8.9H2O (2) have been solved by X-ray diffraction. In 1, the
      metal center presents square pyramidal geometry. The base of the pyramid is
      formed by the three nitrogen atoms of pyridine and one oxygen atom of a CO2 group
      which is forming a carbamate bond with the central nitrogen atom of the polyamine
      chain. The axial position is occupied by a water molecule. In 2, one Cu2+ is
      bound by the three pyridine nitrogens and the other one by the three central
      nitrogen atoms of the polyamine chain. The square planar coordination geometry is
      completed by a carbonate group taken up from the atmosphere that behaves as a
      bridging mu,mu'-ligand between the two centers. The pH-metric titrations on the
      ternary Cu2+-L-carbonate and Zn2+-L-carbonate systems show the extensive
      formation of adduct species which above pH 6 are formed quantitatively in
      solution. The stoichiometries of the main species formed in solution at pH = 6.8
      agree with those found in the crystalline compounds. CO2 uptake by the Zn2+ and
      Cu2+ 1:1 complexes in aqueous solution has also been followed by recording the
      variations in the band at ca. 300 nm. The formation of the Zn2+ carbamate moiety
      has been evidenced by 13C NMR and ESI spectroscopy.

PMID- 16634618
TI  - Synthesis and characterization of triazenide and triazene complexes of ruthenium
      and osmium.
AB  - Triazenide [M(eta2-1,3-ArNNNAr)P4]BPh4 [M = Ru, Os; Ar = Ph, p-tolyl; P =
      P(OMe)3, P(OEt)3, PPh(OEt)2] complexes were prepared by allowing triflate
      [M(kappa2-OTf)P4]OTf species to react first with 1,3-ArN=NN(H)Ar triazene and
      then with an excess of triethylamine. Alternatively, ruthenium triazenide
      [Ru(eta2-1,3-ArNNNAr)P4]BPh4 derivatives were obtained by reacting hydride
      [RuH(eta2-H2)P4]+ and RuH(kappa1-OTf)P4 compounds with 1,3-diaryltriazene. The
      complexes were characterized by spectroscopy and X-ray crystallography of the
      [Ru(eta2-1,3-PhNNNPh){P(OEt)3}4]BPh4 derivative. Hydride triazene [OsH(eta1-1,3
      ArN=NN(H)Ar)P4]BPh4 [P = P(OEt)3, PPh(OEt)2; Ar = Ph, p-tolyl] and [RuH{eta1-1,3
      p-tolyl-N=NN(H)-p-tolyl}{PPh(OEt)2}4]BPh4 derivatives were prepared by allowing
      kappa1-triflate MH(kappa1-OTf)P4 to react with 1,3-diaryltriazene. The [Os(kappa1
      OTf){eta1-1,3-PhN=NN(H)Ph}{P(OEt)3}4]BPh4 intermediate was also obtained.
      Variable-temperature NMR studies were carried out using 15N-labeled triazene
      complexes prepared from the 1,3-Ph15N=N15N(H)Ph ligand. Osmium dihydrogen
      [OsH(eta2-H2)P4]BPh4 complexes [P = P(OEt)3, PPh(OEt)2] react with 1,3
      ArN=NN(H)Ar triazene to give the hydride-diazene [OsH(ArN=NH)P4]BPh4 derivatives.
      The X-ray crystal structure determination of the [OsH(PhN=NH){PPh(OEt)2}4]BPh4
      complex is reported. A reaction path to explain the formation of the diazene
      complexes is also reported.

PMID- 16634620
TI  - A coupled dinuclear iron cluster that is perturbed by substrate binding in myo
      inositol oxygenase.
AB  - myo-Inositol oxygenase (MIOX) uses iron as its cofactor and dioxygen as its
      cosubstrate to effect the unique, ring-cleaving, four-electron oxidation of its
      cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate to d-glucuronate. The nature of the
      iron cofactor and its interaction with the substrate, myo-inositol (MI), have
      been probed by electron paramagnetic resonance (EPR) and Mossbauer
      spectroscopies. The data demonstrate the formation of an antiferromagnetically
      coupled, high-spin diiron(III/III) cluster upon treatment of solutions of Fe(II)
      and MIOX with excess O(2) or H(2)O(2) and the formation of an
      antiferromagnetically coupled, valence-localized, high-spin diiron(II/III)
      cluster upon treatment with either limiting O(2) or excess O(2) in the presence
      of a mild reductant (e.g., ascorbate). Marked changes to the spectra of both
      redox forms upon addition of MI and analogy to changes induced by binding of
      phosphate to the diiron(II/III) cluster of the protein phosphatase, uteroferrin,
      suggest that MI coordinates directly to the diiron cluster, most likely in a
      bridging mode. The addition of MIOX to the growing family of non-heme diiron
      oxygenases expands the catalytic range of the family beyond the two-electron
      oxidation (hydroxylation and dehydrogenation) reactions catalyzed by its more
      extensively studied members such as methane monooxygenase and stearoyl acyl
      carrier protein Delta(9)-desaturase.

PMID- 16634621
TI  - Oxygen activation by a mixed-valent, diiron(II/III) cluster in the glycol
      cleavage reaction catalyzed by myo-inositol oxygenase.
AB  - myo-Inositol oxygenase (MIOX) catalyzes the ring-cleaving, four-electron
      oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate (myo-inositol, MI) to
      d-glucuronate (DG). The preceding paper [Xing, G., Hoffart, L. M., Diao, Y.,
      Prabhu, K. S., Arner, R. J., Reddy, C. C., Krebs, C., and Bollinger, J. M., Jr.
      (2006) Biochemistry 45, 5393-5401] demonstrates by Mossbauer and electron
      paramagnetic resonance (EPR) spectroscopies that MIOX can contain a non-heme
      dinuclear iron cluster, which, in its mixed-valent (II/III) and fully oxidized
      (III/III) states, is perturbed by binding of MI in a manner consistent with
      direct coordination. In the study presented here, the redox form of the enzyme
      that activates O(2) has been identified. l-Cysteine, which was previously
      reported to accelerate turnover, reduces the fully oxidized enzyme to the mixed
      valent form, and O(2), the cosubstrate, oxidizes the fully reduced form to the
      mixed-valent form with a stoichiometry of one per O(2). Both observations
      implicate the mixed-valent, diiron(II/III) form of the enzyme as the active
      state. Stopped-flow absorption and freeze-quench EPR data from the reaction of
      the substrate complex of mixed-valent MIOX [MIOX(II/III).MI] with limiting O(2)
      in the presence of excess, saturating MI reveal the following cycle: (1)
      MIOX(II/III).MI reacts rapidly with O(2) to generate an intermediate (H) with a
      rhombic, g < 2 EPR spectrum; (2) a form of the enzyme with the same absorption
      features as MIOX(II/III) develops as H decays, suggesting that turnover has
      occurred; and (3) the starting MIOX(II/III).MI complex is then quantitatively
      regenerated. This cycle is fast enough to account for the catalytic rate. The
      DG/O(2) stoichiometry in the reaction, 0.8 +/- 0.1, is similar to the theoretical
      value of 1, whereas significantly less product is formed in the corresponding
      reaction of the fully reduced enzyme with limiting O(2). The DG/O(2) yield in the
      latter reaction decreases as the enzyme concentration is increased, consistent
      with the hypothesis that initial conversion of the reduced enzyme to the
      MIOX(II/III).MI complex and subsequent turnover by the mixed-valent form is
      responsible for the product in this case. The use of the mixed-valent,
      diiron(II/III) cluster by MIOX represents a significant departure from the
      mechanisms of other known diiron oxygenases, which all involve activation of O(2)
      from the II/II manifold.

PMID- 16634622
TI  - Low-barrier hydrogen bond hypothesis in the catalytic triad residue of serine
      proteases: correlation between structural rearrangement and chemical shifts in
      the acylation process.
AB  - To elucidate the catalytic advantage of the low-barrier hydrogen bond (LBHB), we
      analyze the hydrogen bonding network of the catalytic triad (His57-Asp102-Ser195)
      of serine protease trypsin, one of the best examples of the LBHB reaction
      mechanism. Especially, we focus on the correlation between the change of the
      chemical shifts and the structural rearrangement of the active site in the
      acylation process. To clarify LBHB, we evaluate the two complementary properties.
      First, we calculate the NMR chemical shifts of the imidazole ring of His57 by the
      gauge-including atomic orbital (GIAO) approach within the ab initio QM/MM
      framework. Second, the free energy profile of the proton transfer from His57 to
      Asp102 in the tetrahedral intermediate is obtained by ab initio QM/MM
      calculations combined with molecular dynamics free energy perturbation (MD-FEP)
      simulations. The present analyses reveal that the calculated shifts reasonably
      reproduce the observed values for (1)H chemical shift of H(epsilon)(1) and
      H(delta)(1) in His57. The (15)N and (13)C chemical shifts are also consistent
      with the experiments. It is also shown that the proton between His57 and Asp102
      is localized at the His57 side. This largely downfield chemical shift is
      originated from the strong electrostatic interaction, not a covalent-like bonding
      character between His57 and Asp102. Also, it is proved that a slight downfield
      character of H(epsilon)(1) is originated from a electrostatic interaction between
      His57 and the backbone carbonyl group of Val213 and Ser214. These downfield
      chemical shifts are observed only when the tetrahedral intermediate is formed in
      the acylation process.

PMID- 16634623
TI  - Differentiating a ligand's chemical requirements for allosteric interactions from
      those for protein binding. Phenylalanine inhibition of pyruvate kinase.
AB  - The isoform of pyruvate kinase from brain and muscle of mammals (M(1)-PYK) is
      allosterically inhibited by phenylalanine. Initial observations in this model
      allosteric system indicate that Ala binds competitively with Phe, but elicits a
      minimal allosteric response. Thus, the allosteric ligand of this system must have
      requirements for eliciting an allosteric response in addition to the requirements
      for binding. Phe analogues have been used to dissect what chemical properties of
      Phe are responsible for eliciting the allosteric response. We first demonstrate
      that the l-2-aminopropanaldehyde substructure of the amino acid ligand is
      primarily responsible for binding to M(1)-PYK. Since the allosteric response to
      Ala is minimal and linear addition of methyl groups beyond the beta-carbon
      increase the magnitude of the allosteric response, we conclude that moieties
      beyond the beta-carbon are primarily responsible for allostery. Instead of an all
      or-none mechanism of allostery, these findings support the idea that the bulk of
      the hydrophobic side chain, but not the aromatic nature, is the primary
      determinant of the magnitude of the observed allosteric inhibition. The use of
      these results to direct structural studies has resulted in a 1.65 A structure of
      M(1)-PYK with Ala bound. The coordination of Ala in the allosteric amino acid
      binding site confirms the binding role of the l-2-aminopropanaldehyde
      substructure of the ligand. Collectively, this study confirms that a ligand can
      have chemical regions specific for eliciting the allosteric signal in addition to
      the chemical regions necessary for binding.

PMID- 16634624
TI  - Proton movement and photointermediate kinetics in rhodopsin mutants.
AB  - The role of ionizable amino acid side chains in the bovine rhodopsin activation
      mechanism was studied in mutants E134Q, E134R/R135E, H211F, and E122Q. All
      mutants exhibited bathorhodopsin stability on the 30 ns to 1 micros time scale
      similar to that of the wild type. Lumirhodopsin decay was also similar to that of
      the wild type except for the H211F mutant where early decay (20 micros) to a
      second form of lumirhodopsin was seen, followed by formation of an extremely long
      lived Meta I(480) product (34 ms), an intermediate which forms to a much reduced
      extent, if at all, in dodecyl maltoside suspensions of wild-type rhodopsin. A
      smaller amount of a similar long-lived Meta I(480) product was seen after
      photolysis of E122Q, but E134Q and E134R/R135Q displayed kinetics much more
      similar to those of the wild type under these conditions (i.e., no Meta I(480)
      product). These results support the idea that specific interaction of His211 and
      Glu122 plays a significant role in deprotonation of the retinylidene Schiff base
      and receptor activation. Proton uptake measurements using bromcresol purple
      showed that E122Q was qualitatively similar to wild-type rhodopsin, with at least
      one proton being released during lumirhodopsin decay per Meta I(380) intermediate
      formed, followed by uptake of at least two protons per rhodopsin bleached on a
      time scale of tens of milliseconds. Different results were obtained for H211F,
      E134Q, and E134R/R135E, which all released approximately two protons per
      rhodopsin bleached. These results show that several ionizable groups besides the
      Schiff base imine are affected by the structural changes involved in rhodopsin
      activation. At least two proton uptake groups and probably at least one proton
      release group in addition to the Schiff base are present in rhodopsin.

PMID- 16634625
TI  - Antimitotic sulfonamides inhibit microtubule assembly dynamics and cancer cell
      proliferation.
AB  - Several sulfonamides have antitumor activities and are currently undergoing
      clinical evaluation for the treatment of cancer. In this study, we have
      elucidated the antiproliferative mechanism of action of five indole sulfonamides.
      The indole sulfonamides inhibited the polymerization of microtubule protein into
      microtubules in vitro. In addition, three representative derivatives, ER-68378
      (2), ER-68384 (4) and ER-68394 (5), suppressed the dynamic instability behavior
      at the plus ends of individual steady-state microtubules in vitro. The analogues
      inhibited HeLa cell proliferation with half-maximal inhibitory concentrations in
      the range of 6-17 microM. The compounds blocked cell cycle progression at
      mitosis. At their lowest effective antimitotic concentrations, they depolymerized
      the spindle microtubules and disorganized the chromosomes but did not affect the
      microtubules in interphase cells. However, at relatively high concentrations,
      interphase microtubules were also depolymerized by these sulfonamides.
      Furthermore, all five compounds were found to induce apoptosis in the cells in
      association with the phosphorylation of bcl-2. The results suggest that the
      indole sulfonamides inhibit cell proliferation at mitosis by perturbing the
      assembly dynamics of spindle microtubules and that they can kill cancer cells by
      inducing apoptosis through the bcl-2-dependent pathway.

PMID- 16634626
TI  - A secreted salivary inositol polyphosphate 5-phosphatase from a blood-feeding
      insect: allosteric activation by soluble phosphoinositides and
      phosphatidylserine.
AB  - Type II inositol polyphosphate 5-phosphatases (IPPs) act on both soluble inositol
      phosphate and phosphoinositide substrates. In many cases, these enzymes occur as
      multidomain proteins in which the IPP domain is linked to lipid-binding or
      additional catalytic domains. Rhodnius prolixus IPPRp exists as an isolated IPP
      domain which is secreted into the saliva of this blood-feeding insect. It shows
      selectivity for soluble and lipid substrates having a 1,4,5-trisphosphate
      substitution pattern while only poorly hydrolyzing substrates containing a D3
      phosphate. With soluble diC8 PI(4,5)P(2) as a substrate, sigmoidal kinetics were
      observed, suggesting the presence of allosteric activation sites. Surprisingly,
      IPPRp-mediated hydrolysis of PI(4,5)P(2) and PI(3,4,5)P(3) was also stimulated up
      to 100-fold by diC8 PI(4)P and diC8 phosphatidylserine (PS). The activation
      kinetics were again sigmoidal, demonstrating that the allosteric sites recognize
      nonsubstrate phospholipids. Activation was positively cooperative, and analysis
      by the Hill equation suggests that at least three to four allosteric sites are
      present. In a vesicular system, hydrolysis of PI(4,5)P(2) followed a surface
      dilution kinetic model, and as expected, PS was found to be strongly stimulatory.
      If allosteric activation of type II IPPs by PI(4)P and PS is a widespread feature
      of the group, it may represent a novel regulatory mechanism for these important
      enzymes.

PMID- 16634627
TI  - ATR-FTIR redox difference spectroscopy of Yarrowia lipolytica and bovine complex
      I.
AB  - ATR-FTIR spectroscopy in combination with electrochemistry has been applied to
      the redox centers of Yarrowia lipolytica complex I. The redox spectra show broad
      similarities with previously published data on Escherichia coli complex I and
      with new data here on bovine complex I. The spectra are dominated by amide I/II
      protein backbone changes. Comparisons with redox IR spectra of small model
      ferredoxins demonstrate that these amide I/II changes arise primarily from
      characteristic structural changes local to the iron-sulfur centers, rather than
      from global structural alterations as has been suggested previously. Bands
      arising from the substrate ubiquinone were evident, as was a characteristic 1405
      cm(-)(1) band of the reduced form of the FMN cofactor. Other signals are likely
      to arise from perturbations or protonation changes of a carboxylic amino acid,
      histidine, and possibly several other specific amino acids. Redox difference
      spectra of center N2, together with substrate ubiquinone, were isolated from
      those of the other iron-sulfur centers by selective redox potentiometry. Its
      redox-linked amide I/II changes were typical of those in other 4Fe-4S iron sulfur
      proteins. Contrary to published data on bacterial complex I, no center N2 redox
      linked protonation changes of carboxylic amino acids or tyrosine were evident,
      and other residues that could provide its redox-linked protonation site are
      discussed. Features of the substrate ubiquinone associated with the center N2
      spectrum were particularly clear, with firm assignments possible for bands from
      both oxidized and reduced forms. This is the first report of IR properties of
      ubiquinone in complex I, and the data could be used to estimate a stoichiometry
      of 0.2-0.4 per complex I.

PMID- 16634628
TI  - Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural
      determinants for maintaining sensitivity and developing resistance to atazanavir.
AB  - A series of HIV-1 protease mutants has been designed in an effort to analyze the
      contribution to drug resistance provided by natural polymorphisms as well as
      therapy-selective (active and non-active site) mutations in the HIV-1 CRF_01 A/E
      (AE) protease when compared to that of the subtype B (B) protease. Kinetic
      analysis of these variants using chromogenic substrates showed differences in
      substrate specificity between pretherapy B and AE proteases. Inhibition analysis
      with ritonavir, indinavir, nelfinavir, amprenavir, saquinavir, lopinavir, and
      atazanavir revealed that the natural polymorphisms found in A/E can influence
      inhibitor resistance. It was also apparent that a high level of resistance in the
      A/E protease, as with B protease, is due to it aquiring a combination of active
      site and non-active site mutations. Structural analysis of atazanavir bound to a
      pretherapy B protease showed that the ability of atazanavir to maintain its
      binding affinity for variants containing some resistance mutations is due to its
      unique interactions with flap residues. This structure also explains why the I50L
      and I84V mutations are important in decreasing the binding affinity of
      atazanavir.

PMID- 16634629
TI  - Component interactions and implications for complex formation in the
      multicomponent toluene 4-monooxygenase.
AB  - A fluorophore-labeled form of the T4moD, the catalytic effector protein of the
      toluene 4-monooxygenase complex, was prepared by engineering the N-terminal
      region to contain a tetraCys motif and treatment with biarsenical fluorescein.
      Fluorescence anisotropy was used to study the protein-protein interactions among
      various combinations of the four components of the complex. Binding interactions
      were detected between T4moD and the hydroxylase component T4moH [K(D) value of 83
      nM for interaction with the alphabetagamma protomer] and between T4moD and the
      Rieske [2Fe-2S] ferredoxin component T4moC (K(D) value of 78 nM). No binding
      interactions were detected between T4moD and the NADH oxidoreductase component
      T4moF, but T4moF was able to disrupt binding between T4moC and T4moD. The
      detected binding interactions suggest an intermediary electron transfer complex
      between T4moC and T4moD that excludes T4moF. The results indicate that
      specialization of effector protein function may include specific protein-protein
      interactions with [2Fe-2S] domains as well as the hydroxylase component.

PMID- 16634630
TI  - Unstructured RNA is a substrate for tRNase Z.
AB  - tRNase Z, which exists in almost all cells, is believed to be working primarily
      for tRNA 3' maturation. In Escherichia coli, however, the tRNase Z gene appears
      to be dispensable under normal growth conditions, and its physiological role is
      not clear. Here, to investigate a possibility that E. coli tRNase Z cleaves RNAs
      other than pre-tRNAs, we tested several unstructured RNAs for cleavage.
      Surprisingly, all these substrates were cleaved very efficiently at multiple
      sites by a recombinant E. coli enzyme in vitro. tRNase Zs from Bacillus subtilis
      and Thermotoga maritima also cleaved various unstructured RNAs. The E. coli and
      B. subtilis enzymes seem to have a tendency to cleave after cytidine or before
      uridine, while cleavage by the T. maritima enzyme inevitably occurred after CCA
      in addition to the other cleavages. Assays to determine optimal conditions
      indicated that metal ion requirements differ between B. subtilis and T. maritima
      tRNase Zs. There was no significant difference in the observed rate constant
      between unstructured RNA and pre-tRNA substrates, while the K(d) value of a
      tRNase Z/unstructured RNA complex was much higher than that of an enzyme/pre-tRNA
      complex. Furthermore, eukaryotic tRNase Zs from yeast, pig, and human cleaved
      unstructured RNA at multiple sites, but an archaeal tRNase Z from Pyrobaculum
      aerophilum did not.

PMID- 16634631
TI  - Mechanism of presynaptic filament stabilization by the bacteriophage T4 UvsY
      recombination mediator protein.
AB  - UvsY is the recombination mediator protein (RMP) of bacteriophage T4, which
      promotes homologous recombination by facilitating presynaptic filament assembly.
      The results of previous studies suggest that UvsY promotes the assembly of
      presynaptic filaments in part by stabilizing interactions between T4 UvsX
      recombinase and single-stranded DNA (ssDNA). To test this hypothesis, we studied
      the interactions of UvsX and UvsY with a fluorescein-derivatized oligonucleotide.
      This assay distinguishes between bipartite UvsX- or UvsY-ssDNA and tripartite
      UvsX-UvsY-ssDNA complex formation via differential fluorescence quenching
      effects. Salt stabilities of the three complexes were measured at equilibrium in
      the presence and absence of various nucleotide ligands of the UvsX protein and
      also under steady-state conditions for UvsX-catalyzed ssDNA-dependent ATP
      hydrolysis. The results demonstrate that UvsY globally stabilizes UvsX-ssDNA
      complexes, consistent with an increase in the apparent equilibrium binding
      affinity, K(ss)omega, of the UvsX-ssDNA interactions. The UvsY-mediated affinity
      increase is observed at equilibrium in the presence of ADP, ATPgammaS, or in the
      absence of the nucleotide and also at steady-state in the presence of ATP.
      Intriguingly, the stabilizing effects of UvsY and ATPgammaS on UvsX-ssDNA
      interactions are synergistic, indicating nonredundant mechanisms for UvsX-ssDNA
      complex stabilization by RMP versus nucleoside triphosphate effectors.
      Experiments with UvsY missense mutants defective in ssDNA binding demonstrate
      that UvsY-ssDNA interactions are of major importance in stabilizing UvsX-ssDNA
      complexes, whereas UvsY-UvsX protein-protein interactions provide residual
      stabilization energy. Together, the data is consistent with a mechanism in which
      UvsY stabilizes presynaptic filaments by organizing the ssDNA lattice into a
      structure that is favorable for UvsX-ssDNA interactions.

PMID- 16634632
TI  - Inhibitors of amyloid toxicity based on beta-sheet packing of Abeta40 and
      Abeta42.
AB  - Amyloid fibrils associated with Alzheimer's disease and a wide range of other
      neurodegenerative diseases have a cross beta-sheet structure, where main chain
      hydrogen bonding occurs between beta-strands in the direction of the fibril axis.
      The surface of the beta-sheet has pronounced ridges and grooves when the
      individual beta-strands have a parallel orientation and the amino acids are in
      register with one another. Here we show that in Abeta amyloid fibrils, Met35
      packs against Gly33 in the C-terminus of Abeta40 and against Gly37 in the C
      terminus of Abeta42. These packing interactions suggest that the protofilament
      subunits are displaced relative to one another in the Abeta40 and Abeta42 fibril
      structures. We take advantage of this corrugated structure to design a new class
      of inhibitors that prevent fibril formation by placing alternating glycine and
      aromatic residues on one face of a beta-strand. We show that peptide inhibitors
      based on a GxFxGxF framework disrupt sheet-to-sheet packing and inhibit the
      formation of mature Abeta fibrils as assayed by thioflavin T fluorescence,
      electron microscopy, and solid-state NMR spectroscopy. The alternating large and
      small amino acids in the GxFxGxF sequence are complementary to the corresponding
      amino acids in the IxGxMxG motif found in the C-terminal sequence of Abeta40 and
      Abeta42. Importantly, the designed peptide inhibitors significantly reduce the
      toxicity induced by Abeta42 on cultured rat cortical neurons.

PMID- 16634633
TI  - Structural features in EIAV NCp11: a lentivirus nucleocapsid protein with a short
      linker.
AB  - Lentiviral nucleocapsid proteins are a class of multifunctional proteins that
      play an essential role in RNA packaging and viral infectivity. They contain two
      CX(2)CX(4)HX(4)C zinc binding motifs connected by a basic linker of variable
      length. The 3D structure of a 37-aa peptide corresponding to sequence 22-58 from
      lentiviral EIAV nucleocapsid protein NCp11, complexed with zinc, has been
      determined by 2D (1)H NMR spectroscopy, simulated annealing, and molecular
      dynamics. The solution structure consists of two zinc binding domains held
      together by a five-residue basic linker Arg(38)-Ala-Pro-Lys-Val(42) that allows
      for spatial proximity between the two finger domains. Observed linker folding is
      stabilized by H bonded secondary structure elements, resulting in an Omega-shaped
      central region, asymmetrically centered on the linker. The conformational
      differences and similarities with other NC zinc binding knuckles have been
      systematically analyzed. The two CCHC motifs, both characterized by a peculiar
      Pro-Gly sequence preceding the His residue, although preserving Zn-binding
      geometry and chirality of other known NC proteins, exhibit local fold differences
      both between each other and in comparison with other previously characterized
      retroviral CCHC motifs.

PMID- 16634634
TI  - Hyperphosphorylation of tau induces local polyproline II helix.
AB  - Alzheimer's disease is characterized by two protein precipitates, extracellular
      amyloid plaques and intracellular neurofibrillary tangles (NFTs). The primary
      constituent of NFTs is a hyperphosphorylated form of the microtubule-binding
      protein tau. Hyperphosphorylation of tau on over 30 residues, primarily within
      proline-rich sequences, is associated with conformational changes whose nature is
      poorly defined. Peptides derived from the proline-rich region of tau (residues
      174-242) were synthesized, and the conformations were analyzed for the
      nonphosphorylated and phosphorylated peptides. CD and NMR data indicate that
      phosphorylation of serine and threonine residues in proline-rich sequences
      induces a conformational change to a type II polyproline helix. The largest
      phosphorylation-dependent conformational changes observed by CD were for tau
      peptides incorporating residues 174-183 or residues 229-238. Phosphoserine and
      phosphothreonine residues exhibited ordered values of (3)J(alphaN) (3.1-6.2 Hz;
      mean = 4.7 Hz) compared to nonphosphorylated serine and threonine.
      Phosphorylation of a tau peptide consisting of tau residues 196-209 resulted in
      the disruption of a nascent alpha-helix. These results suggest that global
      reorganization of tau may occur upon hyperphosphorylation of proline-rich
      sequences in tau.

PMID- 16634635
TI  - Conformational states and dynamics of rhodopsin in micelles and bilayers.
AB  - Nitroxide sensors were placed in rhodopsin at sites 140, 227, 250, and 316 to
      monitor the dynamics and conformation of the receptor at the cytoplasmic surface
      in solutions of dodecyl maltoside (DM), digitonin, and phospholipid bilayers of
      two compositions. The EPR spectra reveal a remarkable similarity of rhodopsin
      structure and the activating conformational change in DM and bilayers, the
      hallmark of which is an outward tilt of transmembrane helix VI. This
      conformational change is blocked in solutions of digitonin, although changes in
      optical absorbance accompany activation, showing that absorbance and structural
      changes are not necessarily coupled. In DM and bilayers, the receptor is
      apparently in equilibrium between conformational substates whose populations are
      modulated by activation. Despite the general similarity in the two environments,
      the receptor conformations have increased flexibility in DM relative to bilayers.
      For the activated receptor in DM and bilayers, a pH-dependent conformational
      equilibrium is identified that may correspond to the optically characterized
      MII(a)()-MII(b)() equilibrium. No specific effects of headgroup composition on
      receptor conformation in lipid bilayers were found.

PMID- 16634636
TI  - The achondroplasia mutation does not alter the dimerization energetics of the
      fibroblast growth factor receptor 3 transmembrane domain.
AB  - The Gly380 --> Arg mutation in the TM domain of fibroblast growth factor receptor
      3 (FGFR3) of the RTK family is linked to achondroplasia, the most common form of
      human dwarfism. The molecular mechanism of pathology induction is under debate,
      and two different mechanisms have been proposed to contribute to pathogenesis:
      (1) Arg380-mediated FGFR3 dimer stabilization and (2) slow downregulation of the
      activated mutant receptors. Here we show that the Gly380 --> Arg mutation does
      not alter the dimerization energetics of the FGFR3 transmembrane domain in
      detergent micelles or in lipid bilayers. This result indicates that pathogenesis
      in achondroplasia cannot be explained simply by a higher dimerization propensity
      of the mutant FGFR3 TM domain, thus highlighting the importance of the observed
      slow downregulation in phenotype induction.

PMID- 16634637
TI  - CopH from Cupriavidus metallidurans CH34. A novel periplasmic copper-binding
      protein.
AB  - The copH gene is one of the 19 open reading frames (ORFs) found in the cop
      cluster borne by the large plasmid pMol30 in Cupriavidus metallidurans CH34. The
      entire cluster is involved in detoxification of copper from the cytoplasm as well
      as from the periplasm. The function of the corresponding protein, CopH, is not
      yet clear, but it seems to be involved in the late response phase. We have cloned
      copH and overproduced and purified the corresponding protein. CopH is rather
      unique as only one paralog can be found in the databases. It is a dimeric protein
      with a molecular mass of 13 200 Da per subunit and located in the periplasm. The
      metal binding properties of CopH were examined by using a series of techniques
      such as UV-visible spectroscopy, circular dichroism (CD), electron paramagnetic
      resonance (EPR), surface plasmon resonance (SPR), mass spectrometry, and nuclear
      magnetic resonance (NMR). All together, the corresponding data are consistent
      with a dimeric protein containing one metal-binding site per subunit. These sites
      have a high affinity for Cu(II) but can also bind zinc or nickel. CopH does not
      contain any cysteines or methionines but contains two histidines. EPR and UV
      visible features are consistent with the presence of Cu(II) type 2 centers in a
      nitrogen ligand field. SPR data confirm the involvement of the histidine residues
      in copper binding. CD and NMR data reveal that CopH is partially unfolded.

PMID- 16634638
TI  - Peptide binding and NMR analysis of the interaction between SAP97 PDZ2 and GluR
      A: potential involvement of a disulfide bond.
AB  - Synaptic delivery of GluR-A (GluR1) subunit-containing glutamate receptors
      depends on a C-terminal type I PDZ binding motif in GluR-A. Synapse-associated
      protein 97 (SAP97) is the only PDZ domain protein known to associate with GluR-A.
      We have used NMR spectroscopy and a biotinylated peptide binding assay to
      characterize the interaction between synthetic GluR-A C-terminal peptides and the
      PDZ2 domain of SAP97 (SAP97(PDZ2)), previously determined to be the dominant
      factor responsible for the interaction. The binding mode appeared to be strongly
      influenced by redox conditions. Chemical shift changes observed in NMR spectra
      indicate that under reducing conditions, the last four residues of GluR-A
      peptides bind to PDZ2 in a fashion typical of class I PDZ interactions. The
      binding is weak and relatively nonselective as it occurs similarly with a PDZ2
      domain derived from PSD-95, a related protein not believed to directly interact
      with GluR-A. In the absence of reducing agents, conserved cysteine residues in
      SAP97(PDZ2) and the GluR-A C-terminus gave rise to an anomalous behavior in a
      microplate assay with a biotinylated GluR-A 18-mer peptide. A covalent disulfide
      linked complex between SAP97(PDZ2) and the GluR-A peptide was seen in the binding
      assay and in the NMR experiments performed under oxidizing conditions. The
      results are consistent with a two-step binding mechanism consisting of an initial
      PDZ interaction followed by stabilization of the complex by a disulfide bond. The
      possible physiological relevance of redox regulation of SAP97-GluR-A interaction
      remains to be established.

PMID- 16634639
TI  - Thermodynamics of statherin adsorption onto hydroxyapatite.
AB  - Statherin is a salivary protein that inhibits the nucleation and growth of
      hydroxyapatite crystals in the supersaturated environment of the oral cavity. The
      thermodynamics of adsorption of statherin onto hydroxyapatite crystals have been
      characterized here by isothermal titration calorimetry and equilibrium adsorption
      isotherm analysis. At 25 degrees C, statherin adsorption is characterized by an
      exothermic enthalpy of approximately 3 kcal/mol that diminishes to zero at
      approximately 25% surface coverage. The initial heat of statherin adsorption
      increases with temperature, displaying a positive heat capacity change of 194 +/-
      7 cal K(-)(1) mol(-)(1) at 25 degrees C. The heat of adsorption during this
      initial phase is strongly dependent on the buffer species, and from the
      differential heats of buffer ionization, it can be calculated that approximately
      one proton is taken up by the crystal or protein upon adsorption. The free energy
      of adsorption is dominated at all coverages by a large positive entropy (>or=23
      cal K(-)(1) mol(-)(1)), which may be partially due to the loss of organized water
      that hydrates the protein and the mineral surface prior to adsorption. These
      results are interpreted using a two-site model for adsorption of statherin onto
      the hydroxyapatite crystals.

PMID- 16634640
TI  - r-VKORC1 expression in factor IX BHK cells increases the extent of factor IX
      carboxylation but is limited by saturation of another carboxylation component or
      by a shift in the rate-limiting step.
AB  - Carboxylation of vitamin K-dependent (VKD) proteins is required for their
      activity and depends on reduced vitamin K generated by vitamin K oxidoreductase
      (VKOR) and a redox protein that regenerates VKOR activity. VKD protein
      carboxylation is inefficient in mammalian cells, and to understand why
      carboxylation becomes saturated, we developed an approach that directly measures
      the extent of intracellular VKD protein carboxylation. Analysis of factor IX
      (fIX)-expressing BHK cells indicated that slow egress of fIX from the endoplasmic
      reticulum and preferential secretion of the carboxylated form contribute to
      secreted fIX being more fully carboxylated. The analysis also revealed the first
      reported in vivo VKD protein turnover, which was 14-fold faster than that which
      occurs in vitro, suggesting facilitation of this process in vivo. r-VKORC1
      expression increased the rate of fIX carboxylation and the extent of secreted
      carboxylated fIX approximately 2-fold, which shows that carboxylation is the rate
      limiting step in fIX turnover and which was surprising because turnover in vitro
      is limited by release of carboxylated fIX. Interestingly, the increases were
      significantly smaller than the amount of VKOR overexpression (15-fold). However,
      when cell extracts were tested in single-turnover experiments in vitro, where
      redox protein is functionally substituted with dithiothreitol, VKOR
      overexpression increased the fIX carboxylation rate 14-fold, showing r-VKORC1 is
      functional for supporting fIX carboxylation. These data indicate that the effect
      of VKOR overexpression is limited in vivo, possibly because a carboxylation
      component like the redox protein becomes saturated or because another step is now
      rate-limiting. The studies illustrate the complexity of carboxylation and
      potential importance of component stoichiometry to overall efficiency.

PMID- 16634641
TI  - Tyrosine phosphorylation is required for functional activation of disulfide
      containing constitutively active STAT mutants.
AB  - Aberrant activation of STAT transcription factors has been implicated in a
      variety of cancers. Constitutively active forms of STAT1 and STAT3 (STAT1C and
      STAT3C) have been developed to determine the effects of STAT activation in
      isolation from other cytokine-stimulated signaling pathways. These mutants were
      created by engineering cysteine residues into the carboxy terminus of each STAT
      molecule, allowing a hypothesized disulfide bond to form between two
      unphosphorylated monomers. To determine whether the presence of cysteine residues
      is sufficient to allow for functional activation in the absence of tyrosine
      phosphorylation, we developed STAT1C and STAT3C mutants that are unable to be
      phosphorylated on the critical tyrosine residue. Without the tyrosine residue,
      cysteine containing constitutive STAT mutants failed to transactivate STAT target
      genes. Furthermore, transfection of STAT dominant negative mutants prevented the
      activation of STAT1C and STAT3C. Cytokine-induced activation of STAT1C and STAT3C
      was dramatically prolonged when compared to wild-type proteins and led to
      extended STAT-dependent gene activation. These data show that tyrosine
      phosphorylation is required for activation of STAT1C and STAT3C. Additionally,
      these findings suggest the existence of basal phosphorylation that is a dynamic
      process that involves both phosphorylation and dephosphorylation. The
      constitutive STAT mutants likely show heightened activity because of the cysteine
      residues stabilizing these dimers and preventing dephosphorylation, resulting in
      the accumulation of trancriptionally active STAT dimer complexes.

PMID- 16634642
TI  - Mutations of CB1 T210 produce active and inactive receptor forms: correlations
      with ligand affinity, receptor stability, and cellular localization.
AB  - Human cannabinoid receptor 1 (CB(1)) has attracted substantial interest as a
      potential therapeutic target for treating obesity and other obsessive disorders.
      An understanding of the mechanism governing the transition of the CB(1) receptor
      between its inactive and active states is critical for understanding how
      therapeutics can selectively regulate receptor activity. We have examined the
      importance of the Thr at position 210 in CB(1) in this transition, a residue
      predicted to be on the same face of the helix as the Arg of the DRY motif highly
      conserved in the G protein-coupled receptor superfamily. This Thr was substituted
      with Ile and Ala via mutagenesis, and the receptors, T210I and T210A, were
      expressed in HEK 293 cells. The T210I receptor exhibited enhanced agonist and
      diminished inverse agonist affinity relative to the wild type, consistent with a
      shift toward the active form. However, treatment with GTPgammaS to inhibit G
      protein coupling diminished the affinity change for the inverse agonist
      SR141716A. The decreased thermal stability of the T210I receptor and increased
      level of internalization of a T210I receptor-GFP chimera were also observed,
      consistent with constitutive activity. In contrast, the T210A receptor exhibited
      the opposite profile: diminished agonist and enhanced inverse agonist affinity.
      The T210A receptor was found to be more thermally stable than the wild type, and
      high levels of a T210A receptor-GFP chimera were localized to the cell surface as
      predicted for an inactive receptor form. These results suggest that T210 plays a
      key role in governing the transition between inactive and active CB(1) receptor
      states.

PMID- 16634643
TI  - Substrate-assisted cysteine deprotonation in the mechanism of dimethylargininase
      (DDAH) from Pseudomonas aeruginosa.
AB  - The enzyme dimethylargininase (also known as dimethylarginine
      dimethylaminohydrolase or DDAH; EC 3.5.3.18) catalyzes the hydrolysis of
      endogenous nitric oxide synthase inhibitors, N(omega)-methyl-l-arginine and
      N(omega),N(omega)-dimethyl-l-arginine. Understanding the mechanism and regulation
      of DDAH activity is important for developing ways to control nitric oxide
      production during angiogenesis and in many cases of vascular endothelial
      pathobiology. Several possible physiological regulation mechanisms of DDAH depend
      upon the presence of an active-site cysteine residue, Cys249 in Pseudomonas
      aeruginosa (Pa) DDAH, which is proposed to serve as a nucleophile in the
      catalytic mechanism. Through the use of pH-dependent ultraviolet and visible (UV
      vis) difference spectroscopy and inactivation kinetics, the pK(a) of the active
      site Cys249 in the resting enzyme was found to be unperturbed from pK(a) values
      of typical noncatalytic cysteine residues. In contrast, the pH dependence of
      k(cat) values indicates a much lower apparent pK(a) value. UV-vis difference
      spectroscopy between wild-type and C249S DDAH shows absorbance changes consistent
      with Cys249 deprotonation to the anionic thiolate upon binding positively charged
      ligands. The proton from Cys249 is lost either to the solvent or to an
      unidentified general base. A mutation of the active-site histidine residue,
      H162G, does not eliminate cysteine nucleophilicity, further arguing against a pre
      formed ion pair with Cys249. Finally, UV-vis and X-ray absorption spectroscopy
      revealed that inhibitory metal ions can bind at these two active-site residues,
      Cys249 and His162, and also stabilize the anionic form of Cys249. These results
      support a proposed substrate-assisted mechanism for Pa DDAH in which ligand
      binding modulates the reactivity of the active-site cysteine.

PMID- 16634644
TI  - Raman evidence for specific substrate-induced structural changes in the heme
      pocket of human cytochrome P450 aromatase during the three consecutive oxygen
      activation steps.
AB  - Specific substrate-induced structural changes in the heme pocket are proposed for
      human cytochrome P450 aromatase (P450arom) which undergoes three consecutive
      oxygen activation steps. We have experimentally investigated this heme
      environment by resonance Raman spectra of both substrate-free and substrate-bound
      forms of the purified enzyme. The Fe-CO stretching mode (nu(Fe)(-)(CO)) of the CO
      complex and Fe(3+)-S stretching mode (nu(Fe)(-)(S)) of the oxidized form were
      monitored as a structural marker of the distal and proximal sides of the heme,
      respectively. The nu(Fe)(-)(CO) mode was upshifted from 477 to 485 and to 490 cm(
      )(1) by the binding of androstenedione and 19-aldehyde-androstenedione,
      substrates for the first and third steps, respectively, whereas nu(Fe)(-)(CO) was
      not observed for P450arom with 19-hydroxyandrostenedione, a substrate for the
      second step, indicating that the heme distal site is very flexible and changes
      its structure depending on the substrate. The 19-aldehyde-androstenedione binding
      could reduce the electron donation from the axial thiolate, which was evident
      from the low-frequency shift of nu(Fe)(-)(S) by 5 cm(-)(1) compared to that of
      androstenedione-bound P450arom. Changes in the environment in the heme distal
      site and the reduced electron donation from the axial thiolate upon 19-aldehyde
      androstenedione binding might stabilize the ferric peroxo species, an active
      intermediate for the third step, with the suppression of the formation of
      compound I (Fe(4+)=O porphyrin(+)(*)) that is the active species for the first
      and second steps. We, therefore, propose that the substrates can regulate the
      formation of alternative reaction intermediates by modulating the structure on
      both the heme distal and proximal sites in P450arom.

PMID- 16634645
TI  - Redox titration of all electron carriers of cytochrome c oxidase by Fourier
      transform infrared spectroscopy.
AB  - Electrochemical redox titrations of cytochrome c oxidase from Paraccocus
      denitrificans were performed by attenuated total reflectance Fourier transform
      infrared (ATR-FTIR) spectroscopy. The majority of the differential infrared
      absorption features may be divided into four groups, which correlate with the
      redox transitions of the four redox centers of the enzyme. Infrared spectroscopy
      has the advantage of allowing one to measure independent alterations in redox
      centers, which are not well separated, or even observed, by other spectroscopic
      techniques. We found 12 infrared bands that titrated with the highest observed
      midpoint redox potential (E(m) = 412 mV at pH 6.5) and which had a pH dependence
      of 52 mV per pH unit in the alkaline region. These bands were assigned to be
      linked to the Cu(B) center. We assigned bands to the Cu(A) center that showed a
      pH-independent E(m) of 250 mV. Two other groups of infrared differential bands
      reflected redox transitions of the two heme groups and showed a more complex
      behavior. Each of them included two parts, corresponding to high- and low
      potential redox transitions. For the bands representing heme a, the ratio of high
      to low-potential components was ca. 3:2; for heme a(3) this ratio was ca. 2:3.
      Taking into account the redox interactions between the hemes, these ratios
      yielded a difference in E(m) of 9 mV between the hemes (359 mV for heme a; 350 mV
      for heme a(3) at pH 8.0). The extent of the redox interaction between the hemes (
      115 mV at pH 8.0) was found to be pH-dependent. The pH dependence of the E(m)
      values for the two hemes was the same and about two times smaller than the
      theoretical one, suggesting that an acid/base group binds a proton upon reduction
      of either heme. The applied approach allowed assignment of infrared bands in each
      of the four groups to vibrations of the hemes, ligands of the redox centers,
      amino acid residues, and/or protein backbone. For example, the well-known band
      shift at 1737/1746 cm(-)(1) corresponding to the protonated glutamic acid E278
      correlated with oxidoreduction of heme a.

PMID- 16634646
TI  - Uncoupling of electron and proton transfers in the photocycle of bacterial
      reaction centers under high light intensity.
AB  - Photosynthetic reaction centers produce and export oxidizing and reducing
      equivalents in expense of absorbed light energy. The formation of fully reduced
      quinone (quinol) requires a strict (1:1) stoichiometric ratio between the
      electrons and H(+) ions entering the protein. The steady-state rates of both
      transports were measured separately under continuous illumination in the reaction
      center from the photosynthetic bacterium Rhodobacter sphaeroides. The uptake of
      the first proton was retarded by different methods and made the rate-limiting
      reaction in the photocycle. As expected, the rate constant of the observed proton
      binding remained constant (7 s(-)(1)), but that of the cytochrome photooxidation
      did show a remarkably large increase from 14 to 136 s(-)(1) upon increase of the
      exciting light intensity up to 5 W/cm(2) (808 nm) at pH 8.4 in the presence of
      NiCl(2). This corresponds to about 20:1 (e(-):H(+)) stoichiometric ratio. The
      observed enhancement is linearly proportional to the light intensity and the rate
      constant of the proton uptake by the acceptor complex and shows saturation
      character with quinone availability. For interpretation of the acceleration of
      cytochrome turnover, an extended model of the photocycle is proposed. A fraction
      of photochemically trapped RC can undergo fast (>10(3) s(-)(1)) conformational
      change where the semiquinone loses its high binding affinity (the dissociation
      constant increases by more than 5 orders of magnitude) and dissociates from the
      Q(B) binding site of the protein with a high rate of 4000 s(-)(1). Concomitantly,
      superoxide is being produced. No H(+) ion is taken up, and no quinol is created
      by the photocycle which is operating in about 25% of the reaction centers at the
      highest light intensity (5500 s(-)(1)) and slowest proton uptake (3.5 s(-)(1))
      used in our experiments. The possible physical background of the light-induced
      conformational change and the relationship between the energies of dissociation
      and redox changes of the quinone in the Q(B) binding sites are discussed.

PMID- 16634647
TI  - Lipid-specific membrane activity of human beta-defensin-3.
AB  - Defensins represent a major component of innate host defense against bacteria,
      fungi, and enveloped viruses. One potent defensin found, e.g., in epithelia, is
      the polycationic human beta-defensin-3 (hBD3). We investigated the role of the
      lipid matrix composition, and in particular the presence of negatively charged
      lipopolysaccharides (LPS) from sensitive (Escherichia coli, Salmonella enterica
      serovar Minnesota) or resistant (Proteus mirabilis) Gram-negative bacteria or of
      the zwitterionic phospholipids of human cells, in determining the action of
      polycationic hBD3 on the different membranes, and related to their biological
      activity. The main focus was directed on data derived from electrical
      measurements on a reconstitution system of the OM as a planar asymmetric bilayer
      composed on one side of LPS and on the other of a phospholipid mixture. Our
      results demonstrate that the antimicrobial activity and the absence of
      cytotoxicity can be explained by the lipid-specificity of the peptide. A clear
      correlation between these aspects of the biological activity of hBD3 and its
      interaction with lipid matrices could be found. In particular, hBD3 could only
      induce lesions in those membranes resembling the lipid composition of the OM of
      sensitive bacterial strains. The permeation through the membrane is a decisive
      first step for the biological activity of many antimicrobial peptides. Therefore,
      we propose that the lipid-specificity of hBD3 as well as some other membrane
      active antimicrobial peptides is important for their activity against bacteria or
      mammalian cells.

PMID- 16634648
TI  - Purification of a human SRCAP complex that remodels chromatin by incorporating
      the histone variant H2A.Z into nucleosomes.
AB  - The Snf-2-related CREB-binding protein activator protein (SRCAP) serves as a
      coactivator for a number of transcription factors known to interact with CBP.
      Swr1, the closest Saccharomyces cerevisiae ortholog of SRCAP, is a component of
      the chromatin remodeling complex SWR-C, which catalyzes exchange of the histone
      variant H2A.Z into nucleosomes. In this report, we use a combination of
      conventional chromatography and anti-SRCAP immunoaffinity chromatography to
      purify a native human SRCAP complex with a polypeptide composition similar to
      that of SWR-C, and we show for the first time that this SRCAP-containing complex
      supports ATP-dependent exchange of histone dimers containing H2B and H2A.Z into
      mononucleosomes reconstituted with recombinant H2A, H2B, H3, and H4. Our
      findings, together with previous evidence implicating H2A.Z in transcriptional
      regulation, suggest that SRCAP's coactivator function may depend on its ability
      to promote incorporation of H2A.Z into chromatin.

PMID- 16634649
TI  - Dihydroquinone ansamycins: toward resolving the conflict between low in vitro
      affinity and high cellular potency of geldanamycin derivatives.
AB  - Heat shock protein 90 (Hsp90) is critical for the maturation of numerous client
      proteins, many of which are involved in cellular transformation and oncogenesis.
      The ansamycins, geldanamycin (GA) and its derivative, 17-allylaminogeldanamycin
      (17-AAG), inhibit Hsp90. As such, the prototypical Hsp90 inhibitor, 17-AAG, has
      advanced into clinical oncology trials. GA and 17-AAG potently inhibit tumor cell
      proliferation and survival but have been reported to bind weakly to Hsp90 in
      vitro. Recent studies have suggested that the in vitro potency of ansamycins
      against Hsp90 may be enhanced in the presence of cochaperones. Here, we present
      evidence of an alternative explanation. Ansamycins reduced to their
      dihydroquinones in the presence of common reducing agents in vitro have
      approximately 40-fold greater affinity than the corresponding oxidized quinones.
      The dihydroquinone of 17-AAG is not generated in an aqueous environment in the
      absence of reducing agents but is produced in both tumor and normal quiescent
      epithelial cells. The reduced form of 17-AAG is differentiated from its oxidized
      form not only by the higher affinity for Hsp90 but also by a protracted K(off)
      rate. Therefore, the in vivo accumulation of the high-affinity dihydroquinone
      ansamycins in tumor cells contributes to the antitumor activity of these
      compounds and alters our understanding of the active species driving the efficacy
      of this class of compounds.

PMID- 16634652
TI  - Water as a cofactor in the unidirectional light-driven proton transfer steps in
      bacteriorhodopsin.
AB  - Recent evidence for involvement of internal water molecules in the mechanism of
      bacteriorhodopsin is reviewed. Water O-H stretching vibration bands in the
      Fourier transform IR difference spectra of the L, M and N intermediates of
      bacteriorhodopsin were analyzed by photoreactions at cryogenic temperatures. A
      broad vibrational band in L was shown to be due to formation of a structure of
      water molecules connecting the Schiff base to the Thr46-Asp96 region. This
      structure disappears in the M intermediate, suggesting that it is involved in
      transient stabilization of the L intermediate prior to proton transfer from the
      Schiff base to Asp85. The interaction of the Schiff base with a water molecule is
      restored in the N intermediate. We propose that water is a critical mobile
      component of bacteriorhodopsin, forming organized structures in the transient
      intermediates during the photocycle and, to a large extent, determining the
      chemical behavior of these transient states.

PMID- 16634654
TI  - Rhesus macaques (Macaca mulatta) monitor uncertainty during numerosity judgments.
AB  - Two rhesus macaques (Macaca mulatta) judged arrays of dots on a computer screen
      as having more or fewer dots than a center value that was never presented in
      trials. After learning a center value, monkeys were given an uncertainty response
      that let them decline to make the numerosity judgment on that trial. Across
      center values (3-7), errors occurred most often for sets adjacent in numerosity
      to the center value. The monkeys also used the uncertainty response most
      frequently on these difficult trials. A 2nd experiment showed that monkeys'
      responses reflected numerical magnitude and not the surface-area illumination of
      the displays. This research shows that monkeys' uncertainty-monitoring capacity
      extends to the domain of numerical cognition. It also shows monkeys' use of the
      purest uncertainty response possible, uncontaminated by any secondary motivator.

PMID- 16634655
TI  - The role of reference points in ordinal numerical comparisons by rhesus macaques
      (Macaca mulatta).
AB  - Two experiments examined ordinal numerical knowledge in rhesus macaques (Macaca
      mulatta). Experiment 1 replicated the finding (E. M. Brannon & H. S. Terrace,
      2000) that monkeys trained to respond in descending numerical order (4-->3-->2-
      >1) did not generalize the descending rule to the novel values 5-9 in contrast to
      monkeys trained to respond in ascending order. Experiment 2 examined whether the
      failure to generalize a descending rule was due to the direction of the training
      sequence or to the specific values used in the training sequence. Results
      implicated 3 factors that characterize a monkey's numerical comparison process:
      Weber's law, knowledge of ordinal direction, and a comparison of each value in a
      test pair with the reference point established by the first value of the training
      sequence.

PMID- 16634656
TI  - Deepened extinction from compound stimulus presentation.
AB  - Three experiments with rats and 2 with pigeons explored the effect of presenting
      2 extinguished excitatory stimuli in compound. Four learning situations were
      used: Pavlovian magazine approach, Pavlovian fear conditioning, and instrumental
      discriminative instrumental learning in rats, as well as Pavlovian sign tracking
      in pigeons. All 5 experiments confirmed D. Reberg's (1972) observation that even
      after extinction of the individual stimuli, presenting them in compound evoked
      substantial responding. Moreover, nonreinforcement of that compound deepened
      extinction of an element more substantially than did additional presentation of
      that element alone. Such compound exposure reduced spontaneous recovery, reduced
      reinstatement, and slowed subsequent reconditioning. The primary determinant
      seemed to be the enhanced associative strength rather than the enhanced
      conditioned responding that occurred during the nonreinforced compound.

PMID- 16634657
TI  - Associative activation of stimulus representations restores lost salience:
      implications for perceptual learning.
AB  - In 3 experiments, rats received preexposure to presentations of a compound flavor
      BX. The effective salience of B was then tested by assessing its ability to
      interfere with the aversion controlled by another flavor or the tendency to drink
      a saline solution after the induction of a salt need. It was found that the
      effective salience of B was maintained when during preexposure, presentations of
      BX alternated with presentations of X alone. This was true both when BX was
      presented as a simultaneous compound (Experiment 1) and as a serial compound (X-
      >B; Experiments 2 and 3); salience was not maintained when the serial compound
      took the form B-->X (Experiments 2 and 3a). It was argued that the salience of B
      declines during preexposure but is restored when presentations of X are able to
      activate the representation of B by way of the associative X-B link.

PMID- 16634658
TI  - Associative sequence learning in humans.
AB  - In a series of experiments using the serial reaction time paradigm, the authors
      compared the predictions of a powerful associative model of sequence learning
      (the simple recurrent network; J. L. Elman, 1990) with human performance on the
      problem devised by A. Maskara and W. Noetzel (1993). Even though the predictions
      made by the simple recurrent network for variants of this problem are often
      counterintuitive, they matched human performance closely, suggesting that
      performance was associatively based rather than rule based. Simple associative
      chaining models of sequence learning, however, have difficulty in accommodating
      these results. The authors' conclusion is that, under the conditions of the
      experiments, human sequence learning is associatively driven, as long as this is
      understood to mean that a sufficiently powerful means of extracting the
      statistical regularities in the sequences is in play.

PMID- 16634659
TI  - A short intertrial interval facilitates acquisition of context-conditioned fear
      and a short retention interval facilitates its expression.
AB  - Rats were shocked in a context on two occasions and then tested for fear
      reactions as indexed by freezing. Rats spent the interval between conditioning
      trials and between conditioning and test in their home cages. A short interval
      between context-conditioning trials or between trials involving a discrete
      conditioned stimulus (CS) produced better learning than longer intervals. A short
      retention interval between conditioning and test produced better performance than
      longer intervals. The effects of the intertrial interval on learning are the
      opposite of those reported previously and are opposite to those predicted by
      contemporary learning theories. The effects of the training to test interval on
      performance are predicted by Wagner's sometimes opponent process (SOP) theory
      (Wagner, 1981).

PMID- 16634660
TI  - Enhanced discrimination between flavor stimuli: roles of salience modulation and
      inhibition.
AB  - Rats were given intermixed preexposure to the compound flavors AX and BX and to
      the compound CX in a separate block of trials (4 presentations of each compound).
      In Experiment 1, rats showed less generalization of conditioned aversion from AX
      to BX than from CX to BX, a perceptual learning effect. Experiment 2 showed that
      the formation of an excitatory association proceeded more readily between A and B
      than between C and B, suggesting that intermixed preexposure maintains the
      effective salience of A and B and does not establish inhibition between them, a
      process that would require prolonged preexposure. According to this analysis,
      salience modulation and associative inhibition may contribute to perceptual
      learning at different stages of preexposure.

PMID- 16634661
TI  - Inhibitory associations contribute to perceptual learning in humans.
AB  - Perceptual learning in humans was examined in 2 experiments. In Experiment 1,
      participants received intermixed exposure to 2 similar compounds (AX, BX, AX, BX,
      . . .) and blocked exposure to a 2nd pair of similar compounds (CY, CY, . . . ,
      DY, DY, . . .). Aversions established to AX and CY generalized less to BX than to
      DY. In Experiment 2, 1 pair of compounds was presented in a forward order (i.e.,
      AX3BX), whereas the 2nd pair of compounds was presented in a backward order
      (i.e., DY-->CY). Aversions established to AX and CY generalized less to BX than
      to DY. These results indicate that inhibitory associations contribute to
      perceptual learning in humans and thereby establish a fundamental similarity
      between the mechanisms that underlie perceptual learning in humans and rats.

PMID- 16634662
TI  - Rhesus monkeys (Macaca mulatta) immediately generalize the uncertain response.
AB  - Rhesus monkeys (Macaca mulatta) have learned, like humans, to use an uncertain
      response adaptively under test conditions that create uncertainty, suggesting a
      metacognitive process by which human and nonhuman primates may monitor their
      confidence and alter their behavior accordingly. In this study, 4 rhesus monkeys
      generalized their use of the uncertain response, without additional training, to
      2 familiar tasks (2-choice discrimination learning and mirror-image matching to
      sample) that predictably and demonstrably produce uncertainty. The monkeys were
      significantly less likely to use the uncertain response on trials in which the
      answer might be known. These results indicate that monkeys, like humans, know
      when they do not know and that they can learn to use a symbol as a generalized
      means for indicating their uncertainty.

PMID- 16634663
TI  - Picture-object recognition in pigeons: evidence of representational insight in a
      visual categorization task using a complementary information procedure.
AB  - Success in tasks requiring categorization of pictorial stimuli does not prove
      that a subject understands what the pictures stand for. The ability to achieve
      representational insight is by no means a trivial one because it exceeds mere
      detection of 2-D features present in both the pictorial images and their
      referents. So far, evidence for such an ability in nonhuman species is weak and
      inconclusive. Here, the authors report evidence of representational insight in
      pigeons. After being trained on pictures of incomplete human figures, the birds
      responded significantly more to pictures of the previously missing parts than to
      nonrepresentative stimuli, which demonstrates that they actually recognized the
      pictures' representational content.

PMID- 16634664
TI  - Can lemurs learn to deceive? A study in the black lemur (Eulemur macaco).
AB  - Deceptive behavior in primates has been the focus of a number of studies.
      Nevertheless, such abilities have never been demonstrated in prosimians. The
      authors' goal was to analyze possible deception in lemurs according to a paradigm
      used with simians. Three black lemurs were trained to communicate about the
      location of a hidden reward with a cooperative trainer. Afterward, when a 2nd
      trainer and lemurs competed to gain access to the reward, each subject
      differentially adapted its learned behavior to the context. Their performances
      with the cooperative trainer remained stable while they showed various behavioral
      adjustments when faced to the competitive trainer: 1 subject refused to
      participate, another preferentially withheld information, and the 3rd sometimes
      pointed deceptively to obtain the reward.

PMID- 16634665
TI  - Once more: is beauty in the eye of the beholder? Relative contributions of
      private and shared taste to judgments of facial attractiveness.
AB  - Misconstruing the meaning of Cronbach's alpha, experts on facial attractiveness
      have conveyed the impression that facial-attractiveness judgment standards are
      largely shared. This claim is unsubstantiated, because information necessary for
      deciding whether judgments of facial attractiveness are more influenced by
      commonly shared or by privately held evaluation standards is lacking. Three
      experiments, using diverse face and rater samples to investigate the relative
      contributions of private and shared taste to judgments of facial attractiveness,
      are reported. These experiments show that for a variety of ancillary conditions,
      and contrary to the prevalent notion in the literature, private taste is about as
      powerful as shared taste. Important implications for scientific research strategy
      and laypeople's self-esteem are discussed.

PMID- 16634666
TI  - Imitative response tendencies following observation of intransitive actions.
AB  - Clear and unequivocal evidence shows that observation of object affordances or
      transitive actions facilitates the activation of a compatible response. By
      contrast, the evidence showing response facilitation following observation of
      intransitive actions is less conclusive because automatic imitation and spatial
      compatibility have been confounded. Three experiments tested whether observation
      of a finger movement (i.e., an intransitive action) in a choice reaction-time
      task facilitates the corresponding finger movement response because of imitation,
      a common spatial code, or some combination of both factors. The priming effects
      of a spatial and an imitative stimulus were tested in combination (Experiment 1),
      in opposition (Experiment 2), and independently (Experiment 3). Contrary to
      previous findings, the evidence revealed significant contributions from both
      automatic imitation and spatial compatibility, but the priming effects from an
      automatic tendency to imitate declined significantly across a block of trials
      whereas the effects of spatial compatibility remained constant or increased
      slightly. These differential effects suggest that priming associated with
      automatic imitation is mediated by a different regime than priming associated
      with spatial compatibility.

PMID- 16634667
TI  - On the surprising salience of curvature in grouping by proximity.
AB  - The authors conducted 3 experiments to explore the roles of curvature, density,
      and relative proximity in the perceptual organization of ambiguous dot patterns.
      To this end, they developed a new family of regular dot patterns that tend to be
      perceptually grouped into parallel contours, dot-sampled structured grids (DSGs).
      DSGs are similar to the dot lattices used to study grouping by proximity, except
      that only one of the potential organizations is rectilinear; the others are
      curvilinear. The authors used the method of M. Kubovy and J. Wagemans (1995) to
      study grouping by proximity in DSGs. They found that in the competition between
      the most likely organizations, one rectilinear and the other curvilinear, the
      latter is more salient. This phenomenon cannot be explained by contemporary
      accounts of grouping by proximity or contour integration.

PMID- 16634668
TI  - Memory for where, but not what, is used during visual search.
AB  - Although the role of memory in visual search is debatable, most researchers agree
      with a limited-capacity model of memory in visual search. The authors demonstrate
      the role of memory by replicating previous findings showing that visual search is
      biased away from old items (previously examined items) and toward new items
      (nonexamined items). Furthermore, the authors examined the type of memory
      representations used to bias search by changing an item's individuating feature
      or location during search. Changing the individuating feature of an item did not
      disrupt normal search biases. However, when the location of an item changed,
      normal search biases were disrupted. These results suggest that memory used in
      visual search is based on items' locations rather than their identity.

PMID- 16634669
TI  - Tau as a potential control variable for visually guided braking.
AB  - D. N. Lee (1976) described a braking strategy based on optical expansion in which
      the driver brakes so that the target's time-to-contact declines around a constant
      slope in the range -0.5 < or = tau < 0. The present results from a series of
      braking simulations confirm and extend earlier reports (E. H. Yilmaz & W. H.
      Warren, 1995) that performance is broadly compatible with the tau hypothesis.
      However, performance was not enhanced in situations that favored the estimation
      of tau, and unlike in earlier reports, performance deteriorated in the absence of
      a ground plane that provided information about speed and target distance. This
      finding suggests that the tau hypothesis does not provide a complete account of
      braking control.

PMID- 16634670
TI  - Simon effect with and without awareness of the accessory stimulus.
AB  - The authors investigated whether a Simon effect could be observed in an accessory
      stimulus Simon task when participants were unaware of the task-irrelevant
      accessory cue. In Experiment 1A a central visual target was accompanied by a
      suprathreshold visual lateral cue. A regular Simon effect (i.e., faster cue
      response corresponding reaction times [RTs]) was found. Experiment 1B
      demonstrated that this effect cannot be attributed to perceptual grouping of the
      target and cue. Experiments 2A, 2B, and 2C showed a reverse Simon effect (i.e.,
      faster noncorresponding RTs) when participants were not aware of the cue. In this
      condition, the Simon effect would occur relative to the reorientation of
      attention from the cue, which would initially capture attention, toward the
      target. This conclusion is supported by the results of Experiments 3A and 3B, in
      which the reorientation of attention was induced by having the target flash after
      its onset. With suprathreshold cues either a reverse or regular Simon effect was
      observed by using a 100-ms or > or = 200-ms onset flashing interval,
      respectively, whereas with subthreshold cues a reverse Simon effect was found
      irrespective of the interval length.

PMID- 16634671
TI  - Sequence learning and selection difficulty.
AB  - The authors studied the role of attention as a selection mechanism in implicit
      learning by examining the effect on primary sequence learning of performing a
      demanding target-selection task. Participants were trained on probabilistic
      sequences in a novel version of the serial reaction time (SRT) task, with dual-
      and triple-stimulus participants having to ignore irrelevant items in the SRT
      display. Despite large performance decrements under dual- and triple-stimulus
      configurations, testing under single-stimulus conditions revealed no impairment
      to sequence learning. These findings suggest that implicit sequence learning is
      resistant to disruption of the selection process. Results are discussed in terms
      of a componential model of attention and in relation to the implicit-explicit
      distinction.

PMID- 16634672
TI  - Learning to control collisions: the role of perceptual attunement and action
      boundaries.
AB  - The authors investigated the role of perceptual attunement in an emergency
      braking task in which participants waited until the last possible moment to slam
      on the brakes. Effects of the size of the approached object and initial speed on
      the initiation of braking were used to identify the optical variables on which
      participants relied at various stages of practice. In Experiments 1A and 1B, size
      and speed effects that were present early in practice diminished but were not
      eliminated as participants learned to initiate braking at a rate of optical
      expansion that varied with optical angle. When size and speed were manipulated
      together in Experiment 2, the size effect was quickly eliminated, and
      participants learned to use a 3rd optical variable (global optic flow rate) to
      nearly eliminate the speed effect. The authors conclude that perceptual
      attunement depends on the range of practice conditions, the availability of
      information, and the criteria for success.

PMID- 16634673
TI  - Speeded old-new recognition of multidimensional perceptual stimuli: modeling
      performance at the individual-participant and individual-item levels.
AB  - Observers made speeded old-new recognition judgments of color stimuli embedded in
      a multidimensional similarity space. The paradigm used multiple lists but with
      the underlying similarity structures repeated across lists, to allow for
      quantitative modeling of the data at the individual-participant and individual
      item levels. Correct-rejection response times (RTs) got systematically faster as
      the similarity of foils to the old study items decreased. There were also
      intricate patterns of speed-accuracy trade-offs that varied across individual
      items and participants. An exemplar-based random-walk model provided a good
      overall quantitative account of the recognition choice probabilities, mean
      correct RTs, and mean error RTs associated with the individual items on the basis
      of their positions in multidimensional similarity space. However, the model
      failed to predict the very long RTs associated with correct rejections of a
      prototype foil.

PMID- 16634674
TI  - Eye movements and lexical ambiguity resolution: investigating the subordinate
      bias effect.
AB  - Recent debates on lexical ambiguity resolution have centered on the subordinate
      bias effect, in which reading time is longer on a biased ambiguous word in a
      subordinate-biasing context than on a control word. The nature of the control
      word--namely, whether it matched the frequency of the ambiguous word's overall
      word form or its contextually instantiated word meaning (a higher or lower
      frequency word, respectively)--was examined. In addition, contexts that were
      singularly supportive of the ambiguous word's subordinate meaning were used. Eye
      movements were recorded as participants read contextually biasing passages that
      contained an ambiguous word target or a word-form or word-meaning control. A
      comparison of fixation times on the 2 control words revealed a significant effect
      of word frequency. Fixation times on the ambiguous word generally fell between
      those on the 2 controls and were significantly different than both. Results are
      discussed in relation to the reordered access model, in which both meaning
      frequency and prior context affect access procedures.

PMID- 16634675
TI  - The attentional white bear phenomenon: the mandatory allocation of attention to
      expected distractor locations.
AB  - The authors devised a prestimulus-probe method to assess the allocation of
      attention as a function of participants' top-down expectancies concerning
      distractor and target locations. Participants performed the flanker task, and
      distractor locations remained fixed. On some trials, instead of the flanker
      display, either 2 simultaneous dots or a horizontal line appeared. The dot in the
      expected distractor location was perceived to occur before the dot in the
      expected empty location, and the line appeared to extend from the expected
      distractor location to the expected empty location, suggesting that attention is
      allocated to expected distractor locations prior to stimulus onset. The authors
      propose that a process-all mechanism guides attention to expected locations of
      all stimuli regardless of task demands and that this constitutes a major cause
      for failures of selective attention.

PMID- 16634676
TI  - The beneficial effects of additional task load, positive affect, and instruction
      on the attentional blink.
AB  - The attentional blink reflects the impaired ability to identify the 2nd of 2
      targets presented in close succession--a phenomenon that is generally thought to
      reflect a fundamental cognitive limitation. However, the fundamental nature of
      this impairment has recently been called into question by the counterintuitive
      finding that task-irrelevant mental activity improves attentional blink
      performance (C. N. L. Olivers & S. Nieuwenhuis, 2005). The present study found a
      reduced attentional blink when participants concurrently performed an additional
      memory task, viewed pictures of positive affective content, or were instructed to
      focus less on the task. These findings support the hypothesis that the
      attentional blink is due to an overinvestment of attentional resources in
      stimulus processing, a suboptimal processing mode that can be counteracted by
      manipulations promoting divided attention.

PMID- 16634677
TI  - Qualitative and quantitative change in the dynamics of motor learning.
AB  - The experiments examined qualitative and quantitative changes in the dynamics of
      learning a novel motor skill (roller ball task) as a function of the manipulation
      of a control parameter (initial ball speed). The focus was on the relation
      between the rates of change in performance over practice time and the changing
      time scales of the evolving attractor dynamic. Results showed 3 different
      learning patterns to the changes in the dynamics as a function of practice that
      were mediated by the initial ball speed. Only participants who learned the task
      showed a bifurcation in coordination mode that was preceded by enhanced
      performance variability. The observed multiple time scales to motor learning are
      interpreted as the products of the dynamical stability and instability realized
      from (a) the continually evolving landscape dynamics due to bifurcations between
      attractor organization and (b) the transient phenomena associated with moving
      toward and away from fixed-point dynamics.

PMID- 16634678
TI  - Dissociations between reaction times and temporal order judgments: a diffusion
      model approach.
AB  - A diffusion model for simple reaction time (RT) and temporal order judgment (TOJ)
      tasks was developed to account for a commonly observed dissociation between these
      2 tasks: Most stimulus manipulations (e.g., intensity) have larger effects in RT
      tasks than in TOJ tasks. The model assumes that a detection criterion determines
      the level of sensory evidence needed to conclude that a stimulus has been
      presented. Analysis of the performance that would be achieved with different
      possible criterion settings revealed that performance was optimal with a lower
      criterion setting for the TOJ task than for the RT task. In addition, the model
      predicts that effects of stimulus manipulations should increase with the size of
      the detection criterion. Thus, the model suggests that commonly observed
      dissociations between RT and TOJ tasks may simply be due to performance
      optimization in the face of conflicting task demands.

PMID- 16634679
TI  - The effect of the Muller-Lyer illusion on the planning and control of manual
      aiming movements.
AB  - Two experiments used Muller-Lyer stimuli to test the predictions of the planning
      control model (S. Glover, 2002) for aiming movements. In Experiment 1,
      participants aimed to stimuli that either remained the same or changed upon
      movement initiation. Experiment 2 was identical except that the duration of
      visual feedback for online control was manipulated. The authors found that the
      figures visible during movement planning and online control had additive effects
      on endpoint bias, even when participants had ample time to use visual feedback to
      modify their movements (Experiment 2). These findings are problematic not only
      for the planning-control model but also for A. D. Milner and M. A. Goodale's
      (1995) two visual system explanation of illusory bias. Although our results are
      consistent with the idea that a single representation is used for perception,
      movement planning, and online control (e.g., V. H. Franz, 2001), other work from
      our laboratory and elsewhere suggests that the manner in which space is coded
      depends on constraints associated with the specific task, such as the visual cues
      available to the performer.

PMID- 16634680
TI  - The effect of items in working memory on the deployment of attention and the eyes
      during visual search.
AB  - Paying attention to an object facilitates its storage in working memory. The
      authors investigate whether the opposite is also true: whether items in working
      memory influence the deployment of attention. Participants performed a search for
      a prespecified target while they held another item in working memory. In some
      trials this memory item was present in the search display as a distractor. Such a
      distractor has no effect on search time if the search target is in the display.
      In that case, the item in working memory is unlikely to be selected as a target
      for an eye movement, and if the eyes do land on it, fixation duration is short.
      In the absence of the target, however, there is a small but significant effect of
      the memory item on search time. The authors conclude that the target for visual
      search has a special status in working memory that allows it to guide attention.
      Guidance of attention by other items in working memory is much weaker and can be
      observed only if the search target is not present in the display.

PMID- 16634681
TI  - Lateral interception I: operative optical variables, attunement, and calibration.
AB  - J. J. Gibson (1966, 1979) suggested that improvement in perception and action can
      be attributed in part to changes in which variable is attended to. Such
      reattunement has been demonstrated with observers making judgments in response to
      simulations. The present study sought attunement changes in the perception of
      real events and in visually guided action. In 3 experiments, adults judged the
      passing distance of or attempted to catch balls. Discrete measures and the
      predictions of a modified required velocity model (e.g., R. J. Bootsma, V. Fayt,
      F. T. J. M. Zaal, & M. Laurent, 1997) were used to reveal which variables were
      exploited. Participants differed from each other and, to some extent, changed in
      the optical variables used, in catching as well as judging. Nevertheless, the
      changes were much smaller than in previous simulation-judgment studies;
      calibration was also found to underlie the improvements in performance.

PMID- 16634682
TI  - Lateral interception II: predicting hand movements.
AB  - D. M. Jacobs and C. F. Michaels (2006) concluded that aspects of hand movements
      in lateral catching were predicted by the ratio of lateral optical velocity to
      expansion velocity. Their conclusions were based partly on a modified version of
      the required velocity model of catching (C. E. Peper, R. J. Bootsma, D. R.
      Mestre, & F. C. Bakker, 1994). The present article considers this optical ratio
      in detail and asks whether it, together with a control law, predicts the (often
      curious) hand trajectories observed in lateral interception. The optical ratio
      was used to create a succession of target-position inputs for the vector
      integration to endpoint model of hand movements (D. Bullock & S. Grossberg,
      1988). The model used this succession, initial hand position, and model
      parameters (fit to 60 trials) to predict hand trajectories on each trial.
      Predicted trajectories were then compared with observed hand trajectories. Hand
      movements were predicted accurately, especially in the binocular condition, and
      were superior to predictions based on lateral ball position, the input variable
      of the required velocity model. The authors concluded, as did C. E. Peper et al.
      (1994), that perceivers continuously couple movements to optics.

PMID- 16634683
TI  - Toward a formal theory of flexible spatial behavior: geometric category biases
      generalize across pointing and verbal response types.
AB  - Three experiments tested whether geometric biases--biases away from perceived
      reference axes--reported in spatial recall tasks with pointing responses
      generalized to a recognition task that required a verbal response. Seven-year
      olds and adults remembered the location of a dot within a rectangle and then
      either reproduced its location or verbally selected a matching choice dot from a
      set of colored options. Results demonstrated that geometric biases generalized to
      verbal responses; however, the spatial span of the choice set influenced
      performance as well. These data suggest that the same spatial memory process
      gives rise to both response types in this task. Simulations of a dynamic field
      model buttress this claim. More generally, these results challenge accounts that
      posit separate spatial systems for motor and verbal responses.

PMID- 16634684
TI  - Oral CCR5 inhibitors: will they make it through?
AB  - The therapeutic armamentarium against HIV has recently gained a drug belonging to
      a novel class of antiretrovirals, the entry inhibitors. The last decade has
      driven an in-depth knowledge of the HIV entry process, unravelling the multiple
      engagements of the HIV envelope proteins with the cellular receptorial complex
      that is composed of a primary receptor (CD4) and a co-receptor (CCR5 or CXCR4).
      The vast majority of HIV-infected subjects exhibit biological viral variants that
      use CCR5 as a co-receptor. Individuals with a mutated CCR5 gene, both homo- and
      heterozygotes, appear to be healthy. For these and other reasons, CCR5 represents
      an appealing target for treatment intervention, although certain challenges can
      not be ignored. Promising small-molecule, orally bioavailable CCR5 antagonists
      are under development for the treatment of HIV-1 infection.

PMID- 16634685
TI  - Progress in identifying peptides and small-molecule inhibitors targeted to gp41
      of HIV-1.
AB  - During the last decade, a great number of activities have been geared in
      identifying newer targets for inhibiting HIV infection as well as understanding
      the targets for already identified anti-HIV-1 agents. The success in converting a
      proof-of-concept peptide T-20 (previously named DP-178), from the C-terminal
      heptad repeat (CHR) region of the envelope glycoprotein gp41 of HIV-1, to a drug
      named enfuvirtide was one of the phenomenal successes in HIV-1 drug discovery
      research that has been made in recent years. There were many reports of modifying
      peptides from the N-terminal heptad repeat and CHR regions with the objective of
      improving their activity. A few laboratories also reported the identification of
      small-molecule inhibitors that apparently bind to the hydrophobic cavity
      identified in the gp41 core structure and prevent the CHR peptide binding to the
      N-terminal heptad repeat peptide, thereby prevent the formation of the typical
      six-helix bundle, which has been thought to be necessary for the fusion between
      HIV and cell membranes.

PMID- 16634686
TI  - NK1 receptor antagonists under investigation for the treatment of affective
      disorders.
AB  - Substance P-neurokinin-1 (NK1) receptor pathways have been repeatedly implicated
      in the pathophysiology of affective disorders. Anatomical studies in humans have
      shown a high expression of NK1 receptors in brain regions that are important for
      the regulation of affective behaviours and stress responses. A large body of
      evidence that has been generated from animal experiments indicates that treatment
      with a selective NK1 receptor antagonist might be effective in the treatment of
      certain forms of anxiety and depressive disorders. Accordingly, numerous NK1
      receptor antagonists have either been synthesised and are under clinical
      development, or have already been tested in clinical trials. However, the initial
      encouraging clinical results were followed by repeated demonstrations of a lack
      of effectiveness, thus disappointment and doubt currently surrounds the idea that
      these compounds may become effective antidepressants. Research continues and
      novel molecules may show better pharmacokinetic and pharmacodynamic properties
      and, therefore, may achieve therapeutic success. Furthermore, NK1 receptor
      antagonists that are ineffective in the treatment of mood disorders may still
      prove to be effective in the treatment of anxiety problems.

PMID- 16634687
TI  - Treatment of early heart failure: an ACEI or a beta-blocker first?
AB  - The basis of modern chronic heart failure (CHF) treatment is a combination of
      optimum doses of a beta-blocker and an angiotensin-converting enzyme inhibitor
      (ACEI); however, patients cannot be started on full doses of both drugs and
      treatment has to be initiated one way or the other. By tradition and according to
      guideline recommendations, an ACEI is usually initiated first, followed by a beta
      blocker after a varying time period based on clinical judgement. Early beta
      blockade has several theoretical advantages, and two surrogate end point studies
      have indicated that initiation of CHF treatment with a beta-blocker may be
      superior to an ACEI. The Cardiac Insufficiency Bisoprolol III trial was the first
      trial investigating the optimum sequence of initiating treatment of CHF in terms
      of mortality and morbidity. The results indicated that, in stable, mildly to
      moderately symptomatic patients with systolic CHF, initiation of therapy with the
      beta-blocker bisoprolol followed by the ACEI enalapril was similarly efficacious
      to the opposite sequence in terms of combined mortality and all-cause
      hospitalisation. However, initiating therapy with bisoprolol showed a trend
      towards better survival, but also towards further worsening of CHF. This review
      aims to put these recent findings into clinical perspective.

PMID- 16634688
TI  - Treatment of central precocious puberty.
AB  - The problems of central precocious puberty (CPP) are serious enough to the
      patient to deserve treatment. There is a general consensus among paediatric
      endocrinologists that the treatment of true CPP (i.e., in children young enough
      to have a formal diagnosis) is indicated in many cases. In children with modestly
      early puberty who are not fulfilling the diagnostic criteria, this is not the
      case. The treatment of choice is a gonadotropin-releasing hormone (GnRH)
      analogue. Prolonged analogues are more effective than short-acting ones and, most
      importantly, independent of patient compliance. Data on agonists have accumulated
      over two decades and evidence of effects is rich in girls but sparse in boys.
      GnRH agonists are generally effective and safe drugs; the suppression of puberty
      is reversible and there is much information on GnRH agonists for the treatment of
      CPP showing very few adverse effects and the effects on final height are well
      documented in girls < 6 years of age. There is some (but not highly convincing)
      evidence for their effect on final height for those of 6 - 8 years of age and
      there is no evidence for an increase in final height after the age of 8 years in
      girls. If a decision to have treatment is taken, treatment should start
      immediately as a possible benefit is less probable if the start of treatment is
      delayed. When treatment should be stopped is a matter of controversy. Combination
      with growth hormone increases final height, but the clinical relevance can be
      discussed as well as the health economy aspects. The limits of indications are
      still to be defined.

PMID- 16634689
TI  - The potential of clusterin inhibiting antisense oligodeoxynucleotide therapy for
      prostate cancer.
AB  - This review summarise the authors' recent experience in the development of
      antisense (AS) oligodeoxynucleotide (ODN) therapy that targets a cytoprotective
      gene, clusterin, for the treatment of prostate cancer. The acquisition of
      resistance to a wide variety of proapototic stimuli was initially demonstrated by
      introducing the clusterin gene into prostate cancer cells. Furthermore, silencing
      clusterin expression using AS ODN synergistically enhanced the effects of several
      conventional therapeutic modalities through the effective induction of apoptosis
      in prostate cancer xenograft models. Based on these outcomes, Phase I clinical
      trials were conducted using AS clusterin ODN incorporating 2'-O-(2-methoxy)ethyl
      gapmer backbone (OGX-011), and the optimal dose of OGX-011 capable of inducing
      </= 90% suppression of clusterin in human prostate cancer tissue was determined.
      Collectively, these findings suggest the utility of inactivating clusterin
      function using AS ODN technology as a novel therapeutic strategy for prostate
      cancer treatment. There have been four kinds of Phase II studies that have begun
      to further evaluate the efficacy of OGX-011 in patients with prostate, breast and
      lung cancers.

PMID- 16634690
TI  - The treatment of urinary tract infections and use of ciprofloxacin extended
      release.
AB  - Urinary tract infections (UTIs) are one of the most common reasons people seek
      medical attention. There are > 50% of women who will have at least one UTI during
      their lifetime and most of these will require a physician visit and antibiotic
      treatment. The high prevalence continues to the in-patient setting where
      genitourinary infections are the most common nosocomial infection. The efficient
      diagnosis and effective treatment of UTIs is a major healthcare concern. Factors
      such as economic efficiency and emerging resistance are increasingly becoming
      more important considerations in providing patient care. In out-patient
      uncomplicated UTIs, Escherichia coli has been implicated in < or = 75-90% of
      cases. Although the prevalence in the in-patient setting decreases, E. coli is
      still the most common bacteria identified and present in 21-54% of urinary
      isolates. Trimethoprim-sulfamethoxazole has been the preferred first-line agent
      for uncomplicated out-patient UTIs where local resistance is < 10 - 20%. In
      recent years, resistance has superseded this threshold in most regions of the US
      and Europe. In these areas with increased resistance, fluoroquinolones have
      become a common first-line agent. Ciprofloxacin has been one of the most widely
      used fluoroquinolones and has a well-known safety profile, as well as excellent
      activity against most of the common uropathogens. Ciprofloxacin extended release
      (ER) is a recently released once-daily formulation that has been increasingly
      used with good clinical success. The pharmacokinetic and pharmacodynamic
      parameters of ciprofloxacin ER are shown to be at least equal to twice-daily
      ciprofloxacin and may even confer superiority as ciprofloxacin ER achieves a
      higher maximum serum concentration. This is supported by clinical studies, which
      have shown at least as effective clinical cure and bacteriological eradication
      rates. These studies have also demonstrated similar tolerability and side-effect
      profiles. Ciprofloxacin ER combines traditional ciprofloxacin's proven track
      record of efficacy and safety with favourable pharmacokinetics and convenient
      once-daily dosing. Increased patient compliance is associated with decreased
      treatment failures and can help slow the development of antimicrobial resistance.
      Economic considerations are also increasingly important and providing convenient
      and effective treatment leading to high clinical success decreases overall costs.

PMID- 16634691
TI  - Tolvaptan: a selective vasopressin type 2 receptor antagonist in congestive heart
      failure.
AB  - The neurohormone arginine vasopressin plays a significant role in the regulation
      of volume homeostasis, which is mediated via vasopressin type 2 (V2) receptors in
      the collecting tubules of the kidney. Diseases that are accompanied by abnormal
      volume homeostasis, including congestive heart failure and cirrhosis, are a
      frequent cause of hospital admissions and increasing healthcare costs. Recently,
      several nonpeptide V2 receptor antagonists have emerged as promising agents in
      the management of these conditions with the advantage of having no electrolyte
      abnormalities, neurohormonal activation or worsening renal insufficiency.
      Tolvaptan, a highly selective nonpeptide V2 receptor antagonist, has demonstrated
      an improvement in the volume status, osmotic balance and haemodynamic profile in
      preclinical and Phase II trials in patients with congestive heart failure and is
      currently undergoing testing in Phase III trials. This review discusses the
      evidence for the potential uses of tolvaptan, and its pharmacology and
      pharmacokinetics, particularly in congestive heart failure.

PMID- 16634692
TI  - Methylnaltrexone, a novel peripheral opioid receptor antagonist for the treatment
      of opioid side effects.
AB  - Methylnaltrexone is an investigational peripheral opioid receptor antagonist, a
      quaternary derivative of naltrexone. Methylnaltrexone has greater polarity and
      lower lipid solubility, thus it does not cross the blood-brain barrier in humans.
      Methylnaltrexone offers the therapeutic potential to block or reverse the
      undesired side effects of opioids that are mediated by receptors located in the
      periphery (e.g., in the gastrointestinal tract), without affecting analgesia or
      precipitating the opioid withdrawal symptoms that are predominantly mediated by
      receptors in the CNS. This article reviews preclinical studies and clinical
      opioid bowel dysfunction trial data, and briefly discusses other potential roles
      of this compound in clinical practice.

PMID- 16634693
TI  - Sunitinib malate for the treatment of solid tumours: a review of current clinical
      data.
AB  - Receptor tyrosine kinases (RTKs) play important roles in the regulation of
      cellular growth, and mutated or overexpressed RTKs have been implicated in
      various human cancers. Sunitinib malate is an oral multitargeted tyrosine kinase
      inhibitor with antitumour and antiangiogenic activity that recently received
      approval from the FDA for the treatment of advanced renal cell carcinoma and of
      gastrointestinal stromal tumours after disease progression on or intolerance to
      imatinib mesilate therapy. Sunitinib has also demonstrated promising clinical
      activity in the treatment of other advanced solid tumours. The present review
      provides an updated summary of emerging clinical experience with this promising
      new anticancer agent.

PMID- 16634694
TI  - Annual meeting of the American Heart Association. Dallas, Texas, USA, 13-16
      November 2005.

PMID- 16634696
TI  - Is there a need for a new generation of vaccines against pertussis?
AB  - Current vaccines against pertussis have proved their safety and efficacy in large
      scale clinical trials. Despite high vaccination coverage, pertussis is still
      prevalent and increasing, probably as a result of waning immunity. Addition of
      new antigens, such as adenylate cyclase, to current vaccines might improve some
      aspects of the immune response to vaccination, but are unlikely to significantly
      increase the duration of protection. Intranasal, oral and DNA pertussis vaccines
      are some way from clinical development, although one live attenuated, intranasal
      pertussis vaccine may soon enter Phase I trials. In the meantime, the potential
      of currently available safe and efficacious pertussis vaccines should be
      maximised. Rationalisation of pertussis boosters in childhood and introduction of
      widespread repeat booster vaccination in adolescents and adults would already
      lessen disease prevalence and morbidity among susceptible infants.

PMID- 16634697
TI  - Tuberculosis vaccines: current status and future prospects.
AB  - There is an urgent need to develop more effective tuberculosis vaccines as
      chemotherapy and Bacille Calmette-Guerin (BCG) have failed to control the current
      epidemic. BCG does have some protective effect in childhood, so using a second
      vaccine to boost BCG would be the most ethical and logistically feasible
      strategy. The cost of tuberculosis efficacy trials will be high and return on
      investment into the development of a tuberculosis vaccine will be low. Incentives
      such as orphan drug status could encourage industrial interest. As more vaccines
      enter into early clinical trials, there is an urgent need for the identification
      of correlates of protection to aid decisions about which vaccines should go
      forward into efficacy testing. Research efforts that focus on reducing the cost
      and risk of conducting clinical trials will be of direct benefit to tuberculosis
      vaccine development.

PMID- 16634698
TI  - Emerging reverse transcriptase inhibitors for the treatment of HIV infection in
      adults.
AB  - A combination of three or more antiretroviral drugs, commonly called 'highly
      active antiretroviral therapy' (HAART), has become the standard-of-care treatment
      for HIV-infected patients in the developed world. There are now 21 licensed anti
      HIV drugs to choose from when starting a HAART regimen. The currently approved
      antiretroviral drugs fall into four categories: nucleoside/nucleotide reverse
      transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors,
      protease inhibitors and fusion inhibitors. Novel compounds currently in
      preclinical or clinical development are either focusing on new viral proteins or
      the same specific viral elements targeted by the available drugs. When developing
      new anti-HIV drugs of an already existing class, focus should be held on
      maximising potency, minimising toxicity, diminishing the risk for resistance
      development and producing effective drugs for patients who already have
      resistance to currently available drugs. In addition, pill burden should be
      ideally reduced to once-daily dosing, thereby enhancing a patient's adherence and
      reducing treatment costs. The present review focuses on emerging drugs to inhibit
      the reverse transcriptase of HIV.

PMID- 16634699
TI  - Emerging echinocandins for treatment of invasive fungal infections.
AB  - The echinocandins are a new class of antifungals, developed in response to the
      need for safe and effective antifungals for the treatment of invasive fungal
      infections. These agents work by inhibiting 1,3-beta-d-glucan synthase, an enzyme
      essential for production of cell walls in select fungi. Echinocandins appear to
      demonstrate favourable activity in vitro against a variety of yeasts (including
      both Candida albicans and non-albicans Candida) as well as select moulds
      (including Aspergillus spp.) In general, all echninocandins demonstrate a
      favourable safety profile and require once-daily parenteral administration.
      Caspofungin is the first of these agents to be available in the US, and is
      approved for empirical antifungal therapy in febrile neutropenic patients,
      candidaemia and select forms of invasive candidiasis, and for management of
      invasive aspergillosis in patients refractory to or intolerant of other
      therapies. Micafungin was recently approved by the FDA for treatment of
      oesophageal candidiasis, and for the prophylaxis of fungal infections in
      haematopoietic stem cell transplant recipients. Emerging data indicate micafungin
      may have an important role in the treatment of invasive forms of candidiasis.
      Anidulafungin is an echinocandin approved in the US for treatment of candidaemia
      and oesophageal candidiasis. Aminocandin (HMR-3702, IP-960) is an investigational
      agent, with published experience limited to in vitro studies and animal models of
      infection.

PMID- 16634700
TI  - Emerging therapies for the treatment and prevention of otitis media.
AB  - Otitis media is one of the most common disorders occurring in children, and there
      is growing concern that bacteria are quickly becoming resistant to
      antimicrobials. As a result, global antibiotic treatment is no longer the
      standard of care and treatment of otitis media has changed dramatically in the
      last decade. In addition to new antimicrobials currently in development, the
      effects of the pneumococcal conjugate vaccine are just beginning to be
      understood. Furthermore, new surgical techniques are for the first time being
      tested as alternatives for tympanostomy tubes for recurrent acute otitis media.
      This review discusses current and emerging otitis media therapeutics, with
      particular attention to acute otitis media. Topics include antimicrobial use,
      antimicrobial resistance, effects of vaccination and new surgical techniques.

PMID- 16634701
TI  - Emerging drugs for chronic urticaria.
AB  - Chronic urticaria (CU), with or without angioedema, is a frequent disorder
      defined as the occurrence of pruritic wheals for > 6 weeks. Studies carried out
      in the last two decades showed that the origin of the disease is autoimmune in up
      to 50% of cases. Currently available treatments include antihistamines,
      corticosteroids and ciclosporin; recently, leukotriene receptor antagonists
      proved effective in a subset of patients as well. For patients with an
      unremitting and extremely severe disease unresponsive to standard treatments,
      plasmapheresis and immunosuppressive drugs have been successfully attempted.
      Recent findings that the autologous plasma skin test scores positive in nearly
      all patients and that plasmas from patients with both autoimmune and 'idiopathic'
      chronic urticaria are frequently characterised by signs of thrombin activation
      (plasma levels of prothrombin fragment F(1.2) are significantly increased)
      suggest that clotting cascade might be somehow involved in the pathogenesis of
      CU. These findings put under a new light some rather sparse studies of the effect
      of drugs active on the coagulation system (heparin and oral anticoagulants) in
      patients with CU.

PMID- 16634702
TI  - Emerging drugs for the treatment of chronic obstructive pulmonary disease.
AB  - By 2020 chronic obstructive pulmonary disease (COPD) will be the third leading
      cause of mortality and fifth leading cause of morbidity. Research over the past
      two decades has shed important insights on the pathobiology of COPD, leading to
      the development of novel drugs. In the past, symptomatic treatment with
      bronchodilators was the predominant focus of COPD management. With increased
      awareness of the importance of airway inflammation in COPD progression, there has
      been a shift in emphasis to drugs that attack various targets in the inflammatory
      cascade. These drugs include phosphodiesterase 4 inhibitors, leukotriene
      modifiers and TNF antagonists, which are poised to enter the COPD market in the
      very near future. Tyrosine kinase antagonists, inhibitors of NF-kappaB,
      neutrophil elastase inhibitors, chemokine antagonists, mucolytics and novel
      antibiotics are being evaluated for possible effectiveness in COPD. Many of these
      drugs may enter the COPD market within the next decade. This paper reviews the
      molecular rationale for these emerging drugs and their potential efficacy in
      COPD.

PMID- 16634703
TI  - Emerging drugs for irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is one of the most common chronic gastrointestinal
      disorders, yet its pathophysiology is incompletely understood and pharmacological
      treatments remain unsatisfactory. Current therapeutic choices include a range of
      drugs aimed at normalising bowel habits, reducing pain or treating comorbid
      psychological symptoms. However, this individual symptom-targeted approach
      remains unsatisfactory in terms of global symptom relief and patient
      satisfaction. In the last decade, further characterisation of IBS pathophysiology
      has provided new and exciting targets at different levels of the brain-gut axis
      for the development of several candidate drugs. Advances in clinical trial design
      will help to evaluate these compounds in different IBS patient populations.

PMID- 16634704
TI  - Emerging drugs for eating disorder treatment.
AB  - Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED)
      comprise the currently recognised eating disorders. Although distinct diagnostic
      entities, they share certain forms of comorbid psychopathology, particularly
      anxiety and mood disorders. BN and BED have been studied most intensively as
      targets for pharmacotherapy. The list of drugs tested in eating disorders is
      substantial; however, the number of therapeutic classes of medications tested in
      these conditions is relatively modest. Antidepressant medications, including
      tricyclic antidepressants, selective serotonin re-uptake inhibitors, as well as
      some of the novel antidepressants, have shown evidence of some therapeutic value
      in both BN and BED. Their efficacy in AN, however, has been disappointing. The
      pharmacological options for AN are very limited. The number of controlled trials
      that have been conducted is small, and the research that has been successfully
      completed has generally failed to demonstrate medication efficacy. Patients with
      BN typically show reduced binge eating and purging frequency in medication
      trials, but rarely attain abstinence. In BED, patients often measure the value of
      their medication therapy by its ability to stimulate weight loss, which is
      another area on which future pharmacotherapy may improve. Novel pharmacological
      interventions are needed for each of these conditions. Peptide hormones are
      increasingly being evaluated for eating disorder treatment, including ghrelin
      agonists, neuropeptide Y1 and -5 antagonists, orexin receptor antagonists,
      corticotropin-releasing factor receptor 2 antagonists, histamine 3 antagonists,
      melanocortin 4 receptor antagonists, beta3-adrenoceptor agonists, 5
      hydroxytryptamine-2A antagonists and growth hormone agonists. Although these
      compounds are in early phases of clinical testing for eating disorder treatments,
      data from these studies will be instructive in the quest for effective
      pharmacotherapy for these conditions. An overview of the current pharmacotherapy
      options for eating disorders is presented with a discussion of the emerging
      potential treatments.

PMID- 16634705
TI  - Antisense-based cancer therapeutics: are we there yet?
AB  - Despite significant advances that have been made in recent years, there is still
      an urgent need for novel, more effective and less toxic therapeutics for human
      cancer. Among many new molecular therapeutics being explored for cancer therapy,
      antisense oligonucleotides are a promising nucleic acid-based approach, with
      numerous antisense agents being evaluated in preclinical studies and several
      anticancer antisense drugs in clinical trials. Although there are still a few
      problems facing the development of antisense strategies for cancer therapy, with
      progress made in chemical modifications, target selection and drug delivery
      systems, antisense oligonucleotides are emerging as a novel approach to cancer
      therapy used alone or in combination with conventional treatments such as
      chemotherapy and radiation therapy.

PMID- 16634706
TI  - Emerging approaches for prophylaxis and management of oropharyngeal mucositis in
      cancer therapy.
AB  - Oral mucositis is a common treatment-limiting side effect of cancer therapy that
      may have a significant impact on quality of life and on the cost of care. Oral
      mucositis is the most distressing complication of cancer therapy as reported by
      head and neck cancer patients, in patients receiving dose-dense myelosuppressive
      chemotherapy and in patients receiving haematopoietic stem cell transplant.
      Mucositis may increase the risk of local and systemic infection, particularly in
      myelosuppressed patients. Severe oral mucositis can lead to the need to interrupt
      or discontinue cancer therapy, and thus may impact cure of the primary disease.
      Current care of patients with mucositis is essentially palliative, and includes
      appropriate oral hygiene, nonirritating diet and oral care products, topical
      palliative mouth rinses, topical anaesthetics and use of systemic opioid
      analgesics. Emerging approaches for prevention and treatment of oral mucositis
      are developing based on an increasing understanding of the pathobiology of
      mucosal damage and repair. New interventions are expected to be administered
      based on the mechanisms of initiation, progression and resolution of the
      condition. The approval by the FDA of keratinocyte growth factor (palifermin;
      Amgen) in 2004 represents a new step in prevention of oral mucositis in stem cell
      transplant patients based on the increasing understanding of the pathogenesis of
      mucositis. Progress in the prevention and management of mucositis will improve
      quality of life, reduce cost of care and facilitate completion of more intensive
      cancer chemotherapy and radiotherapy protocols. Improved management of mucositis
      may allow implementation of cancer treatment protocols that are currently
      excessively mucotoxic, but have potentially higher cure rates of the malignant
      disease.

PMID- 16634707
TI  - Neuroprotective agents in schizophrenia and affective disorders.
AB  - With the exception of dementia, the use of neuroprotective agents in psychiatric
      disorders is not yet well established. However, recent data from brain imaging
      studies and clinical trials support the view that neurodegenerative mechanisms
      may play a role in the pathophysiology of schizophrenia and affective disorders.
      Further evidence for the use of neuroprotective agents can be drawn from the
      findings that second-generation antipsychotics, mood stabilizers and
      antidepressants have been shown to have neuroprotective effects in vitro and in
      vivo. Neuroprotective agents as add-on therapies (e.g., modafinil,
      erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being
      evaluated in schizophrenia and related disorders. This paper reviews the current
      options for neuroprotective treatment approaches focusing on schizophrenia and
      affective disorders.

PMID- 16634708
TI  - Polymorphisms in candidate genes: implications for the current treatment of
      Parkinson's disease.
AB  - Pharmacological treatment remains the cornerstone of therapy in Parkinson's
      disease. A number of clinical and genetic factors may influence the therapeutic
      response and treatment-related complications. Some exploratory studies have
      suggested that genetic polymorphisms may influence an individual's response to
      dopaminergic therapy and susceptibility to drug-related complications, such as
      hallucinations, dyskinesias, motor fluctuations and sudden onset of sleep
      episodes. This article provides a concise summary and discussion of the potential
      utility and limitation of studies that have examined the influence of genetic
      polymorphisms on drug-related response and complications in Parkinson's disease.

PMID- 16634709
TI  - Sex hormones: a role in the control of multiple sclerosis?
AB  - Several lines of evidence suggest that gender affects the susceptibility and
      course of multiple sclerosis. A higher disease prevalence, as well as an overall
      better prognosis, in women than men is observed. This sex dimorphism may be
      explained by the effect of sex hormones on brain damage and repair mechanisms.
      Experimental, clinical and MRI evidence confirms a pathogenetic link between sex
      hormones and multiple sclerosis, also suggesting sex-specific effects of hormones
      in multiple sclerosis pathology and therapy. A gender-based approach to multiple
      sclerosis could provide further benefits for its treatment and management.

PMID- 16634710
TI  - Developments and current pharmacotherapeutic recommendations for ankylosing
      spondylitis.
AB  - The introduction of anti-TNFalpha therapy into the field of rheumatology has led
      to dramatic improvements in patient care, perhaps the most remarkable being in
      the management of ankylosing spondylitis. As experience with these compounds
      grows, their place in therapeutic strategy is becoming clearer, and it has been
      possible to develop evidence- and expertise-based recommendations for the
      management of ankylosing spondylitis to aid the clinician in patient care. This
      review outlines treatment advances in ankylosing spondylitis, including the use
      of anti-TNFalpha agents, and how these have been incorporated into clinical
      recommendations for daily use.

PMID- 16634711
TI  - Pharmacoeconomics of treatment with the newer anti-Gram-positive agents.
AB  - The unmet medical need of emerging resistance among Gram-positive pathogens, such
      as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci
      and penicillin-resistant Streptococcus pneumoniae, has driven industry towards
      the identification and development of novel anti-Gram-positive agents. Among the
      newer agents are improved quinolones, a lipopeptide, an oxazolidinone and novel
      glycopeptides. Scientific distinctions between these drugs, which impact on the
      placement, usage and, ultimately, the pharmacoeconomics of several of these new
      agents, may lead to further consideration despite poor initial observations of
      minimal improvement. Key differences in the characteristics of these drugs (i.e.,
      spectrum, activity, resistance emergence, efficacy, target, safety) provide a
      basis for an emerging pharmacoeconomic-based distinction between these newer anti
      Gram-positive agents.

PMID- 16634712
TI  - Chemoprevention of prostate cancer with finasteride.
AB  - Prostate cancer is a significant cause of disease and death, making it an
      attractive target for chemoprevention. The association between lifetime exposure
      to dihydrotestosterone and risk of developing prostate cancer suggests that
      chemoprevention is possible with 5alpha-reductase inhibition. The recently
      completed Prostate Cancer Prevention Trial indicates that chemoprevention is
      possible with the 5alpha-reductase inhibitor finasteride. Development of a cost
      effective chemoprevention strategy for prostate cancer is evolving, and is
      expected to have significant positive economic and public health benefits.

PMID- 16634713
TI  - Bexarotene in the treatment of cutaneous T-cell lymphoma.
AB  - Primary cutaneous T-cell lymphomas encompass a spectrum of non-Hodgkin's
      lymphomas that are characterised by clonal proliferation of skin-homing malignant
      T lymphocytes. Mycosis fungoides and the leukaemic variant Sezary syndrome,
      collectively referred to as cutaneous T-cell lymphomas, are the most common
      entities. No curative therapy exists and patients ultimately develop advanced or
      relapsed disease that is refractory to standard treatment options. Therefore,
      there is a great need for the development of novel emerging therapies. Bexarotene
      is the first synthetic nuclear retinoid X receptor-selective retinoid approved by
      the FDA for the treatment of refractory cutaneous T-cell lymphoma in all stages,
      as both an oral capsule and a topical gel formulation. Bexarotene was found to
      induce apoptosis in a variety of preclinical in vitro and in vivo models
      including cutaneous T-cell lymphoma cells, and has shown efficacy in two multi
      centre, open-label Phase II - III clinical trials for early and advanced stages
      of cutaneous T-cell lymphoma in patients who have failed or were refractory to
      standard therapies. New insights into the immunomodulatory function of bexarotene
      have indicated opportunities for combined treatment with IFN-alpha, denileukin
      diftitox or phototherapy. This article reviews the biological properties,
      pharmacokinetics, clinical efficacy, safety and role of bexarotene in the
      treatment of cutaneous T-cell lymphoma.

PMID- 16634714
TI  - Pemetrexed in thoracic cancer.
AB  - Both lung cancer and mesothelioma are malignancies with increasing incidence, and
      both are primarily due to inhalation of an external carcinogen. The occurence of
      both diseases is expected to rise worldwide, although a stabilisation and/or
      decrease may be anticipated in some developed countries. There are other common
      similarities to both cancers, including the median age of their patients, the
      advanced stage at presentation, the outcome and the treatments given. This review
      focuses on the available evidence of a novel antifolate agent, pemetrexed, in the
      treatment of both of these thoracic malignancies. Current status, persisting
      controversies and future developments are discussed.

PMID- 16634715
TI  - The role of quetiapine in the treatment of bipolar disorder.
AB  - Through a review of randomised, controlled trials, this article evaluates the
      efficacy and tolerability of quetiapine in the acute and maintenance phases of
      bipolar disorder. In trials involving mania patients, quetiapine was found to be
      effective as adjunctive therapy in combination with lithium or valproate,
      significantly superior to placebo, and equal to lithium or haloperidol as
      monotherapy. With regard to the prevention of relapses in bipolar disorder,
      quetiapine seems to differ from other atypical antipsychotics in its
      characteristics as a mood stabiliser, which are associated with a promising
      efficacy in the treatment of bipolar depressive episodes. However, further larger
      controlled long-term prospective studies are needed to confirm the efficacy of
      quetiapine for the prevention of relapses in bipolar disorder. Quetiapine seems
      to have a satisfactory safety and tolerability profile, with a low prevalence of
      extrapyramidal symptom-related adverse events, treatment-emergent depression and
      weight gain. Sedation is the main side effect of treatment with quetiapine.

PMID- 16634716
TI  - Once-daily immediate-release fexofenadine and sustained-release pseudoephedrine
      combination: a new treatment option for allergic rhinitis.
AB  - Allergic rhinitis symptoms, in particular nasal congestion, can have a
      significant impact on patient quality of life, resulting in reduced productivity
      and daytime sleepiness. Newer-generation antihistamines are commonly used to
      treat allergic rhinitis; however, in patients with severe congestion, a
      combination of a newer-generation antihistamine and a decongestant is
      particularly beneficial. A new once-daily fexofenadine/pseudoephedrine
      combination has been developed and recently approved in the US. The combination
      provides an effective, well-tolerated antihistamine and a reliable, sustained
      release pseudoephedrine system. In addition, small tablet size and once-daily
      dosing may provide patients with increased convenience and improve adherence. In
      summary, the combination of immediate-release fexofenadine/sustained-release
      pseudoephedrine offers an important additional option for the treatment of
      allergic rhinitis.

PMID- 16634717
TI  - Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment
      of gastrointestinal infections.
AB  - Colonisation of the gastrointestinal tract by anaerobic bacteria, protozoa,
      trematodes, cestodes and/or nematodes and other infectious pathogens, including
      viruses, represents a major cause of morbidity and mortality in Africa, South
      America and southeast Asia, as well as other parts of the world. Nitazoxanide is
      a member of the thiazolide class of drugs with a documented broad spectrum of
      activity against parasites and anaerobic bacteria. Moreover, the drug has
      recently been reported to have a profound activity against hepatitis C virus
      infection. In addition, nitazoxanide exhibits anti-inflammatory properties, which
      have prompted clinical investigations for its use in Crohn's disease. Studies
      with nitazoxanide derivatives have determined that there must be significantly
      different mechanisms of action acting on intracellular versus extracellular
      pathogens. An impressive number of clinical studies have shown that the drug has
      an excellent bioavailability in the gastrointestinal tract, is fast acting and
      highly effective against gastrointestinal bacteria, protozoa and helminthes. A
      recent Phase II study has demonstrated viral response (hepatitis C) to
      monotherapy, with a low toxicity and an excellent safety profile over 24 weeks of
      treatment. Pre-clinical studies have indicated that there is a potential for
      application of this drug against other diseases, not primarily affecting the
      liver or the gastrointestinal tract.

PMID- 16634718
TI  - Is NXY-059 an advancement in the treatment of acute ischaemic stroke?

PMID- 16634720
TI  - Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline
      release and neurocardiogenic syncope.
AB  - In patients with neurocardiogenic syncope, head-up tilt often evokes acute loss
      of consciousness accompanied by vasodilatation, increased plasma adrenaline and
      systemic hypotension. Since hypotension increases adrenaline levels and
      adrenaline can produce skeletal muscle vasodilatation by activating beta2
      receptors, adrenaline might induce a positive feedback loop precipitating
      circulatory collapse. We hypothesized that propranolol, a non-selective beta
      blocker, would prevent adrenaline-induced vasodilatation and thereby prevent
      syncope. Eight subjects with recurrent neurocardiogenic syncope and previously
      documented tilt-induced syncope with elevated plasma adrenaline levels
      participated in the present study. Subjects underwent tilt table testing after
      receiving oral propranolol or placebo in a double-blind randomized crossover
      fashion. Haemodynamic and neurochemical variables were measured using intra
      arterial monitoring, impedance cardiography, arterial blood sampling and tracer
      kinetics of simultaneously infused [3H]noradrenaline and [3H]adrenaline. The
      occurrence of tilt-induced neurally mediated hypotension and syncope, duration of
      tilt tolerance, extent of the decrease in SVRI (systemic vascular resistance
      index) and magnitude of plasma adrenaline increases did not differ between the
      propranolol and placebo treatment phases. SVRI was inversely associated with
      fractional increase in plasma adrenaline during both phases. One subject did not
      faint when on propranolol; this subject's response is discussed in the context of
      central effects of propranolol. In this small, but tightly controlled, study,
      propranolol did not prevent tilt-induced vasodilatation, syncope or elevated
      plasma adrenaline.

PMID- 16634721
TI  - Health system studies of pain in older adults: can we save the "golden years"?

PMID- 16634723
TI  - Sleep quality and the role of sleep medications for veterans with chronic pain.
AB  - OBJECTIVE: The purpose of this study was to investigate the nature of sleep
      problems in veterans presenting to a pain clinic, factors that predict likelihood
      of being prescribed a sleep medication, types of medications prescribed, and the
      relationships between sleep medication use and sleep quality, pain, and
      depression. DESIGN/SETTING/PATIENTS: Participants were 201 consecutive patients
      referred to a Veterans Affairs outpatient pain clinic. They were administered the
      Pittsburgh Sleep Quality Index, Multidimensional Pain Inventory, and Beck
      Depression Inventory at intake and 2-month follow-up. Sleep and opioid medication
      prescriptions were also monitored. RESULTS: Pain severity did not predict global
      sleep quality; global sleep quality was not predictive of pain severity. Greater
      depression predicted both more severe pain and more sleep impairment. Having
      previously been prescribed such medications was the only significant predictor of
      being prescribed a sleep medication at the time of the 2-month assessment. For
      the 45% of participants on sleep medications, these medications were not
      associated with any significant change in pain factors or depression. However,
      sleep medication use was associated with worse global sleep quality, sleep
      duration, and sleep efficiency. Opioid prescription was not a significant
      predictor of sleep factors, pain-related variables, or depression symptoms.
      DISCUSSION: Results suggest depression may contribute more significantly to sleep
      problems than pain-related variables in this population. The data suggest the
      need for controlled, prospective studies of sleep medication to further
      investigate the impact of sleep medications on sleep components in patients with
      chronic pain.

PMID- 16634724
TI  - Slow-frequency rTMS reduces fibromyalgia pain.
AB  - OBJECTIVE: Evidence suggests that fibromyalgia (FM) is a centrally mediated pain
      disorder. Antidepressants, including electroconvulsive therapy, provide some
      symptomatic relief in FM and other pain disorders. Repetitive transcranial
      magnetic stimulation (rTMS) is a new antidepressant treatment, which may also be
      useful in treating chronic pain. DESIGN: As part of a larger study, four women
      with depression, FM, and borderline personality disorder received 1-Hz rTMS
      applied to the right dorsolateral prefrontal cortex. Subjects rated pain using an
      11-point Likert scale. RESULTS: Pretreatment pain averaged 8.2 (7-9.5) and
      reduced to 1.5 (0-3.5) after treatment (P < 0.009). All had improvement in pain,
      and two had complete resolution of pain. Only one of the four subjects had an
      antidepressant response. CONCLUSIONS: These preliminary findings suggest a
      possible role for rTMS in treating FM.

PMID- 16634725
TI  - Understanding the provider contribution to race/ethnicity disparities in pain
      treatment: insights from dual process models of stereotyping.
AB  - OBJECTIVE: This article applied dual process models of stereotyping to illustrate
      how various psychological mechanisms may lead to unintentional provider bias in
      decisions about pain treatment. Stereotypes have been shown to influence
      judgments and behaviors by two distinct cognitive processes, automatic
      stereotyping and goal-modified stereotyping, which differ both in level of
      individual conscious control and how much they are influenced by the goals in an
      interaction. Although these two processes may occur simultaneously and are
      difficult to disentangle, the conceptual distinction is important because
      unintentional bias that results from goal-modified rather than automatic
      stereotyping requires different types of interventions. We proposed a series of
      hypotheses that showed how these different processes may lead providers to
      contribute to disparities in pain treatment: 1) indirectly, by influencing the
      content and affective tone of the clinical encounter; and 2) directly, by
      influencing provider decision making. We also highlighted situations that may
      increase the likelihood that stereotype-based bias will occur and suggested
      directions for future research and interventions.

PMID- 16634726
TI  - Lidocaine 5% patch: an open-label naturalistic chronic pain treatment trial and
      prediction of response.
AB  - OBJECTIVE: There have been a few open-label nonplacebo reports on the successful
      use of lidocaine 5% patch (L5P) for other types of pain besides postherpetic
      neuralgia, such as chronic low back pain. With the these reports, we began to
      utilize L5P routinely for chronic pain patients (CPPs) with various pain
      diagnoses. The purpose of this report was to describe the results of a
      retrospective review of this open-label naturalistic L5P chronic pain treatment
      trial and to attempt to delineate predictors of perceived clinical response.
      DESIGN: Consecutive CPPs were selected for this clinical trial according to the
      following inclusion criteria: the CPPs with pain greater than 6-month duration
      and either a hyperalgesic pain area or trigger point, which could be covered by
      one L5P, were offered a 3-day L5P naturalistic treatment trial. The purpose of
      this trial was to determine which CPPs would perceive improvement and continue
      using L5P. CPPs entering the trial completed the neuropathic pain scale (NPS) at
      entrance and completion of the trial. The senior author also completed a baseline
      information tool on each CPP entering this naturalistic trial. At the completion
      of the 3-day trial, the CPPs were asked if they perceived pain improvement with
      the use of L5P. In the retrospective review, the CPPs were thus segregated into
      two groups, those with and without perceived clinical improvement, and were
      statistically compared for available clinical variables. Logistic regression was
      then utilized to determine which significant independent variables contributed to
      the correct prediction of perceived improvement. SETTING: Multidisciplinary pain
      facility. PATIENTS: Patients with chronic pain. RESULTS: Of 362 consecutive CPPs,
      114 or 31.5% were deemed candidates for this naturalistic trial. None of the CPPs
      refused or fulfilled exclusion criteria eliminating them from the trial. The
      total sample (N = 114) showed statistical improvement on all 10 NPS scales
      (except scales 4 and 6) plus the NPS 4, NPS nonallodynic 8, and NPS 10. The
      perceived clinically improved group (N = 87, 76.3% of those entering the trial),
      also showed perceived improvement on all preceding scales except 4 and 6. The
      perceived clinically nonimproved group (N = 27, 23.7% of those entering the
      trial) showed statistical improvement on scales B and NPS 10. Perceived
      improvement was predicted by the following variables: pain wakes patient up,
      patch placement not low back, and not in litigation. These variables explained
      9.8%, 20%, and 14% of the variance, respectively. Overall, 44.5% of the variance
      was explained. CONCLUSIONS: A significant percentage of CPPs exposed to an L5P 3
      day naturalistic trial perceived clinical improvement. However, this can only be
      concluded as an initial effect, and whether or not this effect is attributable to
      L5P cannot be derived from our data as the effect could have been nonspecific.
      The apparent CPP perceived clinical improvement was not associated with any
      particular useful clinical indicator. As such, at present, no variable can be
      recommended for use in selecting CPPs for such a naturalistic L5P clinical
      treatment trial. However, this study indicates that such a trial can be useful in
      selecting CPPs who may perceive benefit from L5P.

PMID- 16634727
TI  - Low back pain in older adults: are we utilizing healthcare resources wisely?
AB  - OBJECTIVES: 1) To examine recent change in prevalence and Medicare-associated
      charges for non-invasive/minimally invasive evaluation and treatment of
      nonspecific low back pain (LBP); and 2) to examine magnetic resonance imaging
      (MRI) utilization appropriateness in older adults with chronic low back pain
      (CLBP). DESIGN: Two cross-sectional surveys of 1) national (1991-2002) and
      Pennsylvania (2000-2002) Medicare data; and 2) patients aged >or= 65 years with
      CLBP. SETTING: Outpatient data. PARTICIPANTS: Patients aged >or= 65 years with
      LBP. MEASUREMENTS: Study 1: Outpatient national and Pennsylvania Part A Medicare
      data were examined for number of patients and charges for all patients, and for
      those with nonspecific LBP. Total number of visits and charges for imaging
      studies, physical therapy (PT), and spinal injections was also examined for
      Pennsylvania. Study 2: 111 older adults with CLBP were interviewed regarding
      presence of red flags necessitating imaging and history of having a lumbar MRI,
      neurogenic claudication (NC), and back surgery. RESULTS: Study 1: Between 1991
      and 2002, there was a 42.5% increase in total Medicare patients, 131.7% increase
      in LBP patients, 310% increase in total charges, and 387.2% increase in LBP
      charges. In Pennsylvania (2000-2002), there was a 5.5% increase in LBP patients
      and 33.2% increase in charges (0.2% for PT, 59.4% for injections, 41.9% for
      MRI/CT, and 19.3% for X rays). Study 2: None of the 111 participants had red
      flags and 61% had undergone MRIs (29% with NC, 24% with failed back surgery
      syndrome). CONCLUSION: LBP documentation and diagnostic studies are increasing in
      Medicare beneficiaries, and evidence suggests that MRIs may often be ordered
      unnecessarily. Injection procedures appear to account for a significant
      proportion of LBP-associated costs. More studies are needed to examine the
      appropriateness with which imaging procedures and non-invasive/minimally invasive
      treatments are utilized, and their effect on patient outcomes.

PMID- 16634728
TI  - Older and younger adults in pain management programs in the United States:
      differences and similarities.
AB  - OBJECTIVES: 1) To investigate health status of older (>or=60 years) and younger
      adults (<60 years) with chronic pain and to separately compare that with existing
      normative data; and 2) to examine more fully differences in health status between
      younger and older adults with chronic pain and explore their geographic variation
      across three multidisciplinary pain programs in the Pacific, Mountain, and New
      England regions of the United States. DESIGN: We performed a cross-sectional
      analysis. PATIENTS: Initial assessments of 6,147 patients dating from January
      1998 to January 2003 were used. OUTCOMES MEASURES: We used the Treatment Outcomes
      of Pain Survey (TOPS), a disease-specific instrument that includes the Short Form
      36. RESULTS: The health status of the older pain patients in terms of their
      actual scores was comparable with that of younger pain patients across the three
      sites. Health status is impaired to a lesser degree in older than in younger
      adults with chronic pain as compared with normative adults. Statistically
      significant differences were found in a number of domains of the TOPS. Older
      adults with chronic pain present with pain intensity similar to that of younger
      patients with chronic pain, but report better mental health (P < 0.002), less
      fear-avoidance (P < 0.05), less passive coping (P < 0.0001), more life control (P
      < 0.05), and more lower body physical limitations (P < 0.005) than younger
      patients with chronic pain. CONCLUSIONS: Older adults with chronic pain differ in
      a number of important domains from younger adults with chronic pain: overall the
      former present with greater physical, and less psychosocial impairment.

PMID- 16634729
TI  - Withdrawal symptoms from transdermal fentanyl (TDF) after an allogeneic
      peripheral blood stem cell transplant (PBSCT).
AB  - A 47-year-old woman who underwent allogenic peripheral blood stem cell transplant
      developed withdrawal symptoms soon after Fentanyl 25 mcg/h patch was stopped,
      which has not been reported at this dose. Possible causes, such as the inhibition
      of CYP3A4 induced by cyclosporine causing elevations of serum fentanyl, are
      discussed.

PMID- 16634730
TI  - Beneficial effect of low-dose ketamine addition to epidural administration of
      morphine-bupivacaine mixture for cancer pain in two cases.
AB  - Two patients experiencing cancer pain with neuropathic components were treated
      with epidural administration of a mixture of ketamine (1 mg/mL) + morphine (1
      mg/mL) + bupivacaine (1 mg/mL) injected daily by epidural port. No serious
      adverse effect was observed throughout the therapy. The patients were mostly pain
      free and have gotten better quality of life during 110- and 48-day follow-up when
      the therapy was given by epidural route. Low doses of epidural ketamine added to
      morphine and bupivacaine increase the mean duration of satisfactory analgesia
      without severe adverse effects and restore quality of life when traditional
      therapy fails.

PMID- 16634732
TI  - Universal precautions: a matter of mutual trust and responsibility.

PMID- 16634734
TI  - Abnormal hemostasis tests and bleeding in chronic liver disease: are they
      related? Yes.

PMID- 16634735
TI  - Abnormal hemostasis tests and bleeding in chronic liver disease: are they
      related? No.

PMID- 16634736
TI  - Diagnosis and management of subsegmental pulmonary embolism.
AB  - INTRODUCTION: Although the advent of multi-detector row computed tomography (CT)
      has enabled better visualization of subsegmental pulmonary (SSP) arteries, SSP
      embolism is of uncertain clinical significance. We aimed at answering the
      following questions: Is spiral CT an accurate method to detect SSP embolism? How
      are subsegmental perfusion defects managed in outcome studies including spiral
      CT? What are the main characteristics and outcomes of patients in whom CT detects
      isolated subsegmental defects? METHODS: We performed a Medline search on July 1,
      2004, using the keywords 'pulmonary embolism' and 'computed tomography'. We
      limited our search to English language prospective studies comparing CT to
      pulmonary angiography, and to prospective outcome studies including CT in a
      diagnostic strategy, with at least a 3-month follow-up. RESULTS: Fourteen studies
      comparing CT to pulmonary angiography, and five prospective management studies
      using CT were retrieved. The sensitivity of single-detector CT for detecting
      subsegmental defects compared with pulmonary angiography was low (25%). The
      proportion of isolated SSP images was significantly higher in management studies
      using multi-detector CT (17 of 770 scans, 2.2%) compared with those using single
      detector CT (22 of 2232, 1.0%; P = 0.01). No straightforward attitude regarding
      anticoagulation therapy for isolated subsegmental defects emerged from the
      available literature. Finally, important clinical differences were found between
      patients having subsegmental and segmental or more proximal defects. CONCLUSIONS:
      These findings underline the uncertainty regarding the clinical significance of
      SSP embolism, and the management of patients with such findings.

PMID- 16634737
TI  - Ten years after...

PMID- 16634738
TI  - Post-thrombotic syndrome, recurrence, and death 10 years after the first episode
      of venous thromboembolism treated with warfarin for 6 weeks or 6 months.
AB  - BACKGROUND: The influence of the duration of anticoagulant therapy after venous
      thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM:
      To investigate the long-term sequelae of VTE in patients randomized to different
      duration of secondary prophylaxis. METHODS: In a multicenter trial comparing
      secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we
      extended the originally planned 2 years follow-up to 10 years. The patients had
      annual visits and at the last visit clinical assessment of the post-thrombotic
      syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a
      radiologist, blinded to treatment allocation. Causes of death were obtained from
      the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be
      evaluated at the 10 years follow-up. The probability of developing severe PTS was
      6% and any sign of PTS was seen in 56.3% of the evaluated patients. In
      multivariate analysis, old age and signs of impaired circulation at discharge
      from the hospital were independent risk factors at baseline for development of
      PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients
      with a higher rate among males, older patients, those with permanent triggering
      risk factor - especially with venous insufficiency at baseline - signs of
      impaired venous circulation at discharge, proximal deep vein thrombosis, or
      pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than
      expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58),
      mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI
      1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56).
      The duration of anticoagulation did not have a statistically significant effect
      on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during
      10 years after the first episode of VTE is high and not reduced by extension of
      secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence
      of VTE as well as mortality from arterial disease is needed.

PMID- 16634739
TI  - Genetic variation in basal and endotoxin-induced tissue factor expression in
      vivo.

PMID- 16634740
TI  - Polymorphism in the tissue factor region is associated with basal but not
      endotoxin-induced tissue factor-mRNA levels in leukocytes.
AB  - OBJECTIVE: Tissue factor (TF) plays a central role during disseminated
      intravascular coagulation (DIC) in sepsis. We hypothesized that a frequent D/I
      polymorphism, at nucleotide position -1208 in the promoter region, could
      influence TF-mRNA and downstream coagulation. METHODS: Basal- and
      lipopolysaccharide (LPS)-induced TF-mRNA expression, microparticle-associated TF
      procoagulant activity and coagulation were determined in healthy men (n = 74)
      before and after endotoxin (LPS) infusion (2 ng kg(-1)). Basal values of TF-mRNA
      ranged between 34 and > 37.5 cycles. RESULTS: Baseline TF-mRNA levels
      significantly differed between genotypes: I/I carriers had almost 2-fold higher
      TF-mRNA levels compared to D/D carriers at baseline (P < 0.01). In accordance,
      higher levels of microparticle-associated TF-procoagulant activity could be seen
      in I/I carriers. However, the genotype did not affect basal or LPS-induced levels
      of prothrombin fragment F1+2, D-dimer or cytokines including tumor necrosis
      factor and interleukin-6. CONCLUSION: The TF-1208 polymorphism is functional in
      that it regulates basal TF-mRNA in circulating monocytes and circulating
      microparticle-associated TF-procoagulant activity in vivo, but does not influence
      the relative increase in TF-mRNA or coagulation activation during low-grade
      endotoxemia.

PMID- 16634741
TI  - Activated partial thromboplastin time (APTT). New indications for an old test?

PMID- 16634742
TI  - Prediction of recurrent venous thromboembolism by the activated partial
      thromboplastin time.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a multi-factorial disease. Extensive
      thrombophilia screening is costly and often inconclusive. Simple laboratory
      methods are required to predict the risk of recurrence. OBJECTIVE: To assess if
      measurement of activated partial thromboplastin time (APTT) allows stratification
      of patients with VTE into high- and low-risk categories with regard to
      recurrence. PATIENTS AND METHODS: We prospectively followed 918 patients with a
      first unprovoked VTE and studied the relationship between recurrence and an APTT
      after discontinuation of anticoagulation. APTT was expressed as a ratio of test
      to reference coagulation times. Study endpoint was symptomatic recurrent VTE.
      RESULTS: Venous thromboembolism recurred in 101 (11%) patients. Patients without
      recurrence had a greater APTT ratio than those with recurrence (0.97 +/- 0.09 vs.
      0.93 +/- 0.09, P = 0.001). After 4 years, probability of recurrent VTE was 8.5%
      (95% CI: 5.5-11.5%) among patients with a ratio equal to or > 0.95 and 15.6% (95%
      CI: 11.4-19.9%) among patients with a lower ratio (P = 0.005). Compared with
      patients with an APTT ratio < 0.95, the relative risk (RR) of recurrence among
      patients with a ratio equal to or > 0.95 was 0.56 (95% CI: 0.38-0.84, P = 0.005)
      before and 0.58 (95% CI: 0.39-0.87, P = 0.009) after adjustment for sex, age,
      factor V Leiden, and factor II G20210A. CONCLUSIONS: Measurement of APTT allows
      stratification of patients with VTE into high- and low-risk categories with
      regard to recurrence.

PMID- 16634743
TI  - Heparin-induced immune thrombocytopenia - a clinical or laboratory diagnosis?

PMID- 16634744
TI  - Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced
      thrombocytopenia in two clinical settings.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse
      drug reaction caused by heparin. As thrombocytopenia is common in hospitalized
      patients receiving heparin, it would be useful to have a clinical scoring system
      that could differentiate patients with HIT from those with other reasons for
      thrombocytopenia. AIM: To compare prospectively the diagnostic utility of a
      clinical score for HIT in two different clinical settings. METHODS: The pretest
      clinical scoring system, the '4 T's', was used to classify 100 consecutive
      patients referred for possible HIT in one hospital (Hamilton General Hospital,
      HGH) into high, intermediate, and low probability groups. This system was also
      used to classify likewise 236 patients by clinicians in Germany referring blood
      for diagnostic testing for HIT in Greifswald (GW). The clinical scores were
      correlated with the results of laboratory testing for HIT antibodies using the
      serologic criteria for HIT with high diagnostic specificity. RESULTS: In both
      centers, patients with low scores were unlikely to test positive for HIT
      antibodies [HGH: 1/64 (1.6%), GW: 0/55 (0%)]. Patients with intermediate [HGH:
      8/28 (28.6%), GW: 11/139 (7.9%)] or high scores [HGH: 8/8 (100%), GW: 9/42
      (21.4%)] were more likely to test positive for clinically significant HIT
      antibodies. The positive predictive value of an intermediate or high clinical
      score for clinically significant HIT antibodies was higher at one center (HGH).
      CONCLUSIONS: A low pretest clinical score for HIT seems to be suitable for ruling
      out HIT in most situations (high-negative predictive value). The implications of
      an intermediate or high score vary in different clinical settings.

PMID- 16634745
TI  - A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease:
      results from a multicenter European study (MCMDM-1 VWD).
AB  - BACKGROUND: A quantitative description of bleeding symptoms in type 1 von
      Willebrand disease (VWD) has never been reported. OBJECTIVES: The aim was to
      quantitatively evaluate the severity of bleeding symptoms in type 1 VWD and its
      correlation with clinical and laboratory features. PATIENTS AND METHODS: Bleeding
      symptoms were retrospectively recorded in a European cohort of VWD type 1
      families, and for each subject a quantitative bleeding score (BS) was obtained
      together with phenotypic tests. RESULTS: A total of 712 subjects belonging to 144
      families and 195 controls were available for analysis. The BS was higher in index
      cases than in affected family members (BS 9 vs. 5, P < 0.0001) and in unaffected
      family members than in controls (BS 0 vs. -1, P < 0.0001). There was no effect of
      ABO blood group. BS showed a strong significant inverse relation with either von
      Willebrand ristocetin cofactor (VWF:RCo), von Willebrand antigen (VWF:Ag) or
      factor VIII procoagulant activity (FVIII:C) measured at time of enrollment, even
      after adjustment for age, sex and blood group (P < 0.001 for all the four upper
      quintiles of BS vs. the first quintile, for either VWF:RCo, VWF:Ag or FVIII:C).
      Higher BS was related with increasing likelihood of VWD, and a mucocutaneous BS
      (computed from spontaneous, mucocutaneous symptoms) was strongly associated with
      bleeding after surgery or tooth extraction. CONCLUSIONS: Quantitative analysis of
      bleeding symptoms is potentially useful for a more accurate diagnosis of type 1
      VWD and to develop guidelines for its optimal treatment.

PMID- 16634746
TI  - Linkage analysis in families diagnosed with type 1 von Willebrand disease in the
      European study, molecular and clinical markers for the diagnosis and management
      of type 1 VWD.
AB  - BACKGROUND: von Willebrand disease (VWD) type 1 is a congenital bleeding disorder
      caused by genetic defects in the von Willebrand factor (VWF) gene and
      characterized by a reduction of structurally normal VWF. The diagnosis of type 1
      VWD is difficult because of clinical and laboratory variability. Furthermore,
      inconsistency of linkage between type 1 VWD and the VWF locus has been reported.
      OBJECTIVES: To estimate the proportion of type 1 VWD that is linked to the VWF
      gene. PATIENTS AND METHODS: Type 1 VWD families and healthy control individuals
      were recruited. An extensive questionnaire on bleeding symptoms was completed and
      phenotypic tests were performed. Linkage between VWF gene haplotypes and the
      diagnosis of type 1 VWD, the plasma levels of VWF and the severity of bleeding
      symptoms was analyzed. RESULTS: Segregation analysis in 143 families diagnosed
      with type 1 VWD fitted a model of autosomal dominant inheritance. Linkage
      analysis under heterogeneity resulted in a summed lod score of 23.2 with an
      estimated proportion of linkage of 0.70. After exclusion of families with
      abnormal multimer patterns the linkage proportion was 0.46. LOD scores and
      linkage proportions were higher in families with more severe phenotypes and with
      phenotypes suggestive of qualitative VWF defects. About 40% of the total
      variation of VWF antigen could be attributed to the VWF gene. CONCLUSIONS: We
      conclude that the diagnosis of type 1 VWD is linked to the VWF gene in about 70%
      of families, however after exclusion of qualitative defects this is about 50%.

PMID- 16634747
TI  - Genetic linkage and association analysis in type 1 von Willebrand disease:
      results from the Canadian type 1 VWD study.
AB  - BACKGROUND: von Willebrand disease (VWD) is the most common bleeding disorder
      known in humans, with type 1 VWD representing the majority of cases. Unlike the
      other variant forms of VWD, type 1 disease represents a complex genetic trait,
      influenced by both genetic and environmental factors. AIM: To evaluate the
      contribution of the von Willebrand factor (VWF) and ABO blood group loci to the
      type 1 VWD phenotype, and to assess the potential for locus heterogeneity in this
      condition, we have performed genetic linkage and association studies on a large,
      unselected type 1 VWD population. METHOD: We initially collected samples from 194
      Canadian type 1 VWD families for analysis. After the exclusion of families found
      to have either type 2 or type 3 VWD, and pedigrees with samples from single
      generations, linkage and association analysis was performed on 155 type 1 VWD
      families. RESULTS AND CONCLUSION: The linkage study has shown a low heterogeneity
      LOD score of 2.13 with the proportion of families linked to the VWF gene
      estimated to be 0.41. Linkage was not detected to the ABO locus in this type 1
      VWD population. In the family-based association test, significant association was
      found between the type 1 VWD phenotype, the quantitative traits, VWF:Ag, VWF:RCo,
      and FVIII:C and the ABO 'O' and 'A' alleles and the VWF codon 1584 variant. There
      was also weak association with the -1185 promoter polymorphism and VWF:Ag,
      VWF:RCo, and FVIII:C plasma levels. These studies provide further evidence to
      support the role for genetic loci other than VWF and ABO in the pathogenesis of
      type 1 VWD.

PMID- 16634748
TI  - Hyperhomocysteinemia and low B vitamin levels are independently associated with
      venous thromboembolism: results from the EDITH study: a hospital-based case
      control study.
AB  - BACKGROUND: Moderate hyperhomocysteinemia and B vitamins deficiency are thought
      to be risk factors for venous thromboembolism (VTE). The causality and
      independence of those associations are still questioned. METHODS: We measured
      fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10
      methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients
      hospitalized with a first well-documented deep vein thrombosis and/or pulmonary
      embolism not related to a major acquired risk factor and 467 controls matched for
      gender and age. RESULTS: Mild hyperhomocysteinemia, low serum folates, and
      vitamin B12 were associated with VTE independently of each other. In multivariate
      analysis, odds ratios (OR) (95% CI) for VTE associated with mild
      hyperhomocysteinemia (>15 micromol L(-1)), low serum folates (< or = 4.9 nmol L(
      1)), and vitamin B12 (< or = 253 pmol L(-1)) were 1.48 (1.05-2.08), 3.14 (1.35
      7.32) and 1.42 (1.03-1.98), respectively. An MTHFRC677T genotype was not
      significantly associated with VTE; OR (95% CI): 1.13 (0.70-1.81) CONCLUSIONS: The
      current data provides further knowledge in the complex relationship between
      hyperhomocysteinemia, low vitamin levels, and VTE.

PMID- 16634749
TI  - The utility of quantitative calf muscle near-infrared spectroscopy in the follow
      up of acute deep vein thrombosis.
AB  - BACKGROUND: To investigate patterns of venous insufficiency and changes in calf
      muscle deoxygenated hemoglobin (HHb) levels after an acute deep vein thrombosis
      (DVT). METHODS: A total of 78 limbs with an acute DVT involving 156 anatomic
      segments were evaluated with duplex scanning and near-infrared spectroscopy
      (NIRS) at 1, 3, 6 and 12 months. Venous segments were examined whether they were
      occluded, partially recanalized, and totally recanalized, and the development of
      venous reflux was noted. The NIRS was used to measure calf muscle HHb levels.
      Calf venous blood filling index (HHbFI) was calculated on standing, then the calf
      venous ejection index (HHbEI), and the venous retention index (HHbRI) were
      obtained after exercise. RESULTS: The segments investigated were the common
      femoral vein (CFV; 38 segments), femoral vein (FV; 37), popliteal vein (POPV;
      44), and calf veins (CV; 37). At 1 year, thrombi had fully resolved in 67% of the
      segments, 27% remained partially recanalized, 6% were occluded. The venous
      occlusion was predominant in the FV (24%) at 1 year. On the contrary, rapid
      recanalization was obtained in CV than proximal veins at each examination (P <
      0.01). Venous reflux was predominant in POPV (55%), followed by FV (19%), and no
      reflux was found in CV. At 1 year, the HHbFI in POPV reflux patients was
      significantly higher than those with resolution (0.19 +/- 0.14, 0.11 +/- 0.05
      microm s, P = 0.009, respectively). Similarly, there was a significant difference
      in the HHbRI between the two groups (3.08 +/- 1.91, 1.42 +/- 1.56, P = 0.002,
      respectively). In patients with FV occlusion, the value of HHbRI was
      significantly higher than those with complete resolution (2.59 +/- 1.50, 1.42 +/-
      1.56, P = 0.011, respectively). CONCLUSIONS: The lower extremity venous segments
      show different proportions of occlusion, partial recanalization, and total
      recanalization. The CV shows more rapid recanalization than proximal veins. The
      NIRS-derived HHbFI and HHbRI could be promising parameters as the overall venous
      function in the follow-up of acute DVT. These findings might be very helpful for
      physician in detecting patients who require much longer follow-up studies.

PMID- 16634750
TI  - High sensitivity with color duplex sonography in thrombosis screening after ankle
      fracture surgery.
AB  - BACKGROUND: Phlebography is regarded as the reference standard for diagnosing
      asymptomatic deep vein thrombosis (DVT) in studies of thromboprophylaxis.
      However, technical advances with noninvasive color duplex sonography (CDS) have
      made this procedure an interesting alternative. OBJECTIVES: The objective of the
      present prospective study was to compare the sensitivity and specificity of CDS
      with those of phlebography. PATIENTS: The first 180 consecutive patients included
      in a larger randomized trial for prolonged thromboprophylaxis were subject to
      unilateral CDS and to phlebography after ankle fracture surgery. The patients
      were examined 6 weeks after surgery, all examinations being evaluated blindly.
      After patient drop outs and exclusions, 144 patients were left for analysis.
      RESULTS: Phlebography and CDS examinations were inconclusive or were not
      completed for 19% of these patients (28/144). DVT was diagnosed by phlebography
      in 21% (24/116) of the remaining patients. Most of the thrombi were isolated calf
      DVTs (18/24). In contrast, DVT was diagnosed by CDS in 31% of these patients
      (36/116): only one case diagnosed by phlebography was missed by CDS. The
      specificity of CDS is thus 86% and its sensitivity is 96%. The positive
      predictive value is 64%, and the negative predictive value is 99%. CONCLUSIONS:
      CDS is a safe method for detecting asymptomatic distal DVT. It has a high
      sensitivity and high negative predictive value, which means that the method is
      highly reliable to rule out DVT. Our results indicate that CDS could be
      considered as an alternative method for DVT screening.

PMID- 16634751
TI  - Biological effects of aspirin and clopidogrel in a randomized cross-over study in
      96 healthy volunteers.
AB  - BACKGROUND: Some data suggest that biological 'resistance' to aspirin or
      clopidogrel may influence clinical outcome. OBJECTIVE: The aim of this study was
      to evaluate the relationship between aspirin and clopidogrel responsiveness in
      healthy subjects. METHODS: Ninety-six healthy subjects were randomly assigned to
      receive a 1-week course of aspirin 100 mg day(-1) followed by a 1-week course of
      clopidogrel (300 mg on day 1, then 75 mg day(-1)), or the reverse sequence,
      separated by a 2-week wash-out period. The drug effects were assessed by means of
      serum TxB2 assay, platelet aggregation tests, and the PFA -100 and Ultegra RPFA 
      Verify Now methods. RESULTS: Only one subject had true aspirin resistance,
      defined as a serum TxB2 level > 80 pg microL(-1) at the end of aspirin
      administration and confirmed by platelet incubation with aspirin. PFA-100 values
      were normal in 29% of the subjects after aspirin intake, despite a drastic
      reduction in TxB2 production; these subjects were considered to have aspirin
      pseudo-resistance. Clopidogrel responsiveness was not related to aspirin pseudo
      resistance. Selected polymorphisms of platelet receptor genes were not associated
      with either aspirin or clopidogrel responsiveness. CONCLUSIONS: In healthy
      subjects, true aspirin resistance is rare and aspirin pseudo-resistance is not
      related to clopidogrel responsiveness.

PMID- 16634752
TI  - Phospholipid composition controls thromboplastin sensitivity to individual
      clotting factors.
AB  - BACKGROUND: Tissue factor is the active ingredient in thromboplastin reagents
      used to perform prothrombin time (PT) clotting tests to monitor oral
      anticoagulant therapy and to screen for clotting factor deficiencies.
      Thromboplastins are complex mixtures prepared from extracts of brain or placenta,
      although newer thromboplastins contain recombinant tissue factor incorporated
      into phospholipid vesicles. Thromboplastins can vary widely in their sensitivity
      to reductions in the levels of vitamin K-dependent clotting factors. A system to
      compensate for this, the International Sensitivity Index (ISI) and International
      Normalized Ratio (INR), has revolutionized the monitoring of oral anticoagulant
      therapy. The INR system is also sometimes used to monitor coagulopathies in
      patients with sepsis or liver failure, applications for which it was not
      originally designed and for which it has not been rigorously validated.
      OBJECTIVES: To better understand thromboplastin performance, we systematically
      investigated which properties of recombinant thromboplastins influence their
      sensitivities to changes in the levels of specific clotting factors. RESULTS: We
      now report that relative sensitivities to changes in the plasma levels of factors
      V, VII, X (FV, FVII, FX) and prothrombin are differentially influenced by a
      recombinant thromboplastin's content of phospholipid and sodium chloride.
      Furthermore, thromboplastins of similar ISI values may exhibit quite different
      sensitivities to each of these clotting factors. CONCLUSIONS: Differing
      sensitivities of thromboplastin reagents to individual clotting factor levels
      have implications for monitoring of oral anticoagulant therapy and interpreting
      results of the PT assay.

PMID- 16634753
TI  - Accuracy of FVIII: C assay by one-stage method can be improved using hemophilic
      plasma as diluent.
AB  - BACKGROUND: the basic prerequisite of Factor VIII clotting assay (FVIII:C) by One
      Stage Method is that all other than FVIII clotting factors are present in
      constant concentration in each dilution of both standard reference and patient's
      plasma curves. On the contrary, the plasma content of each dilution is decreasing
      as the dilution factor increases. OBJECTIVES AND METHODS: to keep exactly
      constant the plasma content in each mixture, we performed all dilutions of both
      standard reference and patient's plasma with FVIII deficient plasma and further
      with a fixed amount of buffer (method B). To show the discrepancies between this
      method and regular method A, using buffer to make dilutions, a comparative study
      was conducted on FVIII: C assay on samples at known FVIII concentration and in
      patients' plasma. Imidazole or Owren's buffers and five different aPTT reagents
      were employed, both in method A and B. RESULTS: a discrepancy between FVIII: C
      assays obtained by method A and B was observed, mainly when Pathrontin SL and
      Imidazole buffer were used. The assays derived from method B always better fit
      with the expected, calculated, values of FVIII:C concentrations. Furthermore,
      FVIII: C was assayed in 60 patients: the outcome of method A was always higher
      than values of method B. The discrepancy between the two methods was higher at
      FVIII concentrations below 50 U/dL but null at 100 U/dL. The A slope was steeper
      than B slope and the difference was statistically significant starting from the
      1/10 dilution. Accordingly, FVIII: C of patients' plasma obtained by method A was
      always higher that those obtained by method B, even 2 or 3 times for FVIII level
      < or = 10 U/dL or 1.4-1.6 times for FVIII levels between 10 and 25 U/dL.
      CONCLUSIONS: only method B is able to give FVIII: C assays in agreement with the
      expected values. The dilution of reference standards and samples with FVIII
      deficient plasma is crucial to accurately evaluate the post-infusion FVIII
      concentrations in pharmacokinetic studies or the trough level during prophylactic
      therapy and to investigate the discrepancy among different FVIII: C assays. In
      addition, the assessment of severity and classification of hemophilia should be
      reviewed.

PMID- 16634754
TI  - Inhibitors of blood coagulation factors Xa and IIa synergize to reduce thrombus
      weight and thrombin generation in vivo and in vitro.
AB  - BACKGROUND: Many compounds currently in development for treatment of thrombotic
      disorders demonstrate high specificity for single targets of blood coagulation
      such as factor Xa (FXa) or thrombin. AIM: The aim of this study is to determine
      if inhibition of both FXa and thrombin by simultaneous administration of
      PD0313052 and argatroban, respectively, synergistically increases the effect of
      either drug alone in vivo and in vitro. METHODS AND RESULTS: Analyses of thrombin
      generation from combined inhibition in human plasma using statistical methods of
      Bliss independence identified a synergistic reduction in thrombin production 30%
      lower than predicted by simple additivity. The greatest synergy occurred at
      concentrations of each compound below their individual IC50 values. In a rabbit
      arterio-venous shunt model (RAV) of thrombosis, co-administration of PD0313052
      and argatroban reduced thrombus weight (TW) to a much greater degree than
      expected by additivity alone producing a synergistic decrease of 45% over the
      level predicted by additivity. Analyses of thrombin generation in plasma samples
      from the RAV also demonstrated 38% synergy ex vivo. Furthermore, at plasma
      concentrations with the greatest synergistic effect, no increase in bleeding or
      appreciable change in prothrombin time, activated partial thromboplastin time, or
      activated clotting time was observed, but thrombus weight reduction was greater
      than twofold higher than that expected from simple additivity. CONCLUSIONS: These
      results demonstrate a significant synergistic antithrombotic effect of combining
      low doses of PD0313052 and argatroban and support the hypothesis that
      simultaneous targeting of multiple coagulation enzymes may offer an improved
      therapeutic index in the prevention and treatment of thrombosis.

PMID- 16634755
TI  - Epitope mapping factor VIII A2 domain by affinity-directed mass spectrometry:
      residues 497-510 and 584-593 comprise a discontinuous epitope for the monoclonal
      antibody R8B12.
AB  - The murine monoclonal antibody R8B12 recognizes the C-terminal region (residues
      563-740) of the A2 subunit of factor VIIIa [J Biol Chem 266: 1991; p. 20139], as
      judged by Western blotting. However, the location of the epitope within this
      region is not known. In the present study, we used affinity-directed mass
      spectrometry to map the epitope. A2 subunit was digested with trypsin or
      chymotrypsin and then subjected to immunoprecipitation (IP) using R8B12 IgG.
      Masses of the affinity-selected peptides were determined directly from the immune
      complexes by matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS). Proteolysis of A2 with the two proteases generated a pre-IP peptide
      fingerprint that covered approximately 70% of the A2 domain sequence. Analysis of
      the post-IP tryptic peptide fingerprint showed two masses, 1309 and 1653 Da
      representing residues 584-593 and 497-510, respectively, determined from a
      theoretical database search and confirmed by direct sequencing. Results using a
      chymotryptic digest yielded a single, weakly reactive fragment consistent with
      residues 577-586, suggesting the importance of residues Ser584-Tyr586 in forming
      the epitope. A synthetic peptide to residues 584-593 was immunoprecipitated by
      the IgG and blocked R8B12-directed blotting to A2 subunit. The 497-510 and 584
      593 segments were observed to be adjacent and surface exposed in the A2 domain
      model, and together with the above results suggest that A2 domain residues 497
      510 and 584-593 represent a discontinuous epitope for R8B12. Furthermore, based
      upon blotting specificity, we speculate that residues 584-593 make a
      substantially greater contribution to the binding energy for this interaction.

PMID- 16634756
TI  - Cord blood in vitro expanded CD41 cells: identification of novel components of
      megakaryocytopoiesis.
AB  - BACKGROUND: Megakaryopoiesis represents a multi-step, often unclear, process
      leading to commitment, differentiation, and maturation of megakaryocytes (MKs)
      that release platelets. AIM: To identify the novel genes that might help to
      clarify the molecular mechanisms of megakaryocytopoiesis and be regarded as
      potential candidates of inherited platelet defects, global gene expression of
      hematopoietic lineages was carried out. METHODS: Human cord blood was used to
      purify CD34+ stem cells and in vitro expand CD41+ cells and burst-forming unit
      erythroid (BFU-E). We investigated the expression profiles of these three
      hematopoietic lineages in the Affymetrix system and selected genes specifically
      expressed in MKs by comparing transcripts of the different lineages using the
      dchip and pam algorithms. RESULTS: A detailed characterization of MK population
      showed that 99% of cells expressed the CD41 antigen whereas 73% were recognizable
      as terminally differentiated fetal MKs. The profile of these cells was compared
      with that of CD34+ cells and BFU-E allowing us to select 70 transcripts (MK
      core), which represent not only the genes with a well-known function in MKs, but
      also novel genes never detected or characterized in these cells. Moreover, the
      specific expression was confirmed at both RNA and protein levels, thus validating
      the 'MK-core' isolated by informatics tools. CONCLUSIONS: This is a global gene
      expression that for the first time depicts a well-characterized population of
      cord blood-derived fetal MKs. Novel genes have been detected, such as those
      encoding components of the extracellular matrix and basal membrane, which have
      been found in the cytoplasm of Mks, suggesting that new physiological aspects of
      MKs should be studied.

PMID- 16634757
TI  - (N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces
      rapid desensitization of the P2Y1 receptor of human platelets.
AB  - Adenosine diphosphate (ADP) initiates and maintains sustained aggregation of
      platelets through simultaneous activation of both the Gq-coupled P2Y1 receptor
      and the Gi-coupled P2Y12 receptor. We recently described the synthesis and P2Y1
      receptor-specific agonist activity of (N)-methanocarba-2MeSADP (MRS2365).
      Consequences of selective activation of the P2Y1 receptor by MRS2365 have been
      further examined in human platelets. Whereas MRS2365 alone only induced shape
      change, addition of MRS2365 following epinephrine treatment, which activates the
      Gi/z-linked, alpha2A-adrenergic receptor, resulted in sustained aggregation that
      was indistinguishable from that observed with ADP. Conversely, the platelet shape
      change promoted by ADP in the presence of the GPIIb/IIIa antagonist eptifibatide
      was similar to that promoted by MRS2365. Preaddition of the high affinity P2Y1
      receptor antagonist MRS2500 inhibited the effect of MRS2365, whereas addition of
      MRS2500 subsequent to MRS2365 reversed the MRS2365-induced shape change.
      Preactivation of the P2Y1 receptor with MRS2365 for 2 min resulted in marked loss
      of capacity of ADP to induce aggregation as evidenced by a greater than 20-fold
      rightward shift in the concentration effect curve of ADP. This inhibitory effect
      of P2Y1 receptor activation was dependent on the concentration of MRS2365 (EC50 =
      34 nm). The inhibitory effect of preincubation with MRS2365 was circumvented by
      activation of the Gq-coupled 5-HT2A receptor suggesting that MRS2365 induces loss
      of the ADP response as a consequence of desensitization of the Gq-coupled P2Y1
      receptor. The time course of MRS2365-induced loss of aggregation response to
      epinephrine was similar to that observed with ADP. These results further
      demonstrate the P2Y1 receptor selectivity of MRS2365 and illustrate the
      occurrence of agonist-induced desensitization of the P2Y1 receptor of human
      platelets studied in the absence of P2Y12 receptor activation .

PMID- 16634758
TI  - Platelet-lymphocyte conjugation differs between lymphocyte subpopulations.
AB  - BACKGROUND: Platelets can bind to, and thereby influence, lymphocyte function.
      OBJECTIVE: The propensities of different lymphocyte subpopulations to form
      platelet-lymphocyte conjugates/aggregates (P-Lym) was investigated using four
      color whole blood flow cytometry. RESULTS: P-Lym constituted approximately 3% of
      circulating lymphocytes. Platelet conjugation was most common among large
      (monocyte-sized) lymphocytes. Platelet activation by ADP slightly increased
      platelet-T-cell conjugation, mainly to T-cytolytic (Tc) cells, but markedly
      elevated platelet-natural killer (NK)-cell conjugation. T-cell activation by
      phytohemagglutinin increased heterotypic conjugation among both T-helper (TH) and
      Tc cells, whilst NK-cell activation by interleukin-2 affected platelet-NK-cell
      aggregation little. Neither platelet activation nor lipopolysaccharides-induced B
      cell activation enhanced platelet-B-cell aggregation. Activation-dependent
      heterotypic conjugation was mainly found among large cells, with increased
      percentages of conjugated cells and more platelets bound per lymphocyte. P-Lym
      formation initiated by platelet activation was abolished by P-selectin blockade,
      and tended to be reduced by inhibition of GPIIb/IIIa, CD11b, or CD40L. P-Lym
      formation initiated by lymphocyte activation was partially inhibited by each of
      these blocking agents, but more markedly inhibited when the blocking agents were
      combined. CONCLUSIONS: Platelets selectively bind to larger and activated
      lymphocytes. T-lymphocyte activation enhances platelet-T-cell aggregation.
      Platelet activation enhances platelet-Tc aggregation slightly and platelet-NK
      cell aggregation markedly, while cellular activation affects platelet-B-cell
      aggregation little. P-selectin ligation is essential, but GPIIb/IIIa, CD40L, and
      CD11b also contribute to the heterotypic conjugation.

PMID- 16634759
TI  - P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation.
AB  - P2X1 receptors are ATP-gated channel demonstrated to be involved in multiple
      platelet responses, although in vitro analysis has been complicated by the
      effects of rapid desensitization. To further investigate potential roles of P2X1
      receptors in platelet activation, the current study employed methods which
      maximally preserved P2X1 functionality. In preliminary in vivo studies, P2X1
      deficiency reduced thrombus formation following the laser-induced, but not FeCl3
      induced injury. Given the multiple potential mechanisms involved in thrombus
      formation in vivo, including tissue-factor/thrombin generation pathways,
      subsequent studies were designed to investigate the effects of P2X1 inhibition or
      stimulation on platelet activation in vitro; specifically, the interaction of
      P2X1 with thrombin receptor stimulation. Aggregation initiated by low/threshold
      levels of a protease-activated receptor (PAR)4 agonist was reduced in P2X1
      deficient murine platelets, and inhibition of P2X1 in wild-type platelets
      similarly reduced PAR4-mediated aggregation. In human platelets, aggregation to
      low/threshold stimulation of PAR1 was inhibited with the P2X1 antagonist MRS2159.
      In addition, P2X1 stimulation primed human platelet responses, such that
      subsequent sub-threshold PAR1 responses were converted into significant
      aggregation. Selective ADP receptor inhibitors attenuated P2X1-mediated priming,
      suggesting that the synergy between P2X1 and sub-threshold PAR1 stimulation was
      in part because of enhanced granular release of ADP. Overall, the present study
      defines a novel interaction between platelet P2X1 and thrombin receptors, with
      P2X1 functioning to amplify aggregation responses at low levels of thrombin
      receptor stimulation.

PMID- 16634760
TI  - 2B or not 2B? What is the role of VWF in platelet-matrix interactions? And what
      is the role of the VWF:CB in VWD diagnostics? These are the questions.

PMID- 16634761
TI  - Should vitamin K be administered when HIT is diagnosed after administration of
      coumarin?

PMID- 16634762
TI  - The natural course of women with recurrent fetal loss.

PMID- 16634763
TI  - Exercise-induced fibrin formation is enhanced in women using third-generation
      oral contraceptives.

PMID- 16634764
TI  - Variation in coagulation inhibitors during prolonged sitting: possible
      pathogenetic mechanisms for travel-associated thrombosis.

PMID- 16634765
TI  - Physical stress as a model to study variations in ADAMTS-13 activity, von
      Willebrand factor level and platelet activation.

PMID- 16634766
TI  - Fibrinogen and prothrombin binding is enhanced to the Pro33 isoform of purified
      integrin alphaIIbbeta3.

PMID- 16634767
TI  - Comparison of the Villalta and Ginsberg clinical scales to diagnose the post
      thrombotic syndrome: correlation with patient-reported disease burden and venous
      valvular reflux.

PMID- 16634768
TI  - Severity of acute coronary syndrome is predicted by interactions between
      fibrinogen concentrations and polymorphisms in the GPIIIa and FXIII genes.

PMID- 16634769
TI  - P2Y1 gene A1622G dimorphism is not associated with adenosine diphosphate-induced
      platelet activation and aggregation after administration of a single high dose of
      clopidogrel.

PMID- 16634770
TI  - Can we prevent inhibitors in mild and moderate factor VIII-deficient patients?

PMID- 16634771
TI  - Identifying acutely ill medical patients requiring thromboprophylaxis.

PMID- 16634772
TI  - Risk of arterial thrombosis in carriers of familial thrombophilia.

PMID- 16634773
TI  - Alternatively spliced tissue factor in mice: induction by Streptococcus
      pneumoniae.

PMID- 16634774
TI  - Simple, rapid and automated method for detection of hyperaggregability of
      platelets in sleep apnea syndrome.

PMID- 16634775
TI  - Old and new risk factors for upper extremity deep venous thrombosis - a rebuttal.

PMID- 16634780
TI  - Gating of the expressed T-type Cav3.1 calcium channels is modulated by Ca2+.
AB  - AIM: We have investigated the influence of Ca2+ ions on the basic biophysical
      properties of T-type calcium channels. METHODS: The Cav3.1 calcium channel was
      transiently expressed in HEK 293 cells. Current was measured using the whole cell
      patch clamp technique. Ca2+ or Na+ ions were used as charge carriers. The
      intracellular Ca2+ was either decreased by the addition of 10 mm
      ethyleneglycoltetraacetic acid (EGTA) or increased by the addition of 200 microm
      Ca2+ into the non-buffered intracellular solution. Various combinations of extra-
      and intracellular solutions yielded high, intermediate or low intracellular Ca2+
      levels. RESULTS: The amplitude of the calcium current was independent of
      intracellular Ca2+ concentrations. High levels of intracellular Ca2+ accelerated
      significantly both the inactivation and the activation time constants of the
      current. The replacement of extracellular Ca2+ by Na+ as charge carrier did not
      affect the absolute value of the activation and inactivation time constants, but
      significantly enhanced the slope factor of the voltage dependence of the
      inactivation time constant. Slope factors of voltage dependencies of channel
      activation and inactivation were significantly enhanced. The recovery from
      inactivation was faster when Ca2+ was a charge carrier. The number of available
      channels saturated for membrane voltages more negative than -100 mV for the Ca2+
      current, but did not reach steady state even at -150 mV for the Na+ current.
      CONCLUSIONS: Ca2+ ions facilitate transitions of Cav3.1 channel from open into
      closed and inactivated states as well as backwards transition from inactivated
      into closed state, possibly by interacting with its voltage sensor.

PMID- 16634781
TI  - Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow
      during exercise.
AB  - AIM: The influence of exhaustive stretch-shortening cycle exercise (SSC) on
      skeletal muscle blood flow (BF) during exercise is currently unknown. METHODS:
      Quadriceps femoris (QF) BF was measured in eight healthy men using positron
      emission tomography before and 3 days after exhaustive SSC exercise. The SSC
      protocol consisted of maximal and submaximal drop jumps with one leg. Needle
      biopsies of the vastus lateralis muscles were taken immediately and 2 days after
      SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta
      (IL-1beta) mRNA level determinations. RESULTS: All subjects reported subjective
      muscle soreness after SSC (P < 0.001), which was well in line with a decrease in
      maximal isometric contraction force (MVC) and increase in serum creatine kinase
      activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P =
      0.043) and in its deep and superficial muscle regions, whereas oxygen uptake
      remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30
      min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or
      unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P =
      0.779) mRNA levels after SSC. CONCLUSION: It was concluded that fatiguing SSC
      exercise induces increased muscle BF during exercise, which is likely to be
      associated with pro-inflammatory processes in the exercised muscle.

PMID- 16634782
TI  - Na+ and pH dependence of proline and beta-alanine absorption in rat small
      intestine.
AB  - AIMS: Early characterization of intestinal absorption of imino acids in mammals
      has demonstrated the existence of a Na+-dependent, Cl- -independent transport
      system in rat small intestine, which is the only carrier for beta-alanine. Based
      on the substrate selectivity, it was proposed that the Proton Amino Acid
      Transporter 1 (PAT1) could be the same as this imino acid carrier. The present
      study characterizes the pH and Na+ dependence of proline and beta-alanine uptake
      in rat small intestine. METHODS: Intestinal uptake of radiolabelled l-proline or
      beta-alanine was measured in brush border membrane vesicles and everted
      intestinal rings, in the presence and absence of Na+ and at different pH values.
      RESULTS: The existence of an inwardly directed H+ gradient in the absence of Na+
      enhanced the initial entry of proline and beta-alanine in brush border membrane
      vesicles, that reached a transient overshoot with maximal value around 30 s. In
      the absence of pH gradient, no overshoot was shown. In entire tissue, there was
      an increase of proline and beta-alanine uptake at acidic pH that was higher in
      the presence of Na+ than in its absence. This ion dependence and pH effect of the
      amino acids uptake also increased with the incubation period. Substrate
      inhibition studies confirmed that intestinal proline absorption in rat occurs
      mainly by system B and PAT1-like transporter. CONCLUSIONS: There is a Na+ 
      independent, H+ -dependent transporter of amino acids at the apical membrane of
      the rat enterocytes.

PMID- 16634783
TI  - Products of cyclooxygenase-2 depress duodenal function in rats subjected to
      abdominal surgery.
AB  - AIM: Abdominal surgery evokes powerful biological responses that affect
      gastrointestinal functions. Here we investigate the role of the cyclooxygenase-1
      (COX-1) and cyclooxygenase-2 (COX-2) isoforms in post-operative duodenal ileus.
      METHODS: Proximal duodenum of anesthetized rats was perfused in situ with
      isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility,
      mucosal permeability and effluent osmolality were determined in the absence and
      presence of different COX inhibitors. RESULTS: The majority of control animals
      had no or few duodenal contractions and bicarbonate secretion averaged 10.9 +/-
      1.4 micromol cm(-1) h(-1). These 'paralytic' controls responded to hypotonic NaCl
      with a small increase in mucosal permeability. In control animals exhibiting
      spontaneous duodenal contractions, the bicarbonate secretion was 50% higher and
      the hypotonicity-induced net increase in mucosal permeability sevenfold higher
      than in 'paralytic' controls. Treatment with the selective COX-2 inhibitors
      rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion
      and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2
      inhibited animals had a twofold greater capacity to adjust luminal osmolality
      than 'paralytic' controls. The selective COX-1 inhibitor SC-560 only transiently
      stimulated motility and bicarbonate secretion and the hypotonicity-induced
      increase in mucosal permeability was smaller than in COX-2-inhibited animals.
      CONCLUSIONS: Abdominal surgery increases the synthesis of prostanoids,
      particularly via the COX-2 isoform. This compromises the ability of the duodenum
      to contract and to secrete HCO and to adjust luminal osmolality possibly via
      altered mucosal permeability. It is proposed that studies of gastrointestinal
      functions in animals subjected to abdominal surgery should include animals pre
      treated with a COX-2 inhibitor.

PMID- 16634784
TI  - The expression of IGF-I and myostatin mRNAs in skeletal muscle of
      hypophysectomized and underfed rats during postnatal growth.
AB  - AIM: To determine the roles of myostatin and insulin-like growth factor-I (IGF-I)
      during postnatal growth, we examined IGF-I and myostatin mRNA expression in the
      skeletal muscles of hypophysectomized and underfed rats during postnatal growth.
      METHODS: Five-week-old rats were divided into four groups: freely fed control,
      moderately underfed, severely underfed and hypophysectomized. Four weeks later,
      blood and muscle samples were gathered to determine serum IGF-I, myosin heavy
      chain (MHC) isoforms, IGF-I Ea, IGF-I Eb and myostatin mRNA. RESULTS: The weights
      of soleus, plantaris and masseter muscles were decreased in underfed and
      hypophysectomized rats. Hypophysectomy resulted in significant increases of type
      I MHC at the expense of type IIx in plantaris muscle and of neonatal MHC at the
      expense of types IIx and IIb in masseter muscle. Serum IGF-I was decreased by
      underfeeding and hypophysectomy. Plantaris muscle IGF-I Ea mRNA in underfed and
      hypophysectomized rats was significantly lower than in normal controls. Plantaris
      muscle IGF-I Eb mRNA in underfed rats was significantly lower than in normal
      controls. Masseter muscle IGF-I Eb mRNA in severely underfed rats was
      significantly lower than in normal control and hypophysectomized rats. Soleus
      muscle myostatin mRNA in hypophysectomized rats was significantly higher than in
      normal and significantly underfed rats. No significant differences in plantaris
      and masseter muscle myostatin mRNA were observed between groups. CONCLUSION:
      Suppressed muscle growth caused by hypophysectomy and underfeeding may be
      attributed mainly to reduced circulating IGF-I and partially to reduced IGF-I
      mRNA, rather than to a change in myostatin.

PMID- 16634785
TI  - Comparison of non-invasive measures of cholinergic and allergic airway
      responsiveness in rats.
AB  - AIM: Non-invasive analysis of tidal expiratory flow parameters such as Tme/TE
      (time needed to reach peak expiratory flow divided by total expiratory time) or
      midexpiratory tidal flow (EF50) has been shown useful for phenotypic
      characterization of lung function in humans and animal models. In this study, we
      aimed to compare the utility of two non-invasive measures, EF50 and Tme/TE, to
      monitor bronchoconstriction to inhaled cholinergic and allergic challenges in
      Brown-Norway rats. METHODS: Non-invasive measurements of Tme/TE and EF50 were
      paralleled by invasive recordings of Tme/TE, EF50 and pulmonary conductance (GL).
      RESULTS: First, dose-response studies with acetylcholine were performed in naive
      rats, showing that EF50 better than Tme/TE reflected the dose-related changes as
      observed with the classical invasive outcome parameter GL. The subsequent
      determination of allergen-specific early airway responsiveness (EAR) showed that
      ovalbumin-sensitized and -challenged rats exhibited airway inflammation and
      allergen-specific EAR. Again, EF50 was more sensitive than Tme/TE in detecting
      the allergen-specific EAR recorded with invasive and non-invasive lung function
      methods and agreed well with classical GL measurements. CONCLUSION: We conclude
      that non-invasive assessment of EF50 is significantly superior to Tme/TE and
      serves as a suitable and valid tool for phenotypic screening of cholinergic and
      allergic airway responsiveness in rats.

PMID- 16634786
TI  - Does central nitric oxide chronically modulate the acute hypoxic ventilatory
      response in conscious rats?
AB  - AIM: Hypoxia initiates an increase in ventilation (VE) through a cascade of
      events of which central nitric oxide (NO) has been implicated as an important
      neuromodulator. There have not been any reports describing the consequences of
      long-term imbalances in the central NO pathways on the modulation of the acute
      hypoxic ventilatory response (HVR). Chronic hypoxia (CH) can potentially modify
      the HVR, and so we hypothesized that central NO may be involved. In this study we
      describe the long-term role of central NO in the modulation of HVR before and
      after CH. METHODS: Male Sprague-Dawley rats (BW c. 200-320 g; n = 21) were
      implanted with an osmotic pump for continuous intracerebroventricular
      administration of either artificial cerebrospinal fluid (control), Nomega-nitro-L
      arginine methyl ester (L-NAME) (150 microg kg(-1) day(-1)) or the NO-donor, 3-[4
      morpholinyl]-sydnonimine-hydrochloride (SIN-1) (100 microg kg(-1) day(-1)). The
      VE response to acute poikilocapnic hypoxia (8% O2 for 20 min) was measured by
      plethysmography seven days after surgery, in normoxia, and again after 14 days of
      exposure to CH (CH = 12% O2). RESULTS: The magnitude of the HVR (c. 230% increase
      in VE) was unaltered by centrally infusing either L-NAME or SIN-1 for 1 week. CH
      did not modify the HVR, although baseline VE and HVR were shifted downward by L
      NAME during CH - because of a reduction in the frequency component. CONCLUSIONS:
      These results suggest that long-term alterations in central NO levels may not
      alter the HVR under moderate CH, presumably because of the onset/development of
      compensatory mechanisms. However, NO appears to be an important component of the
      HVR following CH.

PMID- 16634788
TI  - Convincing evidence for the pumping activity of lymphatics.

PMID- 16634789
TI  - Ischaemia is linked to inflammation and induction of angiogenesis in pancreatic
      islets.
AB  - Beta-cell replacement is the only way to restore euglycaemia in patients with
      type-1 diabetes. Pancreatic tissue, processed for subsequent clinical islet
      transplantation, is exposed to ischaemia causing injury and death in a large
      number of islets before and after transplantation. In this review we summarize
      what is known on the sources of environmental stress for pancreatic islets, such
      as insufficient oxygen supply during pancreas procurement and in culture prior to
      intraportal transplantation, nutritional and oxygen deprivation during the
      isolation process, and the consequences of hyperglycaemia. An increasingly
      recognized role in the modulation of beta-cell function and these environmental
      stress factors plays the vascular network of the pancreatic islets. Islet
      revascularization by angiogenesis is relevant for the survival of the graft
      subsequent to transplantation. Potential strategies offered by therapeutic
      induction of revascularization to ameliorate the detrimental impact of these
      factors on the quality of islet transplants are discussed.

PMID- 16634790
TI  - Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and
      reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal
      versus abnormal alanine aminotransferase levels.
AB  - CD4+CD25+ T regulatory cells may play a role in the different clinical
      presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T
      cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with
      normal and abnormal alanine aminotransferase (ALT) were analysed for specificity
      and effect on HCV-specific CD4+ T cell reactivity by flow cytometry for
      intracellular cytokine production and proliferation assay. HCV-specific
      CD4+CD25(+high) T cells consistently produced transforming growth factor (TGF)
      beta but only limited amounts of interleukin (IL)-10 and no IL-2 and interferon
      (IFN)-gamma. The HCV-specific TGF-beta response by CD4+CD25(+high) T cells was
      significantly greater in patients with normal ALT compared to patients with
      elevated ALT. In addition, a significant inverse correlation was found between
      the HCV-specific TGF-beta response by CD4+CD25(+high) T cells and liver
      inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen
      induced IFN-gamma production and proliferation of CD4+ T cells were greater in
      patients with elevated ALT compared with patients with normal ALT. Depletion of
      CD4+CD25+ cells from PBMC resulted in an increase of both IFN-gamma production
      and proliferation of HCV-specific CD4+ T cells that was significantly greater in
      patients with normal ALT levels compared with patients with elevated ALT. In
      addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be
      significantly more potent to suppress CD4+ T cell reactivity with respect to
      those from patients with elevated ALT. In conclusion, these data support the
      hypothesis that CD4+CD25+ cells may play a role in controlling chronic
      inflammatory response and hepatic damage in chronic HCV carriers.

PMID- 16634791
TI  - Immunohistochemical analysis of coeliac mucosa following ingestion of oats.
AB  - There is now considerable clinical evidence that oats do not activate coeliac
      disease. Nonetheless, a reluctance to include oats in the gluten-free diet
      remains. Because gluten-induced damage is accompanied by activation of the
      gastrointestinal immune system, the purpose of this study was to investigate if
      similar changes were induced by oats ingestion. Small intestinal histological
      sections from 10 patients who ingested 50 g of oats daily for 3 months were
      investigated for possible evidence of immune activation. Tissue obtained before
      and after oats challenge was stained with a series of antibodies directed against
      the following molecules: human leucocyte antigen D-related (HLA-DR), Ki-67, CD25,
      CD54 [intercellular adhesion molecule 1 (ICAM-1)] and mast cell tryptase. None of
      the patients developed clinical or laboratory evidence of adverse effects. The
      distribution of intestinal HLA-DR expression was not affected by oats ingestion
      and the crypt epithelium remained unstained. In the pre-oats biopsies, the
      percentage of Ki-67 positive enterocytes, 29.5 +/- 6.9 [95% confidence interval
      (CI) 13.9-45.0] did not differ significantly from that found in post-oats
      biopsies, 41.2 +/- 3.7 (95% CI, 32.8-49.6), P = 0.19, not significant.
      Furthermore, oats ingestion did not alter the number of CD25 positive and
      tryptase positive cells. Finally, the distribution and intensity of ICAM-1
      staining was unchanged by dietary oats. In summary, detailed immunohistological
      studies of biopsies from patients ingesting oats for 3 months did not reveal
      evidence of immune activation. Together with other reported findings, this study
      strengthens the view that oats can be included safely in the diet of gluten
      sensitive patients.

PMID- 16634792
TI  - Presence of IgE cells in human placenta is independent of malaria infection or
      chorioamnionitis.
AB  - We have shown previously that numerous IgE(+) macrophage-like cells are present
      in the villous stroma of full term placenta and that there was no difference in
      the amount of IgE(+) cells between allergic and non-allergic mothers. The
      presence of such an abundant number of IgE(+) cells in the placenta in allergic
      as well as non-allergic women suggests that the IgE is of some importance for a
      successful pregnancy outcome. Here we have investigated the IgE-pattern in 59
      placentas from second and third trimesters from Sweden with different degrees of
      chorioamnionitis and 27 full term placentas from Ghana with and without malaria
      parasites. The immunohistochemical staining pattern for IgE looked similar to our
      previous study, with the IgE located on Hofbauer-like cells. We could not find
      any difference in the amount or distribution of IgE(+) cells between malaria
      infected and non-infected placentas, nor between different degrees of
      chorioamnionitis. The IgE score in the placenta did not correlate with the levels
      of IgE in maternal serum or plasma. However, the IgE score was significantly
      higher in second- compared to third-trimester placentas (P = 0.03). This might
      reflect a maturation time-point in the fetus and in the intrauterine environment
      during the second trimester, or it might be associated with the increased number
      of intrauterine fetal deaths in the second trimester.

PMID- 16634793
TI  - Association of epithelial damage and signs of neutrophil mobilization in the
      airways during acute exacerbations of paediatric asthma.
AB  - We examined whether epithelial damage is associated with mobilization of
      neutrophils or eosinophils in the airway lumen during acute exacerbations of
      paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric
      patients (mean age 3.4 +/- 0.4 years) during acute exacerbations of asthma.
      Patients with signs of infection were excluded. The presence of conglomerates of
      epithelial cells (i.e. "Creola bodies") in the aspirated sputum was utilized as a
      marker of epithelial damage. Among the paediatric asthma patients, 60% displayed
      Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining
      patients did not (CrB-: n = 26). CrB+ patients displayed more than a 20-fold
      increase in the concentration of the neutrophil-mobilizing cytokine interleukin
      (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l),
      respectively, compared with CrB- patients (IL-8: 7468.2 +/- 1953.6 versus 347.9
      +/- 72.6, P < 0.01; NE: 2072.4 +/- 419.0 versus 438.5 +/- 125.7, P < 0.01). Even
      though not statistically significant, a corresponding trend was observed for the
      relative number of sputum neutrophils. In contrast, the concentration of the
      eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be
      lower in CrB+ than in CrB- patients (P > 0.05). In conclusion, as indicated by
      the analysis of aspirated sputum, epithelial damage is associated with a locally
      enhanced chemotactic signal for and activity of neutrophils, but not eosinophils,
      during acute exacerbations of paediatric asthma. It remains to be determined
      whether these indirect signs of neutrophil mobilization in the airway lumen
      mirror an increased number of neutrophils in the surrounding airway tissue.

PMID- 16634794
TI  - The presence of antibodies to oxidative modified proteins in serum from
      polycystic ovary syndrome patients.
AB  - Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age. Free
      radicals, as a product of oxidative stress, impair cells and tissue properties
      related to human fertility. These free radicals, together with the oxidized
      molecules, may have a cytotoxic or deleterious effects on sperm and oocytes, on
      early embryo development or on the endometrium. Aldehyde-modified proteins are
      highly immunogenic and circulating autoantibodies to new epitopes, such as
      malondialdehyde (MDA), may affect the reproductive system. Autoantibodies or
      elevated reactive oxygen species (ROS) in serum are often associated with
      inflammatory response. The purpose of this work is to investigate whether PCOS
      women show increased levels of oxidized proteins (protein-MDA) and anti
      endometrial antibodies (AEA) in their sera, compared with control patients, and
      to determine whether AEA specificity is related to oxidized protein derivatives.
      Sera from 31 women [10 patients with PCOS (PCOS group) and 21 women with male
      factor of infertility (control group)] were chosen from patients attending for
      infertility. Anti-endometrial antibodies were determined by enzyme-linked
      immunosorbent assay (ELISA) with an endometrial cell line (RL-95). Antibodies
      against MDA modified human serum albumin (HSA-MDA) were also determined by ELISA.
      Oxidized proteins (protein-MDA) in serum were determined by a colorimetric assay.
      Patients with PCOS have significantly higher levels of AEA and anti-HSA-MDA, as
      well as oxidized proteins (protein-MDA) in serum than control patients. For the
      first time, we describe an autoimmune response in PCOS patients, in terms of AEA.
      The evidence of protein-MDA in the serum of these patients, together with the
      increased antibody reactivity to MDA-modified proteins (HSA-MDA) in vitro,
      supports the conclusion that oxidative stress may be one of the important causes
      for abnormal endometrial environment with poor embryo receptivity in PCOS
      patients.

PMID- 16634795
TI  - The analysis and quantification of a clonal B cell response in a hyperimmunized
      anti-D donor.
AB  - Healthy volunteers are hyperimmunized with RhD-positive red cells in order to
      obtain plasma containing high titres of anti-D immunoglobulin, which is used for
      the prevention of haemolytic disease of the fetus and newborn. We analysed the
      anti-D immune response in a donor who had been hyperimmunized for 7 years and who
      showed declining anti-D titres despite re-immunization. A phage display library
      representing the complete immunorepertoire and a second library representing the
      IGHV3 superspecies family genes (IGHV3s) repertoire in the donor were constructed
      and analysed. A clonal Ig-gene rearrangement was quantified in the peripheral
      blood by limiting dilution polymerase chain reaction (PCR) All RhD-binding phages
      from both libraries, except one, had heavy chains with IGH-VDJ rearrangements of
      the same clonal origin, but with different patterns of somatic mutations and
      joined with different light chains. Limiting dilution PCR performed on mRNA and
      genomic DNA showed a frequency of 1 clonal B cell in 2000 IgG1/3-positive B
      cells. We show the presence of clonally related RhD-specific B cells in a
      hyperimmunized anti-D donor who had declining anti-D titres and who was
      unresponsive to re-immunization. Furthermore, we found a high frequency of clonal
      B cells. These results contribute to the understanding of the immune response
      against RhD in hyperimmunized anti-D donors.

PMID- 16634796
TI  - Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency
      disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and
      interferon-gamma gene.
AB  - Common variable immunodeficiency disease (CVID) is a heterogeneous syndrome
      characterized by low immunoglobulin serum levels and recurrent bacterial
      infections. Several studies suggest that CVID patients have a polarized immune
      response towards a T helper type 1 phenotype (TH1). However, the factors causing
      the TH1 polarization remain to be determined in this disease. In the present
      study, serum interleukin (IL)-12, interferon (IFN)-gamma levels and the IL-12p40
      and IFN-gamma gene were studied in CVID patients. Furthermore, we evaluate
      dendritic cells (DCs) compartment, myeloid dendritic cells (mDCs) and
      plasmocytoid dendritic cells (pDCs), which help to differentiate naive T cells
      preferentially into TH1 and TH2, respectively. The serum IL-12p40 subunit levels
      were increased significantly in CVID patients compared to healthy controls. We
      examined whether these elevated serum IL-12p40 levels are associated with IFN
      gamma or IL-12p40 gene polymorphisms, or with new mutations in the IL-12p40
      promoter gene. In our hands, no new mutations were found and gene polymorphisms
      frequencies in CVID patients were similar to the control population. In
      conclusion, the elevated serum levels of IL-12p40 found in our CVID patients were
      not related to these genetic variations. The DC compartment analysis did not show
      an imbalance between pDCs and mDCs, but revealed the presence of low numbers and
      percentage of both DC populations in CVID.

PMID- 16634797
TI  - Influence of major surgery on the mannan-binding lectin pathway of innate
      immunity.
AB  - The mannan-binding lectin (MBL) pathway of complement activation is important in
      host defence against pathogens and possibly against cancer. We investigated the
      effect of major surgery on two central components of the MBL pathway; MBL and the
      MBL-associated serine protease MASP-2, and for comparison also measured the
      interleukin (IL)-6 and C-reactive protein (CRP) levels. Serial blood samples were
      obtained from patients belonging to two different cohorts. Cohort 1 comprised 60
      patients undergoing open or laparoscopic colectomy for benign disease (n = 12) or
      colon cancer (n = 48). Cohort 2 comprised 27 patients undergoing elective, open
      surgery for colorectal cancer, and was included in order to cover blood sampling
      between days 2 and 6. As expected, the surgical stress induced a marked acute
      phase response, as evidenced by a large increase in IL-6 (18-fold) and CRP (13
      fold) levels with maximum at 12 h and 2 days, respectively. However, in both
      cohorts the levels of MBL and MBL-associated serine protease 2 (MASP-2) were
      largely unaffected, except for a minor but significant increase around day 8 in
      cohort 1. The preoperative levels of IL-6 and CRP were correlated significantly
      in both cohorts (r = 0.71, P < 0.0001 and r = 0.65, P = 0.005, respectively).
      Preoperative MASP-2 correlated with preoperative CRP (r = 0.59, P = 0.001) and IL
      6 (r = 0.55, P = 0.02) in cohort 2 only. In contrast to the marked effects on the
      levels of IL-6 and CRP, the surgery influenced only marginally the two proteins
      of the MBL pathway.

PMID- 16634798
TI  - Circulating IgA from acute stage of childhood Henoch-Schonlein purpura can
      enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling
      pathway.
AB  - Recently, sera from children with active Henoch-Schonlein purpura (HSP) have been
      found to enhance interleukin (IL)-8 production by human umbilical venous
      endothelial cells (HUVEC). To further determine the possible factor with the
      ability to enhance endothelial IL-8 production in sera from acute stage of HSP,
      10 children with HSP at the acute stage and 10 healthy controls were enrolled.
      IgA antiendothelial cell antibodies (AECA) were detected by cell-based ELISA.
      Active sera with or without pretreatment with anti-human IgA antibody, sera of
      controls, and immunoglobulin A (IgA) derived from sera were used to stimulate the
      HUVEC. The ability of these factors to enhance endothelial IL-8 production was
      evaluated. Furthermore, signalling pathways were also assayed by different
      inhibitors, and confirmed by immunoblotting. Serum levels of IgA AECA in HPS
      patients at the acute stage were significantly higher than in controls (P <
      0.001). The active sera could enhance endothelial IL-8 production (P = 0.004,
      compared with control sera), and the ability of these sera was mostly abolished
      when pretreated with fixed anti-human IgA antibody. The supernatant IL-8 levels
      of endothelial cells stimulated by IgA derived from acute stage of HSP were
      statistically higher than controls (P < 0.001). PD98059, an inhibitor of ERK
      phosphorylation, significantly reduced IgA AECA-stimulated endothelial IL-8. IgA
      AECA also enhanced the phosphorylation of ERK1 with a time-dependent manner.
      Together with these findings, it is concluded that IgA AECA derived from acute
      stage of HSP may bind to endothelial and enhance endothelial cells to produce IL
      8 via MEK/REK signalling pathway.

PMID- 16634799
TI  - Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces
      protective immune response in mice.
AB  - For most bacteria, adherence to human cells is achieved by bacterial lectins
      binding to mammalian surface glyconjugates. 6-Phosphogluconate dehydrogenase
      (6PGD) was identified by us as one of Streptococcus pneumoniae cell wall lectin
      proteins, which elicits an age-dependent immune response in humans. This study
      assesses the role of 6PGD in S. pneumoniae pathogenesis as an adhesin and its
      ability to elicit a protective immune response in mice. Recombinant 6PGD (r6PGD)
      was cloned from S. pneumoniae serotype 3 (strain WU2). r6PGD interference in
      adhesion of three genetically unrelated unencapsulated pneumococcal strains (3.8,
      14.8 and R6) and two genetically unrelated encapsulated pneumococcal strains (WU2
      and D39) to A549 type II lung carcinoma cell was tested. BALB/c mice were
      immunized with r6PGD and boosted after 3 weeks. Immunized mice were challenged
      intranasally with a lethal dose of S. pneumoniae. r6PGD inhibited 90% and 80% of
      pneumococcal adhesion to the A549 cells of three unencapsulated S. pneumoniae
      strains and two encapsulated S. pneumoniae strains, respectively, in a
      concentration-dependent manner (P < 0.05). Antibodies to r6PGD produced in mice
      significantly inhibited bacterial adhesion to A549 cell (P < 0.05). Immunization
      of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P <
      0.05) of the mice for 21 days following intranasal lethal challenge. We have
      identified 6PGD as a surface-located immunogenic lectin protein capable of acting
      as an adhesin. 6PGD importance to bacterial pathogenesis was demonstrated by the
      ability of r6PGD to elicit a protective immune response in mice.

PMID- 16634800
TI  - A combination of a transforming growth factor-beta antagonist and an inhibitor of
      cyclooxygenase is an effective treatment for murine pulmonary tuberculosis.
AB  - Transforming growth factor-beta (TGF-beta) and prostaglandins (PG) regulate the
      cell-mediated immune response, so it has been proposed that they affect the
      progression of pulmonary tuberculosis. Here we report that the administration of
      soluble betaglycan, a potent TGF-beta antagonist, and niflumic acid, a PG
      synthesis inhibitor, during the chronic phase of experimental murine tuberculosis
      enhanced Th1 and decreased Th2 cytokines, increased the expression of iNOS and
      reduced pulmonary inflammation, fibrosis and bacillary load. This
      immunotherapeutic approach resulted in significant control of the disease
      comparable to that achieved by anti-microbial treatment alone. Importantly, the
      combination of immunotherapy and anti-microbials resulted in an accelerated
      clearance of bacilli from the lung. These results confirm that TGF-beta and PG
      have a central pathophysiological role in the progression of pulmonary
      tuberculosis in the mouse and suggest that the addition of immunotherapy to
      conventional anti-microbial drugs might result in improved treatment of the
      disease.

PMID- 16634801
TI  - Role of interleukin (IL-10) in probiotic-mediated immune modulation: an
      assessment in wild-type and IL-10 knock-out mice.
AB  - While the impact of Bifidobacterium infantis 35624 and other probiotics on
      cytokines has been shown in established colitis, the effects of B. infantis
      consumption in pre-inflammation of interleukin (IL)-10 knock-out (KO) mice and on
      the wild-type (WT) C57Bl/6 mice have not been well demonstrated. The objective of
      this study was to examine cytokine responses in mucosal and systemic lymphoid
      compartments of IL-10 KO mice early in disease and to compare with control WT
      mice. Mice were fed B. infantis or placebo for 5 weeks and culled prior to the
      onset of chronic intestinal inflammation (12-14 weeks). The spleen, Peyer's
      patches and intestinal mucosa were removed and stimulated with various bacterial
      stimuli. Cytokine levels were measured by enzyme-linked immunosorbent assay.
      While basal intestinal and systemic cytokine profiles of WT and IL-10 KO mice
      were similar, transforming growth factor (TGF)-beta was reduced in the spleen of
      IL-10 KO mice. Following probiotic consumption, interferon (IFN)-gamma was
      reduced in the Peyer's patch of both WT and IL-10 KO mice. Alterations in IFN
      gamma in the Peyer's patches of WT mice (enhancement) versus IL-10 KO (reduction)
      were observed following in vitro stimulation with salmonella. Differential IL
      12p40, CCL2 and CCL5 responses were also observed in IL-10 KO mice and WT mice.
      The cytokine profile of IL-10 KO mice in early disease was similar to that of WT
      mice. The most pronounced changes occurred in the Peyer's patch of IL-10 KO mice,
      suggesting a probiotic mechanism of action independent of IL-10. This study
      provides a rationale for the use of B. infantis 35624 for the treatment of
      gastrointestinal inflammation.

PMID- 16634802
TI  - Cytokine expression profiles of bovine lymph nodes: effects of Mycobacterium
      bovis infection and bacille Calmette-Guerin vaccination.
AB  - Cytokine expression in lymph nodes from cattle inoculated intranasally with
      Mycobacterium bovis was compared to that of non-infected animals using real-time
      polymerase chain reaction. The effect of M. bovis infection, 4 months post
      challenge, was to suppress the expression of anti-inflammatory cytokines
      interleukin (IL)-4 and IL-10 as well as the pro-inflammatory cytokines tumour
      necrosis factor (TNF) and IL-6. Expression of interferon (IFN)-gamma and IL-12
      was maintained. Animals vaccinated with bacille Calmette-Guerin responded
      differently to challenge with M. bovis. In particular, no decrease in expression
      of IL-4 or IL-6 was observed following challenge of vaccinated animals and
      decreased IFN-gamma was detected. Also, vaccinated animals had higher levels of
      IL-4 and IL-10 transcripts compared to unvaccinated animals following challenge.
      These changes in cytokine expression levels led to a significant shift in the IFN
      gamma/IL-4 or IFN-gamma/IL-10 ratio within the lymph node following challenge.
      Challenged animals generally showed a strong Th1 bias that was not seen in
      animals vaccinated prior to challenge. An inverse correlation between the level
      of pathology and bacterial load within the lymph node and the expression of IL-4,
      IL-10 and TNF was also observed. These results suggest that in the lymph nodes of
      cattle with established tuberculosis and a persisting bacterial infection,
      maintenance of the pro-inflammatory response in combination with a suppressed
      anti-inflammatory response may control the infection but contribute to host
      induced tissue damage. Vaccination, which reduces the bacterial load and
      consequently the IFN-gamma response, may result in less suppression of anti
      inflammatory cytokines.

PMID- 16634803
TI  - Modulation of immune responses and suppression of experimental autoimmune
      myasthenia gravis by surgical denervation of the spleen.
AB  - Critical interactions between the nervous system and the immune system during
      experimental autoimmune myasthenia gravis (EAMG) were examined in an animal model
      for human MG after immunization of adult female Lewis rats with Torpedo
      acetylcholine receptor (AChR) and complete Freund's adjuvant. Immunized rats
      depicted marked clinical severity of the disease. Using enzyme-linked immunospot
      (ELISPOT) assay and in situ hybridization techniques, immune responses in these
      animals were examined and showed elevated numbers of anti-AChR IgG secreting B
      cells and AChR reactive interferon (IFN)-gamma-secreting cells, enhanced mRNA
      expression of the proinflammatory cytokines IFN-gamma and tumour necrosis factor
      (TNF)-alpha as Th1 subset and the anti-inflammatory cytokines interleukin (IL)-4
      and IL-10 as a Th2 subset, and transforming growth factor (TGF)-beta as a Th3
      cytokine. Corticosterone and prostaglandin E(2) (PGE(2)) levels were measured by
      radioimmunoassay and illustrated increased production after immunization.
      Surgical denervation of the spleen reduced significantly the clinical severity of
      the disease, suppressed the numbers of IgG and IFN-gamma-secreting cells, down
      regulated the mRNA expression for cytokines and reduced corticosterone and PGE(2)
      production. As controls, sham-operated rats were used and showed results as the
      EAMG non-denervated control rats. The data present herein, and for the first
      time, substantial effects of the nervous system on immune responses that may
      influence the outcome of EAMG. These effects were not dependent on cytokine
      inhibitory mediators such as prostaglandins or stress hormones. IL-10 and TGF
      beta, the two potent immunosuppressive cytokines, were also suppressed,
      indicating a general suppression by splenic denervation. More investigations are
      initiated at our laboratories to understand the evident neural control over the
      immune system during challenges leading to the break of tolerance and development
      of autoimmunity, which may assist in innovative therapeutic approaches.

PMID- 16634804
TI  - Cerebral leucocyte infiltration in lupus-prone MRL/MpJ-fas lpr mice--roles of
      intercellular adhesion molecule-1 and P-selectin.
AB  - The autoimmune disease which affects MRL/MpJ-fas(lpr) mice results in cerebral
      leucocyte recruitment and cognitive dysfunction. We have previously observed
      increased leucocyte trafficking in the cerebral microcirculation of these mice;
      however, the types of leucocytes recruited have not been analysed thoroughly, and
      the roles of key endothelial adhesion molecules in recruitment of these
      leucocytes have not been investigated. Therefore the aim of this study was to
      classify the phenotypes of leucocytes present in inflamed brains of MRL/MpJ
      fas(lpr) mice, and dissect the roles of endothelial adhesion molecules in their
      accumulation in the brain. Immunohistochemical analysis revealed significant
      leucocyte infiltration in the brains of 16- and 20-week-old MRL/MpJ-fas(lpr)
      mice, affecting predominantly the choroid plexus. Isolation of brain-infiltrating
      leucocytes revealed that lymphocytes and neutrophils were the main populations
      present. The CD3(+) lymphocytes in the brain consisted of similar proportions of
      CD4(+), CD8(+) and CD4(-)/CD8(-)[double negative (DN)] populations. Assessment of
      MRL/MpJ-fas(lpr) mice deficient in endothelial adhesion molecules intercellular
      adhesion molecule-1 (ICAM-1) or P-selectin indicated that cerebral leucocyte
      recruitment persisted in the absence of these molecules, with only minor changes
      in the phenotypes of infiltrating cells. Together these data indicate that the
      brains of MRL/MpJ-fas(lpr) mice are affected by a mixed leucocyte infiltrate, of
      which the unusual DN lymphocyte phenotype contributes a substantial proportion.
      In addition, endothelial adhesion molecules ICAM-1 and P-selectin, which modulate
      survival of MRL/MpJ-fas(lpr) mice, do not markedly inhibit leucocyte entry into
      the central nervous system.

PMID- 16634805
TI  - The role of Fc-receptors in murine mercury-induced systemic autoimmunity.
AB  - Inorganic mercury (Hg) in genetically susceptible mouse strains induces a T cell
      dependent, systemic autoimmune condition (HgIA) characterized by
      immunostimulation, anti-nuclear antibodies (ANA) and systemic immune-complex (IC)
      deposits. The exact phenotypic expression of HgIA in different strains depends on
      H-2 and non-H-2 genes. Fc receptors (FcRs) are important in the development of
      many autoimmune diseases. In this study, the effect of targeted mutations for
      activating and inhibiting FcRs in the BALB/c model of HgIA was examined. Hg
      treated BALB/c mice without mutation (wild-type, wt) showed heavy IC deposits in
      the renal glomerular mesangium, as well as in renal and splenic vessel walls. The
      renal mesangial IC deposits were severely reduced in Hg-treated BALB/c mice
      without the gamma-chain (lack of the activating receptors FcgammaRI, FcgammaRIII
      and FcinRI), but unchanged in mice lacking the inhibitory FcgammaRIIB. The Hg
      induced vessel wall IC deposits present in wt mice were abolished and reduced in
      the FcRgamma and FcgammaRIIB strains, respectively. Hg-treated BALB/c wt mice and
      mice without the gamma-chain showed an increase in serum IgE, while the increase
      in IgG1 was attenuated in the latter strain. In contrast, absence of the
      inhibiting FcgammaRIIB augmented the Hg-induced increase of both serum IgG1 and
      IgE. In conclusion, FcRs are important mainly for the induction of systmeic IC
      deposits in the HgIA model, but also affects serum IgG1 and IgE levels.

PMID- 16634806
TI  - Enhanced immunogenicity and antitumour effects with heterologous prime-boost
      regime using vaccines based on MG7-Ag mimotope of gastric cancer.
AB  - MG7-Ag, gastric cancer-associated antigen, has been shown to be immunogenic and
      has been used as marker molecule for prognosis. In a previous study, we developed
      an oral DNA vaccine based on MG7-Ag mimotope. However, we failed to detect
      cellular immune response using the oral MG7-Ag mimotope DNA vaccine. To induce
      significant T cell response, we developed a recombinant adenovirus vaccine based
      on MG7-Ag mimotope and evaluated the efficacy and protective effects of
      heterologous prime-boost immunization protocol with an oral DNA vaccine
      previously developed. We found that both vaccines were able to elicit a
      significant humoral response against MG7-Ag, while the highest serum titre MG7
      antibody was detected in mice immunized with the heterologous prime-boost
      immunization protocol. Enzyme-linked immunospot (ELISPOT) assay demonstrated that
      the heterologous prime-boost immunization strategy was more efficient in inducing
      T cell response than the homologous prime-boost strategy. In the tumour challenge
      assay, 2 of 5 mice immunized with the heterologous prime-boost protocol were
      tumour free, while none of the mice in homologous prime-boost groups or control
      groups was tumour free. Those tumour-bearing mice in the heterologous prime-boost
      regime had smaller tumour masses than their counterparts in the homologous prime
      boost groups or control groups. Therefore, our study suggests that vaccines
      against MG7-Ag induce significant immune response against gastric cancer, and
      that the heterologous prime-boost protocol using different types of vaccines
      could achieve better protective effect than the homologous prime-boost protocol.

PMID- 16634807
TI  - Sublytic complement C5b-9 complexes induce thrombospondin-1 production in rat
      glomerular mesangial cells via PI3-k/Akt: association with activation of latent
      transforming growth factor-beta1.
AB  - Mesangial cell proliferation is a common cellular response to a variety of
      different types of glomerular injury. Complement C5b-9 is a prime candidate to
      mediate mesangial cell proliferation, especially sublytic C5b-9, which can induce
      the production of multiple inflammatory factors and cytokines. Transforming
      growth factor (TGF)-beta1 plays a major role in the accumulation of extracellular
      matrix (ECM), while thrombospondin (TSP)-1 has been identified as an activator of
      latent TGF-beta1 in an in vitro system. Using rat glomerular mesangial cells
      (GMCs) as a model system, we assessed the effect of sublytic C5b-9 on the
      expression of TSP-1 and TGF-beta1 and explored the relevant pathway of signal
      transduction. First, we ensured the concentrations of anti-Thy1 antibody and
      complement, which were regarded as a sublytic C5b-9 dose, and examined whether
      the sublytic C5b-9 induced expression of TSP-1 in rat GMCs which, in turn,
      activated latent TGF-beta1 by real-time polymerase chain reaction (PCR) and
      enzyme-linked immunosorbent assay (ELISA), respectively. Then, we investigated
      the role of the PI3-k/Akt pathway in sublytic C5b-9-induced TSP-1 production in
      rat GMCs by Western blot analysis. The addition of sublytic C5b-9 (5% anti-Thy1
      antibody and 4% normal serum) to rat GMCs induced activation of latent TGF-beta1
      via TSP-1. The addition of sublytic C5b-9 apparently increased the protein of Akt
      phosphorylation, whereas PI3-k inhibitor LY294002 could clearly reduce the
      increase of TSP-1 induced by sublytic C5b-9. These results indicate that TSP-1 is
      an activator of latent TGF-beta1 in sublytic C5b-9-induced rat GMCs; furthermore,
      the PI3-k/Akt signal transduction pathway may play a key role in sublytic C5b-9
      induced TSP-1 production.

PMID- 16634808
TI  - Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like
      cells and phosphorylation of Gab adapter proteins activated by platelet-derived
      growth factor.
AB  - Receptors for platelet-derived growth factor (PDGF) are abundantly expressed on
      synovial fibroblast-like (SFL) cells from patients with rheumatoid arthritis
      (RA), and stimulation with PDGF enhances both the anchorage-dependent and 
      independent growth of RA-SFL cells. To elucidate the molecular mechanisms
      responsible for the excessive growth of RA-SFL cells and to seek a novel
      molecular-targeting therapy for RA, we examined the expression of adapter
      proteins and the effect of the specific inhibition of PDGF receptor activation by
      imatinib mesylate. Cultured SFL cells were used in the present study after 2-5
      passages. The anchorage-dependent and -independent growth patterns of the SFL
      cells were evaluated using a tetrazolium-based assay and colony formation in 0.3%
      agar, respectively. Adapter proteins Gab1 and Gab2 were expressed in RA-SFL
      cells, and both proteins were rapidly (< 1 min) tyrosine-phosphorylated after the
      stimulation of RA-SFL cells with 10 ng/ml of PDGF and, to a lesser extent, after
      stimulation with 100 ng/ml of epidermal growth factor (EGF). The inhibition of
      PDGF receptor tyrosine kinase activation by 1 microM or less of imatinib mesylate
      specifically suppressed the PDGF-dependent, but not EGF-dependent, tyrosine
      phosphorylation of various proteins. Moreover, imatinib mesylate abolished both
      the anchorage-dependent and -independent proliferation of RA-SFL cells induced by
      PDGF stimulation. These results suggest that Gab adapter proteins are expressed
      and likely to be involved in the growth signalling of rheumatoid synovial cells
      and that imatinib mesylate, a key drug in the treatment of chronic myeloid
      leukaemia, may also be effective for the treatment of RA.

PMID- 16634809
TI  - The C-terminus of complement regulator Factor H mediates target recognition:
      evidence for a compact conformation of the native protein.
AB  - The complement inhibitor Factor H has three distinct binding sites for C3b and
      for heparin, but in solution uses specifically the most C-terminal domain, i.e.
      short consensus repeats (SCR) 20 for ligand interaction. Two novel monoclonal
      antibodies (mABs C14 and C18) that bind to the most C-terminal domain SCR 20
      completely blocked interaction of Factor H with the ligands C3b, C3d, heparin and
      binding to endothelial cells. In contrast, several mAbs that bind to the N
      terminus and to the middle regions of the molecule showed no or minor inhibitory
      effects when assayed by enzyme-linked immunosorbent assay (ELISA) and ligand
      interaction assays. This paradox between a single functional binding site
      identified for native Factor H versus multiple interaction sites reported for
      deletion constructs is explained by a compact conformation of the fluid phase
      protein with one accessible binding site. On zymosan particles mAbs C14 and C18
      blocked alternative pathway activation completely. Thus demonstrating that native
      Factor H makes the first and initial contact with the C terminus, which is
      followed by N terminally mediated complement regulation. These results are
      explained by a conformational hypothetical model: the native Factor H protein has
      a compact structure and only one binding site accessible. Upon the first contact
      the protein unfolds and exposes the additional binding sites. This model does
      explain how Factor H mediates recognition functions during complement control and
      the clustering of disease associated mutations in patients with haemolytic
      uraemic syndrome that have been reported in the C-terminal recognition domain of
      Factor H.

PMID- 16634810
TI  - PDGF receptor tyrosine kinase inhibitor suppresses mesangial cell proliferation
      involving STAT3 activation.
AB  - Proliferation of mesangial cells is a hallmark of glomerular disease, and
      understanding the regulatory mechanisms is critically important. The purpose of
      this study was to examine the relationship between mesangial cell proliferation
      and phosphorylated signal transducer and activator of transcription (STAT) 3 and
      to determine whether the PDGF receptor tyrosine kinase inhibitor STI 571
      inhibited mesangial cell proliferation via modulation of STAT3. In this study, we
      investigated for the first time, the glomerular expression of phosphorylated
      STAT3 in paraffin sections from animals with experimental mesangial proliferative
      glomeronephritis. Phosphorylated STAT3 colocalized with many proliferating
      mesangial cells. We also demonstrated that treatment with STI 571 reduced
      mesangial cell proliferation and phosphorylated STAT3 signalling both in vitro
      and in vivo. In vivo, STI 571 treatment reduced the number of glomerular
      mesangial cells positive for both phosphorylated STAT3 and proliferating cell
      nuclear antigen. In summary, phosphorylated STAT3 is strongly expressed during
      mesangial cell proliferation and STI 571 induced suppression of mesangial cell
      proliferation involves inhibition of phosphorylated STAT3 signalling.

PMID- 16634811
TI  - Modulation of endothelial monolayer permeability induced by plasma obtained from
      lipopolysaccharide-stimulated whole blood.
AB  - The aim of this study was to elucidate the time course of the permeability
      response of endothelial monolayers after exposure to plasma obtained from
      lipopolysaccharide (LPS)-treated human whole blood; to investigate the role of
      apoptosis in monolayer permeability, and to inhibit the permeability increase,
      particularly after addition of the plasma stimulus. Human umbilical vein
      endothelial cells (HUVEC) were cultured on semiporous membranes and the
      permeability for albumin was measured after exposure, according to different
      schedules, to LPS-conditioned plasma. Apoptotic HUVEC were measured by both flow
      cytometry and ELISA. A variety of agents, including antibodies against cytokines,
      inhibitors of NF-kappaB, and a caspase inhibitor, were added to HUVEC, either
      prior to or after the stimulus. A maximum increase of the permeability was
      achieved after 4-6 h of exposure to LPS-conditioned plasma. This response was not
      accompanied by an increase in the number of apoptotic HUVEC. Administration of
      antibodies against both Tumour Necrosis Factor-alpha (TNF-alpha) and Interleukin
      1beta (IL-1beta) to HUVEC within 1 h after stimulation significantly reduced the
      permeability increase. Similarly, pyrollidine di-thiocarbamate (PDTC), but not N
      acetylcysteine, could prevent the permeability response, and was still effective
      when added within 2 h after LPS-conditioned plasma. The TNF-alpha/IL-1beta signal
      present in LPS-conditioned plasma appears to increase endothelial permeability
      through intracellular pathways that very likely involve the activation of NF
      kappaB. Although poststimulatory inhibition of the permeability response proves
      to be possible with agents such as PDTC, the window of opportunity appears very
      small if placed in a clinical perspective.

PMID- 16634812
TI  - Contents of stomatological curricula in Europe.
AB  - The present study focuses on dental education in the Accession Countries to the
      European Union. Comparisons were made with data from EU dental schools [Eur J
      Dent Educ 1 (1997) 35]. The findings show a large variation in the hours
      allocated to individual subjects, medical and dental, both within and between AC
      and EU dental schools. Stomatology derived from General Medicine and the
      stomatologist is viewed as a doctor responsible for one part of the body. This
      was explained by the large proportion of time dedicated to medical subjects,
      especially in the first 2/3 years of the undergraduate curriculum. The percentage
      of hours for dental sciences varied inversely to those for bio-medical sciences
      and increase continuously from the first year to the final year. Curricula in the
      Stomatological schools tend to have a discipline-structured approach, generally
      utilising a large number of individual departments, resulting in a multitude of
      subjects being taught. Curricular extensions from 5 to 6 years were introduced in
      some schools from 1990 onwards in order to accommodate new dental subjects.

PMID- 16634813
TI  - Quality of root canal fillings performed by undergraduate dental students on
      single-rooted teeth.
AB  - INTRODUCTION: Root canal therapy is an accepted and successful form of tooth
      conservation. Educational guidelines require dental schools to ensure that their
      graduates are competent on graduation at performing root canal therapy. The aim
      of this investigation was to assess the technical quality of root canal fillings
      placed by undergraduate students in single-rooted teeth. MATERIALS AND METHODS: A
      total of 100 radiographs of root canal fillings placed by undergraduate students
      in single-rooted teeth were examined under even illumination in a darkened room
      using x2 magnification. These were graded as 'adequate', where the root canal
      filling was within 2 mm of the radiographic apex, 'under-filled', where the root
      canal filling was >2 mm from the radiographic apex, and 'over-filled', where the
      root canal filling was extruded beyond the radiographic apex. The presence of
      voids, fractured instruments, and root perforations were also noted. RESULTS: All
      teeth were obturated with gutta-percha and sealer (Roth Cement), using a cold
      lateral condensation technique. Of 100 teeth, 10% (n = 10) had voids. Of the
      remainder, 70% (n = 63) were judged to be 'acceptable', 21% (n = 19) were 'under
      filled', and 9% (n = 8) were 'over-filled'. There was no evidence of fractured
      instruments or root perforations in any root filling examined. CONCLUSIONS: The
      quality of root canal fillings placed in single-rooted teeth by undergraduate
      dental students at the University Dental School and Hospital, Cork was acceptable
      (63% of root fillings placed in single rooted teeth were graded as 'adequate').
      The probable reasons for this are multi-factorial, but may be linked to the
      amount of pre-clinical and clinical teaching in endodontics at the University
      Dental School and Hospital, Cork. It should be remembered that factors other than
      radiographic quality/evidence must be considered when determining the outcome of
      root canal therapy.

PMID- 16634814
TI  - Dental school admissions in Ireland: can current selection criteria predict
      success?
AB  - INTRODUCTION: Entry into university education in Ireland, including dental
      school, is based solely on academic performance in the Leaving Certificate
      Examination, held at the end of formal school education. The aim of this
      investigation was to examine the suitability of this process for the selection of
      dental students in Ireland. MATERIALS AND METHODS: Information for all dental
      students who entered the dental degree programme immediately following completion
      of the Leaving Certificate Examination at the National University of Ireland,
      Cork, during the years 1997-1999 was retrieved. Information was collected
      relating to gender, the number of times the student had attempted the Leaving
      Certificate Examination, their performance in this examination, the total number
      of marks awarded to each student at the end of the First and Final Dental
      Examinations, and their performance in individual modules. RESULTS: Whilst there
      was a significant relationship between performance in the Leaving Certificate
      Examination and the First Dental Examination (correlation coefficient = 0.22, P <
      0.05), this relationship could only explain 12% of the variation within the
      performance of students in this examination. There was no relationship between
      performance in the Leaving Certificate and the Final Dental Examination
      (correlation coefficient = 0.09, P > 0.05). There was a significant correlation
      between performance in the Leaving Certificate Examination and performance in
      seven of the 55 programme modules, all of which were pre-clinical modules, and of
      which five were related to basic sciences. CONCLUSIONS: Based on the limitations
      of this study, the current selection process for dental students in Ireland seems
      to be of limited value.

PMID- 16634815
TI  - Student perspectives on their recent dental outreach placement experiences.
AB  - BACKGROUND: Dental schools are developing new curricula, with outreach placements
      enhancing the hospital-based training. OBJECTIVES: To assess the students'
      experience of outreach as one component of determining the value and feasibility
      of outreach placements. INTERVENTION: Six-week block placements for 10
      undergraduates and 3 weeks for 11 hygiene and hygiene and therapy students in
      existing primary care clinics, in areas of need, to work supervised by local
      dentists. METHODS: Semi-structured interviews with 20 students by staff
      independent of the course team. Interviews were audio-recorded, transcribed and
      content analysed before being verified by a second observer. Findings were
      triangulated against a peer-run focus group and students' clinical records.
      RESULTS: Students were very positive about their experience and the potential
      role of outreach training in dental education. They described: gaining greater
      experience of new types of patients and their communities; learning from broader
      clinical experience, alternative approaches and practicing or observing dentistry
      in different settings; the benefits of team working; and, acquiring a more
      holistic and pragmatic view of health care. Many students reported gaining
      greater confidence, wider awareness of potential careers in dentistry and a
      greater sense of realism in their experience. Some reflected on their own
      training needs. Students also discussed the importance of preparation for the
      placements and the merits of different styles of supervision. CONCLUSION: Dental
      outreach training can provide students with valuable learning experience in a
      range of areas. It requires careful management to ensure those experiences match
      individuals' needs and the programme's purposes.

PMID- 16634816
TI  - German dental faculty attitudes towards computer-assisted simulation systems
      correlated with personal and professional profiles.
AB  - BACKGROUND: Computer technology is increasingly used in practical training at
      universities. However, in spite of their potential, computer-assisted simulation
      (CAS) systems still appear to be underutilised. OBJECTIVES: To investigate the
      practical usage of CAS/computer-assisted learning (CAL) systems, the familiarity
      and level of use of CAS systems, as well as the acceptance of approved learning
      content and English as the language of instruction in CAS/CAL systems. METHODS: A
      survey was conducted in the Departments of Conservative Dentistry and Prosthetic
      Dentistry of all 32 dental schools in Germany. Besides investigating the
      usefulness of, familiarity with and level of current usage of CAS systems, the
      questionnaire also contained questions regarding each respondent's gender, age,
      academic rank, experience in academia and computer skills, all of which
      correlated with the responses. RESULTS: The response rate was 90% (112 out of
      125). The use of CAS/CAL systems was considered 'partly' to 'very' useful for
      evaluating the acquisition of knowledge (83.9%), qualitative issues (73.2%) and
      processes (72.3%) of dental preparation exercises and complex treatment
      strategies. However, only about half the respondents reported that they knew of,
      and even fewer used, the following systems in preclinical or clinical training:
      EDUnet (KaVo, Germany) (46.3%/0.9 %), PREPassistant (KaVo, Germany) (50%/0.9%),
      or the DentSim system (DenX, Israel) (52.8%/1.9%). The virtual simulation system
      VRDTS-CP (Novint, USA), used by none of the respondents, was known to only 16.5%.
      Responders agreed at least partly to accept approved learning content (74.9%) and
      English as the language of instruction (82.1%) as the standards for CAS systems.
      CONCLUSION: The survey indicates a distinct discrepancy between a generally
      positive attitude towards the usefulness of computer technology for dental
      education, the level of familiarity with current computer systems and their
      actual use. However, two prerequisites for ultimately decreasing the cost and
      increasing the usage of CAS systems--the acceptance of approved learning content
      and English as the language of instruction in CAS systems--seem to be generally
      accepted by respondents.

PMID- 16634817
TI  - Student evaluation of a problem-oriented module of clinical medicine within a
      revised dental curriculum.
AB  - As part of a revised dental curriculum, a 3(rd) year module on medical subjects
      was developed based on a mixture of self-study and problem-oriented approach
      using cases. Pairs of students had to select a specific medical problem and solve
      a paper patient case using a problem-solving cycle. Results were presented in
      working groups and by writing an essay. The quality of the presentations was
      assessed by colleague students and by the teacher supervisor; the expert teacher
      in the field graded the essay. The results contributed for 40% to the overall
      grade of the module. A questionnaire filled out by 94% of the participating
      students showed that 85% of the students agreed in preferring this way of
      handling medical problems as compared with conventional, lecture-based education.
      Almost all of them enjoyed the provided opportunity to give a case presentation.
      The problem-oriented model was assessed as useful by 73% of the students.
      Knowledge concerning the topic chosen turned out to be higher than knowledge of
      other topics. Although this study cannot prove that this mode of education
      actually results in a better ability to cope with medical problems, it may
      contribute in several ways to the final competences in the area of general
      medicine in the undergraduate dental curriculum.

PMID- 16634832
TI  - Emerging role of epoxyeicosatrienoic acids in coronary vascular function.
AB  - The importance of endothelium-derived nitric oxide in coronary vascular
      regulation is well-established and the loss of this vasodilator compound is
      associated with endothelial dysfunction, tissue hypoperfusion and
      atherosclerosis. Numerous studies indicate that the endothelium produces another
      class of compounds, the epoxyeicosatrienoic acids (EETs), which may partially
      compensate for the loss of nitric oxide in cardiovascular disease. The EETs are
      endogenous lipids which are derived through the metabolism of arachidonic acid by
      cytochrome P450 epoxygenase enzymes. Also, EETs hyperpolarize vascular smooth
      muscle and induce dilation of coronary arteries and arterioles, and therefore may
      be endogenous mediators of coronary vasomotor tone and myocardial perfusion. In
      addition, EETs have been shown to inhibit vascular smooth muscle migration,
      decrease inflammation, inhibit platelet aggregation and decrease adhesion
      molecule expression, therefore representing an endogenous protective mechanism
      against atherosclerosis. Endogenous EETs are degraded to less active
      dihydroxyeicosatrienoic acids by soluble epoxide hydrolase. Pharmacological
      inhibition of soluble epoxide hydrolase has received considerable attention as a
      potential approach to enhance EET-mediated vascular protection, and several
      compounds have appeared promising in recent animal studies. The present review
      discusses the emerging role of EETs in coronary vascular function, as well as
      recent advancements in the development of pharmacological agents to enhance EET
      bioavailability.

PMID- 16634833
TI  - New insights into the regulation of iron homeostasis.
AB  - Hepcidin evolves as a potent hepatocyte-derived regulator of the body's iron
      distribution piloting the flow of iron via, and directly binding, to the cellular
      iron exporter ferroportin. The hepcidin-ferroportin axis dominates the iron
      egress from all cellular compartments that are critical to iron homeostasis,
      namely placental syncytiotrophoblasts, duodenal enterocytes, hepatocytes and
      macrophages of the reticuloendothelial system. The gene that encodes hepcidin
      expression (HAMP) is subject to regulation by proinflammatory cytokines, such as
      IL-6 and IL-1; excessive hepcidin production explains the relative deficiency of
      iron during inflammatory states, eventually resulting in the anaemia of
      inflammation. The haemochromatosis genes HFE, TfR2 and HJV potentially facilitate
      the transcription of HAMP. Disruption of each of the four genes leads to a
      diminished hepatic release of hepcidin consistent with both a dominant role of
      hepcidin in hereditary haemochromatosis and an upstream regulatory role of HFE,
      TfR2 and HJV on HAMP expression. The engineered generation of hepcidin agonists,
      mimetics or antagonists could largely broaden current therapeutic strategies to
      redirect the flow of iron.

PMID- 16634834
TI  - Stem cells in the lung parenchyma and prospects for lung injury therapy.
AB  - Until recently, it was thought that only embryonic stem cells were pluripotent
      and that adult stem cells were restricted in their differentiative and
      regenerative potential to become the tissues in which they reside. However, the
      discovery that adult stem cells in one tissue can contribute to the formation of
      other tissues, especially after injury or cell damage, implies that stem cells
      have developmental plasticity. For example, haematopoietic stem cells (HSCs) and
      mesenchymal stem cells (MSCs) from bone marrow can be used to regenerate diverse
      tissues at distant sites, including the lung. This article reviews the character
      of stem cells in the lung parenchyma and focuses on the potential uses of adult
      stem cells in research of lung injury and lung disease therapies.

PMID- 16634835
TI  - Effects of smoking on cardiopulmonary baroreceptor activation and peripheral
      vascular resistance.
AB  - PATIENTS AND METHODS: We studied 16 healthy smokers and 16 nonsmokers acting as
      controls. We subjected smokers and nonsmokers to cardiopulmonary baroreceptor
      stimulation by studying forearm and common carotid haemodynamic and sympathovagal
      balance. Smokers repeated the tests after smoking one cigarette. Smokers and
      controls were subjected to passive elevation of the legs and the trunk in a
      horizontal position with pressure monitoring and measurement of the calibre and
      flow in the brachial and common carotid arteries using a colourDoppler
      ultrasound. We calculated forearm resistance and carotid wall tension. We also
      studied R-R variability, calculating the ratio between low frequency (LF) and
      high frequency (HF) R-R interval variability. RESULTS: During stimulation
      diastolic blood pressure values decreased in controls and in smokers at rest.
      After smoking one cigarette, smokers showed an increase in systolic and diastolic
      blood pressure as well as in the heart rate during stimulation. Humeral artery
      increased the calibre during stimulation in both groups; after cigarette smoking
      the calibre declined throughout the study phases. Forearm resistance decreased in
      both groups during stimulation at rest, but increased after cigarette smoking.
      The LF/HF ratio decreased during stimulation in both groups, and it increased at
      rest after smoking. Carotid diameter did not change in either group, and wall
      tension increased in smokers after smoking one cigarette. CONCLUSIONS: Smoking
      one cigarette increases resistance, impairs baroreflex and increases carotid wall
      tension in mild smokers. These findings may explain the higher rate of a
      cardiovascular event in smokers.

PMID- 16634836
TI  - Myocardial perfusion in patients with typical chest pain and normal angiogram.
AB  - BACKGROUND: Approximately 10-30% of patients with typical chest pain present
      normal epicardial coronaries. In a proportion of these patients, angina is
      attributed to microvascular dysfunction. Previous studies investigating whether
      angina is the result of abnormal resting or stress perfusion are controversial
      but limited by varying inclusion criteria. Therefore, we investigated whether
      microvascular dysfunction in these patients is associated with perfusion
      abnormalities at rest or at stress. PATIENTS AND METHODS: In 58 patients (39
      female, 19 male, mean age 58+/-10 years) with angina and normal angiogram as well
      as 10 control patients with atypical chest pain and normal coronaries (six
      female, four male, mean age 53+/-11 years) myocardial blood flow (MBF) was
      measured at rest and under dipyridamole using 13N-ammonia PET. Resting MBF and
      coronary flow reserve (CFR) as the ratio of hyperaemic to resting MBF were
      corrected for rate-pressure-product (RPP): normalized resting MBF
      (MBFn)=MBFx10,000/RPP and CFRn=CFRxRPP/10,000. RESULTS: Sixteen/58 patients had a
      normal CFRn (=2.5; group I; CFRn: 3.1+/-0.88); the same as the controls (CFRn:
      3.3+/-0.74). Forty-two/58 patients presented a reduced CFRn (group II; CFRn:
      1.78+/-0.57). Group II had both a higher MBFn (group II: 1.30+/-0.33 vs. Group I:
      1.03+/-0.26; P<0.05 and vs. controls: 1.07+/-0.19; P<0.01) and a lower hyperaemic
      MBF (group II: 2.25+/-0.76 mL g-1 min-1 vs. Group I: 3.07+/-0.78 mL g-1 min-1;
      P<0.001 and vs. controls: 3.41+/-0.94 mL g-1 min-1; P<0.0001). CONCLUSION:
      Impaired CFRn in patients with typical angina and normal angiogram is owing to
      both an increased resting and reduced hyperaemic MBF. Therefore, PET represents a
      prerequisite for further studies to optimize treatment in individuals with
      anginal pain and normal coronary angiogram.

PMID- 16634837
TI  - No effect of homocysteine-lowering therapy on vascular inflammation and
      haemostasis in peripheral arterial occlusive disease.
AB  - BACKGROUND: Although peripheral arterial occlusive disease (PAOD) is
      significantly associated with elevated homocysteine levels, the clinical
      relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is
      still unknown. MATERIALS AND METHODS: A total of 65 patients suffering from
      symptomatic PAOD with elevated homocysteine levels were randomized onto placebo
      or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg
      cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic
      acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP),
      interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and
      plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was
      reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL
      8, Il-18, MCP-1, TF and TFPI. RESULTS: The mean reduction of homocysteine
      concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8
      micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group.
      Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum
      group, but both remained unchanged in the control group. No treatment effect of
      lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation
      (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed. CONCLUSION: Although
      homocysteine is associated with vascular disease risk in the general population
      and in particular with PAOD, marked lowering of homocysteine concentrations by
      folic acid and B-vitamin supplementation does not influence inflammatory
      responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These
      results provide evidence against a major effect of hyperhomocysteinaemia on
      vascular chronic inflammation or coagulation in patients with symptomatic
      peripheral arterial occlusive disease.

PMID- 16634838
TI  - Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in
      diabetes mellitus type 2.
AB  - BACKGROUND: According to previous studies, cinnamon may have a positive effect on
      the glycaemic control and the lipid profile in patients with diabetes mellitus
      type 2. The aim of this trial was to determine whether an aqueous cinnamon
      purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma
      glucose, total cholesterol, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2
      diabetes. METHODS: A total of 79 patients with diagnosed diabetes mellitus type 2
      not on insulin therapy but treated with oral antidiabetics or diet were randomly
      assigned to take either a cinnamon extract or a placebo capsule three times a day
      for 4 months in a double-blind study. The amount of aqueous cinnamon extract
      corresponded to 3 g of cinnamon powder per day. RESULTS: The mean absolute and
      percentage differences between the pre- and post-intervention fasting plasma
      glucose level of the cinnamon and placebo groups were significantly different.
      There was a significantly higher reduction in the cinnamon group (10.3%) than in
      the placebo group (3.4%). No significant intragroup or intergroup differences
      were observed regarding HbA1c, lipid profiles or differences between the pre- and
      postintervention levels of these variables. The decrease in plasma glucose
      correlated significantly with the baseline concentrations, indicating that
      subjects with a higher initial plasma glucose level may benefit more from
      cinnamon intake. No adverse effects were observed. CONCLUSIONS: The cinnamon
      extract seems to have a moderate effect in reducing fasting plasma glucose
      concentrations in diabetic patients with poor glycaemic control.

PMID- 16634839
TI  - Fibrinolytic dysfunction in insulin-resistant women with previous gestational
      diabetes.
AB  - BACKGROUND: Women with a history of gestational diabetes (p-GDM) are at increased
      risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at
      increased risk for future cardiovascular disease. MATERIALS AND METHODS: Three
      months after delivery we investigated the plasma levels of plasminogen activator
      inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von
      Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal
      glucose tolerance during and after pregnancy, as well as the relation of
      fibrinolytic parameters to insulin resistance and glycaemic control. All women
      underwent an oral (OGTT) as well as an intravenous glucose tolerance test
      (FSIGT). Mathematical model analysis disclosed that 50% (n=37 each) of the p-GDM
      subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of
      interest were determined using commercially available test systems. RESULTS:
      Women with p-GDM and IIS had significantly increased body fat mass (BFM)
      (P<or=0.001) compared with women with p-GDM and NIS and controls, whereas the
      waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared
      with the controls (P<or=0.001). Mean PAI-1 and t-PA as well as fasting and
      stimulated plasma concentrations of proinsulin, C-peptide and insulin were
      elevated, whereas the disposition index was lower in women with p-GDM and IIS
      compared with women with p-GDM and NIS and the controls (P<0.001). Plasma levels
      of fibrinogen and vWF did not differ between the groups. Obese women with IIS had
      higher PAI-1 levels than lean women with IIS (P<or=0.001). PAI-1 inversely
      correlated with the insulin sensitivity index (SI) but only in women with IIS
      (P<0.0001). On regression analysis, only fasting proinsulin and WHR remained
      significant independent predictors of PAI-1 elevation in IIS (P<or=0.0001 and
      P<or=0.001). The PAI-1/SI ratio was elevated in women with IIS independently of
      their glucose tolerance status (P<0.001 vs. NIS and controls). CONCLUSIONS:
      Plasminogen activator inhibitor type 1 is elevated in p-GDM women with IIS and
      depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI
      ratio further characterizes obese insulin-resistant p-GDM women who may be at
      risk for diabetes and angiopathy.

PMID- 16634840
TI  - CREB transcription factor modulates Bcl2 transcription in response to C5a in HL
      60-derived neutrophils.
AB  - BACKGROUND: Complement fragment C5a and neutrophils have been implicated in the
      pathogenesis of renal disease and C5a has also been shown to delay apoptosis of
      human neutrophils via a transcription-independent pathway. However, transcription
      dependent pathways have not been well described. The present study examined
      whether activation of HL-60-derived neutrophils by C5a modulates the
      transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2
      (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein
      (CREB) transcription factor mediates these effects through the
      phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated
      kinase (ERK) signalling pathways. MATERIALS AND METHODS: The human promyelocytic
      leukaemia HL-60 cell line was differentiated into neutrophils using 1.25% DMSO.
      Differentiated cells were incubated with recombinant human C5a for 30-120 min
      with, or without, pretreatment with wortmannin or PD98059. The cells were lysed
      and quantified for gene-specific Bax and Bcl2 mRNA. In separate experiments,
      cells were incubated with C5a for 5-30 min with, or without, pretreatment with
      wortmannin, PD98059, or alkaline phosphatase. Cells were then lysed and
      immunoblotted using antihuman phospho-CREB (Ser133) antibody. Apoptosis was
      assessed by measuring active caspase-3 in differentiated HL-60 cells. RESULTS:
      C5a inhibited caspase-3 activation in HL-60-derived neutrophils (P=0.003). C5a
      significantly increased the expression of Bcl2 mRNA (P=0.028), which was time
      dependent, peaking at 30 min, and was abrogated in the presence of either
      wortmannin or PD98059 (both P=0.028). The C5a had no impact on Bax mRNA
      expression. The Bax : Bcl2 mRNA ratio markedly decreased at 30 min (P=0.028).
      Time-dependent effect of C5a on CREB phosphorylation was demonstrable and rapid,
      peaking at 5 min, and was abrogated by either wortmannin or PD98059 (both
      P=0.028). Phosphorylation of CREB, but not of Akt and ERK, was inhibited by
      alkaline phosphatase (P=0.028). The effect of C5a on Bcl2 mRNA expression was
      abrogated by alkaline phosphatase (P=0.028). The Bax : Bcl2 mRNA ratio markedly
      increased in the presence of alkaline phosphatase (P=0.046). CONCLUSIONS: This
      study demonstrates that C5a induces Bcl2 mRNA transcription in HL-60-derived
      neutrophils, which is mediated in part by CREB through the convergence of the
      PI3K/Akt and ERK-signalling pathways.

PMID- 16634841
TI  - Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Expired breath condensate (EBC) has never been used to explore the
      level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the
      aim of this study was to measure the levels of H2O2 and 8-isoprostane, as
      biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND
      METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the
      control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of
      all subjects and were compared between the IPF and control groups. In patients
      with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function
      tests (PFTs), the resting pO2 and the differential cell count from the
      bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of
      H2O2 was increased in the patients with IPF compared with the normal subjects
      (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI)
      concentration of 8-isoprostane was also increased in the patients with IPF
      compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In
      the patients with IPF, the diffusing capacity of the lung for carbon monoxide was
      negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other
      correlation was found between the oxidative stress markers in the EBC and PFT
      values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8
      isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated
      with the severity of the disease in IPF.

PMID- 16634842
TI  - Ethanol tolerance caused by slowpoke induction in Drosophila.
AB  - BACKGROUND: The large-conductance calcium-activated potassium channel encoded by
      the slowpoke gene has recently been implicated in the ethanol response.
      Caenorhabditis elegans carrying mutations in this gene have altered ethanol
      sensitivity and Drosophila mutant for this gene are unable to acquire rapid
      tolerance to ethanol or anesthetics. In Drosophila, induction of slowpoke
      expression has been linked to anesthetic resistance. METHODS: We used Drosophila
      as a model system to examine the relationship between slowpoke expression and
      ethanol tolerance. Real-time PCR and a reporter transgene were used to measure
      slowpoke induction after ethanol sedation. An inducible slowpoke transgene was
      used to manipulate slowpoke levels in the absence of ethanol sedation. RESULTS:
      Ethanol sedation increased transcription from the slowpoke neural promoters but
      not from the slowpoke muscle/tracheal cell promoters. This neural-specific change
      was concomitant with the appearance of ethanol tolerance, leading us to suspect
      linkage between the two. Moreover, induction of slowpoke expression from a
      transgene produced a phenotype that mimics ethanol tolerance. CONCLUSIONS: In
      Drosophila, ethanol sedation induces slowpoke expression in the nervous system
      and results in ethanol tolerance. The induction of slowpoke expression alone is
      sufficient to produce a phenotype that is indistinguishable from true ethanol
      tolerance. Therefore, the regulation of the slowpoke BK-type channel gene must
      play an integral role in the Drosophila ethanol response.

PMID- 16634843
TI  - Identification of miltirone as active ingredient of Salvia miltiorrhiza
      responsible for the reducing effect of root extracts on alcohol intake in rats.
AB  - BACKGROUND: Previous work found that extracts from the roots of Salvia
      miltiorrhiza, a Chinese medicinal herb, reduced alcohol intake in selectively
      bred Sardinian alcohol-preferring (sP) rats. The present study was designed to
      evaluate whether miltirone, one of the possible active constituents of S.
      miltiorrhiza, might be responsible for the reducing effect of the extracts on
      alcohol intake. METHODS: An initial experiment assessed the effect of 100 mg/kg
      (intragastric, i.g.) of 4 extracts of S. miltiorrhiza, differing in miltirone
      content (0, 2, 3, and 7%, respectively), on alcohol intake in alcohol-experienced
      sP rats exposed to the 2-bottle "alcohol (10%, volume in volume) versus water"
      choice regimen. Subsequently, the effect of pure miltirone (2.5-10 mg/kg, i.g.,
      i.e., a dose range comparable to its content in the effective doses of the active
      extracts) on acquisition and maintenance of alcohol-drinking behavior was
      evaluated in alcohol-naive and alcohol-experienced sP rats exposed to the 2
      bottle choice regimen. The effect of miltirone (10 mg/kg, i.g.) on blood alcohol
      levels was assessed after the i.g. and intraperitoneal (i.p.) administration of
      alcohol. Finally, the effect of miltirone (30-100 mg/kg, i.g.) on the severity of
      alcohol withdrawal syndrome was evaluated in Wistar rats made physically
      dependent on alcohol by the repeated administration of intoxicating doses of
      alcohol. RESULTS: The reducing effect of 4 different extracts of S. miltiorrhiza
      on alcohol intake was positively and significantly correlated with their
      miltirone content. Pure miltirone reduced alcohol intake in alcohol-experienced
      rats and delayed acquisition of alcohol-drinking behavior in alcohol-naive rats.
      Similar to S. miltiorrhiza extracts, miltirone markedly reduced blood alcohol
      levels when alcohol was administered i.g. but not i.p., suggesting that miltirone
      hampered alcohol absorption from the gastrointestinal system. Finally, miltirone
      failed to affect the severity of alcohol withdrawal syndrome in alcohol-dependent
      rats. CONCLUSIONS: The results of the present study suggest that miltirone is the
      likely active constituent of S. miltiorrhiza responsible for the reducing effect
      of its extracts on alcohol intake in different experimental models of excessive
      alcohol consumption.

PMID- 16634844
TI  - Working memory and decision-making biases in young adults with a family history
      of alcoholism: studies from the Oklahoma family health patterns project.
AB  - BACKGROUND: Alcohol misuse is more common in persons with a family history of
      alcoholism (FH+) than in those with no such history (FH-). Among FH+, behavioral
      disinhibition and male sex seem to signal the presence of an increased risk.
      METHODS: This study examined cognitive and behavioral characteristics of 175
      nonabusing 18- to 30-year-olds, 87 FH+ and 88 FH-, who were further characterized
      by their degree of behavioral disinhibition using the Sociability scale of the
      California Personality Inventory. Working memory and decision making were tested
      using the Stroop Color-Word Test and the Iowa Gambling Task, a simulated card
      game. RESULTS: Persons with a family history of alcoholism who were behaviorally
      disinhibited displayed significantly greater interference on the Stroop task than
      the other subgroups. On the Iowa Gambling Task, FH+ males, but not the females,
      were significantly more attentive to financial gains than other subgroups, and
      they had greater consistency in their choice behaviors. CONCLUSIONS: Persons with
      a family history of alcoholism, in combination with behavioral disinhibition,
      appears to signal working memory deficits and in combination with male sex
      indicates an attraction to the rewarding aspects of a risk-taking challenge.
      These findings are not secondary to heavy exposure to alcohol or other drugs, but
      instead reflect intrinsic risk-related familial and personal characteristics of
      the subjects.

PMID- 16634845
TI  - Heart rate response to alcohol and intoxicated aggressive behavior.
AB  - BACKGROUND: This study examined the elevated heart rate (HR) response to alcohol
      intoxication, thought to reflect an increased sensitivity to alcohol-induced
      reward, as a potential factor in the increased likelihood of alcohol-induced
      aggression. METHODS: Three groups, intoxicated high (n=37) and low (n=37) HR
      responders and sober controls (n=73), participated in a laboratory measure of
      physical aggression, the Taylor Aggression Paradigm. RESULTS: Results revealed
      that intoxicated high HR responders were more aggressive than the intoxicated low
      HR responders and sober controls. CONCLUSIONS: These findings are interpreted
      within a hypothetical model relating increased alcohol-induced aggression to a
      dysregulation in the motivational system responding to rewards.

PMID- 16634846
TI  - Topiramate does not affect the acquisition or expression of ethanol conditioned
      place preference in DBA/2J or C57BL/6J mice.
AB  - BACKGROUND: Topiramate, an anticonvulsant, has been reported to increase the
      number of abstinent days and decrease craving in alcohol-dependent individuals.
      However, the neurobiological basis for topiramate's effect is unknown. To assess
      topiramate's effect on ethanol's rewarding and conditioning rewarding effects,
      the present experiments examined the effects of topiramate on the acquisition and
      expression of ethanol-induced conditioned place preference (CPP) in DBA/2J and
      C57BL/6J mice. METHODS: A biased apparatus and subject assignment were used. Mice
      received ethanol (2 g/kg) or saline paired with an initially nonpreferred floor
      (CS+) and saline paired with an initially preferred floor (CS-) for 5-minute
      conditioning trials. During the acquisition experiments, mice received a
      pretreatment of topiramate (0, 5, 10, 20, 50, or 100 mg/kg) 1 hour before the CS+
      trials. On intervening CS- trials, mice received a pretreatment of saline. For
      the preference test, all mice received saline injections and were placed on a
      split floor for a 30-minute test. During the expression experiments, mice
      received no drug pretreatment on conditioning trials, but were pretreated with
      topiramate (0, 10, 50, or 100 mg/kg) 1 hour before the test session. RESULTS:
      Ethanol-induced CPP was observed in both strains, but topiramate did not affect
      the acquisition or expression of ethanol-induced CPP in either strain. Despite
      its failure to alter CPP, topiramate produced dose-dependent locomotor activating
      effects in both strains. These effects were observed both in the presence and in
      the absence of ethanol. CONCLUSIONS: These findings indicate that topiramate has
      no effect on ethanol's rewarding or conditioned rewarding effects as indexed by
      the place conditioning procedure. Thus, these studies raise the possibility that
      topiramate's efficacy in the treatment of alcoholism results from its impact on
      brain areas other than those that mediate ethanol's rewarding or conditioned
      rewarding effects. One alternative possibility is that topiramate decreases
      withdrawal-induced negative affective states that normally contribute to relapse.

PMID- 16634847
TI  - Overexpression of neuropeptide Y in the central nucleus of the amygdala decreases
      ethanol self-administration in "anxious" rats.
AB  - BACKGROUND: Neuropeptide Y (NPY) has been implicated in a variety of behaviors
      including those associated with anxiety and ethanol administration. The current
      experiment investigated the predictive role of anxiety-like behaviors in ethanol
      self-administration and the relationship of NPY in the central nucleus of the
      amygdala (CeA) with anxiety and ethanol self-administration. METHODS: Rats were
      divided into anxious and nonanxious groups based on behavior in the elevated plus
      maze. Following elevated plus maze testing, rats were allowed to consume
      increasing concentrations of ethanol (2, 4, and 6%) in a 2-bottle choice
      procedure over a period of 31 days. anxious rats showed an increased preference
      for 4% ethanol and 6% ethanol compared with non-anxious rats. Following 20-day
      access to 6% ethanol, rats underwent gene transfer surgery with replication
      defective recombinant herpes simplex 1 vectors encoding prepro-NPY, an antisense
      NPY RNA, or LacZ (control) into the CeA. RESULTS: In anxious rats, bilateral
      injections into the CeA with the NPY-antisense vector increased 6% ethanol
      preference, while the vector encoding NPY decreased 6% ethanol preference. Herpes
      simplex viral-mediated alterations in CeA NPY expression did not alter ethanol
      preference in nonanxious rats. CONCLUSIONS: These results suggest that virally
      mediated alterations in NPY levels in the CeA differentially affect ethanol
      consumption in rats with low and high basal levels of anxiety.

PMID- 16634848
TI  - Stress and alcohol consumption in heavily drinking men: 2 years of daily data
      using interactive voice response.
AB  - BACKGROUND: The relationship between stress and alcohol consumption has been
      shown in recent research to be more complex than originally thought. Cross
      sectional and short-term longitudinal studies may not provide adequate data to
      address subtle but important relationships that impact consumption frequency
      and/or quantity. METHODS: Participants were 33 males recruited from local bars
      who reported their alcohol consumption, stress, and other related variables every
      day for 2 years. Reports were provided by automated telephone to a computer-based
      interactive voice response (IVR) system. By closely monitoring call completion,
      we were able to collect over 95% of the daily calls. RESULTS: Using hierarchical
      linear modeling, daily stress was found to be associated with daily alcohol
      consumption, but in the opposite direction than would be predicted by a "drinking
      to cope" hypothesis. That is, same-day stress was found to be inversely related
      to consumption levels. Prior day's stress was not significantly associated with
      subsequent day's consumption; however, prior day's consumption was predictive of
      subsequent stress for up to 2 days. Similar analyses using week, rather than day,
      as the unit of measure paralleled these findings. CONCLUSIONS: This study
      highlights the utility of using long-term daily process data to address important
      research and clinical questions in the alcohol field.

PMID- 16634849
TI  - Ethanol and sucrose seeking and consumption following repeated administration of
      the GABA(B) agonist baclofen in rats.
AB  - BACKGROUND: Baclofen, a GABA(B) agonist, has been found to decrease alcohol
      craving in humans and to nonselectively decrease ethanol intake in some rodent
      models. This experiment assessed the effects of repeated administration of
      baclofen on reinforcer seeking and consumption using the sipper tube
      appetitive/consummatory model of ethanol access. METHODS: Subjects were divided
      into 2 groups and trained to make 30 lever press responses that resulted in
      access to either 10% ethanol or 2% sucrose in a sipper tube-drinking spout for 20
      minutes. Three doses of baclofen were tested (0.3, 1.0, and 3.0 mg/kg) and each
      drug treatment was assessed using the following schedule: Monday, saline; Tuesday
      to Thursday, baclofen; and Friday, saline. RESULTS: The low dose of baclofen had
      no effect on the seeking or intake of either sucrose or ethanol, and the 1.0
      mg/kg dose also had no effect on the appetitive, seeking response. However, the
      1.0 mg/kg dose significantly decreased sucrose intake (from an average of 0.56 to
      0.41 g/kg) and significantly increased ethanol intake (from an average of 0.77 to
      1.00 g/kg). Similarly, the high dose (3.0 mg/kg) decreased sucrose intake and had
      a tendency to increase ethanol intake while decreasing both sucrose seeking and
      ethanol seeking. CONCLUSIONS: Overall, baclofen treatment affected reinforcer
      intake at doses that had no effect on reinforcer seeking, and effective doses
      decreased both sucrose seeking and ethanol seeking. Moreover, the effects on
      reinforcer intake were disparate, in that baclofen increased ethanol drinking and
      decreased sucrose drinking. The nonspecific effects of baclofen suggest that the
      GABA(B) system may be involved in general consummatory or drinking behaviors and
      does not appear to specifically regulate ethanol-motivated responding.

PMID- 16634850
TI  - Alterations of rat corticostriatal synaptic plasticity after chronic ethanol
      exposure and withdrawal.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of chronic
      ethanol exposure (CEE) and withdrawal on corticostriatal plasticity in rats.
      METHODS: We established an animal model of alcoholism using the method of Turchan
      et al. (1999). A synaptic model of long-term memory (long-term depression, LTD)
      was used as an index and the striatum, which is related to habit learning, was
      selected as a target region in the present study. The effects of CEE and
      withdrawal on the LTD were studied in striatal slices of ethanol-dependent rats
      using the extracellular recording method. RESULTS: A stable LTD can be induced
      after high-frequency stimulation (HFS) in the slices of control rats. Chronic
      ethanol exposure and withdrawal suppressed the induction of corticostriatal LTD
      to different extents, with the strongest suppressive effects on LTD occurring in
      the slices of rats exposed to ethanol for 10 days and in those withdrawn from
      ethanol for 1 day. Notably, 3 days of withdrawal resulted in the shift of
      corticostriatal synaptic plasticity from LTD to long-term potentiation, and the
      peak latencies of the population spikes were obviously shortened compared with
      those of control rats. After 7 days of withdrawal, ethanol's effects tended to
      disappear. CONCLUSIONS: These results suggest that the alterations of
      corticostriatal synaptic plasticity produced by CEE and withdrawal may play a
      prominent role in alcohol abuse and alcoholism.

PMID- 16634851
TI  - Increased consumption but not operant self-administration of ethanol in mice
      lacking the RIIbeta subunit of protein kinase A.
AB  - BACKGROUND: Accumulating evidence indicates that adenosine monophosphate (cAMP)
      dependent protein kinase A (PKA) is involved in the neurobiological responses to
      ethanol. Previous reports indicate that mice lacking the RIIbeta subunit of PKA
      (RIIbeta(-/-)) voluntarily consume more ethanol than wild-type controls
      (RIIbeta(+/+)) using 2-bottle testing procedures. Although such procedures
      primarily measure consummatory behavior, operant self-administration procedures
      allow analysis of consummatory as well as appetitive or "ethanol-seeking"
      behavior (i.e., lever pressing is required to gain access to the ethanol
      solution). Therefore, we determined whether the high ethanol consumption
      characteristic of RIIbeta(-/-) mice would be complemented by increased appetitive
      ethanol-seeking behavior in an operant paradigm. METHODS: RIIbeta(-/-) (n=8) and
      RIIbeta(+/+) (n=8) mice were initially sucrose-faded until they were lever
      responding for nonsweetened ethanol (10, 14, and 18%). Following the self
      administration testing, RIIbeta(+/+) and RIIbeta(-/-) mice were given access to 2
      bottles, one containing water and the other ethanol to replicate the voluntary
      ethanol drinking data previously from our laboratory. Finally, immediately after
      voluntary consumption all mice were again tested for self-administration of 10%
      ethanol. Alterations in the reinforcement schedule were also explored as
      RIIbeta(+/+) and RIIbeta(-/-) mice were tested for self-administration of 10%
      ethanol at FR-3 and FR-5 schedules. RESULTS: The RIIbeta(-/-) mice displayed
      lower operant responding for ethanol and food reinforcement compared with
      RIIbeta(+/+) controls. However, this effect was driven by a significant increase
      in lever responses made by female RIIbeta(+/+) mice. When the excessive lever
      responses of the female RIIbeta(+/+) mice are accounted for, the RIIbeta(-/-)
      mice show ethanol lever responses comparable to controls. Following operant self
      administration testing, RIIbeta(-/-) mice of both sexes consumed more ethanol
      solution compared with RIIbeta(+/+) mice during 2-bottle testing. CONCLUSIONS:
      Increased ingestion of ethanol by RIIbeta(-/-) mice is likely the result of
      altered PKA activity within neuronal pathways that control ethanol-consummatory
      behaviors. Conversely, the RIIbeta subunit of PKA appears not to play a critical
      role in neuronal pathways that regulate appetitive behaviors directed at
      obtaining ethanol. Finally, increased operant self-administration of food and
      ethanol by female wild-type mice was absent in female RIIbeta(-/-) mice,
      suggesting that normal PKA signaling may be part of a general, and sex-dependent,
      mechanism involved with reinforcement-seeking behavior.

PMID- 16634852
TI  - Limited-access consumption of ascending ethanol concentrations in alcohol
      preferring, nonpreferring, and Sprague-Dawley rats.
AB  - BACKGROUND: Ethanol intake and preference differences between the selectively
      bred alcohol-preferring (P) and nonpreferring (NP) rats have generally been
      studied in a continuous-access paradigm using 10% ethanol. Little is known about
      the consumption of lower concentrations of ethanol in these lines or consumption
      of a wide range of ethanol concentrations in limited-access paradigms. Recently,
      limited-access paradigms have been used to study the biological and
      pharmacological mechanisms of ethanol consumption in animal models. Such research
      would be informed by studies investigating ethanol oral self-administration
      within a limited-access context. Therefore, the current study addressed P, NP,
      and Sprague-Dawley (SD) rats' consumption of a wide range of ethanol
      concentrations in a 2-bottle-choice, limited-access procedure. METHODS: Male P,
      NP, and SD rats were given concurrent access to water and ethanol solutions for 1
      h/d, 7 d/wk. Ethanol solutions were presented in an ascending series ranging from
      0.01 to 20% (v/v) over 55 days. Ethanol intakes (g/kg), volumes of solutions
      consumed (mL/kg), and preference ratios were assessed for each rat line at each
      concentration. RESULTS: Clear differences among the 3 types of rats emerged at an
      ethanol concentration of 4%, although differences between P and NP rats emerged
      at concentrations as low as 1.8%. Alcohol-preferring rats almost exclusively
      preferred ethanol solutions over water at ethanol concentrations of 4% and above,
      whereas SD and NP rats' preference ratios were more variable. CONCLUSIONS: The
      results suggest that differences between P and NP rats exist at ethanol
      concentrations lower than those previously studied in continuous-access
      paradigms. They also provide a current description of the ranges of ethanol
      concentrations preferred by P, NP, and SD rats.

PMID- 16634853
TI  - Influence of subjective intoxication, breath alcohol concentration, and
      expectancies on the alcohol-aggression relation.
AB  - BACKGROUND: The purpose of this study was to investigate the influence of
      subjective intoxication, alcohol-aggression expectancies, and breath alcohol
      concentration (BrAC) on intoxicated aggression in men and women while controlling
      for dispositional aggressivity. METHODS: Subjects were 328 (163 men and 165
      women) healthy social drinkers between 21 and 35 years of age. Following the
      consumption of either an alcohol or an active placebo beverage, subjects were
      tested on a modified version of the Taylor Aggression Paradigm in which mild
      electric shocks were received from, and administered to, a fictitious opponent
      during a competitive task. Levels of subjective intoxication and BrAC were
      measured immediately before subjects began the aggression task. Aggressive
      behavior was operationalized as the shock intensities administered to the
      fictitious opponent under conditions of low and high provocation. RESULTS:
      Subjective intoxication ratings were not related to aggressive behavior for
      either men or women. Alcohol-aggression expectancies were related to aggression
      for men, but this effect was rendered nonsignificant when controlling for
      dispositional aggressivity, which in turn, was significantly related to the
      dependent variables for both men and women. Finally, BrAC was also related to
      aggression above and beyond the effects of dispositional aggressivity, yet only
      for men. CONCLUSIONS: Taken as a whole, this study suggests that intoxicated
      aggression is primarily the result of alcohol's pharmacological properties in
      conjunction with an aggressive disposition.

PMID- 16634854
TI  - Chemical dependency patients with cooccurring psychiatric diagnoses: service
      patterns and 1-year outcomes.
AB  - BACKGROUND: Improving services and treatment outcomes for individuals with
      cooccurring alcohol and drug use disorders and psychiatric conditions has been a
      critical challenge to clinicians and policy makers. This study examined 1-year
      outcomes for individuals entering chemical dependency (CD) treatment with and
      without cooccurring psychiatric diagnoses targeted by California parity
      legislation. Among those with cooccurring conditions (i.e., dual-diagnosis
      patients), we examined a model including individual characteristics, treatment
      services, and extratreatment characteristics to understand CD outcome predictors
      in this population. We hypothesized that longer CD treatment duration and
      receiving psychiatric services would predict higher abstinence levels. In
      particular,patterns of psychiatric services (amount of services, receiving a
      critical dose, or receiving services concurrently with CD treatment) were
      assessed in relation to outcome. METHODS: We examined abstinence rates 1 year
      after intake for 747 adults with and without cooccurring conditions. Among dual
      diagnosis patients, logistic regression was used to examine predictors of
      abstinence. RESULTS: At baseline, dual-diagnosis patients (N=104) had higher
      levels of medical, family, and employment problems than others. They had similar
      CD retention and received more psychiatric services during the year after intake
      and had comparable CD outcomes at 1 year. Length of stay in CD treatment, hours
      of psychiatric services, number of months with concurrent CD and psychiatric
      services, and number of 12-step meetings attended were independent predictors of
      abstinence for dual diagnosis patients. CONCLUSIONS: Chemical dependency outcomes
      in patients with cooccurring psychiatric conditions were positively associated
      with the number and patterning of services. Receiving psychiatric services
      concurrently with CD treatment may be beneficial for dual-diagnosis patients.
      Future studies should examine how best to integrate services to optimize
      treatment outcomes.

PMID- 16634855
TI  - Targeted versus daily naltrexone: secondary analysis of effects on average daily
      drinking.
AB  - BACKGROUND: To extend our previous findings that naltrexone reduced the
      likelihood of heavy drinking on a given day among problem drinkers, while
      targeted administration reduced the likelihood of any drinking, we examined the
      effects of naltrexone and targeted administration on the continuous outcome of
      drinks/day. Because treatment response may differ by gender, we also compared the
      effects on this factor. METHODS: In a double-blind, placebo-controlled study,
      problem drinkers (n=150, 58% men) were randomly assigned to 8 weeks of treatment
      with naltrexone (50 mg/day) or placebo, either daily or on a targeted schedule.
      All subjects also received brief coping skills therapy. To complement the
      traditional regression analysis conducted previously, a zero-inflated Poisson
      regression model was used to examine the effects of medication, schedule of
      administration, and gender on the number of standard drinks consumed daily.
      RESULTS: Targeted naltrexone, and to a lesser extent targeted placebo, yielded a
      greater reduction in daily drinking than did daily placebo, an effect that did
      not differ by gender and that was greater than that seen for daily naltrexone
      treatment. Relative to daily placebo, daily naltrexone reduced the number of
      drinks/day only among men, at the level of a nonsignificant trend. CONCLUSIONS:
      Although in both genders, targeted treatments appeared to reduce the volume of
      drinking, treatment with targeted naltrexone was somewhat better. In contrast,
      heavy drinking women showed no benefit from daily naltrexone treatment. Further
      evaluation of the efficacy of targeted treatments and of daily naltrexone and the
      relationship of these treatments with gender is warranted.

PMID- 16634856
TI  - Suicidal behavior in alcohol-dependent subjects: the role of personality
      disorders.
AB  - BACKGROUND: Comobidity of personality disorders (PDs) and alcohol dependence are
      considered to increase the risk for suicidal behavior. The aim of this study is
      to assess the influence of Diagnostic and Statistical Manual of Mental Disorder
      fourth edition (DSM-IV) personality characteristics and comorbid axis I disorders
      on suicidal behavior in alcohol-dependent inpatients. METHODS: Characteristics of
      alcohol dependence and suicidal behavior were obtained using the Semi-Structured
      Assessment on Genetics in Alcoholism (SSAGA). Personality disorder
      characteristics were assessed using the Structured Clinical Interview for DSM-IV
      Axis II Disorders. RESULTS: Three-hundred seventy-six treatment-seeking alcohol
      dependent subjects, of whom 55% were diagnosed to have a PD and approximately 25%
      had a history of at least 1 suicide attempt, were enrolled into the study.
      Subjects with PDs in all clusters reported a higher rate of suicide attempt
      history, depression episodes, and depression during the most serious attempt. As
      indicated by univariate and multivarate analysis, this pattern of suicide attempt
      characteristics was most pronounced in borderline disordered subjects and
      alcoholic individuals who live alone. CONCLUSION: Subjects with alcohol
      dependence who have various comorbid PDs and depression deserve special attention
      in psychiatric care to prevent suicide. Psychotherapeutic strategies may have to
      be adapted to treat this high-risk population.

PMID- 16634857
TI  - Genetic polymorphism of CYP2E1 and digestive tract alcohol damage among Polish
      individuals.
AB  - BACKGROUND: Genetic polymorphism of enzymes involved in alcohol metabolism plays
      a relevant role in etiopathogenesis of alcohol disease. The aim of the present
      study was to find in the Polish population the CYP2E1 genotypes that are likely
      to be responsible for higher susceptibility to alcohol disease of the liver and
      chronic alcohol pancreatitis. METHODS: The CYP2E1 genotype and c1 and c2 alleles
      frequency were examined in 198 patients. Genotyping of the CYP2E1 was performed
      using polymerase chain reaction-restriction fragment length polymorphism methods
      on white cell DNA. RESULTS: In the examined population encompassing 198 subjects,
      the c2 allele was present only in 1.5% of patients. It was found only in patients
      abusing alcohol. In the group of patients with alcoholic cirrhosis, it was
      present in 3.5% of cases, whereas in patients with chronic alcoholic
      pancreatitis, in 2.3%. The genotype c1/c2 was present in 3% of subjects. The
      genotype c2/c2 was not found in any patient. Heterozygotes c1/c2 were present
      only in patients consuming excessive amounts of ethanol; in 7% of patients with
      alcoholic cirrhosis and in 4.5% of those with chronic alcoholic pancreatitis. The
      c2 allele occurred only in men. None of the examined women had the genotype
      c1/c2. CONCLUSIONS: Our studies suggest that the frequency of the c2 alleles in
      Polish population is low. Because of their rare frequency, it is difficult to
      conclude explicitly that the presence of the c2 allele promotes alcoholic damage
      to alimentary organs among Poles. It seems, however, that they pose the risk of
      alcoholic cirrhosis; their role in chronic alcoholic pancreatitis is difficult to
      assess.

PMID- 16634858
TI  - Ethanol-related smooth endoplasmic reticulum dilation in purkinje dendrites of
      aging rats.
AB  - BACKGROUND: Long-term ethanol consumption in aging rats results in degeneration
      and regression of the Purkinje neuron (PN) dendritic arbor. One marked ethanol
      related change in Purkinje dendrite ultrastructure is dilation of the smooth
      endoplasmic reticulum (SER) within PN dendritic shafts. The purpose of this study
      was to determine a time course for ethanol-related dendritic regression in PN
      dendritic shafts and spines. METHODS: One-hundred eighty aging, male Fischer 344
      rats were used. Four durations of treatment (5, 10, 20, and 40 weeks) and 3
      dietary treatment groups (60 rats/treatment group) were studied. Ethanol-fed rats
      received a liquid ethanol diet (35% of dietary calories from ethanol). Pair-fed
      rats received an isocaloric liquid control diet and chow-fed rats received rat
      chow and water ad libitum. After each duration of treatment, 45 rats
      (15/treatment) were euthanized and 2 posterior cerebellar lobules/rat were viewed
      with electron microscopy and photographed. Diameters of SER profiles within PN
      shafts and spines were measured with image analysis. RESULTS: Ethanol-related SER
      dilation in dendritic shafts occurred following 40 weeks of treatment. Ethanol
      related SER dilation was not detected in PN dendritic spines. CONCLUSIONS: These
      results confirm that ethanol-related dilation of SER profiles in PN dendritic
      shafts occurs following the same duration of treatment as the dendritic
      regression previously reported in other studies. Degenerating bodies that may be
      linked to dendritic regression were also identified in PN dendrites.

PMID- 16634859
TI  - Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal
      growth measures.
AB  - BACKGROUND: More than 3 decades after Jones and Smith (1973) reported on the
      devastation caused by alcohol exposure on fetal development, the rates of heavy
      drinking during pregnancy remain relatively unchanged. Early identification of
      fetal alcohol exposure and maternal abstinence led to better infant outcomes.
      This study examined the utility of biometry for detecting alcohol-related fetal
      growth impairment. METHODS: We obtained fetal ultrasound measures from routine
      ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in
      a brief alcohol intervention study. The fetal measures for women who quit after
      learning of their pregnancies were compared with measures for women who continued
      some drinking throughout the course of their pregnancies. Because intensity of
      alcohol consumption is associated with poorer fetal outcomes, separate analyses
      were conducted for the heavy (average of >or=5 drinks per drinking day) alcohol
      consumers. Fetal measures from the heavy-exposed fetuses were also compared with
      measures from a nondrinking group that was representative of normal,
      uncomplicated pregnancies from our clinics. Analyses of covariance were used to
      determine whether there were differences between groups after controlling for
      influences of gestational age and drug abuse. RESULTS: Nearly half of the
      pregnant drinkers abstained after learning of their pregnancies. When women
      reportedly quit drinking early in their pregnancies, fetal growth measures were
      not significantly different from a non-alcohol-exposed group, regardless of prior
      drinking patterns. Any alcohol consumption postpregnancy recognition among the
      heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial
      to body growth in comparison with women who either quit drinking or who were
      nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth
      ratios. CONCLUSIONS: Alterations in fetal biometric measurements were observed
      among the heavy drinkers only when they continued drinking after becoming aware
      of their pregnancies. Although the reliance on self-reported drinking is a
      limitation in this study, these findings support the benefits of early abstinence
      and the potential for ultrasound examinations in the detection of fetal alcohol
      effects.

PMID- 16634860
TI  - Alterations in circadian rhythm phase shifting ability in rats following ethanol
      exposure during the third trimester brain growth spurt.
AB  - BACKGROUND: Disruptions in sleep and feeding rhythms are among the consequences
      of prenatal alcohol exposure. Previously, we reported that ethanol exposure
      during the second trimester equivalent in rats produces long-lasting impairments
      in circadian system functioning. In the present study, we examined the effects of
      ethanol exposure during the third trimester equivalent brain growth spurt on the
      development of the circadian clock system. METHODS: Sprague-Dawley male rat pups
      were exposed to 6.0 g/kg/d ethanol via an artificial rearing procedure on
      postnatal days (PD) 4 through 9 (EtOH). An artificially reared gastrostomized
      control group and a normally reared suckle control group were also included. At
      10 to 12 weeks of age, wheel-running behavior was measured continuously under a
      12-hour/12-hour light/dark (LD) cycle. Thereafter, subjects were exposed to a 6
      hour phase delay of the LD cycle, and the ability to adjust to the new LD cycle
      was evaluated. RESULTS: Before the phase delay, onset time of activity and
      acrophases of activity in all 3 groups were not significantly different from one
      another. After the 6-hour LD cycle delay, EtOH subjects were slower to adapt to
      the new cycle compared with both control groups, as measured by both activity
      onset and acrophase. Throughout the experiment, activity levels of EtOH subjects
      tended to be higher compared to both controls. CONCLUSIONS: These data
      demonstrate that ethanol exposure during the third trimester disrupts the ability
      to synchronize circadian rhythm to light cues. Disruptions in circadian
      regulation may cause abnormal behavioral rhythmicity, such as disrupted sleep and
      feeding patterns, as seen in individuals prenatally exposed to ethanol.

PMID- 16634861
TI  - Chronic smoking and alcoholism change expression of selective genes in the human
      prefrontal cortex.
AB  - BACKGROUND: Alcoholism is commonly associated with chronic smoking. A number of
      gene expression profiles of regions within the human mesocorticolimbic system
      have identified potential alcohol-sensitive genes; however, the influence of
      smoking on these changes was not taken into account. This study addressed the
      impact of alcohol and smoking on the expression of 4 genes, previously identified
      as alcoholism-sensitive, in the human prefrontal cortex (PFC). METHODS: mRNA
      expression of apolipoprotein D, tissue inhibitor of the metalloproteinase 3, high
      affinity glial glutamate transporter and midkine, was measured in the PFC of
      alcoholic subjects and controls with and without smoking comorbidity using real
      time polymerase chain reaction. RESULTS: The results show that alcohol affects
      transcription of some of these genes. Additionally, smoking has a marked
      influence on gene expression. CONCLUSION: This study emphasizes the need for
      careful case selection in future gene expression studies to delineate the
      adaptive molecular process associated with smoking and alcohol.

PMID- 16634862
TI  - Toll-like receptors and innate antiviral immunity.
AB  - Viral infections are first detected by a set of innate immunity receptors that
      detect primary infections by pathogens, and trigger a transcriptional response.
      Among the induced target genes, type I interferons (IFNs) are central to the
      antiviral response of the host. The receptors and signaling pathways that mediate
      the strong induction of the synthesis of these cytokines have long remained
      elusive. In the past few years, Toll-like receptors (TLRs) emerged as important
      sensors of infections. Several TLRs participate in the recognition of virus
      infection, interacting in particular with viral nucleic acids. Upon activation,
      TLRs interact with different cytosolic adapter molecules and activate
      transcription factors of the nuclear factor-kappaB and IFN regulatory factor
      families that concur to mediate induction of IFN-alpha/beta and other
      inflammatory cytokines. In addition to the transmembrane TLRs, cytosolic
      helicases also detect viral nucleic acids, and trigger type I IFN synthesis.

PMID- 16634863
TI  - KIR3DL3 allelic diversity: six new alleles exhibit both conservative and non
      conservative substitutions.
AB  - KIR3DL3 alleles were characterized in two families and one unrelated individual.
      Based on exon 2-9 nucleotide sequences, six novel alleles, 3DL3*00402, *005,
      *006, *007, *00801, *00802, were identified bringing the total number of known
      alleles to 11. Compared with 3DL3*001, the six new alleles differ by from three
      to nine nucleotides and from three to four amino acids. The new alleles double
      the number of known polymorphic positions to 18 with variation in exons encoding
      the extracellular domains, transmembrane region, and a portion of the cytoplasmic
      tail. Many of the nucleotide substitutions are shared among alleles of 3DL3 or
      other KIR loci, but five were found only in single 3DL3 alleles. Comparison of
      intron sequences among individuals carrying the same allele showed a modest
      number of substitutions with the exception of 3DL3*001 which differed
      substantially in its intron sequences. Two alleles sharing coding region
      sequences, 3DL3*00201 and 3DL3*00202, were also substantially different in intron
      sequences.

PMID- 16634864
TI  - Haplotype associations of 90 rare alleles from the National Marrow Donor Program.
AB  - The National Marrow Donor Program maintains an HLA database of over 4.1 million
      US adult volunteers, 43,000 cord blood units, and 111,000 patients from which we
      identified 1,999,424 samples having allele-level HLA-A, HLA-B, or HLA-DRB1
      results. We analyzed 811 rare alleles reported at a frequency of less than 1 in
      50,000 in this study pool and found strong predicted haplotype associations for
      90 of them. The data set includes the number of times the allele was seen, the
      predicted haplotypes, and the racial or ethnic groups in which it was identified.
      This information can be helpful in designing search strategies for patients with
      rare alleles requiring hematopoietic stem cell therapy.

PMID- 16634865
TI  - Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to
      tuberculosis.
AB  - Genetic determinants of human susceptibility to tuberculosis (TB) have not been
      completely elucidated. Interleukin-1 beta (IL-1beta) and the inhibitor of kB-like
      (IkBL) are important molecules that participate in the inflammatory response
      required for the immunological control of a broad spectrum of infectious agents.
      The transporter associated with antigen processing (TAP) is involved in the
      antigen processing via major histocompatibility complex class I molecules and in
      turn might regulate the T-cell response against Mycobacterium tuberculosis. To
      better characterize the host genetic factors determining the susceptibility to
      TB, we evaluated the influence of functional polymorphisms in IL1B, TAP and IKBL
      genes on the risk of developing pulmonary TB in a Northwestern Colombian
      population, an endemic area of M. tuberculosis infection. A total of 122 TB
      patients and 166 healthy controls (N = 166) negative for human immunodeficiency
      virus infection were examined for IL1B-511 and +3,953, TAP1 and TAP2 and IKBL+738
      polymorphisms. Univariate analysis disclosed significant differences between
      patients and controls for IL1B+3,953 polymorphism. After unconditional logistic
      regression analysis, a strong protection conferred by IL1B+3,953 T-allele
      carrying genotypes was observed. A trend between TAP2*0201 allele and disease was
      observed. Association between IL1B-511, TAP1 or IKBL polymorphisms and TB disease
      was not found. These results indicate that a functional polymorphism in the IL1B
      gene influences the susceptibility to TB and suggest a role for IL-1beta in the
      pathogenesis of mycobacterial infection.

PMID- 16634866
TI  - Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian
      populations.
AB  - Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or
      long-tailed macaques, live across a vast range of South-East Asia. These non
      human primates have emerged as important animal models in infectious and chronic
      diseases and transplantation studies, necessitating a more extensive
      characterization of their major histocompatibility complex polymorphic regions.
      The current information on the polymorphic variation or diversity of the Mafa
      DPB1 locus is largely limited in comparison with the more commonly studied rhesus
      macaque DPB1 locus. In this article, to better elucidate the degree and types of
      polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East
      Asian populations and to investigate how the allele differences between macaques
      and humans might affect their respective immune responses, we identified 40
      alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217
      individuals. We also performed evolutionary and population analyses using these
      sequences to reveal some population-specific alleles and trans-species allelic
      conservation between the cynomolgus macaques and the rhesus macaques. Of the 40
      new alleles, eight belong to a newly identified lineage group not previously
      found in the rhesus macaque species. This allele information will be useful for
      medical researchers using the cynomolgus macaques in disease and immunological
      studies.

PMID- 16634867
TI  - Characterization and application of two novel monoclonal antibodies against human
      OX40: costimulation of T cells and expression on tumor as well as normal gland
      tissues.
AB  - OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor
      superfamily, is a critical costimulatory receptor during the immune response.
      Here, we newly generated two specific mouse antihuman OX40 monoclonal antibodies
      (mAbs) (2G2 and 1F7), whose specificities are quite different from the available
      OX40 mAb (ACT35) by competition assay. It was also found that both mAbs could
      enhance the proliferation, activation and differentiation of T lymphocytes primed
      by anti-CD3 mAb. These results evidenced that both were functional antihuman OX40
      mAbs. Furthermore, stained by 2G2 and 1F7, FCM and immunohistochemistry detected
      the constitutive expression of OX40 on tumor cell lines from epithelium, breast
      cancer and glioma tissues. Meanwhile, the non-tumor tissues (thyroid gland,
      stomach gland) were also found OX40 expression. These results suggested that OX40
      is not only expressed in activated T cells, but also in some tumors as well as
      normal gland tissues. Such expression pattern indicated that OX40 may be a
      valuable surface antigen in unveiling its expression and function outside the
      immune system. Briefly, these novel antibodies may contribute to the evaluation
      of the mechanism of tumor metastasis and eventually shed light on further study
      of tumor immunotherapy and autoimmune diseases.

PMID- 16634868
TI  - Identification of a novel 120 bp allele at the TNFd microsatellite locus.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine mainly
      secreted by macrophages and T-cells that play a key role in the pathogenesis of
      many infectious and inflammatory diseases. The TNF gene cluster is located within
      the class-III region of the highly polymorphic major histocompatibility complex
      on human chromosome 6p21. A cluster of six multiallelic microsatellites has been
      identified in the TNF region, named TNF a-e. TNFb, TNFc, TNFd, and TNFe are (GA)n
      repeats, whereas TNFa and TNFf are (GT)n and (CA)n repeats, respectively. The
      TNFd microsatellite locus maps 8-10 kb centromeric to the TNF-alpha gene,
      downstream to the TNF-beta gene.

PMID- 16634869
TI  - The identification of three novel MICA alleles by sequence-based typing.
AB  - During a study of MICA frequency in a healthy population and a cohort of patients
      suffering with inflammatory bowel disease, three DNA samples produced unusual
      reactivity patterns using polymerase chain reaction sequence-specific primers
      (PCR-SSP). These samples were subsequently characterized by sequence-based typing
      (SBT). Here, we report the sequence of these three novel MICA alleles.

PMID- 16634870
TI  - Inducible and endothelial nitric oxide synthase genes polymorphism in
      inflammatory bowel disease.
AB  - To assess the influence of inducible and endothelial nitric oxide synthase gene
      (NOS2A and NOS3) polymorphisms in susceptibility to Crohn's disease (CD) and
      ulcerative colitis (UC). A total of 505 inflammatory bowel disease (IBD) patients
      (221 with UC and 284 with CD) and 332 ethnically matched controls were studied.
      Patients and controls were genotyped by polymerase chain reaction -based
      techniques for a multiallelic (CCTTT)(n) repeat and biallelic marker (TAAA)(n) in
      the promoter region of the NOS2A gene and for a T/C polymorphism at position -786
      in the promoter region and a polymorphism in exon 7(298Glu/Asp) of the NOS3 gene.
      There was not association between NOS2A and NOS3 genotypes, alleles or haplotypes
      frequencies with UC, CD and controls. Our data suggest that NOS2A and NOS3
      polymorphisms do not play a major role in IBD predisposition.

PMID- 16634871
TI  - Cloning of rhesus monkey LILRs.
AB  - Leukocyte Ig-like receptors (LILRs) are a family of receptors that have
      inhibitory and activating functions and widely expressed by lymphoid and myeloid
      cells. Here we report the identification of the rhesus monkey LILRs by screening
      of rhesus spleen and decidua cDNA libraries and RT-PCR cloning. We obtained eight
      different full-length clones with structural and functional diversity similar to
      human LILRs, including LILRs with immunoreceptor tyrosine-based inhibitory
      motifs, LILRs with truncated cytoplasmic tails containing positively charged
      arginine residues in the transmembrane domain, and putative soluble receptors
      lacking transmembrane or cytoplasmic domains. Characterization of rhesus LILRs
      will facilitate use of this non-human primate model for the study of the
      functional role(s) of LILRs, including immune regulation through interaction with
      non-classical MHC class I molecules.

PMID- 16634872
TI  - Identification of an HLA-A*02 allele variant (A*0290) in a Chinese donor.

PMID- 16634873
TI  - Identification of a novel HLA-B allele HLA-B*4059 in Chinese bone marrow donors.

PMID- 16634874
TI  - A new HLA-B*27 allele, HLA-B*270402, identified by sequence-based typing.

PMID- 16634875
TI  - Identification of a novel HLA-B*39 allele, B*3936, by sequencing-based typing.

PMID- 16634876
TI  - Identification of a novel HLA-B*48 allele, B*4814, in a Chinese marrow donor of
      Han descent.

PMID- 16634877
TI  - A HLA-Cw*03 allele, Cw*0322Q with limited or no expression.

PMID- 16634878
TI  - Novel HLA-DRB1*1370 allele identified in a cord blood donor and her mother.

PMID- 16634879
TI  - 'Biologics': a clinically meaningless term.

PMID- 16634880
TI  - Chronic idiopathic urticaria with functional autoantibodies: 12 years on.
AB  - It is now recognized that approximately one-third of patients with chronic
      idiopathic urticaria (CIU) have histamine-releasing autoantibodies directed
      against either the high-affinity IgE receptor or, less frequently, against IgE.
      However, there are several unsolved problems relating to the role of such
      autoantibodies in the disease. Additionally, it is not clear whether CIU with
      autoantibodies can be classified as an autoimmune disease. The detection of
      patients with autoantibodies also poses challenges. Firstly, the only in vivo
      method, the autologous serum skin test, is at best 80% sensitive and specific
      using in vitro basophil histamine release assays as the verum. Secondly, in vitro
      tests are only done in a small number of research laboratories, and are not
      widely commercially available, and thirdly, there is some divergence between
      results obtained by different methods (functional and immunoassays) used to
      detect patients with autoantibodies. The presence of autoantibodies may be
      important clinically in a small group of severely affected, treatment-resistant
      patients, where immunomodulatory treatments may be helpful.

PMID- 16634881
TI  - Elevated prolidase activity in keloids: correlation with type I collagen
      turnover.
AB  - BACKGROUND: Keloid pathogenesis involves an altered balance of extracellular
      matrix metabolism, mainly accumulation of type I collagen. This could be due to
      excessive synthesis or decreased degradation of matrix, or a combination of both
      processes. Prolidase, an imidodipeptide-cleaving cytosolic enzyme, plays an
      important role in the collagen catabolic process by recycling proline for
      collagen synthesis. Collagen accumulation in keloids is due to an imbalance in
      the steady state of collagen turnover. OBJECTIVES: To investigate prolidase
      activity and its role in the steady state of collagen turnover between normal
      skin and keloid tissue and their derived fibroblasts. METHODS: Ten sets of keloid
      and normal skin tissues and their derived fibroblasts were employed. Measurements
      were made of tissue prolidase activity, free proline level, and concentrations of
      the collagen synthesis product aminoterminal propeptide of type I procollagen
      (PINP) and the collagen degradative product carboxyterminal telopeptide of type I
      collagen (ICTP). Also, synthesis of collagens type I and III and matrix
      metalloproteinases 1 and 2 was investigated using Western blot analysis. RESULTS:
      Keloid tissues had a significant increase in prolidase activity, up to fourfold
      that in normal skin. The elevated prolidase activity was accompanied by an
      increase in tissue PINP and ICTP concentrations in keloid; in addition, the
      collagen turnover index (PINP/ICTP) was higher in keloids. CONCLUSIONS: The
      combination of elevated prolidase activity and associated higher collagen
      synthesis to degradation ratio in keloids suggests a possible metabolic process
      for the excessive accumulation of type I collagen in keloids.

PMID- 16634882
TI  - Expression profiling of radiation-induced genes in radiodermatitis of hairless
      mice.
AB  - BACKGROUND: Radiation induces many cellular events leading to radiodermatitis.
      OBJECTIVES: The aim of this study was to establish a radiodermatitis model using
      experimental animals, and to examine the expression profile of radiation-induced
      genes. METHODS: Hairless mice were irradiated on the dorsal skin; then total RNAs
      were isolated and microarray hybridizations were performed. RESULTS: Irradiation
      with a total of 40 Gy (10 Gy day-1 for four consecutive days) provokes
      radiodermatitis in the hairless mouse. After microarray analysis, 130 genes that
      showed upregulation by radiation were selected and organized into four different
      clusters, depending on the time-kinetic pattern. Classification of these genes
      into several functional categories revealed that various biological processes
      were globally affected by radiation. These include transcription regulation,
      signal transduction, cell communication, cell death regulation and metabolism.
      CONCLUSIONS: These results demonstrate the complexity of the transcriptional
      profile of the radiation response, providing important clues on which to base
      further investigations of the molecular events underlying radiodermatitis.

PMID- 16634883
TI  - Absence of anti-BP180 antibodies in mothers of infants with bullous pemphigoid.
AB  - BACKGROUND: It is not clear whether bullous pemphigoid (BP) of infancy is linked
      to maternal transmission of pathogenic autoantibodies. Objectives To search for
      anti-BP180 antibodies in the sera of infants with BP and their mothers, using
      sensitive and specific methods. METHODS: Four infants (<6 months) with BP and
      their mothers were tested for anti-BP180 antibodies by indirect
      immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA).
      RESULTS: We found anti-BP180 antibodies in the sera of the four infants with all
      methods. These antibodies reacted with the extracellular domain NC16A. In the
      serum of their mothers we found 180 and 160 kDa proteins, each in one case, but
      indirect immunofluorescence and ELISA were negative, suggesting the absence of
      anti-BP180 autoantibodies reacting with the extracellular domain NC16A.
      CONCLUSIONS: BP of infants is not due to maternofetal transmission of pathogenic
      autoantibodies. Other hypotheses for the pathophysiology of BP are discussed.

PMID- 16634884
TI  - Measuring quality of life of patients with different clinical types of psoriasis
      using the SF-36.
AB  - BACKGROUND: Different specific and generic instruments are used to evaluate
      quality of life in dermatology, but their interrelationship is not well known.
      OBJECTIVES: To describe the quality of life in patients with different clinical
      types of psoriasis using the 36-item short form of the Medical Outcomes Study
      questionnaire (SF-36), and to study its correlation with dermatology-specific
      instruments. METHODS: We conducted a cross-sectional study of 380 inpatients with
      psoriasis. SF-36 mean scores were compared with the norms for medical and
      psychiatric disorders. Quality of life was also measured by both dermatology
      specific (Skindex-29 and Dermatology Life Quality Index, DLQI) and psoriasis
      specific instruments (Psoriasis Disability Index, PDI, and the Impact of
      Psoriasis Questionnaire, IPSO). A specific (Psoriasis Life Stress Inventory,
      PLSI) and a generic (12-item General Health Questionnaire, GHQ-12) measure of
      psychological distress was also used. A cluster analysis was performed to study
      the relationship among the different questionnaires. RESULTS: Our study
      population showed SF-36 physical health scores similar to minor medical
      conditions (e.g. physical functioning 79 for psoriasis, 80 for minor medical
      conditions, and 57 for severe medical conditions), but mental health scores quite
      similar to psychiatric illnesses (e.g. mental health 57 for psoriasis, 81 for
      minor medical conditions, 79 for severe medical conditions, and 53 for
      psychiatric conditions). The SF-36 showed two distinct patterns of impairment of
      quality of life, with a greater burden of disease for palmoplantar, pustular and
      arthropathic psoriasis. SF-36 scales tended to form separate clusters from the
      other dermatology-specific quality of life instruments. CONCLUSIONS: A generic
      quality of life instrument (e.g. the SF-36) provides information that is
      complementary to that derived from dermatological questionnaires, and may give
      further insight in the evaluation of the burden of psoriasis.

PMID- 16634885
TI  - HLA Cw*06 is not essential for streptococcal-induced psoriasis.
AB  - BACKGROUND: Streptococcal throat infections and HLA Cw6 (Cw*06) have been
      implicated in the pathogenesis of psoriasis, particularly in the guttate form.
      OBJECTIVES: To study 105 Irish patients with psoriasis to investigate the
      relationship between streptococcal infections and Cw*06. METHODS: The patients
      were divided into two groups: those with guttate psoriasis or guttate flare
      (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque
      group, CPG, n=41). RESULTS: The incidence of Cw*06 was 86% in the GG and 73% in
      the CPG, which was not significantly different (P=0.1725) but the incidence in
      both groups was significantly higher than in an Irish control group (18%)
      (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was
      higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with
      evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%)
      patients possessed the Cw*06 genotype. CONCLUSIONS: Thus, not all patients with
      streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if
      any, has yet to be determined.

PMID- 16634886
TI  - Distribution of Malassezia species in pityriasis versicolor and seborrhoeic
      dermatitis in Greece. Typing of the major pityriasis versicolor isolate M.
      globosa.
AB  - BACKGROUND: The expansion of the genus Malassezia has generated interest in the
      epidemiological investigation of the distribution of new species in a range of
      dermatoses, on which variable results have been reported from different
      geographical regions. No data are thus far available from South-east Europe
      (Greece). OBJECTIVES: To study the distribution of Malassezia species in
      pityriasis versicolor (PV) and seborrhoeic dermatitis (SD) and to investigate
      whether polymorphisms in the internal transcribed spacer (ITS) 1 region
      facilitate detection of M. globosa and M. sympodialis subtypes. METHODS: In
      total, 109 patients with PV and SD and positive Malassezia cultures were included
      in the study. Age, gender, primary/recurrent episode, disease extent and clinical
      form of PV were recorded. ITS 1 polymorphisms of M. globosa and M. sympodialis
      type and clinical strains were investigated by polymerase chain reaction (PCR)
      single-strand conformational polymorphism (SSCP) analysis. RESULTS: Malassezia
      globosa was the prevalent species isolated from PV and SD either alone (77% and
      39%, respectively) or in combination (13% and 18%, respectively) with other
      Malassezia species. The pigmented form of PV was strongly correlated with the
      female gender. PCR-SSCP differentiated five subgroups of M. globosa with one
      being associated with extensive clinical disease. All M. sympodialis isolates
      displayed a homogeneous ITS 1 PCR-SSCP profile. CONCLUSIONS: Malassezia species
      isolation rates were in agreement with those reported from South-west Europe. PCR
      SSCP of the ITS 1 is useful for highlighting prospective clinical implications of
      M. globosa subtypes.

PMID- 16634887
TI  - Plasminogen activator inhibitor-2 is expressed in different types of congenital
      ichthyosis: in vivo evidence for its cross-linking into the cornified cell
      envelope by transglutaminase-1.
AB  - BACKGROUND: Plasminogen activator inhibitor-2 (PAI-2), a regulatory serpin of the
      plasminogen activator (PA) system, has been described as a potential component of
      the cornified cell envelope (CE). Protease inhibitors are essential for skin
      homeostasis and in particular for the regulation of the desquamation process.
      Therefore, an aberrant expression of PAI-2 could be involved in the pathogenesis
      of certain cornification disorders. OBJECTIVES: Evaluation of the expression of
      PAI-2 in different types of congenital ichthyosis, especially in lamellar
      ichthyosis/nonbullous congenital ichthyosiform erythroderma (LI/NCIE) and in
      Netherton syndrome (NTS). Demonstration of the functional relationship between
      PAI-2 and transglutaminase (TGase)-1. PATIENTS AND METHODS: Using
      immunohistochemistry we evaluated cryosections from individuals suffering from
      LI/NCIE (n=67), NTS (n=6), ichthyosis-follicularis-atrichia-photophobia syndrome
      (n=2) and Harlequin ichthyosis (n=1) in comparison with psoriasis vulgaris and
      healthy skin. Moreover, we assessed the respective TGase-1 activity and the
      presence of TGase-1 protein. A functional assay was developed to elucidate
      whether PAI-2 is a substrate for TGase-1. RESULTS: PAI-2 is expressed in
      different types of congenital ichthyosis and there is a strong correlation
      between TGase-1 activity and PAI-2 protein signal. Double staining revealed a
      strong colocalization of TGase-1 activity and PAI-2 protein. The epidermal
      incorporation of the specific PAI-2 peptide containing a TGase binding site
      revealed a strong pericellular staining in the stratum granulosum in healthy
      skin. In contrast, TGase-1-deficient skin showed only a lamellar staining in the
      stratum corneum. CONCLUSIONS: We provide in vivo evidence that PAI-2 is a
      substrate of TGase-1. The normal expression of PAI-2 in a large group of TGase-1
      proficient LI/NCIE patients makes it rather unlikely that PAI-2 alone is a
      primary molecular cause of LI/NCIE.

PMID- 16634888
TI  - Skin lesions in adult liver transplant recipients: a study of 100 consecutive
      patients.
AB  - BACKGROUND: The surgical advances made in the area of organ transplantation along
      with the use of more efficacious immunosuppression have meant an increase in
      patient survival. This longer-living transplant population has started to exhibit
      cutaneous problems, some of which lead to an increased mortality while others
      lead to a decline in the quality of life. OBJECTIVES: The primary objective was
      to determine the different types of cutaneous lesions encountered in the adult
      liver transplant population. Secondary objectives were to determine the impact,
      if any, of the duration of transplant, the type of immunosuppression involved and
      the degree of sun exposure and skin phototype, on the skin cancers encountered in
      this transplanted population. METHODS: Two dermatologists examined 100
      consecutive liver transplant recipients (LTRs) attending the transplant
      outpatient department. Skin examination included the face and whole body and
      lesions found were categorized into the following groups: cutaneous malignancies,
      squamoproliferative lesions, cutaneous infections and others that did not fall
      into any of these categories. RESULTS: The reasons for organ transplantation were
      numerous. The mean age at transplantation was 42.5 years. The average time since
      transplantation was 5.5 (range 0.75-16 years). Four patients developed skin
      cancers; among them there were a total of seven skin cancers (one squamous cell
      carcinoma, six basal cell carcinomas). Fungal infections accounted for 19% of all
      cutaneous infections seen, viral infections 2% and bacterial infections 5%.
      Triple-drug immunosuppressive therapy (ciclosporin A, azathioprine and
      prednisolone) was used in 35% of LTR patients, while dual therapy (tacrolimus and
      prednisolone) was used in 48% and monotherapy (tacrolimus) was used in 17% of
      LTRs. CONCLUSIONS: Immunosuppressive therapy is believed to be one of the most
      important risk factors in the development of skin cancer in solid organ
      transplant recipients. The relatively low prevalence of skin cancer in our liver
      transplant population may in part be explained by the relatively high percentage
      of recipients on dual and monotherapy (48% and 17% respectively), and the shorter
      duration of therapy. Our study suggests that although LTRs are at higher risk of
      developing nonmelanoma skin cancer than the general population, the risk is
      comparable with other solid organ transplant recipients.

PMID- 16634889
TI  - Clinical selection of melanocytic lesions for dermoscopy decreases the
      identification of suspicious lesions in comparison with dermoscopy without
      clinical preselection.
AB  - BACKGROUND: In most cases dermoscopy is performed only on lesions selected by
      clinical inspection which present worrying clinical features or appear to deviate
      from the patient's average type of naevus. Thus, possible early malignant
      melanomas (MMs) or MM precursors, lacking typical clinical characteristics, may
      elude the dermoscopic examination. OBJECTIVES: To perform a comparison between
      two different approaches to the patient's examination, one based on a clinical
      preselection of lesions to be examined by dermoscopy, and the other consisting of
      the dermoscopic scrutiny of all melanocytic lesions with a diameter>or=2 mm
      (total dermoscopy). METHODS: Sixty-three consecutive patients with MM, undergoing
      periodic dermoscopic examinations of their naevi, were enrolled in the study. The
      patients first underwent an assessment of the entire skin with the unaided eye
      for the identification of lesions for dermoscopy. Subsequently, the patients
      underwent dermoscopic examination of all melanocytic lesions. Images of naevi
      identified by clinical examination or by total dermoscopy as having dermoscopic
      aspects characteristic of a suspicious lesion, i.e. necessitating either surgical
      excision or follow-up examinations, were separately recorded, classified and
      described employing the ABCD rule of dermoscopy and the seven-point checklist.
      RESULTS: Five hundred and fifty-one lesions were chosen by clinical inspection
      for subsequent dermoscopic examination; among these, 117 were considered for
      excision or follow-up. Ninety-two further lesions were identified for excision or
      follow-up by employing only total dermoscopy. Dermoscopy scores of lesions
      selected by clinical inspection plus dermoscopy were similar to those identified
      by dermoscopy alone. In the former group, 13 lesions showed either an ABCD or a
      seven-point score corresponding to a suspicious lesion, whereas eight such
      lesions were identified only by total dermoscopy. Thus, by clinical selection
      plus dermoscopy we were able to identify only 62% of dermoscopically suspicious
      lesions. CONCLUSIONS: Clinical selection of melanocytic lesions for dermoscopic
      examination is associated with the 'loss' of a conspicuous number of lesions
      which deserve surgical excision or follow-up examinations. Total dermoscopy,
      enabling the detection of suspicious lesions, together with storage, retrieval
      and sequential comparison of their images, could enhance MM diagnosis by follow
      up, in comparison with clinical preselection for dermoscopy.

PMID- 16634890
TI  - Induction of eruptive benign melanocytic naevi by immune suppressive agents,
      including biologicals.
AB  - BACKGROUND: Eruptive naevi have been described to potentially arise in immune
      compromised patients. OBJECTIVES: We describe three patients with eruptive benign
      melanocytic naevi during a phase of immunosuppressive therapy. METHODS/DIAGNOSIS:
      Two patients with Crohn disease were treated with either azathioprine monotherapy
      or a combination of azathioprine and infliximab, when eruptive naevi arose
      particularly at the palms and soles. Our third patient with plaque psoriasis
      developed eruptive naevi during two episodes of treatment: during a course with
      the biological agent alefacept and during etanercept therapy. CONCLUSIONS: We
      conclude that treatment with the recently available biological agents might be
      associated with the formation of eruptive naevi. Although positive evidence for
      the occurrence of malignant pigmented lesions is lacking, alertness to the
      development of eruptive melanocytic naevi during treatment with biological agents
      is indicated.

PMID- 16634891
TI  - Simultaneous sensitivity to fragrances.
AB  - BACKGROUND: Cinnamal/cinnamic alcohol and isoeugenol/eugenol are pairs of related
      fragrance chemicals found in Fragrance Mix I (FM I), and thus are routinely
      tested in combination with other fragrances in the European standard patch test
      series. Their close structural similarity makes the occurrence of simultaneous
      sensitivity within these chemical pairs likely, although at present there are no
      robust data to support this hypothesis. OBJECTIVES: To establish the frequency of
      simultaneous reactions to these fragrance chemicals in patients with suspected
      fragrance allergy attending a contact dermatitis clinic; to provide evidence in
      support of proposed metabolic pathways; and to determine whether including all
      four separately in FM I is necessary to avoid missing a diagnosis of fragrance
      allergy. METHODS: We analysed retrospectively the records of patients patch
      tested to the European standard series during the 15-year period 1984-98 for
      positive reactions to FM I. In a subset of patients tested to the constituents of
      FM I, positive reactions to cinnamal, cinnamic alcohol, isoeugenol and eugenol
      were sought. Data were analysed using 2x2 contingency tables (Fisher's exact
      test). RESULTS: During this period, 23,660 patients were tested to the European
      standard series, of whom 1811 (7.7%) had positive reactions to FM I. Of the 1112
      patients tested to the constituents of FM I, 934 had positive reactions to at
      least one constituent (total 1324 positive reactions to constituents). Of these
      934, 826 also had positive reactions to FM I itself; 108 were negative to FM I
      but reacted to one or more of its constituents. One hundred and seventy-eight
      patients did not react to any of the breakdown constituents of FM I; 34 of these
      had positive reactions to FM I itself. Of 139 patients allergic to cinnamic
      alcohol, 87 were also allergic to cinnamal (63%), compared with 108 (11.1%) of
      973 cinnamic alcohol-negative patients (P<0.00001). Of 231 patients allergic to
      isoeugenol, 50 were also allergic to eugenol (22%), vs. 109 (12.4%) of 881
      isoeugenol-negative patients (P=0.0002). CONCLUSIONS: These data support in vitro
      experiments indicating that cinnamal and cinnamic alcohol may generate a common
      hapten and are consistent with the view that simultaneous sensitization to
      isoeugenol and eugenol occurs to a limited extent, despite their being
      metabolized via different pathways. In view of the substantial number of isolated
      reactions to each of these fragrance chemicals, all four should continue to be
      included separately as constituents of FM I.

PMID- 16634892
TI  - Congenital naevi treated with erbium:YAG laser (Derma K) resurfacing in neonates:
      clinical results and review of the literature.
AB  - BACKGROUND: Giant congenital melanocytic naevi (CMN) are often disfiguring,
      potentially malignant pigmented lesions present at birth. Their management is
      based on two main considerations: attempt to minimize the risk of malignancy and
      to obtain an acceptable cosmetic result. In the past various approaches have been
      used to treat these naevi. OBJECTIVES: To describe clinical and histopathological
      results after treatment of CMN in neonates with erbium:YAG (Er:YAG) laser
      resurfacing. METHODS: Ten children with CMN were treated with Er:YAG laser
      resurfacing in the first weeks of life. RESULTS: Laser ablation was well
      tolerated by all children and immediate results were good. At a total follow-up
      ranging from 3 to 36 months we saw good results, with no or minimal
      repigmentation, in eight of 10 patients. Patients experienced minimal side
      effects such as postoperative pain, bleeding and scar formation. Postoperative
      histopathology showed disappearance of heavily pigmented cells in the upper part
      of the dermis. CONCLUSIONS: Er:YAG laser resurfacing is an effective method of
      ablating CMN, with minimal scarring and postoperative complications.

PMID- 16634893
TI  - The effect of ambient temperature on capillary vascular malformations.
AB  - BACKGROUND: Following pulsed dye laser (PDL) treatment of capillary vascular
      malformations (CMs), the capillaries left behind tend to be smaller and deeper.
      The PDL is most effective against capillaries over 50 microm, suggesting that
      clearance of CM could be improved by inducing capillary vasodilation of the
      smaller remaining capillaries. However, there are reduced perivascular nerves
      within CMs, implying that autonomic innervation to these capillaries may be
      abnormal. OBJECTIVES: To investigate whether CM capillaries will vasodilate in
      response to autonomic stimulation by raising ambient temperature. METHODS: Ten
      patients with untreated CMs and nine with previously laser-treated CMs were
      studied as ambient temperature was increased from 20 degrees C to 28 degrees C.
      The following measurements were taken at 2 degrees C intervals: skin blood flow
      (SBF); capillary diameter and depth; CM colour; and skin and core temperatures.
      RESULTS: All the subjects studied demonstrated superficial capillary vasodilation
      and increased SBF as the ambient temperature was raised from 20 degrees C to 28
      degrees C. Mean+/-SEM capillary diameter increased from 66+/-7 microm to 110+/-13
      microm (P<0.001) in the untreated group, compared with an increase from 28+/-5
      microm to 70+/-14 microm (P<0.001) in the treated group. Mean+/-SEM SBF increased
      from 427.2+/-98.2 perfusion units (PU) to 580.9+/-92.7 PU (P<0.01) in the
      untreated group, compared with an increase from 201.3+/-28.4 PU to 458.1+/-53.7
      PU (P<0.05) in the treated group. CONCLUSIONS: Superficial capillary vasodilation
      within CM is achievable by raising ambient temperature, including in those
      patients resistant to PDL treatment, potentially allowing further clearance of
      these lesions.

PMID- 16634894
TI  - Expression of chemokines and chemokine receptors in cutaneous CD30+
      lymphoproliferative disorders.
AB  - BACKGROUND: Little is known about the mechanisms involved in skin-specific homing
      in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine
      receptor interactions have been implicated in the homing of lymphoma cells to
      various tissue sites. OBJECTIVES: To investigate tissue samples from patients
      with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and
      CCR3 and their ligands MIG, TARC and RANTES. METHODS: Tissue samples from
      patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and
      lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on
      paraffin-embedded sections. Immunohistochemical analysis was also performed for
      CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of
      each skin specimen was stored at -80 degrees C and later examined using
      monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30.
      RESULTS: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a
      variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+
      atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative
      reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were
      occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid
      cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of
      LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12
      (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but
      in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma
      cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13:
      54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did
      not show a distinctive expression pattern in either disorder. CONCLUSIONS: We
      speculate that CCR3 is associated with the autocrine function in PCALCL, as
      evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP
      cells expressed CXCR3, which might support their migration towards the CXCR3
      ligand MIG, which is expressed in stromal cells of the skin.

PMID- 16634895
TI  - CXC chemokine receptor CXCR4 expression enhances tumorigenesis and angiogenesis
      of basal cell carcinoma.
AB  - BACKGROUND: Chemokines and their receptors, well known for their ability to
      attract leucocytes, also play important roles for tumour progression. OBJECTIVES:
      To investigate the possible involvement of chemokine receptors in the
      pathogenesis of cutaneous basal cell carcinoma (BCC). METHODS: We performed an
      expression analysis of chemokine receptors using a well-characterized human BCC
      cell line. Upon the finding of CXCR4 expression by BCC, retroviral transduction
      of BCC cells with the CXCR4 gene was employed to address its functional
      significance for BCC in vitro and in vivo. RESULTS: We found expression of the
      CXC chemokine receptor CXCR4 by a human cell line and a subset of tissue samples
      from BCC, especially in noduloulcerative and sclerosing types. Following
      treatment with CXCL12, the ligand for CXCR4, CXCR4-transduced BCC cells (CXCR4
      BCC) showed increased proliferation under low serum concentration and resistance
      to apoptosis induced by ultraviolet B irradiation in vitro. Conditioned media
      from CXCR4-BCC preincubated with CXCL12 enhanced tubule formation of human
      endothelial cells in vitro. These responses of CXCR4-BCC were negated by
      cotreatment with either neutralizing antibodies or specific blocking peptides for
      CXCR4 in vitro. Moreover, xenograft tumour transplants produced by injection of
      CXCR4-BCC yielded significant tumour progression in nude mice, whereas additional
      serial injections of CXCR4-blocking peptides resulted in tumour regression.
      CONCLUSIONS: CXCR4 expression may play a critical role in tumour progression and
      angiogenesis of certain subtypes of BCC with more aggressive nature, and
      functional blockade of CXCR4 could be a potential therapeutic strategy for these
      tumours.

PMID- 16634896
TI  - The expression levels and the differential expression of transforming growth
      factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are
      benign and intermediate malignant fibrotic dermal tumours, respectively. The
      contribution of transforming growth factor (TGF)-beta has been implicated in the
      progression of sclerosis in fibrotic diseases. OBJECTIVES: To investigate the
      expression of TGF-beta receptors in these fibrotic tumours. METHODS: We examined
      the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and
      TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical
      analysis. We also examined the expression of TGF-beta1 and collagen type I using
      immunohistochemical analysis. RESULTS: We detected strong expression of TGFbeta
      RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in
      vascular endothelial cells, smooth muscle cells and neural tissues, and weak
      expression in fibroblasts in normal skin sections. The expression levels of
      TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in
      comparison with normal dermal sections using in situ hybridization and
      immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and
      TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of
      TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their
      expression was found to be homogeneous in each DFSP tumour cell. The staining for
      TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF,
      and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal
      skin or tumour cells in the central part of DFSP. Type I collagen expression was
      found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP.
      CONCLUSIONS: These results suggest the possibility that TGF-beta signalling may
      contribute to the fibrosis around DF, and that TGF-beta receptors may play
      important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and
      TGFbeta-RII may be helpful in distinguishing these diseases.

PMID- 16634897
TI  - Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget
      disease.
AB  - BACKGROUND: Stat3 (Signal transducer and activator of transcription-3) is an
      oncogene that plays a critical role in regulating fundamental processes
      associated with malignant transformation and cell survival. It participates in
      oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL)
      and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin
      D1 protein has not been investigated in extramammary Paget disease (EMPD).
      OBJECTIVES: To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and
      cyclin D1 protein in EMPD and to evaluate the relationships among them. METHODS:
      Thirty-six tissue samples from 34 patients with primary EMPD were subjected to
      immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL. RESULTS: Thirty
      five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36
      and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In
      all of four invasive EMPD specimens, strong and frequent expression of these
      three molecules was evident; moreover, two invasive EMPD specimens with lymph
      nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two
      metastatic lymph node specimens showed very strong nuclear and local membrane p
      Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1
      expression and between p-Stat3 and Bcl-xL expression. CONCLUSIONS: Our study
      shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal
      role in the pathogenesis of EMPD.

PMID- 16634898
TI  - Interdigital lesions and frequency of acute dermatolymphangioadenitis in
      lymphoedema in a filariasis-endemic area.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne nematode infection that
      causes permanent lymphatic dysfunction in virtually all infected individuals and
      clinical disease in a subset of these. One major sequel of infection is
      lymphoedema of the limbs. Lymphoedema of the leg affects an estimated 15 million
      persons in LF-endemic areas worldwide. Acute dermatolymphangioadenitis (ADLA) in
      people with filarial lymphoedema causes acute morbidity and increasingly severe
      lymphoedema. Episodes of ADLA are believed to be caused by bacteria, and it has
      been shown that entry lesions in the skin play a causative role. Clinical
      observations suggest that interdigital skin lesions of the feet, often assumed to
      be fungal, may be of particular importance. OBJECTIVES: To investigate the
      epidemiology and aetiology of interdigital lesions (IDL) of the feet in filarial
      lymphoedema. METHODS: The frequency and mycological aetiology of IDL in 73
      patients with filarial lymphoedema were compared with 74 individuals without
      lymphoedema in a region of Guyana highly endemic for Wuchereria bancrofti.
      RESULTS: More than 50% of patients with lymphoedema had one or more IDL (odds
      ratio 2.69; 95% confidence interval 1.31-5.66; P<0.005 compared with controls).
      The number of lesions was the strongest predictor of frequency of ADLA. Only 18%
      of the lesions had positive microscopy or culture for fungi (dermatophytes and
      Scytalidium). CONCLUSIONS: These findings highlight the importance of
      interdigital entry lesions as risk factors for episodes of ADLA and have
      implications for the control of morbidity from filarial lymphoedema.

PMID- 16634899
TI  - The effect of dermatology consultations in secondary care on treatment outcome
      and quality of life in new adult patients with atopic dermatitis.
AB  - BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing worldwide, and
      many patients present to secondary care in adult life. This is a significant
      contribution to the workload of all dermatology departments. There are no studies
      investigating the impact of a dermatology consultation within secondary care.
      OBJECTIVES: To examine the effect of dermatology consultations in secondary care
      on treatment outcome and quality of life in new adult patients with AD. METHODS:
      This prospective observational study recruited new adult patients with AD
      referred from primary care. Eczema severity was assessed using the SCORAD
      (Severity Scoring of AD) index and subjective good or poor clinical outcome. The
      Dermatology Life Quality Index (DLQI) was used to quantify the impact of AD on
      adult patients. Patients were assessed at initial consultation (T1), 6 weeks (T2)
      and 3 months (T3). Statistical analysis was performed using independent t-tests,
      repeated-measures analysis of variance, correlation coefficients and Bonferroni
      post hoc comparisons. RESULTS: Sixty-three patients were recruited (37 women, 26
      men) with a mean age of 34 years. Mean SCORAD at T1 was 48.2 and the majority
      (51%) had severe eczema (objective SCORAD>40). Mean SCORAD reduced by 52% from T1
      to T2 (P<0.001) but there was no significant change in SCORAD from T2 to T3. A
      subjective good clinical outcome was validated by a decrease in SCORAD of >20
      (P<0.001). Patients in the good clinical outcome group were significantly older
      than those in the poor clinical outcome group (38 vs. 27 years, P<0.05). The mean
      age at presentation of women was significantly younger than men (29 vs. 43 years,
      P<0.01). Women's mean SCORAD improved over all three visits, while men's mean
      SCORAD improved from T1 to T2 but worsened from T2 to T3 (P<0.001). The mean DLQI
      reduced over all three visits, from 9.5 at T1 to 8.8 at T2 and 7.0 at T3, and was
      significantly correlated with SCORAD at T1 and T2 (P<0.01). Patients accurately
      self-scored their eczema on a body map as shown by a significant correlation
      between these scores and SCORAD at T1 and T2 (P<0.001). CONCLUSIONS: We have
      shown that within the first 3 months of referral to secondary care, new adult
      patients with AD have the greatest improvement in AD, measured by SCORAD, after
      their initial appointment. Quality of life, as measured by DLQI, continued to
      improve over all three visits.

PMID- 16634900
TI  - Food and Drug Administration surveillance of dermatology-related and
      nondermatology-related prescription drug advertising in the USA, 2000-2003.
AB  - BACKGROUND: Spending on advertising of prescription medicines in the U.S.A. is
      increasing by nearly a billion dollars yearly. The Food and Drug Administration
      (FDA) is legally mandated to regulate pharmaceutical advertising in the U.S.A.
      Prior studies have documented inaccuracies in pharmaceutical advertisements, in
      the U.S.A. and the rest of the world. OBJECTIVES: To assess trends in FDA
      surveillance of dermatology-related prescription drug advertising, and to
      investigate pharmaceutical companies' responses to FDA regulatory actions.
      METHODS: We analysed all FDA citations of prescription drug advertisements issued
      during 2000-2003, and responses from cited companies to our mailed requests for
      follow-up information. RESULTS: Twenty-four dermatology-related drugs from 21
      companies accounted for 30 (15.2%) of the 198 letters sent by the FDA; of these,
      18 letters cited advertisements or promotions of these medications for
      dermatology-related uses. The most common violation cited overall was
      insufficient communication of risk (32.4% overall, 33.9% dermatology-related).
      Most FDA letters cited physician-targeted advertising (71.6% overall, 62.1%
      dermatology-related). The number of dermatology-related letters sent declined by
      69.2% from 2000 (n=13) to 2003 (n=4), paralleling the 69.6% decline in the total
      number of letters sent (n=79 in 2000, n=24 in 2003). Compared with 2000, the FDA
      took longer to issue citation letters in 2003 for advertisements overall [hazard
      ratio (HR) 0.47, 95% confidence interval (CI) 0.27-0.72, P=0.001], although this
      trend was not present for dermatology-related advertisements (HR 1.12, 95% CI
      0.39-3.29, P=0.83). Eight of the 16 companies (50%) that received requests from
      the authors for information replied. Seven of the eight (87.5%) reported
      complying with FDA requests to discontinue the cited advertisements, while one
      (12.5%) reported disagreeing with the citation and successfully clarifying the
      issue with the FDA. CONCLUSIONS: Dermatology-related advertisements accounted for
      15.2% of FDA citations of pharmaceutical advertisements between 2000 and 2003.
      Recent controversy over pharmaceutical advertising may lead to changes in
      pharmaceutical advertising practices and surveillance of pharmaceutical
      advertising in the U.S.A.

PMID- 16634901
TI  - Bone mineralization in children with epidermolysis bullosa.
AB  - BACKGROUND: Various factors may have deleterious effects on bone health in
      patients with epidermolysis bullosa (EB). OBJECTIVES: In a retrospective notes
      review, to assess bone mineralization in children with EB and to identify the
      relative contributions of nutrition, activity and disease severity to low bone
      mass. METHODS: Thirty-nine children with EB [32 recessive dystrophic EB (RDEB),
      four Dowling-Meara EB simplex (DMEBS) and three junctional EB (JEB)] had lumbar
      spine bone mass measured using dual X-ray absorptiometry (GE Lunar Prodigy; GE
      Healthcare, Chalfont St Giles, U.K.). Seventy-six healthy children were also
      studied. Weight and height were recorded and mobility was rated. RESULTS:
      Children with RDEB and JEB, but not those with DMEBS, had lower bone mineral
      density SD scores than controls; differences remained after adjusting for the
      smaller body size of the patients. Bone mass was best predicted by mobility
      rating. CONCLUSIONS: Children with RDEB and JEB have low bone mass after
      adjusting for their smaller size, which may put them at risk for fragility
      fractures. Low bone mass was best predicted by the level of mobility, raising the
      hypothesis that improving activity or bone loading may be a potential preventive
      intervention in these children. However, as low bone mass may be multifactorial
      in these children, more detailed investigation of potential aetiological factors
      is required before interventions are planned.

PMID- 16634902
TI  - Modulation of ultraviolet (UV) transmission by emollients: relevance to
      narrowband UVB phototherapy and psoralen plus UVA photochemotherapy.
AB  - BACKGROUND: Patients with psoriasis undergoing or about to undergo ultraviolet
      (UV) phototherapy and photochemotherapy often have thick scale on their plaques
      which can prevent the penetration of UV radiation. Emollients are used to
      moisturize the skin and to prevent or reduce some of the milder side-effects
      ('dryness', itching) sometimes experienced during UV therapy. However, emollients
      can alter the UV transmission of skin and thus may alter the clinical effects of
      phototherapy and photochemotherapy. OBJECTIVES: We tested 30 of the topical
      emollients in the British National Formulary (BNF) using a standard in vitro
      technique used to test sunscreens. We also surveyed U.K. phototherapy units to
      establish routine practice for emollient use in phototherapy and
      photochemotherapy. METHODS: We used a standard in vitro technique to measure the
      monochromatic protection factors (MPFs) of 30 non-bath emollients from the BNF.
      An application rate of 2 mg cm-2 was used. For the assessment of effects during
      narrowband UVB (TL-01) phototherapy, the mean of the protection factors at 310
      and 315 nm was calculated; for psoralen plus UVA photochemotherapy the mean UVA
      protection factor was used. A questionnaire survey was used to assess routine
      practice concerning emollient use prior to phototherapies in phototherapy units
      throughout the U.K. RESULTS: In the UVA range, 17 of the 30 emollients gave
      protection factors of 1.2 or above. In the UVB range, 23 of 30 had an MPF of 1.2
      or above. Yellow soft paraffin had the highest protection factor in the UVB
      range. Of 78 centres surveyed, 57 returned completed questionnaires (73%).
      Seventeen of 57 (30%) centres routinely used emollients immediately prior to
      administering phototherapy treatments. The remaining 40 of 57 (70%) did not.
      Forty-five (79%) responding centres recommended the use of emollients after
      phototherapy. CONCLUSIONS: This study has revealed considerable variability in
      the practice of emollient use before phototherapy treatments. Although the
      majority of centres included in this study did not routinely use emollients,
      almost one third did. Our in vitro measurement of 30 emollients revealed marked
      variation in UV transmission, with many emollients blocking sufficient UV to
      affect the response to therapy.

PMID- 16634903
TI  - Photodynamic therapy of acne vulgaris using methyl aminolaevulinate: a blinded,
      randomized, controlled trial.
AB  - BACKGROUND: Inflammatory acne vulgaris is a very common condition, particularly
      in adolescents and young adults, and new effective and well-tolerated treatments
      are needed. OBJECTIVES: To evaluate the efficacy and tolerability of methyl
      aminolaevulinate-based photodynamic therapy (MAL-PDT) in patients with moderate
      to severe facial acne vulgaris in a randomized, controlled and investigator
      blinded trial. METHODS: Twenty-one patients were assigned to the treatment group
      and 15 patients to the control group. The treatment group received two MAL-PDT
      treatments, 2 weeks apart. Both groups were evaluated 4, 8 and 12 weeks after
      treatment. Efficacy evaluation included changes from baseline in numbers of
      noninflammatory and inflammatory lesions, changes from baseline in global acne
      severity grade and clinical assessments of clinical improvement by patient and
      evaluating dermatologist. Pain scores during treatment and local adverse effects
      were also evaluated. RESULTS: Twelve weeks after treatment the treatment group
      showed a 68% reduction from baseline in inflammatory lesions vs. no change in the
      control group (P=0.0023). We found no reduction in number of noninflammatory
      lesions after treatment. All patients experienced moderate to severe pain during
      treatment and developed severe erythema, pustular eruptions and epithelial
      exfoliation. Seven patients did not receive the second treatment due to adverse
      effects. CONCLUSIONS: MAL-PDT proved to be an efficient treatment for
      inflammatory acne. The treatment was associated with severe pain during treatment
      and severe adverse effects after treatments. Efforts must be made to optimize the
      treatment regimen and to avoid adverse effects.

PMID- 16634904
TI  - Clindamycin and rifampicin combination therapy for hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory condition
      affecting apocrine gland-bearing areas of the skin. There is currently no
      satisfactory treatment. OBJECTIVES: To assess the efficacy of a 10-week course of
      combination clindamycin 300 mg twice daily and rifampicin 300 mg twice daily in
      the treatment of HS. METHODS: Patients who had received combination therapy with
      clindamycin and rifampicin for HS at one U.K. Dermatology Centre between the
      years 1998 and 2003 were identified from pharmacy records. Their records were
      analysed retrospectively. RESULTS: Fourteen patients with HS had received
      treatment with combination therapy. Eight of these patients achieved remission
      and a further two achieved remission when minocycline was substituted for
      clindamycin. Four patients were unable to tolerate therapy. CONCLUSIONS: This
      small retrospective study indicates that combination therapy with clindamycin and
      rifampicin may be effective for HS. However, there is a need for a placebo
      controlled trial.

PMID- 16634905
TI  - An exploratory prospective observational study of environmental factors
      exacerbating atopic eczema in children.
AB  - BACKGROUND: Possible exacerbating factors are a major concern of parents of
      children with atopic eczema (AE). However, there is minimal evidence for their
      direct role in leading to disease flares. OBJECTIVES: To assess the association
      between 'trigger factors' and disease flares in AE. METHODS: Twenty-five children
      with AE were recruited. Participants completed diaries, recording severity and
      exposure to potential exacerbating factors (18 variables) over 28 days. Severity
      was assessed at baseline and study completion. The relationship between severity
      and exposures was assessed. RESULTS: At episode level, on the day of exposure
      (lag 0), hot weather correlated to increased scratch scores (P=0.043). At a lag
      of 2 days after exposure, damp weather was associated with raised scratch scores
      (P=0.027). At lag 3 days, elevated scratch scores were associated with sweating
      and stress (P=0.029 and 0.019, respectively). Outside damp was associated with
      elevated scores (P=0.001) at lag 4. Multivariate analysis of all significant
      variables showed that only damp at lag 4 was significantly associated with flares
      (P=0.039). CONCLUSIONS: This study suggests association between stress, damp and
      heat and disease flares. These findings need to be studied over a longer period,
      using objective exposure measures.

PMID- 16634906
TI  - Chronic lymphocytic leukaemia skin infiltrates affecting prominent parts of the
      face and the scalp.
AB  - Chronic lymphocytic leukaemia (CLL) infiltrating the skin is uncommon and can
      present in different forms. We report a case of CLL infiltrating the prominent
      parts of the face and the scalp. A 63-year-old male with a 10-year history of CLL
      presented with plum-coloured swelling of the skin of the ears, eyebrows, tip of
      the nose and the scalp. Histopathology showed dense sheets of lymphoid infiltrate
      of the dermis which stained positive with B-cell markers CD20 and CD5 in keeping
      with the infiltrate of CLL.

PMID- 16634907
TI  - Detection of COL1A1-PDGFB fusion transcripts and platelet-derived growth factor
      alpha and beta receptors in giant cell fibroblastoma of the postsacrococcygeal
      region.
AB  - We describe a 2-year-old girl with recurrent giant cell fibroblastoma (GCF) of
      the postsacrococcygeal region. Both the initial and recurrent tumours contained
      solid and angiectoid areas. The former was composed of loosely arranged wavy
      spindle cells and giant cells with a well-vascularized myxoid to collagenous
      stroma. The angiectoid spaces were often lined by multinucleated giant cells.
      Immunohistochemically, the tumour cells and small vessels in the tumour tissue
      were positive for platelet-derived growth factor (PDGF) alpha and beta receptors.
      Molecular analysis revealed fusion of collagen type Ialpha1 exon 26 with PDGF-B
      chain exon 2 that induced unscheduled production of PDGF-BB. These findings
      suggest that PDGF and its receptors significantly contribute to the development
      of GCF in both an autocrine and a paracrine manner.

PMID- 16634908
TI  - Regression of extranodal natural killer/T-cell lymphoma, nasal type with
      denileukin diftitox (Ontak) and bexarotene (Targretin): report of a case.
AB  - Denileukin diftitox (Ontak) is a fusion protein comprising a diphtheria toxin and
      an interleukin (IL)-2 moiety that specifically targets CD25 (IL-2 receptor)
      positive tumour cells. We report a patient with rapidly progressive Epstein-Barr
      virus-positive nasal type extranodal natural killer/T-cell lymphoma (extranodal
      NKTCL), treated with a combination of denileukin diftitox (Ontak) and oral
      bexarotene (Targretin). A significant regression of the cutaneous tumours was
      observed already after the first cycle of denileukin diftitox and was maintained
      for a period of 5 months with monthly cycles of denileukin diftitox. The
      treatment was well tolerated. Following this response the patient decided to stop
      the treatment. He was then followed by his oncologist and lost from
      dermatological follow-up. Shortly after treatment withdrawal the disease
      progressed and the patient received one cycle of doxorubicin (Caelyx). He died
      from septic shock syndrome 2 months later. To our knowledge this is the first
      case of extranodal NKTCL treated with denileukin diftitox and bexarotene. A
      striking, albeit transient, response occurred with this therapy. Combination
      treatment with denileukin diftitox and bexarotene should be further assessed in
      this aggressive type of cutaneous lymphoma.

PMID- 16634909
TI  - A case of Brooke-Spiegler syndrome with a new mutation in the CYLD gene.

PMID- 16634910
TI  - A novel indel COL7A1 mutation 8068del17insGA causes dominant dystrophic
      epidermolysis bullosa.

PMID- 16634911
TI  - Adalimumab causing vasculitis.

PMID- 16634912
TI  - Venlafaxine-associated psoriasiform palmoplantar keratoderma and subungual
      hyperkeratosis.

PMID- 16634913
TI  - Successful treatment of systemic sclerosis-related digital ulcers and sarcoidosis
      with endothelin receptor antagonist (bosentan) therapy.

PMID- 16634914
TI  - Eccrine angiomatous hamartoma of the fingers with nail destruction.

PMID- 16634915
TI  - Extensive mucinous eccrine naevus following the lines of Blaschko: a new type of
      eccrine naevus.

PMID- 16634916
TI  - Elevated circulating CD40 ligand in patients with erythema multiforme and Stevens
      Johnson syndrome/toxic epidermal necrolysis spectrum.

PMID- 16634917
TI  - Multiple hereditary infundibulocystic basal cell carcinomas: a distinctive
      genodermatosis.

PMID- 16634918
TI  - Successful treatment of keratosis follicularis squamosa with topical tacalcitol.

PMID- 16634919
TI  - Nonsedating antihistamines in the treatment of severe chronic idiopathic
      urticaria: are they used optimally?

PMID- 16634920
TI  - A case of cutaneous leiomyosarcoma with overexpression of KIT: do CD117 (KIT)
      positive primary gastrointestinal stromal tumours of the skin exist?

PMID- 16634921
TI  - Recent record of the U.K. to publication in top dermatology journals.

PMID- 16634922
TI  - Melanoma in Leicestershire: effect of the 2-week wait system on presentation.

PMID- 16634923
TI  - Intraepidermal neutrophilic IgA/IgG antidesmocollin 1 pemphigus.

PMID- 16634924
TI  - Lichenoid eruption associated with orlistat.

PMID- 16634925
TI  - Extranodal conjunctival Hodgkin's-like lymphoma in a cat.
AB  - A seven-year-old female spayed Domestic Short-haired cat was brought for
      examination following a four-month history of conjunctivitis in the right eye.
      The superior palpebral conjunctiva was diffusely swollen and firm, displacing the
      right globe ventrally and preventing full closure of the eyelids. The right
      popliteal lymph node was enlarged as were several other peripheral lymph nodes.
      An incisional biopsy of the conjunctival swelling revealed a lymphoid neoplasm,
      the cellular make up of which suggested features of feline Hodgkin's-like
      lymphoma. Although the neoplasm was poorly responsive to standard
      chemotherapeutic protocols for lymphoma, radiation therapy rapidly reduced its
      size. Three years following the initial diagnosis, there has been no recurrence
      of the conjunctival neoplasm. To the authors' knowledge, there are no previous
      reports of extranodal or adnexal (conjunctiva, eyelid, orbit) Hodgkin's-like
      lymphoma in the veterinary literature.

PMID- 16634926
TI  - Ocular lesions in Watanabe heritable hyperlipidemic rabbits.
AB  - Hyperlipidemic ocular lesions are described for Watanabe heritable hyperlipidemic
      (WHHL) rabbits. Male WHHL rabbits 8 months old exhibited serum hyperlipidemia and
      ophthalmoscopically yellowish-white lesions along the corneoscleral junction and
      in the iris. Histopathologically, foamy macrophages aggregated in the stroma of
      the cornea, iris, and ciliary body were observed. These findings have been
      interpreted as lipid keratopathy. In addition, multiple clusters of a large
      number of foamy macrophages occurred throughout the choroid and sclera in
      association with the blood vessels. The lesions in the choroid and sclera could
      not be detected ophthalmoscopy, yet were much more prominent than those in the
      cornea, iris, and ciliary body, suggesting greater involvement and earlier onset
      of lipidosis at these sites associated with hyperlipidemia in WHHL rabbits.

PMID- 16634927
TI  - Scleral rupture in dogs, cats, and horses.
AB  - OBJECTIVES: The aim of this retrospective study was to summarize the most
      frequent clinical signs, ultrasonographic, and histological findings accompanying
      scleral rupture as a result of blunt trauma in dogs, cats, and horses. ANIMALS
      STUDIED AND PROCEDURES: Thirty small animals and three horses diagnosed with
      scleral rupture resulting from blunt trauma. B-mode ultrasonography was performed
      on 20 animals. Histopathology was carried out on 18 enucleated globes. RESULTS:
      In small animals, 80% presented hyphema, 60% subconjunctival hemorrhage, and 53%
      eyelid and conjunctival swelling. In horses, 100% presented eyelid and
      conjunctival swelling, 67% hyphema, subconjunctival hemorrhage, and collapsed
      anterior chamber. Ultrasonographic findings were an area with ill-defined scleral
      margins (90%), echoic/hyperechoic contents in the anterior and posterior chamber
      (55%) and in the vitreous (80%). In small animals, scleral rupture location noted
      on gross examination was: at the posterior pole (4), close to the optic nerve
      (3), near the limbus (2), and in the dorsal aspect of the globe (1). In horses,
      the lesion was located at the limbus (3). In small animals, histopathology showed
      presence of hemorrhage in the anterior, posterior chamber, and vitreous (94%),
      retinal detachment (94%), choroidal edema and hemorrhages (88%), and choroidal
      detachment as a result of suprachoroidal hemorrhage (88%). The same lesions were
      found in the globes of two horses. In small animals, rupture location noted on
      histopathology was: at the posterior pole (8), close to the optic nerve (4), near
      the limbus (1), near the ciliary body (1). CONCLUSIONS: The most frequent
      clinical signs observed were hyphema, subconjunctival hemorrhage, and eyelid and
      conjunctival swelling. Ultrasonographic findings suggestive for scleral rupture
      were ill-defined scleral borders and/or echoic/hyperechoic material in the
      cavities of the globe. On histopathology, lesions severely altering the anatomy
      of the eye structures were: hemorrhage into the chambers of the globe, subretinal
      and suprachoroidal hemorrhage leading to retinal and choroidal detachment,
      respectively. In small animals, the most frequent locations for scleral rupture
      were the posterior pole and close to the optic nerve, whereas in horses it was
      the limbus.

PMID- 16634928
TI  - Topical effect of various agents on gelatinase activity in the tear film of
      normal dogs.
AB  - OBJECTIVE: To evaluate the topical effect of various agents, currently used in
      the treatment of melting ulcers, on gelatinase activity present in the tear film
      of normal dogs. ANIMAL STUDIED: Eight normal adult beagles. PROCEDURES: Each
      animal received the following agents: cyclosporine A 1%, N-acetylcysteine 10%,
      ciprofloxacin 0.3%, ethylenediaminetetraacetic acid (EDTA) 1%, doxycycline
      0.001%, polysulfated glycosaminoglycans (PSGAG) 5%, autoserum, and artificial
      tears during a 48-h period following a Latin square design. Tear samples were
      collected with micro-capillary pipettes following a corneal surface irrigation of
      each eye with sterile saline on four different occasions. Basal and total
      gelatinase activities were evaluated by optical density after processing in a
      commercial gelatinase activity assay. From the optical density ratio, a semi
      quantitative measure of gelatinase activity was obtained. Basal and total
      activities were measured in all samples. RESULTS: The lowest total gelatinase
      activity, representing a percent decline in the enzyme activity although not
      significant, was observed 1 h after the last treatment in seven out of the eight
      ophthalmic agents; EDTA (68%), ciprofloxacin (76%), cyclosporine A (68%),
      doxycycline (47%), artificial tears (26%), PSGAG (25%), and N-acetylcysteine
      (20%). However, only the reduction observed with EDTA 6 h after the last
      treatment was significantly lower compared to the reduction observed with the
      artificial tears. CONCLUSION: This study indicated that only EDTA was able to
      significantly reduce the gelatinase activity in a persistent manner in the tear
      film of normal canine eyes. Further studies will be required to evaluate the
      effect of EDTA under ulcerative conditions and to more accurately ascertain the
      potential in vivo effect of the other agents.

PMID- 16634929
TI  - Ophthalmomyiasis interna anterior in a cat: surgical resolution.
AB  - A 4-year-old Domestic short-haired cat was presented for severe anterior uveitis
      in the right eye associated with a Cuterebra spp. larva in the anterior chamber.
      This report describes successful surgical removal of the parasite with
      preservation of vision.

PMID- 16634930
TI  - Leptospirosis and panuveitis in a dog.
AB  - A case of panuveitis as a result of leptospiral infection in an 8-year-old Jack
      Russell Terrier is reported. Mild hyphema, aqueous flare, and partial serous
      retinal detachments were noted in both eyes on initial ophthalmic examination.
      The serum microscopic agglutination testing for Leptospira serovarieties revealed
      titers of 1 : 12 800 for Leptospira canicola and 1 : 200 for Leptospira
      icterohemorrhagiae. With medical therapy, the panuveitis resolved and functional
      vision was regained. Four weeks after the initial presentation, convalescent
      titers were 1 : 200 for L. canicola and 1 : 100 for L. icterohemorrhagiae. The
      incidence of leptospirosis, along with difficulties diagnosing, and current
      medical therapies for this disease are also discussed.

PMID- 16634931
TI  - Primary Aspergillus and Fusarium keratitis in a Holstein cow.
AB  - A 5-year-old female Holstein cow was examined for ocular discharge, periorbital
      swelling, an area of full-thickness corneal cellular infiltrate, fibrin,
      hypopyon, diffuse corneal edema, and miosis. The patient was diagnosed with a
      corneal stromal abscess and secondary anterior uveitis. Histopathology, mycotic
      culture, and polymerase chain reaction positive for Aspergillus and Fusarium DNA
      confirmed the presence of fungal infection. Response to therapy was adequate, and
      follow-up with the patient 1 year after diagnosis revealed a focal area of
      corneal fibrosis.

PMID- 16634932
TI  - Canine limbal melanoma: 30 cases (1992-2004). Part 2. Treatment with lamellar
      resection and adjunctive strontium-90beta plesiotherapy--efficacy and morbidity.
AB  - OBJECTIVES: To evaluate the efficacy of lamellar resection and adjunctive 90Sr
      beta plesiotherapy in the management of canine limbal melanoma and the frequency
      and morbidity of early and late-onset side effects following treatment. DESIGN:
      Retrospective study. ANIMALS STUDIED: Thirty dogs treated for limbal melanoma at
      the Animal Health Trust (AHT), between 1992 and 2004. METHODS: Medical records
      were reviewed and information collected on the radiation dose administered,
      duration of follow-up, and the frequency of early- and late-onset ocular side
      effects. Follow-up information was obtained by re-examination of patients or
      completion of a telephone interview with the referring veterinary surgeons or the
      owners. RESULTS: Recurrence of limbal melanoma occurred in 1 of 30 cases (3%; 95%
      CI: 0.2-14%). One or more side effects occurred in 16 of 30 cases (53%; 95% CI:
      28.1-74.9). The occurrence of side effects was not associated with the number of
      sites treated or the total surface dose of radiation. Short-term side effects
      were reported in 16/30 cases (53%) and included corneal scarring (12/30), corneal
      neovascularization (6/30), conjunctivitis with or without granulation tissue
      formation (5/30), lipid keratopathy (1/30), and localized bullous keratopathy
      (2/30). Long-term side effects were reported in 6 of 30 cases (20%) cases and
      included deep scleral thinning (5/30), focal scleromalacia (3/30), globe
      perforation (2/30), lipid keratopathy (3/30), localized bullous keratopathy
      (1/30), and sectoral cortical cataract (1/30). CONCLUSIONS: Lamellar resection
      and adjunctive 90Sr-beta plesiotherapy is relatively easy to perform, is
      minimally invasive, and extremely well tolerated by patients. The treatment is
      highly efficacious in the management of canine limbal melanoma. Modification of
      the radiation dosimetry, in particular reducing the total dose of radiation and
      the dose per radiation fraction, is necessary to reduce the incidence of late
      onset side effects.

PMID- 16634933
TI  - Calcification associated with the nasolacrimal system of a horse: case report and
      mineralogic composition.
AB  - A 12-year-old Paso Fino mare was evaluated for a chronic nasal and ocular
      discharge. A calcification was identified eroding through the nasal mucosa of the
      middle meatus. Differential considerations for this mass included dacryolith,
      nasal calculus, or calcified tooth root abscess. Anatomical location and case
      history and progression supported a dacryolith. Following removal, the calculus
      was submitted for mineralogic analysis. The calculus was primarily carbonate
      hydroxylapatite (Ca10(PO4)3(CO3)3(OH)2) with a minor NaCl halite constituent.
      Dacryoliths, or nasolacrimal calculi, are an uncommon occurrence in animals, and
      sparsely reported in humans. The etiopathogenesis of dacryolith formation is
      unknown. The objective of this article was to report the first case report of an
      equine nasolacrimal system dacryolith and its mineralogic composition.

PMID- 16634934
TI  - Interspecies variation in orbital bone structure of psittaciform birds (with
      emphasis on Psittacidae).
AB  - OBJECTIVE: This text presents an anatomical study of the normal bony orbital
      structure of a sample of different bird species belonging to the order
      Psittaciformes. PROCEDURES: The bony anatomy of Psittaciformes' skulls was
      examined and described using cadavers of birds that were presented already dead
      to the Federal University of Parana, Brazil or had been euthanized for humane
      reasons. Dissections of the orbital cavity were performed under 2-4 x
      magnification, and descriptions of the orbital bones were made from observations
      of macerated skulls that had been boiled and cleaned. The present paper discusses
      the main features of the bony orbit of psittaciform birds, describing known
      anatomical information but also bringing new information, mainly concerning
      species differences that might help not only veterinary anatomists but also
      zoologists, clinicians, researchers, and students of veterinary ophthalmology to
      better comprehend this order of birds. RESULTS AND CONCLUSIONS: Variations in the
      anatomic conformation of the bony elements of the orbit were observed in
      different species of Psittaciformes. Based on these differences, Psittaciformes
      were classified into two different groups. The first group of Psittaciformes
      shows an enclosed (complete) bony orbit formed by the junction of the orbital
      with the postorbital processes, creating a suborbital arch. The second group of
      Psittaciformes essentially lacked a suborbital arch, presenting an open
      (incomplete) bony orbit, typical of most modern birds. In the latter group,
      orbital and postorbital processes are present.

PMID- 16634935
TI  - Evaluation of canine serum for the presence of antiretinal autoantibodies in
      sudden acquired retinal degeneration syndrome.
AB  - OBJECTIVE: To determine the presence of serum antiretinal antibodies in sudden
      acquired retinal degeneration syndrome (SARDS) affected dogs and the size of the
      antigen to which these antibodies bind via the use of enzyme-linked immunosorbent
      assay (ELISA) and Western blot immunoassays. ANIMALS STUDIED: Serum was collected
      from 13 dogs affected by SARDS and five dogs with normal ocular examinations.
      PROCEDURES: All serum samples were subjected to ELISA with saline-soluble canine
      retinal tissue and Western blot analyses with SDS solubilized normal canine
      retinal tissue as the antigen. Antirecoverin (23 kDa) and antiheat shock cognate
      (65 kDa) antibodies were used as positive controls for both procedures. Affinity
      purified goat antidog IgG and IgM labeled with horseradish peroxidase were used
      for all clinical samples and goat antirabbit IgG was used as the secondary
      antibody for the positive controls. RESULTS: ELISA demonstrated antibody reaction
      with all samples. Western blot immunoassays identified multiple bands in all
      canine serum samples, as well as in negative controls. Approximate sizes of the
      bands were 25 and 50 kDa, corresponding to IgG light and heavy chains,
      respectively. CONCLUSION: No antiretinal autoantibodies were identified in the
      serum of dogs affected by SARDS as compared to normal canine patients.

PMID- 16634936
TI  - Drusen and lipid-filled retinal pigment epithelium cells in a rhesus macula.
AB  - A middle-aged rhesus monkey with detailed clinical history exhibited progression
      of a macular abnormality with a variety of clinical drusen and pigment changes
      typical of the Cayo Santiago phenotype. Numerous frozen sections of one sample of
      the macular retina/retinal pigment epithelium (RPE)/choroid showed a single
      classical druse but extensive single and clustered lipid-filled RPE cells. The
      monkey exhibited functional outer retinal decline and an insignificant number of
      'window defects' as found among signs of relatively benign human macular aging.
      The clinical and histologically defined results agree if lipid-filled RPE cells
      are included among the clinically apparent signs of drusen.

PMID- 16634938
TI  - Plagiarism--does the punishment fit the crime?

PMID- 16634939
TI  - Clinical evaluation of intranasal benzodiazepines, alpha-agonists and their
      antagonists in canaries.
AB  - OBJECTIVE: To evaluate the effects of intranasal benzodiazepines (midazolam and
      diazepam), alpha(2)-agonists (xylazine and detomidine) and their antagonists
      (flumazenil and yohimbine) in canaries. STUDY DESIGN: Prospective randomized
      study. ANIMALS: Twenty-six healthy adult domesticated canaries of both sexes,
      weighing 18.3 +/- 1.0 g. METHODS: In Study 1 an attempt was made to determine the
      dose of each drug that allowed treated canaries to be laid in dorsal recumbency
      for at least 5 minutes, i.e. its effective dose. This involved the evaluation of
      various doses, during which equal volumes of the tested drug were administered
      slowly into each nostril. In study 2 the onset of action, duration and quality of
      sedation induced by each drug at its effective dose were evaluated. The efficacy
      of flumazenil and yohimbine in antagonizing the effects of the sedative drugs was
      also studied. RESULTS: In study 1 administration of 25 microL per nostril
      diazepam (5 mg mL(-1) solution) or midazolam (5 mg mL(-1) solution) to each bird
      caused adequate sedation within 1-2 minutes; birds did not move when placed in
      dorsal recumbency. After administration of 12 microL per nostril of either
      xylazine (20 mg mL(-1)) or detomidine (10 mg mL(-1)), birds seemed heavily
      sedated and assumed sternal recumbency but could not be placed in dorsal
      recumbency. Higher doses of xylazine (0.5 mg per nostril) or detomidine (0.25 mg
      per nostril) prolonged sedation but did not produce dorsal recumbency. In study 2
      in all treatment groups, onset of action was rapid. Duration of dorsal recumbency
      was significantly longer (p < 0.05) with diazepam (38.4 +/- 10.5 minutes) than
      midazolam (17.1 +/- 2.2 minutes). Intranasal flumazenil (2.5 microg per nostril)
      significantly reduced recumbency time. Duration of sedation was longer with
      alpha(2)-agonists compared with benzodiazepines. Detomidine had the longest
      duration of effect (257.5 +/- 1.5 minutes) and midazolam the shortest (36.9 +/-
      2.4 minutes). Nasally administered flumazenil significantly reduced the duration
      of sedation with diazepam and midazolam while yohimbine (120 microg per nostril)
      effectively antagonized the effects of xylazine and detomidine. CONCLUSION:
      Intranasal benzodiazepines produce rapid and effective sedation in canaries.
      Intranasal alpha(2) agonists produce sedation but not sustained recumbency.
      Specific antagonists are also effective when used by this route. Clinical
      relevance Intranasal sedative drug administration is an acceptable alternative
      method of drug delivery in canaries.

PMID- 16634940
TI  - The effect of hyoscine on dobutamine requirement in spontaneously breathing
      horses anaesthetized with halothane.
AB  - OBJECTIVE: To determine whether hyoscine has a sparing effect on the volume of
      dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses
      anaesthetized with halothane. STUDY DESIGN: Prospective, randomized, controlled
      clinical trial. ANIMALS: Twenty adult horses weighing 507 +/- 97 kg (mean +/-
      SD), aged 10 +/- 5 years. MATERIALS AND METHODS: Pre-anaesthetic medication in
      all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous
      (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg
      kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothane in
      oxygen. Horses breathed spontaneously. Flunixin (1.1 mg kg(-1) IV) was given to
      provide analgesia. Heart rate, ECG, invasive arterial pressure, respiratory rate,
      percentage end-tidal carbon dioxide, percentage end-tidal halothane and partial
      pressure of oxygen and carbon dioxide in arterial blood and blood pH were
      monitored. Dobutamine was infused by an infusion pump to maintain MAP at 70 mmHg.
      Horses were randomly assigned to receive saline or hyoscine (0.1 mg kg(-1)) IV 30
      minutes after induction. The heart rate, MAP and volume of dobutamine infused
      over 30-minute periods were measured and analysed statistically using a one-way
      anova. RESULTS: After administration of hyoscine, heart rate increased for 10
      minutes (p < 0.01) and MAP for 5 minutes (p < 0.01). There was no difference in
      the volume of dobutamine infused over 30 minutes between horses given hyoscine or
      saline, although there was a wide individual variation in dobutamine
      requirements. No side effects of hyoscine were seen. CONCLUSIONS: The increase in
      heart rate and blood pressure that occurs after 0.1 mg kg(-1) hyoscine is given
      IV in anaesthetized horses, is of short duration and does not significantly alter
      the amount of dobutamine required to maintain arterial pressure over the next 30
      minutes. Clinical relevance The short duration of action of 0.1 mg kg(-1)
      hyoscine IV may limit its usefulness for correction of hypotension in horses
      anaesthetized with halothane. Further work is necessary to investigate the
      effects of higher or repeated doses or constant rate infusions of hyoscine.

PMID- 16634941
TI  - A comparison of cardiorespiratory variables during isoflurane-fentanyl and
      propofol-fentanyl anaesthesia for surgery in injured cats.
AB  - OBJECTIVE: To compare haemodynamic and respiratory variables during isoflurane
      fentanyl (IF) and propofol-fentanyl (PF) anaesthesia for surgery in injured cats.
      STUDY DESIGN: Prospective, randomized, controlled clinical study. ANIMALS: Thirty
      three client-owned injured cats undergoing orthopaedic surgery. MATERIALS AND
      METHODS: Pre-anaesthetic medication was intravenous midazolam 1 mg kg(-1),
      butorphanol 0.4 mg kg(-1) and ketamine 2 mg kg(-1). Anaesthesia was induced with
      propofol (P) and maintained with either: (a) a continuous rate infusion (CRI) of
      fentanyl (F) 0.02 mg kg(-1) hour(-1) and isoflurane (initial end-tidal
      concentration of 1%), (b) a fentanyl CRI (dose as before) and sevoflurane
      (initial end-tidal concentration of 2%) or (c) a CRI of propofol (12 mg kg(-1)
      hour(-1)). All three techniques were given to effect until surgical anaesthesia
      was achieved. Heart rate and rhythm (ECG), mean arterial blood pressure,
      respiratory rate, tidal volume and end-tidal CO(2) concentration were recorded.
      Venous blood gas analysis was performed before and after sedation, and at the end
      of anaesthesia. Blood chemistry and blood cell counts were assessed before, at
      the end of, and 24 hours after anaesthesia. The variables recorded from cats
      anaesthetized with IF and PF were compared. RESULTS: Mean end-expiratory
      isoflurane concentration was 1.19 +/- 0.19%. The propofol infusion rate was 11.4
      +/- 0.8 mg kg(-1) hour(-1). No significant differences between the two groups in
      heart rate were identified; no cardiac dysrhythmias were recorded. Mean arterial
      blood pressure was significantly lower in IF cats during skin incision (p =
      0.01), during surgery without intense surgical stimulation (p < 0.01) and during
      surgery with intense surgical stimulation (p = 0.01). Nine of 11 cats in the IF
      group were markedly hypotensive (34-49 mmHg) while seven of 11 cats in group PF
      were mildly hypotensive (49-59 mmHg). One of 11 cats in group IF and nine of 11
      cats in group PF required intermittent positive pressure ventilation (IPPV) to
      maintain end-tidal CO(2) levels below 6.66 kPa (50 mmHg). CONCLUSION AND CLINICAL
      RELEVANCE: Despite the necessity to ventilate the lungs of cats in the PF group,
      arterial blood pressure was better maintained. Propofol-fentanyl anaesthesia is
      better for surgery in injured cats providing the means to impose IPPV are
      available.

PMID- 16634942
TI  - The effects of propofol, isoflurane and sevoflurane on vecuronium infusion rates
      for surgical muscle relaxation in dogs.
AB  - OBJECTIVE: To compare the constant rate infusion (CRI) of vecuronium required to
      maintain a level of neuromuscular blockade adequate for major surgeries, e.g.
      thoracotomy or laparotomy, in dogs anaesthetized with a CRI of fentanyl and
      either propofol, isoflurane or sevoflurane. STUDY DESIGN: Prospective,
      randomized, cross-over study. ANIMALS: Thirteen male beagles (age, 9-22 months;
      body mass 6.3-11.3 kg). MATERIALS AND METHODS: Dogs were anaesthetized with
      propofol (24 mg kg(-1) hour(-1) IV CRI; group P), isoflurane (1.3% end-tidal
      concentration; group I) or sevoflurane (2.3% end-tidal concentration; group S)
      with fentanyl (5 microg kg(-1) hour(-1) IV, CRI). Sixty to seventy minutes after
      induction of anaesthesia, vecuronium was administered at a rate of 0.4, 0.3 and
      0.2 mg kg(-1) hour(-1) in groups P, I and S respectively. To determine the degree
      of neuromuscular block, a peripheral nerve was stimulated electrically using the
      train-of-four (TO4) stimulus pattern. Evoked muscle contractions were evaluated
      using a neuromuscular monitoring device. Once the TO4 ratio reached 0, the
      continuous infusion rate was decreased and adjusted to maintain a TO4 count of 1.
      Continuous infusion was continued for 2 hours. The infusion rate of vecuronium
      was recorded 20, 40, 60, 80, 100 and 120 minutes after the start of infusion.
      RESULTS: The mean continuous infusion rates of vecuronium during stable infusion
      were 0.22 +/- 0.04 (mean +/- SD), 0.10 +/- 0.02 and 0.09 +/- 0.02 mg kg(-1) hour(
      1) in groups P, I and S respectively. There were statistically significant
      differences between the rates in groups P and I and between the rates in groups P
      and S. Conclusions and clinical relevance In healthy dogs, the recommended
      maintenance infusion rate of vecuronium is 0.2 mg kg(-1) hour(-1) under CRI
      propofol-fentanyl anaesthesia and 0.1 mg kg(-1) hour(-1) during CRI fentanyl
      isoflurane or sevoflurane anaesthesia.

PMID- 16634943
TI  - Successful resuscitation from cardiac arrest associated with extradural lidocaine
      in a dog.
AB  - BACKGROUND: Extradural lidocaine exerts several adverse effects which are seldom
      fatal. While cardiac arrest following extradural lidocaine injection has been
      reported in human beings, it has not hitherto been reported in dogs.
      OBSERVATIONS: The emergency management of a dog with complete urethral
      obstruction is described. We intended to perform vaginoscopy and cystostomy under
      extradural lidocaine anaesthesia, but cardiac asystole occurred a few minutes
      after injection. Resuscitation was successful. About 20 minutes later cardiac
      arrest recurred, and was treated successfully. The dog remained hypothermic for
      approximately 7 hours. Complete recovery without neurological deficit occurred
      the next day and the dog remained normal for at least 3 months. The probable
      cause of the problem was cranial lidocaine dispersion causing a drop in cardiac
      preload and cardiac arrest. The successful neurological outcome was attributed to
      early diagnosis and effective treatment. Hypothermia may have conferred cerebral
      protection during ischemia. CONCLUSIONS: Extradural local anaesthetic
      administration is not without risk and the technique should be tailored to
      individual animals. Constant monitoring is required to detect potentially fatal
      complications and increase the likelihood of successful outcome.

PMID- 16634944
TI  - Morphine administration in horses anaesthetized for upper respiratory tract
      surgery.
AB  - OBJECTIVE: To determine the effect of morphine administration on commonly
      monitored cardio-respiratory variables and recovery quality in horses undergoing
      anaesthesia and surgery. STUDY DESIGN: Prospective, randomized clinical study.
      ANIMALS: Thirty-eight thoroughbred horses, 32 geldings and six mares, 3-13 years
      old, weighing 411-600 kg. MATERIALS AND METHODS: A standard anaesthetic technique
      was used. Twenty minutes after induction of anaesthesia horses received 0.1 mg
      kg(-1) (0.1 m) or 0.2 mg kg(-1) (0.2 m) morphine by intravenous injection. A
      control group did not receive morphine. Heart rate, respiratory rate (fr), mean
      arterial pressure (MAP) and blood gases were measured before morphine
      administration and every 10 minutes thereafter. Horses were positioned for 35
      minutes in right lateral recumbency for tension palatoplasty by cautery and were
      then moved into dorsal recumbency for additional intraluminal surgery comprising
      one or more of aryepiglottic fold resection, sub-epiglottal mucosal resection,
      ventriculectomy and cordectomy. A subjective recovery score from 0 (worst) to 5
      (best) was assigned by a single observer who was unaware of treatment group. Two
      way repeated measures anova, one-way anova, Kruskal-Wallis test, Mann-Whitney
      test, Pearson and Spearman correlation coefficients, and chi-squared tests were
      used to analyse the data where appropriate. RESULTS: Arterial partial pressure of
      oxygen (PaO(2)) decreased significantly over time and was significantly lower in
      horses that received morphine. One horse in the control group and two horses in
      each of the morphine groups had a PaO(2) <13 kPa. No other significant
      cardiopulmonary effects were detected. Recovery scores [median (range)] were
      higher in morphine recipients: 4 (2-5) in 0.1 m, 4 (3-5) in 0.2 m compared with 3
      (2-4) in the control group. CONCLUSIONS AND CLINICAL RELEVANCE: The lower PaO(2)
      in morphine recipients did not appear to be of clinical significance in healthy
      horses because the number of horses with a low PaO(2) was similar between groups.
      The quality of recovery was significantly better in morphine recipients. These
      results indicate that morphine may be considered for use in clinical cases
      although further work is required to assess the analgesic properties of the drug
      in this species.

PMID- 16634945
TI  - Continuous extradural analgesia in a cow with complex regional pain syndrome.
AB  - A chronic pain syndrome, similar to the complex regional pain syndrome (CRPS)
      described in human beings, was diagnosed in a cow with persisting severe pelvic
      limb lameness. Diagnosis was based on the disproportionate relationship between
      the severity and duration of pain and the lesion, the failure of conventional
      analgesic and surgical therapy and the presence of characteristic clinical
      features. Multimodal therapy, i.e. a mixture of methadone, ketamine and
      bupivacaine was administered continuously for 17 days via an extradural catheter
      to counteract nociceptive hypersensitization. Doses were adjusted daily after
      assessing the effect, using a composite pain score. Physiotherapy was also
      performed. The diagnosis of CRPS in cattle is unusual. In this case, treatment
      was successful and the cow was discharged mildly lame and in improving physical
      condition. Long-term extradural analgesia proved to be safe and effective in the
      treatment of this syndrome, which was nonresponsive to conventional therapy.

PMID- 16634946
TI  - Morphine-associated pruritus after single extradural administration in a horse.
AB  - Pruritus following a single administration of 100 microg kg(-1) of preservative
      free morphine sulphate given via an extradural catheter was seen in a 580 kg
      horse. The catheter was placed in the first intercoccygeal space. Focal
      irritation, represented by both local alopecia over the left gluteal muscles and
      serum exudation, occurred 4-8 hours after injection. This was attributed to the
      extradural morphine administration.

PMID- 16634949
TI  - Nutrition and inflammation: the missing link between periodontal disease and
      systemic health in the frail elderly?

PMID- 16634950
TI  - Association between serum albumin and periodontal disease in community-dwelling
      elderly.
AB  - AIM: The purpose of this study was to evaluate the relationship between
      periodontal disease and general health status in community-dwelling elderly using
      serum albumin concentration as a criterion index of the severity of an underlying
      disease and nutrition status. METHODS: Serum albumin level was detected by the
      bromcresol green albumin (BCG) method and the data for serum albumin were
      available in 368 subjects aged 75 years. Pressure-sensitive probes were used to
      measure loss of attachment (LA) on six sites of all teeth present. Information
      relevant to gender and smoking habit was obtained by means of a personal
      interview, while body mass index (BMI) and biochemical serum markers were
      investigated. RESULTS: Serum albumin concentration ranged from 3.2 to 4.8 g/dl
      with a mean of 4.1+/-0.2. More than 70% of subjects had at least one site with LA
      6+ mm, while 91 exhibited 10% or more sites with LA 6+ mm. Using a multiple
      regression analysis, we found that sites of LA 6+ mm had a significant effect on
      serum albumin level (correlation coefficient=-0.14; p<0.05), which was
      independent of the other covariates. CONCLUSIONS: The findings of the present
      study indicated that there might be an inverse relationship between periodontal
      disease and serum albumin concentration in these elderly subjects.

PMID- 16634951
TI  - Is there a relationship between juvenile idiopathic arthritis and periodontitis?
AB  - AIM: The aim was to compare the prevalence of periodontal conditions in patients
      with juvenile idiopathic arthritis (JIA) (n=78, age 14.4 years) with those
      revealed in a healthy control group (n=75, age 15.5 years). MATERIAL AND METHODS:
      In both groups, the approximal plaque index (API), the modified sulcular bleeding
      index (SBI), and the clinical attachment loss (CAL) were determined. Laboratory
      parameters for JIA activity included the capsule-reactive protein (CRP) and the
      immunoglobulins A, G, M. RESULTS: JIA patients had a significantly higher API
      (64.6%versus 49.9%, p=0.004) and slightly higher mean percentages of sites with
      CAL>3.5 mm (0.58%versus 0.22%, p=0.041). There was no significant difference in
      the prevalence of patients and controls who had sites with CAL >3.5 mm
      (25.6%versus 17.3%, p=0.212). The mean CAL was slightly greater (0.2 mm; p=0.030)
      in patients with CRP> or =5.0 mg/l compared with patients with CRP<5.0 mg/l.
      Patients who took non-steroidal anti-inflammatory drugs (NSAIDs) had a
      significantly decreased SBI (26.2%versus 51.1%, p=0.019). CONCLUSION: After
      adjustment for microbial plaque, JIA is not a risk factor for periodontitis.

PMID- 16634952
TI  - Time as a factor in the identification of subjects with different susceptibility
      to plaque-induced gingivitis.
AB  - OBJECTIVES: The purpose of this study was to assess whether identification of
      subjects with different susceptibility to plaque-induced gingival inflammation is
      dependent on the length of time of de novo plaque accumulation. METHODS:
      Retrospective analysis of data obtained from a recently reported randomized split
      mouth localized experimental gingivitis trial involving 96 healthy non-smokers.
      Gingival and plaque index, gingival crevicular fluid volume (GCF), angulated
      bleeding score, and the derived parameter cumulative plaque exposure (CPE) were
      recorded at days 0, 7, 14, and 21. The primary outcome variable to express
      severity of inflammation was GCF and each subject was a statistical unit. Based
      on subject distribution of GCF-day 21 residuals after standardization for CPE-day
      21, two sub-populations (upper and lower distribution quartiles) were selected.
      They were, respectively, defined as "high responders" (HR) (n=24) and "low
      responders" (LR) (n=24) and characterized by significantly different severity of
      gingivitis to similar amounts of plaque deposits. The same analysis was repeated
      at days 7 and 14. Prevalence of HR and LR was compared between days using the
      chi(2) [ML] test. RESULTS: For both day 7 and day 14, the quartile distribution
      of LR and HR was statistically significant (p=0.02). Fifty percent of LR and 71%
      of HR presented a consistent level of susceptibility to plaque-induced gingival
      inflammation even after only 7 and/or 14 days of plaque accumulation.
      CONCLUSIONS: These findings support the concept that the subject-based
      susceptibility to plaque-induced gingival inflammation is an individual trait,
      only partly related to the length of time of exposure to plaque.

PMID- 16634953
TI  - Persistence of Helicobacter pylori in the oral cavity after systemic eradication
      therapy.
AB  - AIM: The present study aimed to evaluate if the oral cavity of chronic
      periodontitis patients can harbor Helicobacter pylori after systemic eradication
      therapy. MATERIALS AND METHODS: Samples of 30 patients (15 with gingivitis and 15
      with chronic periodontitis) positive for H. pylori in the stomach were evaluated.
      Samples were collected 3 months after triple systemic antibiotic therapy from
      saliva, microbiota from the dorsum of the tongue, supra- and sub-gingival plaque
      as well as gastric biopsies. DNA of each sample was extracted by the boiling
      method and used as a template in polymerase chain reaction with the primers
      JW22/23. RESULTS: Eighteen patients (60%) harboured H. pylori in their mouths.
      Five patients (16.6%) were positive in saliva, two (6.6%) on the dorsum of the
      tongue, nine (30%) in supra-gingival plaque, 14 (46.6%) in sub-gingival plaque
      and three (10%) in the stomach. There was no statistically significant difference
      between study groups. CONCLUSION: Eradication of H. pylori after therapy was more
      effective for the stomach than for the mouth (p<0.001). Mouths of patients with
      gingivitis or with chronic periodontitis, who are positive for H. pylori in their
      stomachs, may be considered as reservoirs of these bacteria.

PMID- 16634954
TI  - Differences in efficacy of two commercial 0.2% chlorhexidine mouthrinse
      solutions: a 4-day plaque re-growth study.
AB  - BACKGROUND: The purpose of this clinical cross-over study was to examine the
      antibacterial and plaque-inhibiting properties of two chlorhexidine solutions
      compared with a negative control. MATERIAL AND METHODS: Twenty-one volunteers
      refrained from all oral hygiene measures, but rinsed instead twice daily with 10
      ml of a conventional chlorhexidine solution (0.2%; CHX), a chlorhexidine solution
      with anti-discolouration system (ADS) (0.2%, alcohol-free chlorhexidine solution
      (CSP)) or a placebo solution (Pla). Plaque index (PI), plaque area (PA) and
      bacterial vitality were assessed after 24 h (PI1, vital flora (VF)1) and 96 h
      (PI2; VF2, PA). After a 10-day wash-out period, a new test cycle was started.
      RESULTS: Results for Pla were 0.94, 1.59, 27.4 (PI1, PI2, PA) and 79% and 72%
      (VF1 and VF2). CSP significantly reduced the parameter PI1, PI2 and PA to 0.67
      (p=0.012), 1.0 and 15.7 (p<0.001). VF1 and VF2 (63% and 53%) were not
      significantly affected. The corresponding figures of CHX were 0.42, 0.43, 6.77,
      33 and 16%, which were all significantly lower (all p<0.001). On comparing the
      two chlorhexidine solutions, CHX showed significantly higher reductions of all
      parameters. CONCLUSION: The results suggest that the 0.2% alcohol-containing
      solution showed superiority in inhibiting plaque re-growth and reducing bacterial
      vitality compared with the solution with ADS.

PMID- 16634955
TI  - Chlorhexidine mouthrinse in combination with an SLS-containing dentifrice and a
      dentifrice slurry.
AB  - OBJECTIVES: The aim of the present study was to compare the plaque-inhibitory
      effect of a 0.2% chlorhexidine digluconate (CHX) rinse when preceded by ordinary
      toothbrushing with a 1.5% sodium lauryl sulphate (SLS)-containing dentifrice to
      the effect of the same rinse when used alone, or when preceded by rinsing with an
      SLS-containing slurry. METHODS: The study was an examiner blinded, randomized
      three-arm, parallel design. It used a 4-day plaque accumulation model to compare
      three different oral hygiene regimens, which were performed under supervision.
      One hundred and twenty healthy volunteers were enrolled in the study and were
      randomly assigned to one of each group. At the beginning of each test period,
      they received a thorough dental prophylaxis. The experiment was performed in one
      randomly assigned (upper or lower) jaw, called the study jaw. The opposite jaw,
      referred to as the dentifrice jaw, served only to introduce the influence of
      toothbrushing with a dentifrice on the anti-plaque efficacy of the CHX in the
      study jaw of the same mouth. At the end of the 4-day test period, plaque and
      gingival bleeding were scored in the study jaw. In all the regimens, the oral
      hygiene procedure was finalized by rinsing with a CHX 0.2% solution for 1 min.
      The study jaw was not brushed during the experiment. Regimen A (positive control)
      consisted of rinsing with CHX alone. In regimen B, rinsing with CHX was preceded
      by rinsing with an SLS-containing slurry, while in regimen C rinsing with CHX was
      preceded by toothbrushing with an SLS-containing dentifrice in the dentifrice
      jaw. No other oral hygiene measures were allowed. After 4 days of undisturbed
      plaque accumulation, the amount of plaque and level of gingival health were
      evaluated. RESULTS: The overall plaque index for regimens A, B and C was 1.17,
      1.62, and 1.14, respectively. There was no significant difference in plaque
      accumulation between the CHX alone regimen (A) and the SLS-dentifrice-CHX regimen
      (C). Regimen B differed significantly from regimens A and C. The overall bleeding
      index for regimens A, B and C was 0.24, 0.18, and 0.20, respectively. There was
      no significant difference between the three regimens. CONCLUSIONS: The present
      study shows that the anti-plaque efficacy of a 0.2% CHX rinse was not reduced
      when preceded by everyday toothbrushing with a SLS-containing dentifrice.
      However, when preceded by rinsing with an SLS-containing slurry, the anti-plaque
      efficacy of a 0.2% CHX rinse was reduced.

PMID- 16634956
TI  - Ibuprofen arginine for pain control during scaling and root planing: a
      randomized, triple-blind trial.
AB  - OBJECTIVES: The aim of this controlled clinical trial was to investigate the
      analgesic efficacy and tolerability of ibuprofen arginine in patients with mild
      to-moderate periodontitis during and after non-surgical periodontal treatment.
      METHODS: This randomized, triple-blind, placebo-controlled, parallel-group trial
      assessed the analgesic efficacy of ibuprofen arginine (Spedifen) in patients
      undergoing routine periodontal scaling and root planing. 64 patients with chronic
      periodontitis received either 800 mg ibuprofen arginine or placebo 30 min. before
      treatment. Numeric pain and electronic visual analogue scales ranging from 0 to
      100 were used. RESULTS: The average pain levels during treatment were lower
      following ibuprofen arginine (quartiles: 0.5, 4.5, 11) compared with placebo (4,
      16, 26), corresponding to a percentage reduction in median pain of 72% (p=0.023).
      The median maximum pain was 28 (inter-quartile range 10-50) following placebo and
      10 (4-31) following ibuprofen arginine (p=0.065). CONCLUSIONS: In patients with
      mild-to-moderate chronic periodontitis, ibuprofen arginine was safe and superior
      to placebo for alleviating pain during non-surgical periodontal treatment. Its
      painless administration and rapid onset of action make it well suitable for pain
      management in a general dental office.

PMID- 16634957
TI  - Guided tissue regeneration/deproteinized bovine bone mineral or papilla
      preservation flaps alone for treatment of intrabony defects. II: radiographic
      predictors and outcomes.
AB  - OBJECTIVES: This study reports the secondary analysis of a randomized-controlled
      clinical trial designed to assess the efficacy of deproteinized bovine mineral
      and a collagen membrane in the treatment of intrabony defects. The specific aims
      of this report are (1) to analyse the radiographic bone changes 1 year after
      therapy and (2) to assess the association between radiographic defect angle and
      treatment outcomes. MATERIALS AND METHODS: Baseline and 12-month radiographs were
      collected from 120 patients with advanced chronic periodontitis from 10 centres
      in seven countries as part of a multi-centre clinical trial. All patients had at
      least one intrabony defect > or =3 mm in depth. The treatment consisted of
      simplified or modified papilla preservation flaps to access the defect. After
      debridement of the area, a deproteinized bovine mineral and a collagen membrane
      were applied in the test subjects, and omitted in the controls. Main outcome
      measures were radiographic bone fill and defect resolution 1 year after surgery.
      RESULTS: One hundred and twenty pairs of radiographs were obtained, of which 110
      pairs were measurable (57 tests and 53 controls). One year after treatment,
      radiographic resolution of the intrabony component was significantly higher in
      the test group (3.2+/-1.7 mm) when compared with the controls (1.7+/-1.9 mm).
      Multivariate analysis indicated that the treatment and the baseline radiographic
      depth of the intrabony defect significantly influenced the radiographic bone fill
      of the intrabony defect 1 year following treatment. The percentage of resolution
      of the defect was influenced by the treatment provided and the baseline plaque
      score. The baseline radiographic defect angle did not show a significant impact
      on the clinical and radiographic outcomes. CONCLUSIONS: Regenerative periodontal
      surgery with a deproteinized bovine bone mineral and a collagen membrane offered
      additional benefits in terms of radiographic resolution of the intrabony defect
      and predictability of outcomes with respect to papilla preservation flaps alone.

PMID- 16634958
TI  - Systemic antibiotics: to use or not to use in the treatment of periodontal
      infections. That is the question.

PMID- 16634959
TI  - Topical minocycline microspheres versus topical chlorhexidine gel as an adjunct
      to mechanical debridement of incipient peri-implant infections: a randomized
      clinical trial.
AB  - AIM: This randomized clinical trial presents a 12-month follow-up of the clinical
      and microbiological results after application of minocycline microspheres as an
      adjunct to mechanical treatment of incipient peri-implant infections compared
      with an adjunctive treatment using 1% chlorhexidine gel application. MATERIAL AND
      METHODS: Thirty-two subjects with probing depth > or =4 mm, combined with
      bleeding and/or exudate on probing and presence of putative pathogenic bacteria
      were given oral hygiene instructions and mechanical treatment of infected areas
      adjacent to implants. The subjects were then randomly assigned adjunctive
      subgingival antimicrobial treatment using either chlorhexidine gel or minocycline
      microspheres. Sixteen patients in the minocycline group and 14 in the
      chlorhexidine group completed the study. Follow-up examinations were carried out
      after 10 days, 1, 2, 3, 6, 9 and 12 months. RESULTS: The adjunctive use of
      minocycline microspheres resulted in improvements of probing depths and bleeding
      scores, whereas the adjunctive use of chlorhexidine only resulted in limited
      reduction of bleeding scores. For the deepest sites of the treated implants in
      the minocycline group, the mean probing depth was reduced from 5.0 to 4.4 mm at
      12 months. This study could not show any significant difference in the levels of
      bacterial species or groups at any time point between the two antimicrobial
      agents tested. The present findings encourage further studies on adjunctive use
      of minocycline microspheres in the treatment of peri-implant lesions.
      CONCLUSIONS: The use of a local antibiotic as an adjunct to mechanical treatment
      of incipient peri-implantitis lesions demonstrated improvements in probing depths
      that were sustained over 12 months.

PMID- 16634961
TI  - RET receptor signaling: dysfunction in thyroid cancer and Hirschsprung's disease.
AB  - Gain-of-function mutations within the receptor tyrosine kinase gene RET cause
      inherited and non-inherited thyroid cancer. Somatic gene rearrangements of RET
      have been found in papillary thyroid carcinoma and germline point mutations in
      multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid
      carcinoma (FMTC). Conversely, loss-of-function mutations are responsible for the
      development of Hirschsprung's disease, a congenital malformation of the enteric
      nervous system. Comparison between normal RET signaling activated by the RET
      ligand glial cell line-derived neurotrophic factor (GDNF) and abnormal RET
      signaling caused by various mutations has led to a deeper understanding of
      disease mechanisms. The focus of the present review is on recent progress in the
      study of RET signaling dysfunction in human diseases.

PMID- 16634962
TI  - Different types of neural cell death in the cerebellum of the ataxia and male
      sterility (AMS) mutant mouse.
AB  - To investigate the mechanisms(s) of age-dependent atrophy of the cerebellum of
      the ataxia and male sterility (AMS) mouse at young age, the morphological changes
      were evaluated and the nature of neural cell death was examined. Dying Purkinje
      cells lacked characters of classical apoptosis except for light microscopic
      morphology, but their death was considered to be autonomous death triggered by
      the direct effect of ams mutation, because of the acute and near-complete
      disappearance and particular change of the cytoplasm. In contrast, in the
      granular layer, typical apoptotic bodies were recognized by electron microscopy,
      and substantial numbers of terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end-labeling (TUNEL)-positive cells and activated
      caspase-3-positive cells were observed. Granule cell death was considered to be
      target-related apoptosis induced after post-synaptic Purkinje cell death, because
      the age-dependent changes in TUNEL-positive cell counts followed that of Purkinje
      cell loss and the peak value was still noted 1 week after total loss of Purkinje
      cells. These results indicate that both total and partial losses of Purkinje
      cells and granule cells, respectively, contributed to the atrophy of the AMS
      cerebellum. Furthermore, different types of neuronal death were recognized; the
      granule cell death was apoptotic while Purkinje cell death was different from
      that of classical apoptosis.

PMID- 16634963
TI  - Downregulation of a pathogenic autoantibody response by IgM autoantibodies
      directed against the nephritogenic antigen in slowly progressive Heymann
      nephritis.
AB  - The purpose of the study was to find out if a new modified vaccination technique
      would be effective in downregulating immunopathological events during the course
      of an experimental autoimmune kidney disease (which is morphologically and
      functionally similar to Heymann nephritis) called 'slowly progressive Heymann
      nephritis' (SPHN). We have shown that the pathogenic IgG autoantibody (aab)
      induced experimental autoimmune kidney disease process can be downregulated early
      on as well as during the chronic progressive phase, when rats were restimulated.
      The IgM aab, resulting from stimulation by immune complexes made up of rat kidney
      fraction 3 (rKF3) antigen and rat anti-rKF3 IgM antibody in antigen excess (MIC),
      can greatly diminish pathogenic aab production by removing or blocking
      nephritogenic antigens. Reduced IgG aab production limits the formation of
      damaging immune complexes (IC) in the glomeruli and development of proteinuria.
      At the end of the experiment 60% and 80% of the MIC-treated groups had no
      pathogenic IgG aab in their circulation, while all the untreated SPHN rats had
      high levels of IgG aab associated with disease progression manifesting in
      increased proteinuria and severe immune complex glomerulonephritis.

PMID- 16634964
TI  - Histological and cytogenetic characterization of bone marrow in relation to
      prognosis and diagnosis of myelodysplastic syndromes.
AB  - Bone marrow (BM) histology of 102 myelodysplastic syndromes (MDS) patients was
      analyzed retrospectively. All the cases were reclassified according to the World
      Health Organization (WHO) classification. Karyotype study was conducted for all
      except one. Fifteen of the MDS cases were hypoplastic. The cellularity in bone
      marrow histology is sometimes ineffective in the differential diagnosis of MDS
      and aplastic anemia (AA). Nonetheless, a marked decrease in the number of
      megakaryocytes (average, 0.3/mm(2); range, 0-2/mm(2)) even in the hyperplastic
      foci of the marrow of AA was the most important histological feature
      differentiating AA from MDS, whereas the number of megakaryocytes increased in
      most MDS cases (44/mm(2); range, 1-240/mm(2)) and also in hypoplastic MDS
      (14/mm(2); range, 8-26/mm(2)). Hyperplastic marrow had a significantly high
      frequency of progress to acute myeloid leukemia (AML) and hypoplastic MDS had a
      lower rate of progress to AML. Severe myelofibrosis had a significantly poor
      prognosis. An increase in CD34-positive cells in MDS indicated a high rate of
      progress to AML. As for the patients with refractory cytopenia with multilineage
      dysplasia (RCMD; the new category under the WHO classification), the increased
      number of megakaryocytes was correlated with poor prognosis.

PMID- 16634966
TI  - Retraction. Survey of diagnostic accuracy in the College of American
      Pathologists' Performance Improving Program (1993-2003).

PMID- 16634965
TI  - Molecular characteristics of differentiated-type gastric carcinoma with distinct
      mucin phenotype: LI-cadherin is associated with intestinal phenotype.
AB  - Gastric carcinomas (GC) are classified into four phenotypes on the basis of the
      mucin expression profile: G type (gastric or foveolar phenotype), I type
      (intestinal phenotype), GI type (intestinal and gastric mixed phenotype) and N
      type (neither gastric nor intestinal phenotype). Immunohistochemistry was used to
      examine the expression of epidermal growth factor receptor (EGFR), E-cadherin,
      liver-intestine (LI)-cadherin, CD44v9 and p53 and correlation of these molecules
      with mucin phenotype and tumor stage was evaluated. Overexpression of EGFR and LI
      cadherin, reduced expression of E-cadherin and abnormal expression of p53 were
      observed more frequently in advanced GC than in early GC. Among I-type GC,
      overexpression of EGFR and reduced expression of E-cadherin were observed more
      frequently in advanced tumors than in early tumors. Among G-type GC, reduced
      expression of E-cadherin was significantly associated with advanced tumors. With
      respect to the relationship between mucin phenotype and expression of cancer
      related molecules, overexpression of LI-cadherin was observed more frequently in
      I-type (12/25, 48.0%) than in G-type (1/14, 7.1%) GC. I-type GC tended to express
      LI-cadherin more frequently than GI-type GC. These results provide insights into
      the molecular characteristics of the distinct mucin phenotype of differentiated
      type GC and suggest that LI-cadherin may contribute to the biological behavior of
      I-type GC.

PMID- 16634967
TI  - Myoepithelial carcinoma arising in an adenomyoepithelioma of the breast: case
      report with immunohistochemical and mutational analysis.
AB  - Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by
      biphasic proliferation of both epithelial and myoepithelial cells. In rare
      instances, the epithelial, the myoepithelial or both components of an AME may
      become malignant. Described herein is the case of a 69-year-old woman who
      presented with myoepithelial carcinoma of the breast in an AME. Malignancy of
      myoepithelial component (MEC) was evidenced by the presence of cytological
      atypia, high mitotic rate, necrosis and local invasion. Immunohistochemical study
      demonstrated strong expression of P53 and phosphorylated extracellular signal
      regulated kinase 1/2 in MEC. Laser capture microdissection technique and
      mutational analysis further revealed point mutation of the p53 gene (T-->G
      transversion at codon 270) in this population, but not in glandular epithelial
      cells or adjacent normal ductal epithelium. No mutations in exons 1 and 2 of the
      K-, H-, and N-ras genes were identified in any of the neoplastic component. To
      the authors' knowledge this is the first report of a mutation in the p53 gene in
      a malignant AME of the breast.

PMID- 16634968
TI  - Unique case of pulmonary bronchial gland type tumor with broad spectrum of cell
      differentiation from the terminal duct-acinar unit to excretory duct.
AB  - In the lung, acinic cell carcinoma (ACC) is a rare form of tumor. Reported herein
      is a unique bronchial gland-type tumor diagnosed as well-differentiated ACC that
      developed in the B9 bronchus of the left lung. Various immunohistochemical and
      histochemical staining partly satisfied the diagnosis of ACC. Moreover, this
      tumor contained various sizes of mucous cysts lined by columnar mucous cells,
      which produced abundant mucin positive for Alcian blue, which is usually present
      in mucoepidermoid carcinoma. Therefore, the present case is a unique tumor having
      a broad spectrum of cell differentiation from the terminal duct--acinar unit to
      the striated duct and excretory duct. This is the first case of unique bronchial
      gland-type tumor with mixed histological features of ACC and mucoepidermoid
      carcinoma.

PMID- 16634969
TI  - Combined hepatocellular carcinoma and cholangiocarcinoma with components of
      mucinous carcinoma arising in a cirrhotic liver.
AB  - A rare autopsy case of combined hepatocellular and cholangiocarcinoma, occurring
      in a 54-year-old man with liver cirrhosis, is presented. Initial laboratory data
      included CEA 52.1 ng/mL, DUPAN-2 1600 U/mL, AFP 2 ng/mL, and negativity for
      hepatitis B surface antigen, hepatitis B early antigen and hepatitis B core
      antibody. Ultrasonography and CT scan showed a large tumor node in the liver with
      ringed enhancement, swelling of several para-aortic lymph nodes, and ascites.
      Clinically, it was not possible to determine whether the hepatic tumor was an
      intrahepatic cholangiocarcinoma or a metastatic carcinoma. Histologically, the
      primary lesion was composed solely of hepatocellular carcinoma (HCC) with a
      trabecular pattern, and the intrahepatic metastases consisted of a variable
      admixture of HCC and cholangiocarcinoma (CC) with excessive mucin production.
      Interestingly, the tumor cell cluster showing a trabecular growth pattern
      produced mucin and had immunohistochemical expression of hepatocyte, cytokeratins
      7 and 8. It is concluded that these hepatic tumor cells had both HCC and CC
      characters.

PMID- 16634970
TI  - Incidental calcifying fibrous tumor of the stomach presenting as a polyp.
AB  - Calcifying fibrous tumor (CFT) is an uncommon lesion of uncertain cause and
      pathogenesis that has a unique histological appearance. These lesions are
      described mainly in the subcutaneous or deep soft tissues, followed by subserosal
      locations. Intrinsic visceral CFT is extremely rare. Herein is described a rare
      case of CFT that involved the gastric wall, along with a review of the
      literature. An incidental small polypoid lesion was excised during urgent surgery
      for penetrating injury at the lesser curvature in a 25-year-old man, previously
      healthy. The lesion was a well-demarcated, small (10 mm) tumor that occupied the
      submucosa. The characteristic histopathological features and the presence of
      spindle cells that express factor XIIIa allowed a diagnosis of CFT to be made.
      The present case and the review revealed that, despite their frequent
      subperitoneal location, intra-abdominal CFT might present as intrinsic visceral
      lesions and might be found incidentally. These lesions tend to be smaller when
      compared to their symptomatic counterparts. The diffuse factor XIIIa expression
      in CFT might be useful to differentiate this entity from other intra-abdominal
      soft-tissue tumors in problematic cases. Although rarity of intrinsic visceral
      CFT necessitates new cases to determine their exact biological behavior, the
      present case highlights their presence in the stomach as a symptomless small
      polypoid lesion.

PMID- 16634971
TI  - Pain- and distress-reducing interventions for venepuncture in children.
AB  - OBJECTIVE: To compare the effect of eutectic mixture of local anaesthetics (EMLA)
      and a placebo cream on reported pain and observed distress associated with
      venepuncture, and to investigate effects of procedural information before and
      distraction during venepuncture. METHODS: Children 3-12 years of age undergoing
      venepuncture under five experimental and a control condition reported their pain
      at venepuncture on visual scales. Distress was observed when the child entered
      the waiting room, just before, and during venepuncture. RESULTS: Distress
      increased over the measurement occasions, but a distress-reducing effect of EMLA
      only was found at the actual venepuncture. The placebo diminished the reported
      pain, but the effect of EMLA was larger. Procedural information and distraction
      showed no effects. CONCLUSIONS: EMLA reduces pain from venepuncture. The placebo
      effect probably results from desirable responding. Behavioural distress is a more
      direct measure than self-reported pain. More sophisticated designs should be used
      for the provision of procedural information and distraction.

PMID- 16634972
TI  - Childhood unintentional injuries: the perceived impact of the environment, lack
      of supervision and child characteristics.
AB  - BACKGROUND: Investigations into the context and causation of injury, including
      injury risks, are an essential part of the injury prevention knowledge base.
      Caregiver perceptions of childhood injury risks may assist in the design of
      safety interventions and influence the way in which an intervention is received
      within a community. METHODS: Focus groups and individual interviews were
      conducted in two low-income neighbourhoods in South Africa to collect information
      on caregiver perceptions of injury risks. The data were analysed via thematic
      content analysis. RESULTS: The results revealed that injury risks are perceived
      as multifaceted and as contributing synergistically to an injury event. Parents
      of children also tended to attribute most risks to the environment instead of
      individual action. CONCLUSIONS: Interventions including passive strategies and
      less activity from the parent may be welcomed in communities. Attention should be
      given to child injury prevention methods specifically for low-income contexts.

PMID- 16634973
TI  - Perceptions of child labour among working children in Ibadan, Nigeria.
AB  - BACKGROUND: The adverse effects of child labour on the children's psychological
      development continue to raise concerns about this public health problem
      worldwide. Several views have been presented by child health authorities, non
      governmental organizations (NGOs) and international agencies. Few studies have
      focused on the children themselves. This study sought to determine working
      children's perspective of child labour, its benefits and disadvantages and the
      working children's perceptions of themselves, and their aspirations for the
      future. METHODS: A cross-sectional study was carried out among working children
      in a large market in Ibadan, south-west Nigeria. Questionnaires were administered
      to all consenting children. RESULTS: A total of 225 children, 132 females and 93
      males, participated in the survey. Their age range was 8-17 years. A total of 103
      respondents (46%) were currently in school while 117 (52%) were out of school.
      Five respondents (2%) had never attended school. A total of 104 (46%) thought
      that children should not work. However, when asked about the benefits of working,
      81 working children (36%) felt that work provided a source of income for them, 52
      (23%) indicated that it was a way of helping their parents and 39 (17%) thought
      it was part of their training to be responsible adults. Bad company, ill health
      and road traffic accidents were the perceived ill effects of child labour. The
      majority of the children interviewed were aspiring towards artisan trades and
      very few towards professional or office jobs. A total of 106 (47%) children
      perceived themselves as less fortunate than their peers. Fifty-five children
      (24%) thought that child labour was a sign of deprivation. The perception that
      child labour is a sign of deprivation was more prevalent among child workers
      whose highest educational attainment was primary school, child workers who had
      worked for more than 6 months and those whose earnings were small. CONCLUSION: We
      recommend that school education for children should be a priority even when the
      harsh economic realities in their families force parents to send them to work
      outside the home.

PMID- 16634974
TI  - Out-of-home day care for families living in a disadvantaged area of London:
      economic evaluation alongside a RCT.
AB  - BACKGROUND: Children born into poverty have lifelong disadvantages compared with
      those more fortunate; social interventions seek to break this cycle of poverty
      and deprivation. Early Years Centres are one such intervention. These were
      established in deprived areas in the UK to provide high quality out-of-home day
      care. This paper reports the results of an economic evaluation conducted
      alongside a randomized controlled trial of one of these centres in the Borough of
      Hackney, London. METHODS: Participants were randomized to receive either high
      quality day care as provided by the centre or to other child care that they
      secured for themselves where they chose to do so. Information on resource use
      (early years education and care, as well as health and social care) was collected
      over an 18-month period; this was valued using appropriate unit costs. The cost
      of education, social and health care together with the value of productivity
      gains and out-of-pocket costs were then compared with the effectiveness of the
      intervention, increased labour force participant in mothers. RESULTS: From the
      societal perspective, the value of employment outweighs the costs of health and
      social services used, and in both groups there are cost savings. These are
      greater in the intervention group, therefore Early Years day care is an efficient
      use of resources. However, there is a net cost to the public sector of providing
      the intervention. The cost of achieving an additional mother in the labour force
      at 18 months is pound38 550 (85% CI of -pound1273, pound416 172). CONCLUSION:
      From the societal perspective, over an 18-month period, all child care is cost
      saving, but high quality day care provided by the Early Years Centre is a cost
      effective alternative to day care provided by other local services in Hackney.
      The public sector, however, incurs added expense from this intervention.

PMID- 16634975
TI  - Operationalizing the concept of resilience in child neglect: case study research.
AB  - BACKGROUND: There is a considerable amount of interest in resilience as a concept
      for child care and protection practice. This paper describes an exploratory
      project that drew on a set of case studies to explore the extent to which the
      concept of resilience can be operationalized for use with neglected children in
      the context of statutory social work. METHOD: The study was carried out within a
      local authority in Scotland and focused on the value of the concept as an aid to
      assessment and planning. The study built on a published workbook that provides a
      structure for the assessment of potential areas of resilience and gives detailed
      suggestions for intervention in six domains of a child's life. Eight neglected
      children aged between five and 11 were recruited. Six training days on the
      concept were held. Questionnaires were used to gather information about the
      theoretical frameworks already being used. At the end of the study, semi
      structured interviews were carried out with the social workers about the value of
      the concept. Assessment reports completed before and after the training were
      analysed. RESULTS: Findings indicated that participants were familiar with the
      concept of resilience and that the training helped enhance their understanding of
      the concept. Training assisted with the provision of a more structured approach
      to assessment and planning. Respondents reported that the approach enhanced their
      knowledge of the child and they were able to identify areas for development in
      the six domains. CONCLUSION: The study indicated that the concept of resilience
      can be operationalized for use with neglected children. Further, the case studies
      raised the issue of the extent to which the need for a secure base underpins
      other domains. The domain of positive values was also highlighted as an important
      area for further exploration.

PMID- 16634976
TI  - Do maternal depressive symptoms, stress and a lack of social support influence
      whether mothers living in deprived circumstances adopt safety practices for the
      prevention of childhood injury?
AB  - BACKGROUND: Maternal depressive symptoms are common, as are childhood injuries,
      particularly among the socio-economically disadvantaged. Maternal depression may
      be associated with lesser engagement in injury prevention practices. Providing
      support to mothers can reduce the risk of child injury, but the mechanism by
      which this occurs is unclear. The aim of this study was to examine the
      relationship between maternal depressive symptoms, social support and stress, and
      engagement in home safety practices to prevent injuries to pre-school children
      living in socio-economically deprived families in the UK. METHODS: Three
      questionnaires were posted to mothers of young children living in deprived areas
      in the city of Nottingham, UK, who were enrolled in the control group of a
      randomized controlled trial (RCT). The questionnaires assessed socio-demographic
      characteristics at baseline; depressive symptoms, perceived social support and
      self-reported stress 21 months later and engagement in home safety practices 24
      months post baseline. The mothers in the control group received no intervention.
      Main outcome measures were the use of fireguards, stair gates, smoke alarms,
      window locks and safe storage of medicines, sharp objects and cleaning products.
      RESULTS: One-third (36.4%) of mothers reported depressive symptoms. The most
      widely adopted safety practices were safe storage of medicines (93.5%) and use of
      smoke alarms (86.2%). The majority of mothers did not use fireguards (60.7%) or
      store sharp objects safely (63.8%). Depressive symptoms were not independently
      associated with any of the seven safety practices. Mothers reporting some lack of
      social support were more likely not to store medicines safely [odds ratio, OR,
      4.08 (95% confidence interval, CI, 1.79-9.30) compared with those reporting no
      lack of social support] and mothers reporting moderate or large amounts of stress
      were more likely not to store sharp objects safely [OR 1.77 (95% CI 1.11-2.83)
      compared with mothers reporting no or little stress] after controlling for
      confounders. CONCLUSIONS: Our results suggest that depressive symptoms, stress
      and a lack of social support are not important influences on the adoption of
      safety practices by mothers living in deprived areas in the UK, at least in the
      short term. Further work is required to explore the effects of chronic maternal
      depressive symptoms on the adoption of safety practices.

PMID- 16634977
TI  - The effect of interviewing techniques on young children's responses to questions.
AB  - BACKGROUND: Research into the effect of interviewing techniques has been
      predominantly within the paradigm of eyewitness testimony. This review focuses on
      the issues of questioning and examines whether children's responses are affected
      by questioning techniques, and whether these effects are generic to all
      interviewing contexts. METHODS: Systematic literature searches were used to
      identify areas of concern and current findings in research on interviewing young
      children (aged 4-12). RESULTS: The style and wording of questioning can affect
      children's responses and accuracy positively and negatively. These effects were
      especially apparent in interviews with the youngest children. CONCLUSIONS: The
      implications of these findings are relevant in all contexts where an adult
      questions a child. It has been demonstrated that interviewing techniques can
      affect responses from children and that it is therefore imperative that
      interviewers are aware of, understand and control their influence in order to
      elicit complete, accurate and reliable information from the child.

PMID- 16634978
TI  - Health-related issues in individuals with agenesis of the corpus callosum.
AB  - OBJECTIVES: To explore and compare the prevalence and expression of specific
      health-related variables in a large survey sample of persons with agenesis of the
      corpus callosum (ACC) and their siblings. METHODS: Caregiver surveys of
      individuals with ACC (n=189) and their siblings (n=189) provided data regarding
      diagnoses, physical features, neurological and sensory information, feeding,
      elimination and sleep concerns, and some behavioural features. RESULTS: Compared
      with their siblings, individuals with ACC had more concurrent conditions and were
      more likely to have altered pain perception and sensitivity to touch. In
      addition, individuals with ACC had more sensory deficits and abnormalities as
      well as altered patterns of feeding/eating, elimination and sleep. CONCLUSIONS:
      These data raise important questions for future research and suggest the need for
      increased vigilance by caregivers and health-care professionals of individuals
      with callosal disorders. Early detection and intervention may help prevent or
      ameliorate health problems in this population.

PMID- 16634979
TI  - The association between information and communication technology exposure and
      physical activity, musculoskeletal and visual symptoms and socio-economic status
      in 5-year-olds.
AB  - BACKGROUND: Increasing use of computers by children has raised concerns over the
      potential impact on their cognitive, social, educational, visual and physical
      development. Despite this concern, there are no large-scale studies relating the
      use of computers to specific health indicators in children as they reach school
      age. METHODS: A cross-sectional analysis of 1600 5-year-old Western Australian
      children participating in a longitudinal cohort study was conducted to ascertain
      their computer use, other activities (watching television and videos, playing
      electronic games, reading and looking at books, drawing on paper and moderate to
      vigorous physical activity), and specific health indicators. RESULTS: More than
      half (56%) of the children used computers each week. Computer use was
      significantly related to TV viewing (OR 1.97 weekday) and electronic game use
      (console games OR 2.48 weekday, 1.81 weekend; hand-held games OR 1.88 weekend)
      and negatively associated with vigorous physical activity on weekends (OR 0.72).
      Computer use was also significantly related to socio-economic indicators such as
      the mother being older (40+ years, OR 1.70 weekend, 1.73 weekday), tertiary
      educated (OR 1.63 weekend) and studying (OR 1.52 weekend, 1.41 weekday). Almost
      1% children were reported to have complained of tired or sore muscles, and 2.2%
      had complained of tired or sore eyes, after watching television or using a
      computer. CONCLUSION: A substantial proportion of 5-year-old Western Australian
      children are using computers. Computer use was related to other sedentary
      activities and less vigorous activity. While musculoskeletal and vision problems
      are not widespread, their presence and the sedentary nature of computer use is of
      public health concern.

PMID- 16634980
TI  - A qualitative investigation of changes in the belief systems of families of
      children with autism or Down syndrome.
AB  - BACKGROUND: There have been few reports of the world views, values and priorities
      of families of children with autism or Down syndrome, despite the fact that
      family belief systems are considered to be among the most important factors
      affecting the adaptation and resilience of families. METHODS: Transcripts from
      three focus groups involving 19 key informants (15 parents of children with
      autism or Down syndrome, and 4 service providers) were analysed using qualitative
      methods. RESULTS: The themes indicated that raising a child with a disability can
      be a life-changing experience that spurs families to examine their belief
      systems. Parents can come to gain a sense of coherence and control through
      changes in their world views, values and priorities that involve different ways
      of thinking about their child, their parenting role, and the role of the family.
      Although parents may grapple with lost dreams, over time positive adaptations can
      occur in the form of changed world views concerning life and disability, and an
      appreciation of the positive contributions made by children to family members and
      society as a whole. Parents' experiences indicate the importance of hope and of
      seeing possibilities that lie ahead. CONCLUSIONS: The information from this study
      may be used to provide families with an advance understanding of the changes in
      beliefs that they might undergo, and assists service providers in providing
      individualized and family-centred services and supports to families.

PMID- 16634981
TI  - Satisfaction with formal support and education for children with autism spectrum
      disorder: the voices of the parents.
AB  - INTRODUCTION: The aim of the present study was to identify and describe factors
      associated with variations in the level of parental satisfaction with formal
      support and education for children with autism spectrum disorder (ASD) in
      Flanders. METHODS: Participants were recruited by a mailing from a diagnostic
      centre for pre-schoolers and by advertisements dispersed in the Flemish parent
      organization for ASD and in services and special schools. The sample consisted of
      244 parents of children with ASD (age range: 2.69-17.81 years, male/female sex
      ratio 4:1). The data were collected using a questionnaire on experiences with
      education and support, which was compiled for the purpose of this study. The data
      resulting from the questionnaire were supplemented with information obtained from
      semi-structured in-depth interviews with a stratified sample of 15 parents.
      RESULTS AND CONCLUSIONS: The study revealed that parents experienced difficulties
      with the diagnostic process, with support and education provided by mainstream
      settings and with the accessibility of autism-specific service provisions.
      Conversely, parents reported to be satisfied with the quality of autism-specific
      support and education. Predictors of overall satisfaction were parental
      involvement in formal support, knowledge of available service provisions and time
      between first consultation and final diagnosis. Practical implications of the
      results are discussed.

PMID- 16634983
TI  - Insulin resistance--a common link between type 2 diabetes and cardiovascular
      disease.
AB  - Evidence suggests that diabetes and cardiovascular disease (CVD) may share an
      underlying cause(s), a theory known as the 'common soil' hypothesis. Insulin
      resistance is central both to the progression from normal glucose tolerance to
      type 2 diabetes and to a constellation of cardiovascular risk factors known as
      the metabolic syndrome. These risk factors include visceral obesity and
      dyslipidaemia characterized by low levels of high-density lipoprotein
      cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein
      particle levels. Changes in adipose tissue mass and metabolism may link insulin
      resistance and visceral obesity, a condition that is common in type 2 diabetes.
      Furthermore, weight reduction, increased physical activity, metformin and
      acarbose have been shown to reduce the development of type 2 diabetes in
      genetically predisposed subjects and may decrease the high cardiovascular risk of
      patients with diabetes. Some fatty acid derivatives can affect energy metabolism
      by activating peroxisome proliferator-activated receptors (PPARs), nuclear
      receptors that play a key role in energy homeostasis. These receptors represent
      an ideal therapeutic target for reducing cardiovascular risk, because they are
      involved in the regulation of both insulin action and lipid metabolism. In
      addition to lifestyle changes, PPARgamma agonists such as thiazolidinediones are
      frequently beneficial and have been shown to ameliorate insulin resistance, while
      activation of PPARalpha (e.g. by fibrates) can lead to improvements in free fatty
      acid oxidation and lipid profile, and a reduction in cardiovascular events. The
      development of agents with both PPARalpha and PPARgamma activity promises added
      benefits with amelioration of insulin resistance, delayed progression to and of
      type 2 diabetes and a reduction of CVD.

PMID- 16634984
TI  - Obesity-related cardiovascular disease: implications of obstructive sleep apnea.
AB  - Obesity and obstructive sleep apnea (OSA) often coexist. OSA has been linked to
      cardiovascular disease. Thus, OSA may contribute to the cardiovascular
      consequences of obesity. In this review, we explore clinical and
      pathophysiological interactions between obesity, cardiovascular disease and OSA.
      We discuss the mechanisms whereby OSA may contribute to hypertension,
      atherosclerosis, insulin resistance and atrial fibrillation associated with
      obesity, and emphasize the potential implications for understanding why only a
      subgroup of obese patients develop cardiovascular disease. Identification of the
      OSA-dependent and OSA-independent pathways in the cardiovascular pathophysiology
      of obesity may hold clinical and therapeutic promise.

PMID- 16634985
TI  - 'Dead in bed syndrome--a hypothesis'.

PMID- 16634986
TI  - Adiponectin--a key adipokine in the metabolic syndrome.
AB  - Adiponectin is a recently described adipokine that has been recognized as a key
      regulator of insulin sensitivity and tissue inflammation. It is produced by
      adipose tissue (white and brown) and circulates in the blood at very high
      concentrations. It has direct actions in liver, skeletal muscle and the
      vasculature, with prominent roles to improve hepatic insulin sensitivity,
      increase fuel oxidation [via up-regulation of adenosine monophosphate-activated
      protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin
      exists in the circulation as varying molecular weight forms, produced by
      multimerization. Recent data indicate that the high-molecular weight (HMW)
      complexes have the predominant action in the liver. In contrast to other
      adipokines, adiponectin secretion and circulating levels are inversely
      proportional to body fat content. Levels are further reduced in subjects with
      diabetes and coronary artery disease. Adiponectin antagonizes many effects of
      tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin
      production. Furthermore, adiponectin secretion from adipocytes is enhanced by
      thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus,
      adiponectin may be the common mechanism by which TNF-alpha promotes, and the
      thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin
      receptors, termed AdipoR1 and AdipoR2, have been identified and these are
      ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and
      has a prominent action to activate AMPK, and hence promote lipid oxidation.
      AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity
      and reduces steatosis via activation of AMPK and increased peroxisome
      proliferator-activated receptor alpha ligand activity. T-cadherin, which is
      expressed in endothelium and smooth muscle, has been identified as an adiponectin
      binding protein with preference for HMW adiponectin multimers. Given the low
      levels of adiponectin in subjects with the metabolic syndrome, and the beneficial
      effect of the adipokine in animal studies, there is exciting potential for
      adiponectin replacement therapy in insulin resistance and related disorders.

PMID- 16634987
TI  - Insulin increases gelatinase activity in rat glomerular mesangial cells via ERK-
      and PI-3 kinase-dependent signalling.
AB  - Diabetic nephropathy is associated with increased accumulation of the
      extracellular matrix (ECM) in the kidney, which ultimately leads to kidney
      failure. This may occur due to excessive synthesis of ECM components or reduced
      degradation, a process primarily mediated by matrix metalloproteinases (MMPs).
      The direct effect of insulin on ECM synthesis and degradation in glomerular
      mesangial cells (GMCs) is unclear. Here, we show an increased gelatinase activity
      in conditioned media from insulin-treated rat GMCs, determined by gelatin
      zymography. Furthermore, we show using the specific inhibitors LY294002 and
      PD98059 that insulin induced increased gelatinase activity via an intracellular
      signalling mechanism involving phosphatidylinositol-3 kinase (PI-3K) and the
      extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein
      kinases (MAPKs) respectively. In addition, we demonstrate that PI-3 kinase and
      ERK1/2 MAPK are activated by insulin in GMCs. The appearance of protease activity
      at approximately 72 kDa suggested that MMP-2 activity may be induced by insulin,
      however, we did not detect an increase in MMP-2 expression by Western blotting.
      In summary, our results suggest that insulin can induce gelatinase activity in
      GMCs, and it is possible that loss of this input in insulin-resistant type 2
      diabetic individuals may contribute to ECM accumulation and the development of
      nephropathy.

PMID- 16634988
TI  - Effect of sibutramine and of cognitive-behavioural weight loss therapy in obesity
      and subclinical binge eating disorder.
AB  - AIM: In this randomized, double-blind, placebo-controlled study, the effect of
      sibutramine and cognitive-behavioural weight loss (cognitive-BWL) treatment was
      assessed in obese subjects with and without subclinical binge eating disorder
      (sBED). METHODS: Seventy-three obese participants were recruited from the
      community, 29 with and 44 without sBED. Subjects were randomly assigned to a 16
      week treatment with either sibutramine or placebo while simultaneously
      participating in a cognitive-behavioural weight loss treatment. RESULTS: Intent
      to-treat analysis showed moderate weight loss after treatment in all subject
      groups. Treatment with BWL programs and sibutramine leads to a higher weight loss
      in all subjects compared with that in patients who had undergone BWL programs
      alone. Subjects with sBED significantly reduced their binge episodes during
      treatment, but with no augmenting effect of sibutramine. DISCUSSION: Our results
      yield further evidence that sBED is associated with characteristics comparable
      with full-syndrome BED, significantly differing from those of obesity alone.
      These findings call for a systematic assessment of eating behaviour before
      starting obesity treatment.

PMID- 16634989
TI  - Effect of fat distribution on endothelial-dependent and endothelial-independent
      vasodilatation in healthy humans.
AB  - AIM: The present study aims to explore the relationship between inflammatory
      cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers
      of fat distribution and endothelial function in healthy people across a wide
      range of body fatness. METHODS: Seventy-three healthy people (44 women; age
      range: 24-64 years) with body mass index (BMI) range of 18.6-73.1 kg/m2 were
      recruited. All participants underwent assessment of conduit artery endothelial
      dependent vasodilatation by using flow-mediated vasodilatation (FMD) of the
      brachial artery and endothelial-independent vasodilatation to sublingual GTN.
      They had blood taken for measurement of plasma markers of glucose homeostasis
      (fasting insulin and glucose), systemic inflammation (interleukin-6 (IL-6), C
      reactive protein (CRP) and tumour necrosis factor-alpha receptor 2 (TNF-alpha
      R2)) and lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL)
      and triglycerides). Morphometric assessment (waist circumference, BMI and waist
      to-hip ratio (WHR)) and systolic and diastolic arterial pressure were also
      measured. RESULTS: Markers of total body fat/fat distribution (waist
      circumference, BMI and WHR), inflammation (IL-6, CRP and TNF-alpha R2),
      metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and
      diastolic) correlated with FMD. Among these measurements, WHR was the only
      independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an
      important marker of endothelial dysfunction in healthy people across a wide range
      of body fatness.

PMID- 16634990
TI  - Phenotypic variations between a fat-preferring strain and a macronutrient non
      preferring strain of mouse.
AB  - AIM: This study aims to establish a model that will allow the comparison of the
      phenotypic variations between a fat-preferring strain and a macronutrient non
      preferring strain of mouse. METHODS: Five strains (AKR, A/J, ARC, C57Bl/6 and
      BALB/c) were fed a two-choice diet (high-fat/low-carbohydrate and low-fat/high
      carbohydrate) for 30 days. Following completion of the 30-day feeding period, the
      brains of the fat-preferring and macronutrient non-preferring mice were removed
      for the analysis of the expression of the genes - agouti-related peptide (AgRP)
      and pro-opiomelanocortin (POMC). RESULTS: Upon completion of the experiment, it
      was found that the C57Bl/6 strain was the strongest fat preferrer consuming 72%
      of their calories from the high-fat diet, whereas the BALB/c was found to have no
      macronutrient preference. Using in situ hybridization techniques, no significant
      differences in the expression of POMC were found between the two strains. It was,
      however, showed that the BALB/c mice had a 33.7% higher expression level of AgRP
      than the C57Bl/6 mice. CONCLUSIONS: The lower expression level of AgRP in the
      C57Bl/6 mice may be suggestive of a defensive response to their chronic
      preferential consumption of the high-fat diet. However, the wide variety of
      neuroregulatory signals involved in macronutrient preference along with the
      possibility of the occurrence of post-transcriptional effects suggests further
      biological analyses need to be performed using this model.

PMID- 16634991
TI  - Effects of running exercise on fibre-type distribution of soleus and plantaris
      muscles in diabetic Otsuka Long-Evans Tokushima fatty rats.
AB  - AIM: Effect of running exercise on fibre-type distributions of the slow soleus
      and fast plantaris muscles was investigated in male Otsuka Long-Evans Tokushima
      fatty rats (OLETF) as an animal model of spontaneous type 2 diabetes mellitus.
      METHODS: Five-week-old OLETF rats were allowed to exercise voluntarily in running
      wheels for 32 days and the data were compared with those of age-matched non
      exercised OLETF and non-diabetic Long-Evans Tokushima Otsuka rats (LETO).
      RESULTS: In the soleus muscle, a higher percentage of type I fibres was observed
      in non-exercised OLETF rats compared with LETO rats, and there were no type IIA
      fibres in non-exercised OLETF rats. In the plantaris muscle, a higher percentage
      of type IIB fibres and a lower percentage of type I and type IIA fibres were
      observed in non-exercised OLETF rats compared with LETO rats. In contrast, there
      were no differences in the fibre-type distribution of soleus and plantaris
      muscles between exercised OLETF and LETO rats. The body weight and type I fibre
      percentage of the soleus muscle were related to the running distance in exercised
      OLETF rats. White adipose tissue weight, HbA(1c) and blood insulin and glucose
      concentrations were lower in exercised OLETF rats than in non-exercised OLETF
      rats, irrespective of the running distance. There was a difference in the gene
      expression pattern of the soleus muscle among LETO rats, non-exercised OLETF and
      exercised OLETF rats. CONCLUSION: Running exercise can inhibit diabetes
      associated type shifting of fibres, which is more apparent with postnatal growth,
      in skeletal muscles of diabetic OLETF rats, as a result of mRNA expression change
      in muscle.

PMID- 16634992
TI  - Energy expenditure, body composition and insulin response to glucose in male
      twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor
      gene.
AB  - AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of
      the beta3-adrenergic receptor (beta3AR) gene has been associated with an
      increased prevalence of obesity, insulin resistance and type 2 diabetes. In this,
      decreased rates of energy expenditure and impaired insulin secretion could play a
      role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we
      examined insulin response to glucose by an oral glucose tolerance test (OGTT), a
      frequently sampled intravenous glucose tolerance test (FSIGT), body composition
      by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy
      expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for
      the Trp64Arg polymorphism showed significantly lower fat mass independent of the
      method used, and significantly lower fasting insulin and glucose concentrations
      compared with their homozygous wild-type co-twins. Correspondingly, insulin
      resistance and insulin secretion determined by homeostasis model assessment were
      significantly lower in twins carrying the Trp64Arg polymorphism. However, there
      were no significant differences in adiponectin levels, insulinogenic index
      assessed by OGTT, or insulin sensitivity, acute insulin response to glucose,
      glucose effectiveness or insulin disposition index assessed by minimal modelling
      of the FSIGT. Furthermore, there were no differences in sleeping, resting or post
      prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in
      genetic and environmental background, the Trp64Arg polymorphism of the beta3AR
      gene is associated with lower fat mass, fasting insulin levels and an appropriate
      insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is
      unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.

PMID- 16634993
TI  - Effect of a nutritional liquid supplement designed for the patient with diabetes
      mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and
      insulin sensitivity in healthy subjects.
AB  - AIM: To identify the effect of a nutritional liquid supplement designed for the
      patient with diabetes mellitus (Glucerna SR) in single administration on the
      postprandial glucose state, insulin secretion and insulin sensitivity in healthy
      subjects. METHODS: A randomized, single-blind, cross-over, clinical trial was
      carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic
      profile, which included glucose level, insulin, total cholesterol, high-density
      lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine,
      and uric acid, was measured. Subjects received a single administration of 300
      kcal, gauged with water at 350 ml, of each of the following (at least 3 days
      apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or
      Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and
      120 min later, glucose and insulin concentrations were measured. Areas under the
      curve of glucose and insulin were calculated. First-phase and total insulin
      secretions and insulin sensitivity were also estimated. RESULTS: Glucose level at
      120 min was significantly lower after receiving Ensure high calcium or Glucerna
      SR. Administration of Glucerna SR resulted in a significant reduction in the
      areas under the curve of glucose and insulin, as well as in total insulin
      secretion with a tendency to be lower in their first phase. Insulin sensitivity
      was increased. CONCLUSIONS: A single administration of Glucerna SR to healthy
      subjects decreased the postprandial glucose and insulin states, as well as the
      insulin secretion; insulin sensitivity increased.

PMID- 16634994
TI  - Degradation in insulin sensitivity with increasing severity of the metabolic
      syndrome in obese postmenopausal women.
AB  - AIM: We investigated the relationship between insulin sensitivity and the graded
      increase in the number of features of the metabolic syndrome in a cross-sectional
      sample of obese postmenopausal women. We hypothesized that insulin sensitivity
      would deteriorate with an increased number of metabolic syndrome phenotypes.
      METHODS: Insulin sensitivity was measured in 75 obese postmenopausal women (age:
      57.3 +/- 5.3 years; BMI: 32.8 +/- 4.5 kg/m2) by using both the hyperinsulinaemic
      euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the
      metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29
      mmol/l), fasting triglycerides (> or =1.7 mmol/l), blood pressure (> or =130/> or
      =85 mmHg) and fasting glucose (> or =6.1 mmol/l). Participants were classified
      into three categories based on the presence of metabolic syndrome phenotypes: 0-1
      vs. 2 vs. > or =3 features of the metabolic syndrome. RESULTS: We found that
      insulin sensitivity decreased in a graded fashion (12.19 +/- 3.2 vs. 11.80 +/-
      2.3 vs. 9.29 +/- 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95
      +/- 1.1 vs. 3.28 +/- 1.3 vs. 4.65 +/- 2.2), as the number of features of the
      metabolic syndrome increased from 0-1 to > or =3. When insulin sensitivity was
      statistically adjusted for visceral fat (as measured by computed tomography) and
      plasma triglycerides, the differences among groups were abolished. CONCLUSIONS:
      These findings suggest that a decreased insulin sensitivity is associated with
      increased features of the metabolic syndrome in obese postmenopausal women and
      that visceral fat as well as plasma triglyceride accumulation might be potential
      mediators of this relationship.

PMID- 16634995
TI  - The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients
      with moderate renal insufficiency.
AB  - BACKGROUND: The renoprotective effect of angiotensin II antagonists has been
      demonstrated in type 2 diabetic patients with nephropathy but similar data on
      angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the
      efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and
      renal clearance, in 38 type 2 diabetic patients with moderate renal impairment
      (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a
      single-centre, randomized, double-blinded, placebo-controlled trial comparing
      fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive
      treatment over a 2-year period. The primary endpoints were the rate of change and
      the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine
      clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range
      47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For
      similar blood pressure control, the percentage change of UAE in patients with
      microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/-
      28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In
      the fosinopril group, the rate of change of endogenous CrCl was slower than the
      placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The
      incidence of adverse events was similar between the two groups. CONCLUSIONS:
      Fosinopril treatment reduced albuminuria and rate of decline in renal function in
      type 2 diabetic patients with moderate renal insufficiency and did not increase
      the incidence of adverse events.

PMID- 16634996
TI  - Insulin stimulates arterial neointima formation in normal rats after balloon
      injury.
AB  - AIM: Insulin resistance in patients is associated with increased atherosclerosis
      and arterial restenosis. It is thought that the concomitant hyperinsulinaemia
      exacerbates vascular disease because resistance to insulin-induced glucose
      disposal is associated with resistance to certain effects of insulin which
      inhibit, but with no resistance to other effects which promote, neointimal
      hyperplasia. We sought to determine the net effect of hyperinsulinaemia on
      neointimal hyperplasia in normal animals. METHODS: Rats were infused with or
      without insulin for 16 days and the carotid artery injured by balloon catheter on
      day 2. RESULTS: Steady-state serum insulin concentrations were 0.56 +/- 0.04 and
      1.25 +/- 0.05 nm for control and hyperinsulinaemic rats respectively (p < 0.01).
      Systolic blood pressures, weights and serum glucose levels were not affected by
      hyperinsulinaemia. Fourteen days after injury, the neointima-to-media area ratio
      was 0.72 +/- 0.07 and 1.39 +/- 0.15 for control and hyperinsulinaemic rats
      respectively (p < 0.05). Media area was unaffected by hyperinsulinaemia.
      CONCLUSIONS: The effects of hyperinsulinaemia which promote neointimal
      hyperplasia after balloon injury of rat carotid artery predominate over the
      effects which inhibit it even in normal animals.

PMID- 16634998
TI  - Food for thought on canine developmental orthopedic disease.

PMID- 16634999
TI  - Associations between canine juvenile weight gain and coxofemoral joint laxity at
      16 weeks of age.
AB  - OBJECTIVE: Evaluation of the relationship between canine weight gain from 6 to 15
      weeks of age and passive coxofemoral joint (CFJ) laxity at 16 weeks of age. STUDY
      DESIGN: Longitudinal cohort study. ANIMALS: Full- or half-sibling hounds (n =
      56). METHODS: Hounds were weighed weekly from 6 to 15 weeks of age. Individual
      average daily gain (ADG) was calculated for each week (weekly) and for the study
      (overall). PennHIP distraction index (DI) was determined for each CFJ at 16
      weeks. Mixed effects linear models were evaluated for associations of DI (highest
      and mean) with 15-week weight and ADGs (actual or normalized). Left and right DIs
      were compared with a Student's paired t-test. Significance was set at P<.05.
      Trends were considered at P<.10. RESULTS: Mean (+/-SD) 16-week DI score and 15
      week weight was 0.67 +/- 0.16 and 12.5 +/- 1.8 kg, respectively. Within animal
      left and right DIs were not significantly different. There were no significant
      associations between DI and any of the weight gains evaluated. There was a trend
      for a negative relationship between normalized 14-week ADG and DI in one
      statistical model. CONCLUSIONS: Weight gain from 6 to 15 weeks of age was
      unrelated to 16-week PennHIP DI in a homogenous canine population with moderate
      to-severe CFJ joint laxity. CLINICAL RELEVANCE: Based on our results, ad libitum
      feeding between 6 and 15 weeks of age does not appear to have an adverse impact
      on joint laxity at 16 weeks of age as measured by the PennHIP DI.

PMID- 16635000
TI  - Comparison of arthroscopic approaches and accessible anatomic structures during
      arthroscopy of the caudal pouches of equine femorotibial joints.
AB  - OBJECTIVE: To (1) describe a caudal approach to equine medial and lateral
      femorotibial (FT) joints and (2) illustrate the complex anatomic detail of the
      caudal compartments of the lateral FT joint. STUDY DESIGN: Prospective
      experimental study. ANIMALS: Cadaveric equine hindlimbs (n = 36; 26 horses) and 6
      horses (11 hind limbs). METHODS: Stifles (n = 8) were dissected and 10 FT joints
      were injected with silicone. Arthroscopic exploration (n = 29) was performed,
      followed by dissection to determine sites and structures penetrated during entry.
      RESULTS: A more caudal approach to the caudal pouch of the medial FT improved
      anatomic observation. A more caudal approach to the caudal pouch of the lateral
      FT joint occasionally caused damage to the common peroneal nerve; however, after
      reverting to the previously described approach, damage was avoided. CONCLUSION:
      Arthroscopy of the caudal pouch of the medial FT joint was facilitated using a
      more caudomedial approach, which improved observation of intrasynovial
      structures, most importantly, the caudal cruciate ligament and caudal horn of the
      medial meniscus. A more caudal approach to the caudal pouch of the lateral FT
      joint cannot be safely performed without risk to the common peroneal nerve and
      therefore the standard caudal approach is described in detail. CLINICAL
      RELEVANCE: A caudomedial arthroscopic approach allows improved surgical
      assessment of meniscal or caudal cruciate ligament injury. Care should be
      exercised when exploring the caudal pouch of the lateral FT joint because the
      common peroneal nerve is variably located and could easily be damaged during
      arthroscope or instrument insertion, especially if the limb is minimally flexed.

PMID- 16635001
TI  - Arthroscopic approaches to the palmar aspect of the equine carpus.
AB  - OBJECTIVE: To identify sites for arthroscopic access to the palmar aspects of the
      antebrachiocarpal (AC) and middle carpal (MC) joints, and describe visible carpal
      bone surfaces for each approach. STUDY DESIGN: Prospective experimental study.
      ANIMALS: Equine carpi: 16 cadavers, 8 live horses. METHODS: A latex model was
      used to identify possible sites for arthroscopic access to the palmar aspects of
      the AC and MC joints. Carpi (n = 24) were examined arthroscopically and
      arthroscopic access sites and visible carpal bone surfaces were described.
      RESULTS: Arthroscopic approaches and instrument portals were developed for the
      medial and lateral aspects of the palmar pouches of the AC and MC joints. The
      palmar surface of the radial carpal bone and radius, and the dorsal articular
      surfaces of the accessory carpal bone, could be viewed using palmar approaches to
      the AC joint. The palmar aspect of the radial, third and second carpal bones
      (medially) and ulnar and fourth carpal bones (laterally) could be observed using
      a palmar approach to the MC joint. CONCLUSIONS: Arthroscopic access, using
      separate medial and lateral portals to the AC and MC joints, allowed assessment
      of portions of the caudodistal radius, the palmar surfaces of the radial, ulnar,
      second, third and fourth carpal bones, and the dorsal aspect of the accessory
      carpal bone. CLINICAL RELEVANCE: Arthroscopic approaches to the palmar aspect of
      the carpus could be used to remove fracture fragments, and to assess the medial
      palmar intercarpal ligaments.

PMID- 16635002
TI  - Mesenchymal stem cells and bone regeneration.
AB  - OBJECTIVE: To review the role of mesenchymal stem cells (MSC) in bone formation
      and regeneration, and outline the development of strategies that use MSC in bone
      healing and regeneration. STUDY DESIGN: Literature review. METHODS: Medline
      review, synopses of authors' published research. RESULTS: The MSC is the basic
      cellular unit of embryologic bone formation. Secondary bone healing mimics bone
      formation with proliferation of MSC then their differentiation into components of
      fracture callus. Bone regeneration, where large amounts of bone must form, mimics
      bone healing and can be achieved with MSC combined with strategies of
      osteogenesis, osteoinduction, osteoconduction, and osteopromotion. MSC based
      strategies first employed isolated and culture expanded stem cells in an
      osteoconductive carrier to successfully regenerate a critical segmental defect in
      the femur of dogs, which was as effective as autogenous cancellous bone. Because
      MSC appeared to be immunologically privileged, a study using mismatched
      allogeneic stem cells demonstrated that these cells would regenerate bone without
      inciting an immunologic response, documenting the possibility of banked
      allogeneic MSC for bone regeneration. A technique was developed for selectively
      retaining MSC from large bone marrow aspirates at surgery for bone regeneration.
      These techniques utilized osteoconductive and osteoinductive carriers and
      resulted in bone regeneration that was similar to autogenous cancellous bone.
      CONCLUSION: MSC can be manipulated and combined with carriers that will result in
      bone regeneration of critically sized bone defects. CLINICAL RELEVANCE: These
      techniques can be employed clinically to regenerate bone and serve as an
      alternative to autogenous cancellous bone.

PMID- 16635003
TI  - Comparison of biopsy samples obtained using standard endoscopic instruments and
      the harmonic scalpel during laparoscopic and laparoscopic-assisted surgery in
      normal dogs.
AB  - OBJECTIVES: To compare tissue specimens of canine abdominal organs collected by
      standard techniques (ST) and harmonic scalpel (HS) and to determine the effect of
      each technique on wound healing. STUDY DESIGN: Experimental. ANIMALS: Twelve
      dogs. METHODS: Paired biopsy samples (ST, HS) were collected from liver, spleen,
      adrenal gland, pancreas, stomach, jejunum, and bladder using laparoscopic or
      laparoscopic-assisted methods. Hemorrhage at biopsy sites was assessed (present
      or absent). Specimens were evaluated for diagnostic quality and histologic
      changes. Dogs were necropsied at 4 or 14 days postoperatively. RESULTS: HS
      incision caused less frequent hemorrhage of all organs except spleen. HS
      specimens had more coagulation necrosis than ST specimens, but both techniques
      yielded specimens that were sized similarly and were of diagnostic quality. At
      necropsy, HS biopsy sites of the stomach, jejunum, bladder, adrenal gland, and
      pancreas were more hyperemic than ST sites. There were more adhesions at jejunal
      and pancreatic ST biopsy sites. HS biopsy sites had more coagulation necrosis at
      days 4 and 14 postoperatively. Differences in fibrin deposition, inflammation,
      and fibrosis were present at biopsy sites of some organs at days 4 or 14 and in
      comparisons between days 4 and 14. CONCLUSIONS: Diagnostic quality biopsy
      specimens were obtained with HS and ST. Although HS-induced gross and histologic
      changes during the first 2 postoperative weeks, no clinical complications were
      observed. CLINICAL RELEVANCE: Both HS and ST can yield specimens with minimal
      hemorrhage and HS resulted in no apparent postoperative problems in normal dogs.
      Although HS caused more inflammation and adhesions at biopsy sites of the
      pancreas, adrenal gland, and jejunum, no clinical complications occurred.

PMID- 16635004
TI  - Hemodynamic effects of interpleural lidocaine and bupivacaine combination in
      anesthetized dogs with and without an open pericardium.
AB  - OBJECTIVE: To identify dysrhythmias and hemodynamic changes after lidocaine and
      bupivacaine infusion into the interpleural space with an open pericardium. STUDY
      DESIGN: Experimental study. ANIMALS: Six adult dogs. METHODS: Systemic arterial
      pressure and electrocardiogram were recorded. A 7.5 Fr Swan-Ganz catheter was
      advanced to the level of the main pulmonary artery to record pulmonary arterial
      pressure. Cardiac output was measured by a thermodilution technique. A
      pericardial window (PW) was performed in 3 dogs using thoracoscopy. Hemodynamic
      variables were recorded before and 15 minutes after injection of lidocaine (1.5
      mg/kg) and bupivacaine (1.5 mg/kg) into the pleural space in the control group
      and in the pericardial space for the PW group. A randomized-block ANOVA for
      repeated measures was used to evaluate the effect of local anesthetic
      administration on hemodynamic and electrophysiologic variables in dogs with a
      pericardectomy. RESULTS: Each dog maintained sinus rhythm. Infusion of local
      anesthetic induced a significant increase in right ventricular diastolic pressure
      (P = .002) and a significant decrease in stroke volume (P = .047) in both groups;
      however, the effects were not significantly different between groups.
      CONCLUSIONS: Infusion of lidocaine and bupivacaine, either intrapleural or in the
      pericardial space, had a mild detrimental effect on cardiac output. CLINICAL
      RELEVANCE: Intrapleural administration of lidocaine and bupivacaine at a
      therapeutic dose can be used safely in healthy dogs with a pericardectomy.

PMID- 16635005
TI  - In situ and ex vivo evaluation of an arthroscopic indentation instrument to
      estimate the health status of articular cartilage in the equine
      metacarpophalangeal joint.
AB  - OBJECTIVE: To evaluate an arthroscopic indentation instrument (Artscan 200) for
      assessment of the health status of equine articular cartilage. STUDY DESIGN: In
      vitro experiment using equine isolated proximal phalanx (P1) specimens. SAMPLE
      POPULATION: P1 specimens from 39 horses (aged 1.5-22 years). METHODS:
      Reproducibility was tested by determination of the coefficient of variation (CV).
      Dynamic modulus and cartilage degeneration index (CDI) values were measured at 2
      predefined sites (site 1, joint margin; site 2, joint center) to assess the
      accuracy and to evaluate the relation with surface integrity. RESULTS: CV was
      9.0%. A significant decrease in indenter force was identified when dynamic
      modulus values decreased to <2.5 MPa (range of tested samples 0.9-8.1 MPa) and
      when CDI values at site 1 increased to >50% (range 5.4-72.8%). CONCLUSIONS:
      Technique reproducibility was adequate but accuracy was limited. The device
      identified degeneration-associated decreases in cartilage stiffness only when the
      mechanical properties of the cartilage were considerably changed. CLINICAL
      RELEVANCE: Usefulness of this indentation instrument during arthroscopic surgery
      would be limited in the initial phase of OA-like cartilage degeneration, but may
      yield important information in more advanced OA.

PMID- 16635006
TI  - Surgery of metastatic anal sac adenocarcinoma in five dogs.
AB  - OBJECTIVE: To identify survival and morbidity information after surgery for
      metastases from apocrine gland anal sac adenocarcinomas (AGACA). STUDY DESIGN:
      Retrospective study. ANIMALS: Five dogs with AGACA. METHODS: Medical records of
      dogs that had surgery for treatment of metastatic AGACA between 1993 and 2003
      were reviewed. Criteria for inclusion required that dogs had lymphadenectomy,
      with or without further debulking, as part of their treatment for metastatic
      AGACA and that the tissue was histologically confirmed as consistent with the
      primary AGACA. Signalment, history, physical examination findings,
      clinicopathologic data, imaging findings, surgical complications, number of
      surgeries, survival times, and cause of death were recorded. All dogs had a
      complete blood count, serum biochemical profile, serum electrolytes, 3-projection
      thoracic radiographs, abdominal radiographs and/or abdominal ultrasonography, and
      histologic confirmation of metastatic AGACA invading the regional lymph nodes and
      caudal abdomen. RESULTS: No surgical complications occurred. Three dogs were
      euthanatized; median survival, 20.6 months. One dog was alive for 19 months
      postoperatively. One dog had 5 sequential surgical procedures: 1 iliac
      lymphadenectomy and 4 debulking procedures of metastatic neoplastic tissue around
      and dorsal to the iliac vessels extending into the pelvic cavity, and was alive
      54 months after initial surgery. CONCLUSION: Dogs with anal sac adenocarcinoma
      metastases to the iliac lymph nodes can experience long-term survival after
      surgical excision of the metastatic lesion. CLINICAL RELEVANCE: Lymphadenectomy
      may afford long-term survival to patients with metastatic anal sac
      adenocarcinoma.

PMID- 16635007
TI  - Median sternotomy closure in dogs: a mechanical comparison of technique
      stability.
AB  - OBJECTIVE: To evaluate the mechanical properties of canine median sternotomy
      closure using double-loop cerclage compared with other commonly used cerclage
      sternotomy closure patterns. STUDY DESIGN: Experimental study. SAMPLE POPULATION:
      Forty canine cadaveric sternal segments. METHODS: Median sternotomy-wire
      constructs were loaded to failure in a materials testing machine. Each construct
      was radiographed before and after testing. Specific wire configurations tested
      were: 2 single twist cerclage centered on the sternebrae, single twist figure of
      8 pattern centered on the sternal synchondrosis, double twist figure of 8 pattern
      centered on the sternal synchondrosis, 2 double-loop cerclage centered on the
      sternebrae, and 1 double-loop cerclage centered on the sternal synchondrosis.
      Wire configurations were compared by craniocaudal translation of sternabrae on
      pre-test radiographs, and displacement during loading, and mode of failure, based
      on analysis of test video, and post-test radiographs. RESULTS: Double-loop
      cerclage did not provide superior mechanical stabilization of median sternotomy.
      Both figure of 8 patterns had the least displacement at higher loads. Two single
      twists that were centered on sternebrae were least able to prevent displacement
      at higher loads, caused the most craniocaudal translation before testing, and
      fractured more often at loads < or = 200 N compared with other configurations.
      CONCLUSION: Sternal wiring techniques stabilizing sternal synchondroses had the
      least displacement. Overall, figure of 8 cerclage appeared most suitable because
      they minimized displacement at high loads and facilitated accurate reduction
      during tensioning. CLINICAL RELEVANCE: In closing canine sternotomy, figure of 8
      cerclage may be most suitable. Double-loop cerclage centered on the sternal
      synchondrosis should be avoided because of wire failure at high loads.

PMID- 16635008
TI  - Pullout strength for three suture patterns used for canine tracheal anastomosis.
AB  - OBJECTIVE: To compare pullout strength of 3 suture patterns used for canine
      tracheal anastomosis. STUDY DESIGN: Experimental study. SAMPLE POPULATION:
      Cadaveric canine tracheae (n = 20). METHOD: Tracheal segments were anastomosed
      with 1 of 3 suture patterns: simple continuous, simple interrupted, and simple
      interrupted reinforced with horizontal mattress, each encircling annular
      cartilage rings adjacent to the transection site. Horizontal mattress sutures
      encircled the annular rings proximal and distal to the rings closest to the
      anastomosis. Each construct was distracted (0.5 mm/s) in a materials testing
      machine to failure. Load-displacement curves were generated and failure load
      (pullout strength) determined and mode of failure recorded. RESULTS: Tracheal
      anastomosis with a simple interrupted pattern was significantly weaker (mean+/-SD
      pullout strength, 102.55+/-30.14 N) than simple continuous (135.53+/-15.47 N) or
      simple interrupted plus horizontal mattress (132.39+/-21.46 N), which were not
      different from each other. Mode of failure was consistently by suture tear out.
      CONCLUSIONS: Both simple continuous and simple interrupted reinforced with
      horizontal mattress suture patterns have significant biomechanical advantage over
      a simple interrupted pattern alone in canine cadaveric tracheal anastomosis. The
      simple continuous pattern had the least variability in pullout strength. CLINICAL
      RELEVANCE: A simple continuous technique should be considered when selecting a
      tension-relieving pattern for canine tracheal anastomosis. It offers the same
      biomechanical advantage as a simple interrupted pattern reinforced with a
      horizontal mattress pattern and its strength appears to be reliably maintained
      when tested in canine cadaver tracheae.

PMID- 16635009
TI  - Use of the lip-to-lid flap for replacement of the lower eyelid in five cats.
AB  - OBJECTIVE: To report outcomes after reconstruction of the lower eyelid following
      resection of squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective study.
      ANIMALS: Five cats (6 eyelids). METHODS: Case records were reviewed for breed,
      sex, surgical findings, complications, and outcome. RESULTS: Six eyelids were
      reconstructed in 5 cats; functional outcome was excellent. Neither wound
      breakdown nor flap failure occurred. An area of superficial necrosis occurred in
      1 cat; this spared the eyelid margin and healed by secondary intention without
      any cosmetic or functional effect. One cat was euthanatized 18 months later
      because of a nasal mass. The relationship between the nasal mass and the
      previously excised SCC was not established. CONCLUSIONS: Reconstruction of the
      lower eyelid using a lip-to-lid flap yields satisfactory functional and cosmetic
      results in cats. CLINICAL RELEVANCE: A lip to lid flap is a successful form of
      single-stage reconstruction after lower eyelid excision in cats.

PMID- 16635010
TI  - Results of thyroidectomy in 101 cats with hyperthyroidism.
AB  - OBJECTIVE: To describe outcome after thyroidectomy in hyperthyroid cats, with
      emphasis on peri- and postsurgical complications and recurrence. STUDY DESIGN:
      Retrospective study. ANIMALS: One hundred and one hyperthyroid cats. METHODS:
      Diagnostic work-up included preoperative measurement of plasma calcium, sodium,
      potassium, urea, and creatinine concentrations, and thyroid scintigraphy. A
      modified intracapsular dissection technique was performed. Postoperatively,
      parathyroid gland function was evaluated by measuring plasma calcium
      concentration several times daily. Outcome was obtained by standard telephone
      questionnaire. RESULTS: Thyroid scintigraphy revealed ectopic hyperplastic
      thyroid tissue (EHTT) in 9 cats. Preoperatively, 29 of 91 cats had hypokalemia.
      Two cats died within 3 days after surgery and 5 of 86 cats developed
      postoperative transient hypocalcemia. On histologic examination, thyroid
      carcinoma was identified in 3 of 88 cats. Hyperthyroidism recurred in 5 cats
      between 3 and 59 months; 4 of these cats had EHTT preoperatively. The difference
      in recurrence rate between hyperthyroid cats with and without EHTT was
      significant (P<.001). CONCLUSION: Complications were uncommon after thyroidectomy
      performed by an experienced surgeon when combined with an anesthetic regimen
      associated with minimal adverse cardiovascular effects. Hyperthyroid cats with
      EHTT had a significantly higher chance of recurrence. CLINICAL RELEVANCE:
      Thyroidectomy is associated with a low incidence of surgical complications and is
      an effective treatment for hyperthyroid cats when radioactive iodine therapy is
      not available. Preoperative thyroid scintigraphy is advised. Surgery is not
      recommended when EHTT is present, because of a higher chance of developing
      recurrent disease.

PMID- 16635011
TI  - The effect of tibial plateau angle on ground reaction forces 4-17 months after
      tibial plateau leveling osteotomy in Labrador Retrievers.
AB  - OBJECTIVE: To assess the relationship between postoperative tibial plateau angle
      (TPA) and ground reaction forces (GRFs) in Labrador Retrievers at least 4-months
      after tibial plateau leveling osteotomy (TPLO) surgery. STUDY DESIGN: A
      retrospective longitudinal study. ANIMALS: Thirty-two Labrador Retrievers with
      unilateral cranial cruciate ligament disease that had TPLO and concurrent
      meniscal surgery. METHODS: TPA and GRFs were measured pre- and > or = 4 months
      postoperatively. Preoperative GRFs, preoperative TPA, duration of injury,
      postoperative TPA and degree of rotation were each compared with postoperative
      GRFs using correlation analysis. Dogs were also grouped by postoperative TPA and
      compared using 1-way analysis of variance (ANOVA). Postoperative function was
      compared with meniscal release/meniscectomy, patient age, sex, body weight and
      follow-up time using ANOVA. RESULTS: No significant relationship was found
      between preoperative GRFs, preoperative TPA, duration of injury, postoperative
      TPA, degree of rotation, or meniscal release/meniscectomy and postoperative
      function. Mean preoperative GRFs for all dogs were 28.8 +/- 9.5 for peak vertical
      force (PVF) and 9.3 +/- 3.1 for peak vertical impulse (VI). Mean postoperative
      GRFs for all dogs were 40.4 +/- 5.0 for PVF and 14.1 +/- 1.9 for VI. CONCLUSIONS:
      No statistically significant relationship was found between postoperative TPA and
      GRFs after TPLO > or = 4 months after surgery, where the postoperative angle was
      between 0 and 14 degrees. No significant relationship was found between the
      preoperative TPA and postoperative function. CLINICAL RELEVANCE: Limb function in
      Labrador Retrievers was not affected by postoperative TPA and re-operation for
      cases with a postoperative TPA between 0 and 14 degrees is not recommended.

PMID- 16635012
TI  - Outcomes of intrahepatic portosystemic shunts occluded with ameroid constrictors
      in nine dogs and one cat.
AB  - OBJECTIVE: To report outcome after ameroid constrictor (AC) use for single
      intrahepatic portosystemic shunts (IPSS). STUDY DESIGN: Retrospective study.
      ANIMALS: Nine dogs and 1 cat. METHODS: Medical records (1999-2003) of dogs and
      cats with surgically confirmed IPSS were reviewed. Recorded data was: breed, sex,
      weight, age at surgery, clinical signs, serum biochemical and hematologic data,
      shunt anatomy, AC size, hospitalization, complications, and owner perception of
      their animal's response to surgery. Owners were contacted twice postoperatively
      (between 20 and 75 months) and asked to complete a simple questionnaire. RESULTS:
      With this technique, complication rate was low and postligation neurologic
      dysfunction was not observed. In the cat and 7 dogs, clinical signs attributed to
      IPPS resolved and animals were fed a non-prescription diet without medication.
      One dog died suddenly 18 months after surgery from causes unrelated to hepatic
      disease. One dog was euthanatized 23 months after surgery because of repeated,
      increasingly refractory episodes of hepatic encephalopathy. CONCLUSION: AC
      provides a safe and effective method for occlusion of some IPPS. CLINICAL
      RELEVANCE: AC should be considered for occlusion of some IPPS in dogs and cats.

PMID- 16635013
TI  - An in vitro comparison of two suture intervals using braided absorbable loop
      suture in the equine linea alba.
AB  - OBJECTIVE: To compare bursting strength and failure modes of ventral median
      abdominal incisions closed with loop suture in a simple continuous pattern using
      two different suture-bite intervals. STUDY DESIGN: In vitro experiment. SAMPLE
      POPULATION: Equine cadavers (n=14; weighing >318 kg; postmortem interval <2
      hours). METHODS: A template was used to make a 25 cm incision with suture
      interval and bite size of either 1.0 cm x 1.5 cm or 1.5 cm x 1.5 cm. A 200 L
      polyurethane bladder was inserted within the abdomen and insufflated to create
      abdominal wall tension. Celiotomies were closed with a #2 braided lactomer 9-1
      continuous pattern with a loop suture. Deviation from the linea, closure time
      (minutes), total suture length (cm), suture length to wound ratio (SL:WL),
      bursting pressure (mm Hg), and failure modes (fascial or suture) were compared
      between groups using a Mann-Whitney U test. Significance was set at P<.05.
      RESULTS: No significant differences were identified between closing time, total
      suture length used, SL:WL, bursting pressure, or failure mode. Fascial failure
      was the main failure mode for both techniques; suture failure occurred rarely and
      knot failure did not occur. CONCLUSION: Based on the overall bursting pressure
      and failure mode, #2 braided lactomer loop suture placed in a continuous pattern
      should provide sufficient security for closure of the equine linea alba during
      recovery and the immediate postoperative period. CLINICAL RELEVANCE: Although
      there were no significant differences in the 2 patterns evaluated, the 1.5 cm x
      1.5 cm pattern may have potential advantages for closure time, less total suture
      remaining in the wound, and strength.

PMID- 16635015
TI  - Melatonin inhibits both ER alpha activation and breast cancer cell proliferation
      induced by a metalloestrogen, cadmium.
AB  - Cadmium (Cd) is a heavy metal affecting human health both through environmental
      and occupational exposure. There is evidence that Cd accumulates in several
      organs and is carcinogenic to humans. In vivo, Cd mimics the effect of estrogens
      in the uterus and mammary gland. In estrogen-responsive breast cancer cell lines,
      Cd stimulates proliferation and can also activate the estrogen receptor
      independent of estradiol. The ability of this metalloestrogen to increase gene
      expression in MCF7 cells is blocked by anti-estrogens suggesting that the
      activity of these compounds is mediated by ER alpha. The aims of this work were
      to test whether melatonin inhibits Cd-induced proliferation in MCF7 cells, and
      also to study whether melatonin specifically inhibits Cd-induced ER alpha
      transactivation. We show that melatonin prevents the Cd-induced growth of
      synchronized MCF7 breast cancer cells. In transient transfection experiments, we
      prove that both ER alpha- and ER beta-mediated transcription are stimulated by
      Cd. Melatonin is a specific inhibitor of Cd-induced ER alpha-mediated
      transcription in both estrogen response elements (ERE)- and AP1-containing
      promoters, whereas ER beta-mediated transcription is not inhibited by the pineal
      indole. Moreover, the mutant ER alpha-(K302G, K303G), unable to bind calmodulin,
      is activated by Cd but becomes insensitive to melatonin treatment. These results
      proved that melatonin inhibits MCF7 cell growth induced by Cd and abolishes the
      stimulatory effect of the heavy metal in cells expressing ER alpha at both ERE
      luc and AP1-luc sites. We can infer from these experiments that melatonin
      regulates Cd-induced transcription in both ERE- and AP1 pathways. These results
      also reinforce the hypothesis of the anti-estrogenic properties of melatonin as a
      valuable tool in breast cancer therapies.

PMID- 16635016
TI  - Melatonin effect on bone metabolism in rats treated with methylprednisolone.
AB  - The present study was undertaken to examine the effect of melatonin (25 microg/mL
      of drinking water, about 500 microg/day) on a 10-wk long treatment of male rats
      with methylprednisolone (5 mg/kg s.c., 5 days/wk). Bone densitometry and
      mechanical properties, calcemia, phosphatemia and serum bone alkaline phosphatase
      activity and C-telopeptide fragments of collagen type I (CTX) were measured. Both
      melatonin and methylprednisolone decreased significantly body weight (BW) and the
      combination of both treatments resulted in the lowest BW values found.
      Consequently, all results were analyzed with BW as a covariate.
      Densitometrically, methylprednisolone augmented bone mineral content (BMC), bone
      area (BA) and bone mineral density (BMD) in the entire skeleton, BMC in cortical
      bone, and BMC and BMD in trabecular bone. Melatonin increased BMC and BA in whole
      skeleton and BMC and BMD in trabecular bone. For BMC and BA of whole skeleton,
      BMC of cortical bone, and BMC and BMD of trabecular bone, the combination of
      glucocorticoids and melatonin resulted in the highest values observed. Femoral
      weight of rats receiving methylprednisolone or melatonin increased significantly
      and both treatments summated to achieve the greatest effect. In femoral
      biomechanical testing, methylprednisolone augmented ultimate load and work to
      failure significantly. Rats receiving the combined treatment of
      methylprednisolone and melatonin showed the highest values of work to failure.
      The circulating levels of CTX, an index of bone resorption, decreased after
      methylprednisolone or melatonin, both treatments summating to achieve the lowest
      CTX values found. Serum calcium increased after methylprednisolone and serum
      phosphorus decreased after treatment with methylprednisolone or melatonin while
      serum bone alkaline phosphatase levels remained unchanged. The results are
      compatible with the view that low doses of methylprednisolone or melatonin
      decrease bone resorption and have a bone-protecting effect.

PMID- 16635017
TI  - Microarray analysis of transcription factor gene expression in melatonin-treated
      human peripheral blood mononuclear cells.
AB  - The existence of specific melatonin-binding sites in lymphoid cells led to the
      discovery of signal transduction pathway for melatonin in human lymphocytes and
      immunomodulatory role of melatonin in immune cells. In recent years,
      transcriptional regulation of melatonin on various transcription factors has been
      demonstrated. Therefore, this study was designed to assess by cDNA microarray
      analysis the regulatory effects of melatonin on transcription factors in human
      peripheral blood mononuclear cells (PBMCs). Forty-six genes were upregulated and
      23 were downregulated more than twofold in melatonin-treated PBMCs. Of the more
      than twofold upregulated transcription factor genes, homeo box A4 (HOXA4),
      forkhead box O1A (FOXO1A), transcription elongation factor B (SIII), polypeptide
      3 (TCEB3), and peroxisome proliferative activated receptor delta (PPARD) were
      identified. Of the more than twofold downregulated genes, PHD finger protein 15
      (PHF15) and zinc finger protein 33a (ZNF33A) were identified. In summary,
      identification of these genes by cDNA microarray analysis in response to
      melatonin administration may provide a foundation for further studies on the
      function of melatonin in human PBMCs.

PMID- 16635018
TI  - The protective effect of melatonin on ischemia-reperfusion injury in the groin
      (inferior epigastric) flap model in rats.
AB  - Inadequate blood perfusion and ischemia-reperfusion (I/R) injury in the surgical
      skin flap are believed to be the major factors that cause harmful changes within
      the tissue and vasculature, resulting in flap necrosis. Reactive oxygen radical
      species (ROS), in part, are believed to play an important role in this injury.
      Melatonin, in many physiological conditions, has been shown to have direct and
      indirect antioxidative effects and free-radical-scavenging properties. Therefore,
      it may have a beneficial effect on I/R-induced flap injury. In this study, the
      possible protective effects of melatonin were investigated in I/R injury of rat
      epigastric (axial pattern) flaps. Ischemia was achieved for 12 h by occlusion of
      inferior epigastric artery. Melatonin or vehicle was administered 1 h before flap
      elevation and was continued for 6 days after ischemia. I/R injury elevated
      malondialdehyde (MDA), an end product of lipid peroxidation, and nitric oxide
      (NO) levels while the glutathione (GSH) content was reduced. Myeloperoxidase
      (MPO) activity, which is known to be related to tissue neutrophil accumulation,
      was found to be statistically higher in the I/R group when compared with the sham
      group. Administration of melatonin significantly decreased MDA, NO and MPO levels
      and elevated the GSH content. Moreover, melatonin reduced the flap necrosis area,
      which was determined using a planimetric method. In conclusion, melatonin, a
      potent scavenger of free radicals, plays a major role in preventing the inferior
      epigastric arterial I/R-induced flap necrosis, based on planimetric flap survival
      and biochemical results. The beneficial effects of melatonin in I/R injury
      implies the involvement of free radicals in flap damage.

PMID- 16635019
TI  - Effect of melatonin and diazepam on the dissociated circadian rhythm in rats.
AB  - The main structures involved in the circadian system in mammals are the
      suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN contain multiple
      autonomous single-cell circadian oscillators that are coupled among themselves,
      generating a single rhythm. However, under determined circumstances, the
      oscillators may uncouple and generate several rhythmic patterns. Rats exposed to
      an artificially established 22-h light-dark cycle (T22) express two stable
      circadian rhythms in their motor activity that reflect the separate activities of
      two groups of oscillators in the morphologically well-defined ventrolateral and
      dorsomedial SCN subdivisions. In the experiments described in this paper, we
      studied the effect of melatonin and diazepam (DZP) administration in drinking
      water on the dissociated components of rat motor activity exposed to T22, to
      deduce the possible mechanism of these drugs on the circadian system. In order to
      suppress the endogenous circadian rhythm of melatonin, in some of the rats the
      pineal gland or the superior cervical ganglia were removed. The results show that
      melatonin or DZP treatment increased the manifestation of the light-dependent
      component to the detriment of the manifestation of the non-light-dependent
      component and that melatonin, but not DZP, shortens the period of the non-light
      dependent component. These findings suggest that both DZP and melatonin favor
      entrainment to external light, and that melatonin could also act on the SCN,
      producing changes in the period of the circadian cycle.

PMID- 16635020
TI  - Inhibitory effect of melatonin on diquat-induced lipid peroxidation in vivo as
      assessed by the measurement of F2-isoprostanes.
AB  - Melatonin is a powerful antioxidant and free radical scavenger. A large body of
      in vivo and in vitro evidence shows that melatonin effectively inhibits membrane
      lipid peroxidation; this damage was based on the measurement of malondialdehyde
      and/or 4-hydroxynonenal levels. In the current study, for the first time using a
      more sensitive and specific biomarker, i.e. F2-isoprostanes, we investigate the
      effect of melatonin on diquat-induced lipid peroxidation in Fischer 344 rats.
      When diquat (40 mg/kg body weight) was intraperitoneally injected into rats, the
      levels of liver F2-isoprostanes were significantly increased at 1, 3, and 6 hr
      while plasma free F2-isoprostanes concentrations were augmented at 3, 6, and 12
      hr after administration of the toxin. In addition, the plasma alanine
      aminotransferase activity level was measured as a parameter of hepatoxicity; the
      activity of this enzyme was augmented at 3, 6, and 12 hr after diquat
      administration when compared with levels of this constituent in untreated control
      rats. Pretreatment with melatonin (20 mg/kg) 30 min before diquat administration
      resulted in a significant reduction in both tissue and plasma F2-isoprostanes
      levels, and plasma alanine aminotransferase activity. These findings, using a
      sensitive and specific index of lipid peroxidation, show that the hepatoxicity of
      diquat, at least partially, is a consequence of reactive oxygen species-induced
      lipid damage. Melatonin's protective effects likely relate to its direct free
      radical scavenging ability and/or due to other antioxidative processes induced by
      the indole.

PMID- 16635021
TI  - Melatonin enhances alkaline phosphatase activity in differentiating human adult
      mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and
      the MEK/ERK (1/2) signaling cascade.
AB  - The goals of this study were to determine (a) if melatonin enhances human adult
      mesenchymal stem cell (hAMSC) differentiation into osteoblasts as assessed by
      measuring alkaline phosphatase (ALP) enzyme activity, and (b) identify potential
      signal transduction pathways that mediate this process. ALP activity
      significantly increased in hAMSCs following a 10-day incubation in osteogenic
      medium, relative to hAMSCs incubated in basal growth medium alone. Melatonin (50
      nm), added in combination with the osteogenic medium, significantly increased ALP
      activity relative to osteogenic medium alone. Co-exposure of hAMSCs to osteogenic
      medium supplemented with melatonin and either pertussis toxin or the melatonin
      receptor antagonists, luzindole or 4P-PDOT (MT2 receptor selective), inhibited
      the melatonin-induced increase in ALP activity, indicating the involvement of
      melatonin receptors, in particular, MT2 receptors. Assessment of melatonin
      receptor function following exposure to osteogenic medium containing either
      vehicle or melatonin produced dichotomous results. That is, if the
      differentiation of hAMSCs into an osteoblast was induced by osteogenic medium
      alone, then 2-[125I]-iodomelatonin binding and melatonin receptor function
      increased. However, examination of melatonin receptor function following chronic
      melatonin exposure, an exposure that resulted in a 50% enhancement in ALP
      activity, revealed that these receptors were desensitized. This was reflected by
      a complete loss in specific 2-[125I]-iodomelatonin binding as well as melatonin
      efficacy to inhibit forskolin-induced cAMP accumulation. Further characterization
      of the mechanisms underlying melatonin's effects on these differentiation
      processes revealed that MEK (1/2) and ERK (1/2), epidermal growth factor
      receptors, metalloproteinase and clathrin-mediated endocytosis were essential
      while PKA was not. Our results are consistent with a role for melatonin in
      osteoblast differentiation. If so, then, the decrease in plasma melatonin levels
      observed in humans during late adulthood may further enhance susceptibility to
      osteoporosis.

PMID- 16635022
TI  - Urinary metabolites and antioxidant products of exogenous melatonin in the mouse.
AB  - Exogenous melatonin is widely used for sleep disorders and has potential value in
      neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is
      described for the determination of melatonin and six metabolites in mouse urine
      by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin,
      N1-acetyl-5-methoxykynuramine (AMK), N1-acetyl-N2-formyl-5-methoxykynuramine
      (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination
      of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and
      cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5
      pmol, depending on the metabolite. Following oral administration of melatonin to
      mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose),
      6-HMEL (37.1%) and NAS (3.1%) comprising >90% of the total metabolites; AMK and
      AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose,
      which is >100 times more than the AMK/AFMK pathway, and comprises >5% of the
      melatonin-related material detected in mouse urine. 3-HMEL was largely found as a
      sulfate conjugate. These studies establish sensitive assays for determination of
      six melatonin metabolites in mouse urine and confirm the potential for
      antioxidant activity of melatonin through the identification in vivo of AMK and
      AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen
      species.

PMID- 16635023
TI  - Preparation and identification of anti-melatonin monoclonal antibodies.
AB  - Anti-melatonin monoclonal antibodies (MAbs) of high titer were prepared by
      coupling melatonin to bovine serum albumin with formaldehyde and by immunizing
      BALB/c mice with multifocal intradermal injections and by fusing high titer
      antibody producing spleen cells with myeloma cells of SP2/0 origin. Five MAbs
      were selected for further characterization as classes and subclasses. After four
      successive limiting dilutions, antibodies were produced by these five clones with
      high affinities ranging from 10(9) to 10(11)/m. These clones were found to be of
      the immunoglobulin Ig G1 and IgG(2b) subclass with kappa light chain. A
      systematic study of cross-reactions with seven compounds (indole, aromatic and
      imidazole derivatives) showed that the antibody had a high specificity for
      melatonin, low reactivity with 6-hydroxymelatonin and N-acetyl-5
      hydroxytryptamine, and no detectable reactivity with tryptamine, l-tryptophan, 5
      methoxytryptamine and N-acetyl-L-tryptophan. The roles of the indole nucleus and
      the side chain in the determination of the antigenic properties of the molecule
      are discussed. One of the MAbs, 4C9D7, was used to establish a competitive enzyme
      linked immunosorbent assay for the detection of melatonin in supernatant.

PMID- 16635024
TI  - Regression of an esophageal ulcer using a dietary supplement containing
      melatonin.

PMID- 16635025
TI  - Light pollution, melatonin suppression and cancer growth.

PMID- 16635026
TI  - Routine isotropic computed tomography scanning of the abdomen and pelvis.
AB  - For 30 years, abdominal CT has been imaged and reviewed in the axial plane. It is
      now possible to carry out isotropic imaging of the whole abdomen and pelvis using
      a 40-channel scanner. This allows creation of coronal and sagittal reformats with
      the same image quality as the axial images. In this study, we present our
      experience of reviewing routinely coronal and, occasionally, sagittal reformats.
      We discuss situations where these nonaxial reformats are most beneficial.

PMID- 16635027
TI  - Primary gastrointestinal lymphomas: a radiological-pathological review. Part 2:
      Small intestine.
AB  - Primary lymphoma of the small intestine is a heterogeneous group of diseases
      reflected in its protean imaging features. This review illustrates the widespread
      appearances seen on imaging methods (primarily CT and barium studies) with
      pathological correlation.

PMID- 16635028
TI  - Coronary artery anomalies diagnosed by magnetic resonance angiography.
AB  - Coronary artery anomalies are uncommon entities that may be associated with
      sudden death. Because of its 2-D projection imaging nature, conventional X-ray
      coronary angiography may not accurately delineate the origins and course of
      aberrant coronary arteries with respect to the great vessels. Non-invasive, cross
      sectional imaging techniques such as coronary CT angiography and magnetic
      resonance angiography are increasingly used in clinical practice to diagnose
      coronary artery anomalies. Although this study reviews coronary artery anatomy
      and selected anomalies as seen with true fast imaging with steady-state
      precession magnetic resonance angiography, the information provided is equally
      applicable to electrocardiogram-gated coronary CT angiography.

PMID- 16635029
TI  - Preoperative ultrasound-guided fine-needle aspiration cytology for axillary
      staging in breast carcinoma.
AB  - Axillary lymph node (ALN) status is considered to be the single most important
      prognostic indicator in patients with breast cancer. It can be assessed by
      various radiological, pathological and surgical techniques, the most accurate
      being histological examination of lymph nodes after axillary lymph node
      dissection (ALND). This prospective study was conducted to assess the feasibility
      and diagnostic accuracy of preoperative ultrasound (US) and ultrasound-guided
      fine-needle aspiration cytology (USG-FNAC) of ALN in patients with breast cancer.
      Thirty patients with FNAC-proven breast cancer, planned for definitive surgery
      with axillary clearance, were included in this study. Ultrasonographic evaluation
      of the axillae of these patients was conducted for alterations in size, shape,
      contour and cortical morphology of lymph nodes that could reflect presence of
      underlying metastases. Ultrasound-guided fine-needle aspiration cytology of the
      ALN was done in 24 of these patients. These findings were evaluated, with the ALN
      status determined by histological examination after ALND. Out of the 30 patients,
      eight had T(1), 16 had T(2), five had T(3), and one had T(4) lesions. Ultrasound
      evaluation of the ALN had a sensitivity of 86.3%, a specificity of 41.6%, a
      positive predictive value of 79%, a negative predictive value of 50% and a
      diagnostic accuracy of 73.3%. Sensitivity of USG-FNAC was 78.95%, specificity was
      100%, positive predictive value was 100%, negative predictive value was 55.56%
      and diagnostic accuracy was 83.33%. Our study concludes that preoperative USG
      FNAC of ALN is a simple, minimally invasive, easily available and reliable
      technique for the initial determination of ALN status in patients with breast
      cancer. Those who are USG-FNAC positive can be directed towards ALND straight
      away, and only those who are USG-FNAC negative should be considered for sentinel
      lymph node biopsy. This will save considerable operating time, especially where
      facilities for sentinel lymph node biopsy (costly dye, gamma camera, nuclear
      medicine facilities) are restricted or not available.

PMID- 16635030
TI  - Intrinsic measurement bias on computed tomography scout view is unpredictable:
      Computed tomography pelvimetry using a phantom.
AB  - Our aim was to determine the degree of bias in CT scanogram measurements. We
      obtained standard lateral and anteroposterior (AP) pelvimetry scanograms of a
      phantom pelvis after placing ball bearings or aluminium rods to mark bony
      landmarks. Computed tomography pelvimetry was carried out at the manufacturer
      recommended table height on two commercial CT scanners and at 10-mm increments up
      to 50 mm above and below this height. The AP inlet, AP outlet, interspinous
      distance and transverse diameters were each measured three times for each
      scanogram. The true measurements were obtained directly from the disassembled
      phantom. Bias was defined as the difference between the CT measurement and the
      true measurement. Observer error was negligible. The transverse diameter was
      overestimated at high table positions and underestimated at low table positions
      on both scanners (+6 to -10 mm). After correcting for geometric distortion, up to
      6 mm bias was still present. The point at which no bias occurred was different
      for each scanner and did not correspond to the manufacturers' recommended table
      height. The outlet was overestimated on both scanners by up to 5 mm. The true
      inlet measurement was overestimated by 1.2 mm. The interspinous distance was
      minimally underestimated on both scanners. The measurements on CT scanogram were
      underestimated or overestimated in an inconsistent and unpredictable fashion,
      varying from one type of measurement to another and from CT scanner to CT
      scanner. This has implications for the accuracy and clinical utility of
      measurements obtained from a CT scanogram.

PMID- 16635031
TI  - Managing peripherally inserted central catheter-related venous thrombosis: How I
      do it.
AB  - Imaging-guided insertion of central venous catheters, either in the form of a
      peripherally inserted central catheter (PICC) or through a subclavian or a
      jugular approach, is becoming the preferred method of acquiring long-term venous
      access for a variety of therapeutic purposes. The most significant complication
      from central venous catheters is thrombosis of the catheterized vein. Venous
      thrombosis related to the insertion of PICC lines is conventionally treated with
      line removal followed by anticoagulation. Direct thrombolysis with urokinase,
      using the lumen of the PICC line to facilitate the insertion of the infusion
      catheter is a simple, safe and effective treatment option. In this article, we
      describe our experience with this procedure and the technique used.

PMID- 16635032
TI  - Spiral computed tomography-intravenous cholangiography with three-dimensional
      reconstructions for imaging the biliary tree.
AB  - This study aimed to assess the ability of CT-i.v. cholangiography to show the
      perihilar biliary and cystic duct anatomy and to assess the relative performance
      of axial, maximum intensity projection and surface rendered displays. We also
      assessed the correlation between serum bilirubin levels and adequacy of biliary
      opacification. Spiral CT was carried out following infusion of 100 mL of
      Biliscopin in 181 patients with suspected biliary disease. The display of biliary
      anatomy was of high quality, with 91% of patients having good opacification of at
      least first-order bile ducts and 84% having good opacification of at least third
      order right and left hepatic ducts. The quality of biliary opacification
      correlated inversely to serum bilirubin levels, with levels above two to three
      times the normal value being associated with lower rates of good opacification.
      Maximum intensity projection and surface rendered reformats aided anatomical
      interpretation to a similar degree. The relative frequency of types of perihilar
      branching patterns and cystic duct junctional anatomy correlated closely to those
      reported from previous anatomical studies.

PMID- 16635033
TI  - Accelerated partial breast irradiation using interstitial high dose rate iridium
      brachytherapy: Early Australian experience and review of the literature.
AB  - Summary Accelerated partial breast irradiation (APBI) is an evolving new
      technique of adjuvant irradiation in selected women with early-stage breast
      cancer. We developed a pilot programme of APBI in 2000 and report end results in
      seven patients followed for a mean of 42.7 months (range 29-55 months). Good to
      excellent cosmesis and no loco-regional relapse or systemic metastases have
      occurred. The literature related to APBI is reviewed.

PMID- 16635034
TI  - TN/TN glottic carcinoma: a comparison of two fractionation schedules.
AB  - The aim of this paper is the retrospective comparison of
      accelerated/hypofractionated radiotherapy regimen (AHFX) with standard
      fractionation regimen (SFX) for patients with early glottic carcinoma. One
      hundred and forty-five patients with T(1)-T(2) glottic cancer between 1986 and
      1998 were eligible. Before 1992, patients received 60-66 Gy in 30-33 fractions
      over 6-6.5 weeks (SFX) with (60)Co and 6-MV beams. After 1992, patients received
      52.5-55 Gy in 20 fractions over 4 weeks (AHFX) using 6-MV beams. The end-points
      were overall survival, laryngectomy-free survival (LFS), loco-regional control
      and toxicity. One hundred and two were stage T(1)N(0); 43 were stage T(2)N(0).
      Median follow up was 4.9 years. The 5-year overall survival was 78%. Five-year
      loco-regional control in T(1)N(0) patients was higher in AHFX than in SFX group
      (95 vs 75%, P = 0.002). Loco-regional control in T(2)N(0) patients was similar
      for AHFX and SFX (81 vs 80%, P = 0.813). Overall LFS was 88%. T(1)N(0) AHFX
      patients had 5-year LFS of 95% compared with 75% for SFX (P = 0.003). For
      T(2)N(0) AHFX patients, overall LFS was 92% compared with 80% for the SFX group
      (P = 0.291). No grade 4 or 5 late toxicity occurred. One AHFX patient developed
      grade 3 toxicity; two of 51 SFX patients developed grade 2 toxicity versus five
      of 94 AHFX patients. AHFX using 6-MV beams for treatment of early glottic cancer
      resulted in equivalent LFS and toxicity when compared with SFX.

PMID- 16635035
TI  - Update of radiosurgery at the Royal Adelaide Hospital.
AB  - This is an update of the Royal Adelaide Hospital radiosurgery experience between
      November 1993 and December 2004 comprising 165 patients with 168 intracranial
      lesions. Including re-treatment, there were 175 treatment episodes (163
      radiosurgery and 12 stereotactic radiotherapy) at an average of 1.3 per month.
      The commonest lesions were acoustic neuroma (65), arteriovenous malformation
      (58), solitary brain metastasis (23) and meningioma (14). The clinical features,
      treatment details and outcome are described. Our results continue to be well
      within the range reported in the published work. Radiosurgery provides an
      elegant, non-invasive alternative to neurosurgery and conventional external beam
      radiotherapy for many benign and malignant brain tumours.

PMID- 16635036
TI  - Thoracic ventral dural defect: idiopathic spinal cord herniation.
AB  - Thoracic ventral dural defect, and resultant idiopathic spinal cord herniation,
      is a rare but increasingly recognized cause of a chronic progressive thoracic
      myelopathy, particularly in middle-aged women. A neurosurgically confirmed case
      is presented, together with a review of the pathogenesis, clinical presentation,
      imaging features, treatment options and progress of this entity post-treatment.

PMID- 16635037
TI  - Intussusception of the small bowel discovered incidentally by computed
      tomography.
AB  - Three cases of asymptomatic intussusception in adults are reported, discovered
      incidentally during a CT scan of the abdomen. It is being increasingly observed
      in adults, possibly aided by the reformatting capabilities of the new multislice
      CT scanners. It has been documented in children where it is considered to be
      transient and of no clinical significance.

PMID- 16635038
TI  - Magnetic resonance imaging of thickened pituitary stalk proceeding to Langerhans
      cell histiocytosis in a child.
AB  - Magnetic resonance imaging has shown isolated pituitary stalk thickening in
      certain cases of idiopathic or secondary central diabetes insipidus (DI) due to
      infiltrative processes. We present a 4-year-old boy who was initially diagnosed
      as having central DI. The MRI showed isolated pituitary stalk thickening with
      prominent homogeneous contrast enhancement. The remaining findings on MRI were
      within normal limits. The patient's personal and family history and laboratory
      and clinical findings were unremarkable; therefore, he was initially diagnosed as
      having idiopathic DI. Since central DI and isolated pituitary stalk thickening
      may be considered to be the first manifestations of Langerhans cell
      histiocytosis, we decided to follow up the patient. After 5 months, following the
      initial diagnosis, on skeletal X-ray survey, the patient did indeed develop
      multiple lytic skull lesions which, on biopsy, were histologically typical bone
      lesions of Langerhans cell histiocytosis.

PMID- 16635039
TI  - Preoperative embolization of a large vaginal leiomyoma: report of a case and
      review of the literature.
AB  - Leiomyoma of the vagina is a very rare tumour of the lower urogenital tract.
      These slow-growing masses may be asymptomatic or present with pain, dyspareunia
      or urinary symptoms. Rarely, these tumours may present with life-threatening
      haemorrhage. These hypervascular tumours are treated by surgical excision.
      Preoperative embolization therefore may aid in devascularization of these tumours
      before surgical excision. We present the MRI features of a case of vaginal
      leiomyoma, which was managed by preoperative embolization and was then excised in
      toto. To the best of our knowledge, this is the first report where preoperative
      embolization was performed before excision of a vaginal leiomyoma with minimal
      peroperative blood loss.

PMID- 16635040
TI  - Filarial dance in a breast mass on colour Doppler imaging.
AB  - Filarial dance in breast lesions is a very rare entity. It is difficult to show
      the characteristic vigorous movement of the adult worms on static images although
      pulse wave Doppler and colour power Doppler have been used. Filarial dance on
      colour Doppler imaging has not been reported earlier to the best of our
      knowledge.

PMID- 16635041
TI  - Intravenous lobular capillary haemangioma: ultrasound and histology findings.
AB  - Intravenous lobular capillary haemangioma is a rare variant of lobular capillary
      haemangioma. This article describes the ultrasound and histological findings of
      such a lesion.

PMID- 16635044
TI  - Striding forward or getting too big for their boots? The developing role of data
      monitoring committees in clinical trials.

PMID- 16635045
TI  - A potential novel strategy to separate therapeutic- and side-effects that are
      mediated via the same receptor: beta-arrestin2/G-protein coupling antagonists.

PMID- 16635046
TI  - Is 'chemo-fog'/'chemo-brain' caused by cancer chemotherapy?

PMID- 16635047
TI  - Dosage dependent hormonal counter regulation to combination therapy in patients
      with left ventricular dysfunction.
AB  - The present study attempts to assess the efficacy combination therapy for heart
      failure. Genuine dose-response studies on combination therapy are not available
      and published studies involved adding one drug on top of 'usual treatment'.
      Sixteen different dosage combinations of trandolapril and bumetanide was tested
      in a double blind, double placebo-controlled, randomized, multiple cross-over
      study in a 16 times six balanced incomplete Latin square design. Patients
      reported optimal quality of life on the sub maximal dose bumetanide. Bumetanide
      decreased left ventricular function and increased heart rate and plasma
      noradrenaline in a dose dependent manner. Doses of bumetanide of more than 0.5
      mg, given twice daily significantly decreased the quality of life and increased
      diuresis. Weight loss was maximal on 0.5 mg bumetanide twice daily. Trandolapril
      significantly reduced systolic blood pressure with the maximal effect at 0.5 mg
      daily. Both drugs significantly increased renin concentration with a significant
      potentiating interaction. It was not possible to detect beneficial effects of
      combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg
      twice daily based on its effect on quality of life and weight loss. Estimated by
      the reduction in systolic blood pressure the optimal dosage of Trandolapril
      appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be
      given less than the usually recommended dosages. Patients may be treated with a
      low dose loop diuretic, if signs of water retention are present or if symptomatic
      relief is desired.

PMID- 16635048
TI  - Short-term infliximab therapy improves symptoms of psoriatic arthritis and
      decreases concentrations of cartilage oligomeric matrix protein.
AB  - OBJECTIVE: The aim of the current study was to evaluate the short-term effects of
      anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage
      oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage
      destruction. METHODS: Nine consecutive patients with active psoriatic arthritis
      (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured
      and correlated to pre-established disease activity outcome variables: pain as
      assessed by the patient, using the 100 mm visual analogue scale (VAS), duration
      of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC),
      erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS:
      Significant improvements in MGST, VAS, SJC and TJC values were observed after 6
      weeks of therapy. Similar significant improvements were demonstrated in the ACR
      response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP
      decreased significantly over 6 weeks. Serum COMP levels also decreased
      significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1
      after 6 weeks, P < 0.008). CONCLUSION: The results of our study suggest that
      short-term therapy with infliximab leads to decreased COMP levels in patients
      with PsA. COMP seems to be a good candidate for a biomarker reflecting cartilage
      response to this treatment in PsA patients.

PMID- 16635049
TI  - Effect of treatment with nebivolol on parameters of oxidative stress in type 2
      diabetics with mild to moderate hypertension.
AB  - AIM: The aim of this study was to examine the effect of the cadioselective B(1)
      adrenoceptor blocker nebivolol on glycaemic control, lipid profile and markers of
      oxidative stress in patients with type 2 diabetes over a 6-month period. METHODS:
      Twenty-six patients with mild to moderate hypertension (140-160 mmHg systolic, 90
      105 mmHg diastolic) confirmed on 24-h blood pressure monitoring, were treated
      with nebivolol 5 mg daily for 6 months. Total serum cholesterol, triglycerides,
      high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL)
      subfractions, lipid hydroperoxides (LHPs) and total antioxidant capacity (TAC)
      were measured before and after 6 months of treatment. RESULTS: Nebivolol, as
      expected, reduced mean daytime systolic and diastolic pressures on ambulatory
      monitoring (149 +/- 9 to 140 +/- 13 mmHg, P = 0.02 and 84 +/- 7 to 77 +/- 9 mmHg,
      P < 0.001). There were no significant changes in serum cholesterol or
      triglycerides following treatment but a significant increase in HDL cholesterol
      was noted (1.12 +/- 0.19 to 1.25 +/- 0.36 mmol/L, P = 0.008). Patients showed a
      highly significant reduction in TAC from 501 +/- 57 to 422 +/- 29 trolox
      equivalent (P < 0.001). Baseline LHPs were very high and showed no significant
      change over the 6-month period (18.7 +/- 7.4 and 18.7 +/- 10.9 micromol/L). The
      LDL score increased significantly from 1.7 +/- 0.7 to 2.3 +/- 0.7 (P = 0.0002) at
      6 months suggesting a change to a more atherogenic lipid profile. Neither weight
      nor glycaemic control changed during treatment. CONCLUSION: Nebivolol appears to
      be lipid neutral and may even have a positive effect on HDL cholesterol. Despite
      this it may promote the formation of potentially atherogenic LDL subfractions
      possibly as a result of reduced antioxidant defences. Further studies are needed
      to clarify the changes observed in parameters of oxidative stress.

PMID- 16635050
TI  - How high should total pain-relief score be to obviate the need for analgesic
      remedication in acute pain? Estimation using signal detection theory and
      individual-patient meta-analysis.
AB  - BACKGROUND: A pain relief score 50% of the maximum is often used as a clinically
      meaningful outcome in meta-analyses of analgesic trials. This arbitrary value
      requires validation. OBJECTIVE: To determine the optimum pain relief score for
      predicting pain relief sufficient to obviate the need for analgesic remedication
      in acute post-surgical pain. DESIGN: Individual-patient meta-analysis of
      randomized controlled trials and use of signal detection theory to identify the
      optimum cut-off point on the total pain relief score (TOTPAR). Analgesic
      remedication was used as the clinical outcome. DATA SOURCES: Seven parallel
      group, active and placebo-controlled trials of minor analgesics. RESULTS: The
      predictive value of the TOTPAR score [expressed as a percentage of the maximum
      score (%maxTOTPAR)] for remedication was excellent for all the trials. The pooled
      estimate of the area under the receiver operating curve, an index of
      discriminative power, was outstanding 0.96 (95% CI 0.95-0.97). The pooled
      estimate of the optimal %maxTOTPAR for predictive purposes was 44.11 (95% CI
      44.00-44.23). CONCLUSION: The analysis suggests that the arbitrary 50% cut-off
      point TOTPAR score often used in meta-analyses of analgesic trials in dental pain
      is reasonably acceptable. This is different to the 33% cut-off point reported for
      analgesic trials of acute breakthrough cancer pain and some chronic pain states
      such as diabetic neuropathy and postherpetic neuralgia. These differences deserve
      careful consideration when reading reports of analgesic trials and meta-analyses.
      Remedication itself should be considered as the preferred outcome measure for
      analgesic trials.

PMID- 16635051
TI  - Physical and microbiological stability of an extemporaneous tacrolimus suspension
      for paediatric use.
AB  - OBJECTIVE: An extemporaneous suspension of tacrolimus for paediatric use has
      recently been developed but poor bioavailability and erratic plasma
      concentrations were observed during clinical use. It was not clear whether this
      was due to changes in the physical properties of the suspension during storage.
      The aim of this work was to investigate the physical and microbiological
      stability over the recommended 8-week shelf-life of this extemporaneous
      tacrolimus suspension. METHODS: Suspensions (0.5 mg/mL) were custom made by a
      special manufacturer under Good Manufacturing Practice conditions. The procedure
      involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 :
      1) using a mortar and pestle followed by an homogenization step. The particle
      sizes of the suspensions were measured using a MasterSizer. A light microscope
      equipped with polarizers was used to visualize any particle size changes or
      crystal growth. Viable bacterial and fungal contamination was assessed using
      standard colony count techniques on solid media. The suspensions were kept at 22
      26 degrees C and evaluated weekly. RESULTS: The volume mean diameter d((4,3))
      from laser diffraction did not change significantly. Light microscopy did not
      reveal any significant change in particle size or crystal growth. Contamination
      by viable and culturable micro-organisms could not be detected. CONCLUSION: The
      suspension was physically (particle size) and microbiologically stable during the
      8-week study period suggesting other factors including poor dosing could be
      responsible for the pharmacokinetic variation observed during clinical use which
      warrants further investigation.

PMID- 16635052
TI  - The all-powerful and 'happy' drug: the use of steroids among primary care doctors
      in Hong Kong.
AB  - BACKGROUND: Steroids are commonly used, but their prescribing pattern and factors
      associated with their use in the primary care setting are largely unknown.
      METHODS: Using diagnosis and drug data obtained from logbooks submitted by
      participants in the Diploma in Family Medicine course between 1999 and 2004, we
      selected and analysed all patients with a prescription of steroid as well as
      conditions in which it was prescribed. Factors, relating to patients or doctors,
      which could be associated with steroid prescription were recorded for both the
      prescribed and the non-prescribed groups. The results were compared using chi
      square tests. RESULTS: Steroids were prescribed in 7.1% of all patient
      encounters, of which dermatological and respiratory diseases were the most two
      common conditions. Upper respiratory tract infections accounted for a third of
      all respiratory diseases in which steroid was prescribed. Female or 'minor'
      patients (OR 1.16, 95% CI 1.01-1.32 and 1.16, 1.00-1.36 respectively) were more
      likely to be given a steroid and younger doctors (1.52, 1.25-1.86) were more
      likely to prescribe them. CONCLUSION: Some patterns of poor prescribing practice
      were demonstrated in this study. Campaigns by professional bodies may improve
      prescribing among our community doctors and effective public education programmes
      are needed to modify the health beliefs and expectations of the general public.

PMID- 16635053
TI  - Developing and implementing a model for changing physicians' prescribing habits--
      the role of clinical pharmacy in leading the change.
AB  - BACKGROUND AND OBJECTIVE: Budgetary constraints led the Israeli Hillel Yaffe
      Medical Center management to implement policies for reducing expenditure while
      maintaining the quality of care. For this purpose, the pharmacy services
      management developed and implemented a three-tier intervention feedback model for
      changing physicians' prescribing habits, and achieving cost-effective changes in
      antibiotic utilization. METHODS: A prospective drug utilization evaluation was
      conducted to profile antibiotic utilization. The results established a base from
      which a three-tier feedback, evidence-based intervention model was built. This
      model corresponds to the following three hierarchical levels: Level 1 activities
      involved management actions that influenced all levels of staff and concentrated
      mainly on the creation of guidelines. Level 2 activities involved the
      reorganization of the restricted antibiotics prescription authorization system,
      through the co-operation of the clinical pharmacy unit and the hospital infection
      control specialist. Level 3 focussed on clinical pharmacist activities on the
      wards. The model was implemented and assessed in the hospital from June 2002
      until December 2004. RESULTS AND DISCUSSION: Implementation of the model resulted
      in a cumulative decrease of 6,473 i.v. antibiotics daily defined doses (DDDs) and
      a parallel increase in total oral antibiotic DDDs (Table 1). These changes were
      especially notable with high-bioavailability antibiotics and co-amoxiclav, where
      over 2.5 years there was a reduction of 2,472 and 4,752 i.v. DDDs, respectively
      (P < 0.000). The successful implementation of the model resulted in a reduction
      of 375,000 NIS ( approximately 66,190 euro) in pharmacy antibiotic costs,
      equivalent to 10 i.v. DDDs or 570 NIS ( approximately 102 euro) saved per
      clinical pharmacist working day. CONCLUSIONS: Our study demonstrates the
      successful implementation of a three-tier model for changing physicians'
      antibiotic prescribing.

PMID- 16635054
TI  - Malaysian Indians are genetically similar to Caucasians: CYP2C9 polymorphism.
AB  - BACKGROUND: CYP2C9 is one of the major drug metabolizing enzymes for many drugs
      including warfarin, NSAIDs and losartan. It is polymorphic in many populations.
      Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in
      the Malaysian population is lacking. Our objectives were therefore to investigate
      the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays,
      Chinese and Indians in Malaysia. METHOD: Deoxyribonucleic acid was extracted
      using standard lysis methods. Allele specific polymerase chain reaction was
      performed for determination of CYP2C9*1, *2, *3, *4 and *5 variants according to
      Z. Zainuddin, L.K. Teh, A.W.M. Suhaimi, M.Z. Salleh, R. Ismail (2003, Clinica
      Chimica Acta, 336, 97). RESULT: The Chinese had the highest frequency of CYP2C9*1
      (321/330, 97.27%), followed by the Malays and the Indians (402 of 420, 95.71% and
      291 of 330, 88.18%, respectively). CYP2C9*2 was not found in the Chinese.
      CYP2C9*3 were detected in all the three races with the Indians having the highest
      frequency of CYP2C9*3 (9.7%). The Indians had a frequency of CYP2C9*2 and *3
      similar to Tamilians and Caucasians. Two of the Indians had *2/*3 and one had
      *3/*3 genotypes and are likely to be slow metabolizers. No subject with CYP2C9*4
      and *5 were detected in our populations. CONCLUSION: CYP2C9*2 and *3 were
      identified in our population. Indians are similar to Caucasians in terms of
      CYP2C9 genotypes and thus may respond to CYP2C9 substrates differently when
      compared with the Malays and Chinese in Malaysia.

PMID- 16635055
TI  - Can childhood trauma predict response to topiramate in borderline personality
      disorder?
AB  - We report on a woman with borderline personality disorder and a history of
      childhood trauma that showed significant clinical response with low dosage of
      topiramate. We propose that topiramate changed some of the main features of this
      disorder, such as catastrophic reaction to real or imaginary abandonment or
      rejection, improving adaptive functioning. We hypothesize that topiramate might
      facilitate memory extinction, therefore decreasing emotional and behavioural
      reactivity.

PMID- 16635056
TI  - Edaravone inhibits the disease activity in rheumatoid arthritis.
AB  - A male patient with rheumatoid arthritis (RA) developed acute stroke and was
      treated with the free radical scavenger, edaravone. Polyarthralgia improved with
      a reduction in serum C-reactive protein concentration soon after the start of
      edaravone administration. The disease activity score 28 (DAS28) also decreased.
      Edaravone appears to be effective for the control of RA. The usefulness of this
      potentially novel therapeutic agent should be tested in a well designed
      randomized controlled trial.

PMID- 16635057
TI  - Feasibility studies on division of fixed dose combinations of anti-tubercular
      drugs: an improvement in the tuberculosis therapy.

PMID- 16635059
TI  - The epidemiology of Argulus spp. (Crustacea: Branchiura) infections in stillwater
      trout fisheries.
AB  - Problem infections caused by species of the crustacean ectoparasite, Argulus, in
      UK stillwater trout fisheries appear to have increased in recent years. A cross
      sectional study of 77 such fisheries was conducted to establish the perceived
      problem and the extent and severity of this problem, and to identify associated
      risk factors. An interview-based study was conducted in 2001 using a standardized
      questionnaire based on the management and infection status of each fishery in the
      previous year. Logistic regression was used to identify potential risk factors.
      Argulus spp. were perceived to cause economic losses in infected fisheries
      through a reduction in the number of anglers due to reduced aesthetic appeal and
      catchability of fish. Of the sites studied, 29% experienced such a problem
      infection in 2000. Argulus foliaceus was identified in all but one case and was
      found to be widely distributed throughout the UK. The remaining case was
      identified as Argulus coregoni. Three risk factors were associated with problem
      infections: the presence of an algal bloom, slow rates of stock turnover and
      whether water level dropped by <1 m during the summer months.

PMID- 16635060
TI  - Detection of infectious haematopoietic necrosis virus and infectious salmon
      anaemia virus by molecular padlock amplification.
AB  - A new method for the molecular detection of the fish pathogens, infectious
      haematopoietic necrosis virus (IHNV) and infectious salmon anaemia virus (ISAV),
      is described. By employing molecular padlock probe (MPP) technology combined with
      rolling circle amplification (RCA) and hyperbranching (Hbr), it is possible to
      detect RNA target sequence from these viruses at levels comparable with those
      detected by the polymerase chain reaction (PCR), but without prior reverse
      transcription. The use of MPP technology combined with RCA and Hbr for the
      detection of IHNV and ISAV in fish exhibited selectivity comparable with that of
      PCR while potentially reducing the time and cost required for analysis. The
      method described was used to detect as few as 10(4) DNA oligonucleotide targets
      and was sequence-specific at the single base level. Viral RNA could be detected
      directly, either alone or in the presence of non-viral RNA from fish tissue. This
      technology is applicable for detecting a variety of microbes, in addition to IHNV
      and ISAV, and is ideal for further integration into a biosensor platform for on
      site diagnosis of pathogen infection in fish.

PMID- 16635061
TI  - Quantitative expression (Walbaum) of immunological factors in rainbow trout,
      Oncorhynchus mykiss (Walbaum), after infection with either Flavobacterium
      psychrophilum, Aeromonas salmonicida, or infectious haematopoietic necrosis
      virus.
AB  - To further enhance our understanding of immunological gene expression in rainbow
      trout, Oncorhynchus mykiss, after infection with naturally occurring pathogens, a
      series of probes and primers were developed for the quantification of immune
      factors. Separate groups of specific-pathogen-free rainbow trout were infected
      with either Flavobacterium psychrophilum, Aeromonas salmonicida or infectious
      haematopoietic necrosis virus (IHNV). Three different concentrations of each
      pathogen were used and samples from infected and mock-infected fish were taken at
      either 1 or 5 days after infection. Ten fish were sampled at each time point for
      individual sections of liver, spleen and head kidney. Organ specimens from five
      of the fish were used to re-isolate and quantify the pathogen at the time the
      samples were taken. Total RNA was extracted from the organs of the remaining five
      animals. Using real-time polymerase chain reaction with fluorescent-labelled
      probes, the RNA from these organs was examined for the level of expression of the
      following immunological factors; an interferon related protein (MX-1),
      interleukin-8 (IL-8), the cytotoxic T-cell marker CD-8 and complement factor C3
      (C3). They were also measured for the level of beta-actin, which was used as a
      standardization control for cellular RNA expression. Infection with IHNV produced
      the greatest change in expression level for all the immunological related factors
      examined in this study. IHNV elicited the best dose response profile, which was
      typically seen at 5-days post-infection for MX-1, C3, IL-8 and CD-8. Infection
      with A. salmonicida and F. psychrophilum showed elevated, but variable expression
      levels for several of the genes tested.

PMID- 16635062
TI  - Apoptosis in Ichthyophthirius multifiliis is associated with expression of the
      Fas receptor of theronts.
AB  - The expression of type I membrane Fas receptors on the surface of
      Ichthyophthirius multifiliis (Ich) theronts and the possible association between
      Fas expression and theront apoptosis induced by the immune antibody was examined.
      Fas receptors were detected on the theront surface using fluorescein
      isothiocyanate-conjugated mouse monoclonal antibody against Fas. Fas-positive
      theronts significantly increased with time during in vitro incubation and with
      increasing theront concentration. Furthermore, the immune cutaneous antibody
      induced theront apoptosis; however, Fas ligand did not. A highly significant
      correlation was noted between theront Fas expression and immune cutaneous
      antibody-induced theront apoptosis. Numbers of apoptotic theronts increased with
      increasing number of Fas-positive theronts. The data indicated that theront
      apoptosis induced by immune cutaneous antibody appears to be positively
      correlated with the expression of Fas on the surface of Ich theronts.

PMID- 16635063
TI  - Longitudinal study of a natural outbreak of heart and skeletal muscle
      inflammation in Atlantic salmon, Salmo salar L.
AB  - Heart and skeletal muscle inflammation (HSMI) is a transmissible disease of
      farmed Atlantic salmon, Salmo salar L. It is characterized by significant epi-,
      endo- and myocarditis, as well as myositis, particularly involving red skeletal
      muscle. The aetiology of HSMI is currently unresolved, though a viral cause is
      suspected. Since its discovery in 1999, HSMI has become an increasing problem for
      the Norwegian farming industry, with some farms experiencing yearly outbreaks and
      subsequent economic losses. In the present study an Atlantic salmon farm was
      studied from December 2003 to April 2005. Samples from apparently healthy as well
      as clinically diseased fish were collected monthly and examined
      histopathologically. The first fish to be diagnosed with HSMI was sampled in May,
      8 months after transfer to sea. A clinical outbreak of HSMI followed in June,
      when all fish in the sample had lesions consistent with HSMI. Subsequent samples
      revealed that cardiac lesions decreased in severity 2 months after the start of
      the outbreak, but that multiple foci of cellular infiltration and necrosis
      persisted throughout the year. There appeared to be a shift in lesion location
      from being most severe in the compact myocardium in early stages of disease to a
      greater involvement of the atrium and spongy layer of the ventricle in later
      samples. Late samples also showed increased fibrosis of cardiac tissue. In
      conclusion, HSMI appears to be a severe disease with elevated mortality,
      morbidity close to 100% and prolonged duration.

PMID- 16635064
TI  - Genetic diversity of Flavobacterium columnare isolated from fish collected from
      warm and cold water.

PMID- 16635065
TI  - Adherence of Lactococcus garvieae to the intestinal and brain gangliosides of the
      yellowtail, Seriola quinqueradiata Temminck and Schlegel.

PMID- 16635066
TI  - Treatment of thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and
      microangiopathic haemolytic anaemia, was almost universally fatal until the
      introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical
      studies, daily PE has become the first-choice therapy since 1991. Recent findings
      may explain its effectiveness, which may include, in particular, the removal of
      anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers
      and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on
      currently available data, the favoured PE regimen is daily PE [involving
      replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma
      (FFP)] until remission. Adverse events of treatment are mainly related to central
      venous catheters. The potential reduction of plasma related side-effects, such as
      transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by
      use of solvent-detergent treated (S/D) plasma instead of FFP is not established
      by controlled clinical studies. Uncontrolled clinical observations and the
      hypothesis of an autoimmune process in a significant part of the patients with
      acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with
      corticosteroids. Other immunosuppressive treatments are not tested in controlled
      trials and should be reserved for refractory or relapsing disease. There is no
      convincing evidence for the use of antiplatelet agents. Supportive treatment with
      transfusion of red blood cells or platelets has to be evaluated on a clinical
      basis, but the transfusion trigger for platelets should be very restrictive.
      Further controlled, prospective studies should consider the different
      pathophysiological features of thrombotic microangiopathies, address the
      prognostic significance of ADAMTS13 and explore alternative exchange fluids to
      FFP, the role of immunosuppressive therapies and of new plasma saving approaches
      as recombinant ADAMTS13 and protein A immunoadsorption.

PMID- 16635067
TI  - Unique donor-suitability issues.
AB  - On occasion, there arise questions or situations involving blood-donor
      eligibility determination, which are not adequately addressed by the existing
      regulations and standards. In such instances, even the most experienced blood
      collector may be uncertain regarding the best course of action and unable to find
      adequate guidance in the standard blood banking references, regulations and
      literature. In order to examine this area in greater depth, the American
      Association of Blood Banks (AABB) sponsored a short topic session on 'Unique
      Donor Suitability Issues' at their 2004 annual meeting. The invited speakers were
      four seasoned physician medical directors, with a combined experience of over 40
      years in blood collection at both regional and national levels. They were tasked
      with identifying and researching problematic areas in donor-suitability
      determination, and suggesting an overall approach to dealing with such issues.
      They determined that three of the most problematic areas of eligibility
      evaluation included donors with: (1) disabilities, (2) disorders of haemostasis,
      and (3) trans-sexual, homosexual and other unusual gender-related issues. Each of
      these topics was presented in a 10-min lecture, followed by an open format
      consisting of audience participation and panel discussion by the speakers. The
      session was additionally enhanced by a representative of the United States Food
      and Drug Administration (FDA) who participated as a member of the audience. This
      review presents the contents of the short topic session in an expanded form.

PMID- 16635068
TI  - Pall leukotrap affinity prion-reduction filter removes exogenous infectious
      prions and endogenous infectivity from red cell concentrates.
AB  - BACKGROUND AND OBJECTIVES: Three recent probable cases of transmission of a
      variant of human Creutzfeldt-Jakob disease (vCJD) through blood transfusion
      suggest that the disease can be transmitted through transfusion of blood
      components from presymptomatic blood donors. In this study, we investigated the
      performance of a new filter for reducing the levels of infectious prions
      (PrP(Sc)) from red cell concentrates (RCC). MATERIALS AND METHODS: Endogenous
      Infectivity: A pool of 500 ml of whole blood was collected from 263K-strain
      scrapie-infected hamsters into an anticoagulant, processed into non-leucoreduced
      RCC (NL-RCC), and then passed through a prion-reduction filter. Pre- and
      postfiltration samples were tested for PrP(Sc) by Western blot and infectivity by
      inoculation of healthy hamsters. Results of the endogenous infectivity study
      after 200 days post-inoculation are discussed. Exogenous (Spiking) Study: Scrapie
      infected hamster brain homogenates containing PrP(Sc) were added to human RCC and
      then filtered. Levels of PrP(Sc) were determined by Western blot assay. The
      effect of prior leucodepletion of 'spiked' RCC on PrP(Sc) removal by the prion
      removal filter was also assessed. RESULTS: In the endogenous infectivity study,
      at 200-day observation time, the prefiltered RCC transmitted disease to six of
      the 187 hamsters, whereas the filtered RCC did not transmit disease to any of 413
      animals, P = 0.001. The prion filter also significantly reduced the concentration
      of leucocytes in the RCC by about 4 logs, P < 0.05. In the exogenous (spiking)
      study, the level of PrP(res) was significantly reduced in RCC P < 0.05. Prior
      leucodepletion of the RCC with a leucoreduction filter did not significantly
      reduce the concentration of exogenously spiked PrP(Sc), P > 0.05. CONCLUSION: The
      use of this new prion-reduction filter should reduce the risk of vCJD
      transmission through transfusion of RCC, the most widely transfused blood
      component.

PMID- 16635069
TI  - Fluorescence quencher improves SCANSYSTEM for rapid bacterial detection.
AB  - BACKGROUND AND OBJECTIVES: The optimized scansystem could detect contaminated
      platelet products within 24 h. However, the system's sensitivity was reduced by a
      high fluorescence background even in sterile samples, which led to the necessity
      of a well-trained staff for confirmation of microscope results. MATERIALS AND
      METHODS: A new protocol of the optimized scansystem with the addition of a
      fluorescence quencher was evaluated. Pool platelet concentrates contaminated with
      five transfusion-relevant bacterial strains were tested in a blind study.
      RESULTS: In conjunction with new analysis software, the new quenching dye was
      able to reduce significantly unspecific background fluorescence. Sensitivity was
      best for Bacillus cereus and Escherichia coli (3 CFU/ml). DISCUSSION: The
      application of a fluorescence quencher enables automated discrimination of
      positive and negative test results in 60% of all analysed samples.

PMID- 16635070
TI  - Correlation of in vitro platelet quality measurements with in vivo platelet
      viability in human subjects.
AB  - BACKGROUND AND OBJECTIVES: Changes in in vitro platelet quality parameters during
      platelet storage are associated with a decrease of in vivo platelet viability
      after platelet transfusion. Many attempts have been made to identify the most
      predictable in vitro parameters for in vivo performance. We used a riboflavin
      based ultraviolet (UV) light treatment process designed to inactivate pathogens
      and white blood cell (WBC) contaminants in blood products as a model system in
      which to study the correlation of in vitro cell quality with in vivo viability.
      MATERIALS AND METHODS: Platelet products (n = 18) were collected by a standard
      Trima apheresis procedure and treated with one of three dose levels of UV light
      (0, 7.2 or 12.4 J/ml) in the presence of 50 microm riboflavin. Lactate
      production, glucose consumption and P-selectin expression, pH, pCO(2), pO(2),
      hypotonic shock response and swirl were measured during 5 days of platelet
      storage post-UV/RB treatment. Aliquots of these products were radiolabelled on
      day 5 of storage and were subsequently used to determine platelet recovery and
      survival time in autologous subjects. RESULTS: The responses of in vitro cell
      quality were observed to occur in a UV dose-dependent manner. Lactate production
      and pH were identified as the parameters most strongly correlated with platelet
      in vivo recovery, which ranged from 5 to 82%. The correlation coefficients (r)
      for lactate production and pH with in vivo recovery in human subjects were 0.9090
      and 0.8831 with P-values of 0.007 and 0.031, respectively. Lactate production and
      pH were also found to be correlated with platelet survival time, with correlation
      coefficients of 0.8063 and 0.8384 (the P values were 0.01 and 0.001,
      respectively). CONCLUSIONS: Using conditions of riboflavin-based UV light
      treatment, lactate production and pH were identified as having the highest
      correlations with recovery and survival of radiolabelled platelets in healthy
      subjects.

PMID- 16635071
TI  - Prospective open-label study of pharmacokinetics, efficacy and safety of a new
      10% liquid intravenous immunoglobulin in patients with hypo- or
      agammaglobulinemia.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the
      pharmacokinetics, efficacy and safety of a newly developed 10% liquid
      immunoglobulin preparation in patients with primary immunodeficiency diseases.
      This new preparation for intravenous use includes three dedicated virus clearance
      steps in its manufacturing process to ensure a high margin of viral safety.
      MATERIALS AND METHODS: This was a prospective, open-label, non-controlled,
      multicentre study. Twenty-two subjects with primary immunodeficiency were treated
      initially with three infusions of a licensed intravenous immunoglobulin to
      standardize the immunoglobulin G (IgG) replacement therapy of all subjects to the
      same intravenous product. A total of nine infusions of the new 10% liquid
      preparation were subsequently administered. RESULTS: The median terminal half
      life of total IgG following administration of the new preparation was 30.1 days.
      Median terminal half-lives for IgG subclasses IgG(1), IgG(2), IgG(3) and IgG(4)
      were 28.3, 31.3, 20.9 and 24.2 days, respectively. The median total serum IgG
      steady-state trough level was 8.51 g/l. No severe infection episodes started
      after initiation of treatment with the new preparation. The median rate of mild
      or moderate infection episodes was 0.48 per month. A total of 194 infusions with
      the new 10% liquid immunoglobulin preparation were administered. The mean dose
      per infusion was 0.41 g/kg body weight and the maximum infusion rates recorded
      were 8 ml/kg/h. Adverse experiences were mostly mild and unrelated to the study
      drugs. Only 4% of infusions with the new product were followed by one or more
      related adverse experiences. CONCLUSION: The new 10% liquid immunoglobulin
      preparation was well tolerated and shown to have an excellent pharmacokinetic,
      efficacy and safety profile. The liquid formulation provides convenience to
      patients and healthcare professionals.

PMID- 16635072
TI  - Treatment of adult patients with sepsis-induced coagulopathy and purpura
      fulminans using a plasma-derived protein C concentrate (Ceprotin).
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to document the effects of
      supplementation with a plasma-derived protein C concentrate in adult patients
      with infectious purpura fulminans. MATERIALS AND METHODS: We report the effect of
      the administration of a human protein C concentrate (Ceprotin, Baxter, Vienna,
      Austria) in eight adult patients with purpura fulminans. Five patients received
      the concentrate as level-adjusted continuous infusion (10 U/kg/h, target protein
      C activity 100%) and three patients received the concentrate as bolus infusions
      (100 U/kg every 6 h) in addition to standard sepsis therapy. Heparin, fresh
      frozen plasma, antithrombin- and fibrinogen concentrates, low-dose rtPA, and
      platelet transfusions were given when appropriate. RESULTS: Six patients had
      overt disseminated intravascular coagulation: platelets, 19 g/l; fibrinogen, 60
      mg/dl; antithrombin, 47%; prothrombin time, 32%; activated partial thromboplastin
      time (APTT), 88 s; d-dimer, 66 microg/ml; protein C activity, 29% (medians). Five
      patients had septic shock, six renal failure and four respiratory failure.
      Patients received between 5000 and 77,000 U of protein C concentrate over 2.5
      days (median); the protein C activity increased to 184% (median) and coagulopathy
      resolved within 3 days in seven of the eight patients. Six patients survived, one
      died early from fulminant sepsis, and one died after 14 days from candida sepsis.
      CONCLUSIONS: Our data suggest that treatment with a plasma-derived protein C
      zymogen concentrate might be a useful support in adult patients with purpura
      fulminans.

PMID- 16635073
TI  - Eliciting repeat blood donations: tell early career donors why their blood type
      is special and more will give again.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to investigate whether sending
      a personalized and informative letter to early career donors would increase the
      number returning to donate again, as the literature suggests that it is at around
      the third donation that people become career donors. MATERIALS AND METHODS:
      Experimental participants were sent a recruitment letter that included
      information about their own blood type and the percentage of the general
      population with the same blood type who donated. Control participants received a
      recruitment letter with some general information. The aim of the study was to
      determine whether more participants in the experimental group, compared with the
      control group, would donate blood within a 4-week period after receiving their
      personalized recruitment letter. RESULTS: Donors in the experimental group were
      43% more likely to return to donate than those in the control group [chi(2) (1) =
      5.79, P < 0.016]. CONCLUSIONS: Sending out personalized, informative letters
      appears to be a potentially powerful donor-retention tool.

PMID- 16635074
TI  - Economies of scale in blood banking: a study based on data envelopment analysis.
AB  - BACKGROUND AND OBJECTIVES: Exploitation of economies of scale is often argued in
      favour of blood-bank consolidation into large regional centres, despite a lack of
      adequate empirical support. This study was aimed at testing the economies of
      scale hypothesis in a sample of blood centres in the USA. MATERIALS AND METHODS:
      An input-orientated data envelopment analysis (DEA) was used to calculate the
      technical efficiency scores of blood centres, and to determine whether they were
      operating under increasing returns to scale (IRS), constant returns to scale
      (CRS) or decreasing returns to scale (DRS). Correlation between the blood-centre
      efficiency score and the demographic and socioeconomic characteristics of the
      service area was further investigated. RESULTS: Seventy-one blood centres were
      included in the analysis. The scale of operations ranged from 7270 to 275,500 red
      blood cell (RBC) units per year. Six (8%) centres operated under CRS, 29 (55%)
      under IRS, and most of their technical inefficiency was scale-independent, and 26
      (37%) operated under DRS, and most of their technical inefficiency was size
      related. Efficiency scores were unrelated to any demographic or socioeconomic
      characteristics of the blood centre service area. CONCLUSIONS: Within the size
      range of blood centres included in this study, expanding the level of operations
      beyond a certain point leads to DRS.

PMID- 16635075
TI  - The utility of an automated electronic system to monitor and audit transfusion
      practice.
AB  - BACKGROUND AND OBJECTIVES: Transfusion laboratories with transfusion committees
      have a responsibility to monitor transfusion practice and generate improvements
      in clinical decision-making and red cell usage. However, this can be problematic
      and expensive because data cannot be readily extracted from most laboratory
      information systems. To overcome this problem, we developed and introduced a
      system to electronically extract and collate extensive amounts of data from two
      laboratory information systems and to link it with ICD10 clinical codes in a new
      database using standard information technology. MATERIALS AND METHODS: Three data
      files were generated from two laboratory information systems, ULTRA (version 3.2)
      and TM, using standard information technology scripts. These were patient pre-
      and post-transfusion haemoglobin, blood group and antibody screen, and cross
      match and transfusion data. These data together with ICD10 codes for surgical
      cases were imported into an MS ACCESS database and linked by means of a unique
      laboratory number. Queries were then run to extract the relevant information and
      processed in Microsoft Excel for graphical presentation. We assessed the utility
      of this data extraction system to audit transfusion practice in a 600-bed adult
      tertiary hospital over an 18-month period. RESULTS: A total of 52 MB of data were
      extracted from the two laboratory information systems for the 18-month period and
      together with 2.0 MB theatre ICD10 data enabled case-specific transfusion
      information to be generated. The audit evaluated 15,992 blood group and antibody
      screens, 25,344 cross-matched red cell units and 15,455 transfused red cell
      units. Data evaluated included cross-matched to transfusion ratios and pre- and
      post-transfusion haemoglobin levels for a range of clinical diagnoses. Data
      showed significant differences between clinical units and by ICD10 code.
      CONCLUSION: This method to electronically extract large amounts of data and
      linkage with clinical databases has provided a powerful and sustainable tool for
      monitoring transfusion practice. It has been successfully used to identify areas
      requiring education, training and clinical guidance and allows for comparison
      with national haemoglobin-based transfusion guidelines.

PMID- 16635076
TI  - Aetiological factors related to a positive direct antiglobulin test result in
      human immunodeficiency virus-infected patients.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to examine the clinical
      importance and causes of a positive result in the direct antiglobulin test (DAT)
      in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied
      haematological parameters in outpatient samples, and also analysed the impact of
      highly active anti-retroviral therapy (HAART) on the DAT results. STUDY DESIGN
      AND METHODS: Haematological parameters, clinical stages, chemo-antibiotic
      treatments and HAART treatment were studied to determine any relationships with
      DAT results in 115 consecutive HIV(+) patients. RESULTS: Significantly lower
      haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT
      result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim
      suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant
      association with DAT positivity. Patients receiving HAART were less likely to
      have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients
      treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl)
      than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and
      TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The
      surface exploratory analysis indicated the distribution of the positive DATs in
      relationship with the CD4(+) count and Hb levels. CONCLUSIONS: Significantly
      lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection
      and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The
      presence of red blood cell autoantibodies may be associated with anaemia in HIV
      disease in the absence of overt haemolysis.

PMID- 16635077
TI  - Recombinant activated factor VIIa (rFVIIa) in intractable haemorrhage: use of a
      clinical scoring system.

PMID- 16635080
TI  - Developmental signalling pathways in lung cancer.
AB  - Hedgehog, Notch and Wnt signalling are all essential for axial patterning and
      progenitor cell fates in signalling pathways conserved from flies to humans.
      Aberrant activation of these pathways is observed in a wide variety of cancers,
      suggesting that these embryonic signalling pathways contribute in a fundamental
      way to the evolution and maintenance of a malignant phenotype. Because all three
      of these pathways participate in lung development, recent studies have begun to
      explore the connection between lung development, airway epithelial repair and
      lung cancer. Development, repair and malignant transformation of the
      neuroendocrine lineage are all accompanied by aberrant Hedgehog pathway
      activation, whereas Notch and Wnt signalling may be important in other airway
      cell types. Small molecule targeting of these pathways may provide therapeutic
      opportunities in lung cancer. The plant-derived alkaloid cyclopamine is a
      naturally occurring Hedgehog pathway inhibitor that shows therapeutic promise in
      small cell lung cancer, a highly aggressive neuroendocrine tumour. A more
      detailed understanding of how embryonic signalling pathways participate in airway
      epithelial repair and tumourigenesis may reveal more novel therapeutic
      vulnerabilities in lung cancer.

PMID- 16635081
TI  - Small cell lung cancer: treatment review.
AB  - Lung cancer was relatively uncommon at the turn of the 20th century, and has
      increased in prevalence at alarming rates, particularly because of the augmented
      trend in smoking, so that it is now the most common cause of cancer death in the
      world. As almost a quarter of these cancers are of small cell in origin, it seems
      only appropriate that small cell lung cancer receives ample attention, rather
      than seemingly to have been overlooked over the last 10-15 years. Despite its
      generally late presentation and high risk of dissemination, it is exceptionally
      sensitive to chemo-radiotherapy. This review looks at the diverse options of
      treatment that have been used over the last few years and tries to highlight the
      best available. As more than 50% of patients diagnosed with lung cancer are over
      70 years of age and various studies have shown that older people respond just as
      well as their younger counterparts, with similar results in response rates,
      toxicity and outcomes, it is imperative that the older generation are not
      disregarded in terms of age being a contraindication to therapy.

PMID- 16635082
TI  - Diffuse panbronchiolitis in East Asia.
AB  - Diffuse panbronchiolitis is characterized by chronic sinobronchial infection and
      diffuse bilateral centrilobular lesions consisting of peribronchial infiltration
      of inflammatory cells. At present, it is known that diffuse panbronchiolitis is
      relatively restricted to East Asia. This uneven distribution is suspected to be
      highly associated with genetic predisposition located between human leucocyte
      antigen-A and -B loci. Low-dose, long-term macrolide therapy for the disease was
      suggested from a detailed observation of a single case that significantly
      improved by erythromycin therapy. Otherwise simple bactericidal activity of
      macrolides has been assumed as a candidate because of their clinical effect on
      the pathogenesis. In the last 10 years, the possible mechanism underlying the
      effectiveness of macrolide therapy has been dynamically investigated. To
      understand the pathological features and potential targets for macrolides in
      diffuse panbronchiolitis, the authors introduce the incidence of diffuse
      panbronchiolitis in East Asia, the profile of the disease and then trace the
      history of macrolide therapy in this review. The proposed mechanism of action
      includes the inhibition of excessive mucus and water secretion from the airway,
      the inhibition of neutrophil, and sometimes of lymphocyte and macrophage
      accumulating in the airway, the inhibition of transcription factors expressing
      several cytokines and the attenuation of bacterial virulence. Intracellular
      mechanisms of the action of macrolide are a hot topic of interest in research.
      The anti-inflammatory activity of macrolides is independent of their bactericidal
      effect, and a new anti-inflammatory analogue without antimicrobial activity
      should be developed to minimize the emergence of macrolide-resistant
      microorganisms and to maintain the safety of this treatment.

PMID- 16635083
TI  - Extrinsic allergic alveolitis.
AB  - Extrinsic allergic alveolitis (also known as hypersensitivity pneumonitis) is
      caused by repeated inhalation of mainly organic antigens by sensitized subjects.
      This induces a hypersensitivity response in the distal bronchioles and alveoli
      and subjects may present clinically with a variety of symptoms. The aims of this
      review are to describe the current concepts of the immunological response, the
      diverse clinical presentation of this disease, the relevant investigations and
      management, and areas for future studies.

PMID- 16635084
TI  - Expression of peroxiredoxin and thioredoxin in human lung cancer and paired
      normal lung.
AB  - BACKGROUND: Peroxiredoxins (Prxs) have been implicated in regulating many
      cellular processes including cell proliferation, differentiation and apoptosis.
      However, the pathophysiological significance of Prx proteins, especially in lung
      disease, has not been defined. Therefore, the authors investigated the
      distribution and expression of various Prx isoforms in lung cancer and compared
      this with normal lung from human and mouse. METHODS: Patients diagnosed with lung
      cancer who underwent surgery at Ajou Medical Center were enrolled. Expression of
      Prxs, thioredoxin and thioredoxin reductase was analysed by proteomic techniques.
      Immunohistochemistry was performed to localize Prx proteins. RESULTS:
      Immunohistochemical staining showed that the isoforms of Prx I, II, III and V
      were predominantly expressed in bronchial and alveolar epithelium as well as in
      alveolar macrophages of the normal mouse lung. The isoforms I, III and
      thioredoxin were overexpressed in lung cancer tissues compared with normal lungs.
      There was also an increased amount of oxidized form of Prx I and a putative
      truncated form of Prx III in lung cancer samples when analysed on two-dimensional
      electrophoresis. In addition, a 40-kDa intermediate MW protein band and high MW
      bands of over 20 kDa, recognized by anti-Prx (a-Prx) I antibody, were present in
      tissue extracts of lung cancer patients on one-dimensional electrophoresis.
      CONCLUSION: The upregulation of Prx I, Prx III and thioredoxin in lung cancer
      tissue may represent an attempt by tumour cells to adjust to the microenvironment
      in a manner that is advantageous to survival and proliferation.

PMID- 16635085
TI  - Efficacy and safety of high-dose budesonide/formoterol (Symbicort) compared with
      budesonide administered either concomitantly with formoterol or alone in patients
      with persistent symptomatic asthma.
AB  - OBJECTIVE AND BACKGROUND: Budesonide/formoterol 160/4.5 microg, two inhalations
      bd, is an effective and well-tolerated maintenance therapy for patients not
      controlled on inhaled corticosteroids alone. The authors assessed the efficacy
      and safety of a higher dose of budesonide/formoterol in patients with persistent
      symptomatic asthma. METHODS: This was a 24-week, double-blind, double-dummy
      randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36
      microg/day), was compared with corresponding doses of budesonide during weeks 1
      12 and budesonide plus formoterol via separate inhalers during weeks 1-24.
      Efficacy was assessed during weeks 1-12; the primary variable was morning PEF.
      Safety was assessed over weeks 1-24. RESULTS: Patients (n=456; aged 12-79 years)
      had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid
      dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with
      budesonide/formoterol and budesonide plus formoterol, respectively, versus an
      increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide).
      Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus
      budesonide. Budesonide/formoterol and budesonide plus formoterol had similar
      efficacy. All treatments were well tolerated and the incidence of class-related
      adverse events was similarly low in all groups. Changes in serum potassium and
      plasma cortisol were comparable across treatments. CONCLUSIONS: High-dose
      budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well
      tolerated in patients with persistent symptomatic asthma. The findings also
      support the safety of regular high-dose formoterol (36 microg/day).

PMID- 16635086
TI  - Epidermal growth factor receptor targeted therapy with gefitinib in locally
      advanced and metastatic primary lung adenocarcinoma.
AB  - OBJECTIVE: To describe the efficacy of monotherapy with the epidermal growth
      factor receptor-tyrosine kinase inhibitor, gefitinib in patients with locally
      advanced and metastatic primary lung adenocarcinoma. METHODS: A retrospective
      analysis was undertaken of patients who had locally advanced or metastatic lung
      adenocarcinoma treated with gefitinib 250 mg orally once daily until disease
      progression. All patients had either been previously treated with systemic
      cytotoxic chemotherapy and/or radiotherapy or had declined chemotherapy or were
      medically not fit for cytotoxic chemotherapy. RESULTS: A total of 23 patients (13
      men) (15 never smokers) with a median age of 51 years (range 35-79 years)
      received gefitinib monotherapy. Disease control occurred in 14 patients (61%);
      there was a reduction in the size of the primary and/or metastatic tumours
      (partial response (PR)) in 11 patients (48%), and 3 patients (13%) had stable
      disease. The response rate was significantly higher in those who had never smoked
      (10 of 15 (67%)) compared with that of smokers (1 of 8 (13%)) (odds ratio (95%
      confidence interval), 14.0 (1.33-147.43) P=0.027). In total, 11 of 18 patients
      (61%) with a WHO performance status 1 or 2 showed a PR, whereas none with a
      performance status 3 or 4 responded (P=0.037). Response was not affected by the
      patient's age, gender, disease stage, prior chemotherapy treatment, interval
      between diagnosis and commencement of gefitinib or the development of skin
      toxicity. The median time to symptom improvement was 1.5 (range 0.5-6) weeks. The
      median progression-free survival time was: 60 (range 15-138) weeks in patients
      with PR and 34 (range 7-38) weeks in patients with stable disease (P=0.368).
      CONCLUSION: When given alone, gefitinib showed significant antitumour activity in
      patients with locally advanced and metastatic primary lung adenocarcinoma. An
      objective response was observed more frequently in never smokers and exclusively
      in patients with good performance status.

PMID- 16635087
TI  - National survey of spirometer ownership and usage in general practice in
      Australia.
AB  - OBJECTIVES AND BACKGROUND: Despite the lack of data, it is believed that
      spirometry is underutilized in general practice. The aim of the present study was
      to determine the availability of spirometry and the level of spirometry training
      in general practice throughout Australia and compare with international data.
      METHODS: In total, 5976 general practices throughout Australia were sent a
      questionnaire requesting details of spirometer ownership, usage and the level and
      source of spirometry training. To exclude response bias, a follow-up telephone
      survey was conducted of 160 practices that did not respond to the initial survey.
      RESULTS: Of practices 19.5% (1125) responded to the initial survey with 64.2%
      (722) of these owning a spirometer and 83.9% in the follow-up sample. Common
      reasons for not owning a spirometer were equipment cost (53.3%) and insufficient
      remuneration (32.8%). Most practices (67.0%) performed one or more tests per
      week. Practices commonly used spirometry to diagnose (89.5%) and manage (93.9%)
      asthma, assess breathlessness (83.4%) and to detect and manage other diseases
      such as COPD (77.7%). Spirometer accuracy was never checked using a syringe 77.8%
      of practices and 40% did not test a healthy subject as part of their quality
      assurance programme. Spirometry training was received most commonly through
      courses run by general practice organizations (38.2%), and the duration of
      training courses was <2 h in 40% of cases. CONCLUSION: Despite high spirometer
      ownership in general practice, the frequency of use is low. Low rates of
      verification of spirometer accuracy and performance suggest the need for
      reliable, stable spirometers to be available to general practitioners. Regular
      and more comprehensive training in spirometry is needed.

PMID- 16635088
TI  - Prevalence and characteristics of pleural effusions in superior vena cava
      syndrome.
AB  - OBJECTIVE AND BACKGROUND: The prevalence and characteristics of pleural effusions
      occurring in adults with the superior vena cava (SVC) syndrome are unknown. The
      purpose of the present study was to characterize these pleural effusions.
      METHODS: Charts of patients diagnosed with SVC syndrome at a tertiary care
      referral centre were reviewed. Radiographs were evaluated for the presence and
      size of pleural effusions, presence and location of masses and mediastinal width.
      If a pleural effusion was present, the patient's chart and a pre-existing
      database on pleural effusions were searched to determine whether the effusion was
      sampled and the results of any laboratory investigations on the fluid. RESULTS:
      The SVC syndrome occurred in 78 patients. Malignancy was the aetiology in 60% of
      the cases and bronchogenic carcinoma was the most common malignancy. An
      intravascular device was the aetiology in the majority of benign cases. Pleural
      effusion was found in 70% of patients with a malignant aetiology and 58% of those
      with a benign cause (P=0.345). The mean size of the effusions was larger in
      malignant cases (P=0.012). Of the 44 effusions 22 were sampled (17 in malignancy
      and five with benign processes); none was transudates, 20 (91%) were exudative
      (four of these were chylous) and the remaining two were reported as exudates but
      did not have pleural chemistries documented. CONCLUSIONS: More than half of
      patients with SVC syndrome have pleural effusions, regardless of the aetiology.
      However, the effusions are larger when associated with malignancy. The majority
      of these effusions are exudative and occasionally chylous. None was transudates.

PMID- 16635089
TI  - Stability of the EasyOne ultrasonic spirometer for use in general practice.
AB  - OBJECTIVE AND BACKGROUND: Spirometry is recommended for the diagnosis and
      management of chronic respiratory diseases in the community. Spirometer accuracy
      is critical, but few general practitioners meet the American Thoracic Society and
      European Respiratory Society (ATS/ERS) recommendation for daily calibration. The
      aim of this study was to assess the accuracy and stability of a portable
      ultrasonic spirometer (EasyOne) that the manufacturer claims does not require
      regular calibration. METHODS: Six EasyOne spirometers were used in a practice
      based spirometry study. Inspiratory and expiratory accuracy was checked
      periodically using a certified 3-L syringe. Paired calibration checks were
      performed using a dedicated mouthpiece assembly (spirette) and randomly selected
      spirettes. RESULTS: The six spirometers were used for up to 26 weeks (mean 23.9
      weeks) and a total of 1041 spirometry tests and 75 syringe calibrations were
      performed. All inspiratory and expiratory calibration checks using a dedicated or
      randomly selected spirette met the ATS/ERS accuracy criterion (3.00+/-0.105 L).
      The mean (range) expiratory volume deviation from target volume (3.00 L) was
      0.011 L (-0.06-0.09 L) using a dedicated spirette and 0.046 L (-0.09-0.10 L)
      using randomly selected spirettes. The deviation from target was not affected by
      the mean flow generated during the calibration procedure. There was no change in
      calibration during the study. CONCLUSIONS: This study supports the manufacturer's
      claim that the EasyOne spirometer maintains its calibration during routine
      clinical use in general practice and does not require daily calibration as
      specified in international spirometry guidelines.

PMID- 16635090
TI  - Evaluation of patients followed up in a cigarette cessation clinic.
AB  - OBJECTIVES: The aim of this study was to evaluate the demographic characteristics
      and factors determining success in a smoking cessation clinic in smokers who
      completed a 1-year follow up. METHOD: A total of 349 patients were assessed
      retrospectively. RESULTS: There were 238 men (mean age: 41+/-13.5 years) and 111
      women (mean age: 37+/-11.9 years) (t-test P=0.004). The average age at which they
      began to smoke, number of years of smoking and the number of cigarettes/day were
      17.5+/-5.2 years (median 17), 22.1+/-13.3 years, 23.5+/-12.0, respectively.
      Cigarette smoking was mostly observed in university graduates (56.8%) and a
      moderate negative correlation existed between education status and smoking
      duration (r=-0.27, P=0.000). Patients with a Fagerstrom Tolerance Questionnaire
      score of >or=6 and those exposed to cigarette smoke in childhood tended to
      commence and become committed smokers later in life (chi2=4.915, P=0.027). In
      all, 151 patients (43.26%) were successful in quitting (chi2=36.4, P=0.000). Of
      these, 87 (24.93%) used medication such as nicotine patches (13.5%), bupropion
      (7.2%), nicotine patches+bupropion (4.3%) and 64 (18.33%) refused medication, but
      came for professional support. CONCLUSION: Increased education level, behavioural
      therapy and intensive motivational support, follow-up visits and phone calls all
      appear to play important roles in smoking cessation. Families also play a major
      role.

PMID- 16635091
TI  - Four cases of pulmonary Mycobacterium avium intracellulare complex presenting as
      a solitary pulmonary nodule and a review of other cases in Japan.
AB  - OBJECTIVE: To evaluate clinical findings of patients with a solitary pulmonary
      nodule in Japan caused by pulmonary Mycobacterium avium complex (MAC) disease.
      METHODS: The authors investigated the clinical features of 12 patients diagnosed
      as having pulmonary MAC disease who had presented with a solitary pulmonary
      nodule. RESULTS: The causative microorganisms were M. avium in seven patients,
      Mycobacterium intracellulare in two and MAC in three. The diagnostic methods were
      bronchoscopic biopsy or percutaneous lung biopsy in three patients and surgical
      operations in the remaining nine. Eleven patients had a complete surgical
      resection of the nodule and antituberculous drugs were administered to eight. On
      X-ray, there was an absence of calcification, satellite lesions, cavities, or
      bronchoectasis that are often thought to be characteristic of pulmonary
      mycobacterial disease. Differentiation from lung cancer was thought necessary in
      five patients. There was no microbiological or radiological relapse in those who
      underwent complete surgical resection. CONCLUSIONS: Because treatment is often
      poorly effective for patients with pulmonary non-tuberculous mycobacterial
      disease, it is important to identify the causative microorganisms by performing a
      culture examination of resected lung tissue especially if there is a solitary
      pulmonary nodule.

PMID- 16635092
TI  - Clinical predictors for the detection of community-acquired pneumonia in adults
      as a guide to ordering chest radiographs.
AB  - OBJECTIVE: To identify sensitive clinical predictors for the detection of
      community-acquired pneumonia in adults as a guide to when to order a CXR.
      METHODS: In total, 79 outpatients presenting with at least one of the following
      clinical features of pneumonia: fever, cough, sputum, chest pain, dyspnoea and
      coarse crackles and who underwent CXR to detect pneumonia were examined
      retrospectively. The relationship between these clinical features and the
      presence of pneumonia on CXR was determined. RESULTS: A total of 24 patients
      (30.4%) had radiological evidence of pneumonia. In total, 22 presented with four
      clinical signs: fever, cough, sputum and coarse crackles. The sensitivity and the
      specificity of detecting pneumonia based on these four clinical signs mentioned
      was 91.7% and 92.7%, respectively. CONCLUSIONS: As a diagnostic strategy, the
      ordering of CXR to confirm a diagnosis of community-acquired pneumonia in adults
      is recommended when patients have the following four clinical signs: fever,
      cough, sputum and coarse crackles.

PMID- 16635093
TI  - Fractional exhaled nitric oxide concentration is increased in asbestosis and
      pleural plaques.
AB  - OBJECTIVE AND BACKGROUND: Asbestos exposure induces generation of reactive oxygen
      and nitrogen species. Nitric oxide is involved in asbestos-related lung toxicity
      in vitro and can be measured non-invasively in humans in exhaled breath. The
      authors hypothesized that fractional exhaled nitric oxide concentration (FENO)
      would be increased in subjects with asbestos-related lung disorders. METHODS:
      FENO was measured in 56 subjects with asbestos-related disorders (asbestosis: 12;
      pleural plaques: 32; asbestos-related diffuse pleural thickening: 12) and in 35
      normal subjects. The authors also measured exhaled carbon monoxide, another
      marker of lung inflammation. RESULTS: Median (25-75 percentile) FENO was
      increased in subjects with asbestosis (7.9 (6.6-15.7) p.p.b.; P=0.001) and
      pleural plaques (6.3 (5.3-9) p.p.b.; P=0.03) compared with normal controls (4.6
      (3.5-6) p.p.b.). Subjects with DPT had a median FENO of 5.6 p.p.b., similar to
      controls. No significant differences in exhaled carbon monoxide were observed
      between controls (1.0+/-0.3 p.p.m.) and subjects with asbestosis (1.3+/-0.3
      p.p.m.), pleural plaques (1.2+/-0.3 p.p.m.) or diffuse pleural thickening (1.1+/
      0.3 p.p.m.). CONCLUSIONS: FENO is raised in asbestosis consistent with lung
      inflammation, and also in pleural plaques.

PMID- 16635094
TI  - Elevated serum surfactant protein A and D in pulmonary alveolar microlithiasis.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by
      widespread localization of calcispherites in the alveolar spaces. The authors
      report two cases of PAM, with markedly elevated sera concentrations of surfactant
      protein-A and surfactant protein-D, which showed a tendency to increase as the
      disease progressed. Therefore, surfactant protein-A and surfactant protein-D may
      function as serum markers to monitor the disease activity and progression of PAM.

PMID- 16635095
TI  - Multifocal mesenchymal hamartoma of the chest wall.
AB  - Chest wall hamartomas are extremely rare. Frequently mesenchymal hamartomas are
      presented as a single mass and contain some primitive mesenchymal elements such
      as chondroid and trabecular bone structures. A 60-year-old man presented to
      hospital with chest pain. Thirteen years earlier, his CXR and thoracic CT showed
      three masses on the right and two masses on the left, but he had not received any
      treatment thereafter. His CT showed the same masses present 13 years earlier, but
      they were bigger and right thoracotomy was undertaken. At thoracotomy, two
      sections of the mass in the right posterior mediastinum and one section of the
      mass in the right apex were excised. They had an occasional bloody appearance and
      contained small cystic areas, and some areas were extremely hard. Microscopic
      examination showed that the lesions consisted of mature adipose tissue, a large
      number of veins of different diameters and collagen tissue. Besides, primitive
      mesenchymal elements, lymphoid cell accumulations and trabecular bone structures
      were seen focally. Bilateral chest wall hamartomas are extremely rare and may be
      confused with malignancy.

PMID- 16635096
TI  - Pulmonary blastoma within bronchioloalveolar cell carcinoma.
AB  - Pulmonary blastoma is a rare tumour of the lung composed of epithelial and
      mesenchymal elements that morphologically resemble the embryonal structure of the
      lung. The authors report a 79-year-old man who was diagnosed with a pulmonary
      blastoma within bronchioloalveolar cell carcinoma. Macroscopic, histopathological
      and immunohistochemical findings suggested that the pulmonary blastoma was
      closely associated with the bronchioloalveolar cell carcinoma.

PMID- 16635097
TI  - Human pulmonary dirofilariasis: a case report and review of the recent Japanese
      literature.
AB  - Human pulmonary dirofilariasis is a rare zoonotic infection caused by the dog
      heartworm Dirofilaria immitis, which is transmitted via a vector/intermediate
      host, generally the mosquito. The authors present a case of histologically
      diagnosed human pulmonary dirofilariasis, in which the lesion was resected using
      video-assisted thoracic surgery (VATS). The authors also review 24 cases of such
      zoonosis reported in Japan from 1998 to 2004. Of these 24 patients with human
      pulmonary dirofilariasis, 12 (50%) were men (mean age 54 years, range 29-80
      years) and 67% were asymptomatic. Most patients (83%) had a solitary lung nodule,
      95% of the lesions were <30 mm and 13% had a pleural effusion. VATS was performed
      to obtain a histopathological diagnosis in the majority (61%) of patients whom
      the authors reviewed. VATS would appear to be the best method for diagnosing
      pulmonary dirofilariasis.

PMID- 16635098
TI  - Histopathological diagnosis of endobronchial endometriosis treated with argon
      laser.
AB  - The authors present a case of endobronchial endometriosis with catamenial
      haemoptysis. The lesion was diagnosed as endobronchial endometriosis based on
      histopathological examination of a bronchial biopsy from the right second carina.
      Fibreoptic bronchoscopic examination revealed a tiny hyperaemic submucosal area
      with bleeding and a brown-coloured diverticulum at bottom of this lesion
      encompassing a 2-cm2 area at the right second carina. Multiplanar reconstructions
      of a spiral CT scan revealed a 0.5-cm lesion that looked like a diverticulum at
      the right second carina. The patient was treated with argon laser at
      bronchoscopy. Following treatment, the patient has been asymptomatic with no
      recurrence of haemoptysis.

PMID- 16635099
TI  - Alternative methods for developmental toxicity testing.
AB  - Alternatives to animal testing in developmental toxicology have been the subject
      of three decades of research. The aims of these investigations have been to
      reduce animal experimentation, to refine effect assessment and mechanistic
      studies, and to accelerate and simplify safety testing in an area of toxicology
      that uses relatively many animals. Many alternatives have been developed over the
      years with different compexities, using biologic material ranging from continuous
      cell lines to complete embryos. The validation of alternatives and their
      application in testing strategies is still in its infancy, although significant
      steps towards these aims are currently being made. The introduction of the
      genomics technology is a promising emerging area in developmental toxicity
      testing in vitro. Future application of alternatives in testing strategies for
      developmental toxicity may significantly gain from the inclusion of gene
      expression studies, given the unique programme of gene expression changes in
      embryonic and foetal development.

PMID- 16635100
TI  - Proteomics: recent applications and new technologies.
AB  - Interest in proteomics as a tool for drug development and a myriad of other
      applications continues to expand at a rapid rate. Proteomic analyses have
      recently been conducted on tissues, biofluids, subcellular components and
      enzymatic pathways as well as various disease and toxicological states, in both
      animal models and man. In addition, several recent studies have attempted to
      integrate proteomics data with genomics and/or metabonomics data in a systems
      biology approach. The translation of proteomic technology and bioinformatics
      tools to clinical samples, such as in the areas of disease and toxicity
      biomarkers, represents one of the major opportunities and challenges facing this
      field. An ongoing challenge in proteomics continues to be the analysis of the
      serum proteome due to the vast number and complexity of proteins estimated to be
      present in this biofluid. Aside from the removal of the most abundant proteins, a
      number of interesting approaches have recently been suggested that may help
      reduce the overall complexity of serum analysis. In keeping with the increasing
      interest in applications of proteomics, the tools available for proteomic
      analyses continue to improve and expand. For example, enhanced tools (such as
      software and labeling procedures) continue to be developed for the analysis of 2D
      gels and protein quantification. In addition, activity-based probes are now being
      used to tag, enrich and isolate distinct sets of proteins based on enzymatic
      activity. One of the most active areas of development involves microarrays.
      Antibody-based microarrays have recently been released as commercial products
      while numerous additional capture agents (e.g. aptamers) and many additional
      types of microarrays are being explored.

PMID- 16635101
TI  - Preclinical assessment of gastrooesophageal tolerance of the new antiosteoporotic
      drug strontium ranelate: an endoscopic study in monkeys.
AB  - This study was aimed at evaluating the digestive tolerance of the new
      antiosteoporotic drug, strontium ranelate, and to compare it to that of another
      strontium salt, strontium chloride (SrCl2). Strontium ranelate, SrCl2, or placebo
      were administered orally (capsules) to 3 groups of 2 male and 2 female cynomolgus
      monkeys (Macaca fascicularis) once a day for 7 days at a dose of 2 g/day, which
      is the recommended therapeutic dose in man. Endoscopic examination of the
      oesophagus, the stomach and the first part of the duodenum was performed on
      fasted animals approximately 3 hr after the first (Day 1) and last dosing (Day
      7), and, on Day 8 and Day 14 in case of lesions on Day 7. Strontium ranelate did
      not induce any acute or subchronic toxic effect on the gastric mucosa, the
      oesophagus and the first part of the duodenum. On the contrary, acute and
      superficial damages were noted on all animals receiving SrCl2 such as
      haemorrhagic and erosive lesions (formation of an ulcer in one male and a marked
      congestive antritis in one female). These effects were reversible after cessation
      of treatment. The microscopic examination of biopsies sampled at the site of
      gastric lesions revealed moderate granulocyte infiltration, indicating a local
      irritating origin of the lesions. Strontium ranelate by oral route is safe for
      the gastric mucosa while SrCl2 induced superficial and reversible lesions.

PMID- 16635102
TI  - The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins
      phosphorylation in dichlorvos-induced delayed neurotoxicity in rats.
AB  - The present investigation was carried out to assess the protective efficacy of
      nimodipine against dichlorvos-induced organophosphate induced delayed
      neurotoxicity (OPIDN). Single subcutaneous dose of dichlorvos (200 mg/kg body
      weight) led to a consistent increase in the activity of both microtubule
      associated protein kinases viz. Ca2+/Calmodulin-dependent and cAMP dependent
      protein kinases, at all post exposure intervals (day 7, 15 and 21) as compared to
      that of controls. Autoradiography followed by microdensitometric studies
      demonstrated enhanced phosphorylation of 55 kDa and 280 kDa proteins in
      dichlorvos-exposed animals. These two proteins were confirmed to be tubulin and
      microtubule associated protein-2 (MAP-2) by western blotting. The
      hyperphosphorylation of these two proteins was shown to interfere with the
      assembly of neuronal microtubules as shown by electron microscopic studies that
      may eventually lead to possible disruption of neuronal cytoarchtecture resulting
      in axonal degeneration. Administration of nimodipine along with dichlorvos
      brought about a significant reduction in the activities of both the kinases as
      well as the extent of microtubule associated protein phosphorylation. This
      indicates that nimodipine, a centrally acting calcium channel blocker, may
      contribute to the amelioration of dichlorvos induced neurotoxicity by attenuation
      of calcium mediated disruption of cytoskeletal proteins and hence, calcium
      channel blockers like nimodipine have great future as new therapeutic agents for
      OPIDN.

PMID- 16635103
TI  - Influence of naringenin on oxytetracycline mediated oxidative damage in rat
      liver.
AB  - Naringenin is a naturally occurring citrus flavanone, which has been reported to
      have a wide range of pharmacological properties. The present work was carried out
      to evaluate the effect of naringenin on antioxidant and lipid peroxidation status
      in liver of oxytetracycline-intoxicated rats. Intraperitonial administration of
      oxytetracycline 200 mg/kg for 15 days resulted a significant elevation in serum
      hepatospecific markers such as aspartate transaminase, alanine transaminase,
      alkaline phosphatase, lactate dehydrogenase, and bilirubin and the levels of
      lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS) and
      lipid hydroperoxides) in liver. Oxytetracycline also caused a significant
      reduction in the activities of superoxide dismutase, catalase, glutathione
      peroxidase, reduced glutathione (GSH), vitamin C and vitamin E in liver. Oral
      administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly
      decreased the activities of serum aspartate transaminase, alanine transaminase,
      alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along
      with significant decrease in the levels of lipid peroxidation markers in the
      liver. In addition, naringenin significantly increased the activities of
      superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,
      vitamin C and vitamin E in liver of the oxytetracycline-treated rats. Our results
      demonstrate that naringenin exhibited antioxidant property and decrease the lipid
      peroxidation against oxytetracycline-induced oxidative stress in liver.

PMID- 16635104
TI  - Acute myocardial infarction associated with amitriptyline overdose.
AB  - Tricyclic antidepressant overdose is known to cause cardiopulmonary and central
      nervous system complications. As with other cardiovascular complications,
      amitriptyline toxicity may cause acute myocardial infarction. This paper reports
      the case of a young female with acute myocardial infarction as a novel
      consequence of tricyclic antidepressant overdose.

PMID- 16635105
TI  - Attenuation of abnormalities in the lipid metabolism during experimental
      myocardial infarction induced by isoproterenol in rats: beneficial effect of
      ferulic acid and ascorbic acid.
AB  - The present study aims at evaluating the effect of the combination of ferulic
      acid and ascorbic acid on isoproterenol-induced abnormalities in lipid
      metabolism. The rats were divided into eight groups: Control, isoproterenol,
      ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic
      acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic
      acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg
      b.w.t.) both alone and in combination was administered orally for 6 days and on
      the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected
      intraperitoneally to induce myocardial injury to rats. Induction of rats with
      isoproterenol resulted in a significant increase in the levels of triglycerides,
      total cholesterol, free fatty acids, free and ester cholesterol in both serum and
      cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low
      density lipoprotein and very low density lipoprotein-cholesterol was also
      observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in
      the level of high density lipoprotein in serum and in the phospholipid levels, in
      the heart of isoproterenol-intoxicated rats was observed, which was paralleled by
      abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol
      ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase.
      Pre-cotreatment with the combination of ferulic acid and ascorbic acid
      significantly attenuated these alterations and restored the levels to near normal
      when compared to individual treatment groups. Histopathological observations were
      also in correlation with the biochemical parameters. These findings indicate the
      synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol
      induced abnormalities in lipid metabolism.

PMID- 16635106
TI  - Aflatoxin B1-induced DNA damage in Labeo rohita: protective effect of an
      antioxidant supplement, Amrita Bindu.
AB  - The present study was undertaken to investigate the effect of potent
      hepatocarcinogen aflatoxin B1 in adduct formation and DNA damage in Labeo rohita.
      Also, the salubrious efficacy of an antioxidant supplement Amrita Bindu (based on
      Indian system of Medicine) was investigated. Fish weighing 175-250 g were
      administered intraperitoneally a single dose of 100 microg aflatoxin B1/100 g
      body wt. and another group was given 20% solution of Amrita Bindu along with
      aflatoxin B1 at 100 microg/100 g body wt. On the 3rd and 6th day, the liver
      tissue was analyzed for aflatoxin concentration, aflatoxin-DNA adduct formation
      and DNA damage measured in terms of single strand breaks. The fishes administered
      with aflatoxin B1 showed elevated concentration of aflatoxin along with a
      parallel increase in the DNA adduct when compared with the controls. While the
      fish co-administered with Amrita Bindu showed 34% and 24% reduction in aflatoxin
      deposition (accumulation) and aflatoxin-DNA adduct formation respectively on the
      3rd day, a further reduction by around 41% and 33% in aflatoxin deposition and
      DNA adduct formation respectively was observed on the 6th day. Furthermore, the
      increased single strand breaks (measured by alkaline single cell gel assay) and
      fragmentation observed in agarose gel electrophoresis in aflatoxin B1
      administered fish were significantly reduced by Amrita Bindu co-administration.
      In conclusion, this is the first report to show aflatoxin B1-induced DNA adduct
      formation and DNA damage in one of the major Indian culturable fish, Labeo
      rohita. Also, our observations show that the antioxidant supplement, Amrita
      Bindu, has a potential role in ameliorating the aflatoxin B1-induced DNA damage
      thus suggesting its applicability in preventing the vital macromolecule DNA.

PMID- 16635107
TI  - Regulation of gender-dependent CYP2A expression in pigs: involvement of androgens
      and CAR.
AB  - The expression of drug metabolizing cytochrome P4502A (CYP2A) is highly gender
      dependent in minipigs with the highest activity in females. In other species,
      orthologs of CYP2A have been shown to be under the regulation of nuclear receptor
      constitutive androstane receptor, whereas little is known about regulation in
      pigs. To investigate the effect of sex hormones on porcine cytochrome P450 CYP2A
      and CYP3A expression was assessed in liver samples taken before and after
      castration of sexually mature minipig boars. Removal of the primary androgen
      source resulted in significant increases of CYP2A mRNA, protein and enzyme
      activity levels. Likewise, expression of CYP3A was increased, although to a
      lesser extent. To examine the involvement of constitutive androstane receptor in
      the regulation of CYP2A, primary porcine hepatocytes were exposed to modulators
      of murine constitutive androstane receptor and human constitutive androstane
      receptor activity. The CYP2A activity was significantly increased by exposure to
      phenobarbital, an indirect activator of constitutive androstane receptor, and the
      human constitutive androstane receptor-ligand CITCO. In contrast, no effect was
      seen following exposure to the potent murine constitutive androstane receptor
      ligand TCPOBOP and the hormonal murine constitutive androstane receptor-ligands
      androstenol and oestrone. Thus, the results support that 1) porcine CYP2A is
      reversibly inhibited by androgens on a transcriptional basis in vivo; 2) the
      induction profile of CYP2A in vitro shares similarity with that of human
      constitutive androstane receptor-regulated CYPs, indicating an involvement of a
      porcine constitutive androstane receptor in the regulation of CYP2A.

PMID- 16635108
TI  - Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist,
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of
      the guinea-pig.
AB  - Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the
      gastrointestinal tract. The present study examined the motor effects of exogenous
      ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and
      the influence of drugs on the ATP-induced responses. High micromolar
      concentrations of ATP caused two types of contraction, a phasic, cholinergic
      response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction
      was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin
      tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response
      was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or
      pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction
      were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate
      6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M,
      respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M)
      caused guanethidine-resistant relaxation. This response was not influenced by
      tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by
      apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5)
      M), in a surmountable manner. A high degree of tachyphylaxis was observed with
      the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M)
      of PPADS failed to influence ileum contractions to exogenous acetylcholine or
      histamine. It is concluded that, in addition to its direct contractile action in
      the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic
      neurones, an effect whose mechanism is largely different from that of alpha,beta
      methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor
      mediated effect on the smooth muscle. All motor effects of ATP are inhibited by
      the antagonist PPADS.

PMID- 16635109
TI  - Evaluation of urinary 8-hydroxydeoxyguanine in healthy Japanese people.
AB  - The urinary concentration of 8-hydroxydeoxyguanine (8-OHdG), which is a biomarker
      of oxidative DNA damage, was measured in 248 healthy Japanese, and its
      correlations with life style, urinary metal elements, serum antioxidants, and
      other plasma or serum factors were investigated. The mean urinary concentration
      of 8-OHdG was 15.2+/-5.71 ng/mg creatinine. Mean urinary 8-OHdG was not
      significantly different in terms of age (<45, >or=45), gender, smoking (no, <20,
      >or=20), and alcohol consumption (no, occasionally, sometimes and usually).
      Moreover, multiple regression analysis showed a significant association between
      urinary 8-OHdG and urinary arsenic (As) or chromium (Cr), and a tendency for
      association between the former and aluminum (Al) and nickel (Ni). Age, gender and
      plasma or serum factors including antioxidants, lipid peroxide, HbA1c, BUN, and
      iron did not show such an association. The present study suggests that natural
      exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative
      DNA damage in healthy people under usual environmental management. Therefore, the
      measurement of urinary metals such as As, Ni and Cr is prerequisite for the study
      of the relationship between urinary 8-OHdG and other variable factors.

PMID- 16635110
TI  - Reduced blood platelet sensitivity to aspirin in coronary artery disease: are
      dyslipidaemia and inflammatory states possible factors predisposing to sub
      optimal platelet response to aspirin?
AB  - The study was designed to assess blood platelet sensitivity to acetylsalicylic
      acid and its associations with dyslipidaemia and inflammation in coronary artery
      disease patients. Platelet non-responsiveness to aspirin is associated with an
      increased risk of serious cardiovascular events. Several environmental and
      hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid
      response. Forty-five coronary artery disease patients and 45 non-coronary artery
      disease controls received acetylsalicylic acid at a daily dose of 75-150 mg.
      Controls were examined twice: on the day of entering the study and 10 days later.
      Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet
      thromboxane generation. Aggregation was studied in platelet-rich plasma using
      turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy
      percent of coronary artery disease patients showed an extent of collagen-induced
      aggregation above the upper quartile of the reference range compared with 8-15%
      in controls (P<0.003). For arachidonic acid-activated aggregation these
      proportions were 45-50% in coronary artery disease versus 7% in controls
      (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated
      platelet inhibition positively correlated with increased triglycerides (in
      arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol
      (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated
      serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease
      patients urine 11-dehydrothromboxane B2 concentrations were significantly
      increased compared to controls after 10 day acetylsalicylic acid intake (563; 313
      728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence
      of suboptimal acetylsalicylic acid response incidence was more common in patients
      with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet
      reactivity and thromboxane generation was less effective in these patients.
      Dyslipidaemia and chronic inflammatory states may promote suboptimal
      acetylsalicylic acid response in coronary artery disease patients.

PMID- 16635111
TI  - Cocaine-induced inhibition of ATP-sensitive K+ channels in rat ventricular
      myocytes and in heart-derived H9c2 cells.
AB  - Cocaine use may cause coronary artery spasm and acute myocardial
      ischaemia/infarction. However, its effects on ATP-sensitive K+ (KATP) channel, an
      ion channel responsible for ischaemic preconditioning, remain unknown. In
      isolated rat ventricular myocytes with whole-cell experiments, cocaine can
      reverse action potential shortening and increased K+ current caused by the
      openers of ATP-sensitive K+ (KATP) channels. In inside-out patches, cocaine
      applied to intracellular surface suppressed KATP-channel activity in a
      concentration-dependent manner with an IC50 value of 9.2 microM; however, it did
      not modify the single-channel conductance of this channel. The change in the
      kinetic behaviour of KATP channels caused by cocaine is primarily the result of
      an increase in mean closed time and a decrease in mean open time. Cocaine-induced
      inhibition of KATP channels is independent of change in intracellular ATP
      concentrations. In heart-derived H9c2 cells, cocaine is also capable of
      suppressing KATP-channel activity. The present study provides evidence that
      cocaine can produce a depressant action on KATP channels in cardiac myocytes, and
      thus disturb ischaemic preconditioning in clinical settings.

PMID- 16635112
TI  - Effects of the local anaesthetic ropivacaine on vascular reactivity in the mouse
      perfused mesenteric arteries.
AB  - Previous clinical and experimental studies have indicated that ropivacaine, a
      local anaesthetic agent, exerts vasoconstrictor effects. In this study, the
      contractile effects of ropivacaine were investigated in vitro on mesenteric
      arteriolar beds obtained from 22 adult male C57BL/6J mice. The mesenteric
      arteriolar bed was perfused at constant rate (2 ml/min.) with oxygenated
      physiological salt solution using a roller pump. First we studied the effects of
      ropivacaine (3.2x10(-4) to 2.2x10(-2) mol/l) on the perfusion pressure and
      observed a dose-dependent pressor response, reaching a maximal increase of 26.0+/
      3.7 mmHg. In a second study, we observed that after the mechanical removal of the
      endothelium ropivacaine-induced contractile responses were significantly reduced
      to a maximal of 13.5+/-0.7 mmHg. In a third set of experiments, we observed that
      under the effect of the cyclooxygenase inhibitor indomethacin (0.01 micromol/l)
      the ropivacaine-induced pressor response was significantly reduced to a maximal
      increase of 17.5+/-0.4 mmHg. This is the first evidence that this long-acting
      local anesthetic causes vasoconstriction in the perfused mesenteric arteriolar
      bed and that, at least in part, this effect is mediated by the endothelium since
      the cyclooxygenase inhibitor indomethacin reduced the ropivacaine-induced
      vasoconstriction to approximately 50%.

PMID- 16635113
TI  - Facilitation action of N-acetylcysteine on the anticonvulsant effect of sodium
      valproate in mice.

PMID- 16635114
TI  - Clinical competencies achievement profiles - a way forward for students with
      disabilities?

PMID- 16635115
TI  - Of pendulums and sheriffs.

PMID- 16635116
TI  - Getting the measure of interprofessional learning.

PMID- 16635117
TI  - How education can disable discrimination.

PMID- 16635118
TI  - Thinking outside the (tick) box: rescuing professionalism and professional
      judgement.

PMID- 16635119
TI  - Making sense of qualitative data analysis: an introduction with illustrations
      from DIPEx (personal experiences of health and illness).
AB  - OBJECTIVES: This paper outlines an approach to analysing qualitative textual data
      from interviews and discusses how to ensure analytic procedures are appropriately
      rigorous. OVERVIEW: Qualitative data analysis should begin at an early stage in
      data collection and be highly systematic. It is important to identify issues that
      emerge during the data collection and analysis as well as those that the
      researcher may have anticipated (from reading or experience). Analysis is very
      time-consuming, but careful sampling, the collection of rich material and
      analytic depth mean that a relatively small number of cases can generate insights
      that apply well beyond the confines of the study. One particular approach to
      thematic analysis is introduced with examples from the DIPEx (personal
      experiences of health and illness) project, which collects video- and audio-taped
      interviews that are freely accessible through http://www.dipex.org. EVALUATION:
      Qualitative analysis of patients' perspectives of illness can illuminate numerous
      issues that are important for medical education, some of which are unlikely to
      arise in the clinical encounter. Qualitative studies can also cover a much
      broader range of experiences - of both common and rare disease - than clinicians
      will see in practice. The DIPEx website is based on qualitative analysis of
      collections of interviews, illustrated with hundreds of video and audio clips,
      and is an innovative resource for medical education.

PMID- 16635120
TI  - Validating the Readiness for Interprofessional Learning Scale (RIPLS) in the
      postgraduate context: are health care professionals ready for IPL?
AB  - AIMS: This paper describes the process of validating the Readiness for
      Interprofessional Learning Scale (RIPLS) for use with postgraduate health care
      professionals. CONTEXT: The RIPLS questionnaire has proved useful in the
      undergraduate context, enabling tutors to assess the readiness of students to
      engage in interprofessional learning (IPL). With the drive in the National Health
      Service (NHS) to deliver health care in interprofessional teams, it seems logical
      to ask whether postgraduate education should, or could, be delivered successfully
      in interprofessional contexts. As a preliminary to undertaking an extended IPL
      project, the researchers tested the validity of the RIPLS tool in the
      postgraduate health care context. METHOD: A modified version of the RIPLS
      questionnaire was administered to all general practitioners, nurses, pharmacists
      and allied health professionals in the Dundee Local Health Care Cooperative
      (LHCC) (n = 799). A total of 546 staff responded (68%). RESULTS: Three factors,
      comprising 23 statements, emerged from the statistical analysis of the survey
      data, namely, teamwork and collaboration, sense of professional identity and
      patient-centredness. The internal consistency measure was 0.76. Analysis of
      variance suggested some key differences between the different professions in
      respect of the factors. CONCLUSIONS: The RIPLS questionnaire was validated for
      use in the postgraduate context, thus providing researchers with a tool for
      assessing health professionals' attitudes towards interprofessional learning at
      practice level, community health partnership level or at a national level of
      education and training. Significant differences between professional groups
      should be taken into account in designing any interprofessional learning
      programme.

PMID- 16635121
TI  - Surgeons' participation in continuing medical education: is it evidence-based?
AB  - BACKGROUND: Interactive forms of continuing medical education (CME) are more
      likely to improve clinical practice than traditional, passive approaches. This
      study investigated CME participation and preferences among surgeons. METHOD:
      Questionnaire survey of surgeons in New South Wales, Australia. RESULTS: On
      average, respondents (n = 418, 77% response rate) committed 364 hours
      (interquartile range 228-512 hours) to CME per year. Surgeons working at tertiary
      referral teaching hospitals were twice as likely as those working in other types
      of hospital to report spending more than 12 hours per month on CME (OR 2.1, 95%
      CI: 1.4-3.1). Overall, reading accounted for 17% of CME time and attending
      conferences a further 12%. Clinical audit accounted for significantly less CME
      time (3.5%) (both P < 0.001). Conferences were considered the single most useful
      form of CME by 28% (95% CI: 24-33%). Over half (55%, 95% CI: 50-59%) ranked
      reading as 1 of the 3 most useful types of CME, whereas significantly fewer so
      ranked clinical audit (6%, 95% CI: 4-9%) (chi2 = 230.8, 1 d.f., P < 0.001).
      CONCLUSION: Australian surgeons commit a considerable amount of time to CME, but
      much of this time is spent in passive educational activities. Development of
      acceptable and effective CME programmes will benefit both surgeons and their
      patients.

PMID- 16635122
TI  - Undergraduate public health education in UK medical schools - struggling to
      deliver.
AB  - INTRODUCTION: Recent policy initiatives in the United Kingdom (UK) have
      underlined the importance of public health education for health care
      professionals. We aimed to describe teaching inputs to medical undergraduate
      curricula, to identify perceived challenges in the delivery of public health
      teaching and strategies that may overcome them. METHODS: We undertook a cross
      sectional survey; questionnaires were sent electronically to 28 teaching leads in
      academic departments of public health in UK medical schools. These were followed
      up by telephone interviews. RESULTS: We obtained a 75% response rate. We found a
      great deal of variability between schools in teaching methods, curricular content
      and resources used. In 76% of medical schools, public health and clinical
      teaching were integrated to some extent. The proportion of teaching delivered as
      lectures is decreasing and that of self-directed learning is increasing. A range
      of methods is used to assess students and in 33% of schools these assessments
      contributed to final Medical School marks. More than half the medical schools had
      difficulty finding teachers and staffing levels had deteriorated in 55% of
      schools. Many interviewees felt that their contributions were undervalued. Few
      were aware of the level of funding received to support teaching. DISCUSSION:
      There is a need to increase the supply of well-trained and motivated teachers and
      combine the best traditional teaching methods with more innovative, problem-based
      approaches. Faculties need to share 'learning about what works' and teaching
      resources across medical schools as well as addressing a culture of neglect of
      teaching in some departments. Suggestions are made as to how undergraduate public
      health teaching can be strengthened.

PMID- 16635123
TI  - Strengths and weaknesses in the consultation skills of senior medical students:
      identification, enhancement and curricular change.
AB  - INTRODUCTION: This paper seeks to describe the consultation strengths and
      weaknesses of senior medical students, the explicit and prioritised strategies
      for improvement utilised in student feedback, and curriculum developments
      informed by this work. METHODS: Prospective, descriptive study of students on
      clinical placements in general practice. All were observed directly by 2
      assessors in consultation with 5 patients in a general practice setting.
      Performance was judged against 5 categories of consultation competence and 35
      component competences as contained in a modified version of the Leicester
      Assessment Package. Specific strategies for improvement were selected from a list
      of 69 previously formulated strategies. RESULTS: Data from 1116 students were
      included. The consultation competences identified most frequently as strengths
      related to interpersonal skills, while weaknesses were mainly in the domain of
      clinical problem-solving. The median number of key strengths identified per
      student was 5, with 5 additional but lesser strengths. A median of 3 key and
      lesser weaknesses were identified. The average number of strategies selected to
      address an identified weakness was 1.2. Students rated the assessment process and
      its impact very positively. CONCLUSION: The systematic assessment of the
      consultation competence of medical students by direct observation involving real
      patients is feasible and facilitates the 'educational diagnosis' of individuals
      and of their peer group. It has informed development of teaching and generated
      research hypotheses.

PMID- 16635124
TI  - The use of standardised patients to assess clinical competence: does practice
      make perfect?
AB  - CONTEXT: The use of standardised patients (SPs) is now an integral component of
      the United States Medical Licensing Examination (USMLE). This new requirement has
      caused more schools to include SP examinations (SPEs) in their curricula. This
      study reviews the effect of prior experience with SPs in a medical school
      curriculum on SPE pass rates. METHODS: This study reviewed the mean scores and
      pass rates on a 4-station SPE, comparing the performance of 121 US medical school
      graduates (USMGs) with that of 228 international medical graduates (IMGs). The
      analysis of USMGs' performance was based upon whether the resident had had
      previous exposure to an SPE during medical school, while the analysis of IMGs'
      performance was based upon whether the IMG had taken the Clinical Skills
      Assessment (CSA) for certification by the Education Commission for Foreign
      Medical Graduates. A distinction was made between those who had received prior
      exposure at Mount Sinai School of Medicine's Morchand Center, where the cases
      utilised were identical to those of the SPE, and those who had gained exposure
      elsewhere. RESULTS: Neither the mean scores of the IMGs and the USMGs nor the
      percentage who failed was significantly different relative to prior exposure to
      SPs. CONCLUSION: Prior exposure to SPs does not appear to have a positive effect
      on subsequent performance on an SPE unless similar or identical cases are used.
      However, the type and site of prior exposure limited the influence of the review.
      In view of the increased use of SPEs in medical schools, the content of prior
      exposure needs to be more fully established.

PMID- 16635125
TI  - Influence of clerkship experiences on clinical competence.
AB  - BACKGROUND: Clerkship experiences are considered crucial for the development of
      clinical competence. Yet whether there is a direct relationship between the
      nature and volume of patient encounters and learning outcomes is far from clear.
      Some evidence in the literature points towards the importance of clinical
      supervision on student learning, but the relationship between clinical
      supervision, patient encounters and student competence remains unclear.
      OBJECTIVES: This study aimed firstly to determine the variation in students'
      clinical experiences within and across sites; secondly, to identify the causes of
      this variation, and thirdly, to investigate the consequences of this variation on
      students' competence. METHODS: Clerkship students at 12 hospital sites recorded
      their patient encounters in logbooks. Site characteristics that might influence
      the variation in patient encounters were collected. Student competence was
      determined by 3 independent indicators: a practical end-of-clerkship examination;
      a theoretical end-of-clerkship examination, and an evaluation of professional
      performance. A model was developed to test the available clerkship data using
      structural equation modelling (SEM) software. RESULTS: Analysis of the logbooks
      revealed a large variation in the number of patients encountered by students. The
      average length of patient stay, number of patients admitted, and quality of
      supervision accounted partly for this variation. An increased number of patient
      encounters did not directly lead to improved competence. Quality of supervision
      turned out to be crucially important because it directly impacted student
      learning and also positively influenced the number of patient encounters.
      CONCLUSION: Monitoring the effectiveness of clerkship by merely asking students
      to keep a tally of the problems and diseases they encounter, without paying
      attention to the quality of supervision, does not contribute towards improving
      student learning.

PMID- 16635128
TI  - Behaviour change project for second-year medical students.

PMID- 16635129
TI  - Deepening compassion through the mirror of painting.

PMID- 16635130
TI  - Student 'moles': revealing the hidden curriculum.

PMID- 16635131
TI  - Impact of a novel evidence-based medicine curriculum.

PMID- 16635132
TI  - Sanitary assistance and cultural diversity.

PMID- 16635133
TI  - Evidence-based medicine curriculum: impact on medical students.

PMID- 16635134
TI  - Integrated teaching programme with student-centred case-based learning.

PMID- 16635135
TI  - Advocating programme evaluation in new problem-based learning schools.

PMID- 16635136
TI  - Integrating information management knowledge and skills in the pre-clinical
      curriculum.

PMID- 16635137
TI  - Discovering gender differences while teaching family genograms.

PMID- 16635138
TI  - The emergency department as an in vivo pathology laboratory.

PMID- 16635139
TI  - Expert system for pathology learning.

PMID- 16635140
TI  - Research by pre-clinical undergraduate medical students.

PMID- 16635141
TI  - Evolutionary medicine: a model for medical school introduction.

PMID- 16635142
TI  - Critical evaluation of drug promotion using role-plays.

PMID- 16635143
TI  - Clinical skills training in a resource constrained medical school.

PMID- 16635144
TI  - Video-enhanced problem-based learning to teach clinical skills.

PMID- 16635145
TI  - An encounter card to evaluate teachers in clerkship.

PMID- 16635146
TI  - A six-step approach to teaching physical examination.

PMID- 16635147
TI  - Introducing medical students to paediatric pain management.

PMID- 16635148
TI  - Plastic surgery and the undergraduate medical school curriculum.

PMID- 16635149
TI  - What every doctor should know about oral health.

PMID- 16635150
TI  - Interprofessional training of students in conducting ward rounds.

PMID- 16635151
TI  - A collaborative curriculum for medical and nursing students.

PMID- 16635152
TI  - Scoring an improvement in medical students' clinical notes.

PMID- 16635153
TI  - Competency pocket cards: an effective ambulatory assessment tool.

PMID- 16635154
TI  - Multidisciplinary teaching of the musculoskeletal physical examination.

PMID- 16635155
TI  - Reliability of adolescent standardised patients in assessing professionalism.

PMID- 16635156
TI  - Peer-level multiple source feedback for fitness to practice.

PMID- 16635157
TI  - Using residents as standardised patients in objective structured clinical
      examinations.

PMID- 16635158
TI  - CME programme leads to considerations in design concepts.

PMID- 16635159
TI  - Fully innovative training for general practice registrars.

PMID- 16635160
TI  - Doctors' perceptions of information utility in neonatal intensive care.

PMID- 16635161
TI  - Team-based learning: a strategy for interprofessional collaboration.

PMID- 16635162
TI  - Improving competencies through peer feedback in primary care settings.

PMID- 16635163
TI  - Neurological localisation course for postgraduate candidates.

PMID- 16635164
TI  - GREAT simulation debriefing.

PMID- 16635165
TI  - Research or audit? Ethical approval for medical student clinical projects.

PMID- 16635166
TI  - Late-onset ornithine transcarbamylase deficiency in male patients: prognostic
      factors and characteristics of plasma amino acid profile.
AB  - BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC)
      deficiency during adolescence or in adulthood has now been recognized. The aim of
      this study was to determine the prognostic factors that affect the prognosis of
      life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine
      of whom carried the R40H mutation and the other one carrying the Y55D mutation in
      the OTC gene, 32 demographic and laboratory data were first compared between
      survivors and non-survivors, using the unpaired t-test. The factors with
      significant difference were then subjected to multiple regression analysis.
      RESULTS: The factors that exhibited significant difference were: age at onset,
      concentration of plasma ammonium, blood pH, and concentrations of six amino acids
      in plasma. The multiple regression analysis then revealed concentrations of
      ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be
      significant prognostic factors. The amino acid profile in the 10 patients showed
      increases in glutamine, proline, lysine, valine and methionine, and decreases in
      serine, ornithine and arginine. There was an inverse correlation between the age
      at onset and the level of the residual hepatic OTC activity. CONCLUSION: The
      results implied that: (i) the plasma amino acid profile was unique, in comparison
      to other liver diseases; (ii) the plasma concentration of each of the (mentioned
      above) six amino acids was a significant predictor of prognosis; and (iii)
      suppression of protein catabolism, as suggested by the higher concentrations in
      isoleucine and leucine in the non-survivors, prevention of glutamine-induced
      brain edema, correction of alkalosis, and supplementation with ornithine or
      arginine may improve the prognosis of life.

PMID- 16635167
TI  - Successful uses of magnesium sulfate for torsades de pointes in children with
      long QT syndrome.
AB  - BACKGROUND: Administration of magnesium sulfate (MgSO4) is an effective and safe
      treatment for torsades de pointes (TdP) associated with acquired long QT syndrome
      (LQTS) in adults. As for children, there are few reports focusing on it. The
      authors discuss the efficacy of MgSO4 for TdP in children with congenital and
      acquired LQTS. The authors also discuss the optimal administration dosage and
      serum magnesium (SMg) concentration during MgSO4 therapy. METHODS: The authors
      studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the
      seven children, five were congenital LQTS and two were acquired LQTS. A bolus
      injection of MgSO4 was given intravenously over 1-2 min followed by continuous
      infusion for the next 2-7 days. RESULTS: Of the seven patients, six responded
      completely to the initial bolus. The bolus dosage was 5.9 +/- 3.8 mg/kg (range,
      2.3-12 mg/kg) in these six, and the other remaining one (neonate with congenital
      LQTS) required a total of 30 mg/kg until complete abolishment. The continuous
      infusion was given at rates of 0.3-1.0 mg/kg per h and patients did not show
      recurrence of TdP. The SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL)
      immediately after bolus injection. The mean corrected QT (QTc) interval before
      and after bolus injection did not show significant difference. CONCLUSION:
      Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and
      MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus
      dosage, infusion rates and SMg concentration were 3-12 mg/kg, 0.5-1.0 mg/kg per h
      and 3-5 mg/dL, respectively.

PMID- 16635168
TI  - Interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha levels in
      children with sepsis and meningitis.
AB  - BACKGROUND: Cytokines are thought to be important endogenous mediators of the
      host immune response to infection. The purpose of the present study was to
      evaluate the utility of serum levels of interleukin (IL)-1alpha, IL-6 and tumor
      necrosis factor (TNF)-alpha in the prediction and differentiation of sepsis and
      meningitis in children. METHODS: Blood was collected from 50 children admitted to
      hospital for suspicion of infection. On the basis of predetermined criteria and
      investigation, the children were classified into sepsis (n = 30) and meningitis
      (n = 20) groups, as well as into healthy controls (n = 24) and non-infected sick
      controls (n = 12). The sepsis group was subdivided according to culture results
      into S1 (proven sepsis, n = 11) and S2 (clinical sepsis, n = 19). Serum IL
      1alpha, IL-6 and TNF-alpha were measured by enzyme-linked immunosorbent assay
      (ELISA) while C-reactive protein (CRP) was measured by nephelometer. RESULTS: In
      non-infected sick controls, sepsis and meningitis groups, levels of CRP (P <
      0.001, P < 0.05 and P < 0.01, respectively), IL-1alpha (P < 0.001 for all), and
      IL-6 (P < 0.01, P < 0.001, P < 0.001, respectively) were significantly elevated
      compared to healthy controls. In sepsis, levels of IL-1alpha increased in the S2
      subgroup (P < 0.001) and IL-6 increased in the S1 and S2 subgroups (P < 0.05, P <
      0.001, respectively) compared with healthy controls. In meningitis, IL-1alpha had
      the highest sensitivity and negative predictive value, while IL-6 had the highest
      specificity and positive predictive value in non-infected sick controls, sepsis
      and meningitis groups. CONCLUSION: Interleukin-1alpha, IL-6 and CRP are increased
      in non-infected sick controls, sepsis and meningitis patients but it is not
      possible to differentiate between them. IL-1alpha had the highest sensitivity in
      meningitis while IL-6 had the highest specificity in prediction of sepsis and
      meningitis and their assessment together may improve accuracy in the diagnosis of
      childhood infection.

PMID- 16635169
TI  - Oral hypertonic glucose solution in the treatment of infantile colic.
AB  - BACKGROUND: Safe and effective treatment of infantile colic (IC) has not yet been
      determined. In this study, the authors aimed to investigate the efficiency of 30%
      glucose solution in the treatment of IC. METHODS: A total of 25 infants diagnosed
      as typical IC were given 1 mL of 30% glucose solution or sterile water for 4 days
      consecutively, in a randomized, double blind crossover trial. The effect was
      measured by parents' scoring. RESULTS: Parents reported varying degrees of
      improvement in 16 infants (64%) given glucose solution, and in 12 infants (48%)
      given placebo. Comparison of treatment modalities were statistically significant
      (P = 0.031). There was no side-effect during treatments. CONCLUSION: The present
      study revealed that 30% glucose was effective in the treatment of IC. Since oral
      glucose solution is natural, safe, cheap and easily achievable, it might be
      considered as an alternative therapy.

PMID- 16635170
TI  - Bone mineral density in malnourished children without rachitic manifestations.
AB  - BACKGROUND: The purpose of this study was to determine bone mineral density (BMD)
      of lumbar spine in malnourished children without rachitic manifestations, before
      and after dietary treatment and vitamin D supplementation, and to compare with
      healthy children of the same community. METHODS: The subjects were 41 children
      with malnutrition and 21 healthy controls. None of the children had clinical,
      biochemical and/or radiological rickets features. The patients had moderate 15
      and severe 26 malnutrition according to Gomez's criteria. Using the Wellcome
      Classification, marasmus was diagnosed in 16 children, kwashiorkor in 10
      children. The children with malnutrition were given vitamin D supplementation.
      RESULTS: BMD was lower in children with malnutrition than in controls (P < 0.01).
      Mineralization significantly effected the severity of malnutrition (P < 0.01).
      BMD in kwashiorkor was similar to that of marasmus. The mean BMD level of infants
      receiving 400 IU of vitamin D daily was similar to that of infants receiving 800
      IU of vitamin D daily at the beginning of treatment. In two supplementation
      groups, the BMD gradually increased during the first 3 months of treatment, but
      this increase in the infants receiving 800 IU of vitamin D daily was
      significantly higher than that in the infants receiving 400 IU of vitamin D
      daily. CONCLUSION: Measurements of BMD in children with malnutrition, especially
      severe malnutrition, are to be recommended in the initial assessment of the
      severity of osteopenia and in the follow up to monitor the response to therapy.
      Children with malnutrition should be given 800 IU of vitamin D daily. The loss of
      BMD must be accepted as a complication of malnutrition.

PMID- 16635171
TI  - Reliability of the functional independence measure for children in normal Thai
      children.
AB  - BACKGROUND: The Functional Independence Measure for children (WeeFIM) is a new
      instrument for evaluating functionality in disabled children aged 9-100 months.
      It was developed to determine a child's functional capacity and performance. With
      no baseline information about Thai children, it is difficult to assess whether a
      patient is initially high or low with respect to function. METHODS: The aim of
      this study, therefore, was to evaluate the interrater, intrarater reliability and
      appropriateness of the use of the WeeFIM and to establish a normative data
      profile suitable for Thai children. The WeeFIM is an instrument used to assess
      independence in self-care, sphincter control, transfer, locomotion,
      communication, and social cognition. RESULTS: Direct interviews were conducted in
      the communities for 569 normal Thai children (289 girls and 280 boys) aged 6-100
      months. The interrater and intrarater reliability scores were examined. The
      WeeFIM total and domain scores increased progressively with age. Intraclass
      correlation coefficients for the reliability for the WeeFIM domain score ranged
      from 0.90 to 0.99. Total WeeFIM intraclass correlation coefficients values were
      greater than 0.97 for all analyses. The authors classified the 18 items into six
      groups according to the degree of correlation with age. Most items were highly
      correlated with age as indicated by a Spearman's correlation coefficient greater
      than 0.8. The interrater and intrarater reliability of the WeeFIM subscores was
      high. CONCLUSION: The current study demonstrated that WeeFIM could be employed as
      a useful and reliable instrument for assessing functional independence for Thai
      children. Therefore, usage of WeeFIM with different age criteria for achieving
      independence should be adopted. Normative functional independence measures for a
      large group of Thai children will enhance the knowledge base about their
      development measurement and provide a database for future investigations on
      clinical population in Thailand.

PMID- 16635172
TI  - The effects of television food advertisement on children's food purchasing
      requests.
AB  - BACKGROUND: Children's eating habits and their food consumption have direct
      relations with obesity, diabetes, cancers, hypertension and coronary heart
      disease. Television advertisements directly affect children's eating habits and
      their food consumption. This study was conducted in order to examine television
      advertisements and children's food consumption while watching television and
      their desire to purchase goods that they see on television advertisements.
      METHODS: In the first stage of the study, content analysis of the television
      advertisements was conducted. In the second stage of the study, a questionnaire
      (check list) was developed in order to examine children's food consumption while
      watching television and their purchasing requests while shopping in the
      supermarket. It was given to 347 mothers who have children aged between 3 and 8
      years. RESULTS: When the results of the study were examined it was found that the
      time devoted to children's programs was approximately 121 min and the
      advertisements during this period were approximately 35 min. A total of 344 of
      the 775 television advertisements shown were related to food. It was also found
      that most of the food advertisements were about candy/chocolate, chips, milk and
      milk products such as cheese, yoghurt, and breakfast cereals. The results also
      revealed that 89.6% of the children either drank or ate something while watching
      television and the food they consumed most while watching television were fruits,
      soft drinks, popcorn/nuts, cake, chips and candy/chocolate. The results also
      revealed that 40.3% of the children asked their parents to purchase the goods
      that they saw on the television advertisements and that 8.9% of them argued with
      their parents and/or cried in order for their parents to buy that particular
      product. It was found that the children tended to request more sweetened products
      such as candy, ice-cream, biscuit, cake or soft drinks. CONCLUSION: More than
      half of the food presented in television advertisements were rich in fat and
      sugar. Children ask their parents to buy the goods they see on television
      advertisements both while watching television and while shopping. Television
      advertisements especially affect young children's unhealthy food consumption.

PMID- 16635173
TI  - Sedation with intravenous ketamine and midazolam for painful procedures in
      children.
AB  - BACKGROUND: Children often require relief of pain and anxiety when undergoing
      painful procedures. The purpose of this study is to evaluate the effectiveness
      and safety of painful pediatric procedures performed by pediatric intensivist,
      using the combination of intravenous ketamine and midazolam for sedation and
      analgesia. METHODS: The records of the patients who received intravenous ketamine
      midazolam combination for painful procedures in the pediatric sedation unit of a
      university hospital over a 3 year period were retrospectively reviewed to
      determine indications, dosing, assessment of the level of sedation, adverse
      events, and recovery time for each procedural sedation and analgesia. RESULTS: A
      total of 227 children aged 4 months to 18 years were admitted to the pediatric
      sedation unit for a total of 356 procedures. The indications for procedural
      sedation and analgesia included bone marrow aspiration or biopsy (50.8%), central
      venous catheter insertion (27%), and others (22%). A total of 46 adverse events
      (12.9%) were observed. These adverse events included SpO2 below 85% without apnea
      (n = 14), apnea (n = 3), transient stridor (n = 2), hypertension and tachycardia
      (n = 8), hypersalivation (n = 6), vomiting (n = 5), hallucinatory emergence
      reaction (n = 4), and rash (n = 4). There were no adverse outcomes attributable
      to ketamine and midazolam combination. CONCLUSION: Skilled pediatric intensivists
      can safely and effectively administer ketamine and midazolam to facilitate
      painful procedures outside the operating room setting.

PMID- 16635174
TI  - High-dose mizoribine treatment for adolescents with systemic lupus erythematosus.
AB  - BACKGROUND: In treating pediatric patients with systemic lupus erythematosus
      (SLE), it is necessary to quickly attain remission to avoid sequelae in various
      organs and to maintain it over a long period. However, to maintain remission, the
      prolonged use of immunosuppressants which have various adverse effects, is often
      necessary in addition to steroids, and complications due to such
      immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at
      150 mg/day divided into two or three doses has been recommended, but while this
      regimen has been safe, its efficacy has not been satisfactory. However, MZR
      produces effects dose-dependently, and the dose recommended to date may have been
      insufficient for the treatment of children with SLE. METHODS: The authors
      administered oral MZR at 300 mg/day in two divided doses, which is twice the
      conventional dose for adults, to five adolescents with SLE. Three of these five
      were markedly steroid-dependent patients and two had previously been treated with
      steroids only. Thereafter, the authors evaluated the safety and efficacy of the
      regimen by following the patients for at least 7 months after the beginning of
      treatment. RESULTS: Patients 1 and 2 had been treated with prednisolone (PSL) and
      cyclosporine (CyA), but as the duration of CyA administration became long, it was
      replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient
      3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but
      the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and
      5, the control of symptoms with PSL alone was judged to be difficult, and
      concomitant administration of MZR at 300 mg was started. This resulted in a
      decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 microg/mL or higher in
      all five patients, and the efficacy of the treatment was satisfactory. Concerning
      side-effects, hyperuricemia was noted in two patients, but it was resolved in one
      of them by reducing the dose of MZR and in the other spontaneously while the
      treatment was continued. Temporary exacerbation of hair loss was observed in two
      patients, but it disappeared in both of them after a few months. CONCLUSION: MZR
      could be administered at a high dose effectively and safely. However, monitoring
      of the serum uric acid level was necessary. High-dose MZR therapy showed an
      efficacy and safety that would warrant its application to steroid-dependent
      pediatric patients with SLE.

PMID- 16635175
TI  - Effect of a structured asthma education program on hospitalized asthmatic
      children: a randomized controlled study.
AB  - BACKGROUND: The aim of this study was to compare the effectiveness of an
      intensive asthma education program (group B) with that of a standard asthma
      education program (group A). METHODS: A prospective randomized single blinded
      study was conducted in the pediatric department of a public hospital in Hong
      Kong. Children aged 2-15 years admitted to the pediatric department with an acute
      attack of asthma were recruited. A standard asthma education program (group A) or
      an intensive asthma education program (group B) for children were offered. The
      main outcome measures include the number of visits to the emergency department
      and the number of hospitalization for asthma during the 3 month follow-up period.
      RESULTS: A total of 45 children were in group A and 55 in group B. Group B had
      statistically significant reductions in the number of visits to the emergency
      department and the number of hospitalizations. Drug compliance was also
      significantly improved in group B. Parents' satisfaction rate was also higher in
      group B. CONCLUSION: The intensive asthma education program might be more cost
      effective than the standard asthma education program in the management of
      asthmatic children admitted to hospital in Hong Kong.

PMID- 16635176
TI  - A case of intractable methicillin-resistant Staphylococcus aureus sepsis after an
      operation for tetralogy of Fallot that was successfully resolved by combined
      treatment with vancomycin and urokinase.

PMID- 16635177
TI  - Coexistent Takayasu arteritis and erythrokeratodermia variabilis: a case report.

PMID- 16635178
TI  - A new low-penetrance TNFRSF1A mutation causing atypical periodic fever.

PMID- 16635179
TI  - Neonatal cecal cystic duplication mimicking intussusception.

PMID- 16635180
TI  - Iron removal with phlebotomy and recombinant human erythropoietin in secondary
      hemochromatosis after allogeneic bone marrow transplantation.

PMID- 16635182
TI  - Bilateral ovarian teratomas successfully treated by ovary-conserving technique.

PMID- 16635181
TI  - Successful recombinant erythropoietin therapy for a developing anemic newborn
      with hereditary spherocytosis.

PMID- 16635183
TI  - Neonatal suppurative parotitis possibly associated with congenital
      cytomegalovirus infection and maternal methyldopa administration.

PMID- 16635184
TI  - An unusual case of Type IV(A) choledochal cyst with subaortic ventricular septal
      defect.

PMID- 16635185
TI  - Guidelines for the use of palivizumab in infants and young children with
      congenital heart disease.

PMID- 16635186
TI  - Sharing responsibilities to make evidence-based practice clinically feasible.

PMID- 16635187
TI  - Enhancing intervention fidelity: a means of strengthening study impact.
AB  - PURPOSE: Intervention studies that address the goals of the Healthy People
      initiative are increasing, and many focus on health concerns of children and
      adolescents. The purpose of this paper is to present strategies and discuss the
      rationale for including intervention fidelity in study design. CONCLUSION:
      Researchers need to verify that their interventions were delivered as designed
      (intervention fidelity), and that variations from the design can be assessed.
      Infidelity can result in non-significant findings that are not due to the study
      design but rather to elements that affected the intervention delivery.
      IMPLICATIONS: Addressing intervention fidelity in study design supports the
      researcher's conclusion about associations between intervention and outcomes and
      helps reduce premature abandonment of potentially useful interventions.

PMID- 16635188
TI  - Methods of continuing professional education preferred by Irish pediatric nurses.
AB  - PURPOSE: To explore the continuing professional education (CPE) of pediatric
      nurses in Ireland and establish if and in what ways pediatric nurses are taking
      part in CPE as well as factors that might assist or hinder pediatric nurses in
      undertaking CPE. DESIGN AND METHODS: A stratified random sample of 205 registered
      children's nurses (RCNs) completed a questionnaire. RESULTS: RCNs in Ireland use
      a variety of methods of CPE, the most popular being journal reading, while the
      least popular method is the use of computerized journal databases and the
      internet. Many RCNs appear to lack the computer skills necessary to utilize these
      methods of CPE. PRACTICE IMPLICATIONS: The favored methods of CPE by RCNs need to
      be utilized and promoted in the practice setting in order to ensure RCNs are up
      to date in the provision of quality care to pediatric patients.

PMID- 16635189
TI  - Formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA):
      a critical review of the research.
AB  - PURPOSE: To summarize results of randomized controlled trials (RCTs) evaluating
      growth, cognitive, neurological, and visual development of term infants
      supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA). DESIGN
      AND METHODS: The Boyack and Lookinland Methodological Quality Index (MQI) was
      used to evaluate data from RCTs identified from multiple data bases. RESULTS: Six
      of ten studies found the addition of DHA and ARA to have no significant effect on
      infant development. PRACTICE IMPLICATIONS: More expensive formula with endogenous
      DHA and ARA is not necessary. Results from longer studies currently underway will
      be beneficial.

PMID- 16635191
TI  - The effects of weapons of mass destruction on children.
AB  - PURPOSE: Children are especially vulnerable to the effects of chemical and
      biological weapons of mass destruction (WMD) because of physiologic,
      pharmacologic, and developmental characteristics. Presentation of signs and
      symptoms of exposure to biological and chemical agents are similar to those seen
      in adults. Pediatric considerations for decontamination and treatment of child
      victims of biological and chemical agents are discussed. CONCLUSION: As front
      line providers, nurses need to be aware of potential agents, their uses and
      effects as WMD, and recommended treatments. PRACTICE IMPLICATIONS: Understanding
      the additional physiologic and situational needs of children, nurses can optimize
      the survival and outcomes of children when disaster strikes.

PMID- 16635192
TI  - Caring for child victims: countering the effects of domestic violence.

PMID- 16635193
TI  - Addressing the psychosocial needs of children following disasters.

PMID- 16635194
TI  - 100,000 lives campaign and the application to children.

PMID- 16635195
TI  - Attention to child development: a key piece of family-centered care for cardiac
      transplant recipients.

PMID- 16635196
TI  - Welcome to school health.

PMID- 16635198
TI  - The school nurse's role in prevention of student use of performance-enhancing
      supplements.
AB  - An alarming trend in the United States is the use of performance-enhancing
      supplements by children and adolescents. These widely available over-the-counter
      products, often marketed as natural substances, are not regulated by the Food and
      Drug Administration and are thus widely available. High school and even middle
      school students are using these supplements because they are misled into thinking
      that supplements will enhance their athletic skills resulting in an improvement
      in their performance. Yet, the safety and long-term effects of these supplements
      have not been established in reputable or prevalent studies. School nurses have a
      unique opportunity and even an ethical responsibility to help in efforts to
      address this growing trend. Specific roles for the school nurse include serving
      as a student advocate for the health and safety of children and adolescents;
      identifying at-risk students; forming partnerships with teachers, parents,
      students, coaches, athletic trainers, and local health care providers; evaluating
      and refining health-oriented curricula; collecting and disseminating new
      knowledge; and staying abreast of new findings.

PMID- 16635199
TI  - An exploration into the internal dynamics of a school-based mental health
      collaboration.
AB  - Schools are moving toward a human service approach that encompasses the physical
      and mental needs of its students on top of the traditional role of educating.
      School-based collaboratives are one delivery model that satisfies this expanding
      role. Lacking in the research on this emerging setting, particularly in the realm
      of mental health, is information that gives insight into the interactions that
      occur between collaborative partners who may have opposing aims. This study
      explores 2 outcome measures, timeliness of implementation of the treatment plan
      and parental satisfaction with the treatment plan and the influence of the
      professional view of collaborative partners on these outcomes. Archival data were
      collected from patient charts on 101 Hispanic students, 73.3% of who were male
      and the sample mean age was 11.3 years. These data were analyzed using multiple
      regression techniques. Results revealed that time to implementation was impacted
      by the diagnosis alignment of participating partners, a proxy for professional
      view, as was parental satisfaction. Satisfaction was not influenced by
      timeliness, indicating alternative outcome desires.

PMID- 16635200
TI  - Results from the 2004 Michigan Farm-to-School Survey.
AB  - The purpose of this study was to investigate Michigan school food service
      directors' interest in, and opportunities and barriers to, implementing a farm-to
      school program. Farm-to-school may be a timely and innovative approach to
      improving the school food environment and helping food service directors meet
      their nutrition goals for school meals. Health and agriculture advocates have
      recognized the importance of farm-to-school in addressing health issues and
      creating opportunities for farmers and rural communities. Research subjects were
      664 food service directors representing school districts across Michigan.
      Respondents (n = 383) reported a high degree of interest in sourcing food from
      local producers (73% reported being very interested or interested). Interest was
      significantly augmented (83%) when respondents were asked to assume that these
      foods were available through current vendors. Interest was independent of
      free/reduced lunch participation rate or school district location (rural,
      suburban, urban location). Food service directors expressed diverse motivations
      for their interest in farm-to-school, including supporting the local economy and
      community; accessing fresher, higher-quality food; and potentially increasing
      students' fruit and vegetable consumption. The most frequently reported barriers
      and concerns included cost, federal and state procurement regulations, reliable
      supply, seasonality of fruits and vegetables, and food safety. Michigan school
      food service directors appear ready to make linkages with local agriculture.
      However, there is need to address the concerns and barriers through education;
      inclusion of community partners, such as current vendors; funding; and state and
      federal policies that support local purchasing.

PMID- 16635201
TI  - Health behaviors of school-age children: evidence from one large city.
AB  - Relatively little is known about risk behaviors of elementary school children. A
      recent evaluation of a comprehensive school health education curriculum provided
      an opportunity to survey elementary school children about their perceived health
      status, knowledge, attitudes, health self-efficacy, and health and risk
      behaviors. For the evaluation, a total of 4273 surveys were completed by 2
      cohorts of school children, grades 2 and 4, in 24 schools in a large urban school
      district during the spring semesters of 2002; the cohorts were surveyed a second
      time when they were in third and fifth grade in spring 2003. Older children
      scored higher than younger ones on factors generally associated with improved
      health behaviors (such as health knowledge and refusal skills); yet, they scored
      lower than younger children on healthy behaviors, especially risk behaviors and
      those things presumed to be associated with later adolescent risk taking. The
      interrelationships among behavior, knowledge, age, and school-level attributes
      are explored. As health knowledge, refusal skills, and other protective factors
      increase, health behaviors improve slightly, but the most important factor in
      explaining health behaviors is grade level. This article points to the need to
      study the development of risk behaviors throughout elementary school and the need
      for additional work on the measurement of risk behaviors during the elementary
      school years.

PMID- 16635202
TI  - Predictors of suicidal ideation among high school students by gender in South
      Korea.
AB  - The purpose of this study was to examine the evidence to determine if there are
      gender differences in suicidal ideation of adolescents. This study examined the
      main effect of risk factors from 5 domains and protective factors from 1 domain
      in relation to suicidal ideation by gender and identified the most important
      predictors of suicidal ideation for males (N = 654) and females (N = 658). This
      study was a cross-sectional survey, and data were collected through self-report
      questionnaires. In the univariate analysis, especially, risk factors from
      behavioral variables and psychosocial-environmental variables appeared to be
      gender skewed. For males, all behavioral variables were predictive of suicidal
      ideation. For the females, unlike the males, Wang-tta or victim of bullying
      behavior and sexual orientation as behavioral variables were predictive of
      suicidal ideation. For males, parental divorce and parental alcohol abuse as
      psychosocial-environmental variables were predictive of suicidal ideation. For
      the females, again unlike for the males, all the psychosocial-environmental
      variables were not predictive of suicidal ideation. The most important predictors
      of suicidal ideation for males as a result of the multivariate analysis were
      history of suicidal attempt, depression, hostility, smoking, parental alcohol
      abuse, communication with friends, and self-esteem. The most important predictors
      of suicidal ideation for females as a result of the multivariate analysis were
      depression, hostility, sexual orientation, and self-esteem. These results would
      indicate that an effective suicide screening and prevention program for
      adolescents should consider gender differences.

PMID- 16635203
TI  - Prevalence of risk for type 2 diabetes in school children.
AB  - According to the Centers for Disease Control and Prevention, 1 in 3 children born
      in 2000 in the United States will become diabetic. The odds are higher for
      African American and Hispanic children as nearly 50% of them will develop
      diabetes. Random screening is not effective in identifying children at risk for
      type 2 diabetes mellitus (T2DM); therefore, there is a need to apply screening
      strategies that guide the development of appropriate primary prevention efforts.
      To assess the prevalence of risk factors for T2DM, 1066 fifth-grade children were
      screened using American Diabetes Association guidelines. Overall, 22.6% were
      found at risk; African American and Hispanic children were almost 8 times more
      likely to be at risk when compared to Caucasians (odds ratio = 7.41 and 7.87).
      Children who reported watching TV/playing video games 2 or more hours/day were
      73% more likely to be at risk. Children identified to be at risk were referred to
      their primary care provider and were invited to participate in a counseling
      session. The environmental risk factors for T2DM identified in this study are
      modifiable and should be targeted in preventive interventions at the school and
      community level to reduce overweight and consequently prevent T2DM in children,
      especially among minority children.

PMID- 16635204
TI  - Racial disparities in tobacco use and social influences in a rural southern
      middle school.
AB  - This study investigated racial differences of tobacco use and social exposure to
      tobacco products in a sample of middle school students. Questionnaires were
      administered in January 2005 to 290 students in a Mississippi Delta-area middle
      school. The participants were 51.0% female and 56.6% African American. Unadjusted
      odds ratios revealed that Caucasian students were statistically more likely than
      were African American students to (1) have ever tried smoking, (2) have ever been
      a daily smoker, (3) have smoked in the past 30 days, (4) live with someone who
      smokes, (5) have seen a parent or guardian smoke, and (6) have friends who smoke.
      In contrast, African Americans were more likely to report "no one is allowed to
      smoke" in their home. Caucasian females had the highest rates of smoking, as well
      as the highest exposure to social smoking behaviors. This study not only showed
      that Caucasians were indeed smoking more but also that African American
      adolescents do not have the same exposure to social smoking, particularly African
      American females. Of particular interest was why the differences eventually
      dissipate and smoking rates are virtually the same in adulthood. A greater
      understanding of the impact of exposure to tobacco use on an adolescent's own
      tobacco use is vital to prevention efforts, especially in regard to racial
      differences. Future research on youth tobacco prevention and cessation programs
      should focus on sociocultural and racial differences in the development of
      tobacco use in adolescents.

PMID- 16635205
TI  - Comparison of vaginal cytokine collection methods.
AB  - OBJECTIVE: The objective of our study was to correlate the interleukin-6 (IL-6)
      concentrations detected in patient-collected specimens with provider-collected
      specimens and compare the reproducibility of the methods. STUDY DESIGN: All
      enrolled participants underwent pelvic examination with collection of cytokine
      samples by the provider and also collected samples themselves using vaginal
      swabs. The order of sample collection was randomly assigned. All samples were
      frozen at -80 degrees C for batch analysis. A commercial enzyme-linked
      immunosorbent assay was used to determine the concentrations of IL-6 in all
      samples. RESULTS: IL-6 concentrations from wicks and swabs were correlated in a
      linear fashion (r = 0.67, P < 0.001). IL-6 concentrations in the two swabs (r =
      0.94, P < 0.001) and the two wicks (r = 0.71, P < 0.001) were correlated in a
      linear fashion, although there was more variability in wick specimens.
      CONCLUSION: IL-6 concentrations can be reproducibly measured using either method.
      The ease of patient swab collection and the correlation with provider-collected
      specimens may make frequent assessment of the vaginal cytokine environment more
      acceptable to patients.

PMID- 16635206
TI  - Identification of evolutionary conserved mouse sperm surface antigens by human
      antisperm antibodies (ASA) from infertile patients.
AB  - PROBLEM: The presence of antisperm antibodies (ASA) in semen may impair sperm
      function leading to immunological infertility. The aim of the study was to
      identify the evolutionary conserved antigens on mouse sperm surface that react
      with human ASA in order to study the mechanism of autoimmune infertility. METHODS
      OF STUDY: The binding of human ASA to mouse sperm was investigated by means of
      indirect immunofluorescence. 2D-electrophoresis was applied to separate the
      biotin-labelled mouse membrane proteins using isoelectric focusing followed by
      polyacrylamide gel electrophoresis. Cognate antigens of ASA from seminal plasma
      of infertile patients were analysed by Western blotting. Performing avidin-blots
      it was detected which of the proteins recognized were sperm surface proteins. The
      spots of interest were analysed by means of mass spectrometry. RESULTS: ASA bound
      most frequently (36%) to the post-acrosomal region and to the midpiece of mouse
      spermatozoa. About 30% of ASA recognized apo lactate dehydrogenase (LDHC4) as a
      cognate antigen, 30% voltage-dependent anion channel (VDAC2). ASA of 20% bound to
      outer dense fibre protein and 20% of samples recognized glutathione S-transferase
      mu5. CONCLUSIONS: Human ASA bound to specific cognate antigens of mouse
      spermatozoa, offering the possibility to study their functional relevance in the
      mouse model.

PMID- 16635207
TI  - Alloimmune and autoimmune background in recurrent pregnancy loss - successful
      immunotherapy by intravenous immunoglobulin.
AB  - PROBLEM: Immunotherapies [leukocyte immunization, intravenous immunoglobulin
      (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have
      still controversial results in most clinical trials. A selection of these
      patients would be advantageous for higher efficacy. METHOD OF STUDY: A complex
      immunological panel assay was offered to patients with reproductive failure
      without any other known cause. We focused here on the cellular immunological
      parameters. RESULTS: High cytotoxic T lymphocyte precursor frequency and cell
      mediated cytotoxic activity and a rather high natural killer cell activity were
      found in alloimmune RSA patients. Thirty-two patients were investigated by
      immunological assays and in 78% of the women an alloimmune background could be
      defined. The efficacy of IVIG treatment was 96% in this group. CONCLUSIONS: The
      novel cellular immunological assays proved to be favourable for the indication of
      RSA patients and showed the usefulness of this selection process for effective
      immunotherapy.

PMID- 16635208
TI  - IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are
      related to low fertilization rate of their oocytes.
AB  - PROBLEM: Patients undergoing in vitro fertilization and embryo transfer (IVF-ET)
      failures show an increased incidence of antiphospholipid antibodies (aPL) in
      their blood. The physiological manifestations of aPL in this patient group are
      nonetheless controversial. Pathological effects of aPL on embryos in vitro have
      been documented. We questioned whether aPL if found in follicular fluids (FFs)
      could result in embryonic damage. METHOD OF STUDY: Blood from 44 patients with
      three or more IVF-ET failures were tested by enzyme-linked immunosorbent assays
      (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA aPL. Both the 29
      aPL-positive and 15 aPL-negative patients gave permission for FF collection
      during their next IVF-ET attempt for additional aPL determinations. RESULTS:
      Patients with no aPL in their blood, had no aPL in their FFs. Patients with IgG
      and/or IgM aPL in their blood had IgG but not IgM in their respective FFs.
      CONCLUSIONS: The presence of IgG aPL in FFs and increased infertility length were
      significantly related to lower fertilization rates, independently. Follicular
      fluid IgG aPL appears as a risk factor in association with successful IVF-ET
      outcomes.

PMID- 16635209
TI  - Expression profile and clonality of T-cell receptor beta variable genes in normal
      human endometrium.
AB  - PROBLEM: In spite of their key immunological role, alphabeta+ T cells residing in
      endometrium have not been extensively explored. We analyzed here expression
      profile of TCRBV genes in normal human endometrium compared with peripheral
      blood. METHODS: Samples were taken from normal reproductive women. RT-PCR using
      BV-gene specific primers was performed on blood and endometrial samples. After
      blotting, hybridization with radiolabelled probe and autoradiography, relative
      expression of each TCRBV family was determined. Clonal expansions of the over
      expressed genes were assessed by CDR3 length polymorphism. RESULTS: Only one gene
      (TCRBV7) was expressed significantly and two other genes marginally more in the
      endometrium compared with blood. All three TCRBV genes examined showed a rather
      restricted pattern in the endometrium in contrast to polyclonal patterns in the
      blood. CONCLUSION: Our results stress the similarities between T cells residing
      in different mucosal tissues and provide a basis for future investigations about
      endometrial T cells and their antigen specificities in gynecological problems.

PMID- 16635210
TI  - Multiple thrombophilic gene mutations rather than specific gene mutations are
      risk factors for recurrent miscarriage.
AB  - PROBLEM: Recurrent miscarriage is a heterogeneous condition. While the role of
      acquired thrombophilia has been accepted as an etiology of recurrent miscarriage,
      the contribution of specific inherited thrombophilic genes to this disorder has
      remained controversial. We compared the prevalence of 10 thrombophilic gene
      mutations among women with a history of recurrent miscarriages and fertile
      control women. METHOD OF STUDY: A total of 150 women with a history of two or
      more recurrent pregnancy losses and 20 fertile control women with no history of
      pregnancy losses had buccal swabs taken for DNA analyses of 10 gene mutations
      [factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin
      G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b (L33P),
      MTHFR C677T, MTHFR A1298C]. The prevalence of these mutations was compared
      between women experiencing recurrent miscarriage and controls. RESULTS: No
      differences in the frequency of specific gene mutations were detected when women
      with recurrent miscarriage were compared with control women. However, the
      prevalence of homozygous mutations and total gene mutations among patients with
      recurrent miscarriage was significantly higher than among controls. Homozygous
      mutations were found in 59% of women with a history of recurrent pregnancy loss
      contrasted to 10% of control women. More than three gene mutations among the 10
      genes studied were observed in 68% of women with recurrent miscarriage and 21% of
      controls. CONCLUSION: Inherited thrombophilias are associated with recurrent
      miscarriage. This association is manifest by total number of mutations rather
      than specific genes involved.

PMID- 16635211
TI  - Uterine (CD56+) natural killer cells recruitment: association with decidual
      reaction rather than embryo implantation.
AB  - PROBLEM: Whether decidual leukocyte recruitment and/or increase is primarily
      hormonally regulated or induced mainly by blastocyst implantation is a matter of
      debate. Thus, this study investigated the number and distribution of leukocyte
      populations, with emphasis on natural killer (NK) cells of uterine and peripheral
      type, within decidual tissue from women with decidualized endometrium both
      related and unrelated to pregnancy and those with ectopic decidua associated with
      intrauterine pregnancy, as well as in tubal implantation sites. METHOD OF STUDY:
      Immunohistochemical characterization of immune cells using antibodies to CD3,
      CD4, CD8, CD20, CD68, CD16, CD56, CD57, in formalin-fixed, paraffin-embedded
      tissue, and a quantitative analysis of these subpopulations was conducted in
      tissue blocks from four groups of patients: (i) 20 women with decidualized
      endometrium due to progestin therapy (i.e. not associated with gestation) (group
      Prog-D); (ii) 20 women with intrauterine pregnancy-associated ectopic decidua
      (seven in the Fallopian tube, five in the ovary, five in the uterine cervix, and
      three in the omentum) (group Ect-D); (iii) 20 women with spontaneous abortion who
      had an histologic sample of the decidua at the uterine implantation site (group
      Uter-D); and (iv) 20 consecutive patients who had had an ectopic tubal pregnancy
      (group Tub-Preg). Twenty gynecologic specimens with marked inflammatory reaction
      were used as controls (group Con). RESULTS: CD3+, CD4+, CD8+, CD68+ cells were
      detected in all tissue samples investigated. In contrast, CD20+ cells were
      detected in all samples in group Con, but only in 75%, 25%, 55% and 70% of groups
      Prog-D, Ect-D, Uter-D and Tub-Preg, respectively. In all tissue samples
      investigated, CD57+ and CD16+ cells were detected. Conversely, CD56+ cells were
      completely absent in 15 of 40 cases (37.5%) lacking decidual reaction (group Tub
      Preg, 7/20; group Con, 8/20) but were present in all cases showing decidual
      reaction. In contrast with CD56+ cells, CD57+ NK cells were more abundant in
      group Con than in the four study groups. CONCLUSIONS: CD56+ NK cells are closely
      related to decidua irrespective of its eutopic or ectopic location rather than to
      the implantation site. This suggests that the recruitment and/or increase of
      uterine NK cells into the uterus is not dependent on the physical presence of an
      implanting embryo but instead is controlled hormonally.

PMID- 16635212
TI  - Immunocontraception of Florida feral swine with a single-dose GnRH vaccine.
AB  - PROBLEM: Methods to limit fertility of feral swine are needed to reduce
      transmission of diseases and agricultural and ecosystem damage. Method of Study
      We evaluated a single-shot GnRH immunocontraceptive vaccine in both male and
      female feral swine for its effect on fertility and functional status of the
      reproductive tissues. Captive feral pigs were randomly assigned to receive 1000
      or 2000 microg GnRH-KLH vaccine treatments or no treatment. RESULTS: After 36
      weeks, none of the 2000-microg-treated females and only 20% of the 1000-microg
      treated females were pregnant. This corresponded to reduced serum progesterone,
      regressed tissues within the reproductive tract and lack of evidence for
      follicular development leading to ovulation. Males were less responsive to the
      vaccine than females, but more responsive to the lower dose of the vaccine than
      the higher dose. CONCLUSIONS: The single-shot GnRH vaccine is effective in
      controlling fertility of female feral swine and may be useful for population
      reduction.

PMID- 16635214
TI  - Living donor liver transplant--is the horse already out of the barn?

PMID- 16635215
TI  - FDA advisory committees: their purpose, how they work, and how you can become a
      member.

PMID- 16635216
TI  - Repeated pneumatic dilations as long-term maintenance therapy for esophageal
      achalasia.
AB  - INTRODUCTION: In esophageal achalasia, pneumatic dilations (PD) provide short
      term and long-term remission rates of 60-90% and 40-50%, respectively. The aim of
      this study was to evaluate the long-term efficacy of repeated PD as long-term
      maintenance therapy. PATIENTS AND METHODS: From 1992 to 2004, 150 patients with
      esophageal achalasia treated by PD were included in this retrospective study (78
      males, mean age 57 +/- 20 yr). PD were performed until remission was achieved
      (symptom score < or = 3, each item < 2) and subsequently when symptomatic
      recurrence occurred. A standardized symptoms questionnaire was sent to patients
      lost to follow-up. Results are expressed as mean +/- SD. RESULTS: Initial
      remission was achieved in 137 of 150 (91.3%) patients with 2.67 +/- 1.59
      dilations [range 1-12]. Failure and perforation rates were 7.3% (n = 11) and 1.3%
      (n = 2), respectively. After initial remission, 48 of 137 (35%) patients had
      recurrent symptoms; the probability to be in remission at 5 and 10 yr was 67% and
      50%, respectively. At the end of follow-up (45 +/- 38 months, ext. 2-144) 108 of
      137 (78.8%) patients were in remission. Among 112 patients whose symptoms could
      be treated by repeated PD (per protocol analysis), 108 (96.4%) were in remission
      (3.5 +/- 2.1 PD, ext. 2-12). In this group, the probability of being in remission
      after repeated PD at 5 and 10 yr was 96.8% and 93.4%, respectively. No
      pretherapeutic factor influenced long-term remission rate. The overall prevalence
      of gastroesophageal reflux was 34.7%. CONCLUSION: One-third of the patients with
      esophageal achalasia treated by PD will experience symptomatic recurrence during
      a 4-yr period. Long-term remission can be achieved in virtually all the patients
      treated by repeated PD according to an "on-demand" strategy based on symptom
      recurrence.

PMID- 16635217
TI  - Achalasia: should we or should we not follow the bag?
AB  - This article concerns the long-term therapeutic effect of pneumatic dilations
      (PDs) in achalasia. Specifically, it is a retrospective study that follows a
      large cohort of achalasia patients treated with PD. Efficacy and need for repeat
      PDs were determined utilizing a score obtained from measuring symptoms after PD.
      After PDs that resulted in symptomatic improvement, patients were followed at 6
      month intervals to determine the need for repeat PD. The major point of this
      article is that exacerbations of symptoms may occur in 35% of patients undergoing
      PD; however, follow-up at specific intervals using a symptom score to determine
      the need for repeat PD resulted in excellent long-term success. This article
      emphasizes the need for continued follow-up of achalasia patients following
      initial successful therapy.

PMID- 16635218
TI  - A COX-2-specific inhibitor plus a proton-pump inhibitor: is this a reasonable
      approach to reduction in NSAIDs' GI toxicity?
AB  - The two prevailing approaches to decrease risks of nonsteroidal anti-inflammatory
      drug (NSAID)-associated gastrointestinal (GI) events are the use of a COX-2
      inhibitor or co-therapy with a proton-pump inhibitor (PPI). A major limitation of
      each approach is that, in patients at the highest risk for NSAID-induced ulcers,
      neither treatment is effective when used as a stand-alone strategy. An important
      question is whether combination therapy with a COX-2 inhibitor plus a PPI has
      improved GI safety compared to a traditional NSAID plus a PPI. This study
      evaluated high GI risk patients who were taking, along with their NSAID or COX-2
      inhibitor, either the PPI, esomeprazole, or the placebo. It confirms that our
      current approach of adding PPIs to reduce NSAIDs' ulcer risks is an effective
      strategy. However, this study did not show a safety advantage for using a COX-2
      inhibitor instead of a traditional NSAID in high GI risk patients who take PPIs.
      Thus, there continues to be no prospective data to support a GI benefit of COX-2
      inhibitor plus a PPI over traditional NSAID plus a PPI in high-risk patients.

PMID- 16635219
TI  - H. pylori genotypes and cytokine gene polymorphisms influence the development of
      gastric intestinal metaplasia in a Chinese population.
AB  - BACKGROUND: Cytokine gene polymorphisms and Helicobacter pylori (HP) genotypes
      have been linked to gastric cancer development in Western countries. We
      determined the role of host cytokine polymorphisms and bacterial virulent factors
      in the development of gastric intestinal metaplasia (IM) in a Chinese population
      with a high background gastric cancer incidence. METHODS: Three hundred two HP
      infected noncancer individuals living in Shandong province of China with
      available DNA were studied. Polymorphisms in different loci of inflammatory
      cytokines Interleukin IL-1B, IL-1RN, Interleukin IL-8, IL-10, IL-18, tumor
      necrosis factor-A (TNF-A), and Transforming growth factor (TGF-B), were
      determined by allelic discriminating TaqMan polymerase chain reaction (PCR) or a
      variable number of tandem repeats. Presence of HP virulence factors in cagA,
      vacA, and babA2 were determined by PCR. Baseline gastric biopsies were assessed
      for the presence of IM. RESULTS: Among HP-infected subjects, carriers of the IL
      1B-511 T allele were associated with a modestly greater prevalence of IM
      (adjusted OR 2.0, 95% CI 1.0-3.7). There was no association between the presence
      of IM and polymorphisms in other inflammatory cytokines. Although most subjects
      from this region harbored the virulent HP strains, carriage of the vacA m1 strain
      was associated with a significantly higher prevalence of IM (adjusted OR 1.8, 1.1
      3.0). The presence of both host (IL-1B-511 T) and HP (vacA m1) genotypes further
      increased the risk of IM (OR 5.7, 2.0-16) when compared with individuals with the
      low-risk genotype. CONCLUSION: The carriage of proinflammatory IL-1B-511 and HP
      vacA m1 genotypes was associated with the development of gastric IM in the
      Chinese.

PMID- 16635220
TI  - Quality in colonoscopy: cecal intubation first, then what?
AB  - In 2002, the U.S. MultiSociety Task Force on Colorectal Cancer proposed multiple
      quality indicators for use in the continuous quality improvement (CQI) process
      for colonoscopy. The quality indicators were not prioritized for implementation
      in clinical practice. This editorial reviews evidence suggesting that after cecal
      intubation rates, two quality indicators should be the priorities for the CQI
      process for colonoscopy: (1) measurement of individual endoscopists' adenoma
      detection rates and (2) recommended intervals for postpolypectomy surveillance
      colonoscopy.

PMID- 16635221
TI  - Long-term outcome of biliary and duodenal stents in palliative treatment of
      patients with unresectable adenocarcinoma of the head of pancreas.
AB  - BACKGROUND: Life expectancy in patients with unresectable pancreatic cancer has
      improved by using new chemotherapeutic regimens. Biliary and digestive stenoses
      can be endoscopically treated in most cases. However, long-term efficacy of these
      stenting procedures remains unknown. AIM: To evaluate the incidence of biliary
      and duodenal stenoses as well as technical success and short- and long-term
      patency of endoscopically deployed stents in patients with unresectable
      pancreatic cancer. PATIENTS AND METHODS: All consecutive patients with
      unresectable cancer of the pancreatic head seen between January 1999 and
      September 2003 in our center were retrospectively studied. Patients with biliary
      and/or duodenal stenoses underwent endoscopic stent insertion as first intention
      therapy. Outcomes included technical and clinical success, stent patency, and
      survival. RESULTS: One hundred patients, median age 65 yr (32-85), with locally
      advanced (62%) or metastatic (38%) pancreatic cancer were studied. Eighty-three
      percent received at least one line of chemotherapy. The actuarial median survival
      was 11 months (0.7-29.3). Biliary and duodenal stenoses occurred in 81 and 25
      patients, respectively. A biliary stent was successfully placed in 74 patients
      (91%). When a self-expandable metallic stent was first introduced (N = 59), a
      single stent was sufficient in 41 patients (69%) (median duration of stent
      patency 7 months (0.4-21.1)). Duodenal stenting was successful in 24 patients
      (96%); among them, 96% required a single stent (median duration of stent patency
      6 months [0.5-15.7]). In the 23 patients who developed both biliary and duodenal
      stenoses, combined stenting was successful in 91% of cases. No major complication
      or death occurred related to endoscopic treatment. CONCLUSION: Endoscopic
      palliative treatment of both biliary and duodenal stenoses is safe and effective
      in the long term, including in patients with combined obstructions. Use of such
      palliative management is justified as repeat procedures are rarely required even
      in patients who have a long survival.

PMID- 16635222
TI  - Palliation in gastroduodenal obstruction.

PMID- 16635223
TI  - Watchful waiting after endoscopic removal of common bile duct stones: cheaper and
      better?
AB  - Drake et al. constructed a decision model to compare, in an older population, the
      costs and 2-yr survival rates of elective cholecystectomy versus expectant
      management after endoscopic removal of common bile duct (CBD) stones. The base
      case analysis indicated that the expectant management strategy dominated (less
      expensive and more effective) the elective surgery strategy. Sensitivity analysis
      suggested that the two strategies likely had equivalent effectiveness and that
      results were sensitive to the rate of recurrent biliary symptoms. Patient
      preferences for the different strategies (i.e., utilities) were not included in
      the model but are important to elicit and consider in clinical practice.

PMID- 16635224
TI  - On studying the connection between stress and IBD.
AB  - A number of investigators over the years have attempted to determine if a
      relationship exists between flares of inflammatory bowel disease (IBD) and
      stress. There are many complexities to addressing this issue, including
      determining the appropriate tools to measure stress, determining the appropriate
      measures of quantifying a disease flare and also determining the point at which
      the timing of the stress could be seen to be reasonably related to the onset of
      the flare. While advances have been made in understanding physiological responses
      to acute stress, it is unclear whether it is acute, chronic, or recurrent stress
      that might most impact on a chronic inflammatory disease. In the case of IBD, the
      disease itself poses a stress to the individual further clouding the issue.

PMID- 16635225
TI  - Randomized, double blind controlled trial of subcutaneous recombinant human
      interleukin-11 versus prednisolone in active Crohn's disease.
AB  - BACKGROUND: Interleukin-11 has shown benefit in animal inflammatory bowel disease
      models. Recently, recombinant human interleukin-11 (rhIL-11) has been observed to
      induce remission in a subset of patients with mild to moderate Crohn's disease
      (CD). The present study compared the efficacy of rhIL-11 versus prednisolone in
      remission induction in CD. METHODS: Patients with active CD were randomly
      assigned to receive either subcutaneous rhIL-11 (1 mg once weekly) and
      prednisolone placebo tablets, or active prednisolone (60 mg/day) and rhIL-11
      placebo, for 12 weeks. Prednisolone/placebo was tapered after week 1, and
      patients were assessed every second week. RESULTS: Fifty-one patients received
      medication: 13/27 (rhIL-11) and 17/24 (prednisolone) completed 12 weeks of
      treatment. Remission rates (intent to treat) for rhIL-11 versus prednisolone were
      4% versus 46% at week 4 (p < 0.001) and 19% versus 50% at week 6 (p < 0.05).
      Response to treatment (deltaCDAI > 100) was seen in 19% (rhIL-11) versus 63%
      (prednisolone) after 4 weeks (p < 0.002) and 37% versus 63% after 6 weeks (p =
      0.1). After 12 weeks of treatment, it was observed that 22% (rhIL-11) versus 21%
      (prednisolone) had remained in remission. Frequent side effects of rhIL-11
      included fever (n = 3), rash (4), arthralgia/arthritis (3), nausea/vomiting (3),
      and headache (6). CONCLUSION: rhIL-11 is well tolerated but significantly
      inferior when compared to prednisolone in short-term remission induction in
      patients with active CD. In this patient cohort, both treatments appeared to be
      poor in maintaining remission over a period of 3 months.

PMID- 16635226
TI  - Influence of motilin on gastric fundus tone and on meal-induced satiety in man:
      role of cholinergic pathways.
AB  - BACKGROUND: Motilin agonists are strong gastroprokinetics, but their impact on
      symptoms in delayed gastric emptying has been disappointing. It has been
      speculated that it is due to the contractile effect of motilin agonists on the
      proximal stomach, but the pathway involved and the symptomatic consequences have
      been incompletely elucidated. AIMS: To study whether motilin enhances proximal
      stomach tone and enhances meal-induced satiety and to evaluate whether this
      effect involves a cholinergic pathway. METHODS: A gastric barostat was used to
      study, in healthy subjects, the effect of motilin (300 ng/kg/30 min i.v.) or
      saline on fasting gastric fundus tone and on post-prandial relaxation. To
      evaluate the involvement of a cholinergic pathway, atropine (12 microg/kg/h) was
      administered intravenously simultaneously with or before and during motilin
      infusion in the fasting state. Finally, a satiety drinking test was performed in
      21 subjects twice after pretreatment with placebo or motilin and with placebo or
      atropine. RESULTS: Administration of motilin caused a significant increase of
      fasting fundus tone expressed as decrease of the mean balloon volume (324 +/- 60
      mL vs 213 +/- 62 mL, p < 0.05). Simultaneous administration of atropine and
      motilin did not generate a significant volume change (192 +/- 60 mL vs 181 +/- 83
      mL, NS), but pretreatment with atropine alone induced a relaxation, and when
      motilin was added this revealed an ongoing contraction (192 +/- 24 mL vs 136 +/-
      21 mL, p < or = 0.05). Motilin infusion also inhibited gastric accommodation (p <
      or = 0.05 vs placebo) and increased satiety during a satiety drinking test (p <
      or = 0.05 vs placebo). CONCLUSIONS: Administration of motilin causes a
      contraction of the proximal stomach in humans and increases meal-induced satiety.
      The effect of motilin is atropine-resistant and involves a direct muscular
      pathway or a non-cholinergic neural pathway.

PMID- 16635227
TI  - Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea
      and the treatment of Clostridium difficile disease.
AB  - CONTEXT: Antibiotic-associated diarrhea (AAD) is a common complication of most
      antibiotics and Clostridium difficile disease (CDD), which also is incited by
      antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis.
      The use of probiotics for these two related diseases remains controversial.
      OBJECTIVE: To compare the efficacy of probiotics for the prevention of AAD and
      the treatment of CDD based on the published randomized, controlled clinical
      trials. DATA SOURCES: PubMed, Medline, Google Scholar, NIH registry of clinical
      trials, metaRegister, and Cochrane Central Register of Controlled Trials were
      searched from 1977 to 2005, unrestricted by language. Secondary searches of
      reference lists, authors, reviews, commentaries, associated diseases, books, and
      meeting abstracts. STUDY SELECTION: Trials were included in which specific
      probiotics given to either prevent or treat the diseases of interest. Trials were
      required to be randomized, controlled, blinded efficacy trials in humans
      published in peer-reviewed journals. Trials that were excluded were pre-clinical,
      safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of
      unspecified probiotics, trials of prebiotics, not the disease being studied, or
      inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164
      subjects) met the inclusion and exclusion criteria. DATA EXTRACTION: One reviewer
      identified studies and abstracted data on sample size, population
      characteristics, treatments, and outcomes. DATA SYNTHESIS: From 25 randomized
      controlled trials (RCTs), probiotics significantly reduced the relative risk of
      AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials,
      probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p =
      0.005). CONCLUSION: A variety of different types of probiotics show promise as
      effective therapies for these two diseases. Using meta-analyses, three types of
      probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic
      mixtures) significantly reduced the development of antibiotic-associated
      diarrhea. Only S. boulardii was effective for CDD.

PMID- 16635228
TI  - Telomerase activation in human hepatocarcinogenesis.
AB  - Active telomerase is present in the majority of malignant human tumors, including
      most cases of hepatocellular carcinoma (HCC). Telomerase reverse transcriptase
      (hTERT), the catalytic subunit of telomerase, has been found to be expressed in
      HCCs, dysplastic (precancerous) nodules (DNs), and regenerative nodules arising
      in cirrhosis. In a study reported in this issue of the journal, hTERT mRNA levels
      were assessed by quantitative real-time RT-PCR in various nodular lesions
      dissected from liver specimens of patients with chronic hepatitis B. High levels
      of hTERT mRNA were present in HCCs, high-grade DNs, and occasional low-grade DNs,
      whereas low levels were found in normal livers, livers with chronic hepatitis B
      (with or without cirrhosis), large regenerative nodules, and most low-grade DNs.
      Therefore, quantitative assessment of hTERT mRNA may provide a useful adjunct to
      histopathologic evaluation of large hepatic nodules. Indeed, emerging data from
      gene expression analyses of DNs and HCCs suggest that hTERT can be included in
      sets of select genes that provide "molecular signatures" with utility in the
      diagnosis and management of nodular hepatic lesions. Most importantly, tackling
      the mechanisms of telomerase activation may provide new means of therapy for HCC
      and other cancers.

PMID- 16635229
TI  - Measuring the quality of endoscopy.

PMID- 16635230
TI  - Quality indicators for gastrointestinal endoscopic procedures: an introduction.

PMID- 16635231
TI  - Quality indicators for colonoscopy.

PMID- 16635232
TI  - Quality indicators for esophagogastroduodenoscopy.

PMID- 16635233
TI  - Quality indicators for endoscopic retrograde cholangiopancreatography.

PMID- 16635234
TI  - Quality indicators for endoscopic ultrasonography.

PMID- 16635235
TI  - Percutaneous endoscopic gastrostomy as a tool to assist pneumatic dilation in a
      difficult case of sigmoid esophagus.
AB  - We describe a case of a long-standing, untreated achalasia with a huge sigmoid
      esophagus in a 58-year-old Caucasian man who declined surgery. All means of
      classical endoscopic approach for pneumatic dilation, including the use of an
      overtube, were impossible because any attempt to propel the balloon dilator made
      the guide wire pull back out of the stomach because of the large loops and the
      tortuosity of the esophagus. For this reason, we used, for the first time, a
      combined approach of percutaneous gastrostomy and endoscopy in order to fix the
      guide wire at two points, achieving a pneumatic dilation in this way. A few
      months later, a significant improvement in the symptoms and nutritional status of
      the patient were observed.

PMID- 16635236
TI  - Bravo capsule pH monitoring.

PMID- 16635238
TI  - Colorectal cancer screening in HIV-infected patients 50 years of age and older:
      missed opportunities for prevention.

PMID- 16635240
TI  - Jejunal perforation for biliary stent dislocation.

PMID- 16635241
TI  - Optimization of timing of endoscopic variceal ligation of esophageal varices.

PMID- 16635242
TI  - Botulinum toxin and chronic anal fissure.

PMID- 16635243
TI  - Proceedings of the 1st ISN Special Neurochemistry Conference: Changes in neuronal
      gene expression and CNS drug responses. Avignon, France, 13-16 May 1004.

PMID- 16635244
TI  - The dopamine transporter proteome.
AB  - Dopamine (DA) uptake through the neuronal plasma membrane DA transporter (DAT) is
      essential for the maintenance of normal DA homeostasis in the brain. The DAT
      mediated re-uptake system limits not only the intensity but also the duration of
      DA actions at presynaptic and postsynaptic receptors. This protein is the primary
      target for cocaine and amphetamine, both highly addictive and major substances of
      abuse worldwide. DAT is also the molecular target for therapeutic agents used in
      the treatment of mental disorders, such as attention deficit hyperactivity
      disorder and depression. Given the role played by the DAT in regulation of DA
      neurotransmission and its contribution to the abuse potential of
      psychostimulants, it becomes not only important but also necessary to understand
      the functional regulation of this protein. To investigate the cellular and
      molecular mechanisms associated with DAT function and regulation, our laboratory
      and others have embarked on a systematic search for DAT protein-protein
      interactions. Recently, a growing number of proteins have been shown to interact
      with DAT. These novel interactions might be important in the assembly, targeting,
      trafficking and/or regulation of transporter function. In this review, I
      summarize the main findings obtained from the characterization of DAT-interacting
      proteins and discuss the functional implications of these novel interactions.
      Based on these new data, I propose to use the term DAT proteome to explain how
      interacting proteins regulate DAT function. These novel interactions might help
      define new mechanisms associated with the function of the transporter.

PMID- 16635245
TI  - Effect of ammonia on astrocytic glutamate uptake/release mechanisms.
AB  - Hyperammonemic disorders such as acute liver failure (ALF) or urea cycle
      enzymopathies are associated with hyperexcitability, seizures, brain edema and
      increased extracellular brain glutamate. Mechanisms responsible for increased
      glutamate content in the extracellular space of the brain include decreased
      uptake by perineuronal astrocytes and/or increased release from neurons and/or
      astrocytes. Exposure of astrocytes to millimolar concentrations of ammonia
      results in cell swelling, loss of expression of the glutamate transporters
      excitatory amino acid transporter (EAAT-1) and EAAT-2 and increased release of
      glutamate. Three distinct mechanisms are theoretically possible to explain
      ammonia-induced glutamate release from astrocytes namely: release due to
      swelling; reversal of glutamate transporters and due to Ca2+-dependent vesicular
      release. Recent identification of vesicular docking and fusion proteins in
      astrocytes together with glutamate-release (due to intracellular alkanization and
      mobilization of intracellular Ca2+-stores) studies implies that vesicular release
      is a predominant mechanism responsible for ammonia-induced release of glutamate
      from astrocytes.

PMID- 16635246
TI  - Molecular characterization and comparison of the components and multiprotein
      complexes in the postsynaptic proteome.
AB  - Characterization of the composition of the postsynaptic proteome (PSP) provides a
      framework for understanding the overall organization and function of the synapse
      in normal and pathological conditions. We have identified 698 proteins from the
      postsynaptic terminal of mouse CNS synapses using a series of purification
      strategies and analysis by liquid chromatography tandem mass spectrometry and
      large-scale immunoblotting. Some 620 proteins were found in purified postsynaptic
      densities (PSDs), nine in AMPA-receptor immuno-purifications, 100 in isolates
      using an antibody against the NMDA receptor subunit NR1, and 170 by peptide
      affinity purification of complexes with the C-terminus of NR2B. Together, the NR1
      and NR2B complexes contain 186 proteins, collectively referred to as membrane
      associated guanylate kinase-associated signalling complexes. We extracted data
      from six other synapse proteome experiments and combined these with our data to
      provide a consensus on the composition of the PSP. In total, 1124 proteins are
      present in the PSP, of which 466 were validated by their detection in two or more
      studies, forming what we have designated the Consensus PSD. These synapse
      proteome data sets offer a basis for future research in synaptic biology and will
      provide useful information in brain disease and mental disorder studies.

PMID- 16635247
TI  - Modulated splicing-associated gene expression in P19 cells expressing distinct
      acetylcholinesterase splice variants.
AB  - Alternative splicing configurations and acetylcholinesterase (AChE) gene
      expression are both modified in neurons under stress. However, it is unclear if
      these phenomena are functionally interrelated. Using a home-made spotted
      microarray focused on splicing-associated transcripts, we tested the effects of
      excess 3' splice variants of human AChE on splicing-related gene expression in
      semi-differentiated neuronal P19 cells. Of the tested transcripts, 17.3% and
      20.2% showed modified expression levels (log2 of the ratio<-0.3 or>0.3) in
      transfected P19 cells overexpressing the stress-inducible AChE-R variant or the
      synaptic AChE-S protein, respectively. Multiple transcripts encoding serine
      arginine rich (SR) and SR-related splicing regulators were suppressed in cells
      expressing either of these variants, whereas the gene groups including splicing
      related helicases and transcripts involved in apoptosis displayed variant
      specific changes. Our findings are compatible with the assumption that both
      neuronal overexpression and alternative splicing of pre-AChE mRNA may be causally
      involved in initiating global changes in neuronal alternative splicing, causing
      subsequent modifications in the expression patterns of numerous target genes.

PMID- 16635248
TI  - Gene expression is differentially regulated by neurotransmitters in embryonic
      neuronal cortical culture.
AB  - Neurotransmitters and their receptors have been involved in both proper brain
      development and neurodevelopmental disorders. The role that nicotinic receptors
      play in immature cortical neurons was initially investigated by gene profiling
      using Affymetrix DNA arrays. Both short (15 min) and prolonged (18 h) treatments
      with nicotine did not induce modification in gene expression, whereas a
      significant down-regulation of c-fos protein levels was observed after 18 h
      treatment. Conversely, a brief treatment with the glutamatergic agonist NMDA
      triggered up-regulation of immediate early genes and transcription factors, which
      remained unaffected by pre-treatment for 18 h with nicotine. Calcium imaging
      studies revealed that NMDA activated a sustained increase in intracellular
      calcium concentration in the majority of neurons, whereas nicotine evoked only a
      transient calcium increase in a smaller percentage of neurons, suggesting that
      the calcium signalling response was correlated with activation of gene
      expression. Nicotine effects on immature cortical neurons perhaps do not require
      gene regulation but may be still acting on signalling pathways.

PMID- 16635249
TI  - Effects of antidepressant treatment on gene expression profile in mouse brain:
      cell type-specific transcription profiling using laser microdissection and
      microarray analysis.
AB  - A gene expression study of mice treated with the tricyclic antidepressant
      amitriptyline was performed. To enable the detection of cell type-specific
      expression changes, laser-microdissected nucleus accumbens was analysed after 4
      and 28 days of treatment. After 4 days of treatment no significantly regulated
      genes could be detected in this study. In contrast, 95 genes exhibited different
      expression levels in animals treated for 28 days with amitrityline compared with
      sham animals. This observation reflects the long-term effects and adaptation
      processes observed in patients treated with this drug. Among the regulated genes
      are receptors belonging to the dopamine-dependent signalling cascade, ion
      channels (mainly voltage-dependent potassium and calcium channels) potentially
      involved in signalling cascades and neuropeptides. The results support the
      hypothesis that the therapeutic effect of this antidepressant is much more
      complex and not confined to a reuptake inhibition of neurotransmitters. Paradigms
      inducing only weak expression changes, which may be limited to certain cell types
      within the highly complex brain structure, can therefore be reliably investigated
      by applying a cell type-specific expression profiling technique based on laser
      microdissection and subsequent RNA amplification followed by DNA microarray
      analysis.

PMID- 16635250
TI  - Elucidating the murine brain transcriptional network in a segregating mouse
      population to identify core functional modules for obesity and diabetes.
AB  - Complex biological systems are best modeled as highly modular, fluid systems
      exhibiting a plasticity that allows them to adapt to a vast array of changing
      conditions. Here we highlight several novel network-based approaches to elucidate
      genetic networks underlying complex traits. These integrative genomic approaches
      combine large-scale genotypic and gene expression results in segregating mouse
      populations to reconstruct reliable genetic networks underlying complex traits
      such as disease or drug response. We apply these novel approaches to one of the
      most extensive surveys of gene expression studies ever undertaken in whole brain
      in a segregating mouse population. More than 23,000 genes were monitored in whole
      brain samples from more than 300 mice derived from an F2 intercross population
      and genotyped at over 1200 SNP markers uniformly spread over the entire genome.
      We explore the topological properties of the brain transcriptional network and
      highlight different approaches to inferring causal associations among genes by
      integrating genotypic and expression data. We demonstrate the utility of these
      approaches by identifying and experimentally validating brain gene expression
      traits predicted to respond to a strong expression quantitative trait locus
      (eQTL) for the pituitary tumor-transforming 1 gene (Pttg1) that coincides with
      the physical location of this gene (a cis eQTL). We identify core functional
      modules making up the brain transcriptional network in mice that are coherent for
      core biological processes associated with metabolic disease traits including
      obesity and diabetes.

PMID- 16635251
TI  - Intracellular domain of nicotinic acetylcholine receptor: the importance of being
      unfolded.
AB  - Bioinformatics methods with subsequent verification by experimental data were
      applied to the structural investigation of the intracellular loop of the delta
      subunit of the nicotinic acetylcholine receptor (nAChR). Three complementary
      methods were used: prediction of secondary structure elements, prediction of
      ordered/disordered protein regions and prediction of short functional binding
      motifs. The output of five different algorithms was used for the secondary
      structure construction. Most of the intracellular domain is predicted to be
      unfolded. The predictions correlate well with the experimental data of limited
      proteolysis and NMR performed on the mostly monomeric fraction of heterologously
      expressed Torpedo intracellular domain protein. Twelve functional binding motifs
      within the disordered regions of the nAChR intracellular domain are predicted.
      Identification of proteins that interact with the intracellular domain will
      provide a better understanding of protein-protein interactions involved in nAChR
      assembly, trafficking and clustering.

PMID- 16635252
TI  - Knocking-down the NMDAR1 subunit in a limited amount of neurons in the rat
      hippocampus impairs learning.
AB  - Amplicon vectors derived from herpes simplex virus type 1 were built to modify
      NMDA receptors by expressing antisense RNA for the essential NR1 subunit. Their
      ability to modify endogenous levels of NR1 was tested in cultures of rat embryo
      neocortical neurons. We studied behaviour and tested for expression in adult rats
      injected with those vectors into the dorsal hippocampus to find out which cells
      and how many appear involved in memory formation. Rats injected with vectors
      expressing NR1 antisense performed significantly worse than control rats in an
      inhibitory avoidance task. Immunohistochemistry was performed in brain slices
      from the same animals. The transduced cells represented 6-7% of pyramidal neurons
      in CA1, showing that a single gene knockdown of NR1 in a small number of neurons
      significantly impaired memory formation. Perhaps neurons undergoing synaptic
      plasticity are more susceptible to NR1 knockdown, and hence NMDAR are
      particularly required in those neurons undergoing synaptic plasticity during
      learning, or perhaps, and more likely, there is not a high level of redundancy in
      the hippocampal circuits involved, leading to the idea that a certain level of
      NR1 expression/availability appears necessary for memory formation in most of CA1
      pyramidal neurons.

PMID- 16635253
TI  - Transcriptional response to the neuroleptic-like compound Ampullosporin A in the
      rat ketamine model.
AB  - Psychotic disorders affecting up to 1% of the human population represent
      pathological changes to the metabolic homeostasis of the brain. Increasing
      evidence in the literature suggests complex biochemical and/or transcriptional
      alterations accompanying schizophrenia-like phenomena. Sub-chronic treatment with
      sub-anaesthetic doses of ketamine induces schizophrenia-related psychotic
      alterations that can be used as an animal model in the study of this disorder.
      Ampullosporin A belongs to a specific group of pore-forming fungal peptides,
      peptaibols. We focused on the analysis of molecular events occurring in the brain
      of ketamine-pre-treated rats after administration of Ampullosporin A with
      neuroleptic-like activity. The complex experimental approach allowed us to
      correlate the use of low molecular weight substances with a transcriptome
      fingerprint in the prefrontal cortex. We found 63 genes to be up-regulated and 22
      genes suppressed, with transthyretin, syndecan-1 and NeuroD1 showing the highest
      degree of up-regulation. Our results suggest the possibility that Ampullosporin A
      belongs to the group of neuroleptic-like compounds, inducing massive changes in
      neurotransmitter receptor composition, calcium signalling cascades and second
      messenger systems, and leading to the plastic reorganization of brain tissue,
      metabolic pathways and synapses.

PMID- 16635254
TI  - Semax, an analogue of adrenocorticotropin (4-10), binds specifically and
      increases levels of brain-derived neurotrophic factor protein in rat basal
      forebrain.
AB  - The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analogue of the N
      terminal fragment (4-10) of adrenocorticotropic hormone which, after intranasal
      application, has profound effects on learning and memory formation in rodents and
      humans, and also exerts marked neuroprotective effects. A clue to the molecular
      mechanism underlying this neurotropic action was recently given by the
      observation that Semax stimulates the synthesis of brain-derived neurotrophic
      factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured
      from rat basal forebrain. In the present study, we investigated whether Semax
      affects BDNF levels in rat basal forebrain upon intranasal application of the
      peptide. In addition, we examined whether cell membranes isolated from this brain
      region contained binding sites for Semax. The binding of tritium-labelled Semax
      was found to be time dependent, specific and reversible. Specific Semax binding
      required calcium ions and was characterized by a mean+/-SEM dissociation constant
      (KD) of 2.4+/-1.0 nm and a BMAX value of 33.5+/-7.9 fmol/mg protein. Sandwich
      immunoenzymatic analysis revealed that Semax applied intranasally at 50 and 250
      microg/kg bodyweight resulted in a rapid increase in BDNF levels after 3 h in the
      basal forebrain, but not in the cerebellum. These results point to the presence
      of specific binding sites for Semax in the rat basal forebrain. In addition,
      these findings indicate that the cognitive effects exerted by Semax might be
      associated, at least in part, with increased BDNF protein levels in this brain
      region.

PMID- 16635255
TI  - Identification of conserved modes of expression profiles during hippocampal
      development and neuronal differentiation in vitro.
AB  - Gene expression profiles can be regarded as sums of simpler modes, analogous to
      the modes of a vibrating violin string. Decomposition of temporal gene expression
      profiles into modes by singular value decomposition (SVD) was reported before,
      but the question as to what degree the SVD modes can be interpreted in terms of
      biology remains open. We report and compare the results of SVD of published
      datasets from hippocampal development, neuronal differentiation in vitro, and a
      control time-series hippocampal dataset. We demonstrate that the first SVD mode
      reflects the magnitude of expression, interpretable on the Affymetrix platform.
      In the datasets from gene profiling of hippocampal development and neuronal
      differentiation, the second mode reflects a monotonous change in expression,
      either up- or down-regulation, in the time course of experiment. We demonstrate
      that the top two SVD modes are conserved between datasets and therefore, likely
      reflect properties of the underlying system (gene expression in hippocampus)
      rather than of a particular experiment or dataset. Our results also indicate that
      the magnitude of expression, and the direction of change in expression during
      hippocampal development, are uncorrelated, suggesting that they are regulated by
      largely independent mechanisms.

PMID- 16635256
TI  - Increased expression of genes that control ionic homeostasis, second messenger
      signaling and metabolism in the carotid plaques from patients with symptomatic
      stroke.
AB  - The molecular mechanisms that render a carotid atherosclerotic plaque symptomatic
      have not yet been identified. Using an Affymetrix Human GeneChip set, we analyzed
      the gene expression patterns of 44 862 mRNA transcripts in surgically removed
      carotid artery plaques from six patients with symptomatic stroke and four non
      symptomatic patients. The age, body mass index and the degree of stenosis were
      similar in the two groups. Some 236 transcripts (approximately 0.5% of the total
      transcripts analyzed) were expressed more abundantly in the symptomatic than the
      asymptomatic group. Of these, 61 transcripts are those that participate in ionic
      homeostasis, signal transduction and metabolism. The other groups of transcripts
      up-regulated in the symptomatic plaques include oncogenes, growth factors, tumor
      markers, angiogenesis promoters, transcription factors, and RNA splicing and
      processing factors. This study indicates that the higher metabolic activity in
      some atherosclerotic plaques leads to their faster growth and precipitation of
      stroke symptoms. The implications of these findings are that both diagnosis and
      prevention of stroke symptoms may become possible at the genetic level.

PMID- 16635257
TI  - 12-O-tetradecanoyl-phorbol-13-acetate-dependent up-regulation of dopaminergic
      gene expression requires Ras and neurofibromin in human IMR-32 neuroblastoma.
AB  - The dopaminergic transcriptional programme is highly regulated during development
      and in the adult, in response to activation of membrane receptor signalling
      cascades. Gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme
      in dopamine synthesis, is known to be regulated by receptors that act through
      protein kinase C (PKC) or Ras signalling. To investigate possible interactions
      between these two pathways before they converge on Raf activation, we evaluated
      whether phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate, TPA)-dependent PKC
      activation required Ras for regulation of TH expression in IMR-32 cells. We found
      that long-term treatment with TPA, which induces down-regulation of PKC-alpha,
      led to induction of both protein and message levels of TH by autocrine factors.
      This was dependent on endogenous Ras, but independent of the transcription factor
      Nurr1. Moreover, this mechanism of action mimicked the effects of overexpression
      of the Ras-GAP domain of neurofibromin, GAP-related domain (GRD) I, which is part
      of the upstream mechanism for regulation of Ras activation and a PKC-alpha
      substrate. Overexpression of Ras also led to transcriptional and translational up
      regulation of TH, independent of Nurr1 induction, as well as distinct phenotypic
      changes consistent with cell hypertrophy and increased secretory activity shown
      by induction of expression of vesicular monoamine transporter 2 and synaptosomal
      associated protein-25. Most interestingly, overexpression of GRDI and down
      regulation of the endogenous GRDII neurofibromin led to significant increases in
      Nurr1 message, possibly reflecting a transcriptional hierarchy during
      development. Taken together, these studies suggest that PKC-alpha, neurofibromin
      and Ras are essential in regulation of TH gene expression in IMR-32 cells.

PMID- 16635258
TI  - Transcriptional disruptions in Down syndrome: a case study in the Ts1Cje mouse
      cerebellum during post-natal development.
AB  - To understand the aetiology and the phenotypic severity of Down syndrome, we
      searched for transcriptional signatures in a substructure of the brain
      (cerebellum) during post-natal development in a segmental trisomy 16 model, the
      Ts1Cje mouse. The goal of this study was to investigate the effects of trisomy on
      changes in gene expression across development time. The primary gene-dosage
      effect on triplicated genes (approximately 1.5) was observed at birth [post-natal
      day 0 (P0)], at P15 and P30. About 5% of the non-triplicated genes were
      significantly differentially expressed between trisomic and control cerebellum,
      while 25% of the transcriptome was modified during post-natal development of the
      cerebellum. Indeed, only 165, 171 and 115 genes were dysregulated in trisomic
      cerebellum at P0, P15 and P30, respectively. Surprisingly, there were only three
      genes dysregulated in development and in trisomic animals in a similar or
      opposite direction. These three genes (Dscr1, Son and Hmg14) were, quite
      unexpectedly, triplicated in the Ts1Cje model and should be candidate genes for
      understanding the aetiology of the phenotype observed in the cerebellum.

PMID- 16635259
TI  - Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA
      receptors in developing hippocampal neurones.
AB  - Drebrin is a major F-actin-binding protein in the brain. We have recently
      demonstrated that drebrin A (neurone-specific isoform) clusters at synapses and
      governs targeting of the post-synaptic density 95 protein to synapses during
      development. To determine the role of drebrin A on excitatory synapse formation,
      we analysed whether the suppression of drebrin A expression affects filopodia
      spine morphology and synaptic targeting of NMDA receptors in cultured hippocampal
      neurones. Suppression of developmentally programmed up-regulation of drebrin A by
      antisense treatment significantly decreased the density and width of filopodia
      spines. Immunocytochemistry showed that the antisense treatment did not attenuate
      synaptic clustering of NMDA receptors under conditions that permitted spontaneous
      activities but inhibited the accelerated targeting of NMDA receptors into
      synapses by its antagonist D-(-)-2-amino-5-phosphonopentanoic acid. These results
      indicate that drebrin A up-regulation plays a pivotal role in spine morphogenesis
      and activity-dependent synaptic targeting of NMDA receptors.

PMID- 16635260
TI  - Cell death and expression of heat-shock protein Hsc70 in the hyperthermic rat
      brain.
AB  - Stressful stimuli induce two distinct cellular reactions, the heat-shock (stress)
      response and programmed cell death. This study utilizes a dual procedure
      involving immunocytochemistry for heat-shock protein localization and the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling (TUNEL) assay for localization of cell death at the cellular level.
      Whole-body hyperthermia resulted in cell death in the adult rat thymus and testis
      with a robust signal seen in the testis. Distinct populations of constitutively
      expressed Hsc70-positive cells and TUNEL-positive cells were apparent. Cellular
      layers that exhibited high levels of Hsc70 were not triggered into cell death by
      the thermal stress. High expression of Hsc70 was observed in neuronal populations
      in the dentate gyrus, CA1 and CA2 region of the hippocampus and Purkinje neurons
      of the cerebellum. Hyperthermia-induced cell death was not observed in these
      neuronal cell types, suggesting that neuronal expression of constitutive Hsc70
      may play roles in preprotecting neurons from stressful stimuli.

PMID- 16635261
TI  - Thyroid cancer in Luxembourg: a national population-based data report (1983
      1999).
AB  - BACKGROUND: Twenty years after the nuclear accident in Chernobyl (Eastern
      Europe), there is still a controversial debate concerning a possible effect of
      the radioactive iodines, especially I-131, on the increase of thyroid carcinomas
      (TCs) in Western Europe. Time trends in incidence rates of TC in Luxembourg in
      comparison with other European countries and its descriptive epidemiology were
      investigated. METHODS: The population-based data of the national Morphologic
      Tumour Registry collecting new thyroid cancers diagnosed between 1983 and 1999 at
      a nation-wide level in the central division of pathology were reviewed and
      focused on incidence rates of TC. Data from 1990 to 1999 were used to evaluate
      the distribution by gender, age, histological type, tumour size and the outcome.
      RESULTS: Out of 310 new thyroid carcinomas diagnosed between 1990 and 1999, 304
      differentiated carcinomas (A: 80% papillary; B: 14.5% follicular; C: 3.5%
      medullary) and 6 anaplastic/undifferentiated TCs (D: 2%) were evaluated. The M/F
      ratio was 1:3.2, the mean age 48.3 years (range: 13-92). The overall age
      standardized (world population) incidence rates over the two 5-year periods 1990
      1994 and 1995-1999 increased from 7.4 per 100,000 to 10.1 per 100,000 in females,
      from 2.3 per 100,000 to 3.6 per 100,000 in males. Only 3 patients were children
      or adolescents (1%), the majority of the patients (50%) were between 45 and 69
      years of age. The percentage of microcarcinomas (<1 cm) was A: 46.4%, (115/248);
      B: 13.3%, (6/45); C: 27.3%, (3/11). The unexpected increase of TCs in 1997 was
      mainly due to the rise in the number of microcarcinomas. The observed 5-year
      survival rates for both genders were A: 96.0+/-2%; B: 88.9%; C: 90.9%; D: 0%.
      Prognosis was good in younger patients, worse in males and elderly, and extremely
      poor for undifferentiated TCs. CONCLUSION: The increasing incidence rates of TC,
      especially of the papillary type, seem mainly due to a rise in diagnosed
      microcarcinomas due to some extent to a change in histologic criteria and to more
      efficient diagnostic tools. This rise appears to be independent of the number of
      surgical treatments, the immigration rate, and the Chernobyl fallout as the
      incidence of TC in children remained stable.

PMID- 16635262
TI  - Improving health care quality for racial/ethnic minorities: a systematic review
      of the best evidence regarding provider and organization interventions.
AB  - BACKGROUND: Despite awareness of inequities in health care quality, little is
      known about strategies that could improve the quality of healthcare for ethnic
      minority populations. We conducted a systematic literature review and analysis to
      synthesize the findings of controlled studies evaluating interventions targeted
      at health care providers to improve health care quality or reduce disparities in
      care for racial/ethnic minorities. METHODS: We performed electronic and hand
      searches from 1980 through June 2003 to identify randomized controlled trials or
      concurrent controlled trials. Reviewers abstracted data from studies to determine
      study characteristics, results, and quality. We graded the strength of the
      evidence as excellent, good, fair or poor using predetermined criteria. The main
      outcome measures were evidence of effectiveness and cost of strategies to improve
      health care quality or reduce disparities in care for racial/ethnic minorities.
      RESULTS: Twenty-seven studies met criteria for review. Almost all (n = 26) took
      place in the primary care setting, and most (n = 19) focused on improving
      provision of preventive services. Only two studies were designed specifically to
      meet the needs of racial/ethnic minority patients. All 10 studies that used a
      provider reminder system for provision of standardized services (mostly
      preventive) reported favorable outcomes. The following quality improvement
      strategies demonstrated favorable results but were used in a small number of
      studies: bypassing the physician to offer preventive services directly to
      patients (2 of 2 studies favorable), provider education alone (2 of 2 studies
      favorable), use of a structured questionnaire to assess adolescent health
      behaviors (1 of 1 study favorable), and use of remote simultaneous translation (1
      of 1 study favorable). Interventions employing more than one main strategy were
      used in 9 studies with inconsistent results. There were limited data on the costs
      of these strategies, as only one study reported cost data. CONCLUSION: There are
      several promising strategies that may improve health care quality for
      racial/ethnic minorities, but a lack of studies specifically targeting disease
      areas and processes of care for which disparities have been previously
      documented. Further research and funding is needed to evaluate strategies
      designed to reduce disparities in health care quality for racial/ethnic
      minorities.

PMID- 16635263
TI  - Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol,
      retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV
      effects.
AB  - BACKGROUND: Current anti-AIDS therapeutic agents and treatment regimens can
      provide a dramatically improved quality of life for HIV-positive people, many of
      whom have no detectable viral load for prolonged periods of time. Despite this,
      curing AIDS remains an elusive goal, partially due to the occurrence of drug
      resistance. Since the development of resistance is linked to, among other things,
      fluctuating drug levels, our long-term goal has been to develop nanotechnology
      based drug delivery systems that can improve therapy by more precisely
      controlling drug concentrations in target cells. The theme of the current study
      is to investigate the value of combining AIDS drugs and modifiers of cellular
      uptake into macromolecular conjugates having novel pharmacological properties.
      RESULTS: Bioconjugates were prepared from different combinations of the approved
      drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier,
      poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities
      were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line,
      infected with HIV-1 strain Vbu 3, while parallel studies were performed in
      uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60
      times more potent than L-Tat9 while the addition of biotin resulted in a prodrug
      that was 2850 times more potent than L-Tat9. Flow cytometry and confocal
      microscopy studies suggest that variations in intracellular uptake and
      intracellular localization, as well as synergistic inhibitory effects of SQV and
      Tat peptides, contributed to the unexpected and substantial differences in
      antiviral activity. CONCLUSION: Our results demonstrate that highly potent
      nanoscale multi-drug conjugates with low non-specific toxicity can be produced by
      combining moieties with anti-HIV agents for different targets onto macromolecules
      having improved delivery properties.

PMID- 16635264
TI  - Improved method for predicting linear B-cell epitopes.
AB  - BACKGROUND: B-cell epitopes are the sites of molecules that are recognized by
      antibodies of the immune system. Knowledge of B-cell epitopes may be used in the
      design of vaccines and diagnostics tests. It is therefore of interest to develop
      improved methods for predicting B-cell epitopes. In this paper, we describe an
      improved method for predicting linear B-cell epitopes. RESULTS: In order to do
      this, three data sets of linear B-cell epitope annotated proteins were
      constructed. A data set was collected from the literature, another data set was
      extracted from the AntiJen database and a data sets of epitopes in the proteins
      of HIV was collected from the Los Alamos HIV database. An unbiased validation of
      the methods was made by testing on data sets on which they were neither trained
      nor optimized on. We have measured the performance in a non-parametric way by
      constructing ROC-curves. CONCLUSION: The best single method for predicting linear
      B-cell epitopes is the hidden Markov model. Combining the hidden Markov model
      with one of the best propensity scale methods, we obtained the BepiPred method.
      When tested on the validation data set this method performs significantly better
      than any of the other methods tested. The server and data sets are publicly
      available at http://www.cbs.dtu.dk/services/BepiPred.

PMID- 16635265
TI  - A steep decline of malaria morbidity and mortality trends in Eritrea between 2000
      and 2004: the effect of combination of control methods.
AB  - BACKGROUND: Malaria is a huge public health problem in Africa that is responsible
      for more than one million deaths annually. In line with the Roll Back Malaria
      initiative and the Abuja Declaration, Eritrea and other African countries have
      intensified their fight against malaria. This study examines the impact of
      Eritrea's Roll Back Malaria Programme: 2000-2004 and the effects and possible
      interactions between the public health interventions in use. METHODS: This study
      employed cross-sectional survey to collect data from households, community and
      health facilities on coverage and usage of Insecticide-Treated Nets (ITNs),
      Indoor Residual Spraying (IRS), larvicidal activities and malaria case
      management. Comparative data was obtained from a similar survey carried out in
      2001. Data from the Health Management Information System (HMIS) and reports of
      the annual assessments by the National Malaria Control Programme was used to
      assess impact. Time series model (ARIMA) was used to assess association. RESULTS:
      In the period 2000-2004, approximately 874,000 ITNs were distributed and 13,109
      health workers and community health agents were trained on malaria case
      management. In 2004, approximately 81% households owned at least one net, of
      which 73% were ITNs and 58.6% of children 0-5 years slept under a net. The
      proportion of malaria cases managed by community health agents rose from 50% in
      1999 to 78% in 2004. IRS coverage increased with the combined amount of DDT and
      Malathion used rising from 6,444 kg, in 2000 to 43,491 kg, in 2004, increasing
      the population protected from 117,017 to 259,420. Drug resistance necessitated
      regimen change to chloroquine plus sulfadoxine-pyrimethamine. During the period,
      there was a steep decline in malaria morbidity and case fatality by 84% and 40%
      respectively. Malaria morbidity was strongly correlated to the numbers of ITNs
      distributed (beta = -0.125, p < 0.005) and the amount (kg) of DDT and Malathion
      used for IRS (beta = -2.352, p < 0.05). The correlation between malaria case
      fatality and ITNs, IRS, population protected and annual rainfall was not
      statistically significant. CONCLUSION: Eritrea has within 5 years attained key
      Roll Back Malaria targets. ITNs and IRS contributed most to reducing malaria
      morbidity.

PMID- 16635266
TI  - Diabetes and urbanization in the Omani population: an analysis of national survey
      data.
AB  - BACKGROUND: The prevalence of type 2 diabetes in Oman is high and appears to be
      rising. Rising rates of diabetes and associated risk factors have been observed
      in populations undergoing epidemiological transition and urbanization. A previous
      study in Oman indicated that urban-dwellers were not significantly more likely to
      have diabetes. This study was undertaken to determine if a more accurate urban
      and rural categorization would reveal different findings. METHODS: This study
      included 7179 individuals aged 20 years or above who participated in a cross
      sectional interviewer-administered survey in Oman including blood and
      anthropomorphic tests. Multiple logistic regression analyses were conducted to
      analyze the factors associated with diabetes, first in the whole population and
      then stratified according to region. RESULTS: The prevalence of diabetes (fasting
      blood glucose > or = 7 mmol/l) in the capital region of Muscat was 17.7% compared
      to 10.5% in rural areas. The prevalence of self-reported diabetes was 4.3%. Urban
      residence was significantly associated with diabetes (adjusted odds ratio (OR) =
      1.7, 95% confidence interval (CI): 1.4-2.1), as was age (OR = 1.2, 95% CI: 1.1-
      1.2), obesity (abnormal waist circumference) (OR = 1.8, 95% CI: 1.5-2.1), and
      systolic blood pressure (SBP) 120-139 (OR = 1.4, 95% CI:1.04-1.8), SBP 140-159
      (OR = 1.9, 95% CI: 1.4-2.6), SBP > or = 160 (OR = 1.7, 95% CI: 1.2-2.5).
      Stratified analyses revealed higher education was associated with reduced
      likelihood of diabetes in rural areas (OR = 0.6, 95% CI: 0.4-0.9). CONCLUSION: A
      high prevalence of diabetes, obesity, hypertension and high cholesterol exist in
      the Omani population, particularly among urban-dwellers and older individuals. It
      is vital to continue monitoring chronic disease in Oman and to direct public
      health policy towards preventing an epidemic.

PMID- 16635267
TI  - Motion as a phenotype: the use of live-cell imaging and machine visual screening
      to characterize transcription-dependent chromosome dynamics.
AB  - BACKGROUND: Gene transcriptional activity is well correlated with intra-nuclear
      position, especially relative to the nuclear periphery, which is a region
      classically associated with gene silencing. Recently however, actively
      transcribed genes have also been found localized to the nuclear periphery in the
      yeast Saccharomyces cerevisiae. When genes are activated, they become associated
      with the nuclear pore complex (NPC) at the nuclear envelope. Furthermore,
      chromosomes are not static structures, but exhibit constrained diffusion in real
      time, live-cell studies of particular loci. The relationship of chromosome motion
      with transcriptional activation and active-gene recruitment to the nuclear
      periphery has not yet been investigated. RESULTS: We have generated a yeast
      strain that enables us to observe the motion of the galactose-inducible GAL gene
      locus relative to the nuclear periphery in real-time under transcriptionally
      active and repressed conditions. Using segmented geometric particle tracking, we
      show that the repressed GAL locus undergoes constrained diffusive movement, and
      that transcriptional induction with galactose is associated with an enrichment in
      cells with GAL loci that are both associated with the nuclear periphery and much
      more constrained in their movement. Furthermore, we report that the mRNA export
      factor Sac3 is involved in this galactose-induced enrichment of GAL loci at the
      nuclear periphery. In parallel, using a novel machine visual screening technique,
      we find that the motion of constrained GAL loci correlates with the motion of the
      cognate nuclei in galactose-induced cells. CONCLUSION: Transcriptional activation
      of the GAL genes is associated with their tethering and motion constraint at the
      nuclear periphery. We describe a model of gene recruitment to the nuclear
      periphery involving gene diffusion and the mRNA export factor Sac3 that can be
      used as a framework for further experimentation. In addition, we applied to the
      analysis of chromosome motion a machine visual screening approach that used
      unbiased visual data rather than segmented geometric data. This novel analytical
      approach will allow for high-throughput study of processes that can be monitored
      via alterations in chromosome motion and connectivity with the nuclear periphery.

PMID- 16635268
TI  - An alternative flow cytometry strategy for peripheral blood dendritic cell
      enumeration in the setting of repetitive GM-CSF dosing.
AB  - BACKGROUND: Enumeration of circulating peripheral blood dendritic cells (DCs) is
      complicated by the absence of a unique cell surface marker expressed on all DC
      subsets and by the use of various biological adjuvants to modulate the DC
      compartment, including granulocyte macrophage colony stimulating factor (GM-CSF).
      Common methods employ a cocktail of antibodies, typically including anti-CD14, to
      define a lineage negative, MHC class II positive, putative DC population.
      Reported flow cytometry protocols include highly variable gating strategies and
      DC identification criteria. Increasing appreciation of DC pleiomorphism, GM-CSF
      biology, and recognition of CD14 expression in some DC subsets led us to consider
      an alternative lineage cocktail to improve identification of the circulating DC
      pool. METHODS: Standard whole blood staining with appropriate fluorochrome
      conjugated antibodies to MHC class II and either standard CD14 containing, or an
      alternate CD66acde containing, lineage cocktail was performed on samples obtained
      from normal donors and breast cancer patients before and after administration of
      dose-dense, cytotoxic chemotherapy with daily GM-CSF hematopoetic growth factor
      support. Putative DCs were enumerated by standard flow cytometry. Data set
      differences were evaluated using two tailed Mann-Whitney or Wilcoxon signed rank
      tests. Cellular morphology was examined in cell-sorted populations from post GM
      CSF samples. RESULTS: Use of either antibody cocktail defined comparably sized
      lineage negative, MHC class II positive populations in normal donors and at
      baseline in cancer patients. However, selection of lineage negative subsets with
      increasing MHC class II expression levels yielded larger putative DC populations
      identified with the alternate cocktail. Both cocktails yielded highly
      reproducible data. Use of the alternate cocktail: 1) yielded a putative DC
      population, post GM-CSF that was more homogenous and consistent with DCs, 2)
      resulted in less data variation across gating strategies, and 3) resulted in more
      uniform and concordant longitudinal data, consistent with established GM-CSF
      biological activity. CONCLUSION: An alternative lineage negative cocktail
      substituting anti-CD66 antibody for anti-CD14 is a viable option for enumerating
      the circulating DC population, potentially more accurately defining the
      circulating DC pool by including CD14 positive immature DCs, and thus, may give
      more reliable data, particularly in the setting of sustained GM-CSF
      administration.

PMID- 16635269
TI  - Intraluminal instillation of urokinase and autologous plasma: a method to unblock
      occluded central venous ports.
AB  - BACKGROUND: Therapeutic use and effective function of recombinant urokinase (r
      UK) for occluded ports need the presence of plasminogen. METHODS: As a
      therapeutic proof of principle, we demonstrate that the use of r-UK and
      autologous plasma effectively reestablishes the function of occluded central
      venous ports (CVP) resistant to routine management of catheter occlusion. Five
      patients with occluded ports resistant to the routine management were treated.
      RESULTS: All patients were successfully treated with thrombolytic therapy using
      intraluminal instillation of r-UK and autologous plasma. CONCLUSION: Instillation
      of r-UK and autologous plasma is a safe and effective method for management of
      CVP occlusion.

PMID- 16635270
TI  - Early identification of intensive care unit-acquired infections with daily
      monitoring of C-reactive protein: a prospective observational study.
AB  - INTRODUCTION: Manifestations of sepsis are sensitive but are poorly specific of
      infection. Our aim was to assess the value of daily measurements of C-reactive
      protein (CRP), temperature and white cell count (WCC) in the early identification
      of intensive care unit (ICU)-acquired infections. METHODS: We undertook a
      prospective observational cohort study (14 month). All patients admitted for > or
      =72 hours (n = 181) were divided into an infected (n = 35) and a noninfected
      group (n = 28). Infected patients had a documented ICU-acquired infection and
      were not receiving antibiotics for at least 5 days before diagnosis. Noninfected
      patients never received antibiotics and were discharged alive. The progression of
      CRP, temperature and WCC from day -5 to day 0 (day of infection diagnosis or of
      ICU discharge) was analyzed. Patients were divided into four patterns of CRP
      course according to a cutoff value for infection diagnosis of 8.7 mg/dl: pattern
      A, day 0 CRP >8.7 mg/dl and, in the previous days, at least once below the
      cutoff; pattern B, CRP always >8.7 mg/dl; pattern C, day 0 CRP < or =8.7 mg/dl
      and, in the previous days, at least once above the cutoff; and pattern D, CRP
      always < or =8.7 mg/dl. RESULTS: CRP and the temperature time-course showed a
      significant increase in infected patients, whereas in noninfected it remained
      almost unchanged (P < 0.001 and P < 0.001, respectively). The area under the
      curve for the maximum daily CRP variation in infection prediction was 0.86 (95%
      confidence interval: 0.752-0.933). A maximum daily CRP variation >4.1 mg/dl was a
      good marker of infection prediction (sensitivity 92.1%, specificity 71.4%), and
      in combination with a CRP concentration >8.7 mg/dl the discriminative power
      increased even further (sensitivity 92.1%, specificity 82.1%). Infection was
      diagnosed in 92% and 90% of patients with patterns A and B, respectively, and in
      only two patients with patterns C and D (P < 0.001). CONCLUSION: Daily CRP
      monitoring and the recognition of the CRP pattern could be useful in the
      prediction of ICU-acquired infections. Patients presenting maximum daily CRP
      variation >4.1 mg/dl plus a CRP level >8.7 mg/dl had an 88% risk of infection.

PMID- 16635271
TI  - Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid
      arthritis in a German cohort: higher frequency of the risk allele in male
      compared to female patients.
AB  - The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a
      susceptibility locus for rheumatoid arthritis (RA). The study presented here
      describes the association of the PTPN22 1858T allele with RA in a German patient
      cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123
      patients, clinical and radiographic documentation over 6 years was available from
      the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an
      restriction fragment length polymorphism PCR-based genotyping assay. The odds
      ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95%
      confidence interval (CI) 1.85-3.58, p < 0.001), and 5.58 for homozygotes (95% CI
      1.85-16.79). The PTPN22 1858T allele was significantly associated not only with
      rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA,
      but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T
      allele was increased disproportionately in male patients (53.8% compared to 33.0%
      in female patients, p < 0.001), and the resulting odds ratio for male carriers
      was increased to 4.47 (95% CI 2.5-8.0, p < 0.001). Moreover, within the male
      patient population, the rare allele was significantly associated with the HLA
      DRB1 shared epitope (p = 0.01). No significant differences in disease activity or
      Larsen scores were detected. The results provide further evidence that the PTPN22
      1858T allele is associated with RA irrespective of autoantibody production. The
      increased frequency of the risk allele in male patients and its association with
      the shared epitope indicate that the genetic contribution to disease pathogenesis
      might be more prominent in men.

PMID- 16635272
TI  - Memorable medical mentors: XVI. Benjamin P. Watson (1880-1976).

PMID- 16635273
TI  - Sonographic findings in fetal viral infections: a systematic review.
AB  - Viral infections are a major cause of fetal morbidity and mortality.
      Transplacental transmission of the virus, even in subclinical maternal infection,
      may result in a severe congenital syndrome. Prenatal detection of viral infection
      is based on fetal sonographic findings and polymerase chain reaction to identify
      the specific infectious agent. Most affected fetuses appear sonographically
      normal, but serial scanning may reveal evolving findings. Common sonographic
      abnormalities, although nonspecific, may be indicative of fetal viral infections.
      These include growth restriction, ascites, hydrops, ventriculomegaly,
      intracranial calcifications, hydrocephaly, microcephaly, cardiac anomalies,
      hepatosplenomegaly, echogenic bowel, placentomegaly, and abnormal amniotic fluid
      volume. Some of the pathognomonic sonographic findings enable diagnosis of a
      specific congenital syndrome (eg, ventriculomegaly and intracranial and hepatic
      calcifications in cytomegalovirus, eye and cardiac anomalies in congenital
      rubella syndrome, limb contractures and cerebral anomalies in varicella zoster
      virus). When abnormalities are detected on ultrasound, a thorough fetal
      evaluation is recommended because of multiorgan involvement. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to recall that both
      clinical and subclinical maternal viral infections can cross the placenta,
      explain that there are specific sonographic findings along with laboratory
      findings to detect infectious agents, and state that when sonographic
      abnormalities are detected fetal viral infections need to be considered.

PMID- 16635274
TI  - Postpartum ovarian vein thrombosis: an update.
AB  - Ovarian vein thrombosis (OVT) is a rare complication of pregnancy. However,
      recognition and treatment is critical because a delay in diagnosis could lead to
      significant maternal morbidity. The diagnosis of OVT remains a challenge because
      there is no known profile of risk factors. Current controversies concern
      radiologic diagnosis, appropriate treatment strategies including antibiotics and
      anticoagulation, treatment duration, and testing for thrombophilias. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader should be able to explain that even
      though the occurrence of postpartum ovarian vein thrombosis (OVT) is rare the
      physician must consider it in a differential diagnosis in a patient with
      postdelivery fever unresponsive to antibiotics, state that missing the diagnosis
      can have devastating consequences, and recall that at times it is difficult to
      differentiate from septic thrombophlebitis.

PMID- 16635276
TI  - Colorectal cancer awareness month.

PMID- 16635275
TI  - Sickle cell anemia in the female patient.
AB  - Seventy-two thousand Americans are homozygous for the sickle cell gene and 2
      million are carriers. The gene offers protection against malaria but can be a
      cause of chronic pain and early death. Life expectancy is 48 years for females.
      Some people with sickle cell anemia live into their 60s and beyond. The purpose
      of this article is to review and summarize evidence from clinical, translational,
      and epidemiologic studies that have examined the clinically relevant aspects of
      sickle cell anemia as it relates to the female patient. Studies were identified
      through a MEDLINE search for articles in English between the years 1966 and 2005.
      References from identified reports were also used to identify additional
      articles. Women with sickle cell disease experience multiple complications. These
      complications can affect each and every organ system and are often worse in
      pregnant women. Progestins, hydroxyurea, and bone marrow transplant appear to
      ameliorate sickle cell anemia. Other therapies being evaluated include those that
      increase fetal hemoglobin concentration and prevent dehydration of the sickle red
      blood cells. More than one third of pregnancies in women with sickle syndromes
      terminate in abortion, stillbirth, or neonatal death. Recently, a number of genes
      modifying the clinical severity of sickle cell anemia have been identified.
      Sickle anemia is associated with immense suffering and multisystemic
      complications. In addition to the now-established therapy with hydroxyurea and
      bone marrow transplants, there are multiple investigational treatments that offer
      the hope of extending life expectancy while diminishing associated morbidities.
      Whether any of these new agents are safe in pregnancy has yet to be determined.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to
      summarize the multiple complications that women with sickle cell anemia (SCA)
      endure, explain that many of the complications worsen during pregnancy and
      increase the risk of an adverse pregnancy outcome, and state that there are
      treatment modalities that extend life and diminish morbidities.

PMID- 16635277
TI  - Highlights From: the 2006 American Society of Clinical Oncology Gastrointestinal
      Cancers Symposium San Francisco, CA, January 2006.

PMID- 16635278
TI  - Prognostic significance of increasing lymph node count in stage III colorectal
      cancer.

PMID- 16635279
TI  - Neoadjuvant treatment of unresectable liver metastases from colorectal cancer.
AB  - There has been increasing interest in the use of neoadjuvant treatment for
      downstaging and downsizing disease in patients with initially unresectable liver
      metastases from colorectal cancer with a view to potentially curative surgery.
      This has been increasingly feasible with the more active treatment combinations
      presently available based on oxaliplatin or irinotecan. This article reviews the
      evidence supporting the use of this treatment strategy and discusses the
      implications of advances in treatment in other metastatic disease settings for
      these patients and the issues of patient selection and prognostic factors.

PMID- 16635280
TI  - Ten-year results of preoperative radiation followed by sphincter preservation for
      rectal cancer: increased local failure rate in nonresponders.
AB  - BACKGROUND: The primary objective of this study was to determine the long-term
      outcome of sphincter preservation with preoperative radiation therapy (RT) and
      surgical resection in the treatment of distal rectal adenocarcinoma. PATIENTS AND
      METHODS: Between April 1988 and December 1996, 36 (cT2, n=9; cT3, n=27) patients
      with rectal adenocarcinoma were enrolled on a phase I/II trial of preoperative RT
      followed by surgical resection. All patients had distal tumors that were
      clinically judged to require an abdominoperineal resection and received
      preoperative RT (50.4 Gy) followed by surgery. The median follow-up was 94.5
      months (range, 4-187 months). RESULTS: Of the 35 patients in this study who
      underwent resection, 77% were able to undergo sphincter preservation after
      preoperative RT. The pathologic complete response rate for these patients was
      14%. The 10-year rates of overall survival and local failure for patients
      undergoing sphincter preservation were 54% and 21%, respectively. The 10-year
      local failure was 26% in patients with cT3 disease who underwent sphincter
      preservation. All local failures in this study occurred in patients with cT3
      disease undergoing sphincter preservation; however, none of the patients with cT3
      disease that was downstaged by preoperative RT experienced local failure. In
      contrast, 10-year local failure was 67% in the patients with cT3 disease that was
      not downstaged by RT. Sphincter function was good or excellent in 85% of patients
      at the time of last follow-up. CONCLUSION: This approach provides excellent long
      term results in all patients with cT2 disease and those with cT3 disease that is
      downstaged by RT. However, patients with cT3 disease that is not downstaged by RT
      have an increased risk of local failure. These data underscore the impact of
      tumor response to radiation on long-term oncologic outcome.

PMID- 16635281
TI  - Efficacy and safety of cetuximab/irinotecan in chemotherapy-refractory metastatic
      colorectal adenocarcinomas: a clinical practice setting, multicenter experience.
AB  - BACKGROUND: This study was designed to evaluate the efficacy and safety of
      irinotecan/cetuximab administered as third- or fourth-line therapy in a
      retrospective series of patients with metastatic colorectal cancer refractory to
      oxaliplatin and irinotecan. PATIENTS AND METHODS: Most patients (90%) had been
      previously treated with adjuvant 5-fluorouracil/leucovorin, and all had received
      oxaliplatin-based regimens before receiving irinotecan-based second-line
      treatment. Sixty patients with irinotecan-refractory colorectal cancer received a
      regimen comprising weekly irinotecan 120 mg/m2 as a 1-hour intravenous infusion
      and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2
      infused over 1 hour for the subsequent administrations. A single treatment cycle
      comprised 4 weekly infusions followed by 2 weeks of rest. RESULTS: According to
      an intent-to-treat analysis, a partial response was exhibited in 12 of 60
      enrolled patients (20%; 95% confidence interval, 11%-32%) with a median duration
      of 5.1 months (range, 3-7.4 months). The tumor growth control rate was 50% (95%
      confidence interval, 37%-63%). Objective responses did not correlate with
      performance status, number of sites of disease, and pretreatments or epidermal
      growth factor receptor status. The median progression-free survival was 3.1
      months (range, 1.2-9 months), whereas median overall survival was 6 months
      (range, 2-13 months). Both survival parameters correlated with performance status
      at the beginning of treatment. The main grade 3/4 toxicities were nausea (33%),
      diarrhea (27%), leukopenia (18%), asthenia (13%), and acne-like reaction (13%).
      CONCLUSION: Our data suggest that the weekly irinotecan/cetuximab regimen is
      feasible in an outpatient setting and tolerated by most patients. At present,
      combinations of chemotherapy with cetuximab are being evaluated in patients with
      earlier-stage disease in a number of ongoing studies.

PMID- 16635282
TI  - Multicenter phase II study of fixed sequences of capecitabine combined with
      oxaliplatin or irinotecan in patients with previously untreated metastatic
      colorectal cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the antitumor activity and
      toxicity of fixed sequences of capecitabine/oxaliplatin followed by
      capecitabine/irinotecan in patients with previously untreated metastatic
      colorectal cancer. PATIENTS AND METHODS: Adult patients with histologically
      confirmed, previously untreated, nonresectable, locally advanced or metastatic
      colorectal adenocarcinoma were enrolled in the study. Patients were treated as
      follows: capecitabine (1000 mg/m2 orally twice daily) on days 1-14 and
      oxaliplatin (130 mg/m2 2-hour intravenous infusion) on day 1, followed by
      capecitabine (1000 mg/m2 twice daily) on days 1-14 and irinotecan (240 mg/m2 1.5
      hour intravenous infusion) on day 1. Each combination was administered every 21
      days during 4 consecutive cycles followed by the alternating sequence to a
      maximum of 16 cycles. RESULTS: A total of 35 eligible patients have been included
      in this ongoing study. Response rate (complete responses plus partial responses)
      was 37.1%. With a median follow-up of 9.5 months, the median time to disease
      progression and overall survival were 7.4 months and 16.4 months, respectively.
      Treatment was well tolerated, with only 6% of the patients developing grade 3/4
      neurotoxicity. However, the low number of patients treated beyond 4 cycles limits
      the interpretation of the data. CONCLUSION: The preliminary results from this
      ongoing study suggest the feasibility of this strategy, which resulted in
      promising antitumor activity with less neurotoxicity.

PMID- 16635283
TI  - Southwest Oncology Group 0408: Phase II trial of neoadjuvant
      capecitabine/oxaliplatin/bevacizumab for resectable colorectal metastases in the
      liver.

PMID- 16635286
TI  - [Improving the clinical results of liver transplantation in China].

PMID- 16635287
TI  - [Chemosensitization of hepatocellular carcinoma using antisense
      oligonucleotides].

PMID- 16635288
TI  - [Adult-to-adult living donor liver transplantation for decompensated end-stage
      liver diseases].
AB  - OBJECTIVE: To summarize our clinical experience in adult-to-adult living donor
      liver transplantation (ALDLT). METHODS: Clinical data of 12 patients with ALDLT
      performed in our center from September 2000 to June 2005 were analyzed,
      retrospectively. RESULTS: Left lobe (segments II, III, IV, including the middle
      hepatic veins) transplantation was performed in 3 patients and right lobe
      (segments V, VI, VII, VIII, with or without the middle hepatic veins)
      transplantation was performed in 9 patients. Donors: There were no operative
      deaths. The median operative time was 6.20+/-1.40 hours and their blood loss
      ranged from 300 ml to 1200 ml. Postoperative complications included biliary
      fistula (1 donor) and wound fat liquefaction (1 donor). During a 6-12 months
      follow-up, no long-term complications were found. Recipients: The operating time
      ranged from 5 to 11 hours and their blood loss ranged from 800 to 7000 ml.
      Modified outflow reconstruction, microvascular reconstruction of the hepatic
      artery and duct-to-duct biliary reconstruction were done during the recipient
      operations. The median cold ischemia time was 1.90+/-0.50 hours. The median
      anhepatic phase of recipients was 1.63+/-0.43 hours. Graft/recipient weight ratio
      (GRWR) was (1.20+/-0.26)%. One recipient presented a postoperative complication
      of biliary fistula and another recipient died 1 month after the operation from
      serious infection. The other 11 recipients had long-term survivals. CONCLUSION:
      ALDLT is an effective treatment for decompensated end-stage liver disease
      patients and is relatively safe for the donors.

PMID- 16635289
TI  - [Clinicopathological analysis of biliary tract complications on post-liver
      transplantation patients].
AB  - OBJECTIVE: To analyze the pathohistological changes of the livers and the
      clinical features of patients with biliary tract complications after their
      orthotopic liver transplantations. METHODS: From Sept 1998 to June 2005 clinical
      and pathological data of 173 post-liver transplantation patients with biliary
      tract complications were analyzed. RESULTS: Biliary tract complications occurred
      within 3-2920 days after the transplantation operations. These complications
      occurred within 1-30 days, 31-90 days, 91-180 days, 180 days at rates of 49.71%,
      17.92%, 4.62%, 27.74% respectively. The complications were of inflammatory nature
      in 171 cases, (72.25%), and of obstructive nature in 164 cases (27.74%). The main
      pathological changes were epithelium degeneration of interlobular bile ducts,
      inflammatory cell infiltration in portal areas, proliferation of interlobular
      bile ducts, fibrosis in portal areas, cholestasis in small bile ducts and
      hepatocytes. CONCLUSION: Many of the biliary tract complications of post-liver
      transplantation in our cases were of inflammatory nature and they often occurred
      within 30 days after the surgery. Obstructive nature complications often occurred
      in 90 days after the surgery and the prognosis of these cases was much poorer.
      The pathological changes of live tissues shown in liver biopsies are important
      for prognostic evaluation, differential diagnosis and categorization of biliary
      tract complications.

PMID- 16635290
TI  - [Experimental study on tolerance time limits from warm ischemia to cold
      preservation of liver grafts].
AB  - OBJECTIVE: To investigate the tolerance time limits from warm ischemia to cold
      preservation of liver grafts. METHODS: Orthotopic liver transplantations (OLTs)
      were performed on Bama miniature swine. Morphological and functional changes of
      the liver grafts and biliary tracts after 10 minutes of warm ischemia followed by
      different durations of cold preservation and its reversibility were investigated.
      RESULTS: When the grafts were subjected to 10 minutes of warm ischemia followed
      by less than 16 hours of cold preservation, all animals could survive 1 week and
      there was no animal death from biliary necrosis. However, when the cold
      preservation time exceeded 16 hours, the incidence of biliary necrosis was
      significantly increased (P<0.05), and recipient death from bile leaks occurred.
      With further prolongation of the cold preservation time, primary graft
      nonfunction and intraoperative or early postoperative deaths occurred and the
      living animals all developed biliary necrosis. When compared with the less than
      16 hours cold preservation group, the morphological scores and apoptosis index of
      the epithelial cells of bile ducts in grafts after reperfusion were significantly
      elevated in the more than 16 hours cold preservation group (P<0.05) and the
      activity of Na+-K+-ATPase and Ca2+-ATPase of bile ducts in grafts were also
      significantly reduced (P<0.05). Liver function tests showed that the recoveries
      of AST, AST, GGT and ALP were quicker in the 16 hours cold preservation group
      then those over 16 hour preservation ones. Correlation analysis revealed that the
      incidence of biliary necrosis was significantly correlated with the morphological
      score (r = 0.972) and with the apoptosis index of the epithelial cells of bile
      ducts in grafts after reperfusion (r = 0.931) and also correlated negatively
      (P<0.01) with the activity of Na+-K+-ATPase (r = -0.973) and Ca2+-ATPase (r = 
      0.973). CONCLUSIONS: It is concluded that with 10 minutes of warm ischemia, cold
      preservation of the grafts should not be longer than 16 hours in order to avoid
      early biliary necrosis, and the corresponding tolerance time limit of the livers
      to the cold preservation was less than 20 hours.

PMID- 16635291
TI  - [Liver transplantation for treating hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the role of orthotopic liver transplantation (OLT) in
      treating hepatocellular carcinoma (HCC). METHODS: Data of 92 consecutive
      orthotopic liver transplantations (OLTs) performed during January 1999 and
      February 2005 at our institution were analyzed. RESULTS: Of the 92 recipients, 8
      HCC patients were stage I, 13 were stage II, 12 stage III and 59 stage IV (UICC
      TNM staging system). Overall 1-, 2-, 3-, 5-year patient survival rates were
      65.3%, 27.0%, 20.0%, and 6.9%, respectively. When OLT indications were
      considered, best recipients survival was obtained in stage I patients (100.0%,
      100.0%, 66.7%, and 50.0% at 1, 2, 3, and 5 years, respectively) and stage II
      patients (85.7%, 66.7%, and 66.7% at 1, 2 and 3 years, respectively). Whereas, 1,
      2, 3 and 5-year recipients survival rates were 50.0%, 0, 0, 0 in stage III
      patients, and 58.1%, 20.0%, 13.0% and 5.0% in stage IV patients. CONCLUSIONS: The
      prognosis of different stages of HCC patients who underwent OLT was significantly
      different. The OLT recipients with HCC should be strictly selected. Long-term
      recipient survival could be obtained in stage I and stage II patients.

PMID- 16635292
TI  - [Monitoring portal vein complications following liver transplantation by color
      Doppler flow imaging].
AB  - OBJECTIVES: To explore the diagnostic value of color Doppler flow imaging (CDFI)
      in monitoring portal vein complications (PVC) following orthotopic liver
      transplantation (OLT). METHODS: Five hundred and four patients received OLT and
      had CDFI examinations before and after their transplantations. CDFI monitoring
      parameters before the operation included portal vein diameter, blood flow
      velocity and the presence of thrombi within the portal vein. Monitoring
      parameters after the operation included portal vein diameters of donor and
      receiver sides, and the diameter of the mouth of anastomosis, inner side of blood
      vessel echo, the direction of blood flow and its speed. RESULTS: Of the 504
      patients examined, the median velocity of the portal blood flow was 46.27 cm/s
      (range: 15.8 to 110.8) on the day of the operation. The blood flow speed of 358
      cases (71.03%) was higher than 40 cm/s. Of the 358 patients, 347 (68.85%) had a
      blood flow speed lower than 40 cm/s one month after the operation. Sixty-four
      patients (12.70%) showed hepatofugal blood flow once, and only one case had a
      total hepatofugal blood flow. Thirteen patients (2.58%) had portal vein
      complications, including 4 cases with portal vein thrombosis and 9 with portal
      vein stenosis. CONCLUSION: Not all abnormal portal vein blood flow signals will
      lead to complications. It is worthwhile to monitor the portal blood flows. CDFI
      plays an important role in the diagnosis of portal vein complications after
      orthotopic liver transplantation.

PMID- 16635293
TI  - [Lamivudine administration prevents fulminant hepatic failure in patients with
      severe chronic hepatitis B].
AB  - OBJECTIVES: To study the effect of using lamivudine to prevent fulminant hepatic
      failure (FHF) in patients with chronic hepatitis B. METHODS: 164 patients were
      randomly put into a conventional supporting treatment control group and a
      lamivudine treatment group. In the latter, 82 patients were given lamivudine
      orally at a dose of 100 mg every day besides the support care which was also
      given to the control group. RESULTS: The rate of deterioration to chronic severe
      hepatitis in the lamivudine treatment group was significantly lower than that of
      the control group (23.2% vs. 46.3%, P < 0.01). 52.6% (20/38) with chronic severe
      hepatitis in the control group died. Only 26.3% (5/19) in the lamivudine
      treatment group succumbed to terminal liver disease (P < 0.01). There was a
      significant difference between the two groups in regards to the complication
      incidence of gastrointestinal bleeding, infections, hepatic coma, and kidney
      failure (P < 0.05). In addition, the recovery of liver function and liver
      fibrosis, and the rates of HBeAg loss and seroconversion in the lamivudine
      treatment group were better than those in the control group. Furthermore, the
      serum HBV DNA levels decreased more rapidly and continued to be substantially
      suppressed in the lamivudine treatment group. CONCLUSIONS: Our results suggest
      that lamivudine administration with improved support care not only is likely to
      prevent chronic severe hepatitis occurrence in patients with chronic viral
      hepatitis B of a severe degree, but also shows some efficacy in preventing FHF.

PMID- 16635294
TI  - [The role of peripheral blood mononuclear cells (PBMC) of HBV-infected mothers in
      the intrauterine infection of their fetuses].
AB  - OBJECTIVE: To study the role of the HBV-infected mothers' PBMC in intrauterine
      transmission of HBV to their fetuses. METHODS: Thirty pregnant women with serum
      HBV DNA negative and PBMC HBV DNA positive and their newborns were used as the
      study group. Ten pregnant women with serum HBV negative and their infants served
      as the control group. HBV DNA in serum and in PBMC was detected using nested
      polymerase chain reaction (n-PCR). The mothers' PBMC in newborns' peripheral
      blood was examined using heminested-PCR. RESULTS: Four newborns were serum HBV
      DNA positive and 8 newborns were HBV DNA positive in PBMC in the study group.
      Among them, 2 newborns were HBV DNA positive in both serum and PBMC, 6 cases were
      positive in PBMC only, and 2 cases were positive in serum only. Five mothers had
      the GSTM1 gene; and it was not detected in 3 newborns. Among the 8 newborns with
      HBV DNA positive in PBMC, 3 did not have the GSTM1 gene, at the same time their
      mothers possessed the GSTM1 gene. Mothers' PBMC were detected in all of these
      three newborns' peripheral blood. HBV DNA in serum and in PBMC of the control
      group infants were all negative. CONCLUSION: HBV-infected PBMC of the mother may
      serve as a vector in HBV intrauterine infection.

PMID- 16635295
TI  - [Construction and expression of EGFP controlled HBV promoters in eukaryotic
      cells].
AB  - OBJECTIVE: To construct four expression vectors carrying enhanced green
      fluorescent protein (EGFP) gene under the control of different HBV promoters, and
      to detect and analyze their expressions in hepatoma cell lines. METHODS: Four HBV
      promoters were amplified using PCR, and they were inserted into the T-vector and
      identified using restriction enzymes and sequencing, then cloned into the
      expression vector pEGFP-1. The four recombinant plasmids were transfected into
      human hepatoma cell line HepG2 by lipofectamine2000, and the positive cell clones
      were detected using fluorescence microscopy. RESULTS: All target fragments were
      separately obtained and successfully cloned into the expression vector. The
      expressions of EGFP under the control of the four promoters were detected. The
      expressions of EGFP controlled by different promoters had some differences.
      CONCLUSIONS: Reporter gene EGFP under the control of four HBV promoters can be
      specifically expressed in hepatoma cell line HepG2, and different promoters give
      different results; this may provide another option in gene therapy of liver
      diseases.

PMID- 16635296
TI  - [A preliminary study on anti-liver cancer immunity of the virus-like particulate
      peptide-nucleic acid vaccine].
AB  - OBJECTIVES: To construct a novel virus-like particulate peptide-nucleic acid
      vaccine (VPNV) of human telomerase reverse transcriptase (hTERT), and to study
      its anti-liver cancer immunity. METHODS: A cationic antigenic peptide was
      synthesized and purified, and then human granulocyte macrophage colony
      stimulating factor (hGM-CSF) and TERT gene were cloned into the eukaryotic
      expression vector pTCAE. The peptide was combined with the nucleic acid vaccine
      to make a VPNV, which was transfected into eukaryotic cell COS-7. The
      immunogenicity of hGM-CSF and hTERT were detected using ELISA and Western blot.
      The efficacy of VPNV for inducing antigen specific CTL response was determined
      using the lactate dehydrogenase release method. RESULTS: VPNV was verified
      capable to trigger specific CTL responses and has shown a specific cytolytic
      activity to liver cancer cell HepG2. CONCLUSION: A VPNV which can stimulate
      antigen specific CTL response was successfully constructed. This paves the way
      for our further investigation of anti-liver cancer immunity in mice.

PMID- 16635297
TI  - [Reconstructing the JAK/STATs signal pathway restored the anti-proliferative
      response of MHCC97 on interferon alpha].
AB  - OBJECTIVE: To elucidate the roles of JAK/STATs signal pathway on anti
      proliferative effects induced by IFN-alpha in MHCC97. METHODS: An IRF9 expression
      vector was transfected into MHCC97 with Dosper. The expression of IRF9, cycle
      regulating proteins and the forming of ISGF3 complex were detected using Western
      blot and EMSA, respectively. Cell proliferation and distribution were monitored
      using MTT and flow cytometry. RESULTS: High expression of IRF9 restored the anti
      proliferative response of MHCC97 on IFN-alpha treatment and delayed the cell
      transition from S phase to G2 phase induced by IFN-alpha. CONCLUSION: The
      integrity and functions of JAK/STATs signal pathway played an important role in
      mediating the anti-proliferative effects of IFN-alpha in MHCC97.

PMID- 16635298
TI  - [Expression and significance of hypoxia inducible factor-1 alpha in
      hepatocellular carcinoma tissues].
AB  - OBJECTIVES: To investigate the expression and significance of HIF1 alpha in
      hepatocellular carcinoma (HCC) tissues and in hepatoma carcinoma cell line HepG2.
      METHODS: The expression of the HIF1 alpha mRNA and protein were detected with
      immunohistochemistry (IHC), Western blot and RT-PCR techniques in HCC, normal
      liver tissues and HepG2. Their relationship with the pathological characteristics
      of the HCC was also analyzed. RESULTS: HIF1 alpha protein was obviously expressed
      in HCC. The positive rate of HIF1 alpha protein in HCC tissues was 76.4% and was
      higher than that in normal hepatic tissues. The expression of HIF1 alpha had a
      correlation to the differentiation degree of HCC tissues and intrahepatic and
      extrahepatic metastases (P<0.05), but there was no correlation to the existence
      of portal vein tumor emboli, the status of HBsAg and the prognosis (P<0.05). The
      results of Western blot and RT-PCR were similar to the results of IHC. The
      positive rate of HIF1 alpha in HepG2 was 93.6%. The levels of HIF1 alpha protein
      and mRNA began to increase after being treated two hours with hypoxia or with
      CoCl(2) (150 micromol/L). CONCLUSIONS: HIF1 alpha protein is obviously expressed
      in HCC and it is mainly affected by hypoxia. The expression of HIF1 alpha is
      related to the differentiation of the HCC and its intrahepatic and extrahepatic
      metastases but has no correlation to the existence of portal vein tumor emboli,
      the status of HBsAg and the prognosis.

PMID- 16635299
TI  - [Effect of hydroxycamptothecin on apoptosis-inducing factor (AIF) expression and
      on AIF translocation in human hepatocellular cancer cell SMMC-7721].
AB  - OBJECTIVE: To study the effect of hydroxycamptothecin (HCPT) on apoptosis
      inducing factor (AIF) expression and AIF translocation from mitochondria to the
      nucleus in human hepatocellular cancer cell SMMC-7721 during apoptosis. METHODS:
      After treatment with 80 mg/ml of HCPT, the cancer cells were stained with A0/EB
      to monitor their apoptosis. Their mitochondria was examined with
      electronmicroscopy and the AIF expression of the cells was tested by RT-PCR and
      Western blot. The translocation of AIF from mitochondria to the nucleus during
      apoptosis was analyzed by confocal microscopy. RESULTS: SMMC-7721 cells treated
      with HCPT showed chromatin condensation, nuclear fragmentation and mitochondria
      swelling. The mRNA and protein expression of AIF in treated and untreated SMMC
      7721 cells were not significantly different. However, cells treated with 80 mg/ml
      HCPT for 6 h or 12 h showed massive translocation of AIF into the nuclei.
      CONCLUSION: These results show the important role the mitochondrial pathway of
      apoptosis plays in HCPT-induced tumor cell death, at least in SMMC-7721 cells.

PMID- 16635300
TI  - [Liver transplantation for end-stage alcoholic liver diseases].

PMID- 16635301
TI  - [A clinical analysis of liver disease patients with abnormal glucose metabolism].
AB  - OBJECTIVE: To study the clinical features of liver disease patients with abnormal
      glucose metabolism. METHODS: Liver functions and levels of FPG, PPG, FINS, PINS,
      FCP, and PCP in 91 chronic hepatitis B patients with abnormal glucose metabolism
      (62 had liver cirrhosis) were analyzed. RESULTS: (1) The incidence of hepatogenic
      impaired glucose tolerance (IGT) and of diabetes mellitus (DM) in hepatitis B
      patients with liver cirrhosis (20.53%; 24.11%) were higher than those without
      cirrhosis (3.82%; 1.64%; P<0.05, P<0.01). (2) There were no diabetic symptoms
      among any of the hepatogenic IGT and DM patients. 12 of 19 chronic hepatitis B
      patients with primary DM and 6 of 12 hepatitis B associated liver cirrhosis
      patients with primary DM had diabetic symptoms. (3) The levels of FPG and PPG in
      chronic hepatitis B patients with hepatogenic IGT and DM were lower than those in
      the patients with primary DM (P<0.05), but the levels of PINS and PCP in chronic
      hepatitis B patients with hepatogenic IGT and DM were higher than those in the
      patients with primary DM (P<0.05). (4) There were no differences in the levels of
      FPG and PPG between the hepatitis B associated liver cirrhosis patients with
      hepatogenic DM and those with primary DM (P<0.05). The levels of FINS, PINS, FCP,
      and PCP were higher in the hepatitis B associated liver cirrhosis patients with
      hepatogenic DM than those in the hepatitis B associated liver cirrhosis patients
      with primary DM (P<0.05). The levels of FPG and PPG in the hepatogenic DM
      patients were higher than those in the hepatogenic IGT patients (P<0.05), but
      their levels of FINS, PINS, FCP and PCP were lower than those in the hepatogenic
      IGT patients (P<0.05, P<0.01). CONCLUSION: Hepatogenic IGT and DM are always
      secondary in severe liver cirrhosis patients, who always showed no diabetic
      symptoms. The chronic hepatitis B patients with hepatogenic DM had increased
      insulin secretion, while the hepatitis B associated liver cirrhosis patients with
      hepatogenic DM had decreased insulin secretion.

PMID- 16635302
TI  - [Treatment of portal vein thrombus in liver transplantation].

PMID- 16635303
TI  - [Prophylaxis of HBV reinfection by immune therapy after liver transplantation].

PMID- 16635304
TI  - [Transarterial administration of GRGDSP combined with chemoembolization for
      treating hepatic carcinoma in rats].

PMID- 16635305
TI  - [Expression of heparanase and b-FGF in HCC and their relationships with
      microvascular density].

PMID- 16635306
TI  - [The value of CA19-9 in diagnosing hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma].

PMID- 16635307
TI  - [A study of AFP and ALB expression in human mesenchymal stem cells induced by
      hepatopathy patient serum].

PMID- 16635308
TI  - [Screening differentially expressed genes of asymptomatic HBV carriers by
      suppression subtracted hybridization].

PMID- 16635309
TI  - [Effects of extracts of Rhizoma curcumae on angiotensin II and its type 1
      receptor expression in rat liver fibrosis induced by CCl4].

PMID- 16635310
TI  - [Prevention of hepatic failure induced by BCG and lipopolysaccharide in mice
      using mycophenolate mofetil].

PMID- 16635311
TI  - [Stereotactic radiotherapy for hepatocellular carcinoma with portal tumor
      thrombi].

PMID- 16635312
TI  - [The use of flow cytometry in detecting CMV-PP65 antigenemia for the diagnosis of
      CMV hepatitis].

PMID- 16635313
TI  - [Association of the CD28 gene promoter-372G/A polymorphism with chronic hepatitis
      B].

PMID- 16635314
TI  - [Primary malignant fibrous histiocytoma of the liver: an analysis of 3 cases].

PMID- 16635315
TI  - [Relationship between abnormal expression of heat shock protein 90 and malignant
      transformation of hepatocytes].

PMID- 16635317
TI  - [Establish harmonious medical culture by enhanced humanistic education].

PMID- 16635316
TI  - [Progress in silencing HBV gene expression by RNAi technologies].

PMID- 16635318
TI  - [Emphasis on the study on premature rupture of the membranes].

PMID- 16635319
TI  - [Study on the relationship between copper, lysyl oxidase and premature rupture of
      membranes].
AB  - OBJECTIVE: To determine the relationships between maternal serum copper, amniotic
      copper, lysyl oxidase (LOX) and collagen III in pregnant women with premature
      rupture of membranes (PROM) and without PROM. METHODS: One hundred women with
      PROM were enrolled in this study, and divided into 37-42 weeks, 34-36(+6) weeks
      and 28-33(+6) weeks according to gestational age. One hundred non-PROM
      pregnancies matching the same gestational ages were recruited as control group.
      Copper of maternal serum and amnion in two groups were compared by FAAS method.
      Amniotic LOX was analyzed by fluorometry. Amniotic collagen III was detected by
      immunohistochemical method and computer image analysis system (absorbance, A).
      Linear correlation analysis was used to explore the relationships between
      maternal serum copper, amniotic copper, LOX and collagen III. RESULTS: (1) For 37
      42 weeks pregnant women, serum copper was correlated positively with amniotic
      copper in two groups, r = 0.82 (P < 0.001), but for other parameters, the serum
      and amniotic levels had no correlations. (2) For 34-36(+6) and 28 - 33(+6) weeks
      pregnant women, there were positive correlations between serum copper, amniotic
      copper, LOX and collagen III in two groups (P < 0.01). (3) For 37-42 weeks
      pregnant women, serum copper and amniotic copper had no difference between two
      groups (P > 0.05), but amniotic LOX and collagen III decreased significantly
      compared with controls, being [(0.53 +/- 0.10) microg/g vs (0.75 +/- 0.10)
      microg/g, P < 0.01], (0.36 +/- 0.01 vs 0.37 +/- 0.01, P < 0.05) respectively. (4)
      For 34 - 36(+6) weeks pregnant women, serum copper, amniotic copper, LOX and
      collagen III reduced obviously between two groups (P < 0.01), being respectively
      [(115.23 +/- 9.56) mg/L vs (139.03 +/- 10.59) mg/L], [(0.21 +/- 0.04) microg/mg
      vs (0.29 +/- 0.04) microg/mg], [(0.54 +/- 0.10) microg/g vs (0.70 +/- 0.13)
      microg/g], and (0.36 +/- 0.01 vs 0.37 +/- 0.01). (5) For 28-33(+6) weeks pregnant
      women, serum copper, amniotic copper, LOX and collagen III also reduced obviously
      between two groups (P < 0.01), [(120.31 +/- 8.04) microg/L vs (136.40 +/- 8.21)
      microg/L], [(0.21 +/- 0.04) microg/mg vs (0.26 +/- 0.03) microg/mg], [(0.62 +/-
      0.09) microg/g vs (0.72 +/- 0.09) microg/g], and (0.35 +/- 0.01 vs 0.38 +/-
      0.01). CONCLUSION: For term pregnant women, the decreases of amniotic LOX and
      collagen III in PROM group are not affected by serum copper, perhaps by excessive
      degeneration of amnion; for non-term pregnant women, the decreases of serum
      copper, amniotic copper, LOX and collagen III are correlated directly with PROM.

PMID- 16635320
TI  - [Experimental study of repairing damaged human amniotic epithelial cells with
      formulated fibrin clot and cell growth factor].
AB  - OBJECTIVE: To investigate whether damaged human amniotic epithelial cells (HAEC)
      could be repaired on the matrix of formulated fibrin clot in vitro and the
      effects of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF)
      and transforming growth factor beta(1) (TGF-beta(1)) on the proliferation of
      HAEC. METHODS: Ring drill was used to drill the HAEC layer on culture sheets to
      make quantified models of damaged HAEC, on which the lacks were then covered with
      fibrin clot. Subsequently, EGF (EGF group), bFGF (bFGF group) and TGF-beta(1)
      (TGF-beta(1) group) of different concentration were added into the sheets
      respectively. After the predesigned culturing time, the growing and transiting
      conditions of HAEC were observed under inverted microscope after Giemsa stain.
      Also, the proliferating conditions of HAEC were detected by using 5
      bromodeoxyuridine (BrdU). RESULTS: In all groups, HAEC could transit toward
      damaged area on fibrin clot and grow there. Higher transiting speed and larger
      cell numbers were observed in the EGF and bFGF groups followed by the control
      group, while the TGF-beta(1) group showed the relatively poorer results.
      Proliferating rates of HAEC were 17.8%, 28.0%, 35.3%, 51.6%, 34.1%, 34.2% and
      26.0% respectively by EGF of different cultured concentration (1.0 ng/ml, 5.0
      ng/ml, 10.0 ng/ml, 20.0 ng/ml, 40.0 ng/ml, 80.0 ng/ml and 160.0 ng/ml).
      Proliferating rates of HAEC were 18.0%, 35.7%, 43.0%, 52.7%, 67.4%, 43.6% and
      30.5% respectively by bFGF of different cultured concentration (1.0 ng/ml, 5.0
      ng/ml, 10.0 ng/ml, 20.0 ng/ml, 40.0 ng/ml, 80.0 ng/ml and 160.0 ng/ml). Compared
      with the control group, EGF groups (EGF concentration ranging from 10 ng/ml to 80
      ng/ml) and bFGF groups (bFGF concentration ranging from 5 ng/ml to 80 ng/ml)
      showed better proliferating effects of HAEC (P < 0.05), especially the 20 ng/ml
      EGF group and 40 ng/ml bFGF group had the best proliferating results among their
      own respective groups (P < 0.05). Proliferating rates of HAEC were 17.1%, 15.1%,
      9.3%, 6.2%, 4.8%, 3.6%, 2.0% and 1.2% respectively by TGF-beta(1) of different
      cultured concentration (0.1 ng/ml, 0.2 ng/ml, 0.4 ng/ml, 0.8 ng/ml, 1.6 ng/ml,
      3.2 ng/ml, 6.4 ng/ml and 12.8 ng/ml). Proliferating rates of HAEC in TGF-beta(1)
      groups (TGF-beta(1) concentration ranging from 0.8 ng/ml to 12.8 ng/ml) were
      significantly lower than that in the control group (P < 0.05). CONCLUSIONS: HAEC
      could transit and grow on the matrix of fibrin clot and repair the damaged area.
      EGF and bFGF could obviously stimulate HAEC proliferation, while TGF-beta(1)
      might have the inhibitive effects.

PMID- 16635321
TI  - [Effects of routine early amniotomy on labor and health status of foetus and
      neonate: a meta-analysis].
AB  - OBJECTIVE: To analyze the effects of routine early amniotomy on labor and health
      status of foetus and neonate. METHODS: The results of Early amniotomy increases
      the frequency of fetal heart rate abnormalities, A randomized controlled trial of
      early amniotomy, Effect of early amniotomy on the risk of dystocia in nulliparous
      women, The influence of elective amniotomy on fetal heart rate patterns and the
      course of labor in term patients: A randomized study, Randomised trial comparing
      a policy of early with selective amniotomy in uncomplicated labour at term and A
      randomized controlled trial and meta-analysis of active management of labour were
      analyzed using Mantel-Haenszel method (fixed effect model) in meta-analysis.
      RESULTS: (1) The routine early amniotomy can shorten 94.90 min of the first stage
      of labor, 95% CI (-119.17, -70.52). (2) The OR for cesarean section was 1.25, 95%
      CI (0.99-1.57), for instrumental vaginal delivery was 1.05, 95% CI (0.90-1.24).
      (3) There was no difference in abnormal fetal heart rate at first stage (OR =
      0.95, 95% CI: 0.75-1.21), but there was increased abnormal fetal heart rate at
      second stage (OR = 1.28, 95% CI: 1.02-1.61). (4) The frequency of stained
      amniotic fluid and abnormal Apgar scores at 1 minute was not different
      significantly [OR = 1.17, 95% CI (0.78-1.73); OR = 0.71, 95% CI: (0.49-1.03)].
      CONCLUSIONS: Routine early amniotomy appears to be associated with both benefits
      and risks. Beneficial effects include reductions in labor duration and possible
      decrease in frequency of abnormal Apgar score at one minute. Risks include
      increase in abnormal fetal heart rate at second stage and possible rise in
      cesarean section rate.

PMID- 16635322
TI  - [Clinical significance of matrix metalloproteinase-9/tissue inhibitors of matrix
      metalloproteinase -1 imbalance in maternal serum, amniotic fluid, umbilical cord
      serum in patients with premature rupture of the membranes].
AB  - OBJECTIVE: To investigate the roles of matrix metalloproteinase (MMP)-9 and
      tissue inhibitors of matrix metalloproteinase (TIMP)-1 in maternal serum,
      amniotic fluid and umbilical cord serum in predicting premature rupture of the
      membranes (PROM) and chorioamnionitis. METHODS: The levels of MMP-9 and TIMP-1
      were detected by enzyme linked immunosorbent assay in maternal serum, amniotic
      fluid, umbilical cord serum of 58 pregnant women with PROM and 38 women with
      normal pregnancies. Chorioamnionitis was histopathologically confirmed after
      delivery. RESULTS: (1) The levels of MMP-9 in maternal serum, umbilical cord
      serum and amniotic fluid were (141.9 +/- 84.6) ng/L, (138.2 +/- 81.4) ng/L and
      (85.6 +/- 27.5) ng/L respectively, significantly higher in patients with PROM
      than those of the control group (P < 0.05, P < 0.05 and P < 0.01 respectively),
      while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord
      serum were (378.1 +/- 220.2) ng/L, (44.6 +/- 24.0) ng/L and (257.2 +/- 98.8) ng/L
      respectively, significantly lower in patients with PROM than those of the control
      group (P < 0.05, P < 0.05 and P < 0.01 respectively). (2) The longer the duration
      from rupture of membranes to delivery was, the more serious chorioamnionitis was,
      and the higher the levels of MMP-9 and the lower the TIMP-1 levels in maternal
      serum, amniotic fluid, and umbilical cord serum were. (3) The levels of MMP-9 in
      maternal serum, umbilical cord serum and amniotic fluid were (183.8 +/- 84.7)
      ng/L, (171.2 +/- 92.9) ng/L and (95.5 +/- 21.1) ng/L respectively, significantly
      higher in patients with chorioamnionitis than those of non-chorioamnionitis (P <
      0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal
      serum, amniotic fluid and umbilical cord serum were (269.7 +/- 144.4) ng/L, (32.1
      +/- 16.6) ng/L and (210.6 +/- 81.9) ng/L respectively, significantly lower in
      patients with chorioamnionitis than those of non-chorioamnionitis (P < 0.05, P <
      0.05 and P < 0.01 respectively). (4) The levels of MMP-9 in maternal serum,
      umbilical cord serum and amniotic fluid were (234.4 +/- 79.4) ng/L, (222.1 +/-
      120.1) ng/L and (108.5 +/- 42.2) ng/L respectively, significantly higher in
      neonates whose Apgar score < or = 7 than those of neonates whose Apgar score > or
      = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in
      maternal serum, amniotic fluid and umbilical cord serum were (225.3 +/- 121.7)
      ng/L, (25.2 +/- 15.8) and (181.7 +/- 135.2) ng/L respectively, significantly
      lower in neonates whose Apgar score < or = 7 than those of neonates whose Apgar
      score > or = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively). CONCLUSIONS: It is
      suggested that preterm PROM is associated with increased MMP-9 and decreased TIMP
      1 levels. MMP-9 and TIMP-1 are valuable clinical biological markers for
      identifying chorioamnionitis and predicting neonates prognosis.

PMID- 16635323
TI  - [Study of the injury to the urinary system caused by radiological vascular
      interventional therapy of obstetrical and gynecological benign diseases].
AB  - OBJECTIVE: To explore the injuries to the urinary system caused by uterine artery
      embolization (UAE) for treatment of obstetrical and gynecological benign
      diseases, including the classification, aetiology, therapy of the injuries and
      precaution methods. METHODS: The injuries of the urinary system were reviewed in
      960 cases of obstetrical and gynecological benign diseases treated with UAE by
      our interventional centre. Of all 960 cases, 690 cases were myoma, 244
      adenomyosis, 8 cervical pregnancy, 2 cornus pregnancy, 14 postpartum hemorrhage,
      2 late postpartum hemorrhage. Meanwhile, the correlative problems of the vascular
      anatomy, DSA and the embolization technics of microcatheter were analyzed.
      RESULTS: (1) Different degrees of urinary system injuries occurred in 5 of 960
      cases, the rate was 0.5%. None was severe injury, one case (0.1%) was moderate
      injury, and the patient suffered of hydronephrosis caused by segmental necrosis
      of unilateral ureter. Mild injury occurred in 4 cases (0.4%), including one case
      of inflammation of bladder, one case of partial necrosis of bladder mucosa
      membrane, 2 cases of transient slight unilateral hydronephrosis. Among all the
      injuries, 4 occurred in myoma patients, and one occurred in adenomyosis patient.
      The operation procedures of all five cases were bilateral uterine artery
      embolization, and none used microcatheter. (2) The ureter branch arising from the
      middle or lower part of the uterine artery supplied the middle or lower part of
      ureter and the length of this part of ureter is about 4 cm, the bladder branch
      arising from the middle or lower part of uterine artery supplied the bladder and
      communicated with the bladder vascular net. Correlative injuries could be caused
      by the retroflow of embolisms into the above arteries. (3) Placement of the
      catheter into the upper branch of the uterine artery or the tumor vascular net,
      using microcatheter if necessary and notation of the retroflow in the
      embolization process could avoid the embolization of bladder and ureter arteries.
      (4) Totally 506 cases used microcatheter, the ratio was 52.7%. The 5 cases of
      injuries did not use microcatheter. CONCLUSIONS: Injuries to the urinary system
      could occur in UAE for treatment of obstetrical and gynecological benign
      diseases, which can be prevented by carefully differentiating the vascular
      communicating branch and the conditions of branches, and embolization of the
      upper branch of uterine artery can avoid the injury.

PMID- 16635325
TI  - [Expressions of matrix metalloproteinase-9 and tissue inhibitor of
      metalloproteinase-1 mRNA in endometriosis].
AB  - OBJECTIVE: To investigate mRNA expression of matrix metalloproteinase (MMP-9) and
      tissue inhibitor of metalloproteinase (TIMP-1) in ectopic endometriosis tissue
      and uterine endometrium from women with and without endometriosis. METHODS:
      Thirty-eight women with endometriosis (Revised American Fertility Society
      classification, RAFSI-IV) were selected as study group. Thirty-eight specimens of
      ovarian endometrioma (ovarian chocolate cysts, OCC), 16 red peritoneal
      endometriotic lesions (RPL), and 35 matched eutopic endometrium (Eu) were
      collected from them simultaneously at the time of surgery. Twenty specimens of
      endometrium from reproductive women undergoing laparoscopic surgery without
      endometriosis were obtained as control group. The mRNA expressions of MMP-9 and
      TIMP-1 were detected by reverse transcription polymerase chain reaction (RT-PCR).
      RESULTS: Expression of TIMP-1 mRNA was detected in all samples. The level from
      endometriosis patients and control group was similar (2.31 +/- 1.21, 2.40 +/-
      0.89). However, ectopic endometrium expressed significantly fewer TIMP-1 mRNA
      (OCC 1.67 +/- 0.79, RPL 1.45 +/- 0.68) compared with eutopic endometrium from
      both endometriosis and endometriosis-free patients (P < 0.05). The positive
      expression rate of MMP-9 mRNA was not distinctively different among all samples.
      The density of MMP-9 mRNA expression in endometrium (0.49 +/- 0.28) from
      endometriosis patients was similar to that in ectopic endometriosis (OCC 0.46 +/-
      0.22, RPL 0.33 +/- 0.12), but was significantly higher compared with endometrium
      (0.29 +/- 0.12) without endometriosis (P < 0.05). CONCLUSIONS: An increase of MMP
      9 mRNA expression of eutopic endometrium with endometriosis might enhance the
      endometrial implantation ability, thus facilitate the ectopic implantation of
      endometrium. Ectopic lesions express significantly less TIMP-1 mRNA, indicating
      they have increased invasive ability, which might facilitate the development of
      endometriosis.

PMID- 16635326
TI  - [Combining high-risk human papillomavirus DNA test and cytological test to detect
      early cervical dysplasia].
AB  - OBJECTIVE: To assess the value of combining high-risk human papillomavirus (HPV)
      DNA test and cytological test in detection of early cervical dysplasia. METHODS:
      During January 2003 to June 2004, a total of 5210 women were screened by
      combining high-risk HPV DNA test (hybrid capture II, HC-II) and cytological test
      (liquid-based ThinPrep cytology test), and the abnormal cytological or HPV DNA
      findings were further biopsied under the colposcope. RESULTS: The age of the
      patients was between 17 to 80, the average was 34 +/- 9. Final pathological
      diagnosis was HPV infection in 890 cases, cervical intraepithelial neoplasia
      (CIN) I in 83 cases, CIN II in 73 cases, CIN III in 80 cases, invasive cervical
      cancer in 54 cases, endometrial cancer in 5 cases, vaginal intraepithelial
      neoplasia in 1 case and cervical tuberculosis in 1 case. Based on the criteria of
      histology and pathology, the sensitivity, specificity, positive-predictive value
      and negative-predictive value of high-risk HPV DNA test for detecting all cases
      of CIN II, III were 92.22%, 74.71%, 5.19% and 99.84% respectively. In detecting
      all cases of CIN II, III by cytological test, for atypical squamous cell of
      undetermined signification (ASCUS), the sensitivity, specificity, positive
      predictive value and negative-predictive value were 90.00%, 80.34%, 11.94% and
      99.63% respectively; for low-grade squamous intraepithelial lesion (LSIL), the
      sensitivity, specificity, positive-predictive value and negative-predictive value
      were 70.13%, 91.58%, 11.11% and 99.51% respectively; for high-grade squamous
      intraepithelial lesion (HSIL), the sensitivity, specificity, positive-predictive
      value and negative-predictive value were 48.05%, 98.46%, 31.90% and 99.21%
      respectively. By the combination of high-risk HPV DNA test and cytological test,
      the sensitivity, specificity, positive-predictive value and negative-predictive
      value for detecting all cases of CIN II, III were 98.70%, 73.08%, 5.21% and
      100.00% respectively. The infection rate of HPV in cervical cancer was 85.2%
      (46/54), in CIN III 92.5% (74/80), in CIN II 86.3% (63/73) and in CIN I 45.8%
      (38/83). CONCLUSIONS: High-risk HPV DNA test has high sensitivity and negative
      predictive value. The combination of high-risk HPV DNA test and cytological test
      increases the sensitivity and negative-predictive value, but it does not increase
      the specificity. The performance of biopsy under the colposcope can help the
      diagnosis of cervical dysplasia.

PMID- 16635327
TI  - [Study of differential gene expression in different stage human endometrial
      cancer].
AB  - OBJECTIVE: To study the gene expression profile of different stage endometrial
      cancer and identify genes related to the progression and metastasis of
      endometrial cancer. METHODS: cDNA microarray was used to analyze the
      differentially expressed genes between different stage endometrial cancers. The
      hierarchical cluster analysis was applied to the gene expression profile of 32
      endometrial cancers. RESULTS: Twelve differentially expressed genes were
      identified between different stage endometrial cancers. The conformity rate was
      66% between the result of hierarchical cluster analysis and the operative
      histological stages of International Federation of Gynecology and Obstetrics
      (FIGO). CONCLUSION: Genes related to the endometrial cancer progression and
      metastasis can be identified by differential gene expression profile with cDNA
      microarray and high-risk endometrial cancer may be distinguished before surgery
      by hierarchical cluster analysis.

PMID- 16635328
TI  - [Application research on the flow-through hybridization and gene chip in human
      papillomavirus detection].
AB  - OBJECTIVE: To evaluate the clinical efficacy of flow-through hybridization and
      gene chip (HybriMax) on female low genital human papillomavirus (HPV) detection
      and to identify the most common HPV genotypes. METHODS: Five hundred and ninety
      one of 7520 women who received cervical cancer screening in China-Japan
      Friendship Hospital during Jun 2004 to May 2005 were selected for 21 genotypes
      HPV detecting by HybriMax, including 138 women with normal cytological diagnosis
      and 453 women with abnormal cytological diagnosis. The abnormal patients were
      classified into groups according to their histological diagnosis as chronic
      cervicitis, cervical intraepithelial neoplasia (CIN) I, II, III, cervical cancer
      and condyloma acuminata. Among them 413 women were tested with HC-II for 13 types
      of high-risk HPV, and 101 paraffin-embedded specimens from these 453 patients
      were detected for HPV16, 18 with in situ hybridization (ISH). The accordance of
      the results was compared. The infection rates of each HPV type for each group
      were calculated. RESULTS: The total accordant rate of HybriMax and HC-II on 13
      types of high-risk HPV detecting was 92.5% (382/413) and was 100.0% in group of
      cancer. The accordance was good, and the Kappa index (KI) was as below: overall
      0.814, in normal group 0.750, in chronic cervicitis 0.781, in CIN I 0.755, in CIN
      II 0.619, in CIN III 0.548, in condyloma acuminata 0.800. The accordant rate of
      HybriMax and ISH was 89.1% (90/101), and KI was 0.766. The 10 most common
      genotypes were (in descending sequences): in normal group 16, 68, 18, 52, 58, 11,
      53, 31, 39, 33; in abnormal group 16, 52, 58, 18, 33, 31, 81, 53, 68, 66, in
      cervical cancer 16, 18, 52, 58, 33, 66, 68, 31, 51, 53. CONCLUSIONS: HybriMax has
      good accordance to HC-II and ISH for HPV detection. It provides useful
      information on viral genotype and is more suitable for clinical use. The 6 most
      common genotypes in abnormal cytological group are 16, 18, 52, 58, 33, 31.

PMID- 16635329
TI  - [Study on mRNA expression of the human novel gene NM23-H1B in ovarian tumor].
AB  - OBJECTIVE: To study the expression of the human novel gene NM23-H1B in ovarian
      cancer. METHODS: Forty-eight samples from patients with ovarian tumor at
      different clinical stages and 8 from normal ovaries were examined for NM23-H1B
      mRNA expression by using RT-PCR, northern blot and in situ hybridization.
      RESULTS: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of
      expression in ovarian tumor was higher than that of normal ovary. The level of
      expression in early stage (stage I and II) cancer was higher than in advanced
      (stage III and IV) cancer. The results of northern blot showed that NM23-H1B was
      over expressed in ovarian cancer while low expressed in normal ovary or low
      malignant potential (LMP) ovarian cancer. In early stage carcinoma, the
      expression level was related with the differentiation of tumor cell. Well
      differentiated cancer expressed NM23-H1B mRNA at comparatively higher level. The
      result of in situ hybridization showed that positive expression rate of NM23-H1B
      mRNA in ovarian cancer (100%, 40/40) was significantly higher than that in normal
      ovary (0/8) or LMP ovarian cancer (2/8). CONCLUSION: The novel gene NM23-H1B is
      related to ovarian cancer.

PMID- 16635330
TI  - [Study of immunization protocol of ovarian carcinoma associated 6B11 anti
      idiotypical minibody].
AB  - OBJECTIVE: To probe better immunization dose and interval of anti-idiotypical
      minibody (6B11 minibody) in animals and to guide the clinical trials of ovarian
      epithelial cancer treatment. METHODS: Minibody was induced with
      isopropylthiogalactoside (IPTG) in E.coli and analyzed with direct enzyme linked
      immunosorbent assay (ELISA). Normal BALB/c mice were randomly divided into groups
      A, B, C, D, E, F, immunized with the murine monoclonal anti-idiotypic antibody
      6B11 minibody 150 microg, 100 microg, 50 microg, and mice IgG 100 microg, human
      IgG 100 microg, phosphate buffered saline (PBS) 100 microl at d(1), d(14), d(28)
      respectively. Anti-anti-idiotypic antibody (Ab3) level was tested and antibody
      dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity
      (CDC) effect of mouse spleen cells to human ovarian carcinoma SKOV3 cells were
      measured using (51)Cr-release assay. UV absorption values were tested at 490 nm.
      RESULTS: 6B11 minibody was successfully expressed on E.coli and could react with
      a murine monoclonal antibody COC166-9. Ab3 could not be detected until one week
      after d(14)'s boost, its level gradually elevated and peaked one week after
      d(28)'s boost, and maintained at high level for about six weeks then declined
      dramatically seven weeks after d(28)'s boost. When boosted again at seven weeks
      after d(28)'s boost, the Ab3 level elevated quickly one week after, and
      maintained at this level at least for two weeks. The Ab3 level of group B was
      higher than groups A and C, mean A (absorption) value during six weeks after
      d(28)'s boost was 1.05 in group A, 1.06 in group B, 0.94 in group C, and there
      was no significant difference (P > 0.05). At four different effector cell/target
      cell (E/T) ratios, the ADCC was highest in group A and lowest in group C; when
      the E/T ratio was 1:125, (51)Cr releasing rate was 23% in group A, 17% in group
      B, and 12% in group C, the difference between groups A, B, C had statistical
      significance (P < 0.05). When serum was diluted at 1:50, the CDC effects were
      higher in group A and B than in group C ((51)Cr releasing rate was 47%, 39%, 26%
      respectively; P < 0.05), but there was no significant difference between groups A
      and B (P > 0.05). CONCLUSION: 6B11 anti-idiotypic minibody of ovarian carcinoma
      can be used as tumor vaccine, the suitable immunization protocol in animals may
      be: prime at d(1), d(14) and d(28) at a dose of 100 microg; prime interval is six
      weeks.

PMID- 16635331
TI  - [Primary study on fusions of ovarian carcinoma cells to dendritic cell
      transfected with interleukin-12 gene in vitro].
AB  - OBJECTIVE: To investigate the immune response of the fusions of ovarian carcinoma
      cells to dendritic cell (DC) transfected with interleukin (IL)-12 gene in vitro.
      METHODS: Recombinant human granulocyte macrophage colony stimulating factor and
      recombinant human tumor necrosis factor alpha were used to generate DC from cord
      blood in vitro. IL-12 fusion gene was cloned into a eukaryotic vector-pcDNA3.1
      (+). DC were transfected with IL-12-pcDNA3.1 (+) using lipofectamine transfection
      method and electric transfection method respectively. Then polyethylene glycol
      mediated the fusion of transfected DC and ovarian carcinoma cells, and 3-(4, 5
      dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) test was carried
      out to observe the immune response. RESULTS: DC were generated in vitro from cord
      blood and expressed high levels of costimulatory (50%) and MHC II molecules
      (99%). RT-PCR showed that IL-12-pcDNA3.1 (+) had been successfully transfected
      into DC. RT-PCR and immunofluorescence analysis showed that DC were fused with
      ovarian carcinoma cells successfully. Then the fusion cells of ovarian carcinoma
      cells to transfected DC, and the fusions of ovarian carcinoma cells to DC were
      cocultured with peripheral blood mononuclear cell respectively. MTT test showed
      that both fusions could induce cytolytic T cell activity and lysis of ovarian
      carcinoma cells, and the former effect was stronger. CONCLUSION: The cytolytic T
      cell activity induced by the fusions of ovarian carcinoma cells to transfected DC
      is enhanced.

PMID- 16635340
TI  - [Safety of donor of right lobe graft in living donor liver transplantation].
AB  - OBJECTIVE: To evaluate the safety of donors of right lobe graft. METHODS: We
      retrospectively studied 13 living donors of right lobe graft from January 2002 to
      June 2005. The right lobe grafts were obtained by transecting the liver on the
      right side of the middle hepatic vein. Liver transection was done by using an
      ultrasonic dissector without inflow vascular occlusion. The standard liver volume
      and the ratio of left lobe volume to the standard liver volume were calculated.
      RESULTS: The mean blood loss was 490 ml. The mean blood transfusion was 440 ml.
      In the perioperative period the mean albumin administered was 85 g. One donor had
      portal vein trifurcation, two had a right posterior bile duct and a right
      anterior bile duct draining into the left bile duct, respectively. One had bile
      ducts from left lateral and left internal segment and right duct draining into
      common hepatic duct. On postoperative day 1 the donors' liver functions were
      found impaired to some extent, but all the indices rapidly returned to the normal
      level at the end of the first week. Postoperative complications included 1 case
      of abdominal bleeding, 2 wound steatosis and 1 chyle leak. There was no donor
      mortality. All donors are well and have returned to their previous occupations.
      CONCLUSIONS: The donation of right lobe graft for adult living donor liver
      transplantation is safe provided that the patency of the remnant hepatic
      vasculature and bile duct is ensured, the volume of the remnant liver exceeds 30%
      of the total liver volume, and there is no injury to the remnant liver.

PMID- 16635341
TI  - [Retransplantation for liver transplanter with poor graft function].
AB  - OBJECTIVE: To summarize the experience of liver retransplantation for patients
      with poor graft function. METHODS: The clinical data of 9 patients undergone
      liver retransplantation at our center from April 1993 to April 2005 were
      retrospectively analyzed. The main indications for liver retransplantation at our
      center were early hepatic artery thrombosis (2/9), early portal vein thrombosis
      (1/9), and biliary tract complication (6/9). Of the 9 patients received liver
      retransplantation with cadaveric allografts, 3 received classic orthotopic liver
      transplantation, and 6 piggyback liver transplantation. Roux-en-Y biliary tract
      reconstruction was performed in 6 patients, Donor spleen vein was used as a
      conduit between donor portal vein and recipient portal vein in 1, and donor
      spleen artery as a conduit between donor hepatic artery and recipient aorta in 1.
      RESULTS: No perioperative mortality occurred. Of them, 5 had no complications
      after the operation, 1 had stricture in anastomotic stoma of portal vein, and 3
      died in 6 months after the operation. CONCLUSIONS: Poor graft function due to
      biliary tract complications and vessel complications after primary liver
      transplantation are the chief indications of liver retransplantation. Liver
      retransplantation is the only suitable treatment of poor graft function.

PMID- 16635342
TI  - [Simultaneous liver-pancreas-duodenum transplantation: one case report and review
      of the literature].
AB  - OBJECTIVE: To investigate the effect of treatment on end-stage liver disease and
      type-I diabetes mellitus with simultaneous liver-pancreas-duodenum
      transplantation. METHOD: In September 2003, one patient with chronic hepatitis B,
      liver cirrhosis, hepatic cellular cancer, and insulin-dependent diabetes received
      simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation.
      Liver and pancreas graft function was monitored after transplantation. RESULTS:
      The function of pancreas allograft was recovered immediately and the patient
      became insulin-independence postoperatively. The liver allograft was experienced
      an acute rejection episode and reversed by intravenous bolus methylprednisolone.
      The recipient was currently liver disease-free and insulin-free more than 21
      months. CONCLUSIONS: The simultaneous liver-pancreas-duodenum transplantation is
      an effective method in the treatment of end-stage liver disease and type-I
      diabetes mellitus.

PMID- 16635343
TI  - [Ultrastructure study on patients with spontaneous rupture of hepatocellular
      carcinoma].
AB  - OBJECTIVE: To investigate the ultrastructure of small artery wall in patients
      with spontaneous rupture of hepatocellular carcinoma (HCC). METHODS: Transmission
      electron microscopy was used to study 11 specimens from ruptured HCC and 11 cases
      with non-ruptured HCC. RESULTS: The phenomenon of activated phagocytosis in
      macrophage could be found in 3 cases with ruptured HCC and 10 cases with non
      ruptured HCC, respectively (P < 0.05). In 9 specimens with ruptured HCC, the
      evidence of vascular injury characterized as less cell junctions and larger
      fenestrae in endothelial cells, broken elastic lamina, proliferated and
      fragmented elastin and damaged structure of collagen was found in small arteries.
      The phenomenon of electron-dense deposit in the elastic lamina, and signs of more
      protein synthesis in endothelial cells were also present in these specimens. In
      the patients with non-ruptured HCC, the evidence of vascular injury can be found
      only in 2 cases (P < 0.01). Less cell junctions and larger fenestrae could
      increase the permeability of vascular wall. The electron-dense deposition in
      elastic lamina may represent the deposition of antigen-antibody complex in
      elastic membrane which had been found in our previous study. The vascular injury
      was postulated to be caused by the deposition of antigen-antibody complex in
      vascular wall which was identified by our previous study. The vascular wall in
      the patient with ruptured HCC could become stiff and weak due to the proliferated
      fragment elastin and damaged collagen which would make the blood vessels more
      prone to splitting and result in hemorrhage and the rupture of HCC. CONCLUSIONS:
      The vascular injury caused by antigen-antibody complex deposition might related
      to the spontaneous rupture of HCC.

PMID- 16635344
TI  - [Surgical treatment of pancreatic insulinoma by laparoscopy].
AB  - OBJECTIVE: To evaluate the safety and outcome of laparoscopic insulinoma
      resection. METHODS: Twenty-five patients with insulinoma were admitted and
      divided into two groups: laparoscopic group (10 patients) and laparotomy group
      (15 patients). All tumors of two groups were located at the body or tail of
      pancreas preoperatively by abdominal CT and digital subtraction angiography
      (DSA). Laparoscopic enucleation was performed for patients in laparoscopic group,
      open enucleation was performed for patients in laparotomy group. There were no
      differences in preoperative location and size of tumors between two groups.
      Statistical method was used to compare the discrepancy from operation time, the
      volume of blood loss, hospital stay and morbidity of complication between two
      groups. RESULTS: There were no discrepancies from operation time, blood loss,
      hospital stay after operation between two groups (P > 0.05). However, one case of
      pancreatic leakage developed in laparoscopic group, comparably, 3 cases of
      pancreatic leakage, 2 cases of celiac sepsis and 5 cases of fluid accumulation in
      thoracic cavity developed in laparotomy group. There were significant
      discrepancies in morbidity of complication between two groups. CONCLUSIONS:
      Laparoscopic resection of pancreatic insulinoma is safe and feasible for tumors
      located at the body or tail of the pancreas. Its application for tumors located
      at the pancreatic head needs further evaluation.

PMID- 16635345
TI  - [Survival and prognostic analysis of radiofrequency ablation of hepatocellular
      carcinoma].
AB  - OBJECTIVE: To assess the survival of radiofrequency ablation (RFA) and
      investigate the prognostic factors affecting overall survival, local recurrence
      free survival and disease-free survival in hepatocellular carcinoma (HCC).
      METHODS: A total of 192 HCC patients underwent RFA treatment in our department
      and were enrolled into this study. Among them, 151 patients were males and 41
      were females (mean age, 59.2 years, range, 24 - 87 years old). The average tumor
      size was (3.9 +/- 1.3) cm (range, 1.2 - 8.0 cm). Of these 192 HCC patients, their
      Child-Pugh grade of A, B and C were 106, 77 and 9, respectively. According to
      UICC-TNM system, 57, 85, 44 and 6 patients were in stage I, II, III and IV
      respectively. Kaplan-Meier model and log-rank test were used in univariate
      analysis and COX regression model was used in multivariate analysis to identify
      prognostic factors for survival. RESULTS: The 1-, 2-, 3- and 4-year overall
      survival were 84.9%, 69.1%, 60.4% and 52.8%, respectively. Local recurrence-free
      survival were 75.1%, 53.8%, 43.9% and 40.8%, respectively. Disease-free survival
      were 64.3%, 43.2%, 37.1% and 25.0%, respectively. The following factors were
      identified as independent prognostic factors for survival by multivariate model:
      (1) Overall survival: Child-Pugh classification, standard treatment protocol and
      UICC-TNM staging. (2) Local recurrence-free survival: Child-Pugh classification
      and UICC-TNM staging. (3) Disease-free survival: UICC-TNM staging, Child-Pugh
      classification and daughter lesion. Among these, both Child-Pugh classification
      and UICC-TNM staging were independent prognostic factors for three kinds of
      survivals. CONCLUSIONS: Degree of tumor progress (UICC-TNM stage, daughter
      lesion), treatment method (applying of standard treatment protocol) and patients'
      liver function are the most important factors for survival after RFA. So
      application of proper treatment strategy before, during and after RFA should be
      required to improve survival.

PMID- 16635346
TI  - [Analysis of patterns, intervals and risk factors for recurrent gastric cancer].
AB  - OBJECTIVE: To explore the patterns, intervals, risk factors of recurrent gastric
      cancer and provide evidences for predicting and prevention of recurrence after
      curative gastrectomy. METHODS: Forty-eight patients with recurrent gastric cancer
      after curative gastrectomy for gastric cancer who were operated on in our
      department from August 1994 to August 1999 were enrolled in this study. Their
      recurrent patterns, intervals and clinicopathologic characters of primary tumors
      were analyzed retrospectively and compared with 48 cases without recurrence, who
      were treated homeochronously and chosen randomly. Risk factors correlated with
      tumor recurrence and recurrent intervals were studied by univariate and
      multivariate analysis. RESULTS: Univariate analysis showed that patients with
      metastases node in pelvic cavity, cancer invasion to serosa or more, Borrmann III
      or IV types were more occurred in recurrent group (P < 0.05). Multivariate
      analysis showed the depth of cancer invasion and Borrmann types were
      independently correlated with tumor recurrence after curative gastrectomy. COX
      regression analysis showed ascites and depth of cancer invasion were parameters
      dominating recurrent interval. CONCLUSIONS: Borrmann type is a risk factor of
      gastric cancer recurrence, while ascites is a parameter dominating recurrent
      interval, and the depth of cancer invasion is both risk factor of gastric cancer
      recurrence and parameter dominating recurrent interval.

PMID- 16635347
TI  - [The pathological characters and its clinical significance of internal
      hemorrhoids].
AB  - OBJECTIVE: To investigate the pathological characters and the corresponding
      clinical significance of internal hemorrhoids tissues. METHODS: Normal anal
      cushion and internal haemorrhoids tissue samples were obtained after stapled
      haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The
      macroscopically normal cushions served as own controls and the normal cushions
      from a patient without a history of haemorrhoids as quality control. Routine
      Hematoxylin-Eosin and orcein were performed for elastic fibers. RESULTS: Compared
      with the corresponding normal anal cushions, the subepithelial vessels especially
      the cavernous vessels of the hemorrhoidal tissues showed obvious structural
      impair, retrograde changes, and the internal elastic lamina were ruptured and
      discontinuous. In addition, thrombosis and subsequent ischemic changes were
      observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy,
      distortion, rupture and tortility. Obvious mucosal injury was observed in the
      mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the
      hemorrhoidal tissues. CONCLUSIONS: The anal cushions of hemorrhoids disease
      patients show significant pathological changes. The pathological changes include
      structural impair, retrograde changes of the cavernous vessels and the
      hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the
      fibroelastic tissues, and mucosal injury of the mucous membranes. These
      pathological changes are the basis of pathogenesis and development of
      hemorrhoids.

PMID- 16635348
TI  - [Lymph node micrometastases and expression of metastasis-related gene proteins in
      patients with colorectal cancer].
AB  - OBJECTIVE: To study lymph node micrometastases (LNMM), expression of nm23-H(1),
      MMP(9), TIMP(2) proteins, and their relationship and clinical significance in
      patients with stage Dukes B colorectal cancer. METHODS: Thirty patients with
      stage Dukes B colorectal cancer were studied. LNMM in these patients was detected
      by immunohistochemical anti-cytokeratin 20 (CK20) staining. The expression of
      nm23-H(1), MMP(9) and TIMP(2) proteins in primary tumors was examined by Strept
      avidin-biotin complex method. Clinical-pathological data and survival of each
      patient were recorded and analyzed. RESULTS: (1) The positive dyeing of CK20 was
      observed in 26.7% for cases and in 7.8% for lymph nodes of 30 patients with stage
      Dukes B colorectal cancer. (2) Different expression of nm23-H(1) and MMP(9)
      proteins in the patients between stage Dukes B and stage Dukes CD was observed (P
      < 0.05). The decreased nm23-H(1) expression, and/or the increased MMP(9)
      expression in primary stage Dukes B tumors were significantly associated with
      LNMM (P < 0.05). Sensitivity and specificity for detection of LNMM by using nm23
      H(1) or MMP(9) were respectively 62.5% and 81.8% or 75.0% and 69.8%. If by
      combining nm23-H(1) with MMP(9), specificity for detection of LNMM became 90.9%.
      The expression of TIMP(2) protein was not related with stage Dukes and LNMM. (3)
      The percent of tumor recurrence and/or metastasis for the stage Dukes B patients
      with LNMM was significantly higher than that for the patients without LNMM (P <
      0.05), but the survival percent for the patients with LNMM was significantly
      lower than that for the patients without LNMM. The outcome for the patients with
      nm23-H(1) (-) LNMM (+) or MMP(9) (+) LNMM (+) was significantly worse than that
      for patients with nm23-H(1) (+) LNMM (-) or MMP(9) (+) LNMM (-) (P < 0.05).
      CONCLUSIONS: LNMM is detected by immunohistochemical anti-CK20 staining. The
      expression of nm23-H(1) and MMP(9) in primary stage Dukes B tumors was
      significantly associated with LNMM. The outcome in the LNMM patients with nm23
      H(1) (-) and/or MMP(9) (+) were worse. Combining examination of CK20 for lymph
      nodes with expression of nm23-H(1) and MMP(9) for primary tumors is of important
      clinical significance for staging of Dukes, selection of adjuvant treatment and
      evaluation of prognosis in patients with colorectal cancer.

PMID- 16635349
TI  - [Role of urinary basic fibroblast growth factor in differentiating hemangiomas
      from vascular malformation].
AB  - OBJECTIVE: To investigate a novel method to differentiate hemangioma from
      vascular malformation, to stage hemangiomas and to monitor the efficacy of
      management for hemangioma. METHODS: The urinary basic fibroblast growth factor
      (bFGF) concentration of 144 cases (including 69 cases of proliferating
      hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular
      malformations and 11 negative controls) was examined using enzyme linked
      immunosorbent assay (ELISA). RESULTS: The differences of urinary bFGF
      concentration among proliferating hemangiomas, involuting hemangiomas, vascular
      malformations and negative control were all significant, while the differences
      between the latter three groups were not significant. CONCLUSIONS: Our findings
      suggest that examination of urinary bFGF concentration using ELISA technique is
      helpful in differentiating hemangioma from vascular malformation, staging
      hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas.
      Our results probably shed new light on the potential pathogenesis of hemangiomas
      and vascular malformation.

PMID- 16635350
TI  - [The mechanism and treatment phases chosen of glycine for inhibition
      lipopolysaccharide induced Kupffer cells activation].
AB  - OBJECTIVE: To explore the possible mechanism and optimal treatment phase of
      glycine for inhibition lipopolysaccharide (LPS) induced Kupffer cells (KCs)
      activation. METHODS: The KCs were isolated from 40 BALB/c mice and divided into
      four groups: the endotoxin group, the prevention group, the early treatment group
      and the later treatment group (n = 10). The endotoxin group was treated with 10
      mg/L LPS, and in the other three groups, glycine (1 mmol/L) was given 24 h
      before, or at 0 h or 4 h respectively after LPS stimulation. At 0 h, 1 h, 2 h, 6
      h and 12 h after LPS stimulation, the mRNA levels and protein expression of
      interleukin-1 receptor associated kinase-4 (IRAK-4) were determined by reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot respectively,
      and nuclear factor-kappaB (NF-kappaB) activities as well as tumor necrosis factor
      alpha (TNF-alpha) levels were also detected by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The climax values of IRAK-4, NF-kappaB and TNF-alpha were
      significantly higher in the endotoxin group and the later treatment group than
      that in the other two groups (t = 3.17, 4.33, 2.47, 126.73, P < 0.01).
      CONCLUSION: The results indicated that prophylactic or simultaneous treatment
      with glycine could effectively inhibit LPS-induced KCs activation by inhibiting
      IRAK-4 expression.

PMID- 16635351
TI  - [Effect of inhibitors of signal transducer and activator of transcription-1/3 on
      expression of tumor necrosis factor-alpha induced by high mobility group box-1
      protein inflammatory response in rat peritoneal macrophages].
AB  - OBJECTIVE: To investigate the inflammatory signal transduction of high mobility
      group box-1 protein (HMGB1) induced inflammatory response in rat peritoneal
      macrophages. METHODS: Peritoneal macrophages obtained from male Wistar rats were
      seeded in 24-well (1 x 10(6) cells/well) tissue culture plates. The cells were
      incubated for 3 days before they were stimulated with HMGB1, and treated with
      Fludarabine [the specific inhibitor of signal transducer and activator of
      transcription 1 (STAT1)] or Rapamycin (the specific inhibitor of STAT3). The time
      dependent and dose-dependent responses between HMGB1 stimulation and tumor
      necrosis factor-alpha (TNF-alpha) gene expression as well as release were
      analyzed respectively. Moreover, the effect of Fludarabine and Rapamycin on TNF
      alpha mRNA expression and protein release were also observed. RESULTS: (1) After
      HMGB1 challenge, TNF-alpha mRNA expressions were up-regulated markedly, peaked at
      24 hours, and decreased at 36 hours. When HMGB1 was used at a concentration of 10
      microg/ml, TNF-alpha mRNA expression increased most markedly. (2) HMGB1 could
      induce TNF-alpha release in rat peritoneal macrophages, with peaking at 4 hours
      and decreasing at 8 hours later. When the concentration of HMGB1 stimulation
      increased from 5 microg/ml to 25 microg/ml, TNF-alpha release was persistently
      enhanced. (3) It was also showed that TNF-alpha mRNA expression was significantly
      inhibited by treatment of either Fludarabine (100 micromol/L) or Rapamycin (25
      ng/ml), while TNF-alpha release was not markedly suppressed. CONCLUSIONS: STAT1
      and STAT3 might be involved in the regulation of TNF-alpha gene expression, but
      not in TNF-alpha early release (< 24 hours) induced by HMGB1 stimulation in rat
      peritoneal macrophages.

PMID- 16635353
TI  - [Laparoscopic distal pancreatectomy with preservation of the spleen].
AB  - OBJECTIVE: To summarize the experience of laparoscopic distal pancreatectomy with
      preservation of the spleen. METHODS: From Nov 2003 to Dec 2004, 2 patients with
      cystic lesions in the body and tail of the pancreas underwent laparoscopic distal
      pancreatectomy with preservation of the spleen. RESULTS: Both of the operations
      were successful with the operative time of 220 min and 190 min respectively, and
      the blood loss were 450 ml and 350 ml. There was no postoperative complication
      and the pathological diagnosis was pancreatic serous cystadenoma. Both patients'
      symptom disappeared after operation without recurrence during the follow-up of 18
      and 5 months. CONCLUSION: Laparoscopic distal pancreatectomy with preservation of
      the spleen is safe and feasible for the management of benign tumor in the body
      and tail of pancreas with the advantages of reduced injury, earlier recovery and
      less complication.

PMID- 16635361
TI  - [Clinical outcome of anterior corrective surgery for thoracolumbar scoliosis:
      mini-open approach without diaphragm dissection versus open approach].
AB  - OBJECTIVE: To investigate the feasibility and clinical results of a new mini-open
      approach in the anterior instrumentation of thoracolumbar scoliosis by comparing
      with traditional open approach. METHODS: Seventy-two patients with the idiopathic
      thoracolumbar scoliosis underwent one stage anterior instrumentation and spinal
      fusion. In group A, the patients received anterior mini-open approach without
      dissecting diaphragm. There were total 34 cases with average age of 16 years old,
      ranging from 12 to 25 years. The average Cobb angle was 58 degrees with a range
      of 42 degrees to 76 degrees pre-operatively. The instrumentation levels were from
      T(11) to L(3) in 18 cases, T(11) to L(2) in 6 cases, T(11) to L(4) in 10 cases.
      In group B, the patients were treated with traditional open approach. Total 38
      cases with average age of 17 years old, ranging from 13 to 26 years, were
      included. The average Cobb angle was 54 degrees with a range of 40 degrees to 74
      degrees pre-operatively. The instrumentation levels were from T(10) to L(3) 7
      cases, T(11) to L(3) 20 cases, T(11) to L(4) 11 cases. RESULTS: In group A, the
      average curve correction was 81% with post-operative Cobb angle 12 degrees
      ranging from 4 to 16 degrees . Sagittal alignment restoration was satisfied in
      this group. In group B, the average curve correction was 73% with post-operative
      Cobb angle 15 degrees . The rehabilitation time was shorter in group A than in
      group B. No death, vascular injury and neurological complication occurred.
      Exudative pleurisy occurred in two patients in each group and cured very well.
      CONCLUSIONS: Mini-open anterior instrumentation for thoracolumbar scoliosis
      without diaphragm dissection is proved to have the same outcomes as the
      traditional anterior approach, without the increase of complication.

PMID- 16635362
TI  - [360 degrees fixation of lumbar spine].
AB  - OBJECTIVE: To estimate the effects of the treatment of 360 degrees fixation of
      lumbar spine. METHODS: Twenty-five cases were operated to 360 degrees fixation of
      lumbar spine from May 2002 to May 2005. There were 11 male and 14 female, the age
      ranging from 45 to 67 years, mean 56, including 16 cases of spondylolysis, 7
      cases of lumbar spinal instability and 2 cases of degenerative disc undergone
      with anterior laparoscopic lumbar interbody fusion with syncage and autograft and
      posterior decompression with facet fixation. The chief complains were low back
      pain and radiating to lag. Fourteen cases were fused at L(4), 5 and 11 cases at
      L(5)-S(1). The Oswestry Disability Index (ODI) were recorded to evaluate the
      function at pro-operation, the second week, the third, sixth and twelfth month
      post-operation. The X-ray was taken to observe the fusion and the sinking cage.
      RESULTS: The time intro-operation was from 110 to 180 minutes, mean 120 minutes.
      There was one complication in 1 case by the main vein injury. All of the 25 cases
      were followed-up post-operation from 12 to 35 months, mean 22.3 months. The ODI
      was found prominent difference compared with pro-operation in 2 weeks, 3, 6 and
      12 months post-operation (P < 0.05). Twenty-five cases were fused in the third
      month. Two cases sank 1 mm in the third month images but solid fusion. No cage
      displacement was found. No retrograde ejaculation happened. CONCLUSIONS: 360
      degrees fixation of lumbar spine adapts to deal with lumbar instability,
      degenerative disc disease and I, II degree spondylolysis. It shows less bleeding
      and injury, but during exposure and traction the main vessels should be very
      careful.

PMID- 16635363
TI  - [Research on complications of thoracoscopic assisted thoracic spine surgery].
AB  - OBJECTIVE: To analyze occurrence, prevention and treatment of the complications
      of thoracoscopic assisted spine surgery. METHODS: Retrospective review of 182
      patients who underwent standard thoracoscopic technique or video-assisted
      thoracic surgical procedure from October 1998 to August 2004. The treatment of
      thoracic diseases included debridement, decompression with (or) reconstruction.
      The total number of complications were recorded, and its mechanism, prevention
      and treatment were analyzed. RESULTS: Complications occurred in 16 patients, 12
      cases of perioperative complications included 3 patients suffered from pneumonia,
      3 pulmonary atelectasis, 2 patients' lung injured by trocar, 1 patient obtained
      transient monoplegia, 2 suffered from transient intercostal nerve pain and 1 had
      superficial incision infection. Long-term complications occurred in 4 cases:
      spinal tuberculosis relapsed 2 cases (one who had diabetes obtained relapse in 8
      months of post-operation and another relapsed with complex spinal tuberculosis in
      4 weeks postoperation), 2 patients suffered from kyphosis deformity and pain.
      CONCLUSIONS: The type and incidence of complications with thoracoscopic spine
      surgery mainly depend on indication, operation procedures and anesthesia, only by
      limit surgical indication, ameliorate technique, obey surgical principle and
      consummate perioperative treatment can we obtain mini-invasive effect by
      thoracoscopic assisted spine surgery.

PMID- 16635364
TI  - [The classification and its clinical value for extravertebral cement leakage
      complicated by percutaneous vertebral augmentation].
AB  - OBJECTIVE: To explore the category and its clinical value of extravertebral
      cement leakage complicated by percutaneous vertebroplasty and kyphoplasty.
      METHODS: After collecting clinical data of 56 patients underwent surgery of PVP
      or PKP between August 2001 and March 2005, extravertebral cement leakage was
      classified according to anatomical position, and its clinical value was analysed.
      RESULTS: Eighteen vertebraes presented cement leakage in all 43 vertebraes in PVP
      group. There were 15 vertebraes with one-place leakage, 6 vertebraes with
      perivertebral leakage, 5 spinal canal leakage, 2 intraforaminal leakage, 1
      intradical leakage and 1 paravertebral soft tissues leakage respectively among
      them; and there were 3 vertebraes with two-place leakage. Four vertebraes
      presented cement leakage in all 22 vertebraes in PKP group. All 4 vertebraes had
      one-place leakage including 2 vertebraes with perivertebral leakage, 1 spinal
      canal leakage and 1 intraforaminal leakage. Five patients with cement leakage
      presented new symptoms including peritoneal irritation signs and spinal cord or
      nerve root injury, 3 patients recovered after conservative treatment, whereas the
      other 2 patients need decompression surgery. CONCLUSIONS: The types of
      perivertebral leakage and spinal canal leakage are common among extravertebral
      cement leakage followed by percutaneous vertebroplasty and kyphoplasty. The
      minority of patients with cement leakage presents new symptoms, and the majority
      of them has the same therapeutic effect except patients with spinal canal leakage
      on one day after surgery.

PMID- 16635365
TI  - [The application of METRx microendoscopes diskectomy system in the treatment of
      far lateral lumbar disc herniation].
AB  - OBJECTIVE: To introduce the METRx microendoscopes diskectomy system in the
      treatment of far lateral lumbar disc herniation. METHODS: Fourteen cases of far
      lateral lumbar disc herniation were operated with METRx from February 1999 to
      December 2002. Among them, the average age was 49 years old (range 41 - 55 years
      old), male in 10 cases, female in 4 cases. All cases were single disc herniation;
      L(4), 5 herniation in 6 discs, L(5)-S(1) herniation in 8 discs; foraminal disc
      herniation in 6 cases, extra-foraminal disc herniation in 8 cases. RESULTS: All
      the cases were followed up from 12 to 46 months (average 26.5 months) with the
      results of excellence in 10 cases, good in 3 cases, fair in 1 case and no failure
      case. There were no disc infection, dura laceration, nerve root injury and
      herniation recurrence. CONCLUSIONS: METRx is suitable for far lateral lumbar disc
      herniation with the advantages of minimal invasive, complete decompression of
      nerve root and rapid recovery. The correct approach and precise surgical
      technique are the key points for this operation.

PMID- 16635366
TI  - [Clinical characteristics and treatment of flexion-distraction stage I injuries
      in subaxial cervical spine].
AB  - OBJECTIVE: To study the clinical characteristics and treatment of flexion
      distraction stage I injuries in subaxial cervical spine. METHODS: Twelve cases of
      flexion-distraction stage I injuries with delayed symptoms, admitted in our
      hospital between January 1995 and December 2004, were studied retrospectively. In
      acute phase, all of 12 cases had neck pain and limited neck movements,
      neurological deficits were found in 6 of 12 cases. Eight cases had a correct
      diagnosis, and 2 cases had a error diagnosis, 2 cases missed. All cases were
      satisfactory by the primary conservative treatment. After 274 days average
      asymptomatic intervals, all of 12 cases had recurrence of neck pain, delayed
      neurological deficits were found in 10. MRI showed that all of 12 cases were
      unstable injuries. RESULTS: All of the 12 patients were treated operatively.
      Decompression, fusion and fixation were performed by anterior approach in 9
      cases, and by combined anterior and posterior approach in 3 cases. The average
      follow-up period was 33.1 months. Neck pain had great recovery in all cases, 10
      cases with neurological deficits, 7 returned normal. Radiographic evidences of
      intervertebral bony fusion and good cervical alignment were observed in all of 12
      cases. CONCLUSIONS: Flexion-distraction stage I injuries is often caused by
      ligament and disc injuries, and often missed with subtle symptoms and
      radiographic changes. Inadequate primary treatment options are often due to
      failure to recognize the instability, and maybe result in delayed injuries. MRI
      is helpful for the early accurate evaluation of spinal stability. Unstable injury
      require early surgical treatment. The anterior approach operation is recommended
      to most of these patients with acute and old injuries. Combined anterior and
      posterior approach operation should be considered in these patients who have old
      injuries with stiff kyphosis.

PMID- 16635367
TI  - [The risk factors and preventive strategies of heterotopic ossification after
      artificial disc replacement in lumbar spine].
AB  - OBJECTIVE: To analyze the risk factors of heterotopic (HO) ossification after
      total lumbar disc replacement and probe the preventive strategies for it.
      METHODS: The radiographs and clinical data of 78 discs in 65 patients who
      received artificial lumbar disc replacement (ADR) from April 1998 to December
      2003 were analyzed retrospectively by two radiologists and one orthopaedic
      surgeon and then postoperative HO were graded according to McAfee system. The
      bony formations in disc spaces, time of HO were found, and range of motion (ROM)
      of the operated levels were measured on radiographic films. In addition, the risk
      factors such as preoperative peri-annulus ossification, bony endplates injuries,
      and subsided or mal-position of the prostheses were also analyzed by Logistic
      regression analysis. RESULTS: Postoperative HO was found in 10 spaces of 9 cases.
      Class I of HO were occurred in 7 patients at means 2.1 years postoperatively with
      normal range of motion preserved. Three of them turned into class II or III with
      10 degrees of mean ROM in the following 2.5 years. Another 2 (2/9) cases with
      preoperative peri-annulus ossification had bridging trabecular bone (class III)
      between the endplates and 9 degrees of ROM 2 years after surgery, then turned
      into class IV at 6 years with 0 degrees and 4 degrees of motion in the operated
      levels. As the risk factors of HO, preoperative annulus ossification (2 cases),
      bony endplates injuries (5 cases), mal-positioned prostheses (2 cases) and
      subsided prostheses (2 cases) were found simultaneity with significant positive
      relation to HO occurred (P < 0.05). CONCLUSIONS: Factors such as preoperative
      ossification of annulus, endplate injuries, prosthesis subsided and mal-position
      would have higher risks to have HO occurred after ADR, but ROM of most affected
      levels are preserved. Strict control indication and avoid all above risk factors
      can prevent HO occurring effectively.

PMID- 16635368
TI  - [Influence factors of adjacent segment degeneration after instrumented lumbar
      fusion].
AB  - OBJECTIVE: To investigate the influence factors of adjacent segment degeneration
      (ASD) after instrumented lumbar fusion. METHODS: Thirty-three patients who had
      undergone an instrumented lumbar fusion from March 1998 to May 2002 were
      reviewed. The incidence, age, position, radiographic characteristics and clinical
      manifestations of ASD were studied. Then the relations between "floating fusion"
      and ASD were compared, the range of fusion and ASD and investigated the
      incidences of different adjacent segments. RESULTS: The mean follow-up period for
      the patients was 4 years and 7 months (24 - 82 months). Adjacent segment
      degeneration mainly occurred in patients older than 60. Ten patients (10%) were
      found to have radiographic characteristics of ASD. Nine of the ten patients had
      ASD at cranial segments. Using "floating fusion" or not did not show difference
      in the risk of ASD. There was a trend of more ASDs after long-segment fusion than
      short-segment fusion. As an adjacent segment, L(2)/L(3) had a high risk of ASD,
      while L(5)/S(1) had a much lower risk. CONCLUSIONS: The cranial segment has a
      higher degeneration risk than the caudal segment. If L(2)/L(3) has degenerative
      appearance and has chance to be the adjacent segment, we'd better fuse it. If
      there is no evidence of obvious degeneration, L(5)/S(1) should not be fused.
      During instrumented lumbar fusion, long-segment fusion should be avoided if
      possible.

PMID- 16635369
TI  - [Arthroscopic rotator cuff repair for the treatment of rotator cuff tear].
AB  - OBJECTIVE: To discuss and evaluate the surgical techniques of arthroscopic
      rotator cuff repair and its clinical results. METHODS: From March 2002 to May
      2005, 44 out of 68 patients treated by arthroscopic rotator cuff repair had been
      reviewed with a mean post-operation time of 12 months. Of the 44 patients, 40
      were available for follow-up, with a mean period of 20.6 (12 - 40) months. The
      mean age was 56 (30 - 81) years. According to Gerber classification, there were 8
      partial tears, 27 small tears and 5 massive tears. No irreparable tear was
      included in this series. All tears were repaired under the scope, and metal
      suture anchor (Super-Revo, Linvatec) had been used in all patients. ASES score
      (American shoulder & elbow surgeons' score), Constant-Murley score and SST
      (simple shoulder test) questionnaire were adopted before operation and at the
      latest follow-up. RESULTS: The pre-operation and post-operation mean ASES score
      was 72.6 vs. 92.3 (P < 0.001), with the mean VAS score for pain 6.2 vs. 1.8 (P <
      0.001), the mean forward flexion 74.5 degrees vs. 146.0 degrees (P < 0.001), and
      the mean external rotation 27.8 degrees vs. 38.3 degrees (P < 0.01). The
      excellent and good rate for post-operation ASES was 92.5%. The pre-operation and
      post-operation mean Constant-Murley score was 69.6 vs. 90.4 (P < 0.001), with an
      excellent and good rate of 90.0%. CONCLUSIONS: Arthroscopic rotator cuff repair
      is a successful treatment for rotator cuff tear. By the use of suture anchors,
      scope surgery shares the advantages of minimal morbidity, quick functional
      recovery and protection of deltoid muscle. With appropriate indication control,
      descent surgical skill and intense postoperative rehab, gratifying outcome can
      usually be anticipated.

PMID- 16635370
TI  - [Arthroscopic treatment of tibial intercondylar eminence avulsion fractures using
      no absorbable suture fixation].
AB  - OBJECTIVE: To study the surgical skill and the clinical outcomes of arthroscopic
      treatment of tibial intercondylar eminence avulsion fractures using no absorbable
      suture fixation. METHODS: A total of 30 cases with avulsion fractures of the
      tibial intercondylar eminence were treated with no absorbable suture fixation
      from January 2001 to December 2004. All procedures were performed
      arthroscopically by the same surgeons. There were 8 cases of type II, 17 type
      III, 5 type IV based on the Meyers and McKeever classification and 26 cases were
      fresh fracture. The procedure was completed with the assistance from No. 18 spine
      needle and Kirschner wire (O2.0 mm and O1.0 mm) and director drill guide.
      Postoperative immobilization was not required. RESULTS: All patients were
      followed up for 3 to 24 months, average (15.0 +/- 4.7) months. Subjective results
      of all cases were uniformly excellent. The mean Lysholm score was 98.4 in 18
      cases of fresh fracture, and 89.8 in 4 cases of old fracture. Mean KT2000 side-to
      side difference was normal in all case. CONCLUSIONS: The technique is simple,
      safe, reproducible, minimal invasion and effective; postoperative immobilization
      is not required; knee joint function is excellent.

PMID- 16635371
TI  - [Arthroscopic treatment of the giant cell tumor of tendon sheath in knee joint].
AB  - OBJECTIVE: To explore the technique of diagnosis and treatment of intra-articular
      giant cell tumor of tendon sheath (GCTTS) in knee joint, and to evaluate its
      clinical results. METHODS: Twelve patients with GCTTS treated during 15 years
      were reviewed. Nine cases were misdiagnosed with meniscus injury (6 cases) and
      chronic synovitis (3 cases) before operation, only 3 cases were confirmed the
      diagnosis of GCTTS by MRI. Complete tumorectomy under arthroscope was performed
      on all 12 cases. RESULTS: The results of clinical and radiographic followed-up of
      9 patients for 1 to 10 years after operation was satisfactory. Clinical symptoms
      disappeared, range of motion and X-ray findings were normal. There was no
      recurrent case found. CONCLUSIONS: Arthroscopic removal of GCTTS is an effective
      treatment. Tumor wide resection and debriding the channel which tumor passed
      through are the key point to prevent the recurrence after operation.

PMID- 16635372
TI  - [Percutaneous fixation of pelvic ring disruptions].
AB  - OBJECTIVE: To introduce the operation indication, operation fashion, operation
      time, mainipulation point, and treatment effect of pelvic ring disruptions with
      percutaneous fixation. METHODS: Fifty-eight patients with pelvic ring disruptions
      were treated with sacroiliac screws, pubic ramus screws or pubic tubercle screws
      and iliac wing screws, and the effects was evaluated. RESULTS: Among the 58
      patients, the result of reductions in 52 cases was satisfied, 6 cases was
      dissatisfied; fracture point in 57 cases was healed up, 1 case disconnect; vessel
      and nerve was not injured in 56 cases, S(1) nerve root was injured in 2 case,
      bequeathing anaesthesia of lower limbs and saddle area. CONCLUSIONS: The
      technique with percutaneous fixations is minitraumatic and reliable to fix the
      pelvic ring disruptions with little bleeding. These percutaneous techniques have
      a good outlook. Bone tractions with big weight before operation make for
      reductions in operation.

PMID- 16635373
TI  - [Research on the systematic inflammatory response syndrome after femoral
      intramedullary nail].
AB  - OBJECTIVE: To investigate the rate of systemic inflammatory response syndrome
      (SIRS) among patients treated by intramedullary nail (IMN) for femoral shaft
      fracture right after the operation, the effect of femoral nailing on SIRS and
      sought to differentiate any differences between reamed and unreamed IMN. METHODS:
      Three hundred and twenty-four patients presenting with acute femoral fractured
      from April 1997 to April 2005, divided into 2 group depending on ISS. Group 1 had
      179 patients (ISS < 16, AIS < 2) including 64 reamed cases and 115 unreamed
      cases; group 2 had 145 patients (ISS >or= 16, AIS >or= 2) including 51 reamed
      patients and 94 unreamed. All patients were treated by close reduction and
      intramedullary nail for fixation. The heart rate, breath rate, temperatures were
      recorded every 6 h before and after operation. If any of the life sign was above
      normal, then venous blood samples were taken at once to make sure whether SIRS
      occurred or not. All data were crosstabs analysis by SPSS 10.0. RESULTS: One
      hundred and twenty-four patients suffered from SIRS postoperation. In group 1, 24
      reamed and 37 unreamed, in group 2, 27 reamed and 36 unreamed. Among those SIRS,
      119 cases healed evenly and 5 patients developed further complication. Between
      reamed and unreamed patients both in group 1 and group 2, there was no
      significant difference found. The Chi-Square value were 0.159 and 2.885
      respectively, total value was 3.467, which P was 0.325, 0.089 and 0.471, all
      greater than 0.05. CONCLUSIONS: Although SIRS will result from IMN, there is no
      significant different effect on the rate of SIRS found between reamed and
      unreamed nail in both group.

PMID- 16635374
TI  - [The rule of proliferation after sciatic injury of rats: immunohistological
      observation].
AB  - OBJECTIVE: To describe the rule of the schwann cell proliferation after
      peripheral nerve injury in detail and to discover the effect of neuroanastomosis.
      METHODS: The model of rat sciatic injury was made, with neuroanastomosis on the
      left side and right side untreated. Then draw the materials 24, 48 h, 4, 7, 14,
      21 d after surgery. And immunohistological stain counted the schwann cell per
      view with Qwin software of Leica Ltd. RESULTS: The number of schwann cell
      increased obviously 4 d after surgery and reached the peak in 7 d. Then it fell
      down and the neuroanastomosis group changed slower and fibroblast hyperplasia in
      the untreated. CONCLUSIONS: The axon support is essential for the schwann cell.
      The precise rule is help for study on neurotrophic factor.

PMID- 16635375
TI  - [Experiment on induction of fibroblasts on 3-D cell-foam structures to express
      osteoblastic phenotype and its mechanism].
AB  - OBJECTIVE: To study the feasibility of osteogenic phenotype expression by human
      skin fibroblasts induced in polyglycolic acid (PGA) foams and the effect of tumor
      necrosis factor-alpha (TNF-alpha) on the expression of bone morphogenetic protein
      (BMP) receptors. METHODS: The fibroblasts were isolated, purified from human
      skin. (1) Fibroblasts were seeded onto PGA foams. The cell-PGA complexes were
      cultured in RCCS for 6 weeks, in the media of TNF-alpha (50 U/ml) and BMP-2 (0.1
      microg/ml). 1 d, 3 and 6 weeks later, cells and extracellular matrix were
      investigated by electron microscopic and histochemistry observation respectively.
      Secretion of osteogenic markers were analyzed by biochemical methods. (2)
      Fibroblasts were seeded on the glass fragments or culture flasks and treated with
      TNF-alpha (50 U/ml) in different usage (one-time, all-time). The RT-PCR method
      and the immunohistochemistry fluorescence staining were used to examine the
      influence of TNF-alpha on the mRNA expression and the protein expression of the
      type I BMP receptors at 2, 4, 6, 8 d after treatment. RESULTS: Fibroblasts seeded
      on the PGA foams formed 3-dimensional matrix 3 weeks after seeding, which was
      demonstrated as osteo-tissue by tetracycline labeling and ARS staining. Cells
      secreted much more bone-specific alkaline phosphatase (B-AKP) and osteocalcin
      (OCN) into supernatant than the cells that were cultured in the media without TNF
      a and BMP2. Eight days after all-time usage, the TNF-alpha (50 U/ml) increased
      the expression of the mRNA and protein of the type IB BMP receptor. CONCLUSIONS:
      Fibroblasts on 3-D cell-foam structures can express osteoblastic phenotype under
      certain inducing conditions. The numerous fibroblasts in body would be a
      promising resource for cell seeds candidate of tissue- engineered bone. TNF-alpha
      provides the essential condition for BMP2's target effect on fibroblasts, and
      combined use of TNF-alpha and BMP2 is one of the regulating factors.

PMID- 16635376
TI  - [Influences of decellularization processes on immunogenicity of chemically
      acellular nerve allografts].
AB  - OBJECTIVE: To investigate the relationship between immunogenicity and
      decellularization processes of chemically acellular nerve allografts. METHODS:
      Adult Sprague Dawley rats were used as nerve donors and adult male Wistar rats
      used as nerve recipient hosts. 25 mm nerve segments were excised from SD rats'
      sciatic nerves. The nerve segments were decellularized via an improved chemical
      decelluarization treatment as follows: (1) nerve segments were rinsed with cold
      sterile Ringer's solution; (2) stabilized by pinning the ends to a thin plastic
      support, and submerged in 4% Triton-100 solution 12 h; (3) soaked into 3% sodium
      deoxycholate for 12 h; (4) washed in distilled water for 6 h. The procedures were
      repeated once again. The acellular nerve allografts from SD rats were sterilized
      by gamma irradiation and implanted into Wistar rats subcutanously. The control
      group was implantation of fresh nerve allografts from SD rats. The immunogenicity
      of acellular nerve allograft was tested by immunohistochemical examination of the
      intensity of CD3(+), CD4(+) and CD8(+) cells that infiltrated the allografts.
      Ulnar nerve segments were obtained from forearms of dogs and decellularized
      according to above procedures. According as the decellularization times, The
      ulnar nerve segments were divided into three subgroups: in group I, group II and
      group III, the nerve segments were decellularized repeatedly two, three and four
      cycles respectively. Each ulnar nerve segment was subdivided into five portions
      from proximal to distal end. The degrees of decellularization, demyelination and
      basal lamina integrity of extracellular matrix scaffold were observed with
      microscope and assessed by a score system. The immunohistochemical staining of
      GAG was observed. RESULTS: The intensity of CD3(+), CD4(+) and CD8(+) T cells
      that infiltrated the allografts was greatly lower in acellular nerves than in
      fresh nerves. The mild cell-mediated host-graft immunorejection in acellular
      nerves was observed. On the decellularization procedures, the cells were
      completely extracted from nerves in all groups, but the myelin sheath were
      partially existed, and the GAG was present in the basal membrane of myelin
      sheath. In the score of demyelination, there were no statistical differences
      between groups (P > 0.05). The statistical difference of basal lamina integrity
      scores between group I and group II, group I and group III were significant (P <
      0.05). As increasing the times of process, the degrees of disintegrity of basal
      lamina was significantly enhanced. CONCLUSIONS: Although decellularization
      processes significantly reduce the cell-mediated immunorejection of acellular
      nerve allografts, it can induce mild immunoreaction all the same, the antigen
      that responsible for immunogenicity may be the residual component of GAG in
      myelin sheath.

PMID- 16635383
TI  - [Prophylaxis and treatment of operation-correlated complications in orthotopic
      liver transplantation].
AB  - OBJECTIVE: To investigate the common reasons, prophylaxis and treatment of
      operation-correlated complications in orthotopic liver transplantation (OLT).
      METHODS: Six hundred and forty-seven patients who underwent OLT from Apr 1993 to
      Dec 2004 were enrolled and analyzed retrospectively. RESULTS: There were totally
      39 cases (6.0%, 39/647) of vascular complications including 23 cases (3.6%) of
      hepatic artery complications, 6 cases (0.9%) of portal vein complications and 10
      cases (1.5%) of vena cava complications. All vena cava complications were
      occurred in the patients of non-cavaplasty. The success rate of stent placement
      in treatment of hepatic artery stenosis was 2/2; for patients with hepatic artery
      thrombosis, the success rate of retransplantation was 4/6, that of revasculation
      and balloon dilation were 3/7 and 2/7 respectively. Stent placement can treat
      both anastomotic strictures and venae cavae stricture with the cure rate of 3/3
      and 10/10 respectively. There were 34 cases of biliary complications, in which 27
      cases were in patients with T tube, and 7 cases in without T tube. The incidence
      of biliary leak and biliary infection was significantly different between these
      two groups. CONCLUSIONS: The modified piggyback (cavaplasty) technique could
      prevent the incidence of venae cavae complications effectively. Stent placement
      is an effective way to treat vascular stenosis. And retransplantation should be
      performed in early hepatic artery thrombosis. It is important to protect the
      blood supply of biliary system, and choledochostomy without T tube is the first
      choice for biliary reconstruction.

PMID- 16635384
TI  - [Liver retransplantation: report of 80 cases].
AB  - OBJECTIVE: To sum up the clinical experience of liver retransplantation. METHODS:
      The clinical data of patients receiving liver retransplantation in our department
      between Jan. 1999 and July 2005 were retrospectively analyzed, the cause of
      retransplantation, timing of retransplantation, technical considerations and the
      causes of death. RESULTS: The most common causes of hepatic graft loss and
      subsequent retransplantation are biliary complications (45.0%). Patients who
      received retransplantation more than 30 days after their initial transplant fared
      better than those who received retransplants between 8 and 30 days after
      receiving their first one (intraoperative mortality rates 19.6% versus 70.0%).
      The development of sepsis (54.5%) and multiorgan failure (18.2%) accounts for the
      majority of deaths in retransplanted patients. CONCLUSIONS: Proper indication and
      optimum operation time, surgical procedure, perioperative monitoring and proper
      treatment post operation contribute to the increase of the survival rate of the
      patients receiving liver retransplantation.

PMID- 16635386
TI  - [Combined total hepatectomy, orthotopic liver transplantation and
      pancreatoduodenectomy for unresectable hilar bile duct carcinoma].
AB  - OBJECTIVE: To explore the feasibility and outcome of combined hepatectomy,
      orthotopic liver transplantation and Whipple's pancreatoduodenectomy for radical
      excision of cholangiocarcinoma. METHODS: A 35-year-old female patient with
      unresectable cholangiocarcinoma underwent curative radical operation, which
      includes hepatectomy, orthotopic liver transplantation and
      pancreaticoduodenectomy of hilar bile duct carcinoma; immunosuppression followed
      an induction protocol with FK506 and steroids. Lamivudine and HBIg were used to
      prevent hepatitis B virus from infection again. RESULTS: Pathologic examination
      revealed low differentiated cholangiocarcinoma and immunohistochemistry stains
      demonstrated positive expression of cytokeratin 9 and 17, carcinoembryonic
      antigen and the hepatocyte protein was negative. Neither the margins of resection
      nor the periductal lymph nodes were involved. The liver showed evidence of
      cholestasis and metastasis nod. The patient was hospitalized 32 days and came
      back to the previous work. He has been followed up for more than 14 months up to
      now and is currently alive without any evidence of recurrent cancer. CONCLUSIONS:
      For some selected unresectable Klatskin's tumors, combined hepatectomy,
      pancreatoduodenectomy and orthotopic liver transplantation was justified. The
      radical methods maybe provide long-time survival and curative effect.
      Nevertheless, because of possible tumor recurrence and ethical controversy, the
      combined hepatectomy, pancreatoduodenectomy and orthotopic liver transplantation
      procedure has to be applied only with caution and indications.

PMID- 16635387
TI  - [Histochemical and ultrastructure study of bile cast in liver transplantation
      patients].
AB  - OBJECTIVE: To investigate the histological components and solubility of the bile
      cast, and to study the pathological course of bile cast formation. METHODS: HE
      staining, bilirubin staining (Gmelin reaction), Masson's staining, alcian blue
      staining and fibrin staining (weigert's) were performed on the formalin-fixed
      paraffin-embedded section of the bile cast. Ultrastructure was examined under the
      scanning electron microscope. Solubility test was also conducted using
      chymotrypsin, heparin, trypsin solution, HCl and NaOH solution to dissolve the
      bile-cast. RESULTS: The major components of the bile-cast were bilirubin crystals
      and collagen fibers. Between the mass of collagen fibers there was certain blood
      vessel structure. Necrosis bile duct structure was not found in the cast. Under
      the scanning electron microscope, four kinds of crystal morphologies were viewed.
      There were some mucoid mass and necrosis defluvium epithelial cells in the bile
      cast. Solubility test showed that the bile cast could be partial dissolved in
      NaOH solution (pH = 12.5). No dissolution was found in HCl solution (pH = 5.0),
      chymotrypsin solution, heparin and trypsin solution. CONCLUSIONS: Collagen fibers
      work as framework in the bile cast with bilirubin crystal filling between the
      framework. The emergence of fibroblast and blood vessels indicated the formation
      of bile cast might be the course of exudation and organization due to bile duct
      epithelium damage. Bile cast could be partially dissolved in alkaline solution,
      but could not be dissolved in acid solution, or in chymotrypsin, heparin and
      trypsin solutions.

PMID- 16635388
TI  - [The protective effect of heat shock protein 72 by Doxorubicin in cold ischemia
      reperfusion injury of the rat liver].
AB  - OBJECTIVE: To observe induction of heat shock reaction by pretreatment of
      Doxorubicin (DXR) in long-term cold preservation-reperfusion injury of the rat
      liver. METHODS: The rats were administered intravenously by DXR at a dose of 1
      mg/kg body weight in DXR group and by saline in control group. After 48 hours,
      the rat liver was perfused by using cold University of Wisconsin (UW) solutions
      and was preserved in UW solution at 4 degrees C for 48 hours. Recipient liver was
      perfused for 1 and 3 hours after orthotopic liver transplantation. Tumor necrosis
      factor-alpha (TNF-alpha) mRNA, cytokine-induced neutrophil chemoattractant (CINC)
      mRNA, macrophage inflammatory protein (MIP-2) mRNA was measured by RT-PCR and
      heat shock protein 72 (HSP72), nuclear factor-kappaB (NF-kappaB) by Western blot.
      The serum levels of TNF-alpha, CINC, MIP-2 by ELISA and AST were measured. The
      survival rate of 7 days was observed. RESULTS: The expression of TNF-alpha mRNA,
      CINC mRNA and MIP-2 mRNA was stronger in control group than in DXR group. HSP72
      was expressed in SA group but not in control group and oppositely NF-kappaB was
      expressed in control group but not in DXR group. Serum AST, TNF-alpha, CINC and
      MIP-2 concentrations were significantly lower in DXR group than in control group
      (P < 0.05). The survival rate of 7 days was significantly higher in DXR group
      than in control group (50% vs. 0%, P < 0.05). CONCLUSIONS: These data suggested
      that long-term cold ischemia-reperfusion injury was attenuated in liver graft
      with pretreatment of DXR. The induction of HSP72 may offer protection to
      hepatocytes by restraining the activation of NF-kappaB and inflammation.

PMID- 16635390
TI  - [Clinical degree of the superior mesenteric vein involvement with the surgery in
      the pancreas uncinate process carcinoma].
AB  - OBJECTIVE: To create the clinical degree of the superior mesenteric vein (SMV)
      involvement in pancreas uncinate process carcinoma (PUPC) and its clinical
      significance to be discussed. METHODS: According to the contiguous relationship
      between the SMV and the PUPC, the clinical degree of SMV involvement in PUPC are
      as followings four grades, 1 grade, the grade of clear boundary. 2 grade, the
      grade of fuzzy boundary. 3 grade, the grade of dissolved boundary. 4 grade, the
      grade of SMV infringed. The coherence between the type under the CT scan (Tx) and
      the type under the inoperative judgement (Sx) were analyzed with Kappa-test.
      RESULTS: There is a significant difference between the grade of SMV involvement
      and the surgery. The resection rate is 100% in 1st grade, 97.4% in 2nd grade,
      65.8% in 3rd grade and 21.7% in 4th grade. There is coherent in the degree
      judgement between the CT scan and the inoperative inspection (U = 15.96, P <
      0.01). CONCLUSIONS: There is clinical significance to establish the degree of SMV
      involvement in PUPC. It is helpful for clinician to accurately know its anatomic
      characteristic and decide more reasonable surgical strategy.

PMID- 16635391
TI  - [Diagnosis and treatment of hepatic focal nodular hyperplasia: report of 114
      cases].
AB  - OBJECTIVE: To explore the diagnosis and treatment of the hepatic focal nodular
      hyperplasia (FNH). METHODS: The clinical data of 114 patients with FNH proved by
      the pathology were analyzed retrospectively. RESULTS: FNH occurs as a single node
      in 98.1%, ranging from 0.9 cm to 15.0 cm in diameter [average, (4.2 +/- 2.2) cm],
      only 2 patients had more than one FNH nodules. 86.0% of patients with FNH were
      below 50 years old. 89.5% of patients were asymptomatic. AFP was negative in all
      patients. Hepatitis B was negative in 4.4% (5/114) of patients. Of these
      patients, 50 lesions were in the left lobe, 50 in the right lobe, 6 in the mid
      lobe, and 8 in the caudate lobe. A big central artery was found in 3.5% (4/113)
      of the lesion in patients by color Doppler ultrasound. CT scan showed transient
      immediate enhancement in 94.3% (66/70) of patients, with central scar in 10
      cases. The demonstration of a central scar in the lesion was very helpful for the
      diagnosis of FNH. MRI demonstrated early vigorous enhancement in 91.8% (56/61) of
      patients. It is strong enhancement on arterial phase and slight or obvious
      enhancement on portal venous phase and slightly delayed enhancement of the
      central scars in FNH. Eleven cases showed central scar. MRI was more helpful for
      the diagnosis of FNH using liver specific contrast agents: superparamagnetic iron
      oxide (SPIO). All patients underwent focus resection, and there was no mortality
      and severe complication. CONCLUSION: FNH shows some typical clinical and imaging
      features. We could improve the correct diagnosis rate by comprehensively
      analyzing the clinical and imaging materials.

PMID- 16635392
TI  - [To inquiry into clinical-pathological factors influencing cytological accuracy
      of pancreatic head lesions].
AB  - OBJECTIVE: To inquiry into clinical-pathological factors influencing cytological
      accuracy of pancreatic head lesions. METHODS: Cytology was retrospectively
      evaluated in 94 inpatients with a mass in head of pancreas existing with chronic
      pancreatitis in the past decade, the results of cytology were compared with
      clinical pathology or clinical follow-up to estimate the value and accuracy of
      cytology in detecting pancreatic cancer. Pancreatic clinical-pathology includes
      size of mass and component of mass which was composed of cancerous mode of
      development including shape of conglomeration, nest and pervasion, and pancreatic
      ductal epithelium inside the vicinity of 1 cm around the mass. Pancreatic ductal
      epithelium were divided into PanIN1, PanIN2 and PanIN3 three types according to
      classified criterion of pancreatic intraepithelial neoplasia (PanIN). RESULT:
      Forty-six patients were pathologically diagnosed as pancreatic cancer and five
      patients as chronic pancreatitis, accordingly, 29 malignant, 5 suspicious, 10
      atypical hyperplasia among of them 5 malignant, 3 hyperplastic ductal epithelium,
      1 nondiagnostic results due to interfered by blood and 3 insufficient specimens.
      43 patients were clinically diagnosed as chronic pancreatitis. Cytologic
      evaluation of pancreatic cancer has an 84.2% accuracy less than or equal to 2.5
      cm and 71.9% larger than 2.5 cm. Shape of conglomeration, and nest have more
      accurate than pervasion in cytological diagnosis. CONCLUSIONS: Cancerous mode of
      development is a vital factor influencing accuracy of cytology, cytological
      estimation of atypical hyperplasia and is still waiting for further
      investigation.

PMID- 16635393
TI  - [Common failure reasons and improvement ways in treatment of gallstones by
      choledochoscope in operation].
AB  - OBJECTIVE: To analyze common problems, failing causes and improvement ways for
      curing gallstones by choledochoscope in operation. METHOD: To analyze a case
      group of 762 individual patients who had undergone choledochoscope operations in
      the period of Jan, 1995 approximately Sep, 2005. RESULTS: 136 cases are found
      with residual stones in the bile duct after the operations. Residual stone rate
      amounts to 17.8%. 55 patients are known that bile duct stones could not be remove
      completely during operations. 81 patients are proved that stones still remain in
      their bile ducts by T-tube cholangiography and choledochoscope after operations.
      Among them, 29 patients complicate with narrow in intrahepatic bile ducts and
      debouch of bile ducts, 39 patients complicate with stones of intrahepatic bile
      and variation of bile duct, 13 patients complicate with stones and narrow at the
      inferior segment of choledochus. CONCLUSIONS: It is important to pay attention
      for bile duct variation and debouch of affection bile duct or inferior segment of
      choledochus stenosis. B-ultrasound is useful to reduce residual stones in
      operations. The surgeon should check different lengths of the duct methodically,
      and use the endoscope to explore the bile duct in order not to omit any stones.

PMID- 16635394
TI  - [Surgical therapy of tumor of body and tail of pancreas: report of 117 cases].
AB  - OBJECTIVE: To explore diagnosis and surgery therapy and factors influencing the
      prognosis of tumor of body and tail of the pancreas. METHODS: The clinical data
      of 117 cases of tumor of tail and body of pancreas who underwent operation were
      analysed. RESULTS: Imaging and tumor marker detection can give exact diagnosis to
      cases with tumors of body and tail of pancreas. The medial survival time of
      radical resection, palliative resection and exploratory laparotomy were 18, 8 and
      3.5 months. CONCLUSIONS: Atypical signs should be noticed, combined imaging and
      serum detection can diagnose the cases exactly, radical resection is the unique
      method for long survival, the diameter of the tumor and degree of infiltration to
      major vessels and organs is important.

PMID- 16635397
TI  - [Comparison of wound healing after pancreaticojejunostomy with three anastomotic
      methods in piglets].
AB  - OBJECTIVE: To evaluate wound healing after pancreaticojejunostomy of three
      anastomotic methods. METHODS: Fifty-four domestic piglets were divided into three
      groups according to the types of anastomoses: group of end-to-end
      pancreaticojejunal invagination (EE group), group of binding
      pancreaticojejunostomy (BP group) and group of inkwell pancreaticojejunostomy (IP
      group). Bursting pressure, breaking strength and histopathological findings of
      anastomosis were assessed on operative day and on the 5th and 10th day after
      operation. RESULTS: Bursting pressure was (67+/-8) mm Hg, (96+/-11) mm Hg and
      (131+/-9) mm Hg in EE group on day 0, 5 and 10; and (140+/-8) mm Hg, (179+/-10)
      mm Hg and (269+/-13) mm Hg in BP group; and (102+/-10) mm Hg, (171+/-18) mm Hg
      and (254+/-24) mm Hg in IP group. Compare to EE group, bursting pressure of BP
      group and IP group were all increased with significant differences (P<0.05).
      Another significant difference was observed between BP group and IP group after
      anastomoses on operative day. Breaking strength was (4.6+/-0.6) N, (5.8+/-0.5) N
      and (7.1+/-0.6) N in EE group on 0 d, 5 d and 10 d; and (4.5+/-0.4) N, (6.6+/
      0.4) N and (10.0+/-0.6) N in BP group; and (4.6+/-0.3) N, (6.5+/-0.4) N and
      (9.1+/-0.9) N in IP group. A similar value of anastomoses was shown in BP group
      and IP group on day 0, day 5 and day 10, but significant increase was
      demonstrated compared to EE group on day 5 and 10. Anastomotic site was well
      repaired by connective tissue and the cut surface of pancreatic stump was covered
      by mucosal epithelium in BP group and IP group on day 10, but the cut surface was
      incompletely repaired by granulation tissue and no regeneration of the epithelium
      was found in EE group. CONCLUSIONS: Wound healing of binding
      pancreaticojejunostomy and inkwell pancreaticojejunostomy is more rapid and
      better than end-to-end pancreaticojejunal invagination, but breaking strength of
      inkwell pancreaticojejunostomy is weaker than binding pancreaticojejunostomy.

PMID- 16635398
TI  - [The relationship between frameshift mutations of transforming growth factor-beta
      type II receptor, insulin growth factor II receptor, bcl-2 associated X protein,
      E2F4 and microsatellite instability in gastric carcinoma].
AB  - OBJECTIVE: To determine the microsatellite instability in gastric carcinomas,
      examine the frameshift mutations of transforming growth factor-beta type II
      receptor (TGFbetaRII), insulin growth factor II receptor (IGFIIR), bcl-2
      associated X protein (BAX) and E2F4, and investigate whether or how alterations
      of the TGFbetaRII, IGFIIR, BAX and E2F4 gene are associated with MSI in gastric
      cancer. METHODS: Formalin-fixed, paraffin-embedded gastrectomy specimens and
      matching normal tissues of 65 cases of gastric carcinomas were retrieved from
      shanghai Ruijin Hospital and Shanghai East Hospital. DNA was extracted from
      tissue sections using phenol chloral isoamyl alcohol. Sections with no more than
      50% of tumor cell areas were isolated by microdissection. DNA was amplified by
      PCR-based single strand conformation polymorphism (SSCP) for microsatellite
      analysis and was sequenced directly. Frameshift mutations in the coding regions,
      repetitive mononucleotide tracts of (A)10 for TGFbetaRII, (G)8 for IGFIIR, (G)8
      for BAX, and trinucleotide repeats of (AGC)13 for transcription factors E2F4 were
      detected using PCR. Tumors were classified as being microsatellite stable (MSS)
      or having a low frequency of MSI (MSI-L, one of markers different in the tumor)
      or a high frequency of MSI (MSI-H, two or more of markers different). RESULTS:
      Eleven cases (18.0%) showed MSI-L, 12 (19.7%) showed MSI-H and 38 (62.3%) cases
      showed MSS. The mutation rates of TGFbetaRII, IGFIIR, BAX and E2F4 gene were
      19.7%, 4.9%, 6.6% and 16.4% respectively. Among the 12 MSI-H gastric cancers,
      there were 10 TGFbetaRII mutations, 3 IGFIIR mutations, 4 BAX mutations and 10
      E2F4 gene mutations. The alterations in the repeats of the related genes
      presented polymorphisms. Associations of MSI-H status and mutations of the 4
      genes were highly significant (P < 0.01, respectively). No repeat tracts
      mutations in TGFbetaRII, IGFIIR, BAX and E2F4 gene were found in MSS tumors.
      CONCLUSIONS: The repeat coding regions within TGFbetaRII, IGFIIR, BAX and E2F4
      gene are the targets of microsatellite instability. Frameshift mutations of the 4
      genes play an important role in the development and progression of gastric
      cancers with microsatellite instability.

PMID- 16635399
TI  - [The effect of combination of glycine and methylprednisolone on Kupffer cells of
      liver after hemorrhagic shock in rats].
AB  - OBJECTIVE: To investigate the effect of combination of glycine and
      methylprednisolone (MP) on Kupffer cells in liver of rats suffered from
      hemorrhagic shock. METHODS: Fifty Wistar rats were bled to establish the shock
      model and subsequently resuscitated with shed blood and normal saline. Just prior
      to resuscitation, the rats were randomly assigned to 5 groups: sham group, shock
      group, shock + glycine group, shock + MP group and shock + glycine + MP group.
      The intracellular calcium concentration and the level of tumor necrosis factor
      alpha (TNF alpha) in the culture medium of Kupffer cells were determined after
      stimulation with different concentrations (1, 10, 100 and 1000 ng/ml) of
      lipopolysaccharide (LPS). RESULTS: Concentration of intracellular calcium and
      production of TNF-alpha by isolated Kupffer cells stimulated by LPS were elevated
      significantly in the rats with hemorrhagic shock, which were totally prevented by
      glycine + MP compared with other groups (P < 0.005). CONCLUSIONS: The combination
      of glycine and MP prevents the increase of intracellular calcium of Kupffer cell,
      suppress Kupffer cell activation, decrease the production of TNF-alpha of Kupffer
      cell and block systemic inflammatory responses more effectively than single
      administer of glycine or MP.

PMID- 16635404
TI  - New approach for new target: adaptive servo-ventilation on Cheyne-Stokes
      respiration in congestive heart failure.

PMID- 16635405
TI  - Efficacy of adaptive servoventilation in patients with congestive heart failure
      and Cheyne-Stokes respiration.
AB  - BACKGROUND: Congestive heart failure (CHF) is associated with Cheyne-Stokes
      respiration (CSR), which may hasten CHF. Adaptive servoventilation (ASV) is a
      novel method of ventilatory support designed for removal of CSF in CHF patients.
      This study compares the efficacy of ASV in patients with CHF and CSR with the
      efficacy of oxygen therapy. METHODS: Fourteen patients with CHF and CSR were
      recruited. During sleep, nasal oxygen therapy and ASV treatment were each
      performed for two weeks. Comparison before and after each treatment was made for
      the following items: a) parameters of sleep respiration, sleep structure and
      quality; b) left ventricle ejection fraction (LVEF) and 6-minute walk distance.
      RESULTS: Compared with the baseline levels of apnoea hypopnoea index of 34.5 +/-
      6.1 before treatment, the apnoea hypopnoea index significantly decreased
      following oxygen therapy to 27.8 +/- 8.2, P < 0.05 and further reduced following
      ASV treatment to 6.5 +/- 0.8, P < 0.01. The minimal pulse oxygen saturation
      markedly increased following oxygen therapy from a baseline of (84.3 +/- 2.6)% to
      (88.6 +/- 3.7)%, P < 0.05 and further increased following ASV treatment (92.1 +/-
      4.9)%, P < 0.01. Stages I + II sleep as percentage of total sleep time decreased
      from (81.9 +/- 7.1)% to (78.4 +/- 6.7)% following oxygen therapy and further to
      (72.4 +/- 5.0)% following ASV treatment. Stages III + IV sleep as percentage of
      total sleep time decreased from (8.4 +/- 5.5)% to (6.0 +/- 3.0)% following oxygen
      therapy and but increased to (11.9 +/- 5.4)% following ASV treatment. The arousal
      index of 30.4 +/- 8.1 before treatment significantly decreased following oxygen
      therapy to 25.6 +/- 5.7, P < 0.05 and further declined following ASV treatment to
      18.2 +/- 6.1, P < 0.01. No significant difference was shown in above percentages
      between day 14 of oxygen therapy and before treatment (P > 0.05). LVEF was
      significantly higher on day 14 of ASV treatment (37.2 +/- 4.1)% than on day 14 of
      oxygen therapy (33.2 +/- 5.1)% and before treatment (30.2 +/- 4.6)% (all P <
      0.05). Six-minute walk distance was the shortest before treatment (226 +/- 28) m,
      longer on day 14 of oxygen therapy (289 +/- 26) m, and the longest on day 14 of
      ASV treatment (341 +/- 27) m (all P < 0.01). CONCLUSION: ASV treatment is of
      better efficacy and greater clinical significance in improvement of CHF by
      eliminating CSR than oxygen therapy.

PMID- 16635406
TI  - The role of serum leptin and tumor necrosis factor-alpha in malnutrition of male
      chronic obstructive pulmonary disease patients.
AB  - BACKGROUND: Leptin is a protein mainly secreted by adipocytes, and the major
      function of leptin was its role in body weight regulation. It is suggested that
      increased levels of circulating leptin may contribute to anorexia in pathologic
      conditions including chronic obstructive pulmonary disease (COPD). Recent studies
      have provided evidence for a link between leptin and proinflammatory cytokines
      such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the
      role of serum leptin in the malnutrition of COPD patients, and to observe the
      changes of serum leptin levels during acute exacerbation, also to investigate
      relationship between leptin and TNF-alpha. METHODS: Seventy-two COPD patients and
      34 control subjects participated in this study. Seventy-two COPD patients were
      divided into 3 groups: group COPD IA (patients without malnutrition during acute
      exacerbation, n = 25), group COPD IB (patients without malnutrition during stable
      disease, n = 29), group COPD II (patients with malnutrition during stable
      disease, n = 18). To eliminate the effect of sex differences, all patients and
      controls were male. Body mass index (BMI), percent ideal body weight (IBW%),
      triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper
      arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum
      prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes
      count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration
      pressure (MIP) and maximal expiration pressure (MEP) were measured in all
      participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels
      were measured by ELISA. The between group difference and correlation of these
      parameters were analyzed. RESULTS: Serum leptin levels were significantly lower
      in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67)
      ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no
      statistically significant difference in serum leptin levels between group COPD IA
      [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls
      [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in
      serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD
      IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was
      no significant correlation between leptin and TNF-alpha in any group.
      CONCLUSIONS: Leptin was not involved in anorexia and weight loss of COPD
      patients. There was no statistically significant difference in serum leptin
      levels between COPD patients during stable stage and acute exacerbation, and
      there was no significant correlation between TNF-alpha and leptin during the
      regulation of the energy balance in COPD patients.

PMID- 16635407
TI  - The role of 11C-choline positron emission tomography-computed tomography and
      videomediastinoscopy in the evaluation of diseases of middle mediastinum.
AB  - BACKGROUND: Middle mediastinal masses comprise a wide variety of tumors but may
      also reflect lymphadenopathy, and thus remain an interesting diagnostic
      challenge. We performed positron emission tomography (PET) of mediastinal masses
      in order to evaluate the ability of PET to predict the malignancy of these
      tumors. We compared histologic findings, videomediastinoscopy, computed
      tomography (CT), and PET-CT in patients with mediastinal disease. METHODS: Thirty
      two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all
      studies were performed within four weeks in each patient. (11)C-choline as a PET
      tracer was used to visualize masses. PET data were evaluated using the
      standardized uptake value (SUV) and were compared with pathologic data. RESULTS:
      There were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the
      patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients,
      tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata
      without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was
      revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung
      cancer, and one was negative (the pathological diagnosis was reactive
      hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT,
      PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32)
      respectively. The diagnostic accuracy of videomediastinoscopy was superior to
      that of PET-CT (chi(2) = 11.130, P < 0.001). The SUVs were similar among these
      diseases. On the other hand, if the diagnostic classification was benign vs
      malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53%
      (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of
      videomediastinoscopy was superior to that of PET-CT (chi(2) = 22.042, P < 0.001).
      The SUV of malignant lesions (6.9, 3.2 - 9.8; n = 11) appeared to be higher than
      that of benign lesions (4.9, 2.9 - 8.3; n = 21), however, this difference was not
      statistically significant (P = 0.054). CONCLUSIONS: To diagnose lesions located
      in the middle mediastinum, videomediastinoscopy possesses the highest diagnostic
      accuracy, and therefore remains the gold standard. PET-CT is valuable for
      differential diagnosis of benign vs malignant lesions, CT alone or PET alone
      (SUV) may provide misdiagnosis in a substantial proportion of patients with
      mediastinal masses.

PMID- 16635409
TI  - Effects of angiotensin converting enzyme inhibitor, angiotensin II type I
      receptor blocker and their combination on postinfarcted ventricular remodeling in
      rats.
AB  - BACKGROUND: Transforming growth factor (TGF) beta(1)-Smads signal plays an
      important role in cardiac remodeling following myocardial infarction (MI). In
      addition, both angiotensin converting enzyme inhibitor (ACEI) and angiotensin II
      type I receptor blocker (ARB) can effectively prevent left ventricular
      remodeling. The current study focused on whether the combination of ACEI and ARB
      is more beneficial for preventing ventricular remodeling and whether Smad
      proteins mediate this beneficial effect. METHODS: MI was induced by ligating the
      left anterior descending coronary artery in rats. Twenty-four hours after
      ligation, the survived rats were randomly divided into five groups and treated
      for 8 weeks: placebo group, ACEI group (benazepril 10 mg.kg(-1).d(-1)), ARB group
      (irbesartan 50 mg.kg(-1).d(-1)), ACEI + ARB group (benazepril 10 mg.kg(-1).d(-1)
      + irbesartan 50 mg.kg(-1).d(-1)) and control group (sham-operated rats). After 8
      weeks, we examined the following indexes: the ratio of ventricular weight to body
      weight (VW/BW), left ventricular end diastolic dimension (LVDd), ejection
      fraction (EF), fractional shortening (FS), ratio of E-wave to A-wave velocity,
      collagen of noninfarcted zone, the mRNA expression of TGFbeta(1), Smad 2, and
      Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad
      3 in noninfarcted zone by Western blot. RESULTS: VW/BW significantly increased in
      the placebo groups compared with that in the control group (P < 0.01). This
      increase was limited in ACEI, ARB, and combined groups (P < 0.01 compared with
      placebo group). There was no significant difference among the three actively
      treated groups. Collagen was increased in placebo group (5.68 +/- 0.5)% compared
      with that in control group (P < 0.01). ACEI, ARB and combined treatment
      attenuated this increase of collagen [(4.3 +/- 0.5)%, (3.5 +/- 0.5)%, (3.2 +/-
      0.4)%] in comparison with that in placebo group (P < 0.01 respectively). Combined
      treatment showed more significant effect on collagen deposition. EF and FS
      significantly decreased, LVDd and E/A significantly increased in placebo group
      compared with that in control group (P < 0.01 respectively). ACEI, ARB and
      combined treatment ameliorated these indexes (P < 0.01 compared with placebo
      group). The mRNA expression of TGFbeta(1), Smad 2, and Smad 3 (0.700 +/- 0.045,
      0.959 +/- 0.037 and 0.850 +/- 0.051) increased in placebo group compared with
      that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the
      increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more
      effective in decreasing TGF beta(1) and Smad mRNA expression than ACEI treatment
      (P < 0.01). The expression of Smad 2 and Smad 3 protein increased in placebo
      group compared with that in control group (P < 0.01). ACEI, ARB and combined
      treatment normalized the increase (P < 0.01). Furthermore, ARB and combined
      treatment proved to be more effective than ACEI alone (P < 0.01). CONCLUSIONS:
      TGFbeta(1)-Smads signal activation is correlated with ventricular remodeling
      following MI. ACEI and ARB treatment prevents ventricular remodeling by
      inhibiting expression of Smad 2 and Smad 3. ARB and combined treatment are more
      effective than ACEI alone.

PMID- 16635408
TI  - Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod
      modulating transcription factors T-bet and GATA-3.
AB  - BACKGROUND: Imiquimod is an imidazoquinoline, which class of compounds are known
      to have antiviral and antitumoural properties. In recent studies, it was shown
      that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the
      production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines
      like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3
      are master Th1 and Th2 regulatory transcription factors. This study investigated
      whether imiquimod treatment inhibited airway inflammation by modulating
      transcription factors T-bet and GATA-3. METHODS: Thirty-six male SD rats were
      randomly divided into a control group, an asthmatic group, and an imiquimod
      group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours
      after the last ovalbumin (OVA) challenge, airway responsiveness was measured and
      changes in airway histology were observed. The concentrations of IL-4, IL-5 and
      IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by
      enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5,
      IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by
      reverse transcription polymerase chain reaction (RT-PCR). The protein expressions
      of T-bet and GATA-3 were measured by Western blot. RESULTS: It was demonstrated
      that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the
      degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines
      and increased Th1 type cytokines mRNA and protein levels; 4) modulated the
      Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production.
      CONCLUSION: Imiquimod treatment inhibits OVA induced airway inflammation by
      modulating key master switches GATA-3 and T-bet that result in committing T
      helper cells to a Th1 phenotype.

PMID- 16635410
TI  - Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal
      mucosal barrier in severe acute pancreatitis in dogs.
AB  - BACKGROUND: One of the major causes of death in severe acute pancreatitis (SAP)
      is severe infection owing to bacterial translocation. Some clinical studies
      suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment
      effect on SAP patients. But the experiment studies on the precise mechanism of
      the effect of EIN were less reported. In this study, we mainly investigated the
      effects of EIN on bacterial translocation in SAP model of dogs. METHODS: SAP was
      induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct
      in healthy hybrid dogs. The SAP dogs were supported with either parenteral
      nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum
      amylase, serum aminotransferase and plasma endotoxin were detected before and
      after pancreatitis induction. On the 7th day after nutrition supports, peritoneal
      fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for
      bacterial culture with standard techniques to observe the incidence of bacterial
      translocation. Pathology changes of pancreas were analyzed by histopathologic
      grading and scoring of the severity of pancreas, and the degree of intestinal
      mucosal damage was assessed by measuring mucosal thickness, villus height, and
      crypt depth of ileum. RESULTS: Compared with PN and EEN, EIN significantly
      decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin,
      and the incidence of bacterial translocation. Furthermore, compared with the
      others, the histology scores of inflammation in pancreas and the ileum injury
      (ileum mocosa thickness, villus height, and crypt depth) were significantly
      alleviated by EIN (P < 0.05). Moreover, concerning liver function, the serum
      levels of alanine aminotransferase, aspartate aminotransferase and albumin were
      ameliorating significantly in the EIN group. CONCLUSION: Our results suggested
      that EIN could maintain the integrity of intestinal mucosal barrier and reducing
      the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more
      effective treatment for SAP dogs.

PMID- 16635411
TI  - Meta-analysis of defibrase in treatment of acute cerebral infarction.
AB  - BACKGROUND: Fibrinogen-depleting agents are promising in the treatment of
      cerebral ischemic disease. They were studied by many trials, and the outcomes
      were different because of different regimens and different doses. In this study,
      we assessed the efficacy and safety of defibrase on acute cerebral infarction in
      China. METHODS: A search using Chinese hospital knowledge database (CHKD) and
      MEDLINE database for randomized controlled trials was carried out. A CHKD (1994
      June 2005) search was performed with the keyword "defibrase", then a second
      search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June
      2005) was performed with the following keywords: [(cerebral ischemia), OR (acute
      cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed
      with RevMan software 4.2. RESULTS: Included were 14 studies comparing the
      efficiency and safety of defibrase with other drugs in the treatment of acute
      cerebral infarction. Patients' records were pooled (total 646 patients;
      defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS)
      before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence
      interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20,
      95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45,
      95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment
      showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level
      after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001.
      CONCLUSIONS: With the given dose and regimen of defibrase in China, defibrase may
      play a role of anticoagulation. It might inhibit the progression of stroke and
      prevent the recurrence of stroke.

PMID- 16635412
TI  - Increasing awareness of recognition of chronic obstructive pulmonary disease.

PMID- 16635413
TI  - Links between allergic rhinitis and asthma.

PMID- 16635414
TI  - Relationship among bacterial colonization, airway inflammation, and
      bronchodilator response in patients with.

PMID- 16635415
TI  - Pulmonary major histocompatibility complex expression pattern is suggestive of
      the characteristics of airway antigen.

PMID- 16635416
TI  - Effect of mycobacteriophage to intracellular mycobacteria in vitro.

PMID- 16635417
TI  - Electrochemotherapy for rat implanted liver tumour.

PMID- 16635418
TI  - Dynamic observation of polypide in semen and blood of rabbits infected with
      Toxoplasma tachyzoites.

PMID- 16635420
TI  - Infections in MS: beneficial or harmful?

PMID- 16635421
TI  - Neuromyelitis optica.
AB  - Neuromyelitis optica (NMO), otherwise known as Devic's disease, is an idiopathic,
      severe, inflammatory disorder that preferentially affects the optic nerves and
      spinal cord. Clinical, laboratory and immunopathological evidence suggests that
      NMO is a humorally mediated disease distinct from MS. A spinal cord lesion
      extending contiguously over three or more vertebral segments is characteristic of
      NMO and, in combination with a cranial magnetic resonance imaging scan that does
      not meet radiological criteria for MS, is over 94% sensitive and 96% specific for
      NMO diagnosis. The serum autoantibody marker, neuromyelitis optica-immunoglobulin
      G (NMO-IgG), appears specific for NMO and suggests that the disease spectrum
      includes cases of recurrent longitudinally extensive transverse myelitis and
      Japanese opticospinal MS. Its target antigen is the water channel aquaporin-4,
      suggesting that NMO may represent a novel autoimmune channelopathy. Relapsing NMO
      has a poor prognosis; therapy, typically with immunosuppression, is necessary as
      early as possible in the disease course to prevent attack-related disability.

PMID- 16635422
TI  - The role of EBV in MS pathogenesis.
AB  - Environmental factors operate on a background of genetic susceptibility in the
      pathogenesis of MS. Human herpesviruses, notably Epstein-Barr virus (EBV), and
      human endogenous retroviruses are factors associated with MS. EBV association is
      found in epidemiological surveys where late EBV infection confers a higher risk
      of MS, and EBV reactivation also appears to be linked to disease activity in
      early MS. MS patients have elevated anti-EBV antibody responses, both in serum
      and cerebrospinal fluid. Molecular mimicry is found between certain EBV and
      myelin epitopes in the cell-mediated immune response. EBV cannot stand alone as a
      causal factor of MS, but is likely to play an indirect role as an activator of
      the underlying disease process.

PMID- 16635423
TI  - Survival and mortality rates among Danes with MS.
AB  - Long-term survival and trends in overall and cause-specific excess mortality
      among people with MS have been studied using the Danish Multiple Sclerosis
      Registry, which contains information about all Danish MS patients since the mid
      20th Century. A total of 4254 deaths among approximately 10,000 people with MS,
      representing more than 200,000 person-years of observation, have been analysed.
      Overall, mortality was almost three times higher and life expectancy 10 years
      less among people with MS than for the general population. However, excess
      mortality has declined significantly since 1950.

PMID- 16635424
TI  - Spinal neurons exhibit a surprising capacity to learn and a hidden vulnerability
      when freed from the brain's control.

PMID- 16635425
TI  - Unraveling molecular markers of biologic therapies in glioma.

PMID- 16635426
TI  - Stroke in cancer patients.
AB  - Cancer patients are at increased risk for stroke from direct and indirect effects
      of their malignancy. Some tumors are at high risk for cerebrovascular
      complications. Certain stroke mechanisms are specific to cancer, such as
      compression and occlusion of cerebral vessels by tumor, coagulopathy predisposing
      to hemorrhage and thrombosis, and treatment-related atherosclerosis. Special
      consideration for these mechanisms needs to be made when evaluating cancer
      patients, and treatment aimed at secondary prevention needs to incorporate
      overall prognosis and goals of care.

PMID- 16635427
TI  - Paraneoplastic neurologic syndromes.
AB  - Paraneoplastic neurologic disorders (PND) are remote medical complications of
      cancer that cannot be attributed to direct effects of the neoplasm or its
      metastases. PND are uncommon, disabling syndromes that have been recognized for
      more than 50 years. Despite their rarity, these diseases are the subject of
      intensive research and clinical fascination. This review highlights notable
      recent publications related to PND. In recent years, the broad clinical spectrum
      of PND has become even more apparent. PND can affect any part of the central or
      peripheral nervous system and often affect multiple areas simultaneously. These
      disorders are often associated with neuron-specific autoantibodies in the serum
      and cerebrospinal fluid. In clinical practice, detection of these antibodies is
      crucial for the diagnosis because the neurologic symptoms usually precede the
      diagnosis of cancer. Recent publications have described new antibody
      specificities associated with PND and expand our ability to identify patients
      serologically. Once diagnosed, detection of cancer can be difficult, but the use
      of positron emission tomography has been shown to be a useful supplement to
      standard imaging procedures. PND are thought to be autoimmune disorders
      precipitated by the immune response to cancer. Observations and laboratory
      studies in PND patients have shown that activation of cytotoxic T cells is an
      important component of the disease. These studies not only shed light on the
      pathogenesis of PND and the mechanisms of effective antitumor immunity but may
      eventually lead to improved treatment.

PMID- 16635429
TI  - Image-guided intensity-modulated radiation therapy of spine tumors.
AB  - Recent advancements in imaging technology have made it possible to deliver very
      precise radiotherapy. By imaging the patient at the time of actual treatment,
      immediate corrections in patient positioning and set-up errors have become
      possible. Reduction in these types of treatment errors has had a significant
      impact upon the radiotherapeutic management of spine tumors because doses of
      radiation that exceed spinal cord tolerance can now be given within very close
      proximity to the cord. Also, the normal tissue margin around the target volume
      can be reduced, resulting in less of the dose being delivered to nearby critical
      organs. These factors have combined to improve patient outcomes, both in terms of
      tumor control and lower toxicity. The recent medical literature has reflected a
      growing interest in the application of image-guided technology to the treatment
      of paraspinal tumors. This review summarizes the significant contributions to the
      medical literature over the past calendar year.

PMID- 16635428
TI  - Medulloblastoma: therapy and biologic considerations.
AB  - Tremendous strides have been made in both the treatment and the biologic
      understanding of medulloblastoma. Present optimal treatment can cure most
      medulloblastoma patients. A substantial minority of patients, however, will have
      recurrent or progressive disease. Recent studies have demonstrated that the
      success of treatment is not simply a matter of chance, but rather can be
      predicted based on specific biologic markers. These markers predict outcome
      independent of clinical staging and make clear that medulloblastomas are a
      biologically diverse group of tumors with variable clinical behavior. Molecular
      biologic investigation, including replication of tumorigenesis in transgenic
      mice, has further elucidated the complex biology of medulloblastoma. Current
      standard and investigational treatments, however, do not yet make use of biologic
      markers that predict risk of recurrence. Practical limitations have slowed the
      pace at which treatment paradigms can be revised to incorporate biologic
      insights. Mouse medulloblastoma models may provide an important bridge between
      biologic investigation and the development of new therapeutic approaches.

PMID- 16635430
TI  - Recent advances in the treatment of oligodendrogliomas.
AB  - The optimal treatment for patients with oligodendrogliomas is unknown, and
      current management strategies remain controversial. This past year, further
      exploration of the molecular genetics of the tumors and its prognostic
      implications for outcome, evaluation of the utility of positron emission
      tomography imaging, and the role of radiation and chemotherapy in the treatment
      of oligodendrogliomas have been reported. It is becoming increasingly apparent
      that oligodendrogliomas are several distinct diseases on a molecular level, and
      that key genetic derangements can signify a response to treatment and favorable
      outcome. The added contributions of recent publications consolidates these
      emerging impressions. Ultimately, the combination of improved imaging techniques,
      molecular profiling, and new therapies should result in improved outcome with
      reduced treatment-related toxicity for patients with newly diagnosed,
      progressive, and recurrent oligodendrogliomas.

PMID- 16635431
TI  - Neurologic toxicities of cancer therapies.
AB  - Neurologic dysfunction is a well-recognized adverse effect of cancer
      therapeutics. The most common manifestations include peripheral neuropathy and
      encephalopathy. Often, symptoms resolve or improve upon removal of the offending
      agent; therefore, it is essential that clinicians recognize the symptoms and
      signs of injury. Occasionally, symptoms persist or develop after discontinuation
      of medication and may culminate in disability and diminished quality of life. As
      our understanding of neurotoxicity improves, medications with less potential for
      injury may be developed. In addition, potential antidotes to prevent or reverse
      injury may emerge. This review focuses on the clinical features, mechanisms, and
      possible therapeutics of the neurotoxicity of chemotherapy. In particular,
      oxaliplatin, thalidomide, methotrexate, ifosfamide, cytarabine, amifostine,
      acetyl-L-carnitine, methylene blue, cytokines, and neurotrophins are discussed.

PMID- 16635432
TI  - Remyelination strategies: new advancements toward a regenerative treatment in
      multiple sclerosis.
AB  - Spontaneous remyelination and repair mechanisms in multiple sclerosis are mostly
      insufficient and contribute to clinical disability. Treatments improving these
      processes are not yet available but basic research in animal models has led to
      the proposal of several repair strategies. These include enhancement of the
      naturally occurring mechanisms, remyelination due to a change of the immune
      response, and transfer of myelinating cells. Despite the encouraging experimental
      findings and the constantly increasing knowledge of the molecular mechanisms of
      remyelination and remyelination failure, there remain many questions before this
      knowledge can be successfully translated into clinical trials.

PMID- 16635433
TI  - Demyelinating disorders: update on transverse myelitis.
AB  - Transverse myelitis (TM) is a focal inflammatory disorder of the spinal cord.
      Perivascular monocytic and lymphocytic infiltration, demyelination, and axonal
      injury are prominent histopathogic features of TM. The clinical manifestations of
      TM are consequent to dysfunction of motor, sensory, and autonomic pathways. At
      peak deficit, 50% of patients with TM are completely paraplegic (with no
      volitional movements of legs), virtually all have some degree of bladder
      dysfunction, and 80% to 94% have numbness, paresthesias, or band-like
      dysesthesias. Longitudinal case series of TM reveal that approximately one third
      of patients recover with little to no sequelae, one third are left with a
      moderate degree of permanent disability, and one third have severe disability.
      Recent studies have shown that the cytokine interleukin-6 may be a useful
      biomarker, as the levels of interleukin-6 in the cerebrospinal fluid of acute TM
      patients strongly correlate with and are highly predictive of disability.
      Clinical trials testing the efficacy of promising axonoprotective agents in
      combination with intravenous steroids in the treatment of TM are currently
      underway.

PMID- 16635434
TI  - Role of mitochondria in multiple sclerosis.
AB  - This review presents inherited and acquired forms of mitochondrial dysfunction
      associated with oligodendrocytopathy and neurodegeneration in order to better
      understand the degenerative features of inflammatory demyelination. The
      recognition that various mitochondrial mechanisms are involved in the
      pathogenesis of multiple sclerosis leads to therapeutic considerations, re
      emphasizing the importance of early neuroprotection in combination with the
      approved means of immune modulation.

PMID- 16635435
TI  - Progressive multifocal leukoencephalopathy and multiple sclerosis: lessons from
      natalizumab.
AB  - Three patients have developed progressive multifocal leukoencephalopathy while
      being treated with natalizumab for their autoimmune diseases. One patient had
      relapsing-remitting multiple sclerosis (RRMS), one had Crohn's disease, and one
      (who had been enrolled in an RRMS phase III trial) had no evidence of multiple
      sclerosis on autopsy. The patient with RRMS now has severe, permanent neurologic
      damage and the other two patients died. In this article, we recommend revised
      entry and diagnostic criteria to prevent enrollment of RRMS patients with a
      favorable prognosis or questionable diagnosis into trials of drugs with unknown
      safety profiles. In light of the risk of progressive multifocal
      leukoencephalopathy, we strongly recommend that RRMS patients who are at low risk
      of disability not be treated with natalizumab. Finally, we discuss what
      additional natalizumab efficacy data need to be presented before any decisions
      should be made about treating RRMS patients with a high risk of developing long
      term disability.

PMID- 16635436
TI  - Complementary and alternative medicine: is there a role in multiple sclerosis?
AB  - Despite effective conventional therapies for multiple sclerosis (MS), many people
      with MS explore complementary and alternative medicine (CAM) therapies for their
      symptoms. Common CAM therapies that people use include dietary modification,
      nutritional and herbal supplementation, and mind-body therapies. There is a
      revival of interest among MS researchers about the therapeutic potential of low
      fat diet and essential fatty acid supplementation in MS. The efficacy of specific
      vitamin supplementation remains unclear. Recently, cannabis and yoga have been
      studied in more controlled studies and have provided evidence that they may have
      some benefit. The research on CAM therapies in MS is still exploratory, but
      considering peoples' interest and common use of these therapies, further research
      in this area is clearly warranted.

PMID- 16635437
TI  - Role of FLAP and PDE4D in myocardial infarction and stroke: target discovery and
      future treatment options.
AB  - Biomarkers such as C-reactive protein (CRP) and myeloperoxidase (MPO) are
      elevated in patients with coronary artery disease and confer risk of acute
      cardiovascular events, such as myocardial infarction (MI) and stroke. More
      recently, variants in the 5-lipoxygenase-activating protein (FLAP) gene were
      shown to confer risk to both MI and stroke, effects that appear to be mediated
      through elevated LTB(4), a chemoattractant mediator shown to be upregulated in
      patients with MI. Another gene in the leukotriene (LT) pathway, LTA(4) hydrolase,
      was subsequently found to confer increased risk to MI, effects that were
      ethnicity-specific with an approximately threefold higher risk in African
      Americans than in whites. In another study, markers in the phosphodiesterase
      (PDE) 4D gene were found to confer risk to large-vessel occlusive and cardiogenic
      stroke. Interestingly, there is a cross-link between the 5-LO and the PDE4D
      pathways with converging biology. To address the role of an inhibitor of FLAP on
      biomarkers of MI risk, a randomized placebo-controlled phase II trial was
      conducted in patients with MI. This trial showed that LTB(4) and MPO production
      was reduced in whole blood leukocytes that were stimulated with ionomycin and the
      effects of the inhibitor were dose dependent. Serum CRP and plasma MPO were also
      reduced at the highest dose, which was well tolerated. These data suggest that
      LTB(4) is a risk factor of MI and that inhibition of FLAP and the LT pathway
      produces suppression of biomarkers that are associated with MI risk, including
      but not limited to LTB(4), MPO, and CRP, supporting the notion that the LTB(4)
      arm of the LT pathway may play a fundamental role in heart attacks and stroke.

PMID- 16635438
TI  - Transient ischemic attack: are there different types or classes? Risk of stroke
      and treatment options.
AB  - Recent advances in neuroimaging have revolutionized the evaluation of the
      clinical syndrome of transient ischemic attack (TIA). Diffusion-weighted imaging
      demonstrates microinfarctions (< 1 cm(3)) in approximately 50% of patients with
      TIA, establishing that not all clinically transient spells are transient at the
      tissue level. The clinical syndrome of TIA that is associated with ischemic brain
      injury is called "transient symptoms with infarction" (TSI). TSI appears to be a
      different subset because it harbors higher risk of imminent stroke than "TIA with
      no infarction." Armed with the evidence of ischemia as the cause of transient
      spell, clinicians can pursue the most appropriate therapy for stroke prevention
      by targeting the underlying etiology of brain ischemia.

PMID- 16635439
TI  - Benign cerebral angiopathy; postpartum cerebral angiopathy: characteristics and
      treatment.
AB  - Benign cerebral angiopathy and postpartum cerebral angiopathy are reversible
      cerebral arterial vasoconstriction syndromes. Presentation includes recurrent
      severe headaches, altered consciousness, and focal neurologic deficits; ischemic
      and/or hemorrhagic strokes can occur. No standard management has been
      established, but most authors agree that 1) acute-phase treatment includes
      cessation of vasoconstrictors, treatment of associated conditions, vasospasm
      treatment (calcium channel antagonists), and corticosteroids; 2) other measures
      include headache relief, blood pressure control, and stroke, cerebral edema, and
      seizure treatment; 3) definitive diagnosis requires conventional angiography and
      exclusion of alternative diagnosis; 4) a second arterial examination after 4 to 6
      weeks is mandatory to confirm reversibility of vasoconstriction; 5) brain biopsy
      is indicated to rule out cerebral vasculitis in severe cases with clinical
      deterioration under steroid treatment or atypical findings; 6) immunosuppression
      should be reserved for patients with brain-leptomeningeal biopsy-proven
      vasculitis or used while waiting for a brain biopsy result; and 7) long-term
      measures include secondary stroke prevention and treatment of complications.

PMID- 16635440
TI  - Endothelial function and cerebrovascular disease: implications for diagnosis and
      treatment.
AB  - Cerebrovascular disease remains one of the most common causes of morbidity and
      mortality in the United States. There is strong evidence to implicate endothelial
      dysfunction in the initiation and progression of atherosclerosis and its
      complications. It is now well known that endothelial dysfunction represents a
      systemic syndrome involving multiple vascular beds, including the cerebral
      vasculature. Currently, no gold standard treatment for endothelial dysfunction
      exists. Nonetheless, several treatment strategies have been found to be helpful
      in improving endothelial function. A few of these strategies have been implicated
      in stroke risk reduction as well, adding another line of evidence to the
      relationship between endothelial function and cerebrovascular disease.

PMID- 16635441
TI  - The action of dipyridamole to prevent thrombosis: practical implications for the
      treatment and prevention of stroke.
AB  - Aggrenox (Boehringer Ingelheim, Ingelheim, Germany), a novel combination of low
      dose aspirin with dipyridamole, represents a safe and promising combination
      alternative for mild but sustained platelet inhibition, and reduction of both
      arterial and venous thrombi occurrences. In a large, well-controlled randomized
      trial (ESPS-2 ) evaluating antiplatelet agents for stroke prevention, Aggrenox
      was twice as effective as monotherapy with either aspirin or dipyridamole. There
      is an increasing body of evidence that a delicate strategy with Aggrenox provides
      modest inhibition of platelet activity, especially in a chronic, long-term
      setting. Mild platelet inhibition beyond conventional aggregation may represent a
      substantial advantage over aggressive antiplatelet regimens for the treatment,
      and especially for secondary prevention, of cerebrovascular ischemic events.
      Although there is no doubt that the concept of inhibiting platelets is vital for
      the treatment of vascular ischemic disease in general and ischemic stroke and
      transient ischemic attack (TIA) in particular, the optimal degree of such
      inhibition still remains an unsolved mystery. It seems that the concepts of "the
      more, the better" and "one size fits all" may no longer be valid for ideal
      antiplatelet protection in such high-risk populations. Without routine individual
      laboratory assessment of platelet function, mild regimens have the advantage of
      being more suitable for the majority of patients and will contribute
      substantially to the success of dipyridamole. Conversely, if we can determine
      baseline platelet status and intelligently apply therapy based on platelet
      activity in each particular patient, clinical outcomes may be better. Avoiding
      excessive bleeding risks after aggressive strategies in patients with normal or
      already decreased platelet function, but targeting those who exhibit activated
      platelets, may improve risk stratification and save lives. Therefore, Aggrenox
      should be considered a drug of choice to prevent the second stroke. Eliminating,
      or at least minimizing, the most frequent side effect, namely transitory
      headaches at the beginning of therapy with Aggrenox, will benefit patients and
      increase the use of this agent. Should the PRoFESS (Prevention Regimen For
      Effectively avoiding Second Strokes) trial show an advantage in event reduction
      with Aggrenox over clopidogrel, the increase will be especially dramatic. In
      short, based on current evidence most guidelines include Aggrenox as a first-line
      option for secondary prevention of ischemic stroke or TIA, and some recent
      versions suggest it may be preferable in other clinical scenarios.

PMID- 16635442
TI  - Reversible cerebral vasoconstriction syndromes.
AB  - Reversible cerebral vasoconstriction syndromes (RCVS) comprise a set of
      conditions having in common the apoplectic onset of headache mimicking
      subarachnoid hemorrhage, focal or multifocal neurologic deficits with a
      predilection for visual processing disorders, multifocal vasoconstriction on
      cerebral angiography, noninflammatory spinal fluid, and a generally benign
      prognosis. RCVS may occur in the setting of the puerperium, after intracranial
      surgery, in association with prescription or illicit drug use, in migraineurs, or
      without a clear trigger. Distinction from central nervous system vasculitis is
      important and is often possible using routine clinical assessment, without brain
      biopsy. No treatments are of proven value in RCVS. Empiric treatments include the
      use of calcium channel blockers, steroids, induced hypertension or blood pressure
      lowering, and rarely endovascular therapy. The key to successful management is
      accurate diagnosis and cognizance of the tendency of RCVS to resolve without long
      term immunosuppressive treatment.

PMID- 16635443
TI  - The use of neurovascular imaging for triaging TIA and minor stroke: implications
      for therapy.
AB  - Nondisabling cerebrovascular events (minor stroke or transient ischemic attack)
      are not benign; a significant proportion of these patients will suffer a new
      disabling stroke or develop stroke progression in hospital, resulting in
      dependence or death. With the exception of the modest benefits of aspirin, there
      are currently no effective acute medical therapies to prevent early progression
      or recurrence in such patients. Early carotid revascularization appears to be the
      most efficacious treatment available for patients with symptomatic (> 50%)
      internal carotid artery stenosis. More acute treatment and acute prevention
      trials are needed. MRI, CT bolus techniques, and transcranial Doppler emboli
      detection represent tools for detection of patients at high risk for
      deterioration and should be incorporated into the development of effective
      therapies by targeting the most appropriate patients for intervention.

PMID- 16635444
TI  - Vascular cognitive impairment.
AB  - Vascular cognitive impairment encompasses a spectrum of clinically defined
      syndromes ranging from vascular cognitive impairment-no dementia, to vascular
      dementia. The underlying cerebrovascular pathology includes both overt infarction
      as well as rarefaction of gray and white matter. Alzheimer's pathology may
      coexist with vascular pathology. Diagnosis rests on identifying acquired
      cognitive impairment in the setting of documented cerebrovascular disease, based
      on clinical presentation and neuroimaging; MRI is more sensitive than CT. The
      course can be stepwise or gradually progressive. The clinical picture is
      typically dominated by deficits in executive function rather than the short-term
      memory deficit typical of Alzheimer's disease. No specific therapies exist, but
      treatment with anticholinesterase agents and N-methyl-d-aspartate antagonists may
      result in clinical improvement. Prevention remains paramount, with early
      recognition of populations at risk and early and aggressive management of risk
      factors, including hypertension, dyslipidemia, diabetes, and tobacco use as well
      as antithrombotic therapy, in appropriate populations.

PMID- 16635445
TI  - Platelet microparticles and platelet adhesion: therapeutic implications for the
      prevention and treatment of stroke.
AB  - Platelets are believed to play a part in all stages of the pathogenesis of
      ischemic stroke, from the initial formation of the atherosclerotic plaque,
      through plaque destabilization to the development of neuronal cell death. A
      process common to all of these pathogenic changes is the ability of the activated
      platelet to adhere to the site of disease. In addition, the release of the
      membrane vesicles from platelets enhances many of these processes. Therefore, an
      understanding of platelet adhesion and platelet microparticle release can aid the
      development toward the treatment and prevention of stroke. There has been much
      research into interventions that can reduce platelet activation in
      atherosclerosis and stroke. The benefits of nonpharmacologic interventions in
      stroke, such as diet and lifestyle modification, may in part be mediated by their
      effects on platelet activation. In addition, the antiplatelet drug aspirin has
      been shown to be useful in both the treatment of acute stroke and the secondary
      prevention of atherothrombosis. Other antiplatelet agents, such as the
      glycoprotein IIb/IIIa inhibitors and triflusal, are currently being evaluated for
      the treatment of acute atherothrombotic stroke.

PMID- 16635446
TI  - Thrombophilia in ischemic stroke subtypes: implications for treatment.
AB  - The current understanding of thrombogenesis is modeled on Virchow's triad:
      stasis, hypercoagulability, and vessel wall injury. There is a dynamic (always
      changing) nonlinear interaction between the vascular wall, blood components, and
      flow, which at times defined "pathologic" leads to thrombosis or hemorrhage, at
      other times called "healthy" to normal hemostasis. The triad named after Virchow
      was not designated as such in Virchow's work. Instead, Virchow showed that
      thrombosis itself leads to endothelial damage, hypercoagulability, and stasis.
      Thus, cause and effect regarding the elements of Virchow's triad and thrombosis
      become indistinguishable if linearity is considered mandatory. Considering a
      nonlinear relation solves this problem. In the real patient, each element is
      present to a degree. At every moment in time, the direction of coagulation
      (toward hemostasis, thrombosis, or hemorrhage) and the dynamic of interaction of
      the elements of the triad change. The complexity and nonlinearity of the
      thrombotic context is evident. These facts suggest a new venue for diagnostic
      classification of stroke (ischemic and hemorrhagic) by causation and have
      implications for its prevention and treatment. Clinical and laboratory evidence
      can be gathered for the elements of Virchow's triad as well as for fibrinolysis
      and thrombosis. Mathematical methods other than probability-based statistics can
      represent the measured presence of these elements to a degree and their nonlinear
      relationship. These include, but may not be limited to, Riemannian geometry,
      fuzzy logic, cellular automata, and infinitesimals, all proscribed by evidence
      based medicine. However, by using these methods, diagnosis and treatment measures
      for stroke can be built on a causal rather than risk methodology, individualizing
      medical decisions to the patient. All current clinical guidelines are based on
      linear methods of probability-based statistics and group-based data. The
      therapeutic choice of antithrombotic therapy in the individual patient for whom
      measured elements of thrombogenesis are available rests on the knowledge and
      expertise of the treating physician.

PMID- 16635447
TI  - Prediction of IBD based on population history for fine gene mapping.
AB  - A novel multiple regression method (RM) is developed to predict identity-by
      descent probabilities at a locus L (IBDL), among individuals without pedigree,
      given information on surrounding markers and population history. These IBDL
      probabilities are a function of the increase in linkage disequilibrium (LD)
      generated by drift in a homogeneous population over generations. Three parameters
      are sufficient to describe population history: effective population size (Ne),
      number of generations since foundation (T), and marker allele frequencies among
      founders (p). IBDL are used in a simulation study to map a quantitative trait
      locus (QTL) via variance component estimation. RM is compared to a coalescent
      method (CM) in terms of power and robustness of QTL detection. Differences
      between RM and CM are small but significant. For example, RM is more powerful
      than CM in dioecious populations, but not in monoecious populations. Moreover, RM
      is more robust than CM when marker phases are unknown or when there is complete
      LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises
      all marker haplotype information, whereas RM utilises information contained in
      each individual marker and all possible marker pairs but not in higher order
      interactions. RM consists of a family of models encompassing four different
      population structures, and two ways of using marker information, which contrasts
      with the single model that must cater for all possible evolutionary scenarios in
      CM.

PMID- 16635448
TI  - Efficient computation of the inverse of gametic relationship matrix for a marked
      QTL.
AB  - Best linear unbiased prediction of genetic merits for a marked quantitative trait
      locus (QTL) using mixed model methodology includes the inverse of conditional
      gametic relationship matrix (G-1) for a marked QTL. When accounting for
      inbreeding, the conditional gametic relationships between two parents of
      individuals for a marked QTL are necessary to build G-1 directly. Up to now, the
      tabular method and its adaptations have been used to compute these relationships.
      In the present paper, an indirect method was implemented at the gametic level to
      compute these few relationships. Simulation results showed that the indirect
      method can perform faster with significantly less storage requirements than
      adaptation of the tabular method. The efficiency of the indirect method was
      mainly due to the use of the sparseness of G-1. The indirect method can also be
      applied to construct an approximate G-1 for populations with incomplete marker
      data, providing approximate probabilities of descent for QTL alleles for
      individuals with incomplete marker data.

PMID- 16635449
TI  - Parallel computations on pedigree data through mapping to configurable computing
      devices.
AB  - Pedigree data structures have a number of applications in genetics, including the
      estimation of allelic or haplotype probabilities in humans and agricultural
      species, and the estimation of breeding values in agricultural species.
      Sequential algorithms for general purpose CPU-based computers are commonly used,
      but are inadequate for some tasks on large data sets. We show that pedigree data
      can be directly represented on Field Programmable Gate Arrays (FPGA), allowing
      highly efficient massively parallel simulation of the flow of genes. Operating on
      the whole pedigree in parallel, the transmission of genes can occur for all
      individuals in a single clock cycle. By using FPGA, the algorithms to estimate
      inbreeding coefficients and allelic probabilities are shown to operate hundreds
      to thousands of times faster than the corresponding sequentially based
      algorithms. Where problems can be largely represented in an integer form, FPGA
      provide an efficient platform for computations on pedigree data.

PMID- 16635450
TI  - Analysis of rabbit doe longevity using a semiparametric log-Normal animal frailty
      model with time-dependent covariates.
AB  - Data on doe longevity in a rabbit population were analysed using a semiparametric
      log-Normal animal frailty model. Longevity was defined as the time from the first
      positive pregnancy test to death or culling due to pathological problems. Does
      culled for other reasons had right censored records of longevity. The model
      included time dependent covariates associated with year by season, the
      interaction between physiological state and the number of young born alive, and
      between order of positive pregnancy test and physiological state. The model also
      included an additive genetic effect and a residual in log frailty. Properties of
      marginal posterior distributions of specific parameters were inferred from a full
      Bayesian analysis using Gibbs sampling. All of the fully conditional posterior
      distributions defining a Gibbs sampler were easy to sample from, either directly
      or using adaptive rejection sampling. The marginal posterior mean estimates of
      the additive genetic variance and of the residual variance in log frailty were
      0.247 and 0.690.

PMID- 16635451
TI  - Fatness QTL on chicken chromosome 5 and interaction with sex.
AB  - Quantitative trait loci (QTL) affecting fatness in male chickens were previously
      identified on chromosome 5 (GGA5) in a three-generation design derived from two
      experimental chicken lines divergently selected for abdominal fat weight. A new
      design, established from the same pure lines, produced 407 F2 progenies (males
      and females) from 4 F1-sire families. Body weight and abdominal fat were measured
      on the F2 at 9 wk of age. In each sire family, selective genotyping was carried
      out for 48 extreme individuals for abdominal fat using seven microsatellite
      markers from GGA5. QTL analyses confirmed the presence of QTL for fatness on GGA5
      and identified a QTL by sex interaction. By crossing one F1 sire heterozygous at
      the QTL with lean line dams, three recombinant backcross 1 (BC1) males were
      produced and their QTL genotypes were assessed in backcross 2 (BC2) progenies.
      These results confirmed the QTL by sex interaction identified in the F2
      generation and they allow mapping of the female QTL to less than 8 Mb at the
      distal part of the GGA5. They also indicate that fat QTL alleles were segregating
      in both fat and lean lines.

PMID- 16635452
TI  - A 7-bp insertion in the 3' untranslated region suggests the duplication and
      concerted evolution of the rabbit SRY gene.
AB  - In this work we report the genetic polymorphism of a 7-bp insertion in the 3'
      untranslated region of the rabbit SRY gene. The polymorphic GAATTAA motif was
      found exclusively in one of the two divergent rabbit Y-chromosomal lineages,
      suggesting that its origin is more recent than the separation of the O. c.
      algirus and O. c. cuniculus Y-chromosomes. In addition, the remarkable
      observation of haplotypes exhibiting 0, 1 and 2 7-bp inserts in essentially all
      algirus populations suggests that the rabbit SRY gene is duplicated and evolving
      under concerted evolution.

PMID- 16635453
TI  - Testing the neutral theory of molecular evolution using genomic data: a
      comparison of the human and bovine transcriptome.
AB  - Despite growing evidence of rapid evolution in protein coding genes, the
      contribution of positive selection to intra- and interspecific differences in
      protein coding regions of the genome is unclear. We attempted to see if genes
      coding for secreted proteins and genes with narrow expression, specifically those
      preferentially expressed in the mammary gland, have diverged at a faster rate
      between domestic cattle (Bos taurus) and humans (Homo sapiens) than other genes
      and whether positive selection is responsible. Using a large data set, we
      identified groups of genes based on secretion and expression patterns and
      compared them for the rate of nonsynonymous (dN) and synonymous (dS)
      substitutions per site and the number of radical (Dr) and conservative (Dc) amino
      acid substitutions. We found evidence of rapid evolution in genes with narrow
      expression, especially for those expressed in the liver and mammary gland and for
      genes coding for secreted proteins. We compared common human polymorphism data
      with human-cattle divergence and found that genes with high evolutionary rates in
      human-cattle divergence also had a large number of common human polymorphisms.
      This argues against positive selection causing rapid divergence in these groups
      of genes. In most cases dN/dS ratios were lower in human-cattle divergence than
      in common human polymorphism presumably due to differences in the effectiveness
      of purifying selection between long-term divergence and short-term polymorphism.

PMID- 16635454
TI  - Distribution and immunohistochemical characterization of primary afferent neurons
      innervating the levator ani muscle of the female squirrel monkey.
AB  - OBJECTIVE: This study was undertaken to examine the neurofilament and
      neurochemical composition of subpopulations of primary afferent neurons
      innervating the levator ani muscle by combining retrograde tracing and triple
      labeling immunofluorescence in the female squirrel monkey. STUDY DESIGN: Cholera
      toxin B subunit (CTB) was injected unilaterally into the levator ani muscle of 3
      monkeys to identify primary sensory neurons in the dorsal root ganglia (DRG) and
      their central projections in the spinal cord. L7-S2 DRG were processed for dual
      or triple labeling immunofluorescence 3 days after injection to examine labeling
      of the 200 kD neurofilament marker RT97 (a marker of myelinated neurons),
      calcitonin gene-related peptide (CGRP; a marker of peptidergic neurons),
      isolectin B4 (IB4; a marker of small, unmyelinated neurons), and nerve growth
      factor receptor (TrkA) in CTB-positive neurons. RESULTS: RT97-negative (C-fiber)
      neurons were more numerous (74% of total CTB-labeled neurons) and smaller in size
      than RT97-positive (A-fiber) afferent neurons (26% of CTB-labeled neurons). IB4
      labeling was almost exclusively found in RT97-negative afferent neurons.
      Approximately 43% of all CTB-labeled DRG neurons expressed CGRP, and the majority
      of these were small. The distribution and sizes of CTB-labeled TrkA-positive DRG
      neurons were similar to those of CTB-labeled CGRP-positive DRG neurons.
      CONCLUSION: The levator ani muscle is innervated by 3 major subpopulations of
      primary afferent neurons consisting of cells with large, neurofilament-rich soma
      and A fibers (putative proprioceptive neurons) and those with small, peptidergic
      or nonpeptidergic, neurofilament-poor soma and C fibers (putative nociceptive,
      mechanoreceptive, ergoreceptive, and thermoreceptive neurons). Future
      investigation is needed to elucidate the relationship between primary sensory
      neuron subpopulations and changes in neuropeptide and neurotrophin expression on
      experimental levator ani nerve damage, childbirth, and aging.

PMID- 16635455
TI  - PAPP-A and osteoprotegerin, together with interleukin-8 and RANTES, are elevated
      in the peritoneal fluid of women with endometriosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether pregnancy-associated
      plasma protein A, glycodelin, osteoprotegerin, and soluble CD163 are possible
      peritoneal fluid markers for endometriosis and to compare them with the
      established chemokine markers interleukin-8 and regulated on activation, normal T
      cell expressed and secreted. STUDY DESIGN: Determination of the concentrations of
      interleukin-8, regulated on activation, normal T-cell expressed and secreted,
      pregnancy-associated plasma protein A, glycodelin, CD163, osteoprotegerin, and
      progesterone in the peritoneal fluid collected from women undergoing laparoscopy.
      RESULTS: From a total of 132 women, 77 women were diagnosed with endometriosis,
      and 55 women were free of the disease and served as control subjects. Pregnancy
      associated plasma protein A and osteoprotegerin showed significantly (P < 0.05)
      elevated peritoneal fluid concentrations as a function of the severity of the
      disease, together with interleukin-8 and regulated on activation, normal T-cell
      expressed and secreted (P < .001). Glycodelin and CD163 did not differ between
      cases and control subjects. Many of these marker concentrations were
      intercorrelated strongly. CONCLUSION: Pregnancy-associated plasma protein A and
      osteoprotegerin may play a role in the inflammation process of endometriosis, but
      interleukin-8 and regulated on activation, normal T-cell expressed and secreted
      are superior peritoneal fluid markers.

PMID- 16635456
TI  - Maternal oxygen administration and fetal cerebral oxygenation: studies on near
      term fetal lambs at both low and high altitude.
AB  - OBJECTIVE: We tested the hypothesis that O2 administration to the mother would
      increase arterial O2 tension (PaO2) and cortical tissue O2 tension (tPO2) in both
      the normoxic control fetus and that acclimatized to high altitude, and that this
      effect might be greater in the high altitude fetus than that at sea level. STUDY
      DESIGN: Pregnant ewes were divided into either low-altitude group or high
      altitude group (3820 m; maintained from day 30 of gestation to near-term, term =
      145 days; n = 6 each). In near-term fetuses we instrumented the cerebral cortex
      with tissue PO2-laser Doppler flow probes, and placed arterial catheters. With
      the ewe breathing either air or 50% O2, we measured fetal arterial and brain
      tissue PO2 and cerebral blood flow (CBF). RESULTS: In response to maternal O2
      administration, in both low- and high-altitude fetuses, PaO2, O2 content, and
      brain tissue PO2 increased significantly. Nonetheless, the fetuses at high
      altitude showed significantly greater increase in both PaO2 and cerebral tPO2,
      than that seen in fetuses at low altitude. In neither group was there a change in
      CBF or cerebral metabolic rate for O2. CONCLUSION: Maternal O2 administration
      significantly increased PaO2 and cerebral tPO2 of the fetus both at low altitude
      and at high altitude, with this increase being greater in the high altitude
      animals. We suggest that maternal O2 administration can have an important effect
      in ameliorating nonreassuring fetal status, and perhaps be of value in instances
      of mothers who smoke heavily or with cardiopulmonary disease.

PMID- 16635457
TI  - The influence of physician gender on practice satisfaction among obstetrician
      gynecologists.
AB  - OBJECTIVE: A survey was conducted to investigate the hypothesis that female
      gender would positively affect job satisfaction among obstetrician gynecologists.
      STUDY DESIGN: A survey was sent to 500 randomized, age matched American College
      of Obstetrics and Gynecology members, 50% each men and women: 49.8% responded.
      Data were analyzed with the chi2 contingency test, Cochran's test for linear
      trends, Student t tests, and multiple regression. RESULTS: Women considered their
      gender an asset in deciding on a career in obstetrics and gynecology, in
      obtaining jobs, and in maintaining their practices. Men considered that their
      gender limited their practice options and were more likely to report that they
      would not choose a career in obstetrics and gynecology if they could choose
      again. The only significant difference between men and women in measures of
      obtaining and maintaining a practice was that men were more likely to practice in
      small urban or rural settings. Men reported higher incomes. Both genders were
      equally satisfied with their jobs. CONCLUSION: Although both genders considered
      female gender to be an asset in obstetrics and gynecology, this survey showed no
      difference in their ratings of overall career satisfaction.

PMID- 16635458
TI  - Antepartum seafood consumption and mercury levels in newborn cord blood.
AB  - OBJECTIVE: The purpose of this study was to determine the level of fetal mercury
      exposure by measuring mercury levels in newborn cord blood and to analyze the
      association with fish consumption during pregnancy. STUDY DESIGN: A total of 308
      women who met the eligibility criteria were enrolled in the study. Of these, 275
      women completed a dietary survey; after delivery, cord blood was collected and
      analyzed for mercury levels. RESULTS: The mean mercury level in cord blood was
      4.82 microg/L; 28.3% of the participants had measured mercury levels above the US
      Environmental Protection Agency's recommended reference dose (5.8 microg/L). A
      significant relationship was noted between the amount of fish consumed during
      pregnancy and rising mercury levels in cord blood. CONCLUSION: In an island state
      with high levels of fish consumption, women were 3 times more likely to have
      elevated cord blood mercury levels, compared with the national average.

PMID- 16635460
TI  - Dexamethasone treatment and HELLP syndrome.

PMID- 16635463
TI  - A comprehensive women's health care center: are gynecologists offering primary
      care?
AB  - OBJECTIVE: The purpose of this study was to compare patient characteristics and
      diagnoses in a comprehensive Women's Health Care Clinic between gynecologists and
      internal medicine physicians. STUDY DESIGN: This retrospective cohort study
      evaluated International Classification of Diseases, 9th Revision, codes that were
      recorded between January 1, 2001, and January 4, 2004, at the Women's Health Care
      Clinic. We compared demographics and prevalence of diagnosis codes for patients
      who were seen by obstetricians/gynecologists and internal medicine physicians and
      compared these data with national survey statistics. A sampling of charts was
      reviewed for coding verification. RESULTS: We analyzed 13,462 visits at the
      Women's Health Care Clinic. Patients who were seen by internists were older, had
      greater racial diversity, and had more gender-nonspecific medical disorders
      (hypertension, depression). Gynecologists saw more specific women's health
      problems (P < .05). The diagnoses of menstrual disorders, menopause, pelvic pain,
      and abnormal cytologic findings within the Women's Health Care Clinic follow
      closely with the national ambulatory survey data. CONCLUSION: Within this
      multispecialty Women's Health Care Clinic, internal medicine physicians are
      practicing primary care and obstetricians/gynecologists are providing specialty
      care.

PMID- 16635464
TI  - Sexual assault victims: factors associated with follow-up care.
AB  - OBJECTIVE: This study was undertaken to describe patient, assault, and
      examination characteristics associated with compliance with follow-up in sexual
      assault victims. STUDY DESIGN: We conducted a retrospective cohort study of
      consecutive women presenting to an urban hospital after sexual assault over a 36
      month period. We compared those who did and did not follow-up by using
      standardized history, examination, and data collection forms. RESULTS: Eight
      hundred twelve women met inclusion criteria; 288 (35.5%) attended follow-up.
      Young age (odds ratio [OR] = 2.70), assault at home (OR = 1.90), amnesia (OR =
      1.80), alcohol use (OR = 1.55), genital trauma (OR = 1.55), and receipt of
      postexamination medications (OR = 1.87) were associated with greater follow-up;
      homelessness (OR = 0.30), psychiatric diagnosis (OR = 0.34), assault by an
      intimate partner (OR = 0.47), and cocaine use (OR = 0.29) with less. CONCLUSION:
      Although only 35.5% of sexual assault victims seek follow-up, we found many
      factors positively and negatively associated with this. These findings may inform
      care strategies designed to improve follow-up for women who are at risk for
      significant sequelae.

PMID- 16635466
TI  - A new hypothesis about the origin of uterine fibroids based on gene expression
      profiling with microarrays.
AB  - This article will discuss some recent insights based on our microarray studies
      that have emphasized the role the extracellular matrix, transforming growth
      factor beta, and collagen structure in fibroid formation. These studies led to
      appreciation of molecular similarities between fibroids and keloids.
      Collectively, these observations suggest a model of fibroid development based on
      an abnormal response to tissue repair, resulting in disordered healing and
      formation of an altered extracellular matrix.

PMID- 16635468
TI  - Labor dystocia and its association with interpregnancy interval.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prevalence of labor
      dystocia and its association with interpregnancy interval. STUDY DESIGN: We
      linked the birth data for Michigan infants who were born from 1994 to 2002 with
      the hospital discharge data. The International Classification of Diseases (9th
      revision, clinical modifications, ICD-9-CM) codes that indicate labor dystocia
      were identified by a physician panel and classified as functional and mechanical
      dystocia. We estimated the prevalence of labor dystocia and used stratified and
      logistic regression analyses to evaluate labor dystocia in relation to
      interpregnancy interval, controlling for other reproductive risk factors.
      RESULTS: Overall, 20.8% of the births involved labor dystocia (11.1% functional;
      12.5% mechanical). Both functional and mechanical dystocia were more prevalent in
      first births than in subsequent births; mechanical dystocia was more prevalent in
      multiple births than in singleton births. In singleton births to multiparous
      mothers, labor dystocia was associated with the interpregnancy interval in a dose
      response fashion. Compared with an interpregnancy interval of <2 years, the
      adjusted odds ratios that was associated with interpregnancy intervals of 2 to 3,
      4 to 5, 6 to 7, 8 to 9, and 10+ years were 1.06 (95% CI, 1.04-1.08), 1.15 (95%
      CI, 1.12-1.17), 1.25 (95% CI, 1.21-1.29), 1.31 (95% CI, 1.26-1.37), and 1.50 (95%
      CI, 1.45-1.56), respectively, when we controlled for other reproductive risk
      factors. Functional dystocia was associated more strongly with interpregnancy
      interval than mechanical dystocia. CONCLUSION: Labor dystocia is common. In
      singleton births to multiparous mothers, labor dystocia increased with
      interpregnancy interval.

PMID- 16635469
TI  - Pregnancy loss after first-trimester viability in women with sickle cell trait:
      time for a reappraisal?
AB  - OBJECTIVE: The purpose of this study was to evaluate the obstetric outcomes and
      pathologic findings in women with sickle cell trait. STUDY DESIGN: In this
      retrospective case control study, pregnant women with sickle cell trait were
      studied over a 4-year period (2001-2005). The women who were delivered at > 16
      weeks of gestation were compared with a cohort group of subjects with normal
      hemoglobin levels, and the placentas were sent for pathologic evaluation.
      RESULTS: A total of 180 pregnancies were studied with a like number of control
      patients. Subjects who had sickle cell trait demonstrated shorter average
      duration of pregnancy (233 +/- 45 days vs 255 +/- 34 days; P < .001) and lower
      birth weight (2114 +/- 1093 g vs 2672 +/- 942 g; P < .001). The rate of fetal
      death was significantly higher among study group patients (3.5% vs 9.7%; P =
      .015) when compared with the control group. Additionally, in study women, acute
      ascending amniotic infection and meconium histiocytosis were noted much more
      frequently. Sickling in the intervillous space and decidual vessels that were not
      associated with artifactual change was also found among patients sickle cell
      trait. CONCLUSION: Patients with sickle cell trait appear to be at increased risk
      for fetal loss compared with women with normal hemoglobin levels, and placental
      abnormalities may play a causal role.

PMID- 16635470
TI  - Correlations of placental perfusion and PlGF protein expression in early human
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to investigate temporal correlations
      between maternal serum placenta growth factor levels and placental perfusion in
      early human pregnancies. STUDY DESIGN: Systolic umbilical artery Doppler blood
      flow velocity indices at fetal and placental insertion sites were measured
      between 7 and 22 weeks of gestation from normal singleton pregnancies. Maternal
      serum placenta growth factor levels were determined by enzyme-linked
      immunosorbent assay. RESULTS: Maternal serum placenta growth factor levels showed
      an exponential increase at approximately 14 weeks of gestation. Placenta
      perfusion, as estimated by systolic Doppler blood flow indices, significantly
      increased with gestational age (P < .0001). There was a close association between
      placenta growth factor expression levels and evidence of increased placenta
      perfusion (P < .033). CONCLUSION: The significant increase in serum placenta
      growth factor coincides with the increased perfusion of the maternal/fetal
      interface at approximately 12 to 14 weeks of gestation. Correlation of placenta
      growth factor expression and placental perfusion suggests that placenta growth
      factor may contribute to assuring adequate vascular development/function of the
      placenta early in gestation.

PMID- 16635471
TI  - Ethics, a neglected dimension of power relationships of physician leaders.
AB  - OBJECTIVE: Physician leaders in obstetrics and gynecology find themselves in
      complex power relationships with administrative subordinates, administrative
      peers, and administrative superiors. The ethical dimensions of these power
      relationships have not been examined previously. STUDY DESIGN: The authors draw
      on the work of 3 major historic figures (John Gregory, Thomas Hobbes, and
      Friedrich Hoffmann) to identify for the first time 3 major types of power
      relationships and organizational cultures. Gregorian power relationships and
      organizational cultures are characterized by shared fiduciary responsibility that
      advances the core mission of a health care organization. Hobbesian power
      relationships and organizational cultures are characterized by relentless self
      interest in a zero-sum game. Hoffmannian power relationships and organizational
      cultures are characterized by enlightened self-interest in a win-win game.
      RESULTS: The authors analyze the ethical dimensions of power relationships of
      physician leaders with subordinates, peers, and superiors and of organizational
      cultures. CONCLUSION: The authors support transformational leadership toward
      Gregorian power relationships and organizational cultures, using, when necessary,
      Hoffmannian power relationships and organizational cultures as a way station.

PMID- 16635472
TI  - The effectiveness of tension-free vaginal tape (TVT) and quality of life measured
      in women with previous urogynecologic surgery: analysis from The Netherlands TVT
      database.
AB  - OBJECTIVE: Long-term outcome of tension-free vaginal tape (TVT) in women with a
      history of surgery for urinary incontinence and/or prolapse. STUDY DESIGN:
      Prospective cohort study of 809 women. Twenty-eight teaching and 13 local
      hospitals, 54 gynecologists and urologists performed the TVTs. The Incontinence
      Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) were used
      to measure the results of the TVT procedure (preoperative at 2, 6, 12, 24, and 36
      months postoperative). According the recommendation of the International
      Continence Society, the question "Do you experience urinary leakage during
      physical activity, coughing or sneezing?" was selected from the UDI to assess
      stress urinary incontinence. RESULTS: The decrease in IIQ/UDI mean scores was
      statistically significant. The UDI scores of women with a history of previous
      prolapse and/or incontinence surgery were not statistically different to the
      scores for primary cases after 3 years follow-up (P = .193). CONCLUSION: TVT is
      effective for women with recurrent stress urinary incontinence and/or previous
      prolapse surgery.

PMID- 16635474
TI  - Five years to the Term Breech Trial: the rise and fall of a randomized controlled
      trial.

PMID- 16635477
TI  - A 96-well formatted method for exon and exon/intron boundary full sequencing of
      the CFTR gene.
AB  - Full genotypic characterization of subjects affected by cystic fibrosis (CF) is
      essential for the definition of the genotype-phenotype correlation as well as for
      the enhancement of the diagnostic and prognostic value of the genetic
      investigation. High-sensitivity diagnostic methods, capable of full scanning of
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene, are needed
      to enhance the significance of these genetic assays. A method for extensive
      sequencing of the CFTR gene was optimized. This method was applied to subjects
      clinically positive for CF and to controls from the general population of central
      Italy as well as to a single subject heterozygous for a mild mutation and with an
      uncertain diagnosis. Some points that are crucial for the optimization of the
      method emerged: a 96-well format, primer project and purification, and amplicon
      purification. The optimized method displayed a high degree of diagnostic
      sensitivity; we identified a subset of 13 CFTR mutations that greatly enhanced
      the diagnostic sensitivity of common methods of mutational analysis. A novel
      G1244R disease causing mutation, leading to a CF phenotype with pancreatic
      sufficiency but early onset of pulmonary involvement, was detected in the subject
      with an uncertain diagnosis. Some discrepancies between our results and
      previously published CFTR sequence were found.

PMID- 16635478
TI  - Influence of expressed emotion and perceived criticism on cognitive-behavioral
      therapy for social phobia.
AB  - This study examined significant others' expressed emotion (EE) and a closely
      related construct, perceived criticism, as predictors of cognitive-behavioral
      therapy outcome in a sample of 40 patients with social phobia (social anxiety
      disorder). Patients enrolled in group therapy for social phobia completed pre-
      and post-treatment questionnaire measures of perceived criticism and anxious and
      depressive symptoms. Designated significant others were assessed for the
      components of high EE (criticism, hostility and emotional overinvolvement) using
      the Camberwell Family Interview. It was hypothesized that these high-EE
      components and patients' perceived criticism would be associated with poorer
      treatment outcome, and results ran counter to these expectations. Controlling for
      initial social phobia severity, lower levels of perceived criticism predicted
      treatment dropout. There was also a nonsignificant trend for participants with a
      significant other rated as high in emotional overinvolvement to show less change
      on a composite symptom measure. Findings from this study suggest that close
      relationships impact the outcome of cognitive-behavioral interventions for social
      phobia.

PMID- 16635479
TI  - Worry and rumination: differential associations with anxious and depressive
      symptoms and coping behavior.
AB  - Worry and rumination are closely allied cognitive processes that impact on the
      experience of anxious and depressive symptoms. Using a prospective design, this
      study examined overlapping and distinct features of worry and rumination in
      relation to symptoms and coping behavior in a nonclinical sample of Singaporean
      college students. Worry and rumination were highly correlated, but they retained
      distinct components that predicted anxious and depressive symptoms differentially
      within and across time. Specifically, worry was uniquely associated with anxious
      and depressive symptoms whereas rumination was uniquely related to depression. In
      comparison to rumination, worry emerged as the dominant cognitive vulnerability
      factor that predicted increments in symptoms over time. With regards to coping
      behavior, low perceived coping effectiveness partially mediated the relation
      between worry and increases in anxiety and depression. Conversely, rumination
      uniquely predicted higher disengagement from problems, which resulted in further
      exacerbation of depressive mood. These results demonstrated not only the distinct
      features of worry and rumination on coping behavior, but also the different
      coping pathways by which they differentially impact on subsequent symptoms.

PMID- 16635480
TI  - P2X7 receptor immunoreactive profile confined to resting and activated microglia
      in the epileptic brain.
AB  - The purpose of this study was to identify the CNS cellular constituent
      immunoreactive for specific P2X7 receptor antiserum in the kainate-induced
      seizure and non-seizure rat brain. Analysis of P2X7 immunocytochemistry (ICC)
      revealed small immunoreactive cells with processes showing distinct morphological
      changes as seizures progressed in time. These morphological changes were
      reminiscent of reactive glia during CNS injury. In order to determine the
      identity of this non-neuronal cellular constituent, we employed dual ICC
      techniques using sequential antibody incubations and reacted the sections with
      contrasting chromagens. Specific glial markers tested in the series included Iba1
      (microglia), COX-1 (microglia), and GFAP (astroglia). Results of this study
      revealed distinct colocalization when sections immunostained for P2X7 were dual
      immunostained with antisera specific for microglia (Iba1, COX-1). In contrast, no
      colocalization was evident when sections were dual immunostained with P2X7 and
      GFAP, an astrocytic marker. In the latter experiment, dual ICC revealed two
      distinct cell populations with contrasting color demonstrating a population of
      distinct GFAP immunopositive cells and a population of distinct P2X7
      immunopositive cells. We conclude that P2X7 antiserum used in this study is
      specific for and identifies microglia in rat and that there exists a timeline of
      progressive changes in microglia morphology that can be demonstrated following
      kainate-induced seizures. In addition, the morphological changes in microglia
      following seizure induction that can be identified with P2X7 antisera or with
      antisera specific for microglia suggest a neuroinflammatory milieu in areas of
      CNS seizure activity.

PMID- 16635481
TI  - MAP kinase regulation of IP10/CXCL10 chemokine gene expression in microglial
      cells.
AB  - Interferongamma inducible protein-10 (IP10 or CXCL10), a Th-1 affiliated
      chemokine, is expressed by activated glial cells and may contribute to the
      trafficking of immune cells in the inflamed central nervous system. This study
      examines the regulation of the expression of this chemokine in cultured
      microglial cells focusing on the roles of mitogen-activated protein (MAP) kinase
      cascades. Exposure of a mouse microglial cell line, BV-2, to lipopolysaccharide
      (LPS) and IFNgamma led to an induction of IP10 mRNA and protein as determined by
      RT-PCR and ELISA, respectively. This induction was suppressed by pharmacological
      inhibitors of p38 MAPK (i.e., SB203580) and c-Jun N-terminal kinase (JNK,
      SP600125), suggesting the involvement of the two kinases in IP10 expression. LPS
      also induced the activity of an IP10 promoter reporter (luciferase) construct
      transfected into BV-2 cells in a MAP kinase- and NFkappaB-dependent manner. The
      use of deletion constructs revealed that the kinase-targeted sequences were
      within the region between -533 bp and -332 bp upstream of the transcriptional
      start site. Co-transfection of IP10 luciferase with the active forms of the
      upstream kinases in the MAP kinase cascades, i.e., MAPK kinase-3 (MKK3), MKK6
      (the immediately upstream activators of p38 kinase) and a MAP3K, i.e., TGFbeta
      activated kinase-1 (TAK1), produced a marked stimulation of the promoter
      activity. The results of this study indicate that the MAP kinase cascades
      prominently regulate IP10 gene expression in microglial cells.

PMID- 16635482
TI  - Small heat shock proteins inhibit amyloid-beta protein aggregation and
      cerebrovascular amyloid-beta protein toxicity.
AB  - Small heat shock proteins Hsp20 and HspB2/B3 co-localize with Abeta deposition in
      senile plaques and cerebral amyloid angiopathy in Alzheimer's disease brains,
      respectively. It was the aim of our study to investigate if these and other sHsps
      bind to wild-type Abeta1-42 or the more toxic Abeta1-40 carrying the 'Dutch'
      mutation (22Glu-->Gln) (D-Abeta1-40), affect Abeta aggregation and thereby
      influence Abeta cytotoxicity. Binding affinity between sHsps and Abeta was
      investigated by surface plasmon resonance. Abeta aggregation was studied by using
      circular dichroism spectroscopy and electron microscopy. Furthermore, we used
      cultured cerebrovascular cells to investigate the effects of sHsps on Abeta
      mediated cytotoxicity. Hsp20, Hsp27 and alphaB-crystallin, but not HspB2/B3,
      bound to Abeta (both D-Abeta1-40 and Abeta1-42) and reduced or completely
      inhibited aggregation of D-Abeta1-40 into mature fibrils but did not affect
      Abeta1-42 aggregation. Furthermore, these sHsps were effective inhibitors of the
      cerebrovascular toxicity of Abeta (both D-Abeta1-40 and Abeta1-42) in vitro.
      Binding affinity of the sHsps to D-Abeta1-40 correlated to the degree of
      inhibition of Abeta-mediated cytotoxicity and the potential to reduce Abeta beta
      sheet and fibril formation. With Abeta1-42, a similar correlation between binding
      affinity and cytotoxicity was observed, but not with its aggregation state. In
      conclusion, sHsps may regulate Abeta aggregation and serve as antagonists of the
      biological action of Abeta, but the extent of their interaction depends on the
      type of sHsp and Abeta peptide.

PMID- 16635483
TI  - Vascular neutral endopeptidase inhibition improves endothelial function and
      reduces intimal hyperplasia.
AB  - OBJECTIVE: Neutral endopeptidase (NEP, EC 3.4.24.11) metabolises endogenous
      vasoactive peptides that may protect against atherogenesis. Since NEP is found in
      the adventitia of arteries, we investigated the anti-atherogenic effects of
      chronic adventitial NEP inhibition. METHODS: Intimal hyperplasia of rabbit
      carotid arteries was induced by placement of soft, non-occlusive, peri-arterial
      silastic collars. NEP localisation was studied with autoradiography 7 and 14 days
      after collar placement. Vascular NEP was inhibited in vivo by local superfusion
      of one collared carotid artery with Candoxatrilat (50 pmol/h), for 7 days (n =
      7). The contralateral collar was filled with saline vehicle. After 7 days, ring
      segments of collared and normal (proximal to the collar) arteries were obtained
      and in vitro functional measurements, immunohistochemical determination of the
      pro-atherogenic factor plasminogen activator inhibitor-1 (PAI-1), localization of
      macrophages and morphometric analyses were carried out. RESULTS: Vascular NEP
      radiolabelled substrate binding, mainly in the media, was increased by
      approximately 50% after 7 days (n = 5; p < 0.05) and by approximately 300% after
      14 days of collar placement (n = 5; p < 0.05). Compared with normal artery
      segments from the same animal, vehicle-filled collared sections displayed
      significantly impaired vasorelaxation to acetylcholine (endothelium-independent
      vasodilatation was preserved), increased PAI-1 immunostaining, macrophage
      accumulation and intimal thickening. In Candoxatrilat-treated collared arteries,
      vasorelaxation to acetylcholine was improved, along with reductions in PAI-1
      levels, macrophage numbers and intimal area (all p < 0.05). CONCLUSION: Enhancing
      the activity of local, endogenous peptides by adventitial inhibition of vascular
      NEP may protect against early atherogenesis. This is of particular relevance to
      using adventitial therapies to prevent intimal hyperplasia leading to restenosis.

PMID- 16635484
TI  - Incorporation of phytosterols in human keratinocytes. Consequences on UVA-induced
      lipid peroxidation and calcium ionophore-induced prostaglandin release.
AB  - We have designed experimental conditions allowing the replacement of 50% of
      cholesterol of human keratinocytes (SVK14 line) with sitosterol or stigmasterol
      without affecting cellular viability. We have investigated the influence of
      incorporating phytosterol on the ultraviolet-A-induced formation of lipid
      peroxidation products (thiobarbituric reactive substances (TBARS)) in these
      cells. Our results show that ultraviolet-A-induced lipid peroxidation depends on
      the nature of the phytosterol. Sitosterol induces a significant decrease (-30%)
      of TBARS relative to the control whereas stigmasterol markedly increases lipid
      peroxidation (+70%). We have also studied the effect of plant sterols on
      prostaglandin release by using the Ca(2+) ionophore A23187 as an in vitro model
      of the inflammation induced by UVA radiation. We show that in the presence of 50%
      of phytosterol (particularly stigmasterol), the release of prostaglandin (6
      ketoPG(1alpha), PGE(2)) is increased compared to untreated cells. This pro
      inflammatory effect of phytosterols is correlated with a loss of the regulation
      of the intracellular Ca(2+) concentration.

PMID- 16635485
TI  - Zeta-sarcoglycan is a functional homologue of gamma-sarcoglycan in the formation
      of the sarcoglycan complex.
AB  - The sarcoglycans (SGs), transmembrane components of the dystrophin-associated
      glycoprotein complex, are stable and functional only when they assemble into a
      tetrameric complex in muscle cells. A defect in any one of the four SG members
      disrupts the entire SG complex (SGC) and causes limb-girdle muscular dystrophy.
      zeta-SG has been recently found as a transmembrane protein homologous to gamma-SG
      and delta-SG. To characterize zeta-SG in complex formation, we co-transfected
      expression vectors encoding all six SGs (alpha-, beta-, gamma-, delta-, epsilon-
      and zeta-SG) and dystroglycan into Chinese hamster ovary cells.
      Immunoprecipitation analysis showed that zeta-SG or gamma-SG formed a SGC with
      beta-SG and delta-SG plus alpha-SG or epsilon-SG, revealing that zeta-SG can form
      two types of SGCs (alpha-beta-zeta-delta or epsilon-beta-zeta-delta). This result
      indicates the functional resemblance of zeta-SG to gamma-SG rather than delta-SG,
      although phylogenetic analysis suggests that zeta-SG is evolutionally closer to
      delta-SG than to gamma-SG. Reverse transcription (RT)-PCR showed that the
      expression pattern of the transcript was almost the reciprocal of that of gamma
      SG in various mouse tissues and that the zeta-SG transcript was especially
      abundant in the brain, suggesting that zeta-SG might play a particular role in
      the central nervous system.

PMID- 16635486
TI  - Molecular identification and characterisation of the glycine transporter (GLYT1)
      and the glutamine/glutamate transporter (ASCT2) in the rat lens.
AB  - Glutathione (GSH) is an essential antioxidant required for the maintenance of
      lens transparency. In the lens, GSH is maintained at unusually high
      concentrations as a result of direct GSH uptake and/or intracellular de novo
      synthesis from its precursor amino acids; cysteine, glycine and
      glutamine/glutamate. With increasing age, the levels of GSH, particularly in the
      core of the lens, are significantly reduced. It has been proposed that
      alterations in the transport of GSH and/or its precursor amino acids may
      contribute to the changes in GSH levels in older lenses. As considerable
      uncertainty exists about the molecular identity of GSH transporters in the lens,
      we have focused on identifying transporters involved in the uptake of the
      precursor amino acids required for GSH synthesis. Previously, we identified an
      uptake system for cyst(e)ine mediated by the Xc(-) exchanger and the Excitatory
      Amino Acid Transporters (EAATs) in the rat lens. In this current study, we have
      identified and localised additional uptake systems that contribute to GSH
      synthesis. Transcripts for GLYT1 (glycine transporter) and ASCT2
      (glutamine/glutamate transporter) were detected in rat lens fiber cells using the
      reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis
      confirmed the expression of both GLYT1 and ASCT2 at the protein level.
      Immunocytochemistry revealed GLYT1 expression to be restricted to cortical
      regions of the lens. Labelling was predominantly cytoplasmic with some labelling
      of the membrane. In contrast, ASCT2 was expressed throughout the lens extending
      from the outer cortex through to the core. In the outer cortex, ASCT2 expression
      was predominantly cytoplasmic. However, with deeper distance into the lens,
      labelling became more membraneous indicating insertion of ASCT2 into the
      membranes of mature fiber cells of the lens core. The molecular identification
      and localisation of GLYT1 and ASCT2 in the lens suggests that these transporters
      may be responsible for the uptake of the precursor amino acids, glycine and
      glutamine, which are involved in GSH synthesis. Moreover, the presence of ASCT2
      in the centre of the lens raises the possibility that ASCT2 may work with the Xc(
      ) exchanger to accumulate cysteine where it can potentially act as a low
      molecular mass antioxidant.

PMID- 16635487
TI  - A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: an
      additional tool for characterising intracellular mis-localisation leading to
      increased AMD susceptibility.
AB  - An artificial mutant Ala25Ser precursor cystatin C was created to help elucidate
      the cause of intracellular mis-localisation of the biochemically related variant
      B (Ala25Thr) precursor cystatin C to the mitochondria. Homozygotes of variant B
      precursor cystatin C were reported to carry an increased susceptibility to
      developing the exudative form of AMD. Ala25Ser precursor cystatin C shows a dual
      distribution to the Golgi apparatus and to the mitochondria. This localisation is
      thus intermediary between that of wild-type cystatin C (targeted to ER/Golgi
      compartment) and that of variant B precursor cystatin C. Furthermore, the level
      of secretion of Ala25Ser cystatin C by RPE cells is intermediary between wild
      type and variant B cystatin C. Ala25Ser precursor cystatin C thus represents a
      biochemical intermediate between the wild type and the AMD-associated cystatin C
      and as such, is a novel tool for the investigation of the mechanism of
      intracellular mis-localisation of variant B cystatin C. Our findings further
      support the hypothesis that substitution of the alanine residue in the
      penultimate position of precursor cystatin C signal sequence with a less
      hydrophobic amino acid residue, such as threonine (as in variant B cystatin C) or
      serine is sufficient to impair the intracellular trafficking and processing of
      the protein.

PMID- 16635488
TI  - Inhibiting the transient choroidal thickening response using the nitric oxide
      synthase inhibitor l-NAME prevents the ameliorative effects of visual experience
      on ocular growth in two different visual paradigms.
AB  - It is generally accepted that the increase in choroidal thickness in response to
      myopic defocus in chicks acts to move the retina towards the image plane. It may
      also constitute part of the signal cascade in the visual regulation of eye
      growth. To test this, we used the nitric oxide synthase inhibitor l-NAME to
      inhibit the defocus induced choroidal thickening under two different visual
      conditions, and looked at the effects on ocular growth rate. Exp. 1:
      Deprivation/Vision: chicks were monocularly deprived of form vision with
      translucent diffusers from day 6 to day 9. In the middle of each day the
      diffusers were removed for 2 h. One group received an intravitreal injection of
      30 microl l-NAME (16 micromole; n=12) prior to the vision, a second group
      received injections of physiological saline (n=11). Exp. 2: Recovery/Vision:
      chicks were made myopic by form deprivation from day 6 to day 10. On days 11 to
      14 the diffusers were removed for 2 h per day for 4 days to allow eyes to
      "recover" from the myopia. One group received an injection of l-NAME prior to
      vision (n=8), the other saline (n=6). Refractive errors were measured with a
      refractometer at the start (days 6 and 11) and end (days 10 and 15, respectively)
      of both experiments. Ocular dimensions were measured with high frequency A-scan
      ultrasonography at the start and end, and on the third experimental day
      immediately before and after the period of vision. Choroidal retinoic acid
      synthesis was measured by HPLC. Finally, NO production and scleral proteoglycan
      synthesis were measured in eyes wearing positive lenses 6 and 24h after an
      injection of l-NAME. l-NAME prevented the transient vision-induced choroidal
      thickening in both experiments. Furthermore, l-NAME inhibited the protective
      effect of brief daily vision: eyes became significantly more myopic than saline
      controls (exp. 1: -9 D vs -2.7D; exp. 2: -0.9 D vs +4.3 D; p<0.005 for both) and
      grew faster (change in lens-sclera: exp. 1: 295 vs 158 microm; exp. 2: 147 vs 39
      microm; p<0.05 for both). Notably, l-NAME inhibited the growth of the anterior
      chamber (exp. 1: 88 vs 185 microm; exp. 2: 147 vs 254 microm; p<0.01 for both).
      Injections of l-NAME after the periods of vision had no effect on growth at the
      back of the eye, but still had an inhibitory effect on the anterior chamber.
      Retinoic acid levels in the drug-injected choroids were significantly decreased
      compared to controls. In eyes responding to positive lenses, l-NAME inhibited NO
      synthesis and disinhibited scleral glycosaminoglycan synthesis 6h after the
      injection. In summary, preventing the transient vision-induced increases in
      choroidal thickness altered ocular growth rate in a consistent manner under two
      different visual conditions, in both preventing the vision-induced reduction in
      growth rate. This supports the hypothesis that visually-induced changes in
      choroidal thickness play a role in the visual regulation of ocular growth.

PMID- 16635489
TI  - Bright cyclic light rearing-mediated retinal protection against damaging light
      exposure in adrenalectomized mice.
AB  - Previous studies have shown that albino rats and mice raised in bright cyclic
      light are protected from light-induced retinal damage. We tested if the stress
      response mediated by the adrenal grand is involved in the initiation of this
      neuroprotective phenomenon. Balb/c mice that were adrenalectomized (Adrex) or
      sham operated at 28 days of age were kept under dim (5 lux) or bright (400 lux)
      cyclic light (12h on/off) for 2 weeks. Thereafter, their electroretinogram (ERG),
      outer nuclear layer (ONL) thickness and area, and plasma corticosterone levels
      were measured in animals with (dim+light and bright+light groups) and without
      (dim and bright groups) damaging light exposure (3000 lux for 24 h). In the
      dim+light group, a- and b-wave amplitudes and the ONL thicknesses and areas were
      significantly higher in the Adrex animals than the sham animals, indicating that
      adrenalectomy itself yielded retinal protection. In the Adrex animals, the ONL
      areas were significantly larger in the bright+light group than the dim+light
      group, indicating that bright cyclic light rearing yielded further retinal
      tolerance, even in the absence of the adrenal gland. In sham animals, the plasma
      corticosterone concentration did not change between the dim and the light groups.
      Accordingly, glucocorticoid secreted from the adrenal gland is not likely to be
      required for the mechanisms of the light-adaptation neuroprotection phenomenon in
      mice.

PMID- 16635490
TI  - Comparative assessment of distribution of blackcurrant anthocyanins in rabbit and
      rat ocular tissues.
AB  - Anthocyanins (ACs) are phenolic compounds that are distributed widely in fruits
      and vegetables. Although consumption of these compounds has been shown to improve
      visual function, the distribution of ACs in ocular tissue has not been examined
      in detail. The aim of this study was therefore to evaluate the ocular
      distribution of blackcurrant anthocyanins (BCAs) in rats and rabbits after oral,
      intravenous (i.v.) and intraperitoneal (i.p.) administration. Identification and
      quantification of ACs were carried out using high-performance liquid
      chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) and high
      performance liquid chromatography (HPLC) with UV-visible detection, respectively.
      BCAs were identified in the plasma and whole eye after oral and i.p.
      administration in rats. No other peaks were detected in either plasma or ocular
      tissues after administration when the absorbance of the eluate was monitored at
      520 nm. This finding indicates that intact forms of ACs were present in rats
      after administration of BCA. In rats given i.p. administration, the concentration
      of total ACs in the whole eye and some ocular tissues was higher than that
      measured in plasma. These results suggested that ACs detected in the ocular
      tissues were not due to residual blood. Following i.v. administration in rabbits,
      four ACs were identified in the plasma and several ocular tissues including the
      aqueous humor, cornea, sclera, choroid, ciliary body, iris and retina. A small
      amount of ACs was also detected in the vitreous and lens. In conclusion, this
      study demonstrated that BCAs were absorbed and distributed in ocular tissues as
      intact forms. Our data show clearly that intact forms of BCAs pass thorough the
      blood-aqueous barrier and blood-retinal barrier in both rats and rabbits.

PMID- 16635491
TI  - Solute-solvent interactions in micellar liquid chromatography. Characterization
      of hybrid micellar systems of sodium dodecyl sulfate-pentanol.
AB  - The solvation parameter model has been applied to the characterization of hybrid
      micellar chromatographic systems with mixtures of sodium dodecyl sulfate (SDS)
      and pentanol as mobile phases. Retention factors for 22 compounds in two groups,
      phenethylamines and antihistamines, were used for the characterization of the
      systems after the calculation of their Abraham descriptors. Three equations were
      developed as multiple linear regressions using Abraham descriptors and
      properties, such as log Poct and polar surface area to correlate the retention
      factors. A group of 30 data points was used as an independent test set to assess
      the predictive capability of the equations. Micellar chromatographic systems were
      compared against other separation systems using principal components analysis.
      Conventional RPLC chromatography using mobile phases with high amounts of organic
      solvents are close to the micellar mobile phases that only use small amounts of
      alcohol.

PMID- 16635492
TI  - Selenium speciation by high-performance anion-exchange chromatography-post-column
      UV irradiation coupled with atomic fluorescence spectrometry.
AB  - A technique for the speciation of selenomethylcysteine (SeMeCys), selenocystine
      (SeCys), selenite [Se(IV)] and selenomethionine (SeMet) was established in this
      paper using high-performance anion-exchange chromatography coupled with atomic
      fluorescence spectrometry (HPAEC-AFS). Analytes were separated on an AminoPac
      PA10 column and then digested by on-line ultraviolet (UV) irradiation, which
      destroyed organic compound structure. Hydride generation was used as an available
      sample introduction technique for atomic fluorescence detection. The detection
      limits of four compounds were 1-5 microg/L (250 microL injection, 10 times of the
      baseline noise). The relative standard deviations (RSDs), calculated from seven
      consecutive injections of 100 microg/L standard mixtures, were from 2 to 4%.
      Selenious yeast tablet, which had been proposed as selenium supplement, and human
      urine collected from a volunteer were analyzed. Good spiked recoveries from 86 to
      103% were obtained.

PMID- 16635493
TI  - Probing the interaction of solvents with the stationary phase of C18 high
      performance liquid chromatographic column material by variable-temperature
      dependent 129Xe nuclear magnetic resonance spectroscopy.
AB  - VT (129)Xe NMR was applied to probe the interactions of solvents having different
      polarity indices with the stationary phase of a RP-C18 HPLC column material. It
      was observed that the highly polar ethylene glycol molecules do not mix with the
      alkyl chains of the RP-C18 stationary phase and the solvent is unable to enter
      the pores and the spaces between the particles. Three phases in this sample are
      defined as stationary/xenon phase, xenon gas phase (in the pores and the spaces
      between the particles) and ethylene glycol/xenon phase. In contrast to ethylene
      glycol, the nonpolar solvent cyclohexane was observed to be well mixed with the
      RP-C18 stationary phase. The capillary rise effect allows the solvent to enter
      the pores and the spaces between the particles. Two phases in this sample are
      defined as stationary/cyclohexane/xenon phase and cyclohexane/xenon phases. The
      properties of ethyl acetate are between those of ethylene glycol and cyclohexane.
      The (129)Xe NMR results show that the rational reversed phases should be
      conditioned from highly solvating to more polar solvents to remove the trapped
      air. The (129)Xe NMR results also show that pure stationary phase exists only
      when a highly polar solvent is used in reversed-phase chromatography. For a
      solvent with lower polarity, a stationary/solvent phase actually forms. This,
      together with the mobile phase, determines the selective factor for separating
      mixtures.

PMID- 16635494
TI  - Single subject controlled experiments in aphasia: the science and the state of
      the science.
AB  - This paper discusses the use of single subject controlled experimental designs
      for investigating the effects of treatment for aphasia. A brief historical
      perspective is presented, followed by discussions of the advantages and
      disadvantages of single subject and group approaches, the basic requirements of
      single subject experimental research, and crucial considerations in design
      selection. In the final sections, results of reviews of published single subject
      controlled experiments are discussed, with emphasis on internal validity issues,
      the number of participants enrolled in published studies, operational
      specification of the dependent and independent variables, and reliability of
      measurement. LEARNING OUTCOMES: As a result of reading this paper, the
      participant will: (1) understand the mechanisms required for demonstration of
      internal and external validity using single subject controlled experimental
      designs, (2) become familiar with the basic requirements of single subject
      controlled experimental research, (3) understand the types of single subject
      controlled experimental designs that are the most appropriate for studying the
      effects of treatment for aphasia, and (4) become familiar with trends in the
      published aphasia treatment literature in which single subject controlled
      experimental designs have been used.

PMID- 16635495
TI  - Cognitive changes in early MS: a call for a common framework.
AB  - Cognitive dysfunction is among the main symptoms of multiple sclerosis (MS) and
      adversely affects patients' quality of life. The occurrence of cognitive
      impairment early in the disease process raises crucial issues related to
      definition of the impairment and its magnitude as well as to the tools applied to
      the assessment. To date there is little evidence concerning the reliability and
      validity of cognitive measures in early MS and their predictive long-term role.
      As MS is a complex disease, multidimensional approaches should be further
      developed and validated to study the cognitive sphere in the early stages of the
      disease. Considering that none of the available tests performed in isolation is
      able to provide a complete picture of the cognitive impairment in early MS, this
      calls for the definition of phase duration, impairment and tools appropriate for
      use by clinicians and researches. The present review proposes a framework aimed
      to help neurologists in approaching cognitive impairment in early MS and
      stimulate discussions and evaluations of the suggested recommendations.

PMID- 16635496
TI  - Ganoderiol F, a ganoderma triterpene, induces senescence in hepatoma HepG2 cells.
AB  - Ganoderiol F (GolF), a tetracyclic triterpene, was isolated from Ganoderma
      amboinense and found to induce senescence of cancer cell lines. GolF induced
      growth arrest of cancer cell lines HepG2, Huh7 and K562, but exerted much less
      effect in hepatoma Hep3B cells and normal lung fibroblast MRC5 cells, and no
      effect on peripheral blood mononuclear cells. GolF treatment of the cancer cells,
      with the exception of Hep3B, resulted in prompt inhibition of DNA synthesis and
      arrest of cell progression cycle in G1 phase. Short-term exposure of HepG2 cells
      to GolF temporarily arrested progression of the cell cycle; cell growth was
      recovered if the drug was withdrawn from the medium after a 24-h exposure. After
      18 days of continuous treatment of HepG2 cells with 30 muM GolF, over 50% of
      cells were found to be enlarged and flattened, and were beta-galactosidase
      positive phenotypes of senescent cells. GolF was found to inhibit activity of
      topoisomerases in vitro, which may contribute to the inhibition of cellular DNA
      synthesis. Activation of the mitogen-activated protein kinase EKR and up
      regulation of cyclin-dependent kinase inhibitor p16 were found in early stages of
      GolF treatment and were presumed to cause cell-cycle arrest and trigger premature
      senescence of HepG2 cells. The growth-arrest and senescence induction capability
      on cancer cells suggest anticancer potential of GolF.

PMID- 16635497
TI  - Calponin and caldesmon cellular domains in reacting microvessels following
      traumatic brain injury.
AB  - Calponin (Cp) and caldesmon (Cd) are actin-binding proteins involved in the
      regulation of smooth muscle (SM) tone during blood vessel contraction. While in
      vitro studies have reported modifications of these proteins during vessel
      contractility, their role in vivo remains unclear. Traumatic brain injury (TBI)
      causes disruption of cerebral microvascular tone, leading to sustained
      contractility in reacting microvessels and cerebral hypoperfusion. This study
      aimed to determine the spatial and temporal expressions of Cp and Cd in rat
      cerebral cortical and hippocampal microvessels post-TBI. Reacting microvessels
      were analyzed in control, 4, 24, and 48 h post-injury. Single and double
      immunocytochemical techniques together with semiquantitative analyses revealed a
      Cp upregulation in SM at all time frames post-TBI; with the protein migrating
      from SM cytosol to the vicinity of the cell membrane. Similarly, Cd
      immunoreactivity significantly increased in both SM and endothelial cells (En).
      However, while Cp and Cd in SM remained elevated, their levels in En returned to
      normal at 48 h post-TBI. The results suggest that Cp and Cd levels increase while
      compartmentalizing to specific subcellular domains. These changes are temporally
      associated with modifications in the cytoskeleton and contractile apparatus of SM
      and En during blood vessel contractility. Furthermore, these changes may underlie
      the state of sustained contractility and hypoperfusion observed in reacting
      microvessels after TBI.

PMID- 16635498
TI  - Focal putamen lesions impair learning in rule-based, but not information
      integration categorization tasks.
AB  - Previous research on the role of the basal ganglia in category learning has
      focused on patients with Parkinson's and Huntington's disease, neurodegenerative
      diseases frequently accompanied by additional cortical pathology. The goal of the
      present study was to extend this work to patients with basal ganglia lesions due
      to stroke, asking if similar changes in performance would be observed in patients
      with more focal pathology. Patients with basal ganglia lesions centered in the
      putamen (6 left side, 1 right side) were tested on rule-based and information
      integration visual categorization tasks. In rule-based tasks, it is assumed that
      participants can learn the category structures through an explicit reasoning
      process. In information-integration tasks, optimal performance requires the
      integration of information from two or more stimulus components, and participants
      are typically unaware of the category rules. Consistent with previous studies
      involving patients with degenerative disorders of the basal ganglia, the stroke
      patients were impaired on the rule-based task, and quantitative, model-based
      analyses indicate that this deficit was due to the inefficient application of
      decision strategies. In contrast, the patients were unimpaired on the information
      integration task. This pattern of results provides converging evidence supporting
      a role of the basal ganglia and, in particular, the putamen in rule-based
      category learning.

PMID- 16635499
TI  - Synthesis of putative metabolites of 1alpha,25-dihydroxy-2beta-(3
      hydroxypropoxy)vitamin D(3) (ED-71).
AB  - 1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of
      active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under
      phase III clinical trials in Japan for the treatment of osteoporosis and bone
      fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A
      ring, it is recognized that the metabolic pathway of ED-71 might be more
      complicated than 1,25(OH)(2)D(3) because of metabolism at the 2beta-position
      substituent in addition to the inherent metabolism of the side chain. To clarify
      the metabolism of hydroxypropoxy substituent of the 2beta-positon and a
      combination of metabolism between side chain and 2beta-positon, four putative
      metabolites of ED-71 have been prepared as authentic samples. The metabolites at
      the 2beta-positon, the methyl ester derivative considered as an ester standard of
      the oxidized metabolite and the tetraol derivative as the truncated metabolite
      were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The
      combination metabolites between side chain and 2beta-positon, the 24(S)- and
      24(R)-pentaols were synthesized using Trost's convergent method.

PMID- 16635500
TI  - Biochemical and biological activities of the venom of the Chinese pitviper
      Zhaoermia mangshanensis, with the complete amino acid sequence and phylogenetic
      analysis of a novel Arg49 phospholipase A2 myotoxin.
AB  - Zhaoermia mangshanensis (formerly Trimeresurus mangshanensis, Ermia
      mangshanensis) represents a monotypic genus of pitviper known only from Mt Mang
      in China's Hunan Province, and is among the largest and most spectacular of Asian
      venomous snakes. The venom of Zhaoermia exhibits high coagulant activity on
      bovine and human fibrinogen and human plasma, high phosphodiesterase and arginine
      ester hydrolytic activity, and moderate to low l-amino acid oxidase, kallikrein,
      caseinolytic, phospholipase A(2) (PLA(2)), haemorrhagic and myotoxic activities.
      The approximate i.p. LD(50) of the venom in mice was estimated to be 4 mg/kg. We
      purified the major toxin of Zhaoermia venom by gel-filtration, cation-exchange
      chromatography and HPLC. The toxin, a homodimer with an experimental monomeric
      mass of 13,972 Da, induced edema and myonecrosis in mice, but was devoid of
      detectable PLA(2) catalytic activity. Its complete amino acid sequence is
      composed of 121 amino acid residues cross-linked by seven disulfide bridges, and
      shows more than 80% identity to two Lys49-PLA(2)s from distantly related Asian
      pitvipers, Protobothrops mucrosquamatus and Calloselasma rhodostoma. Phylogenetic
      analysis of the novel toxin, zhaoermiatoxin, confirmed that it is rooted within a
      comprehensive sample of Lys49-PLA(2)s despite having an arginine residue in
      position 49, suggesting a secondary Lys49-->Arg substitution which did not alter
      the catalytic inactivity of the molecule.

PMID- 16635501
TI  - Peptide profiling by matrix-assisted laser desorption/ionisation time-of-flight
      mass spectrometry of the Lasiodora parahybana tarantula venom gland.
AB  - In order to establish a venom fingerprint and a peptide profile of the Lasiodora
      parahybana tarantula venom gland, we used conventional methods such as reversed
      phase liquid chromatography coupled to an electrospray-ionisation hybrid
      quadrupole time of flight mass spectrometer (LC/ESI-QqTOFMS), matrix-assisted
      laser desorption/ionization time-of-flight-MS (MALDI-TOFMS) and direct study of
      L. parahybana venom by nanospray-ionization QqTOFMS (nanoESI-QqTOFMS) and a new
      technology for the direct analysis of fresh tissues using MALDI-TOFMS. The
      analysis of the crude venom allowed the characterization of specific juvenile and
      adult biomarkers. In situ MALDI analysis of L. parahybana venom gland sections
      revealed different peptide expression levels all along the gland and non
      processed peptide precursors, demonstrating the power of the method for the
      dynamic investigation of peptide evolution in the venom gland of spiders.

PMID- 16635502
TI  - Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus
      associated ERK-2 kinase.
AB  - L-domain-containing proteins from animal retroviruses play a critical role in the
      recruitment of the host cell endocytic machinery that is required for
      retroviruses budding. We recently demonstrated that phosphorylation of the
      p6(gag) protein containing the L-domain of the human immunodeficiency virus type
      1 regulates viral assembly and budding. Here, we investigated whether or not the
      L-domain-containing protein from another human retrovirus, namely the matrix
      protein of the human T-cell leukemia virus type 1, that contains the canonical
      PTAP and PPPY L-domain motifs, shares similar functional properties. We found
      that MA is phosphorylated at several sites. We identified one phosphorylated
      amino acid in the HTLV-1 MA protein as being S105, located in the close vicinity
      to the L-domain sequence. S105 phosphorylation was found to be mediated by the
      cellular kinase ERK-2 that is incorporated within HTLV-1 virus particles in an
      active form. Mutation of the ERK-2 target S105 residue into an alanine was found
      to decrease viral release and budding efficiency of the HTLV-1(ACH) molecular
      clone from transfected cells. Our data thus support the postulate that
      phosphorylation of retroviral L-domain proteins is a common feature to
      retroviruses that participates in the regulation of viral budding.

PMID- 16635503
TI  - Aerobic degradation of acid orange 7 in a vertical-flow constructed wetland.
AB  - Biological, aerobic degradation of an azo dye and of the resultant, recalcitrant,
      aromatic amines in a constructed wetland (CW) was demonstrated for the first
      time. A vertical-flow CW, planted with Phragmites sp. was fed with 127 mgl(-1) of
      acid orange 7 (AO7) at hydraulic loads of 28, 40, 53 and 108 l m(-2) day(-1).
      Color removal efficiencies of up to 99% clearly demonstrate cleavage of the azo
      bond, also confirmed by the similar AO7 removal and SO(4)(2-) release rates
      revealing that adsorption onto the matrix was constant. The positive redox
      potential at the outlet demonstrates that aerobic conditions were present.
      Chemical oxygen demand and total organic carbon removal efficiencies of up to 93%
      were also indicative of AO7mineralization. The degradation of sulfanilic acid was
      confirmed by the presence of NO(3)(-), SO(4)(2-) and secondary metabolites, which
      suggest at least two degradation pathways leading to a common compound, 3
      oxoadipate.

PMID- 16635504
TI  - Implications of sequential use of UV and ozone for drinking water quality.
AB  - The formation of bromate levels exceeding the drinking water standard of 10
      microg L-1 may impose the reduction of ozone doses used in the treatment of
      drinking water. This paper illustrates the procedure of evaluating the use of
      reduced ozone doses while implementing an additional UV disinfection step for an
      actual drinking water treatment plant. Ozonation was performed at low ozone doses
      in bench-scale experiments with a pretreated river water from the Paris area
      (France). At the low ozone dose of 0.5 mg L-1, bromate formation could be kept
      below 0.4 microg L-1, while inactivation of vegetative bacteria and UV-resistant
      viruses was calculated to exceed 5 log units, and a substantial decoloration (31%
      of the absorption at lambda=254 nm) was achieved. Based on the measured transient
      ozone and OH radical concentrations, the oxidation of micropollutants was
      calculated. Fast reacting micropollutants containing phenol, amine or double bond
      moieties, such as sulfamethoxazole, diclofenac and 17-alpha-ethinylestradiol,
      were completely oxidized. Slow-reacting synthetic micropollutants, e.g.,
      atrazine, iopromide and methyl tertiary butyl ether (MTBE), were oxidized by only
      20%, 20% and 10%, respectively, and the taste and odor compounds 2
      methylisoborneol (MIB) and geosmin by 40% and 50%, respectively. The addition of
      an UV treatment step to the existing treatment train, which should guarantee
      disinfection of ozone-resistant pathogenic microorganisms, including
      Cryptosporidium parvum oocysts, has negligible effects on water matrix components
      but may induce significant transformation of micropollutants. Overall, the
      combination of ozonation at reduced doses and UV treatment leads to an improved
      water quality with regard to disinfection, oxidation of micropollutants and
      minimization of bromate.

PMID- 16635505
TI  - Inhibition of nitrification in laboratory tests and model wastewater treatment
      plants.
AB  - The microbial elimination of nitrogen by combined nitrification and
      denitrification is a well-known technology in wastewater treatment processes.
      Nitrification in wastewater treatment plants is a sensitive microbiological
      process, which can be disturbed by toxic substances. Two laboratory methods for
      nitrification inhibition (ISO standard 9509 and a modification of the respiration
      inhibition test ISO 8192) were investigated with selected substances and compared
      with results from sewage model plants. For the prediction and prevention of
      interferences, the simple but reliable laboratory test methods proved to be very
      suitable. The tests in laboratory plants allowed a much more comprehensive
      evaluation of nitrification processes and showed their dependence on
      biodegradation and adaptation processes. The inhibition of nitrification depended
      on the mode of application and the biodegradability of the potential inhibitory
      compound and was much less severe with biodegradable substances than with poorly
      degradable ones.

PMID- 16635506
TI  - Assessing heavy metal sources in agricultural soils of an European Mediterranean
      area by multivariate analysis.
AB  - According to the European Thematic Strategy for Soil Protection, the
      characterization of the content and source of heavy metals in soils are necessary
      to establish quality standards on a regional level that allow the detection of
      sampling sites affected by pollution. In relation to this, the surface horizons
      of 54 agricultural soils under vegetable crops in the Alicante province (Spain),
      a representative area of the European Mediterranean region, were sampled to
      determine the content of Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Analytical
      determinations were performed by atomic absorption spectroscopy after microwave
      sample digestion in acid solution. Results indicated that heavy metal levels were
      similar to those reported by authors working on agricultural soils from other
      parts of the Mediterranean region, with the exception of Cu and Pb in some
      samples. Multivariate analysis (principal component analysis and cluster
      analysis) was performed to identify a common source for heavy metals. Moreover,
      soil properties were determined in order to characterize agricultural soils and
      to analyze relationships between heavy metal contents and soil properties. The
      content of Co, Cr, Fe, Mn, Ni and Zn were associated with parent rocks and
      corresponded to the first principal component called the lithogenic component. A
      significant correlation was found between lithogenic metals and some soil
      properties such as soil organic matter, clay content, and carbonates, indicating
      an important interaction among them. On the other hand, elements such as Cd, Cu
      and Pb were related to anthropic activities and comprised the second (Cu and Pb)
      and third principal components (Cd), designated the anthropogenic components.
      Generally, Cd, Cu and Pb showed a lower correlation with soil properties due to
      the fact that they remain in available forms in these agricultural soils. Taking
      into account these results and other achieved in other parts of the European
      Mediterranean region, it can be concluded that soil quality standards are highly
      needed to declare soils affected by human induced pollution. This is particularly
      relevant for anthropogenic metals (Cd, Cu and Pb, and in some areas also Zn).
      Further research in other agricultural areas of the region would improve the
      basis for proposing such soil quality standards.

PMID- 16635507
TI  - Recognition and preservation of accessory pudendal arteries during laparoscopic
      radical prostatectomy.
AB  - OBJECTIVES: To determine the incidence of, and ability to preserve, accessory
      pudendal arteries (APAs) in patients undergoing laparoscopic radical
      prostatectomy (LRP). The incidence of APAs is not well established. Preservation
      of APAs may be important for the maintenance of erectile function after
      prostatectomy. Data are limited regarding the ability to preserve APAs during
      laparoscopic surgery. METHODS: At the beginning of each of 70 consecutive
      laparoscopic radical prostatectomies performed at my institution, a purposeful
      search for APAs was performed during dissection of the space of Retzius. The
      operative findings were systematically dictated, and video documentation was
      obtained whenever possible. In every case in which APAs were identified, an
      attempt was made to spare them. RESULTS: Of the 70 patients, 18 (25.7%) were
      identified as having 23 APAs on the left (n = 8), right (n = 5), or both (n = 5)
      sides. Documentation and the technique of preservation are detailed in the
      accompanying video. In all but 1 case, APAs were identified at the initial
      exploration. APAs were preserved in 78.3% of cases. Of 10 preoperatively potent,
      sexually active men undergoing bilateral nerve-sparing surgery, all had
      preservation of APAs. CONCLUSIONS: The incidence of APAs in this consecutive
      series of LRP was 25.7%. Preservation of the APAs was successful in 78.3% of
      those with APAs found. Although occasionally the anatomy may not permit vascular
      preservation, vigilant examination and strategic laparoscopic dissection allow
      APAs to be successfully spared in most cases.

PMID- 16635508
TI  - Laparoscopic partial nephrectomy using the potassium titanyl phosphate laser in a
      porcine model.
AB  - INTRODUCTION: To evaluate the potential and feasibility of the potassium titanyl
      phosphate (KTP) Greenlight laser to perform partial nephrectomy in a porcine
      model. TECHNICAL CONSIDERATIONS: A total of 15 laparoscopic partial nephrectomies
      were performed in 4 Danish land-raised pigs under anesthesia. Transperitoneal
      access was obtained, and using a total of four ports, the 80-W KTP laser was used
      to perform bilateral upper and lower pole partial nephrectomy. The procedures
      were done successfully without renal cooling or clamping of the vessels. The
      estimated blood loss for each procedure was less than 30 mL. Only in one
      operation, in which a secondary renal vein was transected, was any additional
      hemostasis required (a single Endoclip). The mean operating time was 42 minutes
      (range 31 to 59) for each partial nephrectomy. As demonstrated on video, smoke
      formation was, at times, a problem during the procedure, because it reduced
      visibility, making only intermittent application of laser energy possible.
      Histopathologic analysis of the specimens showed a zone of loss of substance
      (less than 1 mm) at the resection line and narrow adjacent zones on both sides of
      the resection line with minimal changes. CONCLUSIONS: We have shown for the first
      time that normally perfused laparoscopic partial nephrectomy using the KTP laser
      is feasible and efficacious in the porcine model. This represents a novel
      application for the KTP laser, which produced excellent renal parenchymal
      hemostatic ablation. We are currently working on ways to improve the visibility
      by reducing smoke formation before undertaking a clinical trial in humans.

PMID- 16635509
TI  - Urodynamic distinctions between idiopathic detrusor overactivity and detrusor
      overactivity secondary to multiple sclerosis.
AB  - OBJECTIVES: To evaluate the urodynamic characteristics of neurogenic detrusor
      overactivity (NDO) secondary to multiple sclerosis (MS) compared with idiopathic
      DO (IDO) to determine whether urodynamic distinctions could differentiate the
      different etiologies of DO. METHODS: The urodynamic characteristics of DO in
      women with MS (n = 54) were compared with the overactive contractions found in
      women with lower urinary tract symptoms and IDO (n = 42). Among other parameters,
      the amplitude of the first overactive contraction, maximal detrusor contraction,
      and threshold volume for the first overactive contraction were evaluated to
      assess the DO severity. A sensitivity analysis using cutoff values determined
      from those urodynamic parameters that differed between the patient groups is
      presented. RESULTS: The amplitude of the first overactive contraction was
      statistically greater in the patients with MS and NDO compared with patients with
      IDO (28.3 cm H2O versus 20.5 cm H2O, P = 0.003), as was the maximal detrusor
      contraction (46.4 cm H2O versus 30.8 cm H2O, P = 0.002). The threshold volume for
      DO was greater among patients with NDO (186.8 mL versus 150.5 mL, P = 0.037),
      likely secondary to the elevated postvoid residual urine volume noted among
      patients with MS (P = 0.049). Using a cutoff value of 30 cm H2O for amplitude of
      the first overactive contraction achieved a positive predictive value of 88% for
      identifying MS in our data set. CONCLUSIONS: The urodynamic characteristics of
      NDO differed significantly from those of IDO. Additional investigation is
      required to determine whether these differences are due to neurogenic influences
      directly on the detrusor muscle through aberrant innervation or by other
      mechanisms, such as enhanced outlet resistance during voiding.

PMID- 16635510
TI  - Continuous positive airway pressure reduces nocturia in patients with obstructive
      sleep apnea.
AB  - OBJECTIVES: To examine whether treatment with continuous positive airway pressure
      (CPAP) reduces nocturia in patients with obstructive sleep apnea (OSA). METHODS:
      This prospective clinical study recruited patients referred to the Rambam Sleep
      Laboratory with suspected OSA. After polysomnography, those found to have no OSA
      were excluded from the study, and the remainder were treated with CPAP. Nocturia
      was assessed at four time points: baseline (average number of awakenings to
      urinate per night during 1 week at home before polysomnography); diagnostic night
      in the laboratory; CPAP titration in the laboratory; and after 1 to 3 months of
      stable CPAP treatment at home (average number of awakenings to urinate per night
      for 1 week). RESULTS: Ninety-seven patients (75 men and 22 women) completed the
      study. The mean +/- SD age was 55 +/- 12 years, body mass index was 33 +/- 7
      kg/m2, and respiratory disturbance index was 34 +/- 24/hr. The mean number of
      awakenings to void at home before CPAP was 2.5 +/- 2.4 times/night; during CPAP,
      it was 0.7 +/- 0.6 time/night (P < 0.001). A total of 73 patients reported
      improvement in nocturia. The mean number of awakenings to void in the laboratory
      was 1.1 +/- 0.9 before CPAP, with a decrease to 0.5 +/- 0.6 during CPAP (P <
      0.001). Weak, but significant, correlations were found in the number of
      awakenings to void before treatment with the respiratory disturbance index (r =
      0.25, P = 0.01) and with minimal oxygen saturation (r = -0.23, P = 0.02).
      CONCLUSIONS: CPAP appears to be an effective treatment for nocturia associated
      with OSA.

PMID- 16635511
TI  - Radical perineal prostatectomy for treatment of localized prostate cancer in
      obese and nonobese patients: a matched control study.
AB  - OBJECTIVES: To compare the perioperative outcomes of severely obese and nonobese
      patients undergoing radical perineal prostatectomy (RPP). METHODS: A cohort of 71
      severely obese patients, as defined by a body mass index of 35 kg/m2 or more, who
      underwent RPP between 1992 and 2003 was retrospectively identified. These
      patients were matched by age, American Society of Anesthesiologists class, and
      year of surgery to a cohort of 71 nonobese patients (body mass index less than 25
      kg/m2). Statistical testing was performed to compare the estimated blood loss,
      transfusion requirements, and complication rates (primary endpoints), as well as
      the length of surgery, intraoperative anesthesia requirements, postoperative
      hematocrit level, length of stay, and surgical margin status (secondary
      endpoints). RESULTS: The mean body mass index +/- standard deviation of patients
      in the obese and nonobese group was 38.9 +/- 4.7 and 22.9 +/- 1.6 kg/m2 (P =
      0.001), respectively. Patients were similar with regard to baseline
      characteristics. Obese and nonobese patients did not demonstrate significant
      differences in mean estimated blood loss (571 +/- 391 and 494 +/- 317 mL,
      respectively; P = 0.06), transfusion rates (2.8% and 7.0%, respectively; P =
      0.45), or positive surgical margin rates (14.1% and 9.9%, respectively; P =
      0.22). The overall complication rates were significantly different at 16.9% and
      7.0% (P = 0.03). CONCLUSIONS: Severely obese patients undergoing RPP had blood
      transfusion rates similar to those of the nonobese patients. Obese RPP patients
      were at increased risk of surgical and anesthesia-related perioperative
      complications, many of which might be avoidable. Specifically, efforts should be
      directed toward preventing the development of lower extremity neurapraxia by
      minimizing the operative time and optimizing patient positioning.

PMID- 16635512
TI  - Role of external beam radiotherapy with low-dose-rate brachytherapy in treatment
      of prostate cancer.
AB  - OBJECTIVES: To report a single-institution experience and analysis of the role of
      supplemental external beam radiotherapy (EBRT) with brachytherapy. EBRT is often
      used in addition to low-dose-rate brachytherapy in the treatment of prostate
      cancer, particularly for disease with adverse features. METHODS: A cohort of 189
      consecutive patients, who had undergone low-dose-rate brachytherapy at our
      institution and who had demographic, disease, and treatment information and a
      minimum of 2 years of follow-up available, constituted the study group. This
      cohort was divided into two major groups according to the use of supplemental
      EBRT. Using two successive prostate-specific antigen rises greater than 1 ng/mL
      as the definition of failure, biochemical failure-free survival curves were
      constructed for the EBRT and no-EBRT groups and compared using the log-rank test.
      Additionally, a multivariate analysis of all major disease and treatment factors
      was performed using the Cox proportional hazards model. RESULTS: Despite the
      greater proportion of adverse disease factors in the EBRT group, the 5-year
      biochemical failure-free survival rate in the EBRT versus no-EBRT groups was 80%
      versus 59%, respectively (P < 0.01). On multivariate analysis, the only factor
      reaching significance in predicting biochemical control was the use of EBRT (P =
      0.043). CONCLUSIONS: In our study, the addition of EBRT conferred a significant
      biochemical control advantage when added to low-dose-rate brachytherapy. Because
      our study was not designed to permit detailed subset analyses, more work is
      needed to determine the precise brachytherapy population that will benefit from
      this use of supplemental EBRT.

PMID- 16635513
TI  - In vitro enhanced cytotoxicity of tumor-infiltrating lymphocytes transfected with
      tumor necrosis factor-related apoptosis-inducing ligand and/or interleukin-2 gene
      in human renal cell carcinoma.
AB  - OBJECTIVES: To investigate whether tumor-infiltrating lymphocytes (TILs)
      transfected with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      and interleukin-2 (IL-2) genes are capable of improving the potency and efficacy
      of propagation and cytotoxicity against renal cell carcinoma (RCC) cells in
      vitro. METHODS: A mammal expression vector system was constructed. TILs were
      transfected by liposome-mediated gene transfection. The degree of cytokine mRNA
      expression was evaluated with Northern blot. Protein expression was determined
      with Western blot and enzyme-linked immunosorbent assay. Cytotoxicity of TILs
      against autologous RCC cells and the human RCC cell line (786-0) were examined by
      chromium release assay. Flow cytometric analyses were performed to determine the
      apoptosis of tumor cells. RESULTS: A high level of expression of the human TRAIL
      and IL-2 stable transfected TILs was observed. The mean IL-2 production was 22.6
      +/- 5.2, 507.7 +/- 52.4, and 549.0 +/- 74.0 ng/10(6) cells/24 hours in the
      TIL/parental, TIL/IL-2, and TIL/TRAIL+IL-2 genes, respectively. The mean
      cytotoxicity (effector/target ratio 20:1) of TIL/parental, TIL/IL-2, TIL/TRAIL,
      and TIL/TRAIL+IL-2 against autologous RCC cells in the percentage of cytolysis
      was 21.2% +/- 4.8%, 32.1% +/- 5.5%, 63.5% +/- 6.6%, and 78.1% +/- 9.63%,
      respectively. These four groups showed cytotoxic activity against allogeneic 786
      0 RCC cells; the corresponding values were 9.8% +/- 3.5%, 12.3% +/- 3.4%, 24.1%
      +/- 4.9%, and 30.4% +/- 6.2%. The number of apoptotic cells was significantly
      greater for autologous RCC cells than for 786-0 cells after TIL/TRAIL and
      TIL/TRAIL+IL-2 treatment. CONCLUSIONS: TIL/TRAIL+IL-2 and TIL/IL-2 were expanded
      by autocrine IL-2. TIL/TRAIL+IL-2 and TIL/TRAIL showed significant cytotoxicity
      that was induced by TRAIL. TILs, including parental TILs and transfected TILs,
      demonstrated a potent cytotoxicity against RCC cells with remarkable selectivity.
      Autologous RCC cells seemed more sensitive than allogeneic RCC cells.

PMID- 16635514
TI  - Use of Stone Cone minimizes stone migration during percutaneous nephrolithotomy.
AB  - We describe a simple and effective method using the Stone Cone to prevent
      migration of stone fragments into the ureter during percutaneous nephrolithotomy.
      This maneuver may reduce the need for antegrade ureteroscopy to remove residual
      fragments, thereby saving time and obviating the need for placement of an
      occlusion balloon.

PMID- 16635515
TI  - Colonic perforation during percutaneous nephrolithotomy: study of risk factors.
AB  - OBJECTIVES: To identify the risk factors implicated in colonic perforation during
      percutaneous nephrolithotomy. METHODS: From 1985 to 2004, 5039 percutaneous
      nephrolithotomy procedures were performed in our center. Colonic perforation
      complicated 15 procedures (0.3%). The patient files were retrospectively reviewed
      for detection of preoperative risk factors as shown by multivariate statistical
      analysis. The operative details and postoperative course were also studied to
      determine the time and mode of diagnosis of colonic injury and treatment
      strategies and outcome. RESULTS: All injuries were retroperitoneal. The mean
      patient age was 57 +/- 8.4 years. Of the 15 patients, 11 were men and 4 were
      women. The left side was affected in 10 patients (66.6%). The right side was
      injured only in those with horseshoe kidneys or with recurrent disease. Colonic
      perforation complicated lower caliceal puncture in 12 procedures (80%) and
      complicated upper caliceal punctures in those with horseshoe kidneys or chronic
      colonic distension. Significant independent risk factors were advanced patient
      age and the presence of a horseshoe kidney. The diagnosis was established
      intraoperatively in 5 patients and postoperatively in 10, 5 of whom presented
      with colocutaneous fistula. The diagnosis was confirmed with abdominal computed
      tomography or opacification of the colon during antegrade or retrograde
      pyelography. Conservative treatment was successful in all but 2 patients who
      required colostomy. CONCLUSIONS: Significant independent risk factors for colonic
      perforation during percutaneous nephrolithotomy were advanced patient age and the
      presence of a horseshoe kidney. Early diagnosis and proper treatment represent
      the key to minimizing patient morbidity and avoiding serious complications.

PMID- 16635516
TI  - Laparoscopic pyeloplasty: evolution of a new gold standard.
AB  - OBJECTIVES: To report our series of laparoscopic dismembered pyeloplasty for the
      treatment of primary and secondary ureteropelvic junction obstruction and to
      review the current status of this procedure. METHODS: A total of 170 consecutive
      cases of laparoscopic pyeloplasty (156 for primary and 14 for secondary
      ureteropelvic junction obstruction) were performed or supervised by a single
      surgeon (C.G.E). A four-port extraperitoneal approach was used in all but 3
      cases, which were performed transperitoneally. RESULTS: The median operative time
      was 140 minutes. The complication rate was 7.1%, and the conversion rate was
      0.6%, with no conversion in the last 161 cases. The median postoperative hospital
      stay was 3 nights. Crossing vessels were encountered in 42% of cases, and in 11
      patients, coexisting renal calculi were successfully removed. At a median follow
      up of 12 months, the success rate was 96.2%. CONCLUSIONS: Laparoscopic
      dismembered pyeloplasty produces functional results comparable to that of open
      surgery with the advantages of a minimally invasive procedure. Our results are
      consistent with previous series and support the view that laparoscopic
      pyeloplasty is moving rapidly toward replacing open surgery as the gold standard
      in the treatment of ureteropelvic junction obstruction.

PMID- 16635517
TI  - Prevalence of benign microscopic hematuria among women with interstitial
      cystitis: implications for evaluation of genitourinary malignancy.
AB  - OBJECTIVES: To assess the prevalence of benign microscopic hematuria among a
      cohort of women with clinical interstitial cystitis (IC). METHODS: A total of 100
      women were prospectively assessed for microscopic hematuria with postvoid sterile
      catheterization. The evaluation for all patients included urine culture,
      potassium sensitivity test (PST), cystoscopy with hydrodistension under general
      anesthesia, and symptom assessment with the Pelvic Pain and Urgency/Frequency
      (PUF) questionnaire. RESULTS: The mean age +/- SD was 37 +/- 15 years, with no
      difference noted in those with or without microscopic hematuria (P = 0.71).
      Microscopic hematuria was present in 24 (24%) of the 100 women. No patient had
      gross hematuria, positive urine culture, or cystoscopic findings suspicious for
      malignancy. The mean PUF score was 17 +/- 6. The PST was positive in 92 (92%) of
      100 women, and 8 patients had only cystoscopic findings diagnostic of IC. The
      likelihood of a positive PST or positive cystoscopic findings among patients with
      microscopic hematuria was similar to that of patients without microscopic
      hematuria. The PST results correlated with the cystoscopic findings (P < 0.001).
      Of 36 patients with positive cystoscopic findings, 28 (78%) had a positive PST,
      and 28 (30%) of 92 with a positive PST had positive cystoscopy findings.
      CONCLUSIONS: In this cohort of women with IC, the prevalence of benign
      microscopic hematuria was 24%. These data suggest that in women at low risk of
      genitourinary malignancy who have clinical IC, microscopic hematuria may be an
      incidental finding.

PMID- 16635518
TI  - Localized amyloidosis of the urinary tract: case series of nine patients.
AB  - OBJECTIVES: To report 9 cases of primary localized amyloidosis of the urinary
      tract and correlate the pathologic findings with clinical and cystoscopic
      information. METHODS: Patients diagnosed with amyloidosis of the ureters, urinary
      bladder, or urethra from 1976 to 2003 were identified. Their medical records were
      reviewed, and histochemical and immunoperoxidase stains were performed on the
      tissue. RESULTS: Eight cases of amyloidosis of the urinary bladder and one of the
      renal pelvis/ureter were identified. None of our cases showed evidence of
      systemic amyloidosis. Of the 8 patients with amyloidosis of the urinary bladder,
      5 presented with gross hematuria and 1 with irritative bladder symptoms and 2 had
      amyloidosis detected during cystoscopic follow-up for urothelial carcinoma. The
      patient with amyloidosis of the renal pelvis/ureter presented with flank pain and
      gross hematuria. The clinical impression was malignancy in 75% of the bladder
      cases. Most patients with bladder involvement were treated with localized bladder
      resection; however, 1 patient required total cystectomy for symptom control. Of 5
      patients with follow-up information, 2 developed recurrence. The pathologic
      assessment diagnosed amyloid deposits consistent with primary or AL type amyloid
      in all cases. Immunoperoxidase stains revealed lymphoid cells in the vicinity of
      the amyloid deposits to be lambda-restricted in 78% of cases. CONCLUSIONS:
      Primary amyloidosis of the urinary tract is a rare condition that mimics
      malignancy in its clinical presentation and cystoscopic appearance and on
      diagnostic imaging. In our study, all cases of urinary amyloid deposits
      represented localized amyloidosis rather than manifestations of systemic
      amyloidosis. Monoclonal lymphoid populations evolving from chronic inflammation
      in the urinary tract may be the source of the amyloid AL proteins.

PMID- 16635519
TI  - Expression and antigenicity of survivin, an inhibitor of apoptosis family member,
      in bladder cancer: implications for specific immunotherapy.
AB  - OBJECTIVES: To assess the expression of survivin in transitional cell carcinoma
      of the bladder and to study whether survivin is a transitional cell carcinoma
      specific antigen that could be a target for immunotherapy. Survivin, an inhibitor
      of apoptosis family member, has been reported to be expressed in various cancers
      but not in normal adult tissues. METHODS: Immunohistochemical staining for
      survivin and human leukocyte antigen (HLA) class I was performed on specimens
      from 88 patients who underwent transurethral resection and radical cystectomy. To
      determine whether survivin was recognized as a tumor antigen by the host immune
      system, we assessed anti-survivin antibodies in the sera of 52 patients and 18
      healthy volunteers with an enzyme-linked immunosorbent assay using recombinant
      survivin. RESULTS: Survivin and HLA class I were expressed in 77 (87.5%) and 59
      (67.0%) of the 88 bladder cancer specimens, respectively, and 56 (63.6%)
      expressed both survivin and HLA class I. The absorbance values of anti-survivin
      antibodies in patients with bladder cancer were significantly greater than those
      in the healthy volunteers. A relationship was found between the level of serum
      anti-survivin antibodies and the staining intensity of survivin in the specimen.
      CONCLUSIONS: Survivin is expressed in carcinoma of the bladder with high
      sensitivity. It is suggested that survivin is presented on HLA class I molecules
      of antigen-presenting cells in 64% of patients with bladder cancer. Therapeutic
      targeting of survivin in bladder cancer is a future possibility.

PMID- 16635520
TI  - Accurate prediction of need for invasive treatment in alpha1-blocker treated
      patients with benign prostatic hyperplasia not possible: bootstrap validation
      analysis.
AB  - OBJECTIVES: Frequently, statistically significant prognostic factors are reported
      in published studies with suggestions that disease management should be modified.
      However, the clinical relevance of such factors is rarely quantified. We
      evaluated the accuracy of predicting the need for invasive treatment among
      patients with benign prostatic hyperplasia treated conservatively with alpha1
      blockers. METHODS: Information on eight prognostic factors was collected from 280
      patients treated with alpha1-blockers. Using the proportional hazards regression
      coefficients, a risk score for retreatment was calculated for each patient. The
      analyses were repeated on 1000 groups of 280 patients sampled from the original
      case series. The results from these "bootstrap analyses" were compared with the
      original results. RESULTS: Three statistically significant predictors of
      retreatment were identified. The 20% of patients with the greatest risk score had
      an 18-month risk of retreatment of only 20% (this should ideally approach 100%).
      Analyses of less than one half of all the bootstrap samples resulted in the same
      three significant prognostic factors. The 20% of patients with the greatest risk
      score in each of the 1000 samples experienced a highly variable risk of
      retreatment of 0% to 42%. CONCLUSIONS: Strongly significant predictors for
      retreatment suggest the need for a change in disease management, but 4 of the 5
      high-risk patients would be overtreated with a modified policy. The
      subclassification of patients with a relatively low risk and high risk of
      retreatment appeared far from accurate. Internal validation procedures may warn
      against the invalid translation of statistical significance into clinical
      relevance.

PMID- 16635521
TI  - Prospective study of safety margins in partial nephrectomy: intraoperative
      assessment and contribution of frozen section analysis.
AB  - OBJECTIVES: To evaluate prospectively a healthy parenchymal safety margin during
      conservative surgery for renal cell carcinoma. METHODS: From 1997 to 2001,
      elective nephron-sparing surgery was performed through a flank incision in 61
      consecutive patients (mean age 59.4 years, range 34.2 to 78.5). The mean tumor
      size was 32 mm (range 12 to 50). The tumor localization was juxtahilar in 10 and
      distant in 51. Prospective margin assessment used the following protocol. Margins
      were evaluated macroscopically by the surgeon, controlled by frozen section
      analysis, and subsequently measured during histologic examination. All patients
      were monitored with computed tomography scans, with a mean follow-up of 72.5
      months (range 46 to 95). RESULTS: The histologic type was clear cell in 42
      patients, papillary in 17, and chromophobic cell in 2. Of the 61 patients, 57 had
      1997 TNM Stage pT1 and 4 had Stage pT2. The Furhman grade was grade 1 in 16,
      grade 2 in 35, and grade 3 in 10. No tumor margin was positive. Frozen section
      analysis and routine histologic examination yielded 53 complete and 8 incomplete
      margins compared with 51 and 10, respectively, as assessed by the surgeons. The
      mean peritumoral margin was 7 mm (range 4 to 10) for the cortex and 2 mm (range 0
      to 5) for the deep part. No patient developed locoregional or metastatic relapse.
      CONCLUSIONS: No apparent relationship was observed between peritumoral margin
      width and the risk of disease progression, even for tumors abutting the hilum,
      rendering illusory a safety margin greater than 1 cm. Although the surgeons'
      macroscopic margin evaluations were accurate, frozen section analysis is
      mandatory when the margin status is in doubt. In all cases, margin negativity
      remains an oncologic imperative.

PMID- 16635522
TI  - Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human
      clitoris: immunohistochemical and molecular biology study.
AB  - OBJECTIVES: Only a little research has focused on the evaluation of female sexual
      function. With sexual stimulation, the clitoris becomes engorged with blood and
      tumescent. Nevertheless, only little is known about the significance of the
      cyclic nucleotide-mediated signal transduction in the control of this process. We
      sought to elucidate the presence of the phosphodiesterase (PDE) isoenzymes 3, 4,
      and 5 in the human clitoris using immunohistochemical and molecular biology
      methods. METHODS: Thin sections of clitoral specimens were incubated with primary
      antibodies directed against PDE isoenzymes 3, 4, and 5. Next, the sections were
      incubated with either Texas red or fluorescein isothiocyanate-labeled secondary
      antibodies, and visualization was done using laser microscopy. The expression of
      mRNA encoding for various PDE isoenzymes was evaluated using reverse
      transcriptase polymerase chain reaction. RESULTS: Immunofluorescence indicating
      the presence of PDE4 (cyclic adenosine monophosphate-PDE) was observed in the
      nonvascular smooth musculature of the corpus cavernosum clitoris, sinusoidal
      endothelial and subendothelial layers, and nerve fibers innervating the tissue.
      Immunoreactivity specific for PDE5 (cyclic guanosine monophosphate-PDE) was
      limited to the smooth muscle of the clitoral erectile tissue. The fluorescein
      isothiocyanate reaction indicating the expression of PDE3 (cyclic adenosine
      monophosphate-PDE) was registered to a certain degree only in the clitoral
      epidermis. In the reverse transcriptase polymerase chain reaction studies, a
      predominant expression of mRNA encoding for PDE1A was registered, but only small
      amounts of mRNA encoding for PDE4 and PDE5 were detected. CONCLUSIONS: Our
      results have demonstrated the presence of cyclic adenosine monophosphate-PDE and
      cyclic guanosine monophosphate-PDE in the human clitoris and may indicate a
      regulatory function of these enzymes in the cyclic nucleotide-mediated control of
      smooth muscle tone.

PMID- 16635524
TI  - Buccal mucosa graft urethroplasty for recurrent stricture of female urethra.
AB  - Recurrent stricture of the female urethra is an uncommon, yet difficult,
      condition to manage. This report demonstrates a ventral buccal mucosa onlay graft
      technique as a feasible and reliable method of repairing this condition.

PMID- 16635523
TI  - Cultured smooth muscle cells of the human vesical sphincter are more sensitive to
      histamine than are detrusor smooth muscle cells.
AB  - OBJECTIVES: To compare histamine receptor expression in cultured smooth muscle
      cells from the human detrusor and internal sphincter using receptor-specific
      agonists. METHODS: Smooth muscle cells from the bladder dome and internal
      sphincter were cultured from 5 male patients undergoing cystectomy for bladder
      cancer therapy. Calcium transients in cells stimulated with carbachol, histamine,
      histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R),
      and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine
      receptor proteins were detected by Western blot analysis and immunocytochemistry.
      RESULTS: H1R, H2R, and H3R expression was found in tissue and cultured cells.
      Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%,
      respectively). Histamine stimulated significantly more cells than carbachol in
      detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in
      detrusor and sphincter cells were comparable and did not differ from those to
      histamine in detrusor cells. However, histamine and specific agonists stimulated
      more sphincter cells than did carbachol (P <0.001), and the calcium increase was
      greater in sphincter cells than in detrusor cells. Single cell analysis revealed
      comparable H2R responses in detrusor and sphincter cells, but H1R and H3R
      mediated calcium reactions were significantly greater in sphincter cells.
      CONCLUSIONS: Histamine very effectively induces calcium release in smooth muscle
      cells. In sphincter cells, histamine is even more effective than carbachol
      regarding the number of reacting cells and the intracellular calcium increase.
      Some of the variability in the outcome of antihistaminic interstitial cystitis
      therapies might be caused by the ineffectiveness of the chosen antihistaminic or
      unintentional weakening of sphincteric function.

PMID- 16635525
TI  - The psychosocial inventory of ego strengths: examination of theory and
      psychometric properties.
AB  - The psychosocial inventory of ego strengths (PIES) was devised as a measure of
      Erikson's eight ego strengths. The present investigation extended previous
      research through examination of the validity and reliability of the PIES among
      502 high school students. The study also included an appraisal of Erikson's ego
      strengths as indices of psychosocial well-being. Reliability of the subscales of
      the PIES was shown through acceptable Cronbach's alphas. As expected, higher
      scores on ego strengths were positively correlated with psychosocial indictors of
      identity achievement, self-esteem, locus of control, empathic concern,
      perspective-taking, and positive forms of coping. Lower scores on ego strengths
      were related to less desirable psychosocial constructs. Biological sex and age
      differences also are reported. Based on the findings, the study offers validation
      of psychosocial theory. As well, the PIES is recommended for use among high
      school students.

PMID- 16635526
TI  - Antimicrobial activities of silver used as a polymerization catalyst for a wound
      healing matrix.
AB  - Wound healing is a complex and orchestrated process that re-establishes the
      barrier and other functions of the skin. While wound healing proceeds apace in
      healthy individual, bacterial overgrowth and infection disrupts this process with
      significant morbidity and mortality. As such, any artificial matrix to promote
      wound healing must also control infecting microbes. We had earlier developed a
      two-part space-conforming gel backbone based on polyethyleneglycol (PEG) or
      lactose, which used ionic silver as the catalyst for gelation. As silver is
      widely used as an in vitro antimicrobial, use of silver as a catalyst for
      gelation provided the opportunity to assess its function as an anti-microbial
      agent in the gels. We found that these gels show bacteriostatic and bactericidal
      activity for a range of Gram-negative and Gram-positive organisms, including
      aerobic as well as anaerobic bacteria. This activity lasted for days, as silver
      leached out of the formed gels over a day in the manner of second-order decay.
      Importantly the gels did not limit either cell growth or viability, though cell
      migration was affected. Adding collagen I fragments to the gels corrected this
      effect on cell migration. We also found that the PEG gel did not interfere with
      hemostasis. These observations provide the basis for use of the gel backbones for
      incorporation of anesthetic agents and factors that promote wound repair. In
      conclusion, silver ions can serve dual functions of catalyzing gelation and
      providing anti-microbial properties to a biocompatible polymer.

PMID- 16635527
TI  - The placenta in pre-eclampsia and intrauterine growth restriction: studies on
      exchange surface areas, diffusion distances and villous membrane diffusive
      conductances.
AB  - We test the null hypothesis that the morphometric diffusive conductance of the
      placental villous membrane does not alter in pregnancies complicated by
      intrauterine growth restriction (IUGR) or pre-eclampsia (PE). Placentas were
      collected from cases of normotensive IUGR, pure PE, PE+IUGR and from control
      pregnancies. Microscopical fields on formalin-fixed, trichrome-stained
      histological sections were randomly sampled for location and orientation. Using
      stereological methods, the exchange surface areas of peripheral (terminal and
      intermediate) villi and their fetal capillaries and the arithmetic and harmonic
      mean thicknesses of the villous membrane (maternal aspect of trophoblast to
      luminal aspect of vascular endothelium) were estimated. An index of the
      variability in thickness of this membrane, and an estimate of its oxygen
      diffusive conductance, was derived secondarily. Group comparisons were drawn
      using two-way analysis of variance to identify main effects (of PE or IUGR) and
      interaction effects (between PE and IUGR). PE did not have significant effects on
      placental morphology and there were no significant effects of PE or IUGR on
      membrane thickness or its variability. In contrast, IUGR (with or without PE) was
      associated with reduced surface areas and this was the principal factor leading
      to a smaller membrane diffusive conductance in these placentas. When account was
      taken of fetal mass, specific conductance showed no effects of PE or IUGR despite
      the mass-specific conductance in pure IUGR placentas appearing to be smaller than
      that in controls. The decline in total conductances is indicative of
      perturbations operating at the levels of villous trophoblast and fetal
      vasculature and these may contribute to fetal hypoxic stress.

PMID- 16635528
TI  - The distinct temperament profiles of bipolar I, bipolar II and unipolar patients.
AB  - BACKGROUND: Despite a plethora of studies, controversies abound on whether the
      long-term traits of unipolar and bipolar patients could be differentiated by
      temperament and whether these traits, in turn, could be distinguished from
      subthreshold affective symptomatology. METHODS: 98 bipolar I (BP-I), 64 bipolar
      II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when
      recovered from discrete affective episodes) and 617 relatives, spouses or
      acquaintances without lifetime RDC diagnoses (the comparison group, CG) were
      administered a battery of 17 self-rated personality scales chosen for theoretical
      relevance to mood disorders. Subsamples of each of the four groups also received
      the General Behavior Inventory (GBI). RESULTS: Of the 436 personality items, 103
      that significantly distinguished the three patient groups were subjected to
      principal components analysis, yielding four factors which reflect the
      temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity
      Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in
      emotional stability and extroversion; BP-II emerged as labile in mood, energetic
      and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and
      brooding. Gender and age did not have marked influence on these overall profiles.
      Within the MDD group, those with baseline dysthymia were the most pathological
      (i.e., high in neuroticism, insecurity and introversion). Selected GBI items
      measuring hypomania and biphasic mood changes were endorsed significantly more
      often by BP-II. Finally, it is relevant to highlight a methodologic finding about
      the precision these derived temperament factors brought to the UP-BP
      differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP
      scored high on this measure: yet, in the case of BP-II high neuroticism was
      largely due to mood lability, in UP it reflected subdepressive traits.
      LIMITATION: We used self-rated personality measures, a possible limitation
      generic to the paper-and-pencil personality literature. It is therefore likely
      that BP-I may have over-rated their "sanguinity"; or should one consider such
      self-report as a reliable reflection of one's temperament? One can raise similar
      unanswerable questions about "depressiveness" and "mood lability." CONCLUSION: As
      contrasted to CG and published norms, the postmorbid self-described "usual"
      personality is 1) sanguine among many, but not all, BP-I; 2) labile or
      cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is
      further noteworthy that with the exception of BP-II, the temperament scores of BP
      I and MDD were within one SD from published norms. Rather than being
      pathological, these attributes are best conceived as subclinical temperamental
      variants of the normal, thereby supporting the notion of continuity between
      interepisodic and episodic phases of affective disorders. These findings overall
      are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis
      II constructs as being pathological and sharply demarcated from affective
      episodes.

PMID- 16635529
TI  - Comparison between hyperventilation and breath-holding in panic disorder:
      patients responsive and non-responsive to both tests.
AB  - Our aim was to compare the demographic and psychopathological features of panic
      disorder (PD) patients who underwent hyperventilation and breath-holding
      challenge tests, and to describe the features of patients who had a panic attack
      after both tests versus those patients who did not experience panic after either
      test. Eighty-five PD patients were induced to hyperventilate (30 breaths/min) for
      4 min, and a week later to hold their breath for as long as possible four times
      with a 2-min interval in between. Anxiety scales were applied before and after
      the tests. Patients who responded with a panic attack to both tests (BPA, n = 25)
      were compared with patients who experienced spontaneous panic attacks but did not
      panic in response to the two tests (NPA, n = 16). The BPA group had a
      significantly higher presence of respiratory symptoms during a panic attack. The
      criteria for the respiratory PD subtype were fulfilled in 18 (72.0%) BPA patients
      and in 6 (37.5%) NPA patients. The BPA patients had a later onset of panic
      disorder and a higher familial prevalence of PD. Our data suggest that there is a
      distinction between PD patients who were sensitive to both hyperventilation and
      breath-holding tests and PD patients who were not affected by the challenge
      tests. The panic attack may be a final common pathway for different types of
      stimuli, and respiratory tests may characterize different PD subgroups.

PMID- 16635530
TI  - The BEEP Stavanger Workshop: Mesocosm exposures.
AB  - Within the BEEP project (Biological Effects of Environmental Pollution in Marine
      Ecosystems) the Work Package 1 was addressed to the development of new and more
      sensitive biomarkers of exposure in several sentinel organisms. Within this
      framework, common mesocosm exposures of organic pollutants relevant for marine
      ecosystems were conducted in the facilities of Akvamiljo a/s (Stavanger, Norway).
      In the first experiment, Atlantic cod (Gadus morhua), turbot (Scophthalmus
      maximus) and shore crab (Carcinus maenas) were exposed to nonylphenol, North Sea
      crude oil and a combination of crude oil and alkylated phenols. Mussels (Mytilus
      edulis) were exposed to North Sea crude oil and a combination of crude oil,
      alkylated phenols and PAHs. In the second experiment, Atlantic cod, turbot,
      mussel and spider crab (Hyas araneus) were exposed to the plasticizers bisphenol
      A and diallyl phatalate and the brominated flame retardant BDE-47. The main
      purpose of the present study was to provide the 30 participating Institutes with
      samples which had been exposed to defined contaminant concentrations in a
      controlled laboratory exposure for 3 weeks. This paper describes the mesocosm
      experimental design, the transplantation and treatment of the organisms, and the
      contaminant exposures.

PMID- 16635531
TI  - Biomarkers in mussels from a copper site gradient (Visnes, Norway): an integrated
      biochemical, histochemical and histological study.
AB  - In the present work, mussels (Mytilus edulis) were transplanted into a copper
      (Cu) gradient in Visnes (Norway) for a period of 3 weeks during November 2003.
      Sites 1 and 2 showed similar low levels of Cu, site 3 had intermediate Cu levels
      and site 4 was the most polluted with Cu as confirmed by AAS of digestive gland
      tissue. Values of lysosomal membrane labilization period were significantly lower
      at sites 3 and 4 compared to sites 1 and 2. The volume density and size of
      lysosomes was significantly decreased at site 4. The volume density of neutral
      lipids was also significantly lower at site 4 compared with the rest of sites.
      The volume density of lipofuscins showed significantly higher values at sites 2
      and 3 compared to the reference site 1. Similar results were obtained regarding
      bioavailable metal levels measured by autometallography. All together, results
      are indicative of exocytosis of metal-containing lysosomes and lipofuscins to the
      digestive tubule lumen in mussels from site 4. In fact, autometallographic metal
      deposits were detected in digestive tubule lumen, brown cells and stomach in site
      4 mussels. In agreement, there was a loss of digestive cells in mussels from site
      4 (atrophy of the digestive epithelium) and cell type replacement (diminished
      volume density of digestive cells and increased volume density of basophilic
      cells). In conclusion, selected biomarkers indicated that mussels transplanted to
      sites closest to the Cu mine showed significant differences in metal accumulation
      pattern and in organization of the digestive gland tissue. Finally, female
      mussels closest to the Cu mine showed advanced gametogenesis with higher gonad
      index and vitellogenin-like protein levels than mussels at sites 1 and 2.

PMID- 16635532
TI  - Recurrent intracardiac thrombosis as an unusual manifestation of inherited
      thrombophilia.
AB  - Patients with inherited thrombophilia are at high risk for the development of
      venous thrombosis that manifests mainly as deep venous thrombosis of the legs
      and/or pulmonary embolism. We report spontaneous right-sided intracardiac
      thrombosis in a young man as an unusual manifestation of inherited thrombophilia.
      The diagnosis of thrombophilia was confirmed by demonstration of the prothrombin
      G20210A-mutation in the homozygous state. A second spontaneous intracardiac
      thrombosis occurred 3 years after discontinuation of oral anticoagulant
      treatment. This indicates the high risk for recurrence in patients developing
      intracardiac thrombosis in the absence of an underlying cardiac disease and
      warrants long-term oral anticoagulant treatment.

PMID- 16635533
TI  - Molecular techniques in wastewater: Understanding microbial communities,
      detecting pathogens, and real-time process control.
AB  - Traditionally, the detection of pathogens in water, wastewater, and other
      environmental samples is restricted by the ability to culture such organisms from
      complex environmental samples. During the last decade the use of molecular
      methods have supplied the means for examining microbial diversity and detecting
      specific organisms without the need for cultivation. The application of molecular
      techniques to the study of natural and engineered environmental systems has
      increased our insight into the vast diversity and interaction of microorganisms
      present in complex environments. In this paper, we will review the current and
      emerging molecular approaches for characterizing microbial community composition
      and structure in wastewater processes. Recent studies show that advances in
      microarray assays are increasing our capability of detecting hundreds and even
      thousands of DNA sequences simultaneously and rapidly. With the current progress
      in microfluidics and optoelectronics, the ability to automate a
      detection/identification system is now being realized. The status of such a
      system for wastewater monitoring is discussed.

PMID- 16635534
TI  - Feasibility and safety of G-CSF administration to induce bone marrow-derived
      cells mobilization in patients with end stage liver disease.
AB  - BACKGROUND/AIMS: To evaluate feasibility, safety and pattern of bone marrow
      derived cells (BMC) mobilization in patients with end stage liver cirrhosis
      following granulocyte-colony stimulating factor (G-CSF) administration. METHODS:
      Eight patients with severe liver cirrhosis (Child-Pugh score B-C, spleen diameter
      less than 170 mm) were included. They were treated with G-CSF (5 microg/kg b.i.d
      for three consecutive days) to mobilize BMC, evaluated as circulating CD34+ve
      cells (flow cytometry) and myeloid CFU-GM progenitors (in vitro colony growth
      assay). Co-expression in CD34+ve cells markers of differentiation (Thy1, CD133,
      CXCR4, c1qRp) were investigated on CD34+ve cells by double direct
      immunofluorescence. Data from 40 healthy haematopoietic stem cell donors were
      used as controls. RESULTS: Mobilization of CD34+ve cells occurred in all
      patients. It was paralleled by expansion of circulating CFU-GM progenitors.
      Circulating CD34+ve cells co-expressed epithelial and stem cell markers in both
      cirrhotics and volunteer stem cell donors. G-CSF was well tolerated, no adverse
      event occurred, a significant reversible increase of splenic longitudinal
      diameter was observed. CONCLUSIONS: (i) G-CSF mobilization of BMC co-expressing
      epithelial and stem markers occurred in all cirrhotic patients; (ii) splenomegaly
      up to 170 mm does not prevent safe BMC mobilization following G-CSF in patients
      with end stage liver disease; (iii) mobilized BMC may represent an easy immature
      cell source potentially useful for novel approaches for liver regeneration.

PMID- 16635535
TI  - Upregulation of TNF-alpha production signaling pathways in monocytes from
      patients with advanced cirrhosis: possible role of Akt and IRAK-M.
AB  - BACKGROUND/AIMS: In cirrhosis, tumor necrosis factor (TNF)-alpha overproduction
      is involved in both the systemic complications and progression of liver injury.
      Since monocytes from patients with advanced cirrhosis have an increase in
      lipopolysaccharide (LPS)-induced TNF-alpha production, we hypothesized that an
      upregulation of TNF-alpha production pathways and/or alteration of constitutive
      and inducible suppressor of TNF-alpha hyperproduction (protein kinase B (Akt) and
      interleukin-1 receptor-associated kinase (IRAK)-M, respectively) should be found
      in monocytes of these patients. Thus, we investigated ex vivo the signaling
      pathways of TNF-alpha production before and after LPS incubation in monocytes
      from noninfected Child-Pugh C patients with advanced cirrhosis and healthy
      subjects. METHODS: TNF-alpha production, expressions of intracellular TNF-alpha,
      toll-like receptor-4 (TLR4), IkappaB-alpha, IRAK-1, IRAK-M, mitogen-activated
      protein (MAP) kinases and Akt activity were measured in monocytes. RESULTS:
      Cirrhotic monocytes without LPS have less TLR4 expression, less IkappaB-alpha
      protein levels, more TNF-alpha expression, higher MAP kinase activities and
      decreased Akt activity than control monocytes. In cirrhotic monocytes, LPS
      induced TNF-alpha hyperproduction and signaling upregulation were associated with
      a lack of IRAK-M induction. CONCLUSIONS: Upregulated signaling pathways of the
      TNF-alpha production, decreased Akt activity and a lack of IRAK-M induction may
      be involved in the process of cirrhotic monocyte sensitization to produce TNF
      alpha.

PMID- 16635536
TI  - A prospective study of isolated human hepatocyte function following liver
      resection for colorectal liver metastases: the effects of prior exposure to
      chemotherapy.
AB  - BACKGROUND/AIMS: Chemotherapy is increasingly used prior to resection of
      colorectal liver metastases, yet few studies have addressed its effect on the
      viability and function of hepatocytes. This study evaluated the effect of pre
      operative chemotherapy on human hepatocytes. METHODS: Studies were carried out on
      isolated hepatocytes from 47 patients undergoing hepatectomy for colorectal
      metastases. The function of drug metabolising enzymes in hepatocytes was assessed
      in vitro, as well as hepatocyte integrity and culture longevity. These results
      were compared between patients undergoing no pre-operative chemotherapy (N = 8),
      5 fluorouracil (5FU) post-bowel resection (N = 20), and neo-adjuvant 5FU alone (N
      = 7) or in a combination with oxaliplatin (N = 12). RESULTS: Average cell
      viability at isolation determined by trypan blue dye exclusion was 71% with no
      significant difference between the no chemotherapy or pre-resection chemotherapy
      groups. There was no significant difference in LDH leakage and cellular ATP
      content over a 96-h time course between the patient treatment groups. The
      function of cytochromes P450 (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP3A4) and
      phase II enzymes (UDP-glucuronosyltransferase and sulphotransferase) was not
      adversely affected by pre-operative chemotherapy. CONCLUSIONS: Pre-resection
      chemotherapy does not impair the function or culture integrity of hepatocytes
      isolated at the time of liver resection.

PMID- 16635537
TI  - Peptide ligands targeting integrin alpha3beta1 in non-small cell lung cancer.
AB  - Lung cancer is one of the most common cancers and is the leading cause of cancer
      death. We wish to identify peptide ligands for unique cell surface receptors of
      non-small lung cancer with the hope of developing these ligands as diagnostic and
      therapeutic agents. Using the method of 'one-bead one-peptide' combinatorial
      chemistry, a library of random cyclic octapeptides was synthesized on polystyrene
      beads. This library was used to screen for peptides that promoted attachment of
      lung adenocarcinoma cells employing a 'cell-growth-on-bead' assay. Consensus
      peptide sequences of cNGXGXXc were identified. These peptides promoted cell
      adhesion by targeting integrin alpha3beta1 over-expressed in non-small lung
      cancer cells. These peptide beads can be applied to capture cancer cells in
      malignant pleural fluid for purpose of diagnosis of lung cancer.

PMID- 16635538
TI  - Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA
      vaccine of Leishmania donovani.
AB  - The nucleoside hydrolase (NH36) of Leishmania (L.) donovani is a vital enzyme
      which releases purines or pyrimidines of foreign DNA to be used in the synthesis
      of parasite DNA. As a bivalent DNA vaccine, the VR1012-NH36 was immunoprotective
      against visceral and cutaneous murine leishmaniasis. In this work we tested the
      immunotherapy against Leishmania (L.) chagasi infection, using two doses of 100
      or 20 microg VR1012-NH36 vaccine (i.m. route), and, as a possible
      immunomodulator, aqueous garlic extract (8 mg/kg/day by the i.p. route), which
      was effective in immunotherapy of cutaneous murine leishmaniasis. Liver parasitic
      load was significantly reduced following treatment with 100 microg (91%) and 20
      microg (77%) of the DNA vaccine, and by 20 microg DNA vaccine and garlic extract
      (76%) (p=0.023). Survival was 33% for saline controls, 100% for the 100 microg
      vaccine, and 83 and 67% for the 20 microg vaccine with and without garlic extract
      addition, respectively. Garlic treatment alone did not reduce parasite load
      (p>0.05), but increased survival (100%). The NH36-DNA vaccine was highly
      effective as a new tool for the therapy and control of visceral leishmaniasis,
      while the mild protective effect of garlic might be related to an unspecific
      enhancement of IFN-gamma secretion.

PMID- 16635539
TI  - Heavy metal pollution disturbs immune response in wild ant populations.
AB  - Concern about the effects of environmental contaminants on immune function in
      both humans and wildlife is growing and practically nothing is known about this
      impact on terrestrial invertebrates, even though they are known to easily
      accumulate pollutants. We studied the effect of industrial heavy metal
      contamination on immune defense of a free-living wood ant (Formica aquilonia). To
      find out whether ants show an adapted immune function in a polluted environment,
      we compared encapsulation responses between local and translocated colonies.
      Local colonies showed higher heavy metal levels than the translocated ones but
      the encapsulation response was similar between the two groups, indicating that
      the immune system of local ants has not adapted to high contamination level. The
      encapsulation response was elevated in moderate whereas suppressed in high heavy
      metal levels suggesting higher risk for infections in heavily polluted areas.

PMID- 16635540
TI  - Disability pension among immigrants in Sweden.
AB  - Using large samples, disability pensions among foreign-born and native-born women
      and men living in Sweden is studied here for the period 1981-1999. The results
      show foreign-born individuals having higher rates of disability pension. The risk
      of being on disability pension is very low for newly arrived immigrants, but
      increases rapidly on a yearly basis after immigration. Higher rates of disability
      pension are reported for persons born in Greece, Yugoslavia, Turkey and Finland.
      Results from multivariate analysis indicate that factors such as education,
      country of residence and marital status cannot fully explain the high rates of
      disability pension observed among many immigrant groups. Future research needs to
      address which possible causes are most important for policies to address.

PMID- 16635541
TI  - Adverse selection in a voluntary Rural Mutual Health Care health insurance scheme
      in China.
AB  - This study examines adverse selection in a subsidized voluntary health insurance
      scheme, the Rural Mutual Health Care (RMHC) scheme, in a poor rural area of
      China. The study was made possible by a unique longitudinal data set: the total
      sample includes 3492 rural residents from 1020 households. Logistic regression
      was employed for the data analysis. The results show that although this
      subsidized scheme achieved a considerable high enrollment rate of 71% of rural
      residents, adverse selection still exists. In general, individuals with worse
      health status are more likely to enroll in RMHC than individuals with better
      health status. Although the household is set as the enrollment unit for the RMHC
      for the purpose of reducing adverse selection, nearly 1/3 of enrolled households
      are actually only partially enrolled. Furthermore, we found that adverse
      selection mainly occurs in partially enrolled households. The non-enrolled
      individuals in partially enrolled households have the best health status, while
      the enrolled individuals in partially enrolled households have the worst health
      status. Pre-RMHC, medical expenditure for enrolled individuals in partially
      enrolled households was 206.6 yuan per capita per year, which is 1.7 times as
      much as the pre-RMHC medical expenditure for non-enrolled individuals in
      partially enrolled households. The study also reveals that the pre-enrolled
      medical expenditure per capita per year of enrolled individuals was 9.6% higher
      than the pre-enrolled medical expenditure of all residents, including both
      enrolled and non-enrolled individuals. In conclusion, although the subsidized
      RMHC scheme reached a very high enrollment rate and the household is set as the
      enrollment unit for the purpose of reducing adverse selection, adverse selection
      still exists, especially within partially enrolled households. Voluntary RMHC
      will not be financially sustainable if the adverse selection is not fully taken
      into account.

PMID- 16635542
TI  - Effects of Tiron, 4,5-dihydroxy-1,3-benzene disulfonic acid, on human promyelotic
      HL-60 leukemia cell differentiation and death.
AB  - Tiron, 4,5-dihydroxy-1,3-benzene disulfonic acid, has been known to be a widely
      used antioxidant to rescue ROS-evoked cell death and a non-toxic chelator to
      alleviate an acute metal overload. In this study, we showed that Tiron is a
      potent inducer of cell differentiation and apoptotic cell death in human
      promyelotic HL-60 leukemia cell. At a low level of concentration (<0.5mM), Tiron
      caused HL-60 cells to induce differentiation-related alterations such as the
      increase of CD11b and CD14 expression or chromatin condensation. Hypoxia
      inducible factor-1alpha (HIF-1alpha) was also increased at mRNA and protein
      level, and thus the CCAAT/enhancer-binding protein alpha, which is a downstream
      target of HIF-1alpha and acts as a critical factor for granulocytic
      differentiation was increased. High dose of Tiron (>0.5mM) induced severe DNA
      damage in HL-60 cells, as measured by the cytokinesis-block micronucleus test and
      the comet assay. Consequently, high dose of Tiron led to apoptotic cell death,
      which showed the DNA fragmentation, the caspase activation and the unbalance
      between antiapoptotic (Bcl-2) and proapoptotic proteins (Bax). However, an
      exogenous supplement of iron (FeCl(3)) reversed all of these effects, the cell
      differentiation and the apoptotic cell death. Therefore, these results suggest
      that Tiron-mediated differentiation and cell death result from the disturbance of
      iron metabolism.

PMID- 16635543
TI  - Optimization of wastewater treatment alternative selection by hierarchy grey
      relational analysis.
AB  - This paper describes an innovative systematic approach, namely hierarchy grey
      relational analysis for optimal selection of wastewater treatment alternatives,
      based on the application of analytic hierarchy process (AHP) and grey relational
      analysis (GRA). It can be applied for complicated multicriteria decision-making
      to obtain scientific and reasonable results. The effectiveness of this approach
      was verified through a real case study. Four wastewater treatment alternatives
      (A(2)/O, triple oxidation ditch, anaerobic single oxidation ditch and SBR) were
      evaluated and compared against multiple economic, technical and administrative
      performance criteria, including capital cost, operation and maintenance (O and M)
      cost, land area, removal of nitrogenous and phosphorous pollutants, sludge
      disposal effect, stability of plant operation, maturity of technology and
      professional skills required for O and M. The result illustrated that the
      anaerobic single oxidation ditch was the optimal scheme and would obtain the
      maximum general benefits for the wastewater treatment plant to be constructed.

PMID- 16635545
TI  - Object segmentation and recovery via neural oscillators implementing the
      similarity and prior knowledge gestalt rules.
AB  - Object recognition requires the solution of the binding and segmentation
      problems, i.e., grouping different features to achieve a coherent representation.
      Synchronization of neural activity in the gamma-band, associated with gestalt
      perception, has often been proposed as a putative mechanism to solve these
      problems, not only as to low-level processing, but also in higher cortical
      functions. In the present work, a network of Wilson-Cowan oscillators is used to
      segment simultaneous objects, and recover an object from partial or corrupted
      information, by implementing two gestalt rules: similarity and prior knowledge.
      The network consists of H different areas, each devoted to representation of a
      particular feature of the object, according to a topological organization. The
      similarity law is realized via lateral intra-area connections, arranged as a
      "Mexican-hat". Prior knowledge is realized via inter-area connections, which link
      properties belonging to a previously memorized object. A global inhibitor allows
      segmentation of several objects avoiding interference. Simulation results,
      performed using three simultaneous input objects, show that the network is able
      to detect an object even in difficult conditions (i.e., when some features are
      absent or shifted with respect to the original one). Moreover, the trade-off
      between sensitivity (capacity to detect true positives) and specificity (capacity
      to reject false positives) can be controlled acting on the extension of lateral
      synapses (i.e., on the level of accepted similarity). Finally, the network can
      also deal with correlated objects, i.e., objects which have some common features.
      Simulations performed using a different number of objects (2, 3, 4 or 5) suggest
      that the network is able to segment and recall up to four objects, but the
      oscillation frequency must increase, the lower the number of objects
      simultaneously present. The model, although quite simpler compared with
      neurophysiology, may represent a theoretical framework for the analysis of the
      relationships between object representation, memory, learning, and gamma-band
      activity. In particular, it extends previous studies on autoassociative memory
      since it exploits not only oscillatory dynamics, but also a topological
      organization of features.

PMID- 16635546
TI  - Treatment of sewage sludge using electrokinetic geosynthetics.
AB  - The treatment and disposal of sewage sludge is one of the most problematical
      issues affecting wastewater treatment in the developed world. The traditional
      outlets for sewage sludge are to spread it on agricultural land, or to form a
      cake for deposit to landfill or incineration. In order to create a sludge cake,
      water must be removed. Existing dewatering technology based on pressure can only
      remove a very limited amount of this water because of the way in which water is
      bound to the sludge particles or flocs. Several researchers have shown that
      electrokinetic dewatering of sludge is more efficient than conventional
      hydraulically driven methods. This involves the application of a dc voltage
      across the sludge, driving water under an electrical gradient from positive
      (anode) electrode to negative (cathode) electrode. However, there have been
      several reasons why this technique has not been adopted in practice, not least
      because the, normally metallic, anode rapidly dissolves due to the acidic
      environment created by the electrolysis of water. This paper will describe
      experimentation using electrokinetic geosynthetics (EKG): polymer-based materials
      containing conducting elements. These have been used to minimise the problem of
      electrode corrosion and create a sludge treatment system that can produce dry
      solids contents in excess of 30%. It will suggest different options for the
      treatment of sludges both in situ in sludge lagoons and windrows, and ex situ as
      a treatment process.

PMID- 16635547
TI  - Priority of face perception during subliminal stimulation using a new color
      opponent flicker stimulation.
AB  - We developed a new method of color-opponent flicker (COF) stimulation, and
      investigated behavioral responses for object discrimination at the around
      threshold frequency of COF stimulation. Pairs of figures, a face, flower, the
      letter "G" and a random pattern, were drawn with a red and green checkerboard
      with a black mesh. COF stimulation was produced by presenting pairs of figures
      alternately (red-green-red-green-) at various frequencies (30-120 Hz). A
      discrimination task for objects during COF stimulation was performed by 16
      healthy subjects. Threshold frequency of COF stimulation was between 50 and 75
      Hz. The accuracy rate for face discrimination was significantly higher than those
      for other objects (p<0.01, ANOVA with Fisher's PLSD multiple comparisons test).
      The present COF stimulation technique could be useful to investigate subliminal
      processes of the visual system, and the present results indicate a higher
      sensitivity and selectivity for face discrimination than those for other objects.

PMID- 16635548
TI  - Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and
      risk of dementia. The Rotterdam Study.
AB  - Inflammatory mechanisms are involved in the pathogenesis of dementia.
      Inflammatory cytokines, including interleukin-6 (IL-6) and transforming growth
      factor beta1 (TGFbeta1), have been found in association with Alzheimer pathology
      and there is evidence for direct involvement of these cytokines in formation of
      amyloid plaques. Polymorphisms in genes encoding for IL-6 and TGFbeta1 are
      associated with plasma levels of IL-6 and TGFbeta1. Studies examining the
      association between polymorphisms in these genes and dementia yielded conflicting
      results. The purpose of this study was to examine the association between genetic
      variance in IL-6 and TGFbeta1 and risk of dementia. We examined this association
      in the Rotterdam Study, a prospective population-based cohort study in the
      elderly. Polymorphisms in the IL-6 (-174G>C) and TGFbeta1 gene (-800G>A, -509C>T,
      +10T>C, +25G>C and 263C>T) were genotyped and haplotypes of the TGFbeta1 gene
      were constructed. In a random subset IL-6 plasma levels were measured. During
      follow-up (mean 9.2 years), 743 dementia cases were identified. We estimated the
      association between individual polymorphisms and haplotypes with dementia with
      Cox' proportional hazard models. No association was found between the -174G>C
      polymorphism in the IL-6 gene and risk of dementia. No association was found
      between polymorphisms and constructed haplotypes in the TGFbeta1 gene and risk of
      dementia or Alzheimer's disease. No association was found between IL-6 genotype
      and IL-6 plasma levels in the random subset. Associations did not differ across
      APOE genotypes. Our findings do not suggest involvement of genetic variance in IL
      6 and TGFbeta1 in the development of dementia.

PMID- 16635549
TI  - Cellular localization of TRPC5 in the substantia nigra of rat.
AB  - Transient receptor potential channels (TRPC) are plasma membrane, non-selective
      cationic channels and have been proposed as candidates involved in the regulation
      of cellular Ca2+ influx. TRPC are involved in metabotropic glutamate receptor
      (mGluR)-mediated excitatory post-synaptic currents (EPSCs) in the dopaminergic
      neurons of the substantia nigra. We previously observed several subtypes of TRPC
      to be expressed at an mRNA level in the substantia nigra dopamine neurons. In
      particular, TRPC1 and TRPC5 are most frequently expressed in the substantia
      nigra. Our recent immunohistochemical findings showed that TRPC1 are mainly
      distributed in the dendrites of dopamine neurons. In the present study we have
      investigated, by means of immunohistochemistry and dual label immunofluorescence,
      the anatomical distribution of TRPC5 in the substantia nigra, and we have shown
      their preferential localization into the neuronal nuclei. Our findings suggest a
      role of TRPs in the calcium signaling system of the nucleus, although its
      physiological meaning needs further investigations.

PMID- 16635550
TI  - Isolation and primary structures of seven serine proteinase inhibitors from
      Cyclanthera pedata seeds.
AB  - Seven new trypsin inhibitors, CyPTI I-VII, were purified from ripe seeds of
      Cyclanthera pedata by affinity chromatography on immobilized chymotrypsin in the
      presence of 5 M NaCl followed by preparative native PAGE at pH 8.9. The CyPTIs
      (Cyclanthera pedata trypsin inhibitors) belong to a well-known squash inhibitor
      family. They contain 28-30 amino acids and have molecular weights from 3031 to
      3367 Da. All the isolated inhibitors strongly inhibit bovine beta-trypsin
      (K(a)>10(11) M(-1)) and, more weakly, bovine alpha-chymotrypsin (K(a)
      approximately 10(4)-10(6) M(-1)). In the presence of 3 M NaCl the association
      constants of CyPTIs with alpha-chymotrypsin increased a few hundred fold. Taking
      advantage of this phenomenon, a high concentration of NaCl was used to isolate
      the inhibitors by affinity chromatography on immobilized chymotrypsin. It was
      found that although one of them, CyPTI IV, had split the Asn25-Gly26 peptide
      bond, its inhibitory activity remained unchanged. The hydrolyzed bond is located
      downstream of the reactive site. Presumably, the inhibitor is a naturally
      occurring, double-chain protein arising during posttranslational modifications.

PMID- 16635551
TI  - Tissue-engineered peripheral nerve grafting by differentiated bone marrow stromal
      cells.
AB  - Bone marrow stromal cells are multipotential stem cells that contribute to the
      differentiation of tissues such as bone, cartilage, fat and muscle. In the
      experiment, we found that bone marrow stromal cells can be induced to
      differentiate into cells expressing characteristic markers of Schwann cells, such
      as S-100 and glial fibrillary acidic protein, promoting peripheral nerve
      regeneration. Tissue-engineered bioartificial nerve grafting of rats by
      differentiated bone marrow stromal cells was applied for bridging a 10 mm-long
      sciatic nerve defect. Twenty-eight inbred strains of female F344 rats weighing
      160 approximately 200 g were randomly divided into four nerve grafting groups,
      with seven rats in each group. Differentiated bone marrow stromal cell-laden
      group: poly(lactic-co-glycolic) acid tubes with an intrinsic framework were
      seeded with syngeneic bone marrow stromal cells which were induced for 5 days;
      Schwann cell-laden group: poly(lactic-co-glycolic) acid tubes with an intrinsic
      framework were seeded with syngeneic Schwann cells; acellular group: poly(lactic
      co-glycolic) acid tubes were only filled with an intrinsic framework; autografts
      group. Three months later, a series of examinations was performed, including
      electrophysiological methods, walking track analysis, immunohistological staining
      of nerves, immunostaining of S-100 and neurofilament, and axon counts. The
      outcome indicated that bone marrow stromal cells are able to differentiate into
      Schwann-like cells and Schwann-like cells could promote nerve regeneration. Bone
      marrow stromal cells may be potentially optional seed cells for peripheral nerve
      tissue engineering because of abilities of promoting axonal regeneration.

PMID- 16635552
TI  - Meditation and epilepsy: a still hung jury.
AB  - Meditation has been advocated as a treatment for several medical problems,
      including epilepsy. Conversely, concern has been raised that meditation may
      aggravate or even precipitate epilepsy. We present a case of new onset mesial
      temporal lobe epilepsy in a young woman meditator lacking other apparent risk
      factors for epilepsy as a springboard for a balanced discussion concerning the
      potential relationship between meditation and epilepsy, and a criticism of the
      current literature in this field. Prospective clinical studies of meditators with
      video-electroencephalography and clinical trials of meditation in refractory
      epilepsy patients are needed to resolve current controversies concerning
      meditation and epilepsy.

PMID- 16635553
TI  - Different inflammatory response and oxidative stress in neointimal hyperplasia
      after balloon angioplasty and stent implantation in cholesterol-fed rabbits.
AB  - Inflammatory responses appear to play an important role in the occurrence of
      restenosis following coronary intervention. However, the contribution of C
      reactive protein (CRP) and oxidative stress to restenosis after balloon
      angioplasty and stent implantation remains unclear. The aim of this study was to
      examine this issue using hyperlipidemic rabbits. Rabbits were divided into two
      groups; they were fed with a 0.5% cholesterol diet and with a mixed 0.5%
      cholesterol and 0.5% probucol diet. Each group of rabbits underwent balloon
      injury and stent implantation in right and left iliac arteries, respectively.
      Eight weeks after the intervention, we examined luminal stenosis, neointimal
      hyperplasia, immunoreactivity for macrophage, CRP and oxidized
      phosphatidylcholine (oxPC), and also the expression of CRP mRNA. The degrees of
      neointimal hyperplasia and immunopositive areas (%) for macrophage, CRP, and oxPC
      in the neointima were significantly higher after stent implantation than after
      balloon injury, but CRP mRNA was undetectable in either artery. Anti-oxidant
      probucol reduced angiographic stenosis, neointimal hyperplasia, and macrophage-
      and oxPC-positive areas much more significantly after stenting. The results
      demonstrate that the inflammatory response to the development of neointimal
      hyperplasia differs after balloon injury and stent implantation and that CRP
      deposition and oxidative stress might be involved more significantly in
      neointimal development after stent implantation.

PMID- 16635554
TI  - Freshly prepared immune complexes with intermittent microwave irradiation result
      in rapid and high-quality immunostaining.
AB  - We have previously reported that intermittent microwave irradiation shortened the
      primary or secondary antibody incubation time to 10 min in a special moist
      chamber. To achieve precise immunostaining within 1h, we attempted to generate a
      novel procedure, "freshly prepared immune complex with intermittent microwave
      irradiation (f-IC-M)". The advantage of this immunostaining procedure lies in a
      one-step incubation instead of primary and then secondary antibody application.
      In this study, we employed five primary antibodies to examine the efficiency and
      quality of this procedure. As expected, every primary antibody examined brought
      about precise immunostaining within 45 min for formalin-fixed, paraffin-embedded
      sections, and within 15 min for frozen sections. In addition, this procedure is
      able to generate double-immunoenzymatic staining with different enzyme-labeled
      primary antibodies if desired. As any combination of primary and secondary
      antibodies is possible by this one-step application, f-IC-M increases the
      efficiency of immunostaining without losing quality. Therefore, this procedure is
      able to rapidly provide diagnostic information to the pathologists.

PMID- 16635555
TI  - Cloning and expression analysis of an ovine PAP-like protein cDNA, a gene
      differentially expressed in scrapie.
AB  - In a previous study, the mRNA level of a pancreatitis-associated protein (PAP)
      like protein was found to be elevated in the ileal Peyer's patch of lambs during
      the early phase of scrapie infection. Here, we report the isolation of the ovine
      PAP-like protein cDNA which encodes a putative 178 amino acid protein with a
      signal peptide and a C-lectin binding domain. Comparisons of REG/PAP proteins
      between various species showed that the deduced amino acid sequences were
      conserved. The overall amino acid identity between the ovine PAP-like protein and
      bovine, human and rat REG/PAP proteins varied from 23% to 85%. In Northern blot
      analysis the expression of the ovine PAP-like protein mRNA was restricted to the
      ileal and jejunal Peyer's patches. The cellular expression of the PAP-like
      protein mRNA in the ovine intestine was further characterized by in situ
      hybridization. PAP-like protein mRNA was detected in cells of the epithelial
      lining in most crypts and in some intestinal villi in the ileum and jejunum while
      in the colon and rectum, the PAP-like protein mRNA expression was only detected
      in the deep portion of a few crypts. The data provided will offer the possibility
      to search for a link between this PAP-like protein and early events in the
      development of scrapie.

PMID- 16635556
TI  - Response to comments by Vladimir Murashov.
AB  - Dr. Murashov has emphasized the major objective of our paper, which shows that
      exposure of growing plant roots to nanoparticles of alumina may result in growth
      inhibition and that this effect appears to be related to surface characteristics
      of the particles. The paper indicates that the mechanism(s) by which the
      particles may induce growth inhibition needs further attention. We agree that it
      is premature to draw definitive conclusions about toxicity mechanisms.

PMID- 16635557
TI  - Antiplasmodial activity of Cylicodiscus gabunensis.
AB  - The antimalarial activity of ethanolic stembark extract of Cylicodiscus
      gabunensis was studied in vivo in mice infected with Plasmodium berghei berghei
      during early and established infections as well as for repository activity. The
      LD(50) of the extract was determined to be 223.6 mg/kg, while doses of 250 mg/kg
      and above were found to be lethal to mice. Cylicodiscus gabunensis extract (20-60
      mg/kg/day) exhibited a significant (P<0.05) blood schizontocidal activity in 4
      day early infection, repository evaluation and in established infection with a
      significant mean survival time comparable to that of the standard drug,
      chloroquine, 5 mg/kg/day. The stembark extract possesses a promising
      antiplasmodial activity, which can be exploited in malaria therapy.

PMID- 16635558
TI  - Inhibitory effects of Euterpe oleracea Mart. on nitric oxide production and iNOS
      expression.
AB  - The palm Euterpe oleracea is a plant of great economic value in Brazil. Although
      the heart of palm extracted from its trunk is considered a delicacy the world
      over, its fruits are popular only among Brazilians. In some poor regions of
      Brazil, there are reports on the popular use of its juice in the treatment of
      several disorders, mainly those of oxidative onset as cardiovascular ones.
      Because of its wide utilization; because there are very few scientific studies of
      this species, and to discover if its use in folk medicine for problems related
      with oxidation is in fact justifiable, we decided, in this study, to evaluate the
      effects of Euterpe oleracea flowers, fruits and spikes fractions on: nitric oxide
      (NO) production, NO scavenger capacity, and on the expression of inducible nitric
      oxide synthase enzyme, as well. Results showed that the fractions obtained from
      fruits were the most potent in inhibiting NO production, followed by those from
      flowers and spikes. Only in high doses, did some fractions reduce cell viability.
      Reduction on NO production was not due to NO scavenger activity. These results
      were accompanied by inhibition of iNOS expression. The more pronounced effect was
      observed in the fractions in which the concentration of cyanidin-3-O-glucoside
      and cyanidin-3-O-rhamnoside were higher. To sum up, our results indicate that
      fractions from Euterpe oleracea inhibits NO production by reducing the levels of
      inducible nitric oxide synthase expression.

PMID- 16635559
TI  - Pretreatment attrition and childhood social phobia: Parental concerns about
      medication.
AB  - Pretreatment attrition, the systematic self-exclusion of potential participants
      during the recruitment phase of a study, poses a significant threat to the
      external validity of randomized clinical trials. Very little is known about the
      factors that contribute to pretreatment attrition, especially among families
      seeking treatment for a child. The current study assessed pretreatment attrition
      in a randomized clinical trial of behavior therapy, fluoxetine, and placebo for
      child and adolescent social phobia. Reluctance toward medication treatment
      accounted for 44.7% of study refusals and was disproportionately common among
      ethnic minority families. Parents were particularly worried about the potential
      for side effects or physical/psychological dependency upon the medication.
      Results are discussed in terms of the implications for external validity in
      future psychopharmacological clinical trials.

PMID- 16635560
TI  - Breast milk provides better antioxidant power than does formula.
AB  - OBJECTIVE: We examined the effect of breast milk on plasma total antioxidant
      capacity (TAC), total peroxide (TP), and oxidative stress index (OSI), which are
      biomarkers of oxidative status. METHODS: Fifty-four healthy term infants 3 to 6
      mo of age were fed breast milk or a cow's milk modified formula. Plasma TAC,
      vitamin C, albumin, bilirubin, and uric acid levels were measured as indexes of
      antioxidative markers. Plasma TP levels were measured as an oxidative stress
      marker. The OSI was calculated to assess oxidative status. RESULTS: No
      significant differences were observed between groups with respect to growth or
      anthropometric measurements. Plasma uric acid, total protein, and albumin
      concentrations were slightly higher in the breast-fed group than in the formula
      fed group. There was a positive correlation between infant's age and serum
      albumin levels; between TAC and plasma uric acid, albumin, and total bilirubin;
      and between plasma iron and TP levels in both groups (r > 0.256, P < 0.05). In
      addition, there was a negative correlation between plasma iron and TAC (r = 
      0.267, P = 0.01). Plasma TAC and vitamin C levels were significantly higher in
      the breast-fed group than in the formula-fed group (P < 0.05). Plasma TP levels
      and the OSI were higher in the formula-fed group than those in the breast-fed
      group (P < 0.05). CONCLUSIONS: Our data suggest that breast milk provides better
      antioxidant power than does formula.

PMID- 16635561
TI  - Assessing elderly at risk of malnutrition: the new Geriatric Nutritional Risk
      Index versus Nutritional Risk Index.

PMID- 16635562
TI  - Effect of dietary argan oil on fatty acid composition, proliferation, and
      phospholipase D activity of rat thymocytes.
AB  - OBJECTIVE: Argan oil is receiving increasing attention due to its potential
      health benefits in the prevention of cardiovascular risk, but no information to
      date is available about its possible effect on immune cells and functions.
      METHODS: To address this issue male rats were fed one of five diets that
      contained fish oil, argan oil, olive oil, coconut oil, or sunflower oil for 4 wk.
      The fatty acid composition of plasma and thymocyte lipids was then analyzed in
      relation to the mitogen-induced proliferation and phospholipase D (PLD) activity
      of thymocytes. RESULTS: The 18:2omega-6 proportion in thymocyte phospholipids
      from rats fed argan oil was significantly lower than that observed in
      phospholipids from rats fed sunflower oil and fish oil but higher than that found
      in the olive oil and coconut oil groups. Further, a significant positive linear
      relation was found between thymocyte proliferation and the 18:2omega-6 proportion
      in thymocyte phospholipids, whatever the diet. The proliferation response of
      thymocytes to mitogenic activation was also inversely correlated to PLD activity
      measured in intact thymocytes. Subsequent western blotting experiments indicated
      that the diet-induced variations in PLD activity mainly reflected variations in
      the expression of PLD2 protein. CONCLUSIONS: On the whole, the present study
      shows that the effects of argan oil on immune cells are very similar to those of
      olive oil, and that, as a consequence, argan oil can be used as a balanced
      dietary supply without marked adverse effects on immune cell function.

PMID- 16635563
TI  - Selective induction of inducible nitric oxide synthase in pancreatic islet of rat
      after an intravenous glucose or intralipid challenge.
AB  - OBJECTIVE: Constant exposure of pancreatic islets to high levels of glucose or
      free fatty acids can lead to irreversible beta-cell dysfunction, a process
      referred to as glucotoxicity or lipotoxicity, respectively. In this context a
      role for nitric oxide generated by pancreatic islet has been suggested. The
      present investigation examined whether the route of glucose administration, i.e.,
      given orally (OG) or infused intravenously (IVG), could have any effect on the
      expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic
      islets. METHODS: Rats were infused with glucose (50%) or Intralipid intravenously
      for 24 h or given glucose orally. A freely fed control group (FF) was also
      included. At 24 h rats were killed and blood samples were drawn for analysis of
      plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each
      animal and investigated for the occurrence of iNOS by the use of confocal
      microscopy, western blot, and high-performance liquid chromatographic analysis.
      The effect of intravenously infused glucose was then compared with the effect of
      an intravenous infusion of Intralipid (IL). RESULTS: Plasma insulin levels were
      markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid
      (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels
      were markedly increased in the IVG group, whereas both parameters were decreased
      in the IL group. No significant differences in plasma insulin, glucagon, or
      glucose were found between the OG and FF groups. Immunocytochemical (confocal
      microscopy), western blot, and biochemical (high-performance liquid
      chromatographic) analyses showed that a sustained increase in plasma level of
      glucose or free fatty acids by an intravenous infusion of either nutrient for 24
      h resulted in a marked expression and activity of iNOS in pancreatic islets. No
      sign of iNOS expression could, however, be detected in the islets of FF control
      or OG rats. CONCLUSION: The data suggest that impaired beta-cell function found
      after 24 h of an intravenous infusion of glucose or Intralipid might be mediated,
      at least in part, by the induction of iNOS in pancreatic islets. This may
      subsequently result in an exclusive production of nitric oxide, which is
      deleterious for beta-cells.

PMID- 16635564
TI  - Effect of retinol on iron bioavailability from Iranian bread in a Caco-2 cell
      culture model.
AB  - OBJECTIVE: Iron and vitamin A deficiencies are among the most prevalent
      nutritional problems. There are no data on iron bioavailability in Iran. In
      addition, interaction of vitamin A with iron bioavailability is not well
      documented, so we determined iron bioavailability from the most widely consumed
      food in Iran, lavash bread, and the effect of vitamin A on this bioavailability.
      METHODS: In vivo human studies for determining iron bioavailability are
      cumbersome, time consuming, and costly to perform, so we used an in vitro model
      in Caco-2 cells. Bread samples were digested with or without vitamin A (10
      microg/1.0 g of dried bread). We used an iron solution containing vitamin C as a
      positive control. Iron absorption was measured using 59FeCl3. Bioavailability was
      defined as the percentage of radiolabeled iron taken up and transferred by Caco-2
      cells after 1.5 h of incubation. Experiments were carried out two to four times.
      RESULTS: Mean +/- standard deviations for iron bioavailability in bread samples
      digested without or with additional vitamin A and in controls were 2.53 +/-
      1.55%, 6.62 +/- 3.40%, and 20.80 +/- 2.30%, respectively (P < 0.001). Vitamin A
      caused a 2.62-fold increase in iron absorption from bread samples. CONCLUSIONS:
      Iranian lavash bread has low iron bioavailability, but this can be increased by
      vitamin A supplementation. Increasing vitamin A intake can be considered as a
      method for increasing iron bioavailability, thus combating iron and vitamin A
      deficiencies simultaneously.

PMID- 16635565
TI  - Body composition and resting energy expenditure in elderly male patients with
      chronic obstructive pulmonary disease.
AB  - STUDY OBJECTIVE: Our study investigates nutritional status, resting energy
      expenditure (REE) and physical performance in elderly patients with stable COPD
      to identify any early conditions of hypermetabolism, malnutrition and sarcopenia.
      METHODS: Eighty-six males (40 stable COPD and 46 healthy subjects) over 65 years
      old were studied. All subjects underwent spirometry, blood gas analysis and a 6
      min walking test (6MWT). Fat-free mass (FFM) and appendicular skeletal muscle
      mass (ASMM) were measured by dual energy X-ray absorptiometry (DEXA). REE was
      measured by indirect calorimetry. RESULTS: COPD patients had a lower FFM both
      expressed in kilograms and after correction for height squared. The prevalence of
      sarcopenia was higher for COPD subjects (38% vs 31%). REE, both in absolute
      values and adjusted for FFM was significantly higher in COPD patients.
      Hypermetabolism was found in 60% of COPD cases and 13.7% (P<0.01) of healthy
      subjects. No relationship was found in COPD patients between the
      measured/predicted REE ratio (REE(m)/REE(p)) and FEV1. In the hypermetabolic COPD
      subgroup, the REE(m)/REE(p) ratio correlated with 6MWT. CONCLUSIONS: Elderly
      patients with stable COPD develop an increased REE. This hypermetabolism seems to
      be independent of the severity of the pulmonary obstruction and to influence the
      patient's physical performance.

PMID- 16635566
TI  - Evaluating the pharmacoeconomic effect of adding tiotropium bromide to the
      management of chronic obstructive pulmonary disease patients in Singapore.
AB  - OBJECTIVE: To perform a pharmacoeconomic analysis on the treatment of chronic
      obstructive pulmonary disease (COPD) with the addition of tiotropium bromide.
      METHODS: Pharmacoeconomic modeling was performed utilizing the efficacy of
      tiotropium bromide from the literature on different settings and severity of
      COPD. Reductions in exacerbations, hospitalizations, and number of exacerbation
      days per year were derived from these studies. Cost of drug treatment,
      exacerbations, hospitalization, and loss of income were derived from local data
      in Singapore and reported in Singapore dollars (US$1=S$1.71). A model was
      constructed to calculate the impact of one-year treatment with tiotropium
      bromide, and the results were reported for the total incremental cost per year,
      cost per year needed to reduce one hospitalization in one year, and cost-savings
      from hospitalizations in one year. Sensitivity analysis were performed for
      different number of patients treated per year, differing cost of hospitalization,
      different cost for tiotropium bromide, different impact of tiotropium bromide on
      clinical outcomes, and the different amount of substitution drug utilized in the
      comparator group. RESULTS: Using the different clinical effects and looking at
      the impact on treating 1000, 2000, and 10,000 patients per year, most of the
      results showed a high level of decrease in overall cost per year that ranged from
      S$145.40 to S$840.37 per patient treated. Cost per year needed to reduce one
      hospitalization in one year ranged from S$3217.31 to S$18,148.92. Cost-savings
      from hospitalizations in one year per patient treated ranged from $57.16 to
      $322.49. This may contribute as high as 83% of the overall cost saving.
      Sensitivity analysis supports the cost savings finding. CONCLUSION: Adding
      tiotropium bromide for severe COPD patients would lead to a significant cost
      savings for the economy.

PMID- 16635567
TI  - Lipoate-based imprinted self-assembled molecular thin films for biosensor
      applications.
AB  - Lipoate derivatives were used for the formation of imprinted self-assembled
      molecular thin films for the recognition of morphine. A large collection of
      lipoate derivatives was screened by molecular dynamics simulations in various
      solvents. A set of ligands showing favourable interactions with morphine in
      aqueous environment was selected for synthesis. Morphine-imprinted layers were
      then produced on gold substrates in mixed monolayers with morphine added as the
      template. The binding of ligands and morphine to gold, as well as the
      association/dissociation of morphine to the formed layers were studied with
      Surface Plasmon Resonance. Imprinted factors were highly variable and were
      dependent on ligand/morphine mixing ratio, lipoate derivative and monolayer
      preparation method. The imprinted factors were as high as 100 and 600 for one of
      the ligands. The results show that the simulations are able to provide correct
      information of the relative strengths of the molecular interactions between the
      ligand and morphine molecules in different solutions. The liquid phase
      simulations are, however, not able to predict the imprinted factors (i.e.
      distinguish between specific and non-specific binding), because the specificity
      is not formed before self-assembly on the surface.

PMID- 16635568
TI  - Quantitative and simultaneous detection of four foodborne bacterial pathogens
      with a multi-channel SPR sensor.
AB  - We report the quantitative and simultaneous detection of four species of
      bacteria, Escherichia coli O157:H7, Salmonella choleraesuis serotype typhimurium,
      Listeria monocytogenes, and Campylobacter jejuni, using an eight-channel surface
      plasmon resonance (SPR) sensor based on wavelength division multiplexing.
      Detection curves showing SPR response versus analyte concentration were
      established for each species of bacteria in buffer at pH 7.4, apple juice at
      native pH 3.7, and apple juice at an adjusted pH of 7.4, as well as for a mixture
      containing all four species of bacteria in buffer. Control experiments were
      performed to show the non-fouling characteristics of the sensor surface as well
      as the specificity of the amplification antibodies used in this study. The limit
      of detection (LOD) for each of the four species of bacteria in the tested
      matrices ranges from 3.4 x 10(3) to 1.2 x 10(5) cfu/ml. Detection curves in
      buffer of an individual species of bacteria in a mixture of all four species of
      bacteria correlated well with detection curves of the individual species of
      bacteria alone. SPR responses were higher for bacteria in apple juice at pH 7.4
      than in apple juice at pH 3.7. This difference in sensor response could be partly
      attributed to the pH dependence of antibody-antigen binding.

PMID- 16635569
TI  - Microsystem for transfection of exogenous molecules with spatio-temporal control
      into adherent cells.
AB  - Several non-viral techniques involving the use of liposomes, particle bombardment
      and electroporation have been used for efficient transfection of plasmids and
      other molecules into cells. Current approaches target whole or bulk regions of
      tissue, lacking the desired spatial control over the transfection process. In
      this study, we present a novel approach using microsystems to achieve spatial and
      temporal control over the transfection process in adherent cells. A 6x6 MEA
      (microelectrode array) with 100 microm microelectrode dimension was developed on
      a silicon substrate using standard microfabrication procedures and passivated
      with a biocompatible layer. Using finite element models, electric field
      intensities were simulated and locations of optimal electroporation zones in the
      cell culture on the microelectrode surface were predicted. The MEA was
      subsequently tested using 3T3 fibroblasts cultured on the MEA surface for 96 h
      and stimulation voltages in the range of 2-5 V in the presence of propidium
      iodide (PI), a cell impermeant dye. Maximum electric field intensities in the z
      direction were estimated to be in the range of 320-820 V/cm for applied
      differential voltages in the range of 2-5 V. Cells directly on the top and on the
      edges of the stimulating microelectrodes in the MEA were preferentially
      transfected with PI as predicted by the simulations. The results of these
      experiments demonstrate that spatial and temporal control of desired regions of
      transfection in vitro can be achieved using MEAs and electroporation.

PMID- 16635570
TI  - Sorption of Cr(III) onto chelating b-DAEG-sporopollenin and CEP-sporopollenin
      resins.
AB  - In the present study, the removal of Cr(III) from aqueous solution was studied
      using a new chelate-resins (b-DAEG-sporopollenin and CEP-sporopollenin).
      Mechanisms including ion exchange, complexation and adsorption to the surface are
      possible in the sorption process. Adsorption analysis results obtained at various
      concentrations of Cr(III) showed that the adsorption pattern on the resin
      followed a Langmuir isotherm. Langmuir constant Gamma max and k for Cr(III) were
      found as 1.23, 84.84 mmol/g for b-DAEG-sporopollenin, 133.33, 10.39 mmol/g for
      CEP-sporopollenin at 20 +/- 1 degrees C, respectively. In addition, kinetic and
      thermodynamic parameters such as enthalpy (DeltaH0), free energy (DeltaG0) and
      entropy (DeltaS0) were calculated and these values show that adsorption of
      Cr(III) on b-DAEG-sporopollenin and CEP-sporopollenin was an exothermic process
      and the process of adsorption was favored at high temperatures. Maximum Cr(III)
      removal was observed near a pH of 6.

PMID- 16635571
TI  - Characterization of food waste as feedstock for anaerobic digestion.
AB  - Food waste collected in the City of San Francisco, California, was characterized
      for its potential for use as a feedstock for anaerobic digestion processes. The
      daily and weekly variations of food waste composition over a two-month period
      were measured. The anaerobic digestibility and biogas and methane yields of the
      food waste were evaluated using batch anaerobic digestion tests performed at 50
      degrees C. The daily average moisture content (MC) and the ratio of volatile
      solids to total solids (VS/TS) determined from a week-long sampling were 70% and
      83%, respectively, while the weekly average MC and VS/TS were 74% and 87%,
      respectively. The nutrient content analysis showed that the food waste contained
      well balanced nutrients for anaerobic microorganisms. The methane yield was
      determined to be 348 and 435 mL/gVS, respectively, after 10 and 28 days of
      digestion. The average methane content of biogas was 73%. The average VS
      destruction was 81% at the end of the 28-day digestion test. The results of this
      study indicate that the food waste is a highly desirable substrate for anaerobic
      digesters with regards to its high biodegradability and methane yield.

PMID- 16635572
TI  - Modified Dejour trochleoplasty for severe dysplasia: operative technique and
      early clinical results.
AB  - Instability of the patella occurs when it fails to track fully in the femoral
      groove during knee movement. The groove begins at the metaphysis of the distal
      femur and extends on its anterior surface inferiorly to the femoral notch. It is
      normally present at birth and the cartilaginous shape is similar to that of the
      adult. An abnormal trochlea may be shallow. In extreme cases it may be dome
      shaped, where it is associated with recurrent subluxation or dislocation of the
      patella. In these cases it is logical to consider fashioning a groove as part of
      a realignment procedure. This study reports the operative technique and early
      clinical and radiological results of a consecutive case series of the first 15
      patients (17 knees) who underwent a deepening trochleoplasty for severe dysplasia
      developed from that described by Dejour. The follow-up was for a minimum of 1
      year (average 3 years, range 1 to 9 years). The boss height was reduced from an
      average of 7.5 mm (range 6 to 11 mm) to 0.7 mm (range -1 to 3 mm). Tracking
      became normal in 11 knees and had a slight J-shaped in six. Seven knees had mild
      residual apprehension. Seven patients were very satisfied, six were satisfied,
      and two were disappointed. The Kujala score improved from an average of 48 (range
      13 to 75) to 75 (range 51 to 98) out of 100 (p<0.05). Three patients returned to
      full sports. Eight patients required further operations apart from the removal of
      metallic screws in 10 knees. Five of these were arthroscopic arthrolysis for
      stiffness at about 6 weeks post-operatively. Trochleoplasty for severe dysplasia
      of the femoral sulcus is a developing procedure. It requires careful attention to
      detail. For a rare condition the early results have been satisfactory with an
      acceptable level of complications.

PMID- 16635573
TI  - Reliability of a technique for determining sagittal knee geometry from lateral
      knee radiographs.
AB  - The purposes of this study were to describe an analytical technique for
      determining selected 2-dimensional geometric characteristics of a knee joint
      using lateral knee radiographs and to examine the inter- and intra-analyst
      reliability of this technique. Five lateral knee radiographs of different knee
      flexion angles (25-85 degrees at intervals of 15 degrees ) were obtained from
      five subjects. Two graduate and five undergraduate students with knowledge of
      knee anatomy served as the analysts and were asked to identify certain landmarks
      from the radiographs. The coordinates of these landmarks were used to determine
      the effective moment arm of the quadriceps force, patellar tendon length, patella
      height, patellar mechanism and patellar tendon angles, and tibiofemoral and
      patellofemoral joint spaces. For each radiograph, intraclass correlation
      coefficients (ICCs) were computed for combinations of 2-7 analysts. Using all
      seven analysts, the ICCs ranged from 0.9967 to 0.9985 for different radiographs.
      When fewer analysts were used, the average ICCs were 0.9975 (6 analysts), 0.9974
      (5 analysts), 0.9974 (4 analysts), 0.9974 (3 analysts), and 0.9973 (2 analysts).
      Four of the analysts re-analyzed the radiographs 2-3months after the initial
      analyses. Intra-analyst ICCs ranged from 0.9842 to 0.9999. Overall, the high ICC
      values indicate excellent inter- and intra-analyst reliability. The proposed
      technique is reliable and may be used for both clinical and research purposes.
      The relatively small reductions in ICCs when fewer analysts were used suggest
      that a single experienced analyst is sufficient for clinical assessment. However,
      2-3 analysts are recommended for research purposes.

PMID- 16635574
TI  - Synthesis and biological evaluation of linear phenylethynylbenzenesulfonamide
      regioisomers as cyclooxygenase-1/-2 (COX-1/-2) inhibitors.
AB  - A group of regioisomeric phenylethynylbenzenesulfonamides possessing a COX-2
      SO2NH2 pharmacophore at the para-, meta- or ortho-position of the C-1 phenyl
      ring, in conjunction with a C-2 substituted-phenyl (H, OMe, OH, Me, F) group,
      were synthesized and evaluated as inhibitors of the cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) isozymes. The target 1,2-diphenylacetylenes were
      synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. In
      vitro COX-1/-2 isozyme inhibition structure-activity data showed that COX-1/-2
      inhibition and the COX selectivity index (SI) are sensitive to the regioisomeric
      placement of the COX-2 SO2NH2 pharmacophore where the COX-2 potency order for the
      benzenesulfonamide regioisomers was generally meta>para and ortho. Among this
      group of compounds, the in vitro COX-1/-2 isozyme inhibition studies identified 3
      (2-phenylethynyl)benzenesulfonamide (10a) as a COX-2 inhibitor (COX-2 IC50=0.45
      microM) with a good COX-2 selectivity (COX-2 SI=70). In contrast, 2-[2-(3
      fluorophenyl)ethynyl]benzenesulfonamide (11c) possessing a SO2NH2 COX-2
      pharmacophore at the ortho-position of the C-1 phenyl ring exhibited COX-1
      inhibition and selectivity (COX-1 IC50=3.6 microM). A molecular modeling study
      where 10a was docked in the binding site of COX-2 shows that the meta-SO2NH2 COX
      2 pharmacophore was inserted inside the COX-2 secondary pocket (Arg513, Phe518,
      Val523, and His90). Similar docking of 10a within the COX-1 binding site shows
      that the meta-SO2NH2 pharmacophore is unable to interact with the respective
      amino acid residues in COX-1 that correspond to those near the secondary pocket
      in COX-2 due to the presence of the larger Ile523 in COX-1 that replaces Val523
      in COX-2.

PMID- 16635575
TI  - Transgenic expression of human FGF-1 protects against hypoxic-ischemic injury in
      perinatal brain by intervening at caspase-XIAP signaling cascades.
AB  - Perinatal hypoxia-ischemia (HI) is a major cause of neurological disability and
      mortality in infant and children. In the present study, we explored the
      neuroprotective efficacy of FGF-1 in a rat model of perinatal HI. Carotid
      ligation combined with hypoxia caused marked infarctions in the ipsilateral
      cerebral hemisphere with significant loss of ipsilateral striatal, cortical and
      hippocampal volumes. Morphological analyses revealed both apoptotic and necrotic
      form of neuronal death determined by Nissl histology, dark-field microscopy and
      TUNEL staining. HI induced a marked increase in activated caspase-9, caspase-3
      and PARP cleavage at 12 h to 7 days after HI in brain areas displaying TUNEL (+)
      cells. In addition, expression of the anti-apoptotic protein X-linked inhibitor
      of apoptosis (XIAP) was decreased under similar conditions of HI. Expression of
      human FGF-1 in brain significantly reduced the extent of both apoptotic and
      necrotic injury caused by HI. FGF-1 attenuated the HI-induced increase in
      activated caspase-3, caspase-9 and cleaved PARP protein levels and markedly
      blocked the HI-induced decrease in XIAP expression under the conditions at which
      FGF-1 showed significant neuroprotection. These findings demonstrate that FGF-1
      prevents the onset of both apoptotic and necrotic death in neurons otherwise
      "destined to die" following hypoxic-ischemic injury by intervening at the level
      of caspase-signaling cascades and by restoring prosurvival protein XIAP
      expression in central neurons.

PMID- 16635577
TI  - Caffeine reduces the initial dip in the visual BOLD response at 3 T.
AB  - Localized changes in oxygen consumption related to increased neural activity can
      result in a small and transient "initial dip" of the blood oxygenation level
      dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). The
      initial dip has been of great interest to the fMRI community because it may
      provide a more accurate and localized measure of neural activity than the
      conventional BOLD signal increase. Although potentially useful as a technique for
      human brain mapping, the initial dip is not always detected and has been a source
      of some controversy. In this study, the BOLD response to a 4-s long visual
      stimulus was measured with a 3-T MRI system in 5 healthy volunteers both before
      and immediately after a 200-mg oral caffeine dose. The caffeine dose
      significantly (P < 0.001) reduced or eliminated the initial dip in all subjects.
      These findings suggest that caffeine usage may be a key factor in the detection
      of the initial dip in human fMRI studies.

PMID- 16635578
TI  - Divide and conquer: a defense of functional localizers.
AB  - Numerous functionally distinct regions of cortex (e.g., V1, MT, the fusiform face
      area) can be easily identified in any normal human subject in just a few minutes
      of fMRI scanning. However, the locations of these regions vary across subjects.
      Investigations of these regions have therefore often used a functional region of
      interest (fROI) approach in which the region is first identified functionally in
      each subject individually, before subsequent scans in the same subjects test
      specific hypotheses concerning that region. This fROI method, which resembled
      long-established practice in visual neurophysiology, has methodological,
      statistical, and theoretical advantages over standard alternatives (such as whole
      brain analyses of group data): (i) because functional properties are more
      consistently and robustly associated with fROIs than with locations in
      stereotaxic space, functional hypotheses concerning fROIs are often the most
      straightforward to frame, motivate, and test, (ii) because hypotheses are tested
      in only a handful of fROIs (instead of in tens of thousands of voxels), advance
      specification of fROIs provides a massive increase in statistical power over
      whole-brain analyses, and (iii) some fROIs may serve as candidate distinct
      components of the mind/brain worth investigation as such. Of course fROIs can be
      productively used in conjunction with other complementary methods. Here, we
      explain the motivation for and advantages of the fROI approach, and we rebut the
      criticism of this method offered by Friston et al. (Friston, K., Rotshtein, P.,
      Geng, J., Sterzer, P., Henson, R., in press. A critique of functional localizers.
      NeuroImage).

PMID- 16635579
TI  - A critique of functional localisers.
AB  - In this critique, we review the usefulness of functional localising scans in
      functional MRI studies. We consider their conceptual motivations and the
      implications for experimental design and inference. Functional localisers can
      often be viewed as acquiring data from cells that have been removed from an
      implicit factorial design. This perspective reveals their potentially restrictive
      nature. We deconstruct two examples from the recent literature to highlight the
      key issues. We conclude that localiser scans can be unnecessary and, in some
      instances, lead to a biased and inappropriately constrained characterisation of
      functional anatomy.

PMID- 16635580
TI  - Evolutionary history of woodpeckers and allies (Aves: Picidae): placing key taxa
      on the phylogenetic tree.
AB  - We analyzed 2995 base pairs of nucleotide sequence data (nuclear beta-fibrinogen
      intron 7 and mitochondrial cytochrome b and ND2 genes), using parsimony and model
      based approaches to infer phylogenetic relationships of the woodpeckers and
      allies, yielding novel hypotheses for several critical gaps in the knowledge of
      picid phylogeny. We tested the monophyly of sub-families within the Picidae, and
      sampled from widely distributed and diverse genera (Celeus, Colaptes, Dryocopus,
      Melanerpes, Picoides, Picumnus, Sasia, Piculus, and Picus). Relationships of
      three poorly known Southeast Asian genera (Dinopium, Reinwardtipicus, and
      Blythipicus) were also examined, revealing unexpected sister relationships. All
      phylogenetic approaches recovered largely congruent topologies, supporting a
      monophyletic Picinae and paraphyletic Picumninae, with the monotypic piculet,
      Nesoctites micromegas, as sister to the Picinae. We report paraphyly for Celeus
      and Piculus, whereas the broadly distributed genera Picumnus and Dryocopus were
      supported as monophyletic. Our phylogenetic results indicate a complex geographic
      history for the Picidae, with multiple disjunct sister lineages distributed
      between the New World and Asia. The relationships and geographic distribution of
      basal picid lineages indicates an Old World origin of the Picidae; however, the
      geographic origin of the Picinae remains equivocal, as the sister relationship
      between the Caribbean N. micromegas and the true woodpeckers presents the
      possibility of a New World origin for the Picinae.

PMID- 16635581
TI  - Diffusion tensor imaging of articular cartilage as a measure of tissue
      microstructure.
AB  - OBJECTIVE: To use diffusion tensor MR micro-imaging to observe differences in
      magnitude and anisotropy of water diffusion between 'healthy' cartilage and
      cartilage enzymatically degraded to simulate arthritic damage. METHODS: Diffusion
      tensor images (156 x 156 microm in-plane resolution, 2mm slice thickness) of
      bovine cartilage were obtained at either 4.7 or 7.0 T using pulsed field gradient
      spin echo sequences. The parameters determined were: maximum and mean
      diffusivity, direction of the maximum diffusion eigenvector with respect to the
      normal to the articular surface and fractional anisotropy (FA) of diffusion.
      RESULTS: Both maximum and mean diffusion eigenvalues were found to decrease,
      respectively, from approximately 1.95 x 10(-9) and 1.80 x 10(-9) m2 s(-1) at the
      articular surface to approximately 1.08 x 10(-9) and 0.79 x 10(-9) m2 s(-1) in
      the deep zone. A systematic change was observed in the direction of the
      eigenvector corresponding to maximum diffusivity, reflecting the expected change
      in orientation of the collagen macrofibrillar bundles. Degradation with trypsin
      to remove proteoglycans resulted in a 10-15% increase in apparent diffusion
      coefficient of water in the cartilage, with no apparent change in FA.
      CONCLUSIONS: These methods have the potential to be used to probe local changes
      in tissue microstructure and the hydrodynamic status of cartilage during
      development of osteoarthritis.

PMID- 16635582
TI  - Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of
      the ankle: a prospective study.
AB  - OBJECTIVE: To investigate the efficacy, safety and the duration of treatment
      effectiveness of intra-articular hyaluronic acid (Artz, Japan) in patients with
      ankle osteoarthritis (OA). METHOD: As a prospective clinical trial, 93 patients
      with unilateral ankle pain for at least 6 months and radiographically classified
      as Kellgren-Lawrence grade I or II ankle OA were included. After five weekly
      intra-articular Artz injections, the Ankle Osteoarthritis Scale (AOS), the
      American Orthopaedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, ankle
      sagittal range of motion (ROM), patients' global satisfaction, local adverse
      events and consumption of rescue analgesics were analyzed. RESULTS: Seventy-five
      patients completed the study. Significant improvement in AOS and AOFAS
      ankle/hindfoot scores was noted at 1 week, 1 month, 3 months and 6 months post
      the fifth injection (P < 0.001 compared with baseline). The mean reduction of AOS
      score was 1.9, 2.6, 2.5 and 2.6 at each following visit (P < 0.001). The mean
      AOFAS ankle/hindfoot score improved from 64 points at baseline to 75, 78, 78, and
      78 points at 1 week, 1 month, 3 months and 6 months, respectively, post the fifth
      injection (P < 0.001). Ankle sagittal ROM did not improve significantly (P >
      0.05). The majority of patients reported satisfaction at 1 week (100%), 1 month
      (100%), 3 months (90.7%) and 6 months (86.7%) follow-up. Local adverse events
      occurred in 6.7% of patients. Acetaminophen consumption dropped significantly
      following treatment (P < 0.001). CONCLUSION: Five weekly intra-articular
      injections of Artz provide pain relief and functional improvements in patients
      with Kellgren-Lawrence grades I and II ankle OA. The clinical effect was rapid at
      1 week and may last for 6 months or more.

PMID- 16635583
TI  - Estimation of the identity of proteolytic aggrecan fragments using PAGE migration
      and Western immunoblot.
AB  - OBJECTIVE: To develop calculation models, using Western immunoblot, as a tool for
      the estimation of proteolytic human aggrecan fragment identity. METHOD: Seven
      human aggrecan fragments (calibrators), purified by CsCl gradient centrifugation
      and identified by Western immunoblot of N- and C-terminals, were used to develop
      calculation models. The models were used for identification of unknown aggrecan
      fragments each having one of their N- or C-terminals identified. RESULTS: The
      calibrator molecular weights (Mw) from sodium dodecyl sulfate (SDS)-gels (m), the
      Mw of amino acids (a) and the Mw of their carbohydrate substitution (g) were
      expressed as K = m/(a+g), or as K = 1.085m/(a+g) when compensation for the G1
      domain was required. Using these models together with average K-values, 12 out of
      the 17 immuno-detected aggrecan fragments were calculated to a known protease
      cleavage site, while five were identified to domain levels. CONCLUSIONS: With six
      neoepitope antibodies together with antibodies against the G1- and G3-domain it
      was possible to predict the identity of several proteolytic fragments from
      different regions within the aggrecan monomer.

PMID- 16635584
TI  - Determination of structural modification in acid activated montmorillonite clay
      by FT-IR spectroscopy.
AB  - The structural modifications and the Bronsted acid sites generated during the
      acid treatment of montmorillonite clay with varied concentration of sulphuric
      acid was determined using FT-IR spectroscopy. Octahedral sheet is affected at low
      acid concentration resulting into the dissolution of cations; among them Mg2+
      cations are prone to dissolve than Fe2+/3+ and Al3+. Tetrahedral sheet is
      affected at higher acid concentration. The partial substitution of octahedral
      Al3+ by Mg2+ or Fe2+/3+ cations and the presence of other non-smectite minerals
      such as kaolinites was also been clearly identified, thus making FT-IR
      spectroscopy as a rapid technique for monitoring the structural features of
      montmorillonite clay.

PMID- 16635585
TI  - Plasmodium rhoptries: how things went pear-shaped.
AB  - Plasmodium parasites have three sets of specialised secretory organelles at the
      apical end of their invasive forms--rhoptries, micronemes and dense granules. The
      contents of these organelles are responsible for or contribute to host cell
      invasion and modification, and at least four apical proteins are leading vaccine
      candidates. Given the unusual nature of Plasmodium invasion, it is not surprising
      that unique proteins are involved in this process. Nowhere is this more evident
      than in rhoptries. We have collated data from several recent studies to compile a
      rhoptry proteome. Discussion is focussed here on rhoptry content and function.

PMID- 16635586
TI  - A tale of three genomes: the kinetoplastids have arrived.
AB  - July 2005 marked a milestone in kinetoplastid biology research. A tour de force
      effort led by the Tri-Trypanosomatidae "Tritryp" genome consortium yielded the
      publication of three prominent kinetoplastid parasite genome sequences:
      Trypanosoma brucei, Trypanosoma cruzi and Leishmania major. The individual and
      combined comparative analyses of these three genome sequences, combined with
      proteomic analyses, have yielded insights into topics ranging from genome
      evolution and horizontal gene transfer to potential new therapeutic and vaccine
      targets.

PMID- 16635587
TI  - Antimicrobial peptides in the interactions between insects and flagellate
      parasites.
AB  - Innate immunity has a key role in the control of microbial infections in both
      vertebrates and invertebrates. In insects, including vectors that transmit
      parasites that cause major human and animal diseases, antimicrobial peptides
      (AMPs) are important components of innate immunity. AMPs are induced upon
      parasitic infections and can participate in regulating parasite development in
      the digestive tract and in the hemolymph. This review presents our current
      knowledge of a field that is in its infancy: the role of innate immunity in
      different models of insects infected with flagellate parasites, and in particular
      the potential role of AMPs in regulating these parasitic infections.

PMID- 16635588
TI  - Volatile biomarkers of pulmonary tuberculosis in the breath.
AB  - Pulmonary tuberculosis may alter volatile organic compounds (VOCs) in breath
      because Mycobacteria and oxidative stress resulting from Mycobacterial infection
      both generate distinctive VOCs. The objective of this study was to determine if
      breath VOCs contain biomarkers of active pulmonary tuberculosis. Head space VOCs
      from cultured Mycobacterium tuberculosis were captured on sorbent traps and
      assayed by gas chromatography/mass spectroscopy (GC/MS). One hundred and thirty
      different VOCs were consistently detected. The most abundant were naphthalene, 1
      methyl-, 3-heptanone, methylcyclododecane, heptane, 2,2,4,6,6-pentamethyl-,
      benzene, 1-methyl-4-(1-methylethyl)-, and cyclohexane, 1,4-dimethyl-. Breath VOCs
      were assayed by GC/MS in 42 patients hospitalized for suspicion of pulmonary
      tuberculosis and in 59 healthy controls. Sputum cultures were positive for
      Mycobacteria in 23/42 and negative in19/42 patients. Breath markers of oxidative
      stress were increased in all hospitalized patients (p<0.04). Pattern recognition
      analysis and fuzzy logic analysis of breath VOCs independently distinguished
      healthy controls from hospitalized patients with 100% sensitivity and 100%
      specificity. Fuzzy logic analysis identified patients with positive sputum
      cultures with 100% sensitivity and 100% specificity (95.7% sensitivity and 78.9%
      specificity on leave-one-out cross-validation); breath VOC markers were similar
      to those observed in vitro, including naphthalene, 1-methyl- and cyclohexane, 1,4
      dimethyl-. Pattern recognition analysis identified patients with positive sputum
      cultures with 82.6% sensitivity (19/23) and 100% specificity (18/18), employing
      12 principal components from 134 breath VOCs. We conclude that volatile
      biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the
      breath test distinguished between "sick versus well" i.e. between normal controls
      and patients hospitalized for suspicion of pulmonary tuberculosis, and between
      infected versus non-infected patients i.e. between those whose sputum cultures
      were positive or negative for Mycobacteria.

PMID- 16635589
TI  - Pathogenic human monoclonal antibody against desmoglein 3.
AB  - Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous disease
      associated with production of IgG autoantibodies to desmoglein 3 (Dsg3), a 130
      kDa epidermal cadherin protein. The binding of pathogenic antibody to Dsg3 on
      epidermal keratinocytes leads to loss of intercellular adhesion and results in
      intraepithelial blister formation. Here, we describe a human monoclonal antibody,
      PVMAB786, a Dsg3-specific IgG4 antibody, from an untreated patient with active
      PV. The antibody reacts with a 130-kDa protein on keratinocyte cell surfaces and
      recombinant Dsg3 protein, but not desmoglein 1 protein. PVMAB786 induces
      acantholysis in normal human skin and mucous membranes and induces a clinical and
      histological profile similar to human PV when injected into neonatal mice.
      PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial
      cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V
      gene and isotype usage in PV pathogenesis.

PMID- 16635590
TI  - Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops
      asper phospholipase A2 myotoxins in vivo and in vitro.
AB  - Previous studies have shown that calcineurin activity plays a critical role in
      the myotoxic activity induced by crotoxin (CTX), a group II phospholipase A(2)
      (PLA(2)) with neurotoxic and myotoxic actions. In order to address whether
      calcineurin is also important for the activity of non-neurotoxic group II PLA(2)
      myotoxins we have compared the effects of calcineurin inhibition on the myotoxic
      capacity of CTX and the non-neurotoxic PLA(2)s, myotoxin II (Mt II) and myotoxin
      III (Mt III) from Bothrops asper venom. Rats were treated with cyclosporin A
      (CsA) or FK506, calcineurin inhibitors, and received an intramuscular injection
      of either CTX, Mt II or Mt III into the tibialis anterior. Animals were killed 24
      h after injection of toxins. Tibialis anterior was removed and stored in liquid
      nitrogen. Myofibers in culture were also treated with CsA or FK506 and exposed to
      CTX, Mt II and Mt III. It was observed that, in contrast to CTX, CsA and FK506 do
      not attenuate myotoxic effects induced by both Mt II and Mt III in vivo and in
      vitro. The results of the present study suggest that calcineurin is not essential
      for the myotoxic activity of Mt II and Mt III, indicating that distinct
      intracellular pathways might be involved in myonecrosis induced by neurotoxic CTX
      and non-neurotoxic Bothrops sp. PLA(2) myotoxins. Alternatively, calcineurin
      dependent fast fiber type shift might render the muscle resistant to the action
      of CTX, without affecting its susceptibility to Bothrops sp. myotoxins.

PMID- 16635591
TI  - Phylogenetic diversity of Pasteurellaceae and horizontal gene transfer of
      leukotoxin in wild and domestic sheep.
AB  - Wild and domestic animal populations are known to be sources and reservoirs of
      emerging diseases. There is also a growing recognition that horizontal genetic
      transfer (HGT) plays an important role in bacterial pathogenesis. We used
      molecular phylogenetic methods to assess diversity and cross-transmission rates
      of Pasteurellaceae bacteria in populations of bighorn sheep, Dall's sheep,
      domestic sheep and domestic goats. Members of the Pasteurellaceae cause an array
      of deadly illnesses including bacterial pneumonia known as "pasteurellosis", a
      particularly devastating disease for bighorn sheep. A phylogenetic analysis of a
      combined dataset of two RNA genes (16S ribosomal RNA and RNAse P RNA) revealed
      remarkable evolutionary diversity among Pasteurella trehalosi and Mannheimia
      (Pasteurella) haemolytica bacteria isolated from sheep and goats. Several
      phylotypes appeared to associate with particular host species, though we found
      numerous instances of apparent cross-transmission among species and populations.
      Statistical analyses revealed that host species, geographic locale and biovariant
      classification, but not virulence, correlated strongly with Pasteurellaceae
      phylogeny. Sheep host species correlated with P. trehalosi isolates phylogeny
      (PTP test; P=0.002), but not with the phylogeny of M. haemolytica isolates,
      suggesting that P. trehalosi bacteria may be more host specific. With regards to
      populations within species, we also discovered a strong correlation between
      geographic locale and isolate phylogeny in the Rocky Mountain bighorn sheep (PTP
      test; P=0.001). We also investigated the potential for HGT of the leukotoxin A
      (lktA) gene, which produces a toxin that plays an integral role in causing
      disease. Comparative analysis of the combined RNA gene phylogeny and the lktA
      phylogenies revealed considerable incongruence between the phylogenies,
      suggestive of HGT. Furthermore, we found identical lktA alleles in unrelated
      bacterial species, some of which had been isolated from sheep in distantly
      removed populations. For example, lktA sequences from P. trehalosi isolated from
      remote Alaskan Dall's sheep were 100% identical over a 900-nucleotide stretch to
      sequences determined from M. haemolytica isolated from domestic sheep in the UK.
      This extremely high degree of sequence similarity of lktA sequences among
      distinct bacterial species suggests that HGT has played a role in the evolution
      of lktA in wild hosts.

PMID- 16635592
TI  - Non-pharmacological pain relief.
AB  - The delivery of humane neonatal care demands that attention is given to
      interventions that reduce pain effectively. Painful procedures are common for
      neonatal patients and a growing body of research suggests that simple non
      pharmacological methods are effective in reducing the signs of pain. Both oral
      sucrose and pacifiers reduce pain scores during procedures, and other simple
      measures, including facilitated tucking and skin-to-skin contact, might also be
      effective. Organising care to reduce exposure to painful procedures and also
      optimising the devices used for procedures might reduce the experience of pain.
      There is some evidence of long-term improvement in pain sensitivity following
      pain reduction programmes. Further research is needed to understand the detail of
      how and when to best apply these interventions; the long-term outcomes of
      policies that give routine prominence to pain reduction on the neonatal intensive
      care unit also need to be investigated. The absence of long-term effect should
      not impede the introduction of these simple, low-cost humane measures.

PMID- 16635593
TI  - Comparison of coronary risk factors and quality of life in coronary artery
      disease patients with versus without diabetes mellitus.
AB  - It is unclear whether patients with coronary artery disease (CAD) and diabetes
      mellitus (DM) can make comprehensive lifestyle changes that produce similar
      changes in coronary risk factors and quality of life compared with patients with
      CAD and without DM. We examined medical characteristics, lifestyle, and quality
      of life by diabetic status and gender in the Multicenter Lifestyle Demonstration
      Project (MLDP), a study of 440 nonsmoking patients with CAD (347 men, 55 with DM;
      15.9%; 93 women, 36 with DM; 38.7%). Patients met in groups to improve lifestyle
      (plant-based, low-fat diet; exercise; stress management) for 1 year. Follow-ups
      were conducted at 3 and 12 months. At baseline, body mass and systolic blood
      pressure were significantly higher among patients with DM. Men with DM had a
      worse medical history (e.g., hypertension, hyperlipidemia, and family history of
      CAD) than did those without DM. Patients with DM, especially women, reported
      poorer quality of life than did patients without DM. The 2 groups of patients
      were able to adhere to the recommended lifestyle, as demonstrated by significant
      improvements in weight (mean -5 kg), body fat, low-density lipoprotein
      cholesterol, exercise capacity, and quality of life. No significant changes in
      triglycerides and high-density lipoprotein cholesterol were noted. By the end of
      12 months, improvements in glucose-lowering medications (i.e., discontinuation or
      a change from insulin to oral hypoglycemic agents) were noted for 19.8% (n = 18)
      of patients with DM. In conclusion, patients with CAD and DM are able to follow a
      comprehensive lifestyle change program and show similar improvements in coronary
      risk factors and quality of life as those without DM.

PMID- 16635594
TI  - An insulin-like growth factor-I promoter polymorphism is associated with
      increased mortality in subjects with myocardial infarction in an elderly
      Caucasian population.
AB  - We investigated whether an insulin-like growth factor I (IGF-I) promoter
      polymorphism is associated with excess mortality in elderly subjects with
      myocardial infarction (MI). This association was assessed in 7,983 subjects of
      the Rotterdam Study during 14 years of follow-up. Among 345 subjects who
      developed a MI, the risk of mortality was 1.49 times higher in the variant
      carriers of the IGF-I promoter polymorphism than in the nonvariant carriers (95%
      confidence interval 1.10 to 2.10, p = 0.02). The risk of death increased with the
      number of variant alleles. Our study suggests that genetically determined low IGF
      I activity is an important determinant of mortality in subjects with MI.

PMID- 16635595
TI  - Relation between obesity and severity of coronary artery disease in patients
      undergoing coronary angiography.
AB  - We examined the relations among body mass index (BMI), extent of coronary artery
      disease, and frequency of high-risk coronary anatomy (HRCA) in 928 consecutive
      patients who underwent coronary angiography during a 6-month period. HRCA was
      defined as >or=50% stenosis of the left main coronary artery and/or significant 3
      vessel coronary artery disease (>or=70% narrowing). BMI was classified into 5
      subgroups: low (<21 kg/m(2)), normal (21 to 24 kg/m(2)), overweight (25 to 29
      kg/m(2)), obese (30 to 34 kg/m(2)), and severely obese (>or=35 kg/m(2)). Obese
      patients (BMI >or=30 kg/m(2)) were younger (61.4 +/- 10.7 vs 65.3 +/- 11.4 years,
      p <0.0001) and had higher prevalences of hyperlipidemia, systemic hypertension,
      and diabetes mellitus. HRCA was present less often in obese patients (56 of 245,
      23%, vs 250 of 683, 37%, p = 0.0002). Multivariate regression analysis showed
      that advancing age (p <0.0001), male gender (p = 0.007), diabetes mellitus (p =
      0.0004), and hyperlipidemia (p = 0.0008) were independent predictors of high-risk
      anatomy, whereas obesity remained a significant negative independent predictor (p
      = 0.02). Late (30 to 36 months) mortality was not different between obese (6.9%)
      and nonobese (8.2%) patients but was significantly higher in patients with HRCA
      (12.4%) than in those without HRCA (5.6%, p = 0.0003). In conclusion, obese
      patients who were referred for coronary angiography were younger and had a lower
      prevalence of HRCA. Obese patients were probably referred for angiography at an
      earlier stage of their disease, thus explaining the "obesity paradox" in several
      reports of better short-term outcome in obese patients who undergo cardiac
      procedures.

PMID- 16635596
TI  - Cardiovascular morbidity and mortality in community-dwelling elderly individuals
      with calcification of the fibrous skeleton of the base of the heart and
      aortosclerosis (The Cardiovascular Health Study).
AB  - In the elderly, mitral annular calcification (MAC) and aortic valve sclerosis
      (AVS) are associated with increased cardiovascular morbidity and mortality.
      Aortic annular calcification (AAC) commonly occurs with MAC. However, the
      prognostic value of AAC, singly or in combination with MAC and AVS, for incident
      cardiovascular disease and mortality is unknown. From the Cardiovascular Health
      Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60% women) who had
      an echocardiogram at the 1994 to 1995 examination and who were prospectively
      followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification
      categories were associated with incident congestive heart failure (MAC: hazard
      ratio [HR] 1.71, 95% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95% CI
      1.28 to 2.06, and AVS: HR 1.50, 95% CI 1.19 to 1.89) and death. A stronger
      association with incident cardiovascular disease and mortality was observed with
      a larger number of calcification categories and with increased MAC severity.
      Moreover, in the participants with prevalent cardiovascular disease at
      echocardiographic examination (n = 1,054), MAC and AAC were still associated with
      cardiovascular mortality (MAC: HR 1.91, 95% CI 1.04 to 3.50; AAC: HR 2.11, 95% CI
      1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are
      associated with a significant risk of incident congestive heart failure,
      cardiovascular and all-cause mortalities, and worse outcome in older patients
      with preexisting cardiovascular disease. Elderly patients with these findings
      represent a high-risk group and may require close medical attention.

PMID- 16635597
TI  - Relation of depressive mood to plasminogen activator inhibitor, tissue
      plasminogen activator, and fibrinogen levels in patients with versus without
      coronary heart disease.
AB  - The increased risk of coronary heart disease (CHD) associated with depression is
      well documented. We hypothesized that impaired fibrinolysis is involved in this
      link. To explore the association of depressive mood and/or vital exhaustion with
      various measurements of fibrinolysis activity, 231 men (40 to 65 years old; 123
      without CHD and taking no medication and 108 with documented CHD), completed the
      Center of Epidemiologic Studies Depression Scale and the Maastricht Questionnaire
      for vital exhaustion. Using classic cut-off points (Center of Epidemiologic
      Studies Depression Scale score >or=17, Maastricht Questionnaire score >or=8),
      6.5% and 9.8% of subjects without CHD and 38% and 48.1% of those with CHD were
      classified as depressed and exhausted, respectively. Patients with CHD were
      older, had a higher body mass index, and higher levels of total cholesterol,
      glucose, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator
      (t-PA) antigen, and fibrinogen; 47% were treated for hypertension. Depressed
      subjects had higher levels of PAI-1 activity (p = 0.006) and exhausted patients
      had higher levels of PAI-1 activity (p = 0.011) and fibrinogen (p = 0.009). After
      adjusting for clinical condition (with or without CHD), smoking, hypertension,
      triglyceride concentration, and body mass index, PAI-1 activity remained higher
      in depressed subjects (p = 0.03). This association persisted after further
      adjustment for vital exhaustion or for t-PA antigen and fibrinogen levels. t-PA
      antigen and fibrinogen levels were not associated with depressive mood in
      multivariate analyses. No fibrinolytic variable was associated with vital
      exhaustion in multivariate analyses. In conclusion, depressive mood, but not
      vital exhaustion, is associated with higher levels of PAI-1 activity, suggesting
      a possible impairment of fibrinolysis and indicating a potential additional
      mechanism by which depressive mood may act as a cardiovascular risk factor.

PMID- 16635598
TI  - An intravascular ultrasound analysis of the mechanisms of restenosis comparing
      drug-eluting stents with brachytherapy.
AB  - There are treatment failures after de novo drug-eluting stent (DES) implantation
      and after treatment with DESs or vascular brachytherapy (VBT) of in-stent
      restenosis (ISR) lesions. We studied 38 patients who presented with DES failure
      (26 patients after de novo DES implantation and 12 patients after DES treatment
      of ISR) and 30 patients who presented with VBT failure (all after treatment of
      ISR). Standard clinical data were collected and volumetric intravascular
      ultrasound was measured. Patients who presented with DES failures were 58.8 +/-
      9.6 years of age and those who presented with VBT failures were 59.8 +/- 8.7
      years of age; 60.5% of DES and 58.6% of VBT failures were in men; 31.5% of DES
      failures and 46.6% of VBT failures occurred in diabetic patients; and times to
      presentation were 210 +/- 101 days in DES failures and 510 +/- 527 days in VBT
      failures (p = 0.001). Minimal stent area was significantly larger in VBT than in
      the 2 DES failure groups (de novo DES implantation and DES treatment of ISR, p
      <0.0001); this was associated with more neointimal hyperplasia in VBT failures (p
      <0.0001). After it was normalized to stent length, intimal hyperplasia was
      diffusely distributed in VBT failures; conversely, DES failures were associated
      with less intimal hyperplasia and the intimal hyperplasia was mostly focal, with
      greater accumulation in the proximal and mid segments. In conclusion, VBT
      failures were caused by significant, recurrent, and diffuse intimal hyperplasia
      in the setting of adequate stent expansion, whereas DES failures were caused by
      only modest, but focal, intimal hyperplasia in the setting of DES underexpansion.

PMID- 16635599
TI  - Comparison of safety and efficacy of sirolimus-eluting stents versus bare metal
      stents in patients with ST-segment elevation myocardial infarction.
AB  - Sirolimus-eluting stents (SESs) are superior to bare metal stents (BMSs) for
      percutaneous coronary intervention, but data regarding SESs in ST-segment
      elevation myocardial infarction (STEMI) are limited. We investigated the clinical
      outcomes of patients with STEMI who were treated with SESs. We measured clinical
      characteristics and acute and long-term outcomes in 306 consecutive patients with
      STEMI who received a SES (n = 156) or a BMS (n = 150). Patients were followed for
      death, nonfatal reinfarction, and target vessel revascularization. Patients with
      SESs had a 0.6% in-hospital mortality rate versus 5.3% in patients with BMSs (p =
      0.015). Six-month mortality rates were 1.9% (SES) and 10.1% (BMS, p = 0.003). At
      6 months, patients with SESs were less likely to have target vessel
      revascularization (1.3% vs 8.1%, p = 0.005) and achieve the composite end point
      (3.2% vs 16.1%, p = 0.0001). No subacute thrombosis or clinical restenosis
      occurred in the SES group. Patients who received BMSs were older, received more
      stents, and had more myocardial damage, worse renal function, and lower ejection
      fractions than did those in the SES group. By multivariate discriminant analysis,
      stent type (SES vs BMS) was the most significant determinant of the 6-month
      composite end point (p = 0.01) and the need for target vessel revascularization
      (p = 0.02). In conclusion, SESs are safe and effective in STEMI at 6 months.

PMID- 16635600
TI  - Comparison of effectiveness and safety of drug-eluting stents versus vascular
      brachytherapy for saphenous vein graft in-stent restenosis.
AB  - We investigated the safety and efficacy of drug-eluting stents (DESs) for the
      treatment of patients who presented with in-stent restenosis (ISR) of saphenous
      vein grafts (SVGs) and compared the in-hospital and 6-month clinical outcomes of
      DESs with those of intravascular brachytherapy and balloon angioplasty alone.
      Records of 187 patients who presented with ISR of SVGs were analyzed. Of these,
      34 consecutive patients were treated with DES implantation, 93 were treated with
      intravascular brachytherapy (n = 60 with gamma-radiation, n = 33 with beta
      radiation), and 60 patients underwent conventional treatment with balloon
      angioplasty alone. Clinical and angiographic characteristics at baseline were
      comparable between groups. The DES group had less non-Q-wave myocardial
      infarction than did the intravascular brachytherapy and balloon angioplasty
      groups (0%, 20%, and 26%, p = 0.003 and <0.001, respectively). At 6 months, death
      occurred in 0% of the DES group, 2% of the intravascular brachytherapy group, and
      5% of the balloon angioplasty group (p = 0.36 and <0.18, respectively). Target
      lesion revascularization/major adverse cardiac events were similar in the
      intravascular brachytherapy and DES groups (12% and 3%, p = 0.13) and
      significantly decreased compared with patients who were treated with balloon
      angioplasty alone (55%, p <0.001 for the 2 comparisons). The results of this
      retrospective analysis suggest that DES implantation is at least as effective and
      safe as intravascular brachytherapy for the treatment of SVG ISR and that these
      treatment modalities are superior to balloon angioplasty alone.

PMID- 16635601
TI  - Primary and rescue percutaneous coronary intervention with paclitaxel-eluting
      stent implantation in ST-elevation myocardial infarction.
AB  - We conducted a retrospective comparison of paclitaxel-eluting stents (PESs, n =
      60) versus bare metal stents (BMSs, n = 137) in consecutive patients who
      underwent primary or rescue percutaneous coronary intervention over 1 year. The
      PES cohort had no in-stent thromboses and had a 65% (p = 0.02) decrease in the
      combined end point of death, recurrent myocardial infarction, and target vessel
      revascularization at 1 year compared with the BMS group. PES implantation appears
      to be safe and possibly superior to BMS implantation in terms of 1-year major
      cardiovascular outcomes in the setting of ST-elevation myocardial infarction.

PMID- 16635602
TI  - C-Reactive protein, clinical outcome, and restenosis rates after implantation of
      different drug-eluting stents.
AB  - Sirolimus-eluting stents (SESs), paclitaxel-eluting stents (PESs), and
      dexamethasone-eluting stents (DEXs) have anti-inflammatory properties; thus, the
      decreased in-segment restenosis rate observed with the use of these stents might
      be related to a weaker postprocedural inflammatory response. One hundred sixty
      consecutive patients with stable coronary artery disease who underwent successful
      single-vessel/lesion coronary artery stenting were prospectively studied. Thin
      strut bare metal stents were deployed in 39 patients, SESs in 30, PESs in 61, and
      DEXs in 30. The 4 groups were similar with respect to demographic and
      angiographic variables and prevalence of risk factors. C-reactive protein (CRP)
      was measured at baseline and 24 and 48 hours after the procedure. Maximal
      increase in CRP was calculated as the increase in CRP at 48 hours/CRP compared
      with baseline. Angiographic follow-up was performed after 12.9 +/- 1.3 months or
      sooner, if needed, on the basis of clinical evidence. All patients presented a
      postprocedural increase in CRP that peaked at 48 hours (median 10.0 mg/L).
      Maximal CRP increase was similar across the 4 groups (medians 3.5 mg/L in the
      bare metal stent group, 3.6 mg/L in the SES group, 4.0 mg/L in the PES group, 3.5
      mg/L in the DEX group, p = 0.45). Incidences of angiographic binary restenosis
      (>50% lumen diameter decrease) were 20.5% in the bare metal stent group, 3.3% in
      the SES group, 4.9% in the PES group, and 36.6% in the DEX group (p = 0.0004 for
      SES and PES groups vs bare metal stent and DEX groups). Postprocedural increase
      in CRP was significantly correlated with clinical and angiographic outcomes. In
      conclusion, the acute postprocedural systemic inflammatory response induced by
      drug-eluting stent implantation appears to be similar to that induced by bare
      metal stents. However, the restenosis rate is lower for SESs and PESs than for
      DEXs and bare metal stents. Thus, the decreased incidence of stent restenosis
      that was observed after SES and PES deployment is unlikely to be related to a
      decreased acute systemic inflammatory response, but rather to an increased local
      resistance to inflammatory mediators.

PMID- 16635603
TI  - A prospective registry to evaluate sirolimus-eluting stents implanted at coronary
      bifurcation lesions using the "crush technique".
AB  - The "crush technique" has been proposed as an alternative approach to treat
      bifurcation lesions because of its predictability and high procedural success
      rate. However, few data are available regarding its safety and long-term
      efficacy. We report the long-term clinical outcomes of patients with coronary
      bifurcation lesions treated with sirolimus-eluting stents using the crush
      technique. From April 2003 to May 2004, 120 patients with coronary bifurcation
      lesions were treated with sirolimus-eluting stents using the crush technique. Six
      months of clinical follow-up was completed in 95.8% of patients. Mean patient age
      was 64 years; 36% had diabetes mellitus, and the left anterior descending
      artery/diagonal was the most frequent bifurcation location (69%). Final kissing
      balloon inflation was performed in 87.5% of patients. Compared with the main
      vessel, side branch lesions were shorter, with a smaller reference diameter and
      final in-stent minimum lumen diameter. Procedural success was achieved in 97.5%.
      At 30 days of follow-up, 1 patient had died of noncardiac causes and 2 patients
      (1.7%) had subacute stent thrombosis. At 6 months of follow-up, target lesion
      revascularization was required in 13 patients (11.3%), all of whom had focal
      restenosis predominantly at the side branch ostium. In conclusion, the crush
      technique with final kissing balloon inflation can be safely used by experienced
      operators to treat highly complex bifurcation lesions with sirolimus-eluting
      stents. The safety profile of this technique is similar to that of other
      bifurcation stenting techniques reported thus far. Nonetheless, despite the
      excellent patency rates of the main vessel, the need for revascularization at the
      ostium of the side branch was not fully eliminated.

PMID- 16635604
TI  - Location of focal vasospasm provoked by ergonovine maleate within coronary
      arteries in patients with vasospastic angina pectoris.
AB  - This study examined whether coronary focal vasospasm occurs in a nonuniform
      distribution within the coronary tree and whether a longitudinal plaque
      distribution pattern is present in patients with vasospastic angina using 3
      dimensional intravascular ultrasound analysis. Of 121 patients with clinically
      suspected angina without fixed stenosis in the coronary arteries, vasospasm was
      provoked in 82 patients with 92 lesions (42 focal, 50 diffuse) by intravenous
      ergonovine maleate injection. Most focal vasospasms occurred in the proximal
      third of the coronary arteries (proximal 28, mid 8, distal 6, p <0.01),
      corresponding to the historical high-risk zones for acute coronary occlusion.
      More plaque burden also existed in the proximal third of the coronary arteries in
      patients with focal vasospasm.

PMID- 16635605
TI  - Usefulness of intramyocardial injection of autologous bone marrow-derived
      mononuclear cells in patients with severe angina pectoris and stress-induced
      myocardial ischemia.
AB  - Bone marrow cell transplantation has been proposed as a novel therapeutic option
      for patients with coronary artery disease. This study investigated whether
      autologous bone marrow-derived mononuclear cell injection into the ischemic
      myocardium of patients with severe angina pectoris could safely reduce anginal
      symptoms, improve myocardial perfusion, and increase left ventricular (LV)
      function. In a total of 20 patients (63 +/- 10 years old; 16 men) with angina
      pectoris, myocardial segments with stress-induced ischemia as assessed by gated
      single-photon emission computed tomography were injected with 30 to 100 million
      mononuclear cells. Anginal symptoms, Canadian Cardiovascular Society class, and
      quality of life were assessed at 3 and 6 months of follow-up. At baseline and 3
      months of follow-up, an exercise test, gated single-photon emission computed
      tomography, and magnetic resonance imaging were performed to assess exercise
      capacity, myocardial perfusion, and LV function. Intramyocardial injection of
      autologous bone marrow-derived mononuclear cells was safe. The Canadian
      Cardiovascular Society class improved from 3.5 +/- 0.5 at baseline to 2.4 +/- 0.6
      after 3 months (p <0.01) and 2.4 +/- 0.6 after 6 months (p <0.01). The quality-of
      life score improved from 52 +/- 10% to 71 +/- 10% at 3 months (p <0.01) to 73 +/-
      15% at 6 months (p <0.01). The exercise capacity increased from 79 +/- 31% to 84
      +/- 29% (p <0.05). Magnetic resonance imaging revealed an increased LV ejection
      fraction from 51 +/- 11% to 54 +/- 10% (p <0.01) and a reduced LV end-systolic
      volume from 97 +/- 50 to 88 +/- 42 ml (p <0.01). The wall motion score index
      improved from 0.36 +/- 0.32 to 0.24 +/- 0.28 (p <0.01). The number of segments
      with stress-induced ischemia decreased from 5.1 +/- 3.2 to 2.3 +/- 2.6 (p<0.01).
      In conclusion, autologous bone marrow-derived mononuclear cell injection in
      patients with ischemia is safe, reduces anginal symptoms, improves myocardial
      perfusion, and increases LV function.

PMID- 16635606
TI  - Effect of statins on platelet PAR-1 thrombin receptor in patients with the
      metabolic syndrome (from the PAR-1 inhibition by statins [PARIS] study).
AB  - We investigated whether, in primary prevention patients with metabolic syndrome,
      statins affect the platelet protease-activated receptor-1 (PAR-1) thrombin
      receptor by performing serial measurements of its activity and the antigen
      expression level by flow cytometry before and during treatment. Recent data from
      randomized trials of statins are compatible with the possibility of clinically
      relevant pleiotropic effects. The use of statins is associated with a reduced
      thrombosis burden and diminished platelet activity, as shown in animal models and
      in vitro studies. Seventy patients with the metabolic syndrome who were not
      taking antiplatelet agents were assigned consecutively at starting doses at the
      discretion of the responsible clinician to 1 of 6 statins (atorvastatin,
      fluvastatin, lovastatin, pravastatin, rosuvastatin, or simvastatin) or to a no
      statin group for 6 weeks. Platelet expression of intact (SPAN12 antibody) and
      cleaved (WEDE15) PAR-1 thrombin receptors were assessed by flow cytometry at
      baseline and at weeks 4 and 6 of treatment. At baseline, no difference was found
      in receptor expression. However, after 4 weeks of treatment, all statins had
      significantly inhibited (46% to 55%) the activated epitope of PAR-1 expression.
      After 6 weeks, inhibition remained, despite a slight rebound (22% to 37%). Also,
      a delayed pattern of inhibition of the intact PAR-1 receptor epitope was found.
      In conclusion, all statins inhibited the activity and antigen level of the
      platelet PAR-1 thrombin receptor, which has a major role in regulating platelet
      activity and thrombin formation. These observational data offer a plausible
      mechanism for the recently demonstrated pleiotropic effects of statins that may
      contribute to early clinical benefit.

PMID- 16635607
TI  - Association of lipoprotein lipase Hind III and Ser 447 Ter polymorphisms with
      dyslipidemia in Asian Indians.
AB  - Studies have shown an association between the lipoprotein lipase gene and
      dyslipidemia and atherosclerosis in some populations. The aim of this study was
      to investigate the association between the common lipoprotein lipase HindIII (T
      G) and Ser447Ter (C-G) polymorphisms with dyslipidemia in Asian Indians, who are
      known to have very high rates of premature coronary artery disease. A total of
      1,015 subjects, comprising 550 normal glucose-tolerant subjects and 465 patients
      with type 2 diabetes, were randomly selected from the Chennai Urban Rural
      Epidemiology Study. The total serum cholesterol, high-density lipoprotein (HDL)
      cholesterol, and serum triglyceride levels were assayed using enzymatic methods.
      Low-density lipoprotein cholesterol was calculated using the Friedewald formula.
      Genotyping was done using the polymerase chain reaction-restriction fragment
      length polymorphism method. A significant association was found between the H+
      allele of HindIII with low HDL cholesterol and elevated triglyceride levels. The
      Ser allele of Ser447Ter was also strongly associated with low HDL cholesterol
      levels. No association was found between the H+ allele and Ser Allele with the
      total or low-density lipoprotein cholesterol levels. Group-wise haplotype
      frequencies were generated using the expectation-maximization algorithm to detect
      differences in overall haplotype frequency profiles between the case-control
      groups. The haplotype analysis showed that the H+ Ser and H- Ter were the "high
      risk" and "low-risk" haplotypes for low HDL cholesterol and elevated triglyceride
      levels, respectively. In conclusion, the H+ Ser haplotype of the lipoprotein
      lipase gene was associated with low HDL cholesterol levels and
      hypertriglyceridemia in Asian Indians.

PMID- 16635608
TI  - Is time to first recurrence of atrial fibrillation correlated with atrial
      fibrillation burden?
AB  - The time to the first recurrence of atrial fibrillation (AF) and the AF burden
      have commonly been used as end points for AF therapy. We conducted a
      retrospective analysis of data from a large pacemaker registry to assess the
      relation between the time to the first recurrence and the AF burden. Although a
      statistical association exists, the small correlation coefficients limit the
      clinical value of the time to first recurrence as an indicator of AF burden.

PMID- 16635609
TI  - C-Reactive protein in lone atrial fibrillation.
AB  - An inflammatory cause of atrial fibrillation (AF) has been proposed on the basis
      of the presence of lymphocytic infiltrates in the biopsy results of patients with
      lone AF, alterations of C-reactive protein (CRP) and interleukin-6 levels in
      subjects with AF, and the time course of postoperative AF. Many previous studies
      exploring inflammatory factors in AF have been confounded by concomitant medical
      illnesses. Subjects with lone AF provide a unique opportunity to eliminate the
      effects of associated conditions. We therefore sought to determine CRP levels in
      homogenous cohorts of patients with lone AF or AF and hypertension. One hundred
      twenty-one subjects with lone AF, 52 subjects with AF and hypertension, and 75
      control subjects were enrolled and studied. Plasma CRP levels were determined
      using a commercially available immunoassay. There was no significant difference
      in CRP levels between subjects with lone AF and controls (1.34 vs 1.21 mg/L, p =
      0.18). CRP levels in subjects with AF and hypertension were elevated compared
      with those of controls and those of subjects with lone AF, although this
      difference was attributable to increased body mass indexes. CRP levels were not
      elevated in subjects with lone AF compared with controls. In conclusion, these
      findings clarify previous observations of elevations in CRP levels in subjects
      with AF and suggest that this marker of systemic inflammation is associated not
      with the arrhythmia per se, but rather with underlying cardiovascular disease.

PMID- 16635610
TI  - Ventricular arrhythmias and risk of death and acute myocardial infarction in
      apparently healthy subjects of age >or=55 years.
AB  - Increased ventricular ectopic activity and even more complex arrhythmias are not
      uncommon in subjects without apparent heart disease. However, their prognostic
      significance has been controversial and not updated in recent years. The
      prevalence and prognostic significance of different ventricular arrhythmias were
      studied in a cohort of middle-aged and elderly subjects without apparent heart
      disease. Six hundred seventy-eight men and women aged 55 to 75 years without a
      history of heart disease or stroke were included. Baseline examinations included
      physical examinations, fasting laboratory testing, and 48-hour ambulatory
      electrocardiographic monitoring. All patients were followed for up to 5 years.
      Combined events were defined as all-cause mortality or acute myocardial
      infarction. A cardiovascular event was defined as cardiovascular death or acute
      myocardial infarction. In total, 84% had 0 to 10 ventricular premature complexes
      (VPCs)/hour, 8% had 11 to 30 VPCs/hour, and 8% had >30 VPCs/hour; 10.8% had >or=1
      run of >or=3 VPCs. Frequent VPCs (>or=30/hour) was a significant predictor of
      combined (hazard ratio 2.47, 95% confidence interval 1.29 to 4.68, p = 0.006) and
      cardiovascular (hazard ratio 2.85, 95% confidence interval 1.16 to 7.0, p =
      0.023) event rates, after adjustment for conventional risk factors. Runs of >or=4
      VPCs/day or >or=2 doublets/day were also associated with a poor prognosis, but
      only in the presence of frequent VPCs. The detection of a single VPC on standard
      electrocardiography was a significant predictor of frequent VPCs and an
      independent predictor of events (hazard ratio 2.6, 95% confidence interval 1.02
      to 6.66, p = 0.045). In conclusion, apparently healthy, middle-aged and elderly
      subjects with frequent VPCs (>or=30/hour) have a poor prognosis. According to
      current guidelines, strict risk-factor modification and primary prevention are
      justified in these high-risk subjects.

PMID- 16635611
TI  - Mechanism of cardiac output gain from cardiac resynchronization therapy in
      patients with coronary artery disease or idiopathic dilated cardiomyopathy.
AB  - The mechanisms underlying cardiac resynchronization therapy have consistently
      been studied at rest and remain ill defined. Peak stress total isovolumic time (t
      IVT) is a major determinant of cardiac output (CO) in chronic heart failure. In
      this study, pharmacologic stress was used to assess the effects of
      atrioventricular (AV) delay shortening and ventricular resynchronization elements
      of cardiac resynchronization therapy. Thirty patients undergoing cardiac
      resynchronization therapy were studied <6 months after implantation. t-IVT and CO
      were measured during native activation (left bundle branch block), AV delay
      shortening (right ventricular dual-chamber pacing), and full resynchronization
      (atrio-biventricular pacing). Full resynchronization shortened peak stress t-IVT
      by 9.4 +/- 6.2 s/min (p <0.001) and increased peak stress CO by 0.9 +/- 0.4 L/min
      (p <0.001), with the effects in individual patients showing a large correlation
      (r = -0.64, p <0.001). In contrast, simple AV delay shortening did not shorten
      peak stress t-IVT nor increase peak stress CO, nor was CO at rest affected by
      full resynchronization or AV delay shortening. Of all measurements during native
      activation, the best predictor of gain in peak stress CO from full
      resynchronization was peak stress t-IVT (r = 0.75, p <0.001), with every 5 s/min
      increment in peak stress t-IVT during native activation predicting a 6% gain in
      peak stress CO. No conventional measures during native activation at rest or
      during stress (including QRS duration, the Tei index, tissue Doppler
      intraventricular delay, and t-IVT at rest) added significant additional
      information. In conclusion, only during stress does resynchronization
      consistently increase CO. Second, little of this increment in CO is achieved by
      AV delay shortening alone. Third, under native activation, long t-IVT during peak
      stress is the single best predictor of resynchronization-mediated increment in
      peak stress CO.

PMID- 16635612
TI  - Factors associated with decreased cerebral blood flow in congestive heart failure
      secondary to idiopathic dilated cardiomyopathy.
AB  - Cerebral blood flow (CBF) is decreased and cognitive dysfunction develops in the
      advanced stages of heart failure. However, few data are available regarding the
      factors associated with decreased CBF. Fifty-two patients with advanced
      congestive heart failure (CHF) secondary to idiopathic dilated cardiomyopathy
      (ejection fraction <or=35%) and 10 healthy volunteers were included in this
      study. Echocardiography and symptom-limited bicycle exercise testing were
      performed. Global CBF was measured by radionuclide angiography. Global CBF was
      19% less in patients with CHF than in controls (p <0.01). Such reduced CBF became
      normalized in 4 patients with CHF who underwent cardiac transplantation. In a
      univariate linear regression analysis, global CBF was significantly associated
      with New York Heart Association functional class, disease duration, atrial
      fibrillation, serum B-type natriuretic peptide level, the early mitral
      velocity/early diastolic annular velocity ratio, and pulmonary artery systolic
      pressure. Global CBF was not found to be associated with the ejection fraction,
      peak oxygen consumption, or anaerobic threshold. In a stepwise multivariate
      linear regression analysis, serum B-type natriuretic peptide level (p = 0.047)
      and New York Heart Association functional class (p = 0.003) were significantly
      related to global CBF (global CBF = 48.373 - 0.05 x serum B-type natriuretic
      peptide level - 3.283 x New York Heart Association functional class; r(2) =
      0.401). In conclusion, CBF is decreased in patients with CHF, which may be used
      to predict disease severity and chronicity.

PMID- 16635613
TI  - Safety and tolerability of serial home infusions of nesiritide for advanced heart
      failure.
AB  - Although the therapeutic strategy of serial 6-hour intravenous infusions of
      nesiritide for advanced chronic heart failure (HF) is currently under
      investigation, frequent hospital or clinic visits may present logistical
      challenges for many patients with HF. Therefore, a pilot study was conducted to
      evaluate the safety and tolerability of serial nesiritide infusions administered
      at home in this patient population. Twenty patients with advanced HF were
      enrolled into a protocol for the administration of 12 weekly intravenous
      infusions of nesiritide (2 microg/kg bolus, 0.01 microg/kg/min for 6 hours) at
      home. Blood samples and weights were obtained weekly, and clinical assessments
      were made at 4 and 12 weeks. During the 12-week study period, there were 3 deaths
      unrelated to nesiritide therapy. Six patients required >or=1 hospitalization for
      HF. Two of 204 infusions resulted in symptomatic hypotension, and there were no
      adverse renal events. Mean body weight decreased at week 4 but returned to
      baseline by week 12. Antibodies to nesiritide were not detected in any patient.
      In conclusion, serial home infusions of nesiritide in patients with advanced HF
      appear to be safe and well tolerated, but the efficacy of this therapeutic
      strategy requires definition in a larger, randomized trial.

PMID- 16635614
TI  - Use of breath carbon monoxide to measure the influence of prosthetic heart valves
      on erythrocyte survival.
AB  - First-generation prosthetic heart valves commonly caused sufficient red blood
      cell (RBC) injury to induce hemolytic anemia. Although multiple studies have
      shown that new-generation valves are not associated with anemia, the extent to
      which these valves are injurious to RBCs is not known, because RBC survival not
      has not been measured in these subjects. Using a technique that uses breath
      carbon monoxide (CO) to quantify RBC turnover, this study measured RBC life span
      in 38 subjects with normally functioning, new-generation valves. Erythrocyte
      survival averaged 98.8 +/- 23 and 103 +/- 15 days, respectively, in 20 subjects
      with mechanical valves and 18 subjects with bioprosthetic valves (p >0.05).
      However, these life spans were significantly (p <0.01) less than those of healthy
      subjects (122 +/- 23 days) and a group of elderly subjects with osteoarthritis
      (128 +/- 26 days). The mean hemoglobin concentrations of the 2 groups of valve
      patients were within normal limits. In conclusion, new-generation heart valves
      commonly are associated with a small degree of hemolysis that is compensated for
      by increased RBC production.

PMID- 16635615
TI  - Elevated brain natriuretic peptide and reduced exercise capacity in adult
      patients operated on for tetralogy of fallot is due to biventricular dysfunction
      as determined by the myocardial performance index.
AB  - Although tetralogy of Fallot (TOF) can be repaired surgically, residual lesions
      that cause abnormal ventricular load can eventually lead to heart failure.
      Subclinical biventricular dysfunction in these patients may be detected only by
      using suitably sensitive indexes. The Tei index determined by the pulsed Doppler
      method enables the measurement of left ventricular (LV) and right ventricular
      (RV) function. This study was designed to evaluate the biventricular Tei indexes
      in adults with operated congenital heart disease and to correlate these indexes
      with cardiopulmonary capacity and neurohormonal activation. Fifty-nine patients
      with surgically corrected TOF and 52 patients with operated left-to-right-shunt
      defects were included in the study. Patients with TOF showed significantly
      greater LV and RV Tei indexes than those with left-to-right-shunt defects (LV Tei
      index 0.50 +/- 0.09 vs 0.34 +/- 0.05, RV Tei index 0.37 +/- 0.1 vs 0.25 +/- 0.06;
      p <0.0001). Peak oxygen uptake was significantly reduced in the patients with TOF
      (25 +/- 6 vs 32 +/- 6 ml x kg(-1) x min(-1), p <0.0001) and was correlated
      inversely with the LV Tei index (r = -0.61, p <0.0001). N-terminal-pro-brain
      natriuretic peptide was significantly increased in patients with TOF (150 +/- 141
      vs 57 +/- 39 pg/ml, p <0.0001). In conclusion, in asymptomatic or minimally
      symptomatic patients with TOF, biventricular dysfunction is detected by the Tei
      index. Further indexes for heart failure in these patients are increased
      circulating plasma N-terminal-pro-brain natriuretic peptide and impaired peak
      oxygen uptake. The combined determinations of these 3 variables enable the
      identification of congenital heart disease with impaired cardiac function before
      they become clinically symptomatic.

PMID- 16635616
TI  - Effects of statins on renal function after aortic cross clamping during major
      vascular surgery.
AB  - Ischemic reperfusion injury is an important cause of renal dysfunction after
      major vascular surgery and increases postoperative morbidity and mortality. The
      aim of the present study was to assess the effect of statins on renal function in
      patients at high risk for renal dysfunction, that is, those who underwent
      suprarenal aortic cross clamping-declamping. Seventy-seven patients (28 statin
      users, 57 men; mean age 69 +/- 8 years) with normal preoperative renal function
      requiring suprarenal aortic cross clamping-declamping during vascular surgery
      from 1995 to 2005 were studied. Creatinine levels were obtained before surgery
      and on days 1, 2, 3, 7, and 30 after surgery. An analysis-of-variance model for
      repeated measurements was applied to compare creatinine levels between statin
      users and nonusers, with adjustment for clamping time and blood loss. There were
      no differences in baseline clinical characteristics, preoperative creatinine
      levels (0.93 vs 0.96 mg/dl, p = 0.59), and glomerular filtration rate (79 vs 73
      ml/min, p = 0.1). Postoperative creatinine levels during the 30 days after
      surgery were significantly lower in statin users than in nonusers (analysis-of
      variance p <0.01, 1.17 vs 1.98 mg/dl). Postoperative hemodialysis was required
      (temporarily) in 7 patients (9.1%), all statin nonusers. These findings suggest
      an association between statin use and preserved renal function after suprarenal
      aortic clamping.

PMID- 16635617
TI  - Usefulness of bedside testing for brain natriuretic peptide to identify right
      ventricular dysfunction and outcome in normotensive patients with acute pulmonary
      embolism.
AB  - Echocardiographic right ventricular (RV) dysfunction is a well-established
      prognostic indicator in patients with acute pulmonary embolism. However, the
      possibility of implementing a rapid and effective triage with biohumoral markers
      such as brain natriuretic peptide (BNP) may be of value. Sixty-one patients with
      a first documented episode of acute pulmonary embolism without shock and previous
      left ventricular dysfunction were prospectively studied. All patients underwent
      echocardiography and rapid BNP testing on admission. Patients were followed up
      for in-hospital death, progression to shock, and nonfatal pulmonary embolism
      recurrence. Overall, 35 patients (57%) had echocardiographic evidence of RV
      dysfunction on admission, and its prevalence increased progressively with
      increasing levels of BNP. A BNP level <85 pg/ml was highly accurate in excluding
      RV dysfunction. No patient in the lower tertile of BNP values (1.1 to 85.0 pg/ml)
      had RV dysfunction, compared with 75% in the middle tertile (88.7 to 487.0 pg/ml)
      and 100% in the upper tertile (527 to 1,300 pg/ml). Overall, 11 patients (18%),
      belonging to the upper tertile, progressed to shock during admission, 4 of whom
      died. The association of RV dysfunction with a BNP level in the upper tertile
      (>or=527 pg/ml) showed incremental prognostic value over RV dysfunction alone (in
      hospital death and progression to shock were 55% and 31%, respectively). In the
      present study, BNP represented a powerful predictor of in-hospital clinical
      deterioration, with substantial incremental prognostic value over
      echocardiography alone.

PMID- 16635618
TI  - Intra-aortic balloon counterpulsation.
AB  - Intra-aortic balloon counterpulsation (IABP) is sometimes used in critically ill
      patients with cardiac disease. By increasing diastolic arterial pressure and
      decreasing systolic pressure, it reduces left ventricular afterload. IABP may be
      beneficial in subjects with cardiogenic shock, mechanical complications of
      myocardial infarction, intractable ventricular arrhythmias, or advanced heart
      failure or those who undergo "high-risk" surgical or percutaneous
      revascularization, but the evidence to support its use in these patient groups is
      largely observational. Contraindications to IABP include severe peripheral
      vascular disease as well as aortic regurgitation, dissection, or aneurysm. The
      potential benefits of IABP must be weighed against its possible complications
      (bleeding, systemic thromboembolism, limb ischemia, and, rarely, death).

PMID- 16635619
TI  - Donald Carey Harrison, MD: a conversation with the editor. Interview by William
      Clifford Roberts, MD.

PMID- 16635620
TI  - Decreased aortic root distensibility rather than increased aortic root diameter
      as an important cardiovascular risk factor in the Marfan syndrome.

PMID- 16635621
TI  - Evaluation of selected laboratory components of a comprehensive periodic health
      evaluation for veterans with spinal cord injury and disorders.
AB  - OBJECTIVE: To evaluate selected laboratory components of a comprehensive periodic
      health evaluation program for patients with spinal cord injury and disorders
      (SCI/D). DESIGN: A retrospective study. SETTING: A Department of Veterans Affairs
      spinal cord injury center. PARTICIPANTS: Community-dwelling male veterans with
      SCI/D (N=350). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Proportion
      of laboratory tests that resulted in new diagnoses (diagnostic yield) and
      proportion of laboratory tests that resulted in changes in management
      (therapeutic yield). RESULTS: Although abnormality rates for many routine
      laboratory tests were high (up to 31.5%), diagnostic and therapeutic yields were
      low (<1.5%), with the exception of glucose (therapeutic yield, 3.4%) and lipid
      tests (up to a 4.1% diagnostic and 15.2% therapeutic yield). CONCLUSIONS: Our
      data revealed that diagnostic and therapeutic yields for many laboratory
      components of the annual PHE program for veterans with SCI/D were low, consistent
      with findings in the general ambulatory population. Further data collection,
      particularly prospective longitudinal data, may help optimize the selection and
      frequency of laboratory tests performed as part of this program.

PMID- 16635622
TI  - A longitudinal study of health-related quality of life after traumatic brain
      injury.
AB  - OBJECTIVE: To examine the longitudinal course of health-related quality of life
      from 1 month to 3 to 5 years after traumatic brain injury (TBI). DESIGN:
      Longitudinal cohort study with 4 evaluation points. SETTING: Level I trauma
      center. PARTICIPANTS: Consecutive hospital admissions of 133 adolescents and
      adults with complicated mild to severe TBI who completed the outcome measure at
      all 4 time points, 111 general trauma patients, and 87 healthy friend controls.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Sickness Impact Profile.
      RESULTS: TBI patients reported significant limitations at 1 month postinjury,
      with substantial improvement occurring by 6 months, especially in the physical
      domain. Psychosocial improvement was smaller, and perceived cognitive, emotional,
      and communication difficulties did not change over the time period assessed.
      Persons with TBI had clear difficulties relative to healthy peers, but their
      reported level of difficulties was very similar to that of the persons who had
      sustained a general trauma by 1 year postinjury. CONCLUSIONS: In this sample, TBI
      was associated with significant early limitations in most aspects of everyday
      life. Considerable improvement was noted over the first 6 months postinjury,
      especially in physical domains. Some aspects of psychosocial functioning also
      improved, although reported limitations in communication, cognitive, and
      emotional domains remained constant over time. These findings highlight the
      persistence of injury-related difficulties that compromise quality of life.

PMID- 16635623
TI  - Effects of a postoperative strength-training program on the walking ability of
      children with cerebral palsy: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of a postoperative strength-training program
      on the walking of children with cerebral palsy (CP). DESIGN: Randomized
      controlled trial. SETTING: Hospital rehabilitation department. PARTICIPANTS:
      Thirty-nine children with CP (age range, 6-16 y). After orthopedic surgery, the
      control group (n=20) followed a conventional physiotherapy (PT) program, and the
      strength-training group (n=19) followed a strength-training program in addition
      to the conventional PT. Twenty-nine age-matched healthy children were used as
      references. INTERVENTION: A 9-month strength-training program. MAIN OUTCOME
      MEASURES: Spatiotemporal, kinematic, and kinetic parameters during gait analysis
      were analyzed before (E0) and 1 year after (E1) the surgery. For 22 children, a 2
      year postoperative gait analysis (E2) took place as well. RESULTS: At E1, several
      kinematic and kinetic parameters improved, although there was no significant
      difference between the groups. Spatiotemporal parameters showed a worsening at E1
      and a recovery to preoperative values at E2. CONCLUSIONS: The examined parameters
      may be more substantially influenced by factors such as the surgery outcome and
      the variability of pathologic characteristics than by the strength-training
      program per se. However, a more significant effect of the strength-training may
      appear if more intense and short-term training protocols are used, considering
      factors such as patients' motivations, ages, and postoperative statuses.

PMID- 16635624
TI  - Hand function and motor cortical output poststroke: are they related?
AB  - OBJECTIVES: To characterize hand function and cortical excitability in chronic
      and subacute stages of stroke recovery and to describe the relations between
      these measures. DESIGN: Observational, case-control, and cohort pre-post
      inpatient rehabilitation. SETTING: Motor performance laboratory. PARTICIPANTS:
      Fourteen community-living chronic and 14 subacute inpatient stroke survivors
      volunteered. Fourteen similarly aged healthy subjects served as a control group.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Finger tapping, peg
      placing, and strength were measured as indicators of hand function. The amplitude
      and latency of motor-evoked potentials (MEPs) and the duration of the silent
      period in the first dorsal interosseous muscle elicited by transcranial magnetic
      stimulation (TMS) reflected the integrity of excitatory and inhibitory cortical
      circuits. RESULTS: Diminished hand function, small MEPs, and prolonged silent
      period durations were evident in stroke compared with control subjects. Longer
      MEP latencies and smaller amplitudes distinguished subacute from chronic stroke.
      Side-to-side asymmetries were greatest in the subacute group for all TMS
      outcomes, although this lessened over time based on the subsample retested at
      discharge. Greater side-to-side MEP amplitude symmetry and lower motor threshold
      (lesioned side) were associated with better hand function in subacute and chronic
      stroke, respectively. CONCLUSIONS: Cortical excitability is an important
      determinant of hand function poststroke and evolves with the time elapsed since
      the stroke event. The unique neural correlates of hand function evident in
      subacute and chronic stroke may reflect different phases of neuromuscular
      recovery.

PMID- 16635625
TI  - Biomechanic modeling of sit-to-stand to upright posture for mobility assessment
      of persons with chronic stroke.
AB  - OBJECTIVE: To test the suitability of using biomechanic measures associated with
      a minimum measured input model (MMIM) approach to assess mobility of people with
      chronic stroke during the execution of a sit-to-stand (STS) to upright posture
      motor task. DESIGN: Single group, observational. SETTING: Institutional settings
      in the United States and Italy. PARTICIPANTS: Twenty-nine subjects with chronic
      unilateral lower-limb impairments and resultant mobility limitations secondary to
      stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Manual measurement
      of lower-limb strength; performance-based tests including repeated chair
      standing, walking speed, and standing balance; and ground reactions measured with
      a force platform during STS and upright posture. The ground reactions were fed to
      a telescopic inverted pendulum model of the musculoskeletal system. Parameters
      representing the model outputs were compared with performance-based and strength
      measures to assess, respectively, motor ability and impairment-related changes in
      subjects' motor strategies. RESULTS: The parameters derived from the model
      effectively differentiated between motor strategies associated with different
      performance-based scores, and allowed the identification of relevant difficulties
      encountered in STS execution. These difficulties could be associated with
      different strength scores. This was also true for subjects scoring the maximum in
      both performance-based and strength tests. CONCLUSIONS: The MMIM is a relatively
      inexpensive and noninvasive approach that enhances mobility assessment of
      hemiparetic subjects with different motor ability levels. It provides information
      that correlates well with performance-based and strength scores and, in addition,
      it allows for subject-specific motor strategy identification.

PMID- 16635626
TI  - Subjective visual vertical perception relates to balance in acute stroke.
AB  - OBJECTIVE: To determine whether misperception of the subjective visual vertical
      (SVV) underlies balance difficulties in hemiplegic patients. DESIGN: Descriptive
      study, using a convenience sample. SETTING: Department of physical medicine of a
      university hospital. PARTICIPANTS: Thirty inpatients with hemiplegia after a
      hemispheric stroke during the 3 previous months. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The SVV was tested while subjects sat in a dark room and
      were asked to adjust a luminous line to the vertical position. Mean SVV deviation
      and uncertainty, defined as the standard deviation, were calculated for 8 trials.
      Balance was assessed by the Postural Assessment Scale for Stroke (PASS) and while
      patients sat on a laterally rocking platform placed on a Satel force platform.
      The mean body position and the instability score (Lx), calculated as the length
      of the course of the center of pressure, were recorded. Functional outcome was
      also evaluated by the FIM instrument. RESULTS: An abnormal SVV was recorded for
      20 of 30 patients. Balance (ie, PASS, Lx) and FIM correlated significantly with
      SVV tilt (P<.001, P=.01, and P<.001, respectively) and with uncertainty (PASS,
      P=.006; FIM, P=.003). CONCLUSIONS: Verticality misperception was related to poor
      balance and might be an important element in the assessment of contributing
      factors to balance disorders after stroke. It should probably be taken into
      account when establishing balance rehabilitation programs for patients with
      hemiplegia.

PMID- 16635627
TI  - Dimensions of disordered attention in traumatic brain injury: further validation
      of the Moss Attention Rating Scale.
AB  - OBJECTIVES: To investigate the factor structure of disordered attention in
      moderate to severe, acute traumatic brain injury (TBI) and to use factor analysis
      and item response theory to further validate and refine an observational rating
      scale of attention for clinical and research purposes. DESIGN: Multicenter
      inception cohort. SETTING: Inpatient rehabilitation units. PARTICIPANTS: Patients
      with TBI (N=372) consecutively admitted to 8 Traumatic Brain Injury Model System
      centers within 2 weeks prior to observation, who consistently followed commands
      and who were on stable doses of all psychotropic medications for a 3-day rating
      period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Participants were
      rated independently by treating occupational and physical therapists at an
      average of 1 month postinjury on the Moss Attention Rating Scale (MARS), a 45
      item, Likert-type scale of attention-related behavior. RESULTS: Exploratory and
      confirmatory factor analyses revealed 3 correlated factors of disordered
      attention, interpreted as restlessness/distractibility, initiation, and
      sustained/consistent attention. Item response (Rasch) analysis was used to
      eliminate redundant items and to fill gaps in item difficulty. The resulting MARS
      consists of 22 items that can produce 3 factor scores and a total score that
      covers the broad construct of disordered attention. CONCLUSIONS: The factor
      scored MARS has potential utility as a quantitative observational method with
      which to assess and study different dimensions of disordered attention in acute
      TBI, and to monitor change over time and treatment response within these
      dimensions.

PMID- 16635628
TI  - Psychometric properties of a modified Wolf Motor Function test for people with
      mild and moderate upper-extremity hemiparesis.
AB  - OBJECTIVE: To test the necessity of videotaping, test-retest reliability, and
      item stability and validity of a modified Wolf Motor Function Test (WMFT) for
      people with mild and moderate chronic upper-extremity (UE) hemiparesis caused by
      stroke. DESIGN: Raters of videotape versus direct observation; test-retest
      reliability over 3 observations, item stability, and criterion validity with
      upper-extremity Fugl-Meyer Assessment (FMA) in the mildly and moderately impaired
      groups. SETTING: Academic research center. PARTICIPANTS: Sixty-six subjects with
      chronic UE hemiparesis who participated in a large intervention study. Subjects
      were classified into mild and moderate groups for additional analyses.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mean and median times of
      task completion, functional ability, and strength (weight to box) measures of the
      WMFT. FMA scores for validity assessment. RESULTS: In a subgroup of 10 subjects,
      the intraclass correlation coefficient (ICC) for videotape versus direct
      observation ranged from .96 to .99. For the whole group, test-retest reliability
      using ICC2,1 ranged from .97 to .99; stability of the test showed that
      administration 1 differed from administrations 2 and 3 but administrations 2 and
      3 did not differ; item analysis showed that 4 of 17 items changed across time,
      and validity, using a correlation with UE FMA, ranged from .86 to .89. Separate
      mild- and moderate-group analyses were similar to whole-group results.
      CONCLUSIONS: Videotaping the modified WMFT was not necessary for accurate
      scoring. The modified WMFT is reliable and valid as an outcome measure for people
      with chronic moderate and mild UE hemiparesis and is stable, but 1 repeat testing
      is recommended when practical.

PMID- 16635629
TI  - Upper-extremity disability in essential tremor.
AB  - OBJECTIVE: To determine the extent of disability in subjects with essential
      tremor (ET) using time-based, standardized measures of upper-extremity function.
      DESIGN: Descriptive case series. SETTING: Motor performance research laboratory.
      PARTICIPANTS: Thirty subjects with ET (mean age, 58.3+/-13.7 y) and 28 healthy
      controls (mean age, 58.4+/-12.4 y). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: We assessed upper-extremity function using the Box and Block Test,
      Purdue Pegboard Test (PPT), and Test Evaluant la performance des Membres
      superieurs des Personnes Agees (TEMPA). We measured tremor severity with laser
      displacement sensors. RESULTS: Subjects with ET-type tremor in 1 or both hands
      performed significantly worse than controls on all unilateral and bilateral tasks
      (P range, .038-.001) except on the PPT for the dominant side. ET subjects without
      ET-type tremor in the dominant hand also performed significantly worse than
      controls on the TEMPA unilateral tasks (P=.043). Performance on the 3 functional
      measures correlated moderately with tremor severity for the nondominant hand.
      CONCLUSIONS: Subjects with ET show measurable disability on time-based measures
      of upper-extremity function. However, our findings are consistent with other
      reports that tremor severity does not correlate well with disability, especially
      with regard to the dominant upper extremity.

PMID- 16635630
TI  - Joint-angle-dependent neuromuscular dysfunctions at the wrist in persons after
      stroke.
AB  - OBJECTIVE: To evaluate the joint-angle-dependent neuromuscular functions at the
      affected wrist in hemiplegic subjects after stroke while doing isometric maximal
      voluntary wrist flexion and extension across different wrist angles. DESIGN: We
      investigated torques during isometric maximal voluntary wrist flexions and
      extensions at 8 different wrist angles, ranging from -45 degrees to 60 degrees.
      We used the associated electromyographic activities of 2 agonist and antagonist
      muscle pairs related to wrist and elbow joints for the analysis of muscular
      coactivations. We compared the data obtained from poststroke subjects' affected
      and unaffected sides. SETTING: A research laboratory in a rehabilitation center.
      PARTICIPANTS: Eleven subjects with hemiplegia after stroke with passive range of
      motion (ROM) in the wrist from -45 degrees to 60 degrees. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Directly measured torques, torques after
      normalization during maximal isometric wrist contractions, and normalized moving
      average electromyographic signals of each muscle at the tested positions.
      RESULTS: The measured torques of the affected wrists were significantly lower
      than those of the unaffected wrists at all tested angles during wrist flexion and
      extension (P<.05). The angle-dependent patterns of the normalized torque across
      the tested wrist angles varied from those of the unaffected wrists (2-way
      analysis of variance, P<.05). There were decreases in normalized torques during
      both flexion and extension at the extended positions in the affected group
      (P<.05). Abnormal cocontractions were found in agonist and antagonist muscle
      pairs related to wrist and elbow joints, and between the elbow flexor and wrist
      extensor when subjects did the wrist contractions on the paretic side, especially
      at the wrist extended positions. CONCLUSIONS: Wrist muscle weakness was
      distributed unevenly across the selected wrist ROM on the affected side, as
      represented by the varied patterns of the normalized torque-angle relationship,
      compared with the unaffected wrists. There were reductions in the selective
      control of muscle coactivating synergies both single-jointly and cross-jointly in
      the impaired nervous system during wrist contractions; the extent of these
      reductions was also related to the wrist angle configuration.

PMID- 16635631
TI  - Exercise training during hemodialysis improves dialysis efficacy and physical
      performance.
AB  - OBJECTIVE: To determine the impact of a 20-week intradialytic exercise program,
      consisting of 60 minutes of cumulative duration, low-intensity exercise during
      the first 2 hours of dialysis, on dialysis efficacy, physical performance, and
      quality of life in self-care hemodialysis (HD) patients. DESIGN: One-group
      repeated measures. SETTING: Satellite HD units affiliated with a Canadian
      teaching hospital. PARTICIPANTS: A convenience sample of 13 self-care HD patients
      who were stable on dialysis for a minimum of 6 months and were medically screened
      for significant cardiac, pulmonary, and/or musculoskeletal pathology that would
      preclude exercise. INTERVENTION: A 5-month intradialytic exercise program in
      which subjects exercised 3 times a week (cycle ergometer, mini-stepper) for 30
      minutes in each of the first 2 hours of HD. MAIN OUTCOME MEASURES: Dialysis
      efficacy (in single-pool model of urea kinetics [spKt/V]) was assessed prior to
      and at the end of each month of the exercise program. Physical function (6-minute
      walk test [6MWT]), and quality of life. (Kidney Disease Quality of Life-Short
      Form [KDQOL]) were determined at baseline and at weeks 10 and 20 of the exercise
      program. RESULTS: SpKt/V increased 11% at the end of the first month of the
      program (P<.05) and remained elevated for the duration of the program (18%-19%).
      Distance walked on the 6MWT increased by 14% at both weeks 10 and 20 (P<.05). No
      changes were noted in KDQOL scores. CONCLUSIONS: A low-intensity intradialytic
      exercise program is a viable adjunctive therapy, which improves HD efficacy and
      physical function in HD patients.

PMID- 16635632
TI  - Rapid and extensive arterial adaptations after spinal cord injury.
AB  - OBJECTIVE: To assess the time course of adaptations in leg vascular dimension and
      function within the first 6 weeks after a spinal cord injury (SCI). DESIGN:
      Longitudinal study design. SETTING: University medical center and rehabilitation
      clinic. PARTICIPANTS: Six men were studied serially at 1, 2, 3, 4, and 6 weeks
      after SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Diameter, blood
      flow, and shear rate levels of the common femoral artery (CFA), superficial
      femoral artery (SFA), brachial artery, and carotid artery were measured with echo
      Doppler ultrasound (diameter, blood flow, shear rate). Endothelial function in
      the SFA was measured with flow-mediated dilation (FMD). In addition, leg volume
      and blood pressure measurements were performed. RESULTS: Femoral artery diameter
      (CFA, 25%; SFA, 16%; P<.01) and leg volume (22%, P<.01) decreased simultaneously,
      and these reductions were largely accomplished within 3 weeks postinjury.
      Significant increases were observed for basal shear rate levels (64% increase at
      week 3; 117% increase at week 6; P<.01), absolute FMD responses (8% increase at
      week 3, 23% increase at week 6; P<.05) and relative FMD responses (26% increase
      at week 3, 44% increase at week 6; P<.001). CONCLUSIONS: Our findings show a
      rapid onset of adaptations in arterial dimension and function to extreme
      inactivity in humans. Vascular adaptations include extensive reductions in
      femoral diameter and leg volume, as well as increased basal shear rate levels and
      FMD responses, which all appear to be largely accomplished within 3 weeks after
      an SCI.

PMID- 16635633
TI  - Test-retest reliability of isokinetic dynamometry for the assessment of
      spasticity of the knee flexors and knee extensors in children with cerebral
      palsy.
AB  - OBJECTIVE: To assess test-retest reliability of the peak resistance torque and
      slope of work methods of spasticity measurement of the knee flexors and extensors
      in children with cerebral palsy (CP). DESIGN: Test-retest reliability study.
      SETTING: Pediatric orthopedic hospital. PARTICIPANTS: Fifteen children with CP.
      INTERVENTION: Knee extensor and flexor spasticity was assessed with an isokinetic
      dynamometer using passive movements at 15 degrees, 90 degrees, and 180 degrees/s
      taken 1 hour apart. MAIN OUTCOME MEASURES: Peak resistive torque and work were
      calculated. The relative and absolute test-retest reliability was calculated by
      using intraclass correlation coefficients (ICCs) and Bland-Altman plots,
      respectively. RESULTS: Relative reliability was good (ICC>.75) for slope-of-work
      and peak resistance torque measurements at a velocity of 180 degrees/s, whereas
      reliability of peak torque measurements was decreased (ICC<.51) at slower
      velocities for both muscle groups. The 95% limits of agreement of Bland-Altman
      plots contained most data points for both methods, but the width of the limits of
      agreement were wide. CONCLUSIONS: The measurement of spasticity of the knee
      extensors and flexors in children with CP using peak-resistance torque at 180
      degrees/s and the slope of work method has acceptable relative test-retest
      reliability. However, the absolute reliability of spasticity data should be
      considered cautiously.

PMID- 16635634
TI  - Dynamic foot pressure measurements for assessing foot deformity in persons with
      spastic cerebral palsy.
AB  - OBJECTIVES: To identify characteristics of foot pressure distribution in
      different foot deformities using a computerized insole sensor system, and to
      identify changes in these parameters after corrective surgery in children with
      spastic cerebral palsy (CP). DESIGN: Before-after trial. SETTING: University
      hospital. PARTICIPANTS: Sixty-seven limbs of 44 children with spastic CP were
      assessed (35 equinus, 17 equinovarus, 15 equinovalgus). INTERVENTION: Orthopedic
      surgery for foot deformities. MAIN OUTCOME MEASURES: Parameters of foot contact
      pattern, pressure-time integral (PTI), and center of pressure (COP) trajectories
      were assessed before and at a minimum of 6 months postsurgery, using the F-scan
      system. RESULTS: Prior to surgery, the medial midfoot relative impulse, which is
      PTI normalized by a percentage of the entire foot, differed significantly between
      foot deformity groups. Relative impulse was high on the lateral column of the
      foot in the equinovarus group and on the medial column of the foot in the
      equinovalgus group. Center of pressure index (COPI) and coronal index reflecting
      the asymmetry of the medial and lateral columns of the foot differed
      significantly between the equinovalgus and equinovarus groups. After surgery,
      significant changes occurred in foot contact patterns, including total contact
      area, contact length, contact width of hindfoot, and the relative impulse of
      specific areas of the foot. In addition, there were significant changes in the
      parameters of COP, such as anteroposterior displacement, slope, and velocity.
      CONCLUSIONS: In dynamic foot pressure measurements using a computerized insole
      sensor system, the parameters reflecting medial or lateral changes in weight
      bearing, such as COPI and coronal index, appear to be useful for evaluating
      abnormalities and improvements after intervention in the frontal plane, such as
      varus and valgus. Additionally, assessment of parameters in foot contact
      patterns, PTIs, and COP path trajectories appears to be helpful in evaluating
      outcomes after corrective surgery.

PMID- 16635635
TI  - Effects of ankle-foot orthoses on ankle and foot kinematics in patient with ankle
      osteoarthritis.
AB  - OBJECTIVE: To determine if different foot orthoses have a similar effect on foot
      kinematics in subjects with ankle osteoarthritis (OA) when walking on various
      ground conditions. DESIGN: Within-subject comparisons study. SETTING:
      Biomechanics research laboratory. PARTICIPANTS: Thirteen subjects with unilateral
      ankle OA. INTERVENTIONS: Custom-made ankle-foot orthosis (AFO), rigid hindfoot
      orthosis (HFO-R), and articulated hindfoot orthosis (HFO-A) were used by subjects
      when walking on level, ascending and descending ramp, and side-slope conditions.
      MAIN OUTCOME MEASURES: The range of motion of the hindfoot (calcaneus relative to
      tibia) and forefoot (metatarsal relative to calcaneus) was measured using an 8
      camera motion analysis system. RESULTS: The AFO and HFO-R provided the best
      sagittal plane hindfoot motion restriction over all ground conditions (P<.001).
      The HFO-R allowed the greatest sagittal plane forefoot motion when walking over
      level (P=.01) and side-slope (P<.02) conditions, the greatest frontal plane
      forefoot motion walking down the ramp (P=.003), and the greatest transverse plane
      forefoot motion when walking over level (P=.011) and ramp-ascending conditions
      (P=.005). The HFO-A restricted motion of the unaffected joint and did not
      effectively restrict hindfoot motion. CONCLUSIONS: The HFO-R not only provides
      selective restriction to the ankle-hindfoot motion, but also allows sufficient
      forefoot motion compared with the AFO. We consider the HFO-R to be the best
      option of all tested orthoses for treating patients with ankle OA pain arising
      from ankle motion.

PMID- 16635636
TI  - Prosthetic intervention effects on activity of lower-extremity amputees.
AB  - OBJECTIVE: To investigate the effect of prosthetic interventions on the
      functional mobility of lower-extremity amputees. DESIGN: Crossover with repeated
      measures. SETTING: Household and community environment. PARTICIPANTS: Twelve
      transtibial and 5 transfemoral amputees. INTERVENTIONS: For transtibial amputees,
      shock-absorbing versus rigid pylons. For transfemoral amputees, C-Leg versus
      Mauch SNS knees. MAIN OUTCOME MEASURES: Daily activity level (step count) and
      duration (minutes of activity). RESULTS: Pylon type had no effect on the daily
      activity level or duration of transtibial amputees. Knee type had no effect on
      the daily activity level or duration of transfemoral amputees. Transtibial
      amputees were more active on weekdays (3079+/-1515 steps/d) than weekends (2386+/
      1225 steps/d) (P=.007). In general, lower-extremity amputees perform numerous
      short-duration bouts of activity (1-2 min) consisting of fewer than 17 steps/min,
      but activities of more than 15 minutes in duration were relatively rare (<1 per
      day). CONCLUSIONS: Intervention had no effect on amputee activity level and
      duration. Higher weekday activity levels of transtibial amputees suggest their
      vocational activities are more demanding than recreational activities. The
      fitting, alignment, and design of prosthetic components should be optimized for 1
      to 2 minute bouts of activity consisting of only a few dozen steps.

PMID- 16635637
TI  - Symptom change with exercise is a temporary phenomenon for people with multiple
      sclerosis.
AB  - OBJECTIVE: To determine the impact of a single exercise session on function,
      fatigue, and sensory symptoms for people with multiple sclerosis (MS). DESIGN:
      This pilot study was designed as a before-after trial. Demographic and response
      to-exercise measures were taken before exercise, repeated immediately after
      exercise, and followed up again 24 hours later. SETTING: Three metropolitan
      centers of an MS society. PARTICIPANTS: A prospective sample of 34 subjects with
      MS who were referred for physiotherapy for an exercise program and who could
      attend an MS society center. INTERVENTIONS: Subjects performed an individually
      prescribed exercise session, which was at a commencement level and included
      strengthening, stretches, and fitness exercises. Subjects exercised for between 5
      to 45 minutes (mean, 17.4 min) at an intensity of 7 to 17 (median, 12) on the
      Borg rating of perceived exertion (RPE) scale. MAIN OUTCOME MEASURES: All outcome
      measures were self-rated by subjects and included the Borg RPE scale, a
      questionnaire for sensory symptom description, and visual analog scales for
      rating of fatigue, function, and intensity of sensory symptoms. RESULTS:
      Subjective levels of fatigue and function immediately postexercise and 24 hours
      postexercise did not differ significantly from pre-exercise levels. However, over
      40% of subjects experienced a temporary increase in number of sensory symptoms,
      44% experienced an increase in the intensity of sensory symptoms, and 29%
      experienced an increase in both number and intensity immediately postexercise.
      CONCLUSIONS: This small study found that when people with MS undertake exercise
      at a commencement level, they can expect that sensory symptoms may change
      temporarily, but they are unlikely to have any deleterious changes in fatigue and
      function.

PMID- 16635638
TI  - Alien hand syndrome in stroke: a report of 2 cases and review of the literature.
AB  - Alien hand syndrome (AHS) is a rare condition that occurs in patients with brain
      injury. It has also been described in stroke subjects, after callosotomy, and in
      corticobasal degeneration. The common feature of AHS is the involuntary
      autonomous activity of the affected extremity that is perceived as being
      controlled by an external force. AHS as a nosologic entity has been challenged. A
      complex variety of abnormal involuntary motor behaviors may follow cerebral
      lesions in different cerebral locations such as the corpus callosum, the
      parietal, or frontal regions. Although different subtypes of AHS have been
      distinguished, this classification clearly does not cover the wide clinical
      variety of abnormal (involuntary) motor behaviors of the upper extremity. In this
      report, we provide a review of literature on abnormal involuntary motor behaviors
      of the upper extremity after a stroke, which may help to improve early
      recognition of AHS and facilitate adjustment of rehabilitation therapy.
      Furthermore, we briefly discuss the complex variety of abnormal, involuntary
      motor behaviors that may follow after cerebral lesions, their anatomic
      substrates, the underlying mechanisms, and the prognosis.

PMID- 16635639
TI  - Walking with a rollator and the level of physical intensity in adults 75 years of
      age or older.
AB  - OBJECTIVE: To determine whether walking with a rollator by persons 75 years of
      age or older is of sufficient intensity to improve aerobic fitness. DESIGN: A
      cross-sectional cohort study. SETTING: University movement laboratory.
      PARTICIPANTS: Fifteen subjects 75 years of age or older (mean age, 83.7 y) who
      could only walk by using a rollator. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: During 6 minutes of self-paced treadmill walking using a rollator at a
      mean walking speed of 0.6 m/s, oxygen uptake (Vo2), carbon dioxide production,
      and heart rate were determined. Respiratory exchange ratio (RER) and energy
      expenditure were calculated. The energy expenditure was expressed as the number
      of metabolic equivalents (METS), the percentage of estimated maximal Vo2
      (Vo2max), the percentage of estimated Vo2max reserve, and the percentage of
      estimated maximal heart rate. RESULTS: Mean Vo2 was .718 L/min. Mean RER was .93
      (95% confidence interval [CI], .89-.97). Thirteen participants showed an RER
      below 1.0, which indicates a negligible contribution of anaerobic expenditure.
      Walking with a rollator required a mean of 2.8 (95% CI, 2.4-3.2) METS, 71.9% of
      Vo2max (95% CI, 65.2%-78.6%), 50.5% (95% CI, 39.4%-61.5%) of Vo2 reserve, and
      75.2% (95% CI, 67.6%-82.8%) of estimated maximal heart rate. CONCLUSIONS: For
      people 75 years of age or older, walking with a rollator is an activity of
      moderate to high level of intensity, with the capacity of improving aerobic
      fitness.

PMID- 16635640
TI  - Bringing preconditioning and postconditioning into focus.

PMID- 16635641
TI  - Epsilon protein kinase C as a potential therapeutic target for the ischemic
      heart.
AB  - Ischemic heart disease is the leading cause of morbidity and mortality in the
      western world. Ischemic damage can occur by acute myocardial infarction, stable
      angina, cardiac stunning, and myocardial hibernation. In addition, 'scheduled'
      ischemic events, occurring during cardiac surgery, heart transplantation, and
      elective angioplasty, can also result in cardiac damage. Ischemic or
      pharmacological preconditioning can decrease the extent of damage to the
      myocardium. Although the mechanism of preconditioning-mediated cardioprotection
      is not fully understood, epsilonPKC has been implicated as a critical mediator of
      this process in animal studies. The use of isozyme-specific pharmacological tools
      has permitted a better elucidation of the upstream stimuli and the downstream
      transducers of epsilonPKC in the pathways leading to cardioprotection. While
      little is known about the role of epsilonPKC in these pathways in humans, animal
      studies suggest a potential therapeutic role of epsilonPKC. This review will
      focus on the role of epsilonPKC in cardiac protection and on the signal
      transduction cascades that have been implicated in this protection.

PMID- 16635642
TI  - The end-effectors of preconditioning protection against myocardial cell death
      secondary to ischemia-reperfusion.
AB  - Our understanding of the end-effectors involved in preconditioning protection is
      still very limited. This is partially due to an incomplete knowledge of the
      mechanisms responsible for acute sarcolemmal rupture and cell death during the
      first minutes of reperfusion, including the relative roles of hypercontracture
      mediated sarcolemmal rupture and mitochondrial permeability transition pore
      (MPTP) opening-mediated cell death. In the present article, the role of proposed
      end-effectors of preconditioning protection, defined as molecules directly
      involved in cell death that are modified by ischemic preconditioning (IP), is
      examined. IP attenuates hypercontracture-mediated cell death, probably through
      several mechanisms, including attenuated calpain activation during reperfusion
      leading to preserved cytoskeletal integrity and accelerated recovery of Na+/K+
      ATPase function, but probably also protein kinase G (PKG)-mediated improved
      calcium handling. The potential role of gap junctions in preconditioning
      protection is controversial, but the recently discovered mitochondrial
      localisation of connexin43 seems to play an important role in protection that has
      not yet been completely defined. Several recent studies suggest that IP can
      reduce MPTP opening during reperfusion and limit infarct size through this
      mechanism, although the contribution of this widely accepted mechanism to the
      infarct size reduction induced by IP in the intact heart needs to be established.

PMID- 16635643
TI  - Comparisons of perceived quality of life across clinical states in bipolar
      disorder: data from the first 2000 Systematic Treatment Enhancement Program for
      Bipolar Disorder (STEP-BD) participants.
AB  - BACKGROUND: Evidence indicates that quality of life is subnormal in patients with
      bipolar disorder and that it differs across mood states. However, the pattern of
      specific deficits has not been well studied, and the role of potential
      confounders has received no attention. METHOD: We investigated the self-reported
      quality of life, Medical Outcomes Study 36-Item Short Form (SF-36), and Quality
      of Life Enjoyment and Satisfaction (QLESQ) at baseline across the clinical states
      of the first 2000 participants enrolled in Systematic Treatment Enhancement
      Program for Bipolar Disorder. RESULTS: Bivariate analyses indicated significant
      differences across mood state, with depressive symptoms predicting lower SF-36
      mental and physical scores and QLESQ overall score. However, adjustment for
      relevant clinical and demographic variables erased the difference in the SF-36
      physical score. Notably, covariate adjustment removed the apparently
      "supranormal" SF-36 mental and QLESQ scores among those with mania/hypomania
      compared with those euthymic. CONCLUSION: Depressive symptoms are a strong
      predictor of quality of life, yet covariate adjustment has an impact as well.
      Clinically, this indicates the need for addressing these factors if quality of
      life is to be maximized. Such factors should also be taken into account in future
      naturalistic and clinical trials research on quality of life in bipolar disorder.

PMID- 16635644
TI  - A multiwave multi-informant study of the specificity of the association between
      parental and offspring psychiatric disorders.
AB  - The present study was conducted to investigate the specificity of the association
      between parental and offspring psychiatric disorders using epidemiological data
      from a series of parent and offspring interviews. A community-based sample of 593
      mothers and their offspring from upstate New York were interviewed during the
      adolescence and early adulthood of the offspring. The children of parents with
      generalized anxiety disorder were at specifically elevated risk for anxiety
      disorders when co-occurring psychiatric disorders were controlled. The
      associations between parental and offspring antisocial, conduct, depressive, and
      substance use disorders were characterized by modest specificity. Children of
      parents with externalizing disorders were nearly as likely to develop
      internalizing disorders as they were to develop externalizing disorders. Children
      of parents with internalizing disorders were somewhat, but not significantly,
      more likely to develop internalizing disorders. These findings support the
      inference that children of parents with generalized anxiety disorder may be more
      likely to develop anxiety disorders than they are to develop other psychiatric
      disorders. However, when co-occurring psychiatric disorders are accounted for,
      the children of parents with depressive, disruptive, and substance use disorders
      may be as likely to develop other disorders as they are to develop the same type
      of disorder that their parents have had.

PMID- 16635645
TI  - Personality disorders and quality of life. A population study.
AB  - The purpose of the study was to investigate the relationship between specific
      personality disorders (PDs) and specific aspects of quality of life in the common
      population. The sample consisted of 2053 individuals between 18 and 65 years old.
      Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM
      III-R), axis I was studied by means of a structured interview (Composite
      International Diagnostic Interview) and axis II by means of a Structured
      Interview for DSM-III-R Personality Disorders; sociodemographic variables were
      taken into account, and broad aspects of quality of life were included.
      Personality disorders appeared to be more important statistical predictors of
      quality of life than sociodemographic variables, somatic health, and axis I
      disorder. Those with avoidant, schizotypal, paranoid, schizoid, and borderline
      PDs had the strongest and broadest reduction in quality of life, whereas those
      with histrionic, obsessive-compulsive, passive-aggressive, and sadistic PDs did
      not show any reduction. A number of specific relationships occurred. Furthermore,
      the more PDs that existed and the more personality criteria fulfilled, the poorer
      the quality of life, pointing to the importance of comorbidity and continuity.

PMID- 16635646
TI  - Validity of a self-report depression symptom scale for identifying remission in
      depressed outpatients.
AB  - In treatment studies of depression, remission is usually defined by scoring less
      than a threshold value on an interview-based measure of depression severity such
      as the Hamilton Rating Scale for Depression (HRSD). Although it has been
      recommended that measures such as the HRSD be used by clinicians in clinical
      practice to evaluate remission status, the time demands of clinical practice
      limit the feasibility of this suggestion. Self-report questionnaires are a cost
      effective option to thoroughly, systematically, reliably, and validly evaluate
      clinical status because they are inexpensive in terms of professional time needed
      for administration and do not require special training for administration. In a
      previous report from the Rhode Island Methods to Improve Diagnostic Assessment
      and Services project, we derived a cutoff on a self-report depression
      questionnaire corresponding to the widely used definition of remission on the
      HRSD (ie, < or = 7). In the present report, we examined the validity of this
      questionnaire as an indicator of remission among patients who responded to
      antidepressant treatment. Specifically, we examined psychosocial functioning in
      treatment responders who were and were not in remission according to the self
      report symptom scale. In a sample of 371 depressed outpatients who were judged by
      their treating psychiatrists as having responded to treatment, 250 scored in the
      remission range on the symptom scale. Compared with treatment responders whose
      depression was not in remission, the patients who were in remission reported
      significantly less psychosocial impairment and significantly better quality of
      life and were significantly more likely to assert that they are in remission from
      their depression. These findings support the validity of a self-report depression
      questionnaire as an index of remission status among treatment responders.

PMID- 16635647
TI  - Treatment of eating disorders improves eating symptoms but not alexithymia and
      dissociation proneness.
AB  - BACKGROUND: Eating disorders have been reported to increase in frequency, but it
      is yet unclear what psychological characteristics increase the proneness toward
      the development of eating disorders. Alexithymia (AL; a difficulty in awareness
      to one's emotions) and dissociation proneness are 2 such plausible features.
      METHOD: In this study, we evaluated the efficacy of a combined intervention
      (group therapy, individual therapy, and pharmacologic therapy) in a group of
      soldiers with eating disorders (n = 30) in the Israel Defense Forces. Moreover,
      we examined whether AL and dissociation proneness were frequent in this group and
      whether clinical improvement was associated with an improvement in these factors
      as well. RESULTS: High scores on the AL and dissociation measures were noted. The
      intervention was associated with a 50% decrease in the Eating Attitudes Test and
      Eating Disorders Inventory scores, consistent with our clinical impression of
      improvement in the eating symptoms. However, the decrease observed on the
      Dissociative Experiences Scale and Toronto Alexithymia Scale scores was minimal.
      CONCLUSIONS: The combined intervention was efficient in our sample of patients
      with eating disorder despite the small sample size. The aforementioned specific
      psychometric change may be indicative of the lack of importance of changes in AL
      or dissociation proneness in the short-term improvement in patients with eating
      disorder.

PMID- 16635648
TI  - Can structured interviews for posttraumatic stress disorder assist clinical
      decision-making after motor vehicle accidents? An exploratory analysis.
AB  - Motor vehicle accidents (MVAs) represent one of the most common causes of
      posttraumatic stress disorder (PTSD) worldwide. Predicting those MVA survivors
      who are likely to experience PTSD in the longer-term has attracted substantial
      research attention, but most investigators have concluded that early traumatic
      stress symptoms have only moderate predictive power. The present study focuses on
      a decision-tree approach that might be useful to clinicians attempting to
      identify subgroups of MVA survivors with graduated degrees of risk. Eighty-three
      consecutive MVA admissions (response rate, 65%) were assessed by structured
      clinical interview within 2 weeks of the accident and at 18 months follow-up.
      Meeting full criteria for PTSD (other than the time criterion) at baseline
      achieved a positive predictive power of 0.92 in identifying those who had PTSD
      over the following 18 months. For the remainder, the PTSD "arousal" domain
      achieved a positive predictive power of 0.81 for predicting those with either
      subthreshold PTSD or full PTSD over the 18-month follow-up period. The
      implications for further research into a stepped approach to intervention and
      monitoring are discussed.

PMID- 16635649
TI  - Clinical significance of lifetime mood and panic-agoraphobic spectrum symptoms on
      quality of life of patients with rheumatoid arthritis.
AB  - BACKGROUND: Previous studies suggested that rheumatoid arthritis (RA) is
      associated with depressive and anxiety symptomatology. The well-being and
      functioning of patients with RA may be significantly influenced by subthreshold
      psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with
      RA, compared with the Italian norms and patients with diabetes, was assessed by
      the influence of lifetime mood and panic-agoraphobic spectrum symptoms and
      demographic and clinical variables. METHODS: Ninety-two patients were
      consecutively recruited at the Department of Rheumatology at the University
      Hospital of Pisa, Italy. All patients met diagnostic criteria of RA according to
      the American College of Rheumatology. Health-related quality of life was measured
      using the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire
      (MOS SF-36). Mood and panic-agoraphobic spectra were assessed by two different
      structured self-report instruments: the Mood Spectrum (MOODS-SR) and the Panic
      Agoraphobic Spectrum (PAS-SR), respectively. RESULTS: Patients with RA were
      compared, as regards the MOS SF-36 scale scores, with the Italian normative
      population and patients with diabetes. Compared with the Italian population,
      patients with RA showed significantly lower MOS SF-36 scale scores, except for
      role emotional. Moreover, patients with RA scored significantly lower on the role
      physical, bodily pain, and social functioning scales compared with patients with
      diabetes and higher on role emotional and mental health. A significant worsening
      of all MOS SF-36 scale scores was related to higher scores of the depressive
      domains of MOODS-SR, except for social functioning and bodily pain. A
      statistically significant negative association was also found between PAS-SR
      total score and the MOS SF-36 scales physical functioning, vitality, role
      emotional, and mental health. There were no statistically significant
      correlations between MOS SF-36 scales and the manic MOODS spectrum. In the
      multivariate models, the negative correlations between depressive MOODS, role
      emotional, and mental health were confirmed and the severity of arthritis showed
      a significant impact on all MOS SF-36 areas with the exception for social
      functioning; moreover, manic MOODS was associated with better general health.
      CONCLUSIONS: The present report shows that lifetime depressive spectrum symptoms
      negatively affects HRQoL of patients with RA and subthreshold mania improves the
      perception of general health. Diagnosis and appropriate clinical management of
      depression, including subthreshold symptoms, might enhance HRQoL in these
      patients.

PMID- 16635650
TI  - Psychopathological profile of 35% CO2 challenge test-induced panic attacks: a
      comparison with spontaneous panic attacks.
AB  - Our aim was to describe the clinical features of 35% CO2-induced panic attacks in
      patients with panic disorder (PD) (Diagnostic and Statistical Manual and Mental
      Disorders, Fourth Edition) and compare them with the last spontaneous panic
      attack in patients with PD who had not had a panic attack after the 35% CO2
      challenge test. We examined 91 patients with PD submitted to the CO2 challenge
      test. The test consisted of exhaling as fully as possible, took a fast vital
      capacity breath, held their breath for 8 seconds, exhaled, and then repeated the
      fast vital capacity breath, again holding for 8 seconds. The patients inhaled the
      35% CO2/65% O2 mixture or atmospheric compressed air, randomly selected in a
      double-blind design. Scales were applied before and after the test. A total of
      68.1% (n = 62) patients with PD had a panic attack (responders) after the CO2
      test (chi2(1) = 25.87, P = .031). The last spontaneous panic attack and the
      symptom profile from the patients with PD who had not had a panic attack after
      the test (n = 29, 31.9%) were described to compare. The responders had more
      respiratory symptoms (chi2(1) = 19.21, P < .001), fulfilling the criteria for
      respiratory PD subtype (80.6%); the disorder started earlier (Mann-Whitney, P <
      .001), had a higher familial prevalence of PD (chi2(1) = 20.45, P = .028), and
      had more previous depressive episodes (chi2(1) = 27.98, P < .001). Our data
      suggest that there is an association between respiratory PD subtype and
      hyperreactivity to a CO2 respiratory challenge test. The responders may be a
      subgroup of respiratory PD subtype with future diagnostic and therapeutic
      implications.

PMID- 16635651
TI  - Comorbid psychiatric disorders, sex, and methamphetamine use in adolescents: a
      case-control study.
AB  - The purpose of this case-control study was to elucidate the relative proportions
      of amphetamine use disorder (AUD) and amphetamine-induced disorder (AID) in a
      group of adolescents with the use of methamphetamine (MAMP) and to examine the
      risks for psychiatric comorbidity and sex for MAMP use. Psychiatric comorbidity
      in the preceding year was determined for 200 adolescent MAMP users and 400 drug
      free control subjects by diagnostic interview using the Kiddie epidemiologic
      version of the Schedule for Affective Disorders and Schizophrenia. The
      proportions of AUD and AID were calculated, and the association between
      psychiatric comorbidity, sex, and MAMP use was assessed. The results revealed
      that among the MAMP users, 65 subjects (32.5%) had AUD, whereas 19 (9.5%) had
      AID. Early use of MAMP use was seen in AUD, whereas high-frequency MAMP use was
      associated with the occurrence of AID. Alcohol, nicotine, and betel nut use
      disorders were more prevalent in MAMP users for both sexes. By applying
      conditional logistic regression analysis, it was demonstrated that MAMP use was
      associated with conduct disorder in males, whereas in females, it was associated
      with conduct disorder and adjustment disorder. The results indicated that age of
      first use and subsequent frequency of MAMP use appeared to be associated with the
      development of amphetamine-related disorders. Sex differences in the association
      between psychiatric comorbidity and MAMP use were demonstrated. These factors
      have to be taken into consideration when intervening for adolescent MAMP use.

PMID- 16635652
TI  - Causes of schizophrenia reported by family members of urban African American
      hospitalized patients with schizophrenia.
AB  - Family members often provide psychosocial support and assistance in seeking
      treatment for individuals with schizophrenia. It is crucial to understand what
      family members believe to be the causes of schizophrenia, as this likely
      influences the family's help-seeking decisions. The aim of this descriptive study
      was to investigate the causes of schizophrenia reported by family members of
      African Americans hospitalized with schizophrenia. Sixty-one family members of 38
      patients with a first episode or an acute exacerbation of persistent illness were
      administered a survey containing 30 possible causes of schizophrenia from 5
      categories. The sample endorsed predominantly biologic causes. Many family
      members also endorsed personality and societal causes, as well as family and
      esoteric causes. Compared with family members in the persistent group, family
      members in the first-episode group were more likely to select personality or
      societal causes in addition to biologic causes. These results provide insight
      into the etiologic beliefs of a sample of African American family members.
      Further research is needed to assess the potential influence of these beliefs on
      treatment seeking on the part of the family.

PMID- 16635653
TI  - Tests of a symptom checklist to screen for comorbid psychiatric disorders in
      alcoholism.
AB  - In the treatment of substance use disorders, it is advantageous to identify
      patients with comorbid (nonsubstance) psychiatric disorders because treating
      comorbid disorders improves outcome. Because accurate psychiatric diagnosis is
      time-consuming, there is a need for strategies to screen for these comorbid
      conditions. This study used receiver operating characteristic analysis to
      investigate a symptom checklist (revised Symptom Checklist 90 [SCL-90-R]) as a
      screening instrument for comorbid conditions diagnosed using the Structured
      Clinical Interview for DSM-IV in 171 primarily military personnel with alcohol
      use disorders. Several approaches to applying receiver operating characteristic
      analysis to this problem are demonstrated. Although these results require
      replication in other populations, the SCL-90-R performed well in predicting
      comorbid conditions, with an area under the curve of 0.88 for current and 0.85
      for lifetime comorbid diagnoses. Self-report symptom checklists such as the SCL
      90-R may be useful in screening substance rehabilitation patients for more
      detailed psychiatric assessment and may prove clinically useful in the assessment
      of alcoholic patients.

PMID- 16635654
TI  - A quick and reliable screening measure for OCD in youth: reliability and validity
      of the obsessive compulsive scale of the Child Behavior Checklist.
AB  - BACKGROUND: The high prevalence and morbidity of obsessive compulsive disorder
      (OCD) in youth, the secretive nature of the disorder leading to under
      recognition, and the lack of specialized child psychiatry services in many areas
      suggest that a simple, quick, and reliable screening tool to identify cases could
      be very useful to clinicians who work with children. METHOD: We used 8 items from
      the Child Behavior Checklist (CBCL), an empirically derived instrument free of
      clinician bias, to investigate the usefulness of a previously reported CBCL-based
      obsessive compulsive scale (OCS) by Nelson et al [Nelson EC, Hanna GL, Hudziak
      JJ, Botteron KN, Heath AC, Todd RD. Obsessive-compulsive scale of the Child
      Behavior Checklist: Specificity, sensitivity, and predictive power. Pediatrics
      2001;108(1):E14] in a separate cohort of youth with OCD. We computed the
      psychometric properties of the OCS in our sample of youth with OCD and in
      psychiatric and normal controls, and compared these to the published values.
      RESULTS: Using the recommended cutoff between the 60th and 70th percentiles of
      the OCS to best predict the presence of OCD, we found very high sensitivity (92%
      78%), specificity (86%-94%), negative predictive value (96%-90%), and positive
      predictive value (77%-86%). CONCLUSIONS: The OC scale of the CBCL shows good
      reliability and validity and acceptable psychometric properties to help
      discriminate youth with OCD.

PMID- 16635655
TI  - Clinical and pathologic findings of paraneoplastic dermatoses.
AB  - Paraneoplastic dermatoses comprise a heterogeneous group of noninherited skin
      conditions that manifest internal malignancy. Familiarity with paraneoplastic
      dermatoses is important to both clinician and pathologist alike, as recognition
      of such a condition offers opportunity for early diagnosis and treatment of
      internal malignancy; monitoring for tumor recurrence; and insight into
      pathophysiology which may yield possible clues to treatment. Herein are reviewed
      16 of the best established paraneoplastic dermatoses that display distinctive
      clinical and pathologic findings. LEARNING OBJECTIVE: At the conclusion of this
      leaning activity, participants should be able to recognize, diagnose, and
      describe the clinical and pathologic findings of paraneoplastic dermatoses.

PMID- 16635656
TI  - Large or multiple congenital melanocytic nevi: occurrence of neurocutaneous
      melanocytosis in 1008 persons.
AB  - BACKGROUND: There is a dearth of information regarding the occurrence of
      neurocutaneous melanocytosis (NCM) in a large cohort of persons with large
      congenital melanocytic nevi (LMCN) or multiple congenital melanocytic nevi
      (MCMN). OBJECTIVE: The purpose of this article is to report occurrence of NCM and
      other complications in 1008 persons having LCMN or MCMN. METHODS: Evaluation of
      information obtained from a database of persons with LCMN or MCMN voluntarily
      submitted by the affected persons to a nevus support group, the Nevus Network.
      RESULTS: Of those with truncal LCMN, 6.8% developed significant complications,
      4.8% developed symptomatic NCM, and 2.3% died from either benign or malignant NCM
      or cutaneous melanoma. Of the 4.8% of persons with a truncal nevus who developed
      symptomatic NCM, 34% died. Of those with head or extremity LCMN, 0.8% developed
      symptomatic NCM, and, to date, none have died from any cause. Of the small number
      with MCMN without a giant nevus, 71% developed symptomatic NCM, and 41% died of
      it. LIMITATIONS: Attending physician confirmation of submitted information was
      unavailable. CONCLUSIONS: LCMN of the trunk were associated with a relatively low
      occurrence of medical complications and death in our group, considering the large
      nevomelanocytic burden present. If symptomatic NCM developed in those with
      truncal nevi, the occurrence of death rose to a third. LCMN of the head or
      extremity were associated with minimal medical complications and no deaths. In
      contrast, most of the rare persons (N = 17) with MCMN developed symptomatic NCM,
      and more than a third died.

PMID- 16635657
TI  - A retrospective cohort study of Southeast Asian patients with large congenital
      melanocytic nevi and the risk of melanoma development.
AB  - BACKGROUND: The lifetime risk of developing melanoma in Caucasian patients with
      large congenital melanocytic nevi (LCMN) is estimated to be between 4.5% and 10%.
      Cohort studies of LCMN and the risk of melanoma development in an Asian
      population are not available. OBJECTIVE: We sought to determine the risk of
      melanoma development in a retrospective cohort of patients presenting with LCMN
      to a dermatology tertiary referral center in Singapore from January 1989 to
      December 2004. METHODS: Patients with congenital melanocytic nevi (CMN) that
      covered at least 5% of the body surface area were included in the study. Data
      were obtained from electronic records and photographic documentation. A search
      for malignancy was done using the National Cancer Registry database. RESULTS: In
      all, 39 patients (23 male and 16 female) met the study criteria of LCMN; 15 of 39
      patients also met the criteria of having a giant CMN (ie, a CMN that is predicted
      to be at least 20-cm diameter in adulthood). There were 29 Chinese, 6 Malay, 1
      Indian, and 3 Caucasian patients. Their ages ranged from 23 months to 60 years
      (mean 18.8 years). They presented at a mean age of 26 months and were followed up
      for an average of 16.9 years. The size of the LCMN ranged from 5% to 40% of body
      surface area, with a mean of 12.2%. The most common sites were the back (54%),
      lower limb (28%), and abdomen (26%). Satellite lesions were present in 22
      patients. Magnetic resonance imaging of the head or thoracolumbar spine was
      performed in 7 patients with LCMN on the scalp/face or back, respectively; all
      produced normal findings. Only one patient was treated: he had carbon-dioxide
      laser ablation and Q-switched neodymium:yttrium-aluminum-garnet laser treatment
      of a small part of his LCMN. Skin biopsies were done in 5 patients who had
      developed nodules; histology showed no evidence of malignancy. No patients had
      developed any form of malignancy. LIMITATIONS: The addition of 3 adult patients
      born before the start of the cancer registry may have led to survivor bias. The
      small sample size did not allow a precise estimate of the risk of melanoma
      development in our study population. CONCLUSION: The risk of melanoma development
      in LCMN within a predominantly Southeast Asian cohort appears to be very low.
      Prophylactic complete excision of LCMN is ideal, but seldom achievable. Hence,
      patient education, regular melanoma surveillance, and biopsy of suspicious
      lesions are very important.

PMID- 16635658
TI  - Presentation and detection of invasive melanoma in a high-risk population.
AB  - BACKGROUND: Early detection of melanoma has been encouraged in Queensland for
      many years, yet little is known about the patterns of detection and the way in
      which they relate to tumor thickness. OBJECTIVE: Our purpose was to describe
      current patterns of melanoma detection in Queensland. METHODS: This was a
      population-based study, comprising 3772 Queensland residents diagnosed with a
      histologically confirmed melanoma between 2000 and 2003. RESULTS: Almost half
      (44.0%) of the melanomas were detected by the patients themselves, with
      physicians detecting one fourth (25.3%) and partners one fifth (18.6%). Melanomas
      detected by doctors were more likely to be thin (<0.75 mm) than those detected by
      the patient or other layperson. Melanomas detected during a deliberate skin
      examination were thinner than those detected incidentally. LIMITATIONS: Although
      a participation rate of 78% was achieved, as in any survey, nonresponse bias
      cannot be completely excluded, and the ability of the results to be generalized
      to other geographical areas is unknown. CONCLUSION: There are clear differences
      in the depth distribution of melanoma in terms of method of detection and who
      detects the lesions that are consistent with, but do not automatically lead to,
      the conclusion that promoting active methods of detection may be beneficial.

PMID- 16635659
TI  - A randomized, double-blind, placebo-controlled trial of photopheresis in systemic
      sclerosis.
AB  - BACKGROUND: Systemic sclerosis is a multisystemic connective tissue disease with
      marked involvement of the skin and joints for which few effective evidence based
      therapies are available. To further investigate the efficacy of extracorporeal
      photochemotherapy on early aggressive cutaneous disease, a randomized, double
      blind, placebo-controlled trial was performed. OBJECTIVE: Our aim was to evaluate
      the efficacy of photopheresis in the treatment of patients with systemic
      sclerosis (scleroderma). METHODS: This randomized, double-blind, placebo
      controlled clinical trial was conducted at 16 investigational sites in the United
      States, Canada, and Europe. Sixty-four patients with typical clinical and
      histologic findings of scleroderma, of less than 2 years' duration, were studied.
      Patients did not receive any other concomitant treatment for scleroderma.
      Patients were randomized to receive either active or sham photopheresis treatment
      on two consecutive days monthly for 12 months. Severity of skin (skin scores
      assessed in 22 body regions) and joint involvement (60 joints examined for
      contractures) were assessed on a monthly basis. RESULTS: A statistically
      significant improvement in skin scores as compared with baseline was observed at
      6 months (P = .0024) and 12 months (P = .008) among those who received active
      photopheresis, but not among those who received sham photopheresis. Comparison of
      skin scores between the two study arms did not achieve statistical significance
      because of the small sample size of the study arms. Joint involvement was also
      significantly improved after 6 months (P = .002) and 12 months (P = .001) of
      active photopheresis when compared with baseline. LIMITATIONS: The study lacks
      sufficient statistical power to reveal a significant difference in skin and joint
      manifestations between the active and sham photopheresis arms. CONCLUSION:
      Photopheresis induced significant improvement of skin and joint involvement in
      patients with scleroderma of recent onset; however, any effect when compared with
      sham treatment and a possible placebo effect may be modest.

PMID- 16635660
TI  - Fibrous hamartoma of infancy: an Italian multi-institutional experience.
AB  - BACKGROUND: Fibrous hamartoma (FH) of infancy is a benign mesenchymal tumor,
      occurring as a superficial mass. Complete excision is curative. OBJECTIVE AND
      METHODS: The clinical features and treatment results of 18 children with FH are
      described. RESULTS: Local excision was the most common procedure. Surgery was
      radical in 10 patients, with microscopic residual disease in 6; all of them are
      alive with no evidence of disease 2 to 49 months after diagnosis. One patient,
      treated with a local reexcision for macroscopic residual disease (and
      chemotherapy for a synchronous desmoid fibromatosis) is well 83 months after
      diagnosis; the last patient, with a lesion of the labia majora, only underwent
      biopsy and is doing well, awaiting plastic surgery. LIMITATIONS: The results did
      not reach statistical significance due to difficulties in collecting cases.
      CONCLUSIONS: FH should be treated by complete excision; in our experience a
      nonradical excision was also able to achieve the cure. An aggressive approach
      should be avoided, as the overall prognosis is excellent.

PMID- 16635661
TI  - A comparison of Q-switched alexandrite laser and intense pulsed light for the
      treatment of freckles and lentigines in Asian persons: a randomized, physician
      blinded, split-face comparative trial.
AB  - BACKGROUND: Q-switched (QS) pigmented lasers and intense pulsed light (IPL)
      successfully treat pigment disorders. OBJECTIVE: We sought to compare efficacy
      and side effects of QS alexandrite laser (QSAL) and IPL for freckle and lentigo
      treatment in Asians. METHODS: In all, 15 patients with freckles and 17 patients
      with lentigines were treated randomly with one session QSAL in one cheek and two
      sessions IPL in the other cheek at 4-week intervals. Efficacy was determined
      using a new pigmentation area and severity index score. RESULTS: All patients
      experienced improvement (P < .0001). Postinflammatory hyperpigmentation developed
      in one patient with freckles and 8 patients with lentigines after QSAL. No
      postinflammatory hyperpigmentation occurred after IPL. Freckles achieved greater
      improvement after QSAL than IPL (P = .04). In lentigines, the results after IPL
      were better than QSAL among those with postinflammatory hyperpigmentation after
      QSAL. LIMITATIONS: Limitations include a small case number and short follow-up
      period. CONCLUSION: QSAL was superior to IPL for freckle treatment. IPL should be
      used for lentigines in Asian persons.

PMID- 16635662
TI  - Expression of the heat shock protein-27 in the adult human scalp skin and hair
      follicle: hair cycle-dependent changes.
AB  - BACKGROUND: Heat shock protein (HSP) is a molecular chaperone involved in protein
      folding, assembly, and transport and in the regulation of cell growth and
      differentiation. HSP27 protein is expressed in murine hair follicle (HF) and in
      human skin during fetal development. In this investigation we hypothesized that
      HSP27 protein is expressed in the human scalp skin and its expression in HF
      changes with the transitions form anagen --> catagen --> telogen stages. METHODS:
      To test this hypothesis, the immunoreactivity of HSP27 protein was examined in
      human scalp skin by immunofluorescent method. A total of 50 normal human scalp
      skin biopsy specimens were examined (healthy women, age 53-57 years). In each
      case, 50 HF were analyzed (35, 10, and 5 follicles in anagen, catagen, and
      telogen, respectively). RESULTS: HSP27 protein expression was prominent in human
      scalp anagen, and weak in both catagen and telogen HFs. Within HF, HSP27 protein
      immunoreactivity was prominent in the outer root sheath, inner root sheath,
      precorteocytes, and corteocytes of the hair shaft. In addition, HSP27 protein
      expression was prominent in the epidermis, sebaceous glands, sweat glands, and
      arrector pili muscles. LIMITATIONS: Only some types of heat shock proteins are
      known to date. Also, our knowledge about the exact molecular mechanisms involved
      in the interactions among these protein and other molecular chaperones is still
      incomplete. CONCLUSIONS: Our investigation reports, for the first time, the
      expression patterns of HSP27 in human scalp skin and HF. The differential
      expression of HSP27 during HF cycling suggests its possible roles in human HF
      biology.

PMID- 16635663
TI  - The use of topical calcineurin inhibitors in dermatology: safety concerns. Report
      of the American Academy of Dermatology Association Task Force.

PMID- 16635664
TI  - The diagnosis and treatment of iron deficiency and its potential relationship to
      hair loss.
AB  - Iron deficiency is the world's most common nutritional deficiency and is
      associated with developmental delay, impaired behavior, diminished intellectual
      performance, and decreased resistance to infection. In premenopausal women, the
      most common causes of iron deficiency anemia are menstrual blood loss and
      pregnancy. In men and postmenopausal women, the most common causes of iron
      deficiency anemia are gastrointestinal blood loss and malabsorption. Hemoglobin
      concentration can be used to screen for iron deficiency, whereas serum ferritin
      concentration can be used to confirm iron deficiency. However, the serum ferritin
      concentration may be elevated in patients with infectious, inflammatory, and
      neoplastic conditions. Other tests may be needed, such as erythrocyte zinc
      protoporphyrin concentration, transferrin concentration, serum iron
      concentration, and transferrin saturation. The cause of iron deficiency must be
      identified. If the patient is male, postmenopausal female, or has risk factors
      for blood loss, then the patient should be evaluated for sources of blood loss,
      especially gastrointestinal (eg, colon cancer). Several studies have examined the
      relationship between iron deficiency and hair loss. Almost all have addressed
      women exclusively and have focused on noncicatricial hair loss. Some suggest that
      iron deficiency may be related to alopecia areata, androgenetic alopecia, telogen
      effluvium, and diffuse hair loss, while others do not. Currently, there is
      insufficient evidence to recommend universal screening for iron deficiency in
      patients with hair loss. In addition, there is insufficient evidence to recommend
      giving iron supplementation therapy to patients with hair loss and iron
      deficiency in the absence of iron deficiency anemia. The decision to do either
      should be based on clinical judgment. It is our practice at the Cleveland Clinic
      Foundation to screen male and female patients with both cicatricial and
      noncicatricial hair loss for iron deficiency. Although this practice is not
      evidence based per se, we believe that treatment for hair loss is enhanced when
      iron deficiency, with or without anemia, is treated. Iron deficiency anemia
      should be treated. Treating iron deficiency without anemia is controversial.
      Treatment of nutritional iron deficiency anemia includes adequate dietary intake
      and oral iron supplementation. Excessive iron supplementation can cause iron
      overload and should be avoided, especially in high-risk patients such as those
      with hereditary hemochromatosis. Patients who do not respond to iron replacement
      therapy should undergo additional testing to identify other underlying causes of
      iron deficiency anemia.

PMID- 16635665
TI  - Photoprotection by window glass, automobile glass, and sunglasses.
AB  - In daily activity, much time is spent indoors and in vehicles. Although the
      adverse effect of ultraviolet (UV) radiation is now well recognized and active
      public education programs on photoprotection have been undertaken, the role of
      window glass in photoprotection has been rarely addressed. It has been known for
      some time that window glass filters out UVB and transmits UVA and visible light.
      Recent developments in the glass industry have resulted in glass that provides
      broad UV protection without the historically associated loss of visible light
      transmission. Factors affecting UV-protective properties of glass are glass type,
      glass color, interleave between glass, and glass coating. In this article,
      photoprotection by window glass, automobile glass, and sunglasses is reviewed.

PMID- 16635666
TI  - Hyperimmunoglobulin E syndrome: two cases and a review of the literature.
AB  - Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency associated with
      elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and
      distinctive musculoskeletal features. We report two cases seen at our institution
      and review the current literature. Patient 1 was an 18-month-old African American
      boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He
      had severely eczematous skin, ultimately complicated by eczema herpeticum. After
      treatment of systemic infections with culture-directed antibiotics, a brief
      course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition
      to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15
      year-old Caucasian boy with long-standing HIES. He has been maintained on a
      regimen of interferon gamma injections given 3 times weekly and monthly
      intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics,
      and low-dose fluconazole. He has occasional episodes of cold abscesses and
      sinusitis, but has had excellent control since institution of this regimen and
      has not experienced any adverse effects.

PMID- 16635667
TI  - Intramuscular triamcinolone.

PMID- 16635668
TI  - Large congenital melanocytic nevi, risk of cutaneous melanoma, and prophylactic
      surgery.

PMID- 16635670
TI  - Management of large congenital melanocytic nevi: art versus science.

PMID- 16635671
TI  - Medical pearl: subungual hematoma: a simple and quick method for diagnosis.

PMID- 16635672
TI  - Surgical pearl: simple method for controlling surgical sharps.

PMID- 16635673
TI  - A pilot trial of treprostinil for the treatment and prevention of digital ulcers
      in patients with systemic sclerosis.
AB  - We performed a pilot trial of subcutaneous treprostinil for the treatment of
      digital ulcers in scleroderma. Of the 5 patients completing therapy, ulcer size
      significantly decreased and no new ulcers occurred on continuous therapy.
      Although effective, the high rate of injection site reactions may limit the
      utility of this therapy.

PMID- 16635674
TI  - Prolonged survival of angiosarcoma on the nose: a report of 3 cases.
AB  - The nose is a rare site for presentation of angiosarcoma. Although this
      presentation if difficult to study because of its rarity, previous authors have
      suggested improved survival in patients with angiosarcoma on the nose compared
      with other anatomic sites. If true, improved survival may be a result of early
      detection, small tumor size at time of presentation, and increased likelihood of
      combined surgery and radiation treatment. We report the cases of 3 patients who
      presented with nasal angiosarcoma and then survived 7, 7, and 4 years to date.

PMID- 16635675
TI  - African hair length: the picture is clearer.
AB  - Three subjects with virgin African hair combed daily had surprisingly short hair
      length measurements of 40.1 +/- 14 mm, 60 +/- 10 mm, and 69 +/- 20 mm at 6
      months, 1 year, and 3 years after a haircut, respectively. This observation
      raises the possibility that combing African hair on a daily basis may result in
      the equivalent of a daily haircut in some people. This observation is based on
      few participants and will require confirmation in population studies.

PMID- 16635676
TI  - Epidermolysis bullosa acquisita occurring in 2 patients with hepatitis C.
AB  - We report 2 patients with documented chronic hepatitis C infection and
      epidermolysis bullosa acquisita (EBA). Both patients clinically represent classic
      EBA, exhibiting skin fragility and blistering occurring both spontaneously and
      secondary to trauma, which heal with milia and scar formation. EBA often is a
      disease of altered immune status and debility. Further work is necessary to show
      whether hepatitis C plays a causative role in EBA in these 2 patients and in
      general.

PMID- 16635677
TI  - Treatment of refractory subacute cutaneous lupus erythematosus with efalizumab.
AB  - We report the case of a 47-year-old woman who first presented with erythematous
      plaques on the upper portion of her right arm, which developed into an annular
      eruption involving the face, upper portion of the trunk, and limbs in a
      predominantly photosensitive distribution. Findings from histopathologic
      evaluation of a lesion from her arm were consistent with the clinical diagnosis
      of SCLE. After years of unsuccessful treatment with conventional medications for
      SCLE, she began therapy with efalizumab and experienced dramatic improvement in
      her cutaneous lesions after 6 weeks.

PMID- 16635678
TI  - Presence of perineuritis in a case of papular purpuric gloves and socks syndrome
      associated with mononeuritis multiplex attributable to B19 parvovirus.
AB  - A previously healthy 16-year-old boy developed papular purpuric gloves and socks
      syndrome concomitant with mononeuritis multiplex attributable to acute infection
      with parvovirus B19. A cutaneous biopsy showed lymphocytic lichenoid vasculitis
      and perineuritis. We discuss the relevance of these pathologic findings, and we
      suggest a correlation with the patient's neurologic condition. This case
      illustrates the difficulties in differentiating dysesthesia accompanying
      cutaneous manifestations of exanthem from neurologic disease on the basis of the
      clinical appearance alone.

PMID- 16635679
TI  - Aquagenic syringeal acrokeratoderma: report of a case with histologic findings.
AB  - Aquagenic syringeal acrokeratoderma is a rare acquired condition characterized by
      painful symmetric swelling and hypopigmentation of the palms and lateral fingers,
      which develops after brief exposure to water. Histopathologic examination
      suggests that an aberration in the eccrine sweat gland apparatus may be the
      underlying cause of this condition. The "hand-in-the-bucket sign," in which
      patients arrive in their physician's office with their hand in a bucket of water
      to more readily demonstrate their lesions, is such a common presentation that it
      almost can be regarded as pathognomonic. All 12 cases reported to date have been
      in young females. We report a case of aquagenic syringeal acrokeratoderma in a
      male with unique histologic findings.

PMID- 16635680
TI  - Iron deficiency and hair loss: the jury is still out.

PMID- 16635681
TI  - Treatment of eyelid lesion of angiosarcoma with facial artery recombinant
      interleukin-2 (rIL-2) injection.

PMID- 16635682
TI  - Circumscribed palmar hypokeratosis induced by papilloma virus type 4.

PMID- 16635683
TI  - Dermoscopy for diagnosis and treatment monitoring of pediculosis capitis.

PMID- 16635684
TI  - Adult cutaneous Langerhans cell histiocytosis responsive to topical imiquimod.

PMID- 16635685
TI  - Fever, eosinophilia, and a rash.

PMID- 16635686
TI  - A pediatric case of nephrogenic fibrosing dermopathy: improvement after
      combination therapy.

PMID- 16635687
TI  - Adenocarcinoma of the lung metastatic to the skull presenting as a scalp cyst.

PMID- 16635688
TI  - Hat-wearing patterns in persons attending baseball games.

PMID- 16635689
TI  - Plasma beta-endorphin levels in frequent and infrequent tanners before and after
      ultraviolet and non-ultraviolet stimuli.

PMID- 16635690
TI  - Implications of botulinum toxin injection of the brow.

PMID- 16635691
TI  - Truncal location of hemangioendotheliomas may indicate potentially more serious
      involvement with resulting Kasabach-Merritt syndrome than size determinant alone.

PMID- 16635692
TI  - Vitamin D: the sun as a source?

PMID- 16635693
TI  - Long-pulsed neodymium:yttrium-aluminum-garnet laser treatment for port wine
      stains.

PMID- 16635694
TI  - A comparison of levalbuterol with racemic albuterol in the treatment of acute
      severe asthma exacerbations in adults.
AB  - This multicenter, randomized, double-blind trial compared nebulized levalbuterol
      (Lev) and racemic albuterol (Rac) in the treatment of acute asthma. METHODS:
      Adults with acute asthma exacerbations (FEV(1) 20%-55% predicted) received
      prednisone and either Lev (1.25 mg, n = 315) or Rac (2.5 mg, n = 312). Nebulized
      treatments were administered every 20 minutes in the first hour, then every 40
      minutes for 3 additional doses, then as necessary for up to 24 hours. The primary
      end point was time to meet discharge criteria. Secondary end points included
      changes in lung function and hospitalization rates. A subset of 160 patients had
      plasma (S)-albuterol concentrations determined at study entry. RESULTS: Time to
      meet discharge criteria did not differ between the 2 treatments. FEV(1)
      improvement was greater following Lev compared with Rac, both after dose 1 and
      cumulatively over the entire treatment period (dose 1 in intent to treat [ITT]
      group: Lev 0.50 +/- 0.43 L, Rac 0.43 +/- 0.37 L; P = .02), particularly among the
      60% of patients not on recent steroid therapy (dose 1: Lev 0.58 +/- 0.47 L, Rac
      0.44 +/- 0.37 L; P < .01), and patients whose entry (S)-albuterol concentrations
      were in the highest quartile of those measured. A small and similar proportion of
      Lev-treated (7.0%) and Rac-treated (9.3%) patients required hospitalization (P =
      .28). Among patients not on steroids, fewer Lev- than Rac-treated patients
      required admission (3.8% vs 9.3%, P = .03), as was also the case for patients
      with high plasma (S)-albuterol concentrations. Asthma relapses (5% in 30 days)
      were lower than in previous reports and did not differ between groups.
      CONCLUSIONS: This study suggests that early, regular nebulized beta(2)-agonist
      and systemic corticosteroid therapy may reduce hospitalization and relapse rates
      in patients with acute severe asthma. Lev was well tolerated and compared
      favorably with Rac in improving airway function, particularly in those who were
      not on inhaled or oral corticosteroids and in those who had high plasma (S)
      albuterol concentrations at presentation.

PMID- 16635695
TI  - Utility of thrombocytopenia as a marker for heparin allergy in adult ED patients.
AB  - INTRODUCTION: Up to 5% of patients who receive heparin develop heparin allergy
      (HA), manifested by the presence of heparin antibodies (HAb) and/or the clinical
      syndrome of heparin-induced thrombocytopenia. As many as 10% of patients with HA
      develop serious thrombotic complications when reexposed to heparin. Heparin is
      often given empirically to emergency department (ED) patients, some of whom have
      been recently hospitalized and are at risk for HA/heparin-induced
      thrombocytopenia. Emergency department physicians should have a rapid means of
      determining which patients are at risk for heparin sensitivity. The prevalence of
      HA among ED patients is unknown; most are asymptomatic and unaware, and there is
      no bedside test available. OBJECTIVES: This study was designed to assess the
      prevalence of HA or thrombocytopenia in ED patients and to determine whether
      thrombocytopenia could serve as a useful marker for HA. METHODS: This was a
      prospective, observational study, done during the spring of 2004 in an 80000
      adult visit inner-city ED. A convenience sample of 115 adult patients undergoing
      venipuncture had a blood specimen analyzed for platelet count using standard
      laboratory methods. The same blood sample was tested for the presence of
      antiheparin antibodies using an enzyme-linked immunosorbent assay test. RESULTS:
      Of 115 patients, 12 (10.4%; 95% CI, 6.1%-17.4%) had thrombocytopenia (platelets
      <150000). Six (5.2%; 95% CI, 2.5%-10.9%) had antiheparin antibodies. There was no
      overlap between the 2 groups of patients. CONCLUSIONS: (1) Thrombocytopenia
      occurs in 10% of a sample of 115 adult ED patients undergoing venipuncture in an
      inner-city ED. (2) Heparin allergy was present in 5% of patients in the same
      cohort. (3) Thrombocytopenia is neither sensitive nor specific as a marker for HA
      in ED patients. Heparin-allergic patients are at risk if given heparin; a method
      of rapid detection of patients with HA should be identified.

PMID- 16635696
TI  - An evaluation of emergency physician selection of observation unit patients.
AB  - OBJECTIVE: Appropriate patient selection is critical for maximal observation unit
      (OU) effectiveness. We hypothesized emergency physicians underuse the OU for
      admitted patients and overuse the OU for patients who would otherwise be
      discharged. METHODS: Treating emergency physicians were asked about patient
      suitability for admission to an OU at a busy, urban, academic emergency
      department (ED) as part of a prospective cohort study of ED patients who were
      admitted or had an ED length of stay exceeding 4 hours. The OU was closed for
      renovation during the 2-month study, so physician opinion could be compared with
      patient course in the absence of observation services. Two blinded emergency
      physicians reviewed charts using structured forms and explicit definitions to
      determine actual patient course. Hospitalized patients were considered potential
      OU candidates according to a priori criteria: (1) hospital length of stay less
      than 48 hours, (2) no procedure or diagnosis requiring hospitalization, and (3)
      no death. RESULTS: Of 1747 enrolled patients, 131 were excluded with incomplete
      data. Median age was 45 years. Patients were 40% white and 48% men. Emergency
      physicians identified 363 (23%) patients as observation candidates. Of these, 182
      (50%) were actually discharged directly. The remaining 181 (50%) were
      hospitalized; 101 (56%) were observation candidates based on chart review. Of 799
      admitted patients not selected for observation, 232 (29%) were suitable for
      observation by chart review. CONCLUSIONS: Selection of patients for observation
      was suboptimal; emergency physicians routinely identified patients as OU
      candidates who were not ultimately admitted, and they missed many admitted
      patients who might have been appropriate OU candidates. Both over- and underuse
      should be addressed to maximize the effectiveness of OUs.

PMID- 16635697
TI  - ED predictors of upper gastrointestinal tract bleeding in patients without
      hematemesis.
AB  - OBJECTIVES: In patients with gastrointestinal (GI) tract bleeding, the bleeding
      source is uncertain in the absence of hematemesis. We sought to identify clinical
      variables predictive of an upper GI bleeding source. METHODS: This retrospective
      cohort study involved patients admitted via the ED for GI tract bleeding without
      hematemesis, who underwent confirmatory testing. We used logistic regression
      analysis to identify clinical variables independently associated with an upper GI
      source. RESULTS: Among 325 patients, odds ratios for the strongest predictors
      were as follows: black stool, 16.6 (95% confidence interval [CI], 7.7-35.7); age
      less than 50 years, 8.4 (95% CI, 3.2-22.1); and blood urea nitrogen/creatinine
      ratio 30 or greater, 10.0 (95% CI, 4.0-25.6). Seven (5%) of 151 with none of
      these factors had an upper GI tract bleed, versus 63 (93%) of 68 with 2 or 3
      factors. CONCLUSION: Black stool, age less than 50 years, and blood urea
      nitrogen/creatinine ratio of 30 or greater independently predict an upper GI
      tract bleeding source.

PMID- 16635698
TI  - Efficacy of fentanyl analgesia for trauma in critical care transport.
AB  - INTRODUCTION: Pain relief is one of the most important interventions for out-of
      hospital patient care providers. This paper documents the need for and benefits
      from the administration of fentanyl to trauma patients during critical care
      transport. METHODS: We underwent a retrospective review of the transport charts
      of 100 trauma patients who received fentanyl analgesia during transport and who
      were able to use a numeric response scale to rate their pain from 0 to 10.
      RESULTS: Mean initial pain report was 7.6 +/- 2.2 units, relieved to 3.7 +/- 2.8
      units by a mean total fentanyl dose of 1.6 +/- 0.8 microg/kg (P < .001). Neither
      initial pain level nor pain relief differed between male and female patients, but
      did differ between patients originating at the site of injury and those
      transferred between hospitals. Fentanyl dose correlated poorly with the magnitude
      of pain relief (r = 0.22), but a dose greater than 2 microg/kg provided more
      relief than lower doses (5.1 +/- 2.1 vs 3.6 +/- 2.4, P < .02). CONCLUSION:
      Fentanyl analgesia from these critical care transport teams provided significant
      pain relief to trauma patients. Pain reduction was greater for patients who
      received more than 2.0 microg/kg of fentanyl.

PMID- 16635699
TI  - Incessant ventricular tachycardia acutely controlled with intracoronary injection
      of radiographic contrast media.
AB  - Management of patients with incessant monomorphic ventricular tachycardia is
      challenging. We report on 2 patients who had incessant ventricular tachycardia
      despite emergency treatment with antiarrhythmic drugs and repeated electrical
      cardioversions. In both cases, the arrhythmia was acutely terminated with
      intracoronary administration of radiographic contrast media, allowing hemodynamic
      stabilization. No tachycardia recurrences occurred.

PMID- 16635700
TI  - Ultrasound-guided interscalene block for shoulder dislocation reduction in the
      ED.
AB  - Shoulder dislocations are often associated with significant pain, and many
      emergency physicians choose conscious sedation to achieve reduction. Concerns
      about oxygenation, airway protection, and aspiration may make some patients poor
      candidates for conscious sedation. Ideally, complete pain control and muscle
      relaxation could be achieved without airway compromise. Interscalene nerve blocks
      are routinely used for shoulder surgery in the operating suite. The equipment
      required to locate the nerve plexus blindly is typically not available in the ED
      setting. Recent work has shown that ultrasound guidance is ideal for the
      interscalene block and would make it possible in the ED. We present 4 cases of
      patients receiving ultrasound-guided interscalene blocks for pain control and
      muscle relaxation during shoulder reduction. Complete pain control, muscle
      relaxation, and joint reduction were achieved in each case.

PMID- 16635701
TI  - Pediatric hyperglycemic hyperosmolar syndrome: diagnostic difficulties and high
      mortality rate.
AB  - Childhood obesity has become a pandemic health care problem. A complication of
      childhood obesity is type 2 diabetes mellitus which has increased 10-fold in the
      past 20 years. A serious complication of type 2 diabetes mellitus is
      hyperglycemic hyperosmolar syndrome (HHS). The following case is an obese
      adolescent boy with a newly diagnosed HHS. The demographic and clinical
      characteristics of our case and those of 17 other cases from recently published
      small case series are presented. Of the 18 cases, there were 13 deaths (72%). The
      purpose of this report and literature review is to emphasize the importance of
      early diagnoses and treatment of pediatric HHS.

PMID- 16635702
TI  - Utility of a novel quantitative handheld microstream capnometer during transport
      of critically ill children.
AB  - OBJECTIVE: Critically ill children often require endotracheal intubation before
      and during interhospital transport. Accurate placement and maintenance of the
      endotracheal tube (ETT) is crucial. The new Pediatric Advanced Life Support
      guidelines require confirmation of proper ETT position immediately after
      intubation and during transport by capnography or end-tidal carbon dioxide
      (ETco(2)) detection in all children with a perfusing rhythm. Currently, there are
      no practical alternatives for monitoring ETco(2) during pediatric transport.
      Therefore, we evaluated NPB-75, a quantitative handheld microstream capnometer,
      during transport of children to our urban children's hospital. METHODS:
      Consecutive intubated patients who were transported by ground ambulance or
      rotorcraft were prospectively enrolled into the study. Physical examination,
      colorimetric CO(2) detector, pulse oximetry, and, in most cases, chest radiograph
      confirmed the initial ETT position. The capnometer was then attached, and ETco(2)
      readings were obtained before and during transport by nurses or respiratory
      therapists who also completed a brief questionnaire regarding the monitor
      immediately after every transport. A numerical light-emitting diode display and
      graphic liquid crystal display waveform confirmed the presence of ETco(2). An
      audiovisual alarm alerted the transport personnel when CO(2) was not detected.
      RESULTS: Fifty patients comprised the study group, ages birth to 15.3 years
      (median, 4 months) and weighing 1.63 to 70 kg (median, 5.25 kg). Nineteen
      patients were transported by ground ambulance and 31 by rotorcraft. The
      capnometer confirmed ETT position during transport in all patients. The
      audiovisual alarm of the capnometer immediately detected a ventilator
      disconnection from the ETT during one air transport. The size of the device was
      evaluated as "just right" in 37 of 50 transports, "easy to secure" in 46 of 50,
      and "useful" in all 50 transports. There were no false-negative readings,
      occlusion, or kinking of tubing during transport. NPB-75 was specifically useful
      for setting optimal ventilatory support in 2 patients with raised intracranial
      pressure who required controlled ventilation. Furthermore, it confirmed adequate
      ventilation when the ventilator falsely detected a low respiratory rate in a
      newborn with a congenital heart disease for whom pulse oximetry was unreliable.
      The ETco(2) waveform detected air trapping in 2 ventilated asthmatic patients.
      CONCLUSIONS: This lightweight microstream capnometer with a 4-hour battery life
      and audiovisual alarms functioned well in the prehospital setting. It provided
      both quantitative and graphic real-time detection of ETco(2) in intubated
      patients, which was of critical importance for the optimal management of patients
      during transport.

PMID- 16635703
TI  - Self-inflicted splenic injury in snowboarders: postural analysis of forward falls
      of 10 consecutive patients.
AB  - Splenic injuries are often caused when snowboarders thrust their abdomens with
      their own left elbows after falling and hitting the ground. We report 10
      snowboarders who suffered a splenic injury by accidentally thrusting their own
      elbow against their abdomen upon falling to the ground. Clinical presentation,
      postural analysis, and treatment are described. In an attempt to break the force
      while falling, snowboarders assumed 1 of 2 defensive postures that subsequently
      induced splenic injury: falling with an outstretched hand or falling with folded
      arms placed closely to the chest, that is, the fetal tuck posture. Snowboarders
      who fell in the outstretched hand posture developed more severe symptoms than
      those who fell in the fetal tuck posture. Herein, we discuss the mechanisms of
      such snowboarding-related splenic injury in detail and provide a review of the
      literature.

PMID- 16635704
TI  - Referent d-dimer enzyme-linked immunosorbent assay testing is of limited value in
      the exclusion of thromboembolic disease: result of a practical study in an ED.
AB  - OBJECTIVE: The aim of this study was to assess in clinical practice the accuracy
      of a referent d-dimer enzyme-linked immunosorbent assay for the exclusion of
      venous thromboembolic disease (VTED). PATIENTS AND METHODS: An observational
      prospective study took place in an emergency department; 205 consecutive
      outpatients suspected of having VTED were included. Blood samples were collected
      at admission for VIDAS DD measurement. Venous thromboembolic disease was
      confirmed by standard clinical imaging. All patients were followed up at 3
      months. RESULTS: Venous thromboembolic disease was confirmed in 57 patients
      (28%). The sensitivity and negative predictive value of a DD assay lower than 500
      ng/mL were 78% (95% confidence interval = 67%-87%) and 84% (95% confidence
      interval = 73%-90%), respectively. Twelve patients had a false-negative DD with
      one or more of the following: (a) symptoms reported for more than 15 days (n =
      2), (b) prior anticoagulation (n = 3), (c) distal VTED (n = 5), or (d) high
      clinical probability (n = 3). CONCLUSION: In our cohort of patients, DD was less
      accurate than previously reported, with an upper estimate of the sensitivity of
      only 87%.

PMID- 16635705
TI  - ED patients with heart failure: identification of an observational unit
      appropriate cohort.
AB  - OBJECTIVE: To identify factors that define a low-risk cohort of patients with
      acute decompensated heart failure who are suitable for management in an
      observation unit. METHODS: Prospective convenience sample of 538 patients who
      presented to an ED with a diagnosis of congestive heart failure. Observation unit
      appropriate was defined as a length of stay less than 24 hours and no adverse
      events (myocardial infarction, death, arrhythmia, or rehospitalization) during
      the 30-day follow-up period. RESULTS: Study criteria were met by 499 patients
      (mean age, 61 +/- 15 years), and 234 (47%) were women. Of these, 133 (27%) met
      the criteria for observation unit appropriateness. Independent predictors were
      systolic blood pressure of greater than 160 (odds ratio, 1.8; 95% confidence
      interval, 1.15-2.7) and normal troponin I (odds ratio, 14.7; 95% confidence
      interval, 1.9-105). CONCLUSION: Initial blood pressure and troponin I can help
      identify patients with congestive heart failure at low risk for prolonged
      hospitalization and adverse events and who are reasonable candidates for
      observation unit management.

PMID- 16635706
TI  - Patient follow-up after negative lower extremity bedside ultrasound for deep
      venous thrombosis in the ED.
AB  - OBJECTIVES: To evaluate the rate of patient compliance with follow-up ultrasound
      (US) examinations 5 to 7 days after emergency physician EP performed US exams to
      rule out lower extremity deep venous thrombosis (DVT) in the ED. METHODS: This
      was a prospective observational study at a level I ED with a residency program,
      US training program, and an annual census of 75000. Hospital-based emergency US
      credentialing is available and derived from American College of Emergency
      Physicians guidelines. Five US-credentialed emergency physicians participated in
      the study. All patients who received negative lower extremity DVT US exams were
      eligible. All higher risk patients were given verbal and written instructions and
      provided with prescriptions to have a follow-up US examination 5 to 7 days after
      their examination in the ED. Those classified as "low risk" based on Wells
      criteria were excluded. After 3 months, patients were contacted via telephone and
      asked questions regarding their follow-up US examinations, reasons for not
      following up, continued symptoms, and thromboembolic events. Statistical methods
      included descriptive statistics. RESULTS: One hundred fifty-nine patients were
      eligible for enrollment during the 10-month study period. Eighty-five patients
      (54%) fell into the higher risk category of these; 54 (64%) were contacted
      successfully. Fifteen (28%) of the patients contacted had obtained a follow-up US
      exam. Of the 39 who did not follow-up, 29% were told by their physician that a
      follow-up US was unnecessary, 21% forgot to follow-up, 8% did not follow-up for
      financial reasons, 16% felt better, 5% could not arrange a study, 21% were
      unsure. One patient died from sepsis before a follow-up scan. Two patients were
      diagnosed with DVT, one at 7 days follow-up and the other 9 months later (this
      particular patient had their 7-day scan cancelled by their primary care
      physician). CONCLUSION: Patients who were instructed to obtain follow-up lower
      extremity US examinations to rule out propagation of unseen, distal DVTs did so
      at a very low rate in our study. One of the largest impediments in our study
      population was a patients' primary care physician who may not understand the need
      for a follow-up US examination.

PMID- 16635707
TI  - Managing acute lower respiratory tract infections in an era of antibacterial
      resistance.
AB  - Respiratory tract infections account for more than 116 million office visits and
      an estimated 3 million visits to hospital EDs annually. Patients presenting at
      EDs with symptoms suggestive of lower respiratory tract infections of suspected
      bacterial etiology are often severely ill, thus requiring a rapid presumptive
      diagnosis and empiric antimicrobial treatment. Traditionally, clinicians have
      relied on beta-lactam or macrolide antibiotics to manage community-acquired lower
      respiratory tract infections. However, the emerging resistance of Streptococcus
      pneumoniae to beta-lactams and/or macrolides may affect the clinical efficacy of
      these agents. Inappropriate use of antibiotics and use of agents with an overly
      broad spectrum of antimicrobial activity have contributed to the emergence of
      antibiotic resistance. When treating respiratory infections, clinicians need to
      prescribe antimicrobial agents only for those individuals with infections of
      suspected bacterial etiology; to select agents with a targeted spectrum of
      activity that ensures coverage against typical S pneumoniae, Haemophilus
      influenzae, and Moraxella catarrhalis strains, including antibiotic-resistant
      strains and atypical pathogens; and to consider agents with specific chemical
      properties that limit the development of antimicrobial resistance and that
      achieve concentrations at sites of infection that exceed those required for
      bactericidal activity. Newer classes of antimicrobial agents, such as the
      oxazolidinones and ketolides, will likely play a significant role in this era of
      antimicrobial resistance.

PMID- 16635708
TI  - Intranasal midazolam therapy for pediatric status epilepticus.
AB  - Prolonged seizure activity in a child is a frightening experience for families as
      well as care providers. Because duration of seizure activity impacts morbidity
      and mortality, effective methods for seizure control should be instituted as soon
      as possible, preferably at home. Unfortunately, parenteral methods of medication
      delivery are not available to most caregivers and rectal diazepam, the most
      commonly used home therapy, is expensive and often ineffective. This brief review
      article examines recent research suggesting that there is a better way to treat
      pediatric seizures in situations where no intravenous access is immediately
      available. Intranasal midazolam, which delivers antiepileptic medication directly
      to the blood and cerebrospinal fluid via the nasal mucosa, is safe, inexpensive,
      easy to learn by parents and paramedics, and provides better seizure control than
      rectal diazepam.

PMID- 16635709
TI  - Spontaneous urinary extravasation: an overlooked cause of acute abdomen in ED.

PMID- 16635710
TI  - What happens when a person eats the entire "meals ready to eat?".

PMID- 16635711
TI  - Emphysematous pyelonephritis: presenting with pneumomediastinum.

PMID- 16635712
TI  - Spinal cord infarction after weight lifting.

PMID- 16635713
TI  - Global electrocardiographic changes accompanying acute presentation of 3-vessel
      coronary disease.

PMID- 16635714
TI  - A satisfactory recovery after emergency direct cardiac massage in type A acute
      aortic dissection with cardiac arrest.

PMID- 16635715
TI  - Mixed venous oxygen saturation monitoring in calcium channel blocker poisoning:
      tissue hypoxia avoidance despite hypotension.

PMID- 16635716
TI  - A primary respiratory vs cardiac problem in a child--pediatric myocarditis.

PMID- 16635717
TI  - Apparent wide complex tachycardia after ventricular fibrillation cardiac arrest
      in patients with ST-segment elevation myocardial infarction.

PMID- 16635718
TI  - Case report of combined olecranon fracture and lateral condyle fracture.

PMID- 16635719
TI  - A patient with sudden-onset shortness of breath.

PMID- 16635720
TI  - Violent abdominal pain: severe Legionella pneumophila lung infection with acute
      pancreatitis.

PMID- 16635721
TI  - Duodenal stump perforation after an elbow strike in a basketball player.

PMID- 16635722
TI  - Unilateral pulmonary edema related to massive mitral insufficiency.

PMID- 16635723
TI  - Acute pericarditis: a rare complication of Graves' thyrotoxicosis?

PMID- 16635724
TI  - Acute cardiac ischemia time-insensitive predictive instrument predicts exercise
      treadmill test results in the chest pain unit.

PMID- 16635725
TI  - Computed tomographic image of Fahr disease mistaken for acute hemorrhagic
      cerebrovascular accident.

PMID- 16635726
TI  - Aortic dissection presenting with atrial fibrillation.

PMID- 16635727
TI  - Hemiparesis following sunbathing.

PMID- 16635728
TI  - Rapid identification of surreptitious brodifacoum poisoning by analysis of
      vitamin K-dependent factor activity.

PMID- 16635729
TI  - Rupture of the renal pelvis complicating a renal colic: report of a case.

PMID- 16635730
TI  - Isolated superior mesenteric artery dissection in a patient without risk factors
      or aortic dissection.

PMID- 16635731
TI  - Reply to "Insufficient evidence that agitation is common in gamma-hydroxybutyrate
      (GHB) toxicity," submitted in response to our original article entitled,
      "Agitation is common in gamma-hydroxybutyrate toxicity," published in AJEM, May
      2005.

PMID- 16635732
TI  - Hypothermic cardiac arrest: an update.

PMID- 16635733
TI  - Delays in antibiotic administration associated with chest X-ray negative and
      computed tomographic scan positive for pneumonia.

PMID- 16635734
TI  - No debate on the minimal decline in pain intensity that patients can discern.

PMID- 16635735
TI  - Serious pancytopenia from methotrexate treatment of psoriatic arthritis.

PMID- 16635736
TI  - Lethargic children: a term misused in pediatric emergency medicine.

PMID- 16635737
TI  - Identification of equol producers in a Japanese population by high-performance
      liquid chromatography with coulometric array for determining serum isoflavones.
AB  - Using a method of high-performance liquid chromatography (HPLC) with coulometric
      array, we measured isoflavone levels in sera from seven volunteers before and
      after three days of ingesting Soyaflavone E (an isoflavones powder) and from 129
      female farmers (Japanese Multiple Environmental Toxicants Study; JMETS). Results
      showed that the serum isoflavone concentrations rose dramatically after three
      days of ingesting Soyaflavone E in all subjects except for the serum equol
      concentrations in two subjects. The geometric mean concentrations of daidzein,
      genistein, and equol in the serum of 129 Japanese women were 25.0 ng/ml of
      daidzein, 94.1 ng/ml of genistein, and 9.6 ng/ml of equol. Interestingly, there
      existed two dominant groups in terms of serum equol concentrations in an
      independent manner of soy-derived product intake among the study participants.

PMID- 16635738
TI  - Structure-activity relations of inhibitory effects of various flavonoids on
      lipopolysaccharide-induced prostaglandin E2 production in rat peritoneal
      macrophages: comparison between subclasses of flavonoids.
AB  - A study of the structure-activity relations of the inhibitory effect of
      flavonoids on lipopolysaccharide (LPS)-induced prostaglandin production was
      carried out via a comparative examination of 39 flavonoids and related compounds.
      A comparison of the subclasses showed that flavones were most effective, followed
      by flavanones. Flavonols were less effective than those two groups. These results
      suggest that the C2-C3 double-bond and 4-oxo functional group of the C-ring are
      important factors for the high inhibition activities. Flavonoids showed the
      strongest inhibitory effect on the expression of Cox-2 protein. These results
      help to explain part of the reason for the pharmacological efficacy of flavonoids
      as anti-inflammatory compounds.

PMID- 16635739
TI  - The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of
      warfarin in rats.
AB  - Significant pharmacokinetic/pharmacodynamic interactions between various herbal
      products and warfarin have recently been reported. The aim of this study was to
      determine whether concomitant treatment of rats with Kan Jang (a standardized
      fixed combination of extracts from Andrographis paniculata and Eleutherococcus
      senticosus) and warfarin would lead to an alteration in the pharmacological
      effects of warfarin. Each day for 5 days a group of animals was treated orally
      with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active
      principle andrographolide (a daily dose some 17-fold higher than that recommended
      for humans): the control group received similar treatment with appropriate
      volumes of water only. Sixty minutes after the final daily administration of Kan
      Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each
      animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2,
      4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples
      taken. The concentration of warfarin in blood plasma was measured by capillary
      electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with
      simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in
      blood plasma was measured using thromboplastin reagent. The concomitant
      application of Kan Jang and warfarin did not produce significant effects on the
      pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.

PMID- 16635740
TI  - Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6
      (IL-6) and vascular endothelial growth factor (VEGF) production.
AB  - Recent studies have indicated that cytokines can enhance immunogenicity and
      promote tumor regression. However, the means for modulating cytokine production
      are not yet fully investigated. In this study we report the effects of a herbal
      melanin, extracted from Nigella sativa L., on the production of three cytokines
      [tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular
      endothelial growth factor (VEGF)], by human monocytes, total peripheral blood
      mononuclear cells (PBMC) and THP-1 cell line. Cells were treated with variable
      concentrations of melanin and the expression of TNF-alpha, IL-6 and VEGF mRNA in
      cell lysates and secretion of proteins in the supernatants were detected by RT
      PCR and ELISA. Melanin induced TNF-alpha, IL-6 and VEGF mRNA expression by the
      monocytes, PBMC and THP-1 cell line. On the protein level, melanin significantly
      induced TNF-alpha and IL-6 protein production and inhibited VEGF production by
      monocytes and PBMC. In the THP-1 cell line melanin induced production of all
      three cytokine proteins. These observations raise the prospects of using N.
      sativa L. melanin for treatment of diseases associated with imbalanced cytokine
      production and for enhancing cancer and other immunotherapies.

PMID- 16635741
TI  - Selective inhibition of vascular smooth muscle cell proliferation by coptisine
      isolated from Coptis rhizoma, one of the crude drugs composing Kampo medicines
      Unsei-in.
AB  - Acceleration of vascular smooth muscle cell (VSMC) proliferation is closely
      linked to the pathogenesis of vascular diseases. We, therefore, focused on
      traditional Japanese herbal medicines (Kampo medicines) used to ameliorate the
      impairment of microcirculation or blood stasis and screened them for their
      ability to inhibit rat VSMC proliferation. Among them, Unsei-in was found to
      effectively suppress VSMC proliferation, and Coptis rhizome was the responsible
      constituent crude drug. The extract of Coptis rhizome inhibited VSMC
      proliferation with the GI(50) value of 4.4 microg/ml, which was much lower than
      those against the proliferation of 3Y1, dRLh-84, B16, and HeLa cells. The Coptis
      rhizome extract inhibited the progression of VSMC arrested at G(0)/G(1) phase
      from G(0)/G(1) to S phase, but not that of 3Y1 cells. Biological assay-guided
      fractionation revealed that an alkaloid of Coptis rhizome, coptisine, was the
      active ingredient in selectively preventing VSMC proliferation with GI(50) of 3.3
      microM (1.2 microg/ml). When the structurally-related isoquinoline alkaloids of
      protoberberine class were studied for their inhibitory activities, berberine
      decreased the VSMC proliferation with GI(50) of 95.1 microM (35.4 microg/ml),
      about 30 times higher concentration than coptisine, while palmatine failed to
      show any activity. This study provides evidence that coptisine, an ingredient of
      Unsei-in, prevents VSMC proliferation selectively at lower concentrations
      compared with various cells or other structurally related alkaloids.

PMID- 16635742
TI  - Screening of antiradical and antioxidant activity of monodesmosides and crude
      extract from Leontice smirnowii tuber.
AB  - Leontice smirnowii is a member of the Berberidaceae family. In the current study
      we investigated the possible antiradical and antioxidant activity of the
      monodesmosides (MLS) and crude extract (CELS) of Leontice smirnowii using
      different antioxidant tests: 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical
      scavenging, scavenging of superoxide anion radical-generated non-enzymatic
      system, ferric thiocyanate (FTC) method, reducing power, hydrogen peroxide
      scavenging and metal chelating activities. Experiment revealed that MLS and CELS
      have an antioxidant effect concentration-dependently. Total antioxidant activity
      was performed according to FTC method. At the 30mug/ml concentration, the
      inhibition effects of MLS and CELS on peroxidation of linoleic acid emulsion were
      found to be 95.3% and 95.6%, respectively. On the other hand, percentage
      inhibition of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT),
      alpha-tocopherol and trolox were found to be 98.2%, 98.5%, 84.0% and 87.9%
      inhibition of peroxidation of linoleic acid emulsion, respectively, at the same
      concentration. In addition, MLS and CELS had effective DPPH radical scavenging,
      superoxide anion radical scavenging, hydrogen peroxide scavenging, reducing power
      and metal chelating activities. Also, these various antioxidant activities were
      compared with BHA, BHT, alpha-tocopherol and trolox which were accepted as
      references antioxidants.

PMID- 16635743
TI  - Effect of polysaccharides from Opuntia ficus-indica (L.) cladodes on the healing
      of dermal wounds in the rat.
AB  - In traditional medicine extracts of polysaccharide-containing plants are widely
      employed for the treatment of skin and epithelium wounds and of mucous membrane
      irritation. The extracts of Opuntia ficus-indica cladodes are used in folk
      medicine for their antiulcer and wound-healing activities. The present study
      describes the wound-healing potential of two lyophilized polysaccharide extracts
      obtained from O. ficus-indica (L.) cladodes applied on large full-thickness
      wounds in the rat. When topically applied for 6 days, polysaccharides with a
      molecular weight (MW)>10(4)Da from O. ficus-indica cladodes induce a beneficial
      effect on cutaneous repair in this experimental model; in particular the topical
      application of O. ficus-indica extracts on skin lesions accelerates the
      reepithelization and remodelling phases, also by affecting cell-matrix
      interactions and by modulating laminin deposition. Furthermore, the wound-healing
      effect is more marked for polysaccharides with a MW ranging 10(4)-10(6)Da than
      for those with MW>10(6)Da, leading us to suppose that the fine structure of these
      polysaccharides and thus their particular hygroscopic, rheologic and viscoelastic
      properties may be essential for the wound-healing promoter activity observed.

PMID- 16635744
TI  - Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii.
AB  - In the current study, we isolated 10 carbazole alkaloids from the plant species
      Murraya koenigii (Rutaceae), and examined their effects on the growth of the
      human leukemia cell line HL-60. Three carbazole alkaloids, mahanine (6),
      pyrayafoline-D (7) and murrafoline-I (9), showed significant cytotoxicity against
      HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that
      the percentage of apoptotic cells with fragmented nuclei and condensed chromatin
      was increased in a time-dependent manner after treatment with each alkaloid.
      Interestingly, each carbazole alkaloid induced the loss of mitochondrial membrane
      potential. In addition, both caspase-9 and caspase-3 were also time-dependently
      activated upon treatment with the alkaloids. Caspase-9 and caspase-3 inhibitors
      suppressed apoptosis induced by these alkaloids. The results suggest that these
      three alkaloids induced apoptosis in HL-60 cells through activation of the
      caspase-9/caspase-3 pathway, through mitochondrial dysfunction.

PMID- 16635745
TI  - Antitumor and immunostimulating effects of Anoectochilus formosanus Hayata.
AB  - The water extract of Anoectochilus formosanus Hayata showed a potent tumor
      inhibitory activity in BALB/c mice after subcutaneous transplantation of CT-26
      murine colon cancer cells. The tumor-inhibition ratios of mice pre-administered
      with A. formosanus for 2 days before tumor transplantation, and treated further
      for 12 consecutive days, were 55.4% and 58.9% at the oral dose of 50 and 10
      mg/mouse per day, respectively. Even for the tumor-bearing mice, after oral
      administration of the water extract of A. formosanus for 12 consecutive days, the
      tumor inhibition ratios were still 23.8% and 40.5% at doses of 50 and 10
      mg/mouse, respectively. Because the low-concentration water extract of A.
      formosanus does not show direct cytotoxicity in CT-26 tumor cells, we observed
      further that oral administration of the water extract of A. formosanus may
      activate murine immune responses, such as stimulating the proliferation of
      lymphoid tissues and activating the phagocytosis of peritoneal macrophages
      against Staphylococcus aureus. This study suggests that the antitumor activity of
      A. formosanus may be associated with its potent immunostimulating effect. It is
      worth further analyzing the immunomodulating component purified from A.
      formosanus, and evaluating its potential value for the treatment of human
      cancers.

PMID- 16635746
TI  - Role of platelet-derived chemokines (RANTES and ENA-78) after stem cell
      transplantation.
AB  - Stem cell transplantation (SCT) is being used for hematopoietic reconstitution
      following high-dose chemotherapy for malignancy. Some patients seem to have an
      imbalance of the immune response after SCT and cytokines are known to regulate
      this response. Recently, platelets have been shown to contain members of the
      chemokine family, suggesting a role of platelets as inflammatory cells. We
      measured and compared levels of platelet activation markers, chemokines, and
      soluble factors in patients undergoing SCT. IL-8 and GROalpha exhibited a
      significant elevation in the early phase (1 or 2 weeks) after SCT; this trend was
      marked after autologous SCT. Furthermore, these levels significantly and
      positively correlated with the change in G-CSF. In contrast, ENA-78 exhibited a
      significant elevation in the later phase (3 or 4 weeks) after SCT. In addition,
      its level negatively correlated with the change in G-CSF. Soluble CD40 ligand and
      platelet-derived microparticles significantly increased after both auto- and allo
      SCT. In addition, ENA-78 positively correlated with the level of platelet-derived
      microparticles. The increase of RANTES seems to be related to platelet
      activation, since RANTES was in the dynamic phase similar to soluble CD40 ligand
      and platelet-derived microparticles. RANTES exhibited changes similar to IL-6,
      TNFalpha, and soluble IL-2 receptors, which are GVHD markers. Thus, the platelet
      derived chemokines ENA-78 and RANTES exhibited particular changes after SCT. Our
      results suggest that ENA-78 play a role in hematopoietic conditions in which G
      CSF is not involved, and RANTES generation after allo-SCT relates to GVHD.

PMID- 16635747
TI  - Expression level of costimulatory receptor ICOS is critical for determining the
      polarization of helper T cell function.
AB  - We found that inducible costimulator (ICOS)-deficient spleen cells have a defect
      in the ability to induce Th2-mediated chronic graft-versus-host disease (GVHD),
      whereas they were fully capable of inducing Th1-mediated acute GVHD. In contrast,
      CD28-deficient spleen cells induced neither acute nor chronic GVHD. To define the
      mechanisms of how these two CD28 family molecules manifest distinct functions in
      GVHD, the kinetics of their surface expression by donor T cells in two types of
      GVHD were investigated. It was found that expression of ICOS by donor T cells
      dramatically up-regulated after adoptive transfer in both acute and chronic GVHD,
      but in acute GVHD this up-regulation was transient and quickly down-regulated. In
      contrast, donor T cells in chronic GVHD maintained high levels of ICOS expression
      throughout the experiment. These results suggested that ICOS-mediated
      costimulatory signals are predominantly active in Th2-dominant responses.
      Changing patterns of CD28 expression by donor T cell were identical in both GVHD
      as they exhibited slight but sustained up-regulation after transfer, suggesting
      that CD28 provides a costimulatory signal necessary for the initial T cell
      activation, regardless of whether in Th1 or Th2 responses. These results lead us
      to propose that the expression levels of costimulatory receptors are critical for
      determining the polarization of helper T cell function.

PMID- 16635748
TI  - Evidence that FTY720 induces rat thymocyte apoptosis.
AB  - FTY720, a novel immunomodulator with the potential to improve immunosuppressive
      therapy after organ transplantation, is currently under clinical investigation.
      FTY720 drastically decreases blood lymphocytes, especially T cells, accelerating
      lymphocyte homing to secondary lymphoid organs. However, its immunosuppressive
      effects remain unknown. We investigated these effects in rat thymocytes. Rats
      were intramuscularly injected with 10mg/kg/day FTY720 or saline for 7days.
      Thymuses were removed on days 0, 1, 3, 5, 7 and 14 after treatment. Three-color
      analysis was performed with a flow cytofluorometer. Apoptotic nuclei in the
      tissue sections were identified by TUNEL. Genomic DNA was then extracted and
      samples were electrophoresed on 2.0% agarose gel. FTY720 reduced the total number
      of thymocytes and, with time, significantly reduced the percentage of CD4+8+
      TCRalphabeta(negative/low) thymocytes. Light microscopy of thymuses of FTY720
      treated rats revealed obvious reductions in the size of the cortical region.
      TUNEL analysis showed that FTY720 induced thymocyte apoptosis in the cortical
      region. Furthermore, DNA fragmentation was observed in thymocytes treated with
      FTY720, indicating thymocyte apoptosis. FTY720 reduced the number of CD4+8+
      thymocytes before TCRalphabeta expression resulting in impaired thymocyte
      differentiation and maturation. This might be an immunosuppressive effect of
      FTY720.

PMID- 16635749
TI  - Influence of polyclonal anti-thymocyte globulins upon ischemia-reperfusion injury
      in a non-human primate model.
AB  - BACKGROUND: Polyclonal anti-thymocyte globulins (ATGs) are used to induce
      immunosuppression and to treat acute rejection after transplantation. ATGs induce
      apoptosis and in peripheral T-lymphocytes having the potential to inhibit
      leukocyte adhesion. We analysed the influence of three different ATGs upon the
      microvasculature and the different cell-subpopulations after ischemia/reperfusion
      (IRI). MATERIALS AND METHODS: Extremities of cynomolgus monkeys were surgically
      isolated and flushed with Ringer's lactate at 4 degrees C. After 60 min of
      ischemia the limbs were reperfused with matching human blood. ATGs were added to
      the blood 30 min prior to the reperfusion. Four groups were generated: Tecelac
      ATG group, Fresenius(S)-ATG group, Thymoglobulin-ATG group and a control group.
      Blood analyses were performed in blood samples taken after the beginning of the
      reperfusion. Biopsies from muscular tissue were obtained after the experiments.
      RESULTS: The number of circulating leukocytes was lower in the ATG-groups than in
      control. Morpho-cytological analyses showed depletion of peripheral lymphocytes.
      Histological examination showed less tissue damage, reduced presence of fibrin
      and adherent thrombocytes in the ATG-treated groups. Leukocyte infiltration, both
      in muscle and vascular structures, was significantly diminished in the ATG-groups
      in comparison to control. DISCUSSION: Our results show that ATGs have a
      favourable impact on early mechanisms of IRI. ATGs showed a reduction of the
      number of adherent leukocytes and muscle infiltrates suggesting that preoperative
      therapy with ATGs may have an advantageous effect on primary non-function and on
      chronic rejection as well as a positive influence upon IRI.

PMID- 16635750
TI  - FTY720 treatment of kidney transplant patients: a differential effect on B cells,
      naive T cells, memory T cells and NK cells.
AB  - FTY720 alters lymphocyte recirculation and homing by interfering with S1P
      receptors on lymphocytes, possibly in combination with chemokine receptors, and
      induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney
      transplant patients, we analyzed by flow cytometry the effect of FTY on the
      number of NK cells, monocytes, naive (CCR7+) T cells, memory (CCR5+) T cells and
      B cells. Patients treated with 0.5, 2.5 or 5mg FTY/day showed a strong decrease
      in T and B cell numbers. NK cells and monocytes were not affected. FTY reduced
      primarily naive T cells. From the memory T cells (CCR5+), predominantly CD8
      cells, 40-60% remained in the circulation. The majority of the CCR7+ cells
      disappeared from the circulation within 3-6h, while a further reduction was
      achieved later. The more slowly decrease in naive CCR7+ T cell numbers was also
      observed in the group treated with 0.25mg FTY/day. Elispot assays revealed no IL
      4 producing cells and a low frequency of IFN-gamma producing cells. We suggest
      that both CCR7 dependent and independent mechanisms are involved in the depletion
      of T cells from peripheral blood.

PMID- 16635751
TI  - Genetic association of interleukin-1beta and receptor antagonist (IL-1Ra) gene
      polymorphism with allograft function in renal transplant patients.
AB  - Cytokines are known to be important mediators during renal graft outcome. The
      present study was therefore, conducted to determine the impact of IL-1beta and
      its receptor antagonist polymorphism on allograft outcome. We evaluated single
      nucleotide polymorphism (SNPs) in interleukin-1 gene cluster, IL-1beta (promoter
      region -511 and exon-5 +3954) and IL-1Ra (86-bp VNTR) in 136 renal transplant
      recipients and 150 normal healthy controls by polymerase chain restriction based
      (PCR-RFLP) analysis. Recipients were HLA matched and clinically characterized
      including delayed graft function (DGF), rejection episode (RE) and stable graft
      function (SGF). Haplotypes and linkage disequilibrium (LD) were determined using
      SNPAnalyzer software. Significant difference was observed for the frequency
      distribution of the three sites of IL-1 gene among patients and controls
      (p<0.001, 0.022 and <0.001 respectively). When RE and DGF were compared to SGF,
      only IL-1Ra showed significant differences among RE and SGF (p=0.014) and DGF and
      SGF (p=0.020). The presence of 1/2 genotype showed 18 folds risk in RE and 10
      folds in DGF (OR=18.000 and OR=10.667 respectively). The majority of recipients
      with SGF had 1-4 HLA mismatch whereas RE had 5-8 mismatches. Risk for rejection
      increased >6 folds (OR=6.571; p<0.01) for 5-8 mismatches. Haplotypes constructed
      with the combination of three polymorphisms in IL-1 gene cluster showed
      significant difference between RE and SGF group. LD value for IL-1beta (promoter
      region) and IL-1Ra and IL-1beta promoter and exon-5 gene in the control group
      indicated strong association among the variants (D'=0.37, p<0.0001 and D'=0.29,
      p=0.002). Our study demonstrate that genetically determined low production of IL
      1Ra may be a risk factor for RE and DGF and that IL-1beta/IL-1Ra haplotype
      influences the impact of allograft outcome. These findings may significantly abet
      in better perception of the survival of the graft.

PMID- 16635752
TI  - Pregnancy after liver transplantation: report of 8 new cases and review of the
      literature.
AB  - Improved survival and quality of life following liver transplantation are
      associated with an increased frequency of pregnancies in liver-transplanted
      women. We investigated the outcome, complications, and management of those
      pregnancies. We have reviewed the literature and report 8 pregnancies in 6
      transplant recipients. Seven pregnancies were completed at 38+/-2 (mean+/
      standard deviation) weeks. One miscarriage occurred at week 12. Newborns' weight
      averaged 2938+/-156 g. Main complications were preeclampsia (n=1) and reversible
      cholestasis (n=1). Among 285 pregnancies reported in literature, 78+/-20% were
      successful and the main complications were: preeclampsia (26+/-19%), hypertension
      (28+/-19%), reversible liver dysfunction (27+/-21%), cesarean delivery (23+/
      10%), preterm birth (31+/-28%), small for gestational age infants (23+/-10%),
      rejection (10+/-7%). Gestational weeks were 36.7+/-1.3, perinatal mortality was
      4+/-10%, malformation rate 3%. The rates of both abortions and complications
      (preeclampsia and/or hypertension) were inversely related to the time interval
      between transplantation and conception (p<0.05). Abortions occurred more often in
      recipients whose underlying disease was autoimmune cirrhosis than in recipients
      with inherited disorders. Rejection rate was approx. 10%, which appears higher
      than reported in a non-pregnant population after a comparable time interval from
      transplant (2-3%). Up to 28 months after delivery, maternal death was 5.5+/-7%.
      We conclude that: the time intervals between transplantation and conception as
      well as the original cause of liver failure influence the outcome and
      complications of pregnancies in liver recipients. However, neonatal survival is
      high, while malformations are relatively rare.

PMID- 16635753
TI  - Polymorphism of the renin-angiotensin-aldosterone system in patients with chronic
      allograft dysfunction.
AB  - Polymorphism of the gene encoding components of the renin-angiotensin-aldosterone
      synthase system (RAAS) represents an area of intense research of cardiovascular
      disease associations. Numerous studies have addressed the role of RAAS gene
      polymorphisms in the development and progression of renal disease. Also, it has
      been reported that patient with ACE (DD) and angiotensinogen AGT (TT) genotypes
      are associated with chronic allograft dysfunction (CAD). We investigated the
      effects of gene polymorphisms of the renin-angiotensin-aldosterone system in
      renal transplant patients (81 males and 50 females; mean age 29.6+/-10.2 years).
      Genotypes were determined using polymerase chain reaction sequence specific
      primers and PCR followed by RFLP analysis. Renal allograft recipients with
      chronic allograft dysfunction had significantly higher frequencies of the MM
      genotype than those without CAD (P<0.05). The other genetic polymorphisms of the
      RAAS were not associated with CAD. This study proves that determination of AGT
      M235T genotype before transplantation may help identify patients who are at risk
      for chronic renal transplant dysfunction.

PMID- 16635754
TI  - The cellular basis of cardiac allograft rejection. IX. Ratio of naive CD4+CD25+ T
      cells/CD4+CD25- T cells determines rejection or tolerance.
AB  - Naive CD4+ T cells are central to allograft rejection, but include 3-10%
      CD4+CD25+ T cells that induce and maintain immune tolerance. Whether increasing
      the ratio of CD4+CD25+ T cells can inhibit rejection and induce tolerance is not
      known. This study examined the effects that naive CD4+CD25+ and CD4+CD25- T cells
      have on rejection of MHC incompatible PVG cardiac allografts in whole body
      irradiated DA rats. The ratio of CD4+CD25+ T cells to CD4+CD25- T cells was
      increased to examine if this delayed rejection. CD4+CD25- T cells alone restored
      near first set rejection time of 8-10 days and were significantly faster than
      unfractionated CD4+ T cells which nearly always took over 10 days to effect
      rejection. Enriched CD4+CD25+ T cells, either fresh or cultured with IL-2 and
      donor alloantigen, did not restore rejection. Admixing naive CD4+CD25+ T cells
      with CD4+ T cells at a ratio of 1:10 prevented graft destruction by rejection.
      Naive CD4+CD25+ T cells, either fresh or cultured with IL-2 and donor
      alloantigen, at a ratio of 1:1, prevented significant episodes of rejection and
      grafts survived >300 days. These grafts had large areas of normal myocardium but
      had some foci of CD4+, CD8+ and CD25+ cellular infiltration. This study found
      CD4+CD25- T cells were the principal mediators of rejection and naive CD4+CD25+ T
      cells partially inhibited the CD4+CD25- T cells in unfractionated CD4+ T cells.
      Increasing the ratio of naive CD4+CD25+ to CD4+CD25- T cells inhibited rejection
      allowing grafts to survive indefinitely and may induce transplant tolerance,
      without a need for long-term immunosuppression.

PMID- 16635755
TI  - Adolescents and risks: why not change our paradigm?

PMID- 16635757
TI  - Teasing and BMI.

PMID- 16635758
TI  - The impact of community risks and resources on adolescent risky behavior and
      health care expenditures.
AB  - PURPOSE: To examine a nested model that predicts adolescent risky behavior,
      health care use, and health care expenditures from individual characteristics,
      such as age and gender, and community characteristics such as social capital and
      community-level risky behavior rates. METHODS: Claims and encounter data were
      used to classify adolescents enrolled in Florida's Healthy Kids Program into two
      groups: those who engaged in risky behavior (ARB) and those who did not (NRB).
      Hierarchical linear modeling techniques were used to predict the odds of risky
      behavior, the odds of health care use, and health care expenditures based on
      individual and community characteristics. RESULTS: ARB consumed significantly
      more health care services than NRB, and their higher use and charges were
      attributable not only to individual level factors (i.e., age, gender, presence of
      special health care need, metropolitan residence status), but also to community
      level factors (i.e., social capital, risky behavior rates, violence, and
      ethnic/racial composition) as well. In particular, community investment in social
      capital predicted lower levels of risky behavior as well as lower health care
      expenditures. CONCLUSIONS: This information is important in terms of policy
      efforts at providing health care for this vulnerable group of individuals, as
      well as in developing prevention and intervention programs that can be delivered
      through the health care system and via links to community supports.

PMID- 16635759
TI  - Is it worth the RRISK? Evaluation of the RRISK (Reduce Risk Increase Student
      Knowledge) program for adolescents in rural Australia.
AB  - PURPOSE: This study evaluates the effectiveness of an intervention targeting
      adolescent risk-taking associated with drug and alcohol use, driving, and
      celebrating. METHODS: Pre- and post written surveys were administered in 21
      intervention and 19 comparison schools in Northern New South Wales during March
      2003 and 2004. The instrument covered knowledge and attitudes associated with
      self-reported potentially harmful and protective behaviors. Analysis was by multi
      level regression. RESULTS: There were 2705 baseline and 1996 follow-up
      respondents. Adolescents in the intervention area who attended the Reduce Risk
      Increase Student Knowledge (RRISK) seminar demonstrated some significant
      improvements in knowledge, attitudes and behavior compared with those who did not
      attend, and some significant improvements in knowledge compared with students in
      comparison schools. CONCLUSIONS: A well-designed one-day seminar that builds on
      existing curricula, can achieve some significant medium-term benefits in
      knowledge attitudes and behaviors.

PMID- 16635760
TI  - Health status and health-related quality of life in adolescent survivors of
      cancer in childhood.
AB  - PURPOSE: Adolescent survivors of cancer in childhood face particular challenges
      due to their maturational trajectory, including psychosocial adjustments, self
      help skills, intellectual functioning and socialization. To better understand
      these, we assessed the health status and health-related quality of life (HRQL) in
      a 20-year cohort of such survivors in a single institution. METHODS: Health
      status and HRQL were measured with a self-complete questionnaire from the Health
      Utilities Index (HUI) family of multi-attribute, preference-based instruments
      that provide utility scores for single attributes and overall HRQL. RESULTS:
      Eighty-four (42 males, 42 females) of 129 eligible subjects (65%) participated.
      More than 80% of the respondents reported some form of morbidity. Overall HRQL
      utility scores were lower for both the males and females than for corresponding
      members of the Canadian general population. Female survivors self-reported a
      significantly greater burden of morbidity (mean overall HUI2/HUI3 scores: .83/.73
      vs. .90/.84 for males, p < .02), which was most evident in the attributes of
      emotion and cognition. CONCLUSIONS: The majority of adolescent survivors of
      cancer in childhood carry a morbidity burden into their teen and young adult
      years. These findings may guide the support required by this population.

PMID- 16635761
TI  - Use of a children questionnaire of health-related quality of life (KIDSCREEN) as
      a measure of needs for health care services.
AB  - PURPOSE: To check if the expected association is observed between children and
      adolescents' self-perceived health-related quality of life (HRQL) and the use of
      health care services. METHODS: The data come from the pilot test of a European
      measure of HRQL for children and adolescents (KIDSCREEN). Children answered the
      KIDSCREEN 52-item pilot version. Visits to a health professional in the past four
      weeks and hospitalisation in the past 12 months were collected from parents. A
      logistic regression model was adjusted to analyse the relationship between the
      use of health services and HRQL. RESULTS: A total of 2526 children and their
      parents were included in the analysis. Factors associated to visits in the past
      four weeks were poor physical well-being (odds ratio [OR] 1.83; 95% confidence
      interval [CI] 1.42-2.35), and poor school environment (OR 1.32; 95% CI 1.02
      1.71). Low scores on moods and emotions was the associated factor to
      hospitalization in the past 12 months (OR 2.13; 95% CI 1.29-3.81). CONCLUSIONS:
      Children and adolescents are a feasible source for their self-assessment of HRQL.
      They should be taken into account in health care needs studies.

PMID- 16635762
TI  - Acceptability as a key determinant of client satisfaction: lessons from an
      evaluation of adolescent friendly health services in Mongolia.
AB  - PURPOSE: The primary focus of this study is to investigate which characteristics
      of health service quality are most likely to determine client satisfaction with
      health services among adolescents in Mongolia. METHODS: Data were gathered from
      1301 male and female clients. Exit interviews were used to measure client
      satisfaction; 82 clinics were visited. All clients between the ages of 10 and 19
      years were asked to participate in the client exit interview; those who agreed to
      participate completed the questionnaire. Bivariate and multivariate analyses were
      conducted to determine significant associations between service satisfaction and
      the independent variables. All variables showing a significant bivariate
      association with service satisfaction (p < or = .05) were retained for logistic
      regression analyses. RESULTS: The strongest determinant to client satisfaction
      related to acceptability: adequate facility physical environment, receiving
      adequate information about the facility, and if the facility was private (i.e.,
      other people didn't know the services the client received). Additionally, clients
      who said they received some interruptions, either by other health workers or
      clients, were significantly less likely to be satisfied with the services.
      CONCLUSIONS: This study demonstrates the importance of understanding and
      measuring different aspects of health service quality in defining client
      satisfaction. Although both accessibility and acceptability of services have been
      shown to be important in other studies, characteristics relating to acceptability
      emerged as critical in determining client satisfaction among adolescents in
      Mongolia. Efforts to improve health service delivery to adolescents need to
      understand and address the "adolescent friendly" characteristics that are most
      salient, and least fulfilled, in each particular context.

PMID- 16635763
TI  - Does parental unemployment affect adolescents' health?
AB  - PURPOSE: To explore the associations between mother's and father's employment
      status separately and together and the subjective health of children; and how
      parental education and financial strain can modify these associations. METHODS:
      Data were obtained from 2836 respondents aged 14 to 22 years (mean age 17.7
      years). Logistic regression models were used with three subjective health
      indicators: self-rated health, long-standing illness, and health complaints; and
      ANOVA with one indicator: long-term well-being. Father's and mother's employment
      status was coded as follows: employed, short-term unemployed (less than one
      year), long-term unemployed (more than one year), and parental employment status
      as follows: both employed, one unemployed and both unemployed. All analyses were
      done separately for males and females. RESULTS: Father's long-term unemployment
      was a significant predictor of moderate self-rated health and low long-term well
      being among males and females. Mother's long-term unemployment was negatively
      associated with self-rated health of females and long-standing illness among
      males. No associations between father's or mother's unemployment and occurrence
      of health complaints or between short-term unemployment and worse health of
      children were found. Unemployment of both parents negatively influenced self
      rated health of both genders and long-term well-being of females. After including
      parental education and financial strain in the model, the negative effect of
      father's and mother's long-term unemployment on health remained significant.
      However, influence of unemployment of both parents on health disappeared after
      adjusting for these variables. CONCLUSIONS: Parental long-term unemployment
      (especially of fathers) is negatively associated with adolescents' subjective
      health, and this association remains even when the social class and financial
      strain is taken into account.

PMID- 16635764
TI  - Victimization and health among indigent young women in the transition to
      adulthood: a portrait of need.
AB  - PURPOSE: To understand victimization by physical and sexual violence and its
      association with physical and behavioral health in a probability sample of
      sheltered homeless and low-income-housed young women in the transition to
      adulthood (ages 18 through 25). METHODS: Participants were 224 women ages 18
      through 25 who were selected by means of a stratified random sample from 51
      temporary shelter facilities (N = 94) and 66 Section 8 private project-based
      Housing and Urban Development (HUD)-subsidized apartment buildings (N = 130) in
      Los Angeles County, California. Women completed structured interviews. RESULTS:
      Forty-one percent of the sample had been physically or sexually victimized as
      children and 51% had been victimized since turning 18. Young women who
      experienced victimization were significantly (p < .05) more likely than non
      victimized women to have a sexually-transmitted disease (STD) other than HIV/AIDS
      or Hepatitis B or C, vaginal discharge or bleeding and pelvic pain in the past 6
      months, and past-12 month screening diagnoses of drug abuse/dependence and
      depression. Victimized women were also significantly more likely to use alcohol
      to intoxication and drugs, including crack and amphetamines, during the past 6
      months, and to have experienced psychological distress and poor self-esteem.
      CONCLUSIONS: This study highlights striking rates of victimization and its
      association with physical and behavioral health problems among indigent young
      women during the period of emerging adulthood. This portrait of need communicates
      an urgency to develop multifaceted programs for such women to help them
      successfully navigate the transition to adulthood and realize their full
      potential as adults.

PMID- 16635765
TI  - Child sexual abuse in Henan province, China: associations with sadness,
      suicidality, and risk behaviors among adolescent girls.
AB  - PURPOSE: To assess the prevalence of child sexual abuse (CSA) and possible
      effects on mental health and risky behavior among female adolescents living in
      China. METHOD: A retrospective survey was conducted among 351 female students in
      a medical secondary school in the central China province of Henan in June 2004.
      The anonymous, self-administered questionnaire included items about unwanted
      sexual experiences before age 16, depression, suicidality, and risky health
      related behaviors. RESULTS: Over one in five young women (21.9%) reported at
      least one type of CSA (any one of 12 forms of nonphysical contact and physical
      contact CSA) before the age of 16 years, with one in every seven (14.0%)
      reporting CSA involving physical contact. Risk of CSA was not associated with
      parents' education level, existence of siblings, or rural/urban residence during
      childhood. Although some indicators of poor mental health were slightly elevated
      among girls who had experienced noncontact CSA only, the most significant impact
      is among victims of contact CSA, including higher rates of depression,
      overwhelming sadness, suicidal thinking and planning, alcohol drinking, smoking,
      fighting, and having sexual intercourse. CONCLUSIONS: The risk of CSA in this
      sample of Chinese female adolescents seems similar to young women in many Western
      countries, and the pattern of associated mental health and behavioral problems is
      entirely consistent with international research.

PMID- 16635766
TI  - The effects of religious affiliation on sexual initiation and condom use in
      Zambia.
AB  - PURPOSE: To determine whether religious affiliation reduces HIV risk among young
      women in Zambia, and to examine the effects of religious affiliation on sexual
      initiation and on condom use during first sexual experience. METHODS: Data from a
      representative probability sample of 5534 women aged 13-20 years was analyzed.
      The instrument included questions on sexual initiation, condom use during first
      sex, religious affiliation, and sociodemographic characteristics of respondents.
      Statistical tests were performed at the bivariate and multivariate levels. Cox
      proportional hazards and logistic regression were used at the multivariate
      levels. Standard errors were adjusted for the "clustering" effect found in data
      from multistage cluster samples. RESULTS: Affiliation with religious groups that
      excommunicate members for engaging in premarital sex, and that oppose condom use
      has both positive and negative effects on behaviors that carry the risk of HIV
      infection; young women affiliated with conservative groups are more likely to
      delay sexual initiation but less likely to use condoms during first sex.
      CONCLUSIONS: Denominations that are not only strongly opposed to premarital sex
      and condom use, but are able to exercise control over adolescents through
      socialization or the threat of social exclusion, are likely to create conflicting
      behaviors among adolescents that cancel each other in terms of HIV risk. Overall,
      these findings suggest that affiliation with conservative religious groups is
      unlikely to reduce the risk of HIV infection. Additional studies are recommended.

PMID- 16635767
TI  - The protective value of social capital against teen pregnancy: a state-level
      analysis.
AB  - PURPOSE: To investigate whether social capital may explain differences in teen
      pregnancy rates in the contiguous United States. METHOD: State-level
      correlational analyses were conducted. Predictor variables included social
      capital, income inequality, and poverty. MAIN OUTCOME MEASURE: State-level rates
      of pregnancy for girls 15-19 years old. RESULTS: In bivariate analyses, social
      capital was inversely correlated with teen pregnancy rates. The obtained
      correlation was strong (r = -.78) and achieved significance (p < .001). Poverty
      and income inequality were also significantly correlated with teen pregnancy
      rates, but the magnitude of these correlations was lower. In a linear regression
      model, poverty failed to retain significance; however, income inequality achieved
      significance and produced a Beta value of .24 (p = .017). Social capital was
      nonetheless a much stronger multivariate predictor of teen pregnancy rates
      (producing a Beta value of -.672). CONCLUSION: Findings from this state-level
      analysis suggest that social capital may explain differences between states with
      respect to teen pregnancy rates. Thus, social capital may play an important role
      in the prevention of teen pregnancy. This initial finding warrants subsequent
      empirical investigations designed to identify strategies that can be employed to
      foster the creation of social capital in communities and entire states.

PMID- 16635768
TI  - Attitude toward physical activity in normal-weight, overweight and obese
      adolescents.
AB  - PURPOSE: To investigate differences in physical activity and attitude toward
      physical activity in adolescents with different degrees of overweight and explore
      whether the prediction of physical activity by attitude is moderated by level of
      overweight. METHODS: Subjects were divided into a normal-weight group (n = 37,
      18.8 +/- 1.2 kg/m2), an overweight group (n = 28, 25.9 +/- 1.3 kg/m2), and an
      obese group (n = 24, 33.7 +/- 4.1 kg/m2). Mean age was 14.6 +/- 1.2 years, with
      72% girls. Physical activity was estimated using the Baecke Questionnaire.
      Attitude was measured by assessing perceived benefits and barriers. RESULTS:
      Participation in sports was higher in normal-weight compared with overweight (p <
      .05) and obese (p < .01) subjects. There was no difference in leisure-time
      physical activity between groups. Perceived benefits did not differ between
      groups, but normal-weight subjects perceived less barriers ('physical
      complaints', 'not being good at it', 'insecure about appearance', 'not liking
      it') than their overweight (p < .05) and obese (p < .001) counterparts. Obese
      adolescents had a less positive attitude compared with their normal-weight (p <
      .001) and overweight (p < .05) peers. Sport participation was significantly
      predicted by the perceived benefit 'pleasure' (p < .05) and by the perceived
      barrier 'not liking it' (p < .001), after taking into account level of
      overweight. The association between sport participation and attitude was not
      moderated by level of overweight. CONCLUSIONS: This study demonstrates that
      overweight and obese adolescents show lower sport participation and have a less
      positive attitude toward physical activity. Interventions in youngsters with
      weight problems should try to increase participation in sports by making
      activities more fun and attractive for these youngsters.

PMID- 16635769
TI  - Psychosocial and behavioral correlates of dieting among overweight and non
      overweight adolescents.
AB  - PURPOSE: To examine correlates of dieting behavior in overweight and non
      overweight youth. METHODS: Data came from Project EAT (Eating Among Teens), a
      study of eating and weight-related attitudes, behaviors, and psychosocial
      variables among 4746 adolescents in public schools. Logistic regression was used
      to compare dieters and non-dieters, and to examine interactions of dieting and
      overweight status. RESULTS: Approximately one third (31.8%) of the sample was
      overweight. Dieting in the previous year was reported by 55.2% of girls and 25.9%
      of boys. Dieting was associated with similarly elevated rates of extreme weight
      control behaviors, body dissatisfaction, and depression in both the non
      overweight and overweight groups for both boys and girls. Girls reporting dieting
      behavior in both the non-overweight and overweight groups had similarly elevated
      risk for cigarette use, alcohol use, and marijuana use. CONCLUSIONS: The negative
      correlates of dieting are similarly common among teens of varying weight status.
      These data suggest that dieting may not be a preferred method of weight
      management, even for overweight adolescents. Regardless of weight status, dieting
      may be a marker for other unhealthy behaviors and depressed mood in adolescents.

PMID- 16635770
TI  - Understanding the food choice process of adolescents in the context of family and
      friends.
AB  - PURPOSE: To understand from the adolescents' own perspective the decision-making
      processes they use to make food choices on an everyday basis and how they resolve
      their need for personal control over food choices with the values of family and
      peers. METHODS: A sample of 108 adolescents, aged 11-18 years, were individually
      interviewed. They were asked in a simulated task to choose a lunch from a menu of
      offerings and give reasons for their choices. In addition, open-ended questions
      probed for meal structures, dinners, perceptions of degree of choice, role of
      family and peers. Interviews were audio-taped, transcribed, coded, and analyzed
      for emerging themes. RESULTS: Primary food choice criteria were taste,
      familiarity/habit, health, dieting, and fillingness. Lunches had a definite
      structure, and lunches differed from dinners. The food choice process involved
      personal food decision-making rules such as trade-offs among choice criteria
      within a meal (e.g., taste for core items and health for secondary items), and
      between lunches with peers (taste) and family dinners (health); negotiation
      patterns with the family (autonomy versus family needs); and interactions with
      peers. CONCLUSIONS: The food choice process for most adolescents seemed to
      involve cognitive self-regulation where conflicting values for food choices were
      integrated and brought into alignment with desired consequences. Educators and
      practitioners should recognize the dilemmas adolescents face in making food
      choices and help them develop strategies for balancing less healthful with more
      healthful food items, through: (a) personal food decision-making rules, (b)
      effective negotiations with family members; and (c) appropriate interaction
      patterns with peers.

PMID- 16635771
TI  - Oral health behavior and self-esteem in Swedish adolescents over four years.
AB  - PURPOSE: Our analysis of data collected in 1995 showed that 12-year-olds' self
      esteem was associated with demographic/socioeconomic background variables and
      lifestyle variables and with the quality of the variable "oral health behavior."
      The study reported here was conducted to identify changes at ages 14 (in 1997)
      and 16 years (in 1999) in the strength of the association between self-esteem and
      "oral health behavior." METHODS: In 1995, 3370 12-year-olds answered questions
      about their demographic/socioeconomic background, personal attitudes/resources,
      and lifestyle, including "oral health behavior." Two and four years later the
      same study group (3105 14-year-olds in 1997 and 2836 16-year-olds in 1999)
      answered similar questionnaires with redefinition of "oral health behavior" as
      "tooth-brushing." Multivariate and logistic regression analyses were conducted
      using "self-esteem" and "oral health behavior/tooth-brushing" as the dependent
      variables. The association was also analyzed between "oral health behavior/tooth
      brushing" and components of "self-esteem" (two cognitive: "How do you think your
      teacher would rate your school work?," "How do you think you are performing in
      school?," and one emotional: "How content are you with your body/looks?").
      RESULTS: The association between "self-esteem" and "oral health behavior/tooth
      brushing" disappeared during adolescence, but whereas the influence of cognitive
      components decreased, the influence of the emotional component increased.
      Overall, the strongest predictor of poor oral health behavior (tooth-brushing
      less than twice per day) was male gender. CONCLUSION: The motives for good oral
      health behavior changed from age 12 to age 14 years.

PMID- 16635772
TI  - Prevalence and interrelations of cardiovascular risk factors in urban and rural
      Mexican adolescents.
AB  - PURPOSE: To examine the prevalence of coronary risk factors in Mexican
      adolescents, and their relations to school type, gender, and residence in urban
      and rural areas. METHODS: A cross-sectional survey was conducted in 3121 junior
      high school students, aged 12 to 16 years, attending urban schools (eight public,
      n = 1850, two private, n = 480) and three rural public (n = 791) schools. Weight,
      height, waist circumference, blood pressure, and fasting glucose and lipid
      lipoprotein levels were measured. Tobacco smoking and physical activity were also
      ascertained. The prevalence rates of cardiovascular risk factors were determined
      by gender and school type. RESULTS: Obesity, overweight, high blood pressure,
      cigarette smoking, and physical inactivity were higher for urban than rural
      adolescents. The prevalence of the low HDL-C level was exceedingly high in
      adolescents of three school types (> 30%) but particularly in male rural students
      (48.9%). Compared with rural students, high LDL-cholesterol was twice as high in
      private schoolchildren. The prevalence of impaired fasting glucose was .35% in
      the whole population and much higher in obese males (1.6%) and obese females
      (2.4%). CONCLUSIONS: Our findings highlight an epidemic of coronary risk factors
      mainly in adolescents living in the urban area, suggesting the importance of
      environmental factors.

PMID- 16635773
TI  - The prevalence of folic acid deficiency among adolescent girls living in Edirne,
      Turkey.
AB  - PURPOSE: A high incidence of iron-deficiency is a common observation among
      adolescent girls, whereas only limited data are available regarding the folic
      acid status of this group. This study was designed to determine the prevalence of
      biochemical folic acid deficiency in a group of Turkish adolescent girls.
      METHODS: We surveyed the serum folic acid, complete blood count, and dietary
      folic acid intake of Turkish adolescent girls after using three-day self-reported
      food intakes in urban and rural areas of Edirne, Turkey. RESULTS: A sample
      population was composed of 704 adolescent girls; their serum folic acid levels
      were found to be adequate for 37.6% (> or = 6 ng/mL), marginal for 46% (3 to 5.9
      ng/mL), and at deficient levels for 16.3% (< 3 ng/mL). Folic acid deficiencies
      were found in 20.1% (36 of 179) and 14.7 % (61 of 416) of adolescent girls from
      rural and urban areas, respectively. Self-reported three-day folic acid intakes
      were correlated with the corresponding blood values for this nutrient. In the
      logistic regression analysis, three factors emerged as significant independent
      predictors of folic acid deficiency: low income (odds ratio [OR]: 2.4, 95%
      confidence interval [CI]: 1.3-4.2, p < .001), low vitamin C (OR: 1.9, 95% CI: 1.1
      3.5, p < .05), and folic acid intake (OR: 4.8, 95% CI: 2.8-8.1, p < .001).
      CONCLUSION: Data from the present study may indicate that serum folic acid is low
      in a group of Turkish adolescent girls. These low values appear to be associated
      with low income, and low dietary intakes of folic acid and vitamin C.

PMID- 16635774
TI  - Adolescent quality of life and satisfaction with care.
AB  - PURPOSE: 1) To describe adolescents' responses to a client satisfaction and
      family-centered care survey; 2) to examine the relationship between satisfaction
      with health care and health-related quality of life (HRQL) among these
      adolescents; and 3) to determine if adolescents and their parents differ in their
      satisfaction with services. METHODS: We recruited 104 adolescents who attended
      the Alberta Children's Hospital pediatric neurology clinic. Each family completed
      the Client Satisfaction Questionnaire (CSQ), the Family Centered Care Survey
      (FCCS), the Measure of Processes of Care (MPOC) survey, the Give Youth a Voice
      (GYV) survey, and the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Of
      116 eligible families, 104 (90%) completed the study. The majority (83%) of
      adolescents were satisfied with services provided. Adolescents who were very
      satisfied on the CSQ and the FCCS had higher PedsQL psychosocial scores (p = .009
      and .013, respectively). Multivariate analysis revealed that adolescents'
      psychosocial HRQL was the most significant predictor of their satisfaction with
      care (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01 to 1.06). There was
      a difference between parents' and adolescents' responses to the FCCS (p = .02),
      with adolescents being less satisfied overall. CONCLUSIONS: Given that
      adolescents and parents differ in their satisfaction with health care, it is
      helpful to have direct input from adolescents on health services surveys. The
      positive relationship between adolescents' psychosocial HRQL and satisfaction
      with care highlights the potential impact of emotional health on subjective
      rating of services. Further studies should determine if improvement in
      adolescents' mental health is associated with greater satisfaction with health
      care and/or increased adherence with medical treatments.

PMID- 16635775
TI  - Socioeconomic status and medication prescription patterns in pediatric asthma in
      Canada.
AB  - PURPOSE: To investigate whether the socioeconomic status of children and
      adolescents with asthma is associated with optimal use of asthma medications in a
      health care system that provides free access to prescribed medications. METHODS:
      A cohort of 29,018 children (5-12 y) and adolescents (13-17 y) with asthma was
      reconstructed from the administrative health database of the Regie de l'assurance
      maladie du Quebec in Canada. Adherence to the Canadian Asthma Guidelines was
      compared between low-income patients (patients living in families receiving
      social assistance) and higher-income patients (patients living in middle-class
      families with working parents). Both groups of patients had free, universal
      access to medical care and prescribed medications. Patients were considered
      adherent if they had: (1) 10 doses or fewer of a short-acting beta2-agonist
      (SABA) per week or (2) greater than 10 doses of a SABA per week plus greater than
      1,000 microg of beclomethasone chlorofluorocarbon (CFC) per day. A second
      definition of adherence was used in which the 10 doses of SABA were replaced by 3
      doses. RESULTS: Our cohort comprised 7,454 adolescents and 21,564 children.
      Within each definition, low-income adolescents had similar rates of adherence as
      higher-income adolescents (p = .08-.4). Low-income children, however, had lower
      rates of adherence than higher-income children when the first definition of
      adherence was used (76% vs. 80%; p < .001). CONCLUSION: Our study showed that
      socioeconomic status had a small influence on the likelihood of receiving
      treatment in adherence with the Canadian Asthma Guidelines among children,
      whereas no association was detected among adolescents.

PMID- 16635776
TI  - Do physicians discuss needed diet and nutrition health topics with adolescents?
AB  - PURPOSE: Preventive services guidelines recommend screening all adolescents for
      diet habits, physical activity and growth, counseling underweight teens about
      body image and dieting patterns, and counseling overweight or obese teens about
      dietary habits and exercise. In this study, we assess whether adolescents at risk
      for overweight or for eating disorders have discussed recommended diet and
      nutrition topics with their physicians. METHODS: We surveyed 14-18-year-old
      adolescents who had been seen for well care in primary care pediatric and family
      medicine practices. Adolescents self-reported their weight, height, body image,
      dieting habits, and issues they had discussed with their clinicians. Body mass
      index (BMI) was used to define those "at risk for an eating disorder" (< 5% BMI),
      "at risk of becoming overweight" (85%-95% BMI), and "overweight" (> 95% BMI).
      RESULTS: A total of 8384 adolescents completed surveys (72% completion rate).
      Nearly one-third of adolescents were "at risk" or overweight. Females were less
      likely to be overweight than males (9.4% vs. 15.7%; p < .001). Although 26.4%
      were attempting to lose weight, only 12.2% of all teens were actually overweight.
      Exercise and restricting intake were the preferred methods of weight loss.
      Physicians routinely discussed adolescents' weight during visits, and were more
      likely to discuss it with those "at risk" (p < .001). Body image was more often
      discussed with girls than with boys (52% vs. 44.6%, p < .001) and with those at
      risk (51.6% vs. 45.5%; p < .001). Discussion of healthy eating and weight loss
      occurred more often with adolescents "at risk" for becoming overweight (p <
      .001). CONCLUSIONS: Many adolescents are at risk for being overweight or are
      currently overweight, confirming the importance of clinicians discussing diet and
      nutrition health topics with all teens. Many adolescents also misclassify their
      body image, and hence perceive their body image to be different from their actual
      BMI; clinicians should discuss body image with all adolescents, not just those at
      risk for eating disorders. Better interventions are needed to promote healthy
      nutrition and physical activity to all adolescents.

PMID- 16635777
TI  - The co-occurrence of substance use and high-risk behaviors.
AB  - Study findings suggest that alcohol and methamphetamine use heighten the risk for
      violence, multiple sexual partners, and unprotected sexual intercourse. Although
      the odds of engaging in risky behaviors increased dramatically with alcohol and
      methamphetamine use, the majority of subjects did not become involved in high
      risk behaviors even though they used alcohol and illicit drugs.

PMID- 16635778
TI  - Underage driving as an indicator of risky behavior in children and adolescents.
AB  - Driving among children and adolescents below the legal driving age in Texas was
      examined. There were 4170 accidents between 1995 and 2000 (66.5% involved
      injury/fatality). Drivers were more often male, and underage driving was greatest
      during the late afternoon/early evening. Risk of severe injury or death was
      inversely related to speed and nighttime driving, and was greater in rural areas,
      in accidents involving passengers and among black children and youth compared
      with white.

PMID- 16635779
TI  - Risk factors for violence and violence-related injuries among 14- to 18-year-old
      Finns.
AB  - A random sample of 14- to 18-year-old Finns (3319 boys, 3890 girls) were sent a
      questionnaire on the occurrence of violence and violence-related injury.
      Altogether, 76% responded. Weekly stress symptoms, depressive mood, smoking,
      drunkenness, peer drug use, previous unintentional injury, and not living with
      both parents predicted both incidents.

PMID- 16635780
TI  - The impact of gender-role nonconforming behavior, bullying, and social support on
      suicidality among gay male youth.
AB  - This study hypothesized that gender-role nonconformity is associated with
      suicidality, and bullying mediates this relationship. Gay males retrospectively
      answered questions pertaining to elementary, middle, and high school. Support for
      the hypotheses was found. Results can help screen gay youth for suicidality and
      support the need for policies prohibiting harassment based on sexual orientation.

PMID- 16635781
TI  - Service utilization and the life cycle of youth homelessness.
AB  - The study sought to describe service utilization patterns of homeless youth based
      on their life cycle stage. Ninety-nine percent of participants accessed services.
      Medical service utilization was highest among youth who were attempting to leave
      the street. Drug-related service utilization was lowest among youth most
      entrenched in street life.

PMID- 16635782
TI  - Disordered eating attitudes among elementary school population.
AB  - Disturbed eating attitudes and behaviors among elementary school children were
      evaluated using the Children's Eating Attitude Test. Our findings demonstrate
      that students in early adolescence have disturbed eating attitudes and behaviors.
      We recommend screening for eating disorders in this group in order to provide
      primary and secondary prevention.

PMID- 16635783
TI  - Eating and weight control behaviors among middle school girls in relationship to
      body weight and ethnicity.
AB  - This study examined the links among body mass index (BMI), weight control
      practices, binge eating, and eating disorders in 1164 middle school girls. Both
      the prevalence and frequency of weight control behaviors increased as BMI
      increased, but binge eating was reported approximately equally by girls across
      the BMI spectrum.

PMID- 16635784
TI  - National Institutes of Health Consensus Development Project on Criteria for
      Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical
      Trials Working Group report.
AB  - The complexity of chronic graft-versus-host disease (GVHD) and the lack of
      established research methods have made it difficult to design, conduct, and
      analyze clinical trials involving subjects with this disease, even when promising
      treatment options are available. This consensus document was developed to offer
      an approach for overcoming these obstacles. Clinical trials in chronic GVHD
      should adhere to principles of good trial design and practice. Inclusion and
      exclusion criteria should allow as many subjects to participate as possible
      without compromising the interpretation of results. Pre-enrollment assessment of
      chronic GVHD characteristics should be standardized. The protocol should provide
      clear guidance about administration of study medication and other interventions.
      Methods of assessing response should be defined and validated in advance.
      Efficacy endpoints should be selected to reflect clinical benefit. Expert
      biostatistical support is needed to ensure the validity and reliability of trial
      results. The use of consistent standards in clinical trial designs to evaluate
      agents that have activity in pathogenic pathways could facilitate advances in the
      treatment of chronic GVHD.

PMID- 16635785
TI  - Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host
      disease after allogeneic hematopoietic stem cell transplantation.
AB  - Iron overload presenting as exacerbation of hepatic graft-versus-host disease
      (GVHD) after allogeneic hematopoietic stem cell transplantation has not been
      previously described. We report 6 patients with established hepatic GVHD in whom
      iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation,
      77%) resulting from a lifetime median of 20 units of packed red blood cell
      transfusions was manifested by worsening of liver function. Liver biopsies
      performed in 4 patients confirmed severe iron overload and also hepatic GVHD.
      Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for
      the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy
      resulted in normalization of liver function at a median of 7 months and of serum
      ferritin at a median of 11 months. Immunosuppressive therapy was successfully
      tapered in all 4 patients who completed the phlebotomy program, and this
      supported the impression that iron overload, rather than GVHD, was the principal
      cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76
      months) from the transplantation and 25 months (range, 5-36 months) from ferritin
      normalization, all 4 patients require maintenance phlebotomy. We conclude that
      iron overload can mimic GVHD exacerbation, thus resulting in unnecessary
      continuation or intensification of immunosuppressive therapy for GVHD, and that
      maintenance phlebotomy is necessary after successful iron-reduction therapy.

PMID- 16635786
TI  - Evidence of donor-derived hematologic malignancies after hematopoietic stem cell
      transplantation.
AB  - Increasing the upper age limit for recipients of hematopoietic stem cell
      transplantation (HCT) naturally has also increased the age of the corresponding
      related donor population. Because aging is a risk factor for malignancies, the
      risk of transferring preexisting malignant or premalignant hemopoietic clones in
      the process of HCT might be expected to increase as well. Anecdotal clinical
      cases of malignancies derived from donor cells in patients undergoing HCT have
      been published since 1971. In this article, we report 12 new cases that fit 2
      different categories: (1) cases in which clones with characteristics of
      lymphohemopoietic malignancies were transferred from the donors to the recipients
      and (2) cases in which the malignant clone evolved from healthy donor cells once
      transplanted into the recipient. Donors in the first group were significantly
      older than donors in the second group. A more systematic examination of the
      prevalence and biology of donor malignancies would merit study.

PMID- 16635787
TI  - Immune tolerance to self-major histocompatibility complex class II antigens after
      bone marrow transplantation: role of regulatory T cells.
AB  - The immune system undergoes rapid reconstitution after autologous or syngeneic
      bone marrow transplantation with the re-establishment of tolerance to self
      antigens. Administration of drugs such as cyclosporine that inhibit thymic
      dependent clonal deletion disrupts the reconstitution of the immune system. In
      the absence of a peripheral regulatory T cells eliminated by the preparative
      regimen, systemic autoimmunity with pathology similar to graft-versus-host
      disease often develops. Moreover, the resolution of autoaggression is dependent
      on the reconstitution of CD4+ regulatory T cells. This study examined the
      specificity and function of this regulatory population assessed ex vivo that
      plays a critical role in down-regulating the autoreactive T lymphocyte response
      in cyclosporine-induced syngeneic graft-versus-host disease. The results suggest
      that both the antigen-specific regulatory and pathogenic effector T cells
      recognize a common peptide antigen framework (CLIP, a peptide derived from the
      invariant chain) presented by major histocompatibility complex class II
      molecules. Analysis of the CD4+ T-cell compartment revealed two subsets of CLIP
      reactive T cells that differentially require the N- and C-terminal flanking
      domain of this peptide. Regulatory function is associated with the cells that
      require the C-terminal flanking domain. This population expresses the Foxp3
      nuclear transcription factor and plays a critical role in re-establishing
      tolerance to self-major histocompatibility complex class II antigens. In addition
      to suppressing the production of type 1 cytokines, these regulatory T cells can
      direct the apoptotic death of the pathogenic autoreactive lymphocytes. This study
      also suggests that the development of functional regulatory activity is an active
      response initiated by the presence of autoreactive lymphocytes that can present
      the target antigen (major histocompatibility complex class II CLIP) to the
      regulatory T cells. Moreover, this process can be mimicked by peptide antigen in
      the absence of the pathogenic effector lymphocytes leading to the development of
      functional regulatory T-cell activity.

PMID- 16635788
TI  - Vascular endothelial cells produce soluble factors that mediate the recovery of
      human hematopoietic stem cells after radiation injury.
AB  - The risk of terrorism with nuclear or radiologic weapons is considered to be high
      over the coming decade. Ionizing radiation can cause a spectrum of hematologic
      toxicities, from mild myelosuppression to myeloablation and death. However, the
      potential regenerative capacity of human hematopoietic stem cells (HSCs) after
      radiation injury has not been well characterized. In this study, we sought to
      characterize the effects of ionizing radiation on human HSCs and to determine
      whether signals from vascular endothelial cells could promote the repair of
      irradiated HSCs. Exposure of human bone marrow CD34+ cells to 400 cGy caused a
      precipitous decline in hematopoietic progenitor cell content and primitive cells
      capable of repopulating nonobese diabetic/severe combined immunodeficient mice
      (SCID-repopulating cells), which was not retrievable via treatment with
      cytokines. Conversely, culture of 400 cGy-irradiated bone marrow CD34+ cells with
      endothelial cells under noncontact conditions supported the differential recovery
      of both viable progenitor cells and primitive SCID-repopulating cells. These data
      illustrate that vascular endothelial cells produce soluble factors that promote
      the repair and functional recovery of HSCs after radiation injury and suggest
      that novel factors with radiotherapeutic potential can be identified within this
      milieu.

PMID- 16635789
TI  - Effect of body mass index on mortality of patients with lymphoma undergoing
      autologous hematopoietic cell transplantation.
AB  - High-dose therapy with autologous hematopoietic cell transplantation (auto-HCT)
      is frequently used to improve outcomes in lymphoma. However, small studies
      suggest a survival disadvantage among obese patients. Using a retrospective
      cohort analysis, we studied the outcomes of 4681 patients undergoing auto-HCT for
      Hodgkin or non-Hodgkin lymphoma between 1990 and 2000 according to body mass
      index (BMI). Four groups categorized by BMI were compared by using Cox
      proportional hazards regression to adjust for other prognostic factors. A total
      of 1909 patients were categorized as normal weight (BMI 18-25 kg/m2), 121 as
      underweight (BMI<18 kg/m2), 1725 as overweight (BMI>25-30 kg/m2), and 926 as
      obese (BMI>30 kg/m2) at the time of HCT. Outcomes evaluated included overall
      survival, relapse, transplantation-related mortality (TRM), and lymphoma-free
      survival. TRM was similar among the normal, overweight, and obese groups; the
      underweight group had a higher risk of TRM (relative risk [RR], 2.46; 95%
      confidence interval [CI], 1.59-3.82; P<0.0001) compared with the normal-BMI
      group. No differences in relapse were noted. Overall mortality was higher in the
      underweight group (RR, 1.48; 95% CI, 1.17-1.88; P=.001) and lower in the
      overweight (RR, 0.87; 95% CI, 0.79-0.96; P=.004) and obese (RR, 0.76; 95% CI,
      0.67-0.86; P<.0001) groups compared with the normal-BMI group. In light of our
      inability to find differences in survival among overweight, obese, and normal
      weight patients, obesity alone should not be viewed as a contraindication to
      proceeding with auto-HCT for lymphoma when it is otherwise indicated.

PMID- 16635790
TI  - Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem
      cell transplantation.
AB  - Sirolimus is increasingly used in transplantation for prevention and treatment of
      graft-versus-host disease and organ rejection. Voriconazole is contraindicated
      when used concomitantly with sirolimus because of a substantial increase in
      sirolimus drug exposure with unadjusted dosing, but voriconazole is also
      considered the best initial treatment of invasive aspergillosis and other fungal
      infections. Patients who received voriconazole and sirolimus concomitantly were
      identified by a review of the medical records of all allogeneic hematopoietic
      stem cell recipients at our institution from September 1, 2002, to June 1, 2005.
      Data including baseline characteristics, indications for both drugs, and
      potential adverse effects were evaluated. Eleven patients received voriconazole
      and sirolimus concomitantly for a median of 33 days (range, 3-100 days). In 8
      patients whose sirolimus dose was initially reduced by 90%, trough sirolimus
      levels were similar to those obtained before the administration of voriconazole;
      no obvious significant toxicity from either drug was observed during
      coadministration. Serious adverse events were observed in 2 patients in whom
      sirolimus dosing was not adjusted during voriconazole administration. Sirolimus
      and voriconazole may be safely coadministered if there is an empiric initial 90%
      sirolimus dose reduction combined with systematic monitoring of trough levels.

PMID- 16635791
TI  - Thymoglobulin prevents chronic graft-versus-host disease, chronic lung
      dysfunction, and late transplant-related mortality: long-term follow-up of a
      randomized trial in patients undergoing unrelated donor transplantation.
AB  - This is an update of a randomized study on antithymocyte globulin (ATG;
      Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow
      transplantation from unrelated donors. The median follow-up for surviving
      patients is 5.7 years. At last follow-up, chronic graft-versus-host disease
      (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P=.05), and
      extensive chronic GVHD was present in 41% and 15%, respectively (P=.01). Chronic
      lung dysfunction was diagnosed in 51% versus 19% of patients (P=.005). Forced
      vital capacity decreased significantly with time in non-ATG patients (P=.005),
      but not in patients who received ATG (P=.30). The proportion of patients with
      Karnofsky scores of >or=90% at 4 years was 57% versus 89% in non-ATG versus ATG
      patients (P=.03). The actuarial 6-year survival for all patients randomized was
      31% versus 44% (non-ATG versus ATG; P=.80). The cumulative incidence of
      transplant-related mortality was 51% versus 41% (P=.70) and of relapse was 32%
      versus 40% (P=.90). For patients who survived 1 year, transplant-related
      mortality was 25% versus 3% (P=.03), and actuarial survival was 58% versus 85%
      (P=.09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides
      significant protection against extensive chronic GVHD and chronic lung
      dysfunction, reduces late transplant mortality, and improves quality of life in
      patients undergoing unrelated donor transplantation.

PMID- 16635792
TI  - Altered functional status of the hypothalamic dopaminergic tone in patients with
      chronic graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation: a pilot study.
AB  - We compared the functional status of the hypothalamic dopaminergic tone in
      patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      with chronic graft-versus-host disease (GVHD) with that observed in patients with
      allo-HSCT without chronic GVHD and in healthy controls. The effect of acute
      dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL)
      concentrations was evaluated. Twenty volunteers, 20 to 52 years of age,
      seronegative for both hepatitis C virus and the human immunodeficiency virus,
      were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with
      leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT,
      5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and
      2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations
      were measured both fasting and after intravenous administration of metoclopramide
      (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2
      were older than those in groups 1 and 3 (P<.018), but their body mass index was
      similar. Fasting serum PRL concentrations were similar among the 3 groups;
      however, group 2 had higher PRL concentrations throughout the test (P<.001) and a
      greater area under the PRL curve than groups 1 and 3 (P<.001), without
      differences between the last 2 groups. The differences remained significant after
      adjustment for age (P<.01). Our results in a small group of patients with chronic
      GVHD after allo-HSCT suggest the existence of an increased functional level of
      their hypothalamic dopamine tone, which would favor a tendency toward a
      diminished endogenous production, release of pituitary PRL, or both. This could
      represent an adaptive mechanism aiming to maintain circulating PRL concentrations
      within a physiological range.

PMID- 16635793
TI  - Reduced incidence of acute and chronic graft-versus-host disease with the
      addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen.
AB  - To reduce the incidence of graft-versus-host disease (GVHD), we added
      Thymoglobulin (THY) to dose-adjusted oral busulfan plus cyclophosphamide
      (targeted BUCY). The starting dose of THY was 4.5 mg/kg given over days -3, -2,
      and -1, escalated in steps of 1.5 mg/kg in cohorts of 15 evaluable patients.
      Escalation was dependent on acute GVHD incidence and Epstein-Barr virus
      reactivation. Fifty-six patients with myelodysplastic syndrome and other myeloid
      disorders underwent transplantation with peripheral blood progenitor cells from
      related (n=30) or unrelated (n=26) donors. All but 2 patients achieved
      engraftment, and 56% survived in remission beyond 1 year. The incidence of acute
      GVHD was 50%, and that of chronic GVHD was 34%. The highest THY dose was 6.0
      mg/kg, a dose at which 1 patient experienced Epstein-Barr virus reactivation.
      Nine patients did not receive the prescribed THY dose. Results were comparable
      for related and unrelated transplants and for patients given 4.5 or 6.0 mg/kg
      THY. Among 27 myelodysplastic syndrome patients (14 with related and 13 with
      unrelated donors) who underwent transplantation concurrently with targeted BUCY
      without THY, the incidence of acute and chronic GVHD was 82%. Thus, THY 4.5 to
      6.0 mg/kg seemed beneficial for GVHD prevention in BUCY-conditioned patients who
      underwent transplantation with peripheral blood progenitor cells, although
      relapse-free survival did not differ significantly from that in comparable
      historical controls not given THY.

PMID- 16635794
TI  - Direct comparison of umbilical cord blood versus bone marrow-derived endothelial
      precursor cells in mediating neovascularization in response to vascular ischemia.
AB  - Endothelial precursor cells (EPCs) cultured from adult bone marrow (BM) have been
      shown to mediate neovasculogenesis in murine models of vascular injury. We sought
      to directly compare umbilical cord blood (UCB)- and BM-derived EPC surface
      phenotypes and in vivo functional capacity. UCB and BM EPCs derived from
      mononuclear cells (MNC) were phenotyped by surface staining for expression of
      stromal (Stro-1, CXCR4, CD105, and CD73), endothelial (CD31, CD146, and vascular
      endothelial [VE]-cadherin), stem cell (CD34 and CD133), and monocyte (CD14)
      surface markers and analyzed by flow cytometry. The nonobese diabetic/severe
      combined immunodeficiency murine model of hind-limb ischemia was used to analyze
      the potential of MNCs and culture-derived EPCs from UCB and BM to mediate
      neovasculogenesis. Histologic evaluation of the in vivo studies included
      capillary density as a measure of neovascularization. Surface CXCR4 expression
      was notably higher on UCB-derived EPCs (64.29%+/-7.41%) compared with BM
      (19.69%+/-5.49%; P=.021). Although the 2 sources of EPCs were comparable in
      expression of endothelial and monocyte markers, BM-derived EPCs contained higher
      proportions of cells expressing stromal cell markers (CD105 and CD73). Injection
      of UCB- or BM-derived EPCs resulted in significantly improved perfusion as
      measured by laser Doppler imaging at days 7 and 14 after femoral artery ligation
      in nonobese diabetic/severe combined immunodeficiency mice compared with controls
      (P<.05). Injection of uncultured MNCs from BM or UCB showed no significant
      difference from control mice (P=.119; P=.177). Tissue samples harvested from the
      lower calf muscle at day 28 demonstrated increased capillary densities in mice
      receiving BM- or UCB-derived EPCs. In conclusion, we found that UCB and BM
      derived EPCs differ in CXCR4 expression and stromal surface markers but mediate
      equivalent neovasculogenesis in vivo as measured by Doppler flow and histologic
      analyses.

PMID- 16635795
TI  - ASBMT committee report: white paper on measurement of quality outcomes.

PMID- 16635796
TI  - Xbp1-based engineering of secretory capacity enhances the productivity of Chinese
      hamster ovary cells.
AB  - A variety of successful transcription and translation engineering strategies
      implemented during the past decade have driven the specific productivity of
      mammalian cells to an apparent limit. Restricted post-translation competence has
      since been considered the major bottleneck preventing mammalian cells from fully
      exploiting their physiologic production capacity in a biopharmaceutical
      manufacturing scenario. Through ectopic expression of the human transcription
      factor Xbp1 (X-box-binding-protein 1), evolved to manage plasma cell
      differentiation and coordinate the unfolded protein response, we have
      specifically expanded the endoplasmic reticulum and the Golgi of transgenic
      Chinese hamster ovary (CHO-K1)-derived cell lines with a resulting increase in
      overall production capacity. Xbp-1-based engineering of secretory bottlenecks was
      compatible with a variety of different promoter-product gene configurations
      suggesting that Xbp-1 induces generic production increases in CHO-K1 cell
      derivatives. Secretion engineering, illustrated here by Xbp1-based reprogramming
      of the post-translational processing machinery, provides a first insight into
      mastering a major system bottleneck which impacts biopharmaceutical manufacturing
      of secreted protein therapeutics.

PMID- 16635798
TI  - Dundee: discovering life sciences.

PMID- 16635799
TI  - Edinburgh Science Triangle: visionary initiative to serve the next generation of
      life scientists.

PMID- 16635800
TI  - Glasgow and the West of Scotland region--bioscience buds beginning to bloom.

PMID- 16635801
TI  - Antibacterial drug discovery and structure-based design.
AB  - Bacterial resistance continues to develop and pose a significant threat, both in
      hospitals and, more recently, in the community. A focus on other therapeutic
      areas by the larger pharmaceutical companies has left a shortfall in the pipeline
      of novel antibacterials. Recently, many new structures have been studied by
      structure-genomics initiatives, delivering a wealth of targets to consider. Using
      the tools of structure-based design, antibacterial discovery must exploit these
      targets to accelerate the process of drug discovery.

PMID- 16635802
TI  - Bone morphogenetic proteins and growth differentiation factors as drug targets in
      cardiovascular and metabolic disease.
AB  - Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs)
      control the development and homeostasis of multiple tissue types in many
      organisms, from humans to invertebrates. These morphogens are expressed in a
      tissue-specific manner and they signal by binding to serine-threonine kinase
      receptors, resulting in coordinated changes in gene expression that regulate the
      differentiation and development of multiple tissue types. In addition, these
      proteins are regulated post-transcriptionally through binding to several soluble
      proteins. In this review we focus on a subset of BMPs and GDFs that have been
      implicated in the pathophysiology of type 2 diabetes and cardiovascular disease.

PMID- 16635803
TI  - Progress and problems in the exploration of therapeutic targets.
AB  - Drugs exert their therapeutic effect by binding and regulating the activity of a
      particular protein or nucleic acid target. A large number of targets have been
      explored for drug discovery. Continuous effort has been directed at the search
      for new targets and more-extensive exploration of existing targets. Knowledge of
      these targets facilitates the understanding of molecular mechanisms of drugs and
      the effort required for drug discovery and target searches. Areas of progress,
      current focuses of research and development and the difficulties in target
      exploration are reviewed. The characteristics of the currently explored targets
      and their correlation to the level of difficulty for target exploration are
      analyzed. From these characteristics, simple rules can be derived for estimating
      the difficulty level of target exploration. The feasibility of predicting
      druggable proteins by using simple rules and sequence-derived physicochemical
      properties is also discussed.

PMID- 16635804
TI  - Consensus scoring for protein-ligand interactions.
AB  - This article reviews the application of consensus scoring for cases when the
      target 3D structure is known. Comparing the performance of different methods is
      not a trivial task, and it appears that consensus scoring usually substantially
      improves virtual screening performance, contributing to better enrichments. It
      also seems to improve--albeit less dramatically--the prediction of bound
      conformations and poses. The prediction of binding energies is still rather
      inaccurate and although consensus scoring generally improves these predictions,
      more development is required before it can be used for this purpose in routine
      lead optimization.

PMID- 16635805
TI  - Computational modeling of biologically active molecules using NMR spectra.
AB  - The molecular structure and NMR chemical shift information of a compound can be
      combined to form powerful models of biological activity. NMR spectral data and
      structure information can be combined on a structural template analogous to 3D
      QSAR methodology or orientation independently in spectral space. Surprisingly,
      quantitative spectrometric data-activity relationship (QSDAR) models built on
      structure templates are inferior to multi-dimensional QSDAR models built in
      spectral space. 3D-QSDAR modeling could be useful for estimating chemical
      toxicity, risk assessment of environmental contaminants and drug lead-compound
      identifications.

PMID- 16635806
TI  - Challenges for chemoinformatics education in drug discovery.
AB  - Chemoinformatics is rapidly becoming a core part of drug design informatics, yet
      the educational opportunities in the field are currently limited. This article
      reviews the academic and commercial educational programs that are available in
      chemoinformatics, considers the current challenges and takes a look at emerging
      trends, such as distance education and intensive short courses.

PMID- 16635807
TI  - New perspectives on the impact of cytochrome P450 3A expression for pediatric
      pharmacology.
AB  - Advances in the basic and clinical sciences of drug actions and safety have been
      applied almost exclusively to the largest demographic patient group--adults.
      Metabolism-dependent drug clearance is not only a primary determinant for
      obtaining efficacious drug exposure, but could also demonstrate clear age
      dependence. These concepts are exemplified by the three major human cytochrome
      P450 (CYP) 3A enzymes: CYP3A4, CYP3A5 and CYP3A7. Recent preclinical and clinical
      studies show CYP3A7 is the most abundant CYP3A enzyme in fetal liver, with a
      gradual shift towards CYP3A4 expression throughout childhood. However, the
      polymorphic nature and regulatory intricacies of CYP3A5 and CYP3A7 expression
      could cause an underappreciated contribution to interindividual variability in
      drug response and safety.

PMID- 16635808
TI  - Biological assay challenges from compound solubility: strategies for bioassay
      optimization.
AB  - Compound solubility in buffers and dimethyl sulfoxide (DMSO) has emerged as an
      important issue. Many discovery compounds have low solubility but are potentially
      valuable as leads. Unfortunately, low solubility affects bioassays by causing
      underestimated activity, reduced HTS-hit rates, variable data, inaccurate SAR,
      discrepancies between enzyme and cell assays and inaccurate in vitro ADME-Tox
      testing. Strategies for optimizing bioassays include: considering solubility in
      HTS-library design; early screening for solubility; improving storage and
      handling of DMSO stocks; optimizing dilution protocols; and ensuring that low
      solubility compounds are fully solubilized in bioassays. These approaches allow
      for adequate assessments of valuable pharmacophores for which solubility can be
      chemically optimized at a later date.

PMID- 16635809
TI  - Small organic molecules that modulate gene transcription.
AB  - Regulation of gene expression by transcription factors touches all aspects of
      human biology and often induces extreme phenotypes. Its external, precise control
      by small organic molecules represents a challenge in chemistry and biology. Here,
      we summarize recent progress in the field, together with contributions from our
      laboratory. Small-molecule modulators of transcription, including small-molecule
      transcription factors could find their use in basic biological studies and
      therapeutic intervention.

PMID- 16635810
TI  - An overview of statin-associated proteinuria.
AB  - Statins are an established therapeutic modality for the treatment of
      hypercholesterolemia. Although they generally exhibit a good efficacy and
      tolerability profile, their reputation has been tarnished as a result of reports
      of myotoxicity and, more recently, observations of proteinuria. The increased
      incidence of proteinuria with rosuvastatin was of particular concern, and raised
      questions about the renoprotective actions of statins. Different hypotheses have
      been put forward to explain the mechanisms of statin-induced proteinuria. The
      multifarious effects of statins, independent of their effects on cholesterol
      lowering, form the basis of such hypotheses. However, rosuvastatin-associated
      proteinuria is transient and reversible and even at the highest dose did not
      affect renal function after prolonged treatment. It would appear that clinically
      relevant proteinuria is not associated solely with rosuvastatin and might
      represent a minor class effect of statins with a fairly low incidence. However,
      definitive proof of this assertion will need to be provided by rigorous testing.

PMID- 16635811
TI  - Drug discovery: selecting the optimal approach.
AB  - The target-based drug discovery approach has for the past 10-15 years been the
      dominating drug discovery paradigm. However, within the past few years, the
      commercial value of novel targets in licensing deals has fallen dramatically,
      reflecting that the probability of reaching a clinical drug candidate for a novel
      target is very low. This has naturally led to questions regarding the success of
      target-based drug discovery and, more importantly, a search for alternatives.
      This paper evaluates the strengths and limitations of the main drug discovery
      approaches, and proposes a novel approach that could offer advantages for the
      identification of disease-modifying treatments.

PMID- 16635858
TI  - Thinking under fire.

PMID- 16635859
TI  - The profession of ferryman: considerations on the analyst's internal attitude in
      consultation and in referral.
AB  - Psychoanalytic consultation is an interview with a patient who will not be taken
      in treatment by the consultant analyst, but who will be sent to another, perhaps
      specifically chosen, colleague after one or more assessment sessions. This
      practice is becoming increasingly important since, besides traditional private
      relationships between consultant and patient, it is now common in many
      specialized centres affiliated to official psychoanalytical institutions. The
      author explores some fundamental aspects of the analyst's internal attitude in
      consultation: motivation to know; a 'concave' attitude to listening;
      responsibility in proposing suitable technical choices and referral to a further
      specialist; empathy and partial identification; the balance between authentic
      experience in the consultation and risks of seduction; internal links within the
      community of colleagues; the technique for sending patients on. He presents a
      clinical example, specifically aimed at reproducing the internal attitude of the
      analyst, together with the necessary work that allows a difficult patient to
      initiate psychoanalytic treatment.

PMID- 16635860
TI  - The myths of free association and the potentials of the analytic relationship.
AB  - The author challenges the traditional and still prevalent view of 'free
      association', arguing that it entails three forms of denial (also formulated in
      terms of corresponding myths): 1) denial of the patient's free agency; 2) denial
      of the patient's and the analyst's interpersonal influence; and 3) denial of the
      patient's share of responsibility for co-constructing the analytic relationship.
      That responsibility includes some degree of consideration of the analyst's needs.
      Sometimes, the patient's good judgment to that end may be reflected in what is
      automatically and mistakenly reduced to a form of 'resistance'. Attention to the
      patient's responsibility must be balanced against the effort to provide a
      uniquely safe environment for the patient's revealing of shame and anxiety-ridden
      feelings and attitudes. But the therapeutic action of psychoanalysis, ideally,
      includes the cultivation, through lived experience, of the dialectical interplay
      of self-expression, on the one hand, and caring relational engagement, on the
      other. Recognition of the patient's free agency does not preclude exploration of
      constraining structures laid down in the past. On the contrary, it deepens such
      exploration. At the same time, it opens the door to the possibility of explicit
      recognition, via challenge, criticism, or affirmation, of the patient's
      contributions to the analytic work.

PMID- 16635861
TI  - Beyond transference, countertransference, the silences and the opinion.
AB  - The author examines several works of an intersubjectivist trend, as well as
      writings by Hanly, Cavell and Bion, defending many of the named psychoanalysts'
      viewpoints. These viewpoints are expressed in the search and the struggle for
      truth, recognizing, like Popper, that truth exists but that we cannot know with
      certainty whether and when we touch upon it, only that this endless effort merits
      a lifetime's work because it is the attempt at an encounter with ourselves--the
      true encounter. The author explains the criticisms by Green of Jacobs, and
      defends the maintenance of 'a certain possible neutrality' (Eizirik). He poses
      some questions with regard to Ogden's 'third subject', considering it, among
      other aspects, from the supervisory point of view, which may demonstrate the
      existence of 'a certain possible objectivity' of the emotional conflict. He
      develops some criticisms concerning silence as an interpretative action by Ogden,
      and summarizes two case histories. Both were unconsciously attempting to
      manipulate the analyst intensely--one of them to get the analyst to intervene in
      his love life, and the other to interrupt acting out.

PMID- 16635862
TI  - Implicit memory and early unrepressed unconscious: their role in the therapeutic
      process (how the neurosciences can contribute to psychoanalysis).
AB  - The author discusses memory from the point of view of the neurosciences and
      molecular biology, proposing an integration with the psychoanalytic theory of the
      unconscious. The discovery of the implicit memory has extended the concept of the
      unconscious and supports the hypothesis that this is where the emotional and
      affective--sometimes traumatic--presymbolic and preverbal experiences of the
      primary mother-infant relations are stored. They could form the ground structure
      of an early unrepressed unconscious nucleus of the self. Identifying the
      unconscious with the memory leads to a theory about its morpho-functional
      organization. The unrepressed unconscious can be brought to the surface in
      analysis through the 'musical dimension' of the transference, characterized by
      the voice (its intonation and rhythm) and the prosody of the language. Dreams can
      symbolically transform pre-symbolic and preverbal experiences, so that they can
      be put into words and thought about even without their recollection. Dreams can
      also create images to fi ll the gap of the absence of representation which
      characterize the unrepressed unconscious. The description of a segment of
      analysis of a patient suffering from death anxiety provides a clinical
      illustration of the theories discussed. The interpretation of her voice and of
      the prosody of her language, besides the work on dreams, reproduced the emotional
      essence of the analysand's traumatic childhood experiences. This reconstruction
      enabled her to speak and think about them even without the actual recollection.

PMID- 16635863
TI  - The analyst's excitement in the analysis of perversion.
AB  - The author believes that unconscious sexual excitement in the transference and
      countertransference is an especially problematic aspect of the analysis of
      perverse character pathology and that perverse sexual gratification deserves a
      more prominent position in the clinical theory of analyzing perversion than that
      which has been assigned tacitly through analysts' routine focus on the defensive
      and destructive dynamics of perversion. He presents clinical material from the
      analysis of a perverse patient that illustrates the role of excitement in the
      transference perversion established in this analysis; and he asserts that
      gratifying perverse enactments occurring in the transference perversion can
      appear not only as conscious or unconscious excitement in the transference but
      also, at times most clearly, as the analyst's excitement. The author suggests
      that using a clinical theory that supports the analyst in understanding his
      excited responses as perverse countertransferences--i.e. evoked excitement
      complementary to the sexual component of a perverse transference--will assist him
      in locating and thinking about gratifying, perverse excitement in the
      transference where it is most usefully analyzed. Finally, he discusses some of
      the reasons why analysts might deny, suppress or otherwise avoid perverse
      countertransferences and in so doing contribute to sustaining perverse
      resistances.

PMID- 16635864
TI  - The stranger.
AB  - This work concerns a nine-year analytical experience with a patient who presented
      as a main feature an apparent inability to experience and express feelings. Right
      from the beginning the author was confronted with the question of the viability
      of analytical work, considering transference or emotional involvement in the
      absence of perceptible establishment of an affective link on the part of the
      patient. The patient never missed a session, was usually very punctual and
      presented very rich material, but the accounts of his life, everything he was
      saying, hearing and observing was manifestly deprived of any emotional meaning
      for the patient and consequently deprived of sense for the analyst. If, at the
      beginning, the question was how to communicate with the patient, after some time
      it became a problem of how to enable the patient to communicate with himself.
      Confirming an observation by Bion that the patient is the best colleague the
      analyst can have, the way forward was indicated by the patient himself. This
      article is a theoretical exercise based on this clinical experience, using
      concepts developed by Bion, Ferro and Winnicott.

PMID- 16635865
TI  - Sensory empathy and enactment.
AB  - The authors propose the concept of sensory empathy which emerges through contact
      between analyst and patient as they get in touch with an area concerning the
      primary bond. This area is not so much based on thoughts and fantasies as it is
      on physical sensations. Sensory empathy has to do with that instrument described
      by Freud as pertaining to the unconscious of any human, which enables one person
      to interpret unconscious communications of another person. The authors link this
      concept to that of enactment precisely because the latter concerns unconscious,
      early elements that fi nd in the act a fi rst meaningful expression. It involves
      both analyst and patient. In other words, the authors wish to emphasize the
      importance of the analytical process maintaining contact with that immense field
      of human interaction that can be defined as primary sensory area and which
      becomes intertwined with the evolution of affects. Clinical examples are provided
      to clarify these hypotheses.

PMID- 16635866
TI  - When a patient commits suicide: an empirical study of psychoanalytic clinicians.
AB  - Twelve psychoanalysts/psychoanalytic psychotherapists who had a patient commit
      suicide while in treatment, or shortly after leaving treatment, were interviewed
      to gain a deeper understanding of the effects of patient suicide on the
      clinician. A phenomenological research interview was used to gather data, and a
      psychoanalytic lens was used to interpret the data, generating a descriptive
      account of the experience of having a patient commit suicide. Thematic analysis
      of the transcripts yielded eight common themes associated with the clinician's
      subjective experience of having a patient suicide. The eight themes may be
      broadly grouped into three general structures: I. Traumatic loss and grief; II.
      Interpersonal relationships; and III. Professional identity concerns.

PMID- 16635867
TI  - The origins of Bion's work.
AB  - This study attempts to identify the scientific, philosophical and psychoanalytic
      origins of Bion's work, and includes an organization of these in a comprehensive
      and synthetic way with the help of a synoptic table. Investigation has revealed
      Bion's scientific orientation, fed by classical and modern authors--notably,
      Locke, Hume, Kant, Sylvester and Cayley, Poincare, Heisenberg, and the German
      Romantics. Bion was able to rescue certain transcendent aspects of human, and
      also of Freudian, knowledge that had largely fallen into neglected obscurity. He
      made an original use of new verbal expressions related to the immaterial facts of
      psychic reality, the unconscious and the id. The method involves a search for
      counterparts in reality with two kinds of evidential source: some works and their
      authors have appeared ipsis litteris in Bion's work. In those situations where
      Bion does not cite the sources, the study has been able to establish connections
      with the lengthy marginal notes which Bion left in the texts of the books from
      his library.

PMID- 16635868
TI  - Death in the afternoon.
AB  - One afternoon, a patient who had been in three-times-weekly psychoanalytic
      psychotherapy for over fi ve years with the author left the office after her
      session, drove down to the train tracks half a mile away, and sat down facing an
      oncoming train. Her suicide occurred a little over a year after 19 hijackers took
      over four passenger airplanes and fl ew two of them into the World Trade Center,
      and during the period of the massive buildup for a pre-emptive war with Iraq.
      This paper explores the very personal impact of these interlocking events of
      personal, political, and state-sponsored terrorism on the author. Interweaving
      the patient's and the author's personal struggle with the patient's overwhelming
      destructiveness--and how it ultimately failed--with the inability to stop the war
      despite the unprecedented mobilization of voices for peace across the world, it
      is a journey through the shattering impact of violence into the tentative
      discovery of a sustaining vision of hope. It explores the theme of terrorism,
      both personal and political, as a theater of violence designed to create maximum
      impact, and how fantasies of redemption, fueled and blinded by righteous
      certainty, can transmute into acts of breathtaking violence, and fi nd
      justification in their own mad logic. Through the elaboration of the patient's
      story and its impact on the author, she offers a very personal attempt to
      understand and reckon with violence and destructiveness as manifested in these
      different forms, to grasp how openings of hope and new creative possibility are
      often followed by a violent regressive backlash, and to fi nd a way to survive
      them without losing heart for the work.

PMID- 16635869
TI  - The role of pre-oedipal and oedipal factors in psychic life.
AB  - The Oedipus complex, a basic concept in Freudian theory, is an essential factor
      in the constitution of the human subject. It plays a key role in the structuring
      of the personality and in the orientation of desire. It is the oedipal triangular
      structure that precedes the pre-oedipal situation (in a logical, not
      chronological, order), and not vice versa. The oedipal structure exists before
      the infant's biological birth. It is present in the parents' desires and
      identifications, which inexorably fall upon each subject. That is why the author
      believes that it is necessary to leave behind a solipsistic reading of the
      nuclear complex of neuroses--a reading that is based solely on Oedipus's drive
      nucleus--and take a joint and comprehensive view of Laius's and Jocasta's
      histories and traumatic experiences, which were invested in their son. Among
      these three vertices, a dynamic set of forces emerges whereby a basic, original
      unconscious field phantasy is created that bears a unique narrative and an
      invisible and hermetic web made of passions and beliefs, scandals and secrets.
      This phantasy gives shape to an unrepeatable oedipal structure in each subject, a
      structure that articulates with the effects of the narcissistic and fraternal
      dynamic and may determine the subject's fate. This paper develops the following
      issues: 1) Oedipus, victimizer or victim?; 2) the generational confrontation as
      dynamic field; and 3) neuroses with a preponderance of dualistic relationships.

PMID- 16635870
TI  - Attention deficit hyperactivity disorder and trauma.

PMID- 16635871
TI  - The prevention and treatment of organizationally induced trauma.

PMID- 16635872
TI  - Do cultural differences affect training or have all analysts, across cultures,
      been trained equally since 1920?

PMID- 16635873
TI  - Time and history in psychoanalysis.

PMID- 16635874
TI  - Psychoanalytical psychotherapy for/with couples theoretical basis and clinical
      utility.

PMID- 16635875
TI  - Intersubjectivity, recognition and the problem of the negative.

PMID- 16635876
TI  - A retraction and apology. A boycott by passport.

PMID- 16635877
TI  - Pan-Dora's box. Fetishism, hysteria, and the gift of death in Die Buchse der
      Pandora (1929).

PMID- 16635902
TI  - Non-steroidal anti-inflammatory drugs request parity with Helicobacter pylori.

PMID- 16635903
TI  - Effects and outcomes after palliative surgical treatment of malignant dysphagia.

PMID- 16635904
TI  - Analysis of the acidity index and integrated intragastric acidity in 645 patients
      presenting with gastroesophageal reflux disease symptoms.
AB  - OBJECTIVE: In a recent study of patients receiving proton-pump inhibitor (PPI)
      therapy, a new parameter, the acidity index, was described as being less
      complicated to calculate and of comparable accuracy (r = 0.93) to integrated
      intragastric acidity (IA) in assessing intragastric pH control. The aim of this
      study was to correlate AI with IA using a large database of ambulatory 24-h pH
      metry studies in untreated patients presenting with gastroesophageal reflux
      disease (GERD) symptoms. MATERIAL AND METHODS: We retrospectively analyzed 645
      studies obtained from 1995 to 2001. Daytime (0800 h-2200 h), night-time (2200 h
      0800 h) and 24-h IA and AI were calculated according to age, gender and the
      presence or absence of GERD, and correlations between these parameters were
      assessed using linear regression with F-statistic values, p-values and Akaike's
      Information Criterion values. GERD was defined as total esophageal pH time <4.0,
      5 cm above the lower esophageal sphincter, for > or =4.2% of the day. IA and AI
      were calculated as follows: IA (mmol x h/l) = summation operator(acid in mmol/l
      at time "t" + acid in mmol/l at time "t - 1")/2 x ("t"-"t - 1"); AI = (%time pH <
      4-%time pH < 3) x 1+(%time pH < 3-%time pH < 2) x 10+(%time pH < 2-%time pH < 1)
      x 100 + (%time pH < 1-%time pH < 0.8) x 1000. RESULTS: Overall, the mean 24-h IA
      value was 882.0+/-820.0 mmol x h/l (daytime 392.0+/-400.0, night-time 490.0+/
      486.0). The mean 24-h AI value was 102.0+/-87.0 (daytime 86.0+/-80.0, night-time
      120.0+/-114.0, p < 0.001). The mean 24-h IA value was 1057.0+/-829.4 mmol x h/l
      (daytime 459.8+/-406.0, night-time 597.2+/-500.4, p < 0.001) in GERD patients and
      713.0+/-775.0 mmol x h/l (daytime 326.0+/-383.0, night-time 387.0+/-448.5) in non
      GERD patients (p < 0.001). The mean 24-h AI value was 122.1+/-88.1 (daytime
      101.4+/-82.5, night-time 145.3+/-120.7) in GERD patients and 83.0+/-81.0 (daytime
      71.0+/-73.9, night-time 96.4+/-102.6) in non-GERD patients (p < 0.001). Our
      statistical modeling demonstrated that the correlation between the acidity index
      and IA becomes progressively poorer with increasing values of acidity.
      CONCLUSIONS: We conclude that gastric acid production assessed by both IA and AI
      is higher during evening hours in comparison with daytime hours and the
      difference between night-time and daytime values is statistically significant. In
      addition, gastric acid production assessed by both IA and AI is significantly
      higher in GERD patients than non-GERD patients. This difference is primarily due
      to differences in nocturnal acid production. The AI correlates poorly with
      measured IA, especially at higher levels of gastric acidity. Therefore, AI is not
      an acceptable surrogate for IA in assessing gastric acid production.

PMID- 16635905
TI  - A new method for visualization of gut mucosal cells, describing the
      enterochromaffin cell in the rat gastrointestinal tract.
AB  - OBJECTIVE: Enterochromaffin (EC) cells in the gastrointestinal tract have an
      important function as regulators of secretion, motility and sensation. The EC
      cell has traditionally been described as bottle-shaped, with basally located
      stores of serotonin. Stimuli acting on the apical membrane trigger serotonin
      release, which in turn activates the subepithelial sensory nerve terminals. To
      better describe the appearance of EC cells, we developed a new method for
      visualization of mucosal cells. MATERIAL AND METHODS: The stomach, small
      intestine and large intestine were excised from Sprague-Dawley rats and then
      fixed in formalin. The organs were everted and filled with pronase solution.
      Single cells and aggregates of formalin-fixed mucosal cells were collected by
      scraping the mucosa off the muscularis mucosa. EC cells were visualized by
      staining for immunoreactivity against serotonin. RESULTS: EC cells with luminal
      extensions and very long (up to 80 microM) basally located axon-like extensions,
      sometimes connecting to neuron-like structures, were found. Other EC cells had no
      or only short and blunt basal extensions. Dividing serotonin-containing EC cells
      were also seen. CONCLUSIONS: These findings could make an important contribution
      towards furthering our understanding of EC cell function in gastrointestinal
      physiology. This new method can also readily be used to give better visualization
      of the morphology of other mucosal cells.

PMID- 16635906
TI  - Evaluation of the necessity of induction for lactose-[15N, 15N]-ureide to study
      the colonic ammonia metabolism.
AB  - OBJECTIVE: Stable isotope labelled glycosyl ureides have been described as non
      invasive markers for measurement of gastrointestinal processes. Lactose-[13C]
      ureide is used for the evaluation of orocaecal transit time (OCTT), whereas
      lactose-[15N, 15N]-ureide is used to study the fate of the NH3 metabolism in the
      colon. Induction with unlabelled lactose ureide is necessary for the
      determination of the OCTT. In the present study, the effect of a preceding
      induction on the fate of 15NH3 in the colon was evaluated. MATERIAL AND METHODS:
      Ten healthy volunteers performed two tests: the first test without induction, the
      second test one week later with induction, i.e. administration of 1 g lactose
      ureide the evening before the test. Each test consisted of a fractionated 24-h
      urine collection after the subjects had received a pancake test meal labelled
      with 75 mg lactose-[15N, 15N]-ureide. All samples were analysed for [15N]-content
      by combustion IRMS (isotope ratio mass spectrometry) and results were expressed
      as a percentage of the administered dose. RESULTS: No significant differences
      were found in the percentage dose 15N excreted in the different urine fractions
      between the test without and with preceding induction. The cumulative excretion
      rates of the 15N-isotope after 24 h were 44.35% without induction and 44.27% with
      induction. CONCLUSIONS: The results in this study show that predosing with
      unlabelled lactose ureide is unnecessary for the evaluation of the ammonia
      metabolism in the colon by means of lactose-[15N, 15N]-ureide.

PMID- 16635907
TI  - Home parenteral nutrition in Denmark in the period from 1996 to 2001.
AB  - OBJECTIVE: Home parenteral nutrition (HPN) has been provided to patients with
      intestinal failure in Denmark since 1970. The results of a national survey
      comprising a well-defined cohort receiving treatment with HPN in Denmark in the
      period from 1996 to the end of 2000 are presented, including data on incidence,
      prevalence, patient characteristics and complications of HPN treatment. MATERIAL
      AND METHODS: HPN was given to 202 patients (115 F, 87 M) 34% with short-bowel
      syndrome due to inflammatory bowel disease, 26% with cancer, 22% with surgical
      complications and 19% with other causes, for a total of 410 catheter years.
      RESULTS: At the end of 2000, the prevalence of HPN in Denmark was 19.2 per
      million, and the average annual incidence was 5.0 per million per year over the 5
      year period. The incidence rates of catheter-related bacteraemia and thrombosis
      were 0.48 and 0.02 episodes per catheter year, respectively. The average catheter
      lasted 1.5 years. Venous inaccessibility was never encountered. The 5-year
      mortality was 25% (n = 51). However, only six deaths were related to HPN. Three
      patients died of HPN-related liver failure, two died of catheter-related sepsis
      and one patient died of an embolus induced by a catheter thrombus. CONCLUSIONS:
      Since its introduction in 1970 in Denmark, HPN has evolved from an experimental
      approach to a standardized therapy for patients with intestinal failure. Although
      HPN morbidity is increasing slightly compared with that reported in earlier
      surveys, HPN-induced mortality is still less than 1% per year.

PMID- 16635909
TI  - Functional polymorphism of the NFKB1 gene promoter is not relevant in
      predisposition to celiac disease.
AB  - OBJECTIVE: The nuclear factor (NF)-kappaB is one of the pivotal regulators of
      autoimmunity and inflammation, which has been shown to be activated in the
      inflamed mucosa of patients with celiac disease (CD). Recently, in the NFKB1 gene
      promoter region, a common insertion/deletion (-94ins/delATTG) polymorphism
      located between two putative key promoter regulatory elements was described. The
      aim of this study was to investigate the contribution of the -94ins/delATTG NFKB1
      gene promoter functional variant to CD genetic predisposition. MATERIAL AND
      METHODS: A case-control cohort comprising 478 patients with CD and 711 healthy
      controls as well as a panel of 196 celiac families was genotyped for the
      94ins/delATTG NFKB1 polymorphism, using a polymerase chain reaction (PCR) method
      combined with fluorescence technology. RESULTS: We found no statistically
      significant differences between CD patients and controls when the -94ins/delATTG
      genotype and allele distributions were compared. Accordingly, the familial
      analysis did not reach statistically significant deviation in the transmission of
      -94ins/delATTG alleles to the affected offspring. CONCLUSIONS: From these
      results, it could be suggested that the -94ins/delATTG NFKB1 polymorphism does
      not play a major role in CD susceptibility.

PMID- 16635908
TI  - Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac
      intestinal mucosa and intestinal cell lines.
AB  - OBJECTIVE: Little is known about the interaction of gliadin with intestinal
      epithelial cells and the mechanism(s) through which gliadin crosses the
      intestinal epithelial barrier. We investigated whether gliadin has any immediate
      effect on zonulin release and signaling. MATERIAL AND METHODS: Both ex vivo human
      small intestines and intestinal cell monolayers were exposed to gliadin, and
      zonulin release and changes in paracellular permeability were monitored in the
      presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal
      rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by
      immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression
      was evaluated by real-time polymerase chain reaction (PCR). RESULTS: When exposed
      to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in
      the cell medium with subsequent zonulin binding to the cell surface,
      rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein
      interaction, and increased monolayer permeability. Pretreatment with the zonulin
      antagonist FZI/0 blocked these changes without affecting zonulin release. When
      exposed to luminal gliadin, intestinal biopsies from celiac patients in remission
      expressed a sustained luminal zonulin release and increase in intestinal
      permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from
      non-celiac patients demonstrated a limited, transient zonulin release which was
      paralleled by an increase in intestinal permeability that never reached the level
      of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure
      caused down-regulation of both ZO-1 and occludin gene expression. CONCLUSIONS:
      Based on our results, we concluded that gliadin activates zonulin signaling
      irrespective of the genetic expression of autoimmunity, leading to increased
      intestinal permeability to macromolecules.

PMID- 16635910
TI  - Screening of tumor necrosis factor receptor-associated factor 6 as a candidate
      gene for inflammatory bowel disease.
AB  - OBJECTIVE: The two forms of inflammatory bowel disease (IBD), Crohn's disease
      (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of
      unfavorable genetic and exogenous factors. During a genome-wide linkage study of
      IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further
      confirmed upon fine density mapping. This chromosomal region contains a
      functional IBD candidate gene coding for tumor necrosis factor receptor
      associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive
      immunity as well as bone homeostasis. MATERIAL AND METHODS: Using denaturing high
      performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon
      intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially
      screened; this material comprised 20 CD, 39 UC and 36 mixed families. RESULTS: No
      nucleotide changes in the coding sequence of TRAF6 were detected, but a single
      base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7
      thymines, respectively) in intron 3 was identified. However, examination of an
      extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy
      blood donors failed to show any association with this 7T/8T variation and IBD,
      nor was this polymorphism related to specific clinical features in IBD.
      CONCLUSIONS: Our study tends to exclude a good positional and functional
      candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea
      that the function of TRAF6 is important enough not to permit structural
      alterations of this mediator.

PMID- 16635911
TI  - Diagnostic challenge of hyper-IgD syndrome in four children with inflammatory
      gastrointestinal complaints.
AB  - OBJECTIVE: Hyper-IgD syndrome (HIDS) is a rare autosomal recessive disease
      characterized by recurrent fever, lymphadenopathy, diarrhoea, abdominal pain,
      headache, arthralgia and skin rash. Abdominal symptomatology may mimic
      inflammatory bowel disease. We report on four patients with HIDS who had been
      previously investigated for Crohn's disease (CD). The levels of IgD were measured
      in a series of patients with CD to evaluate the specificity of this assay in the
      differential diagnosis between the two conditions. MATERIAL AND METHODS:
      Diagnosis of HIDS was based on clinical criteria as well as immunological or
      genetic data. IgD levels were measured in the four subjects affected by HIDS, in
      59 patients with CD and in a group of 160 healthy controls. RESULT: All patients
      underwent a variety of gastroenterological investigations because inflammatory
      bowel disease was suspected. Ultrasonography was pathologic in all the patients,
      showing enlargement of mesenteric lymph nodes. Abdominal leucocyte scintigraphy
      displayed diffuse signals of mild to moderate degree. IgD and IgA levels were
      elevated in three out of four patients. No difference in IgD values was found in
      CD patients as compared to the control group. CONCLUSIONS: Gastrointestinal
      complaints associated with recurrent fever and mesenteric adenopathy warrant
      genetic investigation for HIDS, in order to avoid unnecessary invasive
      investigations and treatment.

PMID- 16635912
TI  - Incidence of inflammatory bowel disease in Primorsko-goranska County, Croatia,
      2000-2004: A prospective population-based study.
AB  - OBJECTIVE: It has been suggested that the incidence of inflammatory bowel disease
      (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is higher
      in northern than in southern Europe. Recent epidemiological studies showed the
      loss of the previously described geographical north-south gradient. The aim of
      this study was to investigate the incidence of UC and CD in Primorsko-goranska
      County, Croatia. MATERIAL AND METHODS: In the period 1 January 2000 to 31
      December 2004 (5 years) all new patients diagnosed with IBD were prospectively
      identified according to a standard protocol for case ascertainment and
      definition. A total of 178 residents (81 F, 97 M) were newly diagnosed as having
      IBD during the study period. Of these, 70 had UC and 100 CD. Eight patients had
      indeterminate IBD. The data on patients were collected using a data form
      completed by gastroenterologists. RESULTS: Annual age-standardized incidence
      rates were 4.3/10(5) (95% CI 2.6-6.0) for UC and 7.0/10(5) (95% CI 3.4-10.6) for
      CD. The highest incidence rate was observed in the age group 35-44 years for UC
      and the 25-34 years age group for CD. The incidence of IBD was higher in the
      urban than in the rural population, with the exception of on the islands.
      CONCLUSIONS: The incidence of IBD was higher than previously observed in Croatia.
      Our results suggest that CD incidence rates in the northern coastal part of
      Croatia are currently comparable with those reported in northern Europe.

PMID- 16635913
TI  - Geographical clustering and maintained health in individuals harbouring the
      mutation for Greenland familial cholestasis: A population-based study.
AB  - OBJECTIVE: Cholestasis Familiaris Groenlandica, a severe variant of progressive
      familial intrahepatic cholestasis type 1 (Byler disease), carries an autosomal
      recessive trait, and the mutation has been located. The disease is relatively
      common among Inuit in East Greenland. The aim of the study was to assess the
      carrier frequency and the possible impact on health in populations in East
      Greenland. MATERIAL AND METHODS: A population-based study comprising 324 Inuit
      and non-Inuit subjects, aged 50-69 years, living in the Ammassalik district of
      East Greenland was carried out to analyse the presence of the mutation on ATP8B1
      at 18q21. Bilirubin and gamma-glutamyl transpeptidase levels in serum were
      measured, a physical examination was performed, which included body height and
      weight, and calculation of BMI. RESULTS: The participation rate was 96%. None of
      the subjects was homozygous and 12% of Inuit were heterozygous for the mutation.
      Harbouring the mutation did not influence height (p = 0.26), weight (p = 0.89),
      BMI (p = 0.65), frequency of self-reported disease (p = 0.17), or differ with
      gender (p = 0.57). A marked geographical clustering was found (p = 0.002) and
      heterozygocity for the mutation varied from 5% in a southern to 23% in a northern
      settlement where 1 out of 75 children could be calculated to have the disease. A
      physical investigation identified none with jaundice or signs of liver disease.
      Bilirubin and gamma-glutamyl transpeptidase levels in serum were lower among
      mutation-positive compared with mutation-negative Inuit. CONCLUSIONS:
      Heterozygosity for Greenland familial cholestasis is common among the Inuit in
      East Greenland but it is not a risk factor for disease in the carrier.

PMID- 16635914
TI  - Determinants of the renin-angiotensin-aldosterone system in cirrhosis with
      special emphasis on the central blood volume.
AB  - OBJECTIVE: Several studies have shown activation of the renin-angiotensin
      aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have
      several determinants, the system is often considered a surrogate marker of
      effective hypovolaemia. In this study we investigated the activity of the RAAS
      and its potential determinants with special focus on the central and arterial
      blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class
      A/B/C: 19/41/29) and 32 controls were included in the study. All were given a
      haemodynamic examination with measurement of determinants of the RAAS, including
      the CBV. Circulating plasma renin concentrations were measured using an
      immunoradiometric assay. RESULTS: Arterial renin concentrations were
      significantly higher in the patients than in the controls (p < 0.003). Plasma
      renin correlated significantly with several indicators of liver dysfunction and
      splanchnic and systemic haemodynamics (r = - 0.56-0.55), but only weakly with CBV
      (r = - 0.25, p < 0.02). In a multivariate regression analysis, plasma renin was
      determined by serum sodium, alkaline phosphatases and systolic blood pressure (p
      < 0.04 to p < 0.001). CONCLUSIONS: CBV correlates weakly with circulating renin,
      and activation of the RAAS can therefore only partly be considered as an
      indicator of central hypovolaemia. Mechanisms other than central hypovolaemia
      relating to the liver disease and portal hypertension contribute significantly to
      the RAAS activation.

PMID- 16635915
TI  - Morbidity and mortality in liver diseases in Sweden 1969-2001 in relation to
      alcohol consumption.
AB  - OBJECTIVE: In Sweden, there is stable or slightly increased total alcohol
      consumption but a decrease in mortality in liver disease. The aim of the study
      was to determine the temporal relation between alcohol-related liver disease
      morbidity and mortality and type of alcohol beverage consumption. MATERIAL AND
      METHODS: Data on patients with liver disease from the Swedish Hospital Discharge
      Register and from the Causes of Death Register between 1969 and 2001 were
      analysed. Data on the registered sales of the different beverages were taken from
      the Swedish State Monopoly. RESULTS: Liver disease mortality increased from 1969
      to 1976, coinciding with the increase in sales of spirits. Both mortality and
      spirits sales decreased thereafter, whereas there was no decrease in beer or wine
      sales. Hospitalization rates were reduced after 1987. Depending on age and
      gender, there was a 30-80% 5-year mortality rate following discharge. Among men,
      but not among women, differences in the alcohol and non-alcohol-related liver
      diagnoses in the Hospital Discharge Register and in the Cause of Death Register
      were sometimes recorded in the same patient. CONCLUSIONS: There was a reduction
      in hospitalization rates and mortality in liver diseases, and the reduction in
      mortality in liver diseases in Sweden from 1969 to 2001 seems to be associated
      with sales of spirits. Patients hospitalized for liver disease have a poor
      prognosis. There were difficulties in differentiating between alcohol and non
      alcohol liver diseases.

PMID- 16635916
TI  - Prognosis, with evaluation of general biochemistry, of liver disease in
      lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome).
AB  - OBJECTIVE: To investigate the prognosis of liver disease in Aagenaes syndrome
      (lymphoedema cholestasis syndrome 1 (LCS1)), which is an autosomal recessive
      inherited syndrome consisting of neonatal cholestasis with intermittent
      cholestatic episodes in childhood into adulthood and development of lymphoedema.
      Forty Norwegian patients are known to have this condition, 25 of whom are alive.
      A clinical description of the liver disease is supplied with a case-control
      study. MATERIAL AND METHODS: In this paper we review the course of the liver
      disease in the Norwegian cohort of patients and present results from a case
      control study in the patients above 10 years of age. The case-control study was
      performed on 15 patients without clinical cholestasis (itching and sometimes
      jaundice) at the time of the study. An evaluation of 11 patients above 15 years
      of age without chronic biochemical cholestasis (increased alkaline phosphatase
      (ALP), gamma-glutamyl transferase (GGT) and/or serum bile acids) was also carried
      out. For each patient one randomly identified control person was included (15 in
      one study, 11 in the other). RESULTS: Cirrhosis with either transplantation or
      death in infancy or early childhood occurred in six patients; slowly developing
      cirrhosis occurred in three patients. Two patients may be in the process of
      developing cirrhosis. Significantly increased ALP and GGT levels were found in
      patients with normal liver biochemistry in the preceding years when compared with
      the case control group. Additionally, albumin was found to be lower in older
      patients. CONCLUSIONS: Compared with that for other types of hereditary neonatal
      cholestasis, patients with LCS1 have a relatively good prognosis. More than 50%
      can expect a normal life span.

PMID- 16635917
TI  - Immune status and inflammatory response differ locally and systemically in severe
      acute pancreatitis.
AB  - OBJECTIVE: Acute pancreatitis (AP) is an inflammatory disorder that develops a
      complex cascade of immunological events. The local and systemic immune status and
      inflammatory response might contribute to the understanding of underlying
      pathophysiological mechanisms and potential treatment. MATERIAL AND METHODS:
      Severe AP was induced by intraductal perfusion of 5% sodium taurodeoxycholate in
      rats. mRNA expression of cytokines and chemokines was determined by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and NF-kappaB activation was
      assessed by electrophoretic mobility shift assay in fresh pancreatic acini and
      circulating monocytes 1, 3, 6 or 9 h after sham operation, induction of AP or N
      acetylcysteine (NAC) pretreatment. Flow cytometry was performed on cells obtained
      from the peripheral blood. RESULTS: An inverse relationship in pancreatic and
      circulating monocytic NF-kappaB activation was detected 6 and 9 h after induction
      of AP. NAC further suppressed monocytic NF-kappaB activation induced by AP as
      seen 9 h after induction of AP. A marked constitutive increase in the expression
      of IL-6, CINC and MCP-1 was seen in pancreatic acini, whereas no change in mRNA
      expression of inflammatory mediators was observed in circulating monocytes 6 h
      after induction of AP. Flow cytometry further confirmed the altered function of
      circulating monocytes. CONCLUSIONS: The different immune status and inflammatory
      response in the pancreas and circulating monocytes improve the understanding of
      the mechanisms by which systemic inflammatory response syndrome (SIRS) and
      multiple organ dysfunction syndrome (MODS) develop in severe AP. A potential
      therapeutic approach could be to restore the functional capacity of the immune
      system in AP. The use of an NF-kappaB inhibitor, preferentially reaching the
      local inflammatory foci, could be a potential future way of intervention.

PMID- 16635918
TI  - The Norwegian Gastronet project: Continuous quality improvement of colonoscopy in
      14 Norwegian centres.
AB  - OBJECTIVE: The burden on colonoscopy capacity is considerable and expected to
      increase further as colorectal cancer screening programmes gain a foothold in
      Europe. In this situation, it is particularly important to evaluate the quality
      of the service given. In this article we present our first year of experience
      with a quality network of endoscopy centres in Norway (Gastronet). MATERIAL AND
      METHODS: A questionnaire focusing on caecal intubation rate and pain was
      completed by the endoscopist (on site) and patient (on the day after the
      examination). Fourteen centres participated with registration of 7370
      colonoscopies by 73 endoscopists. RESULTS: There was 100% endoscopist
      participation, 87% coverage of colonoscopies and an estimated 76% questionnaire
      coverage of the patient population. Overall caecal intubation rate was 91%, range
      83% to 97% between centres (p < 0.001). Patients reporting severe pain during
      colonoscopy differed from 2 to 24% between centres (p < 0.001). Variations could
      only partly be explained by differences in procedure practice (sedation, CO2
      insufflation). For individual endoscopists, improvement after feedback on
      performance was restricted to the group of endoscopists having contributed with
      only 50-99 registered colonoscopies. CONCLUSIONS: In quality assurance programmes
      we recommend a limited number of variables for registration in order to secure
      high compliance by endoscopists and patients. One year of experience with
      Gastronet disclosed a satisfactory overall caecal intubation rate, but
      considerable variation between centres in practice and ability to offer painless
      colonoscopy. This suggests a need for formal, centralized training of
      colonoscopists or the development of quality standards for colonoscopy training
      and practice.

PMID- 16635919
TI  - Comparison of the characteristics of submucosal injection solutions used in
      endoscopic mucosal resection.
AB  - OBJECTIVE: Submucosal injection is used to prevent complications, such as
      perforation, during endoscopic mucosal resection (EMR). Since injection of normal
      saline produces mucosal elevation of short duration, repeated injection is needed
      for extensive resection. To overcome this limitation, various submucosal
      injection solutions have been developed but there are few data comparing their
      efficacy. This study was therefore conducted to compare the physical and chemical
      properties and the duration of mucosal elevation of various submucosal injection
      solutions. MATERIAL AND METHODS: A fresh transverse colon specimen acquired from
      a mongrel was used. Experiments were repeated four times. To compare the efficacy
      of mucosal elevation, 1 ml of each solution was injected into the submucosa: 0.9%
      NaCl, 20% mannitol, 0.1% sodium hyaluronate, 0.3% hydroxypropyl methylcellulose
      (HPMC), and 2% fibrinogen. Physical and chemical properties such as viscosity and
      osmolarity were compared. RESULTS: The heights of initial mucosal elevations were
      6.52+/-0.26 mm, 6.87+/-0.05 mm, 6.92+/-0.09 mm, 6.90+/-0.08 mm, and 6.90+/-0.08
      mm for normal saline, mannitol, sodium hyaluronate, HPMC, and fibrinogen,
      respectively. Whereas injection of normal saline took about 20 min and mannitol
      about 30 min for the initial elevation to be reduced to more than half the
      initial height, it took more than 60 min for all the other agents. A correlation
      was found between the duration of mucosal elevation and viscosity but not with
      osmolarity. CONCLUSIONS: The mucosal elevation lasted longer with sodium
      hyaluronate, HPMC, and fibrinogen than with mannitol or normal saline, and this
      seems to be due to the viscosity rather than the osmolarity of each solution.

PMID- 16635920
TI  - Ascites as the first manifestation of polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that affects
      numerous organs, particularly the digestive tract (33-52% of cases). However,
      isolated ascites has rarely been described in patients with PAN. We observed a
      patient who had developed ascites revealing PAN, and because of suspected
      malignancy laparotomy and abdominal surgery were performed, including systematic
      total abdominal hysterectomy, bilateral salpingo-oophrectomy, submesocolic
      omontectomy and appendicectomy. Macroscopic examination revealed a nodule
      involving the left ovary, while histological examination of biopsy specimens
      demonstrated characteristic damage of necrotizing vasculitis involving the
      appendix, omentum, uterus, fallopian tubes and right ovary, consistent with PAN.
      The patient had a favourable outcome of clinical manifestations related to PAN
      after initiation of combined therapy of prednisone and cyclophosphamide. Our case
      report therefore reinforces the possibility of an unusual presentation of PAN. As
      ascites may precede other signs of PAN, we suggest that when unexplained ascites
      is noted an evaluation for misdiagnosed vasculitis should be carried out,
      including a search of the constitutional symptoms (e.g. fever, weight loss).
      Patients undergoing laparoscopy for peritoneal involvement of unknown origin
      should also have tissue specimens taken for pathologic studies, notably to
      exclude an underlying vasculitis.

PMID- 16635921
TI  - Morbus Wilson: Case report of a two-year-old child as first manifestation.
AB  - Morbus Wilson, or Wilson's disease, is a genetic disease of copper metabolism.
      Usually the disease is detected when the first clinical symptoms appear,
      generally not before 5 years of age. This case report shows that the disease can
      be detected much earlier if abnormal laboratory findings in the patient's history
      prompt further investigations.

PMID- 16635922
TI  - Multiple food hypersensitivity as a cause of refractory chronic constipation in
      adults.
AB  - Chronic constipation that is unresponsive to laxative treatment is a severe
      illness, but children unresponsive to laxatives have been successfully treated
      with an elimination diet. We report the first cases of refractory chronic
      constipation caused by food hypersensitivity in adults. Four patients with
      refractory constipation who were unresponsive to high doses of laxatives were put
      on an oligo-antigenic diet and underwent successive double-blind, placebo
      controlled, food challenges (DBPFC). Routine laboratory tests, immunological
      assays, colonoscopy, esophago-gastroduodenoscopy and rectal and duodenal
      histology were performed. While on an elimination diet, bowel habits normalized
      in all patients and a DBPFC challenge triggered the reappearance of constipation.
      In comparison with another 13 patients with refractory constipation unresponsive
      to the elimination diet, observed over the same period, the patients with food
      hypersensitivity-related constipation had the following characteristics: longer
      duration of illness (p < 0.03), lower body mass index (p < 0.03), higher
      frequency of self-reported food intolerance (p < 0.01), higher frequency of
      nocturnal abdominal pain and anal itching (p < 0.01). In patients with food
      hypersensitivity, hemoglobin concentrations and peripheral leukocytes were lower
      than those in controls (p < 0.03). The duodenal and rectal mucosa histology
      showed lymphocyte and eosinophil infiltration, and the duodenal villi were
      flattened in two cases. In adult patients, refractory chronic constipation may be
      caused by food hypersensitivity and an elimination diet is effective in these
      subjects.

PMID- 16635923
TI  - Jaundice of unknown origin: Remember zoonoses!
AB  - Zoonotic diseases are randomly remembered in the differential diagnosis of
      jaundice of unknown origin. We present four characteristic cases of jaundice
      attributed to brucellosis and Coxiella burnetii infection and discuss the various
      pathogenetic pathways implicated in each case. We present a brief review of the
      relevant literature and, in an era of increasing subspecialization, underline the
      importance of viewing the "whole picture".

PMID- 16635924
TI  - The treatment environment.

PMID- 16635925
TI  - Do personality traits predict first onset in depressive and bipolar disorder?
AB  - The aim was to investigate whether personality traits predict onset of the first
      depressive or manic episode (the vulnerability hypothesis) and whether
      personality might be altered by the mood disorder (the scar hypothesis). A
      systematic review of population-based and high-risk studies concerning
      personality traits and affective disorder in adults was conducted. Nine cross
      sectional high-risk studies, seven longitudinal high-risk studies and nine
      longitudinal population-based studies were found. Most studies support the
      vulnerability hypothesis and there is evidence that neuroticism is a premorbid
      risk factor for developing depressive disorder. The evidence for the scar
      hypothesis is sparse, but the studies with the strongest design showed evidence
      for both hypotheses. Only few studies of bipolar disorder were found and the
      association between personality traits and bipolar disorder is unclear.
      Neuroticism seem to be a risk factor by which vulnerable individuals can be
      identified, thus preventing the development of depressive disorder. A connection
      between personality traits and development of bipolar disorder, and evidence of a
      personality-changing effect of affective episodes need to be further
      investigated.

PMID- 16635926
TI  - The Psychiatric Out-Patient Experiences Questionnaire (POPEQ): data quality,
      reliability and validity in patients attending 90 Norwegian clinics.
AB  - The aim of this study was to develop and evaluate the Psychiatric Out-Patient
      Experiences Questionnaire (POPEQ). The instrument was developed following a
      literature review, patient interviews and pre-testing of questionnaire items. The
      POPEQ was administered as part of a postal survey of 15,422 adult outpatients
      attending Norwegian clinics; 6677 (43.3%) patients responded to the
      questionnaire. Items had low levels of missing data. Factor analysis showed that
      11 widely applicable items contribute to a measure of overall experiences. Sub
      dimensions include clinician interaction (six items) information (two items) and
      outcomes (three items). Item-total correlations ranged from 0.5 to 0.8.
      Cronbach's alpha and test-retest reliability estimates exceeded the criterion of
      0.7; the majority were over 0.8 and total scores over 0.9. Construct validity was
      supported by the results of 128 tests. The POPEQ includes important aspects of
      patient experience for psychiatric outpatients and has excellent evidence for
      reliability and construct validity. The instrument is recommended for the
      measurement of psychiatric outpatient experiences.

PMID- 16635927
TI  - Time-trends in method-specific suicide rates compared with the availability of
      specific compounds. The Danish experience.
AB  - Restriction of means for suicide is an important part of suicide preventive
      strategies in different countries. All suicides in Denmark between 1970 and 2000
      were examined with regard to method used for suicide. Overall suicide mortality
      and method-specific suicide mortality was compared with official information
      about availability of medical compounds (barbiturates, benzodiazepines,
      analgesics, antidepressants) and carbon monoxide in vehicle exhaust and household
      gas. Restrictions on the availability of carbon monoxide, barbiturates and
      dextropropoxyphen was associated with a decline in the number of suicides by self
      poisoning with these compounds. Restricted access occurred concomittantly with a
      55% decrease in suicide rate.

PMID- 16635928
TI  - Normative data for the Multidimensional Anxiety Scale for Children (MASC) in
      Swedish adolescents.
AB  - The Swedish translation of a new scale developed for childhood and adolescent
      anxiety, the Multidimensional Anxiety Scale for Children (MASC), was studied
      regarding reliability and convergent validity and to obtain norms in a general
      population. Four hundred and five adolescents, reasonably representative of
      Swedish adolescents, were asked to rate their anxiety symptoms on the MASC. In
      order to study the convergent validity, they also rated their depressive symptoms
      on the Children's Depression Inventory (CDI), their attitude to their body on the
      Body Esteem Scale for Adolescents and Adults (BESAA) and filled in demographical
      data on themselves. The MASC showed adequate internal consistency both for the
      whole scale (alpha = 0.87) and for subscales (range 0.64-0.84). The scale showed
      convergent validity through a moderate correlation with the CDI (r=0.400,
      P=0.0001) and the BESAA (r= - 0.29, P=0001). Girls scored higher (mean = 38.9)
      than boys (mean = 31.9) on the MASC total score (t(385) = 5.14, P=0.0001) and on
      the subscales, except Harm avoidance. Using the MASC as a general screen for
      anxiety, scores of 48 for boys and 56 for girls using MASC total scores, or
      scores of 15 for boys and 17 for girls using the Anxiety Disorders Index could be
      employed (both representing the 90th percentiles). The MASC appears to be a
      reliable and valid scale both on the global and on the subscale level.

PMID- 16635929
TI  - Insight in schizophrenia: a review.
AB  - The issue of insight in schizophrenia must be assumed to be one of the most
      important aspects of the clinical examination. Comprehensive studies have shown
      that between 50% and 80% of all patients suffering from schizophrenia do not
      believe that they have a disorder. In recent years, poor insight in schizophrenia
      has been the subject of increasing interest, as manifested in a number of studies
      discussed in the present review. Some of these studies focus on insight
      correlated to various parameters such as psychopathology, neuropsychology,
      clinical relevance and compliance. Other studies refer to more theoretical
      implications, among these the issue of defining the concept of insight: whether
      insight can be seen as a "primary" phenomenon in schizophrenia, and whether
      insight may be graduated, dimensioned or increased. Several authors have
      developed rating scales in an attempt to obtain a measure for the degree or
      dimension of insight. Here, the range of parameters employed gives an excellent
      impression of the complexity of the concept of insight. In the concluding
      discussion, a phenomenological aspect is brought in, in an attempt to place the
      concept of insight in relation to disturbances of the self in schizophrenia and
      to primary symptoms in schizophrenia, amongst these autism.

PMID- 16635930
TI  - The long-term level of functioning in patients admitted for psychotic disorders
      with and without substance abuse.
AB  - The main objective of this study was to compare life skills between psychotic
      patients with substance abuse problems and psychotic patients without substance
      abuse problems. This is a cross-sectional study of 48 patients (26 inpatients and
      22 outpatients) in a clinic for early intervention in psychosis. Patients were
      grouped into two categories based on if they had a substance abuse problem or
      not. Twenty-one (43.8%) had a substance abuse problem and 27 (56.2%) had not. We
      used several scales to measure substance abuse and the Life Skills Profile to
      measure aspects of functioning. A parametric test (t-test) was used to compare
      continuous variables. A non-parametric chi-square test was used to compare
      frequencies. The self-care subscore and the non-turbulence subscore were higher
      in the group with psychosis alone. These results were not significant controlling
      for age. The social contact subscore, the communication subscore, the
      responsibility subscore and the Life Skills Profile total score did not differ
      significantly between the groups. The abusers did not differ from the non-abusers
      in functioning in any area measured.

PMID- 16635931
TI  - Internalizing disorders in child psychiatric patients across time: diagnoses and
      causes for referral.
AB  - With regard to internalizing disorders we wanted to describe: 1) a possible
      change in diagnoses over time; 2) a possible corresponding change in causes for
      referral; 3) correspondence of hospital diagnosis with causes for referral. For
      70 randomly selected records/year (n=560), referral papers were examined and
      compared with register-data on all 8-13-year-old children examined in the study
      period (1995-2002). The hospital-based frequency increased for depressive
      disorders and obsessive-compulsive disorder (OCD) and decreased for anxiety
      disorders. A corresponding increase occurred for depressive and OCD symptoms as
      cause for referral. Agreement between referral causes and subsequent clinical
      diagnoses was modest. In most cases (68%) referred for internalizing symptoms, a
      clinical diagnosis within the internalizing spectrum was given. The increase in
      the diagnoses of depressive disorder and OCD seems partly due to an increase in
      patients referred for these disorders. Referrers identify internalizing disorders
      reliably but child psychiatric examination leads to more precise diagnoses.

PMID- 16635932
TI  - Antipsychotic medication and length of stay at a psychiatric maximum-security
      unit in Norway (1987-2000).
AB  - The aim of this study was to evaluate psychopharmacological treatment and the
      length of stay (LOS) of patients with schizophrenia in a maximum-security
      psychiatric unit. Data were collected from the hospital files of 82 consecutively
      admitted patients with schizophrenia who were both admitted and discharged
      between the years 1987 and 2000. Psychotropic medication and LOS at the time of
      discharge were registered. Ninety-five per cent of the patients received
      antipsychotic medication. Zuclopenthixol was the most frequent medication, given
      to 43% of the patients. Antipsychotic polypharmacy was found in 20% of the cases.
      Twenty-seven per cent of the patients were medicated with doses above the
      recommended therapeutic dose range. During the study period, there was no change
      in the administration and number of psychotropics, but there was an increase in
      the dosage of antipsychotics. However, LOS was unchanged during the same time.
      This supports other findings, which suggest that there is no clinical benefit of
      higher antipsychotic dosage. It is suggested that an optimized medication
      practice could yield beneficiary effects, not only for schizophrenic symptoms,
      but also for violence in schizophrenic patients.

PMID- 16635933
TI  - Evaluation of family therapy.
AB  - Because children of mentally disordered parents have an increased risk of
      becoming subjects of mental disorder and psychological problems, adult psychiatry
      has increasingly paid attention to the patients' parental skills. This study
      includes 31 families with children younger than 18 years of age where the parents
      were admitted to family therapy in an open psychiatric ward. The average number
      of sessions was seven, and the diagnoses of severe stress and of adjustment
      disorder were the most common. The aim of the study was to measure changes in the
      family climate during the period of therapy. The instrument used was the Family
      Environment Scale (FES), a self-rating questionnaire that measures the parents'
      experience of family environment. The change of family environment is related to
      its influence on children's well-being and development. The study finds that
      family therapy has resulted in positive changes of the parents' experience of the
      family climate.

PMID- 16635934
TI  - Effects of a psychiatric intensive care unit in an acute psychiatric department.
AB  - Psychiatric acute units use different levels of segregation to satisfy needs for
      containment and decrease in sensory input for behaviourally disturbed patients.
      Controlled studies evaluating the effects of the procedure are lacking. The aim
      of the present study was to compare effects in acutely admitted patients with the
      use of a psychiatric intensive care unit (PICU) and not in a psychiatric acute
      department. In a naturalistic study, one group of consecutively referred patients
      had access only to the PICU, the other group to the whole acute unit. Data were
      obtained for 56 and 62 patients using several scales. There were significant
      differences in reduction of behaviour associated with imminent, threatening
      incidents (Broset Violence Checklist), and actual number of such incidents (Staff
      Observation Aggression Scale-Revised) in favour of the group that was treated in
      a PICU. The principles of patient segregation in PICUs have favourable effects on
      behaviours associated with and the actual numbers of violent and threatening
      incidents.

PMID- 16635935
TI  - General health and well-being in outpatients with depressive and bipolar
      disorders.
AB  - Prior studies have found contradictory results regarding the association between
      course of illness and quality of life among patients with depressive disorder or
      bipolar disorder. Questionnaires about quality of life and affective symptoms
      (the EQ-5D, EQ-5D-VAS, WHO (Five) well-being index and the BDI-42) were mailed to
      a large population of outpatients with depressive or bipolar disorder
      representative of patients treated in hospital settings in Denmark. Among the
      1005 recipients, 49.9% responded to the letter. Depressive disorder was
      associated with poorer general health (EQ-5D, EQ-5D-VAS) and well-being (WHO
      (Five) well-being index) and more depressive and anxiety symptoms compared with
      bipolar disorder. Similarly, more psychiatric admissions were associated with
      poorer general health and well-being and more depressive and anxiety symptoms.
      However, when adjusting for the effect of depressive symptoms, the associations
      between number of admissions and general health, and between numbers of
      admissions and well-being, lost significance. Thus, depressive symptoms seem to
      be the strongest predictor of general health and well-being in both disorders. As
      the response rate to the questionnaire was relatively low, the findings should be
      interpreted with caution.

PMID- 16635936
TI  - Drug addiction in hepatitis C patients leads to a lower quality of life.
AB  - The subjective health status of hepatitis C patients has been relatively poorly
      studied. By using the Short Form 36 (SF-36), health-related quality of life
      (HRQOL) was assessed in a group of 42 hepatitis C patients. In all nine scales
      examined, the scores were generally low, and present drug use and being single
      were associated with especially large reductions in HRQOL. Compared with the
      Norwegian norms, scores were lower across all nine scales and significantly lower
      in eight. The study showed that the hepatitis C patients had definite reductions
      in HRQOL, but the impairment could not be fully explained by their hepatitis.
      Different non-viral factors such as drug use and marital status significantly
      influenced the results. This underlines the importance of taking other factors
      into account when studying the health status of hepatitis C patients.

PMID- 16635937
TI  - Risk factors of future suicide in suicide attempters--a comparison between
      suicides and matched survivors.
AB  - The objective of this study was to find risk factors for suicide by looking for
      clinical and care/treatment consumption differences between 15 hospitalized
      suicide attempters, who later committed suicide ("completers"), and 15 suicide
      attempters who did not ("non-completers"), matched according to sex, age and
      principal diagnosis. Completers had significantly more often attempted suicide
      after the index admission. After index, completers had received more psychiatric
      care and treatment than non-completers. Comorbidity was common in both groups of
      patients. Personality disorders according to the DSM III-R, axis II, Cluster B,
      however, tended to be more common in the completer group. Increased comorbidity
      over time could also be seen to a larger extent in completers. In spite of the
      matching of principal diagnosis, completers tended to have higher Montgomery
      Asberg Depression Rating Scale ratings than non-completers. They also had
      significantly higher Suicide Assessment Scale (SUAS) scores. From this study, it
      is apparent that suicide attempters at risk of future suicide have major and
      multiple psychiatric problems, which cause difficulties in the care and
      treatment.

PMID- 16635938
TI  - Factor structure and individual patterns of DSM-IV conduct disorder criteria in
      adolescent psychiatric inpatients.
AB  - We investigated the factor structure of the DSM-IV conduct disorder (CD)
      diagnostic criteria and typical individual patterns of CD subscales in an
      adolescent inpatient population using detailed hospital records of a Norwegian
      nationwide sample of 1087 adolescent psychiatric inpatients scored for the 15 DSM
      IV CD criteria. Varimax rotated principal components and full-information factor
      analyses of 12 CD criteria were carried out separately for boys and girls
      employing two methods. Standardized values on three subscales of CD criteria were
      subjected to Ward's method of hierarchical cluster analyses followed by k-means
      relocation employing a double cross-replication design. Similar factor structures
      emerged regardless of factoring method and gender. With the exception of Criteria
      8 ("Fire setting") and 14 ("Run away from home") the factor loadings for both
      genders were in accordance with Loeber's tripartite model, with Aggression,
      Delinquency, and Rule Breaking factors largely corresponding to Loeber's overt,
      covert and authority conflict pathways. A five-cluster solution proved highly
      replicable and interpretable. One cluster gathered adolescents without CD, and
      the remaining four described groups with different conceptually meaningful
      constellations of CD criteria, which were not equally prevalent in each gender.
      Delinquency appeared in all symptomatic clusters. The cluster analytic results
      highlighted typical forms of expressions of conduct problems, and the fact that
      these forms may not be equally prevalent in girls and boys even while the
      underlying structure of conduct problems may be similar across genders. Future
      research should address the prediction of specific outcomes from CD criteria
      subscales or constellations.

PMID- 16635939
TI  - Patient satisfaction and treatment environment: a 20-year follow-up study from an
      acute psychiatric ward.
AB  - The aim of this study was to examine to what extent the different subscales of
      the Ward Atmosphere Scale (WAS) are related to patient satisfaction on wards for
      psychotic patients. We wanted to examine if it was possible to replicate previous
      findings from cross-sectional studies and improve the understanding of which of
      the WAS subscales that should be considered the most important for patient
      satisfaction. From 1981 through 2000, the ward atmosphere, in an acute
      psychiatric ward, was evaluated 11 times with the Ward Atmosphere Scale (WAS). A
      total of 129 patients completed the WAS as well as a General Satisfaction Index
      (GSI) comprising three items. Z-scores were calculated to describe the
      fluctuations in the GSI and the WAS subscales. Four of the WAS subscales,
      Involvement, Practical orientation, Angry and aggressive behavior and Staff
      control, strongly co-varied with patient satisfaction. Unexpectedly, the Support
      and Order and organization subscales correlated only moderately with patient
      satisfaction. The remaining five WAS subscales (Spontaneous behavior, Autonomy,
      Personal problem orientation, Program clarity and Staff attitude to expressed
      feelings) were only weakly correlated with patient satisfaction. This study
      confirms that four of the six assumedly most important WAS subscales are strongly
      related to patient satisfaction on wards for psychotic patients. Changes in these
      WAS subscales seems to be paralleled by changes in patient satisfaction in the
      expected direction.

PMID- 16635940
TI  - Olanzapine plasma level in relation to antimanic effect in the acute therapy of
      manic states.
AB  - The aim of this study was to evaluate internal as well as external validity of
      the two most frequently used mania scales, the Young Mania Rating Scale (YMRS)
      and the Bech-Rafaelsen Mania Scale (MAS), in patients with DSM-IV mania. Mokken
      analysis was used to evaluate internal validity in which a coefficient of
      homogeneity of 0.40 or higher indicates that the total score is a sufficient
      statistic. The external validity was evaluated by plasma-level relationship of
      olanzapine. In total, 20 patients with DSM-IV mania were analysed, and the
      coefficient of homogeneity was acceptable for the MAS, but not for the YMRS. In a
      subgroup of females who over 2 weeks had received a fixed dose of 20 mg
      olanzapine daily, a significant association was found between MAS scores and
      plasma levels, but this association was not obtained with the YMRS. In
      conclusion, the MAS was found superior to the YMRS in regard to both internal and
      external validity.

PMID- 16635941
TI  - The prevalence of chronic fatigue syndrome in Iceland--a national comparison by
      gender drawing on four different criteria.

PMID- 16635942
TI  - TANF policy: past, present, and future directions.
AB  - The purpose of this article is to offer a brief and concise history of relevant
      public welfare policies for a discussion of the effects of public welfare reform,
      and how it impacts families in ways not comprehensively understood. Social
      scientists' concerns about the potential for the families to be thrust into an
      "extreme poverty" status due to the forced workforce participation requirement
      and expiration of time limited benefits is discussed. A second concern regarding
      a "one size fits all" approach to work requirements for TANF recipients being
      unrealistic and insensitive is also discussed. The authors recommend a
      comprehensive multi-system analysis to determine the impact of welfare reform.
      There is also a recommendation that the workforce requirements should correlate
      to an assessment score based on the ability of welfare recipients to function in
      identified areas. Implications of maintaining a welfare reform policy status quo
      are identified.

PMID- 16635943
TI  - The rights of the medically uninsured: an analysis of social justice and
      disparate health outcomes.
AB  - As technological advances in the United States continue to improve the
      effectiveness of medical interventions, expectations among Americans of both
      improved health and extended life expectancy have also increased. At the same
      time, many of the population continue to lack the insurance necessary to access
      even the most basic healthcare services (Institute of Medicine, 2004; Tunzi,
      2004; Saha & Bindman, 2001). With approximately 18,000 avoidable deaths
      attributed annually to inadequate medical coverage and 43.6 million individuals
      currently without insurance benefits, the need to address the disparity in access
      to treatment and a means of social justice in the distribution of health care is
      all too clear (Crispen & Whalen, 2004). As a nation relying on market mechanisms
      to regulate the costs and quality of available health resources (Baldor, 2003;
      Saha&Bindman, 2001), the welfare of society as a whole may soon be threatened by
      the provision of marginal services to a select minority as increasing numbers of
      the uninsured continue to experience less favorable clinical outcomes and higher
      mortality rates (Tunzi, 2004; Litaker & Cebul, 2003; Jackson, 2001; Sox, Burstin,
      Edwards, O'Neil et al., 1998). The author will first examine the consequences of
      being among the growing number of uninsured individuals in the United States.
      Attention will then be given to exploring the social justice issues inherent in
      this critical problem and evaluating these issues through the perspective of both
      libertarian and feminist theory. Using these theories, innovative strategies for
      attaining distributive justice in the provision of health care will be offered
      with recommendations for utilizing these alternative approaches to develop and
      implement future health policy.

PMID- 16635944
TI  - Race and welfare reform: the Wisconsin Works W-2 experience.
AB  - This study examined the impact of welfare reform on African- American and
      Caucasian welfare recipients in Milwaukee, Wisconsin to determine if there were
      differences in their experience with employers and private welfare agencies. The
      study found that despite having higher education levels and higher job training
      completion rates, African-American welfare recipients did not fare any better
      than Caucasians in terms of employment. African-American welfare recipients were
      more likely to be required to take pre-employment tests and Alcohol and Other
      Drug Abuses (AODA) than were Caucasians.

PMID- 16635945
TI  - From the bottom up: tracing the impact of four health-based social movements on
      health and social policies.
AB  - Although health-based social movements organized by grassroots activists have a
      rich history in impacting health and social policy, few systematic studies have
      addressed their policy change efforts or effectiveness. In this article, the
      authors trace how four health-based social movements-the women's health movement,
      ACT UP, breast cancer, and needle exchange-influenced health and social policy
      legislation. The activists' efforts wrested control of "authoritative knowledge"
      that had once been the sole domain of "experts" with advanced medical training.
      They used this knowledge to empower "average" people with medical information,
      promote self help and engage in civil disobedience, which led to changes in
      healthcare delivery, drug testing and approval, and increased research funds for
      HIV/AIDS, breast cancer, and needle exchange. The activists' efforts led to other
      health-based social movements that are currently, or will become, issues for
      health and social policy analysts in the future.

PMID- 16635947
TI  - Changing cultural and social environments: implications for older East Asian
      women.
AB  - The world is aging and the trend is towards a global feminization of aging. In
      the Asia Pacific region, which already contains approximately 50% of the world's
      population over age 60, the number of older women exceeds that of older men in
      most countries. This article explores the changes that are occurring in East
      Asian social and cultural traditions for aging and discusses the implications of
      those changes for women who aged in that culture. In the traditional culture,
      Chinese, Japanese, and Korean families are influenced by values of family
      centrality and collective orientation to life that are mostly rooted in Confucian
      values and ethics. In those traditions, older women assume and maintain a valued
      status within the family and community through respected roles and productive
      contributions. However, various factors, such as migration to urban areas and
      demographic shifts, have precipitated modernization of these societies and
      alterations of traditional culture. These cultural shifts are relevant to the
      United States where, according to the 2000 U.S. Census, 71.0% of Asian and
      Pacific Islander-Americans over the age 65 are foreign-born. Immigration can
      prompt an immediate cultural shift and create a fast forward insight into the
      slower cultural evolution currently occurring in East Asian societies.

PMID- 16635948
TI  - Healthy postmenopausal women- physical activity and forearm bone mineral density:
      the Nord-Trondelag health survey.
AB  - The aim of this study was to analyze the association between Physical Activity
      (PA) and forearm bone mineral density (BMD) in healthy postmenopausal women.
      During 1984-1986, a population-based health survey (HUNT-1) was conducted in Nord
      Trondelag county, Norway. The second follow-up survey (HUNT-2) was conducted
      during 1995-1997. The subjects consist of all healthy postmenopausal women (N =
      2,924). Higher intensity of recreational PA in HUNT-1 was associated with higher
      BMD ultradistally (slope = +0.0084, p = 0.0009). The summary score of duration,
      frequency and intensity of recreational PA in HUNT-1 was associated with lower
      risk of being below the 20th percentile ultradistally (OR = 0.90, p = 0.01, after
      adjustment for covariates). The trends for mean distal and ultradistal BMD and
      percent low BMD lacked statistical significance when we used the PA score that
      combined the recreational and occupational PA in HUNT-1 and HUNT-2. CONCLUSION:
      Higher intensity of prior recreational PA (HUNT-1) was associated with a
      protective effect on BMD measured in the forearm (HUNT- 2).

PMID- 16635949
TI  - Societal influences on body image dissatisfaction in younger and older women.
AB  - Few studies have examined older women's body image. This study compared body
      image dissatisfaction (BID) and weight control practices; evaluated associations
      among BID, societal influences and concern for appropriateness (CFA); and
      identified the most important correlate of BID among younger (19-23) and older
      women (65-74). Questionnaires obtained information on demographics, weight
      control practices, societal influences (SATAQ-3), CFA and BID using the Figure
      Rating Scale. Findings revealed no difference in the prevalence of BID. The
      number of weight control practices and SATAQ-3 and CFA scores were correlated to
      BID. Pressure from the media was the most significant correlate of BID.

PMID- 16635950
TI  - Impact of senior center friendships on aging women who live alone.
AB  - Elderly women who live alone are considered at greater risk for loneliness,
      depression, and decreased mobility. This paper examines the influences of late
      life friendships and senior center activities on the health and well-being of
      aging women living alone. Based on the findings from 274 women living alone it
      was found that the senior center is an excellent environment where new supportive
      friendships can easily be formed. These friendships and other center activities
      have positive mental and physical outcomes. Using a comparison group of 171
      elderly women living with their spouses, it was discovered that women who lived
      alone participated in center activities more frequently and, as a result, also
      created a social network that extended outside of the center environment.

PMID- 16635951
TI  - Older Women's Health and Its Impact on Wealth.
AB  - As many elderly women tend to outlive their spouses, there is a growing
      population of unmarried elderly women. Unmarried women are worse off than married
      women both financially and physically. A question that has not been answered is
      whether and how the relationship between health and wealth differs across elderly
      women's marital status. Do the negative impacts of health problems cause more
      serious financial consequences for unmarried elderly women than married women?
      Using the five waves of data from the Asset and Health Dynamics Among the Oldest
      Old (AHEAD) from 1993 to 2002, this question is empirically investigated. Results
      indicate that severe chronic conditions result in 4 to 10% greater wealth
      depletion for unmarried women than married women. This finding calls for
      heightened awareness of the negative financial consequences of health problems
      and also calls for increased lifetime earning potential, reconsideration of
      women's retirement benefits, and greater attention to preventive care.

PMID- 16635953
TI  - HSCL LibQUAL+ 2004: from numbers and graphs to practical application.
AB  - The University of Florida Health Science Center Libraries created a task force
      representing various departments to review data from its 2004 LibQUAL+ survey.
      This review compared results from the 2002 and 2004 LibQUAL+ surveys, and the
      data from the Association of Academic Health Science Libraries 2004 cohort. The
      task force analyzed the key components of the LibQUAL+ survey: Affect of Service,
      Information Control, Library as Place, and user comments. At the conclusion of
      this review, the task force made recommendations and suggestions along
      departmental lines to meet the patrons' needs and expectations. In addition to
      following the task force recommendations, the Libraries independently implemented
      several new services and hired additional personnel after the completion of the
      2004 survey. Combined, these changes should improve overall library service and
      increase customer satisfaction. Looking towards the 2006 LibQUAL+ survey, the
      task force will be convened in advance and will guide the entire process.

PMID- 16635954
TI  - Developing and sustaining a web-based library newsletter.
AB  - The JEFFLINE Forum, Scott Library's attempt to revive the traditional library
      newsletter by employing the technical advantages and increasing presence of the
      Web, debuted in October 1999. The fifth anniversary of the Forum was a good time
      to look back at its evolution and to examine some of the challenges inherent in
      developing and sustaining a library newsletter. By identifying the most
      successful strategies, and reflecting on the lessons learned along way, the
      authors hope to continue the evolution of the Forum and help to ensure the
      viability of the library newsletter.

PMID- 16635955
TI  - Making sense of disorders of hemostasis and thrombosis at the reference desk.
AB  - This paper discusses concepts and terminology of some aspects of disorders of
      hemostasis (stopping bleeding) and thrombosis (blood clotting) as it relates to
      medical reference work. Details of anatomic, biochemical, and pathologic
      processes are not discussed. Specific terminology involved in this area will be
      reviewed in order to help ensure a good approach to developing prudent strategies
      for database searching of the medical literature. MeSH thesauri terms are
      discussed and text word synonyms are presented that provide tools for thorough
      searching techniques. Examples of specific search strategies are illustrated.

PMID- 16635956
TI  - An introductory guide to drug reference sources.
AB  - A huge number of drug reference sources exist. For the librarian new to the drug
      information field, choosing the appropriate source to answer a reference question
      can be difficult. This paper presents some common drug reference questions and
      some of the American, British, and Canadian tools best suited to answering them.

PMID- 16635957
TI  - The Literature, Arts, and Medicine Database from the New York University School
      of Medicine.
AB  - The Literature, Arts, and Medicine Database is a unique database created and
      maintained by the New York University School of Medicine, freely available to all
      on the Web. Focusing on the medical humanities, it provides annotations to over
      2,000 works of art such as paintings, poetry, prose, plays, and film. The
      annotations are written by an eclectic group of scholars that includes
      physicians, scientists, poets, historians, and critics.

PMID- 16635958
TI  - Current awareness in the new millennium: RSS.
AB  - Keeping current is essential for both patrons and librarians in the health
      sciences. We receive electronic and photocopied tables of contents. We subscribe
      to relevant mailing lists, newspapers and magazines. We review Web sites, books
      and journals. Our desks are littered with current awareness items that more often
      get old than read. RSS or "Really Simple Syndication' is a means of organizing
      and simplifying current awareness efforts. Using RSS feeds from a variety of
      sources along with aggregator software, librarians can keep up-to-date without
      the clutter. This article will provide a starting point from which to take
      advantage of RSS and continue the process of active learning.

PMID- 16635959
TI  - Librarians in the Woods Hole Biomedical Informatics course.
AB  - What has come to be known as the "Woods Hole course", Biomedical Informatics, is
      a week-long course sponsored by the National Library of Medicine which has been
      offered since 1992. Its participants include librarians, clinicians, educators,
      and administrators. This article discusses the content of the course and its
      applicability to medical librarians.

PMID- 16635960
TI  - Web tutorials: bibliographic instruction in a new medium.
AB  - Libraries are adding electronic resources of all kinds at an increasing pace to
      provide service to users outside the library and around the world. To meet this
      new demand, libraries are turning more and more to the use of online tutorials as
      a valuable means of providing instruction on how to access and use important
      resources. This article describes the Health Sciences Library and
      Biocommunications Center's work and experiences while creating tutorials, the
      ideas used, and ways the work was evaluated.

PMID- 16635963
TI  - Urtica dioica for treatment of benign prostatic hyperplasia: a prospective,
      randomized, double-blind, placebo-controlled, crossover study.
AB  - PURPOSE: To determine the effects of therapy with Urtica dioica for symptomatic
      relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH). MATERIAL AND METHODS: A 6-month, double-blind, placebo
      controlled, randomized, partial crossover, comparative trial of Urtica dioica
      with placebo in 620 patients was conducted. Patients were evaluated using the
      International Prostate Symptom Score (IPSS), the maximum urinary flow rate
      (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen
      (PSA), testosterone levels, and prostate size. At the end of 6-month trial,
      unblinding revealed that patients who initially received the placebo were
      switched to Urtica dioica. Both groups continued the medication up to 18 months.
      RESULTS: 558 patients (90%) completed the study (287/305, 91% in the Urtica
      dioica group, and 271/315, 86% in the placebo group). By intention- to-treat
      analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica
      dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the
      placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with
      drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica
      and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4
      mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In
      Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P <
      0.05). No appreciable change was seen in the placebo group. Serum PSA and
      testosterone levels were unchanged in both groups. A modest decrease in prostate
      size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica
      group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the
      prostate volume at the end of study with placebo. At 18-month follow-up, only
      patients who continued therapy, had a favorable treatment variables value. No
      side effects were identified in either group. CONCLUSION: In the present study,
      Urtica dioica have beneficial effects in the treatment of symptomatic BPH.
      Further clinical trials should be conducted to confirm these results before
      concluding that Urtica dioica is effective.

PMID- 16635964
TI  - Anti-anxiety activity studies of various extracts of Turnera aphrodisiaca Ward.
AB  - Turnera aphrodisiaca Ward (Turneraceae) has been used traditionally for treatment
      of anxiety neurosis and as an aphrodisiac. Yet, the plant has never been
      subjected to systematic biological investigation. In the present investigation,
      petroleum ether (60-80 degrees C), chloroform, methanol, and water extracts of T.
      aphrodisiaca aerial parts were evaluated for anti-anxiety activity in mice using
      elevated plus-maze apparatus. Among all the extracts, only methanol exhibited
      significant anti-anxiety activity at a dose of 25 mg/kg with respect to control
      as well as standard (diazepam, 2 mg/kg). The bioactive methanol extract was
      shaken with petroleum ether, chloroform, and n-butyl alcohol, and all the
      shakings as well as the remaining methanol extract (RME) were further evaluated
      for anxiolytic activity. Butanol fraction and RME were found to exhibit
      anxiolytic activity in mice at the dose of 10 mg/kg and 75 mg/kg, respectively.

PMID- 16635965
TI  - Some compaction characteristics of the hot water leaf extract og Nauclea
      latifiola: a potential antimalarial agent.
AB  - This study aims to develop a suitable tablet dosage form of Nauclea latifolia, a
      potential antimalarial agent. The compaction characteristics of the oven dried
      water extract were studied using the Heckel equation. The mechanical properties
      of the compacts were also determined. This preliminary information will be useful
      in developing a suitable dosage form of the extract for use in the management of
      malaria. The results showed that N. latifolia extract exhibited high
      densification due to dye filling while the subsequent rearrangement of the
      granules did not contribute, significantly, to their densification. The granules
      had enhanced plasticity as shown by the low yield point, Py. The tablets produced
      from the extract had good mechanical properties, with hardness increasing via
      compression pressure while the friability decreased. However, the tablets had
      poor disintegration properties; it is concluded that while tablets of suitable
      physical properties can be produced from the extract, a disintegrant would need
      to be included in the formulation to ensure adequate drug release.

PMID- 16635966
TI  - Detection and determination of chemical groups in an extract of Allophylus
      cominia (L.).
AB  - The preliminary chemical characterization of the aqueous extract of Allophylus
      cominia (L.) Sw leaves was carried out by a phytochemical screening, the
      determination of the protein concentration by Lowry's method, as well as the
      composition of fatty acids and carbohydrates by gaseous chromatography (GC). The
      presence of the free amine groups, free phenolics, tannins, leucoantocianidines,
      saponines, triterpens, and steroids was detected. The concentration of proteins
      were 6.22 mg/mL. The composition of fatty acids (%) were: lauric acid (C12):
      1.87; miristic acid (C14): 9.13; palmitic acid (C16): 19.87; stearic acid (C18):
      8.35; and araquidic acid (C20): 7.83. The identified carbohydrates (mg/mg totals)
      were: arabinose: 0.06; xilose: 0.025; galactose: 0.241; and glucose: 1.2. Some
      members of these analyzed groups are reported in literature as potent
      hypoglycemic agents. For this reason, the presence of these substances in the
      analyzed extract may be one of the factors that contribute to the pharmacological
      effect of their administration in experimental diabetic models.

PMID- 16635967
TI  - Protective effects of ethanolic neem leaf extract on DMBA-induced genotoxicity
      and oxidative stress in mice.
AB  - We evaluated the effects of pretreatment with ethanolic neem leaf extract on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced genotoxicity and oxidative stress in
      male Swiss albino mice. The frequency of bone marrow micronuclei, the extent of
      hepatic lipid peroxidation and the status of antioxidants-reduced glutathione
      (GSH), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were used
      as intermediate biomarkers of chemoprotection. In DMBA-treated mice, the
      increases in micronuclei and lipid peroxides were accompanied by compromised
      antioxidant defenses. Pretreatment with ethanolic neem leaf extract (200 mg/kg
      body weight) significantly reduced DMBA-induced micronuclei and lipid peroxides
      and enhanced GSH-dependent antioxidant activities. The results of the present
      study suggest that ethanolic neem leaf extract exerts protective effects against
      DMBA-induced genotoxicity and oxidative stress by enhancing the antioxidant
      status.

PMID- 16635968
TI  - Cardioprotective activity of A.V. Circulo in isoproterenol-induced myocardial
      necrosis.
AB  - Cardioprotective activity of A.V. Circulo, a polyherbal preparation, was
      evaluated in isoproterenol induced myocardial damage in rats. Chronic
      prophylactic treatment with A.V. Circulo prevented an increase in serum lysosomal
      enzyme activity of creatinine phosphokinase, lactate dehydrogenase, and serum
      glutamate oxaloacetic transaminase in the blood due to isoproterenol
      administration. A.V. Circulo treatment also significantly inhibited increases in
      DNA and protein content in heart tissue as well as elevated serum lipid levels
      after isoproterenol administration. Treatment was also able to inhibit the
      isoproterenol induced increase in heart weight to body weight ratio. Pretreatment
      with the polyherbal restored the altered architectural changes in the histology
      of myocardium, due to isoproterenol administration. All findings, including
      biological, biochemical, and histopathological indicate that A.V. Circulo
      treatment chronically protected the cardiac injury.

PMID- 16635969
TI  - July, 2005 edited excerpts from: complex herbs-complete medicines, Eclectic
      Medical Publications, Sandy, OR, 2004.

PMID- 16635970
TI  - Lemon balm (Melissa officinalis L.): an evidence-based systematic review by the
      Natural Standard Research Collaboration.
AB  - An evidence-based systematic review including written and statistical analysis of
      scientific analysis of scientific literature, expert opinion, folkloric
      precedent, history, pharmacology, kinetic/dynamics, interactions, adverse effect,
      toxicology, and dosing.

PMID- 16635971
TI  - Understanding and responding to racial differences in drug court outcomes.
AB  - Significant differences in outcomes and characteristics exist between Caucasians
      and African-Americans in ten Missouri adult drug courts. Caucasians are more
      likely to graduate and they differ in significant ways from African-Americans in
      the context in which they lived their lives prior to drug court. Differences were
      significant between the two groups in employment levels at entry, primary drug of
      choice, levels of positive family support, and socioeconomic status. Using the
      evidence from this study, ways that treatment providers can better meet the needs
      of African-Americans are discussed.

PMID- 16635972
TI  - Health services usage by Alaskan injection drug users.
AB  - OBJECTIVES: The purpose of this study was to explore health services usage among
      injection drug users in Anchorage, Alaska. DESIGN: 645 participants were
      recruited as part of a federally funded study of needle exchanges. They completed
      a health services usage questionnaire that elicited information on use of a
      health care provider (physician or nurse) and emergency room services. Chi-square
      and t-tests were used for the bivariate analyses, and multiple logistic
      regression was used to develop the final predictive models. RESULTS: The majority
      of respondents (n = 646) were male (77 percent). Race/ethnicity included 58
      percent White, 22 percent Alaska Native, and 20 percent African American. The
      multivariate model predicting accessing a health care provider (HCP) included
      ever having had chlamydia (OR 2.7, CI 1.6, 4.5), current income from welfare or
      public assistance (OR 2.6, CI 1.7, 3.9), current income from disability (OR 5.0,
      CI 2.2, 11.4), current income from SSI (OR .30, CI .12, .77) and the number of
      days in the last 30 used opiates other than heroin (OR 1.04, CI 1.002, 1.078).
      The multivariate model predicting use of an emergency room (ER) was similar to
      that predicting use of an HCP, with the additional finding of a negative
      association between being African American and ER use. CONCLUSION: The role of
      public assistance benefits enabling access to health care for IDUs has policy
      implications. Large public programs, such as the Indian Health Service, paid for
      much of the health care received by the IDUs recruited as part of this study.

PMID- 16635973
TI  - Racial and ethnic differences in health and health care: lessons from an inner
      city patient population actively using heroin and cocaine.
AB  - This study describes differences in health care utilization and recorded
      diagnoses in a racially and ethnically diverse sample of 1175 out-of-treatment
      patients who screened positive for heroin and cocaine use during an outpatient
      visit to a drop-in clinic at an urban hospital. Blacks averaged more ED visits
      than Whites and higher average yearly ED charges than Hispanics (1,991 dollars
      vs. 1,603 dollars). Charges over two years totaled 6,111,660 dollars. Blacks were
      most likely to be diagnosed with injury, hypertension, cardiac disease, alcohol
      abuse/dependency, and sexually transmitted disease, and least likely to be
      diagnosed with psychiatric disease. Hispanics were most likely to be diagnosed
      with HIV, dental disease and drug overdoses, and least likely to be injured. Only
      34% of this group of drug users was identified with a diagnosis of drug abuse or
      dependency.

PMID- 16635974
TI  - Understanding differences in marijuana use among urban Black and suburban White
      high school students from two U.S. community samples.
AB  - To examine community/racial differences in adolescent marijuana use and the
      variations in factors underlying the observed differences, a questionnaire survey
      study was conducted with 9th to 12th graders (n = 1,936) from two communities in
      New Jersey. Marijuana use was significantly higher among suburban (mostly White)
      students than among their urban (mostly Black) counterparts. Significant
      differences in marijuana use between the two community sub-samples were explained
      by differences in type of risk factors, mean number of risk factors, and the
      strength of the association (slopes) between risk factors and marijuana use.
      Social-environmental factors (including positive after-school activities and
      negative peer influences) and, to a lesser degree, family factors (including
      family income, parental and sibling drug use), accounted for most
      community/racial differences in marijuana use.

PMID- 16635975
TI  - Effects of acculturation and social norms on adolescent smoking among Asian
      American subgroups.
AB  - This study provides new information about how acculturation and perceived social
      norms affect adolescents smoking among four Asian-American subgroups. Results
      showed differences in smoking prevalence rates across subgroups, with Koreans
      having the highest rates of smoking, while Chinese have the lowest rates. In
      contrast to the large gender disparity in the ancestral countries, smoking rates
      were equal for Asian-American boys and girls. Acculturation was significantly
      associated with an increased risk for lifetime smoking for Asian-American girls,
      but not for boys. Perceived social norms regarding peer smoking were
      significantly associated with smoking behaviors for both genders and for all
      subgroups.

PMID- 16635976
TI  - Religious and spiritual elements of change in Sikh men with alcohol problems: a
      qualitative exploration.
AB  - The research presented aimed to explore and elucidate religious and spiritual
      elements involved in the change process for South Asian men overcoming alcohol
      problems. In-depth interviews with 15 Sikh men who had either accessed
      counselling services, and/or used religious/spiritual strategies to overcome an
      alcohol problem were carried out. A grounded theory approach was used to analyse
      the data. Change was seen to occur within a holistic framework, impacting on many
      levels of the person and their context. A model of behaviour change was developed
      identifying 3 phases of change labelled as catalyst, commitment, and maintenance
      within which specific religious and spiritual change processes took place. The
      findings have important implications for the provision of culturally appropriate
      alcohol treatment services.

PMID- 16635977
TI  - Language, income, education, and alcohol-related fatal motor vehicle crashes.
AB  - This paper investigates the role of race/ethnicity, language skills (a proxy for
      acculturation among Hispanics in Arizona, California, New Mexico, and Texas),
      income, and education level on alcohol-related fatal motor vehicle crashes. Using
      the Fatality Analysis Reporting System (FARS), we confirmed previous state-based
      studies showing that high income and education levels have a protective influence
      on alcohol-related fatal motor vehicle crashes. We also confirmed that language
      proficiency/acculturation tends to increase the vulnerability of Hispanic women
      to alcohol-related fatalities. Differences in alcohol-related fatality rates
      across Hispanic subgroups are observed. Future reductions in alcohol-related
      traffic fatalities may require prevention policies that take into account
      existent variations in acculturation, income, and education among racial/ethnic
      groups and subgroups.

PMID- 16635978
TI  - Strengthening home and community-based care through Medicaid waivers.
AB  - States are increasingly using the Medicaid 1915c waiver program to provide
      community-based long-term care (LTC). We examined state predictors of waiver
      utilization and expenditures for waivers serving both older and working-age
      individuals. State level data for the period 1992 to 2001 were used to estimate
      random effects panel models. States with increased community-based care (e.g.,
      home health agencies) and decreased nursing home bed capacity were positively
      associated with state per capita rates of use, expenditures, and the share of
      Medicaid LTC dollars supporting 1915c waivers. States appeared to substitute
      Medicare for Medicaid services for individuals eligible for both. State per
      capita income was positively related to each measure. State policies that
      facilitate decreased institutional and increased community- based capacity appear
      essential to state efforts to expand access to community-based services. Federal
      policies that address state resource issues may also spur growth in community
      based LTC, which, in most states, continues to be limited.

PMID- 16635979
TI  - Nursing home performance on select publicly reported quality indicators and
      resident risk of hospitalization: grappling with policy implications.
AB  - This study examines how resident risk of hospitalization varies in relation to
      facility performance on select quality indicators (QIs). Using a 15% sample,
      three years of Medicaid reimbursement data from over 525 nursing homes (NHs) were
      linked with four years of hospital claims data and facility-level data to
      investigate whether residents of NHs with worse (better) than expected
      performance on QIs experienced increased (decreased) risk of hospitalization.
      Logistic regression results indicate that variations in hospitalization risk
      among NH residents are explained in part by facility performance on QIs.
      Residents from NHs with more decubitus ulcers, with greater use of physical
      restraints, and with a higher than expected incidence of unexplained weight
      loss/gain experienced increased risk of hospitalization.

PMID- 16635980
TI  - Implications of welfare reform on the elderly: a case study of provider,
      advocate, and consumer perspectives.
AB  - Whereas many studies of welfare reform have focused on effects on children and
      families, little research has examined the implications of welfare reform for the
      elderly. This case study incorporates interviews with service providers for the
      aging, members of advocacy organizations, and two focus groups of older consumers
      conducted in the multi-ethnic urban community of San Francisco. Study findings
      suggest that welfare reform has had both direct and indirect effects on the
      elderly and their services in the study community. Direct effects derive
      primarily from changes in the welfare reform legislation that had the effect of
      undermining both immigrants' eligibility for and claiming of public assistance
      benefits. Indirect effects on older persons include increased child-care demands
      upon grandparents. The case study data bear on a significant policy change within
      the broader trend of devolution at a historical point when anti-immigrant
      sentiment in the United States was running high.

PMID- 16635981
TI  - Bringing assisted living services into congregate housing: housing directors'
      perspectives.
AB  - The purpose of this research is to explore the impact of an Assisted Living
      Services (ALS) program on directors of state-funded congregate housing. Using
      focus groups, we interviewed congregate housing directors about how adding the
      ALS program to their facilities impacted their management experiences. Four
      themes emerged from the analysis of the focus group data: (1) importance of
      assisted living services for promoting aging in place; (2) "costs" of offering
      ALS; (3) differences in how the ALS program was implemented; and (4)
      organizational issues emerging from the merger of housing and health-care models.
      Based on the present findings, we propose a number of policy issues that need to
      be addressed when services are added to existing housing.

PMID- 16635982
TI  - Client satisfaction with home care services in rural Russia.
AB  - The objective of this work is to explore the satisfaction of a sample of 300
      frail elders living in a rural Russian area with the support services provided by
      social service agency staff. The client population lives in extremely difficult
      conditions in terms of housing and associated communal services. They reported
      very high levels of satisfaction with the agency-provided services, both general
      satisfaction and their satisfaction with the specific services received during
      the reference visit inquired about by the interviewer. The degree of satisfaction
      is likely related to the difficulty of their living environment and their
      probable poverty, as well as the quality of services received. Attempts to relate
      the variance in the satisfaction ratings to the extent of activity limitations
      and the volume of formal and informal care using multivariate analysis met with
      limited success, owing in part, at least, to the limited variance in the
      dependent variables. Nevertheless, the patterns identified are broadly consistent
      with expectations based on modeling previously done for the U.S. populations
      receiving at-home care. The results clearly indicate the value of providing such
      services to frail elders in such circumstances.

PMID- 16635983
TI  - A quantitative analysis of Arabidopsis plasma membrane using trypsin-catalyzed
      (18)O labeling.
AB  - Typical mass spectrometry-based protein lists from purified fractions are
      confounded by the absence of tools for evaluating contaminants. In this report,
      we compare the results of a standard survey experiment using an ion trap mass
      spectrometer with those obtained using dual isotope labeling and a Q-TOF mass
      spectrometer to quantify the degree of enrichment of proteins in purified
      subcellular fractions of Arabidopsis plasma membrane. Incorporation of a stable
      isotope, either H(2)(18)O or H(2)(16)O, during trypsinization allowed relative
      quantification of the degree of enrichment of proteins within membranes after
      phase partitioning with polyethylene glycol/dextran mixtures. The ratios allowed
      the quantification of 174 membrane-associated proteins with 70 showing plasma
      membrane enrichment equal to or greater than ATP-dependent proton pumps,
      canonical plasma membrane proteins. Enriched proteins included several hallmark
      plasma membrane proteins, such as H(+)-ATPases, aquaporins, receptor-like
      kinases, and various transporters, as well as a number of proteins with unknown
      functions. Most importantly, a comparison of the datasets from a sequencing
      "survey" analysis using the ion trap mass spectrometer with that from the
      quantitative dual isotope labeling ratio method indicates that as many as one
      fourth of the putative survey identifications are biological contaminants rather
      than bona fide plasma membrane proteins.

PMID- 16635984
TI  - A high efficiency strategy for binding property characterization of peptide
      binding domains.
AB  - A large proportion of protein-protein interactions is mediated by families of
      peptide-binding domains. Comprehensive characterization of each of these domains
      is critical for understanding the mechanisms and networks of protein interaction
      at the domain level. However, existing methods are all based on large scale
      screenings for each domain that are inefficient to deal with hundreds of members
      in major domain families. We developed a systematic strategy for efficient
      binding property characterization of peptide-binding domains based on high
      throughput validation screening of a specialized candidate ligand library using
      yeast two-hybrid mating array. Its outstanding feature is that the overall
      efficiency is dramatically improved compared with that of traditional screening,
      and it will be higher as the system cycles. PDZ domain family was first used to
      test the strategy. Five PDZ domains were rapidly characterized. Broader binding
      properties were identified compared with other methods, including novel
      recognition specificities that provided the basis for major revision of
      conventional PDZ classification. Several novel interactions were discovered,
      serving as significant clues for further functional investigation. This strategy
      can be easily extended to a variety of peptide-binding domains as a powerful tool
      for comprehensive analysis of domain binding property in proteomic scale.

PMID- 16635985
TI  - Optimization and use of peptide mass measurement accuracy in shotgun proteomics.
AB  - Mass spectrometers that provide high mass accuracy such as FT-ICR instruments are
      increasingly used in proteomic studies. Although the importance of accurately
      determined molecular masses for the identification of biomolecules is generally
      accepted, its role in the analysis of shotgun proteomic data has not been
      thoroughly studied. To gain insight into this role, we used a hybrid linear
      quadrupole ion trap/FT-ICR (LTQ FT) mass spectrometer for LC-MS/MS analysis of a
      highly complex peptide mixture derived from a fraction of the yeast proteome. We
      applied three data-dependent MS/MS acquisition methods. The FT-ICR part of the
      hybrid mass spectrometer was either not exploited, used only for survey MS scans,
      or also used for acquiring selected ion monitoring scans to optimize mass
      accuracy. MS/MS data were assigned with the SEQUEST algorithm, and peptide
      identifications were validated by estimating the number of incorrect assignments
      using the composite target/decoy database search strategy. We developed a simple
      mass calibration strategy exploiting polydimethylcyclosiloxane background ions as
      calibrant ions. This strategy allowed us to substantially improve mass accuracy
      without reducing the number of MS/MS spectra acquired in an LC-MS/MS run. The
      benefits of high mass accuracy were greatest for assigning MS/MS spectra with low
      signal-to-noise ratios and for assigning phosphopeptides. Confident peptide
      identification rates from these data sets could be doubled by the use of mass
      accuracy information. It was also shown that improving mass accuracy at a cost to
      the MS/MS acquisition rate substantially lowered the sensitivity of LC-MS/MS
      analyses. The use of FT-ICR selected ion monitoring scans to maximize mass
      accuracy reduced the number of protein identifications by 40%.

PMID- 16635986
TI  - European Heart Rhythm Association Guidance Document on cardiac rhythm management
      product performance.

PMID- 16635987
TI  - Radiofrequency ablation in children and adolescents: results in 154 consecutive
      patients.
AB  - AIMS: The experience of using radiofrequency ablation (RFA) for the treatment of
      arrhythmias in children and adolescents is still limited. This study aimed to
      review the most recent results of RF ablation in children and adolescents in a
      highly experienced centre with access to both conventional techniques and non
      fluoroscopic electroanatomic mapping (CARTO). METHODS AND RESULTS: A total of 154
      consecutive patients younger than 19 years treated with RFA during the period
      2000-04 were included. Numbers (%) or median (quartiles) are reported. Age was 15
      (12-17) years, 70 (45%) were males. Five patients (3%) had congenital heart
      disease. RFA was successful in 147/154 patients (95%). Arrhythmia recurrence
      occurred in 11 patients (7%). Procedure time was 55 (35-90) min and fluoroscopy
      time was 8.8 (4-19) min. Number of RF applications was 4 (2-10) and number of RF
      applications >20 s was 2 (1-7). One patient (0.7%) had complicating high-grade
      atrioventricular block. CARTO was used in 18 RF ablation procedures (11%)
      performed in 15 patients. CONCLUSION: RF ablation can be undertaken in children
      and adolescents with a high success rate, few recurrences and complications, very
      short procedure times, and acceptable fluoroscopy times. Non-fluoroscopic
      electroanatomic mapping is helpful in selected patients.

PMID- 16635988
TI  - Successful treatment of drug refractory ventricular tachycardia by omega-3 fatty
      acid supplementation.
AB  - Effective treatment of recurrent drug-refractory ventricular tachycardia is
      difficult, and conventional pharmacological and interventional approaches are
      often ineffective. We present a novel case report illustrating the potential use
      of omega-3 fatty acid supplementation in such patients.

PMID- 16635989
TI  - Detection of microbubble formation during radiofrequency ablation using
      phonocardiography.
AB  - AIMS: To detect and characterize the acoustic energy generated by microbubble
      (MB) formation in an isolated tissue preparation. MB formation during
      radiofrequency (RF) ablation indicates excessive tissue heating and may precede
      explosive 'pops'. Currently, MB formation can only be detected with
      echocardiography. We hypothesized that MB formation can be detected with high
      sensitivity phonocardiography. METHODS AND RESULTS: In a saline bath, RF lesions
      were created in sections of porcine left ventricle, using a 4 mm tip irrigated
      catheter. MB formation was visualized with an echocardiography probe. In 20
      preparations, RF energy was begun at 25 W and increased by 5 W every 20 s until a
      pop occurred. A high-sensitivity computerized phonocardiography transducer with
      frequency bandwidth of 2 kHz and system noise -90 dB (SonoMedica, Inc., Vienna,
      VA, USA) was coupled to the external glass wall of the bath. In 15 of 20 (75%)
      preparations, a characteristic acoustic signature corresponding to MB formation
      was noted before the pop. These signals were within the 600-2000 Hz range and had
      an intensity range of 10-40 dB. The earliest MB and acoustic signals occurred
      51.3+/-51.5 s before the pop. The acoustic signals continued intermittently up to
      10.3+/-12.9 s before the pop. CONCLUSION: The acoustic energy created by MB
      formation can be detected in an isolated tissue preparation, using a computer
      based phonocardiography system. Characteristic acoustic signatures are present
      before pops and correspond to MB formation. Acoustic monitoring for MB formation
      may allow for the titration of cooled RF ablation without echocardiography.

PMID- 16635990
TI  - Recurrent fascicular ventricular tachycardia in myotonic dystrophy.

PMID- 16635991
TI  - Epicardial ablation of syncopal ventricular tachycardia. Utility of the
      electrocardiogram.
AB  - We describe the case of a young man with syncopal ventricular tachycardia, normal
      left ventricular ejection fraction, normal coronary arteries, and a left
      ventricular aneurysm. The ECG during tachycardia suggested an epicardial origin.
      The arrhythmia was successfully treated using a non-surgical transthoracic
      epicardial approach.

PMID- 16635992
TI  - Supraventricular ectopy and recurrence of atrial fibrillation after electrical
      cardioversion.
AB  - AIMS: Paroxysmal atrial fibrillation (AF) is usually preceded by a premature
      atrial complex (PAC). We hypothesized that patients with a high frequency of
      atrial ectopic activity after restoration of sinus rhythm following direct
      current cardioversion would be more likely to experience recurrence of AF.
      METHODS AND RESULTS: Forty-four patients with documented persistent AF were
      studied. A 24 h Holter recording was performed from the day of external direct
      current cardioversion. Patients were reviewed at 1 week, 1 month, and 6 months.
      After 6 months, 59% of patients had experienced a recurrence of AF. Neither the
      frequency of PACs nor the frequency or duration of supraventricular tachycardia
      (SVT) episodes predicted AF recurrence (P=0.60, 0.30, and 0.42, respectively).
      There was a trend towards maximum rate of SVT predicting recurrence of AF
      (P=0.08). CONCLUSION: Frequency of supraventricular ectopy or the number and
      length of SVT runs in the 24 h after restoration of sinus rhythm are not strong
      predictors of recurrence of AF after electrical cardioversion. A larger study
      would be required to detect a small predictive effect.

PMID- 16635993
TI  - Increased AAI mode pacing threshold after termination of atrial fibrillation by
      acute administration of disopyramide phosphate.
AB  - AIMS: We studied changes in atrial pacing threshold after termination of atrial
      fibrillation (AF) by acute administration of disopyramide phosphate (DP) to
      elucidate the suitable setting for atrial pacing output before AF termination.
      METHODS AND RESULTS: Four patients with sick sinus syndrome implanted with AAI
      mode pacemakers were examined. Disopyramide phosphate (2 mg/kg body weight) was
      injected intravenously for termination of a total of eight AF episodes. The
      maximal pacing threshold after AF termination (5.2+/-0.8 V at 0.45 ms) was
      significantly higher than that at baseline (1.3+/-0.2 V at 0.45 ms; P<0.01) and
      the average increment was 433+/-68%. During a period free from AF, an acute
      administration of DP did not increase the atrial pacing threshold and serum
      disopyramide levels were not toxic. CONCLUSION: The increased atrial pacing
      threshold observed after AF termination cannot be explained by the action of DP
      alone. However, our results suggest that atrial pacing output should be set at
      the maximum value before DP is administered to induce AF termination in patients
      with AAI pacemaker-dependent bradyarrhythmias.

PMID- 16635994
TI  - Parasympathetic-mediated atrial fibrillation during tilt test associated with
      increased baroreflex sensitivity.
AB  - The autonomic mechanism that triggered atrial fibrillation in a patient during
      tilt test was investigated. Neurocardiogenic syncope is often characterized by
      diminished baroreflex sensitivity during the hypotension period. Increased
      barorereflex sensitivity preceding the onset of atrial fibrillation in tilt
      testing may indicate the involvement of a vagally mediated mechanism, as shown in
      the present case.

PMID- 16635995
TI  - Upgrade to biventricular pacing in patients with pacing-induced heart failure:
      can resynchronization do the trick?
AB  - Dyssynchrony imposed on ventricular function by right ventricular (RV) apical
      pacing may lead in some cases to worsening or appearance of heart failure (HF)
      symptoms. This is a result of an altered pattern of activation, leading to
      several histological and functional adjustments of the left ventricle, including
      inhomogeneous thickening of the ventricular myocardium and myofibrillar disarray,
      fibrosis, disturbances in ion-handling protein expression, myocardial perfusion
      defects, alterations in sympathetic tone and mitral regurgitation. Studies of mid
      and long-term effects of RV apical pacing on left ventricular (LV) function have
      demonstrated a progressive decline in ejection fraction and other indices of LV
      functional competence. Upgrading RV pacing systems to biventricular
      resynchronization modalities is a theoretically promising option for paced
      patients with worsening HF. The potentially favourable effect of upgrading on LV
      functional indices and patient clinical status has been demonstrated in few, non
      randomized trials. Apart from the scantiness of existing clinical data, issues
      concerning technical aspects of the procedure and selection of eligible patients
      are raised. Is pacing-induced dyssynchrony equivalent to the indigenous
      dyssynchrony in unpaced patients with HF? What selection criteria should be
      applied in order to identify potential responders to cardiac resynchronization
      therapy in this patient population? Answers to these and more questions are still
      lacking.

PMID- 16635996
TI  - Determination of optimal atrioventricular delay for cardiac resynchronization
      therapy using acute non-invasive blood pressure.
AB  - AIMS: In this study, we apply non-invasive blood pressure (BP) monitoring, by
      continuous finger photoplethysmography (Finometer), to detect directly
      haemodynamic responses during adjustment of the atrioventricular (AV) delay of
      cardiac resynchronization therapy (CRT), at different heart rates. METHODS AND
      RESULTS: Twelve patients were studied with six re-attending for reproducibility
      assessment. At each AV delay, systolic BP relative to a reference AV delay of 120
      ms (SBPrel) was calculated. We found that at higher heart rates, altering the AV
      delay had a more pronounced effect on BP (average range of SBPrel=17.4 mmHg)
      compared with resting rates (average range of SBPrel=6.5 mmHg), P<0.0001.
      Secondly, peak AV delay differed between patients (minimum 120 ms, maximum 200
      ms). Thirdly, small changes in AV delay had significant BP effects: programming
      AV delay 40 ms below the peak AV delay reduced SBPrel by 4.9 mmHg (P<0.003);
      having it 40 ms above the peak decreased SBPrel by 4.4 mmHg (P<0.0005). Finally,
      the peak AV delay is highly reproducible both on the same day and at 3 months
      (Bland-Altman difference: 3+/-8 ms). CONCLUSIONS: Continuous non-invasive
      arterial pressure monitoring demonstrates that even small changes in AV delay
      from its haemodynamic peak value have a significant effect on BP. This peak
      varies between individuals, is highly reproducible, and is more pronounced at
      higher heart rates than resting rates.

PMID- 16635997
TI  - Coronary sinus stenting for the stabilization of left ventricular lead during
      resynchronization therapy.
AB  - We report on two patients treated with cardiac resynchronization therapy, in whom
      early (intra-operatively, 64-year-old man) and late (4 months post-operatively,
      57-year-old woman) instability of the left ventricular (LV) lead occurred. In
      order to stabilize the electrodes, stents were deployed in both patients within
      the coronary sinus, into the space between the lead and the wall of the vein
      effectively pinning the lead to the wall. During 3 and 5 months of follow-up, the
      electrodes remained stable and allowed for successful resynchronization in both
      cases. Stenting within the coronary sinus seems to be a safe method for LV lead
      stabilization, which can substantially increase the success rate of
      resynchronization therapy. This new approach, although promising, has to prove
      its safety and should not be practised routinely until long-term follow-up data
      are available.

PMID- 16635998
TI  - Patient Alert to detect ICD lead failure: efficacy, limitations, and implications
      for future algorithms.
AB  - AIMS: An algorithm that alerts implantable cardioverter-defibrillator (ICD)
      patients, in case of abnormal lead impedance (Patient Alerttrade mark,
      Medtronic), may help to recognize lead dysfunction. We aimed to determine the
      utility of Patient Alert for ICD lead-failure detection in a prospective study.
      METHODS AND RESULTS: Three hundred and sixty ICD patients were followed for 22+/
      14 months. Patient Alert was active for pacing impedance <200 and >2000-3000
      Omega, and high-voltage conductor impedance <10-20 and >200 Omega. Ten alert
      events and a total of 29 severe system complications occurred. Patient Alert
      detected three of 10 ICD lead failures, with a positive predictive value (PPV) of
      77.8% for any severe system complication. Retrospective analysis identified 23
      patients with a sensing integrity counter (SIC) >300 and revealed an additional
      four prior undetected lead defects. SIC detected ICD lead failure with 92.9%
      sensitivity and a PPV of 59.1%. Eight of nine patients with a false-positive SIC
      had an integrated bipolar lead. Patient Alert combined with SIC detected all ICD
      lead failures and 71.4% of all severe lead complications. CONCLUSIONS: Patient
      Alert, based on daily lead-impedance measurement, detected one-third of all ICD
      lead failures. Combined use with continuous lead integrity monitoring (SIC)
      increased sensitivity to 100%. Integrated bipolar leads may yield a false
      positive SIC. Incorporating SIC and automated pace/sense threshold measurement
      may improve Patient Alert sensitivity for severe lead complications.

PMID- 16635999
TI  - Do induction cooktops interfere with cardiac pacemakers?
AB  - AIMS: In induction cooktops, coils produce time-varying magnetic fields that
      induce eddy currents in the ferromagnetic bottom of a pot or pan, thereby heating
      it, while the cooktop itself remains cool. Interference with pacemaker sensing
      could conceivably be produced by voltages induced directly by induction or
      indirectly by leakage currents. METHODS AND RESULTS: A worst-case pacemaker
      patient (PP) model representing left-sided implantation of a unipolar pacemaker
      was used for measurement of induced voltages, to judge whether induction cooktops
      could interfere with pacemaker sensing. Eleven induction cooktops of European
      manufacture were tested using the PP model. The pacemaker sensitivity with
      respect to 24 kHz voltages, amplitude-modulated at 100 Hz, was investigated in
      244 devices. The current passing through the body of a grounded patient touching
      a metal pot was determined by measuring the voltage from hand to hand and between
      electrodes placed on the thorax to simulate an implanted unipolar pacing system
      underneath. The results obtained were complex. If the pot is positioned
      concentrically with the induction coil, the smallest pot produced the largest
      stray field, but the induced voltage always remained below the critical value of
      100 mV. With eccentrically positioned large pots, voltages of up to 800 mV could
      be induced. The induced voltage could always be reduced to </=60 mV by
      maintaining a distance of 35 cm. The most sensitive pacemaker reacted at 90.5 mV.
      Because of leakage current, approximately 2% of the voltage between pot and
      ground appears across the pacemaker's sensing input. CONCLUSION: Patients are at
      risk if the implant is unipolar and left-sided, if they stand as close as
      possible to the induction cooktop, and if the pot is not concentric with the
      induction coil. Unipolar pacing systems can sense interference generated by
      leakage currents if the patient touches the pot for a long period of time. The
      most likely response to interference is switching to an asynchronous interference
      mode. Patients with unipolar pacemakers are at risk only if they are not
      pacemaker-dependent.

PMID- 16636000
TI  - Ventricular capture by anodal pacemaker stimulation.
AB  - This report describes the case of an 86-year-old male with syncopal paroxysmal
      2:1 atrioventricular block and a single chamber VVI pacemaker programmed to
      bipolar sensing and unipolar pacing. After recurrence of syncope, a complete loss
      of ventricular capture with regular ventricular sensing was observed on ECG;
      fluoroscopic examination suggested perforation of the right ventricle by the
      helix of the implanted screw-in lead. Reprogramming the pacemaker to bipolar
      pacing/sensing resulted in regular ventricular capture and sensing, suggesting
      effective anodal stimulation from the ring electrode permitting complete non
      invasive palliation.

PMID- 16636001
TI  - Do we need pacemakers resistant to magnetic resonance imaging?

PMID- 16636002
TI  - Potential harmful effects of magnetic resonance imaging in pacemaker patients
      should not be underestimated.

PMID- 16636006
TI  - Pacemakers (PM) and MRI.

PMID- 16636007
TI  - The structures of glycolipids isolated from the highly thermophilic bacterium
      Thermus thermophilus Samu-SA1.
AB  - Thermophiles constitute a class of microorganisms able to grow at extremely
      elevated temperatures. Some of these species are classified as Gram-negative
      bacteria, because of the presence of an outer membrane in the cell envelope,
      which is located on the top of a thick murein layer. Unlike typical Gram-negative
      bacteria, the outer membranes of Thermus species are not composed of
      lipopolysaccharides but of peculiar glycolipids (GL), whose structures seem to be
      strictly involved in the adaptation to high temperatures. In this work, the
      complete structures of the major GL components from the cell envelope of the
      thermophilic bacterium Thermus thermophilus Samu-SA1 are presented. Protocols
      conventionally adopted for Gram-negative bacteria were used, and, for the first
      time, GL from Thermus were analyzed in their native form. Two GL and one
      phosphoglycolipid (PGL) were detected and characterized. The two GL, analyzed by
      nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization Fourier
      transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry, possessed the
      same tetrasaccharide structure linked to a glycerol unit or, alternatively, to a
      long-chain diol. Moreover, a PGL from Thermus was characterized for the first
      time, in which N-glyceroyl-heptadecaneamine was present. These molecules are
      chemically related to other GL from thermophile bacteria, in which they play a
      crucial role in the adaptation of cell membranes to heat.

PMID- 16636008
TI  - Alcohol craving in problem and occasional alcohol drinkers.
AB  - AIMS: The impact of emotional states on alcohol craving has so far mainly been
      investigated in abstinent and actively consuming alcohol addicts. Alcohol craving
      and the variables that influence alcohol craving have not yet been examined in
      non-addicted, alcohol abusing drinkers and non-abusing occasional alcohol
      drinkers. METHODS: In this study 50 problem drinkers and 50 occasional alcohol
      drinkers were investigated. The impact of various craving-related variables such
      as stress and distress, alcohol effect expectancies, and stress coping strategies
      on reward and relief craving was examined and compared between the groups.
      RESULTS: Whereas most occasional drinkers reported little alcohol craving,
      problem drinkers showed a significantly higher amount of reward and relief
      craving accompanied by increased levels of stress-distress and a stronger
      tendency to use negative (inadequate) coping strategies. Stress-distress and
      alcohol effect expectancies were significant predictors of reward and relief
      craving in problem drinkers. In occasional drinkers alcohol craving was not
      related to any of these variables. These variables were also found to be
      predictive of craving in alcohol addicts. CONCLUSIONS: We hypothesized, that in
      non-addicted problem drinkers the expected rewarding and reinforcing alcohol
      effects lead to an early stage of addictive behaviour. Therefore, in this stage
      therapeutic interventions focussing on the awareness of the function of alcohol
      intake as well as alternative coping skills might be useful to prevent alcohol
      dependence in problem drinkers.

PMID- 16636009
TI  - Liver transplantation for alcoholic liver disease: a systematic review of
      psychosocial selection criteria.
AB  - AIMS: To examine the evidence base for psychosocial selection criteria for liver
      transplant candidates with alcoholic liver disease. METHOD: Systematic review
      using three electronic databases supplemented by hand searches. RESULTS: Out of
      96 published studies, 22 were included. All but one were cohort design, most were
      retrospective, single centre, and small sample. Methodology varied considerably,
      such that meta-analysis was not feasible. CONCLUSIONS: Social stability, no close
      relatives with an alcohol problem, older age, no repeated alcohol-treatment
      failures, good compliance with medical care, no current polydrug misuse, and no
      co-existing severe mental disorder have all been associated with future
      abstinence in more studies than not, in those that examined these variables.
      Duration of preoperative abstinence was a poor predictor. We recommend that, if
      predicting future abstinence is considered necessary by transplant teams, a
      standardized approach is agreed and deployed amongst transplant units, then
      audited and reviewed.

PMID- 16636010
TI  - Pregabalin is effective against behavioral and electrographic seizures during
      alcohol withdrawal.
AB  - AIMS: Pregabalin has been shown to possess anticonvulsant, analgesic, and
      anxiolytic properties in a variety of testing situations. This study was designed
      to evaluate the ability of pregabalin to exert its anticonvulsant effects against
      behavioral and electrographic measures of CNS hyperexcitability associated with
      alcohol withdrawal in a mouse model of ethanol dependence. METHODS: Adult mice
      were chronically exposed to ethanol and, upon withdrawal, were tested for
      behavioral signs of seizure activity (handling-induced convulsions) or
      abnormalities in spontaneous EEG activity recorded from cortical and subcortical
      sites. RESULTS: Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal
      dose dependently reduced severity of handling-induced convulsions in comparison
      to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG
      activity was interrupted by trains of high-voltage synchronous activity in a dose
      related fashion. Finally, pregabalin treatment of repeated withdrawals was
      effective in blocking the development of withdrawal sensitization observed in
      vehicle-treated mice. CONCLUSIONS: Collectively, these results suggest that
      pregabalin may be an effective therapeutic agent for medical management of
      alcohol detoxification.

PMID- 16636011
TI  - Stroke in childhood: experience in Istanbul, Turkey.
AB  - Our objective was to characterize the etiologic factors and outcome for stroke in
      children. We retrospectively reviewed the charts of patients between the ages of
      40 days and 94 months (36.5 +/- 23.7 months) with stroke seen at Istanbul Medical
      Faculty, Department of Pediatrics between January 1995 and December 2003. We
      found 79 cases of stroke: 57 ischemic and 22 hemorrhagic strokes. Seventeen
      children had vitamin K deficiency dependent hemorrhage. In 14 children stroke
      occurred as a complication of cardiac disease, 7 had moyamoya disease, 3 had
      protein C deficiency, 2 had thalassemia, 2 had hyperhomocysteinemia (methylene
      tetrahydrofolate reductase gene mutation), 2 were heterozygote for factor V
      Leiden, 3 had Down's syndrome, 1 was diagnosed with antiphospholipid syndrome, 1
      had glycogen storage disease, and in 28 children no underlying cause could be
      found. Multiple risk factors were found in 4 children. The outcome in all 79
      stroke patients was as follows: asymptomatic 60%; symptomatic epilepsy or
      persistent neurologic deficit 37%; death 3%; and recurrent stroke 5%. Thus, an
      underlying cause for stroke was identified in 65% of the children in the study
      group; 40% of the children either died or suffered motor and/or cognitive
      sequelae.

PMID- 16636012
TI  - Differential expression of inducible nitric oxide synthase and IL-12 between
      peritoneal and splenic macrophages stimulated with LPS plus IFN-gamma is
      associated with the activation of extracellular signal-related kinase.
AB  - Resident peritoneal macrophages (pMphi) are found deficient in T cell-stimulating
      capacity compared with the competent splenic macrophages (sMphi). Macrophages
      (Mphi)-derived nitric oxide (NO) and IL-12 have been shown to play crucial roles
      in the interaction between Mphi and T cells. To further understand differential
      functions between pMphi and sMphi, we focused on the production of NO and IL-12
      from LPS plus IFN-gamma-activated Mphi. We demonstrated the differential
      expression of inducible nitric oxide synthase (iNOS) and IL-12 in pMphi and sMphi
      with LPS plus IFN-gamma stimulation. pMphi produced high level of NO but low
      level of IL-12, whereas sMphi produced high level of IL-12 but no NO.
      Furthermore, we demonstrated that there were no differences in IFN-gamma-induced
      signal transducer and activator of transcription-1 activation and consequent
      interferon regulatory factor-1 and interferon consensus sequence-binding protein
      up-regulation between pMphi and sMphi. Likewise, p38 mitogen-activated protein
      kinase was activated by LPS with identical kinetics in both pMphi and sMphi.
      However, LPS-induced extracellular signal-regulated kinase (ERK) activation was
      prolonged in pMphi comparing with sMphi. Moreover, we demonstrated, using
      inhibitor selective for ERK cascade (PD98059), that the prolonged ERK activation
      contributed a positive signal for iNOS expression and a negative signal for IL
      12p40 expression in resident pMphi. In addition, anti-IL-10-neutralizing antibody
      plus indomethacin could abrogate the inhibitory effects of endogenous IL-10 and
      prostaglandin E2 on the production of IL-12 by resident pMphi possibly through
      suppressing ERK activation. Taken together, profound difference in ERK activation
      may account for differential LPS plus IFN-gamma responsiveness between pMphi and
      sMphi. High production of NO and low production of IL-12 by pMphi may contribute
      to its deficiency in T cell-stimulating capacity.

PMID- 16636013
TI  - LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell.
AB  - Upon antigen recognition by the TCR, both the leukocyte adhesion molecules DNAM-1
      and leukocyte function-associated antigen-1 (LFA-1) associate with lipid rafts
      and form peripheral supra-molecular activation clusters that surround central
      supra-molecular activation clusters at the immunological synapse. The serine
      residue in the cytoplasmic tail of DNAM-1 is responsible for this association of
      DNAM-1 with lipid rafts. The TCR-mediated signal also induces physical
      association of DNAM-1 with LFA-1, for which the serine phosphorylation of DNAM-1
      is also responsible. However, how the serine residue is involved in lipid raft
      recruitment of DNAM-1 has remained unclear. Here, we show that, although the TCR
      mediated signal induced the serine phosphorylation of DNAM-1, DNAM-1 did not
      associate with lipid rafts in CD4+ T cells derived from mice deficient in LFA-1
      expression, indicating that lipid raft recruitment of DNAM-1 depends on LFA-1
      expression. These results suggest that the serine phosphorylation of DNAM-1
      primarily induces physical association of DNAM-1 with LFA-1, which then takes
      DNAM-1 into lipid raft compartment.

PMID- 16636014
TI  - Contributions of mucosal immune cells to methotrexate-induced mucositis.
AB  - The use of high doses of the anti-cancer drug methotrexate (MTX) is associated
      with intestinal damage. As a result, mucosal immune cells become increasingly
      exposed to a vast amount of microbial stimuli. We aimed at determining whether
      these cells are still functional during MTX treatment. Furthermore, we assessed
      if activation of the mucosal immune system would play a role in the pathogenesis
      of mucositis. A contributive role to mucositis for the adaptive immune system was
      established by showing that mucosal lymphocytes from MTX-treated mice secreted
      enhanced amounts of cytokines upon ex vivo polyclonal stimulation. Next, in vitro
      experiments revealed that macrophages were not affected by MTX in the capacity to
      produce tumor necrosis factor-alpha (TNF-alpha) and IL-10 after LPS exposure.
      Moreover, peritoneal macrophages from MTX-treated mice produced more IL-10 and
      TNF-alpha upon LPS stimulation, compared with cells derived from control mice.
      These data indicate a persistence of both innate and adaptive immune responses in
      this model. The clinical relevance of these findings was further established by
      the fact that LPS exposure prior to MTX treatment aggravated the course of
      mucositis. Furthermore, LPS-responsive mice recovered more slowly compared with
      LPS-unresponsive mice from MTX treatment. Finally, we found an increase in weight
      loss and intestinal damage upon MTX treatment in IL-10-deficient mice in
      comparison to wild-type controls, suggesting a protective role for IL-10 in
      mucositis. We conclude that mucosal immune responses remain resilient during MTX
      induced mucositis. Whereas TNF-alpha production may contribute to mucosal damage,
      IL-10 may regulate by restricting excessive mucositis.

PMID- 16636015
TI  - Cathepsin L maturation and activity is impaired in macrophages harboring M. avium
      and M. tuberculosis.
AB  - Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity
      to present antigens via class II MHC molecules. Since successful class II MHC
      restricted antigen presentation relies on the actions of endocytic proteases, we
      asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal
      cysteine proteases-are modulated in macrophages infected with pathogenic
      Mycobacterium spp. Infection of murine bone marrow-derived macrophages with
      either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or
      Cat S activity. In contrast, the activity of Cat L was altered in infected cells.
      Specifically, whereas the 24-kDa two-chain mature form of active Cat L
      predominated in uninfected cells, we observed an increase in the steady-state
      activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the
      enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase
      analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa
      two-chain form was impaired in infected macrophages, and that maturation into the
      24-kDa two-chain form did not occur. Consistent with these data, M. avium
      infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by
      macrophages. Viable bacilli were not required to disrupt Cat L maturation,
      suggesting that a constitutively expressed mycobacterial component was
      responsible. The absence of the major active form of lysosomal Cat L in M. avium-
      and M. tuberculosis-infected macrophages may influence the types of T cell
      epitopes generated in these antigen-presenting cells, and/or the rate of class II
      MHC peptide loading.

PMID- 16636016
TI  - Phosphatidylinositol 3-kinase improves the efficiency of positive selection.
AB  - We have generated transgenic mice expressing the amino-terminal fragment of the
      phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110ABD) in thymocytes.
      Expression of p110ABD results in constitutive activation of PI3K and in
      significant increases in the numbers of mature, single-positive thymocytes. We
      previously reported that the increase in mature cells was in part due to a defect
      in thymic emigration. In this study we identify another component to this
      phenotype. Expression of p110ABD results in an enhancement of positive selection,
      without alterations in thymocyte lifespan or negative selection. Since PI3K can
      affect activation of Btk, which in turn potentiates calcium fluxes, during B cell
      development, our results suggest that PI3K could play a role in the regulation of
      Itk kinases in T cells, and that both cell types share a common signaling network
      to modulate calcium responses downstream of their antigen receptor.

PMID- 16636017
TI  - Proinflammatory changes in human umbilical cord vein endothelial cells can be
      induced neither by native nor by modified CRP.
AB  - The role of C-reactive protein (CRP) in atherosclerosis is controversial. It is
      not clear, either, if the presumed endothelium-activating effect of CRP resides
      in native CRP (nCRP) or in a conformational isoform of CRP known as modified CRP
      (mCRP). In the present study we evaluated and compared the effect of nCRP,
      recombinant modified CRP (rmCRP) and urea-modified CRP (umCRP) on human umbilical
      vein endothelial cells (HUVECs). CRP preparations were carefully analyzed by
      biochemical, immunological and cell biological methods in order to avoid
      endotoxin or sodium azide contamination as well as inappropriate conformational
      changes, which together had possibly been the main reason for the previously
      published controversial results. Neither nCRP nor mCRP showed significant
      cytotoxicity up to 100 microg ml(-1) at 24 h but high concentrations of CRPs
      induced cell death at 48 h. rmCRP but not nCRP nor umCRP showed membrane binding
      to HUVEC by confocal microscopy. However, none of the CRP forms induced
      intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, E
      selectin expression or IL-8 production. Monocyte chemotactic protein-1 production
      was weakly inhibited by high concentration of both nCRP and rmCRP, analyzed by
      sandwich ELISA. Neither nCRP nor mCRP could induce pro-inflammatory changes in
      the phenotype of HUVECs. Therefore, our present findings do not support the
      notion that different isoforms of CRP alone have significant effects on
      inflammation of the vessel wall via an interaction with endothelial cells (ECs),
      although one cannot exclude the possibility that there may be significant
      differences among various types of ECs in the response to CRP.

PMID- 16636018
TI  - Transjugular liver biopsy: how good is it for accurate histological
      interpretation?
AB  - BACKGROUND: A transjugular liver biopsy (TJLB) specimen is often smaller or more
      fragmented than a percutaneous liver biopsy (PLB) specimen. Recently, for PLB,
      the minimum requirements to evaluate chronic hepatitis have been set at 20-25 mm
      length and > or =11 complete portal tracts. AIM: To evaluate and compare length
      of TJLB and PLB specimens, portal tract number, fragmentation and adequacy for
      histopathological diagnosis and staging. PATIENTS AND METHODS: 326 consecutive
      TJLB specimens in 274 patients (109 who had undergone a transplantation), always
      using three passes (19-G Tru-cut) and 40 consecutive PLB specimens (15-G
      Menghini). RESULTS: No technical failures occurred with the TJLB, and
      histological diagnosis was possible in 98.5%. The median (range) number of
      fragments was 5 (1-13) and the median total length was 22 (3-46) mm, with 65% of
      specimens > or =20 mm and 36% > or =25 mm; 60% of TJLB specimens were > or =28 mm
      long had > or =11 complete portal tracts. No difference in complete portal tract
      number or biopsy length was found between PLB and TJLB specimens. CONCLUSION: A
      TJLB specimen with three passes is adequate for histological diagnosis, with 89%
      of specimens being either > or =15 mm or having > or =6 complete portal tracts.
      Although adequate sampling remains a limitation for staging and grading of
      chronic hepatitis, TJLB is comparable to PLB in this respect.

PMID- 16636019
TI  - Identification of mismatch repair gene mutations in young patients with
      colorectal cancer and in patients with multiple tumours associated with
      hereditary non-polyposis colorectal cancer.
AB  - BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with
      multiple tumours associated with hereditary non-polyposis colorectal cancer
      (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR)
      gene mutations. AIM: To analyse the value of family history, microsatellite
      instability (MSI) analysis and MMR protein staining in the tumour to predict the
      presence of an MMR gene mutation in such patients. METHODS: In 281 patients
      diagnosed with CRC before the age of 50 years or with CRC and at least one
      additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and
      MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex
      ligation-dependent probe amplification. MSI analysis with five consensus markers
      and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours.
      RESULTS: 25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found.
      MSI analysis missed three and immunohistochemistry (IHC) missed two mutation
      carriers. Sensitivities of family history, MSI analysis and IHC for the presence
      of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and
      positive predictive values were 19%, 23% and 38%, respectively. Multivariate
      analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0
      to 184). Prevalence of pathogenic germline MMR gene mutations in patients with
      CRC before the age of 50 years was 6% and in those with > or =2 HNPCC-associated
      tumours was 22%. In the second group, no mutation carriers were found among the
      29 patients who were diagnosed with their first tumour after the age of 60 years.
      CONCLUSION: Family history, MSI analysis and IHC are indicative parameters to
      select patients with CRC for MMR gene mutation analysis. The data show that IHC
      is the best single selection criterion.

PMID- 16636020
TI  - Ischaemia induces paradoxical changes in axonal excitability in end-stage kidney
      disease.
AB  - Peripheral neuropathy is present in 65% of patients with end-stage kidney disease
      (ESKD). No cause is yet established: nerve excitability studies have shown that
      axons are chronically depolarized, primarily owing to hyperkalaemia, but in vitro
      studies have suggested a role for axonal Na+/K+ pump dysfunction. To investigate
      Na+/K+ pump activity in vivo, lower limb ischaemia was induced in five ESKD
      patients and six healthy controls by a sphygmomanometer cuff, inflated to 200 mm
      Hg and maintained for 13 min. The peroneal nerve was stimulated at the fibular
      neck and excitability parameters were recorded from tibialis anterior (TA) and
      extensor digitorum brevis (EDB) before, during and after the ischaemic period.
      Baseline excitability studies in ESKD patients demonstrated reductions in
      threshold electrotonus and superexcitability and increased refractoriness,
      consistent with membrane depolarization. During ischaemia, threshold increased in
      ESKD patients [by +23.6 +/- 5.0% (TA); +32.1 +/- 7.3% (EDB)] in contrast to the
      persistent threshold reduction observed in normal controls [-2.4 +/- 5.2% (TA); 
      13.0 +/- 8.2% (EDB); P < 0.01]. These changes were accompanied by increased
      refractoriness and reduced superexcitability in both ESKD and control groups,
      consistent with ischaemic depolarization. Conversely, there was reduction in
      strength-duration time constant towards the end of ischaemia. Following release
      of ischaemia, the marked increase in threshold observed in normal controls was
      not evident in ESKD patients, but the rapid return of threshold to baseline
      argues against significant Na+/K+ pump dysfunction. The abnormal pattern of
      response to ischaemia in the ESKD patients was not fully explained by the
      hyperkalaemic membrane depolarization and suggests that another dialysable factor
      affects nerve excitability in ESKD patients, most likely H(+) ions, but that this
      factor only becomes evident during ischaemia. Blockade of persistent Na+
      conductances by H+ would also explain the reduction in strength-duration time
      constant observed during ischaemia.

PMID- 16636021
TI  - Increased thalamic neurodegeneration following ischaemic cortical stroke in
      osteopontin-deficient mice.
AB  - Inflammation aggravates brain injury caused by stroke and neurodegeneration.
      Osteopontin (OPN) is a cytokine-like glycoprotein that binds to various integrins
      and CD44 variants. OPN exerts proinflammatory effects in autoimmune conditions
      but also has cytoprotective properties and participates in wound healing. In this
      study, we addressed the role of OPN in ischaemic brain injury using OPN knock-out
      (KO) mice in models of cortical stroke. Compared with wild-type animals, OPN KO
      mice exhibited unaltered infarct development at the primary injury site but
      greatly increased retrograde degeneration of the ipsilateral thalamus. Thalamic
      neurodegeneration in OPN-deficient mice was associated with pronounced microglia
      activation and inflammatory gene expression and could be attenuated via
      pharmacological blockade of the inducible nitric oxide synthase (iNOS).
      Therefore, delayed neurodegeneration in OPN-deficient mice was at least partly
      due to an excessive release of nitric oxide via the iNOS pathway. Neuroprotective
      and anti-inflammatory effects of OPN may be relevant for a variety of
      neurological disease conditions.

PMID- 16636022
TI  - The value of animal models for drug development in multiple sclerosis.
AB  - The rodent model for multiple sclerosis, experimental allergic (autoimmune)
      encephalomyelitis (EAE), has been used to dissect molecular mechanisms of the
      autoimmune inflammatory response, and hence to devise and test new therapies for
      multiple sclerosis. Clearly, artificial immunization against myelin may not
      necessarily reproduce all the pathogenetic mechanisms operating in the human
      disease, but most therapies tested in multiple sclerosis patients are
      nevertheless based on concepts derived from studies in EAE. Unfortunately,
      several treatments, though successful in pre-clinical EAE trials, were either
      less effective in patients, worsened disease or caused unexpected, severe adverse
      events, as we review here. These discrepancies must, at least in part, be due to
      genetic and environmental differences, but the precise underlying reasons are not
      yet clear. Our understanding of EAE pathogenesis is still incomplete and so,
      therefore, are any implications for drug development in these models. Here, we
      suggest some potential explanations based on new thinking about key pathogenic
      concepts and differences that may limit extrapolation from EAE to multiple
      sclerosis. To try to circumvent these rodent-human dissimilarities more
      systematically, we propose that pre-clinical trials should be started in
      humanized mouse models.

PMID- 16636023
TI  - Can sutures get wet? Prospective randomised controlled trial of wound management
      in general practice.
AB  - OBJECTIVE: To compare standard management of keeping wounds dry and covered with
      allowing wounds to be uncovered and wet in the first 48 hours after minor skin
      excision. DESIGN: Prospective, randomised controlled, multicentre trial testing
      for equivalence of infection rates. SETTING: Primary care in regional centre,
      Queensland, Australia. PARTICIPANTS: 857 patients randomised to either keep their
      wound dry and covered (n = 442) or remove the dressing and wet the wound (n =
      415). RESULTS: The incidence of infection in the intervention group (8.4%) was
      not inferior to the incidence in the control group (8.9%) (P < 0.05). The one
      sided 95% confidence interval for the difference of infection rates was infinity
      to 0.028. CONCLUSION: These results indicate that wounds can be uncovered and
      allowed to get wet in the first 48 hours after minor skin excision without
      increasing the incidence of infection.

PMID- 16636024
TI  - Gender ratio and the specialty of anesthesia.

PMID- 16636025
TI  - Scoring systems for the critically ill: use, misuse and abuse.

PMID- 16636026
TI  - Gender patterns amongst Canadian anesthesiologists.
AB  - PURPOSE: The specialty of anesthesiology in Canada has traditionally had a larger
      proportion of male practitioners. More recently, however, the proportion of
      female medical students has increased. We sought to determine if the gender ratio
      within the specialty of anesthesiology in Canada has followed the female:male
      distribution patterns within medical schools. METHODS: Gender-specific data were
      obtained from the Royal College of Physicians and Surgeons of Canada, the
      Canadian Institute for Health Information, the Canadian Residency Matching
      Service (CaRMS), and the Program Director from each of the 16 Canadian
      Anesthesiology Residency Training Programs. RESULTS: The ratio of practicing
      female:male anesthesiologists increased from 0.29:1 in 1998 to 0.34:1 in 2005.
      The ratio was greatest in the youngest age grouping (< 45 yr), at 0.49:1, and
      lowest in the > 64 age group, at 0.16:1. As of the 2004-2005 academic year, there
      were 201 women in a Canadian anesthesiology residency program vs 316 males, a
      female:male ratio of 0.64:1. Female medical students were less likely to rank
      anesthesiology residency as their first choice in the annual CaRMS match as
      compared to their male counterparts; a mean of 21 female medical students ranked
      an English anesthesiology residency program as their first choice in the CaRMS
      match, vs a mean of 35 males, from 1993-2005 (inclusive). CONCLUSIONS: The number
      (and female:male ratio) of women in anesthesiology in Canada is increasing
      gradually. However, more males continue to enter the field than women. This may
      be explained by a lower number of women who rank anesthesiology as their first
      choice in the annual CaRMS match.

PMID- 16636027
TI  - Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.
AB  - PURPOSE: N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are
      closely related with the excitability of pyramidal neurons and PFC function. As
      the effect of thiopental sodium on the central nervous system may partly result
      from the inhibition of PFC NMDA receptors, we investigated the effect of
      thiopental sodium with different concentrations on NMDA-gated currents in acutely
      dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental
      sodium inhibits NMDA receptor function. METHODS: Three to four week old male
      Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons
      from the PFC were prepared and standard whole-cell patch clamp recordings were
      performed. Escalating concentrations from 3-1000 microM NMDA were applied 100
      microm from the pyramidal cells, and the concentration in the effect compartment
      related to 50% effect (EC50) of NMDA was determined for the ensuing experiments.
      One hundred microM NMDA alone (control) or NMDA with different concentrations (10
      1000 microM) of thiopental sodium were applied. After the inhibitory
      concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established
      this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal
      cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was
      determined. RESULTS: N-methyl-D-aspartate induced inward currents in a
      concentration-dependent manner, which were completely antagonized by 50 microM
      AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50
      of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was
      inhibited by thiopental sodium in a concentration-dependent manner, and the IC50
      of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM
      thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/-
      0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The
      EC50 of NMDA was 128 +/- 15 microM, which was greater than that of NMDA without
      thiopental sodium (P < 0.01). CONCLUSIONS: Thiopental sodium decreases NMDA-gated
      currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a
      concentration-dependent manner.

PMID- 16636028
TI  - Anesthesiologist-controlled versus patient-controlled propofol sedation for
      shockwave lithotripsy.
AB  - PURPOSE: To compare anesthesiologist-controlled sedation (ACS) with patient
      controlled sedation (PCS), with respect to propofol requirements, sedation, and
      recovery, in patients undergoing extracorporeal shockwave lithotripsy for urinary
      calculi. METHODS: Sixty-four patients were randomized, in this double-blind
      study, to receive propofol sedation according to one of two regimens: infusion of
      200 microg.kg(-1) .min(-1) for ten minutes reduced thereafter to 50-150
      microg.kg(-1) .min(-1) titrated by an anesthesiologist, according to patient
      response (group ACS), or propofol administered by patient-controlled analgesia
      (bolus dose 300 microg.kg(-1), lockout interval three minutes, no basal
      infusion), (group PCS). All patients received midazolam 10 microg.kg(-1) iv and
      fentanyl 1 microg.kg(-1) iv preoperatively, followed by fentanyl infused at a
      rate of 0.5 microg.kg(-1) .hr(-1) throughout the procedure. Sedation and
      analgesia were assessed using the A-line ARX index and visual analogue scale,
      respectively. Psychomotor recovery and readiness for recovery room discharge were
      assessed using the Trieger dot test and postanesthesia discharge score,
      respectively. Patient satisfaction was assessed on a seven-point scale (1-7).
      RESULTS: In comparison to group PCS, patients in group ACS received more propofol
      (398 +/- 162 mg vs 199 +/- 68 mg, P < 0.001), were more sedated (A-line ARX
      index: 35 +/- 16 vs 73 +/- 16, P < 0.001), experienced less pain (visual analogue
      scale: 0 +/- 0 vs 3 +/- 1, P < 0.001), and were more satisfied (median [Q1, Q3]:
      7 [7, 7] vs 6 [6, 7], P < 0.001). In contrast, patients in group PCS had faster
      psychomotor recovery (Trieger dot test median [Q1, Q3]: 8 [4, 16] vs 16 [12, 26]
      dots missed, P = 0.002) and achieved postanesthesia discharge score >/=9 earlier
      (median [Q1, Q3]: 40 [35, 60] vs 88 [75, 100] min, P < 0.001) compared with group
      ACS. CONCLUSION: In comparison to PCS for patients undergoing extracorporeal
      shockwave lithotripsy, propofol/fentanyl ACS is associated with increased
      propofol administration, deeper sedation levels, and greater patient comfort.
      However, ACS is associated with slower recovery and a longer time to meet
      discharge criteria, when compared to PCS.

PMID- 16636029
TI  - Doxapram shortens recovery following sevoflurane anesthesia.
AB  - PURPOSE: A randomized, double blind controlled trial was undertaken to
      investigate the effect of doxapram on recovery times and bispectral index
      following sevoflurane anesthesia. METHODS: Upon completion of surgery under
      sevoflurane anesthesia, 60 adult patients were randomly allocated to receive
      either doxapram hydrochloride 1 mg.kg(-1) iv or saline placebo. Clinical recovery
      from anesthesia was assessed by time to eye opening on verbal command, hand
      squeezing on command, time to extubation, and the Aldrete recovery score.
      Bispectral index values, systolic blood pressure, and heart rate were recorded at
      baseline (before anesthesia), during surgery, and every minute for 15 min after
      administration of the study drug. RESULTS: Time to eye opening was shorter in the
      doxapram group compared with the control group (6.9 +/- 2.2 min vs 9.9 +/- 3.1
      min, P < 0.05). Mean bispectral index scores were also higher in the doxapram
      group compared with the saline placebo seven to eight minutes following
      administration of the study medication (P < 0.05). More rapid emergence was
      associated with a greater increase in heart rate with doxapram (P < 0.05 compared
      with placebo), but no differences in systolic blood pressure responses were
      observed in comparison with placebo. CONCLUSION: We conclude that doxapram 1
      mg.kg(-1) hastens early recovery from sevoflurane anesthesia, and this arousal
      effect correlates with higher bispectral index values.

PMID- 16636030
TI  - Preoperative gabapentin for postoperative analgesia: a meta-analysis.
AB  - PURPOSE: Gabapentin's role in the treatment of chronic neuropathic pain is well
      known. What is less well established is its role for managing postoperative pain.
      In order to clarify whether gabapentin's utility in acute pain control is more
      than just theoretical, we conducted a meta-analysis of all randomized trials that
      addressed gabapentin's role in acute postoperative pain control. We specifically
      addressed whether gabapentin reduces pain scores, analgesia consumption, and/or
      analgesia-related side effects in the first 24 hr following surgery. SOURCE: We
      identified eight placebo-controlled, randomized controlled trials and conducted a
      meta-analysis using the primary outcomes of pain scores, total analgesia
      consumption, and side effects over a 24-hr period. PRINCIPLE FINDINGS: Patients
      who received gabapentin preoperatively reported significantly lower pain scores (
      11.9 at rest and -11.0 with movement on a 100-point visual analogue scale) and
      opioid consumption (-14.7 mg of morphine in 24 hr) with no difference in the
      incidence of side effects. CONCLUSION: Although gabapentin given preoperatively
      decreases pain scores and analgesic consumption in the first 24 hr after surgery,
      the clinical significance of this finding has yet to be determined. This meta
      analysis could not demonstrate a significant reduction in the incidence of side
      effects. Due to the small numbers enrolled in the studies, larger randomized
      control trials are warranted.

PMID- 16636031
TI  - The effects of botulinum toxin A on mechanical and cold allodynia in a rat model
      of neuropathic pain.
AB  - PURPOSE: Botulinum toxin type A (BoNT-A) has been used to treat many disorders
      related to excessive muscle contraction, but there are few studies evaluating its
      effects on neuropathic pain. The aim of this study was to evaluate the analgesic
      effects of BoNT-A in a rat model of neuropathic pain. METHODS: Male Sprague
      Dawley rats were prepared by ligating the left L5 and L6 spinal nerves to produce
      neuropathic pain. Seventy neuropathic rats were randomly assigned into seven
      groups. Either normal saline or BoNT-A (10, 20, 30 and 40 U.kg(-1)) was
      administered to the plantar surface of the affected left hind paw, and BoNT-A (30
      and 40 U.kg(-1)) was administered into the unaffected right paw in order to
      determine the drug-induced systemic effect. Mechanical and cold allodynia were
      observed at pre-administration, one, three, five, seven and 15 days after drug
      administration, and were quantified by measuring withdrawal frequencies to
      stimuli with von Frey filament and 100% acetone, respectively. Rotarod
      performance was measured to detect drug-induced adverse motor effects. RESULTS:
      The mean minimum withdrawal frequencies to mechanical and cold stimuli were 77 +/
      11 and 90 +/- 4.5%, 46 +/- 5 and 66 +/- 7%, 33 +/- 7 and 62 +/- 7%, 12 +/- 2.9
      and 54 +/- 7.3% with 10, 20, 30 and 40 U.kg(-1) BoNT-A respectively (P < 0.05).
      Doses of 30 and 40 U.kg(-1) BoNT-A resulted in reduced rotarod performance time.
      CONCLUSION: We conclude that peripherally administered BoNT-A reduces mechanical
      and cold allodynia in a rat model of neuropathic pain.

PMID- 16636032
TI  - Cesarean section in a patient with familial cardiomyopathy and a cardioverter
      defibrillator.
AB  - PURPOSE: To describe the impact of maternal automatic implantable cardioverter
      defibrillator (AICD) therapy on pregnancy outcome, and discuss the clinical
      rationale for regional anesthesia in parturients with AICDs. CLINICAL FEATURES: A
      20-yr-old primigravida with a history of familial cardiomyopathy and AICD
      placement presented at 39 weeks gestational age for elective labour induction.
      Ultimately, the patient underwent a Cesarean section for a failed induction. Her
      AICD was deactivated during the peripartum period, although the pacing function
      remained active as she had an underlying heart rhythm of less than 34 beat.min(
      1). The patient had continuous electrocardiogram monitoring via an external
      defibrillating unit to which she remained connected by external defibrillator
      pads. Labour analgesia and surgical anesthesia were provided with a lumbar
      epidural dosed with varying concentrations of bupivacaine. This management
      resulted in an excellent maternal and fetal outcome. CONCLUSIONS: Automatic
      implantable cardioverter-defibrillators are being utilized more frequently in the
      obstetric population, and appear compatible with good fetal outcomes. Experience
      with the anesthetic management of these patients is markedly limited - primarily
      involving reports of general anesthesia for Cesarean section. Epidural
      anesthesia, however, offers distinct advantages in this patient population
      including easy conversion from labour analgesia to surgical anesthesia,
      preservation of fetal-maternal hemodynamics, prevention of increases in plasma
      catecholamines due to labour or operative pain, and, finally, possible direct
      suppression of arrhythmias by pharmacologically-active plasma levels of local
      anesthetic.

PMID- 16636033
TI  - Anesthetic management of a parturient with carnitine palmitoyltransferase II
      deficiency.
AB  - PURPOSE: To report the anesthetic management of a patient with carnitine
      palmitoyltransferase II deficiency who presented for labour and delivery.
      CLINICAL FEATURES: A 30-yr-old primiparous woman with known carnitine
      palmitoyltransferase II deficiency and a past history of exercise induced muscle
      pain, weakness and myoglobinuria presented in active labour. Management consisted
      of an early epidural for labour and continuous dextrose infusion with frequent
      blood sugar monitoring. She had an uneventful spontaneous vaginal delivery. She
      experienced a single asymptomatic episode of hypoglycemia on the first postpartum
      day. Her serum creatine kinase was six times normal at 24 hr post-delivery and
      remained elevated for three days without evidence of rhabdomyolysis. The
      remainder of her postpartum course was uneventful. CONCLUSION: Labour and
      delivery is a potential precipitant of rhabdomyolysis in patients with carnitine
      palmitoyltransferase II deficiency. The normal postpartum creatine kinase
      elevation (two to four times baseline at 24 hr) must be taken into account when
      monitoring these patients. On the basis of the physiologic principles,
      institution of early epidural analgesia to blunt the stress response to labour
      and delivery, continuous dextrose infusion and frequent glucose monitoring during
      labour and postpartum are the mainstays of management.

PMID- 16636034
TI  - Anesthetic and obstetric considerations in a parturient with Klippel-Trenaunay
      syndrome.
AB  - PURPOSE: To explain the considerations governing the anesthetic management of
      pregnant patients with Klippel-Trenaunay syndrome (KTS). Klippel-Trenaunay
      syndrome is a congenital vascular disease characterized by cutaneous hemangiomas,
      venous varicosities, and limb hypertrophy; and is associated with both
      hemorrhagic and thrombotic complications. The importance of this diagnosis,
      including the presence of neuraxial vascular anomalies, is often under
      appreciated by both obstetric and anesthesia providers. While regional anesthetic
      management of patients with KTS has been discussed by others, we present a case
      in which regional anesthesia presented an unwarranted risk to the patient.
      CLINICAL FEATURES: An obese, 18-yr-old parturient with a fetus in the breech
      position underwent Cesarean delivery at 35 weeks gestation secondary to evolving
      preeclampsia. Unfortunately, no neurovascular imaging of this patient's spine was
      available. The patient underwent an attempted external cephalic version, a failed
      obstetric induction, and, ultimately, a Cesarean delivery under general
      anesthesia. The resulting infant was without any stigmata of KTS. Both mother and
      infant did well during the course of their hospitalization, and were discharged
      home without incident. CONCLUSIONS: The posterior cutaneous hemangiomas of KTS
      may be associated with underlying epidural and subdural vascular malformations.
      Disruption of these vascular anomalies during regional anesthesia may lead to
      neuraxial hematoma formation, which may be further compounded by a consumptive
      coagulopathy observed in some cases of KTS. If neuraxial vascular anomalies
      cannot be ruled out radiographically, regional anesthesia should be avoided.
      Additionally, regardless of the anesthetic technique chosen, the coagulation
      profile of these patients should be verified for signs of coagulopathy.

PMID- 16636035
TI  - Patient-controlled versus nurse-controlled analgesia after cardiac surgery--a
      meta-analysis.
AB  - BACKGROUND: Patient-controlled analgesia (PCA) has been advocated as superior to
      conventional nurse-controlled analgesia (NCA) with less risk to patients. This
      systematic review and meta-analysis sought to determine whether PCA improves
      clinical and resource outcomes when compared with NCA. METHODS: A comprehensive
      search was undertaken to identify all randomized controlled trials of PCA vs NCA.
      Medline, Cochrane Library, Embase, and conference abstract databases were
      searched from the date of their inception to August 2005. The primary
      postoperative outcome was defined as mean visual analogue scale (VAS) scores.
      Secondary postoperative outcomes included cumulative morphine equivalents,
      intensive care unit (ICU) and hospital length of stay, postoperative nausea and
      vomiting, sedation, respiratory depression, and all-cause mortality. Odds ratios
      or weighted mean differences (WMD) and their 95% confidence intervals (CI) were
      calculated for discrete and continuous outcomes, respectively. RESULTS: Ten
      randomized trials involving 666 patients were included. Compared to NCA, PCA
      significantly reduced VAS at 48 hr (WMD -0.73, 95% CI -1.19, -0.27), but not at
      24 hr (WMD -0.19, 95% CI -0.61, 0.24). Cumulative morphine equivalents consumed
      were significantly increased at 24 hr (WMD 6.84 mg, 95% CI 0.97, 12.72 mg), and
      at 48 hr (WMD 10.46 mg 95% CI 2.02, 18.9 mg) for PCA compared with NCA.
      Ventilation times, length of ICU stay, length of hospital stay, patient
      satisfaction scores, sedation scores, and incidence of postoperative nausea and
      vomiting, respiratory depression, severe pain, discontinuations, and death were
      not significantly different between groups, but these outcomes were generally
      under-reported. CONCLUSIONS: In postcardiac surgical patients, PCA increases
      cumulative 24 and 48 hr morphine consumption, and improves 48-hr VAS compared
      with NCA.

PMID- 16636036
TI  - Prognostic value of postoperative proteinuria in cardiac surgery: a pilot study.
AB  - BACKGROUND: Proteinuria is a non-specific marker of inflammation that may reflect
      the glomerular component of systemic capillary leak. The objective of this pilot
      study was to determine if postoperative proteinuria is associated with adverse
      outcomes following cardiac surgery with cardiopulmonary bypass. METHODS: Eligible
      patients were individuals undergoing cardiac surgery with cardiopulmonary bypass
      who did not have severe pre-existing renal dysfunction. Urine was collected after
      induction of anesthesia (baseline) and two to four hours after arrival to the
      intensive care unit (ICU). Proteinuria was measured as random protein creatinine
      ratio in g.mol(-1). Adverse events were defined a priori as prolonged ICU stay (>
      or = 90th percentile) and organ dysfunction. The relationship between proteinuria
      and adverse events was assessed by bivariate (Chi-square or Fisher's exact tests)
      and multivariable (multiple logistic regression) analyses. RESULTS: The study
      included 197 (of 243 eligible) patients. Postoperative proteinuria (protein
      creatinine ratio > or = 30 g.mol(-1)) was associated with prolonged (> or = four
      days) ICU stay [odds ratio (OR) 7.0; 95% confidence interval (CI) 2.8-17.1] and
      organ dysfunction (OR 3.9; CI 1.9-8.1). After adjustment for confounders,
      proteinuria was associated with a 3.2-fold increase in the odds of both prolonged
      ICU stay (CI 1.1-9.7) and organ dysfunction (CI 1.4-7.0). CONCLUSIONS:
      Proteinuria two to four hours after cardiac surgery with cardiopulmonary bypass
      may be a useful marker for systemic capillary leak and adverse postoperative
      events. Large prospective studies are needed to confirm these findings.

PMID- 16636037
TI  - Extubation of the surgically resected airway--a role for remifentanil and
      propofol infusions.
AB  - PURPOSE: To report the use of propofol and remifentanil infusions to facilitate
      smooth extubation of a surgically resected airway. CLINICAL FEATURES: A 19-yr-old
      man weighing 85 kg was scheduled for tracheal resection surgery following
      postintubation tracheal stenosis. He had a relatively long segment (4 cm) of his
      trachea resected and anastomosed. Postoperatively, he was sedated and electively
      ventilated for four days in a chin to chest position by stay sutures. In order to
      reduce any risk of traumatic disruption to the tracheal anastomosis, we planned
      to extubate his trachea under light general anesthesia. Attempts to extubate his
      trachea using propofol and alfentanil infusions failed. We used propofol and
      remifentanil infusions to achieve a state of sedate cooperation and extubated his
      trachea with fibreoptic bronchoscope guidance. CONCLUSION: Propofol and
      remifentanil infusions in combination can facilitate successful extubation of the
      surgically resected airway with high risk of disruption.

PMID- 16636038
TI  - Laryngoscopic evaluation with the Airway Cam.
AB  - PURPOSE: The Airway Cam is a head-mounted direct laryngoscopy video system which
      uses a prismatic sighting system that aligns with the operator's line of sight.
      This study evaluated intra- and inter-observer consistency in laryngoscopy
      grading comparing direct laryngoscopy to the laryngoscopy grade obtained with the
      Airway Cam. METHODS: Twenty-seven patients receiving a general anesthetic for
      elective surgery had laryngoscopy performed by an anesthesiologist wearing the
      Airway Cam. Each video was duplicated, then randomized and reviewed in a blinded
      fashion by the original laryngoscopist and a second anesthesiologist. Intra- and
      inter-observer correlations were identified. RESULTS: There was good intra
      observer agreement of the Cormack-Lehane scale between direct laryngoscopy and
      laryngoscopy recorded with the Airway Cam (kappa = 0.63). The corresponding intra
      observer correlation of the percentage of glottic opening score was strong at r =
      0.83. There was good inter-observer agreement of the Cormack-Lehane scale between
      direct laryngoscopy and that observed by the second anesthesiologist during
      Airway Cam video review (kappa = 0.70). There was moderate correlation of the
      inter-observer percentage of glottic opening scores (r = 0.73). CONCLUSION: This
      study validates that the view recorded by the Airway Cam reflects the view of the
      laryngoscopist. The Airway Cam may introduce an additional level of objectivity
      into airway management research and teaching.

PMID- 16636039
TI  - Images in anesthesia: echo contrast as an adjunct to intraoperative angiography
      in the detection of endoleaks.

PMID- 16636040
TI  - The logistic organ dysfunction score as a tool for making ethical decisions.
AB  - PURPOSE: We examined whether the change of the logistic organ dysfunction score
      (LOD) between the first and the fourth day in the intensive care unit (ICU) could
      be predictive of death in the ICU. The LOD could then be used to help make
      decisions concerning therapeutic limitations (TL). METHODS: One hundred fifty
      four patients were included. Exclusion criteria were: discharge from the ICU or
      TL before the 72nd hr. Ninety-three patients remained for evaluation. The LOD was
      calculated on the day of admission (LOD1) and between the 72nd and 96th hr
      (LOD4). The DeltaLOD = LOD4-LOD1 index was calculated for survivors and non
      survivors; sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) were calculated. RESULTS: Sixteen patients died in the
      ICU, they had a higher DeltaLOD (0 vs -2; P = 0.0046) than the survivors. After
      logistic regression, a high DeltaLOD was associated with a higher risk of death
      in the ICU independent of the initial severity of disease. The PPV concerning
      death in the ICU was 0.66 for a DeltaLOD > or = 4 cut-off. The NPV was 0.89 for a
      cut-off of > or = 1. CONCLUSION: DeltaLOD appears to be a predictor of death in
      the ICU, independent of the initial severity of disease. The PPV is not high
      enough to assist with making individual TL decisions. The NPV can help to
      identify patients at low risk of death. The DeltaLOD deserves to be evaluated in
      a population exhibiting greater severity of disease.

PMID- 16636041
TI  - Best evidence in critical care medicine: central venous catheterization: the
      impact of insertion site.

PMID- 16636042
TI  - Epiglottic hematoma: a rare occurrence after tracheal intubation.

PMID- 16636043
TI  - Morbidity in a pediatric patient having alcohol ablation of an arteriovenous
      malformation.

PMID- 16636044
TI  - Thromboelastographic monitoring of the efficacy of recombinant factor VIIa
      administration in a parturient with factor VII deficiency.

PMID- 16636045
TI  - [Management of postoperative pain in Togo: knowledge and attitude of
      prescribers].

PMID- 16636046
TI  - The Mechanism of nucleotide-assisted molybdenum insertion into molybdopterin. A
      novel route toward metal cofactor assembly.
AB  - The molybdenum cofactor (Moco) is synthesized by an ancient and conserved
      biosynthetic pathway. In plants, the two-domain protein Cnx1 catalyzes the
      insertion of molybdenum into molybdopterin (MPT), a metal-free phosphorylated
      pyranopterin carrying an ene-dithiolate. Recently, we identified a novel
      biosynthetic intermediate, adenylated molybdopterin (MPT-AMP), which is
      synthesized by the C-terminal G domain of Cnx1. Here, we show that MPT-AMP and
      molybdate bind in an equimolar and cooperative way to the other N-terminal E
      domain (Cnx1E). Tungstate and sulfate compete for molybdate, which demonstrates
      the presence of an anion-binding site for molybdate. Cnx1E catalyzes the Zn(2+)
      /Mg(2+)-dependent hydrolysis of MPT-AMP but only when molybdate is bound as co
      substrate. MPT-AMP hydrolysis resulted in stoichiometric release of Moco that was
      quantitatively incorporated into plant apo-sulfite oxidase. Upon Moco formation
      AMP is release as second product of the reaction. When comparing MPT-AMP
      hydrolysis with the formation of Moco and AMP a 1.5-fold difference in reaction
      rates were observed. Together with the strict dependence of the reaction on
      molybdate the formation of adenylated molybdate as reaction intermediate in the
      nucleotide-assisted metal transfer reaction to molybdopterin is proposed.

PMID- 16636047
TI  - Identification of proteins cleaved downstream of caspase activation in monocytes
      undergoing macrophage differentiation.
AB  - We have shown previously that caspases were specifically involved in the
      differentiation of peripheral blood monocytes into macrophages while not required
      for monocyte differentiation into dendritic cells. To identify caspase targets in
      monocytes undergoing macrophagic differentiation, we used the human monocytic
      leukemic cell line U937, whose macrophagic differentiation induced by exposure to
      12-O-tetradecanoylphorbol 13-acetate (TPA) can be prevented by expression of the
      baculovirus caspase-inhibitory protein p35. A comparative two-dimensional gel
      proteomic analysis of empty vector- and p35-transfected cells after 12 h of
      exposure to 20 nm TPA, followed by mass spectrometry analysis, identified 38
      differentially expressed proteins. Those overexpressed in p35-expressing cells (n
      = 16) were all full-length, whereas half of those overexpressed in control cells
      (n = 22) were N- or C-terminal cleavage fragments. The cleavage or degradation of
      seven of these proteins was confirmed in peripheral blood monocytes undergoing
      macrophage colony-stimulating factor-induced macrophagic differentiation. In U937
      cells exposed to TPA, these proteolytic events can be inhibited by expression of
      a caspase-8 dominant negative mutant or the cowpox virus CrmA caspase inhibitor.
      These cleavages provide new insights to analyze the role of caspases in this
      specific differentiation program.

PMID- 16636048
TI  - Stat3 cleavage by caspases: impact on full-length Stat3 expression, fragment
      formation, and transcriptional activity.
AB  - Stat3 and its isoforms belong to a family of cytoplasmic transcription factors
      that affect the synthesis of various proteins. Caspases are cysteinyl-aspartate
      proteases that function under apoptotic and non-apoptotic conditions. We now
      report that, in addition to transcriptional splicing, Stat3 fragmentation can be
      mediated by caspases. Caspase activation in DU145 cells was achieved by
      staurosporine (STS) exposure, and Western analysis revealed a reduction in full
      length Stat3 (fl-Stat3) expression that was caspase-mediated. This proteolytic
      relationship was further studied by exposing purified Stat3 protein to a mixture
      of active caspases under cell-free conditions. This demonstrated that caspases
      directly cleaved Stat3 and Stat3 cleavage was accompanied by the apparent
      formation of cleavage fragment(s). Stat3 cleavage fragments, reflecting multiple
      caspase cleavage sites, also were observed in vitro following STS exposure in
      DU145 cells and in HEK293T cells transfected to express Stat3 truncation mutants.
      The impact of cleavage on Stat3 transcriptional activity next was assessed and
      revealed that cleavage of fl-Stat3 was accompanied by reductions in Stat3-DNA
      binding, Stat3-driven reporter protein (luciferase) activity, and the expression
      of selected Stat3-dependent genes. Further, reduced Stat3 expression correlated
      with increased sensitivity to apoptotic stimuli. In concomitant experiments,
      reporter activity was assessed in Stat3 truncation mutant-expressing HEK293T
      cells and revealed that, under non-apoptotic conditions, expression of different
      Stat3 fragments induced differential effects on Stat3-driven luciferase activity.
      These findings demonstrate that fl-Stat3 undergoes proteolytic processing by
      caspases that reduces its expression and leads to the formation of cleavage
      fragments that may modulate Stat3 transcriptional activity.

PMID- 16636049
TI  - Screening for the preferred substrate sequence of transglutaminase using a phage
      displayed peptide library: identification of peptide substrates for TGASE 2 and
      Factor XIIIA.
AB  - Mammalian transglutaminase (TGase) catalyzes covalent cross-linking of peptide
      bound lysine residues or incorporation of primary amines to limited glutamine
      residues in substrate proteins. Using an unbiased M13 phage display random
      peptide library, we developed a screening system to elucidate primary structures
      surrounding reactive glutamine residue(s) that are preferred by TGase. Screening
      was performed by selecting phage clones expressing peptides that incorporated
      biotin-labeled primary amine by the catalytic reactions of TGase 2 and activated
      Factor XIII (Factor XIIIa). We identified several amino acid sequences that were
      preferred as glutamine donor substrates, most of which have a marked tendency for
      individual TGases: TGase 2, QxPphiD(P), QxPphi, and QxxphiDP; Factor XIIIa,
      QxxphixWP (where x and phi represent a non-conserved and a hydrophobic amino
      acid, respectively). We further confirmed that the sequences were favored for
      transamidation using modified glutathione S-transferase (GST) for recombinant
      peptide-GST fusion proteins. Most of the fusion proteins exhibited a considerable
      increase in incorporation of primary amines over that of modified GST alone.
      Furthermore, we identified the amino acid sequences that demonstrated higher
      specificity and inhibitory activity in the cross-linking reactions by TGase 2 and
      Factor XIIIa.

PMID- 16636050
TI  - Identification and functional characterization of the BAG protein family in
      Arabidopsis thaliana.
AB  - The genes that control mammalian programmed cell death are conserved across wide
      evolutionary distances. Although plant cells can undergo apoptosis-like cell
      death, plant homologs of mammalian regulators of apoptosis have, in general, not
      been found. This is in part due to the lack of primary sequence conservation
      between animal and putative plant regulators of apoptosis. Thus, alternative
      approaches beyond sequence similarities are required to find functional plant
      homologs of apoptosis regulators. Here, we present the results of using advanced
      bioinformatic tools to uncover the Arabidopsis family of BAG proteins. The
      mammalian BAG (Bcl-2-associated athanogene) proteins are a family of chaperone
      regulators that modulate a number of diverse processes ranging from proliferation
      to growth arrest and cell death. Such proteins are distinguished by a conserved
      BAG domain that directly interacts with Hsp70 and Hsc70 proteins to regulate
      their activity. Our searches of the Arabidopsis thaliana genome sequence revealed
      seven homologs of the BAG protein family. We further show that plant BAG family
      members are also multifunctional and remarkably similar to their animal
      counterparts, as they regulate apoptosis-like processes ranging from pathogen
      attack to abiotic stress and development.

PMID- 16636051
TI  - Purification and initial biochemical characterization of ATP:Cob(I)alamin
      adenosyltransferase (EutT) enzyme of Salmonella enterica.
AB  - ATP:cob(I)alamin adenosyltransferase (EutT) of Salmonella enterica was
      overproduced and enriched to approximately 70% homogeneity, and its basic kinetic
      parameters were determined. Abundant amounts of EutT protein were produced, but
      all of it remained insoluble. Soluble active EutT protein (approximately 70%
      homogeneous) was obtained after treatment with detergent. Under conditions in
      which cobalamin (Cbl) was saturating, Km(ATP) = 10 microm, kcat = 0.03 s(-1), and
      Vmax = 54.5 nm min(-1). Similarly, under conditions in which MgATP was
      saturating, Km(Cbl) = 4.1 microm, kcat = 0.06 s(-1), and Vmax = 105 nm min(-1).
      Unlike other ATP:co(I)rrinoid adenosyltransferases in the cell (i.e. CobA and
      PduO), EutT activity was > or =50-fold higher with ATP versus GTP, and EutT
      retained 80% of its activity with ADP substituted for ATP and was completely
      inactive with AMP as substrate, indicating that the enzyme requires the beta
      phosphate group of the nucleotide substrate. The data suggest that the amino
      group of adenine might play a role in nucleotide recognition and/or binding.
      Unlike the housekeeping CobA enzyme, EutT was not inhibited by inorganic
      tripolyphosphate (PPPi). Results from 31P NMR spectroscopy studies identified PPi
      and Pi as by-products of the EutT reaction. In the absence of Cbl, EutT cleaved
      ATP into adenosine and PPPi, suggesting that PPPi is broken down into PPi and Pi.
      Electron transfer protein partners for EutT were not encoded by the eut operon.
      EutT-dependent activity was detected in cell-free extracts of cobA strains
      enriched for EutT when FMN and NADH were used to reduce cob(III)alamin to
      cob(I)alamin.

PMID- 16636052
TI  - Zinc transport complexes contribute to the homeostatic maintenance of secretory
      pathway function in vertebrate cells.
AB  - Zinc transporters play important roles in a wide range of biochemical processes.
      Here we report an important function of ZnT5/ZnT6 hetero-oligomeric complexes in
      the secretory pathway. The activity of human tissue-nonspecific alkaline
      phosphatase (ALP) expressed in ZnT5(-)ZnT7(-/-) cells was significantly reduced
      compared with that expressed in wild-type cells as in the case of endogenous
      chicken tissue-nonspecific ALP activity. The inactive human tissue-nonspecific
      ALP in ZnT5(-)ZnT7(-/-) cells was degraded by proteasome-mediated degradation
      without being trafficked to the plasma membrane. ZnT5(-)ZnT7(-/-) cells showed
      exacerbation of the unfolded protein response as did the wild-type cells cultured
      under a zinc-deficient condition, revealing that both complexes play a role in
      homeostatic maintenance of secretory pathway function. Furthermore, we showed
      that expression of ZnT5 mRNA was up-regulated by the endoplasmic reticulum stress
      in various cell lines. The up-regulation of the hZnT5 transcript was mediated by
      transcription factor XBP1 through the TGACGTGG sequence in the hZnT5 promoter,
      and this sequence was highly conserved in the ZnT5 genes of mouse and chicken.
      These results suggest that zinc transport into the secretory pathway is strictly
      regulated for the homeostatic maintenance of secretory pathway function in
      vertebrate cells.

PMID- 16636053
TI  - A zinc-binding region in Vif binds Cul5 and determines cullin selection.
AB  - Human immunodeficiency virus-1 (HIV-1) Vif overcomes the anti-viral activity of
      APOBEC3G by targeting it for ubiquitination via a Cullin 5-ElonginB-ElonginC
      (Cul5-EloBC) E3 ligase. Vif associates with Cul5-EloBC through a BC-box motif
      that binds EloC, but the mechanism by which Vif selectively recruits Cul5 is
      poorly understood. Here we report that a region of Vif (residues 100-142)
      upstream of the BC-box binds selectively to Cul5 in the absence of EloC. This
      region contains a zinc coordination site HX5CX17-18CX3-5H (HCCH), with His/Cys
      residues at positions 108, 114, 133, and 139 coordinating one zinc ion. The HCCH
      zinc coordination site, which is conserved among primate lentivirus Vif proteins,
      does not correspond to any known class of zinc-binding motif. Mutations of
      His/Cys residues in the HCCH motif impair zinc coordination, Cul5 binding, and
      APOBEC3G degradation. Mutations of conserved hydrophobic residues (Ile-120, Ala
      123, and Leu-124) located between the two Cys residues in the HCCH motif disrupt
      binding of the zinc-coordinating region to Cul5 and inhibit APOBEC3G degradation.
      The Vif binding site maps to the first cullin repeat in the N terminus of Cul5.
      These data suggest that the zinc-binding region in Vif is a novel cullin
      interaction domain that mediates selective binding to Cul5. We propose that the
      HCCH zinc-binding motif facilitates Vif-Cul5 binding by playing a structural role
      in positioning hydrophobic residues for direct contact with Cul5.

PMID- 16636054
TI  - Eight amino acid residues in transmembrane segments of yeast glucose transporter
      Hxt2 are required for high affinity transport.
AB  - Hxt2 and Hxt1 are high affinity and low affinity facilitative glucose transporter
      paralogs of Saccharomyces cerevisiae, respectively, that differ at 75 amino acid
      positions in their 12 transmembrane segments (TMs). Comprehensive analysis of
      chimeras of these two proteins has previously revealed that TMs 1, 5, 7, and 8 of
      Hxt2 are required for high affinity glucose transport activity and that leucine
      201 in TM5 is the most important in this regard of the 20 amino acid residues in
      these regions that differ between Hxt2 and Hxt1. To evaluate the importance of
      the remaining residues, we systematically shuffled the amino acids at these
      positions and screened the resulting proteins for high affinity and high capacity
      glucose transport activity. In addition to leucine 201 (TM5), four residues of
      Hxt2 (leucine 59 and leucine 61 in TM1, asparagine 331 in TM7, and phenylalanine
      366 in TM8) were found to be important for such activity. Furthermore,
      phenylalanine 198 (TM5), alanine 363 (TM8), and either valine 316 (TM7) or
      alanine 368 (TM8) were found to be supportive of maximal activity. Construction
      of a homology model suggested that asparagine 331 interacts directly with the
      substrate and that the other identified residues may contribute to maintenance of
      protein conformation.

PMID- 16636055
TI  - Beta-adrenergic receptor stimulation and adenoviral overexpression of superoxide
      dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid
      reabsorption.
AB  - Hypoxia has been shown to cause lung edema and impair lung edema clearance. In
      the present study, we exposed isolated rat lungs to pO(2) = 40 mm Hg for 60 min
      or rats to 8% O(2) for up to 24 h and then measured changes in alveolar fluid
      reabsorption (AFR) and Na,K-ATPase function. Low levels of oxygen severely
      impaired AFR in both ex vivo and in vivo models. The decrease in AFR was
      associated with a decrease in Na,K-ATPase activity and protein abundance in the
      basolateral membranes from peripheral lung tissue of hypoxic rats. Beta
      adrenergic agonists restored AFR in rats exposed to 8% O(2) (from 0.02 +/- 0.07
      ml/h to 0.59 +/- 0.03 ml/h), which was associated with parallel increases in Na,K
      ATPase protein abundance in the basolateral membrane. Hypoxia is associated with
      increased production of reactive oxygen species. Therefore, we examined whether
      overexpression of SOD2, manganese superoxide dismutase, would prevent the hypoxia
      mediated decrease in AFR. Spontaneously breathing rats were infected with a
      replication-deficient human type 5 adenovirus containing cDNA for SOD2. An
      otherwise identical virus that contained no cDNA was used as a control (Adnull).
      Hypoxic Adnull rats had decreased rates of AFR (0.12 +/- 0.1 ml/h) as compared
      with hypoxic AdSOD2 and normoxic control rats (0.47 +/- 0.04 ml/h and 0.49 +/-
      0.02 ml/h, respectively), with parallel changes in Na,K-ATPase.

PMID- 16636056
TI  - Dot1a-AF9 complex mediates histone H3 Lys-79 hypermethylation and repression of
      ENaCalpha in an aldosterone-sensitive manner.
AB  - Aldosterone is a major regulator of epithelial Na(+) absorption and acts in large
      part through induction of the epithelial Na(+) channel (ENaC) gene in the renal
      collecting duct. We previously identified Dot1a as an aldosterone early repressed
      gene and a repressor of ENaCalpha transcription through mediating histone H3 Lys
      79 methylation associated with the ENaCalpha promoter. Here, we report a novel
      aldosterone-signaling network involving AF9, Dot1a, and ENaCalpha. AF9 and Dot1a
      interact in vitro and in vivo as evidenced in multiple assays and colocalize in
      the nuclei of mIMCD3 renal collecting duct cells. Overexpression of AF9 results
      in hypermethylation of histone H3 Lys-79 at the endogenous ENaCalpha promoter at
      most, but not all subregions examined, repression of endogenous ENaCalpha mRNA
      expression and acts synergistically with Dot1a to inhibit ENaCalpha promoter
      luciferase constructs. In contrast, RNA interference-mediated knockdown of AF9
      causes the opposite effects. Chromatin immunoprecipitation assays reveal that
      overexpressed FLAG-AF9, endogenous AF9, and Dot1a are each associated with the
      ENaCalpha promoter. Aldosterone negatively regulates AF9 expression at both mRNA
      and protein levels. Thus, Dot1a-AF9 modulates histone H3 Lys-79 methylation at
      the ENaCalpha promoter and represses ENaCalpha transcription in an aldosterone
      sensitive manner. This mechanism appears to be more broadly applicable to other
      aldosterone-regulated genes because overexpression of AF9 alone or in combination
      with Dot1a inhibited mRNA levels of three other known aldosterone-inducible genes
      in mIMCD3 cells.

PMID- 16636057
TI  - Phosphoinositide 3-kinase in nitric oxide synthesis in macrophage: critical
      dimerization of inducible nitric-oxide synthase.
AB  - Phosphoinositide 3-kinase (PI3K) has important functions in various biological
      systems, including immune response. Although the role of PI3K in signaling by
      antigen-specific receptors of the adaptive immune system has been extensively
      studied, less is known about the function of PI3K in innate immunity. In the
      present study, we demonstrate that macrophages deficient for PI3K (p85alpha
      regulatory subunit) are impaired in nitric oxide (NO) production upon
      lipopolysaccharide and interferon-gamma stimulation and thus vulnerable for
      intracellular bacterial infection such as Chlamydophila pneumoniae. Although
      expression of inducible nitric-oxide synthase (iNOS) is induced normally in PI3K
      deficient macrophages, dimer formation of iNOS protein is significantly impaired.
      The amount of intracellular tetrahydrobiopterin, a critical stabilizing cofactor
      for iNOS dimerization, is decreased in the absence of PI3K. In addition,
      induction of GTP cyclohydrolase 1, a rate-limiting enzyme for biosynthesis of
      tetrahydrobiopterin, is greatly reduced. Our current results demonstrate a
      critical role of class IA type PI3K in the bactericidal activity of macrophages
      by regulating their NO production through GTP cyclohydrolase 1 induction.

PMID- 16636058
TI  - Contributions of phenylalanine 335 to ligand recognition by human surfactant
      protein D: ring interactions with SP-D ligands.
AB  - Surfactant protein D (SP-D) is an innate immune effector that contributes to
      antimicrobial host defense and immune regulation. Interactions of SP-D with
      microorganisms and organic antigens involve binding of glycoconjugates to the C
      type lectin carbohydrate recognition domain (CRD). A trimeric fusion protein
      encoding the human neck+CRD bound to the aromatic glycoside p-nitrophenyl-alpha-D
      maltoside with nearly a log-fold higher affinity than maltose, the prototypical
      competitor. Maltotriose, which has the same linkage pattern as the maltoside,
      bound with intermediate affinity. Site-directed substitution of leucine for
      phenylalanine 335 (Phe-335) decreased affinities for the maltoside and
      maltotriose without significantly altering the affinity for maltose or glucose,
      and substitution of tyrosine or tryptophan for leucine restored preferential
      binding to maltotriose and the maltoside. A mutant with alanine at this position
      failed to bind to mannan or maltose-substituted solid supports. Crystallographic
      analysis of the human neck+CRD complexed with maltotriose or p-nitrophenyl
      maltoside showed stacking of the terminal glucose or nitrophenyl ring with the
      aromatic ring of Phe-335. Our studies indicate that Phe-335, which is
      evolutionarily conserved in all known SP-Ds, plays important, if not critical,
      roles in SP-D function.

PMID- 16636059
TI  - Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair
      neuronal plasticity and cognitive function.
AB  - A subtle but chronic alteration in metabolic balance between amyloid-beta peptide
      (Abeta) anabolic and catabolic activities is thought to cause Abeta accumulation,
      leading to a decade-long pathological cascade of Alzheimer disease. However, it
      is still unclear whether a reduction of the catabolic activity of Abeta in the
      brain causes neuronal dysfunction in vivo. In the present study, to clarify a
      possible connection between a reduction in neprilysin activity and impairment of
      synaptic and cognitive functions, we cross-bred amyloid precursor protein (APP)
      transgenic mice (APP23) with neprilysin-deficient mice and biochemically and
      immunoelectron-microscopically analyzed Abeta accumulation in the brain. We also
      examined hippocampal synaptic plasticity using an in vivo recording technique and
      cognitive function using a battery of learning and memory behavior tests,
      including Y-maze, novel-object recognition, Morris water maze, and contextual
      fear conditioning tests at the age of 13-16 weeks. We present direct experimental
      evidence that reduced activity of neprilysin, the major Abeta-degrading enzyme,
      in the brain elevates oligomeric forms of Abeta at the synapses and leads to
      impaired hippocampal synaptic plasticity and cognitive function before the
      appearance of amyloid plaque load. Thus, reduced neprilysin activity appears to
      be a causative event that is at least partly responsible for the memory
      associated symptoms of Alzheimer disease. This supports the idea that a strategy
      to reduce Abeta oligomers in the brain by up-regulating neprilysin activity would
      contribute to alleviation of these symptoms.

PMID- 16636060
TI  - Genetic requirements for growth of Escherichia coli K12 on methyl-alpha-D
      glucopyranoside and the five alpha-D-glucosyl-D-fructose isomers of sucrose.
AB  - Strains of Escherichia coli K12, including MG-1655, accumulate methyl-alpha-D
      glucopyranoside via the phosphoenolpyruvate-dependent glucose:phosphotransferase
      system (IICB(Glc)/IIA(Glc)). High concentrations of intracellular methyl-alpha-D
      glucopyranoside 6-phosphate are toxic, and cell growth is prevented. However,
      transformation of E. coli MG-1655 with a plasmid (pAP1) encoding the gene aglB
      from Klebsiella pneumoniae resulted in excellent growth of the transformant MG
      1655 (pAP1) on the glucose analog. AglB is an unusual NAD+/Mn2+-dependent phospho
      alpha-glucosidase that promotes growth of MG-1655 (pAP1) by catalyzing the in
      vivo hydrolysis of methyl-alpha-D-glucopyranoside 6-phosphate to yield glucose 6
      phosphate and methanol. When transformed with plasmid pAP2 encoding the K.
      pneumoniae genes aglB and aglA (an alpha-glucoside-specific transporter AglA
      (IICB(Agl))), strain MG-1655 (pAP2) metabolized a variety of other alpha-linked
      glucosides, including maltitol, isomaltose, and the following five isomers of
      sucrose: trehalulose alpha(1-->1), turanose alpha(1-->3), maltulose alpha(1-->4),
      leucrose alpha(1-->5), and palatinose alpha(1-->6). Remarkably, MG-1655 (pAP2)
      failed to metabolize sucrose alpha(1-->2). The E. coli K12 strain ZSC112L
      (ptsG::cat manXYZ nagE glk lac) can neither grow on glucose nor transport methyl
      alpha-D-glucopyranoside. However, when transformed with pTSGH11 (encoding ptsG)
      or pAP2, this organism provided membranes that contained either the PtsG or AglA
      transporters, respectively. In vitro complementation of transporter-specific
      membranes with purified general phosphotransferase components showed that
      although PtsG and AglA recognized glucose and methyl-alpha-D-glucopyranoside,
      only AglA accepted other alpha-D-glucosides as substrates. Complementation
      experiments also revealed that IIA(Glc) was required for functional activity of
      both PtsG and AglA transporters. We conclude that AglA, AglB, and IIA(Glc) are
      necessary and sufficient for growth of E. coli K12 on methyl-alpha-D-glucoside
      and related alpha-D-glucopyranosides.

PMID- 16636061
TI  - For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver
      protects whereas mouse CYP1A1 and CYP1B1 are inconsequential.
AB  - Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces cleft palate and
      hydronephrosis in mice, when exposed in utero; these effects are mediated by the
      aryl hydrocarbon receptor. The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated
      by the aryl hydrocarbon receptor. To elucidate their roles in dioxin-induced
      teratogenesis, we compared Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1b1(-/-) knock-out
      mice with Cyp1(+/+) wild-type mice. Dioxin was administered (25 microg/kg,
      gavage) on gestational day 10, and embryos were examined on gestational day 18.
      The incidence of cleft palate and hydronephrosis was not significantly different
      in fetuses from Cyp1a1(-/-), Cyp1b1(-/-), and Cyp1(+/+) wild-type mice. To
      fetuses carried by Cyp1a2(-/-) dams, however, this dose of dioxin was lethal;
      this effect was absolutely dependent on the maternal Cyp1a2 genotype and
      independent of the embryonic Cyp1a2 genotype. Dioxin levels were highest in
      adipose tissue, mammary gland, and circulating blood of Cyp1a2(-/-) mothers,
      compared with that in the Cyp1(+/+) mothers, who showed highest dioxin levels in
      liver. More dioxin reached the embryos from Cyp1a2(-/-) dams, compared with that
      from Cyp1(+/+) dams. Fetuses from Cyp1a2(-/-) dams exhibited a approximately 6
      fold increased sensitivity to cleft palate, hydronephrosis, and lethality. Using
      the humanized hCYP1A1_1A2 transgenic mouse (expressing the human CYP1A1 and
      CYP1A2 genes in the absence of mouse Cyp1a2 gene), the teratogenic effects of
      dioxin reverted to the wild-type phenotype. These data indicate that maternal
      mouse hepatic CYP1A2, by sequestering dioxin and thus altering the
      pharmacokinetics, protects the embryos from toxicity and birth defects;
      substitution of the human CYP1A2 trans-gene provides the same protection. In
      contrast, neither CYP1A1 nor CYP1B1 appears to play a role in dioxin-mediated
      teratogenesis.

PMID- 16636062
TI  - Differential recognition of citrate and a metal-citrate complex by the bacterial
      chemoreceptor Tcp.
AB  - The chemoreceptor Tcp of Salmonella enterica serovar Typhimurium can sense
      citrate and a metal-citrate complex as distinct attractants. In this study, we
      tried to investigate the molecular mechanism of this discrimination. That citrate
      binds directly to Tcp was verified by the site-specific thiol modification assays
      using membrane fractions prepared from Escherichia coli cells expressing the
      mutant Tcp receptors in which single Cys residues were introduced at positions in
      the putative ligand-binding pocket. To determine the region responsible for the
      ligand discrimination, we screened for mutations defective in taxis to magnesium
      in the presence of citrate. All of the isolated mutants from random mutagenesis
      with hydroxylamine were defective in both citrate and metal-citrate sensing, and
      the mutated residues are located in or near the alpha1-alpha2 and alpha3-alpha4
      loops within the periplasmic domain. Further analyses with site-directed
      replacements around these regions demonstrated that the residue Asn(67), which is
      presumed to lie at the subunit interface of the Tcp homodimer, plays a critical
      role in the recognition of the metal-citrate complex but not that of citrate.
      Various amino acids at this position differentially affect the citrate and metal
      citrate sensing abilities. Thus, for the first time, the abilities to sense the
      two attractants were genetically dissected. Based on the results obtained in this
      study, we propose models in which the discrimination of the metal-citrate complex
      from citrate involves cooperative interaction at Asn(67) and allosteric
      switching.

PMID- 16636063
TI  - Gadd45a and Gadd45b protect hematopoietic cells from UV-induced apoptosis via
      distinct signaling pathways, including p38 activation and JNK inhibition.
AB  - Gadd45a, Gadd45b, and Gadd45g (Gadd45/MyD118/CR6) are genes that are rapidly
      induced by genotoxic stress and have been implicated in genotoxic stress-induced
      responses, notably in apoptosis. Recently, using myeloid-enriched bone marrow
      (BM) cells obtained from wild-type (WT), Gadd45a-deficient, and Gadd45b-deficient
      mice, we have shown that in hematopoietic cells Gadd45a and Gadd45b play a
      survival function to protect hematopoietic cells from DNA-damaging agents,
      including ultra violet (UV)-induced apoptosis. The present study was undertaken
      to decipher the molecular paths that mediate the survival functions of Gadd45a
      and Gadd45b against genotoxic stress induced by UV radiation. It is shown that in
      hematopoietic cells exposed to UV radiation Gaddd45a and Gadd45b cooperate to
      promote cell survival via two distinct signaling pathways involving activation of
      the GADD45a-p38-NF-kappaB-mediated survival pathway and GADD45b-mediated
      inhibition of the stress response MKK4-JNK pathway.

PMID- 16636064
TI  - The estrogen-responsive B box protein is a novel regulator of the retinoid
      signal.
AB  - Retinoic acid (RA) induces growth arrest, cell death, and differentiation in many
      human cancer cells in vitro and has entered routine clinical use for the
      treatment of several human cancer types. One mechanism by which cancer cells
      evade retinoid-induced effects is through repression of retinoic acid receptor
      beta (RARbeta) gene transcription. The RA response element beta (betaRARE) is the
      essential DNA sequence required for retinoid-induced RARbeta transcription. Here
      we show that the estrogen-responsive B box protein (EBBP), a member of the RING-B
      box-coiled-coil protein family, is a betaRARE-binding protein. EBBP undergoes
      serine threonine phosphorylation and enhanced protein stability after RA
      treatment. Following RA treatment, we also observed increased nuclear EBBP levels
      in aggregates with the promyelocytic leukemia protein at promyelocytic leukemia
      nuclear bodies. EBBP enhanced RA-responsive RARbeta transcription in RA-sensitive
      and -resistant cancer cells, which were resistant to both a histone deacetylase
      inhibitor and a demethylating agent. EBBP-specific small interfering RNA reduced
      basal and RA-induced RARbeta expression. EBBP increased betaRARE-transactivating
      function through its coiled-coil domain. Taken together, our work suggests that
      EBBP may have a pivotal role in the retinoid anti-cancer signal.

PMID- 16636065
TI  - A new motif necessary and sufficient for stable localization of the delta2
      glutamate receptors at postsynaptic spines.
AB  - The number of each subclass of ionotropic glutamate receptors (iGluRs) at the
      spines is differentially regulated either constitutively or in a neuronal
      activity-dependent manner. The delta2 glutamate receptor (GluRdelta2) is
      abundantly expressed at the spines of Purkinje cell dendrites and controls
      synaptic plasticity in the cerebellum. To obtain clues to the trafficking
      mechanism of the iGluRs, we expressed wild-type or mutant GluRdelta2 in cultured
      hippocampal and Purkinje neurons and analyzed their intracellular localization
      using immunocytochemical techniques. Quantitative analysis revealed that deletion
      of the 20 amino acids at the center of the C terminus (region E) significantly
      reduced the amount of GluRdelta2 protein at the spines in both types of neurons.
      This effect was partially antagonized by the inhibition of endocytosis by high
      dose sucrose treatment or coexpression of dominant negative dynamin. In addition,
      mutant GluRdelta2 lacking the E region (GluRdelta2DeltaE), but not wild-type
      GluRdelta2, was found to colocalize with the endosomal markers Rab4 and Rab7.
      Moreover, the antibody-feeding assay revealed that GluRdelta2DeltaE was
      internalized more rapidly than GluRdelta2wt. These results indicate that the E
      region (more specifically, a 12-amino-acid-long segment of the E2 region) is
      necessary for rendering GluRdelta2 resistant to endocytosis from the cell surface
      at the spines. Furthermore, insertion of the E2 region alone into the C terminus
      of the GluR1 subtype of iGluRs was sufficient to increase the amount of GluR1
      proteins in the spines. Therefore, we propose that the E2 region of GluRdelta2 is
      necessary, and also sufficient, to inhibit endocytosis of the receptor from
      postsynaptic membranes.

PMID- 16636066
TI  - The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2
      domains.
AB  - Nck proteins are essential Src homology (SH) 2 and SH3 domain-bearing adapters
      that modulate actin cytoskeleton dynamics by linking proline-rich effector
      molecules to tyrosine kinases or phosphorylated signaling intermediates. Two
      mammalian pathogens, enteropathogenic Escherichia coli and vaccinia virus,
      exploit Nck as part of their infection strategy. Conflicting data indicate
      potential differences in the recognition specificities of the SH2 domains of the
      isoproteins Nck1 (Nckalpha) and Nck2 (Nckbeta and Grb4). We have characterized
      the binding specificities of both SH2 domains and find them to be essentially
      indistinguishable. Crystal structures of both domains in complex with
      phosphopeptides derived from the enteropathogenic E. coli protein Tir concur in
      identifying highly conserved, specific recognition of the phosphopeptide.
      Differential peptide recognition can therefore not account for the preference of
      either Nck in particular signaling pathways. Binding studies using sequentially
      mutated, high affinity phosphopeptides establish the sequence variability
      tolerated in peptide recognition. Based on this binding motif, we identify
      potential new binding partners of Nck1 and Nck2 and confirm this experimentally
      for the Arf-GAP GIT1.

PMID- 16636067
TI  - Nox1-dependent reactive oxygen generation is regulated by Rac1.
AB  - Rac1 has been implicated in the generation of reactive oxygen species (ROS) in
      several cell types, but the enzymatic origin of the ROS has not been proven. The
      present studies demonstrate that Nox1, a homolog of the phagocyte NADPH-oxidase
      component gp91(phox), is activated by Rac1. When Nox1 is co-expressed along with
      its regulatory subunits NOXO1 and NOXA1, significant ROS generation is seen.
      Herein, co-expression of constitutively active Rac1(G12V), but not wild-type
      Rac1, resulted in marked further stimulation of activity. Decreased Rac1
      expression using small interfering RNA reduced Nox1-dependent ROS. CDC42(G12V)
      failed to increase activity, and small interfering RNA directed against CDC42
      failed to decrease activity, pointing to specificity for Rac. TPR domain mutants
      of NOXA1 that interfere with Rac1 binding were ineffective in supporting Nox1
      dependent ROS generation. Immunoprecipitation experiments demonstrated a complex
      containing Rac1(G12V), NOXO1, NOXA1, and Nox1. CDC42(G12V) could not substitute
      for Rac1(G12V) in such a complex. Nox1 formed a complex with Rac1(G12V) that was
      independent of NOXA1 and NOXO1, consistent with direct binding of Rac1(G12V) to
      Nox1. Rac1(G12V) interaction with NOXA1 was enhanced by Nox1 and NOXO1,
      suggesting cooperative binding. A model is presented comparing activation by
      regulatory subunits of Nox1 versus gp91(phox) (Nox2) in which Rac1 activation
      provides a major trigger that acutely activates Nox1-dependent ROS generation.

PMID- 16636068
TI  - Metastatic potential of mouse Lewis lung cancer cells is regulated via
      ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid
      rafts.
AB  - To analyze mechanisms for cancer metastasis, we established high metastatic
      sublines from mouse Lewis lung cancer (P29) by repeated injection. Sublines
      established from the two subclones H7 and C4 commonly exhibited increased
      proliferation and invasion activity and reduced expression of ganglioside GM1,
      although they showed different preferences in their target organs of metastasis.
      The high metastatic sublines secreted higher levels of activated matrix
      metalloprotease (MMP)-9 as well as pro-MMP-9 in the culture medium than the
      parent lines. Furthermore, they contained MMP-9 at the glycolipid-enriched
      microdomain (GEM)/rafts fractionated by the sucrose density gradient
      ultracentrifugation of Triton X-100 extracts, whereas the parent cells showed
      faint bands at the fraction. When high metastatic sublines were treated with
      methyl-beta-cyclodextrin, their invasion activities were dramatically suppressed,
      and the MMP-9 secretion was also suppressed. All these results indicated that
      GEM/rafts play crucial roles in the increased invasion and high metastatic
      potential. To clarify the implication of reduced GM1 expression, low GM1
      expressing cell lines were established using an RNA interference-expression
      vector of the GM1 synthase. Low GM1-expressing cell lines showed increased
      proliferation and invasion, enrichment in the GEM/rafts, and increased secretion
      of MMP-9. Among adhesion molecules, only integrin beta1 was detected in GEM/rafts
      with stronger intensity in high metastatic lines and low GM1-expressing cells.
      Taken together, integrins seemed to be enriched in the GEM/rafts by reduced GM1
      levels, and subsequently MMP-9 was recruited to the GEM/rafts, resulting in its
      efficient secretion and activation, and eventually in the increased invasion and
      metastatic potentials.

PMID- 16636069
TI  - Recycling endosomes.

PMID- 16636070
TI  - Dynamin as a mover and pincher during cell migration and invasion.
AB  - The large GTPase dynamin, long known for its role in endocytosis, has most
      recently been implicated as a facilitator of cell migration and invasion. Recent
      observations link dynamin to the cycle of membrane expansion and retraction
      essential for cell motility. Its role in actin polymerization, membrane
      deformation and vesiculation, and focal adhesion dynamics are all important for
      this process, and the new findings provide exciting directions for studies of
      this ubiquitous and diverse protein family.

PMID- 16636071
TI  - Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening
      response to fluid flow.
AB  - Cells in vivo are constantly subjected to mechanical shear stresses that play
      important regulatory roles in various physiological and pathological processes.
      Cytoskeletal reorganizations that occur in response to shear flow have been
      studied extensively, but whether the cytoplasm of an adherent cell adapts its
      mechanical properties to respond to shear is largely unknown. Here we develop a
      new method where fluorescent nanoparticles are ballistically injected into the
      cells to probe, with high resolution, possible local viscoelastic changes in the
      cytoplasm of individual cells subjected to fluid flow. This new assay, ballistic
      intracellular nanorheology (BIN), reveals that shear flow induces a dramatic
      sustained 25-fold increase in cytoplasmic viscosity in serum-starved Swiss 3T3
      fibroblasts. By contrast, cells stimulated with the actin contractile agonist LPA
      show highly transient stiffening of much lower amplitude, despite the formation
      of similar cytoskeletal structures. Shear-induced cytoplasmic stiffening is
      attenuated by inhibiting actomyosin interactions and is entirely eliminated by
      specific Rho-kinase (ROCK) inhibition. Together, these results show that
      biochemical and biophysical stimuli may elicit the formation of qualitatively
      similar cytoskeleton structures (i.e. stress fibers and focal adhesions), but
      induces quantitatively different micromechanical responses. Our results suggest
      that when an adherent cell is subjected to shear stresses, its first order of
      action is to prevent detachment from its substratum by greatly stiffening its
      cytoplasm through enhanced actin assembly and Rho-kinase mediated contractility.

PMID- 16636072
TI  - Abnormal sterols in cholesterol-deficiency diseases cause secretory granule
      malformation and decreased membrane curvature.
AB  - Cholesterol is an abundant lipid in eukaryotic membranes, implicated in numerous
      structural and functional capacities. Here, we have investigated the mechanism by
      which cholesterol affects secretory granule biogenesis in vivo using Dhcr7(-/-)
      and Sc5d(-/-) mouse models of the human diseases, Smith-Lemli-Opitz syndrome
      (SLOS) and lathosterolosis. These homozygous-recessive multiple-malformation
      disorders are characterized by the functional absence of one of the last two
      enzymes in the cholesterol biosynthetic pathway, resulting in the accumulation of
      precursors. Cholesterol-deficient mice exhibit a significant decrease in the
      numbers of secretory granules in the pancreas, pituitary and adrenal glands.
      Moreover, there was an increase in morphologically aberrant granules in the
      exocrine pancreas of Dhcr7(-/-) acinar cells. Regulated secretory pathway
      function was also severely diminished in these cells, but could be restored with
      exogenous cholesterol. Sterol precursors incorporated in artificial membranes
      resulted in decreased bending rigidity and intrinsic curvature compared with
      cholesterol, thus providing a cholesterol-mediated mechanism for normal granule
      budding, and an explanation for granule malformation in SLOS and lathosterolosis.

PMID- 16636073
TI  - Interactions of primary fibroblasts and keratinocytes with extracellular matrix
      proteins: contribution of alpha2beta1 integrin.
AB  - The alpha2beta1 integrin is a collagen-binding protein with very high affinity
      for collagen I. It also binds several other collagens and laminins and it is
      expressed by many cells, including keratinocytes and fibroblasts in the skin. In
      the past, alpha2beta1 integrin was suggested to be responsible for cell
      attachment, spreading and migration on monomeric collagen I and contraction of
      three-dimensional collagen lattices. In view of these functions, normal
      development and fertility in integrin alpha2-deficient mice, which we generated
      by targeting the integrin alpha2 gene, came as a surprise. This suggested the
      existence of compensatory mechanisms that we investigate here using primary
      fibroblasts and keratinocytes isolated from wild-type and alpha2-deficient mice,
      antibodies blocking integrin function and downregulation of integrin alpha2
      expression. The results show that the alpha2beta1 integrin is absolutely required
      for keratinocyte adhesion to collagens whereas for fibroblasts other collagen
      binding integrins partially back-up the lack of alpha2beta1 in simple adhesion to
      collagen monomers. A prominent requirement for alpha2beta1 integrins became
      apparent when fibroblasts executed mechanical tasks of high complexity in three
      dimensional surroundings, such as contracting free-floating collagen gels and
      developing isometric forces in tethered lattices. The deficits observed for
      alpha2-deficient fibroblasts appeared to be linked to alterations in the
      distribution of force-bearing focal adhesions and deregulation of Rho-GTPase
      activation.

PMID- 16636074
TI  - Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts.
AB  - During bone development, osteoblast differentiation requires remodeling of the
      extracellular matrix. Although underlying mechanisms have not been elucidated,
      evidence points to the participation of the nitric oxide (NO) and cyclic
      guanosine 3',5'-monophosphate (cGMP) system. Here, we detected increased matrix
      metalloproteinase (MMP)-13 mRNA, protein and activity, as well as increased
      inducible NO synthase (iNOS) and NO production during the differentiation of
      MC3T3-E1 osteoblasts. Transcriptional activity of the MMP-13 promoter was
      augmented by NO, 8-bromo-cGMP (8-Br-cGMP), and by a dominant-positive form of
      protein kinase G (PKG1-alpha). The stimulatory effect on the MMP-13 promoter was
      partially inhibited by mutation of the osteoblast-specific element 2 (OSE-2)
      binding site. Core binding factor-1 (Cbfa-1) expression peaked at 7 days of
      differentiation, and was phosphorylated by PKG in vitro. Cbfa-1 was localized to
      cell nuclei, and its translocation was inhibited by the iNOS inhibitor 1400W.
      Immunohistological examination revealed that MMP-13 and Cbfa-1 expression levels
      are both reduced in 17-day-old embryos of iNOS-deficient mice. Silencing of Cbfa
      1 mRNA blocked MMP-13 expression without interfering with endogenous NO
      production, confirming its role in NO-induced MMP-13 expression by MC3T3-E1
      cells. The results described here suggest a mechanism by which NO regulates
      osteogenesis.

PMID- 16636075
TI  - Mechanics of neutrophil phagocytosis: experiments and quantitative models.
AB  - To quantitatively characterize the mechanical processes that drive phagocytosis,
      we observed the FcgammaR-driven engulfment of antibody-coated beads of diameters
      3 mum to 11 mum by initially spherical neutrophils. In particular, the time
      course of cell morphology, of bead motion and of cortical tension were
      determined. Here, we introduce a number of mechanistic models for phagocytosis
      and test their validity by comparing the experimental data with finite element
      computations for multiple bead sizes. We find that the optimal models involve two
      key mechanical interactions: a repulsion or pressure between cytoskeleton and
      free membrane that drives protrusion, and an attraction between cytoskeleton and
      membrane newly adherent to the bead that flattens the cell into a thin lamella.
      Other models such as cytoskeletal expansion or swelling appear to be ruled out as
      main drivers of phagocytosis because of the characteristics of bead motion during
      engulfment. We finally show that the protrusive force necessary for the
      engulfment of large beads points towards storage of strain energy in the
      cytoskeleton over a large distance from the leading edge ( approximately 0.5
      microm), and that the flattening force can plausibly be generated by the known
      concentrations of unconventional myosins at the leading edge.

PMID- 16636076
TI  - Spatiotemporal dynamics of actin-rich adhesion microdomains: influence of
      substrate flexibility.
AB  - In this study we analyse the formation and dynamics of specific actin-rich
      structures called podosomes. Podosomes are very dynamic punctual adhesion sites
      tightly linked to the actin cytoskeleton. Mechanical properties of substrates are
      emerging as important physical modulators of anchorage-dependent processes
      involved in the cellular response. We investigate the influence of substrate
      flexibility on the dynamic properties of podosomes. We used mouse NIH-3T3
      fibroblasts, transfected with GFP-actin and cultured on polyacrylamide collagen
      coated substrates of varying stiffness. Static and dynamic features of cell
      morphologies associated with an optical flow analysis of the dynamics of
      podosomes revealed that: (1) they have constant structural properties, i.e. their
      shape factor and width do not change with the substrate flexibility; (2) the
      lifespan of podosomes and mean minimum distance between them depend on the
      substrate flexibility; (3) there is a variation in the displacement speed of the
      rosette of podosomes. Moreover, the rosettes sometimes appear as periodically
      emergent F-actin structures, which suggests that a two-level self-organisation
      process may drive first, the formation of clusters of podosomes and second, the
      organisation of these clusters into oscillating rings. Such dynamic features give
      new perspectives regarding the potential function of podosomes as mechanosensory
      structures.

PMID- 16636077
TI  - Differential action of steroid hormones on human endothelium.
AB  - The action of glucocorticoids on vascular permeability is well established.
      However, little is known about the action of mineralocorticoids on the structure
      and function of blood vessels. As endothelial cells are targets for both
      glucocorticoids and mineralocorticoids, we exposed human umbilical vein
      endothelial cells to both types of steroids. Aldosterone (mineralocorticoid) and
      dexamethasone (glucocorticoid) were applied for 3 days in culture before
      measurements of transendothelial ion and macromolecule permeability, apical cell
      surface and cell stiffness were taken. Transendothelial ion permeability was
      measured with electrical cell impedance sensing, macromolecule permeability with
      fluorescence-labeled dextran and apical cell membrane surface by three
      dimensional AFM imaging. Cell stiffness was measured using the AFM scanning tip
      as a mechanical nanosensor. We found that aldosterone increased both apical cell
      surface and apical cell stiffness significantly, while transendothelial
      permeability remained unaffected. By contrast, dexamethasone significantly
      decreased ion and macromolecule permeability, while apical cell surface and cell
      stiffness did not change. Specific receptor antagonists for dexamethasone (RU486)
      and aldosterone (spironolactone) prevented the observed responses. We conclude
      that glucocorticoids strengthen cell-to-cell contacts (;peripheral action'),
      whereas mineralocorticoids enlarge and stiffen cells (;central action'). This
      could explain the dexamethasone-mediated retention of fluid in the vascular
      system, and endothelial dysfunction in states of hyperaldosteronism.

PMID- 16636078
TI  - Methylation regulates the intracellular protein-protein and protein-RNA
      interactions of FMRP.
AB  - FMRP, the fragile X mental retardation protein, is an RNA-binding protein that
      interacts with approximately 4% of fetal brain mRNA. We have recently shown that
      a methyltransferase (MT) co-translationally methylates FMRP in vitro and that
      methylation modulates the ability of FMRP to bind mRNA. Here, we recapitulate
      these in vitro data in vivo, demonstrating that methylation of FMRP affects its
      ability to bind to FXR1P and regulate the translation of FMRP target mRNAs.
      Additionally, using double-label fluorescence confocal microscopy, we identified
      a subpopulation of FMRP-containing small cytoplasmic granules that are
      distinguishable from larger stress granules. Using the oxidative-stress induced
      accumulation of abortive pre-initiation complexes as a measure of the association
      of FMRP with translational components, we have demonstrated that FMRP associates
      with ribosomes during initiation and, more importantly, that methylation
      regulates this process by influencing the ratio of FMRP-homodimer-containing
      mRNPs to FMRP-FXR1P-heterodimer-containing mRNPs. These data suggest a vital role
      for methylation in normal FMRP functioning.

PMID- 16636079
TI  - Phosphorylation on Ser5 increases the F-actin-binding activity of L-plastin and
      promotes its targeting to sites of actin assembly in cells.
AB  - L-plastin, a malignant transformation-associated protein, is a member of a large
      family of actin filament cross-linkers. Here, we analysed how phosphorylation of
      L-plastin on Ser5 of the headpiece domain regulates its intracellular
      distribution and its interaction with F-actin in transfected cells and in in
      vitro assays. Phosphorylated wild-type L-plastin localised to the actin
      cytoskeleton in transfected Vero cells. Ser5Ala substitution reduced the capacity
      of L-plastin to localise with peripheral actin-rich membrane protrusions.
      Conversely, a Ser5Glu variant mimicking a constitutively phosphorylated state,
      accumulated in actin-rich regions and promoted the formation of F-actin
      microspikes in two cell lines. Similar to phosphorylated wild-type L-plastin,
      this variant remained associated with cellular F-actin in detergent-treated
      cells, whereas the Ser5Ala variant was almost completely extracted. When compared
      with non-phosphorylated protein, phosphorylated L-plastin and the Ser5Glu variant
      bound F-actin more efficiently in an in vitro assay. Importantly, expression of L
      plastin elicited collagen invasion in HEK293T cells, in a manner dependent on
      Ser5 phosphorylation. Based on our findings, we propose that conversely to other
      calponin homology (CH)-domain family members, phosphorylation of L-plastin
      switches the protein from a low-activity to a high-activity state. Phosphorylated
      L-plastin might act as an integrator of signals controlling the assembly of the
      actin cytoskeleton and cell motility in a 3D-space.

PMID- 16636080
TI  - Five Arabidopsis peroxin 11 homologs individually promote peroxisome elongation,
      duplication or aggregation.
AB  - Pex11 homologs and dynamin-related proteins uniquely regulate peroxisome division
      (cell-cycle-dependent duplication) and proliferation (cell-cycle-independent
      multiplication). Arabidopsis plants possess five Pex11 homologs designated in
      this study as AtPex11a, -b, -c, -d and -e. Transcripts for four isoforms were
      found in Arabidopsis plant parts and in cells in suspension culture; by contrast,
      AtPex11a transcripts were found only in developing siliques. Within 2.5 hours
      after biolistic bombardments, myc-tagged or GFP-tagged AtPex11 a, -b, -c, -d and 
      e individually sorted from the cytosol directly to peroxisomes; none trafficked
      indirectly through the endoplasmic reticulum. Both termini of myc-tagged AtPex11
      b, -c, -d and -e faced the cytosol, whereas the N- and C-termini of myc-AtPex11a
      faced the cytosol and matrix, respectively. In AtPex11a- or AtPex11e-transformed
      cells, peroxisomes doubled in number. Those peroxisomes bearing myc-AtPex11a, but
      not myc-AtPex11e, elongated prior to duplication. In cells transformed with
      AtPex11c or AtPex11d, peroxisomes elongated without subsequent fission. In
      AtPex11b-transformed cells, peroxisomes were aggregated and rounded. A C-terminal
      dilysine motif, present in AtPex11c, -d and -e, was not necessary for AtPex11d
      induced peroxisome elongation. However, deletion of the motif from myc-AtPex11e
      led to peroxisome elongation and fission, indicating that the motif in this
      isoform promotes fission without elongation. In summary, all five overexpressed
      AtPex11 isoforms sort directly to peroxisomal membranes where they individually
      promote duplication (AtPex11a, -e), aggregation (AtPex11b), or elongation without
      fission (AtPex11c, -d).

PMID- 16636081
TI  - Lipid-covered drug particles: combined action of dioctadecyldimethylammonium
      bromide and amphotericin B or miconazole.
AB  - OBJECTIVES: Coverage of antifungal drug particles (miconazole and amphotericin B)
      with cationic lipid and evaluation of a synergistic action between lipid and
      drug. METHODS: Miconazole and amphotericin B were mixed with cationic bilayer
      fragments (BF) of dioctadecyldimethylammonium bromide (DODAB) at extreme drug to
      lipid molar proportions (P). Light scattering for particle sizing and zeta
      potential analysis evaluated effects of cationic lipid on drug particle size and
      charge. Colony counts evaluated viability of Candida spp. and Cryptococcus
      neoformans over a range of P. RESULTS: BF loading capacity for monomeric
      amphotericin B is 0.1 mM amphotericin B at 2 mM DODAB (P = 1:20). Above this low
      P, amphotericin B aggregates in the dispersion. At high P, addition of chaotropic
      K2HPO4 (0.2-2 mM) converts miconazole or amphotericin B aggregates into
      negatively charged particles with affinity for cationic lipid, which then
      surrounds each drug particle with a cationic layer. The combined in vitro action
      of lipid-covered drug particles against Candida and C. neoformans depends on P
      and interaction time. DODAB by itself kills C. neoformans and Candida at 2 and 2
      to > 250 mg/L minimal fungicidal concentration (MFC). In combination, over the
      first hour, fungicidal activity is due to DODAB with lipid capsules retarding
      drug action. At 48 h interaction time and 10(4) cfu/mL, MFC (mg/L) against
      Candida albicans is reduced from 4 to 1 amphotericin B (at 2 DODAB), and from 8
      to 1 miconazole (at 1 DODAB). CONCLUSIONS: DODAB may be a suitable candidate for
      use in combination with miconazole for antifungal therapy.

PMID- 16636082
TI  - Comparative in vitro activity of PGE 9262932 and fluoroquinolones against
      Canadian clinical Streptococcus pneumoniae isolates, including molecularly
      characterized ciprofloxacin-resistant isolates.
AB  - OBJECTIVES: The aim of this study was to assess the in vitro activity of the non
      fluorinated quinolone PGE 9262932 against Streptococcus pneumoniae isolates with
      various resistance phenotypes: ciprofloxacin-resistant, macrolide-resistant,
      penicillin-resistant and trimethoprim/sulfamethoxazole-resistant. METHODS: The in
      vitro activity of PGE 9262932 against 2585 recent Canadian S. pneumoniae isolates
      with various resistance phenotypes was determined and compared with that of
      gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. In particular, the
      activity of PGE 9262932 against ciprofloxacin-resistant isolates with defined
      parC and gyrA mutations was assessed. RESULTS: PGE 9262932 MIC90s were < or =
      0.015 mg/L for all S. pneumoniae and 0.12 mg/L for the ciprofloxacin-resistant
      isolates. Resistance to penicillin, macrolides or trimethoprim/sulfamethoxazole
      had little effect on the PGE 9262932 MICs. The quinolone MIC50/90s were only
      slightly affected by the presence of one parC or gyrA mutation, but increased 2-
      to 16-fold in the presence of mutations in both parC and gyrA, depending on the
      specific quinolone. With each quinolone resistance genotype, the order of
      activity, based on MIC90, against the ciprofloxacin-resistant isolates was PGE
      9262932, gemifloxacin, moxifloxacin, gatifloxacin and levofloxacin. CONCLUSIONS:
      PGE 9262932 was the most active quinolone against all S. pneumoniae isolates,
      regardless of resistance phenotype.

PMID- 16636083
TI  - tet(A)-mediated tetracycline resistance in porcine Bordetella bronchiseptica
      isolates is based on plasmid-borne Tn1721 relics.

PMID- 16636084
TI  - Impact of rapid in situ hybridization testing on coagulase-negative staphylococci
      positive blood cultures.
AB  - OBJECTIVES: To evaluate the impact of the rapid differentiation of Staphylococcus
      aureus from coagulase-negative staphylococci (CoNS) in blood cultures using
      peptide nucleic acid fluorescence in situ hybridization (PNA FISH) on vancomycin
      usage, length of patient hospital stay and hospital costs. DESIGN: This was a
      retrospective, cost-effective analysis of PNA FISH in its initial 3 month
      implementation period in 2004 in a 650 bed academic medical centre. Blood
      cultures with Gram-positive cocci in clusters (GPCC) that were negative for S.
      aureus using the PNA FISH assay were compared with an untested control group in
      the same period that had similar illness severity and location. We evaluated the
      effectiveness of the early identification of CoNS by ruling out S. aureus in
      conjunction with an antimicrobial team (AMT) on antimicrobial therapy, patient
      length of stay and hospital costs. RESULTS: A total of 139 blood cultures
      positive with GPCC had PNA FISH results while 84 in the control group did not.
      Evaluable criteria were met in 53 patients in the PNA FISH group and 34 in the
      control group. When comparing the results obtained from using the PNA FISH assay
      with those for the control group, there was a significant reduction in median
      length of hospital stay from 6 to 4 days (P < 0.05, CI 0.95-1.87) and a trend
      towards less vancomycin usage with a decrease in associated hospital costs of
      approximately Dollars 4000 per patient. CONCLUSIONS: The PNA FISH assay is rapid,
      accurate and reliable and in association with an AMT could decrease hospital
      length of stay in patients with CoNS bacteraemia in non-intensive care unit
      settings and prevent excessive vancomycin usage.

PMID- 16636085
TI  - Studies on the antimicrobial activity of cecropin A-melittin hybrid peptides in
      colistin-resistant clinical isolates of Acinetobacter baumannii.
AB  - OBJECTIVES: Acinetobacter baumannii has successfully developed resistance against
      all common antibiotics, including colistin, one of the last active drugs against
      this pathogen. We have tested whether the differences in lethal mechanism between
      polymyxin B and the cecropin A-melittin hybrid peptide CA(1-8)M(1-18), shown
      previously with a colistin-susceptible strain, can be exploited as a new
      chemotherapeutic alternative against colistin-resistant clinical isolates.
      Furthermore, the effect of capsule on the bactericidal activity of cecropin A
      melittin analogues (CAMs) was tested. METHODS: MICs and MBCs of the four CAMs
      were determined for 13 clinical isolates. The bactericidal activity of the
      antimicrobial peptides was measured using time-kill curves. The presence or
      absence of capsule was determined using Indian ink stain. RESULTS: The MIC ranges
      of CA(1-8)M(1-18) and three of its shortened analogues, namely CA(1-7)M(2-9), its
      Nalpha-terminal octanoylated analogue and CA(1-7)M(5-9), for A. baumannii strains
      were 2-8, 2-4, 2-8 and 4-4 mg/L, respectively. MBCs differed by a factor of two
      at the most. All of the cecropin A-melittin peptides showed bactericidal activity
      in time-kill curves against four A. baumannii strains. The bactericidal activity
      of CAMs was not affected by the presence of capsule. CONCLUSIONS: These results
      indicate that this class of peptides has a fast microbicidal effect on the
      colistin-resistant A. baumannii isolates, regardless of considerable structural
      variation among the four peptides and varying colistin MIC for the strains
      included in the study. Overall, the cecropin A-melittin peptides appear to be a
      promising alternative to overcome polymyxin resistance in A. baumannii.

PMID- 16636086
TI  - Adult stem cells, lung biology, and lung disease. NHLBI/Cystic Fibrosis
      Foundation Workshop.

PMID- 16636087
TI  - Evolving concepts in the measurement of treatment effects.
AB  - This is an interesting time in the evolution of clinical research, as the
      convergence of scientific, social, and technological advances influences the
      development of new measurement strategies and creates new challenges and
      opportunities in the evaluation of treatment outcomes. The purpose of this paper
      is to provide a brief overview of the forces of change influencing clinical
      research in general and measurement, specifically, discuss current challenges in
      the evaluation of treatment outcomes in chronic obstructive pulmonary disease and
      propose several areas for further research. Five key challenges are discussed:
      accuracy in the selection and measurement of endpoints; appropriate timing and
      recall; measurement efficiencies using aggregation techniques or item response
      theory; interpretation, including the debate concerning the minimal important
      difference; and the need for "real world" studies with real-world measures to
      understand treatment effectiveness. Each of these areas offers interesting
      challenges and opportunities for further development and research.

PMID- 16636088
TI  - Impact of chronic obstructive pulmonary disease exacerbations on patients and
      payers.
AB  - Chronic obstructive pulmonary disease (COPD) is not only an established major
      cause of mortality and morbidity but is increasing in worldwide prevalence
      despite current medical interventions. The natural history of COPD is punctuated
      by periods of acute symptomatic, physiologic, and functional deterioration or
      exacerbations. These events are responsible for considerable additional morbidity
      and mortality and impact on patients' long-term health status. Despite advances
      in understanding disease mechanisms and in treatment, exacerbations continue to
      be the major cause of COPD-associated hospitalization, and provision for their
      management incurs considerable health care costs. Although pharmacologic
      therapies may improve clinical outcomes, these benefits must be optimized by
      prompt diagnosis and delivery. This will require improved understanding of this
      complex disease by physicians and patients alike.

PMID- 16636089
TI  - Health status: what does it mean for payers and patients?
AB  - Disturbances to health can be divided broadly into limitations of basic
      activities of daily living (washing, dressing, etc.) that are common to all
      patients and other limitations that depend on individual circumstances. A
      distinction should be drawn between health status and health-related quality of
      life. Health status questionnaires are standardized for "typical patients," and
      this should be borne in mind when interpreting such scores from studies that give
      an average result using population-based measurements. Such studies give a good
      indication to payers of the average effects of a treatment, but provide no
      indication other than probability of benefit to individuals. This applies even
      more with health improvements that manifest uniquely in each patient. Two widely
      used disease-specific questionnaires in chronic obstructive pulmonary disease-the
      Chronic Respiratory Questionnaire and the St. George's Respiratory Questionnaire
      are health status, rather than quality of life, instruments. Health status scores
      from questionnaires provide measures of the effects of disease, not measures of
      the disease itself. The relationship between high health status score and
      increased risk of dying is due to the fact that both reflect underlying disease
      activity. In therapeutic studies, health status improves because the underlying
      disease activity has been moderated by therapy. Improved health does not improve
      mortality or morbidity per se. It is also important to appreciate that the impact
      of any measured change in health may also be determined by the patient's baseline
      state.

PMID- 16636090
TI  - Health economics of chronic obstructive pulmonary disease.
AB  - Studies describing the economic impact of chronic obstructive pulmonary disease
      (COPD) are used for several purposes. There can, however, be limitations as costs
      based on results of a clinical trial are likely to be significantly different
      from real world practice. Sometimes, it may be more useful to capture the costs
      of the important components accurately rather than the often unachievable aim of
      capturing every cost however small. Burden of illness studies can help identify
      clinical targets or patterns of care-for example, hospitalization-that are major
      health care cost drivers. In the United Kingdom, burden of COPD studies suggest
      an annual cost of 781 pounds sterlings- 1,154 pounds sterlings per patient. Cost
      analyses can be divided into four types: cost minimization, cost-effectiveness,
      cost benefit, and cost utility. Utilities such as quality-adjusted life year
      (QALY) measure the effectiveness of different therapies, and can be obtained in
      various ways and in different populations, potentially leading to significant
      differences in the results. Payers often apply cost per QALY thresholds when
      assessing whether a new therapy should be used or not. In the United Kingdom, it
      is accepted that there is a sigmoid relationship between the cost per QALY and
      the likelihood of a therapy being recommended, with a lower inflection between
      5,000 pounds sterlings and 15,000 sterlings, below which rejection is unlikely
      and an upper inflection between 25,000 pounds sterlings and 35,000, above which
      acceptance is unlikely, but not impossible. On this basis, pulmonary
      rehabilitation and inhaled steroids are unlikely to be rejected but lung volume
      reduction surgery may be.

PMID- 16636091
TI  - Mechanisms and measurement of dyspnea in chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) describe their
      breathlessness as related to the work and effort associated with breathing.
      Current evidence suggests that the perception of dyspnea is due to a "mismatch"
      between the outgoing motor command from the central nervous system and the
      corresponding afferent information from chemoreceptors and/or mechanoreceptors.
      To measure the severity of dyspnea the principles of psychophysics (stimulus -->
      response relationship) can be applied. One approach is to consider activities of
      daily living as a putative stimulus. Although this method relies on patient
      recall and description of daily tasks, ability to function, as well as time and
      effort to complete an activity, select clinical instruments have demonstrated
      appropriate measurement criteria in randomized clinical trials involving patients
      with COPD. Another approach is for a patient to report the intensity of dyspnea
      during exercise, and current practice is to provide ratings each minute "on cue"
      during the exercise test. A computerized system has been developed whereby the
      person can report ratings spontaneously and continuously by moving a computer
      mouse that adjusts a vertical bar adjacent to 0-10 category-ratio scale
      positioned on a monitor. With this continuous method the patient reports twice
      the number of dyspnea ratings during exercise compared with discrete ratings each
      minute. Patient-reported dyspnea based on activities of daily living and exercise
      testing provides distinct but complimentary information.

PMID- 16636092
TI  - Dynamic hyperinflation: is it worth measuring?
AB  - A reduced exercise capacity is an important determinant of health status and an
      independent prognostic marker in patients with chronic obstructive pulmonary
      disease. The inability to increase expiratory flow at the resting end-expiratory
      lung volume in the face of expiratory-flow limitation means that end-expiratory
      lung volume must increase if gas exchange is to be maintained near normal values.
      This phenomenon is usually referred to as dynamic hyperinflation. The change in
      operating lung volumes during exercise is related to the intensity of
      breathlessness. Treatments such as bronchodilators that increase inspiratory
      capacity or supplemental oxygen, which reduces ventilatory demand, decrease the
      degree of dynamic hyperinflation at any external workload. However, dynamic
      hyperinflation is not seen universally in patients with chronic obstructive
      pulmonary disease as some adopt different breathing patterns when they exercise,
      or respond to inhaled bronchodilators by changing their pattern of abdominal
      muscle activation, a behavior that can be counterproductive. Finally, dynamic
      hyperinflation can be reduced when, for example, breathing oxygen after exercise
      without changes in dyspnea, as other factors are more important determinants of
      this symptom in these circumstances. Dynamic hyperinflation can be reliably
      measured from the inspiratory capacity maneuver in many laboratories. Although
      knowledge about this variable gives great insight into the mechanisms of therapy,
      its routine measurement cannot currently be recommended as it does not appear to
      add additional clinical data beyond those available in present laboratory
      exercise testing protocols.

PMID- 16636093
TI  - Pathophysiology of exacerbations of chronic obstructive pulmonary disease.
AB  - Smokers with stable chronic obstructive pulmonary disease have a chronic
      inflammation of the entire tracheobronchial tree characterized by an increased
      number of macrophages and CD8 T lymphocytes in the airway wall and of neutrophils
      in the airway lumen. Exacerbations of chronic obstructive pulmonary disease are
      considered to reflect worsening of the underlying chronic inflammation of the
      airways, caused mainly by viral and bacterial infections and air pollution.
      During exacerbations, the inflammatory cellular pattern changes, with a further
      increase of eosinophils and/or neutrophils and various inflammatory mediators-
      for example, cytokines (tumor necrosis factor-alpha, RANTES [regulated upon
      activation normal T cell-expressed and secreted], and eotaxin-1), chemokines
      (CXCL5 [ENA-78], CXCL8), chemokine receptors (CCR3, CXCR1, and CXCR2), adhesion
      molecules (E-selectin and ICAM-1), and markers of oxidative stress (H(2)O(2) and
      8-isoprostane, glutathione depletion). Worsening of inflammation is considered
      responsible for the deterioration of lung function and clinical status during
      exacerbations.

PMID- 16636094
TI  - Clinical assessment, staging, and epidemiology of chronic obstructive pulmonary
      disease exacerbations.
AB  - Patients presenting with an exacerbation of chronic obstructive pulmonary disease
      (COPD) are initially assessed to ensure that a proper diagnosis has been made and
      that relevant differential diagnoses are excluded. Although guidelines provide
      indicators for use, very little systematic research has been done in initial
      assessment of COPD exacerbations. Next, the assessment should aim at stratifying
      patients for risk of poor outcome. For this, predictors of poor prognosis as well
      as knowledge of favorable treatments can be used. However, no formal and
      validated staging system exists today. Given the frequency and impact of COPD
      exacerbations, there seems to be a need for systematic research in this area.

PMID- 16636095
TI  - Prevention of exacerbations: how are we doing and can we do better?
AB  - Prevention of exacerbations of chronic obstructive pulmonary disease (COPD) can
      involve removing the cause or reducing the patient's vulnerability to the cause.
      This article addresses the following issues: What is the problem during an
      exacerbation, what are the causes of an exacerbation, what can prevent
      exacerbations, and who are we? The difference between a patient with COPD during
      an exacerbation and after recovery is small. It is unlikely that patients with
      early COPD experience less exposure to exacerbation causes than those with severe
      disease; it is just that the consequences are more severe for those with severe
      disease. Interventions that produce small absolute benefits can therefore have a
      disproportionately large effect on exacerbation reduction. Recognized causes
      include season, cold weather, pollution events, bacterial infection, viral
      infection, and treatment withdrawal. Countries with warmer climates have much
      larger mortality in cold weather than those with colder climates. Reducing
      exacerbations in more temperate climates may be altered as much by changes in
      clothing and bedroom heating as by changes in treatment. Taking more exercise in
      cold weather may be the underlying reason for the reduction of exacerbations
      after pulmonary rehabilitation. Influenza vaccination reduces influenza severity
      and reduces transmission from health care workers to patients. There are a number
      of pharmacologic interventions shown to reduce (the effect of) exacerbations,
      including inhaled corticosteroids, long-acting beta-agonists, long-acting
      anticholinergics, mucolytics, and perhaps antibiotics that reduce Haemophilus
      carriage. The effect of the bronchodilators is additive to inhaled
      corticosteroids; how far the other interventions are complementary is unclear. So
      far, we have had a very medical response to COPD exacerbations. Altering social
      and behavioral aspects is likely to be complementary.

PMID- 16636096
TI  - Approaches to improving health status in chronic obstructive pulmonary disease:
      one or several?
AB  - Health outcomes represent a broad group of endpoints used in clinical practice to
      assess the efficacy and effectiveness of interventions and to assess disease
      outcomes. Health status is one of the widely applied patient-reported health
      outcomes. The outcome of a variety of interventions, targeting local impairment
      or local airway inflammation, is evaluated by health status measurements; these
      global or summative outcomes indeed quantify the overall effect of a number of
      biological processes. Targeting the systemic compartment to improve health status
      is already widely applied in the domain of pulmonary rehabilitation. Challenging
      developments targeting systemic inflammation and biological processes related to
      systemic inflammation are particularly addressed in this review.

PMID- 16636097
TI  - Improving dyspnea in chronic obstructive pulmonary disease: optimal treatment
      strategies.
AB  - Chronic obstructive pulmonary disease (COPD) is a common disease with a global
      impact in terms of morbidity and mortality. Patients usually consult their doctor
      because of symptoms, and among those, dyspnea at rest or under exercise is one of
      the most common. The sensation of dyspnea is experienced differently among
      individuals with COPD and may be based on diverse factors, such as muscle
      fatigue, patient perception, or trapped volumes. Treatment algorithms for COPD
      emphasize a stepwise approach to therapy depending on the severity of the
      disease, which, for reasons of convenience, is primarily based on spirometric
      impairment. Drugs that alter bronchial smooth muscle tone and increase
      inspiratory capacity have clinical efficacy for the dyspneic patient, most likely
      based on their effect on lung function, whereas the effects of antiinflammatory
      therapy with inhaled corticosteroids is more difficult to explain. The following
      short review aims to give an overview of the available clinical information of
      clinical trials performed over the last couple of years.

PMID- 16636098
TI  - Chronic obstructive pulmonary disease: linking outcomes and pathobiology of
      disease modification.
AB  - Recent guidelines define chronic obstructive pulmonary disease (COPD) as a
      preventable and treatable disease characterized by airflow limitation and
      systemic consequences. Airflow limitation in COPD worsens over years as assessed
      by the forced expiratory volume in one second (FEV(1)). Regardless, while it is
      likely that cardiovascular and other systemic components also worsen as COPD
      progresses, there are no accepted or validated outcomes to measure such
      pathophysiologic changes as they relate to COPD disease progression. It is clear
      that health status in COPD is more closely related to levels of patients'
      physical functional capacity than it is to changes in FEV(1). Furthermore, the
      relative contributions of pathoanatomic changes such as small airways fibrosis
      and pulmonary emphysema to declining airflow remain unknown. These features may
      even progress at different rates in the same individuals. Although stopping
      smoking is the only intervention shown to alter the relentless progression of
      COPD, the resultant slowing of FEV(1) decline takes several years to evince and
      requires at least 1,000 subjects to demonstrate annual therapeutic benefits of as
      little as 20 ml. The FEV(1) cannot distinguish between peribronchiolar fibrosis
      and emphysema and it is feasible that, as techniques are developed and validated,
      lung imaging methodologies may become important and sensitive outcomes measures
      of time- and age-dependent lung structural changes in COPD. The development of
      biomarkers of lung damage, pulmonary inflammation, and systemic disease will be
      essential to our further understanding of the natural history of COPD and the
      discovery of new, effective treatments for its progression.

PMID- 16636099
TI  - Reductions in levels of the Alzheimer's amyloid beta peptide after oral
      administration of ginsenosides.
AB  - For millennia, ginseng and some of its components have been used to treat a wide
      variety of medical conditions, including age-related memory impairment. Because
      of its purported effects and apparently low rate of side effects, ginseng remains
      one of the top selling natural product remedies in the United States. Given its
      potential role for improving age-related memory impairments and its common use in
      China for the treatment of Alzheimer's disease-like symptoms, we analyzed the
      effects of commercially available preparations of ginseng on the accumulation of
      the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In
      this model system, ginseng treatment resulted in a significant reduction in the
      levels of Abeta in the conditioned medium. We next examined the effects of
      several compounds isolated from ginseng and found that certain ginsenosides
      lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3
      having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we
      found that three of these isolated components, ginsenoside Rg1, Rg3, and RE,
      resulted in significant reductions in the amount of Abeta detected in the brains
      of animals after single oral doses of these agents. The results indicate that
      ginseng itself, or purified ginsenosides, may have similarly useful effects in
      human disease.

PMID- 16636100
TI  - Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin
      L knockout mice.
AB  - Although lysosomal proteases are expressed in the heart at considerable levels,
      their specific functions in this organ remain elusive. Mice deficient for the
      lysosomal cysteine protease cathepsin L (CTSL) develop a late onset dilated
      cardiomyopathy (DCM) that is characterized by cardiac chamber dilation, fibrosis,
      and impaired cardiac contraction at 12 month of age. Investigation of the
      pathogenic sequence of DCM in ctsl-/- mice revealed numerous dysmorphic lysosome
      like structures in heart muscle as early as 3 days after birth, whereas skeletal
      muscle was not affected. Labeling of the acidic cell compartment of neonatal
      cardiomyocytes and detection of lysosomal markers after subcellular fractionation
      confirmed increased lysosome content in CTSL deficient myocardium; however,
      specific storage materials were not detected. The myocardium of ctsl+/+ and ctsl
      /- mice revealed no differences in incidence of cell death, proliferation, and
      capillary density during DCM progression. However, an observed increase in mRNA
      expression of natriuretic peptides in young adult mice indicates the activation
      of the adaptive "fetal" gene program, while proteome analysis revealed decreased
      levels of the sarcomere-associated proteins alpha-tropomyosin, desmin, and
      calsarcin 1, as well as considerable changes of metabolic enzymes. Bioinformatic
      pathway analysis suggested a switch to anaerobic catabolism and impairment of
      mitochondrial respiration. This interpretation was supported by a 50% reduction
      in resting state oxygen consumption and impaired respiration capacity in ctsl-/-
      myocardial homogenates. In summary, the data indicate an essential role of CTSL
      in maintaining the structure of the endosomal/lysosomal compartment in
      cardiomyocytes. Lysosomal impairment in ctsl-/- hearts results in metabolic and
      sarcomeric alterations that promote DCM development.

PMID- 16636101
TI  - Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression
      in astrocytic cultures and promotes survival of dopaminergic neurons.
AB  - Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is currently used as
      an antiparkinsonian drug. We have shown previously that APO stimulates synthesis
      and release of multiple trophic factors, such as brain-derived neurotrophic
      factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), in both
      mesencephalic and striatal neurons, thereby effectively preventing dopaminergic
      neuron loss in vitro. The present study was designed to investigate the effects
      of APO on fibroblast growth factor-2 (FGF-2) expression and regulation in
      astrocytes, and furthermore, to identify signaling mechanisms underlying these
      effects. Here, we show that FGF-2 expression is robustly induced in cultured
      astrocytes in response to APO. FGF-2 expression was proportional to APO
      concentration and time-dependent. Conversely, treatment with S-APO, a derivative
      of R-APO lacking DA receptor agonist activity, did not alter FGF-2 levels. APO
      treatment resulted in enhanced cytosol FGF-2 immunoreactivity, export of high MW
      forms of FGF-2 to the cytoplasm from the nucleus and increased extracellular
      release of FGF-2. Interestingly, both high and low MW forms of FGF-2 were
      detectable in conditioned medium of APO-treated cultures. This APO-induced effect
      was correlated with activation of D1 and D2 receptors, as it could be either
      mimicked by dopamine receptor agonists (SKF38393, quinpirole) or partially
      blocked by antagonists (SCH23390, SKF83566, haloperidol). Activation of the D1
      receptor preferentially increased PKA activity, whereas activation of the D2
      receptor only promoted phosphorylation of MAPK. Importantly, APO-modulated FGF-2
      expression was independent of Akt/phosphoinositide 3-kinase signaling. These data
      suggest that APO can enhance biosynthesis and release of FGF-2 through activation
      of dopamine receptors in striatal astrocytes. Both cAMP/PKA and MEK/MAPK
      signaling cascades are major steps mediating this process.

PMID- 16636102
TI  - Control of intestinal motility by the Ca(v)1.2 L-type calcium channel in mice.
AB  - The Ca(v)1.2 L-type Ca2+ channel is the dominant voltage-activated Ca2+ channel
      in heart and smooth muscle. The functional significance of this channel was
      studied in intestinal smooth muscle from mice carrying a smooth muscle-specific,
      conditional inactivation of the Ca(v)1.2 gene (Ca(v)1.2SMACKO mice). Inactivation
      was complete within 4 wk after tamoxifen treatment and confirmed by RT-PCR,
      Western blot and functional analysis. Ca(v)1.2SMACKO mice show reduced feces
      excretion, absence of rhythmic contractions in small and large intestinal muscle
      and signs of paralytic ileus. Extracellular field stimulation evoked smaller
      contractions in jejunum muscles from Ca(v)1.2SMACKO than from CTR mice, whereas
      carbachol-induced contractions of similar magnitude in both muscles. The Ca2+
      needed for contraction in jejunum was provided mainly by Ca(v)1.2 channels and by
      store-operated channels in muscles from CTR and Ca(v)1.2SMACKO mice,
      respectively. In conclusion, the Ca(v)1.2 channel is essential for
      electromechanical coupling and important for pharmaco-mechanical coupling in
      intestinal smooth muscle and cannot be substituted functionally by other Ca2+
      entry pathways.

PMID- 16636103
TI  - Abeta induces cell death by direct interaction with its cognate extracellular
      domain on APP (APP 597-624).
AB  - Amyloid beta-peptide (Abeta) is postulated to play a central role in the
      pathogenesis of Alzheimer's disease. We recently proposed a pathway of Abeta
      induced toxicity that is APP dependent and involves the facilitation of APP
      complex formation by Abeta. The APP-dependent component requires cleavage of APP
      at position 664 in the cytoplasmic domain, presumably by caspases or caspase-like
      proteases, with release of a potentially cytotoxic C31 peptide. In this study we
      show that Abeta interacted directly and specifically with membrane-bound APP to
      facilitate APP homo-oligomerization. Using chimeric APP molecules, this
      interaction was shown to take place between Abeta and its homologous sequence on
      APP. Consistent with this finding, we demonstrated that Abeta also facilitated
      the oligomerization of beta-secretase cleaved APP C-terminal fragment (C99). We
      found that the YENPTY domain in the APP cytoplasmic tail and contained within C31
      is critical for this cell death pathway. Deletion or alanine- scanning
      mutagenesis through this domain significantly attenuated cell death apparently
      without affecting either APP dimerization or cleavage at position 664. This
      indicated that sequences within C31 are required after its release from APP. As
      the YENPTY domain has been shown to interact with a number of cytosolic adaptor
      molecules, it is possible that the interaction of APP, especially dimeric forms
      of APP, with these molecules contribute to cell death.

PMID- 16636104
TI  - Granzyme B mediates neurotoxicity through a G-protein-coupled receptor.
AB  - Neuroinflammatory diseases such as multiple sclerosis (MS) are characterized by
      focal regions of demyelination and axonal loss associated with infiltrating T
      cells. However, the role of activated T cells in causing neuronal injury remains
      unclear. CD4 and CD8 T cells were isolated from normal donors and polyclonally
      activated using plate-bound anti-CD3 and soluble anti-CD28. The conditioned T
      cell supernatants caused toxicity to cultured human fetal neurons, which could be
      blocked by immunodepleting the supernatants of granzyme B (GrB). Recombinant GrB
      also caused toxicity in neurons by caspase-dependent pathways but no toxicity was
      seen in astrocytes. The neurotoxicity was independent of perforin and could not
      be blocked by mannose-6-phosphate. However, GrB-induced neurotoxicity was
      sensitive to pertussis toxin, implicating the stimulation of Gialpha protein
      coupled receptors. GrB caused a decrease in cAMP levels but only modest increases
      in intracellular calcium. The effect on intracellular calcium could be markedly
      potentiated by stromal-derived factor 1alpha. GrB-induced neurotoxicity could
      also be blocked by vitamin E and a neuroimmunophilin ligand. In conclusion, GrB
      may be an important mediator of neuronal injury in T cell-mediated
      neuroinflammatory disorders.

PMID- 16636105
TI  - Ganglioside GM3 is involved in neuronal cell death.
AB  - Gangliosides abundant in the nervous system have been implicated in a broad range
      of biological functions, including the regulation of cell proliferation and
      death. Glutamate-induced cell death, which is accompanied by an accumulation of
      reactive oxygen species (ROS), is a major contributor to pathological cell death
      within the nervous system. However, the mechanism underlying this neuronal cell
      death has not been fully elucidated. In this study, we report that ganglioside
      GM3 is involved in neuronal cell death. GM3 was up-regulated in the mouse
      hippocampal cell line HT22 death caused by glutamate. Increment in GM3 levels by
      both the exogenous addition of GM3 and the overexpression of the GM3 synthase
      gene induced neuronal cell death. Overexpression of GM3 synthase by
      microinjecting mRNA into zebrafish embryos resulted in neuronal cell death in the
      central nervous system (CNS). Conversely, RNA interference-mediated silencing of
      GM3 synthase rescued glutamate-induced neuronal death, as evidenced by the
      inhibition of massive ROS production and intracellular calcium ion influx. 12
      lipoxygenase (12-lipoxygenase) (12-LOX) was recruited to glycosphingolipid
      enriched microdomains (GEM) in a GM3-dependent manner during oxidative glutamate
      toxicity. Our findings suggest that GM3 acts as not only a mediator of oxidative
      HT22 death by glutamate but also a modulator of in vivo neuronal cell death.

PMID- 16636106
TI  - Endomorphin-2, an endogenous tetrapeptide, protects against Abeta1-42 in vitro
      and in vivo.
AB  - The underlying cause of Alzheimer's disease (AD) is thought to be the beta
      amyloid aggregates formed mainly by Abeta1-42 peptide. Protective pentapeptides
      [e.g., Leu-Pro-Phe-Phe-Asp (LPFFD)] have been shown to prevent neuronal toxicity
      of Abeta1-42 by arresting and reversing fibril formation. Here we report that an
      endogenous tetrapeptide, endomorphin-2 (End-2, amino acid sequence: YPFF),
      defends against Abeta1-42 induced neuromodulatory effects at the cellular level.
      Although End-2 does not interfere with the kinetics of Abeta fibrillogenesis
      according to transmission electron microscopic studies and quasielastic light
      scattering measurements, it binds to Abeta1-42 during aggregation, as revealed by
      tritium-labeled End-2 binding assay and circular dichroism measurements. The
      tetrapeptide attenuates the inhibitory effect on cellular redox activity of
      Abeta1-42 in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazolyl-2)
      2,-5-diphenyltetrazolium bromide (MTT) assay. In vitro and in vivo
      electrophysiological experiments show that End-2 also protects against the field
      excitatory postsynaptic potential attenuating and the NMDA-evoked response
      enhancing effect of Abeta1-42. Studies using [D-Ala (2), N-Me-Phe (4), Gly (5)
      ol]-enkephalin (DAMGO), a mu-opioid receptor agonist, show that the protective
      effects of the tetrapeptide are not mu-receptor modulated. The endogenous
      tetrapeptide End-2 may serve as a lead compound for the drug development in the
      treatment of AD.

PMID- 16636107
TI  - Antagonizing inactivated tumor suppressor genes and activated oncogenes by a
      versatile transgenesis system: application in mantle cell lymphoma.
AB  - A broad range of malignant diseases, such as mantle cell lymphoma (MCL), is
      associated with complex genomic alterations, demanding multimodal functional
      testing of candidate genes. To assess such candidate disease genes, we have
      developed a bidirectional targeted transgenesis tool, which allows well
      controlled modulation of individual gene activities within a cellular MCL system.
      The engineered versatile transgenesis system permits functional analysis of
      virtually any candidate gene: for tumor suppressor genes by complementation via
      integration of respective genomic DNA or for oncogenes by inactivation via
      integrated shRNA coding plasmids. Complementation by genomic DNA ensures wild
      type (WT) regulated gene expression, whereas genomic integration of shRNA coding
      inserts by an advanced RNAi-strategy mediates specific knock-down of gene
      expression. Site-specific genomic integration of an unmodified BAC, which
      contains the CDKN2A/B genes absent in the MCL model system, restored CDKN2A/B
      expression resulting in the inhibition of cell proliferation. CCND1, strongly
      overexpressed in the model system, was down-regulated via shRNA expression, again
      inhibiting proliferation. Notably, the presented site-specific shRNA-strategy
      circumvents interference by IFN-response induced when using other RNAi gene knock
      down methods. In conclusion, we here demonstrate that adequate restoration of a
      range of different gene activities yields in a desired antiproliferative effect
      in MCL-derived cells. By antagonizing inactivated tumor suppressor genes or
      activated oncogenes, the presented approach can be readily used for the
      functional analysis of a broad range of disease-related genetic defects.

PMID- 16636108
TI  - Embryonic stem cells utilize reactive oxygen species as transducers of mechanical
      strain-induced cardiovascular differentiation.
AB  - Growing stem cells are subjected to mechanical forces, which may initiate
      differentiation programs. Mechanical strain stimulated cardiovascular
      differentiation of mouse embryonic stem (ES) cells as evaluated by quantification
      of contracting cardiac foci and capillary areas, respectively. Mechanical strain
      rapidly elevated intracellular reactive oxygen species (ROS). After 24 h up
      regulation of NADPH oxidase subunits p22-phox, p47-phox, p67-phox, and Nox-4 as
      well as Nox-1 and Nox-4 mRNA was observed. In parallel, mechanical strain
      increased hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial
      growth factor (VEGF) mRNA and protein as well as MEF2C and GATA-4 mRNA, which are
      involved in cardiovascular development. Furthermore, phosphorylation of
      extracellular-regulated kinase 1,2 (ERK1,2), p38, and c-jun N-terminal kinase (c
      Jun NH2-terminal kinase (JNK)) was observed. Stimulation of cardiovascular
      commitment, HIF-1alpha, VEGF, and MEF2C expression as well as MAPK activation
      were abolished by free radical scavengers, whereas GATA-4 expression was
      increased. Cardiomyogenesis was inhibited by the p38 inhibitor SB203580, the
      ERK1,2 inhibitor UO126, and the JNK inhibitor SP600125.
      Vasculogenesis/angiogenesis was blunted following inhibition of ERK1,2 and JNK,
      whereas p38 inhibition was ineffective. Our data outline a role of ROS as
      mechanotransducing molecules in mechanical strain-stimulated cardiovascular
      differentiation of ES cells, and point toward a microenvironment of elevated ROS
      required for signaling cascades initiating cardiovascular differentiation
      programs.

PMID- 16636109
TI  - Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery
      in paraplegic rats via an increased BDNF expression by endogenous macrophages.
AB  - Macrophages (monocytes/microglia) could play a critical role in central nervous
      system repair. We have previously found a synchronism between the regression of
      spontaneous axonal regeneration and the deactivation of macrophages 3-4 wk after
      a compression-injury of rat spinal cord. To explore whether reactivation of
      endogenous macrophages might be beneficial for spinal cord repair, we have
      studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF)
      in the same paraplegia model and in cell cultures. There was a significant,
      though transient, improvement of locomotor recovery after a single delayed
      intraperitoneal injection of 2 microg GM-CSF, which also increased significantly
      the expression of Cr3 and brain-derived neurotrophic factor (BDNF) by macrophages
      at the lesion site. At longer survival delays, axonal regeneration was
      significantly enhanced in GM-CSF-treated rats. In vitro, BV2 microglial cells
      expressed higher levels of BDNF in the presence of GM-CSF and neurons cocultured
      with microglial cells activated by GM-CSF generated more neurites, an effect
      blocked by a BDNF antibody. These experiments suggest that GM-CSF could be an
      interesting treatment option for spinal cord injury and that its beneficial
      effects might be mediated by BDNF.

PMID- 16636110
TI  - Phenylthiocarbamide: a 75-year adventure in genetics and natural selection.

PMID- 16636111
TI  - New roles for model genetic organisms in understanding and treating human
      disease: report from the 2006 Genetics Society of America meeting.
AB  - Fundamental biological knowledge and the technology to acquire it have been
      immeasurably advanced by past efforts to understand and manipulate the genomes of
      model organisms. Has the utility of bacteria, yeast, worms, flies, mice, plants,
      and other models now peaked and are humans poised to become the model organism of
      the future? The Genetics Society of America recently convened its 2006 meeting
      entitled "Genetic Analysis: Model Organisms to Human Biology" to examine the
      future role of genetic research. (Because of time limitations, the meeting was
      unable to cover the substantial contributions and future potential of research on
      model prokaryotic organisms.) In fact, the potential of model-organism-based
      studies has grown substantially in recent years. The genomics revolution has
      revealed an underlying unity between the cells and tissues of eukaryotic
      organisms from yeast to humans. No uniquely human biological mechanisms have yet
      come to light. This common evolutionary heritage makes it possible to use
      genetically tractable organisms to model important aspects of human medical
      disorders such as cancer, birth defects, neurological dysfunction, reproductive
      failure, malnutrition, and aging in systems amenable to rapid and powerful
      experimentation. Applying model systems in this way will allow us to identify
      common genes, proteins, and processes that underlie human medical conditions. It
      will allow us to systematically decipher the gene-gene and gene-environment
      interactions that influence complex multigenic disorders. Above all, disease
      models have the potential to address a growing gap between our ability to collect
      human genetic data and to productively interpret and apply it. If model organism
      research is supported with these goals in mind, we can look forward to diagnosing
      and treating human disease using information from multiple systems and to a
      medical science built on the unified history of life on earth.

PMID- 16636112
TI  - Assessing the effects of human mixing patterns on human immunodeficiency virus-1
      interhost phylogenetics through social network simulation.
AB  - Geneticists seeking to understand HIV-1 evolution among human hosts generally
      assume that hosts represent a panmictic population. Social science research
      demonstrates that the network patterns over which HIV-1 spreads are highly
      nonrandom, but the effect of these patterns on the genetic diversity of HIV-1 and
      other sexually transmitted pathogens has yet to be thoroughly examined. In
      addition, interhost phylogenetic models rarely account explicitly for genetic
      diversity arising from intrahost dynamics. This study outlines a graph-theoretic
      framework (exponential random graph modeling, ERGM) for the estimation,
      inference, and simulation of dynamic partnership networks. This approach is used
      to simulate HIV-1 transmission and evolution under eight mixing patterns
      resembling those observed in empirical human populations, while simultaneously
      incorporating intrahost viral diversity. Models of parametric growth fit
      panmictic populations well, yielding estimates of total viral effective
      population on the order of the product of infected host size and intrahost
      effective viral population size. Populations exhibiting patterns of nonrandom
      mixing differ more widely in estimates of effective population size they yield,
      however, and reconstructions of population dynamics can exhibit severe errors if
      panmixis is assumed. I discuss implications for HIV-1 phylogenetics and the
      potential for ERGM to provide a general framework for addressing these issues.

PMID- 16636113
TI  - Evolution of resistance during clonal expansion.
AB  - Acquired drug resistance is a major limitation for cancer therapy. Often, one
      genetic alteration suffices to confer resistance to an otherwise successful
      therapy. However, little is known about the dynamics of the emergence of
      resistant tumor cells. In this article, we consider an exponentially growing
      population starting from one cancer cell that is sensitive to therapy. Sensitive
      cancer cells can mutate into resistant ones, which have relative fitness alpha
      prior to therapy. In the special case of no cell death, our model converges to
      the one investigated by Luria and Delbruck. We calculate the probability of
      resistance and the mean number of resistant cells once the cancer has reached
      detection size M. The probability of resistance is an increasing function of the
      detection size M times the mutation rate u. If Mu << 1, then the expected number
      of resistant cells in cancers with resistance is independent of the mutation rate
      u and increases with M in proportion to M(1-1/alpha) for advantageous mutants
      with relative fitness alpha>1, to l nM for neutral mutants (alpha = 1), but
      converges to an upper limit for deleterious mutants (alpha<1). Further, the
      probability of resistance and the average number of resistant cells increase with
      the number of cell divisions in the history of the tumor. Hence a tumor subject
      to high rates of apoptosis will show a higher incidence of resistance than
      expected on its detection size only.

PMID- 16636114
TI  - United Kingdom collaborative randomized trial of neonatal extracorporeal membrane
      oxygenation: follow-up to age 7 years.
AB  - OBJECTIVE: The UK Collaborative ECMO trial provided an opportunity to describe
      mortality and morbidity associated with a neonatal ECMO policy compared with
      conventional management. The improved survival in the ECMO group was not offset
      by an increase in disability at 4 years, but the children were too young to
      assess educational and other longer-term impacts. The objective of this study was
      to assess the longer-term impact of these policies at age 7 years. METHODS: A
      psychologist assessed 90 of the 100 children available for follow-up without
      prior knowledge of treatment allocation. The assessments took place at the
      children's schools within 3 months of their 7th birthdays. RESULTS: Sixty-eight
      of 89 (76%) children recorded a cognitive level within the normal range. Learning
      problems were similar in the 2 groups, and there were notable difficulties with
      spatial and processing tasks. A higher respiratory morbidity and increased risk
      of behavioral problems among children treated conventionally persisted.
      Progressive sensorineural hearing loss was found in both groups. CONCLUSIONS: The
      underlying disease processes appear to be the major influence on morbidity at 7
      years. The beneficial influence of an ECMO policy is still present at 7 years.

PMID- 16636115
TI  - Pediatric cinnarizine overdose and toxicokinetics.
AB  - Cinnarizine, a piperazine derivative, is a widely prescribed medication for the
      treatment of vestibular disorders and motion sickness. Cinnarizine has
      antihistaminic, antiserotoninergic, antidopaminergic, and calcium channel
      blocking properties. We present the first report in the English literature of
      cinnarizine poisoning and toxicokinetics. A 30-month-old toddler ingested 225 mg
      of cinnarizine, 18 times the recommended dose for older children. Four hours
      later, she became jittery with a wide-based gait and vomited 3 times. She was
      examined by her family physician, who reported stupor and twitching in both
      hands. On admission to the hospital, 6 hours after the ingestion, she was
      stuporous and had 3 short, generalized tonic-clonic convulsions that were
      controlled with a single dose of midazolam. Full clinical recovery was seen 10
      hours after ingestion. Serum cinnarizine levels were 7407, 2629, and 711 ng/mL on
      admission and at 4 and 12 hours thereafter, respectively, 26.9 times higher than
      the therapeutic levels in adults. Elimination rate constant, calculated by linear
      regression of the ln concentrations of the 3 data points, was 0.19. Half-life,
      calculated from the equation t(1/2) = 0.693/kel, where kel is the elimination
      rate constant, was 3.65 hours. The manufacturing company revealed that their
      database contains 23 reports of cinnarizine overdose (adult and children),
      received between 1972 and 2004. Clinically, these cases reflect mainly symptoms
      of alterations in consciousness ranging from somnolence to stupor and coma,
      vomiting, extrapyramidal symptoms, and hypotonia. In a small number of young
      children, convulsions developed; recovery was uneventful in 4 cases and not
      reported in 1. The neurologic complication may be explained by the antihistaminic
      effect of cinnarizine because central nervous system depression and convulsions
      are known complications of antihistaminic overdose. It is hypothesized that
      cinnarizine-induced convulsions also are related to the antidopaminergic effect
      of the drug. Apart from the convulsions, no other adverse effects related to
      calcium channel-blocking properties, such as bradycardia or hemodynamic
      instability, were observed. Pediatric patients with cinnarizine overdose need to
      be observed in a health care facility for potential neurologic complications and
      be treated symptomatically. The delay to onset of clinical effect should be
      considered in the observation period.

PMID- 16636116
TI  - Transient hemophagocytosis with deficient cellular cytotoxicity, monoclonal
      immunoglobulin M gammopathy, increased T-cell numbers, and hypomorphic NEMO
      mutation.
AB  - X-linked osteopetrosis, anhydrotic ectodermal dysplasia, and immunodeficiency (XL
      O-EDA-ID) is a disorder that is caused by hypomorphic mutations in the nuclear
      factor kappaB essential modulator (NEMO). These mutations lead to an impaired NF
      kappaB activation. In vitro analyses and studies in animal models show that
      inhibition of NF-kappaB leads to a decrease of cytokine production and T-cell
      proliferation. Patients classically display poor or delayed inflammatory response
      to infections. We describe a boy with XL-O-EDA-ID, 1167-1168insC NEMO mutation,
      and recurrent infections. In early infancy, he experienced hemophagocytosis with
      transient deficiency of natural killer activity. Increased immunoglobulin M
      levels in blood resulted from a monoclonal immunoglobulin M gammopathy. Blood T
      cell numbers were constantly increased, most probably resulting from a peripheral
      T-cell expansion. Our observations suggest that patients with hypomorphic NEMO
      mutations and repeated infections may experience inflammatory dysregulation.

PMID- 16636117
TI  - Surgical remission of pituitary adenomas confined to the neurohypophysis in
      Cushing's disease.
AB  - CONTEXT: Partial or total removal of the pituitary cures 60-80% of patients with
      Cushing's disease (CD) in whom an adenoma cannot be identified at surgery. Many
      patients who fail complete or partial hypophysectomy are cured by sellar and
      parasellar irradiation. DESIGN/PATIENTS: As part of a series of prospective
      studies of CD, we identified 12 patients (34.5 +/- 19.9 yr; 11 females; four
      children) with tumors located completely within the neurohypophysis among 730
      patients undergoing surgery for CD. SETTING: The study was conducted at a
      tertiary referral center at a clinical research hospital. RESULTS: All 12
      patients had clinical and biochemically defined CD. Tumor was visible at surgery
      in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two
      tumors were excised at repeat surgery because of persistent hypercortisolism
      within 14 d of negative exploration of the adenohypophysis. There were no long
      term complications. At follow-up of 71.9 +/- 34.2 months (range, 30-138 months),
      all patients are in remission of CD. Adult patients have had significant
      improvement in weight and body mass indices, with restoration of normal menses in
      all women. In the four pediatric patients, height, weight, and body mass indices
      have been restored toward normal by surgical remission of CD. Hypopituitarism or
      long-term neurohypophysial dysfunction has not occurred. CONCLUSION: We report a
      new subset of patients with CD, ACTH-secreting adenomas that arise wholly within
      the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is
      not identified in the adenohypophysis and in patients with persistent
      hypercortisolism after complete or partial excision of the anterior lobe, tumor
      within the neurohypophysis should be considered; selective adenomectomy of a
      neurohypophyseal, ACTH-secreting tumor can produce long-term remission.

PMID- 16636118
TI  - Change in cortical bone density and its distribution differs between boys and
      girls during puberty.
AB  - CONCEPT: Postmenarchal girls and premenopausal women have 3-4% higher cortical
      bone density (CoD, milligrams per cubic centimeter), compared with postpubertal
      boys and men, respectively. Females' denser cortical bone is thought to serve as
      a calcium reservoir for reproductive needs. However, prospective data are lacking
      that describe CoD development and bone mineral density distribution during
      puberty in both sexes. OBJECTIVE: Thus, our objectives were to assess maturity
      and sex differences in the 20-month change of CoD and radial distribution of bone
      mineral density (RDBMD, milligrams per cubic centimeter) in early-, peri-, and
      postpubertal girls and boys. Maturity groups were based on change in menarcheal
      status (girls, n = 68) and pubic hair stage (Tanner) (boys, n = 59). Peripheral
      quantitative computed tomography was used to measure CoD and RDBMD at the tibial
      middiaphysis. RESULTS: The increase in average CoD was 1.9% [22.8 mg/cm(3); 95%
      confidence interval (CI), 10-36], 2.8% (33.8 mg/cm(3); 95% CI, 21-47), and 1.5%
      (55.0 mg/cm(3); 95% CI, 17-93) greater in early, peri-, and postpubertal girls,
      compared with boys, respectively. Analysis of RDBMD revealed that the change in
      density distribution varied across pubertal groups in girls. Across puberty, all
      girls showed an increase in the high density midcortical region, whereas only
      peripubertal girls showed an increase in the lower density subcortical region. A
      sex-difference in RDBMD change was noted within early and peripubertal groups.
      CONCLUSIONS: Our findings of sexual dimorphism in CoD development give support to
      the hypothesis that female bone deposits calcium for reproductive needs by
      consolidation of cortical bone during puberty.

PMID- 16636119
TI  - Interleukin-1 system gene polymorphisms are associated with fat mass in young
      men.
AB  - CONTEXT: There is growing evidence for interactions between the regulation of
      body fat and the immune system. Studies of knockout mice indicate that IL-1 has
      an antiobesity effect. OBJECTIVE: The objective of the study was to investigate
      our hypothesis that common polymorphisms of the IL-1 system, which are associated
      with IL-1 activity, also are associated with fat mass. DESIGN, SETTING, AND STUDY
      SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a
      population-based cross-sectional study of 18- to 20-yr-old men (n = 1068), mostly
      Caucasian, from the Gothenburg area (Sweden). Three different polymorphisms, IL
      1beta +3953 C/T, IL-1beta-31 T/C, and IL-1 receptor antagonist (IL-1RN) variable
      number tandem repeat of 86 bp, were investigated in relation to body fat mass.
      MAIN OUTCOME MEASURE: The main outcome measures were genotype distributions and
      their association with body fat mass in different compartments, measured with
      dual-energy x-ray absorptiometry. RESULTS: Carriers of the T variant (CT and TT)
      of the +3953 C to T (F(T) = 0.25) IL-1beta gene polymorphism had significantly
      lower total fat mass (P = 0.013) and also significantly reduced arm, leg, and
      trunk fat, compared with CC individuals. IL-1RN*2 carriers with two repeats of
      the IL-1RN variable number tandem repeat polymorphism had increased total fat (P
      = 0.036), serum leptin, and fat of trunk and arm as well as serum levels of IL
      1RN and IL-1RN production ex vivo. The IL-1beta-31 polymorphism did not correlate
      with the fat measurements. CONCLUSIONS: The IL-1 system, recently shown to affect
      fat mass in experimental animals, contains gene polymorphisms that are associated
      with fat mass in young men.

PMID- 16636120
TI  - Comparison of weekly treatment of postmenopausal osteoporosis with alendronate
      versus risedronate over two years.
AB  - OBJECTIVE: A 1-yr extension of the Fosamax Actonel Comparison Trial was completed
      to compare changes in bone mineral density (BMD), bone turnover, and upper
      gastrointestinal tolerability over 2 yr of treatment. DESIGN: This was a
      randomized, double-blind extension conducted at 72 U.S. sites. PATIENTS AND
      METHODS: Of the 1053 women who completed yr 1, 833 postmenopausal women with low
      BMD entered the extension, continuing their same treatment allocation [once
      weekly (OW) alendronate 70 mg or OW risedronate 35 mg]. Changes in BMD at the hip
      trochanter, total hip, femoral neck, and lumbar spine and in markers of bone
      turnover were compared at 24 months. Tolerability was assessed by adverse
      experience reporting. RESULTS: Alendronate produced greater increases from
      baseline in BMD at 24 months than did risedronate at the trochanter (alendronate,
      4.6%; risedronate, 2.5%, P < 0.001) as well as at all other BMD sites.
      Significantly more alendronate than risedronate patients had measured BMD
      increases of 0% or more and 3% or more at all BMD sites (P < 0.001), and fewer
      alendronate patients had measured decreases of 3% or more at all BMD sites.
      Significantly greater reductions in all biochemical markers of bone turnover
      occurred with alendronate, compared with risedronate. No differences were seen in
      occurrence or discontinuations due to upper gastrointestinal adverse experiences.
      CONCLUSIONS: Patients receiving 70 mg OW alendronate had greater gains in BMD,
      were more likely to maintain or gain BMD, and had greater reductions in bone
      turnover markers than patients receiving 35 mg OW risedronate after 24 months,
      with no differences in upper gastrointestinal tolerability.

PMID- 16636121
TI  - Thyroid hormones, dementia, and atrophy of the medial temporal lobe.
AB  - CONTEXT: Thyroid function has been related to Alzheimer disease (AD), but it
      remains unclear whether thyroid dysfunction results from or contributes to
      developing AD. OBJECTIVE: The objective of the study was to determine the
      association between thyroid function and both medial temporal lobe atrophy on
      brain magnetic resonance imaging (MRI) as putative early sign of AD and risk of
      dementia. DESIGN AND PARTICIPANTS: This was a population-based cohort study among
      1077 elderly subjects aged 60-90 yr and dementia free at baseline (1995-1996).
      MAIN OUTCOME MEASURES: Nonfasting serum levels of TSH, free T(4) (fT(4)), T(3),
      and rT(3) were available in 1025 subjects followed up for incident dementia until
      2005. In a subset of 489 nondemented elderly, we assessed volumes of the
      hippocampus and amygdala on brain MRI. Subjects using thyroid medication were
      excluded. RESULTS: During 5657 person-years of follow-up (mean 5.5 yr), 63
      subjects were diagnosed with dementia (46 with AD). TSH and thyroid hormones were
      not associated with risk of dementia or AD. TSH and T(3) were also not related to
      brain atrophy, whereas nondemented subjects with higher fT(4) levels had more
      hippocampal and amygdalar atrophy on MRI. Similar associations were found for
      rT(3). Excluding subjects with thyroid disorders or incipient AD did not change
      the results. CONCLUSION: In our study, TSH was related neither to risk of AD nor
      with early MRI markers thereof, arguing against an important role of thyroid
      function in the development of AD. Whether the association of higher fT(4) and
      rT(3) levels with brain atrophy on MRI has functional significance remains to be
      elucidated.

PMID- 16636122
TI  - Activating mutations in the gene encoding Kir6.2 alter fetal and postnatal growth
      and also cause neonatal diabetes.
AB  - CONTEXT: Birth weight is a bioassay for fetal insulin secretion because altered
      insulin secretion in utero alters insulin-mediated growth. Activating mutations
      in Kir6.2 are the major cause of neonatal diabetes and reduce insulin secretion
      by altering the closure of the beta-cell ATP-sensitive potassium channel in the
      presence of ATP. OBJECTIVE: Our objective was to examine fetal and postnatal
      growth in patients with activating Kir6.2 mutations and identify whether this was
      modified by severity of mutation or maternal diabetes. PATIENTS AND METHODS: We
      used sd scores (SDS) for birth and postnatal growth in an international series of
      patients (n = 49) with Kir6.2 mutations and related this to their clinical
      phenotype. RESULTS: Birth weight was greatly reduced [-1.73 (-3.68 to 1.41),
      median (range) SDS], but there was postnatal catch-up because present weight was
      normal [-0.37 (-4.37 to 2.34) SDS]. Catch-up growth for height and weight was not
      seen until insulin treatment was started. Birth weight was not influenced by
      severity of postnatal phenotype but was increased by maternal diabetes -0.12 vs. 
      1.81 SDS (P = 0.037). Patients with the severe neurological developmental delay,
      epilepsy, and neonatal diabetes syndrome did not catch up (present weight -2.2
      vs. -0.24 SDS (P = 0.003). CONCLUSIONS: Kir6.2 mutations greatly reduce fetal
      insulin secretion and hence fetal growth, but this is independent of mutation
      severity. Increased fetal growth in response to maternal diabetes suggests that
      either the Kir6.2 mutated fetal beta-cell is still glucose responsive or there is
      a non-insulin-mediated increase in fetal growth. Postnatal catch-up requires
      insulin treatment but is complete, except in those with epilepsy.

PMID- 16636123
TI  - Effects of six months of daily low-dose perchlorate exposure on thyroid function
      in healthy volunteers.
AB  - CONTEXT: Perchlorate has been detected in U.S. drinking water supplies at levels
      ranging from 4 to 200 microg/liter as well as in agricultural products.
      Perchlorate is known to be a competitive inhibitor of iodine uptake by the
      thyroid through the sodium-iodide symporter. OBJECTIVE: The objective of the
      study was to determine whether prolonged exposure (6 months) to low levels of
      perchlorate would perturb thyroid function. DESIGN: This was a prospective,
      double-blinded, randomized trial. PARTICIPANTS: The study population consisted of
      13 healthy volunteers. INTERVENTION: INTERVENTIONs included placebo vs. 0.5 mg or
      3.0 mg potassium perchlorate daily. MAIN OUTCOME MEASURES: Serum thyroid function
      tests, 24-h radioactive iodine uptake, serum thyroglobulin (Tg), urinary iodine
      and perchlorate, and serum perchlorate were measured. RESULTS: Mean urinary
      perchlorate value during ingestion of 0.5 mg perchlorate daily was 332.7 +/- 66.1
      microg per 24 h or 248.5 +/- 64.5 microg/g creatinine and mean values for the
      four subjects who received 3 mg perchlorate daily were 2079.5 +/- 430.0 microg
      per 24 h or 1941.7 +/- 138.5 microg/g creatinine. There was no significant change
      in the thyroid (123)I uptakes during perchlorate administration. There were no
      significant changes in serum T(3), free T(4) index, TSH, or Tg concentrations
      during the exposure period, compared to baseline or postexposure values. Urine
      iodine values for the 3-mg perchlorate group were higher, but not significantly
      so, at baseline than during perchlorate exposure. CONCLUSIONS: We observed that a
      6-month exposure to perchlorate at doses up to 3 mg/d had no effect on thyroid
      function, including inhibition of thyroid iodide uptake as well as serum levels
      of thyroid hormones, TSH, and Tg.

PMID- 16636124
TI  - Sustained benefits from previous physical activity on bone mineral density in
      males.
AB  - CONTEXT: The effect of physical activity on bone mineral density (BMD) is not
      well investigated longitudinally after puberty in men. OBJECTIVE: Our objective
      was to evaluate the effect of exercise and reduced exercise on BMD after puberty
      in men. DESIGN: We conducted a longitudinal study. PARTICIPANTS: Sixty-three
      healthy young athletes and 27 male controls, both with a mean age of 17 yr at
      baseline, participated. Also, 136 of the participants' parents were investigated
      to evaluate heritable influences. MAIN OUTCOME MEASURES: Total body, total hip,
      femoral neck, and humerus BMD (grams per square centimeter) were measured at
      baseline and after mean periods of 27, 68, and 94 months in the young cohort.
      RESULTS: BMDs of control parents and athlete parents were equal, suggesting
      absence of selection bias. The 23 athletes that remained active throughout the
      study increased BMD at all sites when compared with controls (mean difference,
      0.04-0.12 g/cm(2); P < 0.05) during the study period. After an average of 3 yr,
      27 athletes ended their active careers. Although this group initially lost BMD at
      the hip compared with active athletes, the former athletes still had higher BMD
      than controls at the femoral neck (0.12 g/cm(2); P = 0.007), total hip (0.11
      g/cm(2); P = 0.02), and humerus (0.10 g/cm(2); P = 0.02) at the final follow-up.
      CONCLUSIONS: High sensitivity to physical loading persists after puberty in men.
      Reduced physical activity is associated with BMD loss in the first 3 yr in weight
      bearing bone. Sustained benefits in BMD are preserved 5 yr after intensive
      training ends.

PMID- 16636125
TI  - Genetic variation in the visfatin gene (PBEF1) and its relation to glucose
      metabolism and fat-depot-specific messenger ribonucleic acid expression in
      humans.
AB  - CONTEXT AND OBJECTIVE: Visfatin is a peptide suggested to play a role in glucose
      homeostasis. In the present study, we investigated the role of genetic variation
      in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus
      (T2DM). DESIGN: The visfatin gene (PBEF1) was sequenced in DNA samples from 24
      nonrelated Caucasian subjects. Identified genetic variants were used for
      association analyses of T2DM in a case-control study (503 diabetic subjects and
      476 healthy controls) and T2DM-related traits in 626 nondiabetic subjects. The
      effect of genetic variation in the visfatin gene on its mRNA expression in a
      subgroup of 157 nondiabetic subjects with measurements of visfatin mRNA
      expression in visceral and sc fat depots was also analyzed. RESULTS: Seven single
      nucleotide polymorphisms (SNPs) and one insertion/deletion were identified. Three
      SNPs (rs9770242, -948G-->T, rs4730153) that were representatives of their linkage
      disequilibrium groups were genotyped in Caucasians from Germany with a wide range
      of body fat distribution and insulin sensitivity for association analyses. No
      association of T2DM with any of the genotyped SNPs or their haplotypes was found.
      However, the ratio of visceral/sc visfatin mRNA expression was associated with
      all three genetic polymorphisms (P < 0.05). Moreover, the -948G-->T variant was
      associated with 2-h plasma glucose and fasting insulin concentrations (P < 0.05)
      in nondiabetic subjects. CONCLUSIONS: In conclusion, our data suggest that
      genetic variation in the visfatin gene may have a minor effect on visceral and sc
      visfatin mRNA expression profiles but does not play a major role in the
      development of obesity or T2DM.

PMID- 16636126
TI  - Epigenetic modification of the X chromosome influences susceptibility to
      polycystic ovary syndrome.
AB  - CONTEXT: The cause of polycystic ovary syndrome (PCOS) is unknown, although
      genetic and environmental influences are clearly implicated. Some genetic studies
      have suggested the involvement of X-linked genes in PCOS, but the influence of X
      chromosome inactivation (XCI) on manifestation of this disorder has not
      previously been examined. OBJECTIVE: The objective of the study was to test the
      null hypothesis that XCI has no influence on clinical presentation of PCOS.
      DESIGN: We examined patterns of XCI between sister pairs with the same genotype
      at a polymorphic locus on the X chromosome in families with PCOS. SETTING: The
      study was conducted at a private practice. PARTICIPANTS: PCOS was defined as
      hyperandrogenemia with chronic anovulation. Forty families were studied in which
      DNA was obtained from at least one parent, the proband, and one sister that could
      be accurately diagnosed as being affected or unaffected. MAIN OUTCOME MEASURE(S):
      Relative expression of two X-linked alleles was determined, and the ratio of one
      to the other represented the pattern of XCI. RESULTS: The statistical odds on a
      different clinical presentation between sisters was approximately 29 times higher
      in sister pairs with different patterns of XCI, compared with sister pairs with
      the same pattern of XCI (odds ratio 28.9; 95% confidence interval 4.0-206; P =
      0.0008). CONCLUSIONS: This study provides evidence to refute the null hypothesis
      and propose a closer inspection of X-linked genes in PCOS, one in which both
      genotype and epigenotype are considered. Environmental determinants of PCOS may
      alter clinical presentation via epigenetic modifications, which currently remain
      undetected in traditional genetic analyses.

PMID- 16636127
TI  - Overrepresentation of the N363S variant of the glucocorticoid receptor gene in
      patients with bilateral adrenal incidentalomas.
AB  - CONTEXT: Some variants of the glucocorticoid receptor (GR) gene have been found
      to alter glucocorticoid sensitivity and have been associated with altered
      metabolic profiles. OBJECTIVE: The objective of the study was to examine whether
      N363S and ER22/23K variants of the GR gene may be associated with the development
      of adrenal incidentalomas and whether these variants may contribute to metabolic
      abnormalities frequently present in these patients. DESIGN, SETTING, AND
      PATIENTS: The study included 99 patients with unilateral and 44 patients with
      bilateral adrenal incidentalomas, 102 population-matched control subjects, and
      100 patients with type 2 diabetes mellitus. MAIN OUTCOME MEASURES: Metabolic and
      hormonal parameters and GR gene variants were determined. RESULTS: When compared
      with control subjects, the carrier frequency for the N363S variant was markedly
      and significantly higher in patients with bilateral (7.8 vs. 20.5%, P < 0.05) but
      not in those with unilateral incidentalomas (7.1%) or in patients with type 2
      diabetes (13.0%). Type 2 diabetes occurred more frequently in patients with
      bilateral, compared with those with unilateral incidentalomas (40.9 vs. 22.2%, P
      < 0.05). In patients with bilateral incidentalomas, a significant association of
      the N363S variant with impaired glucose homeostasis but not with body mass index,
      hypertension, hyperlipidemia, or history of coronary artery disease was found.
      The carrier frequency of the ER22/23EK variant was similar in all groups, and
      this variant failed to show any association with metabolic abnormalities.
      CONCLUSION: These results suggest that the N363S variant of the GR gene may play
      a role in the pathogenesis of bilateral adrenal incidentalomas, although the
      mechanism still remains to be investigated.

PMID- 16636128
TI  - A LMNA splicing mutation in two sisters with severe Dunnigan-type familial
      partial lipodystrophy type 2.
AB  - CONTEXT: To date, all cases of familial partial lipodystrophy type 2 (FPLD2;
      Mendelian Inheritance in Man 151660) result from missense mutations in LMNA,
      which encodes nuclear lamin A/C (Mendelian Inheritance in Man 150330). OBJECTIVE:
      The objective of the study was to carry out mutational analysis of LMNA in two
      sisters with a particularly severe FPLD2 phenotype. DESIGN: This was a
      descriptive case report with molecular studies. SETTING: The study was conducted
      at a referral center. PATIENTS: We report two sisters of South Asian origin. The
      first presented with acanthosis nigricans at age 5 yr, diabetes with insulin
      resistance, hypertension and hypertriglyceridemia at age 13 yr, and partial
      lipodystrophy starting at puberty. Her sister and their mother had a similar
      metabolic profile and physical features, and their mother died of vascular
      disease at age 32 yr. INTERVENTIONS: There were no interventions. MAIN OUTCOME
      MEASURES AND RESULTS: LMNA sequencing showed that the sisters were each
      heterozygous for a novel G>C mutation at the intron 8 consensus splice donor
      site, which was absent from the genomes of 300 healthy individuals. The retention
      of intron 8 in mRNA predicted a prematurely truncated lamin A isoform (516
      instead of 664 amino acids) with 20 nonsense 3'-terminal residues. The mutant
      lamin A isoform failed to interact normally with emerin and failed to localize to
      the nuclear envelope. CONCLUSIONS: This is the first LMNA splicing mutation to be
      associated with FPLD2, and it causes a severe clinical and metabolic phenotype.

PMID- 16636129
TI  - Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society
      Clinical Practice Guideline.
AB  - OBJECTIVE: The objective is to provide guidelines for the evaluation and
      treatment of adults with GH deficiency (GHD). PARTICIPANTS: The chair of the Task
      Force was selected by the Clinical Guidelines Subcommittee of The Endocrine
      Society (TES). The chair selected five other endocrinologists and a medical
      writer, who were approved by the Council. One closed meeting of the group was
      held. There was no corporate funding, and members of the group received no
      remuneration. EVIDENCE: Only fully published, peer-reviewed literature was
      reviewed. The Grades of Evidence used are outlined in the Appendix. CONSENSUS
      PROCESS: Consensus was achieved through one group meeting and e-mailing of drafts
      that were written by the group with grammatical/style help from the medical
      writer. Drafts were reviewed successively by the Clinical Guidelines
      Subcommittee, the Clinical Affairs Committee, and TES Council, and a version was
      placed on the TES web site for comments. At each level, the writing group
      incorporated needed changes. CONCLUSIONS: GHD can persist from childhood or be
      newly acquired. Confirmation through stimulation testing is usually required
      unless there is a proven genetic/structural lesion persistent from childhood. GH
      therapy offers benefits in body composition, exercise capacity, skeletal
      integrity, and quality of life measures and is most likely to benefit those
      patients who have more severe GHD. The risks of GH treatment are low. GH dosing
      regimens should be individualized. The final decision to treat adults with GHD
      requires thoughtful clinical judgment with a careful evaluation of the benefits
      and risks specific to the individual.

PMID- 16636130
TI  - Recombinant methionyl human leptin therapy in replacement doses improves insulin
      resistance and metabolic profile in patients with lipoatrophy and metabolic
      syndrome induced by the highly active antiretroviral therapy.
AB  - CONTEXT: Highly active antiretroviral therapy (HAART) for HIV-1 infection has
      been associated with a metabolic syndrome characterized by insulin resistance,
      hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of
      patients with predominant lipoatrophy has low levels of the adipocyte-secreted
      hormone leptin. OBJECTIVE: The objective of the study was to assess whether
      administration of recombinant methionyl human leptin (r-metHuLeptin) improves
      insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient
      subjects with HAART-induced lipoatrophy. DESIGN, SETTING, PATIENTS, AND
      INTERVENTION: We conducted a randomized, placebo-controlled, double-blinded,
      crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced
      lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level
      greater than 300 mg/dl, who were administered placebo for 2 months before or
      after administration of r-metHuLeptin at physiological doses for an additional 2
      months. MAIN OUTCOME MEASURES: Insulin resistance, lipid levels, inflammatory
      markers, body composition, and HIV control were measured. RESULTS: Compared with
      placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin
      resistance (as expressed by the homeostasis model assessment index and an insulin
      suppression test), and high-density lipoprotein. Body weight and fat mass
      decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not
      peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV
      control was not adversely affected. CONCLUSIONS: r-metHuLeptin replacement at
      physiological doses in HIV+ leptin-deficient patients with HAART-induced
      lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal
      fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy,
      including patients with more severe metabolic abnormalities, are warranted to
      evaluate the physiological and potentially therapeutic role of r-metHuLeptin for
      this condition and to fully clarify the underlying mechanisms of action.

PMID- 16636131
TI  - NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and
      pathogenetically models human primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disease with a strong genetic
      component characterized by biliary ductular inflammation with eventual liver
      cirrhosis. The serologic hallmark of PBC is antimitochondrial antibodies that
      react with the pyruvate dehydrogenase complex, targeting the inner lipoyl domain
      of the E2 subunit (anti-PDC-E2). Herein we demonstrate that NOD.c3c4 mice
      congenically derived from the nonobese diabetic strain develop an autoimmune
      biliary disease (ABD) that models human PBC. NOD.c3c4 (at 9-10 wk, before
      significant biliary pathology) develop antibodies to PDC-E2 that are specific for
      the inner lipoyl domain. Affected areas of biliary epithelium are infiltrated
      with CD3+, CD4+, and CD8+ T cells, and treatment of NOD.c3c4 mice with monoclonal
      antibody to CD3 protects from ABD. Furthermore, NOD.c3c4-scid mice develop
      disease after adoptive transfer of splenocytes or CD4+ T cells, demonstrating a
      central role for T cells in pathogenesis. Histological analysis reveals
      destructive cholangitis, granuloma formation, and eosinophilic infiltration as
      seen in PBC, although, unlike PBC, the extrahepatic biliary ducts are also
      affected. Using a congenic mapping approach, we define the first ABD (Abd) locus,
      Abd1. These results identify the NOD.c3c4 mouse as the first spontaneous mouse
      model of PBC.

PMID- 16636132
TI  - Human mesenchymal stem cells exert potent antitumorigenic effects in a model of
      Kaposi's sarcoma.
AB  - Emerging evidence suggests that both human stem cells and mature stromal cells
      can play an important role in the development and growth of human malignancies.
      In contrast to these tumor-promoting properties, we observed that in an in vivo
      model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal
      stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor
      growth. We further show that human MSCs can inhibit the in vitro activation of
      the Akt protein kinase within some but not all tumor and primary cell lines. The
      inhibition of Akt activity requires the MSCs to make direct cell-cell contact and
      can be inhibited by a neutralizing antibody against E-cadherin. We further
      demonstrate that in vivo, Akt activation within KS cells is potently down
      regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor
      suppressive effects of MSCs correlates with their ability to inhibit target cell
      Akt activity, and KS tumors engineered to express a constitutively activated Akt
      construct are no longer sensitive to i.v. MSC administration. These results
      suggest that in contrast to other stem cells or normal stromal cells, MSCs
      possess intrinsic antineoplastic properties and that this stem cell population
      might be of particular utility for treating those human malignancies
      characterized by dysregulated Akt.

PMID- 16636133
TI  - A critical role for the host mediator macrophage migration inhibitory factor in
      the pathogenesis of malarial anemia.
AB  - The pathogenesis of malarial anemia is multifactorial, and the mechanisms
      responsible for its high mortality are poorly understood. Studies indicate that
      host mediators produced during malaria infection may suppress erythroid
      progenitor development (Miller, K.L., J.C. Schooley, K.L. Smith, B. Kullgren,
      L.J. Mahlmann, and P.H. Silverman. 1989. Exp. Hematol. 17:379-385; Yap, G.S., and
      M.M. Stevenson. 1991. Ann. NY Acad. Sci. 628:279-281). We describe an intrinsic
      role for macrophage migration inhibitory factor (MIF) in the development of the
      anemic complications and bone marrow suppression that are associated with malaria
      infection. At concentrations found in the circulation of malaria-infected
      patients, MIF suppressed erythropoietin-dependent erythroid colony formation. MIF
      synergized with tumor necrosis factor and gamma interferon, which are known
      antagonists of hematopoiesis, even when these cytokines were present in
      subinhibitory concentrations. MIF inhibited erythroid differentiation and
      hemoglobin production, and it antagonized the pattern of mitogen-activated
      protein kinase phosphorylation that normally occurs during erythroid progenitor
      differentiation. Infection of MIF knockout mice with Plasmodium chabaudi resulted
      in less severe anemia, improved erythroid progenitor development, and increased
      survival compared with wild-type controls. We also found that human mononuclear
      cells carrying highly expressed MIF alleles produced more MIF when stimulated
      with the malarial product hemozoin compared with cells carrying low expression
      MIF alleles. These data suggest that polymorphisms at the MIF locus may influence
      the levels of MIF produced in the innate response to malaria infection and the
      likelihood of anemic complications.

PMID- 16636134
TI  - Toll-like receptor agonists influence the magnitude and quality of memory T cell
      responses after prime-boost immunization in nonhuman primates.
AB  - There is a remarkable heterogeneity in the functional profile (quality) of T cell
      responses. Importantly, the magnitude and/or quality of a response required for
      protection may be different depending on the infection. Here, we assessed the
      capacity of different Toll like receptor (TLR)-binding compounds to influence T
      helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman
      primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag
      protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a
      TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine
      oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication
      defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV
      Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of
      Th1 responses after primary immunization compared to all other vaccine groups.
      Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine
      responses, there was a striking increase in HIV Gag-specific CD8+ T cell
      responses after the boost in all animals that had received a primary immunization
      with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant
      used during primary immunization conferred stability and dramatically influenced
      the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag
      boost. These data provide insights for designing prime-boost immunization
      regimens to optimize Th1 and CD8+ T cell responses.

PMID- 16636135
TI  - Radiation modulates the peptide repertoire, enhances MHC class I expression, and
      induces successful antitumor immunotherapy.
AB  - Radiotherapy is one of the most successful cancer therapies. Here the effect of
      irradiation on antigen presentation by MHC class I molecules was studied. Cell
      surface expression of MHC class I molecules was increased for many days in a
      radiation dose-dependent manner as a consequence of three responses. Initially,
      enhanced degradation of existing proteins occurred which resulted in an increased
      intracellular peptide pool. Subsequently, enhanced translation due to activation
      of the mammalian target of rapamycin pathway resulted in increased peptide
      production, antigen presentation, as well as cytotoxic T lymphocyte recognition
      of irradiated cells. In addition, novel proteins were made in response to gamma
      irradiation, resulting in new peptides presented by MHC class I molecules, which
      were recognized by cytotoxic T cells. We show that immunotherapy is successful in
      eradicating a murine colon adenocarcinoma only when preceded by radiotherapy of
      the tumor tissue. Our findings indicate that directed radiotherapy can improve
      the efficacy of tumor immunotherapy.

PMID- 16636136
TI  - Sustained aryl hydrocarbon receptor activity attenuates liver regeneration.
AB  - In hepatocyte-derived cell lines, either loss of aryl hydrocarbon receptor (AhR)
      function or treatment with a persistent AhR agonist such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) can disrupt G1 phase cell cycle progression.
      The present study used liver regeneration to explore mechanistically how AhR
      activity modulates hepatocyte proliferation in vivo. Treatment of mice with 20
      mug/kg TCDD 1 day before 70% partial hepatectomy (PH) resulted in a 50 to 75%
      suppression in liver regeneration. Impaired proliferation was not associated with
      changes in levels of interleukin-6 or tumor necrosis factor-alpha, which prime
      quiescent hepatocytes to enter G1 phase. In fact, administration of TCDD 12 h
      after PH, a period well beyond the priming phase, still induced the G1 arrest.
      Decreased proliferation in TCDD-treated mice correlated with reduced cyclin
      dependent kinase-2 (CDK2) activity, a pivotal regulator of G1/S phase transition.
      In contrast to observations made in cell culture, suppressed CDK2 activity was
      not strictly associated with increased binding of the CDK2 inhibitors p21Cip1 or
      p27Kip1. However, TCDD decreased levels of cyclin E binding to CDK2, despite
      normal cyclin E expression. The evidence also suggests that TCDD-induced hepatic
      growth arrest depends upon sustained AhR activity because transient AhR
      activation in response to endogenous queues failed to suppress the regenerative
      response. These findings establish a functional role for the AhR in regulating
      normal cell cycle control during liver regeneration.

PMID- 16636137
TI  - A boronic-chalcone derivative exhibits potent anticancer activity through
      inhibition of the proteasome.
AB  - Chalcones and their derivatives have been shown to have potent anticancer
      activity. However, the exact mechanisms of cytotoxic activity remain to be
      established. In this study, we have evaluated a series of boronic chalcones for
      their anticancer activity and mechanisms of action. Among the eight chalcone
      derivatives tested, 3,5-bis-(4-boronic acid-benzylidene)-1-methyl-piperidin-4-one
      (AM114) exhibited most potent growth inhibitory activity with IC50 values of 1.5
      and 0.6 microM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay and colony formation assay, respectively. The cytotoxic activity of AM114
      was shown to be associated with the accumulation of p53 and p21 proteins and
      induction of apoptosis. Mechanistic studies showed that AM114 treatment inhibited
      the chymotrypsin-like activity of the 20S proteasome in vitro, leading to a
      significant accumulation of ubiquitinated p53 and other cellular proteins in
      whole cells. In vitro studies showed that AM114 did not significantly disrupt the
      interaction of p53 and murine double minute 2 protein. It is noteworthy that
      AM114 as a single agent was preferentially toxic to cells with wild-type p53
      expression, whereas combination of this compound with ionizing radiation (IR)
      significantly enhanced the cell-killing activity of IR in both wild-type p53 and
      p53-null cells. Together, these results indicate that the boronic chalcone
      derivative AM114 induces significant cytotoxic effect in cancer cells through the
      inhibition of the cellular proteasome and provide a rationale for the further
      development of this class of compounds as novel cancer chemotherapeutic agents.

PMID- 16636138
TI  - Parametric regression on cumulative incidence function.
AB  - We propose parametric regression analysis of cumulative incidence function with
      competing risks data. A simple form of Gompertz distribution is used for the
      improper baseline subdistribution of the event of interest. Maximum likelihood
      inferences on regression parameters and associated cumulative incidence function
      are developed for parametric models, including a flexible generalized odds rate
      model. Estimation of the long-term proportion of patients with cause-specific
      events is straightforward in the parametric setting. Simple goodness-of-fit tests
      are discussed for evaluating a fixed odds rate assumption. The parametric
      regression methods are compared with an existing semiparametric regression
      analysis on a breast cancer data set where the cumulative incidence of recurrence
      is of interest. The results demonstrate that the likelihood-based parametric
      analyses for the cumulative incidence function are a practically useful
      alternative to the semiparametric analyses.

PMID- 16636139
TI  - Quantile regression for longitudinal data using the asymmetric Laplace
      distribution.
AB  - In longitudinal studies, measurements of the same individuals are taken
      repeatedly through time. Often, the primary goal is to characterize the change in
      response over time and the factors that influence change. Factors can affect not
      only the location but also more generally the shape of the distribution of the
      response over time. To make inference about the shape of a population
      distribution, the widely popular mixed-effects regression, for example, would be
      inadequate, if the distribution is not approximately Gaussian. We propose a novel
      linear model for quantile regression (QR) that includes random effects in order
      to account for the dependence between serial observations on the same subject.
      The notion of QR is synonymous with robust analysis of the conditional
      distribution of the response variable. We present a likelihood-based approach to
      the estimation of the regression quantiles that uses the asymmetric Laplace
      density. In a simulation study, the proposed method had an advantage in terms of
      mean squared error of the QR estimator, when compared with the approach that
      considers penalized fixed effects. Following our strategy, a nearly optimal
      degree of shrinkage of the individual effects is automatically selected by the
      data and their likelihood. Also, our model appears to be a robust alternative to
      the mean regression with random effects when the location parameter of the
      conditional distribution of the response is of interest. We apply our model to a
      real data set which consists of self-reported amount of labor pain measurements
      taken on women repeatedly over time, whose distribution is characterized by
      skewness, and the significance of the parameters is evaluated by the likelihood
      ratio statistic.

PMID- 16636140
TI  - A new approach to intensity-dependent normalization of two-channel microarrays.
AB  - A two-channel microarray measures the relative expression levels of thousands of
      genes from a pair of biological samples. In order to reliably compare gene
      expression levels between and within arrays, it is necessary to remove systematic
      errors that distort the biological signal of interest. The standard for
      accomplishing this is smoothing "MA-plots" to remove intensity-dependent dye bias
      and array-specific effects. However, MA methods require strong assumptions, which
      limit their general applicability. We review these assumptions and derive several
      practical scenarios in which they fail. The "dye-swap" normalization method has
      been much less frequently used because it requires two arrays per pair of
      samples. We show that a dye-swap is accurate under general assumptions, even
      under intensity-dependent dye bias, and that a dye-swap removes dye bias from a
      single pair of samples in general. Based on a flexible model of the relationship
      between mRNA amount and single-channel fluorescence intensity, we demonstrate the
      general applicability of a dye-swap approach. We then propose a common array dye
      swap (CADS) method for the normalization of two-channel microarrays. We show that
      CADS removes both dye bias and array-specific effects, and preserves the true
      differential expression signal for every gene under the assumptions of the model.

PMID- 16636141
TI  - Structural activation of Mad2 in the mitotic spindle checkpoint: the two-state
      Mad2 model versus the Mad2 template model.
AB  - The inheritance of a normal assortment of chromosomes during each cell division
      relies on a cell-cycle surveillance system called the mitotic spindle checkpoint.
      The existence of sister chromatids that do not achieve proper bipolar attachment
      to the mitotic spindle in a cell activates this checkpoint, which inhibits the
      ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C)
      and delays the onset of anaphase. The mitotic arrest deficiency 2 (Mad2) spindle
      checkpoint protein inhibits APC/C through binding to its mitotic-specific
      activator, Cdc20. Binding of Mad2 to Cdc20 involves a large conformational change
      of Mad2 and requires the Mad1-Mad2 interaction in vivo. Two related but distinct
      models of Mad1-assisted activation of Mad2, the "two-state Mad2" and the "Mad2
      template" models, have been proposed. I review the recent structural,
      biochemical, and cell biological data on Mad2, discuss the differences between
      the two models, and propose experiments that test their key principles.

PMID- 16636142
TI  - CAR-1 and trailer hitch: driving mRNP granule function at the ER?
AB  - The targeting of messenger RNAs (mRNAs) to specific subcellular sites for local
      translation plays an important role in diverse cellular and developmental
      processes in eukaryotes, including axis formation, cell fate determination,
      spindle pole regulation, cell motility, and neuronal synaptic plasticity.
      Recently, a new conserved class of Lsm proteins, the Scd6 family, has been
      implicated in controlling mRNA function. Depletion or mutation of members of the
      Scd6 family, Caenorhabditis elegans CAR-1 and Drosophila melanogaster trailer
      hitch, lead to a variety of developmental phenotypes, which in some cases can be
      linked to alterations in the endoplasmic reticulum (ER). Scd6/Lsm proteins are
      RNA binding proteins and are found in RNP complexes associated with translational
      control of mRNAs, and these complexes can colocalize with the ER. These findings
      raise the possibility that localization and translational regulation of mRNAs at
      the ER plays a role in controlling the organization of this organelle.

PMID- 16636143
TI  - Kinesin 5-independent poleward flux of kinetochore microtubules in PtK1 cells.
AB  - Forces in the spindle that align and segregate chromosomes produce a steady
      poleward flux of kinetochore microtubules (MTs [kMTs]) in higher eukaryotes. In
      several nonmammalian systems, flux is driven by the tetrameric kinesin Eg5
      (kinesin 5), which slides antiparallel MTs toward their minus ends. However, we
      find that the inhibition of kinesin 5 in mammalian cultured cells (PtK1) results
      in only minor reduction in the rate of kMT flux from approximately 0.7 to
      approximately 0.5 microm/min, the same rate measured in monopolar spindles that
      lack antiparallel MTs. These data reveal that the majority of poleward flux of
      kMTs in these cells is not driven by Eg5. Instead, we favor a polar "pulling-in"
      mechanism in which a depolymerase localized at kinetochore fiber minus ends makes
      a major contribution to poleward flux. One candidate, Kif2a (kinesin 13), was
      detected at minus ends of fluxing kinetochore fibers. Kif2a remains associated
      with the ends of K fibers upon disruption of the spindle by dynein/dynactin
      inhibition, and these K fibers flux.

PMID- 16636144
TI  - The secretory membrane system in the Drosophila syncytial blastoderm embryo
      exists as functionally compartmentalized units around individual nuclei.
AB  - Drosophila melanogaster embryogenesis begins with 13 nuclear division cycles
      within a syncytium. This produces >6,000 nuclei that, during the next division
      cycle, become encased in plasma membrane in the process known as cellularization.
      In this study, we investigate how the secretory membrane system becomes equally
      apportioned among the thousands of syncytial nuclei in preparation for
      cellularization. Upon nuclear arrival at the cortex, the endoplasmic reticulum
      (ER) and Golgi were found to segregate among nuclei, with each nucleus becoming
      surrounded by a single ER/Golgi membrane system separate from adjacent ones. The
      nuclear-associated units of ER and Golgi across the syncytial blastoderm produced
      secretory products that were delivered to the plasma membrane in a spatially
      restricted fashion across the embryo. This occurred in the absence of plasma
      membrane boundaries between nuclei and was dependent on centrosome-derived
      microtubules. The emergence of secretory membranes that compartmentalized around
      individual nuclei in the syncytial blastoderm is likely to ensure that secretory
      organelles are equivalently partitioned among nuclei at cellularization and could
      play an important role in the establishment of localized gene and protein
      expression patterns within the early embryo.

PMID- 16636145
TI  - Lysosomal biogenesis and function is critical for necrotic cell death in
      Caenorhabditis elegans.
AB  - Necrotic cell death is defined by distinctive morphological characteristics that
      are displayed by dying cells (Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F.
      Kerr. 1988. Methods Achiev. Exp. Pathol. 13:18-54). The cellular events that
      transpire during necrosis to generate these necrotic traits are poorly
      understood. Recent studies in the nematode Caenorhabditis elegans show that
      cytoplasmic acidification develops during necrosis and is required for cell death
      (Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249-1254).
      However, the origin of cytoplasmic acidification remains elusive. We show that
      the alkalization of endosomal and lysosomal compartments ameliorates necrotic
      cell death triggered by diverse stimuli. In addition, mutations in genes that
      result in altered lysosomal biogenesis and function markedly affect neuronal
      necrosis. We used a genetically encoded fluorescent marker to follow lysosome
      fate during neurodegeneration in vivo. Strikingly, we found that lysosomes fuse
      and localize exclusively around a swollen nucleus. In the advanced stages of cell
      death, the nucleus condenses and migrates toward the periphery of the cell,
      whereas green fluorescent protein-labeled lysosomal membranes fade, indicating
      lysosomal rupture. Our findings demonstrate a prominent role for lysosomes in
      cellular destruction during necrotic cell death, which is likely conserved in
      metazoans.

PMID- 16636146
TI  - Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and
      represses c-myc transcription.
AB  - Transcriptional control plays a key role in regulating epidermal proliferation
      and differentiation. Although ample information has been obtained on how
      epidermal homeostasis is controlled in adult skin, less is known about the
      control of proliferation/differentiation of epidermal stem/progenitor cells in
      the developing embryo. Ovol1, encoding a zinc finger protein homologous to
      Drosophila melanogaster Ovo, is expressed in embryonic epidermal progenitor cells
      that are transiting from proliferation to terminal differentiation. In this
      study, we demonstrate a function for Ovol1 in interfollicular epidermal
      development. In its absence, developing epidermis fails to properly restrict the
      proliferative potential of progenitor cells, and cultured keratinocytes fail to
      efficiently undergo growth arrest in response to extrinsic growth-inhibitory
      signals. We present molecular evidence that c-myc expression is up-regulated in
      Ovol1-deficient suprabasal cells and that Ovol1 represses c-myc transcription by
      directly binding to its promoter. Collectively, our findings indicate that Ovol1
      is required for proliferation exit of committed epidermal progenitor cells and
      identify c-myc as an Ovol1 target.

PMID- 16636147
TI  - Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane
      partitioning.
AB  - Loss of tuberin, the product of TSC2 gene, increases mammalian target of
      rapamycin (mTOR) signaling, promoting cell growth and tumor development. However,
      in cells expressing tuberin, it is not known how repression of mTOR signaling is
      relieved to activate this pathway in response to growth factors and how hamartin
      participates in this process. We show that hamartin colocalizes with
      hypophosphorylated tuberin at the membrane, where tuberin exerts its GTPase
      activating protein (GAP) activity to repress Rheb signaling. In response to
      growth signals, tuberin is phosphorylated by AKT and translocates to the cytosol,
      relieving Rheb repression. Phosphorylation of tuberin at serines 939 and 981 does
      not alter its intrinsic GAP activity toward Rheb but partitions tuberin to the
      cytosol, where it is bound by 14-3-3 proteins. Thus, tuberin bound by 14-3-3 in
      response to AKT phosphorylation is sequestered away from its membrane-bound
      activation partner (hamartin) and its target GTPase (Rheb) to relieve the growth
      inhibitory effects of this tumor suppressor.

PMID- 16636148
TI  - A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through
      the scaffold protein tamalin.
AB  - Neurotrophins play an essential role in mammalian development. Most of their
      functions have been attributed to activation of the kinase-active Trk receptors
      and the p75 neurotrophin receptor. Truncated Trk receptor isoforms lacking the
      kinase domain are abundantly expressed during development and in the adult;
      however, their function and signaling capacity is largely unknown. We show that
      the neurotrophin-3 (NT3) TrkCT1-truncated receptor binds to the scaffold protein
      tamalin in a ligand-dependent manner. Moreover, NT3 initiation of this complex
      leads to activation of the Rac1 GTPase through adenosine diphosphate-ribosylation
      factor 6 (Arf6). At the cellular level, NT3 binding to TrkCT1-tamalin induces
      Arf6 translocation to the membrane, which in turn causes membrane ruffling and
      the formation of cellular protrusions. Thus, our data identify a new signaling
      pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish
      NT3 as an upstream regulator of Arf6.

PMID- 16636149
TI  - Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: the
      role of sphingosine kinase-1.
AB  - The transactivation of enhanced growth factor receptor (EGFR) by G protein
      coupled receptor (GPCR) ligands is recognized as an important signaling mechanism
      in the regulation of complex biological processes, such as cancer development.
      Estrogen (E2), which is a steroid hormone that is intimately implicated in breast
      cancer, has also been suggested to function via EGFR transactivation. In this
      study, we demonstrate that E2-induced EGFR transactivation in human breast cancer
      cells is driven via a novel signaling system controlled by the lipid kinase
      sphingosine kinase-1 (SphK1). We show that E2 stimulates SphK1 activation and the
      release of sphingosine 1-phosphate (S1P), by which E2 is capable of activating
      the S1P receptor Edg-3, resulting in the EGFR transactivation in a matrix
      metalloprotease-dependent manner. Thus, these findings reveal a key role for
      SphK1 in the coupling of the signals between three membrane-spanning events
      induced by E2, S1P, and EGF. They also suggest a new signal transduction model
      across three individual ligand-receptor systems, i.e., "criss-cross"
      transactivation.

PMID- 16636151
TI  - An introduction to allies against asthma and this special issue.

PMID- 16636152
TI  - Community coalitions to control chronic disease: Allies against asthma as a model
      and case study.
AB  - There is a rich and extensive literature regarding coalitions as vehicles for
      amassing resources, influence, and energy in pursuit of a health goal. Despite
      insufficient empirical data regarding outcome, a number of observers have posited
      the aspects of coalition processes thought to lead to goal attainment. The
      supplement, which this article is part of, is devoted to an examination of how
      these elements fitted together (or did not) in the seven areas across the United
      States where Allies coalitions devoted themselves to achieving asthma control.
      The aim of this article is to present the theoretical bases for the work of the
      coalitions. It illustrates and emphasizes how the community context influenced
      coalition development, how membership was involved in and assessed coalition
      processes and structures, and the community-wide actions that were instituted and
      the capacities they were trying to strengthen.

PMID- 16636153
TI  - Building allies coalitions: Why formation matters.
AB  - This article describes how formation of the Allies Against Asthma coalitions was
      influenced by community context, history, leadership, membership, structure,
      processes, and other factors. Based on member surveys, key informant interviews,
      and self-assessment tools, results indicate that three coalitions developed from
      existing coalitions, and four formed in response to funding. The coalitions took
      an average of 12 months to form and completed 98% of formation tasks. Funding,
      technical support, and networking among grantees promoted formation. Although
      cultures, geographies, lead agencies, and years of experience differed,
      coalitions developed similar structures and processes. Two of three new
      coalitions took the longest to form, highlighting the need for flexibility and
      technical assistance when funding new coalitions.

PMID- 16636154
TI  - From formation to action: How allies against asthma coalitions are getting the
      job done.
AB  - Coalitions develop in and recycle through stages. At each stage (formation,
      implementation, maintenance, and institutionalization), certain factors enhance
      coalition function, accomplishment of tasks, and progression to the next stage.
      The Allies Against Asthma coalitions assessed stages of development through
      annual member surveys, key informant interviews of 16 leaders from each site, and
      other evaluation tools. Results indicate all coalitions completed formation and
      implementation, six achieved maintenance, and five are in the
      institutionalization stage. Differences among coalitions can be attributed to
      their maturity and experience working within a coalition framework. Participants
      agreed that community mobilization around asthma would not have happened without
      coalitions. They attributed success to being responsive to community needs and
      developing comprehensive strategies, and they believed that partners' goals were
      more innovative and achievable than any institution could have created alone.

PMID- 16636155
TI  - Collaborative design and implementation of a multisite community coalition
      evaluation.
AB  - Evaluation designs assessing community coalitions must balance measures of how
      coalitions do their work and evidence that the coalitions are making a
      difference. The Allies cross-site evaluation attempts to determine the combined
      effects of the seven coalitions' work at the individual, organizational, and
      community levels. Principal components considered are (a) contextual factors of
      the coalition community, (b) coalition processes and structure, (c) planning and
      planning products, (d) implementation actions, (e) activities and collaborations,
      (f) anticipated intermediate outcomes, and (g) expected asthma related health
      outcomes. Measurements are quantitative and qualitative, and data generated by
      these methods are used as ends in themselves and as a way to confirm or inform
      other measures. Evaluation has been an integral part of the planning and
      implementation phases of the Allies coalition work, with a priority of involving
      all of the partners in conceiving of and deciding upon the elements of
      assessment.

PMID- 16636156
TI  - Engaging the community in coalition efforts to address childhood asthma.
AB  - For health improvement efforts to effectively address community needs, community
      members must be engaged in planning and implementing public health initiatives.
      For Allies Against Asthma's coalitions, the community included not only the
      subpopulation of individuals who suffer disproportionately from asthma but also
      the individuals and institutions that surround them. Through a quantitative self
      assessment survey, informal discussion among coalition leadership, and interviews
      with key informants, data relevant to community engagement identified a number of
      important ways the Allies coalitions approached community involvement.
      Respondents' comments made clear that the way the coalitions conduct their work
      is often as important as what they do. Across coalitions, factors that were
      identified as important for community involvement included (a) establishing a
      commitment to community involvement, (b) building trust, (c) making participation
      feasible and comfortable, (d) responding to community identified needs, (e)
      providing leadership development opportunities, and (f) building a shared
      commitment to desired outcomes.

PMID- 16636157
TI  - Engaging health care providers in coalition activities.
AB  - Health care providers play a key role in promoting and participating in asthma
      coalition activities. Barriers to participation include lack of time, concern
      about coalition effectiveness, and unfamiliarity with community-based approaches
      to health issues. Despite this, the Allies Against Asthma coalitions were
      successful at involving health care providers in leadership roles, on advisory
      committees, and as research and clinical experts. Successful engagement
      strategies included presentation of data illustrating need for improved asthma
      care, identification of clinicians who were involved in caring for children with
      uncontrolled asthma, and education regarding the added value of a coalition and
      benefits of participation. Despite barriers to participation, health care
      providers felt that their participation in asthma coalitions helped them to
      develop collaborative relationships with other agencies, increase their
      professional knowledge and skills with regard to asthma management, and improve
      access to priority populations.

PMID- 16636158
TI  - Childhood asthma surveillance by community coalitions.
AB  - Multiple benefits can accrue when community coalitions conduct asthma
      surveillance activities. Surveillance data are used to identify children with
      asthma, assess disease burden and needs in the community, understand the illness
      and risk factors, identify children with asthma who are undertreated, plan
      community interventions, evaluate the effect of interventions, and monitor
      trends. These data, which are used to inform coalition and program decisions and
      to evaluate asthma interventions, can also be used to strengthen state and
      national asthma surveillance efforts and to inform clinical practice and public
      health policies. Local coalition data collection represents a complementary
      approach to national asthma surveillance, allowing action at the local level and
      showing how local findings vary from national observations. The Allies Against
      Asthma coalitions developed several practical means to conduct childhood asthma
      surveillance that informed coalition efforts and facilitated innovative linkages
      among government officials, health care providers, community agencies, families,
      and academicians and/or researchers.

PMID- 16636159
TI  - Improving quality of care and promoting health care system change: The role of
      community-based coalitions.
AB  - As part of their community action plans, the Allies Against Asthma coalitions
      have developed efforts to improve quality of care and promote health care system
      change. All the coalitions have used an interdisciplinary collaborative approach
      to design these strategies and demonstrated a range of intervention approaches
      appropriate to their local context and circumstances. The coalitions' collective
      experience suggests that coalitions provide three key forces for quality
      improvement and change that may be lacking in the current fragmented U.S. health
      care system--motivation to change the status quo, integration across systems, and
      accountability for results. The collaborative and empowering processes that a
      coalition model encourages and the direct advocacy opportunity provided to the
      consumer appear to bring these forces into play.

PMID- 16636160
TI  - Allies community health workers: Bridging the gap.
AB  - Allies Against Asthma coalitions each employ a community health worker (CHW)
      program as part of its community action plan. The structure and management of CHW
      programs vary in response to the resources and needs of the local community, as
      do the roles and characteristics of the CHWs hired. All programs utilize CHWs to
      provide community-based education and/or outreach to community members, primarily
      in their homes. Using an asthma action plan, most Allies CHW programs function as
      an extension of and link to the clinician, providing basic asthma education and
      care coordination in a supportive, family-friendly setting, context, and
      location. Community health workers rely heavily on relationship building and
      family empowerment to assist families in improving asthma control. Working within
      a coalition framework helps integrate the CHW program into other services and
      resources in the community. As participants in coalition activities, CHWs often
      bring an important and meaningful viewpoint to the coalition.

PMID- 16636161
TI  - Coalition-based approaches for addressing environmental issues in childhood
      asthma.
AB  - Outdoor air pollution and the indoor environment have been shown to cause or
      exacerbate childhood asthma. Allies Against Asthma coalitions implemented a broad
      range of activities to reduce or remediate indoor exposure to asthma
      environmental triggers for children with asthma including education and trigger
      remediation, physician and other health care provider education, and policy
      efforts to improve air quality in homes and schools. Outdoor environmental
      triggers were addressed through programs to increase education and awareness and
      efforts to change policies related to environmental conditions. Implementation of
      such efforts was complicated by the lack of safe and affordable housing and the
      amount of time and resources necessary to address policy change. Keys to success
      included promoting coordination and partnerships among coalition members,
      implementation of consistent messages, and building a broad and unified voice for
      policy change.

PMID- 16636162
TI  - The coalition process at work: Building care coordination models to control
      chronic disease.
AB  - Asthma is a highly prevalent and frequently misunderstood chronic disease with
      significant morbidity. Integrating client services at the patient-centered level
      and using coalitions to build coordinated, linked systems to affect care may
      improve outcomes. All seven Allies Against Asthma coalitions identified
      inefficient, inconsistent, and/or fragmented care as issues for their
      communities. In response, the coalitions employed a collaborative process to
      identify and address problems related to system fragmentation and to improve
      coordination of care. Each coalition developed a variety of interventions related
      to its specific needs and assets, stakeholders, stage of coalition formation, and
      the dynamic structure of its community. Despite common barriers in forming
      alliances with busy providers and their staff, organizing administrative
      structures among interinstitutional cultures, enhancing patient and/or family
      involvement, interacting with multiple insurers, and contending with health
      system inertia, the coalitions demonstrated the ability to produce coordinated
      improvements to existing systems of care.

PMID- 16636163
TI  - Integrating asthma prevention and control: the roles of the coalition.
AB  - Activities addressing pediatric asthma are often fragmented. Allies coalitions
      promoted integration, the alignment of concurrent asthma control activities
      across and within sectors. Systems integration describes activities from an
      organizational perspective. Activities included developing a shared vision,
      promoting consistency in asthma education and self-management support, improving
      adherence to clinical guidelines, advocating jointly for policy change, and
      seeking funds collaboratively. Service integration describes activities focused
      on ensuring seamless, comprehensive services through coordination within and
      across organizations. Activities included use of community health workers (CHWs)
      and nurses for care coordination, program cross-referral, and clinical quality
      improvement. Integration is a sustainable role for coalitions as it requires
      fewer resources than service delivery and results in institutionalization of
      system changes. Organizations that seek integration of asthma control may
      benefit.

PMID- 16636164
TI  - Allies against asthma: a midstream comment on sustainability.
AB  - The ability of a coalition to sustain its impact in a community over time is a
      vital element of success. Four sustainability strategies have emerged among
      Allies Against Asthma coalitions: (a) resource development; (b)
      institutionalization; (c) system change, including policy change; and (d)
      capacity building. Although it is too early to determine their ultimate success,
      a number of important lessons have been learned about the coalitions'
      sustainability efforts: (a) sustainability must be considered as a planning
      principle, (b) data demonstrating success will enhance efforts to sustain worthy
      efforts, (c) ongoing communication and relationship building are critical
      elements of sustainability, (d) considering sustainability can help guide
      membership recruitment efforts, (e) coalitions with previous asthma and/or
      coalition experience may be better prepared to address sustainability within a
      short project period, and (f) although difficult to fund, the coalition
      infrastructure itself is key to successfully sustaining outcomes and activities.

PMID- 16636166
TI  - Features of the metabolic syndrome and diabetes mellitus as predictors of aortic
      valve calcification in the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Calcific aortic valve disease is common in the elderly, is correlated
      with common cardiovascular risk factors, and is associated with increased
      cardiovascular event risk; however, whether metabolic syndrome is associated with
      an increased prevalence of aortic valve calcium (AVC) is not known. METHODS AND
      RESULTS: The prevalence of AVC, as assessed by computed tomography, was compared
      in 6780 Multi-Ethnic Study of Atherosclerosis (MESA) participants with metabolic
      syndrome (n=1550; National Cholesterol Education Program's Adult Treatment Panel
      III [ATP III] criteria), diabetes mellitus (n=1016), or neither condition
      (n=4024). The prevalence of AVC for those with neither condition, metabolic
      syndrome, or diabetes mellitus was, respectively, 8%, 12%, and 17% in women
      (P<0.001) and 14%, 22%, and 24% in men (P<0.001). Compared with those with
      neither condition, the adjusted relative risks for the presence of AVC were 1.45
      (95% CI 1.11 to 1.90) for metabolic syndrome and 2.12 (95% CI 1.54 to 2.92) for
      diabetes mellitus in women and 1.70 (95% CI 1.32 to 2.19) for metabolic syndrome
      and 1.73 (95% CI 1.33 to 2.25) for diabetes mellitus in men. There was a graded,
      linear relationship between AVC prevalence and the number of metabolic syndrome
      components in both women and men (both P<0.001). Similar results were obtained
      when the International Diabetes Federation metabolic syndrome definition was
      used. CONCLUSIONS: In the MESA cohort, the metabolic syndrome and diabetes
      mellitus are associated with increased risk of AVC, and AVC prevalence is
      increased with increasing number of metabolic syndrome components.

PMID- 16636167
TI  - Heart failure during cardiac pacing.
AB  - BACKGROUND: Right ventricular apical (RVA) pacing creates abnormal left
      ventricular contraction, hypertrophy, and reduced pump function. The adverse
      effects of ventricular desynchronization may explain the association of RVA
      pacing with an increased risk of heart failure hospitalization (HFH) in clinical
      trials. METHODS AND RESULTS: Baseline and postimplantation variables were used to
      predict HFH in the Mode Selection Trial, a 2010-patient, 6-year trial of dual
      chamber (DDDR) versus ventricular (VVIR) pacing in sinus node dysfunction. A Cox
      model showed that New York Heart Association (NYHA) class at baseline and follow
      up predicted HFH (hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.74
      5.79 for NYHA class III/IV and HR, 2.17; 95% CI, 1.54-3.04 for NYHA class II
      versus class I); other predictors were heart failure (HR, 2.30; 95% CI, 1.70
      3.11), atrioventricular (AV) block (HR, 1.48; 95% CI, 1.11-1.97), and myocardial
      infarction (MI)(HR, 1.37; 95% CI, 1.00-1.86). Postimplantation predictors were
      VVIR cumulative percent ventricular pacing (Cum%VP) >80 (HR, 3.58; 95% CI, 1.72
      7.45), DDDR Cum%VP >40 or VVIR Cum%VP < or =80 (HR, 1.81; 95% CI, 0.94-3.50)
      versus DDDR Cum%VP < or =40; whether QRS duration (QRSd) was paced or spontaneous
      (HR, 2.21; 95% CI, 1.39-3.54; spontaneous versus paced); and drugs for atrial
      fibrillation (HR, 1.60; 95% CI, 1.19-2.15). Low baseline ejection fraction (EF)
      and postimplantation RVA-paced or spontaneous QRSd predicted HFH; the increased
      risk with QRSd was steeper for normal versus low EF (HR, 1.18; 95% CI, 1.11-1.27;
      versus HR, 1.08; 95% CI, 1.01-1.15; for a 10-ms increase); at a QRSd of
      approximately 200 ms, normal- and low-EF patients had equivalent risk. HFH risk
      nearly doubled when VVIR Cum%VP was < or =80 or DDDR Cum%VP was >40 versus DDDR
      Cum%VP < or =40 and was additive with other risk factors. CONCLUSIONS:
      Differences in HFH risk can be explained by interactions between substrate
      (atrial fibrillation, AV conduction, heart failure, MI, EF) and pacing promoters
      (ventricular desynchronization-paced QRSd and Cum%VP, and AV desynchronization
      pacing mode). Management of RVA pacing is important for reducing the risk of HFH,
      particularly among patients with low EF and heart failure.

PMID- 16636168
TI  - Invasive assessment of the coronary microcirculation: superior reproducibility
      and less hemodynamic dependence of index of microcirculatory resistance compared
      with coronary flow reserve.
AB  - BACKGROUND: A simple, reproducible invasive method for assessing the coronary
      microcirculation is lacking. A novel index of microcirculatory resistance (IMR)
      has been shown in animals to correlate with true microvascular resistance and,
      unlike coronary flow reserve (CFR), to be independent of the epicardial artery.
      We sought to compare the reproducibility and hemodynamic dependence of IMR with
      CFR in humans. METHODS AND RESULTS: Using a pressure-temperature sensor-tipped
      coronary wire, thermodilution-derived CFR and IMR were measured, along with
      fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the
      following hemodynamic conditions: (1) twice at baseline; (2) during right
      ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside;
      and (4) during intravenous dobutamine infusion. Mean CFR did not change during
      baseline measurements or during nitroprusside infusion but decreased during
      pacing (from 3.1+/-1.1 at baseline to 2.3+/-1.2 during pacing, P<0.05) and during
      dobutamine infusion (from 3.0+/-1.0 to 1.7+/-0.6 with dobutamine, P<0.0001). By
      comparison, mean values for IMR and FFR remained similar throughout all
      hemodynamic conditions. The mean coefficient of variation between 2 baseline
      measurements was significantly lower for IMR (6.9+/-6.5%) and FFR (1.6+/-1.6%)
      than for CFR (18.6+/-9.6%; P<0.01). Mean correlation between baseline
      measurements and each hemodynamic intervention was superior for IMR (r=0.90+/
      0.05) and FFR (r=0.86+/-0.12) compared with CFR (r=0.70+/-0.05; P<0.05).
      CONCLUSIONS: Compared with CFR, IMR provides a more reproducible assessment of
      the microcirculation, which is independent of hemodynamic perturbations.
      Simultaneous measurement of FFR and IMR may provide a comprehensive and specific
      assessment of coronary physiology at both epicardial and microvascular levels,
      respectively.

PMID- 16636169
TI  - Coffee consumption and coronary heart disease in men and women: a prospective
      cohort study.
AB  - BACKGROUND: We examined the association between long-term habitual coffee
      consumption and risk of coronary heart disease (CHD). METHODS AND RESULTS: We
      performed a prospective cohort study with 44,005 men and 84,488 women without
      history of cardiovascular disease or cancer. Coffee consumption was first
      assessed in 1986 for men and in 1980 for women and then repeatedly every 2 to 4
      years; the follow-up continued through 2000. We documented 2173 incident cases of
      coronary heart disease (1449 nonfatal myocardial infarctions and 724 fatal cases
      of CHD) among men and 2254 cases (1561 nonfatal myocardial infarctions and 693
      fatal cases of CHD) among women. Among men, after adjustment for age, smoking,
      and other CHD risk factors, the relative risks (RRs) of CHD across categories of
      cumulative coffee consumption (<1 cup/mo, 1 cup/mo to 4 cups/wk, 5 to 7 cups/wk,
      2 to 3 cups/d, 4 to 5 cups/d, and > or =6 cups/d) were 1.0, 1.04 (95% confidence
      interval 0.91 to 1.17), 1.02 (0.91 to 1.15), 0.97 (0.86 to 1.11), 1.07 (0.88 to
      1.31), and 0.72 (0.49 to 1.07; P for trend=0.41); among women, the RRs were 1.0,
      0.97 (0.83 to 1.14), 1.02 (0.90 to 1.17), 0.84 (0.74 to 0.97), 0.99 (0.83 to
      1.17), and 0.87 (0.68 to 1.11; P for trend=0.08). Stratification by smoking
      status, alcohol consumption, history of type 2 diabetes mellitus, and body mass
      index gave similar results. Similarly, we found no effect when the most recent
      coffee consumption was examined. RRs for quintiles of caffeine intake varied from
      0.97 (0.84 to 1.10) in the second quintile to 0.97 (0.84 to 1.11) in the highest
      quintile (P for trend=0.82) in men and from 1.02 (0.90 to 1.16) to 0.97 (0.85 to
      1.11; P for trend=0.37) in women. CONCLUSIONS: These data do not provide any
      evidence that coffee consumption increases the risk of CHD.

PMID- 16636170
TI  - Understanding the coronary heart disease versus total cardiovascular mortality
      paradox: a method to enhance the comparability of cardiovascular death statistics
      in the United States.
AB  - BACKGROUND: Coronary heart disease (CHD) represents the largest share of
      cardiovascular disease in the United States, but there are conspicuous
      discrepancies between CHD and total cardiovascular death rates across the states,
      possibly due in part to variations in physician assignment of causes of death.
      Our aim was to identify exogenous individual- and community-level predictors of
      cause-of-death assignment and variability and to use these predictors to improve
      the comparability of CHD mortality estimates across states. METHODS AND RESULTS:
      We performed a multinomial logistic regression analysis to estimate the effect of
      individual- and community-level factors on the likelihood of a death being
      certified as 1 of 3 ill-defined clusters (general atherosclerosis and unspecified
      heart disease, heart failure, and cardiac arrest) relative to being certified as
      CHD. The individual-level variables were the decedent's race, sex, age,
      education, and place of death; the community-level variable was the number of
      cardiologists per capita. We used the model to estimate state-level CHD rates
      that are standardized with regard to the levels of individual- and community
      level determinants of cause-of-death assignment. Decedents who died in hospitals
      and in counties with more cardiologists per capita were more likely to be
      assigned to CHD than to the ill-defined categories, as were white males relative
      to other race-sex combinations. Adjustment for these factors resulted in
      substantially improved correlation between death rates for CHD and all
      cardiovascular causes. Increases in CHD death rates across states after
      adjustment for external predictors of cause-of-death assignment ranged from 2%
      (North Dakota) to 72% (Washington, DC); New York had a decrease (1%) in CHD death
      rates after adjustment. Nationally, CHD death rates increased 10% for males and
      15% for females. The total number of deaths in 2001 attributed to CHD in patients
      over 30 years of age rose from 433,625 to 489,836 after adjustment. CONCLUSIONS:
      Greater presence of medical knowledge at the time of death, reflected by place of
      death and cardiologists per capita, reduces the use of the ill-defined
      cardiovascular clusters. Racial and gender effects on CHD assignment may reflect
      disparities in access to care and quality of care. By adjusting for differentials
      in these parameters, a comparable and consistent set of CHD mortality estimates
      can be created. The role of the exogenous predictors in validity and
      comparability of cause-of-death statistics should be confirmed in carefully
      designed validation autopsy studies.

PMID- 16636171
TI  - CD73/ecto-5'-nucleotidase protects against vascular inflammation and neointima
      formation.
AB  - BACKGROUND: Although CD73/ecto-5'-nucleotidase has been implicated in maintaining
      vasoprotection, its role in regulating endothelial adhesion molecule or
      inflammatory monocyte recruitment (eg, in the context of vascular injury) remains
      to be defined. METHODS AND RESULTS: Compared with wild-type mice, CD73-deficient
      (CD73(-/-)) mice exhibit increased luminal staining and protein and transcript
      expression for vascular cell adhesion molecule (VCAM)-1 in carotid arteries. In
      vitro, aortic endothelial cells (ECs) from CD73(-/-) mice display an upregulation
      of mRNA and protein expression of VCAM-1, associated with increased nuclear
      factor (NF)-kappaB activity, as determined by chromatin cross-linking and
      immunoprecipitation or quantitative p65 binding assays. CD73(-/-) ECs and carotid
      arteries perfused ex vivo supported increased monocyte arrest under flow
      conditions, which was mediated by alpha(4beta1) integrin. After wire injury of
      carotid arteries, CD73 expression and activity were upregulated in wild-type
      mice, whereas neointimal plaque formation and macrophage content were increased
      in CD73(-/-) mice versus wild-type mice, concomitant with elevated NF-kappaB
      activation, luminal VCAM-1 expression, and soluble VCAM-1 concentrations. In
      contrast, reconstitution of wild-type mice with CD73(-/-) versus CD73(+/+) BM did
      not significantly exacerbate neointima formation. Treatment with the specific A2A
      receptor agonist ATL-146e reversed the increased VCAM-1 transcript and protein
      expression in CD73(-/-) ECs and inhibited monocyte arrest on CD73(-/-) ECs.
      Continuous infusion of ATL-146e prevented neointima formation in CD73(-/-) mice.
      CONCLUSIONS: Our data epitomize the importance of vascular CD73 in limiting
      endothelial activation and monocyte recruitment via generation of adenosine
      acting through the A2A receptor, providing a molecular basis for therapeutic
      protection against vascular inflammation and neointimal hyperplasia.

PMID- 16636172
TI  - Akt1 is required for physiological cardiac growth.
AB  - BACKGROUND: Postnatal growth of the heart chiefly involves nonproliferative
      cardiomyocyte enlargement. Cardiac hypertrophy exists in a "physiological" form
      that is an adaptive response to long-term exercise training and as a
      "pathological" form that often is a maladaptive response to provocative stimuli
      such as hypertension and aortic valvular stenosis. A signaling cascade that
      includes the protein kinase Akt regulates the growth and survival of many cell
      types, but the precise role of Akt1 in either form of cardiac hypertrophy is
      unknown. METHODS AND RESULTS: To evaluate the role of Akt1 in physiological
      cardiac growth, akt1(-/-) adult murine cardiac myocytes (AMCMs) were treated with
      IGF-1, and akt1(-/-) mice were subjected to exercise training. akt1(-/-) AMCMs
      were resistant to insulin-like growth factor-1-stimulated protein synthesis. The
      akt1(-/-) mice were found to be resistant to swimming training-induced cardiac
      hypertrophy. To evaluate the role of Akt in pathological cardiac growth, akt1(-/
      ) AMCMs were treated with endothelin-1, and akt1(-/-) mice were subjected to
      pressure overload by transverse aortic constriction. Surprisingly, akt1(-/-)
      AMCMs were sensitized to endothelin-1-induced protein synthesis, and akt1(-/-)
      mice developed an exacerbated form of cardiac hypertrophy in response to
      transverse aortic constriction. CONCLUSIONS: These results establish Akt1 as a
      pivotal regulatory switch that promotes physiological cardiac hypertrophy while
      antagonizing pathological hypertrophy.

PMID- 16636173
TI  - Role of T lymphocytes and interferon-gamma in ischemic stroke.
AB  - BACKGROUND: Although lymphocyte recruitment and activation are associated with
      cerebral ischemia-reperfusion (I/R) injury, the contributions of specific
      lymphocyte subpopulations and lymphocyte-derived interferon-gamma (IFN-gamma) to
      stroke remain unknown. The objectives of this study were to define the
      contribution of specific populations of lymphocytes to the inflammatory and
      prothrombogenic responses elicited in the cerebral microvasculature by I/R and to
      investigate the role of T-cell-associated IFN-gamma in the pathogenesis of
      ischemic stroke. METHODS AND RESULTS: Middle cerebral artery occlusion was
      induced for 1 hour (followed by 4 or 24 hours of reperfusion) in wild-type mice
      and mice deficient in lymphocytes (Rag1(-/-)), CD4+ T cells, CD8+ T cells, B
      cells, or IFN-gamma. Platelet and leukocyte adhesion was assessed in cortical
      venules with intravital video microscopy. Neurological deficit and infarct volume
      were determined 24 hours after reperfusion. Rag1(-/-), CD4+ T-cell(-/-), CD8+ T
      cell(-/-), and IFN-gamma(-/-) mice exhibited comparable significant reductions in
      I/R-induced leukocyte and platelet adhesion compared with wild-type mice exposed
      to I/R. Infarct volume was reduced and I/R-induced neurological deficit was
      improved in immunodeficient Rag1(-/-) mice. These protective responses were
      reversed in Rag1(-/-) mice reconstituted with either wild-type or, to a lesser
      extent, IFN-gamma(-/-) splenocytes. B-cell-deficient mice failed to show
      improvement against ischemic stroke injury. CONCLUSIONS: These findings indicate
      that CD4+ and CD8+ T lymphocytes, but not B lymphocytes, contribute to the
      inflammatory and thrombogenic responses, brain injury, and neurological deficit
      associated with experimental stroke. Although IFN-gamma plays a pivotal role in
      stroke-induced inflammatory responses, T lymphocytes appear to be a minor source
      of this cytokine.

PMID- 16636174
TI  - Physiological and clinical consequences of relief of right ventricular outflow
      tract obstruction late after repair of congenital heart defects.
AB  - BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common
      problem after repair of congenital heart disease. Percutaneous pulmonary valve
      implantation (PPVI) can treat this condition without consequent pulmonary
      regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical
      and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18
      patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a
      total of 93 who had this procedure for various indications. All had a right
      ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without
      important pulmonary regurgitation (less than mild or regurgitant fraction <10% on
      magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue
      Doppler echocardiography, and MRI were performed before and within 50 days of
      PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right
      ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization.
      Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic
      (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial
      systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7
      to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The
      tricuspid annular velocity was not maintained on intermediate follow-up. Right
      ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas
      effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0%
      to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4
      mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection
      fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO,
      which leads to an early improvement in biventricular performance. Furthermore, it
      reduces symptoms and improves exercise tolerance. These findings have important
      implications for the management of this increasingly common condition.

PMID- 16636175
TI  - Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on
      plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein
      particle size: the Framingham Heart Study.
AB  - BACKGROUND: Apolipoprotein A5 gene (APOA5) variation is associated with plasma
      triglycerides (TGs). However, little is known about whether dietary fat modulates
      this association. METHODS AND RESULTS: We investigated the interaction between
      APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant
      like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and
      1147 women who were Framingham Heart Study participants. Polymorphisms -1131T>C
      and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene
      diet interactions between the -1131T>C polymorphism and polyunsaturated fatty
      acid (PUFA) intake were found (P<0.001) in determining fasting TGs, RLP
      concentrations, and particle size, but these interactions were not found for the
      56C>G polymorphism. The -1131C allele was associated with higher fasting TGs and
      RLP concentrations (P<0.01) in only the subjects consuming a high-PUFA diet (>6%
      of total energy). No heterogeneity by sex was found. These interactions showed a
      dose-response effect when PUFA intake was considered as a continuous variable
      (P<0.01). Similar interactions were found for the sizes of VLDL and LDL
      particles. Only in carriers of the -1131C allele did the size of these particles
      increase (VLDL) or decrease (LDL) as PUFA intake increased (P<0.01). We further
      analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA-APOA5
      interactions were specific for dietary n-6 fatty acids. CONCLUSIONS: Higher n-6
      (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL
      size and decreased LDL size in APOA5 -1131C carriers, suggesting that n-6 PUFA
      rich diets are related to a more atherogenic lipid profile in these subjects.

PMID- 16636176
TI  - Matrix metalloproteinases/tissue inhibitors of metalloproteinases: relationship
      between changes in proteolytic determinants of matrix composition and structural,
      functional, and clinical manifestations of hypertensive heart disease.
AB  - BACKGROUND: Chronic hypertension may cause left ventricular (LV) remodeling,
      alterations in cardiac function, and the development of chronic heart failure
      (CHF). Changes in the composition of the extracellular matrix (ECM) known to
      occur in hypertension are believed to be causally related to these structural,
      functional, and clinical outcomes. However, whether the determinants of ECM
      composition, such as the balance between ECM proteases (matrix metalloproteinases
      [MMPs]) and their tissue inhibitors [TIMPs]), are altered in hypertensive heart
      disease is unknown. METHODS AND RESULTS: Plasma MMP-2, -9, and -13 values, TIMP-1
      and -2 values, and Doppler echocardiography images were obtained for 103 subjects
      divided into 4 groups: (1) reference subjects (CTL) with no evidence of
      cardiovascular disease, (2) hypertensive (HTN) subjects with controlled blood
      pressure and no LV hypertrophy, (3) hypertensive subjects with controlled blood
      pressure and with LV hypertrophy (HTN+LVH) but no CHF, and (4) hypertensive
      subjects with controlled blood pressure, LVH, and CHF (HTN+LVH+CHF). Compared
      with CTL, patients with HTN had no significant changes in any MMP or TIMP.
      Patients with HTN+LVH had decreased MMP-2 and MMP-13 values and increased MMP-9
      values. Only patients with HTN+LVH+CHF had increased TIMP-1 values. A TIMP-1
      level >1200 ng/mL was predictive of CHF. CONCLUSIONS: Patients with hypertension
      but normal LV structure and function had normal MMP/TIMP profiles. Changes in MMP
      profiles that favor decreased ECM degradation were associated with LVH and
      diastolic dysfunction. An increased TIMP-1 level predicted the presence of CHF.
      Although these findings should be confirmed in a larger prospective study, these
      data do suggest that changes in the MMP/TIMP balance may play an important role
      in the structural, functional, and clinical manifestations of hypertensive heart
      disease.

PMID- 16636177
TI  - Cardiology patient page. Syncope.

PMID- 16636178
TI  - Images in cardiovascular medicine. Natural tissue engineering inside a
      ventricular septum defect occluder.

PMID- 16636179
TI  - Images in cardiovascular medicine. Transition from left ventricular hypertrophy
      to massive fibrosis in the cardiac variant of Fabry disease.

PMID- 16636180
TI  - Images in cardiovascular medicine. External carotid artery-internal jugular vein
      fistula: a complication of internal jugular cannulation.

PMID- 16636181
TI  - Letter regarding article by Ejiri et al, "possible role of brain-derived
      neurotrophic factor in the pathogenesis of coronary artery disease".

PMID- 16636182
TI  - Letter regarding article by Coronel et al, "right ventricular fibrosis and
      conduction delay in a patient with clinical signs of Brugada syndrome: a combined
      electrophysiological, genetic, histopathologic, and computational study".

PMID- 16636183
TI  - A positive future for stem cell research?

PMID- 16636184
TI  - New molecular mechanism in diastolic heart failure.

PMID- 16636185
TI  - The end of granulocyte colony-stimulating factor in acute myocardial infarction?
      Reaping the benefits beyond cytokine mobilization.

PMID- 16636186
TI  - Novel transgenic rabbit model sheds light on the puzzling role of matrix
      metalloproteinase-12 in atherosclerosis.

PMID- 16636187
TI  - New insights into the initiation of atrial fibrillation: a detailed
      intraindividual and interindividual analysis of the spontaneous onset of atrial
      fibrillation using new diagnostic pacemaker features.
AB  - BACKGROUND: This study investigated onset scenarios of atrial fibrillation (AF),
      the first phase of the Atrial Fibrillation Therapy (AFT) trial, to determine
      potential arrhythmogenic triggers as targets for atrial pacing algorithms that
      have been proposed for prevention of AF. METHODS AND RESULTS: Ninety-eight
      patients (58 men; age 65+/-11 years) with recurrent, symptomatic, drug-refractory
      AF and a conventional pacemaker indication in 31 of 98 received a dual-chamber
      pacemaker. Using novel diagnostic pacemaker features AF onset scenarios were
      prospectively evaluated in 612 AF episodes during a 2-month monitoring period,
      with atrial pacing limited to 40 bpm. The most common onset scenario was
      premature atrial complexes (PACs) before AF (48% onsets per patient), followed by
      bradycardia (33%), sudden onset (17%), and tachycardia (0%). Combinations of
      onset scenarios were frequent (median 2 different scenarios per patient). A main
      study finding was the significance of repetitive AF, with 33% of onsets per
      patient being initiated within 5 minutes of a previous AF episode. Sudden onsets
      were more frequent among patients with than without repetitive AF (24% versus 0%
      onsets per patient, P=0.011), whereas the proportion of PACs before AF was not
      statistically different (50% versus 37%, P=0.52); however, patients with
      repetitive AF had more PACs per hour (72 versus 29, P=0.023) and a higher number
      of AF episodes per day (17 versus 0, P=0.001) and were more likely to have at
      least 1 PAC-related onset (90% versus 53%, P<0.0001). CONCLUSIONS: Novel
      diagnostic pacemaker features allowed a detailed individual analysis of rate and
      rhythm changes before AF and thus uncovered a substantial intraindividual and
      interindividual variability of AF onset scenarios.

PMID- 16636188
TI  - Macrophage metalloelastase accelerates the progression of atherosclerosis in
      transgenic rabbits.
AB  - BACKGROUND: Macrophage metalloelastase (matrix metalloproteinase [MMP]-12) is
      upregulated in atherosclerotic lesions and aneurysm; thus, increased MMP-12
      activity may play an important role in the pathogenesis of atherosclerosis.
      However, the pathological roles of MMP-12 in the initiation and progression of
      atherosclerosis have not been defined. METHODS AND RESULTS: We compared the
      susceptibility of MMP-12 transgenic (Tg) rabbits to cholesterol-rich diet-induced
      atherosclerosis with that of non-Tg littermate rabbits. The rabbits were
      maintained at either relatively lower levels of hypercholesterolemia for shorter
      periods or higher levels of hypercholesterolemia for longer periods through a
      diet containing different amounts of cholesterol. We found no significant
      difference in the aortic atherosclerotic lesion size or quality between Tg and
      non-Tg rabbits at lower hypercholesterolemia. At higher hypercholesterolemia for
      longer periods, however, Tg rabbits developed more extensive atherosclerosis in
      the aortas and coronary arteries than did non-Tg rabbits. Histological
      examinations revealed that atherosclerotic lesions of Tg rabbits contained
      prominent macrophage infiltration associated with marked disruption of the
      elastic lamina in the tunica media with occasional formation of aneurysm-like
      lesions. Furthermore, increased expression of MMP-12 derived from macrophages was
      associated with elevated expression of MMP-3, suggesting that MMP-12 may play a
      pivotal role in the cascade activation of other MMPs, thereby exacerbating
      extracellular matrix degradation during the progression of atherosclerosis.
      CONCLUSIONS: Overexpression of MMP-12 causes accelerated atherosclerosis in Tg
      rabbits. These results suggest that macrophage-derived MMP-12 participates in the
      progression of atherosclerosis.

PMID- 16636189
TI  - Chronic thromboembolic pulmonary hypertension.

PMID- 16636190
TI  - Realizing the potential of carotid artery stenting: proposed paradigms for
      patient selection and procedural technique.
AB  - Carotid artery stenting, compared with carotid endarterectomy, is emerging as an
      effective and less invasive method of revascularization for extracranial carotid
      artery stenosis. Carotid stenting is established as the treatment of choice for
      certain high-risk patient subsets, and ongoing clinical trials are evaluating
      this method across a broader clinical spectrum, including asymptomatic patients.
      For carotid stenting to reach its full potential, an acceptable risk of
      periprocedural complications, particularly in low-risk patients, must be ensured
      (the "3% rule"). The present article provides an in-depth review of carotid
      stenting, with special emphasis on the process of risk stratification pertaining
      to clinical, anatomic, and procedural considerations necessary to optimize
      procedural safety and patient outcomes.

PMID- 16636191
TI  - Angiotensinogen modulates renal vasculature growth.
AB  - We have shown previously that angiotensinogen, like other members of the serine
      protease inhibitor family, has antiangiogenic properties in vitro on cultured
      endothelial cells and in ovo in the chick chorioallantoic membrane assay. The aim
      of this study was to show the effects of angiotensinogen on vascular wall
      remodeling in vivo. We measured the vessel wall thickness (tunica media) stained
      with an antibody to alpha-actin. In the kidney, arterioles were 21.5% thinner in
      male transgenic mice overexpressing human angiotensinogen than in male control
      animals. In other vascular beds, the arterial wall thickness was not affected. By
      using in situ hybridization and Northern blot analysis, human angiotensinogen
      expression was detected at a high level in the male kidney and at a much lower
      level in other organs. There is a relationship between the effect of
      angiotensinogen on arterial wall thickness and the local expression level of
      angiotensinogen in this model of transgenic mice. Because human angiotensinogen
      is not cleaved to a significant extent by mouse renin, the reduction in kidney
      arterial wall thickness is because of angiotensinogen itself and not angiotensin
      II, and we show that the reduction was not because of hypoplasia or hypotropia.
      In contrast, a marked difference in the expression of platelet-derived growth
      factor receptor-beta was observed in the kidney arterioles at day 5 when compared
      with controls. Altogether, these observations provide the first quantitative
      evidence that a high level of angiotensinogen expression can inhibit the growth
      of kidney artery walls in vivo.

PMID- 16636192
TI  - Amelioration of genetic hypertension by suppression of renal G protein-coupled
      receptor kinase type 4 expression.
AB  - Abnormalities in D1 dopamine receptor function in the kidney are present in some
      types of human essential and rodent genetic hypertension. We hypothesize that
      increased activity of G protein-coupled receptor kinase type 4 (GRK4) causes the
      impaired renal D1 receptor function in hypertension. We measured renal GRK4 and
      D1 and serine-phosphorylated D1 receptors and determined the effect of decreasing
      renal GRK4 protein by the chronic renal cortical interstitial infusion (4 weeks)
      of GRK4 antisense oligodeoxynucleotides (As-Odns) in conscious- uninephrectomized
      spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar
      Kyoto (WKY) rats. Basal GRK4 expression and serine-phosphorylated D1 receptors
      were &90% higher in SHRs than in WKY rats and were decreased to a greater extent
      in SHRs than in WKY rats with GRK4 As-Odns treatment. Basal renal D1 receptor
      protein was similar in both rat strains. GRK4 As-Odns, but not scrambled
      oligodeoxynucleotides, increased sodium excretion and urine volume, attenuated
      the increase in arterial blood pressure with age, and decreased protein excretion
      in SHRs, effects that were not observed in WKY rats. These studies provide direct
      evidence of a crucial role of renal GRK4 in the D1 receptor control of sodium
      excretion and blood pressure in genetic hypertension.

PMID- 16636193
TI  - Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and
      is reversed by aldosterone blocker.
AB  - Recent clinical studies implicate proteinuria as a key prognostic factor for
      renal and cardiovascular complications in hypertensives. The pathogenesis of
      proteinuria in hypertension is, however, poorly elucidated. Podocytes constitute
      the final filtration barrier in the glomerulus, and their dysfunction may play a
      pivotal role in proteinuria. In the present study, we examined the involvement of
      podocyte injury in Dahl salt-hypertensive rats, an animal model prone to
      hypertensive glomerulosclerosis, and explored the effects of inhibition of
      aldosterone. Four-week-old Dahl salt-resistant and salt-sensitive rats were fed a
      0.3% or 8.0% NaCl diet. Some salt-loaded Dahl salt-sensitive rats were treated
      with a selective aldosterone blocker eplerenone (1.25 mg/g diet) or hydralazine
      (0.5 mmol/L). After 6 weeks, salt-loaded Dahl salt-sensitive rats developed
      severe hypertension, proteinuria, and glomerulosclerosis. Immunostaining for
      nephrin, a constituent of slit diaphragm, was attenuated, whereas expressions of
      damaged podocyte markers desmin and B7-1 were upregulated in the glomeruli of
      salt-loaded Dahl salt-sensitive rats. Electron microscopic analysis revealed
      podocyte foot process effacement. Podocytes were already impaired at as early as
      2 weeks of salt loading in Dahl salt-sensitive rats, when proteinuria was
      modestly increased. Both eplerenone and hydralazine partially reduced systemic
      blood pressure as measured by indirect and direct methods in salt-loaded Dahl
      salt-sensitive rats, but only eplerenone dramatically improved podocyte damage
      and retarded the progression of proteinuria and glomerulosclerosis. Our findings
      suggest that podocyte injury underlies the glomerulopathy of Dahl salt
      hypertensive rats and that inhibition of aldosterone by eplerenone is protective
      against podocyte damage, proteinuria, and glomerulosclerosis in this hypertensive
      model.

PMID- 16636194
TI  - Long-term administration of rho-kinase inhibitor ameliorates renal damage in
      malignant hypertensive rats.
AB  - We have shown recently that fasudil, a Rho-kinase inhibitor, has renoprotective
      effects in salt-sensitive hypertensive rats. We hypothesized that activation of
      Rho-kinase is involved in the pathogenesis of glomerulosclerosis in malignant
      hypertensive rats. To test this hypothesis, we studied the following 4 groups:
      control Wistar-Kyoto rats, untreated deoxycorticosterone-acetate salt
      spontaneously hypertensive rats (DOCA-SHR), low-dose fasudil-treated DOCA-SHR,
      and high-dose fasudil-treated DOCA-SHR. After 3 weeks of treatment, the effects
      of fasudil were examined. DOCA-SHR was characterized by increased blood pressure
      (BP); increased kidney weight; decreased renal function; increased proteinuria;
      abnormal histological findings; increased monocyte/macrophage infiltration;
      increased urinary 8-isoprostran levels; increased gene expression of collagen I,
      collagen III, transforming growth factor-beta, and reduced nicotinamide-adenine
      dinucleotide phosphate oxidase subunits (p40phox, p47phox, and p67phox); and
      decreased gene expression of endothelial NO synthase (eNOS) in the renal cortex
      as compared with Wistar-Kyoto rats. Long-term high-dose fasudil treatment
      significantly improved renal function and histological findings without changing
      BP, as compared with untreated DOCA-SHR. Interestingly, long-term fasudil
      treatment significantly decreased monocyte/macrophage infiltration and urinary 8
      isoprostran excretion, in association with decreased mRNA levels of transforming
      growth factor-beta, collagen I, collagen III, and NADPH oxidase subunits
      (p40phox, p47phox, and p67phox), and increased mRNA levels of eNOS in the renal
      cortex. Long-term low-dose fasudil treatment tended to improve these variables
      slightly but did not affect most of them significantly. Our results suggest that
      long-term fasudil treatment provides renoprotective effects independent of BP
      lowering activity. These renoprotective effects are associated with inhibition of
      extracellular matrix gene expression, monocyte/macrophage infiltration, oxidative
      stress, and upregulation of eNOS gene expression.

PMID- 16636195
TI  - Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP
      activated protein kinase activation in vascular endothelial cells.
AB  - AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP
      ratio and plays a central role in regulation of energy homeostasis and metabolic
      stress. Metformin has been shown to activate AMPK. We hypothesized that metformin
      may prevent nuclear factor kappaB (NF-kappaB) activation in endothelial cells
      exposed to inflammatory cytokines. Metformin was observed to activate AMPK, as
      well as its downstream target, phosphoacetyl coenzyme A carboxylase, in human
      umbilical vein endothelial cells (HUVECs). Metformin also dose-dependently
      inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF
      alpha-induced IkappaB kinase activity. Furthermore, metformin attenuated the TNF
      alpha-induced gene expression of various proinflammatory and cell adhesion
      molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular
      adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs. A
      pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside
      (AICAR), dose-dependently inhibited TNF-alpha- and interleukin-1beta-induced NF
      kappaB reporter gene expression. AICAR also suppressed the TNF-alpha- and
      interleukin-1beta-induced gene expression of vascular cell adhesion molecule-1, E
      selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein
      1 in HUVECs. The small interfering RNA for AMPKalpha1 attenuated metformin or
      AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a
      possible role of AMPK in the regulation of cell inflammation. In light of these
      findings, we suggest that metformin attenuates the cytokine-induced expression of
      proinflammatory and adhesion molecule genes by inhibiting NF-kappaB activation
      via AMPK activation. Thus, it might be useful to target AMPK signaling in future
      efforts to prevent atherogenic and inflammatory vascular disease.

PMID- 16636196
TI  - Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and
      ovariectomized deoxycorticosterone-acetate salt rats.
AB  - Water-free Na+ storage may buffer extracellular volume and mean arterial pressure
      (MAP) in spite of Na+ retention. We studied the relationship among internal Na+,
      K+, water balance, and MAP in Sprague-Dawley rats, with or without
      deoxycorticosterone-acetate (DOCA) salt, with or without ovariectomy (OVX). The
      rats were fed a low-salt (0.1% NaCl) or high-salt (8% NaCl) diet for 5 weeks.
      DOCA salt increased MAP (161+/-14 versus 123+/-4 mm Hg; P<0.05), and DOCA-OVX
      salt increased MAP further (181+/-22 mm Hg; P<0.05). DOCA salt increased the
      total body Na+ by &40% to 45%; however, water-free Na+ retention by osmotically
      inactive Na+ storage and by osmotically neutral Na+/K+ exchange allowed the rats
      to maintain the extracellular volume close to normal. DOCA-OVX salt rats showed
      similar Na+ retention. However, their osmotically inactive Na+ storage capacity
      was greatly reduced and only partially compensated by neutral Na+/K+ exchange,
      resulting in greater volume retention despite similar Na+ retention. For every 1%
      wet weight total body water gain, MAP increased by 2.3+/-0.2 mm Hg in DOCA salt
      rats and 2.5+/-0.3 mm Hg in DOCA-OVX salt rats. Because water-free Na+ retention
      buffered total body water content by 8% to 11% wet weight, we conclude that this
      internal Na+ escape buffered MAP. Extrarenal Na+ and volume balance seem to play
      an important role in long-term volume and MAP control.

PMID- 16636197
TI  - Hyperhomocysteinemia associated with decreased renal transsulfuration activity in
      Dahl S rats.
AB  - Elevated plasma homocysteine (Hcys) has been reported to participate in the
      development of arterial and glomerular sclerosis in Dahl salt-sensitive
      hypertensive (SS) rats. The mechanism resulting in hyperhomocysteinemia in these
      animals remains unknown. Disposal of Hcys in the kidneys plays an important role
      in regulating the plasma Hcys level. We, therefore, examined the activities and
      expressions of the enzymes involved in the metabolism of Hcys in the kidneys of
      SS rats, compared with that of Brown Norway rats and SSBN13 rats, a consomic
      subcolony of SS rats that carries a substituted chromosome 13 from Brown Norway
      rats. High-performance liquid chromatography analysis demonstrated that plasma
      Hcys levels were significantly higher in SS rats. The conversion of S
      adenosylhomocysteine into Hcys via S-adenosylhomocysteine hydrolase by renal
      tissue was not different among these 3 rat strains. However, the metabolic rate
      of Hcys into cysteine was markedly reduced in the SS rat kidneys. The mRNA and
      protein levels of cystathionine beta-synthase (CBS), one of the key enzymes in
      the transsulfuration pathway in the kidneys, were significantly lower in SS rats.
      In microdissected nephron segments, CBS mRNA was shown to be mainly present in
      renal proximal tubules (PTs). The mRNA levels of CBS in the PTs were also
      significantly decreased in SS rats, accompanied by a reduced CBS activity in PTs.
      We conclude that hyperhomocysteinemia is associated with a decreased activity and
      expression of CBS in renal PTs because of the defect of chromosome 13 in SS rats.

PMID- 16636198
TI  - Association study with 33 single-nucleotide polymorphisms in 11 candidate genes
      for hypertension in Chinese.
AB  - Essential hypertension is considered to be a typical complex disease with
      multifactorial etiology, which leads to inconsistent findings in genetic studies.
      One possibility of failure to replicate some single-locus results is that the
      underlying genetics of hypertension are not only based on multiple genes with
      minor effects but also on gene-gene interactions. To test this hypothesis, a case
      control study was constructed in Chinese subjects, detecting both single locus
      and multilocus effects. Eleven candidate genes were selected from biochemical
      pathways that have been implicated in the development and progression of
      hypertension, and 33 polymorphisms were evaluated in 503 hypertension patients
      and 490 age- and gender-matched controls. Single-locus associations, using
      traditional logistic regression analyses, and multilocus associations, using
      classification and regression trees and multivariate adaptive regression splines,
      were both explored in this study. Final models were selected using either
      Bonferroni correction or cross-validation. Three polymorphisms, TH*rs2070762,
      ADRB2*Q27E, and GRK4*A486V, were found to be independently associated with
      essential hypertension in Chinese subjects. In addition to these individual
      predictors, a potential interaction of CYP11B2-AGTR1 is also involved in the
      etiology of hypertension. These findings support the multigenic nature of the
      etiology of essential hypertension and propose a potential gene-gene interactive
      model for future studies.

PMID- 16636199
TI  - Cardiovascular function in mice during normal pregnancy and in the absence of
      endothelial NO synthase.
AB  - In humans, the increased cardiovascular demands of pregnancy are met by increases
      in cardiac output (CO), stroke volume (SV), plasma volume (PV), and cardiac and
      aortic inner dimensions and a concurrent decrease in arterial pressure that
      indicates a fall in total peripheral vascular resistance. The mechanisms
      responsible for these changes are incompletely understood, but NO synthase (NOS)
      is believed to play a central role. We assessed whether C57Bl/6J (B6) mice show
      similar changes and whether these changes are altered in mice lacking the gene
      for endothelial NOS (eNOS). The CO of B6 mice increased 28% by day 9.5 of
      gestation because of a 25% increase in SV, and increased 48% by day 17.5 because
      of a 41% increase in SV. The increase in SV at day 17.5 was associated with a 27%
      increase in PV, a 15% decrease in arterial pressure, and 10% to 15% increases in
      aortic and left-ventricular inner dimensions. In the absence of eNOS, CO
      increased 22% by day 9.5 because of increases in SV (14%) and heart rate (9%),
      but increased no further by day 17.5. SV near term was lower than B6 mice despite
      similar 26% increases in PV and 14% decreases in arterial pressure in association
      with blunted left-ventricular chamber enlargement. All reported changes are
      P<0.05. We conclude that cardiovascular changes during pregnancy are similar in
      B6 mice and humans. eNOS plays a critical role in increasing stroke volume in
      late gestation by promoting cardiac remodeling.

PMID- 16636200
TI  - Do allelic variants in alpha2A and alpha2C adrenergic receptors predispose to
      hypertension in blacks?
AB  - Sequence variations in the human alpha2 adrenergic receptor genes (ADRA2A and
      ADRA2C) have been implicated as a cause of hypertension in blacks. Although
      certain alleles are selectively enriched in blacks, their association with
      hypertension is based on small convenience samples and has not been evaluated in
      larger populations. From a stratified random population sample of 3398
      individuals (52% blacks), we obtained DNA samples together with an in-home health
      interview, 10 in-home measurements of blood pressure, and cardiac MRI. We tested
      for associations among hypertension, untreated blood pressure, and parameters of
      hypertensive heart disease with 2 alleles, a DraI restriction fragment length
      polymorphism in the ADRA2A gene and a deletion of residues 322 to 325 in the
      ADRA2C gene. Although both alleles were selectively enriched in this black
      population, we found no association of either allele with hypertension, untreated
      blood pressure, or any of the cardiac function parameters. In a logistic model
      that controlled for age, body mass index, diabetes, and smoking, the adjusted
      odds ratio (OR) for hypertension was 1.0 (95% CI, 0.8 to 1.2), and 1.0 (95% CI,
      0.9 to 1.2) for ADRA2A and ADRA2C variant alleles. In subjects not receiving
      prescription blood pressure medication, neither of these alleles, alone or in
      combination, was predictive of blood pressure, heart rate, left ventricular mass,
      cardiac output, systemic vascular resistance, or aortic compliance. Both the DraI
      restriction fragment length polymorphism in ADRA2A and the ADRA2C (Del 322 to
      325) can be excluded as major candidate alleles for hypertension in blacks.

PMID- 16636201
TI  - Feedback network controls photoreceptor output at the layer of first visual
      synapses in Drosophila.
AB  - At the layer of first visual synapses, information from photoreceptors is
      processed and transmitted towards the brain. In fly compound eye, output from
      photoreceptors (R1-R6) that share the same visual field is pooled and transmitted
      via histaminergic synapses to two classes of interneuron, large monopolar cells
      (LMCs) and amacrine cells (ACs). The interneurons also feed back to photoreceptor
      terminals via numerous ligand-gated synapses, yet the significance of these
      connections has remained a mystery. We investigated the role of feedback synapses
      by comparing intracellular responses of photoreceptors and LMCs in wild-type
      Drosophila and in synaptic mutants, to light and current pulses and to
      naturalistic light stimuli. The recordings were further subjected to rigorous
      statistical and information-theoretical analysis. We show that the feedback
      synapses form a negative feedback loop that controls the speed and amplitude of
      photoreceptor responses and hence the quality of the transmitted signals. These
      results highlight the benefits of feedback synapses for neural information
      processing, and suggest that similar coding strategies could be used in other
      nervous systems.

PMID- 16636202
TI  - Functional characterization of homo- and heteromeric channel kinases TRPM6 and
      TRPM7.
AB  - TRPM6 and TRPM7 are two known channel kinases that play important roles in
      various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6
      cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However,
      whether TRPM6 encodes functional channels is controversial. Here we demonstrate
      several signature features of TRPM6 that distinguish TRPM6 from TRPM7 and TRPM6/7
      channels. We show that heterologous expression of TRPM6 but not the mutant
      TRPM6(S141L) produces functional channels with divalent cation permeability
      profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7
      complexes. TRPM6 exhibits unique unitary conductance that is 2- and 1.5-fold
      bigger than that of TRPM7 and TRPM6/7. Moreover, micromolar levels of 2
      aminoethoxydiphenyl borate (2-APB) maximally increase TRPM6 but significantly
      inhibit TRPM7 channel activities; whereas millimolar concentrations of 2-APB
      potentiate TRPM6/7 and TRPM7 channel activities. Furthermore, Mg2+ and Ca2+ entry
      through TRPM6 is enhanced three- to fourfold by 2-APB. Collectively, these
      results indicate that TRPM6 forms functional homomeric channels as well as
      heteromeric TRPM6/7 complexes. The unique characteristics of these three channel
      types, TRPM6, TRPM7, and TRPM6/7, suggest that they may play different roles in
      vivo.

PMID- 16636203
TI  - Voltage clamp fluorometric measurements on a type II Na+-coupled Pi
      cotransporter: shedding light on substrate binding order.
AB  - Voltage clamp fluorometry (VCF) combines conventional two-electrode voltage clamp
      with fluorescence measurements to detect protein conformational changes, as
      sensed by a fluorophore covalently attached to the protein. We have applied VCF
      to a type IIb Na+-coupled phosphate cotransporter (NaPi-IIb), in which a novel
      cysteine was introduced in the putative third extracellular loop and expressed in
      Xenopus oocytes. Labeling this cysteine (S448C) with methanethiosulfonate (MTS)
      reagents blocked cotransport function, however previous electrophysiological
      studies (Lambert G., I.C. Forster, G. Stange, J. Biber, and H. Murer. 1999. J.
      Gen. Physiol. 114:637-651) suggest that substrate interactions with the protein
      can still occur, thus permitting study of a limited subset of states. After
      labeling S448C with the fluorophore tetramethylrhodamine MTS, we detected voltage
      and substrate-dependent changes in fluorescence (DeltaF), which suggested that
      this site lies in an environment that is affected by conformational change in the
      protein. DeltaF was substrate dependent (no DeltaF was detectable in 0 mM Na+)
      and showed little correlation with presteady-state charge movements, indicating
      that the two signals provide insight into different underlying physical
      processes. Interpretation of ion substitution experiments indicated that the
      substrate binding order differs from our previous model (Forster, I., N.
      Hernando, J. Biber, and H. Murer. 1998. J. Gen. Physiol. 112:1-18). In the new
      model, two (rather than one) Na+ ions precede Pi binding, and only the second Na+
      binding transition is voltage dependent. Moreover, we show that Li+, which does
      not drive cotransport, interacts with the first Na+ binding transition. The
      results were incorporated in a new model of the transport cycle of type II Na+/Pi
      cotransporters, the validity of which is supported by simulations that
      successfully predict the voltage and substrate dependency of the experimentally
      determined fluorescence changes.

PMID- 16636204
TI  - Relationship between pore occupancy and gating in BK potassium channels.
AB  - Permeant ions can have significant effects on ion channel conformational changes.
      To further understand the relationship between ion occupancy and gating
      conformational changes, we have studied macroscopic and single-channel gating of
      BK potassium channels with different permeant monovalent cations. While the
      slopes of the conductance-voltage curve were reduced with respect to potassium
      for all permeant ions, BK channels required stronger depolarization to open only
      when thallium was the permeant ion. Thallium also slowed the activation and
      deactivation kinetics. Both the change in kinetics and the shift in the GV curve
      were dependent on the thallium passing through the permeation pathway, as well as
      on the concentration of thallium. There was a decrease in the mean open time and
      an increase in the number of short flicker closing events with thallium as the
      permeating ion. Mean closed durations were unaffected. Application of previously
      established allosteric gating models indicated that thallium specifically alters
      the opening and closing transition of the channel and does not alter the calcium
      activation or voltage activation pathways. Addition of a closed flicker state
      into the allosteric model can account for the effect of thallium on gating.
      Consideration of the thallium concentration dependence of the gating effects
      suggests that the flicker state may correspond to the collapsed selectivity
      filter seen in crystal structures of the KcsA potassium channel under the
      condition of low permeant ion concentration.

PMID- 16636205
TI  - The light peak of the electroretinogram is dependent on voltage-gated calcium
      channels and antagonized by bestrophin (best-1).
AB  - Mutations in VMD2, encoding bestrophin (best-1), cause Best vitelliform macular
      dystrophy (BMD), adult-onset vitelliform macular dystrophy (AVMD), and autosomal
      dominant vitreoretinochoroidopathy (ADVIRC). BMD is distinguished from AVMD by a
      diminished electrooculogram light peak (LP) in the absence of changes in the
      flash electroretinogram. Although the LP is thought to be generated by best-1, we
      find enhanced LP luminance responsiveness with normal amplitude in Vmd2-/- mice
      and no differences in cellular Cl- currents in comparison to Vmd2+/+ littermates.
      The putative Ca2+ sensitivity of best-1, and our recent observation that best-1
      alters the kinetics of voltage-dependent Ca2+ channels (VDCC), led us to examine
      the role of VDCCs in the LP. Nimodipine diminished the LP, leading us to survey
      VDCC beta-subunit mutant mice. Lethargic mice, which harbor a loss of function
      mutation in the beta4 subunit of VDCCs, exhibited a significant shift in LP
      luminance response, establishing a role for Ca2+ in LP generation. When
      stimulated with ATP, which increases [Ca++]I, retinal pigment epithelial cells
      derived from Vmd2-/- mice exhibited a fivefold greater response than Vmd2+/+
      littermates, indicating that best-1 can suppress the rise in [Ca2+]I associated
      with the LP. We conclude that VDCCs regulated by a beta4 subunit are required to
      generate the LP and that best-1 antagonizes the LP luminance response potentially
      via its ability to modulate VDCC function. Furthermore, we suggest that the loss
      of vision associated with BMD is not caused by the same pathologic process as the
      diminished LP, but rather is caused by as yet unidentified effects of best-1 on
      other cellular processes.

PMID- 16636206
TI  - Soluble mediators, not cilia, determine airway surface liquid volume in normal
      and cystic fibrosis superficial airway epithelia.
AB  - A key aspect of the lung's innate defense system is the ability of the
      superficial epithelium to regulate airway surface liquid (ASL) volume to maintain
      a 7-mum periciliary liquid layer (PCL), which is required for cilia to beat and
      produce mucus flow. The mechanisms whereby airway epithelia regulate ASL height
      to >or=7 microm are poorly understood. Using bumetanide as an inhibitor of Cl-
      secretion, and nystatin as an activator of Na+ absorption, we found that a
      coordinated "blending" of both Cl- secretion and Na+ absorption must occur to
      effect ASL volume homeostasis. We then investigated how ASL volume status is
      regulated by the underlying epithelia. Cilia were not critical to this process as
      (a) ASL volume was normal in cultures from patients with primary ciliary
      dyskinesia with immotile cilia, and (b) in normal cultures that had not yet
      undergone ciliogenesis. However, we found that maneuvers that mimic deposition of
      excess ASL onto the proximal airways, which occurs during mucociliary clearance
      and after glandular secretion, acutely stimulated Na+ absorption, suggesting that
      volume regulation was sensitive to changes in concentrations of soluble mediators
      in the ASL rather than alterations in ciliary beating. To investigate this
      hypothesis further, we added potential "soluble mediators" to the ASL. ASL volume
      regulation was sensitive to a channel-activating protein (CAP; trypsin) and a CAP
      inhibitor (aprotinin), which regulated Na+ absorption via changes in epithelial
      Na+ channel (ENaC) activity in both normal and cystic fibrosis cultures. ATP was
      also found to acutely regulate ASL volume by inducing secretion in normal and
      cystic fibrosis (CF) cultures, while its metabolite adenosine (ADO) evoked
      secretion in normal cultures but stimulated absorption in CF cultures.
      Interestingly, the amount of ASL/Cl- secretion elicited by ATP/ADO was influenced
      by the level of CAP-induced Na+ absorption, suggesting that there are important
      interactions between the soluble regulators which finely tune ASL volume.

PMID- 16636207
TI  - Prevention of relapse after quitting smoking: a systematic review of trials.
AB  - BACKGROUND: After initially successful quit attempts, many people return to
      smoking within a year, reducing the public health benefits of investment in
      smoking cessation. We aimed to assess whether interventions designed to prevent
      relapse after a successful quit attempt reduce the proportion of recent quitters
      who return to smoking. METHODS: We searched the Cochrane Tobacco Addiction Review
      Group trials' register. We selected randomized or quasi-randomized controlled
      trials of relapse prevention interventions with a minimum follow-up of 6 months.
      We included people who quit on their own, underwent enforced abstinence, or were
      in treatment programs. We included trials comparing relapse prevention
      interventions with no intervention or cessation plus relapse prevention with
      cessation intervention alone. Two of us independently extracted data from each
      report, with disagreements referred to a third author. RESULTS: Forty-two studies
      met the inclusion criteria. The most common interventions were skills training to
      identify and resolve tempting situations and extended treatment contact. A few
      studies tested pharmacotherapy. We separately analyzed studies that randomized
      abstainers and those that randomized participants before their quit date. Within
      subgroups of trials, pooled odds ratios ranged from 0.86 to 1.30, and in most
      analyses, 95% confidence intervals included 1. Most studies had limited power to
      detect moderate differences between interventions. CONCLUSION: The evidence to
      date does not support the adoption of skills training or other specific
      interventions to help individuals who have successfully quit smoking to avoid
      relapse, but this is an important area for future study.

PMID- 16636208
TI  - Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials.
AB  - To evaluate the efficacy and tolerability of oxycodone in cancer-related pain, we
      conducted a systematic review of randomized controlled trials. Four studies,
      comparing oral oxycodone with either oral morphine (n = 3) or oral hydromorphone
      (n = 1), were suitable for meta-analysis. Standardized mean differences in pain
      scores comparing oxycodone with control groups were pooled using random-effects
      models. Overall, there was no evidence that mean pain scores differed between
      oxycodone and control drugs (pooled standardized mean difference, 0.04; 95%
      confidence interval [CI], -0.29 to 0.36; P = .8; I(2) = 62%). In meta-regression
      analyses, pain scores were higher for oxycodone compared with morphine (0.20; 95%
      CI, -0.04 to 0.44) and lower compared with hydromorphone (-0.36; 95% CI, -0.71 to
      0.00), although these effect sizes were small. The efficacy and tolerability of
      oxycodone are similar to morphine, supporting its use as an opioid for cancer
      related pain.

PMID- 16636209
TI  - Association of impaired diurnal blood pressure variation with a subsequent
      decline in glomerular filtration rate.
AB  - BACKGROUND: Most healthy people exhibit a decrease in systolic blood pressure
      (SBP) at night. A drop of less than 10% from mean daytime values (nondipping) is
      associated with chronic kidney disease, insulin resistance, and cardiovascular
      events. Whether nondipping precedes a decline in renal function remains unclear.
      We hypothesized that nondipping would predict a decline in the glomerular
      filtration rate (GFR) over time. METHODS: Consecutive patients referred for
      ambulatory blood pressure monitoring were included in our retrospective cohort if
      they had a serum creatinine level noted at the time of their ambulatory blood
      pressure recording and a follow-up creatinine level recorded at least 1 year
      later. Mean day and night SBPs were compared (nighttime SBP-daytime [corrected]
      SBP ratio). We defined nondipping as a nighttime [corrected] SBP-daytime
      [corrected] SBP ratio higher than 0.90. The GFR was calculated using the
      Modification of Diet in Renal Disease 4-variable equation. RESULTS: Of 322
      patients included, 137 were dippers and 185 were nondippers; their mean baseline
      GFRs were 80.5 mL/min per 1.73 m(2) and 76.4 mL/min per 1.73 m(2), respectively.
      During a median follow-up of 3.2 years, the GFRs remained stable among dippers
      (mean change, 1.3%) but declined among nondippers (mean change, -15.9%) (P<.001).
      The creatinine levels increased by more than 50% in 2 dippers (1.5%) and in 32
      nondippers (17.3%) (P<.001). These findings persisted after adjustment for other
      predictors of GFR decline. CONCLUSION: Blunted diurnal blood pressure variation
      is associated with a subsequent deterioration in renal function that is
      independent of SBP load and other risk factors for renal impairment.

PMID- 16636210
TI  - Comparison of bleeding in patients with nonvalvular atrial fibrillation treated
      with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time
      course and sites of bleeding, and risk factors for bleeding.
AB  - BACKGROUND: Ximelagatran is a novel direct thrombin inhibitor that can be
      administered as a fixed oral dose, without the need for anticoagulant monitoring.
      METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial
      fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial
      Fibrillation III and V trials to compare bleeding outcomes in patients who
      received ximelagatran, 36 mg twice daily, or warfarin sodium (target
      international normalized ratio, 2.0-3.0). We determined annual risk of bleeding
      (any, major), case-fatality rate, time course and anatomic sites of major
      bleeding, and risk factors for major bleeding with ximelagatran and warfarin
      treatment. RESULTS: Annual incidence of any bleeding was 31.75% with ximelagatran
      and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval
      [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with
      ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2
      42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran-
      and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of
      major bleeding was higher with warfarin than ximelagatran after 24 months of
      treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable
      with both treatments. Risk factors for bleeding with ximelagatran were as follows
      (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P
      = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P =
      .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68;
      1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were
      previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69
      3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02).
      CONCLUSIONS: Treatment with ximelagatran, 36 mg twice daily, is associated with a
      lower risk of bleeding than warfarin in patients with nonvalvular atrial
      fibrillation. Aspirin use and increasing age were associated with an increased
      risk of bleeding in ximelagatran- and warfarin-treated patients.

PMID- 16636211
TI  - Effect of weight loss and exercise on frailty in obese older adults.
AB  - BACKGROUND: Obesity exacerbates the age-related decline in physical function and
      causes frailty in older persons. However, appropriate treatment for obese older
      persons is unknown. We evaluated the effects of weight loss and exercise therapy
      on physical function and body composition in obese older persons. METHODS: We
      screened 40 obese older volunteers and eventually randomized 27 frail obese older
      volunteers to treatment or control groups. Treatment consisted of 6 months of
      weekly behavioral therapy for weight loss in conjunction with exercise training 3
      times per week. Physical function was evaluated with measurements of frailty
      (Physical Performance Test, peak oxygen consumption, and Functional Status
      Questionnaire); strength, gait, and balance tests; body composition with dual
      energy x-ray absorptiometry; and quality of life using the Medical Outcomes
      Survey 36-Item Short-Form Health Survey. Results are reported as mean +/- SD.
      RESULTS: Two subjects in the treatment group did not comply with the
      intervention, and 1 subject in the control group withdrew. Analyses included all
      27 subjects originally randomized to the treatment and control groups. The
      treatment group lost 8.4% +/- 5.6% of body weight, whereas weight did not change
      in the control group (+0.5% +/- 2.8%; P<.001). Compared with the control group,
      fat mass decreased (-6.6 +/- 3.4 vs +1.7 +/- 4.1 kg; P<.001), without a change in
      fat-free mass (-1.2 +/- 2.1 vs -1.0 +/- 3.5 kg; P = .75) in the treatment group.
      The Physical Performance Test score (2.6 +/- 2.5 vs 0.1 +/- 1.0; P = .001), peak
      oxygen consumption (1.7 +/- 1.6 vs 0.3 +/- 1.1 mL/min per kilogram; P = .02), and
      Functional Status Questionnaire score (2.9 +/- 3.7 vs -0.2 +/- 3.9; P = .02)
      improved in treated subjects compared with control subjects. Treatment also
      improved strength, walking speed, obstacle course, 1-leg limb stance time, and
      health survey physical subscale scores (all P<.05). CONCLUSION: These findings
      suggest that weight loss and exercise can ameliorate frailty in obese older
      adults. Trial Registration clinicaltrials.gov Identifier: NCT00146133.

PMID- 16636212
TI  - Effects of calcium supplementation on clinical fracture and bone structure:
      results of a 5-year, double-blind, placebo-controlled trial in elderly women.
AB  - BACKGROUND: Increased dietary calcium intake has been proposed as a population
      based public health intervention to prevent osteoporotic fractures. We have
      examined whether calcium supplementation decreases clinical fracture risk in
      elderly women and its mechanism of action. METHODS: Five-year, double-blind,
      placebo-controlled study of 1460 women recruited from the population and older
      than 70 years (mean age, 75 years) who were randomized to receive calcium
      carbonate, 600 mg twice per day, or identical placebo. The primary end points
      included clinical incident osteoporotic fractures, vertebral deformity, and
      adverse events ascertained in 5 years. Bone structure was also measured using
      dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography
      of the heel, and peripheral quantitative computed tomography of the distal
      radius. RESULTS: Among our patients, 16.1% sustained 1 or more clinical
      osteoporotic fractures. In the intention-to-treat analysis, calcium
      supplementation did not significantly reduce fracture risk (hazard ratio, 0.87;
      95% confidence interval, 0.67-1.12). However, 830 patients (56.8%) who took 80%
      or more of their tablets (calcium or placebo) per year had reduced fracture
      incidence in the calcium compared with the placebo groups (10.2% vs 15.4%; hazard
      ratio, 0.66; 95% confidence interval, 0.45-0.97). Calcium-treated patients had
      improved quantitative ultrasonography findings of the heel, femoral neck and
      whole-body dual x-ray absorptiometry data, and bone strength compared with
      placebo-treated patients. Of the 92 000 adverse events recorded, constipation was
      the only event increased by the treatment (calcium group, 13.4%; placebo group,
      9.1%). CONCLUSION: Supplementation with calcium carbonate tablets supplying 1200
      mg/d is ineffective as a public health intervention in preventing clinical
      fractures in the ambulatory elderly population owing to poor long-term
      compliance, but it is effective in those patients who are compliant.

PMID- 16636213
TI  - Depressive symptoms after acute myocardial infarction: evidence for highest rates
      in younger women.
AB  - BACKGROUND: Depression is common in patients hospitalized with acute myocardial
      infarction (AMI). In the community, younger women are uniquely prone to
      depression. Whether younger women are also more likely to have depression during
      hospitalization with AMI is unknown. METHODS: A total of 2498 AMI patients (1284
      patients <or=60 years; 814 women and 1684 men) were enrolled from 19 US centers
      in the Prospective Registry Evaluating Outcomes After Myocardial Infarction:
      Events and Recovery (PREMIER) study between January 2003 and June 2004.
      Depression was assessed at the time of hospitalization and was defined as a
      Primary Care Evaluation of Mental Disorders Brief Patient Health Questionnaire
      (PHQ) score of 10 or higher. RESULTS: Younger (<or=60 years) patients had higher
      mean PHQ scores than older patients (6.4 vs 5.0; P<.001) and women had higher
      mean PHQ scores than men (6.8 vs 5.2; P<.001). When stratified by both age and
      sex, younger women had the highest PHQ scores (8.2; P<.001 for the sex-age
      interaction). The prevalence of depression was 40% in women 60 years or younger,
      21% in women older than 60, 22% in men 60 or younger, and 15% in men older than
      60. In a logistic model adjusted for study center, race, medical history, and
      coronary heart disease risk factors, the odds of depression for women 60 years or
      younger were significantly higher than for the other sex-age groups and were 3.1
      times higher than the reference group of men older than 60 years. CONCLUSIONS:
      The prevalence of depression is high in younger women with AMI. Because
      depression after AMI has been associated with adverse outcomes, younger women, a
      high-risk group compared with men, may particularly benefit from aggressive
      screening and treatment of post-AMI depression.

PMID- 16636214
TI  - Proteinuria and risk for stroke and coronary heart disease during 27 years of
      follow-up: the Honolulu Heart Program.
AB  - BACKGROUND: Urinary protein excretion has been linked to coronary heart disease
      (CHD); the relationship to stroke is less clear. We assessed whether urine
      dipstick screening for protein predicted stroke and CHD in the Honolulu Heart
      Program cohort. METHODS: Prospective, observational study of 6252 Japanese
      American men in Honolulu aged 45 to 68 years. Proteinuria was detected by means
      of urine dipstick screening during the first and third examinations. Subjects
      were classified as having no proteinuria if results were negative at both
      examinations, transient proteinuria if results were positive at 1 examination,
      and persistent proteinuria if results were positive at both examinations.
      Relative risk was derived using those subjects with no proteinuria as the
      reference. Outcomes were assessed through 27 years. RESULTS: No proteinuria was
      found in 92.8% of subjects, transient proteinuria in 6.1%, and persistent
      proteinuria in 1.1%. The age-adjusted incident stroke rates were 3.7, 7.3, and
      11.8 per 1000 person-years in subjects with no, transient, or persistent
      proteinuria, respectively (P<.001). Age-adjusted rates of incident CHD were 9.4,
      15.8, and 35.2 events per 1000 person-years, respectively (P<.001). Using Cox
      proportional hazards models, adjusting for age, body mass index, physical
      activity, smoking status, cholesterol level, presence of hypertension or diabetes
      mellitus, and alcohol consumption, the relative risk for 27-year incident stroke
      was 1.66 (95% confidence interval, 1.21-2.30; P = .002) with transient
      proteinuria and 2.84 (95% confidence interval, 1.51-5.34; P = .001) with
      persistent proteinuria, and relative risk for 27-year incident CHD was 1.48 (95%
      confidence interval, 1.19-1.83; P<.001) with transient proteinuria and 3.72 (95%
      confidence interval, 2.62-5.27; P<.001) with persistent proteinuria. CONCLUSION:
      Proteinuria detected at urine dipstick screening independently predicted
      increased risk for incident stroke and incident CHD over 27 years in this cohort.

PMID- 16636215
TI  - Prospective study of health status preferences and changes in preferences over
      time in older adults.
AB  - BACKGROUND: Instructional forms of advance care planning depend on the ability of
      patients to predict their future treatment preferences. However, preferences may
      change with changes in patients' health states. METHODS: We conducted in-home
      interviews of 226 older community-dwelling persons with advanced cancer,
      congestive heart failure, or chronic obstructive pulmonary disease at least every
      4 months for up to 2 years. Patients were asked to rate whether treatment for
      their illness would be acceptable if it resulted in 1 of 4 health states.
      RESULTS: The likelihood of rating as acceptable a treatment resulting in mild
      (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.16) or severe (OR,
      1.06; 95% CI, 1.03-1.09) functional disability increased with each month of
      participation. Patients who experienced a decline in their ability to perform
      instrumental activities of daily living were more likely to rate as acceptable
      treatment resulting in mild (OR, 1.23; 95% CI, 1.08-1.40) or severe (OR, 1.23;
      95% CI, 1.11-1.37) disability. Although the overall likelihood of rating
      treatment resulting in a state of pain as acceptable did not change over time
      (OR, 0.98; 95% CI, 0.96-1.01), patients who had moderate to severe pain were more
      likely to rate this treatment as acceptable (OR, 2.55; 95% CI, 1.56-4.19) than
      were those who did not have moderate to severe pain. CONCLUSIONS: For some
      patients, the acceptability of treatment resulting in certain diminished states
      of health increases with time, and increased acceptability is more likely among
      patients experiencing a decline in that same domain. These changes pose a
      challenge to advance care planning, which asks patients to predict their future
      treatment preferences.

PMID- 16636216
TI  - Racial differences in trust in health care providers.
AB  - BACKGROUND: Although trust in health care providers (physicians, nurses, and
      others) may be lower among African Americans compared with whites, limited
      information is available on factors that are associated with low trust in these
      populations. This study evaluated the association between trust in health care
      providers and prior health care experiences, structural characteristics of health
      care, and sociodemographic factors among African Americans and whites. METHODS:
      National survey of 954 non-Hispanic adult African Americans (n = 432) and whites
      (n = 522). RESULTS: African Americans (44.7%) were more likely than whites
      (33.5%) to report low levels of trust in health care providers (chi(2) = 12.40,
      P<.001). Fewer quality interactions with health care providers had a significant
      effect on low trust among African Americans (odds ratio [OR], 3.23; 95%
      confidence interval [CI], 1.97-5.29; P<.001) and whites (OR, 3.99; 95% CI, 2.44
      6.50; P<.001). Among African Americans, respondents whose usual source of care
      was not a physician's office were most likely to report low trust (OR, 1.73; 95%
      CI, 1.15-2.61; P = .02), whereas among whites, women (OR, 1.54; 95% CI, 1.04
      2.30; P = .03) and respondents with fewer annual health care visits (OR, 1.52;
      95% CI, 1.02-2.28; P = .04) were most likely to report low trust. CONCLUSIONS:
      Compared with whites, African Americans were most likely to report low trust in
      health care providers. While fewer quality interactions with health care
      providers were associated significantly with low trust in both populations, usual
      source of medical care was only associated with low trust among African
      Americans, whereas sex and the number of annual health care visits were
      associated with low trust among whites. Different factors may influence trust in
      health care providers among African Americans and whites.

PMID- 16636217
TI  - Effects of etanercept in patients with the metabolic syndrome.
AB  - BACKGROUND: Adipose-derived cytokines, including tumor necrosis factor alpha, may
      contribute to the inflammation that occurs in the metabolic syndrome. We
      investigated the effects of inhibition of tumor necrosis factor alpha with
      etanercept in patients with the metabolic syndrome. METHODS: Fifty-six subjects
      with the metabolic syndrome were randomized to administration of either
      etanercept or identical placebo, 50 mg subcutaneously once a week for 4 weeks.
      The C-reactive protein level was the primary end point. Effects on other
      inflammatory markers (including fibrinogen, interleukin 6, and adiponectin),
      insulin sensitivity, lipid levels, and body composition were also determined.
      RESULTS: Baseline characteristics were similar between the groups. Two subjects
      dropped out of each group, and etanercept was well tolerated throughout the
      study. The C-reactive protein levels decreased significantly in the treated
      compared with the placebo group (-2.4 +/- 0.4 vs 0.5 +/- 0.7 mg/L; P<.001).
      Adiponectin levels rose significantly in the etanercept group compared with the
      placebo group (0.8 +/- 0.4 vs -0.3 +/- 0.3 microg/mL; P = .03). Fibrinogen levels
      decreased (-68 +/- 16 vs -2 +/- 31 mg/dL [-2.0 +/- 0.47 vs -0.06 +/- 0.91
      micromol/L]; P = .04) and interleukin 6 levels tended to decrease (-1.2 +/- 0.8
      vs 0.5 +/- 0.5 ng/L; P = .07) in the etanercept-treated subjects compared with
      placebo, respectively. No changes occurred in body composition parameters or
      insulin sensitivity, but high-density lipoprotein levels tended to decrease in
      the etanercept group (-1 +/- 1 vs 2 +/- 1 mg/dL [-0.03 +/- 0.03 vs 0.05 +/- 0.03
      mmol/L]; P = .06) compared with the placebo group. CONCLUSIONS: Etanercept
      reduces C-reactive protein levels and tends to improve other inflammatory
      cardiovascular risk indexes in patients with the metabolic syndrome. Etanercept
      may interrupt the inflammatory cascade that occurs with abdominal obesity.
      Further, longer-term studies are needed to determine the effects of tumor
      necrosis factor alpha inhibition on cardiovascular disease in patients with the
      metabolic syndrome.

PMID- 16636218
TI  - Prognostic impact of prolonged ventricular repolarization in hypertension.
AB  - BACKGROUND: QT interval prolongation on the surface electrocardiogram (ECG)
      predicts cardiovascular complications in high-risk subjects, but its prognostic
      role in uncomplicated hypertension has been understudied. METHODS: For up to 13
      years (average, 5.3 years), we followed up 2110 white patients with initially
      untreated essential hypertension (mean +/- SD age, 49 +/- 12 years; 55% men)
      without prevalent cardiovascular or renal disease who underwent 12-lead ECG
      before therapy. We excluded patients with ECG abnormalities including ischemia,
      necrosis, complete bundle branch block, atrial fibrillation, arrhythmias, and
      ventricular preexcitation. RESULTS: Heart rate-corrected QT interval (QTc) showed
      a weak but significant direct association with systolic blood pressure (r = 0.07;
      P<.001), diastolic blood pressure (r = 0.11; P<.001), and Cornell voltage (r =
      0.06; P = .006). During follow-up, 84 patients developed new-onset ischemic heart
      disease (0.75 event per 100 patient-years). After adjustment (Cox model) for the
      effects of age, sex, diabetes mellitus, serum cholesterol level, serum creatinine
      level, smoking, left ventricular hypertrophy, and 24-hour systolic blood
      pressure, patients with a prolonged QTc (>or=450 milliseconds in women and
      >or=440 milliseconds in men) had a nearly 2-fold increase in risks of coronary
      events (hazard ratio, 1.95; 95% confidence interval, 1.12-3.42; P = .02) and
      cardiovascular death (hazard ratio, 2.05; 95% confidence interval, 1.03-4.37; P =
      .04). Coronary heart disease risk was independently higher by 33% (95% confidence
      interval, +7% to +66%; P = .01) for each 32-millisecond increase in QTc.
      CONCLUSIONS: Prolonged ventricular repolarization is a risk factor for ischemic
      heart disease and cardiovascular mortality in subjects with uncomplicated
      hypertension. Its prognostic significance adds to that of several traditional
      cardiovascular risk factors, including left ventricular hypertrophy.

PMID- 16636219
TI  - Predicting medical and surgical complications of carotid endarterectomy:
      comparing the risk indexes.
AB  - BACKGROUND: Several generic cardiac risk assessment tools predict perioperative
      cardiac complications, but their ability to predict a broader range of medical,
      neurologic, and surgical complications is unknown. METHODS: A multicenter
      retrospective observational cohort study of 1998 patients undergoing carotid
      endarterectomy (CEA). Complications within 30 days of surgery were assessed by
      medical record review, including death or nonfatal stroke and cardiac, noncardiac
      medical, minor neurologic, and wound complications. Logistic regression and
      receiver operating characteristic curve analyses assessed the predictive
      abilities of the Goldman, Detsky, Revised Cardiac Risk, and American Society of
      Anesthesiologists indexes and of 2 CEA-specific risk models (the Halm and Tu
      scores). RESULTS: Death or stroke occurred in 3.2% of patients, cardiac
      complications in 4.0%, noncardiac medical complications in 3.2%, minor neurologic
      complications in 6.9%, and wound complications in 6.0%. All risk models (except
      the Tu score) significantly predicted cardiac complications equally well (P<.05).
      All 6 risk models were equivalent in predicting noncardiac medical complications.
      Only the Revised Cardiac Risk Index and the 2 CEA-specific risk models (Halm and
      Tu scores) predicted death or stroke and minor neurologic and wound
      complications. The Halm score was superior in predicting death or stroke compared
      with the Tu score and the Revised Cardiac Risk Index (area under the receiver
      operating characteristic curve, 0.72 vs 0.62 and 0.61, respectively; P<.05).
      Patients with cardiac, noncardiac medical, minor neurologic, or wound
      complications had 3- to 16-fold increased odds of death or stroke. CONCLUSION:
      The Halm score CEA-specific risk model and the generic Revised Cardiac Risk Index
      predicted a broad range of medical, neurologic, and surgical complications
      following CEA.

PMID- 16636220
TI  - End-of-life decision making in Europe and Australia: a physician survey.
AB  - BACKGROUND: The frequencies with which physicians make different medical end-of
      life decisions (ELDs) may differ between countries, but comparison between
      countries has been difficult owing to the use of dissimilar research methods.
      METHODS: A written questionnaire was sent to a random sample of physicians from 9
      specialties in 6 European countries and Australia to investigate possible
      differences in the frequencies of physicians' willingness to perform ELDs and to
      identify predicting factors. Response rates ranged from 39% to 68% (N = 10 139).
      Using hypothetical cases, physicians were asked whether they would (probably)
      make each of 4 ELDs. RESULTS: In all the countries, 75% to 99% of physicians
      would withhold chemotherapy or intensify symptom treatment at the request of a
      patient with terminal cancer. In most cases, more than half of all physicians
      would also be willing to deeply sedate such a patient until death. However, there
      was generally less willingness to administer drugs with the explicit intention of
      hastening death at the request of the patient. The most important predictor of
      ELDs was a request from a patient with decisional capacity (odds ratio, 2.1
      140.0). Shorter patient life expectancy and uncontrollable pain were weaker
      predictors but were more stable across countries and across the various ELDs
      (odds ratios, 1.1-2.4 and 0.9-2.4, respectively). CONCLUSION: Cultural and legal
      factors seem to influence the frequencies of different ELDs and the strength of
      their determinants across countries, but they do not change the essence of
      decision making.

PMID- 16636221
TI  - Acupuncture may be ineffective for stroke.

PMID- 16636222
TI  - Epidemiology of depression in a Chinese rural population.

PMID- 16636223
TI  - Ocular neuromyotonia: video case report.

PMID- 16636224
TI  - Patient page. Slowing down a "slow" movement disorder: selegiline's benefit in
      treating Parkinson disease.

PMID- 16636225
TI  - MRI contrast extravasation with enlarging hyperacute thrombolysis-related
      hemorrhage.

PMID- 16636226
TI  - MR DWI does not substitute for stroke severity scores in predicting stroke
      outcome.

PMID- 16636227
TI  - Lowering cholesterol in patients with stroke: raising the standard.

PMID- 16636228
TI  - Using functional neuroimaging to study the brain's response to deep brain
      stimulation.

PMID- 16636229
TI  - Superficial siderosis.
AB  - BACKGROUND: Superficial siderosis (SS) of the CNS is caused by repeated slow
      hemorrhage into the subarachnoid space with resultant hemosiderin deposition in
      the subpial layers of the brain and spinal cord. Despite extensive
      investigations, the cause of bleeding is frequently undetermined. OBJECTIVES: To
      review the clinical and imaging features of 30 consecutive patients with SS and
      provide insights into the underlying causes of subarachnoid bleeding in this
      disabling disorder. METHODS: The authors reviewed the medical records of 30
      consecutive patients with clinical and MRI evidence of SS. RESULTS: The commonest
      neurologic manifestations included gait ataxia and hearing impairment. A clinical
      history of subarachnoid hemorrhage was relatively rare. Possible predisposing
      conditions were identified on history in 22 patients, the commonest being a prior
      trauma (15 patients). In addition to the characteristic MRI findings of SS, 18
      patients had abnormalities on MRI possibly related to chronic bleeding. The most
      common of these was the presence of a fluid-filled collection in the spinal canal
      seen in 14 patients. CONCLUSIONS: A history of prior subarachnoid hemorrhage is
      often absent in patients with superficial siderosis (SS). A past history of
      trauma is common. Prior intradural surgery may be an additional risk factor.
      Xanthochromia or the presence of red blood cells in the CSF is a common finding.
      Only rarely does angiography demonstrate the bleeding source. The presence of a
      fluid-filled collection in the spinal canal is a common finding on MRI and is
      likely related to the SS. With longitudinally extensive cavities, a dynamic CT
      myelogram may help localize the defect and direct the site of laminectomy.
      Surgical repair of a dural defect, if present, should be considered. Surgical
      correction of bleeding should be documented by CSF examination months after
      surgery. Friable vessels in the dural defect are a possible source of the chronic
      bleeding.

PMID- 16636230
TI  - Antiplatelets, ACE inhibitors, and statins combination reduces stroke severity
      and tissue at risk.
AB  - BACKGROUND: Antiplatelets (APL), angiotensin-converting enzyme (ACE) inhibitors
      (ACEI), and statins (STAT) are commonly used for stroke prevention. The authors
      examined whether combination therapy with these agents has additive protective
      effects in reducing ischemic stroke severity. METHODS: The authors
      retrospectively analyzed data from 210 consecutive patients presenting within 24
      hours of stroke onset. Baseline NIH Stroke Scale (NIHSS) score and diffusion
      weighted imaging (DWI), perfusion-weighted imaging (PWI), and PWI-DWI mismatch
      lesion volumes as clinical and radiologic measures of stroke severity were
      measured among patients who were not taking APL, ACEI, or STAT before stroke
      onset vs those who were taking APL alone or in combination with either ACEI,
      STAT, or both. RESULTS: Sixty-nine patients were not on APL, ACEI, or STAT at
      stroke onset; 47 were on APL alone, 43 on dual (14 APL + STAT, 29 APL + ACEI),
      and 20 on triple combination therapy. Patients on triple therapy had lower NIHSS
      score (p = 0.001) and smaller mean PWI-DWI mismatch lesion volumes (p = 0.03)
      than those on two agents, APL alone, or no prestroke therapy. Higher percentages
      of patients on triple therapy had shorter length of hospitalization and better
      functional status upon discharge. Age, risk factor profile, blood pressure,
      glucose levels, onset to evaluation time, stroke subtypes, and DWI lesion volumes
      were comparable among all groups. CONCLUSIONS: Prestroke use of available drugs
      for stroke prevention, in combination, may result in additive reduction in stroke
      severity, as measured by NIH Stroke Scale, and the volume of ischemic tissue at
      risk, as assessed by perfusion-weighted imaging-diffusion-weighted imaging
      mismatch. These findings require further validation in larger-scale, randomized,
      prospective studies.

PMID- 16636231
TI  - Statin treatment and adherence to national cholesterol guidelines after ischemic
      stroke.
AB  - BACKGROUND: National cholesterol guidelines have defined high vascular risk
      individuals as those who could potentially benefit most from statin therapy. The
      authors aimed to determine the rate of statin use, its predictors, and the
      achievement of national guideline target lipid goals among ischemic stroke
      survivors. METHODS: The authors abstracted data from the Vitamin Intervention for
      Stroke Prevention (VISP) study database from the United States and Canada to
      incorporate into algorithms for initiating statin therapy according to the
      National Cholesterol Education Program (NCEP) guidelines for high-risk
      individuals. The authors applied these algorithms to all study subjects.
      Univariate as well as multivariate associations for target lipid levels and
      statin implementation were then evaluated utilizing pertinent demographic,
      clinical, and laboratory data. RESULTS: Of 2,894 subjects in the analysis
      dataset, 38% were women; 71% were recruited in the United States and 29% in
      Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL)
      level > or =130 mg/dL and 124 of these (47%) were not on statin. Among those high
      risk persons on statin treatment, only 42% had an LDL < or =100 mg/dL. Subjects
      in the overall cohort were more likely to be on a statin if they were treated in
      the United States or had a history of hypertension or coronary artery disease.
      CONCLUSIONS: Approximately one out of three guideline-eligible high vascular risk
      ischemic stroke patients in this study had low-density lipoprotein cholesterol
      concentrations above qualifying levels for pharmacologic therapy, but half of
      these patients were not taking a statin, and of those receiving statin treatment,
      less than half were within recommended lipid goals.

PMID- 16636232
TI  - Is IV tissue plasminogen activator beneficial in patients with hyperdense artery
      sign?
AB  - OBJECTIVE: To evaluate the effect of IV recombinant tissue plasminogen activator
      (rt-PA) in patients with hyperdense artery sign (HAS) on initial CT scan.
      METHODS: The authors determined the differential effect of IV rt-PA (0.9 mg/kg)
      in patients with HAS by testing the interaction of rt-PA and HAS in a logistic
      regression model after adjusting for age, sex, initial NIH Stroke Scale score
      (NIHSSS), time to randomization, systolic blood pressure, serum glucose, body
      temperature, and rt-PA in 616 patients treated within 3 hours of symptom onset.
      Outcomes evaluated included intracranial hemorrhage, modified Rankin scale (mRS)
      0-1, Barthel Index (BI) of > or = 95, Glasgow Outcome Scale (GOS) of 0-1, NIHSSS
      0-1, and death at 90 days. RESULTS: HAS was detected on the initial CT scan in 91
      (15%) of the 616 patients by an independent neuroradiologist. Significantly lower
      rates of mRS 0-1, BI > or = 95, GOS of 0-1, or NIHSSS 0-1 at 90 days were
      observed among patients with HAS. IV rt-PA significantly increased the rates of
      mRS 0-1, BI > or = 95, GOS of 0-1, or NIHSSS 0-1 at 90 days after adjusting for
      potential confounders without any significant modifying effect (interaction) of
      HAS. Among the 91 patients with HAS, rt-PA use demonstrated a trend or
      significance for increased adjusted rates of favorable outcomes by mRS (p =
      0.04), BI (p = 0.1), GOS (p = 0.03), and NIHSSS (p = 0.01). CONCLUSION: Although
      hyperdense artery sign is associated with poor outcome, IV recombinant tissue
      plasminogen activator may be beneficial in this subgroup of patients with
      ischemic stroke.

PMID- 16636233
TI  - Hematoma growth is a determinant of mortality and poor outcome after
      intracerebral hemorrhage.
AB  - BACKGROUND: Although volume of intracerebral hemorrhage (ICH) is a predictor of
      mortality, it is unknown whether subsequent hematoma growth further increases the
      risk of death or poor functional outcome. METHODS: To determine if hematoma
      growth independently predicts poor outcome, the authors performed an individual
      meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset
      and 24-hour follow-up. Placebo patients were pooled from three trials
      investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients
      from the Cincinnati study (total 218). Other baseline factors included age,
      gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular
      hemorrhage (IVH), and location. RESULTS: Overall, 72.9% of patients exhibited
      some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR]
      1.05 per 10% increase [95% CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR
      1.01 per mL [95% CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95% CI: 0.81, 0.96; p
      = 0.003]), and IVH (HR 2.23 [95% CI: 1.25, 3.98; p = 0.007]) were all associated
      with increased mortality. Percentage growth (cumulative OR 0.84 [95% CI: 0.75,
      0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95% CI: 0.91, 0.97; p
      < 0.0001]), GCS (cumulative OR 1.46 [95% CI: 1.21, 1.82; p < 0.0001]), and age
      (cumulative OR 0.95 [95% CI: 0.92, 0.98; p = 0.0009]) predicted outcome modified
      Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict
      outcomes. CONCLUSIONS: Hematoma growth is an independent determinant of both
      mortality and functional outcome after intracerebral hemorrhage. Attenuation of
      growth is an important therapeutic strategy.

PMID- 16636234
TI  - Long-term mortality after intracerebral hemorrhage.
AB  - OBJECTIVE: To characterize long-term mortality following intracerebral hemorrhage
      (ICH) in two large population-based cohorts assembled more than a decade apart.
      METHODS: All patients age > or = 18 hospitalized with nontraumatic ICH in the
      Greater Cincinnati/Northern Kentucky area were identified during 1988 (Cohort 1)
      and from May 1998 to July 2001 and August 2002 to April 2003 (Cohort 2).
      Mortality was tabulated using actuarial methods and compared with a log-rank
      test. RESULTS: There were 183 patients with ICH in Cohort 1 and 1,041 patients in
      Cohort 2. Patients in Cohort 1 were more likely to be white (p = 0.024) and
      undergo operation for their ICH (p = 0.002), whereas patients in Cohort 2 were
      more commonly on anticoagulants (p < 0.001). Among patients in Cohort 1,
      mortality at 7 days, 1 year, and 10 years was 31, 59, and 82%. Among patients in
      Cohort 2, mortality at 7 days and 1 year was 34 and 53%. Mortality rates did not
      differ between cohorts by log-rank test (p = 0.259). CONCLUSIONS: Intracerebral
      hemorrhage (ICH) mortality did not improve significantly between study periods.
      Operation for ICH became less frequent, whereas anticoagulant-associated ICH
      became more common.

PMID- 16636235
TI  - Asymptomatic sinovenous thrombosis in a healthy neonate.

PMID- 16636236
TI  - Prospective study of symptomatic atherothrombotic intracranial stenoses: the
      GESICA study.
AB  - BACKGROUND: Symptomatic intracranial atherothrombotic stenoses (ICAS) are
      associated with high rates of cerebrovascular ischemic events. OBJECTIVE: To
      conduct a prospective multicenter study to evaluate the natural history of ICAS
      and, in those patients refractory to medical treatment, the outcomes associated
      with intracranial angioplasty. METHODS: Patients aged 18 to 80 were enrolled with
      symptoms attributed to a single ICAS of > or =50%. Optimal medical therapy of
      vascular risk factors and preventive antithrombotic therapy were at the
      discretion of the local investigator. Patients were eligible for intracranial
      angioplasty after experiencing recurrent stroke despite medical therapy.
      Neurologic and ultrasonographic examinations were performed at study inclusion, 3
      months after enrollment, and every 6 months of follow-up thereafter, for 36
      months. RESULTS: One hundred two patients were included, with a mean age of 63.3
      +/- 10.4 years. Intracranial artery stenoses involved the vertebral artery in
      22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the
      internal carotid artery in 25.5%. In 27.4% of the patients, the stenoses had
      clinical hemodynamic characteristics. During a mean follow-up of 23.4 months,
      38.2% of the patients had a cerebrovascular event: ischemic stroke in 13.7% and
      TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7%
      had a recurrent stroke or TIA in the territory of the stenotic artery; this
      association was significant in univariate analysis. Twenty-eight patients
      underwent an endovascular procedure with a neurologic periprocedural complication
      rate of 14.2%. The overall vascular death rate was 8.8%. CONCLUSIONS: Despite
      medical treatment, the 2-year recurrence rate of ischemic events in the territory
      of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6% of
      patients. Clinically significant hemodynamic stenoses were associated with stroke
      recurrence and may help identify a high risk subset of patients.

PMID- 16636237
TI  - Normalizing motor-related brain activity: subthalamic nucleus stimulation in
      Parkinson disease.
AB  - OBJECTIVE: To test whether therapeutic unilateral deep brain stimulation (DBS) of
      the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to
      normalization in the pattern of brain activation during movement execution and
      control of movement extent. METHODS: Six patients with PD were imaged off
      medication by PET during performance of a visually guided tracking task with the
      DBS voltage programmed for therapeutic (effective) or subtherapeutic
      (ineffective) stimulation. Data from patients with PD during ineffective
      stimulation were compared with a group of 13 age-matched control subjects to
      identify sites with abnormal patterns of activation. Conjunction analysis was
      used to identify those areas in patients with PD where activity normalized when
      they were treated with effective stimulation. RESULTS: For movement execution,
      effective DBS caused an increase of activation in the supplementary motor area
      (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At
      rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation
      also induced reductions of movement related "overactivity" compared with healthy
      subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent
      with the notion that many areas are recruited to compensate for ineffective motor
      initiation. Normalization of activity related to the control of movement extent
      was associated with reductions of activity in primary motor cortex, SMA, and
      basal ganglia. CONCLUSIONS: Effective subthalamic nucleus stimulation leads to
      task-specific modifications with appropriate recruitment of motor areas as well
      as widespread, nonspecific reductions of compensatory or competing cortical
      activity.

PMID- 16636238
TI  - Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.
AB  - BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by
      onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy,
      oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels.
      Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To
      describe the clinical features of AOA2 and to identify the SETX mutations in 10
      patients from four Italian families. METHODS: The patients underwent clinical
      examination, routine laboratory tests, nerve conduction studies, sural nerve
      biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the
      patients had cerebellar features, including limb and truncal ataxia, and slurred
      speech. OMA was observed in two patients, extrapyramidal symptoms in two, and
      mental impairment in three. High serum AFP levels, motor and sensory axonal
      neuropathy, and marked cerebellar atrophy on MRI were detected in all the
      patients who underwent these examinations. Sural nerve biopsy revealed a severe
      depletion of large myelinated fibers in one patient, and both large and small
      myelinated fibers in another. Postmortem findings are also reported in one of the
      patients. Four different homozygous SETX mutations were found (a large-scale
      deletion, a missense change, a single-base deletion, and a splice-site mutation).
      CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly
      homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant
      finding. The identification of new mutations expands the array of SETX variants,
      and the finding of a missense change outside the helicase domain suggests the
      existence of at least one more functional region in the N-terminus of senataxin.

PMID- 16636239
TI  - The effect of noninvasive ventilation on ALS patients and their caregivers.
AB  - BACKGROUND: Noninvasive ventilation (NIV) reduces mortality and improves some
      aspects of quality of life (QoL) in ALS. However, concerns remain that
      progressive disability may negate these benefits and unnecessarily burden
      caregivers. METHODS: Thirty-nine patients requiring NIV were offered treatment.
      Twenty-six were established on NIV, but 13 declined or could not tolerate NIV.
      Fifteen patients without respiratory muscle weakness (RMW) but with similar ALS
      severity and age were studied in parallel. Caregivers of 21 NIV, 7 untreated, and
      10 patients without RMW participated. Patients and caregivers had detailed QoL
      measurements for 12 months. NIV patients underwent cognitive testing before and
      after treatment. RESULTS: RMW correlated with lower QoL. The median survival of
      untreated patients (18 days; 95% CI 11 to 25 days) was shorter than for NIV
      patients (298 days; 95% CI 192 to 404 days) and non-RMW patients (370 days; 95%
      CI 278 to 462 days; log rank test [2 df] = 81, p = 0.00001). A wide range of QoL
      measures improved within 1 month of starting NIV, and improvements were
      maintained for 12 months. QoL of non-RMW patients declined as RMW progressed.
      Caregivers of NIV and non-RMW patients showed similar increases in burden, but
      NIV patient caregivers developed a deterioration in the Short Form-36 Vitality
      score. No improvements were found on measures of learning and recall in the NIV
      patients. CONCLUSIONS: Respiratory muscle weakness has a greater impact on
      quality of life (QoL) than overall ALS severity. Noninvasive ventilation (NIV)
      improves QoL despite ALS progression. NIV has no impact on most aspects of
      caregiver QoL and does not significantly increase caregiver burden or stress.

PMID- 16636240
TI  - A novel locus for hereditary spastic paraplegia with thin corpus callosum and
      epilepsy.
AB  - BACKGROUND: Hereditary spastic paraplegia (HSP) are classified clinically as pure
      when progressive spasticity occurs in isolation or complicated when other
      neurologic abnormalities are present. At least 22 genetic loci have been linked
      to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the
      presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One
      genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC,
      but some HSP-TCC families have not been linked to this locus. METHODS: The
      authors characterized two families clinically and radiologically and performed a
      genome-wide scan and linkage analysis. RESULTS: The two families had complicated
      ARHSP. The affected individuals in Family A had thin corpus callosum and mental
      retardation, whereas in Family B two of three affected individuals had epilepsy.
      In both families linkage analysis identified a locus on chromosome 8 between
      markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker
      D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for
      ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are
      interesting functional candidate genes for this HSP form. CONCLUSION: Two
      consanguineous families with complicated autosomal recessive hereditary spastic
      paraplegia were clinically characterized and genetically mapped to a new locus on
      8p12-p11.21.

PMID- 16636241
TI  - Does multiple sclerosis-associated disability differ between races?
AB  - OBJECTIVE: To investigate differences in disability between African American and
      Caucasian patients with multiple sclerosis (MS) by comparing the relationship
      between current age and disability between races and by assessing the effect of
      adjustment for socioeconomic status (SES) on the associations. METHODS: The
      authors selected US participants from the North American Research Committee on
      Multiple Sclerosis (NARCOMS) Registry with an age at symptom onset of 10 to 60
      years, who reported their race as Caucasian or African American (n = 21,557).
      They classified participants as having mild, moderate, or severe disability in
      the domains of mobility, hand function, cognition, and vision using Patient
      Determined Disease Steps and Performance Scales and assessed the association of
      disability with race using polytomous logistic regression. RESULTS: Disability
      increased more rapidly with increasing disease duration in older patients, but
      there was no interaction between race and age. African Americans had increased
      odds of severe vs mild disability in all four domains (odds ratio [OR] [95% CI]:
      hand 1.35 [1.10 to 1.64]; vision 1.75 [1.37 to 2.27]; cognition 1.32 [1.04 to
      1.67]; mobility 1.32 [1.11 to 1.56]). Adjustment for all covariates, including
      SES, attenuated these associations (OR [95% CI]: hand 1.27 [1.00 to 1.61]; vision
      1.59 [1.19 to 2.08]; cognition 0.98 [0.74 to 1.30]; mobility 1.37 [1.11 to
      1.67]). Lack of adjustment for SES produced stronger associations. After
      enrollment in NARCOMS, disability progression did not differ between the groups.
      CONCLUSIONS: African Americans experience greater multiple sclerosis-associated
      disability than Caucasians. Failure to account for socioeconomic status leads to
      overestimation of these differences. Disease progression is similar in African
      Americans and Caucasians after diagnosis.

PMID- 16636242
TI  - Weir Mitchell's observations on sensory localization and their influence on
      Jacksonian neurology.
AB  - BACKGROUND: John Hughlings Jackson (1835-1911) in London was critical in
      advancing the concept of cerebral localization. Hughlings Jackson, however, did
      not work in a vacuum. Silas Weir Mitchell (1829-1914), in Philadelphia, published
      several clinical observations related to localization. OBJECTIVE: To examine Weir
      Mitchell's clinical observations on sensory localization, to determine whether
      they influenced Jacksonian neurology, and to elucidate the private relationship
      between the two men. METHODS: The authors reviewed published (fictional and
      scientific writings of Weir Mitchell and scientific writings of Hughlings
      Jackson) and archival sources (Weir Mitchell's unpublished autobiography and
      Hughlings Jackson's unpublished correspondence with Weir Mitchell). RESULTS: In
      the 1860s, Weir Mitchell, through his work on phantom limb syndrome and other
      nerve injuries, made oblique references to the central representation of body
      parts, specifically with regard to sensation. Hughlings Jackson had an interest
      in somatotopic representation in the nervous system and repeatedly cited Weir
      Mitchell's work in support of his ideas. The two shared several patients, met at
      least once in London, and carried on a friendly correspondence. CONCLUSIONS: Weir
      Mitchell's observations on sensory localization were well known to Hughlings
      Jackson, who cited them in seminal articles on cortical localization. Their
      correspondence provides an example of trans-Atlantic scientific and clinical
      communication at the time that neurology emerged as a distinct clinical
      discipline.

PMID- 16636243
TI  - Mycophenolate mofetil in dermatomyositis: is it safe?
AB  - The authors report 10 patients with idiopathic dermatomyositis treated with
      mycophenolate mofetil in combination with corticosteroids. Successful steroid
      taper without disease relapse was achieved in six patients; however, in three
      patients, treatment was associated with opportunistic infections, leading to
      death in one patient. The disproportionately high rate of opportunistic
      infections in this group is considered.

PMID- 16636244
TI  - Clinical characteristics of myotonic dystrophy type 1 patients with small CTG
      expansions.
AB  - The authors report a genotype-phenotype correlation study in 102 patients with
      myotonic dystrophy type 1 carrying small CTG repeat expansions. Most patients
      carrying 50 to 99 CTG repeats were asymptomatic, except for cataracts. Myotonia,
      weakness, excessive daytime sleepiness, and myotonic discharges at EMG were
      significantly more present in the patients with 100 to 200 CTG repeats. These
      findings highlight different outcomes related to the expansion size, even among
      small CTG expansions.

PMID- 16636245
TI  - New HSN2 mutation in Japanese patient with hereditary sensory and autonomic
      neuropathy type 2.
AB  - The authors report a Japanese patient with hereditary sensory and autonomic
      neuropathy type 2 (HSAN2) who has a new mutation of the HSN2 gene. The pathologic
      findings of the patient matched those of Canadian patients. They identified a
      homozygous 1134-1135 ins T mutation, resulting in a frameshift, and the
      subsequent premature stop codon at residue 378. These observations support the
      hypothesis that HSN2 is a causative gene for HSAN2.

PMID- 16636246
TI  - Annexin V SPECT imaging of phosphatidylserine expression in patients with
      dementia.
AB  - The authors sought to use radiolabeled annexin V, a marker of phosphatidylserine
      expression, to image Alzheimer dementia (AD). Four of five patients with AD had
      multifocal cortical annexin V uptake, whereas all seven non-AD and six control
      patients had normal SPECT. The mean cortex/cerebellar activity in patients with
      AD (1.4 +/- 0.6) was higher than that of non-AD dementia patients (0.7 +/- 0.2; p
      = 0.02). Radiolabeled annexin V may be useful for imaging AD.

PMID- 16636247
TI  - Monocyte chemoattractant protein-1 correlates with subcortical brain injury in
      HIV infection.
AB  - Various biomarkers have been suggested as associative or predictive of HIV
      associated neurocognitive impairment. Plasma levels of monocyte chemoattractant
      protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and hematocrit were
      evaluated for relationships with diffusion tensor imaging measurements of centrum
      semiovale, caudate, and putamen. MCP-1 levels correlated with tissue status (mean
      diffusivity) in all examined regions. Plasma markers were also significantly
      correlated with anisotropy measurements in centrum semiovale (TNF-alpha) and
      putamen (hematocrit).

PMID- 16636248
TI  - MRI in patients with high-grade gliomas treated with bevacizumab and
      chemotherapy.
AB  - Patients with recurrent gliomas (n = 14) were treated with bevacizumab and
      carboplatin, cpt-11, or etoposide. Follow-up MRI scans were obtained 2 to 6 weeks
      after initiation of treatment. Contrast-enhancing tumor shrank in 7 patients,
      with reductions evident in as little as 2 weeks after initiation of therapy.
      Treatment seemed more effective for heterogeneously enhancing tumor compared with
      solidly enhancing tumor.

PMID- 16636249
TI  - Nonconvulsive status epilepticus in metastatic CNS disease.
AB  - The authors describe the clinical and diagnostic characteristics of four patients
      with metastatic CNS disease presenting in de novo nonconvulsive status
      epilepticus (NCSE). Treatment with anticonvulsants resulted in resolution of NCSE
      in two patients and a brief improvement in mental status in the other two
      patients. NCSE should be considered in the differential diagnosis of acute mental
      status change in patients with metastatic CNS disease.

PMID- 16636250
TI  - Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy.
AB  - The authors used 1H-MRS to investigate hypothalamic metabolism in 26 patients
      with cluster headache (CH) and 12 healthy subjects. Hypothalamic N
      acetylaspartate/creatine was reduced in patients with CH vs controls (p < 0.01).
      Dividing the patients into episodic CH outside- and in-cluster periods and
      chronic CH, the hypothalamic N-acetylaspartate/creatine in all three subgroups of
      patients was reduced. The reduction of the neuronal marker N-acetylaspartate is
      consistent with hypothalamic neuronal dysfunction in patients with CH.

PMID- 16636251
TI  - White matter damage in neonatal enterovirus meningoencephalitis.
AB  - The authors report six neonates with enteroviral meningoencephalitis. Five
      infants presented with prolonged seizures, and one presented with systemic
      enteroviral disease. Cranial ultrasonography showed increased echogenicity in the
      periventricular white matter, and MRI confirmed mild to severe white matter
      damage in all infants, which looked similar to periventricular leukomalacia. Two
      infants developed cerebral palsy: one was neurologically suspect at age 18
      months, and three were developmentally normal.

PMID- 16636252
TI  - Magnetic source imaging localizes epileptogenic zone in children with tuberous
      sclerosis complex.
AB  - The authors assessed whether magnetoencephalography/magnetic source imaging
      (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis
      complex (TSC). In six TSC children with focal seizures, ictal video-EEG predicted
      the region of resection with 56% sensitivity, 80% specificity, and 77% accuracy
      (p = 0.02), whereas interictal MEG/MSI fared better (100%, 94%, and 95%,
      respectively; p < 0.0001). Interictal MEG/MSI seems to identify epileptogenic
      zones more accurately in children with TSC and focal intractable epilepsy.

PMID- 16636253
TI  - The ICAM-1 E469K gene polymorphism is a risk factor for spontaneous cervical
      artery dissection.
AB  - In a primary study on proinflammatory genetic profiles in stroke, the authors
      found the E469K polymorphism of the intercellular adhesion molecule 1 (ICAM-1)
      highly represented in the subgroup with spontaneous cervical artery dissection
      (sCAD). They further investigated the same genetic variant in a second group of
      65 patients with sCAD. An association between sCAD and EE genotype was confirmed
      (odds ratio 3.16; p < 0.01), indicating that a proinflammatory predisposition is
      a risk factor for sCAD.

PMID- 16636254
TI  - Brain acetylcholinesterase activity in FTDP-17 studied by PET.

PMID- 16636255
TI  - Trichotillomania: an NREM sleep parasomnia?

PMID- 16636256
TI  - REM sleep behavior disorder initiated by acute brainstem multiple sclerosis.

PMID- 16636257
TI  - Differential effects of left and right hemispheric seizure onset on heart rate.

PMID- 16636258
TI  - Increase in multiple sclerosis relapse rate following in vitro fertilization.

PMID- 16636259
TI  - The prosecutor.

PMID- 16636260
TI  - Bilateral involvement of a single cranial nerve: analysis of 578 cases.

PMID- 16636261
TI  - The spectrum of presentations of venous infarction caused by deep cerebral vein
      thrombosis.

PMID- 16636262
TI  - Camptocormia: pathogenesis, classification, and response to therapy.

PMID- 16636263
TI  - Addendum to assessment: prevention of post-lumbar puncture headaches: report of
      the TTAS of the AAN.

PMID- 16636264
TI  - Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and
      cortical lesions.

PMID- 16636265
TI  - Use of serum prolactin in diagnosing epileptic seizures: report of the
      Therapeutics and Technology Assessment Subcommittee of the American Academy of
      Neurology.

PMID- 16636266
TI  - Primary central nervous system lymphomas (PCNSL): MRI response criteria revised.

PMID- 16636268
TI  - Dual targeting of a single tRNA(Trp) requires two different tryptophanyl-tRNA
      synthetases in Trypanosoma brucei.
AB  - The mitochondrion of Trypanosoma brucei does not encode any tRNAs. This
      deficiency is compensated for by the import of a small fraction of nearly all of
      its cytosolic tRNAs. Most trypanosomal aminoacyl-tRNA synthetases are encoded by
      single-copy genes, suggesting the use of the same enzyme in the cytosol and
      mitochondrion. However, the T. brucei genome contains two distinct genes for
      eukaryotic tryptophanyl-tRNA synthetase (TrpRS). RNA interference analysis
      established that both TrpRS1 and TrpRS2 are essential for growth and required for
      cytosolic and mitochondrial tryptophanyl-tRNA formation, respectively. Decoding
      the mitochondrial tryptophan codon UGA requires mitochondria-specific C-->U RNA
      editing in the anticodon of the imported tRNA(Trp). In vitro charging assays with
      recombinant TrpRS enzymes demonstrated that the edited anticodon and the
      mitochondria-specific thiolation of U33 in the imported tRNA(Trp) act as
      antideterminants for the cytosolic TrpRS1. The existence of two TrpRS enzymes,
      therefore, can be explained by the need for a mitochondrial synthetase with
      extended substrate specificity to achieve aminoacylation of the imported
      thiolated and edited tRNA(Trp). Thus, the notion that, in an organism, all
      nuclear-encoded tRNAs assigned to a given amino acid are charged by a single
      aminoacyl-tRNA synthetase, is not universally valid.

PMID- 16636269
TI  - Electron microscopic structure of purified, active gamma-secretase reveals an
      aqueous intramembrane chamber and two pores.
AB  - Gamma-secretase is an intramembrane-cleaving aspartyl protease required for the
      normal development of metazoans because it processes Notch within cellular
      membranes to release its signaling domain. More than two dozen additional
      substrates of diverse functions have been reported, including the Notch ligands
      Delta and Jagged, N- and E-cadherins, and a sodium channel subunit. The protease
      is causally implicated in Alzheimer's disease because it releases the neurotoxic
      amyloid beta-peptide (Abeta) from its precursor, APP. Gamma-secretase occurs as a
      large complex containing presenilin (bearing the active site aspartates),
      nicastrin, Aph-1, and Pen-2. Because the complex contains at least 18
      transmembrane domains, crystallographic approaches to its structure are difficult
      and remote. We recently purified the human complex essentially to homogeneity
      from stably expressing mammalian cells. Here, we use EM and single-particle image
      analysis on the purified enzyme, which produces physiological ratios of Abeta40
      and Abeta42, to obtain structural information on an intramembrane protease. The
      3D EM structure revealed a large, cylindrical interior chamber of approximately
      20-40 A in length, consistent with a proteinaceous proteolytic site that is
      occluded from the hydrophobic environment of the lipid bilayer. Lectin tagging of
      the nicastrin ectodomain enabled proper orientation of the globular,
      approximately 120-A-long complex within the membrane and revealed approximately
      20-A pores at the top and bottom that provide potential exit ports for cleavage
      products to the extra- and intracellular compartments. Our reconstructed 3D map
      provides a physical basis for hydrolysis of transmembrane substrates within a
      lipid bilayer and release of the products into distinct subcellular compartments.

PMID- 16636270
TI  - Immune dysregulation accelerates atherosclerosis and modulates plaque composition
      in systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) have accelerated
      atherosclerosis. The underlying mechanisms are poorly understood, and
      investigations have been hampered by the absence of animal models that reflect
      the human condition of generalized atherosclerosis and lupus. We addressed this
      problem by transferring lupus susceptibility to low-density lipoprotein (LDL)
      receptor-deficient (LDLr-/-) mice, an established model of atherosclerosis,
      creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.Sle1.2.3
      congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively). LDLr.Sle
      mice developed a lupus-like disease characterized by production of double
      stranded DNA autoantibodies and renal disease. When fed a Western-type diet,
      LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The
      plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T cells
      than controls. LDLr.Sle mice also had increased activation of CD4+ T and B cells
      and significantly higher antibody to oxidized LDL and cardiolipin. Collectively,
      these studies demonstrate that the lupus-susceptible immune system enhances
      atherogenesis and modulates plaque composition.

PMID- 16636271
TI  - Apolipoprotein B is conformationally flexible but anchored at a triolein/water
      interface: a possible model for lipoprotein surfaces.
AB  - Apolipoprotein B (apoB) is one of a unique group of proteins that form and bind
      to fat droplets, stabilize the emulsified fat, and direct their metabolism. ApoB,
      secreted on lipoproteins (emulsions), remains bound during lipid metabolism yet
      exhibits conformational flexibility. It has amphipathic beta-strand (AbetaS)-rich
      domains and amphipathic alpha-helix (AalphaH)-rich domains. We showed that two
      consensus AbetaS peptides of apoB bound strongly to hydrophobic interfaces
      [triolein/water (TO/W) and dodecane/water], were elastic, and were not pushed off
      the interface when the surface was compressed. In contrast, an AalphaH peptide
      modeling helical parts of apoB was forced off the TO/W interface by compression
      and readsorbed when the interface was expanded. In this report, the surface
      behavior of apoB-100 was studied at the TO/W interface. Solubilized apoB lowered
      the interfacial tension of TO/W in a concentration-dependent fashion. At
      equilibrium tension, if the surface was compressed, part of apoB was pushed off
      but quickly readsorbed when the surface was expanded. Even when the surface area
      was compressed by approximately 55%, part of the apoB molecule remained bound.
      The maximum surface pressure that apoB could withstand without being partially
      ejected was 13 mN/m. ApoB showed high elasticity at the TO/W interface. Based on
      studies of the consensus AbetaS and AalphaH peptides, we suggest that AbetaSs
      anchor apoB and are its nonexchangeable motif, whereas its conformational
      flexibility arises from both the elastic nature of the AbetaS and the ability of
      AalphaH domains of the molecule to desorb and readsorb rapidly in response to
      surface pressure changes.

PMID- 16636272
TI  - Lung dysfunction causes systemic hypoxia in estrogen receptor beta knockout
      (ERbeta-/-) mice.
AB  - Estrogen receptor beta (ERbeta) is highly expressed in both type I and II
      pneumocytes as well as bronchiolar epithelial cells. ERalpha is not detectable in
      the adult lung. Lungs of adult female ERbeta knockout (ERbeta-/-) mice have
      already been reported to have fewer alveoli and reduced elastic recoil. In this
      article, we report that, by 5 months of age, there are large areas of unexpanded
      alveoli in lungs of both male and female ERbeta-/- mice. There is increased
      staining for collagen and, by EM, abnormal clusters of collagen fibers are seen
      in the alveolar septa of ERbeta-/- mice. Immunohistochemical analysis and Western
      blotting with lung membrane fractions of ERbeta-/- mice revealed down-regulation
      of caveolin-1, increased expression of membrane type-1 metalloproteinase, matrix
      metalloproteinase 2 (active form), and tissue inhibitors of metalloproteinases 2.
      Hypoxia, measured by immunohistochemical analysis for hypoxia-inducible factor
      1alpha and chemical adducts (with Hypoxyprobe), was evident in the heart, ventral
      prostate, periovarian sac, kidney, liver, and brain of ERbeta-/- mice under
      resting conditions. Furthermore, both male and female adult ERbeta-/- mice were
      reluctant to run on a treadmill and tissue hypoxia became very pronounced after
      exercise. We conclude that ERbeta is necessary for the maintenance of the
      extracellular matrix composition in the lung and loss of ERbeta leads to abnormal
      lung structure and systemic hypoxia. Systemic hypoxia may be responsible for the
      reported left and right heart ventricular hypertrophy and systemic hypertension
      in ERbeta-/- mice.

PMID- 16636273
TI  - Reducing the fitness cost of antibiotic resistance by amplification of initiator
      tRNA genes.
AB  - Deformylase inhibitors belong to a novel antibiotic class that targets peptide
      deformylase, a bacterial enzyme that removes the formyl group from N-terminal
      methionine in nascent polypeptides. Using the bacterium Salmonella enterica, we
      isolated mutants with resistance toward the peptide deformylase inhibitor
      actinonin. Resistance mutations were identified in two genes that are required
      for the formylation of methionyl (Met) initiator tRNA (tRNAi)(fMet): the fmt gene
      encoding the enzyme methionyl-tRNA formyltransferase and the folD gene encoding
      the bifunctional enzyme methylenetetrahydrofolate-dehydrogenase and 
      cyclohydrolase. In the absence of antibiotic, these resistance mutations
      conferred a fitness cost that was manifested as a reduced growth rate in
      laboratory medium and in mice. By serially passaging the low-fitness mutants in
      growth medium without antibiotic, the fitness costs could be partly ameliorated
      either by intragenic mutations in the fmt/folD genes or by extragenic
      compensatory mutations. Of the extragenically compensated fmt mutants,
      approximately one-third carried amplifications of the identical, tandemly
      repeated metZ and metW genes, encoding tRNAi. The increase in metZW gene copy
      number varied from 5- to 40-fold and was accompanied by a similar increase in
      tRNAi levels. The rise in tRNAi level compensated for the lack of methionyl-tRNA
      formyltransferase activity and allowed translation initiation to proceed with
      nonformylated methionyl tRNAi. Amplified units varied in size from 1.9 to 94 kbp.
      Suppression of deleterious mutations by gene amplification may be involved in the
      evolution of new gene functions.

PMID- 16636274
TI  - Disulfide cross-linked protein represents a significant fraction of ALS
      associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice.
AB  - Point mutations in Cu, Zn-superoxide dismutase (SOD1) cause a familial form of
      the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Aggregates of
      mutant SOD1 proteins are observed in histopathology and are invoked in several
      proposed mechanisms for motor neuronal death; however, the significant stability
      and activity of the mature mutant proteins are not readily explained in such
      models. Recent biochemical studies suggest that it is the immature disulfide
      reduced forms of the familial ALS mutant SOD1 proteins that play a critical role;
      these forms tend to misfold, oligomerize, and readily undergo incorrect disulfide
      formation upon mild oxidative stress in vitro. Here we provide physiological
      support for this mechanism of aggregate formation and show that a significant
      fraction of the insoluble SOD1 aggregates in spinal cord of the ALS-model
      transgenic mice contain multimers cross-linked via intermolecular disulfide
      bonds. These insoluble disulfide-linked SOD1 multimers are found only in the
      spinal cord of symptomatic transgenic animals, are not observed in unafflicted
      tissue such as brain cortex and liver, and can incorporate WT SOD1 protein. The
      findings provide a biochemical basis for a pathological hallmark of this disease;
      namely, incorrect disulfide cross-linking of the immature, misfolded mutant
      proteins leads to insoluble aggregates.

PMID- 16636275
TI  - Conversion to the amyotrophic lateral sclerosis phenotype is associated with
      intermolecular linked insoluble aggregates of SOD1 in mitochondria.
AB  - Twenty percent of the familial form of amyotrophic lateral sclerosis (ALS) is
      caused by mutations in the Cu, Zn-superoxide dismutase gene (SOD1) through the
      gain of a toxic function. The nature of this toxic function of mutant SOD1 has
      remained largely unknown. Here we show that WT SOD1 not only hastens onset of the
      ALS phenotype but can also convert an unaffected phenotype to an ALS phenotype in
      mutant SOD1 transgenic mouse models. Further analyses of the single- and double
      transgenic mice revealed that conversion of mutant SOD1 from a soluble form to an
      aggregated and detergent-insoluble form was associated with development of the
      ALS phenotype in transgenic mice. Conversion of WT SOD1 from a soluble form to an
      aggregated and insoluble form also correlates with exacerbation of the disease or
      conversion to a disease phenotype in double-transgenic mice. This conversion,
      observed in the mitochondrial fraction of the spinal cord, involved formation of
      insoluble SOD1 dimers and multimers that are crosslinked through intermolecular
      disulfide bonds via oxidation of cysteine residues in SOD1. Our data thus show a
      molecular mechanism by which SOD1, an important protein in cellular defense
      against free radicals, is converted to aggregated and apparently ALS-associated
      toxic dimers and multimers by redox processes. These findings provide evidence of
      direct links among oxidation, protein aggregation, mitochondrial damage, and SOD1
      mediated ALS, with possible applications to the aging process and other late
      onset neurodegenerative disorders. Importantly, rational therapy based on these
      observations can now be developed and tested.

PMID- 16636276
TI  - NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: genotype
      and sex interactions.
AB  - Because the transcription factor neuronal Per-Arnt-Sim-type signal-sensor protein
      domain protein 2 (NPAS2) acts both as a sensor and an effector of intracellular
      energy balance, and because sleep is thought to correct an energy imbalance
      incurred during waking, we examined NPAS2's role in sleep homeostasis using npas2
      knockout (npas2-/-) mice. We found that, under conditions of increased sleep
      need, i.e., at the end of the active period or after sleep deprivation (SD),
      NPAS2 allows for sleep to occur at times when mice are normally awake. Lack of
      npas2 affected electroencephalogram activity of thalamocortical origin; during
      non-rapid eye movement sleep (NREMS), activity in the spindle range (10-15 Hz)
      was reduced, and within the delta range (1-4 Hz), activity shifted toward faster
      frequencies. In addition, the increase in the cortical expression of the NPAS2
      target gene period2 (per2) after SD was attenuated in npas2-/- mice. This implies
      that NPAS2 importantly contributes to the previously documented wake-dependent
      increase in cortical per2 expression. The data also revealed numerous sex
      differences in sleep; in females, sleep need accumulated at a slower rate, and
      REMS loss was not recovered after SD. In contrast, the rebound in NREMS time
      after SD was compromised only in npas2-/- males. We conclude that NPAS2 plays a
      role in sleep homeostasis, most likely at the level of the thalamus and cortex,
      where NPAS2 is abundantly expressed.

PMID- 16636277
TI  - Insights into the serine protease mechanism from atomic resolution structures of
      trypsin reaction intermediates.
AB  - Atomic resolution structures of trypsin acyl-enzymes and a tetrahedral
      intermediate analog, along with previously solved structures representing the
      Michaelis complex, are used to reconstruct events in the catalytic cycle of this
      classic serine protease. Structural comparisons provide insight into active site
      adjustments involved in catalysis. Subtle motions of the catalytic serine and
      histidine residues coordinated with translation of the substrate reaction center
      are seen to favor the forward progress of the acylation reaction. The structures
      also clarify the attack trajectory of the hydrolytic water in the deacylation
      reaction.

PMID- 16636278
TI  - Good old-fashioned (anti)sense.

PMID- 16636279
TI  - An electronic time scale in chemistry.
AB  - Ultrafast, subfemtosecond charge migration in small peptides is discussed on the
      basis of computational studies and compared with the selective bond dissociation
      after ionization as observed by Schlag and Weinkauf. The reported relaxation
      could be probed in real time if the removal of an electron could be achieved on
      the attosecond time scale. Then the mean field seen by an electron would be
      changing rapidly enough to initiate the migration. Tyrosine-terminated
      tetrapeptides have a particularly fast charge migration where in <1 fs the charge
      arrives at the other end. A femtosecond pulse can be used to observe the somewhat
      slower relaxation induced by correlation between electrons of different spins. A
      slower relaxation also is indicated when removing a deeper-lying valence
      electron. When a chromophoric amino acid is at one end of the peptide, the charge
      can migrate all along the peptide backbone up to the N end, but site-selective
      ionization is probably easier to detect for tryptophan than for tyrosine.

PMID- 16636280
TI  - Time, temperature, and load: the flaws of carbon nanotubes.

PMID- 16636281
TI  - Nuclear spin noise imaging.
AB  - NMR images were obtained from the proton spin noise signals of a water-containing
      phantom, which was placed in the highly tuned, low-noise resonant circuit of a
      cryogenically cooled NMR probe in the presence of systematically varied magnetic
      field gradients. The spatially resolved proton spin density was obtained from the
      raw signal by a modified projection-reconstruction protocol. Although spin noise
      imaging is inherently less sensitive than conventional magnetic resonance
      imaging, it affords an entirely noninvasive visualization of the interior of
      opaque objects or subjects. Thus, tomography becomes possible even when neither x
      ray nor radio frequency radiation can be applied for technical or safety reasons.

PMID- 16636282
TI  - Highly conserved syntenic blocks at the vertebrate Hox loci and conserved
      regulatory elements within and outside Hox gene clusters.
AB  - Hox genes in vertebrates are clustered, and the organization of the clusters has
      been highly conserved during evolution. The conservation of Hox clusters has been
      attributed to enhancers located within and outside the Hox clusters that are
      essential for the coordinated "temporal" and "spatial" expression patterns of Hox
      genes in developing embryos. To identify evolutionarily conserved regulatory
      elements within and outside the Hox clusters, we obtained contiguous sequences
      for the conserved syntenic blocks from the seven Hox loci in fugu and carried out
      a systematic search for conserved noncoding sequences (CNS) in the human, mouse,
      and fugu Hox loci. Our analysis has uncovered unusually large conserved syntenic
      blocks at the HoxA and HoxD loci. The conserved syntenic blocks at the human and
      mouse HoxA and HoxD loci span 5.4 Mb and 4 Mb and contain 21 and 19 genes,
      respectively. The corresponding regions in fugu are 16- and 12-fold smaller. A
      large number of CNS was identified within the Hox clusters and outside the Hox
      clusters spread over large regions. The CNS include previously characterized
      enhancers and overlap with the 5' global control regions of HoxA and HoxD
      clusters. Most of the CNS are likely to be control regions involved in the
      regulation of Hox and other genes in these loci. We propose that the regulatory
      elements spread across large regions on either side of Hox clusters are a major
      evolutionary constraint that has maintained the exceptionally long syntenic
      blocks at the HoxA and HoxD loci.

PMID- 16636283
TI  - Stably tethered multifunctional structures of defined composition made by the
      dock and lock method for use in cancer targeting.
AB  - We describe a platform technology, termed the dock and lock method, which uses a
      natural binding between the regulatory subunits of cAMP-dependent protein kinase
      and the anchoring domains of A kinase anchor proteins for general application in
      constructing bioactive conjugates of different protein and nonprotein molecules
      from modular subunits on demand. This approach could allow quantitative and site
      specific coupling of many different biological substances for diverse medical
      applications. The dock and lock method is validated herein by producing
      bispecific, trivalent-binding complexes composed of three stably linked Fab
      fragments capable of selective delivery of radiotracers to human cancer
      xenografts, resulting in rapid, significantly improved cancer targeting and
      imaging, providing tumor/blood ratios from 66 +/- 5 at 1 h to 395 +/- 26 at 24 h.

PMID- 16636284
TI  - An internal antisense RNA regulates expression of the photosynthesis gene isiA.
AB  - Small regulatory noncoding RNAs exist in both eukaryotic and prokaryotic
      organisms. Most of these RNA transcripts are trans-encoded RNAs with short and
      only partial antisense complementarity to their target RNAs, which regulate gene
      expression by modifying mRNA stability and translation. In contrast, reports on
      the function of cis-encoded, perfectly complementary antisense RNAs in eubacteria
      are rare. Cyanobacteria respond to iron deficiency by expressing IsiA (iron
      stress-induced protein A), which forms a giant ring structure around photosystem
      I. Here, we show that this process is controlled by IsrR (iron stress-repressed
      RNA), a cis-encoded antisense RNA transcribed from the isiA noncoding strand.
      Artificial overexpression of IsrR under iron stress causes a strongly diminished
      number of IsiA-photosystem I supercomplexes, whereas IsrR depletion results in
      premature expression of IsiA. The coupled degradation of IsrR/isiA mRNA duplexes
      appears to be a reversible switch that can respond to environmental changes. IsrR
      is the only RNA known so far to regulate a photosynthesis component.

PMID- 16636285
TI  - Desensitization of mechano-gated K2P channels.
AB  - The neuronal mechano-gated K2P channels TREK-1 and TRAAK show pronounced
      desensitization within 100 ms of membrane stretch. Desensitization persists in
      the presence of cytoskeleton disrupting agents, upon patch excision, and when
      channels are expressed in membrane blebs. Mechanosensitive currents evoked with a
      variety of complex stimulus protocols were globally fit to a four-state cyclic
      kinetic model in detailed balance, without the need to introduce adaptation of
      the stimulus. However, we show that patch stress can be a complex function of
      time and stimulation history. The kinetic model couples desensitization to
      activation, so that gentle conditioning stimuli do not cause desensitization.
      Prestressing the channels with pressure, amphipaths, intracellular acidosis, or
      the E306A mutation reduces the peak-to-steady-state ratio by changing the
      preexponential terms of the rate constants, increasing the steady-state current
      amplitude. The mechanical responsivity can be accounted for by a change of in
      plane area of approximately 2 nm2 between the closed and open conformations.
      Desensitization and its regulation by chemical messengers is predicted to
      condition the physiological role of K2P channels.

PMID- 16636286
TI  - A yeast assay probes the interaction between botulinum neurotoxin serotype B and
      its SNARE substrate.
AB  - The seven functionally distinct serotypes (A-G) of botulinum neurotoxin (BoNT)
      are dichains consisting of light chain (LC) with zinc-dependent endoprotease
      activity connected by one disulfide bond to heavy chain with neuronal-cell
      translocation and receptor-binding domains. LC-mediated proteolysis of soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and
      consequent inhibition of synaptic vesicle fusion to the presynaptic membrane of
      human motor neurons are responsible for flaccid paralysis associated with
      botulism. LC endoproteolysis is complex, requiring highly extended SNARE
      sequences at the surface of intracellular membranes and prompting our development
      of a genetically amenable assay to monitor the interaction between BoNT/LC and
      its SNARE substrate. Using BoNT serotype B as a model, the assay employs a
      chimeric SNARE protein where a portion of neuronal synaptobrevin (Sb) is fused to
      Snc2p, a Sb ortholog required for protein secretion from yeast cells. Regulated
      expression of serotype B-LC in yeast leads to cleavage of the chimera and a
      conditional growth defect. To assess utility of this assay for monitoring SNARE
      protein cleavage, we growth-selected chimeric SNARE mutations that inhibited
      proteolysis. When these mutations were introduced into Sb and examined for
      cleavage, substrate residues located near and distal to the cleavage site were
      important, including residues positioned near the Sb transmembrane domain, an
      unexplored aspect of BoNT cell intoxication. Additional mutations were positioned
      in a nine-residue SNARE motif, supporting a previously assigned role for this
      motif in LC recognition and providing proof of principle for the application of
      yeast-based technology to study intracellular BoNT/LC endoproteases.

PMID- 16636287
TI  - Molecular genetic anatomy of inter- and intraserotype variation in the human
      bacterial pathogen group A Streptococcus.
AB  - In recent years we have studied the relationship between strain genotypes and
      patient phenotypes in group A Streptococcus (GAS), a model human bacterial
      pathogen that causes extensive morbidity and mortality worldwide. We have
      concentrated our efforts on serotype M3 organisms because these strains are
      common causes of pharyngeal and invasive infections, produce unusually severe
      invasive infections, and can exhibit epidemic behavior. Our studies have been
      hindered by the lack of genome-scale phylogenies of multiple GAS strains and
      whole-genome sequences of multiple serotype M3 strains recovered from individuals
      with defined clinical phenotypes. To remove some of these impediments, we
      sequenced to closure the genome of four additional GAS strains and conducted
      comparative genomic resequencing of 12 contemporary serotype M3 strains
      representing distinct genotypes and phenotypes. Serotype M3 strains are a single
      phylogenetic lineage. Strains from asymptomatic throat carriers were
      significantly less virulent for mice than sterile-site isolates and evolved to a
      less virulent phenotype by multiple genetic pathways. Strain persistence or
      extinction between epidemics was strongly associated with presence or absence,
      respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A
      serotype M3 clone significantly underrepresented among necrotizing fasciitis
      cases has a unique frameshift mutation that truncates MtsR, a transcriptional
      regulator controlling expression of genes encoding iron-acquisition proteins.
      Expression microarray analysis of this clone confirmed significant alteration in
      expression of genes encoding iron metabolism proteins. Our analysis provided
      unprecedented detail about the molecular anatomy of bacterial strain genotype
      patient phenotype relationships.

PMID- 16636288
TI  - Sleep after spatial learning promotes covert reorganization of brain activity.
AB  - Sleep promotes the integration of recently acquired spatial memories into
      cerebral networks for the long term. In this study, we examined how sleep
      deprivation hinders this consolidation process. Using functional MRI, we mapped
      regional cerebral activity during place-finding navigation in a virtual town,
      immediately after learning and 3 days later, in subjects either allowed regular
      sleep (RS) or totally sleep-deprived (TSD) on the first posttraining night. At
      immediate and delayed retrieval, place-finding navigation elicited increased
      brain activity in an extended hippocampo-neocortical network in both RS and TSD
      subjects. Behavioral performance was equivalent between groups. However, striatal
      navigation-related activity increased more at delayed retrieval in RS than in TSD
      subjects. Furthermore, correlations between striatal response and behavioral
      performance, as well as functional connectivity between the striatum and the
      hippocampus, were modulated by posttraining sleep. These data suggest that brain
      activity is restructured during sleep in such a way that navigation in the
      virtual environment, initially related to a hippocampus-dependent spatial
      strategy, becomes progressively contingent in part on a response-based strategy
      mediated by the striatum. Both neural strategies eventually relate to equivalent
      performance levels, indicating that covert reorganization of brain patterns
      underlying navigation after sleep is not necessarily accompanied by overt changes
      in behavior.

PMID- 16636289
TI  - Fungi and animals may share a common ancestor to nuclear receptors.
AB  - Nuclear receptors (NRs) are a large family of transcription factors. One hallmark
      of this family is the ligand-binding domain (LBD), for its primary sequence,
      structure, and regulatory function. To date, NRs have been found exclusively in
      animals and sponges, which has led to the generally accepted notion that they
      arose with them. We have overcome the limitations of primary sequence searches by
      combining sequence profile searches with structural predictions at a genomic
      scale, and have discovered that the heterodimeric transcription factors Oaf1/Pip2
      of the budding yeast Saccharomyces cerevisiae contain putative LBDs resembling
      those of animal NRs. Although the Oaf1/Pip2 LBDs are embedded in an entirely
      different architecture, the regulation and function of these transcription
      factors are strikingly similar to those of the mammalian NR heterodimer
      peroxisome proliferator-activated receptor alpha/retinoid X receptor (PPAR
      alpha/RXR). We demonstrate that the induction of Oaf1/Pip2 activity by the fatty
      acid oleate depends on oleate's direct binding to the Oaf1 LBD. The alteration of
      two amino acids in the predicted ligand-binding pocket of Oaf1 abolishes both
      ligand binding and the transcriptional response. Hence, LBDs may have arisen as
      allosteric switches, for example, to respond to nutritional and metabolic
      ligands, before the animal and fungal lineages diverged.

PMID- 16636290
TI  - Targeting AMAP1 and cortactin binding bearing an atypical src homology 3/proline
      interface for prevention of breast cancer invasion and metastasis.
AB  - Invasive potentials of carcinomas greatly contribute to their metastasis, which
      is a major threat in most cancers. We have recently shown that Arf6 plays a
      pivotal role in breast cancer invasive activities and identified AMAP1 as an
      effector of GTP-Arf6 in invasion. Expression of AMAP1 correlates well with
      invasive phenotypes of primary tumors of the human breast. We also have shown
      that AMAP1 functions by forming a trimeric protein complex with cortactin and
      paxillin. In this complex, AMAP1 binds to the src homology 3 (SH3) domain of
      cortactin via its proline-rich peptide, SKKRPPPPPPGHKRT. SH3 domains are known to
      bind generally to the proline-rich ligands with a one-to-one stoichiometry. We
      found that AMAP1/cortactin binding is very atypical in its stoichiometry and
      interface structure, in which one AMAP1 proline-rich peptide binds to two
      cortactin SH3 domains simultaneously. We made a cell-permeable peptide derived
      from the AMAP1 peptide, and we show that this peptide specifically blocks
      AMAP1/cortactin binding, but not other canonical SH3/proline bindings, and
      effectively inhibits breast cancer invasion and metastasis. Moreover, this
      peptide was found to block invasion of other types of cancers, such as
      glioblastomas and lung carcinomas. We also found that a small-molecule compound,
      UCS15A, which was previously judged as a weak inhibitor against canonical
      SH3/proline bindings, effectively inhibits AMAP1/cortactin binding and breast
      cancer invasion and metastasis. Together with fine structural analysis, we
      propose that the AMAP1/cortactin complex, which is not detected in normal mammary
      epithelial cells, is an excellent drug target for cancer therapeutics.

PMID- 16636292
TI  - Acute suppression, but not chronic genetic deficiency, of c-fos gene expression
      impairs long-term memory in aversive taste learning.
AB  - Several lines of evidence have indicated that the establishment of long-term
      memory requires protein synthesis, including the synthesis of immediate-early
      gene products. Although the anatomical expression patterns of the c-fos gene, a
      transcription factor-encoding immediate-early gene, in conditioned taste aversion
      (CTA) are well documented, the functional roles of c-fos gene expression and Fos
      mediated transcription remain to be clarified. Using the antisense
      oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout
      techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene
      expression in the acquisition, retrieval, and retention of CTA. Preconditioning
      microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the
      parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control
      ODNs consisting of a randomized or inverted base order had no effect.
      Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not
      impair the acquisition, whereas it attenuated the retention. Retrieval and
      subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN
      infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed
      against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not
      affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice
      caused normal acquisition and retention. The present results suggest that the Fos
      mediated gene transcription in the PBN, amygdala, or insular cortex plays
      critical roles in the acquisition and/or consolidation, but not the retrieval, of
      long-term taste memory; nevertheless, some other factors could compensate CTA
      mechanism when Fos-mediated transcription is not available.

PMID- 16636291
TI  - A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult
      neural stem cells.
AB  - In the subventricular zone of the adult mammalian forebrain, neural stem cells
      (NSCs) reside and proliferate to generate young neurons. We screened factors that
      promoted the proliferation of NSCs in vitro by a recently developed proteomics
      technique, the ProteinChip system. In this screen, we identified a soluble
      carbohydrate-binding protein, Galectin-1, as a candidate. We show herein that
      Galectin-1 is expressed in a subset of slowly dividing subventricular zone
      astrocytes, which includes the NSCs. Based on results from intraventricular
      infusion experiments and phenotypic analyses of knockout mice, we demonstrate
      that Galectin-1 is an endogenous factor that promotes the proliferation of NSCs
      in the adult brain.

PMID- 16636293
TI  - A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and
      associated parameters in diet-induced obese mice.
AB  - Neuropeptide Y (NPY) is thought to have a major role in the physiological control
      of energy homeostasis. Among five NPY receptors described, the NPY Y5 receptor
      (Y5R) is a prime candidate to mediate some of the effects of NPY on energy
      homeostasis, although its role in physiologically relevant rodent obesity models
      remains poorly defined. We examined the effect of a potent and highly selective
      Y5R antagonist in rodent obesity and dietary models. The Y5R antagonist
      selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body
      weight gain and adiposity while improving the DIO-associated hyperinsulinemia.
      The compound did not affect the body weight of lean mice fed a regular diet or
      genetically obese leptin receptor-deficient mice or rats, despite similarly high
      brain Y5R receptor occupancy. The Y5R antagonist acts in a mechanism-based
      manner, as the compound did not affect DIO of Y5R-deficient mice. These results
      indicate that Y5R is involved in the regulation and development of DIO and
      suggest utility for Y5R antagonists in the treatment of obesity.

PMID- 16636294
TI  - Short blocks from the noncoding parts of the human genome have instances within
      nearly all known genes and relate to biological processes.
AB  - Using an unsupervised pattern-discovery method, we processed the human intergenic
      and intronic regions and catalogued all variable-length patterns with identically
      conserved copies and multiplicities above what is expected by chance. Among the
      millions of discovered patterns, we found a subset of 127,998 patterns, termed
      pyknons, which have additional nonoverlapping instances in the untranslated and
      protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons
      arrange combinatorially in the untranslated and coding regions of numerous human
      genes where they form mosaics. Consecutive instances of pyknons in these regions
      show a strong bias in their relative placement, favoring distances of
      approximately 22 nucleotides. We also found pyknons to be enriched in a
      statistically significant manner in genes involved in specific processes, e.g.,
      cell communication, transcription, regulation of transcription, signaling,
      transport, etc. For approximately 1/3 of the pyknons, the intergenic/intronic
      instances of their reverse complement lie within 380,084 nonoverlapping regions,
      typically 60-80 nucleotides long, which are predicted to form double-stranded,
      energetically stable, hairpin-shaped RNA secondary structures; additionally, the
      pyknons subsume approximately 40% of the known microRNA sequences, thus
      suggesting a possible link with posttranscriptional gene silencing and RNA
      interference. Cross-genome comparisons reveal that many of the pyknons have
      instances in the 3' UTRs of genes from other vertebrates and invertebrates where
      they are overrepresented in similar biological processes, as in the human genome.
      These unexpected findings suggest potential unique functional connections between
      the coding and noncoding parts of the human genome.

PMID- 16636296
TI  - Another crack in the edifice of the brain-blood interface.

PMID- 16636295
TI  - Prevention of diabetes by inhibition of tyrosine phosphatases.

PMID- 16636297
TI  - Choline transport for phospholipid synthesis.
AB  - Choline is an essential nutrient for all cells because it plays a role in the
      synthesis of the membrane phospholipid components of the cell membranes, as a
      methyl-group donor in methionine metabolism as well as in the synthesis of the
      neurotransmitter acetylcholine. Choline deficiency affects the expression of
      genes involved in cell proliferation, differentiation, and apoptosis, and it has
      been associated with liver dysfunction and cancer. Abnormal choline transport and
      metabolism have been implicated in a number of neurodegenerative disorders such
      as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport
      and the characteristics of choline transporters are of central importance to
      understanding the mechanisms that underlie membrane integrity and cell signaling
      in such disorders. Kinetic studies with radiolabeled choline and inhibitors
      distinguish three systems for choline transport: (i) low-affinity facilitated
      diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate
      affinity, Na+-independent transport. It is only recently, however, that the
      proteins having transport characteristics of at least one of these systems have
      been identified. They include (i) polyspecific organic cation transporters (OCTs)
      with low affinity for choline, (ii) high-affinity choline transporters (CHT1s),
      and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1
      and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3
      and essentially display characteristics of specialized transporters for targeted
      choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies
      choline for acetyl-choline synthesis. The focus here is more on newly-discovered
      CTL1 choline transporters. They are expressed in different organisms and cell
      types, apparently not for the biosynthesis of acetylcholine but for the
      production of the most abundant metabolite of choline, the membrane lipid
      phosphatidylcholine.

PMID- 16636298
TI  - Molecular mechanisms of prothrombotic risk due to genetic variations in platelet
      genes: Enhanced outside-in signaling through the Pro33 variant of integrin beta3.
AB  - In recent years inherited variations in platelet proteins have emerged as
      potential risk factors that could predispose individuals to arterial thrombosis.
      Although many studies have examined the association of platelet gene
      polymorphisms with particular disease states, the underlying mechanisms by which
      most of these polymorphisms contribute to the pathophysiology of thrombosis have
      remained largely unexplored. This review will focus on the cellular and molecular
      features by which these genetic changes affect platelet physiology. Although many
      genes have been investigated in this regard, only the genes encoding integrins
      beta3 and alpha2, and the platelet Fc receptor, Fc(gamma)RIIA, have been studied
      in any depth. In some cases (such as integrin alpha2), evidence supports a
      quantitative trait locus. For other genes, nonsynonymous nucleotide substitutions
      lead to structural and functional consequences. A large portion of this review
      will focus on the widely studied Leu33Pro (Pl(A)) polymorphism of integrin beta3,
      and will consider the potential mechanisms by which the Pro33 polymorphism could
      induce a prothrombotic risk. A detailed understanding of how polymorphisms
      modulate platelet physiology will be important for understanding individual
      differences in response to antiplatelet therapy.

PMID- 16636299
TI  - Novel mechanisms for estrogen-induced neuroprotection.
AB  - Estrogens are gonadal steroid hormones that are present in the circulation of
      both males and females and that can no longer be considered within the strict
      confines of reproductive function. In fact, the bone, the cardiovascular system,
      and extrahypothalamic regions of the brain are now well-established targets of
      estrogens. Among the numerous aspects of brain function regulated by estrogens
      are their effects on mood, cognitive function, and neuronal viability. Here, we
      review the supporting evidence for estrogens as neuroprotective agents and
      summarize the various mechanisms that may be involved in this effect, focusing
      particularly on the mitochondria as an important target. On the basis of this
      evidence, we discuss the clinical applicability of estrogens in treating various
      age-related disorders, including Alzheimer disease and stroke, and identify the
      caveats that must be considered.

PMID- 16636300
TI  - Alterations of Fas and Fas-related molecules in patients with silicosis.
AB  - Persons with silicosis have not only respiratory disorders but also autoimmune
      diseases. To clarify the mechanisms involved in the dysregulation of autoimmunity
      found in patients with silicosis, we have been focusing on Fas and Fas-related
      molecules in the Fas-mediated apoptotic pathway, because Fas is one of the most
      important molecules regulating auto-immunity involving T cells. Our findings
      showed that patients with silicosis exhibited elevated serum soluble Fas levels,
      an increased relative expression of the soluble fas and dcr3 genes in peripheral
      blood mononuclear cells, high levels of other variant messages of the fas
      transcript, relatively decreased expression of genes encoding several
      physiological inhibitors (such as survivin and toso), and dominancy of lower
      membrane Fas expressers in lymphocytes, which transcribe soluble fas dominantly,
      compared with soluble fas transcription in healthy donors. These findings are
      consistent with known features regarding immunological factors, such as serum
      immunogulobulin G levels and the titer of anti-nuclear autoantibodies in
      silicosis. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody
      were detected in serum specimens from patients with silicosis, and a functional
      assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. We
      hypothesize that there are two subpopulations of silicosis lymphocytes. One is a
      long-term surviving fraction that includes self-recognizing clones showing lower
      levels of membrane Fas and inhibition of Fas/Fas ligand binding in extracellular
      spaces. The other subpopulation exhibits apoptosis caused by silica and
      silicates, is recruited from bone marrow, shows higher levels of membrane Fas,
      and is sensitive to anti-Fas autoantibody. Further investigation should be
      performed to confirm the effects of silica and silicates on the human immune
      system.

PMID- 16636301
TI  - Activin signaling and its role in regulation of cell proliferation, apoptosis,
      and carcinogenesis.
AB  - Activins, cytokine members of the transforming growth factor-beta superfamily,
      have various effects on many physiological processes, including cell
      proliferation, cell death, metabolism, homeostasis, differentiation, immune
      responses endocrine function, etc. Activins interact with two structurally
      related serine/threonine kinase receptors, type I and type II, and initiate
      downstream signaling via Smads to regulate gene expression. Understanding how
      activin signaling is controlled extracellularly and intracellularly would not
      only lead to more complete understanding of cell growth and apoptosis, but would
      also provide the basis for therapeutic strategies to treat cancer and other
      related diseases. This review focuses on the recent progress on activin-receptor
      interactions, regulations of activin signaling by ligand-binding proteins,
      receptor-binding proteins, and nucleocytoplasmic shuttling of Smad proteins.

PMID- 16636302
TI  - Double null of selenium-glutathione peroxidase-1 and copper, zinc-superoxide
      dismutase enhances resistance of mouse primary hepatocytes to acetaminophen
      toxicity.
AB  - This study was conducted to determine the impact of knockout of selenium (Se)
      dependent glutathione peroxidase-1 (GPX1-/-) or double knockout of GPX1 and
      copper, zinc (Cu,Zn)-super-oxide dismutase (SOD1) on cell death induced by
      acetaminophen (APAP) and its major toxic metabolite N-acetyl-P-benzoquinoneimine
      (NAPQI). Primary hepatocytes were isolated from GPX1-/-, double knockout of GPX1
      and SOD1 (DKO), and their wild-type (WT) mice and were treated with 5 mM APAP or
      100 microM NAPQI for 0, 6, and 12 hrs. Compared with the WT cells, the GPX1-/-
      and DKO hepatocytes were more resistant (P < 0.05) to the APAP-induced cell death
      but less resistant to the NAPQI-induced cell death. The APAP-mediated glutathione
      (GSH) depletion was greater (P < 0.05) at 6 hrs in the WT cells than in the GPX1
      /- and DKO cells, whereas there was no genotype effect on the NAPQI-mediated GSH
      depletion. The DKO cells had lower (P < 0.05) microsomal cytochrome P450 2E1
      activities, but higher (P < 0.05) glutathione reductase and thioredoxin reductase
      activities than the WT cells at 0 hrs, and they responded differently to the APAP
      and NAPQI treatments. Glutathione-S-transferase activity was not affected by
      genotypes or treatments. Neither APAP nor NAPQI induced nitric oxide production
      or protein nitration in cells of any genotype. However, the GPX1-/- and DKO cells
      were more resistant to peroxynitrite-mediated protein nitration than were the WT
      cells. In conclusion, double null of GPX1 and SOD1 enhanced the resistance of
      mouse primary hepatocytes to APAP toxicity by affecting events prior to or at
      NAPQI formation. While the double knockout attenuated the peroxynitrite-mediated
      protein nitration in hepatocytes, no protein nitration was detected in these
      cells treated with APAP or NAPQI.

PMID- 16636303
TI  - Marginal zinc deficiency increased the susceptibility to acute lipopolysaccharide
      induced liver injury in rats.
AB  - Lipopolysaccharide (LPS) triggers a global activation of inflammatory responses
      leading to liver injury in humans. Zinc pretreatment has been shown to prevent
      LPS-induced hepatic necrosis. In North America, suboptimal zinc status is more
      common than once realized. However, the effect of inadequate zinc nutrition on
      the host's susceptibility to LPS-induced liver injury is not known. The objective
      of this study was to determine whether marginal zinc deficiency would render rats
      more susceptible to LPS-induced liver injury. Weanling Sprague-Dawley rats were
      assigned to one of three dietary treatment groups: marginally low zinc ad libitum
      (Z3; 3 mg zinc/kg diet), adequate zinc ad libitum (Z30; 30 mg zinc/kg diet), or
      adequate zinc pair-fed (Z30P) group. After 6 weeks, each dietary treatment group
      was further divided into LPS-control (saline) groups (C-Z3, C-Z30P, C-Z30) and
      LPS-treatment (1 mg/kg body weight, intraperitoneal, 8 hrs) groups (LPS-Z3, LPS
      Z30P, LPS-Z30). LPS reduced the serum zinc concentration and increased the liver
      zinc concentration regardless of dietary zinc intake. Serum alanine
      aminotransferase level was higher in the LPS-Z3 rats than in the LPS-Z30P and LPS
      Z30 rats. LPS also induced hepatocyte necrosis and neutrophil infiltration into
      the liver sinusoids. This LPS-induced liver damage was more severe in the LPS-Z3
      rats than in the LPS-Z30P and LPS-Z30 rats. Together these findings have
      demonstrated that marginal zinc deficiency increased the susceptibility to LPS
      induced liver injury in rats. These results indicate that patients with sepsis
      who have suboptimal zinc nutrition status may be at higher risk of developing
      greater liver damage.

PMID- 16636304
TI  - Selective compensatory induction of hepatic HMG-CoA reductase in response to
      inhibition of cholesterol absorption.
AB  - The effect of the potent inhibitor of cholesterol absorption, ezetimibe, on serum
      cholesterol levels was tested in diabetic and thyroidectomized male Sprague
      Dawley rats. Feeding diets supplemented with 1% cholesterol to the diabetic rats
      raised serum cholesterol levels from 132 to 514 mg/dl while decreasing hepatic 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase protein and mRNA levels.
      Addition of 10 mg/kg/day of ezetimibe to the diets of these animals lowered the
      serum cholesterol level to 90 mg/dl and produced a large compensatory increase in
      hepatic HMG-CoA reductase protein without significantly increasing mRNA levels,
      indicating a post-transcriptional effect. Hepatic LDL receptor protein levels in
      these diabetic rats were unaffected by ezetimibe treatment. In contrast,
      ezetimibe treatment of these young normal Sprague-Dawley rats, known to express
      high levels of hepatic HMG-CoA reductase, did not lower serum cholesterol levels.
      In thyroidectomized rats, dietary cholesterol increased serum cholesterol levels
      from 116 to 135 mg/dl and ezetimibe treatment lowered these elevated cholesterol
      levels to 85 mg/dl. Cholesterol feeding of thyroidectomized rats severely reduced
      hepatic HMG-CoA reductase protein, while ezetimibe treatment restored reductase
      protein to normal levels. Again, hepatic LDL receptor protein levels were
      unaffected by ezetimibe treatment of cholesterol-fed thyroidectomized rats. The
      data demonstrate that the cholesterol absorption inhibitor ezetimibe profoundly
      lowers serum cholesterol levels in animals expressing very low rates of hepatic
      cholesterol synthesis and produces large compensatory increases in hepatic HMG
      CoA reductase expression without significantly affecting expression of hepatic
      LDL receptors. This indicates that ezetimibe should be most effective in lowering
      serum cholesterol levels in people with low rates of cholesterol synthesis/high
      rates of cholesterol absorption.

PMID- 16636305
TI  - Developmental changes in ovine myocardial glucose transporters and insulin
      signaling following hyperthermia-induced intrauterine fetal growth restriction.
AB  - Developmental changes in ovine myocardial glucose transporters and insulin
      signaling following hyperthermia-induced intrauterine fetal growth restriction
      (IUGR) were the focus of our study. Our objective was to test the hypothesis that
      the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose
      transporter protein expression, plasma membrane-bound glucose transporter protein
      concentrations, and insulin signal transduction protein concentrations. Growth
      measurements and whole heart tissue were obtained at 55 days gestational age
      (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and
      hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial
      blood was obtained and Doppler ultrasound was used to determine umbilical artery
      systolic (S) and diastolic (D) flow velocity waveform profiles to calculate
      pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1,
      Glut-4, insulin signal transduction proteins involved in Glut-4 translocation,
      and glycogen content were measured. Compared to age-matched controls, HT 90-dGA
      fetal body weights and HT 135-dGA fetal weights and gross heart weights were
      lower. Heart weights as a percent of body weights were similar between C and HT
      sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose
      and insulin concentrations, (ii) lower arterial blood oxygen content and higher
      plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane
      (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv)
      higher myocardial glycogen content, and (v) higher umbilical artery Doppler
      pulsatility and resistance indices. The HT ovine fetal myocardium adapts to
      reduced circulating glucose and insulin concentrations by increasing plasma
      membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut
      4 PM and IRbeta protein concentrations likely contribute to or increase the
      intracellular delivery of glucose and, together with the increased lactate
      concentrations, enhance glycogen synthesis, which allows for maintained
      myocardial growth commensurate with fetal body growth.

PMID- 16636306
TI  - Effect of nitric oxide synthase inhibition on proteinuria in glomerular immune
      injury.
AB  - In glomerular immune injury, the inducible isoform of nitric oxide synthase
      (iNOS) becomes a major catalyst of NO production. Although iNOS-catalyzed NO
      production is sustained and can be cytotoxic, iNOS inhibition exacerbates the
      magnitude of proteinuria that accompanies immune injury. To investigate putative
      mechanisms of this effect, we assessed changes in glomerular permeability to
      albumin by using the following two approaches: (i) an in vivo rat model of
      glomerular immune injury induced by antibody against the glomerular basement
      membrane (GBM), in which urine albumin excretion was measured under conditions of
      iNOS inhibition, and (ii) an ex vivo model of isolated rat glomeruli, in which
      changes in glomerular capillary permeability to albumin were assessed under
      conditions of NOS inhibition. In rats with anti-GBM antibody-induced glomerular
      injury, there was an increase in urine albumin excretion. Treatment with two
      structurally dissimilar iNOS inhibitors at doses sufficient to decrease urine
      nitrate and/or nitrite exacerbated proteinuria. In these animals, urine excretion
      of the isoprostane 8-iso-PGF2alpha (marker of oxidative stress) was increased. In
      isolated glomeruli incubated with the NOS inhibitor L-NMMA, the permeability to
      albumin increased. This effect was reversed by the NO donor DETA NONOate and by
      the superoxide dismutase mimetic Tempol. We conclude that NOS-catalyzed NO
      production is an important mechanism in regulating glomerular permeability to
      protein. This mechanism involves control of the bioavailability of superoxide.

PMID- 16636307
TI  - Diversities of podocyte molecular changes induced by different antiproteinuria
      drugs.
AB  - Nephrin, podocin, CD2AP, and alpha-actinin-4 are important podocyte proteins that
      help maintain the integrity of the slit diaphragm and prevent proteinuria.
      Studies have shown that angiotensin-converting enzyme inhibitors,
      glucocorticoids, and all-trans retinoic acid (ATRA) have antiproteinuric effects.
      However, it is still unclear whether these drugs, with different pharmacological
      mechanisms, lead to a reduction in proteinuria by changing the expression and
      distribution of these important podocyte proteins. In this study, changes in the
      expression and distribution of nephrin, podocin, CD2AP, and alpha-actinin-4 were
      dynamically detected in Adriamycin-induced nephrotic (ADR) rats treated with
      three different drugs: lisinopril, prednisone, and ATRA. Nephropathy was induced
      by an intravenous injection of Adriamycin. After Adriamycin injection, rats
      received lisinopril, prednisone, and ATRA treatment, respectively. Renal tissues
      were collected at Days 3, 7, 14, and 28. The distribution and the expression of
      messenger RNA and protein of nephrin, podocin, CD2AP, and alpha-actinin-4 were
      detected by indirect immunofluorescence, real-time polymerase chain reaction, and
      Western blotting, respectively. With the intervention of lisinopril, prednisone,
      and ATRA, changes in the expression of nephrin, podocin, and CD2AP were diverse,
      which was different from that detected in ADR rats. After lisinopril and
      prednisone intervention, podocin exhibited prominent earlier changes compared
      with those of nephrin and CD2AP, whereas CD2AP showed more prominent changes
      after ATRA intervention. There was no change in the expression of alpha-actinin-4
      molecule. In summary, we conclude that the antiproteinuric effects of lisinopril,
      prednisone, and ATRA were achieved by changes in the expression and distribution
      of the important podocyte molecules nephrin, podocin, CD2AP, and alpha-actinin-4.
      The pattern in the change of podocyte molecules after lisinopril and prednisone
      intervention was similar, but the pattern in the change of podocyte molecules
      after ATRA intervention was different from that of lisinopril or prednisone
      intervention.

PMID- 16636308
TI  - Effect of apple extracts on NF-kappaB activation in human umbilical vein
      endothelial cells.
AB  - The mechanisms by which foods, such as fruit, are able to reduce the risk of
      chronic disease are still unclear. Several fruit products, including apples and
      apple juice, that are flavonoid-rich are reported to increase antioxidant levels
      in human subjects. This is supported by the finding from our previous studies
      that the chronic consumption of apple juice by human subjects reduced ex vivo low
      density lipoprotein (LDL) oxidation; we hypothesized that this was due to the
      flavonoid in the apple juice, which, as we reported earlier, reduced in vitro LDL
      oxidation. To further explore whether the mixture of flavonoids and other
      phytochemicals in apples are biologically relevant antioxidants, we tested the
      effects of this flavonoid-rich apple extract (AE) on oxidant-related pathways in
      a model of the endothelium: human umbilical vascular endothelial cells (HU-VECs).
      The effects of AE on oxidant-responsive (i.e., tumor necrosis factor [TNF]-alpha
      induced) nuclear factor (NF)- kappaB signaling in cell culture were assessed in
      transfected HUVECs by using a construct that expressed luciferase under the
      control of NF-kappaB. Incubation of HUVEC for 24 hrs with up to 10 mM (as gallic
      acid equivalents) of AE demonstrated no cytotoxicity, as determined by lactate
      dehydrogenase release, caspase 3 activation, and apoptosis marker-based FACS
      analysis. AE after a 24-hr incubation period at either 200 or 2000 nM showed a
      complex pattern of decreased basal and TNF-alpha-stimulated NF-kappaB signaling
      (63% maximal decrease) as assessed by luciferase activity in the transfected
      HUVECs, as well as by reduced levels of IkappaBalpha protein phosphorylation
      detected by Western blot analysis. We suggest that AE downregulates NF-kappaB
      signaling and that this is indicative of an antioxidant effect of the flavonoids
      present in AE.

PMID- 16636309
TI  - Expression of cytosolic NADP+-dependent isocitrate dehydrogenase in bovine
      mammary epithelium: Modulation by regulators of differentiation and metabolic
      effectors.
AB  - The cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) catalyzes the
      conversion of isocitrate to alpha-ketoglutarate in the cytosol, and generates
      NADPH as a primary source of reducing equivalents for de novo fatty acid
      synthesis in bovine mammary gland. The enzymatic activity of IDH1 increases
      dramatically in early lactation in bovine mammary tissue. We hypothesized that
      the expression of IDH1 in bovine is modulated by regulators of mammary epithelial
      differentiation. To test this hypothesis, we first examined the changes in IDH1
      expression in late pregnancy (-20 days) and at various stages (14, 90, 120, and
      240 days) of lactation in bovine mammary tissue. IDH1 mRNA levels increased by
      2.3-fold after parturition compared to late pregnancy and remained elevated
      thereafter. Next, we examined the effects of extracellular matrix and lactogenic
      hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial
      cells. We found that expression of IDH1 mRNA increased in parallel with beta
      casein expression induced by extracellular matrix. Fetal calf serum and insulin
      repressed, whereas prolactin stimulated the expression of IDH1 mRNA in a dose
      dependent fashion. The inhibitory effects of insulin on IDH1 mRNA levels were
      antagonized by cotreatment with prolactin. In contrast, treatment with prolactin
      in the presence of extracellular matrix further increased IDH1 mRNA and protein
      accumulation. Prolactin-induced IDH1 expression was inhibited by the mitogen
      activated protein kinase (MAPK) inhibitors PD98059 and U0126, and Janus tyrosine
      kinase 2 (Jak2) inhibitor AG490, suggesting that both MAPK and Jak2 contribute to
      regulation of IDH1 expression by prolactin. Finally, we report that treatment of
      BME-UV cells with alpha-ketoglutarate and palmitic acid reduced IDH1 transcript
      levels. Taken together, our data suggest that the expression of IDH1 in bovine
      mammary epithelium is modulated by regulators of differentiation including
      extracellular matrix and lactogenic hormones as well as metabolic effectors.

PMID- 16636310
TI  - Nuclear accumulations of p53 and Mdm2 are accompanied by reductions in c-Abl and
      p300 in zinc-depleted human hepatoblastoma cells.
AB  - The influence of zinc status on the expression of proteins known to be involved
      in the stability of p53, the human tumor suppressor gene product, was examined in
      hepatoblastoma (HepG2) cells. Cells were cultured in zinc-deficient (ZD0.2,
      ZD0.4), zinc normal (ZN), zinc adequate (ZA), or zinc-supplemented (ZS) medium,
      which contained 0.2, 0.4, 4, 16, or 32 microM zinc, respectively. Nuclear p53
      levels were almost 100% and 40% higher in ZD0.2 and ZD0.4 cells, respectively,
      than in ZN cells. Mdm2 protein, which mediates p53 degradation, was 174% and 148%
      higher in the nucleus of ZD0.2 and ZD0.4 cells, respectively, than in ZN cells.
      In addition, the observed reductions of nuclear c-Abl in ZD0.2 and ZD0.4 cells to
      50% and 60% of ZN cells, respectively, may be a cellular response attempting to
      normalize nuclear p53 accumulation because nuclear c-Abl is known to down
      regulate ubiquitination and nuclear export of p53. Moreover, no changes in total
      cellular p53, Mdm2, and c-Abl or nuclear Mdmx were observed among the treatment
      groups. Furthermore, in ZD0.2 and ZD0.4 cells, the reduction in total and nuclear
      p300, which is known to complex with CREB-binding protein and Mdm2 in the nucleus
      for the generation of degradable polyubiquitinated form of p53, may have
      depressed the degradation pathway for p53 and Mdm2, and contributed to the
      nuclear accumulation of these proteins in ZD cells.

PMID- 16636311
TI  - Retinoic acid exerts dual regulatory actions on the expression and nuclear
      localization of interferon regulatory factor-1.
AB  - Interferon regulatory factor-1 (IRF-1), a transcription factor and tumor
      suppressor involved in cell growth regulation and immune responses, has been
      shown to be induced by all-trans retinoic acid (ATRA). However, the factors
      controlling the cellular location and activity of IRF-1 are not well understood.
      In this study, we examined the expression of IRF-1 and its nuclear localization,
      DNA-binding activity, and target gene expression in human mammary epithelial
      MCF10A cells, a model of breast epithelial cell differentiation and
      carcinogenesis. Following initial treatment with ATRA, IRF-1 mRNA and protein
      were induced within 2 hrs, reached a peak (>30-fold induction) at 8 hrs, and
      declined afterwards. IRF-1 protein was predominantly cytoplasmic during this
      treatment. Although a second dose of ATRA or Am580 (a related retinoid selective
      for retinoic acid receptor-alpha [RARalpha]), given 16 hrs after the first dose,
      restimulated IRF-1 mRNA and protein levels to a similar level to that obtained by
      the first dose, IRF-1 was predominantly concentrated in the nucleus after
      restimulation. ATRA and Am580 also increased nuclear RARalpha, whereas retinoid X
      receptor-alpha (RXRalpha)--a dimerization partner for RARalpha, was localized to
      the nucleus upon second exposure to ATRA. However, ATRA and Am580 did not
      regulate the expression or activation of signal transducer and activator of
      transcription-1 (STAT-1), a transcription factor capable of inducing the
      expression of IRF-1, indicating an STAT-1-independent mechanism of regulation by
      ATRA and Am580. The increase in nuclear IRF-1 after retinoid restimulation was
      accompanied by enhanced binding to an IRF-E DNA response element, and elevated
      expression of an IRF-1 target gene, 2',5'-oligoadenylate synthetase-2. The dual
      effect of retinoids in increasing IRF-1 mRNA and protein and in augmenting the
      nuclear localization of IRF-1 protein may be essential for maximizing the tumor
      suppressor activity and the immunosurveillance functions of IRF-1 in breast
      epithelial cells.

PMID- 16636312
TI  - Global gene expression in mouse vaginae exposed to diethylstilbestrol at
      different ages.
AB  - Estrogens regulate proliferation and differentiation of cells in target organs
      such as the female reproductive tract. In mature mice, estrogens stimulate cell
      proliferation, whereas ovariectomy results in atrophy of the female reproductive
      tract. In contrast, perinatal exposure to estrogens, including diethylstilbestrol
      (DES), induces persistent, ovary-independent vaginal stratification and cervico
      vaginal tumors later in life. These effects are due to altered cell fate
      following DES exposure during a critical developmental period. The detailed
      mechanisms underlying the reversible and irreversible cell proliferation in
      vaginae induced by DES at different ages has not been clarified. Therefore, we
      examined differences in gene expression pattern using DNA microarray analysis in
      mouse vaginae 6 hrs after a single injection of 2 mug DES per gram of body
      weight, and proliferation of vaginal epithelial and stromal cells 24 hrs after
      the injection at postnatal days (PNDs) 0, 5, 20, and 70. After DES stimulation,
      vaginal epithelial and stromal cells showed cell proliferation at PNDs 20 and 70,
      and at PNDs 0 and 5, respectively. DNA microarray analysis exhibited 54 DES
      induced genes and 9 DES-repressed genes in vaginae at PND 0, whereas more than
      200 DES-induced genes were found in vaginae at PNDs 5 and 20, and 350 genes at
      PND 70. Clustering analysis of DES-induced genes in the vaginae at different ages
      revealed that genes induced by DES at PND 5 were closer to the adult type than
      that of PND 0. Genes related to keratinocyte differentiation, such as
      Gadd45alpha, p21, 14-3-3 sigma, small proline-rich protein 2f (Sprr2f), and
      Krupple-like factor 4 (Klf4), were induced by DES. The number of DES-induced
      genes during the critical period, PND 0, was smaller than those found after the
      critical period. These results give insight toward understanding the molecular
      mechanisms underlying the critical period in mouse vaginae.

PMID- 16636313
TI  - Cyanide detoxification by the cobalamin precursor cobinamide.
AB  - Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase,
      thereby depleting cellular ATP. It contributes to smoke inhalation deaths in
      fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12)
      binds cyanide with a relatively high affinity and is used in Europe to treat
      smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin
      biosynthesis, binds cyanide with about 10(10) greater affinity than cobalamin,
      and we found it was several-fold more effective than cobalamin in (i) reversing
      cyanide inhibition of oxidative phosphorylation in mammalian cells; (ii) rescuing
      mammalian cells and Drosophila melanogaster from cyanide toxicity; and (iii)
      reducing cyanide inhibition of Drosophila Malpighian tubule secretion. Cobinamide
      could be delivered by oral ingestion, inhalation, or injection to Drosophila, and
      it was as effective when administered up to 5 mins post-cyanide exposure as when
      given pre-exposure. We conclude that cobinamide is an effective cyanide
      detoxifying agent that has potential use as a cyanide antidote, both in smoke
      inhalation victims and in persons exposed to cyanide used as a weapon of mass
      destruction.

PMID- 16636314
TI  - The quest to improve Aboriginal health.

PMID- 16636316
TI  - Conscription fears accompany threat of pandemic.

PMID- 16636317
TI  - Apples, oranges and wait times: CIHI report.

PMID- 16636318
TI  - Wait-list weary Canadians seek treatment abroad.

PMID- 16636319
TI  - Safe drinking water standards for First Nations communities.

PMID- 16636321
TI  - Providing health care to medically uninsured immigrants and refugees.

PMID- 16636322
TI  - Safe medication prescribing and monitoring in the outpatient setting.

PMID- 16636323
TI  - Measles, again--and its implications for occupational health.

PMID- 16636324
TI  - A rare cause of upper gastrointestinal bleeding.

PMID- 16636325
TI  - Is watchful waiting a reasonable approach for men with minimally symptomatic
      inguinal hernia?

PMID- 16636326
TI  - Association of low intake of milk and vitamin D during pregnancy with decreased
      birth weight.
AB  - BACKGROUND: Some pregnant women may be advised or choose to restrict milk
      consumption and may not take appropriate supplements. We hypothesized that
      maternal milk restriction during pregnancy, which can reduce intakes of protein,
      calcium, riboflavin and vitamin D, might represent a health risk by lowering
      infant birth weight. METHODS: We screened women between the ages of 19 and 45
      years who were attending prenatal programs in Calgary, Alberta (51 degrees N) for
      low milk consumption (< or = 250 mL/d). Using repeat dietary recalls, we compared
      these women and their offspring with women whose daily milk consumption exceeded
      250 mL (1 cup). Birth weight, length and head circumference were obtained from
      birth records. RESULTS: Women who consumed < or = 250 mL/d of milk (n = 72) gave
      birth to infants who weighed less than those born to women who consumed more (n =
      207; 3410 g v. 3530 g, respectively; p = 0.07). Infant lengths and head
      circumferences were similar. Women who restricted milk intake had statistically
      significantly lower intakes of protein and vitamin D as well. In multivariate
      analyses controlled for previously established predictors of infant birth weight,
      milk consumption and vitamin D intake were both significant predictors of birth
      weight. Each additional cup of milk daily was associated with a 41 g increase in
      birth weight (95% confidence interval [CI] 14.0-75.1 g); each additional
      microgram of vitamin D, with an 11 g increase (95% CI 1.2-20.7 g). Neither
      protein, riboflavin nor calcium intake was found to predict birth weight.
      INTERPRETATION: Milk and vitamin D intakes during pregnancy are each associated
      with infant birth weight, independently of other risk factors.

PMID- 16636327
TI  - Warfarin interaction with Matricaria chamomilla.
AB  - No cases have been reported of Matricaria chamomilla potentiating the effects of
      warfarin. Nevertheless there is a theoretical risk for potentiation, since the
      herb is thought to be a coumarin constituent. We describe the case of a 70-year
      old woman who, while being treated with warfarin, was admitted to hospital with
      multiple internal hemorrhages after having used chamomile products (tea and body
      lotion) to soothe upper respiratory tract symptoms. Patient education on the
      potential risk of taking chamomile products while being treated with warfarin is
      necessary to avoid such occurrences.

PMID- 16636328
TI  - Overcoming clinical inertia in the management of hypertension.

PMID- 16636329
TI  - Nutritional vitamin D status during pregnancy: reasons for concern.

PMID- 16636330
TI  - The effect of obesity on chronic respiratory diseases: pathophysiology and
      therapeutic strategies.
AB  - Sedentary lifestyles and increased pollution brought about by industrialization
      pose major challenges to the prevention of both obesity and chronic respiratory
      diseases such as chronic obstructive pulmonary disease (COPD), asthma,
      obstructive sleep apnea and obesity hypoventilation syndrome. Obesity has emerged
      as an important risk factor for these respiratory diseases, and in many instances
      weight loss is associated with important symptomatic improvement. Moreover,
      obesity may influence the development and presentation of these diseases. In this
      article, we review the current understanding of the influence of obesity on
      chronic respiratory diseases and the clinical management of obesity concurrent
      with asthma, COPD, obstructive sleep apnea or obesity hypoventilation syndrome.

PMID- 16636331
TI  - Questions about Adderall XR.

PMID- 16636332
TI  - Use of OxyContin by adolescent students.

PMID- 16636335
TI  - Ten-year multi-institutional results of breast-conserving surgery and
      radiotherapy in BRCA1/2-associated stage I/II breast cancer.
AB  - PURPOSE: We compared the outcome of breast-conserving surgery and radiotherapy in
      BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic
      controls. METHODS: A total of 160 BRCA1/2 mutation carriers with breast cancer
      were matched with 445 controls with sporadic breast cancer. Primary end points
      were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers
      (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for
      controls. RESULTS: There was no significant difference in IBTR overall between
      carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers
      and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19).
      Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent
      predictor of IBTR when carriers who had undergone oophorectomy were removed from
      analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone
      oophorectomy was not significantly different from that in sporadic controls (P =
      .37). CBCs were significantly greater in carriers versus controls, with 10- and
      15-year estimates of 26% and 39% for carriers and 3% and 7% for controls,
      respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of
      CBCs in mutation carriers (HR, 0.31; P = .05). CONCLUSION: IBTR risk at 10 years
      is similar in BRCA1/2 carriers treated with breast conservation surgery who
      undergo oophorectomy versus sporadic controls. As expected, CBCs are
      significantly increased in carriers. Although the incidence of CBCs was
      significantly reduced in mutation carriers who received tamoxifen, this rate
      remained significantly greater than in controls. Additional strategies are needed
      to reduce contralateral cancers in these high-risk women.

PMID- 16636336
TI  - Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam
      radiation therapy in patients with locally advanced rectal cancer: Cancer and
      Leukemia Group B 89901.
AB  - PURPOSE: The addition of oxaliplatin to fluorouracil in patients with advanced
      colorectal cancer improves survival. This phase I/II study evaluated the addition
      of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and
      external-beam radiation therapy (RT) in patients with locally advanced rectal
      adenocarcinoma. PATIENTS AND METHODS: Patients with clinical T3/T4 rectal
      adenocarcinoma and no evidence of metastases were treated with weekly
      oxaliplatin, continuous infusion FU 200 mg/m2 intravenously, and RT. A total of 6
      weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total
      dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60
      mg/m2. RESULTS: Forty-four patients were entered onto the study, 18 on the phase
      I portion and 26 on the phase II portion. The maximum-tolerated dose (MTD) for
      oxaliplatin was determined to be 60 mg/m2. At the MTD, 12 patients experienced
      grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one
      patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients
      entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32
      patients enrolled at the phase II dose experienced a pathologic complete
      response. CONCLUSION: In this multicenter study, the addition of oxaliplatin to
      intravenous continuous infusion FU and RT for patients with locally advanced
      rectal cancer was associated with a high pathologic complete response rate but
      more toxicity than when FU is used alone. A regimen of weekly oxaliplatin,
      continuous infusion FU, and radiation therapy is now being evaluated by the
      National Surgical Adjuvant Breast and Bowel Project.

PMID- 16636337
TI  - Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas
      predicts poor prognosis and transformation to diffuse large B-cell lymphoma.
AB  - PURPOSE: Gene expression profiling studies have reported upregulated mRNA
      expression of forkhead box protein P1 (FOXP1) in response to normal B-cell
      activation and high expression in a poor prognosis subtype of diffuse large B
      cell lymphoma (DLBCL). Recently, it was also found that FOXP1 rearrangements and
      expression of its protein occur in mucosa-associated lymphoid tissue (MALT)
      lymphomas. In this study, we investigated FOXP1 expression in its relationship to
      morphology, genetic features, and prognosis in a series of 70 MALT lymphomas.
      PATIENTS AND METHODS: All samples were morphologically reviewed and stained for
      FOXP1. Presence of structural and/or numeric aberrations of the FOXP1, BCL10, and
      MALT1 genes was investigated. For all patients, a complete clinical data set was
      collected. RESULTS: We detected nuclear expression of FOXP1 in 20 of the 70 MALT
      lymphomas (nine of them featuring structural or numeric aberrations of the FOXP1
      locus). FOXP1 positivity was confined to MALT lymphomas with poor clinical
      outcome (with impact of FOXP1 expression on relapse rate and disease-free
      survival). It was also found that MALT lymphomas with strong FOXP1 expression are
      at risk of transforming into an aggressive DLBCL of nongerminal center phenotype
      if they feature, in addition, a polymorphic histology and the presence of trisomy
      3 and 18. CONCLUSION: The data presented show that FOXP1 expression is an
      independent prognostic factor in MALT lymphomas. The data also support the
      hypothesis that a subgroup of nongerminal center DLBCLs (those marked by FOXP1
      expression and trisomy 3 and 18) might represent a large-cell variant of MALT
      lymphomas.

PMID- 16636338
TI  - A "bone" fide predictor of metastasis? Predicting breast cancer metastasis to
      bone.

PMID- 16636339
TI  - Irinogenetics: what is the right star?

PMID- 16636340
TI  - Genes associated with breast cancer metastatic to bone.
AB  - PURPOSE: The biology of tumors relapsing to bone is poorly understood. In this
      study, we initiated a search for genes that are implicated in tumors relapsing to
      bone in breast cancer. PATIENTS AND METHODS: We analyzed 107 primary breast
      tumors in patients who were all lymph node negative at the time of diagnosis and
      all had experienced relapse. Total RNA isolated from frozen tumor samples was
      used to gather gene expression data using oligo microarrays. RESULTS: A panel of
      69 genes was found significantly differentially expressed between patients who
      experienced relapse to bone versus those who experienced relapse elsewhere in the
      body. The most differentially expressed gene, TFF1, was confirmed by quantitative
      reverse transcriptase polymerase chain reaction in an independent cohort (n =
      122; P = .0015). Our differentially expressed genes, combined with a recently
      reported gene set relevant to tumors relapsing to bone in an animal model system,
      pointed to the involvement of the fibroblast growth factor receptor signaling
      pathway in preference of tumor cells that relapse to bone. Given that patients
      who experience relapse to bone may benefit from bisphosphonate therapy, we
      developed a classifier of 31 genes, which in an independent validation set
      correctly predicts all tumors relapsing to bone with a specificity of 50%.
      CONCLUSION: Our study identifies a panel of genes relevant to bone metastasis in
      breast cancer. The subsequently developed classifier of tumors relapsing to bone
      could, after thorough confirmation on an extended number of independent samples,
      and in combination with our previously developed high-risk profile, provide a
      diagnostic tool for the recommendation of adjuvant bisphosphonate therapy in
      addition to endocrine therapy or chemotherapy.

PMID- 16636341
TI  - Phase II placebo-controlled randomized discontinuation trial of sorafenib in
      patients with metastatic renal cell carcinoma.
AB  - PURPOSE: This phase II randomized discontinuation trial evaluated the effects of
      sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and
      vasculature, on tumor growth in patients with metastatic renal cell carcinoma.
      PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice
      daily during the initial run-in period. After 12 weeks, patients with changes in
      bidimensional tumor measurements that were less than 25% from baseline were
      randomly assigned to sorafenib or placebo for an additional 12 weeks; patients
      with > or = 25% tumor shrinkage continued open-label sorafenib; patients with >
      or = 25% tumor growth discontinued treatment. The primary end point was the
      percentage of randomly assigned patients remaining progression free at 24 weeks
      after the initiation of sorafenib. RESULTS: Of 202 patients treated during the
      run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients
      with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or
      placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were
      progression free versus 18% of the placebo-treated patients (P = .0077). Median
      progression-free survival (PFS) from randomization was significantly longer with
      sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29
      weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was
      readministered in 28 patients whose disease progressed on placebo; these patients
      continued on sorafenib until further progression, for a median of 24 weeks.
      Common adverse events were skin rash/desquamation, hand-foot skin reaction, and
      fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.
      CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic
      renal cell carcinoma and is tolerable with chronic daily therapy.

PMID- 16636342
TI  - Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic
      prognostic score.
AB  - PURPOSE: Although peripheral T-cell lymphoma, unspecified (PTCL/U), is the most
      common T-cell tumor in Western countries, no study to date has been based on the
      application of a wide panel of markers to a large series of patients and assessed
      the impact of phenotype on survival. We evaluated the expression of 19 markers in
      148 PTCLs/U and 45 PTCLs of the angioimmunoblastic type (AILD). PATIENTS AND
      METHODS: The analysis was performed on tissue microarrays by immunohistochemistry
      and in situ hybridization. Clinical data were available in 93 PTCL/U patients,
      most of whom had been included in a previous study proposing a prognostic index
      (PIT). RESULTS: An aberrant phenotype with frequent loss of CD5 and/or CD7 was
      typical for PTCLs, irrespective of whether they were U or AILD. Aberrantly
      expressed proteins rarely included CD20, CD15, and CD30. Positivity for Epstein
      Barr virus-associated small RNAs and CD15 expression emerged as adverse
      prognostic factors. Among PTCLs/U, the proliferation-associated protein Ki-67
      turned out to be prognostically relevant and was integrated in a new predictive
      score, incorporating age (> 60 years), high lactate dehydrogenase, poor
      performance status, and Ki-67 > or = 80%. This score was associated with the
      patient outcome (P < .0001) and was found to be more robust than PIT (P = .0043)
      in the present series. CONCLUSION: Our retrospective analysis shows a wide range
      of protein expression in PTCLs and proposes a new prognostic index. The latter
      represents one of the first examples of mixed score (including patient- and tumor
      specific factors) applied to malignant lymphomas and may be the basis for future
      prospective therapeutic trials.

PMID- 16636343
TI  - 11C-acetate positron emission tomography imaging and image fusion with computed
      tomography and magnetic resonance imaging in patients with recurrent prostate
      cancer.
AB  - PURPOSE: To assess the clinical value of computed tomography (CT) and magnetic
      resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission
      tomography (PET) imaging for detection and exact location of clinically occult
      recurrences. PATIENTS AND METHODS: Fifty prostate cancer patients with
      elevated/increasing serum prostate-specific antigen levels after radical therapy
      underwent whole-body AC PET. Uptake was initially interpreted as normal,
      abnormal, or equivocal. In case of abnormal or equivocal uptake, additional
      conventional imaging techniques, such as CT, MRI, and bone scans, were performed.
      To precisely define the anatomic location of abnormal uptake and to improve
      characterization of equivocal lesions, a software-assisted image fusion (CT-PET,
      MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n =
      37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional
      histopathologic evaluation was available. RESULTS: In five (10%), 13 (26%), and
      32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as
      normal, equivocal, and abnormal, respectively. Image fusion changed
      characterization of equivocal lesions as normal in five (10%) of 51 sites and
      abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of
      abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient
      management in 14 (28%) of 50 patients. CONCLUSION: Retrospective fusion of AC PET
      and CT/MRI is feasible and seems to be essential for final diagnosis. This is
      particularly true in patients with AC uptake in the prostate region.

PMID- 16636344
TI  - Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and
      treatment outcome in patients with non-small-cell lung cancer treated with
      irinotecan and cisplatin.
AB  - PURPOSE: To determine whether uridine diphosphate-glucuronosyltransferase 1A1,
      UGT1A7, and UGT1A9 polymorphisms affect the pharmacokinetics (PK) of irinotecan
      and treatment outcome of Korean patients with advanced non-small-cell lung cancer
      (NSCLC). METHODS: Eighty-one patients with advanced NSCLC were treated with
      irinotecan (80 mg/m2) on day 1 and 8 and cisplatin (60 mg/m2) on day 1
      intravenously of each 3-week cycle. Genomic DNA was extracted from peripheral
      blood and genotyped using direct sequencing. We analyzed the association of UGT1A
      genotypes with irinotecan PK and clinical outcomes. All statistical tests were
      two-sided. RESULTS: In genotype-PK association analysis, UGT1A1*6/*6 (n = 6),
      UGT1A7*3/*3 (n = 6), and UGT1A9-118(dT)9/9 (n = 11) were associated with
      significantly lower area under the time-concentration curve (AUC) SN-38G to SN-38
      (AUC(SN-38G)/AUC(SN-38)) ratio (P = .002, P = .009, and P = .001, respectively).
      In linkage disequilibrium analysis, the UGT1A7 variants were highly linked with
      the UGT1A1*6 (D' = 0.85, r2 = 0.63) and UGT1A9*22 (D' = 0.95, r2 = 0.88), which
      was substantiated in haplotype analysis. Patients with UGT1A1*6/*6 had lower
      tumor response and higher incidence of severe neutropenia. UGT1A9-118(dT)9/9 also
      showed a trend for high incidence of severe diarrhea, but not tumor response. In
      survival analysis, patients with UGT1A1*6/*6 had significantly shorter
      progression-free survival (P = .001) and overall survival (P = .017). CONCLUSION:
      These findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for
      SN-38 glucuronidation and associate with irinotecan-related severe toxicity.
      Specifically, UGT1A1*6 might be useful for predicting tumor response and survival
      outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy.

PMID- 16636345
TI  - Short-term effectiveness of hyperthermia for supraspinatus tendinopathy in
      athletes: a short-term randomized controlled study.
AB  - BACKGROUND: Hyperthermia has been introduced as a physical therapy modality for
      soft tissue injuries. HYPOTHESIS: The authors tested the null hypothesis that
      there are no short-term differences after the use of hyperthermia, ultrasound,
      and exercises for tendinopathy of the supraspinatus tendon. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: The authors studied
      37 athletes (29 men, 8 women; mean age, 26.7 +/- 5.8 years; range, 19-43 years)
      with supraspinatus tendinopathy who had had symptoms between 3 and 6 months.
      Subjects were randomly assigned to 3 groups. Group A (n = 14) received
      hyperthermia at 434 MHz. Group B (n = 12) received continuous ultrasound at 1 MHz
      at an intensity of 2.0 w/cm(2) 3 times a week. Group C (n = 11) undertook
      exercises, consisting of pendular swinging and stretching exercises 5 minutes
      twice a day every day. All interventions were undertaken for 4 weeks. Subjects
      were evaluated at baseline, immediately on completion of treatment, and at 6
      weeks after the end of the intervention using mean pain score for pain at night,
      during movement, and at rest on a visual analog scale; pain on resisted movement
      and painful arc on active abduction between 40 degrees and 120 degrees on a 4
      point scale; and Constant score. RESULTS: Patients who received hyperthermia
      experienced significantly better pain relief than did patients receiving
      ultrasound or exercises: group A, 5.96 to 1.2 (P = .03); group B, 6.3 to 5.15 (P
      = .10); group C, 6.1 to 4.9 (P = .09). CONCLUSION: Hyperthermia at 434 MHz
      appears safe and effective in the short term for the management of supraspinatus
      tendinopathy.

PMID- 16636346
TI  - Meniscal allograft transplantation in the sheep knee: evaluation of
      chondroprotective effects.
AB  - BACKGROUND: Early protection of articular cartilage, before degenerative changes
      appear on radiographs, should result in better long-term results, but scientific
      evidence regarding the effectiveness of meniscal transplantation is lacking.
      PURPOSE: To assess the chondroprotective effects of a new meniscal allograft
      transplantation animal model and evaluate a magnetic resonance imaging parameter,
      T2 mapping, in articular cartilage after meniscectomy and meniscal
      transplantation. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-five
      skeletally mature sheep were placed into 3 surgical groups: lateral meniscectomy
      (n = 24), meniscal allograft transplant (n = 17), and sham (n = 4). Animals were
      sacrificed at 2, 4, or 12 months. Cartilage was assessed by gross inspection,
      magnetic resonance imaging, T2 mapping, biomechanical testing, and
      semiquantitative histologic analysis. RESULTS: There were no differences between
      the sham operation and nonoperated control limbs. Compared with control limbs,
      meniscectomy resulted in significant increases in cartilage degeneration by all
      objective criteria (P < .01). Compared with meniscectomy, meniscal allograft
      transplantation resulted in significant decreases in cartilage degeneration (P <
      .02). There were significant correlations between T2-mapping data and all other
      traditional outcomes measures (P < .05, r(2) = 0.37-0.67). Compared with the
      nonoperated control limbs, allograft transplants demonstrated no significant
      differences at 2 months in any category, except magnetic resonance imaging data.
      By 4 months, nonoperated control limbs demonstrated significantly less wear
      compared to allograft limbs in all categories except modified Mankin scores.
      CONCLUSION: This model demonstrated significant chondroprotection compared with
      meniscectomy but demonstrated more cartilage wear at 4 months compared to control
      limbs. A high degree of allograft cell viability and vascular ingrowth was seen
      in allograft explants. T2 mapping may provide an accurate noninvasive measure of
      early cartilage degeneration after meniscectomy, as well as cartilage protection
      after meniscal allograft transplantation. CLINICAL RELEVANCE: This study
      establishes a reliable animal model for meniscal allograft transplantation and
      provides evidence for the utility of T2 mapping at clinically relevant magnetic
      resonance imaging field strengths for evaluation of early cartilage degeneration.

PMID- 16636347
TI  - Retrograde drilling for osteochondral lesions of the talar dome.
AB  - BACKGROUND: For the treatment of osteochondral lesions of the talar dome without
      detachment of the cartilage, there is little information on whether
      transmalleolar drilling or retrograde drilling is more effective in terms of
      clinical and morphologic evaluations. HYPOTHESIS: Retrograde drilling may be more
      effective than transmalleolar drilling for lesions without cartilage detachment.
      STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Subjects were 30
      patients with lesions on 1 foot of grade 0 or I, determined according to a
      modified Pritsch classification system. Nineteen patients underwent
      transmalleolar drilling (TMD group), and 11 patients underwent retrograde
      drilling (RD group). Ankle arthroscopy was performed 1 year postoperatively to
      evaluate cartilage conditions. RESULTS: Arthroscopic findings revealed that in
      the TMD group, 11 lesions (57.9%) were unchanged (grade I), and 8 lesions (42.1%)
      had deteriorated from grade 0 to I; in the RD group, 3 lesions (27.2%) had
      improved from grade I to 0, and 8 (72.8%) were unchanged (2 grade 0 lesions and 6
      grade I lesions). There was a significant difference between the 2 groups in the
      distribution of cases that had improved, were unchanged, or had deteriorated (P <
      .0001). CONCLUSIONS: This study showed that compared with transmalleolar
      drilling, retrograde drilling for osteochondral lesions of the talar dome can
      improve the arthroscopic assessment of the lesions.

PMID- 16636348
TI  - The 6 degrees of freedom kinematics of the knee after anterior cruciate ligament
      deficiency: an in vivo imaging analysis.
AB  - BACKGROUND: Previous studies of knee joint function after anterior cruciate
      ligament deficiency have focused on measuring anterior-posterior translation and
      internal-external rotation. Few studies have measured the effects of anterior
      cruciate ligament deficiency on 6 degrees of freedom knee kinematics in vivo.
      OBJECTIVE: To measure the 6 degrees of freedom knee kinematics of patients with
      anterior cruciate ligament deficiency. STUDY DESIGN: Controlled laboratory study.
      METHODS: The knee joint kinematics of 8 patients with unilateral anterior
      cruciate ligament rupture was measured during a quasi-static lunge. Kinematics
      was measured from full extension to 90 degrees of flexion using imaging and 3
      dimensional modeling techniques. The healthy, contralateral knee of each patient
      served as a control. RESULTS: Anterior cruciate ligament deficiency caused a
      statistically significant anterior shift (approximately 3 mm) and internal
      rotation of the tibia (approximately 2 degrees ) at low flexion angles. However,
      ligament deficiency also caused a medial translation of the tibia (approximately
      1 mm) between 15 degrees and 90 degrees of flexion. CONCLUSION: The medial shift
      of the tibia after anterior cruciate ligament deficiency might alter contact
      stress distributions in the tibiofemoral cartilage near the medial tibial spine.
      These findings correlate with the observation that osteoarthritis in patients
      with anterior cruciate ligament injuries is likely to occur in this region.
      CLINICAL RELEVANCE: The data from this study suggest that future anterior
      cruciate ligament reconstruction techniques should reproduce not only anterior
      stability but also medial-lateral stability.

PMID- 16636349
TI  - Exercise-related leg pain in female collegiate athletes: the influence of
      intrinsic and extrinsic factors.
AB  - BACKGROUND: Exercise-related leg pain is a common complaint among athletes, but
      there is little evidence regarding risk factors for this condition in female
      collegiate athletes. PURPOSE: To examine prospectively the effect of selected
      extrinsic and intrinsic factors on the development of exercise-related leg pain
      in female collegiate athletes. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Subjects were 76 female collegiate athletes participating in fall season
      sports, including cross-country running, field hockey, soccer, and volleyball.
      Athletes were seen for a pre-season examination that included measures of height,
      weight, foot pronation, and calf muscle length as well as a questionnaire for
      disordered eating behaviors. Body mass index was calculated from height and
      weight (kg/m(2)). Those athletes who developed exercise-related leg pain during
      the season were seen for follow-up. All athletes who developed the condition and
      a matched group without such leg pain underwent bone mineral density and body
      composition testing. Statistical analyses of differences and relationships were
      conducted. RESULTS: Of the 76 athletes, 58 (76%) reported a history of exercise
      related leg pain, and 20 (26%) reported occurrence of exercise-related leg pain
      during the season. A history of this condition was strongly associated with its
      occurrence during the season (odds ratio, 13.2). Exercise-related leg pain was
      most common among field hockey and cross-country athletes and least common among
      soccer players. There were no differences between athletes with and without such
      leg pain regarding age, muscle length, self-reported eating behaviors, body mass
      index, menstrual function, or bone mineral density. Athletes with exercise
      related leg pain had significantly (P < .05) greater navicular drop compared with
      those without. CONCLUSION: Exercise-related leg pain was common among this group
      of female athletes. The results suggest that there are certain factors, including
      foot pronation, sport, and a history of this condition, that are associated with
      an increased risk of exercise-related leg pain.

PMID- 16636350
TI  - Medial opening wedge tibial osteotomy and the sagittal plane: the effect of
      increasing tibial slope on tibiofemoral contact pressure.
AB  - BACKGROUND: Altering the tibial slope in an anterior cruciate ligament-deficient
      knee has been shown to affect anterior-posterior tibial translation. The effects
      on articular contact pressure of altering tibial slope during a high tibial
      osteotomy are unknown. HYPOTHESES: Performing an opening wedge osteotomy anterior
      to the midaxial line will increase tibial slope. Increasing tibial slope with a
      high tibial osteotomy in an anterior cruciate ligament-deficient knee
      redistributes tibiofemoral joint contact pressures onto the posterior tibial
      plateau. STUDY DESIGN: Controlled laboratory study. METHODS: Medial opening wedge
      high tibial osteotomies were performed, and a plate fixation with a known
      diameter inset was placed along the medial tibia in an anterior position and a
      posterior position on 9 cadaveric knees. Medial and lateral tibiofemoral contact
      pressures were measured at the resulting 2 different tibial slopes in both
      ligament-intact and ligament-deficient states using thin electronic sensors.
      RESULTS: Anterior plate application resulted in an increase in posterior tibial
      slope by an average of 6.6 degrees (P < .001) compared with posterior plate
      placement. After medial opening wedge high tibial osteotomy, the mean peak
      lateral tibiofemoral contact pressure (3.4 MPa) was significantly greater (P =
      .002) than was the mean peak medial pressure (2.6 MPa). In ligament-intact
      specimens, altering the tibial slope did not significantly shift peak contact
      pressures. However, in ligament-deficient knees, increasing tibial slope by an
      average of 5.5 degrees significantly redistributed the location of peak intra
      articular pressure, shifting it posteriorly by 24% (P = .003). CONCLUSION:
      Increasing tibial slope in anterior cruciate ligament-deficient knees with a high
      tibial osteotomy redistributes pressure into the posterior tibial plateau.
      CLINICAL RELEVANCE: In knees with chronic anterior cruciate ligament deficiency,
      posteromedial compartment degeneration is observed. Inadvertent redistribution of
      contact pressure into this area may be a cause of pain and premature clinical
      failure after medial opening wedge tibial osteotomy.

PMID- 16636351
TI  - Talar dome access for osteochondral lesions.
AB  - BACKGROUND: Recently, osteochondral grafting has become a popular procedure for
      treating challenging talar dome lesions. However, no guidelines exist for
      selection of the surgical approach to obtain perpendicular access to the talar
      dome. HYPOTHESIS: The majority of the talar dome can be accessed for
      perpendicular resurfacing procedures without need for osteotomy. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Nine human cadaveric ankles were dissected
      in a standard fashion to expose the talar dome. Seven approaches were used,
      including 4 arthrotomies (anteromedial, anterolateral, posteromedial, and
      posterolateral) and 3 osteotomies (anterolateral [Chaput], distal fibula, and
      medial malleolar). The area available for perpendicular access to the dome was
      determined for each approach. RESULTS: On average, 17% (range, 10%-24%) of the
      medial talar dome and 20% (range, 16%-25%) of the lateral talar dome could not be
      accessed without osteotomy. On the lateral aspect of the superior talar dome
      surface, an anterolateral osteotomy adds a mean of 22% to sagittal plane
      exposure. Malleolar osteotomies, when performed using the method described,
      provide access to the entire medial and lateral sides; however, there remains a
      mean residual 15% (range, 11%-38%) of the central talar dome that cannot be
      accessed in a perpendicular manner with any approach. CONCLUSION: Most of the
      talar dome can be accessed perpendicularly for resurfacing without malleolar
      osteotomy. Osteotomies substantially increase the access and are needed for
      extensive lesions. Part of the central portion of the talar dome is inaccessible
      to perpendicular resurfacing techniques with any standard approach. CLINICAL
      RELEVANCE: This study generated clear clinical guidelines to help decision making
      regarding the surgical approach to resurface the talar dome with osteochondral
      techniques. The majority of the talar dome can be accessed without osteotomy.

PMID- 16636352
TI  - Androgenic-anabolic steroids associated with mechanical loading inhibit matrix
      metallopeptidase activity and affect the remodeling of the achilles tendon in
      rats.
AB  - BACKGROUND: The indiscriminate use of anabolic-androgenic steroids has been shown
      to induce pathologic changes in the Achilles tendon in several situations.
      PURPOSE: To study tendon remodeling in rats treated with anabolic-androgenic
      steroids combined with an exercise program. STUDY DESIGN: Controlled laboratory
      study. METHODS: Wistar rats were grouped as follows: sedentary (group I),
      injected with anabolic-androgenic steroids only (group II), trained only (group
      III), and trained and injected with anabolic-androgenic steroids (group IV). The
      trained groups performed jumps in water: 4 series of 10 jumps each, with an
      overload of 50% to 70% of the animal's body weight and a 30-second rest interval
      between series, for 6 weeks. Anabolic-androgenic steroids (5 mg/kg) were injected
      subcutaneously. Activity of matrix metallopeptidases, a marker for tendon
      remodeling, was analyzed in tissue extracts by zymography on gelatin-sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: Morphological
      analyses of tendons showed that in group II, the most external layer that covers
      the tendon was thicker with aggregation of the collagen fibers, suggesting an
      increase in collagen synthesis. In group IV, an inflammatory infiltrate and
      fibrosis in tendons as well as a pronounced increase of the serum corticosterone
      level were observed. This training protocol upregulated matrix metallopeptidase
      activity, whereas anabolic-androgenic steroid treatment strongly inhibited this
      activity. The appearance of lytic bands with molecular masses of approximately 62
      and 58 kDa suggests the activation of matrix metallopeptidase-2. CONCLUSION:
      Anabolic-androgenic steroid treatment can impair tissue remodeling in the tendons
      of animals undergoing physical exercise by down-regulating matrix
      metallopeptidase activity, thus increasing the potential for tendon injury.
      CLINICAL RELEVANCE: Since the AAS abuse is so widespread, a better comprehension
      of the pathological effects induced by these drugs may be helpful for the
      development of new forms of therapy of AAS-induced lesions.

PMID- 16636353
TI  - Surgical repair of an acute latissimus dorsi tendon avulsion using suture anchors
      through a single incision.

PMID- 16636354
TI  - Tibiofemoral contact mechanics after serial medial meniscectomies in the human
      cadaveric knee.
AB  - BACKGROUND: There is no consensus regarding the extent of meniscectomy leading to
      deleterious effects on tibiofemoral contact mechanics. HYPOTHESIS: The meniscus
      aids in optimizing tibiofemoral contact mechanics, increasing contact area, and
      decreasing contact stress. STUDY DESIGN: Controlled laboratory study. METHODS:
      Twelve fresh-frozen human cadaveric knees each underwent 15 separate testing
      conditions-5 serial 20-mm posterior medial meniscectomy conditions (intact, 50%
      radial width, 75% radial width, segmental, and total meniscectomy) at 3 flexion
      angles (0 degrees , 30 degrees , and 60 degrees )-under an 1800-N axial load.
      Tekscan sensors were used to measure total force and medial force, contact area,
      mean contact stress, and peak contact stress. RESULTS: All posterior medial
      meniscectomy conditions resulted in significantly decreased contact areas and
      increased mean and peak contact stresses compared with the intact state (P <
      .05). The changes in contact mechanics after segmental and total posterior medial
      meniscectomies were not statistically different (P > .05). Incremental changes in
      contact area and mean contact stress increased as more peripheral portions of the
      medial meniscus were removed, whereas peak contact stresses exhibited similar
      incremental changes throughout all meniscectomy conditions. CONCLUSIONS: The
      meniscus is a crucial load-bearing structure, optimizing contact area and
      minimizing contact stress. Loss of hoop tension (ie, segmental meniscectomy) is
      equivalent to total meniscectomy in load-bearing terms. The peripheral portion of
      the medial meniscus provides a greater contribution to increasing contact areas
      and decreasing mean contact stresses than does the central portion, whereas peak
      contact stresses increase proportionally to the amount of meniscus removed.
      CLINICAL RELEVANCE: Because the degree of meniscectomy leading to clinically
      significant outcomes is unknown, a prudent strategy is to preserve the greatest
      amount of meniscus possible.

PMID- 16636355
TI  - Use of etomidate as an induction agent for rapid sequence intubation in a
      pediatric emergency department.
AB  - OBJECTIVES: Although etomidate is widely used for rapid sequence intubation
      (RSI), there is no consensus on the optimal induction agent and no prospective
      pediatric emergency department (ED) study exists. The objective of this study was
      to assess the effectiveness and safety of etomidate as an induction agent for RSI
      in the pediatric ED. METHODS: Data on RSI conditions and complications were
      collected prospectively on patients undergoing RSI in a tertiary pediatric ED
      from January 2003 to December 2003. ED hemodynamic data and inpatient data were
      collected retrospectively via chart review. RESULTS: Seventy-seven of 101
      patients requiring intubation underwent RSI with etomidate. The mean (+/- SD) age
      was 8.2 (+/- 6.2) years. All 77 patients were successfully intubated. Intubation
      condition data were available for 69 of 77 patients (89.6%). Conditions were good
      in 68 of 69 (99%; 95% confidence interval = 92.2% to 99.9%). The mean (+/- SD)
      maximal percent decrease in systolic blood pressure was 10% (+/- 13.6%). A
      greater than 20% maximal percent decrease in systolic blood pressure occurred in
      12 of 69 patients (17.4%; 95% confidence interval = 9.3% to 28.4%). There was no
      relationship between seizures after etomidate administration and prior seizure
      history (p = 0.25). Corticosteroids were given to 29 of 77 patients post-RSI for
      varying diagnoses. All eight patients given corticosteroids for shock were in
      shock at the time of intubation. CONCLUSIONS: In the pediatric ED setting,
      etomidate as an induction agent provided successful RSI conditions and resulted
      in varied hemodynamic changes that were especially favorable in those patients
      presenting in decompensated shock. Hypotension and seizures were uncommon and
      occurred in patients with confounding diagnoses. Until the significance of a
      single dose of etomidate on adrenal dysfunction is further clarified, caution
      should be used in those patients at risk for adrenal insufficiency.

PMID- 16636356
TI  - Portable advanced medical simulation for new emergency department testing and
      orientation.
AB  - OBJECTIVES: Efforts to mitigate unexpected problems during transition of an
      active emergency department (ED) to a new physical plant are imperative to ensure
      effective health care delivery and patient safety. The authors used advanced
      medical simulation (SIM) to evaluate the capacity of a new ED for emergent
      resuscitative processes and assist facility orientation before opening day.
      METHODS: Operational readiness testing and orientation to the new ED of a large
      academic center were arranged through a Transportable Enhanced Simulation
      Technologies for Pre-Implementation Limited Operations Testing (TESTPILOT)
      project. Using a portable life-sized computerized manikin, the project required
      participants to perform assorted patient care interventions on-site. Cardiac
      arrest, multitrauma, uroseptic shock, and pediatric toxicology scenarios elicited
      the dynamics of real-life ED activities. Debriefings and surveys assessed
      participants' perceptions of the new facility's clinical readiness and identified
      areas needing administrative attention. Subjective utility of SIM orientation was
      compared with that of standard facility orientation. RESULTS: Fourteen ED
      clinicians and five SIM facilitators participated over two sessions. The new
      facility received mean (+/- SD) and median five-point Likert scale scores of 4.4
      (+/- 0.8) and 5 for ability of clinical staff to perform resuscitations. The
      respective scores for ability of simulated scenarios to prepare staff for new ED
      function were 4.6 (+/- 0.5) and 5, compared with 4.2 (+/- 1.0) and 4 for non-SIM
      orientation (p = 0.22; not significant). Problems with equipment location,
      inadequate procedural surfaces, and insufficient orientation were discovered and
      rapidly corrected. CONCLUSIONS: Transportable SIM was used to evaluate the
      clinical functions of a new ED. Significant operational issues identified by
      participants were corrected before opening of the facility. Limited comparison
      did not reveal SIM enhancement of orientation.

PMID- 16636357
TI  - Automated external defibrillator program does not impair cardiopulmonary
      resuscitation initiation in the public access defibrillation trial.
AB  - OBJECTIVES: To evaluate whether automated external defibrillator (AED) training
      and AED availability affected the response of volunteer rescuers and performance
      of cardiopulmonary resuscitation (CPR) in presumed out-of-hospital cardiac arrest
      (OOH-CA) during the multicenter Public Access Defibrillation Trial. METHODS: The
      Public Access Defibrillation Trial recruited 1,260 facilities in 24 North
      American regional sites to participate in a trial addressing survival from OOH-CA
      when AED training and availability were added to a volunteer-based emergency
      response team. Volunteers at each facility were trained to perform either CPR
      alone (CPR) or CPR in conjunction with AED use (CPR+AED) according to randomized
      assignments. This study reports the frequency of response and initiation of CPR
      actions (chest compressions and/or ventilations) by volunteers in the CPR and
      CPR+AED study groups. RESULTS: A total of 314 presumed OOH-CA episodes occurred
      in CPR facilities, and 308 occurred in CPR+AED facilities. The volunteers were
      matched well for age, gender, and other features. Overall, ventilations (23.1%
      vs. 13.1%), chest compressions (24.4% vs. 12.1%), and both actions (19.8% vs.
      10.5%; all p < 0.05) were more commonly performed in OOH-CA cases in the CPR+AED
      group. However, when only OOH-CA cases with volunteers responding were analyzed,
      the rates of CPR actions were similar. In the subgroup of CPR+AED cases with a
      responding volunteer, the AED was turned on for only 47% of cases. Volunteers
      initiated a CPR action more commonly when the AED was turned on (60.7% vs. 39.3%;
      p = 0.003). CONCLUSIONS: In the Public Access Defibrillation Trial, rates of CPR
      actions for presumed OOH-CA victims were low but similar for CPR and CPR+AED
      responding volunteer rescuers. Factors associated with volunteer response, CPR
      action initiation, and AED activation warrant further investigation.

PMID- 16636358
TI  - A randomized, controlled trial of sucrose analgesia in infants younger than 90
      days of age who require bladder catheterization in the pediatric emergency
      department.
AB  - OBJECTIVES: To determine whether an oral sucrose solution improves pain response
      for infants undergoing bladder catheterization in an emergency department (ED)
      population. METHODS: A randomized, double-blinded study comparing the analgesic
      effects of a sucrose solution to placebo for infants < or = 90 days of age and
      requiring bladder catheterization. Infants with prior bladder catheterization,
      previous painful procedures that day, or neurological or genital abnormalities
      were excluded. Infants were assigned baseline pain scores and then given 2 mL of
      sucrose or water 2 minutes before catheterization. Trained pediatric ED nurses
      rated the infants for pain, presence of cry, and time to return to baseline.
      RESULTS: Eighty-three patients were enrolled; 40 were randomized to sucrose, and
      40, to placebo. Baseline pain scores were similar within each age group. Overall,
      sucrose did not produce a significant analgesic effect. In subgroup analysis,
      infants 1-30 days of age receiving sucrose showed a smaller change in pain scores
      (2.9 vs. 5.3, p = 0.035), were less likely to cry with catheterization (29% vs.
      72%, p = 0.008), and returned to baseline more rapidly after catheter removal (10
      seconds vs. 37 seconds, p = 0.04) compared with infants who received placebo.
      Infants older than 30 days of age who received sucrose did not show statistically
      significant differences in pain scores, crying, or time to return to baseline
      behavior. CONCLUSIONS: There was no overall treatment effect when using an oral
      sucrose solution before bladder catheterization in infants younger than 90 days
      of age. However, infants younger than or equal to 30 days of age who received
      sucrose had smaller increases in pain scores, less crying, and returned to
      baseline more rapidly than infants receiving placebo. Older infants did not show
      an improved pain response with oral sucrose.

PMID- 16636359
TI  - Emergency medicine research directors and research programs: characteristics and
      factors associated with productivity.
AB  - BACKGROUND: Periodic surveys of research directors (RDs) in emergency medicine
      (EM) are useful to assess the specialty's development and evolution of the RD
      role. OBJECTIVES: To assess associations between characteristics and research
      productivity of RDs and EM programs. METHODS: A survey of EM RDs was developed
      using the nominal group technique and pilot tested. RDs or surrogate respondents
      at programs certified by the Accreditation Council for Graduate Medical Education
      were contacted by e-mail in early 2005. The survey assessed programs' research
      infrastructure and productivity, as well as RD characteristics, responsibilities,
      and career satisfaction. Three measures of research productivity were empirically
      defined: research publications, grant awards, and grant revenue. RESULTS:
      Responses were received from 86% of 123 EM programs. Productivity was associated
      with the presence of nonclinical faculty, dedicated research coordinators, and
      reduced clinical hours for research faculty. Programs with an RD did not have
      greater research productivity, using any measure, than those without an RD. The
      majority of RDs cited pursuing their own studies, obtaining funding, research
      mentoring, and research administration to be major responsibilities. The majority
      characterized internal research funding, grant development support, and support
      from other faculty as inadequate. Most RDs are satisfied with their careers and
      expect to remain in the position for three or more years. CONCLUSIONS: Research
      productivity of EM residency programs is associated with the presence of
      dedicated research faculty and staff and with reduced clinical demands for
      research faculty. Despite perceiving deficiencies in important resources, most
      RDs are professionally satisfied.

PMID- 16636360
TI  - Hyperbaric oxygen reduces acetaminophen toxicity and increases HIF-1alpha
      expression.
AB  - OBJECTIVES: To investigate the effect of hyperbaric oxygen (HBO2) on
      acetaminophen (APAP)-induced hepatotoxicity. The authors further evaluated the
      effects of APAP poisoning and HBO2 on the expression and function of hypoxia
      inducible factor 1-alpha (HIF-1alpha) in an effort to further describe the
      mechanisms of APAP-induced hepatotoxicity. In vitro assays were performed to
      better understand the effects of HBO2 on HIF-1alpha function. METHODS: In vivo,
      four groups of C57BL/6 mice were treated as follows: APAP only, APAP followed by
      HBO2, HBO2 only, and untreated shams. Plasma alanine aminotransferase activity
      was measured, and hepatic HIF-1alpha induction was determined by Western blot. In
      vitro, cultured HEP G2 hepatocytes were exposed to HBO2, hypoxia (2.5% O2), or
      normoxia. HIF-1alpha DNA-binding and transcriptional activity were assessed.
      RESULTS: Alanine aminotransferase activity was reduced in the APAP+HBO2 group
      (2,606 IU/L +/- 4,080; vs. APAP: 6,743 +/- 3,397, p = 0.01 at 6 hours). APAP
      only, HBO2-only, and APAP+HBO2 treatments all increased HIF-1alpha expression
      relative to shams (p = 0.02, p = 0.02, and p < 0.01, respectively). HBO2
      increased HIF-1alpha DNA binding 5.7 (+/- 1.2)-fold relative to controls (p <
      0.01); however, a parallel increase in HIF functional transcriptional activity
      did not occur. CONCLUSIONS: Hyperbaric oxygen reduced early APAP-induced
      hepatocellular injury. APAP poisoning increases HIF-1alpha protein levels and
      functional activity. HBO2 increases HIF-1alpha protein levels and DNA binding
      without a corresponding increase in transcriptional activity.

PMID- 16636361
TI  - Reliability of a core competency checklist assessment in the emergency
      department: the Standardized Direct Observation Assessment Tool.
AB  - OBJECTIVES: A Council of Emergency Medicine Residency Directors task force
      developed the Standardized Direct Observation Assessment Tool (SDOT), a 26-item
      checklist assessment tool to evaluate Accreditation Council for Graduate Medical
      Education resident core competencies by direct observation. Each of the checklist
      items is assigned to one or more of five core competencies. The objective of this
      study was to test the interrater measurement properties of the SDOT instrument.
      METHODS: Two videos of simulated patient-resident-attending physician encounters
      were produced. Academic emergency medicine faculty members not involved in the
      development of the form viewed the two encounters and completed the SDOT for
      each. Faculty demographic data were collected. Data were collected from 82
      faculty members at 16 emergency medicine residency programs. The checklist items
      were used to generate a composite score for each core competency of patient care,
      medical knowledge, interpersonal and communication skills, professionalism, and
      systems-based practice. RESULTS: Univariate analysis demonstrated a high degree
      of agreement between evaluators in evaluating residents for both videos.
      Multivariate analysis found no differences in rating by faculty when examined by
      experience, academic title, site, or previous use of the SDOT. CONCLUSIONS:
      Faculty from 16 emergency medicine residency programs had a high interrater
      agreement when using the SDOT to evaluate resident core competency performance.
      This study did not test the validity of the tool. This data analysis is mainly
      descriptive, and scripted video scenarios may not approximate direct observation
      in the emergency department.

PMID- 16636362
TI  - The impact of chronic venous insufficiency and leg function on the quality of
      life of HIV-positive persons.
AB  - Chronic venous insufficiency and subsequent difficulties in leg function are
      causally linked to injection drug use and quality of life. Because injection drug
      use is a risk factor for human immunodeficiency virus infection, chronic venous
      insufficiency would be expected to occur with a higher prevalence in HIV-positive
      persons, yet the impact of chronic venous insufficiency on quality of life has
      not been investigated in this population. A cross-sectional design with quota
      sampling was used to enroll 73 HIV-positive participants-- 46 injection drug
      users and 27 non-injection drug users -- in this quality-of-life study.
      Questionnaires were read to participants and their legs were assessed for
      evidence of chronic venous insufficiency. Leg function scores, comprising
      assessment of leg pain, interference, and difficulty in using legs, were
      significantly related (P <.05) to quality-of-life scores, controlling for
      comorbid health problems. Chronic venous insufficiency, injection drug use, and
      leg function were interrelated. The legs of HIV-positive persons who have
      injected drugs should be assessed for manifestations of chronic venous
      insufficiency and other functional impairments. Further research involving a
      larger sample and assessment of chronic venous insufficiency treatments,
      including quality of life and leg function in HIV-positive persons, is needed.

PMID- 16636363
TI  - Colocutaneous fistula management in a dehisced wound: a case study.
AB  - A fistula is an abnormal opening between two or more organs or structures. Wound
      drainage containment is a key component of nonsurgical fistula management and may
      include pouches, skin barriers, transparent dressings, troughing procedures,
      saddle bagging, bridging, and condom and suction catheters used in combination
      with complex or routine pouching. Following extensive abdominal surgery, the
      wound of a 50-year-old woman dehisced and a colocutaneous fistula formed inside
      the wound. The wound containing the fistula, which was draining liquid stool, was
      too large for existing commercial pouching systems. When initial management
      efforts, including negative pressure wound therapy, failed to achieve containment
      goals, clinicians adapted the negative pressure wound therapy dressing to
      surround the fistula, which helped facilitate therapy while providing a platform
      for an ostomy appliance to contain the fistula drainage. The system was changed
      every 2 days until discharge. The wound and fistula management combination
      improved patient comfort and mobility, facilitated healing, and reduced patient
      dietary restrictions.

PMID- 16636364
TI  - Using horsechestnut seed extract in the treatment of venous leg ulcers: a cost
      benefit analysis.
AB  - Venous leg ulcers affect approximately 0.6% of the western population, consuming
      millions of healthcare dollars every year. To determine whether an alternative
      venous ulcer treatment using horsechestnut seed extract-- Aesculus hippocastanum-
      and conventional therapy involving dressings and compression was more cost
      effective than using conventional therapy alone, a 12-week cost-benefit analysis
      of horsechestnut seed extract therapy was conducted. The study, using data from a
      12-week prospective, randomized, placebo-controlled trial conducted in South
      Australia in 2002-2004, involved 54 patients with venous ulceration who received
      treatment through a large South Australian district nursing service. Taking into
      account the cost of horsechestnut seed extract, dressing materials, travel, staff
      salaries, and infrastructure for each patient, horsechestnut seed extract therapy
      combined with conventional therapy was found to be more cost-effective than
      conventional therapy alone with an average savings of AUD 95 in organizational
      costs and AUD 10 in dressing materials per patient. This study confirms that
      dressing change frequency has a significant impact on the total cost of wound
      care and suggests that district nursing service operation efficiency may be
      enhanced through the use of horsechestnut seed extract as a result of less
      frequent nursing visits. Further study of this treatment modality is warranted.

PMID- 16636365
TI  - Managing ichthyosis: a case study.
AB  - Ichthyoses-- rare, genetic, incurable dermatologic diseases characterized by dry,
      thickened, scaling skin-- affect more than 1 million Americans and can cause
      devastating disfigurement with numerous physical, social, and emotional
      consequences. Topical treatments typically focus on symptom management. A 44-year
      old man presented with severe X-linked type ichthyosis. When his condition did
      not improve with the use of a variety of topical and systemic treatments, a once
      a-day, over-the-counter skin care regimen consisting of a surfactant-free
      cleanser followed by the application of moisturizer containing amino acids,
      vitamins, antioxidants, and methylsulfonylmethane was prescribed. After 4 weeks
      of using this management regimen on a test area on his left arm, the skin was
      clear and discomfort and itching had subsided. Subsequent application of the skin
      care products on other affected areas also did not cause any adverse reactions
      and his skin continued to improve. Symptom resolution and patient satisfaction
      indicate the product line may be a viable consideration for use in patients with
      similarly compromised skin.

PMID- 16636367
TI  - [The post-closure syndromes of the duodenal ulcers].
AB  - The objective of the study was the determination of the ulcerorhaphy in
      perforated duodenal ulcers, a clinical course of the disease in the post
      operational period and a delineation of the treatment tactics in the case of
      various morpho-functional abnormalities in the post-ulcerorhaphic period. To this
      effect, the method of retrospective analysis, allowing comparison of the pre- and
      post- operational pictures of the disease has been applied. As a result the post
      closure syndromes of the perforated ulcer were detected in 42 (37,9%) patients.
      In the case of the presence of the syndrome, the disease is aggressive, emerging
      as a recurrent refractive ulcer and various severe complications. This kind of
      the disease is resistant to a conservative therapy, thus, requiring a drastic
      surgery.

PMID- 16636366
TI  - Managing a traumatic wound in a geriatric patient.
AB  - Clinical management of a wound in a geriatric patient requires an understanding
      of age-related changes in the skin and the knowledge to make appropriate
      treatment choices. This case study describes clinical assessment and management
      of a traumatic hip wound in a 75-year-old patient. In addition to addressing his
      nutritional status by providing supplements, topical wound care preparations,
      including papain-urea and castor oil/balsam of Peru/trypsin, were used as a
      conservative approach to address debridement and periwound skin concerns. Extra
      vigilance is required to assess wounds in geriatric patients to determine proper
      wound treatment and achieve optimum results. Additional studies to evaluate
      optimal treatment strategies in the clinical management of traumatic wounds in
      the geriatric population are needed.

PMID- 16636368
TI  - [Modern aspects of surgical treatment of pulmonary bullose emphysema].
AB  - 32 patients (2 females and 32 males) with bilateral pulmonary bullose emphysema
      have been treated in Acad.. Z. Tskhakaia Thoracoabodminal clinic from 1998
      through 2004. Age varied from 17 to 64 years. In 4 cases diffused emphysema
      observed, 17 patients were presented with gigantic bullas varied in size from 120
      to 150 mm with most of them located in the upper lobes. All patients underwent
      preoperative full range radiology study including CT scan, in 17 cases an
      additional gamascintygraphy was utilized. 19 patients underwent lung preserving
      bilateral resection through transsternal approach. In 6 cases surgery was
      performed by bilateral video assisted mini thoracotomy route. In 7 cases
      bilateral operation was performed by thoracotomy on one side and thoracoscopy on
      another. In this series neither morbidity nor mortality was observed.

PMID- 16636369
TI  - [Peculiarities of wound infections in severe burns].
AB  - Infections in patients with burns remain as a one of the main unsolved problems.
      The present work is based on the analysis of the data obtained from the 642
      patients with burns (adults and children) during 2000-2005. The staphylococcus
      infection is still the leading. At the same time the percent of the gram-positive
      infection increased. The basic risks-factors that promote the development of the
      nosocomial infection in the case of burns were revealed. The antibacterial
      therapy in the severely burned patients has to be based on the individual
      peculiarities of an every patient. The more severe pathology the less possibility
      using the standard regimen. The short and ultra-short preventive antibiotic in
      the patients with severe burns are unacceptable. The "step-by-step", escalation
      returnable tactics of antibiotics administration has justified itself.

PMID- 16636370
TI  - Comparison of surgical and by transcatheter methods of closure of atrial septal
      defect based on the two year experience.
AB  - Our study was designed to compare surgical and transcatheter methods of treatment
      of frequent congenital malformation: atrial septal defect. Overall, during two
      year period 45 patients enrolled this study. 36 where referred to surgical
      treatment, 9 - to interventional. In most of the cases the choice of treatment
      method was made pre procedurally based on malformation anatomy. Both correction
      methods proved to be safe and effective. As our study shows the closure success
      rate is identical for both methods for appropriately selected patients. Residual
      shunts where haemodynamically insignificant and never needed re-operation. Both
      procedures have approximately similar major complication prevalence. The main
      differences were absence of the need for blood transfusion products, morbidity,
      and length of hospital stay, as well as the cost of treatment. All of them are in
      favour of Amplatzer device closure. Based on this information we can conclude
      that all patients feasible for transcatheter treatment should be treated by means
      of this procedure.

PMID- 16636371
TI  - Complications of nerve sparing retroperitoneal lymph node dissection.
AB  - Nerve sparing retroperitoneal lymph node dissection is standard treatment method
      for early stage non-seminomatous germ cell tumor. However, an alternative
      approaches (surveillance policy, adjuvant and primary chemotherapy) have
      approximately the same capability for cure. Therefore, the current debate is to
      decide which is less morbid for the patient at risk. We assessed associated
      complications of nerve sparing retroperitoneal lymph node dissection in 33
      patients (25 with clinical stage I and 8 with clinical stage IIA) treated at our
      center from June 1996 to November 2005. There were 7 (21%) complications (2
      intraoperative, 4 early minor and 1 early major) in 6 out of the 33 operated
      patients. There were no late complications. Antegrade ejaculation was preserved
      in 30 patients (91%). Postoperatively 19 out of 33 patients were classified as
      pathological stage I and 14 as pathological stage IIA. Both groups were balanced
      with respect to distribution of complications. The data indicate that nerve
      sparing RPLND is a well tolerated urologic procedure with a low early and no late
      morbidity.

PMID- 16636372
TI  - Clinical characteristics of prognostic factors in uterine endometrioid
      adenocarcinoma of various grade.
AB  - The aim of this study was to compare clinical characteristics of prognostic
      factors in uterine endometrioid adenocarcinoma of various grades. We have studied
      104 postmenopausal women with a histological diagnosis of uterine endometrioid
      adenocarcinoma. Staging and grading of primary tumor were done according to FIGO
      system. The following factors were examined: family history of cancer, presence
      of obesity and vaginal bleeding, recurrence rate within the two years of the
      study (disease-free periods), vessel permeation, muscle invasion (<1/3, 2/3,
      >2/3), cervical involvement, lymph node metastasis, ascites cell analysis,
      parametrium invasion, adnexal metastasis, CA125 pre-surgery values. Histological
      examination has showed grade 1 endometrioid adenocarcinoma in 35 cases (33,7%,
      group 1), grade 2 adenocarcinoma in 44 cases (42,3%, group 2), and grade 3
      adenocarcinoma in 25 cases (24%, group 3). Most of the factors we have examined
      seem to be associated with histological grade of uterine endometrioid carcinoma.
      The analysis of clinicopathological prognostic factors in G1 endometrioid
      adenocarcinoma cases has showed that about half of these patients are obese,
      vaginal bleeding is not common, no cervical involvement, parametrium invasion,
      adnexal metastasis and vessel permeation at the time of diagnosis, no recurrence
      within two years, pre-surgery value of CA125 is normal, and myometrial invasion
      is less than 1/3. G3 endometrioid adenocarcinoma cases have showed family history
      of endometrial cancer, more than half of the patients were obese, with uncommon
      vaginal bleeding and positive peritoneal cytology, but cervical involvement,
      parametrium invasion, adnexal metastasis and vessel permeation are present at the
      time of diagnosis, pre-surgery value of CA125 is high, and myometrial invasion is
      2/3 or more than 2/3 in majority of cases, furthermore, in some cases recurrent
      tumors were developed within two years. G2 endometrioid adenocarcinoma can be
      considered as an intermediary form which should be managed according to the
      clinical stage. The results lead to conclude that the histological grade of
      uterine endometrioid adeno carcinoma seems to be an important independent
      prognostic indicetor as it is strongly associated with other clinical
      pathological prognostic factors.

PMID- 16636373
TI  - [Breast cancer immunohistochemical features in different age groups].
AB  - We investigated 52 incidents of the breast cancer to determine their
      immunological profile in the different age groups. Breast tissue-specific and at
      the same time oncologically important immunohistochemical markers: estrogen- and
      progesterone receptors (ER, PR), oncoprotein HER-2/neu, protein PS2, markers of
      angiogenesis CD31 and mitotic activity Ki-67 were investigated. Patients were
      divided into 3 group: I - patients under 45 years (23), II - from 46 to 55 (14),
      III - 56 year and older (15). Investigations showed that expression of the
      immunohistochemical markers was dissimilar in the different age groups. In the I
      group of the estrogen- and progesterone receptors (ER, PR) and protein PS2 was
      lower, in contrast to the expression of HER-2/neu, CD31 and Ki-67 were higher
      then in the elder group. Expression of the estrogen- and progesterone receptors
      (ER, PR) and protein PS2 markers was increasing with the patient age, and
      significant decrease of the HER-2/neu, CD31 and Ki-67 was observed. This
      indicates that in younger patients cancer is more aggressive.

PMID- 16636374
TI  - [Interferon-gamma and neopterin in blood serum of patients with chronic
      periodontitis after autograft operations].
AB  - The aim of the study was to compare the serum levels of interferon-gamma (INF
      gamma) and neopterin (NPT) in 10 patients with mild form of chronic periodontitis
      before and after operations. Overall objective of these operations is the
      elimination of periodontal and osseous pockets. 10 blood donors were included in
      the control group. The serum levels of INF-gamma and NPT were measured using
      enzyme immunoassay technique. INF-gamma and neopterin in patients with chronic
      periodontitis were assessed before and 4 to 6 weeks after the operation. The mean
      serum INF-gamma in patients with mild form of chronic periodontitis (n=10) was
      13,2+/-4,03 pg/mL. The mean serum INF-gamma level in patients with mild form of
      chronic periodontitis (n=10) after the operations was 10,05+/-3,12 pg/mL. Serum
      levels of INF-gamma in patients with mild form chronic periodontitis were
      significantly higher than those in the control group. There was no significant
      difference in serum levels of INF-gamma in patients with mild form before and
      after operations. The mean serum level of NPT in the control was 5,3+/-2,39
      nmol/L. The mean serum NPT level in patients (n=10) with mild form chronic
      parodontitis was 14,4+/-10,05 nmol/L. After operations NPT concentration were
      reduced (6,9+/-3,39 nmol/L). Serum levels of NTP in patients with mild form
      chronic periodontitis were significantly higher than those in the control group.
      Significant difference was observed in serum levels of NPT in patients with mild
      form of chronic periodontitis before and after operations. Obtained data allow
      specifying the mechanism of positive influence of autograft operations on the
      pathogenesis of chronic periodontitis.

PMID- 16636375
TI  - [Efficient methods of prevention and treatment of permanent first molars before
      completion of root formation].
AB  - Examination of first molars among 124 children, age range 7-8 years, showed high
      intensity of caries disease. Detection and prevention of risk factors, also
      practical use of prevention and treatment methods existed in clinical
      stomatology, especially before completion of root formation of permanent teeth,
      is extremely important. Results showed that deep fluoridation of fissures of
      permanent teeth with enamel Hermetisation Liquid (A. Knappfost) is very effective
      method for preventing dental caries. Caries was reduced in 96% of cases.
      Cultivation of cavity with above-mentioned solution, right before restoration
      prevents reoccurrence of caries and pulpal complications that is very important
      for future growth and formation of roots of permanent teeth and for functional
      value of permanent teeth themselves.

PMID- 16636376
TI  - [Sensitivity and resistance of aerobic bacteria isolated from patients with
      periodontitis towards antibiotics and bacteriophages (comparative analysis)].
AB  - In order to examine sensitivity and resistance of isolated aerobic bacteria from
      periodontitis materials towards antibiotics and bacteriophages, there has been
      studied exudations taken from 737 patients' periodontic pockets or the tissue
      taken from curettage. According to the rate of identified microorganisms, they
      have been arranged as follows: S. epidermidis 39,34+/-1,56%; S. pyogenes 18,84+/
      1,25%; M. catarrhalis 17,09+/-1,2%; S. aureus 10,71+/-0,99%; E.coli-5,66+/-0,74%;
      Diphtheroids in 1,13+/-0,33%; S. Mucilaginosus 1,02+/-0,32%, proteus vulgaris -
      0,72+/-0,27%; H. parainfluenzae - 0,72+/-0,27%; S. intermedium 0,61+/-0,24%; P.
      aeruginosa - 0,61+/-0,24%; H. influenzae - 0,51+/-0,22%, S. saprophiticus -
      0,51+/-0,22%; S. viridans - 0,51+/-0,22%; S. pneumoniae - 0,41+/-0,2%; K.
      pneumoniae - 0,41+/-0,22%; S. haemoliticus - 0,41+/-0,2%; B. adolescentics -
      0,3+/-0,17%; L. acidophilus -0,3+/-0,17%; S. salivarius-0,1+/-0,1%. It has been
      stated that percentage of polyresistant strains is growing. While having aerobic
      infections of periodontitis, kefzol, cephazolin, cephamezin, zinaceph, klaphoran,
      cephdazidim (cephalosporins I, II, II generation); tetracycline, doxycycline,
      (tetracyclines); 5-noks, cyprophloxacyne (chinolons I, II generation);
      ryphamphcyne (rymphamicynes); but standby medicines may be also considered:
      penicillin G, procaine penicillin (penicillines); streptomycin, kanamicin,
      gentamicin (aminoglycosides); lincomycin, clindamycin, (lincosamides);
      eritromycin, macropen (macrolides); chloramphenicol. Since the resistance of
      microbial strains was not developed towards bacteriophages during the treatment
      it is considerable to apply simultaneously the bacteriophages and standby
      antibiotics.

PMID- 16636377
TI  - [Peculiarities of mandible fracture consolidation while applying different
      methods of treatment].
AB  - Purpose of the study was the photodensitometrical estimation of the efficiency of
      using kolapan granules in combination with the retabolil injection, during the
      osteosinthesis in the cases of mandible fracture. The operative treatment of
      patients was realized at the second day following the trauma. The Patients were
      divided into three groups: 1-st group (20 patients), where fixing was done by
      intermaxillar Tigerstadt device, in the 2-nd group (20 patients) osteosinthesis
      was carried out by the titanium miniplates ("LIM"), while in the 3-rd group (20
      patients) - osteosinthesis with the use of the same titanium miniplates ("LIM"),
      kollapan granules (the company "Intermedapatit") and intermuscular injection of
      retabolil (the company "Gedeon Richter") - 50mg (5%) was performed. Radiography
      was carried out in patients in standardized conditions, at the day of operations,
      at the 1-st, 4-th and 24-th weeks after trauma. From the gained results the
      significant advantage of osteosinthesis in combination with filling the defect by
      Kollapan granules and usage of retabolil in comparison with the intermaxillar
      fixation and usual osteosinthesis is obviously seen. The process of osteogenesis
      under such treatment is significantly faster.

PMID- 16636378
TI  - [Changes of immunological and cytogenetic indexes in lymphocytes of patients with
      bacterial endocarditis under the influence of laser therapy and a hyperbaric
      oxygen therapy].
AB  - The purpose of the present work was the estimation of the therapeutic effect of
      the soft laser therapy and a hyperbaric oxygen therapy during their inclusion in
      a therapeutic complex for the treatment of bacterial endocarditis. 30 patients
      (II group) under our observation have passed the standard basic therapy, and for
      45 patients (I group) of different age the intravenous laser and hyperbaric
      oxygenation were added into the therapeutic complex. The estimation was made by
      evaluation of immune status and cytogenetic markers before treatment. At the
      height of disease there was marked immune deficiency, basically at the expense of
      T-helpers, and also of the B- lymphocyte part. The phagocyte system efficiency
      indices were decreased. By the admission of patients in the clinic the number
      cells with aberrations of chromosomes was increased. After the treatment nn the I
      group of patients there was absolute and relative elevation on the number of T
      and B- lymphocytes, T- helpers, also the decrease of leukocytes, T-lymphocyte
      index, the increase of blast transformation lymphocytes level on mytogen FGA. The
      phagocytosis was activated, the balanced level of different Ig classes occurred.
      Number of cells with aberrations of chromosomes sharply decreased, basically at
      the expense of aneuploidic cells. Obtained results show, that laser therapy and
      hyperbaric oxygen therapy can be included in the therapeutic complex for the
      treatment of bacterial endocarditis.

PMID- 16636379
TI  - Relationship between coronary heart disease and chronic renal insufficiency.
AB  - Coronary heart disease (CHD) is a worldwide public health problem. CHD is 100
      times more prevalent than CHD with Chronic renal insufficiency (CRI), and its
      incidence is increasing at an even faster rate. The aim of this work is to
      determine the connection between CHD and risk factors in CHD patients with CRI.
      There were 78 patients (age 54,46+/-12,46 years), 45 males and 33 female. In
      group I were included 33 patients with CHD (57,7+/-9,03 years, in group II - 25
      patients with CHD and CRI (59,35+/-10,64 years). The control group III - was
      composed of practically healthy persons 20 (40,7+/-12,6 years). Lipid spectrum
      was studied in blood serum using "Janway 4500" spectrometry, by the enzyme method
      using "BIOLABO" test (France). The received data was treated statistically M+/
      SD(M-mean SD-standard deviation (SD). Student-t test was used for the analysis of
      the data obtained for the groups, statistical appearance was determined as
      p<0,05. Correlation was tested according to the Person's correlation. Data of our
      studies showed, that in group II level of lipid spectrum is lower than in group
      II. We suggested that these complex changes in lipid profiles may significantly
      contribute to the heavy pass CHD. Increased level of IA results from complex
      changes in lipid profiles. In group II the blood pressure (BP) is significantly
      (p<0,05) higher (172/94 mm/hg) than in group I (162/88 mm/hg). By literature a
      primary kidney defect can produce hypertension or increase a level of BP.
      According to our observation, dyslipidemia is significantly expressed in CHD
      patients with CRI, than without CRI. Data of our studies showed, that abnormal
      lipid spectrum is positively correlated with renal damage. Therefore, we can
      conclude CHD with CRI passes heavier than CHD without CRI.

PMID- 16636380
TI  - [Unexplained somatic symptoms and underlying psychologic disorders in the
      neurology clinic].
AB  - The aim of our study was to determine pseudoneurological symptoms (PNS) and
      related mental disorders among patients referred to the neurology clinic. All
      cases of somatoform disorders (SD) as main discharge diagnosis, made on the basis
      of neuropsychiatric interview after exclusion of neurological disease, have been
      retrospectively reviewed. Among 623 patients, hospitallized to the Institute of
      Neurology between 2000-2001 years, SD prevalence was 3,69%, where conversion
      disorder accounted for 69,6% and somatization disorder - for 13%. Mean age was
      27,8 (+/-10,1) and female/male ratio was 1,55. Results show that PNS appear to be
      a good marker of SD. We suggest that early detection of PNS would provide a
      correct management of patients.

PMID- 16636381
TI  - Predicting value of cerebrospinal fluid proinflammatory factors in acute phase of
      ischemic stroke.
AB  - Study purposed to establish the correlation between proinflammatory cytokines'
      initial CSF levels and neurological outcome on 7th day of acute ischemic stroke.
      58 patients with acute ischemic stroke have been investigated. Neurological
      impairment assessed in 48 hours and on 7th day of stroke applying the
      international scales NIHSS and GCS. Patients divided into two groups: with severe
      stroke (GCS>9, NIHSS>15) and stroke with moderate severity (GCS=14,15; NIHSS=10
      15). On 7th day increase of NIHSS score and decrease of GCS score at least 1
      point was considered as deterioration and decrease of NIHSS score and increase of
      GCS score at least 1 point was considered as amelioration. CSF levels of
      proinflamatory cytokines determined using the enzyme-linked immunosorbent assay
      (ELISA). Control consisted with 15 patients, which were taken CSF in relation
      with vertebral discopathies. Means calculated by t-paired test. Pearson
      correlation and multivariate logistic regression were used. In 48 hours of stroke
      onset the CSF levels of interleukine-1beta (IL-1beta), interleukine-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) were elevated compared to control.
      Statistical differences were not found between groups regarding the initial CSF
      levels of IL-1beta and TNF-alpha (p<0,5), while the significant statistical
      differences were found in regard with IL-6 CSF levels (p<0,05) between groups and
      against control. Significant positive correlation was found between initial CSF
      IL-6 levels and ischemic lesion size and neurological outcome at 1 week as well
      (r=+0,48 p<0,05 and r=+0,54 p<0,01 respectively). Thus, the IL-6 CSF levels in
      acute stage of ischemic stroke might be considered as the relatively stable
      prognostic indicator of clinical course of the disease.

PMID- 16636382
TI  - [Optimisation issues of conservative treatment of neurological abnormalities in
      dystrophyc-degeneration processes of the vertebral column].
AB  - Basic method of treating diskogenic radiculopathy is surgical treatment, aim of
      which is to remove the disk hernia and the root compression. Traditional methods
      of therapy are of temporary character. The aim of our study was to search for
      alternative methods of treatment of diskogenic radiculopathy using glukosamin
      sulfate and chondroitin sulfate. 6 patients have been examined with the aid of
      clinical characteristics and spinal MRI, a diagnosis of lumbar diskopathy was
      stated. Treatment was carried out using glukosamin sulfate and chondroitin
      sulfate according to specific scheme. The paper includes two cases as
      illustrations. The observations carried out on the patients showed that a long
      term usage of glukosamin sulfate and chondroitin sulfate can serve as an
      alternative way of treating the diskogenic radiculopathy at least in some cases.
      On the other hand, it should be supposed that as a long-term course treatment
      with the glukosamin and chondroitin improves metabolism of cartilageous tissues
      and it can serve as a prevention measure for the reappearance of the pathological
      process.

PMID- 16636383
TI  - Hiv prevalence among high risk behavior group persons with herpes zoster
      infection.
AB  - The aim of the two year (2003-2005) study was to study the HIV prevalence among
      high risk behavior groups of persons with Herpes Zoster infection. For this
      purpose we have investigated the high risk group patients: 1257 prisoners (1st
      group), 1543 IDUs (2nd group) and 1350 persons including: homosexuals, persons
      with history of frequent unprotected sex and persons with hepatitis B and C (3rd
      group). We revealed the persons with current or previous history of Herpes
      Zoster, and studied HIV prevalence among them. Besides, we have studied the
      immune status of revealed HIV positive persons, relationship between disease
      (Herpes Zoster) severity and CD4 count. Herpes Zoster infection was diagnosed
      based on clinical symptoms, anamnesis and by detection of VZV specific IgM and
      IgG by ELISA. HIV infection was diagnosed by ELISA method and was confirmed by
      Western Blot. CD4 count was detected by immunophenotyping technique and was
      analyzed using a FACSCalibur flow cytometer. The total prevalence of HIV
      infection among high risk behavior group persons with Herpes Zoster infection was
      18,9% (31 HIV cases out of 164). The disease (Herpes Zoster) severity and
      duration was associated with decreased rate of cellular immunity, CD4 count.
      Herpes Zoster has a positive predictive value for HIV infection, predominantly
      recurrent Herpes Zoster. Herpes Zoster should be recognized as a marker condition
      indicating the necessity of screening for HIV, especially in Georgia, the region
      where the problem of IDU exists.

PMID- 16636384
TI  - [The prevalence of diabetic retinopathy in subjects with type 2 diabetes of one
      year and less duration].
AB  - Cases of diabetic retinopathy (DR) at the preclinical stage of diabetes mellitus
      type 2 (DMT2) can't be explained considering the conventional theory on etio
      pathogenesis of diabetic microangiopathy. The present research aimed to study the
      prevalence of DR among the patients with the newly diagnosed DMT2 and to analyze
      the possible causes of formation of this complication in the period preceding the
      period of hyperglycemia. According to the data of the present study the DR
      prevalence in the patients with newly diagnosed DMT2 equals to 16,4%. The chance
      of the existence of DR among the patients over 45 is 2,6 times higher than among
      those of 45 and younger. Proceeding from the results of the present study the
      assumption is made on the presence of pathogenic mechanisms conditioning
      initiation of diabetic microvascular pathology before stabilization of
      hyperglycemia at the stage of the impaired glucose tolerance.

PMID- 16636385
TI  - Creatine kinase mb, cardiac troponin T and cardiac troponin I as the markers of
      rhabdomyolysis in chronic hemodialysis patients.
AB  - We designed this study to compare serum markers of myocardial injury creatine
      kinase MB (CK-MB), as well, as serum contractile proteins, especially cardiac
      troponin T (cTnT) and cardiac troponin I (cTnI) in dialysis patients without
      acute ischemic heart disease. 24 patients on chronic hemodialysis were studied by
      history and physical examination, electrocardiography, and two-dimensional
      echocardiography. These patients had no evidence of ischemic heart disease.
      Biochemical markers were measured in serial predialysis blood samples with
      specific monoclonal antibody-based immunoassays. For several patients at least
      one sample measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA
      cTnT, 17 of 24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%).
      Chronic dialysis patients without acute ischemic heart disease frequently had
      increased serum CK-MB and cTnT. Our finding are in agreement with the conclusions
      that cTnT and CK-MB detected in the serum of patients on chronic hemodialysis
      originates from the skeletal muscle and not from the heart.

PMID- 16636386
TI  - [Effect of complex rehabilitation by physical factors (therapeutic mud, waves of
      millimeter range) on the indices of inflammation process and immune status in
      patients with traumas of peripheral nervous system].
AB  - 82 patients with traumas of peripheral nervous trunks (middle, ulnar, radial,
      tibular and tibial nerves) were investigated, including 44 persons with
      neuroapraxia of those trunks and 38 with axonotmesis. It was established that the
      patients with traumas of peripheral nervous trunks showed the presence of
      inflammatory process and sensitization of the body which was exposed in the
      reaction of precipitation at C-reactive protein with the increase of the content
      of serum glycoides and total nonspecific immunuglobulin E in blood serum. The
      investigated patients showed also decrease in nonspecific resistance of organism
      and change in immune status. All the above-referred shifts were more expressed at
      axonotmesis of peripheral nervous trunks. Rehabilitation with the use of Kumisi
      therapeutic mud and electro magneto field of millimeter range resulted decrease
      of inflammation process and body sensitization in patients with traumas of
      peripheral nervous trunks almost to disappearance of inflammation process and
      body sensitization. Such rehabilitation increased nonspecific resistance,
      normalized the indices of immune reactivity. The above-referred positive shifts
      were comparatively well expressed at neuroapraxia of peripheral nervous trunks.

PMID- 16636387
TI  - Electrocardiographic patterns and systolic and diastolic functions of the heart
      in the highly trained football players with increased left ventricular mass.
AB  - Over the past several years interest regarding the causes of sudden deaths in
      young trained athletes has heightened in the medical community. 36% of sudden
      cardiac death (SCD) in young competitive athletes is due to hypertrophic
      cadiomyopathy (HCM), while 10% of SCD cases in sports are due to increased
      cardiac mass without signs of HCM. The goal of this study was to evaluate
      systolic and diastolic functions, and to determine the clinical significance of
      electrocardiographic patterns in highly trained football players with increased
      left ventricular mass index (LVMI) > 125g/m(2). 221 highly trained male football
      players were studied, among them 46 with increased LVMI. M, 2D, Doppler
      echocardiography and resting and exercise electrocardiography were performed.
      Various cardiovascular abnormalities were found by echocardiography in 12
      athletes (5,4%). Systolic and diastolic functions of the heart were within normal
      limits. Increased left ventricular mass in the football players was often
      associated with abnormal ECG patterns (47,8%). Abnormal ECGs were found in 85,7%
      of football players with concentric hypertrophy. The group of athletes with both
      increased LVMI and abnormal ECG patterns need further evaluation and observation.
      ECG and echocardiography should be included in the PPS protocol of the highly
      trained football players to prevent SCD in young athletes.

PMID- 16636388
TI  - [Immunological parameters and ultrastructure of blood formed elements in
      nephrotic syndrome in children].
AB  - The aim of the study was the evaluation of significance of immunopathogenic
      mechanisms in the pathogenesis of minimal change nephrotic syndrome and the study
      of the ultrastructural changes of peripheral blood formed elements. The
      observation was carried out on 64 patients with steroid sensitive minimal change
      nephrotic syndrome. During the manifestation and recurrence of the disease, in
      the majority of the patients, the results of immunological studies revealed the
      reduction in both total and absolute count of T-lymphocytes on the background of
      decreased immunoregulatory index (T(4+)/ T(8+)). In the peripheral blood
      statistically reliable reduction in the percent value of T(3+) and T(4+)
      phenotype lymphocytes and elevation of number of T(8+)-lymphocytes were observed.
      On the background of normal values of B-lymphocytes appeared increase of IgM and
      decrease of IgG and IgA. In most cases significant elevation in the value of IgE 
      (244+10,3) and low values of INF-gamma, ultrastructural changes of blood
      monocytes were apparent. The peculiarities of ultrastructural changes of
      eosinophils and basophiles especially were pronounced by cytomembrane
      degranulation in form of decrease in electric density.

PMID- 16636389
TI  - [Risk factors of bronchial asthma in children].
AB  - Case representative selective study of children from 1 to 15 years old age in
      Batumi, with 2110 children population has been carried out. Risk factors were
      studied by interviewing method, using two step estimation (on the basis of
      primary and secondary questionnaire) of the disease developing risk. For
      statistical analysis of the data SPSS v. 12 was used. Study findings confirm
      causal connection (with high relative risk) and significant probability of the
      disease (with high attributive risk), with "major risk factors": allergic
      diseases and atopic dermatitis in relatives and with "minor risk factors":
      allergic rhinitis. Relatively weak risk factors (with low relative risk), but
      with high prevalence in child population in Batumi were found: respiratory
      infections and bottle-feeding. Revealing individual and population risk
      phenomenology of bronchial asthma in children population in Batumi, on the basis
      of that the most of risk factors can be monitored, will promote asthma prevention
      and population health care, which is more rational and cost-effective.

PMID- 16636390
TI  - [Interferon system and proinflammatory cytokine IL-1beta in frequently ill
      children during the remission period].
AB  - Investigation of cytokines IL-1beta, INF-alpha and INF-gamma in frequently ill
      children in the period of remission was the main objective of the study. Two
      groups of children were investigated: a) 8 preschool children aged 4-6; b) 20
      children aged 7-12. Interferon alpha and gamma were studied in the blood serum by
      Soloviov and Bektemirov method. IL-1beta was studied in the blood serum by hard
      phased immunoenzyme. Results were analysed by the computer program SPSS V 11.5.
      The patients were tested twice. During the first test indicators of interferon
      alpha and gamma were studied, and during the second test, performed within the 1
      2 years time period, indicators of IL -1beta were added. It was found that the
      level of IL -1beta (p<0,05) was elevated.

PMID- 16636391
TI  - [Predictive value of neurological evaluation of newborns].
AB  - The correct management of perinatal period, timely recognition and intervention
      of existing and prospective problems, definition of preventive measures gives us
      an opportunity to avoid and reduce all possible pathologic conditions,
      complications and their consequences. The goal of our investigation was the
      evaluation of neurological assessment of the pre-term and full-term newborn
      infants using Dubowitz scale and establishment of relations between obtained
      indices and neurodevelopmental outcome in children of this cohort. It was shown
      that Dubowitz neurological scale for infants gives an opportunity not only to
      separate the norm from pathology and detect particular problems of neonatal
      period, but also to determine contiguous conditions and define risk-factors. The
      results of our investigation coincide with reference data, which confirms that
      children of the risk-group more frequently have problems connected with the
      neurological development.

PMID- 16636392
TI  - [Maxipime in the treatment of neonatal sepsis].
AB  - The aim of our work was to confirm the effectiveness of the IV generation
      cephalosporin maxipime. Patients with sepsis, septicaemia (induced by
      enterobacter cloacae) were investigated. We utilized several antibiotics of large
      spectrum of action, but the situation was stabilized and improved after the
      initiation of maxipime. Stabilization of the intestinal peristaltic has been
      achieved using the nutritional mixture alfare (Nestle). Alfare totally satisfies
      child's demands on vitamins and microelements. Maxipime should be recommended to
      be included in the formulae of antibiotics at the pediatric intensive care units.
      Maxipime is the effective and safe antibiotic and has very good results in the
      cases of childhood sepsis with severe course, including septic shock and
      pollyorganic insufficiency.

PMID- 16636393
TI  - Vascularized flap prefabrication using rat caudal artery.
AB  - The experimental study was performed at the plastic and reconstructive surgery
      laboratory of the Georgian Medical Academy. The present study was designed to
      investigate the possibilities of neovascularization after rotation of
      arteriovenous pedicle from donor to recipient site (flap prefabrication). 70
      white Wister rats weighting 150 to 300 g were used in this study. The rats were
      divided in 2 groups: experimental (50) and control (20) groups. Arteriovenous
      vascularized flap formation was performed in the experimental group. Skeletonized
      caudal vascular pedicle was rotated to the rat back area and implanted underneath
      the subcutaneous pouch. The control group was divided into 2 groups: 1. The flap
      morphological study and 2. Skin tunneling and morphological study. At different
      time intervals after prefabrication (2 week, 1, 2, 3, 4, 6, 8, 10 month) the flap
      was morphologically studied and observed. Among the 2 control groups there were
      no difference according to the flap vascularization. In experimental group the
      results showed a progressive degree of neovascularization that correspond to the
      increasing length of the time that the pedicle was implanted in the flaps. In
      prefabricated flaps the number of newly formed vessels rather increased compared
      with control group, around the implanted artery and more around the implanted
      vein. The new vessels are of capillary type. There were no structural changes in
      the epidermis and dermis. It may be concluded that flap prefabrication is one of
      the real and alternative ways for tissue anatomical structure modelling.

PMID- 16636394
TI  - [Common intralobular microcirculatory module peculliarities in cholestasis in
      white rats].
AB  - The dynamics of intralobular microcirculatory module transformation in
      cholestasis was investigated. The liver tissues of 54 white Wistar rats were
      studied by Histology, TEM, TEM after injection of 1% Pb(NO(3))(3), vie common
      bile duct (CBD), SEM of corrosion casts prepared after methylmethacrylate
      injection vie CBD. It is demonstrated that liver is the basis of microcirculation
      of 4 different liquids: blood, bile, connective tissue liquid and lymph.
      Accordingly, in normal condition 4 different well formed compartments bordered
      from each-others by different types of cells exist. In the yearly stages of
      cholestasis (3-6 days) the function of bile drainage is partially overtaken by
      lymph pathways. This is accompanied by the beginning of the destruction of
      structures bordering above-mentioned microcirculatory beds. In the later stages
      of cholestasis (12-18 days) the final disorganization of microcirculatory
      compartments with mixture of all liquids is observed. It is accompanied by
      increased dystrophy of liver cells population.

PMID- 16636395
TI  - Toxic acute liver failure treatment by isolated hepatocytes allotransplantation
      in experimental.
AB  - Acute liver failure treatment nowadays is a common problem in modern hepatology,
      despite of well studied pathogenesis and treatment modalities, lethality of the
      disease is still high, and in 21 century in the world's best clinics it accounts
      to 70-80%. For uptake of isolated hepatocytes we uses the fermental-mechanical
      method modified by Korukhov (1983) for the treatment of acute liver failure by
      hepatocyte allotransplantation and to stimulate liver reparative regeneration
      processes, which gives a chance to liver for the function restoration by
      replacement of injured hepatocytes with transplanted liver cells. We provide
      experiments on 45 white laboratory Vistar line rats (150-200gr) which were kept
      on standard environment, animals were divided into three equal groups: I group
      (n=20) was served as a control group, in which we provide acute liver failure
      modelling, by toxic agent (carbontetrachloride CCL4 ) treatment by naso-gastric
      tube, After acute liver failure modelling, in the II group (n=20) of animals we
      were conducting liver cell transplantation, III group (n=5) animals were served
      as donors for isolated hepatocyte uptake. Cell ultrastructure element
      proliferation clearly seen by morphological evaluation and animals which have
      acute liver failure had a chance for survival and it may be concluded that our
      proposed method can be the curative treatment method of acute liver failure in
      experiment.

PMID- 16636396
TI  - [Ultrastructural peculiarities of heart of rats of various ages at different
      levels of antigen load].
AB  - The aim of the research was to investigate electron-microscopic peculiarities of
      heart at different levels of antigen loading using adult and old aged gnotobiont
      rats, conventional rats and rats with experimental autoimmune cardiomyopathy. The
      results of investigations showed that the ultrasrtuctural characteristics of
      heart greatly depend on microbiological status and age of experimental animals.
      The ultrasrtucture of heart of adult rats mostly depend on the level of intensity
      of antigen loading. In all experimental groups of old rats the subcellular
      differences had the same directions. Although, it must be mentioned that there
      was not significant correlation between the level of heart damage and intensity
      of antigen loading. According to this, age-related changes depend not only on
      microbiological status of organism, but on genetically determined peculiarities
      of internal regulative processes taking place during the ontogenesis. Thus, the
      received results may be used to identify age-related changes, which give us the
      possibility for the differentiation between age-related and pathological
      peculiarities.

PMID- 16636397
TI  - [Assessment of the lower threshold in autoregulation of the blood supply of the
      optic nerve disk].
AB  - Existence of the autoregulation phenomenon in the blood supply system of the
      optic nerve has been established in the 1990; however, some of its quantitative
      and qualitative characteristics still require clarification. The goal of the
      present work was assessment of the lower margin in autoregulation of the blood
      supply of the optic nerve in the rabbit in conditions of attenuated level of
      perfusion pressure. Total of six adult rabbits weighing 2.5-3.0 kg, anesthetized
      with urethane (0.9-1.1 g/kg) were investigated in acute experiments. Intensity of
      the local blood flow in the optic nerve disk was evaluated quantitatively by
      means of the hydrogen clearance. The frontal chamber of an eye was punctured with
      syringe needle, which via silicon tube was attached to the reservoir filled with
      artificial aqueous humor. Adjustment of vertical position of the reservoir
      provided different levels of the intraocular pressure. Calculation of the
      perfusion pressure of the eye was made according to mean level of the systemic
      arterial pressure, intraocular pressure, and a constant, which depends on an
      animal species. The results obtained allow suggesting with a certain degree of
      precision that elevation of the intraocular pressure to about 40-50 mmHg does not
      alter the blood supply of the optic nerve disk. Its further increase however
      leads to almost linear dependence between elevation of the intraocular pressure
      and decrease of the blood supply of the optic nerve disk. Meanwhile, the systemic
      arterial pressure should be considered as well, because volume of the perfusion
      pressure in the eye is determined by difference between systemic arterial- and
      intraocular pressures.

PMID- 16636398
TI  - [Experimental support for the application of plasma streams in the treatment of
      gunshot wounds of extremities].
AB  - Experimental data on the application of plasma streams (PS) for the treatment of
      gunshot wounds of extremities is presented. On the basis of the investigated
      material (20 animals in which treatment included PS compared to 10 animals where
      treatment was carried out without SP application) it was established, that bullet
      wounds of extremities are cleared of pathogenic microflora in shorter terms, the
      expressed anesthetizing effect was observed, basic function of finiteness was
      restored 4 - 5 days earlier. The common reduction of time parameters was in
      average 22 - 25%. By all parameters results of the treatment in the group with PS
      application were much better, especially by such criteria, as frequency of
      purulent complications in the early postoperative period and reliability of the
      hemostasis. The opportunity of application of PS is authentically proved at
      operations on extremities, including those with the damage of bone structures,
      nervous trunks, at amputations, at purulent complications, i.e. practically at
      all possible variants of the damage of extremities and their consequences.

PMID- 16636399
TI  - [Biochemical, pharmacological and clinical aspects of influencing methioninc,
      tryptophan, pyridoxine (vitamin B6), Ca2+ and high-calorie food on the synthesis
      and intensity of the secretion of melatonin].
AB  - The goal of the investigation was the determination of the influence of Ca(2+),
      vitamin B6 methionine, tryptophan, the combination of the listed elements and
      high-calorie food on the intensity of synthesis and secretion of melatonin. The
      level of melatonin in the blood serum was being determined through the method of
      radio-immune (immune-enzyme) analysis. Based on the results received it was found
      out that the influence of the vitamin B6, tryptophan and their combination in the
      organism of the tested objects - white rats) resulted in the considerable
      increase of formation of melatonin. In the conditions of feeding them with high
      calorie food - the value of melatonin in blood is sharply reducing. Consequently
      we may conclude that the vitamin B6 and tryptophan separately and in combination,
      either directly or through some other mechanism participate actively in
      biosynthesis and secretion of melatonin. The high-calorie food through unknown
      mechanism to us reduces the formation of the melatonin in epiphysis. This might
      point to the important role of the deficit of melatonin in etiopathogenesis of
      the diseases, detected and developed on the background of hypercholesterinemy.

PMID- 16636400
TI  - [Oxidative stress during thyrotoxicosis and its correction].
AB  - Oligocrine is a preparation of vegetable origin characterized by anti
      inflammatory, antioxidant, immunomodulating properties. Our study shows that
      administration of L-thyroxine injections (irrespective of the duration) results
      in elevated synthesis of thyroid hormones and intensification of oxidative stress
      in experimental animals. These changes are evidenced by accumulation of membrane
      phospholipide peroxidation products - lipid peroxides in the blood. At that we
      should point that while dependence of FT3 and FT4 levels on the duration of L
      thyroxine administration was insignificant in the experimental model of
      thyrotoxicosis, intensity of lipid peroxidation increased along with prolongation
      of injections. Blood levels of free nitric oxide were decreased likely due to the
      transformation of nitric oxide into peroxinitrite. Oligocrine facilitates to the
      stabilization of thyroid status and restriction of NO hyperproduction,
      hypermetabolism and oxidative stress in the body.

PMID- 16636401
TI  - A 3D reconstruction algorithm for EIT using a handheld probe for breast cancer
      detection.
AB  - A 3D reconstruction algorithm for electrical impedance tomography is presented
      for determining the distribution of electrical properties inside the body, given
      electrical measurements made on the surface. A linearized reconstruction
      algorithm using planar electrode arrays in a handheld probe geometry developed by
      Mueller et al (1999 IEEE Trans. Biomed. Eng. 46 1379-86) has been refined and
      extended in this paper. This algorithm is based on linearizing the conductivity
      about a constant value. We have extended the distance below the electrodes at
      which a target can be imaged by using a combination of two regularization schemes
      and a weighted mesh. An appropriate combination of Tikhonov and NOSER
      regularization produces satisfactory static images of a 2 cm cube placed 2 cm
      below the array, and difference images of a 1 cm cube 4 cm away from the array.
      The weighted mesh allows use of fixed regularization parameters for all depths of
      the target.

PMID- 16636402
TI  - Imaging of conductivity changes and electrode movement in EIT.
AB  - Electrical impedance tomography (EIT) attempts to reconstruct the internal
      impedance distribution in a medium from electrical measurements at electrodes on
      the medium surface. One key difficulty with EIT measurements is due to the
      position uncertainty of the electrodes, especially for medical applications, in
      which the body surface moves during breathing and posture change. In this paper,
      we develop a new approach which directly reconstructs both electrode movements
      and internal conductivity changes for difference EIT. The reconstruction problem
      is formulated in terms of a regularized inverse, using an augmented Jacobian,
      sensitive to impedance change and electrode movement. A reconstruction prior term
      is computed to impose a smoothness constraint on both the spatial distribution of
      impedance change and electrode movement. A one-step regularized imaging algorithm
      is then implemented based on the augmented Jacobian and smoothness constraint.
      Images were reconstructed using the algorithm of this paper with data from
      simulated 2D and 3D conductivity changes and electrode movements, and from saline
      phantom measurements. Results showed good reconstruction of the actual electrode
      movements, as well as a dramatic reduction in image artefacts compared to images
      from the standard algorithm, which did not account for electrode movement.

PMID- 16636403
TI  - Comparison of different methods to define regions of interest for evaluation of
      regional lung ventilation by EIT.
AB  - The measurement of regional lung ventilation by electrical impedance tomography
      (EIT) has been evaluated in many experimental studies. However, EIT is not
      routinely used in a clinical setting, which is attributable to the fact that a
      convenient concept for how to quantify the EIT data is missing. The definition of
      region of interest (ROI) is an essential point in the data analysis. To date,
      there are only limited data available on the different approaches to ROI
      definition to evaluate regional lung ventilation by EIT. For this survey we
      examined ten patients (mean age +/- SD: 60 +/- 10 years) under controlled
      ventilation. Regional tidal volumes were quantified as pixel values of
      inspiratory-to-expiratory impedance differences and four types of ROIs were
      subsequently applied. The definition of ROI contours was based on the calculation
      of the pixel values of (1) standard deviation from each pixel set of impedance
      data and (2) the regression coefficient from linear regression equations between
      the individual local (pixel) and average (whole scan) impedance signals.
      Additionally, arbitrary ROIs (four quadrants and four anteroposterior segments of
      equal height) were used. Our results indicate that both approaches to ROI
      definition using statistical parameters are suitable when impedance signals with
      high sensitivity to ventilation-related phenomena are to be analyzed. The
      definition of the ROI contour as 20-35% of the maximum standard deviation or
      regression coefficient is recommended. Simple segmental ROIs are less convenient
      because of the low ventilation-related signal component in the dorsal region.

PMID- 16636404
TI  - Study of the optimum level of electrode placement for the evaluation of absolute
      lung resistivity with the Mk3.5 EIT system.
AB  - Inter-subject variability has caused the majority of previous electrical
      impedance tomography (EIT) techniques to focus on the derivation of relative or
      difference measures of in vivo tissue resistivity. Implicit in these techniques
      is the requirement for a reference or previously defined data set. This study
      assesses the accuracy and optimum electrode placement strategy for a recently
      developed method which estimates an absolute value of organ resistivity without
      recourse to a reference data set. Since this measurement of tissue resistivity is
      absolute, in Ohm metres, it should be possible to use EIT measurements for the
      objective diagnosis of lung diseases such as pulmonary oedema and emphysema.
      However, the stability and reproducibility of the method have not yet been
      investigated fully. To investigate these problems, this study used a Sheffield
      Mk3.5 system which was configured to operate with eight measurement electrodes.
      As a result of this study, the absolute resistivity measurement was found to be
      insensitive to the electrode level between 4 and 5 cm above the xiphoid process.
      The level of the electrode plane was varied between 2 cm and 7 cm above the
      xiphoid process. Absolute lung resistivity in 18 normal subjects (age 22.6 +/-
      4.9, height 169.1 +/- 5.7 cm, weight 60.6 +/- 4.5 kg, body mass index 21.2 +/-
      1.6: mean +/- standard deviation) was measured during both normal and deep
      breathing for 1 min. Three sets of measurements were made over a period of
      several days on each of nine of the normal male subjects. No significant
      differences in absolute lung resistivity were found, either during normal tidal
      breathing between the electrode levels of 4 and 5 cm (9.3 +/- 2.4 Omega m, 9.6 +/
      1.9 Omega m at 4 and 5 cm, respectively: mean +/- standard deviation) or during
      deep breathing between the electrode levels of 4 and 5 cm (10.9 +/- 2.9 Omega m
      and 11.1 +/- 2.3 Omega m, respectively: mean +/- standard deviation). However,
      the differences in absolute lung resistivity between normal and deep tidal
      breathing at the same electrode level are significant. No significant difference
      was found in the coefficient of variation between the electrode levels of 4 and 5
      cm (9.5 +/- 3.6%, 8.5 +/- 3.2% at 4 and 5 cm, respectively: mean +/- standard
      deviation in individual subjects). Therefore, the electrode levels of 4 and 5 cm
      above the xiphoid process showed reasonable reliability in the measurement of
      absolute lung resistivity both among individuals and over time.

PMID- 16636405
TI  - Reducing boundary effects in static EIT imaging.
AB  - Electrical impedance tomography (EIT) is a non-invasive technique used to image
      the electrical conductivity and permittivity within a body from measurements
      taken on the body's surface. High-quality static images are required for many
      medical imaging applications. Forming such images usually requires an accurate
      way to calculate the expected voltages on the surface resulting from the
      application of known currents to that surface. This is described as the forward
      problem. This paper introduces a new method to improve static images by using an
      improved forward solution which estimates a different conductivity value for each
      applied current pattern. This method, creating an automatically adjusting forward
      solution, can improve the sensitivity of static images under many EIT imaging
      applications. It does so by reducing the boundary effects caused by electrodes
      and any layered structures near them such as skin. The drawback of this method is
      that circularly symmetric structures of interest may be suppressed or eliminated
      from the images. The performance of this method is illustrated in a 2D circular
      phantom with simulation data from both a FEM model and experimental data.

PMID- 16636406
TI  - Parametric EIT for monitoring cardiac stroke volume.
AB  - The bio-impedance technique appears appropriate for non-invasive cardiac stroke
      volume (SV) measurement, as the thoracic conductivity distribution is altered
      during the cardiac cycle due to the heart contraction and blood perfusion. In the
      present work, the feasibility of a parametric electrical impedance tomography
      (EIT) for assessing the cardiac SV was studied. An impedance model of the thorax
      was constructed from segmented axial MRI images along 19 phases of the cardiac
      cycle. The heart was simulated as an ellipsoid, with its axes' lengths set as the
      reconstruction parameters, while all other tissues' geometry and conductivity
      values were kept fixed. A Newton-Raphson parametric optimization scheme was
      utilized, yielding a correlation between the reconstructed and anatomical left
      ventricular volumes of 0.97 (p = 2 x 10(-11)). An analysis of noise sensitivity
      showed that the proposed algorithm requires an SNR greater than 65 dB. The
      simulation results were compared to physical data, collected with a portable EIT
      system (PulmoTrace, CardioInspect). The validation study was employed for a group
      of N = 28 healthy patients, and a comparison with impedance cardiography
      measurements (BioZ, Cardiodynamics) was made, showing a correlation of r = 0.86
      (p = 4 x10(-9)). The preliminary results demonstrate that parametric EIT has the
      potential to measure SV, and may be applicable for both clinical and home
      environment usage.

PMID- 16636407
TI  - Multi-frequency electrical impedance tomography (EIT) of the adult human head:
      initial findings in brain tumours, arteriovenous malformations and chronic
      stroke, development of an analysis method and calibration.
AB  - MFEIT (multi-frequency electrical impedance tomography) could distinguish between
      ischaemic and haemorrhagic stroke and permit the urgent use of thrombolytic drugs
      in patients with ischaemic stroke. The purpose of this study was to characterize
      the UCLH Mk 2 MFEIT system, designed for this purpose, with 32 electrodes and a
      multiplexed 2 kHz to 1.6 MHz single impedance measuring circuit. Data were
      collected in seven subjects with brain tumours, arteriovenous malformations or
      chronic stroke, as these resembled the changes in haemorrhagic or ischaemic
      stroke. Calibration studies indicated that the reliable bandwidth was only 16-64
      kHz because of front-end components placed to permit simultaneous EEG recording.
      In raw in-phase component data, the SD of 16-64 kHz data for one electrode
      combination across subjects was 2.45 +/- 0.9%, compared to a largest predicted
      change of 0.35% estimated using the FEM of the head. Using newly developed
      methods of examining the most sensitive channels from the FEM, and nonlinear
      imaging constrained to the known site of the lesion, no reproducible changes
      between pathologies were observed. This study has identified a specification for
      accuracy in EITS in acute stroke, identified the size of variability in relation
      to this in human recordings, and presents new methods for analysis of data.
      Although no reproducible changes were identified, we hope this will provide a
      foundation for future studies in this demanding but potentially powerful novel
      application.

PMID- 16636408
TI  - Factors limiting the application of electrical impedance tomography for
      identification of regional conductivity changes using scalp electrodes during
      epileptic seizures in humans.
AB  - Electrical impedance tomography (EIT) has the potential to produce images during
      epileptic seizures. This might improve the accuracy of the localization of
      epileptic foci in patients undergoing presurgical assessment for curative
      neurosurgery. It has already been shown that impedance increases by up to 22%
      during induced epileptic seizures in animal models, using cortical or implanted
      electrodes in controlled experiments. The purpose of this study was to determine
      if reproducible raw impedance changes and EIT images could be collected during
      epileptic seizures in patients who were undergoing observation with video
      electroencephalography (EEG) telemetry as part of evaluation prior to
      neurosurgery to resect the region of brain causing the epilepsy. A secondary
      purpose was to develop an objective method for processing and evaluating data, as
      seizures arose at unpredictable times from a noisy baseline. Four-terminal
      impedance measurements from 258 combinations were collected continuously using 32
      EEG scalp electrodes in 22 seizure episodes from 7 patients during their
      presurgical assessment together with the standard EEG recordings. A reliable
      method for defining the pre-seizure baseline and recording impedance data and EIT
      images was developed, in which EIT and EEG could be acquired simultaneously after
      filtering of EIT artefact from the EEG signal. Fluctuations of several per cent
      over minutes were observed in the baseline between seizures. During seizures,
      boundary voltage changes diverged with a standard deviation of 1-54% from the
      baseline. No reproducible changes with the expected time course of some tens of
      seconds and magnitude of about 0.1% could be reliably measured. This demonstrates
      that it is feasible to acquire EIT images in parallel with standard EEG during
      presurgical assessment but, unfortunately, expected EIT changes on the scalp of
      about 0.1% are swamped by much larger movement and systematic artefact.
      Nevertheless, EIT has the unique potential to provide invaluable neuroimaging
      data for this purpose and may still become possible with improvements in
      electrode design and instrumentation.

PMID- 16636409
TI  - Detecting cryoablation with EIT and the benefit of including ice front imaging
      data.
AB  - Imaging has made cryosurgery, the destruction of unwanted tissue through
      freezing, valuable. Electrical impedance tomography (EIT) has been explored as a
      method to determine the volume of tissue that is frozen during the procedure.
      However, studies have shown that tissue near the edge of the frozen zone often
      survives since in this region it may only be the extra-cellular space that is
      frozen. This threatens the usefulness of cryosurgery for cancer therapy since
      inaccurate ablation either allows the cancer to survive or increases the chances
      of complications. Since low-frequency conductivity of tissue increases due to
      cell membrane impairment, and ablated tissue implies impaired membranes, EIT has
      the capability to recover images of tissue viability. Cryosurgery is a technique
      that can benefit from this: EIT scans before freezing and after thawing can show
      changes in conductivity and hence viability due to treatment. Assuming unfrozen
      tissue will survive treatment, we explore the use of differential EIT in
      combination with intra-operative ice front imaging modes that are currently in
      clinical practice to recover enhanced-resolution images of cryosurgical treatment
      efficacy in a set of simulated experiments. We also investigate the sensitivity
      to violation of this assumption and predict tolerable levels of measurement
      noise.

PMID- 16636410
TI  - Imaging pathologic pulmonary air and fluid accumulation by functional and
      absolute EIT.
AB  - The increasing use of EIT in clinical research on severely ill lung patients
      requires a clarification of the influence of pathologic impedance distributions
      on the validity of the resulting tomograms. Significant accumulation of low
      conducting air (e.g. pneumothorax or emphysema) or well-conducting liquid (e.g.
      haematothorax or atelectases) may conflict with treating the imaging problem as
      purely linear. First, we investigated the influence of stepwise inflation and
      deflation by up to 300 ml of air and 300 ml of Ringer solution into the pleural
      space of five pigs on the resulting tomograms during ventilation at constant
      tidal volume. Series of EIT images representing relative impedance changes were
      generated on the basis of a modified Sheffield back projection algorithm and
      ventilation distribution was displayed as functional (f-EIT) tomograms. In
      addition, a modified simultaneous iterative reconstruction technique (SIRT) was
      applied to quantify the resistivity distribution on an absolute level scaled in
      Omega m (a-EIT). Second, we applied these two EIT techniques on four intensive
      care patients with inhomogeneous air and fluid distribution and compared the EIT
      results to computed tomography (CT) and to a reference set of intrathoracic
      resistivity data of 20 healthy volunteers calculated by SIRT. The results of the
      animal model show that f-EIT based on back projection is not disturbed by the
      artificial pneumo- or haematothorax. Application of SIRT allows reliable
      discrimination and detection of the location and amplitude of pneumo- or
      haematothorax. These results were supported by the good agreement between the
      electrical impedance tomograms and CT scans on patients and by the significant
      differences of regional resistivity data between patients and healthy volunteers.

PMID- 16636411
TI  - Design and calibration of a compact multi-frequency EIT system for acute stroke
      imaging.
AB  - A new, compact UCLH Mk 2.5 EIT system has been developed and calibrated for EIT
      imaging of the head. Improvements include increased input and output impedances,
      increased bandwidth and improved CMRR (80 dB) and linearity over frequencies and
      load (0.2% on a single channel, +/-0.7% on a saline tank over 20 Hz-256 kHz and
      10-65 Omega). The accuracy of the system is sufficient to image severe acute
      stroke according to the specification from recent detailed anatomical modelling
      (Horesh et al 2005 3rd European Medical and Biological Engineering Conference
      EMBEC'05). A preliminary human study has validated the main specifications of the
      modelling, the range of trans-impedance from the head (8-70 Omega) using a 32
      electrode, 258 combination protocol and contact impedances of 300 Omega to 2.7
      kOmega over 20 Hz to 256 kHz.

PMID- 16636412
TI  - Identification of a suitable current waveform for acute stroke imaging.
AB  - MFEIT (multi-frequency electrical impedance tomography) has the potential to
      provide a portable non-invasive neuroimaging method ideal for use in acute
      stroke. Skin perception has not previously occurred in MFEIT with injected
      frequencies above 2 kHz, but use in brain imaging requires applied current below
      100 Hz, which could stimulate cutaneous nerve endings. The purpose of this work
      was to find the most suitable current pattern that could be employed in MFEIT
      measurements in the adult head with the UCLH Mk2.5 system, which applies currents
      from 20 Hz-1.6 MHz. Single frequency current waveforms of 0.28 mA peak-to-peak at
      20 Hz-80 Hz were applied to the forearms of three volunteers; although the skin
      was abraded, none of these were perceived, which agrees with similar studies in
      the literature. When a full frequency pattern at 20 Hz-1.6 MHz was applied to the
      forearm or head in four healthy subjects, with the same current amplitude of 0.28
      mA for each component, an unpleasant tingling sensation was perceived, due to
      summation of the applied currents. The sensation was reduced or abolished by
      attenuation or removal of frequencies below 100 Hz; the optimal compromise was a
      pattern with absence of 40 Hz, and with 80 and 20 Hz respectively reduced to 75%
      and 50%.

PMID- 16636413
TI  - A high-precision voltage source for EIT.
AB  - Electrical impedance tomography (EIT) utilizes electrodes placed on the surface
      of a body to determine the complex conductivity distribution within the body. EIT
      can be performed by applying currents through the electrodes and measuring the
      electrode voltages or by applying electrode voltages and measuring the currents.
      Techniques have also been developed for applying the desired currents using
      voltage sources. This paper describes a voltage source for use in applied-voltage
      EIT that includes the capability of measuring both the applied voltage and
      applied current. A calibration circuit and calibration algorithm are described
      which enables all voltage sources in an EIT system to be calibrated to a common
      standard. The calibration minimizes the impact of stray shunt impedance, passive
      component variability and active component non-ideality. Simulation data obtained
      using PSpice are used to demonstrate the effectiveness of the circuits and
      calibration algorithm.

PMID- 16636414
TI  - Reconstruction of the shape of conductivity spectra using differential multi
      frequency magnetic induction tomography.
AB  - Magnetic induction tomography (MIT) of biological tissue is used for the
      reconstruction of the complex conductivity distribution kappa inside the object
      under investigation. It is based on the perturbation of an alternating magnetic
      field caused by the object and can be used in all applications of electrical
      impedance tomography (EIT) such as functional lung monitoring and assessment of
      tissue fluids. In contrast to EIT, MIT does not require electrodes and magnetic
      fields can also penetrate non-conducting barriers such as the skull. As in EIT,
      the reconstruction of absolute conductivity values is very difficult because of
      the method's sensitivity to numerical errors and noise. To overcome this problem,
      image reconstruction in EIT is often done differentially. Analogously, this
      concept has been adopted for MIT. Two different methods for differential imaging
      are applicable. The first one is state-differential, for example when the
      conductivity change between inspiration and expiration in the lung regions is
      being detected. The second one is frequency-differential, which is of high
      interest in motionless organs like the brain, where a state-differential method
      cannot be applied. An equation for frequency-differential MIT was derived taking
      into consideration the frequency dependence of the sensitivity matrix. This
      formula is valid if we can assume that only small conductivity changes occur. In
      this way, the non-linear inverse problem of MIT can be approximated by a linear
      one (depending only on the frequency), similar to in EIT. Keeping this limitation
      in mind, the conductivity changes between one or more reference frequencies and
      several measurement frequencies were reconstructed, yielding normalized
      conductivity spectra. Due to the differential character of the method, these
      spectra do not provide absolute conductivities but preserve the shape of the
      spectrum. The validity of the method was tested with artificial data generated
      with a spherical perturbation within a conducting cylinder as well as for real
      measurement data. The measurement data were obtained from a potato immersed in
      saline. The resulting spectra were compared with reference measurements and the
      preservation of the shape of the spectra was analyzed.

PMID- 16636415
TI  - Solution of the inverse problem of magnetic induction tomography (MIT) with
      multiple objects: analysis of detectability and statistical properties with
      respect to the reconstructed conducting region.
AB  - Magnetic induction tomography (MIT) is a technique to image the passive
      electrical properties (i.e. conductivity, permittivity, permeability) of
      biological tissues. The inverse eddy current problem is nonlinear and ill-posed,
      thus a Gauss-Newton one-step method in combination with four different
      regularization schemes is used to obtain stable solutions. Simulations with 16
      excitation coils, 32 receiving coils and different spherical perturbations inside
      a homogeneous cylinder were computed. In order to compare the statistical
      properties of the reconstructed results a Monte Carlo study with a SNR of 40 dB
      and 20 dB was carried out. Simulated conductivity perturbations inside a
      homogeneous cylinder can be localized and resolved and the results prove the
      feasibility of difference imaging with MIT.

PMID- 16636416
TI  - Uses and abuses of EIDORS: an extensible software base for EIT.
AB  - EIDORS is an open source software suite for image reconstruction in electrical
      impedance tomography and diffuse optical tomography, designed to facilitate
      collaboration, testing and new research in these fields. This paper describes
      recent work to redesign the software structure in order to simplify its use and
      provide a uniform interface, permitting easier modification and customization. We
      describe the key features of this software, followed by examples of its use. One
      general issue with inverse problem software is the difficulty of correctly
      implementing algorithms and the consequent ease with which subtle numerical bugs
      can be inadvertently introduced. EIDORS helps with this issue, by allowing
      sharing and reuse of well-documented and debugged software. On the other hand,
      since EIDORS is designed to facilitate use by non-specialists, its use may
      inadvertently result in such numerical errors. In order to address this issue, we
      develop a list of ways in which such errors with inverse problems (which we refer
      to as 'cheats') may occur. Our hope is that such an overview may assist authors
      of software to avoid such implementation issues.

PMID- 16636417
TI  - High field MREIT: setup and tissue phantom imaging at 11 T.
AB  - Magnetic resonance electrical impedance tomography (MREIT) has the potential to
      provide conductivity and current density images with high spatial resolution and
      accuracy. Recent experimental studies at a field strength of 3 T showed that the
      spatial resolution of conductivity and current density images may be similar to
      that of conventional MR images as long as enough current is injected, at least 20
      mA when the object being imaged has a size similar to the human head. To apply
      the MREIT technique to image small conductivity changes using less injection
      current, we performed MREIT studies at 11 T field strength, where noise levels in
      measured magnetic flux density data are significantly lower. In this paper we
      present the experimental results of imaging biological tissues with different
      conductivity values using MREIT at 11 T. We describe technical difficulties
      encountered in using high-field MREIT systems and possible solutions. High-field
      MREIT is suggested as a research tool for obtaining accurate conductivity data
      from tissue samples and animal subjects.

PMID- 16636418
TI  - A multifrequency magnetic induction tomography system using planar gradiometers:
      data collection and calibration.
AB  - We developed a 14-channel multifrequency magnetic induction tomography system (MF
      MIT) for biomedical applications. The excitation field is produced by a single
      coil and 14 planar gradiometers are used for signal detection. The object under
      measurement was rotated (16 steps per turn) to obtain a full data set for image
      reconstruction. We make measurements at frequencies from 50 kHz to 1 MHz using a
      single frequency excitation signal or a multifrequency signal containing several
      frequencies in this range. We used two acquisition boards giving a total of eight
      synchronous channels at a sample rate of 5 MS s(-1) per channel. The real and
      imaginary parts of DeltaB/B(0) were calculated using coherent demodulation at all
      injected frequencies. Calibration, averaging and drift cancellation techniques
      were used before image reconstruction. A plastic tank filled with saline (D = 19
      cm) and with conductive and/or paramagnetic perturbations was measured for
      calibration and test purposes. We used a FEM model and an eddy current solver to
      evaluate the experimental results and to reconstruct the images. Measured
      equivalent input noise voltage for each channel was 2 nV Hz(-1/2). Using coherent
      demodulation, with an integration time of 20 ms, the measured STD for the
      magnitude was 7 nV(rms) (close to the theoretical value only taking into account
      the amplifier's thermal noise). For long acquisition times the drift in the
      signal produced a bigger effect than the input noise (typical STD was 10 nV with
      a maximum of 35 nV at one channel) but this effect was reduced using a drift
      cancellation technique based on averaging. We were able to image a 2 S m(-1) agar
      sphere (D = 4 cm) inside the tank filled with saline of 1 S m(-1).

PMID- 16636419
TI  - Imaging cardiac activity by the D-bar method for electrical impedance tomography.
AB  - A practical D-bar algorithm for reconstructing conductivity changes from EIT data
      taken on electrodes in a 2D geometry is described. The algorithm is based on the
      global uniqueness proof of Nachman (1996 Ann. Math. 143 71-96) for the 2D inverse
      conductivity problem. Results are shown for reconstructions from data collected
      on electrodes placed around the circumference of a human chest to reconstruct a
      2D cross-section of the torso. The images show changes in conductivity during a
      cardiac cycle.

PMID- 16636420
TI  - A method for modelling and optimizing an electrical impedance tomography system.
AB  - Electrical impedance tomography (EIT) image reconstruction is an ill-posed
      problem requiring maximum measurement precision. Recent EIT systems claim 60 to
      80 dB precision. Achieving higher values is hard in practice since measurements
      must be performed at relatively high frequency, on a living subject, while using
      components whose tolerance is usually higher than 0.1%. To circumvent this
      difficulty, a method for modelling the electronic circuits of an EIT system was
      developed in order to optimize the circuits and incorporate the model in the
      reconstruction algorithms. The proposed approach is based on a matrix method for
      solving electrical circuits and has been applied to the scan-head which contains
      the front-end electronic circuits of our system. The method is used to simulate
      the system characteristic curves which are then optimized with the Levenberg
      Marquardt method to find optimal component values. A scan-head was built with the
      new component values and its simulated performance curves were compared with
      network analyser measurements. As a result of the optimization, the impedance at
      the operating frequency was increased to minimize the effects of variations in
      skin/electrode contact impedance. The transconductance and gain frequency
      responses were also reshaped to reduce noise sensitivity and unintended signal
      modulation. Integrating the model in the reconstruction algorithms should further
      improve overall performance of an EIT system.

PMID- 16636421
TI  - Objective selection of hyperparameter for EIT.
AB  - An algorithm for objectively calculating the hyperparameter for linearized one
      step electrical impedance tomography (EIT) image reconstruction algorithms is
      proposed and compared to existing strategies. EIT is an ill-conditioned problem
      in which regularization is used to calculate a stable and accurate solution by
      incorporating some form of prior knowledge into the solution. A hyperparameter is
      used to control the trade-off between conformance to data and conformance to the
      prior. A remaining challenge is to develop and validate methods of objectively
      selecting the hyperparameter. In this paper, we evaluate and compare five
      different strategies for hyperparameter selection. We propose a calibration-based
      method of objective hyperparameter selection, called BestRes, that leads to
      repeatable and stable image reconstructions that are indistinguishable from
      heuristic selections. Results indicate: (1) heuristic selections of
      hyperparameter are inconsistent among experts, (2) generalized cross-validation
      approaches produce under-regularized solutions, (3) L-curve approaches are
      unreliable for EIT and (4) BestRes produces good solutions comparable to expert
      selections. Additionally, we show that it is possible to reliably detect an
      inverse crime based on analysis of these parameters.

PMID- 16636422
TI  - Dynamic electrical impedance imaging of a chest phantom using the Kalman filter.
AB  - A dynamic complex impedance imaging technique is developed with the aid of the
      linearized Kalman filter (LKF) for real-time reconstruction of the human chest.
      The forward problem is solved by an analytical method based on the separation of
      variables and Fourier series. The inverse problem is treated as a state
      estimation problem. The nonlinear measurement equation is linearized about the
      best homogeneous impedivity value as an initial guess, and the impedivity
      distribution is estimated with the aid of the Kalman estimator. The Kalman gain
      matrix is pre-computed and stored off-line to minimize the on-line computational
      time. Simulation and phantom experiment are reported to illustrate the
      reconstruction performances in the sense of spatio-temporal resolution in a
      simplified geometry of the human chest.

PMID- 16636423
TI  - Direct reconstruction of tissue parameters from differential multifrequency EIT
      in vivo.
AB  - The basic purpose of electrical impedance tomography (EIT) is the reconstruction
      of conductivity distributions. While multifrequency measurements are of common
      use, the majority of reconstructed images are still conductivity distributions
      from one single frequency. More interesting than conductivities at each frequency
      are electrical tissue parameters, which describe the frequency-dependent
      conductivity changes of tissue. These parameters give information about
      physiological or electrical properties of tissues. By using this spectral
      information, a classification of different tissue types is possible. To get a
      distribution of tissue parameters, usually a posterior fitting of a tissue model
      to the conductivity spectra obtained with classical reconstruction algorithms at
      various frequencies is used. In this work, a single-step reconstruction algorithm
      for differential imaging was developed for the direct estimation of Cole
      parameters. This method is termed differential parametric reconstruction. The
      Cole model was used as the underlying tissue model, where only the relative
      changes of the two conductivity parameters sigma(0) and sigma(infinity) were
      reconstructed and the other two parameters of the model which are less
      identifiable were set to constant values. The reconstruction algorithm was tested
      with simulated noisy datasets and real measurement data from EIT measurements on
      the human thorax. These measurements were taken from healthy subjects and from
      patients with a serious lung injury. The new method yields a good image quality
      and higher robustness against noise compared to conventional reconstruction
      methods.

PMID- 16636424
TI  - A new non-surgical approach for treatment of extreme dolichocephalic
      malocclusions. Part 1. Appliance design and mechanotherapy.

PMID- 16636425
TI  - Incisor intrusion with Invisalign treatment of an adult periodontal patient.

PMID- 16636426
TI  - A quick and inexpensive means of treating mild lower anterior spacing.

PMID- 16636427
TI  - What's with the long face?

PMID- 16636428
TI  - A simplified means of engaging the Outrigger appliance.

PMID- 16636429
TI  - Clinical comparison of bond failures using different enamel preparations of
      severely fluorotic teeth.

PMID- 16636430
TI  - The readers' corner. On what percentage of your patients do you perform enamel
      reproximation?

PMID- 16636431
TI  - The readers' corner. Have you employed one or more practice management
      consultants?

PMID- 16636432
TI  - Mandibular distraction osteogenesis with a new ratchet screw.

PMID- 16636433
TI  - A new non-surgical approach for treatment of extreme dolichocephalic
      malocclusions. Part 2. Case selection and management.

PMID- 16636435
TI  - Our evolving standards.

PMID- 16636434
TI  - Biomechanics of skeletal anchorage. Part 1. Class II extraction treatment.

PMID- 16636436
TI  - Temporary bite-raising crowns.

PMID- 16636437
TI  - Setting employee compensation.

PMID- 16636438
TI  - The case for ownership.

PMID- 16636439
TI  - Construction and characterization of nisin-controlled expression vectors for use
      in Lactobacillus reuteri.
AB  - The Nisin-controlled gene expression (NICE) system, which was discovered in
      Lactococcus lactis, was adapted to Lactobacillus reuteri by ligating nisA
      promoter (PnisA) and nisRK DNA fragments into the Escherichia coli-Lb. reuteri
      shuttle vector pSTE32. This chimerical plasmid (pNICE) was capable of expressing
      the heterologous amylase gene (amyL) under nisin induction. Optimization of
      induction factors for this Lb. reuteri/pNICE system, including nisin
      concentration (viz. 50 ng/ml), growth phase of culture at which nisin be added
      (viz. at the early exponential phase), and the best time for analyzing the gene
      product after inoculation (viz. at the 3rd h), allowed the amylase product to be
      expressed in high amounts, constituting up to about 18% of the total
      intracellular protein. Furthermore, the signal peptide (SP) of amyL gene (SPamyL)
      from Bacillus licheniformis was ligated to the downstream of PnisA in pNICE,
      upgrading this vector to a NICE-secretion (NIES) level, which was then designated
      pNIES (Sec+, secretion positive). Characterization of pNIES using an amyL-SPDelta
      gene (amyL gene lacking its SP) as a reporter revealed the 3rd h after induction
      as the secretion peak of this system, at which the secretion efficiency and the
      amount of alpha-amylase being secreted into the culture supernatant were
      estimated to reach 77.6% and 27.75 mg/l. Expression and secretion of AmyL
      products by pNIES in Lb. reuteri was also confirmed by SDS-PAGE and
      immunoblotting analysis.

PMID- 16636440
TI  - Brassinosteroid signals control expression of the AXR3/IAA17 gene in the cross
      talk point with auxin in root development.
AB  - Transgenic plants overexpressing AXR3/IAA17 were impaired in root growth.
      Specifically, they exhibited severe defects in lateral root and root hair
      development similar to the root phenotypes of epi-brassinolide (epiBL)-treated
      wild-type plants. Here, we investigated the involvement of AXR3/IAA17 gene
      expression in brassinosteroid (BR)-regulated root development. Exogenous epiBL
      application significantly induced expression of the AXR3/IAA17 gene as well as
      several Aux/IAA genes, such as AXR2/IAA7, SLR/IAA14, and IAA28. We analyzed the
      transcription levels of several Aux/IAA genes related to root development in the
      BR signaling mutant bri1 and the BR biosynthesis mutant det2. AXR3/IAA17 gene
      expression was significantly decreased in bri1 plants. In det2 plants, expression
      of AXR3/IAA17 slightly decreased. This in turn suggests that epiBL induced these
      Aux/IAA genes, and that these induced gene products might function as factors in
      root development. Furthermore, AXR3/IAA17 might be involved in the BR signaling
      pathway, suggesting an intersection node of BR-auxin signaling in root
      development.

PMID- 16636441
TI  - Capsiate, a nonpungent capsaicin analog, increases endurance swimming capacity of
      mice by stimulation of vanilloid receptors.
AB  - We investigated the effect of capsiate, a nonpungent natural capsaicin analog, on
      the swimming capacity of mice in an adjustable-current water pool. Male BALB/c
      mice orally given capsiate (10 mg/kg) were able to keep swimming longer before
      exhaustion than the control mice. After 30 min of swimming, the residual glycogen
      in the gastrocnemius muscle was higher, the serum free fatty acid concentration
      tended to be higher, and the serum lactic acid concentration was significantly
      lower in the capsiate-administered mice. The value for the respiratory exchange
      ratio of the capsiate group was significantly lower during both resting and
      treadmill running. These physiological differences were abolished by
      administering the vanilloid receptor antagonist, capsazepin (0.17 mmol/kg, i.p.).
      The mice were not averse to the capsiate solution during a 4-h two-bottle choice
      test. These results suggest that the oral administration of capsiate enhanced fat
      oxidation and spared carbohydrate utilization, and consequently increased the
      endurance swimming capacity of the mice via stimulation of their vanilloid
      receptors. Practical application of capsiate is expected.

PMID- 16636442
TI  - The region in a subunit of the Aspergillus CCAAT-binding protein similar to the
      HAP4p-recruiting domain of Saccharomyces cerevisiae Hap5p is not essential for
      transcriptional enhancement.
AB  - The CCAAT-binding complex in Aspergillus species, known as the Hap complex,
      consists of at least three subunits, HapB, HapC, and HapE. Each Hap subunit
      contains an evolutionarily conserved core domain. In this study, a series of the
      truncated gene, which encodes the HapE subunit of Aspergillus oryzae, was
      constructed to survey the regions essential for the transcriptional enhancement
      of fungal genes. It was revealed that the non-conserved regions and the conserved
      region similar to the Hap4p recruiting domain of Saccharomyces cerevisiae were
      not necessary for Hap complex-mediated transcriptional enhancement.

PMID- 16636443
TI  - Relationship between the dough quality and content of specific glutenin proteins
      in wheat mill streams, and its application to making flour suitable for instant
      Chinese noodles.
AB  - The content of specific proteins such as high-molecular-weight glutenin subunits
      HMW-GS 5+10 and low-molecular-weight glutenin subunits LMW-GS KS2 in wheat mill
      streams of extra-strong Kachikei 33 wheat was quantified by SDS-PAGE and 2D-PAGE.
      The mill streams showed varied quantities of HMW-GS 5+10 (0.077 to 2.007 mg/g of
      mill stream), LMW-GS KS2 (0.018 to 0.586 mg/g of mill stream) and total protein
      (9.42% to 18.98%). The contents of these specific proteins in the mill streams
      were significantly correlated with the SDS sedimentation volume and the mixing
      properties, which are respective indices of specific loaf volume and dough
      strength. The contents of these specific glutenin proteins in the mill streams
      were therefore found to be significantly important for improving the dough
      quality suitable for bread and Chinese noodles. Accordingly, we present here the
      application of this information to the development of an effective method for
      producing mill streams with high quality and yield that are suitable for instant
      Chinese noodles.

PMID- 16636444
TI  - Cloning and comparison of third beta-glucoside utilization (bglEFIA) operon with
      two operons of Pectobacterium carotovorum subsp. carotovorum LY34.
AB  - A third bgl operon containing bglE, bglF, bglI, and bglA was isolated from
      Pectobacterium carotovorum subsp. carotovorum LY34 (Pcc LY34). The sequences of
      BglE, BglF, and Bgll were similar to those of the phosphotransferase system (PTS)
      components IIB, IIC, and IIA respectively. BglF contains important residues for
      the phosphotransferase system. The amino acid sequence of BglA showed high
      similarity to various 6-phospho-beta-glucosidases and to a member of glycosyl
      hydrolase family 1. Sequence and structural analysis also revealed that these
      four genes were organized in a putative operon that differed from two operons
      previously isolated from Pcc LY34, bglTPB (accession no. AY542524) and ascGFB
      (accession no. AY622309). The transcription regulator for this operon was not
      found, and the EII complexes for PTS were encoded separately by three genes
      (bglE, bglF, and bglI). The BglA enzyme had a molecular weight estimated to be
      57,350 Da by SDS-PAGE. The purified beta-glucosidase hydrolyzed salicin, arbutin,
      rhoNPG, rhoNPbetaG6P, and MUG, exhibited maximal activity at pH 7.0 and 40
      degrees C, and displayed enhanced activity in the presence of Mg2+ and Ca2+. Two
      glutamate residues (Glu178 and Glu378) were found to be essential for enzyme
      activity.

PMID- 16636445
TI  - Influence of dietary alpha-tocopheryl acetate supplementation on cholesterol
      oxidation in retail packed chicken meat during refrigerated storage.
AB  - This study examined the effect of dietary alpha-tocopheryl acetate on lipid and
      cholesterol oxidation in retail packed chicken meat during refrigerated storage.
      Male broiler chicks were randomly assigned to five pens containing 30 chicks
      each, which was subjected to one of five dietary treatments (0, 50, 100, 200, or
      400 IU of alpha-tocopheryl acetate/kg diet). Five different levels of alpha
      tocopherol were supplied to the chicks from 3 to 6 weeks. After 42 d of feeding
      all the broilers were slaughtered, and the carcasses were packed in polyethylene
      bags individually, bags similar to those used in the retail trade, and stored for
      12 d at 4 degrees C. Growth performance and fatty acid composition were not
      affected by the dietary alpha-tocopherol levels. The alpha-tocopherol content in
      breast and thigh muscles increased as the level of dietary alpha-tocopherol
      increased. The supplementation with 200 or 400 IU of alpha-tocopherol was more
      effective in reducing the level of lipid oxidation (P<0.05) and total cholesterol
      oxidation products (P<0.05). Therefore, an increase in the dietary alpha
      tocopherol level from 200 to 400 IU/kg feed causes major improvements in the
      oxidative stability of chicken meat during refrigerated storage.

PMID- 16636446
TI  - Effect of NaCl on the lipid peroxidation-derived aldehyde, 4-hydroxy-2-nonenal,
      formation in boiled pork.
AB  - Pork was boiled at 100 degrees C for 5, 10 and 15 min and stored at 0 degrees C,
      and changes in the 4-hydroxynonenal (HNE), malonaldehyde (MA) and fatty acid (FA)
      contents were analyzed immediately and 3 days later. The HNE, MA and FA contents
      in all samples were not significantly different from each other. Pork samples
      containing none (control), 1% and 2% NaCl were boiled at 100 degrees C for 5 min
      and stored at 0 degrees C, and changes in the HNE, MA and FA contents and cooking
      yields were immediately analyzed and after 0, 1, 2 and 3 days. Cooking losses in
      the NaCl-containing samples were significantly lower than those of the control.
      The HNE contents in the control samples of boiled pork had significantly
      increased after 3 days of storage, while the contents in the NaCl-containing
      samples were significantly lower than those of the control after 1, 2 and 3 days
      of storage. The MA contents in all samples were not significantly different from
      each other. All FA contents analyzed had decreased in all samples after 3 days of
      storage. The decrease ratio of highly unsaturated fatty acids was lowest in the
      sample containing 2% NaCl.

PMID- 16636447
TI  - Quantification of genetically modified soybeans using a combination of a
      capillary-type real-time PCR system and a plasmid reference standard.
AB  - Because the labeling of grains and feed- and foodstuffs is mandatory if the
      genetically modified organism (GMO) content exceeds a certain level of approved
      genetically modified varieties in many countries, there is a need for a rapid and
      useful method of GMO quantification in food samples. In this study, a rapid
      detection system was developed for Roundup Ready Soybean (RRS) quantification
      using a combination of a capillary-type real-time PCR system, a LightCycler real
      time PCR system, and plasmid DNA as the reference standard. In addition, we
      showed for the first time that the plasmid and genomic DNA should be similar in
      the established detection system because the PCR efficiencies of using plasmid
      DNA and using genomic DNA were not significantly different. The conversion factor
      (Cf) to calculate RRS content (%) was further determined from the average value
      analyzed in three laboratories. The accuracy and reproducibility of this system
      for RRS quantification at a level of 5.0% were within a range from 4.46 to 5.07%
      for RRS content and within a range from 2.0% to 7.0% for the relative standard
      deviation (RSD) value, respectively. This system rapidly monitored the labeling
      system and had allowable levels of accuracy and precision.

PMID- 16636448
TI  - Isolation and characteristics of methanosaeta in paddy field soils.
AB  - The population of filamentous acetate-utilizing methanogens in paddy field soils
      was 2.0 x 10(4) MPN/g dry soil in the submerged condition. They were able to form
      colonies in a deep agar medium, but not in a roll tube. Filamentous acetate
      utilizing methanogens isolated from Kanagi, Japan (strain K-5) and Tsukuba, Japan
      (strain T-3) were divided into two types based on length of filaments. One type,
      strain K-5, formed a short chain which was dispersed easily by weak shaking. The
      other type, strain T-3, formed a long chain, which formed cotton-like flocs and
      was not dispersed by weak shaking. They had sheaths composed of a pair of
      adjacent membranes on the outside of the cell membranes. The 16S rRNA gene
      similarities of strain T-3 and K-5 to Methanosaeta concilii strain Opfikon were
      100% and 99.5% respectively. Filamentous acetate-utilizing methanogens were also
      isolated from paddy field soils in various other regions of Japan. Our results
      suggest that Methanosaeta is universal in paddy soils and that it plays an
      important role in methane production from acetate.

PMID- 16636449
TI  - Preventive effect of egg yolk phosvitin on heat-insolubilization of egg white
      protein and its application to heat-induced egg white gel.
AB  - The effects of phosvitin (PV) on insolubilization of egg white protein (EWP) and
      ovotransferrin (OT) were examined by measuring turbidity after heating at 80
      degrees C in a pH range of 5 to 8. PV showed preventive ability against heat
      insolubilization of EWP, especially heat-labile OT. The preventive ability of PV
      was reduced by adding NaCl to a PV-OT mixture on heating. Native PAGE and gel
      filtration analyses showed that PV prevented an insolubilization of heat
      denatured OT through ionic interactions. The preventive effects of PV on
      insolubilization of EWP and OT resulted in the formation of a firm, transparent
      gel from EWP in coexistence with PV on heating. The addition of PV might make
      possible the preparation of liquid egg white without insoluble products even on
      heat-treatment at high temperatures.

PMID- 16636450
TI  - Soy protein suppresses gene expression of acetyl-coA carboxylase alpha from
      promoter PI in rat liver.
AB  - Dietary soy protein isolate (SPI) reduces hepatic lipogenesis by suppressing gene
      expression of lipogenic enzymes, including acetyl-CoA carboxylase (ACC). In order
      to elucidate the mechanism of this regulation, the effect of dietary SPI on
      promoter (PI and PII) specific gene expression of ACC alpha was investigated.
      Rats were fed experimental diets containing SPI or casein as a nitrogen source.
      SPI feeding decreased the hepatic contents of total ACC mRNA as well as
      triglyceride (TG) content, but dietary SPI affected the amount of sterol
      regulatory element binding protein (SREBP)-1 mRNA and protein very little. The
      amount of ACC mRNA transcribed from PII promoter containing SRE was not
      significantly affected by dietary protein, while a significant decrease in PI
      generated ACC mRNA content was observed in rats fed the SPI diet. These data
      suggest that SPI feeding decreased the hepatic contents of ACC alpha mRNA mainly
      by regulating PI promoter via a nuclear factor(s) other than SREBP-1.

PMID- 16636451
TI  - A novel type of formaldehyde-oxidizing enzyme from the membrane of Acetobacter
      sp. SKU 14.
AB  - Membrane-bound NADP-independent formaldehyde-oxidizing enzyme was purified to
      homogeneity from the membrane of Acetobacter sp. SKU 14 isolated in Thailand. The
      enzyme was solubilized from the membrane fraction of glycerol-grown cells with 1%
      Tween 20 at pH 2.85, and purified to homogeneity through the steps of column
      chromatographies on DEAE-Sephadex A-50 and Q-Sepharose in the presence of 0.1%
      Tween 20 and 0.1% Triton X-100. The enzyme purified together with a cytochrome c
      showed a single protein band on native-PAGE, and was dissociated into three
      different subunits upon SDS-PAGE with molecular masses of 78 kDa, 55 kDa, and 18
      kDa. The purified enzyme was finally characterized as a quinoprotein alcohol
      dehydrogenase (QADH), and this is the first indication that QADH highly oxidizes
      formaldehyde. The substrate specificity of the enzyme was found to be broad
      toward aldehydes and alcohols, and alcohols, especially n-butanol, n-propanol,
      and ethanol, were oxidized more rapidly than formaldehyde.

PMID- 16636452
TI  - Inhibitory effect of the saponins derived from roots of Platycodon grandiflorum
      on carrageenan-induced inflammation.
AB  - Previous studies have reported that the saponins isolated from the roots of
      Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), inhibited
      cyclooxygenase-2 (COX-2) expression in cultured lipopolysaccharide-activated
      macrophages. The aim of this presented study was to confirm the anti-inflammatory
      effects of CKS by examining their effect on the inflammatory response induced by
      carrageenan in a rat by using an acute air pouch inflammation model. CKS
      significantly reduced the levels of the inflammatory process markers in the air
      pouch, such as the volume of exudates, the amount of protein and the number of
      leukocytes and neutrophils. The levels of TNF-alpha and prostaglandin E2 (PGE2)
      were also markedly lower in the air pouch of the CKS-treated animals than in the
      controls. An immunoblot analysis showed that CKS reduced the COX-2 expression
      level in the exudate cells. In addition, CKS significantly reduced the paw edema
      induced by carrageenan and also markedly reduced the level of PGE2 production in
      the inflamed paw. These results suggest that CKS had significant anti
      inflammatory effects in vivo.

PMID- 16636453
TI  - Improved physical and biochemical features of a collagen membrane by conjugating
      with soluble egg shell membrane protein.
AB  - Soluble egg shell membrane protein (SEP) prepared from the egg shell membrane by
      performic acid oxidation and pepsin digestion was applied to prepare a membrane
      conjugated with pepsin-solubilized collagen (PSC) by cross-linking with water
      soluble carbodiimide. SEP enabled a conjugated membrane to be constructed with a
      well-developed network structure having thicker collagen fibrils and higher
      stability than the PSC membrane alone, as indicated by reduced solubility and
      collagenase-digestion, increased denaturation temperature, and superior
      flexibility. The SEP-PSC membrane (SEP:PSC of 1:1, w/w) had lower sweatiness than
      the PSC membrane. Fibroblasts and keratinocytes adhered to the SEP-PSC-coated
      wells (SEP:PSC of 1:10, w/w) as a fundamental model of an artificial skin similar
      to that to the PSC-coated wells due to similar expression level of several cell
      adhesion proteins. An SEP-PSC coating accelerated the cell growth of fibroblasts,
      whereas the cell growth of keratinocytes did not change, or decreased slightly
      due to more rapid differentiation indicated by a more substantial expression of
      differentiation marker proteins than a PSC-coating without SEP.

PMID- 16636454
TI  - Changes in soybean phytate content as a result of field growing conditions and
      influence on tofu texture.
AB  - It is known that tofu quality tends to vary among soybeans even of the same
      variety. Cultivation environments can affect the contents of the soybeans. Twenty
      seven soybean varieties were grown in a drained paddy field and an upland field,
      and then their protein and phytate contents were determined using the Fourier
      transfer infrared spectroscopy (FT-IR) method. The phytate contents of 12
      varieties were higher in the drained paddy field than in the upland field. On the
      other hand, the environmental factor had little effect on the protein contents.
      In order to determine whether the difference in phytate content affected tofu
      texture, the hardness of the tofu made from phytate-added soymilk was measured.
      The tofu texture having more phytate became softer in the range of the common
      coagulant concentration. We concluded that the difference in the phytate content
      of the soybeans among the environmental conditions is a factor that causes
      fluctuation in tofu quality.

PMID- 16636455
TI  - Mutational study on alphaGln90 of Fe-type nitrile hydratase from Rhodococcus sp.
      N771.
AB  - Nitrile hydratase (NHase) from Rhodococcus sp. N771 is a non-heme iron enzyme
      having post-translationally modified cysteine ligands, alphaCys112-SO2H and
      alphaCys114-SOH. We replaced alphaGln90, which is conserved in all known NHases
      and involved in the hydrogen-bond network around the catalytic center, with
      glutamic acid or asparagine. The kcat of alphaQ90E and alphaQ90N mutants
      decreased to 24% and 5% that of wild type respectively, but the effect of
      mutations on Km was not very significant. In both mutants, the alphaCys114-SOH
      modification appeared to be responsible for the catalysis as in native NHase. We
      crystallized the nitrosylated alphaQ90N mutant and determined its structure at a
      resolution of 1.43 A. The structure was basically identical to that of native
      nitrosylated NHase except for the mutated site and its vicinity. The structural
      difference between native and alphaQ90N mutant NHases suggested the importance of
      the hydrogen bond networks between alphaGln90 and the iron center for the
      catalytic activity.

PMID- 16636456
TI  - Changes in the mutagenic and estrogenic activities of 17beta-estradiol after
      treatment with nitrite.
AB  - We determined the changes in the mutagenic and estrogenic activities of 17beta
      estradiol after a nitrite treatment. Nitrite-treated 17beta-estradiol showed
      mutagenic activities toward Salmonella typhimurium strains TA 100 and TA 98. We
      confirmed that nitrite-treated 17beta-estradiol generated radicals from the
      results of an analysis of electron spin resonance. By applying an instrumental
      analysis, we identified 2-nitro-17beta-estradiol to have been formed in the
      reaction mixture. 2-Nitro-17beta-estradiol did not exhibit mutagenic activities
      toward Salmonella typhimurium strains, suggesting that other mutagens might have
      been formed in the reaction mixture. The clastogenic properties of nitrite
      treated 17beta-estradiol and 2-nitro-17beta-estradiol were analyzed by a
      micronucleus test with male ICR mice. Nitrite-treated 17beta-estradiol and 2
      nitro-17beta-estradiol induced a significantly higher frequency of micronucleated
      reticulocytes in mice. The estrogenic activity of 2-nitro-17beta-estradiol was
      found to be lower than that of 17beta-estradiol. These data suggest that a daily
      oral intake of 17beta-estradiol and nitrite might induce the formation of
      mutagenic compounds in our body.

PMID- 16636457
TI  - Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward
      cultured rat pheochromocytoma PC12 cells.
AB  - An extract of royal jelly (RJ) induced processes from cultured rat
      pheochromocytoma PC12 cells. Active components were isolated, and identified as
      adenosine monophosphate (AMP) and AMP N1-oxide. AMP N1-oxide was more than 20
      times as active as AMP, judging from the minimal concentration to elicit
      activity. AMP N1-oxide was thought to be responsible for about half of the
      process-forming activity of whole RJ. Chemically-synthesized AMP N1-oxide was
      active similarly to the molecule purified from RJ, confirming AMP N1-oxide as the
      active entity. AMP N1-oxide also suppressed proliferation of PC12 cells and
      stimulated expression of neurofilament M, a specific protein of mature neurons,
      demonstrating the stimulatory activity of AMP N1-oxide to induce neuronal
      differentiation of PC12 cells. Pharmacological experiments suggested that AMP N1
      oxide actions are mediated by adenyl cyclase-coupled adenosine receptors,
      including A2A. Thus AMP N1-oxide is a key molecule that characterizes RJ, and is
      not found in natural products other than RJ.

PMID- 16636458
TI  - Purification of glycogen debranching enzyme from porcine brain: evidence for
      glycogen catabolism in the brain.
AB  - Amylo-1,6-glucosidase from porcine brain was purified to homogeneity by ammonium
      sulfate fractionation, followed by sequential steps of liquid chromatography on
      DEAE-Sephacel, Sephacryl S-300, and Super Q. The purified enzyme had both
      maltooligosaccharide transferase and amylo-1,6-glucosidase activities within a
      single polypeptide chain, and the combination of these two activities removed the
      branches of phosphorylase limit dextrin. Based on these results, the purified
      enzyme was identified as a glycogen debranching enzyme (GDE). The molecular
      weight of the brain GDE was 170,000 by gel-filtration and 165,000 by reducing SDS
      PAGE. The pH profile of maltooligosaccharide transferase activity coincided with
      that of the amylo-1,6-glucosidase activity (pH optimum at 6.0). The existence of
      GDE as well as glycogen phosphorylase in the brain explains brain glycogenolysis
      fully and supports the hypothesis that glycogen is a significant source of energy
      in this organ.

PMID- 16636459
TI  - Crystallization of antiangiogenic Kringle V derived from human apolipoprotein A:
      crystallization applied to purification and formulation.
AB  - In this study, the Kringle V domain (Glu4225-Ser4310) of human apolipoprotein A,
      an antiangiogenic polypeptide, was expressed as a secreted form in Pichia
      pastoris, and was purified via a process consisting of three chromatographic
      steps. The chromatographically purified kringle V domain contained a C-terminal
      serine-deleted form and several high-molecular-weight forms, which were suspected
      to represent glycosylated derivatives. In order to remove these derivatives, we
      employed a crystallization process. The crystallization of kringle V resulted in
      an 85% recovery yield, and also resulted in the complete removal of the
      aforementioned high-molecular-weight forms. However, we were still able to detect
      a trace of the C-terminal serine-deleted form. The prepared Kringle V crystals
      were stable within a pH range of 7.0 to 8.0, and were completely dissolved by
      dilution, which is a crucial factor in the preparation of a highly concentrated
      formulation. The chromatogram of the crystallized kringle V on reversed-phase
      HPLC analysis was identical to that observed without crystallization. Also, we
      noted that the original anti-wound migration activities of the molecule toward
      human umbilical vein endothelial cells were completely retained.

PMID- 16636460
TI  - Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat.
AB  - Vitamin K (K) is essential for blood coagulation and bone metabolism in mammals.
      K acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic
      acid from glutamic acid residues. In addition to the liver and bone, K is found
      in the brain, heart, kidney and gonadal tissue. However, the physiological role
      of K in these various organs is not yet fully understood. It is likely that K has
      functions other than its role as a cofactor of protein gamma-glutamyl
      carboxylation. We used in this study the DNA microarray technique to identify the
      effect of K status on gene expression in the rat liver. The expression of genes
      involved in the acute inflammation response was enhanced in rats fed with a K
      deficient diet relative to the control and K1-supplemented diet groups. Moreover,
      dietary supplementation with K1 suppressed the inflammation induced by
      lipopolysaccharide administration. These results indicate that orally
      administrated K1 suppressed inflammation in the rat.

PMID- 16636461
TI  - Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose
      diet.
AB  - The effects of different levels of quercetin on the blood pressure were studied
      in 6-week-old male Sprague-Dawley rats. The rats were fed with a control diet or
      a high-fat high-sucrose (HFS) diet containing 0, 0.02, 0.07, 0.2, or 0.5%
      quercetin for 4 weeks. The systolic blood pressure and the lipid peroxides in the
      plasma were both higher in the rats fed with the HFS diet without quercetin than
      in the rats fed with the control diet. The nitric oxide synthase (NOS) activity
      in the vascular tissues and nitric oxide (NO) metabolites in the plasma and urine
      were both lower in these rats. A distinct depression of the increase in blood
      pressure was found in the rats fed with the HFS diets containing quercetin. Each
      level of quercetin examined was effective, the 0.5% level being much more
      effective than other levels. Dietary quercetin decreased lipid peroxidation in
      the plasma of the rats fed with the HFS diets. Quercetin also suppressed the
      decrease in NO metabolites in the plasma and urine, and the NOS activity in the
      vascular tissues of these rats. These results suggest that the increased NO
      availability caused by the elevated NOS activity, and the antioxidative activity
      in these rats fed with quercetin may be sources of the antihypertensive effect of
      quercetin.

PMID- 16636462
TI  - Enzymatic production of highly soluble myricitrin glycosides using beta
      galactosidase.
AB  - Myricitrin, a botanical flavonol glycoside, could be a useful ingredient of
      functional foods, cosmetics, and medicines because of its high anti-oxidative
      activity. However, due to its insolubility in water, it has a limited range of
      use. To improve this solubility, we glycosylated myricitrin by an enzymatic
      transglycosylate reaction. Myricitrin was galactosylated by beta-galactosidase
      from Bacillus circulans using lactose as a sugar donor. The reaction product was
      480 times more soluble than myricitrin. Four myricitrin galactosides were
      isolated from the reaction products by column chromatography, and their molecular
      structures were identified by using ESI-MS, 1H-NMR, 13C-NMR, 1H-1H COSY, 1H-13C
      HMQC and 1H-13C HMBC analysis. The solubility of these four myricitrin
      galactosides was more than 3.9 x 10(3) fold that of myricitrin, and each had
      similar anti-oxidative activity to that of myricitrin.

PMID- 16636463
TI  - Improved production of enzymes, which are expressed under the Pho regulon
      promoter, in the rmf gene (encoding ribosome modulation factor) disruptant of
      Escherichia coli.
AB  - Using a DNA macroarray, we investigated the effects of rmf gene (encoding
      ribosome modulation factor) disruption on gene expression profiles in Escherichia
      coli. This strain showed a phosphate-starvation-like response in gene expression
      even under phosphate sufficient conditions; significant upregulation of the Pho
      regulon genes was observed. Further, the production of alkaline phosphatase, a
      product of the Pho regulon gene, phoA, increased in the rmf disruptant under a Pi
      sufficient condition. Furthermore, production of PhoC acid phosphatase/nucleoside
      pyrophosphate phosphotransferase derived from Morganella morganii also increased
      significantly in the rmf disruptant. We concluded that host modification by the
      rmf gene disruption has potential benefit in industrial enzyme production using
      Escherichia coli.

PMID- 16636464
TI  - Potent odorants characterize the aroma quality of leaves and stalks in raw and
      boiled celery.
AB  - The raw and boiled odors of celery leaves and stalks were investigated. Among 12
      compounds identified as potent odorants, 3-n-butylphthalide 1, sedanenolide 2,
      and trans- and cis-sedanolides 3, 4 were assessed to be most contributive to the
      overall odor of celery. These three phthalides, (3E,5Z)-1,3,5-undecatriene,
      myrcene, and (E)-2-nonenal were common to both raw and boiled materials. Two
      compounds, ((Z)-3-hexenal and (Z)-3-hexenol), were dominant in raw materials and
      four compounds, (2-methylbutanoic acid, sotolon, beta-damascenone, and beta
      ionone), were dominant in boiled materials. Sensory evaluations were performed on
      natural celery odor and a series of reconstructed model aromas by assigning each
      intensity ratings for a set of seven odor qualities which aptly describe the
      odors of raw and boiled celery. According to the evaluation results, six common
      components contributed to the moderate odor of raw celery, two components
      dominant in raw materials enhanced the raw celery character, and four components
      dominant in boiled materials reduced the raw celery character and enhanced the
      boiled celery character. It was clarified that boiling-induced changes in celery
      odor were not affected by the amounts of phthalides, but by thermally generated
      compounds such as sotolon, beta-damascenone, and beta-ionone, which reduce the
      "green spicy" note.

PMID- 16636465
TI  - Identification of genes involved in the suppression of antibody production from
      human peripheral blood lymphocytes.
AB  - Pretreatment with L-leucyl-L-leucine methyl ester (LLME) is a prerequisite for
      peripheral blood mononuclear cells (PBMCs) to produce antigen-specific antibodies
      when sensitized with an antigen. Little information, however, is available
      regarding the mechanisms involved in LLME-induced augmentation of antibody
      production from PBMCs that are antigen sensitized. In the present study, we
      attempted to identify the genes involved in the suppression of antibody
      production from PBMCs that was not treated with LLME, but sensitized with an
      antigen. Using subtractive screening, we obtained 63 independent genes, including
      17 EST genes, that are specific for LLME-nontreated PBMC. Among these genes, the
      expression of heavy chain ferritin (H-ferritin), CC chemokine ligand 18 (CCL18),
      and matrix metalloproteinase 12 (MMP12) were augmented in LLME-nontreated PBMCs,
      suggesting that inflammatory factors might be involved in the suppression of
      antibody production in LLME-nontreated PBMCs.

PMID- 16636466
TI  - Substrate specificity of chitinases from two species of fish, greenling,
      Hexagrammos otakii, and common mackerel, Scomber japonicus, and the insect,
      tobacco hornworm, Manduca sexta.
AB  - Three chitinase isozymes, HoChiA, HoChiB, and HoChiC, were purified from the
      stomach of the greenling, Hexagrammos otakii, by ammonium sulfate fractionation,
      followed by column chromatography on Chitopearl Basic BL-03 and CM-Toyopearl
      650S. The molecular masses and pIs of HoChiA, HoChiB, and HoChiC are 62 kDa and
      pH 5.7, 51 kDa and pH 7.6, and 47 kDa and pH 8.8, respectively. Substrate
      specificities of these chitinases were compared with those of another fish
      stomach chitinase from the common mackerel, Scomber japonicus (SjChi), as well as
      two from the tobacco hornworm, Manduca sexta (MsChi535 and MsChi386). The
      efficiency parameters, kcat/Km, toward glycolchitin for HoChiA and SjChi were
      larger than those for HoChiB and HoChiC. The relative activities of HoChiA and
      SjChi toward various forms of chitin were as follows: shrimp shell or crab shell
      alpha-chitin > beta-chitin >> silkworm cuticle alpha-chitin. On the other hand,
      the relative activities of HoChiB and HoChiC were beta-chitin >> silkworm alpha
      chitin > shrimp and crab alpha-chitin. MsChi535 preferred silkworm alpha-chitin
      to shrimp and crab alpha-chitins, and no activity was observed toward beta
      chitin. MsChi386, which lacked the C-terminal linker region and the chitin
      binding domain, did not hydrolyze silkworm alpha-chitin. These results
      demonstrate that fish and insect chitinases possess unique substrate
      specificities that are correlated with their physiological roles in the digestion
      of food or cuticle.

PMID- 16636467
TI  - Immunochemical analysis of aquaporin isoforms in Arabidopsis suspension-cultured
      cells.
AB  - Aquaporins mediate the movement of water across biomembranes. Arabidopsis
      thaliana contains 35 aquaporins that belong to four subfamilies (PIP, TIP, SIP,
      and NIP). We investigated their expression profiles immunochemically in
      suspension-cultured Arabidopsis thaliana cells during growth and in response to
      salt and osmotic stresses. Protein amounts of all aquaporins were much lower in
      cultured cells than in the plant tissues. This is consistent with the low water
      permeability of protoplasts from cultured cells. After treatment with NaCl, the
      protein amounts of PIP2;1, PIP2;2, and PIP2;3 in the cells increased several
      fold, and those of TIP1;1 and TIP1;2, 15- and 3-fold respectively. PIP1 did not
      change under the stress. Cell death began after 19 d in culture, accompanied by
      marked accumulation of PIPs and TIPs and a gradual decrease in SIPs. Our results
      suggest the followings: (i) Accumulation of aquaporin isoforms was individually
      regulated at low levels in single cells. (ii) At least PIP2;2, PIP2;3, TIP1;1,
      and TIP1;2 are stress-responsive aquaporins in suspension cells. (iii) A sudden
      increment of several members of PIP2 and TIP1 subfamilies might be related to
      cell death.

PMID- 16636468
TI  - Comparison of enzymatic and antifungal properties between family 18 and 19
      chitinases from S. coelicolor A3(2).
AB  - Streptomyces coelicolor A3(2) has 13 chitinase genes encoding 11 family 18 and
      two family 19 chitinases. To compare enzymatic properties of family 19 chitinase
      and family 18 chitinases produced by the same organism, the four chitinases
      (Chi18bA, Chi18aC, Chi18aD, and Chi19F), whose genes are expressed at high levels
      in the presence of chitin, were produced in Escherichia coli and purified. The
      effect of pH on the hydrolytic activity was very different not only among the
      four chitinases but also among the substrates. The hydrolytic activity of Chi19F,
      family 19 chitinase, against soluble substrates was remarkably high as compared
      with three family 18 chitinases, but was the lowest against crystalline
      substrates among the four chitinases. On the contrary, Chi18aC, a family 18
      subfamily A chitinase, showed highest activity against crystalline substrates.
      Only Chi19F exhibited significant antifungal activity. Based on these
      observations, the roles of family 19 chitinases are discussed.

PMID- 16636469
TI  - Effect of heat treatment on the antioxidative and antigenotoxic activity of
      extracts from persimmon (Diospyros kaki L.) peel.
AB  - Heat treatment of persimmon peel (PP) increased the antioxidative activity of the
      70% ethanolic extract (EE) and water extract (WE) from PP. EE and WE both
      prevented H2O2-induced DNA damage to human peripheral lymphocytes. The
      antioxidative and antigenotoxic activities of the PP extracts were significantly
      affected by heating.

PMID- 16636470
TI  - Enhanced hypoglycemic activity following intratracheal administration of insulin
      microcrystal suspension with injection adjuvant.
AB  - The pulmonary route appears to be the most attractive alternative for non
      invasive systemic delivery of insulin. We have shown the feasibility of insulin
      microcrystals as a long-acting formulation for pulmonary delivery. In this study,
      we examined the effects of adjuvant for pulmonary formulations of insulin, such
      as protamine, zinc, and glycerol. In an in vivo experiment with rats, only zinc
      enhanced the hypoglycemic effect of insulin microcrystals, with 17% of minimum
      reductions in blood glucose (%MRBG) and a 44% decrement in the blood glucose
      level (D%9h).

PMID- 16636471
TI  - Effect of bleeding on hemoglobin contents and lipid oxidation in the skipjack
      muscle.
AB  - Skipjack samples were prepared using two different killing methods, namely,
      struggling death in iced sea water (control) and instant death by mechanical
      bleeding. The hemoglobin content in the bled muscles was significantly lower than
      that in the control. 4-Hydroxyhexenal content in the bled muscles was
      significantly lower than that in the control over 2 d of storage at 0 degrees C.

PMID- 16636472
TI  - Cytotoxic activity toward KB cells of 2-substituted naphtho[2,3-b]furan-4,9
      diones and their related compounds.
AB  - We investigated the cytotoxic activity of 2-substituted naphtho[2,3-b]furan-4,9
      diones. We have previously synthesized 33 types of 2-substituted and related
      compounds, and the cytotoxic activity of these compounds was then examined by a
      KB cell culture assay. 2-(3-Furanoyl)benzoic acids and 1,4-naphthoquinones had no
      activity. 2-Acetyl-4,9-dimethoxynaphtho[2,3-b]furan 4 showed low activity.
      However, parent naphtho[2,3-b]furan-4,9-dione 2 and most 2-substituted
      derivatives exhibited cytotoxic activity. The parent structure was therefore for
      cytotoxicity. 2-Formylnaphtho[2,3-b]furan-4,9-dione 11 had particularly potent
      activity (ED50=0.09 microg/ml).

PMID- 16636473
TI  - Specific characteristics of family 45 endoglucanases from Mucorales in the use of
      textiles and laundry.
AB  - We examined the characteristics of family 45 endoglucanases (glycoside hydrolases
      family 45; GH45) from Mucorales belonging to Zygomycota in the use of textiles
      and laundry. The defibrillation activities on lyocell fabric of family 45
      endoglucanases from Mucorales, such as RCE1 and RCE2 from Rhizopus oryzae, MCE1
      and MCE2 from Mucor circinelloides, and PCE1 from Phycomyces nitens, were much
      higher than those of the other family 45 endoglucanases. By contrast, family 45
      endoglucanases from Mucorales were less resistant to anionic surfactant and
      oxidizing agent, main components in detergents, than the other family 45
      endoglucanases. RCE1 consists of two distinct modules, a catalytic module and a
      carbohydrate-binding module family 1 (CBM1), and these common specific
      characteristics were considered to due to the catalytic module, but not to the
      CBM1.

PMID- 16636474
TI  - Comparisons of potentials for L-lysine production among different Corynebacterium
      glutamicum strains.
AB  - Corynebacterium glutamicum is an industrially important organism that is most
      widely used for the production of various amino acids. A defined L-lysine
      producing mutant was generated by introduction of the lysC mutation (T311I) into
      each of six representative C. glutamicum strains. The resulting six isogenic
      mutants were compared for L-lysine production under traditional 30 degrees C
      conditions and industrially more advantageous 40 degrees C conditions. It was
      found that there were significant differences in yield and productivity,
      especially at 40 degrees C. These results indicate the diversity among C.
      glutamicum strains in fermentative characters, as well as the importance of
      selecting a strain with industrially best performance.

PMID- 16636475
TI  - Steady-state kinetic characterization of evolved biphenyl dioxygenase, which
      acquired novel degradation ability for benzene and toluene.
AB  - Biphenyl dioxygenase (Bph Dox) catalyzes initial oxygenation in the bacterial
      biphenyl degradation pathway. Bph Dox in Pseudomonas pseudoalcaligenes KF707 is a
      Rieske type three-component enzyme in which a large subunit (encoded by the bphA1
      gene) plays an important role in the substrate specificity of Bph Dox. Steady
      state kinetic assays using purified enzyme components demonstrated that KF707 Bph
      Dox had a kcat/Km of 33.1 x 10(3) (M(-1) s(-1)) for biphenyl. Evolved 1072 Bph
      Dox generated by the process of DNA shuffling (Suenaga, H. et al., J. Bacteriol.,
      184, 3682-3688 (2002)) exhibited enhanced degradation activity not only for
      biphenyl (kcat/Km of 62.2 x 10(3) [M(-1) s(-1)]) but also for benzene and
      toluene, compounds that are rarely attacked by KF707 Bph Dox. These results
      suggest that evolved 1072 Bph Dox acquires higher affinities and catalytic
      efficiencies for various substrates than the original KF707 enzyme.

PMID- 16636476
TI  - Isolation of porphyran-degrading marine microorganisms from the surface of red
      alga, Porphyra yezoensis.
AB  - Marine microorganisms degrading porphyran (POR) were found on the surface of
      thalli of Porphyra yezoensis. Fifteen crude microorganism groups softened and
      liquefied the surface of agar-rich plate medium. Among these, 11 microorganism
      groups degraded porphyran that consisted of sulfated polysaccharide in Porphyra
      yezoensis. Following isolation, 7 POR-degradable microorganisms were isolated
      from the 11 POR-degradable microorganism groups.

PMID- 16636477
TI  - Growth inhibition by metabolites of gamma-hexachlorocyclohexane in Sphingobium
      japonicum UT26.
AB  - The growth of a gamma-hexachlorocyclohexane (gamma-HCH)-degrading bacterium
      Sphingobium japonicum (formerly Sphingomonas paucimobilis) UT26 in rich medium
      was inhibited by gamma-HCH. This growth inhibition was not observed in a mutant
      that lacked the initial or second step enzymatic activity for gamma-HCH
      degradation, suggesting that metabolites of gamma-HCH are toxic to UT26. Two
      metabolites of gamma-HCH, 2,5-dichlorophenol (2,5-DCP) and 2,5
      dichlorohydroquinone (2,5-DCHQ), showed a direct toxic effect on UT26 and other
      sphingomonad strains. Because only 2,5-DCP accumulated during gamma-HCH
      degradation, 2,5-DCP is thought to be a main compound for growth inhibition.

PMID- 16636478
TI  - Ursolic acid enhances cyclooxygenases and tumor necrosis factor-alpha expression
      in mouse skin.
AB  - An anti-inflammatory triterpenoid, ursolic acid (UA), has recently been found
      unexpectedly to induce the release of a pro-inflammatory mediator in resting
      macrophages. In this study, we found that topical applications of UA to mouse
      skin twice a week for 2 weeks significantly enhanced mRNA expression of
      cyclooxygenase (COX)-1, COX-2, and tumor necrosis factor-alpha, whereas its
      effect on tumor promotion was unclear.

PMID- 16636479
TI  - Vitamin B6 suppresses growth of the feline mammary tumor cell line FRM.
AB  - Growth of FRM cells was inhibited by the addition of pyridoxine in a dose
      dependent manner. Use of 5 mM pyridoxine caused an almost complete arrest of cell
      growth. Pyridoxal was as effective as pyridoxine, but pyridoxamine showed weak
      inhibitory action. Electron-microscopic examination of control cells revealed
      large nuclei and cellular membranes with villi, but, in pyridoxine-treated cells,
      condensed or degraded nuclei were observed. Many vacuoles and cholesterol
      crystals were widely distributed inside the cellular membrane of pyridoxine
      treated cells. One of the vacuoles was identified as a lipid droplet. The DNA
      ladder was observed in the pyridoxine-treated cells. It is suggested that
      pyridoxine treatment of FRM cells causes cytolysis of cells by apoptosis.

PMID- 16636480
TI  - Cloning and characterization of an RNase-related protein gene preferentially
      expressed in rice stems.
AB  - RNase-related proteins (RRPs) are S- and S-like RNase homologs lacking the active
      site required for RNase activity. Here we describe the cloning and
      characterization of the rice (Oryza sativa) RRP gene (OsRRP). A single copy of
      OsRRP occurs in the rice genome. OsRRP contains three introns and an open reading
      frame encoding 252 amino acids, with the replacement of two histidines involved
      in the active site of RNase by lysine and tyrosine respectively. OsRRP is
      preferentially expressed in stems of wild-type rice and is significantly down
      regulated in an increased tillering dwarf mutant ext37.

PMID- 16636481
TI  - Antiproliferative activity of root extract from gentian plant (Gentiana triflora)
      on cultured and implanted tumor cells.
AB  - We describe a novel pharmacological activity of the gentian root, an ingredient
      of Chinese medicines. Root extract from Gentiana triflora triggered cell death of
      human Daudi cells in culture. In addition, daily administration of the extract to
      mice inhibited growth of implanted solid tumors. Extract treatment of cultured
      cells resulted in the appearance of shranken, fragmented, or condensed cell and
      nuclear morphologies, and in chromosomal DNA degradation. But, the extract
      treated cells did not show DNA fragmentation, which exhibits a nucleosome ladder,
      suggesting that extract-triggered cell death is not mediated through a typical
      apoptotic pathway.

PMID- 16636482
TI  - Sex differences of risk factors for acute myocardial infarction in Japanese
      patients.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is prevalent and has serious
      consequences including re-infarction and death. Although the risk factors for AMI
      have been extensively studied in Western countries, they are less well documented
      in Japan. To determine the risk factors for AMI, we performed a case-control
      study in unselected patients with AMI. METHODS AND RESULTS: Risk factors were
      assessed in 1,925 consecutive patients with a first AMI (age, 28-103 years old;
      men, 1,353; women, 572), who were admitted to one of the major institutes in
      Japan, and in 2,279 age-and sex-matched population-based controls. Hypertension
      (odds ratio (OR), 4.80; 95% confidence interval (CI), 3.80 to 5.95; p < 0.01),
      diabetes (OR, 3.44; 95% CI, 2.50 to 4.75; p < 0.01), current smoking (OR, 3.39;
      95% CI, 2.78 to 4.18; p < 0.01), family history (OR, 1.84; 95% CI, 1.30 to 2.62;
      p < 0.01), and hypercholesterolemia (OR, 1.28; 95% CI, 1.00 to 1.62; p < 0.05)
      were all independent risk factors for AMI. However, obesity (OR, 1.13; 95% CI,
      0.92 to 1.50; NS) was not. Hypertension (OR, 4.80; 95% CI, 3.80 to 6.02; p <
      0.01), current smoking (OR, 4.00; 95% CI, 3.02 to 5.00; p < 0.01), and diabetes
      (OR, 2.9; 95% CI, 2.00 to 4.04; p < 0.01) were all independent risk factors for
      AMI in men. In contrast, only current smoking (OR, 8.22; 95% CI, 3.98 to 18.88; p
      < 0.01), diabetes (OR, 6.12; 95% CI, 3.78 to 12.02; p < 0.01), and hypertension
      (OR, 5.04; 95% CI, 2.92 to 7.52; p < 0.01) were independent risk factors for AMI
      in women. Hypercholesterolemia was an independent risk factor for AMI in men (OR,
      1.52; 95% CI, 1.00 to 1.98; p < 0.05), but not in women. CONCLUSIONS:
      Hypertension, diabetes, current smoking, family history and hypercholesterolemia
      are associated with AMI in Japanese patients, and the importance of the risk
      factors for AMI differs between men and women. Hypertension, current smoking,
      diabetes and family history are the most important risk factors in men, whereas
      current smoking, diabetes, hypertension and family history are the most important
      risk factors in women. Hypercholesterolemia is an independent risk factor for AMI
      in men, but not in women. To the best of our knowledge, this is the first
      clinical study to define the relative importance of risk factors for AMI in
      Japanese patients.

PMID- 16636483
TI  - Medium-term prognosis of young Japanese adults having acute myocardial
      infarction.
AB  - BACKGROUND: Data on the medium- and long-term prognosis of young Japanese
      patients with acute myocardial infarction (AMI) are still lacking. METHODS AND
      RESULTS: In the present study, 1,458 AMI patients were enrolled in the AMI-Kyoto
      Multi-Center Risk Study between January 2000 and December 2003. Of these,
      clinical characteristics and medium-term prognosis were retrospectively compared
      in 21 young patients < 40 years (young group), and 190 non-young patients 60-70
      years old (non-young group) who could be followed after hospital discharge. The
      young group was all male and had higher prevalence of current smoking and greater
      body mass index, but previous myocardial infarction (MI) and hypertension were
      more prevalent in the non-young group. The young group had a higher prevalence of
      single-vessel disease and a lesser incidence of left circumflex coronary artery
      as the culprit lesion. The acquisition rates of Thrombolysis In Myocardial
      Infarction 3 flow after primary percutaneous coronary intervention did not differ
      between the 2 groups, but the data of maximal creatine kinase was significantly
      higher in the young group. During the follow-up period (average 2.42 years for
      young, 2.37 years for non-young), survival and event-free survival rates and
      incidence of major adverse cardiac events (MACE) did not differ between the 2
      groups. The predictor of MACE during follow-up period was the presence of
      multivessel disease in the young group, whereas the presence of multivessel
      disease, history of previous MI and longer hospitalization were the predictors of
      MACE in the non-young group. CONCLUSIONS: These results suggest that the medium
      term prognosis in young AMI patients is comparable to that of non-young AMI
      patients in Japan.

PMID- 16636484
TI  - Clinical features of emergency electrocardiography in patients with acute
      myocardial infarction caused by left main trunk obstruction.
AB  - BACKGROUND: To diagnose left main trunk (LMT) infarction by 12-lead standard
      electrocardiogram (ECG) is an important emergency technique, but the features in
      LMT infarctions have not been clarified. METHODS AND RESULTS: The study enrolled
      140 subjects who were divided into 4 groups according to the location of the
      culprit artery: 35 with LMT, 35 with left anterior descending artery (LAD), 35
      with right coronary artery and 35 with left circumflex artery. Various parameters
      obtained from the ECGs were analyzed. Average QTc interval (0.51 +/- 0.06 s) in
      LMT group was markedly longer than that in the 3 other groups. Average QRS axis (
      10 +/- 77 degrees) in LMT infarction showed a remarkable left deviation. ST
      segment elevation in lead aVR occurred in 28 patients (80.0%) in the LMT group.
      The ECG features of the LMT group could be classified into 2 main groups: right
      bundle branch block (RBBB) with a marked left axis deviation (RBBB + LADEV type)
      and ST-segment elevation in leads V2-5, I and aVL without abnormal axis deviation
      (LAD type). CONCLUSION: Either ST-segment elevation in lead aVR and marked
      prolongation of both the QRS width and QTc interval with a prominent abnormal
      axis deviation or ST-segment elevation in the broad anterior precordial lead with
      a normal QRS axis strongly suggests LMT infarction.

PMID- 16636485
TI  - Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial
      infarction patients following primary coronary angioplasty.
AB  - BACKGROUND: The predictors of cardiac rupture (CR) in patients with acute
      myocardial infarction (AMI) treated with successful primary coronary angioplasty
      have not been identified. METHODS AND RESULTS: Of 433 consecutive AMI subjects
      who underwent reperfusion by primary coronary angioplasty within 24 h of onset,
      CR occurred in 11 (2.5%), free wall rupture in 9, and ventricular septal
      perforation in 2. Rates of females, diabetes mellitus and anterior infarction
      were higher in the group of CR patients than in the others (p < 0.05). There were
      no significant differences between the 2 groups in terms of left ventricular (LV)
      function soon after recanalization, such as LV ejection fraction, regional wall
      motion, or end-diastolic volume index. Plasma levels of both high-sensitivity C
      reactive protein (hsCRP) and serum amyloid-A protein (SAA) were significantly
      higher in the CR patients than in the others (hsCRP: 6.7 +/- 6.7 mg/dl vs 3.3 +/-
      3.8 mg/dl, p = 0.007; SAA: 699 +/- 812 microg/dl vs 208 +/- 273 microg/dl, p <
      0.0001). Multivariate analysis identified SAA as an independent predictor of CR
      (risk ratio: 8.8, 95% confidence interval: 1.7-25.6, p < 0.05). Conclusions In
      patients with AMI treated with primary coronary angioplasty, inflammation may be
      closely related to CR, for which SAA is a useful predictor.

PMID- 16636486
TI  - Angiographic and clinical outcome in ST-segment elevation myocardial infarction
      patients receiving an adjunctive double bolus regimen of tirofiban for primary
      percutaneous coronary intervention.
AB  - BACKGROUND: Because of different dosages, the efficacy of adjunctive tirofiban
      therapy for primary percutaneous coronary intervention (PCI) is currently
      unclear. The hypothesis that a double bolus regimen of tirofiban will improve
      angiographic and clinical outcomes in patients with ST-segment elevation acute
      myocardial infarction (STEMI) undergoing PCI was tested in the present study.
      METHODS AND RESULTS: Primary PCI was performed in 217 STEMI patients: 80 received
      standard PCI (control group) and 137 received tirofiban (tirofiban group).
      Tirofiban was given as a bolus (10 mg/kg) in the emergency room and again upon
      arrival at the cardiac catheterization laboratory, followed by infusion of 0.15
      mg . kg(-1) . min (-1) until the total dose reached 12.5 mg. The primary endpoint
      was emergency target vessel revascularization, recurrent myocardial infarction,
      or cardiovascular mortality at 30 days and 1 year. Baseline clinical and
      angiographic variables of the 2 groups were similar, as were angiographic results
      after PCI and bleeding complications at 30 days. The primary 30-day and 1-year
      endpoints were 5.1% and 11.7% in the tirofiban group, respectively, vs 10.0% (p =
      0.171) and 18.8% (p = 0.151) in the control group. CONCLUSION: Although
      angiographic and clinical benefits were not demonstrated, the results suggest
      that research into an effective and uniform dosing regimen of adjunctive
      tirofiban therapy for PCI is warranted.

PMID- 16636487
TI  - Potential risk factors and incidence of pulmonary thromboembolism in Japan:
      results from an overview of mailed questionnaires and matched case-control study.
AB  - BACKGROUND: The potential risk factors for pulmonary thromboembolism (PTE) have
      not been examined in Japan, so the aims of the present study were to assess
      independent risk factors for PTE, and to estimate the recent incidence of
      symptomatic PTE. METHODS AND RESULTS: Based on a mailed questionnaire, the
      potential risk factors for PTE were prospectively assessed using a matched case -
      control study, and the number of new patients with PTE in 2004 was calculated
      prospectively. In multivariate analyses, increase in body mass index (odds ratio
      (OR) = 2.85 by 10 kg/m2; 95% confidence interval (CI), 1.51-5.39), prolonged
      immobilization (OR, 8.14; 95% CI, 3.15-20.99), recent major surgery (OR, 6.78;
      95% CI, 2.65-17.32), and cancer (OR, 2.72; 95% CI, 1.25-5.95) were identified as
      independent risk factors for PTE in Japan. The risks for atherosclerosis
      (diabetes mellitus, hypertension, hyperlipidemia, and smoking), and alcohol
      consumption did not affect the incidence of PTE. The calculated number of new
      patients with PTE per year was 4,108 (95% CI, 3,564-4,712) in 2004. CONCLUSION:
      The independent risk factors for PTE in Japan are body mass index, prolonged
      immobilization, recent major surgery, and cancer. The number of new patients with
      PTE in 2004 did not demonstrate an upward trend compared with 2000.

PMID- 16636488
TI  - Valsartan cardio-renal protection in patients undergoing coronary angiography
      complicated with chronic renal insufficiency (VAL-CARP) trial: rationale and
      design.
AB  - BACKGROUND: Despite an increase in the frequency of coronary angiography (CAG) in
      Japan, the exact incidence of contrast-induced nephropathy (CIN) remains unknown
      in the Japanese population, especially in patients with chronic renal
      insufficiency. In addition, the nature of pharmacological interventions that
      would benefit the patients before or after procedures such as coronary bypass
      graft (CABG) and percutaneous coronary intervention (PCI) has not been fully
      investigated. METHODS: In the trial 500 patients with renal insufficiency
      (defined as a glomerular filtration rate (GFR) of between 89 and 30 ml . min(-1)
      . (1.73 m(-2)) following CAG will be randomly assigned to receive either
      valsartan, an angiotensin receptor blocker or angiotensin converting enzyme (ACE)
      inhibitor plus valsartan.1 The primary end-point is a change in the GFR of
      patients, which will be followed up for 3 years, including following CABG surgery
      or PCI. The incidence of cardiac events as well as the adverse effects of
      pharmacological intervention will be evaluated. In addition, the incidence of
      renal artery stenosis at the time of CAG will be reported also; however, the
      patients with renal artery stenosis will be excluded from the present study.
      CONCLUSION: The present study will provide data on: 1) the exact incidence and
      course of renal function of CIN after CAG; and 2) the comparative therapeutic
      benefit of pharmacological intervention with valsartan alone or with valsartan
      and an ACE inhibitor in combination in patients with coexisting coronary artery
      diseases and chronic renal insufficiency, regardless of whether they receive CABG
      or PCI. In addition to these studies, an estimate of the incidence of renal
      artery stenosis in these patients will be demonstrated.

PMID- 16636489
TI  - Prophylactic hemodialysis does not prevent contrast-induced nephropathy after
      cardiac catheterization in patients with chronic renal insufficiency.
AB  - BACKGROUND: In Japan, prophylactic hemodialysis has been considered useful for
      preventing contrast-induced nephropathy (CIN). METHOD AND RESULTS: To assess
      whether hemodialysis prevented CIN, 391 patients (age: 69 +/- 8 years, 63
      females) with chronic renal insufficiency (CRI, serum creatinine level (Scr) > or
      = 1.3 mg/dl) who underwent cardiac catheterization, were retrospectively
      analyzed. Patients were divided into 3 categories based on Scr: L (1.3 > or = Scr
      < 2.0 mg/dl, n = 332); M (2.0 > or = Scr < 3.0 mg/dl, n = 49); and H (Scr > or =
      3.0 mg/dl, n = 10). To prevent CIN, 35 category M patients and all category L
      patients received hydration alone, whereas 14 category M patients and all
      category H patients received hemodialysis. CIN developed in 48 patients. The
      incidence of CIN in category H was significantly higher than that in category L
      or M (H, 40% vs L, 11% or M, 16% (p < 0.05)). In category M patients treated with
      hemodialysis, Scr increased from 2.4 +/- 0.3 to 3.0 +/- 0.5 mg/dl (p < 0.05)
      within 7 days, and 29% of patients developed CIN. However, in category M patients
      who did not receive hemodialysis, the Scr did not change (pre, 2.3 +/- 0.2 mg/dl
      to post, 2.2 +/- 0.4 mg/dl), and the incidence of CIN was 11%. CONCLUSION:
      Prophylactic hemodialysis for CRI patients undergoing cardiac catheterization
      does not prevent CIN.

PMID- 16636490
TI  - Intra-individual variability of high-sensitivity C-reactive protein: age-related
      variations over time in Japanese subjects.
AB  - BACKGROUND: Prospective studies have demonstrated a direct association between
      the baseline level of high-sensitivity C-reactive protein (hsCRP) and the risk of
      developing cardiovascular disease. The potential for hsCRP variability during the
      follow-up interval is of great interest, so the repeatability of measurements of
      hsCRP in men and women, and in different age groups, was investigated in the
      present study. METHODS AND RESULTS: The measurement of hsCRP was performed in 899
      male and 780 female Japanese civil servants aged 18-60 years in the spring of
      2004 and 2005. Within-subject repeatability and intra-class correlation
      coefficient of reliability were used to characterize the variation in
      measurements. Error of the measurement process was negligible, as the analytical
      variance was 0.0003 [ln(mg/L)] [ln(mg/L)] with a reliability coefficient of
      0.997. In contrast, the within-subject variation of hsCRP was considerable with a
      reliability coefficient of 0.61 in both sexes and repeatability coefficients of
      5.25 and 5.38 in men and women, respectively. The variation differed with age,
      especially in women, as less variation was observed in subjects over 40 years of
      age during the follow-up interval. CONCLUSIONS: The results suggest that a single
      measurement of hsCRP is subject to considerable but equal within-subject
      variation over time in men and women, and this variation differs among the age
      groups, which may affect the risk assessment of hsCRP in association with future
      cardiovascular events.

PMID- 16636491
TI  - Diagnostic accuracy of 64-slice computed tomography for detecting
      angiographically significant coronary artery stenosis in an unselected
      consecutive patient population: comparison with conventional invasive
      angiography.
AB  - BACKGROUND: Multislice computed tomography (MSCT) is a promising noninvasive
      method of detecting coronary artery disease (CAD). However, most data have been
      obtained in selected series of patients. The purpose of the present study was to
      investigate the accuracy of 64-slice MSCT (64 MSCT) in daily practice, without
      any patient selection. METHODS AND RESULTS: Using 64-slice MSCT coronary
      angiography (CTA), 69 consecutive patients, 39 (57%) of whom had previously
      undergone stent implantation, were evaluated. The mean heart rate during scan was
      72 beats/min, scan time 13.6 s and the amount of contrast media 72 mL. The mean
      time span between invasive coronary angiography (ICAG) and CTA was 6 days.
      Significant stenosis was defined as a diameter reduction of > 50%. Of 966
      segments, 884 (92%) were assessable. Compared with ICAG, the sensitivity of CTA
      to diagnose significant stenosis was 90%, specificity 94%, positive predictive
      value (PPV) 89% and negative predictive value (NPV) 95%. With regard to 58
      stented lesions, the sensitivity, specificity, PPV and NPV were 93%, 96%, 87% and
      98%, respectively. On the patient-based analysis, the sensitivity, specificity,
      PPV and NPV of CTA to detect CAD were 98%, 86%, 98% and 86%, respectively. Eighty
      two (8%) segments were not assessable because of irregular rhythm, calcification
      or tachycardia. CONCLUSION: Sixty-four-MSCT has a high accuracy for the detection
      of significant CAD in an unselected patient population and therefore can be
      considered as a valuable noninvasive technique.

PMID- 16636492
TI  - Positive pressure ventilation treatment reduces plasma levels of amino terminal
      pro brain natriuretic peptide in congestive heart failure patients with sleep
      apnea.
AB  - BACKGROUND: The purpose of the present study was to assess the short-term effects
      of positive pressure ventilation (PPV) on plasma amino terminal-pro brain
      natriuretic peptide (NT-proBNP) levels in patients with congestive heart failure
      (CHF) and sleep apnea (SA). METHODS AND RESULTS: Polysomnography was performed in
      105 CHF patients. Twenty-six patients with CHF and SA were randomly assigned to a
      control group or a PPV group. Patients in the higher New York Heart Association
      classes had higher plasma levels of NT-proBNP. The plasma NT-proBNP concentration
      in the PPV group decreased. CONCLUSION: Plasma NT-proBNP levels reflect the
      severity of CHF, and PPV can decrease plasma NT-proBNP levels in patients with
      CHF and SA.

PMID- 16636493
TI  - Disorganization of gap junction distribution in dilated atria of patients with
      chronic atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is an arrhythmia associated with functional
      and morphological remodeling of atria. We investigated the distribution and the
      expression of connexins in atrial tissues from patients with chronic AF and left
      atrial dilatation (AD). METHODS AND RESULTS: Immunohistochemistry was performed
      in atrial tissues obtained during cardiac surgery from patients with chronic AF +
      AD (n = 11), sinus rhythm (SR, n = 11) and SR + AD (n = 4). In SR patients
      (control), the connexin (Cx) 43 labeling of the intercalated disks seen en-face
      was characterized by small central spots surrounded by larger spots at the
      periphery. In the left atria from AF + AD patients, the area of the intercalated
      disk was significantly enlarged. Although peripheral Cx43 labeling was preserved,
      there was a striking loss of central labeling spots. The area occupied by gap
      junctions was slightly but significantly larger than that of the control. The
      left atria from patients with SR + AD showed gap junction disorganization
      analogous to AF + AD. The labeling patterns of Cx40 were essentially similar to
      those of Cx43. Conclusions In chronic AF with AD, gap junctions at the
      intercalated disk are disorganized, resulting most likely from AD but not from AF
      itself. This gap junction remodeling might be involved in altered atrial
      conduction properties, but its potential arrhythmogenic role remains unclear.

PMID- 16636494
TI  - Comparison of efficacy of sotalol and nifekalant for ventricular
      tachyarrhythmias.
AB  - BACKGROUND: Suppression of implantable defibrillator discharges associated with
      ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed
      to investigate the efficacy of intravenous nifekalant hydrochloride in predicting
      the effects of oral sotalol. METHODS AND RESULTS: The present study included 14
      patients who had sustained VTA associated with structural heart disease. All
      patients also had inducible VTA. To compare the effects of nifekalant and
      sotalol, programmed electrical stimulation was performed, in the basal state,
      after nifekalant administration, and after sotalol administration. Nifekalant and
      sotalol similarly prolonged the corrected QT interval and ventricular effective
      refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5
      patients whose VTA became non-inducible by nifekalant, subsequent treatment with
      sotalol also suppressed the inducible VTA. In all of the 9 patients non
      responding to nifekalant, VTA remained inducible during sotalol treatment.
      Nifekalant accurately predicted the response to sotalol during electrophysiologic
      study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred
      in 3 non-responders during a follow-up of 46 +/- 11 months. CONCLUSIONS:
      Nifekalant and sotalol had similar effects on inducible VTA. The response of
      inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

PMID- 16636495
TI  - Heart failure elevates serum levels of cibenzoline in arrhythmic patients.
AB  - BACKGROUND: Cibenzoline dosing is generally based on renal function, but serum
      concentrations might be greater than the expected therapeutic levels when
      standard oral dosing is used. Because heart failure might modify cibenzoline
      pharmacokinetics, the difference in cibenzoline pharmacokinetics between patients
      with and without heart failure was evaluated. METHODS AND RESULTS: The study
      enrolled 368 patients (233 men, 135 women) that had been hospitalized and
      received cibenzoline therapy at the National Cardiovascular Center from January
      2001 to May 2005. There were 89 patients with heart failure (51 men, 38 women)
      and 279 patients without heart failure (182 men, 97 women). They had therapeutic
      drug monitoring > or = 3 days after the beginning of treatment with cibenzoline.
      Brain natriuretic peptide (BNP) was measured in 81 patients (50 men, 31 women)
      concurrently with therapeutic drug monitoring of cibenzoline. The difference in
      serum cibenzoline concentration/(dose/weight) (C/D) values between patients with
      and without heart failure was analyzed using analysis of covariance (ANCOVA) with
      creatinine clearance (Ccr) serving as the covariate. The effects of dose/weight
      and the log-transformed BNP (log-BNP) values on serum cibenzoline concentrations
      were also assessed using ANCOVA. There were 135 and 361 measurements of serum
      cibenzoline concentration in patients with and without heart failure,
      respectively. Pearson's correlation coefficient analyses in the patients with and
      without heart failure revealed that the C/D values were significantly correlated
      with Ccr (with heart failure, y = -0.837x + 169, r = -0.211, p = 0.014; without
      heart failure, y = -0.789x + 132, r = -0.393, p < 0.001), and the ANCOVA model
      indicated that C/D values were significantly higher in patients with heart
      failure than without heart failure. The ANCOVA model also showed that
      dose/weight, Ccr and the log-BNP value were significant factors. CONCLUSIONS: The
      selection of a cibenzoline dose based only on renal function may increase the
      risk of toxicity in patients with heart failure. Cardiac function should be taken
      into account in cibenzoline dosing. The log-BNP may be a useful index for
      predicting serum cibenzoline concentrations.

PMID- 16636496
TI  - Cigarette smoking induced oxidative stress may impair endothelial function and
      coronary blood flow in angiographically normal coronary arteries.
AB  - BACKGROUND: Smoking contributes to the progression of atherosclerotic heart
      disease by causing endothelial dysfunction. In the present study the effect of
      smoking on endothelial functions and coronary flow was investigated, as well as
      the relationship of these factors with oxidative stress parameters, in subjects
      with normal coronary arteries. MATERIALS AND RESULTS: The study group comprised
      87 patients with angiographically normal coronary arteries (36 smokers, 51
      nonsmokers). Coronary flow patterns were determined by the Thrombolysis In
      Myocardial Infarction (TIMI) frame count method. Endothelial function was
      evaluated by high-frequency ultrasound imaging of the brachial artery. Superoxide
      dismutase (SOD) and reduced glutathione (GSH) and reduction of oxidative material
      in the body and the endproduct of lipid peroxidation, malondialdehyde (MDA), were
      measured as oxidative stress markers. Mean TIMI frame count was significantly
      higher in smokers than nonsmokers (42.2 +/- 16 vs 29.5 +/- 9.5, p = 0.0001).
      Endothelium-dependent flow-mediated dilatation was 6.81+/-1.95% in nonsmokers and
      5.7 +/- 2.2% in smokers (p = 0.0001). The smokers had dramatically higher levels
      of SOD and MDA and lower levels of GSH than the nonsmoker group. CONCLUSION:
      Smoking induced oxidative stress deteriorates coronary blood flow by disturbing
      endothelial function.

PMID- 16636497
TI  - P-selectin expression, but not GPIIb/IIIa activation, is enhanced in the
      inflammatory stage of Takayasu's arteritis.
AB  - BACKGROUND: Inflammation and thrombosis are closely related processes, but the
      association between disease activity and thrombogenicity in Takayasu's arteritis
      (TA) is poorly understood. To investigate the link between platelet activation
      and disease activity, flow cytometric analyses of platelet P-selectin and
      activated GPIIb/IIIa expression were performed in patients with TA. METHODS AND
      RESULTS: Twenty-two patients with TA, classified into active (Group A, n = 9) and
      inactive (Group I, n = 13) according to blood-derived inflammatory markers, and
      14 healthy age- and gender-matched controls (Group C) were studied. Compared with
      Group C, the mean fluorescence intensity of P-selectin in response to 0.1-10
      micromol/L of ADP was significantly upregulated in Group A, but not in Group I.
      No differences in platelet GPIIb/IIIa expression in stimulated platelets were
      seen among the 3 groups. Standard platelet aggregation studies revealed that
      disease activity did not influence platelet aggregation by ADP. CONCLUSIONS: P
      selectin expression, but not activated GPIIb/IIIa, is enhanced in ADP-activated
      platelets from patients in the inflammatory stage of TA. P-selectin may play a
      significant role in the inflammatory and thrombotic responses associated with
      intractable TA, presumably by inducing platelet-leukocyte interactions.

PMID- 16636498
TI  - Tumor necrosis factor-alpha downregulates the voltage gated outward K+ current in
      cultured neonatal rat cardiomyocytes: a possible cause of electrical remodeling
      in diseased hearts.
AB  - BACKGROUND: Inflammatory cytokines have been reported to contribute to the
      progression of cardiac remodeling in various heart diseases and a remarkable
      prolongation of the monophasic action potential duration and reductions in the
      expression of Kv4.2 and K+ channel-interacting protein-2 (KChIP-2) in a rat
      autoimmune myocarditis model have been documented. In this study, the effect of
      tumor necrosis factor-alpha (TNF-alpha) on cultured cardiomyocytes was evaluated,
      focusing on the change in the voltage-gated outward K+ current and expression of
      related molecules. METHODS AND RESULTS: Cardiomyocytes isolated from 1-day-old
      Lewis rats were cultured for 72 h and treated with TNF-alpha (50 ng/ml) for an
      additional 48 h. The myocytes treated with TNF-alpha showed a 22% reduction in
      the peak K+ current, which consisted of a transient outward K+ current (Ito) and
      1.4-fold enhancement of the cell-capacitance in comparison with the control.
      Among the cardiac ion channel related molecules evaluated in this study, Kv4.2
      and KChIP-2 mRNA exhibited remarkable reductions (p < 0.05). CONCLUSIONS:
      Treatment with TNF-alpha induced reductions in Ito as well as cellular
      hypertrophy in neonatal cultured myocytes, which indicates that TNF-alpha might
      play a role in promoting electrical remodeling of cardiomyocytes under
      inflammatory conditions.

PMID- 16636499
TI  - Molecular and electrophysiological differences in the L-type Ca2+ channel of the
      atrium and ventricle of rat hearts.
AB  - BACKGROUND: Many pathological conditions induce electrical remodeling, possibly
      through intracellular Ca2+ overload, but the currently available L-type Ca2+
      channel blockers may be detrimental because of their global negative inotropic
      effects. METHODS AND RESULTS: To determine whether the L-type Ca2+ channel is
      identical throughout the heart, the distribution of the mRNAs and proteins
      comprising the L-type Ca2+ channel and its electrophysiological properties were
      analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was
      more abundantly expressed in the atrium (approximately 5-fold) than in the
      ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less
      abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was
      decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was
      increased (approximately 2-fold) in the atrium compared with the ventricle.
      Although the peak ICa,L density showed no significant differences, voltage
      dependence of inactivation and activation of the current showed a more
      depolarized shift in the atrium than in the ventricle. CONCLUSION: These results
      indicate that in the rat heart the L-type Ca2+ channel differs between the atrium
      and ventricle with regard to gene expression and electrophysiological properties.

PMID- 16636500
TI  - RECS1 is a negative regulator of matrix metalloproteinase-9 production and aged
      RECS1 knockout mice are prone to aortic dilation.
AB  - BACKGROUND: RECS1 is a mechanical stress responsive gene and RECS1 knockout (KO)
      mice (older than 14 months) are prone to cystic medial degeneration (CMD). The
      present study was designed to assess whether RECS1 KO mice have altered
      gelatinase (matrix metalloproteinase (MMP)-2 and MMP-9) levels and whether they
      are prone to aortic dilation. METHODS AND RESULTS: Aortic and plasma gelatinase
      levels in RECS1 KO and wild-type (WT) mice were assessed by gelatin zymography
      and Western blot analysis. Pro-MMP-9 (in the aorta), neutrophil gelatinase
      associated lipocalin/MMP-9 complex (NGAL-MMP-9, in plasma), and active-MMP-9
      protein levels were more abundant in KO mice throughout adulthood compared with
      WT mice. Aortic MMP-2, aortic MMP-9, and plasma MMP-9 activation increased with
      age, even though the aortic pro-MMP-9, plasma NGAL-MMP-9, aortic and plasma pro
      MMP-2 production decreased: this was true both for the WT and KO animals. Aortic
      pro-MMP-2, aortic active-MMP-2, and plasma pro-MMP-2 protein levels were higher
      in the aged KO mice, but they were lower in the young KO mice than those in WT
      mice. Thoracic aortic dilation was observed only in the aged KO mice. In situ
      zymographic experiments confirmed that the increased aortic gelatinase activities
      were associated with CMD and aortic dilation observed in the aged KO mice.
      CONCLUSIONS: RECS1 negatively regulates aortic MMP-9 production and knocking out
      RECS1 induces susceptibility to aortic dilation as well as CMD in the aged mice.
      The present study suggests that RECS1 plays protective roles in vascular
      remodeling. We speculate that inhibiting unfavorable deposition and extracellular
      matrix degradation are both important for prevention and treatment of aneurysms.

PMID- 16636501
TI  - Pretreatment with transmyocardial revascularization might improve ischemic
      myocardial function performed with cell transplantation.
AB  - BACKGROUND: Cells transplanted into the myocardial infarct areas might be lost
      because of the lack of blood supply to these myocardium areas. The hypothesis
      that pretreatment with angiogenic therapy induced by transmyocardial
      revascularization (TMR) might improve ischemic myocardial function, followed by
      cell transplantation was tested. METHODS AND RESULTS: After the ligation of the
      left anterior descending coronary artery, rats were treated with TMR. Two weeks,
      embryonic stem cells were transplanted into an injured heart. Four weeks after
      cell transplantation, cardiac function was assessed by homodynamic measurements.
      Capillary density and infarct size in the infarct myocardium were measured by
      using a previous experimental method. Graft histology and morphology was also
      evaluated. Four weeks after the operation, myocardial infarct (MI) rats treated
      with TMR and cell transplantation showed significantly higher cardiac function in
      hemodynamic measurements (p < 0.01) than that of MI rats receiving cell
      transplantation or TMR alone. A significant increase in capillary density and
      reduction in infarct size was observed in the MI rats that received a combined
      therapy (p < 0.01). CONCLUSION: Pretreatment of an infarct region of the heart
      with angiogenesis induced by TMR can enhance the efficacy of a cell graft and
      attenuate the progression of cardiac dysfunction in the rat model.

PMID- 16636502
TI  - Tricuspid pouch can cause systemic embolization in adulthood.
AB  - A 63-year-old-man with significant left hemiplegia was admitted to hospital. He
      had experienced a transient cerebral ischemic attack 10 years ago. Computed
      tomography revealed hypodensity along the right lateral ventricle, which
      corresponded to the left paralysis. Echocardiography and left ventricular
      angiography revealed an aneurysm of the membranous septum (AMS) without a
      ventricular septal defect (VSD). Therefore, the embolism was thought to be of
      cardiac origin, but surgery revealed that it was not caused by AMS. The aneurysm
      was created when the septal leaflet of tricupid valve formed a giant capsule
      during the process of natural closure of the VSD. It was a large pouch, 2.0 cm in
      diameter, adjacent to the septal leaflet. Anomalies of the tricuspid valve,
      including pouches, can resemble AMS.

PMID- 16636503
TI  - Hemodynamic consequences of a swinging, infarcted ventricular septum.
AB  - Noonan syndrome presents with dysmorphic facial features, short stature, and
      cardiac abnormalities (most commonly pulmonic stenosis and hypertrophic
      cardiomyopathy). This report describes a rare case accompanied by a secundum
      atrial septal defect (ASD) and a ventricular septal aneurysm causing right
      ventricular (RV) pressure gradient. A 29-year-old mentally retarded man was
      admitted to hospital with exertional dyspnea. His somatic features included short
      stature (148 cm), hypertelorism, a shield chest, and thoracic scoliosis.
      Echocardiogram showed a secundum ASD with bidirectional shunting and a
      ventricular septum bulging toward the left ventricle in diastole, and then toward
      the RV in systole causing obliteration of the RV. The peak pressure gradient
      measured across the RV outflow by continuous wave Doppler was 30 mmHg. Cardiac
      catheterization revealed an elevated RV pressure without pulmonary hypertension
      and confirmed the pressure gradient. Right ventriculography revealed the septal
      excursion toward the RV in systole, leaving only a small residual cavity in the
      inflow and outflow regions of the RV. The ASD was closed with an autologous
      pericardial patch. A thin, fibrous portion of the ventricular septum was resected
      and replaced with a Dacron patch. From the histological examination, the RV
      cavity obliteration turned out to be produced by the excursion of the infarcted
      ventricular septum.

PMID- 16636504
TI  - The HEARTSTRING proximal seal system is a possible source of atheroembolism.
AB  - It is necessary to use side clamps to construct proximal anastomoses in off-pump
      coronary artery bypass, and this can be related to neurologic complications.
      Recently a new device, the HEARTSTRING device, was developed. We present a 78
      year-old man who underwent emergent bypass surgery using the HEARTSTRING device
      to avoid a side clamp. We found atherosclerotic debris from the punched hole and,
      unfortunately, a postoperative neurological complication resulted. We strongly
      suggest that it is most important that potential candidates for the HEARTSTRING
      device be carefully selected to reduce possible neurologic complications. We
      report that while this new device is useful, there is a potential pitfall in
      using it; that it is a possible source of atheroembolism.

PMID- 16636505
TI  - Persistent left ventricular dysfunction in takotsubo cardiomyopathy after
      pacemaker implantation.
AB  - Two cases of takotsubo cardiomyopathy occurred after pacemaker implantation, both
      in elderly women who received a dual-chamber pacemaker for complete
      atrioventricular block. They had persistent left ventricular dysfunction even
      during their convalescence.

PMID- 16636506
TI  - Three-way bipolar forceps: a novel bipolar coagulator system for nerve
      stimulation and detection of nerve potentials.
AB  - Preoperative characterization of brain anatomy by magnetic resonance imaging and
      intraoperative functional characterization of the nervous system is essential in
      patients undergoing radical resection of brain tumors. A novel integrated system
      was developed combining conventional bipolar forceps with an electric stimulator
      and an oscilloscope. The system consists of a mechanical switching circuit
      allowing a wide range of electric characteristics and was designed to perform
      intraoperative electrophysiological studies, including functional mapping and
      measurements of motor evoked potentials (MEPs) and somatosensory evoked
      potentials (SEPs). This system achieved a significant reduction in exchange time
      (from 3.63+/-1.00 sec to 1.12+/-0.42 sec) between coagulation and stimulation,
      and reproducible measurement of MEPs from porcine limbs by cortical stimulation
      using the bipolar forceps. Functional mapping under awake craniotomy was carried
      out by cortical stimulation in patients with glioblastoma, and median nerve SEPs
      with high signal-to-noise ratio were elicited from the bipolar forceps on the
      sensory cortex of patients under general anesthesia. This integrated system is
      technically easy to operate and allows functional monitoring of an area that
      would otherwise be difficult to access using conventional methods. This three-way
      bipolar forceps system may reduce postoperative complications in patients
      undergoing neurosurgical procedures.

PMID- 16636507
TI  - Optimal extent of resection in vestibular schwannoma surgery: relationship to
      recurrence and facial nerve preservation.
AB  - Surgical treatment of vestibular schwannoma is targeted at complete removal with
      preserved neurological function. Complete removal may cause significant deficits,
      whereas subtotal tumor removal is associated with a high recurrence rate. The
      present study assessed the risk of tumor recurrence and postoperative facial
      nerve function in relation to the extent of surgical resection by reviewing the
      clinical records and radiological findings of 116 patients with vestibular
      schwannoma treated between 1990 and 1999. The extent of resection was classified
      as follows: gross total resection (GTR), near total resection (NTR), and subtotal
      resection (STR). Facial nerve function was graded using the modified House
      Brackmann grade, and patients grouped into good (grades 1-2) and intermediate or
      poor (grades 3-6). Of the 116 patients, 26 (22%) underwent GTR, 32 (28%) NTR, and
      58 (50%) STR. The recurrence rates were 3.8% (1/26 cases), 9.4% (3/32), and 27.6%
      (16/58) for GTR, NTR, and STR, respectively. GTR and NTR showed no statistically
      significant difference in terms of recurrence rate (p=0.620). However, recurrence
      was significantly less after NTR than STR (p=0.043). Immediately postoperative
      facial nerve function was good in 15.4% of patients after GTR, 40.6% after NTR,
      and 46.6% after STR. The STR and NTR carried a lower risk of facial nerve palsy
      than GTR in the immediately postoperative stage (p=0.006 and 0.036,
      respectively). Nevertheless, no statistical significance was observed in extent
      of resection and postoperative facial nerve outcome between the groups at last
      follow up (p=0.227). GTR is the ideal surgical treatment for vestibular
      schwannoma, but NTR is a good option, with better facial nerve function
      preservation than GTR without significantly increasing the risk of recurrence.

PMID- 16636508
TI  - Effectiveness of cerebral hemispherotomy for improving behavioral disorders
      associated with intractable post-traumatic seizures.
AB  - A 25-year-old man presented with intractable post-traumatic seizures after
      suffering cerebral contusion in a traffic accident at age 5 years. Cerebral
      hemispherotomy was performed to transect the neuronal fibers to interrupt
      connections between seizure foci in wide areas of the brain, and to minimize the
      resected brain parenchyma. His seizures resolved and behavioral disorders
      improved, which had been impaired since age 8 years. Increased glucose metabolism
      in the normal frontal lobe detected by interictal fluorodeoxyglucose-positron
      emission tomography was correlated with the improvements in behavioral disorders.
      These findings suggest that the effects of seizures may be reversible in brain
      areas connected with, but remote from, the epileptogenic cortex.

PMID- 16636509
TI  - Delayed hemorrhage from completely obliterated arteriovenous malformation after
      gamma knife radiosurgery.
AB  - A 43-year-old female was treated with gamma knife radiosurgery (GKS) for right
      frontal arteriovenous malformation (AVM) manifesting as absence seizures.
      Complete nidus obliteration was confirmed on angiography 4 years after GKS.
      However, she experienced recurrence of her previous seizures and delayed
      hemorrhage occurred within the treated nidus, despite absence of abnormalities by
      repeated angiography 81 months after GKS. She was treated conservatively and
      discharged home without neurological deficits. The risk of hemorrhage from
      obliterated AVM is significantly reduced but not eliminated after radiosurgery.
      Recanalization of thrombus that is too small to detect by neuroimaging may result
      in delayed hemorrhage.

PMID- 16636510
TI  - Resection of arteriovenous malformation in a patient with hemophilia type A.
AB  - A 34-year-old man with hemophilia type A presented with a huge intracerebral
      hematoma (ICH) in the left frontoparietal lobe due to rupture of an arteriovenous
      malformation (AVM). Angiography demonstrated the AVM in the frontoparietal lobe
      fed by the anterior cerebral arteries and the middle cerebral arteries, with a
      vein draining into the superior sagittal sinus. He developed signs of cerebral
      herniation due to the huge ICH. An emergent operation was performed to reduce
      intracranial pressure and to stop bleeding from the AVM under continuous
      administration of factor VIII. To prevent postoperative hemorrhage, aggressive
      blood pressure control and continuous administration of factor VIII were
      performed for 10 days. His neurological status improved so that he could hold a
      simple conversation. Continuous administration of factor VIII during surgery and
      intensive intra- and postoperative therapy resulted in a favorable outcome for
      this patient with hemophilia type A.

PMID- 16636511
TI  - Trigeminal neuralgia associated with an anomalous artery originating from the
      persistent primitive trigeminal artery.
AB  - A 31-year-old man presented with typical trigeminal neuralgia caused by an
      anomalous variant type of anterior inferior cerebellar artery (AICA) directly
      branching from the primitive trigeminal artery (PTA). Three-dimensional computed
      tomography angiography, magnetic resonance angiography, and magnetic resonance
      cisternography disclosed that this anomalous artery originated from the PTA and
      coursed to the AICA territory of the cerebellum. Microvascular decompression
      surgery disclosed the trigeminal nerve compressed by this AICA variant together
      with the superior cerebellar artery. These arteries were successfully
      transpositioned to decompress the nerve. Careful and thorough inspection around
      the trigeminal nerve verified that the PTA did not conflict with the nerve. This
      unusual case was caused by compression of the trigeminal nerve from the AICA
      directly originating from the PTA, without the more common involvement of the
      PTA.

PMID- 16636512
TI  - Isolated oculomotor nerve paresis in anaplastic astrocytoma with exophytic
      invasion.
AB  - A 30-year-old man presented with a supratentorial malignant glioma manifesting as
      isolated progressive left oculomotor nerve paresis. Computed tomography and
      magnetic resonance imaging showed an intra-axial tumor in the left temporal lobe,
      extending to the basal and prepontine cisterns, and compressing the brainstem.
      The tumor was removed subtotally. The histological diagnosis was anaplastic
      astrocytoma. Malignant glioma with exophytic growth in the temporal lobe should
      be considered in the differential diagnosis of isolated oculomotor nerve paresis.

PMID- 16636513
TI  - Atlas hypoplasia associated with non-traumatic retro-odontoid mass.
AB  - A 38-year-old man presented with progressive cervical myelopathy due to atlas
      hypoplasia associated with non-traumatic retro-odontoid mass. The neuroimaging
      findings suggested hypertrophy of the transverse ligament of the atlas. No
      histological confirmation of the retro-odontoid mass was obtained. Clinical
      manifestations improved after posterior decompression. Decompressive laminectomy
      of the atlas with or without fusion can achieve a good outcome in such cases.

PMID- 16636514
TI  - Temporal lobe epilepsy caused by dermoid cyst.
AB  - A 15-year-old boy presented with a dermoid cyst in the left temporal lobe
      manifesting as complex partial seizures. Magnetic resonance imaging demonstrated
      a tumor with mixed signal intensity in the left anterior temporal subdural area,
      but no evidence of rupture. Intraoperatively, the tumor was located mainly in the
      deep sylvian fissure, adjacent to the amygdala, and had compressed the
      hippocampus. Intraoperative electrocorticography (ECoG) showed sporadic
      interictal spikes in both the adjacent areas of the tumor and over the anterior
      segment of the hippocampus. Total removal of the tumor and gliotic area of the
      surrounding tissue including the amygdala was performed. The hippocampal
      epileptic region was treated by transection of the pyramidal layer to preserve
      verbal memory function. Histological examination showed the dermoid tumor was
      closely attached to the brain parenchyma. The complex partial seizures ceased
      completely after surgery. Intraoperative recording of ECoG from the hippocampus
      and other limbic structures was very important to determine the epileptogenic
      area even if the tumor did not directly invade the hippocampus.

PMID- 16636515
TI  - Dynamic computed tomography myelography for the investigation of cervical
      degenerative disease.
AB  - Dynamic computed tomography (CT) myelography was conducted in 15 patients with
      cervical degenerative disease to assess the lesions responsible for their
      symptoms. CT myelography was performed using a multi-detector row helical CT
      system in dynamic positions (flexion or extension or both) in addition to the
      neutral position. Fine sagittal reconstructed images could be obtained in
      addition to axial images. This method provided static information including
      cervical vertebral body deformities, and good contrast images of the spinal cord,
      nerve roots, and cerebrospinal fluid space. In addition, laterality of the
      offending lesion and changes exaggerated by cervical motion were clearly shown in
      both axial and sagittal images. Ten of 15 patients demonstrated dynamic changes
      including dynamic canal stenosis or spinal cord impingement. The operative
      strategies were changed based on dynamic CT myelography findings in three of the
      15 patients. Dynamic CT myelography can provide the axial and sagittal images
      required for flexion-extension studies, and in combination with conventional
      imaging modalities, provides valuable information for determining treatment
      strategies and objectives.

PMID- 16636516
TI  - Clinical features of cauda equina tumors requiring surgical treatment.
AB  - In this study, we evaluated the clinical features of cauda equina tumors
      requiring surgical treatment. Medical records of 28 patients with cauda equina
      tumors (13 men and 15 women) undergoing surgical treatment were retrospectively
      reviewed. The majority of histological diagnoses indicated schwannoma (23 cases,
      82%), and the remaining 5 indicated ependymoma, neurofibroma, meningioma, and
      ganglioneuroblastoma. In 86% of the cases, the initial symptom was pain in the
      lower back and/or lower extremities. Preoperatively, half of the patients had
      symmetrical pain in the lower back or lower extremities, severe pain in the
      supine position, or pain that was increased by coughing. One third of the
      patients needed morphine to control nocturnal pain. Tumor size, as determined by
      magnetic resonance imaging (MRI), correlated with preoperative symptom duration
      (r = 0.66, p < 0.001). These findings indicate that symmetrical lower back pain
      and/or pain that radiates to both lower extremities and increases in the supine
      position are characteristic of cauda equina tumors. The correlation between
      symptom duration and tumor size indicates that earlier diagnosis of this tumor is
      necessary. Earlier diagnosis based on these characteristic symptoms should make
      use of further examinations such as MRI.

PMID- 16636517
TI  - Losartan, an angiotensin-II receptor antagonist, retards the progression of
      advanced renal insufficiency.
AB  - Chronic renal disease with elevated level of serum creatinine (Cr) often
      progresses to end-stage renal disease. Although blockade of the renin-angiotensin
      system has been shown to slow the progression of chronic renal disease, it
      remains uncertain whether one could expect such a renoprotective effect even when
      the treatment is initiated late in the course of renal disease. The purpose of
      the present study was to examine the effect of losartan, an angiotensin-II
      receptor antagonist, on the progression of advanced renal insufficiency. We
      retrospectively analyzed eight hypertensive patients, whose baseline Cr levels
      exceeded 2.0 mg/dl (2.2-5.5); the subjects included 6 non-diabetic glomerular
      diseases, 1 diabetic nephropathy and 1 polycystic kidney disease. Losartan was
      given at the dosage of 25-50 mg/day. Changes in mean blood pressure (MBP) and
      serum levels of Cr, potassium (K) and uric acid were evaluated after treatment
      for 24 weeks. Slopes of reciprocal of serum Cr plotted against time (1/sCr
      slope), which indicate the rate of renal function loss before and after the
      treatment period, were compared. There was a significant reduction of 1/sCr slope
      after losartan (-0.004 +/- 0.002 dl/mg/week before and -0.001 +/- 0.002
      dl/mg/week after the treatment, p < 0.05). MBP and serum levels of Cr, K and uric
      acid were not changed significantly by losartan treatment. However, improvement
      of 1/sCr slope was correlated to the degree of MBP changes. Based on the
      available data from 4 patients, proteinuria was decreased in 3 patients. These
      results suggest that losartan may retard the progression of advanced renal
      insufficiency.

PMID- 16636518
TI  - Impact of type A behavior on brachial-ankle pulse wave velocity in Japanese.
AB  - Pulse wave velocity (PWV) is the velocity of a pulse wave traveling a given
      distance between 2 sites in the arterial system, and is a well-known indicator of
      arteriosclerosis. Brachial-ankle PWV (baPWV) is a parameter more simple to
      obtain, compared with the conventional PWV, and is an easy and effective means of
      evaluating arteriosclerosis. BaPWV can be obtained by only wrapping the four
      extremities with blood pressure cuffs, and it can be easily used to screen a
      large number of subjects. Type A behavior has been confirmed as an independent
      risk factor for the development of coronary heart disease. To examine the
      relationship between Type A behavior and arteriosclerosis, 307 normal Japanese
      subjects were classified into either a Type A group (n = 90) or a non-Type A
      group (n = 217) by using Maeda's Type A Scale. BaPWV was evaluated using a PWV
      diagnosis device. The baPWV in the Type A group was significantly higher than
      that obtained in the non-Type A group. The baPWV showed a positive correlation
      with age both in the Type A group and in the non-Type A group; however, the
      straight-line regression slope of baPWV versus age in the Type A group was
      significantly larger than that in the non-Type A group. Therefore, our results
      suggest that arteriosclerosis might be promoted earlier in subjects expressing
      the Type A behavior pattern. Type A behavior pattern is confirmed as a risk
      factor for arteriosclerosis, and may increase the risk of the cardiovascular
      disease related to arteriosclerosis.

PMID- 16636519
TI  - Encapsulation cell therapy for mucopolysaccharidosis type VII using genetically
      engineered immortalized human amniotic epithelial cells.
AB  - Mucopolysaccharidosis type VII (MPSVII) is a lysosomal storage disease resulted
      from a deficiency of the enzyme beta-glucuronidase (GUSB), which is necessary for
      degradation of glycosaminoglycans (GAGs). The deficiency of GUSB causes
      progressive accumulation of GAGs and subsequent lysosomal distension in multiple
      tissues, including the central nervous system (CNS). In murine experiments, bone
      marrow transplant, enzyme replacement, viral vectors, and genetically modified
      cells were successfully used for correction of the visceral accumulation of GAGs,
      but little improvement was seen in the brain, because these therapeutic agents
      cannot cross the blood-brain barrier (BBB). Although direct intracerebral
      injection of GUSB-encoding viral vectors has been developed to bypass the BBB,
      the possibility of tumor formation and the toxicity of over-expressed GUSB have
      been reported. In this study, we generated immortalized human amniotic epithelial
      (IHAE) cells to maintain the effect of implantation, and encapsulated these cells
      to prevent harmful immunological response and tumor formation and to regulate the
      level of GUSB expression within the host. Moreover, we generated IHAE cells that
      over-express and secrete human GUSB following transduction with an adenoviral
      vector encoding human GUSB. Therapeutic efficacy for MPSVII was evaluated in and
      ex vivo experiments using these encapsulated genetically engineered GUSB-encoding
      IHAE cells. We confirmed that encapsulated genetically engineered IHAE cells
      could secrete significant amounts of GUSB outside the capsule in vitro and into
      the cerebral parenchyma of C3H mice seven days after the capsule implantation.
      Thus, encapsulation cell therapy using genetically engineered IHAE cells is an
      effective armamentarium for the treatment of MPSVII.

PMID- 16636520
TI  - Improvement in knee extension strength through training by means of combined
      electrical stimulation and voluntary muscle contraction.
AB  - Weight training (WT) is the most common method of maintaining and increasing
      muscle strength. WT, however, is not always useful as it requires the external
      resistance and stabilization. We have developed a "hybrid training" (HYB)
      approach that avoids these problems by using electrically stimulated muscles to
      provide resistance to the motion of a muscle undergoing training. Here we report
      the efficacy of HYB compared with conventional WT for increasing the muscle
      strength around the knee at both slow and fast joint speeds (at 30 and 180
      degrees /sec). Two matched groups, each of 8 healthy men aged 22 years, exercised
      3 times/week for six weeks. Both groups showed significantly increased strength
      in concentric torque at 30 degrees /sec (HYB +28%, WT +33%) and at 180 degrees
      /sec (HYB +33%, WT +38%), and also in eccentric torque at 30 degrees /sec (HYB
      +25%, WT +24%) and at 180 degrees /sec (HYB +19%, WT +30%) (p < 0.001). HYB is
      comparable with WT exercising with the exception of high-speed contractions,
      while HYB has a clear advantage in not needing external resistance equipment or
      stabilization. HYB is therefore considered a useful approach for strengthening
      muscles when a person is restricted to bed rest or during space flight.

PMID- 16636521
TI  - Slow coronary flow is associated with carotid artery dilatation.
AB  - Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized
      clinical entity, but its etiopathogenesis remains unclear. Carotid intima-media
      thickness (CIMT) is a noninvasive marker of atherosclerosis. The aim of this
      study was to investigate the CIMT and diameter of carotid and coronary artery in
      relation to SCF. Twenty-four patients with angiographically diagnosed SCF (51 +/-
      7 years), and 26 age-matched subjects with normal coronary flow (NCF) (52 +/- 8
      years) in the coronary angiography were enrolled. Coronary flow rates were
      documented by thrombolysis in myocardial infarction (TIMI) frame count (TFC), a
      simple method for evaluating coronary blood flow. Carotid and coronary artery
      diameters and CIMT were measured. Mean TFC was significantly higher in patients
      with SCF than in patients with NCF (p < 0.001). There were no significant
      differences regarding maximum (p = 0.84) and mean CIMT (p = 0.61). On the other
      hand, carotid lumen (p = 0.03) and coronary artery diameters (p = 0.001) were
      significantly greater in patients with SCF than in subjects with NCF. There was a
      significant relation between mean coronary artery diameter and TFC (p = 0.004,
      95% CI for OR: 1.61-11.87). In conclusion, these findings suggest that CIMT is
      not altered in patients with SCF as compared with those with NCF. However,
      carotid and coronary artery diameters are increased in patients with SCF as
      compared to those with NCF. Because the common carotid artery can be assessed in
      nearly every patient, carotid artery dilatation may be used as an early indicator
      for SCF.

PMID- 16636522
TI  - A case of normal tension glaucoma associated with Buerger's disease.
AB  - Open angle glaucoma, a slowly progressive optic atrophy, is clinically
      characterized by visual field defects corresponding to excavation of the optic
      disc, called glaucomatous cupping. Open angle glaucoma is further divided into
      primary open angle glaucoma caused by elevated intraocular pressure (higher than
      the normal limit of 21 mmHg), and normal tension glaucoma, in which intraocular
      pressure is in the normal range. Here we report a case of normal tension glaucoma
      associated with Buerger's disease, also known as thromboangiitis obliterans,
      which causes systemic blood flow disturbance. A 66-year-old man suffering from
      Buerger's disease for 10 years was diagnosed as having branch retinal artery
      occlusion in his left eye. He was referred to our clinic due to progressive
      visual field disturbance in that eye. Ophthalmologic examinations revealed
      occlusion in the infero-temporal retinal artery in the left eye, and glaucomatous
      cupping, normal intraocular pressure, retinal vessel tortuosity and retinal
      arteriosclerosis in both eyes. Visual field examination revealed decreased
      retinal sensitivities in the areas within the visual field arches above and below
      fixation from the blind spot to the median raphe, corresponding to the arcuate
      retinal nerve fibers comprising the Bjerrum areas and the area corresponding to
      the retinal artery occlusion. Buerger's disease is characterized by the
      development of segmental thrombotic occlusions and vasospasm of the medium and
      small arteries. Our case suggests that the blood flow disturbance due to
      arteriosclerosis, thrombotic occlusions and vasospasm associated with Buerger's
      disease might affect the ophthalmic circulation system, thereby contributing to
      the etiology of normal tension glaucoma.

PMID- 16636523
TI  - A classic adamantinoma arising from osteofibrous dysplasia-like adamantinoma in
      the lower leg: a case report and review of the literature.
AB  - Adamantinoma is known as a low-grade malignant biphasic tumor. Classic
      adamantinoma is in general characterized by admixture of both epithelial and
      osteofibrous components that are associated with various proportions and
      differentiation patterns. Osteofibrous dysplasia (OFD) is a self-limited benign
      fibro-osseous lesion of bone during infancy and childhood. OFD-like adamantinoma
      is characterized by predominance of osteofibrous tissues, in which small groups
      of epithelial cells are only detected by careful search or immunohistochemistry.
      There have been controversies as to the potential correlation among OFD, OFD-like
      adamantinoma and classic adamantinoma. We report an unusual case of adamantinoma
      arising in the tibia, with an extensive review of the literature. The present
      findings suggest a direct correlation between OFD-like adamantinoma and classic
      adamantinoma. At the age of 12 years, the tibial biopsy lesion was diagnosed as
      OFD. At the age of 23, the lesion became larger and more destructive on x-ray
      films. The biopsy lesion was diagnosed as classic adamantinoma. Wide excision was
      performed. The primary lesion was retrospectively diagnosed as OFD-like
      adamantinoma because of presence of keratin-positive epithelial cells within the
      stroma. At five years after surgery, the patient was free from recurrence or
      metastasis. The retrospective histological findings of OFD-like adamantinoma in
      the original biopsy and of a classic adamantinoma in all sections of the later
      resection specimen raised the possibility of an unusual progression of OFD-like
      adamantinoma to a classic adamantinoma. The present case and the literature
      review suggest that an OFD-like adamantinoma may be a precursor lesion of classic
      adamantinoma. Therefore, the possibility of progression of OFD-like adamantinoma
      to a classic adamantinoma should be kept in mind, particularly when the
      destructive changes are seen radiologically.

PMID- 16636524
TI  - Successful autologous peripheral blood stem cell transplantation using thiotepa
      in a patient with systemic sclerosis and cardiac involvement.
AB  - A 19-year-old man with systemic sclerosis (SSc) was hospitalized for autologous
      peripheral blood stem cell transplantation (auto-PBSCT) due to progressive
      scleroderma and cardiac involvement despite conventional treatment. During the
      administration of cyclophosphamide (60 mg/kg/day for 2 days) for mobilization and
      collection of CD34+ selected peripheral blood stem cells, he developed congestive
      heart failure. Echocardiogram showed hypokinetic asynergy from the septum to
      posterior wall, which might indicate underlying cardiac damage. We were also
      concerned about the risk of high-dose cyclophosphamide-induced cardiotoxicity.
      Since the dose-limiting toxicity of thiotepa, an alkylating agent, is
      myelosuppression, and cardiac toxicity due to thiotepa is less common, we used a
      conditioning regimen consisting of thiotepa (10 mg/kg/day, day -5) and low-dose
      cyclophosphamide (50 mg/kg/day, days -3 and -2), instead of the conventional high
      dose cyclophosphamide (50 mg/kg/day x 4 days/course). The post-transplant course
      was uneventful, and the modified Rodnan skin thickness score improved from 32 to
      15. The present case report demonstrates that thiotepa can be employed as a
      conditioning regimen for auto-PBSCT in SSc patients with cardiac involvement in
      order to reduce cyclophosphamide-induced cardiotoxicity.

PMID- 16636525
TI  - Pulse methylprednisolone therapy in type 3 adenovirus pneumonia with
      hypercytokinemia.
AB  - Adenovirus pneumonia is uncommon but its severe infection has a mortality as high
      as 10%, and survivors may have residual airway damages, manifested by
      bronchiectasis, bronchiolitis obliterans, or pulmonary fibrosis. We report a case
      of adenovirus pneumonia demonstrating fatal respiratory distress. Adenovirus was
      isolated from pharyngeal specimens using cell culture and typed as serotype 3 by
      a combination of polymerase chain reaction (PCR) and restriction fragment length
      polymorphism analysis. The patient characteristically showed hypercytokinemia,
      characterized by increased levels of lactate dehydrogenase, ferritin, and several
      cytokines including interferon-gamma and interleukin-6. We treated the patient
      with pulse methylprednisolne therapy (25 mg/kg/day, for 3 days), resulting in the
      rapid amelioration of respiratory distress. This is the first report describing
      the treatment of pulse methylprednisolone therapy in fatal adenovirus pneumonia.
      During the clinical course, serum Krebs von den Lungen-6 (KL-6), which is a
      marker for the activity of diffuse interstitial lung disease, was elevated,
      suggesting that serum KL-6 could be available as a marker of pulmonary prognosis
      in viral pneumonia.

PMID- 16636526
TI  - Necrotizing granulomata in the lung preceding colonic involvement in 2 patients
      with Crohn's disease.
AB  - Extraintestinal involvement, including the chest, is common in the late course of
      Crohn's disease. We describe 2 female patients in whom the course of the disease
      was unique in two aspects: (1) each had a pulmonary mass with granulomatous
      inflammation and necrosis, and (2) these findings had preceded the colonic
      involvement by 5 years. This sequence supports some of the theories on the
      pathogenesis of Crohn's disease and on its possible relation with sarcoidosis,
      another idiopathic granulomatous disease.

PMID- 16636527
TI  - Comparison of clinical characteristics and outcomes of patients with COPD
      exacerbation with or without venous thromboembolism.
AB  - BACKGROUND: Although some studies evaluated venous thromboembolism (VTE)
      prevalence in patients with chronic obstructive pulmonary disease (COPD), they
      contain no detailed description of the patients' characteristics. OBJECTIVES: It
      was the aim of this study to investigate the frequency and clinical
      characteristics and outcomes of VTE in patients with COPD exacerbation. METHODS:
      Between October 2004 and February 2005, 120 consecutive patients were included in
      the study. On admission, Doppler examination of lower extremities in all cases
      and spiral computed tomography of the thorax in cases with a suspicion of
      pulmonary thromboembolism were performed. A questionnaire was used to take a
      detailed history. In addition to routine laboratory tests, chest X-ray,
      postbronchodilator spirometry, arterial blood gas analysis and serum levels of D
      dimer and C-reactive protein were evaluated, as well as dyspnea score and
      performance status before exacerbation. The hospitalization durations and
      mechanical ventilation requirements were also recorded. RESULTS: VTE was
      determined in 16 cases (13.3%). In patients with VTE, the travel history was
      higher (p < 0.001), the dyspnea score worse (p = 0.005), the duration of
      hospitalization longer (p < 0.001) and the mechanical ventilation requirement
      increased (p < 0.001); a change in mental status was highly associated with the
      presence of VTE (p < 0.001). CONCLUSIONS: It seems that VTE occurrence was higher
      in the presence of a risk factor causing immobility such as travel history and
      increased dyspnea. The cases with severe disease are more likely to have VTE.
      Preventive measures may be considered in such patients because their
      hospitalization stay and mechanical ventilation requirement are increased.

PMID- 16636528
TI  - Repeated pulmonary rehabilitation in severe and disabled COPD patients.
AB  - BACKGROUND: The optimal frequency of delivering a pulmonary rehabilitation
      program (PR) is not yet a well established issue. It is still unclear whether
      repeated PR at established intervals will result in effective maintenance or
      further improvement in the patient's health status. OBJECTIVES: To investigate
      whether more frequently repeated PR in patients with COPD (1) leads to similar
      short and long-term physiological gains, and (2) decreases the burden due to
      hospitalization. METHODS: Thirty-five disabled COPD patients (FEV(1) below 50%
      predicted, MRC score 3) in a stable state were studied in a randomized controlled
      trial. After completing an initial inpatient PR program, they were randomly
      assigned to either group 1 (performing a second and a third PR after 6 and 12
      months) or group 2 (performing only a second PR after 12 months). RESULTS: Lung
      functions, exercise capacity (by means of a timed walk test - 6MWT), peak-effort
      dyspnea (D) and leg fatigue (F), and health-related quality of life by means of
      SGRQ were assessed prior to (T1, T3, T5) and after (T2, T4, T6) each PR program:
      the same measures were taken on an outpatient basis at T3 in group 2. The number
      of hospital admissions (HA) and days spent in the hospital (DH) were also
      recorded over the year. The two groups did not differ in any parameter at
      baseline. 6MWD, D, F and SGRQ improved to the same level (p = 0.05) after each PR
      in both groups. However, the baseline level of D, F and SGRQ symptoms and impact
      scores progressively improved over time in group 1 but not in group 2. After 12
      months, a larger amount of patients in Group 1, as compared to Group 2, reported
      H10 DH/year (p < 0.0001). CONCLUSIONS: In severe and disabled COPD, a more
      frequently repeated inpatient PR may lead to some additional physiological and
      clinical benefits over 1 year.

PMID- 16636529
TI  - Endobronchial embolization with a silicone spigot as a temporary treatment for
      massive hemoptysis: a new bronchoscopic approach of the disease.
AB  - A 39-year-old-woman was treated successfully by a combination of endobronchial
      and bronchial artery embolization for massive hemorrhage originating from the
      posterior segment of the right upper lobe. Endobronchial embolization was
      performed using a silicone spigot placed via flexible bronchoscopy in order to
      prevent alveolar inundation preceding and during the time of bronchial artery
      embolization. Massive hemorrhage is a rare and severe condition associated with a
      high mortality that requires rapid intervention and management. We describe a
      case that emphasizes the efficacy of a multidisciplinary approach including the
      use of a new bronchoscopic technique.

PMID- 16636530
TI  - Linear pulmonary opacities in an asymptomatic patient.

PMID- 16636531
TI  - Darbepoetin alfa administered every other week maintains hemoglobin levels over
      52 weeks in patients with chronic kidney disease converting from once-weekly
      recombinant human erythropoietin: results from simplify the treatment of anemia
      with Aranesp (STAAR).
AB  - BACKGROUND/AIM: Darbepoetin alfa, an effective treatment for anemia of chronic
      kidney disease (CKD), can be administered at extended intervals. Simplify the
      Treatment of Anemia with Aranesp (STAAR), a multicenter, 52-week study, was
      conducted to assess the efficacy of darbepoetin alfa administered subcutaneously
      every other week (Q2W) in maintaining hemoglobin (Hb) in CKD patients not
      receiving dialysis. METHODS: This is a subgroup analysis of subjects converted
      from once-weekly (QW) recombinant human erythropoietin (rHuEPO; US Aranesp
      package insert) and who received up to 52 weeks of darbepoetin alfa therapy
      (evaluation period 20-32 weeks). Enrolled subjects had a creatinine clearance <
      or = 70 ml/min or an estimated glomerular filtration rate < or = 60 ml/min and
      transferrin saturation > or = 20%. Darbepoetin alfa doses were titrated to
      maintain Hb levels < or = 12 g/dl. The primary endpoint was mean Hb during
      evaluation. RESULTS: There were 524 subjects enrolled in the study who were
      previously receiving rHuEPO QW. Mean Hb +/- standard deviation was 11.2 +/- 1.27
      g/dl at baseline, and the least squares mean +/- SE was 11.4 +/- 0.04 during
      evaluation. The mean +/- SD Q2W darbepoetin alfa dose was 49.7 +/- 21.9 microg at
      baseline and 48.9 +/- 35.5 microg at evaluation. Darbepoetin alfa was well
      tolerated. CONCLUSIONS: Study subjects with CKD receiving QW rHuEPO were
      effectively converted to Q2W darbepoetin alfa, which was well tolerated. Hb
      levels were maintained over 52 weeks without a significant change in darbepoetin
      alfa dose.

PMID- 16636532
TI  - The effect of human growth hormone on superoxide dismutase activity, glutathione
      and malondialdehyde levels of hypoxic-ischemic newborn rat brain.
AB  - OBJECTIVES: We investigated the effect of human growth hormone (GH) on newborn
      rat brain superoxide dismutase, glutathione and malondialdehyde (MDA) levels in
      hypoxic-ischemic (H-I) newborn rats. METHODS: Fourty-eight 7 days old newborn
      rats were randomized to a healthy (n: 15), H-I (n: 18) and GH administered H-I
      (GH-H-I, n: 15) group. Permanent, left common carotid ligation was performed in
      the H-I groups. In the GH-H-I group, 50 mg/kg human GH (Norditropin Simplex, Novo
      Nordisk A/S) was administered subcutaneously just before carotid artery ligation.
      Two hours after ligation, rats were subjected to 2 h of hypoxemia and then were
      decapitated. Right and left cerebral hemispheres (CHs) and cerebellum-brain stem
      (C-BS) were separated. RESULTS: Glutathione levels of each region were not
      statistically different from each other in and between the groups. Superoxide
      dismutase levels were higher in C-BSs compared to CHs (for each comparison p <
      0.01). CHs and C-BS MDA levels were similar in the control and H-I groups but MDA
      levels of both CHs of the GH-H-I group were significantly higher than the levels
      of the H-I group (p = 0.01; p = 0.024, respectively). Left CH MDA level of GH-H-I
      group was higher compared to left CH MDA of the control group (p = 0.045) while
      there was no difference between right CHs. In the GH-H-I group, left CH MDA level
      was higher than the C-BS (p = 0.03). MDA levels of the C-BSs did not differ
      between the groups (p > 0.05). CONCLUSION: Although we have not evaluated the
      effect of GH histopathologically, increased lipid peroxidation especially in the
      H-I (left) hemisphere of the GH treated rats might suggest that GH treatment may
      be harmful in H-I encephalopathy.

PMID- 16636534
TI  - Outcome of extremely preterm infants randomized at birth to different PaCO2
      targets during the first seven days of life.
AB  - BACKGROUND: Ventilation with higher PaCO(2) goals may reduce lung injury and
      bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher
      PaCO(2) goal than in previous trials. OBJECTIVE: To determine the clinical
      benefits and safety of higher PaCO(2) goals for ventilated preterm infants. STUDY
      DESIGN: Preterm infants with a gestational age between 23 and 28 completed weeks
      receiving mechanical ventilation within 6 h of birth were randomized to be
      managed with either a PaCO(2) target between 55 and 65 mm Hg (7.3- 8.7 kPa,
      minimal ventilation) or 35 and 45 mm Hg (4.7- 6.0 kPa, routine ventilation) for
      the first 7 days of life. The primary outcome measure was BPD, defined as need
      for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age,
      or death. The neurodevelopmental status was assessed at 18-22 months corrected
      age. RESULTS: The trial was stopped early after enrolling 31% of the projected
      sample size. Enrolled infants had a median birth weight of 640 g. BPD or death
      occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants
      after routine ventilation. Minimal ventilation was associated with trends towards
      higher mortality and higher incidence of neurodevelopmental impairment, and a
      significantly increased combined outcome of mental impairment or death (p <
      0.05). CONCLUSION: Minimal ventilation as performed in this study did not improve
      clinical outcome, and may have been associated with a worse neurodevelopmental
      outcome.

PMID- 16636535
TI  - Stopping a randomized trial early: from protocol to publication. Commentary to
      Thome at al.: outcome of extremely preterm infants randomized at birth to
      different PaCO2 targets during the first seven days of life (Biol Neonate
      2006;90:218-225).

PMID- 16636536
TI  - Activity of the essential oil from Chenopodium ambrosioides grown in Cuba against
      Leishmania amazonensis.
AB  - BACKGROUND AND METHODS: Current therapy against leishmaniasis is unsatisfactory.
      Efficacious and safe new drugs are needed. In this study, we show the
      leishmanicidal effect of an essential oil from Chenopodium ambrosioides against
      Leishmania amazonensis. RESULTS: The tested product had a potent inhibitory
      action against promastigote and amastigote forms, with 50% effective dose values
      of 3.7 and 4.6 microg/ml, respectively. The essential oil showed a moderate
      toxicity on macrophages from BALB/c mice. An optimal dose of 30 mg/kg/day was
      effective when administered during 15 days by intraperitoneal route to BALB/c
      mice infected experimentally. CONCLUSION: These studies revealed a potential
      source for the discovery of novel drugs to combat the leishmaniasis based on the
      traditional medicine.

PMID- 16636537
TI  - Docetaxel pharmacokinetics with pre- and post-dialysis administration in a
      hemodyalized patient.
AB  - BACKGROUND: Docetaxel has a proven significant activity against breast, non-small
      cell lung, ovarian, head and neck, and hormone refractory prostate cancer.
      Preclinical pharmacokinetic studies have shown that hepatobiliary extraction is
      the major route of elimination. We conducted this study to elucidate the
      feasibility and safety of the use of docetaxel in hemodialysis patients. PATIENT
      AND METHODS: In a 72-year-old hormone refractory prostate cancer patient on
      hemodialysis for diabetic nephropathy for 3 years, a first dose (35 mg/m(2) iv)
      of docetaxel was completed 30 min before starting dialysis, while a second dose
      was administered 30 min after completion of a different hemodialysis session.
      Pharmacokinetic analysis was performed following both infusions. RESULTS: No
      apparent differences could be seen in the plasma concentration-time curves of
      docetaxel administered before or after dialysis. The patient experienced no
      significant toxicity after either administration of docetaxel. CONCLUSIONS:
      Docetaxel is safe in dialysis patients and does not require dose reduction.
      Dialysis does not remove this drug from blood.

PMID- 16636538
TI  - Dose-dependent therapeutic antiinfectives from ethnomedicines of bay islands.
AB  - BACKGROUND: The methanol extract of Ophirrhiza nicobarica, Alstonia macrophylla
      and Mallotus peltatus, ethnomedicines of Little Andaman, were investigated for
      antiinfective, antiinflammatory and antioxidant activities. METHODS: Toxicity was
      determined in cells and in an animal model. Antiviral, antibacterial and
      antifungal activity was determined by plaque reduction, disc diffusion and agar
      dilution methods. The antiinflammatory and antioxidant activities were also
      studied. RESULTS: O. nicobarica at 300 microg ml(-1) showed anti-HSV activity
      while M. peltatus and A. macrophylla showed antibacterial activity at 64-1,000
      microg ml(-1). Both extracts showed significant dose-dependent antiinflammatory
      and antioxidant activity at nontoxic concentrations. CONCLUSION: The alkaloid,
      flavonoid and beta-sitosterol isolated from bioactive parts had a dose-dependent
      therapeutic efficacy, justifying their use. Further study is required to know the
      mechanism of action.

PMID- 16636539
TI  - Antibacterial non-glycosidase activity of invertebrate destabilase-lysozyme and
      of its helical amphipathic peptides.
AB  - BACKGROUND: Since bactericidal properties of some lysozymes are independent of
      their glycosidase activity, we have investigated this phenomenon for destabilase
      lysozyme (DL) from medicinal leech (Hirudo medicinalis). METHODS: Glycosidase
      activity was determined on Micrococcus luteus, non-enzymatic antibacterial
      activity of heat-treated DL and of synthetic peptides alpha1, alpha2 and alpha3
      (fragments of its primary structure) on M. luteus, Escherichia coli, Bacillus
      brevis and Streptomyces chrysomallus. RESULTS: Glycosidase activity disappeared
      after the heating of native DL at 100 degrees C for 40 min. Antibacterial
      activity of heat-treated DL for M. luteus MDMSU128 and MDMSU140 expressed as
      minimal inhibitory concentration was 9.8.10(-8) and 12.10(-8) M, respectively,
      and to E. coli MDMSU52 11.10(-8) M. Antibacterial activity of synthetic peptide
      alpha1 for M. luteus MDMSU128 and for E. coli MDMSU52 was 8.3.10(-5) and 4.9.10(
      5) M, respectively. CONCLUSION: DL is the first invertebrate lysozyme with
      combined enzymatic and non-enzymatic antibacterial action.

PMID- 16636540
TI  - N-terminal pro-B-type natriuretic peptide in risk stratification after acute
      myocardial infarction in patients on long-term beta-adrenergic receptor blocker
      therapy.
AB  - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) appears to be a
      strong risk marker of mortality in patients with acute coronary syndrome.
      However, little information is available on NT-proBNP as a predictor of long-term
      serious cardiovascular events beyond that of left ventricular ejection fraction
      in patients with acute myocardial infarction (AMI), most of them treated with an
      early invasive strategy and on a uniform optimal secondary preventive medication
      including long-term beta-adrenergic receptor blockade. OBJECTIVE: To assess the
      prognostic impact of plasma NT-proBNP in patients with AMI who received optimal
      medical treatment including long-term beta-adrenergic receptor blockade. METHODS:
      Plasma NT-proBNP was measured in 219 patients (age range 31-80 years) with AMI at
      baseline, and then followed for a median duration of 1.63 years. The first
      occurrences of a serious cardiovascular event including cardiac mortality,
      nonfatal MI, and congestive heart failure were registered. RESULTS: Ninety
      serious cardiovascular events occurred. Left ventricular ejection fraction and
      reperfusion therapy with thrombolysis or percutaneous coronary intervention were
      identified as confounders. When adjusting for these factors in multivariate
      analysis, NT-proBNP was a strong predictor of serious cardiovascular events in
      patients with a plasma NT-proBNP of >162.2 pmol/l and aged <60 years (p = 0.001).
      The incidence rate was related to increasing NT-proBNP (p = 0.0017). The risk of
      serious cardiovascular events was higher in patients with NT-proBNP levels in the
      highest quartile (> or =162.2 pmol/l) than in those with levels in the three
      lowest quartiles (rate ratio = 2.5, 95% confidence interval = 1.6-3.9, p =
      0.0001). CONCLUSION: AMI patients with high plasma NT-proBNP seem to be at an
      increased risk of serious cardiovascular events, but only those < or =60 years of
      age.

PMID- 16636541
TI  - Bisoprolol improves echocardiographic parameters of left ventricular diastolic
      function in patients with systemic hypertension.
AB  - Left ventricular (LV) diastolic dysfunction (LVD) is a common complication
      secondary to hypertension. It has been reported that bisoprolol is effective in
      reducing blood pressure and has beneficial cardiac effects in patients with
      hypertension. However, its effect on LV diastolic function has not been studied
      in detail. In this study, we sought to determine bisoprolol's effect on left
      ventricle diastolic function. Data from 25 patients were statistically analyzed.
      Peaks E and A wave, E/A ratio, isovolumetric relaxation time and E wave
      deceleration time were measured echocardiographically. Doppler echocardiography
      measurements after bisoprolol treatment revealed an improvement in LV diastolic
      function. In conclusion, our results show that treatment with bisoprolol,
      improves echocardiographic parameters of LV diastolic function after 3 months of
      treatment.

PMID- 16636542
TI  - The relationship between plasma BNP level and the myocardial
      phosphocreatine/adenosine triphosphate ratio determined by phosphorus-31 magnetic
      resonance spectroscopy in patients with dilated cardiomyopathy.
AB  - The purpose of this study was to evaluate the correlation between the plasma B
      type natriuretic peptide (BNP) level and the myocardial phosphocreatine/adenosine
      triphosphate ratio determined using rapid phosphorus-31 magnetic resonance
      spectroscopy (31P-MRS) in patients with dilated cardiomyopathy (DCM). Thirteen
      DCM patients, who had slight or moderate heart failure, were examined. The plasma
      BNP was measured on a day close to the rapid 31P-MRS study. 31P-MRS measurements
      were conducted with a 1.5-T MR instrument. The plasma BNP levels tended to be
      correlated negatively with the myocardial phosphocreatine/adenosine triphosphate,
      although the correlation did not reach statistical significance (r = -0.54, p =
      0.06). By contrast, the log of the plasma BNP levels was correlated negatively
      with the myocardial phosphocreatine/adenosine triphosphate (r = -0.73, p < 0.01).
      Our results indicate that the myocardial energy metabolism evaluated using 31P
      MRS tends to be correlated with the severity of heart failure and left
      ventricular dysfunction estimated using the plasma BNP levels in DCM patients.
      This paper provides additional information regarding the relationship between the
      BNP and myocardial energy metabolism in DCM patients.

PMID- 16636543
TI  - Which factors are associated with the application of reperfusion therapy in ST
      elevation acute coronary syndromes?. Lessons from the Euro Heart Survey on Acute
      Coronary Syndromes I.
AB  - BACKGROUND/AIMS: A large proportion of patients with a ST-elevation acute
      coronary syndrome do not receive reperfusion therapy. In order to contribute to a
      better understanding of the clinical decision making process, we analyzed which
      factors are associated with the application of reperfusion therapy. METHODS: From
      the Euro Heart Survey of Acute Coronary Syndromes I, 4,260 patients with ST
      elevation acute coronary syndrome were selected for the current analysis, of
      which 1,539 (36%) patients received fibrinolysis and 904 (21%) primary
      percutaneous coronary intervention (PCI). The analysis contained 32 variables on
      demographics, medical history, admission parameters and reperfusion therapy.
      RESULTS: A short pre-hospital delay, arrival in a hospital with PCI facilities,
      severe ST-elevation, and participation in a clinical trial were the strongest
      predictors for receiving reperfusion therapy. Primary PCI was more likely to be
      performed than fibrinolysis in patients with a long pre-hospital delay, arriving
      in a hospital with PCI facilities, not participating in a clinical trial, and
      with at least one previous PCI. CONCLUSION: Hospital facilities and culture, pre
      hospital delay and infarction size play a major role in management decisions
      regarding reperfusion therapy in ST-elevation acute coronary syndrome. This
      analysis indicates which factors require special attention when implementing and
      reviewing the reperfusion guidelines.

PMID- 16636544
TI  - The anti-ischemic effect of metoprolol in patients with chronic angina pectoris
      is gender-specific.
AB  - Several gender-specific differences in cardiovascular diseases are known and
      pharmacokinetics of beta-blockers shows relevant sex-specific differences. The
      plasma levels of metoprolol, for example, are higher in women compared to men.
      However, randomized studies have shown that metoprolol has little or no greater
      reduction in the mortality of women following myocardial infarction. We tested
      the hypothesis that metoprolol might have significant gender-specific effects in
      patients with chronic angina pectoris. Body weight of women was slightly (-9%)
      less than that of men and the daily dose of metoprolol was similar in both
      groups. Thus, according to pharmacokinetics women should have obtained higher
      plasma levels of this drug and the ensuing pharmacologic effects of metoprolol
      should have been greater. Our results do not confirm this assumption. Metoprolol
      reduced the frequency of angina episodes and the consumption of nitroglycerin
      tablets to a similar extent in both sexes. However, the pretreatment hemodynamic
      profiles confirmed the existence of gender-specific differences: women had
      significantly higher heart rate and blood pressure both at rest and during
      exercise. Since both groups were comparable in age, comorbidities, and
      medications, the existing difference is likely to be due to gender-specificity.
      The hemodynamic differences persisted during therapy with metoprolol: resting
      heart rate, blood pressure and rate pressure product were reduced to a greater
      extent in men. During cycloergometry, there was a slight difference in the time
      of onset of ST depression and time of onset of angina, which were slightly higher
      in men, but probably because of the limited number of cases, the difference
      between men and women did not reach significance. On the other hand, with
      metoprolol the duration of exercise and, in parallel, the number of metabolic
      equivalents was significantly greater in males than in females. Thus in spite of
      a presumed greater plasma concentration of metoprolol in women, we found a
      significant difference in anti-ischemic effect in favor of men. We conclude that
      metoprolol might exert a significantly greater therapeutic effect on stress
      induced angina pectoris in men than in women and this difference should be taken
      into account when prescribing this beta-blocker.

PMID- 16636545
TI  - Evaluation of exercise capacity with cardiopulmonary exercise testing and type B
      natriuretic peptide concentrations in adult patients with patent atrial septal
      defect.
AB  - Adults with patent atrial septal defect (ASD) usually find their exercise
      capacity satisfactory, and therefore hesitate to accept proposed surgical
      treatment of the heart disease. The aim of our study was to evaluate both the
      exercise capacity, using the cardio-pulmonary stress test, and brain natriuretic
      peptide (BNP) levels in asymptomatic adults with ASD. Thirty-six patients with
      patent secundum type ASD (aged mean 44.7 +/- 8.2 years) were studied. The control
      group consisted of 25 healthy subjects at the mean age of 45.6 +/- 6.1 years.
      Echocardiography and CPST were performed and BNP levels measured in all subjects.
      Oxygen uptake (VO2 max) was lower in ASD patients than in controls (22.1 +/- 5.6
      vs. 30.0 +/- 6.8 ml/kg/min, p = 0.00001); the VE/VO2 slope was elevated in ASD
      patients compared with healthy subjects (31.3 +/- 6.6 vs. 26.9 +/- 3.3, p =
      0.001), and exceeded 34 in 5 patients. VO2 max showed a negative correlation with
      the pulmonary to systemic flow ratio Qp:Qs (r = -0.46, p = 0.004), and a positive
      correlation was found between the VE/VO2 slope and Qp:Qs (r = 0.32, p = 0.05).
      BNP levels were higher in the ASD group than in the controls (60.6 +/- 49.9 vs.
      32.6 +/- 24.5 pg/ml, p = 0.02). BNP correlated positively with RV diameter and
      Qp:Qs (r = 0.38 and 0.39 respectively, p = 0.03) and negatively with maximum VO2
      (r = -0.5, p = 0.004) and VO2% (r = -0.32, p = 0.07). CONCLUSIONS: Although most
      adult patients with ASD perceive their exercise capacity as satisfactory,
      objective assessment reveals that in fact it is significantly decreased. BNP
      levels are increased comparing to healthy individuals. Decreased exercise
      capacity and increased BNP levels seem to result from right ventricular volume
      overload.

PMID- 16636546
TI  - Progression of advanced interatrial block to atrial flutter: a prospectively
      followed case.
AB  - Interatrial block (IAB; P wave > or = 110 ms), commonly associated with left
      atrial enlargement and its electromechanical dysfunction, is also a significant
      correlate of atrial tachyarrhythmias. While the arrhythmogenic mechanisms of
      atrial fibrillation and atrial flutter may indeed differ, there is actually
      considerably less literature showing evidence of prospective progression of IAB,
      be it partial or advanced, to atrial flutter. We present a unique case of atrial
      flutter occurring within months of diagnosis of advanced IAB in an otherwise
      healthy female to briefly generate our discussion on the possible reasons for
      this scenario.

PMID- 16636547
TI  - Unusual appearance of mitral annular calcification mimicking intracardiac tumor
      prompting early surgery.
AB  - Although mitral annular calcification (MAC) is usually easy to diagnose by
      transthoracic echocardiography, we experienced a rare case with MAC which looked
      like an intracardiac tumor. The patient who had been on chronic hemodialysis for
      20 years was admitted to our hospital because of dyspnea. Transthoracic
      echocardiography showed a mass with severe calcification on the anterior mitral
      annulus and mean mitral gradient of 20 mm Hg. Because of the suspicion of the
      intracardiac calcified tumor that restricted mitral valve motion causing mitral
      obstruction, she underwent resection of the mass and mitral valve replacement.
      Pathological findings showed that the mass had a calcified envelope containing
      liquefied necrotic eosinophilic material with lympocytic infiltrate inside
      consistent with MAC. We should consider a possibility of MAC when we see a severe
      calcified mass attached to the mitral annulus in a patient on long-term
      hemodialysis.

PMID- 16636548
TI  - Weaning in children with congenital heart diseases from nutritional tube is
      easier than in other children.

PMID- 16636549
TI  - Surgery for obesity: panacea or Pandora's box?
AB  - BACKGROUND: Given the increasing prevalence of obesity, healthcare providers
      should be cognizant of various non-operative (diet, exercise, behavior therapy,
      and medications) and operative obesity treatments. This review critically
      evaluates these treatments, especially bariatric surgeries. METHODS: Medline
      analyses using a combination of the following terms: obesity, bariatric surgery,
      and outcomes were performed with particular emphasis on prospective studies and
      randomized trials. RESULTS: Non-operative treatments result in modest sustained
      weight loss (5-8%) at one year. Surgery is recommended for those with BMI >40 or
      >35 with comorbidities. Laparoscopic adjustable gastric banding, a restrictive
      procedure, causes 35-54% excess weight loss (EWL) at 1 year. Malabsorptive
      procedures (biliopancreatic diversions with and without duodenal switch) induce
      72-77% EWL but are only performed at few centers. Roux-en-Y gastric bypass,
      acting through a combination of restriction and malabsorption, results in 69% EWL
      at 1 year and 49% at 14 years. Each procedure is associated with unique anatomic
      and nutritional complications. Overall, operative treatment improves
      comorbidities and may improve all-cause mortality. CONCLUSIONS: Surgery is an
      effective long-term treatment for selected obese patients who have failed other
      treatments. Further research is needed on prospective comparisons of procedures,
      evaluation of long-term outcomes, especially between centers and increasingly
      unrealistic patient expectations.

PMID- 16636550
TI  - A new method for constructing an ileal J pouch without an enterotomy.
AB  - The conventional methods of making an ileal J pouch require an enterotomy to
      introduce a linear stapler. We devised a new surgical technique that removes any
      need for this enterotomy by using both circular and linear staplers. We applied
      this method to two patients who underwent a total colectomy for ulcerative
      colitis and succeeded in making a J pouch without difficulty. This procedure may
      represent an improved method of making a J pouch.

PMID- 16636551
TI  - Diverticulosis of the appendix.

PMID- 16636552
TI  - Oesophageal achalasia with epiphrenic diverticulum with laparoscopic approach: a
      6-year follow-up.

PMID- 16636553
TI  - Seasonal variation of Bell's palsy in Athens, Greece - a hospital-based
      retrospective evaluation over fifteen years.
AB  - Epidemiological data on the incidence of Bell's palsy (BP) are conflicting. The
      aim of this retrospective study was to evaluate the variation of cases of BP
      acutely presented in the emergency room of our department over a 15-year period
      (January 1990 to December 2004). We examined the monthly and seasonal
      distribution of BPs among 36,312 patients who came to our emergency services and
      compared it with the assumed equal distribution of cases over the year (null
      hypothesis) using chi(2) techniques. During the observation period 1,252 of all
      patients (3.45%) presented due to BP. A decline during the summer was observed,
      in contrast to a peak documented during the autumn and winter. January and July
      were the months with the highest and lowest frequency of BP, respectively.
      Statistical analysis revealed a significantly different seasonal (chi(2) =
      10.569; d.f. = 3; p = 0.014) and monthly (chi(2) = 25.445; d.f. = 11; p = 0.008)
      pattern of BP cases. The distribution of cases of BP shows a significant
      variation with a decline during the summer and an increase during the colder
      period of the year. A similar pattern has been described for reactivated herpetic
      ocular infections. Since a similar pathogenetic mechanism is regarded as the main
      cause of BP, the chronobiological aspects and the influence of meteorological
      factors on the reactivation of latent infections deserves further prospective
      evaluation.

PMID- 16636554
TI  - A novel mutation in ATP7B gene associated with severe neurological and
      psychiatric symptoms.

PMID- 16636555
TI  - Higher serum triglyceride level in patients with acute ischemic stroke is
      associated with lower infarct volume on CT brain scans.
AB  - We investigated the relationship between serum triglyceride level and acute
      ischemic stroke severity using infarct volume on CT brain scans as a marker. A
      total of 121 consecutive acute ischemic stroke patients (53 males and 68 females,
      age 47-93 years) with anterior circulation (75%), posterior circulation (9%) or
      lacunar infarcts (16%) were examined. All patients were admitted within 24 h of
      the symptom onset, and CT scans were taken over the subsequent 24-72 h. With
      adjustment for the infarct type, age, sex, timing of CT imaging (24-36, >36-48 or
      >48-72 h since admission), atrial fibrillation, hypertension, fasting cholesterol
      and glucose levels, a higher (> or =1.70 mmol/l) fasting serum triglyceride level
      (within 24 h after admission) was associated with a lower infarct volume (p =
      0.014). In line with a recent report on milder clinical symptoms in acute
      ischemic stroke patients with higher triglycerides, the results suggest an
      independent association between serum triglyceride level and stroke severity.

PMID- 16636556
TI  - Devic's neuromyelitis optica: a case with mitochondrial DNA mutations.

PMID- 16636557
TI  - Progressive facial asymmetry due to trigeminal motor neuropathy.

PMID- 16636558
TI  - Chorea induced by low-dose trazodone.

PMID- 16636559
TI  - An autopsy case of Schilder's variant of multiple sclerosis (Schilder's disease).

PMID- 16636560
TI  - Three in one: case report supporting different origins of essential and
      parkinsonian tremors.

PMID- 16636561
TI  - Another case of voltage-gated potassium channel antibody-related encephalopathy?

PMID- 16636562
TI  - Reply to the paper by Wiendl et al.: diffusion abnormality in Balo's concentric
      sclerosis: clues for the pathogenesis.

PMID- 16636563
TI  - Morphological and functional aspects of the senile larynx.
AB  - OBJECTIVE: To analyze the senile larynx, considering morphological aspects during
      respiration and functional aspects during phonation, comparing it to the young
      adult larynx. PATIENTS AND METHODS: A retrospective study was conducted of 100
      laryngeal images of adults without vocal complaints, 50 laryngeal images of young
      adults aged 20-45 years and 50 laryngeal images of elderly individuals aged 65-85
      years, of both genders. Images were produced by means of a rigid endoscope and
      stroboscopy. The morphological aspects analyzed were: laryngeal symmetry, vocal
      fold bowing, prominence of the vocal process and glottic proportion. The
      functional aspects analyzed were glottic closure, laryngeal vestibule behavior,
      phase (timing of closure) and amplitude symmetry of mucosal wave and tremor of
      laryngeal structures. RESULTS: Significant differences between the young adult
      larynx and the geriatric larynx were found for the following parameters: vocal
      fold bowing, prominence of the vocal process, glottic proportion, phase and
      amplitude symmetry of mucosal wave and tremor of laryngeal structures.
      CONCLUSION: The data suggests that the geriatric larynx differs from the young
      adult larynx in many characteristic aspects.

PMID- 16636564
TI  - Risk factors for voice problems in teachers.
AB  - In order to identify factors that are associated with voice problems and voice
      related absenteeism in teachers, 1,878 questionnaires were analysed. The
      questionnaires inquired about personal data, voice complaints, voice-related
      absenteeism from work and conditions that may lead to voice complaints and
      absenteeism. Different factors play a role in the development and consolidation
      of voice problems. Physical and psycho-emotional factors appear to be the most
      important risk factors. Remarkably, voice load and environment seem to be less
      important as risk factors in the development and consolidation of voice
      complaints. Teachers who experienced voice problems during their training
      reported more voice problems during their career. The results of this study
      stress the importance of a multifactorial approach in the diagnosis and treatment
      of voice problems, whereby physical and psycho-emotional aspects should be
      considered as sensitive to the risk of developing voice problems. Moreover, this
      study shows the crucial importance of adequate voice training during the teacher
      training programme.

PMID- 16636565
TI  - The pitch rise paradigm: a new task for real-time endoscopy of non-stationary
      phonation.
AB  - As standard stroboscopy is restricted to the recording of periodic vocal fold
      vibrations, observations of non-stationary laryngeal mechanisms demand real-time
      recording systems, the most advanced being the high-speed video technique. It
      allows the registration of laryngeal parameters during a variation of the
      fundamental frequency. The aim of this study was to compare amplitude and
      frequency parameters of vocal fold vibration during stationary and non-stationary
      phonation, i.e. a monotonous pitch rise. Twenty-nine young female adults with no
      incidence of voice disorders were examined while performing two different
      phonation tasks: sustained phonation with a constant frequency and a monotonous
      pitch rise. Endoscopic recordings and the acoustic signals were acquired
      simultaneously. Both acoustic and laryngeal parameters were derived for short
      time intervals of 17.8 ms for the constant pitch and pitch rise conditions.
      Instantaneous frequency, sound pressure level, vibratory amplitudes of the vocal
      folds and the type of glottal closure were compared. At the beginning of the
      pitch rise, the acoustic and laryngeal parameters were similar to the parameters
      that occurred within the sustained phonation conditions. In contrast, the
      laryngeal parameters at the middle and at the end of the pitch rise differed
      substantially from those during sustained phonation. For the first time,
      quantitative measures of the growing glottal chink and the vibration amplitude
      decrease during pitch increase could be taken. In general, the image evaluation
      of the pitch rise paradigm can be subdivided into the starting, the raising and
      the final phase. As each phase can be considered as quasi-stationary, existing
      software modules are capable of analysing the process by treating each phase
      separately. Hence, the pitch rise condition may be suitable for clinical
      examination to detect information of voice disturbances that cannot be visualized
      during sustained phonation.

PMID- 16636566
TI  - Epidemiology of voice problems in Dutch teachers.
AB  - In order to assess voice complaints and absence from work due to voice problems
      among teachers of primary and secondary education, as well as among a control
      group, 2,117 questionnaires were analysed. The total group consisted of 1,878
      teachers and 239 controls. Female teachers more frequently reported voice
      complaints and absence from work due to voice problems than their male
      colleagues. No unequivocal relationship between age on the one hand and voice
      complaints and absence from work due to voice problems on the other hand was
      observed. Therefore, the percent of cases was corrected for gender but not for
      age. More than half of the teachers reported voice problems during their career
      and about one fifth had a history of absence from work due to voice problems.
      These numbers are relatively high compared to those of the controls with as well
      as to those without a vocally demanding profession. More than 20% of the teachers
      sought medical help or had been treated for a voice problem. Remarkably, more
      than 12% of the teachers had experienced voice problems during their training and
      this group reported significantly more voice complaints and absence from work due
      to voice problems in their career than the colleagues without voice problems
      during the training. The results of the Voice Handicap Index scores followed
      these trends. These findings point at voice problems during education as a risk
      factor for getting voice problems during the career. The results of this study
      clearly demonstrate that teaching is a high-risk profession for the development
      of voice problems, which is in accordance with other studies and support the
      contention that voice is a worldwide problem in the teaching profession.
      Furthermore, this study indicates the importance of voice care not only during
      training for the profession but also during the career.

PMID- 16636567
TI  - The influence of utterance position on children's production of lexical stress.
AB  - Previous studies reporting acoustical data on children's production of lexical
      stress examined words produced in isolation (i.e., with no carrier phrase) or in
      utterance-final position. In such contexts, the final syllable of the words being
      examined was also the utterance-final syllable. Syllables produced in utterance
      final position are known to be longer in duration and lower in intensity and F(0)
      compared to other syllables within utterances. Therefore, utterance-final effects
      may have obscured previous results on children's production of stress. Twenty
      children at approximately 6 years of age produced novel trochaic and iambic words
      in utterance-final and utterance-non-final position. Comparing productions across
      the two utterance positions suggested that reliance upon the utterance-final
      context was a confounding factor in past studies. Utterance-final position
      facilitated the iambic pattern of duration (short-long) and the trochaic pattern
      of intensity and F(0) (high-low). Utterance position sometimes affected trochees
      differently than iambs, especially in the duration of word-final syllables. The
      results are discussed in terms of past explanations of utterance position effects
      on acoustic characteristics of syllables.

PMID- 16636568
TI  - Measurements of vocal fold elasticity using the linear skin rheometer.
AB  - OBJECTIVE: The linear skin rheometer (LSR), which measures skin visco-elasticity,
      was adapted for measurements of vocal fold properties. A series of studies was
      performed on animal and human excised larynges to determine if the LSR technique
      can be applied to the vocal fold. METHODS: In excised larynges, small patches of
      mucosa were driven sinusoidally at 0.3 Hz over distances of 1-2 mm using a small
      probe. Forces in the order of 1 g equivalent gave optimal measurements. Stiffness
      and viscosity values were derived from stress/strain data. RESULTS: The
      instrument was able to measure the visco-elasticity of the tissue in a repeatable
      manner and it could detect areas where the tissue was artificially stiffened. Two
      dimensional maps of the mechanical properties of the laryngeal mucosa were
      obtained showing local variations in elasticity both parallel and perpendicular
      to the vocal fold edge. Initial studies were undertaken using animal tissue; more
      recently, the LSR has been successfully used to obtain similar data from human
      tissue. CONCLUSION: The LSR was been demonstrated to be capable of measuring the
      elastic properties of the vocal fold in a repeatable and reliable manner. Further
      studies will now be undertaken to obtain data from a larger sample of human
      tissue.

PMID- 16636569
TI  - Estimating the intelligibility of speakers with dysarthria.
AB  - Many speakers with dysarthria have reduced intelligibility, and improving
      intelligibility is often a primary intervention objective. Consequently,
      measurement of intelligibility provides important information that is useful for
      clinical decision-making. The present study compared two different measures of
      intelligibility obtained in audio-only and audio-visual modalities for 4
      different speakers with dysarthria (2 with mild-moderate dysarthria; 2 with
      severe dysarthria) secondary to cerebral palsy. A total of 80 college-aged
      listeners provided word-by-word transcriptions and made percent estimates of
      intelligibility which served as dependent variables. Group results showed that
      transcription measures were higher than percent estimates of intelligibility
      overall. There was also an interaction between speakers and measures of
      intelligibility, indicating that the difference between transcription scores and
      percent estimates varied among individual speakers. Results revealed a
      significant main effect for presentation modality, with the audio-visual modality
      having slightly higher scores than the audio-only modality; however, presentation
      modality did not interact with speakers or with measures of intelligibility.
      Results suggest that standard clinical measurement of intelligibility using
      orthographic transcription may be more consistent than the use of more subjective
      percent estimates.

PMID- 16636570
TI  - Cost-effectiveness analysis of various screening methods for osteoporosis in
      perimenopausal Thai women.
AB  - OBJECTIVE: To perform a health economics analysis of 5 screening programs for
      osteoporosis in perimenopausal Thai women comparing two alternatives; without
      intervention and universal treatment without screening. DESIGN: A decision
      analysis was performed to evaluate five screening strategies: Dual energy X-ray
      absorptiometry (DXA), Quantitative ultrasound sonography (QUS), risk index
      (clinical risk factors), two-step screening with QUS followed by DXA, and
      screening with risk index followed by DXA, comparing outcomes without
      intervention and universal treatment without screening. RESULTS: The costs for
      universal treatment, screening by DXA with treatment, screening by QUS with
      treatment, screening by Risk index with treatment, screening by QUS and DXA with
      treatment, and screening by Risk index and DXA with treatment strategies to
      prevent one fracture were 207.82, 88.42, 147.05, 127.67, 71.33, and 60.30 USD,
      respectively. The cost for no intervention to prevent one fracture is 8.49 USD (1
      USD = 40 Thai baht). CONCLUSION: At present, no intervention is the most cost
      effective strategy. However, screening with risk index and DXA with treatment
      became the most cost effective when the patients reached the postmenopausal
      period and had a high risk index, for which the prevalence of osteoporosis will
      increase. Cost effective screening guidelines still cannot be explicitly
      established until further data addressing the association between bone mass
      measurements in the hip and hip fracture risk, are available.

PMID- 16636571
TI  - Melanoma metastasis to the breast masquerading as fibroadenoma.
AB  - BACKGROUND: Although primary malignant breast lesions are common, tumor
      metastasis to the breast is rare. Melanoma metastasis to the breast occurs even
      more rarely. CASE: In the present case report, we describe an adolescent girl
      with malignant melanoma metastasis to the breast masquerading as fibroadenoma, in
      which it was impossible to perform differential diagnosis based only on the
      physical examination and ultrasonographic evaluation. The definitive diagnosis
      both of the primary and of the metastatic lesion was reached by
      immunohistochemistry, which revealed positivity to Mart-1 antibody. CONCLUSION:
      Melanoma metastasizing to the breast is occasionally indistinguishable from a
      benign lesion at ultrasonographic evaluation. Emphasis should be made on the
      importance of a correct diagnosis prior to therapeutic management.

PMID- 16636572
TI  - Assessment and communication of lifetime disease risk by genetic counselors:
      maintaining the link between research and practice.

PMID- 16636573
TI  - Qatari DNA variation at a crossroad of human migrations.
AB  - Genomic diversity of the Qatari population was investigated by screening 15
      autosomal short tandem repeats (STRs). Significant departures from genetic
      equilibrium were detected at the D13S317, D19S433 and VWA loci, which persisted
      after applying Bonferroni-type corrections. Gene diversity (GD) values ranged
      from 0.6851 (TPOX) to 0.8813 (D2S1338), while observed heterozygosity (Ho)
      oscillated between 0.3388 (D19S433) and 0.8397 (D2S1338). Interestingly, Ho was
      lower than expected (He) for 14 of the loci analyzed. The information provided by
      these microsatellite markers was analyzed by means of genetic distances,
      multidimensional scaling, hierarchical analyses of the molecular variance (AMOVA)
      and admixture estimations to assess the genetic relationships of Qatar with
      European, Asian, African and other Middle Eastern populations. The main findings
      of the study were the genetic uniqueness of the Qatari population, its strong
      similarity to the United Arab Emirates (UAE) group, a slight genetic
      differentiation with respect to other Arab populations (Syria and Egypt) and
      Turkey, and a certain genetic affinity with sub-Saharan African populations.
      These results are discussed in light of two major issues: the high consanguinity
      rates characterizing the Qatari population and its strategic geographic position
      in the Arabian Peninsula close to major migratory routes, an important pivotal
      contact zone for bidirectional dispersals between Eurasia and Africa.

PMID- 16636574
TI  - Normal range of calcitonin in children measured by a chemiluminescent two-site
      immunometric assay.
AB  - Calcitonin (CT) assay is of considerable importance in the routine evaluation of
      thyroid nodules and for screening and follow-up of patients with medullary
      thyroid carcinoma and their relatives. Aim of this study was to assess the
      reference ranges for CT levels in healthy children and to evaluate possible
      differences in CT levels between sex and age. Serum CT levels were measured by a
      commercially available two-site chemiluminescence immunometric assay (sensitivity
      = 0.2 pg/ml). The ILMA recognizes the mature monomeric form of CT. We evaluated a
      cohort of 125 healthy children and compared these results with those from 98
      healthy adult men and women. The ranges for human CT in children were <0.2-11.7
      pg/ml and <0.2-17 pg/ml for female and male, respectively. No gender differences
      were observed in children population, though higher CT levels were observed in
      males. Serum CT levels did not correlate with age. Adult female had statistically
      significant lower CT levels than female children (p <or=0.05). In the adult
      population, males showed levels of CT higher than females. In conclusion, this
      study provide normal range for children population at different age with a
      sensible two-site chemiluminescent immunoassay. Since the normal range of serum
      CT levels is wider in healthy children than in adults, these data suggest
      establishing different normal range values in different age groups.

PMID- 16636575
TI  - Maternal and cord blood ghrelin in the pregnancies of smoking mothers: possible
      markers of nutrient availability for the fetus.
AB  - AIMS: To investigate the role of ghrelin in maternal and fetal metabolism, we
      determined its value in maternal smoking, a specific cause of reduced placenta
      function and fetal growth. METHODS: In 85 normal term pregnancies, 42 in smoking
      and 43 in non-smoking mothers, we measured ghrelin in the maternal blood at the
      onset of labor and in the cord blood of their 85 singletons immediately after
      birth. We determined the relationships between ghrelin and placental GH (PGH),
      pituitary GH (pitGH), and IGF-I. RESULTS: The newborns of smoking mothers weighed
      0.24 kg less (p < 0.05) than those of non-smoking mothers. Cord blood ghrelin was
      71% higher and PGH and cord blood IGF-I were 34% and 32% lower, respectively, in
      the pregnancies of smoking compared with non-smoking mothers (p < 0.05). Cord
      blood ghrelin was unrelated to pitGH and cord blood IGF-I. Maternal ghrelin was
      unchanged in smoking mothers, increased with maternal fasting duration (r = 0.26,
      p < 0.05), showed no correlation with PGH and negative correlation with cord
      blood IGF-I (r = -0.42, p < 0.01). CONCLUSION: The decrease in placental function
      and fetal growth in smoking mothers is associated with an increase in cord blood
      ghrelin, and no change in maternal ghrelin. Maternal ghrelin concentration
      increases with fasting, and is negatively correlated with cord blood IGF-I: it
      may signal a reduction in the level of nutrients available for placental
      transfer. No correlation supports a role for ghrelin in PGH or pitGH secretion.

PMID- 16636576
TI  - Adventitial neuronal somata.
AB  - Confocal analysis of the whole-mount rat mesenteric branch arteries (MBA)
      revealed nucleated structures with axonal processes which immunostained for
      calcitonin gene-related peptide (CGRP). Immunocytochemistry ruled out the
      possibility that these were immune elements (macrophages and mast or dendritic
      cells) in close proximity with nerve fibers. To test our hypothesis that beta
      CGRP is expressed in the rat MBA, we performed RT-PCR using total RNA isolated
      from the mesenteric artery arcade and intron spanning primers designed to amplify
      188 bp of the beta-CGRP and 333 bp of alpha-CGRP cDNA. The PCR yielded an
      amplicon of the predicted size which was cloned into the pCR 3.1 vector. DNA
      sequence analysis of the insert showed 100% homology with the beta-CGRP cDNA,
      indicating that mRNA encoding beta-CGRP is expressed in the vessel. To learn
      whether neuronal cell bodies are located in the adventitia of MBA, we performed a
      limited collagenase digestion of isolated segments and plated the resulting cells
      in Ham's F12 medium with 10% horse serum on polyornithine-coated cover glasses.
      The medium was replaced after 48 h with Ham's F12 nutrient mixture containing N2
      supplement. This resulted in a mixed population of fibroblasts, a small number of
      smooth muscle cells and a subset of cells that sprouted axons and immunostained
      positively for neuronal cell adhesion molecule and CGRP antigens. Fibroblasts and
      smooth muscle cells did not label with these antibodies. These data demonstrate,
      for the first time, that a population of adventitial neuronal somata (termed
      ANNIES), possibly of sensory nerve origin, is located in small mesenteric
      arteries.

PMID- 16636577
TI  - Effect of L-dopa decarboxylase inhibitor benserazide on renal function in
      streptozotocin-diabetic rats.
AB  - BACKGROUND/AIMS: Benserazide (BZD), an inhibitor of the dopamine synthesis,
      abolished the increase in glomerular filtration rate (GFR) following the infusion
      of a mixed amino acid solution. These results reveal endogenous dopamine as a
      mediator in the renal response to amino acids. The aim of the present study was
      to evaluate whether dopamine is also involved in the regulation of glomerular
      hyperfiltration during the early state of diabetes mellitus (DM). METHODS: Male
      Sprague-Dawley rats were injected with a single dose of streptozotocin (60 mg/kg
      i.p.) for induction of experimental DM (n = 7-8/group). Age-matched non-diabetic
      animals, injected with citrate buffer, served as controls (CON, n = 8/group).
      Clearance experiments were performed 2 weeks after induction of DM in thiopental
      anesthetized rats (80 mg/kg i.p.), which were continuously infused either with
      BZD (30 microg/min/kg) or vehicle (VHC). RESULTS: Mean arterial blood pressure
      was around 110 mm Hg and did not significantly differ among the groups. GFR was
      0.95 +/- 0.02 ml/min/100 g b.w. in VHC-treated CON. BZD treatment did not
      significantly change GFR in the CON group (0.92 +/- 0.06 ml/min/100 g b.w.). As
      expected, glomerular hyperfiltration was observed in diabetic rats infused with
      VHC (1.24 +/- 0.08 ml/min/100 g b.w.). Treatment with BZD significantly reduced
      the diabetes-induced increase in GFR to control levels (0.95 +/- 0.05 ml/min/100
      g b.w.). CONCLUSION: Our results show that the inhibition of dopamine synthesis
      prevented the increase in GFR due to diabetic conditions, indicating that
      endogenous dopamine is involved in the regulation of DM-induced changes in renal
      hemodynamics.

PMID- 16636578
TI  - Proteinuria in diabetic patients--is it always diabetic nephropathy?
AB  - BACKGROUND: Diabetic nephropathy (dNP) is a consequence of type 1 and type 2
      diabetes, typically occurring between 5 and 15 years after diabetes has been
      diagnosed. The coincidence of dNP and diabetic retinopathy (dRP) is well known.
      In this study we correlated the histological findings of the kidney biopsy with
      the clinically expected diagnosis of dNP. PATIENTS AND METHODS: Over a 4-year
      period with a total of 326 kidney biopsies, 85 biopsies were performed on
      patients with diabetes. In all of these patients we had information about
      duration of diabetes and ophthalmological status. Additionally, data about
      proteinuria, urine sediment and autoantibodies were available. The nephrologist
      had to give the suspected diagnosis before the biopsy was performed, using the
      clinical data available. RESULTS: In 57 patients (67%) dNP was predicted
      clinically before biopsy. In 28 patients we expected a different kind of kidney
      disease. Only 43 patients had dNP histologically. In 16 out of 19 patients with
      dRP we also found dNP. 26 patients with dNP did not have dRP. So dRP was very
      specific but not sensitive to predict dNP. On the other hand, all patients
      without dRP but acanthocytes in urine sediment had non-diabetic kidney disease
      (NDKD). In the case of patients with neither dRP nor acanthocytes, it was very
      difficult to distinguish between dNP and NDKD. Acanthocytes and antineutrophil
      cytoplasmatic antibodies with positive antibodies for proteinase 3 or
      myeloperoxidase were found only in NDKD, but ANAs were detected in a wide titer
      range in dNP and NDKD. The known duration of the diabetes ranged from 1 to 40
      years. There were no additional parameters to differentiate this group.
      CONCLUSIONS: Diabetic patients with dRP and proteinuria frequently have dNP. In
      patients without typical retinal findings dNP is less likely, thus a kidney
      biopsy is necessary to confirm the diagnosis. Additional knowledge about urine
      sediment and autoantibodies is helpful, but is not sufficient to differentiate
      NDKD from dNP in the majority of patients.

PMID- 16636579
TI  - Smoking as a risk factor for renal injury in essential hypertension.
AB  - BACKGROUND: Smoking is an important player in the pathogenesis of hypertensive
      nephropathy. To shed more light on this issue, we performed a case-control cross
      sectional study and stratification analyses to evaluate the influence of smoking
      on surrogate markers of kidney injury and oxidative stress in patients supposed
      to have hypertensive nephropathy. The dependence of kidney lesions on the
      'extent' of smoking was determined as well. METHODS: 82 patients with essential
      hypertension and micro- or macro-albuminuria were recruited. The control group
      consisted of 41 sex- and age-matched healthy individuals. Urine albumin
      creatinine ratio and plasma von Willebrand factor activity were analysed as
      markers of endothelial injury. N-acetyl-beta-D-glucosaminidase, transforming
      growth factor-beta1 and 15-isoprostane F2t urine excretions were regarded as
      markers of tubular dysfunction, renal fibrosis and oxidative stress,
      respectively. Patients' smoking habits were recorded and categorized on the basis
      of a self-administered questionnaire. RESULTS: In multivariate regression
      analysis, the independent associations between smoking and urine albumin (p <
      0.05; beta = 0.27), von Willebrand factor activity (p < 0.05; beta = 0.29) and
      urine isoprostanes (p < 0.05; beta = 0.28) were found. When the smokers were
      stratified according to the number of cigarettes smoked per day and the time from
      which they started smoking, 'heavy smokers' and 'long-term smokers' presented
      with higher albumin excretion and higher von Willebrand factor activity than
      'light smokers' and 'short-term smokers', respectively. The passive smokers had
      numerically higher albumin excretion and von Willebrand factor activity than
      nonsmokers. CONCLUSION: The study showed that smoking induces oxidative stress.
      Smoking was also found to be a strong predictor for the extent of endothelial
      injury in patients with hypertensive kidney injury. Subjects who smoke heavily
      and for a long time, as well as passive smokers, seem to be particularly exposed
      to endothelial damage.

PMID- 16636580
TI  - Troponin I testing in dialysis patients presenting to the emergency room: does
      troponin I predict the 30-day outcome?
AB  - BACKGROUND: Troponins are often measured in acutely ill chronic dialysis patients
      admitted to the emergency room, irrespective of their clinical presentation. The
      significance of an elevated troponin level in this setting is unclear. METHODS:
      We identified all chronic dialysis patients presenting over 1 year to a tertiary
      care hospital emergency room who also had at least one cardiac troponin I (cTnI)
      level determination. We evaluated presenting complaints, risk factors for cardiac
      disease, cTnI levels, and major cardiac events (MCE; occurrence of cardiovascular
      death, myocardial infarction, de novo heart failure, or coronary
      revascularization) within 30 days by chart review in 149 patients (79 on
      hemodialysis, 70 on peritoneal dialysis). RESULTS: Chest pain was documented in
      only 29% of the patients. Twenty-two patients (15%) experienced an MCE. The
      incidence of an MCE was the same in patients with and without chest pain. A cTnI
      level >0.1 ng/l was a significant predictor of an MCE (odds ratio 15.2, 95%
      confidence interval CI 5.26, 43.6). The likelihood ratios for MCEs were 0.32 (CI
      0.16, 0.63) for a cTnI level <0.1 ng/l, 0.72 (CI 0.09, 5.5) for cTnI
      concentrations 0.1-0.3 ng/l, 7.8 (CI 4.2, 15) for a cTnI level >0.3, and 11.7 (CI
      4.4, 31) for a cTnI concentration >2.0 ng/l. CONCLUSION: In acutely ill chronic
      dialysis patients presenting to a hospital emergency room, an elevated cTnI level
      indicates an increased 30-day cardiac risk, regardless of their clinical
      presentation.

PMID- 16636581
TI  - Can predialysis hypertension prevent intradialytic hypotension in hemodialysis
      patients?
AB  - BACKGROUND/AIM: Intradialytic hypotension is the most common complication
      associated with hemodialysis, and its cause is multifactorial. However, the
      relationship between hypertension and intradialytic hypotension is not clear. We
      investigated the influence of predialysis blood pressure and antihypertensive
      drugs on intradialytic hypotension. METHODS: Risk factors for intradialytic
      hypotension were analyzed in 111 patients undergoing regular hemodialysis
      treatment and had annual echocardiography performed. The correlation between the
      addition of antihypertensive medications and the incidence of intradialytic
      hypotensive episodes was studied in 21 hypertensive patients. RESULTS: Based on
      multivariate logistic regression analysis, diabetes (odds ratio OR 8.18, 95%
      confidence interval CI 1.47-45.5; p = 0.016), interdialytic weight gain (OR 2.45,
      95% CI 1.24-4.82; p = 0.010), ejection fraction (OR 0.88, 95% CI 0.81-0.95; p =
      0.001), and left ventricular volume (OR 0.97, 95% CI 0.94-0.99; p = 0.013) were
      determined as risk factors for intradialytic hypotension. However, there was no
      association between predialysis blood pressure and intradialytic hypotension.
      After additional antihypertensive medications, the predialysis blood pressure
      fell from 175/85 mm Hg to 154/78 mm Hg (p < 0.0001/p < 0.0001). The mean 24-hour
      interdialytic blood pressure fell from 165/87 mm Hg to 147/80 mm Hg (p < 0.0001/p
      = 0.006). However, the frequency of hypotensive episodes was not increased (p =
      0.77). CONCLUSIONS: Diabetes, excessive interdialytic weight gain, low ejection
      fraction, and low left ventricular volume are independent risk factors for
      intradialytic hypotension. However, no correlation was found between predialysis
      blood pressure values or addition of antihypertensive medications and the
      incidence of intradialytic hypotension. Thus, hypertension may be controlled
      without aggravating intradialytic hypotension in hemodialysis patients.

PMID- 16636582
TI  - Effect of hemodialysis on the thickness of vocal folds: a possible explanation
      for postdialysis hoarseness.
AB  - BACKGROUND: Determining the dry weight of chronically hemodialysed patients is a
      common problem. Patients on intermittent hemodialysis often experience transient
      hoarseness at the end of dialysis. The vocal folds may be affected by the
      hydration state. AIM: To test the hypothesis that postdialysis hoarseness may be
      related to changes in the thickness of the vocal folds. METHODS: Twenty-five
      stable chronic hemodialysis patients underwent endoscopic nasopharyngeal
      laryngoscopy before and after dialysis. Pictures of the vocal folds were taken
      and the folds were measured using computer software. Eighteen vocal folds from 16
      patients were technically adequate for analysis. The change in the width/length
      ratio of the vocal folds (W/L) was used as a measurement of the folds' thickness.
      RESULTS: W/L decreased from 0.175 +/- 0.011 before dialysis to 0.152 +/- 0.009
      after dialysis (p < 0.01, mean reduction 10.9 +/- 3.8%). Patients' weight
      decreased by 4.7 +/- 0.3% (p < 0.0001), systolic blood pressure decreased by 15.0
      +/- 3.1% (p < 0.001), diastolic blood pressure decreased by 13.0 +/- 3.6% (p <
      0.01), and mean blood pressure decreased by 14.1 +/- 3.1% (p < 0.001). Sixty
      percent of the patients had postdialysis hoarseness, and in 72% of the patients a
      decrease in the vocal folds' thickness was observed. CONCLUSIONS: Chronic
      hemodialysis patients may experience transient postdialysis hoarseness, and a
      decrease in the vocal folds' thickness. The latter may result from dehydration.

PMID- 16636583
TI  - Clinicopathological characteristics and outcome of adult patients with hematuria
      and/or proteinuria found during routine examination.
AB  - BACKGROUND: Patients with hematuria and/or proteinuria found during routine
      examination are commonly encountered. To define the clinicopathological
      characteristics and outcome of these patients, 142 patients with definite
      pathological diagnosis were studied retrospectively. METHODS: All the 142
      patients were divided into three groups: pure hematuria (HU, n = 13), concomitant
      hematuria and proteinuria (HUPU, n = 79), and proteinuria alone (PU, n = 50).
      RESULTS: At the time of renal biopsy, 26% of the patients had renal insufficiency
      and 48% of the patients had hypertension. Pathologically, IgA nephropathy (n =
      67) was the most common. A total of 51 patients were enrolled into the follow-up
      group. Finally, urinary abnormalities disappeared in 18% of the patients, 22% of
      HU developed proteinuria, 21% of HUPU and 23% of PU appeared to have a distinct
      increase of proteinuria, and 15% of PU developed hematuria. Seven patients with
      normal blood pressure before became hypertensive and 6% of the patients with
      normal renal function initially developed renal insufficiency. The renal outcome
      was associated with proteinuria and tubulointerstitial lesions. CONCLUSION:
      Because renal pathologic change does not always coincide with clinical
      manifestations, patients with hematuria and/or proteinuria found during routine
      examination do not necessarily imply a favorable outcome, so renal biopsy is
      quite important. Besides, early treatment and careful follow-up are helpful in
      these patients.

PMID- 16636584
TI  - Prediction of coronary artery disease by transesophageal echocardiographic
      detection of thoracic aortic plaque in patients with chronic kidney disease.
AB  - BACKGROUND/AIMS: Our aim was to examine the significance of thoracic aortic
      plaque detected by transesophageal echocardiography (TEE) in the prediction of
      coronary artery disease (CAD) in patients with chronic kidney disease (CKD).
      METHODS: We examined 118 patients (mean age 52 +/- 12 years) with CKD and
      followed them for a mean of 3.4 +/- 0.8 years. The study group included 52
      predialysis patients with moderate to severe CKD (plasma creatinine > or = 200
      micromol/l), 32 patients on dialysis treatment, and 34 renal transplant
      recipients. At baseline, TEE was performed to evaluate thoracic aortic
      atherosclerosis. CAD was defined by a history of a documented myocardial
      infarction, a coronary angiogram or a post-mortem autopsy finding showing
      significant occlusive CAD by the end of the follow-up period. RESULTS: CAD was
      documented in 31 (26%) of the 118 study patients. The presence of thoracic aortic
      plaque had a sensitivity of 100% and a specificity of 37% for CAD and the
      positive and negative predictive values were 36 and 100%, respectively. In the
      subset of 36 patients with morphological findings of coronary arteries by
      angiogram or autopsy, the presence of large thoracic aortic plaques (> or = 3 mm
      in diameter) had a 73% sensitivity and 90% specificity for significant coronary
      artery stenosis. The positive and negative predictive values were 95 and 56%,
      respectively. CONCLUSION: TEE may be used for detecting high-risk patients with
      CKD; the absence of thoracic aortic plaque predicted the absence of CAD, and the
      presence of large aortic plaques predicted significant coronary artery stenosis.

PMID- 16636585
TI  - Reliability of magnetic resonance imaging for measuring the volumetric indices in
      autosomal-dominant polycystic kidney disease: correlation with hypertension and
      renal function.
AB  - BACKGROUND: The purpose of this study was to determine if renal volumetric
      indices can be accurately measured using MRI, and if these volumetric indices are
      associated with hypertension and renal function in patients with autosomal
      dominant polycystic kidney disease (ADPKD). METHODS: For testing the accuracy of
      the MRI-based volume measurements that we proposed for clinical trial, we
      designed phantoms to simulate cysts within the kidney. Fifty-six patients with
      ADPKD were included in this study, and their respiratory compensated T2-weighted
      fast spin-echo images were acquired. The total kidney volume (Vt), cyst volume
      (Vc), and noncystic parenchymal volume (Vp) were measured and the percent cyst
      volume (Pc) was calculated. These volumetric indices were compared with the
      disease progression in the ADPKD patients. RESULTS: The MRI measures of the
      phantoms were accurate. The Vt, Vc and Pc were significantly greater in the
      hypertensive group (n = 35) than in the normotensive group (n = 21) (p < 0.01).
      The Vt, Vc and Pc were significantly greater in the renal failure group (n = 23)
      than in the normal renal function group (n = 33) (p < 0.01). The Vt, Vc, and Pc
      were inversely correlated with the creatinine clearance. CONCLUSION: MRI is a
      reliable method to measure renal volumetric indices. The MRI-based volume
      measurements can be employed as useful markers for the progression of disease in
      ADPKD patients.

PMID- 16636586
TI  - Comparison of methods for counting cells in the mouse glomerulus.
AB  - BACKGROUND: Researchers have long been interested in counting the number of cells
      within the glomerulus. Investigators using different techniques have yielded
      conflicting results. The most direct method is to count the cells in serial
      sections from the entire glomerulus. This Exhaustive Count method is not usually
      practical. The disector/fractionator method counts the number of cells in a
      fraction of sections. The total is estimated from the product of the cell count
      and the reciprocal of the fraction. The Weibel-Gomez method determines the
      density of cells per glomerulus, then multiplies this density by glomerular
      volume to obtain cell number. In this study, we compared the
      disector/fractionator and Weibel-Gomez methods to identify a practical
      alternative for the time-consuming Exhaustive Count method. METHODS: Glomeruli
      from a normal mouse kidney were completely sectioned and images obtained.
      Appropriate images were used to count glomerular cell number using each method.
      RESULTS: The Exhaustive Count method yielded 213 +/- 22 (mean +/- SD)
      cells/glomerulus vs. the disector/fractionator average of 211 +/- 29
      cells/glomerulus (p = 0.82). The Weibel-Gomez method average of 235 +/- 26
      cells/glomerulus was statistically different from the Exhaustive Count method (p
      = 0.003). CONCLUSION: The Weibel-Gomez produced a 10% overestimation, whereas the
      disector/fractionator method was unbiased and thus a good substitute for the
      Exhaustive Count method.

PMID- 16636587
TI  - Connective tissue growth factor is responsible for transforming growth factor
      beta-induced peritoneal mesothelial cell apoptosis.
AB  - BACKGROUND: Previous studies found that transforming growth factor-beta (TGF
      beta) induces mesothelial production of connective tissue growth factor (CTGF),
      which may be downstream mediators of TGF-beta. Since high dose TGF-beta induces
      apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF
      blockade in the system of TGF-beta-induced PMC apoptosis. METHOD: We examined the
      effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC
      apoptosis was studied by flow cytometry. The effect of CTGF was blocked by
      antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was
      studied by real-time polymerase chain reaction. RESULT: In cultured unstimulated
      rat PMC, there is a low but definite incidence of spontaneous apoptosis.
      Stimulation with TGF-beta 50 pg/ml induces an upregulation of apoptotic gene BAX
      expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4
      fold increase in PMC apoptosis. The effect of TGF-beta-induced PMC apoptosis was
      partly prevented by antibody against CTGF, and completely abolished by CTGF
      specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF
      silencing by siRNA prevented the down-regulation of BCL-2L expression induced by
      TGF-beta, had no effect on the BAX expression. CONCLUSION: Our results indicate
      that CTGF is an important downstream mediator of TGF-beta-induced PMC apoptosis.

PMID- 16636588
TI  - Proinflammatory cytokine-induced NF-kappaB activation in human mesangial cells is
      mediated through intracellular calcium but not ROS: effects of silymarin.
AB  - BACKGROUND: It is not fully understood whether intracellular calcium and/or
      reactive oxygen species (ROS) are involved in nuclear factor-kappaB (NF-kappaB)
      activation by proinflammatory cytokines. Silymarin exhibits anti-inflammatory and
      antioxidant effects but the effect of silymarin in human mesangial cells is
      largely unknown. METHOD: NF-kappaB binding activity was measured by
      electrophoretic mobility shift assay. Intracellular calcium was monitored by
      confocal microscopy using Fluo-3 and intracellular ROS production was determined
      by flow cytometry. Monocyte chemoattractant protein-1 (MCP-1) expression was
      measured by Northern blot analysis and ELISA. RESULTS: NF-kappaB was activated
      within 30 min by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL
      1beta). Intracellular ROS was not produced until 30 min and also antioxidants
      such as N-acetylcysteine and tiron had no effect on the TNF-alpha- or IL-1beta
      induced NF-kappaB activation. Intracellular calcium was increased by TNF-alpha
      and IL-1beta. Furthermore, a calcium chelator, BAPTA-AM, attenuated the NF-kappaB
      activation. Silymarin dose-dependently inhibited the TNF-alpha- or IL-1beta
      induced NF-kappaB activation and MCP-1 expression. Silymarin also inhibited TNF
      alpha-induced intracellular calcium. CONCLUSIONS: Induction of NF-kappaB within
      30 min by TNF-alpha- and IL-1beta was mediated through intracellular calcium but
      not ROS. Silymarin inhibited TNF-alpha-induced calcium-dependent NF-kappaB
      activation irrespective of its antioxidant effect.

PMID- 16636593
TI  - Two novel PHEX mutations in Taiwanese patients with X-linked hypophosphatemic
      rickets.
AB  - BACKGROUND: X-linked hypophosphatemic rickets (XLH) is an X-linked dominant
      disease characterized by renal phosphate wasting, hypophosphatemia, aberrant
      vitamin D metabolism, and defective bone mineralization. The disease is caused by
      mutations in the PHEX gene (phosphate-regulating gene with homologies to
      endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX
      mutations have been identified in these patients. METHODS: PCR and direct
      sequencing was performed for all exons and intron-exon boundaries of the PHEX
      gene in two XLH families. RESULTS: Two novel mutations, including a missense
      mutation (L206W) in exon 5 and a frameshift mutation (nucleotide
      1826_1830delAAAAG, stop after codon 610) in exon 18 were discovered and the
      laboratory and radiographic findings for these patients analyzed. CONCLUSIONS: We
      found that PHEX gene mutations were responsible for XLH in these Taiwanese
      patients. Additional studies are needed to enhance understanding of the role of
      PHEX in XLH pathogenesis.

PMID- 16636594
TI  - Study of erythrocyte ATPases in infants evaluated during the recovery phase of
      severe dehydration caused by diarrhea.
AB  - BACKGROUND/AIMS: Patients severely dehydrated from diarrhea are at risk of
      developing hyperkalemia consequent to fluid therapy treatment. In parallel with
      the regulation of external potassium balance by the kidney and gastrointestinal
      tract, plasma potassium is rapidly regulated by redistribution of potassium
      between the extracellular and intracellular compartments. Erythrocytes contain
      ATPases that play a role in this potassium movement. In this study, erythrocyte
      ATPase effectiveness was evaluated in infants dehydrated from diarrhea and
      compared to that of healthy infants. METHODS: Blood samples were collected from
      dehydrated and healthy infants. The activity of Na+,K+-ATPase and of an ouabain
      insensitive K+-ATPase were assessed. Serum electrolytes and blood pH were also
      determined. RESULTS: No hyperkalemia was found, even in dehydrated infants
      presenting with severe hyperchloremic metabolic acidosis. In the erythrocytes of
      dehydrated infants, Na+,K+-ATPase activity was increased correlating positively
      with the amount of sodium administered. High K+-ATPase activity in the
      erythrocytes correlated with low plasma potassium. The K+-ATPase activity
      correlated positively with the amount of potassium administered to dehydrated
      infants. CONCLUSION: These findings suggest that the erythrocytes Na+,K+-ATPase
      and K+-ATPase both protect against plasma potassium abnormalities in dehydrated
      infants. In such infants, the risk of hyperkalemia is probably low.

PMID- 16636595
TI  - Decreased expression of aquaporin water channels in denervated rat kidney.
AB  - AIMS: A neural mechanism regulating aquaporin (AQP) water channels in the kidney
      was investigated. METHODS: Male Sprague-Dawley rats were used. Renal denervation
      was induced by painting the renal vessels with 10% phenol. The expression of AQP1
      4 proteins was determined in the denervated and contralateral kidneys. The
      expression was also examined in rats which were renally denervated and subjected
      to water restriction or deoxycorticosterone acetate (DOCA)-salt treatment.
      RESULTS: Following the unilateral denervation, tissue contents of norepinephrine
      were significantly decreased in the denervated kidney, while increased in the
      contralateral kidney. Accordingly, the expression of AQP1-4 proteins was
      decreased by 15-40% in the denervated kidney, and increased by 30-50% in the
      contralateral kidney. Immunohistochemistry of AQP2 confirmed its decreases in the
      denervated kidney and increases in the contralateral kidney. In bilaterally
      denervated rats, the urine flow increased along with decreased osmolarity. The
      water restriction increased the expression of AQP channels, however, the
      magnitude of which was lower in the denervated than in the contralateral kidney.
      Renal denervation decreased the degree of DOCA-salt hypertension, along with
      lower expression of AQP channels. CONCLUSION: It is suggested that the
      sympathetic nerve should play a specific excitatory role in the regulation of AQP
      channels in the kidney.

PMID- 16636596
TI  - To understand what happens to the foods that you and I eat. An interview with Dr.
      Vay Liang Go. Interview by Martin E. Fernandez-Zapico.
AB  - Vay Liang Go is an internationally renowned pancreatic scientist and clinical
      investigator. Doctor Go's work was fundamental for the understanding of the neuro
      hormonal control of gastrointestinal and pancreatic function and metabolism.
      Additionally, he contributed enormously to the pancreatic community by being one
      of the founders of the American Pancreatic Association and also co-founder of the
      journal Pancreas. He trained a large number of fellows and junior faculties, many
      of whom now are national and international opinion leaders in gastroenterology
      and pancreatology. In this interview, Doctor Go gives us his views and shares his
      professional experiences in pancreatic research.

PMID- 16636598
TI  - Significance of serum receptor-binding cancer antigen (RCAS1) in pancreatic
      cancer and benign pancreatobiliary diseases.
AB  - BACKGROUND/AIMS: RCAS1 is a novel tumor marker, and there are no sufficient data
      about the utility of this antigen as a serum tumor marker and about its tumor
      specificity. We aimed at measuring the serum levels of RCAS1 in patients with
      pancreatic cancer and at determining its diagnostic efficacy. METHODS: Sera
      collected from patients with pancreas adenocarcinomas (39 cases) and benign
      biliary and pancreatic diseases (19 cases) and from healthy volunteers (13 cases)
      were analyzed for RCAS1 and the results compared with CA19-9. The relation
      between serum RCAS1 and tumor stage was also evaluated. RESULTS: The serum RCAS1
      levels exceeded the normal limit in 92.3, 26.3, and 23.0% of the patients with
      pancreatic cancer and benign biliary and pancreatic diseases and healthy
      volunteers, respectively. RCAS1 had a specificity similar to that of CA19-9 in
      pancreatic cancer, whereas RCAS1 had a higher sensitivity (p < 0.05). Both tumor
      markers had similar predictive values of positive and negative tests for
      pancreatic cancer. The RCAS1 level was less influenced than the CA19-9 level by
      biliary stenoses. The median serum levels of RCAS1 increased, as the tumor stage
      increased. CONCLUSIONS: RCAS1 is a valuable serum marker for the diagnosis of
      pancreatic cancer. The RCAS1 and CA19-9 levels increase the diagnostic efficiency
      of each other in pancreatic cancer.

PMID- 16636599
TI  - Phagocytosis and production of H2O2 by human peripheral blood mononuclear cells
      from patients with obstructive jaundice.
AB  - BACKGROUND: The immune function is altered in jaundiced patients; here, the
      ability of their peripheral blood mononuclear cells to perform phagocytosis and
      to release H2O2 was analyzed. METHODS: Cells from 53 patients before surgery for
      relief of cholestasis, from 38 patients 1 week and from 15 patients 2 weeks after
      surgery were separated and cultured for 1 h in the presence of phorbol myristate
      acetate. H2O2 release was evaluated colorimetrically and phagocytosis by the
      ingestion of Escherichia coli in vitro. RESULTS: Before surgery for relief of
      cholestasis, the cells of the patients were unable to release H2O2, but, after
      surgery, an increasing percentage of patients had cells that were able to produce
      H2O2 (13% after 1 week; 33% after 2 weeks). This recovery did not correlate with
      bilirubinemia. When cultured for 1 week in the presence of normal or jaundiced
      plasma, regardless of collection time, cells of 12/12 patients released H2O2, but
      in lower levels if in the presence of jaundiced plasma. In contrast, H2O2 release
      by normal donor cells was enhanced in the presence of jaundiced plasma.
      Phagocytosis by cells of the patients was lower, but when present was associated
      with a significantly higher bactericidal activity. CONCLUSION: These significant,
      but reversible alterations of monocyte function in jaundiced patients might
      contribute to their enhanced susceptibility to surgical complications.

PMID- 16636600
TI  - Obesity increases the severity of acute pancreatitis: performance of APACHE-O
      score and correlation with the inflammatory response.
AB  - BACKGROUND: Obese patients appear to be at risk for complications of acute
      pancreatitis (AP). APACHE-O score has been suggested to improve APACHE-II
      accuracy in predicting severe outcome in AP. AIMS: To determine if APACHE-O adds
      any predictive value to APACHE-II score and to test the hypothesis that obese
      patients are at increased risk of severe AP (SAP) because of a more intense
      inflammatory response to pancreatic injury. METHODS: 102 AP patients were
      prospectively studied. Using a body mass index (BMI) >30, 28% of the subjects
      were obese. Nineteen patients developed organ dysfunction and were classified as
      SAP. Receiver-operating curves for prediction of SAP were calculated using
      admission APACHE-II and APACHE-O scores. Binary logistic regression was performed
      to assess if obesity is a risk for SAP and to determine the clinical factors
      associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as
      Ranson's scores were compared between obese and non-obese patients. RESULTS:
      Admission APACHE-O (area under the curve AUC 0.895) and APACHE-II (AUC 0.893)
      showed similar accuracy in predicting severe outcome. BMI was identified as a
      significant risk for SAP (OR 2.8, p = 0.048) and mortality (OR 11.2, p = 0.022).
      CRP levels were significantly higher in obese AP patients (p = 0.0001) as well as
      Ranson's score (p = 0.021). IL-6 and MCP-1 levels were higher in obese patients
      but did not reach statistical significance. CONCLUSIONS: Obesity is an
      independent risk for SAP. Admission APACHE-O score is not more accurate than
      APACHE-II. Our study results suggest that obesity increases the severity of AP by
      amplifying the immune response to injury.

PMID- 16636601
TI  - Investigation of the relaxant effects of pinacidil and cromakalim on the sheep
      sphincter of Oddi.
AB  - BACKGROUND/AIMS: ATP-sensitive K+ (KATP) channels play an important role in the
      regulation of smooth muscle membrane potential. This study was designed to
      investigate the effects of pinacidil and cromakalim, KATP-sensitive channel
      activators, on sheep sphincters of Oddi (SO). METHODS: SO rings were mounted in a
      tissue bath and tested for changes in isometric tension in response to pinacidil
      (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) in the presence or absence of
      glibenclamide (10(-6)M), a blocker of KATP channels. Furthermore, concentration
      dependent contraction responses of carbachol were obtained. RESULTS: Carbachol
      (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO
      rings. Pinacidil (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) induced
      concentration-dependent relaxation in isolated SO rings precontracted with
      carbachol (10(-6)M). At their maximum effects, both pinacidil and cromakalim
      produced nearly full relaxation. In the presence of glibenclamide, concentration
      relaxation curves for pinacidil and cromakalim underwent rightward parallel
      shifts. There were no significant differences between pEC50 and E(max) values of
      pinacidil and cromakalim in the absence of glibenclamide (10(-6)M) (p > 0.05),
      but pEC(50) values of pinacidil and cromakalim in the presence of glibenclamide
      (10(-6)M) were significantly reduced (p < 0.05). CONCLUSION: These results
      suggest that the relaxation caused in sheep SO by pinacidil and cromakalim is
      mediated through the same glibenclamide-sensitive KATP channel. Pinacidil and
      cromakalim have an equipotent relaxing effect in isolated sheep SO and they can
      be beneficial as alternative drugs for obtaining selective relaxation during SO
      manometry after controlled clinical studies.

PMID- 16636602
TI  - Solid pseudopapillary tumor of the pancreas: report of 8 cases in a single
      institution and review of the Chinese literature.
AB  - BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare disease
      with a low-grade malignant potential. In recent years, the incidence has been
      increasing. No consensus has been reached regarding diagnostic or therapeutic
      strategies. METHODS: Eight cases of SPTP, admitted from 1996 to March 2005, were
      analyzed retrospectively, and all the literature concerning SPTP published in
      Chinese medical journals from January 1994 to March 2005 were analyzed. RESULTS:
      A total of 186 cases have been reported since 1995, among which 162 were females
      (87.1%), with a male to female ratio of 1:6.8. A histogram of the ages at onset
      illustrated an approximately smooth skewed distribution with a single peak, which
      was located between 10 and 19 years. The number of diseases located at the
      pancreatic head is similar to that located at the body and the tail. Malignancy
      was pathologically diagnosed in 22 cases (11.6%). Major clinical presentations
      included abdominal pain of varying degree (43.5%) and palpable abdominal masses
      (37.1%). Treatment strategies include different types of resection, ranging from
      tumor enucleation to multiple organ resection, and the prognosis is generally
      good. CONCLUSIONS: SPTP occurs predominantly in adolescent and young females, and
      a satisfactory effect could be achieved with active and appropriate surgeries.

PMID- 16636603
TI  - The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic
      pancreatitis.
AB  - BACKGROUND AND AIMS: Chronic pancreatitis (CP) is an inflammatory process
      initiated by recurrent acute pancreatitis and characterized by progressive
      parenchyma destruction and fibrosis. Genetic factors influence susceptibility and
      modify progression. The monocyte chemotactic protein-1 (MCP-1) -2518 G allele,
      which modifies the severity of acute pancreatitis, was investigated as a
      susceptibility factor for CP. METHODS: A genetic association study was performed
      on 177 CP patients and 116 healthy controls from the NAPS2 Study. The MCP-1 A/G
      genotype was determined by RFLP and confirmed by DNA sequencing. RESULTS:
      Compared to the control group the MCP-1 -2518 genotypes were similar: A/A (57%
      vs. 50%), A/G (34.5% vs. 40%) and G/G (8.5% vs. 10%). These allele frequencies
      were not statistically different (p = 0.267). CONCLUSIONS: Although the pro
      inflammatory chemokine MCP-1 -2518 G allele is a severity factor for AP, it does
      not significantly alter susceptibility to CP.

PMID- 16636604
TI  - Biocompatibility of a new bioabsorbable radiopaque stent material (BaSO4
      containing poly-L,D-lactide) in the rat pancreas.
AB  - BACKGROUND/AIM: During recent years, we have been developing bioabsorbable
      biliary stents with promising experimental results. In developing pancreatic
      stents before long-term experiments, the acute toxicity to the pancreas of a
      bioabsorbable, radiopaque polylactide (PLA 96-barium sulfate, BaSO4) stent
      material was investigated. METHODS: The pancreas of 65 Sprague-Dawley rats was
      exposed either to radiopaque stent material [PLA 96 with 25% (w/w) of BaSO4],
      radiolucent stent material (PLA 96), or inert steel by inserting a 5-mm-long
      (diameter 0.3 mm) fiber/stick of material into the pancreas after laparotomy
      under general anesthesia. Pancreatic tissue specimens and blood samples were
      taken after 1, 3, 7, and 21 days for histological examination and amylase
      activity measurements. Samples were also taken from 5 baseline (control) rats
      without exposing to any materials. RESULTS: The baseline serum amylase activity
      was normal, and no histological changes in the pancreas were observed. A
      significant increase (mean +/- SE) in the serum amylase activity was observed
      only on day 1 in the animals having radiopaque stent material (PLA 96-BaSO4;
      5,845 +/- 1,135 U/l), steel (4,946 +/- 667 U/l), or radiolucent stent material
      (PLA 96; 7,684 +/- 667 U/l) inserted. There was slightly more acinar cell
      necrosis on day 7 in the steel group than in the radiopaque stent (PLA 96
      BaSO(4)) group (p = 0.028). CONCLUSIONS: Radiopaque stent material (PLA 96-BaSO4)
      was not more toxic than the reference steel material in the rat pancreas during
      the 21-day observation period and is thus applicable for further in vivo
      experiments when developing pancreatic bioabsorbable stents.

PMID- 16636605
TI  - Cerebellar metastasis from pancreatic adenocarcinoma. A case report.
AB  - The first discovery of a cerebellar metastasis of pancreatic carcinoma in a
      living patient is described. Two years earlier the patient had undergone a
      pancreaticoduodenectomy for an adenocarcinoma of the head of the pancreas with a
      lymph node metastasis. After complete surgical removal of the tumor, he underwent
      adjuvant chemoradiation. Two years later the patient presented with intractable
      vomiting, which was attributed to peritoneal carcinomatosis. Clinical evaluation
      revealed an intracranial tumor without signs of pancreatic recurrence. The tumor
      was surgically removed. One year later the patient developed multiple brain
      metastases and he is currently undergoing gemcitabine-based chemotherapy.

PMID- 16636606
TI  - Severe acute pancreatitis and pregnancy.
AB  - For most patients with pregnancy-associated pancreatitis there is little maternal
      survival threat and only occasionally are there foetal deaths. We describe 4
      young women with pregnancy-associated severe acute pancreatitis who each had
      gallstones. Their ages were 17, 18, 20 and 24 years. Each was a tertiary referral
      to our unit in Glasgow and each pursued a life-threatening course with hospital
      stays ranging from 37 to 90 days. One patient required pancreatic necrosectomy
      for infected necrosis, another had percutaneous management of a pancreatic
      abscess and 2 had cystogastrostomy as treatment for pancreatic pseudocyst. All
      underwent early endoscopic sphincterotomy and later cholecystectomy. It is
      important to be aware that pregnancy-associated acute pancreatitis may be severe,
      posing a survival threat even in the youngest patients. Gallstones, as we
      reported almost 20 years ago, are the most common aetiological factor in such
      patients.

PMID- 16636607
TI  - MMP-9 in serum correlates with the development of pulmonary complications in
      experimental acute pancreatitis.
AB  - INTRODUCTION: The prediction of the course of acute pancreatitis and its arising
      complications is of clinical importance. The aim of this study was to judge the
      time course and relevance of matrix metalloproteinase-9 (MMP-9), a PMN-derived
      protease, for the development of pulmonary complications in two models of acute
      pancreatitis. METHODS: MMP-9 was evaluated in a standardized experimental model
      of acute pancreatitis. Mild edematous (n = 12) and severe necrotizing
      pancreatitis (n = 48) were induced by intravenous cerulein or intravenous
      cerulein and intraductal application of glycodeoxycholic acid and compared to
      control animals. 1, 6, 9, 12, 24 and 72 h after induction, rats were sacrificed
      and damage to the lung and the pancreas was quantified by histology and
      extravasation of Evans blue. At 1, 6, 9, 12, 24 and 72 h, we determined MMP-9 in
      serum by ELISA. RESULTS: In our model, MMP-9 in serum was increased in the group
      with severe acute pancreatitis in comparison to mild edematous pancreatitis and
      controls at each evaluated time point (p < 0.05). The maximum release of MMP-9
      preceded the development of pulmonary complications, verified by histology and
      extravasation of Evans blue. MMP-9 showed a negative predictive value of 96.2%
      and a positive predictive value of 100% for the development of pulmonary
      complications. CONCLUSION: MMP-9 in serum allows a valid grouping to severe and
      mild courses of experimental acute pancreatitis with a good predictive value for
      the development of pulmonary complications. MMP-9 should be evaluated as a valid
      single marker for the prediction of progression and the development of pulmonary
      complications in acute pancreatitis in clinical studies.

PMID- 16636610
TI  - Effects of schisandrin B enantiomers on cellular glutathione and menadione
      toxicity in AML12 hepatocytes.
AB  - Effects of schisandrin B enantiomer ((+)Sch B and (-)Sch B) treatment on the
      reduced cellular glutathione (GSH) level and susceptibility to menadione-induced
      toxicity were investigated and compared in AML12 hepatocytes. (+)Sch B or (-)Sch
      B treatment at 6.25 micromol/l produced a time-dependent change in cellular GSH
      level, with the maximal stimulation occurring 16 h after dosing. (+)Sch B/(-)Sch
      B pretreatment for 16 h dose-dependently protected against menadione toxicity,
      with the maximum degree of protection observable at 6.25 micromol/l and the
      extent of protection afforded by (-)Sch B being larger than that of (+)Sch B. The
      cytoprotection was associated with a parallel enhancement in cellular GSH level
      in both non-menadione (control) and menadione-intoxicated cells. While the GSH
      depletion produced by buthionine sulfoximine/phorone treatment largely abrogated
      the cytoprotective action of (+)Sch B/(-)Sch B, it almost completely abolished
      the GSH-enhancing effect of (+)Sch B and (-)Sch B in both control and menadione
      treated cells. Both (+)Sch B and (-)Sch B treatments increased the GSH reductase
      activity in control and menadione-treated cells, with the stimulatory action of (
      )Sch B being more potent than that of (+)Sch B in the control condition. (+)Sch B
      and (-)Sch B also enhanced the gamma-glutamate cysteine ligase activity in
      menadione-intoxicated cells. The results indicate that (-)Sch B is more effective
      than (+)Sch B in enhancing cellular GSH and protecting against oxidant injury in
      hepatocytes.

PMID- 16636612
TI  - Pseudoclosure of anterior fontanelle by wormian bone in isolated sagittal
      craniosynostosis.
AB  - AIMS AND OBJECTIVES: Although syndromic craniosynostosis is one of the causes for
      early closure of the anterior fontanelle, there is no literature on the incidence
      and causes of fontanelle closure in isolated single-suture craniosynostosis. The
      objective of this study was to review the incidence of fontanelle closure by a
      wormian bone in isolated, nonsyndromic sagittal craniosynostosis. MATERIALS AND
      METHODS: Intraoperative records of 100 consecutive children under 1 year of age,
      operated for isolated sagittal synostosis over a 14-year period (1987- 2000),
      were reviewed to identify the presence of a wormian bone closing the anterior
      fontanelle. RESULTS: The median age at surgery was 4.2 months with a range of 1.9
      11.7 months. Intraoperatively, a wormian bone was seen replacing the anterior
      fontanelle in 4 cases giving an incidence of 4%. CONCLUSIONS: A wormian bone can
      occupy the anterior fontanelle in children with isolated sagittal
      craniosynostosis giving the appearance of a 'closed fontanelle'.

PMID- 16636611
TI  - Influence of baicalin on the expression of receptor activator of nuclear factor
      kappaB ligand in cultured human periodontal ligament cells.
AB  - BACKGROUND: Baicalin is a flavonoid purified from the medicinal plant Scutellaria
      baicalensis Georgi. It has been reported that baicalin exhibits antibacterial,
      anti-inflammatory and analgesic effects and can inhibit nuclear factor-kappaB
      activation. Periodontal disease is a chronic infective disease of the
      periodontium caused by bacteria present in dental plaque inducing alveolar bone
      resorption until teeth are lost. Human periodontal ligament (HPDL) is the
      connective tissue between alveolar bone and tooth. Receptor activator of nuclear
      factor-kappaB ligand (RANKL), a member of the tumor necrosis factor (TNF) ligand
      family, plays an important role in osteoclastogenesis from osteoclast precursors
      to mature osteoclasts. In this study we investigate the effects of baicalin on
      RANKL protein production and messenger RNA (mRNA) expression induced by IL-1beta
      in cultured HPDL cells. METHODS: To induce RANKL expression, IL-1beta was added
      to serum-free medium HPDL cells and incubated. Various concentrations of baicalin
      (0, 0.001, 0.01 and 0.1 microg/ml) were added to the medium and the cells were
      treated for 0, 12, 24, 48 and 72 h, respectively. RANKL in the cells was detected
      using immunocytochemistry. The mRNA of RANKL, osteoprotegerin (OPG) and
      cyclooxygenase-2 (COX-2) were measured by semiquantitative reverse transcription
      polymerase chain reaction. RESULTS: The expression of RANKL at mRNA and protein
      levels in HPDL cells was stimulated by IL-1beta. Baicalin suppressed IL-1beta
      induced RANKL and COX-2 production at a concentration of 0.01 microg/ml. The most
      prominent effect was observed with 48 h of baicalin treatment. The inhibition of
      baicalin on the rhIL-1beta-stimulated OPG expression was first apparent at 24 h
      after the start of treatment, however it did not reach significant differences.
      CONCLUSIONS: The data suggest that baicalin may inhibit RANKL mRNA expression via
      the suppression of COX-2 expression induced by IL-1beta. In addition to its
      antibacterial and anti-inflammatory properties, baicalin was shown to be
      effective in periodontitis and alveolar bone resorption.

PMID- 16636613
TI  - Penetrating craniofacial injuries in children with wooden and metal chopsticks.
AB  - Penetrating craniofacial injuries with chopsticks in children are peculiar
      accidents in the Oriental culture. All 10 cases previously reported were caused
      by wooden chopsticks that required surgical operations. However, there are no
      reported injuries with metal chopsticks in the past literature which should have
      been as common as that of wooden chopstick injuries in Asia. We evaluated the
      difference of injury patterns and clinical observations between wooden and metal
      chopstick injuries. We reviewed 6 treated children with penetrating craniofacial
      injuries from chopsticks: one wooden and five metal chopsticks. One child who had
      penetration through the nasal cavity presented with temporary rhinorrhea, another
      with mild hemiparesis, and one child with temporary upward gaze limitation of the
      left eye. Radiological examination revealed 1 patient with epidural hemorrhage, 1
      patient with minimal subdural hemorrhage, and 4 with intracerebral hemorrhage
      that were fortunately too small to receive surgery. We performed surgical
      procedure only for a child who had a wooden chopstick that had impacted into the
      temporal cortex. We followed up all 6 children for more than 1 year, and found
      that all had fully recovered to near-normal neurological status. We observed that
      penetrating craniofacial injuries with metal chopsticks rarely require surgical
      intervention and usually results in good outcome because the resultant wound is
      usually small without broken fragments compared to injuries with wooden
      chopsticks.

PMID- 16636614
TI  - Third ventricular colloid cysts in children.
AB  - INTRODUCTION: Colloid cysts of the 3rd ventricle are relatively rare intracranial
      tumours, more so in children. They are benign tumours with excellent prognosis if
      diagnosed and treated early. METHODS: A retrospective analysis of 18 cases of
      colloid cysts in children below 18 years, operated in our institution between
      September 1998 and November 2003 (5 years) was made. Clinical presentation,
      radiological findings, surgical approaches and outcome were analysed. RESULTS:
      Age ranged from 7 to 18 years. The male-to-female ratio was 12:6. Headache and
      vomiting were the most common symptoms. Papilloedema was the most common clinical
      sign. Pre-operative CT showed a hyperdense non-enhancing lesion in the majority.
      Twelve patients underwent a transcallosal, 2 a transcortical and 4 an endoscopic
      approach. Ventriculoperitoneal shunts were done in 5 patients. Postoperatively 2
      patients developed epidural haemorrhage which required evacuation. One patient
      was re-explored for symptomatic residue. A mean follow-up of 10.2 months was
      available in 9 patients; the majority were asymptomatic. CONCLUSION: Colloid
      cysts though rare are increasingly detected in children. Their early recognition
      and treatment give excellent results.

PMID- 16636615
TI  - CSF shunt failure with stable normal ventricular size.
AB  - OBJECTIVE: The purpose of this study was to review the clinical features of a
      group of patients in whom ventricular enlargement was not a manifestation of
      prolonged CSF shunt obstruction. RESULTS: Twelve patients who had prolonged
      symptoms consistent with CSF shunt failure and stable normal ventricular size
      were demonstrated at the time of surgery to have obstruction of their CSF shunts.
      CONCLUSION: Ventricular enlargement is a common but not sine qua non indicator of
      CSF shunt failure, even after weeks or months of elevated intracranial pressure,
      and therefore cannot be relied upon for the diagnosis of CSF shunt failure.
      Although an increase in ventricular size is usually seen relatively early in the
      course of shunt malfunction, stable normal ventricular size in patients with
      symptoms and signs that are consistent with shunt failure can delay the diagnosis
      with potentially serious adverse consequences.

PMID- 16636616
TI  - Laparoscopy-guided insertion of peritoneal catheters in ventriculoperitoneal
      shunt procedures: analysis of 39 children.
AB  - Ventriculoperitoneal shunting is the mainstay in the treatment of hydrocephalus
      in childhood. Repeated shunt revision and previous laparotomy may complicate the
      implantation of the distal catheter. We describe our experience with laparoscopic
      insertion of peritoneal catheters in 21 male and 18 female children with an age
      range from 3 months to 18 years, operated between 2002 and 2004. Fourteen
      patients (36%) had laparotomy due to previous shunt operations and 5 patients
      (13%) due to other reasons. Laparoscopy was carried out concurrently with the
      cranial part of the procedure. In all cases, successful insertion of the
      peritoneal catheter was carried out with visual documentation of the patency of
      the distal catheter. There were no procedure-related complications. We recommend
      this minimally invasive procedure for all children with a body weight >5 kg,
      especially in cases of repeated shunt operations with intraperitoneal adhesions.

PMID- 16636617
TI  - Residual or recurrent cerebellar low-grade glioma in children after tumor
      resection: is re-treatment needed? A single center experience from 1983 to 2003.
AB  - PURPOSE: The aim of this study was to report on children with cerebellar low
      grade glioma (LGG), who were found to have progressive or nonprogresssive
      residual tumors or tumor recurrence after tumor resection. PATIENTS AND METHODS:
      Medical records and magnetic resonance imaging (MRI) studies of children (<16
      years) with cerebellar LGG were retrospectively analyzed. RESULTS: Of 289
      patients with CNS tumors referred between 1983 and 2003, 28 (9.7%) (15 male, 13
      female; median age at diagnosis: 71 months) had cerebellar LGG (pilocytic
      astrocytoma grade I: n = 21; fibrillary astrocytoma grade II: n = 5; mixed
      hamartoma/pilocytic astrocytoma: n = 1; radiographic diagnosis: n = 1). Total
      resection was initially performed in 16 patients (57.1%), near total resection in
      4 (14.3%), and partial resection in 6 patients (21.4%). One patient underwent
      biopsy. At a median follow-up of 112 months, 25 patients (89.3%) were alive, 18
      of them being in complete remission. Three patients died, 2 due to symptoms
      related to brain stem compression/infiltration and 1 patient due to postoperative
      cerebral edema. Presently 5 patients have nonprogressive residual tumors and 2
      patients developed nonprogressive recurrences 10 years and 20 months after
      initial total resection, respectively. None of them required second surgery and
      none received additional nonsurgical therapies. Only 1 additional patient had to
      undergo second surgery due to disease progression. CONCLUSIONS: A 'wait and see'
      strategy is justified in patients with nonprogressive recurrent or residual
      cerebellar LGG after primary tumor resection. However, long-term follow-up with
      repeated MRI is mandatory in these patients to detect disease progression. Second
      surgery is indicated only in patients with unequivocal disease progression, as
      documented by MRI.

PMID- 16636618
TI  - Seizure as a manifestation of intracranial hypotension in a shunted patient.
AB  - The authors describe a child with a ventriculo-peritoneal shunt in place for 5
      years who presented with 'postural' seizures (seizures on sitting upright, which
      resolved on recumbency). On shunt tap, the cerebrospinal fluid was obtained
      freely, but required gentle aspiration with a syringe in the recumbent position,
      suggesting very low intracranial pressure. Contrast magnetic resonance imaging
      showed pachymeningeal enhancement and enlargement of the pituitary gland
      diagnostic of intracranial hypotension along with well-decompressed ventricles.
      At the time of revision of the shunt, no evidence of malfunction was found and
      the valve was changed to one with a higher opening pressure. Following this, she
      became asymptomatic and seizure free. This case illustrates the fact that
      following shunting, intracranial hypotension may also predispose to seizures, and
      should be kept in mind while managing these patients.

PMID- 16636619
TI  - Pencil is mightier than the sword!
AB  - Penetrating injuries involving the spinal cord are not common. The incidence is,
      however, much higher in armed conflict. In a civilian population, gunshot wounds
      and stabbings account for the majority of such injuries. A pencil causing
      penetrating injury involving the spinal cord is very rare. We present the case of
      a young boy who accidentally suffered a penetrating injury involving the spinal
      cord from a pencil in his coat pocket.

PMID- 16636620
TI  - Frontal bone agenesis in a patient of spinal dysraphism.
AB  - Associated cranial abnormalities with spinal dysraphism are not uncommon. We came
      across an unusual case of a 1-year-old male child with spinal dysraphism having
      lumbar meningomyelocele, who also had split cord malformation (hemicord with
      intervening bony spur) with lipoma of one of the hemicord and filum terminale.
      The patient also had communicating hydrocephalus without Chiari malformation and
      also near-total frontal bone agenesis. Single photon emission computed tomography
      scanning of brain revealed normal perfusion. In the first stage of repair, the
      patient had postoperative CSF leak for which ventriculo-peritoneal shunt was
      performed. This constitutes a rare anomaly associated with spinal dysraphism.

PMID- 16636621
TI  - A case of Sotos syndrome with subduroperitoneal shunt.
AB  - The authors present a case of Sotos syndrome with increasing severity of subdural
      hygroma from the age of 5 months, which was managed with a subduroperitoneal
      shunt at 10 months of age. The patient had been followed up until 30 months of
      age with continuing improvement of symptoms. The patient initially presented with
      dolichocephaly accompanied by macrocrania, early tooth development, repeated
      pneumonia infections and developmental retardation concerning crawling, sitting,
      walking and speaking at 5 months of age. Magnetic resonance imaging (MRI)
      demonstrated partial hypoplasia of the corpus callosum and bifrontal subdural
      hygroma. The patient underwent subduroperitoneal shunting at 10 months of age
      with partial improvement of symptoms. At 18 months of age, the patient showed
      increased irritability and sweating, and development of spinal kyphosis, which
      resulted from shunt malfunction as shown in the shuntogram. The appearance of
      cervical syringomyelia was also seen in the MRI. After shunt revision, the
      irritability, sweating and kyphosis improved along with disappearance of the
      syringomyelia. The authors describe a case of Sotos syndrome with
      subduroperitoneal shunt that showed syringomyelia which developed with shunt
      malfunction but disappeared after shunt revision. We emphasize the importance of
      active management such as subduroperitoneal shunting to drain the cerebrospinal
      fluid in the Sotos syndrome.

PMID- 16636622
TI  - Spinal cord compression from spinal tuberculosis in a child.
AB  - Tuberculosis in children most frequently involves the pulmonary system. Spinal
      tuberculosis is very rare and insidious in children. We present a 1-year-old girl
      who was brought to our clinic with complaints of a bulge on her back and weakness
      in the feet. She was investigated with magnetic resonance imaging and at the
      thoracic level which revealed vertebral destruction and para- and perispinal
      abscess. Computed tomography of the lungs showed tuberculous lesions. The child's
      mother gave a post history of recovered lung tuberculosis. Due to appearance
      paraparesis secondary to vertebral destruction, we removed the abscess and
      infected bone and reconstruction was carried out with fibular allograft
      anteriorly. Tuberculosis bacilli were isolated from the postoperative biopsy
      culture. In this study, we evaluated the methods of diagnosis and treatment of
      spiral tuberculosis according to the studies and publications which have been
      done previously.

PMID- 16636623
TI  - Complete L1-L2 lateral dislocation without fracture and neurologic deficit in a
      child.
AB  - Spinal injuries in the infantile age group are relatively rare, mainly due to
      anatomical and biomechanical features of the pediatric spine. With its
      hypermobile character, pediatric spine can withstand trauma without fracture, and
      the elastic nature of the young spine allows easy slippage between segments,
      especially under the age of 8. Clinically, a few of the cases present with
      subluxation only, which seldom involve the lumbar level. We report an extremely
      rare case of traumatic complete upper lumbar lateral lystesis in a 3-year-old
      boy. The patient was treated conservatively and followed up for 2 years with some
      degree of correction.

PMID- 16636624
TI  - Atypical teratoid/rhabdoid tumor of the velum interpositum presenting as a
      spontaneous intraventricular hemorrhage in an infant: case report with long-term
      survival.
AB  - Atypical teratoid/rhabdoid tumors (ATRT) of infancy are highly malignant
      neoplasms that are most common in the first 2 years of life. We present the case
      of a 3-month-old girl who presented with the acute onset of generalized seizures
      and was found to have a large spontaneous intraventricular hemorrhage. The blood
      masked an underlying ATRT of the velum interpositum in the midline of the lateral
      ventricles and roof of the third ventricle, the first reported case in this
      location. Serial imaging studies and two ventriculoscopic biopsies were required
      to establish the diagnosis of the tumor in this unique location and in the midst
      of an evolving hematoma. After surgical resection, the patient received adjuvant
      chemotherapy. At 4-year follow-up, the child is neurologically intact, meeting
      normal developmental milestones, and imaging studies show no evidence of tumor.
      ATRT were previously associated with an extremely poor prognosis, but more recent
      evidence with complete surgical resection and adjuvant chemotherapy shows
      extended survival in some cases, supporting an aggressive and comprehensive
      approach to give these patients the best chance for a good outcome. Spontaneous
      brain hemorrhage in a full-term infant requires a diligent and persistent search
      to rule out an underlying neoplasm.

PMID- 16636625
TI  - Hydrocele of the canal of Nuck as a result of a rare ventriculoperitoneal shunt
      complication.
AB  - Patients with ventriculoperitoneal (VP) shunts may have multiple complications.
      Migration of the peritoneal catheter into some anatomical or congenitally open
      cavities can cause inguinal or genitourinary manifestations such as hernia,
      hydrocele or acute scrotum, and these are common in male infants. We report a
      very rare complication of VP shunt encountered in a female infant, manifesting as
      hydrocele of the canal of Nuck, the female counterpart of hydrocele of the
      spermatic cord. It is emphasized that VP shunts may also cause clinical inguinal
      manifestations in female infants, and groin or external genital organ swelling in
      these patients may be an important sign of shunt malfunction.

PMID- 16636626
TI  - Atypical traumatic craniocervical junction focal spinal subdural hematoma.
AB  - Spinal subdural hematoma (SSDH) is a rare entity and post-traumatic cervical SSDH
      is very rare. Review of the literature revealed 8 reported cases of traumatic
      SSDH and only 2 were cervical. The exact mechanism and pathogenesis of SSDHs are
      unclear. There are still controversies about the source of bleeding and
      mechanisms of formation of a hematoma. Here we report a case of a unique
      traumatic craniocervical junction focal subdural hematoma in an 8-year-old boy
      and discuss the possible mechanisms of SSDHs in trauma cases.

PMID- 16636627
TI  - Posttraumatic intradiploic pseudomeningocele: neuroimaging.

PMID- 16636628
TI  - Antipsychotic drugs: when and how to withdraw them?

PMID- 16636629
TI  - Current status of augmentation and combination treatments for major depressive
      disorder: a literature review and a proposal for a novel approach to improve
      practice.
AB  - Most patients with major depressive disorder (MDD) do not reach symptom
      remission. These patients with residual symptoms have worse function and worse
      prognosis than those who remit. Several augmentation and combination treatments
      are used to either increase the chances of achieving remission or to
      eliminate/minimize residual depressive symptoms. Evidence for these
      pharmacological approaches rests primarily on open, uncontrolled studies, and
      there are clearly not enough controlled studies. Clinicians should carefully
      weigh these different treatment options to increase their patients' chances of
      achieving and sustaining remission from depression. This paper will review the
      pertinent studies and will propose a novel approach to improve practice involving
      the use of augmentation or combination strategies at the outset of initial
      treatment to primarily enhance the chances of remission through synergy and/or a
      broader spectrum of action. This novel approach could potentially enhance
      retention and/or increase remission rates since the lack of response with
      antidepressant monotherapy may lead many depressed patients with little or no
      benefit to drop out of treatment, precluding the subsequent use of augmentation
      or combination strategies altogether. In addition, the emergence of certain side
      effects (e.g., agitation, insomnia) or the persistence of some initial baseline
      symptoms (e.g., anxiety, insomnia) may lead to premature discontinuation from
      monotherapy in the absence of concomitant use of augmenting pharmacological
      options targeting these symptoms.

PMID- 16636630
TI  - Financial ties between DSM-IV panel members and the pharmaceutical industry.
AB  - BACKGROUND: Increasing attention has been given to the transparency of potential
      conflicts of interest in clinical medicine and biomedical sciences, particularly
      in journal publishing and science advisory panels. The authors examined the
      degree and type of financial ties to the pharmaceutical industry of panel members
      responsible for revisions of the Diagnostic and Statistical Manual of Mental
      Disorders(DSM). METHODS: By using multimodal screening techniques the authors
      investigated the financial ties to the pharmaceutical industry of 170 panel
      members who contributed to the diagnostic criteria produced for the DSM-IV and
      the DSM-IV-TR. RESULTS: Of the 170 DSM panel members 95 (56%) had one or more
      financial associations with companies in the pharmaceutical industry. One hundred
      percent of the members of the panels on 'Mood Disorders' and 'Schizophrenia and
      Other Psychotic Disorders' had financial ties to drug companies. The leading
      categories of financial interest held by panel members were research funding
      (42%), consultancies (22%) and speakers bureau (16%). CONCLUSIONS: Our inquiry
      into the relationships between DSM panel members and the pharmaceutical industry
      demonstrates that there are strong financial ties between the industry and those
      who are responsible for developing and modifying the diagnostic criteria for
      mental illness. The connections are especially strong in those diagnostic areas
      where drugs are the first line of treatment for mental disorders. Full disclosure
      by DSM panel members of their financial relationships with for-profit entities
      that manufacture drugs used in the treatment of mental illness is recommended.

PMID- 16636631
TI  - Communication skills in psychiatry residents-- how do they handle patient
      concerns? An application of sequence analysis to interviews with simulated
      patients.
AB  - BACKGROUND: The main focus of the training of psychiatrists is on diagnosis and
      treatment based on the traditional doctor-centered approach to the psychiatric
      interview. Less attention is given to the correct handling of patients' emotional
      concerns, which is crucial for the patient-physician relationship, but also for
      improving diagnostic and treatment decisions. The aim of this study is to assess
      psychiatrists' responses to patients' concerns and worries. METHOD: 118
      consultations, conducted by 10 residents in psychiatry with 20 simulated
      patients, have been coded using the Verona Psychiatric Interview Classification
      System. Lag1 sequential analysis and a multinomial logit regression analysis were
      performed to investigate the relationship between patients' expressions of
      concern and psychiatrists' subsequent interventions in terms of patient-centered
      skills. RESULTS: Compared to doctor-centered interventions, all patients'
      expressions of concern increased the probability of passive listening (odds
      ratios between 2.4 and 4.2). They also increased the occurrence of emotion
      focusing interventions (odds ratios between 3.3 and 1.7), which however remained
      rare (4% of residents' total responses). A small although significant increase in
      the likelihood of active listening expressions was observed as a response to two
      types of patient expressions of concern: statements of feelings (odds ratio 1.4)
      and expression of opinions regarding problematic psychosocial issues (odds ratio
      of 1.7). CONCLUSIONS: Young psychiatrists are good passive listeners but need to
      improve active listening skills which, together with emotion focusing skills,
      should be a major learning target in psychiatry. These patient-centered
      interviewing skills should integrate those traditionally used for attributing ICD
      10 and/or DSM-IV categories.

PMID- 16636632
TI  - Prevalence of psychiatric disorders in an Italian town: low prevalence confirmed
      with two different interviews.
AB  - BACKGROUND: In Italy, few studies on the prevalence of psychiatric disorders have
      considered all of the most common disorders and very few have adopted the most
      common tools, that is, the Composite International Diagnostic Interview (CIDI)
      and the Present State Examination (PSE). The objective of the present study was
      to estimate the prevalence of psychiatric disorders and its correlates in the
      town of Jesi, Italy, using the PSE and CIDI, administered 7 years apart. METHODS:
      The two surveys were conducted among adults in Jesi (central Italy), using the
      PSE in 1993 and the CIDI in 2000. Participants were randomly chosen from the
      patient lists of general practitioners. RESULTS: The one-month prevalence of
      persons with a psychiatric disorder was 7.3% (95% CI: 4.4-11.6) in 1993 and 6.0%
      (95% CI: 3.5-9.5) in 2000. The lifetime and 1-year prevalence rates were 21.0 and
      8.2%, respectively. The most common disorders were depressive and anxiety
      disorders. Mood and anxiety disorders were more common among women and unmarried
      persons. CONCLUSIONS: The prevalence is lower than that in most other areas of
      the world yet consistent with estimates for Italian populations reported by
      studies using the same (or similar) tools.

PMID- 16636633
TI  - Can stress management at the workplace prevent depression? A randomized
      controlled trial.
AB  - BACKGROUND: Stress, mental health and depression at the workplace have emerged as
      common and significant problems. The effectiveness of a stress-management program
      at the workplace was investigated. METHODS: The effectiveness of a stress
      management program was examined in workers at a highly stressful workplace using
      a randomized controlled trial. The 58 workers in the office were randomly
      assigned into a stress-management group (n = 28) and a control group (n = 30).
      The stress-management program included lectures on the perception of stress,
      measures to cope with it, stress-management recording sheets, and e-mail
      counseling. This program was based on the cognitive behavioral approach. The
      stress-management program was carried out for 3 months, and perceived work
      related stress and psychological symptoms were evaluated using: General Health
      Questionnaire (GHQ)-30, Center for Epidemiologic Study for Depression (CES-D),
      the Questionnaire of Work-Related Stress and the Effort-Reward Imbalance
      Questionnaire. Twenty-one out of the 28 in the stress-management group and all in
      the control group were successfully followed up. RESULTS: In the stress
      management group, a significant improvement in the depressive symptoms was
      observed, compared with the control group in CES-D (p = 0.003 by two-tailed
      paired t-test, and p = 0.042 by repeated measure analysis of variance). In the
      multiple regression analysis, the effect of stress management on depressive
      symptoms at follow-up was significant (p = 0.041), controlling for potential
      confounding factors. However, the alleviation of perceived occupational stress
      was limited. CONCLUSIONS: A stress-management program based on the cognitive
      behavioral approach at the workplace may have potential for the prevention of
      depression.

PMID- 16636634
TI  - Quality of life and treatment outcome in panic disorder: cognitive behavior group
      therapy effects in patients refractory to medication treatment.
AB  - BACKGROUND: Improvements in quality of life (QoL) as well as symptomatic relief
      are important outcomes for the treatment of panic disorder (PD). The aim of this
      study is to assess the impact of brief cognitive behavior group therapy (CBGT)
      for panic disorder on QoL and to identify the clinical features associated with
      these changes. METHODS: Thirty-six patients with PD refractory to pharmacological
      treatment took part in a treatment protocol consisting of 12 sessions of CBGT. To
      evaluate the changes in QoL, the WHOQOL-bref was administered before and after
      treatment. RESULTS: Thirty-two patients completed the treatment. Significant
      improvement in all domains of QoL was observed (p< 0.001), which was associated
      with reductions in general and anticipatory anxiety (p = 0.018) and agoraphobic
      avoidance (p = 0.046). Consistent with previous findings, associations between
      QoL and panic-free status did not reach significance in this small study (p =
      0.094). CONCLUSIONS: CBGT was efficacious in the treatment of PD; the symptoms of
      anticipatory anxiety and avoidance appear to be more important than episodic
      panic episodes in affecting QoL.

PMID- 16636635
TI  - Persistent sexual side effects after SSRI discontinuation.

PMID- 16636636
TI  - Mindfulness-based cognitive therapy for persistent insomnia: a pilot study.

PMID- 16636637
TI  - F.M. Alexander technique in the treatment of stuttering-- a randomized single
      case intervention study with ambulatory monitoring.

PMID- 16636638
TI  - Evidence for a male or instead for a female depression?

PMID- 16636640
TI  - Cannabis-induced psychosis-like experiences are associated with high schizotypy.
AB  - OBJECTIVE: Recent studies have suggested that cannabis use is a risk factor for
      developing schizophrenia. We tested the hypothesis that cannabis use increases
      the likelihood of psychosis-like experiences in non-clinical participants who
      scored highly on a measure of schizotypy. METHOD: The psychological effects of
      cannabis were assessed in 137 healthy individuals (76% female, mean age 22 years)
      using a newly developed questionnaire concerned with subjective experiences of
      the drug: the Cannabis Experiences Questionnaire. The questionnaire has three
      subscales: Pleasurable Experiences, Psychosis-Like Experiences and After-Effects.
      Respondents also completed the brief Schizotypal Personality Questionnaire.
      RESULTS: Cannabis use was reported by 72% of the sample. Use per se was not
      significantly related to schizotypy. However, high scoring schizotypes were more
      likely to report both psychosis-like experiences and unpleasant after-effects
      associated with cannabis use. The pleasurable effects of cannabis use were not
      related to schizotypy score. CONCLUSION: High scoring schizotypes who use
      cannabis are more likely to experience psychosis-like phenomena at the time of
      use, and unpleasant after-effects. Our results are consistent with the hypothesis
      that cannabis use is a risk factor for full psychosis in this group.

PMID- 16636641
TI  - Conventional MRI is inadequate to delineate the relationship between the red
      nucleus and subthalamic nucleus in Parkinson's disease.
AB  - BACKGROUND: An understanding of the relationships between the anterior commissure
      posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus
      (RN) is imperative if these structures are to be used for targeting in deep brain
      stimulation. Currently, these relationships are incompletely understood and
      difficult to assess using conventional MRI. We examined the location and
      relationships of the STN and the RN to the AC-PC line and to each other in order
      to provide a greater understanding of their utility when targeting the STN, and
      the consistency of these anatomic relationships when examined using conventional
      MRI. METHODS: A total of 52 STN and RN in 26 patients with Parkinson's disease
      were evaluated on T2-weighted MR images. The anterior and posterior commissures
      and the border coordinates of the STN and RN were derived using frame
      coordinates. The distances from the midcommissural point (mcp) to the centers of
      the STN and RN, the diameters for each nucleus, and the distances between the
      nuclei were calculated in the x-, y-, and z-axes. RESULTS: The mean AC-PC length
      was 26.1 +/- 1.3 mm. The distance from the mcp to the center of the STN was 10 +/
      0.7 mm in the x-axis, 0.2 +/- 0.7 mm in the y-axis, and 3.3 +/- 0.9 mm in the z
      axis. The distance from the mcp to the center of the RN was 4.7 +/- 0.6 mm in the
      x-axis, -5.9 +/- 1.0 mm in the y-axis, and 6.1 +/- 1.3 mm in the z-axis. The
      distance between the STN and RN was 2.3 +/- 0.7 mm in the x-axis, 2.1 +/- 1.0 mm
      in the y-axis, and -0.2 +/- 1.3 mm in the z-axis. CONCLUSIONS: Although recent
      studies imply that the RN can be used as a relatively consistent marker for the
      position of the STN, the present data suggest otherwise. These data indicate that
      a single targeting method may be inadequate given the resolution of conventional
      MRI, and that it is imperative to use multiple anatomical measurements when
      targeting the STN for deep brain stimulation in Parkinson's disease.

PMID- 16636642
TI  - Stereotactic targeting of the ventrointermediate nucleus of the thalamus by
      direct visualization with high-field MRI.
AB  - OBJECTIVE: To evaluate the ability of high-field MRI to consistently produce high
      resolution, anatomical images of the thalamic ventrointermediate nucleus (Vim)
      suitable for stereotactic targeting. METHODS: MR images of the thalamus of
      patients treated for essential tremor were acquired prior to treatment using a 3
      tesla MR system. Similar images were acquired in 6 volunteers using, for
      comparison, both a 1.5-tesla and a 3.0-tesla system. RESULTS: The thalamic Vim
      was clearly and consistently delineated on the 3-tesla images. These images were
      successfully used for target localization in essential tremor patients. In the
      volunteers data, images acquired using the 1.5-tesla system were inferior to
      those acquired using the 3-tesla system, lacking the ability to consistently
      provide reliably defined borders of the Vim. CONCLUSION: 3-Tesla MRI can provide
      high-quality depiction of the Vim, potentially enabling accurate treatment
      planning by direct visualization and definition of the targeted Vim.

PMID- 16636643
TI  - A comparative study of most suitable miniplate fixation for mandibular symphysis
      fracture using a finite element model.
AB  - The purpose of this study is to determine the most stable fixation method for
      mandibular symphysis fractures by comparing the mechanical characteristics of
      models fixed at different positions with different numbers of plates. Fractures
      were generated in 3-dimensional finite element models, and were fixed with a
      single miniplate, parallel double miniplates, or perpendicular double miniplates.
      A 300 N perpendicular load was then applied on the left molar region, and a
      finite element analysis was performed. We compared vertical gaps between the
      fractured surfaces, maximum stress within the screw/plating system, and maximum
      stress around screw holes in the bone. Compared to the single miniplate, both the
      parallel and perpendicular double miniplates demonstrated significantly less
      stress in the screw/plating system and screw holes in the bone. In addition, the
      perpendicular double miniplateshad significantly smaller vertical gaps between
      fracture surfaces when compared to the single miniplate. Comparing parallel and
      perpendicular double miniplate fixations, less stress was found around the screw
      holes of the perpendicular miniplate models than those of the parallel
      miniplatemodels. There were no differences in vertical gaps or maximum stress
      within the screw/plating systems between the 2 double miniplate fixations. These
      results suggest that perpendicular double miniplate fixation is more suitable for
      fixing mandibular symphysis fractures.

PMID- 16636644
TI  - Anti-psychotics adherence among out-patients with schizophrenia in Hong Kong.
AB  - OBJECTIVE: Adherence to antipsychotic treatment is an important aspect of long
      term management of schizophrenia and other related psychotic disorders. The
      evaluation of adherence is often difficult in clinical settings. This study
      compared patients self-reports and clinician judgment of adherence behavior and
      explored their relationship with attitudes toward taking medication. METHODS:
      Clinician rated questionnaire and matching patient self rated questionnaires were
      administered to 508 consecutive outpatients and their clinicians in four hospital
      clinic sites in Hong Kong. Items in the questionnaires address adherence
      behaviors as well as attitudes toward medication. In addition, clinicians also
      estimate the presence of factors unfavorable to adherence such as substance
      abuse, cognitive impairments etc. RESULTS: Non-adherence was reported in at least
      26% of patients. Clinician's detection of non-adherence behaviors achieved
      relative high specificity (0.84) but has low sensitivity (0.33). A logistic
      regression analysis on patients' decision to stop medication revealed that
      significant predictors include patients' reported lack of perception from the
      benefits of medication, patients' reported negative feelings associated with
      regular medication and younger age. CONCLUSION: Non-adherence is a widespread
      phenomenon affecting a significant proportion of outpatients under treatment.
      Clinicians have relatively low sensitivity in detecting which patients are non
      adherent. Non-adherence behavior is predicted by level of awareness of illness,
      perceived benefits of medication, negative feelings toward medication and age.

PMID- 16636645
TI  - Economic evaluation of drug-eluting stents in Japan.
AB  - Stenting with a sirolimus-eluting stent (SES) dramatically reduces the risk of
      restenosis compared to bare metal stent (BMS) implantation. However, before SES
      can be widely adopted in clinical practice, it is essential to conduct an
      economic evaluation of this effective but expensive device. Our study was
      undertaken to estimate the three-year cumulative medical costs of stenting using
      SES compared to BMS. The data on clinical sequelae of stenting using BMS were
      derived from our previous study, based on data collected from three Japanese
      hospitals. We estimated that the probability of PTCA required for
      revascularization would be 0.224 times in SES implantation compared than in BMS
      implantation based on the SIRIUS study result. The medical costs for procedures
      were obtained from published articles and were adjusted to the March 2005 level.
      Our simulation showed the expected three-year cumulative medical cost per patient
      to be approximately 200,000 yen lower in the SES group(2,233,000 yen ) than in
      the BMS group (2,431,000 yen ). Sensitivity analyses with different presumptions
      confirmed that the economic advantage of SES over BMS was quite robust. We
      concluded that the use of SES would be a cost-saving option as compared with BMS
      implantation within the context of the Japanese healthcare system.

PMID- 16636646
TI  - Implant-supported anterior tooth restoration.
AB  - Various options are available for restoring anterior teeth. Their choice is
      dictated by the severity of infection of the teeth to be extracted and the pocket
      depth. Immediate single-stage implant placement proved to be the least traumatic
      option, which best preserved the soft tissue. A differential use of surgical and
      prosthodontic techniques is indispensable to account for conditions in the
      individual case. Given an adequate amount of hard tissue, soft tissue contours
      can be expected to return to normal. Immediate implants combined with a soft
      tissue support have been found to ensure that the depth of even larger pockets is
      stable for years.

PMID- 16636647
TI  - Compendium of animal rabies prevention and control, 2006: National Association of
      State Public Health Veterinarians, Inc. (NASPHV).
AB  - Rabies is a fatal viral zoonosis and a serious public health problem. The
      recommendations in this compendium serve as a basis for animal rabies prevention
      and control programs throughout the United States and facilitate standardization
      of procedures among jurisdictions, thereby contributing to an effective national
      rabies-control program. This document is reviewed annually and revised as
      necessary. These recommendations do not supersede state and local laws or
      requirements. Principles of rabies prevention and control are detailed in Part I;
      Part II contains recommendations for parenteral vaccination procedures; all
      animal rabies vaccines licensed by the United States Department of Agriculture
      (USDA) and marketed in the United States are listed in Part III.

PMID- 16636648
TI  - Proximal renal tubular acidosis and ocular pathology: a novel missense mutation
      in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
AB  - PURPOSE: The electrogenic Na+/HCO3- cotransporter (NBCe1) plays a major role in
      renal bicarbonate absorption via proximal tubules and therefore is crucial for
      maintaining normal blood pH. The human gene for NBCe1 (SLC4A4) produces two major
      transcripts by alternative promoter usage (kNBCe1, originally cloned from kidney
      and pNBCe1, pancreatic/general form). Though rare, recessive SLC4A4 mutations
      have been reported in patients with proximal renal tubular acidosis, short
      stature, and ocular pathology. A 27-year-old male presented with these findings.
      The purpose of this study was to investigate the molecular pathology responsible
      for this patient's clinical findings. METHODS: A comprehensive ophthalmic
      examination was performed, detailed ocular and systemic medical histories were
      taken and past medical records were obtained. Mutation screening was performed by
      using direct PCR sequencing of SLC4A4 exons and flanking intronic regions.
      Functional characterization of the mutation was made by expressing the wild-type
      and mutant NBCe1 proteins in Xenopus oocytes. RESULTS: We identified a novel,
      homozygous, missense SLC4A4 mutation (Leu522Pro in kNBCe1) in our patient who had
      pRTA, short stature, enamel hypoplasia, and bilateral ocular disease (cataract,
      glaucoma, and band keratopathy). The patient also had a medical history of
      ataxia, migraine with transient hemiparesis attacks, and slight hypothyroidism.
      The mutant RNA failed to induce electrogenic transport activity. The L522P
      protein was not effectively transported to the oocyte membrane and thus was
      unable to act as a transmembrane transporter. CONCLUSIONS: This novel mutation
      increases our understanding of the structural/functional aspects of the NBCe1
      protein and the molecular basis of the multiorgan pathologies associated with its
      defects.

PMID- 16636649
TI  - Expanding the mutational spectrum in TGFBI-linked corneal dystrophies:
      Identification of a novel and unusual mutation (Val113Ile) in a family with
      granular dystrophy.
AB  - PURPOSE: To report the clinical and molecular study of a family with an autosomal
      dominant stromal granular dystrophy of the cornea caused by a novel and unusual
      TGFBI gene mutation. METHODS: A complete ophthalmological examination, corneal
      dystrophy phenotype characterization, PCR amplification, and automated
      nucleotidic sequencing of exons 4, 11,12, 13, and 14 of the TGFBI gene was
      carried out on the family. DNA from 40 unrelated ethnically matched healthy
      individuals were analyzed as controls. RESULTS: Corneal dystrophy in two sisters
      was characterized by multiple grayish-white lesions located in the anterior and
      mid-stroma. Numerous small sized non-coalescent opacities were observed in the
      peripheral cornea while fewer larger lesions were apparent towards the central
      part of the cornea. A heterozygous missense mutation, consisting of a G to A
      transition at nucleotide position 384 in TGFBI exon 4 that predicts a valine
      (GTT) to isoleucine (ATT) replacement in residue 113 (Val113Ile) of the TGFBI
      protein was identified. CONCLUSIONS: This is the most 5' located mutation
      detected so far in subjects with TGFBI-linked corneal dystrophy. Valine 113 is
      strictly conserved in TGFBI from several species and we suggest that the
      phenotype observed in these patients is related to the unusual location of the
      mutation. Our results expand the mutational spectrum in the group of TGFBI-linked
      corneal dystrophies.

PMID- 16636650
TI  - Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a major mediator of
      angiogenesis, and nitric oxide (NO) is an upstream and downstream regulator of
      VEGF mediated angiogenesis. VEGF and NO have been suggested to play an important
      role in the pathogenesis of microvascular complications in diabetic retinopathy
      (DR). The objective of this study was to examine the genetic variations of the
      VEGF and eNOS gene and assess their possible relationship to DR in type 2
      diabetic patients in the Indian population. METHODS: In this study, 210 unrelated
      patients were enrolled and categorized into two study groups: a DR group,
      consisting of patients with proliferative diabetic retinopathy, and a diabetic
      without retinopathy (DWR) group comprised of patients with type 2 diabetes of
      more than 15 years duration who showed no signs of DR or had fewer than five dots
      or blot hemorrhages. Association of the genetic polymorphisms in the promoter and
      5' UTR region of VEGF and the intron4 region of eNOS were studied. Total genomic
      DNA was isolated from peripheral blood leukocytes. PCR-RFLP analysis was
      performed for all samples to evaluate the genotypes. The distributions of the
      genotypes were compared using the chi2 test. Haplotype estimation and multiple
      logistic regression analysis were carried out to analyze the significance of
      polymorphisms. RESULTS: We investigated four reported polymorphisms in the VEGF
      (5' UTR, promoter) and one reported polymorphism (intron 4) in the eNOS gene in
      Type 2 diabetes patients with (n=120) and without (n=90) retinopathy. The
      genotype distribution of the C(-7)T, T(-1498)C, and C(-634)G polymorphisms of
      VEGF differed significantly between patients with DR and DWR (p=0.001, p=0.0001,
      and p=0.021, respectively). Allele C in the -1498 region (p=0.0001) and T in -7
      region (p=0.002) were also found to be significantly increased in patients with
      retinopathy. Calculated odds ratios (OR) for three heterozygous genotypes of C(
      7)T, T(-1498)C, and C(-634)G regions were 4.17 (95% CI: 1.90-9.18, p=0.0001),
      4.37 (95% CI: 2.44-7.84, p=0.0001), and 2.33 (95% CI: 1.24-4.36, p=0.008),
      respectively, and was found to be significantly higher in the DR group when
      compared with the DWR group. Multiple logistic regression analysis revealed that
      the nongenetic parameters, age (p=0.024) and duration of diabetes (p=0.009), and
      the genetic parameters, like VEGF C(-7)T (p=0.002) and T(-1498)C (p=0.001)
      polymorphisms, were significantly associated with DR. The frequencies of
      haplotype consisting of the majority of alleles in VEGF were found to be
      significantly associated with DR. The genotype distribution of eNOS did not
      differ significantly between the two study groups, and therefore the eNOS intron
      4 polymorphism was considered to be less significant. CONCLUSIONS: This is the
      first study to report VEGF and eNOS gene polymorphisms in patients with DR in the
      Indian population. The data suggest that the polymorphisms in the 5' UTR and
      promoter region of VEGF could be regarded as a major genetic risk factor for DR.

PMID- 16636651
TI  - The role of metallothionein IIa in defending lens epithelial cells against
      cadmium and TBHP induced oxidative stress.
AB  - PURPOSE: Heavy metals and other forms of oxidative stress have been implicated as
      key factors in the formation of age-related cataract in humans. Metallothioneins
      are a group of proteins known to play important roles in defending cells against
      the cytotoxic effects of heavy metals. However, little is known about their
      involvement in defending against other forms of oxidative stress. Here, we
      examined the ability of metallothionein IIa (MTIIa) to protect human lens
      epithelial cells against cadmium and tertiary butyl hydroperoxide (TBHP)-induced
      oxidative stress. METHODS: MTIIa over-expressing human lens epithelial cells
      (SRA01/04) were created by retroviral mediated gene transfer. Normal and MTIIa
      over-expressing cells were exposed to various concentrations of cadmium and TBHP
      and subsequently monitored for cell death, changes in cell phenotype and
      differences in growth rate. In addition, expression levels of three other
      important antioxidant genes, heme oxygenase-1, thioredoxin reductase-1, and
      manganese superoxide dismutase were monitored by real-time RT-PCR following
      exposure to TBHP. RESULTS: Analysis of the over expressing cell lines revealed an
      approximate 3-4 fold increase in MTIIa expression relative to control cells,
      resulting in as much as 20% protection against cadmium-induced oxidative stress
      (p<0.001). The MTIIa over expressing cells were also significantly more resistant
      to TBHP treatment while control cells exhibited significant shrinking and
      rounding-up following 3-6 h TBHP treatment, no changes were observed in TBHP
      treated over expressing cells. When control cells were treated for 3 h or
      overnight with TBHP, 40-45% cell death occurred by day three. However, no cell
      death was observed at this time for the treated MTIIa over-expressing cell line.
      In addition, TBHP induced the expression of MTIIa, heme oxygenase-1, thioredoxin
      reductase-1, and MnSOD in both normal and MTIIa over-expressed cell lines.
      Interestingly the latter three genes were induced at 2-3 fold higher levels in
      TBHP-treated MTIIa over-expressing cells, compared to treated control cells
      (p=0.001, p=0.02, and p=0.01, respectively). CONCLUSIONS: These data indicate
      that over-expression of MTIIa in human lens epithelial cells results in
      protection against cadmium and TBHP-induced oxidative stress. In addition, the
      results suggest that MTIIa, and/or its ability to chelate metals, may play a role
      in regulating expression of other important antioxidant genes in response to
      oxidative stress.

PMID- 16636652
TI  - Identification of the genetic defect in the original Wagner syndrome family.
AB  - PURPOSE: The aim of the present study was to determine the genetic defect in
      Wagner syndrome, a rare disorder belonging to the group of hereditary
      vitreoretinal degenerations. This disease has been genetically mapped to
      chromosome 5q14.3. METHODS: Molecular analysis was performed in the progeny of
      the original pedigree described by Wagner in 1938. We searched for pathogenic
      mutations and their effects in two candidate genes, CSPG2 and EDIL3, which locate
      to the critical chromosomal interval. Reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis was used to investigate potential splice defects of
      CSPG2 transcripts. RESULTS: While no alterations were detected in the exons of
      EDIL3, several changes were identified in the CSPG2 gene. Only one of the novel
      changes, a heterozygous G to A substitution of the first nucleotide in intron 8,
      cosegregates with the disease phenotype. This change disrupts the highly
      conserved splice donor sequence. In blood cells of an index patient, we found
      CSPG2 transcripts with normally spliced exon 8/9 junction but also two additional
      CSPG2 transcripts, which were not detected in the control. One lacks the entire
      exon 8, while the other is missing only the last 21 bp of exon 8. CONCLUSIONS:
      CSPG2 encodes versican, a large proteoglycan, which is an extracellular matrix
      component of the human vitreous and participates in the formation of the vitreous
      gel. The splice site mutation described here may lead to a complete lack of exon
      8 in CSPG2 transcripts, which shortens the predicted protein by 1754 amino acids
      and leads to severe reduction of glycosaminoglycan attachment sites.

PMID- 16636653
TI  - Methylenetetrahydrofolatereductase (MTHFR) 677C>T polymorphism and open angle
      glaucoma.
AB  - PURPOSE: Increased plasma homocysteine levels have been found in patients with
      primary open angle glaucoma (POAG) and glaucoma secondary to pseudoexfoliation
      syndrome (PEXG). A common polymorphism of the methylenetetrahydrofolatereductase
      (MTHFR 677C>T) leads to moderately elevated plasma homocysteine levels
      particularly under conditions of impaired folate status. It was the aim of this
      study to investigate a hypothesized association between this polymorphism and the
      presence of either POAG or PEXG. METHODS: The present retrospective case-control
      study included a total of 553 participants comprising 204 patients with POAG, 138
      patients with PEXG, and 211 control subjects. Genotyping for the MTHFR 677C>T
      polymorphism was performed by polymerase chain reaction (PCR). RESULTS: No
      significant difference in the genotype distribution of the MTHFR 677C>T
      polymorphism was found between control subjects and patients with POAG or PEXG.
      The prevalence of the MTHFR 677TT genotype was 6.9% in patients with POAG, 11.6%
      in patients with PEXG, and 9.5% in control subjects. CONCLUSIONS: The present
      data suggest that the MTHFR 677C>T polymorphism itself is not a major genetic
      risk factor for POAG and PEXG in a central European population.

PMID- 16636654
TI  - Presymptomatic genetic diagnosis for consulters from a large Chinese family with
      juvenile open angle glaucoma.
AB  - PURPOSE: To provide genetic counseling and presymptomatic diagnosis to family
      members by investigating the genetic cause of a large primary juvenile open angle
      glaucoma (JOAG) pedigree with an autosomal dominant pattern. METHODS: Ocular
      examinations were performed on all members of the pedigree in order to determine
      their disease status. Subjects were labeled as affected individuals, unaffected
      individuals, and suspects. Genomic DNA was extracted from the peripheral blood of
      the family members. Three exons of MYOC, 12 coding exons of OPTN, and two coding
      exons of CYP1B1 were amplified by polymerase chain reaction (PCR). Direct DNA
      sequencing was used to identify mutations in MYOC, OPTN, and CYP1B1.
      Presymptomatic diagnoses were made for the consulters based on the results of
      both clinical examination and genetic analysis. RESULTS: One heterozygous
      mutation in the MYOC gene was identified in all patients of the pedigree. It was
      a cytosine to thymine transition at nucleotide 1,109, which corresponded to an
      amino acid residue change from proline to leucine at codon 370. The Pro370Leu
      mutation correlated with a severe JOAG phenotype as previously reported. Two
      adolescents, who were labeled as suspects, were detected to carry the same
      mutation and thus had a high risk of developing glaucoma. Close follow-up at
      regular intervals was recommended. In addition, no pathogenic mutations of OPTN
      and CYP1B1 were detected. CONCLUSIONS: The Pro370Leu mutation of the MYOC gene
      contributed to JOAG in this pedigree. Early onset, rapid development, poor
      response to medicine and high penetrance are characteristics of this mutation.
      Genetic analysis is valuable for providing genetic counseling and presymptomatic
      diagnosis to members in typical autosomal inheritance pedigrees with JOAG.

PMID- 16636655
TI  - The PITX3 gene in posterior polar congenital cataract in Australia.
AB  - PURPOSE: Congenital cataract is a significant cause of blindness worldwide. Many
      genes are known to cause the disorder. A large multigenerational pedigree was
      investigated for the genetic cause of a posterior polar autosomal dominant
      congenital cataract. METHODS: A genome wide scan was conducted in a large
      multigenerational family with autosomal dominant cataract to identify the linked
      region of the genome. The PITX3 gene was investigated through direct sequencing
      and detection of fluorescently labeled PCR products. RESULTS: Linkage was
      detected to a region of chromosome 10q23-26 which contains the candidate gene
      PITX3. A segregating 17 bp insertion mutation was identified. This mutation was
      not identified in 100 additional unrelated sporadic and familial congenital
      cataract patients. No mutations of the PITX3 gene were identified in 9 families
      with posterior polar congenital cataract. CONCLUSIONS: The 657ins17bp duplication
      of the PITX3 gene is the cause of the cataract phenotype in the large pedigree,
      however, this gene appears responsible for only a small proportion of congenital
      cataract in Australia.

PMID- 16636656
TI  - Protein expression in a transformed trabecular meshwork cell line: proteome
      analysis.
AB  - PURPOSE: Characterization of the human trabecular meshwork (TM) proteome is
      hindered by the small mass of intact tissue and the slow growth of cultured cell
      strains. We have previously characterized a transformed TM cell strain (GTM3)
      that demonstrates many of the same protein expression and cell signaling systems
      of nontransformed cell strains. The aim of this study was to initiate a proteomic
      survey of GTM3 cells as the initial step toward characterization of the complete
      human TM proteome. METHODS: GTM3 cells were cultured to confluence, harvested and
      solubilized in urea/Nonidet. The protein extract (600 mug) was focused in
      immobilized isoelectric focusing (IEF) strips, separated by 10% SDS PAGE, and
      visualized with colloidal Coomassie Blue. Spots of interest were excised,
      destained, and the contained proteins subjected to in-gel reduction,
      derivatization, and tryptic digestion. Tryptic peptides were extracted and
      analyzed by electrospray LC/MS/MS. Protein identification was made using the
      TurboSequest search algorithm and a recent version of the nonredundant human
      protein database downloaded from the National Center for Biotechnology
      Information (NCBI). RESULTS: Eighty-seven (87) primary proteins and 93 variants
      of these proteins were identified. A website was created (TM proteome) that
      combines data such as graphic spot location within the gel, peptide sequence,
      apparent and calculated pI, apparent and calculated mass, percentage of coverage,
      and protein informatic website links. CONCLUSIONS: Proteomic analysis of a
      transformed human TM cell line has been initiated combining preparative two
      dimensional PAGE separation, LC/MS/MS analysis of major proteins, and
      bioinformatic cataloging of the data. Further investigation of data from the
      transformed cell strain will be used in a comparative fashion for spot
      identification of analytical proteomic gels of human TM tissue and cultured
      normal cells. These initial data will form the base from which the
      characterization of protein expression in the normal and glaucomatous TM can be
      accomplished.

PMID- 16636657
TI  - A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the
      cause of disease.
AB  - PURPOSE: To report a large deletion that encompasses more than 90% of PRPF31 gene
      and two other neighboring genes in their entirety in an adRP pedigree that
      appears to show only the typical clinical features of retinitis pigmentosa.
      METHODS: To identify PRPF31 mutation in a dominant RP family (ADRP2) previously
      linked to the RP11 locus, the 14 exons of PRPF31 were screened for mutations by
      direct sequencing. To investigate the possibility of a large deletion,
      microsatellite markers near PRPF31 gene were analyzed by non-denaturing PAGE.
      RESULTS: Initial screening of PRPF31 gene in the ADRP2 family did not reveal an
      obvious mutation. A large deletion was however suspected due to lack of
      heterozygosity for nearly all PRPF31 intragenic single nucleotide polymorphysm
      (SNPs). In order to estimate the size of the deletion, SNPs and microsatellite
      markers spanning and flanking PRPF31 were analyzed in the entire ADRP2 family.
      Haplotype analysis with the above markers suggested a deletion of approximately
      30 kb that included the putative promoter region of a novel gene OSCAR, the
      entire genomic content of genes NDUFA3, TFPT and more than 90% of PRPF31 gene.
      Sequence analysis of the region flanking the potential deletion showed a high
      presence of Alu elements implicating Alu mediated recombination as the mechanism
      responsible for this event. CONCLUSIONS: This mutation provides evidence that
      haploinsufficiency rather than aberrant function of mutated proteins is the cause
      of disease in these adRP patients with mutations in PRPF31 gene.

PMID- 16636658
TI  - Mouse opsin promoter-directed Cre recombinase expression in transgenic mice.
AB  - PURPOSE: Gene inactivation with homologous recombination in mice is a widely used
      tool to study gene function. However, many proteins play essential roles in a
      number of tissues and germline gene inactivation often results in embryonic
      lethality. To overcome this limitation and to dissect the functions of essential
      genes beyond embryonic development, we generated mouse rod opsin promoter
      controlled cre transgenic mice with a goal of obtaining transgenic lines with a
      range of Cre activity in rod photoreceptors. METHODS: Transgenic mice expressing
      Cre recombinase directed by a long or short mouse opsin promoter were generated.
      Candidate Cre-expressing lines were identified with RT-PCR and Western blot
      analysis. Potentially useful Cre-expressing lines were characterized further with
      immunohistochemistry, PCR, and functional analysis using a Cre-activatable lacZ
      reporter mouse strain (R26R) to determine temporal and spatial patterns of Cre
      expression. Retinal function and morphology in these mouse lines were analyzed
      with electroretinography (ERG) and light microscopy of hematoxylin and eosin
      stained retinal sections. RESULTS: Transgenic mice expressing Cre in rod
      photoreceptors were generated. Characterization of candidate photoreceptor
      specific Cre mice using immunohistochemistry and functional assays demonstrated
      that an efficient Cre-mediated recombination occurred in rod photoreceptor cells
      in one mouse line and a mosaic Cre-mediated recombination occurred in rod
      photoreceptors and rod bipolar cells in another mouse line. Further analysis of
      these mice with ERG and morphological examination suggested that the retinas of
      eight-month-old adults were normal. CONCLUSIONS: We have generated transgenic
      mice expressing Cre recombinase in rod photoreceptors. One transgenic mouse line
      was capable of carrying out efficient Cre-mediated recombination in rod
      photoreceptors. Another transgenic mouse line was capable of carrying out mosaic
      Cre-mediated recombination in rod photoreceptors and bipolar cells across the
      whole retina. These mice will be useful tools for Cre/lox-based gene activation
      and inactivation, as well as genetic mosaics, in rod photoreceptors and rod
      bipolar cells.

PMID- 16636659
TI  - The gastrin gene promoter is regulated by p73 isoforms in tumor cells.
AB  - p73, a new p53 family member, is a transcription factor that is increasingly
      recognized in cancer research as an important player in tumorigenesis as well as
      in chemotherapeutic drug sensitivity. Despite the substantial structural and
      functional similarities to p53, accumulating evidence suggests that p53 and p73
      may differently regulate their transcriptional targets. In this study, we have
      investigated the role of p73 in regulation of the gastrin gene promoter. Gastrin
      is a peptide hormone and an important factor in determining the progression of a
      number of human malignancies. Our results show that p73 can bind to the gastrin
      promoter. This leads to transcriptional upregulation of gastrin mRNA. We also
      found that the levels of gastrin and p73 transcripts correlate in primary gastric
      tumors. Taken together, our results demonstrate a novel mechanism for regulation
      of gastrin gene transcription and support a concept that p53 and p73 may have
      different biological roles in tumors.

PMID- 16636660
TI  - The Drosophila homolog of the human tumor suppressor gene BHD interacts with the
      JAK-STAT and Dpp signaling pathways in regulating male germline stem cell
      maintenance.
AB  - Birt-Hogg-Dube syndrome (BHD) is a rare, inherited genodermatosis characterized
      by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD
      locus was mapped to chromosome 17p11.2 by linkage analysis, and germline
      mutations in a novel gene (BHD) were identified in a panel of BHD families. Using
      RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we
      have demonstrated that DBHD is required for male germline stem cell (GSC)
      maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC
      overproliferation phenotype associated with overexpression of either unpaired
      (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest
      that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and
      Dpp signal-transduction pathways. These findings suggest that the BHD protein may
      regulate tumorigenesis through modulating stem cells in human.

PMID- 16636661
TI  - Solution structure of the partially folded high-risk human papilloma virus 45
      oncoprotein E7.
AB  - The oncoprotein E7 of human papilloma viruses (HPV) is involved in the
      pathogenesis and maintenance of human cervical cancers. The most prevalent HPV
      types found in cervix carcinomas are HPV16, 18 and 45. The structure of the E7
      dimer from HPV45 (PDB 2F8B) was determined by nuclear magnetic resonance
      spectroscopy. Each monomer comprises an unfolded N-terminus and a well-structured
      C-terminal domain with a beta1beta2alpha1beta3alpha2 topology representing a
      unique zinc-binding fold found only for E7. Dimerization occurs through the
      alpha1/alpha1' helices and intermolecular beta-sheet formation but excludes the
      zinc-binding sites. E7 is reported to interact with a number of cellular proteins
      (e.g. pRb, p21(CIP1)). Binding of a peptide derived from the C-terminus of
      p21(CIP1) to the C-terminal domain of E7 was characterized by monitoring chemical
      shift perturbations of the amide groups of E7. This provides direct evidence that
      a shallow groove situated between alpha1 and beta1 of the E7 C-terminal domain is
      interacting with the C-terminus of p21(CIP1). Intriguingly, this binding site
      overlaps with the low-affinity binding site on E7 for the C-domain of pRb.

PMID- 16636662
TI  - CD44 ligation induces caspase-independent cell death via a novel calpain/AIF
      pathway in human erythroleukemia cells.
AB  - Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies
      (mAbs) has been shown to induce cell differentiation, cell growth inhibition and
      in some cases, apoptosis in myeloid leukemic cells. We report, herein, that
      exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in
      cell growth inhibition followed by caspase-independent apoptosis-like cell death.
      This process was associated with the disruption of mitochondrial membrane
      potential (Delta Psi m), the mitochondrial release of apoptosis-inducing factor
      (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these
      effects including cell death, loss of mitochondrial Delta Psi m and AIF release
      were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor
      isoquinoline. A significant protection against cell death was also observed by
      using small interfering RNA for AIF. Moreover, we show that calpain protease was
      activated before the appearance of apoptosis, and that calpain inhibitors or
      transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF
      release. These data suggest that CD44 ligation triggers a novel caspase
      independent cell death pathway via calpain-dependent AIF release in
      erythroleukemic HEL cells.

PMID- 16636663
TI  - Regulation of STAT3-mediated signaling by LMW-DSP2.
AB  - Signal transducer and activator of transcription 3 (STAT3), which mediates
      biological actions in many physiological processes, is activated by cytokines and
      growth factors, and has been reported to be constitutively activated in numerous
      cancer cells. In this study, we examined whether low molecular weight-dual
      specificity phosphatase two (LMW-DSP2) is involved in the regulation of the
      interleukin 6 (IL-6)/leukemia inhibitory factor (LIF)/STAT3-mediated signaling
      pathway. IL-6/LIF-induced LMW-DSP2 expression in murine testicular or hepatoma
      cell lines, while LMW-DSP2 overexpression in 293T cells suppressed IL-6-induced
      phosphorylation and activation of STAT3. Furthermore, LMW-DSP2 suppressed the
      expression of IL-6-induced endogenous genes. In contrast, small-interfering RNA
      mediated reduction of LMW-DSP2 expression enhanced IL-6-induced STAT3-dependent
      transcription. In fact, LMW-DSP2 interacted with STAT3 in vivo and endogenous LMW
      DSP2 bound to STAT3 in murine testicular GC-1 cells. These results strongly
      suggest that LMW-DSP2 acts as a negative regulator of the IL-6/LIF/STAT3-mediated
      signaling pathway.

PMID- 16636664
TI  - Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2
      ASK1 signals.
AB  - Human glutathione S-transferase P1-1 (GSTP1-1) is an ubiquitously expressed
      protein that plays an important role in the detoxification and xenobiotics
      metabolism. It has been shown that GSTP1-1 interacts with c-Jun NH(2)-terminal
      kinase (JNK) and suppresses its activity. Here, we report a novel function of
      GSTP1-1 in regulating tumor necrosis factor-alpha (TNF-alpha)-triggered
      signaling. The present experiments showed that GSTP1-1 physically associated with
      tumor necrosis factor receptor-associated factor 2 (TRAF2) in vivo and in vitro.
      Overexpression of GSTP1-1 inhibited TRAF2-induced activation of both JNK and p38
      but not of nuclear factor-kappaB (NF-kappaB). Glutathione S-transferase P1-1 also
      attenuated TRAF2-enhanced apoptosis signal-regulating kinase 1 (ASK1)
      autophosphorylation and inhibited TRAF2-ASK1-induced cell apoptosis by
      suppressing the interaction of TRAF2 and ASK1. Conversely, silencing of GSTP1-1
      expression through RNA interference (RNAi) resulted in increase of TNF-alpha
      dependent TRAF2-ASK1 association followed by hyper-activation of ASK1 and JNK. A
      mutant GSTP1-1 lacking TRAF domain-binding motif exhibited a significant decline
      of capacity to bind TRAF2 and block TRAF2-ASK1 signaling compared with the wild
      type of GSTP1-1. Moreover, the glutathione-conjugating activity of GSTP1-1 was
      not involved in the regulation of TRAF2 signaling. These findings indicate that
      GSTP1-1 plays an important regulatory role in TNF-alpha-induced signaling by
      forming ligand-binding interactions with TRAF2, which provides a new insight for
      analysing the protective effects of GSTP1-1 in tumor cells.

PMID- 16636665
TI  - Creation of tumorigenic human endometrial epithelial cells with intact
      chromosomes by introducing defined genetic elements.
AB  - Several genetic mutations have been identified in human endometrial cancers, but
      the specific combinations of mutations required to form endometrial cancer cells
      remain unknown. In the present study, we established an in vitro model of
      endometrial carcinogenesis, in which defined genetic elements were introduced
      into endometrial epithelial cells to create transformed endometrial cells at
      different stages. Introduction of the human papillomavirus type 16 E6/E7 gene and
      the human telomerase reverse transcriptase (hTERT) gene into human primary
      endometrial epithelial cells was sufficient to generate immortalized cells.
      Introduction of hTERT in early passages stabilized telomeres and created
      immortalized cells with normal karyotype, whereas introduction of hTERT in later
      passages generated immortalized cells but with widespread chromosome
      abnormalities. However, neither of those two immortalized cell lines exhibited
      tumorigenic phenotypes. Tumorigenic endometrial epithelial cells with invasive
      capacity were created by introducing a mutant K-ras allele into immortalized
      cells, keeping their chromosomes intact. Inhibiting the PTEN gene and activating
      Akt pathways did not create tumorigenic phenotypes, although the latter conferred
      anchorage-independent growth capacity. These findings suggest that neoplastic
      transformation of human endometrial cells can occur in the absence of widespread
      chromosomal abnormality, and that the combination of Rb inactivation, telomerase
      activation and altered K-ras signaling is sufficient for in vitro neoplastic
      transformation. The present experimental model can help clarify the genetic
      requirements for endometrial carcinogenesis, and it is useful for testing and
      developing specific inhibitors of specific oncogenic pathways.

PMID- 16636666
TI  - Furin regulates the intracellular activation and the uptake rate of cell surface
      associated MT1-MMP.
AB  - Invasion-promoting membrane type-1 matrix metalloproteinase (MT1-MMP) functions
      in cancer cells as an oncogene and as a mediator of proteolytic events on the
      cell surface. To exert its functional activity, MT1-MMP requires proteolytic
      removal of the prodomain sequence. There are two potential furin cleavage motifs,
      R(89)-R-P-R-C(93) and R(108)-R-K-R-Y(112), in the prodomain sequence of MT1-MMP.
      Our data suggest an important role of furin and related proprotein convertases
      (PCs) in mediating both the activation of MT1-MMP and the levels of functionally
      active MT1-MMP at the surface of cancer cells. We have determined that the
      peptide sequence that spans the first cleavage site is susceptible to furin and
      PC5/6, whereas the second sequence is susceptible to furin and also to PC5/6, PC7
      and PACE4. In the structure of the MT1-MMP proenzyme, the R(89)-R-P-R-C(93) site,
      however, is inaccessible to PCs. Our studies also demonstrated a direct
      functional link between the activation and the uptake rate of the proenzyme and
      the enzyme of MT1-MMP. Thus, the uptake rate of the latent MT1-MMP proenzyme
      noticeably exceeded that of the active enzyme. We conclude that furin and related
      PCs are the essential components of the specialized cellular machinery that
      controls the levels of the functionally active, mature, MT1-MMP enzyme on the
      cell surface to continually support the potency of pericellular proteolysis.

PMID- 16636667
TI  - ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF
      beta/Smad-induced growth arrest of prostate cells.
AB  - Transforming growth factor-beta (TGF-beta) elicits a potent growth inhibitory
      effect on many normal cells by binding to specific serine/threonine kinase
      receptors and activating specific Smad proteins, which regulate the expression of
      cell cycle genes, including the p21 cyclin-dependent kinase (CDK) inhibitor gene.
      Interestingly, cancer cells are often insensitive to the anti-mitogenic effects
      of TGF-beta for which the molecular mechanisms are not well understood. In this
      study, we found that the candidate prostate cancer susceptibility gene ELAC2
      potentiates TGF-beta/Smad-induced transcriptional responses. ELAC2 associates
      with activated Smad2; the C-terminal MH2 domain of Smad2 interacts with the N
      terminal region of ELAC2. Small interfering siRNA-mediated knock-down of ELAC2 in
      prostate cells suppressed TGF-beta-induced growth arrest. Moreover, ELAC2 was
      shown to specifically associate with the nuclear Smad2 partner, FAST-1 and to
      potentiate the interaction of activated Smad2 with transcription factor Sp1.
      Furthermore, activation of the p21 CDK inhibitor promoter by TGF-beta is
      potentiated by ELAC2. Taken together our data indicate an important
      transcriptional scaffold function for ELAC2 in TGF-beta/Smad signaling mediated
      growth arrest.

PMID- 16636668
TI  - High-resolution analysis of chromosome rearrangements on 8p in breast, colon and
      pancreatic cancer reveals a complex pattern of loss, gain and translocation.
AB  - The short arm of chromosome 8, 8p, is often rearranged in carcinomas, typically
      showing distal loss by unbalanced translocation. We analysed 8p rearrangements in
      48 breast, pancreatic and colon cancer cell lines by fluorescence in situ
      hybridization (FISH) and array comparative genomic hybridization, with a tiling
      path of 0.2 Mb resolution over 8p12 and 1 Mb resolution over chromosome 8.
      Selected breast lines (MDA-MB-134, MDA-MB-175, MDA-MB-361, T-47D and ZR-75-1)
      were analysed further. Most cell lines showed loss of 8p distal to a break that
      was between 31 Mb (5' to NRG1) and the centromere, but the translocations were
      accompanied by variable amplifications, deletions and inversions proximal to this
      break. The 8p12 translocation in T-47D was flanked by an inversion of 4 Mb, with
      a 100 kb deletion at the proximal end. The dicentric t(8;11) in ZR-75-1 carries
      multiple rearrangements including interstitial deletions, a triplicated
      translocation junction between NRG1 and a fragment of 11q (unconnected to CCND1),
      and two separate amplifications, of FGFR1 and CCND1 . We conclude that if there
      is a tumour suppressor gene on 8p it may be near 31 Mb, for example WRN; but the
      complexity of 8p rearrangements suggests that they target various genes proximal
      to 31 Mb including NRG1 and the amplicon centred around ZNF703/FLJ14299.

PMID- 16636669
TI  - TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide
      to trigger apoptosis.
AB  - We have previously shown that activation of the acid sphingomyelinase (ASM), the
      release of ceramide and the formation of ceramide-enriched membrane domains are
      central for the induction of apoptosis by CD95. Here, we demonstrate that tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95 activate the
      ASM via a redox mechanism resulting in release of ceramide and formation of
      ceramide-enriched membrane platforms. Ceramide-enriched membrane platforms serve
      to cluster DR5 upon stimulation. Antioxidants prevent TRAIL-mediated stimulation
      of ASM, the release of ceramide, the formation of ceramide-enriched membrane
      platforms and the induction of apoptosis by TRAIL. Further, ASM-deficient
      splenocytes fail to cluster DR5 in ceramide-enriched membrane domains upon TRAIL
      stimulation and resist TRAIL-induced apoptosis, events that were restored by
      addition of natural C(16)-ceramide. A dose-response analysis indicates that
      ceramide-enriched membrane platforms greatly sensitized tumor cells to TRAIL
      induced apoptosis. Our data indicate that ceramide-enriched membrane platforms
      are required for the signaling of TRAIL-DR5 complexes under physiological
      conditions.

PMID- 16636670
TI  - Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells.
AB  - Microarray RNA gene expression profiling analysis has shown that Sox4 (Sry
      related high mobility group (HMG) box 4) is one of the most upregulated genes in
      adenoid cystic carcinoma (ACC), relative to non-neoplastic tissue of origin.
      Here, we show that Sox4 protein is similarly upregulated in ACC by
      immunohistochemistry of 28 primary cancers and 20 normal tissues. To elucidate
      the functional significance of these findings, RNA interference (RNAi)-mediated
      RNA silencing was used to downregulate Sox4 expression in the ACC-derived cell
      line, ACC3. With confirmed knockdown of Sox4 protein, cell viability was reduced
      by 51%, with a corresponding increase of apoptosis to 85% as compared to 12% in
      controls. Apoptosis was confirmed by cell morphology, DNA fragmentation and flow
      cytometry. Cells could be rescued from the proapoptotic effects of Sox4 RNAi by
      co-transfection with a construct expressing functional Sox4. Microarray gene
      expression profiling of RNAi knockdown experiments shows that downregulation of
      Sox4-modulated expression of critical genes involved in apoptosis and cell cycle
      control. Overall, our findings suggest that Sox4 contributes to the malignant
      phenotype of ACC cells by promoting cell survival.

PMID- 16636671
TI  - Identification of an ataxia telangiectasia-mutated protein mediated surveillance
      system to regulate Bcl-2 overexpression.
AB  - Bcl-2 can both promote and attenuate tumorigenesis. Although the former function
      is relatively well characterized, the mechanism of the latter remains elusive. We
      report here that enforced Bcl-2 expression in MCF7 cells stabilizes p53, induces
      phosphorylation of p53 serine 15 (p53pSer15) and inhibits MCF7 cell growth.
      Consistent with p53 Ser15 being a target of ataxia telangiectasia mutated
      protein(ATM)/ATR (ATM- and rad3-related) in the DNA damage response, Bcl-2
      activates ATM by inducing ATM Ser1981 phosphorylation, which is accompanied with
      the phosphorylaton of two additional ATM substrates, Chk2 Thr68 and H2AX Ser139.
      Downregulation of ATM using a specific small interference RNA fragment (ATMRNAi)
      abolished Bcl-2-induced p53pSer15 and Bcl-2-mediated growth inhibition of MCF7
      cells. Ectopic expression of a dominant-negative p53 mutant, p53175H, partially
      rescued this growth inhibition. Taken together, these observations demonstrate
      the contribution of ATM-p53 function to Bcl-2-mediated inhibition of MCF7 cell
      growth, indicating an ATM-mediated surveillance system for regulating Bcl-2
      overexpression. Consistent with this concept, we found that MCF7 cells express
      Bcl-2 heterogeneously with 34.5% of cells being Bcl-2 negative. In general, Bcl-2
      positive MCF7 cells proliferate slower than those of Bcl-2 negative. Thus, we
      provide evidence suggesting that activation of ATM suppresses Bcl-2-induced
      tumorigenesis, and that attenuation of ATM function may be an important event in
      breast cancer progression.

PMID- 16636672
TI  - Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced
      cell transformation by controlling Src activation.
AB  - Epidermal growth factor receptor (EGFR) and Src tyrosine kinase cooperate in
      regulating EGFR-mediated cell signaling and promoting cell transformation and
      tumorigenesis in pathological conditions. Activation of Src is tightly regulated
      by the C-terminal Src kinase (Csk). The Csk-binding protein (Cbp) is a
      ubiquitously expressed transmembrane protein. Its functions include suppression
      of T-cell receptor activation through recruiting Csk and inhibiting Src family
      kinase (SFK). However, a potential role of Cbp in EGF-induced cell activities has
      not been investigated. Here, we report that EGF-stimulation-induced Cbp tyrosine
      phosphorylation followed by Cbp-Csk association, in a SFK-dependent manner.
      Expression of wild-type (wt) Cbp remarkably suppressed EGF-induced activation of
      Src, ERK1/2, and Akt-1 enzymes, and NIH3T3 cell transformation, as well as colony
      formation of a breast cancer cell line (MDA-MB-468) in soft agar. In contrast,
      expression of CbpY317F or knockdown endogenous Cbp in NIH3T3 cells by RNA
      interference significantly enhanced EGF-induced activation of these enzymes and
      cell transformation. In addition, overexpression of multiple receptor tyrosine
      kinases (RTKs)-induced Cbp tyrosine phosphorylation. These results demonstrate
      that Cbp functions as a negative regulator of cell transformation and tumor cell
      growth through downregulation of Src activation, suggesting that Cbp might be
      broadly involved in RTKs-activated signaling pathways and tumorigenesis.

PMID- 16636673
TI  - Two-hit model for progression of medulloblastoma preneoplasia in Patched
      heterozygous mice.
AB  - Inactivation of one Ptc1 allele predisposes humans and mice to spontaneous
      medulloblastoma development, and irradiation of newborn Ptc1 heterozygous mice
      results in dramatic increase of medulloblastoma incidence. While a role for loss
      of wild-type (wt) Ptc1 (LOH) in radiation-induced medulloblastomas from
      Ptc1(neo67/+) mice is well established, the importance of this event in
      spontaneous medulloblastomas is still unclear. Here, we demonstrate that
      biallelic Ptc1 loss plays a crucial role in spontaneous medulloblastomas, as
      shown by high rate of wt Ptc1 loss in spontaneous tumors. In addition, remarkable
      differences in chromosomal events involving the Ptc1 locus in spontaneous and
      radiation-induced medulloblastomas suggest distinct mechanisms for Ptc1 loss. To
      assess when, during tumorigenesis, Ptc1 loss occurs, we characterized cerebellar
      abnormalities that precede tumor appearance in Ptc1(neo67/+) mice. We show that
      inactivation of only one copy of Ptc1 is sufficient to give rise to abnormal
      cerebellar proliferations with different degree of altered cell morphology, but
      lacking potential to progress to neoplasia. Furthermore, we identify biallelic
      Ptc1 loss as the event causally related to the transition from the preneoplastic
      stage to full blown medulloblastoma. These results underscore the utility of the
      Ptc1(neo67/+) mouse model for studies on the mechanisms of medulloblastoma and
      for development of new therapeutic strategies.

PMID- 16636674
TI  - AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast
      carcinoma cells.
AB  - Activating enhancer-binding protein 2alpha (AP-2alpha) and activating enhancer
      binding protein 2gamma (AP-2gamma) are transcription factors that bind GC-rich
      consensus sequences and regulate the expression of many downstream genes. AP
      2alpha and AP-2gamma interact with p53 both physically and functionally.
      Expression microarray results in human breast carcinoma cells with forced p53
      expression revealed AP-2gamma as a putative transcriptional target of p53. To
      confirm and extend these findings we measured the effects of forced p53
      expression in human breast carcinoma cells by real-time reverse transcription
      PCR, Western blotting, electrophoretic gel mobility shift assays, promoter
      reporter, chromatin immunoprecipitation and chromatin accessibility assays. Wild
      type p53 expression rapidly induced not only AP-2gamma but also AP-2alpha mRNA.
      The subsequent increase in these proteins led to increased AP-2 DNA-binding and
      transactivating activity. Candidate p53-binding sites were identified in the AP
      2alpha and AP-2gamma promoters. p53 binding to these cis-elements in vivo was
      also observed, together with a relaxation of chromatin structure in these
      regions. Finally, expression of either AP-2alpha or gamma inhibited growth of
      human breast carcinoma cells in vitro. Taken together, our findings indicate that
      these AP-2 genes are targets for transcriptional activation by p53 and suggest
      that AP-2 proteins may mediate some of the downstream effects of p53 expression
      such as inhibition of proliferation.

PMID- 16636675
TI  - BARX2 and estrogen receptor-alpha (ESR1) coordinately regulate the production of
      alternatively spliced ESR1 isoforms and control breast cancer cell growth and
      invasion.
AB  - The estrogen receptor-alpha gene (ESR1) was previously identified as a direct
      target of the homeobox transcription factor BARX2 in MCF7 cells. Here, we show
      that BARX2 and ESR1 proteins bind to different ESR1 gene promoters and regulate
      the expression of alternatively spliced mRNAs that encode 66 and 46 kDa ESR1
      protein isoforms. BARX2 increases the expression of both ESR1 isoforms; however,
      it has a greater effect on the 46 kDa isoform, leading to an increased ratio
      between the 46 and 66 kDa proteins. BARX2 also influences estrogen-dependent
      processes such as anchorage-independent growth and modulates the expression of
      the estrogen-responsive genes SOX5, RBM15, Dynein and Mortalin. In addition,
      BARX2 expression promotes cellular invasion and increases the expression of
      active matrix metalloproteinase-9 (MMP9). BARX2 also increases the expression of
      the tissue inhibitor of metalloproteinase (TIMP) genes, TIMP1 and TIMP3, in
      cooperation with estrogen signaling. Overall, these data indicate that BARX2 and
      ESR1 may coordinately regulate cell growth, survival and invasion pathways that
      are critical to breast cancer progression.

PMID- 16636676
TI  - Inhibition of medulloblastoma cell invasion by Slit.
AB  - Invasion of brain tumor cells has made primary malignant brain neoplasms among
      the most recalcitrant to therapeutic strategies. We tested whether the secreted
      protein Slit2, which guides the projection of axons and developing neurons, could
      modulate brain tumor cell invasion. Slit2 inhibited the invasion of
      medulloblastoma cells in a variety of in vitro models. The effect of Slit2 was
      inhibited by the Robo ectodomain. Time-lapse videomicroscopy indicated that Slit2
      reduced medulloblastoma invasion rate without affecting cell direction or
      proliferation. Both medulloblastoma and glioma tumors express Robo1 and Slit2,
      but only medulloblastoma invasion is inhibited by recombinant Slit2 protein.
      Downregulation of activated Cdc42 may contribute to this differential response.
      Our findings reinforce the concept that neurodevelopmental cues such as Slit2 may
      provide insights into brain tumor invasion.

PMID- 16636677
TI  - SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B
      lymphoblastic leukemia and B-cell lymphoma cells.
AB  - Perpetual V(D)J recombinase activity involving multiple DNA double-strand break
      events in B-cell lineage leukemia and lymphoma cells may introduce secondary
      genetic aberrations leading towards malignant progression. Here, we investigated
      defective negative feedback signaling through the (pre-) B-cell receptor as a
      possible reason for deregulated V(D)J recombinase activity in B-cell malignancy.
      On studying 28 cases of pre-B-lymphoblastic leukemia and 27 B-cell lymphomas,
      expression of the (pre-) B-cell receptor-related linker molecule SLP65 (SH2
      domain-containing lymphocyte protein of 65 kDa) was found to be defective in
      seven and five cases, respectively. SLP65 deficiency correlates with RAG1/2
      expression and unremitting V(H) gene rearrangement activity. Reconstitution of
      SLP65 expression in SLP65-deficient leukemia and lymphoma cells results in
      downregulation of RAG1/2 expression and prevents both de novo V(H)-DJ(H)
      rearrangements and secondary V(H) replacement. We conclude that iterative V(H)
      gene rearrangement represents a frequent feature in B-lymphoid malignancy, which
      can be attributed to SLP65 deficiency in many cases.

PMID- 16636678
TI  - Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies
      HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose
      dependent growth delay in vivo.
AB  - We and others have demonstrated already that TRAIL (TNF-related apoptosis
      inducing ligand) is a very promising candidate for molecular targeted anticancer
      therapy, especially when combined with ionizing radiation or other DNA-damaging
      agents. Agonist monoclonal antibodies that activate and are specific for the
      death signaling TRAIL receptors are an alternative method to stimulate the
      programmed cell death pathway. Phase 1 clinical trials have subsequently been
      conducted and shown a very good tolerability of these antibodies. In order to
      assess the efficacy of TRAIL receptor stimulation to induce cell death by this
      alternate method, we studied the combination of the agonistic-TRAIL receptor
      antibodies HGS-ETR1 and HGS-ETR2 with radiation in vitro and in vivo. Induction
      of apoptosis after combined treatment with TRAIL receptor antibodies HGS-ETR1
      and/or HGS-ETR2 (0.01, 0.1, 1.0 mg/ml) and irradiation with 2, 5 or 10 Gy was
      determined by fluorescence microscopy and Western blot analysis of caspase-8 and
      PARP. The colorectal tumour cell lines Colo 205, HCT 116 and HCT-15 were used for
      in vitro experiments. Growth delay experiments were performed with combined
      treatment with fractionated irradiation (days 1-5 and 3 Gy single dose/day) and
      the receptor antibodies (intraperitonially, three different concentrations,
      application on days 1, 4 and 8) on Colo 205 xenograft-bearing NMRI (nu/nu) nude
      mice. HGS-ETR1 and HGS-ETR2 induced apoptotic cell death in a dose-dependent
      fashion and significantly increased cell death in combination with irradiation in
      vitro when compared to either irradiation or antibody treatment alone. The
      efficacy of the combined treatment seems to be at least partially Bax-dependent.
      Similar to the results from cell culture experiments, in vivo experiments
      demonstrated a dose-dependent delay in tumour growth after combined treatment. In
      vivo, in the Colo205 xenograft model, HGS-ETR2 revealed a higher activity than
      HGS-ETR1. This is the first study to demonstrate significant efficacy of combined
      treatment with the monoclonal agonistic TRAIL receptor antibodies HGS-ETR1 and
      HGS-ETR2 and ionising radiation in in vitro and in vivo models. We postulate that
      HGS-ETR1 and HGS-ETR2 will be very promising new agents in the field of molecular
      targeted multi-modality anticancer therapy.

PMID- 16636679
TI  - Androgen receptor mutation (T877A) promotes prostate cancer cell growth and cell
      survival.
AB  - Alteration of the AR functions due to amplification, overexpression and somatic
      mutation of the AR itself or altered interaction of AR with other cell growth
      regulatory proteins, may contribute to a significant subset of advanced prostate
      cancer (CaP). Very little is known about the pathways impacted by AR
      dysfunctions, although CaP associated AR alterations suggest the biological role
      of the AR dysfunction in disease progression. Comparative evaluations of wild
      type (wt) AR and mutant (mt) ARs in appropriate experimental models should
      provide a better understanding of the functional impact of AR alterations in CaP.
      Here, we provide direct evidence showing cell growth/cell survival promoting
      effects of the widely studied CaP associated AR mutation (T877A). In contrast to
      Ad-wtAR or Ad-control infected LNCaP or LAPC4 cells, Ad-mtAR (T877A) infected
      LNCaP or LAPC4 cells continued to grow in the androgen-deprived medium and
      exhibited an androgen independent AR-transcription factor activity. Further, Ad
      mtAR (T877A) infected LNCaP or LAPC4 cells exhibited enhanced cell growth in the
      presence of lower concentrations of the synthetic androgen, R1881. Of note, Ad
      mtAR (T877A) infected LNCaP cells showed striking resistance to cell growth
      inhibition/apoptosis mediated by the wt p53. Taken together, these findings
      provide novel insights into the AR dysfunctions resulting from the T877A mutation
      and functionally similar AR alterations may provide selective cell
      growth/survival advantage for CaP progression. These observations have important
      implications for developing biology-based prognostic biomarkers and therapeutic
      strategies for CaP showing such AR dysfunctions.

PMID- 16636680
TI  - Nuclear BCL-10 expression is common in lymphoplasmacytic lymphoma/Waldenstrom
      macroglobulinemia and does not correlate with p65 NF-kappaB activation.
AB  - B-cell lymphoma 10 (BCL-10) is expressed in the cytoplasm of normal germinal
      center and marginal zone B-cells and is involved in lymphocyte development and
      activation. Aberrant nuclear expression of BCL-10 occurs in a subset of
      extranodal marginal zone B-cell lymphomas (MALT lymphomas), primarily those with
      the t(1;14)(p22;q32) or t(11;18)(q21;q21). Little is known about BCL-10
      expression in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM).
      We assessed for BCL-10 in 51 bone marrow (BM) specimens involved by LPL/WM using
      immunohistochemical methods. All patients had monoclonal IgM in serum. Extent of
      BM involvement was assessed using PAX-5/BSAP and CD20 immunostains and the
      pattern and percentage of B-cells positive for BCL-10 was determined. The p65
      subunit of nuclear factor-kappa B (NF-kappaB), a molecule downstream of BCL-10,
      was also assessed immunohistochemically. Nuclear BCL-10 staining was present in
      28/51 (55%) specimens. BCL-10 expression correlated with greater extent of BM
      involvement (P=0.001), but did not correlate with serum IgM paraprotein levels,
      type of immunoglobulin light chain, or clinical variables. Nuclear expression of
      the p65 subunit of NF-kappaB was detected in 17/50 (34%) specimens, suggesting
      that NF-kappaB is active in a subset of LPL/WM. p65 NF-kappaB activation did not
      correlate with nuclear BCL-10 immunostaining. Cytogenetic analysis in 29 cases
      showed no evidence of the t(1;14) or t(11;18). These results indicate that
      nuclear BCL-10 expression is common in LPL/WM and does not correlate with MALT
      lymphoma-associated translocations or p65 NF-kappaB nuclear staining.

PMID- 16636681
TI  - MEK/ERK signaling is a critical mediator for integrin-induced cell scattering in
      highly metastatic hepatocellular carcinoma cells.
AB  - The human hepatocellular carcinoma (HCC)-derived cell line KYN-2 is thought to
      provide a good model for studying the molecular basis of invasion and metastasis
      of human HCC, because it often shows cell scattering in vitro and intrahepatic
      metastasis in vivo. We previously found that integrin-mediated extracellular
      signals inactivated E-cadherin in KYN-2, and caused loss of cell-cell contact
      with gain of cell motility, which is considered to be a critical step in the
      process of cancer cell invasion and metastasis. To further understand molecular
      mechanisms involved in biological aggressiveness of HCC, we investigated
      intracellular signaling involved in integrin-mediated scattering of KYN-2 cells.
      Cultured KYN-2 cells formed trabecular aggregates in suspension, but when
      adhering to integrin-stimulating substrata, they scattered according to
      phosphorylation of extracellular signal-regulated kinase (ERK). Upon treatment
      with ERK kinase (MEK) inhibitor PD98059, adhered KYN-2 cell scattering was
      inhibited, tight cell-to-cell contact was recovered, and both E-cadherin and
      actin filaments accumulated in the area of intercellular contact zone. In
      contrast, constitutively active MEK1-transfected KYN-2 cells showed reduced E
      cadherin and actin filaments in the intercellular contact zone, showing a
      flattened phenotype with broad lamellipodia. Enforced signaling of MEK-ERK
      pathway in KYN-2 cells suppressed cadherin-mediated homotypic adhesion and
      increased the potential of cell motility. An antibody-based protein microarray
      analysis revealed that the cytoplasmic protein c-Cbl was significantly
      downregulated in MEK1-transfected KYN-2 cells, suggesting that c-Cbl might be a
      candidate downstream mediator of integrin/MEK/ERK-mediated cell scattering. In
      conclusion, cell scattering of the highly metastatic cell line KYN-2 is regulated
      through the integrin-MEK-ERK signaling cascade, suggesting that this molecular
      pathway may be critical in intrahepatic metastasis of human HCC.

PMID- 16636683
TI  - Pharmacogenetics of the human beta-adrenergic receptors.
AB  - The beta-adrenergic receptors (ADRBs) are cell surface receptors that play
      central roles in the sympathetic nervous system. Pharmacological targeting of two
      of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic
      approach for common and important diseases including asthma, hypertension and
      heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both
      in vitro and clinical disease phenotypes. More recently, interest has shifted to
      studies that explore potential interaction between variation in ADRBs and
      medications directed at these important receptors. This paper reviews the current
      state of knowledge and understanding of ADRB genetic variation and explores the
      likely direction of future studies in this area.

PMID- 16636684
TI  - Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic
      phospholipase A2 in rat frontal cortex.
AB  - Chronic lithium and carbamazepine, which are effective against mania in bipolar
      disorder, decrease the activity of cytosolic phospholipase A(2) (cPLA(2)) and the
      turnover rate of arachidonic acid in phospholipids in rat brain. Assuming that
      stages of bipolar disorder are related to brain arachidonic acid metabolism, we
      hypothesized that drugs effective in depression would increase cPLA(2) activity.
      To test this hypothesis, adult male CDF-344 rats were administered fluoxetine (10
      mg/kg intraperitoneally (i.p.) or saline (control) (i.p.) chronically for 21
      days. Frontal cortex cPLA(2) protein, phosphorylated cPLA(2), activity and mRNA
      levels were increased after chronic fluoxetine. Transcription factors (activator
      protein-1, activator protein-2, glucocorticoid response element, polyoma enhancer
      element-3 and nuclear factor-kappa B) that are known to regulate cPLA(2) gene
      expression were not significantly changed by chronic fluoxetine, but nuclear AU
      rich element/poly(U)-binding/degradation factor-1 RNA-stabilizing protein was
      increased significantly. The results suggest that chronic fluoxetine increases
      brain cPLA(2) gene expression post-transcriptionally by increasing cPLA(2) mRNA
      stabilization. Chronic fluoxetine's effect on cPLA(2) expression was opposite to
      the effect reported with chronic lithium or carbamazepine administration, and may
      be part of fluoxetine's mode of action.

PMID- 16636682
TI  - Mitochondrial-related gene expression changes are sensitive to agonal-pH state:
      implications for brain disorders.
AB  - Mitochondrial defects in gene expression have been implicated in the
      pathophysiology of bipolar disorder and schizophrenia. We have now contrasted
      control brains with low pH versus high pH and showed that 28% of genes in
      mitochondrial-related pathways meet criteria for differential expression. A
      majority of genes in the mitochondrial, chaperone and proteasome pathways of
      nuclear DNA-encoded gene expression were decreased with decreased brain pH,
      whereas a majority of genes in the apoptotic and reactive oxygen stress pathways
      showed an increased gene expression with a decreased brain pH. There was a
      significant increase in mitochondrial DNA copy number and mitochondrial DNA gene
      expression with increased agonal duration. To minimize effects of agonal-pH state
      on mood disorder comparisons, two classic approaches were used, removing all
      subjects with low pH and agonal factors from analysis, or grouping low and high
      pH as a separate variable. Three groups of potential candidate genes emerged that
      may be mood disorder related: (a) genes that showed no sensitivity to pH but were
      differentially expressed in bipolar disorder or major depressive disorder; (b)
      genes that were altered by agonal-pH in one direction but altered in mood
      disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH
      sensitivity that displayed the same direction of changes in mood disorder. Genes
      from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The
      interpretation of postmortem brain studies involving broad mitochondrial gene
      expression and related pathway alterations must be monitored against the strong
      effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could
      present a starting point for candidate gene search in neuropsychiatric disorders.

PMID- 16636685
TI  - CYP2A7 polymorphic alleles confound the genotyping of CYP2A6*4A allele.
AB  - Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine. Genetic
      polymorphisms of CYP2A6 contribute to the interindividual variability of nicotine
      metabolism. We encountered some subjects possessing two copies of the CYP2A6
      gene, although they were genotyped as heterozygotes of the CYP2A6*4A allele
      (entire CYP2A6 gene deleted allele). From the subjects, we found CYP2A7
      polymorphic alleles (CYP2A7*1B, CYP2A7*1C, and CYP2A7*1D) in which the sequences
      in the 3'-flanking region were converted to the corresponding CYP2A6 sequences,
      being confused with the CYP2A6*4A. These allele frequencies in European-Americans
      (n=187) were 1.3, 2.1, 0.3%, respectively, but these were very rare in African
      Americans (n=176), Japanese (n=184), and Koreans (n=209). By an improved
      genotyping method, the allele frequency of CYP2A6*4A of 3.7% in European
      Americans was corrected to 0%. The comprehensible and reliable genotyping method
      developed in this study would be useful to evaluate associations between the
      genotype and phenotype.

PMID- 16636686
TI  - Physiological effects of lower extremity functional electrical stimulation in
      early spinal cord injury: lack of efficacy to prevent bone loss.
AB  - STUDY DESIGN: Controlled, repeat-measures study. OBJECTIVES: To determine if
      functional electrical stimulation (FES) can affect bone atrophy in early spinal
      cord injury (SCI), and the safety, tolerance and feasibility of this modality in
      bone loss remediation. SETTING: Spinal Injuries Units, Royal Adelaide Hospital
      and Hampstead Rehabilitation Centre, South Australia. METHODS: Patients with
      acute SCI (ASIA A-D) were allocated to FES (n=23, 28+/-9 years, C4-T10, 13 Tetra)
      and control groups (CON, n=10, 31+/-11 years, C5-T12, four Tetra). The
      intervention group received discontinuous FES to lower limb muscles (15 min
      sessions to each leg twice daily, over a 5-day week, for 5 months). Dual energy X
      ray absorptiometry (DEXA) measured total body bone mineral density (tbBMD), hip,
      spine BMD and fat mass (FM) within 3 weeks, and 3 and 6 months postinjury.
      RESULTS: FES and CON groups' tbBMD differed significantly at 3 months postinjury
      (P<0.01), but not thereafter. Other DEXA measures (hip, spine BMD, FM) did not
      differ between groups at any time. No adverse events were identified. CONCLUSION:
      Electrically stimulated muscle activation was elicited, and tetanic effects were
      reproducible; however, there were no convincing trends to suggest that FES can
      play a clinically relevant role in osteoporosis prevention (or subsequent
      fracture risk) in the recently injured patient. The lack of an osteogenic
      response in paralysed extremities to electrically evoked exercise during subacute
      and rehabilitation/recovery phases cannot be fully explained, and may warrant
      further evaluation.

PMID- 16636687
TI  - Spasticity-assessment: a review.
AB  - STUDY DESIGN: Review of the literature on the validity and reliability of
      assessment of spasticity and spasms. OBJECTIVES: Evaluate the most frequently
      used methods for assessment of spasticity and spasms, with particular focus on
      individuals with spinal cord lesions. SETTING: Clinic for Spinal Cord Injuries,
      Rigshospitalet, University Hospital of Copenhagen, and Department of Medical
      Physiology, University of Copenhagen, Denmark. METHODS: The assessment methods
      are grouped into clinical, biomechanical and electrophysiological, and the
      correlation between these is evaluated. RESULTS: Clinical methods: For assessment
      of spasticity, the Ashworth and the modified Ashworth scales are commonly used.
      They provide a semiquantitative measure of the resistance to passive movement,
      but have limited interrater reliability. Guidelines for the testing procedures
      should be adhered to. Spasm frequency scales seem not to have been tested for
      reliability. Biomechanical methods such as isokinetic dynamometers are of value
      when an objective quantitative measure of the resistance to passive movement is
      necessary. They play a minor role in the daily clinical evaluation of spasticity.
      Electrophysiological methods: These techniques have provided valuable insight to
      the pathophysiological mechanisms involved in spasticity, but none of these
      techniques provide an easy and reliable assessment of spasticity for use in the
      daily clinic. CONCLUSION: A combination of electrophysiological and biomechanical
      techniques shows some promise for a full characterization of the spastic
      syndrome. There is a need of simple instruments, which provide a reliable
      quantitative measure with a low interrater variability.

PMID- 16636689
TI  - From species differences to individual differences.

PMID- 16636690
TI  - Assisted reproduction and genetics.

PMID- 16636691
TI  - The need for interaction between assisted reproduction technology and genetics.
      Recommendations of the European Societies of Human Genetics and Human
      Reproduction and Embryology.

PMID- 16636693
TI  - The interface between assisted reproductive technologies and genetics: technical,
      social, ethical and legal issues.
AB  - The interface between assisted reproductive technologies (ART) and genetics
      comprises several sensitive and important issues that affect infertile couples,
      families with severe genetic diseases, potential children, professionals in ART
      and genetics, health care, researchers and the society in general. Genetic causes
      have a considerable involvement in infertility. Genetic conditions may also be
      transmitted to the offspring and hence create transgenerational infertility or
      other serious health problems. Several studies also suggest a slightly elevated
      risk of birth defects in children born following ART. Preimplantation genetic
      diagnosis (PGD) has become widely practiced throughout the world for various
      medical indications, but its limits are being debated. The attitudes towards ART
      and PGD vary substantially within Europe. The purpose of the present paper was to
      outline a framework for development of guidelines to be issued jointly by
      European Society of Human Genetics and European Society of Human Reproduction and
      Embryology for the interface between genetics and ART. Technical, social, ethical
      and legal issues of ART and genetics will be reviewed.

PMID- 16636694
TI  - Hemodynamic disturbances associated with endovascular embolization.

PMID- 16636695
TI  - Zero-filled values enhanced the performance of CRP vs RBP: TTR index in ELBW
      infants.

PMID- 16636697
TI  - Bayesian estimation of the timing and severity of a population bottleneck from
      ancient DNA.
AB  - In this first application of the approximate Bayesian computation approach using
      the serial coalescent, we demonstrated the estimation of historical demographic
      parameters from ancient DNA. We estimated the timing and severity of a population
      bottleneck in an endemic subterranean rodent, Ctenomys sociabilis, over the last
      10,000 y from two cave sites in northern Patagonia, Argentina. Understanding
      population bottlenecks is important in both conservation and evolutionary
      biology. Conservation implications include the maintenance of genetic variation,
      inbreeding, fixation of mildly deleterious alleles, and loss of adaptive
      potential. Evolutionary processes are impacted because of the influence of small
      populations in founder effects and speciation. We found a decrease from a female
      effective population size of 95,231 to less than 300 females at 2,890 y before
      present: a 99.7% decline. Our study demonstrates the persistence of a species
      depauperate in genetic diversity for at least 2,000 y and has implications for
      modes of speciation in the incredibly diverse rodent genus Ctenomys. Our approach
      shows promise for determining demographic parameters for other species with
      ancient and historic samples and demonstrates the power of such an approach using
      ancient DNA.

PMID- 16636698
TI  - Zirconium-mediated metathesis of imines: a study of the scope, longevity, and
      mechanism of a complicated catalytic system.
AB  - By kinetically stabilizing imidozirconocene complexes through the use of a
      sterically demanding ligand, or by generating a more thermodynamically stable
      resting state with addition of diphenylacetylene, we have developed transition
      metal-catalyzed imine metathesis reactions that are mechanistically analogous to
      olefin metathesis reactions catalyzed by metal carbene complexes. When 5 mol % of
      Cp*Cp(THF)Zr=N(t)Bu is used as the catalyst precursor in the metathesis reaction
      between PhCH=NPh and p-TolCH=N-p-Tol, a 1:1:1:1 equilibrium mixture with the two
      mixed imines p-TolCH=NPh and PhCH=N-p-Tol is generated in C(6)D(6) at 105 degrees
      C. The catalyst was still active after 20 days with an estimated 847 turnovers
      (t(1/2) 170 m; TON = 1.77 h(-1)). When the azametallacyclobutene
      Cp(2)Zr(N(Tol)C(Ph)=C(Ph)) is used as the catalyst precursor under similar
      reaction conditions, a total of 410 turnovers are obtained after 4 days (t(1/2)
      170 m; TON = 4.3 h(-1)). An extensive kinetic and equilibrium analysis of the
      metallacyclobutene-catalyzed metathesis of PhCH=N-p-Tol and p-F-C(6)H(4)CH=N-p-F
      C(6)H(4) was carried out by monitoring the concentrations of imines and
      observable metal-containing intermediates over time. Numerical integration
      methods were used to fit these data to a detailed mechanism involving
      coordinatively unsaturated (16-electron) imido complexes as critical
      intermediates. Examination of the scope of reaction between different organic
      imines revealed characteristic selectivity that appears to be unique to the
      zirconium-mediated system. Several zirconocene complexes that could generate the
      catalytically active "CpCp'Zr=NAr" (Cp' = Cp or Cp*) species in situ were found
      to be effective agents in the metathetical exchange between different N-aryl
      imines. N-Alkyl aldimines were found to be completely unreactive toward
      metathesis with N-aryl aldimines, and metathesis reactions involving the two N
      alkyl imines TolCH=NPr and PhCH=NMe gave slow or erratic results, depending on
      the catalyst used. Metathesis was observed between N-aryl ketimines and N-aryl
      aldimines, but for N-aryl ketimine substrates, the catalyst resting state
      consists of zirconocene enamido complexes, generated by the formal C-H activation
      of the alpha position of the ketimine substrates.

PMID- 16636699
TI  - Reactivity of a parent amidoruthenium complex: a transition metal amide of
      exceptionally high basicity.

PMID- 16636700
TI  - High-throughput pharmacokinetic method: cassette dosing in mice associated with
      minuscule serial bleedings and LC/MS/MS analysis.
AB  - A method for pharmacokinetic studies using cassette dosing associated with serial
      bleeding in mice is described. PK profiles of four soluble epoxide hydrolase
      inhibitors were determined following oral, subcutaneous or intraperitoneal
      administration individually or in cassette dosing. Parent analyses were performed
      on only 5 microL of whole blood from serial bleeds (up to 10 per animal), by
      LC/MS/MS. An accuracy (88-100%) and precision (<10% RSD) were observed, leading
      to reliable datum points for PK calculation. PK profiles, T(max), C(max) and half
      life values after cassette dosing were similar to the individual PK results. This
      method dramatically increases speed of data collection while dramatically
      reducing cost and animal usage. The results presented here clearly indicate that
      this proposed method could be applicable to high-throughput PK studies.

PMID- 16636702
TI  - The Medical Library Association Benchmarking Network: development and
      implementation.
AB  - OBJECTIVE: This article explores the development and implementation of the
      Medical Library Association (MLA) Benchmarking Network from the initial idea and
      test survey, to the implementation of a national survey in 2002, to the
      establishment of a continuing program in 2004. Started as a program for hospital
      libraries, it has expanded to include other nonacademic health sciences
      libraries. METHODS: The activities and timelines of MLA's Benchmarking Network
      task forces and editorial board from 1998 to 2004 are described. RESULTS: The
      Benchmarking Network task forces successfully developed an extensive
      questionnaire with parameters of size and measures of library activity and
      published a report of the data collected by September 2002. The data were
      available to all MLA members in the form of aggregate tables. Utilization of Web
      based technologies proved feasible for data intake and interactive display. A
      companion article analyzes and presents some of the data. MLA has continued to
      develop the Benchmarking Network with the completion of a second survey in 2004.
      CONCLUSIONS: The Benchmarking Network has provided many small libraries with
      comparative data to present to their administrators. It is a challenge for the
      future to convince all MLA members to participate in this valuable program.

PMID- 16636703
TI  - The Medical Library Association Benchmarking Network: results.
AB  - OBJECTIVE: This article presents some limited results from the Medical Library
      Association (MLA) Benchmarking Network survey conducted in 2002. Other uses of
      the data are also presented. METHODS: After several years of development and
      testing, a Web-based survey opened for data input in December 2001. Three hundred
      eighty-five MLA members entered data on the size of their institutions and the
      activities of their libraries. The data from 344 hospital libraries were edited
      and selected for reporting in aggregate tables and on an interactive site in the
      Members-Only area of MLANET. The data represent a 16% to 23% return rate and have
      a 95% confidence level. RESULTS: Specific questions can be answered using the
      reports. The data can be used to review internal processes, perform outcomes
      benchmarking, retest a hypothesis, refute a previous survey findings, or develop
      library standards. The data can be used to compare to current surveys or look for
      trends by comparing the data to past surveys. CONCLUSIONS: The impact of this
      project on MLA will reach into areas of research and advocacy. The data will be
      useful in the everyday working of small health sciences libraries as well as
      provide concrete data on the current practices of health sciences libraries.

PMID- 16636704
TI  - How to identify randomized controlled trials in MEDLINE: ten years on.
AB  - OBJECTIVE: The researchers sought to assess whether the widely used 1994 Cochrane
      Highly Sensitive Search Strategy (HSSS) for randomized controlled trials (RCTs)
      in MEDLINE could be improved in terms of sensitivity, precision, or parsimony.
      METHODS: A gold standard of 1,347 RCT records and a comparison group of 2,400 non
      trials were randomly selected from MEDLINE. Terms occurring in at least 1% of RCT
      records were identified. Fifty percent of the RCT and comparison group records
      were randomly selected, and the ability of the terms to discriminate RCTs from
      non-trial records was determined using logistic regression. The best performing
      combinations of terms were tested on the remaining records and in MEDLINE.
      RESULTS: The best discriminating term was "Clinical Trial" (Publication Type). In
      years where the Cochrane assessment of MEDLINE records had taken place, the
      strategies identified few additional unindexed records of trials. In years where
      Cochrane assessment has yet to take place, "Randomized Controlled Trial"
      (Publication Type) proved highly sensitive and precise. Adding six more search
      terms identified further, unindexed trials at reasonable levels of precision and
      with sensitivity almost equal to the Cochrane HSSS. CONCLUSIONS: Most reports of
      RCTs in MEDLINE can now be identified easily using "Randomized Controlled Trial"
      (Publication Type). More sensitive searches can be achieved by a brief strategy,
      the Centre for Reviews and Dissemination/Cochrane Highly Sensitive Search
      Strategy (2005 revision).

PMID- 16636705
TI  - Physician use of the curbside consultation to address information needs: report
      on a collective case study.
AB  - PURPOSE: The author reports key findings from a doctoral dissertation
      investigating what the curbside consultation is, how and why physicians use it,
      and what the implications for health sciences library services might be.
      SETTINGS/INFORMANTS: Primary informants included sixteen primary care physicians
      at six sites in one Midwestern state. Additional informants included twenty-eight
      specialists and subspecialists identified by the primary informants as colleagues
      who provided curbside consultations. METHODS: Qualitative research methods were
      used, including field observations, formal and informal interviews, and
      conversations with peer review physicians. RESULTS: Despite a lack of consensus
      about what constitutes a "good" curbside consultation, physician informants
      reported that curbside consultations were part of their medical education and
      that they continued to take part in them for a number of reasons. Tacit rules
      govern curbside consultation interactions, and negative consequences result when
      the rules are misunderstood or not observed. DISCUSSION/CONCLUSION: Acknowledging
      and understanding physicians' use of the curbside consultation to obtain and
      construct knowledge may suggest new ways for health sciences librarians to work
      with physicians in locating, diffusing, and disseminating clinical information.

PMID- 16636707
TI  - Consumer health information for pet owners.
AB  - OBJECTIVE: The author studied health information available for veterinary
      consumers both in print and online. METHODS: WorldCat was searched using a list
      of fifty-three Library of Congress subject headings relevant to veterinary
      consumer health to identify print resources for review. Identified items were
      then collected and assessed for authority, comprehensiveness of coverage,
      validity, and other criteria outlined by Rees. An in-depth assessment of the
      information available for feline lower urinary tract disease (FLUTD) and canine
      congestive heart failure (CHF) was then conducted to examine the availability and
      quality of information available for specific diseases and disorders. A reading
      grade level was assigned for each passage using the Flesch-Kincaid formula in the
      Readability Statistics feature in Microsoft Word. RESULTS/DISCUSSION: A total of
      187 books and 7 Websites were identified and evaluated. More than half of the
      passages relating to FLUTD and CHF were written above an 11th-grade reading
      level. A limited quantity of quality, in-depth resources that address specific
      diseases and disorders and are written at an appropriate reading level for
      consumers is available. CONCLUSION: The library's role is to facilitate access to
      the limited number of quality consumer health resources that are available to
      veterinary consumers.

PMID- 16636706
TI  - The information seeking of on-duty critical care nurses: evidence from
      participant observation and in-context interviews.
AB  - OBJECTIVES: An observational study describes on-duty nurses' informative
      behaviors from the perspective of library and information science, rather than
      patient care,. It reveals their information sources, the kinds of information
      they seek, and their barriers to information acquisition. METHODS: Participant
      observation and in-context interviews were used to record in detail fifty hours
      of the information behavior of a purposive sample of on-duty critical care nurses
      on twenty-bed critical care unit in a community hospital. The investigator used
      rigorous ethnographic methods-including open, in vivo, and axial coding--to
      analyze the resulting rich textual data. RESULTS: The nurses' information
      behavior centered on the patient, seeking information from people, the patient
      record, and other systems. The nurses mostly used patient-specific information,
      but they also used some social and logistic information. They occasionally sought
      knowledge-based information. Barriers to information acquisition included
      illegible handwriting, difficult navigation of online systems, equipment failure,
      unavailable people, social protocols, and mistakes caused by people multitasking
      while working with multiple complex systems. Although the participating nurses
      understood and respected evidence-based practice, many believed that taking time
      to read published information on duty was not only difficult, but perhaps also
      ethically wrong. They said that a personal information service available to them
      at all hours of the day or night would be very useful. CONCLUSIONS: On-duty
      critical care nursing is a patient-centric information activity. A major
      implication of this study for librarians is that immediate professional reference
      service--including quality and quantity filtering-may be more useful to on-duty
      nurses than do-it-yourself searching and traditional document delivery are.

PMID- 16636708
TI  - An evaluation of a collaborative model for preparing evidence-based medicine
      teachers.
AB  - PURPOSE: The authors studied the effectiveness of a train-the-trainer
      collaboration model between librarians and medical faculty to instruct librarians
      and health professionals in teaching evidence-based medicine (EBM) principles.
      METHODS: A telephone survey was administered to graduates of an EBM course who
      agreed to participate in the study. They were asked if and how they taught EBM on
      returning to their institutions, if they felt competent to critically appraise an
      article, if their skill in searching PubMed improved, and if they collaborated
      with others in teaching EBM. RESULTS: Most respondents were librarians. The class
      was successful in that most taught EBM on return to their home institutions. Most
      initiated collaboration with health professionals. The goals of improving PubMed
      searching and achieving statistical competency had less success. CONCLUSION: This
      model is effective in preparing librarians to teach EBM. Modeling and encouraging
      collaboration between librarians and health professionals were successful
      techniques. Librarians would like more instruction in statistical concepts and
      less in searching PubMed. conclusions cannot be made for health professionals
      because of the low response rate from this group. As evidence-based health care
      continues to extend to other disciplines, librarians can position themselves to
      participate fully in the EBM educational process.

PMID- 16636709
TI  - "Mini-Medical School for Librarians": from needs assessment to educational
      outcomes.
AB  - PURPOSE: This study evaluates the outcomes of the "Mini-Medical School for
      Librarians" or "Medical School Experience," a continuing education symposium
      designed to improve librarians' understanding of medicine and medical education.
      SUBJECTS: The subjects are the symposium participants, a group that consisted of
      fifty-eight medical librarians and other information professionals. METHODOLOGY:
      Pre- and post-symposium self-evaluation surveys gauged participants' self
      assessed confidence with the course content. A follow-up survey was administered
      six months after the symposium. A learning action plan recorded both the intended
      and actual applications of course content to professional settings. RESULTS: T
      test analysis of paired pre- and post-symposium responses reveal a significant
      positive change in the mean self-assessed confidence with course content
      immediately following the symposium. Pairings of post-symposium and follow-up
      survey responses indicate a slight reversal in attendees' confidence in the
      months following the symposium, but pairings of pre-symposium and follow-up
      survey results demonstrate that the longitudinal impact of the program on self
      assessed confidence with course content was positive and significant. Analysis of
      the learning action plan revealed a disparity in how participants planned to use
      the information they learned in the course and how they actually used it.
      CONCLUSIONS: Continuing education programs that address the content and structure
      of medicine can be an effective means by which to inform both the novice's and
      mid-career medical librarian's understanding of medicine and medical education.

PMID- 16636710
TI  - Utilization of the medical librarian in a state Medicaid program to provide
      information services geared to health policy and health disparities.
AB  - OBJECTIVE: The role of two solo medical librarians in supporting Medicaid
      programs by functioning as information specialists at regional and state levels
      is examined. SETTING: A solo librarian for the Massachusetts Medicaid
      (MassHealth) program and a solo librarian for the New England States Consortium
      Systems Organization (NESCSO) functioned as information specialists in context to
      support Medicaid policy development and clinical, administrative, and program
      staff for state Medicaid programs. BRIEF DESCRIPTION: The librarian for
      MassHealth initially focused on acquiring library materials and providing
      research support on culturally competent health care and outreach, as part of the
      United States Department of Health and Human Services Culturally and
      Linguistically Appropriate Services in Health Care Standards. The NESCSO
      librarian focused on state Medicaid system issues surrounding the implementation
      of the Health Insurance Portability and Accountability Act. The research focus
      expanded for both the librarians, shaping their roles to more directly support
      clinical and administrative policy development. Of note, the availability and
      dissemination of information to policy leaders facilitated efforts to reduce
      health disparities. In Massachusetts, this led to a state legislative special
      commission to eliminate health disparities, which released a report in November
      2005. On a regional level, the NESCSO librarian provided opportunities for states
      in New England to share ideas and Medicaid program information. The Centers for
      Medicaid and Medicare are working with NESCSO to explore the potential for using
      the NESCSO model for collaboration for other regions of the United States.
      RESULTS/OUTCOMES: With the increased attention on evidence-based health care and
      reduction of health disparities, medical librarians are called on to support a
      variety of health care information needs. Nationally, state Medicaid programs are
      being called on to provide coverage and make complex medical decisions regarding
      the delivery of benefits. Increasing numbers of beneficiaries and shrinking
      Medicaid budgets demand effective and proactive decision making to provide
      quality care and to accomplish the missions of state Medicaid programs. In this
      environment, the opportunities for information professionals to provide value and
      knowledge management are increasing.

PMID- 16636711
TI  - Health information Hispanic outreach in the Texas Lower Rio Grande Valley.
AB  - PURPOSE: This paper provides an overview of the two-year Texas Lower Rio Grande
      Valley Health Information Hispanic Outreach (HI HO) project. The project included
      a needs assessment, four pilot projects, and focus groups on the use of
      MedlinePlus and MedlinePlus en espanol. The needs assessment included a survey of
      physicians' information usage and a review of the circuit librarian program that
      had been established in 1989. The pilot projects were located at a high school, a
      rural health clinic, an urban health clinic, and a community center. Diffusion of
      innovation theory provided a framework for interpreting the results of the pilot
      projects. METHODS: The survey of physicians' information usage partially
      replicated a similar 1990 survey. The review of the circuit librarian program
      included usage statistics, interviews of administrators, and a survey of
      participants. Pilot project methodology varied by site. At the high school, four
      students were trained to instruct their peers in the use of MedlinePlus. At the
      two clinics, a computer workstation was installed for patients to access
      MedlinePlus. At the community center, staff were trained to use MedlinePlus en
      espanol to train community residents. Project evaluation included surveys, focus
      groups, and interviews. Indicators of success included increased level of
      consumer use of MedlinePlus, reports by key informants and consumers of how
      MedlinePlus was used, reports about training, and development of self-sustaining
      activity. RESULTS: The physician survey documented usage of health information
      resources in 2002 compared to 1990. The review of the circuit librarian program
      documented the change in program usage between 1989 and 2003. The pilot project
      at the high school was the most successful of the four pilot projects in
      introducing MedlinePlus to a large number of people, followed by the community
      center project. In the high school and community center projects, the
      participating institutions had reinforcing educational missions and paid staff
      who were highly motivated to achieve the project goals. The computer workstations
      projects at the two clinics were less successful, due in part to limited staff
      commitment and conflicting priorities. CONCLUSIONS: The HI HO project tested
      methods of reaching the Hispanic community in the Lower Rio Grande Valley region
      of Texas. The four HI HO pilot projects varied in achieving their stated
      objectives. But taken as a whole, the HI HO project significantly contributed to
      a better understanding of health information outreach to the Hispanic community,
      knowledge that should be useful to others with similar outreach activities.

PMID- 16636712
TI  - Clinical Digital Libraries Project: design approach and exploratory assessment of
      timely use in clinical environments.
AB  - OBJECTIVE: The paper describes and evaluates the use of Clinical Digital
      Libraries Project (CDLP) digital library collections in terms of their
      facilitation of timely clinical information seeking. DESIGN: A convenience sample
      of CDLP Web server log activity over a twelve-month period (7/2002 to 6/2003) was
      analyzed for evidence of timely information seeking after users were referred to
      digital library clinical topic pages from Web search engines. Sample searches
      were limited to those originating from medical schools (26% North American and
      19% non-North American) and from hospitals or clinics (51% North American and 4%
      non-North American). MEASUREMENT: Timeliness was determined based on a
      calculation of the difference between the timestamps of the first and last Web
      server log "hit" during each search in the sample. The calculated differences
      were mapped into one of three ranges: less than one minute, one to three minutes,
      and three to five minutes. RESULTS: Of the 864 searches analyzed, 48% were less
      than 1 minute, 41% were 1 to 3 minutes, and 11% were 3 to 5 minutes. These
      results were further analyzed by environment (medical schools versus hospitals or
      clinics) and by geographic location (North America versus non-North American).
      Searches reflected a consistent pattern of less than 1 minute in these
      environments. Though the results were not consistent on a month-by-month basis
      over the entire time period, data for 8 of 12 months showed that searches shorter
      than 1 minute predominated and data for 1 month showed an equal number of less
      than 1 minute and 1 to 3 minute searches. CONCLUSIONS: The CDLP digital library
      collections provided timely access to high-quality Web clinical resources when
      used for information seeking in medical education and hospital or clinic
      environments from North American and non-North American locations and
      consistently provided access to the sought information within the documented two
      minute standard. The limitations of the use of Web server data warrant an
      exploratory assessment. This research also suggests the need for further
      investigation in the area of timely digital library collection services to
      clinical environments.

PMID- 16636713
TI  - An introduction to the Semantic Web for health sciences librarians.
AB  - OBJECTIVES: The paper (1) introduces health sciences librarians to the main
      concepts and principles of the Semantic Web (SW) and (2) briefly reviews a number
      of projects on the handling of biomedical information that uses SW technology.
      METHODOLOGY: The paper is structured into two main parts. "Semantic Web
      Technology" provides a high-level description, with examples, of the main
      standards and concepts: extensible markup language (XML), Resource Description
      Framework (RDF), RDF Schema (RDFS), ontologies, and their utility in information
      retrieval, concluding with mention of more advanced SW languages and their
      characteristics. "Semantic Web Applications and Research Projects in the
      Biomedical Field" is a brief review of the Unified Medical Language System
      (UMLS), Generalised Architecture for Languages, Encyclopedias and Nomenclatures
      in Medicine (GALEN), HealthCyberMap, LinkBase, and the thesaurus of the National
      Cancer Institute (NCI). The paper also mentions other benefits and by-products of
      the SW, citing projects related to them. DISCUSSION AND CONCLUSIONS: Some of the
      problems facing the SW vision are presented, especially the ways in which the
      librarians' expertise in organizing knowledge and in structuring information may
      contribute to SW projects.

PMID- 16636714
TI  - Mapping the literature of nursing: 1996-2000.
AB  - INTRODUCTION: This project is a collaborative effort of the Task Force on Mapping
      the Nursing Literature of the Nursing and Allied Health Resources Section of the
      Medical Library Association. This overview summarizes eighteen studies covering
      general nursing and sixteen specialties. METHOD: Following a common protocol,
      citations from source journals were analyzed for a three-year period within the
      years 1996 to 2000. Analysis included cited formats, age, and ranking of the
      frequency of cited journal titles. Highly cited journals were analyzed for
      coverage in twelve health sciences and academic databases. RESULTS: Journals were
      the most frequently cited format, followed by books. More than 60% of the cited
      resources were published in the previous seven years. Bradford's law was
      validated, with a small core of cited journals accounting for a third of the
      citations. Medical and science databases provided the most comprehensive access
      for biomedical titles, while CINAHL and PubMed provided the best access for
      nursing journals. DISCUSSION: Beyond a heavily cited core, nursing journal
      citations are widely dispersed among a variety of sources and disciplines, with
      corresponding access via a variety of bibliographic tools. Results underscore the
      interdisciplinary nature of the nursing profession. CONCLUSION: For comprehensive
      searches, nurses need to search multiple databases. Libraries need to provide
      access to databases beyond PubMed, including CINAHL and academic databases.
      Database vendors should improve their coverage of nursing, biomedical, and
      psychosocial titles identified in these studies. Additional research is needed to
      update these studies and analyze nursing specialties not covered.

PMID- 16636715
TI  - Comparison of Medical Subject Headings and standard terminology regarding
      performance of diagnostic tests.

PMID- 16636716
TI  - Plants from many healing landscapes: gathering information and teaching
      clinicians about the cultural use of medicinal herbs.

PMID- 16636717
TI  - Enhancement in dissolution pattern of piribedil by molecular encapsulation with
      beta-cyclodextrin.
AB  - The aim of this study was to improve the dissolution behavior of piribedil by
      molecular encapsulation with beta-cyclodextrin (beta-CD). Toward this aim,
      physical mixing, co-grinding, and spray-drying methods were used to prepare solid
      binary systems. Differential scanning calorimetry, X-ray diffractometry, and
      particle size analysis were used to characterize the binary systems obtained.
      Complexes of piribedil and beta-CD could be prepared using the spray-drying
      method. Dissolution of piribedil was improved to a great extent by the complex
      prepared.

PMID- 16636718
TI  - Effects of artemisinin, artemether, and arteether on the pharmacokinetics of
      phenytoin.
AB  - The aim of the study was to determine the effect of artemisinin, artemether, and
      arteether on the pharmacokinetics of phenytoin in rabbits. In a cross-over study,
      phenytoin (30 mg/kg/day, o.s.) was given daily for 7 days. On day 7, blood
      samples were taken at various time intervals between 0 and 24 h. In the
      artemisinin group, phenytoin was administered for 7 days. On day 8, artemisinin
      alone (82 mg/kg) was administered, followed by artemisinin (41 mg/kg) along with
      phenytoin (30 mg/kg/day) for the next 2 days, and blood samples were drawn at
      various time intervals. For the artemether group, artemether (10 mg/kg, i.m.) was
      given on day 8, followed by artemether (5 mg/kg, i.m.) for 2 days. For the
      arteether group, arteether (10 mg/kg, i.m.) was given from day 8 for 3 days.
      Plasma phenytoin levels were assayed by HPLC, and pharmacokinetic parameters were
      calculated. In the artemisinin group, there was a significant decrease in t(1/2)
      a of phenytoin. In the artemether group, t(1/2) el decreased compared to that of
      controls. In the arteether group, no significant change was observed in the
      pharmacokinetic parameters. These results suggest that artemisinin compounds
      alter the pharmacokinetics of phenytoin. Confirmation of these results in human
      studies will warrant changes in phenytoin dose or frequency, when either of these
      antimalarials is coadministered with it.

PMID- 16636719
TI  - L-NAME prevents anxiety-like and depression-like behavior in rats exposed to
      restraint stress.
AB  - Stressful life events contribute to the development of many neuropsychiatric
      disorders including depression and anxiety. Animal studies based on the
      relationship of stress and depression or anxiety are scarce and controversial.
      Moreover, neither the neurobiological basis of anxiety and depression nor the
      mechanisms responsible for neurochemical regulation by stressful stimuli are well
      understood. This study was designed to investigate the possible contribution of
      both acute (2 h) and chronic (2 h X 15 d) restraint stress in the generation of
      anxiety and depression, and also to find out whether nitric oxide (NO) has a
      modulatory role in these behavioral reactions. Elevated plus-maze and forced
      swimming test (FST) were chosen for assessment of anxiety and depression,
      respectively, and N(G)-nitro L-arginine methyl ester (L-NAME, 10 mg/kg), a NO
      synthase (NOS) inhibitor, and L-arginine (50 mg/kg), a NO precursor, were used to
      evaluate the role of nitrergic system in restraint exposed rats. The results
      showed that acute and chronic stress caused depression-like and anxiety-like
      behaviors in rats and the acute inhibition of NOS by L-NAME prevented these acute
      and chronic stress-induced anxiogenesis and depression. These data lead to the
      conclusion that stress and NO seem to be involved in the generation of anxiety
      and depression.

PMID- 16636720
TI  - Topical amiloride ointment accelerates healing of mechanical skin ulcers in
      albino rabbits and patients.
AB  - The present investigation was undertaken to explore the ulcer-healing property of
      1% amiloride ointment on mechanically produced skin ulcers in albino rabbits and
      at donor site of patients requiring split skin graft. Four skin ulcers measuring
      2 X 2 cm(2) (two on either side of the midline) were made 2 cm apart on the pre
      shaved back of each anesthetized rabbit up to the depth of subcutaneous tissue.
      Ulcers on one side of the midline were treated with sterile soft paraffin and
      served as control, whereas those on the other side were treated with amiloride
      ointment. Each ulcer was observed for its size, slough formation, and any sign of
      irritation on alternate days, until healing was complete. Healing of ulcers was
      significantly (p<0.001) accelerated with amiloride ointment in terms of days
      required for complete healing, ulcer size, and area under the size-time curve. In
      each patient, the anterior thigh was used as donor site. Grafts were harvested
      from midline using Watson's modification of Humby's knife. Each site was divided
      into proximal and distal halves and was covered with either soft paraffin tulle
      serving as control or 1% amiloride tulle as test site and then dressed
      conventionally. Healing was evaluated visually on 10th postoperative day. Healing
      was significantly accelerated by amiloride tulle in terms of days required for
      complete healing (p<0.01), better quality of skin regenerated, leading to ease of
      removal of dressing with less of patient's discomfort, and hence more
      acceptability (p<0.01). No irritation or suppression of immunity was noticeable.
      Thus, topical amiloride may prove to be an inexpensive and better ulcer-healing
      agent with no apparent side effect. Inhibition of urokinase-type plasminogen
      activator and modulation of field strengths by amiloride seem to be responsible
      for this effect.

PMID- 16636721
TI  - Formulation and evaluation of once-a-day transdermal gels of diclofenac
      diethylamine.
AB  - The present study was undertaken to prepare and evaluate transdermal gels of
      diclofenac diethylamine (DDEA) containing penetration enhancers such as olesan
      oil and dimethyl sulfoxide (DMSO). Transdermal gels were prepared using different
      polymers such as carbopol-940, polyvinyl alcohol (PVA), hydroxy propyl methyl
      cellulose-K(4) M, hydroxy propyl cellulose-M, and sodium carboxy methyl
      cellulose. The formulated gels were subjected to physicochemical studies, in
      vitro release studies and in vitro skin permeations studies and were evaluated
      for drug content, viscosity, extrudability, spreadability, and pH. The in vitro
      release studies of prepared gels were performed using specially designed Fites
      cell and in vitro skin permeation studies were performed using keshary-chien
      diffusion cell through rat skin. Selected formulations were evaluated for their
      antiinflammatory activity using the carrageenan-induced paw edema in rats. The
      carbopol-940 and PVA gels containing 10% DMSO showed best in vitro skin
      permeation of DDEA. In vivo study for the selected formulation showed a sustained
      reduction in inflammation in the carrageenan induced paw edema in rats. The
      efficacies of carbopol-940 and PVA gels were also compared with that of the
      marketed Voveran gel,(R) and it was found that carbopol and PVA gels produced
      better results than the Voveran gel. (c) 2006 Prous Science. All rights reserved.

PMID- 16636722
TI  - Evaluation of the clinical and histological effectiveness of isotretinoin in the
      therapy of oral leukoplakia: ten years of experience: is management still up to
      date and effective?
AB  - Various studies have evaluated the therapeutic effectiveness of vitamin A
      derivatives in the treatment of oral leukoplakia (OL). Not all the studies have
      shown concordant results. The aim of our study, which has a 10-year follow-up,
      was to test the effectiveness of topical therapy based on 0.18% isotretinoin by
      comparing it with that most frequently used, i.e., at 0.05% concentration. Forty
      patients with an established diagnosis of OL were involved in the study. The
      patients were randomly divided into two groups and the drug was administered
      topically at 0.05% and 0.18% concentrations. The drug was applied twice a day for
      3 consecutive months; then it was suspended for 1 month, and the biopsy sample
      was repeated for the histological follow-up. The higher concentration of the
      drug, according to the same protocol, was administered to patients who did not
      benefit from the lower concentration. The results showed a significant reduction
      in lesions (85%), with no documented topical or systemic adverse reactions at
      0.18% concentration. A significant reduction of the aggressiveness of the disease
      and the disappearance of dysplastic phenomena were observed histologically. The
      proposed therapeutic protocol was effective toward highly active oral leukoplakia
      with dysplastic phenomena, and therefore at higher risk of malignant progression.

PMID- 16636723
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials are a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables have been
      retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the
      drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate,
      abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept,
      alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin,
      axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart,
      bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate,
      canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride,
      cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride,
      cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent,
      CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine,
      Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin
      10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim,
      edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol
      sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol,
      etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib,
      gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol,
      human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza
      vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro,
      irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate,
      lapatinib, letrozole, levocetirizine, lomustine, lonafarnib,
      lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride,
      methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate,
      monophosphoryl lipid A, montelukast sodium, motexafin gadolinium, mycophenolate
      mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX
      015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid
      hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b,
      peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich
      phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide
      acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine,
      rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone,
      rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin
      hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan
      hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil,
      tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide,
      tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib,
      vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome
      influenza vaccine, voriconazole; Zidovudine.

PMID- 16636724
TI  - Sulfur and iron in shipwrecks cause conservation concerns.
AB  - Synchrotron-based sulfur X-ray absorption spectroscopy reveals considerable
      accumulation of organosulfur (e.g. thiols), pyrite and iron(II) sulfides in
      marine-archaeological wood preserved in seawater, e.g. for historical shipwrecks
      such as the Vasa and Mary Rose. In the museum, oxidation of the sulfur compounds
      in the presence of iron ions may cause severe acidity in the moist wood. This
      tutorial review discusses developments of conservation methods to remove acid and
      iron, and how to analyse and stabilise sulfur compounds in the wood.

PMID- 16636725
TI  - Heterovalent selectivity and the combinatorial advantage.
AB  - Libraries of monovalent compounds can be reacted with each other to give
      libraries of bivalent ones. If those reactions are efficient, and if the products
      do not need to be purified, large numbers of bivalent compounds can be produced
      rapidly, and one might say there is a "combinatorial advantage" to doing so.
      However, selective formation of heterobivalent products must be possible
      otherwise statistical mixtures will form. This tutorial review describes methods
      that will give heterobivalent compounds almost exclusively. Although there are
      relatively few methods that will give that desired selectivity, such methods are
      becoming increasingly important as the potential applications of bi- and
      multivalent compounds emerge.

PMID- 16636726
TI  - Current trends and future challenges in the experimental, theoretical and
      computational analysis of intervalence charge transfer (IVCT) transitions.
AB  - Mixed-valence chemistry has a long and rich history which is characterised by a
      strong interplay of experimental, theoretical and computational studies. The
      intervalence charge transfer (IVCT) transitions generated in dinuclear mixed
      valence species (particularly of ruthenium and osmium) have received considerable
      attention in this context, as they provide a powerful and sensitive probe of the
      factors which govern electronic delocalisation and the activation barrier to
      intramolecular electron transfer. This tutorial review discusses classical, semi
      classical and quantum mechanical theoretical treatments which have been developed
      over the past 35 years for the analysis of IVCT absorption bands. Particular
      attention is drawn to the applicability of these models for the analysis of mixed
      valence complexes which lie between the fully localised (Class II) and
      delocalised (Class III) limits in the "localised-to-delocalised" (Class II-III)
      regime. A clear understanding of the complex interplay of inter- and
      intramolecular factors which influence the IVCT process is crucial for the design
      of experimental studies to probe the localised-to-delocalised regime and in
      guidance of the development of appropriate theoretical models.

PMID- 16636727
TI  - Photochemical reactions in the tropospheric aqueous phase and on particulate
      matter.
AB  - This paper is a tutorial review in the field of atmospheric chemistry. It
      describes some recent developments in tropospheric photochemistry in the aqueous
      phase and on particulate matter. The main focus is regarding the transformation
      processes that photochemical reactions induce on organic compounds. The relevant
      reactions can take place both on the surface of dispersed particles and within
      liquid droplets (e.g. cloud, fog, mist, dew). Direct and sensitised photolysis
      and the photogeneration of radical species are the main processes involved.
      Direct photolysis can be very important in the transformation of particle
      adsorbed compounds. The significance of direct photolysis depends on the
      substrate under consideration and on the colour of the particle: dark
      carbonaceous material shields light, therefore protecting the adsorbed molecules
      from photodegradation, while a much lower protection is afforded for the light
      shaded mineral fraction of particulate. Particulate matter is also rich in
      photosensitisers (e.g. quinones and aromatic carbonyls), partially derived from
      PAH photodegradation. These compounds can induce degradation of other molecules
      upon radiation absorption. Interestingly, substrates such as methoxyphenols,
      major constituents of wood-smoke aerosol, can also enhance the degradation of
      some sensitisers. Photosensitised processes in the tropospheric aqueous phase
      have been much less studied: it will be interesting to assess the photochemical
      properties of Humic-Like Substances (HULIS) that are major components of liquid
      droplets. The main photochemical sources of reactive radical species in aqueous
      solution and on particulate matter are hydrogen peroxide, nitrate, nitrite, and
      Fe(iii) compounds and oxides. The photogeneration of hydroxyl radicals can be
      important in polluted areas, while their transfer from the gas phase and dark
      generation are usually prevailing on an average continental scale. The reactions
      involving hydroxyl radicals can induce very fast transformation of compounds
      reacting with (*)OH at a diffusion-controlled rate (10(10) M(-1) s(-1)), with
      time scales of an hour or less. The hydroxyl-induced reactivity in solution can
      be faster than in the gas phase, influencing the degradation kinetics of water
      soluble compounds. Moreover, photochemical processes in fog and cloudwater can be
      important sources of secondary pollutants such as nitro-, nitroso-, and chloro
      derivatives.

PMID- 16636728
TI  - Catalytic asymmetric approaches towards enantiomerically enriched diarylmethanols
      and diarylmethylamines.
AB  - Enantiopure diarylmethanols and diarylmethylamines are important intermediates
      for the synthesis of pharmaceutically relevant products with antihistaminic,
      antiarrhythmic, diuretic, antidepressive, laxative, local-anesthetic and
      anticholinergic properties. Furthermore, they have been used as precursors for
      1,1-diarylalkyl moieties, which occur in other antidepressants as well as in
      antimuscarinics and endothelin antagonists. In this critical review catalytic
      strategies towards enantioenriched diarylmethanols and diarylmethylamines are
      discussed, including methods for asymmetric carbon-carbon bond formations by aryl
      transfer reactions to aldehydes and arylimines, respectively, and
      enantioselective reductions of diarylketones.

PMID- 16636729
TI  - Multifunctional molecular carbon materials--from fullerenes to carbon nanotubes.
AB  - This critical review covers the timely topic of carbon nanostructures-fullerenes
      and carbon nanotubes-in combination with metalloporphyrins as integrative
      components for electron-donor-acceptor ensembles. These ensembles are typically
      probed in condensed media and at semi-transparent electrode surfaces. In
      particular, we will present a comprehensive survey of a variety of covalent
      (i.e., nanoconjugates) and non-covalent linkages (i.e., nanohybrids) to
      demonstrate how to govern/fine-tune the electronic interactions in the resulting
      electron-donor-acceptor ensembles. In the context of covalent bridges, different
      spacers will be discussed, which range from pure "insulators" (i.e., amide bonds,
      etc.) to sophisticated "molecular wires" (i.e., p-phenylenevinylene units, etc.).
      Furthermore, we will elucidate the fundamental impact that these vastly different
      spacers may exert on the rate, efficiency, and mechanism of short- and long-range
      electron transfer reactions. Additionally, a series of non-covalent motifs will
      be described: hydrogen bonding, complementary electrostatics, pi-pi stacking and
      metal coordination-to name a few. These motifs have been successfully employed by
      us and our collaborators en route towards novel architectures (i.e., linear
      structures, tubular structures, rotaxanes, catenanes, etc.) that exhibit unique
      and remarkable charge transfer features.

PMID- 16636730
TI  - Perinatal health in Rio de Janeiro.

PMID- 16636731
TI  - [Perinatal mortality research in Brazil: review of methodology and results].
AB  - The perinatal mortality rate remains a public health problem, demanding
      epidemiological studies to describe its magnitude and time trends, identify risk
      factors, and define adequate interventions. There are still methodological
      controversies, resulting in heterogeneous studies and possible biases. In Brazil,
      there has been a growing scientific output on this theme, mainly in the South and
      Southeast of the country. Twenty-four articles from 1996 to 2003 were reviewed,
      focusing on definitions and classifications, data sources, study designs,
      measurement of variables, statistical analysis, and results. The review showed an
      increasing utilization of data bases (mainly SINASC and SIM), few studies on
      stillbirth, the incorporation of classification schemes, and disagreement
      concerning risk factors.

PMID- 16636732
TI  - [Factors associated with perinatal morbidity and mortality in a sample of public
      and private maternity centers in the City of Rio de Janeiro, 1999-2001].
AB  - This study compares socio-demographic factors, mothers' biological
      characteristics, and quality of care at maternity hospitals in the City of Rio de
      Janeiro, Brazil. A sample of 10,072 post-partum women in 47 hospitals was
      selected. Data were collected by interviewing mothers in the immediate post
      partum and from medical records. The chi2 test was used to analyze homogeneity of
      ratios. Significant differences were found between patients in public and private
      hospitals in relation to family support, healthy habits during pregnancy,
      reproductive history, access to and satisfaction with prenatal care and delivery,
      and particularly adverse effects in the newborns. Private maternity hospitals
      showed better results, although they displayed excessive cesarean and neonatal
      inter-hospital transfer rates. The stratum consisting of public Federal and State
      maternity hospitals received women with greater morbidity, had lower neonatal
      transfer rates, and received a more positive assessment by clients of the Unified
      National Health System (SUS). Private maternity centers contracted out by the SUS
      were the ones that most refused treatment to patients, leading to delays in
      patient care for delivery.

PMID- 16636733
TI  - [Consistency between data sources and inter-observer reliability in the Study on
      Neonatal and Perinatal Morbidity and Mortality and Care in the City of Rio de
      Janeiro].
AB  - The objective of this study was to evaluate the quality of data in the research
      project entitled "Study on Neonatal and Perinatal Morbidity and Mortality and
      Care in the City of Rio de Janeiro", analyzing the completeness of patient
      records, inter-observer reliability, and concordance of collected data. The study
      interviewed a sample of 10,072 post-partum women, corresponding to 10.0% of the
      deliveries in the City of Rio de Janeiro. This article analyzed the concordance
      between data on patient records and the reproducibility of questionnaires by mean
      of rest/ retest, using common and prevalence-adjusted Kappa as well as the intra
      class correlation coefficient. Losses totaled 4.5%, and the proportion of unknown
      data on patient records varied from 3.0 to 90.0%. Lower proportions were
      concentrated in the neonatal assessment and higher ones in the data on maternal
      hospital admission. There was a high concordance between the data reported by the
      mother and that written on the patient record, with the Kappa varying from 0.77
      to 0.96. In the test/retest verification, Kappa varied from 0.61 to 0.94. This
      study demonstrated a high inter-observer reliability as well as reliability
      between the different data sources (interviewee and patient record).

PMID- 16636734
TI  - [Socioeconomic inequalities and low birth weight and perinatal mortality in Rio
      de Janeiro, Brazil].
AB  - Socioeconomic inequalities in early infant mortality have been evidenced in
      Brazil, with a greater mortality risk associated with the mother's socioeconomic
      status (SES). The aim of this paper is to identify socioeconomic inequalities in
      relation to low birth weight and perinatal mortality in the City of Rio de
      Janeiro, Brazil, discussing the appropriateness of the main health inequality
      indexes proposed in the international literature. As the information source, we
      use data collected in a survey of approximately 10,000 mothers selected for
      interview within 48 hours after delivery in public and private hospitals in the
      city. Using educational level and head of household's income as indicators of
      SES, as well as population attributable risk and slope index of inequality as
      health inequality measures, the results show a steep socioeconomic gradient in
      the proportion of low birth weight, and especially in the perinatal mortality
      rate. The persistent association between socioeconomic indicators and adverse
      results in pregnancy indicates (at least partially) the health system's
      inefficacy in diminishing perinatal health inequalities in Rio de Janeiro.

PMID- 16636735
TI  - [Aspects of women's satisfaction with childbirth care in a maternity hospital in
      Rio de Janeiro].
AB  - The objective of this study was to evaluate factors associated with women's
      satisfaction with vaginal delivery at the Leila Diniz Maternity Hospital in Rio
      de Janeiro, Brazil. A cross-sectional study was conducted from March 1 to 30,
      1999, using interviews with women who had undergone vaginal delivery. In order to
      analyze women's satisfaction, the following were used: (a) a scale to evaluate
      overall satisfaction with the birthing process; (b) description of the woman's
      reasons for this evaluation; and (c) analysis of factors associated with the
      evaluation of childbirth satisfaction. Chi-square for trend with a 5%
      significance level was used to analyze the results. The results of the study
      showed high satisfaction with childbirth care (67%), determined mainly by short
      labor time, good treatment by staff, low level of distress, absence of
      complications for the mother and baby, and presence of a family companion. The
      study also verified the association between women's satisfaction with information
      received during perinatal care and positive perceptions of the professionals
      responsible for providing care.

PMID- 16636736
TI  - [Use of the modified Kotelchuck index in the evaluation of prenatal care and its
      relationship to maternal characteristics and birth weight in Rio de Janeiro,
      Brazil].
AB  - The Kotelchuck index (KI) was modified and used to evaluate prenatal care
      provided in the City of Rio de Janeiro, Brazil, in a sample of 9,920 post-partum
      women following singleton deliveries. Ordinal logistic regression (OLR) and
      multivariate linear regression (LMR) were used to estimate the importance of
      demographic, psychosocial, and obstetric factors for modified KI and the effects
      on birth weight (BW), respectively. Only 38.5% of the sample was classified as
      having received adequate or intensive prenatal care. After adjusting for other
      predictors, the explanatory variables for KI were: mother's schooling, living
      with the newborn's father, attempted abortion, diabetes mellitus, satisfaction
      with pregnancy, skin color, parity, age, and place of residence. BW was
      associated with the modified KI, even after controlling for socio-demographic,
      behavioral, and biological variables. Adequate utilization of prenatal care in
      the City of Rio de Janeiro contributed to the prevention of low BW, and the
      mothers who used prenatal services less presented worse conditions in terms of
      socioeconomic status, schooling, family support, and obstetric risk.

PMID- 16636737
TI  - [Prescribed and reported drug use during pregnancy].
AB  - Few studies describe drug utilization in pregnancy focusing on prescribing
      practices. This study is part of a larger survey on perinatal care in the City of
      Rio de Janeiro, Brazil. The type of hospital (public, contracted out by the
      Unified National Health System, or private) determined the stratification of
      10,072 hospitalized post-partum women, who were asked about medication used
      during pregnancy. Hospital records supplied information on drugs prescribed
      during labor. Drugs were classified according to the Anatomical Therapeutic
      Chemical (ATC) system. Another system was used for specific cases of referred
      use. A mean of 2.08 drugs was prescribed during labor, and a mean of 2.3 was
      reported during pregnancy. Anesthetics, antibiotics, oxytocin, and analgesics
      were the most frequently prescribed during labor, with significant differences
      between strata. Ferrous sulfate, vitamins, scopolamine, and acetaminophen were
      the main drugs reported during pregnancy. Women who had attempted abortion
      referred use of various kinds of tea (49.7%) and misoprostol (9.2%). The drug
      utilization pattern was consistent with the literature. This study offers
      knowledge on prescribing patterns during labor and self-reported use during
      pregnancy in both the public and private sectors.

PMID- 16636738
TI  - [Reliability of birth certificate data in Rio de Janeiro, Brazil, 1999-2001].
AB  - The objective of this article is to assess coverage and reliability of data from
      the Information System on Live Births in the City of Rio de Janeiro, based on an
      analysis of live birth certificates issued by the various hospitals and compared
      to information from the "Study on Neonatal and Perinatal Morbidity and Mortality
      and Care in the City of Rio de Janeiro". A total of 9,608 interviews with post
      partum women were paired case-by-case with the respective birth certificates. The
      statistical analysis consisted of calculating the Kappa index adjusted to the
      prevalence of categorical variables and the intra-class correlation coefficient
      for continuous variables, with a 95% significance level. The study showed
      excellent coverage (96.5%) for hospital births in the City of Rio de Janeiro
      during the period studied. The variables presenting the highest concordance
      levels (over 0.90) were the infant's sex, birth weight, mother's age, type of
      delivery, and type of pregnancy. The variables marital status, mother's
      schooling, and number of prenatal visits showed lower reliability indices (Kappa
      < 0.70). The article discusses the importance of data quality in the Information
      System on Live Births (SINASC) and the system's use as a tool to help define
      maternal and child health policies.

PMID- 16636739
TI  - [Study of validity in self-reported weight and height among pregnant women
      treated at municipal maternity hospitals in Rio de Janeiro, Brazil].
AB  - The main objectives of this article are the assessment of agreement between
      measure-based and report-based information on weight and height, besides the
      identification of the main characteristics related to 150 pregnant women who
      could report (versus could not report) their pre-gestational weight, weight at
      delivery, and height. According to the results, report-based information on
      previous weight is close to the measure-based information (Pearson coefficient
      correlation 0.96 and intra-class correlation 0.92; p < 0.05), with the same
      occurring for weight at delivery (Pearson coefficient correlation 0.96 and intra
      class correlation 0.95; p < 0.05). Nevertheless, linear regression analysis
      detects that this relationship is troublesome for the height variable (beta0 =
      45.5 and beta1 = 0.71; p < 0.05), and therefore the report-based information for
      height must be used cautiously when the measure-based values are not available.
      In relation to the characterization of the group of pregnant women who did not
      inform the three measures (n = 141), these women have the least schooling
      (63.9%), did not attend or attended fewer prenatal appointments (64.3%), and
      entered the prenatal program later, when they were already in the second or third
      trimester (59.3%).

PMID- 16636740
TI  - [Factors associated with precarious prenatal care in a sample of post-partum
      adolescent mothers in maternity hospitals in Rio de Janeiro, Brazil, 1999-2000].
AB  - This study characterizes the women receiving precarious prenatal care according
      to socio-demographic variables, mother's reproductive history, family support,
      satisfaction with pregnancy, and risk behavior during pregnancy. A total of 1,967
      adolescents were interviewed in the immediate post-partum in public and
      outsourced maternity hospitals in the City of Rio de Janeiro. The dependent
      variable was the number of prenatal appointments (0-3; 4-6; 7 or more). The
      statistical analysis aimed to test the hypothesis of homogeneity of proportions,
      including bi- and multivariate analysis, using multinomial logistic regression,
      in which the reference category for the response variable was 7 or more prenatal
      visits. Higher (and statistically significant) proportions of insufficient number
      of prenatal visits (0-3) were associated with: precarious sanitation conditions;
      not living with the child's father; attempted abortion; and smoking, drinking,
      and/or drug use during pregnancy. The results strongly indicate that mothers with
      worse living conditions and risk behavior during pregnancy were the same who
      lacked access to prenatal care.

PMID- 16636741
TI  - [A socioeconomic and psychosocial profile of post-partum adolescents in the City
      of Rio de Janeiro, Brazil, 1999-2001].
AB  - This study aimed to describe the socioeconomic and psychosocial characteristics
      of a sample of teenage mothers classified according to marital status and age
      group. A sample of 1,228 adolescent mothers was interviewed in the immediate post
      partum, selected from public and private hospitals in the City of Rio de Janeiro,
      Brazil. The chi-square test (chi2) was used to verify the hypothesis of
      homogeneity of proportions. Comparing the groups, we found that single and
      younger adolescents were at increased risk of unwanted pregnancy, less family
      support, and more abortions. Fathers of the infants also tended to be adolescents
      and unemployed. Adherence to prenatal care was influenced by the adolescent's
      marital status. The results showed that the most disadvantaged socioeconomic and
      psychosocial conditions were found among single and younger adolescents.

PMID- 16636742
TI  - [Food consumption by pregnant adolescents in Rio de Janeiro, Brazil].
AB  - The increase in teenage pregnancy has been viewed with concern by public health
      experts. Food consumption to help maintain high nutrient demands has been
      identified as one of the most relevant components. This study aims to present the
      habitual consumption of food and energy-specific nutrients by pregnant
      adolescents. A total of 1,180 adolescent mothers were interviewed in maternity
      hospitals in the City of Rio de Janeiro, and a simplified questionnaire on semi
      quantitative frequency of food consumption was applied. Lower consumption of
      fruit juice, vegetables, and fruits was observed among adolescent mothers over
      15. Adolescent mothers classified in the lowest quartile of consumption lack the
      minimum recommended consumption of energy and nutrients. An inverse association
      was found between the number of household members and energy and nutrient
      consumption. Adolescent mothers who received dietary information and changed
      their eating habits during pregnancy showed better results concerning the
      consumption of energy and nutrients. Prenatal care was a key factor for improving
      the results of pregnancy, emphasizing the importance of providing dietary
      information.

PMID- 16636743
TI  - [Some emotional repercussions of adolescent pregnancy in Rio de Janeiro, Brazil
      (1999-2001)].
AB  - This study analyzed the association between early pregnancy and negative
      emotional repercussions for adolescents, according to socio-demographic and
      psychosocial variables. The study interviewed 1,228 adolescents in maternity
      hospitals in the City of Rio de Janeiro. Emotional repercussions were evaluated
      with negative self-assessment variables, showing little or no expectation towards
      the future, as well as psychological distress. The chi2 test and odds ratio were
      used to analyze the data. Adolescents who reported a negative reaction by the
      family felt less valued (OR 1.8), with little expectation towards the future (OR
      2.3), and presented major psychological distress (OR 1.5). Those not enrolled in
      school when they became pregnant also showed worse self-esteem (OR 1.9) and fewer
      expectations towards the future (OR 2.2). Greater psychological distress was
      inversely related to frequency of prenatal care (0.7). The article concludes that
      family support, regardless of original social conditions, was identified as the
      principal factor for minimizing negative emotional repercussions of pregnancy
      during adolescence.

PMID- 16636745
TI  - An improved technique for isolating codominant compound microsatellite markers.
AB  - An approach for developing codominant polymorphic markers (compound
      microsatellite (SSR) markers), with substantial time and cost savings, is
      introduced in this paper. In this technique, fragments flanked by a compound SSR
      sequence at one end were amplified from the constructed DNA library using
      compound SSR primer (AC)6(AG)5 or (TC)6(AC)5 and an adaptor primer for the
      suppression-PCR. A locus-specific primer was designed from the sequence flanking
      the compound SSR. The primer pairs of the locus-specific and compound SSR primers
      were used as a compound SSR marker. Because only one locus-specific primer was
      needed for design of each marker and only a common compound SSR primer was needed
      as the fluorescence-labeled primer for analyzing all the compound SSR markers,
      this approach substantially reduced the cost of developing codominant markers and
      analyzing their polymorphism. We have demonstrated this technique for Dendropanax
      trifidus and easily developed 11 codominant markers with high polymorphism for D.
      trifidus. Use of the technique for successful isolation of codominant compound
      SSR markers for several other plant species is currently in progress.

PMID- 16636746
TI  - Chromosome evolution in the Laurales based on analyses of original and published
      data.
AB  - We present a summary of currently available chromosome information for all seven
      families in the order Laurales on the basis of original and previously published
      data and discuss the evolution of chromosomes in this order. Based on a total of
      53 genera for which chromosome data were available, basic chromosome numbers
      appear consistent within families: x = 11 (Calycanthaceae); x = 22
      (Atherospermataceae and Siparunaceae); x = 19 (Monimiaceae); and x = 12 and 15
      (Lauraceae). The Hernandiaceae have diverse numbers: x = 15 (Gyrocarpoideae) and
      x = 18 and 20 (Hernandioideae). Karyotype analyses showed that Hennecartia,
      Kibaropsis, and Matthaea (all Monimiaceae) contained two or three sets of four
      distinct chromosomes in 38 somatic chromosomes, suggesting that 2n = 38 was
      derived by aneuploid reduction from 2n = 40, a tetraploid of x = 10. In light of
      the overall framework of phylogenetic relationships in the Laurales, we show that
      x = 11 is an archaic base number in the order and is retained in the
      Calycanthaceae, which are sister to the remainder of the order. Polyploidization
      appears to have occurred from x = 11 to x = 22 in a common clade of the
      Siparunaceae, Atherospermataceae, and Gomortegaceae (although 2n = 42 in the
      Gomortegaceae), and aneuploid reduction from x = 11 to x = 10 occurred in a
      common clade of the Hernandiaceae, Lauraceae, and Monimiaceae. To understand
      chromosome evolution in the Lauraceae, however, more studies are needed of genera
      and species of Cryptocaryeae.

PMID- 16636747
TI  - Japanese macaques form a cross-modal representation of their own species in their
      first year of life.
AB  - We tested whether infant Japanese macaques (Macaca fuscata) have a cross-modal
      representation of their own species. We presented monkeys with a photograph of
      either a monkey or a human face on an LCD monitor after playing back a
      vocalization of one of those two species. The subjects looked at the monitor
      longer when a human face was presented after the monkey vocalization than when
      the same face was presented after human vocalization. This suggests that monkeys
      recall and expect a monkey's face upon hearing a monkey's voice.

PMID- 16636748
TI  - Interstitial docetaxel (taxotere), carmustine and combined interstitial therapy:
      a novel treatment for experimental malignant glioma.
AB  - Docetaxel (Taxotere) is a hemisynthetic, anti-cancer compound with good
      preclinical and clinical activity in a variety of systemic neoplasms. We tested
      its activity against malignant gliomas using local delivery methods. Antitumor
      activity was assessed in vitro against human (U87 and U80 glioma) and rat brain
      tumor (9L gliosarcoma and F98 glioma) cell lines. For in vivo evaluation, we
      incorporated docetaxel into a biodegradable polymer matrix, determined associated
      toxicity in the rat brain, and measured efficacy at extending survival in a rat
      model of malignant glioma. Also, we examined the combined local delivery of
      docetaxel with carmustine (BCNU) against the experimental intracranial glioma.
      Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor
      implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5%
      docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n=15,
      median survival 39.1 days) had significantly improved survival over control
      animals (n=12, median survival 22.5 days, P=0.01). Similarly, animals receiving
      BCNU polymers (n=15, median survival 39.3 days, 13.3% long-term survivors)
      demonstrated an increase in survival compared to the controls (P=0.04). Animals
      receiving the combination polymers demonstrated a modest increase in survival
      compared to either chemotherapeutic agent alone (n=14, median survival 54.9 days,
      28.6% long-term survivors) with markedly improved survival over controls
      (P=0.003). We conclude that locally delivered docetaxel shows promise as a novel
      anti-glioma therapy and that the combination of drug regimens via biodegradable
      polymers may be a great therapeutic benefit to patients with malignant glioma.

PMID- 16636749
TI  - An astroblastoma case associated with loss of heterozygosity on chromosome 9p.
AB  - The tumorigenesis of astroblastomas has not yet been elucidated on the basis of
      histopathological studies, and genetic studies may be useful for obtaining
      additional information regarding the tumorigenesis of these tumors. Here, we
      report an astroblastoma case in which a genetic analysis was performed. A 16-year
      old female with a progressive headache was found to have a demarcated cystic
      tumor with a mural nodule in the right parietal lobe. Total removal of the tumor
      was achieved and a histological examination verified that the tumor was an
      astroblastoma. A genetic analysis using microsatellite markers revealed loss of
      heterozygosity (LOH) on chromosome 9p. The postoperative course was uneventful
      and, to date, she has been followed up for 2 years with no signs of recurrence.
      This is the first reported case of an astroblastoma in which LOH was detected on
      9p. Based on this result, the tumorigenesis of astroblastomas is discussed.

PMID- 16636750
TI  - Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma
      multiforme patients following surgery and irradiation.
AB  - PURPOSE: Because raised matrix metalloprotease (MMP) levels are associated with
      glioma invasion and angiogenesis, we tested the efficacy of marimastat (MT) an
      orally active drug that can reduce MMP levels, in patients with gliomas. PATIENTS
      AND METHODS: A total of 162 patients with intracranial glioblastoma multiforme or
      gliosarcomas who had undergone surgery and radiotherapy participated in this
      multicenter, double-blind, placebo-controlled, parallel group study conducted at
      20 institutions. Seventy-nine patients (57 male, 22 female, median age 58 years)
      were randomized to receive placebo (PB), and 83 patients (51 male, 32 female,
      median age 57 years) were randomized to receive MT, 10 mg orally twice daily,
      until tumor progression. RESULTS: This intention-to-treat efficacy analysis
      showed no statistically significant difference between MT and PB groups with
      respect to survival (P = 0.38, log rank test). The median survival time from
      protocol initiation was 37.9 weeks for the PB group and 42.9 weeks for the MT
      group, with a hazard ratio of 1.16 (95% CI 0.83 to 1.60). There were no
      statistically significant differences in quality of life between the PB and MT
      groups, as assessed by the FACT-BR questionnaire. Musculoskeletal toxicities led
      to dose modification or withdrawal in 20% of MT-treated and 1.2% of PB-treated
      patients. CONCLUSION: MT does not improve survival in patients with glioblastoma
      or gliosarcoma following surgery and radiotherapy. Therefore, single-agent MT
      appears unwarranted; however, MT in combination with cytotoxic chemotherapy may
      be warranted, as suggested by observations in our study and other studies.

PMID- 16636753
TI  - 13C, 15N and 1H resonance assignment of the PDZ1 domain of MAGI-1 using QUASI.

PMID- 16636754
TI  - NMR assignment of region 51-160 of human KIN17, a DNA and RNA-binding protein.

PMID- 16636755
TI  - 1H, 13C, and 15N NMR assignment of the Rep protein nuclease domain from the
      porcine circovirus PCV2.

PMID- 16636770
TI  - Anal sphincter lacerations and upright delivery postures--a risk analysis from a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate obstetric sphincter lacerations after a kneeling or
      sitting position at second stage of labor in a multivariate risk analysis model.
      MATERIALS AND METHODS: Two hundred and seventy-one primiparous women with normal
      pregnancies and spontaneous labor were randomized, 138 to a kneeling position and
      133 to a sitting position. Medical data were retrieved from delivery charts and
      partograms. Risk factors were tested in a multivariate logistic regression model
      in a stepwise manner. RESULTS: The trial was completed by 106 subjects in the
      kneeling group and 112 subjects in the sitting group. There were no significant
      differences with regard to duration of second stage of labor or pre-trial
      maternal characteristics between the two groups. Obstetrical sphincter tears did
      not differ significantly between the two groups but an intact perineum was more
      common in the kneeling group (p<0.03) and episiotomy (mediolateral) was more
      common in the sitting group (p<0.05). Three grade IV sphincter lacerations
      occurred in the sitting group compared to none in the kneeling group (NS).
      Multivariate risk analysis indicated that prolonged duration of second stage of
      labor and episiotomy were associated with an increased risk of third- or fourth
      degree sphincter tears (p<0.01 and p<0.05, respectively). Delivery posture,
      maternal age, fetal weight, use of oxytocin, and use of epidural analgesia did
      not increase the risk of obstetrical anal sphincter lacerations in the two
      upright postures. CONCLUSION: Obstetrical anal sphincter lacerations did not
      differ significantly between a kneeling or sitting upright delivery posture.
      Episiotomy was more common after a sitting delivery posture, which may be
      associated with an increased risk of anal sphincter lacerations. Upright delivery
      postures may be encouraged in healthy women with normal, full-term pregnancy.

PMID- 16636774
TI  - Defining the position of deep inguinal ring in patients with indirect inguinal
      hernias.
AB  - A preliminary survey of surgeons of all grades in our hospital revealed confusion
      about the position of the deep inguinal ring. Standard teaching is that the deep
      inguinal ring is lateral to the femoral artery. The aim of this study was to
      define the position of the deep ring in patients undergoing elective inguinal
      hernia repair. Thirty consecutive male patients undergoing indirect inguinal
      hernia repair under local anaesthesia were studied. The following landmarks were
      marked on the patient with a felt pen: anterior superior iliac spine (ASIS),
      femoral artery (FA), deep inguinal ring (DR), pubic tubercle (PT) and pubic
      symphysis (PS). The distance of each point from the ASIS was measured in
      centimetres. The relation of the femoral artery to the deep inguinal ring was
      confirmed by palpation through the deep ring during surgery. The femoral artery
      was consistently identified midway between the anterior superior iliac spine and
      pubic symphysis (mid-inguinal point). The deep inguinal ring was located medial
      (22/30) or above (8/30) the femoral artery, but never lateral. The mean distances
      from the anterior superior iliac spine to the deep ring and femoral artery were
      8.8 and 7.7 cm, respectively. Contrary to standard teaching, this study
      demonstrates that the deep inguinal ring lies medial, not lateral, to the femoral
      artery. This may clarify some of the variations in textbook anatomy, and explain
      the difficulty in distinguishing direct and indirect inguinal hernias pre
      operatively.

PMID- 16636775
TI  - Landmarks of the facial nerve: implications for parotidectomy.
AB  - Facial nerve paralysis is a daunting potential complication of parotid surgery
      and is widely reported. Knowledge of the key landmarks of the facial nerve trunk
      is essential for safe and effective surgical intervention in the region of the
      parotid gland. In current practice, wide ranges of landmarks are used to identify
      the facial nerve trunk, however, there is much debate in the literature about the
      safety and reliability of each of these landmarks. The aim of this study,
      therefore, was to evaluate the relation of the surrounding anatomical structures
      and surgical landmarks to the facial nerve trunk. The anatomical relationship of
      the facial nerve trunk to the surrounding structures was determined after micro
      dissection on 40 adult cadavers. The shortest distances between the facial nerve
      and the "tragal pointer", attachment of the posterior belly of digastric muscle,
      tympanomastoid suture, external auditory canal, transverse process of the axis,
      angle of the mandible and the styloid process were measured. In addition, these
      distances were compared in the right and left sides, males and females and
      edentulous and non-edentulous mandibles. The distance of the facial nerve trunk
      from each of the surrounding landmarks ranged from (mm): tragal pointer, 24.3 to
      49.2 (mean 34); posterior belly of digastric, 9.7 to 24.3 (mean 14.6); external
      auditory canal, 7.3 to 21.9 (mean 13.4); tympanomastoid suture, 4.9 to 18.6 (mean
      10.0); styloid process, 4.3 to 18.6 (mean 9.8); transverse process of the axis,
      9.7 to 36.8 (mean 16.9); angle of the mandible, 25.3 to 48.69 (mean 38.1). The
      length of the facial nerve trunk from its point of exit from the stylomastoid
      foramen to its bifurcation into upper and lower divisions ranged from (mm) 8.6 to
      22.8 (mean 14.0). The results demonstrated that the posterior belly of digastric,
      tragal pointer and transverse process of the axis are consistent landmarks to the
      facial nerve trunk. However, it should be noted that the tragal pointer is
      cartilaginous, mobile, asymmetrical and has a blunt, irregular tip. This study
      advocates the use of the transverse process of the axis as it is easily palpated,
      does not require a complex dissection and ensures minimum risk of injury to the
      facial nerve trunk.

PMID- 16636777
TI  - Myosin-based contraction is not necessary for cardiac c-looping in the chick
      embryo.
AB  - During the initial phase of cardiac looping, known as c-looping, the heart bends
      and twists into a c-shaped tube with the convex outer curvature normally directed
      toward the right side of the embryo. Despite intensive study for more than 80
      years, the biophysical mechanisms that drive and regulate looping remain poorly
      understood, although some investigators have speculated that differential
      cytoskeletal contraction supplies the driving force for c-looping. The purpose of
      this investigation was to test this hypothesis. To inhibit contraction, embryonic
      chick hearts at stages 10-12 (10-16 somites, 33-48 h) were exposed to the myosin
      inhibitors 2,3-butanedione monoxime (BDM), ML-7, Y-27632, and blebbistatin.
      Experiments were conducted in both whole embryo culture and, to focus on bending
      alone, isolated heart culture. Measurements of heart stiffness and
      phosphorylation of the myosin regulatory light chains showed that BDM, Y-27632,
      and blebbistatin significantly reduced myocardial contractility, while ML-7 had a
      lesser effect. None of these drugs significantly affected looping during the
      studied stages. These results suggest that active contraction is not required for
      normal c-looping of the embryonic chick heart between stages 10 and 12.

PMID- 16636778
TI  - Quantitative detection of asbestos fiber in gravelly sand using elastic body
      exposure method.
AB  - Chrysotile or crocidolite colloidal solution containing donor plasmid DNA and
      Escherichia coli cells was subjected to elastic body friction. These acicular
      clay minerals mediated E. coli antibiotic resistance plasmid transformation.
      Other clay minerals had no effect on E. coli transformation. The number of E.
      coli transformants was counted after elastic body exposure with various
      crocidolite concentrations. There was a correlation between the number of E. coli
      transformants and crocidolite concentration (between 40 and 1,000 ng/ml). A
      mixture consisting of sea sand and crocidolite was utilized as a model for
      quantitative detection of asbestos in gravelly sand. With sea sand containing
      0.15-15 mg of crocidolite, a correlation between crocidolite concentration and
      the number of colonies derived from E. coli transformants was observed. This
      indicates that measurement of asbestos is possible even when the asbestos sample
      includes gravelly sand. Fluorescence microscopic observation of crocidolite
      colloidal solution indicated that crocidolite was present as spherical aggregates
      having diameters of 6-9 microm. Thus, the number of transformants correlated with
      that of 6-9 microm crocidolite aggregates.

PMID- 16636779
TI  - Gene transcription of neuroglobin is upregulated by hypoxia and anoxia in the
      brain of the anoxia-tolerant turtle Trachemys scripta.
AB  - Neuroglobin is a heme protein expressed in the vertebrate brain in mammals,
      fishes, and birds. The physiological role of neuroglobin is not completely
      understood but possibilities include serving as an intracellular oxygen-carrier
      or oxygen-sensor, as a terminal oxidase to regenerate NAD(+) under anaerobic
      conditions, or involvement in NO or ROS metabolism. As the vertebrate nervous
      system is particularly sensitive to hypoxia, an intracellular protein that helps
      sustain cellular respiration would aid hypoxic survival. However, the regulation
      of Neuroglobin (Ngb) under conditions of varying oxygen is controversial. This
      study examines the regulation of Ngb in an anoxia-tolerant vertebrate under
      conditions of hypoxia and anoxia. The freshwater turtle Trachemys scripta can
      withstand complete anoxia for days, and adaptations that permit neuronal survival
      have been extensively examined. Turtle neuroglobin specific primers were employed
      in RT-PCR for determining the regulation of neuroglobin mRNA expression in
      turtles placed in normoxia, hypoxia (4 h), anoxia (1 and 4 h), and anoxia
      reoxygenation. Whole brain expression of neuroglobin is strongly upregulated by
      hypoxia and post-anoxic-reoxygenation in T. scripta, with a lesser degree of
      upregulation at 1 and 4 h anoxia. Our data implicate neuroglobin in mediating
      brain anoxic survival.

PMID- 16636783
TI  - [Multislice CT in diagnostic work-up of polytrauma].
AB  - BACKGROUND: In severely injured patients, diagnostic procedures should be as
      brief as possible. With the use of spiral CT technology, the time required for
      diagnosis is minimized. QUESTION: Do severely injured patients benefit when
      primary diagnostic examinations are completed in less than 30 min? How much time
      is required for primary emergency department (ED) care and how much in the CT
      scanner? MATERIAL AND METHODS: Between 31 July 2001 and 31 December 2003,
      severely injured patients with ISS scores over 16 underwent total body spiral CT
      scans (Siemens Somatom Volume Zoom Multislice CT) after initial ultrasonography.
      One hundred patients (M:F=25:75) with an average age of 42 years (range: 3-81
      years) were evaluated retrospectively. The average ISS score was 32.8+/-12 points
      (range: 17-75 points). RESULTS: The average time in the ED, prior to CT, was 33+/
      14 min. The CT scans lasted 16+/-5 min and the total diagnostic time was 48+/-14
      min. Fifty percent of patients were taken immediately to the operating room. The
      mortality rate in hospital was 13%. The average hospital stay was 30 days, with
      an average ICU stay of 10 days. CONCLUSION: The shorter the time spent in the ED,
      the shorter the stays in ICU and in total hospitalization were, regardless of
      injury severity. With structured management and shortening of diagnostic time
      with spiral CT, the time in the ED was decreased from 85 to 48 min.

PMID- 16636787
TI  - Variability of motor potentials evoked by transcranial magnetic stimulation
      depends on muscle activation.
AB  - The purpose of this research was to determine whether motor cortex excitability
      assessed using transcranial magnetic stimulation (TMS) is less variable when
      subjects maintain a visually controlled low-level contraction of the muscle of
      interest. We also examined the dependence of single motor evoked potential (MEP)
      amplitude on stimulation intensity and pre-stimulus muscle activation level using
      linear and non-linear multiple regression analysis. Eight healthy adult subjects
      received single pulse TMS over the left motor cortex at a point where minimal
      stimulation intensity was required to produce MEPs in extensor digitorum communis
      (EDC). Voluntary activation of the muscle was controlled by visual display of a
      target force (indicated by a stable line on an oscilloscope) and the isometric
      force produced as the subject attempted to extend the fingers (indicated by a
      line on the oscilloscope representing the finger extension force) while subjects
      were instructed to: exert zero extension force (0%) and produce forces equal to 5
      and 10% of maximum voluntary finger extension under separate conditions. Relative
      variability (coefficient of variation) of single MEPs at a constant stimulus
      intensity and of pre-stimulus muscle EMG was lower during maintained 5 and 10%
      contractions than at 0% contraction levels. Therefore, maintaining a stable low
      intensity contraction helps stabilize cortical and spinal excitability. Multiple
      regression analyses showed that a linear dependence of single MEPs on stimulation
      intensity and pre-stimulus muscle activation level produced similar fits to those
      for a non-linear dependence on stimulus intensity and a linear dependence on pre
      stimulus EMG. Thus, a simple linear method can be used to assess dependence of
      single MEP amplitudes on both stimulus intensity (to characterize slope of the
      recruitment curve) and low intensity background muscle activation level.

PMID- 16636788
TI  - Brainstem and cerebellar fMRI-activation during horizontal and vertical
      optokinetic stimulation.
AB  - Animal studies have shown that not only cortical, but also brainstem and
      cerebellar areas are involved in the initiation and generation of optokinetic
      nystagmus (OKN), e.g., cortico-(pretecto)pontine-olivo-cerebellar pathways. The
      aim of this fMRI study was to identify and differentiate brainstem and cerebellar
      areas involved in horizontal and vertical OKN (h/vOKN) in humans. In a group of
      nine healthy volunteers, hOKN and vOKN were statistically compared with a
      stationary control condition. There were common activated regions for hOKN and
      vOKN directions located in the transition zone between the posterior thalamus and
      the mesencephalon bilaterally covering the pretectal nucleus complex, which is
      known to be a major structure within the afferent branch of the optokinetic
      system. Furthermore, during hOKN, activation occurred bilaterally in the
      mediodorsal and dorsolateral ponto-medullary brainstem, which could be best
      attributed to the reticular formation, especially the paramedian pontine
      reticular formation (PPRF). For vOKN, additional activated areas in the dorsal
      mesencephalic brainstem could be best localized to the ocular motor nuclei and
      the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF).
      For both OKN directions, the cerebellar activation was localized in the
      oculomotor vermis (declive VI, folium and tuber VIIA/B, in part pyramis VIIIA),
      and the flocculus bilaterally as well as widespread in the cerebellar
      hemispheres. In conclusion, fMRI allowed first attributions of neuronal
      substrates in the cerebellum and brainstem to hOKN and vOKN in humans. Consistent
      with the animal data, the dorsal ponto-medullary routes were involved bilaterally
      for hOKN, whereas the rostral mesencephalic routes were involved for vOKN.

PMID- 16636790
TI  - The mirror antisaccade task: direction-amplitude interaction and spatial accuracy
      characteristics.
AB  - In this study we examined the performance of human subjects in three oculomotor
      tasks: a visually guided saccade task (VST), a simple antisaccade task (SAT) and
      a mirror antisaccade task (MAT). The stimulus presentation was identical for all
      three tasks, and the differentiation of the tasks was based on the instruction
      given to the subjects. Subjects were instructed to either look at a visually
      presented target location (visually triggered saccade task), or to look at the
      opposite direction of the visually presented target (simple antisaccade task) or
      finally to look at the mirror location opposite to the location of the visually
      presented target (mirror antisaccade task). The loading of the simple antisaccade
      task with the addition of the amplitude requirement did not affect the percentage
      of directional errors but slowed down the onset of antisaccade execution by 19
      ms. The amplitude of the directionally correct antisaccade in the mirror
      antisaccade task showed a significant distortion of the true mirror target
      location. This dysmetria followed the same qualitative pattern to that observed
      for the visually guided saccades, i.e., a near-target hypermetria together with a
      far-target hypometria, but both these features were exaggerated in the mirror
      antisaccade task. This distorted amplitude modulation of mirror antisaccade
      amplitude was completely lost in corrected antisaccades that followed a
      directional error.

PMID- 16636791
TI  - Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic
      receptor: analysis in schizophrenia.
AB  - Cholinergic dysfunction is one of the hypotheses for the cognitive deficits of
      schizophrenia. Neurocognitive deficits, which are well-described clinical
      features of schizophrenia, may be remediated by nicotine; therefore
      investigations of nicotinic receptor subtypes is of considerable clinical
      interest. We typed polymorphisms in CHRNA4 and CHRNB2 genes controlling the
      expression of neuronal high-affinity nicotinic receptors in 117 Canadian families
      having at least one schizophrenic patient. Using a family-based association
      strategy, we performed allele, haplotype and interaction analysis of these two
      loci. In the families tested, the two cholinergic genes interact to affect
      schizophrenia in combination (P=0.010), while neither was sufficient alone to
      confer susceptibility. Our present study provided the first line of direct
      evidence suggesting that the CHRNA4 gene combined with CHRNB2 receptor gene may
      be linked to schizophrenia.

PMID- 16636792
TI  - Inhibitory control of reaching movements in humans.
AB  - Behavioral flexibility provides a very large repertoire of actions and
      strategies, however, it carries a cost: a potential interference between
      different options. The voluntary control of behavior starts exactly with the
      ability of deciding between alternatives. Certainly inhibition plays a key role
      in this process. Here we examined the inhibitory control of reaching arm
      movements with the countermanding paradigm. Right-handed human subjects were
      asked to perform speeded reaching movements toward a visual target appearing
      either on the same or opposite side of the reaching arm (no-stop trials), but to
      withhold the commanded movement whenever an infrequent stop signal was presented
      (stop trials). As the delay between go and stop signals increased, subjects
      increasingly failed to inhibit the movement. From this inhibitory function and
      the reaction times of movements in no-stop trials, we estimated the otherwise
      unobservable duration of the stopping process, the stop signal reaction time
      (SSRT). We found that the SSRT for reaching movements was, on average, 206 ms and
      that it varied with the reaching arm and the target position even though the stop
      signal was a central stimulus. In fact, subjects were always faster to withhold
      reaching movements toward visual targets appearing on the same side of the
      reaching arm. This behavior strictly parallels the course of the reaction times
      of no-stop trials. These data show that the stop and go processes interacting in
      this countermanding task are independent, but most likely influenced by a common
      factor when under the control of the same hemisphere. In addition, we show that
      the point beyond which the response cannot be inhibited, the so-called point-of
      no-return that divides controlled and ballistic phases of movement processing,
      lies after the inter-hemispheric transfer.

PMID- 16636793
TI  - Visual-tactile integration: does stimulus duration influence the relative amount
      of response enhancement?
AB  - Responses to multiple stimuli from different modalities tend to be faster
      compared to responses to each of these stimuli alone. Neurophysiological studies
      on higher mammals and behavioral studies on humans suggest that the relative
      amount of enhancement is inversely related to stimuli intensity. In two
      experiments the duration of visual and tactile stimuli was varied to investigate
      whether duration, as a further determinant of stimulus effectiveness, is also
      inversely related to the relative amount of response enhancement. Visual and
      tactile stimuli were presented left or right of fixation either in the same or
      different hemifields. Participants were required to gaze only at visual stimuli
      and to ignore tactile (focused attention paradigm). Saccadic reaction times were
      recorded. Results from both experiments show that the relative amount of response
      enhancement was largest for the shortest stimulus duration and decreases with
      increasing stimulus duration, i.e., inverse effectiveness of stimulus duration.

PMID- 16636794
TI  - Centrifugal regulation of a task-relevant somatosensory signal triggering
      voluntary movement without a preceding warning signal.
AB  - A warning signal followed by an imperative signal generates anticipatory and
      preparatory activities, which regulate sensory evoked neuronal activities through
      a top-down centrifugal mechanism. The present study investigated the centrifugal
      regulation of neuronal responses evoked by a task-relevant somatosensory signal,
      which triggers a voluntary movement without a warning signal. Eleven healthy
      adults participated in this study. Electrical stimulation was delivered to the
      right median nerve at a random interstimulus interval (1.75-2.25 s). The
      participants were instructed to extend the second digit of the right hand as fast
      as possible when the electrical stimulus was presented (ipsilateral reaction
      condition), or extend that of the left hand (contralateral reaction condition).
      They also executed repetitively extension of the right second digit at a rate of
      about 0.5 Hz, irrespective of electrical stimulation (movement condition), to
      count silently the number of stimuli (counting condition). In the control
      condition, they had no task to perform. The amplitude of short-latency
      somatosensory evoked potentials, the central P25, frontal N30, and parietal P30,
      was significantly reduced in both movement and ipsilateral reaction conditions
      compared to the control condition. The amplitude of long-latency P80 was
      significantly enhanced only in the ipsilateral reaction condition compared to the
      control, movement, contralateral reaction, and counting conditions. The long
      latency N140 was significantly enhanced in both movement and ipsilateral reaction
      conditions compared to the control condition. In conclusion, short- and long
      latency neuronal activities evoked by task-relevant somatosensory signals were
      regulated differently through a centrifugal mechanism even when the signal
      triggered a voluntary movement without a warning signal. The facilitation of
      activities at a latency of around 80 ms is associated with gain enhancement of
      the task-relevant signals from the body part involved in the action, whereas that
      at a latency of around 140 ms is associated with unspecific gain regulation
      generally induced by voluntary movement. These may be dissociated from the simple
      effect of directing attention to the stimulation.

PMID- 16636795
TI  - Changing plans: neural correlates of executive control in monkey and human
      frontal cortex.
AB  - Changing plans depends on executive control, the orchestration of behavior based
      on knowledge of both goal and context. Dorsolateral prefrontal (DLPFC) and
      anterior cingulate (ACC) cortices are clearly involved in these processes.
      Intracranial recordings in these regions were obtained from a monkey performing
      an executive control-challenging task that is widely used in clinic and
      laboratory to assess the integrity of cognitive function, the AX version of the
      continuous performance task (AX-CPT), and directly compared to scalp-recorded
      evoked potentials in humans. In this task the subject presses a button when
      detecting a frequent cue-target probe sequence in a stream of letters presented
      on a computer screen, and withholds response following incorrect sequences. Thus
      correct performance requires correct encoding of cue and probe instruction and
      inhibitory control. Intracranial recordings showed that DLPFC in the monkey was
      primarily activated by conditions that required inhibition of imminent action, as
      had been shown in human event-related potential (ERP) recordings. Different
      subregions of monkey ACC were activated primarily by either initiating or
      inhibiting action, whereas human ERP had shown ACC activation in both situations.
      We suggest that simultaneous activation of both types of subregions in conflict
      conditions may account the ubiquitous ACC activation observed with fMRI and ERP
      in those conditions.

PMID- 16636796
TI  - The role of action representations in visual object recognition.
AB  - It is typically assumed that perception for action and object recognition are
      subserved by functionally and neuroanatomically distinct processing streams in
      the brain. However, recent evidence challenges this classical view and suggests
      an interaction between both visual processing streams. While previous studies
      showed an influence of object perception on action-related tasks, we investigated
      whether action representations facilitate visual object recognition. In order to
      address this question, two briefly displayed masked objects were sequentially
      presented, either affording congruent or incongruent motor interactions. We found
      superior naming accuracy for object pairs with congruent as compared to
      incongruent motor interactions (Experiment 1). This action priming effect
      indicates that action representations can facilitate object recognition. We
      further investigated the nature of the representations underlying this action
      priming effect. The effect was absent when the prime stimulus was presented as a
      word (Experiment 2). Thus, the action priming effect seems to rely on action
      representations specified by visual object information. Our findings suggest that
      processes of object-directed action influence object recognition.

PMID- 16636797
TI  - Long lasting aftereffect of a single prism adaptation: Directionally biased shift
      in proprioception and late onset shift of internal egocentric reference frame.
AB  - We aimed to dissociate components in prism adaptation and its aftereffect by
      using prism adaptation training in healthy humans. Arm proprioceptive
      aftereffects are usually measured by indicating the subjective straight ahead
      direction with eyes closed (S). This measure however could be affected by other
      components besides proprioception, such as an efferent motor component and
      internal egocentric reference frame. Here we report a very long lasting
      proprioceptive shift, detected by two measuring methods, that is a component of
      the adaptation aftereffects to left wedge prism glasses. In order to minimize
      possible active motor components, arm passive proprioceptive midsagittal judgment
      was measured (P). The subject's arm was passively brought from the right or left
      lateral position, and stopped by subjects' verbal order. The results from these
      different measurements of midsagittal judgment were compared for 7 days after
      prism adaptation. Surprisingly, we found two distinctly separate aftereffects of
      proprioceptive shift depending on the directions of the passive arm movement. The
      shift of the midsagittal plane appeared only when tested from the left (Pl). This
      indicates that our strong prism adaptation procedure affected proprioception in a
      directionally biased way and not a spatially ubiquitous way. Further, the early
      aftereffect seen in active straight ahead pointing (S) was mostly similar to this
      biased shift in proprioception (Pl). However the long lasting aftereffect in
      straight ahead pointing was independently maintained up to day 7, when the
      passive proprioception had returned to pretest level. These results indicate that
      active straight ahead pointing (S) involves other components in addition to the
      passively measurable proprioceptive component. We suggest a late onset shift in
      the internal egocentric reference frame is involved in S. Possible neural
      mechanisms for these phenomena are discussed.

PMID- 16636798
TI  - Novel tetrahydroisoquinolin-ethyl-phenylamine based multidrug resistance
      inhibitors with broad-spectrum modulating properties.
AB  - PURPOSE: The ATP-binding cassette transporters P-glycoprotein (Pgp) and BCRP are
      implicated in multidrug resistance (MDR) of many tumors. Multi-targeted
      inhibitors such as cyclosporin A, have been shown to circumvent MDR in clinical
      trials. Here, we present the characterization of a novel class of effective and
      multi-targeted tetrahydroisoquinolin-ethyl-phenylamine based MDR inhibitors.
      METHODS: The novel MDR inhibitors, XR9577, WK-X-34, WK-X-50 and WK-X-84 were
      examined for cellular toxicity in several cell lines. Chemosensitivity and
      inhibition of BCRP-mediated mitoxantrone efflux were analyzed in BCRP
      overexpressing MCF7/mx cells. Chemosensitivity towards daunorubicin and
      inhibition of Pgp-mediated efflux of (99m)Tc-Sestamibi were examined in Pgp
      overexpressing A2780/Adr cells. Potential MRP-interactions were evaluated with 5
      CFDA efflux assays in selectively transfected MRP-1, -2 and -3 cell lines.
      RESULTS: All WK-X-compounds showed significant BCRP inhibition in the MCF7/mx
      cells resulting in significant increases in mitoxantrone intracellular
      accumulation and 200-300 fold increases in mitroxantrone cytotoxicity. WK-X-34
      and XR9577 were also potent inhibitors of Pgp, increasing (99m)Tc-Sestamibi
      accumulation with IC(50) values in the nM range. Daunorubicin cytotoxicity was
      also increased seven to eight-fold in cells co-treated with XR9577 or WK-X-34 (10
      muM). These compounds did not appear to interact with the MRP transporters. As
      compared to cyclosporin A, these compounds showed reduced cellular toxicity and
      increased potency of BCRP and Pgp inhibition. CONCLUSION: The novel MDR
      inhibitors WK-X-34 and XR9577 demonstrate superior effectiveness in Pgp and BCRP
      inhibition, in vitro tolerance and specificity over cyclosporin A. The novel
      compounds might be the promising candidates for a broad-spectrum based approach
      to the circumvention of MDR in resistant tumors.

PMID- 16636799
TI  - Negative results of an Italian Group for Mesothelioma (G.I.Me.) pilot study of
      single-agent imatinib mesylate in malignant pleural mesothelioma.

PMID- 16636800
TI  - Relationship between histologic thickness of tongue carcinoma and thickness
      estimated from preoperative MRI.
AB  - Several studies have shown that the thickness of tongue carcinoma is related to
      prognosis and to the likelihood of cervical node metastases. We investigated
      whether preoperative estimates of tumor thickness and volume, as determined from
      magnetic resonance imaging (MRI), correlated with histologic thickness and might
      therefore predict the presence of neck metastases. We assessed relationships
      between histologic tumor thickness and MRI tumor thickness and volume in a
      retrospective series of 33 patients with squamous cell carcinoma of the tongue.
      Thicknesses were determined by direct measurement and by considering corrections
      for ulceration or tumor vegetation (reconstructed thickness). Relationships
      between MRI thickness and the presence or absence of homolateral and
      contralateral nodal metastases were also investigated. We found that MRI
      thicknesses correlated strongly and directly with histologic tumor thicknesses,
      although mean MRI thicknesses were significantly greater than histologic
      thicknesses. MRI thicknesses were significantly greater in patients with
      contralateral neck involvement than in those with no neck involvement. We
      conclude that MRI provides an accurate and reproducible means of estimating the
      thickness of tongue carcinomas, paving the way for further studies on more
      extensive series of patients to determine whether preoperatively determined MRI
      thickness can reliably predict homolateral and bilateral neck involvement.

PMID- 16636801
TI  - Retinoblastoma - MR appearance using a surface coil in comparison with
      histopathological results.
AB  - PURPOSE: The purpose of this work was to evaluate the characteristic appearance
      of untreated retinoblastoma on a large sample in comparison to the histological
      findings after therapeutical enucleation. MATERIALS AND METHODS: In a prospective
      clinical trial 46 children with retinoblastoma in 63 affected untreated eyes were
      examined under general anesthesia on MRI using a 1.5-T system. The examinations
      were performed with a special surface coil applying an examination protocol
      including fast T2- and T1-weighted spin echo sequences and additional fast T1-WI
      after intravenous injection of Gd-DTPA in different planes. The imaging results
      were compared to the histopathological findings in 29 patients with 30 affected
      eyes. RESULTS: Comparing MRI findings and histopathological results, optic nerve
      infiltration was detected with a sensitivity of 53.8% and a specificity of 82.3%
      on MRI, infiltration of the choroid with a sensitivity of 75.0% and a specificity
      of 100.0%, and the degree of tumor calcification with a sensitivity of 91.7% and
      a specificity of 88.9%. In this study the characteristic MR appearance of
      untreated retinoblastoma was evaluated. CONCLUSION: MRI was helpful in relevant
      aspects of pretherapeutical retinoblastoma staging, deficits remain regarding
      optic nerve infiltration.

PMID- 16636802
TI  - CT colonography interpretation times: effect of reader experience, fatigue, and
      scan findings in a multi-centre setting.
AB  - Our purpose was to assess the effect of reader experience, fatigue, and scan
      findings on interpretation time for CT colonography. Nine radiologists
      (experienced in CT colonography); nine radiologists and ten technicians (both
      groups trained using 50 validated examinations) read 40 cases (50% abnormal)
      under controlled conditions. Individual interpretation times for each case were
      recorded, and differences between groups determined. Multi-level linear
      regression was used to investigate effect of scan category (normal or abnormal)
      and observer fatigue on interpretation times. Experienced radiologists (mean time
      10.9 min, SD 5.2) reported significantly faster than less experienced
      radiologists and technicians; odds ratios of reporting times 1.4 (CI 1.1, 1.8)
      and 1.6 (1.3, 2.0), respectively (P<or=0.001). Experienced and less-experienced
      radiologists took longer to report abnormal cases; ratio 1.2 (CI 1.1,1.4,
      P<0.001) and 1.2 (1.0, 1.3, P=0.03), respectively. All groups took 70% as long to
      report the final five cases as they did with an initial five; ratio 0.7 (CI 0.6
      to 0.8), P<0.001. For technicians only, accuracy increased with longer reporting
      times (P=0.04). Experienced radiologists report faster than do less-experienced
      observers and proportionally spend less time interpreting normal cases.
      Technicians who report more slowly are more accurate. All groups reported faster
      as the study period progressed.

PMID- 16636803
TI  - Polyp measurement and size categorisation by CT colonography: effect of observer
      experience in a multi-centre setting.
AB  - The extent measurement error on CT colonography influences polyp categorisation
      according to established management guidelines is studied using twenty-eight
      observers of varying experience to classify polyps seen at CT colonography as
      either 'medium' (maximal diameter 6-9 mm) or 'large' (maximal diameter 10 mm or
      larger). Comparison was then made with the reference diameter obtained in each
      patient via colonoscopy. The Bland-Altman method was used to assess agreement
      between observer measurements and colonoscopy, and differences in measurement and
      categorisation was assessed using Kruskal-Wallis and Chi-squared test statistics
      respectively. Observer measurements on average underestimated the diameter of
      polyps when compared to the reference value, by approximately 2-3 mm,
      irrespective of observer experience. Ninety-five percent limits of agreement were
      relatively wide for all observer groups, and had sufficient span to encompass
      different size categories for polyps. There were 167 polyp observations and 135
      (81%) were correctly categorised. Of the 32 observations that were
      miscategorised, 5 (16%) were overestimations and 27 (84%) were underestimations
      (i.e. large polyps misclassified as medium). Caution should be exercised for
      polyps whose colonographic diameter is below but close to the 1-cm boundary
      threshold in order to avoid potential miscategorisation of advanced adenomas.

PMID- 16636804
TI  - Integrated cardio-thoracic imaging with ECG-Gated 64-slice multidetector-row CT:
      initial findings in 133 patients.
AB  - The purpose of this study was to investigate the possibility of assessing the
      underlying respiratory disease as well as cardiac function during ECG-gated CT
      angiography of the chest with 64-slice multidetector-row CT (MDCT). One hundred
      thirty-three consecutive patients in sinus rhythm with known or suspected
      ventricular dysfunction underwent an ECG-gated CT angiographic examination of the
      chest without beta-blockers using the following parameters: (1) collimation: 32 x
      0.6 mm with z-flying focal spot for the acquisition of 64 overlapping 0.6-mm
      slices (Sensation 64; Siemens); rotation time: 0.33 s; pitch: 0.3; 120 kV; 200
      mAs; ECG-controlled dose modulation (ECG-pulsing) and (2) 120 ml of a 35%
      contrast agent. Data were reconstructed: (1) to evaluate the underlying
      respiratory disease (1-mm thick lung and mediastinal scans reconstructed at 55%
      of the R-R interval; i.e., "morphologic scans") and (2) to determine right (RVEF)
      and left (LVEF) ventricular ejection fractions (short-axis systolic and diastolic
      images; Argus software; i.e., "functional scans"). The mean heart rate was 73 bpm
      (range: 42-120) and the mean scan time was 18.11 +/- 2.67 s (range: 10-27). A
      total of 123 examinations (92%) had both lung and mediastinal images rated as
      diagnostic scans, whereas 10 examinations (8%) had non-diagnostic images altered
      by the presence of respiratory-motion artifacts (n = 4) or cyclic artifacts
      related to the use of a pitch value of 0.3 in patients with a very low heart rate
      during data acquisition (n = 6). Assessment of right and left ventricular
      function was achievable in 124 patients (93%, 95% CI: 88-97%). For these 124
      examinations, the mean RVEF was 46.10% (+/- 9.5; range: 20-72) and the mean LVEF
      was 58.23% (+/- 10.88; range: 20-83). In the remaining nine patients, an
      imprecise segmentation of the right and left ventricular cavities was considered
      as a limiting factor for precise calculation of end-systolic and end-diastolic
      ventricular volumes. The mean (+/- SD) DLP value of the examinations was 279.86
      (+/- 117.50) mGy.cm. Assessment of underlying respiratory disease and cardiac
      function from the same data set was achievable in 92% of the patients with ECG
      gated 64-slice MDCT.

PMID- 16636810
TI  - Treatment with HPMA copolymer-based doxorubicin conjugate containing human
      immunoglobulin induces long-lasting systemic anti-tumour immunity in mice.
AB  - Linkage of doxorubicin (Dox) to a water-soluble synthetic N-(2
      hydroxypropyl)methacrylamide copolymer (PHPMA) eliminates most of the systemic
      toxicity of the free drug. In EL-4 lymphoma-bearing C57BL/6 mice, a complete
      regression of pre-established tumours has been achieved upon treatment with Dox
      PHPMA-HuIg conjugate. The treatment was effective using a range of regimens and
      dosages, ranging from 62.5 to 100% cured mice treated with a single dose of 10-20
      mg of Dox eq./kg, respectively. Fractionated dosages producing lower levels of
      the conjugate for a prolonged time period had substantial curative capacity as
      well. The cured mice developed anti-tumour protection as they rejected
      subsequently re-transplanted original tumour. The proportion of tumour-protected
      mice inversely reflected the effectiveness of the primary treatment. The
      treatment protocol leading to 50% of cured mice produced only protected mice,
      while no mice treated with early treatment regimen (i.e. starting on day 1 after
      tumour transplantation) rejected the re-transplanted tumour. Exposure of the host
      to the cancer cells was a prerequisite for developing protection. The anti-tumour
      memory was long lasting and specific against the original tumour, as the cured
      mice did not reject another syngeneic tumour, melanoma B16-F10. The immunity was
      transferable to naive recipients in in vivo neutralization assay by spleen cells
      or CD8(+) lymphocytes derived from cured animals. We propose an effective
      treatment strategy which eradicates tumours without harming the protective immune
      anti-cancer responses.

PMID- 16636811
TI  - Soluble MICB in malignant diseases: analysis of diagnostic significance and
      correlation with soluble MICA.
AB  - Expression of ligands of the immunoreceptor NKG2D such as MICA and MICB has been
      proposed to play an important role in the immunosurveillance of tumors.
      Proteolytic shedding of NKG2D ligands from cancer cells therefore constitutes an
      immune escape mechanism impairing anti-tumor reactivity by NKG2D-bearing
      cytotoxic lymphocytes. Serum levels of sMICA have been shown to be of diagnostic
      significance in malignant diseases of various origins. Here, we investigated the
      potential of soluble MICB, the sister molecule of MICA, as a marker in cancer and
      its correlation with soluble MICA. Analysis of MICB in sera of 512 individuals
      revealed slightly higher MICB levels in patients with various malignancies (N =
      296; 95th percentile 216 pg/ml; P = 0.069) than in healthy individuals (N = 62;
      95th percentile 51 pg/ml). Patients with benign diseases (N = 154; 95th
      percentile 198 pg/ml) exhibited intermediate MICB levels. In cancer patients,
      elevated MICB levels correlated significantly with cancer stage and metastasis (P
      = 0.007 and 0.007, respectively). Between MICB and MICA levels, only a weak
      correlation was found (r = 0.24). Combination of both markers resulted only in a
      slightly higher diagnostic power in the high specificity range. The reduction of
      MICA and MICB surface expression on cells by shedding and the effects of sMICA
      and sMICB in serum on host lymphocyte NKG2D expression might play a role in late
      stages of tumor progression by overcoming the confining effect of NK cells and
      CD8 T cells. While MICB levels are not suited for the diagnosis of cancer in
      early stages, they may provide additional information for the staging of cancer
      disease.

PMID- 16636812
TI  - Target-selective activation of a TNF prodrug by urokinase-type plasminogen
      activator (uPA) mediated proteolytic processing at the cell surface.
AB  - We have previously developed TNF prodrugs comprised of a N-terminal scFv
      targeting, a TNF effector and a C-terminal TNFR1-derived inhibitor module linked
      to TNF via a MMP-2 motif containing peptide, allowing activation by MMP-2
      expressing tumor cells. To overcome the known heterogeneity of matrix
      metalloprotease expression, we developed TNF prodrugs that become processed by
      other tumor and/or stroma-associated proteases. These TNF prodrugs comprise
      either an uPA-selective or a dual uPA-MMP-2-specific linker which displayed
      efficient, target-dependent and cleavage sequence-specific activation by the
      corresponding tumor cell-expressed proteases. Selective pharmacologic inhibition
      of endogenous uPA and MMP-2 confirm independent prodrug processing by these two
      model proteases and indicate the functional superiority of a prodrug containing a
      multi-specific protease linker. Processing optimised TNF prodrugs should increase
      the proportion of active therapeutic within the targeted tissue and thus
      potentially enhance tumor response rate.

PMID- 16636813
TI  - Chylothorax, an unusual mechanical complication after central venous cannulation
      in children.

PMID- 16636814
TI  - Plasma antithrombin III and protein C levels in early recognition of late-onset
      sepsis in newborns.
AB  - OBJECTIVE: The aim of this prospective, observational study was to establish the
      prognostic values of plasma antithrombin III (ATIII) and protein C (PC)
      functional levels, determined in 150 neonates with suspected late-onset sepsis.
      OBSERVATIONS: Both the ATIII and PC concentrations were significantly lower in
      neonates with sepsis, either confirmed or not confirmed by blood culture, than
      data obtained in infants with excluded disease. The lowest values of plasma ATIII
      and PC were observed in neonates who had died in the course of sepsis. The
      differences between survivors and non-survivors were statistically significant
      (respectively, for ATIII P=0.003 and for PC P=0.00002). A highly statistically
      significant correlation (P=0.0016) between plasma PC functional level and risk of
      death was found in patients with sepsis. However, plasma ATIII concentration,
      evaluated in the same group of patients, did not correlate with the occurrence of
      death. CONCLUSION: We concluded that the measurement of plasma ATIII and,
      especially, PC levels may facilitate the recognition of sepsis and, with respect
      to PC, may have a prognostic value. Plasma PC functional concentration below 10%
      might be the indication for supplementation of PC concentrate.

PMID- 16636815
TI  - Characteristics of brachial-ankle pulse wave velocity in Japanese children.
AB  - BACKGROUND: Measurement of pulse wave velocity (PWV) is a useful approach for
      evaluating the severity of atherosclerosis in adults, and, in particular, the
      measurement of brachial-ankle PWV (baPWV) has been commonly reported as a simple
      and practicable method. We attempted to investigate how baPWV in healthy children
      changes with age and gender, in order to assess baPWV in children with risk
      factors for the early progression of systemic atherosclerosis. METHODS: We
      measured baPWV in 970 healthy Japanese children (500 boys and 470 girls), and set
      up the normal baPWV values of children on the basis of age and gender. We also
      performed linear regression analysis and step-wise multiple regression analysis
      for evaluating its correlation with baPWV and independent variables for baPWV in
      children. RESULTS: The values of baPWV in children were higher in boys than in
      girls, and baPWV increased with age in both genders. Age, blood pressure and
      heart rate (HR) were significant determinants of baPWV in both male and female
      subjects, while the obesity index had no correlation with baPWV. CONCLUSION: On
      the basis of these results, we suggest that baPWV in children is largely
      influenced by age and gender, and that baPWV gradually increased with age in both
      genders.

PMID- 16636816
TI  - Back education in elementary schoolchildren: the effects of adding a physical
      activity promotion program to a back care program.
AB  - Promoting a physically active lifestyle whilst optimizing the spinal load at a
      young age seems to be advocated within the scope of early back pain prevention
      efforts. The present study aimed at evaluating the effects of combining a back
      care program with a physical activity promotion program in elementary
      schoolchildren. In a pre-post design over two school years, back care knowledge,
      back care behavior, fear avoidance beliefs and back pain reports were evaluated
      in children classified into three categories--those who received a back care and
      a physical activity promotion program (n=190), those who received only a back
      care program (n=193) and those in a control group (n=172) (mean age at baseline:
      9.7 years+/-0.7). Physical activity levels were evaluated in a sub-sample of 26
      pupils in each group. The back care program and the physical activity promotion
      program were both comprehensive ones. In both intervention groups, the scores for
      back care related knowledge and back care behavior were significantly higher than
      the control group. The increase in the sum score for back care behavior was
      significantly higher in the back care group than in the back care plus physical
      activity promotion group. Significant interaction effects showed an increase in
      fear-avoidance beliefs between pre- and post-tests in the control group,
      significantly different from the better scores in both intervention groups.
      Interaction effects were not significant for pain reports. In the back care plus
      physical activity promotion group, the daily moderate to vigorous physical
      activity levels decreased by 8 min per day while a decrease by 31 min per day was
      found in the back care group and a decrease by 36 min per day in the control
      group. However, group differences were not significant. The present study
      findings favor the addition of a physical activity promotion program to a back
      care program in elementary schools within the scope of early back pain prevention
      efforts. However, the findings also emphasize the disadvantages of implementing
      both programs simultaneously in a school curriculum that is already full.

PMID- 16636822
TI  - Fusarium graminearum-induced changes in gene expression between Fusarium head
      blight-resistant and susceptible wheat cultivars.
AB  - Fusarium head blight (FHB), primarily caused by Fusarium graminearum Schw., is a
      destructive disease of wheat (Triticum aestivum L.). Although several genes
      related to FHB resistance have been reported, global analysis of gene expression
      in response to FHB infection remains to be explored. The expression patterns of
      transcriptomes from wheat spikes of FHB-resistant cultivar Ning 7840 and
      susceptible cultivar Clark were monitored during a period of 72 h after
      inoculation (hai) with F. graminearum. Microarray analysis, coupled with
      suppression subtractive hybridization technique, identified 44 significantly
      differentially expressed genes between cv. Ning 7840 and cv. Clark. More
      differentially expressed genes were identified from susceptible libraries than
      from resistance libraries. The up-regulation of defense-related genes in Ning
      7840 relative to cultivar Clark occurred during early fungal stress (3-12 hai).
      Three genes, with unknown function that were up-regulated in cv. Ning 7840 at
      most time points investigated, might play an important role in enhancing FHB
      resistance.

PMID- 16636823
TI  - Staying alive in adversity: transcriptome dynamics in the stress-resistant dauer
      larva.
AB  - In response to food depletion and overcrowding, the soil nematode Caenorhabditis
      elegans can arrest development and form an alternate third larval stage called
      the dauer. Though nonfeeding, the dauer larva is long lived and stress resistant.
      Metabolic and transcription rates are lowered but the transcriptome of the dauer
      is complex. In this study, distribution analysis of transcript profiles generated
      by Serial Analysis of Gene Expression (SAGE) in dauer larvae and in mixed
      developmental stages is presented. An inverse relationship was observed between
      frequency and abundance/copy number of SAGE tag types (transcripts) in both
      profiles. In the dauer profile, a relatively greater proportion of highly
      abundant transcripts was counterbalanced by a smaller fraction of low to
      moderately abundant transcripts. Comparisons of abundant tag counts between the
      two profiles revealed relative enrichment in the dauer profile of transcripts
      with predicted or known involvement in ribosome biogenesis and protein synthesis,
      membrane transport, and immune responses. Translation-coupled mRNA decay is
      proposed as part of an immune-like stress response in the dauer larva. An
      influence of genomic region on transcript level may reflect the coordination of
      transcription and mRNA turnover.

PMID- 16636827
TI  - Joint use of small-angle X-ray and neutron scattering to study biological
      macromolecules in solution.
AB  - Novel techniques for simultaneous analysis of X-ray and neutron scattering
      patterns from macromolecular complexes in solution are presented. They include ab
      initio shape and internal structure determination of multicomponent particles and
      more detailed rigid body modeling of complexes using high resolution structures
      of subunits. The methods fit simultaneously X-ray and neutron scattering curves
      including contrast variation data sets from selectively deuterated complexes.
      Biochemically sound interconnected models without steric clashes between the
      components displaying a pre-defined symmetry are generated. For rigid body
      modeling, distance restraints between specified residues/nucleotides or their
      ranges are taken into account. The efficiency of the methods is demonstrated in
      model examples, and potential sources of ambiguity are discussed.

PMID- 16636828
TI  - Enhancing insecticidal efficacy of baculovirus by early expressing an insect
      neurotoxin, LqhIT2, in infected Trichoplusia ni larvae.
AB  - LqhIT(2), an insect specific neurotoxin from the venom of Leiurus quinquestriatus
      hebraeus, has been demonstrated to improve insecticidal efficacy of Autographa
      californica nuclear polyhedrosis virus (AcMNPV). A polyhedrin-positive
      recombinant AcMNPVvAcP(hsp70)EGFP/P(pag90)IT(2) was engineered for larvae to
      express the enhanced green fluorescence protein (EGFP) and LqhIT(2) under the
      control of P(hsp70) and P(pag90) promoters, respectively. This would allow a
      visual observation of the viral infection and an improvement of the insecticidal
      efficacy. The insecticidal activity of this recombinant baculovirus, a wild type
      AcMNPV and four other recombinant baculoviruses, was evaluated and compared in
      terms of mortality, body weight, median lethal time (LT(50)), and median lethal
      concentration (LC(50)). Insecticidal efficacy was unaltered when treated with
      vAcP(hsp70)EGFP, moderately improved when infected by vAcP(10)IT(2) (a P(10)
      promoted LqhIT ( 2 ) gene), and significantly elevated when treated with
      vAcP(pag90)IT(2) or vAcP(hsp70)EGFP/P(pag90)IT(2). No apparent difference was
      observed in insecticidal efficacy when additional EGFP was expressed as a visible
      marker. These results suggest that recombinant AcMNPV
      vAcP(hsp70)EGFP/P(pag90)IT(2) may be used as an effective insecticide against
      Trichoplusia ni and other lepidopterous insect pests.

PMID- 16636829
TI  - Stable expression of bioactive recombinant pleurocidin in a fish cell line.
AB  - Pleurocidin (Ple), a linear cationic peptide of 25 amino acids, is a member of a
      larger family of antimicrobial peptides present in flatfish. Previous studies
      have shown that Ple displays a strong antimicrobial activity against a broad
      spectrum of bacteria and appears to play a role in innate host defence. In this
      work, the genomic sequence encoding the Ple prepropeptide has been isolated from
      Limanda limanda and cloned in a vector under the control of a non-viral promoter
      (the carp beta-actin promoter). By using this construction, expression of
      bioactive Ple was demonstrated in transformed fish cell lines continuously
      growing for more than 2 years. Furthermore, the study of Ple processing,
      maturation and secretion (by using fusion with green fluorescence protein) and
      the high bactericidal activity of the secreted recombinant Ple (detectable in
      cell supernatants without any concentration) are all reported here, as no other
      recombinant Ple or fish antimicrobial peptide have been expressed before to that
      extent. Such an overexpression of recombinant Ple or any other related
      antimicrobial peptide might improve the chances to develop new antibiotic agents,
      as well as to provide essential information about the mechanism of action, range
      of activity and the role in the innate immune response of antibiotic peptides.

PMID- 16636830
TI  - Therapeutic effect of llama derived VHH fragments against Streptococcus mutans on
      the development of dental caries.
AB  - Streptococcus mutans is the main cause of dental caries. We evaluated the
      therapeutic effect of variable regions of a llama heavy chain antibody fragments
      directed against S. mutans named S36-VHH (S for Streptococcus) alone or fused
      with glucose oxidase (GOx) from Aspergillus niger. Western blot analysis and
      ELISA revealed binding of the S36-VHH to the streptococcal antigen I/II adhesin
      molecule of S. mutans serotype C. In a rat-desalivated caries model, daily
      administration of S36-VHH significantly reduced the development of smooth surface
      caries. No additional therapeutic effect of GOx was observed. Our results suggest
      that llama VHH antibodies may be a potential benefit as prophylaxis against
      dental caries.

PMID- 16636831
TI  - Cloning and heterologous expression of the exo-beta-D-glucosaminidase-encoding
      gene (gls93) from a filamentous fungus, Trichoderma reesei PC-3-7.
AB  - We have previously reported on purification and characterization of an exo-beta-D
      glucosaminidase (Gls93) from culture filtrate of Trichoderma reesei PC-3-7 grown
      on N-acetyl-D-glucosamine (GlcNAc). The corresponding gene of Gls93 was cloned
      and characterized in this work. To our knowledge, this is the first report on
      cloning of the gene encoding fungal exo-beta-D-glucosaminidase. This gene has no
      introns and encodes a polypeptide of 892 amino acids (aa) containing a secretion
      signal of 28 amino acids. Comparison of the amino acid sequence to known proteins
      and phylogenetic analysis indicated that gls93 belongs to the glycoside hydrolase
      family (GHF) 2 and should be further classified into a new subgroup, exo-beta-D
      glucosaminidase subgroup. The gls93 transcription was biphasic when T. reesei was
      grown on GlcNAc, suggesting that the expression of this gene may be regulated by
      a complex mechanism, in which multiple regulatory proteins are involved.
      Furthermore, gls93 could be expressed in Pichia pastoris (ca. 0.49-mg/ml
      culture). The recombinant Gls93 had the two molecular forms, ca. 105 and 100 kDa,
      whose difference is caused by N-glycosylation. Both of them had the same
      properties such as specific activity and substrate specificity and showed only
      the activity of exo-beta-D-glucosaminidase but not those of beta-galactosidase,
      beta-glucuronidase, and beta-mannosidase belonging to GHF2.

PMID- 16636832
TI  - A laccase from the medicinal mushroom Ganoderma lucidum.
AB  - A protein demonstrating laccase activity and potent inhibitory activity towards
      human immunodeficiency virus (HIV)-1 reverse transcriptase (IC50 1.2 microM) was
      isolated from fresh fruiting bodies of the medicinal mushroom Ganoderma lucidum.
      The laccase had a novel N-terminal sequence and a molecular mass of 75 kDa, which
      is higher than the range (55-56 kDa) reported for most other mushroom laccases.
      It was isolated by sequential chromatography on DEAE-cellulose and Affi-gel blue
      gel and adsorption on Con A-Sepharose. Unlike some of the previously isolated
      laccases, it was adsorbed only on Con A-Sepharose. The enzyme required a pH of 3
      5 and a temperature of 70 degrees C to exhibit maximal activity. Minimal activity
      was detected at pH 6 and 7. Activity was undetectable at pH 8 and 9 and after
      exposure to 100 degrees C for 10 min.

PMID- 16636833
TI  - Evidence for proteins involved in prophenoloxidase cascade Eisenia fetida
      earthworms.
AB  - The prophenoloxidase cascade represents one of the most important defense
      mechanisms in many invertebrates. Following the recognition of microbial
      saccharides by pattern recognition molecules, proteinases cleave inactive
      prophenoloxidase to its active form, phenoloxidase. Phenoloxidase is a key enzyme
      responsible for the catalysis of the melanization reaction. Final product melanin
      is involved in wound healing and immune responses. Prophenoloxidase cascade has
      been widely described in arthropods; data in other invertebrate groups are less
      frequent. Here we show detectable phenoloxidase activity in 90-kDa fraction of
      the coelomic fluid of earthworms Eisenia fetida. Amino acid sequencing of
      peptides from the active fraction revealed a partial homology with invertebrate
      phenoloxidases and hemocyanins. Moreover, the level of phenoloxidase activity is
      lower and the activation slower as compared to other invertebrates.

PMID- 16636835
TI  - Uveal melanoma in young patients.
AB  - INTRODUCTION: This study aimed to investigate the clinical profile of young
      patients with uveal melanoma treated in 1995-2002 in the Department of
      Ophthalmology, Jagiellonian University, Krakow, Poland. METHODS: Retrospective
      case-control series. RESULTS: Out of 800 patients with uveal melanoma treated
      between 1995 and 2002, there were 11 patients (1.4%) aged 20 or younger. The mean
      age of those patients was 17.9 (12-20, median 19) years. There were five men
      (45%) and six women (55%). In all cases, the tumor was unilateral. In five (45%)
      cases the tumor affected the right eye and in six (55%) cases the left eye. Eight
      (72%) patients were treated with local resection. Among these, eight patients, in
      two (18%) with iris or ciliary body melanoma we used adjuvant Ru-106 episcleral
      plaque brachytherapy (EPB). In two (18%) cases of choroidal melanoma, we
      performed I-125 EPB: one case ended with regression of the tumor, while the
      second did not respond to EPB and we had to enucleate the eye. In one (9%) case
      we performed enucleation as the primary treatment. The mean follow-up was 61.4
      months, ranging 30-125 months. All those patients are still alive and no
      metastases were detected. CONCLUSIONS: Uveal melanoma is a rare malignancy in
      children and teenagers. In the present series, it occurred in the iris in more
      than 50% of cases.

PMID- 16636836
TI  - Endothelial cell density in porcine corneas after exposure to hypotonic
      solutions.
AB  - PURPOSE: To evaluate exposure to sucrose solution (1.8%) and hypotonic balanced
      salt solution (BSS) for its effects on endothelial cell density of porcine
      corneas. METHODS: Two groups of central discs from pig corneas were organ
      cultured for 24 h. Twelve corneas per group were exposed to sucrose solution
      (1.8%) or hypotonic BSS for 4 min each. The paired corneal discs were not treated
      and served as controls. After further organ culture with and without dextran for
      48 h, corneal endothelium was stained with alizarin red and examined by light
      microscopy. The endothelial cell densities were determined manually on three
      central images. RESULTS: The endothelial cell density differed significantly
      between corneas exposed to sucrose and the control corneas (3982+/-382
      cells/mm(2) and 4360+/-331 cells/mm(2) respectively, and 3876+/-364 cells/mm(2)
      versus 4374+/-168 cells/mm(2) respectively with 6% dextran). In contrast, the
      endothelial cell density did not differ significantly between corneas exposed to
      hypotonic BSS and the control corneas (4374+/-296 cells/mm(2) and 4317+/-193
      cells/mm(2) respectively, and 4348+/-151 cells/mm(2) versus 4426+/-175
      cells/mm(2), respectively with 6% dextran). CONCLUSIONS: Exposure to 1.8% sucrose
      for 4 min induces a significant endothelial cell loss of 10% on average, whereas
      exposure to hypotonic BSS did not significantly influence the endothelial cell
      density.

PMID- 16636837
TI  - Patients prefer once-daily glaucoma drops.
AB  - BACKGROUND: The relationship between complexity of eye drop regime and compliance
      is not straightforward, i.e. fewer drops may not mean better compliance. We
      investigated the level of inconvenience different eye drop regimes incurred in
      comparison with a once-daily (OD) regime for patients experienced with using
      topical anti-glaucoma medication. METHODS: Patients indicated the level of
      inconvenience from drop regimes of 1, 2, 3 or 4 times daily on 10-cm visual
      analogue scales. The score for the OD regime was then compared with the scores
      for the other regimes using paired t-tests with Bonferroni correction. RESULTS:
      At a significance limit of p = 0.05, five of six subgroups indicated once-a-day
      drops were significantly more convenient than other regimes. Patients who had
      used the OD regime considered this difference greater than those who had not.
      CONCLUSIONS: This study's results offer some pragmatic guidance on choice of
      therapy and on counselling patients about compliance. We would suggest starting
      patients on OD drops in preference to alternatives to promote compliance.

PMID- 16636838
TI  - Behavior of retinal epithelium to bleb detachment versus retinectomy.
AB  - PURPOSE: To compare the behavior of the retinal pigment epithelium to a bleb
      detachment versus removal of a segment of neural retina. METHODS: A bleb
      detachment was performed on 14 adult pigmented rabbits. In seven rabbits, the
      neural retina was removed within the bleb detachment. The rabbits were followed
      for months after surgery by scanning laser ophthalmoscopy and post mortem
      histology using light and electron microscopy. RESULTS: Bleb detachment produces
      a transformation of the retinal epithelial layer that results in migration,
      enlargement of cell size and accumulation of large amounts of lysosomal material,
      resembling that found in Chediak-Higashi syndrome. Retinectomy causes migration
      of the epithelial cells, development of multiple layers with vacuoles but no
      accumulation of lysosomal material. CONCLUSION: The neural retina appears to
      exert a strong influence on the behavior of the retinal epithelial layer. Brief
      separation of the neural retina from the epithelium provokes a rapid
      transformation of this cell layer leading to migration of the cells and apparent
      faulty digestion of phagosomes, causing an enormous buildup of lysosomal debris.
      Removal of the neural retina also provokes retinal epithelial cell migration but
      no buildup of lysosomal debris occurs, presumably due to the absence of
      photoreceptor outer segments and consequently phagosomes. This migratory
      tendency, which appears to alter lysosomal degradation, could lead to apoptosis
      of these epithelial cells.

PMID- 16636839
TI  - Digital imaging in differential diagnosis of small choroidal melanoma.
AB  - BACKGROUND: To assess the role of digital imaging and a new subtraction method
      for differential diagnosis of choroidal nevus and small choroidal melanoma.
      METHODS: Of 241 consecutive patients referred to a tertiary referral center for
      suspected choroidal melanoma, 110 who underwent digital imaging of the ocular
      fundus were eligible for this study. Digital color, red-free and red light
      retinal images were evaluated in a randomized and masked manner and by the
      subtraction method for diagnosis of the fundus lesion. The reference standard was
      based on the combined results of ophthalmological examination, including
      mydriatic ophthalmoscopy, B scan ultrasonography, digital imaging and fluorescein
      angiography of the ocular fundus. RESULTS: Comparative use of digital color, red
      free and red light imaging had 85.7% (95%CI 42.1-99.6) sensitivity, 99.0% (95%CI
      94.7-99.9) specificity and 98.2% (95%CI 93.6-99.8) exact agreement versus
      reference standard in differentiation of small choroidal melanoma from
      pseudomelanoma. Direct comparison between use of digital images and the reference
      standard showed excellent agreement in detecting small choroidal melanoma from
      suspected choroidal lesions (K 0.847; 95%CI 0.639-1.0). The subtraction method
      was useful to show growth in four of 94 melanocytic choroidal tumors. The mean
      annual incidence of choroidal melanoma in Southwest Finland was 0.80 per 100.000
      population. The most frequent choroidal pseudomelanomas were choroidal melanotic
      and amelanotic nevi, disciform lesions, congenital hypertrophy of the retinal
      pigment epithelium, and circumscribed choroidal hemangioma. CONCLUSIONS: Combined
      use of digital color, red-free and red light imaging was a suitable adjunct in
      differentiation of small choroidal melanoma from different pseudomelanomas. The
      subtraction method may reveal early growth of the melanotic choroidal tumors.

PMID- 16636840
TI  - Detection of motion onset and offset: reaction time and visual evoked potential
      analysis.
AB  - Manual reaction time (RT) and visual evoked potentials (VEP) were measured in
      motion onset and offset detection tasks. A considerable homology was observed
      between the temporal structure of RTs and VEP intervals, provided that the change
      in motion was detected as soon as the VEP signal has reached critical threshold
      amplitude. Both manual reactions and VEP rise in latency as the velocity of the
      onset or offset motion decreases and were well approximated by the same negative
      power function with the exponent close to -2/3. This indicates that motion
      processing is normalised by subtracting the initial motion vector from ongoing
      motion. A comparison of the motion onset VEP signals in two different conditions,
      in one of which the observer was instructed to abstain from the reaction and in
      the other to indicate as fast as possible the beginning of the motion, contained
      accurate information about the manual response.

PMID- 16636841
TI  - Item-specific congruency effects in nonverbal auditory Stroop.
AB  - In the current study, participants judged as 'low' or 'high' either the location
      or the frequency of a single tone presented in one of two locations at one of two
      frequencies. The classification associated with the irrelevant feature could be
      either congruent or incongruent with the required response. The results of
      Experiment 1 revealed that responses were made more slowly on incongruent than on
      congruent trials, regardless of whether participants judged sounds according to
      their location or their pitch. In Experiment 2, we manipulated the probability
      that the classification associated with the irrelevant acoustic feature was
      consistent with the classification associated with the task-relevant dimension.
      In this experiment responses were made more quickly on congruent trials when the
      response associated with the irrelevant feature was likely to be consistent with
      the required response, and on incongruent trials when the response associated
      with the irrelevant feature was likely to be inconsistent with the required
      response.

PMID- 16636842
TI  - A QCAR-approach to materials modeling.
AB  - Little is known about the relationship between the function and structure of
      materials. Materials (solids with a function) are complex entities and a better
      knowledge of the parameters that contribute to function is desirable. Here, we
      present modeling approaches that correlate chemical composition with function of
      heterogeneous catalysts. The complete composition space of the mixed oxides of Ni
      Cr-Mn and of Ni-Co-Mo-Mn (10% spacing) have been measured for the oxidation of
      propene to acroleine. The data have been collected, visualized and modeled.
      Different mathematical approaches such as Support Vector Machines, multilevel B
      splines approximation and Kriging have been applied to model this relationship.
      High-throughput screening data of ternary and quaternary composition spreads are
      approximated to locate catalysts of high activity within the search space. For
      quaternary systems, slice plots offer a good tool for visualization of the
      results. Using these approximation techniques, the composition of the most active
      catalysts can be predicted. The study documents that distinct relationships
      between chemical composition and catalytic function exist and can be described by
      mathematical models.

PMID- 16636843
TI  - Prevalence of temporomandibular disorder signs in patients with complete versus
      partial dentures.
AB  - OBJECTIVES: To determine the prevalence of signs of a temporomandibular disorder
      (TMD) in completely edentulous patients wearing upper and lower complete dentures
      (CD) and to compare this to the prevalence of signs in partially edentulous
      patients wearing upper and lower clasp-retained acrylic removable partial
      dentures (RPD). MATERIALS AND METHODS: A questionnaire and a clinical examination
      were used to assess 200 patients. One hundred of these were complete denture
      wearers being treated for the provision of replacement CD. The other 100 patients
      were partially edentulous patients, who had RPD replacing upper and lower
      partially missing teeth and their supporting structures. RESULTS: It was shown
      that there was a statistically significant difference between the two groups
      regarding the presence of temporomandibular signs. Partially edentulous patients
      wearing upper and lower RPD had a significantly higher prevalence of TMD signs
      than edentulous patients wearing CD (36% compared to 17%). They also exhibited
      significantly (P<0.04) more signs of joint tenderness (18%) on clinical
      examination compared to (5%) only in the CD-wearing patients. Tenderness upon
      palpation in the periauricular region was the most common site reported in both
      groups. CONCLUSIONS: The partially edentulous patients (wearing RPD) exhibited
      more TMD signs when compared with the CD-wearing patients. Significantly, more
      partially edentulous patients had joint tenderness (P<0.04) than did CD-wearing
      patients. The masseter muscle most commonly demonstrated muscle tenderness.

PMID- 16636845
TI  - Role of chagasin-like inhibitors as endogenous regulators of cysteine proteases
      in parasitic protozoa.

PMID- 16636846
TI  - The occurrence of Toxocara malaysiensis in cats in China, confirmed by sequence
      based analyses of ribosomal DNA.
AB  - Non-isotopic polymerase chain reaction (PCR)-based single-strand conformation
      polymorphism and sequence analyses of the second internal transcribed spacer (ITS
      2) of nuclear ribosomal DNA (rDNA) were utilized to genetically characterise
      ascaridoids from dogs and cats from China by comparison with those from other
      countries. The study showed that Toxocara canis, Toxocara cati, and Toxascaris
      leonina from China were genetically the same as those from other geographical
      origins. Specimens from cats from Guangzhou, China, which were morphologically
      consistent with Toxocara malaysiensis, were the same genetically as those from
      Malaysia, with the exception of a polymorphism in the ITS-2 but no unequivocal
      sequence difference. This is the first report of T. malaysiensis in cats outside
      of Malaysia (from where it was originally described), supporting the proposal
      that this species has a broader geographical distribution. The molecular approach
      employed provides a powerful tool for elucidating the biology, epidemiology, and
      zoonotic significance of T. malaysiensis.

PMID- 16636850
TI  - Mediastinal rhabdomyoma: case report and review of the literature.
AB  - Rhabdomyomas are benign tumors in which at least some cells are differentiated as
      skeletal muscle cells with cytoplasmic cross-striations. Extracardiac adult
      rhabdomyoma is an extremely uncommon benign neoplasm that usually involves the
      head and neck region. Rare cases have been reported to involve other sites of the
      body including mediastinum. We report the fourth case of mediastinal adult
      rhabdomyoma.

PMID- 16636847
TI  - Schistosomiasis--a century searching for chemotherapeutic drugs.
AB  - Schistosomiasis affects 200 million individuals in underdeveloped and developing
      regions and is a growing concern for travelers worldwide. There has been evidence
      of resistance to the praziquantel-based therapy and reports of acute-disease
      manifestation; therefore, other drugs affecting different stages of the
      schistosome parasites life cycle and alternative therapeutic regimens should be
      developed and become accessible. The present review results from a comprehensive
      search in the scientific literature for substances and compounds tested in the
      past centennial for schistosomiasis therapy. We gathered over 40 drugs providing
      information on therapeutic action in humans or animal model, toxicity,
      susceptible Schistosoma stages, species, etc. The drugs were grouped according to
      their known metabolic effects on the parasite, whether they are on membrane
      structure and function, carbohydrate metabolism, protein synthesis and function,
      or on nucleic acid metabolism. We discuss the current knowledge of drug-target
      interactions, their mechanism of action and possible therapy combinations.
      Furthermore, based in the literature and in our own experience with large-scale
      Schistosoma mansoni genome and transcriptome analyses, we put forward several
      recently described gene products that are promising target candidates for
      existing or new drugs.

PMID- 16636851
TI  - Incidental in vivo detection of an isolated hemangioma of the aortic valve in a
      man with a history of renal transplantation.
AB  - Hemangiomas of the cardiac valves are exceptional. To our knowledge, only ten
      cases of valve hemangiomas, six in the mitral and four in the tricuspid valve,
      have been reported in the English literature. We describe an incidentally
      detected aortic valve hemangioma of a 62-year-old man with chronic, degenerative
      aortic valve stenosis, who underwent renal transplantation 7 years before. We
      believe that this is the first report of a hemangioma in this localization and
      the first one in association with solid organ transplantation. The review of the
      literature of the adult cases of valve hemangioma, including this report,
      revealed that the average age was 47.2 years (range, 24 to 68 years). No clear
      sex predominance has been noted. Patients can be asymptomatic or experience
      sudden death. Symptomatic patients have complaints of palpitations, dyspnea, or
      syncopal episodes. Histologically, these valve tumors are classified as
      capillary, cavernous, and mixed. Mean tumor size is 1.1 cm (range, 0.6 to 2 cm).
      In 50% of cases the hemangioma is an incidental finding at autopsy or in a
      removed valve. Valve aortic hemangioma, despite its rarity, should be considered
      in the differential diagnosis of vascular lesions of this cardiac valve.

PMID- 16636856
TI  - Long-term strength training for community-dwelling people over 75: impact on
      muscle function, functional ability and life style.
AB  - The objective was to determine the impact of a 1-year mixed strength-training
      programme on muscle function, functional ability, physical activity and life
      style. Twice-a-week hospital-based exercise classes and a once-a-week home
      session were conducted. Nineteen healthy community-dwelling training (T) men
      (76.6 +/- 3.1 years), 19 women (77.5 +/- 4.0 years) and 20 matched controls (C)
      participated in this study. Training was given with a two multi-gym machines for
      the lower limbs (Sitting calf and Leg press, TECHNOGYM, Italy) at 60% of the
      repetition maximum (1 RM) and at home it was with elastic bands. The following
      were the measurements made: muscle function-maximum isometric strength of the
      knee extensors (KE) and ankle plantar flexors (PF) measured with a Cybex Norm
      dynamometer, leg extensor power (LEP) with the Nottingham Power Rig; functional
      abilities-functional reach, chair rise, bed rise, 6-min walking test, stair
      climbing, get up and go, one-leg standing; physical activity-aerobic activities
      over 3 MET intensity (AA3), intensity classes; life-style-mean daily energy
      expenditure (MDEE). Significant gains in muscle function and functional abilities
      in both training females and males were observed, but females improved
      significantly more than males. Males (T + C) showed higher AA3 times than females
      (T + C) (P = 0.02), with females significantly more involved in light-intensity
      activities. We observed a 60% increase (t = 2.45) in AA3 time in T, but no
      increase in C. Trained males increased Class 2 physical activity time by 146% (t
      = 2.82) and trained females by 16% (t = 2.23). MDEE increased by 10% (t=2.62) in
      trained males. Our long-term mixed programme can improve muscle function and
      functional abilities in elderly females and functional abilities in males. It can
      positively affect the amount of habitual physical activity and the life-style of
      males and females over 75.

PMID- 16636857
TI  - Acute resistance exercise does not change the hormonal response to sublingual
      androstenediol intake.
AB  - Sublingual intake of 21.4 mg androstenediol increases serum testosterone
      concentrations whereas swallowing 200 mg androstenediol does not. The duration of
      increase in serum testosterone following sublingual androstenediol (SL-DIOL) is
      unknown. Resistance exercise (EX) following SL-DIOL may cause larger increases in
      serum estradiol concentrations than while at rest. This project evaluated the
      duration of change in, and the effects of acute EX on, the hormonal response to
      SL-DIOL. Six young resistance trained males consumed either placebo (PL) or SL
      DIOL before a single session of EX or no exercise (Rest) in a random, double
      blind, crossover manner (for a total of four trials). Blood samples were
      collected before supplementation, and at 60, 120, 180, 240, 480, and 720 min post
      supplementation, with the exercise occurring between 60 and 120 min. The serum
      [total testosterone] increased (P < 0.05) at 60 min similarly in SL-DIOL-EX and
      SL-DIOL-Rest by approximately 115%, and at 120 min by approximately 107% with no
      differences due to exercise. The serum [estradiol] increased (P < 0.05) similarly
      in SL-DIOL-EX and SL-DIOL-Rest by approximately 33% at 60 min and approximately
      45% at 120 min, with no differences due to exercise. Serum [testosterone]
      returned to baseline by 240 min and serum [estradiol] returned to baseline by 720
      min post-intake. These findings indicate that SL-DIOL acutely elevates serum
      testosterone and estradiol concentrations, that EX does not alter the endocrine
      response to SL-DIOL, and that the increases in serum estradiol last between 480
      and 720 min while the increases in serum testosterone last <240 min following
      acute SL-DIOL intake.

PMID- 16636861
TI  - Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset:
      in vivo and in silico studies.
AB  - Assessment of the rate of muscle oxygen consumption, UO(2m), in vivo during
      exercise involving a large muscle mass is critical for investigating mechanisms
      regulating energy metabolism at exercise onset. While UO(2m) is technically
      difficult to obtain under these circumstances, pulmonary oxygen uptake, VO(2p),
      can be readily measured and used as a proxy to UO(2m). However, the quantitative
      relationship between VO(2p) and UO(2m) during the nonsteady phase of exercise in
      humans, needs to be established. A computational model of oxygen transport and
      utilization--based on dynamic mass balances in blood and tissue cells--was
      applied to quantify the dynamic relationship between model-simulated UO(2m) and
      measured VO(2p) during moderate (M), heavy (H), and very heavy (V) intensity
      exercise. In seven human subjects, VO(2p) and muscle oxygen saturation, StO(2m),
      were measured with indirect calorimetry and near infrared spectroscopy (NIRS),
      respectively. The dynamic responses of VO(2p) and StO(2m) at each intensity were
      in agreement with previously published data. The response time of muscle oxygen
      consumption, tauUO(2m) estimated by direct comparison between model results and
      measurements of StO(2m) was significantly faster (P < 0.001) than that of
      pulmonary oxygen uptake, tauVO(2p) (M: 13 +/- 4 vs. 65 +/- 7 s; H: 13 +/- 4 vs.
      100 +/- 24 s; V: 15 +/- 5 vs. 82 +/- 31 s). Thus, by taking into account the
      dynamics of oxygen stores in blood and tissue and determining muscle oxygen
      consumption from muscle oxygenation measurements, this study demonstrates a
      significant temporal dissociation between UO(2m) and VO(2p) at exercise onset.

PMID- 16636862
TI  - Seasonal training and heart rate and blood pressure variabilities in young
      swimmers.
AB  - To evaluate if changes in athletes' physical fitness due to seasonal training are
      associated with changes in cardiovascular autonomic control, nine swimmers (three
      males and six females; aged 14-18 years) were evaluated before and after 5 months
      of training and competitions. Maximal oxygen consumption (VO2max) and ventilatory
      threshold were determined during a maximal test; heart rate (HR) and blood
      pressure (BP) variabilities' power spectra were calculated at rest (supine and
      sitting positions) and in the recovery of two exercises at 25 and 80% pre
      training VO2max. At the end of the season: (a) VO2max and ventilatory threshold
      increased respectively by 12 and 34% (P<0.05); (b) at rest, HR decreased by 9 b
      min(-1) in both body positions, whereas BP decreased in supine position only by
      17%. No change in low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15
      1.5 Hz) normalized powers and in LF/HF ratio of HR variability and in LF power of
      systolic BP variability was observed. In contrast, a significant increase in HF
      alpha-index (about 12 ms mmHg(-1)) was found; (c) during recovery no change in
      any parameter was observed. Seasonal training improved exercise capacity and
      decreased resting cardiovascular parameters, but did not modify vagal and
      sympathetic spectral markers. The increase in alpha-index observed at rest after
      the season and expression of augmented baroreflex sensibility indicated however
      that HR vagal control could have been enhanced by seasonal training. These
      findings suggested that autonomic system might have played a role in short-term
      adaptation to training.

PMID- 16636863
TI  - Fatal impalement injury of the head due to a curtain rail.
AB  - During a dispute, a boy was injured by a curtain rail which penetrated the skull
      in the left frontal region and led to severe brain injury. Despite intensive
      medical care, death occurred 10 days later due to malignant cerebral edema. With
      regard to the question whether the trauma resulted from throwing or pushing, some
      biomechanical aspects are discussed including individual morphologic findings as
      well as the kinetic energy required for penetrating the skull. According to the
      calculated data, we conclude that the velocity necessary for penetrating could be
      reached by throwing the curtain rail.

PMID- 16636864
TI  - Postmortem distribution of 3,4-methylenedioxy-N,N-dimethyl-amphetamine (MDDM or
      MDDA) in a fatal MDMA overdose.
AB  - In this manuscript, a newly identified compound, 3,4-methylenedioxy-N,N
      dimethylamphetamine (MDDM or also called MDDA), was quantified. The substance was
      identified in the biological specimens of a 31-year-old man who died following a
      massive 3,4-methylenedioxymethamphetamine (MDMA) overdose. In addition, the
      postmortem distribution of the identified substance in various body fluids and
      tissues was evaluated. For MDDM quantitation, a formerly reported and validated
      liquid chromatography tandem mass spectrometry (LC-MS/MS) method was adapted. The
      following quantitative results of the MDDM quantitation were obtained: Femoral
      blood, aorta ascendens, and right atrial blood contained 2.5, 21.7, and 11.6 ng
      MDDM/ml, respectively. In left and right pleural fluid and pericardial fluid,
      concentrations of 47.0, 21.7, and 31.9 ng/ml, respectively, were found. MDDM
      levels in urine, bile, and stomach contents were 42.4, 1,101, and 1,113 ng/ml,
      respectively. MDDM concentrations in lungs, liver, kidney, and left cardiac
      muscle ranged from 12.8 to 39.8 ng/g, whereas these levels were below the limit
      of quantitation (< LOQ) in right cardiac and iliopsoas muscle. In conclusion, for
      the first time, MDDM was unambiguously identified in a fatal MDMA overdose. MDDM
      was probably present as a synthesis by-product or impurity in the MDMA tablets,
      which were taken in a huge amount by the victim, or MDDM was ingested separately
      and prior to the MDMA overdose. A third option, i.e., the eventual formation of
      MDDM as a result of postmortem methylation of MDMA by formaldehyde, produced by
      putrefaction processes or during storage under frozen conditions, is also
      discussed. The MDDM levels, substantiated in various body fluids and tissues, are
      in line with the distribution established for other amphetamine derivatives and
      confirm that peripheral blood sampling, such as that of femoral blood, remains
      the "golden standard".

PMID- 16636865
TI  - Effects of rounding errors on postmortem temperature measurements caused by
      thermometer resolution.
AB  - Beginning 7 h after death, a datalogger was used to measure the temperature in
      the external auditory canal of an adult male body placed in a refrigerated room.
      The sequence of measured values approximated a single exponential function with a
      correlation coefficient of 0.998475. This suggests that the starting time of body
      cooling in the refrigerated room under constant temperature can be calculated
      with less error using any two data points recorded by the datalogger. However,
      the results of such calculations varied widely and longer postmortem intervals
      demonstrated greater calculation errors. Periodic errors also appeared.
      Mathematical simulations showed that this variation was caused by rounding
      errors, which represent the difference between the thermometer readings and the
      true temperature. The resolution of the thermometer was 0.1 degrees C, a normal
      specification; however, even this led to noticeable rounding errors. Therefore,
      significant errors may influence postmortem interval estimations using other body
      temperatures. When body temperatures are used to determine the time of death, a
      method that minimizes rounding errors should be considered.

PMID- 16636866
TI  - [Hematogenous contact dermatitis after intravesicular instillation of mitomycin
      C].
AB  - Mitomycin C is an alkylating chemotherapeutic agent which is instilled
      intravesically to prevent recurrence of superficial bladder carcinomas. After
      several cycles of mitomycin C, our patient developed a pruritic genital
      dermatitis and palmar desquamation. Following exclusion of a fungal infection, we
      performed patch tests using the standard series, the major basic ointment
      ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%;
      the resulting diagnosis was allergic contact dermatitis due to delayed-type
      hypersensitivity to mitomycin C. The skin rash rapidly resolved with application
      of topical steroids, and the intravesical chemotherapy was changed to
      doxorubicin. Eczematous skin reactions are quite common side effects after
      intravesical instillation of mitomycin C. In the majority of cases, they are
      caused by delayed-type hypersensitivity reactions, presumably elicited by
      hematogenous spread of the allergen, and not by irritation. The sensitization
      most likely occurs via the bladder mucosa. In order to differentiate between
      allergic and toxic contact dermatitis, patch tests with the above-mentioned
      mitomycin C concentrations are useful. In cases of mild allergic contact
      dermatitis the intravesical chemotherapy might be continued with concomitant
      topical steroids.

PMID- 16636867
TI  - [Erythema annulare centrifugum Darier. Successful therapy with topical calcitriol
      and 311 nm-ultraviolet B narrow band phototherapy].
AB  - Erythema annulare centrifugum is an acute dermatosis of unclear etiology, which
      presents with annular erythematous lesions with marginal scale. Therapeutically,
      systemic and topical glucocorticosteroids are used primarily. We treated a
      patient with large lesions in the area of the thighs resistant to a therapy with
      topical glucocorticosteroids, with topical calcitriol in combination with 311 nm
      ultraviolet B narrow band phototherapy. After four weeks of treatment the skin
      lesions had cleared nearly completely without any side effects. The combination
      topical vitamin D3-analogue calcitriol and 311 nm ultraviolet B narrow band
      phototherapy was effective and can be regarded as a useful alternative to
      glucocorticosteroids for erythema annulare centrifugum.

PMID- 16636868
TI  - On the functional interaction between nicotinic acetylcholine receptor and Na+,K+
      ATPase.
AB  - Previous studies have shown that nanomolar acetylcholine (ACh) produces a 2 to 4
      mV hyperpolarization of skeletal muscle fibers putatively due to Na(+),K(+)
      ATPase activation. The present study elucidates the involvement of the nicotinic
      ACh receptor (nAChR) and of Na(+),K(+)-ATPase isoform(s) in ACh-induced
      hyperpolarization of rat diaphragm muscle fibers. A variety of ligands of
      specific binding sites of nAChR and Na(+),K(+)-ATPase were used. Dose-response
      curves for ouabain, a specific Na(+),K(+)-ATPase inhibitor, were obtained to
      ascertain which Na(+),K(+)-ATPase isoform(s) is involved. The ACh dose-response
      relationship for the hyperpolarization was also determined. The functional
      relationship between these two proteins was also studied in a less complex
      system, a membrane preparation from Torpedo electric organ. The possibility of a
      direct ACh effect on Na(+),K(+)-ATPase was studied in purified lamb kidney
      Na(+),K(+)-ATPase and in rat red blood cells, systems where no nAChR is present.
      The results indicate that binding of nAChR agonists to their specific sites
      results in modulation of ouabain-sensitive (most probably alpha2) isoform of
      Na(+),K(+)-ATPase, leading to muscle membrane hyperpolarization. In the Torpedo
      preparation, ouabain modulates dansyl-C6-choline binding to nAChR, and vice
      versa. These results provide the first evidence of a functional interaction
      between nAChR and Na(+),K(+)-ATPase. Possible interaction mechanisms are
      discussed.

PMID- 16636869
TI  - Results of instrumented posterolateral fusion in failed back surgery.
AB  - The success rate following revision surgery for failed back surgery is inherently
      low. However, a general consensus for a satisfactory surgical intervention after
      failed disc surgery has not yet been reached. We present a cohort study of 25
      adult cases treated by instrumented posterolateral fusion with or without nerve
      root exploration/decompression for recurrence or persistence of symptoms after
      previous disc surgery. The average age at surgery was 47 years (range 39-56
      years). Complications were seen in four patients in the form of intraoperative
      dural tears. A satisfactory clinical outcome was seen in 80% of the patients, and
      the overall fusion rate was 93%.

PMID- 16636870
TI  - Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral
      endothelin receptor antagonist.
AB  - OBJECTIVE: The purpose of this study was to investigate in healthy male subjects
      the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of
      clazosentan, an intravenous endothelin receptor antagonist. METHODS: Clazosentan
      was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12
      h. Each dose was given to a separate group of subjects, six of whom received
      clazosentan and two placebo. Vital signs, ECG, adverse events, and clinical
      laboratory variables were monitored to assess tolerability. Blood and urine
      samples were collected frequently for pharmacokinetic and pharmacodynamic
      determinations. RESULTS: Infusion of clazosentan up to doses of 30 mg/h for 3 h
      was well tolerated. A dose of 60 mg/h and longer infusions were less well
      tolerated and three subjects did not complete the 12-h infusion of 30 mg/h due to
      adverse events. Headache was the most commonly reported adverse event followed by
      nausea, vomiting, and nasal congestion. The pharmacokinetics of clazosentan were
      dose proportional in the dose range investigated. Values (mean and 95% confidence
      intervals) for clearance and volume of distribution at a dose of 10 mg/h for 3 h
      were 42.2 (36.6, 48.7) l/h and 32.4 (27.0, 38.8) l, respectively. Both variables
      were independent of dose. The elimination of clazosentan was characterized by a
      very rapid disposition phase with a half-life of 6-10 min. Compared to baseline,
      endothelin-1 concentrations increased approximately 2-fold after infusion of
      clazosentan but no dose-dependent relationship could be discerned for this
      effect. CONCLUSION: The observed tolerability, pharmacokinetic, and
      pharmacodynamic profile warrant further clinical development of clazosentan at
      lower doses.

PMID- 16636871
TI  - A juvenile-adult model with periodic vital rates.
AB  - A global branch of positive cycles is shown to exist for a general discrete time,
      juvenile-adult model with periodically varying coefficients. The branch
      bifurcates from the extinction state at a critical value of the mean, inherent
      fertility rate. In comparison to the autonomous system with the same mean
      fertility rate, the critical bifurcation value can either increase or decrease
      with the introduction of periodicities. Thus, periodic oscillations in vital
      parameter can be either advantageous or deleterious. A determining factor is the
      phase relationship among the oscillations in the inherent fertility and survival
      rates.

PMID- 16636880
TI  - The incidence, timing, and predisposing factors of germinal matrix and
      intraventricular hemorrhage (GMH/IVH) in preterm neonates.
AB  - BACKGROUND: Germinal matrix and intraventricular hemorrhage (GMH/IVH) is a known
      complication occurring in the first week of life in preterm neonates. However,
      the precise time of its occurrence and the ideal time to perform diagnostic
      imaging studies remain controversial. The purpose of this paper is to address
      these two issues in our patient population to allocate our resources to those at
      highest risk. MATERIALS AND METHODS: This study included 282 premature newborns
      (under 37 weeks of gestation) that were admitted to our neonate ICU in a year's
      time and screened for GMH/IVH. They were grouped in four categories according to
      their weight at birth, and according to their gestational age. All patients had a
      daily cranial ultrasound during the first week. It was then repeated once in the
      second week and once in the third. RESULTS: We found that the incidence of
      GMH/IVH among preterm neonates was 44.68%. It was inversely related to the weight
      and the age of the newborn. The onset of bleeding coordinated with the occurrence
      of hypoxia and respiratory distress requiring mechanical ventilation. The
      majorities occurred in the first 7 days of life; they were mostly grade I and II
      according to the Papule classification and silent for the most part.
      Complications were present in 41% of the survivors.

PMID- 16636881
TI  - Nutrition and hydration of patients in vegetative state: a statement of the
      Italian National Committee for Bioethics.

PMID- 16636888
TI  - Identification of the first archaeal oligopeptide-binding protein from the
      hyperthermophile Aeropyrum pernix.
AB  - The archaeon Aeropyrum pernix grows optimally at 90 degrees C and derives energy
      primarily from aerobic degradation of complex proteinaceous substrates. The
      ability of these nutrients to sustain growth is generally associated with the
      presence of oligopeptide transport systems, such as the well-known protein
      dependent ATP-binding cassette (ABC) transporters. This study is concerned with
      the isolation and characterisation of the first archaeal oligopeptide-binding
      protein (OppA(Ap)) from the extracellular medium of A. pernix. The protein shows
      a pI of 3.9 and a molecular mass of about 90 kDa under native conditions. By
      using a proteomic approach, the OppA(Ap)-encoding gene was identified (APE1583)
      and about 55% of the protein amino-acid sequence was validated. The extracellular
      purified protein was able to efficiently bind oligopeptide substrates such as
      Xenopsin. The amount of a liganded peptide to OppA(Ap) was about 70% at 90
      degrees C using a 1/100 (w/w) OppA(Ap)/substrate ratio. Sequence comparisons
      showed a weak but significant similarity of OppA(Ap) with bacterial oligopeptide
      binding proteins. Furthermore, APE1583 neighbouring genes encode for the cognate
      components of an ABC transport system, suggesting that these ORFs are organised
      in an operon-like structure, with OppA(Ap )as the extracellular component for the
      uptake of oligopeptides.

PMID- 16636889
TI  - Phytohormone levels in germinating seeds of Zea mays L. exposed to selenium and
      aflatoxines.
AB  - Seeds of Zea mays L. were exposed to aflatoxine B1 (AFB1), aflatoxine G1 (AFG1)
      and selenium (Se) alone and in combination and allowed to germinate. Phytohormone
      levels of GA-like substances (GAs), trans-Zeatin (t-Z) and Indole-3-acetic acid
      (IAA) were determined by High Performance Liquid Chromatography (HPLC) when the
      roots of the germinating seeds reach 1.5-3.0 cm in length. The levels of
      endogenous hormones decreased in seeds treated with AFB1 and AFG1 compared to
      control; however an increase was noted in seeds exposed to AFG1 and Se together.
      AFB1 and Se treatment caused reduced hormone levels in most of the treatments.
      When plants were exposed to Se alone, the highest levels of GAs, t-Z and IAA were
      observed in the application of 800 ppm Se. The highest levels of GAs, t-Z and IAA
      were observed when seeds were treated with 0.2 ppm AFG1 + 8 ppm Se, 0.2 ppm AFG1
      + 8 ppm Se and 0.2 ppm AFG1 + 0.08 ppm Se, respectively, whereas the lowest
      levels of the hormones were observed in 0.2 ppm AFB1 + 8 ppm Se, 0.2 ppm AFB1 +
      0.08 ppm Se and 0.1 ppm AFB1, respectively. In conclusion, the levels of
      phytohormones were reduced by the treatment of AFB1 and AFG1 alone. However Se
      removed the negative effect of AFB1 on phytohormones, but not AFB1.

PMID- 16636891
TI  - Condom use among South African adolescents: developing and testing theoretical
      models of intentions and behavior.
AB  - We developed and tested models of intentions and behavior among adolescents from
      Cape Town, South Africa. Data from 261 participants who completed an initial
      measure of attitudes, beliefs, and prior behavior were used to develop a model of
      intentions to use condoms based on the Theory of Planned Behavior (TPB) and
      additional constructs found to be important in previous research with
      adolescents. Of the initial sample, 227 (87%) completed a behavioral follow-up 4
      months later, and approximately one-third of those (n=72; 44 boys and 30 girls)
      reported having had sex in the prior 4 months. Data from this smaller sample were
      used to develop a model of condom use behavior based on intentions (as per the
      TPB) and the additional sub-population relevant constructs. Analyses generally
      supported the validity of the TPB in this context for predicting intentions and
      behavior. HIV knowledge and positive outlook (self-esteem and future optimism)
      were significantly related to TPB predictors of intentions. Intentions,
      acceptance of sexuality, and gender were significant predictors of behavior.
      Implications for the status of the TPB and the design of interventions for South
      African adolescents are discussed.

PMID- 16636892
TI  - The price of adherence: qualitative findings from HIV positive individuals
      purchasing fixed-dose combination generic HIV antiretroviral therapy in Kampala,
      Uganda.
AB  - Contrary to early expectations, recent studies have shown near-perfect adherence
      to HIV antiretrovirals in sub-Saharan Africa We conducted qualitative interviews
      with patients purchasing low-cost, generic antiretroviral therapy to better
      understand the social dynamics underlying these findings. We found that concerns
      for family well-being motivate adherence, yet, the financial sacrifices necessary
      to secure therapy may paradoxically undermine family welfare. We suggest that
      missed doses may be more due to a failure to access medication rather than a
      failure to adhere to medications, and that structural rather than behavioral
      interventions may be most useful to insure optimal treatment response.

PMID- 16636894
TI  - Prognostic impact of Skp2 and p27 in human breast cancer.
AB  - PURPOSE: The cell cycle is controlled by cyclin-dependent kinases and one of the
      key players is the cyclin-dependent kinase inhibitor p27. The F-box protein Skp2
      is a regulator of G1-S transition and promotes specifically the ubiquitin
      mediated proteolysis of p27 via the proteasome pathway. In breast carcinomas,
      overexpression of Skp2 has been implicated in cell transformation and
      oncogenesis, but no data are available on the association of Skp2 and p27. The
      purpose was to evaluate the prevalence of Skp2 and p27 expression and determine
      whether a combined index has prognostic power in breast carcinomas. EXPERIMENTAL
      DESIGN: Three hundred and thirty-eight breast cancer specimens were analyzed for
      Skp2 and p27 expression by immunohistochemistry. Results were compared with
      classical histopathological criteria as well as other prognostic markers (ER, PR,
      HER2, p53, Ki-67) and correlated with the clinical outcome. RESULTS: Thirty-four
      percent of breast cancers analyzed showed both a high expression for Skp2 and a
      low expression for p27. In univariate Kaplan-Meier analysis, this combination was
      found to be significantly associated with a worse clinical course (p<0.0001).
      Including staging, grading and the other tested marker, the Skp2/p27 index proved
      to be of prognostic relevance in multivariate analysis. CONCLUSIONS: The combined
      assessment of Skp2 and p27 identifies aggressive breast cancer. In long-term
      follow-up, high Skp2 and low p27 indicate an unfavorable course. Beyond the
      prognostic importance of the Skp2/p27 index, it could serve as a predictive
      marker for new molecular targeted therapies aiming at Skp2.

PMID- 16636895
TI  - Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative,
      highly proliferative breast carcinoma subtype.
AB  - Members of the syndecan and glypican families of cell surface heparan sulfate
      proteoglycans (HSPGs) are modulators of growth factor signaling and cell
      adhesion. Both loss and gain in expression of syndecans and glypicans has been
      associated with malignant progression. The goal of this project was to
      investigate a possible relationship between expression of cell surface HSPGs
      (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or
      clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast
      carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1,
      syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone
      receptor (PR). Clinical follow-up information was available for up to 18.6 years
      (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma
      cells ranged from complete loss to high expression, but glypican-1 was detected
      only in a small subset of breast carcinomas. Expression of all three HSPGs was
      significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025;
      syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression
      correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1
      expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS:
      p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify
      syndecan-1 as an independent prognostic marker, which was due to its significant
      association with established prognostic factors. The strong association between
      cell surface HSPGs and the Ki67 proliferation marker would support a biologic
      role in carcinoma growth regulation. Furthermore, the close correlation between
      syndecan expression and negative ER status raises the possibility of hormonal
      regulation or more likely an association with an aggressive, ER-negative
      carcinoma phenotype.

PMID- 16636897
TI  - Understanding and improving the validity of self-report of parenting.
AB  - Although researchers using parental self-report data have questioned its validity
      (Holden, 2001) and called for more work in this area (Krevans & Gibbs, 1996;
      Locke & Prinz, 2002), methodological concerns regarding self-report about
      parenting practices have not been addressed adequately. The susceptibility of
      parental report to systematic distortions suggests a need for research on ways to
      improve self-report. This paper attempts to synthesize research findings from
      other fields (e.g., survey methodology) about ways to improve the validity of
      self-report, and to discuss the implications for self-report of parenting
      behaviors. Methods for improving self-report are presented for each of the 5
      major tasks in responding to a question: (1) understanding the question, (2)
      recalling relevant behavior, (3) inference and estimation, (4) mapping the answer
      onto the response format, and (5) "editing" the answer for reasons of social
      desirability. Self-administered interviewing, audio-computer-assisted
      interviewing, pretesting, conversational interviewing, and the decompositional
      item may be among the best candidates for use in parental self-report.
      Recommendations are offered with respect to strategies that might prove useful in
      improving parental assessment of parenting, and to research efforts to evaluate
      the utility and potential costs of these strategies.

PMID- 16636898
TI  - Pharmacological profile of the "triple" monoamine neurotransmitter uptake
      inhibitor, DOV 102,677.
AB  - 1. The molecular and behavioral pharmacology of DOV 102,677 is characterized. 2.
      This characterization was performed using radioligand binding and
      neurotransmitter uptake assays targeting the monoamine neurotransmitter
      receptors. In addition, the effects of DOV 102,677 on extracellular
      neurotransmitter levels were investigated using in vivo microdialysis. Finally,
      the effects of DOV 102,677 in the forced swim test, locomotor function, and
      response to prepulse inhibition was investigated.3. DOV 102,677 is a novel,
      "triple" uptake inhibitor that suppresses [(3)H]dopamine (DA),
      [(3)H]norepinephrine (NE) and [(3)H]serotonin (5-HT) uptake by recombinant human
      transporters with IC(50) values of 129, 103 and 133 nM, respectively. Radioligand
      binding to the dopamine (DAT), norepinephrine (NET), and serotonin (SERT)
      transporters is inhibited with k (i) values of 222, 1030, and 740 nM,
      respectively. DOV 102,677 (20 mg/kg IP) increased extracellular levels of DA and
      5-HT in the prefrontal cortex to 320 and 280% above baseline 100 min after
      administration. DA levels were stably increased for the duration (240 min) of the
      study, but serotonin levels declined to baseline by 200 min after administration.
      NE levels increased linearly to a maximum of 348% at 240 min post-dosing.
      Consistent with these increases in NE levels, the density of beta-adrenoceptors
      was selectively decreased in the cortex of rats treated with DOV 102,677 (20
      mg/kg per day, PO, 35 days). 4. DOV 102,677 dose-dependently reduced the amount
      of time spent immobile by rats in the forced swim test, a model predictive of
      antidepressant activity, with a minimum effective dose (MED) of 20 mg/kg and a
      maximal efficacy comparable to imipramine. This decrease in immobility time did
      not appear to result from increased motor activity. Further, DOV 102,677 was as
      effective as methylphenidate in reducing the amplitude of the startle response in
      juvenile mice, without notably altering motor activity. 5. In summary, DOV
      102,677 is an orally active, "balanced" inhibitor of DAT, NET and SERT with
      therapeutic versatility in treating neuropsychiatric disorders beyond depression.

PMID- 16636899
TI  - Mechanisms of the Anti-Ischemic Effect of Angiotensin II AT( 1 ) Receptor
      Antagonists in the Brain.
AB  - 1. Circulating and locally formed Angiotensin II regulates the cerebral
      circulation through stimulation of AT(1) receptors located in cerebrovascular
      endothelial cells and in brain centers controlling cerebrovascular flow. 2. The
      cerebrovascular autoregulation is designed to maintain a constant blood flow to
      the brain, by vasodilatation when blood pressure decreases and vasoconstriction
      when blood pressure increases. 3. During hypertension, there is a shift in the
      cerebrovascular autoregulation to the right, in the direction of higher blood
      pressures, as a consequence of decreased cerebrovascular compliance resulting
      from vasoconstriction and pathological growth. In hypertension, when perfusion
      pressure decreases as a consequence of blockade of a cerebral artery, reduced
      cerebrovascular compliance results in more frequent and more severe strokes with
      a larger area of injured tissue. 4. There is a cerebrovascular angiotensinergic
      overdrive in genetically hypertensive rats, manifested as an increased expression
      of cerebrovascular AT(1) receptors and increased activity of the brain
      Angiotensin II system. Excess AT(1) receptor stimulation is a main factor in the
      cerebrovascular pathological growth and decreased compliance, the alteration of
      the cerebrovascular eNOS/iNOS ratio, and in the inflammatory reaction
      characteristic of cerebral blood vessels in genetic hypertension. All these
      factors increase vulnerability to brain ischemia and stroke. 5. Sustained
      blockade of AT(1) receptors with peripheral and centrally active AT(1) receptor
      antagonists (ARBs) reverses the cerebrovascular pathological growth and
      inflammation, increases cerebrovascular compliance, restores the eNOS/iNOS ratio
      and decreases cerebrovascular inflammation. These effects result in a reduction
      of the vulnerability to brain ischemia, revealed, when an experimental stroke is
      produced, in protection of the blood flow in the zone of penumbra and substantial
      reduction in neuronal injury. 6. The protection against ischemia resulting is
      related to inhibition of the Renin-Angiotensin System and not directly related to
      the decrease in blood pressure produced by these compounds. A similar decrease in
      blood pressure as a result of the administration of beta-adrenergic receptor and
      calcium channel blockers does not protect from brain ischemia. 7. In addition,
      sustained AT(1) receptor inhibition enhances AT(2) receptor expression,
      associated with increased eNOS activity and NO formation followed by enhanced
      vasodilatation. Direct AT(1) inhibition and indirect AT(2) receptor stimulation
      are associated factors normalizing cerebrovascular compliance, reducing
      cerebrovascular inflammation and decreasing the vulnerability to brain
      ischemia.8. These results strongly suggest that inhibition of AT(1) receptors
      should be considered as a preventive therapeutic measure to protect the brain
      from ischemia, and as a possible novel therapy of inflammatory conditions of the
      brain.

PMID- 16636900
TI  - Cytidine and uridine increase striatal CDP-choline levels without decreasing
      acetylcholine synthesis or release.
AB  - AIMS: Treatments that increase acetylcholine release from brain slices decrease
      the synthesis of phosphatidylcholine by, and its levels in, the slices. We
      examined whether adding cytidine or uridine to the slice medium, which increases
      the utilization of choline to form phospholipids, also decreases acetylcholine
      levels and release. METHODS: We incubated rat brain slices with or without
      cytidine or uridine (both 25-400 microM), and with or without choline (20-40
      microM), and measured the spontaneous and potassium-evoked release of
      acetylcholine. RESULTS: Striatal slices stimulated for 2 h released 2650+/-365
      pmol of acetylcholine per mg protein when incubated without choline, or 4600+/
      450 pmol/mg protein acetylcholine when incubated with choline (20 microM). Adding
      cytidine or uridine (both 25-400 microM) to the media failed to affect
      acetylcholine release whether or not choline was also added, even though the
      pyrimidines (400 microM) did enhance choline;s utilization to form CDP-choline by
      89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine
      release from hippocampal and cortical slices. Cytidine or uridine also failed to
      affect acetylcholine levels in striatal slices, nor choline transport into
      striatal synaptosomes. CONCLUSION: These data show that cytidine and uridine can
      stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis
      or release.

PMID- 16636902
TI  - An examination of sociocultural factors associated with health and health care
      seeking among Latina immigrants.
AB  - The purpose of this study was to examine the sociocultural factors associated
      with health maintenance and health care seeking among Latina immigrants. Data
      were collected from eight focus groups with 54 Latina immigrants between the ages
      of 19 and 62 (M=29.3+/-9.34). The PEN-3 model provided the framework for the
      study. Most of the participants came from Mexico; 46% had not completed high
      school; 85.2% had been in the United States for less than 7 years, and 73.6%
      reported not having health insurance coverage. Participants identified both
      positive and negative perceptions, enablers, and nurturers associated with health
      maintenance and health care seeking. Participants acknowledged the importance of
      physical, mental, and spiritual health and what they should do to be healthy.
      Despite such knowledge, they tended to engage in unhealthy behaviors due to a
      variety of nonstructural barriers such as lack of time, "tradition," and
      procrastination. They tended to use alternative/complementary medicine first, and
      then seek medical help if these practices are not effective. Many women believe
      that they do not have control over their own health attributing this lack of
      control to the "system." Participants also mentioned structural barriers to
      seeking health care such as lack of transportation, lack of proper documentation,
      lack of health insurance, language barriers, long waiting time at the clinics,
      and lack of knowledge on where to go for affordable care. Our study suggests that
      there are important structural and nonstructural barriers that hinder health
      maintenance and care seeking. The findings also lend support to the PEN-3 model,
      and suggest that positive perceptions, enablers, and nurturers associated with
      health maintenance and health care seeking, if properly reinforced, can
      counterbalance negative perceptions, enablers and nurturers in this population.

PMID- 16636903
TI  - The developmental behavior genetics of drug involvement: overview and comments.
AB  - The papers in this special issue have in common an interest in developmental
      variations in the heritability of substance use, abuse, and problems. A number of
      the studies are longitudinal, and even those that are cross-sectional are
      analytically focused on whether heritability, shared, and nonshared
      environmentality effects are constant or change over the period from onset of use
      to the time when problem use is more constant. This commentary provides an
      overview of the work from a developmental psychopathology perspective. Findings
      are linked to the existing longitudinal/developmental literature on the
      epigenesis of substance use disorders and similarities and contradictions are
      noted. Suggestions for next step work, involving the need for increased
      differentiation of the substance abuse phenotypes, the utilization of phenotypic
      measures that delineate heterogeneity of course, and more precise definition of
      the specific environmental variations that underlie shared and nonshared
      environmental liability, are provided.

PMID- 16636905
TI  - Availability of services for women in outpatient substance abuse treatment: 1995
      2000.
AB  - Women entering substance abuse treatment have more severe substance abuse
      problems and more medical and psychiatric comorbidities than men. Research shows
      that specialized women's services are associated with better retention and
      outcomes but relatively little is known about their availability nationwide. This
      study examined the adoption and implementation of reproductive and female
      sensitive social services in a national sample of outpatient substance abuse
      treatment (OSAT) organizations in 1995 (N = 617) and 2000 (N = 571) by several
      organizational factors. Overall, reproductive and social services for women have
      not been widely adopted, although some services did increase over the study
      period, particularly social services. There was no evidence of large-scale
      decreases in service availability over the study period, although child care did
      decline. Nonprofit and public ownership (relative to for-profit) were associated
      with greater service provision. Managed care units had greater service adoption
      compared to nonmanaged care units, and this increased over time. Public units and
      hospital-affiliated units had greater service implementation than other units.
      However, OSAT units did not always implement the services they adopted,
      suggesting access to some services may be restricted.

PMID- 16636906
TI  - A survey of programs for parents with mental illness and their families:
      Identifying common elements to build the evidence base.
AB  - Little is known about the effectiveness of interventions for families living with
      parental mental illness. Existing interventions offer information about
      successfully implemented treatments, which may demonstrate effectiveness in
      research. In the current study, directors of programs for parents with mental
      illness and their families were interviewed. Qualitative analyses revealed
      noteworthy similarities with respect to target population; funding; community
      context; agency context; mission, theoretical orientation, and assumptions; locus
      of care and essential services; desired outcomes; and moderators. Program
      similarities were identified to provide parameters for research, and to
      contribute to the development of testable hypotheses. Family-centered, strengths
      based approaches were identified across program directors as critical to
      intervention success.

PMID- 16636907
TI  - The effect of a medicaid managed care program on patterns of psychiatric
      readmission among adolescents: evidence from Maryland.
AB  - This study evaluates the effect of Maryland's Medicaid managed care program on
      patterns of psychiatric readmission for adolescents. Rates and frequency of
      readmissions are compared before (FY 1997) and after (FY 1998) the implementation
      of Maryland's Medicaid managed care program. Medicaid claims files were reviewed
      for 881 adolescents consecutively admitted to three major Maryland psychiatric
      hospitals between July 1, 1996 and June 30, 1998. Adolescents admitted after the
      managed care reforms were more likely to experience multiple readmissions. The 1
      year cumulative rate of readmission pre- and postmanaged care was 33% and 38%,
      respectively; the highest risk period fell within the first 15-30 days
      postdischarge. The high rate of early readmissions raises concern about the
      quality of care and the adequacy of community-based services. Findings also
      suggest that youths with serious emotional disturbances who are high users of
      inpatient care may be adversely affected by the managed care reforms.

PMID- 16636908
TI  - Measuring strategies used by mental health providers to encourage medication
      adherence.
AB  - Mental health clinicians rely on a range of legal mandates and interpersonal
      strategies of encouragement and pressure to address nonadherence to treatment.
      This paper describes the development and testing of a scale to assess formal and
      informal strategies used by clinicians to encourage adherence to medication. The
      16-item measure was administered to 271 clinicians and analyzed using Rasch
      measurement modeling. Subsequently, items were revised and readministered to a
      second sample of 44 clinicians in an urban mental health clinic. Rasch analysis
      of the items yielded a coherent and internally consistent unidimensional measure
      of strategies used to promote adherence that vary on a continuum of pressure or
      social control. Criterion-related validity was assessed by observing the
      association of the measure with clinician ratings of client adherence. The
      resulting measure may be employed in future studies to examine the ways in which
      clinician behavior relates to medication adherence and to consumer perceptions of
      treatment alliance, quality of care, and perceived coercion.

PMID- 16636909
TI  - A prospective examination of high-cost health services utilization among drug
      using prisoners reentering the community.
AB  - The use of health services by prisoners during their incarceration and after
      their return to the community impacts the U.S. health care system and health care
      costs associated with this system. These health care costs are expected to
      increase over the next decade as more prisoners return to their communities. The
      current study prospectively examines the use of high-cost health care services
      emergency room visits and hospitalizations-among 565 male drug-abusing prisoners
      about 1 year after prison release. A series of structural equation models were
      used to examine predisposing factors, including health status and drug use, and
      to estimate the frequency of high-cost health service utilization. As expected,
      health status was the most robust predictor of high-cost health services.
      However, the finding that drug abuse had nonsignificant relationships with high
      cost health services utilization was not expected. Discussion focuses on health
      care service issues and health problems as prisoners' transition from prison to
      the community.

PMID- 16636910
TI  - Through a mother's eyes: Sources of bias when mothers with co-occurring disorders
      assess their children.
AB  - Mothers are the principal informants on children's emotional and behavioral
      functioning. Maternal assessments of child functioning can be influenced by a
      mother's own psychological state. The magnitude and valence of distortion in
      maternal assessments associated with current maternal mental health and substance
      abuse symptoms were explored in a clinical sample of 253 mothers with co
      occurring disorders and histories of trauma. Analyses estimated the correlation
      between current maternal symptoms and child assessments after controlling for
      maternal history of disorders, child's history of service utilization for
      emotional and behavioral problems, and demographic characteristics. Current
      maternal psychological distress was associated with more pessimistic assessments
      on the problem-focused Child Behavior Checklist, whereas current maternal
      substance abuse problems were associated with more optimistic assessments on both
      problem-focused and strength-based measures. Clinicians and researchers may
      choose to take distortion into account when treatment plans or measures of change
      are based on maternal assessments.

PMID- 16636911
TI  - Pediatric telepsychiatry in ontario: Caregiver and service provider perspectives.
AB  - Families in rural areas face significant geographic and economic obstacles to
      obtaining pediatric mental health services. Telepsychiatry promises the
      possibility of extending specialized expertise into areas that have no resident
      psychiatrists. In this study, user perspectives and experiences of a pediatric
      telepsychiatry program serving rural communities in Ontario, Canada, were
      explored. Qualitative, exploratory methods were utilized because of the complex
      nature of mental health services needs and provision in rural communities. Focus
      groups with rural mental health service providers and interviews with family
      caregivers of children receiving a telepsychiatry consultation were conducted.
      The purpose of this research was to evaluate the benefits and limitations of
      providing pediatric psychiatric services via video-technology to inform future
      program development and health policy. Whereas participants in the study
      indicated that their experiences with the telepsychiatry service had been
      positive, the need for additional local services to support treatment
      recommendations was emphasized.

PMID- 16636912
TI  - Integration of oral health care and mental health services: Dental hygienists'
      readiness and capacity for secondary prevention of eating disorders.
AB  - Often the first to observe overt health effects of eating disorders, dentists and
      dental hygienists play a fundamental role in the secondary prevention of eating
      disorders. The purpose of this study was to explore readiness and capacity for
      integration of oral health and mental health services. Employing a randomized
      cross-sectional study based upon the Transtheoretical and Health Belief Models,
      data were collected from 378 dental hygienists. Results reveal that the majority
      do not currently engage in secondary prevention practices. Only 18% of
      respondents indicated referring patients exhibiting oral manifestations of eating
      disorders to treatment. Significantly increasing the likelihood of assessment,
      referral, and case management included modifying factors regarding greater
      perceived self-efficacy, and knowledge of oral cues of disordered eating, as well
      as the individual's perception pertaining to severity of eating disorders.
      Implications for bridging dental care to mental health services include
      increasing behavioral capacity among dental hygienists via consciousness raising
      and improved self-efficacy.

PMID- 16636913
TI  - Regulation of osteoblast gene expression and phenotype by polylactide-fatty acid
      surfaces.
AB  - Cell function is influenced by surface structure and molecules. Molecules that
      enhance cellular differentiation can be applied to tissue scaffold surfaces to
      stimulate endogenous tissue regeneration. The application of this approach to
      bone implants yields surfaces coated with factors (proteins, peptides, etc...)
      that promote the differentiation of osteoblasts, the cells that make bone.
      Increased bone formation leads to increased healing and union of the implant with
      endogenous bone. To obtain better control over surface coating we developed PLLA
      copolymers with allyl (PLLA-co-DAG) and 3-hydroxypropyl (PLLA-co-HP) side chains
      to which we can attach functional groups. Given the potential of fatty acids
      being able to incorporate into lipid bilayers and/or influence gene expression,
      we grafted different fatty acid side chains to PLLA-co-HP by esterifying the
      corresponding fatty acids with the PLLA-co-HP 3-hydroxypropyl side chains. The
      effects of the polymer modifications on osteoblasts were then evaluated. While
      cellular morphology differed between surface coatings, they did not reflect
      changes in cellular phenotype. Changes in gene expression were most evident with
      arachidonate and 3-hydroxypropyl side-chains which exhibited osteoblast
      differentiating capabilities. Linoleate, myristate, oleate, and stearate ester
      side-chains did not have a significant influence on osteoblast phenotype. Growth
      characteristics of osteoblasts did not differ between the fatty acid copolymer
      films, although cells grown on PLLA-co-HP exhibited a trend toward increased
      growth. Taken together our findings demonstrate that surface fatty acid
      composition can impact osteoblast phenotype.

PMID- 16636914
TI  - Parkin modulates gene expression in control and ceramide-treated PC12 cells.
AB  - Mutations in the parkin gene cause autosomal-recessive early-onset parkinsonism
      as a result of the degeneration of mesencephalic dopaminergic neurons. In cell
      culture models, parkin expression has been shown to protect against cell death
      mediated by the sphingolipid ceramide. To determine whether the antiapoptotic
      effect of parkin involves changes in gene expression, we used Affymetrix
      oligonucleotide microarrays to analyse gene expression in stably transfected PC12
      cells which conditionally overexpress parkin, that were treated or not with C2
      ceramide. Overexpression of parkin and ceramide treatment both modulated gene
      expression. A number of the genes upregulated in the presence of ceramide, and
      modulated by parkin, were associated with apoptosis or cellular stress reactions.
      We validated the upregulation of four such genes (CHK, EIF4EBP1, GADD45A and PTPN
      5) by real-time PCR after 3, 6, 9 and 12 h of ceramide treatment in cells that
      overexpressed parkin or not. All were upregulated 2 to 11-fold, 3 and 6 h after
      application of ceramide. Parkin overexpression reduced the upregulation of
      EIF4EBP1, GADD45A and PTPN-5, but only at 6 h. These results suggest that, in
      this assay, the cytoprotective effect of parkin might result not only from its E3
      ligase activity, but also from direct or indirect modulation of gene expression
      in a time-dependent manner.

PMID- 16636915
TI  - Mammalian Pol III promoter H1 can transcribe shRNA inducing RNAi in chicken
      cells.
AB  - Double-stranded RNA-mediated interference (RNAi) has recently emerged as a
      powerful reverse genetic tool to silence gene expression in multiple organisms.
      RNAi based on DNA vector is not sufficiently established in chicken species. The
      present study was performed to evaluate RNAi induced by shRNA transcribed from
      mammalian Pol III promoter H1 in the chicken cells by using a dual fluorescence
      reporter assay, a plasmid encoding GFP and a plasmid encoding RFP. The evaluation
      of RNAi efficiency was performed in two kinds of chicken cell type: primary CEF
      cells and chicken DT-40 cells by lipofection. GFP- and RFP-expressing cells were
      observed under fluorescent microscopy, and their mRNAs content were analyzed by
      quantitative RT-PCR. The intensity of the green fluorescence generated by GFP was
      greatly suppressed by human H1 promoter transcribed GFP-shRNA. Quantitative RT
      PCR analysis showed that normalized GFP mRNA expression was reduced to 37 and 32
      in primary CEF and DT-40 cells, respectively. In contrast to GFP, the intensity
      of the red fluorescence generated by RFP protein and the RFP mRNA levels remained
      unchanged. Consequently, it was concluded that the RNAi induced by shRNA
      transcribed from mammalian Pol III promoter H1 is applicable to suppress the gene
      expression specifically and efficiently in chicken cells.

PMID- 16636916
TI  - shRNA transcribed by RNA Pol II promoter induce RNA interference in mammalian
      cell.
AB  - RNA interference is a powerful tool for gene functional analysis in mammals.
      Permanent gene suppression can be achieved by siRNAs as stem-loop precursors
      transcribed from RNA Pol III promoter such as H1 and U6 based on vector. This
      approach, however, has a major limitation: inhibition can not be controlled in a
      time or tissue specific manner because the RNA Pol III promoter is not time or
      tissue specific. To overcome these limitations, we designed a strategy that
      allows synthesis of small hairpin RNAs in a GFP-fused form mediated by RNA Pol II
      promoter CMV to efficiently and specifically knock down expression of both
      exogenous and endogenous genes in mammalian cells. As assayed by both
      fluorescence observing and quantitative RT-PCR, the protein and mRNA products of
      exogenous gene RFP were efficiently and specifically inhibited; quantitative RT
      PCR and western blotting results respectively demonstrated that endogenous lamin
      B2 mRNA and protein was suppressed without global down-regulation of protein
      synthesis. Furthermore, GFP-fused shRNA efficacy for RNAi is dependent on target
      position based on this vector system. This method may provide a novel approach
      for the application of RNAi technology in suppressing gene expression in
      mammalian system.

PMID- 16636917
TI  - Identification and characterization of the human SCAN domain zinc-finger gene
      ZNF449.
AB  - Zinc-finger proteins play important roles in various cellular functions,
      including cell proliferation, differentiation, and apoptosis. In this study, we
      identified a gene encoding a zinc finger protein named ZNF449, which was isolated
      from human testis cDNA library and mapped to Xq26.3 by searching the UCSC genomic
      database. The ZNF449 cDNA consists of 4035 nucleotides and has a 518-amino acids
      open reading frame. The predicted protein contains a leucine-rich region (LER or
      SCAN domain) at the N-terminus. At the C-terminus of the protein, there are 7
      C(2)H(2) (Cys2-His2) zinc-finger motifs. The expression pattern of ZNF449 showed
      that it was ubiquitously expressed in 18 human adult tissues. ZNF449 protein was
      located in the nucleus when overexpressed in cultured cells. These results
      indicate that ZNF449 is a member of the zinc-finger family and it may function as
      a transcription factor.

PMID- 16636918
TI  - Semi-anaerobic growth conditions are favoured by some Escherichia coli strains
      during heterologous expression of some archaeal proteins.
AB  - Host cell physiology is known to play a crucial role in the expression of foreign
      genes in heterologous systems. Expression of archaeal genes in anaerobic or semi
      anaerobic growth conditions of E. coli has been previously reported to be a means
      of improving solubility of some proteins. Here, we report that some of the
      Rosetta strains of E. coli, which harbour the rare tRNA genes for the expression
      of archaeal genes, favour semi-anaerobic conditions for the expression of
      putative FMN binding domain of glutamate synthase from Methanocaldococcus
      jannaschii at low inducer concentrations.

PMID- 16636919
TI  - Isolation of sperm vesicles from adult male mayflies and other insects to prepare
      high molecular weight genomic DNA samples.
AB  - We describe here a simple and efficient protocol for genomic DNA isolation from
      adult males of insects: e.g., Ephemeroptera, Odonata, Orthoptera and Dictyoptera.
      To minimize contamination of external DNA source, the sperm vesicles were
      isolated from male individuals from which high molecular weight genomic DNA was
      extracted. According to this protocol, the genomic DNA samples obtained were high
      quality (intact), and abundant enough for genotyping analyses and molecular
      cloning. The protocol reported here enables us to process a huge number of
      individuals at a time with escaping from cross-contamination, and thus it is
      quite useful for conducting genetic studies at least in some species of insects.
      The large yield of high molecular weight DNA from single individual may be
      advantageous for non PCR-based experiments. As a case study of the protocol,
      partial coding sequences of histone H3 and EF-1alpha genes are determined for
      some insects with PCR-amplified DNA fragments.

PMID- 16636920
TI  - DNA bending in the replication zone of the C3 DNA puff amplicon of Rhynchosciara
      americana (Diptera: Sciaridae).
AB  - Intrinsic bent DNA sites were identified in the 4289 bp segment encompassing the
      replication zone which directs DNA amplification and transcription of the C3-22
      gene of Rhynchosciara americana. Restriction fragments showed reduced
      electrophoretic mobility in polyacrylamide gels. The 2D modeling of the 3D DNA
      path and the ENDS ratio values obtained from the dinucleotide wedge model of
      Trifonov revealed the presence of four major bent sites, positioned at
      nucleotides -6753, -5433, -5133 and -4757. Sequence analysis showed that these
      bends are composed of 2-6 bp dA.dT tracts in phase with the DNA helical repeat.
      The circular permutation analysis permitted the verification that the fragments
      containing the bending sites promote curvature in other sequence contexts.
      Computer analyses of the 4289 bp sequence revealed low helical stability (DeltaG
      values), negative roll angles indicating a narrow minor groove and a putative
      matrix attachment region. The data presented in this paper add to information
      about the structural features involved in this amplified segment.

PMID- 16636921
TI  - Further study on the esterase patterns of sibling species in the Drosophila
      saltans subgroup (saltans group): intraspecific and interspecific variations in
      the development.
AB  - Twenty of the 32 esterase bands previously detected in the adults of D.
      prosaltans, D. saltans and D. austrosaltans were found in larvae and pupae
      studied in this work. The results showed that, in addition to expressing the
      highest number of esterase bands, the adult stage of the three species exhibited
      the highest degree of expression (amount of synthesis) for most of the bands.
      Differences between larval and pupal stages were detected in the degree of
      expression (amount of synthesis) of the bands and in the frequency of samples
      expressing them. The frequencies of expression of the bands corresponding to
      genes in loci 1-3 were greater in pupae than in larvae while the frequencies of
      expression of the bands corresponding to genes in loci 4-9 were predominantly
      expressed in larvae or were equal in both developmental stages. Like the adults,
      larvae, pupae and empty pupal cases (which were also studied in this work) showed
      specific esterases. Taken together, the observations showed that, in the species
      studied, every developmental stage is characterized by specific bands and by
      specific frequency and degree of expression of the bands shared with other
      stages.

PMID- 16636922
TI  - The effects of temperature shock on transcription and replication in
      Rhynchosciara americana (Diptera: Sciaridae).
AB  - The chromosomal response to temperature shock in Rhynchosciara americana is
      similar to that observed in other Diptera. After a 33 degrees C/90 min or a 36
      degrees C/30 min shock the reaction for RNA polymerase II (RpII) is enhanced at
      five loci. The most prominent of these was identified by in situ hybridization as
      the site of the hsp70 gene. At 33 degrees C, an accumulation of heat shock factor
      (HSF) and an increase in the level of RpII was observed at some heat shock loci
      after 5 min and reached a maximum after 15 min at most loci. The pattern of
      accumulation of HSF and RpII at individual heat shock loci was similar and their
      increases were generally coordinated among the loci. RpII gradually decreased at
      sites active prior to shock, the rate of decrease varying with the site. The B2
      DNA puff retained RpII for a significant length of time while the histone locus
      still contained RpII after a shock of 90 min. With a 36 degrees C/30 min shock,
      the size of the heat shock puffs and the intensities of HSF and RpII peaked at 1
      4 h post stress. The level of HSF declined rapidly after 1 h while the level of
      RpII remained high for an additional 4 h. The reaction of the DNA puffs to heat
      shock varied. Usually they did not regress completely and retained traces of
      RpII. BrdU incorporation continued at both amplifying and non-amplifying bands
      after shock but on average it appeared depressed for about 24 h post stress.

PMID- 16636923
TI  - Karyotype and chromosomal location of 18S-28S and 5S ribosomal DNA in the
      scallops Pecten maximus and Mimachlamys varia (Bivalvia: Pectinidae).
AB  - This work describes the karyotype and chromosomal location of the ribosomal DNA
      (rDNA) of Pecten maximus and Mimachlamys varia, two commercial scallop species
      from Europe. According to the chromosome centromeric index values found, the
      karyotype of P. maximus is composed of 1 metacentric, 2 metacentric
      submetacentric, 1 telocentric-subtelocentric and 15 telocentric pairs, and that
      of M. varia of 4 metacentric, 2 subtelocentric-submetacentric, 9 subtelocentric,
      3 subtelocentric-telocentric and 1 telocentric-subtelocentric pairs. In P.
      maximus, 18S-28S rDNA was located by FISH on a metacentric-submetacentric pair,
      and in M. varia on a subtelocentric-submetacentric pair using both silver
      staining and FISH. PCR amplification of the 5S rDNA unit yielded a single product
      of about 460 bp (P. maximus) and 450 bp (M. varia), that used as probe revealed a
      5S rDNA site on a telocentric pair in P. maximus and a subtelocentric pair in M.
      varia. Two-color FISH or sequential silver staining of 5S rDNA-FISH-metaphases
      corroborated that the two gene families are located on different chromosomes in
      both species. A comparative analysis of the data allowed the inference of
      karyotypic relationships within scallops.

PMID- 16636924
TI  - Ovis aries POU1F1 gene: cloning, characterization and polymorphism analysis.
AB  - POU1F1 (PIT-1/GHF-1) is a transcription factor with critical role in the
      transcriptional regulation of multiple genes in the pituitary and also important
      for the survival, differentiation and proliferation of three pituitary cell
      types. To understand the regulation of POU1F1 gene in Ovis aries we report its
      cloning, sequencing and characterization. The sequenced 5787 bp included six
      exons and two complete introns. Ovine POU1F1 gene has a high level of
      conservation with its bovine, human and rat counterparts showing 98.2%, 91.2% and
      86.2% of similarity at the coding level, respectively. All six exons were
      analyzed for polymorphism detection in 100 animals of the Portuguese indigenous
      ovine breed 'Churra da Terra Quente'. One polymorphism was found at codon 58 in
      exon 2, in one allele of 4 animals leading to a change from cysteine to tyrosine
      (2% allelic frequency). In exon 3 two polymorphisms were detected: a G to A
      transition altering a glycine to an asparagine at codon 89 in one allele of one
      animal (0.5% allelic frequency) and another G to A transition at codon 105
      converting an alanine into a threonine in one allele of 3 animals (1.5% allelic
      frequency). These polymorphisms might change the structure of the POU1F1 protein
      and modify gene-expression. In intron 4, an A to G transition was detected in one
      allele of six animals (3% allelic frequency). Exons 1, 4 and 6 showed no
      polymorphisms.

PMID- 16636925
TI  - Mating system in a low-density natural population of the dioecious wind
      pollinated Patagonian cypress.
AB  - The mating system of a species is an essential factor that determines the
      genotypic frequencies of its populations in each generation. Thus, knowledge in
      this regard is important in the application of practical measures in conservation
      and forest tree breeding. Austrocedrus chilensis (D.DON) PIC. SER. ET BIZZARRI:
      is a member of the Cupressaceae native to the Andean-Patagonian Forest of
      Argentina and Chile with regional economic importance. It is a dioecious tree
      with pollen and seeds distributed by wind. Isozyme markers were utilized to study
      the mating system of this species through the survey of individual effective
      pollen clouds in a natural low-density population. If random mating occurs,
      effective pollen clouds that pollinate single seed trees are expected to be
      genetically homogeneous. The classical HardyWeinberg test of panmixia was also
      performed. Although it failed to reject random mating, the analysis of the pollen
      clouds showed that this mating pattern does not occur. Evidence of locally
      distributed heterogeneous pollen clouds is presented. The two methods are
      critically compared.

PMID- 16636926
TI  - Evolutionary consequences of dispersal ability in cactus-feeding insects.
AB  - Although gene flow is an important determinant of evolutionary change, the role
      of ecological factors such as specialization in determining migration and gene
      flow has rarely been explored empirically. To examine the consequences of
      dispersal ability and habitat patchiness on gene flow, migration rates were
      compared in three cactophagous longhorn beetles using coalescent analyses of
      mtDNA sequences. Analyses of covariance were used to identify the roles of
      dispersal ability and habitat distribution in determining migration patterns.
      Dispersal ability was a highly significant predictor of gene flow (p< 0.001), and
      was more important than any other factor. These findings predict that dispersal
      ability may be an import factor shaping both microevolutionary and
      macroevolutionary patterns; this prediction is borne out by comparisons of
      species diversity in cactus-feeding groups.

PMID- 16636927
TI  - Polymorphic chromosomal specificity of centromere satellite families in
      Arabidopsis halleri ssp. gemmifera.
AB  - The chromosomal localizations of repetitive DNA clusters (ribosomal DNA and
      centromere satellites) were analyzed by fluorescent in situ hybridization in five
      strains of Arabidopsis halleri ssp. gemmifera. All five A. gemmifera strains have
      three chromosome pairs with 45S (5.8S-16S-26S) rDNA loci, and one pair with both
      5S and 45S rDNA loci. These localizations are different from that of A. thaliana.
      Very unusually, there are three families of centromeric satellite DNAs (pAa,
      pAge1, and pAge2), and they showed polymorphism among the five strains studied.
      Overall, we found four different centromere satellite compositions. A plant from
      Fumuro was heterozygous for the chromosome specificities of centromere satellite
      families, possibly due to a reciprocal translocation involving centromere
      regions. Changes of centromeric satellite repeats appear to be rapid and frequent
      events in the history of A. gemmifera, and seem to occur by exchanging clusters
      as units.

PMID- 16636928
TI  - Temporal changes in the inequality of early growth of Cunninghamia lanceolata
      (Lamb.) Hook.: a novel application of the Gini coefficient and Lorenz asymmetry.
AB  - Growth within tree populations varies among individuals due to changes in biotic
      and abiotic factors. The degree of such variation, defined as growth inequality,
      serves as a useful indicator of the uniformity of growth within a population in
      response to the prevalent environmental conditions. By application of the Gini
      coefficient (G), an index for inequality, we characterized the early growth
      inequality of ninety crosses of Chinese fir (Cunninghamia lanceolata (Lamb.)
      Hook.) and their open-pollinated parental lines. Tree cumulative height was
      measured annually for 8 consecutive years. Both the crosses and parental lines
      exhibited temporal changes in growth inequality. The inequality of total height
      among the crosses decreased logarithmically with age by nearly 3-fold after 13
      growing seasons, suggesting that tree height became less variable among the
      crosses as trees grew larger. Interestingly, the Lorenz asymmetry, an index
      reflecting the shape of the Lorenze curve from which G is derived, revealed that
      the inequality of annual height increment among the crosses resulted from an
      alternate contribution of the fast-growing and slow-growing trees. Among parental
      lines, two provenances with the smallest and the largest overall inequality in
      total height showed a similar pattern of changes in annual growth inequality, and
      the provenance differences were consistent over time. Compared to the other
      provinces, a local provenance exhibited less variation in total height among
      individual trees as reflected by a smaller value of inequality, and was better
      adapted to the field conditions. Our results demonstrated the sensitivity and
      usefulness of the Gini coefficient and Lorenz asymmetry for the analysis of
      growth inequality in non-natural populations. Growth inequality is a potentially
      useful evaluation criterion for early selection. Given comparable initial growth,
      provenances/families with lower growth inequality values would likely outperform
      those with higher growth inequality, and eventually tree size of the latter would
      be more variable due to greater variations among individual trees. Assessment of
      growth inequality at early ages will advance our understanding of variability of
      tree growth within a population, facilitate forest genetics improvement programs,
      and enhance the efficiency of tree breeding.

PMID- 16636929
TI  - Diversity of boll weevil populations in South America: a phylogeographic
      approach.
AB  - A phylogeographic approach was conducted to assess the geographic structure and
      genetic variation in populations of the boll weevil Anthonomus grandis, which is
      the most harmful insect pest of cotton in the Americas. COI and COII
      mitochondrial gene sequences were analyzed to test a former hypothesis on the
      origin of the boll weevil in Argentina, Brazil and Paraguay, using samples from
      Mexico and USA as putative source populations. The analysis of variability
      suggests that populations from South American cotton fields and nearby disturbed
      areas form a phylogroup with a central haplotype herein called A, which is the
      most common and widespread in USA and South America. The population from Texas
      has the A haplotype as the most frequent and gathers in the same group as the
      South American populations associated with cotton. The sample from Tecoman
      (Mexico) shows high values of within-nucleotide divergence, shares no haplotype
      in common with the South American samples, and forms a phylogroup separated by
      several mutational steps. The sample from Iguazu National Park (Misiones
      Province, Argentina) has similar characteristics, with highly divergent
      haplotypes forming a phylogroup closer to the samples from cotton fields, than to
      the Mexican group. We propose that in South America there are: populations with
      characteristics of recent invaders, which would be remnants of "bottlenecks" that
      occurred after single or multiple colonization events, probably from the United
      States, and ancient populations associated with native forests, partially
      isolated by events of historical fragmentation.

PMID- 16636930
TI  - Gene finding on the Y: fruitful strategy in Drosophila does not deliver in
      Anopheles.
AB  - The Anopheles gambiae genome project yielded almost complete sequences for the
      autosomes and for a large part of the X chromosome, however, no information for
      the Y chromosome was obtained. Yet, by design, fragmented Y chromosome sequences
      should be present in the resulting assembly. Here we report the search for
      Anopheles Y chromosome genes using a strategy successfully applied for
      identification of Y genes in Drosophila. A complete set of the unmapped scaffolds
      was targeted in a broad TBLASTN search using both A. gambiae predicted genes and
      all proteins from nr database as query sequences. After filtering of the BLAST
      report, we selected 181 scaffolds possibly containing fragments of Y chromosome
      genes to experimentally test their Y-linkage. Surprisingly, none of the tested
      sequences appeared to originate from the Y chromosome. Several factors could
      account for the failure to detect Y genes, including their different organization
      in A. gambiae compared to Drosophila and the suboptimal quality of the assembly
      and annotation of the Anopheles genome. Regardless of the cause, our results
      illuminate problems associated with the genome analysis of outbred organisms.

PMID- 16636934
TI  - T-889C IL-1alpha promoter polymorphism influences the response to oral
      cyclophosphamide in scleroderma patients with alveolitis.
AB  - Cyclophosphamide (CYC) is the cornerstone of the treatment of systemic sclerosis
      (SSc)-associated fibrosing alveolitis (FAS). Despite treatment with CYC, in a not
      negligible proportion of SSc-FAS patients, deterioration in lung function can be
      observed. Interleukin-1 (IL-1) cluster gene single nucleotide polymorphisms
      (SNPs) were implicated in the pathogenesis of some interstitial lung diseases and
      may favor the progression of restrictive lung disease in SSc. The present
      retrospective case-control study was conducted on 18 SSc patients previously
      treated with oral CYC (2 mg/kg) and medium-dose steroids (prednisone 25 mg for 3
      months and then tapered to 5 mg/day) for the presence of FAS-defined as the
      presence of areas of ground-glass attenuation on high-resolution computed
      tomography (HRCT) and a recent deterioration in lung function. The T/C
      substitution at position -889 of the IL-1alpha promoter gene (T-889C) was
      determined by polymerase chain reaction and restriction length fragment analysis.
      Patients carrying the T allele showed a significant decrease in forced vital
      capacity (FVC) values after 12 months of therapy (2.46+/-1.09 vs 2.59+/-1.17 l),
      while wild-type patients showed an increase in FVC values (2.73+/-0.54 vs 2.54+/
      0.5 l) (p=0.005 between the two groups, analysis of variance for repeated
      measures). Patients with the T-889C polymorphism presented higher baseline
      erythrocyte sedimentation rates (ESR) compared to wild-type patients (50.3+/-25.4
      vs 23.3+/-17.7 mm/h). Baseline ESR inversely correlated with the variation of FVC
      (DeltaFVC) after 12 months of therapy (r=-0.50 and p<0.05). The two groups were
      otherwise similar with respect to autoantibodies, age, disease duration, disease
      subset, radiological HRCT grade, and baseline lung physiology. The T-889C
      polymorphism represents a marker for worse functional responses to CYC in SSc
      FAS. The mechanisms by which this SNP may negatively influence the response to
      CYC therapy are unknown, but might be linked to increased inflammatory responses
      in the lungs.

PMID- 16636935
TI  - The frequency of hypermobility and its relationship with clinical findings of
      fibromyalgia patients.
AB  - The etiology and pathogenic mechanisms of fibromyalgia (FM) are unknown. A number
      of studies have suggested that there was a link between hypermobility and FM. In
      this study, we aimed to expose the frequency of hypermobility in FM patients and
      its relation with clinical findings. For this reason, 236 women (118 FM women as
      study group and 118 healthy women as control group) were enrolled in the study.
      Joint hypermobility was evaluated in the participants by using Beighton scoring
      system. The rate of joint hypermobility among FM patients (Beighton score of at
      least 4 or more) was found to be higher than the control group (46.6 vs 28.8%).
      This result was also statistically meaningful (p<0.05). In addition, the mean
      Beighton score of FM group was observed to be higher than the control (3.68 vs
      2.55, p<0.001). Although not reaching statistical difference (p>0.05), more
      severe clinical findings were observed in FM patients with hypermobility when
      compared with ones without.

PMID- 16636936
TI  - The natural course of progressive systemic sclerosis patients with interstitial
      lung involvement.
AB  - OBJECTIVE: The aim of the study is to assess the natural course of systemic
      sclerosis (SSc) in patients with interstitial lung involvement and to evaluate
      the effects of treatment. MATERIALS AND METHODS: Sixty SSc patients with
      interstitial lung involvement were included in the study and history and
      retrospective data records of the patients were reviewed. RESULTS: It was
      observed that 47 patients (78.3%) had Raynaud's phenomenon, 7 patients (11.7%)
      had skin involvement, 5 patients (8.3%) had joint involvement, and 1 patient
      (1.7%) had gastrointestinal system involvement as the first manifestation of the
      disease. Lung involvement had developed on an average of 113 +/- 106 months after
      the first manifestation of the disease and was apparent within the first year in
      10 patients (16.7%), between 1 and 2 years in 3 patients (5%), between 2 and 3
      years in 2 patients (3.3%), between 3 and 4 years in 5 patients (8.3%), between 4
      and 10 years in 21 patients (35%), and after 10 years in 19 patients (31.7%).
      When the symptoms of lung involvement appeared, 37 patients (61.7%) were not
      receiving treatment while 23 (38.3%) were using an immunosuppressive agent. The
      time interval of lung involvement for the treated patients was 131 +/- 95 months
      while it was 101 +/- 112 months in untreated patients (p>0.05). CONCLUSION: In
      SSc patients with interstitial pulmonary involvement, the disease frequently
      starts with Raynaud's phenomenon and pulmonary symptoms tend to appear at a mean
      of 7 years after the onset of disease. The first sign of the disease, the
      probability of interstitial pulmonary involvement, is highest during the first 15
      years after. Although this probability decreases after 15 years, in up to 10% of
      the patients, interstitial pulmonary involvement can still occur even up to 40
      years. Immunosuppressive treatment is not effective in preventing the development
      of pulmonary involvement. However, it delays the manifestation of pulmonary
      symptoms for nearly 4 years.

PMID- 16636937
TI  - Low-dose methotrexate-induced pancytopenia.
AB  - Methotrexate (MTX) has gained wide acceptance among both patients and
      rheumatologists due to its efficacy and safe therapeutic window in a variety of
      inflammatory rheumatological disorders. However, it has the potential to cause
      serious, life-threatening complications and even mortality. In the present
      series, we have reviewed our data of five patients who developed serious
      pancytopenia after the use of MTX, including one who died. Two of these resulted
      from prescription errors by primary care physicians. The clinical, laboratory,
      and outcome profile of all five cases are discussed with a brief review of the
      literature about MTX-induced pancytopenia. There is an urgent need to increase
      awareness in primary care physicians, patients, and pharmacists toward informed
      prescribing, dispensing, and monitoring of MTX to prevent such mishaps in the
      future.

PMID- 16636938
TI  - The global perspective of osteoporosis : the ILAR lecture, June 2004, Berlin.

PMID- 16636939
TI  - 3-T MRI reveals cranial and thoracic inflammatory changes in giant cell
      arteritis.
AB  - Giant cell arteritis (GCA) is a diagnostic challenge. The correct diagnosis is
      needed for immediate initiation of corticosteroid treatment since blindness is a
      dreaded complication. Typically, the superficial cranial arteries are affected by
      this granulomatous vasculitis of large- and medium-sized arteries. However, GCA
      is not limited to the cranial arteries. Involvement of various arteries such as
      the cervical and thoracic arteries can also occur. Here, we report a case of
      histologically proven GCA with cranial and extracranial involvement. We
      illustrate the usefulness of a comprehensive vascular high-resolution magnetic
      resonance imaging examination that combines assessment of mural inflammatory
      changes of the small temporal and occipital arteries with the evaluation of
      extracranial vasculature to assist in the difficult non-invasive diagnosis and to
      determine the extent of this inflammatory disease.

PMID- 16636941
TI  - [The Times They Are A-Changin'].

PMID- 16636942
TI  - [Severe complications due to a dubious therapy].

PMID- 16636944
TI  - [Anaesthesia education at german university hospitals: the teachers' perspective 
      - results of a nationwide survey].
AB  - AIM OF THIS STUDY: The principle purpose of this study was to collect data on the
      conditions and practice of anaesthesia education as well as the teaching
      qualification of consultants at German university hospitals. Based upon the
      collected data, areas of weakness and strength as well as measures required to
      improve anaesthesia training are described. METHODS: A questionnaire containing
      26 items was mailed to 607 consultants employed at 41 German university hospitals
      in June 2003. RESULTS: A total of 255 questionnaires was analysed (response rate:
      43 %). Genuine training activities account for 14 % of the working hours of the
      participating consultants. On average, at the institutions of participating
      consultants, novices work for a duration of 1 month together with a consultant
      anaesthetist before they give anaesthetics without direct and constant
      supervision. When asked to describe the predominant method of training at their
      institution 71 % indicated "case-oriented teaching"; however, 53 % chose "see
      one, do one, teach one" and 49 % "learning by doing" as method of training as
      well (multiple choice). According to 63 % of respondents, departmental
      educational activities usually happen after their regular working hours. "Daily
      workload" (96 %), "time pressure" (96 %), "lack of time" (96 %) and "lack of
      personnel" (90 %) were indicated as the main obstacles of teaching. According to
      80 % of respondents, a dedicated financial budget for education does not exist;
      instead, financial resources of third parties (industry) (58 %), of the state
      (for research und undergraduate education) (60 %) and of patients service (66 %)
      are used to ensure training of anaesthesia residents. CONCLUSION: Due to a lack
      of a dedicated financial budget for resident training and an increasing economic
      pressure, "lack of time" and "lack of personnel" are the main factors leading to
      the situation at German university hospitals that consultants can only spend 14 %
      of their working hours for teaching purposes despite of sufficient qualification
      and motivation. As a consequence, novice anaesthetists are faced with the
      situation to be working without direct and constant supervision after 1 month of
      training.

PMID- 16636945
TI  - [Risks and complications of epidural neurolysis -- a review with case report].
AB  - Racz's minimal invasive epidural catheter procedure, also known as "epidural
      neuroplasty" is not only utilized in patients suffering from failed spine surgery
      ("failed back surgery syndrome") but also increasingly applied to non-surgical
      back pain patients to prevent chronification or deterioration. Its hypothesized
      principle of action is local epidural lysis of adhesions, neurolysis of vertebral
      nerve roots and local lavage of proinflammatory mediators by repeated injection
      of local anesthetics, corticosteroids, hyaluronidase and hypertonic saline
      solution. However adverse events are well known to occur in epidural neuroplasty.
      Complications of epidural neuroplasty are due to the procedure itself or due to
      specific drugs-related side effects. Unintended dural puncture, administration of
      the drugs to the subarachnoid or subdural space, catheter shearing, infection and
      severe hemodynamic instability during application are most commonly observed
      adverse events. Complications related to the procedure itself occur immediately,
      while complications relating to drug administration show later onset. Within this
      context, we report a case of severe meningitis with neurologic sequelae in a
      patient who received Racz catheter-treatment for unspecific low-back pain and
      provide an overview of the literature on other potential severe complications. As
      a consequence, we recommend that the Racz catheter procedure as yet should be
      restricted to controlled clinical trials with rigorous inclusion- and exclusion
      criteria.

PMID- 16636946
TI  - Use of the LMA-ProSeal in an experimental pig model -- a potential animal model
      for laryngeal mask airway research: results of a pilot study.
AB  - OBJECTIVE: In light of the increased use of the LMA-ProSeal (P-LMA) it seems
      desirable to consider the P-LMA for prolonged surgical cases or post-operative
      ventilation. Long-term use could carry the risk of serious complications. An
      experimental pig model could be used to gain basic knowledge about long-term use
      before conducting clinical trails. In this randomized controlled study we tested
      the hypothesis if prolonged positive pressure ventilation (PPV) with the P-LMA in
      the pig is possible. METHODS: The P-LMA was used for airway maintenance under
      general anaesthesia and PPV in 15 German country pigs. Randomised into 3 groups,
      the animals were ventilated for 90, 150 and 390 minutes, respectively. Arterial
      blood gas measurements were used to determine adequacy of ventilation. Airway
      leak pressure (P (leak)) and maximum tidal volume (TV) were measured in the
      supine, lateral and prone positions. A bronchoscopic examination was performed to
      detect signs of aspiration. RESULTS: Adequate ventilation was demonstrated both
      after 120 min (4.7 +/- 0.4 kPa) and 360 min (4.7 +/- 0.5 kPa). The corresponding
      PaO(2) at FiO(2) = 1.0 was 59 +/- 5 kPa and 64 +/- 10 kPa, respectively. The mean
      P (leak) was 34 +/- 7 cm H(2)O. Change of position did not result in any
      significant change in P(leak) or maximum TV kg (-1). There was no bronchoscopic
      evidence of aspiration in any pig. CONCLUSION: It was possible to ensure
      sufficient PPV with the P-LMA in the pig over different periods of time and in
      different body positions without any complications of airway management. The P
      LMA can be used for PPV in the pig for durations of up to 390 minutes. We
      conclude that investigations into the long-term use of the LMA can be carried out
      in a pig model.

PMID- 16636947
TI  - [Influence of neuromuscular blockade on the airway leak pressure of the ProSeal
      laryngeal mask airway].
AB  - BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is increasingly used for
      surgical procedures that might require the intraoperative use of neuromuscular
      blocking agents. The airway seal of the PLMA depends on the interplay of the
      surrounding soft tissue of the neck and the cuff of the mask. An intraoperative
      neuromuscular blockade could lead to a decrease of the airway leak pressure (P
      (leak)) secondary to the relaxation of the muscles of the neck. With this study
      we tested the hypothesis that a neuromuscular blockade can result in a decreased
      P (leak) of the PLMA. METHODS: The P (leak) of the PLMA was studied in 73 female
      patients under total intravenous anaesthesia with propofol (0.1 - 0.15 mg kg (-1)
      min (-1)) and remifentanil (0.1 - 0.3 microg kg (-1) min (-1)) before and after a
      complete neuromuscular blockade produced by intravenous injection of 0.6 mg kg (
      1) Rocuronium. RESULTS: The P (leak) decreased by more than 10 % of the baseline
      P (leak) in 8 out of 73 patients (11 %); however, in the entire study population
      there was no significant difference between the mean baseline P (leak) (28.5 +/-
      7.3 cm H(2)O) and the mean P (leak) after complete neuromuscular blockade (29.1
      +/- 7.0 cm H(2)O); (p = 0.128). CONCLUSION: No general correlation between
      application of a neuromuscular blocking agent and a decrease of the mean P (leak)
      was found. However, the decrease of the P (leak) by more than 10 % in 11 % of the
      patients shows that in certain patients the application of neuromuscular blocking
      agents can result in a decreased P (leak) of the PLMA and indicates the necessity
      to control the P (leak) of the PLMA under complete muscle paralysis
      preoperatively when neuromuscular blocking agents are used.

PMID- 16636948
TI  - [Respiratory sinus arrhythmia as predictor of blood pressure stability during
      anaesthetic induction in diabetics].
AB  - OBJECTIVE: Diabetics with cardiovascular autonomous neuropathy (CAN) can show
      severe hypotension during the course of anaesthesia. To improve the safety of
      anaesthesia, pre-operative evaluation of this concomitant disorder is
      recommended. The conventional test battery described by Ewing and Clarke to
      diagnose CAN is relatively time-consuming and complex. The aim of this study was
      to evaluate whether patients at risk could be reliably identified with less
      diagnostic effort. METHODS: Fifty patients with diabetes mellitus undergoing an
      ophthalmosurgical procedure were investigated. To evaluate their cardiovascular
      reflex status, the following tests were performed one day before surgery:
      determination of heart rate variation (HRV) under deep respiration (6
      breaths/min), and the response of heart rate (max/min 30:15 ratio) and blood
      pressure after getting up from a supine position. Anaesthesia was induced with
      thiopental and fentanyl and maintained with enflurane/N (2)0; vecuronium was
      administered for tracheal intubation. Patients whose systolic blood pressure fell
      below 90 mm Hg during the induction phase were assigned to Group H (hypotensive),
      the remaining patients to Group N (non-hypotensive). The groups were compared
      regarding the pre-operatively collected variables. RESULTS: The demographic data
      were comparable in the two groups with exception of the length of diabetes.
      Regarding blood pressure reaction during orthostatic load, there was no
      significant difference between the groups. In contrast, the parameters of HRV
      under deep respiration (with exception of the "mean circular resultant") and the
      max/min 30 : 15 ratio were significantly lower in patients of Group H than in
      Group N. The best differentiation between the groups offered the E/I ratio (=
      quotient resulting from the longest R-R interval during expiration (E) and the
      shortest R-R interval during inspiration (I) under deep breathing) as a measure
      of respiratory sinus arrhythmia. The incidence of hypotension during anaesthetic
      induction in patients with a normal E/I ratio was 8.7 %, but in patients with a
      pathologically reduced E/I ratio 51.9 % ( P = 0.0019). The sensitivity of this
      test concerning hypotension that occurred was 87.5 %, the specificity 61.7 %.
      CONCLUSION: The available results prove the close connection between the pre
      operatively measured breadth of respiratory sinus arrhythmia and blood pressure
      response during anaesthetic induction. Patients at risk of hypotension can be
      identified reliably and quickly during pre-operative screening with the help of a
      single, simple test procedure.

PMID- 16636949
TI  - ["Small-volume-resuscitation" in preclinical and clinical emergency].

PMID- 16636951
TI  - [Ultrasound in anesthesia -- a transient shadow or a new horizon for
      anaesthesists?].

PMID- 16636952
TI  - [History and development of sonography in anesthesiology].

PMID- 16636953
TI  - [Ultrasound guidance in regional anesthesia].

PMID- 16636954
TI  - [Ultrasound directed punctures in neuro-axial regional anesthesia].

PMID- 16636955
TI  - [Sonography in emergency medicine: only play or enhancement?].

PMID- 16636956
TI  - [Ultrasound and instruction in anesthesia].

PMID- 16636957
TI  - [Nerve stimulation based peripheral regional anesthesia: technique of the old
      fashioned or sonography-directed peripheral regional anesthesia a technique for
      ninnies?].

PMID- 16636958
TI  - [The use of ultrasound in intensive care medicine].

PMID- 16636959
TI  - [Economic aspects of ultrasound in anesthesia].

PMID- 16636960
TI  - [Removal of an epidural catheter under ongoing antithrombotic therapy].
AB  - A rare though extremely harmful complication in neuraxial anaesthesia is an
      epidural hematoma which can be associated with deleterious consequences for the
      patient, e. g. persistent paraplegia. The risk of epidural haematomas after
      neuraxial blockade is dependent on abnormal anatomy of the spine, difficult and
      multiple punctures and coagulation disorders. Especially when patients undergo
      therapy with anticoagulants like low molecular heparin or platelet inhibitors
      (tyclopidine) or a combination of them, the indication for neuraxial blockade
      must strictly outweigh risk of spinal bleeding. In this context, the precautions
      and contraindications are the same for spinal puncture and catheter insertion as
      for catheter removal. We describe the case of a patient who underwent emergency
      coronary angioplasty in combination with coronary stent implantation due to acute
      postoperative myocardial infarction following knee replacement in continuous
      epidural anaesthesia. Under the symptoms of a beginning local infection at the
      puncture site the epidural catheter had to be removed in spite of ongoing
      antithrombotic therapy. A possible management of such cases is discussed with
      regard to risk minimization.

PMID- 16636961
TI  - [Post-lobectomy bronchopleural fistula -- a challenge for postoperative intensive
      care].
AB  - Bronchopleural fistula (BPF) and bronchial stump insufficiency (BSI) after
      lobectomies and pneumonectomies are dreaded complications with incidences of up
      to 12 % and a mortality rate of up to 51 %. Apart from the basic illness causes
      include complications like aspiration-pneumonia and ARDS, formation of empyema as
      well as histories of sepsis. Corticoid treatments, old age, diabetes mellitus,
      previous irradiation as well as post-operative mechanical ventilation
      (barotrauma) are often counted among contributing causes. Suturing the bronchus
      and reinforcement by tissue are still the methods of choice, but they are often
      counter-indicated in high-risk patients. Endoscopic treatments with partial lung
      occlusions, e. g. by insertion of spongiosa, coils, and/or fibrin glue have been
      described. However, they require the respective area to be probable. With only
      one third the rate of success is quite unsatisfactory. The retro-graded
      instillation of inflammatory-selerotizing substances, like doxycycline, via a
      chest tube leads to a pleurodesis caused by adhesion of the remaining lung
      parenchyma to the thoracic wall and a reduction in size of the residual pleural
      space. In an 82-year old female patient a BPF of the second upper lobe bronchus
      was detected after a middle lobe resection for abscess and post-radiation ulcer
      following a mastectomy for carcinoma. The leakage was detected on bronchoscopy by
      retro-graded instillation via the chest tube of methylene-blue solution into the
      thoracic cavity. After administering the water-soluble contrast agent
      amidotrizoic acid in a similar manner a CT confirmed the diagnosis. As the
      bronchial segment concerned could not be entered selectively, preservation of the
      right lung lobe's residual ventilation by endoscopic-occlusion procedures was
      ruled out. Employing a strictly conservative therapy (spontaneous ventilation,
      retro-graded doxycycline instillations) complete healing with a fully ventilated
      lower lobe could be achieved over a period of 78 days. BPF as well as residual
      intro-thoracic cavities after lobectomies pose a serious problem. Using methylene
      blue for a retro-graded demonstration of BPF during bronchoscopy presents a
      feasible and cost-efficient diagnostic method. A strictly applied conservative
      therapy including short-time low-pressure artificial respiration as well as
      obliteration by fibrous tissue of the thoracic cavity using doxycycline is a
      feasible procedure for inoperable high-risk patients.

PMID- 16636964
TI  - 12-Acetoxyhawtriwaic acid lactone, a diterpene from Egletes viscosa, attenuates
      capsaicin-induced ear edema and hindpaw nociception in mice: possible mechanisms.
AB  - The diterpene, 12-acetoxyhawtriwaic acid lactone (AHAL, tanabalin) isolated from
      the flower buds of Egletes viscosa Less. (Asteraceae) was evaluated on capsaicin
      induced ear edema and hindpaw nociception in mice. AHAL (12.5, 25 and 50 mg/kg,
      P. O.) significantly attenuated the ear edema response to topically applied
      capsaicin (250 microg), in a dose-related manner. At similar doses, AHAL also
      suppressed the nocifensive paw-licking behavior induced by intraplantar injection
      of capsaicin (1.6 microg). These responses to capsaicin were also greatly
      inhibited by ruthenium red (3 mg/kg, S. C.), a non-competitive capsaicin receptor
      (TRPV1) antagonist. The anti-edema effect of AHAL (50 mg/kg) seems unrelated to
      either blockade of mast cell degranulation or to histamine and serotonin receptor
      antagonism since AHAL did not modify the paw edema response induced by
      intraplantar injections of compound 48/80, histamine or serotonin. However, the
      hindpaw edema induced by substance P and vascular permeability increase induced
      by intraperitoneal acetic acid were significantly suppressed by AHAL. The
      antinociceptive effect of AHAL (50 mg/kg) was unaffected by naloxone pretreatment
      but was significantly antagonized by theophylline and glibenclamide, the
      respective blockers of adenosine and K(ATP)-channels. AHAL (50 mg/kg, P. O.) did
      not impair the ambulation or motor coordination of mice in open-field and rota
      rod tests. These data suggest that AHAL inhibits acute neurogenic inflammation
      possibly involving capsaicin-sensitive TRPV1-receptors, endogenous adenosine and
      ATP-sensitive potassium channels.

PMID- 16636965
TI  - N-acetylphenylisoserinates of Lactarius sesquiterpenoid alcohols--cytotoxic,
      antiviral, antiproliferative and immunotropic activities in vitro.
AB  - In the present study a new group of derivatives of both paclitaxel and Lactarius
      sesquiterpenes, the N-acetylphenylisoserinates of Lactarius sesquiterpenoid
      alcohols, was tested for antiviral, cytotoxic, antiproliferative and immunotropic
      activities in vitro. Among the 13 compounds tested two, isolactarorufin 8-[ N
      acetyl-(2' R,3' S)-3'-phenylisoserinate] and 3-O-ethylfurandiol 8-[ N-acetyl-(2'
      R,3' S)-3'-phenylisoserinate] inhibited Herpes simplex virus type 1 (HSV-1)
      replication at low cytotoxic concentrations. Selectivity indices were: > 12.2 and
      > 106.4, respectively. Both compounds decreased also the number of cell
      divisions. Mitotic indices of the cells submitted to these compounds were:
      96/2000 and 48/1000, respectively, in comparison with control (169/2000). It
      seems that the antimitotic action of the compounds may be associated with their
      antiviral activity. Moreover, isolactarorufin 8-[ N-acetyl-(2' R,3' S)-3'
      phenylisoserinate] inhibited PHA-induced T lymphocyte proliferation.

PMID- 16636966
TI  - Lignans from Saussurea conica and their NO production suppressing activity.
AB  - Three new lignan derivatives, conicaols A and B and conicaoside, together with
      seven known compounds were identified from Saussurea conica. Their structures
      were elucidated by spectral methods including 1D and 2D NMR techniques. Six 2,3
      dibenzylbutyrolactone-type lignans were biologically evaluated, and two of them,
      arctigenin and matairesinol, showed potent activity to suppress NO production in
      vitro in LPS-activated macrophages of SD rat.

PMID- 16636967
TI  - Antiproliferative activity of Pteleopsis suberosa leaf extract and its flavonoid
      components in human prostate carcinoma cells.
AB  - In this work we describe the chemical composition of Pteleopsis suberosa
      (Combretaceae) leaf extract and its biological activity against androgen
      insensitive human prostate cancer cells (DU-145). The methanol extract of the
      plant leaves exhibited activity against tumor cell growth. Fractionation of this
      active extract led to the isolation and identification of sixteen flavonoids,
      including gallocatechin and flavonols having kaempferol, quercetin, and myricetin
      as aglycones. Among the myricetin derivatives, myricetin 3-O-(3''-acetyl)-alpha-L
      arabinopyranoside (1) and myricetin 3-O-(4''-acetyl)-alpha- L-arabinopyranoside
      (2) are now reported for the first time. Six compounds, myricetin 3-O-alpha- L
      rhamnopyranoside (4), myricetin 3-O-beta-D-galactopyranoside (7), myricetin 3-O
      (6''-galloyl)-beta-D-galactopyranoside (9), myricetin 3-O-beta-D-xylopyranoside
      (10), myricetin 3-O-alpha-L-arabinofuranoside (12), and gallocatechin (14),
      exhibited significant activity, reducing cell vitality and inducing apoptosis via
      the caspase-dependent pathway in DU-145 cells that can be, in part, correlated to
      modulation of redox-sensitive mechanisms.

PMID- 16636971
TI  - Influence of xanthohumol on the binding behavior of GABAA receptors and their
      lateral mobility at hippocampal neurons.
AB  - The influence of the xanthohumol from Humulus lupulus L. on the binding of
      muscimol-Alexa Fluor 532 (Mu-Alexa), a fluorescently labeled GABAA receptor
      agonist, was studied by fluorescence correlation spectroscopy. An incubation of
      hippocampal neurons with 75 nM of xanthohumol increased the specific Mu-Alexa
      binding by approximately 17%, which was selectively found in GABAA receptor Mu
      Alexa complexes with hindered lateral mobility [D(bound2) = (0.11 +/- 0.03)
      microm2/s] as described with midazolam.

PMID- 16636972
TI  - Effects of resveratrol on mast cell degranulation and tyrosine phosphorylation of
      the signaling components of the IgE receptor.
AB  - The molecular mechanism of how resveratrol inhibits mast cell degranulation was
      studied by examining its effects on the signaling components of the high affinity
      IgE receptor (FcepsilonRI) pathway. Resveratrol inhibited mast cell degranulation
      in a dose-dependent manner and reduced the FcepsilonRI-mediated tyrosine
      phosphorylation of ERK and PLCgamma1 but not of Syk and PLCgamma2. U-73 122 and
      PD98059, which are PLC and MEK inhibitors, also had inhibitory effects on mast
      cell degranulation. These results suggest that FcepsilonRI-mediated tyrosine
      phosphorylation of PLCgamma1 and ERK could be potential cellular targets of
      resveratrol for the inhibition of mast cell degranulation.

PMID- 16636974
TI  - Homologous and heterologous carboxyl terminal peptide (CTP) linker sequences
      enhance the secretion of bioactive single-chain bovine LH analogs.
AB  - Single chain variants of the heterodimeric gonadotropins were engineered by
      tethering the genes of the individual subunits into one polypeptide. In tethered
      human (h) gonadotropins, the carboxyl terminal peptide (CTP) of the
      choriogonadotropin (CG) beta subunit serves as an effective linker to enhance the
      secretion of the analogs compared to variants lacking the CTP. The gonadotropin
      subunits of non-primate, non-equid species lack a CTP domain that precludes the
      use of a homologous CTP in tethered analogs in many species. Here we used the
      bovine LH as a model to examine the impact of the CTP domain of the hCGbeta
      subunit (denoted as huCTP) and of a previously untranslated CTP-like sequence
      decoded from the bovine LHbeta gene on the secretion and bioactivity of tethered
      analogs. This cryptic CTP (designated boCTP) was incorporated into the bovine
      LHbeta reading frame by deletion frame-shift mutations analogous to these that
      presumably occurred in primates and equids. We genetically engineered single
      chain variants in which the beta and alpha subunit domains were linked directly
      or via the heterologous huCTP or the homologous boCTP sequences and expressed
      them in CHO cells. The data suggest that the tethered analogs were expressed and
      N-glycosylated, but unlike the huCTP, the boCTP appears as devoid of mucin O
      glycans. The incorporation of the boCTP or huCTP linkers enhanced by about 3fold
      the rate and efficiency of secretion from the transfected cells. The tether
      variants were bioactive, as estimated by induction of steroid production in
      immortalized granulosa cells expressing the rat LH receptor. Furthermore, the
      variants were about equally potent, as judged by their EC50s (0.7-0.9 ng/ml).
      Thus, the hCGbeta CTP maintains pro-secretory determinants without inhibiting
      receptor activation when applied as a linker in tethered bovine LH, implying that
      these CTP features are preserved when the domain is incorporated into non-primate
      single chain analogs. The study suggests that the boCTP and huCTP domains are
      advantageous for the secretion of tethered bovine gonadotropins, and also
      demonstrates strategies for the design of bioactive LH analogs in ruminant
      species.

PMID- 16636975
TI  - Absence of exercise-induced leptin suppression associated with insufficient
      epinephrine reserve in patients with classic congenital adrenal hyperplasia due
      to 21-hydroxylase deficiency.
AB  - OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency suffer from glucocorticoid and mineralocorticoid
      deficiency. They have insufficient epinephrine reserves and increased basal
      leptin levels and are often insulin resistant. In healthy subjects, an inhibitory
      effect of acute catecholamine elevation on the leptin plasma concentrations has
      been reported. However, it is not yet known how leptin levels respond to exercise
      in CAH patients. METHODS: We performed a cycle ergometer test in six CAH patients
      to measure the response of plasma leptin, glucose and the catecholamines,
      epinephrine (E) and norepinephrine (N), as well as their respective metabolites,
      metanephrine (M) and normetanephrine (NM), to intense exercise. RESULTS: Baseline
      leptin concentrations in CAH patients were not different from those of controls.
      Leptin levels decreased significantly with exercise in healthy controls, whereas
      they remained unchanged in CAH patients. In contrast to controls, CAH patients
      showed no rise of plasma glucose. Basal and stimulated E and M levels were
      significantly lower in CAH patients compared to controls. Baseline and stimulated
      N and NM levels were comparable, showing a significant rise after exercise. Peak
      systolic blood pressure and peak heart rate in both groups were comparable.
      CONCLUSION: CAH patients do not manifest exercise-induced leptin suppression. The
      most probable reason for this is their severely impaired epinephrine stress
      response. In addition, epinephrine deficiency is leading to secondary changes in
      various catecholamine dependent metabolic pathways, e. g., energy balance.
      Although obvious clinical sequelae are so far unknown, the catecholamine
      deficient state and the resulting hyperleptinemia might contribute to the
      severity of the disease in CAH.

PMID- 16636976
TI  - Three novel point mutations of the CYP21 gene detected in classical forms of
      congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia (CAH) [OMIM 201 910] is a group of autosomal
      recessive disorders most commonly due to 21-hydroxylase deficiency and presenting
      with a wide range of clinical manifestations. A limited number of inactivating
      pseudogene-derived mutations account for the majority of 21-hydroxylase gene (
      CYP21) mutations, additional rare mutations can be found in single families and
      small populations. We found three novel CYP21 mutations in CAH patients suffering
      from the classical form of the disease, of which one is a frameshift mutation
      (1353-1354insA) leading to a premature termination codon (K277K, Q228A...E294X),
      one results in a premature stop codon (2551C>T, R444X), and one is a missense
      mutation (2609T>C; P463L). The frameshift and premature stop mutations can be
      predicted to result in a CYP21 protein without any residual enzyme activity. To
      determine the functional consequences of the P463L mutation, the IN VITRO enzyme
      activity was studied in COS-7 cells and revealed a reduced 21-hydroxylase
      activity of 2.6+/-0.8 (SD)% for the conversion of 17-hydroxyprogesterone (17OHP)
      to 11-deoxycortisol and of 3.0+/-0.5 % for the conversion of progesterone to 11
      deoxycorticosterone (DOC). We conclude that functional analyses of unknown
      mutations provide information on the disease severity and should be always
      performed when novel CYP21 mutations are detected. Knowledge of the residual 21
      hydroxylase function improves both genetic counselling and individual clinical
      management in CAH patients.

PMID- 16636977
TI  - The diabetic charcot foot: MRI discloses bone stress injury as trigger mechanism
      of neuroarthropathy.
AB  - It is generally accepted that traumatic bone injury contributes to the clinical
      picture of neuroarthropathy of the foot in diabetes, i.e., of the diabetic
      Charcot foot. While radiology is capable of visualizing only advanced bone
      injuries, like complete fractures, magnetic resonance imaging (MRI) discloses
      bone injuries that precede complete fractures (stress bone injuries). In diabetic
      polyneuropathy, stress bone injuries are silent in terms of pain, due to the lack
      of pain sensation. At the foot, their clinical appearance is characterized by
      inflammatory swelling with little or no pain. The present paper reviews the
      contribution of MRI to the detection of bone injuries in what is called stage 0
      Charcot foot, with emphasis on the bearings for the treatment strategy.

PMID- 16636978
TI  - Inaccurate self-monitoring of blood glucose readings in patients on chronic
      ambulatory peritoneal dialysis with icodextrin.
AB  - Patients on chronic ambulant peritoneal dialysis (CAPD) are increasingly likely
      to be treated with a new solution of corn starch-derived glucose polymers called
      icodextrin. This solution involves a very low carbohydrate absorption leading to
      a better glycemic control in diabetic patients. However these glucose polymers
      pass to the blood and are metabolized to oligosaccharids which interfere with
      blood glucose in distinct capillary glucose analyzers leading to overestimation
      of glycemia. We assessed the accuracy of glucose measurements with the three most
      commonly used glucose analyzers compared to venous plasma glucose measurement at
      our institution in 8 patients (4 patients with type 2 diabetes) on CAPD using
      icodextrin. Glycemia was measured simultaneously in plasma of venous blood using
      a reference laboratory method and in capillary blood using Accu-Chek sensor
      (Rotkreuz, Switzerland) (glucose dehydrogenase method), Glucotrend 2 (Rotkreuz,
      Switzerland) (glucose-dye-oxyreductase method) and Ascensia elite (Zurich,
      Switzerland) (glucose oxidase method) glucose analyzers. Only glucose readings
      with Ascensia elite correspond correctly with venous plasma glucose results (+0.3
      mmol/l; n. s.), whereas glycemia was significantly overestimated by Accu-Chek
      sensor (+4.3 mmol/l; p<0.0001) and Glucotrend 2 glucose analyzers (+3.7 mmol/l;
      p<0.0001). Thus we conclude that distinct glucose analyzers overestimate real
      blood glucose concentration and are not suitable for monitoring glycemia in
      patients on CAPD with icodextrin. On the basis of our results, these patients
      should use glucose analyzers using glucose oxidase methods. All glucose analyzers
      should be cross-checked with a laboratory reference method before the application
      in patients on CAPD with icodextrin is recommended.

PMID- 16636979
TI  - C-reactive protein is a strong independent predictor of death in type 2 diabetes:
      association with multiple facets of the metabolic syndrome.
AB  - INTRODUCTION: It has been suggested that atherosclerotic vascular disease is a
      chronic inflammatory process. The aim of this study was to investigate the
      importance of C-reactive protein (CRP) as a cardiovascular risk marker and
      predictor of death, as well as its relation to other factors of the metabolic
      syndrome in a cohort of type 2 diabetic patients at high risk of severe
      macrovascular complications. MATERIAL AND METHODS: 592 patients, aged 55 to 74
      years (311 men, 281 women), with signs and symptoms of circulation deficits were
      examined by duplex ultrasound for suspected cerebrovascular and peripheral
      arterial disease and followed over a period of 5 years. At baseline, 292 patients
      of the total group had type 2 diabetes (49.3%). Ischemic heart disease was
      present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial
      disease in 39.7% of the subjects. RESULTS: During the observation period, 104
      patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial
      infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients
      (13.3%) and amputations because of gangrene were unavoidable in 24 patients
      (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and
      cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13
      13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4
      [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor
      the data of diabetic metabolic control were able to improve prediction. CRP was
      correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C
      peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria
      (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type
      2 diabetic patients. CONCLUSIONS: CRP seems to be a better predictor of death and
      cardiovascular events than traditional risk factors or parameters of metabolic
      control in type 2 diabetic patients at high risk for cardiovascular endpoints.
      Additionally, CRP is associated with several facets of the metabolic syndrome.

PMID- 16636980
TI  - Follow-up of pregnancy in acromegalic women: different presentations and
      outcomes.
AB  - Pregnancy in acromegaly is a rather rare event since the fertility is reduced in
      acromegalic women. Besides, metabolic complications of acromegaly are harmful to
      both mother and fetus. Little is known about the outcome of pregnancy in
      acromegalic women. Here, we report seven cases of pregnancy out of 48 acromegalic
      women followed for 16 years. At diagnosis, five patients had macroadenoma, one
      patient had microadenoma and the size of the tumor was not documented in one
      patient. In one patient, acromegaly was initially diagnosed during pregnancy at
      29 weeks. When she was 33 weeks, she developed pituitary apoplexy and had an
      emergency transsphenoidal resection of her macroadenoma during which she also had
      a cesarian section and delivered a healthy baby girl. In the remaining six
      patients, pregnancy occurred 6 to 64.5 months after the adenoma resection. Three
      patients received radiotherapy before getting pregnant. In three patients,
      pregnancy occurred during bromocriptine treatment and the drug was withdrawn. In
      one patient, pregnancy occurred during chronic octreotide treatment and
      therapeutic abortion was performed. In another patient, therapeutic abortion was
      performed because of uncontrolled disease. In the remaining four patients, there
      were neither worsening of symptoms nor tumor growth. All four patients gave birth
      to full-term healthy infants. Out of our seven patients, two developed
      gestational diabetes mellitus which was controlled with diet. None of the
      patients had coronary artery disease, hypertension or dyslipidemia. These cases
      show that pregnancy might be uneventful in acromegalic women when the disease is
      controlled with prior surgery and radiotherapy.

PMID- 16636981
TI  - A primary adrenal non-Hodgkin's lymphoma presenting as an incidental adrenal
      mass.
AB  - The primary adrenal localization of a non-Hodgkin's lymphoma (NHL) is a rare
      event. We report the case of a 70-yr-old woman, who was admitted at our Institute
      for a hormonal evaluation after the incidental discovery of a right adrenal mass
      during ultrasonography (US) performed for cardiovascular disease. At the physical
      examination, no sign of adrenal hyperfunction was present. She showed only an
      androgenetic alopecia and her blood pressure was 180/70 mm Hg, with an arrhythmic
      heart rate of 100 beats/min. No alterations in hormonal and biochemical data were
      observed. US studies showed a right adrenal mass (major diameter 16 mm), and an
      abdominal computed tomography (CT) scan confirmed this solid lesion (major
      diameter 15 mm) with a high density. [75Se] methylnorcholesterol adrenal
      scintigraphy exhibited a normal symmetrical radiotracer uptake. After 8 months of
      follow-up, an abdominal CT scan demonstrated a significant increase of the right
      adrenal mass (major diameter: 40 mm), with a solid tissue density and enhancement
      after i.v. contrast. [75Se] methylnorcholesterol adrenal scintigraphy showed an
      absent uptake on the right side versus the contralateral side. The hematological,
      hormonal and radiological evaluation did not reveal any sign of malignancy. Owing
      to the mass enlargement and the modification of scintigraphic pattern, the
      patient underwent unilateral adrenalectomy. Histological examination revealed a
      primary diffuse large B-cell NHL (REAL classification) of the adrenal gland.
      After surgery, she underwent a combined polychemotherapy (cyclophospamide,
      adriamycin, vincristine and prednisone) and subsequently one cycle of
      radiotherapy. At present, the patient is in good conditions and there are no
      signs or symptoms of recurrent disease.

PMID- 16636984
TI  - The era of microbiology: a golden phoenix.
AB  - The discoveries over the last decade have demonstrated that microbiology is a
      central scientific discipline with practical applications in agriculture,
      medicine, bioremediation, biotechnology, engineering, and other fields. It is
      clear that the roles of microbes in nature are so diverse that the process of
      mining this genetic variation for new applications will continue long into the
      future. Moreover, the rapid rate of microbial evolution ensures that there will
      be no permanent solution to agricultural, medical, or environmental problems
      caused by microbes. These problems will demand a continual stream of creative new
      approaches that evolve along with the microbes. Thus, the excitement of this
      field will continue long into the future. However, these opportunities and
      imperatives demand a deep understanding of basic microbial physiology, genetics,
      and ecology. Major challenges that lay ahead are to impart the broad training
      needed to entice and enable the next generation of microbiologists, and to
      educate the public and government representatives about the continued and
      critical importance of this field for health and the economy.

PMID- 16636985
TI  - Gene clusters for beta-lactam antibiotics and control of their expression: why
      have clusters evolved, and from where did they originate?
AB  - While beta-lactam compounds were discovered in filamentous fungi, actinomycetes
      and gram-negative bacteria are also known to produce different types of beta
      lactams. All beta-lactam compounds contain a four-membered beta-lactam ring. The
      structure of their second ring allows these compounds to be classified into
      penicillins, cephalosporins, clavams, carbapenens or monobactams. Most beta
      lactams inhibits bacterial cell wall biosynthesis but others behave as beta
      lactamase inhibitors (e.g., clavulanic acid) and even as antifungal agents (e.g.,
      some clavams). Due to the nature of the second ring in beta-lactam molecules, the
      precursors and biosynthetic pathways of clavams, carbapenems and monobactams
      differ from those of penicillins and cephalosporins. These last two groups,
      including cephamycins and cephabacins, are formed from three precursor amino
      acids that are linked into the alpha-aminoadipyl-L-cysteinyl-D-valine tripeptide.
      The first two steps of their biosynthetic pathways are common. The intermediates
      of these pathways, the characteristics of the enzymes involved, the lack of
      introns in the genes and bioinformatic analysis suggest that all of them should
      have evolved from an ancestral gene cluster of bacterial origin, which was surely
      transferred horizontally in the soil from producer to non-producer
      microorganisms. The receptor strains acquired fragments of the original bacterial
      cluster and occasionally inserted new genes into the clusters, which once
      modified, acquired new functions and gave rise to the final compounds that we
      know. When the order of genes in the Streptomyces genome is analyzed, the
      antibiotic gene clusters are highlighted as gene islands in the genome.
      Nonetheless, the assemblage of the ancestral beta-lactam gene cluster remains a
      matter of speculation.

PMID- 16636986
TI  - Towards the identification of the common features of bacterial biofilm
      development.
AB  - Microorganisms can live and proliferate as individual cells swimming freely in
      the environment, or they can grow as highly organized, multicellular communities
      encased in a self-produced polymeric matrix in close association with surfaces
      and interfaces. This microbial lifestyle is referred to as biofilms. The intense
      search over the last few years for factors involved in biofilm development has
      revealed that distantly related bacterial species recurrently make use of the
      same elements to produce biofilms. These common elements include a group of
      proteins containing GGDEF/EAL domains, surface proteins homologous to Bap of
      Staphylococcus aureus, and some types of exopolysaccharides, such as cellulose
      and the poly-beta-1,6-N-acetylglucosamine. This review summarizes current
      knowledge about these three common elements and their role in biofilm
      development.

PMID- 16636987
TI  - Immuno-electron microscopic quantification of the fucoxanthin chlorophyll a/c
      binding polypeptides Fcp2, Fcp4, and Fcp6 of Cyclotella cryptica grown under low-
      and high-light intensities.
AB  - The diatom Cyclotella cryptica was grown under low- and high-intensity white
      light of 50 and 500 micromol photons m-2 s-1, respectively. Western
      immunoblotting showed that the diatom adapted its light-harvesting apparatus,
      giving rise to different amounts of distinct fucoxanthin chlorophyll a/c binding
      polypeptides (Fcp). The amount of Fcp2 was approximately two-fold higher under
      low-light than under high-light conditions, whereas the amount of Fcp6 increased
      four- to five-fold under high-light conditions. For Fcp4, no significant
      differences were detected in response to either light regime. Cells of Cyclotella
      grown under high- and low-light intensity were subjected to immunoelectron
      microscopy. Quantification of the gold label, expressed as gold particles per
      microm2, confirmed the results obtained by Western immunoblotting. Exposure to
      low light resulted in the detection of approximately six times more Fcp2-bound
      gold particles per microm2 in thylakoid membranes, whereas in cells grown under
      high light the number of Fcp6-bound gold particles increased ten-fold. For Fcp4,
      similar amounts of gold particles per microm2 were counted under the two light
      regimes. These immunocytochemical results confirmed molecular data derived from
      phylogenetic analyses of the sequences of genes encoding fucoxanthin chlorophyll
      a/c binding polypeptides (fcp genes) and from measurements of steady-state fcp
      mRNA concentrations. The results show that Fcp2 and Fcp6 accumulate under low-
      and high-light intensity, respectively, whereas Fcp4 seems to be constitutively
      synthesized.

PMID- 16636988
TI  - ATP level variations in heterotrophic bacteria during attachment on hydrophilic
      and hydrophobic surfaces.
AB  - A survey of the extracellular ATP levels of 86 heterotrophic bacteria showed that
      gram-negative bacteria of the genera Sulfitobacter, Staleya, and Marinobacter
      secreted elevated amounts of extracellular ATP, ranging from 6.0 to 9.8 pM
      ATP/colony forming unit (cfu), and that gram-positive bacteria of the genera
      Kocuria and Planococcus secreted up to 4.1 pM ATP/cfu. Variations in the levels
      of extracellular and intracellular ATP-dependent luminescence were monitored in
      living cells of Sulfitobacter mediterraneus ATCC 700856T and Planococcus
      maritimus F 90 during 48 h of attachment on hydrophobic (poly[tert-butyl
      methacrylate], PtBMA) and hydrophilic (mica) surfaces. The bacteria responded to
      different polymeric surfaces by producing either intracellular or extracellular
      ATP. The level of intracellular ATP in S. mediterraneus ATCC 700856T attached to
      either surface was as high as 50-55 pM ATP/cfu, while in P. maritimus F 90 it was
      120 and 250 pM ATP/cfu on PtBMA and mica, respectively. S. mediterraneus ATCC
      700856T generated about 20 and 50 pM of extracellular ATP/cfu on PtBMA and mica,
      respectively, while the amount generated by P. maritimus F 90 was about the same
      for both surfaces, 6 pM ATP/cfu. The levels of extracellular ATP generated by S.
      mediterraneus during attachment on PtBMA and mica were two to five times higher
      than those detected during the initial screening. High-resolution atomic force
      microscopy imaging revealed a potentially interesting correlation between the
      porous cell-surface of certain alpha- and gamma-proteobacteria and their ability
      to secrete high amounts of ATP.

PMID- 16636989
TI  - The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and
      Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans.
AB  - Orally ingested probiotic bacteria are able to modulate the immune system.
      However, differences exist in the immunomodulatory effects of different probiotic
      strains. Moreover, different regulatory effects, which depend on the health
      status of the consumer, have been identified. This work describes a randomized,
      double-blind, placebo-controlled human clinical trial to investigate the immune
      effects on healthy people of a fermented product containing two new probiotic
      strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT
      5711, which was compared with another fermented product, a standard yogurt.
      Consumption of either the new product or yogurt increased the proportion of
      phagocytic cells, including monocytes and neutrophils, as well as their
      phagocytic activity. However, combination of the product containing the strains
      L. gasseri CECT 5714 and L. coryniformis CECT 5711 also induced an increase in
      the proportion of natural killer (NK) cells and in IgA concentrations. The
      effects were higher after two weeks of treatment than after 4 weeks, which
      suggests regulation of the immune system. In addition, the new product enhanced
      immunity in the participants to a greater extent than did the control standard
      yogurt.

PMID- 16636990
TI  - Serotypes, virulence genes, and PFGE patterns of enteropathogenic Escherichia
      coli isolated from Cuban pigs with diarrhea.
AB  - Thirty-six enteropathogenic Escherichia coli strains isolated from Cuban pigs
      with diarrhea were serotyped and screened by PCR for the presence of virulence
      genes. The 36 isolates belonged to 11 O serogroups and 14 O:H serotypes, with 53%
      of the isolates belonging to only two serotypes: O141:H- (13 isolates) and
      O157:H19 (6 isolates). Genes coding for STb, STa, VT2e, and LT toxins were
      identified in 69, 61, 53, and 6% of the isolates, respectively. The most
      prevalent fimbrial adhesin was F18, detected in 22 (61%) isolates. The gene
      encoding F6 (P987) colonization factor was identified in three (8%) isolates.
      None of the 36 isolates assayed contained genes encoding F4 (K88), F5 (K99), or
      F41. The seropathotype O141:H-:STa/STb/VT2e/F18 (13 isolates) was the most
      frequently detected, followed by O157:H19:VT2e/F18 (5 isolates). A genetic
      diversity study, carried out by pulsed-field gel electrophoresis (PFGE) of 24
      representative isolates, revealed 21 distinct restriction patterns clustered in
      18 groups (I-XVIII). Isolates of the same serotype were placed together in a
      dendrogram, but isolates of serotype O157:H19 showed a high degree of
      polymorphism. The results of this study demonstrate the presence in Cuba of
      different clusters among one of the most prevalent serotypes isolated from pigs
      with diarrhea. Further experiments are needed to determine whether some of these
      clusters have appeared recently; if so, their evolution, as well as their
      possible association with pathogenicity in farms should be studied.

PMID- 16636991
TI  - Light-induced rhythmic changes in thermotolerance in stationary-phase cells of
      Candida utilis.
AB  - In synchronized light-dark cycles, stationary-phase cultures of the budding yeast
      Candida utilis were able to survive heat treatment at 50 degees C with an
      apparent circadian-like rhythm related to the onset of light. However, in
      continuous darkness this pattern did not run freely and was markedly dampened. We
      discuss these findings in terms of the potential circadian control of heat
      tolerance, which has been described in the fission yeast Schizosaccharomyces
      pombe. Our results suggest that the resistance pattern observed in C. utilis is
      most likely an adaptive response to the light-induced generation of reactive
      oxygen species rather than the occurrence of a truly endogenous circadian rhythm.

PMID- 16636992
TI  - Genetic diversity and recombination within populations of Fusarium
      pseudograminearum from western Canada.
AB  - Genetic diversity within populations of Fusarium pseudograminearum isolated from
      wheat grains from the Canadian provinces of Alberta and Saskatchewan was
      investigated. Three restriction enzymes (EcoRI, HaeIII, and PstI) were used to
      carry out restriction analysis of the nuclear ribosomal DNA (nrDNA) intergenic
      spacer region (IGS region) and eight primers were used to generate inter-simple
      sequence-repeat (ISSR) molecular markers. Our study indicated substantially high
      genetic diversity within these two populations, but low genetic differentiation
      and frequent gene flow among populations. The IGS data showed no genetic
      distinction between the two Alberta populations and only minor genetic
      differentiation between the Saskatchewan and Alberta populations. Analysis of
      molecular variance indicated that most genetic variability resulted from
      differences among isolates within populations. Multilocus linkage disequilibrium
      analysis suggested a panmictic population genetic structure and the occurrence of
      significant recombination in F. pseudograminearum. Regular gene flow and random
      mating between isolates from different populations could result in novel
      genotypes with both improved pathological and biological traits.

PMID- 16636993
TI  - Grassi versus Ross: who solved the riddle of malaria?

PMID- 16636994
TI  - Enhanced detection of sulfo-peptides as onium salts in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - A new two-component system, consisting of a matrix and an onium salt as comatrix,
      is described for detection of sulfo-peptides in the positive mode by matrix
      assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS).
      Binary iodonium salts were superior to quaternary phosphonium salts in terms of
      suppression of desulfation and salt formation with the carboxyl group. Of the
      iodonium salts examined, bis(4-tert-butylphenyl)iodonium (BTI)
      hexafluorophosphate and bromide were most effective in giving intensive molecular
      ion signals in the form of [M(BTI)+BTI](+). The conditions optimized for O
      sulfated tyrosine-containing peptides could be applicable for O-sulfated serine-
      and threonine-containing peptides. In the case of a phospho-peptide, a molecular
      ion appeared more intensively as a proton adduct than as a BTI adduct.

PMID- 16636995
TI  - Investigating the structural properties of amyloid-like fibrils formed in vitro
      from beta2-microglobulin using limited proteolysis and electrospray ionisation
      mass spectrometry.
AB  - The protein beta(2)-microglobulin (beta(2)m) aggregates to form classical amyloid
      fibrils in patients undergoing long-term haemodialysis. Amyloid-like fibrils with
      a cross-beta fold can also be formed from wild-type beta(2)m under acidic
      conditions in vitro. The morphology of such fibrils depends critically on the
      conditions used: incubation of beta(2)m in low ionic strength buffers at pH 2.5
      results in the formation of long (microm), straight fibrils while, at pH 3.6,
      short (<500 nm) fibrils form. At higher ionic strengths (0.2-0.4 M) at pH 1.5
      3.6, the fibrils have a distinct curved and nodular morphology. To determine the
      conformational properties of beta(2)m within in vitro fibrils of different
      morphologies, limited proteolysis of each fibril type using pepsin was performed
      and the resulting peptide fragments identified by tandem mass spectrometry. For
      comparison, the proteolytic degradation patterns of monomeric beta(2)m and seven
      synthetic peptides spanning the entire sequence of the intact protein were
      similarly analysed. The results show that fibrils with different morphologies
      result in distinct digestion patterns. While the curved, worm-like fibrils are
      relatively weakly protected from proteolysis, the long, straight fibrils formed
      at pH 2.5 at low ionic strength show only a single cut-site at Val9,
      demonstrating that substantial refolding of the initially acid-denatured and
      unprotected state of beta(2)m occurs during assembly. The data demonstrate that
      the organisation of the polypeptide chain in fibrils with different morphological
      features differs considerably, despite the fact that the fibrils possess a common
      cross-beta architecture.

PMID- 16636996
TI  - Cell-based assay for screening 11beta-hydroxysteroid dehydrogenase inhibitors
      using liquid chromatography/tandem mass spectrometry detection.
AB  - Cortisol is an important glucocorticoid that regulates many physiological
      pathways by activating various intracellular receptors. The type 1 isozyme of
      11beta-hydroxysteroid dehydrogenase (11beta-HSD1) functions in vivo predominantly
      as a reductase by converting cortisone into cortisol. A high-throughput liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to
      screen for inhibitors of 11beta-HSD1 by monitoring cortisol and cortisone
      simultaneously. The injection cycle time can be as fast as 1 min/sample, making
      it amenable to the analysis of large numbers of the cell-assay samples in the
      screening of 11beta-HSD inhibitors. The reductase and dehydrogenase activities of
      11beta-HSD1 are assessed separately.

PMID- 16636997
TI  - Dissociation of biomolecules using a ultraviolet matrix-assisted laser
      desorption/ionisation time-of-flight/curved field reflectron tandem mass
      spectrometer equipped with a differential-pumped collision cell.
AB  - A commercial matrix-assisted laser desorption/ionisation time-of-flight (MALDI
      ToF) instrument equipped with a curved field reflectron (CFR) was modified in
      order to perform collision-induced dissociation (CID) on a variety of
      biomolecules. The incorporation of a high-resolution ion gate together with a
      collision cell within the field-free region allowed tandem mass analysis (MS/MS),
      without the necessity to decelerate the precursor ions prior to activation. The
      simultaneous detection of all product ions remained possible by using the CFR. To
      test the MS/MS performances, ACTH (fragment 1-17), a complex high mannose
      carbohydrate (Man)(8)(GlcNac)(2) and a lysophosphatidylcholine lipid (18:1) were
      analysed on the modified instrument. Direct comparison with the low-energy
      product ion spectra, acquired on a MALDI quadrupole ion trap (QIT) two-stage
      reflectron time-of flight (ReToF) mass spectrometer, showed significant
      differences in the types of product ions observed. The additional ions detected
      were a clear indication of the high-energy fragmentation processes occurring in
      the collision cell.

PMID- 16636998
TI  - The characterisation of selected antidepressant drugs using electrospray
      ionisation with ion trap mass spectrometry and with quadrupole time-of-flight
      mass spectrometry and their determination by high-performance liquid
      chromatography/electrospray ionisation tandem mass spectrometry.
AB  - The electrospray ionisation ion trap tandem mass spectrometry (ESI-MS(n)) of
      selected antidepressant drugs, i.e., citalopram, fluoxetine, mirtazapine,
      paroxetine, sertraline, and venlafaxine, has been investigated. Sequential
      product ion fragmentation experiments (MS(n)) have been performed in order to
      elucidate the degradation pathways for the [M+H](+) ions and their predominant
      product ions. These MS(n) experiments show certain characteristic fragmentations
      in that functional groups are generally cleaved from the ring systems as
      molecules such as H(2)O, amines and phenols. When an aromatic entity is present
      in a drug molecule together with a nitrogen-containing saturated ring structure
      as with mirtazapine, fragmentation initially occurs at the latter ring with the
      former being predictably resistant to fragmentation. Also, when an amine
      containing drug molecule such as fluoxetine also contains a functional group,
      which liberates a phenol with a significantly lower DeltaH(f) (0) value than that
      of the corresponding amine, the phenol is preferentially liberated. The
      structures of product ions proposed for ESI-MS(n) can be supported by
      electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (ESI
      QToF-MS/MS). These molecules can be identified and determined in mixtures at low
      ng/mL concentrations by the application of high-performance liquid
      chromatography/electrospray ionisation tandem mass spectrometry (HPLC/ESI-MS(2)),
      which can also be used for their analysis in hair samples.

PMID- 16636999
TI  - Deconvolution filters to enhance resolution of dense time-of-flight survey
      spectra in the time-lag optimization range.
AB  - By applying time-domain filters to time-of-flight (TOF) mass spectrometry
      signals, we have simultaneously smoothed and narrowed spectra resulting in
      improved resolution and increased signal-to-noise ratios. This filtering
      procedure has an advantage over detailed curve fitting of spectra in the case of
      large dense spectra, when neither the location nor the number of mass peaks is
      known a priori. This time series method is directly applicable in the time lag
      optimization range, where point density per peak is constant. We present a
      systematic methodology to optimize the filters according to any desired figure of
      merit, illustrating the procedure by optimizing the signal-to-noise per unit
      bandwidth of matrix-assisted laser desorption/ionization (MALDI) data. We also
      introduce a nonlinear filter that reduces the spurious structure that often
      accompanies deconvolution filters. The net result of the application of these
      filters is that we can identify new structures in dense MALDI-TOF data, clearly
      showing small adducts to heavy biomolecules.

PMID- 16637000
TI  - Quantification of clopidogrel in human plasma by sensitive liquid
      chromatography/tandem mass spectrometry.
AB  - A simple, sensitive and rapid high-performance liquid chromatography/positive
      electrospray ionization tandem mass spectrometry method was developed and
      validated for the assay of clopidogrel in human plasma. Following liquid-liquid
      extraction, the analytes were separated using an isocratic mobile phase on a
      reversed-phase column and analyzed by mass spectrometry in the multiple reaction
      monitoring mode using the respective [M+H](+) ions, m/z 322/212 for clopidogrel
      and m/z 264/154 for the internal standard. The assay exhibited a linear dynamic
      range of 5-6000 pg/mL for clopidogrel in human plasma. The lower limit of
      quantification was 5 pg/mL with a relative standard deviation of less than 8%.
      Acceptable precision and accuracy were obtained for concentrations over the
      standard curve range. A run time of 2.5 min for each sample made it possible to
      analyze more than 400 human plasma samples per day. The validated method has been
      successfully used to analyze human plasma samples for application in
      pharmacokinetic, bioavailability or bioequivalence studies.

PMID- 16637001
TI  - Electron ionization mass spectra of phosphorus-containing heterocycles. II.
      1,2,3,4,4a,5,6,7,8,8a-decahydro-1,3,2-benzodiazaphosphinine 2-oxides.
AB  - The electron ionization mass spectra of cis- and trans-fused
      1,2,3,4,4a,5,6,7,8,8a-decahydro-1,3,2-benzodiazaphosphinine 2-oxides (1-17) were
      recorded, and the fragmentation pathways were established and compared with those
      of 1,4,4a,5,6,7,8,8a-octahydro-2H-3,1,2-benzoxazaphosphinine 2-oxides. In
      general, the mass spectral behaviors of the isomeric compounds were very similar
      and it was mostly impossible to differentiate them from each other on the basis
      of the relative abundances of their characteristic fragment ions. The compounds
      in which R(2) = Ph or OPh exhibited a series of common fragments, e.g.
      [R(2)H](+), R(2)PONHR(1(3)+), [M-C(3)H(7)](+) and [M-C(4)H(9)](+), the latter two
      ions being present in the spectra of only two of the derivatives with an
      N(CH(2)CH(2)Cl)(2) substituent on the P atom. When R(2) = Ph, numerous other
      alkyl radicals, alkenes and a cycloalkane were also ejected and these compounds
      also lost NH(2), NH(3), CH(3)N, CH(4)N or CH(3)NH(2). The compounds with an
      N(CH(2)CH(2)Cl)(2) substituent on the P atom most closely resembled their 3,1,2
      O,N,P analogs in respect of the dominant role of this substituent.

PMID- 16637002
TI  - Comparison of the fragmentation pattern induced by collisions, laser excitation
      and electron capture. Influence of the initial excitation.
AB  - Collision-induced dissociation, laser-induced dissociation and electron-capture
      dissociation are compared on a singly and doubly protonated pentapeptide. The
      dissociation spectrum depends on the excitation mechanism and on the charge state
      of the peptide. The comparison of these results with the conformations obtained
      from Monte Carlo simulations suggests that the de-excitation mechanism following
      a laser or an electron-capture excitation is related to the initial geometry of
      the peptide.

PMID- 16637003
TI  - Resampling and deconvolution of linear time-of-flight records for enhanced
      protein profiling.
AB  - We have developed a peak deconvolution strategy that is applicable to the full
      mass range of a time-of-flight (TOF) spectrum. This strategy involves resampling
      a spectrum to create a time series that has equal peak widths (in time) across
      the entire spectrum, and then using the deconvolution filters we have previously
      described. We use this technique to deconvolve the protein mass spectra for blood
      serum and cell lysates acquired on three separate TOF instruments. Following
      deconvolution, we resolve spectral structures consistent with expected events
      such as multiply charged ions, matrix adducts and post-translational protein
      modifications. The deconvolution procedure produces a 40% improvement in the
      resolution and enhanced experimental sensitivity over the full length of the
      linear TOF record, up to m/z 150 000. This approach is particularly appropriate
      for automated data analysis and peak detection in dense TOF spectra.

PMID- 16637004
TI  - Signal improvement in elemental analyzer/continuous flow isotope ratio mass
      spectrometry for samples with low sulfur contents using a pre-concentration
      technique for on-line concentration adjustment.
AB  - Elemental analyzer/continuous flow isotope ratio mass spectrometry (EA/CF-IRMS)
      has become a standard procedure for the determination of delta(34)S values.
      Common procedures are, however, frequently less than satisfactory for organic as
      well as for mineral samples with very low concentrations of sulfur (<2000 ppm).
      Here we present a method which employs cold trapping of SO(2) to adjust the gas
      concentration for subsequent isotope signature determination. Analytical accuracy
      is comparable with common EA/CF-IRMS analysis without trapping, showing a
      precision of better than +/-0.4 per thousand in delta(34)S (1 SD). The virtual
      absence of memory effects was established by analyzing adjacent samples
      exhibiting a large difference in delta(34)S and by prolonged freezing of the
      carrier gas, yielding virtually no S concentration peak. The method was tested
      using less than 15% (6 microg) of the S required for a conventional isotope
      analysis at comparable signal intensity. Even smaller samples can be analyzed
      with high precision. This facilitates the on-line delta(34)S determination in
      small biological and mineral samples, minimizing matrix effects in various
      materials including sandstone, soil, and plant samples.

PMID- 16637005
TI  - Proteomic analysis of recurrent spontaneous abortion: Identification of an
      inadequately expressed set of proteins in human follicular fluid.
AB  - Recurrent spontaneous abortion (RSA), defined as the loss of three or more
      consecutive pregnancies prior to the 20th week of gestation, affects up to 5% of
      the child-bearing population. To investigate the proteins associated with RSA,
      the protein expression in human follicular fluid was analyzed using 2-DE.
      Follicular fluid contains a variety of biologically important proteins for oocyte
      fertilization and follicle maturation in the mammalian reproductive process.
      Therefore, it can be used as a provisional source for identifying proteins
      involved in RSA. In this study, we identified five aberrantly expressed proteins
      (complement component C3c chain E, fibrinogen gamma, antithrombin,
      angiotensinogen, and hemopexin precursor) in follicular fluid from RSA patients
      with MALDI-TOF-MS and nano-LC MS/MS. Western blot analysis confirmed that the
      protein expression level of fibrinogen gamma and antithrombin was less in
      follicular fluid from RSA patients than those from normal controls.
      Semiquantitative RT-PCR and real-time PCR analyses revealed that mRNA level of
      these coagulation factors was also decreased significantly in chorionic villi of
      RSA patients compared with normal samples. Taken all together, it is likely that
      coagulation factors (fibrinogen gamma and antithrombin) play an important role in
      maintaining the normal pregnancy.

PMID- 16637006
TI  - Pseudomonas putida KT2440 responds specifically to chlorophenoxy herbicides and
      their initial metabolites.
AB  - Pseudomonas putida KT2440 is often used as a model to investigate toxicity
      mechanisms and adaptation to hazardous chemicals in bacteria. The objective of
      this paper was to test the impact of the chlorophenoxy herbicides 2,4
      dichlorophenoxyacetic acid (2,4-D) and 2-(2,4-dichlorophenoxy)propanoic acid
      (DCPP) and their metabolites 2,4-dichlorophenol (DCP) and 3,5-dichlorocatechol
      (DCC), on protein expression patterns and physiological parameters. Both
      approaches showed that DCC has a different mode of action and induces different
      responses than DCPP, 2,4-D and DCP. DCC was the most toxic compound and was
      active as an uncoupler of oxidative phosphorylation. It repressed the synthesis
      of ferric uptake regulator (Fur)-dependent proteins, e.g. fumarase C and L
      ornithine N5-oxygenase, which are involved in oxidative stress response and iron
      uptake. DCPP, 2,4-D and DCP were less toxic than DCC. They disturbed oxidative
      phosphorylation to a lesser extent by a yet unknown mechanism. Furthermore, they
      repressed enzymes of energy-consuming biosynthetic pathways and induced membrane
      transporters for organic substrates. A TolC homologue component of multidrug
      resistance transporters was found to be induced, which is probably involved in
      the removal of lipophilic compounds from membranes.

PMID- 16637007
TI  - Normal responses to specific NOD1-activating peptidoglycan agonists in the
      presence of the NOD2 frameshift and other mutations in Crohn's disease.
AB  - Both NOD2/CARD15 alleles are mutated in approximately 10% of Crohn's disease
      patients, causing loss of functional responses to low-dose muropeptide agonists.
      We hypothesized that NOD2 mutations may also impair NOD1/CARD4 responses,
      supported by data suggesting NOD2 1007fs/1007fs patients had reduced responses to
      a putative NOD1 agonist, diaminopimelic acid-containing muramyl tripeptide (M
      TriDAP). We measured peripheral blood mononuclear cell (n = 8 NOD2 wild type, n =
      4 1007fs/1007fs, n = 6 702Trp/1007fs, n = 5 702Trp/702Trp, n = 3 908Arg/1007fs)
      responses to NOD1 agonists alone (IL-8/TNF-alpha), and agonist enhancement of
      lipopolysaccharide (LPS) responses (IL-1beta). Significant responses were seen
      with M-TriDAP at 10 nM (as with NOD2 agonists), but only at > or =100 nM with
      FK565/TriDAP. M-TriDAP induced IL-8/TNF-alpha secretion, and enhancement of LPS
      IL-1beta responses was significantly reduced between NOD2 double mutation
      carriers versus healthy controls, whereas there was no difference with FK565 or
      TriDAP stimulation, or between 1007fs/1007fs cells and other genotypes. M-TriDAP
      contains both NOD1 (gamma-D-Glu-mesoDAP) and NOD2 (MurNAc-L-Ala-D-Glu) minimal
      structures whereas FK565/TriDAP contain only NOD1 activating structures. M-TriDAP
      has dual NOD1/NOD2 agonist activity in primary cells, possibly due to different
      intracellular peptidoglycan processing compared to the HEK293 cell system
      typically used for agonist specificity studies. Responses to specific NOD1
      agonists are unaffected by NOD2 genotype, suggesting independent action of the
      NOD1 and NOD2 pathways.

PMID- 16637008
TI  - LACK-reactive CD4+ T cells require autocrine IL-2 to mediate susceptibility to
      Leishmania major.
AB  - Mice from most inbred strains are resistant to infection with Leishmania major
      whereas mice from BALB strains are highly susceptible. Resistance and
      susceptibility result from the development of Th1 or Th2 cells, respectively. In
      this report, we document an IL-2 mRNA burst, preceding the reported early IL-4
      response, in draining lymph nodes of susceptible mice infected with L. major.
      Neutralization of IL-2 during the first days of infection redirected Th1 cell
      maturation and resistance to L. major, through interference with the rapid IL-4
      transcription in Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4(+)
      cells. A burst of IL-2 transcripts also occurred in infected C57BL/6 mice that do
      not mount an early IL-4 response. However, although the LACK protein induced IL-2
      transcripts in susceptible mice, it failed to trigger this response in resistant
      C57BL/6 mice. Reconstitution experiments using C.B.-17 SCID mice and LACK
      reactive CD4(+) T cells from IL-2(-/-) BALB/c mice showed that triggering of the
      early IL-4 response required autocrine IL-2. Thus, in C57BL/6 mice, the inability
      of LACK-reactive CD4(+) T cells to express early IL-4 mRNA transcription,
      important for disease progression, appears due to an incapacity of these cells to
      produce IL-2.

PMID- 16637009
TI  - Unidirectional development of CD8+ central memory T cells into protective
      Listeria-specific effector memory T cells.
AB  - Three distinct subsets of antigen-experienced CD8(+) T cells have been identified
      so far: short-living effector T cells (T(EC)) and two long-living subsets,
      described as central (T(CM)) and effector memory (T(EM)) T cells. The lineage
      relationships of these subpopulations as well as their involvement in protection
      have not yet been conclusively determined. We recently described a novel marker
      combination (CD127 and CD62L) to identify all three major CD8(+) T cell subsets
      in mice infected with Listeria monocytogenes (L.m.). Extensive lineage
      relationship analyses on highly purified subpopulations after in vitro and in
      vivo stimulation demonstrated that T(CM) can develop into T(EM) or T(EC), whereas
      T(EM) can only progress to T(EC) cells. Short-living T(EC) never regained a T(EM)
      or T(CM) phenotype. These data strongly suggest a hierarchical and unidirectional
      order of developmental stages. In vivo priming protocols that preferentially
      induced one of the different CD8(+) T cell subsets demonstrated that predominance
      of T(EM) (CD40 stimulation) correlated best with effective protection against
      L.m., whereas generation of neither T(CM) (by immunization with heat-killed L.m.)
      nor T(EC) (by systemic co-administration of CpG during primary infection)
      conferred substantial long-term protective immunity. These findings have
      important implications for the design of more effective T cell-based vaccines.

PMID- 16637010
TI  - Proteomic analysis of the anterior cingulate cortex in the major psychiatric
      disorders: Evidence for disease-associated changes.
AB  - Abnormalities of the anterior cingulate cortex have previously been described in
      schizophrenia, major depressive disorder and bipolar disorder. In this study 2-DE
      was performed followed by mass spectrometric sequencing to identify disease
      specific protein changes within the anterior cingulate cortex in these
      psychiatric disorders. The 2-DE system comprised IPGs 4-7 and 6-9 in the first,
      IEF dimension and SDS-PAGE in the second dimension. Resultant protein spots were
      compared between control and disease groups. Statistical analysis indicated that
      35 spots were differentially expressed in one or more groups. Proteins comprising
      26 of these spots were identified by mass spectroscopy. These represented 19
      distinct proteins; aconitate hydratase, malate dehydrogenase, fructose
      bisphosphate aldolase A, ATP synthase, succinyl CoA ketoacid transferase,
      carbonic anhydrase, alpha- and beta-tubulin, dihydropyrimidinase-related protein
      1 and -2, neuronal protein 25, trypsin precursor, glutamate dehydrogenase,
      glutamine synthetase, sorcin, vacuolar ATPase, creatine kinase, albumin and
      guanine nucleotide binding protein beta subunit. All but three of these proteins
      have previously been associated with the major psychiatric disorders. These
      findings provide support for the view that cytoskeletal and mitochondrial
      dysfunction are important components of the neuropathology of the major
      psychiatric disorders.

PMID- 16637011
TI  - Identification of candidate antigen in Whipple's disease using a serological
      proteomic approach.
AB  - Whipple's disease (WD) is a chronic multisystemic infection, caused by Tropheryma
      whipplei, a Gram-positive rod. Recently, a reliable method has been developed for
      cultivating T. whipplei in vitro. This together with the availability of complete
      genome sequence of T. whipplei prompted us to initiate proteome analysis of T.
      whipplei. The objective of the present study was to identify candidate proteins
      for serological diagnosis of WD. Immunoreactivities of sera collected from 18
      patients with WD were compared with those of 24 control subjects who did not have
      WD. For this, we used 2-DE, immunoblotting, and MS. In total, we identified 23
      candidate antigenic proteins. These included a subset of six proteins, each of
      which was found significantly more frequently in cases as compared to their
      controls. The remaining 17 proteins were found exclusively in cases. The methods
      we used in the current study enabled us to identify candidate antigens that, in
      our view, might be useful for serological diagnosis of WD.

PMID- 16637012
TI  - Proteome analysis of rice uppermost internodes at the milky stage.
AB  - Uppermost internodes, which connect the part between the ear and lower stem, form
      an important pathway transporting mineral nutrition from roots and photosynthates
      from leaves (especially the flag leaf) to the ear. The milky stage is the first
      stage of seed ripening. The uppermost internodes of rice at the milky stage are
      critical for seed quality and yield. Total soluble proteins of the uppermost
      internodes of rice (Oryza sativa L. ssp. indica) at the milky stage were analyzed
      using proteomic methods. Using 2-DE, 762 reproducible protein spots were
      detected. Among them, 132 abundant proteins were analyzed using MALDI-TOF-MS.
      Searching in the National Center for Biotechnology Information database, we could
      identify 98 proteins, which represent 80 gene products. These proteins belong to
      11 functional groups with energy production-associated proteins in the first
      place. The large accumulation of proteins involved in metabolism, signaling, and
      stress resistance indicated that the uppermost internodes of rice have a high
      physiological and stress-resistant activity. In addition, our results will also
      enrich the database of the rice proteome.

PMID- 16637013
TI  - Possible dysregulation of chaperon and metabolic proteins in cystic fibrosis
      bronchial tissue.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease due to mutations of the CF
      transmembrane conductance regulator gene. A systematic approach to generate a
      protein expressional pattern in CF bronchial tissue has not been performed so
      far. It was the aim of this hypothesis-generating study to construct differential
      proteomes of bronchial biopsies in controls (n = 8) and CF patients (n = 9).
      Biopsies (pools of three per patient) were taken; proteins were extracted and run
      on 2-DE with subsequent in-gel digestion and mass spectrometrical identification
      and quantification of proteins using specific software. Three hundred sixty-six
      protein spots were identified and compared between groups. Following an approach
      for multiple testing correction, the chaperone 75 kDa glucose-regulated protein
      and ubiquinol-cytochrome c reductase complex core protein I and one form of
      nidogen, a pseudogene of aconitase 2, were increased in CF (p < 0.005). Aberrant
      protein levels may reflect molecular changes of CF as well as CF-linked
      inflammation, infection and cellular stress response.

PMID- 16637014
TI  - Thermostable trypsin conjugates for high-throughput proteomics: synthesis and
      performance evaluation.
AB  - Conjugating bovine trypsin with oligosaccharides maltotriose, raffinose and
      stachyose increased its thermostability and suppressed autolysis, without
      affecting its cleavage specificity. These conjugates accelerated the digestion of
      protein substrates both in solution and in gel, compared to commonly used
      unmodified and methylated trypsins.

PMID- 16637015
TI  - Identification of breast cancer metastasis-associated proteins in an isogenic
      tumor metastasis model using two-dimensional gel electrophoresis and liquid
      chromatography-ion trap-mass spectrometry.
AB  - To better understand the molecular mechanisms underlying breast cancer metastasis
      and search for potential markers for metastatic progression, we have developed a
      highly metastatic variant of human MDA-MB-435 breast cancer cell line through in
      vivo stepwise selection of pulmonary metastatic cells caused by parental MDA-MB
      435 cells in the athymic mice. Comparative proteomic analysis using 2-DE and LC
      IT-MS revealed that 102 protein spots were reproducibly altered more than three
      fold between the selected variant and its parental counterpart. Eleven
      differentially expressed protein spots were identified with high confidence using
      SEQUEST with uninterpreted tandem mass raw data. Cathepsin D precursor,
      peroxiredoxin 6 (PDX6), heat shock protein 27 (HSP27), HSP60, tropomyosin 1
      (TPM1), TPM2, TPM3, TPM4, 14-3-3 protein epsilon, and tumor protein D54 were up
      regulated in the highly metastatic variant, whereas alpha B-crystalline (CRAB)
      was only detected in its parental counterpart. Differential expression was
      confirmed for four proteins including PDX6, CRAB, TPM4, and HSP60 by real-time
      quantitative PCR and Western blotting analysis in our model. Immunohistochemical
      analysis in 80 breast cancer donors demonstrated a significant association of
      TPM4 (p = 0.002), HSP60 (p = 0.001), PDX6 (p = 0.002) but not CRAB (p = 0.113)
      staining with the presence of lymph node metastasis. In addition, TPM4 staining
      was also associated with clinical stage (p = 0.000), but no significant
      association was found between TPM4, PDX6, CRAB, and HSP60 expression and tumor
      size, hormone receptor, and HER-2 status (p > 0.05). The functional implication
      of these identified proteins was also discussed. These proteomic data are
      valuable and informative for understanding breast cancer metastasis and searching
      for potential markers for metastatic progression.

PMID- 16637016
TI  - Recent applications of capillary electrophoresis-electrospray ionisation-mass
      spectrometry in drug analysis.
AB  - This review considers applications in 2004-2005 of capillary electrophoresis
      electrospray ionisation-mass spectrometry (CE-ESI-MS) to the detection and
      determination of small molecular mass drug molecules, taken from the Web of
      Knowledge database. The molecules of small molecular mass less than 1000 Da are
      chosen according to selected structural classes in which they give ESI signals
      primarily as [M + H](+) ions. These structural classes are drugs with amine
      containing side chains, drugs with N-containing saturated ring structures, 1,4
      benzodiazepines, other heterocyclic hypnotics, steroids, bioactive compounds
      containing phenolic groups, and miscellaneous molecules. Details are given on the
      fragmentations, where available, that these ionic species exhibit in-source and
      in ion-trap, triple quadrupole and time-of flight mass spectrometers. The review
      then gives a critical evaluation of these recent CE-ESI-MS analytical methods for
      the detection and determination of these small molecular mass drug molecules.
      Analytical information on, for example, sample concentration techniques, CE
      separation conditions, recoveries from biological media and limits of detection
      are provided.

PMID- 16637017
TI  - Toward high sequence coverage of proteins in human breast cancer cells using on
      line monolith-based HPLC-ESI-TOF MS compared to CE MS.
AB  - A method is developed toward high sequence coverage of proteins isolated from
      human breast cancer MCF10 cell lines using a 2-D liquid separations. Monolithic
      capillary columns prepared by copolymerizing styrene with divinylbenzene are used
      to achieve high-resolution separation of peptides from protein digests. This
      separation is performed with minimal sample preparation directly from the 2-D
      liquid fractionation of the cell lysate. The monolithic column separation is
      directly interfaced to ESI-TOF MS to obtain a peptide map. The protein digests
      were also analyzed by MALDI-TOF MS and an accurate M(r) of the intact protein was
      obtained using an HPLC-ESI-TOF MS. The result is that these techniques provide
      complementary information where nearly complete sequence coverage of the protein
      is obtained and can be compared to the experimental M(r) value. The high sequence
      coverage provides information on isoforms and other post-translational
      modifications that would not be available from methods that result in low
      sequence coverage. The results from the use of monolithic columns are compared to
      that obtained by CE-MS. The monolithic column separations provide a rugged and
      highly reproducible method for separating protein digests prior to MS analysis
      and is suited to confidently identify biomarkers associated with cancer
      progression.

PMID- 16637018
TI  - Restriction landmark genome scanning method using isoschizomers (MspI/HpaII) for
      DNA methylation analysis.
AB  - Restriction landmark genome scanning (RLGS) is a 2-DE of genomic DNA, which
      visualizes thousands of loci. In a conventional RLGS method for methylation
      analysis, we have used a methylation sensitive restriction enzyme, NotI as a
      landmark. However, it was unable to discriminate methylation polymorphism from
      sequence polymorphism. Here, we report an improved RLGS method to detect
      methylated sites directly. We employed isoschizomers, MspI and HpaII, that
      recognize the same sequence (CCGG) but have different methylation sensitivity. We
      carried out the RLGS analysis of Arabidopsis thaliana ecotype Columbia, and
      obtained a pair of spot patterns with MspI and HpaII. We detected 22 spots in
      both patterns. In comparison of them, 18% of the spots were polymorphic, which
      indicated the methylation of C(5m)CGG sites. Further analyses revealed an
      additional methylated site of NotI. Moreover, 52 and 54 restriction enzyme sites
      were also analyzed in two other ecotypes, Wassilewskija and Landsberg erecta,
      respectively. Consequently, 15% of the 52 common sites showed methylation
      polymorphism among the three ecotypes. The restriction sites analyzed in this
      study were located in or near genes, and contribute new data about the
      correlation between methylation status and gene expression. Therefore, this
      result strongly indicates that the improved RLGS method is readily applicable to
      practical analyses of methylation dynamics, and provides clues to the
      relationship between methylation and gene expression.

PMID- 16637019
TI  - Analysis of choline and atropine in hairy root cultures of Cannabis sativa L. by
      capillary electrophoresis-electrospray mass spectrometry.
AB  - We describe a capillary zone electrophoresis method coupled to electrospray
      ionization (ion trap) mass spectrometry (CZE-ESI-MS) for the identification and
      determination of choline and atropine compounds in hairy root extracts from
      Cannabis sativa L. Fused-silica capillary and an alkaline solution of 20 mM
      ammonium acetate at pH 8.5 are used being the most suitable for the analysis of
      choline and atropine in less than 10 min. Under the optimized conditions,
      including CE and ESI-MS parameters, the method resolved both compounds with very
      high sensitivity. The system exhibited good linear response in the range of 25
      500 mg/L and 500-1000 microg/L for choline and atropine, respectively. The
      detection limit of choline was 18 mg/L and 320 microg/L for atropine. Finally,
      the developed method was applied to the analysis of these compounds in transgenic
      root cultures of Cannabis sativa L.

PMID- 16637020
TI  - Determination of tobacco-specific N-nitrosamines in rabbit serum by capillary
      zone electrophoresis and capillary electrophoresis-electrospray ionization-mass
      spectrometry with solid-phase extraction.
AB  - In this paper, we propose a new strategy for separation and determination of
      tobacco-specific N-nitrosamines (TSNAs), a group of strong carcinogens found only
      in tobacco products, by using CZE and CE-MS associated with SPE. Six TSNAs: N'
      nitrosonornicotine, N'-nitrosoanatabine, N'-nitrosoanabasine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanol, and 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol were simultaneously
      separated by either of two CZE methods, one of which worked with ammonium formate
      buffer (pH 2.5) and another with citrate buffer (pH 2.4), as well as a CE-MS
      method. The CZE conditions including pH and concentration of running buffer,
      capillary length, applied voltage, and capillary temperature were systematically
      optimized. For CE-MS method, an optimized sheath liquid consisted of methanol
      water was used at a flow rate of 10 muL/min. With SPE procedure, our proposed CE
      MS method was successfully applied to determine TSNAs after 15 min metabolism in
      rabbits. A comparison study between CZE and CE-MS methods for quantitative
      purposes was carried out, showing that both methods provided similar separation
      efficiency, selectivity, repeatability, linearity, and recovery. However, CE-MS
      method was better suited for the analysis of TSNAs in complicated biological
      samples for its sensitivity and extra information on molecular structure. Having
      good accordance with our previous work by using LC-MS, the new CE-MS method is
      expected to be an alternative to the LC-MS method and applied to study the
      metabolism of TSNAs.

PMID- 16637021
TI  - Altered thymocyte migration during experimental acute Trypanosoma cruzi
      infection: combined role of fibronectin and the chemokines CXCL12 and CCL4.
AB  - We previously showed migration disturbances in the thymus during experimental
      infection with Trypanosoma cruzi, the causative agent of Chagas disease. These
      changes were related to the enhanced expression of extracellular matrix ligands
      and receptors, leading to the escape of immature cells to the periphery. Here, we
      analyzed the expression and role of selected chemokines (CXCL12 and CCL4) and
      their receptors (CXCR4 and CCR5) in regulating thymocyte migration in conjunction
      with extracellular matrix during acute T. cruzi infection. We found increased
      chemokine deposition in the thymus of infected mice when compared to controls,
      accompanied by enhanced co-localization with fibronectin as well as up-regulated
      surface expression of CXCR4 and CCR5 in thymocytes. We also noticed altered
      thymocyte migration towards the chemokines analyzed. Such an enhancement was even
      more prominent when fibronectin was added as a haptotatic stimulus in combination
      with a given chemokine. Our findings suggest that thymocyte migration results
      from a combined action of chemokines and extracellular matrix (ECM), which can be
      altered during pathological conditions such as T. cruzi infection, and may be at
      the origin of the changes in the T cell repertoire seen in this pathological
      process.

PMID- 16637023
TI  - Changes in motor subtype and risk for incident dementia in Parkinson's disease.
AB  - The objective of this study was to assess the temporal relationship between
      changes in predominant motor symptoms and incident dementia in Parkinson's
      disease (PD). A community-based sample of 171 nondemented patients with PD was
      followed prospectively and examined at baseline and after 4 and 8 years. The
      motor subtype of Parkinsonism was classified into tremor-dominant (TD),
      indeterminate, or postural instability gait difficulty (PIGD) subtype at each
      visit, based on defined items in the Unified Parkinson's Disease Rating Scale,
      subscales II and III. Dementia was diagnosed according to DSM-III-R criteria,
      based on clinical interview, cognitive rating scales, and neuropsychological
      examination. Logistic regression was used to analyze the relationship between
      subtype of Parkinsonism and dementia. Transition from TD to PIGD subtype was
      associated with a more than threefold increase in the rate of Mini-Mental State
      Examination decline. Compared to patients with persistent TD or indeterminate
      subtype, the odds ratio for dementia was 56.7 (95% CI: 4.0-808.4; P = 0.003) for
      patients changing from TD or indeterminate subtype to PIGD subtype, and 80.0 (95%
      CI: 4.6-1400.1; P = 0.003) for patients with persistent PIGD subtype. Patients
      with TD subtype at baseline did not become demented until they developed PIGD
      subtype, and dementia did not occur among patients with persistent TD subtype of
      Parkinsonism. In a substantial proportion of PD patients who develop postural
      instability and gait disorder during the course of the disease, this transition
      is associated with accelerated cognitive decline and highly increased risk for
      subsequent dementia. These findings raise the question whether PIGD and dementia
      share common or parallel neuropathology.

PMID- 16637024
TI  - Punding and computer addiction in Parkinson's disease.
AB  - Punding is a stereotypical behavior in which there is an intense fascination with
      repetitive handling and examining of mechanical objects, such as taking apart
      watches and radios or arranging common objects (lining up pebbles, rocks, or
      other small objects). This disabling condition, different from both obsessive
      compulsive disorder and mania, is probably underreported. Punding is thought to
      be related to dopaminergic stimulation, although only a few observations of this
      condition in patients with Parkinson's disease (PD) under therapy has been
      reported. We report a man with PD who developed an unusual, severe, repetitive
      behavior characterized by spending most of his time on his computer; this
      abnormal behavior was concomitant with the introduction of L-dopa (400 mg per
      day) and was not associated to a pattern of chronic inappropriate overuse of
      dopaminergic medication or other psychiatric symptoms. The patient had the
      feeling he was forced into a disruptive and unproductive behavior, and he made
      several attempts to quit without succeeding.

PMID- 16637025
TI  - Biomechanical evaluation of the interfacial strength of a chemically modified
      sandblasted and acid-etched titanium surface.
AB  - The functional capacity of osseointegrated dental implants to bear load is
      largely dependent on the quality of the interface between the bone and implant.
      Sandblasted and acid-etched (SLA) surfaces have been previously shown to enhance
      bone apposition. In this study, the SLA has been compared with a chemically
      modified SLA (modSLA) surface. The increased wettability of the modSLA surface in
      a protein solution was verified by dynamic contact angle analysis. Using a well
      established animal model with a split-mouth experimental design, implant removal
      torque testing was performed to determine the biomechanical properties of the
      bone-implant interface. All implants had an identical cylindrical shape with a
      standard thread configuration. Removal torque testing was performed after 2, 4,
      and 8 weeks of bone healing (n = 9 animals per healing period, three implants per
      surface type per animal) to evaluate the interfacial shear strength of each
      surface type. Results showed that the modSLA surface was more effective in
      enhancing the interfacial shear strength of implants in comparison with the
      conventional SLA surface during early stages of bone healing. Removal torque
      values of the modSLA-surfaced implants were 8-21% higher than those of the SLA
      implants (p = 0.003). The mean removal torque values for the modSLA implants were
      1.485 N m at 2 weeks, 1.709 N m at 4 weeks, and 1.345 N m at 8 weeks; and
      correspondingly, 1.231 N m, 1.585 N m, and 1.143 N m for the SLA implants. The
      bone-implant interfacial stiffness calculated from the torque-rotation curve was
      on average 9-14% higher for the modSLA implants when compared with the SLA
      implants (p = 0.038). It can be concluded that the modSLA surface achieves a
      better bone anchorage during early stages of bone healing than the SLA surface;
      chemical modification of the standard SLA surface likely enhances bone apposition
      and this has a beneficial effect on the interfacial shear strength.

PMID- 16637026
TI  - Comparison of conventional and highly crosslinked UHMWPE patellae evaluated by a
      new in vitro patellofemoral joint simulator.
AB  - A series of in vitro patella damage tests were developed using a knee simulator
      to investigate electron-beam-irradiated and -melted ultra-high molecular weight
      polyethylene and conventional ultra-high molecular weight polyethylene at the
      patellofemoral articulation. Three different simulations were created: (i) normal
      gait with optimal component alignment, (ii) stair climbing with optimal component
      alignment, and (iii) stair climbing with 4 degrees of femoral component internal
      rotation to simulate a component malalignment condition. In the last two
      simulations, all patellae were artificially aged. In normal gait, the unaged
      conventional and highly crosslinked patellae demonstrated similar behavior. In
      both stair climbing tests, unlike the aged highly crosslinked components, the
      aged conventional patellae developed cracks by 2 million cycles. These results
      demonstrate the potential advantage of highly crosslinked polyethylene for the
      patella.

PMID- 16637027
TI  - Multiphoton excited fabricated nano and micro patterned extracellular matrix
      proteins direct cellular morphology.
AB  - We use multiphoton excited (MPE) photochemistry to fabricate patterned
      extracellular matrices (ECM) and to investigate the morphology of human dermal
      fibroblasts adhered to the resulting photocrosslinked linear structures of
      fibronectin (FN), fibrinogen (FG), and bovine serum albumin (BSA). These proteins
      were chosen to systematically investigate the roles of topography and ECM
      biochemistry on cell spreading, as fibroblasts bind directly to both FN and FG at
      RGD sites through known integrins, whereas BSA provides no comparable ECM cues
      for cell binding. MPE crosslinked patterns are created from parallel linear
      structures 600 nm in width, 200 microm in length, and spaced by either 10 or 40
      microm. Immunofluorescence staining of FN and FG was used to assay the
      functionality of crosslinked proteins. The metrics of orientation, elongation,
      and cell perimeter were used to quantitate the resulting cellular behavior on the
      crosslinked protein patterns. These parameters all reflect statistical
      differences for cells on BSA, relative to the similar statistical behavior on
      fibronectin and fibrinogen. Cells on the BSA patterns are constrained by physical
      guidance and orientation between linear structures. In contrast, cells adhered on
      both FN and FG had a greater propensity to spread across adjacent structures,
      indicating the importance of cell matrix interactions. Focal adhesion staining of
      cells adhered to the protein structures revealed similar trends. These findings
      are consistent with our hypothesis that these crosslinked matrix protein
      structures are expected to direct cell adhesion and spreading and that the
      topography and ECM cues lead to different forms of guidance.

PMID- 16637028
TI  - Intra-articular calcium phosphate cement: Its fate and impact on joint tissues in
      a rabbit model.
AB  - Clinical application of injectable ceramic cement in comminuted fractures
      revealed penetration of the viscous paste into the joint space. Not much is known
      on the fate of this cement and its influence on articular tissues. The purpose of
      this experimental study was to assess these unknown alterations of joint tissues
      after intra-articular injection of cement in a rabbit knee. Observation periods
      were from 1 week up to 24 months, with three rabbits per group. Norian SRS cement
      was injected into one knee joint, the contralateral side receiving the same
      volume of Ringers' solution. Light microscopic evaluation of histologic sections
      was performed, investigating the appearance of the cement, inflammatory
      reactions, and degenerative changes of the articular surface. No signs of
      pronounced acute or chronic inflammation were visible. The injected cement was
      mainly found as a single particle, anterior to the cruciate ligaments. It became
      surrounded by synovial tissues within 4 weeks and showed signs of superficial
      resorption. In some specimens, bone formation was seen around the cement.
      Degeneration of the articular surface showed no differences between experimental
      and control side, and no changes over time became apparent. No major degenerative
      changes were induced by the injected cement. The prolonged presence of cement
      still seems to make it advisable to remove radiologically visible amounts from
      the joint space.

PMID- 16637029
TI  - Use of polylactic acid/polytrimethylene carbonate blends membrane to prevent
      postoperative adhesions.
AB  - The objective of the study was to evaluate the effect of a novel biodegradable
      membrane on the prevention of postoperative adhesion formation. The membrane was
      prepared by blending 50% PLA (polylactic acid) with 50% PTMC (polytrimethylene
      carbonate). The prepared blends polymer membrane was more flexible than pure PLA
      membrane, as measured by glass-transition temperature and tensile study.
      Cytotoxicity study revealed that PLA/PTMC blends membrane showed good
      biocompatibility. The membrane elicited slight tissue reaction based on the
      results of histological study. Thirty adult Japanese rabbits were used for the
      intestine adhesion model. The treatment group had PLA/PTMC membrane, the control
      group had chitosan, and the blank control group was not operated. The animals
      were housed for two weeks and sacrificed to investigate adhesion of intestine.
      Compared with the blank control group, the treatment group and the control group
      lowered the extent of adhesions (p < 0.01), but the treatment group was better
      than the control group (p < 0.05). The in-vivo studies confirmed that PLA/PTMC
      blends membrane could prevent postoperative adhesions.

PMID- 16637030
TI  - Determination of the force necessary for the propagation of tears in ostrich and
      calf pericardium.
AB  - The durability of prosthetic heart valve leaflets made of biological materials is
      limited. A tear in the biomaterial accelerates their early failure, but
      microtearing of the collagen fibers may be responsible for their medium-term
      failure. We studied the force necessary to propagate tearing in two biomaterials:
      ostrich and calf pericardium. One hundred twenty samples of each tissue were
      tested in an Elmendorf pendulum capable of measuring the force required to tear a
      tissue in which a predefined slit had been made. The forces required to produce
      tears, ranging between 2.5 and 0.25 cm in length, were determined. For ostrich
      pericardium, this force ranged between 67.67 and 4.80 newton, while that required
      to tear the same lengths of calf pericardium ranged between 70.67 and 4.70
      newton. The function that relates the tearing force to the length of the tear was
      expressed as follows: y = 20.62x + 1.77x(2) (R(2) = 0.923) for ostrich
      pericardium and y = 45.57x - 7.21x(2) (R(2) = 0.936) for calf pericardium, where
      y is the force in newton and x is the length in centimeter. Calf pericardium was
      found to have a greater resistance to tearing. However, these results should be
      interpreted with caution owing to the fact that the thickness of the majority of
      the samples of ostrich pericardium was significantly less than that of calf
      pericardium. A more careful selection and utilization of adult ostrich
      pericardium would probably improve these results.

PMID- 16637031
TI  - Ionic liquid-derived blood-compatible composite membranes for kidney dialysis.
AB  - A novel heparin- and cellulose-based biocomposite is fabricated by exploiting the
      enhanced dissolution of polysaccharides in room temperature ionic liquids
      (RTILs). This represents the first reported example of using a new class of
      solvents, RTILs, to fabricate blood-compatible biomaterials. Using this approach,
      it is possible to fabricate the biomaterials in any form, such as films or
      membranes, fibers (nanometer- or micron-sized), spheres (nanometer- or micron
      sized), or any shape using templates. In this work, we have evaluated a membrane
      film of this composite. Surface morphological studies on this biocomposite film
      showed the uniformly distributed presence of heparin throughout the cellulose
      matrix. Activated partial thromboplastin time and thromboelastography demonstrate
      that this composite is superior to other existing heparinized biomaterials in
      preventing clot formation in human blood plasma and in human whole blood.
      Membranes made of these composites allow the passage of urea while retaining
      albumin, representing a promising blood-compatible biomaterial for renal
      dialysis, with a possibility of eliminating the systemic administration of
      heparin to the patients undergoing renal dialysis.

PMID- 16637032
TI  - Adhesion of composite to enamel and dentin surfaces irradiated by IR laser pulses
      of 0.5-35 micros duration.
AB  - The characteristics of laser-treated tooth surfaces depend on the laser
      wavelength, pulse duration, spatial and temporal laser beam quality, incident
      fluence, surface roughness, and the presence of water during irradiation. Ablated
      surfaces are most commonly restored with adhesive dental materials and the
      characteristics of the ablated surfaces influence adhesion of restorative
      materials. Previous studies suggest that high bond strengths can be achieved
      using shorter laser pulses that minimize peripheral thermal damage. In this
      study, Er:YSGG, Er:YAG, and CO(2) lasers were used at irradiation intensities
      sufficient to simulate efficient clinical caries removal to uniformly irradiate
      bovine enamel and human dentin surfaces using a motion control system with a
      microprocessor-controlled water spray. The degree of spatial overlap of adjacent
      pulses was varied so as to investigate the influence of irradiation uniformity
      and surface roughness on the bond strength. Composite resin was bonded to the
      irradiated surfaces and shear bond tests were used to obtain bond strengths in
      MPa. The highest results were obtained using the Er:YAG pulses with pulse
      durations less than 35 mus without the necessity for postirradiation acid
      etching. Some of these groups were not significantly different from
      nonirradiated, acid-etch-only positive control groups.

PMID- 16637033
TI  - Water absorption characteristics of novel Cu/LDPE nanocomposite for use in
      intrauterine devices.
AB  - Intrauterine devices (IUDs), especially the copper-containing IUDs (Cu-IUDs), are
      one of the worldwide used forms for birth control, owing to their advantages of
      long-lasting and high efficacy, economy, safety, and reversibility. However, it
      is not perfect for the existing Cu-IUDs; some shortcomings related to its side
      effects have not been overcome yet. For this reason, a new Cu-IUDs material, the
      copper/low-density polyethylene (Cu/LDPE) nanocomposite, has been developed in
      our research team. The structure and water uptake characteristics of this new Cu
      IUDs material have been investigated by using X-ray diffraction (XRD), Scanning
      electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS), Fourier
      transform infrared spectroscopy (FT-IR), and gravimetric analysis in this paper.
      The results of XRD, SEM, EDS, and FT-IR show three important outcomes associated
      with the structure of the nanocomposite. First, the nanocomposite is hybrid of
      the polymer and the copper nanoparticles (nano-Cu). Second, porosities, nano-Cu
      aggregates, and primary alcohol (R--CH(2)--OH) are existed in the nanocomposite.
      Third, the nano-Cu aggregates are distributed uniformly in the polymer matrix in
      general. The results of Gravimetric analysis, which associated with the water
      uptake characteristics of the nanocomposite, exhibit that the water absorption
      behavior of the nanocomposite obeys the classical diffusion theory very well, the
      water uptake of the nanocomposite increases with the increasing of the nano-Cu
      loading, and that the water uptake ability of the nanocomposite with 15.0 wt %
      nano-Cu (50 nm in diameter) is about 150 times larger than that of the base resin
      and about 45 times higher than that of the Cu/LDPE microcomposite with 15.0 wt %
      copper microparticles (5 microm in diameter). These water uptake characteristics
      are mainly attributed to the structure of the Cu/LDPE composites and the size
      effect of the nano-Cu.

PMID- 16637035
TI  - Effects of two multi-step self-etch primer/adhesives on apoptosis in human
      gingival fibroblasts in vitro.
AB  - Various in vitro studies have shown induction of apoptosis by monomers
      incorporated to dental restorative materials and adhesive resins, while
      information regarding the effect of monomer combinations as commercially
      available products on apoptosis is limited. The aim of this study was to
      investigate the effects of two multi-step self-etch primer/adhesive systems on
      apoptosis of cultured primary human gingival fibroblasts. Cells were treated up
      to 48 h with Clearfil SE Bond (Kuraray, Japan) and FL Bond (Shofu, Japan) at
      1:1000 v:v ratio to determine cell proliferation, using 0.02 mM staurosporine as
      positive control. Apoptosis was assessed using propidium iodide/acridine orange
      (PI/AO) staining, compared to nontreated controls. When compared to FL Bond,
      exposure of gingival fibroblasts to Clearfil SE Primer and Clearfil SE Bond
      resulted in a higher degree of cell proliferation. PI/AO staining revealed
      typical morphological features of apoptosis in FL Bond and Staurosporine groups,
      while some cells cultured in the presence of primer and adhesive components of
      Clearfil SE Bond showed nuclear fragmentation, indicative of early apoptosis. Our
      results indicate that apoptotic potential of the multi-step self-etch adhesives
      were material-dependent within the 48 h test period.

PMID- 16637036
TI  - Effect of high light intensity on cavity wall adaptation of a resin composite
      with a self-etching primer system.
AB  - This study evaluated the effect of high light intensity using a plasma arc lamp
      on the cavity wall adaptation of photo-polymerized composite restorations. Bowl
      shaped cavities were prepared on the labial surfaces of extracted bovine teeth.
      Each cavity was restored with a resin composite restorative system (SE Bond &
      Clearfil AP-X) and then polymerized using a plasma arc lamp (Arc Light II) with a
      series of light intensities, including 1100, 1200, 1300, 1400, 1500, and 1600
      mW/cm(2), and a halogen lamp (Candilux) with 400 mW/cm(2) light intensity (n =
      10). The photo-irradiation time was adjusted for each group to receive a total
      energy output of approximately 16,000 mJ/cm(2). The specimens were subjected to
      2500 cycles of thermal fatigue and sectioned bucco-lingually through the center
      of the restoration. Contraction gaps on the sections were measured using a
      replica-SEM observation technique. The degree of gap formation was determined as
      the ratio of the total length of the contraction gaps to the total length of the
      cavity wall on each sectioned specimen. The value was converted to a percentage.
      The data were statistically analyzed with Kruskal-Wallis and Mann-Whitney U tests
      at a 0.05 level of significance. There were no significant differences (p > 0.05)
      in the cavity adaptation among the composites polymerized by the plasma arc lamp
      with high light intensities and the composite polymerized with the halogen lamp
      with 400 mW/cm(2) light intensity. There were no significant differences (p >
      0.05) in the degree of cavity adaptation among the specimens polymerized with
      light intensities higher than 1100 mW/cm(2).

PMID- 16637034
TI  - An instrumented scaffold can monitor loading in the knee joint.
AB  - No technique has been consistently successful in the repair of large focal
      defects in cartilage, particularly in older patients. Tissue-engineered cartilage
      grown on synthetic scaffolds with appropriate mechanical properties will provide
      an implant, which could be used to treat this problem. A means of monitoring
      loads and pressures acting on cartilage, at the defect site, will provide
      information needed to understand integration and survival of engineered tissues.
      It will also provide a means of evaluating rehabilitation protocols. A "sensate"
      scaffold with calibrated strain sensors attached to its surface, combined with a
      subminiature radio transmitter, was developed and utilized to measure loads and
      pressures during gait. In an animal study utilizing six dogs, peak loads of 120N
      and peak pressures of 11 MPa were measured during relaxed gait. Ingrowth into the
      scaffold characterized after 6 months in vivo indicated that it was well anchored
      and bone formation was continuing. Cartilage tissue formation was noted at the
      edges of the defect at the joint-scaffold interfaces. This suggested that native
      cartilage integration in future formulations of this scaffold configured with
      engineered cartilage will be a possibility.

PMID- 16637037
TI  - Levetiracetam in tardive dyskinesia: an open label study.
AB  - Levetiracetam (LEV), a novel antiepileptic drug, has demonstrated antidyskinetic
      effect in preclinical animal models of Parkinson's disease (PD) and in one open
      label study in PD patients with levodopa-induced dyskinesia. The acute
      antidyskinetic effects of LEV in patients with tardive dyskinesia were evaluated
      in an open label study. Eight patients received oral LEV (1,000 mg/day) for 1
      month and blinded evaluations were performed at baseline and at the end of the
      treatment period. A significant reduction of the abnormal movements was recorded
      while psychiatric symptoms did not worsen and the adverse event profile was
      benign. LEV may be efficacious for the treatment of tardive dyskinesia and
      deserves further clinical testing.

PMID- 16637038
TI  - Disappearance of essential tremor after frontal cortical infarct.
AB  - We present a patient with essential tremor who spontaneously improved after a
      sensorimotor stroke related to a small cortical infarct near by the left
      precentral region of the brain. This finding supports the presence of cortical or
      transcortical motor loops that are likely involved in essential tremor and
      suggests a possible link with the cerebellar-thalamic-cortical pathway.

PMID- 16637039
TI  - Randomized study of sertraline and low-dose amitriptyline in patients with
      Parkinson's disease and depression: effect on quality of life.
AB  - We assessed the effect of 3-month treatment of sertraline (50 mg) or low-dose
      amitriptyline (25 mg) on depression and quality of life in 31 patients with
      Parkinson's disease in a prospective single-blind randomized study. Both drugs
      significantly reduced the Hamilton Depression Rating Scale (HDRS-17) score.
      Completion rate was 75% for sertraline (12 of 16) and 73% for amitriptyline (11
      of 15). Responder rate (HDRS-17 score reduction >/= 50%) was 83.3% for sertraline
      and 72.7% for amitriptyline. Sertraline but not amitriptyline treatment
      determined a significant benefit on quality of life (PDQ-39 scale). We found no
      change in Unified Parkinson's Disease Rating Scale scores. However, the
      improvement in specific PDQ-39 subscores (mobility, activities of daily living,
      and stigma) suggests that depression affects patient self-perception of motor
      function and further emphasizes the need for its treatment.

PMID- 16637040
TI  - End of day dyskinesia in advanced Parkinson's disease can be eliminated by
      bilateral subthalamic nucleus or globus pallidus deep brain stimulation.
AB  - We report the therapeutic effects of deep brain stimulation (DBS) in 2 patients
      with Parkinson's disease (PD) with severe end of dose dyskinesia that was
      resistant to medical therapy. In both patients, severe, end of day ballistic
      dyskinesias occurred when the last levodopa dose of the day was wearing off.
      Globus pallidus (GPi) DBS in 1 case and subthalamic (STN) DBS in the second case
      produced full resolution of end of day dyskinesia.

PMID- 16637041
TI  - In vitro bioactivity and osteoblast response of porous NiTi synthesized by SHS
      using nanocrystalline Ni-Ti reaction agent.
AB  - Porous NiTi with an average porosity of 55 vol % and a general pore size of 100
      600 microm was synthesized by self-propagating high temperature synthesis (SHS)
      with the addition of mechanically alloyed nanocrystalline Ni-Ti as the reaction
      agent. The SHS of porous NiTi using elemental powders was also performed for
      comparison. To enhance the bioactivity of the metal surface, porous NiTi
      synthesized by nanocrystalline Ni-Ti was subjected to chemical treatment to form
      a layer of TiO(2) coating. The porous NiTi with TiO(2) coating was subsequently
      immersed in a simulated body fluid (SBF) to investigate its apatite forming
      ability. The effects of the addition of nanocrystalline Ni-Ti as reaction agent
      and the application of apatite coating on osteoblastic behavior were studied in
      primary cultures of human osteoblast cells. Results showed that the main phases
      in porous NiTi synthesized by elemental powders were NiTi, Ti(2)Ni, and unreacted
      free Ni. By using nanocrystalline Ni-Ti as reaction agent, the secondary
      intermetallic phase of Ti(2)Ni was significantly reduced and the free Ni was
      eliminated. TiO(2) coating with anatase phase was formed on the surface of porous
      NiTi after the chemical treatment. A layer consisting of nanocrystalline
      carbonate-containing apatite was formed on the surface of TiO(2) coating after
      soaking in SBF. The preliminary cell culture studies showed that the porous NiTi
      synthesized with the addition of nanocrystalline Ni-Ti attracted marked
      attachment and proliferation of the osteoblast cells. This gives the evidence of
      the potential biomedical applications of the porous NiTi.

PMID- 16637042
TI  - Porous silk fibroin 3-D scaffolds for delivery of bone morphogenetic protein-2 in
      vitro and in vivo.
AB  - Bone morphogenetic protein-2 (BMP-2) plays a key role in osteogenesis.
      Biomaterials used for the sustained delivery of BMP-2 in vivo have shown
      therapeutic benefits. In the present study, BMP-2 was loaded in porous silk
      fibroin scaffolds derived from silkworm cocoons (2.4 +/- 0.14 microg per
      scaffold). The release profile of BMP-2 under dynamic culture conditions (spinner
      flasks) showed that after 1 week in culture 25% of the initial BMP-2 was retained
      adsorbed to the scaffold; up to 4 weeks no additional BMP-2 was released. BMP-2
      induced human bone marrow stromal cells (hMSCs) to undergo osteogenic
      differentiation when the seeded scaffolds were cultured in medium supplemented
      with osteogenic stimulants for 4 weeks, based on elevated alkaline phosphatase
      activity, calcium deposition, and transcript levels for bone sialoprotein,
      osteopontin, osteocalcin, BMP-2, and cbfa-1. Micro-computed tomography revealed
      densely deposited mineral at the center of the scaffolds. In contrast, hMSCs
      cultured in control scaffolds (no BMP-2) exhibited limited osteogenesis. When
      implanted in critical sized cranial defects in mice, scaffolds loaded with BMP-2
      and seeded with hMSCs resulted in significant bone ingrowth. These results were
      qualitatively similar to scaffolds loaded with BMP-2 but no hMSCs or with BMP-2
      and hMSCs but not pregrown into bone-like tissue. Bone-related outcomes were
      improved when compared with the scaffold controls implanted without BMP-2. These
      studies illustrate the potential use of slow degrading silk fibroin 3-D scaffolds
      loaded with BMP-2, in combination with hMSCs, in osteogenesis studies in vitro
      and in vivo, and provide a new range of material properties for these
      applications.

PMID- 16637043
TI  - Macroporous and nanofibrous polymer scaffolds and polymer/bone-like apatite
      composite scaffolds generated by sugar spheres.
AB  - Scaffolds are crucial to tissue engineering/regeneration. In this work, a
      technique combining a unique phase-separation process with a novel sugar sphere
      template leaching process has been developed to produce three-dimensional
      scaffolds. The resulting scaffolds possess high porosities, well connected
      macropores, and nanofibrous pore walls. The technique advantageously controls
      macropore shape and size by sugar spheres, interpore opening size by assembly
      conditions (time and temperature of heat treatment), and pore wall morphology by
      phase-separation parameters. The bioactivity of a macroporous and nanofibrous
      poly(L-lactic acid) (PLLA) scaffold was demonstrated by the bone-like apatite
      deposition throughout the scaffold in a simulated body fluid (SBF).
      Preincorporation of nanosized hydroxyapatite eliminated the induction period and
      facilitated the apatite growth in the SBF. Interestingly, the apatite growth
      primarily occurred on the surface of the pores (internal and external) but not
      the interior of the nanofibrous network away from the pore surface. It was also
      noticed that the macropore size did not affect the apatite growth rate, while the
      interpore opening size did. The compressive modulus also increased substantially
      when a continuous apatite layer was formed on the pore walls of the scaffold. The
      resulting composite scaffold mimics natural bone matrix with the combination of
      an organic phase (a polymer such as PLLA) and an inorganic apatite phase. The
      demonstrated bioactivity of apatite layer, together with well-controlled
      macroporous and nanofibrous structures, makes the novel nanocomposite scaffolds
      desirable for bone tissue engineering.

PMID- 16637044
TI  - Laser-deposited Ti-Nb-Zr-Ta orthopedic alloys.
AB  - The complex quaternary Ti-35Nb-7Zr-5Ta orthopedic alloy has been successfully
      deposited from a powder feedstock consisting of a blend of elemental titanium,
      niobium, zirconium, and tantalum powders, using the laser engineered net-shaping
      (LENStrade mark) process. In the as laser-deposited form, these alloys exhibit a
      substantially higher tensile strength as compared with more conventionally
      processed counterparts of similar composition, while maintaining excellent
      ductility and a low modulus. Furthermore, the as-deposited alloys appear to
      exhibit a <001> texture, with a substantially large number of grains of the beta
      phase aligning one of their <001> axes nearly normal to the substrate or parallel
      to the growth direction. The microstructure of the as-deposited as well as
      tensile-tested alloys have been characterized in detail using scanning electron
      microscopy (SEM), orientation microscopy (OM), and transmission electron
      microscopy (TEM). Formation of a high density of shear bands, possibly arising
      from slip localization due to precipitates of the omega phase in the beta matrix,
      is clearly evident in the tensile-tested sample. The enhanced tensile strength
      and low modulus in these laser-deposited alloys coupled with the ability to form
      near-net shape components makes LENS an attractive processing technology for
      orthopedic implants.

PMID- 16637045
TI  - Cytotoxicity and altered c-myc gene expression by medical polyacrylamide
      hydrogel.
AB  - Medical Polyacrylamide Hydrogel (PAMG)has been used in plastic and aesthetic
      surgery for years. However, its safety is still in doubt in many countries. In
      the current research, first an approach, using high performance liquid
      chromatography (HPLC), to determine the amount of residual acrylamide monomer
      (AM) in the PAMG was presented. Then the cytotoxicity of PAMG was investigated
      using cell counting and methyl thiazolyl tetrazolium (MTT) assay. To explore the
      mechanism of this toxicity, normal human fibroblasts cultured in medium extracts
      were analyzed. Membrane changes and other related parameters were investigated
      using flow cytometry (FCM). Real time fluorescent polymerase chain reaction (real
      time PCR) was also introduced to determine the biological response of the
      fibroblasts. During this process, three representative genes (p53, beta-actin,
      and c-myc, which are tumor suppressor genes, housekeeping genes, and proto
      oncogenes respectively) were selected for examination. Results indicated that a
      method based on HPLC is practical and simple for determining AM in PAMG. The
      detection limits can reach the desired ppb level, and so it can fully meet the
      requirements of the studies of PAMG. Polyacylamide Hydrogel inhibits the growth
      of human fibroblasts and may cause the apoptosis of human fibroblasts. Moreover,
      it can alter physical parameters such as the size and the granularity of these
      cells. Furthermore, these three genes have a relatively typical amplification
      plot and highly related, wide-range standard curves, and so this reaction system
      is definitely suitable for the semiquantification of these genes. PAMG induces
      the increase of the message ribonucleic acid (mRNA) expression of c-myc, while
      the p53 and beta-actin remain even. This change is not related to the
      concentration of AM in the gel and may be incited by other components in the
      extract of PMAG.

PMID- 16637047
TI  - Features associated with excessive exercise in women with eating disorders.
AB  - OBJECTIVE: Excessive exercise and motor restlessness are observed in a
      substantial number of patients with eating disorders. This trait has been studied
      extensively among animal models of activity anorexia nervosa (AN) and may hold
      particular interest as an endophenotype for AN. We explored features associated
      with excessive exercise across subtypes of eating disorders. METHOD: Participants
      were female probands and affected female relatives from the multi-site
      international Price Foundation Genetic Studies with diagnoses of AN, bulimia
      nervosa (BN), and both AN and BN or eating disorder not otherwise specified (ED
      NOS) (N=1,857). Excessive exercise was defined based on responses to the
      Structured Interview for Anorexic and Bulimic Disorders (SIAB). RESULTS: Among
      the eating disorder diagnostic groups, excessive exercise was most common among
      the purging subtype of AN. Individuals who reported excessive exercise also
      reported lower minimum BMI, younger age at interview, higher scores on anxiety,
      perfectionism, and eating disorder symptom measures, more obsessions and
      compulsions, and greater persistence. CONCLUSION: Excessive exercise may be
      associated particularly with the purging subtype of AN as well as with a
      constellation of anxious/obsessional temperament and personality characteristics
      among women with eating disorders.

PMID- 16637048
TI  - Associations between juvenile delinquency and weight-related variables: analyses
      from a national sample of high school students.
AB  - OBJECTIVE: This study examined direct and conditional associations between
      juvenile delinquency and weight-related variables in a national sample of high
      school students. METHOD: Data from the 2003 Youth Risk Behavior Survey (YRBS) of
      12,713 high school students aged 14 to 17 were examined. Logistic regression
      analyses were used to analyze the data. RESULTS: Bivariate and multivariate
      analyses indicated that juvenile delinquents were more likely than nondelinquents
      to use fasting, vomiting, and drugs to lose weight or to keep from gaining
      weight. Multivariate analyses also showed that delinquents were more likely than
      nondelinquents to perceive themselves as overweight, but the two groups did not
      differ in regard to actual overweight status. Tests of interactions in
      multivariate analyses indicated that the associations between delinquent status
      and specific, weight-related variables were stronger among younger than among
      older adolescents, as well as among female than among male adolescents.
      CONCLUSIONS: Future research should examine risk and protective factors for
      unhealthy weight control behaviors and perceptions among delinquents.

PMID- 16637049
TI  - Impact of an exercise program on physical, emotional, and social aspects of
      quality of life of individuals with Parkinson's disease.
AB  - We evaluated changes in different domains of quality of life (QL) for persons
      with Parkinson's disease after a program of physical activity. Twenty subjects
      with a diagnosis of Parkinson's disease classified as Stages 1 to 3 on the Hoehn
      and Yahr scale and with a mean age of 61.5 +/- 9.8 years participated in 36 group
      sessions of a combined group program of aerobic conditioning and muscular
      strengthening. QL was investigated by the Nottingham Health Profile, a generic
      questionnaire composed of six domains. Student's paired t tests indicated
      significant gains associated with the program (P < 0.05) on the total score and
      those related to emotional reactions (ER), social interactions (SI), and physical
      ability (PA). SI was the domain that showed the greatest program gains (41.4%).
      The program of physical activity performed with persons with Parkinson's disease
      at light to moderate stages resulted in improvements in their perception of QL,
      mainly in the domains of ER, SI, and PA.

PMID- 16637050
TI  - Effect of buffer species on the thermally induced aggregation of interferon-tau.
AB  - It is now becoming apparent that a common pathway of protein aggregation involves
      the unimolecular structural rearrangement from the native state to a slightly
      expanded aggregation-competent species. It is the goal of this study to
      understand the aggregation and the effects of buffer on the stability of IFN-tau.
      In this study, the thermally-induced aggregation of interferon-tau (IFN-tau) is
      described. By monitoring the aggregation rate in the presence of increasing
      amounts of sucrose, the relative change in surface area (Deltas) for conversion
      to the aggregation-competent state can be determined. Under conditions of pH 7
      and in 20 mM buffer, the protein displays different aggregation rates depending
      on the nature of the buffer species. The protein aggregates mostly quickly in
      phosphate buffer, slower in the presence of Tris and slowest in the presence of
      histidine. The largest value for Deltas occurs for the histidine-containing
      samples, where aggregation proceeds via a slightly expanded aggregation competent
      state with a surface area increase of 7.6%. Furthermore, it appears that
      histidine binds to the native state of IFN-tau, thereby stabilizing the native
      state and retarding aggregation. Measurement of the second virial coefficient,
      B(22), for different formulations indicates that inclusion of histidine has only
      a small effect on repulsion between protein molecules, suggesting that colloidal
      stabilization is not the dominant mechanism for stabilization of IFN-tau. This
      study represents the first detailed biophysical study of specific buffer-induced
      stabilization, resulting in shifting the equilibrium towards the native state and
      away form the expanded aggregation-competent species.

PMID- 16637051
TI  - Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical and radiological findings
      in sibs homozygous for premature stop codon mutation in the COL11A2 gene.
AB  - Oto-spondylo-megaepiphyseal dysplasia (OSMED) is a very rare disorder due to
      mutation of type XI collagen. Less than 30 patients have been reported in the
      literature so far. It could be either of autosomal dominant (OMIM 154780) or
      recessive (OMIM 215150) etiology. Two sibs with OSMED are presented. They had
      disproportionate short stature and short limbs, distinct face with midface
      hypoplasia, short nose, depressed nasal bridge, long philtrum, and non
      progressive sensorineural deafness. Radiological findings showed short long bones
      and large epiphyses with metaphyseal flaring and mild platyspondyly and coronal
      clefting. Homozygosity of a single nucleotide deletion in exon 55 causing a
      premature stop codon in exon 56 of COL11A2 was detected in the affected sibs.
      Parents were heterozygotes for the same mutation and interestingly, the father
      had mild unilateral non-progressive sensorineural deafness. This finding adds
      more weight that the type of mutation and location in COL11A2 are crucial in
      determining the phenotype. The purpose of this study is to report clinical and
      radiological findings in two molecularly proven Egyptian sibs with autosomal
      recessive OSMED.

PMID- 16637052
TI  - Predicting the behavior of novel sugar carriers for dry powder inhaler
      formulations via the use of a cohesive-adhesive force balance approach.
AB  - The aim of this work was to utilize the recently developed cohesive-adhesive
      balance (CAB) technique for analyzing quantitative AFM measurements to compare
      the relative forces of interaction of micronized salbutamol sulfate particles and
      a selection of specifically grown sugar substrates (beta cyclodextrin, lactose,
      raffinose, trehalose and xylitol). The interfacial behavior was subsequently
      related to the in-vitro delivery performance of these sugars as carrier particles
      in dry powder inhalation (DPI) formulations. The CAB analysis indicated that the
      rank order of adhesion between salbutamol sulfate and the sugars was beta
      cyclodextrin < lactose < trehalose < raffinose < xylitol. The beta cyclodextrin
      was the only substrate with which salbutamol sulfate demonstrated a greater
      cohesive behavior. All other sugars exhibited an adhesive dominance. In-vitro
      deposition performance of the salbutamol sulfate based carrier DPI formulations
      showed that the rank order of the fine particle fraction (FPF) was beta
      cyclodextrin > lactose > raffinose > trehalose > xylitol. A linear correlation
      (R(2) = 0.9572) was observed between the FPF and cohesive-adhesive ratios of the
      AFM force measurements. The observed link between CAB analysis of the interactive
      forces and in-vitro performance of carrier based formulations suggested a
      fundamental understanding of the relative balance of the various forces of
      interaction within a dry powder formulation may provide a critical insight into
      the behavior of these formulations.

PMID- 16637053
TI  - Evaluation of a vaporizing device (Volcano) for the pulmonary administration of
      tetrahydrocannabinol.
AB  - What is currently needed for optimal use of medicinal cannabinoids is a feasible,
      nonsmoked, rapid-onset delivery system. Cannabis "vaporization" is a technique
      aimed at suppressing irritating respiratory toxins by heating cannabis to a
      temperature where active cannabinoid vapors form, but below the point of
      combustion where smoke and associated toxins are produced. The goal of this study
      was to evaluate the performance of the Volcano vaporizer in terms of reproducible
      delivery of the bioactive cannabinoid tetrahydrocannabinol (THC) by using pure
      cannabinoid preparations, so that it could be used in a clinical trial. By
      changing parameters such as temperature setting, type of evaporation sample and
      balloon volume, the vaporization of THC was systematically improved to its
      maximum, while preventing the formation of breakdown products of THC, such as
      cannabinol or delta-8-THC. Inter- and intra-device variability was tested as well
      as relationship between loaded- and delivered dose. It was found that an average
      of about 54% of loaded THC was delivered into the balloon of the vaporizer, in a
      reproducible manner. When the vaporizer was used for clinical administration of
      inhaled THC, it was found that on average 35% of inhaled THC was directly exhaled
      again. Our results show that with the Volcano a safe and effective cannabinoid
      delivery system seems to be available to patients. The final pulmonal uptake of
      THC is comparable to the smoking of cannabis, while avoiding the respiratory
      disadvantages of smoking.

PMID- 16637054
TI  - The application of mechanism-based PK/PD modeling in pharmacodynamic-based dose
      selection of muM17, a surrogate monoclonal antibody for efalizumab.
AB  - muM17 is an anti-mouse CD11a monoclonal antibody (mAb) developed as a surrogate
      molecule for assessing potential reproductive toxicities of efalizumab, an anti
      human CD11a mAb approved for treatment of chronic moderate to severe plaque
      psoriasis. This article shows the use of a mechanism-based PK/PD model for muM17
      to further support the determination of dose equivalency of muM17 in the mouse
      and efalizumab in humans based on CD11a expression on T-lymphocytes (PD).
      Patients in clinical studies received 1 mg/kg/week efalizumab subcutaneously for
      12 weeks. In the mouse model, a single IV dose of 1 or 10 mg/kg or a single SC
      dose of 3, 5, or 10 mg/kg muM17 was administered. Drug concentrations and PD were
      quantitated using ELISA and flow cytometry (FACS) analyses, respectively. The
      PK/PD model of muM17 in mice was developed and was validated using sparse data
      from a separate multiple dose PK/PD study. The model was next used to simulate PD
      profiles with multiple dosing regimens mimicking those of the clinical dose of
      efalizumab. The model showed that 3 mg/kg/week SC administration of muM17 in mice
      is the minimum dose that can produce PD effects similar to those produced
      following 1 mg/kg/week SC of efalizumab in humans.

PMID- 16637055
TI  - Conservation laryngeal surgery versus total laryngectomy for radiation failure in
      laryngeal cancer.
AB  - BACKGROUND: Total laryngectomy is the standard of care for surgical salvage of
      radiation failure in laryngeal cancer. However, the role of conservation
      laryngeal surgery in this setting remains unclear. The objective was to compare
      the efficacy of conservation versus total laryngectomy for salvage of radiation
      failure in patients who initially presented with T1 or T2 squamous cancer of the
      larynx. METHODS: A 21-year retrospective analysis of patients who received
      surgery at a single comprehensive cancer center after definitive radiation
      therapy is reported. At recurrence, the patients were reevaluated and then
      underwent a total laryngectomy or, if possible, a conservation laryngeal
      procedure. The charts of 105 patients who failed radiation treatment for primary
      laryngeal cancer and who subsequently underwent surgical salvage were reviewed
      for this study. Eighty-nine were male (84.8%). The mean age was 60.3 years. The
      median follow-up time after surgery was 69.4 months. Most patients with
      recurrence after radiotherapy required total laryngectomy (69.5%; 73/105).
      Conservation laryngeal surgery was performed for 32 patients (31.5%). Concomitant
      neck dissections were performed on 45 patients (45.5%). RESULTS: In 14 patients,
      local or regional recurrence developed after salvage surgery: 9 patients after
      total laryngectomy (12.3%; 9/73), and 5 patients (15.6%; 5/32) after conservation
      laryngeal surgery. This difference was not statistically significant, nor was
      there a difference in disease-free interval for the two procedures (p = .634, by
      log-rank test). Distant metastasis developed in 13 patients. Most developed in
      the setting of local and/or regional recurrence, but distant metastasis occurred
      as the only site of failure in 6 of the patients who had undergone total
      laryngectomy but in 1 of the conservation surgery patients treated for a
      supraglottic laryngeal cancer. The overall mortality for patients who underwent
      total laryngectomy was also higher: 73.74% (54/73) versus 59.4% (19/32) for
      patients who underwent a conservation approach (p = .011 by log-rank test).
      CONCLUSIONS: Although conservation laryngeal surgery was possible in a few
      patients with local failure after radiotherapy, conservation laryngeal surgery is
      an oncologically sound alternative to total laryngectomy for these patients.

PMID- 16637056
TI  - Benign parathyroid cyst causing vocal fold paralysis: a case report and review of
      the literature.
AB  - BACKGROUND: Parathyroid cysts are uncommon, frequently asymptomatic lesions of
      the neck and superior mediastinum. Symptomatic parathyroid cysts are very rare,
      with roughly only 200 cases reported in the literature. Of these, only nine cases
      have been reported with recurrent laryngeal nerve (RLN) paralysis METHODS: We
      report a case of a 49-year-old man initially seen with a 6-month history of
      worsening hoarseness. Physical examination revealed a palpable 3-cm, firm,
      smooth, nontender mass of the right thyroid lobe. Fiberoscopic laryngoscopy
      showed right vocal cord immobility consistent with RLN paralysis. After CT and
      fine-needle aspiration of the mass, the patient underwent a right thyroid
      lobectomy. During surgery, the recurrent laryngeal nerve was found to be
      stretched and adherent to a right inferior lobe mass. RESULTS: Histologic
      analysis of the surgical specimen revealed a benign parathyroid adenomatous cyst.
      Postoperatively, the patient's voice improved markedly. This case represents an
      extremely rare return of function of the RLN after cyst removal. CONCLUSION:
      Parathyroid cysts should be included in the differential diagnosis for vocal fold
      paralysis.

PMID- 16637057
TI  - Increased expression of nuclear factor E2 p45-related factor 2 (NRF2) in head and
      neck squamous cell carcinomas.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) continues to cause
      significant morbidity and mortality. Overexpression of specific phase II gene
      products may represent an important biomarker. One regulator of phase II gene
      expression is the transcription factor nuclear factor E2 p45-related factor 2
      (Nrf2). Nrf2 expression was evaluated in HNSCC, to determine whether it might
      serve as a biomarker for early detection of disease. METHODS: A tissue microarray
      was constructed of 141 HNSCC biopsy cores from 47 HNSCCs. In addition,
      histologically normal squamous mucosa was obtained from 7 patients. Protein
      expression was evaluated by immunohistochemistry. RESULTS: Nrf2 expression was
      increased in 91.5% of tumors. Expression of thioredoxin, a Nrf2-reguated gene
      product, was elevated in 75% of tumors. Keap1, which regulates the rate of Nrf2
      ubiquitination and degradation, was relatively overexpressed in HNSCC compared
      with normal mucosa. CONCLUSIONS: Nrf2 expression may be a possible HNSCC
      candidate biomarker.

PMID- 16637058
TI  - Possible role of duration of PKC-induced ERK activation in the effects of
      agonists and phorbol esters on DNA synthesis in Panc-1 cells.
AB  - Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) have been
      implicated in the effects of regulatory peptides on proliferation. We studied how
      ERK was activated by PKC following regulatory peptide or phorbol ester
      stimulation and we also investigated the effect of ERK activation on
      proliferation in Panc-1 cells. Panc-1 cells transfected with CCK1 receptors were
      treated with cholecystokinin (CCK), neurotensin (NT), or phorbol 12-myristate 13
      acetate (PMA). DNA synthesis was studied by measuring tritiated thymidine
      incorporation. PKC isoforms were selectively inhibited with Go6983 and 200 nM Ro
      32-0432, their translocation was detected by confocal microscopy and by
      subcellular fractionation followed by immunoblotting. ERK cascade activation was
      detected with phosphoERK immunoblotting and inhibited with 20 microM PD98059. PMA
      and CCK inhibited, NT stimulated DNA synthesis. These effects were inhibited by
      Ro-32-0432 but not by Go6983 suggesting the involvement of PKCepsilon in
      proliferation control. Confocal microscopy and subcellular fractionation
      demonstrated that PMA, CCK, and NT caused cytosol to membrane translocation of
      PKCepsilon and ERK activation that was inhibited by Ro-32-0432 but not by Go6983.
      ERK activation was prolonged following PMA and CCK, but transient after NT
      treatment. PMA, CCK, and NT all activated cyclinD1, while p21CIP1 expression was
      increased by only PMA and CCK, but not by NT; each of these effects is inhibited
      by PD98059. In conclusion, our results provide evidence for PKCepsilon-mediated
      differential ERK activation and growth regulation in Panc-1C cells.
      Identification of the mechanisms by which these key signaling pathways are
      modulated could provide a basis for the development of novel therapeutic
      interventions to treat pancreatic cancer.

PMID- 16637059
TI  - Modulating the affinity and the selectivity of engineered calmodulin EF-Hand
      peptides for lanthanides.
AB  - A set of engineered peptides (33 amino acids long) corresponding to the helix
      turn-helix (EF-Hand) motif of the metal-binding site I of the protein calmodulin
      from paramecium tetraurelia have been synthesized. A disulfide bridge has been
      introduced in the native sequence in order to stabilize a native-like
      conformation. The calcium-binding carboxylate residues in positions 20, 22, 24,
      and 31 were mutated into other amino acids and the influence of such mutations on
      the binding affinity of the peptides for calcium and lanthanides have been
      studied. It was shown that the binding affinity for terbium ions can be modulated
      with dissociation constants ranging from 40 nmolar to 40 mmolar. The study of the
      influence of the mutations on the terbium affinity showed that the residue in
      position 24 played a key role on the capability of the peptides to bind
      lanthanides and that the affinity could be enhanced by mutations on non
      coordinating positions. Such peptides with high affinity for lanthanides may
      facilitate the development of new highly sensitive biosensors to monitor the
      metal pollution in the environment.

PMID- 16637060
TI  - c-Fos is required for TGFbeta1 production and the associated paracrine migratory
      effects of human colon carcinoma cells.
AB  - In tumor cells that have lost responsiveness to the growth inhibitory effects of
      transforming growth factor beta (TGFbeta), increased TGFbeta production by the
      tumor cells often contributes to cancer progression, primarily through paracrine
      mechanisms. Here we investigated the major components of the activator protein-1
      (AP-1) complex in the TGFbeta1 promoter of human colon carcinoma cells (HCCCs).
      In contrast to untransformed epithelial cells (UECs), HCCCs displayed
      constitutive activation of AP-1 at the proximal AP-1 site in the human TGFbeta1
      promoter. Further, in contrast to the JunD and Fra-2 components present in the AP
      1 complex at this AP-1 site in UECs, c-Fos was the major detectable AP-1
      component in HCCCs. Thus, transcriptional factor switching had occurred in HCCCs
      relative to the UECs, with regard to the proximal AP-1 site of the human TGFbeta1
      promoter. Small interfering RNAs (siRNAs) against c-Fos significantly suppressed
      AP-1 activity at the relevant AP-1 site, and led to a decrease in TGFbeta1
      secretion by the HCCCs. Our results indicate for the first time that c-Fos
      binding at the TGFbeta1 promoter proximal AP-1 site in HCCCs is required for
      TGFbeta1 production by the tumor cells. Further, we demonstrated that blockade of
      TGFbeta1 secretion by c-Fos siRNA led to a suppression of the cellular migration
      and mitogenesis of NIH 3T3 fibroblasts in a paracrine fashion. Thus, c-Fos may
      have utility as a target for blocking tumor cell-secreted TGFbeta1, thereby
      suppressing the migratory behavior associated with the malignant phenotype of
      HCCCs.

PMID- 16637061
TI  - Prostate cancer chemoprevention by silibinin: bench to bedside.
AB  - Prostate cancer (PCA) is the most invasive malignancy and second leading cause of
      cancer deaths in American males. One approach to reduce PCA incidence, growth and
      metastasis is prevention and intervention targeted towards mitogenic and survival
      signaling and cell-cycle regulation. This approach is based on the rationale that
      overexpression of receptor tyrosine kinases (RTKs) and/or non-receptor tyrosine
      kinases leads to persistent autocrine stimulation of malignant cells for
      deregulated cell-cycle progression and uncontrolled growth. PCA progression has
      also been associated with transition from a paracrine to an autocrine
      relationship between receptors and growth ligands as this malignancy progresses
      to an advanced androgen-independent aggressive stage. Together, these studies
      suggest that targeting RTK-mediated signaling pathways along with cell-cycle
      regulators could be a practical and translational approach for PCA prevention and
      intervention. Here, we provide evidence that a naturally occurring nontoxic
      flavanoid, silibinin, targets the epidermal growth factor receptor (EGFR),
      insulin-like growth factor-1 receptor (IGF-1R) and NF-kappaB (nuclear factor
      kappa B) pathways in PCA. Furthermore, it modulates cell-cycle regulators,
      including cyclin-dependent kinases (CDKs), Cip/Kip and cyclins for its anticancer
      efficacy against PCA. Silibinin inhibits growth of PCA cells from human, mouse,
      and rat origins, and also suppresses human prostate tumor xenograft growth in
      nude mice. Silibinin also inhibits PCA growth in the transgenic adenocarcinoma of
      mouse prostate (TRAMP) mouse model. Now, silibinin has been entered into phase
      I/II clinical trials in human PCA patients where preliminary observations were
      suggestive of its further study in a larger base of the patient population.

PMID- 16637062
TI  - Cyclooxygenase-2 as a signaling molecule in radiation-induced bystander effect.
AB  - Radiation-induced bystander effect represents a paradigm shift in our
      understanding of the radiobiological effects of ionizing radiation in that
      extranuclear and extracellular effects may also contribute to the final
      biological consequences of exposure to low doses of radiation. Evidence suggests
      that targeted cytoplasmic irradiation results in mutation in the nucleus of the
      "hit" cells and that cells, which are not directly hit by an alpha particle,
      whether nuclear or cytoplasm, but are in the vicinity of one that does get hit,
      contribute to the genotoxic response of the cell population. Although radiation
      induced bystander effects have been well documented in a variety of biological
      systems, the mechanism is not known. Using the Columbia University charged
      particle beam in conjunction with a novel strip dish design, we showed recently
      that the cyclooxygenase-2 (COX-2) signaling cascade plays an essential role in
      the bystander process. Treatment of bystander cells with NS-398, which suppresses
      COX-2 activity, significantly reduced the bystander effect as well as the
      induction of the mitogen-activated protein kinase (MAPK) pathways. These results
      provided the first evidence that the COX-2-related pathway, which is essential in
      mediating cellular inflammatory responses, is the critical signaling link for the
      bystander phenomenon. A better understanding of the cellular and molecular
      mechanisms of the bystander phenomenon together with evidence of their occurrence
      in vivo will allow us to formulate a more accurate model in assessing the health
      effects of low doses of ionizing radiation.

PMID- 16637063
TI  - Pentagalloylglucose inhibits estrogen receptor alpha by lysosome-dependent
      depletion and modulates ErbB/PI3K/Akt pathway in human breast cancer MCF-7 cells.
AB  - Estrogens and estrogen receptors (ER) play important roles in estrogen-dependent
      and ER-positive breast cancer development. Inhibitors against estrogen
      biosynthesis or anti-estrogens have been used in breast cancer treatment for many
      years. The aim of this study was to determine whether pentagalloylglucose (5GG)
      has inhibitory effects on ER function. In the present study, we found that 5GG
      significantly reduced the growth of estrogen-responsive human breast cancer MCF-7
      cells, and suppressed the phosphorylation and protein level of estrogen receptor
      alpha (ERalpha). Interestingly, 5GG decreased ERalpha protein levels by promoting
      the degradation of ERalpha protein in the lysosome. The ERalpha can be activated
      through a ligand-dependent and/or a ligand-independent pathway. The activated Akt
      kinase was shown to directly phosphorylate ERalpha at its serine residues and
      cause ligand independent activation. Our results showed that 5GG might inhibit
      the phosphatidylinositol 3-kinase (PI3K)/Akt pathway either through directly
      inhibiting Akt kinase activity or through inhibiting phosphorylation of the
      upstream receptor tyrosine kinases. The depletion of ErbB family receptors,
      including epidermal growth factor receptor (EGFR), ErbB2, and ErbB3, was also
      observed. 5GG treatment also led to a dose-dependent decrease in the expression
      of the estrogen-activated cyclin D1 expression. These findings suggested that 5GG
      might be a useful chemopreventive or therapeutic agent for hormone-dependent
      breast cancer through suppressing the functions of ERalpha by lysosome-dependent
      depletion and modulating the ErbB/PI3K/Akt pathway.

PMID- 16637064
TI  - Inactivation of IkappaB contributes to transcriptional activation of
      spermidine/spermine N(1)-acetyltransferase.
AB  - Spermidine/spermine N(1)-acetyltransferase (SSAT) is a key enzyme in polyamine
      catabolism. We recently reported that the combination of N(1), N(11)
      diethylnorspermine (DENSPM) and 5-fluorouracil (5-FU) synergistically induces
      SSAT expression, depletes polyamine levels and causes apoptosis in colon cancer
      cells. To determine whether new RNA and protein synthesis is required for SSAT
      induction, we examined the effect of actinomycin D (ActD) and cycloheximide
      (CHX). ActD alone blocked the induction of SSAT expression; however, the
      combination of CHX and DENSPM markedly induced SSAT expression and caused
      mitochondrial damage, suggesting that an inhibitory labile protein is involved in
      SSAT transactivation. SSAT promoter analysis identified two putative Rel/Nuclear
      Factor kappaB (NFkappaB) binding sites. Thus, we hypothesized that IkappaB is the
      labile inhibitory protein and that its removal contributes to the activation of
      NFkappaB. CHX quickly eliminated the IkappaB protein in the cells and increased
      the levels of the two subunits of NFkappaB, p65 and p50, in the nucleus.
      Luciferase reporter gene assay showed that SSAT promoter constructs containing
      the two putative NFkappaB binding elements responded to CHX as well as TNFalpha,
      whereas the promoter without the two sites did not. Chromatin immunoprecipitation
      (ChIP) assay showed that NFkappaB was indeed bound to the SSAT promoter after CHX
      treatment. Further, dominant negative IkappaB attenuated the CHX and DENSPM
      induced SSAT expression and mitochondria damage. These results taken together
      suggest that the inhibition of IkappaB and activation of NFkappaB activate SSAT.

PMID- 16637065
TI  - The role of histone H3 phosphorylation (Ser10 and Ser28) in cell growth and cell
      transformation.
AB  - Histones are now regarded as integral and dynamic components of the machinery
      responsible for regulating gene transcription. Many types of cancer and other
      diseases are associated with translocations or mutations in chromatin-modifying
      enzymes and regulatory proteins. Much of the work in our laboratory has focused
      on identifying novel histone H3 kinases and the role of histone H3
      phosphorylation in cell proliferation and transformation. We are beginning to
      unravel the complexities of gene expression mediated by histone H3
      phosphorylation, which is induced by a whole host of diverse stimuli. Dissimilar
      cells respond differentially to distinct stimuli, and induction of gene
      expression is dependent on the type of stimuli, duration and strength of stimuli,
      state of the cell and of course, specific cell type. Thus, regulation of histone
      modifications and resultant gene expression is not just one- or two-dimensional
      but multidimensional, encompassing a huge array of factors. Significant findings
      such as the observation that histone H3 phosphorylation (Ser10) is critical for
      neoplastic cell transformation suggests that histone H3 may be a crucial target
      for cancer chemotherapy or genetic therapy in the future.

PMID- 16637066
TI  - Dysregulation of the endothelial cellular response to oxidative stress in cancer.
AB  - The traffic of molecules and cells across the vessel wall is gated by vascular
      endothelial cells. In accordance, these cells play an active role in regulating
      cardiovascular and systemic homeostasis and in modulating physiopathological
      processes such as inflammation. Dysfunction of the regulatory systems of the
      endothelium and its incapacity to efficiently deal with its physicochemical
      surrounding leads to disruption of endothelial integrity. For example,
      alterations of the selective endothelial cell permeability barrier are early
      events in the sequence of oxidative stress-mediated injury that may contribute to
      extravasation of circulating cancer cells. Several lines of evidence indicate
      that the regulation of the endothelial barrier is tightly regulated by activation
      of signaling pathways that converge on the regulation of actin cytoskeletal
      dynamics. In particular, the integrity of the endothelial layer in response to
      oxidative stress is tightly regulated by the balanced activation of the
      extracellular-signal regulated kinase (ERK) and the stress-activated protein
      kinase-2/p38 (SAPK2/p38) pathways. Activation of the SAPK2/p38 pathway is
      required to trigger actin polymerization, whereas activation of the ERK pathway
      by contributing to phosphorylate tropomyosin-1 triggers the formation of focal
      adhesions allowing the anchorage of actin filaments generated by SAPK2/p38 to
      bundle into stress fibers. Dysregulation of this equilibrium by inhibiting ERK
      leads to membrane blebbing, an early manifestation of oxidative toxicity that is
      associated with disruption of the endothelial layer integrity.

PMID- 16637067
TI  - Reduced expression of the Connexin26 gene and its aberrant DNA methylation in rat
      lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine.
AB  - Gap junctions are mediated by intercellular channels that connect adjacent cells
      and are composed of Connexin (Cx) proteins. A member of the Cx family, Cx26 is
      considered a potential tumor suppressor in several cancers. The expression of
      Cx26 gene and its methylation status in rat lung adenocarcinomas induced by N
      nitrosobis(2-hydroxypropyl)amine (BHP) were investigated. Six-wk-old male Wistar
      rats were given 2,000 ppm BHP in their drinking water for 12 wk and maintained
      without further treatment until they were sacrificed at 25 wk. A total of nine
      lung adenocarcinomas were obtained and total RNA was extracted to assess
      expression by real-time quantitative reverse transcription (RT)-polymerase chain
      reaction (PCR). Five out of nine adenocarcinomas showed reduced expression
      compared with normal lung tissue. We next performed a bisulfite sequence analysis
      to measure the methylation status of the 5' upstream region of the Cx26 gene in
      two normal lung tissues and five lung adenocarcinomas that showed reduced
      expression of Cx26. All five adenocarcinomas were highly methylated in the 5'
      upstream region, while the two normal lung tissues were unmethylated. This
      suggests that aberrant methylation of the Cx26 gene may be involved in the
      development of lung adenocarcinomas induced by BHP in rats.

PMID- 16637068
TI  - External urethral sphincter activity in a rat model of pudendal nerve injury.
AB  - AIMS: Pudendal nerve injury in the rat has been a useful animal model for
      studying stress urinary incontinence (SUI). However, the effect of pudendal nerve
      injury on activity of the external urethral sphincter (EUS) is relatively
      unexplored. The aims of this study were to examine voiding and the EUS
      electromyogram (EMG) in a durable SUI model in rats with bilateral or unilateral
      pudendal nerve transections. In addition, the effects of denervation on urethral
      anatomy were investigated. METHODS: A leak point pressure (LPP) test was first
      used to demonstrate that pudendal nerve transection induced SUI. Cystometry
      exhibited changes in voiding function and EUS-EMG measurements provided a
      quantitative evaluation of EUS activity during voiding. The morphological changes
      in sections through the mid-urethra were assessed with hematoxylin and eosin
      (H&E) staining. RESULTS: A significant decrease in average LPP was detected in
      rats 6 weeks after bilateral pudendal nerve transection (BPNT). Abnormal
      urodynamic measurements including a decrease in contraction amplitude and voided
      volume as well as an increase in contraction duration, and residual volume all
      indicated inefficient voiding. In addition EUS-EMG silent periods were reduced
      and the frequency of EUS-EMG bursting during voiding was increased. Atrophy of
      striated muscle in the EUS was also detected in rats with pudendal nerve
      transection(s). CONCLUSIONS: Our results indicate that pudendal nerve transection
      in rats decreases urethral outlet resistance and causes striated muscle atrophy
      in the EUS, EUS-EMG abnormalities and inefficient voiding. The results
      demonstrate that BPNT is a durable model for SUI.

PMID- 16637069
TI  - The impact of formal education and training on urodynamic practice in the United
      Kingdom: a survey.
AB  - AIM: A previous survey of personnel performing urodynamics had shown that half of
      the respondents thought that their training had been inadequate. In order to
      address this the outcome of a 4-day practical course for teaching urodynamics,
      which has been running since 1995 at the Bristol Urological Institute, was
      reviewed. We were not aware of any published studies that have assessed the
      impact of formal urodynamic training on clinical practice. With this in mind we
      set out to determine whether the education and training we had given had changed
      urodynamic practice in the UK. METHODS: Postal questionnaires were sent out to 84
      delegates who had attended the course over a 2-year period (2001-2003). Paired
      questionnaires were used to assess urodynamic practice before and after the
      course and also to establish whether their practice had changed as a direct
      result of attending the certificate course. RESULTS: The results suggested that
      79% of those responders had changed their practice since completing the course.
      Significant changes to practice were observed in checking calibration, confidence
      in setting-up equipment, interpretation of urodynamic traces and ability to check
      the accuracy of the results. CONCLUSIONS: The results of this survey suggest that
      attendance at a recognised urodynamic training course has had an impact on
      clinical practice in the UK. Training and education raises the level of
      confidence and ability to perform and interpret urodynamic investigations, which
      has wide implications for the accuracy, reliability and consistency of urodynamic
      investigations performed by those without formal training.

PMID- 16637070
TI  - Comparison of pelvic floor muscle training, electromyography biofeedback, and
      neuromuscular electrical stimulation for bladder dysfunction in people with
      multiple sclerosis: a randomized pilot study.
AB  - AIM: Bladder dysfunction affects up to 90% of the multiple sclerosis (MS)
      population. Interventions such as Pelvic Floor Training and Advice (PFTA),
      Electromyography (EMG) Biofeedback, and Neuromuscular Electrical Stimulation
      (NMES) have received limited research attention within this population. This
      study aimed to determine the effectiveness of a combined programme of PFTA, EMG
      Biofeedback, and NMES for bladder dysfunction in MS. METHODS: Females (n = 30)
      who fulfilled strict inclusion/exclusion criteria were recruited. Outcome
      measures (weeks 0, 9, 16, and 24) included: 3-day Voiding Diary; 24 hr Pad-Test;
      Uroflowmetry; Pelvic Floor Muscle Assessment; Incontinence Impact Questionnaire
      (IIQ); Urogenital Distress Inventory (UDI); King's Health Questionnaire (KHQ),
      and the Multiple Sclerosis Quality of Life-54 Instrument (MSQoL-54). Following
      baseline (week 0) assessment, participants were randomly allocated, under double
      blind conditions, to one of the three groups: Group 1 (PFTA); Group 2 (PFTA and
      EMG Biofeedback); and Group 3 (PFTA, EMG Biofeedback, and NMES). Treatment was
      for 9 weeks. RESULTS: Baseline severity (measured by number of leaks and pad
      weight) showed some variation between groups, although not statistically
      significant (P > 0.05); with the caveat that this baseline imbalance makes
      interpretation difficult, a picture emerges that at week 9, Group 3 demonstrated
      superior benefit as measured by the number of leaks and pad test than Group 2,
      with Group 1 showing less improvement when compared to week 0; this was
      statistically significant between Groups 1 and 3 for number of leaks (P = 0.014)
      and pad tests (P = 0.001), and Groups 1 and 2 for pad tests (P = 0.001). A
      similar pattern was evident for all other outcome measures. CONCLUSION: Results
      suggest that these treatments, used in combination, may reduce urinary symptoms
      in MS. Further research will establish the effectiveness of these interventions.

PMID- 16637071
TI  - PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen
      independent prostate cancer proliferation.
AB  - BACKGROUND: Promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional
      repressor and negative regulator of the cell cycle, has been characterized as a
      prostatic androgen-responsive gene. DU145 cells show androgen-independent growth
      and lack PLZF gene expression. METHODS: We analyzed PLZF-regulating genes by DNA
      microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.
      RESULTS: DNA microarray revealed that Pbx1 is a prominent suppressed gene in PLZF
      overexpressing DU145 cells. Androgen receptor (AR)-expressing DU145 cells
      recovered androgen-dependent PLZF expression and subsequent repression of Pbx1
      expression. Immunoprecipitation of Pbx1 in DU145 cells revealed a Pbx1-HoxC8
      heterocomplex. siRNAs for Pbx1 and HoxC8 knocked downexpression of each, and this
      suppressed androgen-independent cell growth. Double knockdown of both Pbx1 and
      HoxC8 suppressed cell growth much more significantly. CONCLUSIONS: Androgen
      independent cell line DU145 cells lack PLZF gene expression, resulting in the
      upregulation of Pbx1 and HoxC8 expression. The Pbx1-HoxC8 heterocomplex may lead
      to androgen-independent growth in prostate cancer.

PMID- 16637072
TI  - Germline ATBF1 mutations and prostate cancer risk.
AB  - BACKGROUND: ATBF1 has been recently identified as a candidate prostate tumor
      suppressor gene. In addition to more unique mutations, two somatic mutations
      (shortening of a polypyrimidine tract [Poly(T)n] and a deletion beginning at
      codon 3381 (3381del)) were each observed in multiple prostate cancer samples and
      both appear to have an impact on ATBF1 gene function and expression. METHODS: We
      assayed two recurrent sequence variants in germline DNA from prostate cancer
      cases and controls, and examined whether carriers of these variants are at
      increased risk for prostate cancer. RESULTS: We found Poly(T)n variants in both
      normal and matched tumor DNA samples from multiple patients, indicating a
      germline origin in each case. Genotyping germline DNA samples indicated that
      3381del was significantly associated with prostate cancer risk among sporadic
      cases (P = 0.03), but not among men with hereditary disease. CONCLUSIONS: Our
      study indicates that the germline 3381del allele may influence prostate cancer
      susceptibility.

PMID- 16637073
TI  - Conditional expression of PTEN alters the androgen responsiveness of prostate
      cancer cells.
AB  - BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is
      lost as a function of prostate tumor androgen dependence. While the
      transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in
      androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is
      unclear. METHODS: We developed a system where PTEN can be conditionally re
      expressed at physiologic levels into a PTEN null metastatic human CaP cell line,
      C4-2, and androgen responsiveness examined. RESULTS: PTEN induction reduces cell
      growth and blocks the growth effect of synthetic androgen R1881. The anti
      androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is
      independent of Akt phosphorylation. Combined PTEN induction and Casodex, result
      in a further decrease in prostate specific antigen promoter activity compared to
      PTEN but not Casodex alone. CONCLUSIONS: PTEN induction confers androgen
      independent CaP cells enhanced responsiveness to the anti-proliferative effects
      of anti-androgens and this action may involve non-AR mediated effects.

PMID- 16637074
TI  - Protocadherin-PC promotes androgen-independent prostate cancer cell growth.
AB  - BACKGROUND: Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis
      resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we
      assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate
      tissues. METHODS: LNCaP cells transfected with PCDH-PC were tested for their
      ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC
      mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ
      hybridization. RESULTS: PCDH-PC expression induced Wnt signaling in CaP cells and
      permitted androgen-independent growth of hormone-sensitive CaP cells. Expression
      of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells
      in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells
      expressed significantly higher levels of PCDH-PC-related mRNA. CONCLUSIONS: Our
      findings suggest a novel mechanism for the progression of CaP involving
      expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes
      malignant behavior and hormone-resistance of CaP cells.

PMID- 16637075
TI  - The effects of short-term oral phytoestrogen supplementation on the hypothalamic
      pituitary-testicular axis in prostate cancer patients.
AB  - BACKGROUND: Here we evaluate the effects of oral phytoestrogen supplementation on
      hypothalamic-pituitary-testicular (HPT) axis in CaP patients. METHODS: We
      recruited 40 men about to undergo radical prostatectomy for CaP to receive either
      240 mg of clover phytoestrogens or placebo daily for 2 weeks. Serum hormone
      levels were measured before and after treatment. In addition, recombinant cell
      bioassay was used to measure serum androgen bioactivity (ABA). RESULTS:
      Phytoestrogen treatment increased serum LH from mean of 3.4-5.2 IU, P = 0.03.
      Concomitantly, non-significant trend towards decline in serum T, cfT and ABA
      values was noted. However, mean serum LH/T ratio was upregulated from 0.20 to
      0.48 IU/nM, P = 0.004, suggesting compensated hypogonadism. During the course of
      treatment, serum concentration of equol correlated strongly with the concomitant
      decrease in ABA (r = -0.586, P = 0.022). CONCLUSIONS: Phytoestrogen treatment
      interferes with HPT axis in CaP patients by inducing testicular resistance to LH
      and compensated hypogonadism.

PMID- 16637076
TI  - Monomethylated selenium inhibits growth of LNCaP human prostate cancer xenograft
      accompanied by a decrease in the expression of androgen receptor and prostate
      specific antigen (PSA).
AB  - OBJECTIVES: Epidemiological studies and prevention trials suggest selenium is a
      promising preventive agent for prostate cancer. Selenium-containing compounds
      inhibited the growth of prostate cancer cell lines including androgen sensitive
      LNCaP and androgen insensitive DU145 and PC3 cells in vitro. Previous study
      revealed a novel mechanism of selenium action in which selenium (methylseleninic
      acid (MSA)) markedly reduced androgen receptor (AR) signaling in prostate cancer
      cells, suggesting that selenium might act as an antiandrogen, which could serve
      as a therapeutic agent for prostate cancer. In this study, we tested whether
      selenium (methylselenocysteine (MSC)) affects tumor growth of human prostate
      cancer cells by targeting AR signaling in vivo. METHODS: Prostate tumor
      xenografts were established in nude mice by co-inoculating LNCaP cells with
      Matrigel. The mice-bearing tumors were treated with or without MSC (100
      microg/mouse/day) via intraperitoneal injection for 2 weeks. The effect of MSC on
      tumor growth, AR, and prostate-specific antigen (PSA) expression was examined.
      RESULTS: Methylselenocysteine (MSC) significantly inhibited LNCaP tumor growth (P
      < 0.05). AR expression in tumor tissues and serum PSA levels were considerably
      decreased in MSC-treated mice compared to the vehicle controls. CONCLUSIONS:
      Pharmacological dose of MSC inhibits the growth of LNCaP human prostate cancer in
      vivo accompanied by a decrease in the expression of AR and PSA. These findings
      suggest that selenium (MSC) can serve as a therapeutic agent aimed at disruption
      of AR signaling for prostate cancer.

PMID- 16637077
TI  - Biochemical progression rates in the screen arm compared to the control arm of
      the Rotterdam Section of the European Randomized Study of Screening for Prostate
      Cancer (ERSPC).
AB  - BACKGROUND: The European Randomized study of Screening for Prostate Cancer
      (ERSPC) investigates the feasibility of population-based screening. This report
      compares the preliminary outcome of cancers detected in the screen and the
      control arm of its Rotterdam section, by means of biochemical progression rates.
      METHODS: In the screen arm of this study (21,210 men), screening was applied
      according to well-established protocols, and a 4-year screen interval was chosen.
      Widely accepted biochemical progression-criteria were used to evaluate the
      diagnosed cancers over time. RESULTS: Although more cancers were detected in the
      screen than in the control arm (1,339 vs. 298, P < 0.001), their clinico
      pathological features were more favorable. Furthermore, screened men had higher 5
      year survival rates for biochemical progression after surgery (84.4% vs. 58.9% in
      controls), radiotherapy (71.0% vs. 58.0%), and endocrine therapy (40.5% vs.
      16.3%). CONCLUSIONS: The higher biochemical progression-free survival can at
      least in part be explained by lead and length-time. How screening will effect the
      mortality remains unclear.

PMID- 16637080
TI  - Single and double pH-driven Cu2+ translocation with molecular rearrangement in
      alkyne-functionalized polyamino polyamido ligands.
AB  - A new series of ligands, containing one (L1H(2)-L4H(2)) or two (L5H(4)-L6H(4))
      1,4,8,11-tetraaza-5,7-dione units and functionalized with a propargyl group on
      the C atom between the C=O moieties, has been synthesized. Protonation constants
      for the ligands and formation constants of their Cu(2+) complexes have been
      determined in water, and the coordination geometry of the complexes existing at
      various pH values has been investigated by coupled pH-metric and
      spectrophotometric titrations. Ligands capable of simple uptake of Cu(2+) with
      the formation of neutral, square-planar complexes containing the -2-charged
      diamino-diimido donor sets and ligands containing further coordinating groups
      (quinoline or pyridine) capable of single and double cation translocation have
      been investigated. The role of the substituents on the amino groups and the
      structural role played by the propargyl group have been examined as regards
      Cu(2+) complexation and translocation. In the double-translocating ligand L6H(4),
      when the two Cu(2+) ions move inside the diamino-diamido donor set, the slim
      propargyl group allows an unprecedented folding of the whole ligand with apical
      coordination of one pyridine to form a five-coordinate, square-pyramidal Cu(2+)
      ion. The crystal and molecular structures of this unusual [L6Cu(2)] complex have
      been determined by X-ray diffraction. Finally, oxidation of Cu(2+) to Cu(3+) has
      been studied by cyclic voltammetry in water, which revealed that the redox
      reaction occurs only when the copper cation is within the diamino-diimido
      compartment. Moreover, both functionalization of the primary amines with bulky
      substituents and apical coordination of Cu(2+) make access to the 3+ oxidation
      state more difficult and disrupt the reversibility of the electrochemical
      process.

PMID- 16637081
TI  - Synthesis of sulfated galactocerebrosides from an orthogonal beta-D
      galactosylceramide scaffold for the study of CD1-antigen interactions.
AB  - CD1a protein binds sulfatide (3-O-sulfo-beta-D-galactosylceramide) to form an
      antigen complex that interacts with T cell receptors and activates T cells. To
      assess the role of the position of the sulfate in T cell activation, the
      synthesis of three beta-D-galactosylceramides, variously bearing a sulfate at
      position 2, 4, or 6 of galactose, has been planned and carried out. The compounds
      were synthesized by an orthogonal sulfation strategy from a common beta-D
      galactosylceramide scaffold, which was in turn obtained through an efficient
      glycosylation reaction between a fully orthogonally protected galactosyl imidate
      and 3-O-benzoylazidosphingosine. Immunological evaluation of the three sulfated
      compounds in CD1a-mediated T cell activation, in comparison with natural
      sulfatide, provided evidence of the influence of the sulfate position in the
      recognition event between the antigen, the CD1 protein and the T cell receptor.

PMID- 16637082
TI  - Direct asymmetric intermolecular aldol reactions catalyzed by amino acids and
      small peptides.
AB  - In nature there are at least nineteen different acyclic amino acids that act as
      the building blocks of polypeptides and proteins with different functions. Here
      we report that alpha-amino acids, beta-amino acids, and chiral amines containing
      primary amine functions catalyze direct asymmetric intermolecular aldol reactions
      with high enantioselectivities. Moreover, the amino acids can be combined into
      highly modular natural and unusual small peptides that also catalyze direct
      asymmetric intermolecular aldol reactions with high stereoselectivities, to
      furnish the corresponding aldol products with up to >99 % ee. Simple amino acids
      and small peptides can thus catalyze asymmetric aldol reactions with
      stereoselectivities matching those of natural enzymes that have evolved over
      billions of years. A small amount of water accelerates the asymmetric aldol
      reactions catalyzed by amino acids and small peptides, and also increases their
      stereoselectivities. Notably, small peptides and amino acid tetrazoles were able
      to catalyze direct asymmetric aldol reactions with high enantioselectivities in
      water, while the parent amino acids, in stark contrast, furnished nearly racemic
      products. These results suggest that the prebiotic oligomerization of amino acids
      to peptides may plausibly have been a link in the evolution of the homochirality
      of sugars. The mechanism and stereochemistry of the reactions are also discussed.

PMID- 16637083
TI  - The Bingel monoadducts of La@C82: synthesis, characterization, and
      electrochemistry.
AB  - The reaction of La@C82 with diethyl bromomalonate in the presence of base (the
      Bingel reaction) generated five monoadducts which have been fully characterized.
      It was found that four of them (mono-A, -B, -C, and -D) are ESR-inactive,
      suggesting singly bonded regioisomers. In contrast, the fifth product (mono-E) is
      ESR-active, indicating that it possesses a cyclic moiety between the appended
      malonate group and the fullerene cage, analogous to conventional Bingel adducts.
      The differences in the molecular structures of mono-A, -B, -C, and -E result in
      varying thermal stabilities and electrochemical behavior. In particular, the
      singly bonded monoadducts undergo the retro-Bingel reaction either under thermal
      treatment or during electron transfer on the cyclic voltammetric timescale.
      However, mono-E shows remarkable thermal stability and perfect reversibility
      under the same experimental conditions.

PMID- 16637084
TI  - A facile method for oxidation of primary alcohols to carboxylic acids and its
      application in glycosaminoglycan syntheses.
AB  - A convenient two-step, one-pot procedure was developed for the conversion of
      primary alcohols to carboxylic acids. The alcohol was first treated with NaOCl
      and TEMPO under phase-transfer conditions, followed by NaClO2 oxidation in one
      pot. This reaction is applicable to a wide range of alcohols and the mild
      reaction conditions are compatible with many sensitive functional groups,
      including electron-rich aromatic rings, acid-labile isopropylidene ketal and
      glycosidic linkages, and oxidation-prone thioacetal, p-methoxybenzyl, and allyl
      moieties. Several glycosaminoglycans such as heparin, chondroitin, and hyaluronic
      acid oligosaccharides have been synthesized in high yields by using this new
      oxidation protocol.

PMID- 16637085
TI  - NIR lanthanide luminescence by energy transfer from appended terpyridine
      boradiazaindacene dyes.
AB  - Mononuclear trivalent lanthanide complexes with formula [Ln(L)(NO(3))(3)] [in
      which L=4,4-difluoro-8-(2':2'';6'':2'''-terpyridin-4''-yl)-1,3,5,7-tetramethyl
      2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (Boditerpy)] are reported for Ln=Yb,
      Nd, Er, La and Gd. According to the crystal structure of the Yb complex, the
      lanthanide ion is bound to the terdentate terpyridine and the inner coordination
      sphere of the nine-coordinate lanthanide ion is completed by three bidentate
      nitrate anions. The coordination polyhedron can be described as a distorted
      tricapped antiprism. The terpyridine chelate is almost planar and tilted by
      nearly 60 degrees from the indacene subunit. FT-IR spectra confirm the bidentate
      binding mode of the nitrate anions for the other complexes. NMR and ES-MS spectra
      (through characteristic isotopic patterns) confirm the chemical formulation. The
      complexes have high molar absorption coefficients in the visible spectral region
      (65,000 M(-1) cm(-1) at 529 nm) and display sizeable NIR luminescence (900 to
      1600 nm, for Ln=Yb, Nd and Er), upon irradiation through the electronic state of
      the indacene moiety at 514 nm. Crystal-field splitting was analysed at low
      temperature. The quantum yield of the Yb solution (10(-4) M) in dichloromethane
      amounts to 0.31 %, corresponding to a sensitisation efficacy of the ligand of ca.
      63 %.

PMID- 16637086
TI  - Deconvoluting the memory effect in Pd-catalyzed allylic alkylation: Effect of
      leaving group and added chloride.
AB  - An analysis of product distributions in the Tsuji-Trost reaction indicates that
      several instances of reported "memory effects" can be attributed to slow
      interconversion of the initially formed syn- and anti-[Pd(eta3-allyl)] complexes.
      Addition of chloride triggers a true memory effect, in which the allylic terminus
      originally bearing the leaving group has a higher reactivity. The latter effect,
      termed regioretention, can be rationalized by ionization from a palladium complex
      bearing a chloride ion, forming an unsymmetrically substituted [Pd(eta3-allyl)]
      complex. DFT calculations verify that the position trans to the phosphine ligand
      is more reactive both in the initial ionization and in the subsequent
      nucleophilic attack.

PMID- 16637087
TI  - CO fixation to stable acyclic and cyclic alkyl amino carbenes: stable amino
      ketenes with a small HOMO-LUMO gap.

PMID- 16637088
TI  - Rational design of a well-defined soluble calcium hydride complex.

PMID- 16637089
TI  - Femtosecond dynamics on 2-(2'-hydroxy-4'-diethylaminophenyl)benzothiazole:
      solvent polarity in the excited-state proton transfer.
AB  - Detailed insights into the excited-state enol(N*)-keto(T*) intramolecular proton
      transfer (ESIPT) reaction in 2-(2'-hydroxy-4'-diethylaminophenyl)benzothiazole
      (HABT) have been investigated via steady-state and femtosecond fluorescence
      upconversion approaches. In cyclohexane, in contrast to the ultrafast rate of
      ESIPT for the parent 2-(2'-hydroxyphenyl)benzothiazole (>2.9+/-0.3 x 10(13) s(
      1)), HABT undergoes a relatively slow rate (approximately 5.4+/-0.5 x 10(11) s(
      1)) of ESIPT. In polar aprotic solvents competitive rate of proton transfer and
      rate of solvent relaxation were resolved in the early dynamics. After reaching
      the solvation equilibrium in the normal excited state (N(eq)*), ESIPT takes place
      with an appreciable barrier. The results also show N(eq)*(enol)<-->T(eq)*(keto)
      equilibrium, which shifts toward N(eq)* as the solvent polarity increases.
      Temperature-dependent relaxation dynamics further resolved a solvent-induced
      barrier of 2.12 kcal mol(-1) for the forward reaction in CH(2)Cl(2). The observed
      spectroscopy and dynamics are rationalized by a significant difference in dipole
      moment between N(eq)* and T(eq)*, while the dipolar vector for the enol form in
      the ground state (N) is in between that of N(eq)* and T(eq)*. Upon N-->N* Franck
      Condon excitation, ESIPT is energetically favorable, and its rate is competitive
      with the solvation relaxation process. Upon reaching equilibrium configurations
      N(eq)* and T(eq)*, forward and/or backward ESIPT takes place with an appreciable
      solvent polarity induced barrier due to differences in polarization equilibrium
      between N(eq)* and T(eq)*.

PMID- 16637090
TI  - Passion for precision.
AB  - Optical frequency combs from mode-locked femtosecond lasers have revolutionized
      the art of counting the frequency of light. They can link optical and microwave
      frequencies in a single step, and they provide the long missing clockwork for
      optical atomic clocks. By extending the limits of time and frequency metrology,
      they enable new tests of fundamental physics laws. Precise comparisons of optical
      resonance frequencies of atomic hydrogen and other atoms with the microwave
      frequency of a cesium atomic clock are establishing sensitive limits for possible
      slow variations of fundamental constants. Optical high harmonic generation is
      extending frequency comb techniques into the extreme ultraviolet, opening a new
      spectral territory to precision laser spectroscopy. Frequency comb techniques are
      also providing a key to attosecond science by offering control of the electric
      field of ultrafast laser pulses. In our laboratories at Stanford and Garching,
      the development of new instruments and techniques for precision laser
      spectroscopy has long been motivated by the goal of ever higher resolution and
      measurement accuracy in optical spectroscopy of the simple hydrogen atom which
      permits unique confrontations between experiment and fundamental theory. This
      lecture recounts these adventures and the evolution of laser frequency comb
      techniques from my personal perspective.

PMID- 16637091
TI  - Catalytic epoxidation and 1,2-dihydroxylation of olefins with bispidine
      iron(II)/H2O2 systems.

PMID- 16637092
TI  - The association of water in ionic liquids: a reliable measure of polarity.

PMID- 16637093
TI  - Chemoselective benzylic C-H activations for the preparation of condensed N
      heterocycles.

PMID- 16637094
TI  - Catalytic enantioselective crossed aldehyde-ketone benzoin cyclization.

PMID- 16637095
TI  - Alcohols in isonitrile-based multicomponent reaction: Passerini reaction of
      alcohols in the presence of o-iodoxybenzoic acid.

PMID- 16637096
TI  - Threat of "suboptimal" blood pressure control rises with age.

PMID- 16637097
TI  - Novel heart failure drug may offer options for you.

PMID- 16637098
TI  - What's it mean when researchers say a medical study is controlled? Aren't all
      studies controlled in some way? And while you're at it, what's randomized mean?

PMID- 16637099
TI  - Cracking the tax code.

PMID- 16637101
TI  - Emerging into the light.

PMID- 16637100
TI  - Written in the blood.

PMID- 16637102
TI  - In May, I received  stents in two arteries, and two more stents in an artery
      treated more than ten years ago. The doctor told me to return in six months for a
      catheterization to make sure the stents were working. Do I really need that
      catheterization, or would a heart CT scan be a viable option?

PMID- 16637103
TI  - Adjusting to the 80-hour work week.

PMID- 16637104
TI  - Neural prosthetics: science fact.

PMID- 16637105
TI  - Diabetic nephropathy.

PMID- 16637106
TI  - Emergency physicians' voice in the ACLS protocol: guideline's Eclectic Committee
      should serve as model.

PMID- 16637107
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Updated U.S. Public Health Service guidelines for the management of
      occupational exposures of HIV and recommendations for postexposure prophylaxis.

PMID- 16637108
TI  - Evidence-based emergency medicine/systematic review abstract. Rhythm versus rate
      control for atrial fibrillation and flutter.

PMID- 16637109
TI  - Evidence-based emergency medicine/systematic review abstract. Does this patient
      have a torn meniscus or ligament of the knee?

PMID- 16637110
TI  - Investigation in tea on fate of fenazaquin residue and its transfer in brew.
AB  - Fenazaquin is a non-systemic acaricide/insecticide used widely in controlling
      mites and other related pests in fruits, vegetables and tea. The objective of
      this research was to investigate the disappearance trend in tea of fenazaquin
      residue level and its transfer in brew. Fenazaquin was applied on a tea crop at
      two rates, 125 and 250 g AI/ha in wet and dry seasons under field conditions.
      Samples (green shoots, made tea and its brew) were analyzed for fenazaquin and
      quantification was by high performance liquid chromatography using a UV detector.
      The residue dissipated faster in the wet season than in the dry season. Seven
      days after the treatment (normal round of plucking) the residues observed in the
      green shoots at the two rates were 2.17, 3.07 mg/kg and 2.04, 2.84 mg/kg in the
      wet and dry seasons, respectively. However, the degradation rale in both seasons
      followed first-order kinetics. Half-lives in green shoots were in range 1.43-1.70
      and 2.10-2.21 days and in made tea 1.59-1.73 and 1.87-1.94 days for wet and dry
      seasons, respectively. During processing of green shoots to made tea considerable
      loss (42-70%) of residue was observed. The transfer of residue from made tea brew
      was in the range 3-22%. In brew residue were below 0.02 mg/l after 5 days of
      application at both the rates in either of the seasons. The estimated intake with
      brew (normal consumption of 10 cup/day/adult) thus would be below the acceptable
      daily intake for fenazaquin (0.005 mg/kg-body weight). To avoid health hazards
      due to the toxic effect of residues in brew, a waiting period for plucking the
      tea shoots after fenazaquin application of more than 5 days for both the seasons
      at recommended rate (125 g AI/ha) may be suggested and considered quite safe.

PMID- 16637111
TI  - The voltage dependence of recovery from use-dependent block by QX-222 separates
      mechanisms for drug egress in the cardiac sodium channel.
AB  - In neuronal sodium channels of squid giant axons, recovery from QX-222 block is
      slowed by hyperpolarization. However, in ventricular cells, hyperpolarization
      speeds recovery. Previously, we showed that isoform-specific residues in the
      external side of the cardiac sodium channel isoform (D1P-loop C373 and D4S6
      T1752) influence use-dependent block (UDB) by lidocaine. To determine whether
      these isoformspecific residues contribute to the contrasting voltage-dependent
      recovery observed in ventricular myocytes, we measured recovery rates from UDB by
      QX-222 at holding potentials of 120, 140, 160 and 180 mV for wild-type cardiac
      channel (WT), the mutants C373Y (CY) and T1752V (TV), and C373Y/T1752V (CY/TV).
      Unlike neuronal channels, cardiac sodium channels recovered from QX block faster
      at hyperpolarized potentials. All mutations slowed QX-222 recovery, with the
      greatest rate reduction observed for the double mutant, indicating that the
      isoform-specific residues define external drug paths. The recovery rates varied
      linearly with voltage over the range tested, and we used the slopes of rate
      versus voltage plots to quantify voltage dependence. The TV mutation caused
      reduction in recovery rates without changing the slope, indicating that the
      mutation closed a voltage-independent egress path. The CY mutation, however,
      flattened the slope and reduced the voltage dependence of recovery. In addition,
      the reduction in rate caused by CY/TV is less than the sum of those for CY and
      TV, suggesting that the impacts of these two residues are interrelated.
      Therefore, we propose that the isoform-specific residues C373 and T1752 change
      recovery from UDB by distinct mechanisms but determine a common drug egress path.

PMID- 16637112
TI  - Reconstructing virginity in Guatemala.

PMID- 16637113
TI  - Health reforms further anger Germany's striking doctors.

PMID- 16637114
TI  - Opinion remains divided over Chernobyl's true toll.

PMID- 16637115
TI  - Corruption targeted in Romania's health reforms.

PMID- 16637116
TI  - New strategies may halt the atopic march.

PMID- 16637117
TI  - Health tips. Buying glasses.

PMID- 16637118
TI  - No needle insulin.

PMID- 16637119
TI  - Managing nausea. When treatments make you ill.

PMID- 16637121
TI  - Are blood pressure machines in drugstores accurate?

PMID- 16637120
TI  - Keeping the beat. Heart assist devices.

PMID- 16637122
TI  - Getting a 'GRIPP' on the research-policy interface in New South Wales.

PMID- 16637123
TI  - The Bangkok Charter for Health Promotion in a Globalized World: what is it all
      about?

PMID- 16637124
TI  - Builders, boomers, busters, bridgers: vive la (generational) difference!

PMID- 16637125
TI  - Segmentation on a shoestring: health audience segmentation in limited-budget and
      local social marketing interventions.

PMID- 16637126
TI  - Symposium and workshop on healthy lifestyle programs for weight management.

PMID- 16637127
TI  - [Abstracts of the 6th National Congress of Urology, Tunis, Tunisia, 3-4 February
      2006].

PMID- 16637128
TI  - Abstracts of the 2nd Latin American Congress of Autoimmunity.

PMID- 16637129
TI  - Bioethics of teaching about reproductive technology and prenatal diagnosis
      choices in Japan.
AB  - The results of teaching trials among students in Japan are reported, examining
      their attitudes towards prenatal diagnosis and ART over a course of lectures. The
      students tended to be more negative than the general public over the use of
      prenatal diagnosis. The results of attitude changes, and example comments to
      explain the categorization process are given. The students had a diversity of
      comments and could reason about the examples of technology used, but were
      characterized by a higher percentage of uncertainty than in the general public
      even after lectures on bioethics.

PMID- 16637130
TI  - [Abstracts of the 2nd Croatian Gerontological Congress with international
      participation, March 9-12, 2006, Opatija, Croatia].

PMID- 16637131
TI  - Common ethical issues in regenerative medicine.
AB  - One of the common ethical issues in regenerative medicine is progress in
      'componentation' (= being treated as parts) of the human body, and the
      enhancement of the view of such "human body parts." 'Componentation' of the human
      body represents a preliminary step toward commodification of the human body. The
      process of commodification of the human body follows the steps of
      'materialization' (= being treated as a material object) [first step] --
      'componentation' [second step] -- 'resourcialization' (= being treated as
      resources) [third step] -- commodification [fourth step]. Transplantation
      medicine and artificial organ developments have dramatically exposed the
      potential of organs and tissues as parts, and regenerative medicine has a role in
      advancing 'componentation' of the human body and further enhancing the view of
      human body parts. The 'componentation' of the human body, regardless of the
      degree of regenerative medicine's contribution to it, is considered as a
      challenge to the traditional view of human bodies and the abstract value of
      "Human Dignity" in the same way or alongside the 'resourcialization' and
      commodification. However, in the future, a new perspective of human bodies that
      means "a perspective whereby human bodies, organs, tissues, and even the bodies
      themselves are perceived as disposable tools like disposable cameras, syringes,
      or contact lens" and therefore a new ethical view, suitable for a new reality,
      may emerge.

PMID- 16637132
TI  - The model and moral justification for organ procurement in Japan.
AB  - Organ replacement therapy is a part of medical practice in today's world and many
      countries have adopted the required guidelines and regulations. Establishing the
      basis on which organs can be removed, is still one of the most controversial
      issues of health policy making in the debate. The critical disparity between
      supply and demand in organ replacement therapy, even with the existence of social
      acceptance and organ transplantation law, turns attention towards the importance
      of an appropriate model of organ procurement. This model should be able to expand
      the donor pool and increase the organ retrieval rate by converting potential
      donors to actual ones. In Japan the organ transplantation law which was enacted
      in 1997 allows organ procurement from brain death as well as non-heart beating
      cadavers according to restricted conditions. One such condition includes the
      necessity of both the donor's and the family's written consent. Under current
      organ procurement policy, organs from only 29 brain death cases have been so far
      procured. In this paper after examining the current organ procurement system in
      Japan and the moral justifications behind different organ procurement models we
      conclude that the Japanese system does not clearly fall into one of the popular
      organ procurement models.

PMID- 16637133
TI  - The organ transplant law of Japan--the past, the present, and the future.
AB  - The Organ Transplant Law of Japan, which regulates organ transplants using brain
      dead persons' organs, has a set of extremely severe intention-requirements. It
      has stagnated, rather than promoted, the organ transplant in Japan for the last 8
      years. We believe that the Law should be reformed by making an about-face from
      the current "opt-in" to the "opt-out" principle.

PMID- 16637134
TI  - Applications for human rights relief and the recommendations of the Japan
      Federations of Bar Associations.
AB  - Between the enactment of Japan's "Organ Transplantation Law" (OTL) in 1997 and
      the end of October 2003, there were 27 (30 now) legal declarations of brain
      death, and organs were donated from 26 (29) of those. During this period, four
      applications for human rights relief were made against organ donation facilities
      by Takayoshi Okamoto and others. One of these remains under investigation, but
      the Japanese Federation of Bar Associations (JFBA) has offered recommendations
      relating to the other three. The purpose of this report lies in examining these
      applications and recommendations.

PMID- 16637135
TI  - Quality assessment of autografting by probability evaluation: model estimation by
      clinical end-points in newly diagnosed multiple myeloma patients.
AB  - BACKGROUND: Pre-transplant clinical evaluation of autografting is an important
      step in predicting post-transplant support, complications and safety. Today,
      unfavorable outcomes such as early death or graft failure are rare, making them
      unsuitable for quality assessment of supportive autografting. However, end-points
      constructed from frequently occurring clinical events may estimate clinically
      relevant prognostic models. METHODS: The present retrospective analysis was based
      on two consecutive clinical trials in the Nordic area including up to 640 newly
      diagnosed multiple myeloma patients. RESULTS: In the model, the efficacy (time on
      antibiotics and use of transfusions) was influenced by pre-transplant variables,
      including sex, nationality, serum creatinine, hemoglobin, disease stage at
      diagnosis, response following induction therapy, length of priming and average
      graft CD34+ cell number per day of harvest. The toxicity end-point (time to blood
      cell recovery) was influenced by nationality, marrow plasma cell percentage,
      serum creatinine, M-component isotype, response to induction therapy, length of
      priming and graft CD34+ cell number. The safety (early disease recurrence or
      death) was influenced by serum creatinine, hemoglobin, treatment response and
      CD34+ cell number. DISCUSSION: In conclusion, the model illustrates that
      intervention strategies in quality assessment of autografting may benefit from
      probability estimates of graded clinical end-points.

PMID- 16637136
TI  - Reconsidering the dead donor rule.
AB  - If we abide by the dead donor rule, we have to comply with the rule that an organ
      donor must be declared to be irreversibly and unequivocally dead and not merely
      dying before the commencement of organ extraction. In this paper, I will show the
      following: that living donor transplantations violate the dead donor rule; that
      we cannot say that not only all the brain dead patients (HBDs) but also all the
      cardiac arrest patients (NHBDs) have been irreversibly and univocally dead at the
      time of organ extraction; and that we do not know how to tell living potential
      donors from dead potential donors.

PMID- 16637137
TI  - "Death with dignity" in the Japanese context.
AB  - In Japan, "death with dignity" is a widely known term that is distinguished from
      "euthanasia." It is generally defined as "the act of letting a terminally ill or
      a patient in a persistent vegetative state die by withdrawing life-sustaining
      treatment on request in the form of a living will." Most Japanese people consider
      death with dignity a desirable way of terminating one's life and it is therefore
      acceptable as a "natural death" or "humane death." Originally, death with dignity
      was regarded as a passive intervention, but since the 1990s, its connotations
      have changed in western countries; people claim that voluntary active euthanasia
      and physician-assisted suicide should be legalized as death with dignity or the
      "right to die." In this paper, I examine the points and problems of this new type
      of death with dignity and propose an alternative version of death with dignity
      especially for the Japanese context, i.e. the end-of-life care process in support
      of terminal living with dignity.

PMID- 16637138
TI  - End-of-life care and advance directives in Japan.
AB  - This paper examines the ethical issues concerning Advance Directives (ADs) and
      surveys the current Japanese situation. ADs were devised as a means of expressing
      the refusal to live in deep unconsciousness. This is validated as the patient's
      self-determined right to end his/her life in America. This trend affects Japan as
      well, where the move toward legislation for ADs is seen at present. Many Japanese
      people think that ADs should be respected because wishes in advance comprise the
      patient's autonomous decision concerning life-sustaining treatment and death with
      dignity. However, there are some ethical issues with ADs. The situation
      surrounding ADs is very uncertain. We cannot prove that a wish in deep
      unconsciousness and wish in advance are the same. In addition, medical prognoses
      are not always right. Such uncertainty gives rise to the ethical issue of
      consistency of advance autonomous decisions. It appears that many people are not
      aware of the ethical issues, and that there is little public discussion on ADs.
      Therefore, this paper explores why the Japanese have not argued the ethical
      issues concerning ADs. Finally, I speculate on the major problems and asks of
      ADs, and provide materials for the future examination of ADs.

PMID- 16637139
TI  - Informed consent in Malaysia: an overview.
AB  - The right of a person to control his body is a concept that has long been
      recognized in Malaysia under the law of torts. The purpose of requiring informed
      consent is to preserve that right in medical decision-making. Informed Consent is
      a relatively new concept in medical litigation cases. However in the late 1990's,
      it has become one of the important claims under negligence made against the
      doctor for failure to disclose relevant information to patients in respect of the
      treatment proposed. Whether Malaysia has begun to recognize patient's right to
      decision-making is yet to be seen. Furthermore the social-cultural relationship
      between doctors and patients had to be considered. In this respect, the
      researcher had conducted interviews with doctors and patients to gauge their
      reaction towards a shared process of decision-making, which is the central issue
      in the doctrine of informed consent. Findings suggest that in society where
      primary health care is the main thrust to achieve health for all, the possibility
      of recognition of the rights of patients to receive information before making
      decisions about treatment appears remote. The findings also underscore the
      importance of incorporating aspects of informed consent as part of providing
      quality service to patients.

PMID- 16637140
TI  - [Advice no. 22 of 19 May 2003 concerning the choice of sex for non-medical
      reasons].

PMID- 16637141
TI  - [Ethical aspects of banks of umbilical cord blood, advice no. 19 of 16 March
      2004].

PMID- 16637142
TI  - Assessing and managing contaminated sediments: part I, developing an effective
      investigation and risk evaluation strategy.
AB  - This is the first of a two-part review of the current state-of-the-science
      pertaining to the assessment and management of contaminated sediments. The goal
      of this review is to introduce some of the major technical and policy issues
      stemming from the assessment and management of contaminated sediments, highlight
      a number of aspects of contaminated sediment assessment and management found to
      be successful, and, when appropriate, address the barriers that still exist for
      improving contaminated sediment management. In this paper, Part I, the many key
      elements of an effective investigation and risk evaluation strategy are reviewed,
      beginning with the development of a conceptual site model (CSM) and including a
      discussion of some of the key factors influencing the design of sediment
      investigations and ecological risk assessment of sediment-bound chemicals on
      aquatic biota. In Part II of this paper (Apitz et al. 2005), various approaches
      are reviewed for evaluating sediment risk and monitoring sediment remedy
      effectiveness. While many of the technical and policy issues described in this
      review are relevant to dredged material management, the focus of this paper is on
      sediment assessment for environmental management.

PMID- 16637143
TI  - Relating results of chronic toxicity responses to population-level effects:
      modeling effects on wild Chinook salmon populations.
AB  - Standard toxicity tests assess the physiological responses of individual
      organisms to exposure to toxic substances under controlled conditions. Time and
      space restrictions often prohibit the assessment of population-level responses to
      a toxic substance. Compounds affecting various toxicity endpoints, such as
      growth, fecundity, behavior, or immune function, alter different demographic
      traits and produce different impacts on the population. Chronic effects of immune
      suppression, reproductive impairment, and growth reduction were examined using
      life history models for Chinook salmon (Oncorhynchus tshawytscha). Modeled immune
      suppression acted through reductions in age-specific survival, with first- and
      second-year survival producing the greatest changes in the population growth rate
      (lamda). A 10% reduction in various reproductive parameters all produced a
      similar lamda, but different sensitivity and stable age distributions. Growth
      reduction models incorporated effects to both survival and reproduction and
      produced additive effects. Overall, model output indicated that for Chinook
      salmon, alteration of first-year survival has the greatest relative impact on
      lamda. Results support the importance of linking toxicity endpoints to the
      demographic traits that they influence and help generate toxicity tests that are
      more relevant for the species. Life history modeling provides a useful tool to
      develop testable hypotheses regarding specific and comparative population-level
      impacts.

PMID- 16637144
TI  - Ecological risk assessment of polycyclic aromatic hydrocarbons in sediments:
      identifying sources and ecological hazard.
AB  - Polycyclic aromatic hyftovst ond (PAH) are nearly ubiqutous contaminants of
      freshwater and marine sediments. Sediment PAHs are derived from combustion of
      organic matter, fossil fuels, and biosynthesis by microbes. Pyrogenic PAHs,
      particularly those associated with combustion particles (soot), have a low
      accessibility and bioavailability in sediments. Polycyclic aromatic hydrocarbons
      associated with petroleum, creosote, or coal tar in sediments may have a moderate
      accessibility/bioavailability, particularly if the PAHs are part of a nonaqueous
      phase liquid (NAPL) phase that is in contact with sediment pore water. We present
      a method for estimating the hazard of complex PAH assemblage in sediments to
      benthic organisms. Concentrations of all PAHs in sediment pore water are
      estimated by an equilibrium partitioning model relative to concentrations in bulk
      sediment. Predicted log Koc values can be used for predicting sediment/water
      partitioning of petrogenic PAH, but empirically derived log Kd values are needed
      to predict partitioning of pyrogenic PAH. A hazard quotient (HQ) for each PAH is
      calculated as the ratio of the estimated concentration in pore water to the
      chronic toxicity of the PAH determined by a log Kow/toxicity model. Hazard
      quotients for all PAH in a sample are summed to produce a hazard index (HI),
      which is a measure of the worst-case estimated hazard of the sediment PAH to
      benthic organisms. The results of this study show that the integration of HI
      results with PAH source data provides insights into the causes of sediment
      toxicity that are useful in an ecological risk assessment.

PMID- 16637145
TI  - Effects of dissolved organic carbon on copper toxicity: implications for
      saltwater copper criteria.
AB  - During the past three decades, significant advances have been made in
      understanding how environmental factors modify the bioavailability and the
      toxicity of metals such as copper in aquatic environments. Several of these
      advances have led to the development of guidelines to indirectly account for
      modifying factors, adjustment of criteria on a site-specific basis, and direct
      changes to the U.S. Environmental Protection Agency (U.S. EPA) freshwater quality
      criteria. To date, most of this effort has focused on freshwater systems,
      although similar modifying factors exist in marine environments as well. This
      paper focuses on one such modifying factor, dissolved organic carbon (DOC), and
      describes a method to aid in risk assessments or to refine the saltwater copper
      criteria on a site-specific basis. The relationship between DOC and toxicity of
      copper to the most sensitive saltwater genus in the U.S. EPA criteria database,
      Mytilus, is extensively analyzed. Dissolved copper 50% effective concentrations
      (EC50s) are highly correlated (r2 = 0.71, n=54, p < 0.001) across a wide range of
      sample DOC concentrations (0.3-10 mg carbon [C]/L) and are explained by the
      equation EC50 = 11.53DOC(0.54). Two equations based on DOC are proposed for
      consideration as a means for deriving site-specific final chronic criteria (FCC)
      and final acute criteria (FAC) for copper in marine and estuarine environments
      (Copper FCC(DOC) = 3.71DOC(0.54) and Copper FAC(DOC) = 5.843DOC(0.54).

PMID- 16637146
TI  - A PBTK/TD modeling-based approach can assess arsenic bioaccumulation in farmed
      tilapia (Oreochromis mossambicus) and human health risks.
AB  - A biologically based risk-assessment model of arsenic (As) exposure evaluated
      farmed tilapia (Orechromis mossambicus) and human health during tilapia
      consumption in an area of southwestern Taiwan where blackfoot disease (BFD)
      occurs. The risk assessment addressed exposures to city residents who lived in
      Taipei, Taichung, and Kaohsiung, as well as subsistence fishers living in the BFD
      area who consumed tilapia. The models implemented included a physiologically
      based toxicokinetic and toxicodynamic (PBTK/TD) model to account for As exposure
      and dose-response profiles in tilapia and a human health exposure/risk model that
      accounts for target lifetime risk (TR) and hazard quotient (HQ) for humans
      consuming farmed tilapia. Results demonstrated that 90th percentiles of TR ranged
      from 1.53 x 10(-8) to 1.62 x 10(-6) for city residents with farmed tilapia
      consumption rates of 0.41 to 1.37 g/d. The 90th percentiles ranged from 2.07 x
      10(-6) to 7.89 x 10(-5) for subsistence fishers in the BFD area with farmed
      tilapia consumption rates of 16.80 to 59.15 g/d. All predicted 90th percentiles
      of HQ were less than 1 for city residents and subsistence fishers in the BFD
      area, indicating small contributions from farmed tilapia consumption. Critical
      variables included whole-fish body weight, water As content, and As level in
      tilapia muscle. Although bioaccumulation of As seems unlikely to result in
      toxicity to farmed tilapia and humans consuming tilapia, the theoretical human
      health risks in the BFD area are alarming, using a probabilistic risk-assessment
      model based on conservative assumptions.

PMID- 16637147
TI  - Consideration of soil properties in assessment of human health risk from exposure
      to arsenic-enriched soils.
AB  - Encroachment of residential development on agricultural lands in the United
      States where arsenical pesticides were extensively used prior to the 1990s has
      increased the potential for human exposure to arsenic (As), a group A carcinogen.
      Soil ingestion by children is a critical issue in assessing health risks from
      exposure to As-enriched soils. In the absence of a universal "soil model" on As
      bioavailability, many baseline risk assessment studies use the assumption that
      all (100%) As present in soil is bioavailable. However, As exists in many
      geochemical forms as dictated by soil chemical properties. Because As
      bioavailability is a function of soil speciation, using total soil arsenic values
      potentially overestimates human health risk, thereby increasing site cleanup
      expenses. A laboratory incubation study was conducted to estimate in vitro As
      bioavailability as a function of soil properties in four chemically variant soil
      types contaminated with sodium arsenite pesticide. Results demonstrate that As
      speciation in certain soils translates to significant lowering of As
      bioavailability and hence potential cancer risk.

PMID- 16637148
TI  - Life cycle assessment in management, product and process design, and policy
      decision making: a conference report.
AB  - On 24 September 2003, life cycle assessment (LCA) practitioners and decision
      makers gathered at the InLCA/LCM Conference in Seattle, Washington, USA (see
      http://www.lcacenter.org/InLCA-LCM03/index.html) to discuss the role of LCA in
      management, product design, process development, and regulatory/policy
      development decisions and to compare life cycle-based methods and tools with
      traditional product evaluation methods and tools. This article is a summary of
      that meeting and was prepared by the organizers as an overview of the many
      different technical, regulatory policy, and decision-making policy perspectives
      presented to an international gathering of participants representing academia and
      the industrial and regulatory communities.

PMID- 16637149
TI  - A critical assessment of the ecological risk assessment process: a review of
      misapplied concepts.
AB  - A frank assessment of present-day ecological risk assessments (ERA) for managed
      contaminated sites reveals that fundamental concepts regarding the receptors that
      are considered and the chemical exposures they experience are commonly
      misapplied. As a consequence, environmental managers are not being supplied with
      the information needed for proper decision making. The stepwise review of
      ecological risk issues provided here suggests that the ERA process needs I to be
      severely revamped. Further, what is likely hindering the development of a refined
      ecological assessment process that is better suited to environmental problem
      solving and land management is the unwillingness of stakeholders to agree that
      much of the current ERA practice and convention is flawed.

PMID- 16637150
TI  - Ecological risk assessment issues identified during the U.S. Environmental
      Protection Agency's examination of risk assessment practices.
AB  - Recently, the U.S. Environmental Protection Agency examined its current risk
      assessment principles and practices. As part of the examination, aspects of
      ecological risk-assessment practices were reviewed. Several issues related to
      ecological risk assessment were identified, including the use of organism-level
      versus population-level attributes to characterize risk, the possible
      opportunities associated with the increased use of probabilistic approaches for
      ecological risk assessment, and the notion of conservatism in estimating risks.
      The agency examination provides an understanding of current practices and is
      intended to begin a dialogue in which the risk assessment community can engage in
      addressing the identified issues to improve and enhance ecological risk
      assessment.

PMID- 16637151
TI  - The future direction of ecological risk assessment in the United States:
      reflecting on the U.S. Environmental Protection Agency's "Examination of risk
      assessment practices and principles".
AB  - As part of an agency evaluation of the development of risk assessment tools, the
      U.S. Environmental Protection Agency (U.S. EPA) issued a staff paper in March
      2004 describing the current state of practices and policies regarding risk
      assessment from the agency's perspective. The staff paper provided a rationale
      for the agency's positions regarding technical topics frequently the subject of
      comments or complaints. Considerations relevant to ecological risk assessment
      were included, primarily in a single chapter focused on this topic. This
      commentary highlights four technical issues important to the advancement of
      ecological risk assessment practice and discusses how some of the points raised
      by the U.S. EPA in the staff paper have significance to ecological risk
      assessors. Discussion regarding incorporating population- and community-level
      analysis into risk assessments and the apparent reluctance of the U.S. EPA to
      adopt advances in this area is provided. Also, continuing inconsistencies in the
      body weight scaling of toxicity values between human health and ecological risk
      assessment practices are discussed. Ideas for refining the calculation of
      exposure point concentrations for ecological receptors and the progression
      between screening steps and comprehensive risk assessment are also discussed.

PMID- 16637152
TI  - Protecting Native Americans through the risk assessment process: A commentary on
      "an examination of U.S. EPA risk assessment principles and practices".

PMID- 16637153
TI  - The U.S. Environmental Protection Agency's examination of its risk assessment
      principles and practices: a brief perspective from the regulated community.
AB  - In March 2004, the U.S. Environmental Protection Agency (U.S. EPA) published a
      review of its risk assessment principles and practices. In examining this review,
      we find a broad, but not particularly deep, review by the authors and areas where
      the U.S. EPA should strive to further improve the risk assessment process.
      Recommended areas of improvement include the use of less conservative default
      assumptions, calculating risk based on populations instead of individuals, and
      fostering research on multiple stressors and their impacts on estimating risks to
      ecological receptors.

PMID- 16637154
TI  - Life without methyl bromide: the Italian experience in replacing the fumigant.
AB  - Methyl bromide (MB) has been the most widely used chemical for the fumigation of
      soil, commodities, buildings and furniture for over seventy years. Since January
      1st 2005, it has been phased-out in industrialized countries, where only critical
      uses are allowed, because of international regulatory measures designed to reduce
      substances that potentially deplete the stratospheric ozone layer. Italy ranked
      second in the world, after USA, in MB consumption, due to the importance of
      horticultural crop production. In order to replace the use of MB, research in
      Italy was aimed at: a) reducing the use of MB and its emission (short-term goal);
      b) developing alternative pest control methods, based on available technologies
      (mid-term goal); c) developing new MB alternatives (mid- and long-term goal).
      Italian growers switched to other fumigants, applied at reduced dosages, lowering
      their environmental impact and risk of worker exposure. Moreover, the adoption of
      non-chemical alternatives slowly but steadily increased as a result of the many
      activities (demonstration trials, seminars, etc.) carried out in the country. The
      gradual shift to MB alternatives over a 10 year period, as well as the use of
      half rates of MB under virtually impermeable plastic films (VIFs), has generally
      prevented the feared loss of competitiveness of Italian horticulture. Extension
      in cooperation with the fumigation companies was able to provide growers with a
      range of methods for soil disinfestation. The experience gained in Italy and how
      it can help developing countries to define strategies and training programmes
      needed to comply with the Montreal Protocol is discussed.

PMID- 16637155
TI  - Soil suppressiveness to Rhizoctonia solani and microbial diversity.
AB  - Rhizoctonia solani anastomosis group 2-2IIIB causes damping-off, black root rot
      and crown rot in sugar beet (Beta vulgaris). Based on experiences of growers and
      field experiments, soils can become suppressive to R. solani. The fungus may be
      present in the soil, but the plant does not show symptoms. Understanding the
      mechanisms causing soil suppressiveness to R. solani is essential for the
      development of environmentally friendly control strategies of rhizoctonia root
      rot in sugar beet. A bioassay that discriminates soils in their level of disease
      suppressiveness was developed. Results of bioassays were in accordance with field
      observations. Preliminary results indicate an active role of microbial
      communities. Our research is focused on the disentanglement of biological
      mechanisms causing soil suppressiveness to R. solani in sugar beet. Therefore, we
      are handling a multidisciplinary approach through experimental fields, bioassays,
      several in vitro techniques and molecular techniques (PCR-DGGE).

PMID- 16637156
TI  - Induction of resistance to the pathogenic agent Botrytis cinerea in the
      cultivation of the tomato by means of the application of the protein
      "Harpin"(Messenger).
AB  - Harpin(Ea), an active component in Messenger, was originally isolated from the
      bacterial plant pathogen Erwinia amylovora based on its ability to elicit a
      hypersensitive response (HR). This bacterial pathogen causes "fire blight", a
      disease in apples and other members of the Rosaceae. Harpin(Ea) also induces
      resistance in a variety of plants against a wide array of pathogens. The
      objective of this investigation was to determine indications of resistance
      induction to Botrytis cinerea in the plants treated with the formulated
      Harpin(Ea) protein. This pathogenic agent is responsible for important economic
      losses in the cultivation of both greenhouse and field grown tomatoes. Plants
      with and without Messenger applications were inoculated with Botrytis cinerea in
      the same way. In addition, some plants with and without Messenger applications
      were not inoculated. Inoculated plants were symptomatologically checked for local
      and systemic symptoms. Evaluations of the number of tomatoes produced and their
      growth were also carried out. The results obtained demonstrate that there were
      active defence systems in the plant, producing a reduction in the damage caused
      by the pathogenic agent Botrytis cinerea. A greater growth also took place in the
      fruit obtained. These results show that the formulated Harpin(Ea) protein could
      reduce the use of chemical agents and be a new tool to serve as the basis for an
      Integrated Pest Management system.

PMID- 16637157
TI  - Effects of the foliar-applied protein "Harpin(Ea)" (messenger) on tomatoes
      infected with Phytophthora infestans.
AB  - The active ingredient in Messenger, is Harpin(Ea), a naturally occurring protein
      derived from Erwinia amylovora, a causal agent of fire blight. When Messenger is
      applied to a plant, the protein Harpin(Ea) binds foliar receptors to it. The
      receptors recognize the presence of Harpin(Ea), sending a signal that a pathogen
      is present, actually "tricking" the plant into thinking that it is under attack.
      This binding process triggers a cascade of responses affecting a global change of
      gene expressions, stimulating several distinct biochemical pathways within the
      plant responsible for growth and disease and insect resistance. The objective of
      this work is to characterize the development of an induced resistance against
      Phytophthora infestans. No effective treatment is currently available against
      this pathogenic agent, which causes the loss of complete harvests of different
      crops. Tomato plants with and without Messenger applications were inoculated with
      Phytophthora infestans in the same way. In addition, some plants with and without
      Messenger applications were not inoculated. Inoculated plants were
      symptomatologically checked for local and systemic symptoms. Evaluations of the
      number of tomatoes produced, with or without damage, and their growth, were also
      carried out. Based on the data obtained from the assays, significant changes were
      observed in the parameters measured due to Messenger treatment. The severe damage
      of this disease was reduced in the plants which received Messenger applications.
      These results open up new pathways in the control of diseases like Phytophthora
      infestans, in which effective means to combat them still do not exist, or these
      means are harmful to the environment.

PMID- 16637158
TI  - Development of a biological control method against postharvest diseases of citrus
      fruits.
AB  - Candida oleophila strain O was previously selected for its high and reliable
      antagonistic activity against Botrytis cinerea and Penicillium expansum, two
      important wound pathogens on post-harvest apples. The application of these
      antagonistic strains on wound pathogens of Citrus was more recently undertaken.
      The efficacy of yeast (applied at several concentrations from 10(5) to 10(8)
      CFU/ml) was assessed against P. digitatum and P. italicum inoculated after one
      hours (at a concentration of 10(5), 106 and 10(7) spores/ml) on 'Clementine' and
      'Valencia late' varieties. The protective levels were positively correlated with
      high concentration of antagonist and low concentration of pathogen. The
      antagonistic activity of this strain was also dependent on the incubation time
      before pathogen inoculation. The protective level increased with time between
      application of the antagonist and inoculation of fungal spores. Finally, the
      efficacy of biomass of C. oleophila strain O (produced at an industrial scale),
      and two different formulations of that biomass was assessed in comparison with
      fungicidal treatment (Thiabendazole) under semi-practical conditions against P.
      digitatum. This efficacy of strain O (whatever its formulation) was statistically
      comparable to that for TBZ at commercial dose, indicating that both formulations
      could be used as an alternative for conventional fungicide in postharvest
      treatments.

PMID- 16637159
TI  - Microsatellite markers for resistance to spot blotch in spring wheat.

PMID- 16637160
TI  - Botrytis infection warnings in strawberry: reduced enhanced chemical control.
AB  - The fungal pathogen Botrytis cinerea is the causal agent of grey mould, the most
      important fungal fruit rot disease in strawberry in Europe. Currently disease
      control for grey mould is based on preventive spraying every five to seven days
      during flowering and harvest. Replacing preventive spraying with applications
      based on infection warnings can optimize performance and reduce the amount of
      sprays needed. Success of this approach will depend on the accuracy of the model
      used to predict disease outbreak. For this reason three infection models (BOTEM,
      BoWaS, DSS-Italy) were evaluated during the growth seasons of 2003 and 2004. The
      experiments included June bearing, retarded June bearing and ever bearing
      strawberries. In all experiments the use of infection models leaded to a reduced
      number of fungicide applications. However the efficacy of the different models
      towards the control of B. cinerea also decreased compared to the efficacy
      obtained with a standard 7 day schedule. Best results were obtained with BOTEM,
      developed by HRI (Horticultural Research International, East-Malling, UK): 17-60%
      reduction in fungicide use and an efficacy between 66-93 depending on the growth
      season, culture practice and the fungicides used. Compared with routine
      preventive spraying, the Botrytis fruit rot percentage is slightly higher. A
      higher efficacy with Botrytis infection warnings can only be obtained if
      infection warnings change from curative to preventive. A retroactive evaluation
      of a preventive warning system was included. Making use of the 48h weather
      forecasts supplied by the Royal Meteorological Institute of Belgium (KMI) based
      on ALADIN for the region of Haspengouw, it was possible to replace 30 up to 100%
      of the curative application by preventive spraying depending on the experiment
      and the threshold set for the preventive model.

PMID- 16637161
TI  - Sensitivity of Venturia inaequalisto strobilurin fungicides in Italy.

PMID- 16637162
TI  - A new post-harvest fungicide to control fruit rot on apple and pear.
AB  - PHILABUSTER is a new post-harvest fungicide developed by Janssen Pharmaceutica
      N.V.. It provides an advanced mould control by post-harvest treatments of citrus
      and pome fruit. The product is formulated as a stable suspension concentrate
      intended for dilution in water before use. PHILABUSTER 400 SC contains 200 g/L
      imazalil and 200 g/L pyrimethanil. Both active ingredients have a different
      single site mode of action. Imazalil inhibits ergosterol biosynthesis (DMI),
      whereas pyrimethanil interferes with fungal enzyme secretion and methionine
      biosynthesis. Due to the combination of these low risk fungicides a good anti
      resistance management can be obtained. In case of existing reduced sensitivity of
      a population to DMI or MBC fungicides, no cross-resistance with pyrimethanil was
      observed. PHILABUSTER showed good activity by post-harvest treatment against key
      pathogens on apple and pear Penicillium expansum (blue mold), Botrytis cinerea
      (gray mold) and Gloeosporium spp. (lenticel rot) in small and large scale
      experiments with artificial or natural infections. By dip treatment of large
      volumes of fruit (up to 50 tons) the depletion of both active ingredients in the
      treatment water was low, both when plastic or wooden bins were used. Lower dose
      rates resulted in an inferior and inconsistent residue level of both active
      ingredients on fruit. Possible advantages of post-harvest treatments versus field
      treatments for the control of storage diseases are discussed.

PMID- 16637163
TI  - Individual and combined effects of dosages of azoxystrobin and epoxiconazole in
      wheat.
AB  - The effects of single fungicide applications on Mycosphaerella graminicola
      (septoria leaf blotch) control and winter wheat yield were evaluated in field
      trials conducted in central Belgium between 2000 and 2004. Individual
      applications of 25, 50, 75 and 100% of the manufacturer's recommended dose rates
      of azoxystrobin and epoxiconazole, and all the combinations of these treatments,
      were made at GS 39 in 2001 to 2004 and at GS 59 in 2000. Disease assessments were
      made at growth stage 75, some 7-8 weeks after the last applications. Between 2000
      and 2003, no significant difference was observed for disease control between the
      products when applied alone. With regard to the dose responses, the differences
      between the recommended dose rates and the 50% reduced dosages were not
      important. In 2004, azoxystrobin was less effective than epoxiconazole. This was
      probably the result of strobilurin-resistant isolates of M. graminicola reaching
      an occurrence of 32% before fungicide application. The combination of different
      dosages of azoxystrobin and epoxiconazole revealed that there was very little
      synergy between these products when applied in a single application. The
      combinations of these products were better than individual applications only when
      high dosages of both compounds were used.

PMID- 16637164
TI  - Pseudomonads associated with midrib rot and soft rot of butterhead lettuce and
      endive.
AB  - During the past ten years, bacterial soft rot and midrib rot of glasshouse-grown
      butterhead lettuce (Lactuca sativa L. var. capitata) and field-grown endive
      (Cichorium endivia L.) has become increasingly common in the region of Flanders,
      Belgium. Severe losses and reduced market quality caused by bacterial rot
      represent an important economical threat for the production sector. Symptoms of
      midrib rot are a brownish rot along the midrib of one or more inner leaves, often
      accompanied by soft rot of the leaf blade. Twenty-five symptomatic lettuce and
      endive samples were collected from commercial growers at different locations in
      Flanders. Isolations of dominant bacterial colony types on dilution plates from
      macerated diseased tissue extracts yielded 282 isolates. All isolates were
      characterized by colony morphology and fluorescence on pseudomonas agar F medium,
      oxidase reaction, and soft rot ability on detached chicory leaves. Whole-cell
      fatty acid methyl esters profile analyses identified the majority of isolates
      (85%) as belonging to the Gammaproteobacteria, which included members of the
      family Enterobacteriaceae (14%) and of the genera Pseudomonas (73%),
      Stenotrophomonas (9%), and Acinetobacter (3%). Predominant bacteria were a
      diverse group of fluorescent Pseudomonas species. They were further
      differentiated based on the non-host hypersensitive reaction on tobacco and the
      ability to rot potato slices into 4 phenotypic groups: HR-/P- (57 isolates), HR
      /P+ (54 isolates), HR+/P (16 isolates) and HR+/P+ (35 isolates). Artificial
      inoculation of suspensions of HR-, pectolytic fluorescent pseudomonads in the
      leaf midrib of lettuce plants produced various symptoms of soft rot, but they did
      not readily cause symptoms upon spray inoculation. Fluorescent pseudomonads with
      phenotype HR+ were consistently isolated from typical dark midrib rot symptoms,
      and selected isolates reproduced the typical midrib rot symptoms when spray
      inoculated onto healthy lettuce plants.

PMID- 16637165
TI  - Watermark disease in willow and its relation to Brenneria salicis dominance in
      the wood.

PMID- 16637166
TI  - Detection and epidemiological characteristics of peach latent mosaic viroid in
      Tunisia.
AB  - A rapid and sensitive assay was developed for the detection and identification of
      Peach latent mosaic viroid (PLMVd) by reverse transcription-polymerase chain
      reaction (RT-PCR) in infected tissues from Tunisian orchards. The test was
      initially performed by using total RNA preparations from selected isolates and
      then applied on total RNA preparations from leaf or bark tissues of fruit trees
      collected in 2003 in 20 orchards in the North of Tunisia and the Sahel. PLMVd
      occurred in peach and pear trees. The identity of the detected viroid was
      confirmed by comparison of its sequence with other isolates previously
      characterized. The test was then simplified by direct use of diluted crude plant
      extracts. The results obtained from crude sap extracts of leaves or bark tissues
      are identical to those obtained from total RNA preparations. Epidemiological
      characteristics of PLMVd on peach trees have been investigated. A survey of peach
      trees was carried out in 32 orchards in May 2004. The obtained results showed
      that (1) PLMVd is highly and equally present in several regions of the north of
      Tunisia rather than the central, the Sahel and the southern regions, (2)
      infection percentage increases with the age of the tree and (3) the studied
      cultivars are classified into three groups of sensitivity.

PMID- 16637167
TI  - Fusarium spp. and Fusarium mycotoxins in maize: a problem for Flanders?
AB  - Fusarium species cause not only root, stem and ear rot with severe reductions in
      crop yield, they produce also toxic secondary metabolites (mycotoxins) such as
      deoxynivalenol (DON) and zearalenone (ZEA). During several growing seasons the
      presence of Fusarium spp was followed up. DON and ZEA were determined and related
      to infection levels. The distribution of DON and ZEA in the different plant parts
      was studied as well as the influence of the ensiling process on the mycotoxin
      content. More or less important varietal differences in susceptibility for
      Fusarium spp. could be detected. DON and ZEA were clearly present in most of the
      analysed samples. No clear relationship could be detected between visual disease
      symptoms and mycotoxin content. The accumulation of DON and ZEA was different for
      the analysed aerial plant parts. The ensiling process gave no reduction of the
      mycotoxin content.

PMID- 16637168
TI  - Identification of anastomosis group of Rhizoctonia solani, the causal agent of
      seed rot and damping-off of bean in Iran.
AB  - Bean is one of the major crops in Iran. Seed rot and damping-off caused by
      Rhizoctonia solani is the most important disease of bean. In this research,
      infected roots and seedlings of beans were collected from different fields of
      Tehran Province. The samples were sterilized with 10% sodium hypochloride (5%
      stock) and incubated on PDA surface in petri-dishes. The purified fungi kept on
      filter paper and identified, pathogenicity test of R. solani was carried out on 2
      cultivars of bean (red bean cv. Naz and white bean cv. Dehghan) and it
      determined. For identification of the anastomosis groups, the discs of cultured
      media with 5 mm. diameter of standard AG placed on one side of microscopic slides
      covered with water agar (2%) of 1 mm. thick and the isolates of the fungus on
      another side of slide about 2 cm away from each other. Experiment carried out in
      4 replications. The cultures were incubated in 25 +/- 1 degrees C incubator for
      24 hours, then the mycelial contact stained with lactophenol, cotton blue and
      hyphal anastomosis looked for under the light microscope with 10 x 40 and 10 x
      100 magnifications. As a result, anastomosis groups: AG4, AG4HGII, AG2-2-2B and
      AG6 determined, frequency of these groups were 64, 18, 2, 16%, respectively. The
      group AG6 and subgroups AG4HGII and AG2-2-2B are introduced as new anastomosis
      groups on bean in Iran.

PMID- 16637169
TI  - Selection of antagonists of postharvest apple parasites: Penicillium expansum and
      Botrytis cinerea.
AB  - The objectives of this study were to constitute a collection of pathogenic agents
      of economic importance which cause losses of apple fruits after harvest namely
      Botrytis cinerea and Penicillium expansum and to select in vivo efficient
      antagonistic strains able to protect fruits against both pathogens at 5 degrees C
      (P. expansum) and 25 degrees C (P. expansum & B. cinerea). Twenty strains of P.
      expansum and ten strains of B. cinerea have been isolated from infected apple
      fruits. Potential antagonistic micro-organisms (thirty three isolates) belonging
      to yeast, bacteria and fungi have been isolated from apple surface. Six of them
      (strains Ach1-1, Ach2-1, Ach2-2 belonging to Aureobasidium pullulans (De Bary)
      Arnaud, and strains 1112-3, 1113-10 and 1113-5 belonging to Aureobasidium
      pullulans (de Bary) Am. v. pullulans) showed a high level of protection (more
      than 80%) at 25 degrees C. once inoculated with P. expansum or B. cinerea for 5
      days. The highest level of protection against P. expansum (96%) was observed with
      the application of Ach 2-1. Six days after inoculation of B. cinerea, strains Ach
      2-2 and Ach 2-1 insured 100% and 96% of protection, respectively. At lower
      temperature (5 degrees C), first symptoms of P. expansum appeared 13 days after
      its inoculation. Percentages of protection observed after apple treatment with
      one of the six antagonistic strains were ranged from 78% to 94% 20 days after P.
      expansum inoculation. Strains labelled Ach showed a protective level higher than
      90% against this pathogen, followed by strain 1113-10 (90%), strain 1113-5 (89%)
      and strain 1112-3 (82%). At 26 days post-inoculation, levels of protection
      decreased but remained higher than 60% (more than 80% with strain Ach2-2 and
      strain 1113-5, 75% with strain Ach2-1 and 1113-10, 72% with ach1-1, 61% for the
      other strains). Strain Ach2-2 and 1113-10 were retained as the best antagonists
      for the subsequent studies.

PMID- 16637170
TI  - Contribution of phlA and some metabolites of fluorescent pseudomonads to
      antifungal activity.
AB  - Fluorescent Pseudomonas species are an important group of PGPR that suppress
      fungal root and seedling disease by production of antifungal metabolites such as
      2,4-diacetylphloroglucinol (2,4-DAPG), pyoluteorin, pyrolinitrin, siderophores
      and HCN. The compound 2,4-DAPG is a major determinant in biocontrol of plant
      pathogens. A 7.2 kbp chromosomal DNA region, carrying DAPG biosynthetic genes
      (phlA, phlC, phlB, phlD, phIE and phlF). Detecting the ph1 genes make them an
      ideal marker gene for 2,4-DAPG-producing fluorescent pseudomonad's. In this study
      we detected ph1A gene (that convert MAPG to 2,4-DAPG) using PCR assay with
      primers phlA-1r and phlA- f that enabled amplification of phlA sequences from
      fluorescent pseudomonad's from ARDRA group 1 and 3. We could detect phlA gene in
      P. fluorescens strains CHAO, Pf-44, Pf-1, Pf-2, Pf-3, Pf-17, Pf-62 and Pf-64,
      native isolates of Iran. The efficacy of this method for rapid assay
      characterizing rhizosphere population of 2,4-DAPG producing bacteria from soil of
      different area of Iran is in progress. We used a collection of 48 fluorescent
      pseudomonas strains in vitro, with known biological control activity against some
      soil born phytopathogenic fungi such as, Macrophomina phaseoli, Rhizoctonia
      solani Vericillium dahlia, Phytophthora nicotiana, Pythium spp. and Fusarium spp.
      and the potential to produce known secondary metabolites such as protease.
      Strains Pf-1, Pf-2, Pf-3, Pf-17, Pf-33 and Pf-44 showed the best antifungal
      activity against all fungi used in this study. Thirty-eight of 48 strains
      produced protease. The ability to rapidly characterize populations of 2,4-DAPG
      producers will greatly enhance our understanding of their role in the suppression
      of root disease.

PMID- 16637171
TI  - Biological control of Botrytis gray mould and Sclerotinia drop in lettuce.
AB  - Research was carried out to evaluate the effectiveness of the biological control
      of two most important fungal diseases of lettuce (Lactuca sativa L.): 1) Botrytis
      Gray Mould caused by Botrytis cinerea Pers. ex Fr.; 2) Sclerotinia Drop caused by
      two pathogenic fungi, Sclerotinia sclerotiorum (Lib.) De Bary and/or Sclerotinia
      minorJagger. Biological control in lettuce was carried out: 1) using Coniothyrium
      minitans Campbell, an antagonist fungus that attacks and destroys sclerotia
      within the soil; 2) identifying lettuce genotypes showing less susceptibility or
      tolerance. The object of this research was to find control strategies to reduce
      chemical treatments. The use of resistant varieties is one of the most economical
      ways to control vegeTable diseases. The lettuce genotypes showing in preliminary
      trials the best behaviour to the sclerotial diseases were compared in a
      randomized complete block experiment design and replicated four times.
      Observations were carried out from February up to April registering the number of
      diseased plants and yield. The pathogens were isolated on PDA medium and
      identified. The isolates grown onto PDA plates, after incubation for 6 weeks,
      allowed obtaining sclerotia that were the target of C. minitans in biological
      control trials. In laboratory, in controlled conditions, 27 small plots (30 cm in
      diameter each) with disinfected soil were performed. In 18 plots 9 sclerotia were
      inoculated (per plot, three of each fungus) and in 9 plots of them a suspension
      of the antagonist fungus was added. Subsequently, three lettuce varieties were
      transplanted. For each variety were compared: 1) untreated plots; 2) treated
      plots with sclerotia only; 3) treated plots with sclerotia and C. minitans
      suspension. The number of diseased plants was recorded. According to symptom
      evaluation scale, ranged from 0 (no disease) up to 10 (100% necrotic leaves or
      dead plants) the plants were grouped into infection classes, calculating the
      McKinney index. In greenhouse trials, "LM 1307" genotype showed less significant
      susceptibility to Botrytis Gray Mould (0-2% of affected plants), while "Ninja"
      and "Charmy" showed 4-11% and 16-26% of diseased plants, respectively. The yields
      were 69.7, 62.7, 55.3 t/Ha, respectively. In laboratory tests, the McKinney index
      gave the following results: no disease in all untreated plants; 38.3, 54.2 and
      89.2% in "LM 1307", "Ninja" and "Charmy" treated with sclerotia only,
      respectively; 2.5, 7.5 and 20.8% in "LM 1307", "Ninja" and "Charmy" treated with
      sclerotia and C. minitans, respectively. In conclusion, the less susceptibility
      of the genotypes to sclerotial diseases and the use of hyperparasites of
      sclerotia of phytopathogenic fungi exhibited best results.

PMID- 16637172
TI  - Biological protection of the main cereals against fungal specific diseases.
AB  - Our field experiments showed that the use of Czech biopreparations (Supresivit,
      Ibefungin and Polyversum) based on the following microorganisms: Trichoderma
      harzianum, Bacillus subtilts and Pythium oligandrum applied as the seed
      treatment, the spray on the plants and like the mixture with mineral fertilizers
      (NPK, ammonium sulphate) lead namely after the seed-treatment and after the
      application as the mixture with mineral fertilizers to the increasing of the
      yield about 3-5 % (spring barley, winter wheat). This increasing was given by
      depression of soil-borne phytopathogenic fungi of the genera: Fusarium,
      Drechslera (Helminthosporium), Pseudocercosporella (Tapesia), Gaeumannomyces, and
      partially Rhynchosporium. The number of the fungi on plant rests were also
      influenced. No effect was observed on smuts and rusts. The smuts needed the seed
      treatment with Vitavax (carboxim, thiram, imazalil) which didn't influence the
      biological treatment with biopreparations. The doses of biopreparations were
      following: the mixture with mineral fertilizer - 0.1 g of biopreparation/ kg of
      mineral fertilizer, the seed treatment - 0.1 g of biopreparation/1 kg of the seed
      and in the spray 0.1 g of biopreparation/1 litre of distilled water. Biological
      biopreparations will be usefull probably also in the future because they don't
      create the harmfull residues. The impact of the biopreparations under different
      ways of soil tillage (conventional variant with ploughing, variants with
      different plant residues and variants without ploughing) was studied as well. The
      influence of different soil preparation on composition of the soil mycoflora and
      the influence on quantity of the pathogenic genera Fusarium, Drechslera and
      others was observed. Quantity of named genera was negatively influenced while
      yield and health status of the plants were influenced positively.

PMID- 16637173
TI  - Optimization of biological control of fungal root diseases in tomato in stonewool
      culture.

PMID- 16637174
TI  - Suppression of Fusarium wilt by combining green compost and Trichoderma hamatum.
AB  - Fusarium wilts, caused by the fungus Fusarium oxysporum, are important diseases
      of horticultural and agricultural crops and lead to significant yield losses. The
      pathogen infects the roots and colonizes the vascular tissue, leading to wilting
      and finally death of the plant. The objective of this study was to investigate
      the efficacy of amendment of green compost and a Trichoderma hamatum strain
      against Fusarium wilt of radish. The substrate effects and the effect of a
      Trichoderma strain were tested in a potting soil bioassay. The tested composts
      lowered the disease level and had a positive influence on the plant yield (fresh
      weight and dry weight). Nothwithstanding, only a small dosis effect of the
      amendment was observed. In the presence of the tested Trichoderma hamatum strain
      no significant lower disease level was observed. Furthermore, a minor effect on
      plant yield (fresh weight and dry weight) was observed compared to the amendment
      with only green compost. Maybe the pathogenic Fusarium oxysporum strain and the
      Trichoderma strain competed for nutrients, iron could be a limiting factor. One
      possible approach to improve biological control may be the application of
      combinations of biocontrol agents.

PMID- 16637175
TI  - Biotic relation between Fusarium oxysporum schlecht. and fungi isolated from the
      substrate of Stewartia pseudocamellia (max.).
AB  - The effect of the fungi community colonizing the substrate of Stewartia plants on
      the growth of Fusarium oxysporum Schlecht. was investigated. The soil samples
      from 2 years old Stewartia cuttings were taken for analysis in the second decade
      of October 2002 and 2003, when the symptoms of disease appeared on Stewartia
      plant. Fungi were isolated from the substrate using the sand method (Manka K.
      1974). Fusarium oxysporum were isolated from root system of Stewartia
      pseudocamellia plant. The isolates selected for the investigation proved
      pathogenic influence on Stewartia in an infection experiment. For estimation of
      biotic effect of saprobiotic fungi community on Stewartia pathogen F. oxysporum
      the biotic series method (Manka K. 1974) was applied. The results showed that
      species of genera: Penicillium and Trichoderma were the most frequent in the
      community of fungi in the substrate. Both fungi communities of these fungi could
      not limit the growth of investigated pathogen F. oxysporum. It showed negative
      ABSTRACT biotic effect. The strongest antagonistic effect displayed Trichoderma
      viride and Trichoderma harzianum.

PMID- 16637176
TI  - Biological control of Tiarosporella phaseolina the causal agent of charcoal rot
      of soybean.
AB  - Charcoal rot caused by Tiarosporella phaseolina (Tassi) Van der Aa is an
      important disease of soybean in Gorgan province of Iran. Experiments were carried
      out with 95 bactenal isolates that were collected from the rhizosphere of soybean
      plant. Among these bacteria only 50 isolates showed antagonistic effect on
      Tiarosporella phaseolina using dual culture test. Six highly effective bacteria
      were selected for subsequent studies. Based on biochemical physiological and
      morphological tests, isolates Pf-12 and Pf-63 were identified as Pseudomonas
      fluorescens, isolates B-13, B-42,B-126 and B-84 as Bacillus subtilis. The
      isolates of P. fluorescens produced antibiotics as well as volatile metabolites
      that inhibited mycelial growth of fungus. Bacillus subtilis isolates inhibited
      the fungal growth through volatile and non-volatile metabolites production. Only
      P. fluorescens isolates produced hydrogen cyanide. In greenhouse studies, the
      isolates B-13 and B-126 reduced 59% and 66% the intensity of charcoal rot of
      soybean respectively. The combinations of isolates B-13 and B-126 were also
      effective on reducing the intensity of disease.

PMID- 16637177
TI  - Activity of plant and mineral oils in the control of Puccinia pelargonii-zonalis.
AB  - Effectiveness of plant oils from corn, olive, rape, soya and sunflower, oils
      recommended for plant protection (Dedal 90 EC, Olejan 80 EC) and mineral oils
      (Atpolan 80 EC, Ikar 95 EC, Olemix 84 EC and Promanal 60 EC) in the control of
      pelargonium rust (Puccinia pelargonii-zonalis) was studied. Oils were applied
      curatively as a plant spray at concentration 1%, 4 times at 7-day-intervals.
      After 4-week experiment more than 11 uredia per leaf were noted on control
      plants. At the same time, on plants protected with oils from olive or soya, Ikar
      95 EC or Olemix 84 EC uredia number decreased at least 50%. The other oils were
      not effective in a suppression of uredia formation. On control plants no uredia
      were destroyed as compared to 11 to 71% destruction on plants protected with the
      tested oils. Oils from olive, soya and also Atpolan 80 EC, Ikar 95 EC, Olemix 84
      EC caused drying off more than 50% uredia. Furthermore, some oils inhibited
      germination of urediospores on PDA medium (potato dextrose agar). Fourteen days
      after the last spraying more than 83% of germinating urediospores were found on
      control leaves. At the same time spores collected from protected plants
      germinated in 17 to 70%. Among tested products oils from rape, corn, sunflower
      and Dedal 90 EC, Ikar 95 EC, Olemix 84 EC were the most effective. In the next
      part of experiment, plants with visible sporulation of P. pelargonii-zonalis were
      sprayed with 1% oils. After 1 and 7 days of incubation, total number of spores
      and number of germinating spores were counted. One day after treatment,
      urediospores collected from leaf blades protected with oils germinated in 20 -
      60%. Oils from olive, corn, Atpolan 80 EC and Ikar 95 EC caused inhibition of
      spore germination at least in 40%. Whereas urediospores from nontreated plants
      germinated in 86%. After 7 days, urediospores collected from untreated plants
      germinated in 65% whereas from plants sprayed with tested oils in 23 - 68%. Oils
      from olive, sunflower and Dedal 90 EC, Atpolan 80 EC were the most effective in
      suppressing urediospores germination.

PMID- 16637178
TI  - Signum, a new fungicide for control of leaf diseases in outdoor vegetables.
AB  - During three years, the new fungicide Signum, containing 6.7% pyraclostrobine +
      26.7 % boscalid and developed by BASF. has been evaluated in leek, carrots and
      cabbages in several outdoor field experiments under practical conditions and
      during one year in outdoor lettuce. In leek, Phytophthora porri is one of the
      major leaf diseases causing lesions on differ ent places on the leaves, resulting
      in at least extra labour costs for trimming or even worse sometimes resulting in
      complete crop loss. So far, crop protection consists of repeated applications of
      fungicides especially during autumn and winter. Pyraclostrobin + boscalid has
      been evaluated in comparison with the fungicides mancozeb, mancozeb + metalaxyl-M
      and azoxystrobin. The progress of the disease during the growth season is
      discussed. For all parameters evaluated, pyraclostrobin + boscalid gave
      comparable or even better results than reference products. Especially during
      2003, a small drop of the activity of benalaxyl against P. porri has been
      observed after repeated applications. In carrots, Erisiphe heraclei and
      Alternaria dauci are both the most common leaf diseases causing yield and quality
      loss. During periods of very high pressure of A. dauci, pyraclostrobin +
      boscalid, applied in a three weeks interval, revealed a superior activity
      compared with triazole references or compared with azoxystrobin. Against E.
      heraclei, a good control but also a clear dose response activity have been
      observed with pyraclostrobin + boscalid. Yield gain was approximately 30 ton /ha
      compared wih untreated. In Brussels sprouts, good efficacy was obtained against
      Mycosphaerella spp., Albugo candida and Alternaria spp. In outdoor lettuce
      Botrytis cinerea and Sclerotinia sclerotiorum are the most important diseases
      causing crop damage and reducing the quality of the heads. Pyraclostrobin +
      boscalid was evaluated in comparison with the standard fungicide iprodione. The
      plant protection was better with the new fungicide pyraclostrobin + boscalid.

PMID- 16637179
TI  - Use of fungicides against powdery mildew during an artificial scab inoculation
      test in an apple breeding programme focused on partial resistance.
AB  - Our project aimed to develop an effective selection methodology for partial
      disease resistance. One of its objectives was to define the optimal selection
      threshold for discarding individual seedlings after artificial scab inoculation
      tests. Working with large populations of seedlings, it was necessary to conduct
      the scab tests at intervals throughout the season, with the risk of powdery
      mildew infection of the young plantlets during the summer. Because Podosphaera
      leucotricha symptoms prevent breeders from properly evaluating scab symptoms, a
      trial was conducted to assess the effect of specific anti-mildew fungicides on
      the results of the scab inoculation test. The results allowed the active
      ingredient and the optimum time for application in relation to the inoculation
      date to be determined.

PMID- 16637180
TI  - Fungicidal activity of some O-acyl chitosan derivatives against grey mould
      Botrytis cinerea and rice leaf blast Pyricularia grisea.

PMID- 16637181
TI  - Fungicidal effect of chitosan derivatives containing an N-alkyl group on grey
      mould Botryti77s cinerea and rice leaf blast Pyricularia grisea.

PMID- 16637182
TI  - Crop protection by seed coating.
AB  - Providence of sufficient and healthy food for increasing human population clears
      the importance of notice to increasing crop production in company with
      environmental loss reduction. Growth and yield of every plant with sexual
      reproduction, depends on germination & emergence of sown seeds. Seed is a small
      alive plant that its biological function is protection and nutrition of embryo.
      Biological, chemical and physiological characteristics of seed, affect on plant
      performance & its resistance to undesirable environmental conditions, and even on
      its total yield. So attention to seed and try to increase its performance is so
      important. One of the factors that cause reduction in germination percentage and
      seedling establishment, is seed disease. It's possible to control these diseases
      by treating the seed before planting it. Coating the seed with pesticides, is one
      of the ways to gain this goal. Seed coating is a technique in which several
      material as fertilizers, nutritional elements, moisture attractive or repulsive
      agents, plant growth regulators, rhizobium inocolum, chemical & pesticide etc,
      add to seed by adhesive agents and cause to increase seed performance and
      germination. Seed coating, leads to increase benefits in seed industry, because
      seeds can use all of their genetic vigor. This technique is used for seeds of
      many garden plants, valuable crops (such as corn, sunflower, canola, alfalfa,...)
      and some of the grasses. In this technique that was first used in coating cereal
      seeds in 1930, a thin and permeable layer of pesticide is stuck on seed surface
      and prevent damage of seedborn pathogens. This layer is melted or splited after
      absorption of moisture and suitable temperature by seed, and let the radical to
      exit the seed. In this approach materials are used accurately with seed,
      evaporation & leakage of pesticide and also adverse effects of some pesticides on
      seeds are diminished, and these factors cause to increase the accuracy and
      performance of pesticide, decrease their consumption, environmental pollution and
      costs. This technique in new and there is a few information about it. So after
      searching and studying about this technique this paper is written to introduce it
      and its applications in crop protection.

PMID- 16637183
TI  - Tolylfluanide + tebuconazole in the control of some ornamental foliage diseases.
AB  - In the control of Sphaerotheca pannosa var. rosae on rose Tolylfluanide +
      tebuconazole (Folicur Multi 50 WG at concentration 0.1%) was used for spray 2 
      times at 14-day-intervals or 4-times at 7-day-intervals. After 4 weeks of plants
      protection effectiveness of tested product was about 75%. In the control of
      Diplocarpon rosae, the product was applied when first disease symptoms appeared
      on rose shrubs. Application was repeated 5-times at 14-day-intervals or 9-times
      at 7-day-intervals. After 9 week-protection effectiveness of tested product was
      about 85% and depended on frequency of sprayings. In the control of Puccinia
      horiana on chrysanthemum, Tolylfluanide + tebuconazole was used as plant spray
      twice at 14-day-intervals or 4-times at 7-day-intervals. After 4 week-protection
      the product suppressed of new telia formation about 55%. Application of the
      product for willow rust (Melampsora epitea) control suppressed formation of new
      uredia about 86% and half of them were dried. In the control of pelargonium rust
      (Puccinia pelargonii-zonalis) the product was used as plant spray 4-times at 7
      day-intervals. It suppressed formation of new uredia about 90% and 1/3 of them
      were dried. It was found that 1 or 7 days after rose spray, spores of D. rosae
      collected from leaf blades only in 6% germinated. Spores taken from nonspraying
      leaves germinated in 90%. In case of P. pelargonii-zonalis, after 1 or 7 days
      after spraying, spores collected from protected plants germinated at 3%, compared
      to 90% on untreated plants. Spores of B. cinerea, collected from protected plants
      germinated at about 10%, whereas on control leaves at 90%.

PMID- 16637184
TI  - The biological evaluation of Zato 50 WG in protection of carrot against
      Alternaria blight.
AB  - Effectiveness of new fungicide Zato 50 WG (biologically active substances BAS -
      trifloxystrobin 50%) in the control of Alternaria blight on carrot was studied.
      Field experiments were carried out in the years 2003-2004 on carrot cv. Koral. As
      the standard fungicide Amistar 250 SC (BAS - azoxystrobin 250 g/dm3) was used.
      The results of health status of carrot leaves analysis in first and second year
      of experiment showed, that development of disease symptoms was lower on leaves of
      chemical protected plants than on leaves of control plants. The last estimation
      of infestation degree of carrot leaves made immediately before harvest showed,
      that standard fungicide Amistar had longer systemic influence on plants. This was
      confirmed the lower (statistically significant) infestation index of protected
      carrot in combination with Amistar. The estimations of health status of carrot
      roots were made directly after digging up indicate, that there wasn't difference
      of value of infestation index between protected combination and control.
      Experiment showed, significant effect of tested fungicides on crop quantity of
      carrot roots per 1 m2. Especially in the second year of study the crop of carrot
      roots in combination with Zato was higher - statistically significant - than in
      the rest combinations.

PMID- 16637185
TI  - Potato late blight in Morocco: characterization of Phytophthora infestans
      populations (virulence and mating type).
AB  - Late blight caused by Phytophthora infestans, is the most important disease of
      potato in Morocco. Use of partially resistant cultivars should be an essential
      component of a sustainable management strategy of potato late blight, provided
      the durability of this form of resistance. It is therefore important to determine
      the nature of P. infestans Moroccan populations. Mating types were determined for
      91 strains of P. infestans collected in the northern (Larache-northern plain),
      north western (Kenitra) and north eastern (Meknes, Middle Atlas) potato cropping
      areas of Morocco in 1999-2000, 2000-2001 and 2003-2004. They showed a clear
      regional structure of these populations, with the presence of both mating types
      (A1 and A2). Of all isolates collected since 1999, A2 mating type constituted 56%
      (54 isolates), following by A1 mating type (40.7%, 31 isolates) and A1-A2 (self
      fertile) mating type (3.30%, 3 isolates). Populations from Meknes and Kenitra
      consisted mainly of A2 mating type, whereas populations from Larache
      predominantly included A1 mating type. Physiological race study revealed the
      presence of 19 races of P. infestans in the first collection of 25 isolates
      tested between 1999 and 2001. All known virulence genes were detected in western
      and northern Moroccan isolates, except virulence for resistance genes R2, R5, and
      R6 which were absent. All isolates were able to overcome two or more R genes
      except one isolate (5-1) corresponding to race 1.

PMID- 16637186
TI  - A molecular investigation to identify phytoplasmas associated with fruit trees.

PMID- 16637187
TI  - Surveys of new and rare microfungi in the Dusseltal (North Rhine-Westphalia)-
      Germany.
AB  - In the years 2003 and 2004 we have observed an about 70 hectare large area in the
      Dusseltal, the eastern part of the Neandertal in North Rhine-Westphalia. There we
      collected on trees, bushes and herbs and found about 150 microfungi of which some
      are new for Germany or the entire world. E.g.: Pseudocercospora populigena N. ALE
      AGHA, U. BRAUN & G.B. FEIGE on Populus berolinensis; Vialaea insculpta (FR.)
      SACC. on Ilex aquifolium L.; Passalora amelopsidis (PECK.) U. BRAUN on
      Parthenocissus quinquefolia (L.) PLANCH.: Pleiochaeta setosa (KIRCHN.) HUGHES on
      Genista angelica L.; Cercospora mercurialis PASS. on Mercurialis perennis L. (new
      for NRW); Pleurocytospora vestita PETRAK on Ribes aureum PURSH.; Gonatobotrys
      simplex CORDA on Lolium perenne L.; Phomatospora berckleyi SACC. on Dactylis
      glomerata L. and so on. All specimens are located in the Herbarium ESS, Mycotheca
      Parva collection G.B. Feige & N. Ale-Agha.

PMID- 16637188
TI  - New, rare and remarkable records of microfungi from the Slovakian Republic.
AB  - During an excursion to the Slovakian Republic (lower and upper Tatra) of the
      Botanical Institute of the University of Essen in 2004 we were able to collect
      about 150 species of microfungi as parasites or saprophytes on cultivated crops
      and wild plants. Some of them are new for the entire world and a few of them are
      new for the Slovakian Republic, e.g: Ramularia liliicola N. Ale-Agha, U. Braun &
      G.B. Feige on Lilium martagon L.; Septoria aegopodii DESM. Ex Kickx. F. on
      Aegopodium podagaria L.; Puccinia asarina Kunze on Asarum europaeum L.; Puccinia
      polygoni ALB. & SCHW. and Puccinia polygoni-amphibii PERS. on Bilderdykia
      convolvulus (L.) Du Mont.; Ramularia chamaenerii Rostr. and Mycosphaerella
      chamaenerii Saville on Epilobium angustifolium L.; Plasmopara pusilla (de By.)
      Schroet on Geranium sylvaticum L.; Cercosporidium depressum (Berk. & Br.) Deighta
      on Angelica sylvestris L. All specimens are located in the Herbarium ESS,
      Mycotheca Parva collection G.B. Feige & N. Ale-Agha.

PMID- 16637189
TI  - Aflatoxin contamination of developing corn kernels.
AB  - Preharvest of corn and its contamination with aflatoxin is a serious problem.
      Some environmental and cultural factors responsible for infection and subsequent
      aflatoxin production were investigated in this study. Stage of growth and
      location of kernels on corn ears were found to be one of the important factors in
      the process of kernel infection with A. flavus & A. parasiticus. The results
      showed positive correlation between the stage of growth and kernel infection.
      Treatment of corn with aflatoxin reduced germination, protein and total nitrogen
      contents. Total and reducing soluble sugar was increase in corn kernels as
      response to infection. Sucrose and protein content were reduced in case of both
      pathogens. Shoot system length, seeding fresh weigh and seedling dry weigh was
      also affected. Both pathogens induced reduction of starch content. Healthy corn
      seedlings treated with aflatoxin solution were badly affected. Their leaves
      became yellow then, turned brown with further incubation. Moreover, their total
      chlorophyll and protein contents showed pronounced decrease. On the other hand,
      total phenolic compounds were increased. Histopathological studies indicated that
      A. flavus & A. parasiticus could colonize corn silks and invade developing
      kernels. Germination of A. flavus spores was occurred and hyphae spread rapidly
      across the silk, producing extensive growth and lateral branching. Conidiophores
      and conidia had formed in and on the corn silk. Temperature and relative humidity
      greatly influenced the growth of A. flavus & A. parasiticus and aflatoxin
      production.

PMID- 16637190
TI  - Armillaria mellea as a cause of oak decline in Hatam-baigh forest of Iran.
AB  - A200 ha forest of "Hatam-baig" is located in Ardebil Province on the Northwest of
      Iran. Oak trees (Quercus macranthera Fisch & Mey) in this forest have been faced
      with declining and extinction since 1991, that has destructed about one third of
      the forest trees until now. This disorder was expressed in various symptoms
      including wilting, defoliation and decline. In order to identify factors causing
      decline, a study was managed from 1998 to 2001. Samples were taken from roots,
      trunks, crowns and soil beneath the canopy and were cultured on different culture
      media subsequently. Armillaria mellea (Vahl) P. Kumm., Phytophthora cryptogea
      Pethybr. & Laff., Dematophora sp., Pythium aphanidermatum (Edson) Fitzp. and
      Fusarium spp. were the most common isolated fungi. A. mellea appeared to be the
      essential causal agent of the decline according to the studies made on oak tress
      decline around the world and based on brown rot observed beneath mycelial fans in
      the cross section prepared from the trunk and characteristics of the isolated
      fungi. The fungus activity had been favored by physiological weakness and
      stresses in oak rootstocks caused by brown- tail moth (Euproctis chrysorhoea L.)
      and drought stress in infected trees. The biological species of this fungus was
      identified as Armillaria mellea, using hybridization tests and application of
      haploid test strains. The fungi such as Phytophthora sp., Pythium sp., and
      Dematophora sp. can not be infective in this forest due to being hydrophylous. In
      the southern part of the forest with remarked steepness, the severity of the
      decline appears to be more than that in the smoothly northern part. The decline
      of Q. macranthera is reported as matrix nova. The report of the isolated fungi
      from this oak species is also universally new.

PMID- 16637191
TI  - Pathogenicity of two species of Fusarium on some cultivars of bean in greenhouse.
AB  - Twenty isolates of Fusarium oxysporum and F. solani were isolated from the
      infected roots of bean in different farms of east Azarbaijan and Tehran Provinces
      and their pathogenicity determined. Most isolates of the fungi were identified as
      F. oxysporun. They caused root rot, yellowing and wilting of bean in the field.
      In this test, the roots of 6 cultivars of bean seedlings soaked in suspension of
      the 7 isolates of the fungi (a1, Gogan, a2, Bilverdi, a3, Savojbolagh-Hashtgerd,
      a4, field of Agr. Coll. a5, Khomein, a6, Ramjin of F. oxysporum and a7 of F.
      solani of Varamin, Iran) for 5 minute (106 spores/ml.) then transplanted into the
      sterilized soil in 4 pots (as replication). For control (a8) the roots soaked in
      distilled water. The results showed that percentage average of necrotic roots and
      crowns of isolates al, a2, a3, a5, a6, a7 was %20.31 in group a, a4 was %43.52 in
      group b and a8 was %2.77 in group c after 3 weeks. The isolate a4 (from the field
      of Agricultural College, Karaj) was more infectious than the other because it
      caused wilting, yellowing the leaves and decreased the growth very soon, followed
      by a5 with %25.32 rate was more pathogenic. Bean cultivar Goli-Red was more
      tolerant with %10.02 than the others of 16.29 (Naz Red) to 25.15 percent of
      necrotic the roots & stems.

PMID- 16637192
TI  - Study on genetic diversity of Magnaporthe grisea using PCR and determination of
      the mating type alleles distribution in Mazandaran province, Iran.
AB  - The population structure of Magnaporthe grisea, the causal agent of the rice
      blast, was analyzed in Mazandaran province, using DNA fingerprinting based on
      RAPD-PCR by means of three primers including "I", "D" and "H". Total DNA of 47
      isolates was extracted and amplified according to a specific PCR program. As a
      result, variable length fragments were generated. Each isolate was subjected to
      DNA fingerprinting and clonal lineages were determined. Phenetic analysis
      differentiated three distinct fingerprint lineages. In order to study on
      fertility status and distribution of the mating type idiomorphs (alleles), 72
      monoconidial isolates from Mazandaran province were paired with four standard
      fertile hermaphrodite isolates. The mating type of 36 isolates was determined as
      Mat 1-1. The others (36 isolates) did not form any perithecia in pairing with
      standard isolates

PMID- 16637193
TI  - Susceptibility of six cultivars of bean to different isolates of two species of
      Fusariumin greenhouse.
AB  - In greenhouse, susceptibility of 6 cultivars of bean (b1, green bean cv.
      contender, b2, Pinto b. cv. Cos-16, b3, green b. Sun Ray, b4, white b. cv.
      Daneshkadeh, b5, red b. cv. Naz, b6, red b. cv. Goli) evaluated to 7 isolates of
      2 species of Fusarium (6 isolates of F. oxysporum and 1 isolate of F. solani from
      Varamin, Iran) in 4 pots (as replications) in factoriel experiment. The seedlings
      of each bean cultivars soaked in a suspension of the fungi (106 spores/ml.) for 5
      minutes and transplanted into the pots contained sterilized soil, for control,
      the roots soaked in distilled water. After 35 days of inoculating and
      transplanting in greenhouse conditions (with 18-26 degrees C and 12 h light & 12
      h dark) the percentage of necrotic roots and stems of the seedlings affected to
      the isolates of the fungi, also height and weight of them in different treatments
      datermined and calculated. The results showed that, the average of necrotic
      percent of the cultivars of bean seedlings grouped in 3 category (b1, b2, b3, b4
      with 25.15% in group a and b5, red bean cv. Naz with 16.29% in group b and b6 red
      bean cv. Goli with 10.02% in group c) based on cluster analysis. But by Dunken
      method the infection set on 5 groups as respectively b4, 28,72% (a), b2, 25.83%
      (ab), b1 & b3, 23,18% & 22.84% (b), b5, 16.29% (c) and b6, 10.02% (d). So, red
      bean cv. Goli was more resistant and white bean cv. Daneshkadeh was more
      susceptible than of another cultivars, but averse the effect of the fungi on
      growth factors were different.

PMID- 16637194
TI  - The causal agents of damping-off disease of buglosse from Iran.
AB  - Iran is considered a major genetic for medicinal plant in the world. Because of
      this significant diversity and historical background in identification and
      utilization to remedy human and animal diseases, export of medicinal plant can
      help to strengthen local as well as natural economy. Buglosse (Fig. 1) is one of
      the most important and common medicinal plants in Iran and exist as Echium
      amoneum and Borago officinalis. This work was conducted in order to identify the
      causal agent(s) of damping off disease in buglosse. Plant disease samples were
      taken from Esfahan and Tehran provinces. Symptoms on original plant including
      root, crown rot, dark tissue, pith and hallow root were collected in order to
      isolate disease agent(s). Symptomatic root and crown tissues after surface
      sterilization with 96% ethanol were transferred on to PDA and WA media and also
      on moist filter paper in petri dishes. Two fungal colonies grew from tissue
      segments and spore culture was subsequently purified. The fungal isolate
      identified as Rhizoctonia solani based on the following test. Hyphal tip was
      removed from colony margin placed on PDA and PSA media and incubated in dark.
      Colony diameter of one hundred hyphae measured and nucleus was stained according
      to Bandoni (1979), Kronland and Stanghellini (1988). It was observed that in each
      cell of hyphae there are more than two nuclei. Single spore culture were obtained
      from macroconidia of Fusarium isolate. After 24 hr of incubation, growing single
      spore were transferred to KCL medium to detect spore chains. Fungal isolates
      transferred to PSA and PDA media for sporulation. After 7 days colonies appeared
      as white cream to pinkish on top and cream to dark pink at the bottom of petri
      dish with abundant micro and macro conidia. Colonies were snow white, felting
      shape, with ample causal hyphae on PSA medium. On KCL medium, fungal growth was
      superficial and colonies were colorless with long macroconidia and individual
      sausage-shape macroconidia being thinner one side and having maximum four septa.
      Microconidia were long double compartment round on both side, straight to
      slightly curved. Base on morphology and dimension of conidia and production of
      chlamidospore the funguses identify as Fusarium solani.

PMID- 16637195
TI  - Vegetative compatibility and pathogenecity of Verticillium dahliae kleb. isolates
      from olive in Iran.
AB  - Verticillium wilt caused by Verticillium dahliae is a serious problem of olive
      trees leading to significant reduction in yield. Verticillium wilt of olive trees
      was first recorded in Iran 1996 and confirm as due to Verticillium dahliae Kleb.
      101 isolates of V. dahliae from olive trees at deferent locations in north
      provinces of Iran were assigned to vegetative compatibility groups (VCGS), using
      nitrate non-utilizing (Nit) mutants. A higher frequency of nit 1/nit 3 mutants
      (93%) was obtained compared with NitM (7%) with 10% of the isolates being
      assigned to VCG1 and 51% VCG4B and 19% VCG2A. 20% of isolates could not be
      classified in standard isolates. The pathogenecity of 15 randomly selected
      isolates (5 of each VCG) was tested on olive seedling (cv. Zard) and eggplant.
      The VCGs isolates were similarly aggressive on olive. However, VCG1 isolates were
      more aggressive on eggplant cv. Local than the VCG2A and VCG4B isolates as
      indicated by a higher colonization index. The pathogenecity tests of the pathogen
      on test plants (cotton cv. 'sahel', eggplant cv. 'local' and tomato cv. 'ps')
      show all isolates category in 2 pathogenecity groups defoliate and non-defoliate
      (with severe and mild subgroups). The morphology of V. dahliae isolates on
      C'zapeck's agar and water agar medium were different especially for
      microsclerotia appearance time in culture and their morphology.

PMID- 16637196
TI  - Study on DNA diversity of Iranian populations of Erysiphe betae causal agent of
      sugar beet powdery mildew.
AB  - 107 samples of E. betae were collected on infected leaves from all over Iranian
      beet cultivation areas. Their choosing were based on geographical and host
      origin(sugar beet, red beet, fodder beet and wild beet). 30 isolates were single
      colonized and grown on sugar beet susceptible genotype 7233. 107 specimens were
      analyzed by restriction fragment length polymorphism (RFLP) of the ribosomal
      internal transcribed spacers (ITS) and 5.8s DNA which previously amplified by the
      polymerase chain reaction (PCR) with 2 universal primers, ITS1 and ITS4. PCR
      product was affected by 9 different restriction enzymes. PCR product was a 645 bp
      band for all of the isolates. 3 restriction enzymes; CfoI, MspI and HaeIII could
      cut this fragment into smaller bands, but electrophoretic patterns were identical
      for all of the isolates. 30 single colonized isolates were used in RAPD
      experiments. In RAPD-PCR experiment genetic diversity was investigated with 30
      isolates from different parts of the country. 59 random primers were used and
      then 21 primers that displayed good consistency and reproducibility were
      selected. Most of the primers revealed identical patterns between 3 to 14 bands.
      5 primers that showed more polymorphism were selected to analyze 30 isolates. For
      these 5 primers 61 distinct bands were obtained which 62% of these bands were
      polymorphic. Results indicated that there is no relationship between cluster
      grouping and geographical origin and the isolates showed a high similarity.

PMID- 16637197
TI  - Study on the overwintering of cleistothecia and conidia of Erysiphe betae causal
      agent of sugar beet powdery mildew in Iran.
AB  - Sugar beet leaves covered by sexual (cleistothecia) and asexual forms (mycelia
      and conidia) of Erysiphe betae were gathered at harvest time and maintained under
      natural outdoor conditions. In order to determine the function of cleistothecia
      and also conidia in the overwintering of E. betae some experiments were
      performed. The results showed that ascospores were unable to be released in petri
      dishes but their release under natural conditions occurred after 4 months. Under
      In vitro conditions ascospores did not germinate but on the leaves germination
      was rarely possible, however these ascospores were degraded after 7 days and
      didn't have pathogenicity. Conidia could induce pathogenicity after 3 but not 4
      months. The period after inoculation until appearance of disease symptoms
      increased with aging of conidia. The results for conidial germination showed that
      fresh conidia had 80 percent germination on glass slides but it decreased sharply
      after 2 weeks and reached to 0 percent after 4 weeks. Although their germination
      on the leaves was not more than 46 percent of fresh conidia but they had good
      germination after 2 and 4 weeks. The results for the experiment to observe the
      first appearance of the disease in the field suggested that the first conidia
      were trapped by spore-trap in early June and the first symptoms appeared 20 days
      later. The conclusive results showed that ascospores had no function in the
      survival of the fungus and air-borne conidia are the main source of primary
      infections.

PMID- 16637198
TI  - Treatments with gras compounds to keep fig fruit (Ficus carica L.) quality during
      cold storage.
AB  - The trade of fresh fig fruit is restricted by its high perishability and numerous
      attempts have been done to extend the postharvest life. The main difficulties can
      be found in the fast ripening and the easiness of pathogen spread. Although the
      ripening can be slowed by low storage temperatures (close to 0 degrees C) the
      control of pathogens remains still unsolved since no pesticide treatments are
      allowed. Generally Recognized As Save Compounds (G.R.A.S.) are possible
      candidates to fulfil this void. Sodium carbonate (SC) solutions (0.5, 1, 2 and
      3%) and acetic acid (AAC) vapours (25, 50 and 100 ppm) have been used as
      postharvest treatments to control Botrytis cinerea on black (Craxiou de Porcu)
      and white (Rampelina) fig varieties. Fruit was subsequently stored at 2 or 8
      degrees C and 90% relative humidity for two weeks. At the end of the experiment
      decay, weight loss, pH, acidity, total soluble solids and visual assessment were
      performed. SC treatment at 1% reduced significantly the decay while, lower and
      higher concentrations did not. Between the two studied varieties the lowest decay
      percentage (9.8%) was found for the Craxiou de Porcu. Using AAC a good efficacy
      was achieved only with 100 ppm, this treatment decrease to 2.4% the incidence of
      decay irrespective to storage temperature. Lower concentrations were lesser
      effective and the efficacy was strictly dependent on the storage temperature,
      being higher at 2 degrees C. No treatment damages were observed following SC or
      AAC applications. Regarding fruit weight loss all treatments did not affect this
      parameter that was 10.1% and 16.9% at 2 and 8 degrees C, respectively. Chemical
      analyses performed at the end of the storage period did not evidenced differences
      among the treatments and slight ones if compared to initial values. Visual score
      of the fruit at the end of storage evidenced a better keeping quality for Craxiou
      de Porcu especially when stored at 2 degrees C. Both G.R.A.S. compounds are
      promising, but in the reported experiments AAC was the most effective.

PMID- 16637199
TI  - Infection rates of perennial ryegrass seeds (Lolium perenne L.) with different
      fungi.
AB  - Authors made investigations to map occurrence of different fungal pathogens on
      seeds of varieties from different grass species. This work presents data on three
      cultivars of perennial ryegrass (Lolium perenne L.). When seeds were germinated,
      eight genuses of fungi were identified belonging to the Deuteromycota. Alternaria
      was the most frequently occurred genus. Drechslera, Bipolaris, Cladosporium,
      Stemphylium, and Epicoccum spp. has also been found in the seed samples. Two
      genus of fungal pathogens (Embellisia and Septonema) were identified which were
      not mentioned in Hungary so far.

PMID- 16637200
TI  - Comparison of health status between organic and conventional products.
AB  - This paper reports the results of two trials carried out to estimate the hygienic
      sanitary status of samples obtained from organic farming in comparison with
      products obtained from conventional agriculture. In three years of activity were
      carried out analyses on samples of common or durum wheat and on processing
      products like. flour, bran, macaroni and bread obtained from biological and
      conventional method. Also samples of vegetables and fruits were analyzed. The
      laboratory analyses have been focalized on qualitative and quantitative
      evaluation of fungal contamination and surveying of pesticide residues level. The
      great size of collected data has not highlighted substantial differences between
      the two analyzed typologies. About pesticide residues levels, generally they
      proved to be contained under the Italian legal limit, so both these products can
      be considered healthy under a hygienic-sanitary profile. The trials should be
      extended also to other cultivations like herbs, fruit-trees and vegetables to
      improve our knowledge's about qualitative and hygienic differences beyond the two
      methods of production and defense.

PMID- 16637201
TI  - Carbonic acid salts at 25 or 45 degrees C to control loquat decay under shelf
      life conditions.
AB  - Generally recognised as save compounds (G.R.A.S) are attractive substitutes to
      synthetic chemicals in postharvest control diseases. They meet safety
      requirements, are cheap and able to be integrated with other disease control
      technologies. Among G.R.A.S compounds, carbonic acid salts have been investigated
      on carrots, bell pepper, melons, sweet cherries and their efficacy was also
      evaluated when combined with biological control agents. Moreover, the possibility
      to use sodium carbonate and sodium bicarbonate to prevent P. digitatum an P.
      italicum spread on Citrus fruit was studied since the begin of the 20th century.
      We explored the possibility to extend the use of carbonate-bicarbonate salts on
      loquat fruit in order to control the pathogens and to extend postharvest life.
      Loquat is a very perishable fruit, susceptible to decay, mechanical damage,
      moisture and nutritional losses during its postharvest life. We tested the
      combined effect of temperature and sodium or potassium carbonate-bicarbonate and
      ammonium carbonate. The fruit was dipped in the salt solutions at variable
      concentrations (0.5, 1 and 2% w/v) at 25 or 45 degrees C for two minutes and than
      stored under shelf life conditions (25 degrees C and 70% RH). Decay, weight loss,
      pH, titrable acidity and sugar content were detected after twelve days.
      Preliminary data show that the combined treatments were effective in decay
      control depending on salts. Best results were obtained with 2% potassium and
      sodium carbonate solution at 25 degrees C. Weight losses were related to
      treatment temperature and salts concentrations whereas, no differences were
      detected in the chemical parameters compared to the control.

PMID- 16637202
TI  - Grapevine downy mildew control in organic farming.
AB  - Cupric products at low dose and alternative compounds have been tested to control
      the downy mildew in an organic vineyard. It has found that copper compounds
      control downy mildew in a satisfactory way, reducing, at the same time, the dose
      of copper metal. The alternative products were not satisfactory to control
      Plasmopara viticola.

PMID- 16637203
TI  - Reaction of selected soybean cultivars to Rhizoctonia root rot and other damping
      off disease agents.
AB  - Eight soybean cultivars; Giza 21. Giza 22, Giza 35, Giza 82, Giza 83, Crawford,
      Holladay and Toamo were evaluated to Rhizoctonia root rot using agar plate and
      potted plant techniques. Data cleared that, in agar plate assay all soybean
      cultivars were moderately susceptible (MS), although the differences between them
      were significant (P=0.05). Generally, in potted assay, the reactions were
      resistant (R) or moderately resistant (MR) to root rots. Also, the differences
      between cultivars were significant (P=0.05). These cultivars were inoculated
      under greenhouse conditions with Fusarium solani, Macrophomina phaseolina,
      Rhizoctonia solani and Sclerotium rolfsii Generally, G21 had the least pre
      emergence damping-off followed by Giza 35, Crawford and Giza 83 with averages of
      19.0, 20.0, 20.5 and 21.5%, respectively. In case of post-emergence, Giza 35 had
      the least values, followed by Giza 21, Crawford and Giza 82 with averages 3.95,
      4.10, 4.10 and 4.25%, respectively. Under naturally infested soil in the field
      conditions the reactions of the same cultivars to damping-off were evaluated in
      two successive seasons. In 2002 season, G35 had the least pre-emergence damping
      off % followed by Giza 21 and Giza 22 with averages of 22.61, 24.33 and 29.33%,
      respectively. Also, G35 had the least post-emergence damping-off % followed by
      Toamo and Giza 21 with averages of 9.40, 10.33 and 10.41%, respectively. In 2003
      season, the same trend was appeared with light grade where Giza 35 had the least
      pre-emergence damping of % followed by Giza 22 and Giza 21 with averages of
      30.67, 31.00 and 36.67%, respectively and Giza 35 was the most resistant cultivar
      against post-emergence damping-off, followed by Giza 21 and Giza 22 with averages
      of 10.91, 11.32 and 11.80%, respectively. Generally, Giza 21 significantly
      surpassed the other cultivars in plant height, number of pods per plant and 100
      seed weight. Moreover, also it had second grade with the other traits.

PMID- 16637204
TI  - Biological and physical approaches to improve induced resistance against green
      mold of stored citrus fruit.
AB  - Health and environmental concerns have point out the need to improve or change
      several manufacturing steps in the food chain. In this context particular
      attention should be given to the technologies involved in fruits and vegetables
      production. Nearly all fresh fruit and vegetables are subjected to different
      periods of storage and/or shelf-life before of their consumption. This implies
      the need to protect the commodities from microbial spoilage. Some Citrus species
      (e.g. lemon and grapefruit) may be stored for several months before consumption
      and then post-harvest treatments are essential to contain green (Penicillium
      digitatum) and blue (P. italicum) moulds. Alternative approaches to chemicals
      usually have a lower efficacy in containing rots but fulfill the consumer's
      expectation. Among the alternative strategies, the improvement of host natural
      resistance is promising. In this regard, we report some results concerning the
      use of biotic (yeast) and abiotic agents as inducers of phytoalexin (i.e.
      scoparone and/or scopoletin) accumulation in Citrus rind and its importance in
      the control of fungal decay. In all experiments the inducers were applied on
      fruits before or 24 h after inoculation with P. digitatum and the rot severity
      was monitored 7 days later. The accumulation of phytoalexins was monitored
      according to a standard methodology by HPLC. In all experiments a positive
      correlation was found between increase of the phytoalexin scoparone in host
      tissue and reduction of decay.

PMID- 16637206
TI  - Detection of Alfalfa mosaic virus (AMV) in pea field in Iran.
AB  - During the spring and summer, in 2003-2004, pea viruses were identified in twenty
      pea fields of Tehran. Some leaf samples were collected randomly from pea fields
      of Tehran. Samples were tested by Double Antibody Sandwich Enzyme Linked
      Immunosorbent Assay (DAS-ELISA) technique using polyclonal antiserum of Alfalfa
      mosaic virus (AMV), AS-0001, DSMZ, Braunschweig, Germany). The samples were
      extracted in 0.1 M Phosphate buffer pH 7 to 7.5 and inoculated on Chenopodium
      amaranticolor, Chenopodium quina, Phaseolus valgaris, Vicia faba, Vignia
      unguiculata. Pea cultivars were infected by AMV, causing mild mosaic, translucent
      veins and a diffuse green-yellow of tender parts and spots may also was involved
      necrosis of tissue. Infected plants grow slowly and malformed pods produce fewer
      ovules. In Chenopodium amranticolor, C. quina chlorotic and necrotic flecks, and
      Vicia faba systemic mosaic had produced. Phaselous vulgaris and Viginia
      unguiculata are good assay hosts for strains that produce local lesions after 3-5
      days in these plants. Back inoculated on Pisum sativum and Vicia faba and tested
      with DAS-ELISA that had been confirmed the results. This is the first report of
      AMV on pea from Iran.

PMID- 16637205
TI  - Chitinase gene transformation through Agrobacteriumand its explanation in soybean
      in order to induce resistance to root rot caused by Rhizoctonia solani.
AB  - Chitinase gene (chi) of bean which has been cloned in recombinant binary plasmid
      vector, pBI121 with 35s promoter of Cauliflower mosaic virus (CaMV), were used
      for transformation of soybean using strain LBA4404 of Agrobacterium. The plasmid
      contained nptII gene that is a resistant gene to kanomycin as selector marker and
      Gus gene as reporter. Cotyledon explants of Williams and Clark cultivars were
      inoculated by Agrobacterium suspension with pBI121 and were cultured in
      regeneration medium. After complete regeneration of explants to seedling in B5
      medium amended with kanomycin, polymerase chain reaction analysis were conducted
      to ensure conjugation of nptII, Gus, CHN genes in transformants seedling of
      soybean. Results showed that some lines of soybean contained Gus and CHN genes.
      More ever, chitinase activity in leaf extract of transformed soybean lines was
      significantly more than untransformed soybean, exception one sample. Bioassay of
      chitinase activity of transgenic lines on in vitro condition prevented mycelial
      growth of Rhizoctonia solani in comparison with untransformed control leaf
      extract.

PMID- 16637207
TI  - First report of occurrence of two viruses on pea field in Iran.
AB  - An intensive survey was conducted to identify virus diseases affecting pea crops
      in Tehran province of Iran. A total of 270 pea samples were collected randomly
      from pea fields. samples were tested by Double Antibody Sandwich Enzyme Linked
      Immunosorbent Assay (DAS-ELISA) using polyclonal antisera prepared against PSBMV
      (AS-0129, DSMZ, Braunschweig, Germany) and TSWV (AS-0580, DSMZ, Braunschweig,
      Germany). Virus disease incidence in pea samples was followed by PSBMV (33%) TSWV
      (24.4%) and PSBMV+TSWV (17.77). The positive samples with PSBMV were extracted in
      0.05M phosphate buffer pH 6.5-7 containing 2% pvp and inoculated on Pisum
      sativum, Vicia faba, Chenopodium quinoa, Chenopodium amaranticolor. That produced
      in Pisum sativum; leaflets roll downwards, shoots curl, internodes shorten and
      plants are rosetted. Early infections reduce flower and fruit formation or
      eliminate their development. Broad bean has symptoms accompanied by a certain
      margin rolling and leaflet distortion. In Chenopodium amaranticolor necrotic
      local lesions and Chenopodium quinoa chlorotic local lesions had produced. The
      positive samples with TSWV were extracted in 0.01 M phosphate buffer containing
      1% Na2 SO3 and inoculated on Petunia hybrida, Pisum sativum. TSWV causes several
      symptoms in infected peas, including brown leaf petiole and stem coloration,
      leaflet spotting, vein necrosis. In petunia hybrida after approximately 5 days
      showed local necrotic lesion. Biological purification in TSWV with chlorotic
      local lesions in Petunia hybrida and in PSBMV; chlorotic local lesions in
      Chenopodium quinoa were done. In PSBMV, back inoculated on Pisum sativum and
      Vicia faba also tested with DAS-ELISA. RT-PCR confirmed the results. This is the
      first report of PSBMV and TSWV naturally infecting pea in Iran.

PMID- 16637208
TI  - Identification of PVY-N on potato and tobacco in Tehran and Mazandaran provinces.
AB  - During two growing seasons in years of 2003 and 2004 potato and tobacco of virus
      infected plants were collected from fields in Tehran (Damavand) and Mazandaran
      (Behshahr) provinces. Serological methods of TAS-ELISA and DIBA were performed by
      using PVY antiserum (DSMZ - Plant Virus Collection; Germany) but only PVY was
      detected. The strain of samples was determined by using MAb of potato virus Y (AS
      0403/1; DSMZ; Germany). The molecular weight of the virus coat protein was
      approximately 34 kDa in SDS-PAGE and Western blotting. Total RNA was extracted
      for RT-PCR. Immunocapture RT-PCR and RT-PCR products were 974 bp by using
      specific primers of PVY. IC-RT-PCR has given the best results.

PMID- 16637209
TI  - Occurrence and physico-serological properties of potato virus S (PVS) in Iran.
AB  - 1818 collected samples of potato plant showing virus infection symptoms from 85
      fields were tested for PVS infection using DAS-ELISA. Average of infection to
      this virus varied from 0 to 100%. Least infection was belonging to fields with
      new introduced varieties. On the other hand native and old introduced cultivars
      showed heavy infection. In field condition, PVS infected plants didn't show very
      obvious symptoms, so some infected plants may be missed in field sample
      collecting. The physical properties of 3 isolates, Avaj, Stanboly and Agria No 15
      were determined. TIP 55-60 degrees C, DEP 10(-3) and Liv measured 3-4 days.
      Ouchterlony agar double diffusion test using SDS was useful for virus detection
      and precipitation lines didn't show any spur between isolates, although isolates
      differs slightly in symptomatology. SDS-Page and Western blotting methods used
      successfully for virus detection and determining and measuring viral protein
      components.

PMID- 16637210
TI  - Purification of potato virus X and preparation of its antiserum.
AB  - Potato virus X (PVX) isolated from the potato leaf and tuber samples which were
      collected from various fields in Damavand and Ardabil. The initial isolations of
      the virus were made from potato by mechanical inoculation on Gomphrena globosa L.
      and Chenopodium spp. that produce local lesion, and then it causes mosaic on
      Nicotiana spp. and Datura stramonium L. An isolate of the virus inoculated to
      Nicotiana glutinosa L. and it was maintained throughout the work. Sap from
      infected N. glutinosa was ineffective after dilution to 10-6, 10 minutes at 70
      degrees and 10 weeks at room temperature. The virus was readily purified from
      infected leaves and the best protocol was Moreira & Jones 1980 than the other 2
      methods of Fribourg 1975 and Shepard & Shalla 1972. Antisera were prepared
      against native, degraded proteins and micro precipitin test showed that both
      antisera had a 1/512 titer. Precipitin lines with D - Protein antiserum was
      better of the native protein antiserum in agar double diffusion test than treated
      with SDS. The isolate of the virus was not transmitted by none of 2 species of
      Cuscuta but transmitted from infected leaves to healthy plants with sap
      inoculation without using Carburandum. This isolate showed positive reaction with
      gamaglubulin in kate received from CIP centre.

PMID- 16637211
TI  - Determination of the races of potato virus X and its host rang in Karaj, Damavand
      and Ardabil, Iran.
AB  - Potato virus x (PVX) is found commonly in potato-growing areas, worldwide. It is
      an economically important virus which causes losses in tuber yield of approximate
      5 to 15 percent. In a 2 year survey, potato leaf and tuber samples were collected
      from various fields in Damavand and Karaj. The initial isolations from potato
      were made by mechanical inoculation first to Gomphrena globosa L. and later to
      Dartura stramonium L. It was not transmitted by 2 species of Cuscuta but
      transmitted mechamically. The isolates were inoculated to Nicotiana glutinosa L.
      in which they were maintained throughout the work. Sap from infected N. glutinosa
      was ineffective after dilution to 10-6, after 10 minutes at 70 degrees C and
      after 10 weeks at room temperature. The virus had filamentous and slightly
      flexuous particles with a normal length of about 490-500 nm and 12 nm width.
      According to the symptoms, TIP results and serological comparisons, the compared
      isolates showed no difference and they belong to XN group. In order to estimate
      disease incidence, 773 tubers from Damavand area were tested and compared with
      that in Ardabil area. Disease incidence in Damavand ranged from 1.1-20.9 percent
      and was lower than disease incidence in Ardabil. In 8 genera of collected weeds
      from fields of potato and tomato samples by using test plants and serological
      methods, they didn't show existence of the potato virus x.

PMID- 16637212
TI  - Susceptibility of some Lycopersicon species and varieties to cucumber mosaic
      virus (CMV) and tobacco mosaic virus (TMV).
AB  - Susceptibility of 33 Lycopersicon species and varieties to Tobacco mosaic virus
      (TMV) and Cucumber mosaic virus (CMV) were studied. Plants were mechanically
      inoculated with the C/U1 strain of TMV and U/246 strain of CMV. Virus infection
      was checked by symptomatology, DAS ELISA and back inoculation (biotest). All the
      studied Lycopersicon species and varieties were susceptible to TMV-C/U1. L.
      esculentum Mill. convar. infiniens Lehm. var. flammatum Lehm., L. esculentum
      Mill. convar. fruticosum Lehm. var. speciosum Lehm. and L. esculentum Mill.
      convar. infiniens Lehm. var. validum Bail. showed extreme resistance to CMV
      U/246. The other 30 species and varieties were susceptible to CMV-U/246. New
      compatible and incompatible host-virus relations have been reported. The extreme
      resistant Lycopersicon varieties could be used as resistance sources in tomato
      breeding.

PMID- 16637213
TI  - Study on potato virus M (PVM) occurrence in potato fields in Iran.
AB  - 57 native potato tuber samples collected from different potato growing region of
      Iran, planted on single rows in Karaj College experimental station. Plant samples
      of each single row plus 9.25 Fresh foliage samples collected from fields under
      new introduced cultivars were tested for potato virus (PVM) infection during
      growing season. Also 78 weeds and field crops belonging to Solonacae and
      Leguminosae from or neighboring to potato field were tested. Results indicated
      that PVM was not found on any plant other than potatoes. PVM was detected on 16
      samples of 57 old vars, Virus was not seen in any samples collected from fields
      under new varieties. Results show that PVM is limiting in this crop. PVM
      detecting is difficult using assay hosts. Best test plants were French bean var
      Red kidney, Showing pinpoint necrotic LL, also Datura metel and Nicotiana debneyi
      are useful for virus detection showing chlorotic local lesion. Also
      microprecipition and gel diffusion test can be used for virus detection but Elisa
      was the best method. PVM infected plant showed 11-19.5 percent yield decrease in
      3 cultivars tested.

PMID- 16637214
TI  - Chemical control of ambrosia Artemisiifolia on non-crop areas: are there
      alternatives to glyphosate?
AB  - We compared glyphosate, glufosinate and metsulfuron-methyl to control Ambrosia
      artemisiifolia under non-crop conditions. A laboratory study showed that A.
      artemisiifolia is an easy-to-wet species and that glufosinate and glyphosate are
      quickly absorbed by its leaves (nearly 100% in 24 h). Metsulfuron-methyl
      absorption was slower (about 50% in 24 h) but was strongly promoted by terpenic
      alcohol and esterified rapeseed oil. In the greenhouse, all three herbicides were
      efficacious against A. artemisiifolia, with ED50s of <23, 23 and 0.8 g ha(-1) for
      glufosinate, glyphosate and metsulfuron-methyl, respectively. These results were
      confirmed on a non-crop area for glufosinate and glyphosate, which at half the
      registered dose reached high efficacies at both the 4 to 6-node and flowering
      stages of A. artemisiifolia. By contrast, metsulfuron-methyl showed no efficacy.
      However, after treatment at the 4- to 6-node stage, new emergence of A.
      artemisiifolia led to the presence of vigorous plants that bore numerous flowers
      and produced high levels of pollen. After treatment at the flowering stage,
      flower production by A. artemisiifolia was not significantly affected, but achene
      weight was decreased by 60 to 70% and seed viability was only 8 to 13% for the
      treated plants, as compared to 85% for the control. No significant difference was
      observed between the two herbicides and between the doses. It is concluded that
      glufosinate can be an alternative to glyphosate for the chemical control of A.
      artemisiifolia on non-crop areas. However, with both herbicides, it is difficult
      to attain the two objectives of reducing seed production and pollen production by
      means of only one treatment.

PMID- 16637215
TI  - The chemical control of Shorgum halepense (Johnson grass) in soybean culture in
      the Danube meadow.
AB  - Soybean cultures, especially those from the Danube Meadow, are very strongly
      infested with Johnson grass, which causes big damages, by the reduction of
      production with 40-85%, depending on the infestation degree. Before the synthesis
      of special herbicides for Johnson grass control, this species was controlled by
      practicing deep tilling, repeated operations with the disk, and, after the
      sprouting of soy plants, by mechanical and manual hoeings. In the Danube
      Waterside, the lack of labour force for the manual hoeing is very sharp. For this
      reason, it was generalized the enlarged use of herbicides for annual weed control
      (monocotyledonous and dicotyledonous), including Johnson grass. For the control
      of Johnson grass species, in the conditions of the Danube Meadow, the best
      results were obtained with the herbicides Fusilade Super, Targa Super, Agil and
      Select, and for the control of annual dicotyledonous species, with the herbicide
      Pivot 100LC.

PMID- 16637216
TI  - The chemical weed control of maize culture in the Danube meadow.
AB  - In the world, maize covers about 150 million hectares, following close to rice
      and wheat. (Balteanu 2000) In Romania, maize culture covers an area of more than
      3,500,000 hectares from the overall arable soil, being cultivated in all Romanian
      districts. Chemical weed control took the greatest extension in the world, at the
      same time with the synthesis of Atrazine, in 1956, in the laboratories of J.R.
      Geigy Company, as a super-selective herbicide for the maize culture. This is why
      many researchers from all continents studied weed control of maize culture, using
      Atrazine together with other 50 herbicides synthesized until 2004. In the
      embanked meadow of the Danube, from the 500,000 hectares of arable soil, the
      maize covers the greatest area. For this reasons, the chemical weed control was
      granted a great attention by using different herbicides based on Atrazine,
      Alachlor, Acetochlor, Butilat, Pendimethalin, Dicamba, 2,4-D. At the same time,
      in the experiments from the Danube Meadow, the authors also studied the
      efficiency of some combined herbicides: Butizin, Magnific, Guardian Extra is
      Tazastomp.

PMID- 16637217
TI  - The chemical control of Sorghum halepense species in sunflower culture, in the
      Danube meadow.
AB  - In the latest years, sunflower was cultivated in Romania on an area of 800-900
      thousand hectares. On 100 or 150 thousand hectares we find it cultivated also in
      agricultural farms in the Danube Meadow, because sunflower has favorable
      conditions on these soils, productions exceeding sometimes over 4000 kg/ha, of
      course, in irrigation conditions. In the Danube Meadow, the first experiments on
      Sorghum halepense (Johnson grass) species were performed by Fane Popa and
      colleagues (1986), at the agricultural station of Braila, using the herbicide
      Fusilade. In our experiments, the herbicide fusillade was compared with different
      more recently synthesized herbicides: Super, Pantera, Agil, Select, with the
      specific purpose of identifying the most favorable dose.

PMID- 16637218
TI  - Weed control in sunflower (helianthus annuus L.) with post-emergent herbicides.
AB  - Sunflower is the most important oil crop in Hungary, is the base of the
      production of cooking oil and moreover takes an important part in production of
      margarine too. Extracted sunflower groats as a secondary product origining from
      the mentioned procedure can be used in forage successfully. The amount of
      harvested sunflower reaches the 20-25% of the EU's yield. The sowing area
      approaches 500 thousand hectares. The essential condition of successful crop
      production is the perfect weed control. Sowing areas are infected with
      monocotyledon and dicotyledonous weeds too. Annual dicotyledonous weeds are the
      most troublesome. The worst species is the Ambrosia artemisiifolia L. Many other
      weed species as Abutilon theophrasti MEDIC., Datura stramonium L. and Xanthium
      strumarium L. can cause serious damages. In our model experiments we examined the
      herbicide sensibility of two commercial sunflower cultivars as "Iregi szurke
      csikos", "Marica II" and a sulfonylurea-urea tolerant new hybrid "PR63E82". The
      experiment was set up under greenhouse conditions with the use of four important
      weed and different post-emergent herbicide as Modown 4F (bifenox), Pledge 50 WP
      (flumioxazin) and Granstar 75 DF (tribenuron-methyl). We applied normal and
      double doses too. Sunflower was cultivated to 4-6 leaf stage. Post-emergent
      herbicides were sprayed out when weeds were in 2, 2-4 and 4-6 leaf stage. Weed
      killer and phytotoxic effects of post-emergent herbicides were examined. We
      declared that development of weeds had significally effect on the effectiveness
      of different herbicides.

PMID- 16637219
TI  - Vegetative reproduction and chemical control with post-emergent herbicides of
      field bindweed (Convolvulus arvensis L.).
AB  - It is clearly seen from data that roots of Convolvulus arvensis L. have more and
      less intensive regenerative period during growing season. The more intensive
      period is in autumn, because in that time roots culminate nutrients, carbohydrate
      as starch and sugar. The less intensive regenerative or shoot-growing period is
      in spring, called "late spring bud dormancy". Experiments were conducted to get
      more information and further details about the regenerative capacity of roots
      close to and far from the collar of Convolvulus arvensis L. Root segments closer
      to collar have an intensive regenerative capacity than those ones further to
      collar. By data of Bakke et al. (1939) is well known, roots exhumed from deep
      soil layers are able to create shoots with low intensity. So finally we can
      exclaim that regenerative capacity is decreasing further to collar. Using
      mechanical weed control it is sufficient to till the upper layer of soil, but
      many times. Chemical treatments are most effective in the integrated weed
      control. It is clearly seen that auxin-type herbicide such as 2,4-D, fluroxipir,
      MCPA. dicamba give the best result. They gave 95% weed control effect used them
      separately or in combination with other herbicides. Combination of Banvel 480 S
      (dicamba) and Logran 75 WG (triasulfuron) introduced 95% weed control effect.
      Only one time got absolutely 100% weed control effect, in the case of Glyphosate
      active substance. Caused total plant destruction. Excellent result was given with
      the application of Pledge 50WP (flumioxazin). Herbicides mentioned above are
      absolutely allowed to take an important and significant part in chemical plant
      protection against Convolvulus arvensis L. Other herbicides like Granstar 75DF
      (tribenuron-methyl), Basis 75DF (rimsulfuron + tifensulfuron-methyl) and Huszar
      (jodosulfuron-methyl-sodium + mefenpir-diethyl) are not so effective against
      Convolvulus arvensis L., as compared to the previous ones.

PMID- 16637220
TI  - Susceptibility of some weed species to Pepino mosaic virus (PepMV).
AB  - The aim of our investigations was to study the susceptibility of 22 weed species
      to Pepino mosaic virus (PepMV). Seven plants of each species were mechanically
      inoculated at 4-6 leaf stage with PepMV in a vector free virological glasshouse.
      Inoculated plants were tested on the basis of symptoms, by DAS ELISA serological
      method and back inoculation. Among the 22 weed species, only some Solanum ones
      (S. aethiopicum, S. dulcamara, S. luteum, S. nigrum) were susceptible to PepMV
      infection. All of them--except S. aethiopicum--belong to Hungarian weed flora,
      therefore these weeds--occurring mainly in tomato ecosystems--may play important
      role in the epidemiology of PepMV. Other 18 weed species seemed to be resistant
      to PepMV, and on the basis of back inoculation not even latent infection has been
      observed.

PMID- 16637221
TI  - Growth and yield of groundnut (Arachis hypogaea L.) as influenced by weed
      management practices and Rhizobium inoculation.
AB  - Groundnut (Arachis hypogaea L.) productivity in India is low, because of many
      problems beset in its cultivation. One of the serious problems are weeds.
      Groundnut yield losses due to weeds have been estimated as high as 24 to 70
      percent. This has created a scope for using herbicides in groundnut crop. A field
      investigation was carried out during kharif (rainy) season of 2001-2002 on a
      sandy loam soil at College Agronomy Farm, B.A. College of Agriculture, Gujarat
      Agricultural University, Anand, India to study the effect of weed management
      practices and Rhizobium inoculation on growth and yield of groundnut (Arachis
      hypogaea L.). Ten weed control treatments, comprising four treatments of sole
      application of fluchloralin, pendimethalin, butachlor and metolachlor,
      respectively each applied at 1.0 kg ha(-1); four treatments comprising of an
      application of the same herbicides at the same levels coupled with one hand
      weeding at 30 DAS; one weed-free treatment (hand weedings at 15, 30, 45 DAS); and
      one unweeded control. All 10 treatmets were combined with and without Rhizobium
      inoculation (i.e. a total of 20 treatment combinations) under a factorial
      randomized complete block design (FRBD) with four replications. Minimum weed dry
      matter accumulation (70 kg/ha) with higher weed control efficiency (90.70%) was
      recorded under an integrated method i.e. pendimethalin at 1.0 kg ha(-1) + hand
      weeding at 30 DAS, which also resulted in maximum pod yield (1773.50 kg ha(-1)).
      This treatment was comparable to fluchloralin applied at 1.0 kg ha(-1) combined
      with hand- weeding at 30 DAS. Weedy conditions in the unweeded control treatment
      reduced pod yield by 29.90-35.95% as compared to integrated method. Significantly
      higher pod yield was obtained with Rhizobium inoculation than the mean value of
      all treatments without inoculation. For most agronomical parameters examined,
      Rhizobium inoculation and weed control treatments were independent in their
      effect.

PMID- 16637222
TI  - Resistance to metamitron in Chenopodium album from sugar beet. a tale of the
      (un)expected?
AB  - Metamitron is a key herbicide in modern low rate weed control programs in sugar
      beet. Fat hen (Chenopodium album, CHEAL) is a common, highly competitive, weed in
      sugar beet and one of the targets of metamitron. Recently, unsatisfactory control
      of fat hen has been reported in several sugar beet fields situated in various
      regions in Belgium. Weather conditions as well as the mere fact of using low rate
      systems have been blamed for these poor performances. To address the question "Is
      the recently recorded poor control of C. album due to decreased sensitivity to
      metamitron", greenhouse bioassays were carried out. A first experiment was
      conducted applying metamitron (0, 350, 700 and 1,400 g ai/ha) postemergence to
      three "suspected" C. album populations originating from sugar beet fields with
      unsatisfactory control by standard metamitron based treatment schemes ('Ligne',
      'Outgaarden' and 'Boutersem I' respectively) and to one sensitive population
      originating from an untreated garden site ('Gent'). In a second experiment seven
      population, five "suspected" fat hen populations from sugar beet fields
      ('Boutersem I', 'Boutersem II', 'Postel', 'Vissenaken' and 'Kortessem'
      respectively), one sensitive reference population 'Herbiseed' and one atrazine
      resistant reference population 'ME.85.01', were submitted to metamitron (0, 1, 2
      and 4 mg ai/kg air-dry soil) and atrazine (1.5 mg ai/kg air-dry soil) preplant
      incorporated. All "suspected" C. album populations displayed a significantly
      lower sensitivity to metamitron compared to the sensitive populations ('Gent' and
      'Herbiseed') that never had been exposed to this herbicide. As target site cross
      resistance of atrazine-resistant C. album, selected by atrazine in maize, to
      metamitron has been known for a long time, cross-resistance of C. album
      populations in sugar beet grown on fields with "maize - atrazine" containing
      rotations might be expected to appear. The outcome of the experiment with
      atrazine preplant incorporated was the confirmation of resistance in all
      "suspected" populations ('Boutersem I', 'Boutersem II', 'Postel', 'Vissenaken'
      and 'Kortessem'). However, some "suspected" populations came from fields with no
      background of cropping with maize and use of atrazine. So, the question remains
      whether these triazine-resistant C. album had been imported, e.g. with slurry, or
      the rather unexpected possibility that metamitron itself did select for
      metamitron-resistant biotypes bearing cross-resistance to atrazine, had become
      reality.

PMID- 16637223
TI  - Glyphosate resistance in a Chilean Lolium multiflorum.
AB  - Lolium multiflorum (Italian ryegrass) has recently demonstrated itself to be
      poorly controlled with glyphosate in cereal crops of South Chile. The
      concentration of glyphosate necessary to reduce shoot length by 50% (ED50) in
      seedlings, after eight days of root contact was 7.3-fold in the resistant Vil-1
      than in the susceptible (S) biotype. The obtained spray retention values were
      higher on S than the resistant (Vil-1) biotype. Contact angles measured on the
      adaxial surface of S and Vil-1 were similar. However, on the abaxial surface
      contact angles were of 63 degrees on Vil-1 as compared to 42 degrees on S. A
      greater glyphosate uptake was observed through the abaxial surface of S.
      Regarding translocation, glyphosate accumulated mainly in the tip of the treated
      leaf of Vil-1, 24 h after treatment. It was afterwards also well distributed to
      the rest of the leaves and roots, as in the susceptible biotype. Nevertheless,
      14C-glyphosate remained higher in the foliar apex of Vil-1. Hence, resistance to
      glyphosate by the Vil-1 Lolium multflorum biotype seems to involve a lower uptake
      through the abaxial leaf surface and a different migration pattern.

PMID- 16637224
TI  - Comparative therapeutic effects of alendronate and alfacalcidol on cancellous and
      cortical bone mass and mechanical properties in ovariectomized osteopenic rats.
AB  - The purpose of the present study was to compare the therapeutic effects of
      alendronate and alfacalcidol on the cancellous and cortical bone mass and
      mechanical properties in ovariectomized osteopenic rats in a head-to-head
      fashion. Twenty-five female Sprague-Dawley rats, 7 mo of age, were randomly
      divided by the stratified weight method into four groups: the sham-operated
      control (Sham) group and three ovariectomized groups treated with vehicle,
      alendronate (2.5 mg/kg, p.o., daily), or alfacalcidol (0.5 microg/kg, p.o.,
      daily). Treatment was started 6 wk after the surgery and continued for 6 wk. At
      the end of the experiment, urinary deoxypyridinoline (DPD) and serum osteocalcin
      (OC) levels were evaluated, and cancellous and cortical bone histomorphometric
      analyses were performed for the proximal tibial metaphysis and tibial diaphysis,
      respectively. Alendronate prevented the elevation of the urinary DPD level
      induced by ovariectomy (OVX), and markedly decreased the serum OC level to below
      the value observed in the Sham group, while alfacalcidol prevented the elevation
      of the urinary DPD and serum OC levels induced by OVX. Alendronate increased the
      cancellous bone volume/total tissue volume (BV/TV) relative to the values
      observed in the OVX-Vehicle group by preventing the increases in the eroded
      surface/bone surface (ES/BS), osteoclast surface (OcS)/BS, and bone formation
      rate (BFR)/BS induced by OVX. However, it decreased the mineral apposition rate
      (MAR) in the ovariectomized osteopenic rats to below the value observed in the
      Sham group. It also prevented the increase in the marrow area (Ma Ar) caused by
      OVX. Alfacalcidol increased the BV/TV relative to the values observed in the OVX
      Vehicle group by decreasing the ES/BS and OcS/BS, but maintaining the BFR/BS. The
      effect of alfacalcidol on the BV/TV was more pronounced than that of alendronate,
      despite the less pronounced suppression of OcS/BS by this drug in the
      ovariectomized osteopenic rats. In addition, this drug increased the cortical
      area (Ct Ar) and prevented the increase in the Ma Ar in the ovariectomized
      osteopenic rats by decreasing the endocortical ES/BS, and even increasing the
      endocortical BFR/BS. Furthermore, it also prevented the reduction in the maximum
      load of the femoral distal metaphysis in the ovariectomized osteopenic rats.
      Thus, the present study clearly showed that alendronate and alfacalcidol had
      differential therapeutic effects on the cancellous and cortical bone mass and
      mechanical properties in ovariectomized osteopenic rats.

PMID- 16637225
TI  - Comparative oral toxicity of coenzyme Q10 and its (2Z)-isomer in rats: single and
      four-week repeated dose toxicity studies.
AB  - It has been reported that coenzyme Q10 (CoQ10) functions as an electron transfer
      carrier in mitochondria, and can produce an improvement in heart diseases such as
      congestive heart failure. Its (2Z)-isomer contains a cis-double bond at the 2
      position of the decaprenyl side chain. As the original organic industrial
      synthesis of CoQ10 resulted in a product that contained a small amount of this
      isomer, the efficacy and safety of CoQ10 was determined using CoQ10 containing
      this isomer; however, no toxicity data have been reported for the (2Z)-isomer
      itself. Thus, we conducted single (2,000 mg/kg) and 4-wk repeated (1,000 mg/kg)
      oral dose toxicity studies in rats to compare the toxicological profiles of CoQ10
      and its (2Z)-isomer. The two compounds displayed similar toxicological profiles,
      and it was concluded that neither CoQ10 nor its (2Z)-isomer produce toxic effects
      in rats in single or repeated doses.

PMID- 16637226
TI  - Comparative effects of risedronate and calcitriol on cancellous bone in rats with
      glucocorticoid-induced osteopenia.
AB  - OBJECTIVES: To compared the effects of risedronate (Ris) and calcitriol (Cal) on
      cancellous bone in rats with glucocorticoid (GC)-induced osteopenia. MATERIALS
      AND METHODS: Thirty female Sprague-Dawley rats, 4 mo of age, were randomly
      divided by the stratified weight method into three groups of 10 rats each
      according to the following treatment schedule: 8-wk GC administration with 4-wk
      vehicle (control), Ris, and Cal as therapeutic treatment initiated after 4-wk GC
      administration. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.),
      Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg. p.o.) were administered 3 times
      a week. At the end of the 8-wk treatment period, two-dimensional (2D) bone
      histomorphometric analysis was performed for cancellous bone of the proximal
      tibial metaphysis, 3D micro-computed tomographic analysis was performed for the
      distal femoral metaphysis, and the mechanical strength of the distal femoral
      metaphysis was evaluated by a compression test. RESULTS: Ris and Cal treatment
      increased both 2D and 3D cancellous bone mass. However, Ris treatment exhibited
      more pronounced effects on 2D and 3D cancellous bone mass than Cal treatment, and
      the effects of both Ris and Cal treatment were greater on 3D cancellous bone mass
      than on 2D cancellous bone mass. The response of 2D and 3D cancellous bone mass
      to Ris treatment was characterized by its effect on trabecular number and
      thickness, which was associated with markedly suppressed bone resorption and bone
      formation in terms of suppressed bone turnover. On the other hand, the response
      of 2D cancellous bone mass to Cal treatment was attributed to the effect of Cal
      on 2D trabecular thickness, and the response of 3D cancellous bone mass to Cal
      treatment might be characterized by the effect of Cal on 3D trabecular number and
      thickness, with a more marked effect of trabecular thickness. These effects were
      primarily due to mildly suppressed bone resorption and maintained or even
      increased bone formation. Despite the differential effect of Ris and Cal
      treatment on the cancellous bone structure and bone metabolism, both treatment
      increased the maximum load and braking energy of the distal femoral metaphysis to
      a similar extent, suggesting different mechanisms for improving bone strength.
      CONCLUSIONS: This study showed the differential effects of Ris and Cal on
      cancellous bone in rats with GC-induced osteopenia.

PMID- 16637227
TI  - Ascorbic acid deficiency stimulates hepatic expression of inflammatory chemokine,
      cytokine-induced neutrophil chemoattractant-1, in scurvy-prone ODS rats.
AB  - ODS rat has a hereditary defect in ascorbic acid biosynthesis and is a useful
      animal model for elucidating the physiological role of ascorbic acid. We
      previously demonstrated by using ODS rats that ascorbic acid deficiency changes
      the hepatic gene expression of acute phase proteins, as seen in acute
      inflammation. In this study, we investigated the effects of ascorbic acid
      deficiency on the production of inflammatory chemokine, cytokine-induced
      neutrophil chemoattractant-1 (CINC-1), in ODS rats. Male ODS rats (6 wk of age)
      were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without
      ascorbic acid for 14 d. Obvious symptoms of scurvy were not observed in the
      ascorbic acid-deficient rats. Ascorbic acid deficiency significantly elevated the
      serum concentration of CINC-1 on d 14. The liver and spleen CINC-1 concentrations
      in the ascorbic acid-deficient rats were significantly elevated to 600% and 180%
      of the respective values in the control rats. However, the lung concentration of
      CINC-1 was not affected by ascorbic acid deficiency. Ascorbic acid deficiency
      significantly elevated the hepatic mRNA level of CINC-1 (to 480% of the value in
      the control rats), but not the lung mRNA level. These results demonstrate that
      ascorbic acid deficiency elevates the serum, liver and spleen concentrations of
      CINC-1 as seen in acute inflammation, and suggest that ascorbic acid deficiency
      stimulate the hepatic CINC-1 gene expression.

PMID- 16637228
TI  - Effects of different grape formulations on antioxidative capacity, lipid
      peroxidation and oxidative DNA damage in aged rats.
AB  - In this study, the freeze-dried powders from whole grapes, pomace and juice of
      Campbell Early (Vitis labruscana Bailey) were prepared to determine the amount of
      total flavonoids, vitamins A, C, and E, and dietary fiber. Effects of whole
      grape, pomace, or juice intakes on their antioxidative capacity and DNA damage
      were investigated in Sprague-Dawley male rats. A total of 120 rats at 13 mo old
      and weighing 549 +/- 4 g were blocked into 8 groups according to body weight and
      raised for 3, 5, or 7 mo with diets containing 2% (w/w) dry powder of three
      different parts of grapes and 0.02% (w/w) CdCl2. The contents of flavonoids,
      antioxidant vitamins A and E, and dietary fiber in freeze-dried powder were the
      highest in grape pomace, but the vitamin C contents were similar among the three
      powders. In all the 16, 18, and 20-mo-old animals, plasma and liver
      thiobarbituric acid reactive substances levels of grape-ingesting groups were
      lower than those of the controls and that of the grape pomace group was the
      lowest among the groups. Cd administration increased plasma and liver
      thiobarbituric acid reactive substances levels remarkably; however, Cd+grape
      groups were lower than the Cd-control group. Red blood cell superoxide dismutase
      activity of 18- and 20-mo-old rats was higher than that of 16-mo-olds, showing an
      age-related increase; however, red blood cell catalase and glutathione peroxidase
      activities decreased with age. Grape diets promoted superoxide dismutase,
      catalase, glutathione peroxidase activities, and the grape pomace increased the
      activities most significantly among three different parts of the grape. Cd
      decreased superoxide dismutase, catalase, glutathione peroxidase activities;
      however Cd+grape groups showed similar activities to the non-Cd control group.
      Liver superoxide dismutase activity was decreased with age but catalase activity
      of 18-mo-old rats was higher than those of 16- and 20-mo-old groups, and
      glutathione peroxidase activities of 16- and 18-mo-old groups were similar but
      that of 20-mo-old groups decreased markedly. Grape intake increased these three
      antioxidative enzyme activities while Cd administration decreased catalase and
      glutathione peroxidase activities except superoxide dismutase activity. The
      concentration in the kidney of 8-hydroxy-2'-deoxyguanosine in the 18- and 20-mo
      old rats was higher than that in the 16-mo-old groups, and grape intake showed a
      protecting effect on DNA from age-related or Cd-induced oxidative damage. In
      conclusion, grape intakes, especially grape pomace with the highest content of
      flavonoids, beta-carotene, tocopherols and dietary fiber among the three parts,
      showed the prominent antioxidative capacity of inhibiting age-related or Cd
      induced increase of lipid peroxidation and DNA damage effectively, promoting
      liver and red blood cell antioxidant enzyme activities.

PMID- 16637229
TI  - Basal lipolysis in epididymal fat cells from streptozotocin-induced diabetic
      rats.
AB  - The level of free fatty acid (FFA) in plasma is increased by diabetes. The
      increase in plasma FFA levels accompanied the stimulation of basal lipolysis
      (i.e. lipolysis in the absence of lipolytic agents) in fat cells. Injection of
      streptozotocin with rats resulted in a significant increase in basal FFA
      production (5.5 fold) in fat cells. However, basal glycerol production in fat
      cells was increased only 1.5 fold by streptozotocin-induced diabetes, implying
      that FFA re-esterification in fat cells was decreased by streptozotocin-induced
      diabetes. The FFA re-esterification in fat cells was also decreased by 1 d of
      fasting. Although basal lipolysis was increased by streptozotocin-induced
      diabetes or 1-d fasting, neutral triacylglycerol lipase activity and the
      immunoreactive HSL protein content in fat cells from streptozotocin-induced
      diabetic rats or 1-d fasting rats were not significantly changed. Although beta
      blockers inhibited lipolysis induced by norepinephrine at a concentration of 10(
      4) M, it failed to inhibit the basal lipolysis and FFA re-esterification in fat
      cells from streptozotocin-induced diabetic rats. Nor did insulin or H-89, another
      antilipolytic agent, affect basal lipolysis or FFA re-esterification in fat cells
      from streptozotocin-induced diabetic rats. These results indicate that basal FFA
      production may be induced by a decrease of re-esterification of FFA in diabetic
      rats and is not affected by antilipolytic agents such as insulin, beta-blockers
      or H-89.

PMID- 16637230
TI  - Difference in plasma metabolite concentration after ingestion of lemon flavonoids
      and their aglycones in humans.
AB  - The concentrations of metabolites in human plasma after ingestion of flavanone
      glycosides (FG) and their aglycones (FA) in lemon were examined. FG consisting
      abundantly of eriocitrin were prepared from lemon peel and FA consisting
      abundantly of eriodictyol were prepared from FG by treatment with beta
      glucosidase. Eriodictyol, homoeriodictyol, and hesperetin in plasma up to 4 h
      after ingestion of FG with water or FA with water by subjects were not detected
      in plasma of non-enzyme treatment but in plasma after treatment with beta
      glucronidase and sulfatase. Metabolites in plasma after ingestion of FG and FA in
      humans were shown to exist as the glucuro- and/or sulfo-conjugates of
      eriodictyol, homoeriodictyol, and hesperetin. After ingestion of FA, the
      concentration of metabolites in plasma exhibited a high maximum peak at 1 h. The
      AUC (area under the blood concentration time curve) level of metabolites of FA
      was higher than that of FG. FA were suggested to be absorbed faster and in higher
      amounts than FG. The AUC of metabolites in subject plasma after ingestion of FG
      with flavonoid-depleted lemon juice was shown to change to a low level in
      comparison with that of FG with water. The maximum concentration peak of
      metabolites in plasma was faster at 0.5 h than FA with water but the AUC level
      was similar to FA with water, when subjects ingested FA with vodka (40%,
      ethanol). The absorption hour of FG and FA was shown to be affected by the co
      existing solution.

PMID- 16637231
TI  - Hyperhomocysteinemia can be ameliorated by dimethylsulfoniopropionate in place of
      folic acid in mice.
AB  - Acute homocysteinemia mice were prepared by forcibly oral administration of
      homocysteine (4 mM, 2 mL). The amounts of plasma homocysteine were estimated by a
      fluorescence method with HPLC. Folic acid (0.6 mM, 2 mL), DMSP, or betaine (20
      mM, 2 mL each) was intraperitoneally administrated into the mice suffered from
      the acute homocysteinemia on the 20th, 40th or 60th min after the oral
      supplementation of homocysteine, then amounts of plasma homocysteine were
      determined by the HPLC method 40 min after each addition, respectively. The
      results indicated that the intraperitoneal addition of folic acid or DMSP in this
      order of the 40th, 60th and 20th min after the oral supplementation of
      homocysteine significantly reduce the quantities of plasma homocysteine, but
      betaine exerted the fairly lesser effects. The amounts of homocysteine without
      any additive linearly and rapidly appeared to increase up to 60 min, at which
      those were about 8-12 fold the normal levels of homocysteine, and thereafter
      decreased in these experiments. Accordingly, folic acid which is known to
      effectively improve homocysteinemia was proven to be completely replaced by DMSP
      under the experimental conditions.

PMID- 16637232
TI  - Influence of temperature on short-chain fatty acid production by pig cecal
      bacteria in vitro.
AB  - We studied the effect of incubation temperature on the production of shortchain
      fatty acids (SCFA) by pig cecal bacteria in vitro in order to assess short-term
      influences of body temperature on bacterial metabolism in the large intestine. We
      employed a 200 mL scale continuous culture system using cecal bacteria from
      commercially slaughtered pigs as innoculum. The culture was maintained at 30, 37,
      40 or 42 degrees C and continuously diluted by continuous feeding of bicarbonate
      buffer (pH 7.4) added with lactose (10 g/L) and by simultaneous continuous efflux
      both at 4.17 mL/h. We monitored SCFA concentration of the culture for 12 h, which
      represents their production rate. Concentrations of SCFA increased during the
      first several hours and plateaued at around 11 h of incubation. Incubation
      temperature significantly affected mean concentrations from 1 to 12 h of acetic
      (40 degrees C>42 degrees C= 37 degrees C>30 degrees C), propionic (40 degrees
      C>42 degrees C=30 degrees C), n-butyric (42 degrees C>37 degrees C>30 degrees C,
      40 degrees C>30 degrees C) and n-valeric (42 degrees C=40 degrees C>37 degrees
      C>30 degrees C) acids, and total SCFA (40 degrees C>42 degrees C= 37 degrees C>
      30 degrees C) (p<0.05). These results indicate that both hyperthermia and
      hypothermia depress the microbial breakdown of carbohydrates.

PMID- 16637233
TI  - Ameliorating effect of dimethylsulfoniopropionate on the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-induced Parkinson's disease of mice.
AB  - The effect of dimethylsulfoniopropionate (DMSP) on the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced Parkinson's disease (PD) of mice was examined for 5 d.
      The distilled water (the control group) and the DMSP solution at 5 x 10(-4) M
      (the DMSP group) were supplemented ad libitum to six mice each in two groups for
      2 wk. An appropriate amount of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) solution (20 mg/kg body wt) was then intraperitoneally injected into all
      the test mice once a day initially for 3 d, which definitely made the control
      mice similar to the PD-model mice. The moving ability (running power) of the mice
      in both groups was measured using an automatic Wheel Running Instrument. The
      immobility duration of the upside-down mice in both groups was estimated by a
      newly developed polygraph (RMP-6008M, Nihon Koden Co., Ltd., Japan). The results
      indicated that the mice in the DMSP group showed a stronger moving ability and a
      shorter immobility duration compared to the mice in the control group during the
      experimental period. Furthermore, the amounts of catecholamines (dopamine and
      norepinephrine) in the brains except for the cerebellums of all the test mice
      were estimated 2 d after the last MPTP injection, which demonstrated that the
      brains of the mice in the DMSP group accumulate larger amounts of catecholamines,
      especially dopamine, than them in the control group. Accordingly, the
      administration of low concentrations of DMSP proved to prevent and/or ameliorate
      the decreased mobility and the typical immobility (Akinesia) of the MPTP-induced
      PD-model mice probably due to increased amounts of dopamine in the brains of the
      DMSP group mice.

PMID- 16637234
TI  - Gly395Arg polymorphism of PPARalpha gene was not detected in Japanese population
      of 729 individuals.
AB  - Peroxisome proliferator-activated receptor a (PPARalpha) is a member of the
      nuclear receptor superfamily and participates in the regulation of key proteins
      involved in lipid metabolism, fatty acid oxidation, homeostasis, and
      inflammation. Several polymorphisms of the human PPARalpha gene, such as
      Leu162Val polymorphism and Val227Ala polymorphism, have been described in
      different races. Recently, another PPARalpha polymorphism Gly395Arg polymorphism
      has been reported in Caucasian and African subjects. Using the Invader assay, we
      searched for this polymorphism in 729 Japanese adults randomly selected in a
      rural population. Although the synthesized oligonucleotides of each polymorphism
      could be distinguished clearly, all 729 individuals had the Gly (G) allele and
      none had the Arg (C) allele. These data suggest that there is racial variability
      in the frequencies of PPARalpha gene polymorphisms.

PMID- 16637235
TI  - Measurement of dietary choline-phospholipid content by a novel phospholipase D
      triiodide method.
AB  - We developed a novel method that conveniently measures dietary choline
      phospholipid content. Crude lipids extracted from dietary samples were reacted
      with phospholipase D from Streptomyces chromofuscus. The choline liberated from
      this reaction was then reacted with potassium triiodide, yielding choline
      periodide, which could be measured spectrophotometrically at 365 nm. This method
      proved to be more convenient than conventional assays, such as thin layer
      chromatography and high performance liquid chromatography. Our novel method is
      suitable for measuring many samples in single experiments.

PMID- 16637236
TI  - Invasive pneumococcal disease in Australia, 2004.
AB  - There were 2,375 cases of invasive pneumococcal disease (IPD) notified to the
      National Notifiable Diseases Surveillance System in Australia in 2004; a
      notification rate of 11.8 cases per 100,000 population. The rate varied between
      states and territories and by geographical region with the highest rates in the
      Northern Territory. Invasive pneumococcal disease was reported most frequently in
      children aged less than 5 years (55.4 cases per 100,000 population). Enhanced
      surveillance for IPD was carried out in all states and territories, in 2004,
      providing additional data on 2,023 (85%) cases. The overall rate of IPD in
      Indigenous Australians was 3.2 times the rate in non-Indigenous Australians.
      There were 154 deaths attributed to IPD resulting in an overall case fatality
      rate of 7.6 per cent. Rates of IPD in the Indigenous and non-Indigenous under 2
      year-old population were similar in 2004 (91.5 and 93.6 cases per 100,000
      population, respectively) following a targeted introduction of the 7-valent
      pneumococcal conjugate vaccine (7vPCV) in mid-2001 for Indigenous infants and
      children. Serotypes of isolates were identified from 80 per cent of all notified
      cases, with 72 per cent of isolates belonging to serotypes represented in the
      7vPCV and 91 per cent in the 23-valent polysaccharide pneumococcal vaccine
      (23vPPV). Comparison of serotypes in the 7vPCV target population showed that the
      rate of IPD due to 7vPCV serotypes decreased by 74 per cent between 2001-02 and
      2003-04. Of 216 isolates with reduced penicillin susceptibility, 83 per cent
      belonged to pneumococcal serotypes in the 7vPCV and 95 per cent in the 23vPPV.

PMID- 16637237
TI  - Tuberculosis notifications in Australia, 2004.
AB  - The National Notifiable Disease Surveillance System received 1,076 tuberculosis
      (TB) notifications in 2004, of which 1,043 were new cases and 33 were relapses.
      The incidence of TB in Australia has remained at a stable rate since 1985 and was
      5.4 cases per 100,000 population in 2004. The high-incidence groups remain people
      born overseas and Indigenous Australians at 21.7 and 8.1 cases per 100,000
      population, respectively. By contrast, the incidence of TB in the non-Indigenous
      Australian-born population was 1.0 cases per 100,000 population. Comparison of
      the 2004 TB notification data against the performance indicators set by National
      Tuberculosis Advisory Committee highlights that enhanced TB control measures
      should be considered among these high-risk groups.

PMID- 16637238
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2004: a report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new cases of disease caused by Mycobacterium tuberculosis
      complex in the year 2004. A total of 787 cases were identified by bacteriology,
      representing an annual reporting rate of 3.9 cases per 100,000 population. Almost
      all isolates were identified as M. tuberculosis (n = 785), the remaining isolates
      being one each of Mycobacterium africanum and Mycobacterium canettii. Seven
      children under 10 years of age (female n = 5, male n = 2) had bacteriologically
      confirmed tuberculosis (gastric aspirate n = 4, lymph node n = 1, pleural n = 1,
      thigh wound n = 1). Results of in vitro drug susceptibility testing were
      available for all 787 isolates for isoniazid (H), rifampicin (R), ethambutol (E),
      and pyrazinamide (Z). A total of 71 (9.0%) isolates of M. tuberculosis were
      resistant to at least one of these anti-tuberculosis agents. Resistance to at
      least both H and R (defined as multidrug resistance) was detected in 12 (1.5%)
      isolates; 10 were from the respiratory tract (sputum n = 7, bronchoscopy n = 3).
      The country of birth was known for 68/71 (95.8%) cases with a drug resistant
      strain; eight were Australian, 60 were overseas born, and three were unknown. Of
      the 60 migrants with drug resistant disease, 37 (61.7%) were from three
      countries; Viet Nam (n = 20), China (n = 9) and India (n = 8).

PMID- 16637239
TI  - The BCG vaccine: information and recommendations for use in Australia.
AB  - The Bacille Calmette-Guerin (BCG) vaccine since its first use in 1921 has been
      the subject of much controversy as to its effectiveness and applicability. BCG
      vaccination is still considered an important strategy in the National
      Tuberculosis Programs of countries with a high burden of tuberculosis (TB)
      because of its benefit to infants but its effect on the control of TB has been
      limited. By contrast, in countries with a low prevalence of TB, significant
      policy differences exist both within and between countries. BCG vaccination does
      not prevent transmission of infection to the individual. In immune-competent
      neonates and infants it is accepted that BCG reduces the likelihood of TB
      infection progressing to disease or if disease occurs, substantially lessens the
      chance of a severe outcome. The benefit in older agegroups is less clear. In the
      Australian health worker, the BCG strategy is no longer recommended as the
      primary means of health care worker (HCW) protection. The preferred strategy is
      appropriate infection control measures, staff education and a tuberculin skin
      testing program that identifies and treats the at-risk infected HCW. The
      emergence of multi-drug resistant strains has however renewed interest in BCG in
      the HCW. This document provides recommendations for use of the BCG vaccine in the
      Australian community based on the best available evidence and consensus opinion.
      State and Territory TB Control Units should be consulted with regard to their BCG
      vaccination guidelines.

PMID- 16637240
TI  - Guidelines for Australian mycobacteriology laboratories.
AB  - Guidelines for Australian laboratories performing tuberculosis (TB) microscopy
      and culture have been developed through extensive consultation with expert
      groups. The aims of these guidelines are: 1. To provide consensus recommendations
      on the infrastructure, equipment and work practices required by mycobacteriology
      laboratories; 2. To inform laboratory administrations and governments of the
      necessary level of investment required to maintain modern mycobacteriology
      facilities; and 3. To provide informal measures for reviewers inspecting
      mycobacteriology facilities. These guidelines include safety recommendations
      based largely on the Australian/New Zealand Standard 2243.3 Safety in
      laboratories--Microbiological aspects and containment facilities. However, these
      standards have been rationalised and PC2 facilities with additional processes and
      precautions in place are recommended for the majority of TB investigations.
      Guidelines are also provided on staff training, education, health screening and
      vaccination. Certain procedures and work practices are recommended for
      mycobacteriology laboratories to guarantee safety, high-quality results, and
      prompt turnaround times. These guidelines will be reviewed each 1-2 years and
      feedback from expert groups and individuals is welcomed.

PMID- 16637241
TI  - Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western
      Pacific Region, 2004.
AB  - The World Health Organization Western Pacific Region Gonococcal Antimicrobial
      Surveillance Programme (WHO WPR GASP) examined approximately 10,000 isolates of
      Neisseria gonorrhoeae from 15 countries for resistance to antibiotics in 2004.
      Treatment options for gonorrhoea in the Region are limited by persisting high
      rates of resistance to penicillins and quinolones. There were infrequent
      instances of spectinomycin resistance and the presence of gonococci with
      decreased susceptibility to third generation cephalosporins was again noted in
      several centres.

PMID- 16637242
TI  - National Rotavirus Surveillance Program annual report, 2004-05.
AB  - The National Rotavirus Reference Centre together with collaborating laboratories
      Australia-wide has conducted rotavirus surveillance since June 1999. This report
      describes the serotypes of rotavirus strains responsible for the hospitalisation
      of children with acute gastroenteritis during the period 1 July 2004 to 30 June
      2005. Six hundred and twelve faecal samples from across Australia were examined
      using monoclonal antibody immunoassays, reverse transcription-polymerase chain
      reaction and polyacrylamide gel analysis. Serotype G1 was the dominant serotype
      nationally, representing 48.3 per cent of all strains, followed by serotype G3
      (36.7%) and serotype G9 (6.9%). As in previous years, there was substantial
      geographic variation in the prevalence of rotavirus serotypes.

PMID- 16637243
TI  - Influenza surveillance in Victoria, 2005.
AB  - Influenza activity remained within normal seasonal activity with a well-defined
      peak at week 29 (beginning 18 July) during the Victorian influenza season from
      May to September 2005. Surveillance was based on sentinel general practice
      influenza-like illness (ILI) notifications with laboratory confirmation, medical
      locum service ILI notifications and laboratory notification of influenza
      detections. One thousand and eighty-seven consultations for ILI were reported
      from 38 general practices, while medical practitioners from the locum service
      reported 317 consultations for ILI. The average weekly rate of ILI from sentinel
      surveillance was 7.3 per 1,000 consultations. Similar numbers of influenza A
      subtypes H1N1 and H3N2 were detected; 45 per cent of which were
      A/California/7/2004-like (H3), 44 per cent were A/New Caledonia/20/99-like (H1)
      and 11 per cent were A/Wellington/1/2004 (H3). Of the influenza B samples, 67 per
      cent were B/Hong Kong/330/2001-like and 33 per cent were B/Shanghai/361/2002
      like. The influenza vaccine for 2005 contained: A/New Caledonia/20/99(H1N1)-like
      virus, A/Wellington/ 1/2004(H3N2)-like virus, and B/Shanghai/361/2002-like virus.
      Although the predominant H3 and B circulating strains were not included in the
      vaccine, there was reasonable serological cross protection between vaccine and
      circulating strains.

PMID- 16637244
TI  - Creutzfeldt-Jakob disease: Australian surveillance update to December 2005.
AB  - Australia-wide prospective surveillance of human transmissible spongiform
      encephalopathies (TSEs) has been conducted by the Australian National Creutzfeldt
      Jakob Disease Registry (ANCJDR) since October 1993. In addition, the Registry
      retrospectively ascertained TSE cases within Australia from 1970. Referrals of
      all suspect cases of human prion diseases or TSEs are investigated by the ANCJDR
      and include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker
      syndrome, fatal familial insomnia and variant CJD. This semi-annual progressive
      update presents epidemiological findings of the ANCJDR based on Australian data
      obtained for the period 1970 to 31 December 2005.

PMID- 16637245
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, 1 October to 31 December 2005.

PMID- 16637246
TI  - A report from the Communicable Diseases Network Australia: 1 October to 31
      December 2005.

PMID- 16637247
TI  - Surveillance systems reported in CDI, 2006.

PMID- 16637248
TI  - Communicable diseases surveillance: highlights for 4th quarter, 2005.

PMID- 16637249
TI  - Successful thermal therapy for end-stage peripheral artery disease.

PMID- 16637250
TI  - [Estimation of myocardial ischemia by diastolic strain analysis in exercise
      stress echocardiography: comparison with exercise thallium-201 single photon
      emission computed tomography].
AB  - OBJECTIVES: The feasibility of detecting persistent regional left ventricular
      abnormal relaxation due to myocardial ischemia using strain echocardiography
      several minutes after exercise was investigated. METHODS: Consecutive 27 patients
      (mean age 65 +/- 9 years, 21 males, 6 females) with suspected coronary artery
      disease were enrolled. Strain echocardiographic images were acquired at the mid
      segments of the left ventricular wall before and 5 min after exercise in the
      apical long-axis, two-chamber and four-chamber views. Strain curves were obtained
      at each segment, and peak values of strain at the closure of aortic valve (A) and
      at one third of diastolic duration (B) were measured. Strain diastolic index
      (SDI) was calculated as (A - B)/A X 100%. The ratio of SDI before exercise to
      that after exercise was defined as the SDI ratio and compared with exercise
      thallium-201 single photon emission computed tomography (SPECT) as the reference
      standard to detect myocardial ischemia. RESULTS: A total of 162 segments were
      evaluated. Based on the results of exercise SPECT, 119 segments were classified
      as non-ischemic segments, and 43 as ischemic segments. Ischemic segments showed
      significant decreases in SDI before and after exercise, whereas non-ischemic
      segments showed no significant differences in SDI before and after exercise. SDI
      ratio was significantly decreased in ischemic segments, but not in non-ischemic
      segments. SDI ratio with a cut off value of 0.51 had a sensitivity of 91% and a
      specificity of 89% to detect myocardial ischemia in the receiver-operating
      characteristics. Conclusions. Strain echocardiography can provide quantitative
      assessment of myocardial ischemia by detecting post-ischemic regional left
      ventricular delayed relaxation even 5 min after exercise.

PMID- 16637251
TI  - [Prognostic value of C-reactive protein and troponin T level in patients with
      unstable angina pectoris].
AB  - OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately
      predicted by the combination of C-reactive protein (CRP), which is a known
      inflammation marker, and troponin T (TnT), which is used for risk assessment for
      the prognosis of acute coronary syndrome. The present study investigated the
      correlations between pathophysiology and prognosis of severe unstable angina
      pectoris and CRP and TnT levels. METHODS: The correlation between CRP at
      admission and the prognosis was studied in 367 patients with severe unstable
      angina pectoris (Braunwald type II and III) who were admitted to our hospital
      between January 1998 and December 2000. The in-hospital and long-term prognosis
      was investigated in TnT-positive patients. In-hospital cardiac events were
      defined as death, myocardial infarction, heart failure and angina attacks during
      hospitalization. Long-term cardiac events were defined as death, myocardial
      infarction, heart failure and recurrence of angina. RESULTS: The incidence of in
      hospital cardiac events in all patients was 30.2%. The CRP levels were higher in
      patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057),
      but there was no significant difference between the two groups. The incidence of
      long-term cardiac events was 26.8%. The mean CRP level was significantly higher
      in patients with cardiac events than in patients without cardiac events (1.17 +/-
      1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1
      ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was
      47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive
      patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a
      markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and
      long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful
      in prediction of the long-term prognosis. TnT levels were useful in prediction of
      in-hospital prognosis. The present study suggested the possibility that the
      combined use of these biological markers could predict the prognosis of patients
      with unstable angina at early stage and more accurately.

PMID- 16637252
TI  - Assessment of atrial septal defect area changes during cardiac cycle by live
      three-dimensional echocardiography.
AB  - OBJECTIVES: To investigate the accuracy of measurement of the atrial septal
      defect (ASD)area and dynamic change by live three-dimensional echocardiography
      (L3DE). METHODS: L3DE was performed in patients with ASD using a three
      dimensional workstation to obtain the en face view of the ASD and measure its
      area at the peak of P-wave, the peak of R-wave, the initial and the destination
      point of T-wave, and the period of P-T. Parameters derived from L3DE were
      compared with intraoperative measurements. RESULTS: The ASD area changed
      significantly during cardiac cycles (mean change 46.1%, p < 0.0001; range 15.2
      72.5%), with the maximal area at endsystole and the minimal area at enddiastole.
      There was excellent correlation between L3DE and intraoperative measurements for
      the area of ASD at the peak of P-wave (r = 0.92). There were good correlations
      between the two methods during the other phases of cardiac cycle (r = 0.81-0.86).
      CONCLUSIONS: L3DE provides accurate and feasible measurements of the ASD area.
      Investigation of the dynamic changes during the cardiac cycle may lead to an
      improved understanding of the hemodynamics of ASD.

PMID- 16637253
TI  - Acute myocardial infarction induced by cisplatin-based combination chemotherapy
      for malignant melanoma: a case report.
AB  - A 61-year-old woman with stage IV malignant melanoma suffered acute myocardial
      infarction during the third course of chemotherapy with cisplatin, dacarbazine,
      nimustine hydrochloride and tamoxifen citrate, despite no serious problem
      occurring during the first and second courses of chemotherapy. Since this
      patient, excluding menopause, had no significant risk factor for coronary heart
      disease before the start of chemotherapy, the infarction was likely to be
      attributable to the chemotherapy regimen. Chemotherapy should be used cautiously
      in patients with coronary risk factors before treatment is begun.

PMID- 16637254
TI  - [Takotsubo-like left ventricular dysfunction with delayed recovery of left
      ventricular shape: a case report].
AB  - A 70-year-old woman was admitted to our hospital because of left ventricular
      dysfunction, which was observed after permanent pacemaker implantation in another
      hospital. The left ventricular dysfunction was apical ballooning. Left
      ventriculography demonstrated takotsubo-like shape. However, the dysfunction did
      not improve immediately with medical treatment. In this case, 75% stenosis was
      observed in the left anterior descending artery. We suppose that this lesion
      corresponded to the delayed recovery of the dysfunction and performed coronary
      intervention. The takotsubo-like shape improved gradually for about 1 year.
      Whether the coronary intervention was effective for the recovery of the
      dysfunction is unclear, this clinical course was interesting in evaluating the
      delayed recovery of takotsubo-like left ventricular dysfunction.

PMID- 16637255
TI  - Surgical treatment for Loffler's endocarditis with left ventricular thrombus and
      severe mitral regurgitation: a case report.
AB  - A 65-year-old female was admitted to our hospital because of dyspnea. Laboratory
      examinations revealed hypereosinophilia at a local hospital. Transthoracic and
      transesophageal echocardiography showed normal left ventricular dimension and
      function. The left ventricular apex was obliterated and the posterior and lateral
      walls were thickened by an abnormal mass. The posterior mitral leaflet was
      encapsulated by this abnormal mass. The limited motion of the posterior mitral
      leaflet caused mitral malcoaptation, resulting in severe mitral regurgitation.
      Hypereosinophilia was considered to be idiopathic, as no other disorders known to
      cause secondary eosinophilia were found. No other organ dysfunction was
      associated with the condition. Thus, the diagnosis was Loffler's endocarditis
      associated with hypereosinophilic syndrome. The patient was given conservative
      medical treatment immediately on admission. However, heart failure caused by
      mitral regurgitation would be difficult to treat with conservative medical
      treatment, so we chose a surgical strategy. The symptoms obviously improved after
      valve replacement and removal of the abnormal mass, and the patient was
      discharged. However, she died of cerebral infarction at a local hospital 3 months
      later.

PMID- 16637256
TI  - [Mobile mass attached to the tricuspid valve].

PMID- 16637257
TI  - Possible gender differences in the relationships of self-efficacy and the
      internal locus of control with compliance in hemodialysis patients.
AB  - In this study, the authors assessed gender differences between the relationships
      of self-efficacy and the internal health locus of control with compliance in
      hemodialysis patients. Using a self-efficacy scale for health-related behavior
      and the Japanese version of the Health Locus of Control Scale, the authors
      studied individuals who had been regularly undergoing hemodialysis for longer
      than 1 year. Blood urea nitrogen, serum potassium, and interdialytic weight gain
      were used to measure compliance. In men, self-efficacy and the internal health
      locus of control were negatively correlated with all compliance measures. In
      women, all the correlations were positive, except for that between self-efficacy
      and interdialytic weight gain. The authors constructed regression lines for the
      significant interactions. On the basis of blood urea nitrogen or serum potassium
      levels, the authors found that female patients who had higher self-efficacy or
      internal health locus of control were less compliant. The decrease of
      interdialytic weight gain accompanying increased self-efficacy was more
      significant in men than it was in women.

PMID- 16637258
TI  - The effects of stress and smoking on catecholaminergic and cardiovascular
      response.
AB  - In this study, the authors evaluated the combined impact of smoking and stress on
      catecholaminergic and cardiovascular reactivity in disease-free adult smokers.
      Smokers participated in 2 laboratory sessions, including a baseline and a mental
      stressor phase (reaction time and mental math), once while smoking-deprived
      overnight and once while nondeprived. Nonsmoking controls also participated in an
      identical laboratory session, without the smoking manipulation. The authors
      obtained cardiovascular measures during each phase and measured catecholamine
      levels immediately after each phase. For nondeprived smokers, measures of
      norepinephrine, epinephrine, heart rate, and systolic blood pressure (SBP) were
      larger for the mental-stressor phase than for the baseline phase. The authors
      found no such increases for deprived smokers, and only SBP increased for controls
      from the baseline phase to the mental-stressor phase. The results suggest that ad
      lib smoking increases catecholamine and cardiovascular response to stress in
      smokers.

PMID- 16637259
TI  - The role of illness beliefs, treatment beliefs, and perceived severity of
      symptoms in explaining distress in cancer patients during chemotherapy treatment.
AB  - The authors investigated cancer patients' interpretations of their physical
      symptoms and their illness beliefs with the objective of establishing the
      importance of these variables in predicting distress during chemotherapy
      treatment. Past researchers have suggested that causal attributions of physical
      symptoms and beliefs about illness progression and its consequences may serve as
      important mediators between number and perceived severity of symptoms and
      psychological adjustment in cancer patients during the treatment phase. Our aim
      in this study was to further these findings using the Self-Regulation Model as a
      theoretical framework. The study was cross-sectional in design, testing 72
      patients with cancer receiving intravenous chemotherapy as outpatients in the
      United Kingdom. The participants completed questionnaires measuring number and
      perceived severity of symptoms, the causal attributions of these, illness and
      treatment beliefs, anxiety, and depression. The results showed that consequence
      beliefs serve as important mediators between number of symptoms and distress,
      explaining 15% of the variance in anxious mood and 5% of the variance in
      depressed mood. The authors found perceived severity of symptoms to be an
      independent predictor of anxious mood, explaining 7% of the variance. Its role in
      predicting depressed mood was not significant.

PMID- 16637260
TI  - [Quorum sensing of genes expression--perspective drug target against bacterial
      pathogenicity].
AB  - Bacteria are capable to sense an increase of cell density population and to reply
      quickly and coordinately by the induction of special sets of genes. This type of
      the regulation was named Quorum Sensing (QS); it is based on the effect of low
      molecular-weight signaling molecules of different nature (autoinducers) which
      accumulate in the culture at high density of bacterial population and interact
      with receptor regulatory proteins. QS systems are the global regulators of
      bacterial genes expression and play a key role in the control of many metabolic
      processes in cell including the regulation of virulence of bacteria. Here we
      review the molecular mechanisms of QS systems functioning in bacteria belonging
      to different taxonomic groups and discuss the potential of QS regulation as a new
      drug target for the treatment of bacterial infections. At present this approach
      is accounted as a new alternative strategy of antimicrobial therapy directed on
      the development of drugs inhibiting QS regulation and active just against
      pathogenicity of bacteria (antipathogenic drugs). Such a strategy allows to avoid
      a wide dissemination of resistant forms of pathogenic bacteria and the formation
      of biofilms increasing in many times the resistance of bacteria to drug
      preparations.

PMID- 16637261
TI  - [Mismatch repair].
AB  - Specific repair systems are activated in response to the DNA damage. Mismatch
      repair protects the genome of prokaryotic and eukaryotic cells from lesions that
      appear during process of DNA replication or are induced by mutagenic factors. The
      methyl directed mismatch repair distinguishes the new strand from the old strand
      by the hemi-methylated state of the DNA and controls the fidelity of genetic
      information after homologous recombination. The very short patch repair restores
      the mismatches at the sites with nucleotide sequence CC(W/T)GG. The "8-oxoG"
      pathway is independent of the hemi-methylated state of the DNA, and removes the
      oxidated nucleotides from the genome of prokaryotes and eukaryotes. Mutations in
      genes of mismatch repair enhance the process of mutagenesis in prokaryotic cell,
      and are the reason for the development of the colon cancer in humans. The
      mechanisms of mismatch repair and the role of defective repair proteins in
      mutagenesis and carcinogenesis are discussed in this review.

PMID- 16637262
TI  - [Aberrant methylation of tumor suppressor genes and allelic imbalance in cervical
      intraepitelial neoplasia].
AB  - We analysed 42 high-grade CIN or CIN3 samples, 42 nondysplasia tissues adjacent
      to CIN3. 35 smears from women without gynecological pathology were also
      evaluated. Methylation status of six genes (p16, MLH1, HIC1, MGMT, N33 and RB1)
      was determined using methylation-sensitive PCR. There is some insignificant level
      of methylation determined in normal smears. Methylation percentages of the genes
      in CIN3 were: p16, 58%; MLH1, 51%; HIC1, 84%; N33, 27%. Methylation percentages
      of the genes in nondysplasia adjacent tissues were also high. There is no
      significant difference in methylation frequencies of MGMT and RB1 determined
      between dysplasia and control. We identified allelic imbalance at chromosomes
      5q11-q14 and 13q14 in 21% cases (9/42). The incidence of LOH was investigated in
      7% (3/42) cases at region 13q14.

PMID- 16637263
TI  - [Genotypes of vitamin-D-binding protein (DBP) in patients with chronic
      obstructive pulmonary disease and healthy population of Republic Bashkortostan].
AB  - The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene
      has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n
      = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and
      Russians) living in Republic Bashkortostan. Statistically significant differences
      in the distribution of DBP gene genotypes between Tatars and Russians (chi2 =
      8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution
      within DBP gene was similar in healthy control subjects of both ethnic groups,
      with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes
      were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been
      shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development:
      the frequency of GC*1F/1S genotype in COPD patients was significantly lower than
      in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor =
      0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the
      same group had higher frequency of GC* 1F/2 genotype than healthy individuals
      (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95%
      1.067-6.20). In Russian population the distribution of alleles and genotypes of
      DBP gene were similar in COPD patients and healthy individuals.

PMID- 16637264
TI  - [Relations between CTR1 gene activity and copper status in different rat organs].
AB  - CTR1 gene (SLC31A1 according to Entrez data base) product is the main candidate
      for the role of eukaryotic copper importer, whose tissue-specific function is
      still unclear. In this research steady state CTR1-mRNA level was measured with
      semiquantitative RT-PCR analysis and compared with copper status in rat organs,
      in which copper metabolism is changed during development (liver, cerebellum,
      choroid plexus and mammary gland). It has been shown that CTR1 gene activity
      correlates with the rate of both intracellular and extracellular copper
      containing enzymes formation. In mesenchymal origin cells of newborns the CTR1
      gene activity decreases when high copper concentrations in cell nucleus is
      reached. According to phylogenetic analysis CTR1 has the most conservative
      transmembrane domains 2 and 3 (TMD), containing 7 amino acid residues able to
      coordinate copper atom. A model of cuprophylic channel has been proposed, which
      is formed by TMD2 and TMD3 in homotrimeric CTR1 complex. In this model copper is
      transported through the channel to cytosolic C-terminal motif His-Cys-His, which
      ability to coordinate Cu(I) was assessed by molecular modeling (MM+, ZINDO/1).
      Theoretical possibility of copper transfer from His-Cys-His CTR1 C-terminal motif
      to cytosolic Cys-X-X-Cys Cu(I) chaperon sites has been shown. The role of CTR1 in
      copper metabolism as copper donor and acceptor is discussed.

PMID- 16637265
TI  - [A comparative analysis of tuberculosis susceptibility genetic make-up in
      Tuvinians and Russians].
AB  - The results of the first Russian study of polymorphisms of tuberculosis (TB)
      susceptibility genes SLC11A1, VDR, IL12B, IL1B, IL1RN in Tuvinians from Tuva
      Republic and Russians from Tomsk city are presented. In Tuvinians, as compared
      with Russians, the significantly higher prevalence of potentially disease
      associated alleles of the genes studied was shown: SLC11A1*543N (0.139 and 0.043,
      respectively, p = 4.6E-5), IL12B*1188C (0.378 and 0.174, respectively, p = 1.1E
      8), VDR*b (0.825 and 0.532, respectively, p = 3.2E-16), IL1B*(+3953A1) (0.865 and
      0.806, respectively, p = 0.035). However, no one of these alleles was associated
      with TB in Tuvinians, whereas, in Russians TB patients, in comparison with the
      controls, there was a higher prevalence of the following markers: IL1RN*A2 (0.258
      and 0.186, respectively, p = 0.024), SLC11A1*274T (0.251 and 0.164, respectively,
      p = 0.009), IL12B*1188C (0.240 and 0.174, respectively, p = 0.044),
      ILIB*(+3953A2) (0.259 and 0.194, respectively, p = 0.044). Distinct patterns of
      linkage disequilibrium between pairs of the polymorphisms studied in Tuvinians
      and Russians were shown. At whole, the data obtained demonstrate the ethnic
      specificity of the distribution and pathogenetic significance of the alleles of
      the TB susceptibility genes.

PMID- 16637266
TI  - [Association of polymorphisms in SULT1A1 and UGT1A1 Genes with breast cancer risk
      and phenotypes in Russian women].
AB  - Estrogens are critical for breast cancer initiation and development.
      Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1)
      conjugate and inactivate both estrogens and their metabolites, thus preventing
      estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 genes are both
      polymorphic, and different alleles encode functionally different allozymes. We
      hypothesize that low activity alleles SULT1A1*2 and UGT1A1*28 are associated with
      the higher risk for breast cancer and more severe breast tumor phenotypes. We
      performed a case-control study, which included 119 women of Russian ancestry with
      breast cancer and 121 age-matched Russian female controls. We used PCR, followed
      by pyrosequencing to determine SULT1A1 and UGT1A1 genotypes. Our data showed that
      UGT1A1*28 allele was presented at a higher frequency than the wild type UGT1A1*1
      allele in breast cancer patients as compared to controls (p = 0.002, OR = 1.79,
      CI 1.23-2.63). Consistently, the frequency of genotypes that contain the
      UGT1A1*28 allele in the homozygous or heterozygous state was greater than the
      frequency of the wild type UGT1A1*1/*1 genotype in breast cancer patients as
      compared to controls (p = 0.003, OR = 4.00, CI 1.49-11.11 and p = 0.014, OR =
      2.04, CI 1.14-3.57, respectively). The group of individuals, carrying the
      UGT1A1*28 allele in the homo- or heterozygous state also presented larger breast
      tumors (>2 cm) as compared to the group with high enzymatic activity genotypes p
      = 0.011, OR = 3.44, CI 1.42-8.36). No association was observed between any of the
      SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that
      UGT1A1 but not SULT1A1 genotype might be important for breast cancer risk and
      phenotype in Russian women.

PMID- 16637267
TI  - [Small heat shock proteins and adaptation to hypertermia in various Drosophila
      species].
AB  - Expression level and kinetics of accumulation of small heat shock proteins (21-27
      kDa group) have been investigated in three Drosophila species differing
      significantly by temperature niche and thermosensitivity. It was shown that low
      latitude thermotolerant species D. virilis exceeds the high-latitude
      thermosensitive closely-related species D. lummei as well as distant
      thermosensitive species D. melanogaster in terms of small heat shock proteins
      expression and accumulation after temperature elevation. The data obtained enable
      to postulate an important role of small heat shock proteins in organism basal
      thermotolerance and general adaptation to adverse conditions of environment.

PMID- 16637268
TI  - [Role of GroEL/GroES chaperonin system and Lon protease in regulation of
      expression Vibrio fischeri lux genes in Escherichia coli cells].
AB  - It was shown that the chaperonin GroEL/GroES and protease Lon influence the
      expression of the Vibrio fischeri lux regulon in Escherichia coli cells: E. coli
      groE mutants bearing hybrid plasmid with the lux regulon were weakly luminescent;
      cells of the E. coli lon- comprising the entire lux regulon display very intense
      bioluminescence, with no lag period in the induction curve characteristic of lon+
      strains. The luxR gene was cloned from the Vibrio fischeri genome in the pGEX-KG
      vector. It was shown that the active fusion protein GST-LuxR by affinity
      chromatography on glutathione-sucrose colony is purified only with proteins GroEL
      and Lon. The present results showed that the LuxR, transcriptional activator of
      the V. fischeri lux operon, really complexes with GroEL chaperonin and Lon
      protease. We suppose, that the GroEL/GroES chaperonin systems is required for the
      folding of LuxR into an active protein, and the LuxR is the target for the ATP
      dependent serine Lon protease of E. coli.

PMID- 16637269
TI  - [Native NC2 selectively represses incorrect transcription initiation].
AB  - Transcriptional regulation depends on the appropriate set of positive and
      negative signals that provide correct gene expression. Studies in eukaryotic gene
      expression have shown NC2 to be a general repressor of transcription which blocks
      the interaction between TFIIB and TBP. However, during the last few years NC2 has
      been found to bind the transcriptionally active promoters and interact with
      several positive transcription factors. These data suggested a controversial role
      of NC2 in transcription. Using in vitro transcription on minimal LTR promoter of
      HIV-1, we show that removal of NC2 from HeLa nuclear extract increases the yield
      of transcripts as well as unspecific transcription initiation in a template
      amount dependent manner. Fractions of HeLa nuclear extract containing NC2 can
      restore basal transcription repression and precise selection of transcription
      initiation point. This points to a new role for NC2 as a repressor of inaccurate
      transcription initiation that allows specific transcription to take place.

PMID- 16637270
TI  - [Glycosaminoglycanes biosynthesis connection with nuclear and microsomal cell
      apparatus].
AB  - The polysaccharides fractional composition was characterized in rat liver.
      Glycosaminoglycanes (GAG) anabolism was studied with the help of 14C1-glucose
      used as the synthesis precursor. It was demonstrated that GAG polysaccharide
      fragments synthesis began in the cell nucleus associated structures and finished
      in the microsomal cell fraction.

PMID- 16637271
TI  - [Features of interaction of complexes cortisol-apolipoprotein A-I and
      tetrahydrocortisol-apolipoprotein A-I with eukariotic DNA].
AB  - On primary culture of hepatocytes it is shown, that a complex cortisol
      apolipoprotein A-I did not change rate of biosynthesis DNA and protein, whereas
      the complex tetrahydrocortisol-apolipoprotein A-I (THC-apoA-I) essentially raised
      rate of incorporation 3H-thymidine in DNA and 14C-leucine into protein. By a
      method of small-angle X-ray scattering it is shown, that appreciable interaction
      with eukariotic DNA is marked only in case of use of a complex THC-apoA-I, thus
      there is local fusion of DNA. The most probable region of interaction of the
      given complex with DNA is repetition (GCC)n the type, included in structure of
      many genes eukariot, including the human. It is synthesized oligonucleotid
      (duplex) of this type. It is shown, that at his interaction with complex THC-apoA
      I there is a formation of more difficult complex, which breaks up with formation
      of complementary chains of oligonucleotides. The last also enter interaction with
      complex THC-apoA-I. It is given of kinetic this multiphasic process. Interaction
      of a complex cortisol-anoA-I with a duplex is less specific and does not result
      reduce in decay of the duplex and in formation of complementary oligonucleotides.

PMID- 16637272
TI  - [Influence of individual domains of the translation termination factor eRF1 on
      induction of the GTPase activity of the translation termination factor eRF3].
AB  - Translation termination in eukaryotes is governed by two proteins, belonging to
      the class-1 (eRF1) and class-2 (eRF3) polypeptide release factors. eRF3 catalyzes
      hydrolysis of GTP to GDP and inorganic phosphate in the ribosome in the absence
      of mRNA, tRNA, aminoacyl-tRNA and peptidyl-tRNA but needs the presence of eRF1.
      It's known that eRF1 and eRF3 interact with each other in vitro and in vivo via
      their C-terminal regions. eRF1 consists of three domains - N, M, and C. In this
      study we examined the influence of individual domains of the human eRF1 on
      induction of the human eRF3 GTPase activity in the ribosome in vitro. It was
      shown that none of the N-, M-, C- and NM-domains induces eRF3 GTPase activity in
      presence of the ribosomes. MC-domain does induce GTPase activity of eRF3 but four
      times less efficient than full-length eRF1, therefore, MC-domain (and very likely
      M-domain) binds to the ribosome in the presence of eRF3. Based on these data and
      taking into account the data available in literature, a conclusion was drawn that
      the N domain of eRF1 is not essential for eRF1-dependent induction of the eRF3
      GTPase activity. A working hypothesis is formulated, postulating that GTPase
      activity eRF3 during the translation termination is associated with the
      intermolecular interactions of GTP/GDP, GTPase center of the large ribosomal
      subunit (60S), MC-domain of eRF1, C-terminal region and GTP-binding domains of
      eRF3, but without participation of the N-terminal region of eRF3.

PMID- 16637273
TI  - [The specific cleavage of DNA with ultrasound].
AB  - Cleavages of double-stranded DNA fragments of known base pair sequence upon
      ultrasound irradiation at 22 and 44 kHz were studied by gel electrophoresis. The
      cleavage rate is found to be strongly dependent on the DNA fragment length, pH,
      temperature and ionic strength of the solution under study. The cleavage of
      double-stranded DNA occurs predominantly at sites containing alternating 5'-CpG
      3' sequences. The breakage of phosphatediester bond takes place between C and G
      in such a way that phosphate group at the 5'-end of the guanine residue remain
      intact. The cleavage rate at a given DNA site is found to depend on base pair
      sequences at adjacent sites. Distinctly different cleavage patterns are observed
      when free DNA and DNA complexes with cys-diammine-Pt-bridged bis-netropsin were
      irradiated by ultrasound. The observed effect can be attributed to local DNA
      conformation changes induced upon complex formation between ligand and DNA.

PMID- 16637274
TI  - [The conformational dynamic of the tetramer hemoglobin molecule as revealed by
      hydrogen exchange. I. Influence pH, temperature and ligand binding].
AB  - The rate of the H-D exchange of the peptide NH atoms of the different forms of
      human Hb was studied at the range of pH 5-10 and temperature 10-63 degrees C by
      the IR spectroscopy. The pH-dependence of the H-D exchange rate is accordance
      with the EX2 mechanism. Two pH-dependent conformers of ligand forms of Hb existes
      at 10-30 degrees C with lower probability of local fluctuations of the alkaline
      conformer. The difference between two conformers vanishes at 40 degrees C with
      the appearance of the third conformer with higher probability of local
      fluctuations. The deoxyHb at 20 degrees C and pH range 6-9 has no pH-dependent
      conformers and the probability of local fluctuations is considerably reduced in
      comparison to the acid conformer of ligand Hb. Upon the destabilization of the
      ligand Hb structure by the pH decreasing to 5.0 at 20 degrees C or the
      temperature increasing up to 50-60 degrees C at pH 7.1 the global fluctuations of
      the native structure are intensified providing the H-D exchange of the slowest
      exchanging NH atoms. The nature of the local and global fluctuations and possible
      similarity between the two pH-dependent conformers of ligand Hb and its
      functional R and R2 states revealed by the X-ray analysis and NMR spectroscopy
      were discussed.

PMID- 16637275
TI  - [Prediction of natively unfolded regions in protein chain].
AB  - We have shown that the ability of a protein to be in globular or in natively
      unfolded state (under native conditions) may be determined (besides low overall
      hydrophobicity and a large net charge) by such a property as the average
      environment density, the average number of residues enclosed at the given
      distance. A statistical scale of the average number of residues enclosed at the
      given distance for 20 types of amino acid residues in globular state has been
      created on the basis of 6626 protein structures. Using this scale for separation
      of 80 globular and 90 natively unfolded proteins we fail only in 11% of proteins
      (compared with 17% of errors which are observed if to use hydrophobicity scale).
      The present scale may be used both for prediction of form (folded or unfolded) of
      the native state of protein and for prediction of natively unfolded regions in
      protein chains. The results of comparison of our method of predicting natively
      unfolded regions with the other known methods show that our method has the
      highest fraction of correctly predicted natively unfolded regions (that is 87%
      and 77% if to make averaging over residues and over proteins correspondingly).

PMID- 16637277
TI  - [Epitope mapping of antigenic determinants of hepatitis C virus proteins by phage
      display].
AB  - Study of individual hepatitis C (HCV) proteins could help to find a molecular
      structure and conformation, localization of antigenic and immunogenic
      determinants, to reveal of protective epitopes. It is necessary for practical
      medicine - development of diagnostic test-systems, vaccines and therapeutics.
      Linear and conformation dependent epitopes of HCV proteins was localized in this
      work and immunogenic properties of phage displayed peptides screened on
      monoclonal antibodies to HCV proteins have been investigated. Eleven epitopes of
      four HCV proteins have been studied. Three epitopes was found as linear, two
      epitopes were dependent on secondary structure of proteins and one epitope was
      dependent on tertiary structure of NS3 protein. Aminoacid sequences of other
      determinants have been determined and the distinct localization of these
      determinants will be continued after discovering of tertiary structure of HCV
      proteins. It was shown, that phage mimotope 3f4 is immunogenic and could induce
      specific hu- moral immune response to NS5A HCV protein. The data obtained could
      be useful for improving of HCV diagnostic test-systems, studying of amino acid
      substitutions and its influence on antigenic properties of the HCV proteins. The
      results could help to study an immune response in patients infected with
      different genotypes of HCV. Phage displayed peptides mimicking the antigenic
      epitopes of HCV proteins could be applied to development of HCV vaccine.

PMID- 16637276
TI  - [Characterization of the universal Russian reagent sets for real-time PCR and its
      application for molecular oncodiagnostic].
AB  - Universal Russian reagents for real time PCR were tested and compared with
      reference reagents provided by foreign companies. Testing was carried out on
      plasmids with cloning fragments (DNA-standards) of cDNA with chimeric (fusion)
      gene PML-RARalpha. Values of amplification efficiency of Russian and foreign
      reagents were measured on samples with serial dilutions (30-300000 copies) of
      cloned cDNA fragments of PML-RARalpha and internal control gene ABL.
      Amplification efficiencies of Russian and foreign reagents were found to be close
      one to another. Russian universal reagent kit RealityTM and ABI TaqMan Core
      Reagent Kit have amplification efficiencies 1.919 and 1.929, and correlation
      coefficients of copy numbers PML-RARalpha0.999 and 0.996, respectively. These
      values were determined by construction of a standard curve. To verify these
      results we studied also the samples of cDNA from blood and bone marrow of
      patients with acute promyelocytic leukemia. All samples posses translocation
      t(15;17), and appropriate chimeric gene PML-RARalpha. copy number in 1 microg of
      total RNA was in range 5.86 x 10(4)-8.315 x 10(5) before chemotherapy. No
      symptoms of minimal residual disease were found after 3.5 months since
      chemotherapy - fusion gene PML-RARalpha was not detected by real time PCR method.
      These results are in agreement with clinical data. Our investigations tend to
      show that application of RealityTM reagent set in real timePCR experiments gives
      correct results and may be used in molecular oncodiagnostics.

PMID- 16637278
TI  - [The importance of recombinations occuring in the process of DNA replication].
AB  - In the process of DNA replication in Escherichia coli, the unequal crossing over
      occurs between DNA direct repeats in sister chromosomes. Such exchanges lead to
      the formation of tandem duplications and, therefore, to an increase of gene
      expression. It is proposed that non-homologous cohesion of sister chromosomes and
      unequal crossing over occur if the movement of replication fork is stopped. In
      the case of the unceasing movement of replication fork the homologous exchange
      between sister chromosomes occurs which provides their post-replication
      reparation.

PMID- 16637279
TI  - [Characterization of Mn- and Cu/Zn-containing superoxide dismutase gene
      transcripts in Larix gmelinii].

PMID- 16637280
TI  - [New genes coding for vitelline membrane proteins in Drosophila].

PMID- 16637281
TI  - [A new family of interspersed repeats from squamate reptiles].

PMID- 16637282
TI  - [Natural alpha-conotoxins and their synthetic analogues in studies of nicotinic
      acetylcholine receptors].
AB  - alpha-Conotoxins, peptide neurotoxins from poisonous marine snails of the genus
      Conus that highly specifically block nicotinic acetylcholine receptors (AChRs) of
      various types, are reviewed. Preliminarily, the structural organization of AChRs
      of the muscular and neuronal types, their involvement in physiological processes,
      and their role in various diseases are briefly discussed. In this connection, the
      necessity of quantitative determination of AChR subtypes using neurotoxins and
      other approaches is substantiated. The chemical structure, spatial organization,
      and specificity of alpha-conotoxins are mainly discussed, taking into
      consideration the recent results on the ability of alpha-conotoxins to interact
      with muscular or neuronal hetero- and homooligomeric AChRs exhibiting a high
      species specificity. Particular emphasis is placed upon a thorough
      characterization of the surfaces of interaction of alpha-conotoxins with AChRs
      using synthetic analogues of alpha-conotoxins, mutations in AChRs, and pairwise
      mutations in both alpha-conotoxins and AChRs. The discovery in 2001 of the
      acetylcholine-binding protein from the pond snail Lymnaea stagnalis and the
      determination of its crystalline structure led to rapid progress in understanding
      the structural organization of ligand-binding domains of AChRs with which alpha
      conotoxins also interact. We discuss the interaction of various alpha-conotoxins
      with acetylcholine-binding proteins, the recently reported X-ray structure of the
      complex of the acetylcholine-binding protein from Aplysia californica with the
      alpha-conotoxin analogue PnIA, and the application of this structure to the
      modeling of complexes of alpha-conotoxins with various AChRs.

PMID- 16637283
TI  - [Native and modified subtilisin Karlsberg as an effective catalyst of peptide
      bond formation in organic media].
AB  - The activity and stability of native subtilisin Karlsberg and subtilisin 72 and
      their complexes with sodium dodecyl sulfate (SDS) in organic solvents were
      studied. The kinetic constants of the hydrolysis of specific chromogenic peptide
      substrates Z- ALA-Ala-Leu-pNA and Glp-Ala-Ala-Leu-pNA by the subtilisins were
      determined. It was found that the subtilisin Karlsberg complex with SDS in
      anhydrous organic solvents is an effective catalyst of peptide synthesis with
      multifunctional amino acids in positions P1 and P'1 (Glu, Arg, and Asp)
      containing unprotected side ionogenic groups.

PMID- 16637284
TI  - [The structure-antiaggregative activity relationship in a series of Arg-Gly-Asp
      analogs].
AB  - A series of analogues of Arg-Gly-Asp tripeptide, the common structural element of
      most of the integrin receptor ligands, possessing different conformational
      features for the interaction with platelet receptors, were synthesized by the
      methods of conventional peptide chemistry for use in the search for
      antithrombotic agents. The distance between the guanidine group of Arg and the
      beta-carboxyl group of Asp was shown to affect the antiaggregative activity. A
      potent inhibitor of platelet aggregation, tripeptide Arg-betaAla-Asp, with IC50 =
      10.6 microM (ADP, 1.5 microM), was revealed.

PMID- 16637285
TI  - [Synthesis of modified fragments of fibrinogen and their effect on the activity
      of proteolytic enzymes].
AB  - New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were
      synthesized: Gly-Pro-Arg-Pro (I), Gly-Pro-Arg-Pro-Met-OMe (II), Gly-Pro-Arg-Pro
      Phe (III), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp
      (VI). Their effect on the activity of proteases of various types was studied with
      the method of lysis of fibrin plates. All the peptides were found to inhibit
      plasmin activity (by 60-85%) and the gamma-subunit of nerve growth factor (by 55
      93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator
      of plasminogen and the gamma-subunit of nerve growth factor (by 96 and 93%,
      respectively). The peptides exerted practically no effect on the activity of
      urokinase and moderately inhibited the activity of streptokinase [(III), (IV),
      and (VI)], papain [(I), (II), (IV), and (VI)], subtilisin [(V) and (VI)], alpha
      chymotrypsin [(III), (V), and VI)], and Bacillus subtilis metalloprotease (VI).
      They inhibit trypsin [except for (I) and (III)] when applied on fibrin plates at
      a concentration of 1 x 10(-2) M, while, at a concentration of 1 x 10(-3) M, (I)
      and (II) induced an increase in proteolytic activity by 35 and 47%, respectively.

PMID- 16637286
TI  - [The synthesis of immunomodulating peptide alloferon, the active component of the
      antiviral drug allokine-alpha].
AB  - Two variants of the synthesis of tridecapeptide alloferon, the active principle
      of antiviral preparation allokine-alpha, were developed on the basis of fragment
      condensation in solution or on the Merrifield resin. The solid phase variant of
      the synthesis was shown to be more technological; it allows the preparation of
      the product at a higher total yield (40% vs. 17% for conventional synthesis in
      solution from the starting derivatives of the C-terminal dipeptide). The by
      products formed during the synthesis of alloferon were identified.

PMID- 16637287
TI  - [Peptide fragment 66-77 of monocyte chemoattractant protein 1 and its retro
      enantio analogue inhibits the migration of cells in vitro and in vivo].
AB  - The retro-enantio analogue of peptide 66-77 of the chemokine MCP-1 and two
      hexapeptide fragments 66-71 and 72-77 of the C-terminal sequence of this protein
      were synthesized using the Fmoc strategy of solid phase peptide synthesis. The
      effect of the synthetic peptides upon the MCP-1-stimulated migration of THP-1
      mononuclear cells was studied in vitro. The activity of the retro-enantio
      analogue was found to be comparable with that of the initial peptide 66-77: both
      peptides inhibit the migration of monocytes and granulocytes into inflammation
      zones of experimental animals.

PMID- 16637288
TI  - [Production of antibodies to the alpha7-subunit of human acetylcholine nicotinic
      receptor with the use of immunoactive synthetic peptides].
AB  - Potential B epitopes and T-helper epitopes in the N-terminal extracellular domain
      of the alpha7-subunit of human acetylcholine receptor (AChR) were theoretically
      calculated in order to reveal peptides that can induce the formation of specific
      antibodies to this domain. Four peptides structurally corresponding to four
      alpha7-subunit regions containing 16-23 aa and three of their truncated analogues
      were synthesized. Rabbits were immunized with both free peptides and protein
      conjugates of their truncated analogues, and a panel of antibodies to various
      exposed regions of the N-terminal extracellular domain of the AChR alpha7-subunit
      was obtained. All of the four predicted peptides were shown to induce the
      production of antipeptide antibodies in free form, without conjugation with any
      protein carrier. The free peptides and the protein conjugates of truncated
      analogues induced the formation of almost equal levels of antibodies. Most of the
      obtained antisera contained antibodies that bind to the recombinant extracellular
      N-terminal domain of the rat AChR alpha7-subunit and do not react with the
      analogous domain of the alpha1-subunit of the ray Torpedo californica AChR.

PMID- 16637289
TI  - [Interaction of delta sleep-inducing peptide and its analogues with cellular
      membranes: a structure-function analysis].
AB  - The possibility of a correlation between the membrane properties of the delta
      sleep-inducing peptide (DSIP) and its analogues and their biological activity in
      vivo was examined by a comparative study of the membrane effects of these
      peptides. The peptides exhibiting biological activity in vivo were shown to cause
      a statistically reliable disordering of lipids in thrombocyte plasma membranes
      similar to the effect of DSIP. The membrane effect of the D-Val2, D-Tyr2, and
      Tyr1, Pro2 analogues of DSIP had the same bimodal dose dependence characteristic
      of natural DSIP. Only a slight nonspecific lipid disordering was registered for
      Trp-Asp-Ala-Ser-Gly-Glu, a biologically inactive hexapeptide analogue. These
      results indicate a correlation between the biological activity of the peptides
      during in vivo tests and their membrane properties in vitro. The structure
      function relationship was studied within the group of DSIP analogues examined in
      vitro. The DSIP modeling effect, especially pronounced under the action of stress
      factors, was suggested to be directly associated with the ability of DSIP to
      change the dynamic structure of biological membranes.

PMID- 16637290
TI  - [Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation].
AB  - Biologically active peptides evenly labeled with tritium were used for studying
      the in vitro and in vivo biodegradation of the peptides. Tritium-labeled peptides
      with a specific radioactivity of 50-150 Ci/mmol were obtained by high temperature
      solid phase catalytic isotope exchange (HSCIE) with spillover tritium. The
      distribution of the isotope label among all amino acid residues of these peptides
      allows the simultaneous determination of practically all possible products of
      their enzymatic hydrolysis. The developed analytical method includes extraction
      of tritium-labeled peptides from organism tissues and chromatographic isolation
      of individual labeled peptides from the mixture of degradation products. The
      concentrations of a peptide under study and the products of its biodegradation
      were calculated from the results of liquid scintillation counting. This approach
      was used for studying the pathways of biodegradation of the heptapeptide TKPRPGP
      (Selank) and the tripeptide PGP in blood plasma. The pharmacokinetics of Selank,
      an anxiolytic peptide, was also studied in brain tissues using the intranasal in
      vivo administration of this peptide. The concentrations of labeled peptides were
      determined, and the pentapeptide TKPRP, tripeptide TKP, and dipeptides RP and GP
      were shown to be the major products of Selank biodegradation. The study of the
      biodegradation of the heptapeptide MEHFPGP (Semax) in the presence of nerve cells
      showed that the major products of its biodegradation are the pentapeptide HFPGP
      and tripeptide PGP. The enkephalinase activity of blood plasma was studied with
      the use of evenly tritium-labeled [Leu]enkephalin. A high inhibitory effect of
      Semax on blood plasma enkephalinases was shown to arise from its action on
      aminopeptidases. The method, based on the use of evenly tritium-labeled peptides,
      allows the determination of peptide concentrations and the activity of enzymes
      involved in their degradation on a tg scale of biological samples both in vitro
      and in vivo.

PMID- 16637291
TI  - [Short peptide fragments with antiulcer activity from a collagen hydrolysate].
AB  - A peptide acidic hydrolysate of collagen (PHC) was obtained under conditions (4 N
      HCl) ensuring the predominant formation of short peptides, glyprolines. They were
      separated and their antiulcer activity was studied. Thirty individual peptides
      with molecular masses of 174-420 amu were isolated from the PHC by HPLC. The PHC
      was shown to predominantly contain 2- to 4-aa peptides, including PG, GP, and
      PGP. Experiments on rats demonstrated that, on intragastric administration at a
      dose of 1 mg/kg, PHC enhances the stability of the gastric mucosa to the action
      of ulcerogenic factors, such as ethanol and stress, and exhibits a protecting
      antiulcer effect. Even a lesser dose (0.1 mg/kg), which reduced ulcer area
      twofold, was effective in the stress model of ulcer formation. The
      intraperitoneal and intragastric administration of PHC at a dose of 1 mg/kg was
      found to exhibit a therapeutic effect in the acetate model of ulcer formation.

PMID- 16637292
TI  - [Synthesis and structure-function study of artificial nucleases on the basis of
      hemin conjugates with peptide fragments of cell differentiation factor HLDF].
AB  - A series of octa-hexapeptide fragments of HLDF and their conjugates with hemin
      were obtained by solid phase peptide synthesis. A relationship between the
      structure and the nuclease activity of the compounds was established. The effect
      of various factors (medium pH, the presence of metal ions, complexons, reducers,
      and buffer composition) on DNA destruction with hemin peptides was studied.
      Preliminary information confirming an oxidative mechanism of this process was
      obtained. The cleavage of plasmid DNA under the action of hemin peptides was
      studied by the methods of electron microscopy, gel electrophoresis, and atomic
      force microscopy.

PMID- 16637293
TI  - [Isolation and structure of peptides from oat (Avena sativa) seedlings].
AB  - The level of proteolytic activity in tissues of oat seedlings was characterized
      under acidic conditions, and the number and content of the main components in low
      molecular-mass fractions of the extract were determined. The structures of the
      majority of predominant peptide components isolated from the extract were
      studied. The use of a database of protein structures helped suggest possible
      structures of protein precursors of the peptides isolated. Detailed information
      on a plant peptidome was obtained for the first time.

PMID- 16637294
TI  - [Cytotoxic steroids with antiestrogenic activity of the 11alpha-acyloxyestra
      1,3,5(10)-triene series].
AB  - Esterification of 3-hydroxyl group in 11-acyloxyestra-1,3,5(10)-trienes with p
      [bis(2-chloroethyl)amino]phenylacetic acid led to antitumor steroids displaying
      antiestrogenic and cytotoxic activities. Our substances exhibit their activities
      on the model of murine mammary adenocarcinoma Ca-755, with inhibition of the
      tumor growth being 94-99%. A new approach was used for the 11alpha-hydroxylation
      of estra-1,3,5(10)-trienes.

PMID- 16637295
TI  - [Doppler velocimetry in patients with preeclampsia].
AB  - Doppler velocimetry is a fast and convenient method for monitoring of fetal well
      being in high risk pregnancies. Doppler velocimetry is more specific and
      sensitive method of fetal surveillance than cardiotocography. The study's
      objective is to prove Doppler's effectiveness in predicting perinatal outcome in
      preeclamptic pregnancies. A retrospective study is designed, including pregnant
      women, diagnosed with preeclampsia, admitted to Maternity hospital "Majchin dom"
      for ten years. Doppler study was made and results were correlated to Apgar score,
      umbilical artery pH and base excess of the neonate at delivery. A correlation
      between RI of umbilical artery, uterine arteries and Apgar score at 5th minute
      was demonstrated. In severe cases correlation between RI of umbilical artery and
      neonatal pH was found. CONCLUSION: Doppler velocimetry is an effective method of
      fetal surveillance in pregnancies, complicated by preeclampsia

PMID- 16637296
TI  - [Assessment of Bishop's pelvic score in induction of labor prognosis].
AB  - Aim of the present mixed prospective and retrospective study is to determine the
      prognostic significance of the 5 parameters of the pelvic score of Bishop for the
      continuity and the final outlet of induction of labor. Based on the given results
      the authors conclude that the dilatation of the cervix is a good prognostic
      factor for the nulliparous and bad prognostic factor for multiparous. The
      effacement of the cervix is significant for the outlet of the induction
      regardless of parity. The level of the presenting part is a valuable criterion
      for the nulliparous when the pelvic is well assessed but for the multiparous it
      has no prognostic value. The firmness of the cervix has a bad prognostic value
      regardless of parity. The position of the is a good prognostic factor for the
      outlet of the induction but has no value prognosis of the continuity of the
      induction.

PMID- 16637297
TI  - [Pregnancy in teenagers].
AB  - Teenage pregnancy is a recognized problem of social and health significance
      worldwide. World Health Organization considers them as high-risk pregnancies.
      Teenage birth rates vary by different country. OBJECTIVE: To study the frequency
      and the obstetric outcome of pregnancy at teenagers in University Hospital "St.
      George" Plovdiv. SUBJECTS AND METHODS: Nuliparous women who at the period of the
      delivery were at 11-19 years old and were seen at the obstetric unit of the above
      hospital were recruited into the study. Observed complications during the
      pregnancy and delivery were also calculated. RESULTS: For the period of 10 years
      the teenage pregnancy rate was 8.22%/n= 958/ of all 11657 deliveries /91.78%/.
      901 of the teenagers were aged 16 to 19 years /7.73%/ while only 57/0.49%/ were
      aged 11 to 15 years. In 69.42% /n= 665/ of the cases the deliveries were not
      complicated; in 30.58% of the cases there were complications or the delivery
      ended surgicaly. CONCLUSIONS: Pregnancy during teenage years remains major public
      health problem with lasting repercussions for the teenage mothers and their
      infants but also for their families and society as a whole. The prevention of the
      adolescent pregnancy by executing proven and effective programs would decrease
      its frequency and the complications associated with it.

PMID- 16637298
TI  - [Trophoblast expression of EGFR (epidermal growth factor receptor) in the
      preeclampsia placenta].
AB  - Placental pathology in preeclampsia and retarded fetuses is associated with
      changes of the pattern of expression of EGFR. The purpose of this study was to
      investigate the expression of epidermal growth factor receptor in trophoblast
      populations of preeclampsia and retarded fetuses in comparison with normal
      controls. Tissue microarray with paraffin sections containing a general of 90
      placental specimens including 30 preeclamptic cases, 30 retarded fetuses and 30
      normal pregnancies (controls) were studied immunohistochemically for epidermal
      growth factor receptor in the syncytiotrophoblast and villous cytotrophoblast.
      Epidermal growth factor receptor levels were estimated semiquantitatively. The
      percentage of strong/intermediate immunoreactivity of epidermal growth factor
      receptor in the syncytiotrophoblast was significantly higher in normal placental
      cases (98%) than in pathological conditions (P = .03), although
      strong/intermediate immunoreactivity in the syncytiotrophoblast was significantly
      lower in pathologic cases (35%) than controls (P < .001). No correlation (P >
      0.01) was found between the trophoblast expression of EGFR and the weight of the
      newborn fetuses. Epidermal growth factor receptor expression in the villous and
      extravillous cytotrophoblastic cells were significantly different between
      controls and preeclamptic cases (P > .05). CONCLUSION: The development of
      pathologic pregnancies is possibly related to the differential expression of
      epidermal growth factor receptor in the syncytiotrophoblast.

PMID- 16637299
TI  - [Screening of asympthomatic patients for chlamydia trachomatis infection in
      Sofia].
AB  - In order to evaluate the prevalence of Chlamydia infection in asymptomatic
      patients, 568 materials were analyzed. Analysis were performed among women and
      men aged 16 - 45 years. The observed prevalence rate is 5.5% and is similar to
      the prevalence reported for other European countries. Our study demonstrates that
      the prevalence of asymptomatic Chlamydia infection in Sofia is low.

PMID- 16637300
TI  - [The role of the preoperative radiochemotherapy and the role of neoadjuvant
      chemotherapy before radical Wertheim-Meigs hysterectomy for cervical cancer stage
      I B - II B].
AB  - One of the most important prognostic factors for early stages cervical cancers is
      the tumour size. The patients with size of the tumour bigger than 4 sm in
      diameter have worse prognosis. The aim of our research work was to compare the
      efficacy of preoperative radiochemotherapy and neoadjuvant intravenous
      chemotherapy, followed by radical hysterectomy a modo Wertheim-Meigs for stage I
      B - II B cervical cancer. We summerized our and foreign experience in this field.
      From 1998 till 2005 we examined 123 patients in stage I B - II B cervical cancer
      treated by preoperative percutaneous radiotherapy (dosis 45 Gy) plus cisplatin
      (50 mg/m2) compared with preoperative chemotherapy cisplatin (50 mg/m2),
      vincristin 1 mg/m2 every 7-10 days for 3 courses. Radical hysterectomy a modo
      Wertheim-Meigs was performed 4-5 weeks after the preoperative treatment. There is
      no significant difference in the age groups, stages of the tumour, the tumour
      size end the histopathological kind of the tumour between the 2 groups of
      examined patients. The toxicity in the two groups was mild. In the group with
      preoperative radiochemotherapy 4 patients developed vesicovaginal fistulas, 3
      patients hydronephrosis. After the surgical treatment the invasion of the tumour
      in the parametrial region and the lymph nodes was without any significant
      difference between the two groups (p>0.06). In the group with neoadjuvant
      chemotherapy more patients had a residual tumour, but about the size of the
      tumours in the two groups there was no significant difference (p>0.05). The final
      pathological response was higher in the group received radiochemotherapy.
      Acording to the results of our research work the neoadjuvant chemotherapy and the
      radiochemotherapy have nearly equal effect on the prognostic factors connected
      with survival.

PMID- 16637301
TI  - [Endoscopic treatment of pelvic inflamatory disease].
AB  - The authors present their own attempt of miniinvasive management of pelvic
      inflammatory disease. Two groups of patients are compared--in the first one the
      women are treated only conservatively, while the second one has undergone
      miniinvasive surgical treatment. The preferences of combined therapy are pointed
      out.

PMID- 16637302
TI  - [Fibroblastic and myofibroblastic lesions of the breast--clinical and
      morphological aspects].
AB  - Fibroblastic and myofibroblastic lesions are challenging because they occur
      infrequently and there is significant clinical, radiologic and morphologic
      overlap between reactive and neoplastic lesions, as with non-fibrous lesions. In
      this article we describe and discuss four particular entities in some detail:
      fibromatosis of the breast, nodular fasciitis, pseudoangiomatous stromal
      hyperplasia of the breast and one case of mammary type myofibroblastoma.

PMID- 16637303
TI  - [The effect of contraceptive with 20 ug ethinylestradiol and 150 ug desogestrel
      on some acute phase proteins].
AB  - BACKGROUND: We present the influence of monophasic combined oral contraceptive
      with 20 mmicrog ethinylestradiol /150 microg desogestrel upon some acute phase
      proteins: C- reactive protein, fibrinogen, haptoglobin and the connection between
      the proinflammatory effect of oestrogens METHODS: Forty clinically healthy young
      women between 18 and 35 years, using oral contraceptives in the duration of 12
      months, are included in this study. RESULTS: We don't find statistically
      significant differences in the plasma concentrations of C--reactive protein,
      fibrinogen, haptoglobin on the 12th month of the using of the oral contraceptives
      in comparision with the initial levels of the variables, before starting the
      study. CONCLUSION: The reduction of the dose of ethinylestradiol, definitely
      reduces the effects of oral contraceptives upon acute phase proteins and
      eventually the increased risk of cardiovascular disease.

PMID- 16637304
TI  - [Modern aspects of perioperative analgesia by using nonsteroidal anti
      inflammatory drugs in gynecology (Part II)].
AB  - It is an actual problem how to treat acute postoperative pain by using
      nonsteroidal anti-inflammatory drugs. Modern concepts for perioperative
      administration of these drugs are very important for the usual practice. The
      possibilities for optimal application of nonselective or selective COX-2
      inhibitors are examined in this review.

PMID- 16637305
TI  - [Phlebothrombosis and thrombophlebitis during the second half of pregnancy and
      puerperium].
AB  - Fhlebothrombosis and thrombophlebitis of the cerebral veins and sinuses develop
      relatively rare, but they affect young people and have poor prognosis. Pregnancy
      and puerperium are et risk due to hormonal and homeostatic changes in the
      organism. This report exhibits the most frequent etiologic factor, early
      symptoms, clinical manifestation, diagnostic value of the different methods,
      treatment principals and the factors that determine the outcome of
      thrombofphlebitis and phlebothrombosis during pregnancy and puerperium. In the
      acute phase a treatment with direct anticoagulants (intravenous heparin or low
      molecular mass heparins) and symptomatic treatment with anticonvulsants and drugs
      against oedema. After the acute phase the treatment continues with oral indirect
      anticoagulant as long as the severity of the disease requires.

PMID- 16637306
TI  - [Magnetic resonance imaging--diagnosis and differential diagnosis of tumor
      formations (cyst) in the abdomen cavity during pregnancy].
AB  - The existence of tumor formations with unidentified origin in the abdomen cavity
      of the pregnant can cause serious problems during the operative intervention. It
      is critical to find the organ origin of the existing formation and it's relations
      with the neighboring organs. In the following article we present some of the
      capabilities of the magnetic resonance tomography as a complementally to the
      existing in the clinical practice classical and special methods for diagnosis and
      differential diagnosis of tumor formations in the abdomen cavity during
      pregnancy. MRI locates precisely the organ origin, the type and the size of the
      cyst formation, furthermore it helps to determine in detail the access point, the
      type and size of the operative intervention. The technique is harmless concerning
      the pregnancy and the development of a normal, healthy fetus.

PMID- 16637307
TI  - [A case report of two incidents of acute abdomen in a woman during pregnancy and
      in the early puerperium].
AB  - The authors present a case of a 32 year old pregnant woman who is admitted to the
      Obstetric clinic in the 16th gestational week with a pain in the ileoceacal
      region of the abdomen and vomitting. The woman has clinical signs of acute
      abdomen. A clinical diagnosis of acute appendicitis was suggested. During the
      operation under general anesthesia was found a phlegmonous inflammation of a
      Mekel diverticulus with perforation as well as local peritonitis and a catharal
      inflammation of the appendix. The appendix and the Mekel diverticle were removed
      during the operation. No comlications were observed during the post operative
      period. No fetal distress was observed during and after the operation Three
      months later the same patient was admitted to the obstetric clinic in the 32nd
      gestational week with a diagnosis Threatened premature delivery in ml VIII status
      post resection of a Mekel diverticle and appendectomy. The patient had pain to
      the right of the umbilicus and vomiting. The labor was induced and a viable
      premature infant was born. Two days after delivery there was again a clinical
      symptoms and signs of an acute abdomen due to ileus. A strangulation of the
      terminal ileum was found due to adhesions A Debridman and a lavage were performed
      No complications were observed during the postoperative period. The authors
      discuss the difficulties which might ensue when the diagnosis acute abdomen is
      made in a pregnant woman

PMID- 16637308
TI  - [Cryopreservation of umbilical cord blood. Technological aspects].
AB  - Umbilical cord blood, derived from the umbilical cord at the time of delivery, is
      a rich source of haemopoietic stem cells and has been used successfully in the
      treatment of various diseases. Worldwide until now, more than 200,000 umbilical
      cord blood units have been cryopreserved and more than 5000 transplantations have
      been undergone. The basic technics for preparation, cryopreservation and storing
      of the material before transplantation have been represented.

PMID- 16637309
TI  - [Effect of the blood pressure on the perinatal fetal outcome in patients with
      preeclampsia].
AB  - No matter the fact that the changes in the blood pressure are quite often the
      first clinical feature of preeclampsia, is known that they are not early, but are
      quite late preeclampsia symptom. Close follow-up of the blood pressure trough
      whole pregnancy and in preeclamptic patients plays an important role in the
      improvement of the perinatal outcome. Five hundred forty four singleton pregnant
      women were enrolled in the study. Of them 334 were with mild preeclampsia and 210
      were with severe form of the disease. The analysis of correlations shows a
      correlation between the blood pressure at admititon and before delivery of the
      women with mild and severe form of preeclampsia and the perinatal fetal outcome.
      The fifth minute Apgar score is significantly lower in the patients with severe
      preeclampsia in comparison with women with mild disease. The represented data
      confirm the hypothesis about the influence of the maternal blood pressure on the
      perinatal fetal outcome.

PMID- 16637310
TI  - [Pregnancy outcomes in women of advanced maternal age].
AB  - During the last decade there is a trend all over the world women at advanced
      age/older than 35 years old/ and especially educated ones to postpone their
      reproductive plans. Pregnancy and birth outcomes in women >35 years old I
      traditionally associated with increasing risk of complications both for the
      mother and the foetus. OBJECTIVE: To study the frequency and the obstetric
      outcome of pregnancy at advanced age women in the University Hospital "St.
      George" Plovdiv. SUBJECTS AND METHODS: Women who at the period of the delivery
      were at more than 35 years old and were seen at the obstetric unit of the above
      hospital were recruited into the study. Observed complications during the
      pregnancy and delivery were also calculated. RESULTS: For the period of 10 years
      the teenage pregnancy rate was 5.10% /n= 594/5.10% of all 11657 deliveries
      /94.90%/. 504 of the patients were aged 35 to 39 years /4. 32%/ while only 90
      /0.78%/ were aged > 40 years old. In 54.88% of the cases the deliveries were not
      complicated; in the rest of the cases there were complications or the delivery
      ended surgicaly. CONCLUSIONS: The increasing frequency of the advanced age
      pregnancy and deliveries and improved pre and intranatal counseling has made
      advanced maternal age compatible with successful pregnancy for the great majority
      of such women.

PMID- 16637311
TI  - [Endoscopic treatment of ectopic pregnancy].
AB  - The authors show their own experience with endoscopic operative treatment of
      tubal pregnancy. They describe the different types of operative treatment.

PMID- 16637312
TI  - [Obesity and pregnancy].
AB  - The increasing frequency of preobesity and obesity in all age groups worldwide
      can be characterized as a pandemia. Obesity is a public health problem because it
      is a major contributing factor in the development of hypertension, heart disease,
      type II diabetes, osteoarthritis, respiratory problems and certain cancer. THE
      OBJECTIVE OF THE STUDY: To describe the prevalence of preobesity and obesity
      among pregnant women and to evaluate the impact of preobesity and obesity upon
      pregnancy and delivery. SUBJECTS AND METHODS: 255 women, aged between 17 and 39
      years old are conducted in the study. They have been admited to the Clinic of
      Obstetrics and Gynecology at the University Hospital "St. George" Plovdiv for the
      period of for months /January- April 2005/. The data of the patients are obtained
      from their history of the disease and the dokument of the newborn. BMI was
      calculated before and at the end of pregnancy. RESULTS: Preobesity and obesity
      are more frequent at more educated women, nuliparous women and women aged 30
      years and more. Obese women had a higher frequency of preeclampsia, gestational
      diabetes, macrosomia, and operative delivery. 33.33% (n=85) of the pregnant women
      start their pregnancy with abnormal weight or obesity. At the end of the
      pregnancy 72.94% (n=186) of them are in condition of preobesity and obesity.
      CONCLUSION: As overweight and obesity are associate with adverse pregnancy
      outcomes, the attention of the obstetritian must be directed to so called
      preconceptual consulting in order to limit the gaining of wight upon the optimal
      limit before and during pregnancy.

PMID- 16637313
TI  - [Hysteroresection of submucous myomas after treatment with zoladex].
AB  - The early and heavy clinical symptoms of the submucous myomas demand early
      surgical intervention. The new alternative to the classical abdominal operation
      is the transcervical hysteroresection which is miniinvasive and organ-preserving
      procedure. OBJECTIVE: to assess the effect of the preoperative treatment of the
      patients with Goserelin acetate (Zoladex) on the intraoperative measures
      (operation time, intraoperative complications, difficulty of the procedure).
      STUDY DESIGN: prospective. PATIENT(S) AND METHODS: Total of 50 women with
      submucous myomas underwent hysteroresection. Ten of them were treated with
      Zoladex for two months preoperatively. RESULTS: In the treated group a mean
      decrease of 10.16 mm of the myoma diameter was achieved. This is especially
      important for myomas above 30 mm in diameter because 10 mm decrease in diameter
      leads to significant reduction of the tissue volume which has to be resected. In
      the treated group the mean operation time was decreased by 17.08 min. and the
      operation was assessed as "easier" in 90% of the cases. The authors assessed that
      the positive effect of Zoladex consists not only of the decreasing of the myoma
      diameter but also of achieving an endometrial atrophy which significantly
      improves the conditions for performing the intrauterine operation. CONCLUSION:
      Hysteroscopic resection of submucous myomas after pretreatment with Zoladex is
      faster, easier and with less intraoperative complications.

PMID- 16637314
TI  - [Some new aspects of the treatment for cervical cancer of I B2 stage].
AB  - From 2000 till 2005 were retrospectively analyzed 150 cases with cervical cancer
      stage I B. All patients were operated by radical hysterectomy type I - III with
      lymph mode dyssection. In 120 patients the lymph modes were negative. 30 patients
      had GOG Score of > or = 120. The histology of 23 patients was squamous and for 7
      patients adenocarcinomas. All tumours were with invasion of outer third of the
      cervix. With exception of 2 patients all had lymph-vascular space invasion. In
      all 30 high risky patients with negative lymph nodes was used small field of
      postoperative radiation (dose 50-60 Gy). The patients were followed median for 40
      months, as we had only 2 patients with recurrence (6%). We did not have ileus,
      fistulas or any other complications. By resection of the bulky lymph nodes we
      converted the risky patients with macro metastases into patients with
      micrometastases. In the postoperative period we used small field of pelvic
      radiation. All this lead to less complications, less recurrences and better
      quality of life for these patients.

PMID- 16637315
TI  - [Expression of human papilloma virus (HPV) and P16ink4a in cervical
      intraepithelial neoplasia (CIN) and papilloma].
AB  - p16ink4a Is a tumor-supressor gene and a key regulator of the cell cycle. The
      neoplastic cervical epithelium (squamous and cylindric) intensely expresses the
      cyclin-dependent kinase inhibitor p16ink4a. It was shown that the expression of
      p16ink4a in the squamous cervical cancer was induced by HPV. The aim of our study
      was to reveal the frequency of expression of p16ink4a and of HPV in the different
      grades of CIN and in the papilomatous cervical lesions. We used biopsy material
      (n=11) and cone biopsies (n=10), collected from women with different grades of
      CIN and with papillomatous lesions, having different grades of koilocytotic
      dysplasia. The biopsy material, collected from one woman with squamous cervical
      cancer was also studied. Using the immunohistochemical procedure we determined
      the expression of p16ink4a and HPV in the changed squamous cervical epithelium.
      RESULTS: We found that the neoplastic epithelium in CIN II and CIN III intensely
      expressed p16ink4a. We observed positive immune reaction for HPV in only 22.7%
      from the cases with papillomatous lesions, having koilocytic dysplasia. In
      conclusion we can state that p16ink4a could be used as a marker for the exact
      determination of CIN lesions in the cervix uteri. The koilocytic dysplasia,
      determined histologically was not always HPV-positive.

PMID- 16637316
TI  - [Measurement of basal anti-Mullerian hormone level of healthy fertile women in
      Bulgaria].
AB  - OBJECTIVE: To establish mean and reference range of basal serum Anti-Mullerian
      hormona (AMH) levels in a group of healthy fertile Bulgarian women. METHODS: The
      present report covers the results of 9 month's period in which 72 healthy fertile
      Bulgarian women, aged 20-40 years were selected to determinate a reference group
      of healthy fertile women with normal values of AMH. Blood samples were collected
      on early follicular phase of menstrual cycle (2-4 days). AMH was analyzed in
      duplicate with the use of a double-antibody ELISA. RESULTS: We established mean
      values of AMH -1,46 +/- 0,93 in a group of healthy fertile Bulgarian women with
      mean 31,4 years of age. The values of AMH, which we obtained in the 10th
      percentile, 10th - 0,61 ng/ml and in the 90th percentile was 2.94 ng/ml.
      CONCLUSIONS: The measurement of AMH is a test easy for performance, with
      reference values for healthy fertile Bulgarian women -1,46 +/- 0,93 ng/ml.

PMID- 16637317
TI  - [Diagnostic possibilities of the flexible hysteroscopy in irregular uterine
      bleeding].
AB  - The aim of the present study was to evaluate the possibilities of diagnostic
      flexible hysteroscopy for women with irregular uterine bleeding. The study was
      based on 569 women aged between 26 and 72 years (mean age 46.78 years) with weak
      to moderate irregular uterine bleeding who had given agreement for invasive
      investigations. To all patients initially was performed diagnostic hysteroscopy
      with the help of a panoramic fibrohysteroscope Pentax LH-150 II (with 5 mm
      diameter), followed by classical endometrial curettage. The performed
      hysteroscopies found phase or other normal endometrium at 208 women (36.56%),
      hyperplasia and poliposis at 258 (45.34%), changes, suspected for atypia and
      neoplasia at 77 (13.53%) and other different findings at 26 women (4.57%). The
      following curettage showed the lack of adequate material from uterine cavity at
      24 women (4.2%). From the rest patients, at 466 (81.9%) the morphological
      findings were due to the dysfunctional reasons, other 51 (8.9%) were with
      different precancer and cancer lesions and at 28 cases, clinically and
      morphologically was found that the bleeding was due to the presence of sub mucous
      nodules, intrauterine devices, residua and pathology of the chorion. The
      comparison of the hysteroscopy results with the clinical and histological
      findings from the curettage of 454 women, showed good diagnostic possibilities
      (sensitivity of 78.4% and specificity of 92.5%) of the flexible hysteroscopy for
      evaluation of women with irregular uterine bleeding. This examination is
      relatively simple and save endoscopic technique, which require simultaneously
      performance of a direct biopsy, in order to improve its diagnostic accuracy.

PMID- 16637318
TI  - [Modern aspects of perioperative analgesia by using nonsteroidal anti
      inflammatory drugs in gynecology (Part I)].
AB  - It is an actual problem how to treat acute postoperative pain by using
      nonsteroidal anti-inflammatory drugs. Modern concepts for perioperative
      administration of these drugs are very important for the usual practice. The
      possibilities for optimal application of nonselective or selective COX-2
      inhibitors are examined in this review.

PMID- 16637319
TI  - [A rare case of a Mullerian tract anomaly].
AB  - A case of a Mullerian tract defect in a 26-years old patient is reported. The
      anomaly is detected during an undesired pregnancy. Diagnostic methods used in
      that case are described. Diagnostic difficulties in determining the type of the
      defect and classifying it according to AFS classification (1988) are discussed.
      The variety of Mullerian tract defects and necessity of individually designed
      plan for diagnosis and treatment of every particular patient are discussed.

PMID- 16637320
TI  - [Two cases of Hellp syndrome, clinics and therapy].

PMID- 16637321
TI  - [Pregnancy after treatment of primary sterility with zoladex in patient with
      essential thrombocytopenia].
AB  - We have a patient with essential /idiopathic/ thrombocitopeny and primary
      sterility, who becomes pregnant after medical and operative treatment. With the
      beginning of the menarche her menstrual cycle goes irregular with menstrual
      bleeding duration from 8 to 20 days, cystic ovaries, non-ovulation cycles,
      trombocytopeny and anemia. A laparotomy was performed twice, because of the
      existence of hemoperitoneum, caused by a rupture of the corpus luteum. After
      achieving a amenorrhoea with Zoladex treatment, a splenectomia was performed. As
      a result we observe a physiological recovery of the menstrual cycle, the
      ovulation cycle and the pregnancy. The patient's hematology and hemostaseology
      statuses went back to normal.

PMID- 16637322
TI  - [Mg2+ cation initiates the conversion of nucleoside triphosphate to nucleoside
      monophospate through a radical mechanism. Quantum molecular dynamics simulation].
AB  - DFT:B3LYP (6-311G** basis set) quantum molecular dynamics simulation was used to
      study the conversion of guanosine triphosphate (GTP) to guanosine monophosphate
      upon the action of Mg2+. The computations were carried out at 310 K in a basin of
      178 water molecules surrounding a Mg(2+)-GTP complex and imitating the behavior
      of the solvent. The cleavage of the Mg(2+)-GTP complex occurs over the 5-ps
      period and gives rise to two inorganic phosphates (Pi), a hydrated Mg2+ complex,
      atomic oxygen, and highly reactive GMP radical. The appearance of this radical is
      a result of action of the Mg2+ cation, which initiates the radical mechanism of
      GTP cleavage. At the very early step of interaction with GTP, Mg2+ is reduced to
      Mg+, thus producing an ion radical pair (+)Mg-GTP(3-). In the absence of Mg2+, a
      non-reactive form of GMP is formed rather than GMP; the process corresponds to
      hydrolytic cleavage of GTP through the ionic mechanism. The formation of GMP and
      its analogues with adenosine, cytidine, thymidine, and uridine is, seemingly, a
      key point in DNA and RNA synthesis.

PMID- 16637323
TI  - [On the fluorescence of bidistilled water after electrochemical treatment].
AB  - The short-wave fluorescence of bidistilled water treated in the cathode and anode
      chambers of two types of electrolysers made from different materials was
      investigated by fluorescence spectroscopy. It was shown that the electrochemical
      treatment of water did not induce intrinsic short-wave flyorescence of catholyte
      and anolyte in the case of quartz glass electrolyser. The increase observed in
      the intensity of intrinsic short-wavelength fluorescence of bidistilled water in
      the catholyte and anolyte of the electrolyser made from technical organic glass
      was caused by microcontaminations released from electrolyser material in the
      samples.

PMID- 16637324
TI  - [A probabilistic method for the calculation of energy of hydrophobic
      interactions].
AB  - A theoretical approach to the quantitative estimation of the energy of
      hydrophobic interactions on the molecular level has been developed. The model is
      based on the fundamental relationship between the probability of shaping of a
      cavity of the excluded volume in liquid water that results from fluctuations of
      density and free energy of prime hydrophobic solvates, hard spheres. This
      probability was estimated with the use of the probabilistic method in combination
      with experimentally observed data on density and radial distribution function of
      allocation. Free energy of hydrophobic interactions for a complex consisting of
      several hard spheres was determined. The critical value of the particles included
      in the complex was estimated.

PMID- 16637325
TI  - [Interaction between aromatic antibiotics and vitamins: 1H NMR analysis of the
      heteroassociation of nicotinamide and anthracycline antitumor antibiotics].
AB  - The interaction between anthracycline antitumor antibiotics daunomycin and
      novatrone and the vitamin nicotinamide has been investigated by one- and two
      dimensional 1H NMR spectroscopy (500 MHz). Due to significant differences in
      structures of the chromophores of interacting molecules, a two-site
      heteroassociation model has been developed, allowing the arrangement of one and
      two nicotinamide molecules on the chromophore of the antibiotic. The equilibrium
      association constant, thermodynamical parameters (deltaH, deltaS) of the
      heteroassociation of nicotinamide with daunomycin and novatrone and the induced
      proton chemical shifts in the heterocomplexes have been determined from the
      concentration and temperature dependences of proton chemical shifts of
      interacting molecules. The most favorable structures of 1:1 nicotinamide-
      daunomycin and nicotinamide-novatrone heteroassociation complexes have been
      determined using both the molecular mechanics methods (X-PLOR software) and the
      calculated values of induced proton chemical shifts. Analysis of the results
      obtained allows one to conclude that two nicotinamide molecules cannot
      simultaneously bind on one side of the chromophore of antibiotic. Heterocomplexes
      of the vitamin with the antibiotics with a stoichiometry 1:1 are mainly
      stabilized by the stacking of aromatic chromophores.

PMID- 16637326
TI  - [Functionalization of aminomodified probes for atomic force microscopy].
AB  - Probes for atomic force microscopy functionalized by bovine serum albumin were
      obtained, which may be used for molecular recognition studies. The procedure of
      the modification and functionalization of probes includes three stages. First,
      amino probes are obtained by modification in vapors of amino silane derivative.
      Then a homobifunctional amino reactive cross-linker is covalently linked to
      surface amino groups of the amino probe. And finally, the probe with the
      covalently attached cross-linker is functionalized by bovine serum albumin
      molecules. The probes obtained were characterized at different stages of the
      modification by atomic force microscopy: the adhesion force and the work of
      adhesion force were determined from histograms. The modification of probe surface
      was confirmed by visualization of bovine serum albumin and supercoiled pGEMEX DNA
      molecules immobilized on the amino mica and amino mica modified by cross-linker.

PMID- 16637327
TI  - [Measurement of specific surface energy of protein hydration shell using ESR of
      spin label].
AB  - An approach to determining the microscopic surface tension in water-protein
      matrix using EPR of spin label was developed. The approach in based on the use of
      viscosity isotherms of correlation time of spin labels bound to the protein
      macromolecule. Changes in specific surface tension of spin-labeled molecules of
      serum albumin, hemoglobin, and antibodies were studied depending on protein
      concentration, the structure of the reporter group, ligand state of the protein,
      and the presence of salts, water-soluble polymers, and D2O. Possible reasons of
      microscopic changes in surface tension are discussed.

PMID- 16637328
TI  - [Brownian dynamics simulation of the association of Bacillus amyloliquefaciens
      ribonuclease (barnase) and Bacillus intermedius ribonuclease (binase) with
      barstar].
AB  - A comparative study of the association of two ribonucleases, barnase and binase,
      with the polypeptide inhibitor barstar has been performed by the Brownian
      dynamics simulation method. It was shown that the method adequately reproduced
      the dependence of the association rate on pH and ionic strength of solution and
      the influence of mutations of some ribonuclease amino acids. Two types of
      energetically favorable complexes of binase-barstar encounter were determined. In
      the type I complex, the amino acids of binase active center take part in the
      complex formation. In the second complex, the active center is free. It was
      supposed that the temporary binding of barstar into complex of type II is
      competitive relative to the inhibition reaction. This can partially explain the
      decrease in the rate of binase inhibition as compared with the corresponding
      reaction of barnase.

PMID- 16637329
TI  - [Viscoelastic characteristics of protein solutions and micromechanics of their
      motion in porous carriers].
AB  - The interactions of model proteins with the templates of porous carriers in
      biosensors were analyzed in terms of events occurring during the molecular
      contact of biopolymers with a solid. The viscoelastic properties of casein and
      albumin at small widths of the layer of the solution applied to the crystal were
      estimated using the dynamic method of piezoqartz resonator. The experimental data
      on the viscoelastic characteristics of protein solutions of different
      concentrations were compared with the characteristics of their tangential motion
      in porous carriers from cellulose nitrate. It was found that the parameters of
      dynamic viscosity correlate with the time of motion of protein solution in a
      porous polymeric carrier.

PMID- 16637330
TI  - [The optical activity of the system cellulose acetate--mesophasogenic solvent in
      the formation of a lyotropic liquid-crystalline phase].
AB  - Vapors of a mesophasogenic solvent (which can form an liquid-crystalline phase
      with the polymer) have been found to actively affect the spatial structure and
      optical activity of natural polysaccharides (cellulose acetates). This process is
      accompanied by variations of the specific optical rotation value [alpha] within
      wide limits, including the inversion of the sign of [alpha]. The action of vapors
      obeys the dosage-effect rule, with lower doses producing a stronger effect. It
      was supposed that this approach can be applied to study the structural
      peculiarities of biopolymers such as DNA.

PMID- 16637331
TI  - [Effect of hydrogen bonds on the energetics of electron transfer].
AB  - For a model system consisting of a special pair of bacteriochlorophyll molecules
      (P) and a primary quinone with the nearest environment (QA) (which are acceptor
      and donor in the recombination reaction in Rhodobacter sphaeroides reaction
      center, respectively), energies of P+QA(-) and PQA states were calculated.
      Calculations were performed using several stable QA conformations differing by
      the positions of hydrogen bond protons. Essential influence of proton positions
      on the energy of vertical transition P+QA(-) --> PQA was shown.

PMID- 16637332
TI  - [The temperature factor and magnetic noise under the conditions of stochastic
      resonance of magnetosomes].
AB  - The influence of magnetic noise on the dynamics of magnetic nanoparticles under
      the conditions of stochastic resonance is considered. The effect of the magnetic
      noise is shown to be equivalent to the growth of the effective thermostat
      temperature for the particles at the permanent actual temperature of the medium.
      This regularity may be used for testing the hypothesis on the involvement of
      magnetic nanoparticles in the formation of biological effects of weak magnetic
      fields.

PMID- 16637333
TI  - [On measurements of higher harmonics of transmembrane current].
AB  - Measurements of higher harmonics of transmembrane current in bilayer lipid
      membranes from diphytanoyl phosphatidylcholine (DPhPC) in n-decane and n
      tetradecane, caused by alternating voltage applied to the membrane, have been
      conducted. A universal relation between the amplitudes of harmonics was suggested
      and experimentally checked. This allowed one to calculate the coefficients of
      expansion of membrane capacity in series with even powers of membrane voltage and
      to compare the inhomogeneity of membranes from diphytanoyl phosphatidylcholine in
      n-decane and n-tetradecane with respect to thickness.

PMID- 16637334
TI  - [Covalent binding of 1,N(6)-ethenoadenosine diphosphate to catalytic and
      noncatalytic sites of chloroplast ATP-synthase].
AB  - The catalytic and noncatalytic sites of the chloroplast coupling factor (CF1)
      were selectively modified by incubation with the dialdehyde derivative of the
      fluorescent adenosine diphosphate analogue 1,N(6)-ethenoadenosine diphosphate.
      The modified CF1 was reconstituted with EDTA-treated chloroplast thylakoid
      membranes. The influence of light-induced transmembrane proton gradient and of
      phosphate ions on the fluorescence of 1,N(6)-ethenoadenosine diphosphate
      covalently bound to catalytic sites of reconstituted CF1 (ATP-synthase) was
      studied. Upon illumination of thylakoid membranes with saturating white light,
      the quenching of fluorescence of covalently bound 1,N(6)-ethenoadenosine
      diphosphate was observed. The quenching was reversed by the addition of inorganic
      phosphate to the reaction mixture in the dark. Repeated illumination induced the
      quenching once again: however, the addition of phosphate ions did not affect the
      fluorescence intensity now. When 1,N(6)-ethenoadenosine diphosphate was
      covalently bound to noncatalytic sites of ATP-synthase, no similar fluorescent
      changes were observed. The interrelation of the observed changes of 1,N(6)
      ethenoadenosine diphosphate fluorescence and the mechanism of energy-dependent
      changes in the structure of the catalytic site of ATP-synthase is discussed.

PMID- 16637335
TI  - [Photodesorption of mitochondria].
AB  - A photodesorption of mitochondria absorbed on a quartz plate was found. The rate
      of desorption depends on the wavelength, and the intensity and time of
      irradiation. The maximal rate of photodesorption was detected upon ultraviolet
      irradiation at the absorption band of mitochondrial proteins. Probably, the
      photodesorption is caused by a local photothermal effect: a heating of
      photoexcited surface-membrane proteins, which attach mitochondria to the quartz
      plate. Preliminary fixation of a smear by isopropanol preserves the spontaneous
      desorption. No photodesorption of either mitohondria or formazan was observed
      upon irradiation of the smear with formazan by visible light (wavelength 540 nm;
      formazan was formed in the NADH-pNTV:reductase reaction). The data obtained are
      important for the elaboration of technology of mitochondrial immobilization in
      measurements of the enzyme activity and for biocensors.

PMID- 16637336
TI  - [Examination of chlorophyll fluorescence in sulfur-deprived cells of
      Chlamydomonas reinhardtii].
AB  - Modulated fluorometry (PAM) was applied for probing the photosynthesis in cells
      of C. reinhardtii during sulfur deprivation. A significant (up to a fourfold)
      increase in chlorophyll fluorescence yield (parameters F(o) and F(m)) normalized
      to chlorophyll concentration was shown for deprived cells. An analysis of
      nonphotochemical quenching of chlorophyll fluorescence indicated a considerable
      modification of the energy deactivation pathways in PS II of sulfur-deprived
      cells. Thus, starved cells exhibited a lower deltapH-dependent quenching of
      excited states and a higher thermal dissipation of excess light energy in
      reaction centers of PS II, as well as the transition of the photosynthetic
      apparatus primarily to state 2. However, these changes cannot cause the elevation
      of chlorophyll fluorescence in the cells under sulfur limitation. The phenomenon
      observed may be due to a partial dissociation of light-harvesting complexes from
      reaction centers of PS II and/or dysfunction of the dissipative cycle in PS II
      with cytochrome b559 as an intermediate.

PMID- 16637337
TI  - [Mechanism of action of biogenic chloramines and hypochlorite on initial
      aggregation of blood platelets].
AB  - The antiaggregant action of two reactive oxidants N,N-dichlorotaurine (chloramine
      of biogenic type) and sodium hypochlorite on the initial ADP-induced aggregation
      of rabbit blood platelets has been studied. Platelet aggregation in the
      reconstructed platelet-rich plasma (PRP) was measured by the nephelometric
      method, and the aggregation index was an increase in the intensity of small-angle
      light scattering. The introduction of chloramine at comparatively small
      concentrations (no greater than 1 mM active chlorine) directly into the
      reconstructed platelet-rich plasma induces the suppression of the initial
      aggregation (formation of small aggregates) several times stronger than in the
      case of its preliminary incubation with plasma alone. This suggests that N,N
      dichlorotaurine exerts its antiaggeregant action on the platelet-rich plasma by
      direct interaction with cells. The effects of the inhibition of platelet
      aggregation in two variants of introduction of high concentrations of N,N
      dichlorotaurine do not significantly differ. In this case a great amount of
      residual chloramine remains in the plasma, which just induces the suppression of
      platelet aggregation during subsequent reconstruction of the platelet-rich
      plasma. Similar data have been obtained in the study of the antiaggregant action
      of hypochlorite. N,N-Dichlorotaurine and hypochlorite at final concentrations of
      0.2-0.3 and 0.15 mM, respectively, inhibit strongly the initial aggregation of
      isolated platelets (approximately 2 x 10(8) cells in 1 ml) preliminarily
      activated for 1.5 min by the addition of 100-500 nM ADP. However, the
      antiaggregants show a more profound suppression of aggregation of unstimulated
      platelets. The antiaggregant effects of N,N-dichlorotaurine and hypochlorite are
      probably due to the oxidative modification of sulfur-containing groups in
      platelet plasmatic membrane.

PMID- 16637338
TI  - [Use of NMR spectroscopy in studies of sorbitol and glucose transformation by
      Gluconobacter oxydans].
AB  - NMR spectroscopy was applied for studying the products of glucose and sorbitol
      oxidation by cells of Gluconobacter oxydans. An analysis of 1H NMR spectra showed
      that the transformation of glucose results in the formation of diketogluconic
      acid, and sorbitol is oxidized to sorbose. In the 32P NMR spectra, only a signal
      of inorganic phosphate was detected, which accumulated in the medium as a result
      of cell lysis.

PMID- 16637339
TI  - [Differentiation of embryonic stem cells into cardiomyocytes with the help of
      cytokine LIF (leukemia inhibitory factor)].
AB  - An experimental model of differentiated mouse embryonic stem cells with
      retractive activity similar to that of cardiomyocytes without preliminary
      formation of embryoid bodies was obtained. The basic factor that induced in vitro
      embryonic cell differentiation into cardial type is the recombinant cytokine LIF
      under prolonged cultivation. The positive reaction of the cells with retractive
      activity to isoproterenol indicates the presence of the beta-adrenergic receptor
      activity characteristic only for terminal differentiated mammalian
      cardiomyocytes.

PMID- 16637340
TI  - [Influence of ionizing radiation on the condition of the protein-synthesizing
      system in ground squirrel brain neurons at different functional states].
AB  - It was shown by fluorescent and electron microscopy that the physiological state
      of ground squirrels subjected to ionizing radiation at different phases of the
      torpor-normothermia cycle plays a determining role in the alteration of the
      conditions of the protein-synthesizing system in neurons of hippocampus fields
      CA1 and CA3 and sensomotor area of the brain. In ground squirrels irradiated
      under normothermia, the neurons were less radioresistant and restored slower
      compared with torpor animal cells, the distinctions being most expressed in CA1
      field neurons. The effect of irradiation was minimum during the entrance into
      torpor and maximum during arousal. It was supposed that the inhibition of protein
      synthesis in the latter case occurred at the elongation stage when heavy
      polyribosomes were formed in neuron cytoplasm.

PMID- 16637341
TI  - [Influence of elongated refractoriness on forward masking of tone bursts in
      single units of the mouse inferior colliculus].
AB  - The responses of single units located in the inferior colliculus of albino mice
      narcotized by barbital were registered. Pairs of low-intensity tone bursts were
      used as stimuli. The probability of the response to the second burst in the pair
      was obtained under two conditions: the presence and absence of spike activity in
      the reaction to the first burst. With a 50-ms interval between the bursts in the
      majority of units, the probability of response was lower in the presence of spike
      activity in response to the first burst. In a few number of units, the opposite
      tendency was observed. As the interburst interval increased up to 100 and 200 ms,
      the dependence of the response probability to the second burst on the presence of
      the firing to the first one gradually weakened. The suppression of inhibitory
      inputs by bicuculline emphasized the effect of the afterspike decrease in
      excitability rather than weakened it. Possible mechanisms of interdependence of
      spike responses to two consecutive signals are discussed.

PMID- 16637342
TI  - [Comparison of the effects of laser and light-emitting diodes on lipid
      peroxidation in rat wound exudate].
AB  - The effect of laser and light-emitting diode radiation on lipid peroxidation in
      rat wound exudate was studied with the aim to compare the efficiency of coherent
      laser and incoherent light-emitting diode radiations. A model of aseptic wound in
      rat suggested by L.I. Slutskii was used. A He-Ne laser (632 nm) and a U-332B
      light-emitting diode were used in this study. The intensity of lipid peroxidation
      was estimated by the TBA assay. The antioxidative capacity of rat wound fluid was
      evaluated by means of chemiluminescent assays in two model systems: a) aqueous
      system with ABAP and luminol and b) in phospholipid liposome suspension with Fe2+
      and cumarin. It was shown that exposure of rat wounds to both laser and light
      emitting diode radiation decreased the concentration of TBA products and
      increased the antioxidative capacity of wound exudates, compared with the control
      group (without irradiation). The results obtained show that exposure of wounds to
      both laser and light-emitting diode irradiation causes a decrease in the
      oxidative stress in the rat wound fluid. No significant quantitative difference
      between the effects of laser and light-emitting diode irradiation was found.

PMID- 16637343
TI  - [The kinetic characteristics of lipids of animal tissues in autooxidation
      reactions].
AB  - The results of long-time research of antioxidative activity (AOA) of lipids from
      tissues of different species and lines of laboratory rodents are generalized. The
      classification of lipids according to their ability to inhibit the thermal
      autooxidation of methyl oleate is proposed. The participation of lipids in low
      temperature autooxidation reactions at the initiation and chain propagation
      stages was proved by means of the model proposed. In addition to the lipid
      antioxidative activity, the initial quantity of peroxides in lipids due to the
      extent of their unsaturation and lipid antiperoxide activity are proposed for the
      estimation of the kinetic characteristics of lipids. The dependence of effects on
      the rate of radical initiation in the system is shown to be caused by the
      influence of physicochemical properties of lipids on the interrelation
      coordination and balance of biochemical functions in biological objects differing
      in the intensity of oxidation processes.

PMID- 16637344
TI  - [Study of blood flow in microvessels using biospeckle dynamics].
AB  - The hydrodynamic properties of the blood plasma flow in smallest microvessels
      have been investigated. It has been shown that velocity distribution in such
      flows essentially differs from the Poseuille flow. The interrelations between the
      optical parameters and hydrodynamic characteristics of blood microflow have been
      analyzed. A new method for in vivo measurement of blood plasma rate in small
      microvessels is proposed, which uses in vivo microscopy in combination with
      speckle microscopy.

PMID- 16637345
TI  - [A model of heart ventricles for describing electrocardiograms in the estimation
      of the state of the myocardium].
AB  - A mathematical model of heart excitation processes for describing the
      electrocardiograms was developed. By using the model, it is possible to create a
      verified archive of model electrocardiograms and study the effect of individual
      variability of ventricle shape and the position of the heart in norm, in
      infarctions of different localization, and in ventricle hypertrophy. The
      consistency of real electrocardiograms with those obtained by computer-assisted
      modeling is discussed.

PMID- 16637346
TI  - [A conceptual model of the dynamics of the Syamozero lake community].
AB  - We have developed a conceptual mathematical model of the dynamics of a spatially
      heterogeneous population system, the prototype of which is the Syamozero lake
      fish community. Based on the analysis of solutions of the model, we show that
      interrelations between prey and predator populations in two neighboring habitats
      (pelagic and offshore zones) can lead to both undamped oscillations and
      stationary values of the population size. The population density was found to be
      close to the values oblained in the course of long-term observations of the biota
      of the Syamozero lake. Besides, we showed that the transition to the stationary
      states can be accompanied by long-term (dozens and hundreds of years) damped
      oscillations of the prey and predator population size. In natural waters, long
      term transition periods can prevent the attainment of stationary regimes of fish
      community functioning.

PMID- 16637347
TI  - [An experimental verification of the opponent theory of color vision of man].
AB  - An experimental study of colors observed by a human eye after a short flash of
      light of different spectral composition was carried out. Sequential images and
      changes in their color with time support the opponent theory of colored vision of
      man.

PMID- 16637348
TI  - [Cause-effect modeling as a general method of description and study of phenomena
      in complex hierarchical systems].
AB  - The definition of the cause-effect model of a phenomenon and the rules of
      presenting these models in the form of cause-effect diagrams have been
      formulated. The relationship between cause-effect modeling and traditional
      methods of mathematical modeling has been analyzed. Examples of cause-effect
      models (diagrams) of phenomena of different physical nature are given, and the
      application of these models in studies of some problems is demonstrated. In
      particular, the mechanism of renormalizing the rate constans of chemical
      reactions in terms of dissipative resonance is considered. In addition, the
      renormalization of the climate sensitivity parameters and the relaxation time of
      the Earth climate system in terms of the two-component (CO2 + H2O) greenhouse
      effect is considered.

PMID- 16637349
TI  - [On the periodicity in the fine structure of histograms during nuclear decay].
AB  - A possible explanation for the occurrence of periodicity in the fine structure of
      histograms during nuclear decay is proposed. The hypothesis states that, even in
      the absence of polarization, when the spin distribution of decaying nuclei over
      directions is, on the average, isotropic, the fine structure of histograms should
      depend, due to fluctuations, on the angles at which the sample is observed. There
      fore, when the Earth after some period would make a full furn, the distribution
      of fluctuations would return to the initial one, and, correspondingly, the fine
      structure of the histograms would repeat.

PMID- 16637350
TI  - Flying foxes cease to function as seed dispersers long before they become rare.
AB  - Rare species play limited ecological roles, but particular behavioral traits may
      predispose species to become functionally extinct before becoming rare. Flying
      foxes (Pteropodid fruit bats) are important dispersers of large seeds, but their
      effectiveness is hypothesized to depend on high population density that induces
      aggressive interactions. In a Pacific archipelago, we quantified the proportion
      of seeds that flying foxes dispersed beyond the fruiting canopy, across a range
      of sites that differed in flying fox abundance. We found the relationship between
      ecological function (seed dispersal) and flying fox abundance was nonlinear and
      consistent with the hypothesis. For most trees in sites below a threshold
      abundance of flying foxes, flying foxes dispersed < 1% of the seeds they handled.
      Above the threshold, dispersal away from trees increased to 58% as animal
      abundance approximately doubled. Hence, flying foxes may cease to be effective
      seed dispersers long before becoming rare. As many species' populations decline
      worldwide, identifying those with threshold relationships is an important
      precursor to preservation of ecologically effective densities.

PMID- 16637351
TI  - Species identity dominates the relationship between predator biodiversity and
      herbivore suppression.
AB  - Agricultural pest suppression is an important ecosystem service that may be
      threatened by the loss of predator diversity. This has stimulated interest in the
      relationship between predator biodiversity and biological control. Multiple
      predator studies have shown that predators may complement or interfere with one
      another, but few experiments have determined if the resulting effects on prey are
      caused by changes in predator abundance, identity, species richness, or some
      combination of these factors. We experimentally isolated the effect of predator
      species richness on the biological control of an important agricultural pest, the
      green peach aphid. We found no evidence that increasing predator species richness
      affects aphid biological control; overall there was no strong complementarity or
      interference among predator species that altered the strength of aphid
      suppression. Instead, our experiments revealed strong effects of predator species
      identity, because predators varied dramatically in their per capita consumption
      rates. Our results are consistent with other multiple-predator studies finding
      strong species-identity effects and suggest that, for the biological control of
      aphids, conservation strategies that directly target key species will be more
      effective than those targeting predator biodiversity more broadly.

PMID- 16637352
TI  - A resource-depletion model of forest insect outbreaks.
AB  - Detailed analyses of thresholded ecological interactions can improve our
      understanding of the transition from aperiodic to periodic dynamics. We develop a
      threshold model of the population dynamics of outbreaking bark beetle populations
      that alternate between non-epidemic and epidemic behavior. The model involves
      accumulation of resources during low-density periods and depletion during
      outbreaks. The transition between the two regimes is caused by disturbance events
      in the form of major tree felling by wind. The model is analyzed with particular
      reference to the population dynamics of the spruce bark beetle (Ips typographus)
      in Scandinavia for which a comprehensive literature allows full parameterization.
      The fairly constant outbreak lengths and the highly variable waiting time between
      outbreaks that are seen in the historical records of this species agree well with
      the predictions of the model. The thresholded resource-depletion dynamics result
      in substantial variation in the degree of periodicity between stochastic
      realizations. The completely aperiodic tree colonizations are partly predictable
      when the timing of the irregular windfall events are known. However, the
      predictability of inter-outbreak periods is low due to the large variation of
      cases falling most frequently in the middle between the extremes of purely
      nonperiodic (erratic) and periodic (cyclic) fluctuations.

PMID- 16637353
TI  - Defoliating insect immune defense interacts with induced plant defense during a
      population outbreak.
AB  - During population outbreaks, top-down and bottom-up factors are unable to control
      defoliator numbers. To our knowledge, details of biotic interactions leading to
      increased population density have not been studied during real population
      outbreaks. We experimentally assessed the strength of plant defenses and of
      insect immunocompetence, assumed to contribute to active insect resistance
      against parasitoids and pathogens, in the geometrid Epirrita autumnata during a
      steep increase in population density. We demonstrated rapid (same-season) induced
      resistance in the foliage of its host, mountain birch. The response was systemic,
      spreading throughout the tree, and retarded larval growth rate by approximately
      10%. On the other hand, no direct delayed carry-over effects were found in the
      next season in larval growth rate, mortality, or pupal mass. Larval damage to a
      tree during the previous year, however, significantly (by approximately 13%)
      accelerated the advance of the immune response (measured as melanization of an
      implant inserted into the pupal hemocoel). The encapsulation rate correlated
      positively with larval mortality in trees in which larvae had been introduced the
      previous year, but not in control trees. Both of these observations suggest that
      induced plant defense was associated with an increased insect immunocompetence
      during the population increase.

PMID- 16637354
TI  - Testing the irruptive paradigm of large-herbivore dynamics.
AB  - A dominant paradigm in understanding and managing large herbivores is that, after
      introduction to new range or release from harvesting, the herbivore population
      increases to peak abundance, crashes to a lower abundance, and then increases to
      a carrying capacity lower than peak abundance. However, support for the paradigm
      has been largely anecdotal. We first developed two mathematical models to better
      describe irruptive dynamics. The models differed in the form of the postcrash
      growth toward carrying capacity: the "Caughley model" included a time lag that
      generated dampening oscillations, and the "Leopold model" did not. We then
      evaluated which of four models (theta-logistic, delayed-logistic, Leopold, and
      Caughley) best described the dynamics of seven ungulate populations either
      introduced to new range (n = 5 populations) or released from harvesting (n = 2).
      The dynamics of six of the populations were best described by irruptive models
      (two by the Leopold, one by the Caughley, and three by the delayed-logistic), and
      one of the populations did not display irruptive dynamics (theta-logistic model).
      The limited data thus support the widespread existence of irruptive dynamics, and
      we encourage the consideration of irruptive models in studies of large-herbivore
      dynamics.

PMID- 16637355
TI  - The consequences of genetic diversity in competitive communities.
AB  - Several lines of evidence suggest that the species diversity and composition of
      communities should depend on genetic diversity within component species, but
      there has been very little effort to directly assess this possibility. Here I use
      models of competition among genotypes and species to demonstrate a strong
      positive effect of the number of genotypes per species on species diversity
      across a range of conditions. Genetic diversity allows species to respond to
      selection imposed by competition, resulting in both functional convergence and
      divergence among species depending on their initial niche positions. This ability
      to respond to selection promotes species coexistence and contributes to a
      reduction in variation in species composition among communities. These models
      suggest that whenever individual fitness depends on the degree of functional
      similarity between a focal individual and its competitors, genetic diversity
      should promote species coexistence; this prediction is consistent with the few
      relevant empirical data collected to date. The results point to the importance of
      considering the genetic origin and diversity of material used in ecological
      experiments and in restoration efforts, in addition to highlighting potentially
      important community consequences of the loss of genetic diversity in natural
      populations.

PMID- 16637356
TI  - Fish reintroductions reveal smooth transitions between lake community states.
AB  - Whether communities respond smoothly or discontinuously to changing environmental
      conditions has important consequences for the preservation and restoration of
      ecosystems. Theory shows that communities may exhibit a variety of responses to
      environmental change, including abrupt transitions due to the existence of
      alternate states. However, there have been few opportunities to look for such
      transitions in nature. Here, we examine the impact of a two-orders-of-magnitude
      decrease and then increase in planktivore abundance in Wintergreen lake
      (Michigan, USA), caused by the extinction and reintroduction of two dominant fish
      species (largemouth bass, Micropterus salmoides, and bluegill, Lepomis
      macrochirus). Over a 16 + yr period of slow change from high planktivory to low
      planktivory back to high planktivory, the zooplankton community changed smoothly
      and predictably between states. In years of low planktivory, the zooplankton
      assemblage was dominated by a single, large, cladoceran species, Daphnia
      pulicaria, whereas in years of high planktivory, D. pulicaria disappeared and was
      replaced by a suite of small-bodied cladocerans. We quantified the multivariate
      change in zooplankton community dissimilarity and found that community state
      smoothly tracked changes in planktivore density in both a forward and backward
      direction. Thus, there was little evidence of discontinuity in this system where
      transitions are strongly driven by planktivory.

PMID- 16637357
TI  - Density dependence in marine fish populations revealed at small and large spatial
      scales.
AB  - Experimental manipulation of population density has frequently been used to
      demonstrate demographic density dependence. However, such studies are usually
      small scale and typically provide evidence of spatial (within-generation) density
      dependence. It is often unclear whether small-scale, experimental tests of
      spatial density dependence will accurately describe temporal (between-generation)
      density dependence required for population regulation. Understanding the
      mechanisms generating density dependence may provide a link between spatial
      experiments and temporal regulation of populations. In this study, I manipulated
      the density of recently settled kelp rockfish (Sebastes atrovirens) in both the
      presence and absence of predators to test for density-dependent mortality and
      whether predation was the mechanism responsible. I also examined mortality of
      rockfish cohorts within kelp beds throughout central California to evaluate
      temporal (between-generation) density dependence in mortality. Experiments
      suggested that short-term behavioral responses of predators and/or a shortage of
      prey refuges caused spatial density dependence. Temporal density dependence in
      mortality was also detected at larger spatial scales for several species of
      rockfish. It is likely that short-term responses of predators generated both
      spatial and temporal density dependence in mortality. Spatial experiments that
      describe the causal mechanisms generating density dependence may therefore be
      valuable in describing temporal density dependence and population regulation.

PMID- 16637358
TI  - Testing isosource: stable isotope analysis of a tropical fishery with diverse
      organic matter sources.
AB  - We sampled consumers and organic matter sources (mangrove litter, freshwater
      swamp-forest litter, seagrasses, seagrass epiphytes, and marine particulate
      organic matter [MPOM]) from four estuaries on Kosrae, Federated States of
      Micronesia for stable isotope (sigma13C and sigma34S) analysis. Unique mixing
      solutions cannot be calculated in a dual-isotope, five-endmember scenario, so we
      tested IsoSource, a recently developed statistical procedure that calculates
      ranges in source contributions (i.e., minimum and maximum possible). Relatively
      high minimum contributions indicate significant sources, while low maxima
      indicate otherwise. Litter from the two forest types was isotopically
      distinguishable but had low average minimum contributions (0-8% for mangrove
      litter and 0% for swamp-forest litter among estuaries). Minimum contribution of
      MPOM was also low, averaging 0-13% among estuaries. Instead, local marine sources
      dominated contributions to consumers. Minimum contributions of seagrasses
      averaged 8-47% among estuaries (range 0-88% among species). Minimum contributions
      of seagrass epiphytes averaged 5-27% among estuaries (range 0-69% among species).
      IsoSource enabled inclusion of five organic matter sources in our dual-isotope
      analysis, ranking trophic importance as follows: seagrasses > seagrass epiphytes
      > MPOM > mangrove forest > freshwater swamp-forest. IsoSource is thus a useful
      step toward understanding which of multiple organic matter sources support food
      webs; more detailed work is necessary to identify unique solutions.

PMID- 16637359
TI  - Linking direct and indirect data on dispersal: isolation by slope in a headwater
      stream salamander.
AB  - There is growing recognition of the need to incorporate information on movement
      behavior in landscape-scale studies of dispersal. One way to do this is by using
      indirect indices of dispersal (e.g., genetic differentiation) to test predictions
      derived from direct data on movement behavior. Mark-recapture studies documented
      upstream-biased movement in the salamander Gyrinophilus porphyriticus
      (Plethodontidae). Based on this information, we hypothesized that gene flow in G.
      porphyriticus is affected by the slope of the stream. Specifically, because the
      energy required for upstream dispersal is positively related to slope, we
      predicted gene flow to be negatively related to change in elevation between
      sampling sites. Using amplified DNA fragment length polymorphisms among tissue
      samples from paired sites in nine streams in the Hubbard Brook Watershed, New
      Hampshire, USA, we found that genetic distances between downstream and upstream
      sites were positively related to change in elevation over standardized 1-km
      distances. This pattern of isolation by slope elucidates controls on population
      connectivity in stream networks and underscores the potential for specific
      behaviors to affect the genetic structure of species at the landscape scale. More
      broadly, our results show the value of combining direct data on movement behavior
      and indirect indices to assess patterns and consequences of dispersal in
      spatially complex ecosystems.

PMID- 16637360
TI  - Survival trade-offs between two predator-induced phenotypes in Pacific treefrogs
      (Pseudacris regilla).
AB  - In many organisms, specific predator species induce defensive phenotypes that are
      qualitatively different from the phenotypes induced by other predator species.
      This differential induction implies that there is no optimal phenotype that works
      best against all predators. However, few studies have actually tested the
      hypothesis that each predator-induced phenotype provides the highest survival
      rate in encounters with the predator that induced that phenotype. In this
      experiment, I reared Pacific treefrog (Pseudacris regilla) larvae with chemical
      cues from two different predators (bluegill sunfish and predaceous diving-beetle
      larvae), and without predator cues. The Pacific treefrog larvae in the three
      treatments differed in their morphology and foraging behavior. I then exposed
      tadpoles from each treatment to free-foraging predaceous diving beetles and
      bluegill sunfish. Tadpoles survived best when exposed to the predator whose cues
      they were reared with, and worst when exposed to the other predator. In both
      predator environments, the tadpoles reared in the nonpredator control treatment
      had intermediate survival between the two predator-induced groups. Thus, there is
      no generalized "antipredator" response to these predators; rather, there was a
      clear trade-off in survival abilities between the predators.

PMID- 16637361
TI  - Lethal and nonlethal predator effects on an herbivore guild mediated by system
      productivity.
AB  - Indirect effects propagated through intervening species in a food web have
      important effects on community properties. Traditionally, these indirect effects
      have been conceptualized as mediated through density changes of the intervening
      species, but it is becoming increasingly apparent that those mediated through
      trait (phenotypic) responses also can be very important. Because density- and
      trait-mediated indirect effects have different properties, it is critical that we
      understand the mechanisms of transmission in order to predict how they will
      interact, and when or where they will be important. In this study, we examined
      the mechanisms and consequences of the lethal (density-mediated) and nonlethal
      (trait-mediated) effects of a larval odonate predator on a guild of four
      herbivore species (a larval anuran and three species of snails) and their
      resources. We also manipulated system productivity in order to explore the
      effects of environmental context on the transmission of these two types of
      indirect effects. We show that trait-mediated effects arising from the predator
      can be very strong relative to density-mediated effects on both the competing
      herbivores and the species composition and production of their resources. A
      number of these indirect effects are shown to be contingent on productivity of
      the system. We further present evidence that trait- and density-mediated indirect
      effects originating from a predator may be transmitted independently through
      different routes in a food web, particularly when spatial responses of the
      transmitting prey are involved. Finally, effects on prey growth due to trait
      responses to the predator varied from negative to positive in predictable ways as
      a function of time and indirect effects on the larger food web. These results
      indicate the important role that trait-mediated indirect effects can play in
      trophic cascades and keystone predator interactions, and we discuss how the
      mechanisms involved can be incorporated in theory.

PMID- 16637362
TI  - The influence of size-specific indirect interactions in predator-prey systems.
AB  - Nonlethal indirect interactions between predators often lead to nonadditive
      effects of predator number on prey survival and growth. Previous studies have
      focused on systems with at least two different predator species and one prey
      species. However, most predators undergo extreme ontological changes in phenotype
      such that interactions between different-sized cohorts of a predator and its prey
      could lead to nonadditive effects in systems with only two species. This may be
      important since different-sized individuals of the same species can differ more
      in their ecology than similar-sized individuals of different species. This study
      examined trait-mediated indirect effects in a two-species system including a
      cannibalistic predator with different-sized cohorts and its prey. I tested for
      these effects using larvae of two stream salamanders, Gyrinophilus porphyriticus
      (predator) and Eurycea cirrigera (prey), by altering the densities and
      combinations of predator size classes in experimental streams. Results showed
      that the presence of large individuals can significantly reduce the impact of
      density changes of smaller conspecifics on prey survival through nonlethal means.
      In the absence of large conspecifics, an increase in the relative frequency of
      small predators significantly increased predation rates, thereby reducing prey
      survival. However, with large conspecifics present, increasing the density of
      small predators did not decrease prey survival, resulting in a 14.3% lower prey
      mortality than predicted from the independent effects of both predator size
      classes. Small predators changed their microhabitat use in the presence of larger
      conspecifics. Prey individuals reduced activity in response to large predators
      but did not respond to small predators. Both predators reduced prey growth. These
      results demonstrate that the impact of a predator can be significantly altered by
      two different types of trait-mediated indirect effects in two-species systems:
      between different-sized cohorts and between different cohorts and prey. This
      study demonstrates that predictions based on simple numerical changes that assume
      independent effects of different size classes or ignore size structure can be
      strongly misleading. We need to account for the size structure within predator
      populations in order to predict how changes in predator abundance will affect
      predator-prey dynamics.

PMID- 16637363
TI  - High survival in poor years: life history tactics adapted to mast seeding in the
      edible dormouse.
AB  - Edible dormice (Glis glis) reproduce in years with beech mast seeding, but entire
      populations may skip reproduction in years when tree seeds, a major food resource
      of this small hibernator, are absent. We tested the hypothesis that the year-to
      year variability in reproductive effort caused by this breeding strategy should
      lead to detectable differences in yearly survival rates. Therefore, we analyzed
      capture-recapture data from animals occupying nest boxes, collected over nine
      years at two study sites in Germany. Among fully grown adults (aged two years or
      older), survival probabilities were significantly lower (0.32 +/- 0.04) after
      reproductive years (n = 5) compared to years (n = 4) with absent or below-average
      reproduction (0.58 +/- 0.07) on both study sites. This trade-off between
      reproduction and subsequent survival was observed in both females and males and
      appears to be a relatively rare case in which costs of reproduction in terms of
      longevity are detectable at the population level. Effects of reproduction on
      survival were less pronounced when yearlings (with a generally lower reproductive
      effort) were included and were more distinct in a suboptimal habitat. Of those
      females breeding in nest boxes, 96.5% had only one or two litters within the
      study period. Considering these and previously published results, including a
      report of extremely high mean longevities (9-12 years) of dormice in a habitat
      with infrequent mast seeding, we conclude that edible dormice flexibly adjust
      life history tactics to local mast patterns. Long stretches of mast failures can
      in fact lead to relative semelparity, i.e., a strategy in which dormice "sit
      tight" for several years until environmental conditions are favorable for
      reproduction.

PMID- 16637364
TI  - Impact of parasite sympatry on the geographic mosaic of coevolution.
AB  - Slave-making ants are specialized social parasites that steal the young from
      colonies of their host species to augment their slave supply. The degree of
      parasite-host specialization has been shown to shape the trajectory along which
      parasites and hosts coevolve and is a prime contributor to the geographic mosaic
      of coevolution. However, virtually nothing is known about extrinsic influences on
      parasite-host dynamics, although the simple addition of a competing slave-maker
      may significantly alter selection pressures. Here we report the effect of two
      sympatric slave-makers on a single host. We measured temporal and spatial changes
      in colonies of the primary host Temnothorax curvispinosus that had been placed in
      field enclosures along with a single colony of either one or both species of the
      North American slave-making ants Protomognathus americanus and Temnothorax
      duloticus. Each slave-maker species alone had a negative impact on its hosts,
      although one slave-maker species more frequently decimated its host assemblage
      and then went extinct. Nevertheless, the combined effect in mixed-parasite
      enclosures was, surprisingly, greatly attenuated. Virulent slave-maker growth and
      prudent slave-maker decay in these shared enclosures, together with field data
      showing an inverse proportional relationship between the two slave-makers in
      natural populations, suggest that their checkered distribution is a consequence
      of direct asymmetrical antagonism between parasites. Thus, our results imply a
      tripartite coevolutionary arms race, whereby intraguild interactions among social
      parasites strongly affect the realized selection pressures on hosts and
      contribute to the geographic mosaic of coevolution.

PMID- 16637365
TI  - Fitness consequences of choosy oviposition for a time-limited butterfly.
AB  - For the majority of insects, a female's choice of oviposition site(s) greatly
      influences both the success of individual offspring and her own total fitness.
      Theory predicts that females most strongly limited by egg number will employ
      greater oviposition site discrimination than those predominately subject to time
      limitation. The reproductive success of the butterfly Pieris virginiensis at our
      Connecticut, USA, field site is strongly time constrained on two fronts. First,
      during their three-week flight season, only 60% of days and 28% of daytime hours
      were suitable for flight. Second, larval survival is impacted by the rapid
      senescence of their spring ephemeral host plant Dentaria diphylla, with eggs laid
      during the first half of the flight season having approximately three times the
      survival chance of those laid later. Yet, on average, females choose to oviposit
      on only half the plants they closely inspect and fly over most ramets without any
      inspection. Our experiments demonstrate that the preferred host ramets confer an
      approximate two-fold survival advantage. Females are not choosing plants that
      senesce later, despite the advantage that such plants would confer. We use
      empirical data on female behavior and larval performance to parameterize a
      simulation model. Model results suggest that, despite the notable time limitation
      in this system, the observed level of female oviposition site preference not only
      increases individual larval survival, but also total female fitness. Low egg
      loads in this species may contribute to selection for strong host plant
      discrimination.

PMID- 16637366
TI  - Predicting emergence, chorusing, and oviposition of periodical cicadas.
AB  - Periodical cicadas in the genus Magicicada have an unusual life history that
      includes an exceptionally long life cycle and a massive, synchronized emergence.
      Distributions in woodland habitat are extremely patchy, and an unresolved problem
      is how the patchiness is generated and maintained. We undertook a study in
      Princeton, New Jersey, USA, to determine if habitat factors such as tree height,
      distance to the nearest neighbor, and amount of foliage influence distributions
      of nymphal emergences, centers of chorusing aggregations, and oviposition sites.
      Emerging nymphs were counted, chorus centers were identified by measuring decibel
      levels of their songs, and oviposition was estimated from the foliage "flags"
      that are produced by trees in response to the damage caused by egg-laying. All
      three distributions were mapped on 50 trees in a human-managed area of 75 x 130
      m. We were unable to identify habitat features that were associated with the
      distribution of emergences, except that tulip trees (Liriodendron) had
      significantly fewer emergences than two other genera, ash (Fraxinus) and beech
      (Fagus). Using multiple linear regression analysis, we found that the
      distribution of emergences was the best predictor of the distribution of chorus
      centers and oviposition sites. In an analysis of ash trees alone, tree height and
      spacing, in addition to cicada emergences, predicted chorus centers and
      oviposition incidence. Thus the distribution of the offspring generation
      (oviposition) is shown to be similar to the parental generation (emergence). We
      suggest that their stability is maintained across generations by extremely low
      dispersal and mutual attraction. Aggregations may be thought of as self
      perpetuating, randomly distributed assemblages, initially established through the
      interaction of factors, including successful exploitation of underground
      resources, and avoidance of fungal disease and aboveground predation in the
      development of high-density mating aggregations.

PMID- 16637367
TI  - Invasive cordgrass modifies wetland trophic function.
AB  - Vascular plants strongly control belowground environments in most ecosystems.
      Invasion by vascular plants in coastal wetlands, and by cordgrasses (Spartina
      spp.) in particular, are increasing in incidence globally, with dramatic
      ecosystem-level consequences. We examined the trophic consequences of invasion by
      a Spartina hybrid (S. alterniflora x S. foliosa) in San Francisco Bay (USA) by
      documenting differences in biomass and trophic structure of benthic communities
      between sediments invaded by Spartina and uninvaded sediments. We found the
      invaded system shifted from an algae-based to a detritus-based food web. We then
      tested for a relationship between diet and tolerance to invasion, hypothesizing
      that species that consume Spartina detritus are more likely to inhabit invaded
      sediments than those that consume surface algae. Infaunal diets were initially
      examined with natural abundance stable isotope analyses and application of mixing
      models, but these yielded an ambiguous picture of food sources. Therefore, we
      conducted isotopic enrichment experiments by providing 15N-labeled Spartina
      detritus both on and below the sediment surface in areas that either contained
      Spartina or were unvegetated. Capitellid and nereid polychaetes, and
      oligochaetes, groups shown to persist following Spartina invasion of San
      Francisco Bay tidal flats, took up 15N from labeled native and invasive Spartina
      detritus. In contrast, we found that amphipods, bivalves, and other taxa less
      tolerant to invasion consumed primarily surficial algae, based on 13C enrichment
      experiments. Habitat (Spartina vs. unvegetated patches) and location of detritus
      (on or within sediments) did not affect 15N uptake from detritus. Our
      investigations support a "trophic shift" model for ecosystem response to wetland
      plant invasion and preview loss of key trophic support for fishes and migratory
      birds by shifting dominance to species not widely consumed by species at higher
      trophic levels.

PMID- 16637368
TI  - Extrinsic and intrinsic controls of zooplankton diversity in lakes.
AB  - Pelagic crustacean zooplankton were collected from 336 Norwegian lakes covering a
      wide range of latitude, altitude, lake area, mean depth, production (as
      chlorophyll a), and fish community structure. Mean zooplankton species richness
      during the ice-free season was generally low at high latitudes and altitudes.
      Further, lower species richness was recorded in western lakes, possibly
      reflecting constraints on migration and dispersal. However, despite obvious
      spatial limitations, geographic boundaries were only weak predictors of mean
      zooplankton richness. Similarly, lake surface area did not contribute positively
      to mean richness such as seen in other ecosystem surveys. Rather, intrinsic
      factors such as primary production and fish community (planktivore) structure
      were identified by regression analysis as the major predictors of zooplankton
      diversity, while a positive correlation was observed between species richness and
      total zooplankton biomass. However, in spite of a large number of variables
      included in this study, the predictive power of multiple regression models was
      modest (<50% variance explained), pointing to a major role for within-lake
      properties, as yet unidentified intrinsic forces, stochasticity, or dispersal as
      constraints on zooplankton diversity in these lakes.

PMID- 16637369
TI  - Feeding by larvae of intertidal invertebrates: assessing their position in
      pelagic food webs.
AB  - One of the leading determinants of the structure and dynamics of marine
      populations is the rate of arrival of new individuals to local sites. While
      physical transport processes play major roles in delivering larvae to the shore,
      these processes become most important after larvae have survived the perils of
      life in the plankton, where they usually suffer great mortality. The lack of
      information regarding larval feeding makes it difficult to assess the effects of
      food supply on larval survival, or the role larvae may play in nearshore food
      webs. Here, we examine the spectrum of food sizes and food types consumed by the
      larvae of two intertidal barnacle species and of the predatory gastropod
      Concholepas concholepas. We conducted replicated experiments in which larvae were
      exposed to the food size spectrum (phytoplankton, microprotozoan and autotrophic
      picoplankton) found in nearshore waters in central Chile. Results show that
      barnacle nauplii and gastropod veligers are omnivorous grazers, incorporating
      significant fractions of heterotrophs in their diets. In accordance with their
      feeding mechanisms and body size, barnacle nauplii were able to feed on
      autotrophic picoplankton (<5 microm) and did not consume the largest
      phytoplankton cells, which made the bulk of phytoplankton biomass in spring
      summer blooms. Balanoid nauplii exhibited higher ingestion rates than the smaller
      bodied chthamaloid larvae. Newly hatched C. concholepas larvae also consumed
      picoplankton cells, while competent larvae of this species ingested mostly the
      largest phytoplankton cells and heterotrophic protozoans. Results suggest that
      persistent changes in the structure of pelagic food webs can have important
      effects on the species-specific food availability for invertebrate larvae, which
      can result in large-scale differences in recruitment rates of a given species,
      and in the relative recruitment success of the different species that make up
      benthic communities.

PMID- 16637370
TI  - Biotic and abiotic regulation of lightning fire initiation in the mixedwood
      boreal forest.
AB  - Lightning fire is the dominant natural disturbance of the western mixedwood
      boreal forest of North America. We quantified the independent effects of weather
      and forest composition on lightning fire initiation (a detected and recorded fire
      start) patterns in Alberta, Canada, to demonstrate how these biotic and abiotic
      components contribute to ecosystem dynamics in the mixedwood boreal forest. We
      used logistic regression to describe variation in annual initiation occurrence
      among 10,000-ha landscape units (voxels) covering a 9 million-ha study region
      over 11 years. At a voxel scale, forest composition explained more variation in
      annual initiation than did weather indices. Initiations occurred more frequently
      in landscapes with more conifer fuels (Picea spp.), and less in aspen-dominated
      (Populus spp.) ones. Initiations were less frequent in landscapes that had
      recently burned. Variation in initiation was also influenced by joint weather
      lightning indices, but to a lesser degree. For each voxel, these indices
      quantified the number of days in the fire season when moisture levels were low
      and lightning was detected. Regional indices of fire weather severity explained
      substantial interannual variation of initiation, and the effect of forest
      composition was stronger in years with more severe fire weather. Our study is a
      conclusive demonstration of biotic and abiotic regulation of lightning fire
      initiation in the mixedwood boreal forest. The independent effects of forest
      composition emphasize that vegetation feedbacks strongly regulate disturbance
      dynamics in the region.

PMID- 16637371
TI  - Rain forest fragmentation and the proliferation of successional trees.
AB  - The effects of habitat fragmentation on diverse tropical tree communities are
      poorly understood. Over a 20-year period we monitored the density of 52 tree
      species in nine predominantly successional genera (Annona, Bellucia, Cecropia,
      Croton, Goupia, Jacaranda, Miconia, Pourouma, Vismia) in fragmented and
      continuous Amazonian forests. We also evaluated the relative importance of soil,
      topographic, forest dynamic, and landscape variables in explaining the abundance
      and species composition of successional trees. Data were collected within 66
      permanent 1-ha plots within a large (approximately 1000 km2) experimental
      landscape, with forest fragments ranging from 1 to 100 ha in area. Prior to
      forest fragmentation, successional trees were uncommon, typically comprising 2-3%
      of all trees (> or =10 cm diameter at breast height [1.3 m above the ground
      surface]) in each plot. Following fragmentation, the density and basal area of
      successional trees increased rapidly. By 13-17 years after fragmentation,
      successional trees had tripled in abundance in fragment and edge plots and
      constituted more than a quarter of all trees in some plots. Fragment age had
      strong, positive effects on the density and basal area of successional trees,
      with no indication of a plateau in these variables, suggesting that successional
      species could become even more abundant in fragments over time. Nonetheless, the
      52 species differed greatly in their responses to fragmentation and forest edges.
      Some disturbance-favoring pioneers (e.g., Cecropia sciadophylla, Vismia
      guianensis, V. amazonica, V. bemerguii, Miconia cf. crassinervia) increased by
      >1000% in density on edge plots, whereas over a third (19 of 52) of all species
      remained constant or declined in numbers. Species responses to fragmentation were
      effectively predicted by their median growth rate in nearby intact forest,
      suggesting that faster-growing species have a strong advantage in forest
      fragments. An ordination analysis revealed three main gradients in successional
      species composition across our study area. Species gradients were most strongly
      influenced by the standlevel rate of tree mortality on each plot and by the
      number of nearby forest edges. Species-composition also varied significantly
      among different cattle ranches, which differed in their surrounding matrices and
      disturbance histories. These same variables were also the best predictors of
      total successional-tree abundance and species richness. Successional-tree
      assemblages in fragment interior plots (>150 m from edge), which are subjected to
      fragment area effects but not edge effects, did not differ significantly from
      those in intact forest, indicating that area effects per se had little influence
      on successional trees. Soils and topography also had little discernable effect on
      these species. Collectively, our results indicate that successional-tree species
      proliferate rapidly in fragmented Amazonian forests, largely as a result of
      chronically elevated tree mortality near forest edges and possibly an increased
      seed rain from successional plants growing in nearby degraded habitats. The
      proliferation of fast-growing successional trees and correlated decline of old
      growth trees will have important effects on species composition, forest dynamics,
      carbon storage, and nutrient cycling in fragmented forests.

PMID- 16637372
TI  - Leaf structural diversity is related to hydraulic capacity in tropical rain
      forest trees.
AB  - The hydraulic resistance of the leaf (R1) is a major bottleneck in the whole
      plant water transport pathway and may thus be linked with the enormous variation
      in leaf structure and function among tropical rain forest trees. A previous study
      found that R1 varied by an order of magnitude across 10 tree species of
      Panamanian tropical lowland rain forest. Here, correlations were tested between
      R1 and 24 traits relating to leaf venation and mesophyll structure, and to gross
      leaf form. Across species, R1 was related to both venation architecture and
      mesophyll structure. R1 was positively related to the theoretical axial
      resistivity of the midrib, determined from xylem conduit numbers and dimensions,
      and R1 was negatively related to venation density in nine of 10 species. R1 was
      also negatively related to both palisade mesophyll thickness and to the ratio of
      palisade to spongy mesophyll. By contrast, numerous leaf traits were independent
      of R1, including area, shape, thickness, and density, demonstrating that leaves
      can be diverse in gross structure without intrinsic trade-offs in hydraulic
      capacity. Variation in both R1-linked and R1-independent traits related strongly
      to regeneration irradiance, indicating the potential importance of both types of
      traits in establishment ecology.

PMID- 16637373
TI  - Nutrient regulation of organic matter decomposition in a tropical rain forest.
AB  - Terrestrial biosphere-atmosphere CO2 exchange is dominated by tropical forests,
      so understanding how nutrient availability affects carbon (C) decomposition in
      these ecosystems is central to predicting the global C cycle's response to
      environmental change. In tropical rain forests, phosphorus (P) limitation of
      primary production and decomposition is believed to be widespread, but direct
      evidence is rare. We assessed the effects of nitrogen (N) and P fertilization on
      litter-layer organic matter decomposition in two neighboring tropical rain
      forests in southwest Costa Rica that are similar in most ways, but that differ in
      soil P availability. The sites contain 100-200 tree species per hectare and
      between species foliar nutrient content is variable. To control for this
      heterogeneity, we decomposed leaves collected from a widespread neotropical
      species, Brosimum utile. Mass loss during decomposition was rapid in both
      forests, with B. utile leaves losing >80% of their initial mass in <300 days.
      High organic matter solubility throughout decomposition combined with high
      rainfall support a model of litter-layer decomposition in these rain forests in
      which rapid mass loss in the litter layer is dominated by leaching of dissolved
      organic matter (DOM) rather than direct CO2 mineralization. While P fertilization
      did not significantly affect mass loss in the litter layer, it did stimulate P
      immobilization in decomposing material, leading to increased P content and a
      lower C:P ratio in soluble DOM. In turn, increased P content of leached DOM
      stimulated significant increases in microbial mineralization of DOM in P
      fertilized soil. These results show that, while nutrients may not affect mass
      loss during decomposition in nutrient-poor, wet ecosystems, they may ultimately
      regulate CO2 losses (and hence C storage) by limiting microbial mineralization of
      DOM leached from the litter layer to soil.

PMID- 16637374
TI  - A structural equation model to integrate changes in functional strategies during
      old-field succession.
AB  - From a functional perspective, changes in abundance, and ultimately species
      replacement, during succession are a consequence of integrated suites of traits
      conferring different relative ecological advantages as the environment changes
      over time. Here we use structural equations to model the interspecific
      relationships between these integrated functional traits using 34 herbaceous
      species from a Mediterranean old-field succession and thus quantify the notion of
      a plant strategy. We measured plant traits related to plant vegetative and
      reproductive size, leaf functioning, reproductive phenology, seed mass, and
      production on 15 individuals per species monitored during one growing season. The
      resulting structural equation model successfully accounts for the pattern of
      trait covariation during the first 45 years post-abandonment using just two
      forcing variables: time since site abandonment and seed mass; no association
      between time since field abandonment and seed mass was observed over these
      herbaceous stages of secondary succession. All other predicted traits values are
      determined by these two variables and the cause-effect linkage between them.
      Adding pre-reproductive vegetative mass as a third forcing variable noticeably
      increased the predictive power of the model. Increasing the time after
      abandonment favors species with increasing life span and pre-reproductive biomass
      and decreasing specific leaf area. Allometric coefficients relating vegetative
      and reproductive components of plant size were in accordance with allometry
      theory. The model confirmed the trade-off between seed mass and seed number.
      Maximum plant height and seed mass were major determinants of reproductive
      phenology. Our results show that beyond verbal conceptualization, plant
      ecological strategies can be quantified and modeled.

PMID- 16637375
TI  - Detecting an orientation component in animal paths when the preferred direction
      is individual-dependent.
AB  - An orientation component leads to directionally biased paths, with major
      consequences in animal population redistribution. Classical orientation analyses,
      which focus on the overall direction of motion, are useless for detecting such a
      component when the preferred direction is not common to the whole population, but
      differs from one path to another. In-depth path analyses are required in this
      case. They consist of determining whether paths are more suitably represented as
      biased or unbiased random walks. The answer is not easy because most animals'
      paths show some forward persistence propensity that acts as a purely local
      directional bias and, hence, blurs the possible occurrence of an additional,
      consistent bias in a preferred direction. I highlight the key differences between
      biased and unbiased random walks and the different ways orientation mechanisms
      can generate a consistent directional bias. I then examine the strength and
      weakness of the available methods likely to detect it. Finally, I introduce a new
      procedure based on the backward evolution of the beeline distance, from the end
      of the path, which might correspond to a goal toward which the animal orients
      itself, to each of the animal's preceding locations. This new procedure proves to
      be very efficient, as it requires only a small sample of short paths for
      detecting a possible orientation component.

PMID- 16637376
TI  - [Impact of pregestational obesity on nutritional state of pregnant women of
      Mexico City].
AB  - OBJECTIVE: To describe the impact of obesity on the nutritional status of Mexican
      pregnant women. PATIENTS AND METHOD: In a group of 155 pregnant women we assessed
      weight gain, nutrient intake before and during pregnancy, food patterns, and
      anemia prevalence. RESULTS: Weight gain in obese women during the third trimester
      was lower (2.2 kg) than in normal weight women (8.7 kg), and 22% of them lost
      weight. Obese women tend to consume less energy per kilogram of body weight. Some
      unhealthy food patterns were observed, including high saturated fat and
      cholesterol intake and low fruit and vegetable consumption. Anemia was present in
      28% of women. Some micronutrient deficiencies were observed (zinc, folate, iron
      and other vitamins). CONCLUSIONS: Studies to assess healthy weight gain among
      obese Mexican pregnant women are needed. Nutrition education should be done to
      promote healthy eating patterns in this population.

PMID- 16637377
TI  - [Oxitocin trough umbilical vein to shorten the third stage of labor].
AB  - OBJECTIVE: To examine the efficacy and safety of oxitocin administered through
      umbilical vein after delivery to diminish the incidence of retained placenta,
      blood loss and third stage of labour. METHODOLOGY: A double blind, clinical trial
      was performed in which 64 women in labour, any age, with normal pregnancies, with
      gestational time between 37 to 42 weeks, were randomized to one of two groups.
      Group 1 received 10 UI of oxitocin (2 mL) diluted in 18 mL of saline solution
      through umbilical vein, immediately after delivery. Group 2 received only 20 mL
      of saline solution. Blood loss, time of third stage of labour, retained placenta,
      nausea, vomit and arterial hypotension were measured. RESULTS: Blood loss was
      263.7 +/- 220.9 mL in group 1 (n=32) and 286.7 + 230.4 in group 2 (n=32) (p=0.68,
      Student T test). Time of third stage of labour was 265.3 +/- 383.9 seconds in
      group 1 and 197.1 +/- 314.3 in group 2 (p=0.44, Student T test). There was one
      retained placenta in group 1 and two in group 2 (RR 0.5 IC 0.04 a 5.24). There
      were not side effects in any group. CONCLUSIONS: Oxitocin trough umbilical vein
      immediately after delivery was not useful to diminish blood loss, retained
      placenta or time of third stage of labour.

PMID- 16637378
TI  - [Transient tachypnea of the newborn, obstetric and neonatal risk factors].
AB  - OBJECTIVE: To identify the obstetrics and neonatal risk factors associated with
      transient tachypnea of the newborn. PATIENTS AND METHODS: Case-control study of
      110 neonates with transient tachypnea and 110 newborns controls, between May and
      October 2000, in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca. The
      diagnosis of transient tachypnea was done by clinical and radiology data and
      exclusion of the other causes of respiratory distress. The exposure was
      documented by a direct interview to the mother and clinical information of the
      clinical expedient. The association was measured with the odds ratios and
      confidence interval of 95%. RESULTS: The frequency of transient tachypnea was of
      2 percent newborn alive. The risk factors that were associated with transient
      tachypnea was: low Apgar score at minute (OR: 33.74, CI 95%: 4.73-681.52),
      premature rupture of amniotic membranes (OR: 3.65, CI 95%: 1.53-8.90), cesarean
      section (OR: 2.01, CI 95%: 1.14-3.57) and masculine gender (OR: 2.02, CI 95%:
      1.14-3.60). It was more frequent in the cases the antecedent of diabetes mellitus
      and bronchial asthma. CONCLUSIONS: The results suggest that it's necessary to
      improve the obstetrics surveillance to diminish the frequency of low Apgar score
      and risk factors associated with transient tachypnea of the newborn.

PMID- 16637379
TI  - [Usefulness of office hysteroscopy].
AB  - OBJECTIVE: To demonstrate the efficacy and feasibility of the office hysteroscopy
      in the treatment of the endouterine pathologies. DESIGN: retrospective,
      descriptive and observational. PATIENTS AND METHOD: We included all the office
      hysteroscopies performed since February-2000 to August-2004 (n=84) in a private
      medical office. We performed 32 diagnostic procedures without anesthesia and 52
      operative procedures with anesthesia (I.V. sedation). We used a Karl Storz
      diagnostic telescope and a Bettocchi operative telescope. RESULTS: Postoperative
      care was in the office since 90 minutes and all patients went home without
      complications, Mean age of the patients was 38+/-10 years. The indications to
      perform the procedure were infertility and abnormal transvaginal bleeding. There
      were not complications. All of the diagnostic procedures were done without
      anesthesia and we verified patient satisfaction with a pain store since 1 to 10
      points. Twenty patients could get pregnant after the procedure and in two
      patients we detected endometrial carcinoma. CONCLUSION: With these results, we
      can assume that office hysteroscopy is a procedure with minimal complications
      when is performed by expert hands and with excellent patients' satisfaction and
      benefit.

PMID- 16637380
TI  - [Thermal balloon as a therapeutic choice in dysfunctional uterine bleeding].
AB  - OBJECTIVE: To demonstrate the results obtained with the use of the thermal
      balloon in the dysfunctional uterine bleeding treatment. PATIENTS AND METHOD: We
      studied 50 climacteric patients with dysfunctional uterine bleeding diagnosis.
      Those diagnosed with moderate to severe dysfunctional uterine bleeding (with
      hematic losses of 140 to 180 mL per event), without benign or malignant
      endometrial neoplastic compromise were selected for ablation. RESULTS: The
      immediate or mediate evolution was satisfactory: five patients had moderate to
      acute pain, and 20 of them had mild to moderate pain. Likewise, 10 patients had
      normal bleedings (60 to 80 mL), 8 hypooligomenorrhea (10 to 20 mL), and 7
      amenorrhea. CONCLUSIONS: Endometrial ablation with thermal balloon is an easy,
      useful, and important procedure in climacteric patients with excessive bleedings.

PMID- 16637381
TI  - [Natural history of breast cancer].
AB  - Breast women cancer is a disease with a lot of paradigms; then, it is a big
      problem of health. It is important to know its nature history, because breast
      cancer has a multifactor onset; therefore, we have to understand its behavior,
      since its risks factors, until patient's death by metastatic disease in the host.
      In this work we made a bibliography, analytic review that brings up concepts
      related since theirs sources, evolution, preclinical horizon, and clinical
      symptoms to the dead of host.

PMID- 16637382
TI  - [Pyometra as a complication of invasive endocervical cancer].
AB  - We present a case of pyometra due to cervical cancer in a 62 years-old female
      with purulent discharge, abdominal pain and vaginal bleeding. At the examination
      we found the cervix with a cupula form, an ulcer in the external orifice, and
      normal vaginal fornixes and parametria. During an attempt of edometrial biopsy we
      noticed the output of 150 mL of pus from the uterine cavity. The endocervical
      channel and orifice biopsy reported invasive epidermoid carcinoma, thus it was
      clinically classified as IBI. We began antibiotic treatment and asked for
      extension and preoperatory studies, which were normal. Three weeks after draining
      the purulent material we made radical hysterectomy. The histopathological report
      showed a moderately different epidermoid carcinoma, of two centimeters,
      endocervical, obstructive, and of 30 resected nodes; one of them had metastasis,
      for which it was sent to radiotherapy. Pyometra can be a complication of invasive
      endocervical cancer.

PMID- 16637383
TI  - [Radical panhisterectomy with pelvis lymphadectomy in the treatment of cervix
      cancer. 1951].

PMID- 16637384
TI  - [Increasing dominance of laparoscopic techniques in the surgery of the spleen in
      hematologic syndromes].
AB  - Parallel with the evolution of minimally invasive techniques more and more organs
      became the subject of different laparoscopic operations. The spleen was not an
      exception to this trend, the first laparoscopic splenectomy was performed in
      1991. In the present publication the authors give an overview of their own
      initial experience with the technique. Between the time period of January 1996
      and April 2005, 204 splenectomies were carried out at the 1st Dept. of Surgery,
      University of Debrecen. The indication was haematological in 113 cases, the
      choice of operation was laparoscopic splenectomy in 18 cases. The male-female
      ratio was 7 to 11, the mean age was 45.6 years (21-71). The average operation
      time lasted 106 minutes (60-200 min.), the mean hospital stay was 11.9 days (5-50
      days). Laparoscopy had to be converted to open procedure in three cases, because
      of bleeding and adhesions. In one case, laparoscopic reoperation was necessary
      with the indication of subphrenic haematoma on the fifth postoperative day. One
      death occurred in this series from bilateral pneumonia. The authors conclude that
      laparoscopic splenectomy can be carried out safely, blood loss is limited, and
      the widely recognized advantages of laparoscopic techniques can be secured for
      the patients.

PMID- 16637385
TI  - [Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous
      neoplasms (IPMN)].
AB  - Pancreatic Intraepithelial Neoplasia (PanIN1-3) and Intraductal Papillary
      Mucinous Neoplasms (IPMNs) putative precursors of and associated to pancreatic
      cancer represent a distinct, however pathologically heterogenous entity. Recently
      a new classification and nomenclature was established. We analysed the
      clinicopathologic and cytogenetic characteristics of six patients with PanIN and
      two with IPMN undergoing curative surgical resection. The most valuable tool in
      the diagnosis of these preinvasive neoplasms is ERCP combined with brush
      cytology. Conventional laboratory blood tests, tumor markers (CEA, CA19-9) were
      within normal values and imaging modalities were informative in only one third of
      the cases, however, not pathognostic. Based on our hypothesis that tumor ploidy
      pattern correlates with biological behaviour, malignant potential and prognosis,
      we measured the nuclear DNA content, ploidy, synthetic (S) phase or proliferative
      fractions of each neoplasm by flow cytometry. Each neoplasm demonstrated diploid
      stemline, with a low mean S-phase or proliferative fraction (3,77%) and mean DNA
      index (DI) of 0.96. The diploid DNA pattern and the low proliferative activity
      are consistent with the nonaggressive biological behavior of intraepithelial and
      intraductal neoplasms and, in part, explain their favorable prognosis.

PMID- 16637386
TI  - [Predictive factors in esophageal cancer after neoadjuvant therapy].
AB  - BACKGROUND: Preoperative chemoradiation therapy (PCX) was introduced to improve
      the outcome of patients with oesophageal cancer (EC), but conflicting results
      have been released. Some 20-30% of patients show a complete pathological
      response, however, the perioperative morbidity and mortality is increased. To
      search for factors indicating response prior to the onset of PCX we investigated
      the proliferative activity (MIB-1), the expression of vascular endothelial growth
      factor (VEGF), and the capillary density (CD34) tissue specimens of ECs were
      available by endoscopy prior to the start of the treatment. METHODS: Forty-six
      (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56
      patients undergoing pretherapeutic endoscopy, PCX and surgery. Perioperative
      morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF
      and CD34 expression were investigated immunohistochemically. Multivariate
      analysis was carried out to prove independence of investigated variables.
      RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patents. Eight
      of 56 patients who received PCX died in hospital. Survival was significantly
      different between the group of complete responders (n=14) and non-responders
      (n=23; P = 0.0026). None of investigated tumour samples from patients with a
      complete response (CR) had a proliferation index of less than 45. Tumour samples
      from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of
      tumours with no response (P = 0.035). CD34 expression showed a correlation with
      VEGF expression. The relation of mean indices of VEGF expression and
      proliferative activity in tumours from patients with complete, partial or no
      response was 10. 7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS:
      According to these results, it may be expected that tumours with a VEGF/MIB-1
      ratio of 1:5 or less prior to PCX will respond to this therapy.

PMID- 16637387
TI  - [Peritonectomy and intraperitoneal chemotherapy in the treatment of peritoneal
      carcinosis].
AB  - The surgery of metastatic gastrointestinal malignancies comes into prominence
      nowadays. Positive observations inspire the increase of surgical radicality.
      Occurrence of peritoneal carcinosis means a very bad prognosis. However, on the
      base of the literature and our experiences the prognosis can be improved in some
      well-defined groups of patients. We present the method and opportunity of using
      peritonectomy and intraperitoneal chemotherapy in connection with two cases. We
      review the method developed and improved by Sugarbaker and his workgroup. Good
      results can be achieved by this combined technique in the cases of less invasive
      tumours, for example pseudomyxoma peritonei and peritoneal mesothelioma. Good
      result can also be achieved in the cases of more aggressive tumours if they are
      in resectable stage with not so extensive peritoneal seeding. Surveying the
      literature we can find encouraging results concerning ovarian cancer, gastric and
      colo-rectal cancer accompanied by peritoneal seeding.

PMID- 16637388
TI  - Rare incidence of pulmonary gangrene--algorithm of the treatment.
AB  - The pulmonary gangrene is rare and serious disease. Our experience is based on
      the treatment of the 2 patients with pulmonary gangrene during the last twenty
      years. The first and lifesaving step in the treatment of sepsis is the early
      removal of the necrotic tissue. Next surgery succeeds usually after one week
      after initial treatment. Surgical treatment continues step by step, we do not
      advise providing of a major anatomical resection in the initial stage of the
      disease. This policy is effective in the treatment of this serious disease.

PMID- 16637389
TI  - [Laparoscopic extirpation of retroperitoneal bronchogenic cyst].
AB  - The retroperitoneal bronchogenic cyst is an extremely rare anomaly. During the
      examination of an 18-year-old female patient due to her extreme thinness, the
      abdominal ultrasound and later the CT indicated as an accidental finding--a left
      side adrenal/suprarenal adenoma, which turned out to be hormonally inactive. But
      while we were doing a laparoscopic surgical intervention we found a 6-8-cm cyst
      in the retroperitoneum, between the greater curvature and the spleen. It
      contained light grey, mucinous liquid. The left suprarenal gland had normal size
      and appearance. During the microscopic examination the removed terime showed
      cystic structures, which were covered inside with multilayer ciliated columnar
      epithelium, mucous excretory glands, a whole layer of connective/interstitial and
      smooth muscle tissue. Neither cartilage, nor gastrointestinal epithelium was
      found. Only a few publications have reported about retroperitoneal bronchogenic
      cyst so far. These lesions occur very rarely at the greater curvature. Although
      this alteration is really unusual, bronchogenic cysts have to be expected in the
      differential diagnostics of the retroperitoneal tumors.

PMID- 16637390
TI  - [Pneumatosis cystoides intestinalis].
AB  - Authors present a case history of pneumatosis cystoides intestinalis with free
      intraperitoneal gas mimicking abdominal hollow organ perforation. The illness
      occurred in old immunocompromised man. The diagnosis was based on exploratory
      laparotomy and supported by abdominal x-ray and ultrasound.

PMID- 16637391
TI  - [Laparoscopic devascularization of the stomach and the abdominal esophagus with
      the LigaSure instrument in a porcine model].
AB  - OBJECTIVES: In this study we proved the feasibility of a new minimally invasive
      procedure for the devascularisation of the proximal stomach and the abdominal
      esophagus to prevent recurrent variceal bleeding in portal hypertension in a new
      animal model. MATERIALS AND METHODS: Experiments were performed on 12 female
      pigs, in two animal groups. In the first step (I. group n=6) portal hypertension
      was created by controlled laparoscopic clip ligation of the portal vein. The
      increased portal pressure was established by the needle puncture of the portal
      vein and the spleen. Two weeks later, the dilated veins were sealed along the
      lesser and greater curvature and the transhiatal esophagus with the 10 mm
      LigaSure instrument. Successful of the experimental model had encouraged us to
      perform this method on other animals (II. group, n=6), using the 5 mm instrument.
      RESULTS: There was no intraoperative bleeding after using both LigaSure
      instruments. Autopsy (2 weeks later) showed correct placed clips with partial
      occlusion of the portal vein without portal vein thrombosis. There was no
      evidence of postoperative bleeding. Histological investigation of the gastric
      surface confirmed complete sealing of the extended varices. CONCLUSION: The
      laparoscopic LigaSure instrument was found to be safe and suitable equipment for
      the ligation of the dilated veins along the gastric surface and the abdominal
      esophagus, and this method could be an alternate choice for the patients with
      recurrent variceal bleeding.

PMID- 16637392
TI  - [Oxidative stress and leukocyte activation after lower limb revascularization
      surgery].
AB  - The authors aimed to study of oxidative stress and thrombocyte function in the
      perioperative interval following the revascularization surgery of lower limb. The
      prospective randomised study involved 10 patients whose surgical interventions
      were indicated by lower limb embolism, thrombosis or abdominal aorta aneurysm,
      and 10 healthy volunteers were also involved in the study. Peripheral blood
      samples were collected before, and after the surgery (2, 24 hours and one week).
      The maximal free radical production and lag time of the free radical production
      of activated leukocytes were measured, and leukocyte adhesion molecules (CD11a
      and CD18) signing leucocyte activation were determined as well. Endogenous
      antioxidant defence status, reduced glutathione (GSH), total thiol-groups (-SH),
      SOD activity and thrombocyte function were investigated in platelet rich plasma
      and in whole blood. White blood cell count and free radical production was
      significantly higher in patients group before surgery than in healthy group (in
      case of the free radical production the difference proved to be 10 times (p <
      0.01)) and elevated continuously during the observation time. The CD11a and CD18
      expression of the granulocytes significantly decreased right after the
      revascularization, but with a gradual elevation, until the 7th day they exceed
      the ischaemic value. GSH concentration decreased significantly 2 and 24 hours
      after surgery and total thiol groups (-SH) followed the same kinetics. SOD
      activity was significantly lower in patients group haemolysates before surgery
      when it was measured in healthy groups (p < 0.01) and decreased further
      significantly 24 hours after the surgery (p < 0.01 vs. before surgery).
      Suppressed thrombocyte aggregation was detected in platelet rich plasma and in
      whole blood during the observation excepted the one week samples, where a highly
      significant elevation in ADP and collagen induced aggregation were observed. Our
      results show a great alteration in the antioxidant-prooxidant balance and the
      insufficiency of platelet aggregation's inhibition after peripheral vessel
      closure and revascularization intervention. We suggest the monitoring of the
      antioxidant status and thrombocyte function of patients going to underwent
      surgical intervention and if it necessary the therapeutic help.

PMID- 16637393
TI  - [To the Editor: Regarding "Current possibilities in the treatment of infected
      pancreatic necrosis"].

PMID- 16637394
TI  - Yaws and its eradication in India--a brief review.
AB  - Until 1996-97, when Yaws Eradication Programme (YEP) in India was launched, there
      were three initiatives to assess/control the yaws disease in the country. YEP was
      initially started as pilot study in Koraput district, Orissa and later on
      extended to ten states covering 49 districts. The first goal has been to get the
      disease eliminated from the country with ultimate goal being its eradication.
      Strategies for YEP are active case detection and treatment including contacts and
      targeted IEC. The number of reported cases reduced from 735 in 1997 to "Zero
      Case" in 2004 from entire country. The recent Third Independent Appraisal of YEP
      could not confirm any new yaws case. However, before declaring the elimination
      (meaning no new early infectious case), there is need to make a thorough search
      in the affected areas. Future activities under the programme includes sero-
      surveillance among under-five children to demonstrate cessation of yaws
      transmission.

PMID- 16637395
TI  - Tolerability and efficacy of a three-age class dosage schedule of
      Diethylcarbamazine citrate (DEC) in the treatment of microfilaria carriers of
      Wuchereria bancrofti and its implications in mass drug administration (MDA)
      strategy for elimination of lymphatic filariasis (LF).
AB  - A six-age class dosage schedule of Diethylcarbamazine (DEC) of 50mg (1-2 years),
      100mg (3-4 years), 150mg (5-8 years), 200mg (9-11 years), 250mg (12-14 years) and
      300mg for above 14 years is being adopted for annual single dose MDA for LF
      elimination treat Wuchereria bancrofti microfilaria carriers. In order to
      increase the community compliance as well as to make the distribution easier
      during MDA, a revised 3 age class dosage schedule of 100mg (2-4 years), 200mg (5
      14 years) and 300mg for above 14 years was evaluated for its tolerability and
      efficacy. By this change, it was observed that the 4-8 years age class is
      receiving 50 mg higher and 11-14 years age class is receiving 50mg lesser dose
      compared to the earlier class schedule. Therefore, the safety aspect in the age
      class of 4-8 years and efficacy component in the age class of 11-14 years were
      assessed. Apparently "healthy" asymptomatic microfilaraemic volunteers between
      the age class of 4-8 and 11-14 years were recruited for the study. The incidence
      of side reaction in the 4-8 years age class was 50.0% with 150mg dose and 66.7%
      with 200mg (P>0.05). No life threatening adverse reactions was observed in any
      dosage schedule. Fever, headache and myalgia, the predominant adverse reactions
      were mild and similar in both schedules. The mean intensity of the three major
      specific adverse reactions (fever, headache and myalgia) also did not differ
      significantly (P>0.05). For the purpose of LF elimination, efficacy in terms of
      reduction in mean microfilaria load is important. In the 11-14 year age class
      considerable reduction in the geometric mean density (GMD) was observed by day 90
      and 180 post-therapy in both groups (250mg group and 200mg group) compared to pre
      therapy level. By day 360 post-therapy, the difference was statistically not
      significant (P>0.05) (reduction of 72.2% in 250mg and 69.6% reduction in 200mg).
      The reductions in GMD were statistically significant when compared to pre-therapy
      levels in both the old (250mg) and new (200mg) doses. Thus, three- age class
      dosage schedule is as safe and efficacious as the six- age class schedule.

PMID- 16637396
TI  - Bacteriophage in the treatment of experimental septicemic mice from a clinical
      isolate of multidrug resistant Klebsiella pneumoniae.
AB  - Drug resistance is the major cause of increase in morbidity and mortality in
      neonates. The emergence of antibiotic-resistant bacterial strains requires the
      exploration of alternative antibacterial therapies and the concern that human
      kind in re-entering the 'pre-antibiotic era' has become very real and the
      development of alternative anti-infection modalities has become one of the
      highest priorities of modern medicine and biotechnology. This has spurred
      biomedical researchers to expand their efforts to identify new technologies and
      products that employ novel mechanism of action against the "super-bugs". One of
      such alternatives stems up from an old idea is the bacteriophage therapy, which
      led our group to study the ability of bacterial viruses (bacteriophages or
      phages) to rescue septicemic mice with multidrug resistant (MDR) Klebsiella
      pneumoniae isolated from neonatal septicemia. The phage strain used in this study
      had lytic activity against a wide range of clinical isolates of MDR Klebsiella
      pneumoniae. One of these MDR Klebsiella strain was used to induce septicemia in
      mice by intraperitoneal (i.p.) injection of 10(9) CFU. The resulting bacteremia
      was fatal within 48 h. A single i.p. injection of 3x10(8) PFU of the phage strain
      administered 45 min after the bacterial challenge, was sufficient to rescue 100%
      of the animals. Even when treatment was delayed to the point where all animals
      were moribund, approximately 50% of them were rescued by a single injection of
      this phage preparation. The ability of this phage to rescue septicemic mice was
      demonstrated to be due to the functional capabilities of the phage and not to a
      nonspecific immune effect. The rescue of septicemic mice could be affected only
      by phage strains able to grow in vitro on the bacterial host used to infect the
      animals and when such strains are heat inactivated they lose their ability to
      rescue the infected mice.

PMID- 16637397
TI  - Characterization of Acinetobacter from clinical isolates at Gandhi memorial and
      associated hospitals, Lucknow.
AB  - The study was conducted in 4140 clinical samples sent to Microbiology department
      from different department of G.M. and associated hospitals. The samples included
      2270 urine, 960 pus, 300 blood, 210 sputum, 180 CSF, 20 intercostal drainage
      tubes and 150 other swabs like vaginal and urethral, conjunctival smear 30, 10
      ascitic fluids and 10 gastric aspirates. Apart from this, 30 specimens were
      collected from hospitals environment, like linen and trolley. From clinical
      samples, 43 acinetobacter strains (1.04%) were isolated. 17 strains (0.41%), were
      from pus, 12 (0.28%), from respiratory tract, 1, was (0.02%) from intercostal
      drainage secretions, urine 9 (0.22%), blood 1 (0.2%) and CSF 3 (.72%). From
      environmental samples, 7 strains (23.33%) were isolated. All the isolated strains
      were identified by routine biochemical tests. They were preserved in 1 % agar
      media for characterization. Characterization was done on the basis of growth at
      37 degrees c, 41 degrees c and 44 degrees c, hemolysis, gelatin hydrolysis, acid
      from glucose, utilization of citrate, L-phenyl alanine, malonate, B-alanine, L
      arginine, L-ornithine and L-aspartate. Among species identified Acinetobacter
      baumannii was 30 (69.67%), from clinical specimens and 5 (71.42%) from
      environment, Acinetobacter lwoffi was 10 (23.25%) from clinical specimen and 2
      from environmental specimen, Acinetobacter hemolyticus was 3 (6.97%) and none
      from the environment. All the strains were resistant to penicillin. The
      sensitivity pattern showed gentamycin 64% sensitive, cotrimaxazole 42% cefotoxin
      32% ciprofloxacine 26% and tetracycline 16%.

PMID- 16637398
TI  - Morphological variations in Phlebotomus argentipes (Diptera: Psychodidae)
      Annandale and Brunetti.
AB  - Morphological variations were observed in Phlebotomus argentipes, the vector for
      visceral leishmaniasis reported from the endemic states of Bihar, West Bengal and
      Uttar Pradesh. The taxonomic features distinguishing vector and nonvector species
      of P. argentipes were relative length of ascoid and antennal segment IV. Three
      morphotypes were characterized as <0.4, = 0.4 and >0.4 respectively. Other
      characteristics of wing width, wing length, eye, style, antennal segment III, IV,
      V was found statistically significant (p<0.05) and eleven other morphological
      measurements were not significant. This study suggests three different
      morphotypes of P. argentipes in these three endemic states. The genetic and
      reproductive isolation among such morphotypes will establish the variability in
      further studies.

PMID- 16637399
TI  - Geographical information system (GIS) in investigation of an outbreak.
AB  - An outbreak of fever in a village in southern India was reported on 1st
      September, 2001. The first reported case presented with epistaxis and a platelet
      count of 27000h(1)/mm3. Clinical, laboratory and entomological evidence supported
      a diagnosis of dengue fever. One third of the village was affected and 3.7 % of
      the population presented with haemorrhagic symptoms; none were fatal. Five acute
      cases tested for dengue specific IgM showed that two were positive. The larvae of
      Aedes aegypti were discovered from domestic water collections in the village.
      Spatial analysis done with the help of Geographical Information Systems software
      (GIS) demonstrated a centrifugal spread of cases from the most affected street
      until it involved the entire village. Spatial analysis revealed that cases
      occurred in clusters and that these could not have occurred by chance. This was
      our first experience in producing a geo-referenced map of a village area and in
      spatial analysis. GIS is a novel and simple tool for outbreak investigations and
      the spatial analyst adds additional information to the data collected. Control of
      adult mosquitoes and larvae prevented the outbreak from spreading to an adjacent
      village.

PMID- 16637400
TI  - Studies on drug metabolizing enzymes during arteether treatment of Plasmodium
      yoelii nigeriensis infected mice cerebral microvessels.
AB  - Human cerebral malaria is caused by a protozoan parasitic with no cure till date.
      The isolation of brain capillaries i.e. microvessels has permitted the in vitro
      study related to cerebral function. Microvessels were isolated from normal and P.
      yoelii infected mice brain cortex and subjected to biochemical characterization
      by the following enzyme markers viz alkaline phosphatase, gamma-glutamyI
      transpeptidase and monoamine oxidase and electron microscopically. Limited
      studies have been carried out in relation to drug metabolizing enzymes in
      cerebral microvessels of rodents. The present studies have been carried out in
      relation to status of drug metabolizing enzymes during P. yoelii infection in
      cerebral microvessels of mice. The data obtained depicted a clear cut impairment
      of cytochrome P450 (a terminal monooxygenase) and related indices viz b5,
      benzopyrene hydroxylase, aminopyrene-n-demethylase, aniline hydroxylase except
      NADH cytochrome e reductase which increased during P. yoelii infection in mice as
      compared to normal. Further the oral drug administration (arteether) treatment
      brought back the altered MFO system normal a week alter cessation of drug
      treatment.

PMID- 16637401
TI  - Risk taking behavior and Sexually Transmitted Diseases: a study among men.
AB  - Sexually Transmitted Diseases (STDs) among men not only jeopardize their own
      health but also increase sexual morbidities among their spouses. STDs are
      primarily attributed to high-risk sexual behavior. The study was carried out
      among male patients attending the OPD of a Government dispensary. Risk taking
      behavior was assessed using a structured, pre-tested questionnaire and STDs were
      diagnosed using syndromic approach supported by laboratory investigations. Three
      hundred two men were selected by systemic random sampling for inclusion in the
      study. 39% had pre-marital sexual relationship, 20% had sex with Commercial Sex
      Workers. 12% of the married men had extramarital sex mostly with CSWs. 27% had
      more than one sex partner ever. Only 3.6% used condoms consistently. Thirteen per
      cent respondents had history of symptoms suggestive of STDs. Prevalence of
      syphilis, gonorrhea and other STDs among study subjects were 3.6%, 0.7% and 0.7%
      respectively. High risk sexual behavior is widely prevalent and STDs are also
      common. Behavior change communication and early diagnosis and prompt treatment of
      STDs will reduce the burden significantly.

PMID- 16637402
TI  - Antimicrobial resistance profile of bacterial isolates from Intensive Care Unit:
      changing trends.
AB  - The incidence of antimicrobial resistance has increased over the years resulting
      in limitation of therapeutic options. Strategies such as appropriate infection
      control measures and surveillance of resistance pattern are necessary to address
      the problem of resistance. Knowledge of the pattern of resistance in Intensive
      Care Units (ICUs) can help to determine antibiotic prescribing policy. A
      retrospective study has been carried out to determine the bacterial spectrum and
      the antibiotic resistance pattern of clinical isolates collected from patients
      admitted to the ICU. The data was compared with a similar study conducted during
      1996-97. Amongst the gram-positive organisms Staphylococcus aureus (23%) was the
      predominant isolate, while Pseudomonas (23%), Acinetobacter (20.8%), Citrobacter
      (11.7%) accounted for the majority of the gram-negative organisms. Both gram
      positive and gram-negative organisms exhibited high resistance to most
      antimicrobial agents used for testing susceptibility. The frequency of resistance
      has markedly increased as compared to the previous study.

PMID- 16637403
TI  - Profile of animal bite cases in Pune.
AB  - A Cross-sectional study was carried out to determine the profile of animal bite
      cases reporting to the Anti Rabies clinic of Sassoon Hospital, rune. The data was
      collected using pretested questionnaire. All 250 cases who reported during the
      period of study were included in the analysis. The male female ratio was 1.98 :
      1. Children in the age group 0-14 years were the victims in 132 (52.8%) cases.
      Dog was the biting animal in 94.4% cases, followed by cat (2.4%), Jackal (1.2%),
      mongoose (1.2%), monkey (0.4%) and horse (0.4%). Of the 236 dog bite cases 30% of
      bites were inflicted by pet dogs of which only 38.02% were immunized. The wound
      was washed with soap and water in only 3.6% of cases. 64.8% of the bites were on
      the lower extremity and 63.2% of cases reported within 24 hours of the bite. Of
      the 247 cases administered Beta Propio Lactone (BPL) inactivated vaccine only
      18.8% did not have any local reaction and 58.3% had one or more systemic
      reaction. A three pronged strategy has been recommended to reduce the burden of
      morbidity and mortality associated with rabies.

PMID- 16637404
TI  - Co-infection by human immuno deficiency virus, hepatitis B and hepatitis C virus
      in injecting drug users.
AB  - Injecting drug users (IDUs) are at risk of parenterally transmitted diseases such
      as hepatitis B virus (HBV) hepatitis C virus (HCV) and human immunodeficiency
      virus (HIV) infections. The present study was undertaken to find out the
      prevalence of HIV infection, HBV infection and HCV infection among IDUs of a
      deaddiction centre. Serum samples from 250, injecting drug users (IDUs) from a de
      addiction centre were screened for HBsAg using immunochromatography, anti HCV
      antibody by 3rd generation ELISA test and anti HIV antibody by ELISA test and
      immunochromatographic rapid test during the period August to October 2002. One
      hundred and forty-nine (59.6%) IDUs were positive for HIV antibody, 226 (90.4%)
      were positive for anti HCV antibody and 27 (10.8%) were positive for HBsAg. There
      was co-infection of HIV, HBV and HCV in 15 (6%) of the IDUs. The Co-infection of
      HBV and HCV were found in 12 cases (4.8%) and Co-infection of HIV and HCV was
      found in 131 cases (52.4%). The IDUs were in sexually active age group with a
      risk of infection to their sexual partner. There is high prevalence of HCV and
      HIV infection and co-infection of both viruses among IDUs. Comprehensive public
      health interventions targeting this population and their sexual partners must be
      encouraged. Increase coverage of needle, syringe exchange programme (NSEP) to
      young and new IDUs is required before they are exposed to blood borne viruses.

PMID- 16637405
TI  - An outbreak of Japanese encephalitis in Haryana.

PMID- 16637406
TI  - Will more of us be working forever? The 2006 Retirement Confidence Survey.

PMID- 16637407
TI  - [When will we get reform?].

PMID- 16637408
TI  - [Home legislation should not distinguish between alliance and property and become
      commonplace].

PMID- 16637409
TI  - [Nursing insurance and politics].

PMID- 16637411
TI  - [Financing nursing insurance--but how:?].

PMID- 16637410
TI  - [On reform of nursing insurance. The position of the German Professional Society
      for Nursing Affairs].

PMID- 16637412
TI  - [e-Health at the will of patients and nurses].

PMID- 16637413
TI  - [When work gets on your nerves].

PMID- 16637414
TI  - [What are the controls for failures in the field of community health nursing?].

PMID- 16637415
TI  - [Beware of poison! Softening in intensive care].

PMID- 16637416
TI  - [The right to visitors. Initiative for unlocking the intensive care unit].

PMID- 16637417
TI  - [How one immediately turns a matter to an obligation].

PMID- 16637418
TI  - [Experience versus arriving too late].

PMID- 16637419
TI  - [Ginkgo at low concentrations].

PMID- 16637420
TI  - [Shoemaker--stay at your last].

PMID- 16637421
TI  - [On the standards of this Journal].

PMID- 16637422
TI  - [On the standards of this Journal].

PMID- 16637423
TI  - [On the standards of this Journal].

PMID- 16637424
TI  - [Cerebellar hematomas. Description of a cohort and prognosis based on therapeutic
      attitude].
AB  - OBJECTIVES: Spontaneous cerebellar hematomas (CH) represent 5%-10% of
      intracranial hemorrhaging. We describe the existing cardiovascular risk factors,
      clinical presentation of CH and its relationship with mortality and the
      association between the treatment type (conservative medical or neurosurgical
      treatment) and the subsequent course of the patients. DESIGN AND SCOPE:
      Observational study of patients diagnosed of CH admitted over three years in an
      Intensive Care Unit of a level III Hospital. PATIENTS: Fifty-six consecutive
      patients diagnosed of CH. VARIABLES OF PRINCIPAL INTEREST: We studied the
      cardiovascular risk factors, presentation form (with Glasgow Coma Scale- GCS),
      hematoma size and site, and morbidity-mortality of the patients (with the Glasgow
      Outcome Scale--GOS). RESULTS: Fisher's exact test, Chi squared, calculation of
      Spearman's coefficient between certain variables and logistic regression analysis
      were used. Hematoma size, GCS on admission and presence of hydrocephaly obtained
      statistical significance. Conservative medical treatment has greater mortality.
      CONCLUSIONS: Patients with GCS < or = 8 and hematoma size > or = 3 cm benefit
      from surgical treatment. Initial GCS and vermian site are mortality predictor
      factors. There is no more morbidity due to surgical treatment.

PMID- 16637425
TI  - [Cohort study on incidence of ARDS in patients admitted to the ICU and prognostic
      factors of mortality].
AB  - OBJECTIVE: Analyze acute respiratory distress syndrome (ARDS) in patients
      admitted to an Intensive Care Medicine Service (ICMS) and prognostic factors of
      mortality in these patients. DESIGN: Prospective study of all the patients
      admitted consecutively in the ICMS from January 1998 to February 2003. SCOPE:
      ICMS of a third level university site with 32 beds in its General Area and 10
      beds in the Traumatology Area. PATIENTS: Patients who met the ARDS criteria of
      the European-North American Consensus Conference at any time during admission in
      ICMS. ENDPOINTS OF INTEREST: Mortality at 28 days. RESULTS: One hundred and
      ninety-one patients (3.4 of all the admissions in ICMS) had ARDS criteria. The
      origin of ARDS was intrapulmonary in 63%. A total of 77% of the patients had
      multiorgan dysfunction and 26% respiratory superinfection. Median stay in the
      ICMS was 20 days. Mortality at 28 days was 48% and hospital mortality 58%.
      Multivariant analysis showed that the variables associated independently with an
      increase in mortality were the following: APACHE II > 22 (odds ratio [OR] 2.7;
      95% CI: 1.3-5.8; p = 0.007), minimum PaO2/FIO2 during evolution of ARDS < 81 mmHg
      (odds ratio 5.5; 95% CI: 2.6-11.9; p < 0.0001), dysfunction > or = 3 organs (odds
      ratio 11.8; 95% CI: 2.5-55.4; p = 0.002). CONCLUSIONS: ARDS is an entity with
      elevated mortality whose prognosis is associated not only with the seriousness of
      pulmonary function deterioration but also of systemic function, on which some
      treatment could modulate its evolution.

PMID- 16637426
TI  - [Neurogenic stunned myocardium].
AB  - The existence of stunned myocardium and reversible myocardial dysfunction is
      widely described and accepted in patients suffering ischemic heart disease.
      However, it cannot be exclusive to coronary disease. Classically, the appearance
      of electrocardiographic changes in the critical neurological disease has been
      described. However, at present, it seems to be observed that some of these
      patients with critical neurological disease could have variable grades of
      myocardial dysfunction, which is generally reversible in the surviving patients.
      This myocardial dysfunction, which could affect critically ill neurological
      patients, has traits similar to stunned myocardium generated in coronary patients
      since: a) it is generally associated to electrocardiographic changes, b) it can
      be accompanied by segmental contractility disorders and even c) it may be
      accompanied by a certain increase of cardiac biomarkers. Although its
      etiopathogeny is unknown, it could be related with the severity of the primary
      neurological disease. Its prophylaxis and prognosis are also unknown. It could be
      related with neurogenic edema, with hemodynamic instability, and could also play
      a very important role in brain death and in organ donation.

PMID- 16637427
TI  - [The eternal promise of high frequency ventilation].
AB  - High frequency oscillatory ventilation (HFOV) is based on the application of
      continuous pressure in the respiratory system, which assures oxygenation, on
      which a small oscillation that permits ventilation is added. Although this
      ventilation form seems to comply with the requirements necessary to minimize the
      pulmonary lesion associated to mechanical ventilator-induced lung injury in acute
      lung injury, as several experimental studies suggest, its advantages in the
      clinical practice must still be demonstrated. Part of this lack of evidence is
      due to methodological problems of the studies published. However, the major
      limitation is that it has not been compared against a conventional ventilation
      strategy with low volumes/pressures. At present, it seems that high frequency
      ventilation is limited to cases refractory to conventional ventilation. A more
      extensive knowledge on how to optimize high frequency ventilation is needed
      before proposing clinical trials having greater scope.

PMID- 16637428
TI  - [Utility of inhaled nitric oxide in patient with acute respiratory distress
      syndrome and un-operated Fallot's tetralogy].
AB  - Utility of inhaled nitric oxide in the treatment of acute respiratory distress
      syndrome (ARDS) with pulmonary hypertension (PHT) is controversial and there are
      few studies in the literature that evaluate its effects during prolonged
      administration. We analyze the case of a 45 day old male patient with un-operated
      Fallot's tetralogy who developed ARDS and PHT with non-cardiac cause, that
      required prolonged mechanical ventilation (30 days) and administration of inhaled
      nitric oxide (INO). Before the INO, the oxygenation index was 19, and at a few
      minutes of its application it decreased to 15. The patient developed a dependence
      on INO, tolerating its gradual weaning. Administration could be interrupted at 27
      days on onset. We did not observe toxic effects during the administration of INO.

PMID- 16637429
TI  - [Acute parotiditis after tracheostomy in Intensive Care].
AB  - Post-anesthesic parotiditis is a little known entity related with anesthesic
      procedures but described in any situation that motivates manipulation of the
      oropharyngeal cavity. Its physiopathological mechanism is not well-defined,
      although it could have a multifactorial origin. A case of a male who was admitted
      for post-operative control of brain tumor exeresis and who had preauricular and
      submaxillary inflammation after a routinely performed tracheostomy is presented.
      Coincidence with the performing of a tracheostomy required us to propose the
      differential diagnosis with the complications associated to said surgical act.
      Post-anesthesic parotiditis, even though it is a rare complication and has no
      clinical significance, should be kept in mind when there is facial edema after
      any manipulation of the oropharyngeal cavity.

PMID- 16637430
TI  - [Epidural hematoma secondary to epidural catheter for analgesia in a
      polytraumatized patient].

PMID- 16637431
TI  - [Brachial plexopathy secondary to subclavian venopuncture for implant of final
      pacemakers].

PMID- 16637433
TI  - Pathogenic bacteria carried by companion animals and their susceptibility to
      antibacterial agents.
AB  - Results of the investigation showed that there was a difference in the bacteria
      isolated from dogs, cats and their living environment. The number and species
      isolated from the hair and front paw samples from dogs kept outdoors and from
      cats were greater and more varied than those from the samples from dogs kept
      indoors. Staphylococcus, Micrococcus and Bacillus were frequently detected from
      skin surfaces. On the other hand, Escherichia, Pseudomonas, Proteus and others
      were detected on each sampling area on dogs kept outdoors and on cats. About 60%
      of the bacteria commonly causes infectious diseases and carries a risk of food
      poisoning. Moreover, Pasteurella multocida, which causes pasteurellasis, a kind
      of zoonosis, was isolated from dogs and cats. These pathogenic bacteria were
      transmitted from animals to humans by direct contact. This result suggests that
      direct contact with dogs and cats and contact with aerosols can possibly transmit
      infectious diseases. Most of the isolates (75.9%, 60/79) were resistant to
      antibacterial agents. We then investigated the effect of household detergents and
      pet care deodorant sprays containing antibacterial agents on isolates from dogs
      and cats. They were effective in preventing the transmission of pathogens from
      dogs and cats to humans.

PMID- 16637434
TI  - Relationship between the contamination of the nurse's caps and their period of
      use in terms of microorganism numbers.
AB  - Nosocomial infections are a great problem in the health care facilities. The
      white uniforms of nurses are often washed to keep them clean, but the nurse's
      caps are not washed as frequently in comparison. It could be that the importance
      of these caps is being overlooked. If these caps are providing a residence for
      microorganisms causing nosocomial infection in the health care facility, then
      they should be washed as frequently as the uniforms. So far, the relationship
      between the contamination of the nurse's caps and nosocomial infection has not
      yet been studied. Therefore, this study was conducted to confirm if relationships
      exist among factors regarding the number of microorganisms on the nurse's caps,
      the period in which caps were used without being washed, and the individual
      characteristics of nurse wearing the caps. Results showed that the degree of
      contamination of the nurse's caps depended on individual characteristics and the
      period of use. Finally, results led to the conclusion that the nurse's caps
      should not be worn if their only purpose is to symbolize female workers in the
      health care facilities because, in actually, they provide a resistance for
      microorganisms causing nosocomial infections.

PMID- 16637435
TI  - Sterilization efficiency of the photocatalyst against environmental
      microorganisms in a health care facility.
AB  - The photocatalyst equipment consists of a titanium dioxide membrane and an
      ultraviolet lamp. The authors studied if the photocatalyst equipment is
      practically useful in sterilizing environmental microorganisms in the health care
      facility. The number of microorganisms was compared in the cases of no
      sterilization (control) and the photocatalyst sterilization. As a result, a
      statistical difference was observed between control and the photocatalyst
      sterilization against airborne microorganisms (p < 0.01), but not against surface
      microorganisms (p > 0.2). The photocatalyst uses an air sucking system, so it may
      be ineffective against microorganisms tightly attached to surfaces. However, the
      effectiveness of the photocatalyst to sterilize airborne microorganisms in the
      health care facility was successfully confirmed. Concerning the humidity effect
      on the photocatalyst sterilization, the authors compared the number of airborne
      microorganisms in cases of the control, UV alone and photocatalyst sterilization
      when humidity was changed. A statistical difference was observed between UV and
      the photocatalyst sterilization (p < 0.01) when humidity was increased to 60-70%,
      but not observed between UV and the photocatalyst sterilization (p > 0.2) when
      humidity was not controlled and was around 10-20%. This indicates that
      maintaining high humidity levels will present satisfactory sterilization results
      due to a greater production of OH radicals. From data obtained, no effect of the
      adsorption on the TiO2 membrane could be observed.

PMID- 16637436
TI  - Mechanical properties and antibacterial efficacy of chitosan films.
AB  - Chitin, chitosan and quaternary chitosan films were prepared, and the mechanical
      properties and the antibacterial activities of chitosan and quaternary chitosan
      films were evaluated. The tensile strength of chitin films was 30-40% lower than
      that of chitosan films, but the crystallinity of the former was much higher than
      those of the latter. A detailed analysis of the crystallinity and orientation of
      crystallites of chitosan films revealed that the cast film prepared with acetic
      acid provided a little lower crystallinity than the others. The antibacterial
      activities of quaternary chitosan films against Staphylococcus aureus and
      Escherichia coil were stronger than those of chitosan films. The antibacterial
      activities of neutralized chitosan films may be slightly inferior to those of un
      neutralized chitosan films. The improvement in the antibacterial activity of
      chitosan films against E. coli was slightly inferior to that against S. aureus.
      This phenomenon was particularly observed on the neutralized chitosan films.
      Though the antibacterial activity of chitosan was slightly inferior to that of
      the organic antibacterial compounds, we emphasize that chitosan would be a useful
      and suitable material with regard to its effect on the environmental ecosystem.

PMID- 16637437
TI  - Antifungal characteristics of N,N'-hexamethylenebis (4-carbamoyl-1
      decylpyridinium bromide).
AB  - A bis-quaternary ammonium compound (bis-QAC), N,N'-hexamethylenebis(4-carbamoyl
      1decylpyridinium bromide) (D-38), exhibited a wide antifungal spectrum and a
      strong activity against sixteen strains of fungi including nine strains isolated
      from various kinds of food. The antifungal activity was higher than that of N
      dodecylpyridinium Iodide, a typical mono-QAC, and that of the commonly used
      fungicide, 2-(4-thiazolyl) benzimidazole. The activity of D-38, however, was
      comparatively low when it was measured by the agar dilution method. It is
      considered that the hydrophobic D-38 molecules, having two long alkyl chains,
      interacted with the agar medium, and therefore showed lower activity results. On
      the other hand, the activity of D-38 against Aspergillus niger IFO 6342 was not
      significantly influenced by temperature, pH and the initial spore concentration.
      These results indicate that bis-QACs can exhibit a high antifungal activity
      whether or not the environmental conditions change.

PMID- 16637438
TI  - Spoilage ability of psychrotrophic Paenibacillus spp. isolated from cooked food
      products.
AB  - Five spore-forming bacterial strains were isolated as the most dominant
      microorganisms from five products of different types of cooked food. Three
      strains in particular were isolated as spoilage organisms causing acidity. These
      belonged to the genus Paenibacillus, and one of them was identified as
      Paenibacillus odorifer. All five strains grew at 10 degrees C in brain heart
      infusion broth; furthermore, four strains grew at 4 degrees C also. These strains
      grew optimally at 30 to 35 degrees C. Psychrotrophic Paenibacillus spp. can
      easily be mistaken for lactic acid bacteria in routine analysis because of their
      colony characteristics. Because the measures that must be taken for bacterial
      control are different in the case of contamination by these two bacterial groups,
      psychrotrophic Paenibacillus spp. contamination must be distinguished from that
      caused by lactic acid bacteria.

PMID- 16637439
TI  - The Texas Advance Directives Act of 1999: an exercise in futility?

PMID- 16637440
TI  - Futility: revisiting a concept of shared moral judgment.

PMID- 16637441
TI  - Futility revisited: reflections on the perspectives of families, physicians, and
      institutions.

PMID- 16637442
TI  - The fiction of futility: what to do with policy?

PMID- 16637443
TI  - Futility in medical decisions: the word and the concept.

PMID- 16637444
TI  - [Prevention of venous thromboembolism: generally accepted guidelines].
AB  - This article summarizes the published data on the prevention of venous
      thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It
      is recommended to sort patients according the thrombosis risk and to make use of
      the standard prophylactic modes. In low risk patients, no specific
      thromboprophylaxis is needed. Patients with moderate risk levels are candidates
      for administration of subcutaneous low molecular weight heparin (LMWH) at doses
      under 3 400 anti-Xa units a day and patients with increased risk at doses higher
      than 3400 anti-Xa units a day during the period of higher risk. In order to
      decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the
      operation can be administered. Under the highest risk conditions, there is a
      recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose
      or, alternatively, with intermittent pneumatic compression. At moderate risk
      levels, subcutaneous administration of unfractionated heparin at the doses of 5
      000 units twice a day is also possible and at increased risk levels, a TID
      administration over the increased risk period. In patients with a significant
      bleeding risk, the physical method of thromboprophylaxis can be used and
      pharmacological prophylaxis can set in after the risk of bleeding has passed.
      Fondaparinux is the alternative to LMWH in people after major orthopaedic
      surgeries and with a history of heparin induced thrombocytopenia over the past
      three months. An alternative to the administration of LMWH even after the end of
      the hospitalization can be warfarin in certain situations. The sole use of
      acetylsalicylic acid or Rheodextran is not recommended. While undertaking
      epidural anaesthesia or analgesia, it is necessary to follow strictly the
      guidelines of the use of pharmacological thromboprophylaxis.

PMID- 16637445
TI  - [Thrombophilic conditions in the pathogenesis of venous thromboembolism].
AB  - Thrombophilic conditions are congenital or acquired hemostatic disorders
      pathophysiologically or statistically associated with higher risk of thrombosis.
      Their most important clinical manifestation is venous thromboembolism. In more
      than 50% of persons with non-induced thrombosis, some of the known thrombophilias
      can be found. Persons with congenital thrombophilias have, contrary to those
      without any thrombophilias, most of all an increased risk of an initial
      thromboembolic event while the impact of congenital thrombophilic conditions on
      their recurrence is not so clear. In patients with idiopathic thrombosis is the
      risk of recurrence 7-10% a year even at the absence of known thrombophilias. The
      risk of a recurrent event is influenced by a set of other factors (prevailing or
      undetected trigger factor, proximal thrombosis and pulmonary embolism, incomplete
      rechanneling of a thrombotic vein, presence of some thrombophilias, high level of
      D-dimers after discontinuation of the anticoagulant treatment). Their
      identification and consequent monitoring are decisive in the choice of an optimum
      treatment and the duration of their administration in secondary prevention of
      venous thromboembolism. In the primary venous thrombosis prevention, the
      knowledge of general trigger factors and the individual risk characteristics of
      the given patient is important, which means also timely detection of
      thrombophilic conditions in patients who profit from it, i.e. if they display at
      least medium probability of detection. A universal long-term prophylaxis in so
      far asymptomatic carriers of congenital thrombophilias is not indicated with
      regard to potential complications of anticoagulant treatment. Women with
      thrombophilic disorders are under an increased risk of a thromboembolic event
      when using hormonal contraceptives and during pregnancy. There is also a higher
      incidence of pregnancy complications connected with disorders in blood
      circulation of placental vascular tree.

PMID- 16637446
TI  - [Laboratory monitoring of antithrombotic treatment].
AB  - A number of tests can be employed in monitoring anticoagulant, thrombolytic and
      antiaggregation treatment. Not all, however, indicate precisely the therapeutic
      effect of the drug used. Some of them are of linear character and they monitor
      closely the dosage, others have a series of non-specific reactions and the
      therapeutic effect is largely influenced by these circumstances. This article
      describes the individual monitoring systems, it deals with their potential
      reliability issues, and, also, treatment monitoring issues in various diagnostic
      environments are discussed.

PMID- 16637447
TI  - [Pharmacogenetics of warfarin].
AB  - There are significant differences among patients treated with warfarin in the
      dosage volumes necessary to reach an optimum therapeutic effect. Apart from the
      external influences (interactions with drugs and food), genetic predispositions
      play an important role. Polymorphysms of the P 450 2C9 cytochrome bear upon the
      speed ofbreaking down S-warfarin, polymorfysms VKORC1 bear on the volume and
      quality of epoxide reductase--an enzyme whose blockade is the crux of the
      mechanism how cumarin anticoagulants act. These two genes are responsible for at
      least 50% of the warfarin effect variability. Warfarin's effect is further
      determined by the genetic variants of gamma-carboxylase, prothrombin, factors VII
      and IX. In near future, further results of pharmacogenetic research and clinical
      studies can be expected. They study the impact of the findings in clinical
      practice.

PMID- 16637448
TI  - [The preparation of a patient with long-term anticoagulant cumarin treatment for
      invasive surgery].
AB  - Coumarins belong to drugs widely used and the spectrum of their use is going to
      grow. From this point of view and/or because the coumarins are adminstrated in
      patients who are treated for the other diseases--medical or surgical--at the same
      time, it is necessary to modify, interrupt or replace peroral anticoagulant
      treatment in the dependence on various aspects. It requires to compound different
      algorithms for given situations solution. It is always to decide, if the
      situation is imperative from the view of solution planed, what risk brings
      proposed treatment and what is the risk of anticoagulant treatment modification.

PMID- 16637449
TI  - [Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in
      venous surgery and in urology].
AB  - The article summarizes published data regarding the prophylaxis of venous
      thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in
      urology. In surgical patients with low risk, no specific thromboprophylaxis is
      needed. Patients with moderate risk levels are the candidates for administration
      of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa
      units a day and patients with increased risk at doses higher than 3 400 anti-Xa
      units a day during the period of higher risk. In order to decrease the risk of
      bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be
      administered. Under the highest risk conditions, there is a recommendation to
      combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively,
      with intermittent pneumatic compression (IPC). At moderate risk levels,
      subcutaneous administration of unfractionated heparin at the doses of 5 000 units
      twice a day is also possible and at increased risk levels, a TID administration
      (LDUH) over the increased risk period. In patients with a significant bleeding
      risk, the physical method of thromboprophylaxis can be used and pharmacological
      prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the
      alternative to LMWH in people with a history of heparin induced thrombocytopenia
      over the past three months. The sole use of acetylsalycilic acid is not
      recommended. While undertaking epidural anaesthesia or analgesia, it is necessary
      to follow strictly the guidelines of the use of pharmacological
      thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC
      is indicated only in those patients who undergo laparoscopic surgeries and who
      moreover display the additional thrombosis factors. Patients with additional risk
      thrombosis factors undergoing major venous reconstructions require prophylaxis
      with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low
      risk urologic surgery require no specific thromboprophylaxis. If they undergo a
      major intervention and/or they display additional risk thrombosis factors, they
      require the administration of LMWH or LDUH. Elastic panty-hose and/or
      intermittent pneumatic compression have the same indication as in abdominal
      surgeries.

PMID- 16637450
TI  - [Prevention of venous thromboembolism in orthopaedics].
AB  - The incidence of venous thromboembolism in orthopaedic patients is high and its
      prevention deserves special attention. In patients with total hip and knee
      replacements and with the proximal femur fractures, low molecular weight heparin
      should be administered at higher prophylactic dosages. Following its approval,
      pentasaccharide (fondaparinux) should become the drug of choice, especially in
      patients with proximal femur fractures. Pharmacological prophylaxis should take
      at least 10 days in case of total knee replacements and longer in patients with
      increased risk of venous thromboembolism. In patients with total hip replacements
      or with proximal femur fractures, LMWH or pentasaccharide prophylaxis is
      indicated over a period of 28-35 days. Under the conditions of well working
      infrastructure for anticoagulation treatment, there is an alternative of warfarin
      treatment, lasting consequently 6-8 weeks. In patients with proximal femur
      fracture that bleed or are in a very increased risk of bleeding, a possible
      alternative is represented by intermittent pneumatic compression and shift to
      antithrombotic treatment after bleeding stops. In patients with knee
      arthroscopies displaying no risk factors of venous thromboembolism where
      tourniquet was used no longer than 60 minutes, pharmacological prophylaxis is not
      necessary. Only timely mobilisation is recommended. In patients displaying risk
      factors of venous thromboembolism or with tourniquet use surpassing 60 minutes,
      it is advisable to administer low molecular weight heparin in lower prophylactic
      dosage. In patients with lower extremity fractures treated with osteosynthesis,
      LMWH administration of 7-10 days is indicated. In patients with lower extremity
      injuries requiring plaster casting or other type of fixation reaching below the
      knee, LMWH administration is indicated over the whole period of fixation in
      persons with higher risk (people with venous thromboembolism in their histories,
      in direct relative's histories, people with thrombophilic conditions including
      poeple with malignancies, women using hormonal contraceptives or their
      substitutions). Aspirin is not a suitable drug for separate administration in the
      prophylaxis of venous thromboembolism in orthopaedic patients.

PMID- 16637451
TI  - [Antithrombotic prophylaxis and treatment in thrombophilic disorders in
      gynaecology and obstetrics].
AB  - Pregnancy and puerperium are physiological thrombophilic condition and risk of
      venous thromboembolism in pregnancy is 4 - 6 fold higher. This risk is further
      increased in the presence of the additional risk factors. Inherited thrombophilia
      is well-defined risk factor for VTE in pregnancy and also can be the risk for
      obstetrics complications. So that early diagnostic of inherited thrombophilia can
      result in the decrease of risk of VTE and the obstetrics complications.

PMID- 16637452
TI  - [Prevention of venous thromboembolism in internal medicine and neurology].
AB  - Many hospitalized patients are under an increased risk of venous thromboembolism.
      They should have adequate pharmacological prophylaxis. Clinical studies including
      meta-analyses prove that low molecular weight heparin prophylaxis of venous
      thromboembolisms is equally effective as that employing unfractionated heparin
      and it features less bleeding complications. The effectiveness of pharmacological
      prophylaxis with low molecular weight heparin in hospitalized patients at
      internal medicine departments has been proven by the MEDENOX study when
      enoxaparin in a dose of 40 mg was administered subcutaneously and the PREVENT
      study when subcutaneous dalteparin 5 000 units j. was administered daily. In the
      MEDENOX study, enoxaparin administration was confirmed to decrease the relative
      risk of venous thromboembolisms by 63% without increasing any adverse effects
      during the prophylaxis and the PREVENT study showed that dalteparin
      administration was followed by a highly significant reduction of asymptomatic
      venous thromboses in hospitalized patients. According the ACCP guideline for
      thromboprophylaxis in hospitalized internal medicine patients with clinical risk
      factor of venous thromboembolism (tumors, heart failures, sepsis, VTE history and
      serious pulmonary condition), low molecular weight heparin or mini-doses of
      unfractionated heparin are to be administered. The recent recommendations
      discourage the use of acetyl-salicylic acid in monotherapy treatment for venous
      thromboembolism prevention.

PMID- 16637453
TI  - [Prevention of venous thromboembolism in paediatry].
AB  - Data in Canadian registry for VTE in children show, that incidence of VTE in
      children is 0.07/10 000. The situation in adults--with incidence of VTE 37/10 000
      -is however completely different. Only 5% of VTE in children are idiopathic and
      less then 10% are related to hereditary prothrombotic risk factors only. In other
      words, more than 80% of VTE in children are somehow related to acquired
      prothrombotic risk factors. Despite of this, there have not been found any
      measures, that would be able to further decrease significantly this very low
      incidence of VTE in children. This is probably the reason, why to date there are
      no evidence based recommendations for primary prophylaxis of VTE in children and
      also there is no valid reason for non-selective screening for hereditary
      prothrombotic risk factors in population of children, who have not suffered VTE.

PMID- 16637454
TI  - [Prevention of venous thromboembolism in psychiatry].
AB  - The hospitalized patients of the psychiatric wards represent a risk group for the
      development of venous thromboembolism. Apart from sedative administration, total
      movement reduction, bad life style and daily routine and increased body weight,
      there is negative impact of dehydration, prolonged hospitalization and sometimes
      immobilisation in consequence of mechanical restraints. A large amount of
      patients are treated with antipsychotics that have a series of adverse effects.
      Depending of the drug used, the most frequent of them are somnolence, fatigue,
      extrapyramidal syndrome, hypotension, hepatotoxicity, increased body weight,
      prolongation of the QT interval of the ECG with a risk of ventricular
      arrhythmias, hematopoietic disorders, lipid or glycide metabolism disorders or
      hyperprolactinemia. Another potential adverse effect of these drugs is the
      heightened risk of venous thromboembolism development (deep vein thrombosis
      and/or pulmonary embolism). There is the risk of a pathological blood clotting
      event in psychiatric patients, especially those treated with antipsychotics.
      Although it is not high, it can have fatal consequences when combined with a
      relatively frequent pulmonary embolism and difficult diagnostics of
      thromboembolism. An algorithm for thromboembolism prevention has been developed.
      It involves important general risk factors of venous thrombosis (VTE history,
      immobilisation, malignancy, age over 75 years etc.) and also markers (physical
      restraints, dehydration, obesity, antipsychotics use) that can participate in the
      pathogenesis of venous thrombosis in the hospitalized psychiatric patients with
      limited motility. The authors believe that this prophylaxis is indicated, safe,
      effective and that it improves the quality of life at relatively low costs.

PMID- 16637455
TI  - [Hemorrhagic complications during warfarin treatment].
AB  - Bleeding is probably the major complication of anticoagulant treatment with
      vitamin K antagonists represented nowadays mostly by warfarin in the Czech
      Republic. The main risk factors in hemorrhagic complications of warfarinisation
      are the intensity and instability of the anticoagulant treatment, individual
      patient characteristics, warfarin interactions with other drugs and the length of
      the anticoagulant therapy. Severe bleeding in warfarin patients is most
      effectively brought about by a fast and complete undoing of the anticoagulation
      effect of the drug employing the prothrombin complex concentrate and slow i.v.
      vitamin K1 infusion regardless of the reason for the anticoagulation. This
      approach can secure the minimalisation of the bleeding's negative consequences. A
      less severe bleeding or asymptomatic increase in the international normalized
      ratio can be treated effectively by skipping or decreasing of the warfarin dosage
      and/or oral administration of vitamin K1 (i.v. administration only in selected
      higher risk cases) that does result only in a partial consolidation of
      coagulopathy but of such type that the risk of thrombotic event requires. The
      article's goal is to contribute to the treatment standardization in patients with
      warfarin overdose and/or with hemorrhagic complications due to warfarin treatment
      and it is available at www.thrombosis.cz. The guidelines include a ready
      reference chart whose objective is immediate and quick crash course in the
      clinical practice.

PMID- 16637456
TI  - [Complications of heparin administration].
AB  - Heparin as an indirect anticoagulant is used in the clinical practice for more
      than 60 years. It is an effective drug, but it has limitations. To the side
      effects belong the heparin resistance, risk of bleeding (haemorrhage),
      hypersensitivity reactions and heparin-induced osteoporosis. The low-molecular
      weight heparins exhibit fewer side effects, but it is still necessary to know
      about them.

PMID- 16637457
TI  - [Heparin induced thrombocytopenia].
AB  - This article describes the pathogenesis, diagnostics, treatment and prevention of
      heparin induced thrombocytopenia (HIT). Although HIT is considered to be a
      hematological diagnosis, every physician who treats patients with heparin can
      encounter it in daily practice. It is even more probable that surgeons of any
      specialisation will meet with HIT patients. A section of them elude diagnostic
      detection. There are two forms of HIT - HIT I and HIT II. HIT I is caused by a
      direct pro-aggregation effect of heparin. It has no clinic significance. HIT II
      is an antidote mediated adverse reaction to heparin. Antidotes will generate only
      after the exposure to heparin. They are targeted against the platelet factor 4
      and they act only at the presence of heparin. They may lead to the aggregation of
      thrombocytes in the vascular system (there is a decrease in thrombocyte count).
      This event can be accompanied by a development of venous or arterial thrombosis
      that can have a rapid and even fatal course. This fact clarifies the importance
      of HIT II diagnostics. Diagnosis of HIT II is based on recognizing of the typical
      decrease in thrombocyte count usually 1 day after heparin administration is
      initiated. Clinical manifestations are more likely in patients with already
      damaged endothelium. If thrombocyte count decrease is not connected with clinical
      manifestations, it is the so called isolated HIT II and in patients who display
      the signs of thrombosis, it is HIT II associated with thrombosis. The goal of
      this article is apart from implementing the recommendations of the 7th conference
      of the American Respiratory Society in real life also the exploration of the
      diagnostic and therapeutic limits (availability) in the Czech Republic.

PMID- 16637458
TI  - [Anticoagulant treatment failure].
AB  - Anticoagulant therapy includes unfractionated heparin and vitamin K antagonists'
      administration. In both of these two types of drugs a treatment failure could
      occur. Currently available anticoagulants have a numerous disadvantages which
      could be involved in causes of their malfunctioning. During every new event of
      the re-thrombosis it is necessary to analyse all circumstances which influence
      this unfavourable outcome. Firstly, cases during adequate and non-adequate
      therapy should be distinguished. Secondly, it is important to identify the
      reasons of the treatment failure. Cancer and/or antiphospholipid antibodies are
      the main causes of re-thrombosis during adequate therapy. The conditions, which
      could steer for to non-adequate anticoagulation are various, and their
      identification could be difficult. The most important thing in this process is
      the objective documentation of the re-thrombosis. More efficacious, safer, and
      easier to use anticoagulants are under development. Some of them could bring a
      problem solution for these patients who underwent anticoagulant treatment
      failure.

PMID- 16637459
TI  - Emerging anticoagulants: mechanism of action and future potential.
AB  - Medical needs associated with diverse thromboembolic conditions are not fully met
      by currently available anticoagulants. Of those, unfractionated heparin (UFH) is
      gradually replaced by low molecular weight heparin (LMWH) for prevention and
      treatment of venous thromboembolism and acute coronary syndromes, along with
      supportive treatment with oral anticoagulants, such as warfarin derivatives.
      While generally effective these agents have several shortcomings involving
      compliance, delivery, efficacy and safety considerations in various disease
      settings, and for these reasons new anticoagulants are sought, to target more
      specifically the critical effectors and steps in the blood coagulation process,
      namely: (i) initiation, (ii) propagation and (iii) the phase of thrombin
      activity. The emerging agents that block tissue factor/factor VIIa-dependent
      initiation phase of the coagulation cascade, include: recombinant tissue factor
      pathway inhibitor (rTFPI), nematode anticoagulant peptide (NAPc2), active site
      blocked factor VIIa (FVIIai) and TF targeting antibodies. Some of them are
      currently evaluated in clinical trials with promising results. Propagation phase
      of thrombus formation (e.g. the activity of factors IXa, Xa, VIIIa or Va) is
      targeted mainly by various indirect, direct and bimodal inhibitors, such as
      fondaparinux, indraparinux, tick anticoagulant peptide (TAP), antistatin (ANT)
      and antithrombin-heparin covalent complex (ATH), all endowed mostly with an anti
      Xa activity. Although promising, some of these agents (TAP, ANT and ATH) have not
      progressed beyond animal testing while others (fondaparinux) was already assessed
      for prevention and treatment of venous thromboembolism and for treatment of
      arterial thrombosis. Lastly, inhibitors of thrombin activity are composed of
      either indirect (UFH, LMWH), or direct thrombin (FIIa) inhibitors including:
      hirudin, argatroban, melagatran, ximelagatran, dabigatran, and bivalirudin. These
      agents are either in advanced development or already approved for clinical use.
      Bimodal FIIa inhibitory activity of ATH was demonstrated in animal models of
      venous and arterial thrombosis, but is in need of further development. In
      conclusion, while some of these emerging anticoagulants, such as fondaparinux,
      idraparinux, ximelagatran and ATH appear to possess superior efficacy-safety
      profile, as compared to their conventional predecessors (UFH, LMWH and warfarin),
      their cost-effectiveness, side effects and antidote availability have to be
      considered. More importantly, coagulation factors that are targets of these
      inhibitory activities also affect coagulation independent processes, such as
      wound healing, inflammation, angiogenesis, mitogenesis and cell survival. Thus
      the consequences of both coagulation-dependent and -independent effects of new
      agents should be carefully considered before proper clinical indications are
      established.

PMID- 16637460
TI  - Clinical trials of new anticoagulants.
AB  - Shortcomings of the existing anticoagulants, vitamin K antagonists and heparins,
      have led to the development of newer anticoagulant therapies. In particular,
      Vitamin K antagonists' slow onset of action, numerous drug interactions, narrow
      therapeutic window and need for frequent monitoring make it the most obvious
      target for replacement. Targeting specific coagulation enzymes or steps in the
      coagulation pathway, new anticoagulants have been or are under evaluation in
      clinical trials for a number of clinical indications, namely the prevention and
      treatment of venous thromboembolism, the prevention of ischemic stroke in
      patients with atrial fibrillation, and in acute coronary syndromes. Following a
      brief review of pharmacological aspects, this article will summarize the results
      of Phase III clinical trials evaluating the novel anticoagulants fondaparinux,
      ximelagatran and idraparinux. At present, most attention is directed at
      developing an oral anticoagulant to replace vitamin K antagonists for prevention
      of systemic thromboembolism. A number of newer agents are in both early and
      advanced stages of investigation.

PMID- 16637461
TI  - Venous thromboembolism and cancer: prevention and therapy.
AB  - Venous thromboembolism (VTE) is a common problem in patients with cancer that
      complicates management and predicts for a worse prognosis. Hence, effective
      methods to prevent and treat VTE can reduce morbidity and mortality. Low
      molecular weight heparins have simplified and improved management of VTE and
      recent studies suggest these agents may improve survival in cancer patients. This
      review will provide an update on the primary prevention and treatment of VTE, as
      well as prophylaxis for central venous catheters, in patients with malignancy.

PMID- 16637462
TI  - Risk of thrombosis in pediatric ALL patients--is there a problem!

PMID- 16637463
TI  - Genetic determinants of cancer coagulopathy, angiogenesis and disease
      progression.
AB  - Progression of human malignancies is accompanied by vascular events, such as
      formation and remodeling of blood vessels and systemic coagulopathy. Though long
      appreciated as comorbidity of cancer (Trousseau syndrome), vascular involvement
      is increasingly recognized as a central pathogenetic mechanism of tumor growth,
      invasion and metastasis. The major outstanding question in relation to this role
      has been, whether vascular perturbations are simply a reaction to the conditions
      of the tumor microenvironment, or are linked to the known genetic lesions causal
      for the onset and progression of malignancy. In this regard, we have previously
      hypothesized, and recently demonstrated experimentally that deregulation of
      certain hemostatic mechanisms, namely upregulation of tissue factor (TF) and
      possibly other changes (e.g. expression of thrombin receptor - PAR-1) are
      controlled by cancer-associated oncogenic events, such as activation of K-ras,
      epidermal growth factor receptor (EGFR), or inactivation of the p53 tumor
      suppressor gene in various human cancer cells. It appears that these respective
      transforming alterations exert their impact on both, cell-associated and
      soluble/circulating (microvesicle- associated) TF, i.e. may cause a systemic
      hypercoagulable state. Other genes, which more recently emerged as regulators of
      cancer coagulopathy include: PML-RARalpha, PTEN, and MET. While the spectrum of
      procoagulant targets of these genes may vary somewhat it includes: TF, PAI-1, COX
      2 and possibly other hemostatic proteins. It is noteworthy that these
      prothrombotic changes may impact the malignant process directly (e.g. stimulate
      angiogenesis, tumor growth or metastasis) as a consequence of both coagulation
      dependent and -independent effects. The latter are mostly related to cellular
      signaling events and changes in gene expression which are now known to be induced
      by the TF/FVIIa/Xa complex, thrombin and PARs, expressed on the surface of cancer
      cells, as well as tumor-associated endothelium. Interestingly, certain
      anticoagulants possess antimetastatic and anticancer properties (e.g. LMWH), an
      observation that further suggests that hypercoagulability may act as an effector
      mechanism of genetically driven tumor progression. Conversely, we suggest that
      oncogene-directed (targeted) anticancer agents could, at least in some cases,
      ameliorate not only cellular transformation itself, but also some of the chronic
      components of the cancer-related coagulopathy, something that may be relevant to
      therapeutic efficacy of these drugs. We also postulate that since TF is the
      oncogene target, circulating TF (microparticles) could serve as surrogate marker
      of the biological activity oncogene-directed agents exert in vivo. Thus, both
      genetic and epigenetic factors appear to conspire to activate various components
      of the hemostatic system in cancer patients, both locally and systemically. These
      activities act as mediators of cancer coagulopathy, angiogenesis, metastasis and
      other events involved in disease progression and should be recognized in
      designing better anticancer therapies.

PMID- 16637464
TI  - Scientific fraud--real consequences.

PMID- 16637465
TI  - The dental team: A ready reserve or an overlooked resource?

PMID- 16637466
TI  - Local anesthesia and informed consent.

PMID- 16637467
TI  - More about informed consent.

PMID- 16637468
TI  - Abfractions.

PMID- 16637469
TI  - Bisphosphonate-associated osteonecrosis.

PMID- 16637470
TI  - Thanks to AAOM.

PMID- 16637471
TI  - More about BON.

PMID- 16637472
TI  - Periodontal disease onset in children with diabetes earlier than thought.

PMID- 16637473
TI  - The smallpox vaccine: An update for oral health care professionals.
AB  - BACKGROUND: A heightened awareness of the potential for bioterrorist attacks in
      the United States has led to the expansion of the nation's supply of smallpox
      vaccine and the institution of procedures to distribute this vaccine in the
      unlikely event of a release of this potentially deadly agent. METHODS: The
      authors conducted a review of the relevant smallpox literature through a MEDLINE
      search. They also reviewed the Web site of the Centers for Disease Control and
      Prevention and numerous other Web sites. RESULTS: The authors considered for
      inclusion more than 100 articles discussing smallpox, the smallpox vaccine and
      the role of the dental professional in a bioterrorist attack. CONCLUSIONS:
      Dentists may detect the initial signs of a smallpox infection, provide
      information concerning the disease to the public and potentially assist in the
      administration of smallpox vaccine. CLINICAL IMPLICATIONS: Should an intentional
      release of smallpox occur, the dental professional may play an important role in
      its treatment and prevention.

PMID- 16637474
TI  - Dentists' preparedness for responding to bioterrorism: A survey of Hawaii
      dentists.
AB  - BACKGROUND: The authors conducted a survey of dentists in Hawaii to assess their
      knowledge of, perceived readiness for and willingness to respond to bioterrorist
      (BT) events. METHODS: Using a cross-sectional study design to access a random
      sample (n = 240) of all licensed dentists residing in the state of Hawaii (N =
      1,016), the authors mailed study participants an anonymous survey up to three
      times during June and July 2004. Knowledge-based questions were taken from
      accredited Internet-based free continuing medical education offerings. RESULTS:
      Of 234 deliverable surveys, 133 were returned (response rate of 56.8 percent).
      Only 2.3 percent of respondents reported having received prior BT preparedness
      training. A total of 14.5 percent felt able to identify and recognize a BT event,
      and 9.2 percent indicated they were able to respond effectively to a BT attack. A
      total of 73.8 percent expressed willingness to provide assistance to the state in
      the event of a BT attack. Dentists scored a mean of 62 percent correct (5.6 of
      nine questions) on the objective knowledge-based questions. CONCLUSIONS: A low
      prevalence of prior training coupled with a high degree of willingness to provide
      assistance indicates the need for additional BT preparedness training. This
      should be provided as continuing education offerings to practicing dentists and
      incorporated into the dental school curriculum. CLINICAL IMPLICATIONS: Dentists
      have the basic knowledge and experience to perform a number of key roles in a BT
      event; however, additional training must be provided to develop BT preparedness
      competencies.

PMID- 16637475
TI  - The dental emergency responder: Expanding the scope of dental practice.
AB  - BACKGROUND: Natural disasters, the potential for terrorism and weapons-of-mass
      destruction events occurring within the continental United States necessitate
      that all licensed health care providers understand the National Incident
      Management System and be able to contribute to inoculation, mass casualty
      assistance and triage care of the populace. CONCLUSIONS: Health care and
      political leaders constantly revise "all hazard" response plans, using the
      available health care assets that local, state and federal agencies bring to
      emergency events. Illinois Public Act 49-409 modifies the scope of dental
      practice within Illinois to allow for a dental emergency responder (DER).
      PRACTICE IMPLICATIONS: The DER is a dentist or dental hygienist "acting within
      the bounds of his or her license when providing care during a declared local,
      state or national emergency."

PMID- 16637476
TI  - Oral manifestations of aplastic anemia in children.
AB  - BACKGROUND: Few studies concerning oral manifestations of aplastic anemia (AA) in
      children have been reported. The purpose of the authors' study was to describe
      oral lesions in children with AA. METHODS: The authors conducted a retrospective
      review using medical records of children diagnosed with AA who were treated at
      the Pediatric Service of the Regional Hospital of Concepcion, Chile, between
      March 1996 and May 2001. They recorded episodes of oral mucosal lesions and
      assessed platelet and neutrophil counts at the time the oral lesions appeared.
      RESULTS: Twelve children (nine boys and three girls) were diagnosed with AA.
      Their age range was 3 to 12 years (median age, 7 years). Nine subjects were
      receiving immunosuppressive therapy, and three received only supportive care. The
      most common oral manifestation of the disease was hemorrhage, which developed
      most often in patients with platelet counts less than 25 x 10(9) cells/liter. The
      second and third most common oral manifestations were candidiasis and viral
      infection, respectively. CONCLUSIONS: Children with AA frequently exhibit oral
      manifestations of the condition. Prevention, early diagnosis and proper treatment
      of oral complications are essential to diminish morbidity and avoid a possible
      fatal outcome. CLINICAL IMPLICATIONS: Oral lesions can be the first manifestation
      of AA; consequently, dentists should be aware of these manifestations so that an
      early diagnosis of the disease can be made.

PMID- 16637477
TI  - The use of COX-2 inhibitors for acute dental pain: A second look.
AB  - BACKGROUND: On the basis of their perceived better safety profile compared with
      other analgesic agents, cyclo-oxygenase-2 (COX-2) inhibitors have been prescribed
      frequently as first-line agents to treat acute dental pain. However, recently
      identified cardiovascular adverse reactions associated with these drugs mandate a
      reappraisal of their use in dental practice. TYPES OF STUDIES REVIEWED. The
      authors reviewed 18 clinical studies that evaluated the efficacy of a COX-2
      inhibitor for the treatment of acute dental pain. All of the studies used the
      widely established third-molar surgical extraction model to induce postsurgical
      inflammatory based pain, and all were randomized, double-blinded and placebo
      controlled. However, numerous vagaries in overall study design made direct
      comparisons difficult. RESULTS: None of the studies established any of the COX-2
      inhibitors as clearly better than ibuprofen, the current gold standard for the
      treatment of surgically induced dental pain. However, in single-dosing scenarios,
      the COX-2 inhibitor often demonstrated a longer duration of action compared with
      ibuprofen. CLINCAL IMPLICATIONS: The evidence to date fails to demonstrate any
      therapeutic advantage to using a COX-2 inhibitor to treat acute dental pain
      compared with ibuprofen. In the rare event that a COX-2 inhibitor may be
      appropriate, the clinician must inform the patient of the potential risks, and
      the drug should be used for the shortest possible time.

PMID- 16637478
TI  - Postural orthostatic tachycardia syndrome: Dental treatment considerations.
AB  - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a chronic,
      relatively common autonomic disorder typically affecting younger females. It is
      distinguished by a dramatic increase in heart rate on the assumption of an
      upright posture from the supine position. METHODS: The authors provide an
      overview of the demographics, clinical assessment, diagnostic features,
      differential diagnoses, pathogeneses and medical treatment of patients with POTS,
      with an emphasis on the clinical treatment of the dental patient affected by the
      syndrome. CONCLUSION: Patients frequently exhibit symptoms of lightheadedness,
      fatigue, palpitations and syncope. Patients with POTS may have Ehlers-Danlos
      syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the Brugada
      syndrome. Despite widespread dissemination of information regarding POTS in the
      medical literature, scant information on it has appeared in dental publications.
      PRACTICE IMPLICATIONS: Dentists need to be familiar with the clinical features of
      POTS and be prepared to treat patients at risk of developing syncope.

PMID- 16637479
TI  - Centric relation: A historical and contemporary orthodontic perspective.
AB  - BACKGROUND: Centric relation (CR) has been a controversial subject in dentistry
      for more than a century. For at least the past four decades, issues involving CR
      have been of interest to orthodontists. The definition of CR has changed over the
      past half-century from a retruded, posterior and, for the most part, superior
      condyle position to an anterior-superior condyle position. TYPE OF STUDIES
      REVIEWED: The authors addressed the historical and contemporary orthodontic
      perspective of CR. The source material for this review came mainly from
      literature and searches the lead author accumulated over the last 30 years. As
      there is no evidence-based (EB) model level 3 (systemic) review on the topic of
      CR, the best evidence on this subject was gleaned only from a thorough
      examination and evaluation at EB model level 2 (experience plus best available
      sample studies). There was, however, enough high-quality EB model level 2
      information on the topic of CR for the authors to draw conclusions on the basis
      of a scientific appraisal of relevant research. RESULTS: Although the reliability
      of CR records has been substantiated, the records' validity has little to no
      evidentiary support. In addition, population-based sample studies and consensus
      statements from national conferences support the view that the positions of the
      temporomandibular joint (TMJ) condyles in relation to the glenoid fossa or CR
      position are not diagnostic of temporomandiblar disorders. There appears to be
      little to no benefit of using gnathologic records and articulator-mounted dental
      casts to discern discrepancies in maximum intercuspation of the teeth coincident
      with TMJ condyles in an anterior-superior CR position in orthodontic patients.
      CLINICAL IMPLICATIONS: The benefit of using gnathologic CR records and
      articulators in orthodontics has not been substantiated by scientific evidence.

PMID- 16637480
TI  - Balancing efficacy and safety in the use of oral sedation in dental outpatients.
AB  - BACKGROUND: Concerns about the safety of pediatric oral sedation and the
      incremental use of triazolam in adults prompted a workshop cosponsored by several
      professional organizations. OVERVIEW: There is a strong need and demand for adult
      and pediatric sedation services. Using oral medication to achieve anxiolysis in
      adults appears to have a wide margin of safety. Mortality and serious morbidity,
      however, have been reported with oral conscious sedation, especially in young
      children. Most serious adverse events are related to potentially avoidable
      respiratory complications. CONCLUSIONS: Clinical trials are needed to evaluate
      oral sedative drugs and combinations, as well as to develop discharge criteria
      with objective quantifiable measures of home readiness. Courses devoted to airway
      management should be developed for dentists who provide conscious sedation
      services. State regulation of enteral administration of sedatives to achieve
      conscious sedation is needed to ensure safety. PRACTICE IMPLICATIONS: Safety in
      outpatient sedation is of paramount concern, with enteral administration of
      benzodiazepines appearing safe but poorly documented in the office setting.
      Conscious sedation by the enteral route, including incremental triazolam,
      necessitates careful patient evaluation, monitoring, documentation, facilities,
      equipment and personnel as described in American Dental Association and American
      Academy of Pediatric Dentistry guidelines.

PMID- 16637481
TI  - Fracture resistance of different partial-coverage ceramic molar restorations: An
      in vitro investigation.
AB  - BACKGROUND: The authors conducted a study to evaluate the influence of
      preparation design on reliability and fracture resistance of press-ceramic
      posterior partial-coverage restorations (PCRs) under fatigue. They compared the
      results for PCRs fabricated of a new press ceramic (IPS e.max Press-VP 1989/4,
      Ivoclar-Vivadent, Schaan, Liechtenstein) with results for ceramic inlays and
      unprepared molars. METHODS: The authors randomly divided 96 human upper molars
      into six equal groups. Control group NP specimens remained unprepared. Control
      group IN specimens received a mesio-occlusal-distal (MOD) inlay preparation. The
      test groups received PCR preparation designs based on group IN's inlay design,
      with additional cuspal reduction that increased from group to group. The authors
      fabricated 16 ceramic inlays and 64 PCRs of IPS e.max Press and luted them
      adhesively. All specimens underwent masticatory fatigue loading (1.2 million
      cycles, 1.6 hertz, 98 newtons), 5,300 thermal cycles and observation for fracture
      patterns. Afterward, the authors loaded all surviving specimens until fracture.
      RESULTS: No fractures occurred during the exposure to the masticatory simulation.
      After undergoing loading in a universal testing machine, the groups showed no
      significant differences in fracture strength values (P = .6026). Thus, the
      different preparation designs of the PCRs demonstrated no significant influence
      on the restorations' fracture resistance. The median failure loads ranged from
      1,567 to 1,960 newtons. CONCLUSION: All-ceramic PCRs for molars made of IPS e.max
      Press were shown to be fracture-resistant, results comparable with those of
      natural unprepared teeth. CLINICAL IMPLICATIONS: When a posterior ceramic PCR is
      indicated, the clinician should perform a defect-oriented preparation that
      preserves tooth structure. Further clinical investigations are recommended to
      verify the authors' in vitro results.

PMID- 16637482
TI  - Reports to the National Practitioner Data Bank involving dentists, 1990-2004.
AB  - BACKGROUND: While the National Practitioner Data Bank (NPDB) contains reports
      relating to dentists, an analysis of these data has not been published. METHODS:
      The authors analyze 47,441 reports to the NPDB relating to malpractice payments,
      licensure actions and adverse actions against dentists from Sept. 1, 1990, to
      Sept. 30, 2004. RESULTS: A total of 13.2 percent of all NPDB reports were related
      to dentists. Of these, 73.7 percent resulted from malpractice actions and the
      remaining 26.3 percent were from adverse actions. While the number of large
      payments increased over this period, the median payment remained relatively
      stable. CONCLUSIONS: Dental malpractice settlements and judgments generally have
      kept pace with inflation over the past decade. PRACTICE IMPLICATIONS: Dentists
      should be aware that the NPDB retains reports of adverse actions and malpractice
      settlements and judgments indefinitely. These reports are available to hospitals
      evaluating their credentials, state licensing boards and certain health care
      entities (for example, health maintenance organizations and preferred provider
      organizations) entering into an employment or other relationship with them.

PMID- 16637483
TI  - The 'new' operative dentistry.
AB  - During the past few decades, life expectancy has increased significantly. As a
      result, mature patients often have receding gingival tissues, physical and mental
      debilitation, less energy and motivation, and the resultant Class V carious
      lesions. In this article, I suggest the use of high-level fluoride in
      toothpastes, remineralizing pastes and high-level fluoride gels for topical
      application in trays to reduce the progression of caries. To accompany fluoride
      therapy, high-fluoride-releasing restorative materials are indicated for Class V
      carious lesions. Adequate caries-preventive and restorative concepts for mature
      patients require planning, patient education and close patient supervision.

PMID- 16637484
TI  - Practice transitions and risk management considerations.

PMID- 16637485
TI  - Are MSOs and orthodontists partners?

PMID- 16637486
TI  - What may I advertise after completing courses that I have taken to expand my
      practice and patient treatment?

PMID- 16637487
TI  - For the dental patient...healthy mouth, healthy body.

PMID- 16637488
TI  - Adaptive change in the resource-exploitation traits of a generalist consumer: the
      evolution and coexistence of generalists and specialists.
AB  - Mathematical models of consumer-resource systems are used to explore the
      evolution of traits related to resource acquisition in a generalist consumer
      species that is capable of exploiting two resources. The analysis focuses on
      whether evolution of traits determining the capture rates of two resources by a
      consumer species produce one generalist, two specialists, or all three types,
      when all types are characterized by a common fitness function. In systems with a
      stable equilibrium, evolution produces one generalist or two specialists,
      depending on the second derivative of the trade-off relationship. When there are
      sustained population fluctuations, the nature of the trade-off between the
      consumer's capture rates of the two resources still plays a key role in
      determining the evolutionary outcome. If the trade-off is described by a choice
      variable between zero and one that is raised to a power n, polymorphic states are
      possible when n > 1, which implies a positive second derivative of the curve.
      These states are either dimorphism, with two relatively specialized consumer
      types, or trimorphism, with a single generalist type and two specialists. Both
      endogenously driven consumer-resource cycles, and fluctuations driven by an
      environmental variable affecting resource growth are considered. Trimorphic
      evolutionary outcomes are relatively common in the case of endogenous cycles. In
      contrast to a previous study, these trimorphisms can often evolve even when new
      lineages are constrained to have phenotypes very similar to existing lineages.
      Exogenous cycles driven by environmental variation in resource growth rates
      appear to be much less likely to produce a mixture of generalists and specialists
      than are endogenous consumer-resource cycles.

PMID- 16637489
TI  - Self-imposed silence: parental antagonism and the evolution of X-chromosome
      inactivation.
AB  - A model is proposed for the evolution of X-chromosome inactivation (XCI) in which
      natural selection initially favors the silencing of paternally derived alleles of
      X-linked demand inhibitors. The compensatory upregulation of maternally derived
      alleles establishes a requirement for monoallelic expression in females. For this
      reason, XCI is self-reinforcing once established. However, inactivation of a
      particular X chromosome is not. Random XCI (rXCI) is favored over paternal XCI
      because rXCI reduces the costs of functional hemizygosity in females. Once
      present, rXCI favors the evolution of locus-by-locus imprinting of X-linked loci,
      which creates an evolutionary dynamic in which different chromosomes compete to
      remain active.

PMID- 16637490
TI  - Stochasticity, complex spatial structure, and the feasibility of the shifting
      balance theory.
AB  - Sewall Wright's shifting balance theory of evolution posits a mechanism by which
      a structured population may escape local fitness optima and find a global
      optimum. We examine a one-locus, two-allele model of underdominance in
      populations with differing spatial arrangements of demes, both analytically and
      with Monte Carlo simulations. We find that inclusion of variance in interpatch
      connectivities can significantly reduce the number of generations required for
      fixation of the more favorable allele relative to island and stepping-stone
      models. Although time to fixation increases with migration rate in all cases, the
      presence of one or two relatively isolated demes may reduce the number of
      generations by 80% or more. These results suggest that the shifting balance
      process may operate under less restrictive conditions than those found with a
      simple spatial arrangement of demes.

PMID- 16637491
TI  - Nonparametric estimation of natural selection on a quantitative trait using mark
      recapture data.
AB  - Assessing natural selection on a phenotypic trait in wild populations is of
      primary importance for evolutionary ecologists. To cope with the imperfect
      detection of individuals inherent to monitoring in the wild, we develop a
      nonparametric method for evaluating the form of natural selection on a
      quantitative trait using mark-recapture data. Our approach uses penalized splines
      to achieve flexibility in exploring the form of natural selection by avoiding the
      need to specify an a priori parametric function. If needed, it can help in
      suggesting a new parametric model. We employ Markov chain Monte Carlo sampling in
      a Bayesian framework to estimate model parameters. We illustrate our approach
      using data for a wild population of sociable weavers (Philetairus socius) to
      investigate survival in relation to body mass. In agreement with previous
      parametric analyses, we found that lighter individuals showed a reduction in
      survival. However, the survival function was not symmetric, indicating that body
      mass might not be under stabilizing selection as suggested previously.

PMID- 16637492
TI  - When not to avoid inbreeding.
AB  - Avoidance of incestuous matings is widely reported across many animal taxa, and
      the adaptive value of such behavior is explained through inbreeding depression.
      However, an old and somewhat neglected theoretical result predicts that inbred
      matings offer another, positive effect on the inclusive fitness of parents: an
      individual who mates with a relative will help that relative to spread genes
      identical by descent. This benefit can be substantial, if the additional mating
      achieved by the relative does not harm his mating success otherwise, and in the
      context of selfing in plants the phenomenon is well known. Here, we develop a
      model that derives expected values of inbreeding tolerance, that is, the
      magnitude of inbreeding depression that is required to make individuals avoid
      inbreeding, for different animal life histories and parental investment patterns.
      We also distinguish between simultaneous and sequential mate choice, and show
      that inbreeding tolerance should often be remarkably high in the latter scenario
      in particular, although egalitarian parental care will lead to lower tolerance.
      There is a mismatch between theory and data: the almost complete lack of cases
      where individuals prefer to mate incestuously is at odds with a large overlap
      between the predicted range of inbreeding tolerance and estimates of inbreeding
      depression found in nature. We discuss four different solutions to this enigma,
      and suggest that inbreeding tolerance, where it is found, should not always be
      attributed to a simple constraint that has prevented finding any other mate.

PMID- 16637493
TI  - Neutral theory, phylogenies, and the relationship between phenotypic change and
      evolutionary rates.
AB  - The neutral theory of molecular evolution predicts that rates of phenotypic
      change are largely independent from genotypic change. A recent study by Bromham
      et al. (2002) confirmed this expectation, finding no evidence for correlated
      phenotypic and molecular evolutionary rates in animals. We reevaluate this
      hypothesis, sampling at different taxonomic levels in plants and animals, using
      Bayesian inference to reconstruct phylogenetic trees and estimate rates of
      molecular evolution. We use independent contrasts in branch lengths to maximize
      the information extracted from each of the trees and nodal posterior
      probabilities to assess the influence of phylogenetic error. Our results indicate
      that in vascular plants between 2% and 11% of the variation in phenotypic rates
      of change can be explained by the rate of genotypic change. These results may be
      explained by the idea that processes that affect general evolutionary rates, such
      as body size, may also be expected to influence rates of morphological change.

PMID- 16637494
TI  - The dynamics of diversification in evolving Pseudomonas populations.
AB  - Determining the mechanisms that promote the evolution of diversity is a central
      problem in evolutionary biology. Previous studies have demonstrated that
      diversification occurs in complex environments and that genotypes specialized on
      alternative resources can be maintained over short time scales. Here, we describe
      a selection experiment that has tracked the dynamics of adaptive diversification
      within selection lines of the asexual bacteria Pseudomonas fluorescens over about
      900 generations. We cultured experimental populations from the same two isogenic
      ancestral strains in simple, single-substrate environments or in complex, four
      substrate environments. Following selection we assayed the growth of genotypes
      from each population on each substrate individually. We estimated mutational
      heritability, Vm/VE, as 1 x 10(-3) per generation in simple environments and 3 x
      10(-3) per generation in complex environments. These values are roughly
      consistent with estimates reported in other systems. Populations selected in
      complex environments evolved into genetically diverse communities. Genotypes
      exhibited greater metabolic differentiation from other genotypes in their own
      population than to genotypes evolving in other populations, presumably as a
      result of resource competition. In populations selected in simple environments,
      little genetic diversity evolved, and genotypes shared very similar phenotypes.
      Our findings suggest that ecological opportunity provided by environmental
      complexity plays a major role in the evolution and maintenance of diversity.

PMID- 16637495
TI  - The genetic basis of floral traits associated with mating system evolution in
      Leptosiphon (Polemoniaceae): an analysis of quantitative trait loci.
AB  - Mapping of quantitative trait loci (QTL) was used to investigate the genetic
      architecture of divergence in floral characters associated with the mating
      system, an important adaptive trait in angiosperms. Two species of Leptosiphon
      (Polemoniaceae), one strongly self-fertilizing (L. bicolor) and the other
      partially outcrossing (L. jepsonii), were crossed to produce F2 and both
      backcross progenies. For each crossing population, a linkage map was created
      using amplified fragment length polymorphism markers, and QTL were identified for
      several dimensions of floral size. For each of the five traits examined, three to
      seven QTL were detected, with independent datasets yielding congruent results in
      some but not all cases. The phenotypic effect of individual QTL was generally
      moderate. We estimated that many of the QTL were additive or showed dominance
      toward L. bicolor, whereas comparison of mean trait values for parental and cross
      progenies showed apparent overall dominance of L. jepsonii traits. Colocalization
      of QTL for different dimensions of floral size was consistent with high
      phenotypic correlations between floral traits. Substantial segregation distortion
      was observed in marker loci, the majority favoring alleles from the large
      flowered parent. A low frequency of male sterility in the F2 population is
      consistent with the Dobzhansky-Muller model for the evolution of reproductive
      isolation.

PMID- 16637496
TI  - Cryptic interspecific introgression and genetic differentiation within Gossypium
      aridum (Malvaceae) and its relatives.
AB  - Interspecific gene flow is increasingly recognized as an important evolutionary
      phenomenon in plants. A surprising observation is that historical introgression
      is often inferred between species that presently have geographic and reproductive
      barriers that would appear to prohibit the inferred sexual exchange. A striking
      example concerns Gossypium aridum (subsection Erioxylum); previous analyses have
      shown that populations from Colima (southwestern Mexico) have a chloroplast
      genome (cpDNA) similar to that of a different taxonomic subsection (Integrifolia)
      that presently is confined to Baja California and the Galapagos Islands, whereas
      other G. aridum populations share a cpDNA lineage with each other and with other
      species in subsection Erioxylum. To evaluate further the possibility that this
      cpDNA evidence reflects introgression as opposed to some other evolutionary
      process, as well as to explore patterns of genetic diversity and similarity in
      both subsections, we conducted amplified fragment-length polymorphism (AFLP)
      analysis using 50 populations representing all seven species in the two
      subsections. Genetic diversity is high in G. aridum, and is strongly correlated
      with geography, as are similarities among the five species in subsection
      Erioxylum. This subsection is genetically distant from the two species in
      subsection Integrifolia, whose populations are highly similar inter se.
      Populations of G. aridum from Colima are genetically distinct from the remainder
      of the species, and exhibit a comparatively high frequency of AFLP fragments that
      otherwise are diagnostic of the Integrifolia lineage. These data implicate
      intersubsectional introgression between presently allopatric and genetically
      isolated clades, giving rise to a morphologically cryptic, introgressant entity.
      Biogeographic considerations suggest that this history was initiated following
      migration of one or more seeds from Baja California to the Colima coast, perhaps
      during the Pleistocene. We suggest that cryptic and seemingly improbable
      interspecific introgression and molecular differentiation may be more common than
      appreciated in angiosperm evolution.

PMID- 16637497
TI  - Comparative analyses of population structure in two subspecies of Nigella
      degenii: evidence for diversifying selection on pollen-color dimorphisms.
AB  - Flower color can be a major determinant of plant fitness, not only because of
      preferential visitation by pollinators but also because of pleiotropic
      relationships between the expression of floral pigments and biochemically related
      compounds that influence vegetative performance variables. Different environments
      may therefore favor different pigmentation phenotypes. We examined whether
      spatially varying selection has played a major role in shaping large-scale
      patterns of differentiation in two subspecies of Nigella degenii (Ranunculaceae),
      with particular emphasis on pollen color. The two subspecies appear to have been
      genetically isolated for substantial periods of time and, therefore, provide a
      "replicated test" for the effect of natural selection. Estimates of population
      structure based on a suite of floral and vegetative characters were compared with
      the corresponding data for amplified fragment length polymorphism (AFLP) markers,
      which were assumed to be selectively neutral. We found low levels of genetic
      structure within the subspecies using both the AFLP markers (FST < or = 0.05) and
      quantitative characters (QST < or = 0.15), with no statistically significant
      differences between the two measures. There is, therefore, no evidence of
      diversifying selection being important in structuring variation in quantitative
      characters within each of the two subspecies. In contrast, estimates of
      differentiation in pollen color (FST > or = 0.10) significantly exceeded the
      neutral expectations (estimated from AFLP data), suggesting that local adaptation
      has played a key role in the evolution of this monogenic character.

PMID- 16637498
TI  - Inbreeding avoidance and the evolution of gender dimorphism in Wurmbea
      biglandulosa (Colchicaceae).
AB  - How females establish in populations of cosexuals is central to understanding the
      evolution of gender dimorphism in angiosperms. Inbreeding avoidance hypotheses
      propose that females can establish and be maintained if cosexual fitness is
      reduced because they self-fertilize, and their progeny express inbreeding
      depression. Here we assess the role of inbreeding avoidance in maintaining sexual
      system variation in Wurmbea biglandulosa. We estimated costs of self-pollination,
      mating patterns, and inbreeding depression in gender monomorphic (cosexuals only)
      and dimorphic (males and females) populations. Costs of selfing, estimated from
      seed set of experimentally self- and cross-pollinated flowers, were severe in
      both males and cosexuals (inbreeding depression, sigma = 0.86). In a field
      experiment, intact males that could self produced fewer seeds than both
      emasculated males and females, whereas seed set of intact and emasculated
      cosexuals did not differ. Thus, pollinator-mediated selfing reduces fitness of
      males but not cosexuals under natural conditions. Outcrossing rates of males
      revealed substantial selfing (t = 0.68), whereas females and cosexuals were
      outcrossed (0.92 and 0.97). For males, progeny inbreeding coefficients exceeded
      parental coefficients (0.220 vs. 0.009), whereas for females and cosexuals these
      coefficients did not differ and approached zero. Differences in coefficients
      between males and their progeny indicate that selfed progeny express severe
      inbreeding depression (sigma = 0.93). Combined with inbreeding depression for
      seed set, cumulative sigma = 0.99, indicating that most or all selfed zygotes
      fail to reach reproductive maturity. We propose that present sexual system
      variation in W. biglandulosa is maintained by high inbreeding depression coupled
      with differences in selfing rates among monomorphic and dimorphic populations.

PMID- 16637499
TI  - Reproductive isolation between two closely related hummingbird-pollinated
      neotropical gingers.
AB  - Empirical estimates of the relative importance of different barriers to gene flow
      between recently diverged species are important for understanding processes of
      speciation. I investigated the factors contributing to reproductive isolation
      between Costus pulverulentus and C. scaber (Costaceae), two closely related
      hummingbird-pollinated understory Neotropical herbs. I studied broad-scale
      geographic isolation, microhabitat isolation, flowering phenology, overlap in
      pollinator assemblages, floral constancy by pollinators, mechanical floral
      isolation, pollen-pistil interactions, seed set in interspecific crosses, and
      postzygotic isolation (hybrid seed germination, greenhouse survival to flowering,
      and pollen fertility). Aside from substantial geographic isolation, I found
      evidence for several factors contributing to reproductive isolation in the
      sympatric portion of their geographic ranges, but the identity and relative
      strength of these factors varied depending on the direction of potential gene
      flow. For C. pulverulentus as the maternal parent, mechanical floral isolation
      was the most important factor, acting as a complete block to interspecific pollen
      deposition. For C. scaber as the maternal parent, microhabitat isolation,
      pollinator assemblage, mechanical floral isolation, and postpollination pollen
      pistil incompatibility were important. Overall, prezygotic barriers were found to
      be strong, resulting in 100% reproductive isolation for C. pulverulentus as the
      maternal parent and 99.0% reproductive isolation for C. scaber as the maternal
      parent. Some postzygotic isolation also was identified in the F1 generation,
      increasing total isolation for C. scaber to 99.4%. The results suggest that
      ecological factors, including habitat use and plant-pollinator interactions,
      contributed to speciation in this system and evolved before extensive intrinsic
      postzygotic isolation.

PMID- 16637500
TI  - Minimal selfing, few clones, and no among-host genetic structure in a
      hermaphroditic parasite with asexual larval propagation.
AB  - Little is known about actual mating systems in natural populations of parasites
      or about what constitutes the limits of a parasite deme. These parameters are
      interesting because they affect levels of genetic diversity, opportunities for
      local adaptation, and other evolutionary processes. We expect that transmission
      dynamics and the distribution of parasites among hosts should have a large effect
      on mating systems and demic structure, but currently we have mostly speculation
      and very few data. For example, infrapopulations (all the parasites in a single
      host) should behave as demes if parasite offspring are transmitted as a clump
      from host to host over several generations. However, if offspring are well mixed,
      then the parasite component population (all the parasites among a host
      population) would function as the deme. Similarly, low mean intensities or a high
      proportion of worms in single infections should increase the selfing rate. For
      species having an asexual amplification stage, transmission between intermediate
      and definitive (final) hosts will control the variance in clonal reproductive
      success, which in turn could have a large influence on effective sizes and rates
      of inbreeding. We examined demic structure, selfing rates, and the variance in
      clonal reproductive success in natural populations of Plagioporus shawi, a
      hermaphroditic trematode that parasitizes salmon. Overall levels of genetic
      diversity were very high. An a posteriori inference of population structure
      overwhelmingly supports the component population as the deme, rather than
      individual infrapopulations. Only a single pair of 597 adult individuals was
      identified as clones. Thus, the variance in clonal reproductive success was
      almost zero. Despite being hermaphroditic, P. shawi appears to be almost entirely
      outcrossing. Genetic estimates of selfing (<5%) were in accordance with the
      proportion of parasites from single infections. Thus, it appears that individual
      flukes outcross whenever possible and only resort to selfing when alone. Finally,
      our data support the hypothesis that aquatic transmission and the use of several
      intermediate hosts promotes high genetic diversity and well-mixed
      infrapopulations.

PMID- 16637501
TI  - Quantitative genetics of plastron shape in slider turtles (Trachemys scripta).
AB  - Shape variation is widespread in nature and embodies both a response to and a
      source for evolution and natural selection. To detect patterns of shape
      evolution, one must assess the quantitative genetic underpinnings of shape
      variation as well as the selective environment that the organisms have
      experienced. Here we used geometric morphometrics to assess variation in plastron
      shell shape in 1314 neonatal slider turtles (Trachemys scripta) from 162 clutches
      of laboratory-incubated eggs from two nesting areas. Multivariate analysis of
      variance indicated that nesting area has a limited role in describing plastron
      shape variation among clutches, whereas differences between individual clutches
      were highly significant, suggesting a prominent clutch effect. The covariation
      between plastron shape and several possible maternal effect variables (yolk
      hormone levels and egg dimensions) was assessed for a subset of clutches and
      found to be negligible. We subsequently employed several recently proposed
      methods for estimating heritability from shape variables, and generalized a
      univariate approach to accommodate unequal sample sizes. Univariate estimates of
      shape heritability based on Procrustes distances yielded large values for both
      nesting populations (h2 approximately 0.86), and multivariate estimates of
      maximal additive heritability were also large for both nesting populations (h2max
      approximately 0.57). We also estimated the dominant trend in heritable shape
      change for each nesting population and found that the direction of shape
      evolution was not the same for the two sites. Therefore, although the magnitude
      of shape evolution was similar between nesting populations, the manner in which
      plastron shape is evolving is not. We conclude that the univariate approach for
      assessing quantitative genetic parameters from geometric morphometric data has
      limited utility, because it is unable to accurately describe how shape is
      evolving.

PMID- 16637503
TI  - Hybridization of Bombina bombina and B. variegata (Anura, Discoglossidae) at a
      sharp ecotone in western Ukraine: comparisons across transects and over time.
AB  - Bombina bombina and B. variegata are two anciently diverged toad taxa that have
      adapted to different breeding habitats yet hybridize freely in zones of overlap
      where their parapatric distributions meet. Here, we report on a joint genetic and
      ecological analysis of a hybrid zone in the vicinity of Stryi in western Ukraine.
      We used five unlinked allozyme loci, two nuclear single nucleotide polymorphisms
      and a mitochondrial DNA haplotype as genetic markers. Parallel allele frequency
      clines with a sharp central step occur across a sharp ecotone, where transitions
      in aquatic habitat, elevation, and terrestrial vegetation coincide. The width of
      the hybrid zone, estimated as the inverse of the maximum gradient in allele
      frequency, is 2.3 km. This is the smallest of four estimates derived from
      different clinal transects across Europe. We argue that the narrow cline near
      Stryi is mainly due to a combination of habitat distribution and habitat
      preference. Adult toads show a preference for either ponds (B. bombina) or
      puddles (B. variegata), which is known to affect the distribution of genotypes
      within the hybrid zones. At Stryi, it should cause a reduction of the dispersal
      rate across the ecotone and thus narrow the cline. A detailed comparison of all
      five intensively studied Bombina transects lends support to the hypothesis that
      habitat distribution plus habitat preference can jointly affect the structure of
      hybrid zones and, ultimately, the resulting barriers to gene flow between
      differentiated gene pools. This study also represents a resampling of an area
      that was last studied more than 70 years ago. Our allele-frequency clines largely
      coincide with those that were described then on the basis of morphological
      variation. However, we found asymmetrical introgression of B. variegata genes
      into B. bombina territory along the bank of a river.

PMID- 16637502
TI  - A multilocus perspective on refugial isolation and divergence in rainforest
      skinks (Carlia).
AB  - To explore the evolutionary consequences of climate-induced fluctuations in
      distribution of rainforest habitat we contrasted demographic histories of
      divergence among three lineages of Australian rainforest endemic skinks. The red
      throated rainbow skink, Carlia rubrigularis, consists of morphologically
      indistinguishable northern and southern mitochondrial DNA (mtDNA) lineages that
      are partially reproductively isolated at their parapatric boundary. The third
      lineage (C. rhomboidalis) inhabits rainforests just to the south of C.
      rubrigularis, has blue, rather than red-throated males, and for mtDNA is more
      closely related to southern C. rubrigularis than is northern C. rubrigularis.
      Multigene coalescent analyses supported more recent divergence between
      morphologically distinct lineages than between morphologically conservative
      lineages. There was effectively no migration and therefore stronger isolation
      between southern C. rubrigularis and C. rhomboidalis, and low unidirectional
      migration between morphologically conservative lineages of C. rubrigularis. We
      found little or no evidence for strong differences in effective population size,
      and hence different contributions of genetic drift in the demographic history of
      the three lineages. Overall the results suggest contrasting responses to long
      term fluctuations in rainforest habitats, leading to varying opportunities for
      speciation.

PMID- 16637504
TI  - The geography of mammalian speciation: mixed signals from phylogenies and range
      maps.
AB  - The importance of geographic isolation in speciation has been debated since the
      19th century. Since the beginning of the 20th century, the consensus has been
      that most speciation involves divergence in allopatry. This consensus was based
      largely on decades of observations by naturalists and verbal arguments against
      speciation without isolation. Recent attempts to quantify the importance of
      allopatric versus sympatric speciation using comparative methods called "age
      range correlation" (ARC) suggest that allopatric speciation is more common than
      sympatric speciation. However, very few taxa have been studied and there are
      concerns about the adequacy of the methods. We propose methodological
      improvements including changes in the way overlap between clades is quantified
      and Monte Carlo methods to test the null hypothesis of no relationship between
      phylogenetic relatedness and geographic range overlap. We analyze 14 clades of
      mammals, chosen because of the availability of data and the consensus among
      mammalogists that speciation is routinely allopatric. Although data from a few
      clades clearly indicate allopatric speciation, divergence with gene flow is
      plausible in others and many results are inconclusive. The relative rarity of
      significant correlations between phylogenetic distance and range overlap may have
      three distinct causes: (1) post-speciation range changes, (2) relative rarity of
      range overlap, and (3) a mixture of geographic modes of speciation. Our results
      support skepticism about ARC's power for inferring the biogeography of
      speciation. Yet, even if few clades provide clear signals, meta-analytic
      approaches such as ARC may set bounds on the prevalence of alternative modes of
      speciation.

PMID- 16637505
TI  - Multiple infections: relatedness and time between infections affect the
      establishment and growth of the cestode Schistocephalus solidus in its
      stickleback host.
AB  - We studied experimental double infections of the cestode Schistocephalus solidus
      in its stickleback host. In particular, we were interested in how two important
      components of the cestode's transmission success-establishment and growth within
      the fish host-were affected by the relatedness of the two parasites in a double
      exposure and by the timing of the two exposures, that is, whether they occurred
      simultaneously or sequentially. We found that male sticklebacks more often became
      infected (singly or doubly) if the two cestodes in the exposures were related,
      whereas female sticklebacks were more easily infected (singly or doubly) when
      exposed to two unrelated cestodes. Irrespective of the fish's gender, successful
      infections more often contained both cestodes when they were related. In
      sequential exposures with related as well as unrelated cestodes, the cestode in
      the later exposure survived better and also grew larger than the cestode from the
      first exposure, despite being one week younger. Our results emphasize that within
      host dynamics and factors acting at this level can play an important role in
      determining a parasite's transmission success.

PMID- 16637506
TI  - Proper control of genetic background with precise allele substitution: a comment
      on Coyne and Elwyn.
AB  - Coyne and Elwyn report that, using Drosophila stocks provided by us, they were
      unable to replicate our experiments measuring the effects of desaturase-2 on
      stress tolerance. In this note, we provide evidence that these authors did not
      properly control for the differences in genetic background between the lines.
      Their experiments are thus not meaningful replications of our previous ones. We
      discuss ways of circumventing this problem in studies involving induced mutations
      in single genes.

PMID- 16637508
TI  - Epidermal growth factor receptor: a promising therapeutic target for colorectal
      cancer.
AB  - The epidermal growth factor receptor is a 170,000-kd transmembrane glycoprotein
      involved in signaling pathways affecting cellular growth, differentiation, and
      proliferation. An abnormal expression of the epidermal growth factor receptor
      (EGFR) has been described in many human tumors and implicated in the development
      and prognosis of malignancies, thus representing not only a possible prognostic
      marker, but primarily a rational molecular target for a new class of anticancer
      agents. The aim of this analysis is to review the available data about the
      biology of the EGFR and its use as a target for a new class of anticancer agents
      for colorectal cancer. Several clinical trials have been reported with the use of
      EGFR-targeted monoclonal antibodies and tyrosine kinase inhibitors, mainly in
      combination with chemotherapy for advanced colorectal cancer patients. Results
      available so far demonstrated a manageable and acceptable toxicity profile and a
      promising level of activity. Many critical issues are yet unresolved, such as the
      optimal chemotherapy regimen to combine with anti-EGFR treatment and the most
      adequate patient setting. Moreover, the biological selection of colorectal tumors
      more likely to benefit from this treatment approach is still to be defined.

PMID- 16637509
TI  - Application of different methods for nuclear shape analysis with special
      reference to the differentiation of brain tumors.
AB  - OBJECTIVE: To study the discriminatory power of different methods designed for
      nuclear shape analysis with reference to the differentiation and grading of brain
      tumors and the differentiation between proliferating and nonproliferating nuclei.
      STUDY DESIGN: At least 300 tumor cell nuclei per case were measured by means of a
      digital image analysis system. Fourier amplitudes no. 1 to 15, moments no. 1 to 7
      according to Hu, roundness factor, ellipse shape factor, concavity factor, Feret
      ratio, fractal dimension and bending energy were determined for each nucleus. The
      discriminatory power of these parameters was tested in three pairwise
      comparisons: (1) oligodendrogliomas WHO grade II (n = 13) vs. grade III (n = 11),
      (2) medulloblastomas WHO grade IV (n = 14) vs. anaplastic ependymomas WHO grade
      III (n = 12), (3) Ki-67-positive vs. Ki-67-negative tumor cell nuclei in the 14
      medulloblastomas. RESULTS: When data from Fourier analysis were included in
      statistical analysis, cross-validated discriminant analysis led to a 100% correct
      reclassification for the first and for the second pairwise comparison and to a
      75% correct reclassification when comparing Ki-67-positive and Ki-67-negative
      nucleifrom medulloblastomas. Different combinations of the other shape parameters
      led to a lower percentage of correctly reclassified cases for all three pairwise
      comparisons, especially when Fourier analysis was not included in the analysis.
      CONCLUSION: Fourier analysis provided an optimal statistical discrimination
      between different brain tumor entities and between data sets from proliferating
      and nonproliferating tumor cell nuclei. Since nuclear shape is an important
      criterion for the investigation of tumors, the application of Fourier analysis is
      therefore recommended for quantitative histologic investigations in neuro
      oncology.

PMID- 16637510
TI  - Optimized quality of histologic images allows the use of neural network scanning
      in diagnosis of fungal infection of abnormal nails.
AB  - OBJECTIVE: The neural network scanning (NNS) system, formerly known as Papnet, is
      capable of selecting fungi in cervical smears. The objective of this study was to
      investigate whether the optimized quality of histologic images created using a
      combination of coagulant fixation and microwave histoprocessing allows the
      application of this computer-assisted microscopy in the diagnostic process. STUDY
      DESIGN: In a prospective study, 117 abnormal nails clinically suspect for fungal
      disease werefixed in a coagulant fixative, BoonFix, processed in a microwave
      histoprocessor to obtain optimal paraffin sections and stained with the periodic
      acid-Schiff (PAS) method. The stained paraffin sections were randomly numbered
      and screened by two independent pathologists for diagnosis of fungal hyphae and
      spores. The same sections were subsequently scanned by a neural network, and a
      maximum of 128 digital images produced by the system were screened and diagnosed
      by pathologists. Using light microscopy as the gold standard for diagnosis of
      fungi, the usefulness of NNS was then assessed. RESULTS: The fungi and spores
      were clearly demonstrated in the paraffin sections, and the NNS system detected
      and recorded them efficiently. The hyphae and spores could be identified in these
      pixilated images with relative ease. Of the 117 examined cases, 50 were positive
      and 47 negative by both methods. In the 20 remaining cases, NNS did not present
      images of fungi that were present in the histologic sections. In practice, this
      implies that only 67 out of 117 cases (57%) must be screened by light microscopy.
      NNS recorded not only fungi and spores in the 128 digital images but also
      artifacts, such as round, deeply PAS-positive granules of talcum powder, which by
      light microscopy might be mistaken for fungal spores. CONCLUSION: NNS proves
      applicable for the selection of spores and fungi if the histologic sections are
      of sufficiently high quality. As a result, the number of slides to be screened by
      light microscopy can be reduced substantially. In a throughput diagnostic
      laboratory handling a large number of such cases this technology can be highly
      valuable.

PMID- 16637511
TI  - Endometrial and endocervical secretion: the search for histochemical
      differentiation.
AB  - OBJECTIVE: To determine the ideal histochemical stain to differentiate between
      non-neoplastic and neoplastic endocervix and endometrium. STUDY DESIGN: A total
      of 90 cases representing nonneoplastic cervix, non-neoplastic endometrium,
      endocervical adenocarcinoma and endometrial adenocarcinoma were stained with
      toluidine blue (TB); methylene blue (MB); mucicarmine (MUC); periodic acid-Schiff
      before and after diastase digestion (PAS, PAS-D); Alcian blue, pH 2.5 (AB); and
      periodic acid-Schiff after Alcian blue, pH 2.5 (PAB). Cases were blinded and
      randomly divided between two pathologists for evaluation of the staining and the
      staining distribution of the glandular epithelium by means of a 36-color scheme.
      RESULTS: The majority of non-neoplastic endocervix samples stained blue with MB
      (57%), fuchsia with MUC (70%), magenta with PAS (77%) and PAS-D (73%) and dark
      turquoise with AB (70%). The majority of non-neoplastic endometrium samples
      stained slate blue with TB (60%) and pink with PAS-D (53.3%). There is
      statistical difference (p < 0.05) in the color of the epithelium and secretions
      between the non-neoplastic cervix and endometrium. The malignant glands of
      endocervical origin could be differentiated significantly (p = 0.043) from non
      neoplastic endocervical epithelium by MUC. The epithelium of the non-neoplastic
      endometrium is significantly differentiated from malignant endometrium using TB
      (p = 0.015) and MB (p = 0.038). Endocervical carcinoma could be significantly
      differentiated from endometrial carcinoma by MB. The staining in endocervical
      adenocarcinoma and endometrial carcinoma was predominantly present in both apical
      and cytoplasmic locations compared to their non-neoplastic counterparts
      (endocervix, p = 0.003; endometrium, p = 0.049). CONCLUSION: This study showed
      that a panel of histochemical stains could differentiate glandular cells of
      endocervical epithelium from endometrium.

PMID- 16637512
TI  - Routine assessment of hormonal receptor and her-2/neu status underscores the need
      for more therapeutic targets in Kenyan women with breast cancer.
AB  - OBJECTIVE: To report the expression of estrogen receptors, progesterone receptors
      and human epidermal growth factor receptor (Her-2/neu) in 158 Kenyan women with
      breast cancer and correlation with other prognostic indicators in this high-risk
      group. This study stressed the importance of routine assessment of the steroid
      receptors and Her-2/neu as a mode of therapeutic selection of patients for
      antihormonal or targeting monoclonal antibody (Herceptin) therapy, directed at
      the juxtamembrane domain of Her-2/neu protein in the developing countries such as
      Kenya. STUDY DESIGN: The study population consisted of 158 female patients with
      histologically confirmed breast carcinoma seen at the pathology department of The
      Nairobi Hospital. An immunohistochemical (IHC) study of ER, PR and Her-2/neu was
      conducted, followed by fluorescent in situ hybridization (FISH) validation for
      Her-2/neu gene amplification in cases initially scored as positive 2+ with IHC.
      Mastectomy samples registered at the pathology department of The Nairobi Hospital
      were used for this study. The study was approved by the institution's ethical
      review committee and informed consent obtainedfrom the concerned patients.
      RESULTS: In the studied cohort, positivity for both hormonal receptors and Her
      2/neu was noted in 10 (6.33%) cases and negativity in 44 (27.85%) cases.
      Conversely, Her-2/neu negativity was noted in 32 (20.25%) cases with both steroid
      receptors positive and Her-2/neu positivity with both steroid receptors negative
      in 20 (12.66%) cases. Overall, no predictive factor was found in the Her-2/neu
      amplified 31/153 (20.26%) cases completely assessed with IHC and FISH. Grade III
      invasive ductal carcinomas, however, had a high prevalence of Her-2/neu
      overexpression. Association of both menopausal status (p = 0.044) and
      progesterone receptor status (p = 0.004) with high grade tumors were found to be
      statistically significant at 95% CI (p < 0.5). Consistent with other studies, Her
      2/neu overexpression in this cohort was 20.26%. CONCLUSION: Her-2/neu positivity
      may activate ER expression through signaling kinases, and the combined target of
      mitogenic estrogen plus the monoclonal antibody therapy against Her-2/neu
      overexpressing tumors expand chances of survival for patients in developing
      countries such as Kenya. The cost factor for these tests, selection for
      appropriate combined therapies and lack of awareness were noted as limiting
      factors for access to basic health care service and resulted in advanced tumor
      grade at time of patient presentation.

PMID- 16637513
TI  - Atypical prostatic glandular proliferations on needle biopsy: Diagnostic
      implications, use of immunohistochemistry, and clinical significance.
AB  - In recent times, PSA screening and a substantial increase in prostate needle
      biopsies have not only resulted in detection of minute foci of cancer but have
      also very likely resulted in increased detection of atypical glandular
      proliferations. Not uncommonly, there are only a limited number of atypical
      glands in these biopsies, and these require careful evaluation to enable an
      accurate diagnosis. We describe diagnostic implications, use of
      immunohistochemistry, and clinical significance of these lesions. Foci of
      atypical glands, also labeled atypical small acinar proliferation of uncertain
      significance, have features suspicious for but not diagnostic of cancer. Atypical
      foci include a broad group of lesions of differing clinical significance. These
      include benign, small acinar proliferations mimicking prostate cancer and
      atypical glandular proliferations suspicious for carcinoma. Definite diagnosis
      requires accurate histopathologic assessment and judicious use of
      immunohistochemistry. Patients with atypical glands on prostate needle biopsy
      have a high risk for harboring cancer and therefore have an increased risk for
      having cancer detected in subsequent biopsies.

PMID- 16637514
TI  - Cyclin E as molecular marker in the management of breast cancer: a review.
AB  - Over the past decade numerous molecular markers have been identified that may
      play a role in breast carcinogenesis and prognosis. The most commonly used
      markers in clinical practice are the estrogen receptor, progesterone receptor and
      HER-2/neu. Recent studies found cyclin E to be a promising prognostic indicator
      in breast cancer and examined its potential as a target for therapy. Further
      studies demonstrated that cyclin E levels were periodic during the cell cycle,
      with levels of protein peaking in the G1 phase. This peak in cyclin E levels also
      correlated with maximum enzymatic function of the cyclin E-cdk2 complex,
      suggesting a critical role of cyclin E in regulating G1 to S-phase transition.
      Studies examining the relevance of cyclin E alterations in breast cancer have
      shown gene amplifications in some breast cancer cell lines, data that provide
      strong support for the role of cyclin E in breast carcinogenesis. It is believed
      that the most significant cyclin E alteration is post-translational cleavage of
      full-length cyclin E into low molecular weight forms that are hyperactive
      compared to the 50-kDa, full-length protein and correlate with increasing stage
      and grade of breast cancer. The role of cyclin E in the prognosis and therapy of
      breast cancer is reviewed according to recent publications.

PMID- 16637515
TI  - Elastin distribution in the normal uterus, uterine leiomyomas, adenomyosis and
      adenomyomas: a comparison.
AB  - OBJECTIVE: To describe the histologic distribution of elastin in the nonpregnant
      human uterus, uterine leiomyomas, adenomyosis and adenomyomas. STUDY DESIGN:
      Uteri were obtained from women undergoing hysterectomy for benign conditions,
      including 26 cases of uterine leiomyomas, 24 cases of adenomyosis, 18 adenomyomas
      and 6 cases of autopsy specimens. Specific histochemical staining techniques were
      employed in order to demonstrate the distribution of elastin. RESULTS: The
      distribution of elastin components in the uterus was markedly uneven and showed a
      decreasing gradient from outer to inner myometrium. No elastin was present within
      leiomyomas, adenomyomas or adenomyosis. CONCLUSION: The distribution of elastin
      may help explain the normal function of the myometrium in labor. It implies that
      the uneven distribution of elastin components and absence of elastin within
      leiomyomas, adenomyomas and adenomyosis could be of some clinical significance.
      The altered elastin distribution in disease states may help explain such symptoms
      as dysmenorrhea in uterine endometriosis.

PMID- 16637516
TI  - Magnet makes an attractive marketing tool.

PMID- 16637517
TI  - A primer on randomized controlled trials.
AB  - Randomized Clinical Trials are held as the gold standard for quantifying the
      effect of an intervention across two or more groups. In such a trial an
      intervention is randomly allocated to one of two groups. The benefit of such a
      trial lies in its ability to establish nearly comparable groups of subjects in
      all manner except for the effect of the intervention. As such, the effect of a
      given intervention may be attributed solely to the intervention and not to any
      other extraneous factor. In the following editorial, we will discuss several
      issues that are important for understanding how to conduct and interpret
      randomized trials: choosing the study population, choosing the comparison group,
      choosing your outcome, study design, data analysis, and issues of inference. This
      editorial is intended to make the reader an educated consumer of such trial
      designs.

PMID- 16637518
TI  - Whole blood cardioplegia (minicardioplegia) reduces myocardial edema after
      ischemic injury and cardiopulmonary bypass.
AB  - While blood:crystalloid cardioplegia is the clinical standard for patients
      undergoing cardiopulmonary bypass (CPB), it has been postulated that whole blood
      minicardioplegia may benefit the severely injured heart by reducing cardioplegic
      volume, thereby reducing myocardial edema. To test this hypothesis, we compared
      the cardioprotection of a popular 4:1 blood:crystalloid cardioplegia to whole
      blood minicardioplegia (WB) in a porcine model of acute myocardial ischemia.
      Yorkshire pigs (n = 20) were placed on atriofemoral bypass and subjected to 30
      minutes of global normothermic ischemia. Animals were randomized to receive
      either 4:1 cold cardioplegia (n = 10) or WB cold cardioplegia (n = 10) delivered
      antegrade continuously for 90 minutes. Baseline (BL) echocardiographic
      determination of left ventricular mass (LVM) was compared within groups for
      cardiac edema (%) measured by histologic morphometrics. All (100%) animals
      receiving WB were successfully weaned off CPB, whereas only 40% of animals
      receiving 4:1 were successfully weaned off CPB. Cardiac edema percentage (p <
      .004) and LVM (p < .05) were significantly decreased in the WB group compared
      with 4:1. WB cardioplegia increases the number of hearts successfully weaned from
      CPB and decreases cardiac edema in our porcine model of acute myocardial
      ischemia. This finding implies whole blood cardioplegia may be more protective in
      a select group of patients undergoing extended CPB time by decreasing myocardial
      edema.

PMID- 16637519
TI  - Evaluation of biocompatible cardiopulmonary bypass circuit use during pediatric
      open heart surgery.
AB  - The contact of blood with nonbiological surfaces during cardiopulmonary bypass
      (CPB) induces a whole body inflammatory response and increases postoperative
      morbidity directly related to bleeding complications and end organ dysfunction.
      Methods to reduce these effects have included modification of extracorporeal
      circuits through biocompatible coating of disposables and the application of
      various pharmacological agents. Biocompatible coated surfaces are designed to
      mimic physiologic surfaces. This study was designed to ascertain the effects of
      using coated circuits during pediatric CPB. After Institutional Review Board
      approval and parent/guardian consent, patients undergoing CPB, weighing less than
      15 kg, with target CPB temperatures more than 28 degrees C, were enrolled into
      the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2
      methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n = 16).
      Those patients were retrospectively matched to control patients having the same
      congenital repair with respect to patient size, surgeon, anesthesiologist, bypass
      time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n
      = 16). CPB data collected included on-bypass platelet count, hematocrit (HCT),
      and CPB blood product use. Postprotamine data collected in the operating room
      included blood product use, time from initial protamine administration to chest
      closure, platelet count, prothrombin time (PT), activated partial thromboplastin
      time (aPTT), and international normalized ratio (INR). Postoperative intensive
      care unit (ICU) data included blood product use, HCT, chest tube output, platelet
      count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4,
      6, 12, and 24 hours. Other data collected included intubation time, length of
      time to chest tube removal, and length of ICU stay. Statistical significance (p <
      .05) was seen in units of platelets transfused postprotamine, ventilator peak
      inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red
      blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2,
      4, 6, and 12 hours postoperative. Several parameters approached statistical
      significance, including PRBC transfused postprotamine, time from protamine
      administration to chest closure, postoperative day 0 platelets transfused, and
      ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used
      safely during pediatric heart surgery, resulting in a decrease in postoperative
      blood product use, improved postoperative lung function, and a reduction in the
      time spent in the ICU.

PMID- 16637520
TI  - In vivo comparison study of FDA-approved surface-modifying additives and poly-2
      methoxyethylacrylate circuit surfaces coatings during cardiopulmonary bypass.
AB  - The purpose of this double-blind prospective and randomized study was to examine
      the effects of surface-modifying additives (SMAs) and poly-2-methoxyethylacrylate
      (PMEA) circuits on platelet count, platelet function (Sonoclot), postoperative
      chest tube drainage volume, peri- and postoperative blood product use, extubation
      time, and intensive care time. Terumo noncoated, Terumo-coated (PMEA), Cobe
      noncoated, and Cobe coated (SMA) circuits were evaluated to find the most cost
      effective way to improve patient outcomes. We aimed to find if an additional
      charge for a coated CPB circuit would be recovered by reducing other patient
      costs (blood transfusions, intensive care unit time, and bring back postoperative
      bleeding). An initial literature review revealed the comparison of PMEA circuits
      vs. noncoated circuits and SMA circuits vs. noncoated circuits in both adult and
      porcine models. Both SMA- and PMEA-coated circuits decreased platelet
      consumption, platelet factor release, and the overall perioperative inflammatory
      response while on cardiopulmonary bypass (CPB). The question not answered in an
      initial search was simply, "which coated circuit is best for the patient: SMA or
      PMEA?" Research comparing the above coated circuits each other was not found. The
      study was approved by the Institutional Review Board. Thirty patients were
      scheduled for elective coronary artery bypass grafting and/ or valvular repair or
      replacement surgery. These 30 patients were randomized as 10 patients to Terumo X
      Coating (PMEA surface coating) (CT), 10 patients to Cobe Smart-X coating (SMA
      surface coating; CC), 5 patients to Terumo noncoated tubing (NCT), and 5 patients
      to Cobe noncoated tubing (NCC). Informed consent was obtained from each patient
      before surgery. The data showed no statistically significant relationship between
      platelet counts, platelet function (Sonoclot), postoperative chest tube drainage
      volume, peri- and postoperative blood products, intensive care unit time, or
      total hospital length of stay. Analysis revealed statistically significant
      clinical associations of extubation time and protamine dose with treatment group.
      This study provided evidence that SMA- and PMEA-coated circuits do not improve
      platelet consumption or decrease blood product use for patients undergoing CPB.
      There was statistical significance with a reduction in extubation time and total
      protamine requirement needed to return activated clotting time (ACT) to baseline
      post-CPB. Although the use of SMA and/or PMEA circuits during CPB has clinical
      benefit to the CPB patient, an additional charge for the specialty circuit may
      not be realized.

PMID- 16637521
TI  - Heparin-coated adult ECMO vs. ventricular assist devices: a decision analysis
      modeling approach.
AB  - Postcardiotomy failure requiring ventricular assist occurs in about 1% of adult
      patients undergoing cardiac surgical procedures. One method of support is a short
      term ventricular assist device. This incurs the cost of the device, which is
      substantial, and allows for reduced anticoagulation in the first 24 hours.
      Another option is a heparin-coated extracorporeal membrane oxygenation (ECMO)
      circuit. This also allows for reduced anticoagulation and can support the lungs
      if necessary. The use of a heparin-coated ECMO circuit requires 24-hour
      monitoring, but the cost of disposables is considerably less than the cost of
      ventricular assist devices. This decision analysis uses a Markov model to
      evaluate the relative outcomes and costs associated with selection between these
      modalities of support. Data from the past 5 years of patients who received
      postcardiotomy support will be used to develop the Markov model. The hypothesis
      is that supporting the patient on heparin-coated ECMO before instituting
      ventricular assistance will reduce cost and allocate resources in a more cost
      effective manner. The model was used to determine the optimal economic time for
      initiation of ventricular assist devices in postcardiotomy patients. The total
      costs associated with support begin to level out between postoperative days 6 and
      10 using an Abiomed BVS5000 ventricular assist device. The largest decline in
      costs occurs after postoperative day 3. This model suggests that patients should
      be supported on heparin-coated ECMO for 2-3 days to evaluate their potential for
      recovery before instituting more expensive ventricular assist devices.

PMID- 16637522
TI  - Successful use of a competency step exam in a perfusion education program.
AB  - The perfusion education program at The Ohio State University uses a step exam to
      rank students and identify incompetent students in regard to the program learning
      objectives. The step exam determines student progress from the didactic to the
      clinical phase. Each student must pass the competency step exam to gain entry to
      the clinical rotations. The development, use, and results of the step exam are
      reported. The design and knowledge matrix establish the content validity of the
      exam. Single test question discrimination and difficulty statistics identify
      valid exam items. Examples of the exam's predictive ability are presented. The
      step exam is a 200-question exam using multiple choice items. The exam is modeled
      after several health-related national certification exam processes. The exam has
      content validity based on the published, written objectives for the education
      program. Each item on the exam has a history of use and meets criteria for
      difficulty, discrimination, and distraction. The use of a high-stake competency
      exam in clinical science and medical education programs is controversial and
      technically challenging. A step exam to have high-stake consequences must be
      reliable, meet requirements for content validity, and hopefully exhibit
      predictive validity.

PMID- 16637523
TI  - Autologous platelet concentrate and vacuum-assisted closure device use in a
      nonhealing total knee replacement.
AB  - Following a total knee replacement surgery, a 51-year-old insulin-dependent
      patient presented with complications of impaired healing and postoperative trauma
      to the wound site. The inability of this leg wound to heal placed this patient at
      risk of amputation. Vacuum-assisted closure therapy was initiated at
      postoperative day 53; after 100 days of protracted wound history a series of
      treatments with topical platelet concentrates were added to the vacuum assisted
      closure therapy and conventional wound care therapy. The previous nonhealing
      wound presented with good granulation and margination that enabled a skin graft
      with good take on postoperative day 150.

PMID- 16637524
TI  - Genetics and outcome after cardiac surgery.

PMID- 16637525
TI  - Development of a novel perfusion technique to allow targeted delivery of gene
      therapy--the V-Focus system.

PMID- 16637526
TI  - Thrombin inhibitors and cardiopulmonary bypass.

PMID- 16637527
TI  - Urban myths and the ACT: what is not true and what really matters when it comes
      to monitoring anticoagulation.

PMID- 16637529
TI  - Ultrafiltration techniques and CPB: what we know and what we think we know.
AB  - Unfortunately there have been very few prospective randomized studies comparing
      the clinical outcomes of patients treated with large volume ultrafiltration.
      Given the shortage of impressive clinical outcome data and the varying results of
      mediator removal studies, the application of ultrafiltration as a therapeutic
      technique is still a controversial topic. A few researchers have suggested that
      different membrane materials may have significantly different mediator removal
      potential. One important future direction for research in this area should
      include a comprehensive comparison of different membrane materials with regard to
      their clinical performance.

PMID- 16637528
TI  - From trash to leucocytes: what are we filtering and why?

PMID- 16637530
TI  - Glucose and outcome after cardiac surgery: what are the issues?

PMID- 16637531
TI  - Glucose monitoring on CPB.

PMID- 16637532
TI  - Review on the usage of mannitol during cardiopulmonary bypass.

PMID- 16637533
TI  - What blood pressure is appropriate for cardiopulmonary bypass and how to get it.

PMID- 16637534
TI  - Conducting clinical trials.

PMID- 16637535
TI  - Pericardial suction blood--what are we doing about it?

PMID- 16637536
TI  - The OXICAB trial: cerebral oximetry in adult cardiac surgical patients.

PMID- 16637537
TI  - Perioperative temperature and cardiac surgery.

PMID- 16637539
TI  - A pilgrim in Banda Aceh. A Bon Secours sister witnesses rebuilding and healing in
      tsunami-ravaged Indonesia.

PMID- 16637538
TI  - "Covering the uninsured" is a flawed moral frame.

PMID- 16637540
TI  - Ethics committees in Catholic hospitals. A new study assesses their role, impact,
      and future in CHA-member hospitals.
AB  - The role, effectiveness, and even existence of hospital ethics committees (HECs)
      are not universally agreed upon. Over the past 20 years, the study of HECs has
      focused mainly on their structure, scope, and function, making the results more
      descriptive than anything. In an effort to present study results that could help
      HECs better serve the needs of their organizations, the authors of this article
      recently set out to survey HEC chairs at CHA-member hospitals, asking questions
      about four key areas: 1) primary functions of an HEC, 2) selection criteria of
      HEC members, 3) strategies for success, and 4) the importance of HEC member
      training. The results of this survey provide some important food for thought.

PMID- 16637541
TI  - A "next generation" ethics committee. St. Joseph Health system has integrated
      performance-improvement features into its ethics work.
AB  - Understanding the limitations that accompany the traditional model of ethics
      committees, St. Joseph Health System (SJHS), Orange, CA, has been working to
      integrate ethics expertise and quality-improvement methodology into its "Next
      Generation Model" (NG Model) for such committees. However, moving from a
      traditional structure to the NG Model (introduced to SJHS facilities in 1999)
      brought some challenges, not the least of which was a deep-rooted culture of
      resistance to change. Following a 2004 audit of how the NG model was working,
      some common challenges were identified. To deal with those challenges, SJHS
      developed some tools and techniques that have helped ease the ongoing transition.
      These tools have helped the system's ethics committees address such issues as
      collaboration for the sake of organizational integration, setting goals, and
      measuring performance of various ethics roles.

PMID- 16637542
TI  - Integrating clinical and organizational ethics. A systems perspective can provide
      an antidote to the "silo" problem in clinical ethics consultations.
AB  - Traditionally, ethics consultations are conducted one case at a time. This
      typical approach addresses immediate needs pertinent to the case, but seldom
      looks toward preventing recurrences. The underlying problem is that clinical
      ethics and organizational ethics are still often regarded as separate areas with
      separate concerns. When it comes to ethics in health care, nothing helps clarify
      ideas like a case study. The autopsy case mentioned in this article demonstrates
      that clinical cases coming before an ethics committee are impeded in and
      influenced by a larger organizational context. The authors say that a "systems
      oriented" perspective toward ethics consultation would help committee members
      view cases through the widest possible lens. This would enable committees to look
      at the larger system and thereby propose strategies for anticipated repeat
      problems.

PMID- 16637543
TI  - Ethics consultation in Portland. Providence Health's Oregon Region has created an
      ethics consult service.
AB  - In response to the need for a more structured approach toward the enhancement of
      and preparation for case consultation, the Portland Service Area (PSA) of the
      Providence Health System Oregon Region implemented a "special team" system. These
      teams--an extension of the ethics committees already in place--underwent training
      in areas such as an overview of ethics, patient decision making, professionalism,
      organizational ethics, and palliative and end-of-life care. Moving ethics
      consultation away from the purview of ethics committees generally, and into the
      realm of these trained special teams, has improved PSA's ability to respond to
      ethics needs in the region.

PMID- 16637544
TI  - St. Louis system has Corporate Ethics Committee. Sisters of Mercy Health System
      has developed an approach for assisting in the integration of ethics and
      operations.
AB  - Despite the relatively recent advent of organizational ethics committees--created
      to address operational concerns that are not always appropriate for a clinical
      ethics committee to take on--there remain impediments (such as time constraints,
      limited ethical expertise, lack of senior leaders at the table, and waning
      interest of members) to the impact such a group might have. Committed to
      addressing operational concerns in a meaningful and "value-added" way, and
      mindful of the challenges that can limit the effectiveness of organizational
      ethics committees, the St. Louis-based Sisters of Mercy Health System developed
      an approach that has proven successful. Without changing the committee's goals
      education, policy, and consultation-Mercy's renewed Corporate Ethics Committee
      was restructured to include ethical experts, people knowledgeable about
      particular issues, and people with authority.

PMID- 16637545
TI  - Canon law and mortgages. Does Canon Law speak about mortgaging property?

PMID- 16637546
TI  - Cardiology and genomics: a medical view.

PMID- 16637547
TI  - Cardiology and genomics: an ethical view.

PMID- 16637549
TI  - Gastrointestinal considerations.

PMID- 16637548
TI  - Vocation lost? Hospitals must bring physicians back into the mission of medicine.

PMID- 16637550
TI  - Gastrointestinal complaints.

PMID- 16637551
TI  - A 5-week-old boy with rhinorrhea, fever.

PMID- 16637552
TI  - A 5-month-old boy with white spots on his skin.

PMID- 16637553
TI  - Chronic abdominal pain of functional origin in children.
AB  - Many future investigations into FGIDs are needed. These should focus on refining
      and validating the Rome diagnostic criteria, investigating possible biologic
      markers of these disorders, elucidating the role of the visceral afferent
      dysfunction or reflex motor responses that lead to symptoms, searching for new
      pathogenic factors (eg, corticotrophin-releasing factor), and evaluating
      therapies in prospective controlled trials. To tackle this challenging group of
      disorders successfully, there must be a broad collaboration among basic
      scientists, clinical investigators, physicians, psychologists, and practitioners
      of alternative and complementary medicine to develop and evaluate improved
      therapies. In the meantime, it is our duty as practitioners to keep updated and
      receptive to the needs of patients and families to reduce patient suffering,
      improve functioning, and control the costs to society.

PMID- 16637554
TI  - Gastroesophageal reflux in infancy and childhood.
AB  - GER is a common reason for pediatric office visits and referrals to a pediatric
      gastroenterologist. This condition frequently is benign, and it is self-limited
      in most infants. Although a thorough history and complete physical examination
      usually are adequate to diagnose GER, a high index of suspicion must be
      maintained for other diagnoses associated with recurrent emesis, including
      metabolic disorders, as well as for other gastrointestinal conditions, such as
      pyloric stenosis and abnormalities of intestinal rotation. Behavioral or
      lifestyle modification usually can be implemented empirically to diagnose and
      manage a suspected case of uncomplicated GER. When this fails, medical therapy
      can be initiated, employing either a step-up or step-down approach with a PPI or
      H2RA. With the proven efficacy of PPIs and their availability to children,
      medical treatment has become the mainstay of therapy in severely affected
      patients; nevertheless, anti-reflux surgery is still widely performed in children
      with GER. Pediatricians and other primary care providers often manage infants and
      children who have gastrointestinal complaints, prior to referral to a pediatric
      gastroenterologist. Hence, they have the responsibility to educate children and
      families about GER, its natural history, complications, and therapeutic options.
      A careful history and physical examination, informed use of diagnostic studies,
      and a consistent approach to medical treatment are important principles that are
      required to guarantee the success of GER management in infants and children.

PMID- 16637555
TI  - Inflammatory bowel diseases.
AB  - The inflammatory bowel diseases remain at the forefront of clinical
      investigation. Immunologic and genetic advances are fueling an explosion of novel
      diagnostic and therapeutic modalities. With further breakthroughs, there is hope
      that in the near future, these illnesses will no longer be considered either
      idiopathic or chronic.

PMID- 16637556
TI  - Celiac disease in the pediatric population.

PMID- 16637557
TI  - Neonatal liver disease.
AB  - Establishing a rapid and accurate diagnosis of the cause of neonatal liver
      disease is an urgent matter. The initial detection of this condition relies on
      the sensitivity of the primary care provider or pediatrician to the signs and
      symptoms of jaundice and abnormal stool and urine color. It is critical to
      evaluate jaundice in any infant older than 2 weeks with measurement of
      fractionated bilirubin, and further assessment is necessary if the direct value
      is above 1.0 mg/dL in the setting of a total bilirubin of less than 5.0 mg/dL or
      a direct bilirubin of more than 20% of total if the total is more than 5.0 mg/dL.
      A diagnostic algorithm for the evaluation of infants who meet these criteria can
      guide physicians in selecting appropriate and timely diagnostic testing and
      referral to pediatric gastroenterology for these patients, whose outcome will
      rely on rapid diagnosis.

PMID- 16637558
TI  - Nonalcoholic fatty liver disease.
AB  - NAFLD likely is the most common liver disease in children and is responsible for
      significant progression to cirrhosis, portal hypertension, and the need for liver
      transplantation in adults and even in some adolescents. Early diagnosis and
      lifestyle interventions appear to be our best hope for controlling progression of
      disease. The pediatrician is responsible for screening all obese children with
      measurement of aminotransferases. Those with elevated enzymes (particularly ALT)
      for longer than 3 months, in the absence of markers of hepatitis B or C,
      autoimmune chronic active hepatitis, Wilson's disease, hemochromatosis, or alpha
      1-antitrypsin deficiency, should follow up with an abdominal ultrasound. In
      patients with a BMI in the morbidly obese range, an ultrasound to search for a
      diffusely echogenic liver should be performed even if the liver enzymes are
      normal. Findings suggestive of NAFLD should prompt the institution of appropriate
      dietary and exercise regimens. If these are unsuccessful after a 3-month trial,
      the patient should be referred to a pediatric gastroenterologist and hepatologist
      for further work-up and treatment, preferably in the context of a controlled
      therapeutic trial. Only by aggressively engaging this current epidemic will we be
      able to decrease the mounting human cost of NAFLD.

PMID- 16637559
TI  - The history you know.

PMID- 16637560
TI  - Community urbanization and hospitalization of adults for asthma.
AB  - Asthma research has traditionally focused on children and the elderly, the two
      populations considered most susceptible to complications. The prevalence of
      asthma in the adult population (19-64 years of age) is, however, gaining
      recognition as a formidable clinical and public health problem. Few studies have
      compared the incidence of adult asthma hospitalizations in urban and nonurban
      areas. The study reported here, using population size, population density, and
      traffic-related factors to define urban versus nonurban environments, selected
      six Pennsylvania counties to test the hypothesis that the degree of urbanization
      influences the asthma hospitalization rate for adults. The study group comprised
      adults 19-64 years of age who were hospitalized for asthma (as the primary
      diagnosis) from 1999 to 2001. To define urbanization in relation to traffic, the
      study used daily vehicular traffic count and miles of roads/highways for each of
      the six counties. The authors found a decrease in the adult asthma
      hospitalization rate as urbanization decreased in some of the counties. For other
      counties, however, the rate increased as urbanization decreased. The counties in
      which the latter was observed had depressed measures of socioeconomic status.
      These findings suggest that depressed socioeconomic conditions may supersede
      exposure to traffic-related pollution as a factor associated with asthma
      hospitalizations.

PMID- 16637561
TI  - Simple and rapid method for detection of bacterial spores in powder useful for
      first responders.
AB  - The need for a rapid method by which first responders can screen for the presence
      of spores in powder samples has been increased since the anthrax attack of 2001.
      The majority of powders that were sampled in the context of that attack were
      hoaxes and did not contain Bacillus anthracis. The large number of samples
      overwhelmed the analysis capacity of public health laboratories. A rapid
      screening method for determining the presence of viable spores would eliminate
      much laboratory work and expedite procedures for identification if spores were
      detected. In the study reported here, Bacillus thuringiensis was used as a
      surrogate for B. anthracis to investigate if heat shock followed by luminescence
      analysis would allow rapid quantification of viable spores. The aim of the study
      was to investigate the best and fastest heat shock conditions that would trigger
      the breakdown of endospore dormancy of Bacillus species and give a higher
      luminescence signal. Heat shock and luminescence do not identify the type of
      spores in a powder sample, but they can detect the presence of viable spores in
      near real time. Different types of germinant were tested at different conditions
      (germination duration, temperature, concentration). The rapid method was compared
      with the traditional plate count method. The results showed that the rapid method
      can be used as a rapid (< 15 min), sensitive (< 100 spores), and inexpensive
      detection technique. The rapid method can be applied on site when suspicious
      powder is found and enables decision making for further identification.

PMID- 16637562
TI  - Evaluation of a model training program for respiratory-protection preparedness at
      local health departments.
AB  - Respiratory-protection programs have had limited application in local health
      departments and have mostly focused on protecting employees against exposure to
      tuberculosis (TB). The need to provide the public health workforce with effective
      respiratory protection has, however, been underscored by recent concerns about
      emerging infectious diseases, bioterrorism attacks, drug-resistant microbes, and
      environmental exposures to microbial allergens (as in recent hurricane flood
      waters). Furthermore, OSHA has revoked the TB standard traditionally followed by
      local health departments, replacing it with a more stringent regulation. The
      additional OSHA requirements may place increased burdens on health departments
      with limited resources and time. For these reasons, the North Carolina Office of
      Public Health Preparedness and Response and industrial hygienists of the Public
      Health Regional Surveillance Teams have developed a training program to
      facilitate implementation of respiratory protection programs at local health
      departments. To date, more than 1,400 North Carolina health department employees
      have been properly fit-tested for respirator use and have received training in
      all aspects of respiratory protection. This article gives an overview of the
      development and evaluation of the program. The training approach presented here
      can serve as a model that other health departments and organizations can use in
      implementing similar respiratory-protection programs.

PMID- 16637563
TI  - CDC and HUD to release an updated housing inspection manual--the Healthy Housing
      Reference Manual.

PMID- 16637564
TI  - The legal implications of "toxic" mold exposure.

PMID- 16637565
TI  - Legal authorities for isolation and quarantine--information from CDC.

PMID- 16637566
TI  - NEHA communicates its views to Congress.

PMID- 16637567
TI  - [Stanniocalcin-1 (STC-1) as a molecular marker for human cancer].
AB  - Stanniocalcin (STC) is a glycoprotein hormone that regulates calcium levels in
      fish. The related human protein stanniocalcin-1 (STC-1) is expressed in multiple
      organs including the ovary, prostate, kidney, and thyroid. Human STC-1 expression
      is enhanced by neural cell differentiation, bone formation, and cell
      proliferation. Recently, quantitative RT-PCR analysis showed high levels of STC-1
      mRNA in the blood of patients with cancer as compared with those in the blood of
      volunteers without cancer. The STC-1 mRNA expression in blood is closely related
      to tumor size in breast cancer, micrometastases of hepatocellular carcinoma, and
      minimal residual disease in leukemia. This brief review describes the diagnostic
      significance of STC-1 as a molecular marker for human cancer.

PMID- 16637568
TI  - Cerebral mature teratoma with malignant transformation in a 52-year-old man: a
      case report.
AB  - A case of adult teratoma with malignant transformation in a 52-year-old male is
      reported. We describe characteristic CT, histopathologic features and
      histogenesis of the tumor. Gradual onset of cerebral signs and symptoms was
      considered to be due to the tumor originating from the silent area of the frontal
      lobe of the brain and possessing a slowly progressive growth character.

PMID- 16637569
TI  - [Report on a training course for clinical research coordinators].
AB  - Recently, nurses and pharmacists have become to play important roles in clinical
      trials as clinical research coordinators (CRC). However, clinical laboratory
      personnel have a very few chances to contribute to such tasks. CRCs have
      responsibility to protect the human rights, to assure the safety of volunteers
      during studies, and to keep quality of data. One of the authors had a chance to
      participate in a training course for CRC that was held in Tokyo, 2004. In this
      paper, we report about the training course and roles of CRC. We also discuss how
      laboratory personnel should contribute to clinical trials.

PMID- 16637570
TI  - [Effort in standardization of control survey using pooled fresh serum in Okayama
      Prefecture].
AB  - Control survey of the clinical laboratories in Okayama Prefecture has been
      continued once a year for 18 years using commercially available control serum.
      The purpose of our control survey is to minimize the difference of laboratory
      test data among laboratories. It is clear, however, that one time a year survey
      leads to miss-evaluation of the difference in laboratory test result. Furthermore
      the data difference caused by difference of assay methods, for example dry
      chemistry and wet chemistry, is not properly evaluated by control survey using
      control serum, since test result is affected by matrix effect. Therefore we have
      developed a monthly control survey program, Okayama cross-check program, using
      pooled fresh serum among laboratories of middle-large scale hospitals and
      commercial laboratories in Okayama prefecture. In this paper we describe the
      details of Okayama cross-check program and the usefulness of the program to
      reduce the difference among laboratory facilities. This result was attained by
      cooperation of the Okayama prefectural medical association, Okayama association
      of medical technologists, and commercial laboratories in Okayama.

PMID- 16637571
TI  - [Present state of outpatient consultation in Gunma University Hospital].
AB  - We started outpatient consultation by clinical laboratory physicians in Gunma
      University Hospital in June, 2002. Three days a week, five clinical laboratory
      physicians examine outpatients or answer questions concerning laboratory tests in
      an outpatient consulting room. The number of outpatients referred has gradually
      increased since we started this consultation. Among the wide rage of cases
      examined, there have been many preoperative patients with eye disorders from the
      Department of Ophthalmology. There are some advantages of our outpatient
      consultation. For example, we are able to give patients a detailed and unrushed
      explanation of their laboratory data, and close cooperation with clinical
      laboratory technicians enables physicians to perform quick and smooth echo-guided
      fine needle aspiration cytology of thyroid nodules. We hope that our consulting
      work by clinical laboratory physicians will become widely known to patients and
      doctors.

PMID- 16637572
TI  - [Clinical features of a new category, myelodysplastic/myeloproliferative
      diseases, defined by WHO classification].
AB  - The WHO classification published in 2001 defined a new category of hematological
      disease, myelodysplastic/myeloproliferative diseases (MDS/MPD), that have both
      myelodysplasia and myeloproliferation at the time of initial presentation. This
      category consists of four subclasses, chronic myelomonocytic leukemia (CMML),
      atypical CML(aCML), juvenile chronic myelogenous leukemia and MDS/MPD
      unclassifiable (MDS/MPD-u). In order to clarify the clinical features of these
      diseases, we analyzed clinical data of tentatively diagnosed MDS/MPD cases in the
      past ten years accumulated from affiliated hospitals. By reviewing the data of
      each case according to the criteria, we diagnosed 31 cases of MDS/MPD, including
      22 cases of CMML, 5 cases of aCML and 4 cases of MDS/MPD-u. Male predominance and
      high age were common among these three subclasses. The prognosis of CMML was poor
      compared to other subclasses because of the high incidence of blast crisis. It is
      noteworthy that blast crisis in CMML exclusively occurred within one year after
      diagnosis. Young age, a high percentage of blasts in the peripheral blood,
      splenomegaly, lymphadenopathy and clonal cytogenetic abnormality were associated
      with blast crisis. It is suggested that there are two subgroups in CMML which
      differ in disease progression. Thus, these indicators may be useful in deciding
      the therapeutic strategy including hematopoietic cell transplantation for the
      high risk subgroup. There were four MDS/MPD cases with a history of preceding
      hematological diseases, such as aplastic anemia, MDS or malignant lymphoma. Among
      these, three cases with a long-term history of treatment with metenolone acetate
      developed CMML. It is suggested that the long-term effect of androgen plays a
      role in the pathophysiology of CMML.

PMID- 16637573
TI  - [Advancement of platelet activation measurement: focusing on platelet-derived
      microparticle measurement].
AB  - The assessment of the extent of platelet activation in various thrombotic
      disorders is important to detect thrombotic tendencies and monitor antiplatelet
      therapy. Various methods (platelet factor 4: PF4, beta-thromboglobulin: beta-TG,
      CD62P, PAC-1, etc.) are used as markers of platelet activation. Platelet-derived
      microparticles (PDMP) are submicroscopic vesicles released by platelets during
      activation, and are used as a marker of platelet activation. PDMP are usually
      determined by flow cytometry. An enzyme-linked immunosorbent assay (ELISA) method
      in which PDMP are detected with the antibody of CD42a and CD42b, was recently
      reported. The PDMP sample for ELISA can be preserved, and standardization is also
      easy. It is expected to become an evaluation method of platelet function in vivo.

PMID- 16637574
TI  - [Phosphatidylserine-dependent anti-prothrombin antibody as a new marker for the
      diagnosis of antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder in which vascular
      thrombosis and recurrent pregnancy loss occur in patients with antiphospholipid
      antibodies(aPL). Measurements of the beta2-glycoprotein I-dependent
      anticardiolipin antibody(aCL) and lupus anticoagulant(LAC) are the only
      laboratory tests available for the diagnosis of APS. Recently, phosphatidylserine
      dependent antiprothrombin antibody(aPS/PT) has been detected. aPS/PT was measured
      by ELISA using the phosphatidylserine-prothrombin complex as an antigen
      immobilized on ELISA plates in the presence of CaCl2. In our study of 219
      patients with APS and autoimmune diseases, the prevalence of aPS/PT-IgG in those
      with APS was 42.2%, which was significantly higher than that(4.6%) in patients
      with autoimmune diseases. Furthermore, aPS/PT was closely associated with APS
      manifestations with an odds ratio (OR) of 2.92 (95% confidence interval (95% CI):
      1.33 to approximately 6.40), whereas the OR for aCL was 2.06 (95% CI: 0.91 to
      approximately 4.66). In addition, aPS/PT-IgG was strongly correlated with the
      presence of LAC as detected with a diluted Russell viper venom time test (dRVVT)
      (OR: 38.2, 95% CI: 13.4 to approximately 109.1). The monoclonal antibody (23-1D)
      of aPS/PT also prolonged the clotting time in LAC tests (aPTT, dRVVT, and kaolin
      clotting time) in a concentration-dependent manner. In conclusion, aPS/PT is more
      closely associated with manifestations of APS and LAC, and positive results from
      an aPS/PT test can mark thrombotic events in APS patients. The determination of
      aPS/PT in clinical practice, in conjunction with that of other aPL, may improve
      the likelihood of recognizing APS.

PMID- 16637575
TI  - [Band 3 protein as a metabolic sensor--CO2 regulates the amount of oxygen
      delivered to tissues from red blood cells].
AB  - Oxygen is essential for most forms of life, but too much oxygen is harmful and
      can induce tissue damage. Living creatures therefore have a tightly regulated
      system to deliver the necessary amount of oxygen to specific tissues at the right
      time. CO2 is not simply waste matter from tissues, but regulates the amount of
      oxygen delivered to tissues from red blood cells, utilizing the synergistic
      effects of hemoglobin, carbonic anhydrase and the anion exchange activity of band
      3 protein. Red blood cells play an important role in this system and provide an
      ideal vehicle for delivering oxygen to tissues, depending on their metabolic
      activity.

PMID- 16637576
TI  - [Promotion of the systematization of consistent education for medical
      technologists].
AB  - Although only about 35 years have passed since the birth of medical technology,
      marked advances have been made in the clinical laboratory science field. However,
      the educational system for technologists attached importance only to the learning
      of techniques for a long period because special training schools primarily
      provided medical technologist education. With the passing of time, the need for
      advanced knowledge has increased, and a plan to change the education system for
      medical technologists to 4-year colleges was evaluated. In 1989, the Course of
      Laboratory Sciences as a 4-year system for medical technologist education was
      established in the Department of Medicine, Tokyo Medical & Dental University. The
      Doctoral Course of Graduate School (first term) was established in 1993 and the
      Doctoral Course of Graduate School(second term) in 1995. In 2001, these courses
      formed a graduate university as the Division of Biomedical Laboratory Sciences,
      the Graduate School of Allied Health Sciences. Thus, a consistent educational
      system for medical technologists was established. By March 2005, about 500
      students had graduated from this division. Based on this experience, we produced
      a 4-stage developmental program and provide an advanced educational system for
      the promotion of the systematization of consistent medical technologist
      education.

PMID- 16637577
TI  - [Examinations and exercises in medical technology utilizing a personal computer
      and the web].
AB  - The practice of e-learning in our department utilizing freeware without
      additional cost has been introduced: 1) Examinations and exercises are performed
      on the Web. Using the form-filling format of HTML, multiple-choice questions are
      asked. When the examinee submits the answers, the server will process the data
      using active server pages and send the result to the examinee with the score and
      explanations. So far, the students have given the Web examination (exercise)
      system a good evaluation. Concerning the effect of the explanations given in the
      Web exercises on the written test, some improvements were observed in the
      enumeration-type questions. On the other hand, no such improvements were clearly
      observed in the explanation-type questions, which require essential understanding
      of the principle. This suggests that effective utilization of the materials
      strongly depends on the students' eagerness to study. 2) To understand the
      chemical structures of body constituents, an exercise to draw structural formulae
      on the personal computer (PC) is performed. The students had difficulty in the
      fine control of arranging the whole shape of the formula, in addition to setting
      the format of characters such as super- and subscripts. In respect of
      understanding, they had significant difficulty in finding the structures and in
      distinguishing stereoisomers; however, the students had fun with the structure
      drawing software and found it convenient to draw structures. These findings
      suggest that PC exercises will be attractive to students of the "PC generation",
      and thus helpful for the understanding of and training in data analysis in
      medical technology.

PMID- 16637578
TI  - [Unique system for education of medical technology and cytotechnology students at
      Kurashiki University of Science and the Arts].
AB  - For students orienting medical technologist (MT) and cytotechnologist (CT), a
      peculiar system of education is operated in Department of Life Science, Kurashiki
      University of Science and the Arts. Forty candidates for MT are selected from 90
      students at end of the university first year. They study from lectures and
      practices specialized in medicine and face another selection at end of the third
      year. Selected candidates (ten and some in number) will challenge examination for
      CT license as well as that for MT license in the forth year in "double-license
      course". Prior to these selections, education for CT is started at the first year
      in order to clarify suitability of each student as a CT from earlier stage. In
      parallel, education for basic medical research is opened to all students at the
      first year for developing another suitability in them. Topics in cytopathology,
      neuroscience, cellular culture and regenerative medicine are presented to
      stimulate their interest in graduate school. Kake Educational Institution
      Cytopathological Center is located in the university campus and provides
      excellent facility for basic medical research. The university develops talent of
      students both for MT and CT through license acquisition and basic researcher for
      modern medicine in collaboration with this research center. The premier group of
      students under application of this system is active at the third year at present.
      They understand their own suitability and spend their time in the best manner
      toward their goal. We are confident that this system activates talent of students
      without overload.

PMID- 16637579
TI  - [Integrative medicine in health science education].
AB  - Integrative Medicine (IM) is a concern of many people. We consider IM to be very
      important in Health Science, especially Clinical Laboratory Science. We will
      start a new program named "Introduction to Integrative Health Science", which
      covers the relationship of Health Science and IM, in addition to "Introduction to
      Healthy Food and Supplement". These programs will bring a new angle to the
      education of Clinical Laboratory Science as Health Science. We have held various
      community health education sessions about IM, which have helped to explain
      Clinical Laboratory Science as well as the scientific evaluation of IM. We hope
      that Clinical Laboratory Science Education will develop further in the future.

PMID- 16637580
TI  - [Extensive educational program for high performance medical technologists].
AB  - The education system for medical technologists has recently been revolutionized,
      their educational periods vary from 2 to 9 years, and some already have doctoral
      degrees. In such a new situation, our faculty thinks that the most important
      point for new medical technologists is the ability to have a broad view of the
      clinical fields, especially the view of patients. Special training in bed-side
      education and a stint in several divisions, such as the surgical operation room,
      rehabilitation. radiological examination room, pharmacy, central storage room of
      medical records, and medical informatics, and so on, of the hospital is a
      powerful tool to obtain a broad view of the various clinical fields and can be
      essential for developing high performance medical technologists. As nine years
      have passed since starting this education, we evaluated this practice through
      systematic personal communication. As a result, it was found to be extremely
      effective for many reasons such as having a continuous image of the patient when
      they examine the blood sample in the hospital laboratory, showing advanced
      laboratory performance, and having no mental barrier to visiting the wards and so
      on. The abilities of our alumni are praised highly by many large scale hospitals
      around the country and 50% of them are working in the clinical laboratory
      division of these hospitals. About 40% are working in the division of research
      and development in various companies. We express sincere thanks to the director
      and all cooperative individuals for this course in the Osaka University Hospital.

PMID- 16637581
TI  - [Education for medical teamwork in Shinshu University].
AB  - Both students of health sciences (medical technology, nursing science, physical
      therapy, and occupational therapy) and medical students learn medical teamwork in
      the primary stage by joint practice in Shinshu University. The aim of this class
      is for students that will become medical staff to increase their necessary
      communication skills for medical teamwork in addition to understanding the mutual
      medical professional fields in a medical institution. The 242 students of the
      medical department (147 students of health sciences and 95 students of medicine)
      take 15 classes during their first term as freshers. One teacher takes charge of
      a group consisting of 14 students for tutorials by mutually cooperation between
      teachers of medicine and health sciences. Positive relationships are expected to
      develop in the group, raising sociality and ethics so that both students of
      health science and medicine experience interdisciplinary discussion in small
      groups as an ideal method for continuing health care in times of poor knowledge
      of medicine and health care.

PMID- 16637582
TI  - [The first graduates].
AB  - The Hirosaki University School of Health Sciences, started in April, 2001
      graduated its first student in March, 2005 and we introduced a health studies
      specialty master's course at the same time. We report medical technologist
      training in a principal school and the situation for graduate school master's
      courses. The course of study includes physics, chemistry, biology and statistics
      with a compulsory subject by basic seminar that is an introduction subject, a
      basic education subject, serving as a supplementary lesson and considering the
      professional training to be connected. We mainly receive practical training by
      attending the university hospital clinical central laboratory, pathology, and
      blood transfusion area for three years and can continue for one year to carry out
      graduation study. As for the course situation, a person of entrance into a school
      of higher grade to a graduate school compared 11 students out of 41, company
      relation 4 with the school of allied medical sciences other than finding
      employment in a hospital and clinical laboratory and became various. 19 students
      out of 30 are members of society, and we consider this, and the new student
      situation to Hirosaki University graduate school master's course does a class on
      after half past 5 and Saturday.

PMID- 16637583
TI  - [Educational system for medical sciences at the University of Tsukuba--with
      special reference to medical technology].
AB  - Three-year colleges for nursing, medical technology, and so on, have all been
      reorganized into four-year educational institutions in national universities.
      Since the reform, universities are not responsible for educating medical
      scientists except nurses. The new College of Nursing and Medical Technology in
      the University of Tsukuba has been developed along these lines. Here introduce
      some of its attempts and provide an opportunity to a better system. The
      Department has the following three characteristics: 1. Medical scientists are
      educated in the new Department, and the Department is closely cooperating with
      the School of Medicine. 2. There are courses for medical researchers concerning
      Molecular Pathology, Pathological Engineering and Environmental Pathology. 3. The
      qualification to apply to a national test for medical technologists is given to
      the students. Unfortunately, the system is not fully understood by the faculty or
      the students and does not work well because the Medical Technology Department and
      the Nursing Department are grouped together as a single institution. Moreover,
      this flaw in the system prevents the Medical Technology Department from actively
      promoting highly advanced medical sciences, such as organ transplantation,
      artificial organs, gene therapy, reproductive medicines, and so forth (Fig. 1).
      Few specialists exist who can bridge achievements in basic or advanced sciences
      and clinical application. Serious social problems about food safety, care
      systems, post-genome medicine, the youth, and so on, have to be dealt with, too.
      We are thus planning to separate the Department as the College of Medical Science
      (Fig. 2) and link it to the educational system in the master's and doctoral
      programs (Fig. 3). This model will successfully educate a new type of medical
      specialists.

PMID- 16637584
TI  - [Reflections on my "Clinical study on akinetic epilepsy"].

PMID- 16637585
TI  - [Psychopathological study of lie motif in schizophrenia].
AB  - The theme of a statement is called "lie motif" by the authors when schizophrenic
      patients say "I have lied to anybody". We tried to analyse of the
      psychopathological characteristics and anthropological meanings of the lie motifs
      in schizophrenia, which has not been thematically examined until now, based on 4
      cases, and contrasting with the lie motif (Lugenmotiv) in depression taken up by
      A. Kraus (1989). We classified the lie motifs in schizophrenia into the following
      two types: a) the past directive lie motif: the patients speak about their real
      lie regarding it as a 'petty fault' in their distant past with self-guilty
      feeling, b) the present directive lie motif: the patients say repeatedly 'I have
      lied' (about their present speech and behavior), retreating from their previous
      commitments. The observed false confessions of innocent fault by the patients
      seem to belong to the present directed lie motif. In comparison with the lie
      motif in depression, it is characteristic for the lie motif in schizophrenia that
      the patients feel themselves to already have been caught out by others before
      they confess the lie. The lie motif in schizophrenia seems to come into being
      through the attribution process of taking the others' blame on ones' own
      shoulders, which has been pointed out to be common in the guilt experience in
      schizophrenia. The others' blame on this occasion is due to "the others' gaze" in
      the experience of the initial self-centralization (i.e. non delusional self
      referential experience) in the early stage of schizophrenia (S. Kato 1999). The
      others' gaze is supposed to bring about the feeling of amorphous self-revelation
      which could also be regarded as the guilt feeling without content, to the
      patients. When the guilt feeling is bound with a past concrete fault, the
      patients tell the past directive lie motif. On the other hand, when the patients
      cannot find a past fixed content, and feel their present actions as uncertain and
      experience them as lies, the present directive lie motif is told. Lie motifs are
      considered to have the effect of restoring the patient's own subjectivity by the
      following ways: (a) by actualizing the structural constituents elementary for the
      establishment of subjectivity, (b) by conducting a kind of speech act for
      declaring themselves as an active lying subject to co-presenting others for the
      resettlement in our inter-subjective world.

PMID- 16637586
TI  - [Epilepsy and psychic seizures].
AB  - Various psychic symptoms as ictal manifestation have been found in epileptic
      patients. They are classified as psychic seizures within simple partial seizures,
      and subclassified into affective, cognitive, dysmnesic seizures and so on,
      although the subclassification is not yet satisfactory and almost nothing is
      known about their relationships with normal brain functions. In this
      presentation, the speaker picked ictal fear, deja vu and out-of-body experience
      (OBE) from them and suggested that studies on these symptoms could uniquely
      contribute to the progress of cognitive neuroscience, presenting some results
      from the research and case study that he had been engaged in. Psychic seizures
      are prone to be missed or misdiagnosed unless psychiatrists with sufficient
      knowledge and experience on epilepsy care would not treat them, because they are
      subjective symptoms that are diverse and subtle, while they have some
      characteristics as ictal symptoms.

PMID- 16637587
TI  - [Epilepsy and pseudoseizures derived from their dissociation].
AB  - Many epileptic patients have pseudoseizures (psychogenic nonepileptic seizures
      mimicking epileptic seizures) derived from their dissociation (conversion) or
      other psychiatric symptoms. The pseudoseizure cast many problems on medical
      support for their management. In this article I reported the result of
      investigation of pseudoseizures in an epilepsy unit in department of psychiatry,
      National Center Hospital for Mental, Nervous, and Muscular Disorders, National
      Center of Neurology and Psychiatry. And I reffered to treatment and prognosis of
      pseudoseizures. The key points for psychiatrists in treating epileptic patients
      having pseudoseizures were; 1) not to hesitate to consult with specialists about
      diagnosis, 2) to distinguish a pseudoseizure from an epileptic seizure and to
      treat them separately, 3) not to treat seizure phenomena but patients by keeping
      reliable relationship with them.

PMID- 16637588
TI  - [Clinical study on epilepsy and psychosis].
AB  - Several important issues on research in epileptic psychosis are discussed. The
      definition of epileptic psychosis has not been well clarified from
      phenomenological and psychopathological points of view, particularly in
      association with its psychiatric negative symptoms. It is still uncertain whether
      epileptic psychosis is distinct from psychoses due to other neurological
      diseases. A recent trend in its sub classification is to categorize epileptic
      psychosis based on its chronological relation to preceding seizures (postictal
      vs. interictal psychoses) rather than its duration (acute/episodic vs. chronic
      psychoses). While the course and prognosis are crucial to understand the nature
      of epileptic psychosis and determine its treatment, only a few studies have dealt
      with these matters. In order to analyse a variety of epilepsy-related, psychosis
      related and psychosocial factors in a large sample, national and international
      collaboration will be needed. Standardization of our diagnostic and evaluation
      skills should be essential for such multi-institutional studies. Furthermore,
      effects of different public health care systems and socio-economical
      circumstances are associated with the results of studies on epileptic psychosis.

PMID- 16637589
TI  - [Functions of the thalamus in psychiatry: the relationship between the thalamus
      and schizophrenia].
AB  - The thalamus involves two electrophysiological systems of the specific projection
      system and the non-specific projection system. The electrical stimulation of the
      former induces the augmenting response in the cerebral cortex and the same of the
      latter induces the recruiting response in the cortex. The non-specific projection
      system is also known as the diffuse thalamo- cortical projection system and it is
      concerned with the maintenance mechanism of consciousness such as sleep and
      wakefulness. The thalamus is concerned in the higher nervous functions such as
      language, cognition, memory and intelligence. Severe nerve cell loss with
      proliferation of hypertrophic astroglia was found in the association nuclei and
      sensory relay nuclei in the thalami of patients suffering from Creutzfeldt-Jakob
      disease. In the brain imaging study, volume reduction of the thalamus, especially
      of dorsomedial nuclei, degradation of glucose metabolism were observed in the
      thalami of patients with schizophrenia. Carlsson considered schizophrenia as a
      subcortical neurotransmitter imbalance syndrome based on the hypothesis of a
      thalamic filter. Andreasen defined schizophrenia as a misconnection syndrome or
      cognitive dysmetria induced by dysfunction of the cortico-cerebellar-thalamic
      cortical circuit (CCTCC).

PMID- 16637590
TI  - Expression profiling in brain disorders and beyond.
AB  - Large scale expression profiling studies provide a wealth of data that even after
      stratification by sophisticated biostatistical procedures leave the researcher
      more or less puzzled and helpless. This report is meant to encourage molecular
      biologists facing compounding gene lists resulting from expression profiling
      studies to understand them as intellectual challenges that require the
      researchers' solid scientific experience plus a good deal of curiosity. Three
      examples from expression profiling investigations on distinct aspects of brain
      inflammation are covered here. They show that even without good software programs
      it is possible to come up with reasonable biological hypotheses to be evaluated
      in subsequent more detailed experiments.

PMID- 16637591
TI  - [S100B: astrocyte specific protein].
AB  - The S100B is a Ca2+ binding proteins of EF-hand type and is produced primarily by
      astrocytes in the central nervous system. This protein has been implicated in the
      Ca2+-dependent regulation of a variety of intracellular functions such as protein
      phosphorylation, enzyme activities, cell proliferation and differentiation,
      dynamics of cytoskeleton constituents, structural organization of membranes,
      intracellular Ca2+ homeostasis, inflammation, and protection from oxidative cell
      damage. Recent studies suggest that released S100B exerts paracrine and autocrine
      effects on neurons and glia. On the other hand, elevations of S100B levels in
      blood or cerebrospinal fluid have been observed in patients with Alzheimer's
      disease, Down's syndrome, amyotrophic lateral sclerosis, multiple sclerosis,
      schizophrenia, depression, cerebral stroke and traumatic brain injury, and the
      levels have reached micromol/L-order at focal regions. It has been documented
      that the excessive S100B promotes the expression of inducible nitric oxide
      synthase or pro-inflammatory cytokines and exhibits detrimental effects on
      neurons. On studies using some animal models of the cerebral stroke or
      Alzheimer's disease, it is suggested that the excessive S100B produced by
      activated astrocytes precedes neurodegenerations. Authors discussed the
      relationship between neurological disorders and the S100B.

PMID- 16637592
TI  - [Imaging of glial cells by positron-emitted peripheral benzodiazepine receptor
      ligands].
AB  - Recently, it has been indicated that glial cells play as important role in the
      development of neurodegenerative disorders. Expression of peripheral
      benzodiazepine receptor (PBR) has higher localization in the glial cells than in
      the neural cells, and is a noticeable marker for gliosis produced by
      neurodegeneration. In vivo imaging of PBR has been attempted by [11C]PK11195
      positron emission tomography (PET), and it has been documented that the
      [11C]PK11195 binding potential increases in various neurodegenerative disorders
      such as Alzheimer's disease and stroke. Furthermore, we have succeeded in
      developing new positron ligands [11C]DAA1106 and [18F]fluoroethyl-DAA1106 for
      visualization of PBRs, which have higher accumulation in the brain than
      [11C]PK11195. We concluded that PET imaging by PBR ligands is useful for
      diagnosis of neurodegenerative disorders.

PMID- 16637593
TI  - [Abeta, tau and alpha-synuclein and glial cells].
AB  - Many neurodegenerative diseases such as Alzheimer's disease and Parkinson's
      disease are now characterized by abnormal accumulation of certain proteins in the
      brain. The key molecules include amyloid beta-protein (Abeta), tau and a
      synuclein, all of which are involved in the pathogenesis and provide
      histopathological hallmarks of the diseases. Abeta is continuously produced in
      and removed from the brain. Microglia and astrocytes take up and degrade soluble
      Abeta. In the Alzheimer brain, once-deposited, insoluble Abeta is also removed by
      phagocytosis by activated microglia. The success of these removal processes,
      however, is at best partial. The phagocytic removal of insoluble Abeta is
      associated with neuroinflammation, a potentially neurotoxic reaction. Tau is
      accumulated in astrocytes under a diversity of pathological conditions in several
      forms: thorn-shaped astrocytes; tuft-shaped astrocytes; astrocytic plaques. Thorn
      shaped astrocytes are associated with gliosis and are not disease-specific. Tuft
      shaped astrocytes are characteristic of progressive supranuclear palsy (PSP) and
      astrocytic plaques of cortico-basal degeneration (CBD). Tau accumulation in
      oligodendrocytes is referred to as coiled bodies and occurs in PSP, CBD, Pick's
      disease and some other so-called taupathies. a-Synuclein is accumulated in
      oligodendrocytes, which is referred to as glial cytoplasmic inclusions (GCI).
      Occurrence of GCI is diagnostic to multiple system atrophy. Transgenic mouse
      models in which tau or alpha-synuclein is overexpressed in glial cells indicate
      that neuronal degeneration occurs following tau/alpha-synuclein accumulation in
      glial cells, supporting a notion that these abnormal glial cells play pathogenic
      roles.

PMID- 16637594
TI  - [Role of astrocytes in rewarding effects of drugs of abuse].
AB  - There are two categories of cells in the central nervous system; neurons and
      adjacent glial cells including astrocytes, microglia and oligodendrocytes.
      Accumulating evidence suggests that astrocytes actively participate in synaptic
      plasticity. On the other hand, long-term exposure to drugs of abuse could induce
      neuronal plasticity. Astrocytes undergo a process of prolifiration, morphological
      change, and enhancement of glial fibrillary acidic protein expression, termed
      activation of astrocytes. Recently, we demonstrated a dramatic increase in
      reactive astrocytes in the dorsal horn of the spinal cord following repeated in
      vivo treatment with morphine. We also found that in vivo treatment with morphine,
      which was associated with the rewarding effect, caused a robust astrocytic
      activation in the cingulate cortex. These data suggest that astrocytes may
      contribute to the synaptic plasticity induced by morphine during the development
      of dependence and tolerance. Therefore, this review focuses on several aspects of
      astrocytic response and discusses possible roles of astrocytes in the development
      of dependence and tolerance induced by morphine. We also report here that protein
      kinase C, Janus kinase/signal transducer and activator of transcription pathway,
      cyclin-dependent kinase 5 and tyrosine kinase cascade are directly involved in
      the neuron-glia communication during the development of synaptic plasticity
      induced by chronic morphine treatment.

PMID- 16637595
TI  - [Development of a new multidimensional inventory to assess subjective symptoms in
      perimenopause women, using a confirmatory factor analysis].
AB  - The multidimensional inventory is a 60-item self-report instrument designed to
      measure perimenopausal subjective symptoms. It covers the following 5 dimentions:
      sexual function, mental condition, interpersonal anxiety, autonomic balance, and
      the other subjective symptoms. We conducted a survey of perimenopausal subjective
      symptoms in 670 women between 40 and 59 years old, who were living in an urban
      (n=329) or rural area (n=341). The dimensional structure was determined
      statistically using confirmatory factor analysis. The hypothesized five-factor
      model appeared to fit the data in all samples tested, with enough validity
      (RMSEA=0.050, GFI=0.802, and AGFI=0.786). The instrument was found to have
      appropriate internal consistency, with an average Chronbach's alpha coefficient
      of 0.959. There was no significant difference in the severity of subjective
      symptoms between the residential areas. We found a positive correlation between
      the severity of subjective symptoms and the level of stress (urban women:
      r=0.465, P<0.01; rural women: r=0.455, P<0.01). Our findings suggest that the new
      multidimentional inventory may provide a useful instrument for evaluating the
      effect of a drug on subjective symptoms in perimenopausal women.

PMID- 16637596
TI  - Induction of neuroserpin expression in rat frontal cortex after chronic
      antidepressant treatment and electroconvulsive treatment.
AB  - Using expressed sequence tag (EST) analysis, we previously identified certain
      molecular machinery that mediates antidepressant effects. To date, several
      partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been
      isolated as ESTs from rat brain. In the present study, we identified two of the
      ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated
      increased neuroserpin mRNA expression in rat frontal cortex after chronic
      treatment with several classes of antidepressants, including imipramine,
      fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT),
      another therapeutic treatment for depression, also increased neuroserpin
      expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that
      is implicated in the regulation of synaptic plasticity, neuronal migration, and
      axogenesis in the central nervous system. In conclusion, our results support the
      hypothesis that neuroserpin-mediated plastic changes in frontal cortex may
      underlie the therapeutic action of antidepressants and ECT.

PMID- 16637597
TI  - [Role of molecules expressed in spiral microglia in neuropathic pain].
AB  - Physiological pain is an essential experience that alerts us to the presence of
      external or internal stimuli that are damaging or are potentially tissue
      damaging. By contrast, pathological pain is not tied to the presence of tissue
      damaging stimuli. One type of pathological pain-neuropathic pain--is often a
      consequence of nerve injury or of diseases such as diabetes, HIV AIDS or cancer,
      that damage peripheral nerves. Neuropathic pain can be agonizing, persistent over
      long periods, and, unfortunately, is often resistant to known pain-killers.
      Recent advances in our understanding of the mechanisms producing neuropathic pain
      have been made by defining causal roles of spinal microglia in the pathogenesis
      of neuropathic pain as several molecules including P2X4 receptors, which are
      present in activated microglia, have been found to be required molecular
      mediators. We expect that understanding the key roles of these molecules in
      spinal microglia may lead to new strategies for the management of neuropathic
      pain, strategies not previously anticipated by a neuron-centric view of pain
      plasticity in the dorsal horn.

PMID- 16637598
TI  - Design of a protein kinase-inducible domain.
AB  - Protein phosphorylation is a critical regulatory strategy. New tools are
      necessary which may be used to interrogate and are responsive to the activities
      of protein kinases and phosphatases. We have used protein design to develop a
      protein motif, termed a protein kinase-inducible domain, whose structure is
      dependent on its phosphorylation state. Based on an EF hand calcium-binding loop,
      the key design element is the replacement of a structurally critical Glu residue,
      which binds metal in a bidentate manner, with a serine residue, which is expected
      to bind metal tightly when phosphorylated but poorly when not phosphorylated. The
      design comprises an EF hand consensus sequence, a tryptophan at residue 7 to
      sensitize lanthanide luminescence, and the recognition sequence of a
      serine/threonine kinase. Designed peptides, which contain minimal substrate
      recognition motifs of the protein kinases PKA, PKC, or the MAP kinase Erk, form
      complexes with Tb3+ when phosphorylated, showing strong Tb3+ luminescence
      emission at 544 nm, but show weak luminescence when not phosphorylated. The
      change in fluorescence on phosphorylation is comparable to or greater than that
      observed in described kinase sensors. Site-specific lanthanide binding was
      confirmed by NMR with diamagnetic and paramagnetic metals. The kinase-inducible
      domain peptides comprise an expressible sequence, potentially enabling their use
      as genetically encoded tags of protein kinase activity. The motif is general and
      potentially applicable to the majority of serine/threonine kinases.

PMID- 16637599
TI  - Pi-conjugated aromatic enynes as a single-emitting component for white
      electroluminescence.
AB  - By use of the organolanthanide catalysts Me2Si(C5Me4)(NAr)Lu(CH2SiMe3)(THF) and
      (C5Me5)2LaCH(SiMe3)2, carbazole-substituted phenyl enynes (Z)-CPEY and (E)-CPEY
      were synthesized, respectively, with excellent regio- and stereoselectivity
      through the catalytic dimerization of the corresponding terminal alkyne. These
      new pi-conjugated compounds, in particular, the (E)-enyne isomer (E)-CPEY, act as
      an excellent single-emitting component for white organic light-emitting devices
      (WOLEDs), as a result of combination of the blue emission from an isolated
      molecule with the longer-wavelength emissions (green and orange-red) from
      excimers. The (E)-CPEY-based double-layer device emitted almost pure white light
      with CIE coordinates of (0.32, 0.33), maximum brightness of 1395 cd m-2, and
      maximum current efficiency of 2.07 cd A-1. This is perhaps the purest white
      emission ever reported for a single-emitting-component WOLED. The quality of the
      white emission remained almost unchanged under varying driving voltages,
      demonstrating an advantageous potential of single-emitting-component WOLEDs.

PMID- 16637600
TI  - Functionalized surface arrays for spatial targeting of immune cell signaling.
AB  - The effect of surface topography and chemistry on cellular response is of
      fundamental importance, especially where living systems encounter device surfaces
      as in medical implants, tissue engineering, and cell-based sensors. To understand
      these biological processes on surfaces, there is a widespread interest in
      tailored surface-active materials produced by a combination of surface chemistry
      coupled to advanced patterning processes. We utilize self-assembled monolayers
      (SAMs) as molecular templates with submicrometer-scale spatial resolution to
      engage and cluster IgE receptors on rat basophilic leukemia (RBL) mast cells.
      Bioactive templates consisted of gold arrays on silicon with patterns from 1 mum
      down to 45 nm. These gold arrays served as molecular tethering sites, enabling
      covalent binding of functionalized self-assembled monolayers of alkanethiols. The
      free ends of the monolayers were functionalized with 2,4-dinitrophenyl(DNP)
      caproate-based ligands which interact specifically with anti-DNP IgE bound to its
      high affinity cell surface receptor, FcepsilonRI on RBL mast cells. Present
      results on structures 1 mum down to 600 nm in size indicate that these ligand
      immobilized patterned arrays can function as a powerful tool for visualization
      and systematic characterization of cell membrane involvement in IgE receptor
      mediated immune cell signaling.

PMID- 16637601
TI  - Identification of sugar isomers by single-molecule force spectroscopy.
AB  - The nanomechanical properties of beta-galactan, a 1 --> 4 linked beta-d-galactose
      polysaccharide, were investigated with AFM-based single-molecule force
      spectroscopy. AFM captured a unique plateau at 640 pN in the force spectrogram of
      beta-galactan, which is significantly different than the plateau at 280 pN in the
      force spectrogram of amylose. Thus, our results demonstrate that force
      spectroscopy is able to discriminate between sugar isomers in which axial and
      equatorial bonds at C1 and C4 are swapped.

PMID- 16637602
TI  - Rapid freeze-quench ENDOR study of chloroperoxidase compound I: the site of the
      radical.
AB  - The classical heme-monooxygenase active intermediate, compound I (Cpd-I),
      incorporates a heme which is oxidized by two equivalents above the resting ferric
      state, one equivalent associated with a ferryl center, [Fe=O]2+ (FeS = 1), and
      the other with an active-site radical (RS = 1/2). Theoretical calculations on
      models of a Cpd-I with a thiolato axial ligand have presented divergent views
      about its electronic structure. In one picture, the radical is on the porphyrin;
      in the other, it is on the sulfur. In this report, ENDOR spectroscopy answers the
      question, does Cpd-I of the enzyme chloroperoxidase contain a porphyrin pi-cation
      radical or an iron-bound cysteinyl radical: the radical is predominantly on the
      porphyrin, with spin density on sulfur having an upper bound, rhoS </= rhoSmax
      approximately 0.23. We further suggest that the same answer applies to Cpd-I of
      cytochromes P450.

PMID- 16637603
TI  - Enantioselective, facially selective carbomagnesation of cyclopropenes.
AB  - Described is the facially selective and enantioselective addition of carbon
      nucleophiles to prochiral 3-hydroxymethylcyclopropenes. The process creates up to
      four stereocenters in a tandem addition/capture sequence that combines three
      simple materials to give complex and diverse products. The asymmetry is induced
      by the inexpensive and recoverable ligand (S)-N-methylprolinol. The
      enantioselectivity (90-98% ee with MeMgCl) is high for a range of cyclopropenes
      and electrophiles. Importantly, the diastereoselectivity is complementary to that
      obtained by enantioselective cyclopropanation with aryldiazoacetates. High
      enantioselectivities are obtained only when methoxide is included in the
      reaction. Evidence is provided that at least two chiral ligands are involved in
      the enantioselectivity-determining step.

PMID- 16637604
TI  - Use of an electron-reservoir complex together with air to generate N-heterocyclic
      carbenes.
AB  - Imidazolium salts with suitable substituents are readily deprotonated to stable
      NHC carbenes using the electron-reservoir complex [FeICp(eta6-C6Me6)], 1, in the
      presence of air (via a superoxide radical anion acting as a base). Less stable
      NHC carbenes can be conveniently obtained from imidazolium salts using the
      neutral base [FeIICp(eta5-C6Me5CH2)] obtained from 1 and air.

PMID- 16637605
TI  - Stereoselective alkylation of alpha,beta-unsaturated imines via C-H bond
      activation.
AB  - The stereoselective alkylation of alpha,beta-unsaturated imines via C-H
      activation followed by imine hydrolysis produces tri- and tetrasubstituted
      alpha,beta-unsaturated aldehydes. In the presence of a rhodium catalyst,
      alpha,beta-unsaturated N-benzyl imines derived from methacrolein, crotonaldehyde,
      and tiglic aldehyde undergo directed C-H activation at the beta-position and
      react with terminal alkenes and alkynes to form the tri- and tetrasubstituted
      alpha,beta-unsaturated imines with very high stereoselectivity. Hydrolysis to
      provide alpha,beta-unsaturated aldehydes can be performed under carefully
      controlled conditions that maintain the stereochemistry of the beta-alkylated
      imine products. Alternatively, for beta-alkylation products of the N-benzyl imine
      of methacrolein, hydrolysis can be performed under conditions that provide
      complete isomerization to the E isomer.

PMID- 16637606
TI  - Linear aglycones are the substrates for glycosyltransferase DesVII in methymycin
      biosynthesis: analysis and implications.
AB  - The two essential structural components of macrolide antibiotics are the
      polyketide aglycone and the appended sugars. The aglycone formation is catalyzed
      by polyketide synthase (PKS), and glycosylation is catalyzed by an appropriate
      glycosyltransferase. Although it has been shown that glycosylation occurs after
      the cyclic aglycone is released from PKS, it is not known whether the acyl
      carrier protein (ACP)-bound linear polyketide chain can also be processed by the
      corresponding glycosyltransferase. To explore this possibility, the aglycone, 10
      deoxymethynolide, which is the precursor of methymycin and neomethymycin, was
      chemically synthesized in the linear form as a N-acetylcysteamine (NAC)
      thioester. Subsequent incubation with TDP-d-desosamine in the presence of the
      dedicated glycosyltransferase, DesVII, and activator, DesVIII, produces a more
      polar product whose high-resolution mass is consistent with the anticipated
      glycosylated product. This study demonstrated for the first time that a macrolide
      glycosyltransferase can also recognize and process the linear precursor of its
      macrolactone substrate with a reduced but measurable activity.

PMID- 16637607
TI  - Thermal isomerizations of 2-d-1-(E)-propenylcyclobutanes to 4-d-3
      methylcyclohexenes.
AB  - Racemic trans-2-d-1-(E)-propenylcyclobutane at 276 degrees C in the gas phase
      fragments to give ethylenes and pentadienes, equilibrates with its cis isomer,
      and rearranges to mixtures of 4-d- and 6-d-3-methylcyclohexenes through [1,3]
      carbon shifts. The time-dependent distributions of deuterium-labeled isomers of
      propenylcyclobutanes and 3-methylcyclohexenes reveal a significant secondary
      deuterium kinetic isotope effect favoring C1-C4 over C1-C2 bond breaking (kH/kD =
      1.16 +/- 0.02) and a 72:28 preference for structural isomerizations giving (si +
      ar) rather than (sr + ai) products through conformationally flexible short-lived
      diradical intermediates.

PMID- 16637608
TI  - Li+-catalyzed radical polymerization of simple terminal alkenes.
AB  - Solutions of Li+ salts of highly alkylated derivatives of the
      monocarbadodecaborate anion in 1,2-dichloroethane catalyze the radical
      polymerization of simple terminal alkenes, dienes, and alkynes under ambient
      conditions, initiated by azoisobutyronitrile, di-tert-butyl peroxide, or
      atmospheric air.

PMID- 16637609
TI  - Metallic polycrystalline thin films of the single-component neutral molecular
      solid Ni(tmdt)2.
AB  - Metallic thin films of the single-component, neutral, molecular solid Ni(tmdt)2
      have been prepared by electrocrystallization on passivated silicon substrates.
      Metallicity is achieved down to 6 K despite the polycrystalline morphology.

PMID- 16637610
TI  - A simple numerical calculation correctly predicts the observed size regime for
      growth of tetrapodal chalcogenide nanocrystals.
AB  - Synthetic schemes yielding monodisperse nanocrystalline particulates in the form
      of tetrapods, rods, and prisms have been recently discovered. Conditions
      promoting growth of different shapes of particulates have been defined. However,
      the rationale for anisotropic growth and the evolution of specific shapes, such
      as tetrapods, is as yet unknown. On the basis of simple numerical calculations,
      we suggest that the need to conserve the surface atoms plays a vital role in the
      growth of nanocrystals in the formation of tetrapods and correctly predicts the
      size regime in which such structures are obtained.

PMID- 16637611
TI  - A selective activity-based probe for the papain family cysteine protease
      dipeptidyl peptidase I/cathepsin C.
AB  - Dipeptidyl peptidase I is involved in the activation of a number of disease
      related proteases by removal of N-terminal prodipeptides. We here report a
      selective activity-based probe for monitoring dipeptidyl peptidase I activity in
      whole proteomes as well as in intact cells, without labeling of closely related
      enzyme family members.

PMID- 16637612
TI  - Diphenylmethane-mediated transmethylation of methylbenzenes over H-zeolites.
AB  - Despite their vital roles in the catalytic cycle for toluene disproportionation,
      diphenylmethane (DPM)-type compounds have never been directly detected or proved
      to be true reaction intermediates from experimental techniques. In this report,
      we provide unprecedented insights into the DPM-mediated reaction mechanism, by
      demonstrating the build-up of DPM species inside the zeolite pores and following
      their decomposition. It can be stated that, despite their bulkiness,
      (di)methylated DPM species may indeed be formed at high concentrations in the ZSM
      5 channels when toluene is reacted. The dimethyl-DPM species are unstable when
      present in the zeolite voids and decompose under a concomitant evolution of
      xylene at 200 degrees C.

PMID- 16637613
TI  - All-carbon quaternary centers via catalytic asymmetric hydrovinylation. New
      approaches to the exocyclic side chain stereochemistry problem.
AB  - 1-Alkylstyrenes undergo efficient hydrovinylation (coupling with ethylene) in the
      presence of 1 mol % of a Ni catalyst prepared from [(allyl)NiBr]2, Na+BAr4- (Ar =
      3,5-bistrifluoromethylphenyl), and phosphoramidite ligands (derived from
      enantiopure binaphthols and 1-methylbenzylamines), giving hydrovinylation
      products in excellent yields and enantioselectivities. The products contain a
      quaternary center with two versatile latent functionalities, an arene and a vinyl
      group, useful for further synthetic elaborations.

PMID- 16637614
TI  - Directing the growth of highly aligned gold nanorods through a surface chemical
      amidation reaction.
AB  - This paper describes the seed-mediated growth of highly aligned gold nanorods (Au
      NRs) over large areas directly on a Si(100) surface. The Si(100) surface is NH2
      functionalized with (aminopropyl)triethoxysilane (APTES) followed by a DCC
      catalyzed surface amidation reaction with acetic acid. After exposure to a gold
      nanoparticle (Au NP) "seed" solution, chemical seed-mediated growth of the
      surface-bound seeds via reduction of AuCl4- by ascorbic acid in the presence of
      cetyltrimethylammonium bromide leads to the growth of highly aligned Au NRs on
      the surface. About 80% of the NRs are aligned in the same direction within a +/
      30 degrees range. Au NRs account for 19% of the nanostructures with average
      aspect ratio (AR) of approximately 20. The alignment direction did not correlate
      with the atomic arrangement of the Si(100) crystal since it varied over different
      regions of the sample, rotating by 90 degrees from top to bottom of an
      approximately 5 mm sample. Si crystallinity may still be important since
      alignment is not observed on amorphous glass. Surface functionalization is the
      key since alignment is only observed following the amidation reaction and not on
      NH2-functionalized, SH-functionalized, or bare Si(100) surfaces. Alignment also
      occurred for Au NRs grown on Si(100)/APTES reacted with succinic acid and on Ag
      NRs grown on Si(100)/APTES/acetic acid surfaces. This unique alignment of metal
      NRs promoted by a surface amidation chemical reaction may find use in
      nanoelectronics, chemical sensing, and plasmonics applications.

PMID- 16637615
TI  - Catalytic enantioselective synthesis of chiral phthalides by SmI2-mediated
      reductive cyclization of 2-acylarylcarboxylates.
AB  - A significant new and efficient catalytic asymmetric approach for the highly
      enantioselective synthesis of chiral phthalides by SmI2-induced reductive
      cyclization of 2-acylarylcarbonylates was developed. The combination of (4S,5R)
      4,5-diphenyloxazolidin-2-one and 2,2,6,6-tetramethylpiperidine was found to be a
      very effective catalyst system in the reaction. This method provides a ready
      access to a broad range of enantiomerically enriched phthalides (up to 99% ee).

PMID- 16637616
TI  - Sugar-assisted glycopeptide ligation.
AB  - The chemical synthesis of glycopeptides and glycoproteins from readily available
      materials presents an attractive route to homogeneous products for structural and
      functional studies. Chemical synthesis of glycopeptides and glycoproteins based
      on native chemical ligation represents one of the useful methods for the
      synthesis of natural glycopeptide structures. Here we describe a method that
      allows for the synthesis of glycopeptides from cysteine-free peptides. This
      method utilizes a peptide thioester and a glycopeptide in which the sugar moiety
      is modified with a thiol handle at the C-2 position. Upon completion of the
      ligation reaction, the thiol handle can be reduced with H2/metal to the acetamide
      moiety, furnishing the unmodified glycopeptides. Together, this sequence of
      reactions displays an attractive potential in glycopeptides and glycoproteins
      synthesis.

PMID- 16637617
TI  - Rhodium-catalyzed asymmetric construction of quaternary carbon stereocenters:
      ligand-dependent regiocontrol in the 1,4-addition to substituted maleimides.
AB  - A rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to substituted
      maleimides has been described. The regioselectivity in this reaction is
      controlled by the choice of ligand (dienes or bisphosphines), and 1,4-adducts
      with a quaternary stereocenter can be obtained with high regio- and
      enantioselectivity by the use of (R)-H8-binap.

PMID- 16637618
TI  - Palmerolide A, a cytotoxic macrolide from the antarctic tunicate Synoicum
      adareanum.
AB  - Palmerolide A, a 20-membered macrocyclic polyketide bearing carbamate and vinyl
      amide functionality, was isolated from the tunicate Synoicum adareanum collected
      from the vicinity of Palmer Station on the Antarctic Peninsula. Palmerolide A
      displays potent and selective cytotoxicity toward melanoma (UACC-66 LC50 = 0.018
      muM) and appears to operate via inhibition (IC50 = 2 nM) of V-ATPase.

PMID- 16637619
TI  - Low-temperature solution-phase synthesis of quantum well structured CdSe
      nanoribbons.
AB  - Quantum well structured CdSe nanoribbons with uniform and ultrathin thickness of
      1.4 nm were synthesized from the low-temperature reaction of CdCl2 and ammonium
      selenocarbamate. The CdSe nanoribbons exhibited an extremely narrow
      photoluminescence band with fwhm of 70 meV.

PMID- 16637620
TI  - Density functional theory analysis of carboxylate-bridged diiron units in two
      dimensional metal-organic grids.
AB  - Carboxylate-bridged diiron units have been realized recently in two dimensions
      via metal-directed self-assembly of simple organic linkers. They represent
      notably a coupling motif stabilizing a series of nanoporous metal-organic
      coordination networks and are reminiscent of catalytically active sites in
      metalloproteins. To rationalize their atomic structure, chemical bonding, and
      electronic properties, we performed density functional theory calculations for
      exemplary Fe-terephthalate grids assembled on the Cu(100) surface. The obtained
      atomistic description and understanding is decisive for the considerate use of
      two-dimensional metal-organic coordination networks as templates, guest systems,
      or catalysts.

PMID- 16637621
TI  - Hydride transfer versus hydrogen radical transfer in thymidylate synthase.
AB  - The nature of a H-transfer in the thymidylate synthase catalyzed reaction was
      investigated by comparison of the wild-type enzyme with the W80M mutant. The
      nature of the H-transfer was not affected, as indicated by intrinsic isotope
      effects and their temperature dependence. These findings support a single-step
      hydride transfer instead of a two-step radical transfer.

PMID- 16637622
TI  - Orientation of a key glutamine residue in the BLUF domain from AppA revealed by
      mutagenesis, spectroscopy, and quantum chemical calculations.
AB  - The flavin-adenine-dinucleotide-binding BLUF domain constitutes a new class of
      blue-light receptors, and the N-terminal domain of AppA is a representative of
      this family. A crystal structure of the BLUF domain from AppA suggested that a
      conserved Gln63 forms a hydrogen bond with the flavin N5 atom. Upon light
      excitation, this residue is proposed to undergo a approximately 180 degrees
      rotation that leads to a rearrangement of a hydrogen bonding network. However,
      crystallographic studies on the other BLUF proteins claimed an opposite
      orientation for the glutamine residue. In this communication, we have revealed
      the presence of a Gln63-to-N5 hydrogen bond in the dark state of AppA by a
      combined approach of mutagenesis, spectroscopy, and quantum chemical
      calculations. The present finding supports the view that the reorientation of the
      Gln63 side chain is a key event in the signaling state formation of BLUF
      proteins.

PMID- 16637623
TI  - Cross-reactive conjugated polymers: analyte-specific aggregative response for
      structurally similar diamines.
AB  - A single cross-reactive conjugated polymer (poly(thiophene) 1) generates unique
      spectral patterns in response to structurally similar diamines. Multivariate
      statistics are used to deconvolute subtle variations in these spectral responses,
      allowing for identification and quantification of the analytes with >99%
      accuracy.

PMID- 16637624
TI  - Synthesis and biological activity of phospholipase C-resistant analogues of
      phosphatidylinositol 4,5-bisphosphate.
AB  - The membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
      is an important regulator in cell physiology. Hydrolysis of PtdIns(4,5)P2 by
      phospholipase C (PLC) releases two second messengers, Ins(1,4,5)P3 and
      diacylglycerol. To dissect the effects of PtdIns(4,5)P2 from those resulting from
      PLC-generated signals, a metabolically stabilized analogue of PtdIns(4,5)P2 was
      required. Two analogues were designed in which the scissile O-P bond was replaced
      with a C-P bond that could not be hydrolyzed by PLC activity. Herein we describe
      the asymmetric total synthesis of the first metabolically stabilized
      phospholipase C-resistant analogues of PtdIns(4,5)P2. The key transformation was
      a Pd(0)-catalyzed coupling of a H-phosphite with a vinyl bromide to form the
      desired C-P linkage. The phosphonate analogues of PtdIns(4,5)P2 were found to be
      effective in restoring the sensitivity of the TRPM4 channel to Ca2+ activation.

PMID- 16637625
TI  - Direct synthesis of a metalloporphyrin complex on a surface.
AB  - We demonstrate that well-defined monolayers of a metal complex on a surface can
      be prepared by direct vapor deposition of the metal atoms on monolayers of the
      ligand. In particular, ordered monolayers of adsorbed tetraphenylporphyrin (2H
      TPP) on a silver surface were exposed to cobalt vapors, resulting in the
      complexation of the metal by the porphyrin. The formation of the metal complexes
      was monitored by means of X-ray photoelectron spectroscopy (XPS), which reveals
      that this metalation reaction leads to a chemical equivalence of all four
      nitrogen atoms. The described in situ metalation provides a convenient way to
      produce adsorbed monolayers of more reactive (e.g., air- or solvent-sensitive) or
      thermally unstable metalloporphyrins that are difficult to evaporate or even to
      obtain as pure compounds at room temperature.

PMID- 16637626
TI  - Synthesis of the pyrazolo[4,3-e][1,2,4]triazine family of natural products:
      nostocine A, fluviol A, and pseudoiodinine.
AB  - The first syntheses of any members of the naturally occurring pyrazolo[4,3
      e][1,2,4]triazine family are reported, verifying the structures of nostocine A
      and fluviol A, and leading to the revision of the structure of pseudoiodinine.
      The revised structure of pseudoiodinine was also established by total synthesis.

PMID- 16637627
TI  - The oxidative mannich reaction catalyzed by dirhodium caprolactamate.
AB  - Dirhodium caprolactamate [Rh2(cap)4] is a highly effective catalyst for the
      oxidative Mannich reaction. The reaction proceeds via C-H oxidation of a tertiary
      amine followed by nucleophilic capture. This green transformation is conducted in
      protic solvent using inexpensive T-HYDRO (70% t-BuOOH in water). Synthetically
      valuable gamma-aminoalkyl butenolides are obtained.

PMID- 16637628
TI  - Two-dimensional surface chirality control by solvent-induced helicity inversion
      of a helical polyacetylene on graphite.
AB  - We report the direct evidence for the macromolecular helicity inversion of a
      helical poly(phenylacetylene) bearing l- or d-alanine pendants with a long alkyl
      chain in different solvents by atomic force microscopy observations of the
      diastereomeric helical structures. The diastereomeric helical
      poly(phenylacetylene)s induced in polar and nonpolar solvents self-assembled into
      ordered, two-dimensional helix bundles with controlled molecular packing, helical
      pitch, and handedness on graphite upon exposure of each solvent. The
      macromolecular helicity deposited on graphite from a polar solvent further
      inverted to the opposite handedness by exposure to a specific nonpolar solvent,
      and these changes in the surface chirality based on the inversion of helicity
      could be visualized by atomic force microscopy with molecular resolution, and the
      results were quantified by X-ray diffraction of the oriented liquid crystalline,
      diastereomeric helical polymer films.

PMID- 16637629
TI  - Pattern-based discrimination of enantiomeric and structurally similar amino
      acids: an optical mimic of the mammalian taste response.
AB  - This manuscript describes an optical enantioselective pattern-based sensing
      array. A differential array of enantioselective indicator displacement assays was
      constructed and used to demonstrate simultaneous discrimination of enantiomeric
      and structurally similar alpha-amino acids. Interpretation of the output patterns
      by principle component analysis leads to the separation of enantio- and
      chemoselective information along orthogonal variance axes when chiral receptors
      of opposite enantiomeric preference are included. A general principle is
      delineated that correlates array design with the achievement of enantiomeric
      discrimination analogous to the mammalian gustation response to the amino acids.

PMID- 16637630
TI  - A mismatch-selective bifunctional rhodium-Oregon Green conjugate: a fluorescent
      probe for mismatched DNA.
AB  - A fluorescent metallointercalator conjugate that selectively targets DNA base
      mismatches has been synthesized by coupling an organic fluorophore to a bulky Rh
      intercalator containing the chrysenequinone diimine ligand. Ion pairing between
      the cationic Rh and anionic fluorophore moieties dramatically quenches the
      fluorescence of the conjugate in solution and in the presence of matched DNA.
      However, in the presence of mismatched DNA, the fluorescence of the conjugate is
      increased >300%. This increase in fluorescence is attributed to the loss in
      intramolecular quenching associated with DNA binding; intercalation of the Rh
      moiety into the mismatched site can lead to electrostatic repulsion of the
      anionic fluorophore away from the DNA phosphate backbone and Rh. Denaturing PAGE
      experiments with 32P-labeled oligonucleotides indicate that the conjugate
      selectively binds the mismatched DNA with a binding affinity of 6 x 105 M-1 and,
      upon irradiation, cleaves the DNA backbone neighboring the mismatched site.

PMID- 16637631
TI  - Controlled microfluidic encapsulation of cells, proteins, and microbeads in lipid
      vesicles.
AB  - Cells have been encapsulated inside lipid vesicles by using a new microfluidic
      lipid vesicle formulation technique. Lipid vesicles are formulated within minutes
      without using toxic lipid solvents. The encapsulation efficiency inside the
      vesicles is controlled by the microfluidic flows. Green fluorescent proteins
      (GFP), carcinoma cells, and bead encapsulated vesicles have mean diameters of
      27.2 mum, 62.4 mum, and 55.9 mum, respectively. The variations of vesicle sizes
      are approximately 20% for the GFP and cell encapsulated vesicles and
      approximately 10% for the bead encapsulated vesicles.

PMID- 16637632
TI  - Protein-cofactor interactions and EPR parameters for the Q(H) quinone binding
      site of quinol oxidase. A density functional study.
AB  - Recent multifrequency EPR studies of the "high-affinity" quinone binding site of
      quinol oxidase (Q(H) site) have suggested a very asymmetric hydrogen-bonding
      environment for the semiquinone radical anion state. Single-sided hydrogen
      bonding to the O1 carbonyl position was one of the proposals, which contrasts
      with some previous experimental indications. Here density functional calculations
      of the EPR parameters (g-tensors, 13C, 1H, and 17O hyperfine tensors) for a wide
      variety of supermolecular model complexes have been used to provide insight into
      the detailed relations among structure, environment, and EPR parameters of
      ubisemiquinone radical anions. A single-sided binding model is not able to
      account for the experimentally observed low g(x) component of the g-tensor or for
      the observed magnitude of the asymmetry of the 13C carbonyl HFC tensors. Based on
      the detailed comparison between computation and experiment, a model with two
      hydrogen bonds to O1 and one hydrogen bond to O4 is suggested for the Q(H) site,
      but a model with one more hydrogen bond on each side cannot be excluded. Several
      general conclusions on the interrelations between EPR parameters and hydrogen
      bond patterns of ubisemiquinones in proteins are provided.

PMID- 16637633
TI  - Two-dimensional self-assembly of 1-pyrylphosphonic acid: transfer of stacks on
      structured surface.
AB  - Strong hydrogen bonding and pi-pi stacking between 1-pyrylphosphonic acid (PYPA)
      molecules were exploited to create self-assembled two-dimensional supramolecular
      structures. Polycrystalline films of these laminate crystalline PYPA bilayers
      were easily deposited onto the solid supports through a simple spin-coating
      technique. Atomic force microscopy (AFM), scanning tunneling microscopy (STM), X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), UV-vis
      absorption, and fluorescence spectroscopy reveal that processing parameters, such
      as solvent, concentration, and surface of the substrate, are critical factors in
      determining the final morphology of the stacked film. Robust laminate structures
      could be obtained only when short alkyl chain protic solvents (methanol or
      ethanol) and a nonhydrophobic substrate surface were used. Polycrystalline films
      were formed through the nucleation and growth of PYPA molecules into laminate
      structures at the air/solvent interface before they land on the substrate during
      the spin-coating process. These films possess good mechanical properties and were
      easily transferred onto a SiO2/Si substrate that was patterned with Au electrodes
      without breaking their crystalline structures. The successful transfer of the
      laminate crystals allows us to probe their electrical properties through a field
      effect transistor device. A gating effect on the charge transport of the stacked
      films indicates that PYPA laminate crystal possesses p-typed semiconductor
      characteristics.

PMID- 16637634
TI  - Air-Initiated Radical Polymerization of Lithium Salts of omega-(Undecamethylcarba
      closo-dodecaboran-1'-yl)alk-1-enes, CH2=CH(CH2)(n-2)C(BMe)11- Li+.
AB  - We report an easy access to the salts of the LiC(BMe)11- anion, which greatly
      simplifies the synthesis of compounds carrying the -C(BMe)11- substituent,
      including the title anions. The previously recognized and puzzling spontaneous
      oligomerization of the solid lithium salts CH2=CH(CH2)(n-2)C(BMe)11- Li+ upon
      storage under ambient conditions is now shown to proceed by a radical mechanism,
      with the "naked" Li+ cation acting as a catalyst. The degree of polymerization is
      higher in solution, especially when azoisobutyronitrile (AIBN) is used as
      initiator (up to approximately 50). Initiation by the thermal decomposition of
      AIBN is also catalyzed by naked Li+, and this initiator is effective at room
      temperature. Di-tert-butyl peroxide and UV irradiation can also be used. The
      observation of Li+ catalysis agrees with a prior prediction from ab initio
      calculations, according to which Li+ complexation of ethylene strongly lowers the
      activation energy for methyl radical addition. The results bear on the current
      discussion of the possible sensitivity of radical clocks to their molecular
      environment and suggest that naked Li+ will catalyze the radical polymerization
      of simple terminal alkenes.

PMID- 16637635
TI  - Molecular motion of tethered molecules in bulk and surface-functionalized
      materials: a comparative study of confinement.
AB  - Achieving high degrees of molecular confinement in materials is a difficult
      synthetic challenge that is critical for understanding supramolecular chemistry
      on solid surfaces and control of host-guest complexation for selective adsorption
      and heterogeneous catalysis. In this Article, using 2H MAS NMR spectroscopy of
      tethered carbamates as a molecular probe, we systematically investigate the
      degree of steric confinement within three types of materials: two-dimensional
      silica surface, bulk amorphous microporous silica, and bulk amorphous mesoporous
      silica. The resulting NMR spectra are described with a simple two-site hopping
      model for motion and prove that the bulk silica network severely limits the
      molecular mobility of the immobilized carbamate at room temperature to the same
      degree as surface-functionalized materials at low-temperatures (approximately 210
      K). Raising the temperature of the bulk materials to 413 K still demonstrates the
      effect of confinement, as manifested in significantly longer characteristic times
      for the immobilized carbamate relative to surface-functionalized materials at
      room temperature. The environment surrounding the carbonyl functionality of the
      immobilized carbamate is investigated using FT-IR spectroscopy, which shows the
      carbonyl stretching band to be equally shifted for all materials to lower
      wavenumbers relative to its noninteracting value in carbon tetrachloride solvent.
      These results suggest that electrostatic interactions between the carbonyl of the
      immobilized carbamate and silica surface may play an important role in confining
      the immobilized carbamate and nucleating the formation of a pore wall close to
      the immobilized carbamate during bulk materials synthesis.

PMID- 16637636
TI  - Mechanism of thio acid/azide amidation.
AB  - A combined experimental and computational mechanistic study of amide formation
      from thio acids and azides is described. The data support two distinct
      mechanistic pathways dependent on the electronic character of the azide
      component. Relatively electron-rich azides undergo bimolecular coupling with
      thiocarboxylates via an anion-accelerated [3+2] cycloaddition to give a
      thiatriazoline. Highly electron-poor azides couple via bimolecular union of the
      terminal nitrogen of the azide with sulfur of the thiocarboxylate to give a
      linear adduct. Cyclization of this intermediate gives a thiatriazoline.
      Decomposition to amide is found to proceed via retro-[3+2] cycloaddition of the
      neutral thiatriazoline intermediates. Computational analysis (DFT, 6-31+G(d))
      identified pathways by which both classes of azide undergo [3+2] cycloaddition
      with thio acid to give thiatriazoline intermediates, although these paths are
      higher in energy than the thiocarboxylate amidations. These studies also
      establish that the reaction profile of electron-poor azides is attributable to a
      prior capture mechanism followed by intramolecular acylation.

PMID- 16637637
TI  - Characterization of lysine-guanine cross-links upon one-electron oxidation of a
      guanine-containing oligonucleotide in the presence of a trilysine peptide.
AB  - Formation of DNA-protein cross-links involving the initial formation of a guanine
      radical cation was investigated. For this purpose, riboflavin-mediated
      photosensitization of a TGT oligonucleotide in aerated aqueous solution in the
      presence of the KKK tripeptide was performed. We have shown that the nucleophilic
      addition of the epsilon-amino group of the central lysine residue of KKK to the
      C8 atom of either the guanine radical cation or its deprotonated form gives rise
      to the efficient formation of a Nepsilon-(guanin-8-yl)-lysine cross-link.
      Interestingly, the time course of formation of the above-mentioned cross-link was
      found to be not linear with the time of irradiation, and its formation rapidly
      reached a plateau. This is explained by secondary decomposition of the initially
      generated cross-link which could be further oxidized more efficiently than
      starting TGT oligonucleotide. One-electron oxidation of the initially generated
      cross-link was found to produce mainly two diastereomeric cross-links exhibiting
      a spiroimino-trilysine-dihydantoin structure as inferred from enzymatic
      digestion, CD, UV, NMR and mass spectrometry measurements. In addition, other
      minor cross-links, for which formation was favored at acidic pH, were assigned as
      lysine-guanine adducts in which the modified guanine base exhibits a guanidino
      trilysine-iminohydantoin structure. A proposed mechanism for the formation of the
      different detected oligonucleotide-peptide cross-links is given. The high yield
      of formation of the detected cross-links strongly suggests that a DNA-protein
      cross-link involving a lysine residue linked to the C8 position of guanine could
      be generated in cellular systems if a lysine is located in the close vicinity of
      a guanine radical cation.

PMID- 16637638
TI  - Evidence for resonance optical trapping of individual fluorophore-labeled
      antibodies using single molecule fluorescence spectroscopy.
AB  - We report single molecule fluorescence studies of the diffusion of individual
      multiple fluorophore-labeled antibodies in solution, which show that a trapping
      potential of about 3.6 k(B)T can be obtained at laser powers below 1 mW with
      resonant excitation. Individual antibodies can be trapped for up to 140 ms, and
      bound antibodies can also be used to trap a single virion for up to 1 s.
      Selective resonance trapping to sort and manipulate fluorophore-labeled
      biomolecules and complexes may be possible.

PMID- 16637639
TI  - Functional dynamics of human FKBP12 revealed by methyl 13C rotating frame
      relaxation dispersion NMR spectroscopy.
AB  - Transverse relaxation dispersion NMR spectroscopy can provide atom-specific
      information about time scales, populations, and the extent of structural
      reorganization in proteins under equilibrium conditions. A method is described
      that uses side-chain methyl groups as local reporters for conformational
      transitions taking place in the microsecond regime. The experiment measures
      carbon nuclear spin relaxation rates in the presence of continuous wave off
      resonance irradiation, in proteins uniformly enriched with 13C, and partially
      randomly labeled with 2H. The method was applied to human FK-506 binding protein
      (FKBP12), which uses a common surface for binding substrates in its dual role as
      both an immunophilin and folding assistant. Conformational dynamics on a time
      scale of approximately 130 micros were detected for methyl groups located in the
      substrate binding pocket, demonstrating its plasticity in the absence of
      substrate. The spatial arrangement of affected side-chain atoms suggests that
      substrate recognition involves the rapid relative movement of the subdomain
      comprising residues Ala81-Thr96 and that the observed dynamics play an important
      role in facilitating the interaction of this protein with its many partners,
      including calcineurin.

PMID- 16637640
TI  - Thermodynamics of formation of host-guest supramolecular polymers.
AB  - The interactions between three beta-cyclodextrin hosts (having 1-3 binding sites)
      and two adamantyl guests (having 1-2 binding sites) have been studied by ITC,
      ROESY, static and dynamic light scattering (SLS and DLS), and AFM and TEM
      techniques. The enthalpy and free energy values (determined from ITC experiments)
      evidence that the single interaction between one binding site of the guest and
      one binding site of the host is independent of the number of binding sites of the
      interacting species. The average values are deltaH degrees = -26.6 +/- 2.3 kJ
      mol(-1) and deltaG degrees = -30.4 +/- 3.2 kJ mol(-1), indicating that the
      process is mainly enthalpy driven. In all cases, the experimental molar ratio
      (from ITC experiments) agrees with the expected one from the number of binding
      sites of both the host and guest. The formation of polymer-like entities was
      demonstrated by SLS, DLS, AFM, and TEM measurements. The structure of polymers is
      linear when both the host and the guest are ditopic entities and dendritic (or
      Cayley tree type) when the host and the guest have three and two binding sites,
      respectively.

PMID- 16637641
TI  - A strategy for the analysis of chiral polyoxotungstates by multinuclear (31P,
      183W) NMR spectroscopy applied to the assignment of the 183W NMR spectra of
      alpha1-[P2W17O61]10- and alpha1-[YbP2W17O61]7-.
AB  - This paper describes the complete assignment of the 183W NMR spectra of the
      chiral polyoxometalates alpha1-[P2W17O61]10- and alpha1-[YbP2W17O61]7- in aqueous
      solution. These spectra display each 17 lines of equal intensity with a
      relatively narrow chemical shift distribution. The identification of signals is
      based on selective 31P-183W decoupling and recognition of particular sets of
      coupling constants for tungsten atoms around the lacunary site. Further
      assignment is obtained by 183W 2D-COSY NMR experiments. We demonstrate herewith a
      new way for the unambiguous assignment of 183W NMR spectra of polyoxotungstates
      without any symmetry elements or tungsten atoms in special positions. This way
      relies on the correlation of the magnitude of 2J(W-W) coupling constants with the
      geometry of oxo-bridges in polyoxotungstates. These results open the way to
      monitor interaction sites of chiral polyoxotungstates with organic ligands.

PMID- 16637642
TI  - Self-assembled monolayers on Pt(111): molecular packing structure and strain
      effects observed by scanning tunneling microscopy.
AB  - Self-assembled monolayers (SAMs) of octanethiol and benzeneethanethiol were
      deposited on clean Pt(111) surfaces in ultrahigh vacuum (UHV). Highly resolved
      images of these SAMs produced by an in situ scanning tunneling microscope (STM)
      showed that both systems organize into a super-structure mosaic of domains of
      locally ordered, closely packed molecules. Analysis of the STM images indicated a
      (square root 3 x square root 3)R30 degrees unit cell for the octanethiol SAMs and
      a 4(square root 3 x square root 3)R30 degrees periodicity based on 2 x 2 basic
      molecular packing for the benzeneethanethiol SAMs under the coverage conditions
      investigated. SAMs on Pt(111) exhibited differences in molecular packing and a
      lower density of disordered regions than SAMs on Au(111). Electron transport
      measurements were performed using scanning tunneling spectroscopy.
      Benzeneethanethiol/Pt(111) junctions exhibited a higher conductance than
      octanethiol/Pt(111) junctions.

PMID- 16637643
TI  - A new reverse wormlike micellar system: mixtures of bile salt and lecithin in
      organic liquids.
AB  - We report a new route for forming reverse wormlike micelles (i.e., long, flexible
      micellar chains) in nonpolar organic liquids such as cyclohexane and n-decane.
      This route involves the addition of a bile salt (e.g., sodium deoxycholate) in
      trace amounts to solutions of the phospholipid lecithin. Previous recipes for
      reverse wormlike micelles have usually required the addition of water to induce
      reverse micellar growth; here, we show that bile salts, due to their unique
      "facially amphiphilic" structure, can play a role analogous to that of water and
      promote the longitudinal aggregation of lecithin molecules into reverse micellar
      chains. The formation of transient entangled networks of these reverse micelles
      transforms low-viscosity lecithin organosols into strongly viscoelastic fluids.
      The zero-shear viscosity increases by more than 5 orders of magnitude, and it is
      the molar ratio of bile salt to lecithin that controls the viscosity enhancement.
      The growth of reverse wormlike micelles is also confirmed by small-angle neutron
      scattering (SANS) experiments on these fluids.

PMID- 16637644
TI  - Non-uniformly sampled double-TROSY hNcaNH experiments for NMR sequential
      assignments of large proteins.
AB  - The initial step of protein NMR resonance assignments typically identifies the
      sequence positions of 1H-15N HSQC cross-peaks. This is usually achieved by
      tediously comparing strips of multiple triple-resonance experiments. More
      conveniently, this could be obtained directly with hNcaNH and hNcocaNH-type
      experiments. However, in large proteins and at very high fields, rapid transverse
      relaxation severely limits the sensitivity of these experiments, and the limited
      spectral resolution obtainable in conventionally recorded experiments leaves many
      assignments ambiguous. We have developed alternative hNcaNH experiments that
      overcome most of these limitations. The TROSY technique was implemented for
      semiconstant time evolutions in both indirect dimensions, which results in
      remarkable sensitivity and resolution enhancements. Non-uniform sampling in both
      indirect dimensions combined with Maximum Entropy (MaxEnt) reconstruction enables
      such dramatic resolution enhancement while maintaining short measuring times.
      Experiments are presented that provide either bidirectional or unidirectional
      connectivities. The experiments do not involve carbonyl coherences and thus do
      not suffer from fast chemical shift anisotropy-mediated relaxation otherwise
      encountered at very high fields. The method was applied to a 300 microM sample of
      a 37 kDa fragment of the E. coli enterobactin synthetase module EntF, for which
      high-resolution spectra with an excellent signal-to-noise ratio were obtained
      within 4 days each.

PMID- 16637645
TI  - High-resolution terahertz spectroscopy of crystalline trialanine: extreme
      sensitivity to beta-sheet structure and cocrystallized water.
AB  - High-resolution terahertz absorption spectra (0.06-3 THz) have been obtained at
      4.2 K for three crystalline forms of trialanine [H2+-(Ala)3-O-]. The crystal
      structures differ in their beta-sheet forms (parallel vs antiparallel) and in
      their water composition (hydrated vs dehydrated antiparallel beta-sheet). The
      spectra are nearly vibrationally resolved, with little absorption below 1 THz. In
      sharp contrast to observations made in the mid-IR region, the spectral patterns
      of all three forms are qualitatively different, illustrating the extreme
      sensitivity to changes in the intermolecular hydrogen-bonding networks that
      stabilize peptide crystals. Predictions obtained from a classical force field
      model (CHARMM) and density functional theory (DFT/PW91) for periodic solids are
      compared with the X-ray structural data and the terahertz absorption spectra. In
      general, the results for the parallel beta-sheet are in better agreement with
      experiment than those for the antiparallel beta-sheet. For all three structures,
      however, most hydrogen bond distances are underestimated at both levels of
      theory, and the predicted absorption features are significantly red-shifted for
      the two antiparallel beta-sheet structures. Moreover, the nuclear motions
      predicted at the two levels of theory are qualitatively different. These results
      indicate that the PW91 functional is not sufficient to treat the weak intersheet
      hydrogen bonding present in the different beta-sheet forms and strongly suggest
      the need for improved force field models that include three-atom hydrogen-bonding
      terms for periodic solids.

PMID- 16637646
TI  - Solution structures of human LL-37 fragments and NMR-based identification of a
      minimal membrane-targeting antimicrobial and anticancer region.
AB  - To understand the structure and activity relationship of human LL-37, a series of
      peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not
      active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as
      well as drug-sensitive and drug-resistant cancer cells. A 13-residue core
      antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37,
      was identified based on total correlated spectroscopy by trimming nonessential
      regions (TOCSY-trim). Because LL-37 acts on bacterial membranes, three
      dimensional structures of its fragments were determined in micelles by NMR,
      including structural refinement by natural abundance 15N and 13C chemical shifts.
      Aromatic-aromatic interactions in the N-terminal fragment were proposed to be
      essential for LL-37 aggregation. The LL-37 core peptide adopts a similar
      structure in the micelles of SDS or dioctanoyl phosphatidylglycerol. This
      structure is retained in the C-terminal fragment LL-37(13-37) and very likely in
      intact LL-37 based on peptide-aided signal assignments. The higher antibacterial
      activity of the LL-37 core peptide than aurein 1.2 was attributed to additional
      cationic residues. To achieve selective membrane targeting, D-amino acids were
      incorporated into LL-37(17-32). While the D-peptide showed similar antibacterial
      activity to the L-diastereomer, it lost toxicity to human cells. Structural
      analysis revealed hydrophobic defects in the new amphipathic structure of the D
      peptide, leading to a much shorter retention time on a reversed-phase HPLC
      column. It is proposed that hydrophobic defects as a result of incoherent
      hydrophobic packing provide a structural basis for the improvement in cell
      selectivity of the LL-37 fragment.

PMID- 16637647
TI  - Conformational equilibrium of cytochrome P450 BM-3 complexed with N
      palmitoylglycine: a replica exchange molecular dynamics study.
AB  - UV-vis absorbance measurements and associated studies of cytochrome P450 BM-3 in
      complex with N-palmitoylglycine (NPG) indicate that a conformational change
      occurs in the active site of the complex where the terminal atoms of the ligand
      move from a site distant from the heme iron, as seen in the low temperature
      crystal structure to a site proximal to the heme iron at biological temperatures.
      We employ replica exchange molecular dynamics simulations to study this
      conformational change. The population of the proximal state is found to increase
      with temperature in agreement with UV-vis absorbance and NMR measurements. In
      addition to the conformations characterized by X-ray crystallography and computer
      modeling, this study shows that a new conformational state is significantly
      populated at room temperature. The observed increase in the population of
      conformations where the terminal atoms of NPG are proximal to the heme iron with
      increasing temperature indicates that the proximal state is stabilized by
      conformational entropy. A proposal for the origin of this entropic stabilization
      is provided on the basis of the structure of the newly identified state. We use
      the temperature weighted histogram (T-WHAM) method to characterize the transition
      state regions of the conformational ensemble and propose a mechanism of
      interconversion between these low free energy conformational states.

PMID- 16637648
TI  - Fluorocarbon-modified organic semiconductors: molecular architecture, electronic,
      and crystal structure tuning of arene- versus fluoroarene-thiophene oligomer thin
      film properties.
AB  - We present here the systematic synthesis and comparative physicochemical
      characterization of a series of regiochemically varied and core size extension
      modulated arene(perfluoroarene)-thiophene oligomers. The molecules investigated
      are: 5,5''-diphenyl-2,2':5',2'':5'',2'''-quaterthiophene (1), 5,5'-bis[1-[4
      (thien-2-yl)phenyl]]-2,2'-dithiophene (2), 4,4'-bis[5-(2,2'-dithiophenyl)]
      biphenyl (3), 5,5''-diperfluorophenyl-2,2':5',2'':5'',2'''-quaterthiophene (4),
      5,5'-bis[1-[4-(thien-2-yl)perfluorophenyl]]-2,2'-dithiophene (5), 4,4'-bis[5
      (2,2'-dithiophenyl)]-perfluorobiphenyl (6), 5,5''-diperfluorophenyl-2,2':5',2''
      tertthiophene (7), 5,5'-diperfluorophenyl-2,2'-dihiophene (8), and 5,5
      diperfluorophenylthiophene (9). Trends in optical absorption and emission
      parameters, molecular structures as defined by single-crystal X-ray diffraction,
      as well as electrochemical redox processes are described. The morphologies and
      microstructures of the vapor-deposited films grown over a range of growth
      temperatures have also been characterized. Field-effect transistor (FET)
      measurements demonstrate that all of these materials are FET-active and,
      depending on the molecular architecture, exhibit comparably good p- or n-type
      mobility when optimum film microstructural order is achieved. A very large n
      channel mobility of approximately 0.5 cm2/Vs with I(on)/I(off) ratios > 10(8) is
      achieved for films of 4.

PMID- 16637650
TI  - Detailed structure of diamond-type lipid cubic nanoparticles.
AB  - Supramolecular three-dimensional self-assembly of nonlamellar lipids with
      fragments of the protein immunoglobulin results in a bicontinuous cubic phase
      fragmented into nanoparticles with open water channels (cubosomes). The structure
      of the diamond-type cubic nanoparticles is characterized experimentally by freeze
      fracture electron microscopy, and it is mathematically modeled with nodal
      surfaces emphasizing the fluid-like undulations of the cubosomic interfaces.
      Based on scaling-up and scaling-down approaches, we present stable and
      intermediate-kind nanoparticles resulting from the cubosomic growth. Our results
      reveal the smallest stable diamond-type cubosomic entity that can serve as a
      building block of more complex nanostructured fluid drug delivery vehicles of
      therapeutic proteins. The evidence presented for lipid-bilayer undulations in the
      surface region of the protein/lipid cubosomes could have important consequences
      for possible applications of these hierarchically organized porous nanoparticles.

PMID- 16637649
TI  - The paradoxical thermodynamic basis for the interaction of ethylene glycol,
      glycine, and sarcosine chains with bovine carbonic anhydrase II: an unexpected
      manifestation of enthalpy/entropy compensation.
AB  - This paper describes a systematic study of the thermodynamics of association of
      bovine carbonic anhydrase II (BCA) and para-substituted benzenesulfonamides with
      chains of oligoglycine, oligosarcosine, and oligoethylene glycol of lengths of
      one to five residues. For all three of these series of ligands, the enthalpy of
      binding became less favorable, and the entropy less unfavorable, as the chain
      length of the ligands increased. The dependence on chain length of the enthalpy
      was almost perfectly compensated by that of the entropy; this compensation
      resulted in dissociation constants that were independent of chain length for the
      three series of ligands. Changes in heat capacity were independent of chain
      length for the three series and revealed that the amount of molecular surface
      area buried upon protein-ligand complexation did not increase with increasing
      chain length. Taken together, these data refute a model in which the chains of
      the ligands interact hydrophobically with the surface of BCA. To explain the
      data, a model is proposed based on decreasing "tightness" of the protein-ligand
      interface as the chain length of the ligand increases. This decreasing tightness,
      as the chain length increases, is reflected in a less favorable enthalpy (due to
      fewer van der Waals contacts) and a less unfavorable entropy (due to greater
      mobility of the chain) of binding for ligands with long chains than for those
      with short chains. Thus, this study demonstrates a surprising example of
      enthalpy/entropy compensation in a well-defined system. Understanding this
      compensation is integral to the rational design of high-affinity ligands for
      proteins.

PMID- 16637651
TI  - Dramatic acceleration of the pd-catalyzed [4+2] benzannulation reaction of enynes
      and diynes in the presence of lewis acids and bases: expanded scope and new
      mechanistic insights.
AB  - Dramatic acceleration of the palladium catalyzed [4+2] benzannulation and
      sequential [2+2+2] trimerization reactions in the presence of a Lewis
      acid/phosphine combination or in the presence of Bronsted bases has been
      explored. These novel sets of conditions allowed for remarkable enhancement of
      reaction rates and broadening of the substrate scope and for a significant
      improvement of reaction yields, particularly for problematic pentasubstituted
      benzenes. It was found that the real nature of Lewis acid acceleration does not
      only lie in the isomerization of conjugated enynes but also in the direct
      acceleration of the [4+2] benzannulation reaction. These experimental findings,
      combined with the deuterium-labeling studies and DFT calculations, led to a
      mechanistic rationale, which (a) reasonably accounts for the observed
      acceleration of the reaction by Lewis acid and bases; (b) provides a viable
      alternative route for the ring-closing step in the mechanism of benzannulation;
      (c) clarifies the mechanism of hydrogen migration; and (d) for the first time
      provides a rationale for the origins of the remarkable stereoselectivity of the
      hydrogen migration during the benzannulation reaction.

PMID- 16637652
TI  - Electron binding motifs of (H2O)n- clusters.
AB  - It is has been established that the excess electrons in small (i.e., n < or = 7)
      (H2O)n- clusters are bound in the dipole field of the neutral cluster and, thus,
      exist as surface states. However, the motifs for the binding of an excess
      electron to larger water clusters remain the subject of considerable debate. The
      prevailing view is that electrostatic interactions with the "free" OH bonds of
      the cluster dominate the binding of the excess electron in both small and large
      clusters. In the present study, a quantum Drude model is used to study selected
      (H2O)n- clusters in the n = 12-24 size range with the goal of elucidating
      different possible binding motifs. In addition to the known surface and cavity
      states, we identify a new binding motif, where the excess electron permeates the
      hydrogen-bonding network. It is found that electrostatic interactions dominate
      the binding of the excess electron only for isomers with large dipole moments,
      whereas in isomers without large dipole moments polarization and correlation
      effects dominate. Remarkably, for the network-permeating states, the excess
      electron binds even in the absence of electrostatic interactions.

PMID- 16637653
TI  - Intermolecular transfer of copper ions from the CopC protein of Pseudomonas
      syringae. Crystal structures of fully loaded Cu(I)Cu(II) forms.
AB  - CopC is a small soluble protein expressed in the periplasm of Pseudomonas
      syringae pathovar tomato as part of its copper resistance response (cop operon).
      Equilibrium competition reactions confirmed two separated binding sites with high
      affinities for Cu(I) (10(-7) > or = K(D) > or = 10(-13) M) and Cu(II) (K(D) = 10(
      13(1)) M), respectively. While Cu(I)-CopC was converted cleanly by O2 to Cu(II)
      CopC, the fully loaded form Cu(I)Cu(II)-CopC was stable in air. Variant forms H1F
      and H91F exhibited a lower affinity for Cu(II) than does the wild-type protein
      while variant E27G exhibited a higher affinity. Cation exchange chromatography
      detected each of the four different types of intermolecular copper transfer
      reactions possible between wild type and variant forms: Cu(I) site to Cu(II)
      site; Cu(II) site to Cu(I) site; Cu(I) site to Cu(I) site; Cu(II) site to Cu(II)
      site. The availability of an unoccupied site of higher affinity induced
      intermolecular transfer of either Cu(I) or Cu(II) in the presence of O2 while
      buffering concentrations of cupric ion at sub-picomolar levels. Crystal
      structures of two crystal forms of wild-type Cu(I)Cu(II)-CopC and of the apo-H91F
      variant demonstrate that the core structures of the molecules in the three
      crystal forms are conserved. However, the conformations of the amino terminus (a
      Cu(II) ligand) and the two copper-binding loops (at each end of the molecule)
      differ significantly, providing the structural lability needed to allow transfer
      of copper between partners, with or without change of oxidation state. CopC has
      the potential to interact directly with each of the four cop proteins coexpressed
      to the periplasm.

PMID- 16637654
TI  - Measurement of long-range 1H-19F scalar coupling constants and their glycosidic
      torsion dependence in 5-fluoropyrimidine-substituted RNA.
AB  - Long-range scalar 5J(H1',F) couplings were observed in 5-fluoropyrimidine
      substituted RNA. We developed a novel S3E-19F-alpha,beta-edited NOESY experiment
      for quantitation of these long-range scalar 5J(H1',F) couplings, where the J
      couplings can be extracted from inspection of intraresidual (H1',H6) NOE cross
      peaks. Quantum chemical calculations were exploited to investigate the relation
      between scalar couplings and conformations around the glycosidic bond in
      oligonucleotides. The theoretical dependence of the observed 5J(H1',F) couplings
      on the torsion angle chi can be described by a generalized Karplus relationship.
      The corresponding density functional theory (DFT) analysis is outlined.
      Additional NMR experiments facilitating the resonance assignments of 5
      fluoropyrimidine-substituted RNAs are described, and chemical shift changes due
      to altered shielding in the presence of fluorine-19 (19F) are presented.

PMID- 16637655
TI  - C7 and C9 carbon-rich bridges in diruthenium systems: synthesis, spectroscopic,
      and theoretical investigations of different oxidation States.
AB  - Two methodologies of C-C bond formation to achieve organometallic complexes with
      7 or 9 conjugated carbon atoms are described. A C7 annelated trans
      [Cl(dppe)2Ru=C=C=C-CH=C(CH2)-C[triple bond]C-Ru(dppe)2Cl][X] (X = PF6, OTf)
      complex is obtained from the diyne trans-[Cl(dppe)2Ru-(C[triple bond]C)2-R] (R =
      H, SiMe3) in the presence of [FeCp2][PF6] or HOTf, and C7 or C9 complexes trans
      [Cl(dppe)2Ru-(C[triple bond]C)n-C(CH3)=C(R1)-C(R2)=C=C=Ru(dppe)2Cl][X] (n = 1, 2;
      R1 = Me, Ph, R2 = H, Me; X = BF4, OTf) are formed in the presence of a polyyne
      trans-[Cl(dppe)2Ru-(C[triple bond]C)n-R] (n = 2, 3; R = H, SiMe3) with a
      ruthenium allenylidene trans-[Cl(dppe)2Ru=C=C=C(CH2R1)R2][X]. These reactions
      proceed under mild conditions and involve cumulenic intermediates [M+]=(C=)nCHR
      (n = 3, 5), including a hexapentaenylidene. A combination of chemical,
      electrochemical, spectroscopic (UV-vis, IR, NIR, EPR), and theoretical (DFT)
      techniques is used to show the influence of the nature and conformation of the
      bridge on the properties of the complexes and to give a picture of the electron
      delocalization in the reduced and oxidized states. These studies demonstrate that
      the C7 bridging ligand spanning the metal centers by almost 12 angstroms is
      implicated in both redox processes and serves as a molecular wire to convey the
      unpaired electron with no tendency for spin localization on one of the halves of
      the molecules. The reactivity of the C7 complexes toward protonation and
      deprotonation led to original bis(acetylides), vinylidene-allenylidene, or
      carbyne-vinylidene species such as trans-[Cl(dppe)2Ru[triple bond]C-CH=C(CH3)
      CH=C(CH3)-HC=C=Ru(dppe)2Cl][BF4]3.

PMID- 16637656
TI  - Nanoscale patterning of two metals on silicon surfaces using an ABC triblock
      copolymer template.
AB  - Patterning technologically important semiconductor interfaces with nanoscale
      metal films is important for applications such as metallic interconnects and
      sensing applications. Self-assembling block copolymer templates are utilized to
      pattern an aqueous metal reduction reaction, galvanic displacement, on silicon
      surfaces. Utilization of a triblock copolymer monolayer film, polystyrene-block
      poly(2-vinylpyridine)-block-poly(ethylene oxide) (PS-b-P2VP-b-PEO), with two
      blocks capable of selective transport of different metal complexes to the surface
      (PEO and P2VP), allows for chemical discrimination and nanoscale patterning.
      Different regions of the self-assembled structure discriminate between metal
      complexes at the silicon surface, at which time they undergo the spontaneous
      reaction at the interface. Gold deposition from gold(III) compounds such as
      HAuCl4(aq) in the presence of hydrofluoric acid mirrors the parent block
      copolymer core structure, whereas silver deposition from Ag(I) salts such as
      AgNO3(aq) does the opposite, localizing exclusively under the corona. By carrying
      out gold deposition first and silver second, sub-100-nm gold features surrounded
      by silver films can be produced. The chemical selectivity was extended to other
      metals, including copper, palladium, and platinum. The interfaces were
      characterized by a variety of methods, including scanning electron microscopy,
      scanning Auger microscopy, X-ray photoelectron spectroscopy, and atomic force
      microscopy.

PMID- 16637657
TI  - Design, synthesis, and conformational dynamics of a gated molecular basket.
AB  - We have developed a synthesis and examined the conformational behavior and
      recognition properties of dynamic molecular containers 1-3. As follows from the
      1H NMR dilution, diffusion NMR, and vapor pressure osmometry measurements,
      compound 1 has a low affinity for intermolecular aggregation and is mostly
      present in monomeric form in dilute chloroform solutions. Inspecting the O-H
      chemical shift resonances of 1, 3, and model compound 4 as a function of
      temperature afforded the deltadelta/deltaT coefficients of 17.0, 17.3, and 4.7
      ppb K(-1), respectively. In combination with the results from variable
      temperature 1H NMR and IR measurements, the existence of conformers of 1 and 3 in
      equilibrium, each having a different extent of hydrogen bonding, was confirmed.
      Molecular mechanics calculations suggested 1a as the most favorable conformation,
      with three additional conformers, 1b, 1c, and 1d, populating local energy minima.
      Further optimization of each of the four conformers using semiempirical PM3 and
      ab initio (HF/6-31G) methods allowed a determination of their relative free
      energies and the corresponding Boltzmann population distributions which were
      heavily weighted toward 1a. A computed composite IR spectrum of a fraction
      weighted mixture of the conformers of 1 reproduced the experimentally observed IR
      spectrum in its structural features, leading to a conclusion that conformer 1a
      indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 angstroms3)
      is complementary in size, shape, and electrostatic potential to chloroform (74.9
      angstroms3). A single-crystal X-ray study of 2 revealed a disordered chloroform
      molecule positioned inside the cavitand along its C3 axis.

PMID- 16637658
TI  - Anion-pi interactions as controlling elements in self-assembly reactions of Ag(I)
      complexes with pi-acidic aromatic rings.
AB  - Reactions of 3,6-bis(2'-pyridyl)-1,2,4,5-tetrazine (bptz) and 3,6-bis(2'-pyridyl)
      1,2-pyridazine (bppn) with the AgX salts (X = [PF6]-, [AsF6]-, [SbF6]-, and [BF4]
      ) afford complexes of different structural motifs depending on the pi-acidity of
      the ligand central ring and the outer-sphere anion. The bptz reactions lead to
      the polymeric [[Ag(bptz)][PF6]]infinity (1) and the dinuclear compounds
      [Ag2(bptz)2(CH3CN)2][PF6]2 (2) and [Ag2(bptz)2(CH3CN)2][AsF6]2 (3), as well as
      the propeller-type species [Ag2(bptz)3][AsF6]2 (4) and [Ag2(bptz)3][SbF6]2 (5a
      and 5b). Reactions of bppn with AgX produce the grid-type structures
      [Ag4(bppn)4][X]4 (6-9), regardless of the anion present. In 6-9, pi-pi stacking
      interactions are maximized, whereas multiple and shorter (therefore stronger)
      anion-pi interactions between the anions and the tetrazine rings are established
      in 1-5b. These differences reflect the more electron-rich character of the bppn
      pyridazine ring as compared to the bptz tetrazine ring. The evidence gleaned from
      the solid-state structures was corroborated by density functional theory
      calculations. In the electrostatic potential maps of the free ligands, a higher
      positive charge is present in the bptz as compared to the bppn central ring.
      Furthermore, the electrostatic potential maps of 3, 4, and 5b indicate an
      electron density transfer from the anions to the pi-acidic rings. Conversely,
      upon addition of the [AsF6]- ions to the cation of 7, there is negligible change
      in the electron density of the central pyridazine ring, which supports the
      presence of weaker anion-pi interactions in the bppn as compared to the bptz
      complexes. From the systems studied herein, it is concluded that anion-pi
      interactions play an important role in the outcome of self-assembly reactions.

PMID- 16637659
TI  - Uncovering quantitative protein interaction networks for mouse PDZ domains using
      protein microarrays.
AB  - One of the principal challenges in systems biology is to uncover the networks of
      protein-protein interactions that underlie most biological processes. To date,
      experimental efforts directed at this problem have largely produced only
      qualitative networks that are replete with false positives and false negatives.
      Here, we describe a domain-centered approach--compatible with genome-wide
      investigations--that enables us to measure the equilibrium dissociation constant
      (K(D)) of recombinant PDZ domains for fluorescently labeled peptides that
      represent physiologically relevant binding partners. Using a pilot set of 22 PDZ
      domains, 4 PDZ domain clusters, and 20 peptides, we define a gold standard
      dataset by determining the K(D) for all 520 PDZ-peptide combinations using
      fluorescence polarization. We then show that microarrays of PDZ domains identify
      interactions of moderate to high affinity (K(D) < or = 10 microM) in a high
      throughput format with a false positive rate of 14% and a false negative rate of
      14%. By combining the throughput of protein microarrays with the fidelity of
      fluorescence polarization, our domain/peptide-based strategy yields a
      quantitative network that faithfully recapitulates 85% of previously reported
      interactions and uncovers new biophysical interactions, many of which occur
      between proteins that are co-expressed. From a broader perspective, the
      selectivity data produced by this effort reveal a strong concordance between
      protein sequence and protein function, supporting a model in which interaction
      networks evolve through small steps that do not involve dramatic rewiring of the
      network.

PMID- 16637660
TI  - Chiral amphiphilic self-assembled alpha,alpha'-linked quinque-, sexi-, and
      septithiophenes: synthesis, stability and odd-even effects.
AB  - The synthesis, characterization, and self-assembly in butanol of a series of well
      defined alpha,alpha'-linked quinqui-, sexi-, and septithiophenes substituted, via
      ester links at their termini, by chiral oligo(ethylene oxide) chains carrying an
      alpha, beta, delta, and epsilon methyl, respectively, are reported. Studies of
      the self-assembly of these molecules using UV/visible absorption, luminescence,
      and circular dichroism spectroscopies reveal, for the sexithiophene case, that
      the magnitude of the observed Cotton effect in the aggregates diminishes
      progressively as the chiral substituent is moved away from the thiophene segment.
      The stability of the assemblies increases with the length of the oligothiophene
      and as the substituent chiral unit is moved away from the aromatic core, being
      greatest for the unsubstituted case. The sign of the Cotton effect alternates in
      an "odd/even" manner as the position of the chiral substituent is moved along the
      oligo(ethylene oxide) chain and on going from the quinquethiophene to the
      septithiophene having the same side chain. Atomic force microscopy on materials
      deposited from solution on an aluminum or glass surface and optical measurements
      show that capsules are formed from the oligothiophenes with H-type packing of the
      aromatic segments.

PMID- 16637661
TI  - Reaction of the acetals with TESOTf-base combination; speculation of the
      intermediates and efficient mixed acetal formation.
AB  - We report here unexpected highly chemoselective deprotection of the acetals from
      aldehydes. Treatment of acetal compounds from aldehydes with TESOTf-2,6-lutidine
      or TESOTf-2,4,6-collidine in CH2Cl2 at 0 degrees C followed by H2O workup at the
      same temperature caused the conversion of the acetal functions to aldehyde
      functions. The reaction had generality and was applied to many acetal compounds.
      Study using various bases revealed the reaction and reached the best combination
      of TESOTf-base. It was very mild and highly chemoselective and proceeded under
      weakly basic conditions. Then, many functional groups such as allyl alcohol,
      silyl ether, acetate, methyl ether, triphenylmethyl (Tr) ether, 1,3-dithiolane,
      methyl ester, and tert-butyl ester could survive under these conditions.
      Furthermore, this methodology could selectively deprotect the acetals in the
      presence of ketals as the most characteristic feature, although this
      chemoselectivity is difficult to achieve by other previously reported methods. A
      detailed study of the reaction including MS and NMR studies revealed the reaction
      mechanism for determining the structures of the intermediates, pyridinium-type
      salts. These intermediates had a weak electrophilicity and were successfully
      applied to the efficient formation of the mixed acetals in high yields.

PMID- 16637662
TI  - Lithiated imines: solvent-dependent aggregate structures and mechanisms of
      alkylation.
AB  - We describe efforts to understand the structure and reactivity of lithiated
      cyclohexanone N-cyclohexylimine. The lithioimine affords complex solvent
      dependent distributions of monomers, dimers, and trimers in a number of ethereal
      solvents. Careful selection of solvent provides exclusively monosolvated dimers.
      Rate studies on the C-alkylations reveal chronic mixtures of monomer- and dimer
      based pathways. We explore the factors influencing reactants and alkylation
      transition structures and the marked differences between lithioimines and
      isostructural lithium dialkylamides with the aid of density functional theory
      calculations.

PMID- 16637663
TI  - Physiochemical pathway for cyclic dehydrogenation and rehydrogenation of LiAlH4.
AB  - A five-step physiochemical pathway for the cyclic dehydrogenation and
      rehydrogenation of LiAlH4 from Li3AlH6, LiH, and Al was developed. The LiAlH4
      produced by this physiochemical route exhibited excellent dehydrogenation
      kinetics in the 80-100 degrees C range, providing about 4 wt % hydrogen. The
      decomposed LiAlH4 was also fully rehydrogenated through the physiochemical
      pathway using tetrahydrofuran (THF). The enthalpy change associated with the
      formation of a LiAlH4.4THF adduct in THF played the essential role in fostering
      this rehydrogenation from the Li3AlH6, LiH, and Al dehydrogenation products. The
      kinetics of rehydrogenation was also significantly improved by adding Ti as a
      catalyst and by mechanochemical treatment, with the decomposition products
      readily converting into LiAlH4 at ambient temperature and pressures of 4.5-97.5
      bar.

PMID- 16637664
TI  - A new class of versatile chiral-bridged atropisomeric diphosphine ligands:
      remarkably efficient ligand syntheses and their applications in highly
      enantioselective hydrogenation reactions.
AB  - A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by
      atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann
      coupling reaction of the biaryl diphosphine dioxides is featured by highly
      efficient central-to-axial chirality transfer with diastereomeric excess >99%.
      This substrate-directed diastereomeric biaryl coupling reaction is unprecedented
      for the preparation of chiral diphosphine dioxides, and our method precludes the
      tedious resolution procedures usually required for preparing enantiomerically
      pure diphosphine ligands. The effect of chiral recognition was also revealed in a
      relevant asymmetric ring-closure reaction. The chiral tether bridging the two
      aryl units creates a conformationally rigid scaffold essential for enantiofacial
      differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can
      be achieved by varying the chain length of the chiral tether. The
      enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied
      to the catalytic enantioselective hydrogenations of alpha- and beta-ketoesters
      (C=O bond reduction), 2-(6'-methoxy-2'-naphthyl)propenoic acid, alkyl-substituted
      beta-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N
      bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been
      attained for the catalytic reactions. In addition, the significant ligand
      dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N
      heteroaromatic compounds were also revealed.

PMID- 16637665
TI  - Engineering the quadruplex fold: nucleoside conformation determines both folding
      topology and molecularity in guanine quadruplexes.
AB  - Nucleic acid quadruplexes, based on the guanine quartet, can arise from one or
      several strands, depending on the sequence. Those consisting of a single strand
      are usually folded in one of two principal topologies: antiparallel, in which all
      or half of the guanine stretches are antiparallel to each other, or parallel, in
      which all guanine stretches are parallel to each other. In the latter, all
      guanine nucleosides possess the anti conformation about the glycosidic bond,
      while in the former, half possess the anti conformation, and half possess the syn
      conformation. While antiparallel is the more common fold, examples of
      biologically important, parallel quadruplexes are becoming increasingly common.
      Thus, it is of interest to understand the forces that determine the quadruplex
      fold. Here, we examine the influence of individual nucleoside conformation on the
      overall folding topology by selective substitution of rG for dG. We can reverse
      the antiparallel fold of the thrombin binding aptamer (TBA) by this approach.
      Additionally, this substitution converts a unimolecular quadruplex into a
      bimolecular one. Similar reverse substitutions in the all-RNA analogue of TBA
      result in a parallel to antiparallel change in topology and alter the strand
      configuration from bimolecular to unimolecular. On the basis of the specific
      substitutions made, we conclude that the strong preference of guanine
      ribonucleosides for the anti conformation is the driving force for the change in
      topology. These results demonstrate how conformational properties of guanine
      nucleosides govern not only the quadruplex folding topology but also impact
      quadruplex molecularity and provide a means to control these properties.

PMID- 16637666
TI  - Methane activation by titanium monoxide molecules: a matrix isolation infrared
      spectroscopic and theoretical study.
AB  - Reactions of titanium monoxides with methane have been investigated using matrix
      isolation infrared spectroscopy and theoretical calculations. Titanium
      derivatives of several simple oxyhydrocarbons have been prepared and identified.
      The titanium monoxide molecules prepared by laser evaporation of bulk TiO2 target
      reacted with methane to form the TiO(CH4) complex in solid argon, which was
      predicted to have C3v symmetry with the oxygen atom coordinated to one hydrogen
      atom of the methane molecule. The complex rearranged to the CH3Ti(O)H titano
      acetaldehyde molecule upon visible (lambda > 500 nm) irradiation. The titano
      acetaldehyde molecule sustained further photochemical rearrangement to the
      CH2Ti(H)OH titano-vinyl alcohol molecule, which was characterized to be a simple
      carbene complex involving agostic bonding. The CH2Ti(H)OH molecule reacted with a
      second methane to form the (CH3)2Ti(H)OH titano-isopropyl alcohol molecule
      spontaneously on annealing. The (CH3)2Ti(H)OH molecule also can be produced via
      UV photon-induced rearrangement of the CH3Ti(O)H(CH4) complex.

PMID- 16637668
TI  - Need for an "integrated safety assessment" of GMOs, linking food safety and
      environmental considerations.
AB  - Evidence for substantial environmental influences on health and food safety comes
      from work with environmental health indicators which show that agroenvironmental
      practices have direct and indirect effects on human health, concluding that "the
      quality of the environment influences the quality and safety of foods" [Fennema,
      O. Environ. Health Perspect. 1990, 86, 229-232). In the field of genetically
      modified organisms (GMOs), Codex principles have been established for the
      assessment of GM food safety and the Cartagena Protocol on Biosafety outlines
      international principles for an environmental assessment of living modified
      organisms. Both concepts also contain starting points for an assessment of
      health/food safety effects of GMOs in cases when the environment is involved in
      the chain of events that could lead to hazards. The environment can act as a
      route of unintentional entry of GMOs into the food supply, such as in the case of
      gene flow via pollen or seeds from GM crops, but the environment can also be
      involved in changes of GMO-induced agricultural practices with relevance for
      health/food safety. Examples for this include potential regional changes of
      pesticide uses and reduction in pesticide poisonings resulting from the use of Bt
      crops or influences on immune responses via cross-reactivity. Clearly, modern
      methods of biotechnology in breeding are involved in the reasons behind the rapid
      reduction of local varieties in agrodiversity, which constitute an identified
      hazard for food safety and food security. The health/food safety assessment of GM
      foods in cases when the environment is involved needs to be informed by data from
      environmental assessment. Such data might be especially important for hazard
      identification and exposure assessment. International organizations working in
      these areas will very likely be needed to initiate and enable cooperation between
      those institutions responsible for the different assessments, as well as for
      exchange and analysis of information. An integrated assessment might help to
      focus and save capacities in highly technical areas such as molecular
      characterization or profiling, which are often necessary for both assessments. In
      the area of establishing international standards for traded foods, such as for
      the newly created Standards in Trade and Development Facility (STDF), an
      integrated assessment might help in the consideration of important environmental
      aspects involved in health and food safety. Furthermore, an established
      integrated view on GMOs may create greater consumer confidence in the technology.

PMID- 16637669
TI  - Enzymatic assay method for evaluating the lipase activity in complex extracts
      from transgenic corn seed.
AB  - A colorimetric method was established to determine the activity of recombinant
      lipase in extracts from transgenic corn seed. The system was an oil-in-water
      emulsion that was stabilized by a surfactant to accommodate the organic phase
      substrate and aqueous phase enzyme. The lipase activity was measured by
      monitoring the release of nitrophenol at 346 nm from the substrate, 4-nitrophenyl
      butyrate. Emulsions prepared with various surfactant types and concentrations
      were tested. For each surfactant, the measured activity was greatest when the
      surfactant concentration was close to the critical micelle concentration,
      consistent with the changing trend of oil droplet size as a function of
      surfactant concentration. The optimal system, with 0.01% (w/w) Tween 80,
      demonstrated good reproducibility, high sensitivity, robustness, and a linear
      response to lipase concentration.

PMID- 16637670
TI  - Quantification of fatty acids in forages by near-infrared reflectance
      spectroscopy.
AB  - Near-infrared reflectance spectroscopy (NIRS) was evaluated as a possible
      alternative to gas chromatography (GC) for the quantitative analysis of fatty
      acids in forages. Herbage samples from 11 greenhouse-grown forage species
      (grasses, legumes, and forbs) were collected at three stages of growth. Samples
      were freeze-dried, ground, and analyzed by GC and NIRS techniques. Half of the
      195 samples were used to develop an NIRS calibration file for each of eight fatty
      acids, with the remaining half used as a validation data set. Spectral data,
      collected over a wavelength range of 1100-2498 nm, were regressed against GC data
      to develop calibration equations for lauric (C12:0), myristic (C14:0), palmitic
      (C16:0), stearic (C18:0), palmitoleic (C16:1), oleic (C18:1), linoleic (C18:2),
      and alpha-linolenic (C18:3) acids. Calibration equations had high coefficients of
      determination for calibration (0.93-0.99) and cross-validation (0.89-0.98), and
      standard errors of calibration and cross-validation were < 20% of the respective
      means. Simple linear regressions of NIRS results against GC data for the
      validation data set had r2 values ranging from 0.86 to 0.97. Regression slopes
      for C12:0, C14:0, C16:0, C18:0, C16:1, C18:2, and C18:3 were not significantly
      different (P = 0.05) from 1.0. The regression slope for C18:1 was 1.1. The ratio
      of standard error of prediction to standard deviation was > 3.0 for all fatty
      acids except C12:0 (2.6) and C14:0 (2.9). Validation statistics indicate that
      NIRS has high prediction ability for fatty acids in forages. Calibration
      equations developed using data for all plant materials accurately predicted
      concentrations of C16:0, C18:2, and C18:3 in individual plant species. Accuracy
      of prediction was less, but acceptable, for fatty acids (C12:0, C14:0, C18:0,
      C16:1, and C18:1) that were less prevalent.

PMID- 16637671
TI  - Determination of 17alpha-methyltestosterone in muscle tissues of tilapia, rainbow
      trout, and salmon using liquid chromatography-tandem mass spectrometry.
AB  - An analytical method was developed to quantitate and confirm the presence of
      17alpha-methyltestosterone in the muscles of tilapia, rainbow trout, and salmon.
      The method employed two liquid-liquid partitioning steps and two solid-phase
      extraction columns for sample cleanup. The final extracts were analyzed on an
      isocratic reverse-phase liquid chromatography-tandem mass spectrometry system
      with atmospheric-pressure chemical ionization in the positive ion mode. The
      method was validated at levels from 0.40 to 1.6 ng/g, with MT-d3 used as an
      internal standard. The accuracy was between 100% and 110%, and coefficients of
      variation of <10% were obtained for all three fish species. Muscle tissues from
      dosed fish were also assayed to demonstrate the effectiveness of the method for
      recovering the parent drug.

PMID- 16637672
TI  - Development of a gas-liquid chromatographic method for the analysis of fatty acid
      tryptamides in cocoa products.
AB  - The determination of the occurrence and level of cocoa shells in cocoa products
      and chocolate is an important analytical issue. The recent European Union
      directive on cocoa and chocolate products (2000/36/EC) has not retained the
      former limit of a maximum amount of 5% of cocoa shells in cocoa nibs (based on
      fat-free dry matter), previously authorized for the elaboration of cocoa products
      such as cocoa mass. In the present study, we report a reliable gas-liquid
      chromatography procedure suitable for the determination of the occurrence of
      cocoa shells in cocoa products by detection of fatty acid tryptamides (FATs). The
      precision of the method was evaluated by analyzing nine different samples (cocoa
      liquors with different ranges of shells) six times (replicate repeatability). The
      variations of the robust coefficient of variation of the repeatability
      demonstrated that FAT(C22), FAT(C24), and total FATs are good markers for the
      detection of shells in cocoa products. The trueness of the method was evaluated
      by determining the FAT content in two spiked matrices (cocoa liquors and cocoa
      shells) at different levels (from 1 to 50 mg/100 g). A good relation was found
      between the results obtained and the spiking (recovery varied between 90 and
      130%), and the linearity range was established between 1 and 50 mg/100 g in cocoa
      products. For total FAT contents of cocoa liquor containing 5% shells, the
      measurement uncertainty allows us to conclude that FAT is equal to 4.01 +/- 0.8
      mg/100 g. This validated method is perfectly suitable to determine shell contents
      in cocoa products using FAT(C22), FAT(C24), and total FATs as markers. The
      results also confirmed that cocoa shells contain FAT(C24) and FAT(C22) in a
      constant ratio of nearly 2:1.

PMID- 16637673
TI  - A simple high-performance liquid chromatography method for the determination of
      throat-burning oleocanthal with probated antiinflammatory activity in extra
      virgin olive oils.
AB  - A high-performance liquid chromatography (HPLC) method was developed to
      quantitatively analyze oleocanthal in extra virgin olive oils. Oleocanthal, a
      deacetoxy ligstroside aglycone, is known to be responsible for the back of the
      throat irritation of olive oils and to have probated antiinflamatory activity.
      Oleocanthal was isolated from small amounts of olive oil sample (1 g) by liquid
      liquid extraction. Hexane-acetonitrile was found to be the best solvent system to
      extract oleocanthal from the oil matrix. The solvent extract was analyzed by
      reversed-phase HPLC with UV detection at 278 nm. Chromatogaphic separation of
      oleocanthal from other extracted compounds and of the two geometric isomers of
      oleocanthal was achieved by an elution gradient with acetonitrile and water. Both
      the external standard calibration curve and the internal standard calibration
      curve were established, and quantitation using both calibration curves gave
      essentially the same result. The reproducibility (RSD = 4.7%), recovery (> 95%),
      and limit of quantitation (< 1 microg/g) were also determined. Concentrations of
      oleacanthal in 10 selected throat-burning extra virgin olive oils were determined
      using the method (ranged from 22 to 190 microg/g) with external standard
      calibration.

PMID- 16637674
TI  - Application of ethyl esters and d3-methyl esters as internal standards for the
      gas chromatographic quantification of transesterified fatty acid methyl esters in
      food.
AB  - Ethyl esters (FAEE) and trideuterium-labeled methyl esters (d3-FAME) of fatty
      acids were prepared and investigated regarding their suitability as internal
      standards (IS) for the determination of fatty acids as methyl esters (FAME). On
      CP-Sil 88, ethyl esters of odd-numbered fatty acids eluted approximately 0.5 min
      after the respective FAME, and only coelutions with minor FAME were observed.
      Depending on the problem, one or even many FAEE can be added as IS for the
      quantification of FAME by both GC-FID and GC-MS. By contrast, d3-FAME coeluted
      with FAME on the polar GC column, and the use of the former as IS requires
      application of GC-MS. In the SIM mode, m/z 77 and 90 are suggested for d3-methyl
      esters of saturated fatty acids, whereas m/z 88 and 101 are recommended for ethyl
      esters of saturated fatty acids. These m/z values give either no or very low
      response for FAME and can thus be used for the analysis of FAME in food by GC-MS
      in the SIM mode. Fatty acids in sunflower oil and mozzarella cheese were
      quantified using five saturated FAEE as IS. Gravimetric studies showed that the
      transesterification procedure could be carried out without of loss of fatty
      acids. GC-EI/MS full scan analysis was suitable for the quantitative
      determination of all unsaturated fatty acids in both food samples, whereas GC
      EI/MS in the SIM mode was particularly valuable for quantifying minor fatty
      acids. The novel GC-EI/MS/SIM method using fatty acid ethyl esters as internal
      standards can be used to quantify individual fatty acids only, that is, without
      determination of all fatty acids (the common 100% method), although this is
      present. This was demonstrated by the exclusive quantification of selected fatty
      acids including methyl-branched fatty acids, erucic acid (18:1n-9trans), and
      polyunsaturated fatty acids in cod liver oil and goat's milk fat.

PMID- 16637675
TI  - Fourier transform infrared spectroscopic analysis of the polymethoxylated flavone
      content of orange oil residues.
AB  - Preliminary studies have shown that orange peel polymethoxylated flavones (PMFs)
      exhibit beneficial biological properties in animals. These properties have
      increased the demands for these compounds as candidate nutraceuticals and
      specialty food ingredients. Orange oil residues are a likely commercial source of
      the PMFs, and a rapid, solvent-free method for the analysis of the PMFs in orange
      oil residues has been developed based on Fourier transform infrared (FTIR)
      spectroscopy. The intensities of the FTIR vibrations of the phenyl ring nu(C=C)
      stretch at 1515 cm(-1) of the PMFs can be used, relative to the intensity of the
      carbonyl stretch at 1733 cm(-1) of the non-PMF orange oil residue components, to
      measure PMF content. Excellent correlations for the ratios of the intensities of
      these vibrations and the total PMF content were observed irrespective of the
      source, viscosity, and presence of particulate material. The detection limit by
      this method is approximately 0.1% PMF.

PMID- 16637676
TI  - Determination of the predominant catechins in Acacia catechu by liquid
      chromatography/electrospray ionization-mass spectrometry.
AB  - A high-performance liquid chromatography coupled with electrospray ionization
      mass spectrometry (LC/ESI-MS) method under selected ion monitoring mode (SIM) was
      developed to quantitate the predominant catechins, catechin, epicatechin,
      epicatechin-3-O-gallate, and epigallocatechin-3-O-gallate, in the medicinal plant
      catechu (Acacia catechu). Other major secondary products including caffeine,
      flavanol dimers, and flavonol glycosides were also identified by their molecular
      ion peaks and fragmentation peaks using LC/MS and LC/MS/MS. For the investigated
      ion concentration ranges of catechin, epicatechin, epicatechin-3-O-gallate, and
      epigallocatechin-3-O-gallate, good linearities (r2 > 0.99) were obtained for each
      calibration curve. Validation for this method showed an accuracy ranging from
      1.06 to 11.76%, and the precision (relative standard deviation) varied between
      1.60 and 9.36% for these four analytes. This is the first quantitative
      determination of all predominant catechins in catechu heartwood and leaves.

PMID- 16637677
TI  - Time-resolved luminescence screening of antibiotics in tissue matrices without
      centrifugation and filtration: spiked recovery studies.
AB  - Analyses of chemical residues in animal tissue matrices require multistep sample
      preparation. To simplify this process, a methodology was developed that combines
      sorbent extraction and solid-matrix time-resolved luminescence (TRL); it was
      applied to tetracycline screening in milk. Reported here is an effort to extend
      its application to tissue matrices, illustrated by oxytetracycline (OTC)
      screening in catfish muscle. Extraction and enrichment are accomplished by
      immersing small C18 sorbent strips into tissue homogenates for 20 min, followed
      by a 3 min rinse in water and a 2 min dip in a reagent solution. After
      desiccation, TRL is measured directly on the sorbent surface. Tissue particulates
      no longer interfere via attenuation or scattering, rendering centrifugation and
      filtration unnecessary. The integrated TRL intensity shows a linear dependence on
      OTC concentration in the 0-8 microg/g range (R2 = 0.9992) with a 0.026 microg/g
      limit of detection. To screen OTC at 2 microg/g, the U.S. regulatory tolerance
      level, a threshold is established at x2-3sigma2, where x2 and sigma2 are the mean
      and standard deviation, respectively, of the TRL signals from 15 samples
      fortified at 2 microg/g. Among 45 blind samples randomly fortified at 0-4
      microg/g, 41 were screened correctly and 4 negative samples were presumed
      positive. This method has the potential to improve throughput and save assay
      costs by eliminating acids, organic solvents, centrifugation, and filtration.

PMID- 16637678
TI  - Pressurized liquid extraction of capsaicinoids from peppers.
AB  - A method has been developed for the extraction of capsaicinoids from peppers by
      pressurized liquid extraction (PLE); these compounds are determined by reverse
      phase high-performance liquid chromatography (HPLC), with detection by
      fluorescence spectrophotometry and mass spectrometry (MS). The stability of
      capsaicin and dihydrocapsaicin has been studied at different temperatures (50-200
      degrees C), and several extraction variables have been assayed: solvent
      (methanol, ethanol, and water), different percentages of water in the methanol (0
      20%) and in the ethanol (0-20%), and the number of extraction cycles. The study
      has evaluated the repeatability (RSD < 7%) and the reproducibility (RSD < 7%) of
      the method. Finally, the PLE method developed has been applied to quantify the
      capsaicinoids present in three varieties of hot peppers cultivated in Spain,
      quantifying five capsaicinoids: nordihydrocapsaicin, capsaicin, dihydrocapsaicin,
      an isomer of dihydrocapsaicin, and homodihydrocapsaicin.

PMID- 16637679
TI  - Comparison of solid-phase microextraction and stir bar sorptive extraction for
      the quantification of malodors in wastewater.
AB  - Malodors in wastewater from animal-rearing facilities are due to the presence of
      characteristic polar compounds. The efficiency and reproducibility of three solid
      phase microextraction (SPME) fibers (Carboxen-PDMS, polyacrylate, and PDMS) as
      well as PDMS-coated stir bars for the measurement of some of these compounds in
      the liquid phase were compared. In initial experiments, the SPME fibers and stir
      bars were exposed to a standard water solution containing a mixture of 18
      compounds with a range of octanol-water partition coefficients. The polyacrylate
      SPME fibers and PDMS-coated stir bars, having been found to possess the best
      combination of extraction efficiency and reproducibility of measurement, were
      compared for the extraction of a high-strength swine wastewater. Ten compounds,
      which are known contributors to malodors in wastewater, were quantified by both
      methods of extraction. For most compounds, greater levels were estimated by the
      PDMS-coated stir bars than by SPME, and measurement reproducibility was also
      greater. For both methods of extraction, there was greater variation in the
      measurement of volatile fatty acids than there was for aromatics.

PMID- 16637680
TI  - Evaluation of the botanical authenticity and phytochemical profile of black
      cohosh products by high-performance liquid chromatography with selected ion
      monitoring liquid chromatography-mass spectrometry.
AB  - Black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa L.) has become
      increasingly popular as a dietary supplement in the United States for the
      treatment of symptoms related to menopause, but the botanical authenticity of
      most products containing black cohosh has not been evaluated, nor is
      manufacturing highly regulated in the United States. In this study, 11 black
      cohosh products were analyzed for triterpene glycosides, phenolic constituents,
      and formononetin by high-performance liquid chromatography-photodiode array
      detection and a new selected ion monitoring liquid chromatography-mass
      spectrometry method. Three of the 11 products were found to contain the marker
      compound cimifugin and not cimiracemoside C, thereby indicating that these plants
      contain Asian Actaea instead of black cohosh. One product contained both black
      cohosh and an Asian Actaea species. For the products containing only black
      cohosh, there was significant product-to-product variability in the amounts of
      the selected triterpene glycosides and phenolic constituents, and as expected, no
      formononetin was detected.

PMID- 16637681
TI  - Lipolytic effects of citrus peel oils and their components.
AB  - This study was conducted to determine the lipolytic effects of eight kinds of
      citrus peel oils and their components. All of the citrus peel oils revealed
      lipolytic effects on olive oil model solution ranging from 10.9 to 73.8%. Hakyul
      (Citrus natsudaidai Hayata) showed the highest lipolytic effect (73.8%), followed
      by yuza (Citrus junos Sieb. ex Tanaka, 68.1%) and lemon (Citrus limonium, 63.4%),
      and their effects were comparable with or stronger than that of 5 mM raspberry
      ketone (p < 0.05). Among 17 authentic compounds relating to citrus peel oils,
      octanal (78.6%) showed the highest lipolytic effect, followed by gamma-terpinene
      (76.3%), limonene (75%), terpinen-4-ol (70.7%), nerol (69.9%), p-cymene (67.7%),
      and geranyl acetate (67.2%), and their effects were stronger than that of 5 mM
      raspberry ketone (p < 0.05). Ethyl acetate, alpha-pinene, myrcene, citronellal,
      linallyl acetate, and citronellol exhibited poor lipolytic effect in the model
      solution. Lipolytic effect was found to be high when the oils included a higher
      content of gamma-terpinene and p-cymene. Limonene showed potential lipolytic
      effect, and its effect is likely to be enhanced by the presence of gamma
      terpinene and p-cymene. It is considered that monoterpene hydrocarbons consisting
      of one or two double bonds would have stronger lipolytic effect than those having
      three double bonds.

PMID- 16637682
TI  - Minor components of olive oil modulate proatherogenic adhesion molecules involved
      in endothelial activation.
AB  - The Mediterranean diet reduces the risk of coronary artery disease as a
      consequence of its high content of antioxidants, namely, hydroxytyrosol (HT) and
      oleuropein aglycone (OleA), typical of virgin olive oil. Because intercellular
      and vascular cell adhesion molecules (ICAM-1 and VCAM-1) and E-selectin are
      crucial for endothelial activation, the role of the phenolic extract from extra
      virgin olive oil (OPE), OleA, HT, and homovanillyl alcohol (HVA) on cell surface
      and mRNA expression in human umbilical vascular endothelial cells (HUVEC) was
      evaluated. OPE strongly reduced cell surface expression of ICAM-1 and VCAM-1 at
      concentrations physiologically relevant (IC50 < 1 microM), linked to a reduction
      in mRNA levels. OleA and HT were the main components responsible for these
      effects. HVA inhibited cell surface expression of all the adhesion molecules,
      whereas the effect on mRNA expression was weaker. These results supply new
      insights on the protective role of olive oil against vascular risk through the
      down-regulation of adhesion molecules involved in early atherogenesis.

PMID- 16637683
TI  - Isolation of 6-methoxy gossypol and 6,6'-dimethoxy gossypol from Gossypium
      barbadense Sea Island cotton.
AB  - 6-methoxy gossypol and 6,6'-dimethoxy gossypol were isolated from the seeds and
      root bark of a St. Vincent Sea Island variety of cotton (AZK-267, GRIN# PI
      528406). Crude mixtures of gossypol and the methoxy compounds were obtained by
      extraction of the tissue with acetone and precipitation with acetic acid. After
      recrystallization, the preparations were treated with 3-amino-1-propanol to form
      gossypol Schiff's bases, which were separated by preparative reverse phase
      chromatography. The separated Schiff's bases were then hydrolyzed with acid,
      extracted into diethyl ether, concentrated, and precipitated with acetic acid.
      From the above procedure, both methoxy gossypol compounds were obtained as 1:1
      molar acetic acid solvates. Each compound was prepared in sufficient amounts to
      determine its physical properties and begin testing for bioactivity. Light
      absorbance differed significantly for the di-3-amino-1-propanol derivatives of
      gossypol and the methoxy gossypol compounds at 254 nm. Relative response factors
      were developed, which can be used for determining or correcting analytical
      measurements of these methylated gossypol forms.

PMID- 16637684
TI  - Quillaja saponin can modulate ovalbumin-induced IgE allergic responses through
      regulation of Th1/Th2 balance in a murine model.
AB  - Quillaja saponin is the extract from the balk of a South American tree, and it is
      considered to modulate immunological responses. We hypothesized that Quillaja
      saponin may change allergy-associated cytokine profile and antigen-specific
      immune responses. The purpose of this study is to investigate whether Quillaja
      saponin can suppress ovalbumin (OVA)-induced IgE-mediated allergic responses
      through promoting a dominant Th1 immune response. The spleen cells from BALB/c
      mice, which were primed by OVA, were used for an in vitro challenge test. The
      level of total and OVA-specific IgE, IL-4, IFN-gamma, and IL-12 was determined by
      enzyme-linked immunosorbent assay (ELISA). BALB/c mice were orally administered
      with saponin for 35 days. The mice were immunized intraperitoneally with OVA on
      days 14 and 21. After intraperitoneal challenge with OVA on day 35, anaphylactic
      symptoms were monitored. Total and specific IgE and IgG, specific IgG1 and IgG2a,
      and histamine levels in serum were analyzed by ELISA. The increase of IL-12 and
      IFN-gamma levels was observed in the presence of Quillaja saponin, while the IL-4
      level was decreased. Furthermore, Quillaja saponin suppressed total and OVA
      specific IgE secretion in spleen cells. Balb/c mice that were orally administered
      Quillaja saponin exhibited lower total and OVA-specific IgE and OVA-specific IgG
      secretions, whereas total IgG levels remained unchanged. Suppression of OVA
      specific IgG1 and an increase of OVA-IgG2a were observed in mice fed saponin.
      Quillaja saponin also decreased serum histamine levels and diminished
      anaphylactic symptoms. The present study indicates that Quillajasaponin can
      suppress allergen-specific IgE-mediated reactivity in a murine model of food
      allergy, which results from shifting from a Th2-dominated to a Th1-dominated
      immune response.

PMID- 16637685
TI  - Synthetic porcine lactoferricin with a 20-residue peptide exhibits antimicrobial
      activity against Escherichia coli, Staphylococcus aureus, and Candida albicans.
AB  - Lactoferricins are positively charged, highly basic peptides that are generated
      upon gastric pepsin cleavage of various lactoferrins. In the past decade, there
      has been active investigation of the key antimicrobial segments of the various
      shorter synthetic bovine and human lactoferricins, but not in porcine
      lactoferricin. These studies have demonstrated the distinct solution structures
      of lactoferricin in bovine and human and established the multifunctional nature
      of the antibacterial, antifungal, antiendotoxin, and antiviral activities of
      lactoferricins. However, the protective effects of porcine lactoferricins have
      yet to be elucidated. In the present study, a series of synthetic derivatives of
      porcine, bovine, and human lactoferricins with 20-residue and 9-residue peptides
      were prepared to investigate their antimicrobial nature. We found that the 20
      residue porcine lactoferricin (LFcin P-20) displayed antimicrobial activity
      against Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, and Candida
      albicans ATCC14053. The minimal inhibitory concentrations and minimal
      bactericidal concentrations of LFcin P-20 ranged from 12 to 25 microM when tested
      in bacteria and fungi. LFcin P-20 was 4 times more effective than human
      lactoferricin (LFcin H-20), but slightly less effective than bovine lactoferricin
      (LFcin B-20).

PMID- 16637686
TI  - Antioxidant properties of pearled barley fractions.
AB  - Two barley varieties (Falcon and AC Metcalfe) were separated by pearling into
      seven fractions and subsequently extracted with 80% methanol. The extracts, after
      solvent removal, were evaluated for their radical scavenging efficacy using
      Trolox equivalent antioxidant capacity (TEAC). The radical scavenging capacity of
      the extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical,
      oxygen radical absorbance capacity (ORAC(FL)), and superoxide radical assays and
      a photoinduced chemiluminescence technique. In both barley varieties the
      outermost fraction (F1) yielded the highest phenolic content. In general, Falcon
      had a significantly higher total phenolic content than AC Metcalfe. A similar
      trend was observed for TEAC, DPPH, and superoxide radical scavenging capacities
      of the extracts. The contents of water-soluble antioxidants of Falcon and AC
      Metcalfe were 1.15-12.98 and 2.20-12.25 micromol of Trolox equiv/(g of defatted
      material), while the corresponding lipid-soluble counterparts varied from 1.44 to
      4.70 micromol of alpha-tocopherol equiv/(g of defatted material). Phenolic acids,
      namely, vanillic, caffeic, p-coumaric, ferulic, and sinapic acids, were
      identified by HPLC in barley fractions.

PMID- 16637687
TI  - Physicochemical, antimicrobial, and cytotoxic characteristics of a chitosan film
      cross-linked by a naturally occurring cross-linking agent, aglycone geniposidic
      acid.
AB  - The purpose of this study was to evaluate the characteristics of a chitosan film
      cross-linked by a naturally occurring compound, aglycone geniposidic acid (aGSA).
      This newly developed aGSA-cross-linked chitosan film may be used as an edible
      film. The chitosan film without cross-linking (fresh) and the glutaraldehyde
      cross-linked chitosan film were used as controls. The characteristics of test
      chitosan films evaluated were their degree of cross-linking, swelling ratio,
      mechanical properties, water vapor permeability, antimicrobial capability,
      cytotoxicity, and enzymatic degradability. It was found that cross-linking of
      chitosan films by aGSA (at a concentration up to 0.8 mM) significantly increased
      its ultimate tensile strength but reduced its strain at fracture and swelling
      ratio. There was no significant difference in the antimicrobial capability
      between the cross-linked chitosan films and their fresh counterpart. However, the
      aGSA-cross-linked chitosan film had a lower cytotoxicity, a slower degradation
      rate, and a relatively lower water vapor permeability as compared to the
      glutaraldehyde-cross-linked film. These results suggested that the aGSA-cross
      linked chitosan film may be a promising material as an edible film.

PMID- 16637688
TI  - Permeability of starch gel matrices and select films to solvent vapors.
AB  - Volatile agrochemicals such as 2-heptanone have potential in safely and
      effectively controlling important agricultural pests provided that they are
      properly delivered. The present study reports the permeability of starch gel
      matrices and various coatings, some of which are agricultural-based, that could
      be used in controlled release devices. Low-density, microcellular starch foam was
      made from wheat, Dent corn, and high amylose corn starches. The foam density
      ranged from 0.14 to 0.34 g/cm3, the pore volume ranged from 74 to 89%, and the
      loading capacity ranged from 2.3 to 7.2 times the foam weight. The compressive
      properties of the foam were not markedly affected by saturating the pore volume
      with silicone oil. The vapor transmission rate (VTR) and vapor permeability (VP)
      were measured in dry, porous starch foam and silicone-saturated starch gels. VTR
      values were highest in foam samples containing solvents with high vapor
      pressures. Silicone oil-saturated gels had lower VTR and VP values as compared to
      the dry foam. However, the silicone oil gel did not markedly reduce the VP for 2
      heptanone and an additional vapor barrier or coating was needed to adequately
      reduce the evaporation rate. The VP of films of beeswax, paraffin, ethylene vinyl
      alcohol, a fruit film, and a laminate comprised of beeswax and fruit film was
      measured. The fruit film had a relatively high VP for polar solvents and a very
      low VP for nonpolar solvents. The laminate film provided a low VP for polar and
      nonpolar solvents. Perforating the fruit film portion of the laminate provided a
      method of attaining the target flux rate of 2-heptanone. The results demonstrate
      that the vapor flux rate of biologically active solvents can be controlled using
      agricultural materials.

PMID- 16637689
TI  - Isolation and characterization of neutral lipids of desilked eri silkworm pupae
      grown on castor and tapioca leaves.
AB  - The neutral lipid of desilked eri silkworm pupae (Samia cynthia ricini) grown on
      two different host plants, castor (Ricinus communis Linn.) and tapioca (Manihot
      utilizsima Phol.) leaves, was extracted with hexane. The oil content in pupae was
      estimated to be in the range of 18-20% (dry basis). The pupal oil was found to be
      enriched with alpha-linolenic acid (ALA) with palmitic acid as the second major
      fatty acid. The level of ALA in the oil of silkworm pupae was found to be
      significantly higher (P < 0.001) when grown on tapioca (58.3%) as compared to
      those grown on castor (42.9%). Other chemical parameters such as percent free
      fatty acid, peroxide value, phosphorus content, percent unsaponifiable matter,
      and composition of sterols were also determined in both of the oils and compared.
      Reversed-phase high-performance liquid chromatography analysis of triacylglycerol
      molecular species showed that the pupal oil is rich in molecular species with
      equivalent carbon numbers (ECN) C36, C40, C42, C44, and C48. There was a
      significantly higher level (P < 0.001) of trilinolenin (C36) in the oil of
      tapioca-based silkworm as compared to castor-based silkworm pupae. Regiospecific
      analysis of the oil showed a higher level of ALA at the sn-2 position of silkworm
      pupae grown on tapioca (60.2%) as compared to those grown on castor (47.3%) oil.
      Thus, the presence of a large amount of ALA and their predominance at the sn-2
      position make the eri pupal oil highly nutritious, provided that the oxidative
      stability is ensured.

PMID- 16637690
TI  - Comparative evaluation of the emulsifying properties of phosphatidylcholine after
      enzymatic acyl modification.
AB  - The ability of enzymatically synthesized structured phosphatidylcholine (PC)
      containing caprylic acid to form and stabilize oil-in-water emulsions prepared
      with different triglycerides [medium chain triglycerides (MCT), soybean oil, and
      enzymatically synthesized structured lipids] was examined and compared with
      natural soybean PC and deoiled lecithin. Emulsions were prepared with varying oil
      and emulsifier concentrations. The particle size distribution, creaming
      stability, and viscosity were measured for the evaluation of the emulsifying
      properties. With an increase in the oil concentration, there was an increase in
      particle size, viscosity, and creaming layer. With an increase in the
      phospholipid (PL) concentration, there was usually a decrease in particle size
      and an increase in viscosity, where the emulsion stability was increased. General
      emulsions prepared with structured lipids resulted in smaller particle sizes as
      compared to MCT and soybean oil. Deoiled lecithin was able to increase the
      viscosity more significantly and give smaller particle sizes as compared to the
      other emulsifiers, thus producing more stable emulsions. However, in certain
      cases, structured PC was superior to deoiled lecithin and soybean PC. This
      observation was made for emulsions prepared with soybean oil or structured lipid
      at an oil/water ratio of 10:90. At an oil/water ratio of 30:70, the deoiled
      lecithin performed better as compared to the other PLs with all oil types.
      However, structured PC produced more stable emulsions as compared to natural
      soybean PC in MCT and soybean oil.

PMID- 16637691
TI  - Sonication-assisted extraction of chitin from shells of fresh water prawns
      (Macrobrachium rosenbergii).
AB  - The effect of sonication during chitin extraction from freshwater prawn shells on
      yield, purity, and crystallinity of chitin was investigated. Dry prawn shells
      were suspended for 4 h in 0.25 M HCl at 40 degrees C while they were sonicated
      for 0, 1, and 4 h. Demineralized shells were lyophilized, resuspended in 0.25 M
      NaOH, and sonicated again for 0, 1, and 4 h for protein removal. The yield of
      chitin decreased from 8.28 to 5.02% for nonsonicated and sonicated samples,
      respectively, which was attributed to losses of depolymerized materials in the
      wash water. The application of ultrasound enhanced the removal of proteins. In
      nontreated shells, the amount of protein was 44.01% and was reduced to 12.55,
      10.59, and 7.45% after 0, 1, and 4 h of sonication treatments. The glucosamine
      content slightly decreased with sonication probably because of losses due to
      depolymerization. The crystallinity indices of chitins decreased as the time of
      sonication increased. The degree of acetylation of chitins was unaffected by
      sonication, but the degree of acetylation of chitosans produced from sonicated
      chitin decreased from 70.0 to 68.7 and 61.4% for 1 and 4 h sonicated samples,
      respectively.

PMID- 16637692
TI  - Possible role for cryostabilizers in preventing protein and lipid alterations in
      frozen-stored minced muscle of Atlantic mackerel.
AB  - Adding DE 18 maltodextrin (80 g kg(-1)) to high-fat minced mackerel was highly
      effective against lipid oxidation and protein and color changes during frozen
      storage. It increased the temperature of ice-melting onset (Tm') and decreased
      freeze concentration of solutes in the unfrozen water (UFW) phase, which would
      have allowed it to effectively slow such perturbations. This maltodextrin showed
      a higher effectiveness against lipid oxidation, but was slightly less effective
      in preventing the loss of protein solubility than common cryoprotectants, that
      is, an equiproportional mixture of sucrose and sorbitol. Such differences in
      effectiveness were much higher in low-fat minces, in which lipid oxidation
      proceeded to a much lower extent. Consequently, prior to replacing traditional
      cryoprotectants with maltodextrins, it should be known which processes limit the
      shelf life of the food. Decreasing (from 80 to 50 g kg(-1)) the proportion of
      maltodextrin added to high-fat minced mackerel showed that although it affected
      only slightly the effectiveness against lipid oxidation, it did notably affect
      the effectiveness in preventing the loss of protein solubility and color changes.
      Therefore, such a decrease could be accepted only if lipid oxidation is the most
      limiting process of shelf life, but does not seem appropriate when protein
      changes are important.

PMID- 16637693
TI  - Metabolic changes of Malvasia grapes for wine production during postharvest
      drying.
AB  - Malvasia (Vitis vinifera L.) grapes were harvested at 17.8% of soluble solids
      content (SSC) and placed inside an innovative dehydration room where temperature,
      relative humidity, and air flow were maintained, respectively, at 15 degrees C,
      40%, and 1-1.5 m s(-1). Weight loss of bunches reached approximately 33% in 29
      days. SSC increased inversely proportionally with the weight decrease, reaching
      at the end of experiment 23%. Abscisic acid (ABA) increased rapidly from around
      29 to 80 microg g(-1) of dry weight at 11.7% of bunch weight loss and then
      declined gradually. Lipoxygenase (LOX) showed the same behavior as ABA, whereas
      alcohol dehydrogenase (ADH), read in the way of ethanol oxidation, increased
      continuously when the weight loss reached approximately 19.5%. In parallel with
      the activity of LOX, C6 compound [hexanal, hex-1-enol, (E)-hex-2-enal]
      concentrations reached a peak at 11.7% of weight loss, whereas ethanol and
      acetaldehyde increased with the increase of ADH and successively decrease and
      ethyl acetate increased. Proline increased initially as ABA and successively with
      the increase of ADH, 5.3-fold increase versus 4.2-fold increase of proteins.
      Postharvest dehydration of Malvasia grapes shows a biphasic pattern: a first
      metabolic stress response up to 11.7% of bunch weight loss and a second stress
      response beyond 19.5% of weight loss. The metabolic mechanism of these
      postharvest water stress responses is discussed.

PMID- 16637694
TI  - Effects of fertilization, crop year, variety, and provenance factors on mineral
      concentrations in onions.
AB  - Mineral concentrations of onions (Allium cepa L.) grown under various conditions,
      including factors (fertilization, crop year, variety, and provenance), were
      investigated to clarify how much each factor contributes to the variation of
      their concentrations. This was because the mineral concentrations might be
      affected by various factors. The ultimate goal of this study was to develop a
      technique to determine the geographic origins of onions by mineral composition.
      Samples were onions grown under various conditions at 52 fields in 18 farms in
      Hokkaido, Japan. Twenty-six elements (Li, Na, Mg, Al, P, K, Ca, Mn, Fe, Co, Ni,
      Cu, Zn, Rb, Sr, Y, Mo, Cd, Cs, Ba, La, Ce, Nd, Gd, W, and Tl) in these samples
      were determined by inductively coupled plasma atomic emission spectrometry and
      inductively coupled plasma mass spectrometry. Fertilization conditions and crop
      years of onions caused variations of P, Ni, Cu, Rb, Sr, Mo, Cs, and Tl
      concentrations in onions; different onion varieties also showed variations in
      numerous element concentrations. However, the variations of mineral compositions
      of onions by these factors were smaller than the differences between production
      places with a few exceptions. Furthermore, Na, Rb, and Cs in group IA of the
      periodic table, Ca, Sr, and Ba in group IIA, and Zn and Cd in group IIB showed
      similar concentration patterns by group; this result demonstrated that elements
      in the same periodic groups behaved similarly in terms of their absorption in
      onions.

PMID- 16637695
TI  - Quantification of tocopherols and tocotrienols in portuguese olive oils using
      HPLC with three different detection systems.
AB  - Three different HPLC detection systems were compared for the determination of
      tocopherols and tocotrienols in olive oil: fluorescence and diode array connected
      in series, ultraviolet, and evaporative light scattering. The best results were
      obtained with the fluorescence detector, which was successfully applied in the
      quantification of tocopherols and tocotrienols in 18 samples of Portuguese olive
      oils. To support the validity of the method, the parameters evaluated were
      linearity, detection limits, repeatability, and recovery. All of the studied
      samples showed similar qualitative profiles with six identified compounds: alpha
      T, beta-T, gamma-T, delta-T, alpha-T3, and gamma-T3. Alpha-tocopherol (alpha-T)
      was the main vitamin E isomer in all samples ranging from 93 to 260 mg/kg. The
      total tocopherols and tocotrienols ranged from 100 to 270 mg/kg. Geographic
      origin did not seem to influence the tocopherol and tocotrienol composition of
      the olive oils under evaluation.

PMID- 16637696
TI  - Simulated glyphosate drift influences nitrate assimilation and nitrogen fixation
      in non-glyphosate-resistant soybean.
AB  - Nontarget injury from glyphosate drift is a concern among growers using non
      glyphosate-resistant (non-GR) cultivars. The effects of glyphosate drift on
      nitrate assimilation and nitrogen fixation potential, nodule mass, and yield of
      non-GR soybean were assessed in a field trial at Stoneville, MS. A non-GR soybean
      cultivar 'Delta Pine 4748S' was treated with glyphosate at 12.5% of use rate of
      0.84 kg of active ingredient/ha at 3 (V2), 6 (V7), and 8 (R2, full bloom) weeks
      after planting (WAP) soybean to simulate glyphosate drift. Untreated soybean was
      used as a control. Soybeans were sampled weekly for 2 weeks after each glyphosate
      treatment to assess nitrate assimilation and N2 fixation potential. Nitrate
      assimilation was assessed using in vivo nitrate reductase assay in leaves, stems,
      roots, and nodules. Nitrogen fixation potential was assessed by measuring
      nitrogenase activity using the acetylene reduction assay (ARA). Nitrogen content
      of leaves, shoots, and seed and soybean yield were also determined. In the first
      sampling date (4 WAP), glyphosate drift caused a significant decrease in NRA in
      leaves (60%), stems (77%), and nodules (50%), with no decrease in roots. At later
      growth stages, NRA in leaves was more sensitive to glyphosate drift than stems
      and roots. Nitrogenase activity was reduced 36-58% by glyphosate treatment at 3
      or 6 WAP. However, glyphosate treatment at 8 WAP had no effect on nitrogenase
      activity. Nitrogen content was affected by glyphosate application only in shoots
      after the first application. No yield, seed nitrogen, protein, or oil
      concentration differences were detected. These results suggest that nitrate
      assimilation and nitrogen fixation potential were significantly reduced by
      glyphosate drift, with the greatest sensitivity early in vegetative growth.
      Soybean has the ability to recover from the physiological stress caused by
      glyphosate drift.

PMID- 16637697
TI  - Insect nicotinic acetylcholine receptors: neonicotinoid binding site specificity
      is usually but not always conserved with varied substituents and species.
AB  - The diversity of neonicotinoid insecticides acting as insect nicotinic
      acetylcholine (ACh) receptor (nAChR) agonists is illustrated by imidacloprid
      (IMI) with chloropyridinylmethyl (CPM) and N-nitroimine substituents, dinotefuran
      (DIN) with tetrahydrofurylmethyl (TFM) and N-nitroimine moieties, and acetamiprid
      (ACE) with CPM and N-cyanoimine groups. These three neonicotinoids are used here
      as radioligands to test the hypothesis that they all bind to the same site in the
      same way in both fruit flies (Drosophila melanogaster) and a leafhopper pest
      (Homalodisca coagulata): that is, neonicotinoid binding site specificity is
      conserved in the insect nAChRs. Multiple approaches show that [3H]IMI and [3H]ACE
      interact with an identical site in both species. However, although [3H]DIN binds
      with high affinity in both insects, its pharmacological profile in Homalodisca is
      surprisingly unique, with high sensitivity to some TFM-containing compounds and
      ACh. The TFM moiety of DIN may bind in a different orientation compared to the
      CPM group of IMI and ACE.

PMID- 16637698
TI  - Influence of thaxtomins in different combinations and concentrations on growth of
      micropropagated potato shoot cultures.
AB  - Plant-pathogenic Streptomyces species produce a variety of different phytotoxic 4
      nitroindol-3-yl-containing 2,5-dioxopiperazines (thaxtomins) that induce scab
      symptoms on potato tubers (Solanum tuberosum). The possible mutual synergistic or
      antagonistic effects of thaxtomins are unknown. Modified methodology using column
      chromatography allowed the purification of thaxtomin A in large quantities (27
      mg, HPLC purity of 97%). Thaxtomin A ortho isomer, thaxtomin B, and C-14
      deoxythaxtomin B (thaxtomin D) were also purified. All four compounds induced
      similar symptoms of reduced root and shoot growth, root swelling (10-200 ppb), or
      necrosis (200-1000 ppb) on micropropagated in vitro cultures of potato. The scab
      resistant potato cvs. Sabina and Nicola were more tolerant to thaxtomins than was
      the scab-susceptible cv. Matilda. Thaxtomins applied in combinations showed
      additive effects but no synergism, whereas thaxtomins A and B displayed
      antagonism with thaxtomin A ortho isomer.

PMID- 16637699
TI  - Sensory-directed identification of taste-active ellagitannins in American
      (Quercus alba L.) and European oak wood (Quercus robur L.) and quantitative
      analysis in bourbon whiskey and oak-matured red wines.
AB  - Aimed at increasing our knowledge on the sensory-active nonvolatiles migrating
      from oak wood into alcoholic beverages upon cooperaging, an aqueous ethanolic
      extract prepared from oak wood chips (Quercus alba L.) was screened for its key
      taste compounds by application of the taste dilution analysis. Purification of
      the compounds perceived with the highest sensory impacts, followed by liquid
      chromatography/mass spectrometry as well as one-dimensional and two-dimensional
      NMR experiments, revealed the ellagitannins vescalagin, castalagin, and
      grandinin, the roburins A-E, and 33-deoxy-33-carboxyvescalagin as the key
      molecules imparting an astringent oral sensation. To the best of our knowledge,
      33-deoxy-33-carboxyvescalagin has as yet not been reported as a phytochemical in
      Q. alba L. In addition, the sensory activity of these ellagitannins was
      determined for the first time on the basis of their human threshold
      concentrations and dose/response functions. Furthermore, the ellagitannins have
      been quantitatively determined in extracts prepared from Q. alba L. and Quercus
      robur L., respectively, as well as in bourbon whiskey and oak-matured red wines,
      and the sensory contribution of the individual compounds has been evaluated for
      the first time on the basis of dose/activity considerations.

PMID- 16637700
TI  - Comparison of odor-active volatile compounds of fresh and smoked salmon.
AB  - The odorant volatile compounds of raw salmon and smoked salmon have been
      investigated by two gas chromatography-olfactometry methods (frequency detection
      and odorant intensity) and gas chromatography-mass spectrometry. After
      simultaneous steam distillation-solvent extraction with diethyl ether and the
      recovery of the aromatic extract in ethanol, qualitative olfactometric
      characterization and identification followed by a quantitative assessment of the
      odorant volatile compounds were carried out. The origin of many odorant compounds
      of smoked salmon can be attributed to wood smoke. Another part of smoked salmon
      aroma is due either to the odorant compounds of the raw fish flesh or to an
      evolution of fish flesh aroma thanks to the smoking process conditions. Forty
      nine odorant compounds have been identified in fresh salmon and 74 in smoked
      salmon. Carbonyl compounds, such as heptanal or (E,Z)-2,6-nonadienal, show a high
      detection frequency and odorant intensity in unsmoked fish, giving the flesh its
      typical fishy odor. For smoked salmon, phenolic compounds, such as cresol or
      guaiacol, and furanic compounds seem to be responsible for the smoked odor.

PMID- 16637701
TI  - Redox instability induced by 4-hydroxy-2-nonenal in porcine and bovine myoglobins
      at pH 5.6 and 4 degrees C.
AB  - Myoglobin (Mb) redox stability affects meat color and is compromised by lipid
      oxidation products such as 4-hydroxy-2-nonenal (HNE). Pork lipids are generally
      more unsaturated and would be expected to oxidize readily and produce more
      oxidation products than beef. Supranutritional supplementation of vitamin E
      improves Mb redox stability of beef but not pork. The present study investigated
      HNE-induced redox instability in porcine and bovine myoglobins at 4 degrees C and
      pH 5.6. Oxymyoglobin (OxyMb) was incubated with HNE (0.075 mM porcine OxyMb + 0.5
      mM HNE; 0.15 mM bovine OxyMb + 1.0 mM HNE). In porcine Mb, only monoadducts
      formed via Michael addition were detected after 72 h, whereas in bovine Mb both
      mono- and diadducts were identified. LC-MS-MS identified four histidine residues
      (His 36, 81, 88, and 152) of bovine Mb that were readily adducted by HNE, whereas
      in porcine Mb only two histidine residues (His 24 and 36) were adducted. These
      results suggested that the primary structure of bovine Mb predisposes it to
      greater nucleophilic attack by HNE and subsequent adduction than is suffered by
      porcine Mb.

PMID- 16637702
TI  - Effects of heat and high hydrostatic pressure treatments on disulfide bonding
      interchanges among the proteins in skim milk.
AB  - Traditionally, milk has been heat treated to control microorganisms and to alter
      its functionality, for example, to increase its heat stability. Pressure
      treatment has been considered as a possible alternative for microorganism
      control, but some of the functionality-related milk protein interactions have not
      been explored. The present study used two novel two-dimensional polyacrylamide
      gel electrophoresis (2D PAGE) methods to explore the differences in the
      irreversible disulfide bond changes among the milk proteins after four common
      heat treatments and after 30-min pressure treatments of milk at 200, 400, 600,
      and 800 MPa at ambient temperature (22 degrees C). The pasteurizing heat
      treatment (72 degrees C for 15 s) denatured and aggregated only a few minor whey
      proteins, but the high heat treatments (100 degrees C for 120 s, 120 degrees C
      for 120 s, and 140 degrees C for 5 s) formed disulfide-bonded aggregates that
      included a high proportion of all of the whey proteins and kappa-casein (kappa
      CN) and a proportion of the alpha(s2)-CN. Pressure treatment of milk at 200 MPa
      caused beta-lactoglobulin (beta-LG) to form disulfide-bonded dimers and
      incorporated beta-LG into aggregates, probably disulfide-bonded to kappa-CN. The
      other whey proteins appeared to be less affected at 200 MPa for 30 min. In
      contrast, pressure treatment at 800 MPa incorporated beta-LG and most of the
      minor whey proteins, as well as kappa-CN and much of the alpha(s2)-CN, into
      aggregates. The accessibility of alpha(s2)-CN and formation of complexes
      involving alpha(s2)-CN, kappa-CN, and whey proteins in the pressure treated milk
      is an important novel finding. However, only some of the alpha-lactalbumin was
      denatured or incorporated into the large aggregates. These and other results show
      that the differences between the stabilities of the proteins and the
      accessibilities of the disulfide bonds of the proteins at high temperature or
      pressure affect the formation pathways that give the differences among the
      resultant aggregates, the sizes of the aggregates, and the product
      functionalities.

PMID- 16637703
TI  - Effects of oxygen and turmeric on the formation of oxidative aldehydes in fresh
      pack dill pickles.
AB  - Hexanal, pentanal, and heptanal were found to be normal components of
      commercially processed, fresh-pack dill pickles. Hexanal and pentanal were
      present at concentrations severalfold higher than their odor detection
      thresholds. These aldehydes were also found in pickles that were packed in the
      laboratory under anaerobic conditions. Injection of oxygen into pickles prepared
      in anaerobic conditions resulted in the production of increasing the amounts of
      hexanal, heptanal, and pentanal. Hexanal, pentanal, (E)-2-hexenal, and heptanal
      levels were negatively correlated with the addition of turmeric in dill pickles
      with oxygen injected into the jar, indicating that the curcumin present in
      turmeric is an effective antioxidant in this product. At commercial coloring
      levels (250 mg/L), turmeric addition maintained aldehyde levels near the
      concentrations found in commercial fresh-pack pickles packaged in glass
      containers when oxygen was added in amounts comparable to that which would enter
      a plastic container during a 1-year storage period. Therefore, the addition of
      turmeric appears to be an effective approach to minimize the formation of
      oxidative off-flavors in pasteurized dill pickles that may result from the oxygen
      permeability of plastic containers.

PMID- 16637704
TI  - Characterization of galactomannan derivatives in roasted coffee beverages.
AB  - In this work, the galactomannans from roasted coffee infusions were purified by
      50% ethanol precipitation, anion exchange chromatography, and phenylboronic acid
      immobilized Sepharose chromatography. Specific enzymatic hydrolysis of the beta
      (1-->4)-D-mannan backbone allowed us to conclude that the galactomannans of
      roasted coffee infusions are high molecular weight supports of low molecular
      weight brown compounds. Also, the molecular weight of the brown compounds linked
      to the galactomannan increases with the increase of the coffee degree of roast.
      The reaction pathways of galactomannans during the coffee roasting process were
      inferred from the detection of specific chemical markers by gas chromatography
      electron impact mass spectrometry and/or electrospray ionization tandem mass
      spectrometry. Maillard reaction, caramelization, isomerization, oxidation, and
      decarboxylation pathways were identified by detection of Amadori compounds, 1,6
      beta-anhydromannose, fructose, glucose, mannonic acid, 2-ketogluconic acid, and
      arabinonic acid in the reducing end of the obtained oligosaccharides. The
      implication of the several competitive reaction pathways is discussed and related
      to the structural changes of the galactomannans present in the roasted coffee
      infusions.

PMID- 16637705
TI  - Se-enriched mycelia of Pleurotus ostreatus: distribution of selenium in cell
      walls and cell membranes/cytosol.
AB  - The incorporation of Se to fungi has been studied, focusing on element
      distribution among different cellular compartments and, in particular,
      polysaccharide structures contained in cell walls. Se-enriched mycelia of
      Pleurotus ostreatus were obtained in submerged cultures. The incorporation of
      selenium from the growth medium to mycelia was observed with the relative
      distribution between cytosol plus cell membranes fraction (CCM) and cell walls
      fraction (CW) of about 44 and 56%, respectively. CCM fractions were analyzed by
      size exclusion chromatography with on-line UV (280 nm) and ICP-MS detection
      (80Se). The results obtained showed selenium binding to components of different
      molecular masses (about 24% of total selenium coeluted with the compounds of
      molecular mass > 10 kDa). A polysaccharide-containing fraction of mycelia was
      treated alternatively with Tris-HCl at pH 7.5 or with chitinase. Better
      solubility and increased contribution of low molecular mass compounds were
      observed in chitinase extracts (UV detection), confirming the degradation of
      polysacharides by the enzyme. The total area under the ICP-MS chromatogram of
      chitinase extract was 2 times higher with respect to the area for Tris-HCl
      extract. Furthermore, the relative contribution of selenium in the low molecular
      mass fraction (molecular mass < 1 kDa) in chitinase extract was 72% as compared
      to 45% in Tris-HCl extract (based on peak area measurements with respect to total
      area under the chromatogram). The results obtained suggest selenium binding to
      chitin-containing polysaccharide structures in fungi cell walls.

PMID- 16637706
TI  - Molecular mechanism of antioxidant synergism of tocotrienols and carotenoids in
      palm oil.
AB  - During repeated deep-fat frying of potato slices at 163 degrees C in yellow or
      red palm olein of comparable fatty acid profiles, the oxidative stability
      (peroxide value and anisidine value) of the palm oleins was similar, and in
      yellow palm olein, the rate of antioxidant depletion decreased in the order gamma
      T3 > alpha-T3 > delta-T3 (T3, tocotrienol). In red palm olein, which had a total
      tocopherol/tocotrienol content of 1260 vs 940 ppm in yellow palm olein and a
      corresponding longer induction period in the Rancimat stability test at 120
      degrees C, only depletion of gamma-T3 was significant among the phenols during
      frying and slower as compared to that in yellow palm olein. The carotenes in the
      red palm olein were depleted linearly with the number of fryings, apparently
      yielding an overall protection of the phenols. In antioxidant-depleted palm olein
      and in phospholipid liposomes with added increasing concentrations of phenols,
      gamma-T3 was found to be a better antioxidant than alpha-T3. alpha-T3 and alpha-T
      (T, tocopherol) had a similar antioxidant effect in antioxidant-depleted palm
      olein in the Rancimat stability test, while in the liposomes the ordering as
      determined by induction period for the formation of conjugated dienes was gamma
      T3 > alpha-T3 > alpha-T. The addition of 100-1000 ppm beta-carotene to
      antioxidant-depleted palm olein or liposomes (lycopene also tested) did not
      provide any protection against oxidation. In the liposomes, synergistic
      interactions were observed between beta-carotene or lycopene and alpha-T, alpha
      T3, or gamma-T3 for carotene/phenol ratios of 1:10 and 1:2 but not for 1:1. In
      chloroform, carotenes were regenerated by tocopherols/tocotrienols from carotene
      radicals generated by laser flash photolysis as shown by transient absorption
      spectroscopy, suggesting that carotenes rather than phenols are the primary
      substrate for lipid-derived radicals in red palm olein, in effect depleting
      carotenes prior to phenols during frying. Regeneration of carotenes by the
      phenols also explains the synergism in liposomes. In the laser flash photolysis
      experiments, gamma-T3 was also found to be faster in regenerating carotenes than
      alpha-T3 and alpha-T.

PMID- 16637707
TI  - Metabolism of the food-associated carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine by human intestinal microbiota.
AB  - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a putative human carcinogenic
      heterocyclic aromatic amine formed from meat and fish during cooking. Although
      the formation of hazardous PhIP metabolites by mammalian enzymes is well
      documented, nothing is known about the PhIP transformation potency of human
      intestinal bacteria. In this study, the in vitro metabolism of PhIP by human
      fecal samples was investigated. Following anaerobic incubation of PhIP with
      stools freshly collected from six healthy volunteers, we found that PhIP was
      extensively transformed by the human intestinal bacteria. HPLC analysis showed
      that the six human fecal microbiota transformed PhIP with efficiencies from 47 to
      95% after 72 h incubation, resulting in one major derivative. ESI-MS/MS, HRMS, 1D
      (1H, 13C, DEPT) and 2D (gCOSY, gTOCSY, gHMBC, gHSQC) NMR, and IC analysis
      elucidated the complete chemical identity of the microbial PhIP metabolite as 7
      hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido[3',2':4,5]imidazo[1,2
      a]pyrimidin-5-ium chloride. At present, no information is available about the
      biological activity of this newly discovered bacterial PhIP metabolite. Our
      findings however suggest that bacteria derived from the human intestine play a
      key role in the activation or detoxification of PhIP, a digestive fate ignored so
      far in risk assessments. Moreover, the variation in transformation efficiency
      between the human microbiota indicates interindividual differences in the ability
      to convert PhIP. This may predict individual susceptibility to carcinogenic risk
      from this suspected dietary carcinogen.

PMID- 16637708
TI  - Common sources and estimated intake of plant sterols in the Spanish diet.
AB  - Plant sterols (PS) are minor lipid components of plants, which may have potential
      health benefits, mainly based in their cholesterol-lowering effect. The aim of
      this study was to determine the composition and content of PS in plant-based
      foods commonly consumed in Spain and to estimate the PS intake in the Spanish
      diet. For this purpose, the determination of PS content, using a modern
      methodology to measure free, esterified, and glycosidic sterol forms, was done.
      Second, an estimation of the intake of PS, using the Spanish National Food
      Consumption data, was made. The daily intake per person of PS--campesterol, beta
      sitosterol, stigmasterol, and stigmastanol--in the Spanish diet was estimated at
      276 mg, the largest component being beta-sitosterol (79.7%). Other unknown
      compounds, tentatively identified as PS, may constitute a considerable potential
      intake (99 mg). When the daily PS intake among European diets was compared in
      terms of campesterol, beta-sitosterol, stigmasterol, and stigmastanol, the PS
      intake in the Spanish diet was in the same range of other countries such as
      Finland (15.7% higher) or The Netherlands (equal). However, some qualitative
      differences in the PS sources were detected, that is, the predominant brown bread
      and vegetable fat consumption in the northern diets versus the white bread and
      vegetable oil consumption in the Spanish diet. These differences may help to
      provide a link between the consumption of PS and healthy effects of the diet.

PMID- 16637709
TI  - DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF
      kappaB activation in RAW 264.7 macrophages.
AB  - Diallyl trisulfide (DATS), diallyl sulfide (DAS), and diallyl disulfide (DADS)
      are the three major organosulfur compounds (OSCs) in garlic oil. In contrast to
      DADS and DATS, evidence of an anti-inflammatory effect of DATS is limited. In
      this study compares the efficacy of DATS with those of DAS and DADS on
      lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS)
      expression and nitric oxide (NO) production in RAW 264.7 macrophages. The NO
      production in LPS-activated RAW 264.7 macrophages was suppressed by both DADS and
      DATS in a dose-dependent manner. At 100 muM, the nitrite levels of DADS- and DATS
      treated cells were 57 and 34%, respectively, of cells treated with LPS alone.
      DAS, however, had no influence on NO production even at a concentration of 1 mM.
      Western blot and Northern blot assays showed that DADS and DATS but not DAS dose
      dependently suppressed LPS-induced iNOS protein and mRNA expression in a pattern
      similar to that noted for NO production. LPS-induced cellular peroxide production
      was significantly inhibited by DADS and DATS (P < 0.05) but not by DAS.
      Electrophoresis mobility shift assays further indicated that DADS and DATS
      effectively inhibited the activation of NF-kappaB induced by LPS. Taken together,
      these results indicate that the differential efficacy of three major OSCs of
      garlic oil on suppression of iNOS expression and NO production is related to the
      number of sulfur atoms and is in the order DATS > DADS > DAS. The inhibitory
      effect of DATS on LPS-induced iNOS expression is likely attributed to its
      antioxidant potential to inhibit NF-kappaB activation.

PMID- 16637710
TI  - Mycoflora and multimycotoxin detection in corn silage: experimental study.
AB  - Agricultural activities involve the use of crop preservation such as "trench
      type" silo, which can sometimes be contaminated by fungi. To investigate the
      exposure of livestock and farm workers to fungal spores and mycotoxins, a
      multimycotoxin analysis method has been developed. Six mycotoxins (aflatoxin B1,
      citrinin, deoxynivalenol, gliotoxin, ochratoxin A, and zearalenone) were
      quantified by high-performance liquid chromatography coupled to mass spectrometry
      after solid-phase extraction. An experimental study of fungal species and
      mycotoxins was conducted in corn silage (Normandy, France) during 9 months of
      monitoring. The results indicated the recurrence of around 20 different species,
      with some of them being potentially toxigenic fungi such as Aspergillus
      fumigatus, Aspergillus parasiticus, Fusarium verticillioides, and Monascus ruber,
      and the detection of aflatoxin B1 (4-34 ppb), citrinin (4-25 ppb), zearalenone
      (23-41 ppb), and deoxynivalenol (100-213 ppb). This suggested a possible chronic
      exposure to low levels of mycotoxins.

PMID- 16637711
TI  - Surgically assisted rapid maxillary expansion compared with orthopedic rapid
      maxillary expansion.
AB  - The objective of this study is to evaluate and compare the dental and skeletal
      changes occurring during orthopedic rapid maxillary expansion (RME) and
      surgically assisted RME during the active phase of treatment. The study was
      divided into two groups. The first group of 10 patients (six males, four females;
      mean age, 15.51 years) received orthopedic RME. The second group of 10 patients
      (seven males, three females; average age: 19.01 years) received surgically
      assisted RME (SARME). All patients underwent maxillary expansion with occlusal
      coverage Hyrax-type expanders activated two turns a day (0.25 mm per turn).
      Preexpansion and postexpansion lateral and posteroanterior cephalograms were
      obtained for each patient. Statistically significant differences between the
      SARME and RME groups were found in the N-ANS, SN/ PP (P < .01) and SNA, SNB,
      mandibular dentoalveolar, and maxillary bony base (P < .05) measurements.
      Clinically, there is no difference in patient response between the RME and SARME
      groups. The only difference between the groups was their indication for RME or
      SARME, which is based on the age and skeletal maturation of the patient.

PMID- 16637712
TI  - Skeletal and dental effects of a mini maxillary protraction appliance.
AB  - The aim of this study was to evaluate the skeletal and dentoalveolar changes
      achieved by a modified protractor in growing skeletal and dental Class III
      patients and to compare these changes with normal growth in a Class I untreated
      control group. The study group consisted of 25 patients (11 girls, 14 boys; mean
      age 11.74 +/- 1.81 years). The control group was composed of 20 patients (15
      girls, five boys; mean age 11.89 +/- 1.08 years). The Class III patients were
      treated with a bonded acrylic cap splint type expander and a modified maxillary
      protractor until a positive overjet was achieved. The mean observation period was
      0.65 years. Changes in study and control groups and differences between the
      groups were analyzed statistically. The results showed that protraction appliance
      produced a significant positive improvement in maxillo-mandibular relations. The
      forward movement of the maxilla was significant in treated Class III patients,
      but a slight difference was present between the two groups regarding maxillary
      rotation. The effective length of the maxilla was significantly increased in the
      Class III patients. The mandible was positioned backward, and posterior rotation
      of the mandible was significant in the treatment group. There was a significant
      increase in lower anterior facial height of treated Class III patients. The
      dentoalveolar measurements showed that the maxillary incisors proclined and the
      mandibular incisors significantly retroclined in the Class III group. A modified
      maxillary protractor treatment is effective for correcting skeletal Class III
      malocclusion.

PMID- 16637713
TI  - Microscopic evaluation of mandibular symphyseal distraction osteogenesis.
AB  - The purpose of this study was to evaluate microscopically the newly formed hard
      tissue after a consolidation period of mandibular symphyseal distraction
      osteogenesis (MSDO). Sixteen patients underwent MSDO treatment. After a latency
      period of seven days, the distraction device was activated by the patient once in
      the morning and once in the evening, for a total of one mm per day for a mean
      10.1 +/- 2.8 days, and the mean opening of the device was 8.1 +/- 1.7 mm. The
      device was usually maintained in position approximately 90 days after surgery.
      After the completion of the distraction period, the lower anterior teeth were
      bonded and tooth movement into the distraction site was initiated. After a
      consolidation period, second surgery was performed to remove the distraction
      devices. During the second surgery, hard tissue biopsies were taken on the apical
      region of the two central incisors and the left canine. The samples were fixed in
      10% buffered formalin and decalcified in 3% HNO(3) solutions. New bone formation
      was present within the distraction gap immediately after the consolidation
      period. The cellular construction was more irregular in the distraction sections
      than in the normal bone sections. The newly distracted area was not complete
      immediately after the consolidation period. Furthermore, the newly formed bone
      had a membranous structure, which indicates continual maturation. Bone exposed to
      stretching forces undergoes new bone formation, and the newly formed bone is of a
      membranous type also named as a woven type.

PMID- 16637714
TI  - Interexaminer reliability of two cephalometric methods to determine proximal
      segment position after bilateral sagittal split ramus osteotomy.
AB  - The objective of this study was to evaluate the interexaminer reliability of two
      cephalometric methods for determining positional change of the proximal segment
      after a bilateral sagittal split ramus osteotomy (BSSRO) for mandibular
      advancement. The records of 25 patients were used in a double-blind trial. Two
      nontrained investigators (having read the articles describing the two
      cephalometric methods, but with no other special training) independently traced
      posterior-anterior (PA) and lateral cephalometric radiographs taken at three time
      intervals: (T1) before surgery, (T2) immediately after surgery, and (T3) after
      orthodontic treatment was completed. The level of agreement between the two
      investigators (interexaminer reliability) on all 25 patients was estimated by
      calculating the intraclass correlation coefficient (ICC). The ICC was found to
      have a high value, indicating "substantial" to "almost perfect agreement" between
      the two examiners. Thus the results validate the use of these two methods to
      determine proximal segment positional changes in the frontal and sagittal planes
      of space after a BSSRO.

PMID- 16637715
TI  - Noncompliance unilateral maxillary molar distalization:.
AB  - The aim of this prospective study was the three-dimensional (3-D) analysis of
      tooth movements after unilateral upper molar distalization by means of a
      noncompliance intraoral appliance, the Keles slider. This appliance exerts a
      distalizing force of 150 g at approximately the level of the center of resistance
      of the upper first molar. Twelve patients (six girls and six boys with a mean age
      of 13.1 years) with a unilateral Class II molar relationship participated in the
      study. Dental casts were taken immediately before placement and after removal of
      the appliance. The casts were digitized using a 3-D surface laser scanner and
      superimposed on a predefined area of the palate. The average unilateral upper
      first molar distal movement was 3.1 mm (range: 2.4 to 5.3 mm). Anchorage loss was
      expressed by a 2.1 mm (range: 0.8 to 3.8 mm) proclination of the central incisors
      and a 6.1 degrees mesial inclination of the ipsilateral first premolar (range:
      1.7 degrees to 12.3 degrees ). There was approximately 1 mm of midline deviation
      toward the contralateral side and a 1.6 mm (range: 0.8 to 2.3 mm) buccal
      displacement of the contralateral first premolar. A substantial variation was
      observed among patients. Noncompliance unilateral upper molar distalization was
      an efficient treatment approach. There was, however, a substantial anchorage
      loss. Case selection is strongly recommended because significant anterior
      crowding, ectopic canines, or spacing can lead to significant anchorage loss.

PMID- 16637716
TI  - Validity of panoramic radiographs for measuring mandibular asymmetry.
AB  - The objective of this study is to evaluate the accuracy of panoramic radiographs
      for diagnosing vertical asymmetry of the posterior mandible. The first part of
      the study used a model to evaluate the reproducibility of this particular
      panoramic machine. The tube traverse did not significantly affect the linear
      measurements, but the side of the machine where the structure was located
      produced an average of 2.1% variation in the total height of the mandible. In the
      second part of the study, the left-right (%) differences were measured on the
      panoramics and the laminographs of five skulls with lead markers. These
      differences were compared with the percent difference measured directly on the
      skull and with each other and suggested that the laminograph could be used as the
      "gold standard" for measuring posterior vertical mandibular asymmetry. The third
      part of the study evaluated a patient sample (N = 42). The correlation
      coefficient between the two types of films was determined to be 0.92 for total
      height and 0.39 for condyle height. Using the 6% cutoff reported in the
      literature, the sensitivity of the panoramics to diagnose asymmetry for the total
      height was determined to be 0.62 and the specificity 1.0. This study suggests
      that the panoramic radiograph can be used to evaluate vertical posterior
      mandibular asymmetry, but there will be some underdiagnosis.

PMID- 16637717
TI  - Reproducibility of cephalometric measurements made by three radiology clinics.
AB  - The purpose of this study was to assess reproducibility of cephalometric
      measurements in cephalograms obtained by three dentomaxillofacial radiology
      clinics. Forty lateral cephalometric radiographs were selected and sent at
      different times to three different clinics for cephalometric analyses. Each
      clinic digitized the radiographs with the same resolution, and landmarks were
      located with the mouse pointer directly on the digitized radiographic image on
      the screen. Three cephalograms were obtained from each radiograph, totaling 120
      analyses. Data were analyzed with analysis of variance. Of the 32 factors
      studied, reproducibility of results was satisfactory for only four factors:
      position of maxilla relative to anterior cranial base, inclination of occlusal
      plane relative to anterior cranial base, position of lower incisor relative to
      nasion-pogonion line, and soft-tissue profile of face (P < .05). Differences in
      cephalometric measurements were present and such differences were significant for
      most factors analyzed. The different cephalometric measurements obtained by the
      three dental radiology clinics were not reproducible.

PMID- 16637718
TI  - Initial effects of the tongue crib on tongue movements during deglutition: a Cine
      Magnetic resonance imaging study.
AB  - The objective of this study was to investigate the initial effects of a tongue
      crib on tongue movements during deglutition by using real time balanced turbo
      field echo (B-TFE) Cine-MR imaging. A total of 21 patients were evaluated in this
      study. The open-bite group (OBG) consisted of 11 patients (seven girls, four
      boys) who had a mean age of 11.09 +/- 2.02 years and a mean overbite of -5.14 +/-
      1.83 mm. These patients were evaluated initially (T1) and while wearing a tongue
      crib (T2). A total of 10 patients (five girls, five boys) with a mean age of 14.5
      +/- 2.6 years and with a mean overbite of 1.6 +/- 0.5 mm served as controls (CG),
      and only initial records were obtained from these patients. T2 was compared with
      T1 and CG. T1 was also compared with CG. We evaluated deglutition during three
      stages matching oral (1), pharyngeal (2), and esophageal (3) stages. Our results
      indicated that the tongue's tip positioned more posteriorly when the crib was in
      place (T2) compared with both T1 and CG; the anterior portion of the tongue's
      dorsum was at a lower position in T2 compared with both T1 and CG at stage 3; the
      midportion of the tongue's dorsum was at a lower position in T2 than in T1 and CG
      at stages 1 and 2. To compensate for the posterior position of the tongue's tip
      (caused by the tongue crib), adaptive changes occurred in the anterior and
      midportions of the dorsum of the tongue.

PMID- 16637719
TI  - Racial variations in cephalometric analysis between Whites and Kuwaitis.
AB  - The objective of this study is to determine whether (1) Kuwaiti adolescents
      differ from Caucasian adolescents with respect to their cephalometric values; (2)
      sex plays a role in the differences between the two groups; and (3) a need exists
      to develop cephalometric standards for the Kuwaiti population. Standardized
      cephalometric films were obtained from 36 Kuwaiti females and 32 Kuwaiti males
      between the ages 11 and 14 years. Only subjects with Class I molar occlusion and
      a positive overjet of no more than 4 mm were selected. Each subject was age
      matched with White cephalometric values. Intraexaminer error, paired, and two
      sample t-tests were made. The results show that there were significant
      differences between the Kuwaiti population and the Caucasian population for the
      majority of the variables tested (P < .01). Sex produced no significant effect on
      any of the variables studied. The Kuwaiti population has fuller lips, more facial
      convexity, greater dental protrusion, a more retruded and smaller mandible, and
      shorter posterior face height than the Caucasian population.

PMID- 16637720
TI  - Dental esthetic self-perception in young adults with and without previous
      orthodontic treatment.
AB  - The aim of this study was to determine which dental esthetic self-perception
      evaluation tool discriminated better between orthodontically treated or untreated
      Peruvian young adults. A total of 630 students were randomly chosen from the 2000
      admitted in 2002 to a private university in Peru. Students undergoing active
      orthodontic treatment at the time of examination were excluded. Self-perceived
      dental esthetic appearance was evaluated through Standardized Continuum of
      Aesthetic Need, Oral Aesthetic Subjective Index Scale, and Visual Analogue Scale
      (VAS). A stepwise multivariate discriminant analysis was developed to classify
      orthodontic treatment according to the three evaluation tools. A total of 199
      students (31.6%) reported a history of orthodontic treatment. Differences between
      orthodontically treated and untreated groups were found only for the mean VAS
      score (P < .001). Although three different approaches were used to evaluate
      dental esthetic self-perception, only VAS allowed the discrimination of the self
      perceived dental appearance between orthodontically treated and untreated
      Peruvian university young adults. Similarities in the self-perceived dental
      appearance of treated and untreated groups reported in previous epidemiological
      studies could be explained because different evaluation instruments were used.
      Further studies are required to support current findings.

PMID- 16637721
TI  - Orthodontic treatment need in Peruvian young adults evaluated through dental
      aesthetic index.
AB  - The objectives of this study were to evaluate the frequency and severity of the
      malocclusion and treatment needs in Peruvian young adults. The second aim was to
      compare the orthodontic treatment needs according to sex and socio-economic
      status (SES). This cross-sectional study was conducted at the University Dental
      Clinic of a private university in Lima, Peru. A total of 267 freshmen (from 16 to
      25 years old) were randomly selected from a pool of 780 students. Students
      wearing an orthodontic appliance or reporting a history of orthodontic treatment
      were excluded from the study. Clinical examinations were conducted using the
      Dental Aesthetic Index (DAI). Mann-Whitney and Kruskal-Wallis tests were used to
      compare the DAI scores according to sex and SES, respectively. The mean DAI score
      was 28.87 points (IC(95%) 27.77; 29.97, where IC indicates interval of
      confidence). Around one-third of the sample presented severe or very severe
      malocclusion, which implies a highly desirable or mandatory orthodontic treatment
      need. No statistically significant difference was found between the DAI scores
      according to sex (P = .592) and SES (P = .397). Approximately one-third of the
      evaluated Peruvian young adults would need orthodontic treatment according to the
      DAI. In this population, malocclusion was characterized by a relatively high
      frequency of missing teeth, appreciable dental crowding, and inadequate
      anteroposterior relationships.

PMID- 16637722
TI  - Factors affecting patient satisfaction after orthodontic treatment.
AB  - The objective of this study was to identify factors that may affect patients'
      satisfaction with their dentition after orthodontic treatment. Fifty patients (20
      males and 30 females; mean age 20.7 +/- 4.2 years) who successfully had finished
      fixed orthodontic treatment were included in the study. All subjects were treated
      with upper and lower fixed orthodontic appliances for an average duration of 19
      +/- 4 months and were in retention stage (6-12 months) with upper Hawley and
      lower fixed bonded retainers. Dental Impact on Daily Living questionnaire was
      used to assess the effect of orthodontic treatment on daily living and
      satisfaction with the dentition in the study sample. The NEO Five Factor
      inventory was used to assess personality profiles in the study sample.
      Comparisons between groups were made using chi-square test. Personality traits
      were found to be correlated with patients' satisfaction with their dentition
      after orthodontic treatment. Higher neuroticism scores had a significant negative
      relationship with total satisfaction with the dentition (P < .05). Age, sex, and
      pretreatment orthodontic treatment need had no relationship with the patient's
      satisfaction. Patients treated nonextraction showed more dissatisfaction with
      their dentition (P < .05). In orthodontically treated patients, higher
      neuroticism scores were associated with lower levels of satisfaction with the
      dentition.

PMID- 16637723
TI  - Long-term dentofacial changes in Chinese obstructive sleep apnea patients after
      treatment with a mandibular advancement device.
AB  - The objective of this study was to evaluate long-term dentofacial changes in
      Chinese obstructive sleep apnea (OSA) patients treated with a mandibular
      advancement device (MAD). Lateral cephalograms in natural head posture were
      obtained from 67 consecutive OSA patients (mean age = 46.9 +/- 8.9 years) treated
      with an MAD. The cephalograms were obtained at start of treatment (T0), after 1
      year (T1), 2 years (T2), and 3 years (T3) of treatment. The lateral cephalograms
      were digitized twice, and the average of two readings was used for statistical
      analyses. Small, but statistically significant changes occurred in some
      dentofacial variables. The lower anterior facial height steadily increased during
      the observation period, and this increase was significant for the T0-T1 and T1-T2
      periods and marginally significant for the T2-T3 period. A significant increase
      in the mandibular plane angle was observed during the T0-T1 and T2-T3 periods
      only. Significant reductions in the overjet and overbite were observed for the T0
      T1 period but not thereafter. Statistically significant dentofacial changes were
      observed in this study, but they were of small magnitude. The overjet and
      overbite changes observed mainly occurred at the initial stage of treatment.

PMID- 16637724
TI  - Dental arch diameters and relationships to oral habits.
AB  - The objective was to analyze variations in dental arch width in relation to oral
      habits. Maxillary and mandibular intercanine and intermolar distance were
      determined in relation to certain oral habits in 1297 children (ages 3 to 6
      years). After an oral examination, the parents of each child completed a
      questionnaire about oral habits, including the use of a dummy or a bottle (or
      both), finger sucking, mouth breathing, breast- or bottle-feeding, and duration
      of these habits. Data were subjected to statistical analysis by the chi-square
      test for qualitative variables and analysis of variance for quantitative
      variables with homogeneous variances. Statistical significance was P < .05. In
      general, the maxillary arch was larger than the mandibular arch with regard to
      both the intercanine and the intermolar distances and more significantly so in
      boys. In relation to age, a significant increase was found only for the
      mandibular intercanine distance (P = .001). When arch width was analyzed in
      relation to various oral habits, the maxillary intercanine distance was less in
      children who used a dummy, especially one of a round design (P = .003). The
      maxillary intercanine distance was also less in children who breathed through
      their mouth (P = .002). In most cases, dummy use and mouth breathing were
      associated with a reduction in the intercanine distance in the maxillary arch. A
      dummy habit leads to a reduction in maxillary arch width, and mouth breathing
      causes a reduction in the size of both arches.

PMID- 16637725
TI  - Dental arch dimensions in the mixed dentition: a study of Italian children born
      in the 1950s and the 1990s.
AB  - The objective of this study was to compare the dental arch dimensions in the
      mixed dentition in two modern samples living in the same geographic area and
      separated by almost 35 years. A group of 83 subjects (39 boys and 44 girls) born
      between 1953 and 1959 (mean age: eight years and three months +/-15 months for
      the boys and seven years and 11 months +/-12 months for the girls) were compared
      with a group of 84 subjects (38 boys and 46 girls) born between 1990 and 1998
      (mean age: eight years and eight months +/-12 months for the boys and eight years
      and four months +/-11 months for the girls). Measurements were taken on dental
      casts for posterior and anterior arch segments, intermolar and intercanine width,
      and mesiodistal size of incisors. The available anterior space in both arches and
      the posterior and anterior transverse dimensions were calculated. Groups were
      compared using a nonparametric test (Mann-Whitney U-test) for independent samples
      (P < .05). Results show that both boys and girls of 1990s showed significantly
      smaller maxillary intermolar width when compared with 1950s. Posterior transverse
      interarch discrepancy was significantly minor in girls of 1990s. The present
      population has a greater probability of developing a malocclusion as a
      consequence of the secular trend toward the reduction of the width of the upper
      arch.

PMID- 16637726
TI  - Functional relationships between the masseter and sternocleidomastoid muscle
      activities during gum chewing:.
AB  - The purpose of this study was to investigate the functional relationship between
      masseter muscle (MM) and sternocleidomastoid muscle (SCM) activities and between
      mandibular and head movements during mastication, under experimental muscle
      fatigue. The sample consisted of 12 adults with individually normal occlusion.
      The subjects were asked to chew gum at three different times: before maximum
      clenching, immediately after maximum clenching, and 3 minutes after maximum
      clenching. At these times, we examined the activity of the MM and SCM as well as
      the movement of the mandible and head. The activity and movement were
      simultaneously measured using both electromyography and the motion capture
      system. The MM activity time after clenching was significantly shorter than that
      before clenching, whereas the SCM activity time was significantly longer after
      clenching. There was no significant difference in the changes of three
      dimensional distance of the mandibular movement between the respective times. On
      the other hand, the changes in the three-dimensional distance of head movement
      after clenching increased when compared with before clenching. Furthermore, the
      difference in the time of MM and SCM activity onset and of mandibular and head
      movement onset after clenching was shorter than that before clenching. A
      functional relationship exists between the MM and SCM activities and between
      mandibular and head movements during mastication.

PMID- 16637727
TI  - Tooth size discrepancies and arch parameters among different malocclusions in a
      Jordanian sample.
AB  - The objectives of this study were to determine the mean mesiodistal tooth width
      of the dentition, Bolton anterior and overall ratios, arch length, and arch width
      in the different malocclusions in a Jordanian sample. The mesiodistal tooth
      width, arch width, and length were measured on a total of 140 orthodontic models
      of school students aged 13-15 years of different occlusal relationships (Class I,
      Class II division 1, Class II division 2, and Class III malocclusions). Anterior
      and overall Bolton ratios were calculated. The mean and standard deviation were
      calculated. Student's t-test and analysis of variance were used for the
      statistical analysis. The results show that (1) females have smaller teeth than
      males; (2) Class III malocclusion showed larger teeth than the rest of the other
      occlusal categories; (3) no statistically significant differences were found in
      Bolton ratios between the different malocclusions; (4) Class II division 1 showed
      the narrowest maxillary arch compared with the other types of malocclusion; (5)
      the mandibular intercanine width was significantly larger in Class III group than
      in Class II division 1 and Class II division 2 groups; (6) the maxillary arch was
      significantly longer in Class II division 1 than in Class II division 2; and (7)
      the mandibular arch of both Class II categories was significantly shorter than
      Class III malocclusion group. In conclusion, tooth size differences were found
      between right and left sides, between females and males, and between the
      different malocclusions. Arch width and length also showed differences among the
      different malocclusions.

PMID- 16637728
TI  - Evaluation of a new self-etching primer on bracket bond strength in vitro.
AB  - The purpose of this in vitro study was to evaluate the influence of a new self
      etching primer (Adper Prompt L-pop; 3M ESPE, St Paul, Minn) on shear bond
      strength of orthodontic brackets. Forty extracted human premolars were obtained
      and randomly divided into two groups of 20 each: group 1 (control), phosphoric
      acid + Transbond XT primer (3M Unitek, Monrovia, Calif) and group 2, Adper Prompt
      L-pop. Transbond XT adhesive paste (3M Unitek) was used in both groups for
      bracket bonding. All products were used according to the manufacturer's
      instructions. Instron Universal Testing Machine was used to apply an occlusal
      shear force directly onto the enamel-bracket interface at a speed of 0.5 mm/min.
      The groups were compared using Student's t-test. Mean results and standard
      deviation for the groups were: group 1 = 16.23 MPa (4.77), group 2 = 13.56 MPa
      (4.31). No significant difference was observed in the bond strengths of the two
      groups evaluated (P = .069). However, the adhesive remnant index was
      significantly less when conditioning the enamel with Adper Prompt L-pop compared
      with phosphoric acid (P = .0003). The results suggest no difference in bond
      strength whether a conventional etching and primer or Adper Prompt L-pop is used.
      The amount of adhesive on the enamel after debonding was significantly less when
      using Adper Prompt than when using phosphoric acid. These results indicated that
      Adper Prompt is potentially adequate for orthodontic bonding needs.

PMID- 16637729
TI  - Shear bond strength of resin-modified glass ionomer cement with saliva present
      and different enamel pretreatments.
AB  - The purpose of this study was to evaluate the shear bond strength of resin
      modified glass ionomer cement in a saliva-contaminated environment, using
      different enamel pretreatments. A total of 125 freshly extracted, bovine
      permanent inferior incisors were divided into five groups. Group I received 10%
      polyacrylic acid, moistened with saliva/Fuji Ortho LC (FOLC); group II received
      37% phosphoric acid, moistened with saliva/FOLC; group III was moistened with
      saliva/ FOLC, without acid etching; group IV received 10% polyacrylic acid, not
      moistened with saliva/ FOLC; and group V was used as a control with 37%
      phosphoric acid/dry/Transbond XT. After the bonding procedures, all samples were
      thermocycled, tested in a shear mode on a testing machine, and the Adhesive
      Remnant Index was evaluated. One-way analysis of variance and Tukey's honestly
      significant difference (HSD) tests indicated that group V yielded the highest
      shear bond strength (4.09 MPa) but with no statistically significant difference
      from group II (3.88 MPa). There were no statistically significant differences
      between groups I, III, and IV (2.84, 2.90, and 3.22 MPa, respectively) (P > or =
      .05). In groups I, II, IV, and V, where enamel was etched, more than 50% of the
      samples showed that all material adhered to the teeth surfaces. This was opposed
      to group III, where the bond failure was mostly between the enamel interface and
      the bonding material. The results indicated that in a saliva-moistened
      environment, FOLC achieved higher shear bond strength when 37% phosphoric acid is
      used, with no statistically significant difference from Transbond XT.

PMID- 16637730
TI  - Orthodontic latex elastics: a force relaxation study.
AB  - The objectives of this study were to assess the force relaxation of latex
      elastics occurring within 24 hours of extension and to estimate the extension
      required to reach the reported force. Five specimens of various manufacturers'
      latex elastics size and force levels were mounted on a custom-made setup capable
      of monitoring force levels in real time with a continuous mode and without
      operator intervention. The percentage of force relaxation was estimated from the
      initial and 24-hour levels, and the results were analyzed with one-way analysis
      of variance and the Tukey test at alpha = 0.05 level of significance. The
      elastics showed force relaxation in the order of 25%, which consisted of an
      initial high slope component and a latent part of decreased rate. Most relaxation
      occurred within the first 3-5 hours after extension, regardless of size,
      manufacturer, or force level of the elastic. The overall as well as the initial
      relaxation curves were fitted to equations, which described the variation of
      force with time. Elastic extension to achieve the reported force was found to
      range between 2.7 and five times the original length. Latex elastics show force
      relaxation in the order of 25%, which consists of an initial high slope component
      and a latent part of decreased rate. Most relaxation occurs within the first 3-5
      hours after extension, regardless of size, manufacturer, or force level of the
      elastic. The empirical rule of "3" shows remarkable variation, ranging from 2.7
      to five.

PMID- 16637731
TI  - A clinical trial of Damon 2 vs conventional twin brackets during initial
      alignment.
AB  - The objective of this study was to compare the effectiveness and comfort of Damon
      2 brackets and conventional twin brackets during initial alignment. Sixty
      consecutive patients participated in a split mouth design. One side of the lower
      arch was bonded with the Damon 2 bracket and the other with a conventional twin
      bracket. The sides were alternated with each consecutive patient. The
      irregularity index (II) was measured for each half of the arch at baseline, at 10
      weeks at the first archwire change, and at another 10 weeks at the second
      archwire change. Any difference in discomfort was assessed within the first few
      days of archwire placement and again at the first archwire change. Comfort on the
      lips, preferred look, and bracket failure rates were also recorded. The twin
      bracket was more uncomfortable with the initial archwire (P = .04). However, at
      10 weeks, substantially more patients reported discomfort with the Damon 2
      bracket when engaging the archwire (P = .004). At both archwire changes at 10 and
      20 weeks (P = .001), the conventional bracket had achieved a lower II than the
      Damon 2 bracket by 0.2 mm, which is not clinically significant. Patients
      preferred the look of the twin bracket over the Damon 2 (P < .0005) and more
      Damon 2 brackets debonded during the study (P < .0005). The Damon 2 bracket was
      no better during initial alignment than a conventional bracket. Initially, the
      Damon 2 bracket was less painful, but it was substantially more painful when
      placing the second archwire and had a higher bracket failure rate.

PMID- 16637732
TI  - Platelet-derived growth factor enhances proliferation and matrix synthesis of
      temporomandibular joint disc-derived cells.
AB  - Platelet-derived growth factor (PDGF) is an essential signaling molecule for
      wound healing and tissue repair. This study was aimed at evaluating the effect of
      PDGF on the proliferation of temporomandibular joint (TMJ) disc-derived cells and
      extracellular matrix synthesis. The number of cultured cells were counted by
      COULTER Z1. The assay for collagen synthesis was performed using a sircol soluble
      collagen assay. Hyaluronic acid (HA) synthesis was analyzed by a high performance
      liquid chromatography. The expression of collagens, matrix metalloproteinases
      (MMPs), and the tissue inhibitors of metalloproteinases (TIMPs) were examined
      using SYBR Green in terms of the RNA levels. PDGF treatment significantly (P <
      .01) increased the proliferation rate of the disc-derived cells as compared with
      the controls when the dose was 5 ng/ mL or greater. Treatment with more than 5
      ng/mL PDGF resulted in an amount of collagen synthesis significantly (P < .01)
      higher than the controls. HA synthesis was maximal with 5 ng/mL PDGF treatment.
      Quantitative real-time polymerase chain reaction analyses showed that treatment
      with 5 ng/mL of PDGF-BB upregulated the mitochondrial RNA levels of type I and II
      collagens, MMPs, and TIMPs within 6 hours. It is concluded that PDGF, if its
      concentration is optimal, enhanced proliferation and matrix synthesis of TMJ disc
      derived cells, indicating that PDGF may be effective for use in tissue
      engineering of the TMJ disc.

PMID- 16637733
TI  - Orthodontic anchorage: a systematic review.
AB  - The aim of this systematic review was to examine, in an evidence-based way, what
      kind of orthodontic anchorage systems/applications are evaluated and their
      effectiveness. A literature survey from the Pub Med and Cochrane databases
      covering the period from January 1966 to December 2004 was performed. Randomized
      controlled trials (RCT), prospective and retrospective controlled studies, and
      clinical trials comparing at least two anchorage situations were included. Two
      reviewers selected and extracted the data independently and also assessed the
      quality of the retrieved studies. The search strategy resulted in 494 articles,
      of which 14 met the inclusion criteria. Two main anchorage situations were
      identified: anchorage of molars during space closure after premolar extractions
      and anchorage loss in the incisor or premolar region (or both) during molar
      distalization. Because of contradictory results and the vast heterogeneity in
      study methods, the scientific evidence was too weak to evaluate anchorage
      efficiency during space closure. Intraoral molar distalization leads to anchorage
      loss in various amounts depending on the choice of distalization unit. Most of
      the studies had serious problems with small sample size, confounding factors,
      lack of method error analysis, and no blinding in measurements. To obtain
      reliable scientific evidence, controlled RCT's with sufficient sample sizes are
      needed to determine which anchorage system is the most effective in the
      respective anchorage situation. Further studies should also consider patient
      acceptance and cost analysis as well as implants as anchorage.

PMID- 16637734
TI  - Unilateral horizontally impacted maxillary canine and first premolar treated with
      a double archwire technique.
AB  - A patient with a unilateral horizontally impacted upper left canine and first
      premolar was treated orthodontically. The use of a double archwire technique
      achieved the desired treatment goals. We discuss the problems associated with
      impacted maxillary canines and first premolars and the biomechanical
      interventions used for this patient.

PMID- 16637735
TI  - Severe crowding and a dilacerated maxillary central incisor in an adolescent.
AB  - This study reports the treatment of an adolescent patient with dilacerated
      maxillary incisor. She complained of severe crowding with a high-positioned left
      upper canine. Her left central incisor had been impacted and moved to proper
      position at the age of eight years, resulting in a severe root dilaceration. To
      avoid any progression of root dilacerations and resorption in the maxillary
      incisor, maxillary lateral expansion and molar distalization plus multibracket
      appliance were selected as the best nonextraction treatment plan. The maxillary
      expansion and molar distalization should provide adequate space for the
      correction of the severe crowding, and treatment with a multibracket appliance
      was initiated. After a 17-month treatment with a multibracket appliance, an
      acceptable occlusion was achieved with a Class I molar relationship. An
      acceptable occlusion was maintained without recurrence of the crowding and
      impairment of the dilacerated root in the maxillary incisor during three years of
      retention. It is emphasized that careful planning is required to avoid any
      progression of the root dilaceration and resorption through orthodontic
      treatment. A shortening of the period of applying orthodontic force on the
      dilacerated incisor and avoidance of tooth extraction will minimize the risk
      factors.

PMID- 16637736
TI  - New generation open-bite treatment with zygomatic anchorage.
AB  - This technical note aims to present the fabrication and application of a new
      generation of posterior intrusion appliances using zygomatic anchorage. The use
      of zygomatic anchorage enables en masse impaction of the posterior segment
      without any side effects such as labial flaring. A 14-year-old, female Class II
      patient with an anterior open bite was treated with a new generation posterior
      intrusion appliance. At the end of treatment, a Class I canine and molar
      relationship and a correction of the anterior open bite were achieved. The molars
      were impacted 3.6 mm, and this impaction was maintained throughout the treatment.
      The mandibular plane showed a counterclockwise autorotation of 4 degrees. This
      case report demonstrates that zygomatic anchorage can be used effectively for
      molar intrusion and anchorage maintenance. However, further clinical studies with
      larger samples are required to confirm its effectiveness.

PMID- 16637737
TI  - Nonsurgical correction of an adult skeletal class III and open-bite malocclusion.
AB  - This case report presents an adult skeletal Class III and open-bite malocclusion
      case treated without surgical intervention using fixed edgewise technique,
      reverse headgear, and Class III and anterior box elastics. The patient was a 16
      year-old Turkish female who had completed her growth and development. She had a
      four mm open bite, maxillary retrognathia, a crossbite in the anterior and left
      posterior, and hypoplasia of the maxillary laterals. In addition, the patient's
      first molars had previously been extracted because of caries, and extraction
      spaces were present. We applied a Roth edgewise appliance and a reverse headgear
      to be used at night only for the first six months. The objective in using a
      reverse headgear was to displace the maxillary teeth toward the mesial and to
      rotate the maxilla in a clockwise direction. In the mandible, we retracted the
      mandibular incisors and canine teeth and moved the second molars mesially toward
      the first molar extraction space. There would thus be no need for any prosthetic
      restoration in the mandible. At the end of treatment, we obtained a Class I
      dental relationship, an ideal occlusion relationship, and an esthetic dental and
      facial relationship. Treatment of the patient was completed in 20 months.

PMID- 16637738
TI  - Mental paresthesia and orthodontic treatment.
AB  - This article reports a case of mental paresthesia during orthodontic treatment.
      It also discusses which cases may be at risk for developing mental paresthesia
      and its prevention and management.

PMID- 16637739
TI  - The medical model in orthodontic education.

PMID- 16637741
TI  - Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2
      genotype.
AB  - BACKGROUND: Anaemia is a major cause of morbidity and mortality for children in
      Africa. The plasma protein haptoglobin (Hp) binds avidly to free haemoglobin
      released following malaria-induced haemolysis. Haptoglobin polymorphisms result
      in proteins with altered haemoglobin-binding capacity and different antioxidant,
      iron-recycling, and immune functions. Previous studies examined the importance of
      haptoglobin polymorphism in malaria and iron homeostasis, but it is unknown
      whether haptoglobin genotype might be a risk factor for anaemia in children in a
      malaria-endemic area. METHODS AND FINDINGS: A cohort of 780 rural Gambian
      children aged 2-6 y was surveyed at the start and end of the malaria season.
      Samples were taken to assess haemoglobin (Hb) concentration, iron status
      (ferritin, zinc protoporphyrin, transferrin saturation, and soluble transferrin
      receptor concentration), haptoglobin concentration, alpha-1-antichymotrypsin (a
      measure of inflammation), and malaria parasites on blood film. We extracted DNA
      and genotyped for haptoglobin, sickle cell, and glucose-6-phosphate (G6PD)
      deficiency. Mean Hb levels fell over the malaria season. Children with the
      haptoglobin 2-2 genotype (17%) had a greater mean drop in Hb level over the
      malaria season (an 8.9 g/l drop; confidence interval [CI] 5.7, 12.1) compared to
      other children (a 5.1 g/l drop; CI 3.8, 6.4). In multivariate regression
      analysis, controlling for baseline Hb level, age group, village, malaria
      parasites on blood film, iron status, haptoglobin concentration, and G6PD
      deficiency, haptoglobin genotype predicted Hb level at the end of the malaria
      season (p = 0.0009, coefficient = -4.2). Iron status was not influenced by
      haptoglobin genotype. CONCLUSIONS: The finding that haptoglobin 2-2 genotype is a
      risk factor for anaemia in children in a malaria-endemic area may reflect the
      reduced ability of the Hp2-2 polymer to scavenge free haemoglobin-iron following
      malaria-induced haemolysis. The magnitude of the effect of haptoglobin genotype
      (4 g/l Hb difference, p = 0.0009) was comparable to that of G6PD deficiency or
      HbAS (3 g/l difference, p = 0.03; and 2 g/l difference, p = 0.68, respectively).

PMID- 16637742
TI  - Differential effects of HOXB4 on nonhuman primate short- and long-term
      repopulating cells.
AB  - BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to
      self-renew and differentiate into cells of all hematopoietic lineages, and they
      can be enriched using the CD34 cell surface marker. Because of this unique
      property, HSCs have been used for HSC transplantation and gene therapy
      applications. However, the inability to expand HSCs has been a significant
      limitation for clinical applications. Here we examine, in a clinically relevant
      nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially
      overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation
      assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green
      fluorescent protein) and control (yellow fluorescent protein [YFP])-transduced
      and expanded CD34+ cells. In three animals, cells were infused after a 3-d
      transduction culture, while in three other animals cells were infused after an
      additional 6-9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression
      resulted in superior engraftment in all animals. The most dramatic effect of
      HOXB4 was observed early after transplantation, resulting in an up to 56-fold
      higher engraftment compared to the control cells. At 6 mo after transplantation,
      the proportion of marker gene-expressing cells in peripheral blood was still up
      to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS:
      These data demonstrate that HOXB4 overexpression in CD34+ cells has a dramatic
      effect on expansion and engraftment of short-term repopulating cells and a
      significant, but less pronounced, effect on long-term repopulating cells. These
      data should have important implications for the expansion and transplantation of
      HSCs, in particular for cord blood transplantations where often only suboptimal
      numbers of HSCs are available.

PMID- 16637743
TI  - What is the relationship between haptoglobin, malaria, and anaemia?

PMID- 16637744
TI  - Advertising in medical journals: should current practices change?

PMID- 16637745
TI  - Embodied temporal perception of emotion.
AB  - The role of embodiment in the perception of the duration of emotional stimuli was
      investigated with a temporal bisection task. Previous research has shown that
      individuals overestimate the duration of emotional, compared with neutral, faces
      (S. Droit-Volet, S. Brunot, & P. M. Niedenthal, 2004). The authors tested a role
      for embodiment in this effect. Participants estimated the duration of angry,
      happy, and neutral faces by comparing them to 2 durations learned during a
      training phase. Experimental participants held a pen in their mouths so as to
      inhibit imitation of the faces, whereas control participants could imitate
      freely. Results revealed that participants overestimated the duration of
      emotional faces relative to the neutral faces only when imitation was possible.
      Implications for the role of embodiment in emotional perception are discussed.

PMID- 16637746
TI  - Awareness of faces is modulated by their emotional meaning.
AB  - A central question in perception is how stimuli are selected for access to
      awareness. This study investigated the impact of emotional meaning on detection
      of faces using the attention blink paradigm. Experiment 1 showed that fearful
      faces were detected more frequently than neutral faces, and Experiment 2 revealed
      preferential detection of fearful faces compared with happy faces. To rule out
      image artifacts as a cause for these results, Experiment 3 manipulated the
      emotional meaning of neutral faces through fear conditioning and showed a
      selective increase in detection of conditioned faces. These results extend
      previous reports of preferential detection of emotional words or schematic
      objects and suggest that fear conditioning can modulate detection of formerly
      neutral stimuli.

PMID- 16637747
TI  - From fear to love: individual differences in implicit spider associations.
AB  - The Implicit Association Test (IAT) was used to investigate automatic fear
      associations in fear of spiders. Fear associations toward spiders were measured
      among spider fearful and nonfearful participants (Experiment 1) as well as among
      nonfearfuls and spider enthusiasts (Experiment 2). It was shown that the IAT is
      sensitive to personal automatic fear associations and therefore distinguishes
      between high-fearful, nonfearful, and enthusiastic participants. Moreover,
      implicit spider associations measured by the IAT predicted avoidance behavior
      beyond self-reports. The results of Experiment 2 provide additional support for
      the argument that implicit spider associations are different from general
      stereotypes or knowledge about spiders.

PMID- 16637748
TI  - Flanker effects with faces may depend on perceptual as well as emotional
      differences.
AB  - Do threatening or negative faces capture attention? The authors argue that
      evidence from visual search, spatial cuing, and flanker tasks is equivocal and
      that perceptual differences may account for effects attributed to emotional
      categories. Empirically, the authors examine the flanker task. Although they
      replicate previous results in which a positive face flanked by negative faces
      suffers more interference than a negative face flanked by positive faces, further
      results indicate that face perception is not necessary for the flanker-effect
      asymmetry and that the asymmetry also occurs with nonemotional stimuli. The
      authors conclude that the flanker-effect asymmetry with affective faces cannot be
      unambiguously attributed to emotional differences and may well be due to purely
      perceptual differences between the stimuli.

PMID- 16637749
TI  - Anxiety selectively disrupts visuospatial working memory.
AB  - On the basis of a review of the extant literature describing emotion-cognition
      interactions, the authors propose 4 methodological desiderata for studying how
      task-irrelevant affect modulates cognition and present data from an experiment
      satisfying them. Consistent with accounts of the hemispheric asymmetries
      characterizing withdrawal-related negative affect and visuospatial working memory
      (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively
      disrupted accuracy of spatial but not verbal WM performance. Furthermore,
      individual differences in physiological measures of anxiety statistically
      mediated the degree of disruption. A second experiment revealed that individuals
      characterized by high levels of behavioral inhibition exhibited more intense
      anxiety and relatively worse spatial WM performance in the absence of threat,
      solidifying the authors' inference that anxiety causally mediates disruption.
      These observations suggest a revision of extant models of how anxiety sculpts
      cognition and underscore the utility of the desiderata.

PMID- 16637750
TI  - Lexical characteristics of words used in emotional Stroop experiments.
AB  - Validity of the emotional Stroop task hinges on equivalence between the emotion
      and the control words in terms of lexical features related to word recognition.
      The authors evaluated the lexical features of 1,033 words used in 32 published
      emotional Stroop studies. Emotion words were significantly lower in frequency of
      use, longer in length, and had smaller orthographic neighborhoods than words used
      as controls. These lexical features contribute to slower word recognition and
      hence are likely to contribute to delayed latencies in color naming. The often
      replicated slowdown in color naming of emotion words may be due, in part, to
      lexical differences between the emotion and control words used in the majority of
      such studies to date.

PMID- 16637751
TI  - Amygdalectomy and responsiveness to novelty in rhesus monkeys (Macaca mulatta):
      generality and individual consistency of effects.
AB  - Rhesus monkeys (Macaca mulatta) with bilateral ibotenic acid-produced lesions of
      the amygdala were compared with controls in several novel situations, including
      exposures to metal objects, toy animals, and a person. Early in testing, the
      monkeys with lesions showed reduced inhibitions on responsiveness compared with
      controls. With continuing exposures, differences between groups diminished
      sharply as inhibitions waned in the controls. This outcome is consistent with the
      hypothesis that the amygdala mediates caution in initial reactions to ambiguous
      or threatening novel situations, which, in the absence of adverse consequences,
      diminishes with repetition. Consistency of individual responsiveness across
      different situations, including pairing with other monkeys, was substantial in
      lesioned and normal monkeys, suggesting that stable qualities of temperament
      influenced the results in both groups.

PMID- 16637752
TI  - Limits of symhedonia: the differential role of prior emotional attachment in
      sympathy and sympathetic joy.
AB  - Seven studies tested the hypothesis that compared with sympathy symhedonia
      (sympathy for another's good fortune) is inherently more contingent on prior
      emotional attachment to its targets. As predicted, Studies 1-4 found that
      reported attachment was higher for past episodes of symhedonia than for those of
      sympathy and that recalled incidence of sympathy exceeded that of symhedonia when
      the target was a stranger. Study 5 showed that whereas symhedonia was
      significantly higher for high- versus low-attachment targets sympathy was not.
      Study 6 found that sympathy is more likely than symhedonia when a relationship is
      strained. Study 7 found that both sympathy and symhedonia are weaker for nonclose
      (vs. close) others, but the disparity is significantly smaller for sympathy than
      for symhedonia.

PMID- 16637753
TI  - Anxiety meets fear in perception of dynamic expressive gaze.
AB  - This study investigated in 2 experiments whether reflexive cuing of attention
      that occurs after perception of a gaze cue is greater for fearful than for happy
      faces in normal participants, as hypothesized from a social neuroscience
      perspective. To increase neuroecological validity, dynamic stimulus presentation
      was used to display faces that simultaneously morphed from a neutral expression
      into a happy or fearful one and shifted eye gaze from the center to the
      periphery. Shifts of attention resulting from a natural fearful gaze were
      expected to be related to participants' anxiety traits, in agreement with the
      often found increased selective attention to threat in anxious participants. Both
      hypotheses were confirmed: Fearful faces induced stronger gaze cuing than happy
      faces, and the strength of this cuing effect was correlated to participants'
      anxiety levels. These results suggest a neural network, which integrates the
      processing of gaze, expression, and emotional states to adaptively prime
      vigilance under threatening circumstances.

PMID- 16637754
TI  - Culture, ethnicity, and children's facial expressions: a study of European
      American, Mainland Chinese, Chinese American, and adopted Chinese girls.
AB  - This investigation extends previous research documenting differences in Chinese
      and European American infants' facial expressivity. Chinese girls adopted by
      European American families, nonadopted Mainland Chinese girls, nonadopted Chinese
      American girls, and nonadopted European American girls responded to emotionally
      evocative slides and an odor stimulus. European American girls smiled more than
      Mainland Chinese and Chinese American girls and scored higher than Mainland
      Chinese girls for disgust-related expressions and overall expressivity. Adopted
      Chinese girls produced more disgust-related expressions than Mainland Chinese
      girls. Self-reported maternal strictness, aggravation, positive expressiveness,
      and cultural identification correlated with children's facial responses, as did
      number of siblings and adults in the home. Results suggest that culture and
      family environment influences facial expressivity, creating differences among
      children of the same ethnicity.

PMID- 16637755
TI  - Gender differences in the negative affective priming of aggressive behavior.
AB  - The negative affective priming of aggression was examined across different
      aversive contexts (general stress exposure and frustration) with a laboratory
      aggression paradigm that measured the intensity of shocks participants delivered
      to a putative employee. Participants' emotional responses were gauged via startle
      eyeblink reactions and self-report mood ratings. Aside from gender differences in
      overall aggression, men but not women exposed to general stress showed
      significant increases in aggression across blocks. However, frustration produced
      increases in aggression in both genders. Although both genders showed robust
      startle increases during stress, startle activation was related to increases in
      aggression in men and decreases in aggression in women. These findings suggest
      that general stress and experiences of negative emotion trigger physical
      aggressive responses more strongly in men than in women.

PMID- 16637756
TI  - Language and the perception of emotion.
AB  - Three studies assessed the relationship between language and the perception of
      emotion. The authors predicted and found that the accessibility of emotion words
      influenced participants' speed or accuracy in perceiving facial behaviors
      depicting emotion. Specifically, emotion words were either primed or temporarily
      made less accessible using a semantic satiation procedure. In Studies 1 and 2,
      participants were slower to categorize facial behaviors depicting emotion (i.e.,
      a face depicting anger) after an emotion word (e.g., "anger") was satiated. In
      Study 3, participants were less accurate to categorize facial behaviors depicting
      emotion after an emotion word was satiated. The implications of these findings
      for a linguistically relative view of emotion perception are discussed.

PMID- 16637757
TI  - A population approach to the study of emotion: diurnal rhythms of a working day
      examined with the Day Reconstruction Method.
AB  - To date, diurnal rhythms of emotions have been studied with real-time data
      collection methods mostly in relatively small samples. The Day Reconstruction
      Method (DRM), a new survey instrument that reconstructs the emotions of a day, is
      examined as a method for enabling large-scale investigations of rhythms. Diurnal
      cycles were observed for 12 emotion adjectives in 909 women over a working day.
      Bimodal patterns with peaks at noon and evenings were detected for positive
      emotions; peaks in negative emotions were found at mid-morning and mid-afternoon.
      A V-shaped pattern was found for tired and an inverted U-shaped pattern for
      competent. Several diurnal patterns from prior studies were replicated. The DRM
      appears to be a useful tool for the study of emotions.

PMID- 16637758
TI  - Differential subjective and psychophysiological responses to socially and
      nonsocially generated emotional stimuli.
AB  - Sociality may determine the subjective experience and physiological response to
      emotional stimuli. Film segments induced socially and nonsocially generated
      emotions. Comedy (social positive), bereavement (social negative), pizza scenes
      (nonsocial positive), and wounded bodies (nonsocial negative) elicited four
      distinct emotional patterns. Per subjective report, joy, sadness, appetite, and
      disgust were elicited by the targeted stimulus condition. The social/nonsocial
      dimension influenced which emotional valence(s) elicited a skin conductance
      response, a finding that could not be explained by differences in subjective
      arousal. Heart rate deceleration was more responsive to nonsocially generated
      emotions. Taken together, these findings suggest that sociality affects the
      physiological profile of responses to emotional valence.

PMID- 16637759
TI  - When people fall from grace: reconsidering the role of envy in Schadenfreude.
AB  - Previous research yielded conflicting results concerning the role of envy in
      predicting Schadenfreude (pleasure at another's misfortune). Some studies showed
      that envy predicts Schadenfreude, whereas others did not. Results of the present
      research reconcile these opposing findings, by showing that envy is a predictor
      of Schadenfreude when the target is similar to the observer in terms of gender.
      These results suggest that envy predicts Schadenfreude when people are confronted
      with the misfortune of a relevant social comparison other.

PMID- 16637760
TI  - Short-term memory for serial order: a recurrent neural network model.
AB  - Despite a century of research, the mechanisms underlying short-term or working
      memory for serial order remain uncertain. Recent theoretical models have
      converged on a particular account, based on transient associations between
      independent item and context representations. In the present article, the authors
      present an alternative model, according to which sequence information is encoded
      through sustained patterns of activation within a recurrent neural network
      architecture. As demonstrated through a series of computer simulations, the model
      provides a parsimonious account for numerous benchmark characteristics of
      immediate serial recall, including data that have been considered to preclude the
      application of recurrent neural networks in this domain. Unlike most competing
      accounts, the model deals naturally with findings concerning the role of
      background knowledge in serial recall and makes contact with relevant
      neuroscientific data. Furthermore, the model gives rise to numerous testable
      predictions that differentiate it from competing theories. Taken together, the
      results presented indicate that recurrent neural networks may offer a useful
      framework for understanding short-term memory for serial order.

PMID- 16637761
TI  - Becoming syntactic.
AB  - Psycholinguistic research has shown that the influence of abstract syntactic
      knowledge on performance is shaped by particular sentences that have been
      experienced. To explore this idea, the authors applied a connectionist model of
      sentence production to the development and use of abstract syntax. The model
      makes use of (a) error-based learning to acquire and adapt sequencing mechanisms
      and (b) meaning-form mappings to derive syntactic representations. The model is
      able to account for most of what is known about structural priming in adult
      speakers, as well as key findings in preferential looking and elicited production
      studies of language acquisition. The model suggests how abstract knowledge and
      concrete experience are balanced in the development and use of syntax.

PMID- 16637762
TI  - Using dynamic field theory to rethink infant habituation.
AB  - Much of what psychologists know about infant perception and cognition is based on
      habituation, but the process itself is still poorly understood. Here the authors
      offer a dynamic field model of infant visual habituation, which simulates the
      known features of habituation, including familiarity and novelty effects,
      stimulus intensity effects, and age and individual differences. The model is
      based on a general class of dynamic (time-based) models that integrate
      environmental input in varying metric dimensions to reach a single decision. Here
      the authors provide simulated visual input of varying strengths, distances, and
      durations to 2 coupled and interacting fields. The 1st represents the activation
      that drives "looking," and the 2nd, the inhibition that leads to "looking away,"
      or habituation. By varying the parameters of the field, the authors simulate the
      time course of habituation trials and show how these dynamics can lead to
      different depths of habituation, which then determine how the system
      dishabituates. The authors use the model to simulate a set of influential
      experiments by R. Baillargeon (1986, 1987a, 1987b) using the well-known
      "drawbridge" paradigm. The dynamic field model provides a coherent explanation
      without invoking infant object knowledge. The authors show that small changes in
      model parameters can lead to qualitatively different outcomes. Because in typical
      infant cognition experiments, critical parameters are unknown, effects attributed
      to conceptual knowledge may be explained by the dynamics of habituation.

PMID- 16637763
TI  - Anatomy of a decision: striato-orbitofrontal interactions in reinforcement
      learning, decision making, and reversal.
AB  - The authors explore the division of labor between the basal ganglia-dopamine (BG
      DA) system and the orbitofrontal cortex (OFC) in decision making. They show that
      a primitive neural network model of the BG-DA system slowly learns to make
      decisions on the basis of the relative probability of rewards but is not as
      sensitive to (a) recency or (b) the value of specific rewards. An augmented model
      that explores BG-OFC interactions is more successful at estimating the true
      expected value of decisions and is faster at switching behavior when
      reinforcement contingencies change. In the augmented model, OFC areas exert top
      down control on the BG and premotor areas by representing reinforcement
      magnitudes in working memory. The model successfully captures patterns of
      behavior resulting from OFC damage in decision making, reversal learning, and
      devaluation paradigms and makes additional predictions for the underlying source
      of these deficits.

PMID- 16637764
TI  - The Bayesian reader: explaining word recognition as an optimal Bayesian decision
      process.
AB  - This article presents a theory of visual word recognition that assumes that, in
      the tasks of word identification, lexical decision, and semantic categorization,
      human readers behave as optimal Bayesian decision makers. This leads to the
      development of a computational model of word recognition, the Bayesian reader.
      The Bayesian reader successfully simulates some of the most significant data on
      human reading. The model accounts for the nature of the function relating word
      frequency to reaction time and identification threshold, the effects of
      neighborhood density and its interaction with frequency, and the variation in the
      pattern of neighborhood density effects seen in different experimental tasks.
      Both the general behavior of the model and the way the model predicts different
      patterns of results in different tasks follow entirely from the assumption that
      human readers approximate optimal Bayesian decision makers.

PMID- 16637765
TI  - The dynamics of perception and action.
AB  - How might one account for the organization in behavior without attributing it to
      an internal control structure? The present article develops a theoretical
      framework called behavioral dynamics that integrates an information-based
      approach to perception with a dynamical systems approach to action. For a given
      task, the agent and its environment are treated as a pair of dynamical systems
      that are coupled mechanically and informationally. Their interactions give rise
      to the behavioral dynamics, a vector field with attractors that correspond to
      stable task solutions, repellers that correspond to avoided states, and
      bifurcations that correspond to behavioral transitions. The framework is used to
      develop theories of several tasks in which a human agent interacts with the
      physical environment, including bouncing a ball on a racquet, balancing an
      object, braking a vehicle, and guiding locomotion. Stable, adaptive behavior
      emerges from the dynamics of the interaction between a structured environment and
      an agent with simple control laws, under physical and informational constraints.

PMID- 16637766
TI  - Using reinforcement learning to understand the emergence of "intelligent" eye
      movement behavior during reading.
AB  - The eye movements of skilled readers are typically very regular (K. Rayner,
      1998). This regularity may arise as a result of the perceptual, cognitive, and
      motor limitations of the reader (e.g., limited visual acuity) and the inherent
      constraints of the task (e.g., identifying the words in their correct order). To
      examine this hypothesis, reinforcement learning was used to allow an artificial
      "agent" to learn to move its eyes to read as efficiently as possible. The
      resulting patterns of simulated eye movements resembled those of skilled readers
      and suggest that important aspects of eye-movement behavior might emerge as a
      consequence of satisfying the constraints that are imposed on readers. These
      results also suggest novel interpretations of some contentious empirical results,
      such as the fixation duration costs associated with word skipping (R. Kliegl & R.
      Engbert, 2005), and theoretical assumptions, for example the familiarity check in
      the E-Z Reader model of eye-movement control (E. D. Reichle, A. Pollatsek, D. L.
      Fisher, & K. Rayner, 1998).

PMID- 16637767
TI  - The priority heuristic: making choices without trade-offs.
AB  - Bernoulli's framework of expected utility serves as a model for various
      psychological processes, including motivation, moral sense, attitudes, and
      decision making. To account for evidence at variance with expected utility, the
      authors generalize the framework of fast and frugal heuristics from inferences to
      preferences. The priority heuristic predicts (a) the Allais paradox, (b) risk
      aversion for gains if probabilities are high, (c) risk seeking for gains if
      probabilities are low (e.g., lottery tickets), (d) risk aversion for losses if
      probabilities are low (e.g., buying insurance), (e) risk seeking for losses if
      probabilities are high, (f) the certainty effect, (g) the possibility effect, and
      (h) intransitivities. The authors test how accurately the heuristic predicts
      people's choices, compared with previously proposed heuristics and 3
      modifications of expected utility theory: security-potential/aspiration theory,
      transfer-of-attention-exchange model, and cumulative prospect theory.

PMID- 16637768
TI  - Why g is not an adaptation: a comment on Kanazawa (2004).
AB  - In S. Kanazawa's evolutionary theory of general intelligence (g), g is presented
      as a species-typical information-processing mechanism. This conceptualization of
      g departs radically from the accepted conceptualization of g as a source of
      individual differences that is manifest in the positive manifold. Kanazawa's
      theory is thus problematic in the sense that it concerns a purely hypothetical,
      and empirically unsupported, conceptualization of g. The authors argue that an
      evolutionary account of g should address it as a source of individual differences
      -that is, in a manner that is consistent with the empirical support for g.

PMID- 16637770
TI  - The annihilated self.

PMID- 16637769
TI  - Some thoughts about schizoid dynamics.

PMID- 16637771
TI  - Metaphor and trauma: the bag lady and her bag of jewels.

PMID- 16637772
TI  - "I will not let you go unless you bless me": wrestling with the Angel of History
      in the aftermath of analytic work between a German-Jewish-descended analyst and a
      German-Nazi-descended patient.

PMID- 16637773
TI  - Some determinants of the multigenerational transmission process.

PMID- 16637774
TI  - Potential influence of racism and skin tone on early personality formation.

PMID- 16637775
TI  - "With sorrow you will have sons": the constructive consequence of maternity
      blues.

PMID- 16637782
TI  - The metabolic syndrome and cardiometabolic risk: scope of the problem and current
      standard of care.
AB  - The metabolic syndrome is a public health concern because its prevalence is
      increasing in the United States, and it is associated with cardiovascular
      morbidity and mortality. We discuss epidemiologic trends in and causes of the
      metabolic syndrome. The relationships among the cardiometabolic risk factors that
      contribute to the metabolic syndrome-obesity, insulin resistance, proinflammatory
      and prothrombotic states, atherogenic dyslipidemia, and hypertension-and between
      these risk factors and cardiovascular morbidity and mortality are explained.
      Currently available interventions to modify these risk factors and the importance
      of preventive strategies and early detection efforts are also addressed.

PMID- 16637783
TI  - New and emerging strategies for reducing cardiometabolic risk factors.
AB  - Several new drug therapies with beneficial effects on more than one of the
      cardiometabolic risk factors that contribute to the metabolic syndrome have been
      developed recently or are under investigation. Emerging risk factors for coronary
      heart disease (CHD), including low concentrations of high-density lipoprotein
      (HDL) cholesterol and apolipoprotein A-1 (apoA-1), high levels of high
      sensitivity C-reactive protein, and small dense low-density lipoprotein
      cholesterol particles, have been identified. We provide a detailed description of
      the mechanisms of action and findings from clinical trials of the new drug
      therapies and discuss established drug therapies with beneficial effects on
      emerging risk factors for CHD. The new and emerging drug therapies include an
      antiobesity agent that reduces atherogenic dyslipidemia and abnormal glucose
      metabolism; cholesteryl ester transfer protein inhibitors that increase HDL
      cholesterol and apoA-1 levels; glitazars that increase HDL cholesterol and
      decrease triglyceride concentrations, as well as improve abnormal glucose
      metabolism; and the amylin analog pramlintide and the incretin mimetic exenatide,
      both of which reduce body weight as well as improve abnormal glucose metabolism.
      The insulin-sensitizing effects of angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers (ARBs), which may help prevent new-onset
      diabetes mellitus, and the beneficial effects of the ARB telmisartan on the
      glucose and lipid profiles also are presented.

PMID- 16637784
TI  - Evaluating and treating cardiometabolic risk factors: a case discussion.
AB  - Reducing the risk for coronary heart disease (CHD) requires a comprehensive
      assessment of cardiometabolic risk factors along with the initiation of
      nonpharmacologic and pharmacologic therapies to mitigate these risk factors. A
      case study is presented to illustrate the approach to evaluating a patient and
      selecting among available and emerging therapeutic modalities to reduce CHD risk.

PMID- 16637786
TI  - Changing the structure of pharmaceutical education to require doctor of pharmacy
      and postgraduate residency education and training.

PMID- 16637787
TI  - Clinical maturity in pharmacy.

PMID- 16637788
TI  - Against the wind.

PMID- 16637789
TI  - Adverse drug reactions in United States hospitals.
AB  - Adverse drug reactions (ADRs) were examined in 8,208,960 hospitalized Medicare
      patients in 1998. A database was constructed from the 1998 MedPAR database. The
      study population was composed of 141,398 Medicare patients who experienced an ADR
      (rate of 1.73%). The most common drug classes associated with ADRs were
      cardiotonic glycosides, adrenal corticosteroids, antineoplastic agents,
      anticoagulants, and analgesics. The most common associated diagnoses were
      hypertension, congestive heart failure, atrial fibrillation, volume depletion
      disorders, and atherosclerotic heart disease. In patients who experienced an ADR,
      death rates were 19.18% higher with 1971 excess deaths (odds ratio 1.208, 95%
      confidence interval 1.184-1.234), and length of hospital stay was 8.25% higher
      with 77,769 excess patient-days (Mann-Whitney U test [U]=200078720610, p<0.0001).
      Charges for patients with an ADR were increased as follows: total Medicare 19.86%
      (339,496,598 US dollars, U=200,089,611,739, p<0.0001), drugs 9.15% (24,744,650 US
      dollars, U=208,719,928,502, p<0.0001), and laboratory charges 2.82% (6,221,512 US
      dollars, U=195,143,498,450, p<0.0001). We developed a list of high-risk diagnoses
      and drug classes to help pharmacists target patients who are more likely to
      experience ADRs. This is the first study to evaluate the ADRs in a large
      population of hospitalized Medicare patients. These findings will enable
      pharmacists to develop better management programs for ADRs.

PMID- 16637790
TI  - Cost-effectiveness analysis of antithrombotic therapy in nonurgent percutaneous
      coronary intervention.
AB  - STUDY OBJECTIVE: To perform a cost-effectiveness analysis comparing three
      treatment approaches during nonurgent percutaneous coronary intervention (PCI):
      bivalirudin with provisional glycoprotein (GP) IIb-IIIa inhibitor therapy,
      unfractionated heparin (UFH) with eptifibatide, and UFH with abciximab. DESIGN:
      Literature-based decision model from an institutional perspective. DATA SOURCE:
      Patient data from the Randomized Evaluation in PCI Linking Angiomax to Reduced
      Clinical Events (REPLACE)-2 study and three other randomized controlled trials
      that included UFH and routine GP IIb-IIIa inhibitor (eptifibatide or abciximab)
      therapy. All included studies were comparable based on patient population,
      procedural techniques, and general treatment approaches. MEASUREMENTS AND MAIN
      RESULTS: We included patient populations undergoing contemporary nonurgent PCI to
      identify probabilities of success or complications (myocardial infarction, urgent
      revascularization, thrombocytopenia, and major or minor bleeding at 30 days).
      Costs were assigned to each outcome by incorporating diagnosis-related group--
      and/or Current Procedural Terminology--associated costs, institutional drug
      acquisition costs, and unit replacement costs of platelets and red blood cells.
      In the base-case analysis, the use of bivalirudin with provisional GP IIb-IIIa
      inhibitor therapy dominated the UFH and planned GP IIb-IIIa inhibitor approach:
      UFH with eptifibatide was 74 US dollars more expensive and 1.2% less effective,
      and UFH with abciximab was 777 US dollars more expensive and 2.3% less effective.
      Sensitivity analyses indicated that the model results were robust, but also
      revealed that bivalirudin lost its cost-effectiveness, resulting in UFH with
      eptifibatide becoming more cost-effective, when two or more vials of bivalirudin
      were necessary in greater than 27% of cases or when the use of provisional GP IIb
      IIIa inhibitor therapy exceeded 20%. CONCLUSION: This analysis indicates that
      bivalirudin with provisional GP IIb-IIIa inhibitor therapy is the most cost
      effective antithrombotic treatment strategy in nonurgent PCI when its use and
      dosing are consistent with the REPLACE-2 trial.

PMID- 16637791
TI  - Randomized trial to improve laboratory safety monitoring of ongoing drug therapy
      in ambulatory patients.
AB  - STUDY OBJECTIVE: To determine whether an electronic tool effectively increases
      the percentage of patients receiving laboratory monitoring during ongoing drug
      therapy. DESIGN: Randomized trial. SETTING: Outpatient medical offices of a group
      model health maintenance organization. PATIENTS: A total of 9,139 patients
      prescribed ongoing therapy with any of 14 drugs, resulting in 4,871 patient-drug
      combinations in the intervention group and 4,780 in the usual-care (control)
      group. INTERVENTION: Physicians and pharmacists jointly developed monitoring
      guidelines based on published recommendations. Pharmacists were electronically
      alerted to missing laboratory results and then ordered tests, reminded patients
      to undergo tests, and reviewed and managed abnormal results. MEASUREMENTS AND
      MAIN RESULTS: In the intervention group, 64% of patientdrug combinations were
      monitored, whereas in the usual-care group 58% were monitored (p < 0.001).
      Differences in monitoring were observed in the intervention versus usual-care
      groups for amiodarone (71% vs 55%, p<0.01), theophylline (54% vs 28%, p<0.001),
      carbamazepine (49% vs 32%, p<0.001), lithium (42% vs 28%, p<0.01), phenytoin (44%
      vs 33%, p<0.001), and metformin (72% vs 67%, p<0.001). Of 1981 laboratory tests
      ordered, 1,472 (74%) were completed. The tests revealed 181 serum drug
      concentrations outside the therapeutic range and 126 abnormal serum creatinine,
      alanine aminotransferase, aspartate aminotransferase, and thyroid-stimulating
      hormone levels, and complete blood counts. CONCLUSION: A computerized tool plus
      collaboration of health care professionals effectively increased the number of
      patients who received laboratory safety monitoring of drug therapy.

PMID- 16637792
TI  - Lack of pharmacokinetic interaction between lamotrigine and olanzapine in healthy
      volunteers.
AB  - STUDY OBJECTIVE: To investigate the potential drug-drug interaction between
      lamotrigine, an antiepileptic agent used to treat bipolar disorders, and
      olanzapine, an atypical antipsychotic drug also used to treat bipolar disorders,
      both of which are metabolized by the uridine diphosphate glucuronosyltransferase
      system. DESIGN: Prospective cohort study. SETTING: University center for clinical
      research. SUBJECTS: Fourteen nonsmoking, healthy volunteers. INTERVENTION:
      Subjects received lamotrigine 25 mg/day for 5 days, then 50 mg/day for 10 days to
      achieve steady-state concentrations. On day 15, blood samples were obtained
      before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the dose.
      Lamotrigine 50 mg/day was then given for an additional 3 days. On the next day,
      lamotrigine 50 mg and olanzapine 5 mg were coadministered. Blood samples were
      obtained at the same times as before and at 48, 72, and 96 hours after dosing.
      MEASUREMENTS AND MAIN RESULTS: Blood samples were assayed for lamotrigine and
      olanzapine concentrations by means of high-performance liquid chromatography.
      Olanzapine did not significantly affect lamotrigine disposition, as we observed
      no differences in the area under the concentration-time curve from 0-24 hours or
      in lamotrigine plasma concentrations at baseline or at 24 hours. For lamotrigine,
      the mean time to reach maximum concentration was significantly prolonged during
      olanzapine coadministration (mean +/- SD 1.9 +/- 1.3 vs 4.0 +/- 3.0 hrs, p =
      0.025), possibly because of the anticholinergic properties associated with
      olanzapine. Mild sedation was the only adverse effect that occurred during
      lamotrigine and olanzapine coadministration. CONCLUSION: Lamotrigine and
      olanzapine can safely be combined in healthy volunteers at the low doses studied,
      without a clinically significant interaction. When prescribing high doses of
      olanzapine and lamotrigine for bipolar disorder, patients must be carefully
      monitored.

PMID- 16637793
TI  - Potential interactions between prescription drugs and complementary and
      alternative medicines among patients in the emergency department.
AB  - STUDY OBJECTIVE: To determine the nature and prevalence of potential interactions
      between prescription drugs and complementary and alternative medicines (CAMs) and
      the reasons some patients do not advise their physicians of CAM use. DESIGN:
      Cross-sectional survey. SETTING: The emergency department of the Royal Melbourne
      Hospital, a tertiary referral center. PATIENTS: Four hundred four adult patients
      (>or= 18 yrs) who visited the emergency department between February 1, 2002, and
      March 31, 2003. Intervention. A specifically designed, self-administered
      questionnaire, available in seven languages. MEASUREMENTS AND MAIN RESULTS: Main
      outcome measures were the prevalence of potential prescription drug-CAM
      interactions and the reasons some patients do not advise their physicians of CAM
      use. Mean +/- SD patient age was 50.6 +/- 20.0 years; 220 patients were men
      (54.5%, 95% confidence interval [CI] 49.5-59.4%). When asked about use during the
      previous year, 275 patients (68.1%, 95% CI 63.2-72.5%) reported having taken a
      CAM; of these, 138 were also taking a prescription drug. We identified 15
      documented potential drug-CAM interactions in nine patients (3.3% of CAM users,
      95% CI 1.6-6.3%) and 97 theoretical potential drug-CAM interactions in 51
      patients (18.6% of CAM users, 95% CI 14.2-23.8%). Aspirin and warfarin were the
      most commonly involved drugs. Of CAM users, 197 (71.6%, 95% CI 65.9-76.8%) never
      informed their physician about CAM use, most frequently because they were not
      asked. CONCLUSION: The prevalence of potential drug-CAM interactions among
      patients in the emergency department is considerable, and some of these
      interactions could be clinically significant. Practitioners should increase their
      awareness of potential drug-CAM interactions, and education initiatives aimed at
      encouraging patient-physician discussion of CAM use are recommended, such as a
      CAM history in their patient evaluation. Further research is required to better
      determine the clinical significance of drug-CAM interactions.

PMID- 16637794
TI  - Pemetrexed, a novel antifolate therapeutic alternative for cancer chemotherapy.
AB  - Pemetrexed is a newly approved antifolate agent for the treatment of malignant
      pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). We
      performed a PubMed/MEDLINE database search to identify relevant literature from
      January 1966-April 2005. Bibliographies from identified references were searched
      as well, as were abstracts from the 2004 and 2005 proceedings of the American
      Society of Clinical Oncology. We discuss the pharmacology of pemetrexed,
      describing its mechanism of action and comparing it with methotrexate. The
      pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a
      better understanding of the properties of this drug. Therapeutic uses are
      assessed, beginning with the approved indications of MPM and NSCLC. However,
      pemetrexed has been studied in numerous phase II trials for other types of solid
      malignancies, and completed trials are reviewed. Data on adverse effects and drug
      interactions are also provided. Finally, dosing and administration are reviewed,
      including appropriate premedication. Premedication, including administration of
      steroids and vitamin supplements, has been shown to decrease the frequency and
      severity of pemetrexed toxicities. Pemetrexed should be used as a standard of
      care for unresectable MPM and recurrent metastatic NSCLC.

PMID- 16637795
TI  - Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone
      metastases, and hypercalcemia of malignancy.
AB  - Ibandronate is an experimental intravenous bisphosphonate under study for the
      prevention or treatment of osteoporosis and skeletal complications of bone
      metastases, as well as hypercalcemia of malignancy. To review the data on this
      drug, PubMed/MEDLINE was searched for pertinent studies in English; data from
      January 1986-October 2005 were reviewed. In preclinical studies, ibandronate was
      an extremely potent bisphosphonate compared with its predecessors and was active
      in all animal models of human postmenopausal and corticosteroid-associated
      osteoporosis. Similar to other bisphosphonates, ibandronate exhibits antitumor
      activity and prevents or reduces bone metastases. Forty to fifty percent of the
      dose is bound to bone; renal clearance of unchanged drug accounts for 70% of
      total body clearance. Early clinical trials demonstrated efficacy and
      tolerability of intravenous ibandronate in the prevention or treatment of
      postmenopausal and corticosteroid-associated osteoporosis when administered once
      every 3 months. Intravenous ibandronate also reduces skeletal complications of
      bone metastases, including pain, although the cumulative dose used is much higher
      than that used in osteoporosis, as the drug is administered every 3-4 weeks.
      Single doses of intravenous ibandronate are probably also effective in the
      treatment of hypercalcemia of malignancy. The major tolerability issue with
      intravenous bisphosphonates is renal safety, thus the drugs generally require
      infusion (e.g., 0.25 hr for zoledronic acid, 2-24 hrs for pamidronate). However,
      intravenous ibandronate can be administered by bolus injection over a few minutes
      without an elevated risk of nephrotoxicity. The experimental intravenous dosage
      is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg
      every 3-4 weeks or in a single dose for treatment of bone metastases or
      hypercalcemia of malignancy, respectively. Ibandronate can be used in the
      presence of severe renal impairment with proper dosage adjustment. The drug will
      be an interesting addition to the available drugs for osteoporosis, bone
      metastases, and hypercalcemia of malignancy. Studies of intravenous ibandronate
      as an adjunctive treatment for cancers that tend to metastasize to bone are under
      way. Whether intravenous ibandronate will be a therapeutic advance is best
      answered by randomized, controlled trials. These are ongoing and should provide
      data with which to make better-informed choices concerning intravenous
      bisphosphonates.

PMID- 16637796
TI  - High frequency of highly active antiretroviral therapy modifications in patients
      with acute or early human immunodeficiency virus infection.
AB  - STUDY OBJECTIVES: To examine the frequency of highly active antiretroviral
      therapy (HAART) modifications, the reasons for these modifications, and
      toxicities of these drugs in patients receiving their first HAART regimen after a
      diagnosis of acute (< 2 mo from infection) or early (2-12 mo) human
      immunodeficiency virus (HIV) infection. PATIENTS: Fifty-one patients who were
      enrolled in the Acute Infection and Early Disease Research Program at a
      Baltimore, Maryland, site between January 1, 1998, and April 30, 2002, and who
      chose to start HAART. MEASUREMENTS AND MAIN RESULTS: Time from initiation of
      therapy to first modification-defined as change in any HAART drug without an
      interruption in therapy or as simultaneous discontinuation of all drugs within
      the regimen-and time from initiation of therapy to reinitiation of therapy were
      recorded, as well as reasons for modification and reinitiation. With a median
      follow-up of 1,549 days, 21 (41%) of 51 patients received HAART continuously, but
      only 10 (20%) continued to receive their original regimen without any
      modification. Among the 41 patients (80%) who received modified therapy, the main
      reasons for the first modification were toxicity (16 patients), nonadherence (8),
      and new data on treatment efficacy or safety (8). Of 30 patients who stopped
      HAART, 18 restarted HAART at a later time. CONCLUSION: The high frequency of
      treatment modification among patients treated after acute or early HIV infection
      underscores the importance of determining the usefulness of antiretroviral
      therapy early in HIV infection, and the need for more tolerable regimens if HAART
      is to be started at this stage.

PMID- 16637797
TI  - 5-year evaluation of electronic medical record flag alerts for patients
      warranting secondary prevention of coronary heart disease.
AB  - STUDY OBJECTIVES: To assess the effect of flag alerts that were placed in
      electronic medical records on patients' adherence with National Cholesterol
      Education Program (NCEP) guidelines for secondary prevention of coronary heart
      disease. A secondary objective was to identify the proportion of patients who
      were prescribed lipid-lowering agents and assess the barriers of patients who did
      not reach low-density lipoprotein cholesterol (LDL) goals 5.6 years after the
      intervention. DESIGN: Retrospective analysis of a prospective medical record
      intervention. SETTING: University-based primary care clinic. PATIENTS: Eighty
      nine adult patients with atherosclerotic vascular disease. INTERVENTION: For each
      patient identified as needing secondary prevention for coronary heart disease
      according to NCEP guidelines, flags were inserted into the patient's electronic
      medical record. MEASUREMENTS AND MAIN RESULTS: Baseline patient data were
      collected. After 5.6 years, we performed a retrospective analysis. At that time,
      72 patients were evaluated; 17 were lost to follow-up. Fifty-four percent of
      patients (39 of 72 patients) had reached their LDL goal compared with 25% (16 of
      64 patients for whom complete lipid panels had been obtained) at baseline
      (p=0.001). The proportion of patients prescribed lipid-lowering agents rose from
      16% at baseline to 75% at follow-up (p=0.0001). However, 33 patients (46%) were
      above their LDL goal levels at follow-up. Reasons for failure to reach LDL goal
      were as follows: drug dosage not titrated (10 patients [30%]), adverse drug
      reaction (four patients [12%]), planned to adjust therapy in the future (three
      patients [9%]), high drug cost (two patients [6%]), drug contraindicated (two
      patients [6%]), and non-compliance (one patient [3%]). In 11 patients (33%), the
      reason for failure was not addressed in the progress notes. Thus, inadequate drug
      dosage titration (dosage not titrated, planned to adjust therapy, and reason not
      addressed [assume no action]) occurred in more than 70% of these patients.
      CONCLUSIONS: These findings emphasize the need for regular evaluation of
      patients' lipid panels followed by appropriate therapy titration to reach LDL
      goals. Further study of factors influencing cholesterol management and methods to
      improve adherence is needed.

PMID- 16637798
TI  - American College of Clinical Pharmacy's vision of the future: postgraduate
      pharmacy residency training as a prerequisite for direct patient care practice.

PMID- 16637799
TI  - Burning mouth syndrome: clinical presentation, diagnosis and treatment.
AB  - Burning mouth syndrome is an oral dysaesthesia presenting as a burning sensation
      of the tongue and less frequently other oral and peri-oral sites. There may be
      other coincident symptoms and signs, but the defining feature is the absence of
      any obvious organic cause. Because of this the condition frequently remains
      unrecognized for extended periods with a variable progression of symptoms. The
      current paper describes the complex presentation of burning mouth syndrome with
      the major aim of increasing recognition.

PMID- 16637800
TI  - Recent developments in the treatment of adult atopic dermatitis.
AB  - Atopic dermatitis is a common inflammatory skin condition with increasing
      incidence in recent decades. The mainstay of treatment has been the combination
      of emollients and topical corticosteroids, with the addition of systemic
      therapies in severe cases. New drugs such as the topical calcineurin inhibitors
      have shown promise in treating mild-to-severe atopic dermatitis. Other novel
      therapies that have been reported in the literature include leukotriene
      antagonists, monoclonal antibodies such as infliximab, leflunomide, recombinant
      interferon gamma and intravenous immunoglobulin. This review will focus on the
      treatment of adult atopic dermatitis.

PMID- 16637801
TI  - Hypothesis that embolization is an important mechanism in the laser destruction
      of cutaneous vascular lesions.
AB  - It is hypothesized that laser-induced red blood cell aggregations form emboli
      that assist in the therapeutic effect of lasers on vascular lesions.

PMID- 16637802
TI  - Retrospective analysis of adult patients with cutaneous leukocytoclastic
      vasculitis.
AB  - A retrospective analysis was conducted on 93 adult patients with cutaneous
      leukocytoclastic vasculitis from St. Vincent's Hospital Melbourne to determine
      the classification, aetiology, severity and prognosis of this population of
      patients. We developed a new classification system for the purposes of our study
      based on modifications to the Chapel Hill Consensus Conference definitions for
      vasculitic syndromes. The results of our study indicate that an obvious cause was
      not found in 44.1% of patients. Of the patients with secondary vasculitis, the
      commonest causes were drugs and infections, accounting for a total of 40.9% of
      patients. Extracutaneous involvement was found in 39.8% of patients. Patients
      with symptoms resolving in less than 3 months accounted for 59.1% of the
      population, whereas 24.8% of patients had either symptoms lasting three or more
      months or evidence of recurrent symptomatology. There were 6 deaths (6.91%) and
      the rest were lost to follow up. The majority of patients in this retrospective
      series were classified as having hypersensitivity vasculitis, which is a
      relatively benign disorder limited mostly to skin with a low incidence of
      extracutaneous involvement (15.8%). Nevertheless, evidence of systemic
      involvement or sepsis need to be excluded as this may have important implications
      for patient treatment and outcome.

PMID- 16637803
TI  - Skin care in occupational contact dermatitis of the hands.
AB  - A survey of patients attending an occupational dermatology clinic with suspected
      occupational contact dermatitis affecting the hands was undertaken to determine
      if optimal skin care treatment had been instituted prior to referral for patch
      testing. Appropriate treatment for contact dermatitis of the hands was defined as
      concurrent use of a soap substitute, use of a lipid-rich moisturizer, and if
      appropriate, use of a topical corticosteroid in an ointment vehicle. Patients
      were asked about the use of a particular soap substitute, the name and type of
      any moisturizer used and the name and type of topical corticosteroids currently
      used. The products were examined where possible. Only one-third of all patients
      were using the complete package at the time of their clinic appointment. Nearly
      all of these patients had seen a dermatologist prior to this appointment. Of the
      group of patients with work-related diseases who reported having seen a
      dermatologist prior to the clinic appointment, only 38% were using the complete
      skin care routine.

PMID- 16637804
TI  - One-fifth of basal cell carcinomas have a morphoeic or partly morphoeic
      histology: implications for treatment.
AB  - A retrospective analysis of the histopathology reports for all first or single
      basal cell carcinomas (1567) surgically treated over a 13-year period, was
      undertaken. Basal cell carcinomas classified by standard skin pathology
      nomenclature were divided into three groups: purely morphoeic basal cell
      carcinomas, partly morphoeic basal cell carcinomas and non-morphoeic basal cell
      carcinomas. A morphoeic or partly morphoeic histology was reported in 21.8% of
      basal cell carcinomas, particularly on the head and neck and in those over the
      age of 64 years. This percentage may increase further as patients live longer,
      and has important implications for treatment selection.

PMID- 16637805
TI  - Seborrhoeic keratosis and malignancy: collision tumour or malignant
      transformation?
AB  - A retrospective study of 813 histological specimens reported as seborrhoeic
      keratoses included 43 (5.3%) associated with non-melanoma skin cancer.
      Intraepidermal carcinoma (squamous cell carcinoma in situ) was the most common of
      these (36). There were five basal cell carcinomas (one with intraepidermal
      carcinoma also) and two invasive squamous cell carcinomas. No melanomas were
      reported. Twenty-seven of the intraepidermal carcinomas appeared to arise within
      the seborrhoeic keratosis as did one of the invasive squamous cell carcinomas. Of
      these 28 lesions, the head was the most common site. Fourteen were clinically
      diagnosed as a non-melanoma skin cancer with only nine clinically felt to be a
      seborrhoeic keratosis. These lesions may represent malignant transformation
      within the seborrhoeic keratosis. Twelve specimens reported adjacent dual
      pathologies, with the trunk and limbs the most common sites. Seven were diagnosed
      clinically as a skin malignancy, whereas three were thought to be solar
      keratoses. Clinically, the remaining two were seborrhoeic keratoses. The origin
      of the malignancy in these cases is less obvious and may represent collision
      tumours. Three curette specimens could not be assessed for architecture.

PMID- 16637806
TI  - Seborrhoeic keratoses with associated lesions: a retrospective analysis of 85
      lesions.
AB  - Seborrhoeic keratoses are benign epidermal neoplasms that are rarely associated
      with other skin lesions especially malignancies. In this study, the aim was to
      assess the incidence of associated lesions occurring either adjacent to or
      contiguous with a seborrhoeic keratosis. A retrospective case series over a 12
      month period was carried out. In total, 639 consecutive histologically diagnosed
      seborrhoeic keratoses were identified, of which 85 (9%) were found to be
      associated with other lesions. Of these associated lesions, 44 (7%) were
      malignant, with four of these found to be arising within the seborrhoeic
      keratosis. These associated lesions included premalignant lesions, malignancies,
      melanocytic lesions and miscellaneous lesions. Men (59%) were affected more
      commonly than women. The average age was 74 years (range 33-98 years).
      Seborrhoeic keratoses associated with other lesions were found most commonly on
      the head and neck. The incidence of associated lesions, in particular malignancy
      arising within seborrhoeic keratoses may be higher than previously thought. This
      may be an incidental phenomenon, or seborrhoeic keratosis could represent a
      precursor lesion. Therefore, seborrhoeic keratoses that have undergone recent
      clinical change should be considered for biopsy and histological examination.

PMID- 16637807
TI  - Severe toxic epidermal necrolysis precipitated by amphetamine use.
AB  - A 48-year-old man presented with a maculopapular truncal rash 9 days following
      intravenous amphetamine use. He subsequently developed widespread bullae over his
      trunk and upper limbs. Treatment was initially commenced with intravenous
      hydrocortisone. A diagnosis of toxic epidermal necrolysis was made and the
      treatment was changed to intravenous immunoglobulin at a lower dose than
      requested. At the height of the reaction, there was 90% body surface area
      involvement with tri-mucosal involvement. His response to the intravenous
      immunoglobulin was poor and was complicated by infection with methicillin
      resistant Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa.
      Gradual re-epithelialization took place over the next 6 weeks.

PMID- 16637808
TI  - Chronic urticaria due to Blastocystis hominis.
AB  - A 24-year-old woman had a 9-week history of second to third daily urticaria that
      began after an episode of contact urticaria to topical bufexamac. She was found
      to have an underlying gastrointestinal infection with Blastocystis hominis. This
      was thought to be clinically relevant as she had a history of mild chronic
      diarrhoea. After treatment of the Blastocystis hominis, her urticaria ceased.
      This could indicate the importance of performing stool microscopy and culture on
      all patients with chronic urticaria of unknown aetiology. The relationship of
      urticaria to intestinal parasites and the possibility that non-steroidal anti
      inflammatory medications could act as cofactors that help precipitate an
      urticarial reaction is discussed.

PMID- 16637809
TI  - Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease
      in a HIV-positive individual.
AB  - A 54-year-old HIV-positive homosexual man presented with erythematous and
      pigmented plaques on background erythema in the perianal region, histologically
      consistent with Bowen's disease. Perianal Bowen's disease represents high-grade
      anal intraepithelial neoplasia, which is considered a precursor lesion of
      invasive anal squamous cell carcinoma. This patient's anal intraepithelial
      neoplasia was unresponsive to multiple treatment modalities including
      cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5
      aminolaevulinic acid photodynamic therapy. He progressed to develop a poorly
      differentiated squamous cell carcinoma of the anus three and a half years after
      the Bowen's disease was diagnosed. The squamous cell carcinoma was treated with
      combined chemoradiation. A recurrence of high-grade anal intraepithelial
      neoplasia was noted 6 months after completion of chemoradiation.

PMID- 16637810
TI  - Successful treatment of type I adult-onset pityriasis rubra pilaris with
      infliximab.
AB  - A 59-year-old woman presented with a painful, pruritic eruption that had
      commenced as an erythematous, dry patch on the upper back but progressed to
      erythroderma. Examination revealed orange-tinged erythroderma, scalp scaling,
      ectropion, palmoplantar keratoderma and nail changes. A diagnosis of type I adult
      onset pityriasis rubra pilaris was made, and a subsequent skin biopsy was
      consistent with this. She was treated with a number of topical and systemic
      agents with minimal improvement or major side-effects. The patient was then
      treated with intravenous infliximab 5 mg/kg. She improved dramatically within 2
      weeks and was no longer erythrodermic. Five further infusions resulted in
      additional improvement. Methotrexate was briefly added to the regime, but was
      ceased owing to nausea. Topical tar and keratolytics were used on the scalp. The
      patient was left with minimal disease activity and was maintained on emollients.

PMID- 16637811
TI  - Multiple periungual pyogenic granulomas following systemic 5-fluorouracil.
AB  - A 65-year-old man presented with a 7-month history of eight bleeding periungual
      lesions on both feet. The clinical diagnosis of multiple pyogenic granulomas was
      confirmed by histological examination. Historically, the pyogenic granulomas
      appeared 3 months after commencing 5-fluorouracil chemotherapy for rectal
      carcinoma, suggesting a possible causative relationship. Chemotherapy was ceased
      by the supervising oncologist. Resolution occurred after two lesions had been
      treated with curettage and diathermy, and the remaining lesions with occlusive
      dressings over Kenacomb ointment (triamcinolone acetonide 0.1%, neomycin sulphate
      0.25%, gramicidin 0.025%, nystatin 100,000 U/g) topically twice daily for a
      period of 3 months.

PMID- 16637812
TI  - Pseudoporphyria secondary to narrowband UVB phototherapy for psoriasis.
AB  - A 59-year-old woman undergoing narrowband UVB phototherapy for treatment of
      psoriasis presented suddenly with tense blisters on both hips. The blisters were
      asymptomatic and disappeared within 24 hours. Histopathology together with a
      negative porphyrin screen made the diagnosis of pseudoporphyria. Blood tests
      including a full blood count, urea and electrolytes, liver function tests and
      antinuclear autoantibodies were normal. The patient was otherwise healthy; there
      was no history of extensive sun exposure, sunbeds or medication with non
      steroidal anti-inflammatory drugs. This presentation of pseudoporphyria secondary
      to narrowband UVB radiation is unusual, as UVB radiation is not known to be
      associated with pseudoporphyria.

PMID- 16637813
TI  - Colloid milium arising on a non-sun-exposed area in an adult.
AB  - A 59-year-old woman presented with multiple translucent papules on the inner
      surface of the tragus of the right ear. Initially they were treated with
      cryotherapy, with a later biopsy revealing the diagnosis of colloid milium. The
      histology was unusual for adult colloid milium as the lesion lacked a Grenz zone
      and evidence of solar elastosis. This together with a lack of aetiological
      factors made it difficult to classify the subtype of colloid milium.

PMID- 16637814
TI  - Useful subcutaneous suture technique to optimize wound edge apposition and avoid
      'dog ears'.
AB  - The key to obtaining excellent scars is perfect wound edge apposition with little
      or no tension across the sutured wound. Unsightly 'dog ear' protrusions at the
      ends of the wound should be avoided as they can detract from the cosmetic result.
      A simple, practical and efficient surgical technique is described, which can
      provide the optimal conditions for a perfect scar.

PMID- 16637815
TI  - Occupational allergic contact dermatitis to cobalt octoate included as an
      accelerator in a polyester resin.
AB  - A 46-year-old woman, who worked as a laminator of spa baths, presented with hand
      dermatitis, which was suspected to be related to her occupation. Patch testing
      revealed strong reactions to both cobalt chloride and a polyester resin that the
      patient had been using at her workplace. She also reacted to latex and had been
      wearing cotton gloves underneath rubber gloves at work. It was later discovered
      that cobalt octoate (synonym: cobalt-2-ethylhexanoate), a compound not listed on
      the manufacturer's material safety data sheet, was included as an accelerator in
      the polyester resin. She was then tested to cobalt octoate, which was also
      strongly positive. Her successful treatment included protection of her hands at
      work with cotton lined PVC gloves. This case highlights the role of cobalt salts
      as sensitizers and their presence as accelerators used in polyester resins, and
      the importance of recognizing concomitant latex allergy that may complicate
      occupational dermatitis. It also illustrates the difficulties in relying on
      material safety data sheets to identify all possible allergens.

PMID- 16637816
TI  - Desquamating rash associated with methadone use.

PMID- 16637817
TI  - International Society for the Study of Vulvovaginal Disease abandons grading of
      vulvar intraepithelial neoplasia.

PMID- 16637821
TI  - Passive consent for clinical research in the age of HIPAA.
AB  - BACKGROUND: Federal laws and regulations, including the Health Insurance
      Portability and Accountability Act (HIPAA) of 1996, intended primarily to protect
      individuals, have been described as significant barriers to the use of clinical
      registries and other population-based tools for health care research. Although
      these regulations allow for the waiver or alteration of usual consent procedures
      when the research meets certain specific criteria, waivers and alterations are
      rarely used in health care research. METHODS: The Vermont Diabetes Information
      System is a multistate randomized trial of a quality improvement intervention
      that uses a novel alteration of informed consent to help ensure that the study
      sample is representative of the target population. Patients are notified by mail
      that they are eligible for the study and that they may opt out of the study, if
      they desire, by calling a toll-free number. RESULTS: Seven thousand five hundred
      and fifty-eight patients were invited to participate. Two hundred and ten (2.8%)
      opted out. Three patients (0.04%) filed complaints, all of which were addressed
      satisfactorily. CONCLUSIONS: Health Insurance Portability and Accountability Act
      and other federal regulations raise challenges to the use of clinical registries
      in research, but modifications to the consent process, including passive consent
      methods, are useful tools to overcome these challenges. It is possible to recruit
      a broad and representative population under current law while maintaining
      appropriate protections for research subjects.

PMID- 16637822
TI  - Quality of cardiovascular disease preventive care and physician/practice
      characteristics.
AB  - BACKGROUND: Quality of cardiovascular disease (CVD) preventive care is
      suboptimal. Recent data correlated increasing years in practice for physicians
      with lower-quality health care. OBJECTIVE: The purpose of this study was to
      assess physician awareness/adherence to national blood pressure, cholesterol, and
      CVD prevention guidelines for women according to physician/practice
      characteristics. DESIGN: Standardized online survey and experimental case studies
      were administered to 500 randomly selected U.S. physicians. Multivariable
      regression models tested physician age, gender, specialty, and practice type as
      independent predictors of guideline awareness/adherence. RESULTS: Compared with
      older physicians (50+ years), younger physicians (<50 years) reported a lower
      level of awareness of cholesterol guidelines (P=.04) and lower incorporation of
      women's guidelines (P=.02). Yet, older physicians were less likely to recommend
      weight management for high-risk cases (P=.03) and less confident in helping
      patients manage weight (P=.045) than younger physicians. Older physicians were
      also less likely to identify a low-density lipoprotein<100 mg/dL as optimal
      versus younger physicians (P=.01), as were solo versus nonsolo practitioners
      (P=.02). Solo practitioners were less aware of cholesterol guidelines (P=.04) and
      were more likely to prescribe aspirin for low-risk female patients than nonsolo
      practitioners (P<.01). Solo practitioners rated their clinical judgment as more
      effective than guidelines in improving patient health outcomes (P<.01) and more
      frequently rated the patient as the greatest barrier to CVD prevention versus
      nonsolo practitioners (P<.01). CONCLUSIONS: Though guideline awareness is high,
      efforts to promote their utilization are needed and may improve quality outcomes.
      Targeted education and support for CVD prevention may be helpful to older and
      solo physicians.

PMID- 16637823
TI  - Physician board certification and the care and outcomes of elderly patients with
      acute myocardial infarction.
AB  - BACKGROUND: Patients and purchasers prefer board-certified physicians, but
      whether these physicians provide better quality of care and outcomes for
      hospitalized patients is unclear. OBJECTIVE: We evaluated whether care by board
      certified physicians after acute myocardial infarction (AMI) was associated with
      higher use of clinical guideline recommended therapies and lower 30-day
      mortality. SUBJECTS AND METHODS: We examined 101,251 Medicare patients
      hospitalized for AMI in the United States and compared use of aspirin, beta
      blockers, and 30-day mortality according to the attending physicians' board
      certification in family practice, internal medicine, or cardiology. RESULTS:
      Board-certified family practitioners had slightly higher use of aspirin
      (admission: 51.1% vs 46.0%; discharge: 72.2% vs 63.9%) and beta-blockers
      (admission: 44.1% vs 37.1%; discharge: 46.2% vs 38.7%) than nonboard-certified
      family practitioners. There was a similar pattern in board-certified Internists
      for aspirin (admission: 53.7% vs 49.6%; discharge: 78.2% vs 68.8%) and beta
      blockers (admission: 48.9% vs 44.1%; discharge: 51.2% vs 47.1). Board-certified
      cardiologists had higher use of aspirin compared with cardiologists certified in
      internal medicine only or without any board certification (admission: 61.3% vs
      53.1% vs 52.1%; discharge: 82.2% vs 71.8% vs 71.5%) and beta-blockers (admission:
      52.9% vs 49.6% vs 41.5%; discharge: 54.7% vs 50.6% vs 42.5%). In multivariate
      regression analyses, board certification was not associated with differences in
      30-day mortality. CONCLUSIONS: Treatment by a board-certified physician was
      associated with modestly higher quality of care for AMI, but not differences in
      mortality. Regardless of board certification, all physicians had opportunities to
      improve quality of care for AMI.

PMID- 16637824
TI  - Mastery learning of advanced cardiac life support skills by internal medicine
      residents using simulation technology and deliberate practice.
AB  - BACKGROUND: Internal medicine residents must be competent in advanced cardiac
      life support (ACLS) for board certification. OBJECTIVE: To use a medical
      simulator to assess postgraduate year 2 (PGY-2) residents' baseline proficiency
      in ACLS scenarios and evaluate the impact of an educational intervention grounded
      in deliberate practice on skill development to mastery standards. DESIGN: Pretest
      posttest design without control group. After baseline evaluation, residents
      received 4, 2-hour ACLS education sessions using a medical simulator. Residents
      were then retested. Residents who did not achieve a research-derived minimum
      passing score (MPS) on each ACLS problem had more deliberate practice and were
      retested until the MPS was reached. PARTICIPANTS: Forty-one PGY-2 internal
      medicine residents in a university-affiliated program. MEASUREMENTS:
      Observational checklists based on American Heart Association (AHA) guidelines
      with interrater and internal consistency reliability estimates; deliberate
      practice time needed for residents to achieve minimum competency standards;
      demographics; United States Medical Licensing Examination Step 1 and Step 2
      scores; and resident ratings of program quality and utility. RESULTS: Performance
      improved significantly after simulator training. All residents met or exceeded
      the mastery competency standard. The amount of practice time needed to reach the
      MPS was a powerful (negative) predictor of posttest performance. The education
      program was rated highly. CONCLUSIONS: A curriculum featuring deliberate practice
      dramatically increased the skills of residents in ACLS scenarios. Residents
      needed different amounts of training time to achieve minimum competency
      standards. Residents enjoy training, evaluation, and feedback in a simulated
      clinical environment. This mastery learning program and other competency-based
      efforts illustrate outcome-based medical education that is now prominent in
      accreditation reform of residency education.

PMID- 16637825
TI  - Brief report: physicians and their personal prostate cancer-screening practices
      with prostate-specific antigen. A national survey.
AB  - BACKGROUND: There is inconclusive evidence that prostate cancer screening with
      prostate-specific antigen (PSA) reduces mortality. Although PSA testing is
      widespread, it is unknown how many physicians have taken the PSA test themselves.
      OBJECTIVE: To determine the prevalence of PSA testing among physicians. DESIGN:
      Cross-sectional survey. SUBJECTS: A nationwide stratified random sample of
      urologists (response rate 61%, n=247), Internists (response rate 51%, n=273), and
      family physicians (response rate 64%, n=249) were surveyed by mail in 2000. After
      excluding female respondents and men who either reported a positive history of
      prostate cancer or did not respond to that query, there were 146 urologists, 96
      Internists, and 118 family physicians. MEASUREMENTS: Whether physicians had
      undergone prostate cancer screening with PSA. RESULTS: Eighty-seven percent
      (155/178) of male physicians aged, 50 and older and 21% (31/150) of white male
      physicians under age 50 reported having had a PSA test. More urologists than
      nonurologists in both age groups reported having had a screening PSA test.
      CONCLUSION: Most physicians aged 50 and older report undergoing PSA testing. This
      may reflect a belief in its efficacy and contribute to its widespread use.

PMID- 16637826
TI  - Principles to consider in defining new directions in internal medicine training
      and certification.
AB  - SGIM endorses seven principles related to current thinking about internal
      medicine training: 1) internal medicine requires a full three years of residency
      training before subspecialization; 2) internal medicine residency programs must
      dramatically increase support for training in the ambulatory setting and offer
      equivalent opportunities for training in both inpatient and outpatient medicine;
      3) in settings where adequate support and time are devoted to ambulatory
      training, the third year of residency could offer an opportunity to develop
      further expertise or mastery in a specific type or setting of care; 4) further
      certification in specific specialties within internal medicine requires the
      completion of an approved fellowship program; 5) areas of mastery in internal
      medicine can be demonstrated through modified board certification and
      recertification examinations; 6) certification processes throughout internal
      medicine should focus increasingly on demonstration of clinical competence
      through adherence to validated standards of care within and across practice
      settings; and 7) regardless of the setting in which General Internists practice,
      we should unite to promote the critical role that this specialty serves in
      patient care.

PMID- 16637827
TI  - Shifting paradigms in health services research ethics. Consent, privacy, and the
      challenges for IRBs.

PMID- 16637830
TI  - Developments in molecular genetics and electrophysiology in inherited retinal
      disorders.
AB  - Retinitis pigmentosa is said to be the most frequent reason for severe visual
      handicap among young people in Scandinavia today. Developments in the fields of
      electrophysiology and molecular genetics have increased our understanding of the
      pathophysiology of these disorders and have also improved our clinical
      competence, leading to a better understanding of the patient's visual handicap
      and his or her prognosis. This represents the first step towards fulfilling our
      plan for the future, which is ultimately to cure blindness caused by the
      different forms of hereditary retinal degeneration. This review is based on 20
      years of research at the Department of Ophthalmology in Lund.

PMID- 16637831
TI  - Ophthalmological findings in a sample of Swedish children aged 4-15 years.
AB  - AIMS: To characterize ophthalmological findings in a sample of Swedish children
      aged 4-15 years. METHODS: A prospective cross-sectional comprehensive
      ophthalmological investigation was performed on a sample of 143 children (67
      girls, 76 boys) aged 4-15 years. RESULTS: Visual acuity (VA) in the better eye
      >or=1.0 (<or=0.0 logMAR) was found in 79% of subjects. None of the children had
      VA in the better eye <0.5 (>0.3 logMAR). Amblyopia was found in 0.7% of subjects.
      A total of 68% of the children had no refractive errors. Hyperopia (>or=2.0
      dioptres [D] in spherical equivalent [SE]) was found in 9% and myopia (>or=0.5 D
      SE) in 6% of children. Astigmatism (>or=0.75 D) was recorded in 22% and
      anisometropia (>or=1.0 D SE) in 3%. A total of 8% were optically corrected.
      Strabismus was recorded in 3.5%. Signs of visuoperceptual problems were reported
      in 3% of the children. CONCLUSION: This sample of Swedish children may serve as a
      comparison group regarding ophthalmological findings in children aged 4-15 years.

PMID- 16637832
TI  - Ophthalmological findings in children born after intracytoplasmic sperm
      injection.
AB  - PURPOSE: To investigate visual function and ocular morphology in children born
      after intracytoplasmic sperm injection (ICSI) and compare them with visual
      function and ocular morphology in matched children born after spontaneous
      conception. METHODS: A total of 137 children born after ICSI and 159 control
      children were examined at the age of 5 years in a blinded study. The two groups
      were matched for age, gender and maternal age. The children underwent a detailed
      ophthalmological investigation by an ophthalmologist and an orthoptist. RESULTS:
      A total of 90.4% of the ICSI children had a visual acuity (VA) in the better eye
      of >or= 0.8, compared with 93.7% of the controls (NS). No significant differences
      were found between ICSI children and controls with regard to hyperopia, myopia,
      astigmatism, heterotropia, stereoscopic vision and convergence. One child with
      Goldenhar syndrome and one with Marcus Gunn syndrome were observed in the ICSI
      group. One child in the ICSI group was treated for retinopathy of prematurity.
      CONCLUSION: In this limited study group, no significant differences in visual
      function and/or ocular morphology were found between children born after ICSI and
      matched control children at the age of 5 years.

PMID- 16637833
TI  - Ultrastructural study of extraocular muscle tendon axonal profiles in infantile
      and intermittent exotropia.
AB  - PURPOSE: To investigate the ultrastructures of tendon axonal profiles in
      infantile and intermittent exotropia. Tendon axonal profiles are composed of
      myotendinous nerve endings that are presumed to serve as sensorial receptors in
      ocular proprioception. METHODS: The study subjects included 10 patients with
      exotropia who had undergone surgery in one eye (recession and resection). They
      were divided into two equal groups. Five patients with infantile exotropia that
      had developed at under 12 months of age were allocated to group A. Another five,
      with intermittent exotropia that had developed at over 12 months of age, were
      allocated to group B. In all patients, medial recti were resected by 3-4 mm in
      order to obtain tissue samples, which were then examined under an electron
      microscope. RESULTS: In group A, we noted many axonal degenerative findings, such
      as the retraction of axons from myelin sheaths with considerable shrinkage,
      axonal disintegration, and Schwann cell proliferation. On the other hand, we
      identified three unique findings in group B: intact axons with incomplete Schwann
      cell wrapping; intact Schwann cells not associated with axons, and disorganized
      Schwann cells with shrunken axons. CONCLUSION: Different patterns of tendon
      axonal profiles were seen in association with the two types of exotropia. These
      differences may be related to the pathogenesis of these exotropia types.

PMID- 16637834
TI  - Predictive value of exfoliative cytology in pigmented conjunctival lesions.
AB  - PURPOSE: Pigmented lesions of the conjunctiva are often difficult to classify
      clinically. Exfoliative cytology may be helpful, but reliable data regarding the
      sensitivity and specificity of this test are currently lacking. We determined the
      value of exfoliative cytology with regard to pigmented conjunctival lesions.
      METHODS: A total of 294 smears from 182 patients were screened for malignancy
      within 6 months of exfoliative cytology. Smears were classified according to the
      following categories: grade 0 = insufficient material for diagnosis; grade 1 =
      normal conjunctival cells; grade 2 = melanocytes with mild atypia; grade 3 =
      melanocytes with moderate atypia, and grade 4 = melanocytes with severe atypia.
      RESULTS: The sensitivity, specificity, positive predictive value and negative
      predictive value of exfoliative cytology were 85%, 78%, 59% and 93%,
      respectively. CONCLUSION: Exfoliative cytology is a fast, easy and non-invasive
      technique that may be used in the evaluation of patients with a pigmented
      conjunctival lesion.

PMID- 16637835
TI  - Corneal penetration of simultaneously applied topical levofloxacin, norfloxacin
      and lomefloxacin in human eyes.
AB  - PURPOSE: This study was performed to assess the corneal penetration of three
      topically applied fluoroquinolones (levofloxacin, norfloxacin and lomefloxacin)
      in corneal buttons obtained from patients undergoing penetrating keratoplasty.
      METHODS: Fourteen patients received three drops each of 0.5% levofloxacin, 0.3%
      norfloxacin and 0.3% lomefloxacin (the standard clinically available
      preparations) over a 30-min interval beginning 90 mins before their scheduled
      keratoplasty. Corneal samples obtained from excised buttons at the time of
      surgery were stored at - 80 degrees until analysis. The concentration of the
      administered fluoroquinolones was measured using high-performance liquid
      chromatography. RESULTS: The mean corneal concentration of levofloxacin (4.6 +/-
      3.5 microg/g, mean +/- standard deviation) was significantly higher than that of
      lomefloxacin (2.7 +/- 1.8 microg/g, p = 0.0018) and norfloxacin (1.3 +/- 1.2
      microg/g, p = 0.00012). CONCLUSION: Levofloxacin achieves a higher mean corneal
      concentration than norfloxacin and lomefloxacin in the human cornea.

PMID- 16637836
TI  - Penetrating keratoplasty combined with posterior Artisan iris-fixated intraocular
      lens implantation.
AB  - PURPOSE: To present a new surgical technique combining penetrating keratoplasty
      and open-sky posterior iris fixation of the Artisan iris-claw intraocular lens
      (IOL) for treatment of pseudophakic bullous keratopathy in a case series of five
      patients. METHODS: A graft diameter of 8.25 mm was chosen. The formerly implanted
      angle-supported IOL was removed. The IOL was enclosed, entrapping a fraction of
      the mid-peripheral iris within the haptics whilst being held firmly with the
      implantation forceps. The corneal button was sutured to the recipient bed with 10
      0 nylon sutures. A specular microscope was used for making an endothelial cell
      count. Patients underwent an ultrasound biomicroscope (UBM) scan before and 6
      months after surgery and postoperative macular oedema was assessed by optical
      coherence tomography (OCT). The minimum follow-up was 12 months. RESULTS: Visual
      acuity (VA) improved in all five cases (mean best corrected VA was 0.4
      postoperatively versus 1.28 preoperatively). No complications were noted. The
      mean endothelial cell density obtained after 1 year was 1508 cells/mm(2). The UBM
      study showed a deep anterior chamber and an open iridocorneal angle of 360
      degrees in all cases. CONCLUSION: The implantation of the Artisan device behind
      the iris better preserves the anatomy of the anterior segment with respect to the
      iridocorneal angle.

PMID- 16637837
TI  - Improvement in colour vision parameters following successful trabeculectomy.
AB  - PURPOSE: To determine whether colour vision improves following reduction of
      intraocular pressure (IOP) in glaucoma patients. METHODS: The medical records of
      29 glaucoma patients (41 eyes) were reviewed. Inclusion criteria required
      subjects to have made more than four visits to the Glaucoma Service Laboratory
      and to undergo a thorough eye examination including a Farnsworth-Munsell 100-hue
      colour vision test and Goldmann tonometry before and after pressure lowering.
      Colour vision parameters of total error score (TES), yellow-blue score (YBS) and
      red-green score (RGS) were measured. The study group consisted of 21 eyes of
      glaucoma patients who underwent uncomplicated trabeculectomy with an IOP
      reduction of >/= 20% from baseline. The control group consisted of 21 eyes of
      glaucoma patients matched for age and colour vision, who received medication
      and/or underwent surgery with a post-intervention IOP reduction of < 20% from
      baseline. The primary outcome was a comparison of pre- and post-intervention
      colour vision parameters between the two groups. RESULTS: There was a
      statistically significant improvement in TES (43 +/- 44, p < 0.001), RGS (19 +/-
      27, p = 0.0077) and YBS (23 +/- 29, p = 0.0007) in the study group compared with
      the control group. The improvement in TES (r = 0.52, p < 0.001), RGS (r = 0.55, p
      < 0.001) and YBS (r = 0.40, p = 0.008) was correlated with the percentage of IOP
      reduction. There was no statistically significant difference between improvement
      in Y-B and R-G scores in the study group. CONCLUSION: Intraocular pressure
      reduction of >/= 20% post-trabeculectomy was associated with an improvement in
      colour vision. Colour vision tests may be useful as an adjunctive outcome measure
      for therapeutic interventions.

PMID- 16637838
TI  - Clinical evaluation of rebound tonometer.
AB  - PURPOSE: To evaluate the reliability and repeatability of intraocular pressure
      (IOP) measurements using a new rebound tonometer. METHODS: Intraocular pressure
      was measured in 42 healthy human eyes of subjects aged 18-30 years (mean +/-
      standard deviation [SD] 21.5 +/- 3.2 years) using the ICare Rebound and Goldmann
      tonometers in two separate sessions. RESULTS: Intraocular pressure measurements
      were found to read slightly, but not significantly, higher with the ICare
      tonometer compared with the Goldmann instrument in both sessions (first session:
      mean bias +/- SD + 0.50 +/- 2.33 mmHg; second session: mean bias +/- SD + 0.52 +/
      1.92 mmHg). Limits of agreement between repeated readings were +/- 5.11 mmHg for
      measurements taken with the ICare tonometer, compared with +/- 3.15 mmHg for
      measurements taken with the Goldmann method. CONCLUSION: Measurement of IOP in
      normal, healthy subjects using the ICare rebound tonometer produced a small,
      statistically insignificant, positive bias when compared with the Goldmann
      tonometer. Intersessional repeatability of IOP taken with the ICare is poorer
      than that of IOP taken with the Goldmann tonometer, but is comparable with that
      of other non-Goldman-type tonometers currently available.

PMID- 16637839
TI  - Automated flicker perimetry in glaucoma using Octopus 311: a comparative study
      with the Humphrey Matrix.
AB  - PURPOSE: We evaluated the clinical usefulness of flicker perimetry in glaucoma
      and glaucoma suspect patients using the new Octopus 311 automated perimeter.
      METHODS: A total of 52 eyes of 52 glaucoma patients, 26 eyes of 26 glaucoma
      suspect patients and 61 eyes of 61 normal subjects were examined using standard
      automated perimetry (SAP), flicker perimetry and frequency doubling technology
      (FDT) perimetry. Flicker perimetry was performed using the Octopus 311 and its
      remote software package. Suprathreshold four-zone probability strategy was used
      to classify the critical fusion frequency probability level. The classified
      levels were set at 5% and 1% of probability of normality and 5 Hz. Frequency
      doubling technology perimetry was performed using 24-2-5, 24-2-1, N-30-5, N-30-1
      screening programs using Humphrey Matrix perimetry. Standard automated perimetry
      was performed using the Humphrey field analyser program 24-2 full threshold.
      Optical coherence tomography using Stratus OCT was used for evaluating the
      retinal nerve fibre layer thickness in all glaucoma and glaucoma suspect
      patients. RESULTS: Receiver operating characteristic (ROC) curves were
      calculated. In the early stage of glaucoma, the areas under the ROC curve (AUCs)
      were 0.96 in flicker and 0.90 in Matrix perimetry. In the moderate and advanced
      stages of glaucoma, the AUCs were almost 1.0 in all tests. In glaucoma suspect
      patients, the AUC of the 5% probability level in flicker was significantly higher
      than in Matrix perimetry. CONCLUSION: The four-zone probability strategy using
      the Octopus 311 is a useful method for evaluating the flicker field in early
      glaucoma and glaucoma suspect patients.

PMID- 16637840
TI  - Corneal optics after reading, microscopy and computer work.
AB  - PURPOSE: To compare lid-induced changes in corneal optics following reading,
      microscopy and computer work. METHODS: Nine subjects with normal ocular health
      were recruited for the study. Five subjects were myopic, two were emmetropic, one
      was astigmatic and one was hyperopic. Corneal topography was measured before and
      after 60 mins of reading a novel, performing a blood cell counting task on a
      microscope and Internet searching. Corneal topography data were used to derive
      the corneal wavefront Zernike coefficients up to the fourth order. A meridian
      analysis of instantaneous corneal power along the upper 90-degree semi-meridian
      was performed to examine local changes caused by eyelid pressure. Digital
      photography was used to capture body posture and eyelid position during the
      tasks. RESULTS: Each of the three tasks showed systematically different effects
      on both the characteristics and location of corneal topography changes. Reading
      and microscopy generally exhibited larger and more centrally located changes
      compared with the computer task. Differences in wavefront aberration
      characteristics between the three tasks were apparent in both lower and higher
      order aberrations. The location of corneal distortions differed significantly
      between microscopy and computer work, with microscopy causing distortions to
      occur closer to the videokeratoscope measurement axis compared with computer work
      (p = 0.015). CONCLUSIONS: Reading, microscopy and computer work have different
      effects on corneal aberrations. The results are in agreement with the hypothesis
      that lid-induced corneal aberrations may play a role in myopia development.

PMID- 16637841
TI  - Optical coherence tomography in the detection of retinal break and management of
      retinal detachment in morning glory syndrome.
AB  - PURPOSE: To determine the efficacy of optical coherence tomography (OCT) in the
      management of retinal detachment in morning glory syndrome (MGS). DESIGN:
      Prospective, interventional case series. METHODS: Five eyes of five consecutive
      MGS patients who developed retinal detachment between August 2000 and June 2004
      were enrolled and examined by OCT at presentation of retinal detachment. Four
      eyes were found to have a slit-like break at the margin of the excavation by
      careful OCT scanning 360 degrees around the excavation. All four eyes underwent
      pars plana vitrectomy, gas injection and postoperative laser photocoagulation.
      Postoperative OCT was performed to confirm the closure of the retinal break and
      reattachment of the retina. RESULTS: Optical coherence tomography detected a slit
      like break at the margin of excavation in four of five patients. The retina
      reattached in all five eyes over the subsequent 3-50-months (average 28 months)
      follow-up period. Postoperative OCT showed retinal break closure at the margin of
      the excavation. In the one eye in which no retinal break could be detected by
      OCT, the retina was reattached after pars plana vitrectomy and removal of gel
      like tissue. CONCLUSIONS: Optical coherence tomography is beneficial in the
      detection of subtle slit-like breaks at the margin of excavation in retinal
      detachment in MGS. It provides good guidance in subsequent surgery and is very
      helpful in confirming the closure of the retinal break.

PMID- 16637842
TI  - Effect of cyclic guanosine-monophosphate on porcine retinal vasomotion.
AB  - PURPOSE: Vasomotion refers to periodic oscillations in vascular tone that ensure
      the intermittent supply of blood to adjacent microvascular units. Previous
      evidence from vessels outside the eye suggests that cyclic guanosine
      monophosphate (cGMP) is involved in the regulation of vasomotion, but it is
      unknown whether this compound has an effect on vasomotion in retinal vessels.
      METHODS: Retinal arterioles from porcine eyes were studied in a wire myograph.
      After initiation of vasomotion, the vessels were stimulated with increasing
      concentrations of the cGMP agonist 8-Br-cGMP (n = 6), the phosphodiesterase
      inhibitor zaprinast (n = 6) and the cGMP synthesis inhibitor L-NAME (n = 6). High
      concentrations of L-NAME blocked vasomotion, and control experiments (n = 20)
      using 8-Br-cGMP, S-nitroso-N-acetylpenicillamine (SNAP), adenosine and pinacidil
      were carried out to elucidate whether this effect was related to changes in the
      general tone of the vessel. Additionally, the relationship between oscillations
      in vascular tone and intracellular calcium concentration was studied. RESULTS:
      Induction of cGMP agonistic activity with either 8-Br-cGMP or zaprinast lowered
      the vasomotion frequency significantly, whereas L-NAME-induced inhibition of cGMP
      increased this frequency. Neither of the agents affected the amplitude of the
      oscillations. The control experiments indicated that the effect of cGMP on
      vasomotion frequency was independent of the accompanying increase in tone. The
      oscillations in tone during vasomotion were accompanied by similar oscillations
      in intracellular calcium concentration. CONCLUSION: Cyclic GMP lowers the
      frequency without affecting the amplitude of vasomotion in isolated porcine
      retinal arterioles.

PMID- 16637843
TI  - Risk factors for conjunctival and retinal vessel alterations in sickle cell
      disease.
AB  - PURPOSE: The aim of this study was to clarify whether the clinical, laboratory
      and genetic aspects of sickle cell disease (SCD) influence the occurrence of
      vessel alterations in the conjunctiva and retina. METHODS: A total of 102 SCD
      patients underwent biomicroscopical and retinal examination, in addition to
      evaluations of haemoglobin (Hb) and haematocrit (Ht) levels, fetal haemoglobin
      (HbF) estimations, serum creatinine and albuminuria levels, glomerular filtration
      rate (GFR) values, phenotypes, beta-globin gene haplotypes and alpha
      thalassaemia. The relationship between ocular vessel alterations and clinical,
      laboratory and genetic features were evaluated using chi-squared or Fisher tests
      and logistic regression analysis. In 13 patients on enalapril treatment, a second
      ophthalmological evaluation was performed after a 12-month period to evaluate the
      longitudinal effect of the drug on ocular vessels. RESULTS: Conjunctival vessel
      alteration (CVA) was not influenced by age, gender, HbF estimation, serum
      creatinine and albuminuria levels, GFR values, beta-globin gene haplotypes or
      alpha-thalassaemia. However, increased frequencies of CVA were found in patients
      with Hb </= 9.0 g/dl, Ht </= 26.7% and sickle cell anaemia (SS) phenotype.
      Retinal vessel alteration (RVA) was identified only in patients aged 17 years or
      older. Enalapril did not demonstrate ocular vessel amelioration after 12-months
      of daily use. CONCLUSION: The results indicate that lower Hb and Ht levels and SS
      phenotype are risk factors for CVA, and age over 17 years may be risk factors for
      RVA in SCD patients.

PMID- 16637844
TI  - Colour Doppler examination of early and late orbital haemodynamic changes in eyes
      with eyelid oedema due to blunt trauma.
AB  - PURPOSE: To evaluate the early and late alterations in orbital blood flow
      parameters in eyes with severe eyelid swelling due to blunt trauma by using
      colour Doppler ultrasonography (CDU). METHODS: Blood flow parameters in the
      ophthalmic artery (OA), central retinal artery (CRA), short posterior ciliary
      arteries (SPCAs) and central retinal vein (CRV) were examined by CDU in 62 eyes
      of 31 patients with unilateral blunt trauma and in 32 eyes of 32 normal subjects.
      Patients were examined within the first 5 days and at least 1 month after trauma.
      The traumatized eyes of patients were designated 'trauma eyes', non-traumatized
      fellow eyes were designated 'fellow eyes', and randomly chosen eyes of control
      subjects 'control eyes'. RESULTS: In the early phase, peak systolic velocity
      (PSV) and end diastolic velocity (EDV) in the OA in trauma eyes were
      statistically significantly higher than in both fellow eyes and control eyes: the
      p-values for the differences in PSV and EDV between trauma eyes and fellow eyes
      were p < 0.001 and p = 0.001, respectively, while the p-values for the
      differences in PSV and EDV between trauma eyes and control eyes were p = 0.002
      and p = 0.019, respectively). No other blood flow parameters obtained at the
      first examination in all groups were statistically different. In the late phase,
      PSV in the OA in trauma eyes was found to be higher than that in both fellow eyes
      and control eyes, but the difference was significant only between trauma eyes and
      fellow eyes (p = 0.028). End diastolic velocity in the CRA was statistically
      significantly lower in fellow eyes than in control eyes (p = 0.046). No other
      blood flow parameters in any vessels examined in fellow eyes and control eyes
      were statistically significantly different during the study period. CONCLUSION:
      Blood flow velocities detected by CDU are increased in the OA in eyes with eyelid
      oedema due to blunt trauma and some of these changes may persist for up to 1
      month. This effect seems to be a consequence of trauma-induced hyperaemia in the
      orbital soft tissues rather than an expression of traumatic choroidal
      vasculopathy.

PMID- 16637845
TI  - Correction of involutional lower eyelid medial ectropion with transconjunctival
      approach retractor plication and lateral tarsal strip.
AB  - AIM: We describe the technique and our results in managing lower eyelid
      involutional medial ectropion using a combination of lateral tarsal strip to
      address horizontal eyelid laxity, and transconjunctival inferior retractor
      plication to address inferior retractor dehiscence. METHODS: Patients with
      symptoms of epiphora or signs of medial ectropion were offered this procedure.
      All had the following characteristics: medial lower eyelid eversion, punctal
      eversion >3 mm, medial canthal tendon laxity <4 mm, significant horizontal eyelid
      laxity and lacrimal systems that were patent to syringing. RESULTS: A total of 24
      eyelids of 17 patients underwent this procedure over a 12-month period. The mean
      age of the patients was 79.7 years; 11 were male and six were female. The mean
      follow-up time was 18 months. Two eyes had undergone previous surgery. All
      patients had restoration of the eyelid margin to the globe and relief of
      symptoms. No complications were noted. DISCUSSION: These results suggest that
      excision of posterior lamellar tissue is not necessary for correction of
      involutional medial ectropion. Transconjunctival plication or reattachment of
      retractors is easy to perform and allows for the repair of more than the medial
      portion of the retractors if required.

PMID- 16637846
TI  - Polytetrafluoroethylene (Goretex) for muscle elongation in the surgical treatment
      of strabismus with restricted motility.
AB  - PURPOSE: Repeated strabismus surgery as well as eye muscle fibrosis in various
      forms of strabismus, can be followed by restriction of the motility of the eye.
      Tendon elongation may be necessary if further improvement of the deviation and
      duction of the eye muscle is to be achieved. We used polytetrafluoroethylene
      (Goretex) and looked at its user comfort, compatibility and dose-rate
      relationship. METHOD: Three patients with consecutive exotropia after repeated
      operations for congenital esotropia, two patients with VI nerve palsy and
      residual head turn after combined convergence operation and one child with
      congenital fibrosis syndrome underwent muscle tendon elongation with Goretex (7
      15 mm) of either the medial or the lateral rectus muscle, which had already been
      resected and/or recessed in former surgeries. Forced duction under general
      anaesthesia was restricted in all patients. RESULTS: The correction of the
      deviation in primary position (deviation at distance + 3 degrees to - 4 degrees
      and at near - 1 degrees to - 8 degrees ) and in side gaze was satisfactory and
      motility was clearly improved. There were no postoperative complications
      (infection, shrinkage, scarring) and the postoperative results in terms of the
      angle of deviation and the improvement in motility remained stable for 1-6 years.
      CONCLUSION: Polytetrafluoroethylene (Goretex) is a good material with which to
      resolve complicated cases of strabismus in which muscle tendon elongation for
      bulbus restriction is necessary.

PMID- 16637847
TI  - Compound heterozygous RDH5 mutations in familial fleck retina with night
      blindness.
AB  - PURPOSE: To describe the clinical features and genetic analysis of a 3-year-old
      boy diagnosed with familial fleck retina with night blindness. METHODS: The
      proband and his parents and grandparents were included. History, visual acuity
      and fundus examinations were evaluated. Bright-flash (rod-plus-cone)
      electroretinograms (ERGs) were recorded after 30 mins and 180 mins of dark
      adaptation. Mutation screening of the RDH5 gene encoding 11-cis retinol
      dehydrogenase was performed. RESULTS: The parents noticed the proband's night
      blindness when he was 2 years old. Best corrected visual acuity was 1.0 in both
      eyes. Fundus examinations revealed numerous yellow-white flecks of varying size
      and shape throughout the midperipheral to far peripheral retina in both eyes. The
      distribution, size and shape of the flecks were comparable to those seen in
      familial fleck retina with night blindness, rather than fundus albipunctatus. The
      ERGs showed extremely diminished responses after 30 mins of dark adaptation, but
      there were substantial increases in the amplitudes of both a- and b-waves when
      recorded after 180 mins of dark adaptation. Although a total of 19 RDH5 mutations
      have been found only in patients with fundus albipunctatus, compound heterozygous
      mutations, p.V177G and p.L310delinsEV, whose combination has not been previously
      reported, were found in the proband. The asymptomatic parents and one of the
      grandparents each carried one of the mutations, consistent with autosomal
      recessive transmission. CONCLUSION: Our study indicates that different mutations
      in the RDH5 gene can cause phenotypic variations of either fundus albipunctatus
      or familial fleck retina with night blindness.

PMID- 16637848
TI  - Intraocular malignant teratoid medulloepithelioma in an adult:
      clinicopathological case report and review of the literature.
AB  - PURPOSE: To report a case of intraocular medulloepithelioma, an embryonal tumour
      with extremely rare presentation in adults. METHOD: The case of a 44-year-old man
      with intraocular malignant teratoid medulloepithelioma, primarily diagnosed as
      intraocular teratoma, is described and the literature on this subject is
      reviewed. RESULTS: The patient presented with progressive proptosis caused by a
      tumour in the left eyeball. He had a 28-year history of loss of vision in the
      left eye. Histopathological examination of the enucleated eye demonstrated an
      intraocular teratoma. No adjuvant treatment was given. Six months later the
      patient presented with massive progression in the left orbit and intracranial
      invasion. Cisplatin-based chemotherapy was administered, but discontinued after
      two cycles due to poor tolerance and lack of response. At subsequent pathology
      review, a final diagnosis of malignant teratoid medulloepithelioma was made.
      Salvage radiotherapy (60 Gy in 30 fractions) resulted in partial response of the
      intracranial lesion. However, the patient died 6 months later due to intracranial
      tumour progression. CONCLUSION: Medulloepithelioma should be considered in the
      differential diagnosis of intraocular tumours in adults, especially in the case
      of coexisting, long-standing ocular symptoms. In some cases this disease is very
      aggressive.

PMID- 16637849
TI  - Diffuse granulomatous necrotizing scleritis.
AB  - CASE REPORT: A 34-year-old man presented with anterior scleral thinning in the
      right eye (RE) and a painful nodular scleritis in the left eye (LE). Fundus
      examination showed a healed vasculitis and an inferior epiretinal neovascular
      membrane in the LE. Topical and systemic oral steroids and antiviral medication
      were prescribed. One year later, optic disc hyperaemia and swelling and macular
      oedema became apparent in the LE. Pulsed intravenous steroids were administered
      for 1 year, when a nasal septum perforation and vitreous haemorrhage in the LE
      were diagnosed. The eye was enucleated 3.5 years after the initial complaint.
      Necrotizing granulomatous tissue replacing the sclera and subconjunctival
      granulomatous tissue were observed. Six months later, oedema and
      neovascularization of the right optic disc were observed and cyclophosphamide was
      started, with regression of the clinical signs. No systemic abnormalities have so
      far become apparent. DISCUSSION: Posterior scleritis is most often observed in
      patients with no signs of associated systemic autoimmune disease. The diagnosis
      in this case is most probably one of Wegener's granulomatosis (WG). In WG, the
      diagnosis is based on necrotizing granulomas of the respiratory tract,
      generalized focal necrotizing vasculitis and focal necrotizing
      glomerulonephritis. Eye involvement with WG has been reported in up to 58% of
      cases. Evaluation of the scleritis patient should include a detailed medical
      history, chest X-rays, blood tests, autoantibody serology and analysis of urinary
      sediment. Cyclophosphamide is the treatment of choice for patients with ocular
      manifestations of WG, polyarteritis nodosa or rheumatoid arthritis, either alone
      or in combination with systemic steroids. Visual loss is expected in 85% of
      individuals with severe necrotizing posterior scleritis.

PMID- 16637850
TI  - Penetrating ocular injuries in children: visual outcome and prognostic factors.

PMID- 16637851
TI  - Functional magnetic resonance imaging corresponds to Humphrey perimetry in a
      patient with pituitary adenoma.

PMID- 16637852
TI  - Intraocular pressure change following application of 1% tropicamide for
      diagnostic mydriasis.

PMID- 16637853
TI  - StratusOCT of filtering bleb after trabeculectomy.

PMID- 16637854
TI  - Pregnancy associated, optic disc drusen related visual loss.

PMID- 16637855
TI  - Photodynamic therapy in symptomatic parafoveal telangiectasia secondary to Osler
      Rendu-Weber disease.

PMID- 16637856
TI  - Bilateral anterior uveitis associated with travoprost.

PMID- 16637857
TI  - Mild hepatitis C: treat or monitor.

PMID- 16637858
TI  - Hepatitis C virus carriers with persistently normal ALT levels: biological
      peculiarities and update of the natural history of liver disease at 10 years.
AB  - Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine
      aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly
      milder disease. In order to understand the differences between CHC patients with
      elevated ALT levels compared with those with PNAL better, we compared
      epidemiological, immunological and histological findings, in particular, the
      value of proliferating hepatocyte activity (PCNA) between the two groups of
      patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased
      ALT who underwent liver biopsy for histological diagnosis and determination of
      clinical prognosis, and 24 PNAL patients under follow-up for 10 years.
      Immunological response to different HCV genomic epitopes was tested in both the
      control group and in PNAL subjects. PCNA values from liver specimens of all
      patients as well as liver biopsies of PNAL patients at time points 0 and 5 years
      were calculated according to Hall et al.Age, sex and body mass index (BMI) were
      not significantly different between the two groups. The median liver histology
      stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2
      6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not
      statistically different at the three time points considered. Interferon (IFN)
      gamma production was comparable in the two groups. PCNA was significantly higher
      in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5%
      range = 3-8%; P < 0.05) and no statistically significant differences were found
      in PNAL patients at time points 0, 5 and 10 years. This study confirms that
      progression to cirrhosis is slow or absent in PNAL patients after 10 years of
      follow-up. Accordingly, the hepatic proliferative activity index is low and seems
      to be stable over time.

PMID- 16637859
TI  - Fibrosis progression in initially mild chronic hepatitis C.
AB  - The natural history of chronic hepatitis C presenting with no/minimal liver
      fibrosis is uncertain with controversies on risk of progression and need for
      antiviral treatment. We studied rates and determinants of fibrosis progression in
      initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65
      +/- 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis
      in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively
      while untreated with repeated biopsy after 5 or more years (mean interval 7.8 +/-
      1.51 years). Patients showing fibrosis progression were compared with
      nonprogressors for baseline and follow-up parameters. Sixty-four patients (60.4%)
      showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%)
      with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1
      initially. Fibrosis progression (DeltaF/year) was associated with age (P <
      0.0001), baseline and follow-up alanine aminotransferase (ALT) (P = 0.005),
      histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy
      and use of alcohol (P = 0.008). Thus liver fibrosis progression occurs in two
      thirds of patients with initially mild chronic hepatitis C within 5-10 years and
      advanced fibrosis/cirrhosis develops in one-third of those with F1 initially.
      Fibrosis is facilitated by older age and alcohol and associated with inflammatory
      activity and ALT levels. Antiviral therapy should be considered in mild chronic
      hepatitis C.

PMID- 16637860
TI  - Diabetes mellitus in chronic hepatitis B and C: prevalence and potential
      association with the extent of liver fibrosis.
AB  - Diabetes mellitus has been reported to have an increased prevalence and to be
      associated with more severe fibrosis in patients with chronic hepatitis C. We
      evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis
      B or C as well as the possible association between presence of diabetes and
      extent of liver fibrosis. In total, 434 consecutive patients with histologically
      documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174)
      or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and
      epidemiological, somatomorphic, laboratory and histological patient
      characteristics were evaluated. Liver histological lesions were blindly evaluated
      according to the Ishak's classification. Diabetes was present in 58 (13%)
      patients, without any difference between those with chronic hepatitis B (14%) or
      C (13%). Diabetes was observed significantly less frequently in patients with
      fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The
      presence of diabetes was independently associated with higher gamma-glutamyl
      transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P
      < 0.001) as well as with presence of hepatic steatosis and increased serum
      triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was
      significantly associated with older age and higher GGT levels, but not with the
      extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10%
      of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis
      C. The presence of diabetes is strongly associated with more severe liver
      fibrosis, but such an association may be related to the high prevalence of
      diabetes in patients with cirrhosis.

PMID- 16637861
TI  - Sustained virological response rates and durability of the response to interferon
      based therapies in hepatitis C patients treated in the clinical setting.
AB  - International controlled trials have demonstrated increasing sustained
      virological response (SVR) rates to interferon-based therapies in hepatitis-C
      treated patients. Response rates of 6-20% in the era of interferon monotherapy
      are compared with 42-82% with pegylated interferon plus ribavirin. The
      virological durability of the SVR is unknown and the optimal follow-up for these
      patients is unclear. The aim of our study was to determine SVR rates and the
      durability of the response to interferon-based therapies in the clinical setting.
      From our database of 1540 hepatitis C patients, 344 treatment courses of at least
      12 weeks duration were identified, including interferon monotherapy (175
      patients), interferon plus ribavirin (96 patients) and peginterferon plus
      ribavirin (73 patients). Interferon monotherapy was associated with an SVR rate
      of 5% in 103 genotype 1 patients and 25% in 72 genotype 2/3 patients. Response
      rates were higher (P < 0.001) with interferon plus ribavirin-41% in 34 genotype 1
      patients and 73% in 62 genotype 2/3 patients-and with peginterferon plus
      ribavirin-47% in 47 genotype 1 patients and 79% in 26 genotype 2/3 patients. Of
      147 patients with an SVR, 146 (>99%) remained hepatitis C virus PCR negative
      during a mean 2.3 years (range 0.3-10.3) of follow-up. In conclusion, with
      advances in therapies, we are achieving higher response rates in hepatitis C
      patients treated in the clinical setting. We can now expect an SVR in over half
      of the treated patients. Importantly, the response is durable and medium and long
      term follow-up of these patients are of low yield and largely unnecessary.

PMID- 16637862
TI  - Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis
      patients.
AB  - Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in
      combination with ribavirin. There is limited experience with either drug in
      dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with
      HCV genotype 1, one with genotype 4 and one genotype 2 were treated with
      pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for
      24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively.
      All patients were given reduced ribavirin doses, initially 200-400 mg/day.
      Ribavirin trough plasma concentrations were measured with a HPLC method
      previously developed for earlier treatment studies, aiming at a target
      concentration of 10-15 micromol/L. Interferon related side-effects were common,
      in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with
      improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin
      induced anaemia was treated with high doses of erythropoietin and low doses of
      iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR
      negative during treatment which was completed or nearly completed in four
      patients. One patient terminated therapy prematurely due to pronounced interferon
      related side-effects and another died of myocardial infarction probably not
      related to therapy. Three patients have remained HCV-RNA negative with extended
      follow-up, two of whom have had a successful kidney transplant. Pegylated
      interferons are likely to become a valuable addition for HCV therapy in ESRD and
      are possible to combine with ribavirin. However the pharmacokinetics and
      tolerability of both peg-alfa-2a and 2b need to be studied more closely in
      prospective studies before definite dosing recommendations can be made.

PMID- 16637863
TI  - Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C
      infection.
AB  - Given that the complications of hepatitis C are due to fibrosis, we hypothesized
      that the antifibrotic effects of interferon gamma on stellate cells would lead to
      beneficial effects in patients with hepatitis C. Thus, we evaluated the safety
      and efficacy of interferon gamma-1b in patients with hepatitis C. A cohort of 20
      patients with chronic hepatitis C who failed or were intolerant to previous
      interferon-alpha-based regimens received 200 mug of interferon gamma-1b
      subcutaneously three times weekly for 24 weeks. Liver biopsy was performed prior
      to and at the end of treatment. Biopsies were evaluated by a single blinded
      pathologist using the Knodell system modified by Ishak, and fibrosis was also
      quantitated by morphometric analysis. The study population was 75% male and 70%
      Caucasian. Mean age was 47.9 +/- 7.5 years. Eighteen of 20 patients completed
      therapy. One patient discontinued therapy because of constitutional symptoms. One
      patient discontinued therapy because of elevated aminotransferases greater than
      twice baseline. No serious adverse events occurred. Morphometric analysis
      revealed that six patients (30%) had >1% absolute reduction in fibrosis score.
      Four of 20 (20%) patients had improvement in Ishak fibrosis scores after
      treatment. In conclusion, interferon gamma therapy is safe and well tolerated in
      patients with chronic hepatitis C. Although we did not detect an overall
      reduction in fibrosis, interferon gamma-1b treatment led to a reduction in
      fibrosis in selected patients. These data provide a basis for further study of
      interferon gamma-1b in patients with chronic fibrosing liver disease.

PMID- 16637864
TI  - Multicentre study of hepatitis B virus genotypes in France: correlation with
      liver fibrosis and hepatitis B e antigen status.
AB  - The clinical significance of hepatitis B virus (HBV) genotypes is still under
      debate. The aims of this study were to assess the distribution of HBV genotypes
      in France and to identify the associations between HBV genotypes and patient
      demographics, severity of liver disease and HBeAg status in patients referred to
      tertiary care centres. This was a French, multicentre, retrospective study on 262
      patients with chronic HBV infection. HBV genotypes were determined using INNO
      LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy
      samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or
      African (18%) ethnicity and 36% were HBeAg positive. All A-G genotypes were
      found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%)
      and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases.
      Genotype A was associated with sexual contact (P < 0.001) and genotype D with
      transfusion (P < 0.001) and HBe antibody positivity (P = 0.03).The distribution
      of HBV genotypes differed with regard to the ethnicity, and may reflect migration
      patterns. Genotypes A and D were the most frequent in France. Genotype A was
      associated with HBeAg positivity and genotype D with HBe antibody positivity. In
      our European patients, we find no clear association between a given HBV genotype
      and liver disease severity.

PMID- 16637865
TI  - Association of core promoter/precore mutations and viral load in e antigen
      negative chronic hepatitis B patients.
AB  - Apart from core promoter A1762T/G1764A and precore G1896A mutations, other
      hepatitis B virus (HBV) mutants are detected in hepatitis B e antigen (HBeAg)
      negative chronic hepatitis B (CHB). The aim of this study was to determine the
      effects of those mutants on clinical manifestation and viral loads of genotypes B
      and C HBV. Seventy-nine HBeAg-negative CHB patients with hepatitis flare were
      enrolled in this study and their HBV precore/core region were sequenced. Serial
      biochemical profiles and viral loads were assessed and compared. Fifty-three
      patients (67%) were infected by genotype B HBV and 26 (33%) were infected by
      genotype C HBV. The clinical manifestation and HBV viral loads were comparable
      between the two groups. However, genotype B was significantly associated with
      precore G1896A mutation (92.5%), and more mutations within nucleotide 1809-1817
      were detected in patients infected by genotype B as compared with those infected
      by genotype C (18.9%vs 3.8%). Most of the cases had mutations at the -2, -3 or -5
      position from the precore AUG initiation codon. Triple core promoter mutations
      T1753C/A1762T/G1764A [corrected] appeared to be linked to genotype C rather than
      genotype B HBV (19.2%vs 1.9%; P = 0.013). In multivariate analysis, the presence
      of either triple core promoter 1753/1762/1764 mutation or nucleotide 1809-1817
      mutation was the only factor associated with lower HBV viral load (<70 Meq/mL)
      (odds ratio = 9.01; 95% CI 1.11-71.43; P = 0.04). In conclusion, minor HBV
      variants with mutations in the core promoter and precore region were detectable
      in genotypes B and C. Such HBV variants are genotype specific and related to
      viraemia levels.

PMID- 16637866
TI  - Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients
      with acute and chronic HBV infection.
AB  - This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes
      (A-F) and their association with the G1896A precore mutation in 486 patients
      positive for HBV surface antigen. Genotypes were determined by RFLP and precore
      mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most
      common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4
      in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive
      carriers. Distribution of these genotypes was different between HBeAg+ CHB and
      HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P =
      0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine
      aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT
      (60.7%). There was a difference in genotype prevalence between chronic and acute
      infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA
      in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish
      patients as would be expected in a Mediterranean area. The unequal prevalence of
      genotypes between acute and chronic infection suggests that genotype A is
      associated with a higher tendency to cause chronic infection.

PMID- 16637867
TI  - Characteristics of HCV positive subjects referring to hospitals in Italy: a
      multicentre prevalence study on 6,999 cases.
AB  - In 2001, 6,999 anti-HCV positive subjects referred to 79 Italian hospital in a 6
      months enrollment period were evaluated. Of them, 5,632 (80.5%) tested anti-HCV
      positive alone, 1,163 (16.6%) reported also an excessive alcohol intake, and 204
      (2.9%) were also HBsAg positive. Normal biochemistry was observed in 7.8% of
      cases, chronic hepatitis in 67.9% of cases, liver cirrhosis in 18.9% of cases,
      and hepatocellular carcinoma in 3.6% cases. HCV positive subjects with excessive
      alcohol intake were statistically significantly younger, of male sex, and having
      more severe liver disease than those without excessive alcohol intake. Adjusting
      for the confounding effect of age and sex by multiple logistic regression
      analysis, HCV positive chronic hepatitis cases drinking more than four alcoholic
      drinks daily were 2.2-fold (CI 95% = 1.3-4.0) more likely to progress to liver
      cirrhosis than teetotallers. These findings indicate that nearly a quarter of HCV
      positive subjects referred to hospitals in Italy have a severe liver disease
      causing a remarkable impact on the national health system. Excessive alcohol
      intake in HCV chronic hepatitis cases increases the risk of progression to liver
      cirrhosis.

PMID- 16637868
TI  - Early effects of embryonic movement: 'a shot out of the dark'.
AB  - It has long been appreciated that studying the embryonic chick in ovo provides a
      variety of advantages, including the potential to control the embryo's
      environment and its movement independently of maternal influences. This allowed
      early workers to identify movement as a pivotal factor in the development of the
      locomotor apparatus. With an increasing focus on the earliest detectable
      movements, we have exploited this system by developing novel models and schemes
      to examine the influence of defined periods of movement during musculoskeletal
      development. Utilizing drugs with known neuromuscular actions to provoke
      hyperactivity (4-aminopyridine, AP) and either rigid (decamethonium bromide, DMB)
      or flaccid (pancuronium bromide, PB) paralysis, we have examined the role of
      movement in joint, osteochondral and muscle development. Our initial studies
      focusing on the joint showed that AP-induced hyperactivity had little, if any,
      effect on the timing or scope of joint cavity elaboration, suggesting that
      endogenous activity levels provide sufficient stimulus, and additional
      mobilization is without effect. By contrast, imposition of either rigid or
      flaccid paralysis prior to cavity formation completely blocked this process and,
      with time, produced fusion of cartilaginous elements and formation of continuous
      single cartilaginous rods across locations where joints would ordinarily form.
      The effect of these distinct forms of paralysis differed, however, when treatment
      was initiated after formation of an overt cavity; rigid, but not flaccid,
      paralysis partly conserved precavitated joints. This observation suggests that
      'static' loading derived from 'spastic' rigidity can act to preserve joint
      cavities. Another facet of these studies was the observation that DMB-induced
      rigid paralysis produces a uniform and specific pattern of limb deformity whereas
      PB generated a diverse range of fixed positional deformities. Both also reduced
      limb growth, with different developmental periods preferentially modifying
      specific osteochondral components. Changes in cartilage and bone growth induced
      by 3-day periods of flaccid immobilization, imposed at distinct developmental
      phases, provides support for a diminution in cartilage elaboration at an early
      phase and for a relatively delayed influence of movement on osteogenesis,
      invoking critical periods during which the developing skeleton becomes receptive
      to the impact of movement. Immobilization also exerts differential impact along
      the proximo-distal axis of the limb. Finally, our preliminary results support the
      possibility that embryonic hyperactivity influences the potential for postnatal
      muscle growth.

PMID- 16637869
TI  - Adaptability of elderly human muscles and tendons to increased loading.
AB  - Senile sarcopenia, the loss of muscle mass associated with aging, is one of the
      main causes of muscle weakness and reduced locomotor ability in old age. Although
      this condition is mainly driven by neuropathic processes, nutritional, hormonal
      and immunological factors, as well as a reduction in physical activity,
      contribute to this phenomenon. Sarcopenia alone, however, does not fully account
      for the observed muscle weakness, as the loss of force is greater than that
      accounted for by the decrease in muscle size. As a consequence, a reduction in
      the force per unit area, both at single fibre and at whole muscle level, is
      observed. We recently suggested that at whole muscle level, this reduction in
      intrinsic force is the result of the combined effect of changes in (1) muscle
      architecture, (2) tendon mechanical properties, (3) neural drive (reduced agonist
      and increased antagonist muscle activity) and (4) single fibre-specific tension.
      Whereas several studies support the role of the last two factors in the loss of
      intrinsic muscle force with aging, alterations in muscle architecture and in
      tendon mechanical properties have also been shown to contribute to the above
      phenomenon. Indeed, sarcopenia of the human plantarflexors, represented by a 25%
      reduction in muscle volume, was found to be associated with a 10% reduction in
      fibre fascicle length and 13% reduction in pennation angle. These architectural
      alterations were accompanied by a 10% decrease in tendon stiffness, attributable
      to alterations in tendon material properties, as suggested by a 14% decrease in
      Young's modulus. Most of these changes may be reversed by 14 weeks of resistive
      training; both fibre fascicle length and tendon stiffness were found to be
      increased by 10 and 64%, respectively. Surprisingly, however, training had no
      effect on the estimated relative length-tension properties of the muscle,
      indicating that the effects of greater tendon stiffness and increased fascicle
      length cancelled out each other. It seems that natural strategies may be in place
      to ensure that the relative operating range of muscle remains unaltered by
      changes in physical activity, in old age.

PMID- 16637870
TI  - Extracellular matrix adaptation of tendon and skeletal muscle to exercise.
AB  - The extracellular matrix (ECM) of connective tissues enables linking to other
      tissues, and plays a key role in force transmission and tissue structure
      maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by
      physical activity, and both collagen synthesis and metalloprotease activity
      increase with mechanical loading. This can be shown by determining propeptide and
      proteinase activity by microdialysis, as well as by verifying the incorporation
      of infused stable isotope amino acids in biopsies. Local tissue expression and
      release of growth factors for ECM such as IGF-1, TGF-beta and IL-6 is enhanced
      following exercise. For tendons, metabolic activity (e.g. detected by positron
      emission tomography scanning), circulatory responses (e.g. as measured by near
      infrared spectroscopy and dye dilution) and collagen turnover are markedly
      increased after exercise. Tendon blood flow is regulated by cyclooxygenase-2 (COX
      2)-mediated pathways, and glucose uptake is regulated by specific pathways in
      tendons that differ from those in skeletal muscle. Chronic loading in the form of
      physical training leads both to increased collagen turnover as well as to some
      degree of net collagen synthesis. These changes modify the mechanical properties
      and the viscoelastic characteristics of the tissue, decrease its stress
      susceptibility and probably make it more load-resistant. The mechanical
      properties of tendon fascicles vary within a given human tendon, and even show
      gender differences. The latter is supported by findings of gender-related
      differences in the activation of collagen synthesis with exercise. These findings
      may provide the basis for understanding tissue overloading and injury in both
      tendons and skeletal muscle.

PMID- 16637871
TI  - How nutrition and exercise maintain the human musculoskeletal mass.
AB  - In this article we review some of our recent work concerning the effects of
      nutrition and exercise on protein synthesis and signal transduction in human
      musculoskeletal tissues. A great deal of new information is being generated by
      the application of recently refined techniques for measuring protein turnover.
      The field remains one that is largely descriptive but increasingly we are
      beginning to discern mechanisms underlying lean tissue maintenance, growth and
      wasting especially as multidisciplinary tools are applied to its study. Several
      types of exercise and nutrition are potent stimuli for protein synthesis in
      skeletal muscle. By contrast, collagen in the extracellular matrix in muscle and
      tendon appears to be mechanically but not nutritionally sensitive. The rates of
      collagen turnover in a variety of tissues are sufficiently high to account for a
      sizeable proportion of whole body protein turnover. One of the most recent
      surprises is the high turnover rate of human bone collagen and its anabolic
      response to feeding. As our understanding of the normal physiology of these
      processes advances, we become better able to construct testable hypotheses
      concerning the effects of ageing and disease on the musculoskeletal mass. Current
      evidence suggests that one of the major problems with loss of muscle during
      ageing is an inability of the tissue to respond adequately to increased
      availability of nutrients.

PMID- 16637872
TI  - The role of neutrophils in injury and repair following muscle stretch.
AB  - Stretch injury to the myotendinous junction is a common problem in competitive
      athletes and those involved in regular physical activity. The major risk factor
      for recurrent injury appears to be the primary injury itself. Physicians,
      physical therapists, athletic trainers and athletes alike continue to search for
      optimal treatment and prevention strategies. Acute inflammation is regarded as
      the body's generalized protective response to tissue injury. An especially
      important and unexplored aspect of inflammation following injury is the role of
      inflammatory cells in extending injury and possibly directing muscle repair. It
      has been suggested that the inflammatory reaction, although it typically
      represents a reaction to damage and necrosis, may even bring about some local
      damage of its own and therefore increase the possibility for scarring and
      fibrosis. Limiting certain aspects of inflammation may theoretically reduce
      muscle damage as well as signals for muscle scarring. Here we focus on the role
      of neutrophils in injury and repair of stretch-injured skeletal muscle. A
      minimally invasive model that generates a reproducible injury to rabbit skeletal
      muscle is presented. We present a plausible theory that neutrophil-derived
      oxidants resulting from the initial stretch injury are responsible for extending
      the damage. An anti-CD11b antibody that blocks the neutrophil's respiratory burst
      is employed to reduce myofibre damage. An intriguing area that is currently being
      explored in our laboratory and others is the potential role for neutrophils to
      contribute to muscle growth and repair. It may be possible that neutrophils
      facilitate muscle repair through removal of tissue debris as well as by
      activation of satellite cells. Recent and ongoing investigations point to
      interleukin-6 as a possible key cytokine in muscle inflammation and repair.
      Studies to elucidate a clearer understanding of this possibility will be
      reviewed.

PMID- 16637873
TI  - Where tendons and ligaments meet bone: attachment sites ('entheses') in relation
      to exercise and/or mechanical load.
AB  - Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions)
      are sites of stress concentration at the region where tendons and ligaments
      attach to bone. Consequently, they are commonly subject to overuse injuries
      (enthesopathies) that are well documented in a number of sports. In this review,
      we focus on the structure-function correlations of entheses on both the hard and
      the soft tissue sides of the junction. Particular attention is paid to mechanical
      factors that influence form and function and thus to exploring the relationship
      between entheses and exercise. The molecular parameters indicative of adaptation
      to mechanical stress are evaluated, and the basis on which entheses are
      classified is explained. The application of the 'enthesis organ' concept (a
      collection of tissues adjacent to the enthesis itself, which jointly serve the
      common function of stress dissipation) to understanding enthesopathies is
      considered and novel roles of adipose tissue at entheses are reviewed. A
      distinction is made between different locations of fat at entheses, and possible
      functions include space-filling and proprioception. The basic anchorage role of
      entheses is considered in detail and comparisons are explored between entheses
      and other biological 'anchorage' sites. The ability of entheses for self-repair
      is emphasized and a range of enthesopathies common in sport are reviewed (e.g.
      tennis elbow, golfer's elbow, jumper's knee, plantar fasciitis and Achilles
      insertional tendinopathies). Attention is drawn to the degenerative, rather than
      inflammatory, nature of most enthesopathies in sport. The biomechanical factors
      contributing to the development of enthesopathies are reviewed and the importance
      of considering the muscle-tendon-bone unit as a whole is recognized. Bony spur
      formation is assessed in relation to other changes at entheses which parallel
      those in osteoarthritic synovial joints.

PMID- 16637874
TI  - The effects of exercise on human articular cartilage.
AB  - The effects of exercise on articular hyaline articular cartilage have
      traditionally been examined in animal models, but until recently little
      information has been available on human cartilage. Magnetic resonance imaging now
      permits cartilage morphology and composition to be analysed quantitatively in
      vivo. This review briefly describes the methodological background of quantitative
      cartilage imaging and summarizes work on short-term (deformational behaviour) and
      long-term (functional adaptation) effects of exercise on human articular
      cartilage. Current findings suggest that human cartilage deforms very little in
      vivo during physiological activities and recovers from deformation within 90 min
      after loading. Whereas cartilage deformation appears to become less with
      increasing age, sex and physical training status do not seem to affect in vivo
      deformational behaviour. There is now good evidence that cartilage undergoes some
      type of atrophy (thinning) under reduced loading conditions, such as with
      postoperative immobilization and paraplegia. However, increased loading (as
      encountered by elite athletes) does not appear to be associated with increased
      average cartilage thickness. Findings in twins, however, suggest a strong genetic
      contribution to cartilage morphology. Potential reasons for the inability of
      cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure
      and a decoupling of mechanical competence and tissue mass.

PMID- 16637875
TI  - The response of bone, articular cartilage and tendon to exercise in the horse.
AB  - Horses can gallop within hours of birth, and may begin training for athletic
      competition while still growing. This review cites studies on the effects of
      exercise on bone, tendon and articular cartilage, as detected by clinical and
      research imaging techniques, tissue biochemical analysis and microscopy of
      various kinds. For bone, alterations in bone mineral content, mineral density and
      the morphology of the mineralized tissue are the most common end-points. Apparent
      bone density increases slightly after athletic training in the cortex, but
      substantially in the major load paths of the epiphyses and cuboidal bones,
      despite the lower material density of the new bone, which is deposited
      subperiosteally and on internal surfaces without prior osteoclastic resorption.
      With training of greater intensity, adaptive change is supervened by patho
      anatomical change in the form of microdamage and frank lesions. In tendon,
      collagen fibril diameter distribution changes significantly during growth, but
      not after early training. The exact amount and type of protracted training that
      does cause reduction in mass average diameter (an early sign of progressive
      microdamage) have not been defined. Training is associated with an increase in
      the cross-sectional area of some tendons, possibly owing to slightly greater
      water content of non-collagenous or newly synthesized matrix. Early training may
      be associated with greater thickness of hyaline but not calcified articular
      cartilage, at least in some sites. The age at which adaptation of cartilage to
      biomechanical influences can occur may thus extend beyond very early life.
      However, cartilage appears to be the most susceptible of the three tissues to
      pathological alteration. The effect of training exercise on the anatomical or
      patho-anatomical features of connective tissue structures is affected by the
      timing, type and amount of natural or imposed exercise during growth and
      development which precedes the training.

PMID- 16637876
TI  - What can studying musicians tell us about motor control of the hand?
AB  - Most standard accounts of human anatomy and physiology are designed to meet the
      requirements of medical education and therefore consider their subject matter
      from the standpoint of typical rather than outstanding levels of performance. To
      understand how high levels of skill are developed and maintained, it is necessary
      to study elite groups such as professional athletes or musicians. This can lead
      to the rediscovery of arcane knowledge that has fallen into neglect through a
      lack of appreciation of its significance. For example, although variability in
      the muscles and tendons of the hand was well known in the nineteenth and early
      twentieth centuries, it is through recent studies of musicians that its practical
      significance has become better appreciated. From even a cursory acquaintance with
      the training methods of sportsmen and women, dancers and musicians, it is clear
      that sophisticated motor skills are developed only at the cost of a great deal of
      time and effort. Over a lifetime of performance, musicians arguably spend more
      time in skill acquisition than almost any other group and offer a number of
      unique advantages for the study of motor control. Such intensive training not
      only modifies cortical maps but may even affect the gross morphology of the
      central nervous system. There is also evidence that in certain individuals this
      process can become maladaptive. Recent studies of musicians suggest that
      intensive training can lead to the appearance of ambiguities in the cortical
      somatosensory representation of the hand that may be associated with the
      development of focal dystonia; a condition to which musicians are particularly
      prone. The realization that changes in cortical maps may underlie dystonia has
      led to the development of new approaches to its treatment, which may ultimately
      benefit musicians and non-musicians alike.

PMID- 16637878
TI  - The amygdaloid complex and the medial and lateral ventricular eminences in staged
      human embryos.
AB  - The amygdaloid complex was investigated in 36 serially sectioned staged human
      embryos, including 20 impregnated with silver. This is the first such account
      based on graphic reconstructions, 28 of which were prepared. Significant findings
      in the human include the following. (1) The medial (first) and (then) lateral
      ventricular eminences arise independently at stages 14 and 15, and unite only at
      stage 18 to form the floor of the lateral ventricle. (2) The future amygdaloid
      region is discernible at stage 14 and the amygdaloid primordium at stage 15. (3)
      The anterior amygdaloid area and the corticomedial and basolateral complexes
      appear at stage 16. (4) These three major divisions arise initially from the
      medial ventricular eminence, which is diencephalic. (5) Individual nuclei begin
      to be detectable at stages 17-21, the central nucleus at stage 23 and the lateral
      nucleus shortly thereafter. (6) The ontogenetic findings in the human embryonic
      period accord best with the classification used by Humphrey. (7) The lateral
      eminence, which is telencephalic, contributes to the cortical nucleus at stage
      18. (8) The primordial plexiform layer develops independently of the cortical
      nucleus. (9) Spatial changes of the nuclei within the amygdaloid complex and of
      the complex as a whole begin in the embryonic period and continue during the
      fetal period, during the early part of which the definitive amygdaloid topography
      in relation to the corpus striatum is attained. (10) The developing amygdaloid
      nuclei are closely related to the medial forebrain bundle, which has already
      appeared in stage 15. (11) Fibre connections develop successively between the
      amygdaloid nuclei and the septal, hippocampal and diencephalic formations,
      constituting the beginning of the limbic system before the end of the embryonic
      period. Although the nucleus accumbens also appears relatively early (stage 19),
      connections between it and the amygdaloid complex are not evident during the
      embryonic period. (12) Influence of the olfactory bulb and tubercle on initial
      amygdaloid development, as postulated for rodents, is unlikely in the human. The
      findings exemplify the necessity of beginning developmental studies with the
      embryonic period proper.

PMID- 16637879
TI  - Ultrastructural features of neurons and synaptic contacts in the posterodorsal
      medial amygdala of adult male rats.
AB  - The aim of the present study was to describe the ultrastructure of neurons (from
      eight animals) and to analyse the synaptic terminal distribution (from two
      animals) in the posterodorsal subnucleus of the medial amygdala (MePD) of adult
      male rats. Using transmission electron microscopy, it was possible to identify
      many spiny and aspiny dendrites, unmyelinated axonal bundles, single axonal
      processes, a few myelinated axons, blood vessels and glial processes in the
      neuropil. Axodendritic synapses were the most frequently observed (67.5%),
      appearing to be of either the inhibitory or the excitatory types. The presynaptic
      region contained round or flattened vesicles that occurred either singly or with
      dense-cored vesicles (DCVs). The dendrites often received many synapses on a
      single shaft, and axon terminals displayed synaptic contacts with one or more
      postsynaptic structures. Dendritic spines showed different morphologies and the
      synapses on them (23.1%) formed a single and apparently excitatory synaptic
      contact with round, electron-lucid vesicles alone or, less frequently, with DCVs.
      Inhibitory and excitatory axosomatic synapses (8.2%) and excitatory axoaxonic
      synapses (1.2%) were also identified. The present report provides new findings
      relevant to the study of the MePD cellular organization and could be combined
      with other morphological data in order to reveal the functional activity of this
      area in male rats.

PMID- 16637880
TI  - Total number of neurons in the habenular nuclei of the rat epithalamus: a
      stereological study.
AB  - The total number of neurons in the medial and lateral habenular nuclei of the rat
      epithalamus was estimated using modern stereological counting methods and
      systematic random sampling techniques. Six to eight young adult male rats, and a
      complete set of serial 40-microm glycolmethacrylate sections for each rat, were
      used to quantify neuronal numbers. After a random start, a systematic subset
      (e.g. every third) of the serial sections was used to estimate the total volume
      of each nucleus using Cavalieri's method. The same set of sampled sections was
      used to estimate the number of neurons in a known subvolume (i.e. the numerical
      density N(v)) by the optical disector method. Multiplication of the total volume
      by N(v) yielded the total number of neurons. It was found that the right medial
      habenular nucleus consisted, on average, of 18,000 neurons (with a coefficient of
      variation of 0.18), while the right lateral habenular nucleus had 13,000 neurons
      on average (0.14). These total neuronal numbers provide important data for the
      transfer of information through these nuclei and for species comparisons.

PMID- 16637881
TI  - Vascularization of rat pituitary autografts.
AB  - Pituitary autotransplantation eliminates direct vascular contact between the
      hypothalamus and the adenohypophysis, and enables us to study the role of the
      hypothalamus in regulating adenohypophysial endocrine activity. The aim of this
      study was to investigate vascularization of the pituitary autografts. Three-month
      old male Wistar rats were hypophysectomized, and their adenohypophyses were
      autotransplanted under the renal capsule. The animals were killed 3 weeks after
      autotransplantation. The grafts were removed and studied by using histology,
      immunohistochemistry and transmission electron microscopy. In the central portion
      of the grafts, organizing necrosis was apparent. The peripheral portion of the
      graft contained all adenohypophysial cell types, with a predominance of
      lactotrophs. Vascular endothelial growth factor and hypoxia-inducible factor were
      expressed in the graft mainly in the perinecrotic areas. Several capillaries
      inside the grafts were lined by continuous unfenestrated epithelium, while others
      were lined by fenestrated endothelium, suggesting that neovascularization is the
      result of two processes: ingrowths of capillaries from the renal capsule to the
      graft, and neoformation of capillaries from pre-existing adenohypophysial
      vessels. In conclusion, hypoxia seems to be an important factor in the
      vascularization of pituitary autografts. Mediated via hypoxia-inducible factor,
      hypoxia stimulates vascular endothelial growth factor secretion, which plays a
      crucial role in angiogenesis.

PMID- 16637882
TI  - Subcellular localization of epidermal growth factor receptor in human
      submandibular gland.
AB  - The subcellular distribution of the epidermal growth factor receptor (EGFr) was
      demonstrated in the normal human submandibular gland by means of immunogold
      cytochemistry. EGFr labelling appeared in both acinar and ductal cells, where
      strong immunoreactivity was associated with a tubulovesicular system near the
      basolateral surfaces. In addition, groups of reactive vesicles were highlighted
      among secretory granules of both serous and mucous cells and at the apex of
      ductal cells. Basolateral vesicles were interpreted as being a result of EGFr
      internalization after activation by an exogenous ligand, although the functional
      meaning of those located apically remains unclear.

PMID- 16637883
TI  - An anatomical study of the buccinator muscle fibres that extend to the terminal
      portion of the parotid duct, and their functional roles in salivary secretion.
AB  - Until now there has been no definitive anatomical study describing the area where
      the parotid duct enters the buccinator muscle. In this study, we performed
      anatomical and histological examinations to investigate the relationship between
      the parotid duct and the buccinator muscle. Thirty specimens (including the
      buccinator and the terminal portion of the parotid duct) were obtained from
      embalmed Korean cadavers. Dissection was performed on 22 of these specimens, and
      the remaining eight specimens were prepared for histological examination and
      stained with haematoxylin-eosin or Gomori trichrome. In all specimens, small,
      distinct muscle fibres originating from the buccinator muscle extended to and
      inserted into the terminal portion of the parotid duct. The topography of these
      fibres varied, and we classified them into three categories according to where
      they originated. Type I buccinator muscle fibres, which inserted into the
      terminal portion of the parotid duct, originated simultaneously from the anterior
      and posterior aspects of the duct (ten cases, 45.5%). Type II fibres originated
      from the anterior aspect of the duct and inserted into the anterior side of the
      duct (seven cases, 31.8%). Type III fibres originated from the posterior aspect
      of the parotid duct and ran anteriorly toward the duct (five cases, 22.7%). These
      results were confirmed in the histological examination of all eight specimens.
      Based on these findings, we have proposed a tentative description of the
      physiological role of the buccinator muscle fibres in salivary secretion and in
      the formation of the sialoliths.

PMID- 16637884
TI  - Antimicrobial defence mechanisms of the human parotid duct.
AB  - The parotid duct transports saliva from the gland into the oral cavity. However,
      its immune response properties, along with the secretion and moistening
      principles of the duct, have not yet been fully investigated. These properties
      may play an important role in protecting the parotid gland from infection and
      also prevent development of sialodocholithiasis, as the parotid duct -- in
      contrast to the submandibular salivary duct -- is often free of duct concrements.
      Up to now, only the parotid gland has been investigated, without regard to its
      duct. The present study analyses the structures of the parotid duct in their
      relations to antimicrobial defence mechanisms and rheological properties.
      Investigations were performed on 23 parotid ducts using histological,
      histochemical and immunohistochemical methods. Epithelial and goblet cells of the
      parotid duct synthesize a complex mucous layer that covers the epithelium. The
      viscosity is influenced by secreted mucins and TFF peptides. This layer contains
      carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose,
      mannose, fucose and sialic acids. The lamina propria contains granulocytes, T
      lymphocytes and macrophages. IgA, produced by plasma cells in the subepithelial
      layer, is frequently integrated in the secretory product. Synthesized mucins, TFF
      peptides, carbohydrates and immunoglobulins form a complex layer that can be
      expected to prohibit infection and enables salivary flow. Our study demonstrates
      that the steady secretion of the parotid gland, together with the ductal cellular
      and biochemical immune protection system, is likely to thwart ascending
      infections in the parotid duct and gland.

PMID- 16637885
TI  - Cell structure of developing downfeathers in the zebrafinch with emphasis on barb
      ridge morphogenesis.
AB  - The present ultrastructural and immunocytochemical study on the embryonic
      feathers of the zebrafinch, an altricial passerine bird, describes cellular
      differentiation of developing downfeathers. Barb ridges are folds of the original
      epidermis of the embryonic feather germ in which the basal-apical polarity of
      epidermal cells is upset. The result is the loss of most germinal activity of
      basal cells of the barb ridges so that only the embryonic epidermal layers
      remain. The more external layer is the primary periderm, followed by 4-6 layers
      of inner-periderm cells that mature into feather sheath and barb vane ridge
      cells. The following layer, the subperiderm, produces a small type of beta
      keratin typical of feathers. In barb ridges, the subperiderm layer is displaced
      to form barbule plates and barb cells. The formation of branching barbules occurs
      by the presence of barb vane ridge cells that function as spacers between barbule
      cells. The fourth layer is homologous to the germinal layer of the epidermis, but
      in barb ridges it rapidly loses the germinal capability and becomes the
      cyclindrical layer of marginal plates. The study indicates that a necrotic
      process determines the carving out of the final feather shape, although apoptosis
      may also play a role. In fact, after barb and barbule cells have formed a
      keratinized syncitium, retraction of the vascular bed determines anoxia with the
      resultant necrosis of all feather cells. Only those of the keratinized syncitium
      remain to form the feather while supportive cells disappear. The sheath covering
      the barb and barbule syncitium is lost by the formation of a sloughing layer
      following degeneration of external barb ridge vane cells and loss of the sheath.
      It is proposed that the evolution of the morphogenetic process of barb ridge
      formation was peculiar to tubular outgrowths of the integument of archosaurian
      reptiles that evolved into birds. Once established in the embryonic programmes of
      skin morphogenesis of ancient birds, variations in the process of barb ridge
      morphogenesis allowed the fusion of ridges into large or branched ridges that
      originated the rachis. This process produced pennaceous feathers, among which
      were those later used for flight. The present study stresses that the
      morphogenetic process of barb ridge formation determines the concomitant
      appearance of barbs and barbules. As a consequence, intermediate forms of
      evolving feathers with only barbs but not barbules are unlikely or are derived
      from alteration of the above basic morphogenetic mechanism.

PMID- 16637886
TI  - A new model for the morphology of the arrector pili muscle in the follicular unit
      based on three-dimensional reconstruction.
AB  - In the classic model of the arrector pili (AP) muscle, each hair follicle is
      independently associated with a single AP muscle. Recently, new models have been
      proposed based on interpretations of serial histological cross-sectional images.
      The purpose of this study was to confirm the morphology of the AP muscle in
      relation to the follicular unit (FU) using quantitative three-dimensional (3D)
      reconstruction of serially sectioned images. Skin samples were obtained from the
      parietal region of the scalp, and processed using routine histological
      procedures. The serially sectioned slides were stained with Masson's trichrome.
      All the hairs and hair follicles of the FU exhibited some degree of slanting,
      with the single AP muscle slanted in the same direction. The distal portion of
      the AP muscle was divided into branches, as in a bronchial tree. There was
      branching in the single AP muscle present in the FU, and it was inserted into all
      the hair follicles of the FU either tightly or loosely. We suggest that the
      classic anatomy of the AP muscle must be modified with this new model, now
      confirmed by computer-based 3D reconstruction.

PMID- 16637887
TI  - Origin of the styloglossus muscle in the human fetus.
AB  - The origin of the styloglossus muscle was histologically studied bilaterally in
      nine human fetuses (18 sides). In all cases, the muscle originated in Reichert's
      cartilage, which gives rise to the temporal styloid process. We identified three
      types of variation: type A, an accessory muscle fascicle originating from the
      mandibular angle, found in 7 cases (12 sides); type B, where the styloglossus
      muscle was attached to the mandibular angle by fibrous tracts, found in three
      cases (4 sides); and type C, where an accessory muscle fascicle arose from the
      fibrous tract connecting Reichert's cartilage to the mandibular angle; found in
      one case. In all cases (2 sides), the styloglossus muscle was innervated by the
      hypoglossal nerve. Relationships between the styloglossus muscle and
      vasculonervous elements of the prestyloid and retrostyloid spaces were analysed.

PMID- 16637889
TI  - The high-affinity immunoglobulin-E receptor (FcepsilonRI) is endocytosed by an AP
      2/clathrin-independent, dynamin-dependent mechanism.
AB  - Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcepsilonRI),
      expressed on mast cells and basophils, initiates the immediate hypersensitivity
      reaction. Aggregated FcepsilonRI has been reported to rapidly migrate to lipid
      rafts in RBL-2H3 cells. We confirmed that aggregated FcepsilonRI is found in the
      lipid raft fractions of cellular lysates. Furthermore, we show that the cross
      linked FcepsilonRI remains associated with detergent-resistant structures upon
      internalization. Previous morphological studies have reported that aggregated
      FepsiloncRI is endocytosed via clathrin-coated pits, which in general are not
      lipid raft associated. To address this apparent discrepancy, we employed siRNA to
      suppress expression of components of the clathrin-mediated internalization
      machinery, namely, clathrin heavy chain, and the AP-2 (alpha-adaptin or mu2
      subunit). Transferrin receptor (TfR) is endocytosed by a clathrin-mediated
      process and, as expected, each transfected siRNA caused a two to threefold
      elevation of TfR surface expression and almost completely inhibited its
      endocytosis. In contrast, there was no effect on surface expression levels of
      FcepsilonRI nor on the endocytosis of the dinitrophenyl-human serum albumin (DNP
      HSA)/IgE/FcepsilonRI complex. On the contrary, internalization of DNP
      HSA/IgE/FcepsilonRI was inhibited by overexpression of a dominant-negative
      dynamin mutant. We conclude that internalization of cross-linked FcRI does not
      require the AP-2/clathrin complex but is dynamin-dependent and may be lipid raft
      mediated.

PMID- 16637890
TI  - Intracellular Salmonella enterica redirect exocytic transport processes in a
      Salmonella pathogenicity island 2-dependent manner.
AB  - During intracellular life, Salmonella enterica proliferate within a specialized
      membrane compartment, the Salmonella-containing vacuole (SCV), and interfere with
      the microtubule cytoskeleton and cellular transport. To characterize the
      interaction of intracellular Salmonella with host cell transport processes, we
      utilized various model systems to follow microtubule-dependent transport. The
      vesicular stomatitis virus glycoprotein (VSVG) is a commonly used marker to
      follow protein transport from the Golgi to the plasma membrane. Using a VSVG-GFP
      fusion protein, we observed that virulent intracellular Salmonella alter
      exocytotic transport and recruit exocytotic transport vesicles to the SCV. This
      virulence function was dependent on the function of the type III secretion system
      encoded by Salmonella Pathogenicity Island 2 (SPI2) and more specifically on a
      subset of SPI2 effector proteins. Furthermore, the Golgi to plasma membrane
      traffic of the shingolipid C(5)-ceramide was redirected to the SCV by virulent
      Salmonella. We propose that Salmonella modulates the biogenesis of the SCV by
      deviating this compartment from the default endocytic pathway to an organelle
      that interacts with the exocytic pathway. This observation might reveal a novel
      element of the intracellular survival and replication strategy of Salmonella.

PMID- 16637891
TI  - Steady state analysis and experimental validation of a model for hepatic high
      density lipoprotein transport.
AB  - Transport of high-density lipoprotein (HDL) in the hepatocyte plays a fundamental
      role in reverse cholesterol transport and regulation of plasma HDL levels. On the
      basis of a recently developed kinetic model, the steady state distribution of HDL
      was analyzed. Fractional fluorescence of labeled HDL in the basolateral membrane,
      sorting endosomes (SE), the subapical compartment/ apical recycling compartment,
      the biliary canaliculus and in late endosomes and lysosomes (LE/LYS) including
      expected standard deviation is predicted. Improved parameter estimation was
      obtained by including kinetic data of apical endocytosis of fluorescent markers
      for LE/LYS, asialoorosomucoid and Rhodamine-dextran, in the regression. Predicted
      values using the refined kinetic parameters are in good agreement with
      experimental values of compartmental steady state fluorescence of Alexa488-HDL in
      polarized hepatic HepG2 cells. From calculated steady state fluxes, it is
      suggested that export of HDL from basolateral SE is the key step for determining
      the transport of HDL through the hepatocyte. The analysis provides testable
      predictions for high-throughput fluorescence microscopy screening experiments on
      potential inhibitors of hepatic HDL processing. By quantitative fluorescence
      imaging and model analysis, it is shown that the phosphoinositide kinase
      inhibitor wortmannin prevents apical transport of fluorescent HDL from
      basolateral SE. The results support that endosomes of polarized hepatic cells
      have different sorting functions and that apical endocytosis is an integrative
      trafficking step in hepatocytes.

PMID- 16637892
TI  - Scientists share nuclear secrets at Jekyll Island.

PMID- 16637893
TI  - How can we make our medical students enthusiastic about a future in obstetrics
      and gynaecology?
AB  - Falling recruitment to obstetrics and gynaecology (O&G) among UK-trained
      undergraduates is a pressing concern. The reasons for this are multifactorial and
      include the previous restriction on the number of postgraduate training places.
      Undergraduate placements are a key time to encourage potential recruits into the
      specialty. A recent survey demonstrated various changes within medical school
      attachments over the past 15 years that are having a mixed influence on the
      undergraduate O&G experience. These are explored in relation to their potential
      impact on recruitment.

PMID- 16637894
TI  - Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness
      of initial diagnostic strategies.
AB  - OBJECTIVE: To determine the most cost-effective outpatient testing strategy for
      diagnosing endometrial cancer in women with postmenopausal bleeding (PMB).
      DESIGN: Decision analysis modelling. POPULATION: Women with postmenopausal
      bleeding. METHODS: A decision analytic model was constructed to reflect current
      service provision, which evaluated 12 diagnostic strategies using endometrial
      biopsy (EB), ultrasonography (USS) (4- and 5-mm endometrial thickness cutoff) and
      hysteroscopy. Diagnostic probability estimates were derived from systematic
      quantitative reviews, clinical outcomes from published literature and cost
      estimates from local and NHS sources. MAIN OUTCOME MEASURES: The cost per
      additional life year gained (pound/LYG) was determined and compared for each
      diagnostic strategy, and sensitivity analyses were performed. RESULTS: Compared
      with carrying out no initial investigation, a strategy based on initial diagnosis
      with USS using a 5-mm cutoff was the least expensive (11,470 pound/LYG). Initial
      investigation with EB or USS using a 4-mm cutoff was comparably cost-effective
      (less than 30,000 pound/LYG versus USS with a 5-mm cutoff) at their most
      favourable diagnostic performance and at disease prevalence of 10% or more. The
      strategies involving initial evaluation with test combinations or hysteroscopy
      alone were not cost-effective. CONCLUSIONS: Women presenting for the first time
      with PMB should undergo initial evaluation with USS or EB.

PMID- 16637895
TI  - Association of phthalate esters with endometriosis in Indian women.
AB  - OBJECTIVE: To evaluate the possible association between phthalate esters (PEs)
      and the occurrence of endometriosis. DESIGN: Case-control study. SETTING:
      Department of Reproductive Medicine, Bhagawan Mahavir Medical Research Centre,
      Maternal Health and Reproductive Institute and Department of Analytical R&D,
      Hetero Research Foundation, Hyderabad, Andhra Pradesh, India. SAMPLE: Blood
      samples were collected from 49 infertile women with endometriosis (study group);
      38 age-matched women without endometriosis (control group I) but with infertility
      related to tubal defects, fibroids, polycystic ovaries, idiopathic infertility
      and pelvic inflammatory diseases diagnosed by laparoscopy and a further group of
      21 age-matched women (control group II) with proven fertility and no evidence of
      endometriosis and other gynaecological disorders during laparoscopic
      sterilisation. METHODS: Concentrations of PEs were measured using gas
      chromatography. MAIN OUTCOME MEASURES: Evaluation of PEs concentrations in women
      with endometriosis compared with women free from the disease. RESULTS: Women with
      endometriosis showed significantly higher concentrations of di-n-butyl phthalate
      (DnBP), butyl benzyl phthalate (BBP), di-n-octyl phthalate (DnOP) and diethyl
      hexyl phthalate (DEHP) (mean 0.44 [SD 0.41]; 0.66 [SD 0.61]; 3.32 [SD 2.17]; 2.44
      [SD 2.17] micrograms/ml) compared with control group I (mean 0.08 [SD 0.14]; 0.12
      [SD 0.20]; 0; 0.50 [SD 0.80] micrograms/ml) and control group II (mean 0.15 [SD
      0.21]; 0.11 [SD 0.22]; 0; 0.45 [SD 0.68] micrograms/ml). The correlation between
      the concentrations of PEs and different severity of endometriosis was strong and
      statistically significant at P < 0.05 for all four compounds (DnBP: r=+0.73, P <
      0.0001; BBP: r=+0.78, P < 0.0001; DnOP: r=+0.57, P < 0.0001 and DEHP: r=+0.44, P
      < 0.0014). CONCLUSIONS: This study suggests that PEs may have an aetiological
      association with endometriosis.

PMID- 16637896
TI  - Failing pregnancies of unknown location: a prospective evaluation of the human
      chorionic gonadotrophin ratio.
AB  - OBJECTIVE: To assess the performance of the human chorionic gonadotrophin (hCG)
      ratio (hCG 48 hours/hCG 0 hour) to predict spontaneous resolution of pregnancies
      of unknown location (PUL). DESIGN: Prospective cohort study. SETTING: Teaching
      Hospital Early Pregnancy Unit. POPULATION: Women classified as having a PUL.
      METHODS: The optimal cutoff value for hCG ratio (serum hCG at 48 hours/serum hCG
      at 0 hours) was calculated from data on 189 consecutive PULs (the 'training
      set'). This cutoff was tested prospectively on a further 200 consecutive PULs
      (the 'test set'). The hCG ratio was also compared to absolute levels of serum hCG
      at 0 and 48 hour for the prediction of failing PULs. MAIN OUTCOME MEASURES: hCG
      ratio in spontaneously resolving ('failing') PUL compared with those requiring
      intervention. Optimum cutoff determined and tested to predict spontaneously
      resolving PUL. Comparison of hCG ratio with absolute levels of serum hCG.
      RESULTS: A total of 3996 consecutive women were scanned, of which 438 (11.0%)
      were classified as PULs. Complete data were available for 389 women: 189 in the
      training set and 200 in the test set. In the training set, there were 102 (54%)
      failing PUL, while 109 (55%) in the test set. hCG ratio of <0.87 predicted
      failing PUL, with a sensitivity of 93.1% (95% CI 85.9-97.0) and a specificity of
      90.8% (95% CI 82.2-95.7) in the training set. In the test set, sensitivity was
      92.7% (95% CI 85.6-96.5) and specificity was 96.7% (95% CI 90.0-99.1). The hCG
      ratio outperformed absolute serum hCG levels at 0 and 48 hours. CONCLUSIONS: We
      have defined the optimal hCG ratio for the prediction of failing PUL. Using this
      cutoff, clinicians can safely adopt a noninterventional approach in women with
      PUL.

PMID- 16637897
TI  - Preterm birth and multiple pregnancy in European countries participating in the
      PERISTAT project.
AB  - OBJECTIVE: To compare rates of preterm birth among multiple births in European
      countries, to estimate their contribution to overall preterm birth rates and to
      explore factors which could explain differences between preterm birth rates.
      DESIGN: Analyses of data from vital statistics, birth registers or national
      samples of births. SETTING: Eleven member states of the European Union.
      POPULATION: All live births or representative samples of births at national or
      regional level for the year 2000 or most recent year. METHODS: Description of
      rates of preterm birth before 37 and 32 weeks, estimation of population
      attributable risks (PAR), study of associations between preterm birth rates in
      multiples and singletons and nonspontaneous labour using Spearman's rank
      correlation coefficient. MAIN OUTCOME MEASURES: Preterm birth rates, PAR,
      proportions of deliveries with nonspontaneous onset (caesarean sections before
      labour or induction of labour). RESULTS: The proportion of multiple births before
      37 weeks varied from 68.4% in Austria to 42.2% in the Republic of Ireland. In
      half of the countries, over 20% of all preterm births were attributable to
      multiple births. A strong association was found between the proportions of births
      before 37 weeks among multiple and singleton births (r= 0.81; P < 0.001). An
      association was observed between the rates of preterm birth and the proportions
      of deliveries with nonspontaneous onset among twins. CONCLUSIONS: Wide variations
      in rates of preterm births and deliveries with nonspontaneous onset were found
      between countries, suggesting marked differences in clinical practice which could
      have long-term implications for the health of children from multiple births.

PMID- 16637898
TI  - Genes encoding bile acid, phospholipid and anion transporters are expressed in a
      human fetal cardiomyocyte culture.
AB  - OBJECTIVES: To establish a human fetal cardiomyocyte culture and to investigate
      whether the genes that encode transporters that may influence influx or efflux of
      bile acids are expressed in human fetal cardiomyocytes. DESIGN: Laboratory study.
      SETTING: Imperial College London. SAMPLE: Six fetal hearts were obtained at the
      time of termination of pregnancy at 12-13 weeks of gestation and used to generate
      primary human cardiomyocyte cultures. METHODS: To confirm the presence of
      cardiomyocytes, the cells were incubated with monoclonal antibodies to sarcomeric
      alpha-actinin and anticardiac myosin heavy chain. Real-time reverse transcription
      polymerase chain reaction was used to establish whether transcripts of genes that
      may influence bile acid transport are present in the culture (NTCP, BSEP, MDR3,
      FIC1, MRP2, MRP3, OATP-A, OATP-C, OATP-D, OATP-E) and whether taurocholate
      administration alters messenger RNA (mRNA) expression. MAIN OUTCOME MEASURES:
      Relative mRNA expression of genes of interest. RESULTS: Real-time polymerase
      chain reaction demonstrated the presence of mRNA for BSEP, MDR3, FIC1, OATP-C,
      OATP-D and OATP-E in fetal heart. Four transcripts remained in the cardiomyocyte
      culture (BSEP, MDR3, FIC1 and OATP-D), and we demonstrated the influence of
      taurocholate on gene expression. CONCLUSIONS: We have developed an in vitro model
      of the fetal heart that may be used for studies of the cardiac effect of
      endobiotics, e.g. bile acids, or of specific agents that may be used to treat the
      mother or fetus in pregnancy.

PMID- 16637899
TI  - Drug prescription patterns before, during and after pregnancy for chronic,
      occasional and pregnancy-related drugs in the Netherlands.
AB  - OBJECTIVE: To compare the prescription of drugs in women over a period from 2
      years before until 3 months after pregnancy, regarding the type of drugs used and
      the fetal risk. DESIGN: A cohort study based on pharmacy records of women giving
      birth to a child between 1994 and 2003. SETTING: The study was performed with
      data from the InterAction database, containing prescription-drug-dispensing data
      from community pharmacies. POPULATION: The study population included 5412 women
      for whom complete pharmacy records were available. METHODS: Drugs were classified
      into three categories: (1) drugs for chronic conditions, (2) drugs for occasional
      use and (3) drugs for pregnancy-related symptoms and also classified according to
      the Australian classification system. MAIN OUTCOME MEASURES: The prescription
      rate was calculated as the number of women per 100 women who received one or more
      prescriptions for a given drug within a specified time period. RESULTS: About
      79.1% of the women received at least one prescription during pregnancy. The
      prescription rate for most drugs for chronic diseases and for occasional use
      decreased during pregnancy, whereas, as expected, the prescription rate for
      pregnancy-related drugs increased. During the first trimester of pregnancy, 1.7%
      of all drugs prescribed for chronic conditions and 2.3% of the occasional drugs
      were classified as harmful. CONCLUSIONS: The increase in prescription rate during
      pregnancy is caused by an increase in prescription rate of drugs for pregnancy
      related symptoms. The prescription of harmful drugs is more commonly associated
      with drugs for occasional use rather than with drugs for chronic conditions.
      Therefore, a more cautious prescribing of drugs to healthy women in the fertile
      age is necessary.

PMID- 16637900
TI  - Increased serum phosphodiesterase activity in women with pre-eclampsia.
AB  - OBJECTIVE: To measure the activity of serum phosphodiesterase (PDE) in pre
      eclampsia. DESIGN: Case-control study. SETTING: Nephrology Laboratory and
      Obstetrics Unit at Sao Lucas Hospital from Pontificia Universidade Catolica do
      Rio Grande do Sul, Porto Alegre, Brazil. SAMPLE: Twenty-nine normal and 28
      pregnant women with pre-eclampsia. METHODS: Serum was collected from women with
      pre-eclampsia, at the time of diagnosis, and from gestation-matched controls.
      Circulating PDE activity was assessed by measuring consumption of the substrate
      thymidine 5'-monophosphate p-nitrophenyl ester and expressed as PDE units/l. MAIN
      OUTCOME MEASURES: Serum PDE Activity. RESULTS: Mean substrate consumption was
      higher in pre-eclamptic condition (V(max)= 15.8 +/- 1.4 versus 12.7 +/- 0.9 U/L,
      P= 3.7 x 10(-14)). CONCLUSION: These data suggest that altered PDE activity may
      play a role in pre-eclampsia endothelial dysfunction.

PMID- 16637901
TI  - Laser Doppler perfusion imaging: a method for measuring female sexual response.
AB  - To develop a new noninvasive technique to measure vulval blood flow changes
      during sexual arousal; 18 healthy volunteers between the age of 20 and 33 years
      were studied. Each subject underwent two experimental sessions at least 2 weeks
      apart to coincide with the proliferative and luteal phases of her menstrual
      cycle. An initial laser Doppler perfusion imaging (LDPI) scan of the vulva was
      performed. The subject was then given a chapter of erotic fiction to read and a
      repeat LDPI scan was performed immediately after. The percentage change in flux
      were calculated: the clitoral skin blood flow increased by 26.4% (P < 0.05),
      labial skin blood flow by 24.9% (P < 0.05) and the posterior fourchette skin
      blood flow by 35.3% (P < 0.05). LDPI can detect changes in vulval perfusion
      during the sexual arousal response and could be used to compare healthy subjects
      with female sexual dysfunction patients, as well as for assessing the benefits of
      any treatment for this condition.

PMID- 16637902
TI  - High myopia and pre-eclampsia: a blinding combination.

PMID- 16637903
TI  - Laparoscopic sclerotherapy in a case of pelvic congestion syndrome.

PMID- 16637904
TI  - Where is the evidence to screen for gestational diabetes?

PMID- 16637905
TI  - Does exposure to di(2-ethylhexyl) phthalate in pre-pubertal boars affect semen
      quality post-puberty?
AB  - Di(2-ethylhexyl) phthalate (DEHP), a plastic softener used in polyvinyl chloride
      (PVC) products, has been ascribed to have toxic effects on animal reproduction.
      The present study aimed at determining potential late effects of pre-pubertal
      oral exposure to DEHP on semen quality in young pigs. Ten pairs of cross-bred
      male siblings were used. One brother in each pair became, at random, the test
      animal while the other acted as control. Test males were exposed to 300 mg/kg
      body weight (bw) of DEHP administered orally three times a week from 3 to 7 weeks
      of age. The control group was given placebo (water). Semen analyses started when
      the boars reached 6 months of age, with semen collected twice weekly, until
      animals were 9 months of age. Semen was evaluated for ejaculate volume, sperm
      concentration, total sperm count, sperm motility, sperm morphology (including
      presence of cells other than spermatozoa) and sperm plasma membrane integrity.
      Total sperm motility tended to be lower while local motility was higher in the
      DEHP-exposed group compared with controls (p = 0.07) when assessed by computer
      assisted sperm analysis. The DEHP-exposed group had a significantly (p < 0.05)
      lower percentage of spermatozoa with tailless, defective heads (at 7-8 months of
      age) and double-folded tails (at 6-7, 7-8 and 6-9 months of age), compared with
      controls (albeit always under 5%). In summary, there were no obvious adverse
      effects of early oral exposure to 300 mg/kg bw of DEHP on sperm output and sperm
      quality in post-pubertal young boars.

PMID- 16637906
TI  - Effects of extracts of miswak and derum on proliferation of Balb/C 3T3
      fibroblasts and viability of cariogenic bacteria.
AB  - OBJECTIVES: This study examined the effects of extracts of two chewing sticks on
      proliferation of fibroblasts and viability of cariogenic bacteria. METHODS:
      Aqueous extracts of miswak (Salvadora persica; Arak tree) and derum (Juglans
      regia; walnut tree) were prepared and their effects investigated on growth of
      Balb/C 3T3 mouse fibroblasts by measuring the mitochondrial succinic
      dehydrogenase activity. Furthermore, the effects on the viability of various
      cariogenic bacteria (Streptococcus mutans, Streptococcus salivarius,
      Lactobacillus casei and Actinomyces viscosus) was also determined. RESULTS: The
      data revealed that Balb/C 3T3 fibroblasts exposed to aqueous extracts of miswak
      or derum showed an increase in cell proliferation by 156% and 255%, respectively,
      in comparison with controls (p < 0.0001). Furthermore, extracts from both miswak
      and derum had adverse effects on the growth of the cariogenic microorganisms,
      with derum having significantly greater antimicrobial effects than miswak and at
      much lower concentrations against all the bacteria tested. The most sensitive
      organisms were A. viscosus, followed by S. mutans, S. salivarius, with L. casei
      being the most resistant. CONCLUSION: The results show that aqueous extracts of
      miswak and derum enhance the growth of fibroblasts and inhibit the growth of
      cariogenic bacteria, with the derum extract showing greater activity than miswak.

PMID- 16637907
TI  - Oral health status in individuals with dementia living in special facilities.
AB  - AIM: The aim of this review was to retrieve data describing the oral health
      status of individuals with dementia living in special facilities. MATERIALS AND
      METHODS: A literature search on the MEDLINE database (Entrez PubMed) was
      performed. The literature search yielded 208 papers, of which seven publications
      were selected for evaluation. RESULTS: From the available studies poorer oral
      hygiene, decreased saliva flow rates and a higher caries incidence were reported
      in individuals with dementia living in special facilities when compared with
      healthy individuals. Oral health problems were more pronounced in the severe
      stage of the disease. CONCLUSIONS: There is limited scientific data describing
      the oral health status of individuals with dementia living in special facilities.
      However, available data indicate that individuals with dementia living in special
      facilities have more oral health problems than individuals without dementia.

PMID- 16637908
TI  - Oral health status of vulnerable groups in a village of the Central Highlands,
      southern Vietnam.
AB  - OBJECTIVES: Oral health status of vulnerable people in developing countries tends
      to be given lower priority than other health issues. Consequently, few studies
      have examined the oral health status of the poor and minorities in developing
      countries. We aim to examine the dental caries and periodontal status, and
      explore the risk indicators of dental caries between two ethnic groups in rural
      villages in southern Vietnam. METHODS: We examined the caries status and its risk
      indicators of 150 participants (Co-Ho minority and Kinh majority) living in a
      hamlet of Dangphuong village in Vietnam. We also assessed periodontal status of
      the participants aged 14 and over by Community Periodontal Index. RESULTS: We
      first found that dental caries were highly prevalent among both the Co-Ho
      minority and Kinh majority groups. Second, the higher numbers of dental caries
      among children with primary teeth were associated with a higher frequency of
      consuming sweets. Third, most people (87%) aged 14 and over had periodontal
      problems. Finally, the Kinh majority tended to have more dental caries than Co-Ho
      among people aged less than 30. CONCLUSION: Oral health promotion should be
      considered as a part of the development programmes for vulnerable groups in
      Vietnam and other developing countries.

PMID- 16637909
TI  - Improved compliance and self-care in patients with periodontitis--a randomized
      control trial.
AB  - The present study was a randomized control trial to test an intervention
      emanating from the Client Self-care Commitment Model (CSCCM), to encourage
      patients to increase their responsibility for their oral self-care. MATERIALS AND
      METHODS: A total of 75 individuals were re-examined 1-2 years after their initial
      therapy at the Department of Periodontology, Uppsala County Council, Sweden.
      Patients who exhibited insufficient compliance, 37 individuals, were included in
      a randomized single-blind control trial to test an intervention based on the
      CSCCM. Patients were examined at baseline and 3 months after hygiene treatment.
      RESULTS: The results demonstrated that patients in the intervention (IV) group
      increased their interdental cleaning and reduced their plaque index significantly
      compared with the control group. The former also reduced the number of
      periodontal pockets >4 mm significantly from baseline until after the hygiene
      treatment. The majority of the individuals in the IV group reported that the
      written commitment had influenced on their oral self-care habits in a positive
      direction. CONCLUSIONS: The CSCCM enhanced the client participation in the
      treatment process and improved the compliance and oral self-care behaviours. In
      addition, the model contributed to a reduction in periodontal pockets.

PMID- 16637910
TI  - Non-surgical treatment of peri-implant pathology.
AB  - INTRODUCTION: Peri-implant pathologies consist of an inflammatory process
      affecting the soft and hard tissues surrounding the implants. Chlorhexidine is
      considered the gold standard antiseptic, with a large variety of choice in
      administration. In this study, a protocol for the irrigation of peri-implant
      pockets with a chlorhexidine gel, using a plastic needle for the delivery of the
      product into the peri-implant pockets is described. STUDY PARTICIPANTS AND
      METHODS: Nine patients with at least one implant presenting peri-implant
      pathology (inflamed soft tissue associated with bone loss around the implant)
      were enrolled in this prospective clinical study, and followed-up for 1 year,
      where clinical parameters such as modified plaque index, modified bleeding index,
      probing pocket depths, attachment levels were assessed at baseline, 1 month, and
      1 year after implementation of the treatment protocol. RESULTS: Treatment success
      was achieved in eight of the nine patients (and in 11 of the 13 implants)
      according to the success criteria adopted by the authors of this study.
      DISCUSSION: Infection control lies at the heart of peri-implant treatment. The
      control of three factors such as optimal diagnosis, removal of the aetiological
      factor of the disease (proper removal of debris and decontamination of the peri
      implant sulcus/pocket) and a good patient's oral hygiene self-care represents the
      key to success, resulting in good treatment outcomes when managing peri-implant
      pathologies. The protocol used (irrigation of peri-implant pockets with
      chlorhexidine gel delivered by a plastic needle) is considered to be of utility.

PMID- 16637911
TI  - Learning priorities and attitudes towards computer-assisted learning of general
      medical practitioners, general dental practitioners and dental hygienists.
AB  - OBJECTIVES: The objectives of this survey were to assess the attitudes and
      learning priorities of general medical practitioners (GMPs), general dental
      practitioners (GDPs), and dental hygienists (DHs) working at Jordan University of
      Science and Technology (JUST), Irbid, Jordan in relation to post-graduate
      education, to gather information on their attitudes and skills in using computers
      and computer-assisted learning (CAL) and to see whether the material in this form
      is acceptable to participate as a means of teaching. METHODS: Data for this study
      was gathered via a questionnaire distributed to 63 health professionals including
      GMPs, general dental practitioners and DHs (mean age 24.79 +/- 2.69 years)
      working at JUST. RESULTS: Of the 63 participants, 80% of the participants have
      home computers, 38% have office computers at work and only 25% have both home and
      office computers. Approximately 53% of the participants had their first CAL
      experience at home. Seventy-three of the participants indicated that connection
      to Internet is necessary for their work. Seventy-one of the participants were
      interested in the possibility of using CAL to further improve and increase their
      medical knowledge. The most important topic for doctors was 'learning about new
      techniques which may supersede those in current use', for DHs it was 'improve
      knowledge or skill in radiology', and for dentists it was 'reinforcement of well
      established techniques commonly used in dental practice'. CONCLUSIONS: It is
      necessary for practicing health care professionals to update themselves by taking
      continuous education courses after graduation more conveniently via CAL methods.

PMID- 16637912
TI  - Development of a stain shade guide to aid the measurement of extrinsic dental
      stain.
AB  - BACKGROUND: Accurate and reproducible assessment of extrinsic staining is pivotal
      to determining efficacy of some tooth whitening oral hygiene products. The aim of
      this study was: (1) to produce a stain shade guide to aid the in vitro and in
      vivo stain assessment (2) to assess intra- and inter-examiner reproducibility of
      stain assessment using the stain shade guide. METHOD: Using chlorhexidine and
      tea, perspex and acrylic teeth specimens were stained. The amount of staining on
      the perspex was measured with a spectrophotometer and the values obtained were
      assigned to the stained acrylic teeth, which were made into a stain guide. Using
      clinical photographs and a group of 10 volunteers, stain area and intensity were
      assessed using the stain guide and the recognized Lobene stain index by two
      examiners. The degree of intra- and inter-examiner reproducibility for these
      measurements were assessed using Cohen's kappa statistics. RESULTS: For both the
      clinical examination and use of photographs, intra-examiner reproducibility for
      stain intensity was improved when using the stain guide compared with the Lobene
      Index. Similarly, when assessing inter-examiner reproducibility, stain intensity
      kappa values were greater using the stain guide (kappa = 0.82) compared with the
      Lobene Index (kappa = 0.57). CONCLUSION: The findings of this study would suggest
      that the use of the stain guide could be of importance in the assessment of
      extrinsic dental stain.

PMID- 16637913
TI  - The effect of toothbrushing on secretion rate, pH and buffering capacity of
      saliva.

PMID- 16637914
TI  - Current advances in research that affect patient care.

PMID- 16637918
TI  - Immunology of disorders of neuromuscular transmission.
AB  - The neuromuscular junction (NMJ) is a prototype synapse and myasthenia gravis is
      the prototypic antibody-mediated disorder. There are now three other disorders of
      neuromuscular transmission caused by antibodies to other essential components of
      the NMJ. Antibodies to the muscle-specific kinase, MuSK, are defining a new form
      of myasthenia that can be associated with muscle atrophy. Antibodies to voltage
      gated calcium channels are responsible for muscle weakness and autonomic
      dysfunction in the Lambert Eaton myasthenic syndrome. Antibodies to voltage-gated
      potassium channels are found in patients with a range of disorders affecting the
      NMJ, the autonomic system or the central nervous system. The pathogenic
      mechanisms probably depend on the IgG subclass of the antibodies and are only
      partly shared between the diseases.

PMID- 16637919
TI  - Clinical aspects of neuromuscular transmission disorders.
AB  - Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs)
      directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG)
      is due, in most cases, to abs against the nicotinic acetylcholine receptor
      (AChR). Anti-AChR-positive MG actually includes different disease entities:
      weakness can be confined to extrinsic ocular muscles or can be generalized;
      patients with generalized MG (G-MG) can be subdivided on the basis of age of
      onset, HLA association and thymic pathology. About 15% of G-MG patients are anti
      AChR-negative; in a proportion of these cases serum abs against the muscle-
      specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by
      predominant involvement of bulbar muscles and very low frequency of thymic
      pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against
      voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle
      weakness and autonomic disturbances and it is paraneoplastic in over 50% of the
      cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be
      due to anti-voltage-gated potassium channel abs, signs of peripheral nerve
      hyperexcitability can be associated with CNS features.

PMID- 16637920
TI  - Thymus and myasthenia gravis: antigen processing in the human thymus and the
      consequences for the generation of autoreactive T cells.
AB  - Peptides displayed by antigen presenting cells in the thymus shape the T cell
      repertoire. We investigated the antigen processing machinery of the MHC class II
      presentation pathway and describe the differential expression of lysosomal
      proteases in compartments of the thymus and the peripheral lymphoid tissue.
      Overexpression of certain proteases found in the thymus and thymoma associated
      with myasthenia gravis is likely to affect tolerance induction and may promote
      the generation autoreactive CD4(+) T helper cells.

PMID- 16637921
TI  - Basic and clinical aspects of autoimmune disorders in peripheral nerves.
AB  - This presentation discusses the immunobiology of the Guillain Barre syndromes
      (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. By
      gaining an understanding of the clinical and pathophysiological pathways
      operating in GBS, we can hope to develop novel immunotherapies that will improve
      clinical outcome. Here we focus on GBS mediated by anti-ganglioside antibodies
      and highlight the correlations between anti-ganglioside antibody patterns and
      clinical phenotypes, the development of models of GBS, and the application of
      novel therapies based on inhibition of complement activation.

PMID- 16637922
TI  - Titin and ryanodine receptor antibodies in myasthenia gravis.
AB  - Some myasthenia gravis (MG) patients have antibodies against skeletal muscle
      antigens in addition to the acetylcholine receptor (AChR). Two major antigens for
      non-AchR antibodies in MG are the Ca(2+) release channel of the sarcoplasmic
      reticulum, the ryanodine receptor (RyR) and titin, a gigantic filamentous muscle
      protein essential for muscle structure, function and development. RyR and titin
      antibodies are found mainly in thymoma MG patients and in a few late-onset MG
      patients and correlate with a severe MG disease. The presence of titin
      antibodies, which bind to key regions near the A/I junction and in the central I
      band, correlates with myopathy. The immunosuppressant (FK506), which enhances
      Ca(2+) release from the RyR, seems to have a symptomatic effect on MG patients
      with RyR antibodies. The RyR antibodies recognize a region near the N-terminus
      important for channel regulation and inhibit Ca(2+) release in vitro. However,
      evidence that antibodies against the intracellular antigens RyR and titin are
      pathogenic in vivo is still missing.

PMID- 16637923
TI  - Myasthenia gravis: disease severity and prognosis.
AB  - OBJECTIVES: To examine myasthenia gravis (MG) severity and long-term prognosis in
      seronegative, seropositive, and thymoma MG. MATERIALS AND METHODS: Four series of
      patients were studied retrospectively. Severity and treatment were assessed each
      year, and muscle antibodies were assayed. RESULTS: Seropositive MG patients had a
      more severe course than seronegative MG patients. MG severity was higher in non
      thymectomized compared to thymectomized early-onset MG patients. MG severity did
      not differ between thymectomized and non-thymectomized late-onset patients. There
      was no significant difference in MG severity between thymoma and non-thymoma MG
      patients. CONCLUSIONS: MG is more severe in seropositive MG patients. With proper
      treatment, especially early thymectomy, the long-term prognosis is good in
      seropositive MG patients. The present studies indicate a benefit of thymectomy in
      early-onset MG, but no dramatic benefit in late-onset MG. Similar MG severity and
      outcome was seen in thymoma and non-thymoma MG.

PMID- 16637924
TI  - Artrogryposis multiplex congenita -- a rare fetal condition caused by maternal
      myasthenia gravis.
AB  - OBJECTIVES: To look at the occurrence of arthrogryposis multiplex congenita in
      newborn of mothers with myasthenia gravis (MG) and factors connected to this.
      MATERIAL AND METHODS: We retrospectively studied 176 births by 79 MG mothers,
      recorded in the Medical Birth Registry of Norway (MBRN). Four (2.2%) newborns
      (including one pair of twins) born with severe skeletal anomalies were
      identified. RESULTS: All four children died. Three had findings consistent with
      arthrogryposis multiplexa congenita (AMC), one had a fetal akinesia deformation
      sequence (FADS). The mother of the child with FADS had previously given birth to
      a child with neonatal MG. She was now in complete MG remission. The mother of the
      twins with AMC later gave birth to a child with neonatal MG. CONCLUSION: Siblings
      of an affected child -- either with neonatal MG or AMC -- have an increased risk
      to develop either neonatal MG or AMC. As this appears to be independent of the MG
      mother's clinical state, it is important to discuss previous pregnancy outcomes
      with all female MG patients.

PMID- 16637925
TI  - Effects of myasthenia gravis patient sera on human myoblast cultures.
AB  - OBJECTIVES: To investigate the role of acetylcholine receptor (AChR) and other
      anti-muscle autoantibodies in myasthenia gravis (MG). Since many of these
      autoantibodies target proteins with structural or signalling functions, we
      examined the effect of MG sera on muscle cell morphology. MATERIALS AND METHODS:
      Primary human myoblast cultures were exposed to MG sera and morphological changes
      observed by light and fluorescence microscopy. RESULTS: MG patient sera caused
      changes in cell shape (cell retraction) and led to the formation of inclusion
      bodies and intracellular vesicles. A disordered arrangement of actin
      microfilaments was also observed. The effects were not complement-mediated, were
      both dose- and time-dependent, and appeared to correlate with disease severity of
      the MG donor. CONCLUSION: The factors responsible for these effects in vitro may
      also play a role in the pathogenesis of MG in vivo. Further study of these
      factors may improve our understanding of MG pathogenesis.

PMID- 16637926
TI  - Does myasthenia gravis provide protection against cancer?
AB  - OBJECTIVES: Reports have been made of an altered rate of extrathymic malignancies
      in patients with myasthenia gravis (MG). This study compared the rate of such
      malignancies in a group of MG patients with an optimal control group. MATERIALS
      AND METHODS: From the Norwegian Cause of Death Registry, we identified 249 dead
      MG patients (1951-2001) and a control group of 1,245 individuals (five per
      patient) dead in the same period, matched for sex and year of birth. RESULTS:
      Patients with MG had a lower occurrence of malignant disease as underlying or
      contributing cause of death than the controls (8.8% vs 27.2%, P < 0.001). The
      main difference was found for colorectal cancer, breast cancer and cancer in the
      upper digestive tract (esophagus and stomach). CONCLUSIONS: We report a
      significantly lower rate of extrathymic malignancies in patients with MG than in
      controls, and we hypothesize that MG treatment or the immunological mechanisms
      involved in MG may protect patients with MG from developing an extrathymic
      malignancy.

PMID- 16637927
TI  - The Norwegian Multiple Sclerosis National Competence Centre and National Multiple
      Sclerosis registry -- a resource for clinical practice and research.
AB  - The Norwegian Multiple Sclerosis National Competence Centre was established at
      the Department of Neurology, Haukeland University Hospital, Bergen in 1996.
      Promotion of research, supervision and education of doctors and other health care
      professionals in Norway are the main responsibilities of the Centre. The centre
      has established national networks for MS care and research and has provided
      supervision and education of doctors and other health care professionals in
      Norway. Guidelines for diagnosis and treatment of MS have been established. The
      National Multiple Sclerosis Registry was established in 1998 and includes by
      January 2006 50-60% of all MS patients in Norway. Through a national
      collaboration, the registry aims for inclusion of a biobank unit for collection
      of cerebrospinal fluid and serum, DNA, and tissue samples.

PMID- 16637928
TI  - The basis for treatment in multiple sclerosis.
AB  - Contemporary licensed treatments for multiple sclerosis fail to provide a
      solution for the disease because their effects are limited to a modest reduction
      in the frequency of new episodes. They do not reduce disability or materially
      influence the progressive phase of the disease. A contemporary strategy for
      management requires a more detailed analysis of the separate contributions to the
      clinical features and overall course made by inflammation, axonal injury,
      compensatory mechanisms, and remyelination. From this formulation emerges the
      need either for early and fully effective suppression of the inflammatory
      response, limiting the damage to all components of the axon-glial unit; or the
      development of strategies for axonal and myelin repair that solve the issues of
      controlled differentiation, delivery and timing of these cell and growth factor
      based interventions.

PMID- 16637929
TI  - Grey matter pathology in multiple sclerosis.
AB  - Although multiple sclerosis (MS) has been considered a white matter disease, MS
      lesions are known to occur in grey matter. Recent immunohistochemical studies
      have demonstrated extensive grey matter demyelination in chronic MS. The most
      common lesion type consists of purely cortical lesions extending inward from the
      surface of the brain, this lesion subgroup is grossly underestimated by standard
      histochemical myelin staining methods. Some MS patients have subpial
      demyelination in all cortical areas of the brain; this pattern has been termed
      ''general cortical subpial demyelination''. Extensive cortical demyelination is
      associated with the progressive phases of disease, as less cortical demyelination
      has been detected in relapsing-remitting MS. The pathology of grey matter lesions
      differs from that of white matter lesions; grey matter lesions are less
      inflammatory, with less macrophage and lymphocyte infiltration. In purely
      cortical lesions there is no significant increase in lymphocytes compared with
      non-demyelinated adjacent cortical areas in MS patients or cerebral cortex in
      control patients. Significant axonal transection and neuronal loss have been
      demonstrated in grey matter MS lesions. Current magnetic resonance imaging (MRI)
      methods are not sensitive for purely cortical MS lesions. The clinical
      significance of cortical MS lesions may not be characterised until more sensitive
      MRI methods are developed.

PMID- 16637930
TI  - Planned vaginal births in women with multiple sclerosis: delivery and birth
      outcome.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of maternal
      multiple sclerosis (MS) on delivery and birth outcome in births without planned
      caesarean section. METHODS: Data were collected from the compulsory Medical Birth
      Registry of Norway from 1988 to 2002. Intended vaginal births in this time period
      were 449 births given by MS mothers and 851,060 control births. RESULTS: The MS
      mothers had a higher rate of induction of labour, and there was a strong trend
      for slower progression of second stage of labour and increased use of forceps.
      The MS group had lower birth weight and length of the neonates. The frequency of
      birth defects and the neonatal mortality were not increased in the MS group.
      CONCLUSIONS: Maternal MS affects the birth process and the neonate prenatally,
      even when the births with planned caesarean section are excluded. MS-related
      neuronal dysfunction linked to the uterus, is postulated as the most likely
      mechanism.

PMID- 16637931
TI  - Benign multiple sclerosis.
AB  - A small fraction of patients with multiple sclerosis (MS) have a benign course of
      the disease. The definition of benign MS has been heavily weighted towards
      physical disability and in particular ambulation. However, patients who are fully
      ambulatory may still be heavily disabled by non-motor symptoms like fatigue,
      pain, depression and cognitive dysfunction. These non-motor symptoms should be
      considered when defining benign MS.

PMID- 16637932
TI  - Multiplexed phosphoprotein analysis in immune cells.
AB  - Analyzing signaling networks in immune cells is of particular interests in
      diseases where treatment choices are preferentially immunomodulatory. By
      combining phospho-specific antibodies with multicolor flow cytometry it is
      possible to perform quantitative multiparameter analysis of signaling pathways
      within complex cell populations. Multiplexed phosphoprotein analysis will
      potentially incorporate environmental factors such as toxins or pathogens and
      genetic variability of individual patients in a step towards personalized
      medicine.

PMID- 16637933
TI  - FcgammaR and multiple sclerosis: an overview.
AB  - Receptors for the Fc domain of IgG (FcgammaR) play a key role in the immune
      system by linking the cellular and humoral immune systems. Despite extensive
      documentation of CNS-specific antibodies in cerebrospinal fluid and plaques in
      multiple sclerosis (MS) patients, the role of FcgammaR in this disease remains
      largely unexplored. Studies indicate however, that polymorphisms in some FcgammaR
      genes and treatment that induces FcgammaR on immune-competent cells could
      influence disease progression and treatment response.

PMID- 16637934
TI  - Onconeural antibodies are essential to diagnose paraneoplastic neurological
      syndromes.
AB  - Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of
      cancer that are not caused by the tumor and its metastasis or by infection,
      ischemia or metabolic disruptions. In most patients, the neurological disorder
      develops before the cancer becomes clinically overt and the patient is referred
      to the neurologist who has the charge of identifying a neurological disorder as
      paraneoplastic. They are usually severely disabling. PNS are rare and are seen in
      less than 1% of patients with cancer. PNS depend on an autoimmune process
      triggered by cancer and directed to antigens common to both the cancer and the
      nervous system designated as onconeural antigens. Because of their high
      specificity (>90%), the best way to diagnose neurological disorders as
      paraneoplastic is to identify one of the well-characterized onconeural antibodies
      in the patient's serum. In addition, as these antibodies are associated with a
      restricted range of cancer, they permit orientating the search of the underlying
      tumor at a stage where it is frequently not clinically overt. This is a critical
      point, as today the best way to stabilize PNS is probably to treat the cancer as
      soon as possible. Unfortunately, about one-third of the patients do not have
      detectable antibodies and 5-10% have an atypical antibody that is not well
      characterized.

PMID- 16637935
TI  - Autopsy findings in the nervous system and ovarian tumour of two patients with
      paraneoplastic cerebellar degeneration.
AB  - OBJECTIVES: To review autopsy findings in paraneoplastic cerebellar degeneration.
      MATERIALS AND METHODS: We report the autopsy results of two individuals with
      paraneoplastic cerebellar degeneration and ovarian cancer. RESULTS: Both patients
      had extensive loss of cerebellar Purkinje cells and general activation of
      microglia in the central nervous system, as well as signs of immunactivation in
      the medulla. CONCLUSION: The immunoactivation in PCD is widespread and involving
      more than the cerebellum.

PMID- 16637936
TI  - An immunoprecipitation assay for the detection of onconeural antibodies.
AB  - INTRODUCTION: Onconeural antibodies are found in some patients with cancer, and
      are associated with paraneoplastic neurological syndromes. METHOD: A multi-well
      adapted fluid-phase immunoassay using radiolabelled recombinant onconeural
      proteins for the detection of onconeural antibodies is described. RESULT AND
      CONCLUSION: This immunoprecipitation technique is more sensitive in detecting
      onconeural antibodies than immunohistochemistry and immune blots.

PMID- 16637937
TI  - cDNA expression library screening for identification of novel onconeural
      antigens.
AB  - Paraneoplastic neurological disorders occur as a remote effect of cancer. Tumor
      cells expressing neuron-specific proteins elicit an autoimmune response,
      resulting in the production of various antibodies. The antibodies are usually
      associated with different syndromes, but the identity of many of the antigens is
      still unknown. Screening a cDNA expression library is a powerful technique that
      allows identification of previously uncharacterized antigens. By using patient
      sera containing antibodies, the antigens of interest can be isolated and further
      characterized.

PMID- 16637939
TI  - To use or not to use. What influences why women veterans choose VA health care.
AB  - BACKGROUND AND OBJECTIVE: Effects of advances in Department of Veterans Affairs
      (VA) women's health care on women veterans' health care decision making are
      unknown. Our objective was to determine why women veterans use or do not use VA
      health care. DESIGN AND PARTICIPANTS: Cross-sectional survey of 2,174 women
      veteran VA users and VA-eligible nonusers throughout southern California and
      southern Nevada. MEASUREMENTS: VA utilization, attitudes toward care, and socio
      demographics. RESULTS: Reasons cited for VA use included affordability (67.9%);
      women's health clinic (WHC) availability (58.8%); quality of care (54.8%); and
      convenience (47.9%). Reasons for choosing health care in non-VA settings included
      having insurance (71.0%); greater convenience of non-VA care (66.9%); lack of
      knowledge of VA eligibility and services (48.5%); and perceived better non-VA
      quality (34.5%). After adjustment for socio-demographics, health characteristics,
      and VA priority group, knowledge deficits about VA eligibility and services and
      perceived worse VA care quality predicted outside health care use. VA users were
      less likely than non-VA users to have after-hours access to nonemergency care,
      but more likely to receive both general and gender-related care from the same
      clinic or provider, to use a WHC for gender-related care, and to consider WHC
      availability very important. CONCLUSIONS: Lack of information about VA,
      perceptions of VA quality, and inconvenience of VA care, are deterrents to VA use
      for many women veterans. VA WHCs may foster VA use. Educational campaigns are
      needed to fill the knowledge gap regarding women veterans' VA eligibility and
      advances in VA quality of care, while VA managers consider solutions to after
      hours access barriers.

PMID- 16637940
TI  - Barriers to Veterans Health Administration care in a nationally representative
      sample of women veterans.
AB  - BACKGROUND: Women veterans are generally less healthy than their nonveteran
      female counterparts or male veterans. Accumulating evidence suggests there may be
      barriers to women veterans' access to and use of Veterans Health Administration
      (VHA) care. OBJECTIVE: To document perceived and/or actual barriers to care in a
      nationally representative sample of women veterans and examine associations with
      VHA use. DESIGN: Cross-sectional telephone survey. PARTICIPANTS: Women who are
      current and former users of VHA from VA's National Registry of Women Veterans.
      MEASUREMENTS: Assessments of perceptions of VHA care, background characteristics,
      and health service use. RESULTS: Perceptions of VHA care were most positive
      regarding facility/physical environment characteristics and physician skill and
      sensitivity and least positive regarding the availability of needed services and
      logistics of receiving VHA care (M=0.05 and M=-0.10; M=-0.23 and M=-0.25,
      respectively). The most salient barrier to the use of VHA care was problems
      related to ease of use. Moreover, each of the barriers constructs contributed
      unique variance in VHA health care use above and beyond background
      characteristics known to differentiate current users from former VHA users (Odds
      ratio [OR]=4.03 for availability of services; OR=2.63 for physician sensitivity
      and skill: OR=2.70 for logistics of care; OR=2.30 for facility/physical
      environment). Few differences in barriers to care and their association with VHA
      health care use emerged for women with and without service-connected
      disabilities. CONCLUSIONS: Findings highlight several domains in which VHA
      decisionmakers can intervene to enhance the care available to women veterans and
      point to a number of areas for further investigation.

PMID- 16637941
TI  - Patient satisfaction of female and male users of Veterans Health Administration
      services.
AB  - OBJECTIVE: To compare patient satisfaction of male and female users of Veterans
      Health Administration (VHA) services. DESIGN: Cross-sectional study based on
      secondary analysis of data from VHA's Survey of Healthcare Experiences of
      Patients (SHEP). PATIENTS: National random sample of 107,995 outpatients and
      112,817 inpatients in FY2004. MEASURES: Patient's ratings of overall quality (OQ)
      and unique dimensions of satisfaction. Sociodemographic and health-related
      patient attributes. ANALYSIS: Bivariate unadjusted analyses of the association
      between gender and other patient attributes and the outcomes of OQ and dimensions
      of satisfaction were conducted followed by multivariate analyses for each
      outcome, adjusting for demographic and health variables. RESULTS: Significant
      differences between female and male reporting of satisfaction were found in the
      unadjusted analyses with males showing greater levels of satisfaction than
      females (P<.05). These differences disappeared or became smaller for both
      outpatient and inpatient services, after adjusting for covariates. For 6 of the
      inpatient dimensions (Transitions, Physical Comfort, Involvement Family and
      Friends, Courtesy, Coordination, and Access) males had higher satisfaction than
      females after statistical adjustment. CONCLUSIONS: After adjustment for patient
      attributes, female VHA outpatients report similar OQ with VHA services as male
      patients. The fact that some inpatient dimensions of satisfaction continued to
      show effects favoring males even after adjustment suggests areas for continued
      focus in improving health care quality. Covariate adjustment is essential for
      evaluating satisfaction with health care services. Breaking down overall
      satisfaction into independent aspects of services is useful. The SHEP survey has
      provided a useful tool for evaluating and improving satisfaction among its VHA
      veteran users.

PMID- 16637943
TI  - Determinants of contraceptive availability at medical facilities in the
      Department of Veterans Affairs.
AB  - OBJECTIVE: To describe the variation in provision of hormonal and intrauterine
      contraception among Veterans Affairs (VA) facilities. DESIGN: Key informant,
      cross-sectional survey of 166 VA medical facilities. Data from public use data
      sets and VA administrative databases were linked to facility data to further
      characterize their contextual environments. PARTICIPANTS: All VA hospital-based
      and affiliated community-based outpatient clinics delivering services to at least
      400 unique women during fiscal year 2000. MEASUREMENTS: Onsite availability of
      hormonal contraceptive prescription and intrauterine device (IUD) placement.
      RESULTS: Ninety-seven percent of facilities offered onsite prescription and
      management of hormonal contraception whereas 63% offered placement of IUDs. After
      adjusting for facility caseload of reproductive-aged women, 3 organizational
      factors were independently associated with onsite IUD placement: (1) onsite
      gynecologist (adjusted odds ratio [OR], 20.35; 95% confidence interval [CI], 7.02
      to 58.74; P<.001); (2) hospital-based in contrast to community-based practice
      (adjusted OR, 5.49; 95% CI, 1.16 to 26.10; P=.03); and (3) availability of a
      clinician providing women's health training to other clinicians (adjusted OR,
      3.40; 95% CI 1.19 to 9.76; P=.02). CONCLUSIONS: VA's provision of hormonal and
      intrauterine contraception is in accordance with community standards, although
      onsite availability is not universal. Although contraception is a crucial
      component of a woman's health maintenance, her ability to obtain certain
      contraceptives from the facility where she obtains her primary care is largely
      influenced by the availability of a gynecologist. Further research is needed to
      determine how fragmentation of women's care into reproductive and nonreproductive
      services impacts access to contraception and the incidence of unintended
      pregnancy.

PMID- 16637944
TI  - Health status among 28,000 women veterans. The VA Women's Health Program
      Evaluation Project.
AB  - BACKGROUND: Male veterans receiving Veterans Health Administration (VA) care have
      worse health than men in the general population. Less is known about health
      status in women veteran VA patients, a rapidly growing population. OBJECTIVE: To
      characterize health status of women (vs men) veteran VA patients across age
      cohorts, and assess gender differences in the effect of social support upon
      health status. DESIGN AND PATIENTS: Data came from the national 1999 Large Health
      Survey of Veteran Enrollees (response rate 63%) and included 28,048 women and
      651,811 men who used VA in the prior 3 years. MEASUREMENTS: Dimensions of health
      status from validated Veterans Short Form-36 instrument; social support (married,
      living arrangement, have someone to take patient to the doctor). RESULTS: In each
      age stratum (18 to 44, 45 to 64, and > or =65 years), Physical Component Summary
      (PCS) and Mental Component Summary (MCS) scores were clinically comparable by
      gender, except that for those aged > or =65, mean MCS was better for women than
      men (49.3 vs 45.9, P<.001). Patient gender had a clinically insignificant effect
      upon PCS and MCS after adjusting for age, race/ethnicity, and education. Women
      had lower levels of social support than men; in patients aged <65, being married
      or living with someone benefited MCS more in men than in women. CONCLUSIONS:
      Women veteran VA patients have as heavy a burden of physical and mental illness
      as do men in VA, and are expected to require comparable intensity of health care
      services. Their ill health occurs in the context of poor social support, and
      varies by age.

PMID- 16637945
TI  - Are there gender differences in diabetes care among elderly Medicare enrolled
      veterans?
AB  - OBJECTIVE: To examine gender differences in diabetes care process measures and
      intermediate outcomes among veteran clinic users. DESIGN: A retrospective cohort
      study using Veterans Health Administration (VHA) and Medicare files of VHA clinic
      users with diabetes. Diabetes care process measures were tests for hemoglobin A1c
      (HbA1c), low-density lipoprotein (LDL-C) values, and eye exams. Intermediate
      outcomes were HbA1c and LDL-C values below recommended thresholds. Chi-square
      tests and logistic regressions were used to assess gender differences.
      PARTICIPANTS: Study population included 3,225 women and 231,922 men veterans with
      diabetes, enrolled in Medicare fee-for-service and alive at the end of fiscal
      year 2000. RESULTS: Overall, there were no significant gender differences in
      HbA1c or LDL-C testing. However, women had higher rates in these process measures
      than men among the non-African American minorities. Women were more likely to
      have completed eye exams (odds ratio [OR]=1.11; 99% confidence interval
      [CI]=1.10, 1.23) but were less likely to have LDL-C under 130 mg/dL (OR=0.77; 99%
      CI=0.69, 0.87). CONCLUSIONS: Among VHA patients with diabetes, clinically
      significant gender inequality was not apparent in most of diabetes care measures.
      However, there was evidence of better care among nonwhite and non-African
      American women than their male counterparts. Further research on interaction of
      race and gender on diabetes care is needed. This includes evaluation of
      integrated VHA women's health programs as well as cultural issues. Lower LDL-C
      control among women suggests areas of unmet needs for women and opportunities for
      future targeted quality improvement interventions at system and provider levels.

PMID- 16637946
TI  - Women and war. What physicians should know.
AB  - Most of today's 1.7 million women veterans obtain all or most of their medical
      care outside the VA health care system, where their veteran status is rarely
      recognized or acknowledged. Several aspects of women's military service have been
      associated with adverse psychologic and physical outcomes, and failure to assess
      women's veteran status, their deployment status, and military trauma history
      could delay identifying or treating such conditions. Yet few clinicians know of
      women's military history--or of military service's impact on women's subsequent
      health and well being. Because an individual's military service may be best
      understood within the historical context in which it occurred, we provide a
      focused historical overview of women's military contributions and their steady
      integration into the Armed Forces since the War for Independence. We then
      describe some of the medical and psychiatric conditions associated with military
      service.

PMID- 16637947
TI  - Brief report: Gender and total knee/hip arthroplasty utilization rate in the VA
      system.
AB  - OBJECTIVE: Osteoarthritis (OA) is a leading cause of disability and is more
      prevalent in women than men. Total joint arthroplasty is an effective treatment
      option for end-stage OA. We examined gender differences in utilization rates of
      total knee/hip arthroplasty in the Veterans Administration (VA) system. METHODS:
      The sample consisted of all VA patients for fiscal year (FY) 1999, 50 years of
      age or older, with or without the diagnosis of OA in any joint. We calculated the
      odds of patients undergoing total knee/hip arthroplasty adjusting for age,
      comorbidities, and presence of OA. We included the hospital site as a random
      effects variable to adjust for clustering. RESULTS: Of the 1,968,093 (2.3% women)
      VA patients in FY 1999 who were 50 years of age or older, 329,461 (2.9% women)
      patients carried a diagnosis of OA. For women, 2-year adjusted odds of undergoing
      total knee or hip arthroplasty were 0.97 (0.83 to 1.14) and 1.00 (0.79 to 1.27),
      respectively. CONCLUSION: Among patients potentially at risk for the procedure,
      men and women in the VA system were equally likely to undergo knee/hip
      arthroplasty.

PMID- 16637948
TI  - Posttraumatic stress disorder screening status is associated with increased VA
      medical and surgical utilization in women.
AB  - BACKGROUND: Women with posttraumatic stress disorder (PTSD) report poor health,
      but associations with health care utilization are understudied. OBJECTIVE: To
      determine associations between medical/surgical utilization and PTSD in female
      Veterans Affairs (VA) patients. DESIGN: Prospective comparison of utilization
      rates between women screening positive or negative for PTSD on a mailed survey.
      SUBJECTS: Women receiving care at an urban VA medical center between October 1996
      and January 2000. MEASUREMENTS: Survey responses, including a validated screen
      for PTSD (PCL-C), and VA utilization data through September 2002. RESULTS: Two
      thousand five hundred and seventy-eight (2,578) women (78% of those eligible)
      completed the PCL-C; 858 (33%) of them screened positive for PTSD (PTSD+). In
      unadjusted models, PTSD+ women had higher rates of medical/surgical
      hospitalizations and surgical inpatient procedures. Among women ages 35 to 49,
      mean days hospitalized/100 patients/year was 43.4 (95% CI 26 to 61) for PTSD+
      women versus 17.0 (16 to 18) for PTSD negative (PTSD-) women. More PTSD+ women
      underwent surgical procedures (P<.001). Mean annual outpatient visits were
      significantly higher among PTSD+ women, including: emergency department (ED) (1.1
      [1.0 to 1.2] vs 0.6 [0.5 to 0.6]), primary care (3.2 [3.0 to 3.4] vs 2.2 [2.1 to
      2.3]), medical/surgical subspecialists (2.1 [1.9 to 2.3] vs 1.5 [1.4 to 1.6]),
      ancillary services (4.1 [3.7 to 4.5] vs 2.4 [2.2 to 2.6]), and diagnostic tests
      (5.6 [5.1 to 6.1] vs 3.7 [3.4 to 4.0]). In multivariate models adjusted for
      demographics, smoking, service access, and medical comorbidities, PTSD+ women had
      greater likelihood of medical/surgical hospitalization (OR=1.37 [1.04 to 1.79])
      and of being among the top quartile of patients for visits to the ED, primary
      care, ancillary services, and diagnostic testing. CONCLUSIONS: Female veterans
      who screen PTSD+ receive more VA medical/surgical services. Appropriateness of
      that care deserves further study.

PMID- 16637949
TI  - DSM-IV diagnosed posttraumatic stress disorder in women veterans with and without
      military sexual trauma.
AB  - BACKGROUND: This study compares rates of posttraumatic stress disorder (PTSD) in
      female veterans who had military sexual trauma (MST) with rates of PTSD in women
      veterans with all other types of trauma. METHODS: Subjects were recruited at the
      Women's Comprehensive Healthcare Center when attending medical or psychiatric
      appointments or through a mailing; 230 women agreed and 196 completed the study.
      They completed questionnaires on health and military history, along with the
      Stressful Life Events Questionnaire (SLEQ). Those who met DSM-IV PTSD Criterion A
      completed the PTSD Symptom Scale-Interview (PSS-I) on which PTSD diagnoses were
      based. RESULTS: Ninety-two percent reported at least 1 trauma. Forty-one percent
      had MST, alone or with other trauma, and 90% had other trauma, with or without
      MST. Overall, 43% of subjects with trauma had PTSD. Those with MST had higher
      rates of PTSD than those with other trauma. Sixty percent of those with MST had
      PTSD; 43% of subjects with other traumas (with or without MST) had PTSD. Military
      sexual trauma and other trauma both significantly predicted PTSD in regression
      analyses (P=.0001 and .02, respectively) but MST predicted it more strongly.
      Prior trauma did not contribute to the relationship between MST and PTSD.
      DISCUSSION: Findings suggest that MST is common and that it is a trauma
      especially associated with PTSD.

PMID- 16637950
TI  - Frequency of mastalgia among women veterans. Association with psychiatric
      conditions and unexplained pain syndromes.
AB  - OBJECTIVE: To determine the prevalence and frequency of mastalgia and its
      association with psychiatric conditions and unexplained pain syndromes. DESIGN,
      SETTING, AND PARTICIPANTS: Cross-sectional mailed survey completed by 1,219
      female veterans enrolled at the VA Puget Sound Health Care System in 1998.
      MEASUREMENTS: Breast pain in the past year, unrelated to pregnancy, was
      categorized as infrequent (< or =monthly) or frequent (> or =weekly) mastalgia.
      Surveys assessed posttraumatic stress disorder (PTSD), depression, panic
      disorder, and alcohol misuse with validated screening tests, as well as self
      reported past-year chronic pelvic pain, fibromyalgia, and irritable bowel
      syndrome. RESULTS: The response rate was 63%. Fifty-five percent of the
      respondents reported past-year mastalgia. Of these, 15% reported frequent
      mastalgia. Compared to women without mastalgia, women reporting frequent
      mastalgia were more likely to screen positive for PTSD (odds ratio [OR] 5.2, 95%
      confidence interval [CI] 3.2 to 8.4), major depression (OR 4.2, 2.6 to 6.9),
      panic disorder (OR 7.1, 3.9 to 12.8), eating disorder (OR 2.6, 1.5 to 4.7),
      alcohol misuse (OR 1.8, 1.1 to 2.8), or domestic violence (OR 3.1, 1.9 to 5.0),
      and to report fibromyalgia (OR 3.9, 2.1 to 7.4), chronic pelvic pain (OR 5.4, 2.7
      to 10.5), or irritable bowel syndrome (OR 2.8, 1.6 to 4.8). Women with infrequent
      mastalgia were also more likely than women without mastalgia to screen positive
      for PTSD, depression, or panic disorder, or report pelvic pain or irritable bowel
      syndrome, although associations were weaker than with frequent mastalgia.
      CONCLUSIONS: Like other unexplained pain syndromes, frequent mastalgia is
      strongly associated with PTSD and other psychiatric conditions. Clinicians seeing
      patients with frequent mastalgia should inquire about anxiety, depression,
      alcohol misuse, and trauma history.

PMID- 16637951
TI  - Television viewing practices and obesity among women veterans.
AB  - BACKGROUND: Obesity is epidemic in the U.S. and has been associated with
      television viewing. OBJECTIVE: To describe the association between obesity and
      television viewing practices among women veterans. DESIGN, SETTING AND
      PARTICIPANTS: Cross-sectional, mailed survey completed by 1,555 female veterans
      enrolled at the VA Puget Sound Health Care System in 2000. MEASUREMENTS AND
      METHODS: We used bivariate and multivariate analyses to assess the association of
      obesity (body mass index >30 kg/m2 based on self-reported height and weight) with
      self-reported number of hours of television or videos viewed per day, and
      frequency of eating meals or snacking while watching television, controlling for
      other covariates. RESULTS: Watching television >2 hours per typical day on week
      days and/or weekends was associated with obesity (P<.001), as was eating or
      snacking while watching television (P=.003). In multivariate logistic regression
      analyses, watching television >2 hours per day and eating or snacking while
      watching television were each associated with obesity (odds ratio [OR] 1.4, 95%
      confidence interval [CI] 1.1 to 1.8; and OR 1.3, 95% CI 1.0 to 1.7,
      respectively), after adjusting for demographic variables, smoking, physical
      activity, and depression. Results were similar when posttraumatic stress disorder
      was included in the model instead of depression. Women who both watched >2 hours
      of television per day and ate or snacked while viewing were almost twice as
      likely to be obese (OR 1.9, 95% CI 1.4 to 2.6). CONCLUSION: Watching television
      over 2 hours per day and eating while watching television were each associated
      with obesity among female VA patients and may be modifiable risk factors for
      obesity.

PMID- 16637952
TI  - The state of women veterans' health research. Results of a systematic literature
      review.
AB  - OBJECTIVE: Assess the state of women veterans' health research. DESIGN:
      Systematic review of studies that pertained specifically to or included explicit
      information about women veterans. A narrative synthesis of studies in 4
      domains/topics was conducted: Stress of military life; Health and performance of
      military/VA women; Health services research/quality of care; and Psychiatric
      conditions. MEASUREMENTS AND MAIN RESULTS: We identified 182 studies. Of these, 2
      were randomized-controlled trials (RCTs) and the remainder used observational
      designs. Forty-five percent of studies were VA funded. We identified 77 studies
      pertaining to the stress of military life, of which 21 reported on sexual
      harassment or assault. Rates of harassment ranged from 55% to 79% and rates of
      sexual assault from 4.2% to 7.3% in active duty military women and 11% to 48%
      among women veterans. Forty-two studies concerned the health and performance of
      military/VA women, with 21 studies evaluating sexual assault and posttraumatic
      stress disorder (PTSD) and their effect on health. Fifty-nine studies assessed
      various aspects of health services research. Eight studies assessed quality of
      care and 5, patient satisfaction. Twenty-five studies assessed utilization and
      health care organization, and findings include that women veterans use the VA
      less than men, that gender-specific reasons for seeking care were common among
      female military and veteran personnel, that provision of gender-specific care
      increased women veterans' use of VA, and that virtually all VAs have available on
      site basic women's health services. Fifty studies were classified as psychiatric;
      31 of these were about the risk, prevalence, and treatment of PTSD. CONCLUSIONS:
      Most research on VA women's health is descriptive in nature and has concerned
      PTSD, sexual harassment and assault, the utilization and organization of care,
      and various psychiatric conditions. Experimental studies and studies of the
      quality of care are rare.

PMID- 16637953
TI  - Toward a VA Women's Health Research Agenda: setting evidence-based priorities to
      improve the health and health care of women veterans.
AB  - The expansion of women in the military is reshaping the veteran population, with
      women now constituting the fastest growing segment of eligible VA health care
      users. In recognition of the changing demographics and special health care needs
      of women, the VA Office of Research & Development recently sponsored the first
      national VA Women's Health Research Agenda-setting conference to map research
      priorities to the needs of women veterans and position VA as a national leader in
      Women's Health Research. This paper summarizes the process and outcomes of this
      effort, outlining VA's research priorities for biomedical, clinical,
      rehabilitation, and health services research.

PMID- 16637954
TI  - The role of formative evaluation in implementation research and the QUERI
      experience.
AB  - This article describes the importance and role of 4 stages of formative
      evaluation in our growing understanding of how to implement research findings
      into practice in order to improve the quality of clinical care. It reviews
      limitations of traditional approaches to implementation research and presents a
      rationale for new thinking and use of new methods. Developmental, implementation
      focused, progress-focused, and interpretive evaluations are then defined and
      illustrated with examples from Veterans Health Administration Quality Enhancement
      Research Initiative projects. This article also provides methodologic details and
      highlights challenges encountered in actualizing formative evaluation within
      implementation research.

PMID- 16637955
TI  - Toward evidence-based quality improvement. Evidence (and its limitations) of the
      effectiveness of guideline dissemination and implementation strategies 1966-1998.
AB  - OBJECTIVES: To determine effectiveness and costs of different guideline
      dissemination and implementation strategies. DATA SOURCES: MEDLINE (1966 to
      1998), HEALTHSTAR (1975 to 1998), Cochrane Controlled Trial Register (4th edn
      1998), EMBASE (1980 to 1998), SIGLE (1980 to 1988), and the specialized register
      of the Cochrane Effective Practice and Organisation of Care group. REVIEW
      METHODS:  INCLUSION CRITERIA: Randomized-controlled trials, controlled clinical
      trials, controlled before and after studies, and interrupted time series
      evaluating guideline dissemination and implementation strategies targeting
      medically qualified health care professionals that reported objective measures of
      provider behavior and/or patient outcome. Two reviewers independently abstracted
      data on the methodologic quality of the studies, characteristics of study
      setting, participants, targeted behaviors, and interventions. We derived single
      estimates of dichotomous process variables (e.g., proportion of patients
      receiving appropriate treatment) for each study comparison and reported the
      median and range of effect sizes observed by study group and other quality
      criteria. RESULTS: We included 309 comparisons derived from 235 studies. The
      overall quality of the studies was poor. Seventy-three percent of comparisons
      evaluated multifaceted interventions. Overall, the majority of comparisons
      (86.6%) observed improvements in care; for example, the median absolute
      improvement in performance across interventions ranged from 14.1% in 14 cluster
      randomized comparisons of reminders, 8.1% in 4 cluster-randomized comparisons of
      dissemination of educational materials, 7.0% in 5 cluster-randomized comparisons
      of audit and feedback, and 6.0% in 13 cluster-randomized comparisons of
      multifaceted interventions involving educational outreach. We found no
      relationship between the number of components and the effects of multifaceted
      interventions. Only 29.4% of comparisons reported any economic data. CONCLUSIONS:
      Current guideline dissemination and implementation strategies can lead to
      improvements in care within the context of rigorous evaluative studies. However,
      there is an imperfect evidence base to support decisions about which guideline
      dissemination and implementation strategies are likely to be efficient under
      different circumstances. Decision makers need to use considerable judgment about
      how best to use the limited resources they have for quality improvement
      activities.

PMID- 16637956
TI  - Lessons learned about implementing research evidence into clinical practice.
      Experiences from VA QUERI.
AB  - The mission of the Veterans Health Administration's (VHA) quality enhancement
      research initiative (QUERI) is to enhance the quality of VHA health care by
      implementing clinical research findings into routine care. This paper presents
      lessons that QUERI investigators have learned through their initial attempts to
      pursue the QUERI mission. The lessons in this paper represent those that were
      common across multiple QUERI projects and were mutually agreed on as having
      substantial impact on the success of implementation. While the lessons are
      consistent with commonly recognized ingredients of successful implementation
      efforts, the examples highlight the fact that, even with a thorough knowledge of
      the literature and thoughtful planning, unexpected circumstances arise during
      implementation efforts that require flexibility and adaptability. The findings
      stress the importance of utilizing formative evaluation techniques to identify
      barriers to successful implementation and strategies to address these barriers.

PMID- 16637957
TI  - Understanding health care organization needs and context. Beyond performance
      gaps.
AB  - Significant efforts have been invested in improving our understanding of how to
      accelerate and magnify the impact of research on clinical practice. While
      approaches to fostering translation of research into practice are numerous, none
      appears to be superior and the evidence for their effectiveness is mixed. Lessons
      learned from formative evaluation have given us a greater appreciation of the
      contribution of context to successful implementation of quality improvement
      interventions. While formative evaluation is a powerful tool for addressing
      context effects during implementation, lessons learned from the social sciences
      (including management and operations research, sociology, and public health) show
      us that there are also powerful preimplementation tools available to us. This
      paper discusses how we might integrate these tools into implementation research.
      We provide a theoretical framework for our need to understand organizational
      contexts and how organizational characteristics can alert us to situations where
      preimplementation tools will prove most valuable.

PMID- 16637958
TI  - Using complexity theory to build interventions that improve health care delivery
      in primary care.
AB  - Previous observational research confirms abundant variation in primary care
      practice. While variation is sometimes viewed as problematic, its presence may
      also be highly informative in uncovering ways to enhance health care delivery
      when it represents unique adaptations to the values and needs of people within
      the practice and interactions with the local community and health care system. We
      describe a theoretical perspective for use in developing interventions to improve
      care that acknowledges the uniqueness of primary care practices and encourages
      flexibility in the form of intervention implementation, while maintaining
      fidelity to its essential functions.

PMID- 16637959
TI  - Using the six sigma process to implement the Centers for Disease Control and
      Prevention Guideline for Hand Hygiene in 4 intensive care units.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) Guideline for
      Hand Hygiene in Health Care Settings was issued in 2002. In 2003, the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO) established
      complying with the CDC Guideline as a National Patient Safety Goal for 2004. This
      goal has been maintained through 2006. The CDC's emphasis on the use of alcohol
      based hand rubs (ABHRs) rather than soap and water was an opportunity to improve
      compliance, but the Guideline contained over 40 specific recommendations to
      implement. OBJECTIVE: To use the Six Sigma process to examine hand hygiene
      practices and increase compliance with the CDC hand hygiene recommendations
      required by JCAHO. DESIGN: Six Sigma Project with pre-post design. PARTICIPANTS:
      Physicians, nurses, and other staff working in 4 intensive care units at 3
      hospitals. MEASUREMENTS: Observed compliance with 10 required hand hygiene
      practices, mass of ABHR used per month per 100 patient-days, and staff attitudes
      and perceptions regarding hand hygiene reported by questionnaire. RESULTS:
      Observed compliance increased from 47% to 80%, based on over 4,000 total
      observations. The mass of ABHR used per 100 patient-days in 3 intensive care
      units (ICUs) increased by 97%, 94%, and 70%; increases were sustained for 9
      months. Self-reported compliance using the questionnaire did not change. Staff
      reported increased use of ABHR and increased satisfaction with hand hygiene
      practices and products. CONCLUSIONS: The Six Sigma process was effective for
      organizing the knowledge, opinions, and actions of a group of professionals to
      implement the CDC's evidence-based hand hygiene practices in 4 ICUs. Several
      tools were developed for widespread use.

PMID- 16637960
TI  - Models, strategies, and tools. Theory in implementing evidence-based findings
      into health care practice.
AB  - This paper presents a case for careful consideration of theory in planning to
      implement evidence-based practices into clinical care. As described, theory
      should be tightly linked to strategic planning through careful choice or creation
      of an implementation framework. Strategies should be linked to specific
      interventions and/or intervention components to be implemented, and the choice of
      tools should match the interventions and overall strategy, linking back to the
      original theory and framework. The thesis advanced is that in most studies where
      there is an attempt to implement planned change in clinical processes, theory is
      used loosely. An example of linking theory to intervention design is presented
      from a Mental Health Quality Enhancement Research Initiative effort to increase
      appropriate use of antipsychotic medication among patients with schizophrenia in
      the Veterans Health Administration.

PMID- 16637961
TI  - Priorities and strategies for the implementation of integrated informatics and
      communications technology to improve evidence-based practice.
AB  - The U.S. health care system is one of the world's most advanced systems. Yet, the
      health care system suffers from unexplained practice variations, major gaps
      between evidence and practice, and suboptimal quality. Although information
      processing, communication, and management are key to health care delivery and
      considerable evidence links information/communication technology (IT) to
      improvements in patient safety and quality of care, the health care system has a
      longstanding gap in its investment. In the Crossing the Quality Chasm and
      Building a Better Delivery System reports, The Institute of Medicine and National
      Academy of Engineering identified IT integration as critical to improving health
      care delivery systems. This paper reviews the state of IT use in the U.S. health
      care system, its role in facilitating evidence-based practices, and identifies
      key attributes of an ideal IT infrastructure and issues surrounding IT
      implementation. We also examine structural, financial, policy-related, cultural,
      and organizational barriers to IT implementation for evidence-based practice and
      strategies to overcome them.

PMID- 16637962
TI  - Strategies for promoting organizational and practice change by advancing
      implementation research.
AB  - BACKGROUND: The persistence of a large quality gap between what we know about how
      to produce high quality clinical care and what the public receives has prompted
      interest in developing more effective methods to get evidence into practice.
      Implementation research aims to supply such methods. PURPOSE: This article
      proposes a set of recommendations aimed at establishing a common understanding of
      what implementation research is, and how to foster its development. METHODS: We
      developed the recommendations in the context of a translation research conference
      hosted by the VA for VA and non-VA health services researchers. IMPACTS: Health
      care organizations, journals, researchers and academic institutions can use these
      recommendations to advance the field of implementation science and thus increase
      the impact of clinical and health services research on the health and health care
      of the public.

PMID- 16637963
TI  - Moving implementation science forward.

PMID- 16637964
TI  - A state-of-the-art conference on implementing evidence in health care. Reasons
      and recommendations.

PMID- 16637965
TI  - Physician pay-for-performance. Implementation and research issues.
AB  - Recent research underscores the gaps that exist between evidence-based medical
      practices and the care that many patients actually receive. Recognizing this,
      large purchasers are experimenting with new reimbursement arrangements called pay
      for-performance (P4P) that tie a portion of payments for physician services to
      measures of quality. Agency theory, from the discipline of economics, provides a
      perspective on the challenges P4P is likely to encounter. The focus of most P4P
      initiatives on medical group performance raises additional questions about its
      potential effectiveness as a catalyst for change.

PMID- 16637966
TI  - Do contact lenses shape up?

PMID- 16637967
TI  - Orthokeratology review and update.
AB  - Orthokeratology (OK) is a clinical technique that uses specially designed rigid
      contact lenses to reshape the cornea to temporarily reduce or eliminate
      refractive error. This article reviews the history of traditional daily-wear OK
      (1960s to 1980s) and discusses the reasons for the recent resurgence in interest
      in the new modality of overnight OK, using reverse-geometry lens designs (1990s
      to the present). The clinical efficacy of the current procedure is examined and
      outcomes from clinical studies in terms of refractive error change and unaided
      visual acuity are summarised. Onset of the effects of overnight OK lens wear is
      rapid, with most change after the first night of lens wear and stability of
      refractive change after seven to 10 days. Mean reductions in myopic refractive
      error of between 1.75 and 3.33 D and individual reductions of up to 5.00 D have
      been reported. There appear to be slight reductions or minimal changes in
      astigmatism with the use of reverse-geometry lenses and most patients are
      reported to achieve 6/6 unaided vision or better. The induction of higher order
      aberrations, in particular, spherical aberration, has been reported and this may
      affect subjective vision under conditions of low contrast and pupil dilation.
      Patient satisfaction with overnight OK has been reported as similar to or better
      than with other popular modalities of contact lens wear. Available evidence
      suggests that the corneal changes induced by overnight OK are fully reversible.
      The refractive effect in OK is achieved by central epithelial thinning and this
      has raised concerns about compromise of the epithelial barrier to microbial
      infection. Recent reports of microbial keratitis in the modality are reviewed and
      the overall safety of the procedure is examined critically. Recent research on
      stromal contributions to the OK effect, particularly relating to overnight
      oedema, is summarised. Emerging issues in OK, including myopic control,
      correction of other refractive errors and permanency of the OK effect, are
      discussed.

PMID- 16637968
TI  - Search for coloured objects in natural surroundings by people with abnormal
      colour vision.
AB  - BACKGROUND: People with abnormal colour vision often report difficulty seeing
      coloured berries and flowers in foliage, which suggests they will have a
      diminished capacity for visual search when target objects are marked out by
      colour. There is very little experimental evidence of the effect of abnormal
      colour vision on visual search and none relating to search for objects in natural
      foliage. METHOD: We showed 79 subjects with abnormal colour vision (seven
      protanopes, 10 deuteranopes, 16 protanomals and 46 deuteranomals) and 20 subjects
      with normal colour vision photographs of natural scenes and asked them to locate
      clumps of red berries, to trace the length of a red string on grass and to name
      the season depicted in a photograph taken in the Autumn and the same scene
      photographed in the Summer. Colour vision was assessed using the Ishihara, the
      Medmont C100, the Farnsworth D15, the Richmond HRR and the Nagel anomaloscope.
      RESULTS: All the subjects with abnormal colour vision located fewer clumps of red
      berries than those with normal colour vision. The subjects who failed the
      Farnsworth D15 performed significantly worse than those who passed but the
      distribution of scores in the two groups overlaps. The majority of subjects with
      abnormal colour vision could not trace the full length of the string: only 38 per
      cent of anomalous trichromats who passed the Farnsworth D15 test and three per
      cent of those who failed it were able to trace the full length of the string.
      Fifty-five per cent of those classed as having a mild deficiency by the HRR test
      could trace the whole string. Most dichromats were unable to identify the Autumn
      season and those who did may have been assisted by guessing. Most (94 per cent)
      of those who passed the Farnsworth D15 test and all those classified as having a
      'mild' deficiency by the HRR test could identify the season. CONCLUSIONS: All
      people with abnormal colour vision, even those with a very mild deficiency, have
      some degree of impairment of their ability to see coloured objects in natural
      surroundings. A pass at the Farnsworth D15 test or a 'mild' classification with
      the Richmond HRR test identifies those likely to have the least problems with
      visual search and identification tasks. The results have practical implications
      for the selection of personnel in occupations that involve visual search in
      natural terrain.

PMID- 16637969
TI  - Visual and binocular status of Down syndrome children in Malaysia.
AB  - BACKGROUND: Down syndrome is a common chromosomal anomaly. Few reported studies
      make reference to the ocular status in Asian children with Down syndrome. The
      purpose of this study was to determine the visual and binocular status of a
      sample of Down syndrome children in Malaysia. METHODS: A total of 73 Malaysian
      children with Down syndrome (38 boys and 35 girls) in the Kuala Lumpur area aged
      one to 12 years were examined. Cycloplegic refraction was performed on each eye
      and binocular visual acuity was assessed using the Cardiff acuity card or the
      LogMAR chart. Binocular functions were assessed using the cover test and Lang's
      stereo acuity test. RESULTS: The mean age of the subjects was 6.01 +/- 3.41
      years. Refraction of the right eye showed that 10 per cent of the subjects were
      myopic, 20 per cent were hyperopic and 70 per cent had no significant refractive
      error. The mean spherical equivalent was +0.92 +/- 2.32 DS for the right eye and
      +0.99 +/- 2.21 DS for the left. The mean of binocular LogMAR VA was 0.36 +/- 0.22
      (6/12). Cover test revealed that 21 subjects had strabismus (of those, 33 per
      cent had unilateral esotropia, 52 per cent had alternating esotropia, nine per
      cent had unilateral exotropia and five per cent had alternating exotropia). Only
      22 subjects gave clear positive response to the stereotest. Other ocular findings
      included ptosis (one per cent), abnormal head posture (seven per cent) and
      nystagmus (six per cent). CONCLUSION: Malaysian children with Down syndrome have
      a high incidence of refractive error and strabismus. Regular visual examination
      is important so that corrective lenses can be prescribed to improve vision and to
      enhance the quality of life of these children in Malaysia.

PMID- 16637970
TI  - Statistical stereo-acuity norms in Saudi children.
AB  - PURPOSE: This paper aimed to study the norms for clinical stereo-acuity in Saudi
      children aged between six and 12 years and to determine the 95 per cent
      confidence limits for stereo-acuity thresholds in this group of subjects.
      METHODS: A total of 1,383 normal subjects (883 male and 500 female) aged between
      six and 12 years participated in this study. External examination, cover test,
      visual history and visual acuity were assessed for each subject prior to Titmus
      stereo-acuity measurement. RESULTS: The range of stereo-acuities attained by
      subjects for each age was 40 to 100 seconds of arc. The average stereo-acuity
      threshold showed an inverse (improved) relationship with the age of the subjects.
      CONCLUSION: This study indicates that not all children achieve the normal adult
      stereo-acuity of 40 seconds of arc by the age of 12 years. However, approximately
      99 per cent of all children up to and above the age of six years achieve stereo
      acuity thresholds of 80 seconds of arc or better. These results should serve as a
      guide when assessing the binocular vision status of school-aged children in Saudi
      Arabia.

PMID- 16637971
TI  - Repeatability and agreement of two A-scan ultrasonic biometers and IOLMaster in
      non-orthokeratology subjects and post-orthokeratology children.
AB  - PURPOSE: Our aim was to determine the repeatability of measurements of axial
      length (AL) and anterior chamber depth (ACD) made with two ultrasonic biometers
      and the IOLMaster in a group of non-orthokeratology (ortho-k) adult subjects and
      to investigate the agreement among instruments in children undergoing ortho-k
      therapy and in children wearing spectacles. METHODS: To determine repeatability,
      AL and ACD were measured twice in 22 non-ortho-k young adults using two A-scan
      ultrasonic biometers (A-5500 and A-2500) and the IOLMaster. To determine
      agreement, AL and ACD were measured with the same instruments in 30 children
      undergoing ortho-k therapy and 30 spectacle-wearing children. RESULTS: In the
      adult subjects, there were no significant differences in ACD and AL measurements
      obtained from the three instruments (repeated measures ANOVAs, p > 0.05). There
      was also no significant between-measurement difference for each instrument. The
      between-measurement agreement was better for the IOLMaster (95% limits of
      agreement (LA): -0.04 and +0.05 mm for both AL and ACD) than for the two A-scan
      ultrasonic biometers (95% LA: -0.12 and +0.11 mm for AL; -0.22 and +0.27 mm for
      ACD). Among the children, AL measurements with all three instruments were not
      significantly different from each other for both the children undergoing ortho-k
      therapy and those wearing spectacles (repeated measures ANOVAs, p > 0.05). The
      95% LA of differences obtained from any two instruments were also comparable for
      both groups of subjects (within -0.20 mm and +0.20 mm). ACD measurements of the
      children were significantly different among the three instruments (repeated
      measures ANOVAs, p < 0.05). No significant differences in ACD measurements were
      found between A-5500 and A-2500 for both groups of children (paired t tests, p >
      0.017). CONCLUSIONS: The repeatability of AL and ACD measurements with the
      IOLMaster was very good, and was better than with the A-scan ultrasonic
      biometers. The agreements in AL measurements between A-scan ultrasonic biometers
      and IOLMaster were comparable in both the ortho-k and the spectacle-wearing
      subjects, and were comparable to the repeatability of the A-scan ultrasonic
      biometers. ACD measurements between A-scan ultrasonic biometry and the IOLMaster
      were not comparable. AL measurements with the IOLMaster can replace the
      measurements from the two A-scan ultrasonic biometers used, however, the reverse
      is not true. AL and ACD measurements with all three instruments were unaffected
      by the flattened cornea following ortho-k lens wear.

PMID- 16637972
TI  - An unusual presentation of spontaneous sub-conjunctival haematoma in a patient
      receiving warfarin.
AB  - A 65-year-old man on warfarin therapy with a sudden spontaneous onset of sub
      conjunctival haematoma associated with bloody tears was assessed in the clinic
      following a referral from an optometrist. Due to discomfort, diplopia and
      lagophthalmos, the haematoma necessitated suspension of warfarin therapy and a
      surgical evacuation. The sub-conjunctival haematoma in a patient receiving
      warfarin can pose a significant management challenge.

PMID- 16637973
TI  - Basal cell carcinoma mistaken for actinic keratosis.
AB  - Increasing age and UV exposure are well-known associations with precancerous and
      cancerous skin lesions, including actinic (solar) keratosis, and squamous and
      basal cell carcinomata. This report describes a patient with a facial skin lesion
      close to an eye that was initially believed to be actinic (solar) keratosis but
      was subsequently diagnosed as a basal cell carcinoma (BCC). The diagnosis of BCC
      was helped pre-operatively by manipulation of the surrounding facial skin, which
      revealed the characteristic rolled edges and telangiectasis. Referral to his
      general medical practitioner (GP) resulted in surgical excision of the lesion.
      This procedure was performed inexpensively by the local GP as the lesion was not
      large and was in an accessible position. The lesion and the course of recovery
      over four weeks were documented photographically. The lesion was surgically
      excised and the diagnosis of basal cell carcinoma was confirmed by pathological
      examination. The wound healed well and the final cosmetic result was excellent.
      This patient illustrates the importance of careful observation and photo
      documentation of suspicious skin lesions. A review of the treatment options for
      these lesions is included in this report.

PMID- 16637974
TI  - How to make clinical decisions from statistics.
AB  - Best practice health care depends on clinicians understanding and applying the
      results of trials in clinical practice. These results are most often presented in
      the language of statistics, which can be bewildering and even misleading for
      those of us who have only a limited understanding of the terms used in reporting
      statistics. This communication provides a simple explanation of some of the more
      common types of trials and their descriptors, presented in a way that should
      allow clinicians to understand, assess and apply the results. Confidence
      intervals are increasingly used in clinical research reports. They can be gold
      mines of information because they not only provide an estimate of statistical
      significance but also define the limits of the measured parameters within which
      the true estimate lies, the clinical importance of the findings and the power of
      the study to make possible these estimates. The 'number needed' to treat is a
      readily understood descriptor and if not described in the report it can be
      calculated simply from the figures already published. These and other statistical
      descriptors are explained with simple formulae, from which they may be
      calculated.

PMID- 16637975
TI  - Colour-blindness detective story not so simple.

PMID- 16637979
TI  - Norman Brian Sims AM.

PMID- 16637985
TI  - Rain forest promotes trophic interactions and diversity of trap-nesting
      Hymenoptera in adjacent agroforestry.
AB  - 1. Human alteration of natural ecosystems to agroecosystems continues to
      accelerate in tropical countries. The resulting world-wide decline of rain forest
      causes a mosaic landscape, comprising simple and complex agroecosystems and
      patchily distributed rain forest fragments of different quality. Landscape
      context and agricultural management can be expected to affect both species
      diversity and ecosystem services by trophic interactions. 2. In Central Sulawesi,
      Indonesia, 24 agroforestry systems, differing in the distance to the nearest
      natural forest (0-1415 m), light intensity (37.5-899.6 W/m(-2)) and number of
      vascular plant species (7-40 species) were studied. Ten standardized trap nests
      for bees and wasps, made from reed and knotweed internodes, were exposed in each
      study site. Occupied nests were collected every month, over a period totalling 15
      months. 3. A total of 13,617 brood cells were reared to produce adults of 14 trap
      nesting species and 25 natural enemy species, which were mostly parasitoids. The
      total number of species was affected negatively by increasing distance from
      forest and increased with light intensity of agroforestry systems. The
      parasitoids in particular appeared to benefit from nearby forests. Over a 500-m
      distance, the number of parasitoid species decreased from eight to five, and
      parasitism rates from 12% to 4%. 4. The results show that diversity and
      parasitism, as a higher trophic interaction and ecosystem service, are enhanced
      by (i) improved connectivity of agroecosystems with natural habitats such as
      agroforestry adjacent to rain forest and (ii) management practices to increase
      light availability in agroforestry, which also enhances richness of flowering
      plants in the understorey.

PMID- 16637986
TI  - Breeding birds on small islands: island biogeography or optimal foraging?
AB  - 1. We test MacArthur and Wilson's theory about the biogeography of communities on
      isolated habitat patches using bird breeding records from 16 small islands off
      the coasts of Britain and Ireland. 2. A traditional examination of patterns of
      species richness on these islands suggests that area and habitat diversity are
      important predictors, but that isolation and latitude have a negligible impact in
      this system. 3. Unlike traditional studies, we directly examine the fundamental
      processes of colonization and local extinction (cessation of breeding), rather
      than higher-order phenomena such as species richness. 4. We find that many of
      MacArthur and Wilson's predictions hold: colonization probability is lower on
      more isolated islands, and extinction probability is lower on larger islands and
      those with a greater diversity of habitats. 5. We also find an unexpected
      pattern: extinction probability is much lower on more isolated islands. This is
      the strongest relationship in these data, and isolation is the best single
      predictor of colonization and extinction. 6. Our results show that examination of
      species richness alone is misleading. Isolation has a strong effect on both of
      the dynamic processes that underlie richness, and in this system, the reductions
      in both colonization and extinction probability seen on more distant islands have
      opposing influences on species richness, and largely cancel each other out. 7. We
      suggest that an appropriate model for this system might be optimal foraging
      theory, which predicts that organisms will stay longer in a resource patch if the
      distance to a neighbouring patch is large. If nest sites and food are the
      resources in this system, then optimal foraging theory predicts the pattern we
      observe. 8. We advance the hypothesis that there is a class of spatial systems,
      defined by their scale and by the taxon under consideration, at which decision
      making processes are a key driver of the spatiotemporal dynamics. The appropriate
      theory for such systems will be a hybrid of concepts from
      biogeography/metapopulation theory and behavioural ecology.

PMID- 16637987
TI  - Vole population cycles in northern and southern Europe: is there a need for
      different explanations for single pattern?
AB  - 1. Students of population cycles in small rodents in Fennoscandia have
      accumulated support for the predation hypothesis, which states that the gradient
      in cycle length and amplitude running from southern to northern Fennoscandia
      reflects the relative influence of specialist and generalist predators on vole
      dynamics, itself modulated by the presence of snow cover. The hypothesized role
      of snow cover is to isolate linked specialist predators, primarily the least
      weasel, Mustela n. nivalis L. and their prey, primarily field voles Microtus
      agrestis L., from the stabilizing influence of generalist predators. 2. The
      predation hypothesis does not readily account for the high amplitude and regular
      3-year cycles of common voles documented in agricultural areas of western,
      central and eastern Europe. Such cycles are rarely mentioned in the literature
      pertaining to Fennoscandian cycles. 3. We consider new data on population cycles
      and demographic patterns of common voles Microtus arvalis Pallas in south-west
      France. We show that the patterns are wholly consistent with five of six patterns
      that characterize rodent cycles in Fennoscandia and that are satisfactorily
      explained by the predation hypothesis. They include the: (a) existence of cycle;
      (b) the occurrence of long-term changes in relative abundance and type of
      dynamics; (c) geographical synchrony over large areas; (d) interspecific
      synchrony; and (e) voles are large in the increase and peak phase and small in
      decline and low phase, namely. There is a striking similarity between the
      patterns shown by common vole populations in south-west France and those from
      Fennoscandian cyclic rodent populations, although the former are not consistent
      with a geographical extension of the latitudinal gradient south of Fennoscandia.
      4. It is possible that the dominant interaction leading to multiannual rodent
      oscillations is different in different regions. We argue, however, that advocates
      of the predation hypothesis should embrace the challenge of developing a widely
      applicable explanation to population cycles, including justifying any limits to
      its applicability on ecological and not geographical grounds.

PMID- 16637988
TI  - Contrasting cascades: insectivorous birds increase pine but not parasitic
      mistletoe growth.
AB  - 1. Intraguild predation occurs when top predators feed upon both intermediate
      predators and herbivores. Intraguild predators may thus have little net impact on
      herbivore abundance. Variation among communities in the strength of trophic
      cascades (the indirect effects of predators on plants) may be due to differing
      frequencies of intraguild predation. Less is known about the influence of
      variation within communities in predator-predator interactions upon trophic
      cascade strength. 2. We compared the effects of a single predator community
      between two sympatric plants and two herbivore guilds. We excluded insectivorous
      birds with cages from ponderosa pine Pinus ponderosa trees parasitized by dwarf
      mistletoe Arceuthobium vaginatum. For 3 years we monitored caged and control
      trees for predatory arthropods that moved between the two plants, foliage-feeding
      caterpillars and sap-feeding hemipterans that were host-specific, and plant
      damage and growth. 3. Excluding birds increased the abundance of ant-tended
      aphids on pine and resulted in an 11% reduction in pine woody growth. Mutualist
      ants protected pine-feeding aphids from predatory arthropods, allowing aphid
      populations to burgeon in cages even though predatory arthropods also increased
      in cages. By protecting pine-feeding aphids from predatory arthropods but not
      birds, mutualist ants created a three-tiered linear food chain where bird effects
      cascaded to pine growth via aphids. 4. In contrast to the results for tended
      aphids on pine, bird exclusion had no net effects on untended pine herbivores,
      the proportion of pine foliage damaged by pine-feeding caterpillars, or the
      proportion of mistletoe plants damaged by mistletoe-feeding caterpillars. These
      results suggest that arthropod predators, which were more abundant in cages as
      compared with control trees, compensated for bird predation of untended pine and
      mistletoe herbivores. 5. These contrasting effects of bird exclusion support food
      web theory: where birds were connected to pine by a linear food chain, a trophic
      cascade occurred. Where birds fed as intraguild predators, the reticulate food
      webs linking birds to pine and mistletoe resulted in no net effects on herbivores
      or plant biomass. Our study shows that this variation in food web structure
      occurred between sympatric plants and within plants between differing herbivore
      guilds.

PMID- 16637989
TI  - Ontogeny of diving behaviour in the Australian sea lion: trials of adolescence in
      a late bloomer.
AB  - 1. Foraging behaviours of the Australian sea lion (Neophoca cinerea) reflect an
      animal working hard to exploit benthic habitats. Lactating females demonstrate
      almost continuous diving, maximize bottom time, exhibit elevated field metabolism
      and frequently exceed their calculated aerobic dive limit. Given that larger
      animals have disproportionately greater diving capabilities, we wanted to examine
      how pups and juveniles forage successfully. 2. Time/depth recorders were deployed
      on pups, juveniles and adult females at Seal Bay Conservation Park, Kangaroo
      Island, South Australia. Ten different mother/pup pairs were equipped at three
      stages of development (6, 15 and 23 months) to record the diving behaviours of 51
      (nine instruments failed) animals. 3. Dive depth and duration increased with age.
      However, development was slow. At 6 months, pups demonstrated minimal diving
      activity and the mean depth for 23-month-old juveniles was only 44 +/- 4 m, or
      62% of adult mean depth. 4. Although pups and juveniles did not reach adult
      depths or durations, dive records for young sea lions indicate benthic diving
      with mean bottom times (2.0 +/- 0.2 min) similar to those of females (2.1 +/- 0.2
      min). This was accomplished by spending higher proportions of each dive and total
      time at sea on or near the bottom than adults. Immature sea lions also spent a
      higher percentage of time at sea diving. 5. Juveniles may have to work harder
      because they are weaned before reaching full diving capability. For benthic
      foragers, reduced diving ability limits available foraging habitat. Furthermore,
      as juveniles appear to operate close to their physiological maximum, they would
      have a difficult time increasing foraging effort in response to reductions in
      prey. Although benthic prey are less influenced by seasonal fluctuations and
      oceanographic perturbations than epipelagic prey, demersal fishery trawls may
      impact juvenile survival by disrupting habitat and removing larger size classes
      of prey. These issues may be an important factor as to why the Australian sea
      lion population is currently at risk.

PMID- 16637990
TI  - Abiotic factors control invasion by Argentine ants at the community scale.
AB  - 1. A prominent and unresolved question in ecology concerns why communities differ
      in their susceptibility to invasion. While studies often emphasize biotic
      resistance, it is less widely appreciated how the physical environment affects
      community vulnerability to invasion. 2. In this study we performed field
      experiments to test how abiotic variation directly and indirectly influences the
      extent to which Linepithema humile Mayr (Argentine ants) invade seasonally dry
      environments in southern California. 3. In controlled and replicated experiments
      involving drip irrigation, we demonstrate (i) that elevated levels of soil
      moisture increased both the abundance of Argentine ants and their ability to
      invade native ant communities and (ii) that cessation of irrigation caused
      declines in the abundance of Argentine ants and led to their withdrawal from
      previously occupied areas. 4. Because drip irrigation stimulated plant growth, in
      an additional experiment we manipulated both soil moisture and plant cover to
      assess the direct vs. indirect effects of added water on the abundance of L.
      humile. 5. Local abundance of Argentine ants increased in irrigated plots but was
      38% higher in irrigated plots with plants compared to irrigated plots where plant
      growth was suppressed. The results of this experiment thus argue for a direct
      role of soil moisture in influencing Argentine ant abundance but suggest that
      that the indirect effects of added water may also be important. 6. Our study
      illustrates more generally that fine-scale variation in the physical environment
      can control whether communities become invaded by non-native species and suggests
      that an understanding of community susceptibility to invasion will be improved by
      a better appreciation of interactions between the biotic and abiotic environment.

PMID- 16637991
TI  - Sequentially assembled food webs and extremum principles in ecosystem ecology.
AB  - 1. Successional changes during sequential assembly of food webs were examined.
      This was carried out by numerical methods, drawing one species at a time from a
      species pool and obtaining the permanent (persistent) community emerging at each
      step. Interactions among species were based on some simple rules about body sizes
      of consumers and their prey, and community dynamics were described in terms of
      flows of biomass density. 2. Sequential assembly acted as a sieve on the
      communities, assembled communities having many properties different on average
      from those of feasible, stable communities taken at random from the species
      pools. 3. Time-series of community development were consistent with certain
      functions thought to go to an extremum (maximum or minimum) in ecosystem ecology,
      including a rapid early increase in net primary productivity and ascendency,
      although a clear trend in total biomass density was not evident and resilience
      decreased rather than increased. 4. In addition, more gradual changes in food web
      structure took place during succession to which the ecosystem goal functions were
      relatively insensitive. These changes included gradual increases in the number of
      species, invasion resistance, number of loops of length > 2 and number of prey
      species per consumer species. 5. We therefore argue that ecosystem and community
      dynamics can offer complementary insights into the process of ecological
      succession. The extremum principles of ecosystem ecology highlight some of the
      major properties of succession, whereas the community ecology sheds light on some
      more subtle changes taking place within the networks.

PMID- 16637992
TI  - The distribution of eggs per host in a herbivorous insect--intersection of
      oviposition, dispersal and population dynamics.
AB  - 1. The dynamics of parasitic organisms depend critically upon the frequency
      distribution of parasite individuals per host. However, the processes giving rise
      to this frequency distribution have rarely been modelled and tested for organisms
      with complex host selection behaviour. 2. In this study Microrhopala vittata, a
      chrysomelid beetle, was used to investigate how oviposition behaviour, movement
      and density of host plants interact in shaping the frequency distribution of egg
      clusters per host in the field. 3. Enclosures were stocked with two different
      host species and different beetle densities and various stochastic process models
      were fitted to egg cluster count data obtained from these enclosures. The
      different models were derived considering different scenarios, in particular
      whether or not plant density limits oviposition rate, whether or not ovipositing
      females actively seek out the most attractive plant within their perception
      radius and whether a female's oviposition rate is determined by plant intrinsic
      factors, the plant's egg cluster load or the surrounding beetle density. 4. The
      model parameters fitted to cage data were used to describe the frequency
      distribution of egg cluster counts obtained in a release experiment in the field.
      A total of 220 beetle pairs were released at five locations in a field where this
      beetle was not observed previously. Each release point was at a border between
      the two host species. 5. One model predicted for the preferred host species the
      egg cluster count frequencies in the field from parameters estimated in the
      cages. This model assumed that egg clusters present on a plant increased
      subsequent oviposition on this plant. All other models could not describe the
      distribution of egg cluster counts for either of the two host species. 6. The
      results suggest that females seek out attractive hosts actively and the
      attractiveness of a plant increases with its egg cluster load. This behaviour
      creates a frequency distribution of egg clusters per host that depends only on
      beetle density but not on plant density. This conclusion has important
      implications for modelling insect-plant interactions.

PMID- 16637993
TI  - Pheromone component patterns of moth evolution revealed by computer analysis of
      the Pherolist.
AB  - 1. The Pherolist internet site listing moth sex pheromone components reported in
      the literature was downloaded and processed by a basic program into a database
      with 2931 combinations of 377 unique chemical names of sex pheromone attractants
      used by 1572 moth species in 619 genera and 49 families. Names of pheromone
      compounds were analysed for aliphatic chain length, unsaturation position,
      geometric configuration, functional group (aldehyde, alcohol, acetate, epoxide,
      methyl-branched and hydrocarbon) and number of instances such combinations are
      used by species and families. 2. The analyses revealed pheromone blends of
      species ranged from one to eight components (45% species with one component, 36%
      two, 12% three, 5% four, 1% five, < or = 0.5% for > or = six). The numbers of
      different components of various chain lengths and functional groups, the numbers
      of instances such compounds are used by species and the numbers of species using
      such compounds are presented. 3. The average number of pheromone components per
      species increased as the number of species in a family increased based on linear
      regression of components in the 10 largest families, with species numbers ranging
      from 19 to 461. Pooling the four largest families gave a mean of 1.96 components
      per species that was significantly greater than the mean of the next 14 smaller
      families (1.63). Because related species in a large family would need more
      communication channels, this suggests that these species on average evolved to
      produce and detect more components in their pheromone blends to achieve a unique
      communication channel than was needed by species in smaller families. 4.
      Speciation in moths would entail evolutionary changes in both pheromone
      biosynthetic and sensory systems that avoided competition for communication
      channels of existing species. Regression analysis indicated that the more species
      in a family the more unique pheromone components, but the increase diminishes
      progressively. This suggests that, as the number of components increases with
      species number in a family, new species are more likely to evolve a unique blend
      comprising a communication channel from among existing components of the family.

PMID- 16637994
TI  - Stomach temperature telemetry reveals temporal patterns of foraging success in a
      free-ranging marine mammal.
AB  - 1. We studied feeding frequency in free-ranging grey seals using stomach
      temperature telemetry to test if previously reported sex differences in the
      diving, movement and diet were reflected in the temporal pattern of foraging
      success. 2. Data were retrieved from 21 of 32 grey seals from 1999 to 2001,
      totalling 343 days and 555 feeding events, with individual record length varying
      from 2 to 40 days (mean: 16.33 +/- 2.67 days/seal). 3. Seals fed on 57.8 +/-
      6.46% of days sampled and had an average of 1.7 +/- 0.26 meals per day, but
      individual variability was apparent in the temporal distribution of feeding as
      evidenced by high coefficients of variation (coefficient of variation = 69.0%).
      4. Bout analysis of non-feeding intervals of six grey seals suggests that feeding
      intervals of individuals were varied and probably reflect differences in prey
      availability. Grey seals tended to have many single feeding events with long
      periods separating each event, as would be expected for a large carnivore with a
      batch-reactor digestive system. 5. We found significant sex differences in the
      temporal distribution of feeding. The number of feeding events per day was
      greater in males (2.2 +/- 0.4 vs. 1.0 +/- 0.2), as was time associated with
      feeding per day (56.6 +/- 5.8 min vs. 43.9 +/- 9.4 min). 6. The number of feeding
      events varied with time of day with the least number occurring during dawn.
      Feeding event size differed significantly by time of day, with greater meal sizes
      during the dawn and the smallest meals during the night. 7. The length of time
      between meals increased with the size of the previous meal, and was significantly
      less in males (541.4 +/- 63.5 min) than in females (1092.6 +/- 169.9 min). 8.
      These results provide new insight into the basis of sex differences in diving and
      diet in this large size-dimorphic marine predator.

PMID- 16637995
TI  - The role of trout in stream food webs: integrating evidence from field surveys
      and experiments.
AB  - 1. We evaluated the effects of brown trout on boreal stream food webs using field
      surveys and enclosure/exclosure experiments. Experimental results were related to
      prey preference of uncaged trout in the same stream, as well as to a survey of
      macroinvertebrate densities in streams with vs. without trout. Finally, we
      assessed the generality of our findings by examining salmonid predation on three
      groups of macroinvertebrate prey (chironomid midges, epibenthic grazers,
      invertebrate predators) in a meta-analysis. 2. In a preliminary experiment,
      invertebrate predators showed a strong negative response to trout, whereas
      chironomids benefited from trout presence. In the main experiment, trout impact
      increased with prey size. Trout had the strongest effect on invertebrate
      predators and cased caddis larvae, whereas Baetis mayfly and chironomid larvae
      were unaffected. Trout impact on the largest prey seemed mainly consumptive,
      because prey emigration rates were low and independent of fish presence. Despite
      strong effects on macroinvertebrates, trout did not induce a trophic cascade on
      periphyton. Uncaged trout showed a strong preference for the largest prey items
      (predatory invertebrates and aerial prey), whereas Baetis mayflies and
      chironomids were avoided by trout. 3. Densities of invertebrate predators were
      significantly higher in troutless streams. Baetis mayflies also were less
      abundant in trout streams, whereas densities of chironomids were positively,
      although non-significantly, related to trout presence. Meta-analysis showed a
      strong negative impact of trout on invertebrate predators, a negative but
      variable impact on mobile grazers (mainly mayfly larvae) and a slightly positive
      impact on chironomid larvae. 4. Being size-selective predators, salmonid fishes
      have a strong impact on the largest prey types available, and this effect spans
      several domains of scale. Discrepancies between our experimental findings and
      those from the field survey and meta-analysis show, however, that for most lotic
      prey, small-scale experiments do not reflect fish impact reliably at stream-wide
      scales. 5. Our findings suggest that small-scale experiments will be useful only
      if the experimental results are evaluated carefully against natural history
      information about the experimental system and interacting species across a wide
      array of spatial scales.

PMID- 16637996
TI  - Recruitment pulses induce cannibalistic giants in Arctic char.
AB  - 1. Recent theoretical studies on the population dynamic consequences of
      cannibalism have focused on mechanisms behind the emergence of large cannibals
      (giants) in size-structured populations. Theoretically, giants emerge when a
      strong recruiting cohort imposes competition induced mortality on stunted adults,
      but also provides a profitable resource for a few adults that accelerate in
      growth and reach giant sizes. 2. Here the effects of a recruitment pulse on the
      individual and population level in an allopatric Arctic char population have been
      studied over a 5-year period and these results were contrasted with theoretical
      model predictions for the conditions necessary for the emergence of cannibalistic
      giants. 3. The recruitment pulse had negative effects on invertebrate resource
      abundance, and the decrease in body condition and increase in mortality of adult
      char suggested that strong intercohort competition took place. 4. The frequency
      of cannibalism increased and a few char accelerated in growth and reached 'giant'
      sizes. 5. The main discrepancy between model predictions and field data was the
      apparently small effect the recruited cohort had on resources and adult char
      performance during their first summer. Instead, the effects became pronounced
      when the cohort was 1 year old. This mismatch between model predictions and field
      observations was suggested to be due to the low per capita fecundity in char and
      the restricted nearshore habitat use in young-of-the-year (YOY) char. 6. This
      study provides empirical evidence that the emergence of giants is associated with
      the breakthrough of a strong recruiting cohort and also suggests that the claimed
      stable char populations with large cannibals may instead be populations with
      dynamic size structure that results in intermittent breakthroughs of recruitment
      pulses, providing the conditions necessary for char to enter the cannibalistic
      niche. 7. The data suggest that increased recruit survival through restricted
      habitat use may destabilize dynamics and cause the emergence of giants. However,
      they also suggest that this does not necessarily develop into populations with bi
      modal size structure in populations with low per capita fecundity and size- and
      density-dependent habitat use of recruiting cohorts.

PMID- 16637997
TI  - Spatio-temporal dynamics of alternative male phenotypes in coho salmon
      populations in response to ocean environment.
AB  - 1. The coexistence of alternative reproductive phenotypes will probably be shaped
      by spatial and temporal variability in the environment. However, the effects of
      such variability on coexistence and the scale at which it operates are seldom
      understood. 2. To quantify such effects, we examined spatial and temporal
      dynamics in the abundance and frequency of alternative phenotypes of male coho
      salmon, Oncorhynchus kisutch Walbaum, which mature as either large fighters (age
      3 'hooknoses') or small sneakers (age-2 'jacks'). Using over 20 years of data on
      coded-wire tagged fish released from nine Oregon hatcheries, we tested for the
      effects of ocean environment independent of those due to freshwater rearing. 3.
      Annual fluctuations of the abundance of jack and hooknose males within
      populations were correlated strongly by brood year (cohort) but not by return
      year (breeding group). This occurred independently of significant effects of
      release practice (i.e. the number of fish released, body size at release and date
      of release), indicating that a synchronized fluctuation in mortality during the
      first year at sea was the predominant cause. As a result, the annual frequency of
      the alternative phenotypes at breeding varied considerably within populations. 4.
      Spatial patterns in the annual fluctuations of the two phenotypes were similar
      (i.e. synchronous among populations), except that jacks showed local spatial
      structure (decreased synchrony with distance) not evident among hooknoses. This
      suggests that oceanic processes affecting the two phenotypes operate at different
      spatial scales. Despite effects on salmon abundance, the ocean environment had
      little influence through its effects on salmon growth on the relative frequencies
      of the alternative phenotypes within and among populations. 5. The results
      provide insight into the evolutionary dynamics of alternative phenotypes,
      including an intragenerational time lag that increases annual variability in
      phenotype frequencies at breeding (return years) and the significance of local
      freshwater processes, rather than oceanic processes, on phenotype expression.
      Freshwater processes, such as juvenile growth, timing of migration and breeding
      competition, operating at evolutionary and intragenerational time-scales, are
      probably the predominant forces affecting phenotype frequency.

PMID- 16637998
TI  - Quantitative analysis of bottlenose dolphin movement patterns and their
      relationship with foraging.
AB  - 1. Broad-scale telemetry studies have greatly improved our understanding of the
      ranging patterns and habitat-use of many large vertebrates. However, there often
      remains considerable uncertainty over the function of different areas or the
      factors influencing habitat selection. Further insights into these processes can
      be obtained through analyses of finer scale movement patterns. For example,
      search behaviour may be modified in response to prey distribution and abundance.
      2. In this study, quantitative analysis techniques are applied to the movements
      of bottlenose dolphins, recorded from land using a theodolite, to increase our
      understanding of their foraging strategies. Movements were modelled as a
      correlated random walk (CRW) and a biased random walk (BRW) to identify movement
      types and using a first-passage time (FPT) approach, which quantifies the time
      allocated to different areas and identifies the location and spatial scale of
      intensive search effort. 3. Only a quarter of the tracks were classed as CRW
      movement. Turning angle and directionality appeared to be key factors in
      determining the type of movement adopted. A high degree of overlap in search
      effort between separate movement paths indicated that there were small key sites
      (0.3 km radius) within the study area (4 km(2)). Foraging behaviour occurred
      mainly within these intensive search areas, indicating that they were feeding
      sites. 4. This approach provides a quantitative method of identifying important
      foraging areas and their spatial scale. Such techniques could be applied to
      movement paths for a variety of species derived from telemetry studies and
      increase our understanding of their foraging strategies.

PMID- 16637999
TI  - Delayed population explosion of an introduced butterfly.
AB  - 1. The causes of lagged population and geographical range expansions after
      species introductions are poorly understood, and there are relatively few
      detailed case studies. 2. We document the 29-year history of population dynamics
      and structure for a population of Euphydryas gillettii Barnes that was introduced
      to the Colorado Rocky Mountains, USA in 1977. 3. The population size remained low
      (< 200 individuals) and confined to a single habitat patch (approximately 2.25
      ha) to 1998. These values are similar to those of many other populations within
      the natural geographical range of the species. 4. However, by 2002 the population
      increased dramatically to > 3000 individuals and covered approximately 70 ha,
      nearly all to the south of the original site. The direction of population
      expansion was the same as that of predominant winds. 5. By 2004, the butterfly's
      local distribution had retracted mainly to three habitat patches. It thus
      exhibited a 'surge/contraction' form of population growth. Searches within 15 km
      of the original site yielded no other new populations. 6. In 2005, butterfly
      numbers crashed, but all three habitat patches remained occupied. The populations
      within each patch did not decrease in the same proportions, suggesting
      independent dynamics that are characteristic of metapopulations. 7. We postulate
      that this behaviour results, in this species, in establishment of satellite
      populations and, given appropriate habitat structure, may result in lagged or
      punctuated expansions of introduced populations.

PMID- 16638000
TI  - A truce with neutral theory: local deterministic factors, species traits and
      dispersal limitation together determine patterns of diversity in stream
      invertebrates.
AB  - 1. Studies seeking to explain local patterns of diversity have typically relied
      on niche explanations, reflected in correlations with local environmental
      conditions, or neutral theory, invoking dispersal processes and speciation. 2. We
      used macroinvertebrate community data from 10 streams that varied independently
      in local ecological conditions and spatial proximity. Neutral theory predicts
      that similarity in communities will be negatively associated with distance
      between sites, while niche theory suggests that community similarity will be
      positively associated with similarity in local ecological conditions. 3.
      Similarity in total invertebrate, grazer and predator assemblages showed negative
      relationships with distance and, for grazers and predators, positive
      relationships with local ecological conditions. However, the best model
      predicting community similarity in all three cases included aspects of both local
      ecological conditions and distance between sites. 4. When assemblages were
      analysed according to dispersal ability, high-dispersal species were shown to be
      freely accessing all sites and community similarity was not well predicted by
      either local ecology or spatial separation. Assemblages of species with low and
      moderate dispersal ability were best predicted by combined models, including
      distance between sites and local ecological factors. 5. The results suggest that
      the perceived dichotomy between neutral and local environmental processes in
      determining local patterns of diversity may not be useful. Neutral and niche
      processes structured these communities differentially depending on trophic level
      and species traits. 6. We emphasize the potential for both dispersal processes
      and local environmental conditions to explain local patterns of diversity.

PMID- 16638001
TI  - Testing five hypotheses of sexual segregation in an arctic ungulate.
AB  - 1. Sexual segregation occurs in most species of sexually dimorphic ungulates. At
      least five not mutually exclusive hypotheses have been formulated to explain
      patterns of social, habitat and spatial segregation; the indirect competition
      hypothesis (H1), the nutritional needs hypothesis (H2), the activity budget
      hypothesis (H3), the weather sensitivity hypothesis (H4), and the predation risk
      hypothesis (H5). 2. Each hypothesis has a unique set of predictions with respect
      to the occurrence of segregation, and how seasonality, density dependence and
      reproductive status affect sexual segregation. 3. We tested this set of
      predictions in order to separate the hypotheses H1-H5 for patterns of sexual
      segregation of the Svalbard reindeer based on 9 years data on seasonal estimates
      of spatial, habitat and social (i.e. grouping with their own sex) segregation in
      combination with resource selection functions. 4. Our results do not support that
      one single mechanism causes segregation. The activity budget hypothesis, the
      nutritional needs hypothesis and the weather sensitivity hypothesis were all
      partially supported, while the predation risk hypothesis was discarded for
      Svalbard reindeer because predators have been absent for at least 5000 years.
      Several mechanisms are thus interacting to explain the full-year pattern of
      sexual segregation and the combination of mechanisms varies among species and
      populations.

PMID- 16638002
TI  - Biodiversity as both a cause and consequence of resource availability: a study of
      reciprocal causality in a predator-prey system.
AB  - 1. One of the oldest questions in ecology is how species diversity in any given
      trophic level is related to the availability of essential resources that limit
      biomass (e.g. water, nutrients, light or prey). Researchers have tried to
      understand this relationship by focusing either on how diversity is influenced by
      the availability of resources, or alternatively, how resource abundance is
      influenced by species diversity. These contrasting perspectives have led to a
      seeming paradox '... is species diversity the cause or the consequence of
      resources that limit community biomass?' 2. Here we present results of an
      experiment that show it is possible for species diversity and resource density to
      exhibit reciprocal causal relationships in the same ecological system. Using a
      guild of ladybeetle predators and their aphid prey, we manipulated the number of
      predator species in field enclosures to examine how predator diversity impacts
      prey population size. At the same time, we manipulated the abundance of aphid
      prey in discrete habitat patches within each enclosure to determine how smaller
      scale spatial variation in resource abundance affects the number of co-occurring
      predator species. 3. We found that the number of ladybeetle species added to
      enclosures had a significant impact on aphid population dynamics because
      interference competition among the predators reduced per capita rates of
      predation and, in turn, the overall efficiency of the predator guild. At the same
      time, spatial variation in aphid abundance among smaller habitat patches
      generated variation in the observed richness of ladybeetles because more species
      occurred in patches where predators aggregated in response to high aphid density.
      4. The results of our experiment demonstrate that it is possible for species
      diversity to simultaneously be a cause and a consequence of resource density in
      the same ecological system, and they shed light on how this might occur for
      groups of mobile consumers that exhibit rapid responses to spatial and temporal
      variation in their prey.

PMID- 16638003
TI  - Ecological mechanisms favouring behavioural diversification in the absence of
      morphological diversification: a theoretical examination using brook charr
      (Salvelinus fontinalis).
AB  - 1. Behavioural diversification is thought to be an important initial step in the
      origin of resource polymorphisms. We developed a model for young brook charr
      (Salvelinus fontinalis Mitchill) to examine four mechanisms that could generate a
      U-shaped relationship between growth rate (fitness) and the proportion of time
      spent moving that would favour alternative foraging tactics in the absence of
      obvious differences in body size and shape. 2. Recently emerged brook charr of
      similar size and shape inhabit still-water pools along the sides of streams. Some
      individuals tend to sit and wait for crustacean prey at the pool substrate near
      the bank, while others tend to search actively for insect prey at the pool
      surface away from the bank. 3. The ecological mechanisms modelled were (i) the
      relationship between the rate of prey capture and the proportion of time spent
      moving is curvilinear, such that net rate of energy gain is maximized at two
      different levels of activity; (ii) switching between foraging locations and,
      hence, tactics involves lost opportunity and travel costs; (iii) switching
      between prey types and, hence, tactics involves a learning cost; and (iv)
      foraging success is status-dependent with individuals switching between tactics
      having a lower status than those specializing at a tactic. 4. Singly, no
      mechanism predicted the U-shaped relationship between growth rate and the
      proportion of time spent moving. Together, a U-shaped relationship was obtained,
      indicating that the behavioural diversification and diversifying selection
      observed in the field may be a consequence of multiple, subtle mechanisms.

PMID- 16638004
TI  - Climatic niche partitioning following successive invasions by fruit flies in La
      Reunion.
AB  - 1. Biological invasions have profound effects on community structure. The
      community composition following invasions can be influenced by the habitat
      diversity and the species' responses to abiotic factors. 2. We evaluated the
      tolerance to climatic factors and analysed the field distribution of four
      polyphagous fruit flies (Diptera: Tephritidae) of La Reunion Island (three exotic
      species that successively invaded the island and the endemic species Ceratitis
      catoirii) in order to evaluate the opportunities of coexistence by niche
      differentiation. 3. Atmospheric humidity and immersion in water in the laboratory
      greatly influence the survival of fruit fly pupae. While C. catoirii and C. rosa
      are very sensitive to desiccation, C. capitata and especially Bactrocera zonata
      are relatively tolerant. B. zonata also tolerated immersion in water much longer
      than did C. rosa and C. catoirii, that in turn were more resistant than C.
      capitata. Overall, field distributions agree with the predictions based on this
      study of humidity combined with previous data on the effects of temperature. 4.
      Climatic niche partitioning promotes coexistence between some but not all pairs
      of invasive species. Thus, C. rosa can coexist with both C. capitata and B.
      zonata at the regional scale, while climatic niches are not different enough to
      promote coexistence of the latter two species. The endemic species has no private
      climatic niche either and this now very rare species could be in the process of
      extinction. 5. By promoting coexistence or not, climatic diversity in invaded
      areas can directly affect the community composition following invasions.

PMID- 16638005
TI  - Multiscale patterns of movement in fragmented landscapes and consequences on
      demography of the snail kite in Florida.
AB  - 1. Habitat loss and fragmentation are major factors affecting vertebrate
      populations. A major effect of these habitat alterations is that they reduce
      movement of organisms. Despite the accepted importance of movement in driving the
      dynamics of many natural populations, movement of vertebrates in fragmented
      landscapes have seldom been estimated with robust statistical methods. 2. We
      estimated movement probabilities of snail kites Rosthramus sociabilis within the
      remaining wetlands in Florida. Using both radio-telemetry and banding
      information, we used a multistate modelling approach to estimate transition
      probabilities at two temporal scales (month; year) and multiple spatial scales.
      We examined kite movement among wetlands altered by three different levels of
      fragmentation: among wetlands separated by small physical barriers (e.g. road);
      among wetlands separated by moderate amount of matrix (< 5 km); and among
      wetlands separated by extensive matrix areas (> 15 km). 3. Kites moved
      extensively among contiguous wetlands (movement probability 0.29 per month), but
      significantly less among isolated wetlands (movement probability 0.10 per month).
      4. Kites showed high levels of annual site fidelity to most isolated wetlands
      (probability ranged from 0.72 to 0.95 per year). 5. We tested the effects of
      patch size and interpatch distance on movement. Our modelling indicated an effect
      of both distance and patch size on juveniles' movement (but not adult) when
      examining movements among fragments. 6. Only a small proportion of kites escaped
      a regional drought by moving to refugia (wetlands less affected by drought). Many
      individuals died after the drought. During drought adult survival dropped by 16%
      while juvenile survival dropped by 86% (possibly because juveniles were less
      likely to reach refugia). 7. We hypothesize that fragmentation may decrease
      kite's resistance to drought by restricting exploratory behaviour.

PMID- 16638006
TI  - Behavioural flexibility in the mating system buffers population extinction:
      lessons from the lesser spotted woodpecker Picoides minor.
AB  - 1. In most stochastic models addressing the persistence of small populations,
      environmental noise is included by imposing a synchronized effect of the
      environment on all individuals. However, buffer mechanisms are likely to exist
      that may counteract this synchronization to some degree. 2. We have studied
      whether the flexibility in the mating system, which has been observed in some
      bird species, is a potential mechanism counteracting the synchronization of
      environmental fluctuations. Our study organism is the lesser spotted woodpecker
      Picoides minor (Linnaeus), a generally monogamous species. However, facultative
      polyandry, where one female mates with two males with separate nests, was
      observed in years with male-biased sex ratio. 3. We constructed an individual
      based model from data and observations of a population in Taunus, Germany. We
      tested the impact of three behavioural scenarios on population persistence: (1)
      strict monogamy; (2) polyandry without costs; and (3) polyandry assuming costs in
      terms of lower survival and reproductive success for secondary males. We assumed
      that polyandry occurs only in years with male-biased sex ratio and only for
      females with favourable breeding conditions. 4. Even low rates of polyandry had a
      strong positive effect on population persistence. The increase of persistence
      with carrying capacity was slower in the monogamous scenario, indicating strong
      environmental noise. In the polyandrous scenarios, the increase of persistence
      was stronger, indicating a buffer mechanism. In the polyandrous scenarios,
      populations had a higher mean population size, a lower variation in number of
      individuals, and recovered faster after a population breakdown. Presuming a
      realistic polyandry rate and costs for polyandry, there was still a strong effect
      of polyandry on persistence. 5. The results show that polyandry and in general
      flexibility in mating systems is a buffer mechanism that can significantly reduce
      the impact of environmental and demographic noise in small populations.
      Consequently, we suggest that even behaviour that seems to be exceptional should
      be considered explicitly when predicting the persistence of populations.

PMID- 16638007
TI  - Habitat type and density influence vocal signal design in satin bowerbirds.
AB  - 1. This study provided a thorough test of the acoustic adaptation hypothesis
      using a within-species comparison of call structure involving a wide range of
      habitat types, an objective measure of habitat density and direct measures of
      habitat-related attenuation. 2. The structure of the bower advertisement call of
      the satin bowerbird was measured in 16 populations from throughout the species'
      range and related to the habitat type and density at each site. Transmission of
      white noise, pure tones and different bowerbird dialects was measured in five of
      six habitat types inhabited by satin bowerbirds. 3. Bowerbird advertisement call
      structure converged in similar habitats but diverged among different habitats;
      this pattern was apparent at both continent-wide and local geographical scales.
      Bowerbirds' call structures differed with changes in habitat density, consistent
      with the acoustic adaptation hypothesis. Lower frequencies and less frequency
      modulation were utilized in denser habitats such as rainforest and higher
      frequencies and more frequency modulation were used in the more open eucalypt
      dominated habitats. 4. The white noise and pure tone transmission measurements
      indicated that different habitats varied in their sound transmission properties
      in a manner consistent with the observed variation in satin bowerbird
      vocalizations. 5. There was no effect of geographical proximity of recording
      locations, nor was there the predicted inverse relationship between frequency and
      body size. 6. These findings indicate that the transmission qualities of
      different habitats have had a major influence on variation in vocal phenotypes in
      this species. In addition, previously published molecular data for this species
      suggest that there is no effect of genetic relatedness on call similarity among
      satin bowerbird populations.

PMID- 16638008
TI  - Hybridization increases measures of innate and cell-mediated immunity in an
      endangered bird species.
AB  - 1. Given the increasing threat of 'emerging infectious diseases' (EIDs), and the
      vulnerability of small inbred populations to such novel challenges (at least
      partly through compromised immunity), a degree of interspecific hybridization may
      improve the viability of endangered species by enriching depauperate gene pools.
      2. To investigate this hypothesis, we quantified indicators of the strength of
      both innate and cell-mediated immunity in wild populations of hybridizing
      parakeets on the Chatham Islands, New Zealand. 3. We show that both measures of
      immune function are markedly higher in the cosmopolitan red-crowned parakeet
      Cyanoramphus novaezelandiae than in the island endemic Forbes' parakeet C.
      forbesi, as is to be expected when comparing relatively outbred vs. relatively
      inbred species. 4. In addition, we show that both measures of immune function are
      higher in Forbes'x red-crowned parakeet hybrids than in the Forbes' parakeet.
      Even those individuals with few red-crowned characteristics, suggesting they are
      the products of matings between hybrids and Forbes' parakeets, have significantly
      higher measures of immune function. 5. As at least one of the immune indicators
      measured correlates directly with both survivorship and the viability of small
      bird populations, this study reveals a potential management option for
      hybridizing species of conservation concern, where an increase in resilience to
      novel disease challenges could outweigh some loss of genetic integrity.

PMID- 16638009
TI  - Nutrient transfer from sea to land: the case of gulls and cormorants in the Gulf
      of Maine.
AB  - 1. The structure of communities is influenced by the transport of resources
      across ecosystem boundaries. Seabirds are capable of introducing large amounts of
      marine-derived nutrients to land, thereby modifying resource availability to
      terrestrial species. 2. In this study we investigated the hypothesis that
      variation in nesting densities of great black-backed gulls Larus marinus and
      double-crested cormorants Phalacrocorax auritus would modify the effect of these
      species on soil nutrients and plant species composition on offshore islands in
      the Gulf of Maine, USA. 3. Our results showed a significant positive correlation
      between nest density and concentrations of ammonia and nitrate in soils, but no
      significant relationship between nest density and phosphate. Ammonia and
      phosphate concentrations were good predictors of plant species composition; there
      were more annual forbs than perennial grasses in the abandoned cormorant colony
      compared with the gull colonies. Extremely high concentrations of ammonia in the
      highest density colony (active cormorant) may have been the main factor
      inhibiting plant germination at this site. All of the plant species in gull and
      cormorant colonies showed enriched delta(15)N signatures, indicating substantial
      input of marine-derived nitrogen from seabirds. 4. Our study demonstrated that
      gulls and cormorants are effective vectors for the transport of marine nutrients
      to terrestrial ecosystems. However, transported nutrients occurred in
      particularly high concentrations in areas with nesting cormorants. Nesting
      densities and species-specific variation in resource transport should be
      considered when predicting the effects of seabirds and other biogenic vectors of
      allochthonous resources.

PMID- 16638010
TI  - Relationship between host abundance and parasite distribution: inferring
      regulating mechanisms from census data.
AB  - 1. We studied the effect of host abundance on parasite abundance and prevalence
      using data on 57 associations of fleas (Siphonaptera) and their mammalian hosts
      from Slovakia. 2. We assumed that flea-induced host mortality could be inferred
      from the relationship between flea aggregation and flea abundance, whereas host
      induced flea mortality could be inferred from the relationship between flea
      abundance or aggregation and host abundance. 3. Relationships between flea
      abundance or prevalence and host abundance were either negative (in 23 flea-host
      associations) or absent (in 34 flea-host associations). Negative relationships
      between flea abundance and host abundance were always accompanied by negative
      relationships between flea prevalence and host abundance. 4. The link between
      flea abundance/prevalence and host abundance was evaluated as the coefficient of
      determination of the respective regressions. Across flea-host associations, this
      link decreased with an increase in the degree of flea aggregation (measured as a
      parameter b of Taylor's power law). 5. Mean crowding of fleas decreased with an
      increase of host abundance in eight flea-host associations, being asymptotic in
      four of them. On the other hand, mean crowding of fleas increased with an
      increase in flea abundance in 49 flea-host associations, being asymptotic in 15
      of them. 6. Results of this study suggest that different flea-host associations
      are governed by different regulating mechanisms, but different regulation
      mechanisms may act simultaneously within the same flea-host associations.

PMID- 16638011
TI  - Self-regulation within outbreak populations of feral house mice: a test of
      alternative models.
AB  - 1. Outbreaks of feral house mice, Mus domesticus, in Australia represent a
      fundamental failure of the behavioural control mechanisms of population density,
      as proposed in the hypothesis of self-regulation. 2. Mice have the potential to
      keep numbers in check via a suite of spacing behaviours; however, the self
      regulation hypothesis implies that some social change occurs that permits the
      population to erupt. It also suggests that at different phases of an outbreak,
      distinct patterns of social activity are evident. 3. We compare predictions from
      two models encapsulating the self-regulation hypothesis as applied to feral house
      mice in south-eastern Australia. Each model may be distinguished by the timing of
      aggressiveness between mice that leads to a closed social system. We compare
      individual turnover, residency and territoriality in each sex and age cohort
      during the increase, peak and low phases of a population outbreak that peaked in
      2001. 4. The activity of 438 mice was monitored via intensive mark-recapture
      trapping and an automated event recording system that detected the activity of
      300 marked individuals at burrow entrances. 5. Our findings support the second
      model, which suggests that mice switch from an almost asocial structure at low
      densities to a territorial system as abundance increases. Adult females appear
      more likely than males or juveniles to make the significant social shift. The
      trigger for this change remains unclear and several alternative mechanisms are
      proposed.

PMID- 16638012
TI  - Silica in grasses as a defence against insect herbivores: contrasting effects on
      folivores and a phloem feeder.
AB  - 1. Silica, deposited as opaline phytoliths in the leaves of grasses, constitutes
      2-5% of dry leaf mass, yet its function remains unclear. It has been proposed
      that silica may act as an antiherbivore defence by increasing the abrasiveness
      and reducing the digestibility of grass leaves, although there is little direct
      experimental evidence to support this. 2. We investigated the effects of
      manipulated silica levels on the abrasiveness of the leaves of five grass
      species. We also examined the effects of silica levels on the feeding
      preferences, growth performance and digestion efficiency of two folivorous
      insects and one phloem-feeding insect. 3. Silica addition resulted in increases
      to leaf abrasiveness in four of the five grass species studied. Silica addition
      also deterred feeding by both folivores and reduced their growth rates and
      digestion efficiency. 4. These effects resulted in lower pupal mass of the
      lepidopteron larvae Spodoptera exempta and compensatory feeding by the
      orthopteran, Schistocerca gregaria. In contrast, silica had no effects on the
      feeding preference or the population growth of the phloem feeder, Sitobion
      avenae. 5. Our results demonstrate that silica is an effective defence against
      folivorous insects, both as a feeding deterrent, possibly mediated by increased
      abrasiveness, and as a digestibility reducer. The effects of silica on pupal mass
      and development time may impact on herbivore fitness and exposure to natural
      enemies. 6. These results are the first demonstration of a direct effect of
      silica on the abrasiveness of grasses and the adverse impact of silica on
      herbivore preference and performance.

PMID- 16638013
TI  - Density effects on life-history traits in a wild population of the great tit
      Parus major: analyses of long-term data with GIS techniques.
AB  - 1. Population density often has strong effects on the population dynamics and
      reproductive processes of territorial animals. However, most estimates of density
      dependent effects use the number of breeding pairs per unit area in a given
      season and look for correlations across seasons, a technique that assigns the
      same density score to each breeding pair, irrespective of local spatial
      variation. 2. In this study, we employed GIS techniques to estimate individual
      breeding densities for great tits breeding in Wytham Woods UK, between 1965 and
      1996. We then used linear mixed modelling to analyse the effect of density on
      reproductive processes. 3. The areas of Thiessen polygons formed around occupied
      nestboxes were used to approximate territory size (necessarily inverse of
      breeding density). There were significant, independent and positive relationships
      between clutch size, fledging mass and the number of offspring recruited to the
      population, and territory size (all P < 0.001), but no effect of territory size
      on lay-date or egg mass. 4. Thiessen polygons are contiguous and cover all of the
      available area. Therefore, at low nest densities territory polygons were
      excessively oversized. Using a novel procedure to address this limitation,
      territory sizes were systematically capped through a range of maxima, with the
      greatest effect in the models when territories were capped at 0.9-2.3 ha. This
      figure approximates to the maximum effective territory size in our population and
      is in close agreement with several field-based studies. This capping refinement
      also revealed a significant negative relationship between lay-date and territory
      size capped at 0.9 ha (P < 0.001). 5. These density-dependent effects were also
      detected when analyses were restricted to changes within individual females,
      suggesting that density effects do not merely result from either increased
      proportions of low-quality individuals, or increased occupation of poor sites,
      when population density is high. 6. Overall, these results suggest that, in the
      current population, great tits with territories smaller than c. 2 ha
      independently lay smaller and later clutches, have lighter fledglings, and
      recruit fewer offspring to the breeding population. These analyses thus suggest a
      pervasive and causal role of local population density in explaining individual
      reproductive processes.

PMID- 16638014
TI  - A silver spoon for a golden future: long-term effects of natal origin on fitness
      prospects of oystercatchers (Haematopus ostralegus).
AB  - 1. Long-term effects of conditions during early development on fitness are
      important for life history evolution and population ecology. Using multistrata
      mark-recapture models on 20 years of data, we quantified the relation between
      rearing conditions and lifetime fitness in a long-lived shorebird, the
      oystercatcher (Haematopus ostralegus). We addressed specifically the relative
      contribution of short- and long-term effects of rearing conditions to overall
      fitness consequences. 2. Rearing conditions were defined by differences in natal
      habitat quality, in which there is a clear dichotomy in our study population. In
      the first year of life, fledglings from high-quality natal origin had a 1.3 times
      higher juvenile survival. Later in life (age 3-11), individuals of high-quality
      natal origin had a 1.6 times higher adult prebreeder survival. The most striking
      effect of natal habitat quality was that birds that were reared on high-quality
      territories had a higher probability of settling in high-quality habitat (44% vs.
      6%). Lifetime reproductive success of individuals born in high-quality habitat
      was 2.2 times higher than that of individuals born in low-quality habitat. This
      difference increased further when fitness was calculated over several
      generations, due to a correlation between the quality of rearing conditions of
      parents and their offspring. 3. Long-term effects of early conditions contributed
      more to overall fitness differences as short-term consequences, contrary to
      common conceptions on this issue. 4. This study illustrates that investigating
      only short-term effects of early conditions can lead to the large underestimation
      of fitness consequences. We discuss how long-term consequences of early
      conditions may affect settlement decisions and source-sink population
      interactions.

PMID- 16638015
TI  - A neuroactive steroid 5alpha-androstane-3alpha,17beta-diol regulates androgen
      receptor level in astrocytes.
AB  - Optic nerve head (ONH) astrocytes from patients with glaucomatous optic
      neuropathy exhibit increased production of 5alpha-androstane-3alpha,17beta-diol
      (3alpha-diol), a neuroactive metabolite of 5alpha-dihydrotestosterone (5alpha
      DHT). To determine whether ONH astrocytes are androgen target cells, and whether
      3alpha-diol is capable of regulating astrocyte functions, we studied the response
      of human ONH astrocytes to 3alpha-diol compared with 17beta-hydroxy-17alpha
      methyl-estra-4,9,11-trien-3-one (R1881), a synthetic 5alpha-DHT agonist. In ONH
      astrocytes, both 3alpha-diol and R1881 increased protein levels of androgen
      receptor (AR) and glial fibrillary acidic protein (GFAP), however, only R1881
      also increased the AR mRNA level and astrocyte proliferation. Both R1881 and
      3alpha-diol rapidly activate the mitogen-activated protein kinase (MAPK)
      signaling pathway in ONH astrocytes, as confirmed by phosphorylation of
      extracellular signal-regulated kinase (ERK). 3Alpha-diol also activates the
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. 3Alpha-diol
      regulates the increase of AR protein level and the phosphorylation through the
      PI3K/Akt pathway, whereas R1881 regulates them through the MAPK/ERK pathway. Our
      findings demonstrate that human ONH astrocytes are androgen target cells and
      respond to androgens by the rapid activation of cell signaling. The activation of
      the PI3K/Akt pathway by 3alpha-diol may regulate various properties of
      astrocytes, including cell motility and survival, and may play a role in the
      formation and maintenance of the reactive phenotype of ONH astrocytes in
      glaucoma.

PMID- 16638016
TI  - Tumor necrosis factor-alpha activates signal transduction in hypothalamus and
      modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic
      neurotransmitters.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage
      syndrome that accompanies cancer and severe infectious diseases. More recently, a
      role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity
      has been shown. Much of the regulatory action exerted by TNF-alpha upon the
      control of energy stores depends on its action on the hypothalamus. In this
      study, we show that TNF-alpha activates canonical pro-inflammatory signal
      transduction pathways in the hypothalamus of rats. These signaling events lead to
      the transcriptional activation of an early responsive gene and to the induction
      of expression of cytokines and a cytokine responsive protein such as interleukin
      1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3,
      respectively. In addition, TNF-alpha induces the expression of neurotransmitters
      involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act
      directly in the hypothalamus inducing a pro-inflammatory response and the
      modulation of expression of neurotransmitters involved in energy homeostasis.

PMID- 16638017
TI  - Seeking long-term relationship: axon and target communicate to organize synaptic
      differentiation.
AB  - Synapses form after growing axons recognize their appropriate targets. The
      subsequent assembly of aligned pre and postsynaptic specializations is critical
      for synaptic function. This highly precise apposition of presynaptic elements
      (i.e. active zones) to postsynaptic specializations (i.e. neurotransmitter
      receptor clusters) strongly suggests that communication between the axon and
      target is required for synaptic differentiation. What trans-synaptic factors
      drive such differentiation at vertebrate synapses? First insights into the
      answers to this question came from studies at the neuromuscular junction (NMJ),
      where axon-derived agrin and muscle-derived laminin beta2 induce post and
      presynaptic differentiation, respectively. Recent work has suggested that axon-
      and target-derived factors similarly drive synaptic differentiation at central
      synapses. Specifically, WNT-7a, neuroligin, synaptic cell adhesion molecule
      (SynCAM) and fibroblast growth factor-22 (FGF-22) have all been identified as
      target-derived presynaptic organizers, whereas axon-derived neuronal activity
      regulated pentraxin (Narp), ephrinB and neurexin reciprocally co-ordinate
      postsynaptic differentiation. In addition to these axon- and target-derived
      inducers of synaptic differentiation, factors released from glial cells have also
      been implicated in regulating synapse assembly. Together, these recent findings
      have profoundly advanced our understanding of how precise appositions are
      established during vertebrate nervous system development.

PMID- 16638018
TI  - Neuropilin1 is a direct downstream target of Nurr1 in the developing brain stem.
AB  - The orphan nuclear receptor Nurr1 is expressed in the developing and adult
      central nervous system. Previous studies have shown that Nurr1 is essential for
      the generation of midbrain dopamine neurons. Furthermore, Nurr1 is critical for
      respiratory functions associated with the brain stem. Very few Nurr1 regulated
      genes have been identified and it remains unclear how Nurr1 influences the
      function and development of neurons. To identify novel Nurr1 target genes we have
      searched for regulated genes in the dopaminergic MN9D cell line. These
      experiments identified Neuropilin-1 (Nrp1), a receptor protein involved in axon
      guidance and angiogenesis, as a novel Nurr1 target gene. Nrp1 expression was
      rapidly up-regulated by Nurr1 in MN9D cells and in situ hybridization analysis
      showed that Nrp1 was coexpressed with Nurr1 in the brain stem dorsal motor
      nucleus. Importantly, Nrp1 expression was down-regulated in this area in Nurr1
      null mice. Moreover, two functional Nurr1 binding sites were identified in the
      Nrp1 promoter and Nurr1 was found to be recruited to these sites in MN9D cells,
      further supporting that Nrp1 is a direct downstream target of Nurr1. Taken
      together, our findings suggest that Nurr1 might influence the processes of axon
      guidance and/or angiogenesis via the regulation of Nrp1 expression.

PMID- 16638019
TI  - The role of LPA1 in formation of synapses among cultured hippocampal neurons.
AB  - We studied the lysophosphatidic acid receptor-1 (LPA1) gene, which we found to be
      expressed endogenously in cultured hippocampal neurons, and in vivo in young (1
      week-old) rat brain slices. Overexpressed green fluorescent protein (GFP)-tagged,
      membrane-associated LPA1 accumulated in a punctate manner over the entire
      dendritic tree and caused an increase in dendritic spine density. About half of
      the dendritic spines in the LPA1-transfected neurons displayed distinct
      fluorescent puncta, and this subset of spines was also substantially larger than
      puncta-free, LPA1-transfected or control GFP spines. This phenotype could also be
      seen in cells transfected with a ligand-binding, defective mutant and is
      therefore not dependent on interaction with an ambient ligand. While spontaneous
      miniature excitatory synaptic currents were of the same amplitudes, they decayed
      slower in LPA1-transfected neurons compared with GFP controls. We propose that
      LPA1 may play a role in the formation and modulation of the dendritic spine
      synapse.

PMID- 16638020
TI  - Quinolinic acid modulates the activity of src family kinases in rat striatum: in
      vivo and in vitro studies.
AB  - Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor
      (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable
      to free radicals, which can modulate protein tyrosine kinase (PTK) and
      phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases
      are associated with the NMDAR complex and regulate NMDA channel function. Because
      QA is an NMDAR agonist as well as a pro-oxidant agent, we investigated whether it
      may affect the activity of PTKs and PTPs in vivo and in vitro. In synaptosomes
      prepared from striata dissected 15 min, 30 min or 15 days after bilateral
      injection of QA we observed modulation of the phosphotyrosine pattern; a
      significant decrease in PTP activity; and a sustained increase in c-src and lyn
      activity at 15 and 30 min after treatment with QA, followed by a decrease 2 weeks
      later. Striatal synaptosomes treated in vitro with QA showed time- and dose
      dependent modulation of c-src and lyn kinase activities. Moreover, the nitric
      oxide synthase inhibitor NG-nitro-L-arginine-methyl ester, the NMDAR antagonist d
      2-amino-5-phosphonovaleric acid and pyruvate suppressed the QA-induced modulation
      of c-src activity. These findings suggest a novel feature of QA in regulating src
      kinase activity through the formation of reactive radical species and/or NMDAR
      overactivation.

PMID- 16638021
TI  - Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease
      expression early after spinal cord injury.
AB  - Minocycline, a clinically used tetracycline for over 40 years, crosses the blood
      brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse
      models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS)
      and is in clinical trial for sporadic ALS. Because apoptosis also occurs after
      brain and spinal cord (SCI) injury, its prevention may be useful in improving
      recovery. We analyzed minocycline's neuroprotective effects over 28 days
      following contusion SCI and found significant functional recovery compared to
      tetracycline. Histology, immunocytochemistry, and image analysis indicated
      statistically significant tissue sparing, reduced apoptosis and microgliosis, and
      less activated caspase-3 and substrate cleavage. Since our original report in
      abstract form, others have published both positive and negative effects of
      minocycline in various rodent models of SCI and with various routes of
      administration. We have since found decreased tumor necrosis factor-alpha, as
      well as caspase-3 mRNA expression, as possible mechanisms of action for
      minocycline's ameliorative action. These results support reports that modulating
      apoptosis, caspases, and microglia provide promising therapeutic targets for
      prevention and/or limiting the degree of functional loss after CNS trauma.
      Minocycline, and more potent chemically synthesized tetracyclines, may find a
      place in the therapeutic arsenal to promote recovery early after SCI in humans.

PMID- 16638023
TI  - Nitric oxide-producing microglia mediate thrombin-induced degeneration of
      dopaminergic neurons in rat midbrain slice culture.
AB  - Activated microglia are considered to play important roles in degenerative
      processes of midbrain dopaminergic neurons. Here we examined mechanisms of
      neurotoxicity of thrombin, a protease known to trigger microglial activation, in
      organotypic midbrain slice cultures. Thrombin induced a progressive decline in
      the number of dopaminergic neurons, an increase in nitric oxide (NO) production,
      and whole tissue injury indicated by lactate dehydrogenase release and propidium
      iodide uptake. Microglia expressed inducible NO synthase (iNOS) in response to
      thrombin, and inhibition of iNOS rescued dopaminergic neurons without affecting
      whole tissue injury. Inhibitors of mitogen-activated protein kinases (MAPKs) such
      as extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal
      kinase (JNK) attenuated thrombin-induced iNOS induction and dopaminergic cell
      death. Whole tissue injury was also attenuated by inhibition of ERK and p38 MAPK.
      Moreover, depletion of resident microglia from midbrain slices abrogated thrombin
      induced NO production and dopaminergic cell death, but did not inhibit tissue
      injury. Finally, antioxidative drugs prevented thrombin-induced dopaminergic cell
      death without affecting whole tissue injury. Hence, NO production resulting from
      MAPK-dependent microglial iNOS induction is a crucial event in thrombin-induced
      dopaminergic neurodegeneration, whereas damage of other midbrain cells is MAPK
      dependent but is NO-independent.

PMID- 16638025
TI  - Advice has changed for hormone therapy in the WHI era.

PMID- 16638022
TI  - Cyclopentenone isoprostanes are novel bioactive products of lipid oxidation which
      enhance neurodegeneration.
AB  - Oxidative stress and subsequent lipid peroxidation are involved in the
      pathogenesis of numerous neurodegenerative conditions, including stroke.
      Cyclopentenone isoprostanes (IsoPs) are novel electrophilic lipid peroxidation
      products formed under conditions of oxidative stress via the isoprostane pathway.
      These cyclopentenone IsoPs are isomeric to highly bioactive cyclopentenone
      prostaglandins, yet it has not been determined if these products are biologically
      active or are formed in the brain. Here we demonstrate that the major
      cyclopentenone IsoP isomer 15-A2t-IsoP potently induces apoptosis in neuronal
      cultures at submicromolar concentrations. We present a model in which 15-A2t-IsoP
      induced neuronal apoptosis involves initial depletion of glutathione and enhanced
      production of reactive oxygen species, followed by 12-lipoxygenase activation and
      phosphorylation of extracellular signal-regulated kinase 1/2 and the redox
      sensitive adaptor protein p66shc, which results in caspase-3 cleavage. 15-A2t
      IsoP application also dramatically potentiates oxidative glutamate toxicity at
      concentrations as low as 100 nm, demonstrating the functional importance of these
      molecules in neurodegeneration. Finally, we employ novel mass spectrometric
      methods to show that cyclopentenone IsoPs are formed abundantly in brain tissue
      under conditions of oxidative stress. Together these findings suggest that
      cyclopentenone IsoPs may contribute to neuronal death caused by oxidative
      insults, and that their activity should perhaps be addressed when designing
      neuroprotective therapies.

PMID- 16638026
TI  - Endogenous anti-oxidants in pregnancy and preeclampsia.
AB  - Oxidative stress has been implicated in a wide variety of diseases and
      degenerative states including cancer, rheumatoid arthritis, cardiovascular
      disease and ageing. There is now considerable evidence to suggest that pregnancy
      leads to the generation of an increased oxidative burden, but whether this
      overwhelms the anti-oxidant capacity within the placenta and/or the peripheral
      circulation remains a point of conjecture. There is little doubt that oxidative
      stress is a significant contributor in the pathogenesis of preeclampsia. The use
      of exogenous anti-oxidants such as vitamins C and E in the prevention of
      preeclampsia is the subject of several large clinical trials currently being
      conducted in many countries around the world. The results of these studies are
      eagerly awaited, but what of the endogenous anti-oxidant systems that have
      evolved to combat the oxidative burden associated with living in an aerobic
      environment? This review will focus on several important anti-oxidant enzyme
      systems, their role in pregnancy and the evidence to suggest that endogenous anti
      oxidants are important in the development of complications of pregnancy such as
      preeclampsia.

PMID- 16638027
TI  - Hormone therapy in the WHI era.
AB  - The announcement in July 2002 in the media of the results of the combined
      continuous hormone treatment arm of the Women's Health Initiative (WHI) had a
      profound effect on perceptions about hormone therapy among the lay public and the
      medical profession. Careful scrutiny of the announcement and the subsequent
      publications leads to the conclusion that the widespread fear of hormone therapy
      that was generated was not supported by the facts. WHI was not designed to be,
      nor can it be, interpreted as a randomised controlled trial of menopausal hormone
      therapy--rather, it was a trial of chronic disease prevention, particularly aimed
      at the possible cardiovascular benefits of a specific combination hormone therapy
      in postmenopausal women. The results, which were consistent with existing data,
      did not and do not warrant any major change in the previously established
      guidelines for the use of hormone therapy. Tibolone has emerged as an alternative
      treatment for menopausal symptoms, but its long-term benefits and risks have yet
      to be documented.

PMID- 16638028
TI  - Antenatal screening for Down syndrome in New Zealand: time for a national
      screening policy?

PMID- 16638029
TI  - Maternal serum activin A and the prediction of intrauterine growth restriction.
AB  - BACKGROUND: Differentiating between the small healthy fetus and the high risk
      growth restricted fetus remains a significant obstetric challenge. It has been
      previously shown that maternal activin A levels are increased in association with
      fetal growth restriction. AIM: To evaluate maternal serum activin A as a marker
      of fetal growth restriction. METHODS: Prospective cohort study of 62 women
      referred for fetal assessment because of a clinical suspicion of a small for
      gestation fetus. Maternal serum levels of activin A were measured with an ELISA.
      RESULTS: Activin A levels, expressed as median (95% CI) MoMs, were similar in the
      women with a normal-sized fetus and in those with a healthy small for gestational
      age fetus, 1.14 (95% CI 1.0-1.5) and 1.31 (95% CI 0.8-2.1), respectively (P =
      0.97). Compared to the women with a normal-sized fetus or a healthy small fetus,
      activin A levels were significantly elevated in the women who had an intrauterine
      fetal growth restriction fetus 2.37 (95% CI 1.6-3.7; P = 0.01 compared to normal
      and P = 0.04 compared to healthy small). CONCLUSIONS: These data confirm that
      circulating activin A is increased in association with fetal growth restriction.
      However, a single blood sample for activin A will not efficiently discern between
      healthy and compromised small fetuses.

PMID- 16638030
TI  - Subcutaneous sterile water injection for labour pain: a randomised controlled
      trial.
AB  - BACKGROUND: About 30% of women experience severe continuous low-back pain in
      labour, but limited options are available to reduce this pain especially in
      developing countries and remote areas. AIMS: To evaluate the efficacy of
      subcutaneous sterile water injection in reduction of labour pain compared with
      placebo. METHODS: One hundred (100) consecutive patients were enrolled in a
      double-blind randomised controlled trial. During the first stage of labour with
      planned normal vaginal delivery, the intervention group (n = 50) received 0.5 mL
      sterile water injected subcutaneously and the control group (n = 50) received
      normal saline as a placebo. Pain score was measured before and 10 and 45 min
      after the injection, using the faces rating scale. MAIN OUTCOME MEASURE: Low-back
      labour pain. RESULTS: The two groups were not significantly different regarding
      maternal age and weight, gestational age, parity and gravidity and degree of
      effacement. The median pain score was equal in both groups prior to the
      injection. Pain severity was reduced in both groups after the injection. However,
      the median pain score in the sterile water group was significantly lower than the
      placebo group 10 min (P < 0.01), as well as 45 min, after the injection (P <
      0.01). CONCLUSION: Administering one subcutaneous injection of sterile water in a
      painful point of the lumbosacral area is effective in reducing low-back pain
      during labour.

PMID- 16638031
TI  - A medical management of interstitial ectopic pregnancy: a 5-year clinical study.
AB  - BACKGROUND: Medical treatment of the rare interstitial ectopic pregnancy with
      methotrexate has been considered an alternative to surgical resection. AIM: To
      determine the treatment success rate with a single-dose intravenous
      methotrexate/folinic acid regimen and to identify predictors of treatment
      outcome. METHODS: A 5-year audit (April 2000-August 2005) was carried out,
      collecting clinical imaging data and serum beta-human chorionic gonadotrophin
      (beta-hCG). Time taken for complete beta-hCG resolution was recorded, and a
      negative beta-hCG result was used as an endpoint of successful outcome. RESULTS:
      Of the 13 cases, two required urgent surgery for rupture on presentation. In the
      remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic
      acid rescue (15 mg x 4 doses). There were no side-effects. Complete beta-hCG
      resolution was achieved in 10 of the 11 medically treated cases (91% success
      rate), requiring 21-129 days. Successful outcome was seen with initial beta-hCG
      level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live
      fetus. CONCLUSION: The methotrexate/folinic acid regimen used as a one-dose
      treatment is safe and effective for unruptured interstitial pregnancy, with no
      side-effects and the advantage of avoiding invasive surgery. Subsequent tubal
      patency and reproductive function are yet to be ascertained.

PMID- 16638032
TI  - Guidelines following hydatidiform mole: a reappraisal.
AB  - OBJECTIVE: The aim of this study was to determine how often patients with
      complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic
      gonadotrophin (hCG) levels subsequently develop persistent or recurrent
      gestational trophoblast disease. METHODS: Four hundred and fourteen cases of CHM
      registered at the Hydatidiform Mole Registry of Victoria were reviewed
      retrospectively after molar evacuation. Maternal age, gestational age, gravidity
      and parity were determined for each patient, as well as the need for
      chemotherapy. RESULTS: Among the 414 patients, 55 (13.3%) required chemotherapy
      for persistent trophoblastic disease. None of the patients whose hCG levels
      spontaneously fell to normal subsequently developed persistent molar disease.
      CONCLUSION: Weekly hCG measurements are recommended for all patients until normal
      levels are achieved. For patients who attain normal hCG levels within 2 months
      after evacuation, it seems safe to discontinue monitoring once normal levels are
      achieved. Patients who fail to achieve normal hCG levels by 2 months after
      evacuation should be monitored with monthly hCG measurements for 1 year after
      normalisation to assure sustained remission.

PMID- 16638033
TI  - Persistent trophoblast disease following partial molar pregnancy.
AB  - OBJECTIVE: Human chorionic gonadotrophin (hCG) follow-up data were analysed
      retrospectively in all patients registered in the Hydatidiform Mole Registry at
      the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to
      determine the risk of persistent trophoblast disease following partial molar
      pregnancy and to review the present follow-up protocol of patients suffering from
      partial hydatidiform molar pregnancy (PHM). METHODS: Demographic factors were
      determined for all 344 cases with a review diagnosis of PHM, included age,
      history of previous hydatidiform mole, gestation length, hCG levels and
      compliance with follow-up. FINDINGS: Six of the 344 patients diagnosed with PHM
      required treatment with single-agent methotrexate and folinic acid rescue. All
      six patients achieved and maintained a complete biochemical remission after
      chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients
      had at least one normal hCG measurement during follow-up, of whom 152 (64.7%)
      patients obtained normal values within 2 months after evacuation. All patients
      obtained normal levels within 32 weeks after evacuation of the partial
      hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up
      program. No patient who achieved normal hCG levels required chemotherapy because
      of a recurrent gestational trophoblastic tumour. RECOMMENDATIONS: This study
      indicates that 1.7% of all partial mole pregnancy patients needed treatment for
      malignant sequelae. In contrast, no patient diagnosed with partial mole had a
      biochemical or clinical relapse after achieving normal levels of hCG, consistent
      with previous studies. Patients who have had a partial hydatidiform mole should
      be followed by hCG assays until normal levels are achieved and then follow-up can
      be safely discontinued.

PMID- 16638034
TI  - Vacuum-assisted delivery: an analysis of traction force and maternal and neonatal
      outcomes.
AB  - Safety recommendations for vacuum-assisted delivery focus on limiting the number
      of pulls and the duration of the procedure. With the introduction of the Kiwi
      OmniCup vacuum extractor incorporating a Traction Force Indicator, it is now
      possible to reliably monitor and control the amount of traction force exerted on
      the fetal scalp. The OmniCup was used in a prospective observational study of 119
      vacuum-assisted deliveries in nulliparous women to establish practical guidelines
      for safe practice in typical clinical settings.

PMID- 16638035
TI  - Postmenopausal hormone therapy: who now takes it and do they differ from non
      users?
AB  - BACKGROUND: Considerable changes in hormone therapy use have taken place in the
      last few years. AIMS: To determine current usage of postmenopausal hormone
      therapy and assess the trend and rate of change in hormone therapy usage over the
      last 13 years. Additionally, to assess differences between current users and non
      users for health-related and risk factor variables. METHODS: Questions regarding
      hormone therapy use have been included in an annual face to face population
      health survey of South Australians eight times since 1991. In 2004, additional
      questions on health status and quality of life were included. RESULTS: In 2004,
      current use of hormone therapy was 15.4, 19.8 and 31.2% in all women over 40, 50
      and 50-59 years, respectively. Ever use of hormone therapy among all women over
      50 years was 46.5% with a mean duration of use of 7.46 years. Hormone therapy
      users did not differ from non-users in chronic disease indicators, body mass
      index, complementary medicine or therapist use, other health service use,
      socioeconomic status or quality of life. Increased hormone therapy use was
      associated with higher income, better educated, employed and married women in
      their sixth decade. Current use has varied over the years, with an increase to
      2000, but a drop in 2003 and 2004. CONCLUSION: Apart from menopausal symptoms,
      there is no evidence to support differences between users and non-users in terms
      of quality of life or health characteristics, requiring more appropriate
      selection of women for hormone therapy.

PMID- 16638036
TI  - Effect of inhaled glucocorticoid treatment on placental 11beta-hydroxysteroid
      dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated
      by asthma.
AB  - BACKGROUND: Asthma is a common disease affecting 12% of Australian women with 55%
      of women experiencing at least one exacerbation during pregnancy. Exacerbations
      during pregnancy are associated with low birthweight neonates and stillbirth. One
      of the main reasons for maternal exacerbations during pregnancy is non-compliance
      with inhaled glucocorticoid treatment due to the misconception that inhaled
      glucocorticoids are harmful to the fetus. AIMS AND METHODS: We have therefore
      assessed whether the commonly used inhaled glucocorticoids reduce placental
      glucocorticoid metabolising capacity, by measuring 11beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD-2) activity. As these treatments potentially
      increase the exposure of the fetus to the growth-inhibiting effects of
      glucocorticoids, we also examined the question of whether inhaled glucocorticoid
      use was associated with reduced birthweight. Pregnant women using budesonide (n =
      18), fluticasone propionate alone (n = 14) and fluticasone propionate in
      combination with the long-acting beta2 agonist salmeterol (n = 9) were compared
      to a non-asthmatic control group (n = 20). RESULTS: The use of inhaled budesonide
      was associated with significantly increased placental 11beta-HSD-2 activity
      relative to the control group. Inhaled glucocorticoid use for the treatment of
      asthma was associated with normal birthweight. In the small number of women using
      combination therapy (fluticasone and salmeterol), there was reduced birthweight
      compared to the control group. CONCLUSION: Inhaled glucocorticoids alone do not
      adversely affect fetal growth and placental function.

PMID- 16638037
TI  - No more surrogate end-points in randomised trials: the PCOSMIC trial protocol for
      women with polycystic ovary syndrome using metformin for infertility with
      clomiphene.
AB  - Current data supporting the effectiveness of metformin as a fertility treatment
      for women with polycystic ovary syndrome have been misinterpreted. Still unproven
      for women with polycystic ovary syndrome is, first, whether metformin adds to the
      standard first-line fertility management in all women, second, whether metformin
      is an effective fertility treatment for overweight women, and third, the relative
      fertility efficacy of metformin and clomiphene citrate as a first-line treatment
      in women with a lower body weight. The PCOSMIC (polycystic ovary syndrome:
      metformin for infertility with clomiphene) trial is an ongoing New Zealand
      multicentre double-blind placebo-controlled parallel randomised trial assessing
      these questions.

PMID- 16638038
TI  - Activin A, hypoxia and the prediction of obstetric outcomes.
AB  - On the back of sheep experiments showing that uterine hypoxia induces a rapid and
      sustained elevation of fetal activin A levels, we undertook two prospective
      studies to explore whether this novel observation could be exploited clinically.
      The first was a prospective labour ward study investigating whether umbilical
      arterial activin A levels at delivery correlated with either neonatal hypoxic
      ischaemic encephalopathy or pH. Unfortunately, we were unable to demonstrate a
      link with either, but found that levels were significantly depressed among those
      who had an emergency Caesarean section, suggesting a possible role in active
      labour. Second, we investigated the link between activin A and intrauterine
      growth restriction (IUGR), a condition of fetoplacental hypoxia, by measuring
      levels in women presenting for antenatal ultrasound biometry with clinical
      suspicion of a small baby. We found that, compared to pregnancies with a baby
      that was small for gestational age (SGA) but otherwise healthy, levels were 2.4
      and 8 times higher, respectively, in pregnancies complicated by IUGR, and those
      complicated by both IUGR and preeclampsia. However, a single blood sample of
      activin A was unable to distinguish between IUGR and SGA pregnancies with
      sufficient sensitivity to be clinically useful. Our studies were unable to
      demonstrate clinical utility for the experimental observation linking activin A
      and hypoxia.

PMID- 16638039
TI  - Activin-A secretion is increased in the eutopic endometrium from women with
      endometriosis.
AB  - BACKGROUND: Activin is a well-characterised growth and differentiation factor and
      an important inflammatory mediator. Activin is secreted by normal endometrial
      glands and stroma and is expressed by endometrial leucocytes. It is also known
      that the eutopic endometrium from women with endometriosis is functionally
      different to that from women without endometriosis. In this study, we hypothesise
      that the endometrial secretion of activin is altered in women with endometriosis.
      AIMS: To determine whether the expression of inhibin/activin subunits and the
      secretion of activin-A is different in eutopic endometrium from women with and
      without endometriosis. METHODS: Endometrial biopsies were obtained from
      premenopausal, regularly menstruating women with and without endometriosis.
      Staining intensity for the different inhibin/activin subunits was compared in
      endometrial and endometriotic biopsies. Activin-A secretion was studied using
      endometrial explants and endometrial glandular and stromal monolayer cell
      cultures. RESULTS: The alpha- and betaA-subunits of inhibin/activin were more
      abundant in eutopic glandular cells from patients with minimal to mild
      endometriosis compared to women without endometriosis. In patients with
      endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and
      endometrial leucocytes. Comparison of paired endometrial and endometriotic
      biopsies from the same patient did not reveal significant differences for any of
      the inhibin/activin subunits or activin receptors. Activin-A secretion by
      glandular and stromal endometrial cells was sevenfold and threefold higher,
      respectively, in women with endometriosis compared to women without
      endometriosis. CONCLUSIONS: The expression of inhibin/activin subunits in eutopic
      endometrium is altered in women with endometriosis, leading to higher levels of
      activin-A secretion by both glandular cells and stromal cells.

PMID- 16638040
TI  - Molecular profiling of human endometrium during the menstrual cycle.
AB  - This summary of the findings of investigations of the changing transcriptional
      profile of human endometrium during the menstrual cycle shows that it is possible
      to classify the menstrual cycle based on the global gene expression profile, and
      identifies groups of known and novel genes that may be associated with different
      biological processes that occur in the endometrium such as implantation and
      menstruation.

PMID- 16638041
TI  - A possible role for progesterone metabolites in human parturition.
AB  - There has been a recent resurgence of interest in the role of progesterone in the
      maintenance of human pregnancy and the onset of labour, following recent reports
      of its use to prevent preterm labour in high-risk patients. One possible
      mechanism by which progesterone might contribute to uterine quiescence is through
      the actions of its metabolites. This article provides a brief overview of
      progesterone in human pregnancy and an outline of progesterone metabolism in the
      various reproductive tract tissues as well as the evidence for actions of
      progesterone metabolites in pregnancy.

PMID- 16638042
TI  - Do women with polycystic ovary syndrome really have predisposition to
      atherosclerosis?
AB  - The elastic properties of the aorta were studied in 28 women with polycystic
      ovary syndrome (PCOS) and in 26 regularly menstruating healthy women. In PCOS and
      control groups, systolic and diastolic blood pressure, aortic systolic diameter,
      aortic diastolic diameter, aortic distensibility, aortic stiffness index, and
      aortic elastic modulus were similar. It is likely that PCOS does not have any
      innate adverse effects on the cardiovascular system if its undesirable metabolic
      consequences are successfully controlled.

PMID- 16638043
TI  - Successful pregnancy in a woman with glycogen storage disease type III.

PMID- 16638044
TI  - Re: Effects of rosiglitazone on hormonal profile and ovulatory function in
      Chinese women with polycystic ovary syndrome.

PMID- 16638046
TI  - Re: Comparison of cerebral magnetic resonance and electroencephalogram findings
      in preeclamptic and eclamptic women.

PMID- 16638047
TI  - Re: Customised fetal weight: centile charts or tables?

PMID- 16638048
TI  - Re: Factors associated with low immunity to rubella infection on antenatal
      screening.

PMID- 16638051
TI  - Re: Midurethral Tissue Fixation System sling--a 'micromethod' for cure of stress
      incontinence--preliminary report and Tissue Fixation System posterior sling for
      repair of uterine/vault prolapse--a preliminary report.

PMID- 16638052
TI  - Re: Total reconstruction.

PMID- 16638054
TI  - Re: Tissue Fixation System (TFS).

PMID- 16638056
TI  - Re: Midurethral Tissue Fixation System (TFS).

PMID- 16638058
TI  - [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid].
AB  - Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite
      the fact that only few randomized trials have been published, BPO is considered
      the standard in topical acne treatment. Anaerobic bacteria are reduced by
      oxidative mechanisms and the induction of resistant strains is reduced. Topical
      formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect
      is dose-dependent, but the irritation increases with higher concentrations.
      Usually 5 % BPO is sufficient to control acne grade I-II. Due to its strong
      oxidative potential, patients should be advised that BPO may bleach colored and
      dark clothing, bedding and even hair. BPO is safe for use in pregnant and
      lactating females because it is degraded to benzoic acid. It is a cost-effective
      treatment for acne grade I-II. Patients with papulopustular acne grade I-II,
      particularly with marked inflammation, show satisfactory improvement with topical
      antibiotic treatment. The following compounds are available and effective:
      erythromycin, clindamycin and tetracycline (the latter being less frequently
      used). A review in 1990 suggested that topical tetracycline was ineffective in
      the treatment of acne. Along with eliminating Propionibacterium acnes, the main
      mechanism of topical antibiotics is their antiinflammatory effect. All three
      penetrate the epidermal barrier well and are similarly efficacious. Randomized
      trials have shown that in concentrations of 2-4 %, their effects are comparable
      to oral tetracycline and minocycline. Combination therapy with retinoids or
      benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and
      reduce comedones, while topical antibiotics primarily address inflammation. One
      side effect of topical antibacterial treatment is an increase in drug-resistant
      resident skin flora with gram-negative microorganisms prevailing, which can lead
      to gram-negative folliculitis. All three antibiotics fluoresce under black light
      which may produce interesting effects in a discotheque. There are two reports of
      topical clindamycin causing pseudomembranous colitis after long-term and
      widespread usage. Azelaic acid has a predominant antibacterial action, although
      it is not considered as an antibiotic in the classical sense. Furthermore, it
      possesses a modest comedolytic effect. Burning upon application is common. Since
      azelaic acid is naturally present, systemic side effects are not likely to occur,
      making it safe for acne treatment during pregnancy and lactation.

PMID- 16638059
TI  - [Post-marketing surveillance on treatment of 5,665 patients with atopic
      dermatitis using the calcineurin inhibitor pimecrolimus: positive effects on
      major symptoms of atopic dermatitis and on quality of life].
AB  - BACKGROUND: Topical application of the calcineurin inhibitors pimecrolimus and
      tacrolimus is a current major advance in the therapy of atopic dermatitis. The
      aims of this post-marketing surveillance were: a) to acquire data on the efficacy
      and tolerability of pimecrolimus ointment (Elidel) on a very large cohort of
      patients from outpatient clinics, and b) to assess changes in their quality of
      life, a parameter not often considered in previous studies. PATIENTS AND METHODS:
      Included were 5,665 patients with atopic dermatitis. During the observation
      period, data on efficacy and tolerability were obtained at the beginning of the
      study, 3 to 10 days after initiation of therapy and after 4 to 6 weeks.
      Evaluation of symptoms as well as assessment of efficacy and tolerability were
      based on linear scales and on the percentage of the body surface area (% BSA)
      involved. Quality of life was assessed by the German version of the "Dermatology
      Life Quality Index (DLQI)" or the "Children's Dermatology Life Quality Index
      (CDLQI)". RESULTS: In this largest post-marketing surveillance hitherto performed
      in Germany, the efficacy of pimecrolimus was judged as "good" by 79.3 % of
      physicians and by 76.5 % of patients. Tolerability was assessed as "good" by 87.2
      % of physicians and by 83.1 % of patients. Major symptoms of atopic dermatitis
      such as pruritus, erythema or lichenification showed marked reduction after just
      3 to 10 days, signalling general improvement of the skin disease. In addition,
      application of pimecrolimus resulted in a significant improvement of the quality
      of life scores in both children and adults. CONCLUSION: The present study
      demonstrates that the good efficacy and tolerability of pimecrolimus ointment
      which had been shown in controlled trials: i) could also be demonstrated on a
      very large cohort of patients with atopic dermatitis when used in the outpatient
      setting, and ii) were paralleled by a significant improvement in the quality of
      life.

PMID- 16638060
TI  - [Ehlers-Danlos syndrome--20 years experience with diagnosis and classification at
      the university skin clinic of Heidelberg].
AB  - BACKGROUND: The Ehlers-Danlos syndrome encompasses a group of hereditary
      disorders of the connective tissue, characterized by hyperextensible skin, joint
      hypermobility; and varying degrees of vessel and tissue fragility. The main forms
      are classical, hypermobile, vascular, kyphoscoliotic A/B, arthrochalasis A/B and
      dermatosparaxis types. PATIENTS AND METHODS: We report our experience in
      diagnosis and classification of Ehlers-Danlos-syndrome, especially with the
      combination of clinical and morphological criteria, at the Department of
      Dermatology of the University of Heidelberg with more than 600 patients between
      1984 and 2004. RESULTS: We classified those types of EDS which are characterized
      by regular and characteristic ultrastructural changes in the dermal components,
      primarily collagen, including the classical, hypermobile and vascular types as
      well as the less-common arthrochalasis and dermatosparaxis types. The combination
      of clinical and morphologic features facilitates the selection of candidate genes
      for molecular genetic investigation. CONCLUSIONS: Besides the skin, skeleton and
      vessels, many other organ systems such as eyes and intestine, can be affected in
      Ehlers-Danlos syndrome. Accordingly, interdisciplinary cooperation (pediatrics,
      surgery, orthopedics, rheumatology, neurology, genetics) is necessary. As the
      connective tissue of the skin is accessible for biopsy and diagnostic
      investigation, dermatologists should be trained in the diagnostic approach and
      classification of this syndrome.

PMID- 16638061
TI  - [Keratosis pilaris and keratosis pilaris atrophicans faciei].
AB  - Keratosis pilaris and ulerythema ophryogenes (keratosis pilaris atrophicans
      faciei) are hereditary disorders with altered follicular keratinization that show
      follicular, horny papules surrounded by an erythematous halo. Ulerythema
      ophryogenes is an uncommon variant of keratosis pilaris characterized by
      erythematous follicular papules of the eyebrows and cheeks followed by a gradual
      loss of hair. On the background of 15-year-old boy who presented with keratosis
      pilaris and ulerythema ophryogenes, we discuss the various clinical
      manifestations of keratosis pilaris.

PMID- 16638062
TI  - [Skin ulceration after leflunomide treatment in two patients with rheumatoid
      arthritis].
AB  - Leflunomide is a disease-modifying antirheumatic drug for the treatment of active
      rheumatoid arthritis and psoriatic arthritis. Skin ulcerations are not listed as
      a side effect for this drug, and there has been only one case report on
      leflunomide associated skin ulcerations. We report on two females, 59 and 63
      years old respectively, who were treated with leflunomide for rheumatoid
      arthritis and subsequently developed severe skin ulcerations. After
      discontinuation of the drug the skin ulcerations healed complete even if very
      slowly.

PMID- 16638063
TI  - [Candida albicans--interactions with the mucosa and the immune system].

PMID- 16638064
TI  - [Diagnostic quiz: pruritus and papules].

PMID- 16638065
TI  - [Brief guidelines: malignant melanoma of the skin].

PMID- 16638066
TI  - [Diagnostic and therapeutic procedures in chronic pruritus].

PMID- 16638068
TI  - The relation of stress and psychiatric illnesses to coronary heart disease.

PMID- 16638069
TI  - Smoldering systemic inflammation: a link between schizophrenia, smoking and
      obesity.

PMID- 16638070
TI  - Prospective investigations of the prodromal state of schizophrenia: review of
      studies.
AB  - OBJECTIVE: The paper presents a comprehensive overview of prospective studies
      monitoring or intervening in the pre-onset phase of first episode psychosis.
      METHOD: A systematic literature search was conducted and supplemented by a manual
      search. All relevant studies were ordered and intensively reviewed according to
      specified criteria. Methodological and conceptual issues are discussed. RESULTS:
      Reports of 23 prospective studies were found, some describing subsamples of
      larger samples. Major methodological and conceptual divergences exist.
      CONCLUSION: Applied criteria detect individuals with a significantly increased
      risk of psychosis within the schizophrenia spectrum, but these criteria are only
      validated on clinical populations. The significance of differences in sample
      characteristics is unclear. Most study samples are small. Results are preliminary
      and in need of further research before they constitute a realistic knowledge
      base. Methodological and conceptual issues should not be underestimated.

PMID- 16638071
TI  - Prospective investigations of the prodromal state of schizophrenia: assessment
      instruments.
AB  - OBJECTIVE: To review assessment instruments used for detection of prodromal or at
      risk mental states, and discuss their role in current research. METHOD: A
      systematic electronic literature search was conducted and supplemented by a
      manual search. All relevant scales were selected for the purpose of the review.
      RESULTS: Six interviews and four screening instruments were found. Two main
      traditions are prevailing: the Attenuated Positive Symptoms approach and the
      Basic Symptoms approach. Reports of psychometric properties of the interviews are
      preliminary. CONCLUSION: The instruments detect individuals with an increased
      risk of psychosis in clinical populations, but predictive validity and measures
      of reliability is insufficiently evaluated. Studies including instruments from
      both traditions should be conducted, in order to obtain an empirical basis of
      hypothesized relations between instruments. Instruments elucidating
      phenomenological aspects of anomalies in self-experience may contribute with
      valuable data on the pre-onset phase of psychosis.

PMID- 16638072
TI  - Alcohol abuse partly mediates the association between coronary heart disease and
      affective or psychotic disorders: a follow-up study in Sweden.
AB  - OBJECTIVE: To analyse whether hospitalization for affective or psychotic
      disorders predicts coronary heart disease (CHD) after accounting for occupation,
      region and alcohol-related disorders. METHOD: National registers were used to
      identify all individuals in Sweden aged 25-64 years at first hospitalization for
      affective or psychotic disorders and aged 25-79 years at first hospitalization
      for CHD between 1987 and 2001. Standardized incidence ratios (SIRs) were
      calculated. RESULTS: The association between CHD and affective or psychotic
      disorders was strongest in the youngest age groups. The overall SIRs varied
      between 1.39 and 1.68. They were strongly attenuated but remained significant
      after adjustment for hospitalization because of alcohol-related disorders,
      especially among women. CONCLUSION: Hospitalization because of affective or
      psychotic disorders predicts CHD. These associations are partly mediated by
      alcohol abuse. Clinicians and decision makers should be aware of the increased
      risk of CHD in these patient groups.

PMID- 16638073
TI  - Depression assessed over 1-year survival in patients with myocardial infarction.
AB  - OBJECTIVE: To estimate the prevalence of ICD-10 depression using a self-reported
      questionnaire and to examine if depression is associated with increased 1-year
      mortality in patients with myocardial infarction (MI). METHOD: In total, 763 MI
      patients completed the Major Depression Inventory at discharge. Information from
      hospital notes was collected and patients were followed 1 year for re-admission
      and mortality through national registries. RESULTS: Seventy-three patients (9.6%)
      were depressed at discharge. Depression was not a significant independent
      predictor of mortality; however, there was a significant trend for increasing
      mortality with increasing severity of the depressive state (P = 0.028). All
      mortality among depressed patients was in patients with non-Q-wave infarction.
      CONCLUSION: Ten per cent of MI-patients fulfilled diagnostic criteria for
      depression at discharge. There was a significant trend for increasing mortality
      with increasing severity of the depressive episode. All mortality among depressed
      patients was seen in patients with non-Q-wave infarction. These findings indicate
      future studies in selected subgroups of MI-patients.

PMID- 16638074
TI  - The cardiovascular and respiratory health of people with schizophrenia.
AB  - OBJECTIVE: To examine the cardiovascular and respiratory health of people with
      severe mental illness (SMI) and compare findings with the Health Surveys for
      England. METHOD: A prospective, multi-centre observational prevalence study of
      602 patients with schizophrenia-related psychoses carried out in six locations
      across the UK over 24 months. RESULTS: Compared with general population subjects,
      people with SMI reported higher rates of angina and respiratory symptoms and had
      poor lung function. Much of this increased risk could be explained by lifestyle
      risk factors; there were increased levels of obesity among younger people with
      SMI. CONCLUSION: Key indicators of the cardiovascular and respiratory health of
      people with SMI are poor compared with those of the general population. Care
      plans should prioritize interventions to attenuate lifestyle risk factors.
      Evidence of increasing obesity in younger patients is of particular concern,
      predicting even greater health needs in the future.

PMID- 16638075
TI  - Obesity among individuals with serious mental illness.
AB  - OBJECTIVE: To study the distribution and correlates of body mass index (BMI)
      among individuals with serious mental illness. METHOD: A total of 169
      participants were recruited from randomly selected out-patients receiving
      community-based psychiatric care and were interviewed with items from the
      National Health and Nutrition Examination Survey (NHANES) III. Their BMI was
      compared with that of 2404 matched individuals from the NHANES data set. RESULTS:
      The distribution of BMI in the psychiatric sample significantly differed from
      that of the comparison group; 50% of women and 41% of men were obese compared
      with 27% and 20% in the comparison group. Within the psychiatric sample, higher
      BMI was associated with current hypertension and diabetes, a wish to weigh less,
      and reduced health-related functioning. CONCLUSION: Obesity is more prevalent
      among individuals with serious mental illness than in demographically matched
      individuals from the US general population. Among persons with mental illness,
      obesity is associated with co-occurring health problems.

PMID- 16638076
TI  - Association analyses of the neuregulin 1 gene with schizophrenia and manic
      psychosis in a Hispanic population.
AB  - OBJECTIVE: This study used the population of the Central Valley of Costa Rica
      (CVCR) and phenotyping strategies alternative to DSMIV classifications to
      investigate the association of neuregulin 1 with schizophrenia. METHOD: Using 134
      family trios with a history of psychosis, we genotyped six of the seven markers
      originally identified to be associated with schizophrenia in Iceland. RESULTS:
      The neuregulin Icelandic haplotype was not associated with schizophrenia in the
      CVCR population. However, a novel haplotype was found to be overrepresented in
      subjects with functional psychosis (global P-value > 0.05). Stratification of the
      sample by history of mania suggests that this haplotype may be preferentially
      over-transmitted to persons with a history of manic psychosis. CONCLUSION: These
      results suggest that the neuregulin 1 gene is unlikely to play a major role in
      predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other
      Latin American populations should be performed in order to corroborate these
      findings.

PMID- 16638077
TI  - Positive symptoms and duration of illness predict functional laterality and
      attention modulation in schizophrenia.
AB  - OBJECTIVE: Dichotic listening (DL) performance in schizophrenia, reflecting
      hemispheric asymmetry and the functional integrity of the left temporal lobe, can
      vary with clinical characteristics. Previous studies have not taken the co
      linearity of clinical variables into account. The aim of the present study was to
      evaluate the roles of positive symptoms and duration of illness in DL through
      Structural Equation Modeling (SEM), thus allowing for complex relationships
      between the variables. METHOD: We pooled patients from four previous DL studies
      to create a heterogeneous group of 129 schizophrenic patients, all tested with a
      consonant-vowel syllables DL procedure that included attentional instructions.
      RESULTS: A model where positive symptoms predicted a laterality component and
      duration of illness predicted an attention component in DL was confirmed.
      CONCLUSION: Positive symptoms predicted reduced functional laterality, suggesting
      involvement of left temporal lobe language processing. Duration of illness
      predicted impaired attention modulation, possibly reflecting the involvement of
      frontotemporal networks.

PMID- 16638078
TI  - Treatment delay and response rate in first episode psychosis.
AB  - OBJECTIVE: There is no consistent evidence of long duration of untreated
      psychosis (DUP) predicting long time to response (TTR) in first psychosis. This
      study aims to investigate the predictors of DUP and TTR in a first episode
      patient population. METHOD: An epidemiologically representative sample of 157 non
      affective first psychotic episode patients was interviewed and followed-up for at
      least half a year. RESULTS: The mean DUP was 46 weeks, the median 31 days. Long
      DUP was associated with being unemployed before treatment and male gender. Short
      DUP, having a job, and living with a partner before treatment predicted early
      response. CONCLUSION: Early intervention likely improves short-term treatment
      response in first episode psychosis. The best strategy to reduce DUP probably is
      to direct attention to the substantial number of patients who do not engage in
      regular treatment.

PMID- 16638079
TI  - Pattern of health service utilization and predictors of readmission after a first
      admission for psychosis: a 2-year follow-up study.
AB  - OBJECTIVE: To explore the pattern of health service utilization over 2 years
      following a first admission for psychosis and the baseline characteristics
      predicting readmission. METHOD: Patients included in a cohort of first-admitted
      subjects with psychosis (n = 84) were assessed at the end of a 2-year follow-up
      using multiple sources of information. RESULTS: At the end of the follow-up, one
      of three subjects had no contact with any mental health professional, and 38% of
      subjects had no contact with a psychiatrist. Half of the patients were readmitted
      over the 2-year follow-up. The baseline characteristics independently predicting
      psychiatric readmission were a high number of helping contacts before first
      admission and persistence of psychotic symptoms at discharge. CONCLUSION:
      Decreasing the frequency of readmission in the early course of psychosis is a
      public health priority. Development of psychotherapeutic programs for subjects
      with early psychosis who have enduring psychotic symptoms at first discharge
      should be promoted.

PMID- 16638080
TI  - Neuropsychological test profiles in schizophrenia and non-psychotic depression.
AB  - OBJECTIVE: The study examined to what degree schizophrenia is characterized by a
      neuropsychological (NP) test profile specific in shape and level compared with
      depression and normal functioning. METHOD: Fifty-three patients with
      schizophrenia, 45 with non-psychotic depression, and 50 normals were assessed
      with a comprehensive NP test battery and clinical instruments. NP test scores
      were factor analyzed into seven composite scores. RESULTS: Schizophrenia patients
      performed significantly below normals across all seven composite scores, whereas
      depression patients were impaired in two. Verbal memory was most impaired. Sixty
      two percent of schizophrenia patients were moderately or severely impaired, the
      corresponding figure for depression was 28%. Impairment was moderately associated
      with IQ level and clinical symptom load in schizophrenia, but not in depression.
      CONCLUSION: Schizophrenia is characterized by deficits across a wide range of NP
      functions. Thirty-eight percent of the patients are within normal limits. A mild
      and limited NP disturbance is apparent in depression.

PMID- 16638081
TI  - Post-traumatic stress disorder and amygdala-hippocampectomy.
AB  - OBJECTIVE: The case report suggests the indispensability of preoperative accurate
      psychiatric checkups especially in temporal resections. METHOD: A single case was
      reported. RESULTS: We report the case of a 20-year-old woman suffering for 12
      years from primary generalized epilepsy, attributed to left-sided hippocampal
      sclerosis. Because seizures were resistant to drug therapy, she underwent
      amygdala-hippocampectomy at the age of 18. Furthermore, she had previously been
      victim of childhood sexual abuse. Two weeks after epilepsy surgery, she
      manifested symptoms of post-traumatic stress disorder (PTSD). CONCLUSION: There
      is evidence that the amygdala-hippocampal region is both functionally and
      morphologically involved in the aetiology of PTSD. The removal of this marked
      neuroanatomical region and the resulting disconnection and asymmetry between
      right and left amygdala-hippocampal region might be seen as an evidence for this
      region aetiologically being involved in the patient's PTSD symptoms.

PMID- 16638088
TI  - Pegylated interferon for treatment in hemodialysis patients with chronic
      hepatitis C.

PMID- 16638089
TI  - Enteroliths developed in a chronically obstructed afferent loop coexisting with
      gastric remnant carcinoma: Case report and review of the literature.
AB  - A case of gastric remnant carcinoma coexisting with a chronic afferent loop
      syndrome harboring multiple enteroliths in a grossly dilated and elongated
      afferent loop is presented herein. The patient had undergone a Polya type
      antecolic Billroth II reconstruction for a stenosing duodenal ulcer 40 years
      previously. A concise review of the relevant literature is also presented.

PMID- 16638090
TI  - Childhood pancreatitis.
AB  - Inflammation of the pancreas has many presentations in children and adolescents.
      The etiology is often elusive, with a great number of cases being idiopathic.
      However, there have been a number of recent advances in the areas of cell
      biology, genetics and imaging technology, which should be highlighted. Herein is
      provided a review for the reader with particular emphasis on some of these newer
      advances.

PMID- 16638091
TI  - Evaluation of gastrointestinal motility by computerized analysis of abdominal
      auscultation findings.
AB  - BACKGROUND AND AIMS: To evaluate gastrointestinal motility by abdominal
      auscultation. METHODS: Abdominal auscultated sounds of 20 healthy adults and 10
      diabetes mellitus patients with delayed gastric emptying were digitally recorded
      and then analyzed by computer while simultaneously monitoring the motility of the
      antrum of the stomach by ultrasonography. The auscultated sound, when the stomach
      wall was moving, was regarded as the gastroduodenal (GD) sound and when not
      moving as the intestinal (I) sound. The sound index (SI; the sum of the
      amplitude) was calculated to indicate the power of sound. Sounds were recorded
      for 15 min under fasting conditions and 60 min after a liquid meal. In six
      healthy adults, the gastroduodenal pressure was recorded under abdominal
      auscultation to detect any correlation between the motility index (MI; the sum of
      the area under the curve) and SI. RESULTS: A definite increase in the SI of the
      GD sound was observed after the liquid meal in comparison with that of the I
      sound. A positive correlation (r = 0.678) was observed between the SI of the GD
      sound and MI, thus, it was considered that the GD sound reflected the motility of
      the gastroduodenal wall. In the diabetes mellitus patients, the SI of the GD
      sound was significantly lower after food intake than in healthy adults.
      CONCLUSION: The results of the present study indicate that the abdominal
      auscultation test could be used as a new diagnostic method to detect any
      abnormality in gastrointestinal motility.

PMID- 16638092
TI  - Dyspeptic symptoms associated with hypersensitivity to gastric distension induced
      by duodenal acidification.
AB  - BACKGROUND AND AIM: Duodenal acidification might increase sensitivity to gastric
      distension, which seems to play a role in the genesis of dyspeptic symptoms in a
      subset of patients with functional dyspepsia. The aim of the present study was to
      investigate the characteristics of dyspeptic symptoms associated with
      hypersensitivity to gastric distension induced by duodenal acidification.
      METHODS: An infusion tube and a barostat bag were positioned in the duodenum and
      gastric fundus, respectively. Sensitivity to stepwise fundic distensions with
      severity scoring of the seven dyspeptic symptoms was assessed before and during
      duodenal acid infusion in 20 healthy subjects. RESULTS: Acid infusion
      significantly decreased the pressures and the corresponding wall tensions at the
      thresholds for discomfort. At the distending level of minimal distending pressure
      (MDP) + 2 mmHg, significantly higher scores of fullness and bloating were
      obtained during acid infusion. With distending stimuli of MDP + 4 and 6 mmHg,
      fullness, bloating, nausea, satiety, epigastric burning and epigastric pain were
      significantly more severe during acid infusion than before acid infusion. At the
      level of MDP + 8 mmHg, the severity of epigastric pain was significantly greater,
      compared with that before acid infusion. CONCLUSIONS: Duodenal acidification
      might aggravate dyspeptic symptoms through the induction of hypersensitivity to
      gastric distension in healthy individuals. Those symptoms are diverse and
      variable, depending on the strength of the distending stimuli.

PMID- 16638093
TI  - Rotavirus double-stranded RNA induces apoptosis and diminishes wound repair in
      rat intestinal epithelial cells.
AB  - BACKGROUND: Recent studies have shown that toll-like receptor 3 (TLR3) recognizes
      double-stranded RNA (dsRNA). Rotaviruses, having a dsRNA genome, infect
      intestinal epithelial cells (IEC) and cause acute gastroenteritis in young
      children. The aim of the present study was to clarify the pathophysiological
      function of rotavirus dsRNA in IEC. METHODS: Expression of TLR3 mRNA or protein
      in IEC cell lines (IEC-6, HT-29, Caco-2) was assessed by reverse transcription
      polymerase chain reaction (RT-PCR), Western blot analysis or
      immunohistochemistry. Induction of cytokines (TNF-alpha, interferon-beta,
      interleukin-6) mRNA and activation of signal proteins (ERK1/2 MAPK and IkappaB
      alpha) in IEC after stimulation with rotavirus dsRNA were assessed by RT-PCR or
      Western blot analysis. IEC-6 cells were wounded and cell migration into wound
      areas after stimulation with rotavirus dsRNA (1-25 microg/mL) was assessed.
      Induction of apoptosis after stimulation with rotavirus dsRNA was also assessed.
      RESULTS: Expression of TLR3 mRNA and TLR3 protein was detected in IEC. Expression
      of TLR3 mRNA in IEC-6 tended to be up-regulated by exposure to IFN-gamma.
      Induction of cytokine mRNA and activation of the signal proteins were detected
      after stimulation with rotavirus dsRNA. Apoptosis was induced and epithelial
      migration into the wound area was dose-dependently diminished (44.1-94.4%, P <
      0.01) by exposure to rotavirus dsRNA. Diminishment of wound repair was suppressed
      by anti-TLR3 antibody or caspase inhibitor. CONCLUSION: Rotavirus dsRNA induces
      severe apoptosis and diminishes wound repair in IEC through TLR3, which might be
      involved in the pathogenesis of rotavirus-induced enteritis.

PMID- 16638094
TI  - Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and
      leucovorin in advanced pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is a dismal disease. Few drugs, including
      gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against
      advanced pancreatic cancer. The purpose of the present study was to determine the
      maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of
      weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer.
      METHODS: Patients with histo-/cytologically confirmed, advanced pancreatic cancer
      were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800
      mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1,
      day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5
      FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed
      MTD for subsequent enrolled patients. RESULTS: Eighteen patients were enrolled in
      the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major
      dose-limiting toxicities being febrile neutropenia and delayed recovery from
      neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU
      dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients,
      myelosuppression was the main toxicity, with grade 3 neutropenia in eight
      patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat
      analysis, the overall and clinical benefit response rates were 22% and 46%,
      respectively; with median progression-free and overall survival of 4.1 and 6.9
      months, respectively. CONCLUSIONS: The GemFL24 regimen is a feasible and
      moderately active treatment with manageable toxicities for advanced pancreatic
      cancer, and could be a basis for further combination with other anticancer drugs.

PMID- 16638095
TI  - Xanthine oxidase-derived free radicals directly activate rat pancreatic stellate
      cells.
AB  - BACKGROUND AND AIM: Free radicals are reported to be associated with fibrosis in
      the pancreas. It is generally accepted that pancreatic stellate cells (PSC) play
      an important role in pancreatic fibrosis. However, the exact role of free
      radicals in activation of PSC has not been fully elucidated. In the present
      study, using a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC)
      with cultured PSC, we investigated how free radicals act on the activation of
      PSC. METHODS: PSC were isolated from male Wister rats. Cultured rat PSC were
      incubated with DDC for 48 h. Intracellular SOD activity and lipid peroxidation
      were examined in DDC-treated PSC. Activation of PSC was examined by determining
      the expression of alpha-smooth muscle actin (alpha-SMA) by immunocytochemistry.
      The number of PSC using a hemocytometer, type I collagen secretion with ELISA and
      matrix metalloproteinases (MMP) activities with gelatin zymography were also
      examined. Secretion of transforming growth factor-beta1 (TGF-beta1) was evaluated
      by ELISA. The effects of the allopurinol, a xanthine oxidase (XOD) inhibitor, on
      PSC were also examined. RESULTS: DDC decreased SOD activity and increased lipid
      peroxidation products in PSC. DDC activated PSC, increasing the number of alpha
      SMA positive cells, enhancing secretion of type I collagen and MMP, inhibiting
      PSC proliferation. Secretion of TGF-beta1, which is known to activate PSC, was
      increased by DDC treatment. These alterations were prevented by allopurinol.
      CONCLUSION: These results suggest that free radicals generated by XOD might
      directly activate PSC.

PMID- 16638096
TI  - Severity of atrophic gastritis related to antiparietal cell antibody and gastric
      carcinogenesis, including p53 mutations.
AB  - BACKGROUND AND AIMS: Infection with Helicobacter pylori (Hp) has been linked to
      atrophic gastritis, an inflammatory precursor of non-cardia gastric carcinoma.
      Mutations in the p53 gene are one of the most frequent genetic alterations in
      gastric carcinoma. In a subgroup of atrophic gastritis, antiparietal cell
      antibody (APCA) has been detected. This study was aimed to clarify the role of
      APCA in the progression of atrophic gastritis and gastric carcinogenesis, and to
      determine the relationship of the severity of atrophic gastritis to gastric
      carcinoma and to p53 mutations. METHODS: In 494 control subjects and 284 gastric
      carcinoma patients, serum APCA was evaluated and all subjects and patients were
      classified into four groups using serologic markers (anti-Hp IgG antibody and
      pepsinogen (PG) test: positive; PG I < 70 microg/L and PG I/II ratio < 3.0) as
      follows: A, HP- PG-; B, HP+ PG-; C, HP+ PG+ and D, HP- PG+. p53 mutations were
      analyzed in 174 of 284 patients. RESULTS: Antiparietal cell antibody
      seropositivity increased from group B to D, however, no difference in its
      positivity was found between controls and patients. The incidence of gastric
      carcinoma increased from A to D, especially the intestinal subtype. The frequency
      of p53 gene mutations was higher in PG+ than in PG- gastric carcinoma.
      CONCLUSIONS: Antiparietal cell antibody seropositivity is involved in the
      progression of a subgroup of atrophic gastritis, but not associated with gastric
      carcinogenesis. Severe atrophic gastritis is associated with susceptibility to
      gastric carcinoma, especially the intestinal subtype, and p53 mutations.

PMID- 16638097
TI  - SonoCT improves on conventional ultrasound in the visualization of the pancreatic
      and bile duct: A pilot study.
AB  - BACKGROUND AND AIMS: In sonographic diagnostic investigation, evaluation of the
      ductus Wirsungianus and the ductus hepatocholedochus plays an important role. The
      present prospective study sought to establish whether SonoCT can improve on
      conventional B-mode sonography in the visualization of the pancreatic and bile
      duct. SUBJECTS AND METHODS: In the pilot study, ductus Wirsungianus and ductus
      hepatocholedochus of 14 healthy volunteers were assessed by an experienced and an
      inexperienced examiner, respectively, using both traditional B-mode sonography
      and SonoCT. Assessment was based on a predetermined set of criteria. RESULTS:
      Both examiners were able to determine duct structures significantly more
      effectively using SonoCT. Compared with traditional B-mode sonography, the use of
      SonoCT also led to significant improvements in terms of delineation and clarity
      of representation in both ductus Wirsungianus and ductus hepatocholedochus.
      CONCLUSION: SonoCT yields better results than conventional B-mode sonography in
      terms of delineation, visualization of borders and artefact-free representation
      of both ductus Wirsungianus and ductus hepatocholedochus. Appropriate training
      and experience of the examiner, however, remain key prerequisites for success in
      evaluating pathological changes of the ducts. Future studies will be needed to
      determine whether certain diseases can be diagnosed more readily using SonoCT
      rather than conventional sonographic technique.

PMID- 16638098
TI  - Abnormal gastroesophageal flap valve is highly associated with gastroesophageal
      reflux disease among subjects undergoing routine endoscopy in Taiwan.
AB  - OBJECTIVE: Gastroesophageal flap valve (GEFV) grade predicts severe
      gastroesophageal reflux disease in Caucasians, but its role in other populations
      is unclear. This study evaluated the significance of endoscopic grading of the
      GEFV in Taiwanese subjects. METHODS: Five hundred and six consecutive patients
      undergoing routine check-ups at the National Taiwan University Hospital were
      enrolled. Symptoms of upper gastrointestinal disease and endoscopic severity of
      esophageal mucosal injury were correlated to GEFV grades according to the Hill
      classification. RESULTS: The frequency of abnormal valves (Hill grades III or IV)
      was 27.3%. Of these, 42.7% had erosive esophagitis (EE). The majority of patients
      with EE were classified as Los Angeles grades A and B (79.7 and 16.9%,
      respectively). The prevalence of EE, hiatal hernia and, to a lesser degree, non
      erosive reflux disease, increased with altered GEFV. Patients with abnormal
      valves were younger and more likely to be male, overweight, and to have atypical
      and extraesophageal symptoms. CONCLUSIONS: Taiwanese patients with abnormal GEFVs
      share similar characteristics and risk factors with the patients who have EE.
      Endoscopic grading of the GEFV is highly associated with GERD, and in particular
      EE, in subjects undergoing routine endoscopy.

PMID- 16638099
TI  - Poor correlation between clinical impression, the small colonic polyp and their
      neoplastic risk.
AB  - BACKGROUND AND OBJECTIVES: Significance of the small colonic polyp is unclear and
      its removal is frequently determined by the proceduralist's clinical impression.
      Our aims were to determine if clinical discernment is accurate, and the
      likelihood that lesions < 10 mm are histologically advanced. METHOD: We
      prospectively collected 1988 lesions from 854 subjects (2215 consecutive
      colonoscopies). Lesion size, location, patient age, sex and the colonoscopist's
      clinical impression was recorded. RESULTS: Clinical assessment for neoplasia had
      a sensitivity of 87.4%, specificity of 65.0%, positive predictive value of 76.0%
      and negative predictive value of 80.2%, resulting in an accuracy of 73.4%.
      Factors predictive of correct clinical impression were polyp size, location in
      the rectum and being pedunculated, but not the patient's age, sex or the
      endoscopist's experience. Of the 1434 lesions < or = 5 mm in size, 44.5% were
      neoplastic and 3.5% were histologically advanced. Of the 266 lesions 6-9 mm,
      79.3% were neoplastic, 19.9% were histologically advanced, five demonstrated high
      grade dysplasia and three were malignant. Only two patients with an
      adenocarcinoma or high-grade dysplasia in a polyp <10 mm had a lesion > or =10 mm
      elsewhere in the colon. Of the 288 lesions > or =10 mm in size, 92.7% were
      neoplastic, 29.5% had a villous component, 6.9% demonstrated high-grade dysplasia
      and 29.2% were malignant. Factors predictive of neoplasia were patient age, polyp
      size and sessile nature of the lesion. CONCLUSION: Polyps < 10 mm had a
      significant risk of neoplasia and advanced histology and, in general, clinical
      impression correlated poorly with neoplasia. Removal of all lesions proximal to
      the rectum, regardless of size, should therefore be considered.

PMID- 16638100
TI  - Characteristics of Australian after-hours emergency endoscopy services.
AB  - BACKGROUND AND AIM: Early endoscopic intervention reduces morbidity and mortality
      for patients with high-risk gastrointestinal hemorrhage and gallstones causing
      pancreatitis or ascending cholangitis. For low-risk bleeds 'after-hours'
      endoscopy services allow risk stratification and early, safe discharge leading to
      reduced length of stay. Recognized standards for these services include
      availability of endoscopically trained medical and nursing staff, access to a
      specialized endoscopy unit and full availability of the service. The aim of the
      present study was to assess 'after-hours' endoscopy services at Australian
      teaching hospitals using the British Society of Gastroenterology (BSG) criteria.
      METHODS: A standardized questionnaire based on the BSG guidelines was developed.
      The Gastroenterology Society of Australia provided a list of accredited sites for
      gastroenterology training. An advanced gastroenterology trainee at each hospital
      was interviewed by telephone. RESULTS: Thirty-four centers (100%) provided
      complete data. Gastroscopy, colonoscopy and endoscopic retrograde
      cholangiopancreatography were provided in 100, 58 and 84% of centers,
      respectively. The operation suite followed by endoscopy unit was the most
      frequently used site. However, one-third of centers performed procedures at the
      bedside, including the emergency department or ward. Support staff were not
      consistently trained endoscopically and, in 15 centers (44%), the advanced
      trainees participated in the 'on call' roster with a consultant present for the
      procedure, although this was not consistently the case. CONCLUSIONS: Most
      Australian hospitals offer comprehensive emergency endoscopy services. However,
      few centers fulfill all BSG recommendations. The registrar training and patient
      safety implications of emergency endoscopic services need to be considered in the
      light of these findings.

PMID- 16638101
TI  - Asian contribution to living donor liver transplantation.
AB  - Although the shortage of brain-dead donor organs is a worldwide problem, the
      situation is especially serious in Asia because of various cultural and social
      reasons, and cadaveric organ donation remains below 5 per million population per
      year. Living donor liver transplantation (LDLT) could provide an alternative for
      liver graft for patients with acute and chronic end-stage liver disease. This
      article introduces the important contributions to the development of LDLT by the
      leading Asian liver transplantation centers. The first successful adult LDLT
      using a left-lobe graft was reported by Makuuchi et al. from Japan in 1994. To
      overcome the barrier of graft-size matching for adult patients with use of a left
      lobe graft, a trial of adult LDLT using a right-lobe graft with middle hepatic
      vein was reported with satisfactory outcome by Fan et al. from Hong Kong in 1997.
      Despite the impressive results of right-lobe LDLT, considerable debate persists
      concerning donor safety. Lee et al. from Korea initiated modified right-lobe
      liver grafting with interposition vein grafts to drain anterior segment and two
      left-lobe liver grafting to overcome graft-size insufficiency and to ensure donor
      safety in 1999 and 2000, respectively. In addition to technical innovations,
      indications for liver transplantation have been developed by Asian centers as
      LDLT activity has increased.

PMID- 16638102
TI  - Efficacy and tolerability of pegylated-interferon alpha-2a in hemodialysis
      patients with chronic hepatitis C.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV) is prevalent in hemodialysis (HD)
      patients. These patients experience more side-effects with antiviral treatment.
      The aim of the present study was to evaluate the efficacy and tolerability of
      pegylated interferon (PEG-IFN) alpha-2a in chronic hemodialysis patients with
      chronic hepatitis C. METHODS: Twenty-five patients were included into the study.
      All of the patients were interferon naive, anti-HCV antibodies positive and
      polymerase chain reaction HCV-RNA positive. Twelve of the patients received PEG
      IFN alpha-2a at a dose of 135 microg weekly for 48 weeks (Group 1). The remaining
      13 patients who received no specific treatment were used as controls (Group 2).
      The patients were prospectively followed up for a period of 18 months.
      Biochemical and virological responses were evaluated at the end of the study
      period (end-of-treatment response) and 6 months after the completion of therapy
      (sustained response). RESULTS: Virological end-of-treatment response was observed
      in 10 patients (83.4%) in Group 1 and one patient (7.7%) in Group 2 (P < 0.001).
      Sustained virological response was observed in nine patients (75%) in Group 1 and
      one patient (7.7%) in Group 2 (P < 0.001). Alanine aminotransferase (ALT) levels
      were initially increased in seven patients in Group 1 and normalized in five of
      these patients at the end of the treatment and sustained biochemical response was
      71.4%. In contrast, ALT levels in Group 2 were initially high in five patients
      and normalized in two of them (40%) at the end of the 48 weeks. Even if most of
      the patients experienced several side-effects (anemia 75%, fatigue 58.3%,
      thrombocytopenia 33.3% and leukopenia 33.3%), they did not impose the
      discontinuation of the treatment. CONCLUSION: The present study showed that PEG
      IFN alpha-2a for 48 weeks is efficacious and well tolerated in hemodialysis
      patients with HCV.

PMID- 16638103
TI  - Spontaneous bacterial peritonitis in cirrhotic patients: Is prophylactic
      propranolol therapy beneficial?
AB  - BACKGROUND AND AIM: It has been suggested that propranolol may have a protective
      effect on the development of spontaneous bacterial peritonitis by increasing the
      motility of the bowel and lowering the pressure of the portal vein. The aim of
      this study is to evaluate the association between the use of propranolol and
      development of spontaneous bacterial peritonitis in patients with cirrhosis and
      ascites. METHODS: We retrospectively evaluated 134 patients with cirrhosis and
      ascites admitted consecutively for a period of 2 years. Diagnosis of spontaneous
      bacterial peritonitis was based on an ascitic fluid neutrophilic count of
      >250/mm3 and/or a positive culture without evidence of secondary peritonitis.
      RESULTS: Spontaneous bacterial peritonitis was diagnosed in 39 of 134 (29%)
      patients and 12 of 39 (31%) patients died in hospital compared to only 4% (four
      of 95) of those without spontaneous bacterial peritonitis (P < 0.001). At
      admission, patients with spontaneous bacterial peritonitis, as compared to those
      without, had significantly more encephalopathy (28 vs 11%, P = 0.02) or fever (18
      vs 4%, P = 0.01) and less frequently tense ascites (33 vs 57%, P = 0.02).
      Spontaneous bacterial peritonitis was diagnosed in six of 33 (18%) patients who
      did and in 33 of 101 (33%) who did not receive propranolol therapy (OR = 0.46,
      95% CI: 0.17-1.22, P = 0.17). CONCLUSION: Our data indicate that spontaneous
      bacterial peritonitis significantly increases mortality in patients with
      cirrhosis. Propranolol therapy was not found to be associated with a
      significantly lower risk for spontaneous bacterial peritonitis, but a Type II
      statistical error cannot be definitely excluded. The potential protective effect
      of propranolol on the incidence of spontaneous bacterial peritonitis might
      deserve evaluation in properly designed prospective studies.

PMID- 16638104
TI  - Clinical features and prognosis of hepatocellular carcinoma in young patients
      from a hepatitis B-endemic area.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common
      cancers worldwide. However, the clinical features of young HCC patients have not
      been fully studied. In the present study, we investigated the prevalence,
      clinical characteristics and prognosis of young HCC patients. METHODS: A
      retrospective analysis was performed for HCC patients in our center using Korean
      cancer registry data. Among 4234 patients enrolled, there were 38 patients
      younger than 30 years of age (0.9%). We compared clinical characteristics and
      survival data of these patients (group I) with those of sex-matched, randomly
      selected HCC patients aged 30-59 years (group II; n = 231) and 60 years or older
      (group III; n = 147). RESULTS: Group I showed distinct features compared with
      groups II and III as follows: low frequency of smoking history, high positive
      rate of hepatitis B s antigen, no association with anti-hepatitis C virus
      antibody, high frequency of alpha-fetoprotein > or = 400 ng/mL, well-preserved
      liver function, larger tumor size, more advanced tumor-node-metastasis (TNM)
      stage and Cancer of the Liver Italian Program (CLIP) score and more frequent
      application of surgical resection and chemotherapy as initial treatment. The
      overall survival of group I was worse than that of group II, but similar to that
      of group III. Multivariate analysis showed that TNM stage and CLIP score, not age
      itself, were independent predictive factors for survival. CONCLUSIONS: The
      results suggest that young HCC patients tend to have a poor prognosis owing to
      advanced tumor stage, despite well-preserved liver function and aggressive
      treatment. Further studies regarding the role of HCC screening in young people
      may be useful, especially in hepatitis B virus carriers from high endemic areas.

PMID- 16638105
TI  - Population-based study of the relationship between mutations in the
      hemochromatosis (HFE) gene and arthritis.
AB  - BACKGROUND AND AIM: Mutations in the hemochromatosis (HFE) gene are carried by
      one in three individuals of British Isles descent and may result in increased
      iron stores. These increased iron stores could potentially induce or exacerbate
      diseases, such as arthritis, in which iron has a role in pathogenesis. Although
      arthritis is a well-known association of clinically overt hereditary
      hemochromatosis, controversy surrounds the role of mutations in the HFE gene as
      risk factors for arthritis. The aim of the present study was to determine whether
      mutations in the HFE gene are associated with an increased prevalence of
      arthritis. METHODS: A population-based study was conducted in Busselton, Western
      Australia, of the prevalence of arthritis in 1372 individuals of British Isles
      descent. Participants completed a questionnaire and general physical examination.
      Analysis for C282Y and H63D HFE mutations was undertaken. Unadjusted and adjusted
      odds ratios (OR) were calculated for the relationship between HFE mutations and
      the prevalence of self-reported, doctor-diagnosed arthritis. RESULTS: There was
      no association between the presence of HFE mutations and the prevalence of self
      reported, doctor-diagnosed arthritis (C282Y/wild type (WT) adjusted OR = 1.041
      (95% confidence interval (CI) 0.68-1.61), H63D/WT OR = 0.76 (95% CI 0.53-1.08),
      C282Y/C282Y OR = 0.39 (95% CI 0.04-3.63), C282Y/H 63D OR = 0.808 (95% CI 0.27
      2.42), H63D/H63D OR = 0.419 (95% CI 0.13-1.36)). Overall adjusted OR for
      arthritis in participants with one or more HFE mutations was 0.81 (95% CI 0.61
      1.09). CONCLUSIONS: Mutations of the HFE gene are not risk factors for arthritis
      in populations of British Isles descent.

PMID- 16638106
TI  - Serum and liver iron concentration in dogs with experimentally induced
      hepatopathy.
AB  - BACKGROUND AND AIM: Iron (Fe) status is altered in human and experimental animal
      hepatopathies. In dogs limited data are available. The aim of this study was to
      investigate serum iron (SI), total iron binding capacity (TIBC), percentage
      transferrin saturation (SAT) and Fe status in the liver of dogs with
      experimentally induced hepatopathy. METHODS: Fourteen 1-year-old dogs were
      divided into two equal groups. In order for hepatopathy to be induced, 0.25 mL/kg
      body weight of carbon tetrachloride (CCl4) solution was administered once daily,
      orally, for a 10-week period in group B dogs, while group A dogs were used as
      controls. SI, TIBC and SAT values were measured 3 times before the beginning
      (baseline value) and 10 times at weekly intervals during the experiment. Liver
      samples, obtained before the administration of CCl4 and at the end of the
      experimental period (10 weeks), were subjected to Fe determination, as well as to
      histopathological and histochemical analysis. RESULTS: At the end of the
      experiment SI, TIBC and liver iron concentration, as well as liver total iron
      score were significantly increased in group B dogs. Distribution of granular
      hemosiderin iron in hepatocytes, Kupffer cells, and portal triads was noticed.
      Positive correlations were found between SI and liver Fe concentration, as well
      as histochemically determined Fe. Moreover, positive correlations were evident
      between liver fibrosis and serum, as well as liver Fe values. CONCLUSIONS:
      Experimentally induced chronic hepatopathy in dogs causes Fe status disturbances.
      Increased serum and liver iron concentration produces liver histopathological
      deterioration and it may be worth attention during laboratory evaluation in
      canine hepatopathy.

PMID- 16638107
TI  - Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers:
      Correlation with viral characteristics.
AB  - BACKGROUND: The purpose of the present paper was to correlate hepatitis B virus
      (HBV) genotype, e antigen titer, HBV-DNA level and precore/basal core promoter
      mutations with post-partum e antigen clearance in hepatitis B e antigen (HBeAg)
      positive carrier mothers. METHODS: A total of 40 consecutive HBeAg-positive
      carrier mothers were studied from January 2002 to January 2003. The blood samples
      were taken at delivery, 3-4 months and at 1 year after delivery, and the follow
      up period was until 1 year after delivery. All sera were assayed for HBeAg, HBV
      DNA level, HBV genotype and precore/basal core promoter mutations. The
      correlation between HBV characteristics and post-partum e antigen clearance was
      analyzed by Mann-Whitney, Pearson chi2 and multiple logistic regression tests.
      RESULTS: The mean age of the 40 HBeAg-positive carrier mothers was 29.9 +/- 5.3
      years with a mean parity of 1.4 +/- 0.7. Five of them (group I) had post-partum e
      antigen clearance, which persisted thereafter, whereas the remaining 35 carrier
      mothers (group II) had persistent positivity of HBeAg during the follow-up
      period. The prepartum comparisons of HBV characteristics between groups I and II
      were comparable in terms of demographics and distributions of HBV genotype and
      precore/basal core promoter mutations. In contrast, group I carrier mothers had
      lower HBeAg titer and HBV-DNA level than group II carrier mothers (1:80 vs
      1:4000, P = 0.02, and 3.75 x 10(5) vs 3 x 10(8) copies/mL, P = 0.028,
      respectively). CONCLUSIONS: Post-partum e antigen clearance in HBeAg-positive
      carrier mothers is closely associated with prepartum low HBeAg titer or HBV-DNA
      level.

PMID- 16638108
TI  - Relationship between levels of DNA damage in lymphocytes and histopathological
      severity of chronic hepatitis C and various clinical forms of hepatitis B.
AB  - BACKGROUND AND AIM: A significant proportion of cancer is attributable to DNA
      damage caused by chronic infection and inflammation. Because both hepatitis B and
      C viruses (HBV and HCV, respectively) cause chronic infection and inflammatory
      disease, the aim of the present study was to investigate whether there is a
      difference in peripheral DNA damage in patients with chronic HCV compared with
      patients with chronic HBV; and whether there is an association in the level of
      peripheral DNA damage with a natural history of HBV infection. METHODS: Twenty
      patients with chronic hepatitis C, 20 patients with chronic hepatitis B, 11
      patients with cirrhosis secondary to hepatitis B, 12 inactive hepatitis B s
      antigen (HBsAg) carriers and 21 healthy subjects were included in the study. The
      DNA damage in lymphocytes was determined using the alkaline comet assay. RESULTS:
      Although the chronic hepatitis C group had similar levels of DNA damage compared
      with patients with cirrhosis due to hepatitis B (P > 0.05) and non-cirrhotic
      patients with chronic hepatitis B (P > 0.05), they had higher levels of DNA
      damage compared with inactive HBsAg carriers (P = 0.021) and controls (P =
      0.001). Hepatitis B cirrhotic patients and patients with chronic hepatitis B had
      significantly higher levels of DNA damage than inactive HBsAg carriers (P = 0.002
      and P = 0.012, respectively) and controls (both P = 0.001). Linear logistic
      regression analysis showed that chronic hepatitis C and HBV-related cirrhosis
      were discriminators in determining DNA damage in lymphocytes (beta 0.424 and P =
      0.013, beta 0.393 and P = 0.016, respectively). CONCLUSIONS: Chronic hepatitis C,
      based on the severity of liver disease, or cirrhosis as an advanced form of HBV
      infection increase DNA damage in lymphocytes independently of confounding factors
      such as age, gender, body mass index and smoking habits.

PMID- 16638109
TI  - Gastrointestinal: Adenomatous polyp of the appendix.

PMID- 16638110
TI  - Hepatobiliary and pancreatic: Cystic lymphangioma of the pancreas.

PMID- 16638111
TI  - Hepatobiliary and pancreatic: Hepatic adenoma, focal nodular hyperplasia and
      congenital absence of the portal vein.

PMID- 16638112
TI  - Gastrointestinal: Zosteriform metastases to the skin.

PMID- 16638113
TI  - Gastrointestinal: Fistulae in Crohn's disease.

PMID- 16638114
TI  - Late onset autoimmune thrombocytopenia associated with pegylated interferon-alpha
      2b plus ribavirin treatment for chronic hepatitis C.
AB  - Interferon-induced, immune-mediated, thrombocytopenia is a rare event. In this
      report the case is described of development of severe, reversible, autoimmune
      thrombocytopenia in a patient with chronic hepatitis C virus infection, 6 months
      after the discontinuation of pegylated interferon-alpha-2b plus ribavirin
      treatment. Physicians must be aware that autoimmune thrombocytopenia can occur
      even after the end of treatment, as a late onset complication, especially when
      using the pegylated forms of interferons, which have longer half-lives and
      prolonged activity.

PMID- 16638115
TI  - Gallstone ileus with cholecystoduodenal fistula presenting massive upper
      gastrointestinal hemorrhage.

PMID- 16638116
TI  - Plasma resistin concentration, and steatosis and insulin sensitivity in hepatitis
      C virus-infected patients.

PMID- 16638117
TI  - Hepatitis A protein VP1-2A reduced cell viability in Huh-7 cells with hepatitis C
      virus subgenomic RNA replication.

PMID- 16638118
TI  - Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene
      delivery to the postnatal rat brain by a modular protein vector.
AB  - BACKGROUND: Superoxide mediated oxidative stress is a key neuropathologic
      mechanism in acute central nervous system injuries. We have analyzed the
      neuroprotective efficacy of the transient overexpression of antioxidant enzyme
      Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat
      brain by using a recently constructed modular protein vector for non-viral gene
      delivery termed NLSCt. For this purpose, animals were injected with the NLSCt
      vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after
      intracortical N-methyl-D-aspartate (NMDA) administration, and daily functional
      evaluation was performed. Moreover, 3 days after, lesion volume, neuronal
      degeneration and nitrotyrosine immunoreactivity were evaluated. RESULTS:
      Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved
      functional outcome and a reduced lesion volume at 3 days post lesion. In
      secondary degenerative areas, increased neuronal survival as well as decreased
      numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen.
      Interestingly, injection of the NLSCt vector carrying the control GFP transgene
      also displayed a significant neuroprotective effect but less pronounced.
      CONCLUSION: When the appropriate levels of Cu/Zn SOD are expressed transiently
      after injury using the non-viral modular protein vector NLSCt a neuroprotective
      effect is seen. Thus recombinant modular protein vectors may be suitable for in
      vivo gene therapy, and Cu/Zn SOD should be considered as an interesting
      therapeutic transgene.

PMID- 16638119
TI  - Evaluating indices of traditional ecological knowledge: a methodological
      contribution.
AB  - BACKGROUND: New quantitative methods to collect and analyze data have produced
      novel findings in ethnobiology. A common application of quantitative methods in
      ethnobiology is to assess the traditional ecological knowledge of individuals.
      Few studies have addressed reliability of indices of traditional ecological
      knowledge constructed with different quantitative methods. METHODS: We assessed
      the associations among eight indices of traditional ecological knowledge from
      data collected from 650 native Amazonians. We computed Spearman correlations,
      Chronbach's alpha, and principal components factor analysis for the eight
      indices. RESULTS: We found that indices derived from different raw data were
      weakly correlated (rho<0.5), whereas indices derived from the same raw data were
      highly correlated (rho>0.5; p < 0.001). We also found a relatively high internal
      consistency across data from the eight indices (Chronbach's alpha = 0.78). Last,
      results from a principal components factor analysis of the eight indices suggest
      that the eight indices were positively related, although the association was low
      when considering only the first factor. CONCLUSION: A possible explanation for
      the relatively low correlation between indices derived from different raw data,
      but relatively high internal consistency of the eight indices is that the methods
      capture different aspects of an individual's traditional ecological knowledge. To
      develop a reliable measure of traditional ecological knowledge, researchers
      should collect raw data using a variety of methods and then generate an
      aggregated measure that contains data from the various components of traditional
      ecological knowledge. Failure to do this will hinder cross-cultural comparisons.

PMID- 16638120
TI  - Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human
      protein N-alpha-acetyltransferase.
AB  - BACKGROUND: Protein acetylation is increasingly recognized as an important
      mechanism regulating a variety of cellular functions. Several human protein
      acetyltransferases have been characterized, most of them catalyzing epsilon
      acetylation of histones and transcription factors. We recently described the
      human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts
      with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N
      terminal alpha-acetylation activity. RESULTS: We here describe a human protein,
      hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely
      originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA
      and protein are expressed in several human cell lines. Immunoprecipitation
      experiments show that hARD2 protein potentially interacts with NATH, suggesting
      that hARD2-NATH complexes may be responsible for protein N-alpha-acetylation in
      human cells. In NB4 cells undergoing retinoic acid mediated differentiation, the
      level of endogenous hARD1 and NATH protein decreases while the level of hARD2
      protein is stable. CONCLUSION: A human protein N-alpha-acetyltransferase is
      herein described. ARD2 potentially complements the functions of ARD1, adding more
      flexibility and complexity to protein N-alpha-acetylation in human cells as
      compared to lower organisms which only have one ARD.

PMID- 16638121
TI  - Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral
      Sclerosis.
AB  - BACKGROUND: Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS)
      has been described in neuropathological studies. The presence of cortical atrophy
      in conventional and scientific neuroimaging has been a matter of debate. In
      studies using computertomography, positron emission tomography, proton magnetic
      resonance spectroscopy and conventional T2-weighted and proton-weighted images,
      results have been variable. Recent morphometric studies by magnetic resonance
      imaging have produced conflicting results regarding the extent of grey and white
      matter involvement in ALS patients. METHODS: The authors used optimized voxel
      based morphometry as an unbiased whole brain approach to detect differences
      between regional grey and white matter volumes. Seventeen patients with a
      diagnosis of ALS according to El-Escorial criteria and seventeen age-matched
      controls received a high resolution anatomical T1 scan. RESULTS: In ALS patients
      regional grey matter volume (GMV) reductions were found in the pre- and
      postcentral gyrus bilaterally which extended to premotor, parietal and frontal
      regions bilaterally compared with controls (p < 0.05, corrected for the entire
      volume). The revised ALS functional rating scale showed a positive correlation
      with GMV reduction of the right medial frontal gyrus corresponding to the
      dorsolateral prefrontal cortex. No significant differences were found for white
      matter volumes or when grey and white matter density images were investigated.
      There were no further correlations with clinical variables found. CONCLUSION: In
      ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent
      feature of the disease. Supporting the concept of ALS being a multisystem
      disorder, our study provides further evidence for extramotor involvement which is
      widespread. The lack of correlation with common clinical variables probably
      reflects the fact that heterogeneous disease processes underlie ALS. The
      discrepancy within all published morphometric studies in ALS so far may be
      related to differences in patient cohorts and several methodological factors of
      the data analysis process. Longitudinal studies are required to further clarify
      the time course and distribution of grey and white matter pathology during the
      course of ALS.

PMID- 16638122
TI  - Predicting inpatient violence using an extended version of the Broset-Violence
      Checklist: instrument development and clinical application.
AB  - BACKGROUND: Patient aggression is a common problem in acute psychiatric wards and
      calls for preventive measures. The timely use of preventive measures presupposes
      a preceded risk assessment. The Norwegian Broset-Violence-Checklist (BVC) is one
      of the few instruments suited for short-time prediction of violence of
      psychiatric inpatients in routine care. Aims of our study were to improve the
      accuracy of the short-term prediction of violence in acute inpatient settings by
      combining the Broset-Violence-Checklist (BVC) with an overall subjective clinical
      risk-assessment and to test the application of the combined measure in daily
      practice. METHOD: We conducted a prospective cohort study with two samples of
      newly admitted psychiatric patients for instrument development (219 patients) and
      clinical application (300 patients). Risk of physical attacks was assessed by
      combining the 6-item BVC and a 6-point score derived from a Visual Analog Scale.
      Incidents were registered with the Staff Observation of Aggression Scale-Revised
      SOAS-R. Test accuracy was described as the area under the receiver operating
      characteristic curve (AUCROC). RESULTS: The AUCROC of the new VAS-complemented
      BVC-version (BVC-VAS) was 0.95 in and 0.89 in the derivation and validation study
      respectively. CONCLUSION: The BVC-VAS is an easy to use and accurate instrument
      for systematic short-term prediction of violent attacks in acute psychiatric
      wards. The inclusion of the VAS-derived data did not change the accuracy of the
      original BVC.

PMID- 16638123
TI  - Global transcriptional profiling of the toxic dinoflagellate Alexandrium
      fundyense using Massively Parallel Signature Sequencing.
AB  - BACKGROUND: Dinoflagellates are one of the most important classes of marine and
      freshwater algae, notable both for their functional diversity and ecological
      significance. They occur naturally as free-living cells, as endosymbionts of
      marine invertebrates and are well known for their involvement in "red tides".
      Dinoflagellates are also notable for their unusual genome content and structure,
      which suggests that the organization and regulation of dinoflagellate genes may
      be very different from that of most eukaryotes. To investigate the content and
      regulation of the dinoflagellate genome, we performed a global analysis of the
      transcriptome of the toxic dinoflagellate Alexandrium fundyense under nitrate-
      and phosphate-limited conditions using Massively Parallel Signature Sequencing
      (MPSS). RESULTS: Data from the two MPSS libraries showed that the number of
      unique signatures found in A. fundyense cells is similar to that of humans and
      Arabidopsis thaliana, two eukaryotes that have been extensively analyzed using
      this method. The general distribution, abundance and expression patterns of the
      A. fundyense signatures were also quite similar to other eukaryotes, and at least
      10% of the A. fundyense signatures were differentially expressed between the two
      conditions. RACE amplification and sequencing of a subset of signatures showed
      that multiple signatures arose from sequence variants of a single gene. Single
      signatures also mapped to different sequence variants of the same gene.
      CONCLUSION: The MPSS data presented here provide a quantitative view of the
      transcriptome and its regulation in these unusual single-celled eukaryotes. The
      observed signature abundance and distribution in Alexandrium is similar to that
      of other eukaryotes that have been analyzed using MPSS. Results of signature
      mapping via RACE indicate that many signatures result from sequence variants of
      individual genes. These data add to the growing body of evidence for widespread
      gene duplication in dinoflagellates, which would contribute to the
      transcriptional complexity of these organisms. The MPSS data also demonstrate
      that a significant number of dinoflagellate mRNAs are transcriptionally
      regulated, indicating that dinoflagellates commonly employ transcriptional gene
      regulation along with the post-transcriptional regulation that has been well
      documented in these organisms.

PMID- 16638124
TI  - On systems and control approaches to therapeutic gain.
AB  - BACKGROUND: Mathematical models of cancer relevant processes are being developed
      at an increasing rate. Conceptual frameworks are needed to support new treatment
      designs based on such models. METHODS: A modern control perspective is used to
      formulate two therapeutic gain strategies. RESULTS: Two conceptually distinct
      therapeutic gain strategies are provided. The first is direct in that its goal is
      to kill cancer cells more so than normal cells, the second is indirect in that
      its goal is to achieve implicit therapeutic gains by transferring states of
      cancer cells of non-curable cases to a target state defined by the cancer cells
      of curable cases. The direct strategy requires models that connect anti-cancer
      agents to an endpoint that is modulated by the cause of the cancer and that
      correlates with cell death. It is an abstraction of a strategy for treating
      mismatch repair (MMR) deficient cancers with iodinated uridine (IUdR); IU-DNA
      correlates with radiation induced cell killing and MMR modulates the relationship
      between IUdR and IU-DNA because loss of MMR decreases the removal of IU from the
      DNA. The second strategy is indirect. It assumes that non-curable patient
      outcomes will improve if the states of their malignant cells are first
      transferred toward a state that is similar to that of a curable patient. This
      strategy is difficult to employ because it requires a model that relates drugs to
      determinants of differences in patient survival times. It is an abstraction of a
      strategy for treating BCR-ABL pro-B cell childhood leukemia patients using
      curable cases as the guides. CONCLUSION: Cancer therapeutic gain problem
      formulations define the purpose, and thus the scope, of cancer process modeling.
      Their abstractions facilitate considerations of alternative treatment strategies
      and support syntheses of learning experiences across different cancers.

PMID- 16638125
TI  - Differential evolutionary conservation of motif modes in the yeast protein
      interaction network.
AB  - BACKGROUND: The importance of a network motif (a recurring interconnected pattern
      of special topology which is over-represented in a biological network) lies in
      its position in the hierarchy between the protein molecule and the module in a
      protein-protein interaction network. Until now, however, the methods available
      have greatly restricted the scope of research. While they have focused on the
      analysis in the resolution of a motif topology, they have not been able to
      distinguish particular motifs of the same topology in a protein-protein
      interaction network. RESULTS: We have been able to assign the molecular function
      annotations of Gene Ontology to each protein in the protein-protein interactions
      of Saccharomyces cerevisiae. For various motif topologies, we have developed an
      algorithm, enabling us to unveil one million "motif modes", each of which
      features a unique topological combination of molecular functions. To our
      surprise, the conservation ratio, i.e., the extent of the evolutionary
      constraints upon the motif modes of the same motif topology, varies
      significantly, clearly indicative of distinct differences in the evolutionary
      constraints upon motifs of the same motif topology. Equally important, for all
      motif modes, we have found a power-law distribution of the motif counts on each
      motif mode. We postulate that motif modes may very well represent the
      evolutionary-conserved topological units of a protein interaction network.
      CONCLUSION: For the first time, the motifs of a protein interaction network have
      been investigated beyond the scope of motif topology. The motif modes determined
      in this study have not only enabled us to differentiate among different
      evolutionary constraints on motifs of the same topology but have also opened up
      new avenues through which protein interaction networks can be analyzed.

PMID- 16638126
TI  - Study protocol: SPARCLE--a multi-centre European study of the relationship of
      environment to participation and quality of life in children with cerebral palsy.
AB  - BACKGROUND: SPARCLE is a nine-centre European epidemiological research study
      examining the relationship of participation and quality of life to impairment and
      environment (physical, social and attitudinal) in 8-12 year old children with
      cerebral palsy. Concepts are adopted from the International Classification of
      Functioning, Disability and Health which bridges the medical and social models of
      disability. METHODS/DESIGN: A cross sectional study of children with cerebral
      palsy sampled from total population databases in 9 European regions. Children
      were visited by research associates in each country who had been trained
      together. The main instruments used were KIDSCREEN, Life-H, Strength and
      Difficulties Questionnaire, Parenting Stress Index. A measure of environment was
      developed within the study. All instruments were translated according to
      international guidelines. The potential for bias due to non response and missing
      data will be examined. After initial analysis using multivariate regression of
      how the data captured by each instrument relate to impairment and socio-economic
      characteristics, relationships between the latent traits captured by the
      instruments will then be analysed using structural equation modelling.
      DISCUSSION: This study is original in its methods by directly engaging children
      themselves, ensuring those with learning or communication difficulty are not
      excluded, and by studying in quantitative terms the crucial outcomes of
      participation and quality of life. Specification and publication of this protocol
      prior to analysis, which is not common in epidemiology but well established for
      randomised controlled trials and systematic reviews, should avoid the pitfalls of
      data dredging and post hoc analyses.

PMID- 16638127
TI  - Differential expression of selected histone modifier genes in human solid
      cancers.
AB  - BACKGROUND: Post-translational modification of histones resulting in chromatin
      remodelling plays a key role in the regulation of gene expression. Here we report
      characteristic patterns of expression of 12 members of 3 classes of chromatin
      modifier genes in 6 different cancer types: histone acetyltransferases (HATs)-
      EP300, CREBBP, and PCAF; histone deacetylases (HDACs)- HDAC1, HDAC2, HDAC4,
      HDAC5, HDAC7A, and SIRT1; and histone methyltransferases (HMTs)- SUV39H1and
      SUV39H2. Expression of each gene in 225 samples (135 primary tumours, 47 cancer
      cell lines, and 43 normal tissues) was analysedby QRT-PCR, normalized with 8
      housekeeping genes, and given as a ratio by comparison with a universal reference
      RNA. RESULTS: This involved a total of 13,000 PCR assays allowing for rigorous
      analysis by fitting a linear regression model to the data. Mutation analysis of
      HDAC1, HDAC2, SUV39H1, and SUV39H2 revealed only two out of 181 cancer samples
      (both cell lines) with significant coding-sequence alterations. Supervised
      analysis and Independent Component Analysis showed that expression of many of
      these genes was able to discriminate tumour samples from their normal
      counterparts. Clustering based on the normalized expression ratios of the 12
      genes also showed that most samples were grouped according to tissue type. Using
      a linear discriminant classifier and internal cross-validation revealed that with
      as few as 5 of the 12 genes, SIRT1, CREBBP, HDAC7A, HDAC5 and PCAF, most samples
      were correctly assigned. CONCLUSION: The expression patterns of HATs, HDACs, and
      HMTs suggest these genes are important in neoplastic transformation and have
      characteristic patterns of expression depending on tissue of origin, with
      implications for potential clinical application.

PMID- 16638128
TI  - Co-receptor and co-stimulation blockade for mixed chimerism and tolerance without
      myelosuppressive conditioning.
AB  - BACKGROUND: A major challenge in the application of marrow transplantation as a
      route to immunological tolerance of a transplanted organ is to achieve
      hematopoietic stem cell (HSC) engraftment with minimal myelosuppressive
      treatments. RESULTS: We here describe a combined antibody protocol which can
      achieve long-term engraftment with clinically relevant doses of MHC-mismatched
      bone marrow, without the need for myelosuppressive drugs. Although not
      universally applicable in all strains, we achieved reliable engraftment in
      permissive strains with a two-stage strategy: involving first, treatment with
      anti-CD8 and anti-CD4 in advance of transplantation; and second, treatment with
      antibodies targeting CD4, CD8 and CD40L (CD154) at the time of marrow
      transplantation. Long-term mixed chimerism through co-receptor and co-stimulation
      blockade facilitated tolerance to donor-type skin grafts, without any evidence of
      donor-antigen driven regulatory T cells. CONCLUSION: We conclude that antibodies
      targeting co-receptor and co-stimulatory molecules synergise to enable mixed
      hematopoietic chimerism and central tolerance, showing that neither cytoreductive
      conditioning nor 'megadoses' of donor bone marrow are required for donor HSC to
      engraft in permissive strains.

PMID- 16638129
TI  - Synchrony of change in depressive symptoms, health status, and quality of life in
      persons with clinical depression.
AB  - BACKGROUND: Little is known about longitudinal associations among measures of
      depression, mental and physical health, and quality of life (QOL). We followed
      982 clinically depressed persons to determine which measures changed and whether
      the change was synchronous with change in depressive symptoms. METHODS: Data were
      from the Longitudinal Investigation of Depression Outcomes (LIDO). Depressive
      symptoms, physical and mental health, and quality of life were measured at
      baseline, 6 weeks, 3 months, and 9 months. Change in the measures was examined
      over time and for persons with different levels of change in depressive symptoms.
      RESULTS: On average, all of the measures improved significantly over time, and
      most were synchronous with change in depressive symptoms. Measures of mental
      health changed the most, and physical health the least. The measures of change in
      QOL were intermediate. The 6-week change in QOL could be explained completely by
      change in depressive symptoms. The instruments varied in sensitivity to changes
      in depressive symptoms. CONCLUSION: In clinically depressed persons, measures of
      physical health, mental health, and quality of life showed consistent
      longitudinal associations with measures of depressive symptoms.

PMID- 16638130
TI  - The global health governance of antimicrobial effectiveness.
AB  - Antimicrobial resistance is a growing threat to public health the world over.
      Global health governance strategies need to address the erosion of antimicrobial
      effectiveness on three levels. Firstly, mechanisms to provide incentives for the
      pharmaceutical industry to develop antimicrobials for diseases threatening the
      developing world need to be sought out. Secondly, responsible use of
      antimicrobials by both clinicians and the animal food growing industry needs to
      be encouraged and managed globally. And lastly, in-country and international
      monitoring of changes in antimicrobial effectiveness needs to be stepped up in
      the context of a global health governance strategy.

PMID- 16638131
TI  - A high density of ancient spliceosomal introns in oxymonad excavates.
AB  - BACKGROUND: Certain eukaryotic genomes, such as those of the amitochondriate
      parasites Giardia and Trichomonas, have very low intron densities, so low that
      canonical spliceosomal introns have only recently been discovered through genome
      sequencing. These organisms were formerly thought to be ancient eukaryotes that
      diverged before introns originated, or at least became common. Now however, they
      are thought to be members of a supergroup known as excavates, whose members
      generally appear to have low densities of canonical introns. Here we have used
      environmental expressed sequence tag (EST) sequencing to identify 17 genes from
      the uncultivable oxymonad Streblomastix strix, to survey intron densities in this
      most poorly studied excavate group. RESULTS: We find that Streblomastix genes
      contain an unexpectedly high intron density of about 1.1 introns per gene.
      Moreover, over 50% of these are at positions shared between a broad spectrum of
      eukaryotes, suggesting they are very ancient introns, potentially present in the
      last common ancestor of eukaryotes. CONCLUSION: The Streblomastix data show that
      the genome of the ancestor of excavates likely contained many introns and the
      subsequent evolution of introns has proceeded very differently in different
      excavate lineages: in Streblomastix there has been much stasis while in
      Trichomonas and Giardia most introns have been lost.

PMID- 16638132
TI  - Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse
      oximetry.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is a rare complication of liver
      diseases of different etiologies and may indicate a poor prognosis. Therefore, a
      simple non-invasive screening method to detect HPS would be highly desirable. In
      this study pulse oximetry was evaluated to identify patients with HPS. METHODS:
      In 316 consecutive patients with liver cirrhosis (n = 245), chronic hepatitis (n
      = 69) or non-cirrhotic portal hypertension (n = 2) arterial oxygen saturation
      (SaO2) was determined using a pulse oximeter. In patients with SaO2 < or = 92% in
      supine position and/or a decrease of > or = 4% after change from supine to
      upright position further diagnostic procedures were performed, including contrast
      enhanced echocardiography and perfusion lung scan. RESULTS: Seventeen patients
      (5.4%) had a pathological SaO2. Four patients (1.3%) had HPS. HPS patients had a
      significant lower mean SaO2 in supine (89.7%, SD 5.4 vs. 96.0%, SD 2.3; p =
      0.003) and upright position (84.3%, SD 5.0 vs. 96.0%, SD 2.4; p = 0.001) and had
      a lower mean PaO2 (56.2 mm Hg, SD 15.2 vs. 71.2 mm Hg, SD 20.2; p = 0.02) as
      compared to patients without HPS. The mean deltaSaO2 (difference between supine
      and upright position) was 5.50 (SD 7) in HPS patients compared to non-HPS
      patients who showed no change (p = 0.001). There was a strong correlation between
      shunt volume and the SaO2 values (R = -0.94). CONCLUSION: Arterial SaO2
      determination in supine and upright position is a useful non-invasive screening
      test for HPS and correlates well with the intrapulmonary shunt volume.

PMID- 16638133
TI  - Mathematical modeling of endovenous laser treatment (ELT).
AB  - BACKGROUND AND OBJECTIVES: Endovenous laser treatment (ELT) has been recently
      proposed as an alternative in the treatment of reflux of the Great Saphenous Vein
      (GSV) and Small Saphenous Vein (SSV). Successful ELT depends on the selection of
      optimal parameters required to achieve an optimal vein damage while avoiding side
      effects. Mathematical modeling of ELT could provide a better understanding of the
      ELT process and could determine the optimal dosage as a function of vein
      diameter. STUDY DESIGN/MATERIALS AND METHODS: The model is based on calculations
      describing the light distribution using the diffusion approximation of the
      transport theory, the temperature rise using the bioheat equation and the laser
      induced injury using the Arrhenius damage model. The geometry to simulate ELT was
      based on a 2D model consisting of a cylindrically symmetric blood vessel
      including a vessel wall and surrounded by an infinite homogenous tissue. The
      mathematical model was implemented using the Macsyma-Pdease2D software (Macsyma
      Inc., Arlington, MA, USA). Damage to the vein wall for CW and single shot energy
      was calculated for 3 and 5 mm vein diameters. In pulsed mode, the pullback
      distance (3, 5 and 7 mm) was considered. For CW mode simulation, the pullback
      speed (1, 2, 3 mm/s) was the variable. The total dose was expressed as joules per
      centimeter in order to perform comparison to results already reported in clinical
      studies. RESULTS: In pulsed mode, for a 3 mm vein diameter, irrespective of the
      pullback distance (2, 5 or 7 mm), a minimum fluence of 15 J/cm is required to
      obtain a permanent damage of the intima. For a 5 mm vein diameter, 50 J/cm (15W
      2s) is required. In continuous mode, for a 3 mm and 5 mm vein diameter,
      respectively 65 J/cm and 100 J/cm are required to obtain a permanent damage of
      the vessel wall. Finally, the use of different wavelengths (810 nm or 980 nm)
      played only a minor influence on these results. DISCUSSION AND CONCLUSION: The
      parameters determined by mathematical modeling are in agreement with those used
      in clinical practice. They confirm that thermal damage of the inner vein wall
      (tunica intima) is required to achieve the tissue alterations necessary in order
      to lead the vein to permanent occlusion. However, in order to obtain a high rate
      of success without adverse events, the knowledge of the vein diameter after
      tumescent anesthesia is recommended in order to use the optimal energy. As
      clearly demonstrated by our calculations, both pulsed and continuous mode
      operations of the laser can be efficient. An interesting observation in our model
      is that less amount of energy is required in pulsed mode than in continuous mode.
      Damaging the vein sequentially along its entire length may lead to permanent
      occlusion. However, the pulsed mode requires a very precise positioning of the
      fiber after each pullback and the duration of the treatment is much longer. For
      these reasons, continuous irradiation seems to be preferred by most clinicians.
      This model should serve as a useful tool to simulate and better understand the
      mechanism of action of the ELT.

PMID- 16638134
TI  - SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes
      during suppression of v-Src-induced oncogenesis.
AB  - BACKGROUND: SSeCKS is a major protein kinase C substrate with kinase scaffolding
      and metastasis-suppressor activity whose expression is severely downregulated in
      Src- and Ras-transformed fibroblast and epithelial cells and in human prostate,
      breast, and gastric cancers. We previously used NIH3T3 cells with tetracycline
      regulated SSeCKS expression plus a temperature-sensitive v-Src allele to show
      that SSeCKS re-expression inhibited parameters of v-Src-induced oncogenic growth
      without attenuating in vivo Src kinase activity. METHODS: We use cDNA microarrays
      and semi-quantitative RT-PCR analysis to identify changes in gene expression
      correlating with i) SSeCKS expression in the absence of v-Src activity, ii)
      activation of v-Src activity alone, and iii) SSeCKS re-expression in the presence
      of active v-Src. RESULTS: SSeCKS re-expression resulted in the attenuation of
      critical Src-induced proliferative and pro-angiogenic gene expression including
      Afp, Hif-1alpha, Cdc20a and Pdgfr-beta, and conversely, SSeCKS induced several
      cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and
      Rbbp7. CONCLUSION: Our data provide further evidence that SSeCKS can suppress Src
      induced oncogenesis by modulating gene expression downstream of Src kinase
      activity.

PMID- 16638135
TI  - The use of standardized patients for mock oral board exams in neurology: a pilot
      study.
AB  - BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the
      American Board of Psychiatry and Neurology exam, are commonly part of resident
      assessment during residency training. Exams using real patients selected from
      clinics or hospitals are not standardized and do not allow comparisons of
      resident performance across the residency program. We sought to create a
      standardized patient mock oral board exam that would allow comparison of
      residents' clinical performance. METHODS: Three cases were created and then used
      for this mock oral boards exercise utilizing trained standardized patients.
      Residents from the University of Cincinnati and Indiana University participated
      in the exam. Residents were scored by attending physician examiners who directly
      observed the encounter with the standardized patient. The standardized patient
      also assessed each resident. A post-test survey was administered to ascertain
      participant's satisfaction with the examination process. RESULTS: Resident scores
      were grouped within one standard deviation of the mean, with the exception of one
      resident who was also subjectively felt to "fail" the exam. In exams with two
      faculty "evaluators", scores were highly correlated. The survey showed
      satisfaction with the examination process in general. CONCLUSION: Standardized
      patients can be used for mock oral boards in the live patient format. Our initial
      experience with this examination process was positive. Further testing is needed
      to determine if this examination format is more reliable and valid than
      traditional methods of assessing resident competency.

PMID- 16638136
TI  - Implications of molecular characters for the phylogeny of the Microbotryaceae
      (Basidiomycota: Urediniomycetes).
AB  - BACKGROUND: Anther smuts of the basidiomycetous genus Microbotryum on
      Caryophyllaceae are important model organisms for many biological disciplines.
      Members of Microbotryum are most commonly found parasitizing the anthers of host
      plants in the family Caryophyllaceae, however they can also be found on the
      anthers of members of the Dipsacaceae, Lamiaceae, Lentibulariaceae, and
      Portulacaceae. Additionally, some members of Microbotryum can be found infecting
      other organs of mainly Polygonaceae hosts. Based on ITS nrDNA sequences of
      members of almost all genera in Microbotryaceae, this study aims to resolve the
      phylogeny of the anther smuts and their relationship to the other members of the
      family of plant parasites. A multiple analysis strategy was used to correct for
      the effects of different equally possible ITS sequence alignments on the
      phylogenetic outcome, which appears to have been neglected in previous studies.
      RESULTS: The genera of Microbotryaceae were not clearly resolved, but alignment
      independent moderate bootstrap support was achieved for a clade containing the
      majority of the Microbotryum species. The anther parasites appeared in two
      different well-supported lineages whose interrelationship remained unresolved.
      Whereas bootstrap support values for some clades were highly vulnerable to
      alignment conditions, other clades were more robustly supported. The differences
      in support between the different alignments were much larger than between the
      phylogenetic optimality criteria applied (maximum parsimony and maximum
      likelihood). CONCLUSION: The study confirmed, based on a larger dataset than
      previous work, that the anther smuts on Caryophyllaceae are monophyletic and that
      there exists a native North American group that diverged from the European clade
      before the radiation of the European species. Also a second group of anther smuts
      was revealed, containing parasites on Dipsacaceae, Lamiaceae, and
      Lentibulariaceae. At least the majority of the parasites of Asteraceae appeared
      as a monophylum, but delimitations of some species in this group should be
      reconsidered. Parasitism on Polygonaceae is likely to be the ancestral state for
      the Microbotryaceae on Eudicot hosts.

PMID- 16638137
TI  - RNAmute: RNA secondary structure mutation analysis tool.
AB  - BACKGROUND: RNAMute is an interactive Java application that calculates the
      secondary structure of all single point mutations, given an RNA sequence, and
      organizes them into categories according to their similarity with respect to the
      wild type predicted structure. The secondary structure predictions are performed
      using the Vienna RNA package. Several alternatives are used for the
      categorization of single point mutations: Vienna's RNAdistance based on dot
      bracket representation, as well as tree edit distance and second eigenvalue of
      the Laplacian matrix based on Shapiro's coarse grain tree graph representation.
      RESULTS: Selecting a category in each one of the processed tables lists all
      single point mutations belonging to that category. Selecting a mutation displays
      a graphical drawing of the single point mutation and the wild type, and includes
      basic information such as associated energies, representations and distances.
      RNAMute can be used successfully with very little previous experience and without
      choosing any parameter value alongside the initial RNA sequence. The package runs
      under LINUX operating system. CONCLUSION: RNAMute is a user friendly tool that
      can be used to predict single point mutations leading to conformational
      rearrangements in the secondary structure of RNAs. In several cases of
      substantial interest, notably in virology, a point mutation may lead to a loss of
      important functionality such as the RNA virus replication and translation
      initiation because of a conformational rearrangement in the secondary structure.

PMID- 16638138
TI  - A survey of nuclear ribosomal internal transcribed spacer substitution rates
      across angiosperms: an approximate molecular clock with life history effects.
AB  - BACKGROUND: A full understanding of the patterns and processes of biological
      diversification requires the dating of evolutionary events, yet the fossil record
      is inadequate for most lineages under study. Alternatively, a molecular clock
      approach, in which DNA or amino acid substitution rates are calibrated with
      fossils or geological/climatic events, can provide indirect estimates of clade
      ages and diversification rates. The utility of this approach depends on the rate
      constancy of molecular evolution at a genetic locus across time and across
      lineages. Although the nuclear ribosomal internal transcribed spacer region
      (nrITS) is increasingly being used to infer clade ages in plants, little is known
      about the sources or magnitude of variation in its substitution rate. Here, we
      systematically review the literature to assess substitution rate variation in
      nrITS among angiosperms, and we evaluate possible correlates of the variation.
      RESULTS: We summarize 28 independently calibrated nrITS substitution rates
      ranging from 0.38 x 10(-9) to 8.34 x 10(-9) substitutions/site/yr. We find that
      herbaceous lineages have substitution rates almost twice as high as woody plants,
      on average. We do not find any among-lineage phylogenetic constraint to the
      rates, or any effect of the type of calibration used. Within life history
      categories, both the magnitude of the rates and the variance among rates tend to
      decrease with calibration age. CONCLUSION: Angiosperm nrITS substitution rates
      vary by approximately an order of magnitude, and some of this variation can be
      attributed to life history categories. We make cautious recommendations for the
      use of nrITS as an approximate plant molecular clock, including an outline of
      more appropriate phylogenetic methodology and caveats against over interpretation
      of results. We also suggest that for lineages with independent calibrations, much
      of the variation in nrITS substitution rates may come from uncertainty in
      calibration date estimates, highlighting the importance of accurate and/or
      multiple calibration dates.

PMID- 16638139
TI  - Mental disorders in a population sample with musculoskeletal disorders.
AB  - BACKGROUND: Studies using clinical and volunteer samples have reported an
      elevated prevalence of mood disorders in association with rheumatoid arthritis
      and osteoarthritis. Clinical studies using anxiety rating scales have reported
      inconsistent results, but studies using diagnostic instruments have reported that
      anxiety disorders may be even more strongly associated with arthritis than is
      depression. One study reported an association between lifetime substance use
      disorders and arthritis. METHODS: Data from iteration 1.2 of the Canadian
      Community Health Survey (CCHS) were used. This was a large-scale national
      Canadian health survey which administered the World Mental Health Composite
      International Diagnostic Interview to a sample of 36,984 subjects randomly
      selected from the national population. In the CCHS 1.2, subjects were asked
      whether they had been diagnosed by a health professional with arthritis or
      rheumatism. RESULTS: Subjects reporting arthritis or rheumatism had an elevated
      prevalence of mood, anxiety and substance use disorders. The strength of
      association resembled that seen in an omnibus category reporting any chronic
      condition, but was weaker than that seen with back pain or fibromyalgia. The
      effect of arthritis or rheumatism interacted with age, such that the odds ratios
      became smaller with increasing age. Mood and anxiety disorders, along with
      arthritis or rheumatism made an independent contribution to disability.
      CONCLUSION: Arthritis is associated with psychiatric morbidity in the general
      population, and this morbidity is seen across a variety of mental disorders. The
      strength of association is consistent with that seen in persons with other self
      reported medical conditions.

PMID- 16638140
TI  - Multimedia Bootcamp: a health sciences library provides basic training to promote
      faculty technology integration.
AB  - BACKGROUND: Recent research has shown a backlash against the enthusiastic
      promotion of technological solutions as replacements for traditional educational
      content delivery. Many institutions, including the University of Virginia, have
      committed staff and resources to supporting state-of-the-art, showpiece
      educational technology projects. However, the Claude Moore Health Sciences
      Library has taken the approach of helping Health Sciences faculty be more
      comfortable using technology in incremental ways for instruction and research
      presentations. In July 2004, to raise awareness of self-service multimedia
      resources for instructional and professional development needs, the Library
      conducted a "Multimedia Bootcamp" for nine Health Sciences faculty and fellows.
      METHODS: Case study. RESULTS: Program stewardship by a single Library faculty
      member contributed to the delivery of an integrated learning experience. The
      amount of time required to attend the sessions and complete homework was the
      maximum fellows had to devote to such pursuits. The benefit of introducing
      technology unfamiliar to most fellows allowed program instructors to start
      everyone at the same baseline while not appearing to pass judgment on the
      technology literacy skills of faculty. The combination of wrapping the program in
      the trappings of a fellowship and selecting fellows who could commit to a
      majority of scheduled sessions yielded strong commitment from participants as
      evidenced by high attendance and a 100% rate of assignment completion. Response
      rates to follow-up evaluation requests, as well as continued use of Media Studio
      resources and Library expertise for projects begun or conceived during Bootcamp,
      bode well for the long-term success of this program. CONCLUSION: An incremental
      approach to integrating technology with current practices in instruction and
      presentation provided a supportive yet energizing environment for Health Sciences
      faculty. Keys to this program were its faculty focus, traditional hands-on
      instruction, unrestricted access to technology tools and support, and inclusion
      of criteria for evaluating when multimedia can augment pedagogical aims.

PMID- 16638141
TI  - A new initiative for the development of new diagnostic tests for human African
      trypanosomiasis.
AB  - Human African trypanosomiasis is a threat to millions of people living in sub
      Saharan countries and is fatal unless treated. At present, the serological and
      parasitological tests used in the field for diagnosis of sleeping sickness have
      low specificity and sensitivity. There is clearly an urgent need for accurate
      tools for both diagnosis and staging of the disease. The Foundation for
      Innovative New Diagnostics and the World Health Organization have announced that
      they will collaborate to develop and evaluate new diagnostic tests for human
      African trypanosomiasis.

PMID- 16638142
TI  - Evaluating the quality of interaction between medical students and nurses in a
      large teaching hospital.
AB  - BACKGROUND: Effective health care depends on multidisciplinary collaboration and
      teamwork, yet little is known about how well medical students and nurses interact
      in the hospital environment, where physicians-in-training acquire their first
      experiences as members of the health care team. The objective of this study was
      to evaluate the quality of interaction between third-year medical students and
      nurses during clinical rotations. METHODS: We surveyed 268 Indiana University
      medical students and 175 nurses who worked at Indiana University Hospital, the
      School's chief clinical training site. The students had just completed their
      third year of training. The survey instrument consisted of 7 items that measured
      "relational coordination" among members of the health care team, and 9 items that
      measured psychological distress. RESULTS: Sixty-eight medical students (25.4%)
      and 99 nurses (56.6%) completed the survey. The relational coordination score
      (ranked 1 to 5, low to high), which provides an overall measure of interaction
      quality, showed that medical students interacted with residents the best (4.16)
      and with nurses the worst (2.98; p < 0.01). Conversely, nurses interacted with
      other nurses the best (4.36) and with medical students the worst (2.68; p <
      0.01). Regarding measures of psychological distress (ranked 0 to 4, low to high),
      the interpersonal sensitivity score of medical students (1.56) was significantly
      greater than that of nurses (1.03; p < 0.01), whereas the hostility score of
      nurses (0.59) was significantly greater than that of medical students (0.39; p <
      0.01). CONCLUSION: The quality of interaction between medical students and nurses
      during third-year clinical rotations is poor, which suggests that medical
      students are not receiving the sorts of educational experiences that promote
      optimal physician-nurse collaboration. Medical students and nurses experience
      different levels of psychological distress, which may adversely impact the
      quality of their interaction.

PMID- 16638143
TI  - Differential effects of antigens from L. braziliensis isolates from disseminated
      and cutaneous leishmaniasis on in vitro cytokine production.
AB  - BACKGROUND: Disseminated leishmaniasis is an emerging infectious disease, mostly
      due to L. braziliensis, which has clinical and histopathological features
      distinct from cutaneous leishmaniasis. METHODS: In the current study we evaluated
      the in vitro production of the cytokines IFN-gamma, TNF-alpha, IL-5 and IL-10 by
      peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and
      24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis
      antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis
      isolates. RESULTS: Regardless of the source of L. braziliensis antigens, PBMC
      from cutaneous leishmaniasis patients produced significantly higher IFN-gamma
      than PBMC from disseminated leishmaniasis patients. Levels of TNF-alpha by PBMC
      from cutaneous leishmaniasis patients were significantly higher than disseminated
      leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis
      antigens. The levels of IL-5 and IL-10 production by PBMC were very low and
      similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis
      patients. The immune response of each patient evaluated by the two L.
      braziliensis antigens was assessed in a paired analysis in which we showed that
      L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent
      than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering
      IFN-gamma and TNF-alpha production in both diseases and IL-5 only in cutaneous
      leishmaniasis patients. CONCLUSION: This study provides evidence that antigens
      prepared from genotypically distinct strains of L. braziliensis induce different
      degrees of immune response. It also indicates that both parasite and host play a
      role in the outcome of L. braziliensis infection.

PMID- 16638144
TI  - Comparison and evaluation of experimental mediastinitis models: precolonized
      foreign body implants and bacterial suspension inoculation seems promising.
AB  - BACKGROUND: Post-sternotomy mediastinitis (PSM) is a devastating surgical
      complication affecting 1-3% of patients that undergo cardiac surgery.
      Staphylococcus aureus is one of the most commonly encountered bacterial pathogen
      cultured from mediastinal samples obtained from patients with PSM. A component of
      the membrane of the gram positive bacteria, lipoteichoic acid, stimulates the
      blood monocytes and macrophages to secrete cytokines, radicals and nitrogen
      species leading to oxido-inflammatory damage. This seems to be responsible for
      the high mortality rate in PSM. For the evaluation of the pathogenesis of
      infection or for the investigation of alternative treatment models in infection,
      no standard model of mediastinitis seems to be available. In this study, we
      evaluated four mediastinitis models in rats. METHODS: The rats were divided into
      four groups to form different infection models. Group A: A suspension of 1 x 107
      colony-forming units Staphylococcus aureus in 0,5 mL was inoculated from the
      right second intercostal space into the mediastinum. Group B: A hole was created
      in the right second intercostal space and a piece of stainless-steel implant with
      a length of 0.5 cm was inserted into the mediastinum and a suspension of 1 x 107
      cfu bacteria in 0,5 mL was administered via the tail vein. Group C: Precolonized
      stainless-steel implant was inserted into the mediastinum. Group D: Precolonized
      stainless-steel implant was inserted into the mediastinum and the bacteria
      suspension was also injected into the mediastinum. On the 10th day, rats were
      sacrificed and the extension of infection in the mediastenae was evaluated by
      quantitative cultures. Myeloperoxidase activity (MPO) and malondialdehyde (MDA)
      levels were determined in the sera to evaluate the neutrophil activation and
      assess the inflammatory oxidation. RESULTS: The degree of infection in group C
      and D were 83.3% and 100% respectively (P < 0.001). MDA levels were significantly
      higher in these two groups than the others (P < 0.001). CONCLUSION: Infected
      implants and high bacterial concentration administration were the two important
      components that played a significant role in the outcome of a successful
      infection in mediastinum in a rat model.

PMID- 16638145
TI  - CGHScan: finding variable regions using high-density microarray comparative
      genomic hybridization data.
AB  - BACKGROUND: Comparative genomic hybridization can rapidly identify chromosomal
      regions that vary between organisms and tissues. This technique has been applied
      to detecting differences between normal and cancerous tissues in eukaryotes as
      well as genomic variability in microbial strains and species. The density of
      oligonucleotide probes available on current microarray platforms is particularly
      well-suited for comparisons of organisms with smaller genomes like bacteria and
      yeast where an entire genome can be assayed on a single microarray with high
      resolution. Available methods for analyzing these experiments typically confine
      analyses to data from pre-defined annotated genome features, such as entire
      genes. Many of these methods are ill suited for datasets with the number of
      measurements typical of high-density microarrays. RESULTS: We present an
      algorithm for analyzing microarray hybridization data to aid identification of
      regions that vary between an unsequenced genome and a sequenced reference genome.
      The program, CGHScan, uses an iterative random walk approach integrating multi
      layered significance testing to detect these regions from comparative genomic
      hybridization data. The algorithm tolerates a high level of noise in measurements
      of individual probe intensities and is relatively insensitive to the choice of
      method for normalizing probe intensity values and identifying probes that differ
      between samples. When applied to comparative genomic hybridization data from a
      published experiment, CGHScan identified eight of nine known deletions in a
      Brucella ovis strain as compared to Brucella melitensis. The same result was
      obtained using two different normalization methods and two different scores to
      classify data for individual probes as representing conserved or variable genomic
      regions. The undetected region is a small (58 base pair) deletion that is below
      the resolution of CGHScan given the array design employed in the study.
      CONCLUSION: CGHScan is an effective tool for analyzing comparative genomic
      hybridization data from high-density microarrays. The algorithm is capable of
      accurately identifying known variable regions and is tolerant of high noise and
      varying methods of data preprocessing. Statistical analysis is used to define
      each variable region providing a robust and reliable method for rapid
      identification of genomic differences independent of annotated gene boundaries.

PMID- 16638146
TI  - Impact of medical students' descriptive evaluations on long-term course
      development.
AB  - BACKGROUND: In medical education, feedback from students is helpful in course
      evaluation. However, the impact of medical students' feedback on long-term course
      development is seldom reported. In this project we studied the correspondence
      between medical students' descriptive evaluations and key features of course
      development over five years. METHODS: Qualitative content analysis was used. The
      context was consultation skills courses in the middle of the Goteborg
      undergraduate curriculum during five years. An analysis of 158 students'
      descriptive evaluations was brought together with an analysis of key features of
      course development; learning objectives, course records, protocols from teachers'
      evaluations and field notes. Credibility of data was tested by two colleagues and
      by presenting themes at seminars and conferences. Authors' experiences of
      evaluating the course over many years were also used. RESULTS: A corresponding
      pattern was found in students' descriptive evaluations and key features of course
      development, indicating the impact of students' open-ended feed-back. Support to
      facilitators and a curriculum reform also contributed. Students' descriptive
      feedback was both initiating and validating longitudinal course implementation.
      During five years, students' descriptive evaluations and teachers' course records
      were crucial sources in a learner-centred knowledge-building process of course
      development. CONCLUSION: Students' descriptive evaluations and course records can
      be seen as important instruments in developing both courses and students'
      learning. Continuity and endurance in the evaluation process must be emphasized
      for achieving relevant and useful results.

PMID- 16638147
TI  - Does population screening for Chlamydia trachomatis raise anxiety among those
      tested? Findings from a population based chlamydia screening study.
AB  - BACKGROUND: The advent of urine testing for Chlamydia trachomatis has raised the
      possibility of large-scale screening for this sexually transmitted infection,
      which is now the most common in the United Kingdom. The purpose of this study was
      to investigate the effect of an invitation to be screened for chlamydia and of
      receiving a negative result on levels of anxiety, depression and self-esteem.
      METHODS: 19,773 men and women aged 16 to 39 years, selected at random from 27
      general practices in two large city areas (Bristol and Birmingham) were invited
      by post to send home-collected urine samples or vulvo-vaginal swabs for chlamydia
      testing. Questionnaires enquiring about anxiety, depression and self-esteem were
      sent to random samples of those offered screening: one month before the dispatch
      of invitations; when participants returned samples; and after receiving a
      negative result. RESULTS: Home screening was associated with an overall reduction
      in anxiety scores. An invitation to participate did not increase anxiety levels.
      Anxiety scores in men were lower after receiving the invitation than at baseline.
      Amongst women anxiety was reduced after receipt of negative test results. Neither
      depression nor self-esteem scores were affected by screening. CONCLUSION: Postal
      screening for chlamydia does not appear to have a negative impact on overall
      psychological well-being and can lead to a decrease in anxiety levels among
      respondents. There is, however, a clear difference between men and women in when
      this reduction occurs.

PMID- 16638148
TI  - Transcriptomes of human prostate cells.
AB  - BACKGROUND: The gene expression profiles of most human tissues have been studied
      by determining the transcriptome of whole tissue homogenates. Due to the solid
      composition of tissues it is difficult to study the transcriptomes of individual
      cell types that compose a tissue. To overcome the problem of heterogeneity we
      have developed a method to isolate individual cell types from whole tissue that
      are a source of RNA suitable for transcriptome profiling. RESULTS: Using
      monoclonal antibodies specific for basal (integrin beta4), luminal secretory
      (dipeptidyl peptidase IV), stromal fibromuscular (integrin alpha 1), and
      endothelial (PECAM-1) cells, respectively, we separated the cell types of the
      prostate with magnetic cell sorting (MACS). Gene expression of MACS-sorted cell
      populations was assessed with Affymetrix GeneChips. Analysis of the data provided
      insight into gene expression patterns at the level of individual cell populations
      in the prostate. CONCLUSION: In this study, we have determined the transcriptome
      profile of a solid tissue at the level of individual cell types. Our data will be
      useful for studying prostate development and cancer progression in the context of
      single cell populations within the organ.

PMID- 16638149
TI  - The complete chloroplast genome sequence of the chlorophycean green alga
      Scenedesmus obliquus reveals a compact gene organization and a biased
      distribution of genes on the two DNA strands.
AB  - BACKGROUND: The phylum Chlorophyta contains the majority of the green algae and
      is divided into four classes. While the basal position of the Prasinophyceae is
      well established, the divergence order of the Ulvophyceae, Trebouxiophyceae and
      Chlorophyceae (UTC) remains uncertain. The five complete chloroplast DNA (cpDNA)
      sequences currently available for representatives of these classes display
      considerable variability in overall structure, gene content, gene density, intron
      content and gene order. Among these genomes, that of the chlorophycean green alga
      Chlamydomonas reinhardtii has retained the least ancestral features. The two
      single-copy regions, which are separated from one another by the large inverted
      repeat (IR), have similar sizes, rather than unequal sizes, and differ radically
      in both gene contents and gene organizations relative to the single-copy regions
      of prasinophyte and ulvophyte cpDNAs. To gain insights into the various changes
      that underwent the chloroplast genome during the evolution of chlorophycean green
      algae, we have sequenced the cpDNA of Scenedesmus obliquus, a member of a
      distinct chlorophycean lineage. RESULTS: The 161,452 bp IR-containing genome of
      Scenedesmus features single-copy regions of similar sizes, encodes 96 genes, i.e.
      only two additional genes (infA and rpl12) relative to its Chlamydomonas
      homologue and contains seven group I and two group II introns. It is clearly more
      compact than the four UTC algal cpDNAs that have been examined so far, displays
      the lowest proportion of short repeats among these algae and shows a stronger
      bias in clustering of genes on the same DNA strand compared to Chlamydomonas
      cpDNA. Like the latter genome, Scenedesmus cpDNA displays only a few ancestral
      gene clusters. The two chlorophycean genomes share 11 gene clusters that are not
      found in previously sequenced trebouxiophyte and ulvophyte cpDNAs as well as a
      few genes that have an unusual structure; however, their single-copy regions
      differ considerably in gene content. CONCLUSION: Our results underscore the
      remarkable plasticity of the chlorophycean chloroplast genome. Owing to this
      plasticity, only a sketchy portrait could be drawn for the chloroplast genome of
      the last common ancestor of Scenedesmus and Chlamydomonas.

PMID- 16638150
TI  - Learning to mark: a qualitative study of the experiences and concerns of medical
      markers.
AB  - BACKGROUND: Although there is published research on the methods markers use in
      marking various types of assessment, there is relatively little information on
      the processes markers use in approaching a marking exercise. This qualitative
      paper describes the preparation and experiences of general practice (GP) teachers
      who undertake marking a written assessment in an undergraduate medical course.
      METHODS: Semi-structured interviews were conducted with seven of the 16 GP tutors
      on an undergraduate course. The purposive sample comprised two new markers, two
      who had marked for a couple of years and three experienced markers. Each
      respondent was interviewed twice, once following a formative assessment of a
      written case study, and again after a summative assessment. All interviews were
      audio-taped and analysed for emerging themes. A respondent validation exercise
      was conducted with all 16 GP tutors. RESULTS: Markers had internal concerns about
      their ability to mark fairly and made considerable efforts to calibrate their
      marking. They needed guidance and coaching when marking for the first time and
      adopted a variety of marking styles, reaching a decision through a number of
      routes. Dealing with pass/fail borderline scripts and the consequences of the
      mark on the student were particular concerns. Even experienced markers felt the
      need to calibrate their marks both internally and externally CONCLUSION: Previous
      experience of marking appears to improve markers' confidence and is a factor in
      determining the role which markers adopt. Confidence can be improved by giving
      clear instructions, along with examples of marking. The authors propose that one
      method of providing this support and coaching could be by a process of peer
      review of a selection of papers prior to the main marking. New markers in
      particular would benefit from further guidance, however they are influenced by
      others early on in their marking career and course organisers should be mindful
      of this when arranging double marking.

PMID- 16638151
TI  - GenePING: secure, scalable management of personal genomic data.
AB  - BACKGROUND: Patient genomic data are rapidly becoming part of clinical decision
      making. Within a few years, full genome expression profiling and genotyping will
      be affordable enough to perform on every individual. The management of such
      sizeable, yet fine-grained, data in compliance with privacy laws and best
      practices presents significant security and scalability challenges. RESULTS: We
      present the design and implementation of GenePING, an extension to the PING
      personal health record system that supports secure storage of large, genome-sized
      datasets, as well as efficient sharing and retrieval of individual datapoints
      (e.g. SNPs, rare mutations, gene expression levels). Even with full access to the
      raw GenePING storage, an attacker cannot discover any stored genomic datapoint on
      any single patient. Given a large-enough number of patient records, an attacker
      cannot discover which data corresponds to which patient, or even the size of a
      given patient's record. The computational overhead of GenePING's security
      features is a small constant, making the system usable, even in emergency care,
      on today's hardware. CONCLUSION: GenePING is the first personal health record
      management system to support the efficient and secure storage and sharing of
      large genomic datasets. GenePING is available online at
      http://ping.chip.org/genepinghtml, licensed under the LGPL.

PMID- 16638152
TI  - A novel scoring schema for peptide identification by searching protein sequence
      databases using tandem mass spectrometry data.
AB  - BACKGROUND: Tandem mass spectrometry (MS/MS) is a powerful tool for protein
      identification. Although great efforts have been made in scoring the correlation
      between tandem mass spectra and an amino acid sequence database, improvements
      could be made in three aspects, including characterization ofpeaks in spectra,
      adoption of effective scoring functions and access to thereliability of matching
      between peptides and spectra. RESULTS: A novel scoring function is presented,
      along with criteria to estimate the performance confidence of the function.
      Through learning the typesof product ions and the probability of generating them,
      a hypothetic spectrum was generated for each candidate peptide. Then relative
      entropy was introduced to measure the similarity between the hypothetic and the
      observed spectra. Based on the extreme value distribution (EVD) theory, a
      threshold was chosen to distinguish a true peptide assignment from a random one.
      Tests on a public MS/MS dataset demonstrated that this method performs better
      than the well-known SEQUEST. CONCLUSION: A reliable identification of proteins
      from the spectra promises a more efficient application of tandem mass
      spectrometry to proteomes with high complexity.

PMID- 16638153
TI  - Invasion of Africa by a single pfcrt allele of South East Asian type.
AB  - BACKGROUND: Because of its dramatic public health impact, Plasmodium falciparum
      resistance to chloroquine (CQ) has been documented early on. Chloroquine
      resistance (CQR) emerged in the late 1950's independently in South East Asia and
      South America and progressively spread over all malaria areas. CQR was reported
      in East Africa in the 1970's, and has since invaded the African continent. Many
      questions remain about the actual selection and spreading process of CQR
      parasites, and about the evolution of the ancestral mutant gene(s) during
      spreading. METHODS: Eleven clinical isolates of P. falciparum from Cambodia and
      238 from Africa (Senegal, Ivory Coast, Bukina Faso, Mali, Guinea, Togo, Benin,
      Niger, Congo, Madagascar, Comoros Islands, Tanzania, Kenya, Mozambique, Cameroun,
      Gabon) were collected during active case detection surveys carried out between
      1996 and 2001. Parasite DNA was extracted from frozen blood aliquots and
      amplification of the gene pfcrt exon 2 (codon 72-76), exon 4 and intron 4 (codon
      220 and microsatellite marker) were performed. All fragments were sequenced.
      RESULTS: 124 isolates with a sensitive (c76/c220:CVMNK/A) haplotype and 125
      isolates with a resistant c76/c220:CVIET/S haplotype were found. The
      microsatellite showed 17 different types in the isolates carrying the
      c76/c220:CVMNK/A haplotype while all 125 isolates with a CVIET/S haplotype but
      two had a single microsatellite type, namely (TAAA)3(TA)15, whatever the location
      or time of collection. CONCLUSION: Those results are consistent with the
      migration of a single ancestral pfcrt CQR allele from Asia to Africa. This is
      related to the importance of PFCRT in the fitness of P. falciparum point out this
      protein as a potential target for developments of new antimalarial drugs.

PMID- 16638154
TI  - The regional differences in prevalence, medical expenditures and risk factors for
      injury in Taiwanese teenagers.
AB  - BACKGROUND: Injury is the leading cause of death in teenagers worldwide. In
      Taiwan, people in mountainous areas have a 4 to 8 years shorter life span than
      the general population. Injury among teenagers is likely a major cause. The
      objective of this study was to investigate the regional differences in the
      prevalence, the risk factors, and the medical expenditures for injury among
      Taiwanese teenagers. METHOD: An equal probability national sample was used. In
      addition, representative samples from mountainous areas and offshore islands were
      used. Only those who aged between 12 and 21 years, and signed the consent form
      permitting us to link their National Health Insurance (NHI) claim data were
      included in the analysis. Injury-related visits and expenditures in outpatient
      services were extracted from the NHI data. Logistic regression was used to
      examine the factors associated with injury. For those who had injury related
      outpatient visits, mixed model was used to examine the factors associated with
      medical expenditures accounting for multiple visits by the same individual.
      RESULTS: The prevalence of nonfatal injury was around 30% of teenagers in Taiwan.
      It was 10% higher in mountainous areas. Factors associated with injury were those
      who lived in mountainous areas (adjusted odds ratio [OR]: 1.7; 95%; confidence
      interval [CI]: 1.3-2.3), males (OR: 1.3; 95%; CI: 1.1-1.6), older teens (18-21
      years old), and those with risk behavior were positively associated with injury.
      These factors were also associated with the number of injury-related outpatient
      visits. However, teenagers in mountainous areas did not spend more on medical
      care than those who lived in metropolitan Taiwan. CONCLUSION: Around 30% of the
      teenagers were injured in a year, not including the dead. Each of the injured
      spent at least 851.4NTD (approximately 27USD) for outpatient visits. The scope of
      the problem was not trivial. Hazardous environments and high-risk behaviors were
      the universal causes. In remote areas, lack of medical resources was another
      possibility. Empowering local people to design prevention programs according to
      their needs is recommended.

PMID- 16638155
TI  - Reconstruction after esophagectomy in patients with [partial] gastric resection.
      Case report and review of the literature of the use of remnant stomach.
AB  - BACKGROUND: Bowel reconstruction after subtotal esophagectomy represents a
      problem when a previous distal gastrectomy was performed: usually the colon or
      jejunum is used. METHODS: In a 10 year period 126 patients with primary
      esophageal cancer underwent esophageal resection in our Department. Surgical
      procedures were 57% two-phase subtotal oesophagectomy, 23% transhiatal, 9%
      stripping, 10 three-phase total esophagectomy and 2 endoscopic resections.
      RESULTS: In 112 patients alimentary tract reconstruction was achieved by means of
      esophago-gastric anastomosis. Reconstruction was performed using colon in 10
      cases and jejunum in 2. We describe the technical aspects of esophagectomy and
      gastric reconstruction in a patient with previous antrectomy and Billroth II
      reconstruction. The procedure was performed via a combined laparotomy and
      thoracotomy with anastomosis at the level of the azygous vein using the remnant
      stomach. CONCLUSION: Few technical reports have been reported in literature about
      the use of remnant stomach in reconstruction for subtotal esophagectomy
      subsequent to distal gastrectomy. Several hypotheses are made to explain the
      maintenance of the gastric vascular integrity as its intramural network without
      micro-vascular anastomosis.

PMID- 16638156
TI  - Spatial analysis of hemorrhagic fever with renal syndrome in China.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is endemic in many
      provinces with high incidence in mainland China, although integrated intervention
      measures including rodent control, environment management and vaccination have
      been implemented for over ten years. In this study, we conducted a geographic
      information system (GIS)-based spatial analysis on distribution of HFRS cases for
      the whole country with an objective to inform priority areas for public health
      planning and resource allocation. METHODS: Annualized average incidence at a
      county level was calculated using HFRS cases reported during 1994-1998 in
      mainland China. GIS-based spatial analyses were conducted to detect spatial
      autocorrelation and clusters of HFRS incidence at the county level throughout the
      country. RESULTS: Spatial distribution of HFRS cases in mainland China from 1994
      to 1998 was mapped at county level in the aspects of crude incidence, excess
      hazard and spatial smoothed incidence. The spatial distribution of HFRS cases was
      nonrandom and clustered with a Moran's I = 0.5044 (p = 0.001). Spatial cluster
      analyses suggested that 26 and 39 areas were at increased risks of HFRS (p <
      0.01) with maximum spatial cluster sizes of < or = 20% and < or = 10% of the
      total population, respectively. CONCLUSION: The application of GIS, together with
      spatial statistical techniques, provide a means to quantify explicit HFRS risks
      and to further identify environmental factors responsible for the increasing
      disease risks. We demonstrate a new perspective of integrating such spatial
      analysis tools into the epidemiologic study and risk assessment of HFRS.

PMID- 16638157
TI  - Accelerated discharge of patients in the event of a major incident: observational
      study of a teaching hospital.
AB  - BACKGROUND: Since October 2002 in the UK Primary Care Trusts (PCTs) have had
      statutory responsibility for having and maintaining a Major Incident plan and
      since 2005 they have been obliged to co-operate with other responders to an
      incident. We aimed to establish the number of beds in our Trust which could be
      freed up over set periods of time in the event of a major incident and the nature
      and quantity of support which might be required from PCTs in order to achieve
      this. METHODS: Repeated survey over 12 days in 3 months of hospital bed occupancy
      by type of condition and discharge capacity in an 855-bed UK tertiary teaching
      hospital also providing secondary care services. Outcome measures were bed spaces
      which could be generated, timescale over which this could happen and level and
      type of PCT support which would be required to achieve this. RESULTS: Mean beds
      available were 78 immediately, a further 69 in 1-4 hours and a further 155 in 4
      12 hours, generating a total of 302 beds (36% of hospital capacity) within 12
      hours of an incident. This would require support from a PCT of 150,000 population
      of 10 nursing care beds, 20 therapy-supported intermediate care beds, and 25 care
      packages in patients' own homes. CONCLUSION: In order to fulfill the requirements
      of the Civil Contingencies Act 2004, PCTs should plan to have surge capacity in
      the order of 30 residential placements and 25 community support packages per
      150,000 population to support Acute Trusts in the event of a major incident.

PMID- 16638158
TI  - Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit
      patients who failed previous weaning attempts following prolonged mechanical
      ventilation: a pilot study.
AB  - INTRODUCTION: Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist
      that exhibits sedative, analgesic, anxiolytic, and sympatholytic effects without
      respiratory-drive depression. We prospectively evaluated the use of
      dexmedetomidine to facilitate the withdrawal of mechanical ventilation and
      extubation in 5 trauma/surgical intensive-care-unit patients who had failed
      previous weaning attempts due to agitation and hyperdynamic cardiopulmonary
      response. METHODS: Intravenous infusion of dexmedetomidine commenced at 0.5 or
      0.7 microg/kg/h without a loading dose. Background sedation and analgesia with
      propofol, benzodiazepines, and opiates was discontinued or reduced as tolerated.
      Dexmedetomidine infusion was titrated between 0.2 and 0.7 microg/kg/h to maintain
      a stable cardiopulmonary response and modified Ramsay Sedation Score between 2
      and 4. RESULTS: Following dexmedetomidine administration, propofol infusion was
      weaned and discontinued in 4 patients. In the fifth patient, benzodiazepine and
      opiate infusions were reduced. Ventilatory support in all patients could be
      weaned to continuous positive airway pressure of 5 cm H2O without agitation,
      hemodynamic instability, or respiratory decompensation. All patients were
      extubated while receiving dexmedetomidine infusion (mean dose of 0.32 +/- 0.08
      microg/kg/h). One patient required reintubation for upper-airway obstruction.
      CONCLUSION: Dexmedetomidine appears to maintain adequate sedation without
      hemodynamic instability or respiratory-drive depression, and thus may facilitate
      extubation in agitated difficult-to-wean patients; it therefore deserves further
      investigation toward this novel use.

PMID- 16638159
TI  - The impact of endotracheal suctioning on gas exchange and hemodynamics during
      lung-protective ventilation in acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the respiratory and hemodynamic effects of open suctioning
      (OS) versus closed suctioning (CS) during pressure-control (PC) and volume
      control (VC) ventilation, using a lung-protective ventilation strategy in an
      animal model of acute respiratory distress syndrome (ARDS). SETTING: Animal
      laboratory in a university hospital. DESIGN: Randomized cross-over evaluation.
      ANIMALS: Eight female Dorset sheep. INTERVENTIONS: Lung lavage was used to
      simulate ARDS. We applied VC and PC mechanical ventilation with a tidal volume of
      6 mL/kg and positive end-expiratory pressure (PEEP), adjusted based on a table of
      PEEP versus fraction of inspired oxygen (FIO2). Suctioning was performed for 10 s
      with a suction pressure of -100 mm Hg, during both OS and CS. OS and CS were
      randomly performed with each animal. Hemodynamics and arterial blood gases were
      recorded before, during, and after endotracheal suctioning. RESULTS: The
      PaO2/FIO2 ratios before suctioning were similar in all groups, as were the PEEP
      and FIO2. PaO2/FIO2 was lower after OS than after CS/VC or CS/PC. There was no
      post-suctioning difference in oxygenation between CS/VC and CS/PC. PaCO2 recorded
      10 min after suctioning was greater than the presuctioning value, in all groups.
      Intrapulmonary shunt fraction increased between baseline and 10 min post
      suctioning with OS and CS/VC, but did not significantly increase with CS/PC.
      There were no significant changes in hemodynamics pre-suctioning versus post
      suctioning with OS, CS/VC, or CS/PC. CONCLUSION: PaO2/FIO2) was better maintained
      during CS with both VC and PC modes during lung-protective ventilation for ARDS,
      as compared with OS, and shunt fraction post-suctioning changed least with PC.

PMID- 16638160
TI  - The importance of nonelectrostatic materials in holding chambers for delivery of
      hydrofluoroalkane albuterol.
AB  - INTRODUCTION: Electrostatic attraction of aerosolized particles to the inner
      walls of an aerosol holding chamber (HC) made from a nonconducting material can
      reduce medication delivery, particularly if there is a delay between actuation
      and inhalation. OBJECTIVE: Compare total emitted mass and fine-particle mass
      (mass of particles < 4.7 microm) of hydrofluoroalkane-propelled albuterol from
      similar-sized HCs manufactured from conductive material (Vortex), charge
      dissipative material (AeroChamber Max), and nonconductive material (OptiChamber
      Advantage, ProChamber, Breathrite, PocketChamber, and ACE), with and without
      wash/rinse pretreatment of the HC interior with ionic detergent, and with 2-s and
      5-s delays between actuation and inhalation. METHODS: All the HCs were evaluated
      (1) directly from their packaging (with no wash/rinse pretreatment) and (2) after
      washing with ionic detergent and rinsing and drip-drying. We used an apparatus
      that interfaced between the HC mouthpiece and the induction port of an 8-stage
      Andersen cascade impactor to simulate a poorly coordinated patient, with delays
      of 2 s and 5 s between actuation and inhalation/sampling, at 28.3 L/min. RESULTS:
      With the 2-s delay, the delivered fine-particle mass per actuation, before and
      after (respectively) wash/rinse pretreatment was: AeroChamber Max: 23.8 +/- 4.8
      microg, 21.5 +/- 3.2 microg; Vortex: 16.2 +/- 1.7 microg, 15.5 +/- 2.0 microg;
      OptiChamber Advantage: 2.6 +/- 1.2 microg, 6.7 +/- 2.3 microg; ProChamber: 1.6 +/
      0.4 microg, 5.1 +/- 2.5 microg; Breathrite: 2.0 +/- 0.9 microg, 3.2 +/- 1.8
      microg; PocketChamber: 3.4 +/- 1.6 microg, 1.7 +/- 1.6 microg; ACE: 4.5 +/- 0.9
      microg, 5.4 +/- 2.9 microg. Similar trends, but greater reduction in aerosol
      delivery, were observed with the 5-s delay. Significantly greater fine-particle
      mass was delivered from HCs made from conducting or charge-dissipative materials
      than from those made from nonconductive polymers, even after wash/rinse
      pretreatment (p < 0.01). The fine-particle mass was also significantly greater
      from the AeroChamber Max than from the Vortex, irrespective of wash/rinse
      pretreatment or delay interval (p < 0.01). CONCLUSION: HCs made from electrically
      conductive materials emit significantly greater fine-particle mass, with either a
      2-s or 5-s delay, than do HCs made from nonconducting materials, even with
      wash/rinse pretreatment.

PMID- 16638161
TI  - Levalbuterol aerosol delivery with a nonelectrostatic versus a nonconducting
      valved holding chamber.
AB  - BACKGROUND: Hydrofluoroalkane-propelled levalbuterol (Xopenex) aerosol is a
      recently approved formulation for delivery via metered-dose inhaler for the
      treatment or prevention of bronchospasm in adults, adolescents, and children > or
      = 4 years of age who have reversible obstructive airway disease. Valved holding
      chambers (VHCs) made from conventional polymers are susceptible to accumulation
      of electrostatic charge, which can be minimized by prewashing with ionic
      detergent, but it may be desirable to be able to use the product straight from
      the package, without pretreatment, especially during an exacerbation. METHODS: We
      studied the performance of the AeroChamber Plus and AeroChamber Max VHCs in
      delivering hydrofluoroalkane-propelled levalbuterol. Both VHCs were prewashed,
      rinsed, and drip-dried before testing. The AeroChamber Max is manufactured from
      charge-dissipative material and was therefore also evaluated without prewashing.
      Aerosol samples were collected at 28.3 L/min with an Andersen 8-stage cascade
      impactor, per the procedure specified in Chapter 601 of the United States
      Pharmacopeia. RESULTS: The mean +/- SD fine-particle mass (mass of aerosol
      particles < 4.7 microm aerodynamic diameter) values were 33.5 +/- 1.4 microg and
      36.3 +/- 1.1 microg with the AeroChamber Max, without and with wash/rinse
      pretreatment, respectively, and 28.5 +/- 2.4 microg with the prewashed
      AeroChamber Plus. CONCLUSIONS: We think the small differences we observed are
      unlikely to be of clinical importance, given the inter-patient variability seen
      with inhaled drug delivery. The performance of the AeroChamber Max was
      substantially comparable whether or not it was prewashed.

PMID- 16638162
TI  - Progressive pulmonary infiltrates in a patient with ovarian cancer.
AB  - We present a case of organizing pneumonia associated with lymphangitic spread of
      ovarian carcinoma in a 60-year-old Hispanic female with progressive dyspnea,
      hypoxemia, and bilateral pulmonary infiltrates. The patient was treated with
      corticosteroids, and she had rapid clinical and radiographic improvement.
      Malignancy-associated organizing pneumonia has most often been reported in bone
      marrow transplant and breast-cancer patients receiving radiation therapy. Data
      regarding organizing pneumonia in association with other malignancies is quite
      limited.

PMID- 16638163
TI  - A review of the alpha-1 foundation: its formation, impact, and critical success
      factors.
AB  - Patient-advocacy organizations have proliferated because they can be an effective
      method to advance research and clinical care for those with the index condition,
      and can produce substantial benefits for the affected community, especially when
      the condition is uncommon. To clarify critical success factors in organizing a
      patient-advocacy organization and to provide a blueprint for others, including
      the respiratory-care advocacy community, this report examines features of one
      highly successful organization, the Alpha-1 Foundation, which is committed to
      helping those with the genetic condition alpha-1 antitrypsin deficiency. Features
      of the Alpha-1 Foundation that underlie its success include: consistently
      creating partnerships with key stakeholders, including the scientific and
      clinical communities, government, and pharmaceutical manufacturers; bringing
      passion to the cause (eg, by assuring that organizational leadership is provided
      by individuals affected by alpha-1 antitrypsin deficiency); and developing
      strategic business partnerships, as with a company that administers alpha-1
      antitrypsin treatment (so-called intravenous augmentation therapy) and employs
      individuals with alpha-1 antitrypsin deficiency. Funds allocated by the company
      help to underwrite the foundation's research-funding commitment. The foundation
      also recruits and retains talent, including alpha-1 patients, to leadership roles
      (eg, on the board of directors) and has a voluntary group of committed scientists
      and clinicians. We believe that attention to these factors can help assure the
      success of patient-advocacy groups.

PMID- 16638164
TI  - Risk factors for hospitalization due to respiratory syncytial virus infection
      among infants in the Basque Country, Spain.
AB  - This study analysed the role of several risk factors for hospitalization due to
      community-acquired, respiratory syncytial virus (RSV) infection. The risk factors
      detected in infants hospitalized for RSV infection in the first 24 months of life
      were compared with those in the general infant population in our region. There
      were 361 episodes of hospitalization in 357 infants. Eighty per cent of the
      infants did not present underlying conditions for severe RSV infection and only
      10 (3%) were candidates for palivizumab prophylaxis. In multivariate analysis,
      birthweight of <2500 g was independently associated with hospitalization for RSV
      infection and was the most commonly detected medical risk factor. Other risk
      factors were maternal age at delivery <25 years, birth in the second half of the
      year, prematurity, suburban residence and congenital heart disease. In
      conclusion, together with well-known risk factors, we found that low birthweight
      was an independent factor for severe RSV infection.

PMID- 16638165
TI  - Changing epidemiology of bacterial meningitis among adults in England and Wales
      1991-2002.
AB  - We examined the epidemiology of community-acquired bacterial meningitis among
      adults in England and Wales between 1991 and 2002. Among 3169 cases,
      meningococcal infection was predominant among young adults and pneumococcal
      meningitis among older adults. Whilst infection due to most causes decreased, the
      incidence of tuberculous (TB) meningitis doubled over the 12 years. The mortality
      rate among meningococcal and pneumococcal infections fell from 0.45/10(5) to
      0.31/10(5) (P=0.0001). This study demonstrates important changes in the
      epidemiology of bacterial meningitis among UK adults. Improvements in clinical
      management, childhood vaccination programmes and the re-emergence of tuberculosis
      are likely to be drivers of these changes.

PMID- 16638166
TI  - Risk factors for Salmonella Enteritidis and Typhimurium (DT104 and non-DT104)
      infections in The Netherlands: predominant roles for raw eggs in Enteritidis and
      sandboxes in Typhimurium infections.
AB  - Since 1996 Salmonella Typhimurium DT104 salmonellosis has increased in The
      Netherlands. This prompted a case-control study of risk factors for salmonellosis
      to inform transmission routes for this phage type. Cases were laboratory
      confirmed patients with a Salmonella infection and controls were selected from
      population registries by frequency matching for age, sex, degree of urbanization
      and season. Cases and controls received a questionnaire on risk factors. Of the
      1171 cases, 573 (49%) responded: 245 S. Enteritidis and 232 S. Typhimurium cases
      (both DT104 and non-DT104), of which 58 were DT104. Of the 10250 controls, 3409
      (33%) responded. Use of H2 antagonists [odds ratio (OR) 4.4, 95% CI 1.6-12.2] and
      proton pump inhibitors (OR 4.2, 95% CI 2.2-7.9), consumption of raw eggs (OR 3.1,
      95% CI 1.3-7.4) and products containing raw eggs (OR 1.8, 95% CI 1.1-3.0) were
      associated with endemic S. Enteritidis infection. Risk factors for endemic S.
      Typhimurium infection were use of proton pump inhibitors (OR 8.3, 95% CI 4.3
      15.9), occupational exposure to raw meat (OR 3.0, 95% CI 1.1-7.9), playing in a
      sandbox (for children aged 4-12 years) (OR 2.4, 95% CI 1.6-3.7), consumption of
      undercooked meat (OR 2.2, 95% CI 1.1-4.1) and use of antibiotics (OR 1.9, 95% CI
      1.0-3.4). Use of proton pump inhibitors (OR 11.2, 95% CI 3.9-31.9) and playing in
      a sandbox (OR 4.4, 95% CI 1.8-10.7) were the only risk factors for S. Typhimurium
      DT104 salmonellosis. This study confirms known risk factors for salmonellosis.
      However, playing in a sandbox was a predominant new risk factor for S.
      Typhimurium salmonellosis in children [population attributable risk (PAR) 14%],
      and especially for S. Typhimurium DT104 (PAR 32%).

PMID- 16638167
TI  - Comparison of prevalence and risk factors for faecal carriage of the intestinal
      spirochaetes Brachyspira aalborgi and Brachyspira pilosicoli in four Australian
      populations.
AB  - This study examined the prevalence of the intestinal spirochaetes Brachyspira
      aalborgi and Brachyspira pilosicoli in different Western Australian (WA)
      populations. Faecal samples included 287 from rural patients with
      gastrointestinal symptoms, comprising 142 from non-Aboriginal and 145 from
      Aboriginal people; 227 from recent healthy migrants to WA from developing
      countries; and 90 from healthy non-Aboriginal individuals living in Perth, WA.
      DNA was extracted from faeces, and subjected to PCR assays for both species. B.
      pilosicoli-positive individuals were confined to the rural Aboriginal (14.5%) and
      migrant (15.0%) groups. B. aalborgi was detected at a lower but similar
      prevalence in all four groups: rural non-Aboriginals, 5.6%; rural Aboriginals,
      6.9%; migrants, 7.9%; controls, 5.6%. In migrants and Aborigines, the presence of
      B. pilosicoli and B. aalborgi was associated (P<0.001), suggesting that
      colonization by B. pilosicoli may be facilitated by colonization with B.
      aalborgi. Amongst the Aboriginal patients, logistic regression identified both
      spirochaete species as being associated with chronic diarrhoea, failure to thrive
      and being underweight. Both species may have pathogenic potential, but B.
      aalborgi appears more host-adapted than the opportunistic B. pilosicoli.

PMID- 16638168
TI  - Retinal bipolar cell types differ in their inventory of ion channels.
AB  - Bipolar cells were recorded in rat retinal slices to study the distribution of
      hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. Patch
      clamp whole cell measurements were combined with intracellular filling and
      recorded cells were morphologically identified. HCN channel isoforms HCN1-4 are
      differentially expressed in bipolar cells. Each bipolar cell type has a
      characteristic inventory of HCN channels. The combination of HCN channel currents
      and other voltage-gated currents can be used as a kind of "finger print" to
      electrophysiologically identify and classify bipolar cell types. Using this
      approach of combined electrophysiological and morphological classification we
      could identify a new ON-cone bipolar cell type.

PMID- 16638169
TI  - Origin of electroretinogram amplitude growth during light adaptation in pigmented
      rats.
AB  - We assessed the growth of the rat photopic electroretinogram (ERG) during light
      adaptation and the mechanisms underlying this process. Full field ERG responses
      were recorded from anesthetized adult Brown-Norway rats at each minute for 20 min
      of light adaptation (backgrounds: 1.8, 2.1, 2.4 log scotopic cd m(-2)). The rat
      photopic b-wave amplitude increased with duration of light adaptation and its
      width at 33% maximal amplitude narrowed (by approximately 40 ms). These effects
      peaked 12-15 min after background onset. The narrowing of the b-wave reflected
      steepening of the b-wave recovery phase, with little change in the rising phase.
      OP amplitudes grew in proportion to the b-wave. Inhibition of inner retinal
      responses using TTX resulted in a greater relative growth of b-wave and OP
      amplitude compared with fellow control eyes, and delayed the change in recovery
      phase by approximately 5 min. Inhibition of all ionotropic glutamate receptors
      with CNQX/D-AP7 delayed both rising and recovery phases equally (approximately 12
      ms) without altering b-wave width or the time course of adaptation changes. These
      outcomes suggest that inner retinal light responses are not directly responsible
      for b-wave amplitude growth, but may contribute to the change in its recovery
      phase during adaptation. A TTX-sensitive mechanism may help to hasten this
      process. The cone a-wave was isolated using PDA/L-AP4 or CNQX/L-AP4. A-wave
      amplitude (35 ms after stimulus onset) also increased with time during light
      adaptation and reached a maximum (130 +/- 29% above baseline) 12-15 min after
      background onset. B-wave amplitude growth in fellow control eyes closely followed
      the course and relative magnitude of cone a-wave amplitude growth. Hence, the
      increase of the cone response during light adaptation is sufficient to explain b
      wave amplitude growth.

PMID- 16638170
TI  - Spatio-temporal characterization of retinal opsin gene expression during thyroid
      hormone-induced and natural development of rainbow trout.
AB  - The abundance and spatial distribution of retinal cone photoreceptors change
      during thyroid hormone (TH)-induced and natural development of rainbow trout
      (Oncorhynchus mykiss). These changes are thought to allow the fish to adapt to
      different photic environments throughout its life history. To date, the ontogeny
      of rainbow trout cone photoreceptors has been examined using physiological and
      morphological approaches. In this study, we extended these observations by
      measuring opsin gene expression in retinal quadrants during natural and TH
      induced development. Gene expression during natural development was investigated
      in retinae from fish at both parr and smolt stages. The role of TH in modulating
      opsin gene expression was determined in TH-treated parr and control fish sampled
      after two, nine, and 22 days of treatment. Total RNA was isolated from each
      retinal quadrant and steady-state opsin mRNA levels were measured using reverse
      transcriptase real-time quantitative polymerase chain reaction (QPCR) analysis.
      Expression of ultraviolet-sensitive opsin (SWS1), rod opsin (RH1), middle
      wavelength-sensitive opsin (RH2), and long wavelength-sensitive opsin (LWS)
      transcripts vary spatially in the parr retina. Smolts, compared to parr, had
      downregulated SWS1 expression in all quadrants, lower LWS expression dorsally,
      higher RH1 expression nasally, and higher RH2 expression dorsally. In TH-treated
      parr, SWS1 opsin expression was downregulated in the nasal quadrants by two days.
      SWS1 displayed the greatest degree of downregulation in all quadrants after nine
      days of treatment, with an increase in short wavelength-sensitive (SWS2) and RH2
      opsin mRNA expression in the temporal quadrants. This study reveals that opsin
      genes display spatially significant differences within rainbow trout retina in
      their level of mRNA expression, and that regulation of opsin expression is a
      dynamic process that is influenced by TH. This is particularly evident for SWS1
      gene expression in parr following TH-induced and natural development.

PMID- 16638171
TI  - Neural mechanisms mediating responses to abutting gratings: luminance edges vs.
      illusory contours.
AB  - The discontinuities of phase-shifted abutting line gratings give rise to
      perception of an "illusory contour" (IC) along the line terminations. Neuronal
      responses to such ICs have been interpreted as evidence for a specialized visual
      mechanism, since such responses cannot be predicted from conventional linear
      receptive fields. However, when the spatial scale of the component gratings
      (carriers) is large compared to the neuron's luminance passband, these IC
      responses might be evoked simply by the luminance edges at the line terminations.
      Thus by presenting abutting gratings at a series of carrier spatial scales to cat
      A18 neurons, we were able to distinguish genuine nonlinear responses from those
      due to luminance edges. Around half of the neurons (both simple and complex
      types) showed a bimodal response pattern to abutting gratings: one peak at a low
      carrier spatial frequency range that overlapped with the luminance passband, and
      a second distinct peak at much higher frequencies beyond the neuron's grating
      resolution. For those bimodally responding neurons, the low-frequency responses
      were sensitive to carrier phase, but the high-frequency responses were phase
      invariant. Thus the responses at low carrier spatial frequencies could be
      understood via a linear model, while the higher frequency responses represented
      genuine nonlinear IC processing. IC responsive neurons also demonstrated somewhat
      lower spatial preference to the periodic contours (envelopes) compared to
      gratings, but the optimal orientation and motion direction for both were quite
      similar. The nonlinear responses to ICs could be explained by the same energy
      mechanism underlying responses to second-order stimuli such as contrast-modulated
      gratings. Similar neuronal preferences for ICs and for gratings may contribute to
      the form-cue invariant perception of moving contours.

PMID- 16638172
TI  - Interactions between rod and L-cone signals in deuteranopes: gains and phases.
AB  - The dynamics of interactions between rod and L-cone driven signals were studied
      psychophysically in two deuteranopic observers. Flicker detection thresholds for
      different ratios of rod to L-cone modulation were measured at temporal
      frequencies between 1 and 15 Hz. A model, which assumes that rod and L-cone
      driven signals are vector added, can describe the threshold data adequately. We
      found that up to about 8-10 Hz temporal frequency, rod and L-cone signals
      interact additively, whereas at higher frequencies the interaction is
      subtractive. Rod and L-cone signal strengths depend similarly on temporal
      frequency and are maximal between 3 and 5 Hz. The phase difference between rod
      and L-cone signals increases linearly with temporal frequency, indicating that
      their responses have a delay difference of about 20 to 30 ms, consistent with
      involvement of the faster rod pathway. The data would suggest a nearly complete
      additivity of the rod and cone driven signals when using flashed stimuli. But,
      literature data showed only partial additivity of the two, suggesting that
      different postreceptoral mechanisms are involved in the two tasks.

PMID- 16638173
TI  - Responses of the teleostean nucleus isthmi to looming objects and other moving
      stimuli.
AB  - Visually evoked extracellular neural activity was recorded from the nucleus
      isthmi (NI) of goldfish and bluegill sunfish. When moving anywhere within the
      right eye's visual field, three-dimensional checkered balls or patterns on a
      computer screen evoked bursts of spikes in the left NI. Object motion parallel to
      the longitudinal body axis gave responses that habituated markedly upon
      repetition, but movement into recently unstimulated regions of the visual field
      gave vigorous responses. Thus, while NI's response is not visuotopic, its
      habituation is. An object approaching the animal's body generated a rising spike
      density, whereas object recession generated only a transient burst. During the
      approach of a checkered stimulus ball, average NI spike density rose linearly as
      the ball-to-eye distance decreased and at a rate proportional to the ball's speed
      (2.5-30 cm/s). Increasing ball size (2.2-9.2 cm) did not affect the rate of
      activity rise at a given speed, but did increase overall activity levels. NI also
      responded reliably to expanding textures of fixed overall size. The results
      suggest that NI signals changes in motion of objects relative to the fish, and
      estimates the proximity of approaching objects.

PMID- 16638174
TI  - Immunolocalization of metabotropic glutamate receptors 1 and 5 in the synaptic
      layers of the chicken retina.
AB  - We have examined the distribution of metabotropic glutamate receptors (mGluRs) 1
      and 5 in the adult chicken retina using preembedding immuno-electronmicroscopy.
      Immunoreactivity for mGluRs 1 and 5 was found in both the outer plexiform layer
      (OPL) and the inner plexiform layer (IPL). For mGluR1, OPL labeling was observed
      at cone pedicles and horizontal and bipolar cell processes. In the IPL, mGluR1
      labeling could be found on bipolar cell terminals, as well as postsynaptic
      processes, including amacrine cell processes. Neither presynaptic nor
      postsynaptic elements were labeled at rod synapses. For mGluR5, OPL labeling was
      associated with cone pedicles as well as bipolar and horizontal cell processes.
      As for mGluR1, rod synapses were unlabeled. In the IPL, labeling for mGluR5 was
      found on bipolar cell terminals and amacrine cell processes. The presynaptic
      expression of these receptors in the OPL was confirmed at the light level by
      double-labeling experiments with SV2. The distributions of mGluRs 1 and 5
      indicate that they have the potential to regulate function in both synaptic
      layers. Furthermore, the similar expression patterns for these two receptors
      indicate that they might be co-expressed and thus have the potential to interact
      functionally.

PMID- 16638175
TI  - Temporal interactions in direction-selective complex cells of area 18 and the
      posteromedial lateral suprasylvian cortex (PMLS) of the cat.
AB  - Temporal interactions in direction-sensitive complex cells in area 18 and the
      posteromedial lateral suprasylvian cortex (PMLS) were studied using a reverse
      correlation method. Reverse correlograms to combinations of two temporally
      separated motion directions were examined and compared in the two areas. A
      comparison to the first-order reverse correlograms allowed us to identify
      nonlinear suppression or facilitation due to pairwise combinations of motion
      directions. Results for area 18 and PMLS were very different. Area 18 showed a
      single type of nonlinear behavior: similar directions facilitated and opposite
      directions suppressed spike probability. This effect was most pronounced for
      motion steps that followed each other immediately and decreased with increasing
      delay between steps. In PMLS, the picture was much more diverse. Some cells
      exhibited nonlinear interactions, that were opposite to those in area 18
      (facilitation for opposite directions and suppression for similar ones), while
      the majority did not show a systematic interaction profile. We conclude that
      nonlinear second-order reverse correlation characteristics reveal different
      functional properties, despite similarities in the first-order reverse
      correlation profiles. Directional interactions in time revealed optimal
      integration of similar directions in area 18, but motion opponency--at least in
      some cells--in PMLS.

PMID- 16638176
TI  - Sensitivity to visual motion in amblyopic macaque monkeys.
AB  - Amblyopia is usually considered to be a deficit in spatial vision. But there is
      evidence that amblyopes may also suffer specific deficits in motion sensitivity
      as opposed to losses that can be explained by the known deficits in spatial
      vision. We measured sensitivity to visual motion in random dot displays for
      strabismic and anisometropic amblyopic monkeys. We used a wide range of spatial
      and temporal offsets and compared the performance of the fellow and amblyopic eye
      for each monkey. The amblyopes were severely impaired at detecting motion at fine
      spatial and long temporal offsets, corresponding to fine spatial scale and slow
      speeds. This impairment was also evident for the untreated fellow eyes of
      strabismic but not anisometropic amblyopes. Motion sensitivity functions for
      amblyopic eyes were shifted toward large spatial scales for amblyopic compared to
      fellow eyes, to a degree that was correlated with the shift in scale of the
      spatial contrast sensitivity function. Amblyopic losses in motion sensitivity,
      however, were not correlated with losses in spatial contrast sensitivity. This,
      combined with the specific impairment for detecting long temporal offsets,
      reveals a deficit in spatiotemporal integration in amblyopia which cannot be
      explained by the lower spatial resolution of amblyopic vision.

PMID- 16638177
TI  - The number, morphology, and distribution of retinal ganglion cells and optic
      axons in the Australian lungfish Neoceratodus forsteri (Krefft 1870).
AB  - Australian lungfish Neoceratodus forsteri may be the closest living relative to
      the first tetrapods and yet little is known about their retinal ganglion cells.
      This study reveals that lungfish possess a heterogeneous population of ganglion
      cells distributed in a horizontal streak across the retinal meridian, which is
      formed early in development and maintained through to adult stages. The number
      and complement of both ganglion cells and a population of putative amacrine cells
      within the ganglion cell layer are examined using retrograde labelling from the
      optic nerve and transmission electron-microscopic analysis of axons within the
      optic nerve. At least four types of retinal ganglion cells are present and lie
      predominantly within a thin ganglion cell layer, although two subpopulations are
      identified, one within the inner plexiform and the other within the inner nuclear
      layer. A subpopulation of retinal ganglion cells comprising up to 7% of the total
      population are significantly larger (>400 microm2) and are characterized as giant
      or alpha-like cells. Up to 44% of cells within the retinal ganglion cell layer
      represent a population of presumed amacrine cells. The optic nerve is heavily
      fasciculated and the proportion of myelinated axons increases with body length
      from 17% in subadults to 74% in adults. Spatial resolving power, based on
      ganglion cell spacing, is low (1.6-1.9 cycles deg(-1), n = 2) and does not
      significantly increase with growth. This represents the first detailed study of
      retinal ganglion cells in sarcopterygian fish, and reveals that, despite
      variation amongst animal groups, trends in ganglion cell density distribution and
      characteristics of cell types were defined early in vertebrate evolution.

PMID- 16638178
TI  - Chromatic VEP assessment of human macular pigment: comparison with minimum motion
      and minimum flicker profiles.
AB  - To assess the effects of macular pigment optical density (MPOD) on isoluminant
      stimuli and to quantify MPOD electrophysiologically, MPOD distribution profiles
      were obtained in normal subjects using minimum motion and minimum flicker
      photometry. Isoluminance of VEP stimuli was determined using minimum flicker and
      tritan confusion lines were determined using a minimum distinct border criterion.
      Onset-offset and reversal VEPs to isoluminant red/green, blue/green, and subject
      specific tritan gratings of different diameters were recorded from the same 14
      subjects tested psychophysically. VEPs were additionally recorded to annular
      gratings. Chromatic VEP selectivity was assessed by Fourier analysis and as an
      index; onset negativity/(onset negativity + onset positivity). Peak MPOD varied
      between 0.2-0.8. Chromatic onset VEPs to all isoluminant 3-deg fields were
      predominantly negative. Larger blue/green and tritan stimuli elicited VEPs with
      additional positive, achromatic components; for 9-deg gratings, peak MPOD showed
      negative correlation with the power of the VEP fundamental (r = -0.70) and with
      the selectivity index (r = -0.83). Annular gratings elicited chromatic-specific
      B/G VEPs but only when isoluminance was determined for the annulus. Chromatic
      selectivity loss in VEPs to large B/G or Tritan gratings can be used to estimate
      subject-specific MPOD. An important implication is that isoluminant Tritan
      stimuli with short-wavelength components must be restricted in size in order to
      optimize koniocellular selectivity.

PMID- 16638179
TI  - Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in
      goldfish retina.
AB  - Goldfish cones contain CB1 receptors at the synaptic terminal, selectively
      accumulate 3H-anandamide, and contain fatty acid amide hydrolase
      immunoreactivity, and voltage-gated calcium and potassium currents are modulated
      by CB1 ligands (Yazulla et al., 2000; Fan & Yazulla, 2003; Glaser et al., 2005).
      These data suggest that a retinal mechanism may account for some of the
      psychophysical effects of cannabis. Here, we studied the effect of a cannabinoid
      agonist on cone light responses. Whole-cell patch-clamp recordings were made from
      cones in the isolated goldfish retina. Cones were stimulated with a spot of light
      of variable wavelength and intensities in combination with voltage-and current
      clamp protocols. Pharmacological manipulation was performed using the cannabinoid
      agonist WIN 55212-2 (10 microM). WIN had no effect on the absolute sensitivity of
      the cones or on the kinetics of the onset response. However, the light-offset
      response became faster, and the depolarizing overshoot was enhanced. Time
      constant of the offset response was reduced from 292 +/- 28 ms to 180 +/- 11 ms
      (n = 6) (P < 0.01) in the presence of WIN. Acceleration of the offset response
      was not affected by flash length from 200 ms to 10 s. This was found under
      current-clamp as well as under voltage-clamp conditions, indicating that the
      effect of WIN was mediated directly or indirectly by modulation of the cGMP-gated
      channels in the outer segment of the cones. The effects of WIN were not blocked
      by the CB1 antagonist SR141716A. With a train of "dark" flashes from a steady
      background, the photocurrent recovered toward baseline more quickly with WIN than
      in Control. In summary, cannabinoids speed up the dynamics of the
      phototransduction deactivation cascade in the cone outer segments. The functional
      consequence of this effect is to shorten the recovery time to the offset of
      bright flashes, perhaps resulting in an increase in contrast sensitivity.

PMID- 16638180
TI  - [Analysis of the different proteomes between the acute leukemia cells and normal
      white blood cells].
AB  - This study was aimed to analyze the different proteomes between human acute
      leukemia (AL) cells and normal white blood cells by proteomic technology in order
      to lay the basis for diagnosing AL and understanding the mechanism of
      leukemogenesis. The proteins from AL cells of 40 AL patients identified by FAB
      classification and proteins from normal lymphocytes and granulocytes of 20 normal
      volunteers were separated by two-dimensional electrophoresis (2-DE), and the
      differentially expressed proteins between the two groups were identified by both
      matrix assisted laser desorption/ionization-time of flight-mass spectrometry
      (MALDI-TOF-MS) and electronspray ionization (ESI)-MS/MS. The results showed that
      among the differentially expressed proteins between AL cells and normal
      lymphocytes and granulocytes, some proteins involved in the process of malignant
      transformation (such as Op18, NM23-H1), cell proliferation (such as PCNA) and
      apoptosis inhibition (such as tumor necrosis factor inhibitor protein) were found
      to be up regulated in AL cells. However, some proteins involved in
      differentiation and physiological functions of normal cells were down regulated
      in AL cells. It is concluded that there are many events involved in the process
      of leukemogenesis, expression of some proteins relating to the malignant
      transformation, cell proliferation and apoptosis inhibition are up-regulated in
      AL cells. The proteome analysis may provide a new approach to explaining the
      molecular mechanism underlying the pathogenesis of AL.

PMID- 16638181
TI  - [Effects of plumbagin on the human acute promyelocytic leukemia cells in vitro].
AB  - According to previous clinical experiences of the authors, plumbago zeylanica was
      effective against acute promyelocytic leukemia (APL). However, its effectiveness
      has never been proven experimentally or unequivocally clinically. This study was
      aimed to investigate the effects of plumbagin on the proliferation, cell cycle
      and apoptosis of APL cell line NB4 Cells. Cell inhibitory rates were detected by
      MTT colorimetric assay; morphologic changes were observed under light microscope
      and transmission electron microscope; apoptosis-inducing effects were determined
      by DNA gel electrophoresis, annexin V/PI double-stained and PI single-stained
      flow cytometry. The results demonstrated that 2-15 micromol/L plumbagin inhibited
      the proliferation of NB4 cells in a dose-dependent manner. The morphologic
      changes of cell apoptosis, such as chromsome condensation and apoptotic body
      formation, were observed by light microscope and transmission electron
      microscope. Cell cycle analysis showed that NB4 cells were blocked in G2/M phase
      of cell cycle. And plumbagin induced annexin V+/PI- cell increase and DNA
      fragmentation. There was a correlation between cell apoptosis rates and the
      concentrations of plumbagin in dose-dependent manner (P < 0.05). It is concluded
      that for the first time the present study shows that plumbagin can inhibit cell
      proliferation, block cell cycle and induce apoptosis of APL cell line NB4 cells.

PMID- 16638182
TI  - [Effect of diallyl disulfide on expression and secretion of VEGF in HL-60
      leukemic cells].
AB  - The study was aimed to investigate the expression of VEGF mRNA and VEGF protein
      in HL-60 cells treated with diallyl disulfide (DADS), and to explore the
      antileukemic mechanism of DADS in respect of VEGF production. Semi-quantitative
      RT-PCR and ELISA were used to detect the expression of VEGF mRNA and secretion of
      VEGF protein in HL-60 cell lines treated by DADS respectively. The results showed
      that the expression of VEGF mRNA and secretion of VEGF protein were found in HL
      60 cells. The expression of VEGF mRNA and secretion of VEGF protein in HL-60
      cells could be down regulated by treatment with 0.625, 1.25, and 2.5 microg/mL
      DADS for 48 and 72 hours and the effects had a dose dependent relationship (r >
      0.9, P < 0.01). The differences between DADS treated HL-60 cell groups and the
      control group were statistically significant (P < 0.01), there were also
      statistically significant differences among three DADS-treated HL-60 cell groups
      (P < 0.05). It is concluded that DADS effectively inhibits the proliferation of
      human leukemia cell line HL-60 cells; DADS exerts its antileukemic effects by
      reduction of the expression of VEGF mRNA and VEGF protein secretion.

PMID- 16638183
TI  - [Expressions of c-IAP2 and Smac gene in leukemia and their clinical
      significance].
AB  - To investigate the expressions of c-IAP2 and Smac in leukemia and their
      prognostic significance in adult patients with acute leukemia (AL), the mRNA
      expressions of c-IAP2 and Smac in 103 AL adult patients were measured by semi
      quantity reverse transcription polymers chain reaction (RT-PCR). Other 20 adults
      were selected as normal controls (NC), K562 and Kg-1alpha cell lines were
      employed as positive control. The results showed that the expressions of c-IAP2
      and Smac in de novo AL patients were higher than those in NC, while they
      decreased in patients at complete remission (CR). In relapsed patients, the
      expressions of c-IAP2 and Smac increased again. The mRNA expression of c-IAP2 and
      Smac in CML-CP were higher than that of NC, but no statistical significance was
      found (P > 0.05). In AL patients, the CR rate of c-IAP2+ and Smac+ cases were
      lower than those of c-IAP2- and Smac- cases. It is concluded that overexpression
      of c-IAP1 and Smac may play a synergic role in the pathogenesis of AL, and there
      is a positive correlation beween them. The c-IAP2 and Smac expressions are
      associated with remission rate in AL, while the patients with high level of c
      IAP2 or Smac have low remission rates. It seems that c-IAP2 and Smac serve as
      markers of poor prognosis in AL.

PMID- 16638184
TI  - [Identification of the isoform in type II receptor of transforming growth factor
      beta in patients with acute leukemia and its clinical significance].
AB  - Recent research indicates that TGF-beta and type II receptor (TbetaR-II) play an
      important role in the pathogenesis of tumor. A high frequency of abnormalities in
      TbetaR-II has been demonstrated in various cancers. To identify the mutation of
      TbetaR-II in patients with acute leukemia, the bone marrow samples from 6
      patients with acute leukemia and 11 normal individuals as control were detected
      by long-range RT-PCR. To detect a deletion in sequence of the TbetaR-IIgene, the
      PCR products were cloned to T vector and then sequenced. The results showed that
      there was existance of the isoform of TbetaR-II in 2 cases out of 6 patients with
      acute leukemia. These two patients had more poor prognosis than others. In
      conclusion, there was the isoform of TbetaR-II in partial patients with acute
      leukemia, and the isoform may be related with prognosis.

PMID- 16638185
TI  - [Expression of soluble GM-CSF-Ralpha in patients with acute myeloid leukemia].
AB  - To evaluate soluble GM-CSF-Ralpha expression in patients with acute myeloid
      leukemia (AML) and its clinic significance, plasma concentration of solGM-Ralpha
      in de novo 66 patients with AML was detected by enzyme-linked immuno-sorbent
      assay, and the relationship between solGM-Ralpha levels and various clinical
      parameters was analyzed. The result showed that the levels of solGM-Ralpha in
      plasma of patients with AML were significantly higher than that in plasma of
      normal controls; the lowest level of solGM-Ralpha was found in plasma of patients
      with AML-M3 (3897.75 +/- 2651.43 pg/ml), the highest level of solGM-Ralpha was
      observed in plasma of patients with AML-M5 (9990.92 +/- 6325.43 pg/ml). Patients
      with high level of solGM-Ralpha were generally accompanied with a distinct
      clinical picture, including higher counts of white blood cell and myeloid
      precursors, as well as higher expression of CD34, CD95 and CD116 antigen. It is
      concluded that the high level of solGM-Ralpha in plasma of patients may suggest
      AML poor prognosis and play a role in pathogenesis of leukemia, the GM-CSF and
      its receptor solGM-Ralpha needs further study.

PMID- 16638186
TI  - [Detection of fusion genes associated with specific translocations in acute
      leukemia patients with normal karyotypes by using multiplex RT-PCR].
AB  - This study was aimed to explore the usefulness of multiplex reverse transcription
      polymerase chain reaction (multiplex RT-PCR) in detection of fusion genes
      associated with specific translocations in acute leukemia (AL) patients with
      normal karyotypes. 37 AL patients with normal karyotypes were analyzed by
      multiplex RT-PCR. The results showed that 4 types of fusion genes such as
      PML/RARA, AML1/ETO, CBFbeta/MYH11, BCR/ABL were detected in 8 (21.6%) patients by
      multiplex RT-PCR. In conclusion, multiplex RT-PCR is useful in detection of
      fusion genes associated with specific translocations in acute leukemia (AL) with
      normal karyotypes and it would refine the karyotype analysis. When the normal
      karyotypes were detected in acute leukemia patients by conventional cytogenetic
      method, the multiplex RT-PCR should be performed for them.

PMID- 16638187
TI  - [Analysis of DEK-CAN fusion gene expression in acute myeloid leukemia patients
      with 6; 9 chromosome translocation].
AB  - This study was aimed to explore the relationship of 6; 9 chromosome translocation
      with DEK-CAN fusion gene expression in patients with acute myeloid leukemia (AML)
      and its clinical significance. Chromosome specimens were prepared by routine
      method after short-term culture of bone marrow cells; karyotype analysis was
      performed by R banding technique; the expression of fusion gene DEK-CAN was
      analyzed by RT-nested-PCR in mononuclear cells of bone marrow or peripheral blood
      of 4 AML patients, for 3 patients received allo-BMT out of 4 patients the dynamic
      follow-up was performed. The results indicated that t (6; 9) (p23; q34) was
      confirmed by chromosome karyotype analysis in the four AML patients. The DEK-CAN
      fusion gene was found during in all four de novo, relapsed and CR patients
      (100%). And the expression of DEK-CAN fusion gene enhanced apparently in de novo
      and relapsed patients, and weakened in CR patient. DEK-CAN mRNA was found in the
      three patients during 1-24 months after allo-BMT. Clinical data showed 2 patients
      relapsed and died after CR for 1-24 months; the other two patients received allo
      BMT got CR and still survive. It is concluded that DEK-CAN fusion gene is the
      molecular basis in pathogenesis of AML. The detection of DEK-CAN fusion gene is
      significant for diagnosis of AML, evaluation of curative effect, and predication
      of prognosis.

PMID- 16638188
TI  - [ZAP-70 expression in 24 patients with B cell chronic lymphocytic leukemia].
AB  - To explore the ZAP-70 expression in chronic lymphocytic leukaemia (CLL) and its
      relationship with other prognostic factors, the expressions of ZAP-70 protein and
      CD38 in bone marrow or peripheral blood of 24 patients with B-CLL were determined
      by four-color flow cytometry. The results showed that ZAP-70 was positively
      expressed in 37.5% of all B-CLL patients, 20% (3/15) patients in Binet A stage,
      and 66.7% in Binet B + C. The expression of ZAP-70 had significant difference
      between Binet A and Binet B + C (P < 0.05). CD38 was expressed in 29.1% of B-CLL
      patients and 3 out of these cases were in stage A, 2 out of 3 cases in stage A co
      expressed CD38 and ZAP-70. The expression of CD38 had no significant difference
      between Binet A and Binet B + C stage (P > 0.05). ZAP-70+ and CD38+ were both
      expressed in 83.3% of B-CLL patients (P < 0.05). It is concluded that ZAP-70
      protein can be routinely measured by flow cytometry in the laboratory. High
      expression of ZAP-70 is correlated with other prognostic factors such as clinic
      stage, chromosome abnormalities and CD38 in B-CLL.

PMID- 16638189
TI  - [Effect of PLK1 gene silence on cell cycle, proliferation and drug resistance in
      K562/A02 cells].
AB  - The study was purposed to investigate the effect of small interference RNA
      (siRNA) targeting Polo-like kinase 1 (PLK1) gene on cell cycle progression,
      proliferation and drug resistance in K562/A02 cells. siRNA plasmid vector
      specifically targeting PLK1 gene with enhanced green fluorescence protein (EGFP)
      was transfected into K562/A02 cells. Expressions of PLK1 mRNA and protein were
      assayed by RT-PCR and Western-blot; cell proliferation was evaluated by direct
      cell counting after trypan blue staining. Cell cycle and intracellular adriamycin
      (ADM) accumulation was determined by flow cytometry; 50% inhibition concentration
      (IC50) of ADM on K562/A02 cells was determined by MTT method. The results showed
      that, as compared with control cells, siRNA plasmid reduced PLK1 mRNA expression
      by (34.7 +/- 2.1)% for 24 hours and by (56.6 +/- 1.5)% for 48 hours, PLK1 protein
      significantly decreased simultaneously by (49.9 +/- 3.2)% and by (62.1 +/- 1.7)%.
      After being transfected for 24 and 48 hours, the rate of survival cells decreased
      by 30% and 59% respectively. Forty-eight hours after transfection, the ratio of
      K562/A02 cells at G2/M increased by 2.77-fold, at the same time, intracellular
      ADM accumulation increased and the relative efficiency of K562/A02 cells to ADM
      was 73.8%. It is concluded that PLK1 gene silence can inhibit K562/A02 cell
      proliferation, induce cell cycle arrest at G2/M, and increase intracellular ADM
      accumulation, so that enhance cell sensitivity to ADM.

PMID- 16638190
TI  - [Chronic myeloid leukemia onset with marked thrombocythemia].
AB  - This study was aimed to investigate the clinical, pathological and biological
      features of a special case of chronic myeloid leukemia (CML) with marked
      thrombocythemic onset. The morphological changes of cells were analyzed by using
      bone marrow smear and biopsy; Ph chromosome, a specific marker of CML, was
      assayed by conventional chromosomal analysis and fluorescence in situ
      hybridization, bcr/abl fusion gene was detected by reverse transcription
      polymerase chain reaction. The results indicated that CML mimicked essential
      thrombocythemia (ET) at presentation was relatively rare and might be
      misdiagnosed as ET, bone marrow smear and biopsy revealed, marked thrombocytosis
      and moderate leukocytosis; RT-PCR, FISH and conventional chromosomal analysis
      demonstrated the existence of Ph chromosome and bcr/abl fusion gene. This special
      CML could progress into accelerated phase or blast crisis. The megakaryocytes in
      Ph+ ET were smaller than normal ones and had typically hypolobulated round
      nuclei. Patients diagnosed as Ph+ ET might progress into CML and showed a high
      tendency to myelofibrosis and blastic transformation. It is concluded that the
      value of routine cytogenetical and molecular biological analysis in diagnosis for
      potential CML cases, which mimicked ET as in this presentation, is very
      distinctive, and the importance is magnified by the recent availability of
      imatinib, a specific inhibitor of the bcr/abl tyrosine kinase produced by the
      Philadelphia chromosome. Every case of "ET" should be tested for the Philadelphia
      chromosome and bcr/abl transcript.

PMID- 16638191
TI  - [Immunological screening for multiple myeloma-associated antigens and their
      bioinformatics analysis].
AB  - This study was aimed to screen the cell cDNA expression library of multiple
      myeloma HMy2 (MM HMy2) by using "serological analysis of cDNA expression library
      (SEREX)" technique. The obtained 30 positive clones were all sequenced, and
      analyzed by BLAST (basic local alignment search tool). The results indicated that
      6 known genes and 12 new MM-associated genes were obtained, part of which
      sequences were spliced by EST (expressed sequence tag) splicing. 6 known genes
      such as for ring finger protein 167, KLF10, TPT1 protein, p02 protein, cDNA
      FLJ46859 fis, DNMT1 methyltrasferase etc. have been demonstrated a certain
      relationship with other tumor's formation, progress and prognosis. The structures
      and functions of the new genes preliminarily analyzed and predicted by means of
      bioinformatics showed that MMSA-3, MMSA-8 and MMSA-11 encoding 215, 160 and 122
      amino acid residues respectively had the full open reading frames (ORF). All the
      new genes might be located at euchromosomes but MMSA-1 at sex chromosome. MMSA-4
      was highly similar to the protein controlling the transcription of tumor antigen,
      MMSA-5 might take part in cell phagocytosis, MMSA-7 might inactivated NF-kappaB,
      and MMSA-12 might be a lymphocytic cytoplasmic protein. The specificity of new
      genes such as MMSA-3 and MMSA-7 were higher, by a preliminary analysis using
      CrELISA. It is concluded that tumor antigens screened by this study can be used
      for early immunological diagnosis, surveillance of minor residual foci,
      assessment of prognosis, and preparation of tumor vaccine and so on.

PMID- 16638192
TI  - [Effect of arsenic trioxide on bone marrow stromal cells of patients with
      multiple myeloma].
AB  - To explore the effect of arsenic trioxide (As2O3) on growth and secretion of
      interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) of bone marrow
      stroma cells (BMSC) from the patients with multiple myeloma (MM). Specimens of
      bone marrow aspiration from MM patients were used to establish BMSC cultures.
      BMSC and human MM cell line CZ-1 were cultured together or alone in the absence
      or presence of As2O3 at various concentrations (1-20.0 micromol/L). Cell growth
      inhibition was assessed by MTT assay, cytokines in the culture supernatants were
      measured with ELISA. The results showed that As2O3 had cytostatic effect on CZ-1
      with fifty percent growth inhibition (IC50) for 48 hours at 2.3 micromol/L. As2O3
      did not inhibit the growth of BMSC. High levels of IL-6 and VEGF have been found
      in the culture supernatants of BMSC from MM patients. Cytokine production of BMSC
      treated with As2O3 significantly decreased as compared with controls (P < 0.05).
      Excitingly, even the increased cytokine production triggered by adhesion of MM
      cell and BMSC was also inhibited by As2O3. It is concluded that As2O3 has no
      inhibitory effect on cell growth of BMSC, but inhibit the production of IL-6 and
      VEGF by BMSC.

PMID- 16638193
TI  - [Effect of 2-methoxyestradiol on differentiation of primary myeloma cells].
AB  - In order to investigate the differentiation-inducing effect of 2-methoxyestradiol
      (2ME2), an estrogen derivative, on CD138+ (Syndecan-1) primary myeloma cells from
      7 patients with myeloma, primary myeloma cells from 7 patients were enriched by
      using CD138 immunomagenetic beads. The enriched CD138+ (Syndecan-1) myeloma cells
      treated with 0.5 micromol/L 2ME2 for 36 h and 72 hours were used to observe the
      differentiation changes with expression of CD49e and to quantitatively detect the
      light-chain secretion in the supernatants. The results indicated that 2ME2 caused
      morphological and immunophenotypic changes with light-chain secretion in the
      supernatant, and the typical features of differentiation of CD138+ (Syndecan-1)
      primary myeloma cells. CD138+ (Syndecan-1) myeloma cells became more and more
      mature in morphology, with decreased ratio of nucleus to plasma, disappearance of
      nucleoli, and pyknosis of chromatin. The result of detecting the expression of
      CD49e of CD138+ (Syndecan-1) myeloma cells showed the obvious up-regulation of
      CD49e expression after exposure to 2ME2 for 72 hours. Quantitative assay for
      light chain secretion in the supernatant of bone marrow CD138+ cells from
      patients showed remarkable increment at 72 hours. It is concluded that lower
      concentrations of 2-methoxyestradiol can induce differentiation of bone marrow
      CD138+ cells from multiple myeloma patients.

PMID- 16638194
TI  - [Tyrosine kinase inhibitor reverses adriamycin resistance mediated by cell
      adhesion in RPMI8226 cells].
AB  - To study the effects of tyrosine-kinase inhibitor STI571 on the adhesion of
      RPMI8226 cells to fibronectin (FN), cell adhesion mediated adriamycin-resistance
      and the Rac1 mRNA expression, the adhesion of RPMI8226 cells to fibronectin and
      drug resistance mediated by cell adhesion were determined by means of crystal
      violet staining and MTT assays respectively, Rac1 mRNA levels in RPMI8226 cells
      were examined by semi-quantitative RT-PCR. The results showed that STI571 could
      inhibit the adhesion of RPMI8226 cells to fibronectin. When RPMI8226 cells had
      been adhered to FN or BSA-coated wells for 1, 6 and 12 hours, the adhesion rates
      were (43.71 +/- 2.18)%, (55.63 +/- 1.56)%, and (63.42 +/- 2.46)% respectively.
      After treatment with STI571 20 micromol/L, the adhesion rates decreased to (15.12
      +/- 1.04)%, (17.58 +/- 1.32)% and (17.24 +/- 1.59)% respectively (P < 0.05). The
      experiment revealed that growth of RPMI8226 cells adhered to FN-coated plates had
      a significant advantage over growth on BSA-coated plates when exposed to
      adriamycin (Adr) for 1 hour followed by a 24-hour culture period, and the mean
      IC(50) value for FN-adhered cells was (1.46 +/- 0.04) micromol/L while mean
      IC(50) value for BSA control was (0.78 +/- 0.03) micromol/L (P < 0.05). Following
      treatment with 20 micromol/L STI571, the mean IC50 values for FN and BSA adhered
      cells were (0.81 +/- 0.05) micromol/L, (0.74 +/- 0.02) micromol/L respectively,
      there was no significant difference between them (P > 0.05). RT-PCR demonstrated
      that the relative Rac1 mRNA level (Rac1/GAPDH) in RPMI8226 cells was
      downregulated following being treated with 20 micromol/L STI571. It is concluded
      that STI571 can inhibit the adhesion of RPMI8226 cells to fibronectin, reverse
      cell adhesion mediated adriamycin-resistance, and downregulate Rac1 mRNA level.

PMID- 16638195
TI  - [Expressions of survivin, Bcl-2 and VEGF in patients with myelodysplastic
      syndrome and their relationship].
AB  - To determine the possible roles of survivin in the pathogenesis of
      myelodysplastic syndrome (MDS) and to explore the relationship between apoptosis
      and angiogenesis in MDS, the expressions of survivin, Bcl-2 and VEGF were
      detected in the BM cells of de novo patients with MDS, patients with AML and
      individuals of control by immunochemical staining and their relationship was
      analyzed. The results showed that the expression rate and integral of all the
      three proteins in the low-risk group of MDS, high-risk group of MDS and de novo
      acute myeloid leukemia patients gradually increased, in addition to expression of
      Bcl-2 in low-risk group of MDS and control group. The significant differences
      were observed in every two groups and there were positive relations between the
      every two proteins. It is concluded that survivin, Bcl-2 and VEGF are all
      involved in the pathogenesis of MDS, and related with the progression of this
      disease, the deregulated apoptosis and angiogenesis may be involved in the
      pathogenesis of MDS through interaction among three proteins mentioned above.

PMID- 16638196
TI  - [Apoptosis of in vitro cultured BMMNC from MDS patients induced by arsenic
      sulfide].
AB  - The aim of this study was to investigate the inhibition effect of arsenic sulfide
      (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore
      its possible cellular and molecular mechanisms. The apoptosis of MDS cells
      induced by As2S2 solution of different concentrations were studied with MTT, flow
      cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0
      0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2)
      after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk
      MDS cells presented typical features of apoptosis with a dose-dependent manner,
      the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after
      As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis
      ratio than that of BMMNC from control. It is concluded that BMMNC excessive
      apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows
      no inhibition effect on proliferation of MDS cells; high concentration of As2S2
      (1.5-50 mg/L) induces apoptosis of MDS cells.

PMID- 16638197
TI  - [Expression of SDF-1 gene in bone marrow mesenchymal stem cells of patients with
      myelodysplastic syndrome].
AB  - This study was aimed to investigate the expression level of stromal cell derived
      factor-1 gene (SDF-1) in bone marrow mesenchymal stem cells (MSC) of patients
      with myelodysplastic syndrome (MDS). The MSC from bone marrow samples of MDS
      patients were isolated, cultured and expanded, the morphology and immunophenotype
      of MSC were analyzed. The expression levels of SDF-1 and internal reference GAPDH
      in MSC of MDS patients were detected by real-time quantitative reverse
      transcriptase polymerase chain reaction (RQ-RT-PCR) method and were compared with
      expression levels of healthy donors. The results showed that the expression
      levels of SDF-1 in MDS patients were significantly different from those in
      healthy donors (1.53 +/- 0.92 vs 5.51 +/- 0.99) (P < 0.01). SDF-1 gene expression
      levels in bone marrow MSC of MDS patients were significantly higher than that in
      MSC derived from healthy donors. It is concluded that the abnormal expression of
      SDF-1 gene in MSC may influence the regulation of hematopoiesis of the bone
      marrow microenvironment in MDS patients and it is worthy of further investigation
      for new clue on etiological mechanism and treatment of MDS.

PMID- 16638198
TI  - [Expression of vascular endothelial growth factor in patients with aplastic
      anemia and its significance].
AB  - This study was aimed to investigate the expression of vascular endothelial growth
      factor (VEGF) in patients with aplastic anemia. The gene expressions of VEGF in
      mononuclear cells of bone marrow from 7 cases of aplastic anemia and 12 normal
      controls were detected by semi-quantitative reverse transcriptase polymerase
      chain reaction (RT-PCR). The expressions of VEGF in bone marrow from 20 cases of
      aplastic anemia and 20 normal controls were also determined by
      immunohistochemistry assay. The results showed that expression of VEGF mRNA was
      found in 2 out of 7 (28.57%) bone marrow of patients and in 10 out of 12 (83.33%)
      bone marrow of normal controls. The VEGF mRNA in patients with aplastic anemia
      was significantly lower than that in normal controls (P < 0.05). No patients with
      aplastic anemia showed immunohistochemical staining of VEGF in bone marrow, while
      5 out of 20 (25%) normal controls exhibited VEGF positive cells. Bone marrow of
      aplastic anemia patients contained less VEGF than that of normal persons (P <
      0.05). In conclusion, when compared with normal controls, VEGF expression
      decreased significantly in patients with aplastic anemia at gene transcription
      level and protein translation level, it may be related to the defect of
      angiogenesis and thus hematopoiesis in bone marrow of patients with aplastic
      anemia.

PMID- 16638199
TI  - [Expression of miR-28 in B cell lymphoma cell lines detected by solution
      hybridization].
AB  - microRNA (miRNA) is evolutionarily conserved, non-coding small RNA (19-25 nt)
      involved in post-transcriptional gene regulation. To further understand the
      biogenesis and functions of miRNA, and to quantify miRNA expression levels, the
      expression of miR-28 in B lymphoma cell lines was detected by solution
      hybridization and Northern blot, and their detected results were compared. The
      results indicated that detection of miR-28 by solution hybridization and Northern
      blot showed positive, but total RNA amount used for solution hybridization
      detection was significantly lower than that for Northern blot detection (5 microg
      vs 30 microg), signal of solution hybridization was stronger than that of
      Northern blot. It is concluded that the solution hybridization for detection of
      miR-28 in B cell lymphoma cell lines is a faster and more sensitive method as
      compared with standard Northern blot technique.

PMID- 16638200
TI  - [Regulatory effect of curcumin on p300 and HDAC1 in B-NHL cells].
AB  - The purpose of this study was to investigate the effect of curcumin on
      proliferation of B-NHL Raji cell line and explore the relationship between this
      effect and regulatory expression of p300 and HDAC1 transcription. The in vitro
      cultured Raji cells were treated with curcumin at various concentrations (6.25-50
      micromol/L) and at different time points (0, 6, 12, 24 and 48 hours), the
      inhibitory ratio of cell growth was measured by MTT assay, the cell apoptosis
      rate was detected by flow cytometry with Annexin V-FITC/PI double staining, the
      changes of p300 and HDAC1 mRNA expression and protein level in Raji cells were
      determined by RT-PCR and Western blot. The results showed that the curcumin could
      inhibit Raji cell proliferation in significant time-and concentration-dependent
      manners, IC50 at 24 hours was 25 micromol/L; the curcumin could induce apoptosis
      of Raji cells in concentration-dependent manner, apoptosis rate was 14.38%
      61.18%. The curcumin significantly inhibited activity and expression of p300 and
      HDAC1. At IC50 concentration, expression of p300 and HDAC1 mRNA and protein level
      decreased with time-dependent manner, difference between tested and control
      groups was significant (P < 0.05). It is concluded that the curcumin can inhibit
      proliferation of B-NHL Raji cells and promote apoptosis of those cells. Curcumin
      can inhibit the activity and expression of the transcriptional co-activator p300
      and HDAC1, which may be involved in its pharmacological mechanisms on B lymphoma
      cells.

PMID- 16638201
TI  - [IEMAD (modified MIME) therapy for refractory or relapsed non-Hodgkin's
      lymphoma].
AB  - The study was aimed to evaluate the effect of IEMAD (modified MIME) composed of
      isofosfamide, VM26 or VP16, methotrexate, cytarabine, dexamethasone or
      methylprednisolone, in treatment of refractory or relapsed non-Hodgkin's
      lymphoma. Twenty-five patients with refractory or relapsed non-Hodgkin's lymphoma
      (11 refractory NHL patients, 14 relapsed NHL patients) were treated with IEMAD
      regimen. The results showed that the complete remission rate was 24.0% (6/25) and
      the partial remission rate was 28.0%, having an overall response rate of 52%. The
      median survival duration was 13 months and the median duration of progression
      free survival was 8 months. The most frequent complications were gastrointestinal
      complaint (nausea, vomiting etc.) and myelosuppression. No treatment related
      mortality was found. It is concluded that the IEMAD (modified MIME) regimen may
      be a safe and effective regimen that can be used in treatment of patients with
      refractory or relapsed non-Hodgkin's lymphoma who did not respond to other
      regimens.

PMID- 16638202
TI  - [Early effect of amifostine in treating aged patients with idiopathic
      thrombocytopenia purpura].
AB  - The purpose of this study was to explore the effect of amifostine in treating
      aged patients with idiopathic thrombocytopenic purpura (ITP). Three aged ITP
      patients (one aged 88, one aged 75, another aged 65) were treated with amifostine
      over a period of 4 weeks for each. The results showed that the early positive
      responses were observed in all 3 aged patients after treatment with amifostine 5
      x 400 mg per week for 4 weeks, the recovery of platelet counts to normal level
      were found in 2 cases after 1 week and in 1 case after 2 weeks. Following 4
      months after stop of treatment with amifostine, the normal platelet counts still
      remains in all patients, no more blood transfusions, hormonal preparation and
      gamma-globulin were given. Amifostine has never been reported elewhere as to
      treat of aged ITP. In conclusion, amifostine has a good early therapeutic effect
      on aged ITP patients, but its clinical outcome of long-term still needs further
      evaluation.

PMID- 16638203
TI  - [Biological characteristics and ability of supporting hematopoiesis of bone
      marrow mesenchymal stem cells pre- and post-cryop-reservation].
AB  - This study was aimed to observe the biological characteristics of cryopreserved
      bone marrow mesenchymal stem cell (MSC) and to examine their abilities to support
      in vitro hematopoiesis. Bone marrow MSC were cryopreserved in -196 degrees C
      liquid nitrogen for 4 weeks (short term) and 9-15 months (medium term) with IMDM
      containing 10% DMSO, 40% fetal calf serum as cryoprotectant. The viability,
      proliferation, immunophenotype, in vitro differentiation and ability of
      supporting hematopoiesis of thawed MSC were investigated and compared with these
      of pre-cryopreserved MSC. The results showed that the cell viability were (93 +/-
      2.51)% and (90 +/- 3.75)% for MSC cryopreserved as long as 4 weeks or 9-15 months
      respectively. However, there were no changes detected, as compared with pre
      cryopreserved MSC in immunophenotype, abilities of proliferation and supporting
      colony forming of CFU-GM, CFU-E and CFU-GEMM. It is concluded that bone marrow
      derived MSC can be stored in liquid nitrogen for short-term (4 weeks) or medium
      term (9-15 months) without changes of abilities of proliferation, differentiation
      and hematopoiesis support.

PMID- 16638204
TI  - [Influence of human mesenchymal stem cells on cell proliferation and chemo
      sensitivity of K562 cells].
AB  - This study was aimed to compare K562 cell proliferation, chemo-sensitivity and
      alteration of MDR1 before and after adhesive culture with MSC, so as to evaluate
      the relationship between chemodrug-resistance of leukemia cells and hemopoietic
      microenvironment. K562 cell cultivated in suspension and adhesively cultivated
      with MSC were collected respectively and cell proliferation curves were drawn;
      the cell cycle was determined by flow cytometry; the effect of chemotherapy on
      cellular viability and apoptosis of K562 cell was investigated, the MDR1 gene
      expression was determined by RT-PCR. The results showed that K562 cells
      adhesively cultivated with MSC were inhibited and cells in G0/G1 increased (P <
      0.05), cells in S phase decreased (P < 0.05) and those in G0/G1 increased (P <
      0.01), compared with that cultivated in suspension. In process of daunomycin
      inducing apoptosis, K562 cell apoptosis in the adhesive culture with MSC was
      inhibited (P < 0.05). MDR1 gene expression in K562 cells was not induced or
      altered by adhesive co-cultivation. It is concluded that by co-culture of cell
      cell contact with MSC, growth suppression and induction of chemo-resistance of
      K562 cells take place. The mechanism, however, seems not relevant with MDR1.

PMID- 16638205
TI  - [Analysis of hematopoietic chimerism after non-myeloablative allogeneic
      peripheral blood stem cell transplantation].
AB  - The aim of this study was to analyze the hematopoietic chimerism after non
      myeloablative allogeneic peripheral blood stem cell transplantation (NAPBSCT). 28
      patients received NAPBSCT were evaluated. The conditioning regimen included FBC
      (fludarabine, busulphan, cyclophosphamide) +/- Ara-C. Peripheral blood was
      collected before and after transplantation in different periods. Semi
      quantitative assessment of hematopoietic chimerism was performed by short tandem
      repeat-polymerase chain reaction (STR-PCR), polyacrylamide gel electrophoresis
      (PAGE) and silver staining, and analyzed by Image Analysis System. The results
      showed that on day 30 after transplantation, one patient failed to engraft, but
      22 cases formed complete chimerism (CC) and 5 cases were of mixed chimerism. On
      day 7 after transplantation, the average percentage of donor cells was 74.71%.
      The time of dominance of the donor-specific allelic pattern preceded the recovery
      time of neutrophils and platelets. The incidence of aGVHD in group CC was
      significantly higher than that in group MC (P < 0.05). There was no significant
      difference in the incidence of cGVHD and disease relapse between group CC and
      group MC (P > 0.05). One patient relapsed in CC status without a transitional
      stage of MC. One patient with MC rejected grafts in early stage. 3 patients with
      MC transferred to CC and got complete remission after early implementation of
      therapy. It is concluded that sequential and quantitative detection of chimerism
      may be of great value to evaluate engraftment and to predict graft rejection,
      disease relapse and GVHD. Furthermore, it may provide a basis for early
      intervention treatment in the related complications.

PMID- 16638206
TI  - [Effect of different cytokine combinations on the expression of CD49d and CXCR4
      and ex vivo expansion of umbilical cord blood mononuclear cells].
AB  - This study was purposed to explore the effect of different cytokine combinations
      on the expansion of the mononuclear cells drived from umbilical cord blood (CB)
      ex vivo and expression of CXCR4 and CD49d on CD34+ cells after expansion. Human
      fresh CB mononuclear cells were cultured in serum-free and stroma-free medium
      containing different combinations of cytokine for 7 days. At day o and 7, the
      total cells were counted, CD34+ cells and CD34+CXCR4+, CD34+CD49d+ cells were
      assayed by flow cytometry, and CFU were determined. According to the different
      combinations of cytokine, experiments were divided into four groups: control, SF
      group (SCF + FL), SFT group (SCF + FL + TPO) and SFT6 group (SCF + FL + TPO + IL
      6). The results showed that the SF (SF group) combination supported only low
      expansion of total cells, CD34+ cells and CFU. The addition of TPO in SF group
      restored UCB stem/progenitors expansion to a higher level than that in SF group,
      while there was no difference between groups SFT and SFT6 (P > 0.05). The
      cytokine combinations in groups SF, SFT and SFT6 all could upregulate the
      expression levels of CD49d and CXCR4 on expanded cord blood CD34+ cells, but
      there were no significant differences between groups SF, SFT and SFT6 (P > 0.05).
      It is concluded that SCF + FL has no strong synergistic effects on primitive
      hematopoietic cells. TPO plays an important role in enhancing expansion of
      umbilical cord blood hematopoietic cells, while IL-6 only shows a neutral effect
      on it. SCF + FL + TPO combination not only promotes progenitor cells expansion
      but also upregulates the expression of CD49d and CXCR4 on CD34+ cells from cord
      blood.

PMID- 16638207
TI  - [Origin of mesenchymal stem cells in bone marrow of patients after allogeneic
      stem cell transplantation].
AB  - The aim of this study was to investigate the origin of bone marrow-derived
      mesenchymal cells in 34 patients who had received a sex-mismatched hematopoietic
      stem cells transplant (HSCT). The mesenchymal stem cells (MSC) from 34 patients
      were collected for test. The different passage MSC of patients were analyzed by
      flow cytometry (FCM) to reveal the cell surface antigen expression. The
      polymerase chain reaction (PCR) analysis of the amelogenin (AMEL) genes was used
      to detect donor cells from host cells. The cultured MSC were stained by
      fluorescence in situ hybridization (FISH) probes for chromosomes X (Xp11.1
      Xq11.1) and Y (Yq12) to distinguish donor cells from host cells. The results
      indicated that 31 out of 34 cases showed the confluent stroma and 24 out of these
      31 cases were successfully passaged for more than 5 generations which could be
      used for PCR and FISH analysis. According to FCM results the number of CD14+CD45+
      cells, which was regarded as monocyte/macrophage from the cultured MSC (passage
      5) was less than 0.04%. In PCR assay, the marrow-derived MSC from the passage 5
      were found to be of host origin. FISH assay demonstrated that marrow-derived MSC
      from the passage 5 were found to be of host origin up to 100%. It is concluded
      that the origin of MSC in bone marrow of patients after allogeneic stem cell
      transplantation was confirmed to be derived still from the recipients their own.

PMID- 16638208
TI  - [HSC transplantation-associated intestinal thrombotic microangiopathy: clinical
      pathological features, diagnosis criteria and treatment].
AB  - Thrombotic microangiopathy (TMA) is a lethal transplantation-associated
      complication which exactly likes acute intestinal graft-versus-host disease
      (GVHD) in the clinical manifestation. 373 consecutive patients with hematological
      diseases received family HLA matched or mismatched HCT from May, 2002 to July,
      2004. To analyse the clinical and pathological characteristics of TMA, 30
      patients who suffered from severe diarrhea and received colonoscopic examination
      and gut biopsy were retrospectively analyzed. The results indicated that 7
      patients originally diagnosed as gut GVHD showed the pathological evidence of
      enteric TMA. The incidence of TMA was 7 out of 30 specimen (23.3%). Pathological
      evidence of enteric TMA shown microvascular disorder characterized by thrombus in
      the capillary without infiltration of lymphocytes and perivascular hemorrhages in
      the mucosa, swelling and focal denudation of epithelial cells. All patients with
      TMA were associated with cytomegalovirus (CMV) antigenemia/disease. Among these
      patients, 4 cases, who only showed TMA without the evidence of gut GVHD
      pathologically, displayed treatment-resistant bloody diarrhea, renal failure,
      veno-occlusive disease, hemorrhagic cystitis, hemolytic anemia as well as
      thrombocytopenia. But the other 3 cases, with co-existence of both TMA and GVHD
      pathological characteristics had better treatment response. Survival analysis
      indicated that 3 patients with TMA-GVHD survived for 461 to 536 days but three
      out of four TMA patients died from VOD with liver failure as well as multiple
      organ failure during 101 to 254 days after HCT. In conclusion, to better diagnose
      those patients with severe and refractory diarrhea following HCT, pathological
      examination may indicate crux evidence to identify intestinal TMA from gut GVHD.
      Furthermore, this primary report has first evidenced that TMA and TMA-GVHD are
      two pathologically well-recognized subtypes with the difference between the
      pathological characteristics, treatment response and clinical outcomes.

PMID- 16638209
TI  - [Expression of survivin gene in NB4 cell line and cells of acute promyelocytic
      leukemia and its anti-apoptosis and clinical significance].
AB  - The study was aimed to detect expression rate of survivin gene in APL cell and to
      explore the relationship between its expression and clinical manifestation.
      PML/RARalpha and survivin mRNA expression were analyzed by using reverse
      transcriptase polymerase chain reaction (RT-PCR) technique. The results showed:
      (1) the survivin gene expression was detected in NB4 cell line. By treatment with
      ATRA, survivin mRNA expression in NB4 cell gradually decreased along with time
      delay and almost could not be detected at the 72th hour. (2) the positive and
      negative rate of survivin mRNA expression was 67% and 33% respectively, while in
      all 36 cases of de novo and relapse APL patients, the PML/RAR(alpha) fusion gene
      expression was positive. In 22 cases at remission stage, the PML/RARalpha fusion
      gene expression was negative, and the positive and negative rate of survivin mRNA
      expression was 36% and 64% respectively. The survivin mRNA expression positive
      rates in the de novo group, relapse group and PML/RARalpha fusion gene L-type
      positive group were obviously higher than those in remission period group (P <
      0.05) and were significantly lower than those in acute leukemia group (P < 0.05,
      < 0.001). (3) whether the survivin mRNA expression was positive or negative in 36
      cases of de novo and relapse APL patients, all the 36 cases could obtain complete
      remission. 4 APL patients with positive expression of survivin mRNA had DIC and
      serious infection (one patient died). The clinical symptom showed slight skin or
      mucosa bleeding, fever and asthenic in the patients with negative expression of
      survivin mRNA. When 2 APL patients with positive expression of survivin mRNA had
      been treated with ATRA, induction differentiation sign in their peripheral blood
      and bone marrow figures was not obvious. It is concluded that the survivin gene
      positive expression rate is lower in acute promyelocytic leukemia than that in
      any other types of leukemia and is related to clinical manifestation.

PMID- 16638210
TI  - Expressions of cyclin E2 and survivin in acute leukemia and their correlation.
AB  - Cyclin E2 is present in solid tumors, while its expression and clinical value in
      acute leukemia is unknown. This study was aimed to investigate the expression of
      cyclin E2 and survivin gene in bone marrow cells from patients with acute
      leukemia and their relationship. Reverse transcription polymerase chain reaction
      was used for detection of the expression of cyclin E2 and survivin mRNA in 84
      adult patients with acute leukemia which included 16 cases of relapse, 60 cases
      of de novo acute leukemia, 8 cases of continuously complete remission, and 20
      normal persons as controls. The results showed that (1) positive expression of
      cyclin E2 (70.24%) in acute leukemia patients was significantly higher than that
      (0%) in controls, positive expression of survivin (72.62%) in acute leukemia
      patients was higher than that (30%) in control. (2) the expression of cyclin E2
      positively correlated with that of survivin in acute leukemia patients. (3)
      remission rate in cyclin E2-positive patients (55.81%) was lower than that
      (88.24%) in cyclin E2-negative patients, the rate of cyclin E2 expression in
      relapse group was the highest among the three groups; while that in continuously
      complete remission group was the lowest among the three groups. (4) positive rate
      of cyclin E2 expression (59.32%) in patients with acute myelocytic leukemia was
      lower than that (96%) in patients with acute lymphocytic leukemia, no correlation
      between cyclin E2 expression and white blood cell counts of patients was found.
      It is concluded that the overexpression of cyclin E2 has been confirmed for the
      first time to positively correlate with the expression of the survivin in acute
      leukemia patients, and implicate the poor prognosis. Cyclin E2 may be used as a
      marker for examination of minimal residual disease.

PMID- 16638211
TI  - [Expression of apoptosis-related proteins in the human bone marrow hematopoietic
      cells treated by Panax Notoginosides].
AB  - The study was aimed to investigate the action of Panax Notoginosides (PNS,
      extracted from notoginseng herb) on the expression of the apoptosis-related
      proteins (Daxx, Fas) and transcription factors (NFkB, c-Rel) in the hematopoietic
      cells and to explore the mechanisms of supporting cells to survive. The colony
      formation of CFU-GM and CFU-E in human bone marrow was assayed in the presence of
      various concentrations of PNS. The viability of cells was assayed by trypan blue
      and the changes of cell morphology were observed with microscope. The Annexin-V
      positive cells were detected by FCM. Three lineages of human myeloid HL-60,
      erythroid K562, megakaryoid CHRF-288 and Meg-01 cells were incubated in addition
      of PNS (10 mg/L) for 14 days. The nuclear or cytoplasm protein of cells was
      extracted and analyzed by Western blot with monoclonal antibodies against Daxx,
      Fas or NFkB, c-Rel. The results showed: (1) the proliferation on hematopoietic
      progenitor cells (CFU-GM and CFU-E) and four cell lines was promoted by PNS; (2)
      after the four cell lines were promoted by PNS and hungered through wiping off
      the sera, the viability of the four cell lines was high without significant
      morphological change and neither the detection of Annexin-V positive cells; (3)
      the expression of Daxx and Fas protein could be inhibited by PNS. Western Blot
      showed that Daxx in four cell lines treated by PNS were 33.3-61.5% lower than
      that in untreated controls. The Fas protein was also descended in three cell
      lines of K562, CHRF-288 and Meg-01 by 33.3-71.4% respectively, while Fas protein
      in HL-60 cells was no detectable difference after PNS treatment. (4) The
      transcription factors NFkB and c-Rel protein could be increased by PNS. The NFkB,
      c-Rel protein were also enhanced in three cell lines of K562, CHRF-288 and Meg-01
      by (2.0-2.7) and (1.5-2.3)-fold respectively, while there were also no detectable
      difference in HL-60 cells after PNS treatment. It is concluded that PNS inhibites
      the expression of Daxx and Fas proteins, may decrease the apoptosis of the
      hematopoietic cells. The level of NFkB and c-Rel proteins can be enhanced by PNS,
      which not only stimulates the proliferation of cells, but also inhibits the
      activity of the waterfall of caspase and apoptosis of the hematopoietic cells.
      PNS may treat the disease with over-apoptosis of hematopoietic cells, as aplastic
      anemia.

PMID- 16638212
TI  - [Alteration of expression of survivin in HL-60 cells treated with
      chemotherapeutic drugs].
AB  - Survivin, a new member of the inhibitor of apoptosis protein (IAP) family,
      expressed in the most human cancers but not in terminally differentiated adult
      tissues, so survivin may be a target for tumor therapy. In addition, some
      scholars found that survivin expression is associated with the resistance in
      chemotherapy. To explore the relationship between survivin and drug-resistance,
      the alteration of survivin mRNA and protein of HL-60 cells treated with
      daunomycin (DNR), mitoxantrone (MIT) and arsenic trioxide (As2O3) was
      investigated, the expressions of survivin mRNA and survivin protein were detected
      on the first and third day by RT-PCR and Western blot, respectively. The results
      showed that survivin mRNA levels all decreased after the first day of treatment
      with drugs. It was decreased by 10% in DNR group, 40% (P < 0.01) in MIT group,
      and 25% (P < 0.01) in As2O3 group in comparison with control cells. In the third
      day, the survivin mRNA treated with DNR was up-regulated by 20% (P < 0.05),
      compared with the first day, and MIT was up-regulated by 65% (P < 0.01), but
      As2O3 was still down-regulated by 32% (P < 0.01). In Western blot, survivin
      protein level increased 14% after treated with DNR for three days, compared with
      the control cells, and 11% in MIT, but decreased by 82% in As2O3. It is concluded
      that after treatment with chemotherapeutic drugs, the survivin level descended at
      first day and then ascended obviously. This phenomenon may be associated with the
      resistance in chemotherapy for leukemia. On the other hand, As2O3 shows a
      different mechanism that may play a significant role to reverse resistance.

PMID- 16638213
TI  - [Anti-leukemia immunity induced by dendritic cells fused with L615 tumor cells].
AB  - This study was aimed to investigate the specific anti-L615 leukemia cell immunity
      induced by L615/DC fused cell vaccine in vivo and in vitro. BM-derived DCs were
      generated from bone marrow of 615 mice by culturing for 9 - 10 days in culture
      medium supplemented with GM-CSF and IL-4. Irradiated L615 tumor cells were fused
      with DC by using PEG to form fused cell vaccine, with which 615 mice were
      immunized. After immunization, the specific proliferation ability and
      cytotoxicity against L615 leukemia cells in vitro were examined by MTT and LDH
      methods. Anti-leukemia effect of fused cell vaccine in vivo was studied by
      observing the immunotherapy effects on L615 tumor-bearing mice. The results
      showed that fully mature and functional bone marrow-derived DC were obtained.
      L615/DC fused cell vaccine could elicit potent specific proliferation response of
      spleen T cells from immunized mice when contacting with the same antigen at the
      second time, and could also elicit the effective cytotoxic activity against L615
      leukemia cells in vitro, which were significantly different from other groups. In
      vivo the average survival time of the tumor-bearing mice received immunotherapy
      with L615/DC fused cell vaccine was 25.7 +/- 1 days, and one fourth of treated
      tumor-bearing mice survived for long time, but the mice of control group died
      all, their average of survival time was 17.5 +/- 1 days. The immunized mice
      survived with no evidence of recurrence when exposed to the second attack of
      lethal dose of living L615 cells 2 months later. It is concluded that L615/DC
      fused cell vaccine can improve the immunogenecity of L615 and induce effectively
      the specific anti-leukemia immunity against L615 leukemia cells to eliminate the
      residual leukemia cells, prolong the survival time and induce the immune memory
      to avoid the relapse. Thus, the fused cell vaccine may be an attractive strategy
      for malignance immunotherapy.

PMID- 16638214
TI  - [Detection of expression of Th1/Th2 cytokines in jurkat cell treated with gamma
      interferon by cytometric bead array].
AB  - In order to explore the value of gamma-interferon (IFN-gamma) in therapy of T
      lymphoid leukemia and role of cytometric bead array (CBA) method in detection of
      Th1/Th2 cytokines expression, the Jurkat cells were cultured for 48 hours in
      different concentration of IFN-gamma, the expressions of IL-2, IL-6, INF-gamma
      and TNF-alpha in culture supernatants were assayed by CBA method; CD25 expression
      was assayed by flow cytometry. The results showed that the expressions of IL-2,
      TNF-alpha were enhanced in INF-gamma dose-dependent way, and the expression of
      CD25 was also enhanced, but there was no expression of IL-6. It is concluded that
      Jurkat cells induced by IFN-gamma were able to express high-level of Th1 cytokine
      and IL-2 membrane receptor (CD25), and the CBA method can be used to exactly
      evaluate the dynamic change of Th1/Th2 cytokines.

PMID- 16638216
TI  - [Modified guanidine hydrochloride method for DNA extraction from cord blood used
      in HLA genotyping].
AB  - To compare two different methods for extracting genomic DNA from cord blood and
      to evaluate their applications for HLA genotyping, the genomic DNA from 72
      samples was extracted by guanidine hydrochloride (Gu * HCl) and modified
      guanidine hydrochloride, the DNA yield and purity were evaluated by
      spectrophotometry and detected by PCR with sequence-specific primers. The result
      showed that the genomic DNA was successfully isolated from whole blood by both
      methods. The modified Gu * HCl method used was better than Gu * HCl method as the
      modified method produces better quality of DNA and less ambiguous bands in PCR.
      It is concluded that modified Gu * HCl method has the advantages of low-cost,
      simple operation, high quality output and clear positive bands in HLA-genotyping,
      the modified method is optimal for extracting DNA from multiple samples of cord
      blood bank.

PMID- 16638215
TI  - [Effect of reduced glutathione as anti-leukemic immune adjuvant].
AB  - To investigate the reversal effect of reduced glutathione (GSH) on suppression of
      NK cells by reactive oxygen metabolites (ROM) in K562 cells, interleukin-2 (IL-2)
      or mononuclear cell (Mo) was added in cultured cell line of K562 cells and NK
      cells, the yield of ROM and K562 cell suppression rate were observed. Then the
      histamine dihydrochloride (DHT) or GSH was added in the mixed cultured cell
      lines, the ROM production and K562 cell suppression rate were observed. The
      results showed that the ROM yield increased from 33.17 +/- 5.08 U/L to 223.59 +/-
      9.41 U/L by IL-2, and K562 cell suppression rate increased from 65.56% to 85.89%
      by IL-2 (P < 0.01). The ROM yields were 389.79 +/- 43.83 U/ml, 456.74 +/- 42.77
      U/ml and 601.42 +/- 21.92 U/ml respectively, and K562 cell suppression rates were
      82.36%, 81.36% and 48.09% respectively, when Mo was added in the mixed cultured
      cell lines under ratios of E/Mo being 10/2, 10/5 and 10/10. When E/Mo was 10/2,
      DHT or GSH was added in the mixed cultured cell line ROM yield decreased from
      389.79 +/- 3.83 U/L to 50.21 +/- 2.4 U/L or -3.58 +/- 9.49 U/L (P < 0.05)
      respectively. With increase of concentration of DHT or GSH, the ROM yield in the
      mixed cultured cell line decreased (P < 0.05), the K562 cell suppression rate
      increased from 82.53% to 94.64% or 96.39% (P < 0.05), the more ROM yield, the
      less K562 suppression rate (P < 0.05). When E/Mo is 10/5 or 10/10, the ROM yield
      decreased by the high concentration of DHT or GSH (P < 0.05), but the K562 cell
      suppression rate not increased by every concentration of DHT or GSH. GSH was as
      effective as DHT in the reversing ROM and increasing K562 cell suppression rate.
      It is concluded that GSH may reverse ROM and increase K562 cell suppression rate,
      and GSH is as effective as DHT, but GSH has less side-effect than DHT. Therefore,
      GSH would be better antileukemia immune adjuvant.

PMID- 16638217
TI  - [Establishment of delta block matching technique].
AB  - To establish delta block HLA-matching technique, DNA was extracted from whole
      blood by salting-out method, delta block was amplified by polymerase chain
      reaction (PCR), and PCR product was detected by GeneScan. The results showed that
      delta block had polymorphism in 104 samples without sibship of the Han people
      from Zhejiang province. The range of DNA fragment length was 81-393 bp and could
      be divided into 4 groups: 81-118 bp, 140-175 bp, 217-301 bp, 340-393 bp. The
      numbers of DNA fragments were 6-32. It is concluded that the method of delta
      block matching is reliable and can be applied to select donors for the patients
      to be transplanted. It is the first time to get delta block data of the Han
      people in China.

PMID- 16638218
TI  - [Construction of rAAV2-GPIIb/IIIa vector and test of its expression and function
      in vitro].
AB  - This study was aimed to explore the possibility of rAAV2 vector-mediating gene
      therapy for Glanzmann' s thrombasthenia. The rAAV2-GPIIb/IIIa vector was
      constructed. The GPIIb/IIIa gene expression in mammal cell were examined by
      different methods, such as: detection of mRNA expression in BHK-21 cells after 24
      hours of infection (MOI = 1 x 10(5) v.g/cell) was performed by RT-PCR; the
      relation between MOI and quantity of GPII6/IIIa gene expression was detected by
      FACS after 48 hours of infection; GPIIb/IIIa protein expression in BHK-21 cells
      after 48 hours of infection (MOI = 10(5) v x g/cell) was assayed by Western blot,
      GPIIb/IIIa protein expression on cell surface was detected by immunofluorescence,
      and the biological function of expressing product was determined by PAC-1
      conjunct experiments. The results showed that GPIIb/IIIa gene expression in mRNA
      level could be detected in BHK-21 cells after 24 hours of infection at MOI = 1 x
      10(5) v x g/cell and the GPIIb/IIIa gene expression in protein level could be
      detected in BHK-21 cells after 48 hours of infection at MOI = 1 x 10(5) v x
      g/cell. In certain range, quantity of GPIIb/IIIa gene expression increased with
      MOI, but overdose of MOI decreased quantity of GPIIb/IIIa gene expression.
      Activated product of GPIIb/IIIa gene expression could combined with PAC-I, and
      possesed normal biological function. In conclusion, rAAV2 vactor can effectively
      mediate GPIIb and GPIIIa gene expressing in mammal cells, and the products of
      these genes exhibit biological function. This result may provide a basis for
      application of rAAV2 vector in Glanzmann's thrombasthenia gene therapy in
      furture.

PMID- 16638219
TI  - [Detection of promoter methylation of p16 gene in hematological malignant cell
      lines by nested methylation specific polymerase chain reaction].
AB  - This study was aimed to investigate the efficiency of modified methylation
      specific polymerase chain reaction i.e. nested methylation-specific polymerase
      chain reaction, used to detect the promoter methylation of p16 gene in six
      hematological malignant cell lines, and to explore the application in selection
      of hematological malignant cell lines with promoter hypermethylation, and make
      them to be an idel cell models for studying the relationship between gene
      methylation and expression. DNAs were denatured by NaOH and then were subjected
      to bisulfite modification and a nested-MSP was used to amplify the promoter
      region, nested MSP product of p16 gene promoter was analyzed and sequenced. The
      results showed that the hypermethylation of p16 gene was detected in CA46 and
      U266, however, Molt4, K562, HL-60 and Jurkat cell lines were unmethylated. In
      conclusion, p16 gene methylation in hematological malignant cell lines can be
      perfectly detected by nested-MSP method, which is simple, sensitive and specific
      for screening all kinds of hematological malignant cell lines with p16 gene
      methylated.

PMID- 16638220
TI  - [Cloning, expression and purification of human stem cell growth factor cDNA and
      its species-specificity in hematopoiesis].
AB  - Stem cell growth factor (SCGF) is an early-acting hematopoitic cytokine that has
      two isoforms including hSCGF with full length molecules and hSCGFbeta, 78 amino
      acids of which lost in the conserved calcium-dependent carbohydrate-recognition
      domain (CRD). It has been demonstrated that hSCGFbeta is strictly species
      specific in regulating he-matopoiesis. This study was aimed to explore whether
      human SCGF can exert synergistic stimulatory effect on heterogenous murine CFU-GM
      progenitor. Firstly, hSCGF cDNA was amplified from human fetal liver cDNA library
      by using two-step PCR. The hSCGF mature peptide coding sequence was subsequently
      placed at downstream of glutathione S-transferase (GST) sequence in GST gene
      fusion expression vector. The results indicated that there existed an additional
      60 kD protein compared with mock BL21 when the cells hosting recombinant plasmid
      were induced with IPTG at 37 degrees C. SDS-PAGE analysis demonstrated that the
      GST-hSCGF fusion protein mainly existed in insoluble form. When induced at low
      temperature (28 degrees C), the recombinant protein was mostly soluble. The GST
      fusion recombinant protein was subsequently purified by using affinity
      chromatography. The clonogenic assay revealed that, unlike hSCGFbeta, hSCGF had
      the granulocyte/macrophage promoting activity (GPA) for murine bone marrow GM
      progenitor. It is concluded that, in contrast to human SCGFbeta, the intact
      molecular hSCGF may have no species specificity, implying that CRD domain in
      human SCGFbeta does not directly bind to corresponding SCGF receptor, but may
      have certain biological function.

PMID- 16638221
TI  - [Construction of pEGFP-C1/U6-mediated plasmid expressing MDR1 shRNA].
AB  - To construct a plasmid expressing MDR1 short hairpin RNA (shRNA) mediated by
      pEGFP-C1/U6 vector, two coding sequences of 19 nucleotides were selected from
      MDR. Two pairs of oligonucleotides were designed for these two fragments. After
      annealing the formed double-stranded DNAs were ligated with plasmid pEGFP-C1/U6
      (pEGFP-C1 vector with U6 promoter). The plasmids producing MDR1 shRNA were
      constructed from the inverted motif containing 9 spacers and four Ts. The results
      showed that the constructed plasmids were named pEGFP-C1/U6/A and pEGFP-C1/U6/B,
      and the constructs were identified by restriction and sequence analysis, no any
      base mutation was observed. It is concluded that plasmids of pEGFP-C1/U6/A and
      pEGFP-C1/U6/B expressing MDR1 shRNA were successfully constructed, providing a
      highly effective method for reversing the multidrug resistance in clinic.

PMID- 16638222
TI  - [Establishment of murine cell line transfected with human CD14 gene].
AB  - This study was aimed to construct the CD14 eukaryotic expression vector,
      establish the transgeneic CD14 positive cell line in order to facilitate the
      establishment of a mouse model of antibody targeting therapy for human acute
      monocytic leukemia (AML-M(5)). Total RNA extracted from peripheral blood
      mononuclear cells was treated with RNAase-free DNAase, the human CD14 gene was
      cloned and sequenced through the RT-PCR and T-A clone techniques. Eukaryotic
      expressional vector pcDNA3.1(+)/CD14 was constructed by cleaving with double
      restriction endonuleases and ligating with T4 ligase. A murine melanoma cell line
      B16 was transfected with the pcDNA3.1(+)/CD14 recombinant with Superfect
      transfection reagent. Positive clones were selected by G418 and the expression of
      human CD14 on the transfectant was confirmed by flow cytometry (FCM). The results
      indicated that the sequence of the human CD14 cDNA cloned was exact to be same as
      the one from GenBank database. The recombinant pcDNA3.1(+)/CD14 was identified
      with double-enzyme cleaving. The expression of the human CD14 on the transfectant
      (B16/CD14) was confirmed by FCM. In conclusion, the murine cell line B16/CD14
      fransfected with human CD14 gene has been established which can be used for the
      study of human AML-M(5) antibody targeting therapy with mouse model.

PMID- 16638223
TI  - [Protective effect of vitamin C on protein activity in plasma during virus
      inactivation].
AB  - To determine whether addition of vitamin C (Vit C) to single-unit plasma could
      influence the efficacy of inactivating viruses and could maintain the activity of
      plasma proteins by methylene blue (MB)-light treatment. Vesicular stomatitis
      virus (VSV) Indiana strain was used as the indicating virus. Human plasma
      containing VSV was added with different concentrations of Vit C and final
      concentration 1 micromol/L MB and irradiated by fluorescence at an intensity of
      40,000 lx, samples were collected at different times for detection. Cytopathic
      effect was used to test the effect of virus inactivation. A segment of the
      nucleic acid encoding capsid protein of VSV was amplified with RT-PCR. Some
      methods, such as the Clauss method, the one-stage method,
      microimmunoelectrophoresis, were used to investigate the changes of plasma
      components. The results showed that when the VSV plasma was added with 240
      micromol/L Vit C and treated by MB-light irradiation for 60 min, the titer of VSV
      decreased by more than 8 lg TICD50/ml. Meanwhile, target segment amplification of
      VSV was also negative. The recovery rates of fibrinogen and coagulation factor
      VIII (FVIII: C) were 83.55% and 81.67% respectively, which had significant
      difference comparing with the routine MB-fluorescent light treatment. Most of
      plasma proteins were not affected significantly. No change in immunogenicity of
      these proteins was observed by using microimmunoelectrophoresis. It is concluded
      that virus inactivation is not influenced and plasma proteins are effectively
      protected by Vit C. Vit C can be used as a protector and is beneficial to
      improving the quality of plasma subjected to MB- photodynamic treatment.

PMID- 16638224
TI  - [High-dose etoposide with granulocyte colony-stimulating factor for mobilization
      of autologous peripheral blood stem/progenitor cells in patients with hematologic
      malignancies].
AB  - To explore the efficacy and safety of high-dose of etoposide with granulocyte
      colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem
      cells, 10 patients with hematologic malignancies including 6 patients with
      multiple myeloma and 4 with non Hodgkin' s lymphoma received an etoposide dose of
      1.6 g/m2. The total dose of undiluted etoposide was given on day 1 as a
      continuous intravenous infusion via a central vein for 10 hours. G-CSF 5
      microg/kg was used on day 3 and given daily subcutaneously until leukopheresis
      was completed. The results showed that leukopheresis was started at days 11
      (range 9-13 days) following etoposide therapy, the mean number of CD34+ cells
      collected in all 10 patients was 9.4 x 10(6)/kg (range 4.2 - 17.3 x 10(6)/kg), by
      an average of 2.6 leukophereses (range 1-4) times. Mobilization procedure that
      produced yields of greater than 4.0 x 10(6)/kg were achieved in every patient.
      Toxicity showed oropharyngeal mucositis, faucitis and urethritis respectively in
      3 patients. It is concluded that high-dose etoposide with G-CSF is an effective
      and safe mobilizing regimen for autologous peripheral blood stem progenitor cells
      in patients with hematologic malignancies.

PMID- 16638225
TI  - [Acute leukemia relapse of donor origin in two cases after haploidentical bone
      marrow transplantation].
AB  - To investigate the leukemia relapse of AL patients after HLA haploidentical bone
      marrow transplantation (HLA HBMT), 2 relapsed leukemia patients received HLA HBMT
      were studied, peripheral blood simples and bone marrow smear were examined,
      morphologic change of bone marrow cells was observed, while the HLA genotype and
      chromosome karyotye were analyzed by PCR and routine G-banding methods,
      respectively. The results indicated that the two cases were diagnosed primarily
      as acute lymphocytic leukemia (common cell subtype) and acute megakaryocytic
      leukemia, in which chromosome abnormalities or activation of protooncogene in
      leukemic cells were observed. The complete hematopuietie reconstitution of donor
      origin was obtained in these 2 cases after HLA HBMT, but the leukemic cells in
      these 2 leukemia patients were confirmed to be donor origin after relapse, their
      blood groups and HLA genotype were found to be originated from donor. These 2
      relapsed leukemia patients were diagnosed as acute lymphocytic leukemia (B cell
      subtype) and acute megakaryocytic leukemia. It is suggested that high-dose of
      immunosuppressive agents used in transplantation may contribute to leukemia
      relapse of donor origin in these patients. Abnormalities in hematopoietic
      microenvironment may be also involved in the leukemia development. Donor-cell
      leukemia after allogeneic hematopoietic stem cell transplantation can be an ideal
      model to investigate the related events in human leukemogenesis.

PMID- 16638226
TI  - [Effect of 5-hydroxtryptamine on megakaryocytopoiesis--review].
AB  - 5-hydroxtryptamine (5-HT, serotonin) has been recognized not only as a
      neurotransmitter and vasoactive agent, but also as a growth factor. 5-HT mainly
      binds to 5-HT(2) receptors or 5-HT(1) receptors on cell surface to stimulate cell
      proliferation through Ras or MAPK pathway in many cell types. It has been
      reported that 5-HT stimulates megakaryocytopoiesis via 5-HT receptors. The
      possible mechanism of 5-HT on the proliferation and differentiation of
      megakaryocytes (MK) has been discussed in this review article. In early stage of
      megakaryocytopoiesis, 5-HT may bind to 5-HT(2B) receptor on megakaryocytes, and
      promotes their proliferation and differentiation. In the late stage, 5-HT may
      involve in the platelet release procedure by inducing nitric oxide (NO) synthesis
      via 5-HT(2A) receptors. 5-HT can also antagonize the apoptotic effect induced by
      thrombospondin-1 (TSP-1) which is a platelet alpha granule protein and has
      synergic effect with platelet-derived growth factor (PDGF) to enhance
      megakaryocytes proliferation. Therefore, 5-HT is likely to be an important
      substance in the feedback regulation of thrombopoiesis. In this review the 5-HT
      and its receptors, 5-HT as cell growth factor, pathway of 5-HT stimulating cell
      proliferation and influance of 5-HT on MK-progenitor cells were summarized.

PMID- 16638227
TI  - [CD4+CD25+ regulatory T cells and their function in graft-versus-host disease-
      review].
AB  - As a functionally and phenotypically distinctive T cell subpopulation, CD4+CD25+
      regulatory T cells are anergic and retain their ability to suppress antigen
      driven response of CD4+CD25- cells in a contact-dependent manner or through a way
      of secreting immunosuppressive cytokines such as IL-10 and TGF-beta. Graft-versus
      host disease (GVHD) is one of the major complications following allogeneic
      hematopoietic stem cell transplantation (HSCT). Recently, some researches on the
      relationship between donor CD4+CD25+ regulatory T cells and GVHD severity
      produced two contradictory conclusions: one is CD4+CD25+ regulatory T cells that
      can prevent GVHD efficiently; the other is that GVHD is associated with the
      increased numbers of peripheral blood CD4+CD25+ regulatory T cells. The answer to
      this question will provide a new idea for clinic therapy of GVHD. In this review
      some new research progresses in the related area, such as the CD4+CD25+
      regulatory T cells, the phenotype, characteristics, immunoregulatory mechanisms
      of CD4+CD25+ regulatory T cells, as well as the relation of CD4+CD25+ with GVHD
      were presented.

PMID- 16638228
TI  - [Regulatory effects of Bmi-1 gene on self-renewal of hematopoietic stem cells-
      review].
AB  - Self-renewal of hematopoietic stem cells is vital for the sustained daily
      production of blood cells. The Bmi-1 gene is a putative oncogene belonging to the
      Polycomb group family. Recent studies have shown that the Polycomb-group gene Bmi
      1 is indispensable for regulation of self-renewal of normal and leukemic stem
      cells. The research progress on structure and function of Bmi-1 gene, and its
      role in self-renewal of hematopoietic stem cells was reviewed.

PMID- 16638229
TI  - [Research progress on trehalose used in lyophilization of blood cells--review].
AB  - Lyophilization is the best method for preservation of blood cells at present.
      Lyophilized blood cells could be stored at room temperature for long periods of
      time, while maintaining a high degree of viability. Lyophilized blood cells
      facilitates transportation and the costs are low. However, the membrane of blood
      cells is damaged and viability of blood cells is decreased in lyophilization.
      Trehalose has been shown to protect membrane, proteins and nucleic acids during
      freezing and desiccation. Now, researchers present a methor for loading blood
      cells with trehalose. In this paper, damage effect of lyophilization on blood
      cells, the mechanism of trehalose protection and the experimental studies on
      trehalose were reviewed.

PMID- 16638230
TI  - Global health care - bridging the gap.
AB  - The World Health Assembly has acknowledged that telehealth could play an
      important role in providing access to health care for populations at risk
      worldwide. The Cambodia Teleconsultation Programme or Village Leap Programme
      connects those in need of health care, with those willing to share their medical
      expertise. Telemedicine clinics are run every other week at one of two villages
      in northern Cambodia. The nurse is responsible for gathering medical information
      and transmitting it by email to physicians in the USA, and to the Sihanouk
      Hospital of Hope in Phnom Phen. Poorer countries do not and are not likely to
      have national telemedicine programmes in the near future. But as the experience
      in Cambodia shows, grass-root telemedicine programmes can make a difference. The
      need is great and we can no longer wait for governments to lead. Thoughtfully
      implemented telemedicine programmes providing medical education, health care and
      screening may change the health of the world.

PMID- 16638231
TI  - Principles of survey development for telemedicine applications.
AB  - Surveys can be used in the evaluation of telemedicine applications but they must
      be properly designed, consistent and accurate. The purpose of the survey and the
      resources available will determine the extent of testing that a survey instrument
      should undergo prior to its use. The validity of an instrument is the
      correspondence between what is being measured and what was intended to be
      measured. The reliability of an instrument describes the 'consistency' or
      'repeatability' of the measurements made with it. Survey instruments should be
      designed and tested following basic principles of survey development. The actual
      survey administration also requires consideration, for example data collection
      and processing, as well as the interpretation of the findings. Surveys are of two
      different types. Either they are self-administered, or they are administered by
      interview. In the latter case, they may be administered by telephone or in a face
      to-face meeting. It is important to design a survey instrument based on a
      detailed definition of what it intends to measure and to test it before
      administering it to the larger sample.

PMID- 16638232
TI  - Cultural aspects of telepsychiatry.
AB  - Telepsychiatry may involve working with clinicians, patients and systems of care
      that are both geographically and culturally distinct. In this context, culturally
      appropriate care is an important component of telepsychiatry. The outline for
      cultural formulation from the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV) provides general principles for addressing these issues. Two
      components of the outline are particularly relevant in telepsychiatry: (1) how
      the cultural background of patients (i.e. their cultural identity) influences
      their comfort with technology; and (2) the effect of cultural differences on the
      patient-provider relationship. Cultural differences between patient and provider
      are often highlighted in telepsychiatry by the patient and provider location
      (e.g. rural versus urban differences). Familiarity with the rural community and
      regular contact and feedback are important. Future research should examine the
      effect of telepsychiatry on patient-provider relationships, patient attitudes
      towards care and, most importantly, patient outcomes.

PMID- 16638233
TI  - A systematic review of telephone-based interventions for mental disorders.
AB  - To assess the effectiveness of telephone-based interventions for mental illness,
      a systematic search of the literature was conducted using the databases PsycINFO
      and PubMed, and the search engine Google Scholar. The search identified 14
      studies evaluating telephone-based interventions in the areas of depression (n =
      6), anxiety (n = 3), eating disorders (n = 3), substance use (n = 1) and
      schizophrenia (n = 1). Although these studies provide evidence that telephone
      interventions can be effective, the few studies conducted, small sample sizes and
      lack of randomized controlled trial methodology prevent firm conclusions from
      being drawn. The articles reviewed suggest that an effective telephone
      intervention includes clearly structured therapy sessions and homework tasks.
      However, further evidence using large-scale, randomized controlled trials must be
      obtained in order to inform government and telephone counselling agencies about
      the efficacy of telephone interventions.

PMID- 16638234
TI  - Telemedicine as a means of delivering cognitive-behavioural therapy to rural and
      remote mental health clients.
AB  - We explored the feasibility and acceptability of delivering cognitive-behavioural
      therapy (CBT) via videoconference to clients with depression and/or anxiety
      living in rural north Queensland. The study involved 15 mental health clients and
      their five case managers. First, each case manager was instructed in the use of
      telemedicine for clinical consultation, and given training in CBT. This was done
      via videoconference. Then the clients were introduced to telemedicine. Following
      six to eight intensive weekly sessions of CBT, there was improvement in certain
      clinical outcome measures (i.e. the Mental Health Inventory and the Health of the
      Nation Outcome Scale). There was a significant improvement (P<0.05 using a t
      test) in the client Mental Health Inventory scores before (mean = 109) and after
      treatment (mean = 148). However, in the absence of a control condition, it was
      not possible to conclude that the treatment had a specific effect on the
      disorders studied. Both clients and case managers found telemedicine
      consultations acceptable. Clients' ratings ranged from 3 to 4.5, while case
      mangers' ratings ranged from 3 to 5 ('average' to 'much better than average').

PMID- 16638235
TI  - Telestroke: a multi-site, emergency-based telemedicine service in Ontario.
AB  - A telestroke service was established in Ontario in 2002. Six neurologists on four
      campuses of two academic health centres of the University of Toronto participated
      in the call roster to support emergency physicians in two northern cities, North
      Bay and Sudbury. Videoconferencing units were provided in the hospitals and in
      the homes of the neurologists. PC workstations were used to access computed
      tomography (CT) images. In the first 34 months' operation, a total of 88 patient
      consultations were conducted. Twenty-six patients received tissue plasminogen
      activator (t-PA). Although the number of consultations was relatively low, the
      feasibility of telemedicine for acute stroke care was demonstrated. The economics
      remain to be explored. The telestroke model is a viable alternative to the
      provision of acute stroke care for communities that have CT scanners, but no
      access to a resident neurologist.

PMID- 16638236
TI  - Attitudes to the use of videoconferencing in general and specialist psychiatric
      services.
AB  - Mental health professionals and support staff were invited to complete a
      questionnaire about their experience of using videoconferencing. Our hypotheses
      were that mental health professionals in the UK do not have access to
      videoconferencing and do not believe that videoconferencing is appropriate for
      their work. Of the 134 people who completed and returned a questionnaire, 78
      worked in deaf mental health services and 56 worked in general mental health
      services. The majority were nurses (n = 33) or psychologists (n = 30). A total of
      109 respondents (81%) knew what videoconferencing was, but only 16 respondents
      (12%) had ever used it. The majority of the 32 respondents who knew the location
      of their nearest videoconferencing facility said that it could be accessed in
      less than 30 min. The 16 people who had previously used videoconferencing
      identified four different benefits of videoconferencing and eight different
      drawbacks. We conclude that mental health staff did not have adequate knowledge
      of, or access to, videoconferencing.

PMID- 16638237
TI  - Diagnostic value of written referral and/or images for skin lesions.
AB  - We examined whether it is possible for a dermatologist to diagnose benign and
      malignant skin lesions by telemedicine, given a comprehensive history and/or
      clinical images. A medical student recorded a standardized history and
      description of 109 skin lesions and took digital photographs of the presenting
      lesion(s) immediately prior to a normal outpatient dermatology consultation.
      About 52 dermatologists were invited to participate in online diagnosis. In all,
      38 took part and they were provided with the text and/or the image(s) online on a
      secure Website. When the images and text were provided, 53% of teledermatology
      diagnoses were the same as the face-to-face diagnosis. When images alone were
      provided, 57% of diagnoses were the same. When text alone was provided, 41% of
      diagnoses were the same. The relatively low diagnostic concordance may have been
      due to the inexperience of many teledermatologists and poor quality image display
      systems. The teledermatologists were less confident in their diagnoses than face
      to-face specialists, especially in the absence of images. The teledermatology
      management plan was more likely to include biopsy, excision or review than was
      the case at the face-to-face consultation. Teledermatology may result in an
      increase in follow-up appointments and surgical procedures.

PMID- 16638238
TI  - Patient satisfaction with tele-ophthalmology versus ophthalmologist-based
      screening in diabetic retinopathy.

PMID- 16638240
TI  - An unusual presentation of genitourinary schistosomiasis in a Caucasian woman in
      the UK.
AB  - A young woman who presented with loin pain and pyuria after a prolonged period of
      investigations and treatment, finally having a nephrectomy for non-functioning
      kidney, was revealed to have schistosomial infestation with an adult worm in the
      ureter. Unusually, she only developed bladder manifestations later.

PMID- 16638245
TI  - Diagnosis and diagnostic testing in primary care.

PMID- 16638246
TI  - Back pain-- reducing long-term problems.

PMID- 16638247
TI  - The diagnostic accuracy and utility of a B-type natriuretic peptide test in a
      community population of patients with suspected heart failure.
AB  - BACKGROUND: National guidelines suggest the use of natriuretic peptides in
      suspected heart failure but there have been no studies comparing assays in
      primary care. AIM: To test and compare the diagnostic accuracy and utility of B
      type natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide (NT
      proBNP) in diagnosing heart failure due to left ventricular systolic dysfunction
      in patients with suspected heart failure referred by GPs to one-stop diagnostic
      clinics. DESIGN OF STUDY: Community cohort, prospective, diagnostic accuracy
      study. SETTING: One-stop diagnostic clinics in Darlington Memorial and Bishop
      Auckland General Hospitals and general practices in South Durham. SUBJECTS: Two
      hundred and ninety-seven consecutive patients with symptoms and signs suggestive
      of heart failure referred from general practice. METHOD: The study measured
      sensitivity, specificity, positive and negative predictive values (PPV, NPV), and
      area under receiver operating characteristic curve for BNP (near patient assay)
      and NT proBNP (laboratory assay) in diagnosis of heart failure due to left
      ventricular systolic dysfunction. The NPV of both assays was determined as a
      potential method of reducing the number of referrals for echocardiography.
      RESULTS: One hundred and fourteen of the 297 patients had left ventricular
      systolic dysfunction (38%). At the manufacturer's recommended cut-off of 100
      pg/ml BNP gave a NPV of 82%. BNP performed better at a cut-off of 40 pg/ml with a
      NPV of 88%. At a cut-off of 150 pg/ml, NT proBNP gave a NPV of 92%. Using cut
      offs of 40 pg/ml and 150 pg/ml for BNP and NT pro-BNP, respectively, could have
      prevented 24% and 25% of referrals to the clinic, respectively. CONCLUSIONS: In
      this setting, NT pro-BNP performed marginally better than BNP, and would be
      easier to use practically in primary care. A satisfactory cut-off has been
      identified, which needs validating in general practice. NT pro-BNP could be used
      to select referrals to a heart failure clinic or for echocardiography. This
      process needs testing in real-life general practice.

PMID- 16638248
TI  - Predicting persistent disabling low back pain in general practice: a prospective
      cohort study.
AB  - BACKGROUND: Patients may adopt active and/or passive coping strategies in
      response to pain. However, it is not known whether these strategies may also
      precede the onset of chronic symptoms and, if so, whether they are independent
      predictors of prognosis. AIM: To examine, in patients with low back pain in
      general practice, the prognostic value of active and passive coping styles, in
      the context of baseline levels of pain, disability and pain duration. DESIGN OF
      STUDY: Prospective cohort study. SETTING: Nine general practices in north west
      England. METHOD: Patients consulting their GP with a new episode of low back pain
      were recruited to the study. Information on coping styles, pain severity,
      disability, duration, and a brief history of other chronic pain symptoms was
      recorded using a self-completion postal questionnaire. Participants were then
      sent a follow-up questionnaire, 3 months after their initial consultation, to
      assess the occurrence of low back pain. The primary outcome was persistent
      disabling low back pain, that is, low back pain at 3-month follow-up self-rated
      as >or=20 mm on a 100 mm visual analogue scale, and >or=5 on the Roland and
      Morris Disability Questionnaire. RESULTS: A total of 974 patients took part in
      the baseline survey, of whom 922 (95%) completed a follow-up questionnaire; 363
      individuals (39%) reported persistent disabling pain at follow-up. Persons who
      reported high levels of passive coping experienced a threefold increase in the
      risk of persistent disabling low back pain (relative risk [RR] = 3.0; 95%
      confidence interval [CI] = 2.3 to 4.0). In contrast, active coping was associated
      with neither an increase nor a decrease in the risk of a poor prognosis. After
      adjusting for baseline pain severity, disability, and other measures of pain and
      pain history, persons who reported a high passive coping score were still at 50%
      increased risk of a poor outcome (RR = 1.5; 95% CI = 1.1 to 2.0). CONCLUSION:
      Patients who report passive coping strategies experience a significant increase
      in the risk of persistent symptoms. Further, this risk persists after controlling
      for initial pain severity and disability. The identification of this low back
      pain subgroup may help target future treatments to those at greatest risk of a
      poor outcome.

PMID- 16638249
TI  - Sex inequalities in access to care for patients with diabetes in primary care:
      questionnaire survey.
AB  - BACKGROUND: Health experiences differ between men and women. The health services
      have focused their attention on gynaecological health problems in women, however
      women with non-gynaecological health problems could be unintentionally neglected.
      Given the increased prevalence of diabetes, the healthcare needs and experiences
      of women with diabetes are increasing. AIM: To determine the extent of sex
      inequalities in access to care for diabetes in primary care. DESIGN OF STUDY:
      Cross-sectional population-based questionnaire study. SETTING: Twenty-three
      general practices spread through 23 different primary care trusts in the former
      Trent Region, UK. METHOD: The study consisted of a random sample of 1,673
      patients with diabetes. Outcomes measured were odds ratios adjusted for age for
      measures of physical access to the GP's surgery; ease of obtaining appointments;
      access to primary care professionals; levels of routine diabetes care received;
      barriers to physical activity, problems eating and psychological distress as
      measured by the 18 score Diabetes Health Profile. RESULTS: Women were less likely
      than men to report that they had talked to their GP or practice nurse about their
      diabetes in the previous 12 months and were less likely to report that they were
      able to book routine appointments at convenient times. Almost 40% of all patients
      with diabetes reported difficulty in visiting the GP's surgery for their diabetes
      care, and women were more likely to report difficulties in visiting the surgery
      than men. Women were more likely than men to be afraid to go out alone (7.9%
      versus 3.6%) and more likely to be housebound (6.8% versus 2.4%). Women had
      significantly higher scores for eating problems and barriers to physical activity
      than men. CONCLUSIONS: Women report more problems with access to diabetes care
      than men. If the ambitions of the National Service Framework are to be met, then
      positive action needs to be taken to improve access to care for women with
      diabetes.

PMID- 16638250
TI  - Posttraumatic stress disorder in primary care with special reference to
      personality disorder comorbidity.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a common and disabling
      disturbance in primary care. Few studies have been carried out in primary care
      samples and none have taken into consideration the association between PTSD and
      personality disorder. AIM: To describe prevalence and risk factors of PTSD and
      its comorbidity with personality disorder. SETTING: General practice centre in
      Valencia (Spain). METHOD: Patients who had experienced at least one traumatic
      event in their lives were selected from a random sample attending a primary
      healthcare centre in Valencia and blindly assessed by trained professionals.
      Patients suffering from PTSD were compared with those who were not. PTSD and
      personality disorder diagnoses were established using CIDI and SCID-II interviews
      respectively. Sex, age at the time of experiencing trauma, frequency,
      multiplicity and type of trauma, dissociative symptoms, personality disorder and
      severity of PTSD were subjected to multivariate analysis to estimate the
      probability of developing PTSD and its duration. RESULTS: Life prevalence rate
      was 14% and current prevalence 9%. Dissociative symptoms and personality disorder
      were significantly associated with PTSD. Cluster analysis based on age, frequency
      and type of trauma revealed the existence of one subgroup composed mainly of
      women who had experienced frequent body-contact trauma at an early age, developed
      severe PTSD and suffer from a variety of personality disorders, particularly
      paranoid personality disorder. Time to the complete disappearance of symptoms was
      only explained by the initial severity of PTSD. CONCLUSION: PTSD is a frequent
      disorder in general practice and it is often associated with personality
      disorder. Women who experienced high frequency body-contact traumatic events at
      an early age often suffer from personality disorder and present a particularly
      severe form of PTSD deserving referral to specialised care.

PMID- 16638251
TI  - Urgent GP referrals for suspected lung, colorectal, prostate and ovarian cancer.
AB  - BACKGROUND: The UK urgent cancer referral guidance was introduced between 1999
      2000. There is a dearth of literature relating to the effectiveness in detecting
      cancer of urgent suspected cancer referrals and general practitioners' compliance
      with the guidance. AIMS: This paper aims to determine the diagnostic yield from
      urgent referrals for suspected colorectal, lung, ovarian and prostate cancer, and
      the proportion of patients with cancer who were urgently referred. Secondary aims
      are to determine the association of these findings with age, ethnicity, sex and
      marital status, and to determine the proportions of patients who fulfilled the
      urgent referral criteria. DESIGN: Detailed notes analysis of all urgent referrals
      and all cancer diagnoses. SETTING: One hospital trust in England. METHOD: Data
      regarding all urgent referrals and all cancer diagnoses were obtained from one
      hospital trust over a 2-year period. Data analysis was undertaken to determine,
      diagnostic yields and their association with sociodemographic factors, trends
      over time and fulfilment of the guidance. RESULTS: The percentages of urgent
      referrals diagnosed with cancer were colorectal 11%, lung 42%, ovarian 20%, and
      prostate 50%. The percentages of patients with cancer referred urgently were
      colorectal 21%, lung 23%, ovarian 24%, and prostate 32%. Patients who were
      urgently referred without cancer were younger than those with cancer for all but
      prostate. There were no significant differences by sex, marital status or
      ethnicity. For patients with cancer there were no differences for any
      sociodemographic factors in whether or not they were referred urgently.
      CONCLUSIONS: The predictive power of the referral guidance as a marker for cancer
      is low, resulting in significant numbers of patients being urgently referred
      without cancer. A large majority of patients not diagnosed with cancer through
      the urgent referral route did fulfil the criteria for urgent referral, suggesting
      that with more widespread use of the guidance the diagnostic yields will be
      higher. This has implications for patients, on hospital diagnostic systems, and
      for patients presenting through other pathways.

PMID- 16638252
TI  - A profile of communication in primary care physician telephone consultations:
      application of the Roter Interaction Analysis System.
AB  - BACKGROUND: Telephone consultations are a part of everyday practice, there is
      surprisingly little research on the subject. AIM: To describe the variation of
      consulting skills within a body of telephone consultations in primary care,
      highlighting the performance of one method of assessing the process of the
      consultation-- the Roter Interaction Analysis System-- with telephone
      consultations. DESIGN OF STUDY: Cross sectional study of 43 recordings of
      telephone consultations with GPs. SETTING: One rural county in the Midlands.
      METHOD: Recordings were made of 8 GPs, purposively selected for maximum variance
      in one region of the UK. Forty-three consultations were coded using the Roter
      Interaction Analysis System. From the descriptive categories, six composite
      categories were compiled reflecting a number of domains of interaction in a
      consultation: rapport, data gathering, patient education and counselling,
      partnership building, doctor dominance and patient-centredness. Analysis of
      variance was undertaken to explain variations between consultations for the
      different domains. Comparison was made to findings from similar work for face-to
      face consultations. RESULTS: These telephone consultations feature more
      biomedical information exchange than psychosocial or affective communication.
      Length of interaction accounts for much of the variation seen between
      consultations in the domains of rapport, data gathering, patient education and
      counselling and partnership. Male doctors are more patient centred in this study.
      There is the suggestion of more doctor dominance and a less patient-centred
      approach when comparisons are made with previous work on face-to-face
      consultations. CONCLUSIONS: Although the telephone is increasingly being used to
      provide care, this study highlights the fact that telephone consultations cannot
      be taken as equivalent to those conducted face to face. More work needs to be
      done to delineate the features of telephone consultations.

PMID- 16638253
TI  - Limited impact on endoscopy demand from a primary care based 'test and treat'
      dyspepsia management strategy: the results of a randomised controlled trial.
AB  - BACKGROUND: Helicobacter pylori testing has been suggested as an alternative to
      endoscopy for young patients with dyspepsia. Secondary care studies have
      suggested that demand for endoscopy among this group could be reduced by up to
      74%. However, the effect of H. pylori testing in the primary care setting, where
      the majority of dyspepsia is managed, is unclear. AIM: To determine the effects
      of providing a H. pylori serology service for GPs upon demand for open access
      endoscopy. DESIGN OF STUDY: A prospective randomised controlled trial. SETTING:
      Forty-seven general practices in Gloucestershire. METHOD: General practices were
      stratified by endoscopy referral rate and randomised into two groups. The
      intervention group was provided with access to H. pylori serology testing and
      encouraged to use it in place of endoscopy for patients aged under 55 years with
      dyspepsia. Endpoints were referral for endoscopy and serology use. RESULTS: There
      was a significant reduction in referrals for endoscopy in the intervention group
      compared to the control group: 18.8% (95% confidence interval = 5.0 to 30.6%; P =
      0.009). CONCLUSIONS: Providing GPs with H. pylori serology testing reduced demand
      for open access endoscopy, but by less than previous studies had predicted.

PMID- 16638254
TI  - Assessing blood pressure control in patients treated for hypertension: comparing
      different measurements and targets.
AB  - We examined how different methods and definitions of blood pressure affect the
      achievement of targets in general practice. There was a wide range in the
      proportion of treated patients achieving the different target levels recommended
      by the National Institute for Health and Clinical Excellence, British
      Hypertension Society and the general medical services contract. Among non
      diabetic patients this ranged from; 10-37% (average office), 15-39% (standardised
      nurse measurement), 11-49% (last recorded) and 31-56% (ambulatory blood
      pressure). Defining targets without a clear definition of how blood pressure
      should be measured is largely meaningless and ignoring ambulatory blood pressure
      results in many patients being classified incorrectly as failing to achieve
      targets.

PMID- 16638255
TI  - Discovering the research priorities of people with diabetes in a multicultural
      community.

PMID- 16638256
TI  - The fairy godmother has spoken.

PMID- 16638257
TI  - Up-to-date findings show change in acute otitis media consultation trend.

PMID- 16638258
TI  - Business management in general practice should feature in the nMRCGP.

PMID- 16638259
TI  - Low breastfeeding rates and milk insufficiency.

PMID- 16638260
TI  - Genetic epidemiology and primary care.

PMID- 16638261
TI  - Polycystic ovary syndrome.

PMID- 16638265
TI  - Protecting patient confidentiality in telephone consultations in general
      practice.

PMID- 16638266
TI  - A taxonomy of general practice.

PMID- 16638271
TI  - [Advance with times to create the superior journal].

PMID- 16638272
TI  - [Emphasizing the prevention and treatment of immune rejection after corneal
      transplantation].
AB  - Corneal transplantation is a major therapeutic method to recover the sight from
      corneal blindness, however, the immune rejection is still the major impact factor
      for graft failure. With the improvement of the medical care in our country,
      corneal transplantation has been increased continually. Therefore, reducing the
      complications and increasing the long-term transparency rate of the graft is an
      important mission for ophthalmologists. The key core of the corneal
      transplantation is to pay more attention to the follow-up and prevent the immune
      rejection. Three respects, including the current status and problems of corneal
      transplantation in China, the update immune rejection theory and the means of
      reducing the immune rejection of the corneal graft, and the methods to reduce the
      risk of blindness due to immune rejection, will be focused in this paper.

PMID- 16638273
TI  - [Sustained rapamycin drug delivery system in prevention of high risk corneal
      allograft rejection and neovascularization in rabbits].
AB  - OBJECTIVE: To evaluate the immunosuppressive and antiangiogenesis effects of
      rapamycin drug delivery system (RAPA DDS) in high risk rabbit model of
      penetrating keratoplasty (PK). METHODS: (1) RAPA DDS preparation: 50 mg of PGLC
      and 50 mg of RAPA were mixed as a RAPA drug delivery system. (2) High risk rabbit
      model: Corneal vascularization was induced in 45 New Zealand white rabbits (45
      eyes) by passing 5 - 0 silk sutures in corneal stroma in each quadrant. (3) 40
      rabbits with corneal neovascularization beyond three quadrants were received a
      unilateral 7 mm diameter central PK. The 40 were divided into four treatment
      groups: Group A, control group and received no therapy; Group B, 1 mg PGLC
      carrier was implanted in the anterior chamber; Group C, 1% RAPA eye drops was
      applied four times daily; Group D, 0.5 mg RAPA DDS was implanted in the anterior
      chamber. (4) Postoperative examination: The cornea allografts (opacity, edema and
      neovascularization) were examined by the slit-lamp biomicroscopy for ninety days.
      Rejection index (RI) and neovascularization index (NI) of these animal models
      were recorded. RAPA concentration in the aqueous humor was detected on 2, 4, 8
      and 12 weeks in group C and D after surgery; the expressions of IL-2R, MCP-1,
      Fas/FasL in samples were detected with in situ hybridization; TNF-alpha and VEGF
      were detected with immuno-histochemical technique three weeks after the operation
      in all groups. Histochemical method was carried out on the procured specimens of
      cornea, retina, liver and kidney at ninety days. RESULTS: (1) Allografts
      rejection: Mean survival times in 4 trial groups were (16.5 +/- 2.5), (16.0 +/-
      2.6), (47.1 +/- 13.2), (87.6 +/- 5.8) d respectively (P = 0.000). (2) Corneal
      neovascularization: Mean NI was 2.4 +/- 0.7, 2.1 +/- 0.5, 0.6 +/- 0.5, 0.3 +/-
      0.5 (P = 0.000) 2 weeks after the operation, and the NI value was 3.8 +/- 0.5,
      3.8 +/- 0.4, 0.8 +/- 0.7, 0.4 +/- 0.8 (P = 0.000) 12 weeks after the operation in
      groups A, B, C and D respectively. (3) RAPA concentration in aqueous humor: Mean
      RAPA concentration in aqueous humor was 10.7, 12.0, 9.2, 7.0 ng/ml in group D in
      the 2, 4, 8 and 12 weeks after the operation respectively. RAPA can not be
      detected in group C. (4) Cytokine expression: IL-2R, MCP-1, TNF-alpha and VEGF
      were overexpression in group A and B, and undetectable in group C and D. Fas and
      FasL were negative in all groups. (5) No inflammatory cell infiltration was found
      in retina, liver and kidney tissue ninety days after the surgery. CONCLUSIONS:
      Sustained RAPA DDS and eyedrops can prolong allograft survival and inhibit cornea
      neovascularization in rabbit model. However, RAPA DDS is better than eyedrops.

PMID- 16638274
TI  - [Clinical observation of wound dehiscence after penetrating keratoplasty].
AB  - OBJECTIVE: To investigate the treatment of wound dehiscence after penetrating
      keratoplasty and to evaluate the influence of this complication on visual
      outcome. METHODS: A retrospective analysis of 32 patients with wound dehiscence
      that undergone penetrating keratoplasty in Zhongshan Ophthalmic Center from July
      1997 to June 2003 was performed. All involved eyes were undergone wound repair
      with or without iris excision, lensectomy, intraocular lens removal, anterior
      vitrectomy and stage I or stage II pars plana vitrectomy with gas or silicone oil
      tamponade according to variable extents of host-graft wound dehiscence in
      individual patient. Visual outcome, transparency of graft, intraocular pressure
      and structure integrity of ocular posterior segment were followed-up for 6-18
      months in details. These data were used to summarize the specific characteristics
      of this type of ocular trauma. RESULTS: Surgical outcomes were recorded as the
      following: 24 eyeballs were rescued, but eight of them developed phthisis bulbi.
      Broken or loose sutures of eyes were found in eight cases. Six cases achieved
      better visual acuity, all of which maintained clear grafts with normal
      intraocular pressure, and no vitreous hemorrhage or choroidal/retinal detachment
      occurred. In 14 eyes with wound dehiscence of 1/4-1/2 circle, eight cases ended
      with decreased visual acuity, 11 with grafts opacities, five with abnormal
      intraocular pressure (above or below the normal range). In eight eyes with wound
      dehiscence of 1/2-3/4 circle, seven cases got decreased visual acuity, five with
      graft opacities, seven with abnormal intraocular pressure, four with vitreous
      hemorrhage, and four developing choroidal/retinal detachment. In the two eyes
      with wound dehiscence over 3/4 circle, both resulted in graft opacities with no
      light perception. Vitreous hemorrhage, choroidal/retinal detachment as well as
      phthisis bulbi occurred due to low intraocular pressure. CONCLUSIONS: After
      penetrating keratoplasty, the wounds of corneal graft show tectonic instability
      and poor resistance to tension. Traumatic wound dehiscence after penetrating
      keratoplasty often complicate with intraocular content herniation, vitreous
      hemorrhage, and choroidal/retinal detachment. Usually, this kind of trauma is
      from severe injuries and prognosis is worse than the common ocular trauma.

PMID- 16638275
TI  - [In vivo study of normal human limbal and central corneas using laser confocal
      microscope].
AB  - OBJECTIVE: To observe the microstructure and cellular populations of normal human
      limbal and central corneas using laser confocal microscope. METHODS: The study
      was consisted of 28 eyes of 15 examiners (age distribution, 16-61 years). After
      examinations with slit lamp biomicroscopy and ophthalmoscope, the images of
      superior, inferior limbus and central cornea were acquired by laser confocal
      microscope. Corneal microstructure and cell morphology were analyzed, and cell
      densities were measured. RESULTS: Lateral (x, y axis) and axial (z axis) images
      of limbal and central cornea were clear and vivid. Limbal palisades of Vogt were
      visible at the superior and inferior limbus. The red blood cells in the vessel of
      limbus were visible. The arrangement of surface epitheliums was rather loose,
      with bright borders and dark cell bodies. The surface epithelial cell density was
      (812 +/- 297) cells/mm(2) at the superior limbus and (785 +/- 263) cells/mm(2) at
      the inferior limbus. There was no statistical difference between the two group (P
      > 0.05). The bright and dendriform Langerhans cells were readily visible just
      under the epithelial cells. The Langerhans cell density was (288 +/- 102)
      cells/mm(2) at the superior limbus and (254 +/- 127) cells/mm(2) at the inferior
      limbus. There was no statistical difference between the two group (P > 0.05). At
      central cornea, the surface epithelial cells were loose, the borders of the cell
      were clear and bright, and the cell bodies were dark. The cell density was (1098
      +/- 315) cells/mm(2), there were more cells in central cornea than other area of
      superior and inferior limbus (P < 0.05). The arrangement of basal epithelial
      cells was tight. Nerve plexus at subepithelium and anterior stroma were prominent
      with strong brightness. Langerhans cells were occasionally visible, and cell
      density cannot be measured. Subepithelial nerve fibers were thin with high
      tortuosity and a lot of branches, and deeper ones were thick with low tortuosity
      and few branch. In the stroma, separated keratocytes were visible under dark
      background, the boundaries were vague, the nucleis were bright and spindly.
      Hexagonal endothelial cells were arranged in order with light cell bodies and
      dark borders. The thickness of whole cornea, stroma or epithelium was (543.0 +/-
      62.9), (462.0 +/- 69.5), (59.9 +/- 11.2) microm respectively. CONCLUSIONS: Laser
      confocal microscopy provides non-invasive, real-time, in vivo images of limbal
      and central corneas characterized with refined image definition, exact depth
      localization. It is valuable for basic research and clinical diagnosis of corneal
      disease.

PMID- 16638276
TI  - [Management of corneo-conjunctival malignant melanoma with "no touch technique"
      surgical excision and corneoscleral lamellar keratoplasty].
AB  - OBJECTIVE: To study the management of "no touch technique" surgical excision and
      corneoscleral lamellar keratoplasty in the treatment of corneo-conjunctival
      malignant melanoma. METHODS: Surgical excision for corneo-conjunctival malignant
      melanoma in six cases, from October 1989 to January 2004 in Zhongshan Ophthalmic
      Center, were performed. The entire tumors were removed in one piece without
      touching the tumor (no touch technique). The incision was outlined 4-6 mm outside
      the pigmented conjunctival mass, and 2 mm outside the corneal component.
      Dissecting deep enough without any tumor cell left to yield a tumor-free bed.
      After surgical incision, the host eyeball defect was covered with partial or
      total corneoscleral lamellar graft from fresh donor, and the conjunctiva defect
      was covered with or without amniotic membrane transplantation. All the patients
      were followed up to 6 months. RESULTS: The tumors in the remaining conjunctival
      margins were completely removed by local dissection combined with cryotherapy in
      the six cases. Three cases were treated with partial corneoscleral lamellar
      keratoplasty, two cases with total corneoscleral lamellar keratoplasty and one
      case with total corneoscleral lamellar keratoplasty plus amniotic membrane
      transplantation. All cases were subsequently treated with 0.01% thiotepa eyedrops
      and supplemental dacarbazine chemotherapy. At the average 43.5 months follow-up
      time (14.6 years to 6 months), no evidences of local recurrence of malignant
      melanoma or distant metastasis were observed. CONCLUSION: The clinical study
      suggests that using surgical excision of "no touch technique" to remove tumor in
      whole piece with corneoscleral lamellar keratoplasty is effective in the
      treatment of corneo-conjunctival malignant melanoma.

PMID- 16638277
TI  - [The clinical study of endoscopic cyclophotocoagulation on the management of
      refractory glaucoma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of endoscopic
      cyclophotocoagulation (ECP) in the management of refractory glaucoma. METHODS:
      ECP procedures were performed on fifty-one eyes of 47 patients with refractory
      glaucoma by using the Microprobe (Endo Optiks, URAM E2) integrated laser
      endoscope system. All patients were followed-up from 6 to 16 months (mean 10.8
      months), with four eyes receiving a second treatment. The changes of intraocular
      pressure (IOP), visual acuity and complication were pre- and post-operatively
      observed. RESULTS: Compared to preoperation, the IOP of postoperation was
      significantly (P < 0.01) decreased at week 1, 4, 12, and 24 [(35.3 +/- 13.0) mm
      Hg (1 mm Hg = 0.133 kPa) vs (19.9 +/- 13.2) mm Hg, (22.0 +/- 11.6) mm Hg, (17.6
      +/- 11.6) mm Hg, and (17.0 +/- 10.4) mm Hg, x +/- s, respectively]. The mean
      number of IOP-decreased drugs used was significantly (P < 0.01) reduced from 3.3
      to 1.0 of postoperation. 51.0% of all 51 eyes with the postoperative IOP less
      than 21 mm Hg did not receive any drug, and 25.5% with supplemental drug
      treatment. The visual acuity was significantly (P < 0.01) improved
      postoperatively. Postoperative hyphema were found in 4 eyes, fibrous exudates in
      23 eyes, and exudative choroids detachment in 2 eyes, all of which occurred at
      the early postoperative stage and were healed within 2-16 days. No other
      complications were observed. CONCLUSION: ECP is a safe and effective procedure
      for the management of refractory glaucoma without serious complications.

PMID- 16638278
TI  - [Analysis of changes of anterior chamber depth after IOL implantation].
AB  - OBJECTIVE: To evaluate the changes of the anterior chamber depth (ACD) and the
      related factors after cataract surgery with IOL implantation in order to achieve
      the intended postoperative refraction. METHODS: Preoperative and postoperative
      ACD were examined in 117 patients (177 eyes) who underwent cataract surgery
      (phacoemulsification and posterior chamber IOL implantation). Correlations
      between changes of ACD and the axial lengths of the eyes, K-readings and IOL A
      constants were assessed. Patients were followed-up for 3 to 24 months. RESULTS:
      (1) There was significant difference between preoperative ACD (3.19 +/- 0.39) mm
      and postoperative ACD (4.22 +/- 0.65) mm (P = 0.000). (2) The mean postoperative
      ACD change was (1.03 +/- 0.61) mm. The correlations between the ACD changes and
      the axial lengths of the eye and K-readings were statistically significant. (r =
      0.866, r = 0.946, P = 0.001). (3) There was significant difference between
      preoperative ACD and postoperative ACD in the three different A-constants groups
      (118.9, 118.0 and 118.4) (P = 0.004, 0.001 and 0.001). There was significant
      difference between ACD changes in patients with A-constant 118.9 and that of
      118.0 or 118.4 (P = 0.007, P = 0.01). There was no significant difference between
      ACD changes in patients with A-constant 118.0 and that of 118.4 (P = 0.957).
      CONCLUSION: Cataract surgery deepened anterior chambers at varying degrees,
      depending on the axial lengths of the eye, K-readings and the IOL A-constants.
      ACD changes and relevant factors should be considered in studying the accuracy of
      IOL refraction formula and in adjusting the calculated data.

PMID- 16638279
TI  - [Efficacy of 5-fluorouracil polyactic acid microsphere in prevention of
      proliferative vitreoretinopathy].
AB  - OBJECTIVE: To evaluate the efficacy of 5-fluorouracil polyactic acid microsphere
      in prevention of proliferative vitreoretinopathy (PVR). METHODS: 5-fluorouracil
      polyactic acid microsphere or 5-fluorouracil were used to implant into rabbits
      vitreous cavity. 48 healthy rabbits were divided into 3 groups: rabbits in Group
      1 received implantation of 5-fluorouracil polyactic acid microsphere; rabbits
      Group 2 served as polyactic acid microsphere control; rabbits in Group 3 received
      only 5-fluorouracil powder. Macrophages were injected into vitreous cavity of
      rabbit to induce PVR. 0.2 ml BSS containing 25 mg microsphere with 2.6 mg 5
      fluorouracil was injected into vitreous cavity of two eyes in Group 1. 0.2 ml BSS
      containing 25 mg microsphere without medicine and 0.2 ml BSS containing 2.6 mg 5
      fluorouracil were injected into rabbits vitreous cavity in Group 2 and 3
      respectively, Drug content in aqueous humor was measured regularly. Release
      feature of 5-fluorouracil polyactic acid microsphere in vivo was observed. The
      efficacy of the inhibition of PVR was evaluated according to Ryan's grade of
      proliferative vitreoretinopathy. RESULTS: The releasing time of 5-fluorouracil
      polyactic acid microsphere was much longer than 5-fluorouracil powder. Its half
      life T(1/2) was 379.05 h with low clearance rate. The attack rate of retinal
      detachment in Group 2 was 62.5% and 71.9% on the 21st and 28th day respectively.
      The attack rate of retinal detachment in Group 3 was 64.3% and 78.6% whereas that
      of Group 1 was 13.3% and 13.3% on the 21st and 28th day. There was statistical
      difference in retinal detachment rate in Group 1 and 2 or 3 (P < 0.01). No
      differences was found in retinal detachment ration in Group 2 and 3 (P > 0.05).
      CONCLUSION: Implantation of 5-fluorouracil polyactic acid microsphere into
      vitreous cavity can effectively prevent proliferative vitreoretinopathy induced
      by macrophages in rabbit model.

PMID- 16638280
TI  - [Effect of pirenzepine on form deprivation myopia in chicks and its possible
      mechanism].
AB  - OBJECTIVE: To observe the effect of M1-selective muscarinic antagonist,
      pirenzepine, on form deprivation myopia and investigate the expression of MMP-2
      and its inhibitor TIMP-2 in the fibrous sclera in order to better understand the
      mechanism by which pirenzepine inhibits myopia. METHODS: 40 chicks after birth
      one day were divided into 4 groups randomly: I. Control group; II. Form
      deprivation group; III. Vehicle application group; IV. Pirenzepine injected
      group. Form deprivation myopia was established in right eyes of group II, III, IV
      by placement of a translucent occluder. The deprived eyes of group III and IV
      received daily subconjunctival administration of vehicle PBS and pirenzepine
      respectively. Optical measures such as refraction, axial length, equatorial
      diameter were made at the end of the experiment. Total RNA and protein were
      extracted from the posterior fibrous sclera chicks. The expression of MMP-2 and
      TIMP-2 mRNA and protein were investigated with RT-PCR and Western blot analysis
      respectively. RESULTS: Refraction status, axial length, equatorial diameter of
      the eyes in pirenzepine injected group were significantly lower when compared
      with form deprivation group (P < 0.01), but the parameters were higher when
      compared with normal control group therefore relatively myopic changes were
      detected. There were no significant difference between drug control and
      pirenzepine injected group when optical measures and the expression of MMP-2,
      TIMP-2 were concerned (P > 0.05). The expressions (mRNA and protein) of both MMP
      2 and TIMP-2 were significantly different in form deprivation group when compared
      with normal control group (MMP-2 mRNA increased by 143.51%, P < 0.01; protein
      increased by 114.60%, P < 0.01; TIMP-2 mRNA decreased by 55.05%, P < 0.01;
      protein decreased by 53.73%, P < 0.01). In pirenzepine injected group the
      relative expression of MMP-2 mRNA and protein were decreased obviously by 41.95%
      (P < 0.01) and by 36.16% (P < 0.01), while TIMP-2 mRNA and protein expression was
      increased significantly by 72.46% (P < 0.01) and by 53.05% (P < 0.01)
      respectively compared with the form deprived group. CONCLUSION: Subconjunctivally
      administration of the M1 selective muscarinic antagonist, pirenzepine, partly
      prevents or restrains form deprivation induced myopia. It may exert its
      inhibitory effect by modulating the expression of MMP-2 and TIMP-2 in fibrous
      sclera.

PMID- 16638281
TI  - [Tissue culture of bovine lens as an in vitro model for posterior capsule
      opacification and the effects of pranoprofen on the cell confluence].
AB  - OBJECTIVE: To establish an in vitro model of posterior capsule opacification
      (PCO) by culturing the posterior capsule of bovine lens, to observe the
      proliferation and differentiation of lens epithelial cells and to study the
      influence of serum and pranoprofen eyedrops on cell confluence of this model.
      METHODS: The bovine lens posterior capsule was spread on the surface of a 25 ml
      culture flask with cell layer upward. DMEM with 0%, 10% and 20% fetal calf serum
      was used as culture medium. The cell coverage and confluence time on the
      posterior capsule were observed by inverted microscope and the cell morphology
      was observed by Giemsa staining and scanning electron-microscope. Pranoprofen was
      added to the culture medium at a concentration similar to the aqueous humor
      concentration (0.23 mg/L), which was presented at 4 hours after the instillation
      of pranoprofen eyedrops. The difference of confluence time between the treated
      group and the control group was compared. RESULTS: The lens epithelial cells
      migrated and proliferated rapidly on the posterior capsule from the equatorial
      region to the center. The cell coverage was increased and the confluence time was
      shortened with the increase of serum concentration (P < 0.05). The PCO and
      wrinkles were presented. Pranoprofen at 0.23 mg/L could inhibit the confluence of
      lens epithelial cells (P < 0.01). CONCLUSIONS: The in vitro model for PCO was an
      useful method to study the mechanism of PCO formation. Pranoprofen can inhibit
      the proliferation of lens epithelial cells and is a safe and efficient drug for
      preventing the occurrence of PCO and can be used as a routine medication after
      the cataract operation.

PMID- 16638286
TI  - [Pathogenic free-living amoebic keratitis in China].
AB  - The first case of acanthamoebic keratitis in China was reported by JIN Xiu-ying
      et al in 1992. Over past ten years, extensive researches on this vision
      threatening keratitis in the etiology, biology, specimen culture and preservation
      of pathogen, pathogenesis and virulence, animal model, pathology and immunology,
      clinical diagnosis and management have been carried out.

PMID- 16638291
TI  - [To have a full realization of the importance of clinical epidemiological
      investigation].

PMID- 16638292
TI  - [A multicentre study on the pathogenic agents in 665 adult patients with
      community-acquired pneumonia in cities of China].
AB  - OBJECTIVE: To investigate the pathogenic causes of community-acquired pneumonia
      (CAP) in adult patients in China, the relation of previous antibiotic use and the
      Pneumonia Patient Outcome Research Team (PORT) classification to microbial
      etiology, and the prevalence of drug resistance of common CAP bacteria. METHODS:
      A prospective study was performed on 665 consecutive adult patients with CAP at
      12 centers in 7 Chinese cities during one year. The etiology of pneumonia was
      considered if one of the following criteria was met: (1) valid sputum sample
      yielding one or more predominant strains; (2) blood cultures yielding a bacterial
      pathogen; (3) seroconversion, a > or = 4-fold increase or decrease titers of
      antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella
      pneumophila. Minimum inhibitory concentration (MIC) of respiratory tract isolates
      was determined using the agar dilution method. RESULTS: Pathogens were identified
      in 324/610 patients (53.1%) with valid serum samples and sputum cultures as
      follows: Mycoplasma pneumoniae (126, 20.7%), Streptococcus pneumoniae (63,
      10.3%), Haemophilus influenzae (56, 9.2%), Chlamydia pneumoniae (40, 6.6%),
      Klebsiella pneumoniae (37, 6.1%), Legionella pneumophila (31, 5.1%),
      Staphylococcus aureus (23, 3.8%), Escherichia coli (10, 1.6%), Moraxella
      catarrhalis (8, 1.3%), Pseudomonas aeruginosa (6, 1.0%). Of 195 patients with a
      bacterial pathogen, an atypical pathogen was identified in 62 (10.2%) cases. The
      non-susceptibility rate of Streptococcus pneumoniae to penicillin, azithromycin,
      and moxifloxacin was 20.3%, 75.4% and 4.3% respectively. CONCLUSIONS: Atypical
      pathogens have important role in CAP, with Mycoplasma pneumoniae being the most
      common pathogen, and mixed infection of atypical pathogens with bacteria was
      found in 10.2% of the cases. Streptococcus pneumoniae and Haemophilus influenzae
      remain the most important bacteria for CAP. More than 75.0% of Streptococcus
      pneumoniae was resistant to macrolides and 20.3% was resistant to penicillin.

PMID- 16638293
TI  - [A retrospective study of one case of human infection by the highly pathogenic
      avian influenza A (H5N1)].
AB  - OBJECTIVE: To describe the clinical features of the infection caused by the
      highly pathogenic avian influenza A (H(5)N(1)). METHODS: A previously healthy 24
      year old woman presented to our hospital on November 7, 2005. She was confirmed
      to be an H(5)N(1) infected case after death. The clinical, radiological and
      epidemiological data were analyzed. RESULTS: The patient had a history of direct
      contact with diseased and dead poultry (chicken and duck). The disease course was
      10 days from onset of illness to death, and fever preceded dyspnea by 5 days. On
      admission, the striking characteristics were acute community-acquired pneumonia
      (CAP) and acute respiratory distress syndrome (ARDS), and the major radiographic
      abnormalities included extensive infiltration bilaterally, focal consolidation
      and air bronchograms. The radiographic and clinical deterioration was rapid, and
      the patient died in less than 3 days after hospitalization. The diagnosis of
      influenza A (H(5)N(1)) was confirmed by means of reverse transcriptase-polymerase
      chain reaction (RT-PCR) and real-time PCR on specimens of the lower respiratory
      tract, performed by Chinese Center for Disease Control. The postmortem
      examination showed bronchial hyperemia, extensive consolidation, serous cavity
      effusions, disseminated intravascular coagulation (DIC) and multiple organ
      failure (MOF). CONCLUSIONS: Human infection by the highly pathogenic avian
      influenza A (H(5)N(1)) is a fatal communicable disease. Information of avian
      influenza A (H(5)N(1)) virus, more attention to the epidemiologic data, and early
      intervention are critical in reducing the mortality.

PMID- 16638294
TI  - [Application of pulmonary infection control window as switching point for
      sequential invasive to noninvasive ventilation in treatment of severe respiratory
      failure of chronic obstructive pulmonary disease: a randomized controlled study].
AB  - OBJECTIVE: To evaluate the feasibility and the efficacy of early extubation and
      sequential noninvasive mechanical ventilation (MV) switched by pulmonary
      infection control window (PIC window) in chronic obstructive pulmonary disease
      (COPD) with exacerbated hypercapnic respiratory failure. METHODS: Respiratory or
      Medical Intensive Care Units (RICU/MICU) of 12 teaching hospitals in China
      participated in this study. COPD patients with severe hypercapnic respiratory
      failure exacerbated by pulmonary infection, and for whom intubation and MV were
      indicated, were enrolled in the study. PIC window was defined as the time point
      when pulmonary infection was considered under control based on clinical
      parameters. At PIC window, all the cases were randomly assigned to sequential MV
      group or conventional MV group. The invasive MV duration, ventilator-associated
      pneumonia (VAP), days in ICU and mortality rate in both groups were measured.
      RESULTS: Ninety cases were enrolled. Compared with conventional MV group (n = 43)
      sequential MV group (n = 47) had shorter duration of invasive MV [(6.4 +/- 4.4),
      (11.3 +/- 6.2) d, P = 0.000], lower rate of VAP (3/47, 12/43, P = 0.014), fewer
      days in ICU [(12 +/- 8), (16 +/- 11) d, P = 0.047] and lower mortality rate
      (1/47, 7/43, P = 0.025). CONCLUSION: Early extubation followed by non-invasive MV
      initiated at the point of PIC window may decrease the duration of invasive MV and
      improve the prognosis.

PMID- 16638295
TI  - [The effect of subglottic secretion drainage on prevention of ventilator
      associated lower airway infection].
AB  - OBJECTIVE: To assess the influence of subglottic secretion drainage (SSD) on the
      morbidity of ventilator-associated pneumonia (VAP) in mechanically ventilated
      patients. METHODS: All studied patients who received mechanical ventilation (MV)
      estimated for more than 48 hours were intubated with a special type endotracheal
      tube with a small-bore cannula in the wall for SSD. The patients were randomly
      divided into two groups receiving SSD (group A) and usual care (non-SSD, group B)
      respectively. Bacterial culture of samples from lower airway secretion taken
      regularly by Bagpipe Protected specimen brush were performed, and at the same
      time the subglottic secretion and scraping-pharynx specimen were collected for
      bacterial quantitative culture and antibiotic sensitivity test. The clinical data
      were recorded and the duration of MV, the length of stay in hospital and the time
      of occurrence of ventilator-associated airway infection (VAAI) and VAP were
      analyzed. RESULTS: (1) In patients with MV < 5 days: The incidence of VAAI and
      VAP in group A (VAAI: 8.3% and VAP: 6.0%) was lower than those in group B (VAAI:
      24.0% and VAP: 20.0%, P < 0.05). The onset of VAAI and VAP was delayed in group A
      [VAAI: (7.4 +/- 3.0) d and VAP: (7.7 +/- 3.2) d] as compared with group B [VAAI:
      (4.9 +/- 1.4) d and VAP: (4.6 +/- 2.1) d, P < 0.05]. There were no significantly
      statistic differences for hospital mortality, overall duration of mechanical
      ventilation, lengths of stay in the hospital between the two groups (P > 0.05).
      (2) The same organism as that previously found from subglottic secretion was
      isolated by PSB in 21.4% patients. (3) The concentration of bacteria in
      subglottic secretion from group A was decreased significantly as compared to that
      of group B. (4) Gram-negative bacilli were the main pathogens in the lower
      respiratory tract in the two groups. The dominant bacteria cultured in the lower
      airway secretions were Pseudomonas aeruginosa and Acinetobacter baumanii. There
      was no significant difference between the two groups in the spectrum of bacteria
      (P > 0.05). CONCLUSIONS: (1) SSD reduced the incidence of VAAI and VAP in
      patients with MV < 5 d. The onset of VAAI and VAP was delayed in group A as
      compared with group B. The concentration of bacteria in the subglottic secretion
      was significantly reduced by subglottic secretion drainage. (2) Migration of the
      dominant bacteria of the subglottic secretion was one of the important factors
      for VALAI. (3) The dominant cultured bacteria in the lower airway secretion were
      gram-negative bacilli, most commonly Pseudomonas aeruginosa and Acinetobacter
      baumanii.

PMID- 16638296
TI  - [Clinical analysis of bronchopulmonary infection with hypermastigotes: a report
      of two cases and review of the Chinese literature].
AB  - OBJECTIVE: To describe the clinical features of bronchopulmonary infection with
      hypermastigotes. METHODS: Two cases of bronchopulmonary infection with
      hypermastigotes were reported. The clinical features of another six cases from
      the Chinese literature were reviewed. RESULTS: Bronchopulmonary infection with
      hypermastigotes mostly occurs in the hot and humid southern area. The symptoms
      are severe, with different manifestations such as chronic cough, asthma,
      pneumonia, and even lung abscess. Final diagnosis is made by the presence of
      hypermastigotes in smears of secretions from the respiratory tract. An
      antiprotozoal such as metronidazole is always effective. CONCLUSION: In patients
      with unexplained cough, asthma, and pneumonia or lung abscess which do not
      respond to ordinary therapy, rare pathogens such as hypermastigotes need to be
      considered.

PMID- 16638297
TI  - [Effects of all-trans retinoic acid on phenotype switch and migration of human
      pulmonary artery smooth muscle cells in vitro and the possible mechanisms].
AB  - OBJECTIVE: To investigate the effects of all-trans retinoic acid (atRA) on
      phenotype switch and migration of human pulmonary artery smooth muscle cells
      (PASMC) in vitro and the possible mechanisms. METHODS: Cultured human PASMC were
      divided into 8 groups randomly: group A (control group), group B (vehicle group),
      group C (treated with 10% fetal cattle serum), group D, group E, group F, group
      G, and group H (treated with atRA at the concentrations of 0.001 micromol/L, 0.01
      micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L respectively as well as
      10% fetal cattle serum). Then, expression of JWA mRNA in human PASMC was detected
      by reverse transcriptase-polymerase chain reaction (RT-PCR), cell migration was
      measured using modified Boyden's chamber, and expression of SM-alpha-actin mRNA
      and protein was detected by RT-PCR and immunohistochemistry respectively. The
      difference between the groups was analyzed. RESULTS: There was no significant
      difference in the JWA mRNA expression of human PASMC between group A (0.125 +/-
      0.014), group B (0.164 +/- 0.018) and group C (0.164 +/- 0.006), but the JWA mRNA
      expression in group D (0.326 +/- 0.018), group E (0.440 +/- 0.033), group F
      (0.460 +/- 0.040), group G (0.589 +/- 0.024) and group H (0.821 +/- 0.050) were
      significantly higher than those of group A, group B and group C (all P < 0.01).
      The number of migrating cells in group C (30.4 +/- 7.4) was higher than those in
      group A (7.2 +/- 1.9) and group B (6.8 +/- 2.3, all P < 0.01), but the number of
      migrating cells in group D (21.8 +/- 2.9), group E (17.2 +/- 2.3), group F (14.4
      +/- 3.5), group G (12.6 +/- 3.4) and group H (8.8 +/- 2.4) was significantly
      lower than that in group C (all P < 0.01), and there was no significant
      difference between group G, group H and group A, group B. The SM-alpha-actin
      protein expression in group C (0.219 +/- 0.018) was significantly lower than
      those in group A (0.319 +/- 0.011) and group B (0.325 +/- 0.005, all P < 0.01),
      but the protein expression in group E (0.328 +/- 0.016), group F (0.386 +/-
      0.025), group G (0.442 +/- 0.017) and group H (0.501 +/- 0.018) was significantly
      higher than that in group C (all P < 0.01), while that in group F, group G and
      group H was significantly higher than those in group A and group B (all P <
      0.01). The SM-alpha-actin mRNA expression in group C (0.144 +/- 0.009) was
      significantly lower than those in group A (0.299 +/- 0.023) and group B (0.296 +/
      0.041, all P < 0.01), but the mRNA expression in group D (0.487 +/- 0.014),
      group E (0.501 +/- 0.020), group F (0.611 +/- 0.018), group G (0.774 +/- 0.013)
      and group H (0.851 +/- 0.026) was significantly higher than those in group A,
      group B and group C (all P < 0.01). CONCLUSION: atRA increased JWA gene
      expression in human pulmonary artery smooth muscle cells, and meanwhile, the
      cells differentiated into a contractive phenotype and the cell migration
      decreased.

PMID- 16638298
TI  - [Application of serum surface-enhanced laser desorption/ionization proteomic
      patterns in distinguishing non-small cell lung cancer patients from healthy
      people].
AB  - OBJECTIVE: To explore the application of serum surface-enhanced laser
      desorption/ionization (SELDI) marker patterns in distinguishing non-small cell
      lung cancer patients from healthy people by protein chip technology. METHODS: One
      hundred and sixty-three serum samples (123 patients with lung cancer and 40
      healthy persons), were randomly divided into a training set [94 cases, 53 non
      small cell lung cancer (NSCLC), 21 small cell lung cancer and 20 healthy persons]
      and a blinded test set (69 cases), were included for analysis by surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Five
      protein peaks at 11,493, 6,429, 8,245, 5,336 and 2,536 were automatically chosen
      for the system training and the development of a decision classification tree
      model (marker pattern). The accuracy of the model was tested with the blinded
      test set (an independent set of masked serum samples from 49 patients with NSCLC
      and 20 healthy persons). RESULTS: The model differentiated the patients with
      NSCLC from the healthy people with a sensitivity of 95.9% (71/74) and a
      specificity of 90.0% (18/20) in the training set and a sensitivity of 83.7%, and
      a specificity of 80.0% in the blinded set respectively. CONCLUSION: SELDI-TOF-MS
      technique can correctly distinguish NSCLC patients from healthy people, and it
      has the potential for the development of a screening test for the detection of
      NSCLC.

PMID- 16638299
TI  - [The effect of siRNA-Her2/neu on the drug sensitivity of Her2/neu-overexpressing
      lung adenocarcinoma cell line].
AB  - OBJECTIVE: To explore the effect of synthesized siRNA targeting Her2/neu oncogene
      on the drug sensitivity of Her2/neu-overexpressing lung adenocarcinoma cell line.
      METHODS: The experiments consisted of four groups including an untreated control
      group, an empty vector group, an unrelated siRNA group, and a Her2/neu siRNA
      group. Every experiment was repeated five times. Lung adenocarcinoma cell line
      Calu-3 was transfected with siRNAs formulated LipofectAMINE 2000, and Her2/neu
      protein and P-gp of each group were determined by flow cytometry (FCM). The
      chemosensitivity of transfected cells to cisplatin (DDP) was measured by MTT.
      Cell apoptosis detection kit (Annexin V method) was used to examine the drug
      induced apoptosis rate. RESULTS: The Her2/neu protein and P-gp positive
      expression rate in the Her2/neu siRNA group, the untreated control group, the
      empty vector group and the unrelated siRNA group were [(25.04 +/- 1.56)%, (4.24
      +/- 1.01)%], [(98.24 +/- 2.23)%, (5.11 +/- 2.98)%], [(95.67 +/- 1.98)%, (6.98 +/-
      2.47)%] or [(94.79 +/- 0.87)%, (5.59 +/- 3.66)%], respectively. Introduction of
      the sequence specific siRNA into Her2/neu positive Calu-3 cells in vitro greatly
      reduced the cell surface expression of the Her2/neu protein, but had no effect on
      P-gp level. Consequently the inhibitory rate of DDP in combination with siRNA
      targeting Her2/neu was (67.1 +/- 2.3)%, but it was (48.1 +/- 3.5)%, (46.3 +/-
      5.9)% and (50.2 +/- 2.9)% in the untreated control, the empty vector and the
      unrelated siRNA groups, respectively. There was a significant difference between
      Her2/neu siRNA group and other three groups (P < 0.01). The FCM results showed
      the apoptosis rate of DDP combined with siRNA-Her2/neu was elevated as compared
      with the unrelated siRNA group, the empty vector group or the untreated control
      group. CONCLUSION: Sequence specific siRNA-Her2/neu was capable of enhancing the
      chemosensitivity of Calu-3 cells to cisplatin.

PMID- 16638300
TI  - [Effect of anti-vascular endothelial growth factor antibody on pleurodesis
      induced by transforming growth factor-beta or doxycycline in rabbits].
AB  - OBJECTIVE: The intrapleural injection of transforming growth factor-beta (TGF
      beta) or doxycycline produces excellent pleurodesis in rabbit models. However,
      the intrapleural injection of these agents induces large pleural effusion which
      is possibly related to vascular endothelial growth factor (VEGF). This study
      investigated whether anti-VEGF antibody has any effect on the fluid production or
      the pleurodesis induced by TGF-beta or doxycycline in rabbits. METHODS: Two
      groups of New Zealand white rabbits (7 each) were given TGF-beta 5.0 microg
      intrapleurally. The TGF-beta treatment group received anti-VEGF antibody 10 mg/kg
      intravenously 24 h before TGF-beta injection and the TGF-beta control group
      received no antibody. Another two groups of New Zealand white rabbits (7 each)
      were given doxycycline 10 mg/kg intrapleurally after chest tube placement. The
      doxycycline treatment group received 10 mg/kg anti-VEGF antibody intravenously 24
      h before doxycycline injection and the doxycycline control group received no Anti
      VEGF antibody. The rabbits were sacrificed at 2 weeks and the pleurodesis score
      was graded macroscopically on a 1-8 scale. The degree of angiogenesis in pleural
      tissues was assessed by immunohistochemical staining for factor VIII which was
      assessed by computer-assisted digital analysis. RESULTS: The administration of
      anti-VEGF antibodies had no effect on pleural fluid volume or the characteristics
      of the fluid. The mean pleurodesis score of TGF-beta control group (7.7 +/- 0.8)
      was significantly (P < 0.05) higher than that of the antibody pre-treatment TGF
      beta group (4.4 +/- 2.4). The mean pleurodesis score of the doxycycline control
      group (6.0 +/- 1.7) was significantly (P < 0.05) higher than that of the antibody
      pre-treatment doxycycline group (2.0 +/- 0.9). The administration of the anti
      VEGF antibody also reduced the angiogenesis. The percentage of pleural tissue
      demonstrating angiogenesis in the TGF-beta control group (4.9 +/- 0.4)% was
      significantly (P < 0.05) higher than that of the antibody treatment TGF-beta
      group (2.9 +/- 0.7)%. The percentage of pleural angiogenesis in the doxycycline
      control group (6.9 +/- 2.2)% was significantly (P < 0.05) higher than the
      antibody pre-treatment doxycycline group (2.2 +/- 0.9)%. CONCLUSIONS: Anti-VEGF
      antibody significantly inhibits the pleurodesis induced by doxycycline or TGF
      beta. This observation suggests that VEGF and angiogenesis play a pivotal role in
      the production of pleurodesis.

PMID- 16638301
TI  - [Effects of sense vascular endothelial growth factor cDNA transfection on
      mononuclear chemotaxis protein-1 expression in rat pulmonary microvessel
      endothelial cells].
AB  - OBJECTIVE: To study the transformation characteristics of tight junction of
      microvessel endothelial cells in bleomycin (BLM) induced pulmonary fibrosis (PF),
      and the effects of vascular endothelial growth factor (VEGF) on mononuclear
      chemotaxis protein-1 (MCP-1) mRNA expression in pulmonary microvessel endothelial
      cells (EC). METHODS: Forty healthy rats were equally divided into a control and
      an experimental group in random. In the experimental group, PF were induced by
      BLM application. In each group, 10 rats were instilled by lanthanum sal at 3, 7,
      14 and 28 d after BLM application, and lung samples were made and observed by
      transmission electron microscopy. The pulmonary microvessel EC of the other 10
      rats in each group were preserved by tissue culture methods at the same time, and
      the cells were transfected with sense VEGF cDNA, and then MCP-1 mRNA expression
      was detected by reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique. RESULTS: Blood vessel endothelial cells of the control group were
      intact. The basement membrane was shown as a continuous line. Granules of
      lanthanum sal did not cross the tight junction of endothelial cells. The width of
      the junction gap in rats of the experimental group treated at different times was
      increased and lanthanum particles of high density were seen in the gap junction,
      particularly on day 3, and were distributed in the area of subendothelium. The
      MCP-1 mRNA expression in VEGF transfected microvessel EC was significantly higher
      than that of the control group (1.21 +/- 0.22 vs 0.36 +/- 0.06, P < 0.05).
      CONCLUSION: In BLM induced PF, the opening of the tight junction of EC, and the
      high expression of MCP-1 induce inflammatory cell infiltration and cytokine over
      secretion, which in turn enhances proliferation of fibroblasts, one of the
      important factors underlying lung fibrosis.

PMID- 16638302
TI  - [The epidemiology and management of influenza].

PMID- 16638315
TI  - [Current status and problems of endovascular treatment for ischemic
      cerebrovascular diseases in China].

PMID- 16638317
TI  - [Endovascular stent implantation in treatment of intracranial wide-necked
      aneurysms].
AB  - OBJECTIVE: To evaluate the effectiveness and feasibility of treatment of
      intracranial wide-necked aneurysms with a new technique of Neuroform self
      expanding stent combined with detachable coil. METHODS: A retrospective analysis
      of thirty patients with intracranial wide-necked aneurysms, 14 males and 16
      females, aged 48 (18-68), wide-necked aneurysms, underwent occlusion of aneurysms
      using Neuroform self-expanding stent combined with detachable coil. RESULTS: 21
      of the 30 aneurysms were completely occluded (70%) and 9 of the 30 aneurysms were
      incompletely occluded (30%) after initial coils embolization. Thromboembolic
      events were found in one case and migration of stent in two cases. Clinical
      follow-up performed in 29 patients showed that only one patient had permanent
      mild hemi-paralysis. Twenty-one patients were followed up for 6-12 months, 7 of
      which needed second treatment and 4 of which showed complete occlusion.
      CONCLUSION: A flexible device, Neuroform self-expanding stent can be safely
      maneuvered through tortuous intracranial vessels, enabling the endovascular
      treatment of complex wide-necked aneurysms. The new technique of Neuroform stent
      combined with detachable coil increases the early outcome of intracranial wide
      necked aneurysm.

PMID- 16638318
TI  - [Copolymer of 2-hydroxyethyl methacrylate for cerebral arteriovenous
      malformation: an experimental study].
AB  - OBJECTIVE: To investigate the feasibility of using methyl methacrylate (MMA) and
      2-hydroxyethyl methacrylate (HEMA) to embolize cerebral arteriovenous
      malformations (AVM). METHODS: Methyl methacrylate (MMA) and 2-hydroxyethyl
      methacrylate (HEMA) in the ratio of 9:1 were solved in 16% alcohol so as to make
      a kind of copolymer (CoHEMA). 12 g glass beads 2 mm in diameter were put into a
      container so as to construct an in vitro model of AVM. The container was
      connected with a normal saline bottle via microcatheter. CoHEMA, as embolized,
      was injected through the microcatheter and the diffusion of CoHEMA was observed
      till the water flow was stopped. CoHEMA was injected through microcatheter into
      the pharyngeal ascending arteries near the rete mirabile (RMB) tissue, similar to
      the human AVM, under digital subtraction angiography until satisfactory
      embolization was obtained, totally 9 RMB tissues in 7 pigs. Five pigs were
      injected with normal saline as controls. The pigs were killed 2 days, 2 weeks,
      and 6 months after embolization respectively and the bilateral RMB tissues were
      taken out to undergo pathological examination. RESULTS: Nine AVM models in vitro
      were constructed with the copolymer dispersed symmetrically among the glass beads
      and stopped the fluid across the model effectively. No copolymer adhered to the
      wall of microcatheter. Nine RMB tissues of 6 pigs were embolized by using CoHEMA.
      Six of the seven pigs survived the procedure except one died of too fast
      injection of copolymer in the primary stage. Follow-up angiography was performed
      in four pigs and found that no recanalization occurred and the copolymer was
      diffused in the vessels 80-150 microm in diameter. In the specimens obtained 2
      days after embolization, neutrophilic granulocytes scattered surrounding the
      copolymer, suggesting minor inflammatory reaction. In the specimens obtained 2
      weeks after embolization no vessel wall damage and morphological change were
      found except minor inflammatory reaction inside the vessels and surrounding
      tissues. In the specimens obtained 2 to 6 months after embolization hyperplasia
      of connective tissue, minor or mediate chronic inflammatory reaction, and giant
      cell reaction inside the vessels and surrounding tissues. CONCLUSION: With low
      viscosity, better biocompatibility, and embolic instability, and easy to be
      injected through delivery microcatheter, CoHEMA is an excellent non-adhesive
      embolic material and can be used in embolic treatment of cerebral AVM.

PMID- 16638319
TI  - [Treatment of dural arteriovenous fistula by transarterial embolization with low
      dose of N-butyl-2-cyanoacrylate].
AB  - OBJECTIVE: To evaluate the efficacy of treatment of dural arteriovenous fistula
      (DAVF) by transarterial embolization with low dose of N-butyl-2-cyanoacrylate
      (NBCA). METHODS: Eighteen patients, 6 males and 12 females, aged 47.5 (23-72),
      with DAVF, 12 with carotid cavernous fistula and 6 with fistula in parietal lobe,
      underwent transarterial embolization with low dose of NBCA (10%-20%). The key
      point of transarterial embolization with low dose of NBCA was that low dose NBCA
      was injected and embolized the veins and then was reversed into the other
      supplying arteries. RESULTS: Seventeen patients with DAVF in cavernous region and
      6 patients with DAVF in parietal lobe were cured anatomically, with the clinical
      syndromes disappearing. In 1 patient with DAVF in cavernous region the clinical
      syndrome were moderately improved after transarterial embolization, however,
      worsened 2 days later. Cerebrovascular angiography demonstrated that the vein was
      not completely embolized and the draining vein was broadened, and the clinical
      syndromes were moderately improved again after carotid artery compression therapy
      for 10 days. CONCLUSION: Convenient and fast, and with low cost and satisfying
      efficacy, transarterial embolization with low dose of NBCA is a better choice for
      treatment of DAVF in some cases. The key point of this approach is that the tip
      of microcatheter is close as much as possible to the fistulae, and NBCA is
      injected into the fistulae and make the vein diffused well. Attention should be
      paid to avoid dangerous anastomosis.

PMID- 16638320
TI  - [Survival prediction for terminal gynecologic cancer patients].
AB  - OBJECTIVE: To construct a scoring system of predicting the survival time of
      terminal gynecologic cancer patients. METHODS: The clinical data of 91 patients
      with terminal gynecologic cancers, aged 56 (13-83), who were not suitable to
      specific anti-cancer therapy and died in the hospital with a mean survival time
      of 27 days (1-240 days) were analyzed retrospectively. Initially univariate
      analysis was performed to evaluate the relationship between 19 clinico
      biochemical indices and survival time. Multiple logistic regression was used to
      analyze 9 out of the 19 clinico-biochemical indices which had significant effects
      on the survival time, and a regression model with 5 indices was constructed by
      backward selection procedure. The regression coefficient of any category was
      divided by the maximum regression coefficient so as to get the score of this
      category. The cores were added together so as to get the overall score of an
      individual patient. RESULTS: Univariate analysis identified 9 factors
      independently and significantly influencing the survival time: short breath,
      Karnofsky performance status (KPS), age, high fever, speed of tumor growth,
      presence or absence of treatment-related complication, blood urea nitrogen (BUN),
      creatinine, and platelet. A regression equation was composed of 5 factors: short
      breath, KPS, age, higher fever, and BUN by multiple logistic regression with a
      correct classification ability of 83.5%. The 91 patients were then divided into 2
      groups based on this prognostic score system: Group A (n = 37) with a score < or
      = 9.5 and the mean survival time of (65 +/- 7) days, and Group B (n = 54) with a
      score > or = 10 and the mean survival time of (19 +/- 2) days. 31 of the 37
      patients in Group A survived > or = 30 days, and 46 of the 54 patients in Group B
      died within 29 days. The Kaplan-Meier survival curves of these 2 group were
      significantly different (P < 0.001). CONCLUSION: A simple, valid, and useful
      prognostic score system has been established.

PMID- 16638321
TI  - [Effect of carbon dioxide pneumoperitoneum during laparoscopic surgery on
      morphology of peritoneum].
AB  - OBJECTIVE: To investigate the influence of carbon dioxide (CO2) pneumoperitoneum
      during laparoscopic surgery on morphology of peritoneum. METHODS: Forty patients
      with myoma of uterus or simple ovarian cyst excluding peritonitis were randomly
      divided into 2 equal groups to undergo laparoscopic surgery with CO2
      pneumoperitoneum or laparotomy respectively. Specimens of parietal peritoneum
      were obtained at different time points, 0, 30, 90, and 120 min after the
      beginning of observation, i.e. e, insufflation or opening of the peritoneal
      cavity, to undergo transmission electron microscopy and scanning electron
      microscopy to observe the morphological changes of mesothelial cells. RESULTS: In
      the laparotomy group, up to the time point of 60 min, there was no marked change
      of mesothelial cells. Intercellular cleft were occasionally found since 90 min
      and became significant 120 min after. However, in the CO2 pneumoperitoneum group
      bulging up of mesothelial cells was evident immediately at the time of filling of
      CO2, intercellular spaces could be found 30 min later, 60 min later intercellular
      cleft deep to the underlying basement membrane could be seen and the basement
      membrane lost its continuity and became uncovered, and 120 min later such changes
      became more significant and a small amount of lymphocytes and macrophages were
      found in the intercellular clefts. CONCLUSION: Carbon dioxide pneumoperitoneum
      during laparoscopic surgery causes significant morphological changes in the
      peritoneum duration of insufflation dependently.

PMID- 16638322
TI  - [One-stage total thoracoabdominal aorta replacement with four branch vessel
      prosthesis under deep hypothermic cardiopulmonary bypass and subsection
      circulatory arrest].
AB  - OBJECTIVE: To summarize the experience in one-stage total thoracoabdominal aorta
      replacement with four branch vessel prosthesis under deep hypothermic
      cardiopulmonary bypass and subsection circulatory arrest. METHODS: From August
      2003 to May 2005 38 patients with thoracoabdominal aortic disease, including
      severe extensive thoracoabdominal aorta of Crawford II type (n = 4), chronic
      Stanford type B dissecting aneurysm (n = 24), chronic Stanford type A dissecting
      aneurysm (n = 5), and Marfan's syndrome with chronic Stanford type B dissecting
      aneurysm (n = 5), 25 males and 13 females, aged 40 +/- 9 (22-58), underwent one
      stage total thoracoabdominal aorta replacement with four branch vessel prosthesis
      under deep hypothermic cardiopulmonary bypass and subsection circulatory arrest.
      RESULTS: Two patients died during the early post-operational period with a
      mortality of 5.26%. Four patients showed cerebral complications with an incidence
      of 10.5% and were cured after hydration therapy. Acute kidney dysfunction
      occurred in 2 patients and was cured by hemodialysis. CONCLUSION: With simplified
      operational procedure, one-stage total thoracoabdominal aorta replacement with
      four branch vessel prosthesis under deep hypothermic cardiopulmonary bypass and
      subsection circulatory arrest significantly shortens the ischemic time of brain,
      spinal cord, and other major organs and has an excellent effect.

PMID- 16638323
TI  - [A new mutation in COL1A1 gene in a family with osteogenesis imperfecta].
AB  - OBJECTIVE: Osteogenesis imperfecta (OI) is a congenital disease of connective
      tissue of increased bone fragility and low bone mass, most often caused by single
      amino acid substitution of glycine residues in the collagen, type I, alpha 1
      protein (COL1A1) gene or the collagen, type I, alpha 2 protein (COL1A2) gene,
      encoding type I procollagen chains. We describe here the clinical, biochemical,
      and molecular characterization of a family with type I OI in China and would like
      to explore whether the biochemical characterization of OI in China is different
      from that in other countries. METHODS: Through clinical research, we study the
      clinical characteristic of the OI household. Genomic DNA was isolated from
      peripheral blood lymphocytes of the proband and his family members by saturation
      hydroxybenzene-chloroform methods; amplification of target COL1A1 gene by
      Polymerase chain reaction with 23 pairs of different primers; purification;
      direct sequencing of the Polymerase chain reaction product. According to the
      mutation site, we took restriction enzyme analysis to 50 normal control people.
      RESULTS: We found a G and A heterozygosis mutation at the exon 48 causing an a1
      (I) p. G1157D substitution in the proband and his sister who is also a sufferer
      of OI. At the same time, other normal people in the family and other normal
      control people do not have this change. CONCLUSION: This is the first delineation
      of an aspartic acid substitution in new site of the a1 (I) chain causing
      nonlethal osteogenesis imperfecta. Only nine aspartic acid substitution in type I
      collagen has been fully reported in the world. Now we revealed a new nosogenesis
      of OI. Since only few of nucleotide changes in type I collagen glycine codons
      would result in an aspartic acid substitution, these are predicted to be
      infrequent. Furthermore, it is possible to suggest that nosogenesis of OI in
      china is different from other countries.

PMID- 16638324
TI  - [Surgical diagnosis and treatment of Castleman's disease].
AB  - OBJECTIVE: To investigate the clinical features and treatment of the surgical
      tumors associated with Castleman's disease. METHODS: The clinical data of 20
      patients with Castleman's disease, 6 males and 14 females, aged 39 (15-70), with
      the tumor size ranging from 2 cm x 3 cm to 10 cm x 9 cm, and with the tumor
      located in the mediastinal cavity (n = 6), retroperitoneal area (n = 2),
      abdominal cavity (n = 1), adrenal area (n = 1), neck and armpit (n = 2), and
      multi-centers (n = 2), were analyzed. RESULTS: Nineteen of the 20 patients
      underwent surgical resection of the tumor or lymph node. All were diagnosed as
      Castleman's disease by pathological examination. Most of the tumor was benign.
      Three cases were diagnosed as with paraneoplastic pemphigus. CONCLUSION: Surgical
      resection of the tumor is the first choice for treatment of Castleman's disease.

PMID- 16638325
TI  - [Inoculation of the cells transfected with IP10 inhibited experimental tumor
      metastases in vivo].
AB  - OBJECTIVE: To explore the inhibitory effects of IP10 on the experimental tumor
      metastases of a mammary carcinoma cell line 4T1 in vivo. METHODS: 4T1 cells were
      transfected with pcDNA3-IP10 plasmid and the positive clones (IP10-4T1) were
      screened in the presence of G418. The parental 4T1 cells and 4T1 cells
      transfected with pcDNA3 (pcDNA3-4T1) were used as controls. The expression of
      IP10 mRNA was examined with RT-PCR. The chemotactic activity of the cell-cultured
      supernatant for the activated lymphocytes was assessed with chemotaxis assay. All
      BALB/c mice were divided into 3 equal groups: IP10-4T1, parental 4T1 and pcDNA3
      4T1 (6 mice in each group). Seven days after mice were inoculated with 2 x 10(6)
      4T1, pcDNA3-4T1 or IP10-4T1 cells, 1 x 10(5) 4T1 cells were injected into mice in
      tail vein. On day 14 tumors were sectioned. On day 28 mice were sacrificed and
      the lung weight, metastatic forci on the lung surface, disseminated metastases in
      the lungs and the number of clonogenic metastases of 4T1 cells were observed. The
      splenocytes were isolated from tumor-bearing mice, and the cytotoxicity of the
      splenocytes was evaluated by CFSE/7-AAD method. RESULTS: The transcription of
      IP10 mRNA increased in IP10-4T1 cells compared to parental 4T1 and pcDNA3-4T1
      cells (P = 0.002). Moreover, accumulated lymphocytes migrated to the supernatants
      of IP10-4T1 cells, which can be abrogated by anti-CXCR3 (P < 0.05). Compared to
      controls, inoculation of IP10-4T1 cells resulted in the decreased disseminated
      metastases as indicated by dramatically reduced lung metastatic forci on the
      surface of the lungs; the lung weight was lighter (IP10-4T1, 0.27 +/- 0.02 g v.s.
      4T1, 0.48 +/- 0.08 g and pcDNA3-4T1, 0.43 +/- 0.16 g, P = 0.021); the number of
      clonogenic metastatic 4T1 cells enumerated in ten fields decreased greatly (IP10
      4T1, 2.6 +/- 1.7 v.s. 4T1, 34 +/- 6.3 and pcDNA3-4T1, 33 +/- 2.3, P < 0.05);
      histological assay showed that metastasis was not found in the lungs of the 4/6
      of mice in IP10-4T1 group, and was seen in all the mice of parental 4T1 and
      pcDNA3-4T1 groups. The splenocytes from the mice inoculated with IP10-4T1 cells
      exhibited stronger cytotoxic activity against 4T1 target cells at different
      ratios of effector versus target cells (3:1, 9:1, 27:1) than controls (P < 0.05).
      CONCLUSION: IP10 expressed locally could inhibit disseminated metastasis of
      circulating 4T1 tumor cells by enhancing anti-tumor cellular immune responses.

PMID- 16638326
TI  - [Inhibition of pulmonary fibrosis by doxycycline: an experiment with mice].
AB  - OBJECTIVE: To investigate the effect of doxycycline, an antimicrobial antibiotic
      inhibiting type IV collagenase, on the development of pulmonary fibrosis induced
      by bleomycin (BLM) in mice. METHODS: Gelatin zymography assay was used to detect
      the secretion of 72,000 and 92,000 type IV collagenase in HT-1080 cells and the
      activity of these enzymes in vitro. Experimental pulmonary fibrosis was induced
      by intra-tracheal administration of BLM in anesthetized mice. Total lung collagen
      content was determined by hydroxyproline assay. The histopathological changes of
      pulmonary fibrosis were evaluated by image analysis. RESULTS: The secretion of
      72,000 and 92,000 type IV collagenase in HT-1080 cell was markedly inhibited by
      doxycycline at concentrations of 0.1 mg/ml and 0.05 mg/ml. The activity of type
      IV collagenase in vitro was also suppressed by doxycycline. The hydroxyproline
      level in the lung was decreased in mice treated with doxycycline at the dose of
      100 mg/kg, down to 34.7% of that of the BLM model group. As shown by image
      analysis, the extensiveness of fibrotic lesions, the thickness of interalveolar
      septa, and the accumulation of nucleated cells were decreased in doxycycline
      treated group in comparison with BLM model group. CONCLUSION: This study provides
      evidence that doxycycline shows inhibitory effect on BLM induced pulmonary
      fibrosis.

PMID- 16638327
TI  - [Effect of beta-adrenergic agonist on alveolar fluid clearance in acute lung
      injury: an experiment with rats].
AB  - OBJECTIVE: To determine the effect of dobutamine, a beta-adrenergic agonist, on
      the alveolar fluid clearance (AFC) in acute lung injury (ALI). METHODS: Thirty
      two male Sprague-Dawley rats were randomly divided into four equal groups: normal
      control group; ALI group, infused with endotoxin to induce ALI; dobutamine
      control group, receiving sustained intravenous injection of dobutamine at the
      dose of 5 microg/kg/min, and dobutamine treatment group, receiving sustained
      intravenous injection of dobutamine at the dose of 5 microg/kg/min after the
      administration of endotoxin. Experiment began 45-60 minutes after the circulation
      was stable. Blood pressure was measured and blood gas analysis was conducted at
      the beginning of the experiment and one hour later. Perfusion fluid with (125)I
      albumin with the radioactivity of 1.5 microCi/ml was perfused into the lung. One
      hour after the mechanical ventilation the mice were killed and their lungs were
      taken out. Alveolar fluid was taken out to calculate the AFC by single nuclide
      tracer technique. RT-PCR was used to detect the expression of alpha, beta, and
      gamma-rat epithelial sodium channel (rENaC) mRNA. RESULTS: (1) The AFC of ALI
      group was 14.0 +/- 1.2%, significantly lower than that of the normal control
      group (21.0 +/- 3.9%, P < 0.05). (2) The AFC of the dobutamine control group was
      26.6 +/- 1.6%, significantly higher than that of the normal control group (P <
      0.05). and the AFC of the dobutamine treatment group was 20.0 +/- 3.9%,
      significantly higher than that of the ALI group (P < 0.05). (3) The expression of
      a-rENaC mRNA was 1.40 +/- 0.40 in the ALI group and was 1.38 +/- 0.13 in the
      dobutamine treatment group, both significantly higher than those in the
      dobutamine control group (1.01 +/- 0.14) and in the normal control group (0.44 +/
      0.11, all P < 0.05). The expression of beta-rENaC mRNA was 0.70 +/- 0.8 in the
      ALI group was 0.71 +/- 0.17 in the dobutamine treatment group, both significantly
      higher than those in the dobutamine control group (0.58 +/- 0.12) and in the
      normal control group (0.44 +/- 0.11, all P < 0.05). There were not significant
      differences in expression of alpha and beta-rENaC mRNA between the normal control
      group and dobutamine control group, and between the ALI group and dobutamine
      treatment group (both P > 0.05). (4) The gamma-rENaC mRNA expression was 0.90 +/-
      0.19 in the dobutamine control group and was 0.97 +/- 0.15 in the dobutamine
      treatment group, both significantly higher than that in the normal control group
      (0.69 +/- 0.10) and in the ALI group (0.70 +/- 0.32) (all P < 0.05). CONCLUSION:
      Able to upregulate the gamma-rENaC expression and improve the AFC in acute lung
      injury, beta-adrenergic agonist may be beneficial to reduce lung edema in ALI
      patients.

PMID- 16638341
TI  - [Clinical analysis of radical retropubic prostatectomy: a report of 132 cases].
AB  - OBJECTIVE: To summarize the experience of radical retropubic prostatectomy (RRP)
      and the multi-factors which influence on the prognosis and long life quality.
      METHODS: From January 1993 to March 2005, 132 cases radical retropubic
      prostatectomy were performed. The patients were divided into 2 groups: the early
      group and recent group. Eleven items in peri-operative time and follow up results
      were analysed. The erection function of 78 cases were investigated with
      international index of erectile function 5 score. In these patients, nocturnal
      electrobioimpedance volumetric assessment (NEVA) were observe in 19 cases.
      RESULTS: Comparing of the 2 groups, the index connected with operative skill
      changed to optimization. No one died of prostate cancer in 63 follow up patients.
      Nine cases showed biochemical failure with criterion as prostate specific antigen
      > 0.4 microg/L. Fifty patients passed urine normal post-operation in 6 months.
      Eight patients had stress incontinence and 5 had entire incontinence at 6 month.
      Four patients had vesical neck stricture. Another follow up result shows 33
      (58.9%) erection function recovered in 55 bilateral nerve-sparing operation and 7
      recovered in 22 of unilateral nerve-sparing operation. NEVA shows 14 cases with
      artery supply insufficient in whom 4 regained erection function and 5 cases vein
      leakage in whom no one recovered. CONCLUSIONS: The radical retropubic
      prostatectomy remains the procedure of choice for the cure of localized prostatic
      cancer. The keys for the operation are anatomic dissection, preservation of the
      neurovascular bundle and good skill. These are also important for a good life
      quality for the patients.

PMID- 16638343
TI  - [Prevention of incontinence after radical prostatectomy].
AB  - OBJECTIVE: To discuss the effect of urine control after radical retropubic
      prostatectomy by preserve the membranous part of sphincter urethrae and the
      neurovascular bundle, or to rebuild the bladder neck. METHODS: The radical
      retropubic prostatectomy was performed on a total of 32 cases of prostate cancer.
      We preserve the membranous part of sphincter urethrae and the neurovascular
      bundle lateral to the prostate. We evaginate the posterior wall of the bladder
      adequately and make an additional folding stitch to rebuild the bladder neck.
      RESULTS: The follow up is of 6-72 months. All patients could void without
      difficulty, no tumor recurrence and only 2 cases occurred slight incontinence.
      Other 30 cases regained the ability of controlling their urinations within 6
      months. CONCLUSIONS: The incontinence after radical retropubic prostatectomy
      could be reduced by the method of preserving the membranous part of sphincter
      urethrae and preserving the neurovascular bundle lateral to the prostate in
      operation. It could also be avoided by evaginate the posterior wall of the
      bladder adequately and make an additional folding stitch to the bladder neck.

PMID- 16638344
TI  - [Relationship between screening by stratifying cases into groups on prostate
      specific antigen level and the positive rate of transrectal ultrasound guided
      systematic sextant prostate biopsy].
AB  - OBJECTIVE: To evaluate the detection of prostate cancer in different prostate
      specific antigen (PSA) level and the predict value of PSA, digital rectal
      examination (DRE), transrectal ultrasound scan (TRUS) and PSA density (PSAD).
      METHODS: The clinical data of 634 cases who had underwent transrectal ultrasound
      guided systematic sextant prostate biopsies between April 1996 to December 2002
      due to being suspicious of prostate cancer were retrospectively analyzed. The
      detection of prostate cancer in different PSA groups, namely PSA < or = 4.0, 4.1
      , 10.1-, > 20.0 microg/L, and the predict values of PSA, DRE, TRUS and PSAD were
      statistically analyzed using t test, chi2 test and logistic regression analysis.
      RESULTS: The rates of prostate cancer detection in different PSA groups were
      11.6%, 26.8%, 39.8% and 68.6%, respectively. The higher the PSA, the higher the
      rate of prostate cancer detection, the same was the positive predictive value of
      DRE and TRUS. The sensitivity and specificity of PSA > 4.0 microg/L were 93.0%
      and 33.0%, and the efficiency of DRE and TRUS were very low. Logistic regression
      analysis indicated that PSAD was the most risk factor of prostate cancer in the
      group of PSA 4.1-20.0 microg/L (OR = 687.09 +/- 646.96, P = 0.000). CONCLUSIONS:
      The rates of prostate cancer detection in different PSA groups are different
      compared with other countries. The screening roles of DRE and TRUS are dependent
      on PSA level. Utilization of the screening protocol which to stratify cases into
      three PSA groups, namely PSA < or = 4.0, 4.1 - 20.0, > 20.0 microg/L, can elevate
      the positive rate of prostate biopsies without sacrificing cancers detected.

PMID- 16638345
TI  - [Prediction of the stage of patients with prostate cancer by the combination of
      serum prostate specific antigen and Gleason score].
AB  - OBJECTIVE: To explore the method of predicting the stage of prostate cancer with
      serum prostate-specific antigen (PSA) and pathological grade. METHODS: One
      hundred and eighty-seven patients were studied retrospectively with prostate
      cancer diagnosed by systemic biopsy in our hospital. The rank correlation
      analysis, rank sum test and stepwise discriminant multivariate analysis were used
      to assess the correlation of serum PSA level, ratio of free PSA to total PSA
      (FPSA/TPSA ratio) with Gleason score (GS) and stage. RESULTS: Serum PSA level
      increased with GS for prostate cancer patients (r = 0.369, P < 0.001). With
      increasing stage, serum PSA level and GS increased (r = 0.398, 0.530, P < 0.001).
      Overall, FPSA/TPSA ratio was not correlated with stage (P > 0.70), but a
      significant negative correlation was demonstrated between them when serum PSA <
      or = 10 microg/L (r = -0.600, P < 0.05). When serum PSA > 20 microg/L, 67% - 87%
      patients with prostate cancer may be stage C or D. The equation using serum PSA
      and GS to predict the stage of patients with prostate cancer was: x = -3.488 +
      0.041 x PSA + 0.428 x GS. CONCLUSIONS: Serum PSA level is positively correlated
      with GS for prostate cancer patients. Serum PSA level and GS are positively
      correlated with stage. A negative correlation between FPSA/TPSA ratio and stage
      is demonstrated when serum PSA < or = 10 microg/L. The combination of serum PSA
      and GS may predict the stage of patients with prostate cancer.

PMID- 16638346
TI  - [The usefulness of percentage of free prostate specific antigen/prostate specific
      antigen density in the diagnosis of prostate cancer].
AB  - OBJECTIVE: To investigate the usefulness of percentage of free prostate specific
      antigen (FPSA/TPSA) in serum/PSA density [(F/T)/PSAD] in the diagnosis of
      prostate cancer. METHODS: Two hundred and four patients who had been carried out
      transrectal ultrasound guided prostate biopsy, were involved in this study. Among
      them, 90 patients were proved to be suffering from prostate cancer, and other 114
      patients were identified as benign prostate hypertrophy. The effect of total
      serum PSA level, FPSA/TPSA, PSAD and (F/T)/PSAD in the diagnosis of prostate
      cancer were investigated, and at the same time, selecting patients who should be
      carried out a prostate biopsy. RESULTS: The mean values of (F/T)/PSAD were
      significantly lower for patients with prostate cancer in different PSA levels
      (<4.0, 4.0-, 10.1-, >20.0 microg/L), when compared with benign prostate
      hypertrophy patients. This difference has arrived statistical significance (P <
      0.05). (F/T)/PSAD could provide higher specificity for diagnosing prostate cancer
      than FPSA/TPSA or PSAD. Among all patients, at the same higher sensitivity (about
      90%), the specificity of FPSA/TPSA, PSAD and (F/T)/PSAD was 31.6%, 45.6% and
      64.0%, respectively. At the same time, it was suggested that clinicians use
      different cutoffs for (F/T)/PSAD in different PSA level. When PSA level of
      patients was no more than 4.0 microg/L, 2.5 as the commended cutoff for
      (F/T)/PSAD was preferred; if PSA level was between 4.0 microg/L and 20.0
      microg/L, 0.8 was a more suitable cutoff; 0.5 also could be taken as an
      appropriate cutoff in case of PSA level being higher than 20.0 microg/L.
      CONCLUSIONS: Keeping high sensitivity, using of (F/T)/PSAD can improve the
      diagnostic specificity of prostate cancer significantly.

PMID- 16638347
TI  - [Induction of apoptosis by mifepristone in androgen-independent prostate cancer
      cell lines in vitro].
AB  - OBJECTIVE: To investigate the effects of mifepristone on cell proliferation of
      human androgen-independent prostate carcinoma cell lines DU-145, PC-3 in vitro
      and the possible mechanisms involved. METHODS: The A values of the prostate
      cancer cells DU-145 and PC-3 in each group with various concentrations (1, 10,
      50, 100 micromol/L) of mifepristone at various time intervals (24-120 h) were
      detected with the colorimetric 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl
      tetrazolium bromide assay. The apoptosis rates of the DU-145 and PC-3 cells
      treated with 10 micromol/L of mifepristone for 24 h and 48 h were assessed by
      flow cytometry analysis technique. Immunohistochemical technique was used to
      determine the expression of bax, bcl-2 and vascular endothelial growth factor
      (VEGF) proteins after treatment with 10 micromol/L of mifepristone. RESULTS: The
      A values of the cancer cells treated with 1 micromol/L of mifepristone were
      similar to that of controls, while those of the cells treated with 10 micromol/L,
      50 micromol/L and 100 micromol/L of mifepristone were significantly different
      from that of controls (P < 0.01). Mifepristone markedly inhibited cell
      proliferation of prostate cancer cells DU-145 and PC-3 on a dose- and time
      depending manner. The apoptosis rates of 10 micromol/L mifepristone for DU-145
      cell line at 24 h, 48 h were respectively 15.3%, 30.4% with flow cytometry method
      and then PC-3 cell line were respectively 22.2%, 32.0%. Immunohistochemical
      technique showed the expression of bcl-2 and VEGF in the DU-145 and PC-3 cells
      treated with 10 micromol/L of mifepristone were significantly decreased, and the
      expression of bax was increased. CONCLUSIONS: Mifepristone can induce apoptosis
      of androgen-independent prostate cancer cell lines DU-145 and PC-3 in vitro. The
      apoptosis effect is time-and-dose dependent. Mifepristone could initiate a cell
      death command via apoptotic pathways decreasing the expression of VEGF protein,
      downregulating the expression of bcl-2 protein and increasing the expression of
      bax protein.

PMID- 16638348
TI  - [Percutaneous nephrolithotripsy with pneumatic and ultrasonic power under B-type
      ultrasound guidance for treatment of renal calculi in non-dilated collecting
      system].
AB  - OBJECTIVE: To evaluate the efficacy and safety of management of renal stone in
      non-dilated collecting system by percutaneous nephrolithotripsy (PCNL) under
      ultrasound guidance. METHOD: From September 2003 to April 2005, 132 cases of
      renal stone in non-dilated collecting system were performed by percutaneous
      nephrolithotripsy. A stent was first inserted into the pelvis through cystoscope,
      and saline was instilled to dilate collecting system. Antegrade percutaneous
      access was obtained by B-type ultrasound guidance. A combination pneumatic and
      ultrasonic lithotrite were used to disintegrate and remove stone under direct
      vision. Clinical data including operation time, complications and stone free rate
      were analyzed retrospectively. RESULTS: The percutaneous renal access was
      successfully established under B-type ultrasound guidance in all patients,
      immediate phase I lithotripsy was performed in 129 cases and delayed phase II
      lithotripsy in 3 cases. Operation time ranged from 70 to 130 minutes, average
      time was (89 +/- 11) minutes, 3 cases were supported by blood transfusion, severe
      complications did not occur during nephrolithotripsy. Stones were cleared in 114
      out of 132 cases (86.4%) during immediate phase I lithotripsy, residual stone
      fragment was found in 18 cases who received second PCNL or adjuvant
      extracorporeal shock wave lithotripsy. CONCLUSION: The management of renal stone
      in non-dilated collecting system using PCNL appears to be efficacious and safe
      under B-type ultrasound guidance.

PMID- 16638350
TI  - [Using of percutaneous nephrolithotomy in pediatric urolithiasis].
AB  - OBJECTIVE: To assess the safety and efficacy of percutaneous nephrolithotomy
      (PCNL) using ureteroscope and pneumatic intracorporeal lithotripsy in the
      pediatric age group. METHODS: Twenty-two renal units in 15 patients underwent
      PCNL at our institute. The patients were all under 14 years old. The average age
      was 9 years (range 5-14 years). There were 7 bilateral, 8 multiple, and 5
      staghorn calculi. The average calculus size was 2.0 (0.9-4.5) cm. The PCNL was
      done with an X ray-guided peripheral puncture, a planned staged approach in some
      cases, and minimal tract dilatation with the use of an ureteroscope and pneumatic
      intracorporeal lithotripsy. RESULTS: Complete stone clearance was achieved in 20
      renal units, giving an overall clearance rate of 91%. Minor pyrexia (< 39 degrees
      C, < 2 days) was seen in 14 patients, whereas serious pyrexia was seen in 1. The
      average fall in hemoglobin was 10 g/L, but none of the patients required blood
      transfusion. CONCLUSIONS: It is safe and effective to cure pediatric urolithiasis
      with percutaneous nephrolithotomy using ureteroscope and pneumatic intracorporeal
      and pneumatic intracorporeal lithotripsy.

PMID- 16638355
TI  - [Early outcome of orthotopic heart transplantation: a report of 21 cases].
AB  - OBJECTIVE: To report the preliminary experience of 21 orthotopic heart
      transplantations without early death. METHODS: Between April 2002 and June 2005,
      21 patients underwent orthotopic heart transplantation. Recipients' pulmonary
      vascular resistance ranged from 3.0 to 5.9 wood units [mean (4.3 +/- 1.4) wood
      units]; Stanford myocardial protective solution or HTK solution was perfused for
      donor heart myocardial preservation, donor heart cold ischemic period ranged from
      52 to 310 min [mean (81 +/- 23) min]; Three patients had previous cardiac
      operations under cardiopulmonary bypass, conventional Stanford orthotopic cardiac
      transplantation in 20 cases and total heart technique in 1 case; Recipients
      received simulect preoperatively and cyclosporine A, cellcept and prednisone
      postoperatively for prevention of acute allograft rejection; Patients received
      appropriate medical control of hypertension, hyperglycemia, hypercholesterolemia
      and uricacidemia. RESULTS: Acute right heart failure in 3 cases and pericardial
      effusion in 4 cases were observed at the early postoperative stage, but no any
      infection and acute rejection were found. All patients survived with good life
      quality. CONCLUSIONS: Heart transplantation may produce satisfying early results.
      Suitable selection of recipients with low pulmonary vascular resistance,
      excellent donor heart conservation, practised anastomotic technique, proper
      immunosuppression treatment and efficient postoperative management are key
      measures of orthotopic heart transplantation with excellent early outcome.

PMID- 16638357
TI  - [Resection for lung cancer invading the superior vena cava].
AB  - OBJECTIVE: To analyze the feasibility and the value of resection for lung cancer
      invading the superior vena cava (SVC). METHODS: Between 1988 and 2005 the data of
      31 patients who underwent resection were analyzed retrospectively. The
      reconstruction was done using simple suture, pericardial patch or prosthetic
      replacement. Postoperative morbidity, long-term survival were examined using the
      Kaplan-Meier method (Log rank test) and the COX model for survival. RESULTS:
      Seventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated
      small cell carcinomas were resected. There were 13 partial SVC resection, the
      reconstruction was done using a simple running in 5 patients, and a pericardial
      patch in 8 patients. Eighteen patients underwent complete resection of SVC with
      prosthetic replacement. The time of clamping the SVC system was from 8 to 35
      minutes for complete resection patients, while the time was from 3 to 15 minutes
      for partial resection patients. One patient didn't clamp the SVC. Postoperative
      morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival
      rates were 61%, 33% and 21%, respectively, with median survival at 31 months.
      Survival rate of patients with N2 disease was obviously lower than those with
      localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was
      42 and 13 months respectively. There were no significant effects on overall
      survival with pathologic features and surgery methods. Survival rate of patients
      with induction chemotherapy before operation or intraoperative chemotherapy was
      higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median
      survival was 39 and 14 months respectively. CONCLUSIONS: The resection of the SVC
      for involvement by lung cancer can be performed in selected patients, especially
      for those with localized (N0/N1) nodal disease. Induction chemotherapy should be
      performed.

PMID- 16638358
TI  - [Value of carbon-11 choline positron emission tomography in patients with
      pulmonary abnormalities].
AB  - OBJECTIVE: To assess the value of carbon-11 choline (CH) positron emission
      tomography (PET) in patients with pulmonary nodules. METHODS: From September 2002
      to December 2004, 39 patients with pulmonary nodules were imaged with CH-PET. CH
      PET data was analyzed by visual method and semiquantitative method. When
      pulmonary nodules with abnormal CH uptake appeared in PET scans confirmed by
      visual method, their maximum and mean standard uptake value (SUVmax and SUVmean)
      were measured using semiquantitative method. Diagnoses were confirmed by surgery
      or biopsy and follow-up survey. RESULTS: Twenty-four cancerous and 3 inflammatory
      nodules and 1 bronchogenic cyst were detected by CH-PET and were diagnosed
      malignant with visual method. Three bronchial alveolar carcinoma, 2 metastatic
      tumor from kidney and colon, 3 fibrous nodules, 1 cryptococcosis, 1 hamartoma and
      1 sclerosing hemangioma showed nothing abnormal in PET scans. For identification
      of pulmonary nodules with CH-PET, the sensitivity was 89% (24/29), the
      specificity was 60% (6/10), and the accuracy was 77% (30/39). There were
      differences in SUV between 8 squamous cell carcinomas and 9 adenocarcinomas (Z = 
      2.937, -2.887, P < 0.01). In diagnosing 70 resected enlarged lymph nodes beyond 1
      cm in 17 lung cancer patients, CH-PET had the sensitivity of 86% (25/29), the
      specificity of 90% (37/41), and the accuracy of 89% (62/70). CH-PET confirmed 7
      distant metastases in 25 lung cancer patients. In 5 cases suspected brain
      metastases CH-PET identified 2 cases positive correctly. CONCLUSIONS: CH-PET can
      confirm malignant pulmonary nodules, but still there were false positive and
      false negative cases. CH-PET can evaluate N stage effectively in patients with
      lung cancer. CH-PET can depict brain metastases accurately.

PMID- 16638359
TI  - [Classification and surgical treatment of intrathoracic esophageal injury caused
      by foreign body].
AB  - OBJECTIVE: To investigate the classification criterion and surgical treatment
      strategy of intrathoracic esophageal injury caused by foreign body. METHODS:
      Eighty-four patients with intrathoracic esophageal injury caused by foreign body
      in our department from January 1980 to April 2004 were divided into 4 grade:
      grade I was non-penetrated injury of esophagus (18 cases); grade II was
      esophageal perforation with mild mediastinitis (39 cases); grade III was
      esophageal perforation with severe intrathoracic infection (17 cases); grade IV
      was aortoesophageal fistula (10 cases). Based on the degree of esophageal injury
      and the extension of inflammation, operative procedures were selected including
      esophagotomy, esophageal reparation, esophagectomy, mediastinal drainage,
      reparation of fistula and replacement of aorta. RESULTS: Patients in grade I and
      II were all cured . One death occurred in grade III (1/17), the same in Grade IV
      was 9 (9/10). CONCLUSIONS: Classification of esophageal injury caused by foreign
      body is helpful to the decision of surgical treatment strategy. The prevention of
      aortoesophageal fistula is the key point of reducing of mortality.

PMID- 16638360
TI  - [Early-mid-phase microsurgery for ruptured cerebral anterior circulating
      aneurysm].
AB  - OBJECTIVE: To evaluate clinical strategy and effect of early-mid-phase
      microsurgery for ruptured cerebral anterior circulating aneurysm. METHODS:
      Seventy-five patients presenting with anterior circulating aneurysmal
      subarachnoid hemorrhage (SAH) underwent early-mid-phase (within 3 days or 3-10
      days) microsurgical clipping at Huashan Hospital between January 2001 and August
      2004. Glasgow outcome scale (GOS) was conducted to evaluate patients' outcomes.
      RESULTS: Of 81 intracranial aneurysms, 77 lesions were clipped successfully, and
      4 were wrapped. Good outcome was achieved in 53 cases, mild disability in 9
      cases, severe disability in 7 cases, persistent vegetative state in 3 cases, and
      3 patients (4%) died after surgery. The difference of GOS was statistically
      significant between patients in Hunt and Hess Grade I-III and Grade IV-V.
      However, there was no significant difference between early surgery and metaphase
      surgery. CONCLUSIONS: Early-mid-phase microsurgery for ruptured cerebral anterior
      circulating aneurysm is considered the feasible opinion.

PMID- 16638361
TI  - [Gamma knife for hypersecreting pituitary adenoma: analysis of 120 cases].
AB  - OBJECTIVE: To estimate the efficacy of Gamma knife radiosurgery (GKR) especially
      as a primary surgical treatment for hypersecreting pituitary adenoma. METHODS:
      One hundred and twenty cases with hypersecreting pituitary adenoma had been
      treated by Gamma knife radiosurgery. The clinical date had been analysed
      retrospectively. The tumor margin was covered by an isodose ranging from 45% to
      70%. The margin dose was 15 to 32 Gy (mean 28.5 Gy) and the maximum dose varied
      from 35 to 70 Gy (mean 45.5 Gy). The total number of isocenter was 165 (mean 1
      3). RESULTS: One hundred and eleven cases had been followed-up by hormone level,
      and 104 cases had been followed-up by image of MRI. The mean follow-up duration
      was 12-72 months (mean 36 months). The control rate of hormone level was 48.6%,
      the control rate of tumor growth was 96.2%, the incidence of hypopituitarism was
      in 2.7% and the incidence of tumor apoplexy was in 0.9% in followed-up cases.
      CONCLUSIONS: As a primary surgical treatment for hypersecreting pituitary
      adenoma, GKR can be effective and safe in controlling tumor growth and inducing
      hormonal normalization.

PMID- 16638362
TI  - [A study on outcome of surgical treatment for focal dystonia].
AB  - OBJECTIVE: To analysis the outcome of stereotactic nucleus lesioning for focal
      dystonia patients. METHODS: Twenty-three focal dystonia patients were divided
      into 2 groups according to etiological factor. Stereotactic nucleus lesioning was
      performed for 10 primary dystonia patients of group A and 13 secondary patients
      of group B. The change of motor function was investigated and matched between 2
      groups after 6 months follow-up. RESULTS: Significant improvement of motor
      abilities was observed in patients of group A. The mean improvement of patients
      of group B was 43.8%. And the individual difference of improvement was obvious in
      patients of group B. CONCLUSIONS: Stereotactic nucleus lesioning displays a
      satisfactory therapeutic effect for patients of writer's cramp. The efficacy of
      nucleus lesioning for secondary focal dystonia patients depends on the extensive
      of brain functional lesion. A structurally normal brain is not certainly a
      predictor of good response to surgical treatment.

PMID- 16638369
TI  - Pityriasis rosea-like adverse reaction: review of the literature and experience
      of an Italian drug-surveillance center.
AB  - Pityriasis rosea is a common, acute eruption of uncertain etiology. A rash very
      similar to this idiopathic disease is also attributed to several drugs, and
      recovery, which depends on withdrawal of the responsible drug, can be delayed by
      its late identification. A prospective study to record all cases of adverse
      cutaneous reactions presenting with pityriasis rosea like manifestations was
      conducted at the center for drug-surveillance of the dermatology department of
      Cagliari University. We developed an intensive surveillance program from June
      2002 to May 2005, adopting the WHO Collaborating center for Drug Monitoring
      causality assessment criteria and algorithm. Eight cases, six male and two
      female, were studied in a 3-year period. None had previously suffered from drug
      intolerance or allergy. Clinical manifestations were very similar to pityriasis
      rosea. Responsible drugs were mainly angiotensin-converting enzyme inhibitors,
      alone or in combination with hydrochlorothiazide, followed by one case each for
      hydrochlorothiazide plus sartan, allopurinol, nimesulide, acetyl salicylic acid.
      Recovery was obtained in all cases with drug withdrawal. Final causality
      assessment was probable for all eruptions. Frequency of drug pityriasis rosea
      like eruptions is probably underreported. The mildness of the eruption, mimicking
      a very common and self-limiting disease does not prompt physicians to verify the
      use of medications until persistence, severity of lesions and itching require re
      evaluation of the original diagnosis.

PMID- 16638370
TI  - Increased expression of basic fibroblast growth factor in skin of patients with
      systemic sclerosis.
AB  - Increased collagen deposition is a hallmark of systemic sclerosis (SSc). Several
      fibrogenic cytokines play a role in this sclerosis. The role of basic fibroblast
      growth factor (bFGF), the most potent fibrogenic cytokine, is poorly understood
      in SSc. Skin biopsies from forearm of 13 patients with SSc and 3 normal
      individuals were analyzed by immunohistochemistry using avidin biotin-system to
      amplify the signal. In addition serum levels of bFGF were also measured in 30
      patients including these 13 and 23 healthy controls. Thirteen patients with SSc
      were all females and had a median age of 26.5 years, median disease duration of
      2.25 years. Of these thirteen, seven had diffuse and six had limited disease. The
      skin biopsies from patients showed increased expression of bFGF in the basal
      layer of epidermis, dermis (periappendageal, perivascular, matrix tissue) as
      compared to normal tissues. The expression of bFGF did not correlate with
      duration of disease or skin score. In contrast, only low levels of bFGF were
      detectable in 4/30 sera from SSc patients as compared to 3/23 from healthy
      controls (p = ns). Overexpression of bFGF in skin of patients with SSc along with
      normal serum levels suggests that bFGF probably acts in an autocrine or paracrine
      manner in fibrogenesis.

PMID- 16638371
TI  - A review of rituximab in cutaneous medicine.
AB  - The rituximab antibody is a genetically engineered chimeric murine/human
      monoclonal antibody directed against the CD20 antigen found on the surface of
      normal and malignant B lymphocytes. Rituximab is indicated for the treatment of
      patients with relapsed or refractory, low-grade or follicular, CD20-positive, B
      cell non-Hodgkin lymphoma. Rituximab is also commonly used to treat chronic
      lymphocytic leukemia, Waldenstrom's macroglobulinemia, and immune or idiopathic
      thrombocytopenic purpura (ITP). Rituximab is an effective treatment for primary
      cutaneous B-cell lymphoma and other cutaneous lymphomas. Rituximab is an
      effective treatment for mixed cryoglobulinemia. Rituximab is a promising
      treatment for systemic lupus erythematosus, dermatomyositis, pemphigus,
      vasculitis, and a variety of hematologic diseases. Black-box warnings on
      rituximab include fatal infusion reactions, tumor lysis syndrome, and severe
      mucocutaneous reactions. A variety of cardiac, pulmonary, renal, and hematologic
      side effects can occur. It commonly causes mild cutaneous side effect and rarely
      has caused paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid
      dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.

PMID- 16638372
TI  - Sjogren syndrome and systemic lupus erythematosus are distinct conditions.
AB  - Sjogren syndrome (SS) and systemic lupus erythematosus (SLE) are both collagen
      vascular diseases that can be accompanied by Ro antibodies. Clinical evidence
      suggests that they are wholly distinct diseases. SS is strongly linked to
      lymphoma while lupus is not. SS patients do not commonly exhibit photosensitivity
      even though anti-Ro antibodies circulate in their blood; SLE patients generally
      exhibit photosensitivity. SS does not respond to hydroxychloroquine in a
      reproducible fashion whereas SLE does. SS has not been linked to parvovirus B19,
      but SLE has. However, SS and SLE do have similarities. Their autoantibody
      profiles are similar. They effect women more than men and have similar HLA
      haplotypes and autoantibodies; this is not likely coincidence but it may not
      clinically relevant.

PMID- 16638373
TI  - Assessment of a blog as a medium for dermatology education.
AB  - Our first year experience with the use of a web log as a communication tool for
      our dermatology interest group at the University of Texas Medical Branch in
      Galveston (UTMB) is described. We find the UTMB Dermatology Interest Group Blog
      facilitates educational opportunities and serves as a dermatology resource for
      medical students, and improves communication. It is an educational innovation
      that could be adopted by other dermatology departments.

PMID- 16638374
TI  - Dermatology postgraduate training in Canada: CanMEDS competencies.
AB  - Medical residency education and the development of formalized training objectives
      in Canada have evolved continuously, especially with the introduction of the
      Canadian Medical Education Directions for Specialists (CanMEDS) competencies by
      the Royal College of Physicians and Surgeons of Canada (RCPSC) in 1996. In order
      to evaluate the effectiveness of implementation of CanMEDS competencies in
      Canadian postgraduate dermatology training programs from the residents'
      perspective, a comprehensive national survey of all Canadian core dermatology
      residents was conducted in June 2004. One hundred percent of core (PGY3-5)
      dermatology residents across the country (n = 48) completed the survey. Forty
      eight percent of residents were familiar with the CanMEDS competencies. Within
      the CanMEDS framework, the competencies were felt to be taught adequately by the
      following proportion of residents: medical expert (78 %), professional (66 %),
      communicator (52 %), collaborator (48 %), health advocate (48 %), scholar (48 %),
      and manager (28 %), with notable differences based on the year of training. This
      is the first national Canadian survey examining dermatology postgraduate
      education from the residents' perspective with a focus on CanMEDS competencies.
      While the RCPSC CanMEDS project implementation is presently in the faculty
      development phase, further work must be accomplished to enhance awareness of
      CanMEDS competencies and to incorporate these into dermatology residency programs
      across the country. Particular targeting of the roles perceived to be poorly
      taught is needed.

PMID- 16638375
TI  - Great toenail onychomycosis caused by Syncephalastrum racemosum.
AB  - Nondermatophyte molds are fungi found in soil and decaying plant debris and are
      generally considered to be uncommon or secondary pathogens of diseased nails.
      Prevalence rates of onychomycoses caused by nondermatophyte molds range between
      1.45 percent and 17.60 percent. The most common nondermatophyte molds associated
      with nail disease are Scopulariopsis, Scytalidium, Fusarium, Aspergillus and
      Onychocola canadensis. Syncephalastrum racemosum, a nondermatophyte mold, belongs
      to the class Zygomycetae. Only one well-documented case of human disease
      attributed to this organism has been described. We describe a 45-year-old man
      with culture proven toenail onychomycosis due to Syncephalstrum racemosum.

PMID- 16638376
TI  - Cutaneous Rosai-Dorfman disease.
AB  - Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a
      benign idiopathic histiocytic proliferative disorder that commonly involves the
      lymph nodes but secondarily may involve the skin. However, purely cutaneous
      disease without lymphadenopathy or internal organ involvement rarely may occur.
      We present case reports of three patients who presented with asymptomatic
      nonspecific enlarging skin nodules without evidence of lymphadenopathy or
      internal disease. Histopathologic examination of skin lesions in all patients
      showed proliferation of large histiocytes with phagocytosed inflammatory cells
      characteristic of Rosai-Dorfman disease. However, the diagnoses of
      dermatofibroma, other spindle cell neoplasm, infectious granulomatous process,
      and other xanthohistiocytic proliferations were also considered due to the
      presence of storiform spindle cells and foamy cells in the first case. One
      patient experienced regression during a course of oral steroids, while another
      patient cleared spontaneously. In the absence of massive lymphadenopathy
      characteristic of Rosai-Dorfman disease, the diagnosis of purely cutaneous Rosai
      Dorfman disease may be complicated by the rarity, non-specific clinical
      appearance of skin lesions, and broad histopathological differential diagnosis of
      this disorder. A high index of suspicion of the clinician and pathologist is
      often required.

PMID- 16638377
TI  - Prurigo pigmentosa treated with doxycycline.
AB  - Prurigo pigmentosa is characterized by an inflammatory phase with pruritic
      erythematous papules and a resolution phase with reticulated pigmentation. It is
      not a well known entity except in Japan. We present a Turkish young man with
      prurigo pigmentosa treated with doxycycline.

PMID- 16638378
TI  - Lipoid proteinosis in a 12-year-old child: a report from west India.
AB  - A 12-year-old male child born of non-consanguineous parents presented with
      multiple skin lesions, hoarseness of voice, and episodes of epilepsy since early
      childhood. The findings of characteristic beaded eyelid margins, patchy alopecia
      of the scalp, hoarseness of voice, and epilepsy were consistent with a rare
      clinical diagnosis, lipoid proteinosis. Skin biopsies obtained from
      representative skin lesions were subjected to histology and electron microscopy.
      Light microscopy demonstrated PAS-positive diastase-resistant material in the
      papillary dermis of skin. Ultrastructure revealed granulo-filamentary aspect of
      the accumulated material. Although this rare autosomal recessive disorder has
      been described in the literature, its occurrence is rare in India.

PMID- 16638379
TI  - Acrokeratosis paraneoplastica (Bazex syndrome): case report and review of
      literature.
AB  - Acrokeratosis paraneoplastica of Bazex is a rare syndrome. This condition is a
      distinct skin marker of supra-diaphragmatic neoplasia. This syndrome is important
      because the cutaneous findings preceed the onset of symptoms referable to the
      underlying neoplasm by several months in majority of the cases. We report here a
      case of a 63-year-old cachectic female who had classic psoriasiform lesions of
      acrokeratosis of Bazex with underlying bronchogenic carcinoma of the right lung.

PMID- 16638380
TI  - Necrobiotic xanthogranuloma of the chest wall.
AB  - Necrobiotic xanthogranuloma is a rare disease that usually presents with
      indurated yellow red nodules or plaques in the dermis or subdermal tissues. The
      pathogenesis of this disease is unknown and the limited number of cases has made
      long-term studies difficult. We report the case of a 61-year-old woman seen in
      our office for a 5 x 5-cm lesion of her chest wall. Biopsies established a
      diagnosis of necrobiotic xanthogranuloma. The patient received 4 months of
      intralesional steroid injections without change in the lesion. The patient was
      also treated with colchicine for several months without improvement. Therefore,
      the lesion was surgically excised and the area was reconstructed with local
      advancement skin flaps. The patient has been followed for 2 years with no
      evidence of recurrence.

PMID- 16638381
TI  - An unusual tumor of the forearm.

PMID- 16638382
TI  - Chondroid syringoma of the arm: an unusual localization.
AB  - Chondroid syringoma (CS) is an uncommon, benign, sweat-gland tumor. The usual
      presentation is of an asymptomatic, slowly growing mass, typically located on the
      head and neck region. We present a case of a CS located in the right arm of a 43
      year-old woman. This tumor developed slowly over 8 years. The diagnosis of CS was
      made by histopathological examination; it showed an abundant chondroid stroma
      intermingled with a fibro-adipoid tissue. There was no recurrence after total
      excision of the tumor with a 2-year followup. The unusual localization of
      chondroid syringoma made an accurate preoperative diagnosis difficult and
      diagnosis was achieved only by microscopy. Surgical tumor excision remains the
      best therapeutic option to avoid relapses of this tumor. Close followup is
      recommended because malignant transformation, although rare, is possible.

PMID- 16638383
TI  - Langerhans cell histiocytosis of vulva.
AB  - Cutaneous involvement of the vulva by Langerhans cell histiocytosis in women
      older than 70 is a rare phenomenon. A tendency of the disease to involve genital
      areas, has been described. We present a case of a 72-year-old woman, who had
      cutaneous vulvar involvement by Langerhans-cell histiocytosis, diagnosed by
      biopsy. An immunohistochemical study is also described.

PMID- 16638384
TI  - Lipoid proteinosis: report of three familial cases.
AB  - Lipoid proteinosis is a rare autosomal recessive disorder; it presents in early
      childhood with hoarseness, skin infiltration and thickening with beaded papules
      on eyelid margins, and facial acneiform or pock-like scars. Although 250 cases
      have been reported until now, the occurrence of disease in siblings is very rare.
      We report three familial cases of lipoid proteinosis involving a brother and
      sister and their nephew.

PMID- 16638385
TI  - Eccrine porocarcinoma.
AB  - We present an unusual case of eccrine porocarcinoma in that diagnosis was delayed
      for many years after the initial lesion appeared, resulting in relatively large
      tumor.

PMID- 16638386
TI  - Type II lepra reaction: an unusual presentation.
AB  - Ulcers with maculo-papular rash are an unusual presenting feature of leprosy.
      They occur as result of neuropathy, type-2 lepra reaction or Lucio's phenomenon.
      The hall mark of type-2 reaction is erythema nodosum. Very rarely it manifests as
      ulcerative skin lesions. We describe one such unusual case of a young male who
      presented with multiple ulcers and maculo-papular rash over the legs, chest and
      abdomen. In addition to this, he had fever, heart murmur, pulmonary infiltrates,
      neuropathy, and deranged liver function. A clinical differential diagnosis of
      infective endocarditis and systemic nectrozing vasculitis was made. Skin biopsy
      showed dense inflammation with lepra bacilli consistent with type-2 lepra
      reaction.

PMID- 16638387
TI  - Scabies presenting with bullous pemphigoid-like lesions.
AB  - A wide range of clinical manifestations may be seen in scabies, from classic
      pruritic papules and burrows to secondary features such as impetigo. Bullus
      lesions are a less frequent. Twenty cases of scabies presenting with bullae have
      been reported so far in the medical literature. Differentiating this subtype of
      scabies from the immunobullous disease bullus pemphigoid is a diagnostic
      challenge. A 42-year-old man was referred to our dermatology outpatient clinic
      with 3-month history of severe pruritus and tense blisters affecting mainly the
      lower trunk, arms and legs. An initial biopsy was suggestive for bullous
      pemphigoid. Close physical examination revealed small excoriated papules and a
      few burrows on borders of the hands and wrists. Skin scraping of the lesions on
      wrists was positive for Sarcoptes scabiei. Another biopsy specimen from a recent
      blister revealed subepidermal bullae with fibrin and inflammatory cells,
      particularly eosinophils. Direct immunofluorescence exam was negative. The
      patient was treated with lindane lotion followed by crotamiton cream with near
      complete resolution of the lesions. Scabies must be considered in patients
      presenting with recent onset of unexplained pruritic bullous lesions. Biopsy and
      immunofluorescence studies together with skin scrapings for Sarcoptes scabiei
      could help to differentiate these cases from bullous pemphigoid. Antiscabietic
      treatment results in resolution of bullous lesions in the affected patients.

PMID- 16638388
TI  - Bilateral cutaneous leishmaniasis of upper eyelids: a case report.
AB  - An 11-year-old girl presented with a 6-month history of bilateral upper eyelid
      erythema, induration, and blepharitis resistant to conventional antibiotic
      therapy. The lesions gradually progressed to symmetrical ulcerative nodules
      within 3 months. Cutaneous smear and biopsy revealed numerous amastigotes in
      macrophage cells. Therapy with systemic pentavalent antimonial resulted in
      successful healing of lesions. We conclude that cutaneous leishmaniasis must be
      kept in mind in the differential diagnosis of bilateral chronic eyelid swelling
      in endemic regions of the world.

PMID- 16638389
TI  - Excision of epidermoid cysts with a minimal linear incision.

PMID- 16638390
TI  - Treatment of limited extent extramammary Paget's disease with 5 percent imiquimod
      cream.
AB  - Extramammary Paget's disease (EMPD) is a rare neoplastic condition of apocrine
      gland-bearing skin, which may be associated with internal malignancy. Although
      surgical excision is the generally accepted standard of care for EMPD, treatment
      with topical imiquimod 5 percent cream has reportedly been efficacious in
      clearing lesions. We report the case of a 78-year-old woman with biopsy-proven
      EMPD of the thigh treated successfully with imiquimod application thrice weekly
      for 16 weeks.

PMID- 16638391
TI  - Biographies in dermatology: an appraisal.

PMID- 16638392
TI  - Epidemiologic characteristics of pityriasis rosea in Athens Greece.

PMID- 16638394
TI  - High prevalence of hypothyroidism in male patients with cutaneous melanoma.
AB  - A recent study reported a higher than expected prevalence of hypothyroidism among
      patients with cutaneous melanoma. To further characterize and validate those
      findings, we conducted a retrospective review of the prevalence of hypothyroidism
      among all consecutive patients diagnosed with cutaneous melanoma in the
      dermatology clinic at the Michael E. DeBakey VA Medical Center (VAMC) in Houston,
      Texas. To accomplish this task, the electronic medical records of all patients
      diagnosed with cutaneous melanoma at the VAMC from January 2001 through October
      2004 were examined for signs of hypothyroidism. Data regarding the site of
      melanoma and age at diagnosis were obtained for these hypothyroid cases and for
      age- and gender-matched euthyroid controls from the same melanoma cohort. Among
      156 cutaneous melanoma patients (151 male and 5 female), 8 (5.1 %) showed a
      history of hypothyroidism [7 of 151 male (4.6 %) and 1 of 5 female (20 %)]. The
      prevalence of hypothyroidism among the male melanoma patients was significantly
      higher than that reported for the general population. The prevalence data
      concerning hypothyroidism among our female patients was not considered evaluable
      due to the primarily male distribution of our study population. We conclude that
      hypothyroidism (excluding iatrogenic etiologies) is frequent among male patients
      with cutaneous melanoma. Our results further suggest that a subset of melanoma
      tumors may respond to hormones of the hypothalamus-pituitary-thyroid axis,
      raising many questions that could influence the diagnosis, care, and treatment of
      a subset of melanoma patients.

PMID- 16638395
TI  - Association between solitary keratoacanthoma and cigarette smoking: a case
      control study.
AB  - Solitary keratoacanthoma (KA) is a common benign epithelial tumor of the skin
      characterized by rapid growth and a tendency toward spontaneous regression. The
      exact etiology and classification of KA are a matter of debate. Smokers also seem
      to be more affected than persons who never smoke. The objective of this study was
      to evaluate the association between solitary KA and smoking habit. A case-control
      study involving 78 patients diagnosed with KA and 199 controls from the related
      community was performed to evaluate the association between cigarette smoking and
      KA. A higher smoking prevalence was noted in cases (69.2 %) than controls (21.6
      %) and the odds ratio adjusted for sex and age was 9.1 (95 % CI 4.9 to 17.1, p<
      0.01). The mean tumoral diameter at surgery and the site of involvement was not
      statistically related to smoking. These findings suggest that cigarette smoking
      is associated with the development of KA.

PMID- 16638396
TI  - Carbon dioxide laser for the treatment of lupoid cutaneous leishmaniasis (LCL): a
      case series of 24 patients.
AB  - We report the use of a carbon dioxide laser to vaporize local cutaneous
      leishmaniasis. We used CO2 laser for the treatment of 24 patients with lupoid
      cutaneous leishmaniasis in Isfahan. We identified 24 patients with lupoid
      cutaneous leishmaniasis (LCL) for evaluation. All of the patients had clinical
      signs of LCL and had the lesion for more than 1 year. LCL diagnosis was confirmed
      by both direct smear and biopsy. The efficacy of laser was determined on the
      basis of cure and lack of relapse after 1 year. Treatment was performed using a
      CO2 laser (Lasersonic LS500 machine). The maximum power was 100 Watts and the
      pulse width was 0.5-5 seconds. There were 21 patients, 13 females and 8 males,
      who were treated and followed for 1 year. Mean duration of the lesions was 4.1+/-
      3.9 years. The treatment was well tolerated and complications were minimal, and
      included pain, xerosis, and mild erythema. Of these patients, 19 were disease
      free (90.47 % efficacy based on clinic and laboratory). Only 2 patients were
      treatment failures (9.5 %). Our results indicate that CO2 laser radiation is
      highly effective for treatment of lupoid cutaneous leishmaniasis.

PMID- 16638397
TI  - Adalimumab-induced urticaria.

PMID- 16638398
TI  - Three cousins with chronic foot ulcers from late-onset hereditary sensory and
      autonomic neuropathies type 2 (HSAN2).
AB  - The hereditary sensory and autonomic neuropathies (HSAN) are a group of rare
      disorders characterized by prominent sensory and autonomic neuropathy without
      motor involvement. We report three male cousins with chronic foot ulcers, all
      were affected with late-onset HSAN type 2 (HSAN2). In view of the history of
      consanguinity and male sex, X-linked recessive transmission was likely in our
      patients. According to the authors' knowledge this is the first report of HSAN2
      from Iran.

PMID- 16638399
TI  - Lipedematous alopecia of the scalp.
AB  - Lipedematous scalp is a rare disorder, mainly described in adult African-American
      females. We report 2 adult caucasian males with lipedematous scalp associated
      with androgenetic alopecia. Patients were studied by dermoscopy and
      histopathology; they were treated with finasteride 1 mg. In our patients,
      lipedematous scalp affected the occipital and the vertex areas and pathologically
      exhibited mild edema and thickening of the adipose subcutaneous layer. At
      videodermoscopy, lipedematous scalp areas showed linear areas of teleangiectasia
      within the scalp creases, possibly caused by compression of the superficial blood
      capillaries by the increased volume of the subcutaneous fat layer within the
      thickened scalp. Finasteride at a dose of 1 mg per day for 1 year induced mild
      improvement of androgenetic alopecia in one patient and stabilization of the
      disease in the other. The lipedematous scalps remain unchanged. Lipedematous
      scalp is apparently a rare disease even though the condition is probably
      underdiagnosed. As a matter of fact, we diagnosed lipedematous scalp in our
      patients during a clinical examination for androgenetic alopecia, which was the
      patients' complaint. The association of lipedematous scalp and androgenetic
      alopecia in our two patients appears to be coincidental.

PMID- 16638400
TI  - Pimecrolimus 1 percent cream in the treatment of psoriasis in a child.
AB  - Psoriasis is a chronic inflammatory skin disorder of multifactorial etiology.
      Because of the potential side effects of repeated topical application of potent
      corticosteroids, equally-effective, safer therapeutic options are required,
      especially in the treatment of children. We report on the efficacy of twice daily
      application of pimecrolimus 1 percent cream in a girl who suffered from psoriasis
      involving the eyelids and anogenital region. After 20 days of application of
      pimecrolimus cream the plaques completely resolved. No significant side effects
      have been observed. Topical pimecrolimus appears to be an effective and safe
      treatment for children with psoriasis. Our case observations provide further
      evidence for the beneficial effects of topical pimecrolimus in the treatment of
      psoriasis. Vehicle-controlled studies on a larger number of patients are now
      needed to investigate long-term efficacy and safety of topical pimecrolimus in
      the treatments of a variety of types of psoriasis in children.

PMID- 16638401
TI  - Penile pyoderma gangrenosum.
AB  - We present a case of penile pyoderma gangrenosum (PG) that responded dramatically
      to an 8-week course of prednisone and has not recurred over a 6-month period.
      Although quite uncommon, penile PG should be a diagnostic consideration in any
      patient with non-healing ulcerative lesions of the penis. A correct diagnosis in
      this situation precludes unnecessary or harmful therapeutic interventions and
      leads to proper management.

PMID- 16638402
TI  - Palmar hyperhidrosis. Safety efficacy of two anaesthetic techniques for botulinum
      toxin therapy.

PMID- 16638403
TI  - Treatment of disseminated facial warts through contact immunotherapy with
      diphenylcyclopropenone (DPCP).
AB  - This paper highlights the effect of diphenylcyclopropenone (DPCP) sensitization
      on warts resistant to other treatments and is interesting in views of the fact
      that all the facial warts apparently responded. To analyze the efficacy and side
      effects of DPCP treatment of viral warts, a prospective study was designed to
      follow six patients with chronic and resistant facial warts through immunotherapy
      sensitization with diphenylcyclopropenone for 10 weekly sessions. Patients were
      first sensitized with 2 percent DPCP and then followed by weekly maintenance of
      0.001-1 percent DPCP in acetone on facial warts until mild contact dermatitis was
      obtained. After application of DPCP to the warts of the face, all of the facial
      warts became inflamed and resolved. DPCP appears to be a valuable, safe, and well
      tolerated treatment for resistant and chronic facial warts.

PMID- 16638404
TI  - Cutaneous larva migrans in an unusual site.

PMID- 16638405
TI  - Koebner phenomenon in xanthelasma after treatment with trichloroacetic acid.
AB  - A 47-year-old woman presented with a history of yellow plaques on her eyelids.
      These lesions had been diagnosed clinically as xanthelasma and treated five times
      with topical applications of trichloroacetic acid (TCA) 33 percent. Despite
      flattening of the original lesions, the patient noticed extension of the lesions
      on the site of treatment following each session. Skin biopsy showed
      characteristic findings of xanthelasma. It appears that, in rare instances,
      xanthelasma palpebrarum may progress following TCA application by a Koebner-like
      phenomenon.

PMID- 16638406
TI  - Pulmonary embolism and deep jugular venous thrombosis resulting from compression
      by a lipoma.
AB  - Lipomas usually extend in subcutaneous tissues and rarely may be compressive. We
      report a case of neck lipoma resulting in jugular vein thrombosis and pulmonary
      embolism in a patient treated by clozapine. Clozpine may be considered an
      associated risk factor for thrombosis. This case suggests that performing a
      regional evaluation may be particularly important when thrombophlebitis occurs.

PMID- 16638407
TI  - Persistent periorbital edema as a sole manifestation of cutaneous lupus
      erythematosus: report of two cases.
AB  - In lupus erythematosus, dramatic periorbital edema and erythema without any
      evidence of other significant cutaneous or systemic involvement is unusual. We
      describe two patients with severe periorbital edema and erythema as the sole
      manifestation of cutaneous lupus erythematosus.

PMID- 16638408
TI  - Familial yellow nail syndrome.
AB  - A 70-year-old woman with yellow nail syndrome and right-sided pleural effusion,
      lower extremity edema, and hypoalbuminemia was followed for 18 months. She
      reported an 8-year history of asthma. She had four children (3 boys and 1 girl).
      Dystrophy, changes in color and shape of nails both hands and foot, along with
      lower extremity edema was observed in the daughter and two of her sons. One son
      had asthma. The patient reported that her grandmother had similar nail
      abnormality and lower extremity edema. Other family members and patient's
      grandchildren were healthy. This report demonstrates a case of familial yellow
      nail syndrome.

PMID- 16638409
TI  - Management of skin ulcers in a patient with mycosis fungoides.
AB  - We present a patient with a cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF)
      followed for more than 10 years. After several different aggressive treatments to
      control progression of CTCL/MF, the patient developed several ulcerated tumors on
      the abdomen and limbs. Specific systemic antibiotic therapy failed to treat skin
      infection. While treating the stage III CTCL with polychemotherapy, we used an
      active colloidal hydrogel topically to manage wound healing and to treat and
      prevent potential sources of sepsis. After 11 weeks of treatment we observed
      complete cicatrization of ulcerated tumors. We reported on this case to describe
      the importance of a correct management of skin ulcers in immunosuppressed
      patients in order to avoid possible systemic spread of infection which represents
      the major cause of death in these patients.

PMID- 16638410
TI  - Linear lichen planus and hepatitis C.
AB  - A 23-year-old man with hepatitis C was observed with brownish dome-shaped papules
      in a linear pattern on the chest. The papules were determined clinically and
      pathologically to be linear lichen planus. These lesions appeared during an
      interferon-alpha therapy for his hepatitis and resolved after topical treatment
      with tacrolimus ointment. Linear lichen planus and hepatitis C have been reported
      only twice previously. The association between these disorders and the potential
      role of interferon therapy are discussed.

PMID- 16638411
TI  - Keratoacanthoma centrifugum marginatum arising in vitiligo: a case report.
AB  - Keratoacanthoma centrifugam marginatum (KCM) is a rare variant of the
      Keratoacanthoma (KA) form of squamous cell carcinoma with only 30 cases reported
      to date. We report a case of KCM arising in a long-standing vitiligo lesion
      chronically exposed to sunlight. Over years, the vitiligo lesions gradually
      evolved into sclerotic plaques and subsequently KCM developed in one of the
      plaques.

PMID- 16638412
TI  - Acquired eyelash trichomegaly and generalized hypertrichosis associated with
      breast anomaly.
AB  - Acquired eyelash trichomegaly is a rare condition. We present a 23-year-old woman
      with acquired trichomegaly and generalized hypertrichosis from childhood. The
      patient also exhibited bilateral nipple retraction and unilateral left-sided
      accessory nipple. According to our knowledge the association between
      trichomegaly, hypertrichosis, and breast anomaly has not been reported.

PMID- 16638413
TI  - Actinomycosis presenting as a large facial mass.

PMID- 16638414
TI  - Guillain-Barre syndrome-like presentation in borderline leprosy with type-2
      reaction.
AB  - A 46-year-old man with borderline lepromatous leprosy with type-2 reaction being
      treated with multi-bacilliary-multiple drug therapy and steroids presented with
      an acute onset of flaccid quadriparesis. A nerve conduction study and CSF
      analysis were similar to that seen in Guillain Barre syndrome. Muscle weakness
      improved considerably with an increased dose of corticosteroid; after 6 months
      the patient recovered completely.

PMID- 16638415
TI  - Results of a randomized open-label crossover study of the bioequivalence of
      subcutaneous versus intramuscular administration of alefacept.
AB  - Alefacept selectively reduces memory T cells and inhibits T-cell activation.
      Large randomized trials have shown that intramuscular (IM) delivery of alefacept
      is safe and effective in treating plaque psoriasis. Subcutaneous (SC)
      administration of alefacept may provide advantages for some patients including
      convenience, ease of use, and reduced pain on injection. We conducted a
      randomized, open-label, crossover study in 50 healthy volunteers to determine if
      alefacept 15 mg administered SC is bioequivalent to alefacept 15 mg administered
      IM. The pharmacokinetic parameters used to determine bioequivalence were area
      under the serum concentration-time curve to the last measurable value (AUClast;
      primary endpoint), peak serum concentration (Cmax), and AUC to infinity
      (AUCinfinity). For each of these parameters, the 90 percent confidence intervals
      for the least squares mean ratios of alefacept SC to alefacept IM were well
      within the conventional bioequivalence range of 80 percent to 125 percent. These
      data, together with the finding that the mean serum concentration-time curves for
      alefacept were nearly identical following both routes of administration,
      demonstrate the bioequivalence of alefacept SC and alefacept IM. No clinically
      important differences between the pharmacodynamic profiles (total lymphocyte and
      lymphocyte subset counts) of the two routes of administration were observed.
      Alefacept SC and alefacept IM were similarly well tolerated. Our results suggest
      that SC dosing may represent a viable delivery option for alefacept.

PMID- 16638416
TI  - Role of slit skin smear examination in cutaneous T-cell lymphomas and other
      chronic dermatoses.
AB  - The purpose of this study was to evaluate the utility of slit-skin smear
      examination in the diagnosis of various chronic dermatoses. The study included 24
      patients with chronic dermatoses who presented to the skin outpatient department.
      Ten patients had idiopathic erythroderma, seven were diagnosed with airborne
      contact dermatitis, four had cutaneous T-cell lymphoma, two had chronic actinic
      dermatoses, and a single patient had panniculitis. Slit skin smears were obtained
      from all patients, stained with Leishman stain, and examined under microscope.
      Out of 24 patients, all four cases of cutaneous T-cell lymphoma showed abnormal
      cells suggestive of lymphomatous infiltration, two patients with airborne contact
      dermatitis showed reactive lymphocytes, and two idiopathic erythroderma cases
      showed numerous eosinophils in the smear. Slit skin smear examination is a simple
      rapid, decisive test in the diagnosis of cutaneous T-cell lymphoma. It is a
      useful screening test, especially in Sezary syndrome and diseases with specific
      skin infiltrate.

PMID- 16638417
TI  - Atopic dermatitis and systemic autoimmune diseases: a descriptive cross sectional
      study.
AB  - Atopic dermatitis (AD) has a Th2 (T-helper 2) immune-reactivity pattern. However,
      the majority of systemic autoimmune diseases, such as rheumatoid arthritis,
      multiple sclerosis, and insulin dependent diabetes mellitus show a Th1 (T-helper
      1) reactivity pattern. From this, one may hypothesize that AD and the Th1
      autoimmune diseases could be inversely associated and AD may be more common in
      the minority of autoimmune diseases with a Th2 overactivity pattern such as
      systemic lupus erythematosus. A cross sectional study was designed. Our patients
      were enrolled from a general university hospital (all systemic autoimmune
      patients in every medical ward based on definite diagnoses in their medical
      records). Information on atopic dermatitis was obtained by questionnaires and
      physical examination by a dermatologist. A total of 63 patients were studied;
      17.5 percent of cases had atopic dermatitis in the past or present. There were 31
      patients 49.2 %) who carried a diagnosis known to be associated with Th1
      reaction, and 21 patients (33.3 %) who had a disease associated with Th2-type
      reactivity. In 11 patients (17.5 %) the T-cell reaction type was not definitively
      classified. The relative frequency of AD was 9.7 percent (3 of 31 cases) in Th1
      related autoimmune diseases, 28.6 percent (6 of 21 cases) in Th2-related
      autoimmune diseases and 18.2 percent (2 of 11 cases) in the unclassified
      category, a difference not statistically significant. Although the power of this
      study is not high enough to show a statistical significance, AD seems to be
      uncommon in patients with autoimmune diseases associated with Th1 overactivity.

PMID- 16638418
TI  - Role of apoptosis stimulus factor and its ligand in the induction of apoptosis in
      some ultraviolet induced diseases.
AB  - BACKGROUND: Fas (factor of apoptosis stimulus) is one of the death receptors
      belonging to the tumor necrosis factor superfamily of receptors. When bound to
      its ligand, Fas-ligand (Fas-L), it triggers apoptosis. Ultraviolet (UV) rays can
      induce keratinocyte apoptosis by Fas/Fas-L interaction. AIM: The aim of the study
      was to evaluate the role of Fas and Fas-L in basal cell carcinoma (BCC) as an
      example of malignant neoplasm and discoid lupus erythematosus (DLE) as a benign
      skin disease, which are both induced by UV. SUBJECTS AND METHODS: The study
      included 20 cases of BCC, 20 cases of DLE and ten control cases. All biopsies of
      BCC and DLE were examined histopathologically. They were also examined for Fas
      and Fas-L by PCR. RESULTS: In BCC, apoptosis was detected in 60 percent of cases.
      Fas was found to be positive in only one case and it was found to be negative in
      the other 19 cases (95 %). Fas-L was found to be positive in 100 percent of
      cases. In DLE, apoptosis was detected in 90 percent of cases. Fas was positive in
      80 percent of cases, Fas-L was positive in 90% of cases. CONCLUSION: Over
      expression of Fas-L and lack of expression of Fas by tumor cells together with
      other factors act in favor of BCC by helping its survival and progression. Also,
      it seems that Fas/Fas-L interaction plays a critical role in the apoptosis seen
      in cases of DLE and hence in the pathogenesis of DLE.

PMID- 16638419
TI  - An evidence-based review of medical and surgical treatments of genital warts.
AB  - Genital human papillomavirus (HPV) infection is the most common sexually
      transmitted disease. Each year 1 million new cases of genital warts are
      diagnosed, two thirds of which are in women. The estimated prevalence rate in the
      US population is 15 percent. HPV infects keratinocytes. Such infection can
      manifest clinically as warts. Treatment options for genital warts are numerous,
      well established, and effective. Topical treatments include podophyllin resin,
      imiquimod, trichloroacetic acid, and podophyllotoxin. Surgical or destructive
      therapies include carbon dioxide laser, surgical excision, loop excision,
      cryotherapy, and electrodessication. Interferon can be injected locally or
      administered systemically to treat genital warts. Evidence of efficacy in the
      treatment of genital warts is drawn from randomized blind-controlled trials,
      prospective studies, and retrospective cohort studies. Evidence of efficacy
      appears to be good, but more head-to-head studies and comparisons of combination
      therapies versus monotherapy need to be done. Treatment of choice depends on the
      number, size, and location of lesions. There is little certainty that any
      approach is more effective than another, however costs differ. It would seem that
      the first line destructive treatment is cryotherapy, but surgery and
      electrodesiccation are more effective. The first line topical treatments appear
      to be podophyllotoxin and imiquimod. Interferon is too expensive and
      trichloracetic acid is too inconsistent to be recommended as primary treatment.
      It is unclear if combinations of therapies are more effective than monotherapy.
      Side effect profile, cost, effectiveness and convenience (ability to attend
      physician's office or to undertake protracted home treatment) define the choice
      of therapy.

PMID- 16638420
TI  - Severe atopic dermatitis and leflunomide: first clinical experience and
      highlights of pertinent experimental data.
AB  - Atopic dermatitis is a common chronically relapsing disease affecting about 10
      percent of children and 3 percent of adults. Currently, no standard management
      exists for long-term treatment. Topical corticosteroids and recently calcineurin
      inhibitors are effective in most patients. In severe cases, however, systemic
      agents have to be employed. Their use may be limited by unwanted effects or
      insufficient long-term efficiency. Leflunomide is an immunomodulating and disease
      modifying antirheumatic drug with anti-inflammatory and immunosuppressive
      activity, exhibiting an extremely long in vivo half life. Because T cells and
      eosinophils play an important role in the pathophysiology of atopic dermatitis,
      and long-term treatment is often required, leflunomide seems to be ideally suited
      for treatment of severe atopic eczema. We present a case highlighting the
      application regimen of leflunomide, and discuss the pathophysiological mechanism
      of action in atopic dermatitis. Because treatment benefit differs between
      patients, we propose the design of a proof-of-principle study for leflunomide in
      atopic dermatitis encompassing an evaluation of predictive markers for successful
      application.

PMID- 16638421
TI  - Nephrogenic fibrosing dermopathy: case report and review.

PMID- 16638422
TI  - Palm devices in dermatology.

PMID- 16638423
TI  - Lymphomatoid papulosis localized to the face.
AB  - We report a case of lymphomatoid papulosis (LyP) localized to the face. Only ten
      cases of localized LyP have been reported, and those involved the extremities.
      Three of those cases finally evolved to classic LyP with a widespread
      distribution of the lesions, the other cases remain limited. The evolution into
      lymphoma for the localized form appears to be equivalent to that reported with
      the generalized LyP (20 %), underlining the need for long-term followup of these
      patients. This is the first reported case of LyP localized to the face.

PMID- 16638424
TI  - Treatment of invasive squamous cell carcinoma with 5-percent imiquimod cream.
AB  - Skin cancer is a major problem in the elderly. Squamous cell carcinoma (SCC), the
      second most common skin cancer, typically occurs in this age group. Despite a
      number of modalities readily available for treatment (depending on the tumor
      site, and depth of invasion) there remains the problem of individuals with
      multiple lesions who may be unsuitable for existing treatments for SCC,
      particularly surgery. Consequently, the search for novel treatments continues. To
      our knowledge, there are only 6 published reports of invasive SCC treated with 5
      percent imiquimod cream.

PMID- 16638425
TI  - Childhood cutaneous tuberculosis: a 20-year retrospective study in Tunis.
AB  - Despite prevention programs, tuberculosis is still endemic in developing
      countries. We assessed the epidemiologic and clinical profiles of childhood
      cutaneous tuberculosis in our dermatology department from 1981 to 2000 and
      compared it to previous Tunisian reports and to the relevant literature. This is
      a retrospective study over a 20-year period (1981-2000) in a large teaching
      hospital of the capital. Patients included were below age 15 years. Diagnosis was
      based upon clinical examination, tuberculin reaction, histopathology and response
      to antitubercular therapy. There were 26 patients with cutaneous tuberculosis,
      0.1 percent of the total number of dermatology outpatients for that time period.
      Of these 26, seven (27 %) were immunocompetent. There were four boys and three
      girls and the mean age was 9.5 years. Three patients had lupus vulgaris, three
      had scrofuloderma, and one child had orificial tuberculosis. Six out of seven
      children were BCG vaccinated. There was no family history of tuberculosis. The
      Mantoux reaction was positive in six children. There was no systemic organ
      involvement in all cases. All patients were treated successfully with triple or
      quadruple anti-tubercular drugs for 4-11 months. Compared to a previous Tunisian
      report conducted over an 8-year period in the seventies, the incidence of
      childhood cutaneous tuberculosis has decreased. In that report, scrofuloderma was
      the most frequent form. Currently the incidence of lupus vulgaris has reached
      that of scrofuloderma, demonstrating the increase of the clinical pattern
      associated with strong immunity. All children had localized disease and responded
      to antimycobcterial chemotherapy.

PMID- 16638426
TI  - Necrotic erythema nodosum leprosum.
AB  - A 32-year-old fisherman suffering from lepromatous leprosy presented with fever,
      joint pains, bullous lesions, and multiple well-defined ulcers on the extremities
      and back of 10-days duration. The bullae ruptured to form ulcers of varying sizes
      with well-defined margins and necrotic bases. A few of the ulcers had black
      crusts resembling eschars. An immunofluorescence study ruled out autoimmune
      bullous disease. Histopathology of a lesion showed features of erythema nodosum
      leprosum.

PMID- 16638427
TI  - Leukemia cutis resembling a flare-up of psoriasis.
AB  - Leukemia cutis represents a skin infiltration by leukemic cells. Clinically it
      can mimic a wide variety of dermatoses. We describe the case of a 64-year-old man
      with psoriasis who presented with a 4-day history of erythematous, slightly
      scaly, asymptomatic plaques distributed on the trunk and upper-extremities, and
      associated asthenia, myalgias, and anorexia. A skin biopsy revealed a leukemic
      infiltrate. Studies of peripheral blood and bone marrow provided a diagnosis of
      acute monocytic leukemia. This case report shows the importance of the clinical
      suspicion for the diagnosis of leukemia.

PMID- 16638428
TI  - Clinico-epidemiologic study of cutaneous leishmaniasis in Diyarbakir Turkey.
AB  - Cutaneous leishmaniasis (CL) is a zoonotic disease, endemic and notifiable in
      southeastern Turkey. We investigated clinical features, individual
      characteristics, and environmental factors of affected patients, and identified
      additional patients with CL in Diyarbakir. In 2002 we studied the epidemiology of
      CL in Dedekoy and Durabeyli towns in Diyarbakir Province. We evaluated patients
      with any skin lesions. A questionnaire including demographic details was
      completed by each patient. Clinical details of lesions and other dermatological
      findings were recorded. We walked around the town and surveyed it for
      environmental factors. CL was diagnosed in 78 individuals aged 1-85 years (mean
      age of 20). Although all age groups were affected, the majority of patients were
      under age 20. The lesions ranged from approximately 0.5 to 20 cm. They were
      located on the face (46.7 %), upper extremity (23.2 %), lower extremity (5.1 %),
      and other sites. Different types of lesions were observed such as nodule with
      crust, nodule with osseous crust, violaceous infiltrative plaque with vegetative
      nodule, erysipelas-like plaque verrucous annular plaque, and eczema-like plaques.
      The incidence of CL is increasing in Dicle and Durabeyli towns and the clinical
      appearance may vary greatly.

PMID- 16638429
TI  - Generalized B-cell non Hodgkin's lymphoma in association with leukocytoclastic
      vasculitis and disseminated intravascular coagulation.
AB  - A 66-year-old woman was referred a 4-month history of asthenia, weight loss,
      productive cough, increasing dyspnea, epigastric pain, and night sweats. A B-cell
      non-Hodgkin lymphoma was discovered in association with a severe leukocytoclastic
      vasculitis and disseminated intravascular coagulation. The patient was treated
      successfully with the combination of cyclophosphamide, vincristine, prednisone,
      and rituximab.

PMID- 16638430
TI  - Familial reticulate acropigmentation of Dohi: a case report.
AB  - Reticulate acropigmentation of Dohi is a rare dyschromic disorder occurring
      predominantly among Japanese individuals. Only a few similar cases from Europe
      and some parts of Asia have been reported. This report describes two Filipino
      siblings who had reticulate hyperpigmented and hypopigmented macules on the
      extremities, typical of the disorder.

PMID- 16638431
TI  - Bilateral localized lipoatrophy secondary to a single intramuscular
      corticosteroid injection.
AB  - A 15-year-old boy developed two, almost symmetric, asymptomatic, depressed
      plaques, localized to both buttocks after receiving a single intramuscular
      corticosteroid injection in his right buttock for treatment of lumbar pain. He
      suffered from asthma since early childhood, and had been repeatedly treated with
      corticosteroid injections for many years as a young child. A skin biopsy from
      both lesions was performed, showing a decrease in the number and size of
      adipocytes. We describe a case of acquired localized lipoatrophy with a
      particular bilateral distribution secondary to a single intramuscular
      corticosteroid injection.

PMID- 16638432
TI  - Atypical cutaneous leishmaniasis resembling eczema on the foot.
AB  - Cutaneous leishmaniasis (CL) typically presents as ulcerated or crusted nodules
      and plaques. Eczematous morphology of CL lesions is unusual. We report a case of
      CL that presented as a large eczematous plaque with no clinically obvious primary
      lesion.

PMID- 16638433
TI  - Normolipemic papular xanthoma with xanthelasma.
AB  - Xanthomas are a common presentation of disorders of lipid metabolism, usually
      associated with abnormalities of cholesterol metabolism. A 35-year-old woman
      presented to us with the lesions of xanthelasma on the upper eyelids and papular
      xanthomas on the rest of the body. Routine investigations and systemic
      examination were normal. The lipid profile was within normal range and serum
      protein electrophoresis showed normal pattern. Histopathology from a papular
      lesion showed foamy histiocytes with Touton giant cells. We present a case of
      normolipemic papular xanthoma with xanthelasma, a very rare occurrence.

PMID- 16638434
TI  - Secondary syphilis clinically mimicking pseudolymphoma of the face.
AB  - Syphilis has been given titles such as the great imitator, the great mimic, and
      the great masquerader. It may lack pathognomonic signs and often presents similar
      to many other dermatological conditions. We present a case of a young woman who
      developed asymptomatic papulonodular lesions on the forehead; the lesions were
      clinically similar to pseudolymphoma but it was determined that she had secondary
      syphilis exhibiting prozone phenomenon. She also had alopecia of eyebrows. Both
      the alopecia as well as nodular lesions clinically resembling pseudolymphoma
      responded to and completely recovered with antisyphilitic treatment.

PMID- 16638435
TI  - Waardenburg syndrome type 1.
AB  - Waardenburg syndrome (WS) is a rare disease characterized by sensorineural
      deafness in association with pigmentary anomalies and defects of neural-crest
      derived tissues. Depending on additional symptoms, WS is classified into four
      types, WS1, WS2, WS3 and WS4. WS1 and WS3 are attributed to mutations in PAX3,
      whereas WS2 is heterogeneous, being caused by mutations in the microphthalmia
      associated transcription factor gene in some but not all affected families. WS4
      is attributed to mutations in the endothelin-3 or the endothelin-B receptor genes
      and SOX10 gene. WS1 is an auditory-pigmentary disorder comprising sensorineural
      hearing loss and pigmentary disturbances of the iris, hair, and skin, along with
      dystopia canthorum. We report a case with a confirmed diagnosis of WS1 and review
      the relevant literature for this rare disorder.

PMID- 16638436
TI  - Pyogenic granuloma on the hand subsequent to friction blister in a hand surgeon.
AB  - A case of pyogenic granuloma in a 62-year-old hand surgeon secondary to friction
      blister is reported. He developed a fast growing, hypertrophic inflammatory
      papule consisting of exceptionally richly vascularized granular tissue. This
      dusky red lesion was located on the thenar part of the hand. We find no prior
      report of PG attributed to friction blister.

PMID- 16638437
TI  - Urticaria and lip fasciculation may be prodromal signs of brain malignancy.
AB  - The association of urticaria and cancer usually is seen with lymphoreticular
      system malignancies. Recalcitrant intra-nostril pruritus has been associated with
      fourth-ventricle tumors of the brain. Rarely, urticaria has been described with
      cancer of the lung, usually small-cell adenocarcinoma. We describe a girl who
      suffered with chronic urticaria for 3 months before lip fasciculation began to be
      observed. CT scan revealed a brain tumor adjacent to the cerebellum, which was
      diagnosed as astrocytoma grade II. Because of the location, the tumor was not
      operable, but after one course of radiotherapy, both the urticaria and lip
      fasciculation disappeared.

PMID- 16638438
TI  - Solitary plasmocytoma of frontal bone presenting as an asymptomatic forehead
      lump.
AB  - Solitary plasmocytoma of bone is a rare type of plasma cell tumor. We present a
      case of a solitary extramedullary plasmacytoma of the frontal bone presenting as
      an asymptomatic forehead lump with clinically benign characteristics. This case
      highlights the need for a high index of suspicion when dealing with enlarging
      subcutaneous lumps of the forehead and scalp. The significance of this lies in
      the appropriate sequencing of investigations and the implementation of the
      necessary treatment regimen.

PMID- 16638439
TI  - Intralesional bleomycin as alternative therapy in the treatment of multiple basal
      cell carcinomas.
AB  - An 82-year-old female with with multiple basal cell carcinomas is presented. Her
      history includes treatment for similar lesions for 15 years with surgical and X
      ray methods. We injected intralesional bleomycin to eight new histologically
      proven basal cell cancers. A followup at 2 years demonstrates the effectiveness
      of this therapy.

PMID- 16638440
TI  - The efficacy of topical cyproterone acetate alcohol lotion versus placebo in the
      treatment of the mild to moderate acne vulgaris: a double blind study.
AB  - Acne is an inflammatory condition of the pilosebaceous unit. One of the essential
      factors for development of acne lesions is increased sebum excretion that is
      promoted by androgen. It is shown that oral cyproterone acetate significantly
      reduces the sebum excretion. In this study we evaluated the efficacy of
      cyproterone acetate alcohol lotion (CAAL) in the treatment of the mild to
      moderate acne vulgaris. This was a randomized double-blind clinical trial
      performed on 86 female patients with mild to moderate acne. They were randomly
      divided into 3 groups and were treated with 0.5 percent CAAL (n = 30), 1 percent
      CAAL (n = 13) and placebo (n = 43). They were followed every 15 days for a period
      of 45 days. Response to treatment was evaluated by the total acne lesions
      counting (TLC) and acne severity index (ASI) and was analyzed statistically by
      SPSS program. The efficacy of treatment on TLC was maximum for 1 percent CAAL (90
      % reduction in TLC)(P value = 0.000). CAAL at 0.5 percent was able to reduce TLC
      as high as 80.8 percent during 6 weeks followup. The efficacy of placebo was
      determined to be 38.5 percent. Regarding TLC, 1 percent CAAL was 2.33 times more
      effective than placebo. CAAL at 0.5 percent was 2.09 times more effective than
      placebo in this respect. The efficacy of treatment on ASI was maximum for 1
      percent CAAL (88 % reduction in ASI)(P value = 0.000). CAAL at 0.5 percent
      reduced ASI as much as 79.5 percent during 6 weeks of followup. The efficacy of
      placebo was calculated to be 9.8 percent in reduction of ASI . Regarding ASI, 1
      percent CAAL was 8.97 times more effective than placebo. CAAL at 0.5 percent was
      8.06 times more effective than placebo. Regarding the results of this study, we
      suggest the use of cyproterone acetate alcohol lotion as one of the main
      treatments for mild-moderate acne in female patients and as an adjuvant treatment
      for moderate to severe acne vulgaris.

PMID- 16638441
TI  - Missense mutations in the coagulation factor XII (Hageman factor) gene in
      hereditary angioedema with normal C1 inhibitor.
AB  - Hereditary angioedema is characterized by recurrent skin swelling, abdominal pain
      attacks, and potentially life-threatening upper airway obstruction. The two
      classic types are both caused by mutations within the complement C1 inhibitor
      gene. A recently described new type does not show a deficiency of C1 inhibitor
      and affects almost exclusively women. We screened twenty unrelated index patients
      with this new type of hereditary angioedema for mutations in the coagulation
      factor XII gene. Two different missense mutations were identified in exactly the
      same position within exon 9 of the F12 gene. 'Mutation 1' (1032C-->A),
      encountered in five patients, predicts a threonine-to-lysine substitution
      (Thr309Lys). 'Mutation 2' (1032C-->G), observed in one patient, results in a
      threonine-to-arginine substitution (Thr309Arg). The predicted structural and
      functional impact of the mutations, their absence in 145 healthy controls, and
      their co-segregation with the phenotype in five families provide strong support
      that they cause disease.

PMID- 16638443
TI  - Growth and development of the child's hip.
AB  - The child's hip begins in intrauterine development as a condensation of mesoderm
      in the lower limb bud that rapidly differentiates to resemble the adult hip by
      eight weeks of life. The developmental instructions are transmitted through
      complicated cell signaling pathways. From eight weeks of development to
      adolescence, further growth of the hip is focused on differentiation and the
      establishment of the adult arterial supply. The postnatal growth of the child's
      hip is a product of concurrent acetabular and proximal femoral growth from their
      corresponding growth plates. Absence of appropriate contact between acetabulum
      and proximal femur yields an incongruent joint. Multiple disease processes may be
      understood in light of this growth process, including Legg-Calve-Perthes disease
      and developmental dysplasia of the hip.

PMID- 16638444
TI  - Evaluation of the child who has hip pain.
AB  - Evaluation of children who have hip pain can be a diagnostic challenge. This
      article reviews pertinent history taking, physical examination, laboratory
      testing, and imaging studies that assist in reaching a correct diagnosis. It also
      reviews the diagnostic categories that are important in formulating a
      differential diagnosis to frame clinical decision making.

PMID- 16638445
TI  - Role of ultrasound in the diagnosis and management of developmental dysplasia of
      the hip: an international perspective.
AB  - Early diagnosis of developmental dysplasia of the hip is very important for
      proper treatment. Different ultrasound techniques have been used for early
      diagnosis of developmental dysplasia of the hip, but two of them are widely used
      in orthopedic practice: Graf's technique in Europe and Harcke's method in the
      United States. Our experience has led us to use an ultrasound technique that
      combines the two methods. Use of ultrasound has reduced the number of late
      presenting cases, shortened treatment time, and decreased the number of surgical
      procedures of the hip joint in Poland.

PMID- 16638446
TI  - Treatment of developmental dysplasia of the hip after walking age with open
      reduction, femoral shortening, and acetabular osteotomy.
AB  - The one-stage surgical treatment for developmental dysplasia of the hip
      consisting of open reduction, femoral shortening, and pelvic osteotomy-is a
      demanding procedure, one that is more challenging, technically, than a staged
      procedure. It can, however, be done safely and effectively, providing good
      conditions for proper development of the hip joint in the older child who has
      untreated developmental dysplasia of the hip.

PMID- 16638447
TI  - Treatment of late dysplasia with Ganz osteotomy.
AB  - Following careful study, the Ganz periacetabular osteotomy was introduced in 1988
      for the treatment of adolescent and adult hip dysplasia. It offers a powerful and
      versatile ability to reorient the acetabulum, restoring near-normal biomechanics,
      improving symptoms, and delaying or preventing osteoarthritis. This article
      outlines hip dysplasia and the biomechanical deficiencies, the assessment of
      patients who have hip dysplasia, and the technique of performing the osteotomy.
      The early and mid follow-up radiographic and clinical outcomes are reviewed and
      complications associated with the procedure are discussed.

PMID- 16638448
TI  - Operative reconstruction for septic arthritis of the hip.
AB  - The long-term effects of initial treatment for infantile septic arthritis of the
      hip differ and depend on patient age, infecting organism, and timing and adequacy
      of surgical and pharmacologic treatment. Appropriate and timely reconstructive
      operations benefit hip growth and development by providing the best possible hip
      joint mechanics at skeletal maturity. Any surgical treatment for severe sequelae,
      however, must be regarded as a measure that temporarily improves clinical
      function and delays the more definitive procedures that are reserved for adult
      patients. This article summarizes the surgical modalities currently available to
      reduce and stabilize a damaged femoral head and neck and to reconstruct femoral
      acetabular articulation.

PMID- 16638449
TI  - Evaluation and treatment of hip dysplasia in cerebral palsy.
AB  - Hip problems, including progressive subluxation, dislocation, and pain, are
      common in patients with cerebral palsy, particularly those who are nonambulatory
      with a large degree of spasticity. Clinical and radiographic screening
      facilitates early detection, and surgery is indicated to prevent progressive
      dysplasia. Although an early soft tissue release may prevent progressive
      subluxation in a subset of cases, bony reconstructive surgery is indicated for
      patients with established bony deformity. Salvage procedures are recommended to
      treat chronic pain caused by established subluxation or dislocation.

PMID- 16638450
TI  - Hip disorders in children who have spinal cord injury.
AB  - Little has been written regarding the assessment and treatment of hip disorders
      in children who have underlying paralysis. Each year approximately 2000 people
      younger than 20 years of age suffer a spinal cord injury (SCI). This compares
      with a larger number of children who have other forms of neurologic disorders,
      such as myelodysplasia, which affects approximately 6000 newborns annually in the
      United States, and for which there is a large body of literature describing the
      natural history and treatment of hip disorders in children who have
      myelodysplasia. This article focuses on hip disorders in children who have SCI,
      although there is clearly commonality in hip disorders that transcends many
      neurologic disorders.

PMID- 16638451
TI  - Evaluation and treatment of hip dysplasia in Charcot-Marie-Tooth disease.
AB  - The hip dysplasia seen in Charcot-Marie-Tooth disease is neuromuscular in nature.
      It usually presents in the second or third decade of life and is initially
      asymptomatic but may later present with pain and gait abnormalities. Treatment
      should be aimed at addressing the acetabular and femoral components of the
      dysplasia. Early recognition is essential to avoid serious morbidity associated
      with the condition.

PMID- 16638452
TI  - Controversies in slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder.
      This article reviews the major controversies in SCFE as of the year 2005. These
      are (1) treatment of the unstable SCFE, (2) the role of osteotomy in the
      treatment of SCFE, (3) prophylactic fixation of the contralateral hip in children
      presenting with unilateral SCFE, and (4) methods of fixation in the very young
      child with SCFE.

PMID- 16638453
TI  - Fractures of the hip in children.
AB  - Fractures of the hip are uncommon in children, and their importance is related
      not to the frequency of the injury but to the frequency of complications. Many of
      these complications can be minimized or avoided by anatomic reduction and
      internal fixation. Open reduction frequently is necessary to obtain a stable,
      anatomic reduction. Regardless of the age of the child, stable fixation of the
      fracture must be given priority over preservation of the proximal femoral physis.
      The development of osteonecrosis, however, is most likely related to the severity
      of the initial injury and is largely unaffected by treatment of the fracture.

PMID- 16638454
TI  - Hip arthroscopy in children and adolescents.
AB  - Hip arthroscopy has become an established procedure for certain indications in
      adults; however, experience in children and adolescents has been more limited.
      This article reviews the technique, indications, and results of hip arthroscopy
      in children and adolescents.

PMID- 16638456
TI  - Low-molecular-weight heparins in the treatment of cancer-associated thrombosis: a
      new standard of care?
AB  - Cancer patients are twice as likely to develop postoperative venous
      thromboembolism (VTE) than non-cancer patients undergoing the same surgical
      procedure. Causes of cancer-associated thrombosis include: the capacity of tumor
      cells and their products to interact with platelets, clotting, and fibrinolytic
      proteins. Aggressive antitumor therapy with agents such as platinum compounds,
      high-dose fluorouracil, mitomycin-C, tamoxifen, and growth factors increase the
      risk of cancer-associated thrombosis. Despite the high risk of VTE in patients
      with cancer, thromboprophylaxis in surgical and medical oncology patients is low.
      Initial therapy of VTE in patients with cancer is low-molecular-weight heparin
      (LMWH) or unfractionated heparin. Long-term secondary prophylaxis of VTE is
      generally accomplished with oral anticoagulants, primarily warfarin. Evidence
      supports the use of LMWH for prevention and treatment of cancer-associated
      thrombosis because it is more easily administered, does not require laboratory
      monitoring, has a lower risk of adverse events, and is more cost effective than
      unfractionated heparin. In addition, the antineoplastic effects of LMWH have been
      demonstrated, including direct antitumor, antiangiogenic, and immune system
      modulatory action. Each LMWH is a unique biological entity having product
      specific molecular and structural attributes; therefore, different LMWHs cannot
      be given interchangeably. Continued investigation of LMWH therapy in patients
      with cancer is warranted.

PMID- 16638457
TI  - The role of low-molecular-weight heparins as supportive care therapy in cancer
      associated thrombosis.
AB  - Venous thromboembolism (VTE) is a common complication of malignant disease,
      affecting approximately 1 in 200 cancer patients. Oncology nurses are
      instrumental in identifying patients with cancer at high risk of venous
      thromboembolism. Risk factors include: stage of disease, chemotherapy, the
      patient's degree of immobility, a history of recent surgery, and the presence of
      a central venous catheter. The treatment of venous thromboembolism in patients
      with cancer usually involves a sequential combination of unfractionated heparin
      or low-molecular-weight heparin (LMWH), followed by oral warfarin or LMWH. LMWHs
      are an alternative to warfarin for secondary prophylaxis and long-term treatment.
      LMWH is given by subcutaneous injection, does not require hospitalization for
      administration or routine laboratory monitoring. Recent clinical trial results
      have shown that LMWH use is associated with improved survival in cancer patients
      with relatively good prognoses. Patients receiving any anticoagulant therapy
      should be monitored for signs of pulmonary embolism or bleeding and intravenous
      sites (if present) should be monitored for oozing. Appropriate patient selection,
      a carefully constructed treatment plan, extensive patient education, and regular
      patient contact are integral elements for the nursing care of patients with
      cancer-associated thrombosis treated in the outpatient setting.

PMID- 16638458
TI  - Treatment of cancer-associated thrombosis: distinguishing among antithrombotic
      agents.
AB  - The risk of cancer-associated thrombosis can be substantial, depending on tumor
      type, extent of cancer, and type of treatment. Unfractionated heparin and
      warfarin have been used in the prevention of cancer-associated thrombosis, but
      low-molecular-weight heparin (LMWH) is widely used for the prevention of venous
      thromboembolism in high-risk patients. Long-term management with warfarin is
      associated with close monitoring, an increased risk of drug interactions, and
      bleeding. LMWHs may offer an alternative outpatient treatment strategy for
      prophylactic treatment because of their simpler dosing, more predictable
      anticoagulant activity, and improved safety profile. Clinical trials examining
      the treatment of venous thromboembolism with LMWH in patients with cancer suggest
      a survival advantage for the treated groups. Subtle differences in the
      pharmacokinetics of available LMWHs exist, and each LMWH should be regarded as a
      distinct drug. Pharmacists should be aware of the US Food and Drug Administration
      approved uses for each LMWH, dosing options, and the advantages and disadvantages
      of available delivery systems for various patient populations. Pharmacists can
      play a major role in educating patients and other health care professionals on
      risk factor recognition, patient risk stratification, and proper agent selection
      for prevention and treatment of cancer-associated thrombosis.

PMID- 16638459
TI  - Abdominal wall reconstruction.

PMID- 16638461
TI  - Structural and functional anatomy of the abdominal wall.
AB  - Multiple options exist for managing complex abdominal wall defects. These options
      range from the use of autologous tissue with rearrangement procedures to the use
      of prosthetic or bioprosthetic materials. All options rely on a thorough
      understanding of the structural and functional anatomy of the abdominal wall and
      the relationship of varying anatomical structures to provide the optimal
      reconstructive procedure. A successful reconstruction is achieved when the
      structural anatomy is integrated with understanding the dynamic function of the
      abdominal wall.

PMID- 16638462
TI  - The use of prosthetics in abdominal wall reconstruction.
AB  - Large ventral or incisional hernias are often difficult to manage. Most commonly
      patients are referred to reconstructive surgeons after multiple failed attempts
      of hernia repair. The use of prosthetic and bioprosthetic materials have aided
      greatly in the management of complex abdominal wall defects. A full understanding
      of the advantages and disadvantages of specific prosthetic materials available,
      and the associated complications of use, remains elusive, however. This article
      provides information concerning the applications of appropriate prosthetic
      material for temporary or permanent closure of difficult abdominal wall defects.

PMID- 16638463
TI  - The role of bioprosthetics in abdominal wall reconstruction.
AB  - In several common situations, bioprosthetic materials may have distinct
      advantages over synthetic mesh and autologous flap or graft techniques for
      abdominal wall reconstruction. These off-the-shelf materials entail no donor site
      morbidity and are used successfully in contaminated wounds owing to their ability
      to resist infection, become revascularized and incorporated into host tissue, and
      reduce visceral adhesions. Fibrovascular incorporation into surrounding tissues
      and implant remodeling reduce the risks associated with a persistent foreign
      body, such as chronic infection, enterocutaneous fistulae, and cutaneous
      exposure. Disadvantages of bioprosthetic materials include higher implant cost
      relative to synthetic mesh, limited size of individual sheets in some cases, and
      risk of seroma formation. Bioprosthetic mesh has been used for abdominal wall
      reconstruction for approximately 5 years, so long-term studies are not available.
      Current laboratory and clinical evidence suggests that these materials provide a
      strong, durable musculofascial repair when used for abdominal wall repair.
      Further studies and ongoing clinical experience will be important in determining
      the indications for which bioprosthetic mesh will have the greatest impact.
      Currently available commercial products have distinct differences that result in
      varied clinical biologic and physiologic activity. New products and modifications
      to existing products may further enhance the benefits of bioprosthetic mesh,
      particularly in challenging cases. The use of bioprosthetic mesh has attracted
      interest in a relatively short period of time, with rapidly increasing
      indications and volume of cases successfully performed. Bioprosthetic mesh likely
      will play a progressively greater role in trunk reconstruction in the future.

PMID- 16638464
TI  - Vacuum-assisted closure for the treatment of abdominal wounds.
AB  - Abdominal wall defects pose a significant surgical challenge. The defect may
      result from trauma, infections, previous major surgery, or some combination of
      these etiologies. This article describes the Vacuum-Assisted Closure device (VAC,
      KCI, San Antonio, Texas) and how it can help in treating these defects.

PMID- 16638465
TI  - Updated algorithm for abdominal wall reconstruction.
AB  - Like any clinical regime, the algorithm for abdominal wall reconstruction
      requires routine updating as new options and techniques become available.
      Increased experience and understanding of new applications have allowed for
      improvements to the approach to complex abdominal wall defects. These
      improvements have increased efficiency and decreased risk, particularly in the
      area of staged reconstruction. Surgeons have continued to rely heavily on
      autologous reconstruction and local tissue advancement for long-term dynamic
      support. The current approach to abdominal wall reconstruction is based on
      understanding the literature, clinical experience, and the type of patients seen
      in practice. This article provides surgeons with the basic guidelines to follow
      when faced with complex abdominal wall defects and the tools necessary to solve
      these difficult problems in a responsible and reliable way.

PMID- 16638466
TI  - Inception and evolution of the components separation technique: personal
      recollections.
AB  - This article provides an overview of the components separation technique. It
      describes how the technique was first developed and innovations and improvements
      that have followed through the years.

PMID- 16638467
TI  - Separation of anatomic components method of abdominal wall reconstruction-
      clinical outcome analysis and an update of surgical modifications using the
      technique.
AB  - This article describes some of the benefits and complications of the components
      separation technique. It additionally highlights some of the modifications that
      have been made to the technique over the years.

PMID- 16638468
TI  - Anterior abdominal wall reconstruction.
AB  - Reconstruction of the anterior abdominal wall is based on six basic principles.
      First, the anatomy of the abdominal wall and adjacent donor sites must be
      understood clearly. This includes a complete knowledge of the neurovascular
      anatomy and the arc of rotation of each subunit. The defect then has to be
      exposed completely before the definitive closure is attempted. Once the defect is
      established, abdominal domain is restored with some sort of support. The next
      phase of the repair involves reassigning local tissue to close the defect.
      Distant tissue then is imported from donor sites such as the thigh, if needed.
      Finally, the skin envelope is readjusted and closed. These principles help
      optimize function and restore form, hence achieving the best possible result.

PMID- 16638469
TI  - Abdominal wall reconstruction with free flaps.
AB  - This article addresses the clinical applications of free tissue transfer for
      abdominal wall reconstruction. Details of indications, techniques, and clinical
      examples for the coverage of complex abdominal wall defects are presented.

PMID- 16638470
TI  - Management of abdominal wall defects resulting from complications of surgical
      procedures.
AB  - This article presents the author's personal philosophy for treatment of various
      abdominal wall defects resulting from surgical complications and unfavorable
      results of previous abdominal interventions. The purpose is not to discuss and
      analyze care and management of all soft tissue complications encountered after
      abdominal surgery, but to present the ones for which the plastic surgeon most
      likely will be asked to manage.

PMID- 16638471
TI  - The use of muscle flaps for the management of recalcitrant gastrointestinal
      fistulas.
AB  - Enterocutaneous fistulas can result from various conditions. Although some heal
      spontaneously, others persist or recur. This article describes how using muscle
      flaps may aid in managing recalcitrant gastrointestinal fistulas. Specific cases
      are cited.

PMID- 16638472
TI  - Commentary: guidelines and otolaryngology.

PMID- 16638473
TI  - Clinical practice guideline: acute otitis externa.
AB  - OBJECTIVE: This guideline provides evidence-based recommendations to manage
      diffuse acute otitis externa (AOE), defined as generalized inflammation of the
      external ear canal, which may also involve the pinna or tympanic membrane. The
      primary purpose is to promote appropriate use of oral and topical antimicrobials
      and to highlight the need for adequate pain relief. STUDY DESIGN: In creating
      this guideline, the American Academy of Otolaryngology-Head and Neck Surgery
      Foundation (AAO-HNSF) selected a development group representing the fields of
      otolaryngology-head and neck surgery, pediatrics, family medicine, infectious
      disease, internal medicine, emergency medicine, and medical informatics. The
      guideline was created with the use of an explicit, a priori, evidence-based
      protocol. RESULTS: The group made a strong recommendation that management of AOE
      should include an assessment of pain, and the clinician should recommend
      analgesic treatment based on the severity of pain. The group made recommendations
      that clinicians should: 1) distinguish diffuse AOE from other causes of otalgia,
      otorrhea, and inflammation of the ear canal; 2) assess the patient with diffuse
      AOE for factors that modify management (nonintact tympanic membrane, tympanostomy
      tube, diabetes, immunocompromised state, prior radiotherapy); and 3) use topical
      preparations for initial therapy of diffuse, uncomplicated AOE; systemic
      antimicrobial therapy should not be used unless there is extension outside of the
      ear canal or the presence of specific host factors that would indicate a need for
      systemic therapy. The group made additional recommendations that: 4) the choice
      of topical antimicrobial therapy of diffuse AOE should be based on efficacy, low
      incidence of adverse events, likelihood of adherence to therapy, and cost; 5)
      clinicians should inform patients how to administer topical drops, and when the
      ear canal is obstructed, delivery of topical preparations should be enhanced by
      aural toilet, placing a wick, or both; 6) when the patient has a tympanostomy
      tube or known perforation of the tympanic membrane, the clinician should
      prescribe a nonototoxic topical preparation; and 7) if the patient fails to
      respond to the initial therapeutic option within 48 to 72 hours, the clinician
      should reassess the patient to confirm the diagnosis of diffuse AOE and to
      exclude other causes of illness. And finally, the panel compiled a list of
      research needs based on limitations of the evidence reviewed. CONCLUSION: This
      clinical practice guideline is not intended as a sole source of guidance in
      evaluating patients with AOE. Rather, it is designed to assist clinicians by
      providing an evidence-based framework for decision-making strategies. It is not
      intended to replace clinical judgment or establish a protocol for all individuals
      with this condition and may not provide the only appropriate approach to the
      diagnosis and management of this problem. SIGNIFICANCE: This is the first,
      explicit, evidence-based clinical practice guideline on acute otitis externa, and
      the first clinical practice guideline produced independently by the AAO-HNSF.

PMID- 16638474
TI  - Systematic review of topical antimicrobial therapy for acute otitis externa.
AB  - OBJECTIVE: To determine the efficacy of topical antimicrobials for acute otitis
      externa. STUDY DESIGN: Systematic review and random effects meta-analysis of
      randomized, controlled trials with parallel groups permitting one or more of the
      following comparisons: antimicrobial vs placebo, antiseptic vs antimicrobial,
      quinolone antibiotic vs nonquinolone antibiotic, steroid-antimicrobial vs
      antimicrobial, or antimicrobial-steroid vs steroid. RESULTS: Twenty trials met
      inclusion criteria and 18 had data suitable for pooling. Topical antimicrobials
      increased absolute clinical cure rates over placebo by 46% (95% confidence
      interval [CI], 29% to 63%) and bacteriologic cure rates by 61% (95% CI, 46% to
      76%). No significant differences were noted in clinical cure rates for other
      comparisons, except that steroid alone increased cure rates by 20% compared with
      steroid plus antibiotic (95% CI, 3% to 38%). Quinolone drops increased
      bacteriologic cure rates by 8% compared with nonquinolone antibiotics (95% CI, 1%
      to 16%), but had statistically equivalent rates of clinical cure and adverse
      events. CONCLUSION: Topical antimicrobial is highly effective for acute otitis
      externa with clinical cure rates of 65% to 80% within 10 days of therapy. Minor
      differences were noted in comparative efficacy, but broad confidence limits
      containing small effect sizes make these of questionable clinical significance.
      SIGNIFICANCE: Summary estimates from the 13 meta-analyses can be used to
      facilitate evidence-based management recommendations and clinical practice
      guideline development.

PMID- 16638475
TI  - Improving care of older adults: you can make a difference.

PMID- 16638476
TI  - Management of diabetes mellitus in older persons.

PMID- 16638477
TI  - HIPAA checkups for compliance.

PMID- 16638478
TI  - Effects of hand massage on comfort of nursing home residents.
AB  - Patient comfort is a goal of therapeutic nursing practice and a primary nursing
      function. Residents in nursing homes have many comfort needs including physical,
      psychospiritual, sociocultural, and environmental. These comfort needs are
      addressed by various caregivers including nurses, nursing assistants, and family
      members. Hand massage is a simple comfort intervention that can be incorporated
      readily into routine nursing care activities and conveys caring through touch,
      individual attention, and presence. As an intervention, hand massage promotes
      comfort and facilitates communication between care recipients and caregivers. The
      purpose of this study was to test the effectiveness of hand massage as an
      intervention that affects nursing home residents' comfort and satisfaction.
      Results are presented for 35 participants who received hand massage and 25
      participants in a comparison group. Findings showed no significant differences in
      comfort levels or satisfaction with care over time. Significant group
      differences, however, were found for comfort and satisfaction when measured at
      specific time periods. The discussion highlights these mixed findings and
      presents implications for further development of hand massage as part of nursing
      home residents' care.

PMID- 16638480
TI  - Oral health protocol for the dependent institutionalized elderly.
AB  - Establishing an oral hygiene protocol for the frail and functionally dependent
      elderly should be of special concern to health care providers. The previous
      assessment of a care center, including patients or residents and staff, allows an
      effective strategy to be designed. Oral health protocols are mainly based on the
      daily removal of bacterial plaque from teeth or prostheses (or both), cleaning of
      oral mucosa, and continual oral hydration. These practices are facilitated by the
      use of electric toothbrushes and products such as chlorhexidine, fluoride
      toothpastes, and rinses or gels for dry mouth. This type of protocol should
      include regular collaboration with dental professionals and provide a program of
      continuous training for nursing staff on oral health issues.

PMID- 16638481
TI  - Integration of gerontology content in nongeriatric undergraduate nursing courses.
AB  - During the last several years, a school of nursing in the southeastern United
      States has made concerted efforts to integrate geriatric content into every
      undergraduate course except obstetrics. Even the pediatric nursing course has
      infused content about grandparents, both as care providers for children and as
      extended family members. Faculty expertise and passion for teaching geriatric
      best practices stimulated innovative and creative student experiences without
      overwhelming curricular revision. This article describes how gerontology content
      was incorporated into each curricular area and provides examples of classroom and
      clinical teaching strategies that were successful at this school.

PMID- 16638482
TI  - The OASIS program: redesigning hospital care for older adults.
AB  - A major factor in poor outcomes for hospitalized older adults is the health care
      delivery system. If acute care is not designed to address their altered response
      to illness and treatments, functional needs, and psychosocial issues, they are at
      significant risk for hospital-acquired complications and loss of functionality.
      Each health system should develop its own acute geriatric care program based on
      its resources and a plan for geriatric competency for all its health care
      workers. The OASIS pilot was created by taking elements from programs around the
      country that have succeeded in reengineering care for older adults. This pilot
      addressed the acute care of older patients scattered across 2 medical units in a
      500+ bed community hospital. Outcomes demonstrated that coordinated, geriatric
      specific care had a positive, measurable impact on the quality of care, costs,
      and provided geriatric support to physicians and hospital staff.

PMID- 16638483
TI  - Herbal, prescribed, and over-the-counter drug use in older women: prevalence of
      drug interactions.
AB  - Older adults are at particular risk for drug and herbal interactions because they
      have multiple health problems that require treatment and are generally more
      susceptible to adverse drug effects. This study used a database containing self
      reported herbal, prescription, and over-the-counter (OTC) drugs concurrently
      taken by a sample of 58 women who were aged 65 years or older. Drug-drug
      interactions (DDIs) were identified using a Web-based pharmaceutical program. At
      least 1 moderate or high-risk DDI was identified in 74% of participants, with 136
      total DDIs identified. Fifty-two percent (71) of total DDIs were between
      prescribed and OTC or herbals, with 63% (45) of these involving nonsteroidal
      antiinflammatory drugs (NSAIDs). It is imperative that health care providers
      identify all prescribed, OTC, and herbal drugs taken by their patients and assess
      all interactions in order to avoid the possibility of adverse drug effects.

PMID- 16638486
TI  - Neuromuscular hip biomechanics and pathology in the athlete.
AB  - Although hip arthroscopic techniques have been developed and evolved over the
      last 5 to 10 years to help active athletes, the mechanisms of athletic hip
      injuries across various sports are not well understood. The purpose of this
      article is to review the literature related to the osseous and ligamentous
      support as well as the neuromuscular control strategies associated with hip joint
      mechanics. The neuromuscular contributions to hip stability and mobility with
      respect to gait will be provided because this data represents the largest body of
      knowledge regarding hip function. Further, this article will present and describe
      probable mechanisms of injury in sporting activities most often associated with
      hip injury in the young athlete.

PMID- 16638487
TI  - Clinical examination of the athletic hip.
AB  - This article provides a succinct and complete method for the clinical evaluation
      of the hip. Included are descriptions of examination tests as well as their
      relationships to possible pathology of the hip. The examination is divided into
      five stages: seated, standing, supine, lateral, and prone; with a total of 11
      assessment points. The method for evaluation outlined will assist physicians in
      determining the location and etiology of presenting hip pathologies. As with any
      examination, practice and repetition are essential to gain an appreciation of
      what constitutes a normal as well as an abnormal examination.

PMID- 16638488
TI  - Radiographic and MR imaging of the athletic hip.
AB  - Imaging of the athletic hip has changed significantly over the past 10 years to
      address clinical concerns of intra-articular pathology and femoroacetabular
      impingement. Currently, high-resolution direct MR arthrography of the hip
      provides the best means for evaluating intra-articular pathology. However,
      radiography remains important for the diagnosis of subtle bony irregularities
      associated with femoroacetabular impingement. Therefore, a comprehensive imaging
      strategy requires conventional radiographs and MRI to evaluate intra- and extra
      articular sources of pain. Because of newer surgical techniques, MR
      interpretations should provide description of labral tears and assessment of
      cartilage defects, as well as, capsule/iliofemoral ligament injury,
      femoroacetabular impingement, and tears of the ligamentum teres to aid
      preoperative planning and help provide prognostic information.

PMID- 16638489
TI  - Pediatric athlete hip disorders.
AB  - Injuries of the hip and pelvis in pediatric athletes are receiving increased
      attention. The majority of injuries are soft tissue injuries or apophyseal
      injuries that heal with nonoperative supportive treatment. Unique injury patterns
      can be seen in patients who have underlying pediatric hip disorders such as
      slipped capital femoral epiphysis, and Legg-Perthes disease. With the advent of
      hip arthroscopy and the development of more advanced imaging of the hip through
      MR arthrography, internal derangements of the hip such as labral tears, loose
      bodies, and chondral injuries are being diagnosed and treated with increased
      frequency. This article reviews the more common injuries of the hip and pelvis in
      pediatric athletes.

PMID- 16638490
TI  - The role of hip arthroscopy in the athletic hip.
AB  - Hip joint problems in the athlete can be disabling, yet remain elusive to
      investigation. The arthroscope has proved essential in both the detection and
      treatment of many of these disorders. Less invasive methods with quicker return
      to safe competition has been a sine qua non of sports medicine. The incentive to
      return motivated athletes to a sport has proven fertile ground for advancement of
      arthroscopic techniques. This has been especially exemplified in the rapidly
      evolving field of hip arthroscopy, and has allowed these methodologies to find
      application in the management of patients of all levels of activity. As has been
      stated, the athletic field of competition represents one of the most fertile
      clinical laboratories in the world.

PMID- 16638491
TI  - Labral tears, extra-articular injuries, and hip arthroscopy in the athlete.
AB  - Labral tears in athletes can lead to disabling hip pain and affect their athletic
      performance. Other intra-articular lesions, including chondral injuries, capsular
      abnormalities, and ligamentum teres tears, commonly coexist with acetabular
      labral tears. Isolated athletic injury or repetitive traumatic activity can lead
      to labral tears; however, underlying structural (femoroacetabular impingement)
      and developmental abnormalities predisposing athletes to labral pathology must be
      addressed. Recent studies have demonstrated lesions associated with acetabular
      labral tears, and that labral tears rarely occur as isolated injuries. Return to
      sport is favorable in athletes who have labral tears if they are properly treated
      with arthroscopic intervention.

PMID- 16638492
TI  - A new method for acetabular rim trimming and labral repair.
AB  - In the past, arthroscopic technique for the treatment of a torn acetabular labrum
      was limited to simple debridement of the torn tissue. However, due to recent
      advancements in the understanding of the function of the labrum, it has been
      suggested that labral repair can be beneficial. The purpose of this article is to
      report a new technique for arthroscopic rim trimming of pincer-type
      femoroacetabular impingement and labral repair through the lateral arthroscopic
      portal.

PMID- 16638493
TI  - Arthroscopy for the treatment of femoroacetabular impingement in the athlete.
AB  - Femoroacetabular impingement (FAI) has been recently recognized as a cause of hip
      pain, labral and chondral pathology, early osteoarthritis, and decreased athletic
      performance. Historically, treatment for FAI consisted of an open approach with
      surgical dislocation. It has been suggested that the operative trauma sustained
      during the open procedure may make it difficult for high-level athletes to return
      to play. As a result, an arthroscopic approach to treat FAI has been developed.
      The purpose of this article is to describe the arthroscopic technique for the
      treatment of cam and pincer-type hip impingement.

PMID- 16638494
TI  - Diagnosis and management of traumatic and atraumatic hip instability in the
      athletic patient.
AB  - Although relatively uncommon compared with the shoulder, hip instability can be a
      source of significant disability and is a commonly unrecognized injury. Hip
      instability can be traumatic or atraumatic in origin. Our understanding and
      treatment plan for hip instability due to traumatic events is well established.
      However, our understanding and treatment modalities for hip instability due to
      atraumatic events or repetitive motion in high level athletes are not as well
      defined. In this article, we will review the spectrum of traumatic and atraumatic
      hip instability and discuss the relevant anatomy, history, and physical
      examination findings, imaging studies, and treatment options with a focus on hip
      arthroscopy, and review of the literature.

PMID- 16638495
TI  - Microfracture of the hip in athletes.
AB  - Most studies addressing treatment of chondral injuries have involved the knee.
      Various techniques have been used in the knee. Microfracture has shown excellent
      results in the knee. Chondral injuries of the hip are common in athletes with
      labral tears and femoroacetabular impingement. The microfracture technique is now
      being used in the hip joint. Indications include full-thickness cartilage loss or
      unstable flap on a weight-bearing surface. An important contraindication is the
      patients unwillingness to follow the postoperative protocol and rehabilitation
      plan. The microfracture technique in the hip is similar to that in the knee.
      Postoperatively, patients use a continuous passive motion and are flat foot (20
      lbs.) weightbearing for 8 weeks. Early results following microfracture in the hip
      have been encouraging.

PMID- 16638496
TI  - Rehabilitation following hip arthroscopy.
AB  - The management of hip injuries has evolved significantly in recent years with the
      advancement of arthroscopic techniques. These recent surgical advances require
      establishment of rehabilitation protocols that follow several basic principles
      including (1) consideration of soft-tissue healing constraints, (2) control of
      swelling and pain to limit muscular inhibition and atrophy, (3) early range of
      motion, (4) limitations of weight bearing, (5) early initiation of muscle
      activity and neuromuscular control, (6) progressive lower extremity strengthening
      and proprioceptive retraining, (7) cardiovascular training, and (8) sport
      specific training. The following protocols should not be considered a cookbook
      approach to rehabilitation, rather guidelines that are used to achieve consistent
      outcomes. These guidelines will continue to evolve as we learn more about the hip
      joint and surrounding musculature.

PMID- 16638497
TI  - Sports after total hip replacement.
AB  - The purpose of total hip replacement is to relieve pain, not to make better
      athletes. Still, the modern patient is likely to return to recreation and sports.
      There is no current consensus on the safety of resuming athletics, though a
      surgeon's judgment and a patient's common sense will serve as appropriate
      guidelines. The main concerns are instability, wear, loosening, and fracture.
      Each sport should be evaluated on its potential risk to a joint replacement,
      whether from the force of repetitive injury or the possibility of catastrophic
      failure. Likewise, a surgeon can use techniques, biomaterials, and implants that
      will maximize an athlete's chance of success over time.

PMID- 16638498
TI  - Epilepsy syndromes in infancy.
AB  - An increasing number of infantile epilepsy syndromes have been recognized.
      However, a significant number of infants (children aged 1-24 months) do not fit
      in any of the currently used subcategories. This article reviews the clinical
      presentation, electroencephalographic findings, evolution, and management of the
      following entities: early infantile epileptic encephalopathy, early myoclonic
      epilepsy, infantile spasms/West syndrome, severe myoclonic epilepsy of infancy,
      myoclonic-astatic epilepsy, generalized epilepsy with febrile seizures plus,
      malignant migrating partial seizures of infancy, hemiconvulsions-hemiplegia
      epilepsy, benign myoclonic epilepsy, and benign familial/nonfamilial infantile
      seizures. Issues related to their classification are addressed.

PMID- 16638499
TI  - Randomized double-blind study with prednisone in Sydenham's chorea.
AB  - In this randomized, double-blind, parallel study of a group of 22 children and
      teenagers, prednisone efficacy in acute Sydenham's chorea was assessed. Use of
      prednisone (2 mg/kg/day during 4 weeks, followed by a gradual discontinuation) in
      the 22 patients and in a placebo group (n = 15) was evaluated by a chorea
      intensity score based on presence, distribution, and interference of choreic
      movement on daily activities. Each patient was evaluated by the same pediatric
      neurologist weekly during the first month, followed by evaluation on weeks 8 and
      12, with further evaluations as necessary if choreic movements persisted.
      Although initial chorea intensity was similar in both groups, a significant
      difference was observed after 1 week of medication (P < 0.001) with a larger
      reduction in the prednisone group, that continued until the end of the study.
      Percentage decrease in chorea intensity scale score also was persistently and
      significantly (P < 0.001) greater in the prednisone group. Chorea complete
      remission time with prednisone (mean 54.3 days) was significantly shorter (P <
      0.001) when compared with the placebo group (mean 119.9 days). Seven patients
      presented recurrences, with no difference between groups (13.6% and 26.7% in the
      prednisone and placebo groups, respectively). Severe adverse events to prednisone
      were not observed.

PMID- 16638500
TI  - Pattern of increased cerebral FDG uptake in Down syndrome patients.
AB  - Resting cerebral glucose metabolism was assessed by 18[F]-fluorodeoxyglucose in
      11 Down syndrome patients. Standardized uptake values were determined on a pixel
      by-pixel basis from the measured tissue-activity data. The results revealed a
      mean overall 18[F]-fluorodeoxyglucose uptake in the Down syndrome patients close
      to that observed in the control group, consisting of children and young adults.
      However, the standard deviation of the standardized uptake values was much higher
      in the Down syndrome group in almost all voxels relating to the gray matter. The
      statistical parametric mapping method was applied to compare the cerebral 18[F]
      fluorodeoxyglucose accumulation patterns of the Down syndrome and control groups.
      Six regions (clusters) were found for which the glucose uptake was higher in the
      Down syndrome patients than in the control group. The anatomic localization of
      these clusters was based on magnetic resonance investigations and a brain-atlas
      technique. The localization of the identified clusters with an increased glucose
      metabolism in the Down syndrome patients suggests that these subjects have an
      enhanced resting neuronal activity in cortical areas involved in reasoning,
      cognition, and speech as compared with normal subjects.

PMID- 16638501
TI  - Utility of multimodal evoked potentials study in neurofibromatosis type 1 of
      childhood.
AB  - A group of 21 children affected by neurofibromatosis type 1 has been investigated
      with the aim of studying multimodal (visual, brainstem auditory, and
      somatosensory) evoked potentials and their correlations with neurologic,
      electroencephalographic, and cranial magnetic resonance imaging. In the present
      series, cranial magnetic resonance imaging and evoked potentials were the most
      frequently abnormal instrumental tests. In approximately two thirds of the cases
      at least one of the evoked potentials (particularly visual and auditory evoked
      potentials) was compromised, always without clinical signs of related sensory
      (visual, auditory, and somatosensory) pathway pathology and sometimes in the
      absence of magnetic resonance imaging signs of central nervous system
      involvement. This study indicates that in patients with neurofibromatosis type 1,
      multimodal evoked potentials are useful and should be part of the diagnostic
      protocol of encephalic lesions together with magnetic resonance imaging. The use
      of both methods could aid in early detection of central nervous system
      dysfunction in both the initial evaluation of disease and its follow-up.

PMID- 16638502
TI  - Myostatin expression in muscular dystrophies and mitochondrial
      encephalomyopathies.
AB  - The demonstration that myostatin may negatively regulate muscle mass in adult
      individuals has raised the possibility of targeting the myostatin pathway in
      order to increase muscle growth in a variety of muscle degenerative and wasting
      conditions. In this regard, blockade of endogenous myostatin results in anatomic,
      biochemical, and physiologic improvement in the dystrophic phenotype in the mdx
      mouse. Moreover, myostatin messenger ribonucleic acid levels are decreased in the
      regenerated muscle of these mice, suggesting that myostatin may also be involved
      in the pathogenesis of the disease. To gain further insight into the possible
      role of myostatin in muscle degenerative diseases, the present work investigates
      the expression of muscle myostatin in children with muscular dystrophies and
      mitochondrial encephalomyopathies. No differences in the pattern of myostatin
      expression were evident in any case, even in those patients with prominent
      muscular atrophy. These findings suggest that muscle loss that can be observed in
      muscle degenerative diseases does not depend on changes in myostatin expression.

PMID- 16638503
TI  - Low- and high-dose botulinum toxin A treatment: a retrospective analysis.
AB  - Upper limb botulinum toxin A doses in children are empirical, determined by the
      size of the muscle, seeking to avoid excessive weakness and deterioration of
      function. This study reports the effects and side effects of botulinum toxin
      treatment on upper limb impairment and function in 18 children with spastic or
      dystonic hyperactivity. A total of 54 treatments were divided into low-dose or
      high-dose groups according to the dose used for the target muscles. The outcome
      measurements included modified Ashworth Scale, passive range of movement, various
      grips, bimanual functions, movement pattern, House classification of upper
      extremity use, and subjective ratings of function and cosmetic appearance. In the
      functional goal group, children benefited in terms of reduction in muscle tone at
      elbow and wrist, and increase in passive wrist extension and House classification
      scores. A significant difference between the groups was observed in the House
      classification, favoring the low-dose group. In the nonfunctional goal group, a
      significant difference was detected in subjective parental cosmetic ratings,
      favoring the high dosage. Side effects were few and occurred mostly in the high
      dose group. In conclusion, the use of higher doses in the spastic upper limb does
      not necessarily yield superior results compared with lower doses but increases
      the incidence of side effects.

PMID- 16638504
TI  - Outcomes of children with infantile spasms after perinatal stroke.
AB  - The object of this study was to describe the outcomes of children with infantile
      spasms resulting from perinatal stroke. We used International Classification of
      Diseases, Ninth Revision (ICD-9) searches of billing records to identify 110
      children with infantile spasms examined at our hospital from 1998 through 2005.
      Five of the 99 with symptomatic spasms (5%) had perinatal stroke. An additional
      five children with spasms caused by perinatal stroke were identified from
      pediatric stroke clinic records. Seven of the 10 children with spasms due to
      perinatal stroke presented with stroke as neonates. Three initially appeared
      healthy but were diagnosed with "presumed perinatal stroke" after radiographic
      imaging for their spasms evaluation. Median age at last follow-up was 6.3 years:
      9 (90%) had epilepsy, 8 (80%) manifested cognitive impairment, and all (100%) had
      cerebral palsy. The three children who had delayed presentation of "presumed
      perinatal stroke" had better epilepsy and cognitive outcomes than the seven with
      neonatal presentation (P = 0.03). Perinatal stroke accounts for 5% of symptomatic
      spasms and results in high rates of chronic disability similar to those observed
      with other types of symptomatic spasms. However, a subgroup of children with
      spasms caused by delayed presentation of "presumed perinatal stroke" appears to
      have better epilepsy and cognitive outcomes.

PMID- 16638505
TI  - Are males with Duchenne muscular dystrophy at risk for reading disabilities?
AB  - Males with Duchenne muscular dystrophy have sub-average cognitive capacities and
      may manifest more specifically language-related deficits. In the current study,
      the information-processing capacity, reading performance, and behavioral
      functioning of 25 Dutch males with Duchenne muscular dystrophy (mean age 10.1
      years) were systematically assessed. This study relied on the use of a new
      battery of tests to explore more precisely reading disabilities in males with
      Duchenne muscular dystrophy. Five of the males had serious reading problems and
      another five had moderate reading problems, which indicates that reading problems
      are significantly more common in males with Duchenne muscular dystrophy than in
      males from a normal population. These reading problems were independent of the
      level of information processing and behavioral functioning. Implications of these
      findings and possible directions for future research are discussed, especially
      with regard to the early detection and treatment of reading problems in males
      with Duchenne muscular dystrophy.

PMID- 16638506
TI  - Infantile spinocerebellar ataxia type 6: relationship to episodic ataxia type 6.
AB  - Spinocerebellar ataxia type 6 is one of the hereditary progressive cerebellar
      ataxias first described in 1997. Genetic studies have identified the defect as
      abnormal expansion of CAG trinucleotide repeat in 1 alpha subunit of the calcium
      channel gene located on chromosome 19p13. The symptomatic individuals have 20 or
      23 repeats in contrast to normal individuals who manifest 19 or less CAG repeats.
      Most of the earlier reports indicate the age of onset of symptoms to be after the
      third decade. This report presents a patient with episodic symptoms soon after
      birth, which is unusual, and to our knowledge this is the youngest reported case.
      The clinical features of spinocerebellar ataxia type 6 are variable. The mode of
      inheritance and the common symptoms of this condition are also discussed.

PMID- 16638507
TI  - Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure
      disorder?
AB  - This report describes the case of a 4 1/2-year-old female with developmental
      delay and tonic-clonic seizures, persistently elevated serum alkaline phosphatase
      activity, and low serum pyridoxal 5'-phosphate. Born at term to consanguineous
      parents, she was dysmorphic and delayed at 5 months. At 11 months, seizures and
      microcephaly were evident but skeletal and cerebral imaging, karyotyping, and
      genetic metabolic tests were unremarkable. Serum alkaline phosphatase activity,
      however, was elevated (1.3 +/- 0.6 times greater than the upper limit of normal)
      on seven occasions between 5 months and 4(1/2) years of age. Hyperphosphatasia
      with neurologic deficit (MIM #239300), a rare autosomal recessive disorder, was
      diagnosed. The low serum levels of pyridoxal 5'-phosphate (6 nmol/L; normal >20
      nmol/L) prompted a pyridoxine challenge. A clinically significant but paradoxical
      response was observed. On electroencephalography, diffuse delta slow waves (1-2
      Hz) were observed, suggestive of stage 3 or 4 slow-wave sleep. With daily
      administration of 100 mg pyridoxine and withdrawal of phenobarbital, seizures
      were not evident. We suggest that serum alkaline phosphatase should be measured
      in cases of seizures with paradoxical electroencephalographic response to
      pyridoxine. Conversely, pyridoxine challenge should be considered in cases of
      hyperphosphatasia with seizures and neurologic deficit.

PMID- 16638508
TI  - Serial changes on diffusion-weighted magnetic resonance imaging in encephalitis
      or encephalopathy.
AB  - It is recognized that diffusion-weighted magnetic resonance imaging is a
      sensitive method of detecting cerebral lesions in various neurologic disorders.
      This report presents two patients with acute encephalitis or encephalopathy who
      manifested similar serial changes on diffusion-weighted magnetic resonance
      imaging. Clinically, Patient 1, a 2-year-old male, was diagnosed as having
      hemiconvulsion-hemiplegia-epilepsy syndrome and Patient 2, a 9-month-old male,
      acute encephalitis associated with exanthema subitum. Despite the different
      etiology and the distribution of lesions, diffusion-weighted magnetic resonance
      imaging of these two patients revealed high-intensity lesions in the subcortical
      white matter in the acute phase, and then in the cortex, or basal ganglia, or
      both. In the convalescent phase, high-intensity lesions disappeared and brain
      atrophy developed. These serial changes were not recognized using other
      conventional methods. Although the exact mechanism for these serial changes
      remains unknown, these changes might reflect some pathogenic mechanism in acute
      encephalopathy or encephalitis.

PMID- 16638509
TI  - Opsoclonus-myoclonus associated with celiac disease.
AB  - Celiac disease may be associated with various neurologic manifestations, most
      commonly cerebellar ataxia. This report describes a 2-year-old male who presented
      with opsoclonus-myoclonus syndrome including action myoclonus, palpebral flutter,
      opsoclonus, and ataxia. Given the severity of ataxia, the child was unable to sit
      or walk independently. Brain magnetic resonance imaging was normal on two
      occasions (4-week interval). Oligoclonal bands were found in the cerebrospinal
      fluid. Blood and serum examinations were unremarkable, with no evidence of
      infectious seroconversion. However autoantibody testing indicated the presence of
      antigliadin antibodies of immunoglobulin A subtype, anti-endomysial antibodies,
      and anti-CV2 antibodies that were not, however, detected in the cerebrospinal
      fluid. Duodenal biopsy documented villous atrophy confirming the diagnosis of
      celiac disease. This case confirms that initial presentation of celiac disease
      may be restricted to neurologic features. We suggest that a search for evidence
      for celiac disease should be included in the evaluation of opsoclonus-myoclonus.

PMID- 16638510
TI  - Acute necrotizing encephalopathy associated with hemophagocytic syndrome.
AB  - A 7-year-old female suddenly exhibited high fever and convulsions, and entered a
      semi-coma. She also had thrombocytopenia, elevated aminotransferase, prolonged
      prothrombin time and activated partial thromboplastin time, and hemophagocytes in
      the bone marrow. The brain magnetic resonance imaging revealed multiple low
      intensity areas on the T1-weighted images, and high-intensity areas on the T2
      weighted images bilaterally in the thalamus, the dorsal part of the pons, and the
      cerebellar white matter. The patient was diagnosed as having both acute
      necrotizing encephalopathy and hemophagocytic syndrome. Serum and cerebrospinal
      fluid interleukin-6 and tumor necrosis factor-alpha were elevated to the same
      high levels (serum:cerebrospinal fluid interleukin-6, 103:101 pg/mL; tumor
      necrosis factor-alpha 753:753 pg/mL). The clinical symptoms and the magnetic
      resonance imaging findings improved immediately after the administration of
      dexamethasone. These results suggest that the hypercytokinemia and the
      hyperpermeability of both the blood-brain barrier and the capillary walls of the
      central nervous system might be essential in the pathogenesis of acute
      necrotizing encephalopathy, and that early steroid therapy might be effective in
      these conditions.

PMID- 16638511
TI  - Optic nerve hypoplasia and growth hormone deficiency in a cholestatic infant.
AB  - This report describes a 4-month-old male with cholestasis, hypoglycemia, and
      short stature. Symptoms appeared since neonatal age with jaundice, hypoglycemia,
      neurologic manifestations, and later with short stature. Laboratory investigation
      was indicative for cholestasis. Further research indicated isolated growth
      hormone deficiency with accompanying optic nerve hypoplasia. Unexplained
      hypoglycemia and cholestasis in neonates have to be investigated for growth
      hormone deficiency. Moreover, in cases with unexplained cholestasis, timely
      recognition of hypoglycemia is important for the early diagnosis of the disorder
      before the appearance of growth retardation.

PMID- 16638512
TI  - Antiepileptic drugs: a case report in a pregnancy with a neural tube defect.
AB  - While receiving lamotrigine, a patient pregnant with triplets suffered a double
      fetal neural tube defect. Plasma homocysteine, folate, vitamins B12 and B6
      (pyridoxal phosphate), and red cell folate levels were measured in samples while
      she was receiving folic acid therapy for 1 month during the second trimester of
      pregnancy. Some mutations were sought, involved in homocysteine metabolism and
      linked with the folate metabolism. Her results were compared with those of a
      pregnant woman with normal triplets and with those of 58 pregnant women, with a
      normal pregnancy. Results indicated a decrease in vitamin B12 and B6 values in
      plasma in the patient, and a genotype AG (polymorphism A66G) was observed, but
      was not found in the pregnant woman with normal triplets. Even if lamotrigine
      therapy is not known to be associated with significant changes in red cells or in
      serum folate, periconceptional folic acid supplementation is counseled for women,
      along with periconceptional B12 and B6 vitamin supplementation when their plasma
      values are decreased.

PMID- 16638513
TI  - Impact of treating sleep apnea in a child with autism spectrum disorder.
AB  - Sleep disorders can affect daytime functioning in a variety of neurologic
      conditions, including autism spectrum disorder. This report describes
      improvements in sleep, social communication, attention, repetitive behaviors, and
      hypersensitivity after adenotonsillectomy for obstructive sleep apnea in a 5-year
      old female with an autism spectrum disorder. Improvements were documented via pre
      and postsurgical measures of parent report, polysomnography, validated sleep and
      behavior scales, and the Autism Diagnostic Observation Schedule. Identification
      and treatment of sleep disorders, including obstructive sleep apnea, may improve
      daytime behavior in children with autism spectrum disorders.

PMID- 16638514
TI  - Minor head trauma-induced sporadic hemiplegic migraine coma.
AB  - Familial hemiplegic migraine is a severe, rare subtype of migraine. Gene
      mutations on chromosome 19 have been identified in the calcium channel, voltage
      dependent, P/Q type, alpha-1A subunit gene (chromosome 19p13) for familial
      hemiplegic migraine. Recently a gene mutation (Serine-218-Leucine) for a dramatic
      syndrome associated with familial hemiplegic migraine, commonly named "migraine
      coma", has implicated exon 5 of this gene. The occurrence of trivial head trauma,
      in such familial hemiplegic migraine patients, may also be complicated by severe,
      sometimes even fatal, cerebral edema and coma occurring after a lucid interval.
      Sporadic hemiplegic migraine shares a similar spectrum of clinical presentation
      and genetic heterogeneity. The case report presented in this article implicates
      the involvement of the Serine-218-Leucine mutation in the extremely rare disorder
      of minor head trauma-induced migraine coma. We conclude that the Serine-218
      Leucine mutation in the calcium channel, voltage-dependent, P/Q type, alpha-1A
      subunit gene is involved in sporadic hemiplegic migraine, delayed cerebral edema
      and coma after minor head trauma.

PMID- 16638516
TI  - Immune activation in autism.

PMID- 16638517
TI  - Stimulus-sensitivity in treated status epilepticus.

PMID- 16638520
TI  - Catalyzing quality of care improvements for women.

PMID- 16638521
TI  - Gender differences across racial and ethnic groups in the quality of care for
      acute myocardial infarction and heart failure associated with comorbidities.
AB  - This paper provides important insights on gender differences across racial and
      ethnic groups in a Medicare population in terms of the quality of care received
      for acute myocardial infarction (AMI) and congestive heart failure (CHF) in
      association with diabetes or hypertension/end-stage renal disease (ESRD). Both
      race/ethnicity and gender are associated with differences in the diagnostic
      evaluation and treatment of Medicare recipients with these conditions. In the AMI
      group, non-Hispanic Black and Hispanic patients of both genders were less likely
      to receive aspirin or beta-blockers than non-Hispanic Whites. These differences
      persisted for Hispanic women and men even when they presented with ESRD or
      diabetes. Rates for smoking cessation counseling were among the lowest among non
      Hispanic Blacks and Hispanics with AMI-diabetes and non-Hispanic blacks with AMI
      hypertension/ESRD. Gender comparisons within racial groups for the AMI and AMI
      diabetes groups show that among non-Hispanic Whites, women were less likely to
      receive aspirin and beta-blockers. No gender differences were noted among non
      Hispanic Black and Hispanic Medicare recipients. In the CHF group, Hispanics were
      the racial/ethnic group least likely to have an assessment of left ventricular
      function (LVF), even if they had diabetes and had lower rates of angiotensin
      converting enzyme inhibitor therapy or even if they had combined CHF
      hypertension/ESRD. Gender comparisons in both the CHF and CHF-hypertension/ESRD
      groups show that non-Hispanic White women were less likely to have an LVF
      assessment than non-Hispanic White men. Among all subjects, having comorbidities
      with AMI was not associated with higher markers of quality cardiovascular care.
      Closing the many gaps in cardiovascular care must target the specific needs of
      women and men across racial and ethnic groups.

PMID- 16638522
TI  - Gender differences across racial and ethnic groups in the quality of care for
      diabetes.
AB  - High-quality care for diabetes is based on proper prevention, coordination of
      care among a multidisciplinary team of health care professionals, enhanced
      patient-provider relationships, and patient self-management skills. This paper
      discusses gender differences across racial and ethnic groups in the quality of
      care for type 2 diabetes according to 10 measures defined by the National
      Healthcare Quality Report and the National Healthcare Disparities Report. These
      measures include 5 process measures and one composite measure derived from the
      Medical Expenditure Panel Survey and 4 outcome measures derived from the
      Healthcare Cost and Utilization Project. National rates for 2 process measures-
      measurement of HbA1c (women 89.70% versus men 90.10%) and lipid profile (women
      92.9% versus men 95.3%)--are high, but only 28.9% of women and 33.9% of men with
      diabetes received all 5 recommended process measures (HbA1c, lipid profile, eye
      exam, foot exam, and influenza immunization). Screening rates for retinal and
      foot exams and influenza immunization should be improved for all, but the need is
      particularly urgent for Hispanics and non-Hispanic blacks. Women and men have
      similar rates of hospital admissions for uncontrolled diabetes, but rates for
      lower extremity amputations were higher for men, particularly non-Hispanic blacks
      and Hispanics. Avoidable hospitalizations for diabetes decreased as income
      increased across racial/ethnic groups, but other factors (e.g., quality of
      primary care, age, relationship with providers, patients' self-management skills)
      may influence such rates. Moreover, any improvements in the diabetes outcomes
      measures may lag many years behind any measurable improvements in quality of
      care. Well-designed interventions that reallocate resources for diabetes self
      care should be developed to ensure that gender differences are addressed across
      racial/ethnic groups. Because much of this care involves the management of risk
      factors, self-management education should be tailored to the lifestyles and
      beliefs specific to gender and racial/ethnic groups.

PMID- 16638523
TI  - Women's health care utilization and expenditures.
AB  - This study examines women's use and expenditures for medical care in the US. In
      2000, 91% of women aged 18 years and older used any form of health care services.
      Overall, 82% of adult women reported an ambulatory care visit, and 11% had an
      inpatient hospital stay. Mean expense per person with expenses was 3219 dollars
      for that year. We examined use and expenditures by sociodemographic
      characteristics. The most notable findings indicate that women with private
      insurance and those on Medicaid are more likely to use health services than
      uninsured women. White women, compared to black and Hispanic women, are more
      likely to have an ambulatory care visit, buy prescription drugs, and use
      preventive health care services. In addition, white and Hispanic women pay a
      higher proportion of medical care expenses out-of-pocket than do black women.
      Finally, nearly 30% of older women in fair or poor health spent 10% or more of
      their income on medical care. Preventable disparities in access to and receipt of
      care are unacceptable. To improve the quality of health care for all women, it is
      important for policymakers to understand the factors that influence their
      utilization and expenditures for medical care. Data collection, analysis, and
      reporting by race, ethnicity, and primary language across federally supported
      health programs are essential to help identify, understand the causes of,
      monitor, and eventually eliminate disparities.

PMID- 16638524
TI  - Preventive health examinations: a comparison along the rural-urban continuum.
AB  - In this analysis, Medical Expenditure Panel Survey data from 2000 were used to
      examine differences in reports of preventive health service utilization in 4
      types of counties: large metropolitan counties, small metropolitan counties,
      counties adjacent to metropolitan places, and counties not adjacent to
      metropolitan areas or with fewer than 10,000 residents. Women from counties with
      10,000 or fewer residents and not adjacent to a metropolitan county, classified
      as rural residents, were less likely to report a number of preventive health
      examinations during the previous 2 years. Rural women were less likely to obtain
      blood cholesterol tests, dental exams, and mammograms during the previous 2 years
      when compared to women from large metropolitan counties. Rural women were more
      likely to obtain blood pressure checks during the previous year when compared to
      the metropolitan women. Findings for exams that occurred during the preceding 1-
      and 2-year periods are reported for blood pressure checks, blood cholesterol
      checks, physical exams, colon cancer screening, dental exams, breast exams,
      mammograms, and Pap smears.

PMID- 16638525
TI  - Quality of health care for older women: what do we know?
AB  - As the proportion of the population age 65 and over continues to grow--to a
      projected 20.5% or 77.2 million by the year 2040--tracking the quality, access,
      and receipt of care for older women becomes more important, since the majority of
      older citizens are women. This article establishes a rough baseline for the
      quality of care, primarily preventive care, received by older women compared to
      older men, using selected measures and data of the 2004 National Healthcare
      Quality Report and National Healthcare Disparities Report. It highlights
      significant differences between women and men, as well as differences for racial,
      ethnic, and educational subgroups. Generally, older non-Hispanic white women
      frequently score higher than their Hispanic and non-Hispanic black counterparts,
      and more educated women often score significantly higher than their less-educated
      peers on several measures of quality of care. Compared to their male
      counterparts, older women are significantly less likely to have any colorectal
      screening test, to keep high blood pressure under control, and to receive aspirin
      or beta-blockers upon hospital admission or discharge for acute myocardial
      infarction. Results are mixed for the process measures related to diabetes, but
      improvements are clearly needed toward increased rates of eye and foot
      examinations. Rates of influenza and pneumococcal vaccinations are low but can be
      improved through Medicare-covered services. We also found that older women are
      screened less often for breast cancer than those ages 40 to 64. There is still a
      pervasive lack of knowledge in the research and clinical communities about the
      unique health care needs of and appropriate processes of care for older adults.
      More research needs to focus on the quality of care for this growing population
      in order to allow the development of geriatric-based quality measures and models
      of care that will set the standards of healthcare for older adults in general,
      and older women in particular.

PMID- 16638526
TI  - On the trail of prometheus.

PMID- 16638527
TI  - Sometimes intermediates. Do the job!
AB  - The SARS coronavirus main proteinase is a prime target for antiviral therapy. In
      this issue of Chemistry & Biology, Wu et al. describe potent inhibition of the
      enzyme by benzotriazole esters, which were originally obtained as intermediates
      in the synthesis of lopinavir derivatives .

PMID- 16638528
TI  - Pharmacogenetics: yeast lead the way.
AB  - In this issue of Chemistry & Biology, Perlstein et al. use genetically diverse
      strains of yeast to study the genetic basis of differences in cellular responses
      to small molecules. Their results suggest that drug responses are regulated by a
      limited number of loci, and that this system can identify clusters of
      functionally similar molecules.

PMID- 16638529
TI  - Chemical genetic identification of the IGF-linked pathway that is mediated by
      STAT6 and MFP2.
AB  - Insulin-like growth factor 2 (IGF2) is a potent mitogen whose deregulation plays
      a role in developing liver, breast, and prostate cancers. Here, we take a small
      molecule approach to investigate molecular pathways that modulate IGF2 signaling,
      by using chromeceptin, a synthetic molecule that selectively impairs the
      viability and growth of IGF2-overexpressing hepatocellular carcinoma cells.
      Affinity purification revealed that chromeceptin binds to multifunctional protein
      2 (MFP-2), a seemingly multifunctional enzyme implicated in peroxisomal beta
      oxidation. The small molecule-protein interaction stimulates the expression of
      IGF binding protein 1 (IGFBP-1) and suppressor of cytokine signaling-3 (SOCS-3),
      two cellular attenuators of the IGF signals, through activation of signal
      transducers and activators of transcription 6 (STAT6). The results underline the
      importance of STATs in IGF/insulin regulation, and they implicate a new pathway
      for STAT6 activation that is amenable to small-molecule intervention.

PMID- 16638530
TI  - Multivalent fertilinbeta oligopeptides: the dependence of fertilization
      inhibition on length and density.
AB  - The sperm protein fertilinbeta, a member of the ADAM family of proteins, is
      implicated in sperm-egg binding in all mammals studied to date. Multivalent
      inhibitors containing the three amino acid binding sequence of fertilinbeta, ECD,
      have been shown previously to be more effective inhibitors of fertilization than
      their monovalent counterparts. Here, we probed sperm-egg interactions with
      ruthenium-catalyzed ring-opening metathesis polymers that contained from 3 to 70
      ECD pharmacophores in densities ranging from 10% to 100%. Evaluation of the
      polymer potencies, and synthesis of a triblock copolymer from two building
      blocks, revealed that two multivalent contacts are sufficient for maximal
      inhibition, and that the distance between ECD pharmacophores required is 7-9
      monomers spanning 4-5 nm. We conclude that inhibition requires recruitment of two
      receptors on the egg surface into an inhibitory complex.

PMID- 16638531
TI  - Stable benzotriazole esters as mechanism-based inactivators of the severe acute
      respiratory syndrome 3CL protease.
AB  - Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus
      that infected more than 8000 individuals and resulted in more than 800 fatalities
      in 2003. Currently, there is no effective treatment for this epidemic. SARS
      3CL(pro) has been shown to be essential for replication and is thus a target for
      drug discovery. Here, a class of stable benzotriazole esters was reported as
      mechanism-based inactivators of 3CL(pro), and the most potent inactivator
      exhibited a k(inact) of 0.0011 s(-1) and a K(i) of 7.5 nM. Mechanistic
      investigation with kinetic and mass spectrometry analyses indicates that the
      active site Cys145 is acylated, and that no irreversible inactivation was
      observed with the use of the C145A mutant. In addition, a noncovalent,
      competitive inhibition became apparent by using benzotriazole ester surrogates in
      which the bridged ester-oxygen group is replaced with carbon.

PMID- 16638532
TI  - Genetic engineering in Streptomyces roseosporus to produce hybrid lipopeptide
      antibiotics.
AB  - Daptomycin is a lipopeptide antibiotic produced by a nonribosomal peptide
      synthetase (NRPS) in Streptomyces roseosporus. The holoenzyme is composed of
      three subunits, encoded by the dptA, dptBC, and dptD genes, each responsible for
      incorporating particular amino acids into the peptide. We introduced expression
      plasmids carrying dptD or NRPS genes encoding subunits from two related
      lipopeptide biosynthetic pathways into a daptomycin nonproducing strain of S.
      roseosporus harboring a deletion of dptD. All constructs successfully
      complemented the deletion in trans, generating three peptide cores related to
      daptomycin. When these were coupled with incomplete methylation of 1 amino acid
      and natural variation in the lipid side chain, 18 lipopeptides were generated.
      Substantial amounts of nine of these compounds were readily obtained by
      fermentation, and all displayed antibacterial activity against gram-positive
      pathogens.

PMID- 16638533
TI  - Directed mutagenesis alters the stereochemistry of catalysis by isolated
      ketoreductase domains from the erythromycin polyketide synthase.
AB  - The ketoreductase (KR) domains eryKR(1) and eryKR(2) from the erythromycin
      producing polyketide synthase (PKS) reduce 3-ketoacyl-thioester intermediates
      with opposite stereospecificity. Modeling of eryKR(1) and eryKR(2) showed that
      conserved amino acids previously correlated with production of alternative
      alcohol configurations lie in the active site. eryKR(1) domains mutated at these
      positions showed an altered stereochemical outcome in reduction of (2R, S)-2
      methyl-3-oxopentanoic acid N-acetylcysteamine thioester. The wild-type eryKR(1)
      domain exclusively gave the (2S, 3R)-3-hydroxy-2-methylpentanoic acid N
      acetylcysteamine thioester, while the double mutant (F141W, P144G) gave only the
      (2S, 3S) isomer, a switch of the alcohol stereochemistry. Mutation of the
      eryKR(2) domain, in contrast, greatly increased the proportion of the wild-type
      (2R, 3S)-alcohol product. These data confirm the role of key residues in
      stereocontrol and suggest an additional way to make rational alterations in
      polyketide antibiotic structure.

PMID- 16638534
TI  - High-throughput mutagenesis to evaluate models of stereochemical control in
      ketoreductase domains from the erythromycin polyketide synthase.
AB  - Ketoreductase (KR) activities help determine the stereochemistry of the products
      of modular polyketide synthases (PKSs). For example, domains eryKR(1) and
      eryKR(2), contained, respectively, in the first and second extension modules of
      the erythromycin-producing PKS, reduce 3-ketoacyl-thioester intermediates with
      opposite stereospecificity. Amino acid motifs that correlate with stereochemical
      outcome have been identified in KRs. We have used saturation mutagenesis of these
      motifs in eryKR(1) and eryKR(2), and a microplate-based screen of such mutants
      for activity against (9R, S)-trans-1-decalone, to identify candidate enzymes
      potentially altered in stereocontrol. Active mutants were reassayed with (2R, S)
      2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, and the alcohol
      products were analyzed by chiral HPLC. Variant enzymes were found with either
      altered substrate selectivity for the (2R) or (2S) substrate or altered
      stereospecificity of reduction, or both, further highlighting the importance of
      these motifs in stereochemical control.

PMID- 16638535
TI  - Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2
      alkynoic acids.
AB  - 2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against
      Mycobacterium smegmatis and Mycobacterium bovis BCG. At subinhibitory
      concentrations, M. smegmatis rapidly transformed [1-(14)C]-2-hexadecynoic acid
      into endogenous fatty acids and elongated them into mycolic acids. Toxic
      concentrations of 2-hexadecynoic acid resulted in accumulation of 3
      ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic
      acid, an inhibitor of fatty acid degradation. The combination of these two
      metabolites is necessary to achieve the inhibition of M. smegmatis. We conclude
      that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty
      acid biosynthesis, and fatty acid degradation, pathways of significant importance
      for mycobacteria.

PMID- 16638536
TI  - Profiling a Taxol pathway 10beta-acetyltransferase: assessment of the specificity
      and the production of baccatin III by in vivo acetylation in E. coli.
AB  - The 10beta-acetyltransferase on the biosynthetic pathway of the antineoplastic
      drug Taxol catalyzes the regiospecific transfer of the acetyl group of acetyl
      coenzyme A (CoA) to 10-deacetylbaccatin III. We demonstrate that in addition to
      acetyl group transfer, the overexpressed enzyme also catalyzes the exchange of
      propionyl and n-butyryl from the corresponding CoA thioester to the hydroxyl
      group at C10 of the cosubstrate. Also, in vivo studies revealed that E. coli,
      producing endogenous acetyl-CoA and overexpressing the recombinant
      acetyltransferase, can convert exogenously supplied 10-deacetylbaccatin III to
      baccatin III. Potentially, this heterologous in vivo production method in
      bacteria could be optimized to couple various unnatural acyl-CoA analogs to
      myriad amino and/or hydroxyl acceptors by acyltransferase catalysis; conceivably,
      this process could facilitate the preparation of second-generation Taxols.

PMID- 16638537
TI  - Revealing complex traits with small molecules and naturally recombinant yeast
      strains.
AB  - Here we demonstrate that natural variants of the yeast Saccharomyces cerevisiae
      are a model system for the systematic study of complex traits, specifically the
      response to small molecules. As a complement to artificial knockout collections
      of S. cerevisiae widely used to study individual gene function, we used 314- and
      1932-member libraries of mutant strains generated by meiotic recombination to
      study the cumulative, quantitative effects of natural mutations on phenotypes
      induced by 23 small-molecule perturbagens (SMPs). This approach reveals synthetic
      lethality between SMPs, and genetic mapping studies confirm the involvement of
      multiple quantitative trait loci in the response to two SMPs that affect
      respiratory processes. The systematic combination of natural variants of yeast
      and small molecules that modulate evolutionarily conserved cellular processes can
      enable a better understanding of the general features of complex traits.

PMID- 16638538
TI  - Conversion of a ribozyme to a deoxyribozyme through in vitro evolution.
AB  - An RNA ligase ribozyme was converted to a corresponding deoxyribozyme through in
      vitro evolution. The ribozyme was prepared as a DNA molecule of the same
      sequence, and had no detectable activity. A population of randomized variants of
      this DNA was constructed and evolved to perform RNA ligation at a rate similar to
      that of the starting ribozyme. When the deoxyribozyme was prepared as an RNA
      molecule of the same sequence, it had no detectable activity. Thus, the
      evolutionary transition from an RNA to a DNA enzyme represents a switch, rather
      than a broadening, of the chemical basis for catalytic function. This transfer of
      both information and function is relevant to the transition between two different
      genetic systems based on nucleic acid-like molecules, as postulated to have
      occurred during the early history of life on Earth.

PMID- 16638541
TI  - Physiopathology of right ventricular failure.
AB  - The physiopathology of right ventricular failure after repair of tetralogy of
      Fallot is complex. While primarily reflecting chronic volume overload resulting
      from pulmonary regurgitation, its determinants reflect a varied contribution of
      different boundary conditions. The competence of the outflow tract, right
      ventricular afterload, and the integrity of right ventricular diastolic
      performance are all crucial elements to the long-term responses of the right
      ventricle. When adverse, chronic right ventricular volume overload may lead to
      exercise intolerance, congestive cardiac failure, and both atrial and ventricular
      arrhythmia. Indeed, there appears to be a close relationship between the
      mechanical properties of the right ventricle and its electrical stability. In
      this chapter the determinants of pulmonary incompetence and its secondary effects
      on right ventricular function and performance, and mechano-electric interactions
      will be discussed.

PMID- 16638542
TI  - Indications and timing of pulmonary valve replacement after tetralogy of Fallot
      repair.
AB  - Surgical management of tetralogy of Fallot results in anatomic and functional
      abnormalities in the majority of patients. Although right ventricular volume load
      due to severe pulmonary regurgitation can be tolerated for years, there is now
      evidence that the compensatory mechanisms of the right ventricular myocardium
      ultimately fail and that if the volume load is not eliminated or reduced the
      dysfunction might be irreversible. In light of that data and with better
      understanding of risk factors for adverse outcomes late after tetralogy of Fallot
      repair, many centers are now recommending early pulmonary valve replacement
      before symptoms of heart failure develop. This article reviews the
      pathophysiology of chronic right ventricular volume load after tetralogy of
      Fallot repair and the risks and benefits of pulmonary valve replacement. Finally,
      recommendations for timing and indications for pulmonary valve replacement are
      given.

PMID- 16638543
TI  - Percutaneous pulmonary valve implantation.
AB  - Percutaneous implantation of valves is a fast evolving field in interventional
      cardiology. Acquired pulmonary valve disease is uncommon; however, right
      ventricular outflow tract dysfunction is one of the common indications of
      reoperations during late follow-up of repaired congenital heart disease. The
      impact of pulmonary valvular dysfunction on right ventricular function during
      late follow-up of patients with adult congenital heart disease has led to earlier
      intervention. The importance of a technique with lower morbidity and mortality,
      good patient acceptance, and efficacy that is comparable with surgery cannot be
      underestimated. Percutaneous pulmonary valve implantation uses a valved-stent
      assembly implanted by means of a double balloon catheter delivery system. The
      device is a bovine jugular venous valve sutured inside a platinum-iridium. In a
      series of 58 consecutive patients, we implanted this valve successfully with good
      clinical and hemodynamic results and no mortality on long-term follow-up. Early
      device designs led to reintervention by surgical explantation in the early
      experience, and a second percutaneous pulmonary valve implantation during latter
      experience. This exciting new technique will lead to review of the current
      indications and timing of intervention for right ventricular outflow tract
      dysfunction in late follow-up of congenital heart disease.

PMID- 16638544
TI  - Surgical management of right ventricular dysfunction late after repair of
      tetralogy of fallot: right ventricular remodeling surgery.
AB  - With the increasing number of late survivors of repair of tetralogy of Fallot,
      surgical management of patients with right ventricular (RV) dysfunction and
      limited exercise capacity has become a more frequent problem. The wide
      variability in clinical status, extent of RV dilatation, and dysfunction at the
      time of presentation for surgical intervention has resulted in disparate surgical
      results after pulmonary valve insertion. With increasing use of magnetic
      resonance imaging, quantitative measures of RV volumes, function, and pulmonary
      regurgitant fraction have enabled a more systematic analysis of results. While
      there is a group of patients that responds favorably to pulmonary valve
      insertion, there is also a large subgroup that does not; this requires further
      analysis of the mechanisms responsible. We have developed a surgical approach to
      this latter group of patients, which incorporates the concepts of ventricular
      remodeling or restoration developed for the left ventricle following myocardial
      infarction. Preliminary results indicate that this procedure is equally safe to
      pulmonary valve insertion alone, and may result in improved RV function.

PMID- 16638545
TI  - Management of sinus venosus defects.
AB  - Sinus venosus defects are not atrial septal defects, but are intra-atrial
      communications outside of the boundaries of the atrial septum. The superior type
      is located above and separate from the fossal ovalis, usually adjacent to the
      superior vena cava and the right upper pulmonary vein. The inferior type is
      located near the orifice of the inferior vena cava and the right lower pulmonary
      vein. The goal of surgical repair is closure of the defect with unobstructed
      drainage of the pulmonary veins to the left atrium and of the vena cava to the
      right atrium. Numerous techniques have been described, particularly for the
      repair of the superior vena cava type of defect. Mortality and morbidity should
      be minimal. The risk of either vena cava or pulmonary vein obstruction is low.
      Sinus node dysfunction can occur postoperatively, particularly when an incision
      has been made across the superior vena cava/right atrial junction. There is
      little long-term data on the functional outcomes following repair of these
      defects.

PMID- 16638546
TI  - Surgical repair of total anomalous pulmonary venous connection.
AB  - The diagnosis of total anomalous pulmonary venous connection (TAPVC) is made when
      all four pulmonary veins drain anomalously to the right atrium or to a tributary
      of the systemic veins. It constitutes between 1% and 1.5% of all children with
      congenital heart disease and can be categorized by the site of drainage into the
      systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed,
      5%). The clinical presentation is different if the pulmonary venous drainage is
      unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure,
      severe heart failure). Surgical management depends on the anatomic type.
      Obstructed TAPVC requires urgent surgical intervention, whereas unobstructed
      TAPVC can be dealt with electively; although this is usually operated on once the
      diagnosis is made. Postoperative pulmonary artery hypertension can be
      problematic. Recent surgical results with isolated TAPVC have improved, with
      operative mortality consistently at less than 10%. A particularly challenging
      group of patients are those with single ventricle physiology and TAPVC with high
      operative mortality and poor long-term survival.

PMID- 16638547
TI  - Surgery for pulmonary venous obstruction after repair of total anomalous
      pulmonary venous return.
AB  - The major complication and the main cause of reoperation following surgery for
      total anomalous pulmonary venous return (TAPVR) is the occurrence of pulmonary
      venous obstruction. Outcomes after surgical repair of TAPVR have greatly improved
      in the last 10 years; however, the complex forms of TAPVR, particularly when
      associated with single ventricle and heterotaxy, still carry a high risk of
      failure. The pathology of pulmonary venous obstruction following TAPVR surgery is
      a fibrous intimal hyperplasia associated with some medial hypertrophy. There is
      an increasing severity in the spectrum of lesions from anastomotic stricture to
      pulmonary vein ostial stenosis and diffuse pulmonary vein stenosis. For
      anastomotic lesions, revision of the TAPVR anastomosis by patch enlargement of
      the left atrial anastomosis provides good results. On the contrary, conventional
      techniques in cases of pulmonary vein ostial stenosis had very poor results. The
      sutureless repair technique introduced in 1996 provides better midterm results
      than any other technique, with freedom from mortality and recurrence improving
      from 65% to 90%. The sutureless technique is described in detail, with emphasis
      on the need for resection of the pulmonary vein scar tissue and on the different
      techniques needed respectively on the right and the left side. In our experience,
      using an atraumatic technique at the initial repair has greatly decreased the
      occurrence of late pulmonary venous obstruction.

PMID- 16638548
TI  - Pulmonary vein stenosis following repair of total anomalous pulmonary venous
      connection.
AB  - Pulmonary vein stenosis may occur following the repair of total anomalous
      pulmonary venous connection and carries a poor prognosis. Conventional surgical
      therapies have been complicated by a high rate of re-stenosis. Sutureless
      pericardial marsupialization has been introduced as a technique to reduce the
      rate of re-stenosis. This report describes a retrospective review of a group of
      patients undergoing repair of acquired pulmonary vein stenosis. Presence of
      single-ventricle anatomy was found to be the primary preoperative risk factor for
      a poor outcome. The use of sutureless pericardial marsupialization was found to
      be associated with a significant improvement in disease-free survival.

PMID- 16638549
TI  - Scimitar syndrome.
AB  - Scimitar syndrome is a rare congenital anomaly consisting in part of right
      pulmonary venous return to the inferior vena cava. There is a clear bimodal
      presentation of this syndrome with either an infantile manifestation or a
      pediatric/adult form. The infantile variant is marked by a higher incidence and
      severity of associated defects, heart failure, pulmonary hypertension, and
      significant mortality. The patient with the pediatric/adult form is less severely
      affected and may be asymptomatic on diagnosis. In this article, we review the
      historical aspects, presentation, and pathophysiology of Scimitar syndrome and
      discuss available treatment strategies. We emphasize the safe and effective
      approach developed at Indiana University that obviates both the need for an intra
      atrial baffle or use of cardiopulmonary bypass. The results with our alternative
      approach to Scimitar syndrome are summarized and they compare favorably with
      other published reports.

PMID- 16638550
TI  - Management of systemic venous anomalies in the pediatric cardiovascular surgical
      patient.
AB  - Systemic venous anomalies are rare and heterogeneous entities. Although these
      anomalies are rare in the general population, they occur more frequently in the
      subpopulation with congenital heart disease. In and of themselves, most of these
      lesions have no physiologic significance. However, in the setting of congenital
      heart disease these lesions may significantly alter surgical treatment. This
      review is dedicated to these lesions.

PMID- 16638551
TI  - Mechanical cardiac support in the young. Short-term support: ECMO.
AB  - Although based on technology developed several decades ago, extracorporeal
      membrane oxygenation (ECMO) retains great clinical relevance in the management of
      advanced pediatric cardiorespiratory disease. Largely because of its widespread
      use in pediatric patients with respiratory failure, familiarity with this
      technology has established ECMO as the most commonly used form of mechanical
      circulatory support in children. Clinical applications and technical aspects of
      ECMO support continue to evolve, ensuring the ongoing importance of this modality
      for pediatric circulatory support.

PMID- 16638552
TI  - Postoperative support with the centrifugal pump ventricular assist device (VAD).
AB  - Centrifugal pump left ventricular assist device is a useful adjunct in pediatric
      cardiac surgery, as a bridge to recovery, or in some cases, to transplantation.
      This form of circulatory support may not have the universal applicability of
      extracorporeal membrane oxygenation, but it is equally or more effective in
      properly selected patients. The technology for centrifugal pump support is now
      quite standardized, and the advantages well documented. In this chapter we
      discuss the problems of indications, case selection, technical aspects of the
      circuit, and general clinical management. Results since 1989 are also presented.

PMID- 16638553
TI  - The PediaFlow pediatric ventricular assist device.
AB  - The very limited options available to treat ventricular failure in patients with
      congenital and acquired heart diseases have motivated the development of a
      pediatric ventricular assist device (VAD). Our effort involves a consortium
      consisting of the University of Pittsburgh, Carnegie Mellon University,
      Children's Hospital of Pittsburgh, World Heart Corporation, and LaunchPoint
      Technologies, LLC. The overall aim of our program is to develop a highly
      reliable, biocompatible VAD for chronic support (6 months) of the unique and high
      risk population of children between 3 kg and 15 kg (patients from birth to 2
      years of age). The innovative pediatric VAD we are developing (PediaFlow) is
      based on a miniature mixed-flow turbodynamic pump featuring magnetic levitation,
      with the design goal being to assure minimal blood trauma and risk of thrombosis.
      This article discusses the limitations of current pediatric cardiac assist
      treatment options and the work to date by our consortium toward the development
      of a pediatric VAD.

PMID- 16638554
TI  - Mechanical cardiac support in the young with the Berlin Heart EXCOR pulsatile
      ventricular assist device: 15 years' experience.
AB  - The pediatric-size pneumatically driven pulsatile extracorporeal ventricular
      assist device (VAD) Berlin Heart EXCOR (Berlin Heart Mediprodukt GmbH, Berlin,
      Germany) was introduced into clinical practice by the German Heart Institute
      Berlin in 1992. Until July 1, 2005, Berlin Heart EXCOR systems have been used for
      circulatory support in 68 children up to 18 years of age with severe circulatory
      failure resistant to pharmacologic therapy. These were patients suffering from
      cardiomyopathy, fulminant myocarditis, end-stage congenital cardiac defects, and
      acute heart failure following congenital heart surgery. Mean VAD support time was
      35 days (range, 0 to 420 days). Forty-two patients (62%) survived to
      transplantation or after weaning; 37 patients (54%), including eight infants,
      were discharged home. These results in patients with very advanced disease have
      improved significantly in recent years because of technical developments and
      growing experience in the treatment of patients on the device, in postoperative
      care and optimal timing for VAD implantation. Timely implantation of the Berlin
      Heart EXCOR in the course of progressive heart failure now appears to be
      justified because the system has undergone the necessary modifications and the
      accumulation of clinical knowledge has made its use highly reliable and safe.

PMID- 16638555
TI  - Preliminary experience with the MicroMed DeBakey pediatric ventricular assist
      device.
AB  - Mechanical circulatory support for both acute and chronic heart failure is a
      widely applied therapeutic option in the adult population with a variety of
      devices clinically available. Technology in this field has advanced sufficiently
      such that long-term support or "destination therapy" has become a generally
      accepted reality. Similar progress has not occurred in the field of device
      support for heart failure in children. While the number of potential patients is
      significantly lower in the pediatric population, the clinical relevance and
      poignancy of individual need are nonetheless real. Until recently, children with
      heart failure have been largely disadvantaged in comparison to their adult
      counterparts. The DeBakey VAD Child (MicroMed Technology, Inc, Houston, TX)
      represents a hopeful initial step in the direction of reducing the technological
      gap between adults and children. While the clinical experience with this device
      is limited at present, preliminary results are encouraging. This report will
      provide an overview of the DeBakey VAD Child, including device specifications,
      indications for clinical use, surgical and postoperative considerations, and
      updated clinical experience.

PMID- 16638556
TI  - Clinical outcomes in pediatric patients implanted with Thoratec ventricular
      assist device.
AB  - Most mechanical circulatory support devices are designed for adult patients;
      however, some can be successfully applied to pediatric patients. The rates of
      complications and patient survival to transplant or native heart recovery after
      implantation of the Thoratec ventricular assist device (VAD) (Thoratec Corp,
      Pleasanton, CA) in children and adolescents were determined from the company's
      voluntary registry. As of January 2005, 209 patients (mean age 14.5 years; range
      5 to 18 years) have been supported with the Thoratec VAD. Mean patient weight was
      57 kg (range, 17 to 118 kg), and patients had a mean body surface area of 1.6 m2
      (range, 0.73 to 2.3 m2). The major etiologies necessitating VAD support included
      cardiomyopathy (55.0%), acute myocarditis (25.4%), and end-stage congenital heart
      disease (5.8%). Mean duration of VAD support was 44 days (range, 0 to 434 days).
      Patient survival to transplantation or native heart recovery was 68.4%. Patients
      with cardiomyopathy and acute myocarditis had 74.1% and 86.0% survival,
      respectively, with only 27.3% survival in patients having congenital heart
      disease. The overall survival rate in smaller children (body surface area, <1.3
      m2) was similar at 51.7%, although the incidence of congenital heart disease was
      higher.

PMID- 16638557
TI  - Mechanical devices and US Food and Drug Administration (FDA) approval.
AB  - Long-term ventricular assist devices for adults have advanced far more than have
      suitable devices for neonates and infants. The difficulties of design and
      construction of miniaturized blood pumping systems and the high costs associated
      with developing, testing, and approval of such devices has been prohibitive.
      Still, there is an important clinical need for such devices as the availability
      of donor hearts for this age group has been especially limited. Recently, several
      pneumatic pulsatile pumps have been developed based on the adult experience, and
      the issues of regulatory approval are now assuming greater importance for these
      devices. This chapter reviews the current system for medical device
      classification and the approval processes in the United States and in Europe.
      This system is continually evolving, with dedicated and knowledgeable
      professionals charged with assuring the efficacy, safety, appropriate labeling,
      and continuing surveillance of approved devices. Pediatric cardiac surgeons
      involved in transplantation and assist devices need to be aware of the regulatory
      issues, and work with manufacturers and governmental agencies to make sure that
      successful devices are available as soon as possible for their patients.

PMID- 16638558
TI  - Perioperative management of ventricular assist devices in children and
      adolescents.
AB  - Ventricular assist devices are an integral part of therapy for patients with end
      stage heart failure. Devices can either bridge to recovery or to transplantation.
      Options for ventricular assist devices include those that are centrifugal,
      pulsatile, and new rotary/axial devices. Care of the patient on a ventricular
      assist device is multifaceted, involving pharmacologic or mechanical support of
      the right ventricle, management of systemic vascular resistance, and manipulation
      of the hematologic system to avoid bleeding or thrombosis. In addition, care of
      these patients involves support of all end organs and avoidance of infectious
      complications. Care of these patients is complex, requiring a highly integrated
      team for optimal outcome.

PMID- 16638559
TI  - The morphology of ventricular septal defects as related to the mechanics
      associated with aortic regurgitation.

PMID- 16638560
TI  - Ventricular septal defect and aortic valve regurgitation: pathophysiology and
      indications for surgery.
AB  - As the velocity of a fluid increases a low-pressure zone is created, this is the
      Venturi effect and it explains the pathogenesis of aortic valve prolapse (AVP)
      and aortic insufficiency (AI) that is observed in a subset of patients with a
      ventricular septal defect (VSD). The VSDs complicated by AI are restrictive with
      high velocity shunting through the VSD, creating a low-pressure zone that impacts
      the adjacent aortic valve cusp resulting in AVP and subsequent AI. AVP and AI are
      therefore acquired lesions. AI is absent at birth because the forces necessary to
      create the low-pressure zone within the restrictive VSD do not exist in utero.
      The risk of development of AI increases during childhood, peaking at 5 to 10
      years of age. VSD closure eliminates the low-pressure zone that is the cause of
      ongoing aortic valve cusp deformity and, if performed early, prevents development
      of AI. Patients with a subarterial VSD and AVP should undergo surgery to prevent
      the development of AI because this complicates about half of subarterial VSDs
      with AVP and spontaneous closure is rare. Patients with perimembranous VSDs with
      AVP should be followed with serial echocardiography and undergo VSD closure if
      more than trivial AI develops.

PMID- 16638561
TI  - Surgical repair of infundibular ventricular septal defect and aortic
      regurgitation.
AB  - Interpretation of the anatomy of the defect and the pathophysiology has guided
      the surgical technique and indications for infundibular ventricular septal defect
      VSD. Infundibular ventricular septal defects are located in the infundibular
      septum, between the two commissures of the right coronary cusp. The defect is
      associated with an anomaly of the right sinus of Valsalva where the transition to
      cusp tissue occurs higher than normally. There is development of fibrous
      adherences between the ventricular surface of the right coronary cusp and the
      crest of the septum. This reduces the height of the cusp and destabilizes the
      valve. The aim is to reposition the hinge point of the right coronary cusp to
      restore the normal height of the cusp, hence a normal surface of apposition. This
      is achieved with a trans-aortic approach. The major difference with other
      techniques described is the extensive mobilization of the cusp. The procedure is
      completed by a reduction of the free edge of the right coronary cusp if it is
      elongated. This technique is indicated in all patients with infundibular
      ventricular septal defect in whom an aortic regurgitation appears or increases
      during follow-up. Fifteen patients were operated on with this technique between
      1996 and 2005. Thirteen have achieved good results at follow-up. There was one
      late death.

PMID- 16638562
TI  - Doubly committed subarterial ventricular septal defect with severe aortic
      regurgitation: the "two-patch" technique.
AB  - Doubly committed subarterial ventricular septal defect complicated by severe
      aortic regurgitation caused by a prolapsed aortic cusp still represents a
      challenging surgical problem. We report on our "two-patch" technique, were the
      ventricular septal defect is closed through the aortic valve by a patch anchored
      to another patch through the prolapsed cusp. This second patch is pulled up with
      the prolapsed cusp and is then fixed to the aortic wall. Since May 1990, 15
      patients with a mean age of 12 years underwent repair of this cardiac
      malformation with the "two-patch" technique. The aortic regurgitation was severe
      in all patients. All patients survived. In a mean follow-up of 10 years, two
      patients were successfully reoperated for progression of the aortic
      regurgitation. All the remaining patients were in NYHA functional class I. In
      conclusion, the "two-patch" technique is simple, easily reproducible, and can be
      a valid surgical option for this complex cardiac malformation.

PMID- 16638563
TI  - Aneurysm of the sinus of valsalva.
AB  - Aneurysms of the sinus of Valsalva (ASVs) are rare. They can be congenital or
      acquired through infection, trauma, or degenerative diseases. They frequently co
      occur with ventricular septal defects, aortic valve dysfunction, or other cardiac
      abnormalities. Although unruptured ASVs are usually asymptomatic, ruptured ASVs
      often cause symptoms similar to those of heart failure and produce a continuous,
      mechanical-sounding murmur. Transsternal or transesophageal echocardiography is
      usually effective in detecting ASVs. Because symptomatic ASVs pose significant
      risks for the patient, and because the repair of asymptomatic ASVs generally
      produces excellent outcomes, surgery is indicated in most cases. The primary
      goals of surgical repair are to close the ASV securely, remove or obliterate the
      aneurysmal sac, and repair any associated defects. Operative mortality is
      generally low except in patients with concomitant bacterial endocarditis or other
      infections. Late events are uncommon and tend to be related to aortic valve
      prothesis or Marfan syndrome.

PMID- 16638564
TI  - Surgical correction of aortico-left ventricular tunnel.
AB  - Aortico-left ventricular tunnel is a rare, paravalvular communication of unclear
      etiology between the ascending aorta and the left ventricle. The resultant
      regurgitant diastolic blood flow leads to varying degrees of volume overload and
      congestive heart failure. Diagnosis is typically made postnatally with
      echocardiography. Surgical correction is the treatment of choice consisting of
      either patch closure or primary repair of the aortic orifice. Prognosis is good,
      although a significant percentage of patients will eventually require valve
      replacement because of progressive aortic valvular insufficiency.

PMID- 16638565
TI  - Comments to water-splitting activity of photosystem II by far-red light in green
      plants.

PMID- 16638566
TI  - Kinetics and synergistic effects of siRNAs targeting structural and replicase
      genes of SARS-associated coronavirus.
AB  - SARS-associated coronavirus was identified as the etiological agent of severe
      acute respiratory syndrome and a large virus pool was identified in wild animals.
      Virus generates drug resistance through fast mutagenesis and escapes antiviral
      treatment. siRNAs targeting different genes would be an alternative for
      overcoming drug resistance. Here, we report effective siRNAs targeting structural
      genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral
      kinetics. We also showed the synergistic effects of two siRNAs targeting
      different functional genes at a very low dose. Our findings may pave a way to
      develop cost effective siRNA agents for antiviral therapy in the future.

PMID- 16638567
TI  - Annexin A8 displays unique phospholipid and F-actin binding properties.
AB  - Annexin A8 is a poorly characterized member of the annexin family of Ca2+
      regulated membrane binding proteins. Initially only identified at the cDNA level
      it had been tentatively linked to acute promyelocytic leukaemia (APL) due to its
      high and regulated expression in APL-derived cells. Here we identify unique
      properties of the annexin A8 protein. We show that it binds Ca2+-dependently and
      with high specificity to phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2)
      and is also capable of interacting with F-actin. In line with these
      characteristics annexin A8 is recruited to F-actin-associated PtdIns(4,5)P2-rich
      membrane domains formed in HeLa cells upon infection with non-invading
      enteropathogenic Escherichia coli. These properties suggest a role of annexin A8
      in the organization of certain actin-associated membrane domains.

PMID- 16638568
TI  - Identification of calconectin, a calcium-binding protein specifically expressed
      by the mantle of Pinctada margaritifera.
AB  - Nacre or mother-of-pearl in the shell of Pinctada margaritifera is composed of 95
      99% calcium carbonate and 1-5% organic matrix. In this study, we developed an
      original technique to characterize the genes differentially expressed in nacre
      forming cells (NFC) by combining suppression subtractive hybridization (SSH), to
      establish a cDNA subtractive library, with rapid amplification of cDNA ends
      (RACE)-PCR. Seventy-two specific cDNA sequences have been obtained so far. These
      include a protein containing two EF-hand Ca2+-binding domains which was
      completely sequenced after amplification by RACE-PCR. Its specific expression as
      well as the specificity of the SSH method was confirmed by semi-quantitative RT
      PCR on NFC and mantle cells.

PMID- 16638569
TI  - The evolution and diversification of Dicers in plants.
AB  - Most multicellular organisms regulate developmental transitions by microRNAs,
      which are generated by an enzyme, Dicer. Insects and fungi have two Dicer-like
      genes, and many animals have only one, yet the plant, Arabidopsis, has four.
      Examining the poplar and rice genomes revealed that they contain five and six
      Dicer-like genes, respectively. Analysis of these genes suggests that plants
      require a basic set of four Dicer types which were present before the divergence
      of mono- and dicotyledonous plants ( approximately 200 million years ago), but
      after the divergence of plants from green algae. A fifth type of Dicer seems to
      have evolved in monocots.

PMID- 16638570
TI  - Cytotoxicity of albebetin oligomers depends on cross-beta-sheet formation.
AB  - Prefibrillar cytotoxicity was suggested as a common amyloid characteristic. We
      showed two types of albebetin prefibrillar oligomers are formed during incubation
      at pH 7.3. Initial round-shaped oligomers consist of 10-15 molecules determined
      by atomic force microscopy, do not bind thioflavin-T and do not affect viability
      of granular neurons and SH-SY5Y cells. They are converted into ca. 30-40-mers
      possessing cross-beta-sheet and reducing viability of neuronal cells. Neither
      monomers nor fibrils possess cytotoxicity. We suggest that oligomeric size is
      important for stabilising cross-beta-sheet core critical for cytotoxicity. As
      albebetin was used as a carrier-protein for drug delivery, examination of
      amyloidogenicity is required prior polypeptide biomedical applications.

PMID- 16638571
TI  - New PKCdelta family members, PKCdeltaIV, deltaV, deltaVI, and deltaVII are
      specifically expressed in mouse testis.
AB  - We isolated and characterized four new PKCdelta isoforms, PKCdeltaIV, deltaV,
      deltaVI, and deltaVII, specifically expressed in the mouse testis. These isoforms
      possess neither V1 nor C2-like domains. Moreover, PKCdeltaVI and deltaVII have a
      different last exon as their V5 domain. The transcription of PKCdeltaIV, deltaV,
      deltaVI, and deltaVII is initiated from the same site in the upstream region of
      exon4 of the PKCdelta gene. They are expressed exclusively in the testis in an
      age-dependent manner. PKCdeltaIV and deltaV are expressed in spermatids with
      sperm maturation stage-specific manner, and that PKCdeltaVI and deltaVII are
      expressed in spermatogonia and spermatocytes.

PMID- 16638572
TI  - Exposure to modeled microgravity induces metabolic idleness in malignant human
      MCF-7 and normal murine VSMC cells.
AB  - We investigated the effect of modeled microgravity (MMG) on normal vascular
      smooth muscle cells (VSMC) and neoplastic human breast cancer cells (MCF-7). In
      both cell types, MMG induced partial arrest in G2M and increased p14-3-3, HSP70,
      HSP60 and p21 expression. Cells synchronized by 24h starvation reentered the
      normal cycle within 24h if released in complete medium and exposed to normal
      gravity, but not if exposed to MMG. Similarly, MMG prevented VSMC and MCF-7 cells
      from overcoming growth arrest and re-synthesizing DNA. This study shows that
      cells adjust their metabolic rate in response to MMG.

PMID- 16638573
TI  - Effect of anti-tumor ether lipids on ordered domains in model membranes.
AB  - 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (OMPC, edelfosine) and 1
      hexadecylphosphocholine (HePC, miltefosine) represent two groups of synthetic
      ether lipid analogues with anti-tumor activity. Because of their hydrophobic
      nature, they may become incorporated into plasma membranes of cells, and it has
      been argued that they may act via association with lipid rafts. With the
      quenching of steady-state fluorescence of probes preferentially partitioning into
      sterol-rich ordered domains (cholestatrienol and trans-parinaric acid), we showed
      that OMPC and HePC by themselves did not form sterol-rich domains in fluid model
      membranes, in contrast to the two chain ether lipid 1,2-O-dihexadecyl-sn-glycero
      3-phosphocholine. Nevertheless, all three ether lipids significantly stabilized
      palmitoyl-sphingomyelin/cholesterol-rich domains against temperature induced
      melting. In conclusion, this study shows that anti-tumor ether lipids are likely
      to affect the properties of cholesterol-sphingomyelin domains (i.e., lipid rafts)
      when incorporated into cell membranes.

PMID- 16638574
TI  - Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K
      binding on Gab1.
AB  - LEOPARD (LS) and Noonan (NS) are overlapping syndromes associated with distinct
      mutations of SHP-2. Whereas NS mutations enhance SHP-2 catalytic activity, we
      show that the activity of three representative LS mutants is undetectable when
      assayed using a standard protein tyrosine phosphatase (PTP) substrate. A
      different assay using a specific SHP-2 substrate confirms their decreased PTP
      activity, but also reveals a significant activity of the T468M mutant. In
      transfected cells stimulated with epidermal growth factor, the least active LS
      mutants promote Gab1/PI3K binding, validating our in vitro data. LS mutants thus
      display a reduced PTP activity both in vitro and in transfected cells.

PMID- 16638575
TI  - A single amino acid substitution on the surface of a natural hevein isoform (Hev
      b 6.0202), confers different IgE recognition.
AB  - Decreased immune reactivity of isoforms of major allergens has been reported.
      However, such claims have always been based on experiments with recombinant
      proteins. This work describes the molecular and physicochemical characterization
      of a hevein (Hev b 6.0201) natural isoform (Hev b 6.0202), which is present in
      rubber latex from Hevea brasiliensis. The isoallergen has a single substitution
      Asn14Asp, which gives rise to local differences in the surface potential, as
      observed from the crystal structure presented here. Besides, ELISA inhibition
      using serum pools of adult and pediatric patients showed reduced IgE-binding
      capacity ( approximately 27%) with the isoallergen. Overall, these results are
      relevant to delineate crucial residues involved in this dominant discontinuous
      epitope.

PMID- 16638576
TI  - Water molecules as structural determinants among prions of low sequence identity.
AB  - The nature of the factors leading to the conversion of the cellular prion protein
      (PrP(C)) into its amyloidogenic isoform (PrP(Sc)) is still matter of debate in
      the field of structural biology. The NMR structures of non-mammalian PrP(C) (non
      mPrP) from frog, chicken and turtle [Calzolai, L., Lysek, D.A., Perez, D.R.,
      Guntert, P. and Wuthrich, K. (2005) Prion protein NMR structures of chickens,
      turtles, and frogs. Proc. Natl. Acad. Sci. USA 102, 651-655] have provided some
      new and valuable information on the scaffolding elements that preserve the PrP(C)
      folding, despite their low sequence identity with the mammalian prions (mPrP).
      The present molecular dynamics study of non-mPrP(C) focuses on the hydration
      properties of these proteins in comparison with the mammalian ones. The data
      reveal new insights in the PrP hydration and focus on the implications for PrP(C)
      folding stability and its propensity for interactions. In addition, for the first
      time, a role in disfavoring the PrP(C) aggregation is suggested for a conserved
      beta-bulge which is stabilized by the local hydration.

PMID- 16638577
TI  - Visualizing cytoskeleton dynamics in mammalian cells using a humanized variant of
      monomeric red fluorescent protein.
AB  - Fluorescent proteins are versatile tools for live cell imaging studies. In
      particular, recent progress was achieved in the development of monomeric red
      fluorescent proteins (mRFPs) that show improved properties in respect to
      maturation and intracellular fluorescence. mRFPmars, a red fluorescent protein
      designed especially for the use in Dictyostelium, proved to be a brilliant label
      for different cytoskeletal elements. Here we report on the synthesis of a
      humanized version of a monomeric RFP, mRFPruby, which differs in sequence from
      mRFPmars in four amino acids and has a codon usage that is optimized for the
      application in mammalian cells. In order to demonstrate the usefulness of this
      new mRFP variant, mRFPruby fused to beta-actin was expressed in different mouse
      cell lines and used to visualize actin cytoskeleton dynamics by live cell
      microscopy.

PMID- 16638578
TI  - The involvement of glycogen synthase kinase-3 and protein phosphatase-2A in
      lactacystin-induced tau accumulation.
AB  - Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in
      HEK293 cells stably expressing tau. Simultaneously, it induces accumulation of
      both non-phosphorylated and hyperphosphorylated tau and decreases the binding of
      tau to the taxol-stabilized microtubules. Lactacystin activates glycogen synthase
      kinsase-3 (GSK-3) and decreases the phosphorylation of GSK-3 at serine-9. LiCl
      inhibits GSK-3 and thus reverses the lactacystin-induced accumulation of the
      phosphorylated tau. Lactacystin also inhibits protein phosphase-2A (PP-2A) and it
      significantly increases the level of inhibitor 1 of PP-2A. These results suggest
      that inhibition of proteasome by lactacystin induces tau accumulation and
      activation of GSK-3 and inhibition of PP-2A are involved.

PMID- 16638579
TI  - Differential involvement of ERK1-2 and p38MAPK activation on Swiss 3T3 cell
      proliferation induced by prostaglandin F2alpha.
AB  - Prostaglandin F2alpha (PGF2alpha) induces cyclin D1 expression and DNA synthesis
      in Swiss 3T3 cells. In order to assess which signaling mechanisms are implicated
      in these processes, we have used both a pharmacological approach and interfering
      mutants. We demonstrate that PGF2alpha induces extracellular-signal-regulated
      kinase (ERK1-2) and p38MAPK activation, and inhibition of any of these signaling
      pathways completely blocks PGF2alpha-stimulated DNA synthesis. We also show that
      ERK1-2, but not p38MAPK activation is required to induce cyclin D1 expression,
      strongly suggesting that the concerted action of cyclin D1 gene expression and
      other events are required to induce complete phosphorylation of retinoblastoma
      protein and S-phase entry in response to PGF2alpha.

PMID- 16638580
TI  - Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS)
      and TNF-alpha mRNA expression in human monocytes by allicin.
AB  - Chronic inflammation associated with tumor necrosis factor (TNF)-alpha and
      reactive oxygen species (ROS) is the hallmark of tuberculosis. Mycobacterium
      tuberculosis (MTB) directly stimulates human monocytes to secrete TNF-alpha. We
      show the augmented expression of TNF-alpha mRNA in MTB-infected monocytes by
      cellular activation and ROS was suppressed by allicin in a dose-dependent manner.
      Also, allicin enhanced the glutathione peroxidase activity, which correlated
      inversely with the downregulation of ROS and TNF-alpha in MTB-infected monocytes.
      Hence, allicin may prove to be a valuable natural antioxidant in combating
      tuberculosis.

PMID- 16638581
TI  - Inhibition of platelet-derived growth factor-induced mesangial cell proliferation
      by cyclooxygenase-2 overexpression is abolished through reactive oxygen species.
AB  - Proliferation of mesangial cells (MC) is an early event in many forms of
      glomerulonephritis. We have previously shown that platelet-derived growth factor
      (PDGF)-induced proliferation of MC was inhibited by the overexpression of
      cyclooxygenase-2 (COX-2). Since reactive oxygen species (ROS) are important
      mediators of mitogenic signaling, we evaluated the role of ROS in the COX-2
      induced growth arrest in MC. We demonstrate that ROS are reduced in COX-2
      overexpressing MC. Intracellular elevation of ROS restored PDGF-induced
      proliferation, while the expression of the cyclin-dependent kinase inhibitors
      p21(cip1) and p27(kip1) were decreased in these cells. The data suggest that COX
      2 decreases ROS formation which consequently leads to the PDGF-induced inhibition
      of MC proliferation.

PMID- 16638583
TI  - Alternatives to land disposal.

PMID- 16638584
TI  - Nuchal translucency and first-trimester screening.

PMID- 16638585
TI  - The mitogen-activated protein kinases and Akt are developmentally regulated in
      the chronically anemic fetal sheep heart.
AB  - OBJECTIVE: Protein kinase B (Akt) and the mitogen-activated protein kinases
      (MAPKs) mediate hypertrophy in the adult heart, although their importance in the
      developing heart is poorly understood. The goal of the current study was to
      determine if volume loading the fetal heart resulting from chronic anemia affects
      regulation of Akt and the MAPKs and if this response is developmentally
      regulated. METHODS: Anemia was created by 7 days of isovolumic hemorrhage
      beginning at 101 days (early GA) or 129 days (late GA) gestational age (GA) in
      fetal sheep (term = 145 days), following which protein levels of total and active
      Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal
      kinase (JNK), and p38 were determined in the right and left ventricle (RV and
      LV). RV protein-to-DNA ratios were also assessed. RESULTS: At both GAs,
      ventricular (RV + LV + septum) weight normalized to body weight was significantly
      increased in anemic fetuses. Anemia had no effect on expression of myocardial
      total or active Akt, JNK, or p38 at either GA. Levels of total ERK1/2 were also
      unchanged, although active ERK1/2 was significantly decreased in the late but not
      early GA anemic fetuses. Total JNK and total and active ERK1/2 and Akt were
      significantly greater in early versus late GA anemic fetuses. Protein-to-DNA
      ratios were unchanged in response to anemia at both GAs, but were greater in late
      GA compared to early GA anemic fetuses. CONCLUSION: These results identify
      important developmental differences in the response of the MAPKs and Akt in the
      stressed fetal heart. Differences in protein-to-DNA ratios likely reflect the
      different populations of cardiomyocytes composing the fetal heart at these two
      GAs and their cell-dependent response to a hemodynamic load.

PMID- 16638586
TI  - Changes in umbilical arterial blood flow by an intraamniotic distilled water
      infusion.
AB  - OBJECTIVES: The purpose is to investigate how umbilical arterial blood flow
      changes by an intraamniotic distilled water infusion and to determine whether the
      changes in umbilical circulation have any relationship with fetal cardiovascular
      status and osmolality in amniotic fluid and fetal plasma. METHODS: Eleven
      chronically catheterized pregnant sheep were used in this study. After a 1-hour
      control period, 1.5 L of warmed sterile distilled water was injected over 10
      minutes into the amniotic cavity. Fetal heart rate and carotid arterial pressure,
      blood flow of the umbilical and fetal carotid arteries were continuously
      measured. Fetal arterial blood sampled twice during the control period and then
      at 30, 60, 90, 120, 180, 240, 300, and 360 minutes after the start of the
      infusion, was analyzed for blood gases, pH, plasma electrolytes, and osmolality.
      RESULTS: Data obtained from seven sheep with normoxemic fetuses were studied
      statistically. Umbilical arterial blood flow decreased significantly from 229.5
      +/- 3.83 mL/min in the control to 167.4 +/- 11.1 mL/min at 30 minutes after water
      infusion (P < .001). Umbilical arterial vascular resistance increased rapidly and
      reached its peak at approximately 60 minutes after infusion and then showed a
      gradual recovery to the control level (P < .001). Amniotic fluid osmolality had a
      high degree of correlation with umbilical arterial blood flow and vascular
      resistance, while fetal arterial blood pressure and heart rate had only little
      correlation with umbilical blood flow. CONCLUSION: A distilled water infusion
      into the amniotic cavity in near-term pregnant sheep led to an acute drop in
      umbilical arterial blood flow. The changes in umbilical flow were closely
      correlated with those in amniotic fluid osmolality. Hemolysis in the capillary
      networks in the fetal membranes seems to be one of the main causes of umbilical
      vasoconstriction. It is speculated that the fetal membranes, including capillary
      networks, intramembranous pathway, and amnion epithelial cells, sense the changes
      in amniotic fluid osmolality, which leads to a fetal adaptation to the hypotonic
      environment.

PMID- 16638587
TI  - Acute and long-term effects of clinical doses of antenatal glucocorticoids in the
      developing fetal sheep kidney.
AB  - OBJECTIVES: The controversy regarding potential long-term side effects of
      antenatal steroid administration for accelerating fetal lung maturation is still
      unresolved despite more than 30 years of experience. Studies in animals have
      demonstrated that administration of glucocorticoids during pregnancy alters renal
      expression of several key regulatory molecules at different developmental stages
      followed in most cases with the development of hypertension in the adult. We
      studied the effects of betamethasone on the expression of (1) NA,K-ATPAse pump;
      (2) the Na/H exchanger 3 (NAHE3); (3) angiotensin receptor (AT1 and AT2); and (4)
      the type 1 dopamine receptor (D1R). METHODS: Pregnant sheep were treated with
      either 0.17 mg/kg betamethasone or vehicle 24 hours apart at 80 and 81 days'
      gestation. Fetal kidneys were harvested at 81 and 135 days' gestation. Protein
      and mRNA levels were measured in kidney cortex. RESULTS: Betamethasone had acute
      and long-term effects on fetal kidney cortex gene expression. Acutely, mRNA
      abundance for AT2 was significantly lower and that of NHE3 significantly higher
      than in controls (0.4 +/- 0.02 vs 0.7 +/- 0.05; 1.2 +/- 0.16 vs 0.4 +/- 0.04; P <
      .05). At 135 days' gestation, AT2 receptor abundance remained lower than control
      (0.2 +/- 0.02 vs 0.4 +/- 0.02; P < .05), whereas D1R expression was higher (0.8
      +/- 0.17 vs 0.5 +/- 0.06; P < .05). No changes in Na,K-ATPase of AT1 receptor at
      either of the two time points studied were observed. Antenatal steroid
      administration was not associated with premature labor or a reduction in either
      body weight or kidney weight. CONCLUSION: Our findings strongly suggest that
      antenatal glucocorticoid administration according to National Institutes of
      Health (NIH) consensus guidelines may alter human fetal renal development.
      Further studies are needed to establish a direct relationship between alterations
      in fetal renal gene expression and the development of hypertension in adulthood.

PMID- 16638588
TI  - Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic
      adenosine monophosphate in amnion epithelial cell culture.
AB  - OBJECTIVE: The cell membrane water channel protein aquaporins (AQPs) may be
      important in regulating the intramembranous (IM) pathway of amniotic fluid (AF)
      resorption. The objective of the present study was to determine whether aquaporin
      3 (AQP3) is expressed in human fetal membranes and to further determine if AQP3
      expression in primary human amnion cell culture is regulated by second-messenger
      cyclic adenosine monophosphate (cAMP). METHODS: AQP3 expression in human fetal
      membranes of normal term pregnancy was studied by reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). To determine
      the effect of cAMP on AQP3 expression, primary human amnion cell cultures were
      treated in either heat-inactivated medium alone (control), or heat-inactivated
      medium containing: (1) SP-cAMP, a membrane-permeable and phosphodiesterase
      resistant cAMP agonist, or (2) forskolin, an adenylate cyclase stimulator. Total
      RNA was isolated and multiplex real-time RT-PCR employed for relative
      quantitation of AQP3 expression. RESULTS: We detected AQP3 expression in
      placenta, chorion, and amnion using RT-PCR. Using IHC, we identified AQP3 protein
      expression in placenta syncytiotrophoblasts and cytotrophoblasts, chorion
      cytotrophoblasts, and amnion epithelia. In primary amnion epithelial cell
      culture, AQP3 mRNA significantly increased at 2 hours following forskolin or SP
      cAMP, remained elevated at 10 hours following forskolin, and returned to baseline
      levels by 20 hours following treatment. CONCLUSION: This study provides evidence
      of AQP3 expression in human fetal membranes and demonstrates that AQP3 expression
      in primary human amnion cell culture is up-regulated by second-messenger cAMP. As
      AQP3 is permeable to water, urea, and glycerol, modulation of its expression in
      fetal membranes may contribute to AF homeostasis.

PMID- 16638589
TI  - Elevated mid-trimester amniotic fluid ADAM-8 concentrations as a potential risk
      factor for preterm delivery.
AB  - OBJECTIVE: To determine during mid-trimester amniocentesis if elevated
      concentrations of ADAM-8 (A Disintegrin And Metalloprotease 8) and/or cortisol
      can recognize women at risk for spontaneous preterm delivery. METHODS: The study
      involved 312 women who underwent mid-trimester amniocentesis. Thirteen patients,
      who progressed to preterm delivery, were matched with 21 controls for age,
      parity, gestational age at amniocentesis, and year of amniocentesis. ADAM-8 and
      cortisol levels were measured by enzyme-linked immunosorbent assay and
      radioimmunoassay, respectively. RESULTS: ADAM-8 mean amniotic fluid
      concentrations were significantly higher in women with preterm delivery than in
      women delivering at term (mean 1213.9 [SE 96.7] pg/mL [range, 780 to 1854 pg/mL]
      vs mean 937.2 [SE 50.3] pg/mL [range, 486 to 1508 pg/mL], P < .02). Amniotic
      fluid ADAM-8 concentrations higher than 1149 pg/mL had the highest specificity
      and odds ratio (OR) in the identification of the women with increased risk for
      preterm delivery (sensitivity 61.5%; specificity 81.7%; OR, 9.6 [95% confidence
      interval (CI), 1.8 to 50.3]). Women with preterm delivery had suggestively higher
      amniotic fluid concentrations of cortisol (mean 1.3 [SE 0.2] microg/dL [range,
      0.4 to 2.2 microg/dL]) than women delivering at term (mean 1.0 [SE 0.09]
      microg/dL [range, 0.6 to 1.7 microg/dL], P < .07). Furthermore, cortisol levels
      were positively correlated with ADAM-8 levels (Spearman's r = .418, P < .014).
      CONCLUSIONS: Elevated mid-trimester amniotic fluid ADAM-8 concentrations possibly
      are a risk factor for preterm delivery, particularly if ADAM-8 levels are greater
      than 1149 pg/mL. Potential intrauterine inflammation is also associated with
      suggestively increased amniotic fluid cortisol levels.

PMID- 16638590
TI  - Fetal membranes from term vaginal deliveries have a zone of weakness exhibiting
      characteristics of apoptosis and remodeling.
AB  - BACKGROUND: Recently we identified a weak zone in term, pre-labor (repeat
      Cesarean section) human fetal membranes (FM) overlying the cervix with
      biochemical characteristics suggestive of apoptosis and collagen remodeling. We
      suggested that this weak zone is the FM rupture initiation site. Vaginally
      delivered patients have a weak zone in their FM overlying the cervix; a
      comparable weak zone lies adjacent to the tear line in FM after spontaneous
      rupture (SROM). METHODS: FM from vaginally delivered patients with artificial
      rupture (AROM) and SROM were collected. FM of AROM patients were marked per
      vagina to identify the FM zone overlying the cervix. Postpartum FM were cut,
      strength tested, and piece strengths were remapped to their former location on a
      three-dimensional model. A 10-cm diameter zone centered on the marked area
      (AROM), or defined weak zone (SROM) was compared with the remaining FM. RESULTS:
      AROM FM exhibit a para-cervical weak zone. SROM FM exhibit a comparable zone on
      the tear line. The mean rupture strength within weak zones was 60% of the
      remaining membranes (P <.001). AROM and SROM FM weak zones both exhibit increased
      matrix metalloproteinase 9, increased poly (ADP-ribose) polymerase I cleavage,
      decreased tissue inhibitor of metalloproteinase 3 protein, and histology
      consistent with remodeling and apoptosis. CONCLUSION: Vaginally delivered AROM FM
      contain a weak zone overlying the cervix. Vaginally delivered SROM FM contain a
      weak zone adjacent to the tear line that exhibits biochemical and mechanical
      characteristics suggestive of collagen remodeling and apoptosis comparable to
      those of the AR FM weak zone.

PMID- 16638591
TI  - Changes in cervical nitric oxide concentration correlate with Bishop score and
      cervical length modifications in prostaglandin E2-mediated induction of labor.
AB  - OBJECTIVE: Nitric oxide (NO) plays a fundamental role in cervical ripening and it
      is synthesized in the human cervix. We studied the effect of the dinoprostone on
      cervical NO release in pregnant women, and we investigated the relationship
      between cervical NO metabolites, cervical length, and Bishop score. METHODS:
      Seventy-seven women underwent induction of labor at > or = 37 weeks of gestation,
      due to post-term pregnancy (23.8%), oligohydramnios (36.3) or preeclampsia
      (29.9%). Cervical fluid samples for NO metabolites (NOx), Bishop score, and
      cervical length were assessed immediately before (time 0 [T0]) and 6 hours after
      (T6) the local application of dinoprostone, a commercially available
      prostaglandin E2 (PGE2) analog. RESULTS: The mean patients' age was 34 +/- 3.2
      years, mean gestational age at enrollment was 284 +/- 9.2 days, and nulliparous
      represented 31.2% of the study population. At time 0, Bishop score was less than
      4 in 74% (57/77) of the subjects, mean cervical length was 28.6 +/- 5.8 mm, mean
      NOx concentration was 208.6 +/- 103.8 microM/mL; 6 hours later, at T6, the mean
      cervical length decreased to 19.5 +/- 8.8 mm, and the mean NOx concentration
      increased up to 316.7 +/- 240.9 microM/mL. Data were unaffected by parity or by
      regular uterine contraction patterns. A statistically significant positive
      correlation was found between changes in cervical NOx levels and Bishop score
      modification (P < .01; r = .494), as well as between the modification of NO
      metabolites concentration and cervical shortening (P < .01; r = .307).
      CONCLUSIONS: Prostaglandin (PG)-induced cervical ripening is associated with
      local NO release. NO plays an active role in cervical remodeling since it
      positively correlates with both cervical shortening and Bishop score increase. NO
      oxide and PG are the two pathways that, cross activating each other, trigger the
      cascade of events responsible of cervical ripening.

PMID- 16638592
TI  - Nuchal edema and venous-lymphatic phenotype disturbance in human fetuses and
      mouse embryos with aneuploidy.
AB  - OBJECTIVE: Nuchal edema (NE) is a clinical indicator for aneuploidy,
      cardiovascular anomalies, and several genetic syndromes. Its etiology, however,
      is unknown. In the nuchal area, the endothelium of the jugular lymphatic sacs
      (JLS) develops by budding from the blood vascular endothelium of the cardinal
      veins. Abnormal distension of the jugular sacs is associated with NE. We
      hypothesize that a disturbed lymphatic endothelial differentiation and sac
      formation causes NE. We investigated endothelial differentiation of the jugular
      lymphatic system in human and mouse species with NE. METHODS: Aneuploid human
      fetuses (trisomy 21; trisomy 18) were compared with euploid controls (gestational
      age 12 to 18 weeks). Trisomy 16 mouse embryos were compared with wild type
      controls (embryonic day 10 to 18). Trisomy 16 mice are considered an animal model
      for human trisomy 21. Endothelial differentiation was investigated by
      immunohistochemistry using lymphatic markers (prox-1, podoplanin, lymphatic
      vessel endothelial hyaluronan receptor [LYVE]-1) and en blood vessel markers
      (neuropilin [NP]-1 and ligand vascular endothelial growth factor [VEGF]-A).
      Smooth muscle actin (SMA) was included as a smooth muscle cell marker. RESULTS:
      We report a disturbed venous-lymphatic phenotype in aneuploid human fetuses and
      mouse embryos with enlarged jugular sacs and NE. Our results show absent or
      diminished expression of the lymphatic markers Prox-1 and podoplanin in the
      enlarged jugular sac, while LYVE-1 expression was normal. Additionally, the
      enlarged JLS showed blood vessel characteristics, including increased NP-1 and
      VEGF-A expression. The lumen contained blood cells and smooth muscle cells lined
      the wall. CONCLUSION: A loss of lymphatic identity seems to be the underlying
      cause for clinical NE. Also, abnormal endothelial differentiation provides a link
      to the cardiovascular anomalies associated with NE.

PMID- 16638593
TI  - Matrix metalloproteinase-1 and -9 promoter polymorphisms are not associated with
      an increased risk of uterine leiomyomas in a Japanese population.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) play an important role in modeling
      and remodeling the extracellular matrix in leiomyomas. Hence, we investigated
      whether associations exist between leiomyomas and promoter polymorphisms in the
      MMP-1 and MMP-9 genes in a Japanese population. METHODS: We compared the
      distribution of polymorphisms in the promoter regions of MMP-1 (-1607 1G/2G) and
      MMP-9 (-1562 C/T) in 267 leiomyoma patients and 184 control patients using
      polymerase chain reaction-fragment-length polymorphism (PCR-RFLP) analysis.
      RESULTS: The allele frequencies of the MMP-1 -1607 2G and MMP-9 -1562 T
      polymorphisms were 74.6% and 18.6% in leiomyoma patients, and 71.3% and 18.6% in
      control patients, respectively. No significant differences in allele frequencies
      or genotype distributions were found between leiomyoma and control patients.
      Moreover, no associations were found between MMP-1 and MMP-9 genotypes and
      leiomyoma size or a family history of the condition. CONCLUSION: These findings
      suggest that MMP-1 and MMP-9 promoter polymorphisms are unlikely to be associated
      with an increased risk of uterine leiomyomas in Japanese women.

PMID- 16638595
TI  - But what about men?

PMID- 16638596
TI  - Is there evidence for the evidence-based guidelines for cardiovascular disease
      prevention in women?

PMID- 16638597
TI  - Pharmacist refusals: a new twist on the debate over individual autonomy.

PMID- 16638598
TI  - Turner's syndrome and X chromosome-based differences in disease susceptibility.

PMID- 16638599
TI  - Gender-related differences in dyspepsia: a qualitative systematic review.
AB  - BACKGROUND: Relative to men, women are diagnosed more frequently with functional
      gastrointestinal (GI) disorders. With increased awareness of basic gender
      differences in perception and treatment of visceral pain, there has been new
      interest in research on gender disparity in the care of people with functional GI
      disorders. Past attention has focused on irritable bowel syndrome, whereas gender
      differences in other disorders are less well described. OBJECTIVE: Our aim was to
      systematically review studies that have examined gender-related differences among
      patients with dyspepsia. METHODS: MEDLINE, HealthSTAR, and PsycINFO databases
      were searched for English-language articles on dyspepsia published between 1966
      and August 2001. Epidemiologic studies, clinical trials, review articles, and
      conceptual articles from peer-reviewed journals were included for review.
      Findings were summarized and discussed within a framework of biological and
      psychosocial factors. Statistical analysis of combined data was inappropriate
      because of the inconsistent definition of dyspepsia among different studies and
      wide variation in the types of articles reviewed. RESULTS: Studies that examine
      gender-related differences in patients with dyspepsia have focused their
      investigations on the clinical epidemiology and pathophysiology of dyspepsia. In
      most epidemiologic studies, no gender analysis was performed beyond a description
      of sample demographics, and when statistical significance was tested, few
      consistent gender differences were found. Overall, it appears that men and women
      with dyspepsia possibly differ with respect to pattern of symptoms, pain
      perception or modulation, and antinociceptive mechanisms, but these observations
      have not been confirmed. No study evaluated the clinical implications of these
      possible differences. CONCLUSIONS: Future efforts should be directed to not only
      examine gender-related differences in the clinical epidemiology of dyspepsia, but
      also understand their clinical significance. Therefore, well-designed population
      based studies using a consistent definition of dyspepsia are needed to
      investigate the prevalence of dyspepsia symptoms and patterns of dyspepsia
      management among men and women.

PMID- 16638600
TI  - Estrogens contribute to a sex difference in plasma potassium concentration: a
      mechanism for regulation of adrenal angiotensin receptors.
AB  - BACKGROUND: The adrenal mineralocorticoid aldosterone promotes sodium (Na(+))
      reabsorption and potassium (K(+)) loss from the kidney. Female sex steroids such
      as estrogen and progesterone are known modulators of the renin-angiotensin
      aldosterone system. OBJECTIVE: We conducted studies to determine if there is a
      sex difference in plasma Na(+) concentration ([Na(+)]) and plasma K(+)
      concentration ([K(+)]), and if interactions between female sex steroids and
      aldosterone contribute to a sex difference in these electrolytes. METHODS: Plasma
      [Na(+)] and [K(-)] were determined in weight-matched male and female Sprague
      Dawley rats using an ion-selective electrode system. To assess the sensitivity of
      males and females to aldosterone, the mineralocorticoid was infused chronically
      by osmotic minipump. The role of female sex steroids in the regulation of plasma
      electrolyte concentrations was determined in bilaterally ovariectomized (OVX)
      female rats treated daily with SC injections of progesterone, 17beta-estradiol
      (E(2)), or selective estrogen receptor (ER) modulators. The role of plasma [K(+)]
      in the regulation of adrenal angiotensin II type 1 receptor (AT(1)R) expression
      was determined by manipulating plasma [K(+)] by varying dietary K(-). Adrenal
      AT(1)R expression was assessed using a radioligand binding assay. RESULTS: Plasma
      [Na(-)] was not different between male and female rats, but plasma [K(-)] was
      reduced in females compared with males (P = 0.003). In aldosterone-infused female
      rats, plasma [Na(+)] was increased and plasma [K(+)] was reduced further than in
      male rats infused with aldosterone (both, P = 0.001). In OVX female rats,
      progesterone reduced plasma [Na(+)] (P = 0.04) but had no effect on plasma
      [K(+)]. In contrast, E(2) increased plasma [Na(+)] (P = 0.01) and reduced plasma
      [K(+)] (P = 0.001). Dietary K supplementation in E(2)-treated rats returned
      plasma [K(+)] and adrenal AT(1)R binding to levels observed in control rats. Both
      an ERa and ERP agonist decreased plasma [K(+)] and decreased adrenal AT(1)R
      binding (both, P < 0.01). CONCLUSIONS: In these studies, plasma [K(+)] was
      reduced in female Sprague-Dawley rats compared with males. The effects of
      aldosterone on plasma electrolytes were enhanced in females compared with males.
      E(2) treatment reduced plasma [K(+)] and adrenal AT(1)R binding in OVX rats, and
      the decrease in plasma [K(+)] contributed to the decrease in adrenal AT(1)R
      binding. Both ERalpha and ERbeta contributed to the estrogen-induced decrease in
      plasma [K(+)] and adrenal AT(1)R binding.

PMID- 16638601
TI  - Gender disparities in posttraumatic stress disorder after mass trauma.
AB  - BACKGROUND: Although several studies have shown that rates of posttraumatic
      stress disorder (PTSD) are higher in women than in men, less is known about
      whether women are more vulnerable to PTSD after a major community-wide traumatic
      event. OBJECTIVE: The aim of this study was to examine gender disparities in the
      prevalence of probable lifetime PTSD and probable PTSD after a mass traumatic
      event. METHODS: A representative sample of men and women living in the New York
      City metropolitan area was selected using random-digit dialing, and subjects were
      interviewed by telephone 6 to 9 months after the September 11, 2001 (9/11)
      terrorist attacks. We assessed probable lifetime PTSD and probable PTSD related
      to the 9/11 attacks using a brief screening instrument and potential correlates.
      RESULTS: A total of 2752 individuals (1479 women, 1273 men) were interviewed. The
      lifetime prevalence of probable PTSD was significantly higher for women than for
      men (17.2% vs 12.1%; P = 0.005). Experiences of sexual assault (P < 0.001),
      preexisting mental health problems (P = 0.04), race/ethnicity (P = 0.01), marital
      status (P < 0.001), and having had probable peri-event panic in the first few
      hours after the 9/11 attacks (P < 0.001) were all significantly related to
      women's greater susceptibility to probable lifetime PTSD. However, the prevalence
      of probable PTSD related to 9/11 was not significantly different between women
      and men (6.5% vs 5.4%), although women were significantly more likely to report
      re-experiencing (P < 0.001) and hyperarousal (P < 0.001) symptoms than were men.
      Women were more likely than men to experience probable peri-event panic during
      the 9/11 attacks (P < 0.001); this explained, in part, the greater subsequent
      likelihood of re-experiencing and hyperarousal symptoms among women compared with
      men. CONCLUSIONS: More factors explain the risk of PTSD among women and men after
      interpersonal trauma than after a disaster. Using peri-event panic symptomatology
      after a traumatic event to determine the risk of posttraumatic symptoms may
      suggest avenues for intervention that can decrease the burden of PTSD in women.

PMID- 16638602
TI  - Hyperbaric oxygen therapy reduces the size of Leishmania amazonensis-induced soft
      tissue lesions in mice.
AB  - In this study we determined whether exposing mice to hyperbaric oxygen (HBO)
      would alter various disease parameters of a susceptible mouse strain infected
      with Leishmania amazonensis. BALB/c mice exposed to HBO (100% O2 at a pressure of
      2.5 ATA, 1h before parasite inoculation and subsequently for 20 days) showed
      significant delay in lesion development and reduction in lesion parasite burdens
      compared with HBO-unexposed mice. Circulating levels of interferon gamma (IFN
      gamma) and tumor necrosis factor (TNF-alpha) were significantly elevated in HBO
      exposed as compared to HBO-unexposed mice. Concanavalin A-stimulated lymph nodes
      cultures from HBO-exposed mice released significantly more IFN-gamma and less
      interleukin 10 (IL-10) than cultures from HBO-unexposed mice, consistent with a
      skewed Th1 response. These results demonstrate, for the first time, that HBO can
      play a pathogen control role during leishmaniasis. Further studies are needed to
      elucidate whether hyperoxia alone or increased atmospheric pressure alone can
      exert a similar effect.

PMID- 16638603
TI  - Detection of gestational diabetes mellitus by homeostatic indices of insulin
      sensitivity: a preliminary study.
AB  - OBJECTIVE: We investigated whether homeostatic indices of insulin sensitivity
      might suitably screen for gestational diabetes mellitus. STUDY DESIGN: One
      hundred twenty-three pregnant women who were between 24 and 28 weeks of gestation
      completed a 3-hour 100-g oral glucose challenge test and fasting insulin level in
      a nested case-control study design. Insulin sensitivity indices were calculated
      and tested for their ability to detect gestational diabetes mellitus. RESULTS:
      Fasting glucose demonstrated the best overall accuracy, but the homeostasis model
      assessment and quick insulin sensitivity check index were also sensitive
      screening techniques for gestational diabetes mellitus when either the National
      Diabetes Data Group or Carpenter-Coustan criteria were used. CONCLUSION:
      Homeostasis model assessment, quick insulin sensitivity check index, and fasting
      glucose are sensitive screening tests for gestational diabetes mellitus and can
      avoid oral administration of glucose-containing solutions.

PMID- 16638604
TI  - High-frequency conditioning electrical stimulation evokes supraspinal independent
      long-term depression but not long-term potentiation of the spinal withdrawal
      reflex in rats.
AB  - The aim of the current study was to investigate the effects on the spinal
      withdrawal reflex of electrical stimulation that has been shown to induce long
      term potentiation (LTP) in spinal sensory systems. This was done in order to
      enhance our understanding of long-term dynamic modifications of spinal motor
      system during the exposure to high-frequency conditioning electrical stimulation
      (cES). The spinal withdrawal reflex was assessed by extracellular recording of
      the single motor unit (SMU) electromyographic (EMG) activity from the medial
      gastrocnemius (MG) muscle in intact and acutely spinalized rats. High-frequency
      (1 ms pulses at 100 Hz for 2 s repeated three times at 10 s intervals) tetanic
      cES produced a significant long-term depression (LTD) (at least 3 h), but not
      LTP, of the electrically evoked SMU EMG activity as well as the wind-up
      phenomenon (temporal summation). There were no significant depressive or
      facilitatory effects of low-frequency (2 Hz) cES, consisting of the same number
      of pulses as the 100 Hz cES, on the SMU EMG responses. This frequency-dependent
      long-term depressive effect on the spinal withdrawal reflex was not significantly
      changed following acute spinalization, indicating that LTD of the spinal motor
      system elicited by high-frequency cES is independent of the descending control
      system. We conclude that, in contrast to LTP in spinal sensory systems to brief
      tetanic C-fiber cES, high-frequency cES seems only to elicit LTD of motor systems
      of the spinal cord.

PMID- 16638605
TI  - Distribution of urocortin 3 neurons innervating the ventral premammillary nucleus
      in the rat brain.
AB  - Urocortin 3 (Ucn 3) is a recently described peptide of the corticotropin
      releasing factor family. Neurons expressing Ucn 3 mRNA and peptide are
      distributed in specific brain areas, including the median preoptic nucleus, the
      perifornical area (PFx), and the medial nucleus of the amygdala (MEA). Fibers
      immunoreactive to Ucn 3 are confined to certain brain nuclei, being particularly
      dense in the ventral premammillary nucleus (PMV). In studies involving
      electrolytic lesions and analysis of Fos distribution according to behavioral
      paradigms, the PMV has been potentially implicated in conspecific aggression and
      sexual behavior. However, the role that Ucn 3 plays in this pathway has not been
      explored. Therefore, we investigated the origins of the urocortinergic
      innervation of the PMV of Wistar rat in an attempt to map the brain circuitry and
      identify likely related functions. We injected the retrograde tracer cholera
      toxin b subunit into the PMV and found that 88% of the Ucn 3-immunoreactive
      fibers in the PMV originate in the dorsal MEA, and that few originate in the PFx.
      As a control, we injected the anterograde tracer biotin dextran amine into both
      regions. We observed that the PMV is densely innervated by the MEA, and scarcely
      innervated by the PFx. The MEA is a secondary relay of the vomeronasal system and
      projects amply to hypothalamic nuclei related to hormonal and behavioral
      adjustments, including the PMV. Although physiological studies should also be
      performed, we hypothesize that Ucn 3 participates in such pathways, conveying
      sensory information to the PMV, which in turn modulates behavioral and
      neuroendocrine responses.

PMID- 16638606
TI  - Amphetamine-induced disruption of prepulse inhibition in mice with reduced NMDA
      receptor function.
AB  - Genetically altered mice with reductions in the NR1 subunit of the N-methyl-d
      aspartate (NMDA) receptor have been proposed as a model for the intrinsic NMDA
      hypofunction hypothesized for schizophrenia. The following study investigated
      whether NR1-deficient mice have enhanced susceptibility for the effects of
      amphetamine, similar to the exaggerated responsivity to dopamine agonists
      observed in many schizophrenia patients. NR1-/- mice and wild-type controls were
      tested for the effects of amphetamine (2-10 mg/kg) on prepulse inhibition of
      acoustic startle responses. The results showed that mice with reduced NMDA
      receptor function demonstrated consistent deficits in prepulse inhibition (PPI),
      as well as higher startle response amplitudes. In comparison to normal controls,
      the NR1-/- mice were more sensitive to the disruptive effects of amphetamine on
      PPI, but not to the drug effects on startle magnitude without a prepulse
      stimulus. Wild-type mice only showed decreased PPI at the highest dose of
      amphetamine tested (10 mg/kg) and demonstrated small increases in PPI at lower
      amphetamine doses (2 and 6 mg/kg). The NR1-/- mice did not show enhanced PPI in
      response to amphetamine at low doses, with reductions in PPI apparent at doses of
      4-10 mg/kg. Overall, these findings suggest that the NR1-/- mouse may provide a
      model for enhanced sensitivity to dopamine agonist-induced disruption of PPI.

PMID- 16638607
TI  - Hemicerebellectomy impairs the modulation of cutaneomuscular reflexes by the
      motor cortex following repetitive somatosensory stimulation.
AB  - We examined the cutaneomuscular reflex of the plantaris muscle of rats in
      response to cutaneous stimulation in isolation and in conjunction with
      subthreshold high-frequency trains of stimuli applied on the motor cortex, prior
      to and following repetitive peripheral stimulation. The cutaneomuscular reflex
      was also investigated under the same paradigm following hemicerebellectomy. The
      enhancement of cutaneomuscular responses associated with subthreshold high
      frequency trains of stimulation following repetitive peripheral stimulation was
      prevented by hemicerebellectomy. Our results suggest that the pathways passing
      through the cerebellum are involved in the calibration of cutaneomuscular
      responses.

PMID- 16638608
TI  - Cerebrospinal fluid GABA levels in chronic migraine with and without depression.
AB  - Psychiatric comorbidity is one of the key elements in chronic migraine (CM)
      management. Depression is particularly common in these patients, occurring in up
      to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA)
      levels may be decreased in animal models of depression. Also, clinical studies
      have reported low level in mood disorder patients for both plasma and
      cerebrospinal fluid (CSF) GABA. We hypothesized that low GABA levels in the brain
      might be related to the depression associated with CM. We studied 14 chronic
      migraine patients, with or without depression, compared to age-and sex-matched
      controls. CSF GABA levels were measured by HPLC. CSF GABA levels showed
      significant lower levels in depressed patients than those without depression. No
      difference was found when comparing patients versus controls. A GABA deficiency
      may be the underlying mechanism of depression in CM. Hence, preventive therapies
      modulating GABA neurotransmission could be used in CM associated with depression.

PMID- 16638609
TI  - Neuronal apoptosis and gray matter heterotopia in microcephaly produced by
      cytosine arabinoside in mice.
AB  - Primary microcephaly can be accompanied by numerous migration anomalies. This
      experiment was undertaken to examine the pathogenesis of gray matter heterotopia
      and microcephaly that is produced after administering cytosine arabinoside (Ara
      C) to mice. Pregnant mice were intraperitoneally injected with Ara-C at 30 mg/kg
      body weight on days 13.5 and 14.5 of gestation, and then their offspring were
      examined. On embryonic day 15.5, in the ventricular zone of the cingulate cortex,
      the neuroepithelial cells lacked BrdU immunoreactivity. Nestin-immunoreactive
      radial glial fibers and calretinin-positive subplate fibers were disrupted. TUNEL
      reaction was remarkable throughout the cerebral hemisphere. Subcortical
      heterotopia in the cingulate cortex and subependymal nodular heterotopia in the
      dorsolateral part of the lateral ventricles became detectable by the first day
      after birth. Thirty-two days after birth, microcephaly was apparent; subcortical
      heterotopia was observed to have increased in size while it was still located in
      the frontal and cingulate cortices. This experiment demonstrated that Ara-C
      induces neuronal apoptosis throughout the cerebral hemisphere. The
      immunohistochemical characteristics in the gray matter heterotopia suggest that
      both the subcortical and the subependymal heterotopias were formed by neurons
      originally committed to the neocortex. We conclude that the gray matter
      heterotopia that accompanies the microcephaly was produced by a disturbance of
      radial, tangential, and interkinetic neuronal migrations due to the toxicity of
      Ara-C in the immature developing brain.

PMID- 16638610
TI  - The preconditioning modified neuronal expression of apoptosis-related proteins of
      Bcl-2 superfamily following severe hypobaric hypoxia in rats.
AB  - The patterns of expression of the Bcl-2, Bax, and Bcl-xL proteins were examined
      immunocytochemically in rat hippocampus and neocortex after severe hypobaric
      hypoxia (180 Torr for 3 h) and severe hypoxia preconditioned by intermittent mild
      hypoxia (360 Torr for 2 h daily, for 3 consecutive days, 24 h prior to severe
      hypoxia). As revealed by TUNEL assay, severe hypobaric hypoxia produced extensive
      apoptotic damage to the neurons of hippocampal CA1-CA4 and the neocortex but not
      the dentate gyrus granule cells. Remarkable posthypoxic up-regulation of Bax
      expression maximal at 24 h was detected in the CA1-CA4 areas of hippocampus and
      neocortex 3-72 h after severe hypoxia. The preconditioning to severe hypoxia
      protected neurons from the posthypoxic apoptotic transformations, the up
      regulation of Bax expression, and resulted in persistent overexpression of Bcl-2
      and Bcl-xL. We conclude that the protective action of hypoxic preconditioning is
      at least in part mediated by shifting of neuronal Bax/Bcl-2-Bcl-xL ratio to a
      favor of antiapoptotic proteins Bcl-2 and Bcl-xL.

PMID- 16638612
TI  - Retinal ganglion cell line apoptosis induced by hydrostatic pressure.
AB  - Cellular responses to changes in pressure are implicated in numerous disease
      processes. In glaucoma apoptosis of retinal ganglion cells (RGCs) is associated
      with elevated intra-ocular pressure, however, the exact cellular mechanisms
      remain unclear. We have previously shown that pressure can induce apoptosis in
      B35 and PC12 neuronal cell lines, using an in vitro model for pressure elevation.
      A novel RGC line allows us to study the effects of pressure on retinal neurons.
      'RGC-5' cultures were subjected to elevated ambient hydrostatic pressure
      conditions in our model. Experimental pressure conditions were 100 mm Hg and 30
      mm Hg, representing acute (high) and chronic (lower-pressure) glaucoma, and 15 mm
      Hg for normal intra-ocular pressure, set above atmospheric pressure for 2 h.
      Negative controls were treated identically except for the application of
      pressure, while positive controls were generated by treatment with a known
      apoptotic stimulus. Apoptosis was determined by a combination of cell morphology
      and specific TUNEL and Annexin V fluorescent markers. These were assessed
      simultaneously by laser scanning cytometry (LSC), which also enabled quantitative
      marker analysis. RGC-5 neurons showed a significantly increased proportion of
      apoptotic cells compared with controls; maximal at 100 mm Hg, moderate at 30 mm
      Hg and not statistically significant at 15 mm Hg. This graded response,
      proportionate to the level of pressure elevation, is representative of the
      severity of analogous clinical settings (acute, chronic glaucoma and normal).
      These results complement earlier findings of pressure-induced apoptosis in other
      neuronal cultures. They suggest the possibility of novel mechanisms of pressure
      related mechanotransduction and cell death, relevant to the pathogenesis of
      diseases such as glaucoma.

PMID- 16638611
TI  - Mitochondrial dysfunction and caspase activation in rat cortical neurons treated
      with cocaine or amphetamine.
AB  - Drug abuse is associated with brain dysfunction and neurodegeneration, and
      various recreational drugs induce apoptotic cell death. This study examined the
      role of the mitochondrial apoptotic pathway in psychostimulant-induced neuronal
      dysfunction. Using primary neuronal cultures, we observed that amphetamine
      (IC50=1.40 mM) was more potent than cocaine (IC50=4.30 mM) in inducing cell
      toxicity. Apoptotic cell death was further evaluated using cocaine and
      amphetamine concentrations that moderately decreased cell reduction capacity but
      did not affect plasma membrane integrity. Compared to cocaine, amphetamine highly
      decreased the mitochondrial membrane potential, as determined using the
      fluorescent probe rhodamine-123, whereas both drugs decreased mitochondrial
      cytochrome c. In contrast to amphetamine, cocaine cytotoxicity was partly
      mediated through effects on the electron transport chain, since cocaine toxicity
      was ameliorated in mitochondrial DNA-depleted cells lacking mitochondrially
      encoded electron transport chain subunits. Cocaine and amphetamine induced
      activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or 
      8. In addition, amphetamine, but not cocaine, was associated with the appearance
      of evident nuclear apoptotic morphology. These events were not accompanied by
      differences in the release of the apoptosis-inducing factor (AIF) from
      mitochondria. Our results demonstrate that although both amphetamine and cocaine
      activate the mitochondrial apoptotic pathway in cortical neurons, amphetamine is
      more likely to promote apoptosis.

PMID- 16638613
TI  - Challenging the philosophy of partnership with parents: a grounded theory study.
AB  - BACKGROUND: Parent participation is viewed as a pivotal concept to the provision
      of high quality nursing care for children and their families. Since the 1990's,
      the term 'partnership with parents' has increasingly been reported in the
      literature and adopted as a philosophy of care in most paediatric units in the
      United Kingdom. OBJECTIVES: To explore children's, parents', and nurses' views on
      participation in care in the healthcare setting. DESIGN: Using grounded theory,
      data were collected through in-depth interviews, and participant observation.
      Sample consisted of eleven children, ten parents and twelve nurses from four
      paediatric wards in two hospitals in England. RESULTS: Most nurses assumed that
      parents would participate in care and viewed their role as facilitators rather
      than 'doers'. Nurses reported that the ideology of partnership with parents did
      not accurately reflect or describe their relationships with parents. Parents
      could never be partners in care as control of the boundaries of care rested with
      the nurses. Parents felt compelled to be there and to be responsible for their
      children's welfare in hospital. CONCLUSIONS: The pendulum of parent participation
      has swung from excluding parents in the past to making parents feel total
      responsibility for their child in hospital. It is argued that the current models
      or theories on parent participation/partnership are inappropriate or inadequate
      because they do not address important elements of children's, parents' and
      nurses' experiences in hospital.

PMID- 16638614
TI  - The opinions of employed mothers about their own nutrition during lactation: a
      questionnaire survey.
AB  - OBJECTIVES: The main purpose of the study was to identify the changes employed
      mothers of infants aged 0-24 months made in their nutrition with the aim of
      increasing their milk production and extending their breastfeeding period.
      METHODS: The 135 full-time employed mothers enrolled in this study came to the
      Well-Child Clinic at Akdeniz University Hospital. Dietary data were collected
      from the mothers via a questionnaire prepared by the researchers to elicit
      details about what kind of foods or nutrition supplements women added, avoided or
      were recommended to avoid or add to their diets and why. RESULTS: All the mothers
      made changes in their diets while breastfeeding. The number one change that
      mothers made in their diet in order to increase milk production was to increase
      their fluid intake (38.6%) while the second was to increase their consumption of
      sweets (25.3%). The main type of food mothers were advised to avoid were dried
      legumes and grains (28.9%). The most important reason for this was the belief
      that they increased the chance of newborn colic (89.4%). There were statistically
      significant differences between foods avoided by breastfeeding mothers related to
      their age (chi(2)=6.88, p=.009), education level and those who mentioned
      increasing their consumption of fluid while breastfeeding (chi(2)=13.12, p=.000).
      CONCLUSIONS: All of the mothers espoused specific practices, and had been given
      recommendations by others about their nutrition while breastfeeding. Mothers need
      to be informed about the factors that increase and decrease milk production and
      affect infant colic, and should be encouraged that they can successfully
      breastfeed without increasing their consumption of sweets or avoiding dried
      legumes and some vegetables.

PMID- 16638615
TI  - The exocyclic amine at the RNase P cleavage site contributes to substrate binding
      and catalysis.
AB  - Most tRNAs carry a G at their 5' termini, i.e. at position +1. This position
      corresponds to the position immediately downstream of the site of cleavage in
      tRNA precursors. Here we studied RNase P RNA-mediated cleavage of substrates
      carrying substitutions/modifications at position +1 in the absence of the RNase P
      protein, C5, to investigate the role of G at the RNase P cleavage site. We
      present data suggesting that the exocyclic amine (2NH2) of G+1 contributes to
      cleavage site recognition, ground state binding and catalysis by affecting the
      rate of cleavage. This is in contrast to O6, N7 and 2'OH that are suggested to
      affect ground state binding and rate of cleavage to significantly lesser extent.
      We also provide evidence that the effects caused by the absence of 2NH2 at
      position +1 influenced the charge distribution and conceivably Mg2+ binding at
      the RNase P cleavage site. These findings are consistent with models where the
      2NH2 at the cleavage site (when present) interacts with RNase P RNA and/or
      influences the positioning of Mg2+ in the vicinity of the cleavage site.
      Moreover, our data suggest that the presence of the base at +1 is not essential
      for cleavage but its presence suppresses miscleavage and dramatically increases
      the rate of cleavage. Together our findings provide reasons why most tRNAs carry
      a guanosine at their 5' end.

PMID- 16638616
TI  - Involvement of Sp-1 in the regulation of the Id-1 gene during trophoblast cell
      differentiation.
AB  - Id-1, a member of the helix-loop-helix transcription factor family, inhibits the
      differentiation of Rcho-1 cells, which were derived from rat choriocarcinoma and
      consist of trophoblast stem cells. Id-1 is expressed at a high level in
      undifferentiated trophoblast stem cells and then down-regulated during early
      differentiation, and is thought to be a key regulator in the trophoblast giant
      cell differentiation pathway. In this study, we analyzed the signaling mechanism
      regulating the high expression levels of Id-1 in undifferentiated Rcho-1 cells.
      Promoter deletion analysis revealed that a 31-bp sequence (Box-2 region), located
      between -200 and -169bp in the Id-1 promoter is necessary for the promoter
      activity. Electrophoretic mobility shift assays and DNA affinity precipitation
      assays showed that Box-2-binding activity was decreased during differentiation
      and that Sp-1 protein bound to this sequence. The protein level of Sp-1 was
      decreased during the differentiation. These results suggest that the Sp-1 protein
      level may regulate the Box-2-binding activity and the trophoblast giant-cell
      differentiation.

PMID- 16638617
TI  - Evaluation of the estrogenic potential of river and treated waters in the Paris
      area (France) using in vivo and in vitro assays.
AB  - For many years, surface waters have been shown to be contaminated by endocrine
      disrupting compounds (EDCs), which can cause adverse effects on human and
      wildlife growth, development, and reproduction. It is therefore of primary
      importance to determine if drinking water could be contaminated by EDCs when
      produced from polluted surface waters. It is also essential to determine if
      disinfection by-products can account for estrogenic activity in treated waters.
      The estrogenic potential of river and treated waters was investigated using an in
      vivo assay. Adult male zebrafish were placed in three drinking water treatment
      plants (DWTPs) in the Paris area and exposed for 1 month to the two types of
      waters. After exposure, vitellogenin (VTG) was measured in the plasma of fish
      using a competitive ELISA. In addition, an in vitro assay (MELN cells) was used
      to assess the estrogenic potential of 10 major chlorination by-products. No
      significant induction of VTG was observed in fish exposed to river or treated
      waters. Among the 10 chlorination by-products tested, only 2-chlorophenol was
      found to be weakly estrogenic at concentrations up to 1mg/L. Therefore, the risk
      for the three DWTPs studied to produce drinking water with significant level of
      estrogenic substances appears to be low.

PMID- 16638618
TI  - Kinetic characterization of the inhibition of acyl coenzyme A: steroid
      acyltransferases by tributyltin in the eastern mud snail (Ilyanassa obsoleta).
AB  - Exposure to tributyltin (TBT) has been causally associated with the global
      occurrence of a pseudohermaphroditic condition called imposex in neogastropod
      species. TBT elevates free testosterone levels in these organisms, and this
      upsurge in testosterone may be involved in the development of imposex. We
      investigated the ability of TBT to inhibit acyl coenzyme A:testosterone
      acyltransferase (ATAT) activity as well as microsomal acyl-coenzyme A:17beta
      estradiol acyltransferase (AEAT) in a neogastropod, the eastern mud snail
      Ilyanassa obsoleta as a mechanism by which TBT elevates free testosterone. TBT
      significantly inhibited both ATAT and AEAT activities in vitro at toxicologically
      relevant in vivo concentrations. Kinetic analyses revealed that TBT is a
      competitive inhibitor of ATAT (K(i)= approximately 9microM) and is a weaker,
      noncompetitive inhibitor of AEAT (K(i)= approximately 31microM). ATAT and AEAT
      activities associated with different microsome preparations were significantly
      correlated, and 17beta-estradiol competitively inhibited the fatty acid
      esterification of testosterone suggesting that one enzyme is responsible for
      biotransforming both testosterone and 17beta-estradiol to their corresponding
      fatty acid esters. Overall, the results of this study supply the much-needed
      mechanistic support for the hypothesis that TBT elevates free testosterone in
      neogastropods by inhibiting their major regulatory process for maintaining free
      testosterone homeostasis-the fatty acid esterification of testosterone.

PMID- 16638619
TI  - An overview of the BEEP Stavanger workshop.
AB  - Within the three-year European Research Project BEEP (Biological Effects of
      Environmental Pollution in marine ecosystems), a workshop was carried out at the
      facility of Akvamiljo a.s. with the scientific support of IRIS (International
      Research Institute of Stavanger) researchers. Validation of newly developed
      biomarkers, especially at the molecular level, was the core part of the activity.
      Two large scale mesocosm exposures were done and samples shared between the
      participants (about 30 Institute), allowing an integrated approach for studying
      the effects of several pollutants selected as environmentally important issues
      (i.e. PAHs, alkyl phenols, bisphenol A, diallyl phthalate and polybrominated
      diphenyl ether). In addition, a field study (Visne, Norway) has been performed
      for the validations of biomarkers under environmental conditions. The Stavanger
      workshop demonstrates the importance of collaboration between researchers to
      establish common ways to proceed in biomarker analysis. The common exposures
      encourage a joint strategy for planning biomonitoring activity. A clarification
      in this direction is needed to coordinate results from numerous studies about the
      environmental impact of pollutants which are currently carried out all over
      Europe and around the world. Expertise in various disciplines is required to plan
      and perform a successful monitoring activity and to study/predict the effect of
      environmental pollutants. Biologists, chemists, statisticians and environmental
      researchers should always be included. The Stavanger workshop also indicated the
      importance of developing multivariate statistical methods to enable
      interpretation of complex data sets. It is of interest to develop statistical
      tools which can integrate the results from a battery of biomarkers in order to
      obtain a more complete picture of environmental impact.

PMID- 16638620
TI  - Intelligent classification of electrocardiogram (ECG) signal using extended
      Kalman Filter (EKF) based neuro fuzzy system.
AB  - This study presents the development of a hybrid system consisting of an ensemble
      of Extended Kalman Filter (EKF) based Multi Layer Perceptron Network (MLPN) and a
      one-pass learning Fuzzy Inference System using Look-up Table Scheme for the
      recognition of electrocardiogram (ECG) signals. This system can distinguish
      various types of abnormal ECG signals such as Ventricular Premature Cycle (VPC),
      T wave inversion (TINV), ST segment depression (STDP), and Supraventricular
      Tachycardia (SVT) from normal sinus rhythm (NSR) ECG signal.

PMID- 16638621
TI  - A phase I/II trial of weekly docetaxel and gefitinib in elderly patients with
      stage IIIB/IV non-small cell lung cancer.
AB  - BACKGROUND: Phase III trials in elderly patients with advanced (stage IIIB/IV)
      non-small cell lung cancer (NSCLC) reveal treatment with single agent
      chemotherapy improves survival. The role of double agent therapy in this patient
      population is an area of investigation. METHODS: A phase I/II trial was performed
      in elderly patients (age>or=70 years) with stage IIIB/IV disease and Eastern
      Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were
      treated with gefitinib 250 mg daily. Patients received docetaxel on a treatment
      schedule of days 1, 8, 15 of an every 28 days schedule. The phase I portion of
      the trial consisted of dose escalation docetaxel from 30 to 36 mg/m2 using a
      three patient cohort design. The trial design contained continuous monitoring for
      excessive toxicity with pre-selected toxicity boundaries. RESULTS: Twenty-six
      patients were evaluable for efficacy and toxicity analysis. The median age was
      75.5 years. The majority of the patients had stage IV disease (85%), ECOG
      functional status of 0-1 (81%), were male (65%), and current or former smokers
      (88%). Eleven patients experienced National Cancer Institute Common Toxicity
      Criteria grades 3-5 non-hematologic toxicity during the first cycle. The toxicity
      was determined to be unexpected, and the trial was discontinued. Overall response
      rate (complete+partial responses) was 31%, and the median survival was 6.5 months
      (95% confidence interval (CI) (3.6-9.0)), and estimated 1-year survival rate was
      27% (95% CI (13-55%)). CONCLUSIONS: The combination of weekly docetaxel and
      gefitinib had activity; however, unexpected toxicity was observed in the elderly
      patient population.

PMID- 16638622
TI  - Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive
      impairment.
AB  - We compared plasma levels of beta-amyloid 1-42 (pg/ml) found for 146 sporadic
      Alzheimer (AD) patients, 89 subjects with mild cognitive impairment (MCI) and 89
      age-matched controls (CT). AD patients had significantly lower levels (38, 54,
      52; p<0.01), unrelated to severity of the disease as assessed by MMSE score, age,
      sex or APOE4 status. Twenty cases investigated at two time points 18 months apart
      did not demonstrate further decreases. Thus, the reduction in beta-amyloid 1-42
      may be a marker for AD status, specifically, a transition from normal status or
      MCI to AD, rather than a marker for neurodegenerative processes occurring in the
      disease.

PMID- 16638623
TI  - Control and adherence: living with diabetes in Bangkok, Thailand.
AB  - Diabetes is managed via a regimen of control. Physicians advise adults living
      with type 2 diabetes to control blood sugar levels by controlling diet,
      maintaining regular exercise, and complying with medication. The extent to which
      individuals are able to adhere to such recommendations varies. In this article,
      we explore lay perceptions of diabetes and its control, drawing on data from an
      ethnographic study conducted in Bangkok, Thailand. Between August 2001 and
      February 2003 the first author spent time with twelve man and women living with
      type 2 diabetes, their spouses, children and health providers. An additional 21
      people were interviewed to extend the data and test for generalisibility. It was
      found that individual explanations of control, and adherence or resistance to
      medical advice, are interpreted and adapted in ways consistent with Buddhist
      philosophy and Thai norms that govern everyday life. Notions of moderation and
      cultural values of being and behaving, and ideals of interaction, provide a
      philosophical basis and practical guidelines for control.

PMID- 16638624
TI  - Aberrant accumulation of serotonin in dopaminergic neurons.
AB  - Gene targeting approaches greatly facilitate insight into the functioning of
      monoamine transporters, the targets of potent antidepressants. The serotonin
      transporter (5-HTT) is the molecular target of a large number of antidepressants.
      To assess the clearance of serotonin (5-HT) in the absence of the 5-HTT, we have
      generated double knockout mice lacking both the 5-HTT and the catabolizing enzyme
      monoamine oxidase A (MAOA). We found aberrant 5-HT accumulation in the striatum
      of these MAOA/5-HTT double knockout mice. By additional ablation of the dopamine
      transporter (DAT), this aberrant 5-HT accumulation was abolished in MAOA/5
      HTT/DAT triple knockout mice. Thus, aberrant uptake of 5-HT occurs in
      dopaminergic terminals under conditions of elevated 5-HT levels, and this
      aberrant uptake is mediated by the DAT. These findings have important
      consequences for antidepressant therapy, since during treatment of depression
      with selective serotonin reuptake inhibitors, clearance of 5-HT by dopaminergic
      neurons may reduce the desired therapeutic elevation of extracellular 5-HT
      levels. This provides a molecular rationale for improving antidepressant efficacy
      by additional pharmacological inhibition of the DAT.

PMID- 16638625
TI  - Naegleria fowleri-associated encephalitis in a cow from Costa Rica.
AB  - Species of Naegleria, Acanthamoeba, and Balamuthia are soil amoebae that can
      cause encephalitis in animals and humans. Of these, Naegleria fowleri is the
      cause of often fatal primary meningoencephalitis in humans. N. fowleri-associated
      encephalitis was diagnosed in a cow that was suspected to have rabies. Only
      formalin-fixed brain was available for diagnosis. There was severe
      meningoencephalitis involving all parts of the brain and numerous amoebic
      trophozoites were present in lesions. The amoebae reacted with N. fowleri
      specific polyclonal antibodies in an indirect immunofluorescent antibody test.
      This is the first report of amoebic encephalitis in any host from Costa Rica.

PMID- 16638626
TI  - Quantitation of alpha-fetoprotein messenger RNA for early detection of recurrent
      hepatocellular carcinoma: a prospective pilot study.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) may be a potential
      marker of the dissemination of hepatocellular carcinoma (HCC) cells into the
      circulation. The aim of this prospective pilot study was to assess the prognostic
      value of quantitative levels of AFP mRNA in patients undergoing ablative
      treatment for HCC. METHODS: Peripheral blood samples were taken from seven
      patients before and after treatment for measurement of AFP mRNA levels by reverse
      transcriptase polymerase chain reaction (RT-PCR). Patients were treated with
      percutaneous radiofrequency thermal ablation (n=3) or transarterial
      chemoembolization (n=4). The level of AFP mRNA in blood was serially determined,
      and the time course was related to the clinical course and disease outcome. The
      median duration of follow-up was 14 months (range, 9-16 months). RESULTS: HCC
      recurred locally in four patients, and lung metastases developed in two of them.
      Patients were divided into three groups on the basis of the pre- and post
      treatment AFP mRNA status. Group 1 included four patients with consistently high
      serum AFP and AFP mRNA levels (pre- and post-treatment). These patients developed
      distant and local recurrence. Group 2 included a patient with serum-negative AFP
      mRNA and normal AFP levels at entry. Although serum AFP remained within normal
      range, mean AFP mRNA increased from 10 to 95 copies/microg RNA. This patient had
      no distant metastases, but his tumor markedly increased in size. In Group 3, AFP
      mRNA and serum AFP remained within normal range before and after treatment. These
      two patients did not develop either local or distant metastases during the follow
      up period. CONCLUSIONS: Although this is a small sample size pilot study these
      findings imply that quantitative measurement of AFP-expressing cells in
      peripheral blood may serve as a marker of HCC recurrence.

PMID- 16638627
TI  - Distribution of glutathione S-transferase M1, P1 and T1 genotypes in different
      age-groups of Finns without diagnosed cancer.
AB  - BACKGROUND: Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of
      hazardous environmental agents, and their polymorphisms may therefore modify the
      risk of environmentally induced cancers. Consequently, the XME polymorphisms have
      been extensively studied in this context during recent years. Particular
      attention has been given to the polymorphisms of glutathione S-transferase (GST)
      M1, P1 and T1 genes. Previous studies have provided abundant data indicating
      these polymorphisms as important modifiers of individual susceptibility to
      cancers of environmental origin. It can be postulated that if the at-risk
      genotypes of these genes were real risk factors for the environmental cancers,
      their prevalence would presumably decrease with age in cancer-free part of the
      population. METHODS: We tested the hypothesis in a population based group of 2105
      Finns (1,051 men, 1,054 women) in five age strata (27, 37, 47, 57 and 67 years of
      age), all without clinically diagnosed cancer. RESULTS: For GSTM1 genotype, a
      significant interaction was seen between gender and age among never smokers
      (p=0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31
      1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97-2.97)
      homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the
      likelihood of being a concurrent carrier of the putatively protective genotypes
      of all of the three studied GSTs was almost three-fold (OR 2.80, 95% CI 1.10
      7.12) in heavy smokers in the two oldest age-groups compared with the other
      genotypes. CONCLUSIONS: Our findings based on a novel study design provide
      support to the previous case-control studies suggesting that GST genotypes modify
      individual risk of environmentally-induced cancers.

PMID- 16638628
TI  - Colorectal cancer prevention: adherence patterns and correlates of tests done for
      screening purposes within United States populations.
AB  - BACKGROUND: Studies exploring CRC testing prevalence and correlates within US
      populations have provided limited and sometimes conflicting information. The most
      recent national-level reports have described US usage of CRC tests but none have
      considered only those tests done specifically for screening reasons as an outcome
      variable. METHODS: Using the NHIS 2000 sample of >or=50 year-old, we assessed
      screening behavior using an outcome variable accounting for (1) any combination
      of recommended tests (2) done within their respective time guidelines, and (3)
      specifically for screening purposes. RESULTS: Only 25.8% (95% CI: 24.9-26.7%) of
      the population reported getting a test done for screening purposes within the
      recommended time. Most (>85%) of the FOBTs and only about 60% of endoscopies were
      done for screening. Among those who had an endoscopy within the recommended time,
      Blacks were more likely than Whites to report screening as the purpose of the
      test. Hispanics had the lowest test usage irrespective of test time, reason or
      type. Hispanics were 50% (p<0.001) less likely to be adherent, and Blacks
      approximately 22% (p<0.01) less likely to be adherent, than Whites. After
      multivariate adjustment, differences between Whites and Blacks disappeared;
      Hispanics remained less likely. Increasing education predicted higher adherence
      among Whites but only undergraduate completion did so among Blacks. Male gender
      predicted adherence only among Blacks and insurance only among Hispanics.
      CONCLUSIONS: Preventive screening for CRC is lower than estimates from previous
      studies. Future studies should consider accounting for test purpose. Our findings
      need confirmation through studies based on objective data.

PMID- 16638629
TI  - Polymorphism of the PE domain of PE/PE_PGRS sequences in clinical isolates of
      Mycobacterium bovis in Mexico.
AB  - Polymorphism of the PE domain of PE/PE_PGRS sequences was studied in
      Mycobacterium bovis isolates from different Mexican states. Samples were analyzed
      by spolygotyping and RFLP using IS6110 and a 235-bp fragment of the PE domain of
      PE/PE_PGRS as probes. With the PE probe, three different genotypes were observed,
      one being predominant in all states. These results confirm the high conservation
      of the PE domain and suggests a potential role for PE sequence as a stable
      genetic marker for bovine tuberculosis.

PMID- 16638630
TI  - Further exploration of the Penh parameter.
AB  - Unrestrained plethysmography (UP) has been widely used to measure airway
      reactivity in conscious mice. It is non-invasive, easy to use, suitable for
      longitudinal studies, and allows a large throughput of animals for screening
      purposes. A non-dimensional parameter based on a characteristic change in the
      expiratory waveshape of the UP box signal, Penh, has been used as an indicator of
      bronchconstriction. Hamelmann et al. [Non-invasive measurement of airway
      responsiveness in allergen mice using barometric plethysmography. Am J Respir
      Crit Care Med 1997;156:766-77] presented experimental data showing a correlation
      between Penh and intrapleural pressure, as well as lung resistance; and Dohi et
      al. [Non-invasive system for evaluating the allergen-specific airway response in
      a murine model of asthma. Lab Invest 1999;79:1559-71] showed that Penh tracked
      the bronchial response to allergen challenge. More recently, papers and letters
      to the editor have argued against the use of UP and Penh in resistance
      applications, presenting mathematical and theoretical arguments that the UP
      waveform, and parameters derived from it (Penh) are dominated by conditioning,
      and are essentially unrelated to resistance [Lundblad et al. A reevaluation of
      the validity of UP in mice. J Appl Physiol 2002;93:1198-207; Mitzner and
      Tankersley. Interpreting Penh in mice. J Appl Physiol 2003;94:828-32]. This paper
      discusses the mathematics of UP as applied to two types of whole body
      plethysmographs (WBPs): a sealed chamber (pressure plethysmograph, PWBP); and a
      chamber with a pneumotachograph in its wall (flow plethysmograph, FWBP). We show
      that the PWBP waveform is largely dominated by conditioning, and exhibits little
      effect due to resistance; thus supporting the claim that UP and Penh are
      unrelated to resistance, when applied to measurements at typical room
      temperatures. By contrast, the effects of resistance or specific airway
      resistance (sRaw) are evident in the FWBP waveform, even at room temperature.
      Penh is derived from the FWBP waveform. We show that the changes in the FWBP
      waveform which occur in response to methacholine challenge cannot be due to
      conditioning, and are not simply due to changes in respiratory timing. Finally,
      we describe how Penh quantifies those changes.

PMID- 16638631
TI  - Production of an extracellular alkaline metalloprotease from a newly isolated,
      moderately halophile, Salinivibrio sp. strain AF-2004.
AB  - An extracellular protease was produced under stress conditions of high
      temperature and high salinity by a newly isolated moderate halophile,
      Salinivibrio sp. strain AF-2004 in a basal medium containing peptone, beef
      extract, glucose and NaCl. A modification of Kunitz method was used for protease
      assay. The isolate was capable of producing protease in the presence of sodium
      chloride, sodium sulfate, sodium nitrate, sodium nitrite, potassium chloride,
      sodium acetate and sodium citrate. The maximum protease was secreted in the
      presence of 7.5 to 10% (w/v) sodium sulfate or 3% (w/v) sodium acetate (4.6 U ml(
      1)). Various carbon sources including glucose, lactose, casein and peptone were
      capable of inducing enzyme production. The optimum pH, temperature and aeration
      for enzyme production were 9.0, 32 degrees C and 220 rpm, respectively. The
      enzyme production corresponded with growth and reached a maximum level during the
      mid-stationary phase. Maximum protease activity was exhibited in the medium
      containing 1% (w/v) NaCl at 60 degrees C, with 18% and 41% activity reductions at
      temperature 50 and 70 degrees C, respectively. The optimum pH for enzyme activity
      was 8.5, with 86% and 75% residual activities at pH 10 and 6, respectively. The
      activity of enzyme was inhibited by EDTA. These results suggest that the protease
      secreted by Salinivibrio sp. strain AF-2004 is industrially important from the
      perspectives of its activity at a broad pH ranges (5.0-10.0), its moderate
      thermoactivity in addition to its high tolerance to a wide range of salt
      concentration (0-10% NaCl).

PMID- 16638632
TI  - Analysis of degradation of bacterial cell division protein FtsZ by the ATP
      dependent zinc-metalloprotease FtsH in vitro.
AB  - The identity of protease(s), which would degrade bacterial cell division protein
      FtsZ in vivo, remains unknown. However, we had earlier demonstrated that
      Escherichia coli metalloprotease FtsH degrades E. coli cell division protein FtsZ
      in an ATP- and Zn(2+)-dependent manner in vitro. In this study, we examined FtsH
      protease-mediated degradation of FtsZ in vitro in detail using seven different
      deletion mutants of FtsZ as the substrates, which lack different extents of
      specific regions at the N- or C-terminus. FtsH protease assay in vitro on these
      mutants revealed that FtsH could degrade all the seven deletion mutants
      irrespective of the deletions or the extent of deletions at the N- or C-terminus.
      These observations indicated that neither the N-terminus nor the C-terminus was
      required for the degradation of FtsZ, like already known in the case of the FtsH
      substrate sigma(32) protein. The recombinant clones expressing full-length FtsZ
      protein and FtsZ deletion mutant proteins would be useful in investigating the
      possibility of FtsZ as a potential in vivo substrate for FtsH in ftsH-null cells
      carrying ftsH suppressor function and ectopically expressed FtsH protease.

PMID- 16638633
TI  - Protective effect of silymarin on oxidative stress in rat brain.
AB  - Brain is susceptible to oxidative stress and it is associated with age-related
      brain dysfunction. Previously, we have pointed out a dramatic decrease of
      glutathione levels in the rat brain after acetaminophen (APAP) oral
      administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans
      isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of
      alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study,
      we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant
      defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats
      were treated with SM (200 mg/kg/die orally) for three days, or with APAP single
      oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and
      APAP single oral administration (3 g/kg) at third day. Successively the following
      parameters were measured: reduced and oxidized glutathione (GSH and GSSG),
      ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD)
      and malondialdehyde levels (MDA). Our results showed a significant decrease of
      GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels
      after APAP administration. After SM administration GSH and AA significantly
      increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH
      values significantly increase and the others parameters remained unchanged
      respect to control values. These results suggest that SM may to protect the SNC
      by oxidative damage for its ability to prevent lipid peroxidation and
      replenishing the GSH levels.

PMID- 16638634
TI  - Time trends in smoking habits among Italian young adults.
AB  - BACKGROUND: In most developed countries the prevalence of smoking habits is
      decreasing in men, while in women the prevalence seems to decline in Northern
      Europe but to increase in the Mediterranean area. The present research aims at
      assessing time trends in smoking habits in Italy. METHODS: In the frame of the
      Italian Study on Asthma in Young Adults (ISAYA) a random sample of the Italian
      population aged 20-45 years was administered a mailed questionnaire in 9 Italian
      centers between 1998 and 2000. Cumulative response was 72.7% (18873/25969).
      Kaplan-Meier survival curves and log-rank test were used to compare probability
      of remaining a life-time non-smoker across birth cohorts (1953-58, 1959-63, 1964
      68, 1969-73, 1974-78). Probability to quit smoking was also evaluated among ever
      smokers. RESULTS: Probability to persist as a non-smoker significantly increased
      across subsequent generations in both sexes. At the age of 20 years this
      probability amounted to 41.7% (95% CI 39.4-44.0%) in men and 52.7% (50.4-54.9%)
      in women born between 1953 and 1958, and it increased to 57% (54.8-59.1%) in men
      and 68.7% (66.6-70.7%) in women born in 1969-73, but no further decline in
      smoking habits was observed in the next birth cohort (1974-78). Also the
      probability to quit smoking significantly increased from the 1953-58 birth cohort
      to the 1969-73 one. CONCLUSIONS: Smoking has declined among Italian young adults
      of both genders. Further efforts are necessary to promote active anti-smoking
      campaign, especially among adolescents, which are at higher risk of starting to
      smoke.

PMID- 16638635
TI  - Mycobacterial infection of intraparenchymal bronchogenic cysts.
AB  - Bronchogenic cysts (BCs) may rarely cause some interesting and unusual
      complications. Although infection is a common complication of BCs, there are only
      two patients with BC infected with mycobacterium in English literature. Two
      intraparenchymal BCs infected with mycobacterium are presented here as unusual
      complications. Cystectomy was performed for the cysts. They were given
      antituberculosis treatment. No complication or recurrences were detected in
      follow up period.

PMID- 16638636
TI  - Carbon nanotube based aliphatic hydrocarbon sensor.
AB  - A hybrid multi-walled carbon nanotube (MWCNT) based chemical sensor was designed
      and developed by integration of microfabrication techniques with nano-assembly.
      This integrated sensing mechanism on a chip, comprised of thiol functionalized
      MWCNTs that functioned as transducers which were integrated with micro-electrode
      array measurement sites. The detection of the four fundamental hydrocarbons
      belonging to the aliphatic hydrocarbon family--methanol, ethanol, propanol and
      butanol was experimentally demonstrated. High degree of selectivity was
      demonstrated by repeated robust identification of individual hydro carbons
      belonging to the same family. The sensor demonstrated 1 ppm detection
      sensitivity. The detection mechanism was based on nano-scale transduction of the
      detection of the localized binding event between the functional binding sites and
      the chemical species of interest. Specific electrical signatures for each of
      these chemicals were identified using multiple levels of data analysis comprising
      of Fast Fourier Transformation (FFT) and Power Spectral Density (PSD). The sensor
      demonstrated a rapid response time with portability, accuracy and versatility for
      the in situ detection of multiple chemical agents, with potential for automation.

PMID- 16638637
TI  - The venom gland of queens of Apis mellifera (Hymenoptera, Apidae): morphology and
      secretory cycle.
AB  - The venom gland of queens of Apis mellifera was examined through light and
      transmission electron microscopy and subjected to electrophoretic analyses.
      Virgin queens exhibited prismatic secretory cells containing large amounts of
      rough endoplasmic reticulum with dilated cisternae, open secretory spaces,
      numerous vacuoles and granules scattered in the cytoplasm, and spherical nuclei
      with numerous nucleoli. The secretion produced was non-refringent under polarized
      light and the electrophoretic analysis of glandular extracts revealed five main
      protein bands. In mated queens, the venom gland exhibited a high degree of
      degeneration. Its secretion was refringent under polarized light and one of the
      main bands was absent in the electrophoretic pattern obtained. The morphological
      aspects observed are in agreement with the function of this gland in queens,
      given that virgin queens use venom in battles for the dominance of the colony, a
      situation that occurs as soon as they emerge, while fertilized queens rarely use
      venom.

PMID- 16638638
TI  - Skeletal changes after experimentally displaced condylar process fracture in
      growing rats.
AB  - INTRODUCTION: Fractures of the mandibular condyle are common. A potential for
      growth disturbances in young individuals has been reported; however, there are
      few experiments studying such consequences. Skeletal changes after fracture of
      the condyle in the growing period were analysed in this study. MATERIAL: Fifty
      young Wistar rats weighing 100g were used. Under general anaesthesia unilateral
      fracture dislocations of the condylar process were induced surgically in the
      experimental group (n=25), while only surgical access was performed in the sham
      operated group. The animals were sacrificed at 3 months of age. The mandibles
      were disarticulated, and radiographs were taken (axial skulls and lateral
      hemimandibles). Cephalometric evaluations were made using a computer system.
      Statistical tests were applied between groups and contralateral sides in each
      group. RESULTS: There were atrophy and degenerative change of the fractured
      condylar process. There was also a significant difference in the height of the
      mandibular body and in the length of anterior and posterior maxilla. CONCLUSION:
      It was concluded that an experimental fracture of the mandibular condyle during
      the growing period in rats induced degenerative changes of the condyle as well as
      an asymmetry of the mandible, affecting height of the body, also leading to
      consequences in the maxilla.

PMID- 16638639
TI  - The discovery of the selective I(f) current inhibitor ivabradine. A new
      therapeutic approach to ischemic heart disease.
AB  - Coronary artery disease is still a major cause of morbidity and mortality in the
      industrialized countries, despite the advances in pharmacological treatments,
      risk factor control and the beneficial effect of myocardial revascularization
      procedures. Medical anti-ischemic treatment is still essential in most patients,
      but should be improved in terms of efficacy and tolerance to ensure better
      prevention of mortality and improvement of the quality of life and symptom
      control. Since increased heart rate plays a major role in coronary artery
      disease, not only as a trigger of most of the ischemic episodes but also as an
      independent predictor of mortality, inhibition of the pacemaker I(f) current to
      induce a direct and selective decrease in heart rate represents an attractive
      therapeutic approach for coronary artery disease. The screening of original
      benzocycloalkane compounds, at Servier Research Institute, has led to the
      selection of ivabradine for clinical development. Preclinical data showed that
      ivabradine inhibits the I(f) current of the sinus node, induces a selective
      reduction in heart rate, both at rest and during exercise, preserves myocardial
      contractility, atrio-ventricular conduction and ventricular repolarization.
      Ivabradine prevents exercise-induced myocardial ischemia as effectively as a beta
      blocker while offering better protection of regional myocardial contractility.
      These data have been confirmed in humans, and in particular, the anti-ischemic
      efficacy of ivabradine, at least as effective as a beta-blocker, in patients with
      stable angina. Large ongoing clinical trials aim to assess the therapeutic value
      of ivabradine to improve the prognosis of patients with stable coronary disease
      and left ventricular systolic dysfunction by reducing mortality and the
      occurrence of major cardiovascular events.

PMID- 16638640
TI  - Funny channels in the control of cardiac rhythm and mode of action of selective
      blockers.
AB  - "Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally
      described as an inward current activated on hyperpolarization to the diastolic
      range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble,
      SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The
      involvement of funny channels in the generation and modulation of cardiac
      pacemaker activity has been amply demonstrated by thorough analysis since its
      discovery. The degree of funny current activation upon termination of an action
      potential determines the slope of diastolic depolarization, and hence pacemaker
      frequency; furthermore, I(f) is under cAMP-mediated control by beta-adrenergic
      and muscarinic stimulation and underlies the modulation of cardiac rate by the
      autonomous nervous system: it therefore represents a mechanism of fundamental
      physiological relevance. Their function in pacemaking makes funny channels an
      obvious target for drugs aiming at regulation of spontaneous activity and cardiac
      rate. This explains the recent development of "heart rate-reducing" drugs which
      act as selective f-channel inhibitors, and as such are capable of specifically
      slow cardiac frequency by decreasing the rate of diastolic depolarization. These
      substances will be useful in treating diseases such as chronic angina and heart
      failure. Furthermore, in situ delivery of funny channels, or of a cellular source
      of funny channels, is a promising new technique for the development of biological
      pacemakers which may in a near future replace electronic devices. Finally, a
      channel mutation responsible for one type of a relatively common rhythm
      disturbance, sinus bradycardia, has been recently identified, highlighting the
      clinical relevance of funny channels in the pacemaker function.

PMID- 16638641
TI  - Thrombin-induced caspases 3 and 9 translocation to the cytoskeleton is
      independent of changes in cytosolic calcium in human platelets.
AB  - Apoptosis has been shown to be associated with changes in cytosolic free calcium
      concentration ([Ca(2+)](c)). Here we show that the agonist thrombin induces
      activation of caspases 9 and 3 and translocation of the caspase active forms and
      procaspases to the cytoskeleton in human platelets. Dimethyl-BAPTA loading did
      not affect thrombin-induced caspase 9 and 3 activation or translocation
      suggesting that these responses are independent of increases in [Ca(2+)](c).
      Treatment with thapsigargin plus ionomycin, to induce extensive Ca(2+) store
      depletion and subsequent increase in [Ca(2+)](c), stimulates caspase activation
      although it was unable to induce caspase translocation to the cytoskeleton.
      Similar results were observed in cells loaded with dimethyl-BAPTA, suggesting
      that activation of caspases 9 and 3 by thapsigargin plus ionomycin does not
      require rises in [Ca(2+)](c). These findings suggest that thrombin-induced
      caspase 9 and 3 activation and translocation are independent on rises in
      [Ca(2+)](c) but might require store depletion in human platelets.

PMID- 16638642
TI  - A population based study of epilepsy in children from a Swedish county.
AB  - BACKGROUND: Epidemiological studies of childhood epilepsy are of importance to
      compare incidence and prevalence rates, age distribution, inheritance, seizure
      types, epilepsy syndromes and treatment strategies. AIM: To perform an
      epidemiological study on children with epilepsy in a Swedish county using current
      ILAE classifications and a recent proposal. METHODS: A population-based study was
      performed using the hospital data register to select children aged 1 month to 16
      years with the diagnosis 'convulsions' or 'epilepsy' recognized between January
      1996 and December 2000. Only patients with active epilepsy were included.
      RESULTS: Two hundred and five children met the study criteria on the prevalence
      day 31st December, 2000. The total prevalence rate was 3.4/1,000 with a peak
      prevalence in the age group 8-11 years. The incidence year 2000 was 40/100,000.
      Additional neuroimpairments were registered in 47.3%. A majority of the patients,
      54.0%, had focal or focal plus secondarily generalized seizures. A named syndrome
      could be diagnosed in 49.4%. The most common syndrome was rolandic epilepsy
      occurring in 17.0%. Childhood absence epilepsy occurred in 5.9%. Different
      disorders associated with epilepsy were found in 31.7%. The most common
      associated phenomenon was malformation of cortical development. Antiepileptic
      drug treatment was used in 81.0%, the most common first choice being valproate.
      CONCLUSIONS: The prevalence and incidence rates in this strictly delineated study
      are lower than those found in other epidemiological studies. Together with many
      divergences between reported studies concerning frequencies of different items,
      the results apparently depend on design, e.g. differences in age groups included,
      inclusion criteria used, and general methodology.

PMID- 16638643
TI  - Local genotoxic effects of formaldehyde in humans measured by the micronucleus
      test with exfoliated epithelial cells.
AB  - Formaldehyde (FA) is genotoxic in vitro in cultured mammalian cells. When FA
      reaches the nuclear DNA, it forms DNA-protein cross-links (DPX). Incomplete
      repair of DPX can lead to the formation of mutations, in particular chromosome
      mutations and micronuclei (MN) in proliferating cells. Due to its high
      reactivity, FA leads primarily to local genotoxic effects at the site of contact.
      In humans, local genotoxic effects of FA have been studied with the micronucleus
      test (MNT) in exfoliated nasal and buccal mucosa cells. This approach is
      considered to be highly relevant because these tissues are the actual targets of
      FA, and MN are a sensitive indicator for the mutagenic action of FA. The
      published studies suggest that inhalation of FA leads to increased MN frequencies
      in nasal and/or buccal mucosa cells. However, a critical review of the data
      reveals that the effects are not consistent, and the studies should be
      interpreted with caution. One problem is the lack of standardization of the MNT
      with exfoliated cells and the high assay variability. Another problem concerns
      the quality of published studies indicating local genotoxic effects of FA in
      humans. Incomplete information on study design, exposure, and confounding factors
      frequently limit the interpretation of these studies. On the basis of the
      available data, it is not yet possible to assess the local genotoxicity of FA in
      humans and to draw meaningful conclusions with regard to a dose-effect
      relationship for risk estimation.

PMID- 16638644
TI  - Oridonin inhibits cell growth by induction of apoptosis on human hepatocelluar
      carcinoma BEL-7402 cells.
AB  - The present study was undertaken to investigate the mechanisms of oridonin
      induced apoptosis on human hepatocellular carcinoma BEL-7402 cells. BEL-7402
      cells in culture medium in vitro were given different concentrations of oridonin.
      Cell proliferation was measured by MTT assay and [(3)H]-thymidine uptake, cell
      apoptotic rate was detected by flow cytometry (FCM), morphology of cell apoptosis
      was observed by Hoechst 33258 staining and DNA fragmentation. Caspase-3 as well
      as Bcl-2 and Bax expressions were detected by Western blotting. The results
      revealed that oridonin could inhibit the growth of BEL-7402 cells and cause
      apoptosis significantly, the suppression was both in time- and dose-dependent
      manner. Marked morphological changes of cell apoptosis were observed very clearly
      by Hoechst 33258 staining as well as DNA fragmentation analysis after the cells
      exposed to oridonin for 60h; Western blotting showed cleavage of the caspase-3
      zymogen protein (32-kDa) with the appearance of its 20-kDa subunit; Along with
      the apoptotic process Bcl-2 expression was down-regulated and Bax expression up
      regulated concurrently observed by Western blotting. We therefore conclude that
      oridonin can inhibit cell growth by induction of apoptosis in BEL-7402 cells via
      activation of caspase-3 as well as down-regulation of Bcl-2 and up-regulation of
      Bax expression. The results indicate that oridonin may be an important potential
      anti-hepatocellular carcinoma reagent.

PMID- 16638645
TI  - Association of NRAMP 1 gene polymorphism with susceptibility to tuberculosis in
      Taiwanese aboriginals.
AB  - BACKGROUND/PURPOSE: The human homologue of mice natural-resistance-associated
      macrophage protein 1 (Nramp 1) gene, NRAMP 1, has been reported to play a role in
      susceptibility to tuberculosis in humans. The aboriginal population in Taiwan has
      a five-fold higher prevalence of tuberculosis than people of Han ethnicity.
      Whether genetic factors such as NRAMP 1 polymorphism play a role in the
      prevalence of tuberculosis in Taiwanese aboriginals should be clarified. METHODS:
      NRAMP 1 polymorphism was studied using a case-control design of patients with
      tuberculosis, including subjects of Han (Hans) and aboriginal ethnicity in
      Hualien, eastern Taiwan. The polymorphisms of NRAMP 1 at loci INT4, D543N, 77
      385C/T, 3-UTR (CAAA) deletion and 5-(CA)n microsatellite markers were assessed by
      polymerase chain reaction on tissue DNA isolated from 105 aborigines and 110 Hans
      with tuberculosis. Comparable numbers of ethnically-matched controls were studied
      simultaneously. RESULTS: Two NRAMP 1 polymorphisms, INT4 and 5-(CA)n, were
      significantly associated with susceptibility to tuberculosis in aboriginals (p =
      0.0070 and p = 0.0031, respectively). However, no association was detected at the
      five loci of NRAMP 1 polymorphisms among Hans (p > 0.08). CONCLUSION: Genetic
      variation in NRAMP 1 may affect susceptibility to and increase risk for
      tuberculosis in Taiwanese aboriginals. Although environmental factors play an
      important role in tuberculosis infection, genetic factors such as NRAMP 1
      polymorphism may also contribute to the high prevalence of tuberculosis in
      Taiwanese aboriginals.

PMID- 16638646
TI  - Abdominal nontuberculous mycobacterial infection in a university hospital in
      Taiwan from 1997 to 2003.
AB  - BACKGROUND/PURPOSE: Abdominal nontuberculous mycobacterial infection is a rare
      condition. Continuous ambulatory peritoneal dialysis (CAPD)-associated
      peritonitis is the most common manifestation of infection due to nontuberculous
      mycobacteria (NTM). There are limited data on the clinical manifestations of
      nontuberculous mycobacterial infection. This study investigated the diagnostic
      features, clinical presentation, mycobacteriology, treatment and outcome of all
      abdominal NTM infections treated over a 7-year period at a major teaching
      hospital in Taiwan. METHODS: The medical records of all patients with a diagnosis
      of abdominal NTM infection from January 1997 through to December 2003 were
      retrospectively reviewed. RESULTS: All 11 patients with abdominal NTM infections
      identified during the 7-year period were included. Among these patients, six were
      male and five were female, with a mean age of 64.5 years. The disease manifested
      as peritonitis (9 patients, 82%), splenic abscess (1, 9%), or perirenal abscess
      (1, 9%). Most patients (73%) had underlying malignancy, most often hepatoma
      (45%). Immunocompromised status (liver cirrhosis, malignancy, acquired
      immunodeficiency syndrome) was noted in 10 patients (91%). None of our patients
      who developed NTM peritonitis had received CAPD. The peritoneal fluid appearance
      varied considerably, with no particular predominance of clear, turbid, bloody, or
      chylous findings. Rapidly growing mycobacteria were the major etiology (46%) of
      abdominal NTM infection, and Mycobacterium abscessus played a major role (27%).
      Overall, eight patients died, and only one patient survived longer than 1 year.
      Seven patients (64%) died before diagnosis. CONCLUSION: Abdominal NTM infection
      is frequently overlooked because of its rarity and nonspecific symptoms, with
      consequent delays in diagnosis and treatment. In immunocompromised patients with
      ascites from any cause (liver cirrhosis, malignant ascites, etc.), NTM
      peritonitis should be considered early in the differential diagnosis of symptoms
      including fever, abdominal pain and weight loss. The poor prognosis of abdominal
      NTM infection appears to be related to the severity of underlying conditions,
      most often malignancy.

PMID- 16638647
TI  - Pericardial fluid and serum levels of vascular endothelial growth factor and
      endostatin in patients with or without coronary artery disease.
AB  - BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) and endostatin are
      related to ischemic heart disease. This study investigated pericardial fluid and
      serum levels of VEGF and endostatin in patients with or without ischemic heart
      disease. METHODS: A total of 39 patients (24 patients in the CAD group with
      significant coronary artery disease; 15 patients in the non-CAD group without
      coronary artery disease) undergoing open heart surgery were enrolled. In the CAD
      group, patients were classified according to good coronary collateralization
      (Group A; n = 11) or poor coronary collateralization (Group B; n = 13).
      Pericardial fluid and serum samples were obtained at the time of surgery. VEGF
      and endostatin were measured by enzyme-linked immunosorbent assay. RESULTS: The
      levels of endostatin in both serum and pericardial fluid were significantly lower
      in the CAD group than in the non-CAD group (130.5 +/- 37.3 ng/mL vs. 172.4 +/-
      37.8 ng/mL and 119.0 +/- 25.0 ng/mL vs. 143.0 +/- 23.5 ng/mL). The concentration
      of serum VEGF in the CAD group (92.6 +/- 18.2 pg/mL) was significantly higher
      than that in the non-CAD group (75.2 +/- 22.3 pg/mL). The concentration of serum
      VEGF in Group A (100.1 +/- 20.7 pg/mL) was significantly higher than that in
      Group B (84.3 +/- 12.4 pg/mL). The levels of pericardial fluid VEGF, serum and
      pericardial fluid endostatin were not significantly different between Groups A
      and B. CONCLUSION: Patients with coronary artery disease have lower serum and
      pericardial fluid levels of endostatin and higher serum levels of VEGF. Serum
      level VEGF, but not endostatin, is associated with good or poor collateralization
      in patients with coronary artery disease.

PMID- 16638648
TI  - Endoscopic radial artery harvest for coronary artery bypass surgery.
AB  - BACKGROUND/PURPOSE: Coronary artery bypass grafting (CABG) provides better long
      term patency than percutaneous intervention in patients with significant coronary
      artery disease. The radial artery is the second most common arterial conduit used
      for CABG in Western countries. However, radial artery harvesting necessitates a
      large surgical wound and has gained few patients' acceptance in subtropical
      areas. This study investigated the use of the minimally invasive approach of
      endoscopic radial artery harvest for CABG, and the surgical results at the
      harvest site. METHODS: An endoscopic harvest program for radial arteries was
      implemented in this hospital in September 2003. During the first 12 months of the
      program until September 2004, 122 patients underwent the procedure. Preoperative
      evaluation included Allen's test and the modified palmar arch perfusion test. The
      age of patients ranged from 32 to 88 years old. Patients were excluded from
      participation if they had undergone recent transradial catheterization, had end
      stage renal disease or documented peripheral artery occlusive disease. The
      VasoView system was utilized for the procedure. Details of the surgical
      techniques used were recorded and analyzed. RESULTS: Using the endoscopic
      technique, 122 radial arteries were harvested successfully. The mean resting
      length of the harvested radial artery was 15.7 cm. No obvious arterial injury was
      visually confirmed. All radial arteries were used for CABG, except for two which
      were noted to have atherosclerotic plaques causing stenoses. Forty-seven patients
      presented with mild numbness over the dorsum of the thumb base, which improved
      significantly during the 3-month follow-up. No arterial insufficiency in the
      forearms or hands was noted. CONCLUSION: Endoscopic harvest of the radial artery
      is technically demanding, but excellent results can be achieved. The endoscopic
      approach can provide suitable conduits in a less invasive way than the open
      harvest technique.

PMID- 16638649
TI  - Predictive value of rapid shallow breathing index measured at initiation and
      termination of a 2-hour spontaneous breathing trial for weaning outcome in ICU
      patients.
AB  - BACKGROUND/PURPOSE: The rapid shallow breathing index (RSBI) is a weaning
      parameter usually measured at the start of a spontaneous breathing trial (SBT).
      This study investigated the value of RSBI measured at the beginning and
      termination of SBT as a predictor of weaning outcome. METHODS: RSBI was measured
      during the initial 1 minute (RSBI1) and at termination (RSBI2) of an SBT in 172
      patients recovering from acute respiratory failure. RESULTS: Weaning was
      successful in 106 patients and failed in 66 patients. Among the 66 patients with
      weaning failure, 12 required reintubation within 48 hours (extubation failure),
      and the remaining 54 patients could not be extubated after SBT (trial failure).
      There were no differences between RSBI1 in the three groups (69.4 +/- 27.5, 81.7
      +/- 24.4 and 75.5 +/- 26.5, respectively), but RSBI2 was significantly higher in
      patients with extubation failure (95.9 +/- 20.6) and trial failure (98.0 +/-
      50.0) than in patients with weaning success (64.6 +/- 26.3) (both p < 0.001).
      Logistic regression revealed that RSBI2 was superior to RSBI1 and various
      physiologic indices in predicting weaning outcome. For the 118 extubated
      patients, the mean area under the receiver operating characteristic curve for
      RSBI2 and RSBI1 was 0.83 and 0.63, respectively. Using a threshold value of 105,
      the sensitivity, specificity, accuracy and likelihood ratio for weaning outcome
      were 0.91, 0.25, 0.85 and 1.38 for RSBI2 and 0.89, 0.16, 0.60 and 1.06 for RSBI1,
      respectively. CONCLUSION: This study found that RSBI measured at the completion
      of SBT was superior to that measured at the start in predicting weaning outcome
      in critically ill patients.

PMID- 16638650
TI  - Clinical improvement following home parenteral nutrition in pediatric patients
      with intestinal failure.
AB  - BACKGROUND/PURPOSE: Home parenteral nutrition (HPN) is being increasingly used to
      treat children with intestinal failure. This study evaluated the long-term
      growth, outcome and complications in Taiwanese pediatric patients with intestinal
      failure who were treated with HPN. METHODS: This retrospective study included 27
      consecutive pediatric patients with intestinal failure who received long-term HPN
      between 1987 and 2002. These patients were categorized into two groups according
      to whether they had short bowel syndrome or a bowel motility disorder. Growth,
      prognosis and complications, including cholestasis, hypoglycemia, hyperglycemia
      and infections were compared between the two groups. RESULTS: The median age of
      starting HPN was significantly younger in patients with short bowel syndrome (5
      months) than in patients with motility disorders (1.9 years). The median duration
      of HPN treatment in the overall group was 13.5 months (range, 2.1-113.1 months);
      weight and height increased 1.7 +/- 2.3 and 1.0 +/- 1.6 in z score, respectively.
      The most common complications were cholestatic liver disease (52%), hypoglycemia
      (15%) and hyperglycemia (33%). All patients maintained stable serum glucose
      levels at follow-up. Cholestatic liver disease developed after 2.3 +/- 2.0 months
      of total HPN in 13 patients, which subsided after 9.7 +/- 6.9 months in 11
      patients, while two patients died. The mean incidence of central venous infection
      was 3.0 +/- 3.3 per 1000 HPN days. The most common pathogens were Staphylococcus
      spp. (50%) and Candida spp. (30.6%). CONCLUSION: HPN treatment can successfully
      provide a bridge to enteral nutrition in pediatric patients with intestinal
      failure. The metabolic disturbances and cholestasis are usually transient, but
      infection control is important throughout the period of HPN treatment.

PMID- 16638651
TI  - Factors related to meaning of life in Taiwanese women treated with in vitro
      fertilization.
AB  - BACKGROUND/PURPOSE: The meaning of life can be defined as a sense of a clear aim
      in life and a belief that one's daily activities are meaningful. Pregnancy is
      clearly an important aim of women who undergo in vitro fertilization (IVF)
      treatment. The purpose of this study was to evaluate the meaning of life and its
      related factors among women who underwent IVF treatment throughout the first
      treatment cycle until either pregnancy was achieved or when the attempt was
      abandoned. METHODS: This cross-sectional study was performed in a single medical
      center in Taiwan. A total of 149 subjects were recruited from women receiving IVF
      (n = 69) and women who had experienced IVF failure within the previous 1 year (n
      = 80). These women were classified into four subgroups according to their
      treatment stages: beginning of first IVF (n = 39); pregnancy/delivery (n = 22);
      continuing treatment (n = 64); and discontinuing treatment (n = 24). The Purpose
      in Life (PIL) test, a previously developed instrument designed to measure meaning
      of life, was administered to all patients at their follow-up IVF visit. RESULTS:
      The mean PIL score was 99.1 +/- 19.5, which indicated that all subjects had some
      degree of uncertainty regarding the meaning of life; however, no significant
      difference in PIL score was found among the four groups. Four factors were
      extracted from PIL by factor analysis, among which "existential frustration"
      (factor 4) was highest in the continuing group and those with a lower level of
      education; whereas "being in control" (factor 2 ) was lowest in women whose
      infertility had a female etiology. CONCLUSION: Treatment stage, educational
      level, and etiology of infertility were found to be factors influencing the
      meaning of life in women undergoing IVF.

PMID- 16638652
TI  - Renal cell carcinoma producing granulocyte colony-stimulating factor.
AB  - Severe neutrophilia caused by renal cell carcinoma secreting granulocyte colony
      stimulating factor (G-CSF) is a rare manifestation of renal cancer. A 70-year-old
      woman presented with a 2-year history of severe anemia, severe neutrophilia and
      elevated serum G-CSF, which completely resolved after radical nephrectomy.
      Histologic study revealed a histologically high-grade, stage pT1N0M0 renal cell
      carcinoma. Serum G-CSF level was elevated preoperatively and returned to normal
      postoperatively. Immunohistochemical study of the tumor tissue using anti-G-CSF
      monoclonal antibody revealed positive staining in the cancer cells. Careful
      follow-up of white blood cell count and physical examination for neck lymph node
      enlargement led to the timely identification of tumor recurrence 17 months after
      surgery, which resulted in prompt and successful salvage immunotherapy. In this
      case, G-CSF appeared to contribute to the leukocytosis, as both serum G-CSF level
      and white blood cell count closely correlated with the clinical tumor growth.
      White blood cell count should be closely monitored as an indicator of disease
      activity in patients with G-CSF-producing renal cell carcinoma.

PMID- 16638653
TI  - Detection of right to left shunt by transesophageal echocardiography in a patient
      with postoperative hypoxemia.
AB  - Intracardiac right to left shunt through a patent foramen ovale (PFO) may result
      in the development of hypoxemia after cardiac surgery. Cardiac tamponade and
      mechanical ventilation with high positive endexpiratory pressure are the most
      common factors responsible for enhancing intracardiac right to left shunt through
      a PFO. We report an 83-year-old woman with Stanford type A dissecting aneurysm
      who developed hypoxemia and paradoxical air embolism after reconstruction of
      ascending aorta and Bental's procedure. Transesophageal echocardiography (TEE)
      revealed right to left shunting via a PFO. Surgical closure of the PFO was done
      without delay. This case illustrates the role of TEE in prompt diagnosis of
      intracardiac right to left shunting through a PFO causing postoperative hypoxemia
      after cardiac surgery.

PMID- 16638654
TI  - Prolonged extracorporeal membrane oxygenation support for acute respiratory
      distress syndrome.
AB  - When all conventional treatments for respiratory failure in patients with acute
      respiratory distress syndrome (ARDS) have failed, extracorporeal membrane
      oxygenation (ECMO) can provide a chance of survival in these desperately ill
      patients. A 49-year-old male patient developed septic shock and progressive ARDS
      after liver abscess drainage. Venovenous ECMO was given due to refractory
      respiratory failure on postoperative day 6. Initially, two heparin-binding hollow
      fiber microporous membrane oxygenators in parallel were used in the ECMO circuit.
      Twenty-two oxygenators were changed in the first 22 days of ECMO support because
      of plasma leak in the oxygenators. Each oxygenator had an average life of 48
      hours. Thereafter, a single silicone membrane oxygenator was used in the ECMO
      circuit, which did not require change during the remaining 596 hours of ECMO. The
      patient's tidal volume was only 90 mL in the nadir and less than 300 mL for 26
      days during the ECMO course. The patient required ECMO support for 48 days and
      survived despite complications, including septic shock, ARDS, acute renal
      failure, drug-induced leukopenia, and multiple internal bleeding. This patient
      received an unusually long duration of ECMO support. However, he survived,
      recovered well, and was in New York Heart Association functional class I-II, with
      a forced expiratory volume in 1 second of 81% of the predicted level 18 months
      later. In conclusion, ECMO can provide a chance of survival for patients with
      refractory ARDS. The reversibility of lung function is possible in ARDS patients
      regardless of the severity of lung dysfunction at the time of treatment.

PMID- 16638655
TI  - Imaging findings in mucin-producing carcinoma of the gallbladder.
AB  - Mucin-producing carcinoma of the gallbladder is rare, and its imaging features
      have not been well documented. Its symptoms and signs are nonspecific and the
      prognosis of the disease is poor. We present a 73-year-old male with mucin
      producing carcinoma of the gallbladder, emphasizing its imaging features on
      ultrasound, computed tomography and magnetic resonance imaging. The tumor usually
      presents as a cauliflower-like soft tissue mass with small calcified spots in the
      gallbladder wall and some laminated high viscosity fluid inside the gallbladder
      cavity. Recognition of these features can provide clues to the diagnosis of mucin
      producing carcinoma of the gallbladder.

PMID- 16638656
TI  - Tension pneumoperitoneum following upper gastrointestinal endoscopy.
AB  - Tension pneumoperitoneum is a potentially lethal complication of numerous
      iatrogenic procedures, including upper gastrointestinal (UGI) endoscopy. We
      report a 69-year-old man with UGI bleeding who developed tension pneumoperitoneum
      and cardiac arrest after UGI endoscopy. He was successfully resuscitated with
      needle decompression. Emergency surgery revealed a perforated gastric ulcer, and
      subtotal gastrectomy with Billroth II anastomosis was performed. Recovery was
      smooth and he was discharged from the hospital 18 days later. Tension
      pneumoperitoneum should be suspected in all patients who develop circulatory
      collapse with acutely distended abdomen after UGI endoscopy. Early identification
      relies on a high index of suspicion. Prompt treatment with needle decompression
      should not be delayed for confirmatory radiography once the clinical diagnosis is
      made.

PMID- 16638657
TI  - Three novel EXT1 and EXT2 gene mutations in Taiwanese patients with multiple
      exostoses.
AB  - Multiple osteochondromatosis, also known as hereditary multiple exostoses (HME),
      is an inherited autosomal dominant disorder characterized by the presence of
      multiple exostoses on the long bones. These exostoses are benign cartilaginous
      tumors (enchondromata). Three different exostosis (EXT) loci on chromosomes 8q
      (exostosin 1, EXT1), 11p (exostosin 2, EXT2) and 19p (exostosin 3, EXT3) have
      been reported. Recently, the EXT1 and EXT2 genes were identified by positional
      cloning. Using polymerase chain reaction and direct sequencing, we analyzed the
      EXT1 and EXT2 genes in three familial cases and one sporadic case of HME in
      Taiwanese patients. We found three novel mutations (S277X in the EXT1 gene, and
      G194X and 939+1G>A in the EXT2 gene) and a known mutation (Q172X in the EXT2
      gene). Mutation analysis in families with HME allows for genetic counseling and
      prenatal diagnosis.

PMID- 16638658
TI  - Ethyl acetate extract from black tea prevents neuromuscular blockade by botulinum
      neurotoxin type A in vitro.
AB  - Botulinum neurotoxin produced by Clostridium botulinum is the strongest
      neurotoxin and causes botulism in mammals. The current study aimed to find an
      inactivator for botulinum neurotoxin in black, oolong, roasted, and green teas.
      The ability of the four teas to inactivate the neuromuscular blocking action of
      botulinum neurotoxin was determined. Water extracts from black, oolong, and
      roasted teas protected against the toxicity of botulinum neurotoxin type A in
      mouse phrenic nerve-diaphragm preparations. The order of potency of the water
      extracts was black tea > oolong tea > roasted tea > green tea (no effect). The
      effects of several organic solvent extracts of black tea water extract were
      examined, and the order of potency was ethyl acetate extract > butanol extract =
      remaining extract > chloroform extract (no effect). Ethyl acetate extracts from
      oolong, roasted, and green tea water extracts also exhibited a stronger
      protecting effect than chloroform, butanol, and remaining extracts from these
      teas, but they had weaker protective effect than ethyl acetate extract from black
      tea water extract. These protective effects occurred only when each extract was
      pre-mixed with the toxin before the assay, and they were not modified by mixing
      each extract with bovine serum albumin (BSA) before adding the toxin. These
      results indicate that ethyl acetate extract from black tea is the best source for
      searching for tea-derived inactivating substance(s) of botulinum neurotoxin.

PMID- 16638659
TI  - Comparison of the antioxidant activity of roasted tea with green, oolong, and
      black teas.
AB  - Although the antioxidant properties of green, oolong, and black teas have been
      well studied, antioxidant activity has not been examined in roasted tea.
      Therefore, in the current studies, we investigated the antioxidant activity of
      roasted tea in comparison with those of green, oolong, and black teas. Using
      water extracts of the various teas, we examined the total phenolic content as
      well as the antioxidant activities, including the reducing power, the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and the inhibition
      of hemolysis caused by 2,2'-azo-bis(2-amidinopropane) dihydrochloride (AAPH)
      induced lipid oxidation in erythrocyte membranes. The roasted tea contained lower
      levels of total phenolics than green, oolong, or black tea (green tea > oolong
      tea > black tea > roasted tea). The relative reducing power and DPPH scavenging
      activity decreased in the following order: green tea > roasted tea > oolong tea >
      black tea. Also, green tea was more effective against AAPH-induced erythrocyte
      hemolysis than other teas (green tea>roasted tea = oolong tea = black tea). These
      results suggest that roasted tea is beneficial to health, in humans, because of
      its high antioxidant activity.

PMID- 16638660
TI  - Relation of smoking, physical activity and living residence to body fat and fat
      distribution in elderly men in Greece.
AB  - It is well-documented that body fat and body fat distribution are related to
      increased risk for cardiovascular disease, hyperinsulinaemia, and diabetes
      mellitus. The purpose of this study was to investigate the impact of smoking
      status, physical activity and place of living on body fat and fat distribution of
      Greek elderly men. The participants were 144 elderly men of mean age 71.78 +/-
      6.39 years, who were free-living individuals, in Thessaloniki (104 subjects) and
      in the suburbs (40 subjects). According to our results, 23.9% of men who
      participated in the study were smokers. No association was found between
      skinfolds, skinfold ratio and physical activity or smoking. It is worth to
      mention that a triple percentage of younger elders (60-75 years) smoked, compared
      to the older ones. This finding could possible explain the absence in
      anthropometric differences between elderly smokers and non-smokers. Intervention
      programs aiming to yield information about changing the various modifiable risk
      factors in the elderly are needed.

PMID- 16638661
TI  - Effect of high stearic acid containing fat on markers for in vivo lipid
      peroxidation.
AB  - The objective of this study was to determine the effect of high stearic acid (SA)
      diets versus high polyunsaturated fatty acid (PUFA) diets on several measures of
      lipid peroxidation in vivo. Sprague-Dawley rats were fed diets that differed only
      in the fat source (8% by weight) for 19 weeks. High SA fats were beef tallow (BT)
      and cocoa butter (CB), high PUFA fats were soybean oil (SO) and menhaden oil
      (MO). Urine was analyzed for lipophilic aldehydes, the secondary products of
      lipid peroxidation, by HPLC. Decreases (P<0.05) were found for 4 nonpolar
      lipophilic aldehydes and related carbonyl compounds (NPC) and 4 polar lipophilic
      aldehydes and related carbonyl compounds (PC) when the BT-fed group was compared
      to the SO-fed group. Decreases were also found to be significant for total NPC
      (P<0.01) and total PC (P<0.05) between BT and SO-fed groups. Serum increase in
      resistance to oxidation (P<0.01) was found in the BT group when compared to the
      SO group. The differences in urine and serum measurements in the present
      experiment indicate lower level of lipid peroxidation in vivo due to the
      consumption of high SA containing BT diet compared to high PUFA containing SO
      diet without raising serum triglycerides and cholesterol levels significantly for
      the BT-fed groups.

PMID- 16638662
TI  - Determination of benzo[a]pyrene in charcoal grilled meat samples by HPLC with
      fluorescence detection.
AB  - In this study, an HPLC procedure for the quantitative determination of
      benzo[a]pyrene (BaP) in charcoal grilled meat samples has been applied to the
      analysis of the Turkish meat samples. The grilled meat samples were first treated
      in alkaline medium, then BaP was extracted into n-hexane phase, purified on XAD-2
      column and eluted with n-hexane/dichloromethane mixture (9:1,v/v). Separation and
      quantitative determination of BaP has been carried out by a C18 reversed phase
      column mounted HPLC with a fluorescence detection of 254-355 nm (excitation
      emission). The BaP levels determined in grilled and over-grilled lamb and beef
      meats were 43.80 +/- 1.80 microg/kg, 31.33 +/- 0.94 microg/kg and 62.60 +/- 3.72
      microg/kg, 37.60 +/- 3.84 microg/kg, respectively.

PMID- 16638663
TI  - Physicochemical and nutritional characteristics of the fruit of Zizyphus
      sonorensis S. Wats (Rhamnaceae).
AB  - The nanche de la costa (Zizyphus sonorensis) fruit was partially characterized by
      physicochemical and nutritional analyses. This fruit has a homogenous size and
      color and low moisture content (47 g/100 g). The content of tannins and nickel of
      the edible portion might limit its use. However, nanche de la costa has important
      characteristics and potential to be considered as a food or feed source. The
      remarkable characteristics of the edible portion are high content of total (35
      g/100 g) and soluble (0.6 g/100 g) dietary fiber, high level of copper (0.53
      mg/100 g), iron (10 mg/100 g) and zinc (4.2 mg/100 g). The seed was distinguished
      by its high content of total dietary fiber (82.1 g/100 g), calcium (540 mg/100
      g), copper (0.54 mg/100 g), chromium (1.1 mg/100 g) and zinc (4.5 mg/100 g). The
      moisture value is given in fresh weight basis and all other values are in dry
      weight basis.

PMID- 16638664
TI  - Antioxidant activities of New Zealand-grown tomatoes.
AB  - The objective of this study was to compare the antioxidant activities, total
      phenolics, lycopene and ascorbic acid content of four commercial tomato cultivars
      (Excell, Tradiro, Flavourine and Campari) of New Zealand, grown under similar
      hydroponic conditions. The mean antioxidant activity of the four cultivars, as
      measured with the ABTS radical decolourization assay, ranged from 2329 to 3268
      micromole TEAC/100 g dry matter (DM) in the hydrophilic extracts and from 178 to
      303 micromole TEAC/100 g DM in the lipophilic extracts. The major antioxidant
      components per 100 g DM were phenolics (343-451 mg gallic acid equivalents in
      hydrophilic extract and 53-74 mg gallic acid equivalents in lipophilic extract),
      flavonoids (175-204 mg rutin equivalents), ascorbic acid (153-195 mg) and
      lycopene (33-54 mg). Ascorbic acid and flavonoids were found to contribute 28-38%
      and 29-34%, respectively, to the antioxidant activity of the hydrophilic extract
      of tomatoes. The results showed that the smallest cultivar (Campari) had
      significantly (P < 0.05) higher antioxidant activities, total phenolics and
      flavonoids than the larger sized cultivars (Excell, Tradiro and Flavourine). This
      could be attributed to the significantly (P < 0.05) higher surface area/volume
      ratio of the small cultivar (0.15) when compared with the large-sized cultivars
      (0.10-0.12). The tomato cultivar (Flavourine) with a brighter red colour (higher
      a*/b* value), had a higher lycopene content as well, which suggests that the
      a*/b* value of tomatoes can be used as an indicator of their lycopene content.
      The phenolics (r = 0.84**) and flavonoids (r = 0.88**) were significantly related
      to the antioxidant activity of the hydrophilic extract, which suggests that
      measurement of total phenolics or flavonoids can be used as indicators of the
      antioxidant activity of tomatoes.

PMID- 16638665
TI  - Intraplacental retinol distribution.
AB  - With the objective of evaluating intraplacental vitamin A distribution, 234
      placental samples were collected, corresponding to six samples from each of the
      placentas analyzed: two from the lateral maternal portion, one from the central
      maternal portion, two from the lateral fetal portion, and one from the central
      fetal portion. Samples were obtained from 39 adult puerperal mothers with low
      risk pregnancies, without vitamin A deficiency or night blindness. Retinol
      content determination was achieved through spectrophotometry. Retinol values
      obtained for each region were correlated with the most probable value for each
      placenta (P < 0.001). Despite differences in retinol content between samples,
      statistical data analysis showed that intra-tissue variation had no influence on
      the conversion of data into information. Consequently, any portion of the
      placenta may be used for retinol level determination purposes, due to the
      correlation between all portions and the most probable value. The findings of the
      present study represent an advance for surveys intending to incorporate the
      collection and dosage of placental vitamin A levels into their analyses, thus
      increasing the arsenal of pre-pathological or subclinical vitamin A deficiency
      markers, which can allow for earlier intervention on the maternal-infant group.

PMID- 16638666
TI  - Blood pressure lowering effect of olive is mediated through calcium channel
      blockade.
AB  - Olive (Olea europea) is used in traditional medicine as a remedy for
      hypertension. The aqueous-methanolic crude extract of O. europea fruit (OeF.Cr)
      was studied in anaesthetized rats and its possible mechanism was elucidated using
      isolated cardiovascular preparations. Intravenous administration of OeF.Cr
      produced a dose-dependent (30-100 mg/kg) fall in arterial blood pressure in
      normotensive anaesthetized rats. This effect remained unaltered in atropinized
      animals. In the in vitro studies OeF.Cr (0.1-3.0 mg/ml) inhibited spontaneously
      beating guinea-pig atria. Moreover, it relaxed K+ and/or phenylephrine-induced
      contractions of rabbit aortic preparations over a dose range of 0.1-3.0 mg/ml,
      suggesting calcium channel blockade (CCB). The CCB effect was confirmed when
      pretreatment of the vascular preparations with OeF.Cr produced a dose-dependent
      rightward shift of the Ca2+ dose-response curves, similar to verapamil. These
      results suggest that the blood pressure lowering effect of olive is mediated
      through CCB, justifying its use in hypertension.

PMID- 16638678
TI  - The influence of different plasticizers and polymers on the mechanical and
      thermal properties, porosity and drug permeability of free shellac films.
AB  - The effect of triethyl citrate (TEC) and different molecular weights and
      concentrations of polyethylene glycol (PEG), in addition to the effect of
      different water-soluble polymers and dispersions at different levels,
      hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), carbomer 940,
      polyvinyl alcohol (PVA), ethyl cellulose (EC), on the mechanical and thermal
      properties, drug permeability, and porosity of free shellac films were
      investigated. Shellac films were cast from aqueous solutions, and their
      mechanical properties were studied by tensile test. Thermal analyses were
      performed using differential scanning calorimetry (DSC). The results showed that
      the addition of plasticizer caused a decrease in both elastic modulus and glass
      transition temperature (T(g)) and an increase in elongation at break of free
      shellac films. This effect was related to the concentrations of plasticizers.
      Different molecular weights of PEGs have different plasticization
      mechanisms.Moreover, the incorporation of different amounts of HPMC, MC, or
      carbomer in free shellac films caused an increase in the flexibility, decrease in
      T(g), and a marked increase in drug permeability of free shellac films, whereas
      the addition of PVA caused a decrease in flexibility and drug permeability and an
      increase in T(g). Addition of EC resulted in a slight decrease of the elasticity
      and a small decrease in drug permeability. However it does not show a
      considerable effect on the T(g). In addition, it was found that the drug
      permeability is directly related to the mechanical properties and T(g) of shellac
      films.

PMID- 16638679
TI  - Pharmacokinetic, tissue distribution, and excretion of puerarin and puerarin
      phospholipid complex in rats.
AB  - Puerarin is a potential therapeutic agent for cardiovascular diseases. But its
      poor oral bioavailability restricts its clinical application. In present study,
      as an evaluation of a formulation to improve the bioavailability of the drug,
      puerarin and its phospholipid complex were given to rats by intragastrically
      (i.g.) administration to compare pharmacokinetic, tissue distribution, and
      excretion. Serum samples were obtained at designated times after a single oral
      dose of 400 mg/kg puerarin or its complex. Tissue samples (heart, liver, spleen,
      kidney, lung, and brain), urine, and feces were collected and analyzed by a
      sensitive and specific high performance liquid chromatography (HPLC) method after
      i.g. administration of puerarin or its phospholipid complex. Compartmental and
      non-compartmental analyses were applied to the serum concentration versus time
      data. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic
      software package. An open two-compartment, first-order model was selected for
      pharmacokinetic modeling. The results showed that after i.g. administration of
      400 mg/kg puerarin and its phospholipid complex (equivalent to 400 mg/kg of
      puerarin), the pharmacokinetic parameters of the two formulations were different.
      The serum concentrations reached peaks at 0.894+/-0.521 h and 0.435+/-0.261 h,
      respectively, indicating the complex was more readily absorbed in serum than
      puerarin. The maximum concentrations for puerarin and its complex were 1.367+/
      0.586 mg.L(-1) and 2.202+/-1.28 mg.L(-1) and AUC were 5.779+/-1.662 mg.h. L(-1)
      and 8.456+/-0.44 mg.h L(-1), respectively, indicating a higher bioavailability
      for the complex. The widely distribution characteristics of puerarin and its
      complex in tissues post-i.g. administration was identical and in a descending
      order as follows: lung, kidney, liver, heart, spleen, and brain. However, the
      amount was different. Puerarin distribution was higher in heart, lung, and brain
      after administering the complex. The cumulative 72 h urinary excretion of
      puerarin after i.g. administration of puerarin and its complex accounted for
      1.05%, 1.11% of the administered dose, respectively. The cumulative feces
      excretion of puerarin was 32.3% and 25.5%. To sum up, oral administration of
      puerarin phospholipid complex modified the pharmacokinetics and tissue
      distribution of puerarin and it could be an effective oral formulation for
      puerarin.

PMID- 16638680
TI  - Effect of nerodilol and carvone on in vitro permeation of nicorandil across rat
      epidermal membrane.
AB  - The objective of the study was to investigate the effect of nerodilol and carvone
      on the in vitro transdermal delivery of nicorandil so as to fabricate a membrane
      moderated transdermal therapeutic system. The in vitro permeation studies were
      carried across the rat epidermal membrane from the hydroxypropyl methylcellulose
      (HPMC) gels (prepared with 70:30 v/v ethanol-water) containing selected
      concentrations of a terpene such as nerodilol (0%w/w, 4%w/w, 8%w/w, 10%w/w, or
      12%w/w) or carvone (0%w/w, 4%w/w, 8%w/w, 12%w/w, or 16%w/w). The amount of
      nicorandil permeated (Q(24)) from HPMC gel drug reservoir without a terpene was
      3424.6+/-51.4 microg/cm(2), and the corresponding flux of the drug was 145.5+/
      2.2 microg/cm(2). h. The flux of nicorandil increased with an increase in terpene
      concentration in HPMC gel. It was increased ranging from 254.9+/-3.1 to 375.7+/
      3.2 microg/cm(2).h or 207.6+/-4.7 to 356.7+/-15.3 microg/cm(2). h from HPMC gels
      containing nerodilol (4%w/w to 12%w/w) or carvone (4%w/w to 16%w/w),
      respectively. Nerodilol increased the flux of nicorandil by about 2.62-folds
      whereas carvone increased the flux of the drug by about 2.49-folds across the rat
      epidermal membrane. The results of the Fourier Transform Infrared (FT-IR) study
      indicated that the enhanced in vitro transdermal delivery of nicorandil might be
      due to the partial extraction of stratum corneum lipids by nerodilol or carvone.
      It was concluded that the terpenes, nerodilol and carvone, produced a marked
      penetration enhancing effect on the transdermal delivery of nicorandil that could
      be used in the fabrication of membrane-moderated transdermal therapeutic systems.

PMID- 16638681
TI  - Formulation of a fast-dissolving ketoprofen tablet using freeze-drying in
      blisters technique.
AB  - The aim of this work was to develop a ketoprofen tablet which dissolve-rapidly in
      the mouth, therefore, needing not be swallowed. The solubility and dissolution
      rate of poorly water-soluble ketoprofen was improved by preparing a lyophilized
      tablet (LT) of ketoprofen using freeze-drying technique. The LT was prepared by
      dispersing the drug in an aqueous solution of highly water-soluble carrier
      materials consisting of gelatin, glycine, and sorbitol. The mixture was dosed
      into the pockets of blister packs and then was subjected to freezing and
      lyophilization. The saturation solubility and dissolution characteristics of
      ketoprofen from the LT were investigated and compared to the plain drug and the
      physical mixture (PM). Results obtained showed that the increase in solubility of
      ketoprofen from LT matrix, nearly three times greater than the solubility of the
      plain drug, was due to supersaturation generated by amorphous form of the drug.
      Results obtained from dissolution studies showed that LT of ketoprofen
      significantly improved the dissolution rate of the drug compared with the PM and
      the plain drug. More than 95% of ketoprofen in LT dissolved within 5 min compared
      to only 45% of ketoprofen plain drug dissolved during 60 min. Initial dissolution
      rate of ketoprofen in LT was almost tenfold higher than that of ketoprofen powder
      alone. Crystalline state evaluation of ketoprofen in LT was conducted through
      differential scanning calorimetry (DCS) and x-ray powder diffraction (XRPD) to
      denote eventual transformation to amorphous state during the process. Scanning
      electron microscopic (SEM) analysis was performed and results suggest reduction
      in ketoprofen particle size.

PMID- 16638682
TI  - Design and evaluation of soluble ocular drug insert for controlled release of
      ciprofloxacin hydrochloride.
AB  - PURPOSE: Soluble ocular inserts of ciprofloxacin hydrochloride were prepared with
      the aim of achieving once a day administration. DESIGN: Drug reservoir was
      prepared using natural hydrophilic polymer viz. gelatin while rate-controlling
      membrane was prepared using hydrophobic ethyl cellulose. Ocular inserts were
      evaluated for their physicochemical parameters like thickness, weight uniformity,
      drug content, percent moisture loss, and percent moisture absorption. The in
      vitro drug release studies were carried out using Bi-chambered donor receiver
      compartment model. Since targeted prolong release was observed in formulation CF2
      and CF5, these formulations were further subjected to in vivo drug release study
      using rabbits as an animal model. In vitro drug release kinetic data was treated
      according to Zero, First, and Higuchi kinetics to access the mechanism of drug
      release. RESULTS: Correlation between in vitro and in vivo drug release was found
      to be strong revealing the efficacy of the formulation. CONCLUSION: Formulation
      CF5 has achieved target of present study such as increase residence time, prolong
      drug release, reduction in frequency of administration, and, thus may improve the
      patient compliance.

PMID- 16638683
TI  - Fluidity and tableting characteristics of a powder solid dispersion of the low
      melting drugs ketoprofen and ibuprofen with crospovidone.
AB  - A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which
      possess low melting points, plus crospovidone (CrosPVP), have good fluidity
      characteristics and can be used to formulate tablets. Tablets of KP or IP in the
      SD of adequate hardness within a narrow weight range can be prepared by direct
      compression. Addition of microcrystalline cellulose (MCC) resulted in greater
      hardness characteristics and less variation in tablet weight. Forces during the
      tableting process were measured with a tableting process analyzer (TabAll)
      equipped with a single-punch for determining capping and sticking properties
      during the tableting process. Pressure transmission ratio from the upper to the
      lower punch and die wall force were increased by adding 1% magnesium stearate
      (MS) to the SD. Ejection force decreased when MS was added to the SD. When
      tablets of the IP SD were prepared without excipient, scraper pressure (SP) was
      large, resulting in sticking. However, addition of 1% MS, lowered the SP value
      and eliminated sticking. Thus, an SD of compounds with a low melting point such
      as KP or IP is suitable for tablet manufacture by direct compression with the
      addition of 1% MS.

PMID- 16638684
TI  - Development and validation of a rapid HPLC method for the determination of
      ketotifen in pharmaceuticals.
AB  - In the present study, a simple, sensitive, rapid, and stability-indicating high
      performance liquid chromatographic (HPLC) method with ultraviolet detection for
      the analysis of ketotifen was developed and validated. The method was applied to
      the determination of ketotifen in pharmaceutical formulations (tablets and
      syrups). The HPLC method utilized isocratic elution technique with a reversed
      phase C8 column, detection at 297 nm and a mixture of methanol, triethylamine
      phosphate buffer (pH 2.8; 0.04 M), and tetrahydrofuran (43: 55: 2, v/v/v) as
      mobile phase at a flow rate of 1.2 mL/min. Total analysis time was about 7 min
      with typical retention time of ketotifen of about 5 min. The method was validated
      for selectivity, linearity, accuracy, and precision following International
      Conference of Harmonization, 1996 (ICH) recommendations. Due to its simplicity
      and accuracy, the method can be used for routine quality control analysis.

PMID- 16638685
TI  - The influence of drug-excipient and drug-polymer interactions on butt adhesive
      strength of ranitidine hydrochloride film-coated tablets.
AB  - The influence of fillers and polymeric films on adhesive strength of
      hydroxypropyl methylcellulose (HPMC) and Eudragit E100 films coated on ranitidine
      HCl tablets containing either spray-dried rice starch (SDRS) or lactose
      monohydrate as fillers after storage at 45 degrees C/75% RH for four weeks was
      investigated by the use of butt adhesion technique. The adhesive strength of film
      coated tablets of fillers without drug was found to slightly decrease after
      storage. In contrast, the adhesive strength of drug-containing film-coated
      tablets significantly reduced, the degree of which was higher for Eudragit E100
      than HPMC. Physicochemical characterization by employing differential scanning
      calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS) revealed that the drug was obviously incompatible with lactose and
      possibly mild interaction with Eudragit E100 was suggested. The results indicated
      that the adhesive strength of film-coated tablets would be affected not only by
      the drug-excipient interaction, but also by the drug-polymeric film interaction.

PMID- 16638686
TI  - Formulation and in vitro evaluation of bisphosphonate loaded microspheres for
      implantation in osteolysis.
AB  - Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with
      alendronate sodium (AS) were prepared for orthopedic as well as dental
      applications. In orthopedics the aim was to make the total joint prostheses stay
      in the body for a long time without causing bone tissue loss, while in dentistry
      it was aimed to treat the alveolar bone resorption caused by periodontitis and
      also to make the dental treatment using implants easier by reducing the bone loss
      in patients with osteoporosis. Solvent evaporation method was used to prepare AS
      loaded PLGA microspheres and emulsion polimerization method was used to prepare
      AS loaded chitosan microspheres. Particle size, loading efficacy, surface
      characteristics, and in vitro release characteristics were examined on prepared
      formulations. After the examination of the scanning electron microscopy
      photographs of microspheres, chitosan microspheres were observed to have
      spherical structure and smooth surface characteristics while PLGA microspheres
      were observed to have spherical porous surface structure. Loading efficacy was
      found to be 3.30% for chitosan microspheres and 7.70% for PLGA microspheres. It
      was observed that 85% of AS had been released at the end of the third day from
      chitosan microspheres whereas 58% was released at the end of the fifth day from
      PLGA microspheres. It was found that chitosan microspheres gave first order
      release while PLGA microspheres gave zero order release.

PMID- 16638687
TI  - Preparation and in vitro release of dual-drug resinates containing equivalent
      content dextromethorphan and diphenhydramine.
AB  - The dual-drug resinate containing equivalent content of dextromethorphan
      hydrobromide (DTM) and diphenhydramine hydrochloride (DPH) was developed and
      characterized. To achieve this specific resinate, a procedure of simultaneous
      dual-drug loading using loading solutions composed of different proportions of
      DTM and DPH was performed and a dual-drug loading diagram was constructed to
      determine the equivalent drug loading solution (ELS) and also the estimated
      equivalent drug content (EQC). The effects of resin crosslinkage, overall drug
      concentration of the loading solution, and temperature during drug loading on the
      values of ELS and EQC were assessed. The increased overall drug concentration
      from 0.25 to 1.0% w/v elevated the EQC values from 18 to 35% w/w for low
      crosslinked resins (Dowex 50 W x 2 and x 4), and from 18 to 27% w/w for high
      crosslinked resin (Dowex 50 W x 8). It also changed the values of ELS from 0.50
      to 0.48 for the low crosslinked resins, and 0.50 to 0.55 for the high crosslinked
      resin. For the high crosslinked resin, the applied heat from 35 to 65 degrees C
      further increased the values of EQC from 27 to 32% w/w, and changed the values of
      ELS in the reverse direction from 0.55 to 0.48. However, the heat did not exert
      significant effects on the values of EQC and ELS for the low crosslinked resins.
      Different batches of dual-drug resinates prepared from the determined ELS
      provided the resultant resinates with equivalent contents of DTM and DPH which
      were very close to the estimated EQC. The drug release from the resinates was
      performed in 0.05, 0.1, 0.2, and 0.4 N of KCl solutions. The increased ionic
      strength generally accelerated the release of both drugs except for 0.4 N KCl
      solution in which the drug release from the resinates of high crosslinkage was
      decreased. The congestion on the outward movement of drugs through the high
      crosslinked matrix might cause the delay of drug release. In conclusion, the
      release study demonstrated that the dual-drug resinate using a suitable
      crosslinked resin could be used for extended delivery of two combined drugs with
      the equivalent therapeutic dose.

PMID- 16638688
TI  - Formulation, quality control and shelf life of the experimental cytostatic drug
      cyclopentenyl cytosine.
AB  - This paper describes the formulation and quality control of an aqueous sterilized
      formulation of the experimental cytostatic drug cyclopentenyl cytosine (CPEC) to
      be used in Phase I/II clinical trials. The raw drug substance was extensively
      tested. A High Pressure Liquid Chromotography (HPLC) method was validated for the
      quality control of the formulated product. The aqueous formulation was found to
      be stable for at least 2 years at 2-8 degrees C. Sterilization (15 min at 121
      degrees C) showed no influence on drug stability. The results show that CPEC can
      be formulated in an aqueous solution. The described HPLC method is a useful tool
      in the pharmaceutical quality control.

PMID- 16638692
TI  - Optimizing management of distal ulcerative colitis.

PMID- 16638693
TI  - Relationship among serum pepsinogens, serum gastrin, gastric mucosal histology
      and H. pylori virulence factors in a paediatric population.
AB  - OBJECTIVE: Serum pepsinogens and gastrin have been proposed as markers of
      gastritis, but have seldom been studied in children. In this study the aim was to
      identify host- and Helicobacter pylori-related factors linked to variations in
      serum gastrin, PGI, PGII, and to evaluate the potential of these biomarkers for
      diagnosing gastritis, whether H. pylori-associated or not. MATERIAL AND METHODS:
      Ninety-two dyspeptic children referred for endoscopy (peptic ulcer exclusion)
      were included in the study. H. pylori status (urease, culture, histology) was
      assessed, and genotype determined (PCR) in H. pylori-positive subjects. Serum
      gastrin, PGI and PGII levels were measured by standard radioimmunoassay (RIA).
      RESULTS: PGI and PGII levels were significantly higher in H. pylori-positive
      subjects (p=0.007; p=0.012, respectively). Gastrin levels were significantly
      higher in H. pylori-negative subjects (p=0.035). PGI and PGII were associated
      significantly with higher antrum inflammation scores (p=0.002; p=0.016,
      respectively); only PGI was associated with age, after controlling for
      inflammation (p=0.033) and for activity (p=0.037). The contribution of virulence
      factors could not be assessed owing to the low number of virulent strains. After
      multivariate analysis, only antrum inflammation was independently associated with
      PGI level (p=0.012). Receiver operating characteristic (ROC) analysis showed a
      low PGI and PGII discriminant power for predicting antrum inflammation.
      CONCLUSIONS: Pepsinogen levels as measured in this study seem predominantly to
      reflect antral inflammation, but they are not an effective screening test for
      gastritis (H. pylori-positive or -negative) in dyspeptic children.

PMID- 16638694
TI  - Interaction between Helicobacter pylori infection and untreated coeliac disease
      on gastric histological pattern.
AB  - OBJECTIVE: Helicobacter pylori infection is the major agent of gastric damage.
      Coeliac disease may affect the morphology and function of the entire
      gastrointestinal tract from the stomach to the colon. The aim of this study was
      to assess the gastric histological pattern in patients with H. pylori and
      untreated coeliac disease. MATERIAL AND METHODS: We retrospectively enrolled 183
      H. pylori-positive patients with (85, group A) and without (98, group B)
      untreated coeliac disease. The groups were similar for age, gender and smoking
      habit, and all the patients came from the same geographical area. Histological
      evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in
      the corpus). Gastric damage was classified according to the modified Sydney
      System. Diagnosis of H. pylori infection was based on positivity to histology.
      The chi-square test was used to assess differences between groups. A p-value
      <0.05 was considered significant. RESULTS: Group A showed a significantly higher
      prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A
      significantly lower prevalence of atrophic gastritis was observed in group A
      compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of
      chronic superficial gastritis, activity degree and intestinal metaplasia was
      similar between the two groups. CONCLUSIONS: In patients with H. pylori
      infection, untreated coeliac disease could represent a risk factor for follicular
      gastritis and is associated with a lower prevalence of atrophic gastritis. The
      complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2
      balance in the gastric mucosa could explain these results.

PMID- 16638695
TI  - Concomitant variations of gastric tone and duodenal motility in humans: results
      of a placebo-controlled study assessing octreotide and sumatriptan.
AB  - OBJECTIVE: To describe the concomitant effects of octreotide and sumatriptan on
      fundic tone and duodenal phase III activity. MATERIAL AND METHODS: A double-blind
      study was performed in nine volunteers, studied for 2 h after receiving 50 microg
      octreotide, 6 mg sumatriptan or placebo. Fundic tone variations were assessed by
      barostat while antroduodenal motility was studied concomitantly using manometry.
      RESULTS: A rapid increase in intrabag volume was observed in all but one subject
      after both sumatriptan and octreotide administration, while only two subjects
      exhibited a volume variation after placebo, p<0.01. A significant decrease in the
      number of phasic contractions was observed after octreotide, while sumatriptan
      reduced only wave amplitudes (p<0.05). A total of 13 concomitant duodenal phase
      III-like activities were observed in the duodenum after octreotide, 3 after
      sumatriptan and 4 after placebo, all followed by spontaneous fundic relaxation
      with disappearance of phasic contractions, p<0.05. Spontaneous phase III
      activities were different from phases III-like activities after octreotide in
      velocity and duration (p<0.05). CONCLUSIONS: Octreotide induced concomitant
      fundic relaxation, disappearance of phasic contractions and duodenal phase III
      like activity. Sumatriptan relaxed the proximal stomach and reduced the amplitude
      of fundic phasic contractions without affecting concomitant antroduodenal phase
      III activity.

PMID- 16638696
TI  - Pressure-induced gastric accommodation studied with a new distension paradigm.
      Abnormally low accommodation rate in patients with functional dyspepsia.
AB  - OBJECTIVE: A new distension paradigm, by which the gastric volume response to
      ramp-tonic distension can be analysed in detail, has been developed. The aim of
      this study was to investigate the applicability of this new paradigm in man, and
      to compare pressure-induced gastric accommodation in healthy volunteers (HV) and
      patients with functional dyspepsia (FD). MATERIAL AND METHODS: Ten HV, and 11 FD
      patients were examined twice; once in the fasting state and once postprandially.
      Intragastric bag pressure was raised from 1 to 12 mmHg in 4 min (ramp phase) and
      then kept constant for 5 min (tonic phase). RESULTS: Compared to HV, fasting FD
      patients had lower gastric accommodation rates (0.9+/-0.2 versus 2.5+/-0.4 ml/s,
      p=0.002), lower maximum volume (239+/-39 versus 428+/-64 ml, p=0.01) and a longer
      accommodation time (157+/-26 versus 92+/-15 s, p=0.03). A test meal prior to
      distension tended to normalize the response in FD patients. CONCLUSIONS: This new
      barostat paradigm allowed detailed analysis of short-term pressure-induced
      accommodation in man. Impaired gastric distension-induced accommodation is a
      novel abnormality in FD.

PMID- 16638697
TI  - Prevalence of celiac disease: before and after a national change in feeding
      recommendations.
AB  - OBJECTIVE: A national change in infant feeding recommendations was proposed in
      1996 in Sweden: a slow introduction to gluten during weaning was stressed, the
      recommendation being introduction at 4 instead of 6 months of age. The aim of the
      present study was to compare the prevalence of celiac disease in healthy young
      children born before and after the new feeding recommendations in 1996. MATERIAL
      AND METHODS: Sera from 679 children at a median age of 2.9 years (range 2.5-4.2
      years) born between January 1996 and November 1997 were investigated with IgA
      antigliadin antibodies (AGA) and IgA-endomysial autoantibodies (EMA) and compared
      with 690 age-matched children born between July 1992 and June 1993. Children with
      a positive test for EMA and AGA or EMA only were re-tested, and if positive at
      follow up, investigated with intestinal biopsy. RESULTS: At baseline, 2.2%
      (15/679) children were positive for EMA and another 0.6% (4/679) for both EMA and
      AGA. One child refused to be re-tested and eight children were still EMA positive
      at follow-up. Intestinal biopsy was performed in seven children (one declined
      biopsy), of whom three showed total villous atrophy. Two children with EMA titers
      1:640, respectively, refused further participation in the study, but were
      strongly suspected to have celiac disease. In total, 0.7% (5/679) (95% confidence
      interval (CI) = 0.1-1.4%) were considered to have celiac disease compared with
      1.3% (9/690) (95% CI = 0.4-2.2%) in the control group (p=0.4217). In addition,
      0.3% of the children were diagnosed with symptomatic celiac disease compared with
      0.7% in controls (p=0.0134). CONCLUSIONS: The prevalence of symptomatic celiac
      disease declined after the infant dietary recommendations were introduced in
      1996, but we could not find any difference in undiagnosed celiac disease between
      the screened children born before and those born after 1996.

PMID- 16638698
TI  - Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease.
AB  - OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are chronic
      inflammatory diseases of the bowel, the causes of which are not fully known.
      Ethnic differences in disease prevalence, familial aggregation of the disease and
      studies of twins provide the most important evidence to suggest that genetic
      factors play a role in the pathogenesis of inflammatory bowel disease (IBD). The
      aim of this study was to examine the allelic polymorphisms that can determine the
      immune response levels in tumor necrosis factor alpha (TNFalpha), interleukin
      1beta (IL-1B), interleukin-1 receptor antagonist ( IL-1RN) and interleukin-10 (IL
      10) genes and to investigate their roles in the inflammatory pathway in IBD.
      MATERIAL AND METHODS: The study included 120 patients with UC and 70 patients
      with CD who were diagnosed either endoscopically or histopathologically. The
      control group comprised 105 healthy individuals who stated that they had never
      had any bowel disease during their life span. The polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method for polymorphisms in
      the TNFalpha gene at positions -308 and -238, the IL-10 gene at positions -1082
      and -627, the IL-1B gene at -511 regions and the variable number of tandem repeat
      (VNTR) method for polymorphism in the intron 2 of the IL-1RN gene were performed.
      The results were analyzed on agarose gel electrophoresis. RESULTS: No significant
      differences were found in the allele and genotype frequencies of the
      polymorphisms in the IL-1B, IL10, TNFalpha and IL-1RN genes between the patients
      with UC and CD and controls. CONCLUSIONS: The results suggest that these
      polymorphisms were not important risk factors in the susceptibility to IBD in
      Turkish patients.

PMID- 16638700
TI  - Lack of association between appendectomy and primary biliary cirrhosis.
AB  - OBJECTIVE: In view of the possible implication of various environmental factors
      in the pathogenesis of primary biliary cirrhosis (PBC), the role of appendectomy
      in patients with PBC and other chronic liver diseases from Central Greece was
      investigated. MATERIAL AND METHODS: The medical files of 68 patients with PBC and
      gender- and age-matched controls with chronic hepatitis C virus (HCV) infection
      (n=65) and chronic hepatitis B virus (HBV) infection (n=67) were reviewed for the
      history and time of appendectomy. RESULTS: Nineteen of 68 (27.9%) PBC patients,
      32 of 65 (49.2%) patients with chronic HCV infection and 22 of 67 (32.8%)
      patients with chronic HBV infection had a history of appendectomy. There was a
      significant higher frequency of appendectomy in patients with chronic hepatitis C
      (p = 0.012, chi(2) test) compared to patients with PBC. There were no significant
      differences in the clinical and histological characteristics of PBC patients with
      or without a history of appendectomy. CONCLUSION: In this case-control study we
      were unable to provide evidence of an association between primary biliary
      cirrhosis and the occurrence of appendectomy.

PMID- 16638699
TI  - Obesity is the only independent factor associated with ultrasound-diagnosed non
      alcoholic fatty liver disease: a cross-sectional case-control study.
AB  - OBJECTIVE: There is increasing interest in ultrasound-diagnosed non-alcoholic
      fatty liver disease (NAFLD) in the ambulatory care setting. The aim of this study
      was to determine the clinical and metabolic features of ultrasound-diagnosed
      NAFLD. MATERIAL AND METHODS: Fifty ultrasound-diagnosed NAFLD patients who had
      not consumed alcohol for at least the previous 3 months were matched with 100
      controls by age and gender distribution. Clinical, biochemical, and nutritional
      variables were compared between the ultrasound-diagnosed NAFLD patients and the
      controls. Conditional logistic regression analyses were used to identify
      independent factors associated with ultrasound-diagnosed NAFLD. RESULTS: The
      ultrasound-diagnosed NAFLD patients had higher values on the anthropometric
      measurements than those of the controls. Aspartate aminotransferase (ASAT),
      alanine aminotransferase (ALAT), uric acid, and gamma-glutamyl transpeptidase
      levels were higher in the ultrasound-diagnosed NAFLD patients than those in the
      controls (p<0.001). The ASAT/ALAT ratio of the ultrasound-diagnosed NAFLD
      patients was lower than that of the controls (p<0.001). Total cholesterol,
      triglycerides, high-density lipoprotein (HDL)-cholesterol, non-HDL-cholesterol,
      atherogenic index, fasting glucose, systolic blood pressure (BP), diastolic BP,
      and pulse pressure were higher in the ultrasound-diagnosed NAFLD patients than in
      the control subjects, while lipoprotein(a) was lower. There were no significant
      differences in low-density lipoprotein (LDL)-cholesterol levels or nutritional
      intake between patients and controls. Abnormal ASAT or ALAT,
      hypertriglyceridemia, lower HDL-cholesterol levels, silent myocardial ischemic
      pattern on electrocardiogram (ECG), impaired fasting glucose, and obesity were
      common among the ultrasound-diagnosed NAFLD patients. The only independent factor
      associated with ultrasound-diagnosed NAFLD was obesity (p<0.001). CONCLUSIONS:
      Our data suggest that NAFLD diagnosed by ultrasound is associated with
      hypertriglyceridemia, impaired fasting glucose, silent myocardial ischemic
      pattern of ECG, obesity, and abnormal liver tests in adults. Among these factors,
      obesity was the only independent factor associated with ultrasound-diagnosed
      NAFLD.

PMID- 16638701
TI  - Health-related quality of life before, during and after combination therapy with
      interferon and ribavirin in unselected Swedish patients with chronic hepatitis C.
AB  - OBJECTIVE: To study the relationship between health-related quality of life
      (HRQOL) and mode of acquisition, treatment discontinuations, drop in haemoglobin
      levels and treatment outcome in patients with chronic hepatitis C (CHC). MATERIAL
      AND METHODS: Consecutive unselected Swedish patients with CHC completed the SF-36
      questionnaire before, during and after treatment with interferon and ribavirin.
      Results. At baseline, HRQOL was reduced in all SF-36 subscales in our patients
      (n=147) as compared with the general Swedish population. Former intravenous drug
      users (IVDUs) scored significantly lower in social function (p=0.03) and mental
      health (p=0.03) than patients who had acquired their infection from blood
      transfusions (PTH). A decline of >40 points in HRQOL from baseline to week 12 was
      noticed in the role limitations-physical (RP) score for the IVDU and PTH groups
      (p<0.0001 and 0.001, respectively). Patients with a >or=20% fall in haemoglobin
      levels at treatment week 12 had a significantly poorer RP (p=0.006) and role
      limitations-emotional score (p<0.02) than patients with a <10% fall. Early
      treatment dropouts had significantly lower HRQOL scores at baseline than adherent
      patients. At follow-up, sustained viral responders had significantly higher
      scores than non-responders. CONCLUSIONS: Swedish outpatients with CHC have a
      marked reduction in their HRQOL as compared to the general population. Therapy
      reduces HRQOL most substantially in those with a marked reduction in haemoglobin.
      Early dropouts from therapy have significantly lower HRQOL scores at baseline
      than adherent patients, and sustained viral responders improve their HRQOL
      significantly more than non-responders.

PMID- 16638702
TI  - No major effect of the CD28/CTLA4/ICOS gene region on susceptibility to primary
      sclerosing cholangitis.
AB  - OBJECTIVE: Primary sclerosing cholangitis (PSC) is currently thought to be an
      immune-mediated disease, where both host genes and environmental factors
      interact. Some of the immunoregulatory genes responsible for individual
      susceptibility to PSC have been identified. The co-stimulatory receptor gene
      cluster on chromosome 2q33 encodes both the positive T-cell regulators CD28 and
      ICOS, and the negative regulator CTLA4. The CTLA4 gene has been implicated in
      several immune-mediated diseases, but it is not known whether PSC is associated
      with any of these genes. MATERIAL AND METHODS: Polymerase chain reaction (PCR)
      based genotyping was performed on 144 PSC patients and 285 controls. Two single
      nucleotide polymorphisms (SNPs) in the CTLA4 gene were investigated as well as
      six microsatellites covering approximately 262 kb of the flanking regions,
      including the ICOS and CD28 genes. RESULTS: Overall, there were no statistically
      significant differences between PSC patients and controls in genotype and allele
      frequencies for the CTLA4 +49AG and CT60 SNPs or for the CD28-A, CD28-B, SARA43,
      SARA1, SARA31, and SARA47 microsatellite markers. Nor were any associations with
      clinical subgroups observed. CONCLUSIONS: There are no major effects of the
      CD28/CTLA4/ICOS gene region on susceptibility to PSC, but minor contributions (OR
      <1.8) cannot be excluded.

PMID- 16638703
TI  - Liver TX for hepatitis C cirrhosis in a low prevalence population: risk factors
      and status at evaluation.
AB  - OBJECTIVE: Hepatitis C virus (HCV) cirrhosis is the most common indication for
      liver transplantation (LTX) world-wide. The prevalence of HCV infections is much
      lower in Norway than in most other countries from which data on HCV infection and
      liver transplantation have been published. MATERIAL AND METHODS: Patients with
      HCV infection referred for evaluation of a possible LTX between 1990 and 2005
      were included in the study. Their clinical status, biochemical parameters and
      risk factors were recorded. All patients were followed until 1 January 2005
      irrespective of transplantation status. RESULTS: Fifty-one patients were
      included; 80% were males and 18% were non-Caucasians. Previous intravenous drug
      abuse (28%) and exposure to contaminated IgG products (15%) were the most common
      routes of infection. In 45/51 (88%) of the evaluated patients at least one risk
      factor for rapid progression of HCV disease was identified. Twenty-seven patients
      were accepted on the waiting list. The MELD (model for endstage liver disease)
      score for the accepted patients was significantly higher than that for the
      patients who were not listed because they were found to be too healthy (18.4
      versus 12.1, p<0.01). Twenty-four patients (89% of those listed) received a liver
      allograft; their 1-, 3- and 5-year survival rates following LTX were 81%, 68% and
      68%, respectively. Two patients needed a second transplantation. CONCLUSIONS: A
      low number of HCV-infected patients have so far been evaluated for LTX in Norway.
      The present study demonstrates that almost all of the HCV patients progressing to
      cirrhosis and being evaluated for LTX in Norway have additional risk factors for
      development of cirrhosis.

PMID- 16638704
TI  - Endobiliary brush biopsy: Intra- and interobserver variation in cytological
      evaluation of brushings from bile duct strictures.
AB  - OBJECTIVE: Obtaining cytological specimens by wire-guided endobiliary brushing at
      the time of endoscopic retrograde cholangiopancreatography (ERCP) is a convenient
      way to reach a diagnosis. Sensitivity for malignant disease is generally around
      50% and specificity around 100%. The present study was designed to assess the
      reproducibility of the cytological examination. MATERIAL AND METHODS: Samples
      were obtained from 55 consecutive patients with biliary duct strictures that
      eventually turned out to be caused by malignant disease in 41 patients (73%). The
      cytology specimens were evaluated twice in different random order with an
      interval of at least 4 months by two pathologists blinded to the final diagnoses.
      Suitability for diagnosis (suitable, suboptimal or unsuitable) and cytologic
      diagnosis (benign, atypical, suspicious for malignancy and malignant cells) were
      registered. Kappa analysis was applied. RESULTS: Regarding suitability for
      diagnosis, the two observers reproduced their findings in 84% (kappa 0.76) and
      87% (0.59) (p>0.05), while the interobserver variations on the two occasions were
      76% and 78% (kappa 0.49 and 0.58, respectively) (p>0.05). Five percent of samples
      were rated as inadequate for diagnosis in at least one reading; 18% were
      suboptimal and 62-82% were suitable. The observers reproduced their cytological
      diagnosis in 77% and 71% (weighted kappa 0.83 and 0.75) (p>0.05), and agreed on
      the cytological diagnosis in 65% and 73% (weighted kappa 0.65 and 0.75) (p>0.05).
      CONCLUSIONS: The intra- and interobserver agreement in cytological evaluation of
      endobiliary brushings from bile duct strictures is generally good. The rates of
      inadequate and suboptimal samples can probably be reduced by modifications of the
      brush design.

PMID- 16638705
TI  - Potential mechanisms and significance of acute pancreatitis-associated liver
      injury.

PMID- 16638706
TI  - Capsule endoscopy in clinical routine in patients with suspected disease of the
      small intestine: a 2-year prospective study.
AB  - OBJECTIVE: Capsule endoscopy is a promising method for examining the small
      intestine. The study was performed to evaluate the use of capsule endoscopy in
      clinical routine in patients with suspected disease of the small intestine.
      MATERIAL AND METHODS: Consecutive patients with clinically suspected disease of
      the small intestine referred for capsule endoscopy between 1 January 2003 and 31
      December 2004 were included in the study. All patients had previously completed a
      conventional diagnostic work-up with upper and lower endoscopy as well as
      abdominal CT scan or small-bowel enteroclysis. RESULTS: A total of 167 patients
      were referred during the time period and 195 procedures were performed. Seventeen
      (8.7%) of the procedures were unsuccessful, with no visualization of the small
      bowel. In the remaining procedures the caecum was reached in 83%. The reason for
      referral was gastrointestinal bleeding (30%), iron-deficiency anaemia (25%),
      abdominal pain (15%), diarrhoea (13%) and Crohn's disease (12%). Pathology was
      found in 27% of the patients, with the highest diagnostic yield in patients
      referred for Crohn's disease (60%) and the lowest yield (4%) in patients referred
      for abdominal pain. There were no complications, with the exception of one
      patient referred for Crohn's disease who had transient abdominal pain during the
      procedure. CONCLUSIONS: Capsule endoscopy is a safe and well-tolerated procedure.
      In unselected patients with clinically suspected disease of the small intestine,
      the procedure gives additional information to conventional diagnostic procedures
      in 27% of patients. Incomplete examination of the small intestine was frequent in
      our group of patients.

PMID- 16638707
TI  - Portosystemic myelopathy: spastic paraparesis after portosystemic shunting.
AB  - Portosystemic encephalopathy (PSE) is a well-known, common complication of portal
      hypertension. It is thought to be caused by nitrogenous substances such as
      ammonia, which are normally cleared from the blood stream by the liver. In
      cirrhosis and other hepatic disorders with portosystemic shunting (PSS)-- either
      surgical portosystemic anastomoses (PSA) or spontaneous PSS-- the collateral
      vessels bypass the liver allowing the accumulation of toxic, ammoniacal
      substances in the blood and tissues. PSE is characterized by encephalopathy;
      portosystemic myelopathy (PSM) is characterized by paresis of the extremities,
      Babinski signs and muscle spasticity in patients with cirrhosis and/or PSS.
      Usually only the lower extremities are involved. This report presents the first
      case of this syndrome observed 5 years after a transjugular intrahepatic
      portosystemic shunt. The 31 year old man with chronic Hepatitis B developed
      complete spastic paraparesis within 4 weeks after onset of clinical/neurological
      symptoms, accompanied by an episode of severe hepatic encephalopathy. The
      transcortical magnetic stimulation showed normal motoric stimulation times to the
      abductor digiti minimi muscles but no stimulation to the tibialis muscles was
      seen. Lumbar stimulation to the tibialis muscles, however, was normal. This
      indicates loss of motor neurons in the spinal cord, a characteristic finding in
      patients with portosystemic myelopathy. We performed a search of the literature
      for all reported cases of cirrhosis and/or PSS that developed PSM. However, the
      intervals between the construction of a shunt and the diagnosis of portosystemic
      myelopathy were shorter in total portacaval shunts (median 16 months) than in
      partial, non-portacaval shunts (median 60 months, p < 0.01). This suggests that
      not only the shunt itself but also the shunted volume contributes to the
      development of the syndrome Sixty-one patients with PSM have been reported in the
      literature since 1944. PSE had developed before PSM in almost all cases. PSM
      occurred from 1 month to 10 years after the creation of portacaval anastomoses
      (PCA) or splenorenal shunts (SRS) or in cirrhotic patients without shunts. No one
      type of liver disease or type of shunt appears to predispose to PSM. The
      mechanisms of PSE and PSM are thought to be similar and of nitrogenous origin,
      but their pathogenesis remains unknown. Lathyrism, a toxic syndrome with similar
      symptoms and signs, is caused by the ingestion of a legume, Lathyrus sativa,
      which contains beta-N-oxalo-L amino-L-alanine (BOAA). This animal model with or
      without BOAA appears to offer a reliable way of studying PSM experimentally.

PMID- 16638708
TI  - Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and
      pheochromocytoma in patients with Carney triad and neurofibromatosis type 1.
AB  - There is rapid evolution in the functional imaging of tumours. In two patients
      with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST),
      previously unrecognized tumours were visualized by combined 2-tracer positron
      emission tomography (PET), which also provided precise information about tumour
      type. PET imaging led to radical resection and the diagnoses were
      histopathologically confirmed. GISTs from the Carney patient and the patient with
      neurofibromatosis type 1 (NF1) both lacked KIT mutations.

PMID- 16638709
TI  - Rosuvastatin: a safe and effective treatment for dyslipidaemia associated with
      non-alcoholic steatohepatitis (NASH).

PMID- 16638711
TI  - In utero and neonatal sensitivity of ApcMin/+ mice to radiation-induced
      intestinal neoplasia.
AB  - PURPOSE: To assess the sensitivity of ApcMin/+ mice (adenomatous polyposis coli
      Apc, multiple intestinal neoplasia, Min) to the development of intestinal
      adenomas after x-irradiation in utero, as neonates, or as young adults. MATERIALS
      AND METHODS: CHB6 ApcMin/+ mice were exposed to an acute dose of 2 Gy x-rays
      either in utero on day 7 or 14 post-conception, as 2-day or 10-day neonates or as
      35-day young adults. Tumour identification and counting was performed 200-214
      days later. RESULTS: Irradiation as 10-day-old neonates resulted in a
      significantly greater overall tumour incidence (average of about 130 tumours per
      animal) than irradiation as 35-day-old young adults (about 70 tumours).
      Irradiation as 2-day-old neonates resulted in an intermediate incidence (about 85
      tumours). In contrast, the greatest tumour incidence observed after in utero
      irradiation of ApcMin/+ mice, of about 44 tumours per animal after 2 Gy
      irradiation at 14 days post-conception, was significantly lower than the
      incidence in irradiated adults. Tumour incidences after irradiation as 7-day
      embryos was not significantly raised above numbers in unirradiated controls
      (about 30 tumours). These tumour numbers include cystic crypts, largely radiation
      induced, which were classed as early stage microadenomas on the basis of loss of
      wild-type Apc+ and expression of beta-catenin. CONCLUSIONS: The sensitivity of
      ApcMin/+ mice to the induction of intestinal tumours by radiation was shown to be
      in the order: 10 d neonates>2 d neonates>35 d young adults>14 d fetus>7 d embryo.

PMID- 16638712
TI  - A pilot study examining germline minisatellite mutations in the offspring of
      Danish childhood and adolescent cancer survivors treated with radiotherapy.
AB  - PURPOSE: To investigate germline mutation rate at eight minisatellite loci in 24
      Danish families, where one parent is the survivor of childhood or adolescent
      cancer treated with radiotherapy. MATERIALS AND METHODS: Parents and offspring
      were profiled for eight hypervariable minisatellite loci (B6.7, CEB1, CEB15,
      CEB25, CEB36, MS1, MS31, MS32) by Southern blotting. RESULTS: Seven paternal
      mutations were observed for 130 informative alleles in 18 offspring from 11
      radiation-exposed fathers (mean preconceptional dose for offspring 0.29 Gy,
      range<0.01-1.2 Gy), compared to six mutations for 146 informative alleles in 21
      offspring from 13 unexposed fathers. No statistically significant difference
      between the total paternal mutation rates was observed (5.4% for exposed fathers
      and 4.1% for unexposed fathers). Three maternal mutations were observed for 148
      informative alleles in 21 offspring from 13 radiation-exposed mothers (mean
      preconceptional dose for offspring 0.71 Gy, range <0.01-9.2 Gy), compared to one
      mutation for 130 informative alleles in 18 offspring from 11 unexposed mothers.
      Again, no statistically significant difference was observed between the total
      maternal mutation rates (2.0% for exposed mothers and 0.8% for unexposed
      mothers). CONCLUSIONS: The data from this pilot study demonstrate no
      statistically significant increase in germline minisatellite mutation rate
      associated with radiotherapy for childhood and adolescent cancer.

PMID- 16638713
TI  - The NK1.1+T cells alive in irradiated mice play an important role in a Th1/Th2
      balance.
AB  - PURPOSE: Ionizing radiation is known to reduce the helper T (Th) 1 like function,
      resulting in a Th1/Th2 imbalance. We studied whether NK1.1+T cells which were the
      most resistant against gamma-irradiation impact on the imbalanced immune response
      after irradiation. MATERIALS AND METHODS: C57BL/6 mice received a whole-body
      gamma-irradiation (WBI) of 4 Gy. The primary T cells were separated by magnetic
      cell sorter (MACS) using the anti-CD90.2 antibody. The apoptotic cells were
      detected by propidium iodide (PI) staining. To determine the Th1 and Th2 cell
      functions, the production of interferon (IFN)-gamma and interleukin (IL)-4 were
      analysed by a reverse transcriptase-polymerase chain reaction (RT-PCR) and an
      enzyme linked immunosorbent assay (ELISA). NK1.1+T cells were detected by flow
      cytometry. For depletion of the NK1.1+T cells in the WBI mice, anti-asialo GM1
      antiserum was injected. RESULTS: The CD90.2 positive cells of the WBI mice
      produced significantly more Th2 type cytokines and also produced Th1 type
      cytokines at a not lower level than normal mice, and contained a higher absolute
      number of NK1.1+T cells. Also, the proportion of the NK1.1+T cells increased in
      the WBI mice. We found that the NK1.1+T cells were resistant to radiation-induced
      apoptosis in comparison with the conventional T cells. The depletion of NK1.1+T
      cells in WBI mice resulted in higher production of IgE and IL-4 and lower
      secretion of IL-12p70. CONCLUSION: Our findings revealed that NK1.1+T cells that
      survive at an early stage after irradiation play an important role in the balance
      of the immune responses at a late stage after irradiation.

PMID- 16638714
TI  - Peripheral leukocyte response to oncological radiotherapy: expression of heat
      shock proteins.
AB  - PURPOSE: To study Heat Shock Proteins (HSP) expression in patients subjected to
      radiotherapy and their potential use as biomarkers for radiation tolerance. An
      evaluation is also made of whether irradiated volume is critical to the outcome
      of normal tissue injury using polymorphonuclear neutrophils as biosensors, and
      whether HSP antibodies (Ab) may be involved in post-radiotherapy disease.
      MATERIAL AND METHODS: Twelve patients receiving the same total dose of
      radiotherapy, but in three different volumes, and four healthy volunteers used as
      controls were analysed. hsp27 and 70i mRNA were determined by Reverse
      Transcription-Polymerase Chain Reaction (RT-PCR) and Southern-blot, HSP by flow
      cytometry, and HSP-Ab by Enzyme-linked Immnoadsorbent Assay (ELISA). The clinical
      protocol included radiation related toxicity based on clinical and analytical
      scales. RESULTS: Radiotherapy caused hsp downregulation, maximum in patients with
      the largest irradiated volumes, and a decrease in intracellular HSP content.
      Patients with greatest intraleukocyte HSP levels before treatment suffered more
      severe radiation morbidity. Patients with endocrine neoplasms presented the
      highest HSP-Ab titers. CONCLUSIONS: Radiotherapy downregulates hsp27 and 70i,
      which would enhance radiosensitivity. HSP content prior to treatment is suggested
      as a prognostic biomarker for radiation tolerance, with circulating leukocytes as
      biosensors. HSP-Ab may be biomarkers of tumor disease, but do not seem to be
      involved in the morbidity of acute post-radiotherapy disease, which is closely
      related to the volumes irradiated.

PMID- 16638715
TI  - Identification of differentially transcribed genes in human lymphoblastoid cells
      irradiated with 0.5 Gy of gamma-ray and the involvement of low dose radiation
      inducible CHD6 gene in cell proliferation and radiosensitivity.
AB  - PURPOSE: To identify candidate genes specifically involved in response to low
      dose irradiation in human lymphoblastoid cells; to better clarify the role of the
      human chromodomain helicase DNA binding protein 6 gene (CHD6), one of these
      genes, in cell proliferation and radiosensitivity. MATERIALS AND METHODS: DNA
      microarray technology was used to analyse global transcriptional profile in human
      lymphoblastoid AHH-1 cells at 4 h after exposure to 0.5 Gy of gamma-ray. Gene
      expression changes were confirmed by semi-quantitative reverse transcription-
      polymerase chain reaction (RT-PCR) and Northern blot. RNA interfering technology
      was employed to knock-down the CHD6 gene in A549 cells. Colony-forming ability
      was used to analyse radiosensitivity. RESULTS: The microarray assay revealed a
      set of 0.5 Gy-responsive genes, including 30 up-regulated genes and 45 down
      regulated genes. The up-regulated genes include a number of genes involved in:
      signal transduction pathways, e.g., STAT3, CAMKK2, SIRT1, CREM, MAPK3K7IP2 and
      GPR56; transcription or DNA-binding, e.g., CHD6, CRSP3, SNURF, SH2 domain binding
      protein 1 and MIZF. Some of the down-regulated genes are involved in:
      cytoskeleton and cell movement (WASF2, LCP1, MSN, NIPSNAP1, KIF2C); DNA
      replication and repair (MCM2, MCM3, MCM7 and XRCC-4). Radiation-increased
      expression of CHD6 was also found in A549 cells and HeLa cells. The sustained
      CHD6 induction was restricted to relatively low doses (0.2 Gy or 0.5 Gy), no
      change occurring after 4 Gy irradiation. Silencing of CHD6 mediated by siRNA
      increased the growth rate of A549 cells by 40 approximately 60%. Most
      importantly, silencing CHD6 led to an increased radioresistance of A459 cells to
      radiation doses up to 2 Gy, but barely affected the sensitivity of cells at 4 and
      8 Gy. CONCLUSION: This study has identified a set of genes responsive to 0.5 Gy
      of gamma-rays. CDH6 gene can be specifically up-regulated by low dose
      irradiation, and its inducible expression could be involved in a low dose
      hypersensitive response.

PMID- 16638716
TI  - Differential effects of CLDR and PDR brachytherapy on cell cycle progression in a
      syngeneic rat prostate tumour model.
AB  - PURPOSE: The study consisted of two treatment arms comparing the effects of CLDR
      (continuous low dose rate) and PDR (pulsed dose rate) brachytherapy on cell cycle
      progression in a radioresistant rat prostate tumour model. MATERIALS AND METHODS:
      Interstitial PDR and CLDR brachytherapy (both 192-Ir, 0.75 Gy/h) were
      administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously
      into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to
      40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell
      subpopulations were determined at 4 h (3 Gy), 24 h (18 Gy), 48 h (20 and 36 Gy),
      as well as during the subsequent redistribution period (20 and 40 Gy) at 72, 96,
      and 120 h. Tumours either implemented with an empty tubing system (n=5) or under
      undisturbed growth (n=5) served as controls. Three animals were irradiated per
      time point and exposure condition. At least two flow cytometrical analyses were
      carried out per animal. RESULTS: The aneuploid cells possessed a constant DNA
      Index of 1.9+/-0.06. In contrast to sham-treated controls, the aneuploid cell
      fraction with G2/M DNA content was significantly increased (p<0.05) after
      initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an
      earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p<0.05)
      with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but
      then more pronounced cell cycle changes, particularly expressed during the
      redistribution period after both 20 and 40 Gy. CONCLUSION: CLDR and PDR
      brachytherapy showed differential effects on cell cycle progression. The
      induction of a significantly earlier but also less persistent G2/M cell cycle
      arrest after CLDR compared to PDR brachytherapy implies that a substantially
      higher fraction of tumour cells are irradiated in G2/M after CLDR.

PMID- 16638717
TI  - Treatment of mice with stem bark extract of Aphanamixis polystachya reduces
      radiation-induced chromosome damage.
AB  - PURPOSE: Normal tissue radiosensitivity is the major limiting factor in
      radiotherapy of cancer. The use of phytochemicals may reduce the adverse effects
      of radiation in normal tissue. The effect of ethyl acetate fraction of
      Aphanamixis polystachya (EAP) was investigated on the radiation-induced
      chromosome damage in the bone marrow cells of Swiss albino mice exposed to
      various doses of gamma-radiation. MATERIALS AND METHODS: The mice were divided
      into two groups, one group was exposed to 0, 1, 2, 3, 4 or 5 Gy of gamma
      radiation, while another group received 7.5 mg/kg body weight (BW) of EAP 1 h
      before exposure to 0, 1, 2, 3, 4 or 5 Gy of gamma-radiation. Various asymmetrical
      chromosome aberrations were studied in the bone marrow cells of mice at 12, 24 or
      48 h post-irradiation. To understand the mechanism of action of the free radical
      scavenging activity of 0, 5, 10, 20, 30, 40, 50, 60 or 70 microg/ml EAP, assays
      were carried out in vitro. RESULTS: Irradiation of mice to different doses of
      gamma radiation caused a dose dependent elevation in the frequency of aberrant
      cells and chromosome aberrations like chromatid breaks, chromosome breaks,
      dicentrics, acentric fragments and total aberrations at all the post-irradiation
      times studied. The maximum asymmetrical aberrations were scored at 24 h post
      irradiation except chromatid breaks that were highest at 12 h post-irradiation. A
      maximum number of polyploid and severely damaged cells (SDC) were recorded at 24
      h post-irradiation in the SPS+irradiation group. Treatment of mice with 7.5 mg/kg
      BW of EAP before exposure to 1-5 Gy of whole body gamma-radiation significantly
      reduced the frequencies of aberrant cells and chromosomal aberrations like
      acentric fragments, chromatid and chromosome breaks, centric rings, dicentrics
      and total aberrations at all post-irradiation scoring times (p<0.01). The EAP
      showed a concentration dependent scavenging of hydroxyl, superoxide, 2,2'
      diphenyl-1-picryl hydrazyl (DPPH) radicals and the 2,2-azino-bis-3-ethyl
      benzothiazoline-6-sulphonic acid (ABTS) cation radicals in vitro. EAP treatment
      also reduced lipid peroxidation in bone marrow cells in a concentration dependent
      manner. CONCLUSION: Our study demonstrates that EAP protects mouse bone marrow
      cells against radiation-induced chromosomal aberrations and this reduction in
      radiation-induced chromosome damage may be due to free radical scavenging and
      reduction in lipid peroxidation. The radioprotection by EAP is best comparable to
      that of protection demonstrated by the grape fruit flavonone, naringin, in our
      earlier studies in mouse bone marrow cells.

PMID- 16638718
TI  - Combined electron emission effects on the biologically damaging efficiency of
      125I.
AB  - PURPOSE: One important obstacle in modeling the biological damage of 125I lies in
      the collective effects of the emitted electrons. The huge number of possible
      different ways of atomic rearrangement causes a strong variability in the number
      and energies of the emitted electrons. The aim of this work is to tabulate,
      separately for each atomic rearrangement pathway, the absorbed doses and the
      single-strand breaks (SSB) probabilities for different size nanospheres of liquid
      water. METHODS: A simple deterministic (non-stochastic) atomic rearrangement
      model of only 265 pathways is appropriate for modeling the electron-capture and
      internal conversion processes in 125I. The feasibility of the atomic
      rearrangement model is verified by comparing the SSB yield for ultrasoft X-ray
      sources with Lobachevsky's experimental data. RESULTS: A linear equation is
      sufficient for describing the SSB probability as a function of the dose absorbed
      in a small volume surrounding the labelled nucleotide 125I-dC. CONCLUSIONS: The
      application of a deterministic atomic rearrangement model to Auger electron
      emission spectra gives a new perspective to the study of low linear energy
      transfer (LET) radiation effects on DNA. The damages induced by point electron
      capture (EC) sources and by macroscopic X-ray sources are compared.

PMID- 16638722
TI  - Incidentalomas of the parathyroid gland: multiple presentations, variable
      function, and review of the literature.
AB  - OBJECTIVE: To present a series of cases of parathyroid incidentalomas and review
      the related medical literature. METHODS: The medical records of all patients of
      one surgeon who underwent unplanned removal of enlarged parathyroid glands found
      either during a surgical procedure performed for indications other than
      hyperparathyroidism or by ultrasonography of the thyroid gland between September
      1989 and December 2003 were reviewed retrospectively. Clinical and laboratory
      data-- especially serum calcium and parathyroid hormone (PTH) levels--as well as
      information on postoperative parathyroid function are reported. RESULTS: Among
      421 patients (355 who underwent thyroidectomy and 66 who underwent transhiatal
      esophagectomy), 5 cases of parathyroid incidentalomas (1.2%) were identified.
      These incidental parathyroid adenomas were found during thyroidectomy for thyroid
      cancer in two patients, during esophagectomy for esophageal cancer in one patient
      (the first such reported case), and during ultrasonography of the neck for
      evaluation of thyroid nodules in two patients. Of the five patients, three had a
      normal and one had a slightly increased serum calcium concentration
      preoperatively; the serum calcium level was not determined preoperatively in the
      other patient. In one patient in whom intraoperative PTH level was determined
      both before and after resection of a large parathyroid adenoma, the initially
      high PTH value (180 pg/mL) declined to the normal range (48.2 pg/mL). In another
      patient, bone densitometry 9 months postoperatively showed an 8% increase in T
      score for the lumbar spine and a 3.9% increase in T-score at the femoral neck, in
      comparison with bone density tests done 3 months preoperatively. No patient had
      persistent or recurrent hyperparathyroidism or hypoparathyroidism postoperatively
      or during subsequent follow-up. CONCLUSION: Incidental identification of enlarged
      parathyroid glands during a neck surgical procedure is not common but does occur.
      Intraoperative and postoperative measurements of serum calcium and PTH along with
      postoperative bone density testing can help determine whether such parathyroid
      incidentalomas are functional. These enlarged parathyroid glands should be
      removed.

PMID- 16638723
TI  - Evaluation and treatment of osteoporosis in patients with a fragility hip
      fracture.
AB  - OBJECTIVE: To determine whether patients with fragility hip fractures underwent
      assessment and treatment of osteoporosis during initial hospitalization or
      recommendations for such intervention were made to the primary care provider
      (PCP) at the time of hospital dismissal. METHODS: A review of medical records of
      patients admitted with a low-impact hip fracture to the Royal University Hospital
      in Saskatoon, Saskatchewan, Canada, was performed to determine whether
      recommendations were made to evaluate for or treat osteoporosis. In addition, a
      questionnaire was sent to the orthopedic surgeons practicing at the hospital to
      help identify barriers to widespread diagnosis and treatment of osteoporosis in
      such patients. RESULTS: Between January and December 2004, 174 patients with
      fragility hip fractures were admitted to the Royal University Hospital. The mean
      age of these patients was 82.5 +/- 9.8 years. Evaluation for treatment of
      osteoporosis was recommended in only 9 patients (5%). We found no significant
      differences in the intervention rates between male and female patients, between
      patients with and those without a prior history of osteoporosis or fracture,
      between patients who were previously taking osteoporosis medications and those
      who were not, and between patients who were seen by a medical consultant and
      those who were not. Most orthopedic surgeons believed that they were primarily
      responsible for the surgical care of these patients, and because they did not see
      these patients in regular follow-up, the management of osteoporosis was
      considered the responsibility of the PCP. CONCLUSION: The results of this study
      indicate that only a small number of patients with fragility hip fractures
      receive appropriate evaluation or treatment for underlying osteoporosis either
      during initial hospitalization or at the time of dismissal from the hospital. In
      this study, most orthopedic surgeons believed that evaluation and treatment of
      osteoporosis were the responsibility of the PCP. Because these patients have an
      increased risk for future fractures, barriers to the diagnosis and treatment of
      osteoporosis need to be removed, and health-care professionals need to be
      educated about appropriate risk factor modification in these patients.

PMID- 16638724
TI  - Ganglioneuroma manifesting as an incidental adrenal mass in an adult with
      Turner's syndrome.
AB  - OBJECTIVE: To report a case of ganglioneuroma masquerading as an incidental
      adrenal mass in an adult patient with Turner's syndrome. METHODS: We present the
      clinical, laboratory, radiologic, and pathologic findings in this patient.
      RESULTS: A 31-year-old woman with Turner's syndrome who had previously been
      treated with growth hormone replacement had an incidentally discovered mass,
      apparently arising from the left adrenal gland. The mass was "silent" clinically
      and biochemically, but imaging characteristics were not reassuring for a benign
      cortical adenoma. Because of uncertainty regarding the nature of the mass, it was
      removed laparoscopically; during this procedure, it was noted to be intimately
      associated with, but anatomically distinct from, the left adrenal gland. The
      pathology report confirmed the presence of a benign ganglioneuroma. CONCLUSION:
      Although ganglioneuroma has previously been noted to be associated with Turner's
      syndrome (especially in pediatric patients), to the best of our knowledge this is
      the first report of a ganglioneuroma manifesting as an incidental adrenal mass in
      an adult patient with Turner's syndrome.

PMID- 16638725
TI  - Bowel perforation as a presenting feature of pheochromocytoma: case report and
      literature review.
AB  - OBJECTIVE: To report a case of colonic perforation as the initial manifestation
      of pheochromocytoma and discuss the underlying pathophysiologic mechanism.
      METHODS: The clinical, biochemical, radiologic, and pathologic findings are
      described. In addition, the management of the patient is discussed and the
      relevant literature reviewed. RESULTS: A 57-year-old man presented with large
      bowel perforation after pseudo-obstruction. Emergency laparotomy revealed two
      cecal perforations but no obstructing lesion; however, hypertension persisting
      postoperatively raised the suspicion of pheochromocytoma. This diagnosis was
      confirmed by measurement of 24-hour urinary hydroxymethylmandelic acid excretion
      and computed tomography of the abdomen. The tumor was subsequently resected
      without complication or recurrence of bowel symptoms. The pathophysiology of
      bowel perforation in patients with pheochromocytoma is not entirely clear but
      most likely involves bowel ischemia and necrosis as a result of mesenteric
      vasoconstriction. This setting coupled with increased intraluminal pressure as a
      consequence of pseudo-obstruction may cause perforation. CONCLUSION: Bowel
      perforation in patients with pheochromocytoma is rare and thought to be a
      consequence of intestinal ischemia and altered motility. This is potentially a
      life-threatening complication, particularly if the tumor remains undiagnosed and
      an emergency surgical procedure is necessary. Pharmacologic treatment of
      pheochromocytoma during pseudo-obstruction may prevent subsequent perforation.
      Clinicians should be aware of the potential gastrointestinal presentation of this
      tumor.

PMID- 16638726
TI  - Atypical cystic adenoma of the parathyroid gland: case report and review of
      literature.
AB  - OBJECTIVE: To describe the clinical course of a patient with atypical cystic
      parathyroid adenoma manifesting as hypercalcemic parathyroid crisis. METHODS: We
      present a case report and review the relevant literature on parathyroid cysts and
      atypical cystic parathyroid adenomas. RESULTS: A 76-year-old woman was evaluated
      for weakness, weight loss, urinary incontinence, and memory disturbances. She had
      severe hypercalcemia (calcium level, 18.3 mg/dL) in conjunction with an elevated
      parathyroid hormone level of 1,472 pg/mL. She received aggressive hydration,
      pamidronate, and calcitonin. Ultrasonography revealed a large cystic structure
      (5.8 cm) at the lower pole of the left thyroid lobe. She underwent surgical
      exploration of the neck, total thyroidectomy for multinodular disease of the
      thyroid, and subtotal parathyroidectomy. Intraoperatively, 25 mL of fluid was
      aspirated from the cystic mass, and the parathyroid hormone level in the fluid
      was 7,400,000 pg/mL. The final pathologic diagnosis was an atypical cystic
      parathyroid adenoma. CONCLUSION: Parathyroid cysts are uncommon and should be
      considered in the differential diagnosis of a neck mass. Although most
      parathyroid cysts are nonfunctional, 10% to 15% of such cysts are functional and
      can rarely manifest as acute parathyroid crisis. Atypical cystic parathyroid
      adenomas are rare and have an unpredictable clinical course. They exhibit some
      features of carcinoma but lack the indisputable evidence of malignant disease,
      such as angioinvasion or metastatic involvement. Treatment options for
      parathyroid cysts include aspiration, injection of sclerosing agents, and
      surgical excision.

PMID- 16638727
TI  - Unmasking of type III hyperlipoproteinemia by hypothyroidism: a dramatic
      illustration of altered lipoprotein metabolism in a postpartum woman.
AB  - OBJECTIVE: To illustrate the potential abnormalities in lipoprotein metabolism
      associated with type III hyper-lipoproteinemia and the modulation of their
      clinical expression by thyroid hormone and estrogenic status. METHODS: An
      illustrative case, with associated clinical and laboratory data, is presented,
      and relevant clinical and pathophysiologic studies from the literature are
      reviewed. RESULTS: A 35-year-old woman, at 7 months after delivery of her first
      child, presented to her family physician with a complaint of painful eruptions on
      the palms of her hands. On evaluation, she was found to have new hypothyroidism
      and severe hypertriglyceridemia (>1,569 mg/dL). Thyroxine replacement was
      initiated, and she was referred to the lipid clinic. When seen in the lipid
      clinic shortly thereafter, her triglyceride level had normalized, but her low
      density lipoprotein (LDL) fraction was strikingly elevated (representing a
      combination of elevated intermediate-density lipoprotein and LDL cholesterol). On
      physical examination, palmar xanthomas were noted, suggestive of type III
      hyperlipoproteinemia. This diagnosis was further supported by homozygosity at the
      apolipoprotein E (apo E) gene locus for the apo E2 allele implicated in this
      condition. Ultimately, with attainment of euthyroidism in the subsequent weeks,
      the lipid profile normalized, with the LDL cholesterol concentration particularly
      reduced at 55 mg/dL. CONCLUSION: Clinical expression of type III
      hyperlipoproteinemia necessitates interaction between an underlying genetic
      defect of lipoprotein metabolism (apo E2 homozygosity) and a secondary metabolic
      insult such as, in the current case, hypothyroidism and possibly breast-feeding
      mediated hypoestrogenemia. As such, in patients with type III
      hyperlipoproteinemia, it is essential to search for exacerbating factors,
      particularly because the amelioration of such factors may rectify the effects of
      the underlying dyslipidemia.

PMID- 16638728
TI  - Camurati-Engelmann disease in conjunction with hypogonadism.
AB  - OBJECTIVE: To report a case of Camurati-Engelmann disease (CED) in conjunction
      with hypogonadism, an association that has not been previously described.
      METHODS: We present the clinical, laboratory, and histopathologic features of our
      case. In addition, we review the molecular genetics of CED. RESULTS: CED is a
      rare autosomal dominant disorder of the skeleton, characterized by bilaterally
      symmetric, progressive dysplasia of the bones. The typical features of this
      disorder are hyperostotic and sclerotic changes in the bones, primarily of the
      extremities. Our patient, a 49-year-old male resident of a nursing home,
      presented with muscle weakness, waddling gait, bone pain, and increased
      fatigability, usual features of CED (which had been formally diagnosed when he
      was 8 years old). He also had hyponatremia, hyperkalemia, and almost undetectable
      serum testosterone. The gene responsible for CED has been mapped to the same
      locus as the gene for the synthesis of transforming growth factor (TGF-b 1).
      Mutations in the TGF b 1 gene have been identified in patients with CED. TGF-b 1
      also has an important role in reproductive function, both during embryogenesis
      and in adulthood. It has predominant effects on steroidogenesis as well as
      spermatogenesis. We discuss the hormonal and histopathologic changes in our
      patient and postulate that the association of CED with hypogonadism could be
      attributable to the impaired regulation of gonadal growth and steroidogenesis, in
      which TGF-b 1 has an important role. CONCLUSION: We propose that the association
      of CED with hypogonadism could be explained on the basis of a common underlying
      mutation in the TGF b 1 gene, leading to accumulation of excessive TGF-b 1.

PMID- 16638729
TI  - Secondary Cushing's syndrome after a single epidural injection of a
      corticosteroid.

PMID- 16638730
TI  - Idle thoughts from an addled mind: The importance of being important.

PMID- 16638731
TI  - Visual vignette.

PMID- 16638732
TI  - Visual vignette.

PMID- 16638733
TI  - Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for
      nonantiarrhythmic drugs: the International Conference on Harmonization of
      Technical Requirements for Registration of Pharmaceuticals for Human Use E14
      guideline.
AB  - Proarrhythmias due to drug-induced QT prolongation are the second most common
      cause for drug withdrawal and have caused increasing concern. Two new
      International Conference on Harmonization of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH) guidelines were recently
      endorsed in which nonclinical (S7B) and clinical (E14) methodologies are
      discussed and guidance is given to the industry. This commentary describes the
      key components of the E14 document, the impact of nonclinical testing on the
      clinical program, the thorough QT study, and the impact of its result on late
      stage development. The studies described in S7B and E14 will contribute to a
      better understanding of the link between nonclinical assays and QT prolongation
      in humans. Differences in interpretation among individual regulators in the major
      regions with respect to measures proposed in the E14 guideline might impact
      regional regulatory decisions. These differences include the value of nonclinical
      assays for the subsequent clinical testing and how predictive a negative thorough
      QT study result is for proarrhythmic risk in patients.

PMID- 16638734
TI  - Pharmacokinetics of buspirone in autistic children.
AB  - Buspirone is used to treat generalized anxiety disorder in children and may be
      useful in developmental disorders in which brain serotonin synthesis is altered.
      Autistic children (13 boys, 7 girls) were given a single oral dose of 2.5 mg (2-3
      years) or 5.0 mg (4-6 years). Blood was collected for 8 hours, and plasma was
      assayed for buspirone and its metabolite 1-pyrimidinylpiperazine (1-PP). The peak
      concentration of buspirone averaged 1141 +/- 748 pg/mL with a time to maximum
      concentration of 0.8 hours. Half-life was 1.6 +/- 0.3 hours. Peak concentrations
      of 1-PP were 4.5-fold higher than for buspirone. Girls had higher peak
      concentrations (1876 vs 746 pg/mL) for buspirone and a lower peak 1-PP/buspirone
      concentration ratio. These results suggest that buspirone is rapidly absorbed and
      eliminated in young children with extensive metabolism to 1-PP. Plasma
      concentrations with 2.5- to 5.0-mg doses were similar to those observed in older
      children receiving 7.5- to 15-mg doses.

PMID- 16638735
TI  - Reduced methylprednisolone clearance causing prolonged pharmacodynamics in a
      healthy subject was not associated with CYP3A5*3 allele or a change in diet
      composition.
AB  - The influence of diet and genetics was investigated in a healthy white person who
      had distinctly low methylprednisolone clearance. Pharmacokinetic and
      pharmacodynamic parameter values were similar on 2 occasions during the
      consumption of a low-carbohydrate diet and a Weight Watchers diet, indicating
      that the decreased clearance was unlikely attributable to a change in diet
      composition. Although the subject was found to be homozygous for CYP3A5*3,
      genetic findings were not significant for a number of other CYP3A4 and CYP3A5
      allelic variants. Because of the high prevalence of CYP3A5*3/*3 in whites and
      because 5 of 7 white control subjects are also homozygous for CYP3A5*3, this
      genotype cannot fully explain the reduced metabolism of the drug. Other genetic
      or contributing factors might have been involved. New polymerase chain reaction
      based genotyping methods for functionally defective CYP3A5*6, *8, *9, and *10
      alleles were developed in this study. These assays will be useful for CYP3A5
      genotype analysis in future clinical studies.

PMID- 16638736
TI  - CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of
      Durango, Mexico.
AB  - Although the drug-metabolizing enzyme CYP2D6 has been studied extensively in
      subjects of differing ethnicities, limited CYP2D6 pharmacogenetic data are
      available for the Amerindian population and Mestizos of Mexico. Dextromethorphan
      hydroxylation phenotype was studied in Tepehuano Amerindian (n = 58) and Mestizo
      (n = 88) subjects, and 195 individuals (85 Tepehuano Amerindians and 110
      Mestizos) were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism methods to identify the frequencies of the CYP2D6*3, *4, *6, and *10
      alleles. Tepehuano Amerindian subjects lacked the poor metabolizer (PM)
      phenotype, whereas in Mestizos the PM phenotype frequency was 6.8%. The CYP2D6*3,
      *6, and *10 alleles were not found in Tepehuano Amerindians. The CYP2D6*4 allele
      had a low frequency (0.006) in this Amerindian group. In the Mestizo group, the
      CYP2D6*3, *4, and *10 alleles had frequencies of 0.009, 0.131, and 0.023,
      respectively. The CYP2D6*6 allele was not found in Mestizos. The genotype
      phenotype association was strongly statistically significant (r(2) = .45; P =
      .005) in Mestizos. The Tepehuano population was found to have a low phenotypic
      and genotypic CYP2D6 diversity and differed from other Amerindian groups. On the
      other hand, the frequencies of the CYP2D6 variant alleles in Mestizos were
      similar to those reported for whites.

PMID- 16638737
TI  - Development of a predictive pharmacokinetic model for a novel cyclooxygenase-2
      inhibitor.
AB  - A predictive population pharmacokinetic model was developed for a novel
      cyclooxygenase-2 (COX-2) inhibitor CS-706, using data from 130 subjects in 3
      phase 1 trials after single or multiple doses of CS-706 (2- to 800-mg doses
      daily, up to 14 days) and validated using sparse data from a separate study. A 2
      compartment model described the data. Typical apparent clearance (CL/F) was 47.2
      L/h and was reduced by 43% at doses greater than 200 mg. Apparent clearance was
      decreased by 38% in female subjects and by 64% and 15%, respectively, in
      poor/intermediate CYP 2D6 and poor CYP 2C9 metabolizers. Typical apparent volume
      of the central compartment was 166 L and increased with body weight.
      Bioavailability increased by 42% after nighttime doses and decreased saturably
      with increasing dose (50% reduction at 221 mg). Predicted exposures in Japanese
      subjects were reduced relative to whites because of a lower frequency of poor
      metabolizers. The model may aid in optimizing the design of future studies and
      predicting exposures in other subpopulations.

PMID- 16638738
TI  - Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of
      BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy
      subjects.
AB  - To investigate the influence of food and administration of an antacid (aluminum
      magnesium hydroxide) or ranitidine on the absorption of BAY 59-7939
      (rivaroxaban), 4 randomized studies were performed in healthy male subjects. In 2
      food interaction studies, subjects received BAY 59-7939, either as two 5-mg
      tablets (fasted and fed), four 5-mg tablets (fasted), or one 20-mg tablet (fasted
      and fed). In 2 drug interaction studies, BAY 59-7939 (six 5-mg tablets) was given
      alone or with ranitidine (150 mg twice daily, preceded by a 3-day pretreatment
      phase) or antacid (10 mL). Plasma samples were obtained to assess pharmacokinetic
      and pharmacodynamic parameters of BAY 59-7939. In the presence of food, time to
      maximum concentration (t(max)) was delayed by 1.25 hours; maximum concentration
      (C(max)) and area under the curve (AUC) were increased, with reduced
      interindividual variability at higher doses of BAY 59-7939. Compared with
      baseline, BAY 59-7939 resulted in a relative increase in maximum prothrombin time
      (PT) prolongation of 44% (10 mg) and 53% (20 mg) in the fasted state, compared
      with 53% and 83% after food. Time to maximum PT prolongation was delayed by 0.5
      to 1.5 hours after food, with no relevant influence of food type. No significant
      difference in C(max) and AUC was observed with coadministration of BAY 59-7939
      and ranitidine or antacid.

PMID- 16638739
TI  - Absence of clinically relevant pharmacokinetic interaction between ribavirin and
      tenofovir in healthy subjects.
AB  - This was a 36-day, open-label, fixed-sequence, multiple-dose drug interaction
      study in 23 healthy subjects to evaluate the effects of multiple doses of
      tenofovir disoproxil fumarate on the single-dose pharmacokinetics of ribavirin.
      Subjects received a 600-mg once-daily oral dose of ribavirin on days 1 and 22 and
      300-mg once-daily oral doses of tenofovir disoproxil fumarate on days 17 through
      24. Pharmacokinetic sampling was performed on days 1 through 4 and 22 through 25.
      Pharmacokinetics of ribavirin was not altered by its coadministration with
      tenofovir disoproxil fumarate as the point estimates (day 22 [test treatment]/day
      1 [reference treatment]), and the 90% confidence interval for maximum observed
      concentration (0.95; 88.7-101) and area under the plasma concentration-time curve
      up to time of last measurable concentration (1.12; 106-117) were within the
      equivalence bounds of 80% to 125%. Tenofovir pharmacokinetics after ribavirin
      coadministration was similar to that observed in previous studies. These results
      indicate that coadministration of tenofovir disoproxil fumarate and ribavirin
      does not result in substantial changes to their individual pharmacokinetic
      profiles.

PMID- 16638740
TI  - Ritonavir has minimal impact on the pharmacokinetic disposition of a single dose
      of bupropion administered to human volunteers.
AB  - A drug-drug interaction study was conducted to determine whether ritonavir (200
      mg; 4 doses over 2 days) alters the pharmacokinetic disposition of bupropion (75
      mg; once) coadministered to 7 healthy volunteers in a placebo-controlled 2-way
      crossover study. Serum samples collected from 0 to 24 hours after bupropion
      administration were assayed for concentrations of bupropion and metabolites
      (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion). Derived
      pharmacokinetic parameters were compared between placebo/bupropion and
      ritonavir/bupropion trials by paired t test. The effect of ritonavir on most
      pharmacokinetic parameters was minimal (<20% mean change). The only parameters
      that showed a statistically significant effect were threohydrobupropion area
      under the blood concentration curve (14% +/- 5% decrease, mean +/- SE; P = .04)
      and erythrohydrobupropion time-to-maximal serum concentration (161% +/- 92%
      increase, P = .03), suggesting that ritonavir may inhibit the carbonyl reductase
      enzyme responsible for formation of these metabolites. These findings indicate
      that short-term ritonavir dosing has only minimal impact on the pharmacokinetic
      disposition of a single dose of bupropion in healthy volunteers.

PMID- 16638741
TI  - Evaluation of the drug interaction potential of aplaviroc, a novel human
      immunodeficiency virus entry inhibitor, using a modified cooperstown 5 + 1
      cocktail.
AB  - Aplaviroc is a novel CCR5 antagonist, a class of compounds under investigation as
      viral entry inhibitors for the treatment of human immunodeficiency virus
      infection. A modified Cooperstown 5+1 cocktail was used to assess the drug
      interaction potential of aplaviroc. Fifteen healthy subjects were administered
      single oral doses of caffeine (CYP1A2), warfarin (CYP2C9), omeprazole (CYP2C19),
      dextromethorphan (CYP2D6), and midazolam (CYP3A) alone (reference treatment) and
      during steady-state administration of aplaviroc (400 mg every 12 hours, test
      treatment). Metabolite-to-parent area under the plasma concentration versus time
      curve (AUC) ratios (paraxanthine/caffeine and 5-hydroxyomeprazole/omeprazole),
      oral clearance (S-warfarin), AUC (midazolam), and metabolite-to-parent urinary
      excretion ratio (dextrorphan/dextromethorphan) were determined. The test-to
      reference treatment ratios (geometric mean ratio and 90% confidence interval)
      were caffeine, 1.06 (0.97-1.17); S-warfarin, 0.93 (0.76-1.15); omeprazole, 1.07
      (0.98-1.16); dextromethorphan, 1.17 (0.97-1.42); midazolam, 1.30 (1.04-1.63). No
      significant inhibition of CYP1A2, CYP2C9, CYP2C19, or CYP2D6 enzyme activity was
      observed. Mild inhibition of CYP3A isozymes should not preclude the use of
      concomitant CYP3A substrates in future clinical studies with aplaviroc.

PMID- 16638742
TI  - The effect of montelukast on nasal mucociliary clearance.

PMID- 16638743
TI  - Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of
      fibroblast growth factor 23 requires O-glycosylation.
AB  - Mutations in the gene encoding the glycosyltransferase polypeptide GalNAc-T3,
      which is involved in initiation of O-glycosylation, were recently identified as a
      cause of the rare autosomal recessive metabolic disorder familial tumoral
      calcinosis (OMIM 211900). Familial tumoral calcinosis is associated with
      hyperphosphatemia and massive ectopic calcifications. Here, we demonstrate that
      the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23)
      requires O-glycosylation, and that GalNAc-T3 selectively directs O-glycosylation
      in a subtilisin-like proprotein convertase recognition sequence motif, which
      blocks processing of FGF23. The study suggests a novel posttranslational
      regulatory model of FGF23 involving competing O-glycosylation and protease
      processing to produce intact FGF23.

PMID- 16638744
TI  - The two Plasmodium falciparum nucleosome assembly proteins play distinct roles in
      histone transport and chromatin assembly.
AB  - The malarial parasite Plasmodium falciparum has two nucleosome assembly proteins,
      PfNapS and PfNapL (Chandra, B. R., Olivieri, A., Silvestrini, F., Alano, P., and
      Sharma, A. (2005) Mol. Biochem. Parasitol. 142, 237-247). We show that both
      PfNapS and PfNapL interact with histone oligomers but only PfNapS is able to
      deposit histones onto DNA. This property of PfNapS is divalent cation-dependent
      and ATP-independent. Deletion of the terminal subdomains of PfNapS abolishes its
      nucleosome assembly capabilities, but the truncated protein retains its ability
      to bind histones. Both PfNapS and PfNapL show binding to the linker histone H1
      suggesting their probable role in extraction of H1 from chromatin fibers. Our
      data suggests distinct sites of interaction for H1 versus H3/H4 on PfNapS. We
      show that PfNapS and PfNapL are phosphorylated both in vivo and in vitro by
      casein kinase-II, and this modification is specifically inhibited by heparin.
      Circular dichroism, fluorescence spectroscopy, and chymotrypsin fingerprinting
      data together suggest that PfNapL may undergo very small and subtle structural
      changes upon phosphorylation. Specifically, phosphorylation of PfNapL increases
      its affinity 3-fold for core histones H3, H4, and for the linker histone H1.
      Finally, we demonstrate that PfNapS is able to extract histones from both
      phosphorylated and unphosphorylated PfNapL, potentially for histone deposition
      onto DNA. Based on these results, we suggest that the P. falciparum NapL is
      involved in the nucleocytoplasmic relay of histones, whereas PfNapS is likely to
      be an integral part of the chromatin assembly motors in the parasite nucleus.

PMID- 16638745
TI  - The stimulus-induced tyrosine phosphorylation of Munc18c facilitates vesicle
      exocytosis.
AB  - Stimulus-induced tyrosine phosphorylation of Munc18c was investigated as a
      potential regulatory mechanism by which the Munc18c-Syntaxin 4 complex can be
      dissociated in response to divergent stimuli in multiple cell types. Use of
      [(32)P]orthophosphate incorporation, pervanadate treatment, and phosphotyrosine
      specific antibodies demonstrated that Munc18c underwent tyrosine phosphorylation.
      Phosphorylation was apparent under basal conditions, but levels were
      significantly increased within 5 min of glucose stimulation in MIN6 beta cells.
      Tyrosine phosphorylation of Munc18c was also detected in 3T3L1 adipocytes and
      increased with insulin stimulation, suggesting that this may be a conserved
      mechanism. Syntaxin 4 binding to Munc18c decreased as Munc18c phosphorylation
      levels increased in pervanadate-treated cells, suggesting that phosphorylation
      dissociates the Munc18c-Syntaxin 4 complex. Munc18c phosphorylation was localized
      to the N-terminal 255 residues. Mutagenesis of one residue in this region, Y219F,
      significantly increased the affinity of Munc18c for Syntaxin 4, whereas mutation
      of three other candidate sites was without effect. Moreover, Munc18c-Y219F
      expression in MIN6 cells functionally inhibited glucose-stimulated SNARE complex
      formation and insulin granule exocytosis. These data support a novel and
      conserved mechanism for the dissociation of Munc18c-Syntaxin 4 complexes in a
      stimulus-dependent manner to facilitate the increase in Syntaxin 4-VAMP2
      association and to promote vesicle/granule fusion.

PMID- 16638746
TI  - Characterization of native retinal fluorophores involved in biosynthesis of A2E
      and lipofuscin-associated retinopathies.
AB  - Mutations in the photoreceptor-specific ABCA4 gene are associated with several
      inherited retinal and macular degenerations. A prominent phenotype of these
      diseases is the accumulation of cytotoxic lipofuscin fluorophores such as A2E
      within the retinal pigment epithelium. Another compound, dihydro-N-retinylidene-N
      retinylphosphatidyl-ethanolamine (A2PE-H(2)), also accumulates in retinas of mice
      and humans harboring ABCA4 mutations and was proposed to be a precursor of A2E.
      The role of A2PE-H(2) in the biogenesis of A2E and its relationship to other
      retinal fluorophores has not been previously investigated. We report spectral
      properties and structural relationships of the principal retinal fluorophores
      that accumulate in retina and retinal pigment epithelium of abca4(-/-) mice. A
      long wavelength fluorescence emission intrinsic to abca4(-/-) retinal explants is
      shown to emanate from A2PE-H(2). All-trans retinal dimer conjugates, which were
      also identified in the retinal explants, possessed distinct fluorescence and
      structural properties and, unlike A2PE-H(2), did not accumulate in an age
      dependent manner. Derivative absorbance and fluorescence spectroscopy revealed
      that A2PE-H(2), A2E, and N-retinylidene-N-retinyl-phosphatidylethanolamine
      (A2PE), a known precursor of A2E, share common electronic and resonant
      structures. Importantly, collision-induced dissociation of A2PE-H(2) produced
      daughter ions that were identical to authentic A2E and its daughter ions.
      Finally, intravitreal administration of A2PE-H(2) to wild-type mice resulted in
      the formation of A2PE and A2E. These data validate a previously hypothesized
      biosynthetic pathway for A2E and implicate A2PE-H(2) as a precursor in this
      pathway. Fluorescence properties of A2PE-H(2) and other related fluorophores
      characterized in this report have significance for evaluation of human retinal
      diseases characterized by aberrant fundus autofluorescence.

PMID- 16638747
TI  - A basic leucine zipper transcription factor, G-box-binding factor 1, regulates
      blue light-mediated photomorphogenic growth in Arabidopsis.
AB  - Several transcriptional regulators have been identified and demonstrated to play
      either positive or negative regulatory roles in seedling development. However,
      the regulatory coordination between hypocotyl elongation and cotyledon expansion
      during early seedling development in plants remains unknown. We report the
      identification of a Z-box binding factor (ZBF2) and its functional
      characterization in cryptochrome-mediated blue light signaling. ZBF2 encodes a G
      box binding factor (GBF1), which is a basic leucine zipper transcription factor.
      Our DNA-protein interaction studies reveal that ZBF2/GBF1 also interacts with the
      Z-box light-responsive element of light-regulated promoters. Genetic analyses of
      gbf1 mutants and overexpression studies suggest that GBF1 acts as a repressor of
      blue light-mediated inhibition in hypocotyl elongation, however, it acts as a
      positive regulator of cotyledon expansion during photomorphogenic growth.
      Furthermore, whereas GBF1 acts as a positive regulator of lateral root formation,
      it differentially regulates the expression of light-inducible genes. Taken
      together, these results demonstrate that GBF1 is a unique transcriptional
      regulator of photomorphogenesis in blue light.

PMID- 16638748
TI  - FE65 interaction with the ApoE receptor ApoEr2.
AB  - The adaptor protein FE65 interacts with the beta-amyloid precursor protein (APP)
      via its C-terminal phosphotyrosine binding (PTB) domain and affects APP
      processing and Abeta production. Our previous data demonstrate that the apoE
      receptor ApoEr2 co-precipitated with APP and suggest that there are extracellular
      and intracellular interactions between these two transmembrane proteins. We
      hypothesized that FE65 acts as an intracellular link between ApoEr2 and APP. Co
      immunoprecipitation experiments in COS7 cells demonstrated an interaction between
      ApoEr2 and FE65 that depended on the N-terminal PTB domain of FE65. Full-length
      FE65 increased co-immunoprecipitation of ApoEr2 and APP. Full-length FE65 also
      increased surface expression of ApoEr2, as determined by surface protein
      biotinylation and live cell surface staining. Constructs containing both the C-
      and N-terminal PTB domains of FE65 increased secreted APP, secreted ApoEr2, APP C
      terminal fragment, and ApoEr2 C-terminal fragment, but constructs containing only
      single PTB domains did not affect APP or ApoEr2 processing. In addition, full
      length FE65 decreased Abeta to a significantly greater extent than individual
      FE65 domains. These data suggest that FE65 can bind APP and ApoEr2 at the same
      time and affect the processing of each.

PMID- 16638749
TI  - Functional implication of neuronal calcium sensor-1 and phosphoinositol 4-kinase
      beta interaction in regulated exocytosis of PC12 cells.
AB  - Several studies have shown that the neuronal calcium sensor (NCS-1) and
      phosphoinositol 4-kinase-beta (PI4K-beta) regulate the exocytotic process of
      nerve and neuroendocrine cells. The aim of our study was to investigate their
      possible interaction at rest and during stimulation in living cells and to
      decipher the role of this interaction in the secretory process. In PC12 cells, we
      observed a stimulation-induced recruitment of NCS-1 and PI4K-beta from the
      intracellular compartment toward the plasma membrane. This recruitment was highly
      correlated to the intracellular Ca(2+) rise induced by secretagogues. Using
      fluorescence resonance energy transfer between PI4K-beta-ECFP and NCS-1-EYFP, we
      show that both proteins are interacting in resting cells and that this
      interaction increases with stimulation. It appears that the membrane insertion of
      NCS-1 is necessary for the interaction with PI4K-beta, since a mutation that
      prevented the membrane insertion of NCS-1 abolished NCS-1-PI4K-beta interaction,
      as revealed by fluorescence resonance energy transfer analysis. Additionally, the
      overexpression of mutated NCS-1 prevents the stimulatory effect on secretion
      induced by PI4K-beta, suggesting that the interaction of the two proteins on a
      membrane compartment is necessary for the secretory function. Moreover,
      extinction of endogenous PI4K-beta by small interfering RNA inhibits secretion
      and completely prevents the stimulatory effect of NCS-1 on calcium-evoked
      exocytosis from permeabilized PC12 cells, showing directly for the first time the
      functional implication of a NCS-1.PI4K-beta complex in regulated exocytosis.

PMID- 16638750
TI  - Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer
      cells.
AB  - 12-Lipoxygenase utilizes arachidonic acid to synthesize 12(S)
      hydroperoxyeicosatetraenoic acid, which is converted to the end product 12(S)
      hydroxyeicosatetraenoic acid, an eicosanoid that promotes tumorigenesis and
      metastasis. Increased expression of 12-lipoxygenase has been documented in a
      number of carcinomas. When overexpressed in human prostate or breast cancer, 12
      lipoxygenase promotes tumor angiogenesis and growth in vivo. The present study
      was undertaken to delineate the mechanisms by which 12-lipoxygenase enhances
      angiogenesis. Herein we report that nordihydroguaiaretic acid, a pan inhibitor of
      lipoxygenases and baicalein, a selective inhibitor of 12-lipoxygenase, reduced
      VEGF expression in human prostate cancer PC-3 cells. Overexpression of 12
      lipoxygenase in PC-3 cells resulted in a 3-fold increase in VEGF protein level
      when compared with vector control cells. An increase in PI 3-kinase activity was
      found in 12-LOX-transfected PC-3 cells and inhibition of PI 3-kinase by LY294002
      significantly reduced VEGF expression. Northern blot and real time PCR analyses
      revealed an elevated VEGF transcript level in PC-3 cells transfected with a 12
      lipoxygenase expression construct. Using a VEGF promoter luciferase construct (
      1176/+54), we found a 10-fold increase in VEGF promoter activity in 12
      lipoxygenase-transfected PC-3 cells. The region located between -88 and -66 of
      the VEGF promoter was identified as 12-lipoxygenase responsive using VEGF
      promoter-based luciferase assays. Further analysis with mutant constructs
      indicated Sp1 as a transcription factor required for 12-lipoxygenase stimulation
      of VEGF. Neutralization of VEGF by a function-blocking antibody significantly
      decreased the ability of 12-lipoxygenase-transfected PC-3 cells to stimulate
      endothelial cell migration, suggesting VEGF as an important effector for 12
      lipoxygenase-mediated stimulation of tumor angiogenesis.

PMID- 16638752
TI  - Crystal structure of the herpes simplex virus 1 DNA polymerase.
AB  - Herpesviruses are the second leading cause of human viral diseases. Herpes
      Simplex Virus types 1 and 2 and Varicella-zoster virus produce neurotropic
      infections such as cutaneous and genital herpes, chickenpox, and shingles.
      Infections of a lymphotropic nature are caused by cytomegalovirus, HSV-6, HSV-7,
      and Epstein-Barr virus producing lymphoma, carcinoma, and congenital
      abnormalities. Yet another series of serious health problems are posed by
      infections in immunocompromised individuals. Common therapies for herpes viral
      infections employ nucleoside analogs, such as Acyclovir, and target the viral DNA
      polymerase, essential for viral DNA replication. Although clinically useful, this
      class of drugs exhibits a narrow antiviral spectrum, and resistance to these
      agents is an emerging problem for disease management. A better understanding of
      herpes virus replication will help the development of new safe and effective
      broad spectrum anti-herpetic drugs that fill an unmet need. Here, we present the
      first crystal structure of a herpesvirus polymerase, the Herpes Simplex Virus
      type 1 DNA polymerase, at 2.7 A resolution. The structural similarity of this
      polymerase to other alpha polymerases has allowed us to construct high confidence
      models of a replication complex of the polymerase and of Acyclovir as a DNA chain
      terminator. We propose a novel inhibition mechanism in which a representative of
      a series of non-nucleosidic viral polymerase inhibitors, the 4-oxo
      dihydroquinolines, binds at the polymerase active site interacting non-covalently
      with both the polymerase and the DNA duplex.

PMID- 16638753
TI  - An unusual twist: ventricular tachycardia induced by a loop in a right
      ventricular pacing wire.

PMID- 16638754
TI  - The economic cost of invasive pneumococcal disease and the potential for
      reduction by vaccination in an adult population in South Yorkshire.

PMID- 16638756
TI  - Mental capacity assessments and discharge decisions.

PMID- 16638757
TI  - A short performance test can help to predict adherence to self-administration of
      insulin in elderly patients with diabetes.

PMID- 16638758
TI  - Depression and anxiety in elderly patients with chronic obstructive pulmonary
      disease.

PMID- 16638759
TI  - A pilot study on the use of dolls for people with dementia.

PMID- 16638760
TI  - Predicting catastrophic decline in mobility among older people.
AB  - OBJECTIVE: to investigate the associations between chronic health conditions,
      psychosocial and environmental factors and catastrophic decline in mobility among
      older people. DESIGN: longitudinal cohort. SETTING: national sample living in
      private households. PARTICIPANTS: nine hundred and ninety-nine adults aged > or =
      65 years at initial interview, of which 786 agreed to take part in a follow-up
      survey 12 months later, and 531 responded to the questionnaire. MEASUREMENTS:
      catastrophic decline in mobility: inability to do any of the three activities of
      daily living items-walking 400 yards, climbing up and down stairs or steps and
      getting on a bus-having been capable of independently doing all three one year
      earlier. RESULTS: similar annual rates of catastrophic decline were reported for
      men and women: 4.8 [95% confidence interval (CI) 2.7-8.3] and 4.6% (2.4-8.6),
      respectively. Strong associations were found between catastrophic decline and age
      > 70 years, hearing problems and health deterioration, odds ratio (OR) 3.7 (95%
      CI 1.1-11.8), 2.8 (1.1-7.3) and 4.3 (1.2-14.7), respectively. Poor perceptions of
      health, loss of control and feeling fearful also appeared to be important: below
      average summary psychological status, OR 6.5 (1.9-22.3). Inability to do heavy
      housework, carry heavy shopping or bend to cut own toenails, indicating poor
      functional reserve capacity, was strongly associated with decline, OR 6.8 (2.2
      20.8). CONCLUSION: psychosocial factors are as strongly associated with
      catastrophic decline as deterioration in health status. Interventions to reduce
      the risk of catastrophic decline may require management of psychosocial problems
      as well as health condition components.

PMID- 16638761
TI  - Factors affecting completion of the SF-36 in older people.
AB  - OBJECTIVE: to examine the influence of specific clinical impairments and
      disabilities on the completion of the SF-36 health status measure among older
      people. DESIGN: Prospective observational study. SETTING/PARTICIPANTS: An SF-36
      was administered to 245 subjects aged 65 years and older. Subjects were chosen by
      sampling from a variety of inpatient, outpatient and community sources to ensure
      a range of relevant disabilities. MEASUREMENTS: response rates, overall rates of
      completion, completion of individual questions and time taken to complete.
      RESULTS: severe functional impairment (Barthel index < or = 12) was found in
      22.4% (51/228), cognitive impairment in 54.1% (132/244), depressed mood in 77.0%
      (151/196) and visuospatial dysfunction in 71.3% (134/188). The median number of
      impairments was three (interquartile range 1-4). Specific physical impairments
      were visual in 13.2% (31/235), hearing in 30.2% (74/245), impaired manual
      dexterity in 18.0% (44/245) and dysphasia in 23% (55/239). In multivariate
      analyses, global functional impairment (P = 0.006), cognitive impairment (P =
      0.0001) and impaired manual dexterity (P = 0.005) were significantly associated
      with more dimensions uncompleted, whilst cognitive impairment (P = 0.001), age (P
      = 0.006) and visuospatial dysfunction (P = 0.0003) were significantly associated
      with longer completion times. CONCLUSION: the most striking finding of the study
      was that global rather than specific physical and mental dysfunction was
      associated with the inability to complete the SF-36 questionnaire. The difficulty
      appears to lie in the performance of a complex task, rather than with specific
      aspects of the task which could be overcome by adaptation or aids. Our experience
      is that this relatively complex questionnaire does not adequately measure
      functional health status in disabled older people because of non-completion and
      may therefore overestimate the health of populations.

PMID- 16638762
TI  - Maintaining the art of conversation in Parkinson's disease.

PMID- 16638763
TI  - Assessment of patients in long-term care should be used to improve quality as
      well as allocate funds.

PMID- 16638764
TI  - Impact of ASCOT on hypertension treatment and guidelines in older adults.

PMID- 16638765
TI  - Sleep-related problems of Parkinson's disease.
AB  - OBJECTIVE: To define the epidemiology, characteristics and aetiology of nocturnal
      symptoms and sleep disorders in patients with Parkinson's disease (PD) and
      evaluate the available methods for their diagnosis and management. METHODS: A
      review of the English-language literature pertaining to sleep disturbances
      associated with PD, using the Medline database and bibliographies in relevant
      articles. RESULTS: Sleep-related problems specific to PD may occur early and even
      predate the diagnosis of the disease but are generally more frequent and more
      severe in patients with advanced PD. These problems can seriously compromise
      patients' quality of life and lead to impaired functioning in daily activities.
      Scales designed specifically for the assessment of sleep problems in patients
      with PD have recently been developed. Evidence base for the treatment of sleep
      disturbances in PD is poor, and only nocturnal akinesia, excessive day-time
      sleepiness and rapid eye movement behaviour disorder have been partially
      addressed. CONCLUSIONS: Sleep disorders associated with PD are a common and under
      recognised problem. The assessment of sleep should be part of the routine
      evaluation of patients with PD, and large-scale controlled therapeutic trials are
      necessary.

PMID- 16638766
TI  - The influence of patient and carer age in access to palliative care services.
AB  - BACKGROUND: Older patients are less likely to receive palliative care than
      younger patients. As patient and primary carer age correlate positively, patterns
      may be due to carer rather than patient age, and reflect better ability to obtain
      support among younger carers. OBJECTIVE: To investigate how both patient and
      carer age relate to palliative care use, controlling for relevant variables.
      DESIGN: Comparison of patients who received community Macmillan nurse specialist
      advice, Marie Curie nursing or inpatient hospice care with patients who did not,
      using univariate analysis and multivariate logistic regression. Patient and carer
      data were collected through electronic service record linkage and carer post
      bereavement interviews. SAMPLE: patients referred to a hospice at home service
      whose primary carer could be interviewed (n = 123). RESULTS: Whilst a cancer
      diagnosis was an important determinant of access for all services considered,
      logistic regression shows that carer age, but not patient age, and hospice at
      home access predicted Marie Curie nursing use. Both patient and carer age
      predicted use of Macmillan nurse advice. Age of the patient, but not carer age,
      predicted admission to inpatient hospice, alongside requiring care for over a
      month (all P < 0.05). CONCLUSIONS: Carer age may be as important a predictor of
      palliative home care use as patient age. We need to investigate whether younger
      carers have greater support needs or show greater effectiveness in obtaining help
      and to assess whether older carers need more assistance in recruitment of
      support.

PMID- 16638767
TI  - Relationships between long-term stroke disability, handicap and health-related
      quality of life.
AB  - OBJECTIVES: To estimate levels of disability, handicap and health-related quality
      of life (HRQOL) up to 3 years after stroke and examine the relationships between
      these domains. DESIGN: A longitudinal, observational study SETTING: Population
      based register of first-ever strokes METHODS: Subjects, registered between 1
      January 1995 and 31 December 1997, were assessed at 1 year (n = 490) and 3 years
      (n = 342) post-stroke for disability [Barthel index (BI)], handicap [Frenchay
      activity index (FAI)] and HRQOL (SF-36). BI was categorised as severe, moderate,
      mild and independent (0-9, 10-14, 15-19 and 20); FAI was categorised as inactive,
      moderately active and very active (0-15, 16-30 and 31-45). SF-36 domains include:
      Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health
      (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE) and Mental
      Health (MH). Physical (PHSS) and Mental Health (MHSS) Summary Scores were
      computed. RESULTS: at 1 and 3 years, 26.1 and 26.3%, respectively, were disabled
      (BI < 15); 55 and 51%, respectively, were handicapped (FAI = 0-15); and survivors
      had low mean PHSS (37.1 and 37.9), but satisfactory mean MHSS (46.6 and 47.7).
      There was a graded positive relationship between all SF-36 domains and the
      categories of BI and FAI. Spearman rank correlations were significant between BI
      and all SF-36 domains at both time points: strong (r > 0.70) with PF, moderate (r
      = 0.31-0.70) with RP, SF and PHSS, but weak (r < 0.30) with other domains.
      Correlations between FAI and SF-36 domains were strong with PF, weak with BP, RE
      and MHSS, and moderate with other domains. CONCLUSIONS: Disability and handicap
      remain highly prevalent up to 3 years after stroke. Patients' perception of
      physical health is persistently low, but mental health perception is satisfactory
      up to 3 years. Due to variable correlations between different HRQOL domains with
      disability and handicap, it is suggested that disability, handicap and HRQOL
      should all be assessed to acquire a broader measure of stroke outcome.

PMID- 16638768
TI  - Clinical outcome of older patients with acute coronary syndrome over the last
      three decades.
AB  - OBJECTIVE: To Evaluate the clinical outcome of patients with acute coronary
      syndrome (ACS) in the Coronary Care Unit (CCU) over three decades in Dunedin, New
      Zealand. DESIGN: Registry study. SETTING AND PATIENTS: all consecutive patients
      (n = 3,013) with ACS admitted to the CCU from 1979 to 1981 (n = 966) and from
      1989 to 1991 (n = 1470) were included prospectively. Data on ACS patients managed
      in the CCU in 2001-2002 (n = 577) were obtained via medical chart review.
      RESULTS: There was a rising proportion of older (> or = 75 years of age) patients
      with ACS (3.8% in 1979-1981, 15.2% in 1989-1991 and 25.6% in 2001-2002, P <
      0.0005). However, we observed a progressive reduction of in-hospital mortality
      for ACS (10.7, 7.3 and 5.0%, P < 0.005) and for ST-elevation myocardial
      infarction (STEMI) (18.4, 16.1 and 6.6%, P < 0.005). The progressive fall in
      mortality rate was also observed amongst older patients, both for ACS (27, 19.2
      and 11.5%, P = 0.011) and for STEMI (34.8, 30.9 and 15.4%, P < 0.005). Of
      concern, only 10% of patients presented within 1 h of symptom onset and 50%
      within 5 h, and this has not changed over three decades. The variables associated
      with < 5 h from symptom onset to presentation were men [odds ratio (OR) 1.25, 95%
      confidence interval (CI) 1.10-1.42, P = 0.001], a history of ischaemic heart
      disease (OR 1.25, 95% CI 1.09-1.43, P = 0.002) and STEMI (OR 1.41, 95% CI 1.18
      1.67, P < 0.0001). Advanced age was not a predictor for late presentation.
      CONCLUSIONS: Over the past three decades, more old patients were treated in the
      CCU. However, there was a decline in hospital mortality, particularly for STEMI.
      Further efforts are required to decrease the time to presentation.

PMID- 16638769
TI  - Severity assessment criteria recommended by the British Thoracic Society (BTS)
      for community-acquired pneumonia (CAP) and older patients. Should SOAR (systolic
      blood pressure, oxygenation, age and respiratory rate) criteria be used in older
      people? A compilation study of two prospective cohorts.
AB  - OBJECTIVES: To assess the usefulness of the British Thoracic Society guidelines
      for severity assessment of community-acquired pneumonia (CAP) in predicting
      mortality and to explore alternative criteria which could be more useful in older
      patients. DESIGN: Compilation study of two prospective observational cohorts.
      SETTING AND PARTICIPANTS: A University hospital in Norfolk, UK with a catchment
      population of 568,000. Subjects were 195 patients (median age = 77 years) who
      were included in two prospective studies of CAP. MAIN OUTCOME MEASURE: All-cause
      mortality occurring within the 6 week follow-up. RESULTS: sensitivity,
      specificity, positive and negative predictive values for study outcome using CURB
      and CURB-65 were assessed in 189 patients, and CRB-65 in 192 patients out of a
      total of 195 patients. Our results were comparable with the original study by Lim
      et al. Although CURB-65 and CRB-65 included age criteria, in effect they did not
      materially improve the specificity in predicting high-risk patients in both
      studies. We found that oxygenation measured by ventilation perfusion mismatch
      (PaO2:FiO2) was the best predictor of outcome in this slightly older cohort [odds
      ratio (OR) = 0.99 (0.98-0.99), P = 0.0001]. We derived a new set of criteria;
      SOAR (systolic blood pressure, oxygenation, age and respiratory rate) based on
      our findings. Their sensitivity, specificity, positive and negative predictive
      values were 81.0% (58.1-94.6), 59.3% (49.6-68.4), 27.0% (16.6-39.7) and 94.4%
      (86.2-98.4), respectively, confirming their comparability with existing criteria.
      CONCLUSIONS: Our Study confirms the usefulness of currently recommended severity
      rules for CAP in this older cohort. SOAR criteria may be useful as alternative
      criteria for a better identification of severe CAP in advanced age where both
      raised urea level above 7 mmol/l and confusion are common.

PMID- 16638770
TI  - Cardiopulmonary responses to eccentric and concentric resistance exercise in
      older adults.
AB  - BACKGROUND: In older ambulatory persons, exercise strategies that are expected to
      generate beneficial muscle adaptations with low cardiopulmonary demands are
      needed. OBJECTIVE: We hypothesised that eccentric resistance exercise would be
      less demanding on the cardiovascular and pulmonary systems than bouts of
      concentric resistance exercise. DESIGN: The effects of eccentric and concentric
      resistance exercise were compared during leg squats at a submaximal intensity
      known to increase muscle mass. SUBJECTS: 19 Older persons (15 women/four men, age
      65 +/- 4 years) and 19 young reference controls (10 women/nine men; age 25 +/- 2
      years) were enrolled. METHODS: Participants completed eccentric-only and
      concentric-only exercise bouts 5-7 days apart. RESULTS: Cardiovascular and
      pulmonary measures were collected from subjects during bouts consisting of three
      sequential sets of 10 repetitions at 65% of their voluntary concentric 1
      repetition maximum force (68+/-16 kg for older participants and 94 +/- 36 kg for
      young participants). Peak heart rate (119 +/- 10 versus 155 +/- 16 b.p.m.),
      systolic blood pressure (129 +/- 18 versus 167 +/- 14 mmHg), cardiac index (7.8
      +/- 2.0 versus 9.2 +/- 1.5 l/min/m2) and expired ventilation (20.5 +/- 5.7 versus
      29.8 +/- 9.1 l/min) were significantly lower during eccentric than during
      concentric bouts in the older subjects, respectively (P < 0.001 for all
      comparisons). Similarly, peak heart rate, systolic blood pressure, cardiac index
      and expired ventilation were significantly lower during eccentric bouts in the
      young control subjects. CONCLUSIONS: Eccentric resistance exercise produced less
      cardiopulmonary demands and may be better suited for older persons with low
      exercise tolerance and at risk of adverse cardiopulmonary events.

PMID- 16638771
TI  - Postural, physiological and psychological reactions to challenging balance: does
      age make a difference?
AB  - OBJECTIVES: To determine if increases in balance challenge influenced concomitant
      change in self-efficacy, state anxiety and physiological arousal, and if these
      changes were correlated with changes in standing balance in young and older
      adults. DESIGN: A 2 x 2 between- (age) by within-subject (balance challenge)
      factorial design. SETTING: quiet standing trials were performed on low and high
      support-surface heights in a research laboratory. SUBJECTS: 14 Young (22-31
      years) and 14 older (60-83 years) adults with no known neurological or balance
      disorders, or falls within the last year. METHODS: Forceplate-derived measures of
      standing balance, measures of state anxiety, blood pressure and task-specific
      balance and coping self-efficacy. RESULTS: Independent of age, mean position,
      amplitude and frequency of centre of pressure displacements were significantly
      influenced by surface height, as were anxiety and efficacy. Decreased amplitude
      and increased frequency changes observed in both age groups with increased
      balance challenge were consistent with a stiffening strategy. Blood pressure,
      state anxiety and self-efficacy were correlated with different postural control
      changes in young and older adults. CONCLUSIONS: Older adults used the same
      stiffening strategy as young adults to cope with the increased anxiety and
      lowered confidence associated with standing on a high surface. Converging
      evidence indicates that physiological status, state anxiety and balance efficacy
      are related to specific changes in postural performance with increased balance
      challenge. Findings highlight the potential additive effects of psychological and
      physiological factors on clinical balance performance and the need to consider
      comprehensive rehabilitation and prevention techniques that concern psychological
      and physiological contributions to balance deficits.

PMID- 16638772
TI  - Inability to draw intersecting pentagons as a predictor of unsatisfactory
      spirometry technique in elderly hospital inpatients.

PMID- 16638773
TI  - NHS continuing care: reliable decisions?

PMID- 16638774
TI  - A mysterious case of normalising blood sugar: insulinoma in a long-standing
      diabetic patient.
AB  - We report a case of recurrent hypoglycaemia in a long-standing type 2 diabetic
      patient, despite dramatic reduction in her anti-diabetic therapy. Subsequent
      investigations revealed an insulinoma as the cause. This patient was treated
      medically with diazoxide therapy, as multiple co-morbidities were felt to
      preclude surgical intervention. Although insulinoma is rare in the elderly and
      exceedingly rare in the context of type 2 diabetes, it should be given due
      consideration when no other exacerbating factor is found.

PMID- 16638775
TI  - Ventriculomegaly or symptomatic hydrocephalus? Beware of atypical neurological
      syndromes.

PMID- 16638776
TI  - Cholestatic jaundice following carbimazole therapy in an elderly thyrotoxic
      patient.

PMID- 16638777
TI  - The future of geriatric medicine.

PMID- 16638778
TI  - Re: Predictors of 1-year mortality in patients discharged from the hospital
      following acute exacerbation of chronic obstructive pulmonary disease.

PMID- 16638779
TI  - ERCP in the elderly: more than just the age factor.

PMID- 16638780
TI  - Borges on classification.

PMID- 16638781
TI  - Postnatal weight increase and growth velocity of very low birthweight infants.
AB  - BACKGROUND: Only a few studies have dealt with postnatal growth velocity of very
      low birthweight (VLBW) infants. OBJECTIVE: To analyse weight growth kinetics of
      VLBW infants from birth to over 2 years of age. PATIENTS: A total of 262 VLBW
      infants were selected; inaccurate estimate of gestational age, major congenital
      anomalies, necrotising enterocolitis, death, and loss to follow up within the
      first year were the exclusion criteria. METHODS: Body weight was recorded daily
      up to 28 days or up to discontinuation of parenteral nutrition, weekly up to
      discharge, then at 1, 3, 6, 9, 12, 18, and 24 months of corrected age. Individual
      growth profiles were fitted with a seven constant, exponential-logistic function
      suitable for modelling weight loss and weight recovery, two peaks, and the
      subsequent slow decrease in growth velocity. RESULTS: After a postnatal weight
      loss, all infants showed a late neonatal peak of growth velocity between the 7th
      and 21st weeks; most also experienced an early neonatal peak between the 2nd and
      6th week. VLBW infants who were small for gestational age and those with major
      morbidities grew less than reference VLBW infants who were the appropriate size
      for gestational age without major morbidities: at 2 years of age, the difference
      in weight was about 860 g. The more severe growth impairment seen in VLBW infants
      with major morbidities is almost entirely due to the reduced height of the late
      neonatal peak of velocity. CONCLUSIONS: The growth model presented here should be
      a useful tool for evaluating to what extent different pathological conditions or
      nutritional and medical care protocols affect growth kinetics.

PMID- 16638782
TI  - Effect of delayed sampling on umbilical cord arterial and venous lactate and
      blood gases in clamped and unclamped vessels.
AB  - BACKGROUND: Cord blood lactate at birth is a marker of antenatal hypoxia, and is
      comparable to pH as a prognostic tool. OBJECTIVE: To determine, by a prospective
      observational study, the effect of delayed sampling from arteries and veins that
      were double clamped to isolate the blood from the placenta (clamped), and from
      vessels that were not isolated from the placenta (unclamped). METHODS: Paired
      samples taken from clamped and unclamped vessels at 0, 20, 40, and 60 minutes
      were analysed for lactate, base excess, pH, and Pco(2). Data were analysed as the
      change from time 0 at 20, 40, and 60 minutes. RESULTS: Thirty eight placentas of
      infants delivered by elective caesarean section were studied. Arterial samples
      were taken from 20 placentas, and venous samples from 18 placentas. Arterial and
      venous lactate was significantly higher than at time 0 by 20 minutes in both
      clamped and unclamped vessels. Changes in unclamped vessels were greater than in
      clamped vessels. The pH remained unchanged over 60 minutes in clamped vessels,
      but changed significantly in unclamped vessels. Base excess changed significantly
      in both clamped and unclamped vessels. CONCLUSIONS: Cord blood samples taken
      after 20 minutes delay are unreliable for lactate measurement, even if the vessel
      has been doubly clamped to isolate the blood from the placenta. Current
      guidelines that state that blood can be sampled from a clamped cord for up to one
      hour after delivery should not apply to the interpretation of lactate or base
      excess. Delayed sampling from unclamped cords is very unreliable.

PMID- 16638783
TI  - Who best to make the assessment? Professionals' and families' classifications of
      gross motor function in cerebral palsy are highly consistent.
AB  - AIM: To determine the reliability of family assessment for the Gross Motor
      Function Classification System (GMFCS) for children with cerebral palsy in the
      UK. METHODS: Families of a complete geographically defined population of children
      with cerebral palsy between 6 and 12 years old were identified from the 4Child
      epidemiological database. Postal surveys were conducted with the families and any
      of the child's health professionals that were nominated by the families. RESULTS:
      Families of 129/314 eligible children took part in the study (41%). The indices
      of agreement and reliability between families and professionals were also
      equivalent to those observed between the professionals (kappa = 0.5, ICC > or =
      0.9). Reliability coefficients were higher when more of the professionals
      classified children using direct observation rather than only reviewing their
      clinical records. CONCLUSIONS: Despite excellent reliability, families and
      professionals did not always agree exactly on a child's GMFCS level.
      Classifications may differ due to children's varying performance in different
      environments, in which case families will almost certainly know their children's
      ability in a broader range of settings. The indices of reliability of family
      assessment for the GMFCS meet the recommended criteria for use with individuals
      and groups, indicating that the method is suitable for use in research studies
      and clinical practice.

PMID- 16638784
TI  - Impact of adverse publicity on MMR vaccine uptake: a population based analysis of
      vaccine uptake records for one million children, born 1987-2004.
AB  - AIMS: To determine the impact of adverse publicity on MMR uptake and measles
      susceptibility, including whether vaccination is delayed and the role of
      deprivation. METHODS: A population database for all Scotland containing
      immunisation records for over one million children (n = 1,079,327) born 1987-2004
      was analysed. MMR uptake was determined by birth cohort and deprivation category.
      "Final" uptake (at approx age 6 years) was predicted by linear regression by
      birth cohort. Measles susceptibility in 1998 and 2003 was determined by postcode
      sector and district for cohorts combined to construct nursery and primary school
      age groups. RESULTS: There is evidence of a slight rise in late uptake, but
      insufficient to compensate for underlying declines. Late vaccination continues to
      be associated with deprivation, while the most affluent tend to be vaccinated
      promptly, or not at all. Predicted figures for "final" MMR1 uptake are over 90%,
      but under 95%. Measles susceptibility has increased significantly in nursery
      children, with an eightfold rise in the number of districts with greater than 20%
      susceptibility in this group (from 3 to 25). CONCLUSIONS: Increased measles
      susceptibility in nursery children is concerning, particularly in the most
      vulnerable areas. These figures are likely to increase in the future, as MMR
      uptake has not yet returned to the previous higher level. Increased
      susceptibility levels can also be expected in primary schools in the future, as
      levels of late uptake are insufficient to compensate. Predicted figures for
      "final" MMR1 uptake are under the herd immunity threshold and campaigns may be
      required to increase uptake among future primary school children.

PMID- 16638785
TI  - A prospective study of the immediate and delayed adverse events following
      intravenous immunoglobulin infusions.
AB  - AIM: To document the incidence of immediate and delayed adverse events (AE)
      following intravenous immunoglobulin (IVIG) infusion in children. METHODS:
      Immediate and delayed adverse events were prospectively recorded for 345
      infusions in 58 children receiving IVIG for immunodeficiency (n = 33) or
      immunomodulation (n = 25). For each infusion adverse events were documented
      during the infusion and by follow up interview 4-7 days later. RESULTS: Immediate
      adverse events occurred in 10.3% and delayed adverse events in 41.4% of children
      treated during the study period. Three and a half per cent of the infusions were
      associated with immediate AE and 20.9% with delayed adverse events. Headache was
      the most common delayed AE, occurring in 24.1% of patients and 12.8% of
      infusions. CONCLUSIONS: Delayed adverse events to IVIG infusions are common in
      children. They occur more frequently than immediate adverse events and are the
      cause of significant morbidity. Recognition of the high frequency of delayed
      adverse events is important in the care of children receiving IVIG therapy.

PMID- 16638786
TI  - Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions.
AB  - BACKGROUND: Deregulation of cell cycle plays an important role in tumorigenesis.
      Cyclin D1 gene (CCND1) is a key regulator of the G(1) phase of the cell cycle.
      METHODS: In this case-control study of 115 oral premalignant lesion (OPL)
      patients and 230 controls, we genotyped the CCND1 single nucleotide polymorphism
      (SNP) at the exon 4 splice site (G870A) and determined the association of this
      SNP with the risk of developing OPLs. RESULTS: We found significant associations
      between the heterozygous variant allele (GA), the homozygous variant allele (AA)
      and OPL risk, with adjusted odds ratios (ORs) of 1.91 [95% confidence interval
      (CI), 1.05-3.48] and 2.38 (95% CI, 1.16-4.87), respectively. The OR for
      individuals with at least one variant allele was 2.04 (95% CI, 1.15-3.60). When
      further stratified analyses were performed, the increased risk was more evident
      in younger individuals (OR = 2.82; 95% CI, 1.32-6.02), in men (OR = 2.97; 95%CI,
      1.31-6.71) and in never smokers (OR = 2.92; 95% CI, 1.09-7.82). Finally, we found
      joint effects between the variant alleles and the smoking status. Using never
      smokers with the wild-type (GG) genotypes as the reference group, the ORs for
      never smokers with the variant genotypes (G/A + A/A), smokers with the G/G
      genotype and smokers with the G/A + A/A genotypes were 2.92 (1.09-7.82), 3.95
      (1.36-11.5) and 7.01 (2.68-18.4), respectively. CONCLUSION: Our results suggest
      that the CCND1 G870A SNP may contribute to genetic susceptibility to OPLs and
      involve in oral cancer development.

PMID- 16638787
TI  - Green tea, black tea and colorectal cancer risk: a meta-analysis of epidemiologic
      studies.
AB  - Experimental studies have supported tea as a chemopreventive agent for colorectal
      cancer. No quantitative summary of the epidemiologic evidence on tea and
      colorectal cancer risk has ever been performed. The current meta-analysis
      included 25 papers conducted in 11 countries across three continents (North
      America, Asia and Europe). Summary odds ratios (ORs) for highest versus
      non/lowest tea consumption levels were calculated based on fixed and random
      effects models. The meta-regression and stratified methods were used to examine
      heterogeneity across studies. For green tea, the combined results from eight
      studies indicated a reduced risk of colorectal cancer with intake [summary OR =
      0.82, 95% confidence interval (CI) = 0.69-0.98]. The protective effect is mainly
      found among the three case-control studies of colon cancer (summary OR = 0.74,
      95% CI = 0.60-0.93). Results from studies of rectal cancer irrespective of study
      design (case-control versus cohort) (summary OR = 0.99, 95% CI = 0.71-1.37) and
      cohort studies of colon cancer (summary OR = 0.99, 95% CI = 0.79-1.24) were
      compatible with the null hypothesis. For black tea, the summary OR derived from
      20 studies was 0.99 (95% CI = 0.87-1.13). There is wide divergence in results
      across the 20 individual studies; formal tests for homogeneity across studies
      revealed statistically significant differences in findings across all studies (P
      < 0.001), amongst the 7 cohort studies (P = 0.002), and amongst the 13 case
      control studies (P < 0.001). Despite the strong evidence from in vitro and non
      human in vivo studies in support of green and black tea as potential
      chemopreventive agents against colorectal cancer, available epidemiologic data
      are insufficient to conclude that either tea type may protect against colorectal
      cancer in humans.

PMID- 16638788
TI  - Audit of resource use in patients with non-organic disorders admitted to a UK
      neurology unit.

PMID- 16638789
TI  - Subarachnoid haemorrhage in patients > or = 75 years: clinical course, treatment
      and outcome.
AB  - BACKGROUND: The number of elderly patients being admitted with aneurysmal
      subarachnoid haemorrhage (SAH) has been increasing. Treatment of the aneurysm may
      be offset by the higher rate of surgical or endovascular complications. AIM: To
      study the clinical condition at onset, complications during clinical course,
      treatment and outcome in a consecutive series of elderly patients. METHODS:
      Patients who were > or = 75 years at the onset of SAH were selected from the
      databases of two hospitals. Data on clinical condition at onset (poor condition
      defined as World Federation of Neurological Surgeons (WFNS) Scale IV and V),
      clinical course, treatment and outcome were extracted. Univariate and
      multivariate regression analyses were carried out to identify predictors for in
      hospital death and poor outcome, defined as death or dependency. RESULTS: The
      data of 170 patients were retrieved, of whom 25 (15%) patients were independent
      at discharge; none of these patients had been admitted in a poor condition. Poor
      clinical condition on admission (odds ratio (OR) 7.9; 95% confidence interval
      (CI) 3.7 to 17) and recurrent haemorrhage (OR 7.5; 95% CI 2.5 to 23) were the
      strongest predictors for in-hospital death. Recurrent haemorrhage was the
      strongest predictor for poor outcome in the subset of patients who were admitted
      in good clinical condition. In all, 10 of 47 (21%) patients were independent at
      discharge after neurosurgical clipping (n = 34) or endovascular coiling (n = 13).
      CONCLUSION: Elderly patients with SAH have a poor prognosis. The effect of the
      initial haemorrhage is the most common reason for poor outcome. For patients who
      are admitted in good clinical condition, the most important complication leading
      to poor outcome is recurrent haemorrhage. Treatment of the aneurysm in patients >
      or = 75 years is feasible, may improve the outcome and should be strongly
      considered in patients who are admitted in a good condition.

PMID- 16638790
TI  - Low folate levels may protect against colorectal cancer.
AB  - BACKGROUND AND AIMS: Dietary folate is believed to protect against colorectal
      cancer (CRC). However, few studies have addressed the role of circulating levels
      of folate. The aim of this study was to relate prediagnostic plasma folate and
      homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR)
      677C>T and 1298A>C polymorphisms to the risk of developing CRC. SUBJECTS:
      Subjects were 226 cases and 437 matched referents from the population based
      Northern Sweden Health and Disease Cohort. RESULTS: We observed a bell-shaped
      association between plasma folate concentrations and CRC risk; multivariate odds
      ratio for middle versus lowest quintile 2.00 (95% confidence interval (CI) 1.13
      3.56). In subjects with follow up times greater than the median of 4.2 years
      however, plasma folate concentrations were strongly positively related to CRC
      risk; multivariate odds ratio for highest versus lowest quintile 3.87 (95% CI
      1.52-9.87; p trend = 0.007). Homocysteine was not associated with CRC risk.
      Multivariate odds ratios for the MTHFR polymorphisms were, for 677 TT versus CC,
      0.41 (95% CI 0.19-0.85; p trend = 0.062), and for 1298 CC versus AA, 1.62 (95% CI
      0.94-2.81; p trend = 0.028). Interaction analysis suggested that the result for
      1298A>C may have been largely due to linkage disequilibrium with 677C>T. The
      reduced CRC risk in 677 TT homozygotes was independent of plasma folate status.
      CONCLUSIONS: Our findings suggest a decreased CRC risk in subjects with low
      folate status. This possibility of a detrimental component to the role of folate
      in carcinogenesis could have implications in the ongoing debate in Europe
      concerning mandatory folate fortification of foods.

PMID- 16638791
TI  - Probiotics prevent bacterial translocation and improve intestinal barrier
      function in rats following chronic psychological stress.
AB  - BACKGROUND AND AIMS: Chronic psychological stress, including water avoidance
      stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal
      defences against luminal bacteria. The aim of this study was to determine the
      ability of a defined probiotic regimen to prevent WAS induced intestinal
      pathophysiology. METHODS: Male rats were subjected to either WAS or sham stress
      for one hour per day for 10 consecutive days. Additional animals received seven
      days of Lactobacillus helveticus and L rhamnosus in the drinking water prior to
      stress and remained on these probiotics for the duration of the study. Rats were
      then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric
      lymph nodes cultured to determine bacterial translocation. RESULTS: All animals
      remained healthy for the duration of the study. Chronic WAS induced excess ion
      secretion (elevated baseline short circuit current) and barrier dysfunction
      (increased conductance) in both the ileum and colon, associated with increased
      bacterial adhesion and penetration into surface epithelial cells. Approximately
      70% of rats subjected to WAS had bacterial translocation to mesenteric lymph
      nodes while there was no bacterial translocation in controls. Probiotic
      pretreatment alone had no effect on intestinal barrier function. However, WAS
      induced increased ileal short circuit current was reduced with probiotics whereas
      there was no impact on altered conductance. Pretreatment of animals with
      probiotics also completely abrogated WAS induced bacterial adhesion and prevented
      translocation of bacteria to mesenteric lymph nodes. CONCLUSION: These findings
      indicate that probiotics can prevent chronic stress induced intestinal
      abnormalities and, thereby, exert beneficial effects in the intestinal tract.

PMID- 16638792
TI  - An early look at ten state HIFA Medicaid waivers.
AB  - In an examination of ten Health Insurance Flexibility and Accountability (HIFA)
      demonstrations, a major Medicaid initiative of the Bush administration, we found
      that states have adopted varied program designs, reflecting their particular
      goals and circumstances. Nationally, we estimate that 300,000 people were covered
      under HIFA demonstrations as of December 2005. Although this is a sizable number,
      coverage has fallen far short of the 820,000 expected.

PMID- 16638793
TI  - TennCare--a failure of politics, not policy: a conversation with Gordon Bonnyman.
      Interview by Robert E. Hurley.
AB  - Gordon Bonnyman is the indefatigable advocate who has spent the past dozen years
      both championing and challenging TennCare, Tennessee's controversial Medicaid
      program. As the executive director of the Tennessee Justice Center, Bonnyman has
      advocated for TennCare during three gubernatorial administrations; this advocacy
      reached new levels of intensity in 2005, when Gov. Phil Bredesen introduced major
      cutbacks to the program. Bonnyman's prominent role in shaping TennCare and,
      according to some, stymieing changes to it publicly pitted him against Governor
      Bredesen in the battle to "save" TennCare.

PMID- 16638794
TI  - The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a
      study of 26 cases.
AB  - We studied 26 patients belonging to 20 families with a disorder caused by
      mutations in the POLG gene. The patients were homozygous for 1399 G/A or 2243 G/C
      (giving the amino acid changes A467T and W748S, respectively) or compound
      heterozygotes for these two mutations. Irrespective of genotype, the patients
      exhibited a progressive neurological disorder usually starting in their teens and
      characterized by epilepsy, headache, ataxia, neuropathy, myoclonus and late onset
      ophthalmoplegia. However, major differences in survival were seen depending on
      genotype, with compound heterozygotes having a significantly shorter survival
      time than patients homozygous either for the A467T or W748S (P = 0.006). Epilepsy
      occurred in 22 of the 26 patients and in the majority of these there was an
      occipital EEG focus. Episodes of both generalized and focal motor status
      epilepticus were common and highly resistant to treatment, even with generalized
      anaesthesia. Status epilepticus was the recorded cause of death in 9 of 11
      patients. Liver failure was the sole cause of death in two patients and evolved
      terminally in six others, all but one of whom were being treated with sodium
      valproate. Two patients underwent liver transplantation, but only one survived.
      Delayed psychomotor development and subsequent cognitive decline also occurs.
      This study demonstrates the clinical spectrum of a disorder that combines
      features of Alpers' syndrome and a later onset mitochondrial spinocerebellar
      ataxia with epilepsy and headache. Patients with this disorder are at high risk
      of death from status epilepticus and from liver failure, if exposed to sodium
      valproate. Each mutation appears capable of producing a disorder that is
      recessively inherited, although we also find evidence in one patient suggesting
      that heterozygotes may manifest. Compound heterozygotes have a significantly more
      severe phenotype raising the possibility of a dominant negative effect.

PMID- 16638795
TI  - Mechanisms of spontaneous confabulations: a strategic retrieval account.
AB  - The 'temporality' hypothesis of confabulation posits that confabulations are true
      memories displaced in time, while the 'strategic retrieval' hypothesis suggests a
      general retrieval failure of which temporal confusion is a common symptom. Four
      confabulating patients with rupture of an anterior communicating artery (ACoA)
      aneurysm, eight non-confabulating ACoA controls and 16 normal controls
      participated in three experiments designed to test the two hypotheses. In
      Experiment 1, participants were tested on two continuous recognition tasks, one
      requiring temporal context distinctions, previously shown to be sensitive to
      confabulation and another that only requires content distinctions. Both
      manipulations were sensitive to confabulation, but not specific to it. Temporal
      context and content confusions (TCCs and CCs) can be explained as failures to
      make fine-grained distinctions within memory. In Experiment 2, free recall of
      semantic narratives that require strategic retrieval but are independent of
      temporal context was used to induce confabulations associated with remote memory,
      acquired before the onset of amnesia. Confabulators produced significantly more
      errors. Thus, when retrieval demands are equated, confabulations can be induced
      in the absence of temporal confusions. Only confabulators conflated semantic
      content from different remote semantic narratives and introduced idiosyncratic
      content, suggesting that qualitatively different mechanisms are responsible for
      distortions due to normal memory failure and for confabulation. Lesion analyses
      revealed that damage to ventromedial prefrontal cortex is sufficient for temporal
      context errors to occur, but additional orbitofrontal damage is crucial for
      spontaneous confabulation. In Experiment 3, we tested whether failure in memory
      monitoring is crucial for confabulation. Recognition of details from semantic and
      autobiographical narratives was used to minimize the initiation and search
      components of strategic retrieval. Only confabulators made more false alarms on
      both tasks, endorsed even highly implausible lures related to autobiographical
      events and were indiscriminately confident about their choices. These findings
      support a strategic retrieval account of confabulation of which monitoring is a
      critical component. Post-retrieval monitoring has at least two components: one is
      early, rapid and pre-conscious and the other is conscious and elaborate. Failure
      of at least the former is necessary and sufficient for confabulation. Other
      deficits, including TCC and CC, may be required for spontaneous confabulations to
      arise. The confluence of different sub-components of strategic retrieval would
      determine the content of confabulation and exacerbate its occurrence.

PMID- 16638796
TI  - Dynamics of language reorganization after stroke.
AB  - Previous functional imaging studies of chronic stroke patients with aphasia
      suggest that recovery of language occurs in a pre-existing, bilateral network
      with an upregulation of undamaged areas and a recruitment of perilesional tissue
      and homologue right language areas. The present study aimed at identifying the
      dynamics of reorganization in the language system by repeated functional MRI
      (fMRI) examinations with parallel language testing from the acute to the chronic
      stage. We examined 14 patients with aphasia due to an infarction of the left
      middle cerebral artery territory and an age-matched control group with an
      auditory comprehension task in an event-related design. Control subjects were
      scanned once, whereas patients were scanned repeatedly at three consecutive
      dates. All patients recovered clinically as shown by a set of aphasia tests. In
      the acute phase [mean: 1.8 days post-stroke (dps)], patients' group analysis
      showed little early activation of non-infarcted left-hemispheric language
      structures, while in the subacute phase (mean: 12.1 dps) a large increase of
      activation in the bilateral language network with peak activation in the right
      Broca-homologue (BHo) was observed. A direct comparison of both examinations
      revealed the strongest increase of activation in the right BHo and supplementary
      motor area (SMA). These upregulated areas also showed the strongest correlation
      between improved language function and increased activation (r(BHo) = 0.88,
      r(SMA) = 0.92). In the chronic phase (mean: 321 dps), a normalization of
      activation with a re-shift of peak activation to left-hemispheric language areas
      was observed, associated with further language improvement. The data suggest that
      brain reorganization during language recovery proceeds in three phases: a
      strongly reduced activation of remaining left language areas in the acute phase
      is followed by an upregulation with recruitment of homologue language zones,
      which correlates with language improvement. Thereafter, a normalization of
      activation is observed, possibly reflecting consolidation in the language system.

PMID- 16638797
TI  - Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in
      protein labeling.
AB  - The specific reaction of O6-alkylguanine-DNA alkyltransferase (AGT) with O6
      benzylguanine (BG) derivatives allows for a specific labeling of AGT fusion
      proteins with chemically diverse compounds in living cells and in vitro. The
      efficiency of the labeling depends on a number of factors, most importantly on
      the reactivity, selectivity and stability of AGT. Here, we report the use of
      directed evolution and two different selection systems to further increase the
      activity of AGT towards BG derivatives by a factor of 17 and demonstrate the
      advantages of this mutant for the specific labeling of AGT fusion proteins
      displayed on the surface of mammalian cells. The results furthermore identify two
      regions of the protein outside the active site that influence the activity of the
      protein towards BG derivatives.

PMID- 16638798
TI  - Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from
      rheumatic diseases.
AB  - OBJECTIVES: Although it has been reported that the numbers of both CD4(-)CD8(-)
      and CD4(+) natural killer T (NKT) cells are selectively decreased in the
      peripheral blood of patients with rheumatic diseases, there have been no reports
      concerning a novel subpopulation of CD8(+) NKT cells. To examine whether
      CD161(+)CD8(+) T cells, which are closely related to CD8(+) NKT cells, are also
      decreased in patients with rheumatic diseases, we have investigated the
      expression of CD161, together with that of CD28, CD25 and CD62L, on T cells in
      the peripheral blood of these patients. METHODS: The rheumatic diseases evaluated
      in this study were systemic lupus erythematosus (SLE) (n= 54), mixed connective
      tissue disease (MCTD) (n= 15), systemic sclerosis (SSc) (n= 14),
      polymyositis/dermatomyositis (PM/DM) (n= 13) and rheumatoid arthritis (RA) (n=
      24). Healthy donors were examined as controls (n= 18). The expression of CD161,
      CD28, CD25 and CD62L on T cells was analysed by flow cytometry. RESULTS: Both the
      frequency of CD161 expression on CD8(+) cells and the absolute number of
      CD161(+)CD8(+) cells were significantly decreased in patients with SLE, MCTD, SSc
      and PM/DM. Only the absolute number of CD161(+)CD8(+) T cells was significantly
      decreased in RA. CD161 expression on CD28(-)CD8(+) T cells was significantly
      decreased in SLE, MCTD and SSc. The absolute number of CD161(+)CD8(+)CD62L(-) T
      cells was significantly decreased in SLE, MCTD and SSc. CONCLUSIONS: Both the
      frequency and the absolute number of CD161(+)CD8(+) T cells were decreased in the
      peripheral blood of patients suffering from SLE, MCTD, SSc and PM/DM. This result
      suggests that there is also an abnormality of NKT cells in the CD8(+) population.

PMID- 16638799
TI  - An electronic logbook for rheumatologists performing musculoskeletal ultrasound.

PMID- 16638800
TI  - Pneumococcal and influenza vaccination in patients with rheumatic conditions and
      receiving DMARD therapy.

PMID- 16638801
TI  - A genome-scale assessment of peripheral blood B-cell molecular homeostasis in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: While rheumatoid arthritis (RA) is considered a prototypical
      autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully
      delineated. METHODS: We performed microarray expression profiling of peripheral
      blood B-cells from RA patients and controls. Data were analysed using
      differential gene expression analysis and 'gene networking' analysis
      (characterizing clusters of functionally inter-relelated genes) to identify both
      regulatory genes and the pathways in which they participate. Results were
      confirmed by quantitative real-time polymerase chain reaction and by measuring
      the levels of 10 serum cytokines involved in the pathways identified. RESULTS:
      Genes regulating and effecting the cell-cycle, proliferation, apoptosis,
      autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were
      differentially expressed in RA B-cells. Moreover, the serum levels of several
      soluble factors that modulate these pathways, including IL-1beta, IL-5, IL-6, IL
      10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA
      patients. CONCLUSIONS: These results outline aspects of the multifaceted role B
      cells play in RA pathogenesis in which immune dysregulation in RA modulates B
      cell biology and thereby contributes to the induction and perpetuation of a
      pathogenic humoral immune response.

PMID- 16638802
TI  - Sustained improvement of a girl affected with Devic's disease over 2 years of
      mycophenolate mofetil treatment.

PMID- 16638803
TI  - Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval
      zebrafish pronephros.
AB  - Megalin/LRP2 is an endocytic receptor in the proximal tubules of the mammalian
      kidney that plays a central role in the clearance of metabolites from the
      glomerular filtrate. To establish a genetic model system for elucidation of
      molecular components of this retrieval pathway, we characterized orthologous
      transport processes in the zebrafish. We show that expression of megalin/LRP2 and
      its co-receptor cubilin is conserved in the larval zebrafish pronephros and
      demarcates a segment of the pronephric duct that is active in clearance of tracer
      from the ultrafiltrate. Knock-down of megalin/LRP2 causes lack of Rab4-positive
      endosomes in the proximal pronephric duct epithelium and abrogates apical
      endocytosis. Similarly, knock-down of the megalin/LRP2 adaptor Disabled 2 also
      blocks renal clearance processes. These results demonstrate the conservation of
      the megalin/LRP2 retrieval pathway between the larval zebrafish pronephros and
      the mammalian kidney and set the stage for dissection of the renal endocytic
      machinery in a simple model organism. Using this model system, we provide first
      genetic evidence that renal tubular endocytosis and formation of endosomes is a
      ligand-induced process that crucially depends on megalin/LRP2 activity.

PMID- 16638804
TI  - Acquisition and extinction of gene expression programs are separable events in
      heterokaryon reprogramming.
AB  - Although differentiated cells normally retain cell-type-specific gene expression
      patterns throughout their lifetime, cell identity can sometimes be modified or
      reversed in vivo by transdifferentiation, or experimentally through cell fusion
      or by nuclear transfer. To examine the epigenetic changes that are required for
      the dominant conversion of lymphocytes to muscle, we generated heterokaryons
      between human B lymphocytes and mouse C2C12 myotubes. We show that within 2 days
      of heterokaryon formation lymphocyte nuclei adopt an architecture resembling that
      of muscle and then initiate the expression of muscle-specific genes in the same
      temporal order as developing muscle. The establishment of this muscle-specific
      program is coordinated with the shutdown of several lymphocyte-associated genes.
      Interestingly, erasing lymphocyte identity in reprogrammed cells requires histone
      deacetylase (HDAC) activity. Inhibition of HDAC activity during reprogramming
      selectively blocks the silencing of lymphocyte-specific genes but does not
      prevent the establishment of muscle-specific gene expression. Successful
      reprogramming is therefore shown to be a multi-step process in which the
      acquisition and extinction of lineage-specific gene programs are separable
      events.

PMID- 16638805
TI  - Regulation of pancreatic beta-cell insulin secretion by actin cytoskeleton
      remodelling: role of gelsolin and cooperation with the MAPK signalling pathway.
AB  - We have previously isolated two MIN6 beta-cell sublines, B1, highly responsive to
      glucose-stimulated insulin secretion, and C3, markedly refractory (Lilla, V.,
      Webb, G., Rickenbach, K., Maturana, A., Steiner, D. F., Halban, P. A. and
      Irminger, J. C. (2003) Endocrinology 144, 1368-1379). We now demonstrate that C3
      cells have substantially increased amounts of F-actin stress fibres whereas B1
      cells have shorter cortical F-actin. Consistent with these data, B1 cells display
      glucose-dependent actin remodelling whereas, in C3 cells, F-actin is refractory
      to this secretagogue. Furthermore, F-actin depolymerisation with latrunculin B
      restores glucose-stimulated insulin secretion in C3 cells. In parallel, glucose
      stimulated ERK1/2 activation is greater in B1 than in C3 cells, and is
      potentiated in both sublines following F-actin depolymerisation. Glucose
      activated phosphoERK1/2 accumulates at actin filament tips adjacent to the plasma
      membrane, indicating that these are the main sites of action for this kinase
      during insulin secretion. In addition, B1 cell expression of the calcium
      dependent F-actin severing protein gelsolin is >100-fold higher than that of C3
      cells. Knock-down of gelsolin reduced glucose-stimulated insulin secretion,
      whereas gelsolin over-expression potentiated secretion from B1 cells. Gelsolin
      localised along depolymerised actin fibres after glucose stimulation. Taken
      together, these data demonstrate that F-actin reorganization prior to insulin
      secretion requires gelsolin and plays a role in the glucose-dependent MAPK signal
      transduction that regulates beta-cell insulin secretion.

PMID- 16638806
TI  - Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6
      complex to orient apical membrane polarity.
AB  - The basolateral tumor suppressor protein Lgl is important for the regulation of
      epithelial cell polarity and tissue morphology. Recent studies have shown a
      physical and functional interaction of Lgl with another polarity-regulating
      protein machinery, the apical PAR-3-aPKC-PAR-6 complex, in epithelial cells.
      However, the mechanism of Lgl-mediated regulation of epithelial cell polarity
      remains obscure. By an siRNA method, we here show that endogenous Lgl is required
      for the disassembly of apical membrane domains in depolarizing MDCK cells induced
      by Ca2+ depletion. Importantly, this Lgl function is mediated by the suppression
      of the apical PAR-3-aPKC-PAR-6 complex activity. Analysis using 2D- or 3D
      cultured cells in collagen gel suggests the importance of this suppressive
      regulation of Lgl on the collagen-mediated re-establishment of apical membrane
      domains and lumen formation. These results indicate that basolateral Lgl plays a
      crucial role in the disassembly of apical membrane domains to induce the
      orientation of apical membrane polarity, which is mediated by the suppression of
      apical PAR-3-aPKC-PAR-6 complex activity.

PMID- 16638807
TI  - The junctional SR protein JP-45 affects the functional expression of the voltage
      dependent Ca2+ channel Cav1.1.
AB  - JP-45, an integral protein of the junctional face membrane of the skeletal muscle
      sarcoplasmic reticulum (SR), colocalizes with its Ca2+ -release channel (the
      ryanodine receptor), and interacts with calsequestrin and the skeletal-muscle
      dihydropyridine receptor Cav1. We have identified the domains of JP-45 and the
      Cav1.1 involved in this interaction, and investigated the functional effect of JP
      45. The cytoplasmic domain of JP-45, comprising residues 1-80, interacts with
      Cav1.1. JP-45 interacts with two distinct and functionally relevant domains of
      Cav1.1, the I-II loop and the C-terminal region. Interaction between JP-45 and
      the I-II loop occurs through the alpha-interacting domain in the I-II loop.
      beta1a, a Cav1 subunit, also interacts with the cytosolic domain of JP-45, and
      its presence drastically reduces the interaction between JP-45 and the I-II loop.
      The functional effect of JP-45 on Cav1.1 activity was assessed by investigating
      charge movement in differentiated C2C12 myotubes after overexpression or
      depletion of JP-45. Overexpression of JP-45 decreased peak charge-movement and
      shifted VQ1/2 to a more negative potential (-10 mV). JP-45 depletion decreased
      both the content of Cav1.1 and peak charge-movements. Our data demonstrate that
      JP-45 is an important protein for functional expression of voltage-dependent Ca2+
      channels.

PMID- 16638808
TI  - Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for
      inhibition of host cell apoptosis.
AB  - Infection with the intracellular parasite Toxoplasma gondii renders cells
      resistant to multiple pro-apoptotic signals, but underlying mechanisms have not
      been delineated. The phosphoinositide 3-kinase (PI 3-kinase) pathway and the
      immediate downstream effector protein kinase B (PKB/Akt) play important roles in
      cell survival and apoptosis inhibition. Here, we show that Toxoplasma infection
      of mouse macrophages activates PKB/Akt in vivo and in vitro. In a mixed
      population of infected and non-infected macrophages, activation is only observed
      in parasite-infected cells. The PI 3-kinase inhibitors wortmannin and LY294002
      block parasite-induced PKB phosphorylation. PKB activation occurs independently
      of Toll-like receptor adaptor protein MyD88 but uncoupling of Gi-protein-mediated
      signaling with pertussis toxin prevents PKB phosphorylation. Moreover, in the
      presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation
      but also ERK1/2 activation during T. gondii infection is defective. Most
      importantly, the parasite's ability to induce macrophage resistance to pro
      apoptotic signaling is prevented by incubation with PI 3-kinase inhibitors. This
      study demonstrates that T. gondii exploits host Gi-protein-dependent PI 3-kinase
      signaling to prevent induction of apoptosis in infected macrophages.

PMID- 16638809
TI  - Endocytosis of GABAB receptors modulates membrane excitability in the single
      celled organism Paramecium.
AB  - GABAB receptors modulate swimming behavior in Paramecium by inhibiting
      dihydropyridine-sensitive Ca2+ channels via G-proteins. Prolonged occupancy of
      GABAB receptors by baclofen results in a decrease in GABAB receptor functions.
      Since changes in the number of cell-surface GABAA receptors have been postulated
      to be of importance in modulating inhibitory synaptic transmission in neurons, we
      have studied the cell-surface expression and maintenance of GABAB receptors in P.
      primaurelia. In this study, we use immunostaining in electron and confocal
      microscopy to demonstrate that constitutive internalization of GABAB receptors in
      P. primaurelia is mediated by clathrin-dependent and -independent endocytosis.
      Indeed, GABAB receptors colocalize with the adaptin complex AP2, which is
      implicated in the selective recruitment of integral membrane proteins to clathrin
      coated vesicles, and with caveolin 1, which is associated with uncoated membrane
      invaginations. Furthermore, when endocytosis is blocked with hypertonic medium,
      cytosol acidification, filipin or with a peptide that disrupts the association
      between amphiphysin and dynamin, the effect of baclofen on swimming is increased.
      These results suggest that GABAB receptor endocytosis into clathrin-coated and 
      uncoated vesicles represents an important mechanism in the modulation of swimming
      behavior in Paramecium.

PMID- 16638810
TI  - Identification of regulators of germ layer morphogenesis using proteomics in
      zebrafish.
AB  - During vertebrate gastrulation, a well-orchestrated series of morphogenetic
      changes leads to the formation of the three germ layers: the ectoderm, mesoderm
      and endoderm. The analysis of gene expression patterns during gastrulation has
      been central to the identification of genes involved in germ layer formation.
      However, many proteins are regulated on a translational or post-translational
      level and are thus undetectable by gene expression analysis. Therefore, we
      developed a 2D-gel-based comparative proteomic approach to target proteins
      involved in germ layer morphogenesis during zebrafish gastrulation. Proteomes of
      ectodermal and mesendodermal progenitor cells were compared and 35 significantly
      regulated proteins were identified by mass spectrometry, including several
      proteins with predicted functions in cytoskeletal organization. A comparison of
      our proteomic results with data obtained in an accompanying microarray-based gene
      expression analysis revealed no significant overlap, confirming the complementary
      nature of proteomics and transcriptomics. The regulation of ezrin2, which was
      identified based on a reduction in spot intensity in mesendodermal cells, was
      independently validated. Furthermore, we show that ezrin2 is activated by
      phosphorylation in mesendodermal cells and is required for proper germ layer
      morphogenesis. We demonstrate the feasibility of proteomics in zebrafish,
      concluding that proteomics is a valuable tool for analysis of early development.

PMID- 16638811
TI  - Ca2+ -linked upregulation and mitochondrial production of nitric oxide in the
      mouse preimplantation embryo.
AB  - Previous studies have demonstrated a role for the signalling agent nitric oxide
      in regulating preimplantation embryo development. We have now investigated the
      biochemical mode of action of nitric oxide in mouse embryos in terms of
      mitochondrial function and Ca2+ signalling. DETA-NONOate, a nitric oxide donor,
      decreased day 4 blastocyst cell number and oxygen consumption, consistent with a
      role for nitric oxide in the inhibition mitochondrial cytochrome c oxidase. Using
      live cell imaging and the nitric-oxide-sensitive probe DAF-FM diacetate, nitric
      oxide was detected at all stages of preimplantation development and FRET analysis
      revealed a proportion of the nitric oxide to be colocalised with mitochondria.
      This suggests that mitochondria of preimplantation embryos produce nitric oxide
      to regulate their own oxygen consumption. Inhibiting or uncoupling the electron
      transport chain induced an increase in nitric oxide and [Ca2+]i as well as
      disruption of Ca2+ deposits at the plasma membrane, suggesting that mitochondrial
      disruption can quickly compromise cellular function through Ca2+ -stimulated
      nitric oxide production. A link between antimycin-A-induced apoptosis and nitric
      oxide signalling is proposed.

PMID- 16638812
TI  - Motor protein KIFC5A interacts with Nubp1 and Nubp2, and is implicated in the
      regulation of centrosome duplication.
AB  - Inhibition of motor protein activity has been linked with defects in the
      formation of poles in the spindle of dividing cells. However, the molecular
      mechanisms underlying the functional relationship between motor activity and
      centrosome dynamics have remained uncharacterised. Here, we characterise KIFC5A,
      a mouse kinesin-like protein that is highly expressed in dividing cells and
      tissues, and is subject to developmental and cell-type-specific regulation.
      KIFC5A is a minus-end-directed, microtubule-dependent motor that produces
      velocities of up to 1.26 microm minute(-1) in gliding assays and possesses
      microtubule bundling activity. It is nuclear in interphase, localises to the
      centre of the two microtubule asters at the beginning of mitosis, and to spindle
      microtubules in later mitotic phases. Overexpression of KIFC5A in mouse cells
      causes the formation of aberrant, non-separated microtubule asters and mitotic
      arrest in a prometaphase-like state. KIFC5A knockdown partly rescues the
      phenotype caused by inhibition of plus-end-directed motor Eg5 by monastrol on the
      mitotic spindle, indicating that it is involved in the balance of forces
      determining bipolar spindle assembly and integrity. Silencing of KIFC5A also
      results in centrosome amplification detectable throughout the cell cycle.
      Supernumerary centrosomes arise primarily as a result of reduplication and partly
      as a result of cytokinesis defects. They contain duplicated centrioles and have
      the ability to organise microtubule asters, resulting in the formation of
      multipolar spindles. We show that KIFC5A interacts with nucleotide-binding
      proteins 1 and 2 (Nubp1 and Nubp2), which have extensive sequence similarity to
      prokaryotic division-site-determining protein MinD. Nubp1 and Nubp2 also interact
      with each other. Knockdown of Nubp1 or double knockdown of Nubp1 and Nubp2
      (Nubp1&Nubp2) both phenocopy the KIFC5A silencing effect. These results implicate
      KIFC5A and the Nubp proteins in a common regulatory pathway involved in the
      control of centrosome duplication in mammalian cells.

PMID- 16638813
TI  - Myosin light chain phosphorylation regulates barrier function by remodeling tight
      junction structure.
AB  - Epithelial tight junctions form a barrier against passive paracellular flux. This
      barrier is regulated by complex physiologic and pathophysiologic signals that
      acutely fine-tune tight junction permeability. Although actomyosin contraction
      and myosin light chain phosphorylation are clearly involved in some forms of
      tight junction regulation, the contributions of other signaling events and the
      role of myosin light chain phosphorylation in this response are poorly
      understood. Here we ask if activation of myosin light chain kinase alone is
      sufficient to induce downstream tight junction regulation. We use a confluent
      polarized intestinal epithelial cell model system in which constitutively active
      myosin light chain kinase, tMLCK, is expressed using an inducible promoter. tMLCK
      expression increases myosin light chain phosphorylation, reorganizes
      perijunctional F-actin, and increases tight junction permeability. TJ proteins ZO
      1 and occludin are markedly redistributed, morphologically and biochemically, but
      effects on claudin-1 and claudin-2 are limited. tMLCK inhibition prevents changes
      in barrier function and tight junction organization induced by tMLCK expression,
      suggesting that these events both require myosin light chain phosphorylation. We
      conclude that myosin light chain phosphorylation alone is sufficient to induce
      tight junction regulation and provide new insights into the molecular mechanisms
      that mediate this regulation.

PMID- 16638814
TI  - Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in
      nucleolar organization.
AB  - The microtubule-associated tau protein participates in the organization and
      integrity of the neuronal cytoskeleton. A nuclear form of tau has been described
      in neuronal and non-neuronal cells, which displays a nucleolar localization
      during interphase but is associated with nucleolar-organizing regions in mitotic
      cells. In the present study, based on immunofluorescence, immuno-FISH and
      confocal microscopy, we show that nuclear tau is mainly present at the internal
      periphery of nucleoli, partially colocalizing with the nucleolar protein
      nucleolin and human AT-rich alpha-satellite DNA sequences organized as
      constitutive heterochromatin. By using gel retardation, we demonstrate that tau
      not only colocalizes with, but also specifically binds to, AT-rich satellite DNA
      sequences apparently through the recognition of AT-rich DNA stretches. Here we
      propose a functional role for nuclear tau in relation to the nucleolar
      organization and/or heterochromatinization of a portion of RNA genes. Since
      nuclear tau has also been found in neurons from patients with Alzheimer's disease
      (AD), aberrant nuclear tau could affect the nucleolar organization during the
      course of AD. We discuss nucleolar tau associated with AT-rich alpha-satellite
      DNA sequences as a potential molecular link between trisomy 21 and AD.

PMID- 16638815
TI  - Economy and mortality in Eastern and Western Europe between 1945 and 1990: the
      largest medical trial of history.

PMID- 16638817
TI  - Uterine contractility in response to different prostaglandins: results from
      extracorporeally perfused non-pregnant swine uteri.
AB  - BACKGROUND: Prostaglandins (PGs) are important stimulators of uterine
      contractility. Limited data are available at present on the effects of different
      PGs on uterine contractility, measured using intraluminal pressure changes in the
      complete uterus. The goal of this study was to assess dynamic changes in uterine
      contractility and peristalsis in response to PGs in comparison with the effects
      of oxytocin administration. METHODS: An extracorporeal perfusion model of swine
      uteri was used, which keeps the uterus in a functional condition, and is
      appropriate for the study of physiological questions. Oxytocin- and PG-induced
      uterine contractility and peristalsis were assessed using an intrauterine double
      chip microcatheter. RESULTS: A dose-dependent increase in intrauterine pressure
      (IUP) in the isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was
      observed after the administration of PGF(2alpha) and oxytocin, which reached a
      plateau after further stimulation. A dose-dependent increase in IUP in the
      isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was also observed
      after the administration of PGE(1) and PGE(2), with a plateau in IUP in the
      middle-concentration range and a decrease in the course of further stimulation.
      PGE(2) caused significantly more contractions starting in the corpus uteri and
      moving to the isthmus uteri (P = 0.008). The direction of most contractions
      caused by PGE(1), PGE(2) and oxytocin differed from that of PGF(2alpha).
      CONCLUSIONS: This study demonstrates that the PGs tested modulate contractility
      in non-pregnant swine uteri in a characteristic way, resulting in different
      contractility patterns.

PMID- 16638818
TI  - Factors influencing midazolam hydroxylation activity in human liver microsomes.
AB  - The cytochrome P450 3A (CYP3A) subfamily (mainly CYP3A4 and CYP3A5) is
      responsible for metabolizing approximately half of currently marketed drugs, but
      with considerable interindividual variability in expression and function. To
      investigate factors contributing to this variability, rates of midazolam (MDZ) 1'
      hydroxylation and CYP3A4 and CYP3A5 protein content were determined using a set
      of 54 human liver microsomes (HLMs). Genetic factors investigated included CYP3A4
      and CYP3A5 single nucleotide polymorphisms (SNPs) and haplotypes, CYP3A4 mRNA
      alternative splicing, and CYP3A4 transcriptional start and polyadenylation sites.
      Demographic and environmental factors investigated included age, gender, and
      histories of smoking and alcohol consumption. MDZ 1'-hydroxylation rates varied
      from 0.025 to 3.106 nmol/min/mg protein, with significant correlation to CYP3A4
      protein content (r(s) = 0.92, P < 0.001) but less robust correlation to CYP3A5
      protein content (r(s) = 0.60, P < 0.001). We identified eight CYP3A4 SNPs (five
      novel) and nine CYP3A5 SNPs (one novel), as well as seven CYP3A4 and two CYP3A5
      haplotypes (all novel). No influence of genotype or haplotype on MDZ 1'
      hydroxylation rate was observed, although CYP3A5*3A (g.6986a>g; g.31611c>t)
      carriers had lower CYP3A5 protein content compared with noncarriers (P = 0.004).
      No alternative splicing of CYP3A4 mRNA was found. Likewise, only a single
      transcriptional start site and polyadenylation site for CYP3A4 mRNA were
      identified. Subjects with a history of alcohol consumption had 2.2-fold higher
      median MDZ 1'-hydroxylation (P = 0.017), whereas no influence of age, gender, or
      smoking was evident. In conclusion, the investigated genetic factors did not
      contribute substantially to the large interindividual variability in midazolam
      hydroxylation, although alcohol consumption has a discernable but modest
      influence.

PMID- 16638819
TI  - Glutathione S-transferase omega 1 and omega 2 pharmacogenomics.
AB  - Glutathione S-transferase omega 1 and omega 2 (GSTO1 and GSTO2) catalyze
      monomethyl arsenate reduction, the rate-limiting reaction in arsenic
      biotransformation. As a step toward pharmacogenomic studies of these phase II
      enzymes, we resequenced human GSTO1 and GSTO2 using DNA samples from four ethnic
      groups. We identified 31 and 66 polymorphisms in GSTO1 and GSTO2, respectively,
      with four nonsynonymous-coding single nucleotide polymorphisms (cSNPs) in each
      gene. There were striking variations among ethnic groups in polymorphism
      frequencies and types. Expression constructs were created for all eight
      nonsynonymous cSNPs, as well as a deletion of codon 155 in GSTO1, and those
      constructs were used to transfect COS-1 cells. Quantitative Western blot
      analysis, after correction for transfection efficiency, showed a reduction in
      protein level of greater than 50% for the GSTO1 Tyr32 variant allozyme compared
      with wild type (WT), whereas levels for the Asp140, Lys208, Val236, and codon 155
      deletion variant constructs were similar to that of the WT. For GSTO2, the Tyr130
      and Ile158 variant allozymes showed 50 and 84% reductions in levels of
      expression, respectively, compared with WT, whereas the Ile41 and Asp142
      allozymes displayed levels similar to that of WT GSTO2. Rabbit reticulocyte
      lysate degradation studies showed that the GSTO1 Tyr32 and the GSTO2 Tyr130,
      Ile158, and Asp142/Ile158 variant allozymes were degraded more rapidly than were
      their respective WT allozymes. These observations raise the possibility of
      functionally significant pharmacogenomic variation in the expression and function
      of GSTO1 and GSTO2.

PMID- 16638820
TI  - Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1
      /- mouse islets.
AB  - Neural and endocrine factors (i.e., Ach and GLP-1) restore defective glucose
      stimulated insulin release in pancreatic islets lacking sulfonylurea type 1
      receptors (SUR1(-/-)) (Doliba NM, Qin W, Vatamaniuk MZ, Li C, Zelent D, Najafi H,
      Buettger CW, Collins HW, Carr RD, Magnuson MA, and Matschinsky FM. Am J Physiol
      Endocrinol Metab 286: E834-E843, 2004). The goal of the present study was to
      assess fuel-induced respiration in SUR1(-/-) islets and to correlate it with
      changes in intracellular Ca(2+), insulin, and glucagon secretion. By use of a
      method based on O(2) quenching of phosphorescence, the O(2) consumption rate
      (OCR) of isolated islets was measured online in a perifusion system. Basal
      insulin release (IR) was 7-10 times higher in SUR1(-/-) compared with control
      (CON) islets, but the OCR was comparable. The effect of high glucose (16.7 mM) on
      IR and OCR was markedly reduced in SUR1(-/-) islets compared with CON. Ach (0.5
      microM) in the presence of 16.7 mM glucose caused a large burst of IR in CON and
      SUR1(-/-) islets with minor changes in OCR in both groups of islets. In SUR1(-/-)
      islets, high glucose failed to inhibit glucagon secretion during stimulation with
      amino acids or Ach. We conclude that 1) reduced glucose responsiveness of SUR1(-/
      ) islets may be in part due to impaired energetics, as evidenced by significant
      decrease in glucose-stimulated OCR; 2) elevated intracellular Ca(2+) levels may
      contribute to altered insulin and glucagon secretion in SUR1(-/-) islets; and 3)
      The amplitudes of the changes in OCR during glucose and Ach stimulation do not
      correlate with IR in normal and SUR1(-/-) islets suggesting that the energy
      requirements for exocytosis are minor compared with other ATP-consuming
      reactions.

PMID- 16638821
TI  - Leucine in food mediates some of the postprandial rise in plasma leptin
      concentrations.
AB  - In vitro, leptin secretion is regulated at the level of mRNA translation by the
      rapamycin-sensitive mammalian target of rapamycin (mTOR) and its agonist leucine
      (Leu). Studies were conducted on meal-trained rats to evaluate the potential
      physiological relevance of these in vitro findings and the role of Leu in
      affecting rises in plasma leptin observed after a meal. In the first study, we
      correlated changes in plasma insulin and Leu to mTOR-signaling pathway activation
      and plasma leptin at different times during meal feeding. Rapid rises in plasma
      insulin and Leu, along with mTOR signaling (phosphorylation of eIF4G, S6K1, rpS6,
      and 4E-BP1) in adipose tissue were observed during the 3-h meal and declined
      thereafter. Plasma leptin rose more slowly, peaking at 3 h, and was inhibited by
      rapamycin (0.75 mg/kg) pretreatment. In another experiment, oral Leu or
      norleucine was provided instead of a meal. Leu and norleucine stimulated a rise
      in plasma leptin; however, the magnitude was less than the response to a complete
      meal. In a third study, rats were provided a meal that lacked Leu, branched-chain
      amino acids, or all amino acids. Stimulation of leptin secretion was reduced
      approximately 40% in animals provided the Leu-deficient meal. Further reductions
      were not observed by removing the other amino acids. Thus Leu appears to regulate
      most of the effects of dietary amino acids on the postprandial rise in plasma
      leptin but is responsible only for part of the leptin response to meal feeding.

PMID- 16638822
TI  - Targeted disruption of iNOS prevents LPS-induced S-nitrosation of IRbeta/IRS-1
      and Akt and insulin resistance in muscle of mice.
AB  - We have previously demonstrated that the insulin resistance associated with
      inducible nitric oxide synthase (iNOS) induction in two different models of
      obesity, diet-induced obesity and the ob/ob mice, is mediated by S-nitrosation of
      proteins involved in insulin signal transduction: insulin receptor beta-subunit
      (IRbeta), insulin receptor substrate 1(IRS-1), and Akt. S-nitrosation of IRbeta
      and Akt impairs their kinase activities, and S-nitrosation of IRS-1 reduces its
      tissue expression. In this study, we observed that LPS-induced insulin resistance
      in the muscle of wild-type mice, as demonstrated by reduced insulin-induced
      tyrosine phosphorylation of IRbeta and IRS-1, reduced IRS-1 expression and
      reduced insulin-induced serine phosphorylation of Akt. This resistance occurred
      in parallel with enhanced iNOS expression, which was accompanied by S-nitrosation
      of IRbeta/IRS-1 and Akt. In the muscle of iNOS(-/-) mice, we did not observe
      enhanced iNOS expression or any S-nitrosation of IRbeta/IRS-1 and Akt after LPS
      treatment. Moreover, insulin resistance was not present. The preservation of
      insulin-induced tyrosine phosphorylation of IRbeta and IRS-1, of IRS-1 protein
      expression, and of insulin-induced serine phosphorylation of Akt observed in LPS
      treated iNOS(-/-) mice strongly suggests that the insulin resistance induced by
      LPS is iNOS mediated, probably through S-nitrosation of proteins of early steps
      of insulin signaling.

PMID- 16638823
TI  - Metabolic programming: fetal origins of obesity and metabolic syndrome in the
      adult.
AB  - Exposure of the fetus to the intrauterine milieu can have profound effects on the
      health of the offspring in adulthood. Results of a series of studies demonstrate
      the powerful influence of the mother's metabolic state on whether the emerging
      adult develops obesity and hyperinsulinemia. Importantly, these attributes can be
      passed on to the next generation nongenetically and can be reversed and
      prevented.

PMID- 16638824
TI  - Mechanism of glucose intolerance in mice with dominant negative mutation of
      CEACAM1.
AB  - Mice with liver-specific overexpression of dominant negative phosphorylation
      defective S503A-CEACAM1 mutant (L-SACC1) developed chronic hyperinsulinemia
      resulting from blunted hepatic clearance of insulin, visceral obesity, and
      glucose intolerance. To determine the underlying mechanism of altered glucose
      homeostasis, a 2-h hyperinsulinemic euglycemic clamp was performed, and tissue
      specific glucose and lipid metabolism was assessed in awake L-SACC1 and wild-type
      mice. Inactivation of carcinoembryonic antigen-related cell adhesion molecule 1
      (CEACAM1) caused insulin resistance in liver that was mostly due to increased
      expression of fatty acid synthase and lipid metabolism, resulting in elevated
      intrahepatic levels of triglyceride and long-chain acyl-CoAs. Whole body insulin
      resistance in the L-SACC1 mice was further attributed to defects in insulin
      stimulated glucose uptake in skeletal muscle and adipose tissue. Insulin
      resistance in peripheral tissues was associated with significantly elevated
      intramuscular fat contents that may be secondary to increased whole body
      adiposity (assessed by (1)H-MRS) in the L-SACC1 mice. Overall, these results
      demonstrate that L-SACC1 is a mouse model in which chronic hyperinsulinemia acts
      as a cause, and not a consequence, of insulin resistance. Our findings further
      indicate the important role of CEACAM1 and hepatic insulin clearance in the
      pathogenesis of obesity and insulin resistance.

PMID- 16638825
TI  - Muscle-specific overexpression of wild type and R225Q mutant AMP-activated
      protein kinase gamma3-subunit differentially regulates glycogen accumulation.
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric complex that works as an
      energy sensor to integrate nutritional and hormonal signals. The naturally
      occurring R225Q mutation in the gamma3-subunit in pigs is associated with
      abnormally high glycogen content in skeletal muscle. Because skeletal muscle
      accounts for most of the body's glucose uptake, and gamma3 is specifically
      expressed in skeletal muscle, it is important to understand the underlying
      mechanism of this mutation in regulating glucose and glycogen metabolism. Using
      skeletal muscle-specific transgenic mice overexpressing wild type gamma3
      (WTgamma3) and R225Q mutant gamma3 (MUTgamma3), we show that both WTgamma3 and
      MUTgamma3 mice have 1.5- to 2-fold increases in muscle glycogen content. In
      WTgamma3 mice, increased glycogen content was associated with elevated total
      glycogen synthase activity and reduced glycogen phosphorylase activity, whereas
      alterations in activities of these enzymes could not explain elevated glycogen in
      MUTgamma3 mice. Basal, 5-aminoimidazole-AICAR- and phenformin-stimulated
      AMPKalpha2 isoform-specific activities were decreased only in MUTgamma3 mice.
      Basal rates of 2-DG glucose uptake were decreased in both WTgamma3 and MUTgamma3
      mice. However, AICAR- and phenformin-stimulated 2-DG glucose uptake were blunted
      only in MUTgamma3 mice. In conclusion, expression of either wild type or mutant
      gamma3-subunit of AMPK results in increased glycogen concentrations in muscle,
      but the mechanisms underlying this alteration appear to be different.
      Furthermore, mutation of the gamma3-subunit is associated with decreases in
      AMPKalpha2 isoform-specific activity and impairment in AICAR- and phenformin
      stimulated skeletal muscle glucose uptake.

PMID- 16638826
TI  - The mahoganoid mutation (Mgrn1md) improves insulin sensitivity in mice with
      mutations in the melanocortin signaling pathway independently of effects on
      adiposity.
AB  - Mahoganoid (Mgrn1(md)) is a mutation of the mahogunin (Mgrn1) gene. The
      hypomorphic allele suppresses the yellow pigmentation and obesity of the A(y)
      mouse that ubiquitously overexpresses agouti signaling protein (ASP). To assess
      the physiological effects of MGRN1 on energy and glucose homeostasis, we
      generated animals doubly mutant for Mgrn1(md) and A(y), Lep(ob), or a null allele
      of Mc4r, and diet-induced obesity (DIO) mice segregating for Mgrn1(md). Mgrn1(md)
      suppressed the obesity, hyperglycemia, and hyperinsulinemia of A(y) mice.
      Mgrn1(md) suppressed A(y)-induced obesity by reducing food intake, and reduced
      adiposity in Lep(ob)/Lep(ob) females, but did not alter the body weight or body
      composition of mice fed a high-fat diet. There was no effect of Mgrn1(md) on
      weight gain, body composition, energy intake, or energy expenditure in Mc4r-null
      animals. Mgrn1(md) reduced circulating insulin concentrations in DIO, A(y), and
      Mc4r-null but not Lep(ob)/Lep(ob) mice. The effect of Mgrn1(md) on circulating
      insulin concentrations was not due primarily to reductions in fat mass, since the
      plasma insulin concentrations of Mgrn1(md) mice segregating for either A(y) or
      Mc4r-null alleles, adjusted for fat mass and plasma glucose, were reduced
      compared with A(y) and Mc4r mice, respectively. The effect of Mgrn1(md) on
      insulin sensitivity of Mc4r-null mice suggests that Mgrn1(md) may be increasing
      insulin sensitivity via the hypothalamic melanocortin-3 receptor pathway.

PMID- 16638827
TI  - Nursing practice research and evidence-based practice.

PMID- 16638828
TI  - Being the next of kin of an adult person with muscular dystrophy.
AB  - A chronic disorder affects all members of the family in various ways. The aim of
      this study is to elucidate the next of kin's (N= 36) experiences when an adult
      family member has muscular dystrophy. The relationships were partner (36%, n=
      14), parent (18%, n= 7), child (21%, n= 8), sibling (15%, n= 6), and other
      relative (3%, n= 1). Latent content analysis is employed and involves an
      interpretation of the interviewtext. The results showthe meaning of being close
      to a person with muscular dystrophy through the themes that emerged: exposure of
      the family; the span between obligation and love; being vigilant, protective, and
      supportive; and striving for an ordinary life. This study reveals a need for
      healthcare staff to understand the next of kin's narrated meaning of changes when
      a family member has a progressive disease.

PMID- 16638829
TI  - Validating the utility of the Spanish version of the American Diabetes
      Association Risk Test.
AB  - The American Diabetes Association (ADA) Risk Test, often used for decisions to
      blood glucose screen or not, lacks studies reporting the reliability or validity
      for the Spanish version of the tool. The objective of this study is to further
      validate the utility of the Spanish version of the ADA's Risk Test for Latino
      Populations. A convenience sample of 316 Latinos participated in this study. A
      positive but weak statistical correlation was found between blood glucose and the
      Risk Test score (.138), suggesting low reliability and validity of the Spanish
      version of the instrument. Two internal consistency estimates of reliability
      techniques were computed for the Risk Test for diabetes scale items, indicating
      low reliability.

PMID- 16638830
TI  - The effectiveness of using a lipido-colloid dressing for patients with traumatic
      digital wounds.
AB  - This study compares the effect of a daily gauze dressing with that of a lipido
      colloid dressing on the time taken to make up the dressing and efficacy of the
      management of traumatic digital wounds. This is a randomized controlled trial of
      28 patients (16 experimental and 12 control) with injuries to their fingers and
      loss of tissue. The patients in the experimental and control groups were given a
      lipido-colloid dressing and a daily gauze dressing, respectively. The
      patients'wounds were assessed in terms of the size of the wound and the time it
      took for the wound to heal. The findings showed that patients in the experimental
      group had a faster recovery time from the healing of their wound than the control
      group (p= .024). The findings can help to establish an evidence-based practice in
      the management of traumatic digital wounds in clinical settings.

PMID- 16638831
TI  - Family members' perceptions of the quality of long-term care.
AB  - The aim of the study is to assess family members' perceptions of the quality of
      nursing care of older people and its relationships between demographic factors
      and family involvement. Data were gathered from family members of four
      residential homes (N= 474) using structured questionnaires. Data were analyzed
      using descriptive statistics, correlation, and predictive analyses. The results
      imply that family members' perceptions of quality were fairly positive. Age,
      educational background, and the frequency of visits on the ward were related with
      the quality perception. The association between quality perceptions and family
      involvement in care proved to be strong. The information and support from the
      staff and possibilities to participate in decision making were associated with
      high-quality ratings. The results demonstrate the need for formulating ward
      policies and training the nursing staff to allow increased family involvement and
      to support it in an appropriate way.

PMID- 16638832
TI  - Informal payments for health care: definitions, distinctions, and dilemmas.
AB  - There is increasing interest in the issue of informal payments for health care in
      low- and middle-income countries. Emerging evidence suggests that the phenomenon
      is both diverse, including many variants from cash payments to in-kind
      contributions and from gift giving to informal charging, and widespread, reported
      from countries in at least three continents. However, cross-national research is
      hampered by the lack of consensus among researchers on the definition of informal
      payments, and the definitions that have been proposed are unable to incorporate
      all forms of the phenomenon that have been described so far. This article aims to
      overcome this limitation by proposing a new definition based on the concept of
      entitlement for services. First, the various forms of informal payment observed
      in practice are reviewed briefly. Then, some of the proposed definitions are
      discussed, pointing out that none of the distinctive characteristics implied by
      these definitions, including illegality, informality, and corruption, is adequate
      to capture all varieties of the phenomenon. Next, an alternative definition is
      formulated, which identifies the distinctive feature common to all forms of
      informal payments as something that is contributed in addition to the terms of
      entitlement. Then, the boundaries implied by this definition are explored and,
      finally, the implications for research and policy making are discussed with
      reference to the lessons developed countries can learn from the experiences of
      transitional countries.

PMID- 16638833
TI  - Modeling eligibility under national systems of compensation for treatment injury.
AB  - How can different schemes of compensation for treatment injury be evaluated? This
      article offers an empirical approach to assessment based on the simulation of
      alternative models of eligibility using real-world data. It draws on information
      about adverse events generated from a representative survey of public hospital
      admissions in New Zealand and classifies these under a range of eligibility
      criteria for different possible compensation systems. These are then evaluated
      according to a number of policy design considerations, using variables available
      from the New Zealand study.

PMID- 16638834
TI  - The impact of state community benefit laws on the community health orientation
      and health promotion services of hospitals.
AB  - This study examined the effect of state community benefit laws and guidelines on
      the community health orientation and the provision of hospital-based health
      promotion services in hospitals. The sample included all not-for-profit and
      investor-owned acute-care hospitals in the United States during the year 2000.
      Multiple regression procedures were used to test the effect of community benefit
      laws and type of ownership while controlling for organizational and environmental
      variables. The results of these procedures indicated that, on average, not-for
      profit hospitals in the ten states with community benefit laws/guidelines
      reported significantly more community health orientation activities than did not
      for-profit hospitals in the forty other states. The results of the multiple
      regression procedures also indicated that, on average, the investor-owned
      hospitals in the ten states with laws/guidelines reported significantly more
      community health orientation activities than did the investor-owned hospitals in
      the forty other states. The study found that community benefit laws had the
      effect of decreasing ownership-related differences in reported community health
      orientation activities. Further, Levene's test of equality of variance showed
      that the not-for-profit hospitals in community benefit states exhibited
      significantly lower variance in the community health orientation activities when
      compared with the not-for-profit hospitals in non-community benefit states.
      However, none of the statistical tests supported the hypotheses that community
      benefit laws compelled or induced hospitals to offer significantly more health
      promotion services. The study concluded that coercive measures such as community
      benefit laws were effective in compelling not-for-profit hospitals to report
      increased community orientation activities, and it also concluded that the
      mimetic pressures associated with these laws were effective in inducing investor
      owned hospitals to report increased community orientation activities.

PMID- 16638837
TI  - The salience of tobacco in American politics.

PMID- 16638838
TI  - The role of law and politics in the formulation of tobacco policies.

PMID- 16638839
TI  - The problem of analyzing tobacco control as public policy is that it involves
      multilevel governance.

PMID- 16638840
TI  - Iron-related transcriptomic variations in CaCo-2 cells, an in vitro model of
      intestinal absorptive cells.
AB  - Regulation of iron absorption by duodenal enterocytes is essential for the
      maintenance of homeostasis by preventing iron deficiency or overload. Despite the
      identification of a number of genes implicated in iron absorption and its
      regulation, it is likely that further factors remain to be identified. For that
      purpose, we used a global transcriptomic approach, using the CaCo-2 cell line as
      an in vitro model of intestinal absorptive cells. Pangenomic screening for
      variations in gene expression correlating with intracellular iron content allowed
      us to identify 171 genes. One hundred nine of these genes are clustered into five
      types of expression profile. This is the first time that most of these genes have
      been associated with iron metabolism. Functional annotation of these five
      clusters indicates potential links between the immune response, proteolysis
      processes, and iron depletion. In contrast, iron overload is associated with
      cellular metabolism, especially that of lipids and glutathione involving redox
      function and electron transfer.

PMID- 16638841
TI  - Design of new benzoxazole-2-thione-derived inhibitors of Streptococcus pneumoniae
      hyaluronan lyase: structure of a complex with a 2-phenylindole.
AB  - The bacterial hyaluronan lyases (Hyals) that degrade hyaluronan, an important
      component of the extracellular matrix, are involved in microbial spread.
      Inhibitors of these enzymes are essential in investigation of the role of
      hyaluronan and Hyal in bacterial infections and constitute a new class of
      antibiotics against Hyal-producing bacteria. Recently, we identified 1,3
      diacetylbenzimidazole-2-thione and related molecules as inhibitors of
      streptococcal Hyal. One of such compounds, 1-decyl-2-(4-sulfamoyloxyphenyl)-1
      indol-6-yl sulfamate, was co-crystallized in a complex with Streptococcus
      pneumoniae Hyal and its structure elucidated. The resultant X-ray structure
      demonstrates that this inhibitor fits in the enzymatic active site via
      interactions resembling the binding mode of the natural hyaluronan substrate. X
      ray structural analysis also indicates binding interactions with the catalytic
      residues and those of a catalytically essential hydrophobic patch. An IC50 value
      of 11 microM for Hyal from Streptococcus agalactiae (strain 4755) qualifies this
      phenylindole compound as one of the most potent Hyal inhibitors known to date.
      The structural data suggested a similar binding mode for N-(3-phenylpropionyl)
      benzoxazole-2-thione. This new compound's inhibitory properties were confirmed
      resulting in discovery of yet another Hyal inhibitor (IC50 of 15 microM). These
      benzoxazole-2-thiones constitute a new class of inhibitors of bacterial Hyals and
      are well suited for further optimization of their selectivity, potency, and
      pharmacokinetic properties.

PMID- 16638842
TI  - Immunogenic cell death and cross-priming are reaching the clinical immunotherapy
      arena.

PMID- 16638843
TI  - Tumor necrosis factor-related apoptosis-inducing ligand pathway and its
      therapeutic implications.

PMID- 16638844
TI  - Alterations in the T-cell receptor variable beta gene-restricted profile of CD8+
      T lymphocytes in the peripheral circulation of patients with squamous cell
      carcinoma of the head and neck.
AB  - PURPOSE: Apoptosis of activated CD8(+) T cells is often seen in tumor
      infiltrating lymphocytes and circulating peripheral blood mononuclear cells
      (PBMC) in patients with squamous cell carcinoma of the head and neck (SCCHN). We
      investigated whether T-cell receptor (TCR) variable beta chain (Vbeta)-restricted
      T cells were more sensitive to apoptosis than non-TCR Vbeta-restricted T cells.
      EXPERIMENTAL DESIGN: Flow cytometry analysis with anti-TCR Vbeta antibodies was
      used to define expansions and contractions of Vbeta-restricted T cells in
      patients with SCCHN relative to normal donors. This staining was combined with
      Annexin V binding to indicate early T-cell apoptosis. RESULTS: The TCR Vbeta
      profiles of CD3(+) T cells in tumor-infiltrating lymphocytes and PBMCs of
      patients with SCCHN were altered relative to controls, with one to five
      expansions and numerous contractions of TCR Vbeta-restricted T cells detected.
      These types of alterations were significantly greater in CD8(+) than CD4(+) T
      cells. Enhanced Annexin V binding to CD8(+) T cells was evident in PBMCs obtained
      from all patients, with 3 of 13 showing preferential targeting for apoptosis of
      TCR Vbeta-restricted T cells. CONCLUSIONS: TCR Vbeta profiles of CD8(+) T cells
      were altered in patients with SCCHN relative to normal controls. This may reflect
      increased apoptosis of expanded or contracted CD8(+) T cells, which define the
      TCR Vbeta profile of antigen-responsive T-cell populations in patients with
      cancer.

PMID- 16638845
TI  - Transcriptional and posttranscriptional down-regulation of the imprinted tumor
      suppressor gene ARHI (DRAS3) in ovarian cancer.
AB  - PURPOSE: ARHI expression is lost or markedly down-regulated in the majority of
      ovarian cancers. The mechanism by which ARHI is down-regulated in ovarian cancers
      is still not clear. Our previous reports indicated that ARHI promoter activity
      was reduced in ovarian cancer cells, due in part to the effects of negative
      regulatory transcription factor(s). EXPERIMENTAL DESIGN AND RESULTS: We now show
      that E2F1 and E2F4, but not E2F2, E2F3, or E2F5, bind to the ARHI promoter and
      repress its activity in ovarian cancer cells. Consistent with this observation,
      immunochemical staining of cell lines and of 364 samples of ovarian cancer tissue
      show that the expression of E2F1 and E2F4 proteins is much higher in ovarian
      cancer cells than in normal ovarian epithelial cells, and that increased
      expression of E2Fs was negatively correlated with ARHI expression (P < 0.05).
      Mutation of the putative E2F binding site in the ARHI promoter reversed this
      inhibitory effect and significantly increased ARHI promoter activity. In addition
      to the effects of transcriptional regulation, ARHI mRNA also exhibited a
      significantly reduced half-life in ovarian cancer cells when compared with that
      in normal ovarian epithelial cells (P < 0.01), suggesting posttranscriptional
      regulation of ARHI expression. ARHI mRNA contains AU-rich elements (ARE) in the
      3'-untranslated region. We have found that these AREs interact with HuR, an ARE
      binding protein that stabilizes bound mRNAs, possibly contributing to the rapid
      turnover of ARHI mRNA. Finally, reduced HuR ARE binding activity was observed in
      ovarian cancer cells when compared with normal ovarian surface epithelium.
      CONCLUSIONS: Taken together, our data suggest that ARHI expression is regulated
      at both the transcriptional and the posttranscriptional levels, contributing to
      the dramatic decrease in ARHI expression in ovarian cancers.

PMID- 16638846
TI  - Molecular evidence for the same clonal origin of multifocal papillary thyroid
      carcinomas.
AB  - PURPOSE: Patients with papillary thyroid carcinoma often have two or more
      distinct papillary tumors at thyroidectomy. Whether these multifocal papillary
      lesions are clonally related or whether they arise independently is unknown as
      previous studies have shown conflicting results. Molecular analysis of
      microsatellite alterations and X-chromosome inactivation status in separate
      tumors from the same patient can be used to define the genetic relationships
      among the multiple coexisting tumors. EXPERIMENTAL DESIGN: We examined 64
      separate tumors from 22 female patients who underwent thyroidectomy for thyroid
      carcinoma. All patients had multiple and separate papillary carcinomas (range,
      two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin
      embedded tissue sections using laser-capture microdissection. Loss of
      heterozygosity assays for three microsatellite polymorphic markers for putative
      tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22
      p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done
      on the tumors from all patients. RESULTS: Twenty of 22 (91%) cases showed allelic
      loss in one or more of the papillary lesions in at least one of the three
      polymorphic markers analyzed. Concordant allelic loss patterns between coexisting
      papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of
      nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions
      was seen in all informative cases. CONCLUSION: Our data suggest that the
      multifocal tumors in patients with papillary thyroid carcinoma often arise from
      the same clone. Thus, intrathryoid metastasis may play an important role in the
      spread of papillary thyroid carcinoma, a finding that has important therapeutic,
      diagnostic, and prognostic implications.

PMID- 16638847
TI  - Establishment of perineural invasion models and analysis of gene expression
      revealed an invariant chain (CD74) as a possible molecule involved in perineural
      invasion in pancreatic cancer.
AB  - PURPOSE: Perineural invasion causes frequent local recurrence even after
      resection and a poor prognosis for pancreatic cancer. We established perineural
      invasion models and analyzed the molecular mechanism of perineural invasion in
      pancreatic cancer. EXPERIMENTAL DESIGN: Seven pancreatic cancer cell lines with
      or without human peripheral nerves were s.c. implanted in nonobese
      diabetes/severe combined immunodeficient mice. We compared expression profiles
      among high and low perineural invasion cell lines by using an oligonucleotide
      microarray. We examined up-regulation of the invariant chain (CD74) in high
      perineural invasion cell lines in mRNA and protein levels and surgical cases
      immunohistochemically. RESULTS: Four of seven pancreatic cancer cell lines
      (CaPan1, CaPan2, CFPAC, and MPanc96) showed perineural invasion to s.c.
      transplanted human peripheral nerves. Moreover, CaPan1 and CaPan2 (high
      perineural invasion group) also resulted in a high frequency of perineural
      invasion to mouse s.c. peripheral nerves, whereas three pancreatic cancer cell
      lines HPAFII, AsPC1, and Panc1 (low perineural invasion group) did not show
      perineural invasion to either human or mouse nerves. We identified 37 up
      regulated genes and 12 down-regulated genes in the high perineural invasion group
      compared with the low perineural invasion group. Among them, CD74 was up
      regulated in the high perineural invasion group in mRNA and protein levels.
      Furthermore, immunohistochemical expression of CD74 in clinical cases revealed
      its significant overexpression in pancreatic cancer with perineural invasion (P <
      0.008). CONCLUSIONS: This is the first report of perineural invasion models using
      human pancreatic cancer cell lines. In combination with gene expression
      profiling, it was indicated that CD74 could be a candidate molecule involved in
      perineural invasion. These models provide new approaches for study of perineural
      invasion in pancreatic cancer.

PMID- 16638848
TI  - Human melanoma metastases express functional CXCR4.
AB  - PURPOSE: The chemokine receptor CXCR4 was identified as an independent predictor
      of poor prognosis in primary melanoma. The aim of the study was to investigate
      the role of CXCR4 in human melanoma metastases. EXPERIMENTAL DESIGN: CXCR4
      expression was evaluated in melanoma metastases and in metastatic cell lines
      through immunohistochemistry, immunoblotting, immunofluorescence, and reverse
      transcription-PCR. The function of CXCR4 was tested in the presence of the
      ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and 
      2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration
      capabilities. RESULTS: CXCR4 expression was detected in 33 out of 63 (52.4%)
      metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed
      cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels
      of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell
      lines showed low to moderate degrees of expression (5-65% of positive cells).
      Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell
      lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically
      inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43,
      and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions;
      AMD3100 (1 mumol/L) inhibited the spontaneous and CXCL12-induced proliferation.
      No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate
      toward CXCL12. CONCLUSIONS: These findings indicate that CXCR4 is expressed and
      active in human melanoma metastases, suggesting that active inhibitors such as
      AMD3100 may be experienced in human melanoma.

PMID- 16638849
TI  - Identification of a set of seven genes for the monitoring of minimal residual
      disease in pediatric acute myeloid leukemia.
AB  - BACKGROUND: Monitoring of minimal residual disease (MRD) has become a strong
      diagnostic tool in acute lymphoblastic leukemia. It is used for risk-adapted
      therapy and for the recognition of pending relapses. In acute myeloid leukemia
      (AML), there is still a need for more suitable MRD markers. EXPERIMENTAL DESIGN:
      A stepwise approach which combined genome-wide expression profiling, TaqMan low
      density arrays, and a TaqMan real-time PCR-based screening was used to identify
      new markers for the monitoring of MRD in AML. Leukemic cells from 52 children
      with AML and 145 follow-up samples from 25 patients were analyzed. RESULTS: Seven
      genes were identified which are vastly overexpressed in many patients with AML
      compared with healthy bone marrow: CCL23, GAGED2, MSLN, SPAG6, and ST18 as well
      as the previously described markers WT1 and PRAME. The expression of all genes
      decreased to normal levels in patients who achieved a continuous complete
      remission. Elevated levels of at least one gene were found prior to relapse in 7
      out of 10 patients who relapsed. CONCLUSIONS: This set of genes should allow a
      sensitive and specific monitoring of MRD in AML. Notably, some of these markers
      could also serve as therapeutic targets or might be involved in leukemogenesis.
      MSLN is already used as a target for immunotherapy in clinical trials in other
      malignancies.

PMID- 16638850
TI  - Expression of KLF5 is a prognostic factor for disease-free survival and overall
      survival in patients with breast cancer.
AB  - PURPOSE: Kruppel-like factor (KLF5) is a cell growth mediator in various
      epithelial cells. Higher KLF5 increases cell growth rate and leads to transformed
      phenotypes. Because tumor cell proliferation is tightly associated with tumor
      progression, and consequently, with survival of cancer patients, we wanted to
      examine the prognostic value of KLF5 gene expression for patients with breast
      cancer. EXPERIMENTAL DESIGN: The gene expression levels of KLF5, ER, PR, HER2,
      and MKI67 were quantified in the tumor tissues of 90 patients with breast cancer
      and correlated with disease-free survival and overall survival of the patients.
      The correlations of gene expression between KLF5 and ER, PR, HER2, and MKI67 were
      analyzed. In addition, KLF5 expression was also compared with clinical data and
      age of patients. RESULTS: Statistically significant correlations were found
      between gene expression of KLF5 and both disease-free survival (univariate
      analysis) and overall survival (univariate and multivariate analysis). Patients
      with higher KLF5 expression had shorter disease-free survival and overall
      survival time, whereas patients with lower KLF5 expression had better survival.
      Moreover, KLF5 was also found to be positively correlated with HER2 and MKI67,
      and negatively correlated with age of the patients at diagnosis. CONCLUSION: The
      gene expression of KLF5 is directly correlated with cell proliferation in vivo
      and is a prognostic factor for patients with breast cancer. Patients with higher
      KLF5 expression have shorter disease-free survival and overall survival than
      patients with lower KLF5 expression. In addition, KLF5 has higher expression in
      patients ages </=50 years old than in patients >50 years old.

PMID- 16638851
TI  - Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family
      verproline-homologous protein 2 in adenocarcinoma of the lung.
AB  - PURPOSE: Highly invasive and metastatic cancer cells, such as adenocarcinoma of
      the lung cells, form irregular protrusions by assembling a branched network of
      actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3)
      complex initiates actin assembly to form lamellipodial protrusions by binding to
      Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2
      (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the
      lung was investigated to elucidate its prognostic value. EXPERIMENTAL DESIGN:
      Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115
      adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan
      Meier disease-free survival and overall survival curves were analyzed to
      determine the prognostic significance of the coexpression of Arp2 and WAVE2.
      RESULTS: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer
      cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer
      cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph
      node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar
      carcinomas (P < 0.0001). The patients whose cancer cells coexpressed them had a
      shorter disease-free survival time (P < 0.0001) and overall survival time (P <
      0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2
      and WAVE2 is an independent risk factor for tumor recurrence. CONCLUSIONS:
      Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may
      be involved in the mechanism of cancer metastasis.

PMID- 16638852
TI  - High-resolution mapping of tumor redox status by magnetic resonance imaging using
      nitroxides as redox-sensitive contrast agents.
AB  - PURPOSE: There is considerable research directed toward the identification and
      development of functional contrast agents for medical imaging that superimpose
      tissue biochemical/molecular information with anatomical structures. Nitroxide
      radicals were identified as in vivo radioprotectors. Being paramagnetic, they can
      provide image contrast in magnetic resonance imaging (MRI) and electron
      paramagnetic resonance imaging (EPRI). The present study sought to determine the
      efficacy of nitroxide radioprotectors as functional image contrast agents.
      EXPERIMENTAL DESIGN: Nitroxide radioprotectors, which act as contrast agents,
      were tested by EPRI and MRI to provide tissue redox status information
      noninvasively. RESULTS: Phantom studies showed that the nitroxide, 3-carbamoyl
      PROXYL (3CP), undergoes time-dependent reduction to the corresponding diamagnetic
      hydroxylamine only in the presence of reducing agents. The reduction rates of 3CP
      obtained by EPRI and MRI were in agreement suggesting the feasibility of using
      MRI to monitor nitroxide levels in tissues. The levels of 3CP were examined by
      EPRI and MRI for differences in reduction between muscle and tumor (squamous cell
      carcinoma) implanted in the hind leg of C3H mice simultaneously. In vivo
      experiments showed a T1-dependent image intensity enhancement afforded by 3CP
      which decreased in a time-dependent manner. Reduction of 3CP was found to be the
      dominant mechanism of contrast loss. The tumor regions exhibited a faster decay
      rate of the nitroxide compared to muscle (0.097 min(-1) versus 0.067 min(-1),
      respectively). CONCLUSIONS: This study shows that MRI can be successfully used to
      co-register tissue redox status along with anatomic images, thus providing
      potentially valuable biochemical information from the region of interest.

PMID- 16638853
TI  - Measuring tissue-based biomarkers by immunochromatography coupled with reverse
      phase lysate microarray.
AB  - PURPOSE: There is a need for new technologies to study tissue-based biomarkers.
      The current gold standard, immunohistochemistry, is compromised by variability in
      tissue processing and observer bias. Reverse transcription-PCR (RT-PCR),
      immunocytochemistry, and reverse-phase lysate microarrays (RPM) are promising
      alternative technologies but have not yet been validated, or correlated, on the
      same patient-derived tissues. Furthermore, RPM is currently limited by time
      consuming microdissection and low amounts of evaluable protein lysates.
      EXPERIMENTAL DESIGN: Metastatic melanoma was surgically excised from 30 patients
      and macroscopically dissected from surrounding stroma. Each specimen was
      processed by formalin-fixation (immunohistochemistry), cytospin
      (immunocytochemistry), or disaggreagation and enrichment (RT-PCR and RPM). The
      latter protocol uses immunochromatography to remove hematopoetic-derived cells,
      thus enriching for melanoma cells. Each sample was measured for the expression of
      gp100 or MART-1 normalized to actin. RESULTS: Immunochromatography coupled with
      RPM (I-RPM) is reproducible (r >/= 0.70) and, for gp100, correlates strongly with
      immunohistochemistry and immunocytochemistry (r = 0.78 and 0.76, respectively)
      and moderately with transcript levels, measured by RT-PCR (r = 0.61). In
      contrast, for MART-1, I-RPM correlates strongly with transcript level (r = 0.78)
      but only moderately strong correlations are noted with immunohistochemistry and
      immunocytochemistry (r = 0.64 and 0.59, respectively). In general, transcript
      levels show only moderately strong correlations with immunohistochemistry and
      immunocytochemistry (r = 0.41-0.64). CONCLUSION: I-RPM is a promising technology
      for quantitative grading of tissue biomarkers; however, antigen-dependent
      correlations are noted.

PMID- 16638854
TI  - Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham
      Prognostic Index.
AB  - PURPOSE: Prognostication of breast cancer using clinicopathologic variables,
      although useful, remains imperfect. Many reports suggest that gene expression
      profiling can refine the current approach. Alternatively, it has been shown that
      panels of proteins assessed by immunohistochemistry might also be useful in this
      regard. We evaluate the prognostic potential of a panel of markers by
      immunohistochemistry in a large case series to establish if either a single
      marker or a panel could improve the prognostic power of the Nottingham Prognostic
      Index (NPI). We validated the results in an independent series. EXPERIMENTAL
      DESIGN AND RESULTS: The expression of 13 biomarkers was evaluated in 930 breast
      cancers on a tissue microarray. Eight markers [estrogen receptor (ER),
      progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and
      HER2] showed a significant association with survival at 10 years on univariate
      analysis. On multivariate analysis that included these eight markers and the NPI,
      only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16
      1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR,
      0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent
      multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62;
      95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16
      1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful
      than the use of a panel of markers. Based on these results, an independent series
      was used to validate the prognostic significance of Bcl-2. ER and PR were also
      evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P =
      0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI,
      1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years.
      CONCLUSION: Bcl-2 is an independent predictor of breast cancer outcome and seems
      to be useful as a prognostic adjunct to the NPI, particularly in the first 5
      years after diagnosis.

PMID- 16638855
TI  - Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical
      cancer is associated with poor disease outcome.
AB  - PURPOSE: The pp125 focal adhesion kinase (FAK) plays a pivotal role in tumor cell
      signaling. FAK expression has been linked to tumor cell invasion and metastasis,
      but data on cervical cancer are inconclusive. Our goal was to investigate FAK
      expression in cervical cancer and to assess whether its expression correlates
      with prognosis. EXPERIMENTAL DESIGN: FAK expression was examined using
      immunohistochemistry with sections from 162 resected cervical cancer specimens.
      Kaplan-Meier survival curves were used to determine the significance of FAK
      expression in the prognosis of cervical cancer patients. RESULTS: Specific FAK
      expression was found in the tumor cells, whereas normal cervical epithelium
      showed barely any FAK expression. Of 162 invasive cervical cancer specimens, 55
      (34%) revealed weak expression of FAK, whereas moderate and strong expression was
      found in 63 (39%) and 44 (27%) tumors, respectively. Patients with tumors
      expressing weak amounts of FAK were characterized by a significantly poorer
      overall survival compared with those with moderate and high intratumoral FAK
      expression (P = 0.002). Weak expression of FAK correlated with pelvic lymph node
      metastasis (P = 0.026) and recurrent disease (P = 0.013). Multivariate Cox
      regression analysis revealed decreased FAK expression and pelvic lymph node
      metastasis to be significant independent factors predictive of poor disease
      outcome (hazard ratio, 0.36; P = 0.005; hazard ratio, 2.38; P = 0.018,
      respectively). CONCLUSIONS: Weak expression of FAK in invasive cervical cancer is
      a strong independent predictor of poor patient outcome. Further studies are
      warranted to elucidate whether FAK expression analysis is a suitable tool
      identifying patients at high risk even at an early clinical stage.

PMID- 16638856
TI  - A combination of molecular markers accurately detects lymph node metastasis in
      non-small cell lung cancer patients.
AB  - Occult lymph node metastasis (micrometastasis) is a good prognostic indicator in
      non-small cell lung cancer (NSCLC) and could be used to direct adjuvant
      chemotherapy in stage I patients. This study was designed to evaluate molecular
      markers for detection of occult lymph node metastasis in NSCLC, define the best
      marker or marker combination to distinguish positive from benign lymph nodes, and
      evaluate these markers in lymph nodes from pathologically node-negative (pN(0))
      NSCLC patients. Potential markers were identified through literature and database
      searches and all markers were analyzed by quantitative reverse transcription-PCR
      in a primary screen of six NSCLC specimens and 10 benign nodes. Selected markers
      were further evaluated on 21 primary NSCLC specimens, 21 positive nodes, and 21
      benign nodes, and the best individual markers and combinations were identified. A
      combination of three markers was further validated on an independent set of 32
      benign lymph nodes, 38 histologically positive lymph nodes, and 462 lymph nodes
      from 68 pN(0) NSCLC patients. Forty-two markers were evaluated in the primary
      screen and eight promising markers were selected for further analysis. A
      combination of three markers (SFTPB, TACSTD1, and PVA) was identified that
      provided perfect classification of benign and positive nodes in all sample sets.
      PVA and SFTPB are particularly powerful in tumors of squamous and adenocarcinoma
      histologies, respectively, whereas TACSTD1 is a good general marker for NSCLC
      metastasis. The combination of these genes identified 32 of 462 (7%) lymph nodes
      from 20 of 68 (29%) patients as potentially positive for occult metastasis. Long
      term follow-up will determine the clinical relevance of these findings.

PMID- 16638857
TI  - Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic
      cancer: relationship to molecular mechanisms of gemcitabine resistance and
      survival.
AB  - Gemcitabine is considered the standard first-line therapy for patients with
      advanced pancreatic cancer. More recent strategies have focused on improving the
      efficacy of gemcitabine by either improving the method of delivery or by
      combining gemcitabine with other non-cross-resistant chemotherapy agents or with
      small-molecule drugs. However, the clinical benefits, response rates, and
      duration of responses have been modest. Deoxycytidine kinase (dCK) is the rate
      limiting enzyme involved in the metabolism of gemcitabine. The expression of dCK
      has been postulated to be correlative of gemcitabine resistance. We determined
      the relationship of dCK immunohistochemical protein expression and/or genetic
      status of dCK in a panel of human pancreatic cancer tissues and pancreatic cancer
      cell lines and determined the relationship of these variables to the clinical
      outcome of patients treated with gemcitabine. We report that dCK protein
      expression is expressed in the majority of pancreatic cancers analyzed (40 of 44
      cases, 91%) and showed a range of labeling intensities ranging from 1+ (labeling
      weaker in intensity than normal lymphocytes present in same section) to 3+
      (labeling greater in intensity than normal lymphocytes present in same section).
      When labeling intensity was compared with survival, low dCK expression (1+
      labeling) was correlated with both overall survival (P < 0.009) and progression
      free survival following gemcitabine treatment (P < 0.04). Low dCK labeling
      intensity was also significantly correlated with patient age (70.3 +/- 8.1 versus
      59.8 +/- 7.4 years; P < 0.0006), suggesting that age-related methylation of the
      dCK gene may account in part for the observed differences. Sequencing of the
      entire dCK coding sequence in 17 cell lines and 9 patients' cancer tissues with
      disease progression while on gemcitabine did not identify any mutations,
      suggesting that genetic alterations of dCK are not a common mechanism of
      resistance to gemcitabine for this tumor type. Moreover, dCK labeling showed
      similar patterns and intensities of labeling among matched pretreatment and post
      treatment tissues. In summary, pretreatment levels of dCK protein are most
      correlated with overall survival following gemcitabine treatment and are stable
      even after resistance to gemcitabine is clinically documented.

PMID- 16638858
TI  - The diagnostic accuracy of reverse transcription-PCR quantification of
      cytokeratin mRNA in the detection of sentinel lymph node invasion in oral and
      oropharyngeal squamous cell carcinoma: a comparison with immunohistochemistry.
AB  - PURPOSE: The main goal of sentinel lymph node (SLN) detection in head and neck
      squamous cell carcinomas is to limit neck dissections to pN+ cases only. However,
      intraoperative + diagnosis cannot be routinely done using the current gold
      standard, serial step sectioning with immunohistochemistry. Real-time
      quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with
      intraoperative use, proving highly sensitive in detecting molecular markers. This
      study postoperatively assessed the accuracy of quantitative RT-PCR in staging
      patients from their SLN. EXPERIMENTAL DESIGN: A combined analysis on the same SLN
      by serial step sectioning with immunohistochemistry and quantitative RT-PCR
      targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with
      oral or oropharyngeal squamous cell carcinoma and 10 control subjects. RESULTS:
      From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size
      for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89,
      0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology
      positive SLNs (macro- and micrometastases) showed higher mRNA values than
      negative SLNs for KRT 17 (P < 10(-4)) and KRT 14 (P < 10(-2)). KRT 5 showed
      nonsignificant results. KRT 17 seemed to be the most accurate marker for the
      diagnosis of micrometastases of a size >450 mum. Smaller micrometastases and
      isolated tumor cells did not provide results above the background level. Receiver
      operating characteristic curve analysis for KRT 17 identified a cutoff value
      where patient staging reached 100% specificity and sensitivity for macro- and
      micrometastases. CONCLUSION: Quantitative RT-PCR for SLN staging in cN(0)
      patients with oral and oropharyngeal squamous cell carcinoma seems to be a
      promising approach.

PMID- 16638859
TI  - N-acetylglucosaminyltransferase V and beta1-6 branching N-linked oligosaccharides
      are associated with good prognosis of patients with bladder cancer.
AB  - PURPOSE: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes
      beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked
      oligosaccharides (N-glycan) of cell proteins. We examined the relationship
      between GnT-V expression and clinicopathologic features of the patients with
      bladder cancer. EXPERIMENTAL DESIGN: We immunohistochemically examined GnT-V
      expression in paraffin-embedded bladder cancer specimen using anti-GnT-V
      monoclonal antibody. We compared GnT-V expression with cause-specific survival of
      the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier
      survival curves were generated to show the cause-specific survival. Univariate
      and multivariate analyses were carried out to compare GnT-V expression with other
      clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and
      N-linked oligosaccharide structure in bladder cancer specimens. RESULTS:
      Immunohistochemistry revealed that GnT-V expression inversely correlated with
      tumor grade and stage. The incidence of positive GnT-V expression in bladder
      cancer was significantly higher in low-grade/superficial cancer than in high
      grade/invasive cancer. The patients whose tumor was positive for GnT-V survived
      significantly longer than those whose tumor was negative for GnT-V. Univariate
      and multivariate analyses revealed that GnT-V expression was an independent
      predictor of prognosis of the patient. The expression of GnT-V mRNA determined by
      reverse transcription-PCR was consistent with the results with
      immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed
      that superficial bladder cancer is rich in branched N-linked oligosaccharides,
      for which biosynthesis GnT-V is responsible. CONCLUSIONS: GnT-V and its resultant
      beta1-6 branching N-linked oligosaccharides are closely related to low malignant
      potential and good prognosis of the patients with bladder cancer.

PMID- 16638860
TI  - Reduced plasma RNA integrity in nasopharyngeal carcinoma patients.
AB  - PURPOSE: Recent research has shown the feasibility of detecting cell-free RNA
      markers in human subjects. As elevated RNase activity has previously been
      described in the circulation of cancer patients, we hypothesized that cancer
      patients may have reduced plasma RNA integrity. In this study, we used
      nasopharyngeal carcinoma (NPC) as a model system to test this hypothesis.
      EXPERIMENTAL DESIGN: Plasma RNA integrity was determined using the ratio of the
      concentrations of transcript sequences corresponding to the 3' to those from the
      5' end of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
      Transcript concentrations were measured using real-time quantitative reverse
      transcription-PCR assays targeting the 5' and 3' regions. We analyzed the plasma
      RNA integrity in 49 untreated NPC patients and 53 healthy controls. We also
      assessed the plasma samples from 19 NPC patients before and after radiotherapy to
      further show the clinical potential of this marker. RESULTS: The 3' to 5' GAPDH
      ratio was significantly lower in the plasma of untreated NPC patients when
      compared with healthy controls (0.0252 versus 0.0485, P = 0.024). Statistical
      analysis showed that plasma GAPDH ratio was correlated with tumor stage but not
      with sex and age. Moreover, 14 of 19 NPC patients (74%) showed significant
      increase in the plasma GAPDH ratio following radiotherapy (P = 0.003). All of
      these patients were in clinical remission after treatment. CONCLUSIONS: Our
      findings suggest that NPC is associated with disturbances in the integrity of
      cell-free circulating RNA, raising the possibility that measurement of plasma RNA
      integrity may serve as a useful marker for the diagnosis and monitoring of
      malignant diseases.

PMID- 16638861
TI  - A phase II trial of intraperitoneal photodynamic therapy for patients with
      peritoneal carcinomatosis and sarcomatosis.
AB  - PURPOSE: A previous phase I trial of i.p. photodynamic therapy established the
      maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated
      photodynamic therapy and showed encouraging efficacy. The primary objectives of
      this phase II study were to determine the efficacy and toxicities of i.p.
      photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis.
      EXPERIMENTAL DESIGN: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before
      debulking surgery. Intraoperative laser light was delivered to the peritoneal
      surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete
      response, (b) failure-free survival time, and (c) overall survival time.
      Photosensitizer levels in tumor and normal tissues were measured. RESULTS: One
      hundred patients were enrolled into one of three strata (33 ovarian, 37
      gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light
      treatment. All 100 patients had progressed by the time of statistical analysis.
      The median failure-free survival and overall survival by strata were ovarian, 2.1
      and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and
      21.9 months. Substantial fluid shifts were observed postoperatively, and the
      major toxicities were related to volume overload. Two patients died in the
      immediate postoperative period from bleeding, sepsis, adult respiratory distress
      syndrome, and cardiac ischemia. CONCLUSIONS: Intraperitoneal Photofrin-mediated
      photodynamic therapy is feasible but does not lead to significant objective
      complete responses or long-term tumor control. Heterogeneity in photosensitizer
      uptake and tumor oxygenation, lack of tumor specificity for photosensitizer
      uptake, and the heterogeneity in tissue optical properties may account for the
      lack of efficacy observed.

PMID- 16638862
TI  - Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines
      for the treatment of patients with metastatic melanoma.
AB  - PURPOSE: Two clinical trials were conducted to evaluate the clinical efficacy and
      immunologic impact of vaccination against the tyrosinase protein plus systemic
      interleukin 2 (IL-2) administration in patients with advanced metastatic
      melanoma. EXPERIMENTAL DESIGN: Full-length tyrosinase was employed as an
      immunogen to induce diverse immunologic responses against a commonly expressed
      melanoma antigen. Heterologous prime/boost vaccination with recombinant vaccinia
      and fowlpox vectors encoding tyrosinase was first explored in a randomized three
      arm phase II trial, in which vaccines were administered alone or concurrently
      with low-dose or high-dose IL-2. In a subsequent single cohort phase II trial,
      all patients received the same vaccines and high-dose IL-2 sequentially rather
      than concurrently. RESULTS: Among a total of 64 patients treated on these trials,
      8 objective partial responses (12.5%) were observed, all in patients receiving
      high-dose IL-2. Additional patients showed evidence of lesional regression (mixed
      tumor response) or overall regression that did not achieve partial response
      status (minor response). In vitro evidence of enhanced immunity against
      tyrosinase following protocol treatments was documented in 3 of 49 (6%) patients
      tested serologically, 3 of 23 (13%) patients tested for T-cell recognition of
      individual tyrosinase peptides, and 4 of 16 (25%) patients tested for T-cell
      recognition of full-length tyrosinase protein with real-time reverse
      transcription-PCR techniques. CONCLUSIONS: Whereas prime/boost immunization with
      recombinant vaccinia and fowlpox viruses enhanced antityrosinase immunity in some
      patients with metastatic melanoma, it was ineffective alone in mediating clinical
      benefit, and in combination with IL-2 did not mediate clinical benefit
      significantly different from that expected from treatment with IL-2 alone.

PMID- 16638863
TI  - Optimization of patient selection for gefitinib in non-small cell lung cancer by
      combined analysis of epidermal growth factor receptor mutation, K-ras mutation,
      and Akt phosphorylation.
AB  - PURPOSE: Mutations in epidermal growth factor receptor (EGFR) are strongly
      predictive of gefitinib efficacy in non-small-cell lung cancer. However, the
      presence of EGFR mutant nonresponses and nonmutant responses points out the need
      for more comprehensive analysis. PATIENTS AND METHODS: For 69 non-small-cell lung
      cancer patients treated with gefitinib, we have extended our analysis to EGFR
      gene copy number by fluorescence in situ hybridization, mutations in K-ras, HER2,
      and exon 20 of EGFR by direct sequencing, and phosphatase and tensin homologue
      expression by immunohistochemistry, in addition to EGFR exons 18, 19, and 21, and
      phosphorylations of Akt and extracellular signal-regulated kinase reported
      previously. RESULTS: EGFR mutation and high gene copy number were associated with
      better objective response in univariate analysis. However, only gefitinib
      sensitive EGFR mutation was independently predictive of both response (P = 0.011)
      and survival (P = 0.002) in multivariate analysis. No patients with K-ras
      mutation, including two EGFR mutants, showed response. In EGFR nonmutants,
      patients with either K-ras mutation or p-Akt overexpression exhibited poor
      response and time-to-progression whereas patients with high gene copy number
      tended to have better outcomes in univariate analysis. In multivariate analysis
      of time-to-progression in EGFR nonmutants, K-ras mutation or p-Akt overexpression
      was associated with shorter time-to-progression (P = 0.017). No patient with HER2
      mutation showed response to gefitinib. Reduced phosphatase and tensin homologue
      expression was not associated with gefitinib sensitivity. CONCLUSION: Gefitinib
      sensitive EGFR mutation is the single most important predictor of gefitinib
      sensitivity. In addition to EGFR mutation, K-ras mutation and Akt phosphorylation
      aid in better prediction of gefitinib responsiveness in non-small-cell lung
      cancer.

PMID- 16638864
TI  - Association of DNA repair and steroid metabolism gene polymorphisms with clinical
      late toxicity in patients treated with conformal radiotherapy for prostate
      cancer.
AB  - OBJECTIVE: To explore the possible relationship between single nucleotide
      polymorphisms (SNP) in candidate genes encoding DNA damage
      recognition/repair/response and steroid metabolism proteins with respect to
      clinical radiation toxicity in a retrospective cohort of patients previously
      treated with three-dimensional conformal radiotherapy (3-DCRT) for prostate
      cancer. EXPERIMENTAL DESIGN: One hundred twenty-four patients with prostate
      cancer underwent 3-DCRT at our institution between September 1996 and December
      2000. Of these, 83 consented for follow-up of blood sampling and SNP analysis.
      Twenty-eight patients were documented as having experienced grade >/=2 late
      bladder or rectal toxicity (scoring system of Radiation Therapy Oncology Group)
      on at least one follow-up visit. We analyzed 49 SNPs in BRCA1, BRCA2, ESR1,
      XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF,
      NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, and CYP17A1 genes using
      the Pyrosequencing technique. RESULTS: Significant univariate associations with
      late rectal or bladder toxicity (grade >/=2) were found for XRCC3 (A>G 5'
      untranslated region NT 4541), LIG4 (T>C Asp(568)Asp), MLH1 (C>T, Val(219)Ile),
      CYP2D6*4 (G>A splicing defect), mean rectal and bladder dose, dose to 30% of
      rectum or bladder, and age <60 years. On Cox multivariate analysis, significant
      associations with toxicity were found for LIG4 (T>C, Asp(568)Asp), ERCC2 (G>A,
      Asp(711)Asp), CYP2D6*4 (G>A, splicing defect), mean bladder dose >60 Gy, and dose
      to 30% of rectal volume >75 Gy. CONCLUSIONS: In this study, we identified SNPs in
      LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk
      for complications arising from radiation therapy in prostate cancer.

PMID- 16638865
TI  - A phase 1 clinical study of intravenous administration of PV701, an oncolytic
      virus, using two-step desensitization.
AB  - PURPOSE: In a previous phase 1 study, adverse events, especially flu-like
      symptoms, were observed mainly following the first i.v. bolus dose of PV701, an
      oncolytic Newcastle disease virus. Desensitization to adverse events of
      subsequent doses occurred, allowing a 10-fold increase in the maximum tolerated
      dose for these doses. Although one-step desensitization (a single desensitizing
      dose with higher subsequent doses) addressed the tolerability of high repeat
      doses, additional testing was required to further improve tolerability of the
      initial dose. This study tested the hypothesis that two-step desensitization,
      using two dose increments before high repeat doses, would be well tolerated.
      EXPERIMENTAL DESIGN: Sixteen adults with incurable solid tumors were enrolled.
      Cycles consisted of six PV701 doses over 2 weeks followed by a 1-week rest. Doses
      1 to 2 were 1 and 12 x 10(9) plaque-forming units (pfu)/m(2), respectively,
      whereas doses 3 to 6 were escalated by cohort from 24 to 120 x 10(9) pfu/m(2).
      RESULTS: No dose-limiting toxicities were observed, permitting dose escalation
      through cohort 4 (1, 12, 120, 120, 120, 120 x 10(9) pfu/m(2)). Mild flu-like
      symptoms were common following the first infusion, diminished with repeated
      dosing, and were less pronounced than those seen previously. Tumor regression was
      observed in a patient with anal carcinoma who enrolled with stable disease
      following palliative radiotherapy. Four patients with clearly progressing cancer
      before enrollment had disease stabilization of >/=6 months. CONCLUSIONS: This
      novel two-step desensitization improved patient tolerability compared with the
      previous regimen. Toxicities were predictable and manageable. PV701, the first
      oncolytic virus to enter phase 1 i.v. testing, continues to show single-agent
      activity, warranting planned phase 2 trials.

PMID- 16638866
TI  - New intra-arterial drug delivery system for the treatment of liver cancer:
      preclinical assessment in a rabbit model of liver cancer.
AB  - BACKGROUND: In the fight against cancer, new drug delivery systems are attractive
      to improve drug targeting of tumors, maximize drug potency, and minimize systemic
      toxicity. We studied a new drug delivery system comprising microspheres, with
      unique properties allowing delivery of large amounts of drugs to tumors for a
      prolonged time, thereby decreasing plasma levels. Liver tumors, unlike
      nontumorous liver, draw most of their blood supply from the hepatic artery.
      Exploiting this property, we delivered drug-eluting microspheres/beads (DEB)
      loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx
      2). PURPOSE: The purpose of our study was to determine the pharmacokinetics and
      tumor-killing efficacy of DEB. RESULTS: Our results show that plasma
      concentration of doxorubicin was minimal in the animals treated with DEB at all
      time points (0.009-0.05 micromol/L), suggesting high tumor retention of
      doxorubicin. This was significantly lower (70-85% decrease in plasma
      concentration) than control animals treated with doxorubicin intra-arterially.
      Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g),
      remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76
      nmol/g), indicating continuous doxorubicin elution from beads. In control
      animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis
      (approaching 100%) was greatest at 7 days, with minimal adverse local side
      effects reflected in liver function tests results. The plasma concentration of
      doxorubicinol (doxorubicin main metabolite) was minimal. CONCLUSIONS: Our results
      support the concept of DEBs as an effective way to deliver drugs to tumor. This
      new technology may prove to be a useful weapon against liver cancer.

PMID- 16638867
TI  - Systemic antitumor effect of intratumoral injection of dendritic cells in
      combination with local photodynamic therapy.
AB  - PURPOSE: Photodynamic therapy (PDT), which is used clinically for the palliative
      treatment of cancer, induces local tumor cell death but has no effect on tumors
      in untreated sites. The purpose of this study was to determine if local PDT
      followed by intratumoral injection of naive dendritic cells (IT-DC) induces
      systemic antitumor immunity that can inhibit the growth of untreated as well as
      PDT + IT-DC-treated tumors. EXPERIMENTAL DESIGN: BALB/c or C57Bl/6 mice were
      injected s.c. with CT26 colorectal carcinoma cells and B16 melanoma cells,
      respectively, and following 10 to 12 days of tumor growth, the tumors were
      treated with PDT alone or PDT followed by IT-DC or IT-PBS. In other studies,
      tumors were established simultaneously in both lower flanks or in one flank and
      in the lungs, but only one flank was treated. RESULTS: Whereas neither PDT nor IT
      DC alone was effective, PDT + IT-DC eradicated both CT26 and B16 tumors in a
      significant proportion of animals and prolonged the survival of mice of which the
      tumors were not cured. The spleens of mice treated with PDT + IT-DC contained
      tumor-specific cytotoxic and IFN-gamma-secreting T cells whereas the spleens of
      control groups did not. Moreover, adoptive transfer of splenocytes from
      successfully treated CT26 tumor-free mice protected naive animals from a
      subsequent challenge with CT26, and this was mediated mainly by CD8 T cells. Most
      importantly, PDT plus IT-DC administered to one tumor site led to tumor
      regression at distant sites, including multiple lung metastases. CONCLUSIONS: PDT
      + IT-DC induces potent systemic antitumor immunity in mice and should be
      evaluated in the treatment of human cancer.

PMID- 16638868
TI  - Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a
      therapeutic T cell-mediated immune response that protects the host against
      syngeneic tumors of different histologic origin.
AB  - PURPOSE: We sought to demonstrate that a single systemic administration of
      L19mTNFalpha (a fusion protein constituted by the scFv L19 specific for the
      oncofetal ED-B domain of fibronectin and tumor necrosis factor alpha, TNFalpha)
      in combination with melphalan induced complete and long-lasting tumor eradication
      in tumor-bearing mice and triggered the generation of a specific T cell-based
      immune response that protects the animals from a second tumor challenge, as well
      as from challenges with syngeneic tumor cells of different histologic origin.
      EXPERIMENTAL DESIGN AND RESULTS: Treatment with L19mTNFalpha, in combination with
      melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164
      fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected
      challenges with the same tumor cells and, in a very high percentage of animals,
      also rejected challenges with syngeneic tumor cells of different histologic
      origin. In adoptive immunity transfer experiments, the splenocytes from tumor
      cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164
      fibrosarcoma. Similar results were also obtained in adoptive immunity transfer
      experiments using severely immunodepressed mice. Experiments using depleted
      splenocytes showed that T cells play a major role in tumor rejection.
      CONCLUSIONS: The results show that the selective targeting of mTNFalpha to the
      tumor enhances its immunostimulatory properties to the point of generating a
      therapeutic immune response against different histologically unrelated syngeneic
      tumors. These findings predicate treatment approaches for cancer patients based
      on the targeted delivery of TNFalpha to the tumor vasculature.

PMID- 16638869
TI  - A novel methionine aminopeptidase-2 inhibitor, PPI-2458, inhibits non-Hodgkin's
      lymphoma cell proliferation in vitro and in vivo.
AB  - PURPOSE: Fumagillin and related compounds have potent antiproliferative activity
      through inhibition of methionine aminopeptidase-2 (MetAP-2). It has recently been
      reported that MetAP-2 is highly expressed in germinal center B cells and germinal
      center-derived non-Hodgkin's lymphomas (NHL), suggesting an important role for
      MetAP-2 in proliferating B cells. Therefore, we determined the importance of
      MetAP-2 in normal and transformed germinal center B cells by evaluating the
      effects of MetAP-2 inhibition on the form and function of germinal centers and
      germinal center-derived NHL cells. EXPERIMENTAL DESIGN: To examine the activity
      of PPI-2458 on germinal center morphology, spleen sections from cynomolgus
      monkeys treated with oral PPI-2458 were analyzed. Antiproliferative activity of
      PPI-2458 was assessed on germinal center-derived NHL lines in culture. A MetAP-2
      pharmacodynamic assay was used to determine cellular MetAP-2 inhibition following
      PPI-2458 treatment. Finally, inhibition of MetAP-2 and proliferation by PPI-2458
      was examined in the human SR NHL line in culture and in implanted xenografts.
      RESULTS: Oral PPI-2458 caused a reduction in germinal center size and number in
      lymphoid tissues from treated animals. PPI-2458 potently inhibited growth (GI(50)
      = 0.2-1.9 nmol/L) of several NHL lines in a manner that correlated with MetAP-2
      inhibition. Moreover, orally administered PPI-2458 significantly inhibited SR
      tumor growth, which correlated with inhibition of tumor MetAP-2 (>85% at 100
      mg/kg) in mice. CONCLUSIONS: These results show the potent antiproliferative
      activity of PPI-2458 on NHL lines in vitro and oral antitumor activity in vivo
      and suggest the therapeutic potential of PPI-2458 as a novel agent for treatment
      of NHL should be evaluated in the clinical setting.

PMID- 16638870
TI  - Potent antitumor activity of an auristatin-conjugated, fully human monoclonal
      antibody to prostate-specific membrane antigen.
AB  - Prostate-specific membrane antigen (PSMA) is the prototypic cell-surface marker
      of prostate cancer and provides an attractive target for monoclonal antibody
      (mAb) targeted therapies. In this study, a novel antibody-drug conjugate (ADC)
      was generated by linking a fully human PSMA mAb to monomethylauristatin E (MMAE),
      a potent inhibitor of tubulin polymerization. The PSMA ADC was evaluated for
      antitumor activity in vitro and in a mouse xenograft model of androgen
      independent human prostate cancer. The PSMA ADC eliminated PSMA-expressing cells
      with picomolar potency and >700-fold selectivity in culture. When used to treat
      mice with established human C4-2 tumors, the PSMA ADC significantly improved
      median survival 9-fold relative to vehicle or isotype-matched ADC (P = 0.0018)
      without toxicity. Treatment effects were also manifest as significant (P =
      0.0068) reduction in serum levels of prostate-specific antigen (PSA).
      Importantly, 40% of treated animals had no detectable tumor or measurable PSA at
      day 500 and could be considered cured. The findings support development of PSMA
      antibody-auristatin conjugates for therapy of prostate cancer.

PMID- 16638871
TI  - Potential and toxicity of intravesical pemetrexed: a preclinical study in pigs.
AB  - PURPOSE: In search for a new drug for intravesical use in superficial urothelial
      cell carcinoma of the bladder, a pig model is used for pharmacokinetics and
      toxicity measurements after intravesically administered pemetrexed. EXPERIMENTAL
      DESIGN: In the dose escalation phase, two groups of two pigs received 5 and 10
      mg/kg pemetrexed intravesically; four groups of three pigs received 15, 20, 25,
      and 30 mg/kg, respectively. The well-being of the animals was monitored. Blood
      was studied for pharmacokinetic analysis and signs of myelosuppression.
      Posttreatment urine samples were collected to measure the concentration of
      pemetrexed after instillation. Twenty-four hours posttreatment, the animals were
      cystectomized and sacrificed. Histopathologic examination of the bladder wall was
      done. In the second study phase, five pigs were instilled weekly with the maximum
      tested dose for 6 weeks. The same methods were applied. RESULTS: All doses (5-30
      mg/kg) in the first study phase were well tolerated, enabling the use of 30 mg/kg
      in the second study phase. In both study phases, the pigs' well-being was not
      influenced. Full blood counts showed no sign of myelosuppression. Systemic
      absorption was not observed. Urine pemetrexed concentrations remained almost
      unchanged. Histopathologic examination of the bladder wall did not reveal
      significant abnormalities. Bladder mucosa remained intact at any time, without
      hemorrhage. CONCLUSIONS: Intravesically administered pemetrexed in pigs is well
      tolerated, not absorbed systemically, and causes no bladder wall toxicity.

PMID- 16638872
TI  - The bisphosphonate olpadronate inhibits skeletal prostate cancer progression in a
      green fluorescent protein nude mouse model.
AB  - PURPOSE: Metastatic bone disease is one of the major causes of morbidity and
      mortality in prostate cancer patients. Bisphosphonates are currently used to
      inhibit bone resorption and reduce tumor-induced skeletal complications. More
      effective bisphosphonates would enhance their clinical value. EXPERIMENTAL
      DESIGN: We tested several bisphosphonates in a green fluorescent protein (GFP)
      expressing human prostate cancer nude mouse model. The in vivo effects of four
      bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone
      tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer
      cells were visualized by whole-body fluorescence imaging and X-ray. RESULTS: The
      PC-3-GFP cells produced extensive bone lesions when injected into the tibia of
      immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was
      monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We
      showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid
      (olpadronate) was the most effective bisphosphonate treatment in reducing tumor
      burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray
      score significantly correlated. Reduced tumor growth in the bone was accompanied
      by reduced serum calcium, parathyroid hormone-related protein, and
      osteoprotegerin. CONCLUSIONS: The serum calcium, parathyroid hormone-related
      protein, and osteoprotegerin levels were significantly correlated with GFP area
      and X-ray scores. Treatment with olpadronate reduced tumor growth in the bone
      measured by GFP and X-ray imaging procedures. Imaging of GFP expression enables
      monitoring of tumor growth in the bone and the GFP results complement the X-ray
      assessment of bone disease. The data in this report suggest that olpadronate has
      potential as an effective inhibitor of the skeletal progression of clinical
      prostate cancer.

PMID- 16638873
TI  - Protective effect of erythropoietin and its carbamylated derivative in
      experimental Cisplatin peripheral neurotoxicity.
AB  - PURPOSE: Antineoplastic drugs, such as cisplatin (CDDP), are severely neurotoxic,
      causing disabling peripheral neuropathies with clinical signs known as
      chemotherapy-induced peripheral neurotoxicity. Cotreatment with neuroprotective
      agents and CDDP has been proposed for preventing or reversing the neuropathy.
      Erythropoietin given systemically has a wide range of neuroprotective actions in
      animal models of central and peripheral nervous system damage. However, the
      erythropoietic action is a potential cause of side effects if erythropoietin is
      used for neuroprotection. We have successfully identified derivatives of
      erythropoietin, including carbamylated erythropoietin, which do not raise the
      hematocrit but retain the neuroprotective action exerted by erythropoietin.
      EXPERIMENTAL DESIGN: We have developed previously an experimental chemotherapy
      induced peripheral neurotoxicity that closely resembles CDDP neurotoxicity in
      humans. The present study compared the effects of erythropoietin and carbamylated
      erythropoietin (50 microg/kg/d thrice weekly) on CDDP (2 mg/kg/d i.p. twice
      weekly for 4 weeks) neurotoxicity in vivo. RESULTS: CDDP given to Wistar rats
      significantly lowered their growth rate (P < 0.05), with slower sensory nerve
      conduction velocity (P < 0.001) and reduced intraepidermal nerve fibers density
      (P < 0.001 versus controls). Coadministration of CDDP and erythropoietin or
      carbamylated erythropoietin partially but significantly prevented the sensory
      nerve conduction velocity reduction. Both molecules preserved intraepidermal
      nerve fiber density, thus confirming their neuroprotective effect at the
      pathologic level. The protective effects were not associated with any difference
      in platinum concentration in dorsal root ganglia, sciatic nerve, or kidney
      specimens. CONCLUSIONS: These results widen the spectrum of possible use of
      erythropoietin and carbamylated erythropoietin as neuroprotectant drugs, strongly
      supporting their effectiveness.

PMID- 16638874
TI  - Rapamycin inhibits growth of premalignant and malignant mammary lesions in a
      mouse model of ductal carcinoma in situ.
AB  - PURPOSE: Rapamycin has been shown to have antitumor effects in various tumor
      models. To study the effect of rapamycin at different stages of breast cancer
      development, we used two unique mouse models of breast cancer with activated
      phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive
      and metastatic, and mammary intraepithelial neoplasia-outgrowths (MIN-O), a model
      for human ductal carcinoma in situ, are transplantable premalignant mammary
      lesions that develop invasive carcinoma with predictable latencies. Both of these
      models were derived from mammary lesions in Tg(MMTV-PyV-mT) mice. EXPERIMENTAL
      DESIGN: Met-1 tumors were used to study the effect of rapamycin treatment on
      invasive disease. Transplanted MIN-O model was used to study the effect of
      rapamycin on premalignant mammary lesions. Animals were in vivo micro-positron
      emission tomography imaged to follow the lesion growth and transformation to
      tumor during the treatment. Cell proliferation, angiogenesis, and apoptosis was
      assayed by immunohistochemistry. RESULTS: Rapamycin inhibited in vitro tumor cell
      proliferation and in vivo Met-1 tumor growth. The growth inhibition was
      correlated with dephosphorylation of mammalian target of rapamycin (mTOR)
      targets. Rapamycin treatment significantly reduced the growth of the premalignant
      MIN-O lesion, as well as tumor incidence and tumor burden. Growth inhibition was
      associated with reduced cell proliferation and angiogenesis and increased
      apoptosis. CONCLUSIONS: In PyV-mT mouse mammary models, rapamycin inhibits the
      growth of premalignant lesions and invasive tumors. Although the inhibitory
      effect of rapamycin was striking, rapamycin treatment did not completely
      obliterate the lesions.

PMID- 16638875
TI  - Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor
      mutants refractory to imatinib mesylate.
AB  - PURPOSE: The majority of gastrointestinal stromal tumors harbor mutations in the
      receptor tyrosine kinases KIT or platelet-derived growth factor receptor A
      (PDGFRA), and respond to treatment with the tyrosine kinase inhibitor imatinib.
      Some tumors, however, show primary resistance to imatinib treatment, and most
      others become resistant during treatment. The most common mechanism of imatinib
      resistance involves specific mutations in the kinase domains of KIT or PDGFRA. We
      tested the activity of SU11248, an orally active small-molecule tyrosine kinase
      inhibitor, to inhibit important imatinib-resistant KIT and PDGFRA mutants.
      EXPERIMENTAL DESIGN: Primary imatinib-resistant tumor cells and cell lines
      expressing clinically identified imatinib-resistant KIT-V654A, KIT-T670I, or
      PDGFRA-D842V mutant isoforms were evaluated for sensitivity to SU11248 by Western
      immunoblotting and proliferation assays. Three patients with the KIT-V654A
      mutation were treated with SU11248. RESULTS: Based on ex vivo assays, SU11248
      potently inhibits KIT kinase activity of V654A and T670I mutants and suppresses
      proliferation of the cells expressing these mutations. Sensitivity of KIT-V654A
      and KIT-T670I mutants to SU11248 was confirmed using cell lines expressing these
      mutants. In contrast, SU11248 did not potently inhibit the PDGFRA-D842V mutant.
      In agreement with these results, two of the three imatinib-resistant patients
      with the KIT-V654A mutation responded to SU11248 treatment. CONCLUSIONS: These
      studies suggest that SU11248 may be a useful therapeutic agent to treat
      gastrointestinal stromal tumors harboring the imatinib-resistant KIT-V654A or KIT
      T670I mutations, but it has no effect on the activity of the PDGFRA-D842V mutant.
      Specific kinase inhibitors should be designed to inhibit the constitutive
      activating PDGFRA mutation at codon 842.

PMID- 16638876
TI  - Roles of nitric oxide synthase inhibition and vascular endothelial growth factor
      receptor-2 inhibition on vascular morphology and function in an in vivo model of
      pancreatic cancer.
AB  - PURPOSE: Both nitric oxide (NO) and vascular endothelial growth factor (VEGF)
      mediate tumor vascular function. Because these molecules regulate one another's
      expression, we hypothesized that NO synthase (NOS) inhibition produces effects
      comparable to those of anti-VEGF therapy on human pancreatic cancer xenografts.
      EXPERIMENTAL DESIGN: L3.6pl human pancreatic cancer cells were s.c. implanted in
      nude mice. On day 6, mice were randomized to receive (a) PBS (control), (b) DC101
      [VEGF receptor 2 (VEGFR-2) antibody] by i.p. injection, (c) N-nitro-l-arginine
      (NNLA; NOS inhibitor) in the drinking water, or (d) both DC101 and NNLA. Mice
      were killed on day 20. RESULTS: DC101 and NNLA as single agents inhibited tumor
      growth by approximately 50% to 60% (P < 0.008 for both). Furthermore, combined
      therapy inhibited mean tumor growth by 89% (P < 0.008). Combined inhibition of
      VEGFR-2 and NOS also decreased mean vessel counts by 65% (P < 0.03) and vessel
      area by 80% versus controls (P < 0.001). In contrast to DC101 where vessel
      diameter was similar to control, NNLA decreased mean vessel diameter by 42% (P <
      0.001). NNLA also led to a 54% (P < 0.03) decrease in tumor uptake of the
      perfusion marker Hoechst 33342 versus controls whereas DC101 decreased Hoechst
      33342 staining by 43% (P < 0.03). The combination of inhibitors decreased
      perfusion by 73% (P < 0.03). CONCLUSIONS: Although VEGFR-2 can mediate NOS
      activity, the combination of VEGFR-2 and NOS inhibition significantly increased
      the antivascular effect over single agent therapy. The addition of NOS inhibition
      led to an even further alteration of tumor vessel morphology and vascular
      perfusion compared with VEGFR-2 blockade, suggesting that NO and VEGFR-2 have
      distinct but complementary effects on the tumor vasculature.

PMID- 16638877
TI  - Evaluation of antitumoral properties of the protease inhibitor indinavir in a
      murine model of hepatocarcinoma.
AB  - PURPOSE: Accumulating evidences show a higher incidence of hepatic neoplasm in
      HIV/hepatitis C virus (HCV)-coinfected individuals compared with HCV-monoinfected
      patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted
      angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to
      evaluate the antineoplastic potential activities of the protease inhibitor
      indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. EXPERIMENTAL
      DESIGN: We analyzed effects of indinavir on cell growth and invasiveness in Huh7
      and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same
      cells in nude mice. Morphologic and molecular analyses on explanted tumors were
      carried out to evaluate vascularization and apoptosis. RESULTS: We observed a
      reduced ability to invade an in vitro extracellular matrix for both cell lines
      treated with indinavir compared with controls (P = 0,001). Moreover, indinavir
      treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation,
      whereas there was no effect on cell proliferation. The drug was also able to
      delay in vivo tumor growth. The inhibition of tumor growth was statistically
      significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover,
      the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel
      count and apoptotic index by terminal deoxynucleotide transferase-mediated nick
      end labeling in explanted tumors. Finally, treatment with indinavir did not block
      the production of vascular endothelial growth factor in the tumors. CONCLUSION:
      Indinavir could be helpful to prevent the development of hepatocarcinomas in
      HIV/HCV-coinfected individuals. In view of the current trend to substitute
      protease inhibitors with other antiretroviral agents, this information may have
      clinical implications.

PMID- 16638878
TI  - Preclinical differentiation between apparently safe and potentially hepatotoxic
      applications of TRAIL either alone or in combination with chemotherapeutic drugs.
AB  - PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L)
      exhibits potent antitumor activity on systemic administration in nonhuman
      primates without deleterious side effects for normal tissue. However, there is a
      controversy about the potential toxicity of TRAIL on human hepatocytes. The use
      of different recombinant TRAIL forms only partially explains the contradicting
      reports on TRAIL sensitivity in primary human hepatocytes (PHH). EXPERIMENTAL
      DESIGN: To clarify this issue, we comprehensively tested four different
      recombinant forms of TRAIL for their apoptosis-inducing capacity on PHH obtained
      from a total of 55 human livers between day 1 and day 8 of in vitro culture.
      RESULTS: One day after single-cell isolation, all but one recombinant form of
      TRAIL [i.e., an untagged form of TRAIL (TRAIL.0)] induced apoptosis in PHH.
      Apoptosis induction by TRAIL in these cells could only be fully inhibited by
      concomitant blockade of TRAIL receptor 1 and TRAIL receptor 2. At day 4 of in
      vitro culture, when surrogate markers indicated optimal hepatocyte in vitro
      function, only high doses of cross-linked FLAG-TRAIL killed PHH whereas the other
      three recombinant TRAIL forms did not. Strikingly, cotreatment of day 4 PHH with
      cisplatin sensitized for TRAIL-induced apoptosis whereas 5-fluorouracil,
      etoposide, gemcitabine, irinotecan, or oxaliplatin, which are commonly used in
      the treatment of gastrointestinal cancers, did not. CONCLUSION: Our data show
      that whereas TRAIL alone or together with selected chemotherapeutic drugs seems
      to be safe, the combination of TRAIL with cisplatin is toxic to PHH.

PMID- 16638881
TI  - Impact of blood sampling on circulating tissue inhibitors of metalloproteinases.

PMID- 16638883
TI  - Comments on plasmalemmal vesicle associated protein-1 as a novel marker
      implicated in brain tumor angiogenesis.

PMID- 16638884
TI  - APA, NAMI, NMHA, and evidence-based behavioural medicine: a comment.

PMID- 16638885
TI  - Review: longer duration of untreated psychosis is associated with worse outcome
      in people with first episode psychosis.

PMID- 16638886
TI  - Cognitive function is not a prognostic factor for long term functional status in
      older people.

PMID- 16638887
TI  - The short form adult attention deficit/hyperactivity self-report scale is a
      useful diagnostic measure.

PMID- 16638888
TI  - Adding a question that asks whether help is wanted improves sensitivity of a
      depression screening tool.

PMID- 16638889
TI  - Risperidone effectively increases rates of symptomatic remission of acute mania
      in people with bipolar disorder.

PMID- 16638891
TI  - Olanzapine plus fluoxetine reduce depressive symptoms faster than either drug
      alone in people with treatment resistant depression.

PMID- 16638890
TI  - Aripiprazole reduces acute mania compared with haloperidol in bipolar I disorder
      and causes fewer adverse effects.

PMID- 16638892
TI  - Review: cognitive behavioural therapy is more effective than control and
      similarly effective to pharmacotherapy for generalised anxiety disorder.

PMID- 16638893
TI  - Review: psychological treatments improve pathological gambling in the short and
      long term.

PMID- 16638894
TI  - Methylphenidate hydrochloride reduces hyperactivity in children with pervasive
      development disorders.

PMID- 16638895
TI  - Integrated care improves one year outcomes in first episode psychosis.

PMID- 16638896
TI  - First episode psychosis: olanzapine and haloperidol provide similar improvements
      in quality of life and social functioning.

PMID- 16638897
TI  - Adding sarcosine, but not D-serine, to risperidone improves symptoms in people
      with acute phase schizophrenia.

PMID- 16638898
TI  - Telephone delivered cognitive behavioural therapy improves depression in people
      with multiple sclerosis faster than telephone delivered supportive emotion
      focused therapy.

PMID- 16638899
TI  - Counselling and cognitive behavioural therapy reduce anxiety and depression in
      women with postnatal depression.

PMID- 16638900
TI  - A universally administered primary prevention programme for depression reduces
      symptoms in German adolescents with low self-efficacy.

PMID- 16638901
TI  - Continued escitalopram reduces risk of relapse in people with generalised social
      anxiety disorder.

PMID- 16638902
TI  - Combination treatment of behaviour therapy and medication significantly reduces
      obsessive-compulsive symptoms in people who have responded to pharmacotherapy.

PMID- 16638903
TI  - Review: atypical antipsychotic drugs slightly increase mortality rates in elderly
      people with dementia.

PMID- 16638904
TI  - Abstinence incentives improve stimulant abusers' compliance with community-based
      psychosocial treatments.

PMID- 16638905
TI  - Discontinuing risperidone results in relapse in children with autism spectrum
      disorders.

PMID- 16638906
TI  - Adolescent panic attacks are associated with increased risk of personality
      disorder as a young adult.

PMID- 16638907
TI  - Anxiety disorders are a risk factor for suicidal behaviour.

PMID- 16638908
TI  - Major depressive disorder is common in the US among Native Americans, women, the
      middle aged, the poor, and widowed, separated, or divorced people.

PMID- 16638909
TI  - Molecular control of cell cycle progression in the pancreatic beta-cell.
AB  - Type 1 and type 2 diabetes both result from inadequate production of insulin by
      the beta-cells of the pancreatic islet. Accordingly, strategies that lead to
      increased pancreatic beta-cell mass, as well as retained or enhanced function of
      islets, would be desirable for the treatment of diabetes. Although pancreatic
      beta-cells have long been viewed as terminally differentiated and irreversibly
      arrested, evidence now indicates that beta-cells can and do replicate, that this
      replication can be enhanced by a variety of maneuvers, and that beta-cell
      replication plays a quantitatively significant role in maintaining pancreatic
      beta-cell mass and function. Because beta-cells have been viewed as being unable
      to proliferate, the science of beta-cell replication is undeveloped. In the past
      several years, however, this has begun to change at a rapid pace, and many
      laboratories are now focused on elucidating the molecular details of the control
      of cell cycle in the beta-cell. In this review, we review the molecular details
      of cell cycle control as they relate to the pancreatic beta-cell. Our hope is
      that this review can serve as a common basis and also a roadmap for those
      interested in developing novel strategies for enhancing beta-cell replication and
      improving insulin production in animal models as well as in human pancreatic beta
      cells.

PMID- 16638910
TI  - Mechanism underlying flow stimulation of sodium absorption in the mammalian
      collecting duct.
AB  - Vectorial Na(+) absorption across the aldosterone-sensitive distal nephron plays
      a key role in the regulation of extracellular fluid volume and blood pressure.
      Within this nephron segment, Na(+) diffuses from the urinary fluid into principal
      cells through an apical, amiloride-sensitive, epithelial Na(+) channel (ENaC),
      which is considered to be the rate-limiting step for Na(+) absorption. We have
      reported that increases in tubular flow rate in microperfused rabbit cortical
      collecting ducts (CCDs) lead to increases in net Na(+) absorption and that
      increases in laminar shear stress activate ENaC expressed in oocytes by
      increasing channel open probability. We therefore examined whether flow
      stimulates net Na(+) absorption (J(Na)) in CCDs by increasing channel open
      probability or by increasing the number of channels at the apical membrane. Both
      baseline and flow-stimulated J(Na) in CCDs were mediated by ENaC, as J(Na) was
      inhibited by benzamil. Flow-dependent increases in J(Na) were observed following
      treatment of tubules with reagents that altered membrane trafficking by
      disrupting microtubules (colchicine) or Golgi (brefeldin A). Furthermore,
      reducing luminal Ca(2+) concentration ([Ca(2+)]) or chelating intracellular
      [Ca(2+)] with BAPTA did not prevent the flow-dependent increase in J(Na).
      Extracellular trypsin has been shown to activate ENaC by increasing channel open
      probability, and we observed that trypsin significantly enhanced J(Na) when
      tubules were perfused at a slow flow rate. However, trypsin did not further
      enhance J(Na) in CCDs perfused at fast flow rates. Similarly, the shear-induced
      increase in benzamil-sensitive J(Na) in oocytes expressing protease resistance
      ENaC mutants was similar to that of controls. Our results suggest the rise in
      J(Na) accompanying increases in luminal flow rates reflects an increase in
      channel open probability.

PMID- 16638911
TI  - Glucocorticoid impairs growth of kidney outer medulla and accelerates loop of
      Henle differentiation and urinary concentrating capacity in rat kidney
      development.
AB  - In the rat, urinary concentrating ability develops progressively during the third
      postnatal (P) week and nearly reaches adult level at weaning (P21) governed by a
      rise in circulating glucocorticoid. Elevated extracellular osmolality can lead to
      growth arrest of epithelial cells. We tested the hypothesis that supranormal
      exposure of rat pups to glucocorticoid before the endogenous surge enhances
      urinary concentrating ability but inhibits renomedullary cell proliferation.
      Proliferating-cell nuclear antigen (PCNA)-positive cells shifted from the
      nephrogenic zone in the first postnatal week to Tamm-Horsfall-positive thick
      ascending limb (TAL) cells at the corticomedullary junction at P10-14. Renal PCNA
      protein abundance was stable in the suckling period and decreased 10-fold after
      weaning. Renal PCNA protein abundance decreased in response to dexamethasone
      (DEXA; 100 microg x kg(-1) x day(-1), P8-12). Prolonged administration of DEXA
      (P1-P11) reduced selectively the area and thickness of the outer medulla and the
      number of PCNA-positive cells. DEXA (P8-12) increased urinary and papillary
      osmolality in normohydrated and water-deprived pups and led to osmotic
      equilibrium between interstitium and urine, whereas apoptotic and GADD153
      positive cells increased in the inner medulla. TAL-associated NaCl transporters
      Na-K-2Cl cotransporter, Na-K-ATPase-alpha(1), Na/H exchanger type 3, and ROMK
      increased significantly at weaning and in response to DEXA. We conclude that a
      low level of circulating glucocorticoid is permissive for proliferation of
      Henle's loop and the outer medulla before weaning. A reduced papillary tonicity
      is a crucial factor for the reduced capacity to concentrate urine during
      postnatal kidney development. We speculate that supranormal exposure to
      glucocorticoid in the suckling period can alter kidney medullary structure and
      function permanently.

PMID- 16638912
TI  - Acute renal failure: determinants and characteristics of the injury-induced
      hyperinflammatory response.
AB  - Acute renal failure (ARF) markedly sensitizes mice to endotoxin (LPS), as
      evidenced by exaggerated renal cytokine/chemokine production. This study sought
      to further characterize this state by testing the following: 1) does anti
      inflammatory heme oxygenase-1 (HO-1) upregulation in selected ARF models prevent
      this response? 2) Is the ARF hyperresponsive state specifically triggered by LPS?
      3) Does excess iNOS activity/protein nitrosylation participate in this
      phenomenon? and 4) are upregulated Toll receptors involved? Mice with either 1)
      rhabdomyolysis-induced ARF (massive HO-1 overexpression), 2) cisplatin
      nephrotoxicity, 3) or HO-1 inhibition (Sn protoporphyrin) were challenged with
      either LPS (a TLR4 ligand), lipoteichoic acid (LTA; a TLR2 ligand), or vehicle.
      Two hours later, renal and plasma TNF-alpha/mRNA, MCP-1/mRNA, renal
      nitrotyrosine/iNOS mRNA, and plasma cytokines were assessed. Renal TLR4 was
      gauged by mRNA and Western blot analysis. Both ARF models markedly hyperresponded
      to both LPS and LTA, culminating in exaggerated TNF-alpha, MCP-1, and
      iNOS/nitrotryosine increments. This was despite the fact that HO-1 exerted anti
      inflammatory effects. TLR4 levels were either normal (cisplatin), or markedly
      depressed ( approximately 50%; rhabdomyolysis) in the ARF kidneys, despite the
      LPS hyperresponsive state. 1) The ARF kidney can hyperrespond to chemically
      dissimilar Toll ligands; 2) HO-1 does not prevent this response; 3) excess
      NO/protein nitrosylation can result; and 4) this hyperresponsiveness can be
      expressed with either normal or reduced renal TLR4 expression. This suggests that
      diverse signaling pathways may be involved.

PMID- 16638913
TI  - Prostasin attenuates inducible nitric oxide synthase expression in
      lipopolysaccharide-induced urinary bladder inflammation.
AB  - Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with
      epithelial sodium channel activation and tumor invasion suppression activities.
      We identified the bladder as an expression site of prostasin. In the mouse,
      prostasin mRNA expression was detected by reverse transcription and real-time
      polymerase chain reaction in the bladder, and the prostasin protein was localized
      by immunohistochemistry in the urothelial cells. In mice injected
      intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA
      expression was downregulated, whereas the expression of inducible nitric oxide
      synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-gamma (IFN-gamma), TNF
      alpha, IL-1beta, and IL-6 was upregulated. Viral promoter-driven expression of
      the human prostasin homolog in the bladder of transgenic mice attenuated the LPS
      induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF
      alpha, IL-1beta, and IL-6 expression, however, was not reduced by prostasin
      transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid
      into mouse bladder produced similar attenuation effects on LPS-induced iNOS
      expression, while not affecting COX-2 or cytokine induction. Mice receiving
      plasmid expressing a catalytic mutant prostasin did not manifest the iNOS
      induction attenuation phenotype. We propose a proteolytic mechanism for prostasin
      to intercept cytokine signaling during LPS-induced bladder inflammation.

PMID- 16638914
TI  - Propofol-induced priapism, a case confirmed with rechallenge.
AB  - OBJECTIVE: To report a case of propofol-induced priapism. CASE SUMMARY: A 17-year
      old male receiving propofol for induction of anesthesia during a cardiac ablation
      procedure developed priapism that required medical intervention and
      discontinuation of propofol. The priapism developed after a total propofol dose
      of 550 mg, lasted for 2 hours, and resolved immediately following medical
      intervention. The following day, the patient underwent a transesophageal
      echocardiogram and received a total propofol dose of 40 mg throughout the
      procedure. He again developed priapism, which resolved within one hour without
      medical intervention. DISCUSSION: Priapism experienced by this patient is
      considered to be drug-induced because of the temporal relationship, recurrence
      with rechallenge, and dose-response relationship. Using the Naranjo probability
      scale, we determined that propofol was a highly probable causative agent of
      priapism in this patient. CONCLUSIONS: Although, as of April 4, 2006, this
      adverse effect has not been previously reported, there is a strong correlation of
      propofol to priapism in this patient. Clinicians should be aware of this adverse
      effect.

PMID- 16638915
TI  - Update on rimonabant--a selective cannabinoid CB1 antagonist.

PMID- 16638916
TI  - Type of preexisting lipid therapy predicts LDL-C response to ezetimibe.
AB  - BACKGROUND: Ezetimibe as monotherapy or in combination with statins effectively
      lowers low-density lipoprotein cholesterol (LDL-C). However, there are few
      reports of ezetimibe's effect when added to ongoing non-statin lipid-lowering
      drugs or combination lipid-lowering therapy. OBJECTIVE: To evaluate the impact of
      preexisting lipid therapy on LDL-C response to ezetimibe. METHODS: We performed a
      retrospective review of all patients started on ezetimibe therapy at the Veterans
      Affairs Long Beach Healthcare System between March 1, 2003, and March 1, 2005. We
      calculated the ezetimibe-induced percent change in LDL-C in patients without
      concomitant changes in other lipid-lowering medications. We then stratified the
      population according to the type and number of preexisting lipid therapies and
      compared the LDL-C-lowering efficacy of ezetimibe among these groups. RESULTS:
      Overall, ezetimibe was associated with a 23.0% reduction in LDL-C. Patients with
      preexisting statin monotherapy had significantly greater LDL-C reduction with
      ezetimibe than did those with preexisting non-statin drugs (-26.1% vs -9.3%; p =
      0.0138). In patients with no preexisting lipid therapy (n = 58), monotherapy (n =
      115), double therapy (n = 36), or triple therapy (n = 9), ezetimibe decreased LDL
      C by 17.3%, 21.4%, 33.5%, and 38.1%, respectively. This stepwise trend in
      increased ezetimibe efficacy was statistically significant, even with adjustments
      for baseline LDL-C. CONCLUSIONS: Ezetimibe's LDL-C-lowering effects are most
      pronounced when added to preexisting combination lipid therapy. It appears to be
      more effective when added to statin therapy compared with other lipid-lowering
      therapies.

PMID- 16638917
TI  - Fluconazole-resistant pseudomembranous oral candidiasis.

PMID- 16638918
TI  - Quality of medication records and use of pharmacy resources in community
      residential care facilities.
AB  - BACKGROUND: In community residential care (CRC) facilities, medication
      administration is often performed by unlicensed personnel with minimal knowledge
      in medication use. Medication management is one of the top 3 quality-of-care
      issues facing these facilities. OBJECTIVE: To examine the type of medication
      assistance residents received, determine the proportion of facilities that used
      pharmacy resources, and examine the quality of facility medication records in CRC
      facilities (eg, adult family homes, adult residential care, assisted living
      facilities). METHODS: Baseline in-person interviews were conducted with 349
      residents and 299 facility providers in the Puget Sound region of Washington.
      Information was also obtained from facility medication records at enrollment and
      state databases. A pharmacist determined quality of the records using a
      standardized form. RESULTS: The average resident was a 78-year-old white female
      taking 7 drugs. Medication records that were computer generated were
      significantly less likely to have misspelled names of drugs and errors in or
      absence of dose, directions for use, and route of administration. Overall, 26.3%
      of facilities reported that a consultant pharmacist reviewed residents'
      medication lists, 52.0% reported the use of preprinted lists, and 75.6% received
      prepackaged medications from the pharmacy. Adult family homes, the smallest
      facility type, were the least likely to use pharmacy-related services.
      CONCLUSIONS: The quality of handwritten medication records was a concern in CRC
      facilities. These facilities may benefit from services offered by pharmacies that
      may enhance medication management, many of which were underutilized.

PMID- 16638919
TI  - Women in pharmacy 2006: a good match.

PMID- 16638920
TI  - Patient Safety and Quality Improvement Act of 2005.
AB  - OBJECTIVE: To review Public Law (PL) 109-41-the Patient Safety and Quality
      Improvement Act of 2005 (PSQIA)-and summarize key medication error research that
      contributed to congressional recognition of the need for this legislation. DATA
      SOURCES: Relevant publications related to medication error research, patient
      safety programs, and the legislative history of and commentary on PL 109-41,
      published in English, were identified by MEDLINE, PREMEDLINE, Thomas (Library of
      Congress), and Internet search engine-assisted searches using the terms
      healthcare quality, medication error, patient safety, PL 109-41, and quality
      improvement. Additional citations were identified from references cited in
      related publications. STUDY SELECTION AND DATA EXTRACTION: All relevant
      publications were reviewed. Summarization of the PSQIA was carried out by legal
      textual analysis. DATA SYNTHESIS: PL 109-41 provides privilege and
      confidentiality for patient safety work product (PSWP) developed for reporting to
      patient safety organizations (PSOs). It does not establish federal mandatory
      reporting of significant errors; rather, it relies on existing state reporting
      systems. The Act does not preempt stronger state protections for PSWP. The Agency
      for Healthcare Research and Quality is directed to certify PSOs and promote the
      establishment of a national network of patient safety databases. Whistleblower
      protection and penalties for unauthorized disclosure of PSWP are among its
      enforcement mechanisms. CONCLUSIONS: The Act protects clinicians who report minor
      errors to PSOs and protects the information from disclosure, but providers must
      increasingly embrace a culture of interdisciplinary concern for patient safety if
      this protection is to have real impact on patient care.

PMID- 16638921
TI  - Nonsteroidal antiinflammatory drugs during third trimester and the risk of
      premature closure of the ductus arteriosus: a meta-analysis.
AB  - BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) are increasingly being
      used during pregnancy to treat a variety of conditions. An evaluation of the risk
      of premature closure of the ductus arteriosus is useful in determining the safety
      of NSAIDs at different stages of pregnancy. OBJECTIVE: To determine whether NSAID
      use during the third trimester of pregnancy is associated with an increased risk
      of premature constriction of the ductus arteriosus. METHODS: A systematic review
      was conducted of MEDLINE (1966-2004), Embase (1980-2004), and the Cochrane
      Database of Systematic Reviews (1991-2004). Summary estimates of the odds ratios,
      comparing ductal outcomes in exposed and unexposed fetuses, and their 95%
      confidence intervals were calculated assuming a random effects model. RESULTS:
      Based on 217 patients exposed to indomethacin and 221 to placebo, the risk of
      ductal closure was 15-fold higher in the group of women exposed to NSAIDs
      compared with those receiving either placebo or other NSAIDs (8 studies; OR =
      15.04, 95% CI 3.29 to 68.68). There was no significant increased risk of ductal
      closure in the infants of women treated with indomethacin compared with those
      receiving other drugs (4 studies; OR = 2.12, 95% CI 0.48 to 9.25). Similar
      results were found when calculating rate differences. CONCLUSIONS: Short-term use
      of NSAIDs in late pregnancy is associated with a significant increase in the risk
      of premature ductal closure.

PMID- 16638922
TI  - Occurrence and impact of unanticipated variation in intravenous methotrexate
      dosing.
AB  - BACKGROUND: Studies using direct measurement suggest that the doses of up to 65%
      of drug infusions are outside industry standards. These preparation-associated
      errors occur despite routine safety procedures. As of April 5, 2006, the clinical
      impact of these errors had not been evaluated. OBJECTIVE: To measure the
      occurrence and associated clinical outcomes of variations in intravenous
      methotrexate dosing. METHODS: A prospective observational study was performed on
      47 methotrexate infusions of 800 mg/m2 that were administered to 19 children with
      acute lymphoblastic leukemia. Serum methotrexate concentrations were measured at
      the end of the infusions, which were administered over 24 hours. The total
      methotrexate dose was determined by direct measurement of the concentration and
      the volume of each infusion. RESULTS: Dosing errors greater than or equal to 10%
      occurred in 11 (23%) infusions and ranged from -61% to 55% of the ideal dose.
      Repeated measures regression analysis found the measured total methotrexate dose
      was not significantly associated with the serum methotrexate concentration (p =
      0.58) or with clinical toxicities. The methotrexate dose administered over the
      last hours of infusion (p = 0.006) and the serum creatinine level at diagnosis (p
      = 0.05) were the most significant predictors of the methotrexate concentration.
      High methotrexate concentrations were significantly associated with increased
      hepatic aminotransferase levels; however, the degree of elevation was of limited
      clinical relevance. CONCLUSIONS: While unexpected errors in drug dosing are more
      common than is suggested by other methods, the clinical impact observed in this
      model of methotrexate infusion was not demonstrably greater than medication
      errors described by other methods. Subsequent studies in this model of dosing
      error will require larger sample sizes, and other drugs should be evaluated.

PMID- 16638923
TI  - Ethanol-induced increase in the metabolic clearance of 1,1,1-trichloroethane in
      human volunteers.
AB  - This study evaluated the effect of moderate doses of ethanol over a short period
      of time on the toxicokinetics of an organic solvent, 1,1,1-trichloroethane. A
      group of 10 moderate drinkers were recruited and exposed via inhalation for 2 h
      to a low concentration of 1,1,1-trichloroethane (175 ppm) on two separate
      occasions. Subjects were administered ethanol (0.35 g/kg body weight) on each of
      the 7 days preceding one of the exposures. Blood and urine samples were collected
      during and following each exposure, with blood analyzed for 1,1,1-trichloroethane
      and urine analyzed for the metabolites of 1,1,1-trichloroethane: trichloroethanol
      and trichloroacetic acid. Prior ethanol consumption resulted in a significant
      increase in apparent metabolic clearance of 1,1,1-trichloroethane (mean increase
      = 25.4%). The results of this study demonstrate that ethanol consumption over
      time can affect the rate at which an organic solvent is cleared through
      metabolism in humans. For chemicals with toxic metabolic products, this inductive
      effect of ethanol consumption on the rate of biotransformation could be
      potentially harmful to exposed individuals. Metabolic clearance of compounds with
      high hepatic extraction may not be affected by enzyme induction as it is likely
      that these compounds are essentially completely metabolized while passing through
      the liver.

PMID- 16638924
TI  - Correlation of brain magnetic resonance imaging changes with pallidal manganese
      concentrations in rhesus monkeys following subchronic manganese inhalation.
AB  - High-dose manganese exposure is associated with parkinsonism. Because manganese
      is paramagnetic, its relative distribution within the brain can be examined using
      magnetic resonance imaging (MRI). Herein, we present the first comprehensive
      study to use MRI, pallidal index (PI), and T(1) relaxation rate (R1) in concert
      with chemical analysis to establish a direct association between MRI changes and
      pallidal manganese concentration in rhesus monkeys following subchronic
      inhalation of manganese sulfate (MnSO(4)). Monkeys exposed to MnSO(4) at > or =
      0.06 mg Mn/m(3) developed increased manganese concentrations in the globus
      pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum.
      Manganese concentrations within the olfactory system of the MnSO(4)-exposed
      monkeys demonstrated a decreasing rostral-caudal concentration gradient, a
      finding consistent with olfactory transport of inhaled manganese. Marked MRI
      signal hyperintensities were seen within the olfactory bulb and the globus
      pallidus; however, comparable changes could not be discerned in the intervening
      tissue. The R1 and PI were correlated with the pallidal manganese concentration.
      However, increases in white matter manganese concentrations in MnSO(4)-exposed
      monkeys confounded the PI measurement and may lead to underestimation of pallidal
      manganese accumulation. Our results indicate that the R1 can be used to estimate
      regional brain manganese concentrations and may be a reliable biomarker of
      occupational manganese exposure. To our knowledge, this study is the first to
      provide evidence of direct olfactory transport of an inhaled metal in a nonhuman
      primate. Pallidal delivery of manganese, however, likely arises primarily from
      systemic delivery and not directly from olfactory transport.

PMID- 16638925
TI  - Investigation of drug-induced mitochondrial toxicity using fluorescence-based
      oxygen-sensitive probes.
AB  - Mitochondrial dysfunction is a common mechanism of drug-induced toxicity. Early
      identification of new chemical entities (NCEs) that perturb mitochondrial
      function is of significant importance to avoid attrition in later stages of drug
      development. One of the most informative ways of assessing mitochondrial
      dysfunction is by measuring mitochondrial oxygen consumption. However, the
      conventional polarographic method of measuring oxygen consumption is not amenable
      to high sample throughput or automation. We present an alternative, low-bulk,
      high-throughput approach to the analysis of isolated-mitochondrial oxygen
      consumption using luminescent oxygen-sensitive probes. These probes are
      dispensable and are analyzed in standard microtitre plates on a fluorescence
      plate reader. Respiratory substrate and adenosine diphosphate (ADP) dependencies
      of mitochondrial oxygen consumption were assessed using the fluorescence-based
      method, and results compared favourably to conventional polarographic analysis.
      To assess assay performance, the method was then applied to the analysis of a
      panel of classical modulators of oxidative phosphorylation. The effect of
      uncoupler concentration was analyzed in detail to identify factors which would be
      important in applying this method to large scale NCE screening and mechanistic
      investigations. Results demonstrate that the 96-well format can accommodate up to
      approximately 200 compounds/day at a single concentration or alternatively IC(50)
      values can be generated for approximately 25 compounds. Throughput may be
      increased by moving to a 384-well plate format.

PMID- 16638927
TI  - Ocular adnexal lymphoma: a review of clinicopathologic features and treatment
      options.
AB  - The recent literature shows that interest in ocular adnexal lymphomas and their
      biologic and clinical characteristics--along with their possible association with
      Chlamydia psittaci infection and therapeutic management with rituximab or anti
      Chlamydia psittaci antibiotic therapy--is considerable. These new data have
      modified the previously reported features of this disease and have made an
      updated review of the literature necessary. The aims of this review are to
      present the current knowledge on the biology of these lymphomas, their clinical
      features and prognostic factors, and the panel of all available treatment
      options.

PMID- 16638928
TI  - Correction of sickle cell disease by homologous recombination in embryonic stem
      cells.
AB  - Previous studies have demonstrated that sickle cell disease (SCD) can be
      corrected in mouse models by transduction of hematopoietic stem cells with
      lentiviral vectors containing antisickling globin genes followed by
      transplantation of these cells into syngeneic recipients. Although self
      inactivating (SIN) lentiviral vectors with or without insulator elements should
      provide a safe and effective treatment in humans, some concerns about insertional
      mutagenesis persist. An ideal correction would involve replacement of the sickle
      globin gene (beta(S)) with a normal copy of the gene (beta(A)). We recently
      derived embryonic stem (ES) cells from a novel knock-in mouse model of SCD and
      tested a protocol for correcting the sickle mutation by homologous recombination.
      In this paper, we demonstrate the replacement of the human beta(S)-globin gene
      with a human beta(A)-globin gene and the derivation of mice from these cells. The
      animals produce high levels of normal human hemoglobin (HbA) and the pathology
      associated with SCD is corrected. Hematologic values are restored to normal
      levels and organ pathology is ameliorated. These experiments provide a foundation
      for similar studies in human ES cells derived from sickle cell patients. Although
      efficient methods for production of human ES cells by somatic nuclear transfer
      must be developed, the data in this paper demonstrate that sickle cell disease
      can be corrected without the risk of insertional mutagenesis.

PMID- 16638929
TI  - Simultaneous bone marrow and intestine transplantation promotes marrow-derived
      hematopoietic stem cell engraftment and chimerism.
AB  - Organ allografts have been shown to provide a syngeneic microenvironment for
      organ-based donor hematopoietic stem cells to maintain long-lasting chimerism
      after transplantation. We hypothesized that organ allografts would also support
      engraftment and hematopoiesis of adjunctively infused donor marrow stem cells,
      syngeneic to organ grafts, in nonmyeloablated recipients. In BN-to-LEW and GFP-to
      ACI rat combinations, donor bone marrow (BM) infusion together with small
      intestine transplantation (SITx) under short-course tacrolimus immunosuppression
      resulted in persistent macrochimerism (more than 5%) for 150 days. In contrast,
      after BM infusion or SITx alone, chimerism was temporary and disappeared by day
      100. Y-chromosome polymerase chain reaction (PCR) in sex-mismatched male BM plus
      female intestine or female BM plus male intestine transplantation into female
      recipients suggested that persistent macrochimerism was derived from infused BM.
      BM infusion together with lymphoid-depleted intestine grafts also supported
      macrochimerism development; however, third-party intestine grafts did not. After
      GFP-positive BM plus wild-type (WT) SITx into ACI, large numbers of GFP-positive
      leukocytes were found in WT intestine grafts. Isolated cells from WT intestine
      grafts developed GFP-positive CFU-Cs and propagated multilineage GFP-positive
      leukocytes when adoptively transferred into lethally irradiated WT recipients.
      These findings suggest that intestine allograft supports simultaneously infused
      donor (syngeneic to organ grafts) marrow stem cell engraftment, differentiation,
      and persistence of chimerism.

PMID- 16638930
TI  - Mcl-1L cleavage is involved in TRAIL-R1- and TRAIL-R2-mediated apoptosis induced
      by HGS-ETR1 and HGS-ETR2 human mAbs in myeloma cells.
AB  - We evaluated the ability of 2 human mAbs directed against TRAILR1 (HGS-ETR1) and
      TRAILR2 (HGS-ETR2) to kill human myeloma cells. HGS-ETR1 and HGS-ETR2 mAbs killed
      15 and 9 human myeloma cell lines (HMCLs; n = 22), respectively. IL-6, the major
      survival and growth factor for these HMCLs, did not prevent their killing.
      Killing induced by either HGS-ETR1 or HGS-ETR2 was correlated with the cleavage
      of Mcl-1L, a major molecule for myeloma survival. Mcl-1L cleavage and anti-TRAILR
      HMCL killing were dependent on caspase activation. Kinetic studies showed that
      Mcl-1L cleavage occurred very early (less than 1 hour) and became drastic once
      caspase 3 was activated. Our data showed that both the extrinsic (caspase 8, Bid)
      and the intrinsic (caspase 9) pathways are activated by anti-TRAIL mAb. Finally,
      we showed that the HGS-ETR1 and, to a lesser extent, the HGS-ETR2 mAbs were able
      to induce the killing of primary myeloma cells. Of note, HGS-ETR1 mAb was able to
      induce the death of medullary and extramedullary myeloma cells collected from
      patients at relapse. Taken together, our data clearly encourage clinical trials
      of anti-TRAILR1 mAb in multiple myeloma, especially for patients whose disease is
      in relapse, at the time of drug resistance.

PMID- 16638931
TI  - VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial
      storage compartment.
AB  - Endothelial cells respond to vascular endothelial growth factor (VEGF) to produce
      new blood vessels. This process of angiogenesis makes a critical contribution
      during embryogenesis and also in the response to ischemia in adult tissues. We
      have studied the intracellular trafficking of the major VEGF receptor KDR
      (VEGFR2). Unlike other related growth factor receptors, we find that a
      significant proportion of KDR is held in an endosomal storage pool within
      endothelial cells. We find that KDR can be delivered to the plasma membrane from
      this intracellular pool and that VEGF stimulates this recycling to the cell
      surface. KDR recycling appears to be distinct from the previously characterized
      Rab4- and Rab11-dependent pathways, but, instead, KDR(+) recycling vesicles
      contain Src tyrosine kinase and VEGF-stimulated recycling requires Src
      activation. Taken together, these data show that intracellular trafficking of KDR
      is markedly different from other receptor tyrosine kinases and suggest that the
      regulation of KDR trafficking by VEGF provides a novel mechanism for controlling
      the sensitivity of endothelial cells to proangiogenic signals.

PMID- 16638932
TI  - Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell
      recruitment.
AB  - Communication between endothelial cells (ECs) and mural cells is critical in
      vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may
      play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during
      vascular maturation. However, the molecular mechanism is unclear. We used
      microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an
      agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte
      growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1
      stimulation. We confirmed this finding by Northern blot and Western blot analyses
      in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1
      increased SMC migration toward endothelial cells in a coculture assay. Addition
      of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment,
      indicating that the induction of SMC migration by Ang1 was caused by the increase
      of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced
      HGF production and Ang1-induced SMC migration. Finally, we showed that deletion
      of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal
      a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and
      suggest that a delicate balance between Ang1 and Ang2 is critical in this
      process.

PMID- 16638933
TI  - Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal
      antigen-presenting cells.
AB  - Newborns are prone to microbial infection and have poor memory responses to
      multiple antigens. We have previously shown that human neonatal blood monocytes
      exhibit impaired TNF-alpha responses to most known TLR agonists, including the
      pure TLR7 agonist imiquimod. Surprisingly, however, neonatal TNF-alpha responses
      to the imiquimod congener R-848 (TLR 7/8) were fully intact. We now show that
      TLR8 agonists, including R-848 (TLR7/8), the imidazoquinoline congeners 3M-003
      (TLR7/8) and 3M-002 (TLR8), as well as single-stranded viral RNAs (TLR8) induced
      robust production of the Th1-polarizing cytokines TNF-alpha and IL-12 from
      neonatal antigen-presenting cells (APCs) that substantially exceeds responses
      induced by TLR-2, -4, or -7 (alone) agonists. TLR8 agonists also effectively
      induced up-regulation of the costimulatory molecule CD40 on neonatal and adult
      myeloid dendritic cells (DCs). The strong activity of TLR8 agonists correlates
      with their induction of p38 MAP kinase phosphorylation and with degradation of
      IkappaB-alpha in both neonatal and adult monocytes. We conclude that TLR8
      agonists are uniquely efficacious in activating costimulatory responses in
      neonatal APCs and suggest that these agents are promising candidate adjuvants for
      enhancing immune responses in human newborns.

PMID- 16638934
TI  - Alternating versus concurrent schedules of imatinib and chemotherapy as front
      line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
AB  - The best strategy for incorporating imatinib in front-line treatment of Ph+ acute
      lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients
      with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate
      sequentially 2 treatment schedules with imatinib administered concurrent to or
      alternating with a uniform induction and consolidation regimen. Coadministration
      of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR)
      rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of
      patients, compared with 19% in patients in the alternating treatment cohort (P =
      .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI)
      had similar hematologic and molecular responses after concurrent imatinib and
      INDII. In the concurrent cohort, grades III and IV cytopenias and transient
      hepatotoxicity necessitated interruption of induction in 87% and 53% of patients,
      respectively; however, duration of induction was not prolonged when compared with
      patients receiving chemotherapy alone. No imatinib-related severe hematologic or
      nonhematologic toxicities were noted with the alternating schedule. In each
      cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in
      first CR (CR1). Both schedules of imatinib have acceptable toxicity and
      facilitate SCT in CR1 in the majority of patients, but concurrent administration
      of imatinib and chemotherapy has greater antileukemic efficacy.

PMID- 16638935
TI  - Correction of a murine model of von Willebrand disease by gene transfer.
AB  - von Willebrand disease (VWD), the most common inherited bleeding disorder in the
      U.S. population, is caused by defects in the expression and processing of von
      Willebrand factor (VWF), a blood glycoprotein required for normal hemostasis that
      mediates the adhesion of platelets to sites of vascular damage by binding to
      specific platelet glycoproteins and to constituents of exposed connective tissue.
      To assess whether VWF deficiency can be corrected by gene transfer, a plasmid
      expressing the intact 8.4-kb murine VWF coding sequence, directed by the cyto
      megalovirus immediate/early promoter/enhancer, was delivered through hydrodynamic
      tail vein injection into VWF knockout mice (VWF(-/-)) that exhibit defects in
      hemostasis, including highly prolonged bleeding time and spontaneous bleeding
      events, closely mimicking severe human VWD. VWF antigen levels in plasma from
      animals receiving VWF cDNA, but not control animals, revealed normalized levels
      of circulating VWF that persisted for at least 1 week after injection. Western
      blot analysis of plasma from animals receiving VWF cDNA, but not control animals,
      revealed high molecular-weight multimers with patterns similar to those observed
      in wild-type mice. Reverse transcription-polymerase chain reaction (RT-PCR) on
      RNA isolated from the livers of animals receiving VWF cDNA, but not control
      animals, demonstrated that VWF was expressed in the liver, and
      immunohistochemical analysis of the livers of treated VWF(-/-) mice revealed VWF
      specific staining throughout the liver parenchyma but not in endothelial cells.
      Plasma from treated VWF(-/-) mice, but not control VWF(-/-) mice, supported the
      hypothesis that murine platelets aggregate in the presence of botrocetin.
      Although levels of circulating factor VIII in untreated VWF(-/-) mice were less
      than 10% those in wild-type mice, levels of factor VIII in VWF(-/-) animals
      treated with VWF cDNA, but not in control animals, were normalized to values in
      wild-type mice, indicating the restoration of factor VIII carrier function for
      VWF in treated mice that persisted for at least 1 week at higher doses of VWF
      cDNA. Most important, bleeding time was normalized by 48 hours after the delivery
      of VWF cDNA, but not by the control plasmid. These data suggest that with the use
      of gene transfer of VWF cDNA, VWF protein can be expressed, processed, and
      secreted in a physiologically active form; thus, it may be possible to correct
      VWD using gene transfer.

PMID- 16638936
TI  - Experts advise med guides for ADHD drugs.

PMID- 16638937
TI  - Shortages frustrate pediatric oncologists.

PMID- 16638938
TI  - Federal pharmacists adapt to changing environment.

PMID- 16638940
TI  - President promotes health savings accounts.

PMID- 16638941
TI  - Readability of brochure about phase-out of chlorofluorocarbons in metered-dose
      inhalers.

PMID- 16638942
TI  - Reducing medication errors by linking drug names with patients' diagnostic codes.

PMID- 16638943
TI  - Responding to Katrina: a Veterans Affairs pharmacist's experience.

PMID- 16638944
TI  - Educating providers and patients about Medicare Part D.

PMID- 16638945
TI  - Problems with health savings accounts.

PMID- 16638946
TI  - A distinctive competency.

PMID- 16638947
TI  - Safety of amiodarone in the prevention of postoperative atrial fibrillation: a
      meta-analysis.
AB  - PURPOSE: A meta-analysis was conducted to assess the safety of amiodarone in the
      prevention of postoperative atrial fibrillation. METHODS: A search of the medical
      literature was conducted to identify randomized controlled trials of prophylactic
      amiodarone use in cardiothoracic surgery. Studies were independently reviewed by
      three investigators and selected for inclusion if they met the following three
      criteria: (1) randomized controlled trial of amiodarone versus placebo or routine
      treatment, (2) patients underwent coronary artery bypass graft or valvular
      surgery, and (3) reported data on the frequency of at least one of the following
      safety endpoints: bradycardia, hypotension, heart block, nausea, cerebral
      vascular accident, myocardial infarction, and death. Both random- and fixed
      effects models were used to determine any significant associations between
      amiodarone and safety endpoints. RESULTS: Eighteen trials were analyzed. A total
      of 3408 patients were enrolled in these trials (1736 received amiodarone and 1672
      received placebo). Amiodarone increased the odds of developing bradycardia (odds
      ratio [OR], 1.70; 95% confidence interval [CI], 1.05-2.74) and hypotension (OR,
      1.62; 95% CI, 1.04-2.54). The administration of i.v. amiodarone, an average daily
      dose exceeding 1 g, and postoperative amiodarone administration were each
      associated with a greater likelihood of hemodynamic adverse effects. Amiodarone
      did not appear to affect other safety endpoints. CONCLUSION: Meta-analysis showed
      amiodarone to be associated with an increased risk of developing bradycardia and
      hypotension when used for the prophylaxis of postoperative atrial fibrillation.
      The greatest risk in the occurrence of these adverse events arose when using
      regimens containing i.v. amiodarone, initiating prophylaxis during the
      postoperative period, and using regimens with average daily doses exceeding 1 g.

PMID- 16638948
TI  - Ability of practitioners to identify solid oral dosage tablets.
AB  - PURPOSE: Physicians' and pharmacists' ability to correctly identify three
      commonly used oral dosage forms was assessed. METHODS: A list of physicians and
      pharmacists was obtained from two urban teaching hospitals. A total of 100
      pharmacists and physicians were randomly selected and their ability to correctly
      identify three commonly used tablets was tested. Participants were also asked
      about their experiences and views on current resources and alternatives for
      identifying oral dosage forms. Tablet-identification exercises were performed by
      physicians and pharmacists in their usual practice settings. Participants could
      consult the resources usually available to them for the identification of unknown
      medications. RESULTS: A total of 300 observations were made in the tablet
      identification exercise (100 participants, three tablets per participant). The
      tablet was correctly identified in 190 of the observations (63%). The brand-name
      tablet, the generic tablet, and the nonprescription generic tablet were correctly
      identified in 78%, 64%, and 48% of the observations, respectively. Only 18
      physicians (36%) and 24 pharmacists (48%) correctly identified all three tablets,
      whereas 10 physicians (20%) and 5 pharmacists (10%) could not correctly identify
      any of the tablets. The mean time required to identify a tablet was 3.65 minutes.
      Pharmacists most often used electronic resources (52%), while physicians relied
      on print resources. Overall, 77% expressed dissatisfaction with the current
      system and 91% favored a universal imprint coding system for oral dosage forms.
      CONCLUSION: Physicians and pharmacists failed to correctly identify three
      commonly prescribed tablets more than a third of the time. The brand-name tablet
      was correctly identified more often than were the prescription generic and
      nonprescription generic products.

PMID- 16638950
TI  - Home treatment for intensive hematological therapies: who will benefit?

PMID- 16638951
TI  - St Gallen guidelines: aromatase inhibitors recommended by name for adjuvant
      therapy.

PMID- 16638952
TI  - Prothrombin time testing practices: adherence to guidelines and standards.

PMID- 16638953
TI  - Will the real myocardial infarction please stand up?

PMID- 16638954
TI  - Adiponectin: a promising marker for cardiovascular disease.

PMID- 16638955
TI  - Effects of blood collection tubes, including pediatric devices, on 16 common
      immunoassays.

PMID- 16638957
TI  - How reliable are critical error calculations?

PMID- 16638956
TI  - ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack
      of association with side effects and therapeutic response in depressed inpatients
      treated with amitriptyline.

PMID- 16638958
TI  - Characterization of interference with 6 commercial delta9-tetrahydrocannabinol
      immunoassays by efavirenz (glucuronide) in urine.

PMID- 16638959
TI  - Metabolic syndrome: older than usually assumed, but still too young to die.

PMID- 16638961
TI  - Validation of a rapid, simple method to measure alpha1-antitrypsin in human dried
      blood spots.

PMID- 16638962
TI  - Prenatal diagnosis of the WAS R86H sequence variation in heterozygous twins.

PMID- 16638963
TI  - Comparison of 3 third-generation assays for bio-intact parathyroid hormone.

PMID- 16638964
TI  - Adsorption of mycophenolic acid and its phenolic glucuronide to glass,
      polystyrene, and polypropylene containers.

PMID- 16638965
TI  - Lack of utility of free light chain-specific antibodies in the urine
      immunofixation test.

PMID- 16638966
TI  - Liquid chromatographic determination of B(2) vitamers in human plasma and whole
      blood.

PMID- 16638967
TI  - Prolonged dormancy of human liposarcoma is associated with impaired tumor
      angiogenesis.
AB  - The disease state of cancer appears late in tumor development. Before being
      diagnosed, a tumor can remain for prolonged periods of time in a dormant state.
      Dormant human cancer is commonly defined as a microscopic tumor that does not
      expand in size and remains asymptomatic. Dormant tumors represent an early stage
      in tumor development and may therefore be a potential target for nontoxic,
      antiangiogenic therapy that could prevent tumor recurrence. Here, we characterize
      an experimental model that recapitulates the clinical dormancy of human tumors in
      mice. We demonstrate that these microscopic dormant cancers switch to the
      angiogenic phenotype at a predictable time. We further show that while angiogenic
      liposarcomas expand rapidly after inoculation of tumor cells in mice,
      nonangiogenic dormant liposarcomas remain microscopic up to one-third of the
      normal severe combined immune deficiency (SCID) mouse life span, although they
      contain proliferating tumor cells. Nonangiogenic dormant tumors follow a similar
      growth pattern in subcutaneous (s.c.) and orthotopic environments. Throughout the
      dormancy period, development of intratumoral vessels is impaired. In nonangogenic
      dormant tumors, small clusters of endothelial cells without lumens are observed
      early after tumor cell inoculation, but the nonangiogenic tumor cannot sustain
      these vessels, and they disappear within weeks. There is a concomitant decrease
      in microvessel density, and the nonangiogenic dormant tumor remains harmless to
      the host. In contrast, microvessel density in tumors increases rapidly after the
      angiogenic switch and correlates with rapid expansion of tumor mass. Both tumor
      types cultured in vitro contain fully transformed cells, but only cells from the
      nonangiogenic human liposarcoma secrete relatively high levels of the
      angiogenesis inhibitors thrombospondin-1 and TIMP-1. This model suggests that as
      improved blood or urine molecular biomarkers are developed, the microscopic,
      nonangiogenic, dormant phase of human cancer may be vulnerable to antiangiogenic
      therapy years before symptoms, or before anatomical location of a tumor can be
      detected, by conventional methods.

PMID- 16638968
TI  - Retinoic acids increase P2X2 receptor expression through the 5'-flanking region
      of P2rx2 gene in rat phaeochromocytoma PC-12 cells.
AB  - The P2X2 receptor is a subtype of ionotropic ATP receptor and plays a significant
      role in regulating fast synaptic transmission in the nervous system. Because the
      expression level of the P2X2 receptor is known to determine its channel
      properties and functional interactions with other neurotransmitter channels,
      elucidating the mechanisms underlying the regulation of P2X2 receptor expression
      in neuronal cells is important. Here, we identified three motifs that correspond
      to the retinoic acid response element in the 5'-flanking region of the rat P2X2
      gene. In rat pheochromocytoma PC-12 cells, treatment with 9-cis-retinoic acid as
      well as all-trans-retinoic acid significantly increased the mRNA and protein
      level of P2X2 receptor. In addition, in PC-12 cells transiently transfected with
      a luciferase reporter gene driven by the promoter region of the rat P2X2 gene,
      both 9-cis-retinoic acid and all-trans-retinoic acid increased the luciferase
      activity, whereas their effects were diminished by truncation of the retinoic
      acid response elements in the promoter. Furthermore, 9-cis-retinoic acid enhanced
      the ATP-evoked whole cell currents and intracellular Ca2+- and ATP-evoked
      dopamine release, indicating the up-regulation of functional P2X2 receptors on
      the plasma membrane. These results provide the molecular mechanism underlying the
      transcriptional regulation of P2X2 receptors and suggest that retinoid is an
      important factor in regulating P2X2 receptors in the nervous system.

PMID- 16638969
TI  - Estrogens cross-talk to alpha1b-adrenergic receptors.
AB  - beta-Estradiol induced alpha1b-adrenergic receptor desensitization in U373 MG
      cells stably expressing alpha1b-adrenoceptors, as evidenced by a reduction in the
      adrenergic-mediated Ca2+ mobilization; desensitization was associated with
      receptor phosphorylation and internalization. These effects of beta-estradiol
      were rapid (taking place during 15 min) and were blocked by the estrogen receptor
      antagonist ICI 182,780 (faslodex). Likewise, inhibitors of phosphoinositide 3
      kinase [wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
      (LY294002)] and of protein kinase C [staurosporine, 3-[1-[3-(amidinothio)propyl
      1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl) maleimide (Ro31-8220), and rottlerin]
      blocked the desensitization and phosphorylation of alpha1b-adrenoceptors induced
      by estradiol. The formation of a complex was suggested by coimmunoprecipitation
      assays. The regulatory and catalytic subunits of phosphoinositide 3-kinase (p85
      and p110) and protein kinase C delta were associated with alpha1b-adrenoceptors
      in the absence of stimulus, and such association further increased in a dynamic
      fashion in response to beta-estradiol. In cells cotransfected with the estrogen
      receptor alpha and alpha1b-adrenoceptors, beta-estradiol induced phosphorylation,
      desensitization and internalization of the adrenergic receptors; pretreatment
      with ICI 182,780 inhibited these effects. Our data support the idea that
      estrogens modulate alpha1b-adrenergic action through estrogen receptor alpha.

PMID- 16638970
TI  - ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family:
      characterization of transporter properties.
AB  - Cadmium is a dangerous metal distributed widely in the environment. Members of
      our laboratory recently identified the ZIP8 transporter protein, encoded by the
      mouse Slc39a8 gene, to be responsible for genetic differences in response to
      cadmium damage of the testis. Stable retroviral infection of the ZIP8 cDNA in
      mouse fetal fibroblast cultures (rvZIP8 cells) leads to as much as a 10-fold
      increase in the rate of intracellular cadmium influx and accumulation. In the
      present study, we showed that cadmium uptake operated maximally at pH 7.5 and a
      temperature of 37 degrees C and was inhibited by cyanide. Of more than a dozen
      cations tested, manganese(II) was the best competitive cation for cadmium uptake.
      The Km for Cd2+ uptake was 0.62 microM, and the Km for Mn2+ uptake was 2.2
      microM; thus, manganese is probably the physiological substrate for ZIP8. Cadmium
      uptake was independent of sodium, potassium or chloride ions, but strongly
      dependent on the presence of bicarbonate. By Western blot analysis of rvZIP8
      cells, we showed that ZIP8 protein was glycosylated. Using Z-stack confocal
      microscopy in Madin-Darby canine kidney polarized epithelial cells, we found that
      ZIP8 was localized on the apical side-implying an important role for manganese or
      cadmium uptake and disposition. It is likely that ZIP8 is a Mn2+/HCO3- symporter,
      that a HCO3- gradient across the plasma membrane acts as the driving force for
      manganese uptake, and that cadmium is a rogue hitchhiker displacing manganese to
      cause cadmium-associated disease.

PMID- 16638971
TI  - Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated
      sodium channels is determined by the pore loop of domain 3.
AB  - Voltage-gated sodium (Nav) channels are modulated by a variety of specific
      neurotoxins. Scorpion beta-toxins affect the voltage-dependence of channel
      gating: In their presence, Nav channels activate at subthreshold membrane
      voltages. Previous mutagenesis studies have revealed that the beta-toxin Css4
      interacts with the extracellular linker between segments 3 and 4 in domain 2 of
      Nav channels with the effect to trap this voltage sensor in an open position
      (Neuron 21: 919-931, 1998 ). The voltage sensor of domain 2 was thus identified
      to constitute a major part of neurotoxin receptor site 4. In this work, we
      studied the effects of the beta-toxin Tz1 from the Venezuelan scorpion Tityus
      zulianus on various mammalian Nav channel types expressed in HEK 293 cells.
      Although skeletal muscle channels (Nav1.4) were strongly affected by Tz1, the
      neuronal channels Nav1.6 and Nav1.2 were less sensitive, and the cardiac Nav1.5
      and the peripheral nerve channel Nav1.7 were essentially insensitive. Analysis of
      channel chimeras in which whole domains of Nav1.2 were inserted into a Nav1.4
      background revealed that the Nav1.2 phenotype was not conferred to Nav1.4 by
      domain 2 but by domain 3. The interaction epitope could be narrowed down to
      residues Glu1251, Lys1252, and His1257 located in the C-terminal pore loop in
      domain 3. The receptor site for beta-toxin interaction with Nav channels thus
      spans domains 2 and 3, where the pore loop in domain 3 specifies the
      pharmacological properties of individual neuronal Nav channel types.

PMID- 16638972
TI  - Direct modulation of phospholipase D activity by Gbetagamma.
AB  - Phospholipase D-mediated hydrolysis of phosphatidylcholine is stimulated by
      protein kinase C and the monomeric G proteins Arf, RhoA, Cdc42, and Rac1,
      resulting in complex regulation of this enzyme. Using purified proteins, we have
      identified a novel inhibitor of phospholipase D activity, Gbetagamma subunits of
      heterotrimeric G proteins. G protein-coupled receptor activation alters affinity
      between Galpha and Gbetagamma subunits, allowing subsequent interaction with
      distinct effectors. Gbeta1gamma1 inhibited phospholipase D1 and phospholipase D2
      activity, and both Gbeta1gamma1 and Gbeta1gamma2 inhibited stimulated
      phospholipase D1 activity in a dosedependent manner in reconstitution assays.
      Reconstitution assays suggest this interaction occurs through the amino terminus
      of phospholipase D, because Gbeta1gamma1 is unable to inhibit an amino-terminally
      truncated phospholipase D construct, PLD1.d311, which like full-length
      phospholipase D isoforms, requires phosphatidylinositol-4,5-bisphosphate for
      activity. Furthermore, a truncated protein consisting of the amino-terminal
      region of phospholipase D containing the phox/pleckstrin homology domains was
      found to interact with Gbeta1gamma1, unlike the PLD1.d311 recombinant protein,
      which lacks this domain. In vivo, expressed recombinant Gbeta1gamma2 was also
      found to inhibit phospholipase D activity under basal and stimulated conditions
      in MDA-MB-231 cells, which natively express both phospholipase D1 and
      phospholipase D2. These data demonstrate that Gbetagamma directly regulates
      phospholipase D activity in vitro and suggest a novel mechanism to negatively
      regulate phospholipase D signaling in vivo.

PMID- 16638973
TI  - Research opportunities in vision: a report of the U.S.-Indo workshops on
      collaborative research.

PMID- 16638977
TI  - The epidemiology of eye disease: from glycemia to genetics: the Friedenwald
      Lecture.

PMID- 16638975
TI  - Eye cancer: unique insights into oncogenesis: the Cogan Lecture.

PMID- 16638979
TI  - The balance between corneal transparency and edema: the Proctor Lecture.

PMID- 16638980
TI  - Change in the synthesis rates of ocular retinoic acid and scleral
      glycosaminoglycan during experimentally altered eye growth in marmosets.
AB  - PURPOSE: The purpose of this study was to examine the possibility that all-trans
      retinoic acid (RA) in the eye is a signal related to changes in scleral
      extracellular matrix in a primate model of postnatal eye growth. METHODS:
      Juvenile marmosets (Callithrix jacchus) were divided into two experimental groups
      based on their response to monocular deprivation with diffusers: group 1, treated
      eyes becoming longer than fellow control eyes (n = 8), and group 2, treated eyes
      becoming shorter than control eyes (n = 7). Eyes were enucleated, dissected, and
      assayed for changes in the rates of scleral glycosaminoglycan (GAG) synthesis and
      ocular RA synthesis. The rate of incorporation of (35)SO4 into CPC-precipitable
      GAG in scleras was taken as a measure of the rate of synthesis of proteoglycans.
      In the same eyes the rate of RA synthesis in vivo was measured separately in the
      retina and the choroid/RPE (choroid with RPE attached) by HPLC. The effect of RA
      on the rate of scleral GAG synthesis was also examined in tissue-cultured pieces
      of sclera from additional marmosets. RESULTS: Induced changes in vitreous chamber
      length in diffuser-treated eyes correlated inversely with the rate of scleral GAG
      synthesis (P < 0.05) and directly correlated with the rate of RA synthesis
      measured separately in the retina (P < 0.05) and the choroid/RPE (P < 0.05). In
      group 1, the rate of scleral GAG synthesis was significantly lower (P < 0.01) in
      the treated eyes relative to control eyes, and the rate of RA synthesis in both
      the retina and the choroid/RPE was significantly higher (P < 0.01). In group 2,
      the rates of scleral GAG synthesis and RA synthesis in either the retina or
      choroid/RPE were not found to change significantly in the treated eyes compared
      with the control eyes. RA partially reduces the rate of scleral GAG synthesis in
      tissue-cultured primate sclera in a dose-dependent manner after several days.
      CONCLUSIONS: RA may play a role in the visual control of postnatal eye growth in
      primates, possibly by inducing changes in scleral extracellular matrix associated
      with increasing eye size. Decreasing growth rate below control levels may involve
      other mechanisms.

PMID- 16638981
TI  - The relation of axial length and intraocular pressure fluctuations in human eyes.
AB  - PURPOSE: To determine in human eyes whether diurnal fluctuations in axial length
      are related to fluctuations in intraocular pressure (IOP) by studying these
      fluctuations in both eyes of individual subjects and by assessing the regularity
      of both rhythms on two separate study days. METHODS: Ten subjects, ages 18 to 24
      years, underwent serial axial length and IOP measurements using highly precise,
      noncontact partial coherence interferometry and Goldmann applanation tonometry,
      respectively. Both eyes were measured at six 3-hour intervals during each of two
      study days, and significant fluctuations were modeled by sine curves. RESULTS: Of
      the 40 data sets, 29 had significant axial length high-low differences and 32 had
      significant IOP high-low differences (ANOVA, P < 0.05 for each). The magnitude of
      the significant high-low differences were 38 +/- 22 microm for axial length and
      6.0 +/- 1.9 mm Hg for IOP (mean +/- SD). Neither axial length nor IOP
      fluctuations necessarily occurred bilaterally on the same day, and neither rhythm
      was regularly observed on two separate days in individual eyes. In eyes in which
      both parameters fluctuated on the same day, there were no correlations in the
      amplitude, period or phase of the two rhythms. CONCLUSIONS: Both axial length and
      IOP fluctuate during the day much of the time in most subjects. However, diurnal
      IOP fluctuations do not appear to cause diurnal axial length fluctuations.

PMID- 16638982
TI  - Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene
      dose.
AB  - PURPOSE: PITX2 gene dose plays a central role in Axenfeld-Rieger syndrome. The
      purpose of this study was to test the hypothesis that the effects of Pitx2 gene
      dose on eye development can be molecularly dissected in available Pitx2 mutant
      mice. METHODS: A panel of mice with Pitx2 gene dose ranging from wild-type (+/+)
      to none (-/-) was generated. Eye morphogenesis was assessed in animals with each
      Pitx2 gene dose. We also compared global gene expression in eye primordia taken
      from e12.5 Pitx2+/+, Pitx2+/-, Pitx2-/- embryos using gene microarrays. The
      validity of microarray results was confirmed by qRT-PCR. RESULTS: Morphogenesis
      of all extraocular muscle bundles correlated highly with Pitx2 gene dose, but
      there were some differences in sensitivity among muscle groups. Superior and
      inferior oblique muscles were most sensitive and disappeared before the four
      rectus muscles. Expression of muscle-specific genes was globally sensitive to
      Pitx2 gene dose, including the muscle-specific transcription factor genes Myf5,
      Myog, Myod1, Smyd1, Msc, and Csrp3. CONCLUSIONS: Pitx2 gene dose regulates both
      morphogenesis and gene expression in developing extraocular muscles. The
      expression of key muscle-specific transcription factor genes is regulated by
      Pitx2 gene dose, suggesting that sufficient levels of PITX2 protein are essential
      for early initiation of the myogenic regulatory cascade in extraocular muscles.
      These results document the first ocular tissue affected by Pitx2 gene dose in a
      model organism, where the underlying mechanisms can be analyzed, and provide a
      paradigm for future experiments designed to elucidate additional effects of Pitx2
      gene dose during eye development.

PMID- 16638983
TI  - Differential gene expression in mouse sclera during ocular development.
AB  - PURPOSE: Ocular development involves changes in extracellular matrix components
      of the scleral wall as it expands. This study was conducted to determine scleral
      gene expression profiles during mouse ocular development to identify genes
      involved in normal scleral growth. METHODS: Sample sets of pooled sclerae of 3-
      and 8-week-old mice were microdissected, and total RNA was isolated. After
      reverse transcription, the cDNA was in vitro transcribed to produce biotin
      labeled cRNA. The purified biotin-labeled cRNA samples were hybridized to
      microarray chips (GeneChip Mouse Genome 430 2.0; Affymetrix, Santa Clara, CA).
      Gene transcript expression profiles were determined, and eight differentially
      expressed genes between the two age groups underwent further confirmation by real
      time PCR analysis. RESULTS: Differential regulation of 4884 gene transcripts in
      mouse sclera with less than 5% false-discovery rate (FDR) was identified. The top
      1000 with the lowest FDR among the 4884 probe sets were filtered for threefold
      changes between the two age groups, and 718 gene transcripts were identified.
      Among these 718 gene transcripts, 210 were upregulated and 508 downregulated in
      adult relative to juvenile mouse sclera. TGF-beta1 and several collagen genes
      were significantly downregulated. Microarray differential expression by real-time
      PCR validation of eight extracellular matrix-associated gene transcripts was
      confirmed. CONCLUSIONS: This is the first study to demonstrate gene expression
      profiles in mouse sclera during ocular growth. These findings support the role of
      TGFbeta1 as a signaling molecule in modulating extracellular matrix during ocular
      development. This endeavor may be helpful in furthering understanding of how
      scleral remodeling is regulated during eye growth.

PMID- 16638984
TI  - Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with
      Axenfeld-Rieger syndrome with developmental glaucoma.
AB  - PURPOSE: Axenfeld-Rieger (AR) is an autosomal dominant disorder with phenotypic
      heterogeneity characterized by anterior segment dysgenesis, facial bone defects,
      and redundant periumbilical skin. The PITX2 gene, on chromosome 4q25, and the
      FOXC1 gene, on chromosome 6p25, have been implicated in the different phenotypes
      of the syndrome through mutational events. Recently, the CYP1B1 gene was found to
      be associated with Peters' anomaly, and the gene associated with
      oculodentodigital dysplasia syndrome, which presents some similarities with AR,
      was identified (connexin 43--GJA1 gene). The purpose of this study was to
      evaluate PITX2, FOXC1, CYP1B1, and GJA1 gene mutations in Brazilian families with
      AR. METHODS: Eight unrelated patients affected by AR (all eight with glaucoma and
      three with systemic manifestations) and their families were ophthalmologically
      evaluated and their blood was collected for DNA extraction purposes. The coding
      regions of PITX2, FOXC1, CYP1B1, and GJA1 genes were completely evaluated through
      direct sequencing. RESULTS: The frequency of mutations in the FOXC1, GJA1, PITX2,
      and CYP1B1 genes in this study were 25%, 12.5%, 0% and 0%, respectively. In the
      FOXC1 gene, two GGC triplet insertions (GGC375ins and GGC447ins) defined as a
      polymorphism, and two new mutations--a deletion (718 to 719delCT) and a nonsense
      mutation (Trp152STOP)--were identified. One polymorphism (Ala253Val) was
      identified in the GJA1 gene in the same family presenting the Trp152STOP mutation
      in the FOXC1 gene. In this family harboring both structural alterations, two
      patients who carried the GJA1 (Ala253Val) and FOXC1 (Trp152STOP) mutations
      developed less severe glaucoma compared with family members presenting the FOXC1
      (Trp152STOP) mutation alone. CONCLUSIONS: Two new structural alterations in the
      FOXC1 gene and a polymorphism in the GJA1 gene were first described in Brazilian
      patients with AR and developmental glaucoma. A polymorphism in the GJA1 gene
      (Ala253Val), for the first time identified in association with AR, raises the
      possibility of its participation as a modifier gene.

PMID- 16638985
TI  - Differential mitochondrial DNA and gene expression in inherited retinal dysplasia
      in miniature Schnauzer dogs.
AB  - PURPOSE: To investigate the molecular basis of inherited retinal dysplasia in
      miniature Schnauzers. METHODS: Retina and retinal pigment epithelial tissues were
      collected from canine subjects at the age of 3 weeks. Total RNA isolated from
      these tissues was reverse transcribed to make representative cDNA pools that were
      compared for differences in gene expression by using a subtractive hybridization
      technique referred to as representational difference analysis (RDA). Expression
      differences identified by RDA were confirmed and quantified by real-time reverse
      transcription PCR. Mitochondrial morphology from leukocytes and skeletal muscle
      of normal and affected miniature Schnauzers was examined by transmission electron
      microscopy. RESULTS: RDA screening of retinal pigment epithelial cDNA identified
      differences in mRNA transcript coding for two mitochondrial (mt) proteins-
      cytochrome oxidase subunit 1 and NADH dehydrogenase subunit 6--in affected dogs.
      Contrary to expectations, these identified sequences did not contain mutations.
      Based on the implication of mt-DNA-encoded proteins by the RDA experiments we
      used real-time PCR to compare the relative amounts of mt-DNA template in white
      blood cells from normal and affected dogs. White blood cells of affected dogs
      contained less than 30% of the normal amount of two specific mtDNA sequences,
      compared with the content of the nuclear-encoded glyceraldehyde-3-phosphate
      dehydrogenase (GA-3-PDH) reference gene. Retina and RPE tissue from affected dogs
      had reduced mRNA transcript levels for the two mitochondrial genes detected in
      the RDA experiment. Transcript levels for another mtDNA-encoded gene as well as
      the nuclear-encoded mitochondrial Tfam transcription factor were reduced in these
      tissues in affected dogs. Mitochondria from affected dogs were reduced in number
      and size and were unusually electron dense. CONCLUSIONS: Reduced levels of
      nuclear and mitochondrial transcripts in the retina and RPE of miniature
      Schnauzers affected with retinal dysplasia suggest that the pathogenesis of the
      disorder may arise from a lowered energy supply to the retina and RPE.

PMID- 16638986
TI  - Functional field score: the effect of using a Goldmann V-4e isopter instead of a
      Goldmann III-4e isopter.
AB  - PURPOSE: To investigate the underestimation of field loss in functional field
      score (FFS) between the Goldmann isopters III-4e and V-4e in visually impaired
      patients, in order to develop a predictive model for the FFS(III-4e) based on
      FFS(v-4e) that adjusts for possible confounders. Although the visual field is
      generally evaluated using Goldmann isopter III-4e, it has the disadvantage that
      not all low-vision patients are able to see the stimulus corresponding to this
      isopter. METHODS: Goldmann visual fields were obtained from 58 patients with a
      variety of eye diseases. Eligibility criteria were age of 18 years or older and
      valid results of a Goldmann III-4e and V-4e visual field test in at least one
      eye. Linear regression was used to develop the model, setting FFS(III-4e) as the
      dependent variable and FFS(V-4e) as the independent one. RESULTS: The FFS(V-4e)
      was higher than the FFS(III-4e), the mean difference being 14.56 points (95% CI,
      12.48 -16.64). Multiple linear regression analysis showed that age, functional
      acuity score, primary eye disease, and central-peripheral loss were not
      confounders for the prediction of FFS(III-4e). FFS(III-4e) was estimated with the
      following equation: FFS(III-4e) = -19.25 + 1.063 x FFS(V-4e). CONCLUSIONS: The
      relationship between FFS(III-4e) and FFS(V-4e) is linear, and the FFS(V-4e) can
      be used to estimate the FFS(III-4e). In practice, just subtracting 19.25 points
      of the value of FFS(V-4e) will be sufficient to estimate the value of FFS(III
      4e). This model should give confidence about using the bigger isopter for
      determining the visual impairment of a person by the FFS.

PMID- 16638987
TI  - Accommodative dysfunction in children with cerebral palsy: a population-based
      study.
AB  - PURPOSE: To determine the prevalence, nature, and degree of accommodative
      dysfunction among children with different types and severities of cerebral palsy
      (CP) in Northern Ireland. METHODS: Ninety subjects with CP (aged 4-15 years) were
      recruited through the Northern Ireland CP Register (NICPR). Modified Nott dynamic
      retinoscopy was used to measure lag and lead of accommodation at three test
      distances: 25 cm (4 D), 16.7 cm (6 D), and 10 cm (10 D) with the distance
      correction in place. Accommodative function was also assessed in an age-matched
      control group (n = 125) for comparison. Each subject's neurologic status was
      derived from the NICPR. RESULTS: Children with CP demonstrate significantly
      reduced accommodative responses compared with their neurologically normal peers.
      Of the subjects with CP, 57.6% demonstrated an accommodative lag outside normal
      limits at one or more distances. Reduced accommodative responses were
      significantly associated with more severe motor and intellectual impairments
      (ANOVA P = 0.001, P < 0.01, respectively). CONCLUSIONS: Brain injury such as that
      present in CP has a significant impact on accommodative function. These findings
      have implications for the optometric care of children with CP and inform our
      understanding of the impact of early brain injury on visual development.

PMID- 16638988
TI  - How evidence-based are publications in clinical ophthalmic journals?
AB  - PURPOSE: To evaluate the methodological quality and level of evidence of
      publications in four leading general clinical ophthalmology journals. METHODS:
      All 1919 articles published in the American Journal of Ophthalmology, Archives of
      Ophthalmology, British Journal of Ophthalmology, and Ophthalmology in 2004 were
      reviewed. The methodological rigor and the level of evidence in the articles were
      rated according to the McMaster Hedges Project criteria and the Oxford Centre for
      Evidence-Based Medicine levels of evidence. RESULTS: Overall, 196 (24.4%) of the
      804 publications that were included for assessment met the Hedges criteria.
      Articles on economics evaluation and those on prognosis achieved the highest
      passing rate, with 80.0% and 74.4% of articles, respectively, meeting the Hedges
      criteria. Publications on etiology, diagnosis, and treatment fared less well,
      with respective passing rates of 28.3%, 20.2%, and 14.7%. Published systematic
      reviews and randomized controlled trials were uncommon in the ophthalmic
      literature, at least in these four journals during 2004. According to the Oxford
      criteria, 57.6% of the articles were classified as level 4 evidence compared with
      18.1% classified as level 1. Articles on prognosis had the highest proportion
      (43.0%) rated as level 1 evidence. Generally, articles that reached the Hedges
      threshold were rated higher on the level-of-evidence scale (Spermans rho = 0.73;
      P < 0.001). CONCLUSIONS: The methodological quality of publications in the
      clinical ophthalmic literature was comparable to that in the literature of other
      specialties. There was substantial heterogeneity in quality between different
      types of articles. Future methodological improvements should focus on the areas
      identified as having the largest deficiencies.

PMID- 16638989
TI  - A cohort study of incident myopia in Singaporean children.
AB  - PURPOSE: To determine the risk factors of incident myopia in a school-based
      cohort study in Singaporean children. METHODS: A 3-year prospective cohort study
      was conducted in Singaporean school children aged 7 to 9 years in three schools
      at entry. Chinese children without myopia at baseline (n = 994) were included in
      the analysis. The main outcome was incident myopia, defined as spherical
      equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other
      definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also
      assessed. RESULTS: After controlling for school, age, gender, income, reading in
      books per week and intelligence quotient (IQ) test scores, we found the relative
      risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence
      interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of
      myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89).
      However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit
      increase in books read per week. Similar results were obtained with definitions
      of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new
      prospective evidence of essential links between parental myopia, IQ scores and
      subsequent myopia development. However, reading in books per week was not
      associated with incident myopia.

PMID- 16638990
TI  - Myopic refractive error in adult Latinos: the Los Angeles Latino Eye Study.
AB  - PURPOSE: To estimate gender- and age-specific prevalence of myopia and identify
      risk indicators for myopia in a population-based sample of Latino adults aged 40
      years and older in La Puente, California. METHODS: Noncycloplegic automated
      refraction with supplemental standardized subjective refraction was performed for
      presenting visual acuity worse than 20/20. Potential risk indicators for myopia
      were evaluated by questionnaire and clinical examination. The gender- and age
      specific prevalence of spherical equivalent myopia in phakic eyes was calculated.
      Multiple logistic regression identified independent risk indicators for myopia.
      RESULTS: Refractive error was analyzed for the worse eye of 5927 of 6357
      participating Latinos. The overall prevalence of myopia < or = -1.0 D was 16.8%,
      and of high myopia < or = -5.0 D, 2.4%. When participants were stratified by age,
      myopia initially decreased with age and then increased in the oldest groups in
      association with nuclear opacification. Risk indicators for myopia were: oldest
      and youngest age groups, presence of diabetes mellitus, high acculturation, high
      school or higher education, and birth in the United States. The latter two were
      also predictors of high myopia. CONCLUSIONS: Risk indicators for myopia in adult
      Latinos include higher education, birth in the United States, high acculturation,
      and diabetes. The burden of myopia in older Latinos exceeds that in African
      Americans and non-Hispanic whites in the United States.

PMID- 16638991
TI  - Adhesion structures of amniotic membranes integrated into human corneas.
AB  - PURPOSE: The aim of this study was to investigate the structural relationship
      between integrated amniotic membrane (AM) and corneal tissues in various
      integration patterns, focusing on adhesion structures along the interface.
      METHODS: Fourteen eyes of 14 patients (age, 65.8 +/- 13.5 years) underwent
      penetrating keratoplasty (PKP) 19.3 +/- 20.7 weeks after cryopreserved human AM
      transplantation (AMT). The corneal buttons (after PKP) and the corresponding
      original AM (before AMT) were examined with the use of transmission electron
      microscopy (TEM) and immunohistochemistry for integrin beta4, type VII collagen,
      and laminin. Main outcome measures included thickness of the corneal epithelium
      and AM, density of the epithelial desmosomes and hemidesmosomes, continuity, and
      thickness of the epithelial basement membrane. RESULTS: Integrated AM was found
      by slit lamp in only 2 of 14 patients, but histology and TEM revealed AM
      integration in 11 of 14 patients up to 77 weeks after AMT. No amniotic epithelial
      cell was detected in any cornea with integrated AM stroma. Three basic patterns
      of integration could be described: subepithelial, intraepithelial, and
      intrastromal. Hemidesmosomes anchored the corneal epithelial cells to the AM at a
      density up to 165.3 +/- 22.9 per 100 microm cell membrane length. Discontinuous
      basement membrane segments 17.2 +/- 4.9 nm thick could be detected. Desmosomes
      among recovered corneal epithelial cells were found at a density of 21.2 +/- 5.3
      per 10 microm cell membrane length. CONCLUSIONS: The AM stroma can integrate into
      the host corneal tissue. Integration is associated with the formation of adhesion
      structures such as hemidesmosomes and desmosomes, which provide anchoring and
      stability of the regenerating corneal epithelium. The presence of integrated AM
      and adhesion structures with host corneal tissue supports the clinical experience
      obtained with AMT in ocular surface disease.

PMID- 16638992
TI  - Promotion of corneal epithelial wound healing in vitro and in vivo by annexin A5.
AB  - PURPOSE: To investigate the effect of annexin A5, a calcium-dependent
      phospholipid-binding protein, on corneal epithelial wound healing. METHODS: The
      effect of annexin A5 on migration of rabbit corneal epithelial (RCE) cells in
      vitro was examined in scrape-wounded cell monolayers. The effect of annexin A5 on
      the release of urokinase-type plasminogen activator (uPA) from cultured RCE cells
      was determined by zymography, fluorogenic assay of PA activity, and enzyme-linked
      immunosorbent assay. The proliferation of RCE cells was assessed by measurement
      of [3H]thymidine incorporation. The effect of annexin A5 on corneal wound closure
      in rabbits was investigated after removal of the corneal epithelium, either by
      exposure to iodine vapor or surgically. Eye drops containing annexin A5 were
      instilled into one eye and vehicle into the other. The area of the epithelial
      defect was measured at various times after wounding, and the healing rate was
      calculated by linear regression analysis. RESULTS: Annexin A5 significantly
      promoted the migration of RCE cells in a wounded monolayer. However, annexin A5
      had no effect on RCE cell proliferation. Annexin A5 also increased the release of
      uPA both from wounded RCE cell monolayers and from nonwounded semiconfluent RCE
      cells. In both models of corneal wound closure, the healing rate was
      significantly increased by instillation of eye drops containing annexin A5
      compared with that apparent in the eyes that received vehicle. CONCLUSIONS:
      Annexin A5 promoted corneal epithelial wound healing both in vitro and in vivo.
      Upregulation of uPA release from corneal epithelial cells may contribute to this
      effect of annexin A5.

PMID- 16638993
TI  - A simple, cross-linked collagen tissue substitute for corneal implantation.
AB  - PURPOSE: To develop a simple corneal substitute from cross-linked collagen.
      METHODS: Porcine type I collagen (10%; pH 5), was mixed with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final
      homogenous solution was molded to corneal dimensions, cured, and then implanted
      into rabbits and minipigs by lamellar keratoplasty. The implants were followed
      for up to 6 months after surgery. Clinical examinations of the cornea included
      detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and
      esthesiometry for nerve function. Histopathologic examinations were also
      performed on rabbit corneas harvested after 6 months. RESULTS: Cross-linked
      collagen (refractive index, 1.35) had optical clarity superior to human corneas.
      Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas
      showed a slight haze at 6 months after surgery. All other implants showed no
      adverse reactions and remained optically clear. Topography showed a smooth
      surface and a profile similar to that of the contralateral nonsurgical eye. The
      implanted matrices promoted regeneration of corneal cells, tear film, and nerves.
      Touch sensitivity was restored, indicating some restoration of function. The
      corneas with implants showed no significant loss of thickness and demonstrated
      stable host-graft integration. CONCLUSIONS: Collagen can be adequately
      stabilized, using water soluble carbodiimides as protein cross-linking reagents,
      in the fabrication of corneal matrix substitutes for implantation. The simple
      cross-linking methodology would allow for easy fabrication of matrices for
      transplantation in centers where there is a shortage of corneas, or where there
      is need for temporary patches to repair perforations in emergency situations.

PMID- 16638994
TI  - Gene expression in rat lacrimal gland duct cells collected using laser capture
      microdissection: evidence for K+ secretion by duct cells.
AB  - PURPOSE: To compare gene expression profiles of lacrimal gland duct and acinar
      cells after laser capture microdissection (LCM) and identify molecular networks
      related to K+ secretion, testing the hypothesis that duct cells are responsible
      for high K+ levels in tears. METHODS: Frozen sections of lacrimal glands from
      five rats were subjected to LCM to isolate pure samples of duct and acinar cells.
      RNA was extracted, amplified, reverse transcribed, and hybridized to rat cDNA
      microarrays. Paired arrays from ducts and acini of the five animals were scanned
      and analyzed with in-house software. Gene expression was confirmed with
      fluorescent antibodies and confocal microscopy. RESULTS: A list of 10,294 genes
      expressed in ducts and acini was searched using gene ontologies related to ion
      transport. From a list of 55 genes that were expressed in ducts, a panel of genes
      hypothesized to be involved in basolateral-to-apical transport of K+ and Cl- was
      chosen for validation by immunofluorescence and confocal microscopy. This
      analysis confirmed translation of the genes of interest and showed that NKCC1,
      Na+,K+-ATPase and the M3 cholinergic receptor are expressed on the basolateral
      membrane of duct cells, whereas KCC1, IK(Ca)1, CFTR, and ClC3 are apically
      localized. CONCLUSIONS: Laser capture microdissection in conjunction with gene
      expression analysis provides an excellent approach for studying lacrimal gland
      duct cells about which relatively little is known at the molecular level. As
      demonstrated in a proposed model, the polarized expression of transporters and
      channels on lacrimal gland duct membranes is consistent with the hypothesis that
      duct cells secrete the relatively high K+ in lacrimal fluid.

PMID- 16638995
TI  - Differential regulation of key stages in early corneal wound healing by TGF-beta
      isoforms and their inhibitors.
AB  - PURPOSE: Inhibition of TGF-beta reduces myofibroblast differentiation and
      fibrosis in the cornea. Determining the actions of distinct TGF-beta isoforms and
      their inhibitors during early corneal wound healing is an essential step in
      guiding therapeutic intervention. METHODS: Bovine serum-free corneal cell and
      wounded organ cultures were challenged with a range of concentrations of TGF
      beta1, -beta2, and -beta3; IL-10; and neutralizing human monoclonal antibodies
      (mAbs) against TGF-beta1 (CAT-192) or -beta2, (CAT-152). Cultures were assessed
      for re-epithelialization, proliferation (cell counts and cresyl violet assay),
      morphology (histologic examination), repopulation of the area under the wound,
      and myofibroblast transformation (alpha-smooth muscle actin) between 0 and 5
      days. RESULTS: TGF-beta1 delayed re-epithelialization, increased repopulation of
      the stroma, increased keratocyte proliferation and was the only isoform to
      promote myofibroblast differentiation. The anti-TGF-beta1 mAb, CAT-192 promoted
      re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-beta3
      had little effect on re-epithelialization but reduced repopulation of the stroma.
      IL-10 promoted corneal re-epithelialization at low doses but inhibited this
      response at high doses. Stromal repopulation was prevented by all doses of IL-10.
      TGF-beta2 or the anti-TGF-beta2 mAb, CAT-152 had little effect on any repair
      parameter. CONCLUSIONS: The results confirm TGF-beta1 as the principal isoform in
      corneal wound healing and suggest that inhibition of the action of TGF-beta1 can
      promote corneal wound healing. Treatment with the anti-TGF-beta1 mAb CAT-192
      accelerates corneal re-epithelialization but reduces cell repopulation of the
      stroma. The cytokines TGF-beta3 and IL-10 have opposing actions to that of TGF
      beta1.

PMID- 16638996
TI  - Strip meniscometry: a new and simple method of tear meniscus evaluation.
AB  - PURPOSE: To investigate the applicability and efficacy of a new and simple method
      of quantification of the volume of tear meniscus, termed "strip meniscometry," in
      the diagnosis of the dry eye syndromes in a prospective controlled study.
      METHODS: One hundred eyes of 50 patients with dry eye (19 males; 31 females) aged
      between 18 and 76 years (mean, 54.3 years), as well as 80 eyes of 40 normal
      subjects aged from 15 to 70 years (mean, 50.8 years; 12 males, 28 females) were
      recruited in this study. The patients and the control subjects underwent strip
      meniscometry for 5 seconds, tear film lipid layer interferometry, tear film break
      up time measurement, and ocular surface vital staining with fluorescein and rose
      bengal dyes and the Schirmer-1 test. RESULTS: Strip meniscometry scores
      correlated with tear quantity and stability, ocular surface staining scores, and
      lipid layer interferometry grades and improved after 2 weeks of punctal plug
      occlusion. CONCLUSIONS: Strip meniscometry is a swift, noninvasive, promising new
      method that is expected to find application in the diagnosis and evaluation of
      the outcome of treatment of dry eye syndromes.

PMID- 16638997
TI  - Increased stress-induced generation of reactive oxygen species and apoptosis in
      human keratoconus fibroblasts.
AB  - PURPOSE: To determine whether keratoconus (KC) corneal fibroblast cultures have
      increased reactive oxygen species (ROS) production and are more susceptible to
      stress-related challenges. METHODS: Normal (n = 9) and KC (n = 10) stromal
      fibroblast cultures were incubated in either neutral- or low-pH conditions, with
      or without hydrogen peroxide. Catalase activities were measured with a
      fluorescent substrate assay. Superoxide and ROS/reactive nitrogen species (RNS)
      productions were determined with an amine-reactive green-dye assay and 2',7'
      dichlorodihydrofluorescein diacetate (H2DCFDA) dye assay, respectively. Cell
      viability was analyzed by a dye-exclusion assay. Caspase 3 activity was measured
      by a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was
      used to measure the mitochondrial membrane potential (delta psi m). RESULTS: KC
      fibroblasts had increased superoxide and ROS/RNS production (6.2-fold, P < 0.001
      and 1.8-fold, P < 0.001, respectively) and catalase activity (P < 0.01) with
      higher concentrations of H2O2 compared with normal cultures (P = 0.16). After a
      low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3
      fold, P < 0.02), showed higher caspase-3 activity (7.5-fold, P < 0.02) and
      decreased delta psi m (2.6-fold, P < 0.04), and had decreased cell viability
      (37%, P < 0.005 vs. 20%, P < 0.27) compared with normal fibroblasts. CONCLUSIONS:
      Under identical conditions, KC fibroblasts had increased basal generation of
      ROS/RNS and were more susceptible to stressful challenges (low-pH and/or H2O2
      conditions) than were normal fibroblasts. In addition, the stressed KC
      fibroblasts possessed characteristics similar to those found in the intact KC
      corneas (increased catalase activity, ROS production, and apoptosis). These
      properties may play a role in the pathogenesis of KC.

PMID- 16638998
TI  - Increased apoptosis and abnormal wound-healing responses in the heterozygous
      Pax6+/- mouse cornea.
AB  - PURPOSE: Corneal wound healing involves a cascade of interactions between the
      epithelium and stroma. Pax6 is upregulated, and early events include epithelial
      cell migration and apoptosis of superficial keratocytes. The mouse heterozygous
      Pax6 (Pax6+/-) corneal phenotype mimics human aniridia-related keratopathy (ARK),
      and some aspects of wound healing have been shown to be abnormal, including
      matrix metalloproteinase (MMP)-9 expression. The purpose of this study was to
      test whether the Pax6+/- genotype affects corneal wound-healing responses,
      including stromal cell apoptosis, epithelial cell migration rate, and MMP
      secretion in culture. METHOD: Pax6+/- and wild-type (Pax6+/+) mice were killed
      and their corneas wounded by epithelial debridement. Whole eyes were cultured in
      organ culture and corneal epithelial healing rates and keratocyte apoptosis were
      quantified by topical fluorescein staining and TUNEL, respectively. Dissociated
      corneal epithelial cells from Pax6+/- and wild-type mice were cultured, and the
      activities of secreted MMP-9 were determined by zymography. RESULTS: Wound
      healing rates during the first 6 hours were significantly faster for larger
      wounds and for Pax6+/- corneas. Compared with wild-type, wounded Pax6+/- eyes
      showed significantly more stromal cell apoptosis, and cultured Pax6+/- corneal
      epithelial cells produced lower MMP-9 activity. CONCLUSIONS: The cumulative
      effect of abnormal wound-healing responses, characterized by increased stromal
      cell apoptosis and reduced levels of MMP-9 secretion may contribute to the
      corneal changes in the Pax6+/- mice. Possible contributions of elevated stromal
      cell apoptosis and other abnormal wound-healing responses to ARK are discussed.

PMID- 16638999
TI  - Preservation and expansion of the primate keratocyte phenotype by downregulating
      TGF-beta signaling in a low-calcium, serum-free medium.
AB  - PURPOSE: To demonstrate whether the original keratocyte phenotype is maintained
      with proliferative activity by suppressing TGF-beta signaling in rhesus monkey
      keratocytes expanded in a serum-free and low-[Ca2+] medium. METHODS: Rhesus
      monkey keratocytes were isolated from central corneal buttons by collagenase
      digestion for 16 hours, seeded on plastic in Dulbecco's modified Eagle's medium
      (DMEM) containing insulin-transferrin-sodium selenite (ITS) supplement (DMEM/ITS)
      or 10% fetal bovine serum (DMEM/10% FBS), or in a defined keratinocyte serum-free
      medium (KSFM). After confluence, cells in KSFM were continuously subcultured at a
      1-to-3 split. Cellular proliferation was analyzed by immunostaining for Ki67 and
      the MTT assay. The cellular phenotype was determined by immunostaining for
      aldehyde dehydrogenase (ALDH), keratocan, and CD34 and by the expression of
      keratocan promoter-driven enhanced cyan fluorescent protein (ECFP). The stability
      of the keratocyte phenotype was examined by switching KSFM to DMEM/ITS and
      DMEM/10% FBS. TGF-beta signaling was monitored by measuring the promoter activity
      of TGF-beta1, -beta2, and -beta RII after transient adenoviral transfection, and
      cytolocalization of Smad2 and Smad4. RESULTS: In KSFM, monkey keratocytes
      proliferated while maintaining the expression of keratocan, CD34, and ALDH
      proteins and keratocan promoter-driven ECFP for at least 15 passages. The nuclear
      accumulation of Smad2 and Smad4 and the promoter activities of TGF-beta1 and 
      beta RII were significantly downregulated in KSFM compared with DMEM/10% FBS. In
      KSFM, an increase of [Ca2+] to 1.8 mM and addition of 10% FBS synergistically
      downregulated the keratocan promoter activity, facilitated Smad2 and Smad4
      nuclear translocation, and upregulated TGF-beta1 and -beta RII promoter
      activities. CONCLUSIONS: The normal monkey keratocyte phenotype can be maintained
      in a low-calcium, serum-free medium by downregulating Smad-mediated TGF-beta
      signaling.

PMID- 16639000
TI  - The role of PDGF receptor inhibitors and PI3-kinase signaling in the pathogenesis
      of corneal neovascularization.
AB  - PURPOSE: Corneal neovascularization remains an unsolved therapeutic problem.
      Platelet-derived growth factor (PDGF) is directly linked to vessel formation and
      stabilization. This study was undertaken to elucidate the mechanisms by which
      PDGF exerts its effects on corneal angiogenesis. METHODS: Corneal
      neovascularization was induced in C57 mice by removal of the limbal epithelium.
      When mature vessels appeared after 7 days, mice were treated with the PDGF
      receptor-beta inhibitor AG 1296 or the phosphatidylinositol 3-kinase (PI3-K)
      inhibitors wortmannin and LY294002, respectively, using an intraperitoneally
      implanted miniosmotic pump. At day 14 after scraping, corneas of treated and
      untreated (control) mice were dissected and immunostained with FITC-CD31 antibody
      for endothelial cells and with Cy3-SMA (smooth muscle actin) for pericytes. VEGF
      (vascular endothelial growth factor), ang1/2 (angiopoietin 1 and 2), and PDGF
      mRNA levels of treated and untreated corneas were determined by real-time RT-PCR.
      RESULTS: Mice treated with the PDGF inhibitor AG 1296 showed an inhibition of
      corneal neovascularization of 21.1% and a reduction of pericytes of 52% in the
      newly formed vessels compared with untreated animals. VEGF, ang1, ang2, and PDGF
      mRNA expression was reduced in the corneas of AG 1296-treated mice compared with
      the respective control. Treatment with the PI3-K inhibitors wortmannin and
      LY29002 had similar effects, inducing a decrease in corneal neovascularization
      and a reduction of VEGF, ang1, ang2, and PDGF mRNA levels. CONCLUSIONS:
      Inhibition of the PDGF signal pathway results in loss of pericytes and a
      reduction in vessel density in the neovascularized cornea that correlates with
      reduced expression of PDGF, ang1/2, and VEGF mRNA. Furthermore, PI3-K was shown
      to be involved in the regulation of VEGF, ang1, and PDGF, as the PI3-K inhibitors
      wortmannin or LY294002 had similar effects. Because PDGF is a known stimulus for
      PI3-K activation, it can be postulated that the observed decrease in VEGF,
      ang1/2, and PDGF mRNA levels on administration of the PDGF inhibitor is caused by
      the decreased activation of the PI3-K signaling cascade.

PMID- 16639001
TI  - Expression and regulation of cornified envelope proteins in human corneal
      epithelium.
AB  - PURPOSE: Stratified squamous epithelial cells assemble a specialized protective
      barrier structure on their periphery, termed the cornified envelope. The purpose
      of this study was to evaluate the presence and distribution of cornified envelope
      precursors in human corneal epithelium, their expression in human corneal
      epithelial cell cultures, and the effect of ultraviolet radiation (UVB) and
      transglutaminase (TG) inhibition on their expression. METHODS: Tissue
      distribution of small proline-rich proteins (SPRRs) and filaggrin and involucrin
      was studied in human cornea sections by immunofluorescence staining. Primary
      human corneal epithelial cells (HCECs) from limbal explants were used in cell
      culture experiments. A single dose of UVB at 20 mJ/cm2 was used to stimulate
      these cells, in the presence or absence of mono-dansyl cadaverine (MDC), a TG
      inhibitor. SPRR2 and involucrin protein levels were studied by immunofluorescence
      staining and Western blot analysis. Gene expression of 12 proteins was
      investigated by semiquantitative reverse transcription-polymerase chain reaction.
      RESULTS: In human cornea tissue, SPRR1, SPRR2, filaggrin, and involucrin protein
      expression were detected in the central and peripheral corneal and limbal
      epithelium. In HCECs, SPRR2 and involucrin proteins were detected in the
      cytosolic fraction, and involucrin levels increased after UVB. Both SPRR2 and
      involucrin levels accumulated in the presence of MDC. Nine genes including
      involucrin, SPRR (types 1A, 1B, 2A, 2B, and 3), late envelope protein (LEP) 1 and
      16, and filaggrin were expressed by HCECs. SPRR 4, loricrin, and LEP 6
      transcripts were not detected. UVB downregulated SPRR (2A, 2B) and LEP 1
      transcripts. CONCLUSIONS: Various envelope precursors are expressed in human
      corneal epithelium and in HCECs, acute UVB stress differentially alters their
      expression in HCECs. The expression of envelope precursors and their rapid
      modulation by UVB supports the role of these proteins in the regulation of ocular
      surface stress. TG function may be relevant in the regulation of soluble
      precursors in UVB-stimulated corneal epithelium.

PMID- 16639002
TI  - Two waves of neutrophil emigration in response to corneal epithelial abrasion:
      distinct adhesion molecule requirements.
AB  - PURPOSE: Corneal abrasion results in an inflammatory response characterized by
      leukocyte emigration into the corneal stroma. Adhesion molecules play a critical
      role in leukocyte emigration to wound sites, but differences are evident in
      different vascular beds. In this study, the contributions of two families of
      adhesion molecules to neutrophil emigration into the cornea were investigated.
      METHODS: Re-epithelialization, patterns of neutrophil influx and CXC chemokine
      production were assessed in C57Bl/6 mice after removal of a 2-mm diameter area of
      central corneal epithelium. Comparisons were made between wild-type (WT) mice and
      mice with targeted deletions of genes for CD18 (CD18(-/-)) or P- and E-selectin
      (P/E-sel(-/-)) or in mice with antibody-induced neutropenia. RESULTS: Wild-type
      mice exhibited neutrophil emigration in two waves, the first peaking at 18 hours
      and the second at 30 hours after wounding, 6 hours after epithelial wound closure
      and peak levels of corneal CXCL1. In CD18(-/-) animals, only a single wave of
      neutrophil influx was seen, and it was temporally and quantitatively equivalent
      to the second wave in WT. In P/E-sel(-/-) mice, neutrophil influx was markedly
      depressed throughout the 48-hour observation period. Re-epithelialization was
      significantly delayed in mice with adhesion molecule deletions and in neutropenic
      animals. Transfer of wild-type leukocytes into CD18(-/-) mice resulted in
      neutrophil emigration into the injured cornea within 18 hours of wounding and
      improved closure of the epithelium. CONCLUSIONS: Neutrophil emigration into
      corneal stroma after epithelial abrasion occurs in two waves. The first is
      dependent on CD18 integrins and selectins, whereas the second is CD18-independent
      but requires selectins. Early leukocyte emigration appears to promote re
      epithelialization.

PMID- 16639004
TI  - Topographic and morphologic analyses of retinal ganglion cell loss in old
      DBA/2NNia mice.
AB  - PURPOSE: To evaluate the relationship between retinal ganglion cell (RGC) size,
      density distribution, and survival in senescent DBA2/NNia mice that develop
      pigmentary glaucoma. To evaluate the validity of nearest neighbor distance (NND),
      a measure of focal density for surviving RGCs in the retina, as a method to
      quantify RGC loss in mice. METHODS: Fifteen-month-old DBA2/NNia mice were labeled
      retrogradely with fluorogold. Retinas were flat mounted and imaged in their
      entirety using an epifluorescence microscope with a motorized stage. Digital maps
      of the retinal wholemounts were constructed to automatically count and establish
      spatial coordinates for RGCs over the entire retina. RGC size and NND were
      determined from these maps. RESULTS: RGC counts in the group of 15-month-old
      DBA/2NNia animals ranged from 22,330 to 92,157 cells per retina. Mean RGC cell
      size per retina ranged from 22.35 to 35.64 microm2 and correlated linearly with
      total RGC counts. NND distribution histograms were compared for retinas with
      variable degrees of RGC loss. The distribution of NNDs in each retina was skewed
      toward larger distance values in more affected retinas. In partially damaged
      retinas, areas with severe pathology coincided with areas of maximal loss of
      large RGCs, and areas of preserved RGCs correlated with larger cell sizes.
      CONCLUSIONS: Damaged retinas have a smaller mean cell size, indicating
      preferential loss of larger RGCs or size reduction of surviving cells. NND
      analysis of the RGC population in a retina is a useful measure of glaucomatous
      RGC loss. The skewed NND distribution of surviving RGCs and the finding that RGC
      loss correlates with a shift/amplitude change in the mode of the histogram and
      its tail suggests two different patterns of RGC loss possibly attributable to
      different pathologic processes in glaucomatous DBA/2 mice.

PMID- 16639003
TI  - Beta1 and beta3 integrins cooperate to induce syndecan-4-containing cross-linked
      actin networks in human trabecular meshwork cells.
AB  - PURPOSE: To characterize the molecular composition of cross-linked actin networks
      (CLANs) and the regulation of their formation by integrins in normal human
      trabecular meshwork (TM) cells. CLANs have been observed in steroid-treated and
      glaucomatous TM cells and have been suggested to contribute to decreased outflow
      facility by altering the contractility of the TM. METHODS: Immunofluorescence
      microscopy was used to identify molecular components of CLANs and quantitate CLAN
      formation in HTM cells plated on coverslips coated with various extracellular
      matrix (ECM) proteins (fibronectin, types I and IV collagen, and vitronectin),
      vascular cell adhesion molecule (VCAM)-1, or activating antibodies against beta1,
      beta3, or alpha2beta1 integrins. These integrin antibodies were also used as
      soluble ligands. RESULTS: CLAN vertices contained the actin-binding proteins
      alpha-actinin and filamin and the signaling molecules syndecan-4 and PIP2. CLANs
      lacked Arp3 and cortactin. CLAN formation was dependent on the ECM substrate and
      was significantly higher on fibronectin and VCAM-1 compared with vitronectin,
      types I or IV collagen. Adsorbed beta1 integrin antibodies also induced CLANs,
      whereas adsorbed beta3 or alpha2beta1 integrin antibodies did not. Soluble beta3
      integrin antibodies, however, induced CLANs and actually enhanced CLAN formation
      in cells spread on fibronectin, VCAM-1, type I or type IV collagen, or beta1
      integrin antibodies. CONCLUSIONS: CLANs are unique actin-branched networks whose
      formation can be regulated by beta1 and beta3 integrin signaling pathways. Thus,
      integrin-mediated signaling events can modulate the organization of the actin
      cytoskeleton in TM cells and hence could participate in regulating cytoskeletal
      events previously demonstrated to be involved in controlling outflow facility.

PMID- 16639005
TI  - Otago glaucoma surgery outcome study: cytology and immunohistochemical staining
      of bleb capsules around Molteno implants.
AB  - PURPOSE: To describe the cytology and immunohistochemistry of Molteno implant
      capsules from cases of primary and secondary glaucoma. METHODS: Histologic
      features of capsules including cell cytology, the distribution of activated
      (proliferating) cells, apoptosing cells, and membrane bound vesicles (presumed
      death messengers) were assessed by light microscopy and correlated with
      clinicopathological features in 10 noninflamed eyes with good intraocular
      pressure control (nine autopsy and one enucleation) obtained from 2 months to
      16.8 years after insertion of Molteno implants. RESULTS: All bleb capsules
      demonstrated two distinct layers. The thin external layer was cellular with
      fairly numerous small blood vessels coursing through normally staining, regularly
      arranged collagen fibers. The thicker, deeper layer was avascular, relatively
      acellular, and characterized by regularly arranged swollen and fragmented
      collagen fibers. Most cells in the external layer appeared normal; however,
      between 5% (in recently formed blebs) and approximately 50% (in well established
      blebs) showed cytological and/or immunohistochemical changes characteristic of
      metabolic activation and/or apoptosis. All cells in the deeper layer, regardless
      of time after surgery, also demonstrated cytological and/or immunohistochemical
      staining characteristic of metabolic activation and/or apoptosis. In addition,
      the deeper layer evidenced large numbers of minute membrane-bound vesicles
      (presumed death messengers). CONCLUSIONS: The balance between activation and
      apoptosis regulates the thickness and permeability of bleb capsules, and the
      normal lifecycle of bleb capsules includes continual inner surface degeneration
      and external surface renewal.

PMID- 16639006
TI  - Clusterin deficiency in eyes with pseudoexfoliation syndrome may be implicated in
      the aggregation and deposition of pseudoexfoliative material.
AB  - PURPOSE: To determine the role of the extracellular chaperone clusterin in the
      pathophysiology of pseudoexfoliation (PEX) syndrome/glaucoma, which is
      characterized by the stable deposition of abnormal extracellular fibrillar
      material in anterior segment tissues. METHODS: Real-time PCR, in situ
      hybridization, and immunohistochemistry were applied to analyze the mRNA and
      protein expression of clusterin in PEX eyes of patients without and with glaucoma
      and to compare them with eyes of patients with primary open-angle glaucoma and
      angle-closure glaucoma and with normal control eyes. Aqueous levels of clusterin
      were determined by Western blot analysis. Real-time PCR and Western blot analysis
      were used to study the effect of TGF-beta1, which is significantly increased in
      the aqueous humor of PEX eyes, on clusterin expression by nonpigmented ciliary
      epithelial cells in vitro. RESULTS: Clusterin mRNA was ubiquitously expressed in
      most ocular cells and tissues, particularly in the epithelium of ciliary
      processes, whereas the protein was mostly located to extracellular structures,
      such as ocular basement membranes and stromal fibers. Real-time PCR and in situ
      hybridization displayed significant downregulation of clusterin mRNA in all
      anterior segment tissues of PEX eyes, irrespective of the presence or type of
      glaucoma, compared with normal and glaucomatous control eyes, whereas posterior
      segment tissues did not show any differential expression. A generally decreased
      immunoreactivity, but a prominent binding of clusterin to all PEX deposits, could
      be observed in ocular tissues of PEX eyes. Clusterin levels in aqueous humor were
      significantly reduced in eyes of patients with PEX syndrome compared with normal
      and glaucomatous control eyes. The expression of clusterin mRNA and protein in
      nonpigmented ciliary epithelial cells was significantly downregulated by TGF
      beta1 in vitro. CONCLUSIONS: Considering the known role of clusterin as a highly
      efficient extracellular chaperone, its deficiency in the anterior segment of PEX
      eyes may promote the stress-induced aggregation and stable deposition of the
      pathologic extracellular matrix product characteristic of PEX syndrome.

PMID- 16639007
TI  - Effects of latrunculin-B on outflow facility and trabecular meshwork structure in
      human eyes.
AB  - PURPOSE: To determine the effect of the F-actin-disrupting agent latrunculin-B on
      aqueous outflow facility and trabecular meshwork architecture in human eyes.
      METHODS: After baseline facility measurement in human eye bank eyes (n = 9
      pairs), one eye of each pair received anterior chamber exchange and continued
      perfusion with medium containing 1 microM latrunculin-B. Contralateral eyes were
      treated in a similar manner with vehicle. Eyes were fixed by anterior chamber
      exchange and perfusion with universal fixative at 8 mm Hg (corresponding to a
      physiologic pressure of 15 mm Hg in vivo), and outflow pathway tissues were
      examined by transmission and scanning electron microscopy. RESULTS: Perfusion of
      eyes with 1 microM latrunculin-B caused a continuous and ongoing increase in
      outflow facility, resulting in a net facility difference of 64% 2 hours after
      drug administration (P < 0.006). Transmission electron microscopy showed subtle
      and focal detachment of the inner wall of Schlemm's canal, rarefaction of the
      juxtacanalicular tissue (JCT), and cell-cell and cell-matrix detachment. Scanning
      electron microscopy showed collapsed vacuoles in the inner wall of Schlemm's
      canal and a marked increase in the number and size of border (paracellular) pores
      in the inner wall. CONCLUSIONS: Latrunculin-B increases outflow facility in
      postmortem human eyes. The mechanism of facility increase is most likely due to
      loss of mechanical integrity of the trabecular meshwork as a consequence of
      reduction in cell-cell and cell-matrix adhesion. The facility increase and the
      extent of inner wall separation from the JCT that we observed were both
      qualitatively similar to that reported in living monkey eyes, but the magnitude
      of the facility increase and morphologic changes were much less than in the
      living monkey. This supports the idea that inner wall separation from the JCT may
      modulate outflow facility.

PMID- 16639008
TI  - Noladin ether acts on trabecular meshwork cannabinoid (CB1) receptors to enhance
      aqueous humor outflow facility.
AB  - PURPOSE: To study the effects of 2-arachidonyl glyceryl ether (noladin ether), an
      endocannabinoid ligand selective for cannabinoid (CB)1 receptor, on aqueous humor
      outflow facility, to investigate the involvement of trabecular meshwork CB1
      receptors and the p42/44 MAP kinase signaling pathway and to explore the cellular
      mechanisms of noladin ether-induced changes of outflow facility. METHODS: The
      effects of noladin ether on aqueous humor outflow facility were measured in a
      porcine anterior-segment-perfused organ culture model. The expression of CB1
      receptors on cultured porcine trabecular meshwork cells and the coupling of these
      receptors to p42/44 MAP kinase was determined by immunofluorescence microscopy
      and Western blot analysis. Both Western blot and zymography were used to monitor
      the effects of noladin ether on matrix metalloproteinase (MMP)-2. In morphologic
      studies, AlexaFluor 488-labeled phalloidin staining was used to examine actin
      filament, and immunohistochemistry with anti-paxillin antibodies was used to
      detect focal adhesions. RESULTS: Within 1 hour after adding 3, 30, or 300 nM of
      noladin ether, the aqueous humor outflow facility increased concentration
      dependently. The effect of 30 nM of noladin ether was completely blocked by
      SR141716A, a selective CB1 antagonist. Positive signals were detected on cultured
      porcine trabecular meshwork cells with an anti-CB1 antibody in immunofluorescence
      microscopy and Western blot studies. Treatment of trabecular meshwork cells with
      30 nM of noladin ether activated p42/44 MAP kinase, whereas pretreatment with
      SR141716A blocked the p42/44 MAP kinase-activating effects of noladin ether. In
      addition, the enhancement of outflow facility induced by noladin ether was
      blocked by pretreatment of porcine anterior segments with PD98059, an inhibitor
      of p42/44 MAP kinase pathway. Furthermore, noladin ether treatment caused
      rounding of trabecular meshwork cells, and there was a decrease of actin stress
      fibers, as well as a decrease in focal adhesions. These noladin ether-induced
      morphologic changes were also blocked by SR141716A and PD98059. CONCLUSIONS: The
      results demonstrate for the first time that administration of noladin ether, an
      endocannabinoid agonist selective for the CB1 receptor, increases aqueous humor
      outflow facility. The data also show that noladin ether-induced enhancement of
      outflow facility is mediated through the trabecular meshwork CB1 receptor, with
      an involvement of p42/44 MAP kinase signaling pathway and changes in actin
      cytoskeletons.

PMID- 16639009
TI  - Diagnostic capability of optical coherence tomography in evaluating the degree of
      glaucomatous retinal nerve fiber damage.
AB  - PURPOSE: To evaluate the role and ability of optical coherence tomography (OCT)
      to detect differences in peripapillary retinal nerve fiber layer (RNFL) thickness
      between normal and glaucomatous eyes and also between different severities of
      glaucoma. METHOD: This cross-sectional observational study included 160 eyes of
      160 healthy subjects and 134 eyes of 134 patients with primary open-angle
      glaucoma (POAG). Peripapillary RNFL thickness was measured on OCT using the fast
      RNFL thickness protocol. The RNFL thickness parameters used for evaluation
      included average RNFL thickness and inferior, superior, nasal, and temporal RNFL
      thickness. The glaucomatous eyes were subdivided into three subgroups on the
      basis of visual field defects and a fourth subgroup of eyes blinded by glaucoma.
      RNFL thickness parameters were compared among the normal eyes and the glaucoma
      subgroups. Correlation of global visual field indices with RNFL thickness
      parameters was also performed. RESULTS: The average RNFL in control subjects,
      early glaucoma, moderate glaucoma, severe glaucoma, and blind glaucoma were
      102.30 +/- 10.34, 77.68 +/- 15.7, 66.07 +/- 15.5, 53.65 +/- 14.2, and 44.93 +/-
      4.95 microm, respectively. There was a significant difference in all RNFL
      thickness parameters between normal and all glaucoma subgroups (P < 0.001).
      Average and inferior RNFL thicknesses showed the highest area under the receiver
      operating characteristic curve, with 0.905 and 0.862 for normal versus early
      glaucoma, 0.705 and 0.722 for early versus moderate glaucoma, 0.737 and 0.717 for
      moderate versus severe glaucoma, and 0.635 and 0.584 for severe versus blind
      glaucoma. Both mean deviation (MD) and corrected pattern standard deviation
      (CPSD) showed a significant correlation with all the RNFL thickness parameters in
      eyes with glaucoma (P < 0.001). CONCLUSIONS: RNFL thickness measured on OCT may
      serve as useful adjuncts in accurately and more objectively distinguishing normal
      from glaucomatous eyes, even in the early stages of glaucoma and may help to
      differentiate various severities of glaucoma. Average and inferior RNFL
      thicknesses are among the most efficient parameters for distinguishing such a
      differentiation. RNFL thicknesses in eyes blinded by glaucoma provide an estimate
      of the component of the RNFL thickness, which is not related to visual function.

PMID- 16639010
TI  - Ultrastructural and biochemical evaluation of the porcine anterior chamber
      perfusion model.
AB  - PURPOSE: To evaluate a porcine anterior chamber perfusion model and to test the
      transferability of data obtained with this model to the human system. METHODS:
      Porcine eyes were obtained from a local abattoir and processed within 2 hours
      after death. Anterior chambers of 42 pairs of eyes were dissected with removal of
      lens, vitreous, iris, and ciliary processes and perfused for 72 (40 pairs) or 140
      (2 pairs) hours with medium or medium supplemented with 10 ng/mL transforming
      growth factor (TGF)-beta2. Facility was continuously measured. Afterward,
      trabecular meshwork (TM) specimens from all quadrants were prepared, and sections
      were analyzed morphologically and with immunohistochemical methods. TM sections
      of 10 nonperfused pairs of eyes were used as the control. RNA and protein was
      extracted from the TM specimens. Expression of alphaB-crystallin, fibronectin
      (FN), plasminogen activator inhibitor (PAI)-1, thrombospondin (TSP)-1, and
      connective tissue growth factor (CTGF) mRNA and protein in medium-perfused and
      TGF-beta2-perfused anterior segments was examined by Northern and Western blot
      analyses. RESULTS: The nonperfused TM showed prominent differences between the
      temporal and nasal quadrants. Temporally, the ciliary muscle (CM) was pronounced,
      the scleral sulcus was long and flat, and the scleral spur extended toward the
      iris root. Nasally, the CM was thin, the sulcus deep, and the spur compact. The
      outer TM was expanded between the scleral spur and cornea throughout the entire
      circumference. On the ultrastructural level, the elastic network was connected to
      the cribriform TM cells and the aqueous plexus endothelium. Perfusion itself had
      only small effects on the morphology of the outer TM. Aqueous plexus loops
      remained open, and TM cells showed no signs of necrosis or pyknosis. alphaB
      crystallin expression was significantly increased in perfused eyes. Perfusion
      with TGF-beta2 for 72 hours reduced outflow facility to approximately 60% of that
      of the medium-perfused control. TM cells adjacent to putative drainage pathways
      showed enlarged cisterns of rough endoplasmic reticulum (rER), a sign of active
      protein synthesis. Expression of alphaB-crystallin and FN mRNA were elevated by
      factors of 5 and 3, respectively. The proteins were upregulated by a factor of
      2.5. In addition, TGF-beta2 upregulated PAI-1 (1.7-fold) and TSP-1 (1.6-fold)
      proteins, two factors shown to be TGF-beta2 responsive in human TM cell culture
      experiments. CTGF expression was not altered. CONCLUSIONS: These new
      ultrastructural investigations indicate that the cribriform and subendothelial
      regions of the porcine TM have an architecture similar to that of the primate TM.
      The biochemical and physiological response to TGF-beta2 was identical with that
      described in human TM cell culture and anterior chamber perfusion. The porcine
      anterior chamber perfusion model is valid for the human system.

PMID- 16639011
TI  - N-chlorotaurine is an effective antiviral agent against adenovirus in vitro and
      in the Ad5/NZW rabbit ocular model.
AB  - PURPOSE: To determine whether N-chlorotaurine (NCT) demonstrates antiviral
      activity against adenovirus (Ad) in vitro and in the Ad5/NZW rabbit ocular model.
      METHODS: The in vitro activity of NCT was evaluated by incubating different Ad
      serotypes with several concentrations of NCT for 1 hour and determining the
      reduction in Ad titers. In rabbit study 1, Ad5-infected eyes were treated with
      2.5%, 2.0%, and 1.0% NCT; 0.5% cidofovir; or saline. NCT and saline groups were
      treated 10 times for 1 day and then 5 times daily for 6 days. In rabbit study 2,
      Ad5-infected eyes were treated with 1.0% NCT/0.1% ammonium chloride (NH4Cl), 0.1%
      NCT/1.0% NH4Cl, 0.1% NCT/0.1% NH4Cl, and 0.5% cidofovir or saline. The NCT and
      saline groups were treated five times daily for 10 days. Cidofovir-treated eyes
      received the authors' standard cidofovir dose regimen: twice daily for 7 days.
      RESULTS: In vitro, NCT demonstrated concentration-dependent direct inactivation
      of all ocular Ad serotypes tested. Rabbit study 1: 2.5%, 2.0%, 1.0% NCT, and
      cidofovir demonstrated significantly fewer positive cultures per total cultures
      during days 1 to 14, compared with saline. Rabbit study 2: 1.0% NCT/0.1% NH4Cl,
      0.1% NCT/1.0% NH4Cl, 0.1% NCT/0.1% NH4Cl, and cidofovir demonstrated
      significantly fewer positive cultures per total cultures, during days 1 to 14;
      shorter durations of shedding; and lower mean combined titers, during days 7 to
      14, compared with saline. Cidofovir was significantly more effective than NCT in
      several outcome measures in both rabbit studies. CONCLUSIONS: NCT demonstrated
      antiviral activity against adenovirus in vitro and in vivo. Further development
      of NCT as a topical antimicrobial is indicated.

PMID- 16639012
TI  - Mapping immune responses to mRBP-3 1-16 peptide with altered peptide ligands.
AB  - PURPOSE: Experimental autoimmune uveoretinitis (EAU) can be induced in C57BL/6
      mice (I-A(b)) using human retinoid-binding protein-3 (hRBP-3, previously IRBP)
      residues 1-20. This study of a truncated murine peptide (mRBP-3 1-16) was
      conducted to determine its pathogenic potential and to characterize partially its
      interaction with specific T cells. METHODS: After immunization with mRBP-3 1-16
      or hRBP-3 1-20, EAU was assessed by immunohistochemistry. The immune response was
      assessed by tritiated thymidine incorporation and cytokine production analyzed by
      enzyme-linked immunosorbent assay (ELISA). T-cell receptor (TCR)- and major
      histocompatibility complex (MHC)-binding of mRBP-3 1-16 was studied by modeling
      and by using altered peptide ligands (APLs) and T-cell clones. RESULTS: mRBP-3 1
      16 induced EAU in C57BL/6 mice, with severity and kinetics comparable to that
      after immunization with hRBP-3 1-20. T cells taken from mice immunized with mRBP
      3 1-16 had a Th1 phenotype and proliferated in response to reactivation with mRBP
      3 1-16, hRBP-3 1-20, or mRBP-3 1-16 APLs. mRBP-3 1-16 APLs elicited at least five
      distinct patterns of reactivity when tested with the mRBP-3 1-16-reactive T-cell
      clones. CONCLUSIONS: mRBP-3 1-16 immunizes and causes EAU in C57BL/6 mice. The
      studies using T-cell clones and APLs demonstrate that the immune response to mRBP
      3 1-16 is drawn from a diverse population of antigen-specific T cells with a Th1
      phenotype. Modeling and analysis of clones indicate that nonpathogenic T cells of
      an mRBP-3 1-16-reactive T-cell line recognize the peptide in a single register.

PMID- 16639013
TI  - A transgenic mouse model for human autosomal dominant cataract.
AB  - PURPOSE: To characterize lenses from transgenic mice designed to express mutant
      and wild-type alphaA-crystallin subunits. METHODS: A series of transgenic mouse
      strains was created to express mutant (R116C) and wild-type human alphaA
      crystallin in fiber cells of the lens. Dissected lenses were phenotypically
      scored for the presence and extent of opacities, fiber cell morphology, and
      posterior suture morphology. Gene transcripts derived from integrated transgenes
      were detected by reverse transcriptase-PCR. Distribution of expressed transgenic
      protein was determined by immunohistochemical staining of lens tissue sections.
      The abundance of endogenous and transgenic lens proteins was estimated by
      quantitative Western blot analysis. RESULTS: Expression of R116C mutant alphaA
      crystallin subunits resulted in posterior cortical cataracts and abnormalities
      associated with the posterior suture. The severity of lens abnormalities did not
      increase between the ages of 9 and 30 weeks. With respect to opacities and
      morphologic abnormalities, lenses from transgenic mice that express wild-type
      human alphaA-crystallin subunits were indistinguishable from age-matched
      nontransgenic control mice. Similar phenotypes were observed in different
      independent lines of R116C transgenic mice that differed by at least two orders
      of magnitude in the expression level of the mutant transgenic protein.
      CONCLUSIONS: The results show that lens opacities and posterior sutural defects
      occur when mutant R116C alphaA-crystallin subunits are expressed on the
      background of wild-type endogenous mouse alpha-crystallins. Low levels of R116C
      alphaA-crystallin subunits are sufficient to induce lens opacities and sutural
      defects.

PMID- 16639014
TI  - Role of the proteasome in TGF-beta signaling in lens epithelial cells.
AB  - PURPOSE: The durability of the ubiquitin proteasome pathway in the mammalian lens
      makes this enzyme system a potential contributor to certain cataracts and
      posterior capsular opacification (PCO). The present study addresses proteasome
      involvement in TGF-beta induced, cataract-associated gene activation in human
      lens cells. METHODS: HLE B-3 cells were treated with TGF-beta, in combination
      with the proteasome inhibitors MG-132 or lactacystin. TGF-beta target gene
      expression was measured by semiquantitative RT-PCR. Annexin-FITC staining and
      flow cytometry were used to assess apoptosis levels. Western blot analyses were
      performed with anti-SnoN and anti-Smad2 antibodies. RESULTS: TGF-beta induced the
      expression of alpha-smooth muscle actin, fibronectin, and TGF-beta-inducible gene
      mRNA in HLE B-3 cells and primary cultured human lens cells from donor tissues.
      TGF-beta also induced a time-dependent decrease in the level of the Smad
      repressor SnoN. Gamma-glutamyl-cysteine synthetase (gamma-GCS) mRNA levels
      decreased in the presence of TGF-beta. Proteasome inhibitor cotreatment blocked
      the induction of alpha-SMA mRNA, the loss of SnoN protein, the decrease in gamma
      GCS mRNA, and TGF-beta-induced apoptosis. CONCLUSIONS: The HLE B-3 cell line and
      primary cultured human lens cells respond similarly to TGF-beta treatments by
      activating cataract-related gene expression. This response in both of these model
      systems is blocked by inhibiting the proteasome. This suggests that the
      proteasome can mediate cataract and PCO-associated changes and therefore is a
      novel target of medical therapy.

PMID- 16639015
TI  - Human lens capsule thickness as a function of age and location along the sagittal
      lens perimeter.
AB  - PURPOSE: To investigate the variation in the thickness of the human lens capsule
      along the lens perimeter, as well as its changes with age. METHODS: Altogether,
      26 human donor lenses, aged 12 to 103 years, were histologically processed.
      Sagittal sections were stained for collagen with periodic acid-Schiff (PAS).
      Serial images of the lens border were taken with a photomicroscope and 25x
      objective. Capsular thickness was measured every 250 microm along the entire lens
      perimeter. RESULTS: All studied capsules were thicker anteriorly, continuously
      increasing with age from 11 to 15 microm in average at the anterior lens pole.
      Maximum thickness was located at the anterior midperiphery, increasing with age
      from 13.5 to 16 microm. In most cases, there was a local thinning at a pre
      equatorial zone, recovering to approximately 7 microm at the equator. The latter
      value, as well as the minimal thickness at the posterior pole (mean 3.5 microm),
      did not change with age, whereas the average thickness at the posterior periphery
      decreased from 9 to 4 microm. CONCLUSIONS: The human lens capsule thickness is at
      its maximum at the anterior midperiphery, which appears to be located central to
      the zonular insertion. It increases with age, especially at the anterior pole,
      while the midperipheral zone stabilizes or slightly decreases after the seventh
      decade. The anterior zonular insertion is actually related to a local pre
      equatorial thinning, which remains unchanged with age. There was no posterior
      peripheral thickening, except in a few younger patients, with a modest relative
      maximum roughly at the equator. From here, the posterior capsule becomes
      progressively thinner and also diminishes with age, except for the thinnest, but
      stable posterior pole.

PMID- 16639016
TI  - Correlation between adult diabetic cataracts and red blood cell aldose reductase
      levels.
AB  - PURPOSE: To investigate the correlation between adult diabetic cataracts and
      levels of aldose reductase (AR) in red blood cells (RBCs). METHODS: The study
      involved 337 eyes of 337 patients with diabetes. The extent and severity of lens
      opacity was assessed according to the Lens Opacities Classification System III
      (LOCS III). The AR levels within RBCs were determined with an ELISA. The
      relationship between the AR level in RBCs and the prevalence of nuclear cataract,
      cortical cataract, and posterior subcapsular cataract in patients with diabetes
      was examined. RESULTS: There were no significant alterations in AR level in RBCs
      in patients with a diabetes duration of < or = 10 years and patients < 60 years
      of age. In each subgroup, a higher amount of AR levels in RBCs significantly
      correlated with the prevalence of posterior subcapsular cataracts. A significant
      association between cortical cataract and AR level in RBCs was also seen in a
      subgroup of patients younger than 60 years. CONCLUSIONS: AR emerges as an
      important factor affecting the onset of posterior subcapsular cataracts at the
      early stages of diabetes mellitus. This raises the possibility that AR inhibitors
      could play a useful role in treatment of adult diabetic cataract through its
      inhibition of AR activities.

PMID- 16639017
TI  - Effect of cAMP on porcine ciliary transepithelial short-circuit current, sodium
      transport, and chloride transport.
AB  - PURPOSE: To investigate the effects of 8-bromo-cAMP (cAMP) on porcine ciliary
      transepithelial short-circuit current (Isc) and transport of chloride (Cl-) and
      sodium (Na+). METHODS: With Ussing-type chambers, cAMP-induced changes in Isc,
      electrical resistance (ER), and transepithelial 36Cl- and 22Na+ fluxes were
      measured. Drugs were applied to the nonpigmented epithelium (NPE) and/or
      pigmented epithelium (PE) side(s). The effect of IBMX (1, 5, or 10 microM; 3
      isobutyl-1-methylxanthine) on Isc-increase induced by 8-bromo-cAMP on the PE side
      was also tested. RESULTS: On the NPE side, a single concentration (10 microM, 100
      microM, or 1 mM) of 8-bromo-cAMP induced a biphasic (transient peak followed by
      sustained plateau) Isc increase. On the PE side, 8-bromo-cAMP induced a similar
      but delayed biphasic Isc increase at 1 mM, a slight plateau-Isc increase at 100
      microM, and no Isc increase at 10 microM. In the concentration-response curve,
      the cAMP-induced peak-Isc increase became significant at a concentration 10,000
      times lower on the NPE than on the PE side. At 10 microM, the cumulative cAMP
      induced Isc-increase reached its maximum on the NPE side, but was virtually
      nonexistent on the PE side. IBMX (a phosphodiesterase inhibitor) but not 8-CPT-6
      Phe-cAMP (higher permeability than 8-bromo-cAMP) significantly increased the peak
      Isc concentration-response curve induced by 8-bromo-cAMP (10 nM-1 mM) on the PE
      side. On the NPE but not the PE side, 10 microM 8-bromo-cAMP induced a
      significant but transient increase in net PE-to-NPE 36Cl- flux (1.03 +/- 0.18
      microEq/min per square centimeter; P < 0.001). Neither ER nor transepithelial
      22Na+ flux was changed after cAMP exposure. CONCLUSIONS: In porcine ciliary
      processes, apparently on the NPE side, cAMP triggers a biphasic (transient peak
      followed by a sustained plateau) Isc increase. Only the peak-Isc increase
      involves an increase in net PE-to-NPE Cl- transport.

PMID- 16639018
TI  - Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel
      enzyme for pharmacologic vitreolysis.
AB  - PURPOSE: To investigate the effects of intravitreal injection of nattokinase
      (subtilisin NAT), a serine protease that is produced by Bacillus subtilis
      (natto), for induction of posterior vitreous detachment (PVD). METHODS: Different
      doses of nattokinase (1, 0.1, or 0.01 fibrin-degradation units [FU]) or
      physiologic saline as a control were injected into the vitreous cavity of rabbit
      eyes. Scanning electron microscopy was used to observe the retinal surfaces of
      four rabbit eyes per concentration. Histologic alterations were assessed by light
      microscopy, using four eyes from each group. Electroretinography (ERG) was
      performed to observe retinal function, ranging from 1 hour to 1 week after the
      nattokinase (1 or 0.1 FU) or saline solution administration, using four eyes from
      each group at each time point. Also, findings in all rabbits were monitored by
      slit lamp examination and by indirect ophthalmoscopy with a 20-D lens. RESULTS:
      Scanning electron microscopy showed smooth retinal surfaces, indicating the
      occurrence of PVD at 30 minutes after intervention in all the experimental eyes
      injected with 0.1 or 1.0 FU nattokinase, but none of the control eyes. Light
      microscopy and ERG analysis showed no critical change even after the use of 0.1
      FU nattokinase, an amount sufficient to induce PVD. However, toxicity in the
      forms of preretinal hemorrhage and ERG changes was noted with the higher dose (1
      FU) of nattokinase. CONCLUSIONS: The results suggested that nattokinase is a
      useful enzyme for pharmacologic vitreolysis because of its efficacy in inducing
      PVD.

PMID- 16639019
TI  - In vivo imaging of the photoreceptor mosaic in retinal dystrophies and
      correlations with visual function.
AB  - PURPOSE: To relate in vivo microscopic retinal changes to visual function in
      patients who have various forms of retinal dystrophy. METHODS: The UC Davis
      Adaptive Optics (AO) fundus camera was used to acquire in vivo retinal images at
      the cellular level. Visual function tests consisting of visual fields, multifocal
      electroretinography (mfERG), and contrast sensitivity were measured in all
      subjects by using stimuli that were coincident with areas imaged. Five patients
      with different forms of retinal dystrophy and three control subjects were
      recruited. Cone densities were quantified for all retinal images. RESULTS: In all
      images of diseased retinas, there were extensive areas of dark space between
      groups of photoreceptors, where no cone photoreceptors were evident. These
      irregular features were not seen in healthy retinas, but were apparent in
      patients with retinal dystrophy. There were significant correlations between
      functional vision losses and the extent to which these irregularities, quantified
      by cone density, occurred in retinal images. CONCLUSIONS: AO fundus imaging is a
      reliable technique for assessing and quantifying the changes in the photoreceptor
      layer as disease progresses. Furthermore, this technique can be useful in cases
      where visual function tests provide borderline or ambiguous results, as it allows
      visualization of individual photoreceptors.

PMID- 16639020
TI  - The safety of intraocular ketorolac in rabbits.
AB  - PURPOSE: To assess the safety of a possible substitute treatment for intraocular
      steroid injections, intraocular injections of ketorolac tromethamine, one of the
      nonsteroidal anti-inflammatory drugs, were performed in rabbits. METHODS: Either
      0.5% or 0.25% preservative-free ketorolac tromethamine ophthalmic solution (0.1
      mL) was injected into the vitreous of the right eye of 15 rabbits. Physiologic
      saline solution (BSS; Alcon, Ft. Worth, TX) was injected into the left eye of
      each rabbit as a control. A standard electroretinogram and intraocular pressure
      measurements were obtained before injection, and repeated 1 day and 1, 2, 3, and
      4 weeks after injection. After 4 weeks, the rabbits were euthanatized and the
      retinas examined by light and electron microscopy. Differences in the
      electroretinograms, intraocular pressure, and histopathology between the two eyes
      were recorded. Further, the elimination half-life of the drug in the vitreous was
      assessed. RESULTS: There were no statistically significant differences in
      electroretinograms, or intraocular pressure measurements obtained between the
      ketorolac-injected eyes and the control eyes. The half life of the drug was
      measured to be 2.3 hours. No histopathologic changes were observed in study eyes
      compared with control eyes. CONCLUSIONS: Preservative-free ketorolac tromethamine
      is nontoxic to the retinas of rabbits when injected intravitreally and could be
      considered as an alternative to intraocular steroid injections.

PMID- 16639021
TI  - Retinal toxicity of indocyanine green in albino rabbits.
AB  - PURPOSE: Intravitreal indocyanine green (ICG) is commonly used in vitreoretinal
      surgery. The purpose of this study was to evaluate possible toxicity of ICG in
      the retina of albino rabbits. METHODS: Twenty-two albino rabbits were injected
      intravitreally with 0.1 mL ICG solution in one eye, and three rabbits were
      studied for the effects of 0.1 mL distilled water. All rabbits were injected
      intravitreally with 0.1 mL saline into the fellow eye, which served as the
      control. The electroretinogram (ERG) and visual evoked potential (VEP) were
      recorded from each rabbit at different time intervals after injection. The
      rabbits were killed at the termination of the follow-up periods and their retinas
      prepared for histologic examination at the light microscopic level. RESULTS:
      Three hours after injection, the ERG responses were reduced in amplitude in all
      ICG-injected eyes, and the VEPs were of abnormal pattern (reduced amplitude and
      delayed). Partial dose-dependent recovery was observed during 4 weeks of follow
      up. Light microscopy of the retinas of the experimental eyes exhibited
      considerable damage to all retinal layers in all eyes studied that received the
      highest ICG dose. CONCLUSIONS: ICG is potentially toxic to all retinal layers of
      the albino rabbit. Although it is difficult to extrapolate these findings
      directly to human eyes, caution should be exercised when using ICG
      intravitreally.

PMID- 16639022
TI  - Bone marrow-derived cells home to and regenerate retinal pigment epithelium after
      injury.
AB  - PURPOSE: To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs)
      can home to and regenerate the retinal pigment epithelium (RPE) after induced
      injury. METHODS: Enriched HSCs/HPCs from green fluorescent protein (gfp)
      transgenic mice were transplanted into irradiated recipient mice to track bone
      marrow-derived cells. Physical damage was induced by breaching Bruch's membrane
      and inducing vascular endothelial growth factor A (VEGFa) expression to promote
      neovascularization. RPE damage was also induced by sodium iodate injection (40
      mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression,
      the presence of the Y chromosome, and the presence of melanosomes were used to
      determine whether the injured RPE was being repaired by the donor bone marrow.
      RESULTS: Injury to the RPE recruits HSC/HPC-derived cells to incorporate into the
      RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs
      adopt RPE morphology, express melanosomes, and integrate into the RPE without
      cell fusion. CONCLUSIONS: HSCs/HPCs can migrate to the RPE layer after physical
      or chemical injury and regenerate a portion of the damaged cell layer.

PMID- 16639023
TI  - Mitochondrial potassium ATP channels and retinal ischemic preconditioning.
AB  - PURPOSE: To examine the mechanisms of ischemic preconditioning (IPC) related to
      the opening of mitochondrial KATP (mKATP) channels in the retina. METHODS: Rats
      were subjected to retinal ischemia after IPC, or retinas were rendered ischemic
      after pharmacological opening of mKATP channels. The effects of blocking mKATP
      channel opening, nitric oxide synthase (NOS) subtypes, or protein kinase C (PKC)
      on the protective effect of IPC or on the opening of mKATP channels were studied.
      Electroretinography assessed functional recovery after ischemia.
      Immunohistochemistry and image analysis were used to measure changes in levels of
      reactive oxygen species (ROS) and NOS subtypes and to determine their cellular
      localization. RESULTS: IPC was effectively mimicked by injection of the mKATP
      channel opener diazoxide. Both IPC and its mimicking by diazoxide were completely
      attenuated by the mKATP channel blocker 5-hydroxydecanoic acid (5-HD).
      Nonspecific blockade of NOS by N(omega)-nitro-L-arginine (L-NNA), but not by
      specific inducible (i)NOS or neuronal (n)NOS inhibitors, blunted IPC and IPC
      mimicking, as did blockade of PKC. IPC and diazoxide IPC-mimicking significantly
      enhanced mitochondrial ROS production in the inner retina, an effect blocked by 5
      HD. Mitochondrial ROS colocalized with e- and nNOS in retinal cells after
      stimulation with diazoxide. CONCLUSIONS: The results showed that IPC in the
      retina requires opening of the mKATP channel, and that IPC could be effectively
      mimicked using the mKATP channel opener diazoxide. eNOS-generated nitric oxide,
      PKC, and ROS are activated by opening of the mKATP channel.

PMID- 16639024
TI  - T2-TrpRS inhibits preretinal neovascularization and enhances physiological
      vascular regrowth in OIR as assessed by a new method of quantification.
AB  - PURPOSE: A carboxyl-terminal fragment of tryptophan tRNA synthetase (T2-TrpRS)
      has demonstrated potent angiostatic activity during retinal developmental
      neovascularization in vivo. The effects of T2-TrpRS on pathologic
      neovascularization were tested and compared with a potent VEGF antagonist using
      the mouse model of oxygen-induced retinopathy (OIR). METHODS: C57BL/6J mice were
      transiently exposed to hyperoxic conditions (75% O2) between postnatal day 7 (P7)
      and P12 and then returned to room air. Retinas were isolated, blood vessels
      stained with isolectin Griffonia simplicifolia, images of retinal whole-mounts
      acquired, and the area of vascular obliteration and extent of preretinal
      neovascularization quantified. This method was compared to the commonly used
      method of OIR quantification in which the number of pre-inner limiting membrane
      (ILM) nuclei is counted in serial sections of whole eyes. To assess the
      angiostatic activity of T2-TrpRS, mice were injected intravitreally at P12 with
      either T2-TrpRS, a VEGF aptamer, or vehicle (PBS) alone, and the effects on area
      of obliteration and on preretinal neovascular tuft formation were assessed.
      RESULTS: Using a modified method of quantification in the mouse OIR model based
      on images of isolectin-stained retinal wholemounts, we were able to assess
      reliably and consistently both vascular obliteration and preretinal neovascular
      tuft formation in the same specimen. T2-TrpRS demonstrated potent angiostatic
      activity, reducing the appearance of pathologic neovascular tufts by up to 90%.
      Surprisingly, T2-TrpRS also enhanced physiological revascularization of the
      obliterated retinal vasculature, reducing these areas by up to 60% compared with
      PBS-injected eyes. In contrast, the VEGF antagonist, while similarly reducing
      preretinal neovascular tuft formation, did not enhance revascularization of the
      obliterated areas. CONCLUSIONS: Use of a rapid, quantifiable method to assess the
      effect of T2-TrpRS on retinal angiogenesis in the OIR model demonstrates the
      importance of a quantification system that permits simultaneous analysis of a
      drug's effect on vascular obliteration as well as on preretinal
      neovascularization. The results obtained using this method suggest enhanced
      clinical value for compounds such as T2-TrpRS that not only inhibit pathologic
      neovascularization, but also facilitate physiological revascularization of
      ischemic tissue.

PMID- 16639025
TI  - The iron carrier transferrin is upregulated in retinas from patients with age
      related macular degeneration.
AB  - PURPOSE: Iron can cause oxidative stress, and elevated iron levels have been
      associated with several neurodegenerative diseases including age-related macular
      degeneration (AMD). Transferrin, an iron transport protein, is expressed at high
      levels in the retina. The purpose of this study was to assess transferrin
      involvement in AMD by determining the expression profile of transferrin in
      retinas with AMD compared with retinas without evidence of disease. METHODS:
      Postmortem retinas were obtained from AMD and non-AMD eyes. Expression of
      transferrin was assessed in a microarray dataset from 33 retinas of unaffected
      donors and 12 retinas of patients with AMD (six with neovascular AMD and six with
      non-neovascular AMD). Quantitative real-time RT-PCR (QPCR) was used to confirm
      the microarray results. Transferrin protein expression was assessed by
      semiquantitative Western blot analysis and immunohistochemistry. RESULTS: In
      comparison to unaffected retinas, mean transferrin mRNA levels, as measured by
      microarray analysis were elevated 3.5- and 2.1-fold in non-neovascular and
      neovascular AMD retinas, respectively. Semiquantitative Western blot analysis
      demonstrated a 2.1-fold increase in transferrin protein in AMD eyes.
      Immunohistochemistry showed more intense and widespread transferrin label in AMD
      maculas, particularly in large drusen, Muller cells, and photoreceptors.
      CONCLUSIONS: These data demonstrate that transferrin expression is increased in
      the retinas of patients with AMD relative to those of healthy control patients of
      comparable age. Along with previous studies that have demonstrated elevated iron
      levels in AMD retinas, early onset drusen formation in a patient with retinal
      iron overload resulting from aceruloplasminemia, and retinal degeneration with
      some features of macular degeneration in the iron-overloaded retinas of
      ceruloplasmin/hephestin knockout mice, the present study suggests that altered
      iron homeostasis is associated with AMD.

PMID- 16639026
TI  - Endothelial nitric oxide synthase is expressed in amacrine cells of developing
      human retinas.
AB  - PURPOSE: To examine the expression and cellular distribution pattern of
      endothelial nitric oxide synthase (eNOS) in the developing human retina and to
      compare its expression with that in rats. METHODS: Expression of eNOS was
      examined by immunohistochemistry in retinas of humans ranging from 8.5 to 28
      weeks of gestation (WG) and of rats. RESULTS: In the developing human retina,
      eNOS expression was first detected in the proximal margin of the neuroblastic
      layer in the incipient fovea-surrounding area at 12 WG. At 17 to 28 WG, eNOS
      immunoreactive cells were located in the innermost part of the inner nuclear
      layer and in the ganglion cell layer, expanding to both temporal and nasal
      retinas and the processes projecting into the inner plexiform layer. These eNOS
      positive cells coexpressed syntaxin and glutamate decarboxylase, and are probably
      GABAergic amacrine cells. The onset of eNOS expression in developing amacrine
      cells, however, preceded the invasion of retinal vasculature, long before
      vascular function involving these cells can be expected, suggesting that eNOS has
      a role not only in vasoregulation but also in retinal development. From 20 WG on,
      eNOS was also detected in the photoreceptors adjacent to the fovea. eNOS
      expression in amacrine cells and photoreceptors was observed in the central-to
      peripheral and temporal-to-nasal gradients. However, in the developing rat
      retina, eNOS was expressed exclusively in the vascular endothelial cells.
      CONCLUSIONS: The results support that eNOS plays a role, not only in the
      regulation of vascular function but also in the process of retinal development in
      humans.

PMID- 16639028
TI  - Glial cell reactivity in a porcine model of retinal detachment.
AB  - PURPOSE: Detachment of the neural retina from the pigment epithelium causes, in
      addition to photoreceptor deconstruction and neuronal cell remodeling, an
      activation of glial cells. It has been suggested that gliosis contributes to the
      impaired recovery of vision after reattachment surgery that may involve both
      formerly detached and nondetached retinal areas. Muller and microglial cell
      reactivity was monitored in a porcine model of rhegmatogenous retinal detachment,
      to determine whether gliosis is present in detached and nondetached retinal
      areas. METHODS: Local detachment was created in the eyes of adult pigs by
      subretinal application of hyaluronate. Retinal slices were immunostained against
      glial intermediate filaments and K+ and water channel proteins (aquaporin-4,
      Kir4.1, Kir2.1), and P2Y receptor proteins. In retinal wholemounts, adenosine 5'
      triphosphate (ATP)-induced intracellular Ca2+ responses of Muller cells were
      recorded, and microglial and immune cells were labeled with Griffonia
      simplicifolia agglutinin isolectin I-B4. K+ currents were recorded from isolated
      Muller cells. RESULTS: At 3 and 7 days after surgery, Muller cells in detached
      retinas showed a pronounced gliosis, as revealed by the increased expression of
      the intermediate filaments glial fibrillary acidic protein and vimentin, by the
      decrease of Kir4.1 immunoreactivity and of the whole-cell K+ currents, and by the
      increased incidence of cells that showed Ca2+ responses on stimulation of
      purinergic (P)2 receptors by ATP. By contrast, the immunohistochemical expression
      of Kir2.1 and aquaporin-4 were not altered after detachment. The increase in the
      expression of intermediate filaments, the decrease of the whole-cell K+ currents
      and of the Kir4.1 immunolabeling, and the increase in the Ca2+ responsiveness of
      Muller cells were also observed in attached retinal areas surrounding the focal
      detachment. The density of microglial-immune cells at the inner surface of the
      retinas increased in both detached and nondetached retinal areas. The
      immunoreactivities for P2Y1 and P2Y2 receptor proteins apparently increased only
      in detached areas. CONCLUSIONS: Reactive responses of Muller and microglial cells
      are not restricted to detached retinal areas but are also observed in nondetached
      regions of the porcine retina. The gliosis in the nondetached retina may reflect,
      or may contribute to, neuronal degeneration that may explain the impaired
      recovery of vision observed in human subjects after retinal reattachment surgery.

PMID- 16639027
TI  - Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of
      transgenic and knockout animals.
AB  - PURPOSE: Peripherin/rds and rom-1 have structural roles in morphogenesis and
      stabilization of the outer segment, but little is known about their transport and
      sorting to the rod outer segment. Peripherin/rds and rom-1 trafficking were
      studied in several knockout and transgenic animal models. METHODS: Rod outer
      segment formation and distribution of peripherin/rds and rom-1 were examined by
      immunohistochemistry, electron microscopy, and molecular biological methods in
      wild-type, rhodopsin-knockout, and peripherin/rds-knockout mice. C-terminally
      truncated peripherin/rds (Xper38)-GFP chimeric protein sorting was followed by
      immunofluorescence microscopy in transgenic Xenopus. RESULTS: In developing wild
      type photoreceptors, peripherin/rds was detected exclusively in the distal tip of
      the connecting cilium in advance of outer segment formation. Rhodopsin-knockout
      mice failed to create normal rod outer segments and instead, elaborated
      membranous protrusions at the distal cilium tip. Peripherin/rds and rom-1
      localized to this ciliary membrane in rhodopsinless photoreceptors. In transgenic
      Xenopus, a C-terminally truncated peripherin/rds-GFP fusion predominantly
      localized to its normal location within disc rims. In developing rds mice, rom-1
      accumulated primarily in distal ciliary membranes. CONCLUSIONS: Peripherin/rds
      transport and localization are polarized to the site of outer segment
      morphogenesis before disc formation in developing photoreceptors. Peripherin/rds
      and rom-1 trafficking is maintained in rhodopsin-knockouts, suggesting that rim
      proteins and rhodopsin have separate transport pathways. The presence of
      truncated peripherin/rds-GFP in the outer segment supports previous evidence that
      peripherin/rds mice form homotetramers for outer segment targeting. The finding
      that rom-1 transports to the outer segment domain in rds mice suggests that rom-1
      may possess its own sorting and transport signals.

PMID- 16639029
TI  - Fas signaling induces raft coalescence that is blocked by cholesterol depletion
      in human RPE cells undergoing apoptosis.
AB  - PURPOSE: To investigate whether the signaling events occurring in Fas-mediated
      apoptosis alter raft membrane formation in human RPE cells. METHODS: Formation of
      lipid rafts in cultured human retinal pigment epithelial cells (ARPE-19) was
      studied by confocal microscopy, with fluorescein-labeled cholera toxin subunit B
      binding protein (BODIPY)-labeled ganglioside GM1 lipid after Fas-L induction of
      apoptosis. Apoptosis was assessed by fluorescein-labeled annexin V detection of
      phosphatidylserine externalization and quadrant analysis with flow cytometry.
      Membrane rafts were localized into membrane vesicles by passing BODIPY-labeled
      GM1 RPE cells through a 2-microm-pore polycarbonate membrane using an extruder
      device. The labeled fractions, containing vesicles enriched in GM1, were detected
      by flow cytometry and then analyzed for the presence of Fas protein. RESULTS:
      Differential punctate staining of membrane rafts was demonstrated in normal and
      FasL-induced apoptotic human ARPE-19 cells in culture by confocal microscopy,
      using cholera toxin B and GM1 labeling of extruded vesicles. The lipid raft
      associated vesicles were derived by plasma membrane dissociation, via a newly
      developed whole-cell extrusion technique that produced 2-microm vesicles with
      both GM1 lipid and Fas protein abundance enriched in a subpopulation of the
      membrane-derived vesicles. The amount of Fas protein in the vesicles containing
      raft domains markedly increased in FasL-treated cells. Treatment of human ARPE 19
      cells with methyl beta-cyclodextrin after FasL induction of apoptosis resulted in
      cellular cholesterol depletion and markedly reduced the incidence of Fas-receptor
      localization in GM1 rafts. CONCLUSIONS: Human ARPE-19 cells in culture contain
      membrane rafts with apoptotic signaling effectors uniformly distributed in the
      native state. The cells stimulated to undergo apoptosis appear to use membrane
      rafts in the death-signaling process by mobilization of rafts to localized
      regions of the membrane that are now enriched with apoptotic signaling effectors.
      Fas signaling induces apoptotic raft formation that results in polar
      condensation, or capping, of the rafts in the late stages of apoptosis. A novel
      extrusion technique is described that allows localization and enrichment of rafts
      into membrane vesicles, which can be assayed by flow cytometry. Cholesterol
      depletion, after Fas ligand activation of apoptosis, reduced raft formation in
      cells induced to undergo apoptosis. Therapeutic implications for the treatment of
      retinal disorders are discussed.

PMID- 16639030
TI  - Effect of curcumin on proliferation of human retinal endothelial cells under in
      vitro conditions.
AB  - PURPOSE: To investigate the effect of high glucose on the proliferation of human
      retinal endothelial cells (HRECs) and to elucidate the possible mechanisms of
      antiangiogenic activity of curcumin, a diferuloylmethane. METHODS: Human retinal
      endothelial cells were isolated from the retinal tissue obtained from human
      donors and the culture system was established. The effect of curcumin on the
      proliferation of primary HRECs in the presence of low and high glucose was
      measured by MTT and thymidine uptake assays. Apoptosis was assessed by TUNEL
      assay and other adjuvant tools. Effect of curcumin on phorbol ester stimulated
      intracellular reactive oxygen species (ROS) generation in high glucose conditions
      was assessed by fluorescence assay. Finally, semiquantitative RT-PCR and Western
      blot analysis was performed to measure VEGF mRNA production and VEGF induced PKC
      betaII translocation, respectively in the presence and absence of curcumin.
      RESULTS: HREC culture was established successfully at passages 3 and 4 at 80%
      confluence. Curcumin effectively inhibited endothelial cell proliferation in a
      dose-dependent manner. At a concentration of 10 microM, curcumin significantly
      inhibited HREC proliferation in high-glucose-treated cells, as verified by both
      MTT and thymidine uptake assay. Curcumin also showed a significant (P = 0.03)
      reduction of intracellular ROS generation in HRECs. RNA expression studies showed
      that curcumin had an inhibitory effect on the glucose-induced VEGF mRNA
      expression. In addition, VEGF-mediated, membrane-associated changes in the PKC
      betaII translocation in HRECs was inhibited by 31% on treatment with 10 microM
      curcumin. CONCLUSIONS: These data suggest an underlying mechanism whereby
      curcumin induces the apoptosis in HRECs by the regulation of intracellular ROS
      generation, VEGF expression and release, and VEGF-mediated PKC-betaII
      translocation.

PMID- 16639031
TI  - Effects of low AIPL1 expression on phototransduction in rods.
AB  - PURPOSE: To investigate the impact of aryl hydrocarbon receptor-interacting
      protein-like (AIPL)-1 on photoreception in rods. METHODS: Photoresponses of mouse
      rods expressing lowered amounts of AIPL1 were studied by single-cell and
      electroretinogram (ERG) recordings. Phototransduction protein levels and
      enzymatic activities were determined in biochemical assays. Ca2+ dynamics were
      probed with a fluorescent dye. Comparisons were made to rods expressing mutant
      Y99C guanylate cyclase activating protein (GCAP)-1, to understand which effects
      arose from elevated dark levels of cGMP and Ca2+. RESULTS: Except for PDE,
      transduction protein levels were normal in low-AIPL1 retinas, as were guanylate
      cyclase (GC), rhodopsin kinase (RK), and normalized phosphodiesterase (PDE)
      activities. Y99C and low-AIPL1 rods were more sensitive to flashes than normal,
      but flash responses of low-AIPL1 rods showed an abnormal delay, reduced rate of
      increase, and longer recovery not present in Y99C rod responses. In addition, low
      AIPL1 rods but not Y99C rods failed to reach the normal light-induced minimum in
      Ca2+ concentration. CONCLUSIONS: Reduced AIPL1 delayed the photoresponse,
      decreased its amplification constant, slowed a rate-limiting step in its
      recovery, and limited the light-induced decrease in Ca2+. Not all changes were
      attributable to decreased PDE or to elevated cGMP and Ca2+ in darkness.
      Therefore, AIPL1 directly or indirectly affects more than one component of
      phototransduction.

PMID- 16639033
TI  - Dopaminergic neurons reduced to silence by oxidative stress: an early step in the
      death cascade in Parkinson's disease?
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder that is most
      often sporadic, but in some cases it can be inherited as a simple Mendelian
      trait. The most important pathological feature of the disease is the death of
      brainstem dopaminergic neurons in the substantia nigra, which leads to
      characteristic motor symptoms. The etiology of PD remains unknown, but
      mitochondrial dysfunction and oxidative stress may contribute actively to the
      underlying pathomechanism. New studies suggest that K(ATP) channel activation may
      represent a downstream effector of these two cellular anomalies.

PMID- 16639034
TI  - Oxidative modification of protein tyrosine phosphatases.
AB  - Our understanding of the biological effects of reactive oxidants has deepened
      considerably over the past decade. Less the indiscriminate loose cannons we
      previously imagined, both superoxide and hydrogen peroxide appear to target
      relatively specific molecular structures. Perhaps the most consequential of such
      targets within proteins is the reduced sulfhydryl of cysteine residues. Because
      protein tyrosine phosphatases (PTPs) all harbor an absolutely conserved catalytic
      cysteine residue, oxidation of this residue inactivates PTPs, rendering tyrosine
      kinase signaling pathways highly sensitive to the local redox environment.
      Therefore, tyrosine phosphorylation-dependent signaling involving receptor
      tyrosine kinases, mitogen-activated protein kinases, Abl, Src, and Pyk2 is known
      to be initiated or amplified by reactive oxidants. We describe a nonradioisotopic
      method that discriminates between reduced and oxidatively modified tyrosine
      phosphatases, thus facilitating studies that may mechanistically link oxidant
      activity with specific signaling pathways.

PMID- 16639035
TI  - Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to
      aging and radical-caused diseases.
AB  - Mitochondria-generated reactive oxygen species have been implicated as a common
      feature that connects aging of organisms and age-related diseases. Efficient
      elimination of these radicals by antioxidants correlates with increased life
      span. Understanding how the mitochondrion signals to the nucleus to regulate
      antioxidant proteins might be a key to aging processes and treatment of human
      diseases.

PMID- 16639036
TI  - The cover. Henry Pelham (Boy With a Squirrel).

PMID- 16639038
TI  - Scientists probe role of genes, environment in Parkinson disease.

PMID- 16639037
TI  - A piece of my mind. Dog pals.

PMID- 16639039
TI  - Avian flu risk to humans probed: viral adaptation to human cells would aid
      spread.

PMID- 16639040
TI  - Mixed success found for avian flu vaccine.

PMID- 16639041
TI  - Effects of stress on children examined.

PMID- 16639042
TI  - Prognostic value of B-type natriuretic peptide in unstable coronary artery
      disease.

PMID- 16639043
TI  - Excess dosing of antithrombotic therapy in non-ST-segment elevation acute
      coronary syndromes.

PMID- 16639044
TI  - Excess dosing of antithrombotic therapy in non-ST-segment elevation acute
      coronary syndromes.

PMID- 16639045
TI  - Smallpox vaccinations and adverse events.

PMID- 16639046
TI  - Excess dosing of antithrombotic therapy in non-ST-segment elevation acute
      coronary syndromes.

PMID- 16639047
TI  - Detection of vaccinia DNA in the blood following smallpox vaccination.

PMID- 16639048
TI  - Pacemaker and ICD generator malfunctions: analysis of Food and Drug
      Administration annual reports.
AB  - CONTEXT: Pacemakers and implantable cardioverter-defibrillators (ICDs) are
      complex medical devices proven to reduce mortality in specific high-risk patient
      populations. It is not known if increasing device complexity is associated with
      decreased reliability. OBJECTIVES: To analyze postapproval annual reports
      submitted to the US Food and Drug Administration (FDA) by manufacturers of
      pacemakers and ICDs to determine the reported number and rate of pacemaker and
      ICD malfunctions and to assess trends in device performance. DESIGN AND SETTING:
      Pacemaker and ICD annual reports submitted to the FDA for the years 1990-2002
      were reviewed. A pacemaker or ICD generator was defined as having malfunctioned
      if it was explanted due to an observed malfunction, returned to the manufacturer,
      and confirmed by the manufacturer to be functioning inappropriately. Leads and
      biventricular devices were not included in the study. Deaths were attributed to
      device malfunction only if they were witnessed, the malfunction immediately led
      to the death, and the malfunction was confirmed by the manufacturer. MAIN OUTCOME
      MEASURES: Number of implanted pacemaker and ICD generators; number of reported
      malfunctions; and annual malfunction replacement rates. Generator malfunction
      replacement rates were defined as the annual number of replacements due to
      confirmed malfunction divided by the annual number of implants. RESULTS: During
      the study period, 2.25 million pacemakers and 415,780 ICDs were implanted in the
      United States. Overall, 17,323 devices (8834 pacemakers and 8489 ICDs) were
      explanted due to confirmed malfunction. Battery/capacitor abnormalities (4085
      malfunctions [23.6%]) and electrical issues (4708 malfunctions [27.1%]) accounted
      for half of the total device failures. The annual pacemaker malfunction
      replacement rate per 1000 implants decreased significantly during the study, from
      a peak of 9.0 in 1993 to a low of 1.4 in 2002 (P = .006 for trend). In contrast,
      the ICD malfunction replacement rate per 1000 implants, after decreasing from
      38.6 in 1993 to 7.9 in 1996, increased markedly during the latter half of the
      study, peaking in 2001 at 36.4 (P = .04 for trend). More than half of the
      reported ICD malfunctions occurred in the last 3 years of the study. Overall, the
      annual ICD malfunction replacement rate was significantly higher than the
      pacemaker malfunction replacement rate (mean [SD], 20.7 [11.6] vs 4.6 [2.2]
      replacements per 1000 implants; P<.001; rate ratio, 5.9 [95% confidence interval,
      2.7-9.1]). Sixty-one deaths (30 pacemaker patients, 31 ICD patients) were
      attributable to device malfunction. CONCLUSIONS: This study demonstrates that
      thousands of patients have been affected by pacemaker and ICD malfunctions, the
      pacemaker malfunction replacement rate has decreased, the ICD malfunction
      replacement rate increased during the latter half of the study, and the ICD
      malfunction replacement rate is significantly higher than that for pacemakers.
      Although pacemakers and ICDs are important life-sustaining devices that have
      saved many lives, careful monitoring of device performance is still required.

PMID- 16639049
TI  - Complications associated with implantable cardioverter-defibrillator replacement
      in response to device advisories.
AB  - CONTEXT: Recent implantable cardioverter-defibrillator (ICD) advisories and
      recalls have caused management dilemmas for physicians, particularly because
      there are no specific guidelines or data on outcomes from current management
      strategies. The risk of ICD generator replacement has not been assessed in this
      population. OBJECTIVE: To determine the complication rate associated with ICD
      generator replacement for the current ICD advisories. DESIGN AND SETTING:
      Seventeen ICD implanting centers in Canada were surveyed to assess complication
      rates as a result of generator replacements because of ICD advisories from
      October 2004 to October 2005. MAIN OUTCOME MEASURE: Complications associated with
      elective ICD generator replacement for current device advisories. RESULTS: At the
      17 surveyed centers, 2915 patients had recall devices, including 533 (18.3%) who
      had advisory ICDs replaced a mean (SD) of 26.5 (11.5) months after their initial
      implant. Of these patients, 66% had a secondary prevention ICD, and 45% had
      received a previous appropriate shock. During a mean (SD) of 2.7 (2.8) months'
      follow-up after ICD generator replacement, complications occurred in 43 patients
      (8.1%). Major complications attributable to advisory device replacement requiring
      reoperation occurred in 31 patients (5.8%), with death in 2 patients after
      extraction for pocket infection. Minor complications occurred in 12 patients
      (2.3%). There were 3 (0.1%) advisory-related device malfunctions reported,
      without clinical consequences. CONCLUSIONS: ICD generator replacement in patients
      with advisory devices is associated with a substantial rate of complications,
      including death. These complications need to be considered in the development of
      guidelines determining the appropriate treatment of patients with advisory
      devices.

PMID- 16639050
TI  - Association between hospital process performance and outcomes among patients with
      acute coronary syndromes.
AB  - CONTEXT: Selected care processes are increasingly being used to measure hospital
      quality; however, data regarding the association between hospital process
      performance and outcomes are limited. OBJECTIVES: To evaluate contemporary care
      practices consistent with the American College of Cardiology/American Heart
      Association (ACC/AHA) guideline recommendations, to examine how hospital
      performance varied among centers, to identify characteristics predictive of
      higher guideline adherence, and to assess whether hospitals' overall composite
      guideline adherence was associated with observed and risk-adjusted in-hospital
      mortality rates. DESIGN, SETTING, AND PARTICIPANTS: An observational analysis of
      hospital care in 350 academic and nonacademic US centers of 64,775 patients
      enrolled in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina
      Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA
      Guidelines) National Quality Improvement Initiative between January 1, 2001, and
      September 30, 2003, presenting with chest pain and positive electrocardiographic
      changes or cardiac biomarkers consistent with non-ST-segment elevation acute
      coronary syndrome (ACS). MAIN OUTCOME MEASURES: Use of 9 ACC/AHA class I
      guideline-recommended treatments and the correlation among hospitals' use of
      individual care processes as well as overall composite adherence rates. RESULTS:
      Overall, the 9 ACC/AHA guideline-recommended treatments were adhered to in 74% of
      eligible instances. There was modest correlation in hospital performance among
      the individual ACS process metrics. However, composite adherence performance
      varied widely (median [interquartile range] composite adherence scores from
      lowest to highest hospital quartiles, 63% [59%-66%] vs 82% [80%-84%]). Composite
      guideline adherence rate was significantly associated with in-hospital mortality,
      with observed mortality rates decreasing from 6.31% for the lowest adherence
      quartile to 4.15% for the highest adherence quartile (P<.001). After risk
      adjustment, every 10% increase in composite adherence at a hospital was
      associated with an analogous 10% decrease in its patients' likelihood of in
      hospital mortality (adjusted odds ratio, 0.90; 95% confidence interval, 0.84
      0.97; P<.001). CONCLUSION: A significant association between care process and
      outcomes was found, supporting the use of broad, guideline-based performance
      metrics as a means of assessing and helping improve hospital quality.

PMID- 16639051
TI  - Financial conflict of interest disclosure and voting patterns at Food and Drug
      Administration Drug Advisory Committee meetings.
AB  - CONTEXT: In January 2002, the US Food and Drug Administration (FDA) issued a
      draft guidance requiring more detailed financial conflict of interest disclosure
      at advisory committee meetings. OBJECTIVES: To characterize financial conflict
      disclosures at drug-related meetings, and to assess the relationship between
      conflicts and voting behavior at meetings that considered specific products.
      DESIGN AND SETTING: Cross-sectional study using agendas and transcripts from all
      FDA Drug Advisory Committee meetings (2001-2004) listed on the FDA Web site. MAIN
      OUTCOME MEASURES: Conflict rates, type, and size. The relationship between having
      a conflict and voting in favor of the index drug was described for each voter
      using Mantel-Haenszel relative risks and Monte Carlo simulations; Spearman rho
      was used for a meeting-level analysis comparing rates of conflict with voting
      patterns. The impact of the removal of persons with conflicts of interest on the
      vote margins was also evaluated. RESULTS: A total of 221 meetings held by 16
      advisory committees were included in the study. In 73% of the meetings, at least
      1 advisory committee member or voting consultant disclosed a conflict; only 1% of
      advisory committee members were recused. For advisory committee members (n =
      1957) and voting consultants combined (n = 990), 28% (n = 825) disclosed a
      conflict. The most commonly specified conflicts were consulting arrangements,
      contracts/grants, and investments. Nineteen percent of consulting arrangements
      involved over 10,000 dollars, 23% of contracts/grants exceeded 100,000 dollars,
      and 30% of investments were over 25,000 dollars. The meeting-level analysis did
      not show a statistically significant relationship between conflict rates ("index
      conflict," "competitor conflict," or "any conflict") and voting patterns, but a
      weak, statistically significant positive relationship was apparent for competitor
      conflict and any conflict in the Mantel-Haenszel analyses. The Monte Carlo
      analyses produced similar findings in the competitor conflict analysis only. In
      all 3 conflict categories, the exclusion of advisory committee members and voting
      consultants with conflicts would have produced margins less favorable to the
      index drug in the majority of meetings, but this would not have changed whether
      the majority favored or opposed the drug. CONCLUSIONS: Disclosures of conflicts
      of interest at drug advisory committee meetings are common, often of considerable
      monetary value, and rarely result in recusal of advisory committee members. A
      weak relationship between certain types of conflicts and voting behaviors was
      detected, but excluding advisory committee members and voting consultants with
      conflicts would not have altered the overall vote outcome at any meeting studied.

PMID- 16639052
TI  - Pacemaker and ICD generator reliability: meta-analysis of device registries.
AB  - CONTEXT: Despite there being millions of pacemaker and implantable cardioverter
      defibrillator (ICD) generator implants worldwide, little is known about device
      reliability. OBJECTIVES: To perform a meta-analysis of prospective pacemaker and
      ICD registries to determine annual rates of pacemaker and ICD malfunction and to
      identify trends in these rates. DATA SOURCES: MEDLINE (January 1966 to April
      2005), the Cochrane Central Register of Controlled Trials (through second quarter
      2005), the Cochrane Database of Systematic Reviews (through second quarter 2005),
      and a bibliographic review of secondary sources. Search terms included pacemaker,
      artificial; defibrillators, implantable; registries; performance; and
      malfunction. STUDY SELECTION: Eligible registries were prospective; reported the
      number of patients with pacemaker, ICD, or both; and allowed determination of the
      annual number of device malfunctions. Of 1007 references screened, 3 registries
      meeting the selection criteria were identified and included 2.1 million pacemaker
      person-years and 14,821 ICD person-years of observation. DATA EXTRACTION:
      Included the annual number of patients with pacemakers and ICDs at risk of device
      failure and the annual number of generator malfunctions (1983-2004 for
      pacemakers, 1988-2004 for ICDs). A device malfunction was defined as an integral
      component failure that required device explantation prior to reaching elective
      replacement. Failures of pacemaker and ICD electrodes were not included in the
      study. DATA SYNTHESIS: There were 2981 pacemaker and 384 ICD generator
      malfunctions. Pacemaker reliability improved markedly during the 1980s (P for
      trend <.001) and the pacemaker malfunction rate remained low during the remainder
      of the study. Implantable cardioverter-defibrillator reliability improved during
      the first 10 study years (P for trend <.001). From 1998-2002, however, the ICD
      malfunction rate increased more than 4-fold (P for trend <.001), before
      decreasing substantially in the latter 2 years of the study. Overall, the mean
      (SE) annual ICD malfunction rate was about 20-fold higher than the pacemaker
      malfunction rate (26.5 [3.8] vs 1.3 [0.1] malfunctions per 1000 person-years,
      P<.001). Battery malfunctions were the most common cause of device failure.
      CONCLUSIONS: Pacemaker reliability has improved markedly. In contrast, after more
      than a decade of improving device reliability, the ICD malfunction rate
      transiently increased before experiencing substantial reductions in the latter 2
      study years. Whether increasing device sophistication accounts for the observed
      decrease in reliability is not known. Continued monitoring of pacemaker and ICD
      performance is required.

PMID- 16639053
TI  - Using clinical guidelines designed for older adults with diabetes mellitus and
      complex health status.
AB  - Increasingly, adults are living to an advanced age. While many enjoy good health,
      nearly 50% of adults older than 65 years have 3 or more chronic medical
      conditions. Furthermore, within any age-sex cohort, older adults exhibit widely
      heterogeneous health status--ranging from robust to frail. This heterogeneity and
      individual medical complexity makes care for older patients particularly
      challenging and requires both careful medical judgment and a clear understanding
      of the patient's personal values and goals. Most current health care guidelines
      are disease-specific and do not address this complexity and heterogeneity, thus
      limiting their utility for guiding physicians in the care of older adult
      patients. The "Guidelines for Improving the Care of Older Persons With Diabetes
      Mellitus" are the first guidelines to specifically address this complexity and
      provide guidance to physicians who must prioritize therapies and goals for older
      adults with diabetes, comorbid medical conditions, and geriatric syndromes. By
      providing a rationale for prioritizing recommendations and the inclusion of
      geriatric syndromes that impact the patient's overall health and diabetic care,
      these guidelines may serve as a model for the development of other guidelines
      targeting older adults with complex health status.

PMID- 16639054
TI  - Physician-assisted suicide: a legitimate medical practice?

PMID- 16639055
TI  - Pacemaker and ICD malfunction--an incomplete picture.

PMID- 16639062
TI  - JAMA patient page. Implantable cardioverter-defibrillators.

PMID- 16639063
TI  - Lack of enteral nutrition delays nuclear factor kappa B activation in peritoneal
      exudative cells in a murine glycogen-induced peritonitis model.
AB  - BACKGROUND: Early enteral nutrition is associated with a lower incidence of
      intraabdominal abscess in severely injured patients than parenteral nutrition
      (PN). We explored the underlying mechanisms by examining the influence of
      nutrition route on nuclear factor kappaB (NFkappaB) activation in peritoneal
      exudative cells (PECs) and peritoneal cytokine levels. METHODS: Thirty male
      Institute Cancer Research mice were randomized to chow (n = 10), IV PN (n = 10),
      or intragastric (IG) PN (n = 10) and fed for 5 days. PECs were harvested at 2 or
      4 hours after intraperitoneal injection of 2 mL of 1% glycogen. Intranuclear
      NFkappaB activity in PECs was examined by laser scanning cytometry. Cytokine
      (tumor necrosis factor-alpha [TNF-alpha], macrophage inflammatory protein-2 [MIP
      2], interleukin-10 [IL-10]) levels in peritoneal lavaged fluid were determined by
      enzyme-linked immunosorbent assay. RESULTS: Intranuclear NFkappaB at 2 hours was
      significantly higher in the chow and IG-PN groups than in the IV-PN group. TNF
      alpha and IL-10 levels of the chow group were significantly higher than those of
      IV-PN mice at 2 hours, whereas those of IG-PN mice were midway between those of
      the chow and IV-PN groups. MIP-2 was significantly higher in the chow group than
      in the IG-PN and IV-PN mice at 2 hours. TNF-alpha levels correlated positively
      with intranuclear NFkappaB activity in PECs. CONCLUSIONS: Enteral nutrition may
      improve peritoneal defense by preserving early NFkappaB activation in PECs and
      cytokine responses.

PMID- 16639064
TI  - Hypertaurinemia in bile duct-ligated rats after surgery: the effect of gut
      endotoxin restriction on organ fluxes and oxidative status.
AB  - Surgery in obstructive jaundice is associated with complications related to gut
      derived endotoxemia. The organs involved in these complications, including liver,
      kidneys, and gut, are important in the metabolism of taurine, which is implicated
      in bile acid conjugation and has antioxidative effects. Taurine organ metabolism
      and liver oxidative status were studied in bile duct-ligated rats (BDL) after
      laparotomy. Oral cholestyramine treatment inhibits gut-derived endotoxemia and
      was used to evaluate the role of endotoxin. In BDL rats, postoperative plasma
      taurine levels were higher compared with SHAM (p < .0001). Cholestyramine
      treatment reduced plasma taurine in BDL rats (p < .005), but levels remained
      higher compared with SHAM groups (p < .0001). In contrast to a liver uptake of
      taurine in SHAM rats, a release from livers of BDL rats was found (p < .005).
      Cholestyramine treatment in BDL rats resulted in a liver uptake of taurine (p <
      .05 vs BDL). A higher uptake of taurine by the kidneys was found in both BDL
      animals after surgery and SHAM controls (p < .005); however, cholestyramine had
      no effect. A release of taurine from the gut was found in the SHAM groups, which
      was reversed in both BDL groups (p < .01). Cholestyramine lowered the elevated
      levels of hepatic enzymes in BDL rats (ALT and AST: p < .05). Total liver
      glutathione levels were lower in BDL rats (p < .0001) compared with SHAM groups,
      and cholestyramine significantly attenuated this decrease (p < .01). Liver
      malondialdehyde levels were higher in BDL rats compared with SHAM (p < .01),
      whereas cholestyramine completely prevented this increase in lipid peroxidation
      (p < .0001). Hypertaurinemia in BDL rats after surgery is most likely explained
      by reduced bile acid conjugation and hepatocellular leakage. Cholestyramine
      treatment reduced hepatocellular damage by inhibiting gut-derived endotoxemia,
      and reversed the release of taurine from the jaundiced liver into an uptake and
      consequently lowered plasma taurine levels. This uptake may contribute to the
      improved antioxidant status in cholestyramine-treated BDL rats.

PMID- 16639065
TI  - Whole-body protein metabolism in chronic heart failure: relationship to anabolic
      and catabolic hormones.
AB  - BACKGROUND: Patients with chronic heart failure frequently experience profound
      wasting during the course of the disease, a condition termed cardiac cachexia.
      Although protein is the primary structural and functional component of most
      tissues, few studies have examined the effect of heart failure on protein
      metabolism. Moreover, no study has assessed the relationship of protein turnover
      to hormonal alterations thought to promote cachexia. Thus, our goal was to
      determine if whole-body protein metabolism is altered in heart failure patients
      and to assess the relationship of protein kinetics to circulating levels of
      anabolic and catabolic hormones. METHODS: We measured whole-body protein
      metabolism using 13C-leucine, body composition, and circulating anabolic and
      catabolic hormone levels in 10 patients with chronic heart failure and 11 elderly
      controls. RESULTS: No differences in leucine rate of appearance, oxidation, or
      nonoxidative disposal were noted between heart failure patients and controls.
      However, in a subgroup of patients characterized by increased resting energy
      expenditure for their metabolic body size (n = 4; > or = 20% above that predicted
      from fat-free mass), leucine rate of appearance (mean +/- SE; 146 +/- 6
      micromol/min), an index of protein breakdown, tended to be higher compared with
      patients with normal resting energy expenditure (n = 5; 120 +/- 8 micromol/min)
      and controls (127 +/- 4 micromol/min; p = .06). Alterations in anabolic/catabolic
      hormone balance did not explain increased protein breakdown in this subgroup, and
      no correlations were found between hormone levels and protein breakdown in the
      heart failure group as a whole. In contrast, increased circulating interleukin-6
      soluble receptor (r = 0.829; p < .01) and reduced insulin-like growth factor-I (r
      =-.751; p < .05) levels were related to greater rates of leucine oxidation in
      heart failure patients. CONCLUSION: Our results demonstrate that, although
      increased protein turnover is not a generalized feature of heart failure, there
      is a subgroup of patients characterized by resting hypermetabolism and increased
      protein breakdown. Moreover, hormonal alterations related to the heart failure
      syndrome were related to increased protein oxidation.

PMID- 16639066
TI  - Liver failure is uncommon in adults receiving long-term parenteral nutrition.
AB  - BACKGROUND: Abnormal liver enzymes and endstage liver disease are reported to
      occur in 25%-100% and 15%-40% of adult patients receiving long-term parenteral
      nutrition (PN), respectively. The purpose of this historic cohort study was to
      investigate the incidence of and possible factors leading to the development of
      liver disease in our large home PN population. METHODS: All patients on home PN
      for at least 6 months from July 1991 through June 2002 were eligible. Patients
      were excluded if they had active malignancy, underlying liver disease, or
      exposure to a hepatotoxin. The presence of PN-associated liver disease was only
      considered if test results were elevated on more than 1 occasion over at least 6
      or more months. The severity of liver-associated enzymes was based on the degree
      of elevation and was stratified as mild (<2 times normal), moderate (2-5 times
      normal), and severe (>5 times normal). Severe liver dysfunction was defined as
      having all of the following criteria: total bilirubin >3 mg/dL; albumin <3.2
      g/dL; and prothrombin time >3 seconds prolonged. A cumulative logit model was
      used to compare age, gender, underlying disease, PN indication, and PN formulas
      in patients with normal vs abnormal laboratory test results. RESULTS: Two hundred
      eight patients received PN for more than 6 months, 36 had exclusion criteria, and
      10 could not be analyzed, because of incomplete laboratory test results, leaving
      162 in the study group. The average PN duration was 2.14 +/- 2.19 years (maximum,
      10.28 years). Abnormal liver tests occurred in 154 patients, with most having a
      moderate elevation of alkaline phosphatase or aspartate aminotransferase; severe
      liver dysfunction occurred in 7 patients; 1 patient had completely normal liver
      enzymes. On average, patients received a PN formula that was high in amino acids
      (1.45 +/- 0.65 g/kg/d), modest in energy (24.7 +/- 13.4 kcal/kg/d), and in most
      cases with enough lipid emulsion to meet essential fatty acid requirements (0.28
      +/- 0.25 g/kg/d). Only female gender was found to be associated with a greater
      likelihood of liver failure (p = .02). There was a trend toward a greater amount
      of total calories, dextrose calories, and duration of PN exposure leading to the
      development of severe liver dysfunction. CONCLUSIONS: When long-term PN is given
      with a modest amount of total energy and a minimal amount of lipid emulsion,
      abnormal liver enzymes are common, but severe liver dysfunction is unusual.

PMID- 16639067
TI  - A new graduated dosing regimen for phosphorus replacement in patients receiving
      nutrition support.
AB  - BACKGROUND: Hypophosphatemia is a common metabolic complication in patients
      receiving specialized nutrition support. We changed our previously reported
      dosing algorithm because the low dose no longer appeared to be effective at
      increasing serum phosphorus concentrations. The purpose of this study was to
      evaluate the safety and efficacy of a revised weight-based phosphorus-dosing
      algorithm in critically ill trauma patients receiving specialized nutrition
      support. METHODS: Seventy-nine adult trauma patients with hypophosphatemia (serum
      phosphorus concentration < or = 0.96 mmol/L) receiving nutrition support received
      an IV dose of phosphorus on day 1 according to the serum concentration of
      phosphorus: 0.73-0.96 mmol/L (0.32 mmol/kg, low dose), 0.51-0.72 mmol/L (0.64
      mmol/kg, moderate dose), and < or = 0.5 mmol/L (1 mmol/kg, high dose). The IV
      phosphorus bolus dose was administered at 7.5 mmol/hour. Generally, patients with
      a serum potassium concentration <4 mmol/L received potassium phosphate and
      patients with a serum potassium concentration > or = 4 mmol/L received sodium
      phosphate. Patients who still had hypophosphatemia on day 2 were dosed using the
      new dosing algorithm by the nutrition support service according to that day's
      serum concentration of phosphorus, or empirically by the trauma service. RESULTS:
      Of the 79 patients studied, 57 were male and 22 were female with a mean age of
      44.8 +/- 20.6 years. Mean Injury Severity Scores and APACHE-II scores were 27.1
      +/- 11.6 and 15.2 +/- 6.8, respectively. There was no difference in baseline
      characteristics among the 3 dosing groups. Of the 79 patients, 34 received the
      low dose, 30 received the moderate dose, and 15 received the high dose of
      phosphorous. Mean serum phosphorous concentrations on day 2 were significantly
      increased in the moderate-dosed group (0.64 +/- 0.06 to 0.77 +/- 0.22 mmol/L, p <
      .05) and high-dosed group (0.38 +/- 0.06 to 0.93 +/- 0.32 mmol/L, p < .01),
      respectively, when compared with day 1. Mean serum phosphorus concentrations were
      normal in all 3 groups on day 3. Serum concentrations of magnesium, sodium, and
      potassium, as well as arterial pH, were stable across the study. Mean
      concentrations of ionized calcium were not significantly different in any of the
      3 dosing groups across the study period. CONCLUSIONS: This weight-based
      phosphorus-dosing algorithm is safe for use in critically ill patients receiving
      nutrition support. The moderate and severe-dose regimens effectively increase
      serum phosphorus concentrations.

PMID- 16639068
TI  - Problems experienced by patients receiving parenteral nutrition at home: results
      of an open interview study.
AB  - BACKGROUND: Home parenteral nutrition (HPN) is offered to patients who are unable
      to absorb sufficient nourishment from normal oral food intake or tube feeding.
      Major causes include severe motility disorders and limited resorption surface in
      the small intestine. HPN is a lifesaving therapy but has severe consequences on
      daily life. The aim of this study was to make an inventory of the problems
      experienced by patients receiving HPN. METHODS: Open interviews were held with 48
      patients from the 2 major centers for HPN in the Netherlands, centered around the
      question: Which 3 HPN problems have the most severe impact on your daily life?
      Data were analyzed using content analysis. RESULTS: The respondents mentioned 7
      central problems: negative emotions, physical problems, social limitations,
      dependence on others, incapability, complications, and patient-care provider
      problems. In addition, practical problems were mentioned: sleeping problems,
      financial problems, and the "hospital atmosphere" at home. The latter issues
      formed less of a problem for the patients. CONCLUSION: The main underlying
      elements in the lives of many HPN patients appeared to be loss, longing, and
      grief. In contrast, a smaller proportion of the patients expressed that they had
      clearly adapted to life with HPN. By means of the HPN, they were still alive and
      enjoying all the things they could still do.

PMID- 16639069
TI  - The influence of early supplementation of parenteral nutrition on quality of life
      and body composition in patients with advanced cancer.
AB  - BACKGROUND: According to current evidence, most organizations, including the
      American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), do not
      recommend the routine use of artificial nutrition for patients with cancer.
      Despite the recommendation for parenteral nutrition (PN), data for early PN
      supplementation (PNS) in patients with an advanced malignancy are extremely
      limited, especially in terms of the affects on nutrition outcomes, body
      composition, and quality of life (QOL), as well as effects on oncologic outcomes.
      The aim of the study was to evaluate the effect of PNS on body composition and
      the quality of life in patients with advanced malignancies. METHODS: One hundred
      fifty-two consecutive patients with advanced cancer were prospectively randomized
      to either use of oral enteral nutrition supplement (PN-) or use of oral enteral
      nutrition supplement plus supplemental PN (PN+). Body weight, body mass index
      (BMI), and caloric intake were assessed, and hemoglobin (g/dL) and serum albumin
      (g/L) were measured. Body composition was assessed by body impedance analysis
      (BIA), and QOL was evaluated by European Organization for Research and Treatment
      of Cancer (EORTC) QLQ-C30 questionnaire every 6 weeks. RESULTS: No significant
      differences were evident at baseline between the 2 groups for age, gender,
      medical diagnosis, weight, BMI, or QOL. A statistically significant difference in
      mean BMI was observed by week 48 for the PN+ group (PN+ = 21.9, PN-= 20.5, p =
      .0149), by week 6 in mean body cell mass (PN+ = 55%, PN-= 50,1%, p < .001), mean
      albumin (PN+ = 40.2 g/L, PN-= 36.2 g/L, p = .015), mean QOL (PN+ = 55.7, PN-=
      50.9, p = .035). The cumulative survival rate was significantly greater in the
      PN+ group (p < .0001). CONCLUSIONS: According to the positive effect of
      supplemental PN on survival, body composition, and QOL, additional controlled
      studies must be conducted to confirm these findings.

PMID- 16639070
TI  - Application criteria of enteral nutrition in patients with anorexia nervosa:
      correlation between clinical and psychological data in a "lifesaving" treatment.
AB  - BACKGROUND: Data and research increasingly point to multiple factors in the
      genesis of eating-behavior disorders, but the lack of a clear etiological
      definition prevents a unique therapeutic or prognostic approach from being
      defined. Therapeutic approaches, as well as scientific research, have separately
      analyzed the psychological aspects and the clinical-nutrition aspects without
      integrating the variables or correlating clinical and psychological data. This
      work has several goals because it aims at considering the problem from the 2
      different perspectives. Psychological and clinical variables are analyzed both
      separately and together in order to assess (a) the minimal criteria to define a
      cure as "lifesaving" and submit a patient to artificial nutrition; (b) the kind
      of implementation artificial nutrition should follow; (c) which indicators of the
      efficacy of artificial nutrition must be taken into account; (d) the results in
      nutrition terms that may be obtained during the follow-up; (e) if artificial
      nutrition may be used as a therapeutic tool; (f) if there are any psychological
      effects after artificial nutrition; (g) if there are any effects due to the
      patients' age; and (h) the correlation between the psychological profile of a
      patient and the acceptance of the nutrition treatment. METHODS: Several
      psychological and pharmacologic variables, together with clinical and
      anthropometric data and blood chemical values, were all considered. CONCLUSIONS:
      Besides defining minimal criteria for a "lifesaving" cure and proposing 2 ad hoc
      scales for the assessment of patients' subjective willingness toward feeding and
      for the objective measurement of feeding itself, clinical data and correlations
      with psychological data evidenced the importance of artificial nutrition and
      specifically of enteral nutrition as a therapeutic tool, allowing us to define
      the modalities of implementation of enteral nutrition. Results show that, because
      enteral nutrition did not deteriorate the psychological state of the patients,
      and was found to be accepted more positively than feeding orally in the most
      critical initial phase, it should be included in the therapy.

PMID- 16639071
TI  - Percutaneous endoscopic gastrostomy placement without skin incision: results of a
      randomized trial.
AB  - BACKGROUND: During percutaneous endoscopic gastrostomy (PEG) placement, skin
      incision is performed as standard practice. We suspected that this time-honored
      principle is unnecessary. METHODS: In a prospective, randomized trial, 50 adults
      undergoing PEG placement were randomized to skin incision omission PEG (IOPEG)
      and standard PEG (SPEG). Two- and 7-day PEG site evaluations were performed to
      grade stomal infection, bleeding, pain, and overall satisfaction using a
      standardized scoring system. Median stomal evaluation scores were compared
      between groups using a Wilcoxon rank-sum test. Completion rates were compared
      using a t-test. RESULTS: Placement success for the IOPEG and SPEG technique was
      22/25 (88%) and 24/25 (96%), respectively (p = NS). Three failed IOPEG attempts
      required an incision to complete due to increased pull force encountered. One
      SPEG failed due to inability to transilluminate. Stomal evaluation scores of
      infection, bleeding, pain, leakage, and patient satisfaction were not
      significantly different at 2 or 7 days. No serious complications occurred as a
      result of skin incision omission. CONCLUSIONS: Omitting the skin incision does
      not significantly alter the placement success rate, patient satisfaction, or the
      rate of stomal complications, thus dispelling the dogma that a skin incision is
      mandatory for PEG placement and the myth that incisions reduce infectious
      complications.

PMID- 16639072
TI  - The use of a handheld calorimetry unit to estimate energy expenditure during
      different physiological conditions.
AB  - BACKGROUND: Accurately determining rates of energy expenditure (EE) under free
      living conditions is important in understanding the mechanisms involved in the
      development and prevention of obesity. Metabolic carts are not portable enough
      for most free-living situations. The purpose of this study was to compare a
      portable, handheld indirect calorimetry device (HealtheTech Incorporated, Golden,
      CO) to a metabolic cart (Physio-Dyne Instrument Corporation, Quogue, NY) during 3
      different physiologic states. METHODS: EE was measured by both the handheld
      calorimeter (5-10 minutes) and the metabolic cart (15-20 minutes) in 20 healthy
      subjects (18-35 years of age). Measurements were made during 3 physiologic
      states: (1) postabsorptive rest (REE), (2) postprandial rest (fed energy
      expenditure, FEE), and (3) while walking in place (activity energy expenditure,
      AEE). RESULTS: There were no significant differences between the means of the
      cart vs the hand-held device for REE (mean +/- SE; kcal/d; 1552 +/- 64 vs 1551 +/
      63), FEE (1875 +/- 99 vs 1825 +/- 86), and AEE (3333 +/- 218 vs 3489 +/- 152).
      The range over which the techniques were tested was 1300-5000 kcal/d. The
      agreement between the 2 methods was excellent for REE (0.80, p < .0001), FEE
      (0.89, p < .0001), and AEE (0.75, p < .0002). CONCLUSIONS: Compared with the
      metabolic cart, the handheld device provided similar estimates of energy
      expenditure during resting, postprandial, and physically active states. This
      suggests that portable indirect calorimetry devices can provide reliable and
      valuable information in free-living research situations for which maximal energy
      expenditure is <5000 kcal/d.

PMID- 16639073
TI  - Successful long-term jejunostomy feedings in relapsing pancreatitis: a case
      report.
AB  - Relapsing pancreatitis is characterized by repeated episodes of acute
      inflammation of the pancreas, with either a localized or a systemic organic
      response that may progress to chronic pancreatitis. Enteral jejunal feedings have
      been shown to be effective in the management of acute pancreatitis, but long-term
      use of jejunal feedings as treatment of relapsing pancreatitis has not been
      reported. We describe the case of a young patient treated with long-term jejunal
      feedings to induce remission and prevent recurrence of acute relapsing
      pancreatitis. An 18-year-old Hispanic man had well-documented recurrent episodes
      of acute pancreatitis. Multiple studies were performed as part of the diagnostic
      workup of the patient's relapsing pancreatitis, including endoscopic ultrasound,
      endoscopic retrograde cholangiopancreatography with biliary sphincterotomy, and
      laparoscopic cholecystectomy. Despite medical therapy, endoscopic and surgical
      procedures, the patient continued having episodes of pancreatitis on a monthly
      basis, with over 13 distinct documented episodes of pancreatitis during a 15
      month period. A jejunostomy tube was inserted surgically, and long-term jejunal
      feedings were instituted, with excellent control of the patient's symptoms. There
      was only 1 episode of pancreatitis in the ensuing 24 months associated with the
      resumption of oral feedings and a weight gain of 20 pounds during this time
      period. Chronic jejunal feedings seem to be an effective alternative for
      treatment and prevention of acute relapsing pancreatitis. To our knowledge, this
      is the first report of long-term enteral feedings in acute relapsing
      pancreatitis.

PMID- 16639074
TI  - Hyperglycemia during critical illness.
AB  - BACKGROUND: We sought to review the literature describing the benefits of tight
      glycemic control in critically ill patients, comparing outcome differences in
      subgroup populations. METHODS: We searched PubMed for relevant literature on the
      topic of hyperglycemia and its management in the intensive care unit. RESULTS:
      Overwhelming evidence in both surgical and medical patients conclusively
      demonstrates that hyperglycemia is a marker of severity of illness and is also an
      independent determinant of bad outcome, largely from infectious complications.
      Randomized trial evidence, in conjunction with historically controlled trials,
      supports the use of intensive insulin therapy and euglycemic control in
      critically ill patients, with nondiabetics possibly benefiting even more than
      diabetic patients. Euglycemia is best achieved, and hypoglycemia attenuated,
      through use of a protocolized approach. Further elaboration as to what threshold
      range defines euglycemia in patient subpopulations is needed and what pitfalls
      must be avoided in this practice. Development of continuous blood glucose
      monitoring has started and will someday be incorporated into routine practice in
      the same way that continuous electrocardiographic monitoring and pulse oximetry
      are standards of care in the intensive care unit. CONCLUSIONS: Hyperglycemia is a
      predictor of death and complications in critically ill patients. Early aggregated
      study results show that control of hyperglycemia improves outcomes. Well-designed
      studies involving thousands of patients have started to better elucidate the
      concomitant promoters of hyperglycemia and to better quantify the benefits from
      tight glycemic control.

PMID- 16639075
TI  - Parenteral nutrition safe practices: results of the 2003 American Society for
      Parenteral and Enteral Nutrition survey.
AB  - BACKGROUND: The American Society for Parenteral and Enteral Nutrition
      (A.S.P.E.N.) recently published a revision of its "Safe Practices for Parenteral
      Nutrition" guidelines. Because there is a paucity of published scientific
      evidence to support good practices related to ordering, compounding, and
      administering parenteral nutrition (PN), a survey was performed in the process of
      the revision to gain insight into the discrepancies between reported practices
      and previous guidelines. METHODS: A web-based survey consisting of 45 questions
      was conducted (n = 651) June 1-30, 2003. Respondents were queried about primary
      practice setting, professional background, processes for writing PN orders,
      computer order entry of PN orders, problems with PN orders, and adverse events
      related to PN. RESULTS: There were 651 survey responses, 90% of which were from
      hospital-based practitioners. Almost 75% of responders processed between 0 and 20
      PN orders per day. Overall, physicians (78%) were responsible for writing PN
      orders, but dietitians and pharmacists had significant involvement. PN base
      components were most often ordered as percentage final concentration after
      admixture (eg, 20% dextrose), which is inconsistent with safe practice guidelines
      of ordering by total amount per day (eg, 200 g/day). There was no consistent
      method for ordering PN electrolytes. Approximately 45% of responders reported
      adverse events directly related to PN that required intervention. Of these
      events, 25% caused temporary or permanent harm, and 4.8% resulted in a near-death
      event or death. CONCLUSIONS: Although the survey found consistency in PN
      practices for many areas queried, significant variation exists in the manner by
      which PN is ordered and labeled.

PMID- 16639076
TI  - The vulnerability of biomedical science.

PMID- 16639077
TI  - The role of lipolysis in mediating the proinflammatory effects of very low
      density lipoproteins in mouse peritoneal macrophages.
AB  - Hypertriglyceridemia is an important risk factor for atherosclerosis, especially
      in obesity. Macrophages are one of the primary cell types involved in
      atherogenesis and are thought to contribute to lesion formation through both
      lipid accumulation and proinflammatory gene expression. In this study, we sought
      to determine the direct impact of triglyceride (TG)-rich VLDL-induced lipid
      accumulation on macrophage proinflammatory processes. Incubation of mouse
      peritoneal macrophages with 100 microg/ml VLDL for 6 h led to 2.8- and 3.7-fold
      increases in intracellular TGs and FFAs, respectively (P < 0.05). The
      inflammatory proteins tumor necrosis factor-alpha, interleukin-1beta, monocyte
      chemoattractant protein-1, intercellular adhesion molecule-1, matrix
      metalloproteinase 3 (MMP3), and macrophage inflammatory protein-1alpha (MIP
      1alpha) were all upregulated by at least 2-fold (P < 0.05) in a dose-dependent
      manner in VLDL-treated macrophages. The increase in inflammatory gene expression
      coincided with the phosphorylation of the mitogen-activated protein kinase (MAPK)
      pathway members extracellular signal-regulated kinase (ERK) 1/2, stress-activated
      protein kinase/c-Jun NH2-terminal kinase, and p38 MAPK and was ameliorated by
      U0126, an inhibitor of ERK1/2. Inhibition of extracellular TG hydrolysis with
      tetrahydrolipstatin (Orlistat) resulted in the absence of intracellular TG and
      FFA accumulation and was accompanied by the amelioration of ERK1/2
      phosphorylation and MIP-1alpha gene expression. These data indicate that VLDL
      hydrolysis, and the subsequent accumulation of intracellular FFAs and TGs, plays
      a substantive role in mediating the proinflammatory effects of VLDL. These data
      have important implications for the direct proatherogenic effects of VLDL on
      macrophage-driven atherosclerosis.

PMID- 16639078
TI  - Transgenic mice express human MPO -463G/A alleles at atherosclerotic lesions,
      developing hyperlipidemia and obesity in -463G males.
AB  - Myeloperoxidase (MPO) is an oxidant-generating enzyme present in macrophages at
      atherosclerotic lesions and implicated in coronary artery disease (CAD). Although
      mouse models are important for investigating the role of MPO in atherosclerosis,
      neither mouse MPO nor its oxidation products are detected in lesions in murine
      models. To circumvent this problem, we generated transgenic mice expressing two
      functionally different human MPO alleles, with either G or A at position -463,
      and crossed these to the LDL receptor-deficient (LDLR(-/-)) mouse. The -463G
      allele is linked to higher MPO expression and increased CAD incidence in humans.
      Both MPO alleles were expressed in a subset of lesions in high-fat-fed LDLR(-/-)
      mice, notably at necrotic lesions with cholesterol clefts. MPOG-expressing LDLR(
      /-) males (but not females) developed significantly higher serum cholesterol,
      triglycerides, and glucose, all correlating with increased weight gain/obesity,
      implicating MPO in lipid homeostasis. The MPOG- and MPOA-expressing LDLR(-/-)
      males also exhibited significantly larger aortic lesions than control LDLR(-/-)
      males. The human MPO transgenic model will facilitate studies of MPO involvement
      in atherosclerosis and lipid homeostasis.

PMID- 16639079
TI  - Liquid chromatography-mass spectrometry for comprehensive profiling of ceramide
      molecules in human hair.
AB  - Ceramides (CERs) play key roles in signal transduction and cell regulation,
      probably during the keratinization of human hair. Current methods using mass
      spectrometry (MS), however, are not sufficient to allow the comprehensive
      analysis of CER molecules, including isobaric and isomeric CERs. Therefore, a
      method for the comprehensive profiling of CERs was developed. The method
      developed is based on reversed-phase liquid chromatography (RPLC) coupled to
      atmospheric pressure chemical ionization (APCI)-MS. Comprehensive identification
      and profiling of CERs is achieved using two sets of multimass chromatograms
      obtained from two channel detections that monitor both molecular-related and
      sphingoid-related ions under two different in-source collision-induced
      dissociation conditions and using retention times obtained from RPLC. The
      application of this method revealed that human hair contains 73 species of CER
      molecules, which were all corroborated by structural analysis using tandem mass
      spectrometry. The results further revealed that the composition is characterized
      by predominant molecules consisting of even carbon atom-containing
      saturated/unsaturated nonhydroxy or alpha-hydroxy fatty acids and C(18)
      dihydrosphingosine, a minor but distinct content of isobaric/isomeric and odd
      chain-containing CERs. This successfully developed RPLC-APCI-MS technique allows
      the comprehensive profiling of CER molecules in hair for the investigation of
      their physicochemical and physiological roles.

PMID- 16639080
TI  - BRCA1 downregulation leads to premature inactivation of spindle checkpoint and
      confers paclitaxel resistance.
AB  - BRCA1 germline mutations predispose women to early onset, familial breast and
      ovarian cancer. BRCA1 has been recently implicated in the cellular response to
      agents that disrupt the mitotic spindle. In this report, we studied BRCA1
      contribution to paclitaxel response in MCF-7 breast cancer cells. We show that
      MCF-7 cells transfected with BRCA1 siRNA display a significant increase in
      resistance to paclitaxel compared with the control cells. We next demonstrate
      that downregulation of BRCA1 reduces the mitotic index and triggers premature
      cyclin B1 degradation and decrease in Cdk1 activity following paclitaxel
      treatment, suggesting that BRCA1 downregulation results in precocious
      inactivation of the spindle checkpoint. These findings were confirmed by showing
      that BRCA1 downregulation induces premature sister-chromatids separation in MCF-7
      cells following spindle damage. Furthermore, we show that BRCA1 up-regulates the
      expression of the protein kinase BubR1, essential component of the functional
      spindle checkpoint, whose downregulation is known to result in paclitaxel
      resistance in MCF-7 cells. Altogether, our findings support the notion that
      downregulation of BRCA1 expression mediates paclitaxel resistance through
      premature inactivation of spindle checkpoint in MCF-7 breast cancer cells. They
      link BRCA1 to the mitotic checkpoint that plays an essential role in the
      maintenance of chromosomal stability.

PMID- 16639081
TI  - Micro or mega: how important are microRNAs in muscle?

PMID- 16639083
TI  - Nutrition and geriatric psychiatry: a neglected field.
AB  - PURPOSE OF REVIEW: Nutritional issues have received little attention in geriatric
      psychiatry research. This review focuses on literature published in 2003 and 2004
      on nutritional factors in mental illness in the elderly and proposes directions
      for future research. RECENT FINDINGS: There has been more research on the role of
      micronutrients in psychiatric disorders of older adults but studies examining
      nutritional state in this population are lacking. The former research suggests
      associations between low folic acid/vitamin B12 status and depression in older
      adults whereas evidence for other micronutrients is still tentative. In the
      latter work, there is only one study that examines malnutrition in
      psychogeriatric patients despite the availability of well-validated screening
      tools for assessing nutritional state in the elderly and the known impact of
      undernutrition in ageing and the development of frailty. The role of obesity in
      ageing is also relevant especially as more people with schizophrenia live longer,
      although the current evidence in the non-mentally ill elderly suggests that being
      overweight may have protective effects in the elderly. SUMMARY: Malnutrition is
      likely to have considerable impact on the mental and physical state of the
      elderly.

PMID- 16639084
TI  - 'Alzheimer's disease': more data, but are we any more informed?
AB  - PURPOSE OF REVIEW: While we adhere to traditional misconceptions regarding the
      nature of age-associated neurodegenerative, and vascular and other brain changes,
      we will not re-design our research projects, and we will not reconsider and
      improve our pragmatic diagnostic and therapeutic approach. RECENT FINDINGS: This
      review focuses (1) on the continuum of cognitive deficits from mild cognitive
      impairment to manifest dementia, (2) on the spectrum of neurodegenerative,
      vascular and other cerebral co-morbidity, and (3) on some reversible examples of
      the rare outliers (limbic encephalitis, Hashimoto encephalopathy) not to be
      included in the common severity and cerebral co-morbidity spectrum of senile
      cognitive impairment. SUMMARY: We will only be more informed if we accept
      appropriate concepts and draw the right conclusions. Important new research has
      not yet filtered into the minds of dementia researchers specializing in 'normal
      ageing' or 'mild cognitive impairment', 'Alzheimer's disease' or 'dementia with
      Lewy bodies', tauopathies or synucleopathies, etc.

PMID- 16639085
TI  - Neuropsychology in Alzheimer's disease and other dementia research.
AB  - PURPOSE OF REVIEW: This review describes a variety of neuropsychological dementia
      studies published between January 2004 and June 2005. In selecting articles for
      description in the present paper, our goal was not a comprehensive review of what
      is an enormous and growing literature, but rather to select and describe
      individual interesting studies from a sufficient range of dementia-related topics
      to permit illustration of some of the important questions for which a
      neuropsychological perspective aids in the understanding of dementias. RECENT
      FINDINGS: Findings in the studies reviewed include a variety of different topics.
      Some of the themes include the following: (a) Alzheimer's disease is the most
      common cause of dementia, but a large body of research documents that there are
      important cognitive differences among various types of dementia, (b) the emerging
      research is also important in demonstrating the need for more sensitive clinical
      screening measures, (c) cognitive data are strongly predictive of functional
      decline, and (d) subtle declines in verbal learning appear to precede clinical
      Alzheimer's disease. SUMMARY: Neuropsychological data are key to progress in
      understanding and developing more effective treatments for Alzheimer's disease
      and other dementia. For instance, efforts to identify early markers of dementia
      will be a key component to development of early intervention strategies.

PMID- 16639086
TI  - Telling the difference between frontotemporal dementia and Alzheimer's disease.
AB  - PURPOSE OF REVIEW: A precise diagnosis of the cause of dementia during life is
      needed for proper management, in order to explain the symptoms to the patient and
      to the close relatives, and to give appropriate indications on the prognosis and
      possibly on the genetic risk. Frontotemporal dementia remains under-diagnosed and
      often misdiagnosed for Alzheimer's disease, the most common cause of dementia.
      More and more studies explore the differences between the two syndromes. RECENT
      FINDINGS: Progress in neuropsychological testing improves the ability to
      distinguish between syndromes and knowledge on brain functioning. More attention
      has been paid over these last months--or years--on emotion, insight, behavior,
      artistic creativity and quality of responses. Yet, biomarkers do not improve the
      diagnostic accuracy of trained clinicians, and do not help to distinguish between
      histological subtypes of frontotemporal dementia. SUMMARY: Improvement in
      knowledge on cognitive and emotional impairment in frontotemporal dementia and
      Alzheimer's disease is essential for the management of the patient--information
      can be given to the patients and the families that helps them to understand and
      to behave in consequence.

PMID- 16639087
TI  - Taking care of the caregivers.
AB  - PURPOSE OF REVIEW: Comprehensive treatment for people with chronic illnesses or
      disabilities should include interventions for their family caregivers. In order
      for such interventions to achieve widespread implementation, they must first be
      proven efficacious in randomized controlled trials. The present review briefly
      summarizes the recent literature on the results of randomized controlled trials
      and pilot studies of psychosocial interventions for caregivers. RECENT FINDINGS:
      Many of the recent studies of psychosocial interventions for caregivers have
      resulted in significant outcomes, regardless of the chronic illness of the
      relative or friend for whom care is being provided. While didactic interventions
      can provide knowledge, supportive interventions generally have more impact on
      caregiver and patient emotional and psychological well-being. Pilot studies
      suggest that new modes of intervention, such as telephone-based and web-based
      counseling and support, show promise and appear to be feasible. Psychosocial
      interventions for caregivers that are individualized and flexible, and provide
      long-term support appear to be the most efficacious. SUMMARY: The literature on
      caregiver intervention studies, conducted in research centers, suggests that
      treating the caregiver may be an important component of a comprehensive treatment
      for chronic diseases and disabilities. Interventions with demonstrated efficacy
      should now be tested more widely in community settings in multiple geographic
      settings, ethnic groups, disease entities and caregiver types, to more fully
      evaluate their generalizability and effectiveness.

PMID- 16639088
TI  - Imaging in neurodegenerative disorders: recent studies.
AB  - PURPOSE OF REVIEW: Advances in neuroimaging have expanded its already central
      role in neurodegenerative disorders. RECENT FINDINGS: The main advances we
      emphasize are imaging of amyloid in Alzheimer's disease, serial co-registered
      magnetic resonance imaging in frontotemporal lobar degeneration and imaging of
      nigrostriatal dysfunction in dementia with Lewy bodies. SUMMARY: All of these
      techniques offer ways of improving diagnosis.

PMID- 16639089
TI  - Who are we and what are we doing here?

PMID- 16639090
TI  - Psychiatry, philosophy and the self.
AB  - PURPOSE OF REVIEW: The aim of this article is to investigate psychopathology in
      order to illuminate the nature of personal identity. RECENT FINDINGS:
      Predominantly, the authors reviewed here defend a more robust version of the
      narrative self against Dennett's claim that narrative self is ultimately a useful
      fiction. Authors explore the limit case of dissociative identity disorder in
      order to explore how apt an embodied, socially interactive and autonomous
      narrative self is for addressing legal and moral paradoxes intertwined with
      establishing personal identity. SUMMARY: Psychiatric practice should embrace
      therapeutic approaches that restore the unity inherent to the capacity to narrate
      a life.

PMID- 16639091
TI  - Boundaries of mental disorders.
AB  - PURPOSE OF REVIEW: This article reviews the problem of 'boundaries' in
      psychopathology and its conceptualization in the diagnostic classification of
      psychiatric disorders. RECENT FINDINGS: A modest number of publications in 2004
      2005 contribute concepts, methods and data relevant to several aspects of the
      problem: scientific 'facts' versus value attribution in the definition of mental
      disorders; the problem of comorbidity between diagnostic entities; the spurious
      dichotomy between categorical versus dimensional approaches to diagnosis and
      classification; and the distinction between validity and pragmatic utility.
      SUMMARY: The relative paucity of research explicitly addressing these issues
      should be a reason for concern in the debate leading up to the next revisions of
      the International Classification of Diseases and the Diagnostic and Statistical
      Manual of Mental Disorders.

PMID- 16639092
TI  - Philosophy of psychopathology.
AB  - PURPOSE OF REVIEW: Psychiatry is increasingly aware of its own conceptual
      foundations and the role that philosophy plays in shaping research and practice.
      This growing awareness is especially prominent in the area of psychopathology,
      where both philosophers and psychiatrists are actively investigating the basic
      assumptions and values that influence the science. RECENT FINDINGS: There is
      growing attention to the role of values in understanding both the concepts of
      psychopathology, and the philosophical assumptions that underlie research
      strategies for studying it. Provocative work is being done to clarify the concept
      of 'mental disorder', to identify the influence of values in the classification
      and diagnosis of psychopathology, and to use values to argue for comprehensive
      research efforts. Psychometricians increasingly question the interplay between
      the philosophical theory and empirical study of psychopathology. SUMMARY: Both
      epistemology and value theory are central to the conceptualization and research
      of psychopathology. This prominence is recognized not only by philosophers and
      psychiatrists interested in philosophy, but by investigators who must grapple
      with the mutual influence of philosophical concepts and research methods. By
      making our philosophical views explicit and maintaining our awareness of them, we
      are well poised to develop and question both our philosophical and our research
      methods in meaningful ways.

PMID- 16639093
TI  - Concepts of recovery: competing or complementary?
AB  - PURPOSE OF REVIEW: Within the last 5 years, concepts of recovery have taken
      center stage in psychiatry as the overarching goal of mental health services. In
      the course of this shift towards recovery, clinicians and consumers (and many
      others) have struggled to make the concept of recovery both measurable and
      meaningful. The clinical concept of recovery has focused upon the remission of
      symptoms and restoration of functioning. A rehabilitation model of recovery has
      been a more subjective and consumer-oriented concept that focuses on the full
      lives that are lived within the context of enduring disability. RECENT FINDINGS:
      A review of the literature addressing the concepts of recovery over the last 2
      years demonstrates that authors are rarely explicit about the perspective of
      recovery from which they are writing. Almost all of the representative papers,
      however, struggled with how best to define, measure and validate recovery in its
      broadest terms. Several authors reviewed the history of recovery and offered
      conceptual discussions of either their first-person experiences or implications
      for mental health practice. Other authors, regardless of their perspective on
      recovery, sought to more concretely define criteria for recovery, for the
      purposes of recovery measure development or more rigorous research of the
      concept. SUMMARY: As authors struggle to reconcile these often competing concepts
      of recovery, we suggest that both concepts are useful for different purposes and
      populations and that the synthesis of the two will offer a broader perspective on
      life with, after, or despite mental illness.

PMID- 16639094
TI  - Psychiatrists' biographies.
AB  - PURPOSE OF REVIEW: This review focuses on publications dealing with
      psychiatrists' biographies. RECENT FINDINGS: Compared with scientific mainstream
      topics in psychiatry, the present area constitutes a small but nonetheless highly
      heterogeneous field. The selected papers are categorized with regard to what
      relevance is given to biographical data in a narrow sense or to conceptual issues
      for which the biography of a certain author functions as an illustration. Mere
      hagiographic biographical notes were not taken into consideration, and nor were
      plain polemics. Although the differentiation mentioned above seems useful in
      order to get an overview, it is de facto not possible to clearly separate
      biographical from conceptual aspects. This may be true for all fields in the
      history of science, but it is definitely true in the history of psychiatry with
      its numerous long-standing theoretical controversies - many of them still
      unresolved and all of them closely linked with the lives of their prominent
      representatives. SUMMARY: The biographical approach can be helpful in proving
      that research on the history of psychiatry--if done beyond mere hagiography or
      simple polemic--is of crucial importance for the understanding and development of
      theoretical and practical issues in our field.

PMID- 16639095
TI  - Hand-offs and trade-offs in psychiatric care.

PMID- 16639096
TI  - Post-hospitalization transitional care needs of depressed elderly patients:
      models for improvement.
AB  - PURPOSE OF REVIEW: In the weeks immediately following psychiatric hospital
      discharge, severely depressed elderly patients are at risk of 'falling through
      the cracks' in a complex health care system: becoming lost to follow-up,
      receiving inadequate care, or requiring prompt readmission. The purpose of this
      review is to highlight recent literature on the comorbid physical health problems
      and complex care needs of elderly patients hospitalized for depression. This
      paper will also review recent initiatives to improve the quality of care
      transitions for elderly patients discharged from medical hospitals that may be
      adaptable to a severely depressed population. RECENT FINDINGS: Due to shorter
      hospital stays, comorbid physical health problems, and limitations in functional
      capacity, severely depressed elderly patients discharged from psychiatric
      hospitals have complex service needs, and numerous barriers to care, immediately
      following hospital discharge. There is a lack of research specifically addressing
      the transitional care needs of this population. Improvement interventions
      assigning transitional care providers to chronically medically ill elderly
      patients immediately after medical hospital discharge have shown decreased rates
      of rehospitalization and emergency services utilization, and appear to be cost
      effective. SUMMARY: Further research is needed to adapt successful transitional
      care interventions targeting chronically ill elderly patients in medical
      hospitals to severely depressed elderly patients being discharged from
      psychiatric hospitals.

PMID- 16639097
TI  - New psychiatric and psychological aspects of diagnosis and treatment of hepatitis
      C and relevance for opiate dependence.
AB  - PURPOSE OF REVIEW: This review highlights the aspects of the hepatitis C virus
      that are important to the psychiatrist. RECENT FINDINGS: Hepatitis C virus
      infection is frequently associated with mental clouding, depression,
      neurocognitive impairment, and deterioration in the quality of life. In recent
      studies psychiatric symptoms have been linked to psychiatric comorbidity rather
      than to direct hepatitis C virus neurotoxicity. Infection of the central nervous
      system, however, is thought to play a role at least in hepatitis C virus
      associated neurocognitive deficits. Application of the anti-hepatitis C virus
      agent interferon-alpha is regularly accompanied by psychiatric symptoms, most
      often depression. Antidepressant treatment may support interferon therapy, but
      its general indication and timing remain debatable. The problem of hepatitis C
      virus treatment in manic patients is still unsolved. Hepatitis C infection rates
      in injection drug users are often 90% and higher, while these patients in
      particular face barriers when trying to access treatment. Recent studies
      demonstrated feasibility of hepatitis C virus treatment in injection drug users
      in specialized treatment settings. SUMMARY: Hepatitis C virus infection is
      associated with psychiatric comorbidity and injection drug use, while treatment
      of the virus is frequently accompanied by neuropsychiatric symptoms.
      Psychiatrists are particularly qualified to support diagnosis of hepatitis C
      associated comorbidity and to render treatment feasible. Evaluation of treatment
      options and settings in infected patients with psychiatric comorbidity or
      injection drug users is required, as well as investigation of association of
      hepatitis C virus infection, and psychiatric and neurocognitive symptoms in
      properly defined samples.

PMID- 16639098
TI  - Caregiver burden in mental illness: review of measurement, findings and
      interventions in 2004-2005.
AB  - PURPOSE OF REVIEW: This review summarizes recent evidence on caregiver burden in
      mental illness. It examines how the field has advanced in terms of measurement,
      results, and interventions in 2004/2005, and identifies potential for further
      studies. RECENT FINDINGS: Burden has been studied in a much wider spectrum of
      diagnostic groups and types of caregivers, some brief and practical assessment
      tools have become available, cultural aspects of burden are better understood,
      and a high potential for caregiver appraisal to prevent negative consequences of
      burden has been identified. Recent findings afford a more comprehensive
      understanding of the caregiving situation and its outcomes, and may find a
      practical application in devising effective support strategies for family carers,
      which still seem to be lacking. SUMMARY: Substantial progress has been made in
      the measurement of caregiver burden. In terms of publication quantity, the field
      is growing rapidly, and international interest in the area is increasing.
      Improvements in methodological quality are also evident. These new research
      developments may be taken to reflect an increasing recognition of the
      contribution of families-away from stigma, shame, and blame. This requires
      accepting relatives as caregiving experts and as genuine partners in both
      psychiatric practice and research.

PMID- 16639099
TI  - Clinical trial design in schizophrenia: implications for clinical decisions.
AB  - PURPOSE OF REVIEW: Results from clinical trials do not necessarily provide
      information for decisions in clinical practice. This review aims to present
      strengths and limitations of different methodological types of clinical trials
      and to offer an overview of how knowledge from clinical trails can be distilled
      for clinical practice. Selected key questions in the treatment of schizophrenia
      are presented, with a focus on the possibilities and restrictions of translating
      trial results into real-world practice. RECENT FINDINGS: Randomized controlled
      trials are the gold standard for proving efficacy of a diagnostic or therapeutic
      procedure. They have a high degree of internal validity and a clear-cut message
      when conducted to good-quality standards but suffer from a lack of
      generalizability (external validity). Effectiveness studies evaluate effects of
      treatments under conditions approximating usual care. They may include patient
      centred outcomes or health economic evaluations. According to the type of trial,
      specific problems arise in the interpretation of results. Typical examples are
      given for the treatment of acute exacerbations of schizophrenia, for relapse
      prevention and for the treatment of cognitive impairment. SUMMARY: Clinical
      decisions have to be made upon the best knowledge. Therefore, well conducted
      studies addressing all major issues from all relevant perspectives are needed.
      The assessment of a treatment regimen for clinical utility requires both efficacy
      and effectiveness studies. An understanding of the design, analysis and
      conventions of both study types is essential for the interpretation of results
      and their translation to the clinical decision-making process.

PMID- 16639100
TI  - Bibliography. Current world literature. Geriatric psychiatry.

PMID- 16639102
TI  - Widening the lens on intellectual disabilities: an emerging focus on genetics,
      the lifespan and evidence-based practice.

PMID- 16639103
TI  - Evidence-based practices in intellectual disability and behaviour disorders.
AB  - PURPOSE OF REVIEW: To critically review the most recently published studies on
      the treatment of challenging behaviours/behaviour disorders for individuals with
      intellectual disability. RECENT FINDINGS: Literature published in the review
      period was from three traditions: applied behaviour analysis, psychopharmacology,
      and service evaluation. Applied behaviour analysis treatments have a large
      evidence base, and recent research has focused on refining issues such as dealing
      with low rate behaviours, improving generalization, the effects of choice-making,
      and setting event variables that may affect treatment outcomes. Recent interest
      in risperidone as a treatment for behaviour disorder has dominated the literature
      on pharmacological interventions. Several empirical studies support the use of
      risperidone in children, although a recent review is more sceptical of the
      quality of the evidence to date. A small number of service evaluation studies
      suggest in particular that applied behaviour analysis technologies can be scaled
      up to benefit large numbers of patients. SUMMARY: Applied behaviour analysis
      methods for the assessment and treatment of behaviour disorders continue to be
      the focus of research, and continue to result in positive outcomes. Recent data
      show the value of using applied behaviour analysis technologies as a service
      model for people with behaviour disorders. Pharmacological treatments, especially
      risperidone, also have a developing evidence base despite a lack of understanding
      of their mechanisms of action. A number of questions about behaviour disorders
      remain unanswered, especially whether early intervention may be effective and
      their putative relationship with psychiatric conditions.

PMID- 16639104
TI  - Assessment in intellectual disability.
AB  - PURPOSE OF REVIEW: This review examines an eclectic selection of publications
      from the past 12 months under the broad heading of 'assessment in intellectual
      disability'. Being unable to cover all possible publications the authors have
      concentrated on the assessment of pain (in those with severe intellectual
      disability), psychopathology, risk assessment and offending, autism, preference
      and choice, and dementia. RECENT FINDINGS: Research into assessment has generally
      taken the form of developing new instruments, or adapting existing ones, or
      comparing the performance of a range of scales in a certain area. Researchers are
      using increasingly sophisticated psychometric analyses and refining the nature
      and purpose of tools for a range of clinical purposes. SUMMARY: The result of
      recent effort in this area is better instruments, often developed by experienced
      researchers who have been working in their chosen area of speciality for some
      years. It has been a very worthwhile period of extension and consolidation.

PMID- 16639105
TI  - Self-injurious behaviour in individuals with intellectual disabilities.
AB  - PURPOSE OF REVIEW: In this paper we review literature published in 2004 on self
      injurious behaviour in individuals with intellectual disabilities. Reviewed
      studies examine phenomenology and comorbidity, pharmacological and other
      interventions, genetic syndromes, and behavioural assessment and treatment.
      RECENT FINDINGS: Key findings include the possible association between self
      injury and impulse control and stereotyped behaviours. Reports on the use of
      pharmacological interventions provide little evidence for the use such
      interventions, although the findings of studies on naltrexone seem stronger. In
      the behavioural phenotype literature the predictors of self-injury in Prader
      Willi syndrome are becoming more refined. The behaviour analysis literature
      reports further development of assessment methodology to cater for idiosyncratic
      functions and low-rate behaviours. SUMMARY: Developments in the fields of applied
      behaviour analysis and genetic syndromes highlight the importance of tailored
      assessments and interventions. Evidence from the pharmacological literature
      suggests that although significant numbers of individuals are prescribed such
      interventions, the research evidence for their efficacy is, at best, weak.

PMID- 16639106
TI  - Recent advances in fragile X: a model for autism and neurodegeneration.
AB  - PURPOSE OF REVIEW: This review will describe recent developments in the
      neurobiology of fragile X syndrome (FXS), the association between FXS and autism,
      and involvement in premutation carriers. RECENT FINDINGS: Metabotropic glutamate
      receptor 5 (mGluR5)-coupled pathways are dysregulated in individuals with FXS and
      this is thought to relate to the FXS phenotype. The mGluR5 model suggests that
      mGluR5 antagonists, including downstream effectors such as lithium, could be
      useful for treating FXS. Two forms of clinical involvement associated with the
      fragile X mental retardation 1 (FMR1) gene, autism and fragile X-associated
      tremor/ataxia syndrome (FXTAS), have received additional attention during the
      past year. One study has found that approximately 30% of individuals with FXS
      have autism; those with autism have lowered cognitive abilities, language
      problems, and behavioral difficulties compared to those with FXS alone.
      Furthermore, evidence is mounting that autism also occurs in some young males who
      have premutation alleles. Finally, males and occasional females with premutation
      alleles may develop a neurological syndrome with aging that consists of tremor,
      ataxia, peripheral neuropathy, and cognitive deficits. Significant brain atrophy
      and white-matter disease is usually seen. This new disorder (FXTAS) is thought to
      be related to elevated levels of abnormal FMR1 mRNA. SUMMARY: Full-mutation forms
      of the gene (> 200 repeats) can cause autism, learning disabilities, anxiety
      disorders, and mental retardation. Disorders associated with premutation forms of
      the gene (55-200 repeats) include, in addition to autism, FXTAS in older males
      and females, and premature ovarian failure.

PMID- 16639107
TI  - Current trends in psychological research on children with high-functioning autism
      and Asperger disorder.
AB  - PURPOSE OF REVIEW: This review explores current trends in the literature during
      2004 on psychological studies of children with high-functioning autism and
      Asperger syndrome. Studies are reviewed that examine diagnostic dilemmas and
      methodological concerns, cognitive and social deficits, and interventions. RECENT
      FINDINGS: There is considerable debate over the distinction between high
      functioning autism and Asperger syndrome, but few studies find support for
      separate disorders. Most studies reviewed combine high-functioning autism and
      Asperger syndrome into an autism spectrum disorder group or study only one
      diagnostic group, either high-functioning autism or Asperger syndrome. Research
      into cognitive processes (specifically mentalizing) and social understanding
      (nonliteral language) continue to dominate research efforts. Current studies
      suggest specific weaknesses in many areas of nonliteral language, such as humor,
      irony, and teasing. Studies rely heavily on current theoretical explanations for
      deficits, namely the central coherence, social inference, and executive function
      theories, and varying levels of support were found for all three theories.
      Intervention and outcome studies lag behind experimental and theoretical studies,
      but two studies employed scientifically rigorous intervention designs with
      promising results. SUMMARY: Children with high-functioning autism and Asperger
      syndrome have a great deal of potential with respect to long-term developmental
      outcomes, and yet they continue to be understudied and under-served in current
      intervention programs. Future studies are needed in developmental processes and
      outcomes in this population, and in the development of effective treatment
      strategies that have undergone scientifically rigorous testing.

PMID- 16639108
TI  - Ageing and health issues in intellectual disabilities.
AB  - PURPOSE OF REVIEW: This review summarizes recent research and evidence-based
      practice and policy guidelines from 31 articles or books focused on the health of
      ageing individuals with intellectual disabilities. RECENT FINDINGS: Findings are
      presented under four headings that correspond to categories of health measures
      applied in recent EU evidence-based public health documents. Large group studies,
      notably longitudinal studies, have advanced knowledge of the health-related
      attributes of the population of older adults with intellectual disabilities and
      their distinctive health risks, including those linked to aetiologies. Empirical
      studies applying various research designs and literature reviews presented
      findings about weight and levels of physical activity, prevalent health problems
      (e.g. high levels of sensory impairment, risk factors for coronary artery
      disease) and other aspects of the health status of this population. Efforts to
      improve assessment methods for dementia continue. Evidence from small group
      studies in Israel and the USA suggests that interventions to increase physical
      activity and functioning of older adults may be beneficial. Pharmacological
      studies consider treatments for dementia as well as widespread prescription of
      medications to manage challenging behaviours. Health system issues include access
      to health care, training for health professionals, support for family care
      givers, end of life care and more cohesive national health policies. SUMMARY:
      Health-related research in older people with intellectual disabilities has
      extended our understanding of the characteristics of this population relative to
      other groups of older individuals and to national populations in terms of health
      status, determinants of health and priorities for policy and practice.

PMID- 16639109
TI  - Families and intellectual disability.
AB  - PURPOSE OF REVIEW: This review includes recent research pertaining to family
      functioning when there is a child or adult offspring with intellectual
      disability. The purpose was to broaden the examination of families research from
      an adjustment/coping perspective to consideration of more contextual factors
      (environment, culture, service delivery). RECENT FINDINGS: Studies continue to
      focus on parental well being, with parents of children with intellectual
      disability still showing evidence of stress and depression. Increasing evidence
      is accruing, however, that child behavior problems or specific syndrome more
      directly relate to poorer parental well being. On the other hand, parenting
      behaviors also contribute to child behaviors, with studies highlighting the
      importance of parenting context and dynamics. Interventions focus on child
      behaviors as well as on stress reduction for parents. Finally, the continued
      involvement of parents across the lifespan of their young adult with intellectual
      disability is apparent from studies of quality of life and living arrangements.
      SUMMARY: The well being of family members continues to be an area of interest,
      with special emphasis on siblings and cultural context. Methodological rigor in
      families research also continues to increase, with diverse methodologies
      represented. There is still a need, however, for the development of theoretical
      models within which to frame future research on topics such as siblings, as well
      as both negative and positive impact on families.

PMID- 16639110
TI  - The ethics of biomedical research on prisoners.

PMID- 16639111
TI  - Ethical issues in the use of genetic information in the workplace: a review of
      recent developments.
AB  - PURPOSE OF REVIEW: In the wake of the Human Genome Project, the pace of genetic
      discovery has quickened. New genetic tests and other molecular technology have
      had immediate and wide relevance to American and European workers. These tests
      have the potential to provide improved workplace safety and protect workers'
      health, but they also carry the risk of genetic discrimination including loss of
      employment, promotion, insurance and health care. Ethical safeguards are
      necessary if the benefits are to outweigh the adverse consequences of genetics in
      the workplace. RECENT FINDINGS: This review examines the major policy statements
      issued in Europe and the USA from 2000 to 2005 pertaining to genetic issues in
      occupational health. Recent findings stress that genetic testing can only be
      utilized with worker consent and that the workers should control access to
      genetic information. Such testing is only justified when the information is
      required to protect the safety of the worker or a third party. The progress of
      occupational genetic technology should not be permitted to shift the
      responsibility for a safe working environment from the employer to the employee.
      Genetic discrimination in all forms is neither supported scientifically nor
      warranted ethically. SUMMARY: Increasingly, occupational physicians and
      clinicians treating workers will be faced with potentially stigmatizing genetic
      information and there is an urgent need for education and research to expand and
      implement the recommendations of major governmental and professional policy
      statements.

PMID- 16639112
TI  - Prisons and the human rights of persons with mental disorders.
AB  - PURPOSE OF REVIEW: This paper deals with issues of human rights related to
      persons suffering from a mental disorder in the prison system. In particular, I
      consider whether the rights afforded prisoners with mental disorders in various
      international conventions and resolutions are being implemented in legislation
      and case law. RECENT FINDINGS: There have been advances in recent years in the
      Western world, particularly in the USA and the UK, with regard to prisoners'
      rights. In the UK, there is now a partnership of responsibility between the
      National Health Service and the Prison Service so that these organizations would
      become jointly responsible for delivering health care to prisoners. In the USA,
      the Prison Rape Elimination Act of 2003 and the Mentally Ill Offender Treatment
      and Crime Reduction Act of 2004 go a long way in ensuring the basic rights of the
      imprisoned individual. SUMMARY: The large number of mentally ill inmates
      necessitates a continuous safeguarding of the rights of these individuals. It is
      now widely acknowledged that prisoners should be entitled to expect the same
      standard of health care as that provided to persons with unrestricted freedom,
      and have similar access to psychiatric beds. Further research is needed to see
      whether the improvement in their rights also improves their mental health and the
      long-term outcome of their illness.

PMID- 16639113
TI  - HIV-related issues and concerns for imprisoned persons throughout the world.
AB  - PURPOSE OF REVIEW: To summarize articles related to HIV/AIDS and correctional
      populations that were published from January 2004 through March 2005. In all, 43
      empirical and seven non-empirical articles are summarized, about two-thirds of
      which are focused on correctional populations in the USA. The majority of the
      studies were descriptive; only two articles presented evaluation data for HIV
      prevention interventions. RECENT FINDINGS: Published studies during the review
      period documented elevated rates of HIV, STIs, and hepatitis among correctional
      populations--often associated with injection drug use, mental illness, and
      infectious-disease co-morbidity. These studies highlighted a global public-health
      need for comprehensive HIV risk-reduction programs that address not only disease
      prevention but also the factors enabling disease transmission. Research further
      demonstrated the detrimental effects of release from prison on medication
      adherence and disease progression among HIV-positive people, underscoring the
      need for transitional treatment and health-care services. SUMMARY: HIV-related
      research is urgently needed to document the global scope of HIV disease
      prevalence and correlates among incarcerated populations, to examine the impact
      of incarceration and release from prison on HIV risk behavior, to identify
      optimal treatment programs for HIV-positive individuals, and to rigorously
      evaluate HIV risk-reduction interventions for incarcerated people--particularly
      those focused on the period of community re-entry. Finally, research and activism
      are needed to impact structural factors impeding HIV-prevention efforts with
      correctional populations.

PMID- 16639114
TI  - Epidemiology of mental illness in a correctional system.
AB  - PURPOSE OF REVIEW: Reports of higher than community rates of mental disorder in
      incarcerated populations first appeared in the mid-1970s. These findings have
      been confirmed over the past three decades in numerous studies across a wide
      spectrum of forensic settings. Recent research has benefited from enhanced
      methodological sophistication, and reliable rates across clinical domains and
      divergent forensic population groups are now available. This article reviews the
      literature on the prevalence of mental illness in forensic settings over the past
      10 years, with special reference to specific subgroups. RECENT FINDINGS: Overall
      rates of any mental disorder, including personality disorder and addiction,
      remain high, in general ranging between 55% and 80%. The findings of recent,
      systematic surveys and of 22 studies reviewed here reveal rates of psychosis that
      are several times higher in correctional settings than in the community. Mood
      disorder rates are elevated also, with higher morbidity reported for women than
      for men. Findings in specialized populations indicate similarly elevated rates of
      mental disorder among adolescent and geriatric prisoners, while addiction rates
      rank highest across all population domains. SUMMARY: The prevalence of
      psychiatric illness in correctional settings is significantly elevated, with
      higher than community rates reported for most mental disorders. It is estimated
      that in the USA one in five incarcerated persons is afflicted with major
      psychiatric illness; with an estimated 9-10 million persons imprisoned worldwide,
      the burden of psychiatric illness in this vulnerable and marginalized population
      poses a serious challenge to researchers and clinicians alike.

PMID- 16639115
TI  - Latin American aspects of refusal to undergo court-ordered forensic psychiatric
      examination.
AB  - PURPOSE OF REVIEW: Forensic psychiatric examinations have gained increasing
      importance in many areas of the law. When individuals refuse to undergo court
      ordered examinations of this kind, experts have to solve the tension between
      ethical and technical problems and judicial requirements. The purpose of this
      review is to obtain research information and standards related to refusal to
      undergo court-ordered forensic psychiatric examinations. RECENT FINDINGS: In
      Latin American countries, the literature on this subject is limited. The dominant
      position is that court-ordered examinations should be conducted even when the
      individual refuses to undergo examination, following technical and ethical
      considerations. SUMMARY: Experts should consider the mental competency of
      individuals and whether they pose a danger to themselves or others. In cases when
      the defendant refuses to undergo a court-ordered psychiatric examination, the
      expert, in collaboration with the judge, should decide upon an appropriate and
      reasonable means to conduct such an evaluation.

PMID- 16639116
TI  - Competence to be sentenced.
AB  - PURPOSE OF REVIEW: Competence to be sentenced, or lack thereof, is not frequently
      claimed in legal proceedings. This paper reviews the concept and possible
      forensic psychiatric applications. RECENT FINDINGS: This topic has achieved
      prominence because of recent rulings imposed by the US Supreme Court that
      prohibit execution of mentally impaired and under-age individuals. The most
      recent contributions focus on standards for evaluating competence to be sentenced
      and on analyzing the need for involuntary treatment of those who for psychiatric
      reasons have lost the capacity to stand trial. SUMMARY: Competence to be
      sentenced may be defined as a component of a general capacity to undergo legal
      proceedings, beyond just fitness to stand trial. It applies specifically to the
      time between the moment the process ends and the moment a sentence is rendered.
      This paper reviews general capacity to participate in legal proceedings as a
      concept that allows a person to intervene fully in his or her defence in a trial
      that is just and fair, and the different moments at which mental capacity to
      proceed may be limited or absent. There are no specific guidelines for evaluating
      competence to be sentenced, so instead we review the basic criteria for general
      capacity to participate in legal proceedings, including the capacity to mount a
      defence, to be sentenced and to serve a sentence. Because forensic evaluations
      are needed for assessment of capacity, the paper provides guidelines on how to
      organize the assessment and the report.

PMID- 16639117
TI  - Prevalence and characteristics of mental disorders in jails and prisons.
AB  - PURPOSE OF REVIEW: The published literature from 2004 on mental disorders in
      jails and prisons was reviewed. RECENT FINDINGS: A number of important studies on
      prisoner suicide, older prisoners, prison medical services and inmate mental
      health are highlighted, which provide useful potential interventions to improve
      the care of mentally ill prisoners. Relevant pieces on ethical issues are also
      discussed. SUMMARY: Despite increasing prison populations worldwide and robust
      evidence that serious mental disorders are common in inmates in Western
      countries, many key issues in the treatment of mentally disordered prisoners
      remain unanswered. In addition, the evidence base on the nature and prevalence of
      mental disorders in prisoners in non-Western countries remains small.

PMID- 16639118
TI  - Restraint and seclusion in psychiatric inpatient wards.
AB  - PURPOSE OF REVIEW: Despite the controversy over the use of seclusion and
      restraint, these measures are commonly used to treat and manage disruptive and
      violent behaviour. This review summarizes recent research on the use of seclusion
      and restraint, and measures taken to reduce their use. RECENT FINDINGS: Lately,
      prominent international recommendations have aimed to restrict the use of
      seclusion and restraint, and reminded that they should only be used in
      exceptional cases, where there are no other means of remedying the situation and
      under the supervision of a doctor. The use of seclusion and restraint has
      remained prevalent, but there are serveral innovative programmes that have
      succeeded in controlling and reducing their use. Staff attitudes about seclusion
      and restraint have changed little in the last few years. SUMMARY: There is a need
      for novel methods to treat violence and the threat of violence on psychiatric
      wards. Violence is a complex phenomenon that needs to be met with a
      multiprofessional approach. Customer involvement in this work is required. The
      assessment of the effectiveness of programmes aiming to minimizing seclusion and
      restraint has been hampered by the lack of parallel control groups and there is a
      need for cluster-randomized trials. When studying these interventions, the safety
      of staff and patients should be included as on outcome measure.

PMID- 16639119
TI  - Mental health practice in Arab countries.
AB  - PURPOSE OF REVIEW: This review deals with the current situation of mental health
      practice in Arab countries. Despite the complexity and importance of the topic,
      the Arab world still shows a lack of awareness regarding mental health problems
      and a dearth of mental health services and professionals. The main purpose of
      this paper is to examine changes in the area of mental health, and what still
      needs to be developed or investigated. RECENT FINDINGS: Mental health patients in
      Arab countries tend to express their psychological problems in terms of physical
      symptoms, thereby avoiding the stigma attached to mental illness. They also tend
      to underutilize mental health services and to hold negative attitudes toward
      formal mental health services. Reliance upon a deity and religious leaders as a
      means of coping with mental health issues is another prevalent theme in the Arab
      world. Another issue is that of mental health practices in politically volatile
      and violent regions, where higher rates of mental health problems and psychiatric
      diagnoses have been found. In addition, women in Arab/Muslim countries are at
      paramount risk from mental health problems. SUMMARY: The findings have
      implications for professional service delivery. Further research, intervention
      and activism are needed in the field of mental health systems in Arab countries
      to improve awareness of mental health problems. Further research is also needed
      regarding issues such as cultural competence and the suitability of mental health
      treatment and services for the non-Western communities in many Arab/Muslim
      countries.

PMID- 16639120
TI  - Is it possible to carry out high-quality epidemiological research in psychiatry
      with limited resources?
AB  - PURPOSE OF REVIEW: This review covers the epidemiological research from
      developing countries to identify the scope of research in the various aspects of
      epidemiology and the strengths of research. The period covered is June 2004 to
      June 2005. The literature survey used searches of Medline, key psychiatric
      journals and personal correspondence with leading psychiatric researchers from
      developing countries. RECENT FINDINGS: There is a new interest in epidemiological
      studies in developing countries. These studies have been driven by three factors,
      namely international collaboration; specific situations like disasters, terrorism
      and severe acute respiratory syndrome; and international attention to specific
      topics like maternal depression. There is limited long-term research on specific
      conditions. There are a number of leads suggesting local social-cultural factors
      contribute to the distribution of psychiatric problems. Child psychiatry
      continues to be low in priority. There is also lack of research in areas such as
      personality disorders and organic psychiatric disorders. SUMMARY: It is possible
      to carry out high quality epidemiological research in developing countries. Such
      research has provided new insights into the distribution, causation, course and
      outcome of mental disorders. There is need for greater attention to the
      development of epidemiological assessment tools to suit local conditions.
      Specific centers/institutions developing long-term research interests on specific
      subjects would be valuable for future efforts. There is also need to widen the
      conditions to be studied.

PMID- 16639121
TI  - The autonomy of professionals and the involvement of patients and families.
AB  - PURPOSE OF REVIEW: The involvement of patients/service users and their
      families/caregivers in the field of mental health has been of interest for
      several years. It is timely to review what has been learned about involvement; to
      understand where and how involvement has been implemented; and to explore factors
      which influence the effectiveness of implementation. Recent literature on user
      involvement and its implications for professional practice forms the focus of
      this review. Material is drawn largely from Europe, North America and
      Australasia, since this reflects where there is most interest in this topic.
      Papers outside of mental health are included where they further illuminate issues
      under discussion. RECENT FINDINGS: The involvement of users/patients and their
      caregivers is an important aspect of the care and treatment of mental illness
      extending across health and social care. Involvement has implications for
      professional practice including the negotiation of treatment, the coordination of
      care and communication strategies. Tensions may emerge during the process of
      effectively implementing patient/family involvement, but the autonomy of
      professionals is not usually a factor. SUMMARY: There is no singular definition
      of involvement. There has been growth in the levels of user/caregiver
      involvement, particularly in community-based provision and within transition
      processes from hospital to community-based treatment. There is no suggestion that
      involvement is widespread. Implementation of involvement should be underpinned by
      effective communication on the part of professionals and recognition of service
      users and caregivers as partners in processes of treatment and recovery.
      Implementation is most effective when supported by appropriate organizational
      policies and integrated into the education of health professionals.

PMID- 16639122
TI  - Coercion, involuntary treatment and quality of mental health care: is there any
      link?
AB  - PURPOSE OF REVIEW: This paper summarizes major results and debates in the field
      of coercive or involuntary treatment of the mentally ill and how these relate to
      the quality of care, as published in literature during 2002 and 2003. RECENT
      FINDINGS: Studies focus on four major issues: involuntary hospital placement and
      treatment of mentally ill patients, compulsory outpatient treatment, attitudes
      towards or perceived coercion, and ethics of coercive measures in mental health
      care. Studies suggest a complex correlation between the involuntary placement of
      mentally ill patients, coercive measures, and outcomes. Outcome indicators for
      the quality of mental health care are not standardized, but vary with the point
      of view of the individual or collective assessor. None of the results question
      the necessity or the legality of involuntary treatments or conclude to refrain
      from employing coercive measures in mental health care if these cannot be
      avoided. Many results of research on attitudes towards involuntary treatments or
      perceived coercion suggest an acceptance of the application of coercive measures,
      even by the persons concerned, if the legal conditions are clearly defined.
      Research standards or study designs may benefit from some improvement. Study
      samples usually are small and only in rare cases has their selection been
      representative. SUMMARY: Research activities are remarkably few in number,
      especially considering the frequency of involuntary measures and the
      controversial perception or discussion of these measures among the persons
      concerned, professionals, or a wider public. Many basic research questions still
      remain to be adequately addressed, such as the long-term effects of involuntary
      treatment.

PMID- 16639123
TI  - The geography of mental health: an established field?
AB  - PURPOSE OF REVIEW: The purpose of this review is to offer an outline introduction
      to a field of inquiry known as the geography of mental health (or mental health
      geographies). Since this is the first time the field has been reviewed in this
      journal, attention will be paid to the history of the field, not just recent
      findings. RECENT FINDINGS: Research has chiefly, but not exclusively, tackled (i)
      the spatial epidemiology of mental ill-health and (ii) the changing locational
      associations of mental health care. SUMMARY: This review has concentrated chiefly
      on contributions to this field of inquiry made by researchers with a background
      in the academic discipline of geography. While there are 'geographical'
      contributions made by workers from other disciplinary backgrounds, there is
      arguably something distinctive, particularly in the most recent scholarship,
      arising from a theorized sensitivity to the entangled relations of mental health,
      society, space and environment.

PMID- 16639124
TI  - Bibliography. Current world literature. Mental retardation and developmental
      disorders.

PMID- 16639126
TI  - Professional capability: evidence- and values-based frameworks for psychiatrists
      and mental health services.

PMID- 16639127
TI  - What do children and young people want from mental health services?
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review the literature
      reporting on children and young people's views on child and adolescent mental
      health services. RECENT FINDINGS: The review demonstrates that there is limited
      research exploring the views of children and young people regarding mental health
      services. Despite its limitations, the research available shows that young
      people, their parents and healthcare providers often have different expectations
      of services. Young people want accessible services staffed by those they are able
      to trust and who demonstrate an ability to listen; above all, young people want
      to be involved in the decisions made about them. SUMMARY: To date, children and
      young people have not been actively engaged or involved in service development.
      This is an evolving field and we need to ensure that existing evidence is taken
      into account as well as investigating further the views of young people. Child
      and adolescent mental health services need to consider how we serve young people,
      particularly children, whose perspectives may differ from those of their parents.

PMID- 16639128
TI  - Involving patients and their carers in educating and training practitioners.
AB  - PURPOSE OF REVIEW: We summarize and discuss recent work that highlights the role
      of patients and carers in educating practitioners in the light of earlier
      findings. RECENT FINDINGS: In today's National Health Services in the UK, a
      changing value base is emerging based on the participation of practitioners,
      patients and carers, with each group contributing to the education and training
      of healthcare professionals. The role of patients and carers in education is
      changing as the value of their experience and expertise is acknowledged. Now
      professionals are more actively recognizing that service users can contribute
      usefully to teaching in more unique ways, as 'experts' in their illness. They
      bring different perspectives and ways of thinking that can instill a new
      dimension to delivering healthcare services and training. Their expertise is
      defined by experience, and this different perspective gives them a unique role in
      teaching. They represent a potential teaching resource for medical education that
      is grossly underutilized. SUMMARY: Patients and carers are experts in their
      particular circumstances and blending their expertise with that of professionals
      is likely to contribute to the best outcome in a particular situation. They are a
      valuable resource as potential teachers at all stages of medical education.

PMID- 16639129
TI  - Time trends in child and adolescent mental disorders.
AB  - PURPOSE OF REVIEW: 1995 saw the publication of a major review of time trends in
      psychosocial disorders of youth across the second half of the twentieth century.
      It found evidence for substantial increases in rates of youth crime, alcohol and
      drug use, depression and suicide in most industrialized countries in the decades
      following the Second World War, slowing in some instances in the 1980s. Ten years
      on, we review findings on more recent trends in rates of these and other
      indicators of child and adolescent mental health. RECENT FINDINGS: Prevalence
      estimates for autism spectrum disorders have increased in recent decades, as has
      public and professional awareness of hyperactivity and attention deficits. Trends
      in adolescent conduct problems, and in alcohol and drug use, appear to reflect
      culture-specific influences. Rates of suicide among young males, and self-harm
      among females have risen in many countries in recent years; trends in emotional
      disorders are more varied, but there is little evidence for any rise in rates of
      anorexia nervosa. Although some contributors to these trends have been
      identified, much remains to be learned about the key risks involved. SUMMARY:
      Monitoring time trends in child and adolescent mental health is essential for
      service planning; knowledge of changing trends can also provide important
      pointers to potential risk factors. Current data sources allow relatively
      reliable tracking of trends in some areas, but remain severely limited in others.
      Further research is needed to understand the mechanisms underlying recently
      identified trends in child and adolescent mental health.

PMID- 16639130
TI  - Parenting and the development and prevention of child mental health problems.
AB  - PURPOSE OF REVIEW: The government is recognizing the need to deal with the
      growing numbers of antisocial young people through investing in early preventive
      parenting support. It is important that the services provided are evidence-based
      and delivered effectively. This review briefly discusses the contribution of
      parenting to the development of child mental health difficulties, particularly
      externalizing problems, and reviews some effective early intervention preventive
      programmes. RECENT FINDINGS: Over 30 years of research have established both that
      parenting behaviours influence the development of childhood conduct disorders and
      that behavioural family interventions targeting specific parenting skills are the
      most effective way of preventing or reducing child behaviour problems. Until
      recently, however, those children at highest risk have often had the poorest
      outcomes from intervention. Recent research has identified the factors that make
      parenting interventions effective and how to engage the multi-stressed, hard-to
      reach families whose children are most at risk. SUMMARY: Research has identified
      risk factors that are associated with the development of conduct disorder and
      affect the quality of parenting. This has made it possible to provide preventive
      interventions, targeting families that are most at risk. Evaluations have shown,
      however, that getting effective preventive services to those most at risk is not
      straightforward and programmes need to address the problem of recruiting parents
      who, by virtue of their multiple problems, have traditionally been hard to
      engage. Emphasis is placed on the importance of using evidenced-based programmes
      in service settings in ways that are effective.

PMID- 16639131
TI  - Evidence-based management of conduct disorders.
AB  - PURPOSE OF REVIEW: It is becoming increasingly apparent that antisocial children
      often grow up to inflict considerable damage on others at a high cost, and also
      lead very impoverished lives themselves. There is rising public and governmental
      concern to get on top of aggressive and criminal behaviour, which is especially
      prevalent in the socially and economically disadvantaged. RECENT FINDINGS: While
      parent training has been around for some 30 years, it has now been supplemented
      by efficacious child problem-solving and teacher-training programmes. For severe
      delinquency, community-based multisystemic interventions are reasonably effective
      when applied diligently. They cover social skills, and keep youths very closely
      supervised while giving them immediate rewards for compliance. SUMMARY: Despite
      popular impressions to the contrary, a lot is known about the causes of
      antisocial behaviour and conduct disorders, and now there are effective
      interventions to reduce it. However, many policymakers and commissioners are
      still unaware that effective programmes exist, or that when implemented,
      insufficient attention is paid to the need for fidelity to the model used and to
      the development of therapist skill. Effectiveness is then often disappointing in
      'real life' conditions. However, when these factors are addressed, the evidence
      is clear that substantial gains can be made.

PMID- 16639132
TI  - Smoking and young people's mental health.
AB  - PURPOSE OF REVIEW: This review addresses the evidence on smoking and young
      people's mental health, reported during 2004. RECENT FINDINGS: Research studies
      have confirmed the previously reported epidemiological associations of smoking
      with gender, race and social class, as well as suspected risk factors and
      antecedents. Among youths, the prevalence of smoking varies across subgroups of
      the population, classified by race/ethnicity and social class. Gender differences
      in smoking vary cross-nationally. Smoking among youths is higher when parents,
      siblings, or peers smoke. Smoking is also higher in youths with histories of
      early conduct problems, drinking and illegal drug use, depression, and suicidal
      behaviors. The protective role of youth involvement in sports and the lesser
      opportunity to smoke among youths involved in religious practice were also
      confirmed. Among young people, early conduct problems and associated early onset
      of daily smoking predict a greater likelihood of becoming nicotine dependent. The
      interpretation of the high smoking rate among schizophrenic patients as self
      medication has been challenged by a recent study that reported that smoking
      predicted subsequent first hospitalization for schizophrenia. New findings
      suggest that young persons who experienced their first exposure to nicotine as
      relaxing are at elevated risk for becoming nicotine dependent. SUMMARY:
      Longitudinal cohort studies and cross-sectional studies have been published on
      smoking and young people's mental health. These studies describe smoking
      correlates and identify predictors of negative outcomes of smoking, as well as
      predictors of nicotine dependence, smoking initiation, and smoking cessation.

PMID- 16639133
TI  - Deliberate self-harm in children and adolescents: a research update.
AB  - PURPOSE OF REVIEW: We outline research developments in 2004 and early 2005
      published in English language journals on deliberate self-harm among children and
      adolescents up to the age of 18 years. RECENT FINDINGS: The main issue of concern
      in recent times has been the risk/benefit profile of using antidepressants,
      especially selective serotonin reuptake inhibitors, in depressed children and
      adolescents. Other important topics include treatment approaches, particularly
      cognitive behaviour therapy, dialectical behaviour therapy and multisystemic
      therapy, barriers to help seeking, the Internet and prevention. SUMMARY: Rates of
      deliberate self-harm appear to be rising among young people. Risk factors
      associated with deliberate self-harm are becoming clearer and the evaluation of
      treatments is progressing. However, the recent conflicting evidence and
      guidelines regarding selective serotonin reuptake inhibitors and suicidality are
      presenting major difficulties for clinicians. The role of the Internet and
      initiatives to prevent suicidal behaviour in adolescents require further
      research.

PMID- 16639134
TI  - Eating disorders in children and adolescents: an update.
AB  - PURPOSE OF REVIEW: Children and adolescents with eating disorders frequently
      present to child mental health and paediatric services and have significant
      morbidity, psychosocial impairment and mortality. Efforts to treat these
      individuals have been hampered by a poor evidence base for effective
      interventions. This article reviews research published during 2004 with a primary
      focus on this challenging clinical area. RECENT FINDINGS: Research published
      during 2004 has replicated past epidemiological findings and expanded our
      understanding of the relationship of family meal structure and disordered eating.
      Research has provided assistance in the well known clinical conundrums of
      excessive exercising in anorexia nervosa and predicting when return of menses
      will occur. There has also been clarification of adolescent bingeing. Potential
      advances include a new, noninvasive method of measuring body composition and
      investigations in adolescents on leptin, neuro and gastrointestinal peptides.
      Importantly, further evidence of the effectiveness of family therapy for anorexia
      nervosa and short-term benefits from intervention programs have been published.
      SUMMARY: The research base that will influence clinical practice in child and
      adolescent eating disorders is increasing. More research is required in all areas
      of intervention.

PMID- 16639135
TI  - Child maltreatment, child protection and mental health.
AB  - PURPOSE OF REVIEW: This review summarizes advances in our understanding of child
      maltreatment and the implications thereof for physical, psychological and social
      development, with special emphasis on mental health aspects. RECENT FINDINGS:
      Methodological problems persist. These may be related in part to an over-emphasis
      on type of maltreatment, to the detriment of consideration of degree and extent
      of maltreatment. They may also be related to inadequate application of a
      comprehensive model of maltreatment and its consequences. Recent studies
      underline the inter-relatedness and cross-over between different types of child
      maltreatment and family violence. Research also underlines the extent to which
      child maltreatment is a major public health crisis internationally. Effects are
      seen on physical health and development as well as mental health, and it is
      becoming increasingly evident that these outcomes are inextricably linked to one
      another. There are encouraging signs that certain interventions are effective.
      SUMMARY: There is a need for a more sophisticated model of child maltreatment
      that includes not only degree but also the extent to which basic developmental
      needs are overridden when children are maltreated, and that includes children's
      responses to maltreatment as a mediating influence. More studies are needed of
      samples of children who have been maltreated in order to gain a better
      understanding of how maltreatment distorts the trajectory of normal development.
      Crucially, we need more research on intervention, including both case management
      and psychological treatment approaches.

PMID- 16639136
TI  - Impact, psychological sequelae and management of trauma affecting children and
      adolescents.
AB  - PURPOSE OF REVIEW: In this review we examine the most recent literature on the
      impact, psychological sequelae and management of trauma affecting children and
      adolescents. We focus on consequences of early traumatic events in childhood,
      adolescence and adulthood; mediating variables (risk and protective factors)
      intervention strategies and available treatments. RECENT FINDINGS: Increasingly
      often, mental health professionals are being asked to address the needs of
      children and adolescents who have been exposed to traumatic events, either as
      individuals or in groups. Studies on a wide range of age groups, populations and
      types of trauma revealed that traumatized children and adolescents are at high
      risk for developing a range of different behavioural, psychological and
      neurobiological problems. Social support may have a protective effect on the
      relationship between exposure to traumatic events and psychosocial symptoms.
      SUMMARY: Several recent studies analyze a wide range of early traumatic events
      that may be directly or indirectly experienced by youth. These studies raise many
      fundamental questions such as validity of current diagnostic criteria for post
      traumatic stress disorder, comorbidity with anxiety, depressive disorders and
      childhood traumatic grief symptoms. Vulnerability and protective factors, mainly
      gender, age and social support are considered. A common problem in research into
      the impact of trauma on children is the presence of many limitations: studies are
      often retrospective, use self-report questionnaires and the results may not be
      generalizable (i.e. they are trauma or population specific). There is a lack of
      well designed studies, addressing in particular treatments for post-traumatic
      symptoms in children and adolescents.

PMID- 16639137
TI  - Psychiatric comorbidity in children and adolescents.
AB  - PURPOSE OF REVIEW: This review critically discusses recent research findings on
      psychiatry comorbidity in children and adolescent persons. RECENT FINDINGS:
      Several epidemiological studies have confirmed previous findings in relation to
      the high rates of psychiatric comorbidity in children and adolescents. In
      particular, psychiatric comorbidity has been detected in children with substance
      abuse, and with conduct and oppositional defiant, anxiety and attention deficit
      hyperactivity disorders. These studies have also investigated the impact
      comorbidity has on symptom presentation, outcome and service utilization.
      Although the presence of concurrent psychiatric disorders in children and
      adolescents is well established, there has been limited research on the need for
      different treatment modalities in children suffering from more than one disorder.
      SUMMARY: It is widely accepted that children and adolescents frequently present
      with more than one psychiatric diagnosis. The substantial variation in
      psychiatric comorbidity found in the literature may be due to the different
      methods of data collection as well as to the classification system used. Whether
      children and adolescents fulfil diagnostic criteria for a mixed condition
      (International Classification of Diseases-10) or multiple disorders (Diagnostic
      and Statistical Manual of Mental Disorders-IV), it is important that the
      concurrent psychopathology be recognized and treated.

PMID- 16639138
TI  - Substance misuse and psychiatric comorbidity in adolescents.
AB  - PURPOSE OF REVIEW: Many young people are misusing and becoming dependent on
      multiple substances (especially nicotine, alcohol, and cannabis), with a complex
      variety of psychological effects. RECENT FINDINGS: Analysis of interactions
      between smoking, drinking, and cannabis use indicates that the relationship
      between substance use and psychiatric comorbidity is primarily explained by
      regular smoking. In some studies the use of cannabis on a regular basis was
      associated with an increased risk of psychiatric illness. This is by no means the
      case for all studies, so this area of work remains controversial. Children with
      attention deficit hyperactivity disorder who are substance misusers have a poorer
      prognosis than those without it so there is concern about treatment with
      stimulant drugs: this fear appears not to be substantiated by one study. Young
      people with anxiety disorders are at increased risk of substance use disorders.
      Clinical trials for adolescent substance abuse treatment have provided support
      for the benefits of cognitive behavioural interventions. There is an accumulating
      evidence base for pharmacological treatment for adult substance misusers that can
      inform treatment for younger patients. It is estimated that, of those adolescents
      who were likely to be in need of help, only about 9% received treatment. SUMMARY:
      Since psychiatric disorders beginning in childhood may continue into adult life,
      there is an opportunity to intervene to prevent or reduce conditions complicated
      by substance misuse, if services are accessible. The need for longitudinal work
      is vital to explore the patterns of comorbidity, and implement and evaluate
      appropriate treatment interventions.

PMID- 16639139
TI  - Developing primary mental healthcare for children and adolescents.
AB  - PURPOSE OF REVIEW: Governmental initiatives to enhance child and adolescent
      mental healthcare are giving renewed impetus to work in primary care. This review
      identifies and discusses critically new findings in this area. RECENT FINDINGS:
      Research reviews and new studies continue to highlight the burden of unidentified
      and hence untreated psychopathology among children attending primary care.
      Expression of parental concern appears to provide important help in improving
      recognition. Shared protocols have been developed for primary care use for
      clinical conditions such as attention deficit hyperactivity disorder, but
      adherence to protocols is still limited. Randomized controlled trials have shown
      the feasibility and efficacy of suitably adapted therapeutic interventions for
      adolescent depression in primary healthcare and in educational settings. Surveys
      indicate a significant amount of child and adolescent mental health work by
      social services in countries such as the UK, and attest to the usefulness of
      protocols to attend to children in foster care. The new role of primary mental
      health worker has the potential to help support the interface between primary and
      specialist child and adolescent mental health services. SUMMARY: There is
      increased interest in further clarifying and enhancing the role of primary care
      child and adolescent mental health services.

PMID- 16639140
TI  - Inpatient services.
AB  - PURPOSE OF REVIEW: Inpatient services constitute the most highly specialized
      child and adolescent mental health provision and cater for the most severe
      disorders in this age group. In view of a number of mapping and audit initiatives
      in the UK in recent years and changing influences on admission policies
      worldwide, it is timely to review their function and effectiveness. RECENT
      FINDINGS: Recent attention has focused on describing service configurations and
      auditing against standards. National surveys of cost, referral processes and
      patient satisfaction are in progress in the UK. There seems to be an
      international trend toward a more severe, comorbid and aggressive patient group
      being admitted to inpatient services. There is a shortage of quality research
      into clinical outcomes of inpatient treatment, but controlled trials comparing
      hospital treatment with intensive community management are emerging. SUMMARY:
      Inpatient descriptive studies and uncontrolled outcome studies predominate in the
      literature. Although many children and adolescents benefit from admission to
      mental health inpatient facilities, the specific advantages of admission over
      intensive community management are uncertain.

PMID- 16639142
TI  - Bibliography. Current world literature. Child and Adolescent psychiatry.

PMID- 16639141
TI  - Patients as parents and young people approaching adulthood: how should we manage
      the interface between mental health services for young people and adults?
AB  - PURPOSE OF REVIEW: The present review discusses critically recent research
      findings (published during the period 2003-2004) on the mental health needs of
      young people in transition (old adolescents and young adults), including those of
      young parents. Also, the evidence on effective interventions and service models
      is considered. RECENT FINDINGS: Emerging evidence indicates that young people
      have high rates of mental health needs (in addition to high prevalence of
      psychiatric disorders) that may be related to life transitions. These needs often
      fall between the remit of adolescent/adult and mental health/social care
      services, and therefore are not adequately met. With the exception of mental
      health interventions for early psychosis and psychosocial programmes for teenage
      parents, there is very limited knowledge on how best to meet the mental health
      needs of young people in transition. SUMMARY: It is widely recognized that young
      people in transition require services and interventions tailored to their
      characteristics, rather than a mere extension to either child/adolescent or adult
      services. Recent policies and research findings have led to the development of
      early psychosis interventions, with initial encouraging messages. Similar
      initiatives are required for young people with nonpsychotic disorders.

PMID- 16639144
TI  - Understanding alcohol misuse and comorbid psychiatric disorders.
AB  - PURPOSE OF REVIEW: This review examines the relationship between alcohol misuse
      and comorbid psychiatric disorders, and the treatment of these comorbid
      disorders. In the past, the literature was dominated by papers describing
      prevalence, clinical services and comorbidity with schizophrenia. It is now
      advancing into areas such as the relationship between alcohol misuse and the
      anxiety disorders, affective disorders and eating disorders, and considering the
      diagnostic paradigm. Knowledge is also emerging about the influences of genetics
      and adverse effects over different stages of the life cycle in the development of
      these disorders. RECENT FINDINGS: Recent studies have examined the relationships
      between alcohol dependence and psychiatric illness, particularly anxiety and
      depression, but also subthreshold conditions. Childhood trauma, having parents
      with substance dependence and genetic factors influence the development of
      alcohol and comorbid psychiatric disorders. There is a genetic contribution to
      suicidal behaviour in alcohol-dependent patients. Early diagnosis is important.
      Alcohol Use Disorders Identification Test scores on admission to psychiatric
      hospital were found to correlate with suicidal ideation and behaviour. In
      patients with alcohol use disorders, treatment for depression works better after
      a period of abstinence. Abstinence alone can help for anxiety disorders. High
      intensity services had better outcomes for this comorbid population than less
      intensive services. SUMMARY: Depression in patients with alcohol use disorders
      cannot be ignored. Treatment of depression alone will not help the alcohol use
      problems. All psychiatric inpatients should be screened for alcohol use disorders
      as part of their risk assessment. Research is focusing more on examining the
      complexities of these disorders, but there are no specific pharmacotherapies to
      treat particular comorbid conditions.

PMID- 16639145
TI  - Innovative approaches to intervention for problem drinking.
AB  - PURPOSE OF REVIEW: To critique the recent literature on telephone, correspondence
      based, and computerized interventions for alcohol problems, which enhance or
      substitute for practitioner-delivered treatments. RECENT FINDINGS: There is an
      unmet need for screening, assessment and intervention for alcohol problems, in
      part because of the difficulty in accessing such treatment within the current
      health care system. Research on the efficacy of correspondence or electronic (for
      example Internet-based) interventions is beginning to emerge. In the period 2003
      2004 we identified nine acceptability or feasibility studies of these approaches
      and seven efficacy trials covering a wide range of settings. These modes of
      intervention are acceptable to patients and the public, and with careful
      planning, can be implemented in a variety of settings. Treatment trials
      demonstrate the efficacy of these interventions in reducing hazardous drinking by
      university students, in delaying initiation of heavy drinking in children and
      adolescents, and, intriguingly, in addressing insomnia among recovering
      alcoholics. SUMMARY: There is strong support among potential users for alcohol
      interventions that employ telephone assistance, written correspondence, and the
      Internet. These new technologies offer the prospect of increasing the reach of
      interventions for problem drinking and being cost-effective alternatives or
      supplements to face-to-face health service delivery.

PMID- 16639146
TI  - Emerging research on methamphetamine.
AB  - PURPOSE OF REVIEW: To describe and review the literature published on
      methamphetamine in 2003-2004, with a particular focus on patterns of use, its
      effects on the user and society, and progress being made towards effective
      treatment strategies. RECENT FINDINGS: The methamphetamine epidemic continues to
      grow, dominating drug use trends in many parts of the world, and signifying an
      increasing need for effective treatment. In addition to the already-documented
      physical effects of the drug, preliminary evidence suggests methamphetamine
      dependence may cause long-term neuronal damage. Recently abstinent users have
      been found to do poorly on neurocognitive tests of attention and motor skills,
      both factors that can adversely affect treatment outcomes. Methamphetamine use is
      also implicated in aggression and violence and there are increasing presentations
      to emergency rooms. It also affects the developing fetus, as well as children and
      adults who are exposed to toxic chemicals at laboratory sites. Outpatient
      programs, such as the Matrix Model, show improved in-treatment performance. Case
      management was found to be an effective intervention. Agonist-type
      pharmacotherapy in combination with quality behavioral therapy should produce
      benefit and a reduction in risks caused by stimulant abuse. SUMMARY: The
      increasing evidence that methamphetamine has adverse effects on the human brain
      indicates the pressing need for effective prevention and treatment approaches.
      There is a need to take these findings, particularly those that involve cognitive
      deficits, into consideration in current treatment programs and when developing
      new treatments.

PMID- 16639147
TI  - Inhalants: not to be taken lightly anymore.
AB  - PURPOSE OF REVIEW: Until recently, inhalant abuse and dependence have been
      overlooked as serious problems, perhaps because of their relatively low
      prevalence. The purpose of this review is to summarize recent advances in our
      understanding of the consequences, pharmacology, and etiology of inhalant use,
      and how we might develop preventive and management strategies to combat abuse and
      dependence on these drugs. RECENT FINDINGS: Animal models have cast light on how
      reinforcement of inhalant use occurs, and on mechanisms of development of
      tolerance and dependence. The reinforcing effects occur principally through GABA
      and dopamine-mediated mechanisms (rather than NMDA-mediated mechanisms). Assays
      for inhalants provide greater opportunities for accurate diagnosis. In addition
      to known medical consequences of inhalant use (including death), other risks
      associated with inhalant use and addiction include addiction to other substances,
      major depression, suicide, and impaired learning and memory. SUMMARY: The
      extensive medical, psychiatric, and psychological damage that can be caused by
      inhalant use argues for much greater attention to be paid to developing
      prevention and treatment programmes for inhalant abuse and dependence. These are
      currently nonexistent, but are badly needed.

PMID- 16639148
TI  - The diagnosis and management of benzodiazepine dependence.
AB  - PURPOSE OF REVIEW: Despite repeated recommendations to limit benzodiazepines to
      short-term use (2-4 weeks), doctors worldwide are still prescribing them for
      months or years. This over-prescribing has resulted in large populations of long
      term users who have become dependent on benzodiazepines and has also led to
      leakage of benzodiazepines into the illicit drug market. This review outlines the
      risks of long-term benzodiazepine use, gives guidelines on the management of
      benzodiazepine withdrawal and suggests ways in which dependence can be prevented.
      RECENT FINDINGS: Recent literature shows that benzodiazepines have all the
      characteristics of drugs of dependence and that they are inappropriately
      prescribed for many patients, including those with physical and psychiatric
      problems, elderly residents of care homes and those with comorbid alcohol and
      substance abuse. Many trials have investigated methods of benzodiazepine
      withdrawal, of which the keystones are gradual dosage tapering and psychological
      support when necessary. Several studies have shown that mental and physical
      health and cognitive performance improve after withdrawal, especially in elderly
      patients taking benzodiazepine hypnotics, who comprise a large proportion of the
      dependent population. SUMMARY: Benzodiazepine dependence could be prevented by
      adherence to recommendations for short-term prescribing (2-4 weeks only when
      possible). Withdrawal of benzodiazepines from dependent patients is feasible and
      need not be traumatic if judiciously, and often individually, managed.

PMID- 16639149
TI  - The medical complications of heroin use.
AB  - PURPOSE OF REVIEW: Heroin use is associated with numerous adverse sequelae. As
      clinical services develop, addiction psychiatrists will increasingly be called
      upon to help identify and manage the complications of heroin use. This review
      focuses on recent research into the medical complications of heroin use and looks
      at strategies to minimize harm associated with this practice. RECENT FINDINGS:
      Mortality associated with heroin overdose has increased substantially in many
      countries. Parenteral use of opioid drugs is a central factor and other risk
      factors include polydrug use, particularly benzodiazepines and alcohol, mental
      health issues and environmental factors not conducive to resuscitation.
      Unravelling the determinants of blood-borne virus transmission continues, the
      focus shifting from needle sharing to inadvertent sharing of other injecting
      equipment. Trials addressing the challenges of antiviral therapy in injecting
      drug users are emerging. A greater understanding of the effects of opioids on
      immune functioning complements our knowledge of infection in the heroin-using
      group as well as possibly explaining the reduced response to vaccination in this
      group. SUMMARY: Medical complications of heroin affect a number of different
      organ systems. The role of the addiction specialist is to be aware of these so
      that early diagnosis and appropriate management is instituted. The latter will
      generally be done in collaboration with other specialists. The addictions
      specialist can play a significant role in the development of clinical systems to
      minimize these complications.

PMID- 16639150
TI  - Pharmacotherapy and other treatments for cocaine abuse and dependence.
AB  - PURPOSE OF REVIEW: This review examines progress being made in the treatment of
      cocaine abuse and dependence, with a particular focus on pharmacotherapies.
      Medications with apparently very different mechanisms of action have been
      reported to reduce cocaine use in controlled clinical trials in outpatient
      settings. This review will summarize the latest findings in this area. RECENT
      FINDINGS: Of all the medications tested to date, disulfiram has demonstrated the
      most consistent effect to reduce cocaine use. Several medications have been
      reported to reduce cocaine use in double-blind, placebo-controlled clinical
      trials, namely baclofen, modafinil, tiagabine, and topiramate. All
      pharmacotherapy trials in cocaine-dependent patients include a behavioral therapy
      that is common to all participants. Consequently, these pharmacotherapy trials
      can be considered to evaluate whether the medication is adding to the effect of
      the behavioral therapy. SUMMARY: Confirmatory clinical studies are necessary to
      replicate the initial efficacy findings for baclofen, modafinil, tiagabine, and
      topiramate. More research is needed in both cocaine and cocaine-alcohol dependent
      populations. Once confirmatory studies have been carried out, testing of rational
      medication combinations with different behavioral therapies is an obvious next
      step to increase the ability to manage cocaine dependence.

PMID- 16639151
TI  - Natural and complementary therapies for substance use disorders.
AB  - PURPOSE OF REVIEW: To review recent studies that have examined the efficacy of
      natural and complementary therapies as treatments for substance use disorders and
      their complications. RECENT FINDINGS: Despite increasing interest in natural and
      complementary therapies for substance use disorders, rigorous clinical studies in
      this area are few in number. Recent clinical studies, although preliminary, have
      reported potential therapeutic effects for hypericum in the treatment of smoking
      cessation, for prickly pear extract in the prevention of alcohol hangover and
      magnesium supplementation as an adjunct to methadone treatment. Other clinical
      studies have reported negative findings for ginkgo as an adjunctive treatment for
      cocaine dependence, for artichoke in prevention of alcohol hangover, and
      acupuncture for alcohol withdrawal. Relevant findings from animal studies are
      also discussed. Neither vitamin E nor Liv 52 had a useful effect in alcohol
      related liver disease. A study of silymarin in baboons, which was undertaken in
      an attempt to untangle the conflicting findings of human studies, reported a
      potential for this compound to prevent liver injury. There is increasing
      awareness of safety issues associated with complementary therapies. Safety issues
      pertinent to substance use treatment are discussed in this review. SUMMARY:
      Several pharmacological and psychosocial treatments for substance use disorders
      are solidly evidence-based and improve both individual and public health
      outcomes. At this stage, there remains insufficient evidence to support the use
      of natural and complementary therapies as a primary intervention for substance
      use disorders. Further clinical trials are required to clarify the potential role
      of particular agents.

PMID- 16639152
TI  - Ethical issues in brain banking.

PMID- 16639153
TI  - The psychopathology of schizophrenia and the presence of neurological soft signs:
      a review.
AB  - PURPOSE OF REVIEW: The symptoms of schizophrenia cluster in at least three
      subtypes: positive, negative, and disorganized. The study of these subtypes and
      their phenotypic markers may help our understanding of the pathophysiology of
      schizophrenia. Among the markers of schizophrenia are minor neurological signs,
      which are abnormalities in sensory and motor performance elicited by clinical
      examination. Evidence on whether neurological abnormalities are associated with a
      specific symptom subtype is considered. As recent studies have often evaluated
      individuals at their first psychotic episode who are antipsychotic naive, a
      review would help to clarify whether neurological soft signs are part of a
      neurodysfunction that underlies schizophrenia rather than the consequence of
      degenerative processes or of long-term pharmacological treatment. RECENT
      FINDINGS: A consistent association seems to emerge between an excess of
      neurological soft signs and severe negative symptoms. Signs associated with
      negative symptoms remain stable over time, and may characterize a subgroup of
      patients with poor illness course and outcome. Some signs, such as motor
      dysfunction, may be associated with a worse profile of positive symptoms, and may
      improve as symptoms improve. Too few studies have evaluated the association
      between neurological soft signs and disorganization symptoms to suggest or
      disconfirm any relationship. SUMMARY: Finding an association between neurological
      soft signs and one (or more) dimension(s) of schizophrenia in never treated
      patients may explain which neurological dysfunction is an intrinsic
      characteristic of the illness. The comparability of future studies can be
      improved by using the same structured rating scale for neurological soft signs
      and psychopathology, and by a better characterization of patient samples.

PMID- 16639154
TI  - Neuropsychiatric consequences of traumatic brain injury: a review of recent
      findings.
AB  - PURPOSE OF REVIEW: Behavioral and psychiatric disturbances are the more frequent
      consequences of traumatic brain injury and major determinants of the quality of
      life of patients. This review was designed to familiarize the reader with the
      more recent work published in this field. RECENT FINDINGS: We have now a more
      consistent view of the epidemiology of post-traumatic brain injury psychiatric
      disorders both in adult and pediatric populations. Mood disorders, anxiety
      disorders and substance use disorders are the more prevalent psychiatric
      diagnoses among traumatic brain injury patients. The phenomenological
      characteristics and clinical correlates of major depression, post-traumatic
      stress disorder, alcohol use disorders, and post-traumatic brain injury attention
      deficit hyperactivity disorder have been studied in more detail. Newer
      structural, metabolic and functional neuroimaging techniques help to clarify the
      pathogenesis of these disorders. In turn, this knowledge may lead to the
      implementation of more efficient therapeutic interventions. Unfortunately,
      controlled treatment studies have been the exception in the field, and treatment
      decisions usually lack adequate empirical support. SUMMARY: Recent advances in
      the basic neuroscience of traumatic brain injury as well as in behavioral
      genetics, social science and neuroimaging techniques should contribute to a
      better understanding of the pathophysiology of the psychiatric disorders
      occurring after the injury. There is a great need for randomized, double-blind,
      placebo-controlled trials to establish the most effective treatments for these
      disorders.

PMID- 16639155
TI  - Outcome from mild traumatic brain injury.
AB  - PURPOSE OF REVIEW: The focus of this review is outcome from mild traumatic brain
      injury. Recent literature relating to pathophysiology, neuropsychological
      outcome, and the persistent postconcussion syndrome will be integrated into the
      existing literature. RECENT FINDINGS: The MTBI literature is enormous, complex,
      methodologically flawed, and controversial. There have been dozens of studies
      relating to pathophysiology, neuropsychological outcome, and the postconcussion
      syndrome during the past year. Two major reviews have been published. Some of the
      most interesting prospective research has been done with athletes. SUMMARY: The
      cognitive and neurobehavioral sequelae are self-limiting and reasonably
      predictable. Mild traumatic brain injuries are characterized by immediate
      physiological changes conceptualized as a multilayered neurometabolic cascade in
      which affected cells typically recover, although under certain circumstances a
      small number might degenerate and die. The primary pathophysiologies include
      ionic shifts, abnormal energy metabolism, diminished cerebral blood flow, and
      impaired neurotransmission. During the first week after injury the brain
      undergoes a dynamic restorative process. Athletes typically return to pre-injury
      functioning (assessed using symptom ratings or brief neuropsychological measures)
      within 2-14 days. Trauma patients usually take longer to return to their pre
      injury functioning. In these patients recovery can be incomplete and can be
      complicated by preexisting psychiatric or substance abuse problems, poor general
      health, concurrent orthopedic injuries, or comorbid problems (e.g. chronic pain,
      depression, substance abuse, life stress, unemployment, and protracted
      litigation).

PMID- 16639156
TI  - Neuropsychological functioning and alcohol dependence.
AB  - PURPOSE OF REVIEW: Alcohol dependence is a significant challenge to society and
      health-care services. The associated cognitive deficits are thought to affect
      behavioral control, therapy and liability to relapse. The present review
      demonstrates important new findings. RECENT FINDINGS: Recent interest focused on
      compensatory functional circuits, components of executive functioning, externally
      induced attentional biases and the relevance of the cognitive deficits for
      therapy and rehabilitation. SUMMARY: Recent studies found widespread compromised
      fronto-cortico-cerebellar circuits to underlie cognitive deficits. The inclusion
      of cerebellar structures to support functions traditionally associated with
      cortical and even prefrontal structures is important. However, most importantly,
      alcohol-dependent patients use additional and generally higher-order executive
      functions to compensate for deficient task performance. The compensatory
      mechanisms might help to explain close to normal functioning in basic cognitive
      domains enabled by support of executive components. But deficits in executive
      functions themselves might emerge more directly. New approaches concerning
      executive functioning, analyzing functional components of executive tasks, found
      response inhibition and decision-making to be impaired but normal performance in
      simple working memory tasks. Multiple withdrawals have been shown to lead to a
      higher degree of executive deficit. The causing mechanism underlying the
      attentional bias induced by alcohol-related words (stroop effect) is still under
      debate. Correlation of cognitive deficits with therapy outcome turned out to be
      weak. However, important interactions of cognitive deficits with personality,
      therapy-setting and successful coping, together with the finding that cognitive
      performance of alcohol-dependent patients could be enhanced by motivating
      instructions, might open new strategies in treatment planning and cognitive
      rehabilitation.

PMID- 16639157
TI  - Delirium in elderly people: an update.
AB  - PURPOSE OF REVIEW: To review recent studies on epidemiology, diagnosis,
      pathophysiology, treatment and prevention of delirium in elderly people. RECENT
      FINDINGS: There is no evidence that the clinical picture of delirium in elderly
      people differs from that in younger patients, although it may run a more chronic
      course. Diagnosing delirium in demented patients, however, may be difficult due
      to overlap in symptoms of delirium and dementia. Systematic use of screening and
      diagnostic instruments may help to diminish the common underdiagnosis of
      delirium. Delirium is best understood as the result of multiple interacting
      predisposing and precipitating factors. In the elderly, predisposing factors that
      make patients more susceptible for delirium include cognitive dysfunction and
      older age, while important precipitating factors that directly cause delirium are
      any somatic events and the use of anticholinergic drugs. Delirium has a
      significant negative prognostic impact on functional and cognitive outcome, as
      well as on morbidity and mortality. Haloperidol remains the standard treatment
      for delirium, while there is some evidence for the efficacy of risperidone. Other
      atypical antipsychotics, as well as cholinesterase inhibitors, have not yet been
      sufficiently studied. Results of studies on the effectiveness of systematic
      screening of populations at risk and standardized interventions to prevent
      delirium have been inconclusive. SUMMARY: In recent years, the emphasis in the
      approach to delirium has shifted from ad hoc treatment to systematic screening
      and prevention. Interest has been raised in treatment options other than
      haloperidol, such as atypical antipsychotics and procholinergic drugs.

PMID- 16639158
TI  - Update on stroke.
AB  - PURPOSE OF REVIEW: This review highlights the progress achieved in stroke during
      the last year, and emphasizes recent controversies concerning its
      pathophysiology, therapy and secondary complications. RECENT FINDINGS: Studies
      published in 2004 provided new insights into the therapeutic window and ischemic
      penumbra, thrombolysis therapy, uncommon risk factors for stroke, and
      neuropsychological post-stroke complications. Despite the diffusion-perfusion
      mismatch remaining the most widely used technique to identify thresholds for
      ischemic penumbra and irreversible brain tissue damage, new imaging such as
      arterial spin-labeling perfusion and computed tomographic perfusion may define
      this impaired tissue more accurately. New studies assessed the relation of the
      interval from stroke onset to start intravenous thrombolysis treatment (tissue
      plasminogen activator) on favorable 3-month outcome, and on the occurrence of
      clinically relevant parenchymal hemorrhage: the benefit of tissue plasminogen
      activator could extend beyond 3 h, but with a few risks. Systemic inflammations
      and infections have been found to be associated with a substantial increase in
      the risk of developing vascular events, supporting the concept that systemic
      inflammation itself alters the probability of stroke occurrence. Recent
      literature concerning neuropsychological post-stroke complications focused mainly
      on the concept of mixed dementia and confirmed that mood disorders are common
      after stroke, and interfere with its long-term outcome. SUMMARY: Significant
      advances have been made during the last year in determining more accurately the
      therapeutic window, using new strategies and clinical markers. Moreover, new
      light has been thrown on less common stroke risk factors, and neuropsychological
      post-stroke complications.

PMID- 16639159
TI  - Psychiatric aspects of Parkinson's disease.
AB  - PURPOSE OF REVIEW: Recently, there has been much interest and rapid progress in
      understanding the neuropsychiatry of Parkinson's disease. This paper reviews the
      most important papers published during 2004 on dementia and cognitive impairment,
      depression and psychosis in Parkinson's disease. RECENT FINDINGS: Many new
      studies of cognitive impairment and dementia in Parkinson's disease have been
      published during 2004. Cognitive impairment has been demonstrated even during the
      first 1-2 years after onset of disease. Whereas executive and attentional
      impairment is typical, learning deficits occur early in some patients. Both
      functional and structural imaging suggest that in addition to fronto-subcortical
      deficits, temporal and parietal changes occur early as well. In the first large
      placebo-controlled trial, the cholinesterase inhibitor rivastigmine improved
      cognition, daily functioning and psychiatric symptoms without worsening of
      parkinsonism. The frequency and characteristics of depression, anxiety and
      hallucinations have been explored in several studies. Unfortunately, there is
      still little scientific evidence available to guide the treatment of these
      important aspects of Parkinson's disease, and adequately designed clinical trials
      are needed. Although subthalamic stimulation, in addition to improvement of
      movement, is frequently associated with some affective and cognitive improvement,
      permanent and significant worsening may occur in some. Future studies should aim
      at identifying at-risk patients, as well as identifying the optimal
      pharmacological and stimulation treatments for individual patients. SUMMARY:
      These findings provide a deeper understanding of the neurobiological substrate of
      cognitive impairment and dementia in Parkinson's disease, and provide new
      information regarding the assessment and management of dementia and other
      neuropsychiatric aspects of Parkinson's disease.

PMID- 16639160
TI  - Bibliography. Current world literature. Addictive disorders.

PMID- 16639162
TI  - Current concepts in schizophrenia research: advancing progress towards
      understanding etiology and new treatments in year 2004.

PMID- 16639163
TI  - Emerging findings in ethics of schizophrenia research.
AB  - PURPOSE OF REVIEW: We review recent publications pertaining to six topics:
      investigators, professional integrity, and sources of potential bias; scientific
      designs; protocol safeguards; influences on research participation decisions and
      perceptions of risk; informed consent--decision-making capacity, appreciation and
      the therapeutic misconception, and voluntarism; and informed consent-
      intervention studies. RECENT FINDINGS: Little empirical work has been conducted
      on investigator training and potential conflicts of interest. Numerous conceptual
      pieces have tackled controversial issues related to study designs, with the
      initial focal point being the ethics of placebo-controlled studies; only a
      handful of reports, however, have empirically addressed these topics. Emerging
      findings pertinent to protocol safeguards in schizophrenia research suggest
      general support by individuals with schizophrenia for a variety of safeguards.
      Recent work on influences on participation decisions suggests that people with
      schizophrenia use fundamentally similar considerations as medically ill people
      and healthy comparison participants--a combination of personal and altruistic
      motives. Much of the data-based literature has focused on informed consent. We
      highlight studies indicating that patients living with schizophrenia show
      heterogeneity in consent-related abilities but may possess key strengths in the
      research situation, not simply greater vulnerability as suggested in the
      historical literature. Furthermore, consent-related abilities appear to be
      enhanced with educational interventions. SUMMARY: Empirical studies focusing on a
      variety of ethically relevant domains in schizophrenia research are needed.
      Future studies should incorporate quantitative and qualitative methods, integrate
      perspectives of stakeholders, and investigate the effects and appropriateness of
      current protocol safeguards.

PMID- 16639164
TI  - Evidence for white matter abnormalities in schizophrenia.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight important recent
      imaging, histological, and genetic findings relevant to white matter
      abnormalities in schizophrenia. It is cast within the context of research
      findings conducted over the last 5 years, where we analyze their importance in
      understanding schizophrenia, as well as discuss future directions for research.
      RECENT FINDINGS: White matter abnormalities have long been hypothesized in
      schizophrenia, although only recently has it become possible to investigate them
      more closely. This has come about as a result of advances in neuroimaging,
      including new imaging techniques sensitive to white matter structure, as well as
      advances in computer science, with new analysis techniques making it possible to
      evaluate several interconnected brain regions at a time. Postmortem studies, with
      advances such as fluoroscopy and electron microscopy, have also led to
      quantifying populations of different brain cells, including myelin-forming
      oligodendrocytes. Moreover, molecular studies enable examination of
      immunoreactivity of proteins that are responsible for building myelin sheaths.
      Additionally, microarray genetic studies allow us to investigate myelin-related
      genes in schizophrenia. Taken together, these technological advances bring us
      closer to understanding white matter pathology in schizophrenia. SUMMARY:
      Advances in new imaging techniques likely account for the renewed interest in
      investigating white matter abnormalities in schizophrenia, with over 30 new
      articles published on this topic in the last 12 months, compared with 11 the year
      before. We review recent imaging, histological, and genetic findings that suggest
      white matter abnormalities in schizophrenia.

PMID- 16639165
TI  - The inheritance of intermediate phenotypes for schizophrenia.
AB  - PURPOSE OF REVIEW: While schizophrenia is substantially heritable, the mode of
      inheritance is complex, involving numerous genes of small effect and a non
      trivial environmental component. The 'endophenotype' approach is an alternative
      method for measuring phenotypic variation that may facilitate the identification
      of susceptibility genes in the context of complexly inherited traits. Here we
      review recent studies applying this method to measures of brain structure,
      physiology, and function in samples of schizophrenia patients and their non-ill
      first-degree relatives (siblings and co-twins). RECENT FINDINGS: The results
      suggest that there are multiple heritable dimensions of central nervous system
      pathology in schizophrenia, including disturbances in the structure and
      functioning of frontal lobe systems involved in working memory and executive
      processes, temporal lobe systems involved in episodic memory, auditory
      perception, and language processing, and cortical and sub-cortical systems
      mediating smooth pursuit eye movements and sensorimotor gating. A number of
      genetic loci that are suspected to play a role in predisposing to schizophrenia,
      including the DISC1, COMT, neuregulin, dysbindin, and alpha-7 nicotinic receptor
      genes, appear to affect quantitative variation on one or more of these
      indicators. SUMMARY: Future work is encouraged to address whether each of these
      neural system dysfunctions are under the influence of a partially distinct set of
      genes, to elucidate the manner in which multiple genes may coalesce in
      determining schizophrenia-promoting dysfunction in each neurobehavioral domain,
      and to clarify the degree of overlap in these quantitative trait loci
      endophenotype relationships with other forms of psychosis, particularly bipolar
      disorder.

PMID- 16639166
TI  - The schizophrenia envirome.
AB  - PURPOSE OF REVIEW: To show which aspects of the environment increase the risk for
      schizophrenia and how they interact with pre-existing liability for psychosis.
      RECENT FINDINGS: Not only does cannabis survive as a risk factor for psychosis,
      but the evidence is showing concrete synergistic effects between cannabis and pre
      existing liability to psychosis. The urban environment is, in terms of
      attributable risk, the most important proxy environmental risk factor. There is
      evidence that it interacts with genetic risk and it has been hypothesized that
      the mechanism involves the cumulative effects of altered social interactions at
      the individual level and possibly also at the level of the wider social
      environment, such as the neighbourhood. Early trauma is another aspect of the
      environment that has recently been linked prospectively to psychosis, and meta
      analytic work demonstrates conclusively that minority status is a risk factor,
      part of which may be mediated by chronic exposure to discrimination. Prenatal
      environmental effects may involve folate or vitamin D deficiency, viral
      infections or adverse effects associated with low or high birth weight. The
      mechanism by which the environment is likely to impact on risk is through
      cognitive and emotional pathways on the one hand, and biological pathways,
      possibly involving dopamine sensitization, on the other. SUMMARY: Several
      synergistic mechanisms involving proxy measures of genes and proxy measures of
      the environment, such as gene-cannabis, gene-urbanicity and gene-stress
      interactions, offer concrete avenues to pursue research that stands a good chance
      of elucidating at least some of the causes of schizophrenia.

PMID- 16639167
TI  - Early detection of schizophrenia.
AB  - PURPOSE OF REVIEW: This article will evaluate the rationale and feasibility of
      detecting psychosis and schizophrenia earlier than is currently the case. RECENT
      FINDINGS: Schizophrenia incidence may vary more than has been believed
      previously. Early detection studies fall into two groups. Firstly, operational
      criteria now exist for prodromal or at risk mental states which predict
      transition to psychosis of 20-40% over 1 year. The first randomized trials of
      antipsychotic drug and psychological interventions aimed at reducing this
      transition rate have shown promising results. Secondly, duration of untreated
      psychosis in the first episode seems genuinely to be associated with clinical
      outcome but how much of the association is truly causal remains disputed.
      SUMMARY: Shortening duration of untreated psychosis by early detection of full
      psychosis appears feasible but its benefits are not yet unequivocally
      demonstrated.

PMID- 16639168
TI  - Early-stage visual processing deficits in schizophrenia.
AB  - PURPOSE OF REVIEW: While cognitive dysfunction including memory and attentional
      deficits are well known in schizophrenia, recent work has also shown basic
      sensory processing deficits. Deficits are particularly prominent in the visual
      system and may be related to cognitive deficits and outcome. This article reviews
      studies of early-stage visual processing in schizophrenia published during the
      past year. These studies reflect the growing interest and importance of sensory
      processing deficits in schizophrenia. RECENT FINDINGS: The visual system is
      divided into magnocellular and parvocellular pathways which project to dorsal and
      ventral visual areas. Recent electrophysiological and behavioral investigations
      have found preferential magnocellular/dorsal stream dysfunction, with some
      deficits in parvocellular function as well. These early-stage deficits appear to
      be related to higher level cognitive, social, and community function. Structural
      studies of occipital cortex and particularly optic radiations provide anatomical
      support for early visual processing dysfunction. SUMMARY: These findings
      highlight the importance of sensory processing deficits, in addition to higher
      cognitive dysfunction, for understanding the pathophysiology of schizophrenia.
      Understanding the nature of sensory processing deficits may provide insight into
      mechanisms of pathology in schizophrenia, such as N-methyl-D-aspartate
      dysfunction or impaired signal amplification, and could lead to treatment
      strategies including sensory processing rehabilitation that may improve outcome.

PMID- 16639169
TI  - Cognitive-behaviour therapy for schizophrenia: a review.
AB  - PURPOSE OF REVIEW: Most studies demonstrating the benefits of cognitive-behaviour
      therapy for schizophrenia were carried out in the 1990s. The majority targeted
      treatment resistant positive symptoms. Recent research is now focussing on the
      impact of cognitive-behaviour therapy on prodromal states, acute schizophrenia,
      negative symptoms, loss of insight and relapse prevention. RECENT FINDINGS: There
      is mounting evidence to suggest that cognitive-behaviour therapy is an effective
      adjunct to antipsychotic medication in the management of positive symptoms of
      acute schizophrenia as well as negative and residual symptoms of chronic
      schizophrenia. The effect size at the end of therapy is strong, with durability
      at short-term follow up. There is also evidence that cognitive-behaviour therapy
      can be combined with family therapy and assertive community treatment programs
      targeted to reduce relapse. Cognitive-behaviour therapy improves the prognosis of
      patients with schizophrenia through improved adherence and symptom management
      leading to reduced relapse. It may prevent transition to psychosis in high-risk
      prodromal states. SUMMARY: In conclusion, recent literature provides fairly
      strong evidence that cognitive-behaviour therapy in addition to antipsychotic
      medication is effective in the management of acute as well as chronic
      schizophrenia, However, despite its proven efficacy, it remains a rare commodity,
      especially outside the United Kingdom.

PMID- 16639170
TI  - Treatment-refractory schizophrenia.
AB  - PURPOSE OF REVIEW: The aim of this article is to critically review the current
      literature on treatment-refractory schizophrenia with an emphasis on emergent
      themes and key findings. RECENT FINDINGS: New information continues to emerge on
      the impact of each second-generation antipsychotic on the treatment-refractory
      patient population and on the traditionally more difficult-to-treat components
      (e.g. cognition, suicidality, violence) of the illness. There are continued
      efforts with pharmacogenetics to predict response and side-effect risk with
      antipsychotic medications. Polypharmacy continues to be a major and poorly
      understood treatment practice. SUMMARY: Our field is advancing the therapeutic
      nuances of therapy with second-generation antipsychotics in treatment-refractory
      schizophrenia. Additionally, there is a growing appreciation of the emergent
      adverse-effect profile of antipsychotic medications and these risk-benefit
      considerations are more pronounced in severely ill patients.

PMID- 16639171
TI  - Disturbances of glucose and lipid metabolism during treatment with new generation
      antipsychotics.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review the recent literature
      about alterations of lipid and glucose metabolism in patients treated with second
      generation antipsychotics. This article also addresses possible underlying
      mechanisms of these changes and discusses ways of preventing these side-effects
      as well as their management. RECENT FINDINGS: There is a considerable number of
      reports on this issue but very few prospective controlled trials dealing with
      this very important subject. This review further focuses on the question of
      whether there is a difference with respect to such alterations between the
      available new generation antipsychotics, depending on their receptor profiles.
      SUMMARY: As adverse metabolic effects have a high impact on the physical health
      of schizophrenia patients as well as on their treatment adherence, this is a
      topic of major clinical relevance, with implications for public health.

PMID- 16639172
TI  - Classical conditioning of endocrine effects.
AB  - PURPOSE OF REVIEW: Classical conditioning is a form of associative learning,
      based on the pioneering work of I. P. Pavlov: due to its association with an
      unconditioned stimulus that induces an unconditioned response, an initially
      neutral stimulus will become a conditioned stimulus evoking a conditioned
      response in the absence of the unconditioned stimulus. One important area for the
      application of conditioning principles is the regulation of physiological systems
      in general, and endocrine responses and its concomitant changes specifically.
      Conditioned endocrine responses were predominantly addressed in animal studies so
      far, mainly examining conditioned insulin production (and blood-glucose change)
      and corticosterone release. RECENT FINDINGS: There are very few studies on
      classical conditioning of endocrine responses in the annual period of this
      review. The advancement, however, is that some are conducted with humans.
      Recently, as a new avenue, hormones and neurotransmitters have been examined as
      mediators of basic conditioning processes. Moreover, there is an increasing
      interest in gender-specific conditioning responses which are influenced by
      gonadal hormones. SUMMARY: Research on classical conditioning demonstrates that
      endocrine systems are adaptable to environmental signals. Likewise, the endocrine
      status of an organism (at least with regard to glucocorticoids and gonadal
      hormones) was shown to modify classically conditioned responses. Partly due to
      the high expenditure of conducting conditioning experiments, the quantity of
      studies is limited, but there is a need to extend this research to humans. In
      sum, the application of conditioning paradigms constitutes an important research
      tool for behavioral medicine as well as psychiatry to examine brain-behavior
      relationships.

PMID- 16639174
TI  - Bibliography. Current world literature. Schizophrenia.

PMID- 16639173
TI  - Exercise and well-being: a review of mental and physical health benefits
      associated with physical activity.
AB  - PURPOSE OF REVIEW: This review highlights recent work evaluating the relationship
      between exercise, physical activity and physical and mental health. Both cross
      sectional and longitudinal studies, as well as randomized clinical trials, are
      included. Special attention is given to physical conditions, including obesity,
      cancer, cardiovascular disease and sexual dysfunction. Furthermore, studies
      relating physical activity to depression and other mood states are reviewed. The
      studies include diverse ethnic populations, including men and women, as well as
      several age groups (e.g. adolescents, middle-aged and older adults). RECENT
      FINDINGS: Results of the studies continue to support a growing literature
      suggesting that exercise, physical activity and physical-activity interventions
      have beneficial effects across several physical and mental-health outcomes.
      Generally, participants engaging in regular physical activity display more
      desirable health outcomes across a variety of physical conditions. Similarly,
      participants in randomized clinical trials of physical-activity interventions
      show better health outcomes, including better general and health-related quality
      of life, better functional capacity and better mood states. SUMMARY: The studies
      have several implications for clinical practice and research. Most work suggests
      that exercise and physical activity are associated with better quality of life
      and health outcomes. Therefore, assessment and promotion of exercise and physical
      activity may be beneficial in achieving desired benefits across several
      populations. Several limitations were noted, particularly in research involving
      randomized clinical trials. These trials tend to involve limited sample sizes
      with short follow-up periods, thus limiting the clinical implications of the
      benefits associated with physical activity.

PMID- 16639176
TI  - Atypical depression: Australian and US studies in accord.
AB  - PURPOSE OF REVIEW: A 2004 review of 'atypical depression' in Current Opinion in
      Psychiatry could be read as more reifying the Columbian and DSM-IV concept rather
      than considering an alternative model that has been supported by independent
      studies undertaken in Australia and North America. Additional analyses of the
      Australian data set are reported to examine inter-study agreement further and to
      consider the implications. RECENT FINDINGS: Both studies recruited patients
      meeting criteria for a major depressive episode, and then contrasted patients
      meeting or not meeting DSM-IV criteria for definite atypical depression. In both
      studies, those with atypical depression were comparable in terms of female
      preponderance, age, age at first episode and depression severity, but developed
      earlier and more persistent episodes, showed a slight female preponderance, and
      were more likely to meet criteria for panic disorder, social phobia and
      hypochondriasis, and of avoidant and dependent personality styles. In both, there
      was a lack of evidence suggesting that atypical depression differs in severity,
      in being clearly less likely to have certain 'endogeneity' symptoms, or in being
      more likely to be associated with bipolar disorder, while neither the centrality
      of mood reactivity nor interdependence of symptoms could be demonstrated.
      SUMMARY: Findings from both studies challenge the view that atypical depression
      is an entity and the current model of its constituent features. Both found
      support for primacy of personality style (rather than mood reactivity) and for
      certain expressions of anxiety. Both effectively argue for and assist shaping of
      a revisionist model for conceptualizing atypical depression as a syndrome or
      spectrum disorder.

PMID- 16639177
TI  - Current status of virtual reality exposure therapy in anxiety disorders:
      editorial review.
AB  - PURPOSE OF REVIEW: In recent years, a considerable number of publications have
      appeared on different aspects of virtual reality exposure therapy in the
      treatment of anxiety disorders. The purpose of the present article is to review
      the evidence that has emerged to support the potential of this therapy in the
      treatment of anxiety disorders. RECENT FINDINGS: Case histories and open
      comparative studies, as well as randomized controlled studies, have been
      published on the use of virtual reality exposure therapy in the treatment of
      anxiety disorders. Most studies in the field have been on specific phobias, in
      particular on fear of flying, acrophobia, fear of driving, claustrophobia and
      fear of spiders. In addition, several studies have been published on the use of
      virtual reality exposure therapy for social anxiety disorders, posttraumatic
      stress disorder and panic disorder with or without agoraphobia. SUMMARY: Recent
      studies provide evidence that virtual reality exposure therapy is a promising
      tool for the treatment of several anxiety disorders.

PMID- 16639178
TI  - Child and adolescent antecedents of adult mood disorders.
AB  - PURPOSE OF REVIEW: Developmental information such as childhood risk factors and
      childhood precursors of adult mood disorders may have implications for etiologic
      theory, clinical practice and preventive intervention. From a developmental point
      of view, mood disorders are of particular interest because of the complex
      interplay of psychological, social and biological components across time.
      Identifying different developmental trajectories of mood disorders may yield
      insights that are relevant to the etiology. RECENT FINDINGS: Findings demonstrate
      a clear association between early mood problems and onset of mood disorders in
      adult life. Childhood environmental risks are associated with increased risk of
      depression in adulthood. There is a lack of studies that have tested the role of
      gene-environment correlation and the role of gene-environment interaction in the
      development of depression from childhood into adulthood. A promising line of
      research comes from studies looking into the biological modifications of the
      developing brain as a result of early adverse experiences, especially alterations
      in the corticotropin-releasing factor system, which may lead to increased
      responsiveness to stress. SUMMARY: To better understand the complex interplay
      between nature and nurture in the development of mood disorders in adults, future
      studies should ideally consider well measured risk environments in genetic
      sensitive designs. It is equally important that future studies should also
      consider both age differences in causal processes and gender differences in
      effects. Such an approach calls for research in which (molecular) genetic and
      psychosocial research is well integrated in prospective epidemiological
      strategies.

PMID- 16639179
TI  - Are the SSRIs and atypical antidepressants safe and effective for children and
      adolescents?
AB  - PURPOSE OF REVIEW: This article summarizes recent developments in the use of
      selective serotonin reuptake inhibitors and atypical antidepressants to treat
      children and adolescents with depression at a time when their use in this context
      has generated considerable controversy and confusion for clinicians, patients and
      their families. Recent reports and recommendations from drug regulators in the UK
      and the US are discussed, alongside other reviews and recently published
      randomized controlled trials. RECENT FINDINGS: It is now widely accepted that
      these drugs increase the risk of suicide-related behaviours and although recently
      published trials have been more positive, a meta-analysis of published and
      unpublished trials has cast doubt about efficacy. The evidence for publication
      bias in the studies considered is also raised and the implications discussed.
      There is some evidence, however, that the combination of psychological treatment
      with fluoxetine may be both effective and protective against the increased risk
      of suicide-related behaviours, although problems over blinding suggest further
      research is needed to clarify this potentially positive combination treatment.
      SUMMARY: Current evidence supports the conclusions of the UK drug regulator in
      warning against the use of all the newer antidepressants except fluoxetine in
      this age group, and alternative therapies should be sought in the first instance.
      Caution is needed in interpreting drug company sponsored trials given the
      evidence of selective reporting and publication bias. Combining fluoxetine with a
      psychological treatment such as cognitive-behavioural therapy is also worth
      considering.

PMID- 16639180
TI  - Managing mood disorders and comorbid personality disorders.
AB  - PURPOSE OF REVIEW: To examine the influence of personality disorder comorbidity
      on the general treatment of mood disorders. RECENT FINDINGS: Personality
      disorders generally have a negative influence on outcome of mood disorders, both
      unipolar and bipolar. When the personality features are addressed, however, the
      outcome is less negative. Recent studies suggest a special role for psychological
      and educational therapies in the treatment of these comorbid disorders. SUMMARY:
      The assessment of, and attention to, the management of personality disorder as
      well as concurrent mood disorder may improve outcome.

PMID- 16639181
TI  - Pharmacogenetics in mood disorder.
AB  - PURPOSE OF REVIEW: Not all patients with mood disorder respond well to drug
      treatment. Emerging data suggest that genetic mechanisms could be involved. We
      searched the literature database and highlighted recent molecular genetic studies
      pertaining to drug response in mood disorders. RECENT FINDINGS: Recent
      pharmacogenetic studies in mood disorders have reported generally positive
      findings supporting the view that genotyping may improve the confidence of
      prospectively identifying treatment response and adverse outcomes. SUMMARY: The
      evidence documenting genotype-based response to drug treatment is rapidly
      expanding. Genes encoding target receptors and signal transduction systems may
      predict the efficacy of drug therapy in mood disorders. Additional predictors of
      treatment response in bipolar disorder may include the immediate early genes,
      mitochondrial genes and epigenetic mechanisms, although some of these studies are
      still preliminary.

PMID- 16639182
TI  - A dimensional model of personality disorder.
AB  - PURPOSE OF REVIEW: Research planning work-groups sponsored by the American
      Psychiatric Association have called for the development of a dimensional model of
      personality disorder for a future edition of the diagnostic manual. RECENT
      FINDINGS: This paper provides a brief summary of current research relevant to the
      proposal to integrate basic science research on the five-factor model of general
      personality structure with the diagnosis of personality disorders. Recent studies
      and the particular advantages of a five-factor model of personality disorder are
      presented. SUMMARY: Future editions of diagnostic manuals will move toward a more
      dimensional model of personality disorder classification. Clinicians will benefit
      from a greater familiarity with this approach to diagnosis, as researchers
      continue to develop their validity and clinical utility.

PMID- 16639183
TI  - The treatment of panic disorder.
AB  - PURPOSE OF REVIEW: The aim of this article is to provide an updated review of
      studies and recommendations published from August 2003 to August 2004 on the
      treatment of panic disorder. RECENT FINDINGS: Cognitive-behavioral psychotherapy
      remains the treatment of choice for panic disorder. Recent studies confirm
      selective serotonin reuptake inhibitors as the first-choice drugs in treating
      panic disorder. Recommendations for (adjunctive) high-potency benzodiazepines
      have been published. Psychoeducation and combined pharmacotherapy/psychotherapy
      improve treatment response. Optimal long-term treatment of panic disorder
      involves adequate medication and duration of treatment, since relapse is
      frequent. SUMMARY: Recent studies confirm that cognitive-behavioral therapy,
      alone or in combination with drug therapy, remains the treatment of choice for
      panic disorder. Long-term treatment is often necessary due to the chronicity of
      the illness.

PMID- 16639184
TI  - Recent developments in research and treatment for social phobia (social anxiety
      disorder).
AB  - PURPOSE OF REVIEW: This review covers three themes of research that brought fresh
      data useful for clinical practice in a handicapping anxiety disorder: social
      phobia. Recent findings deriving from basic biological research, new forms of
      psychological therapies, and recent psychopharmacology controlled trials are
      reviewed. RECENT FINDINGS: The basic neuroimaging research suggests that greater
      activation of the amygdala to novel versus familiar faces may be an underlying
      trait marker for social phobia. Social phobia may represent a phenotype that
      expresses a genetically driven trait of social withdrawal, which may be related
      to infantile inhibited temperament (Kagan's syndrome). The development of virtual
      reality therapy as therapeutic tool for social phobia appeared promising in one
      controlled, but not randomized, study. A controlled study suggests that social
      phobias in children can be effectively treated with cognitive behavioural
      therapy. This represents an extension of the work done with adults. Venlafaxine
      appears an effective short-term treatment for social anxiety disorder in two
      controlled studies. A new compound, pregabalin, appeared clearly effective in a
      positive controlled study. This trial marks the advent of a new pharmacological
      lineage for social phobia. Both venlafaxine and pregabalin, however, have been
      studied in short-term studies. Longer follow-up and relapse prevention studies
      are warranted. SUMMARY: Neuroimaging research points to a temperamental basis for
      social phobia. Virtual reality therapy is an emerging tool to carry out exposure
      treatment. Group cognitive behavioural therapy can be extended successfully to
      children. Venlafaxine and pregabalin have a proven short-term effectiveness in
      social phobia.

PMID- 16639185
TI  - New fields of research in posttraumatic stress disorder: brain imaging.
AB  - PURPOSE OF REVIEW: This paper reviews the most recent literature on brain imaging
      research in posttraumatic stress disorder. Neuroimagery identifies several
      cerebral modifications occurring after a significant psychological trauma, and it
      contributes to a better understanding of the pathophysiology of posttraumatic
      stress disorder. A systematic search of the literature in English, French, German
      and Dutch from January 2003 to August 2004 was performed on MEDLINE. References
      cited in all trials were searched iteratively to identify missing studies. RECENT
      FINDINGS: There appears to be a consensus in brain imaging findings concerning
      posttraumatic stress disorder: a diminished volume of the hippocampus uni- or
      bilateral (on the structural level) and a hyper-reactivity in the amygdala, with
      a lowered activation in the anterior cingular cortex (at the functional level).
      These findings are in agreement with several neurological and psychological
      studies suggesting that hyper-reactivity in the amygdala corresponds to a
      constellation of symptoms of anxiety in posttraumatic stress disorder, while the
      lowered activation of the prefrontal and the anterior cingular cortex could
      reflect slower extinction of a conditioned emotional response. SUMMARY: These
      neuroimaging findings could contribute to a better understanding of posttraumatic
      stress disorder. The integration of neurobiological, social and psychological
      findings may lead to an improved approach to the pathophysiology of posttraumatic
      stress disorder and perhaps to the development of new pharmacological treatment.
      Future studies could integrate the disparate findings among numerous biological
      systems and propose an integrative structural, functional and endocrinological
      model.

PMID- 16639186
TI  - Rethinking somatoform disorders.
AB  - PURPOSE OF REVIEW: From the very moment of their inclusion in contemporary
      classification systems in psychiatry, the concept of somatization and diagnostic
      categories of somatoform disorders became a matter of controversy that created an
      ongoing debate about their validity, reliability and applicability in clinical
      and research settings. The aim of this review is to provide an insight into the
      current theoretical, research and clinical dilemmas in the area of somatoform
      disorders and to illustrate them with brief summaries of scientific papers
      recently published in this field. RECENT FINDINGS: In the period covered by this
      review, the most valuable scientific contributions to the current state of
      knowledge on somatoform disorders were (surprisingly numerous) review papers
      produced by the leading experts in this field. These comprehensive and critical
      meta-analyses covered historical, conceptual, epidemiological and cross-cultural
      aspects of somatoform disorders. Another and a relatively smaller group of
      recently published papers reported on some novel treatment strategies for
      patients with specific somatoform disorders, their service utilization and health
      care-related costs. SUMMARY: If one were to find a common denominator of the
      papers covered by this review, it is a general agreement amongst their authors
      that the current concepts of somatization and somatoform disorders have serious
      theoretical and practical limitations in both research and clinical settings.
      They suggest that the time has come to seriously rethink these concepts so as to
      find better nosological solutions for the forthcoming revisions of classification
      systems in psychiatry and medicine.

PMID- 16639187
TI  - The use of the Internet in the treatment of anxiety disorders.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the emerging literature
      on the use of the Internet in the treatment of anxiety disorders. The questions
      asked are: (1) are Internet-delivered treatments for anxiety disorders supported
      by the research literature? (2) what is the quality of the evidence as it stands?
      (3) is there any evidence to suggest that Internet interventions can be harmful?
      RECENT FINDINGS: Recent and ongoing trials on panic disorder show that Internet
      based self-help with minimal therapist contact is a promising approach in the
      treatment of panic disorder. However, trials have been small and there is a need
      for large-scale trials and studies conducted in psychiatric settings as most
      studies have recruited patients via advertisement. There is no evidence in the
      literature that Internet intervention is harmful, but most likely a stepped-care
      approach would be feasible to handle cases who fail to respond. SUMMARY: Internet
      delivered interventions for anxiety disorders, and in particular panic disorder,
      are promising. There is however a need for further research and evaluation and
      there is also a need to find a proper place for such interventions in the
      clinical management of anxiety disorders, preferably using a stepped-care
      approach.

PMID- 16639188
TI  - Bibliography. Current world literature. Mood disorders.

PMID- 16639189
TI  - The teaching of basic sciences in medical schools.

PMID- 16639190
TI  - Hello, stranger: building a healing narrative that includes everyone.
AB  - The authors use the concept of "samaritan medicine" to tie together papers by
      Klitzman, by Wear and colleagues, and by Branch appearing in this issue of
      Academic Medicine on the physician-patient relationship. Practicing physicians
      and trainees alike must confront the challenge of acknowledging and connecting to
      otherness or difference in patients and in themselves, and practice based in
      "samaritan medicine" can help to bridge the gaps between self and other. The
      authors present three vignettes that highlight physicians' and patients'
      differing perspectives on the stories in which they are mutually involved. The
      authors then suggest three approaches that operate at the organization as well as
      the individual level and that speak to establishing and sustaining health
      supporting relationships between patients and doctors: video review and replay,
      Appreciative Inquiry, and self-disclosure. The aim of such approaches is that
      physicians and physician-trainees be able to ask-and answer-questions about the
      "narratives" they are enacting, such as "In this story, where am I? Where is the
      other? Where is the common good? What, then, should I do?" in order that they may
      develop a robust appreciation of patient interactions and understanding of self
      that fosters the practice of "samaritan medicine."

PMID- 16639192
TI  - Improving oversight of the graduate medical education enterprise: one
      institution's strategies and tools.
AB  - Accreditation organizations, financial stakeholders, legal systems, and
      regulatory agencies have increased the need for accountability in educational
      processes and curricular outcomes of graduate medical education. This demand for
      greater programmatic monitoring has placed pressure on institutions with graduate
      medical education (GME) programs to develop greater oversight of these programs.
      Meeting these challenges requires development of new GME management strategies
      and tools for institutional GME administrators to scrutinize programs, while
      still allowing these programs the autonomy to develop and implement educational
      methods to meet their unique training needs. At the Medical University of South
      Carolina (MUSC), senior administrators in the college of medicine felt electronic
      information management was a critical strategy for success and thus proceeded to
      carefully select an electronic residency management system (ERMS) to provide
      functionality for both individual programs and the GME enterprise as a whole.
      Initial plans in 2002 for a phased deployment had to be changed to a much more
      rapid deployment due to regulatory issues. Extensive communication and
      cooperation among MUSC's GME leaders resulted in a successful deployment in 2003.
      Evaluation completion rates have substantially improved, duty hours are carefully
      monitored, patient safety has improved through more careful oversight of
      residents' procedural privileges, regulators have been pleased, and central GME
      administrative visibility of program performance has dramatically improved. The
      system is now being expanded to MUSC's medical school and other health
      professions colleges. The authors discuss lessons learned and opportunities and
      challenges ahead, which include improving tracking of development of procedural
      competency, establishing and monitoring program performance standards, and
      integrating the ERMS with GME reimbursement systems.

PMID- 16639194
TI  - Competencies, essential training, and resources viewed by designated
      institutional officials as important to the position in graduate medical
      education.
AB  - PURPOSE: In 1998, the Accreditation Council for Graduate Medical Education
      (ACGME) added the stipulation that each institution providing graduate medical
      education (GME) have a Designated Institutional Official (DIO). The authors
      conducted this study via a cross-sectional survey designed to provide descriptive
      data on the beliefs held by DIOs regarding required competencies, training and
      experience, and desired resources for the position. METHOD: The authors collected
      data between January 2004 and May 2004 using a multistep process that included a
      prenotice letter; a survey, cover letter, and stamped return envelope; a thank
      you/reminder postcard; and a replacement survey with new cover letter and stamped
      return envelope. Data were summarized using descriptive statistics. RESULTS:
      Completed surveys were received from 243 of 363 DIOs (66.9%). Eighty-two percent
      indicated that DIOs should have specified minimum experience or training
      requirements. Ten competency items were viewed as essential by greater than 50%
      of respondents, with five items endorsed by over 95% of respondents:
      professionalism, verbal communication skills, interpersonal skills, leadership
      skills, and written communications skills. The percentage of responding DIOs who
      indicated they would be very likely to use resources were as follows: templates
      for GME policies, contracts, and affiliation agreements (83.1%); DIO-specific
      training (58.0%); data on DIO demographics (53.9%); DIO job description templates
      (46.9%); a clear description of DIO versus program director responsibilities
      (46.1%); and a DIO certification program (32.1%). CONCLUSIONS: Designated
      Institutional Officials supported the idea that there should be minimum
      experience and requirements and demonstrated remarkable consistency in endorsing
      essential competencies for the position. DIOs, their respective institutions, the
      ACGME, and other GME organizations and associations may use the data from this
      study to develop the role further.

PMID- 16639195
TI  - Washington University School of Medicine.

PMID- 16639196
TI  - Improving resource utilization in a teaching hospital: development of a
      nonteaching service for chest pain admissions.
AB  - PURPOSE: Exclusion of acute coronary syndrome frequently prompts a brief hospital
      admission for a large proportion of patients presenting to the emergency
      department with chest pain. At hospitals with residency programs, the volume of
      such patients creates pressures on these programs because of the limit on the
      number of patients a resident can accept in a given period. These restrictions
      have been instituted by the Accreditation Council for Graduate Medical Education
      (ACGME). The authors hypothesized that a nonteaching service designed to identify
      and admit low-risk chest pain patients should reduce those pressures. METHOD: A
      hospitalist-directed nonteaching service (NTS) was created to admit low-risk
      chest pain patients at the Hospital of the University of Pennsylvania. Patients'
      admission service was based upon the thrombolysis in myocardial infarction (TIMI)
      risk score. From September 2003 to June 2004, patients (n = 113) with scores of 0
      or 1 (showing low risk) were admitted to the NTS. Simultaneously, a similar group
      of low-risk chest pain patients (n = 205) were admitted to a traditional internal
      medicine resident-based service (RBS). RESULTS: The NTS patients had a lower
      median length of stay (23 hours versus 33 hours; p < .0001) and lower median
      hospital charges ($8,545 versus $14,150; p < .0001) when compared with the low
      risk patients on the RBS. CONCLUSIONS: The development of an NTS for chest pain
      admissions can assist residency programs in their efforts to meet the ACGME
      program requirements. The TIMI risk score can be used as a tool to assist in the
      identification of low-risk chest pain patients.

PMID- 16639197
TI  - Combating the stress of residency: one school's approach.
AB  - Residency is a time of stress and turmoil for many residents. The stresses are
      varied and great, often involving both personal and professional issues. One
      institutional mechanism that has been shown to help residents cope with stress is
      the use of residents' wellness, or assistance, programs. The University of South
      Florida (USF) College of Medicine developed the USF Residency Assistance Program
      (RAP) in 1997, modeled after business employee assistance programs but tailored
      to enhance the well-being of residents. The program was developed in an
      organized, thoughtful manner starting with a Request for Proposals to all local
      employee assistance programs and the selection of one of these to run the
      program. The RAP is broad-based, readily available, easily accessible, totally
      voluntary and confidential, and not reportable to the state board of medicine. It
      is well integrated into all residency programs and has had excellent acceptance
      from the administration; information about access to the RAP is available to all
      residents through multiple venues. The cost is minimal, at only seven cents a day
      per resident. The authors present data from the eight years the RAP has been
      operating, including information on program use, referral rates, acceptance, and
      types of problems encountered. One suicide occurred during this time period, and
      the RAP provided a significant role in grief counseling. Assistance programs are
      critical to the well-being of residents. The USF program presents a model that
      can be used by other programs around the country.

PMID- 16639198
TI  - Training experiences of U.S. combined internal medicine and pediatrics residents.
AB  - PURPOSE: To investigate the demographics and training experiences of internal
      medicine and pediatrics (med-peds) physicians. METHOD: A cross-sectional survey
      addressing demographics, training experiences, and career plans of fourth-year
      residents graduating from combined internal medicine and pediatrics programs that
      were identified in the American Academy of Pediatrics database was initiated in
      May 2003. Questionnaires were mailed up to four times to nonresponders through
      August 2003. RESULTS: Valid responses were received from 212 of the 340
      graduating residents (62% response rate). The majority (186/208 [89%]) reported
      that they would choose med-peds training again. Career planning (135/210 [64%]),
      office management (173/212 [82%]), and outpatient procedures (155/211 [73%]) were
      the only areas where the majority desired more training. Neonatal intensive care
      training was the only topic area that the majority of residents (142/212 [67%])
      reported could have been carried out in less time. Nearly all residents (183/196
      [93%]) planned to care for children and adults. Residents' self-assessment of
      their preparation was good to excellent for evidence-based medicine (192/210
      [91%]), caring for patients with special health care needs (179/209 [86%]), and
      use of information technology (169/208 [81%]). Residents felt equally well
      prepared for postgraduate activities in internal medicine and pediatrics primary
      care (170/212 [80%] versus 163/211 [77%], p = .305, NS) and internal medicine and
      pediatric fellowships (186/207 [90%] versus 181/208 [87%], p = .058, NS). Only
      112 of 209 residents (54%) felt their preparation for research was good to
      excellent. CONCLUSIONS: The study findings suggest that med-peds residents are
      satisfied with their decision to train in med-peds and with their level of
      preparation. They feel equally well prepared to care for adults and children, and
      well prepared to care for patients that may transition to adulthood with complex
      needs, to assess evidence, and to use information technology.

PMID- 16639199
TI  - Improving education on doctor-patient relationships and communication: lessons
      from doctors who become patients.
AB  - PURPOSE: Medical education faces challenges in training empathetic doctors who
      have good patient communication skills. The author aimed to understand insights
      that doctors who become patients may gain concerning ways to improve doctor
      patient relationships and communication in order to improve medical education.
      METHOD: From 1999 to 2002, based in New York, the author conducted two in-depth,
      semistructured, two-hour interviews with each of 50 doctors who had serious
      illnesses concerning their overlapping experiences of being health care workers
      and becoming patients. Interviews examined their views about these issues and how
      their perspectives changed as a result of patienthood. RESULTS: These doctor
      patients questioned whether and to what degree empathy could be taught, but
      nonetheless provided several techniques for improving communication with patients
      related to process and content of care. Processes included charting at the
      bedside rather than at the nursing station, acknowledging having kept patients
      waiting, and increasing awareness of nonverbal aspects of care. Content issues
      included communicating directly about taboo topics and being more sensitive in
      discussing "bad news," adherence, and nonmedical concerns. CONCLUSIONS: Doctors
      reported increased sensitivity to patients' experiences and empathy in doctor
      patient communication. These findings can help in teaching doctors to see more
      clearly that their specific point of view differs from that of patients, and can
      be limiting. This study also sheds light on the wide separation between
      intellectual and experiential learning, which needs to be addressed further in
      medical education and research.

PMID- 16639201
TI  - Making fun of patients: medical students' perceptions and use of derogatory and
      cynical humor in clinical settings.
AB  - PURPOSE: It has long been known that medical students become more cynical as they
      move through their training, and at times even exhibit "ethical erosion." This
      study examines one dimension of this phenomenon: how medical students perceive
      and use derogatory and cynical humor directed at patients. METHOD: The authors
      conducted five voluntary focus groups over a three-month period with 58 third-
      and fourth-year medical students at the Northeastern Ohio Universities College of
      Medicine in 2005. After transcribing the taped interviews, the authors analyzed
      the data using qualitative methods and identified themes found across groups.
      RESULTS: The categories that emerged from the data were (1) categories of
      patients who are objects of humor, including those deemed "fair game" due to
      obesity or other conditions perceived as preventable or self-inflicted; (2)
      locations for humor; (3) the "humor game," including student, resident, and
      faculty interaction and initiation of humor; (4) not-funny humor; and (5) motives
      for humor, including coping and stress relief. CONCLUSIONS: The authors offer
      recommendations for addressing the use of derogatory humor directed at patients
      that include a more critical, open discussion of these attitudes and behaviors
      with medical students, residents, and attending physicians, and more vigorous
      attention to faculty development for residents.

PMID- 16639202
TI  - A true group effort.

PMID- 16639203
TI  - Viewpoint: teaching respect for patients.
AB  - Respect is a core value of medical professionalism. Respect for patients often
      manifests itself as an attitude, of which the physician is only partially self
      aware. To teach respect means bringing it fully into consciousness. Physicians
      then should strive to make respect an inner quality, beyond being a behavior. The
      author illustrates the depth of feeling involved in respecting another person by
      citing passages from Let Us Now Praise Famous Men, James Agee's classic book that
      describes Depression-era tenant farmers. However, major barriers inhibit teaching
      of respect in clinical settings. The author proposes that synergies can be
      achieved that overcome the barriers by combining the effective modeling of
      respect in bedside teaching with formal teaching exercises involving patients and
      deep critical reflection using narratives wherein learners describe their
      experiences in patient care.

PMID- 16639205
TI  - The use of Spanish by medical students and residents at one university hospital.
AB  - PURPOSE: To describe how medical trainees report communication with Spanish
      speaking patients, and to assess trainees' desire to improve their language
      skills and have those skills formally evaluated. METHOD: A questionnaire was
      mailed to all fourth-year medical students and non-first-year residents in family
      practice, pediatrics, medicine, medicine-pediatrics, emergency medicine, and
      obstetrics-gynecology at the University of Rochester School of Medicine and
      Dentistry in 2004 (N = 263). RESULTS: The response rate was 92% (241/263). Each
      respondent had at least one year of clinical experience at the hospital. Of the
      83% (199/241) who reported less than conversational Spanish language skills, 53%
      had taken a history and/or provided medical advice directly to Spanish-speaking
      patients without any form of interpretation. When an interpreter was used,
      professional interpretation services were used less frequently than other forms
      of interpretation (42% versus 58%, p < .05). Analyses were performed on the 68%
      (164/241) who reported having at least rudimentary Spanish skills: 85% reported
      that they would probably or definitely participate in further individual language
      training, 70% expressed at least possible willingness to have their Spanish
      formally evaluated, and 80% predicted that it is at least possible that they will
      use their Spanish as attending physicians. CONCLUSIONS: At the time of this
      study, this hospital's medical students and residents from multiple specialties
      used inadequate Spanish language skills to provide direct medical care despite
      the availability of professional interpretation services. Most of these trainees
      were motivated to improve their Spanish and would welcome evaluation of their
      language skills.

PMID- 16639206
TI  - Medicine and the arts. Three Elling Solheim poems translated by Alison Arderne
      Philip. Commentary.

PMID- 16639208
TI  - What do medical schools teach about women's health and gender differences?
AB  - PURPOSE: To examine the curricula of U.S. medical schools to assess the inclusion
      of women's health and gender-specific information and identify institutional
      characteristics associated with this content. METHOD: Using data from the
      Association of American Medical Colleges' Curriculum Management and Information
      Tool (CurrMIT), in November 2003 to February 2004 the authors performed a
      curriculum search of schools that entered course/clerkships in CurrMIT to
      identify interdisciplinary women's health or gender-specific courses/clerkships.
      A subset of schools that entered comprehensive information in CurrMIT was
      searched for a specified list of women's health topics and or gender-specific
      content on any topic. Statistical analyses were performed to assess the
      relationship between frequency of topics and school characteristics. RESULTS: The
      authors identified 95 schools that entered related courses/clerkships. Ten
      courses/clerkships at nine schools met criteria for an interdisciplinary women's
      health course/clerkship. In the subset of 60 schools with comprehensive CurrMIT
      information, 18 specified women's health topics were identified, as well as 24
      topics on gender-specific content, for a total of 42 topics. The number of topics
      taught ranged from zero to 26 (mean = 11). More than 50% of these schools taught
      11 of the 18 specified topics, while fewer than 30% included gender-specific
      topics. There was no association in bivariate analysis between the mean number of
      topics taught and schools' characteristics; however, a women's health program (p=
      .01) and female dean (p= .06) were positively associated in a regression model.
      CONCLUSIONS: Few schools offer interdisciplinary women's health
      courses/clerkships or include gender-specific information in their curricula. A
      designated women's health program may increase this content in schools'
      curricula.

PMID- 16639209
TI  - Bridge over troubled water.

PMID- 16639210
TI  - Using an outcomes-logic-model approach to evaluate a faculty development program
      for medical educators.
AB  - PURPOSE: This study used an outcomes-logic-model approach to examine the impact
      of participating in a nontraditional professional development program. Building
      and using a logic model provides a structure for the program to examine the
      degree that the desired learner outcomes, the program delivery methods, and the
      measurement approaches are aligned. METHOD: Structured telephone interviews were
      conducted in 2001 with 16 Harvard Medical School (HMS) participants in the
      Harvard Macy Program for Physician Educators (HM-PE): five who completed the
      program in 1998, five in 1999, and six in 2000. Interviews were also conducted
      with four Faculty Scholars, alumni of the HM-PE program who taught in subsequent
      programs. In 2004, online questionnaires were sent to the 16 participants and
      four Faculty Scholars. Immediate outcomes, such as greater use of active learning
      principles, and intermediate outcomes, such as commitment to medical education,
      were examined. RESULTS: Of those interviewed in 2001, 80% responded to the 2004
      online questionnaire. Thirteen of 16 (81%) HMS respondents reported increased
      knowledge about and confidence using learner-center teaching methods; 10 of 16
      (63%) said they gave fewer lectures and added alternative educational methods.
      Thirteen of 16 (81%) reported a stronger commitment to the field of medical
      education: almost one third felt the HM-PE program was a turning point in their
      careers. CONCLUSIONS: The outcomes logic model provided data to judge how well
      the program mission and plan were implemented, and whether outcomes had been
      attained.

PMID- 16639211
TI  - The reading habits of medicine clerks at one medical school: frequency,
      usefulness, and difficulties.
AB  - PURPOSE: To describe the reading habits of medicine clerks, which previously have
      not been well described. Understanding issues related to student reading habits
      may provide insights and opportunities for medical educators to develop methods
      to improve clerks' clinical clerkship experiences and their information literacy
      skills. METHOD: The authors administered an 18-item survey tool to 120 students
      on their first inpatient internal medicine clerkships at the Johns Hopkins
      University School of Medicine in 2002-03. The questionnaire focused on issues
      related to what and how often they read during their basic medicine clerkship.
      Data were explored mainly with descriptive statistics. RESULTS: One hundred
      twelve of 120 (93%) medicine clerks completed the survey. Clerks reported reading
      for an average of 10.8 (SD 5.6) hours per week (median ten hours per week, range
      one to 30 hours per week). The most commonly used and useful reading sources were
      UpToDate and test preparation textbooks. Approximately 30% of students reported
      substantial problems in reading about their patients. Limited data suggest that
      reading habits and learning methods vary by year of medical school. Clerks are
      given disparate advice on appropriate reading sources to consult by attending
      physicians, resident physicians, and fellow students. CONCLUSIONS: Students spend
      significant amounts of time reading online sources during their medicine
      clerkship, especially UpToDate. Medical educators should become familiar with
      these sources and contribute to maximizing their effectiveness for students.
      Additional research focused on understanding how students build skills in
      information literacy and how educational programs can facilitate the development
      of those skills is needed.

PMID- 16639217
TI  - New 2006 wound care-related HCPCS codes.

PMID- 16639218
TI  - The evolution of support surfaces.

PMID- 16639219
TI  - Documentation: a vital link to nutritional care.

PMID- 16639220
TI  - What is the best method for assessing the rate of wound healing? A comparison of
      3 mathematical formulas.
AB  - OBJECTIVE: To identify and evaluate current mathematical formulas used to assess
      the rate of wound healing. DATA SOURCES: MEDLINE, CINAHL, and Cochrane Systematic
      Review databases, from 1965 to 2004. STUDY SELECTION: Papers selected for the
      study met the following inclusion criteria: (1) participants had chronic venous,
      neuropathic, pressure, or ischemic wounds; (2) the wounds were objectively
      measured; and (3) the investigators described and used an objective measurement
      of wound healing rate, either as an absolute reduction in area over time, a
      percentage change, or a linear advancement of wound edge. Papers were excluded if
      they were (1) not written in English, (2) duplicated from other sources, or (3)
      unpublished. CONCLUSIONS: In clinical trials, measurement of the rate of wound
      healing over time by using the equation for the linear advancement of wound
      margins toward the center of the wound controls for confounding introduced by
      differing baseline ulcer sizes and shapes. Use of this assessment method after 4
      weeks of healing may prove to be of value in predicting time to complete healing.
      Further research is required to develop standard healing rates for wounds of
      different etiologies.

PMID- 16639221
TI  - When the goal is palliative care.
AB  - OBJECTIVE: An analysis of the literature regarding palliative care of patients
      with wounds. DATA SOURCES: Health care literature, including national and
      international reports, focusing on enhancing quality of life for individuals with
      wounds who are receiving palliative care. CONCLUSION: The literature on
      palliative care of patients with wounds is limited. Integration of palliative
      care concepts and chronic wound management is challenging; however, palliative
      care, which focuses on comfort and symptom management for quality of life, can
      provide the best quality care within the parameters of disease and individual
      patient wishes.

PMID- 16639222
TI  - Wound documentation: managing risk.
AB  - PURPOSE: To provide the physician and registered professional nurse with an
      understanding of consistent wound documentation and the potential for legal
      issues to arise. TARGET AUDIENCE: This continuing education activity is intended
      for physicians and nurses with an interest in better understanding and improving
      policies and procedures related to wound documentation. OBJECTIVES: After reading
      the article and taking the test, the participant should be able to: 1. Discuss
      wound assessment and documentation relative to current practices and potential
      legal implications. 2. Describe recommendations to improve the consistency and
      accuracy of wound assessment and documentation.

PMID- 16639224
TI  - On freedom of the scientific press: can you trust the information you read in
      nursing journals?

PMID- 16639225
TI  - 'Those people': a poverty of understanding jeopardizes care of the poor.

PMID- 16639227
TI  - Preventing functional decline.

PMID- 16639228
TI  - Compassion for the mentally ill.

PMID- 16639229
TI  - Wounded soldiers.

PMID- 16639230
TI  - The fertility window.

PMID- 16639232
TI  - Leadership skills.

PMID- 16639233
TI  - Serious play.

PMID- 16639239
TI  - Understanding medical futility: two Texas cases illustrate the dilemmas for
      families, hospitals--and nurses.

PMID- 16639241
TI  - Clostridium difficile: familiar pathogen, changing epidemiology: a virulent
      strain has been appearing more often, even in patients not taking antibiotics.

PMID- 16639243
TI  - Postpartum depression: it isn't just the blues.
AB  - Postpartum depression is a crippling mood disorder, historically neglected in
      health care, leaving mothers to suffer in fear, confusion, and silence.
      Undiagnosed it can adversely affect the mother-infant relationship and lead to
      long-term emotional problems for the child. This article differentiates
      postpartum depression from other postpartum mood and anxiety disorders and
      addresses these aspects of postpartum depression: symptoms, prevalence, risk
      factors, interventions, and the effects on relationships and child development.
      Instruments available to screen for postpartum depression are also reviewed.

PMID- 16639246
TI  - Earthquake relief in Pakistan: international aid and a mild winter have helped
      avert a second disaster.

PMID- 16639248
TI  - Syringe-exchange programs and HIV prevention: if they're effective, what's the
      controversy?
AB  - Injection drug users and their sexual partners and children represent an
      increasing proportion of Americans living with HIV or AIDS. Syringe-exchange
      programs (SEPs), which are based on the theory of harm reduction, are effective
      in preventing the transmission of HIV and other pathogens through injection drug
      use. Most programs also serve as gateways to other vital medical services. Yet
      SEPs remain controversial. This article describes the controversy, considers the
      evidence, and discusses the nursing implications.

PMID- 16639257
TI  - Self-determination vs. better treatment?: nurses, nursing groups differ over
      merits of assisted-death measures.

PMID- 16639259
TI  - The ANA seeks investment in nursing workforce development: safe patient handling
      and staffing at the forefront.

PMID- 16639264
TI  - Keeping yourself safe: ask the right questions--right from the start.

PMID- 16639265
TI  - The impending end to the stigma of wearing ear devices and its revolutionary
      implications.

PMID- 16639266
TI  - Tympanometric changes in an experimental myringosclerosis model after
      myringotomy.
AB  - HYPOTHESIS: The goal of this experimental study was to investigate the specific
      effect of myringosclerosis on tympanograms in the tympanic membranes of
      myringotomized rats by using otomicroscopy, tympanometry, and histopathology.
      BACKGROUND: Myringosclerosis is a common sequela of ventilation tube treatment of
      otitis media with effusion. The condition involves the hyalinization and
      calcification of the collagen layer in certain areas of the tympanic membrane.
      Previous animal experiments suggest an intimate relationship between the
      formation of myringosclerosis and an increased oxygen concentration in the
      environment of the wound after myringotomy. The result of a myringotomy therefore
      is an increased production of free oxygen radicals, initiating irreversible
      tissue damage involving fibrosis, hyalin degeneration, and finally apoptosis as
      observed in myringosclerosis. We propose an experimental model specific for
      creating sclerotic plaques solely on the tympanic membrane and for performing
      tympanometric measurements on this pure myringosclerosis model without creating
      any abnormality in the middle ear to test in what proportion myringosclerosis
      contributes to decrease of amplitude in tympanograms. METHODS: To assess the
      normal tympanometric values of Wistar albino rats, the pressure and peak
      admittance of the left middle ears were measured using a semiquantitative
      computerized clinical admittance meter using a sound frequency of 226 Hz. Twelve
      animals were randomly selected for the myringotomy group and perforations in the
      left ears were created. All tympanic membrane perforations in this group had
      healed and closed prior to the otomicroscopic examination and no pathologic
      reaction was observed in the external ear canals of rats. Otomicroscopic and
      tympanometric measurements were carried out on Day 15 and the degree of
      myringosclerosis was noted before the animals were killed. Twelve specimens in
      the myringotomy group were histopathologically examined for the presence of
      myringosclerotic plaques. RESULTS: Under light microscopy, extensive sclerotic
      lesions were found in the tympanic membranes of the myringotomy group, and these
      sclerotic deposits were located in the lamina propria. The myringosclerosis
      occurred predominantly adjacent to the handle of the malleus, but also near the
      annular region. In all ears with myringosclerosis, the magnitude of the maximum
      admittance reduced to approximately 50% of the Day-0 values, and this reduction
      was statistically significant (Z=-3.061, p=0.002). CONCLUSION: The present
      findings in this study are consistent with the fact that the movement of the
      tympanic membrane is hampered by lesions of sclerotic material, resulting in a
      decrease of amplitude in tympanograms (such as Type As) without any effusion or
      inflammation in the middle ear.

PMID- 16639267
TI  - The phenotype of the first otosclerosis family linked to OTSC5.
AB  - OBJECTIVE: To report the audiometric and radiologic findings in the first
      otosclerosis family linked to OTSC5. STUDY DESIGN: A clinical investigation of a
      family linked to OTSC5, including analyses of audiometric data and of high
      resolution computed tomography (CT) images of the temporal bones from genetically
      affected family members. SETTING: Tertiary referral center. PATIENTS: Family
      members from a four-generation pedigree with otosclerosis segregating as an
      autosomal dominant trait. MAIN OUTCOME MEASURE(S): Pre-surgery pure tone
      audiometric data. Classification of otosclerotic foci on high-resolution spiral
      CT images of the temporal bones of genetically affected individuals. RESULTS:
      Audiometric data showed a considerable degree of phenotypic variability. Cross
      sectional regression analysis did not disclose any clear age dependence of
      threshold-related data. Systematic differences between mean parameter values
      relating to the thresholds in the best or the worst ear were found. High
      resolution CT images revealed a fenestral otosclerotic focus in seven of nine
      (78%) clinically affected individuals and cochlear foci in one of these seven
      patients. CONCLUSION: The phenotype of OTSC5 seems to be variable. Additional
      long-term audiometric data are needed to construct age-related typical
      audiograms, which may also facilitate the comparison between phenotypes of the
      different otosclerosis loci. The detection rate of otospongiotic foci in our
      study group is similar or lower compared with previous reports on CT data in
      consecutive otosclerosis patients who had stapes replacing surgery.

PMID- 16639268
TI  - Presbycusic neuritic degeneration within the osseous spiral lamina.
AB  - OBJECTIVE: To describe a neglected anatomic variant occurring with presbycusis.
      STUDY DESIGN: Retrospective temporal bone histopathology study. METHODS:
      Quantitative analysis of peripheral hair cells, neurites, neurons, and the stria
      vascularis in temporal bones from individuals who had presbycusis. Fifty-three
      patients aged 65 years or older and with a down-sloping audiogram and clinical
      diagnosis of presbycusis were reviewed. Nine cases had normal hair and ganglion
      cell populations but reduced peripheral processes (neuritic presbycusis). These
      were compared with five normal-hearing controls on measurements of anterior
      middle and basal turn fiber bundle diameter and the ratio of basal to middle
      diameters. RESULTS: Thresholds at 4 and 8 kHz were significantly poorer in the
      neuritic presbycusis group than in the control group (p<or=0.004 and 0.05,
      respectively), as was speech discrimination score (p<or=0.028). The ratio of
      basal to middle turn diameters was significantly smaller in the neuritic
      presbycusis group (p<or=0.003). This effect was quite marked in that there was no
      overlap in ratios between the groups, with the maximum neuritic presbycusis group
      ratio smaller than the minimum control group ratio. There was a moderate negative
      correlation between ratio and threshold at 4 kHz (sigma=-0.49, p<or=0.075).
      CONCLUSION: Loss of peripheral neurites in the anterior basal cochlear segment is
      found in conjunction with presbycusis in temporal bones that have no other
      morphologic abnormalities. These cases can be identified by a gradual down
      sloping audiogram in contrast to sensory (hair cell) presbycusis, which is
      characterized by a precipitous high tone loss.

PMID- 16639269
TI  - Cochleovestibular and ocular features in a Dutch DFNA11 family.
AB  - OBJECTIVES: To report hearing impairment and vestibular and ocular features in a
      Dutch DFNA11 family and to compare these results to reported data on three other
      DFNA11 families. STUDY DESIGN: Family study. METHODS: Regression analysis was
      performed in relation to age to outline the development of hearing thresholds and
      speech recognition scores. Vestibular and ocular functions were examined.
      RESULTS: First symptoms of hearing impairment started between the ages of 4 and
      43 years. Most of the audiograms were symmetric and flat or downsloping. The
      annual threshold deterioration increased from 0.2 to 2.6 dB per year at 0.25 to 8
      kHz in the longitudinal analyses and in the cross-sectional analysis from 0.3 to
      0.9 dB per year. The speech recognition score was quite good, deteriorating by
      0.9% per year from a 90% score at the age of 36 years onward. Remarkably,
      extensive ocular examination including corrected visual acuity and refraction
      measurements, slit-lamp examination, ophthalmoscopy, Goldmann perimetry,
      electroretinography and electro-oculography revealed signs of subclinical retinal
      dysfunction. None of the patients showed the classic triad of retinitis
      pigmentosa. Pure-tone thresholds, phoneme recognition scores, and vestibular
      responses of the mutation carriers were fairly similar to previously described
      DFNA11 families. CONCLUSION: Even though the diverse mutations are located in
      different regions of the myosin VIIa gene, the cochleovestibular phenotype is
      fairly similar in all DFNA11 families. Surprisingly, only in this family was
      subclinical retinal dysfunction detected.

PMID- 16639270
TI  - Cochlear implant explantation as a sequela of severe chronic otitis media: case
      report and review of the literature.
AB  - INTRODUCTION: In the 1980s, intracranial and inner ear infections were feared
      complications in patients with recurrent or chronic otitis media (COM) who had
      undergone cochlear implantation. Current studies show a low incidence of such
      complications. We present a case of a patient who developed severe COM requiring
      cochlear explantation. CASE: Our patient had a previous cleft palate repair and
      as a three-year-old was implanted with a Nucleus-24 implant. She developed
      chronic otorrhea in the implanted ear, which was managed by her pediatrician
      until her cochlear implant stopped functioning. Radiographic imaging revealed
      erosion of the cochlea and extrusion of the distal electrode medially in the
      petrous apex. SETTING: Tertiary care university hospital. INTERVENTION/RESULTS:
      The patient underwent cochlear explantation, subtotal petrosectomy, obliteration
      of ear, and intravenous antibiotic therapy. One month later she was implanted in
      the contralateral ear. CONCLUSION: COM poses potentially severe complications in
      patients receiving cochlear implants. Patients receiving cochlear implants who
      are at high risk for COM require follow-up for an extended period of time.

PMID- 16639271
TI  - Cochlear implantation with ipsilateral petroclival chondrosarcoma.
AB  - OBJECTIVE: To highlight a case of cochlear implantation in the setting of
      ipsilateral petrous apex chondrosarcoma. BACKGROUND: A patient with bilateral
      progressive hearing loss was incidentally found to have a destructive right
      petrous apex lesion on computed tomography before cochlear implantation. The
      patient had no associated symptoms and a magnetic resonance imaging scan was
      obtained, narrowing the differential diagnosis. A middle cranial fossa approach
      was performed for synchronous biopsy of the lesion and cochlear implantation.
      RESULTS: Frozen sections revealed a low-grade chondroid lesion, and a Med-El
      Combi 40+ cochlear implant with a split electrode array was inserted via the
      middle fossa. Final pathologic examination revealed a Grade I chondrosarcoma. The
      patient suffered no complications postoperatively and was followed-up over 5
      years with serial computed tomographic scans and clinical examinations. No
      additional treatment was administered. Eighteen months postoperatively, the
      patient experienced episodic vertigo. There were no new findings on computed
      tomography, and the vertigo improved with a low-salt diet. Otherwise, the patient
      had excellent hearing results, and the lesion has not progressed under
      observation. CONCLUSION: The implications of observing low-grade chondrosarcomas
      in well-selected patients and the unique aspect of cochlear implantation on the
      affected side are discussed.

PMID- 16639272
TI  - Is there loss of vibration amplitude across the snap coupling of the bone
      anchored hearing aid?
AB  - HYPOTHESIS: There is loss of vibration transmission across the snap coupling
      connecting the Bone-Anchored Hearing Aid transducer to the implanted abutment on
      the head. BACKGROUND: The only nonrigid part of the Bone-Anchored Hearing Aid
      system is the connection between the output of the transducer and the abutment.
      Vibration losses across the coupling have not been previously measured. If a loss
      is found, a change in design could improve the efficiency of the Bone-Anchored
      Hearing Aid. This would be very helpful in borderline cases in which the Bone
      Anchored Hearing Aid does not have enough power to achieve adequate hearing
      threshold levels. METHODS: A laser Doppler vibrometer was used to measure
      vibrations on the output stem and four points on the abutment of the Bone
      Anchored Hearing Aid. The Bone-Anchored Hearing Aid was coupled to a dry skull
      through a plexiglas bite bar screwed to the skull. The impedance load was varied
      by fixing the skull. A control loose coupling was measured. Five Bone-Anchored
      Hearing Aid Compacts were measured. RESULTS: There was little loss across the
      Bone-Anchored Hearing Aid snap coupling. At frequencies above 500 Hz, there was
      no more than 5-dB loss at any frequency. Changing the impedance load by fixing
      the skull did not change the loss across the coupling. CONCLUSION: The snap
      coupling is an efficient means of transmitting vibrations to the skull. There is
      little loss of vibration attenuation across it. Increases in functional Bone
      Anchored Hearing Aid amplification gain cannot be achieved by further optimizing
      this interface.

PMID- 16639273
TI  - Cranial thickness in superior canal dehiscence syndrome: implications for canal
      resurfacing surgery.
AB  - OBJECTIVE: To use morphometric analyses of cranial thickness to investigate 2
      cases of unanticipated calvarial bone resorption in superior canal dehiscence
      (SCD) resurfacing surgery. DESIGN: Retrospective morphometric analysis of high
      resolution computed tomography (CT) temporal bone scans in normal and control
      subjects with accompanying case reports. SETTING: Tertiary care referral center.
      PATIENTS: Two patients with SCD and failed resurfacing because of bone
      resorption. Temporal bone CT scans from 30 sex-matched controls. INTERVENTION:
      Resurfacing of SCD via a middle fossa approach using a split thickness calvarial
      graft from the craniotomy site. MAIN OUTCOME MEASURE: Mean cross-sectional area
      of the middle fossa craniotomy bone flap and mean cranial thickness at 30 and 45
      degrees above the middle fossa floor. RESULTS: Two patients had delayed failure
      of SCD resurfacing surgery as manifested by return of symptoms. High-resolution
      CT scans in both, and intraoperative confirmation in one, confirmed resorption of
      the bone graft. Measurements of cross-sectional area of the middle fossa
      craniotomy on high-resolution CT scans demonstrated significantly reduced values
      in the two SCD patients as compared with normal controls (Mann-Whitney U test,
      p<0.05). Cranial thickness outside the squamous temporal bone was reduced but did
      not reach statistical significance. CONCLUSION: Morphometric measurements of the
      calvarium have demonstrated that the squamous temporal bone is thinner in
      patients with SCD as compared with controls. Thus, the process leading to defects
      in the tegmen extends beyond the petrous pyramid. This suggests that there may be
      extratemporal factors leading to the development of a dehiscence. These findings
      also have implications for the surgical treatment of this disorder. Resurfacing
      methods may have a higher failure rate as the bone graft has reduced mass and
      maybe prone to resorption. Canal plugging methods may provide a more definitive
      means of addressing the dehiscent labyrinth than resurfacing.

PMID- 16639274
TI  - Meniere's disease: prevalence of contralateral ear involvement.
AB  - OBJECTIVE: Determine the prevalence and time interval for conversion from
      unilateral to bilateral involvement in Meniere's disease and cochlear hydrops.
      STUDY DESIGN AND SETTING: Retrospective chart review in a tertiary otologic
      referral center. PATIENTS: 232 patients diagnosed with Meniere's Disease (n=186)
      or cochlear hydrops (n=46) between 1959 and 2001, who visited the clinic over a
      five-year period between 1997-2001 and have at least 2 audiograms more than 12
      months apart. MAIN OUTCOME MEASURES: Prevalence of cochlear hydrops relative to
      Meniere's Disease, rate of progression from unilateral to bilateral involvement;
      interval between unilateral onset of symptoms and bilateral involvement; and rate
      of progression from cochlear hydrops to Meniere's disease. RESULTS: Initial
      diagnosis was Meniere's disease in 71% and cochlear hydrops in 29% of all 950
      hydropic patients presenting between 1997 and 2001. In the study sample,
      Meniere's disease was bilateral at presentation in 11%; an additional 12% (14% of
      unilaterals) became bilateral during the follow-up period. At presentation, 6.5%
      of cochlear hydrops patients were bilateral, with another 26% becoming bilateral.
      Conversion from cochlear hydrops to Meniere's disease occurred in 33% and some of
      these are included among the bilateral. The average time interval for conversion
      from unilateral to bilateral Meniere's was 7.6 years (SD=7.0 years). CONCLUSION:
      Most otologists are aware of the potential for contralateral ear involvement and
      conversion from cochlear hydrops to Meniere's disease after diagnosis. These
      changes are significant, require long-term follow-up for detection, and may
      necessitate further treatment. Patients should be counseled regarding this
      potential when interventions are considered, especially with respect to ablative
      treatments.

PMID- 16639275
TI  - Three-dimensional analysis of benign paroxysmal positional nystagmus in a patient
      with anterior semicircular canal variant.
AB  - OBJECTIVE: To show the positional nystagmus in a patient who had suffered from
      benign paroxysmal positional vertigo (BPPV) that was thought to be caused by
      involvement of the anterior semicircular canal (ASCC) (A-BPPV). STUDY DESIGN:
      Retrospective case report. SETTING: City hospital. PATIENT: The present study
      reports a rare case of A-BPPV in a 41-year-old woman. CASE REPORT: The patient is
      41-year-old woman who developed a positional vertigo after playing volleyball on
      March 22, 2005 and consulted our hospital the next day. When left Dix-Hallpike
      maneuver was performed, she showed a positional nystagmus of which fast phase
      direction of the torsional component was clockwise while that of the vertical
      component was downward. We plotted the slow phase eye velocity of the positional
      nystagmus during the left Dix-Hallpike maneuver on three-dimensional coordinates
      that showed the axis of the positional nystagmus to be perpendicular to the plane
      of the right ASCC. CONCLUSION: These results suggested that the patient was
      suffering from A-BPPV.

PMID- 16639276
TI  - Value of lying-down nystagmus in the lateralization of horizontal semicircular
      canal benign paroxysmal positional vertigo.
AB  - BACKGROUND: Horizontal canal benign paroxysmal positional vertigo is
      characterized by horizontal direction-changing nystagmus induced by lateral head
      turning in supine position. According to Ewald's second law, the direction of
      head turning that creates a stronger response represents the affected side in
      geotropic nystagmus and the healthy side in apogeotropic nystagmus. However, it
      may not always be possible to lateralize the involved ear only by comparing the
      intensity of the nystagmus. We studied the values of nystagmus induced by
      position change from sitting to supine in the lateralization of horizontal canal
      benign paroxysmal positional vertigo. METHODS: A retrospective study of 54
      patients who had been diagnosed as having horizontal canal benign paroxysmal
      positional vertigo at the Dizziness Clinic of Seoul National University Bundang
      Hospital from May 2003 to February 2004 was performed. The directions of the
      nystagmus induced by lying down were compared with those determined by Ewald's
      second law. RESULTS: Of the 54 patients, 32 (20 apogeotropic and 12 geotropic)
      showed horizontal nystagmus induced by lying down. The nystagmus tended to be
      ipsilesional in apogeotropic patients (80%) and contralesional in their geotropic
      counterparts (75%). CONCLUSION: In horizontal canal benign paroxysmal positional
      vertigo, lying-down nystagmus mostly beats toward the involved ear in the
      apogeotropic type and directs to the healthy ear in the geotropic type. The
      direction of lying-down nystagmus may help lateralizing the involved ear in
      horizontal canal benign paroxysmal positional vertigo.

PMID- 16639277
TI  - Transient evoked otoacoustic emissions pattern as a prognostic indicator for
      hearing preservation in acoustic neuroma surgery.
AB  - OBJECTIVE: To determine whether pre-operative transient otoacoustic emission
      (TEOAE) patterns are predictive of successful hearing preservation in acoustic
      neuroma surgery. STUDY DESIGN: Retrospective observational study. SETTING:
      Tertiary referral medical center. PATIENTS: A convenience sample was identified
      in whom pre-operative TEOAE data were available in patients undergoing acoustic
      neuroma surgery from 1993-2004. Ninety-three patients were identified who met
      this inclusion criterion. INTERVENTIONS: Subjects underwent attempted hearing
      preservation surgery via middle cranial fossa or retrosigmoid approaches. Routine
      audiometry, ABR, and TEOAE. MAIN OUTCOME MEASURES: Pre- and post-operative pure
      tone and speech results were categorized into hearing classes A, B, C, and D as
      described in the American Academy of Otolaryngology guidelines (1995). Hearing
      preservation was defined by maintenance of the pre-operative hearing class or
      downgrade to within one hearing class post-op. Pre-operative TEOAE results were
      divided into five frequency bands and described as positive in each band if there
      was a response above the noise floor with >50% reproducibility. RESULTS: Hearing
      was preserved in 51 patients (55%). Of these, 11 (22%) had positive TEOAE
      response in all five frequency bands measured (1, 1.5, 2, 3, 4 kHz), whereas 40
      (78%) had TEOAE responses ranging from 0 to 4 frequency bands. 42 patients failed
      to preserve their hearing. Of these, only three (7%) had positive TEOAE in all
      five frequency bands, and 39 (93%) had TEOAE responses ranging from 0 to 4
      frequency bands (p<0.05). Other variables of prognostic significance to hearing
      preservation in our series included smaller tumor size, tumor location within the
      IAC, better pre-operative hearing, and shorter latencies on ABR. Logistic
      regression was then used to compare the prognostic value of TEOAE against these
      variables. In our series, ABR latencies and 5 frequency band response on TEOAE
      showed the highest significant correlation to hearing preservation (p<0.05).
      CONCLUSION: A robust pre-operative TEOAE frequency band pattern may be used as a
      favorable prognostic indicator for potential hearing preservation in acoustic
      neuroma surgery. The prognostic value may be enhanced when combined with other
      prognostic factors such as tumor size, tumor location, pre-operative ABR and
      audiometric results.

PMID- 16639278
TI  - Small acoustic neuromas: surgical outcomes versus observation or radiation.
AB  - OBJECTIVE: Evaluate factors affecting outcomes of small acoustic neuroma (AN)
      removal via a middle cranial fossa (MCF) approach, and compare results to
      published data on observation and radiation therapy. STUDY DESIGN: Retrospective
      chart review. SETTING: Academic tertiary referral center. METHODS: 162
      consecutive patients (ages 19-70) with unilateral AN (0.2-2.5 cm in largest
      dimension) removed through a MCF approach were reviewed focusing on preservation
      of hearing, facial nerve function and complications. One hundred thirteen
      patients had pre-operative word recognition scores (WRS)>70%. RESULTS: Both tumor
      size and pre-operative WRS were related to post-operative WRS (p<0.01). Overall,
      at least some hearing was preserved in 94 (60%) of the 156 patients who had
      hearing before surgery. If the WRS was also >70% (N=113), 56 (50%) maintained
      WRS>70%. Importantly, WRS for 12 others improved to >70% after surgery. When the
      patients were stratified by tumor size, the patients with small tumors (2-10 mm)
      faired better than the overall group. At least some hearing was preserved in 65
      (72%) of the 90 patients. If the WRS was also >70% (N=66), 39 (59%) maintained
      WRS>70%. WRS for eight others improved to >70% after surgery. When the tumor was
      1.1-1.4 cm (N=34), the chance of preserving some hearing decreased to 42%
      (14/33). If the WRS was also >70% (N=23), 9 (39%) maintained WRS>70%. WRS for
      three others improved to >70% after surgery. When the tumor reached 1.5-2.5 cm
      (N=35), the hearing preservation rate was 43%. If the WRS was also >70% (N=24),
      only eight (33%) maintained WRS of 70%, and one other improved to >70%. The
      addition of intra-operative whole eighth nerve near field monitoring improved
      results during small tumor (<or=1.0 cm) removal preserving some hearing in 80%
      (32/40) and preserving >70% WRS in 76% (22/29) of those with >70% pre-operative
      WRS. Good facial nerve function (HB I-II) was achieved in 97% (86% HB I). When
      tumor size was <or=1.0 cm (N=93), however, good facial nerve function was
      obtained in 100% (94% HB I). Complications included CSF leak: 9 (5.5%); seizure:
      2 (1.2%); and recurrence: 1 (0.6%). CONCLUSION: Our results suggest that removal
      of unilateral AN through an MCF approach when the tumor is small and hearing is
      good provides the best opportunity for hearing preservation and normal facial
      nerve function. Observation historically results in tumor growth in young and
      middle-age patients with subsequent hearing loss. Radiation may prevent most
      tumors from growing, and more data are needed to determine long-term tumor
      control and hearing preservation rates.

PMID- 16639279
TI  - Magnetic resonance appearance of the inner ear after hearing-preservation
      surgery.
AB  - OBJECTIVE: To determine whether the appearance of the inner ear on T2-weighted
      follow-up magnetic resonance imaging correlates with hearing status after hearing
      preservation surgery for vestibular schwannoma. STUDY DESIGN: Retrospective chart
      review. SETTING: Tertiary referral medical center. PATIENTS: The study includes
      patients undergoing hearing-preservation surgery for vestibular schwannoma from
      1998 to 2003. INTERVENTION: Diagnostic evaluation with magnetic resonance imaging
      and audiometric evaluation. MAIN OUTCOME MEASURES: Hearing results as reported in
      charts was correlated with appearance of membranous labyrinth on T2-weighted
      magnetic resonance images obtained at least 1 year after surgery. RESULTS: Twenty
      nine patients were identified, 16 of whom satisfied the inclusion criteria. All
      16 of the patients underwent middle fossa removal of vestibular schwannoma.
      Serviceable hearing according to American Academy of Otolaryngology-Head and Neck
      Surgery criteria was preserved in eight patients (50%). Of the eight patients
      without serviceable hearing, six had the cochlear nerve sacrificed at the time of
      surgery. All patients with serviceable hearing had normal appearing
      cochleovestibular signal on T2-weighted images, whereas six of eight patients
      (75%) with no hearing or poor hearing had abnormal low signal in the inner ear,
      suggesting inner ear ossification. The positive predictive value of a normal
      labyrinth for preserved hearing was 90%, whereas the negative predictive value of
      an abnormal labyrinth for no hearing was 100%. All but one patient who had the
      cochlear nerve sacrificed showed abnormal morphology of the labyrinth on T2
      weighted magnetic resonance imaging. CONCLUSION: We describe the T2-weighted
      magnetic resonance findings after hearing-preservation surgery for acoustic tumor
      removal. Loss of inner ear signal on T2-weighted images correlates with loss of
      hearing postoperatively, whereas preserved inner ear signal correlates with
      hearing preservation after middle fossa surgery for vestibular schwannoma
      removal.

PMID- 16639280
TI  - Resection of a recurrent paraganglioma via an endoscopic transnasal approach to
      the jugular fossa.
AB  - OBJECTIVE: To present a novel endoscopic, transnasal approach to a recurrent
      paraganglioma of the jugular fossa (glomus jugulare). STUDY DESIGN: Case report
      and review of the literature. SETTING: The study was carried out at the
      University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A.
      PATIENT: A 64-year-old woman presented to the University of Pittsburgh Medical
      Center with a 9-month history of left otalgia, occasional vertigo, facial pain,
      and recurrent epistaxis. She had undergone two previous procedures over the past
      35 years for a glomus tympanicum. Physical examination revealed a mass in the
      left nasopharynx originating from the eustachian tube. A computed tomographic
      scan revealed an expansive mass in the left jugular foramen extending into the
      posterior parapharyngeal space suggestive of a large jugular paraganglioma.
      INTERVENTION: The patient underwent preoperative embolization of the
      paraganglioma. An endoscopic, transnasal approach along the eustachian tube, the
      ascending parapharyngeal carotid artery, and into the jugular fossa was used to
      remove the tumor. Intraoperative image guidance assisted in the identification of
      key anatomic landmarks. RESULTS: Postoperative magnetic resonance imaging
      revealed a thin rim of enhancement at the posterior aspect of the jugular fossa
      consistent with residual tumor. The patient was discharged to home on
      postoperative Day 1 in stable condition. There have been no complications with 4
      months of follow-up, and the left facial paralysis secondary to preoperative
      embolization has resolved. CONCLUSION: We report the successful subtotal
      resection of a recurrent paraganglioma via a novel endoscopic, transnasal,
      transclival, transpetrous approach with image guidance. This approach allowed the
      near-total resection of a recurrent glomus jugulare with minimal surgical
      morbidity. Technological advances and surgical experience with nasal endoscopy
      and image guidance allow minimally invasive surgical management of select
      extracranial lesions of the lateral cranial base.

PMID- 16639281
TI  - Quality of life after acoustic neuroma surgery.
AB  - OBJECTIVE: The aim of this study is to assess patients' quality of life after
      acoustic neuroma surgery, and if some patients' characteristics, parameters of
      tumor and surgical parameters affect patients' quality of life. STUDY DESIGN:
      Retrospective study. SETTING: Tertiary care center. PATIENTS: A group of 386
      patients who underwent acoustic neuroma surgery. INTERVENTION: Patients included
      were derived from a population of 459 subjects operated for acoustic neuroma by
      the Otologic Group of Piacenza. MEAN OUTCOME MEASURE: The outcome of the
      questionnaires on quality of life (SF 36), the Dizziness Handicap Inventory (DHI)
      and a questionnaire of patients' histories were analyzed. RESULTS: In our sample
      a group of 231 patients were asymptomatic after surgery, while 155 patients
      reported very really disabling symptoms. Hearing loss was perceived as the most
      disabling symptom. The scores of questionnaire on quality of life were lower than
      scores for the normal population. The indices of disablement influenced the
      perception of quality of life. CONCLUSION: Our study has shown that patients
      perceived a worsening of their quality of life, in particular women and patients
      over 45. Surgery caused a higher percentage of disability. Patients' quality of
      life can be used as a parameter for the timing of surgery. Our data indicate that
      an early surgical approach for intrameatal tumor is better than waiting for an
      increase in the tumor size. A "wait-and-scan" strategy for extrameatal neuromas
      which do not affect the brainstem is preferable, since these patients have a
      worsening of their quality of life after surgery independently of the tumor size.

PMID- 16639282
TI  - Radiology of the petromastoid canal.
AB  - OBJECTIVE: The petromastoid canal is a thin structure that connects the mastoid
      antrum with the posterior cranial fossa and houses subarcuate blood vessels and
      prolongation of the dura. The current retrospective study was designed to
      investigate radiology of the petromastoid canal in different age groups and to
      determine whether increasing the scanner's resolution could enhance the detection
      capability of this structure. METHODS: Axial sections of 504 high-resolution
      computed tomographic images obtained with 0.6-, 1.1-, or 1.3-mm-thick slices
      through the petrous bones were reviewed. Sixteen asymmetric images were excluded
      from the statistical analysis. Type I petromastoid canal was invisible; Type II
      and Type III appeared as thin channels less than 0.5 and 0.5 to 1 mm in width,
      respectively, and Type IV was greater than 1 mm wide. RESULTS: The petromastoid
      canal Type II was detected more frequently in patients older than 5 years
      (p<0.0001) and Type IV was demonstrated more often in children up to age 5 years
      (p<0.0001). The occurrence of a Type I petromastoid canal was not dependent on
      the age of the patients or the resolution of the images (p=0.82). Increasing the
      resolution failed to improve the visibility of the petromastoid canal or the
      ability to detect it. A wide petromastoid canal (>2 mm) was significantly more
      common in younger patients (22.2% versus 2.4% in the older group) (p<0.0001). A
      petromastoid canal beginning medially directly from the internal auditory canal
      was detected in 4 of 488 (0.8%) images. The lateral opening of the petromastoid
      canal can be found posteriorly to the medial orifice, anteriorly to it, or at the
      same level. The posterior lateral opening was demonstrated to be more common than
      the other two types in patients younger than 5 years, and the anterior opening
      was detected more frequently in older patients (p=0.0006). CONCLUSION: The shape
      and width of the petromastoid canal differ radiologically between populations
      younger and older than 5 years of age. The findings of the current study may be
      important for otolaryngologists engaged in cochlear implantation or involved in
      treating otogenic intracranial complications, especially in young children.

PMID- 16639283
TI  - Stem cell therapy for hearing loss: Math1 overexpression in VOT-E36 cells.
AB  - HYPOTHESIS: VOT-E36 cells acquire mechanosensitivity after mammalian atonal
      homolog 1 (Math1) overexpression. BACKGROUND: VOT-E36 cells are derived from a
      population of epithelial cells in the ventral region of the otocyst at embryonic
      Day 10.5, before hair cell differentiation. These cells express a number of
      specific molecular markers for hair cells under both proliferation and
      differentiation states. Overexpression of Math1 can convert nonsensory epithelial
      cells into hair cells in the cochlea. Based on this information, we tested
      whether VOT-E36 cells can be converted into hair cells by Math1 overexpression.
      METHODS: Using reverse transcriptase-polymerase chain reaction-based analysis, we
      first compared the expression patterns of various molecular markers for hair cell
      development in VOT-E36 cells between proliferation and differentiation states,
      and also before and after overexpression of Math1. Subsequently, with a standard
      calcium imaging method, we examined whether VOT-E36 cells overexpressing Math1
      could detect mechanical vibrations and activate spiral ganglion neurons in a
      coculture model. In addition, using confocal and scanning electron microscopes,
      we examined morphologic changes of VOT-E36 cells after Math1 overexpression.
      RESULTS: Consistent with previous reports, this study has shown that VOT-E36
      cells express a number of specific molecular markers for hair cells in both
      proliferation and differentiation states. Under appropriate culture conditions,
      Math1 is transiently expressed in this cell line during conditional
      differentiation. In VOT-E36 cells overexpressing Math1, the normal expression
      pattern of certain molecular markers for mature hair cells is partially restored.
      Interestingly, after coculture with spiral ganglion neurons, VOT-E36 cells
      overexpressing Math1 are able to respond to mechanical vibrations and activate
      spiral ganglion neurons. Possible molecular mechanisms underlying this novel
      finding have been explored. CONCLUSION: Math1 overexpression can partially
      restore presumably downstream signaling cascades for normal hair cell
      differentiation in VOT-E36 cells, which are able to detect mechanical vibrations
      after being cocultured with spiral ganglion neurons.

PMID- 16639284
TI  - Terminal differentiation and mitogen-activated protein kinase signaling in human
      cholesteatoma epithelium.
AB  - OBJECTIVES: To investigate whether--in cholesteatoma epithelium--terminal
      differentiation, resulting in high involucrin expression, is associated with
      mitogen-activated protein kinase (MAPK) signaling. BACKGROUND: Alterations in
      specific signal transduction pathways may explain abnormal differentiation of the
      keratinocytes in cholesteatoma. Signaling pathways used by eukaryotic cells to
      transduce extracellular signals into cellular responses converge on activated
      mitogen-activated protein kinases, mainly extracellular signal-regulated kinase,
      c-Jun NH2-terminal kinase, and p38. METHODS: Tissue samples were taken from 16
      patients with acquired cholesteatoma. Histologic examination showed that 12 of
      the 16 cholesteatomas were inflamed. Immunohistochemical methods were used to
      determine expressions of involucrin and the activated form of p38, extracellular
      signal-regulated kinase, and c-Jun NH2-terminal kinase proteins. The results
      obtained from cholesteatoma tissue were compared with paired control samples from
      retroauricular skin. RESULTS: We demonstrated increased levels of involucrin and
      increased levels of the activated forms of p38 and ERK1/2 in cholesteatoma
      epithelium when compared with control samples. No abnormality was found in the
      activation and expression of JNK1/2. A positive correlation was found between
      p38, pERK1/2, and involucrin expression (p<0.05). CONCLUSION: Our results
      demonstrate that signaling via the mitogen-activated protein kinases ERK1/2 and
      p38 is increased in cholesteatoma epithelium when compared with control skin. The
      correlations between involucrin-and phosphorylated pERK1/2 expression and between
      involucrin-and phosphorylated p38 expression indicates that terminal
      differentiation in cholesteatoma epithelium proceeds via activation of these
      mitogen-activated protein kinase signaling pathways. We discussed whether this
      increased mitogen-activated protein kinase-driven terminal differentiation is
      probably part of a keratinocyte survival program or caused by an inflammation
      induced cellular stress response.

PMID- 16639285
TI  - Identification of 2.3-Mb gene locus for congenital aural atresia in 18q22.3
      deletion: a case report analyzed by comparative genomic hybridization.
AB  - OBJECTIVE: 18q deletion syndrome is a multiple-anomaly mental retardation
      syndrome associated with congenital aural atresia. The purpose of this study was
      to determine the frequency of the congenital aural atresia phenotype in 18q
      deletion syndrome patients and to delineate a potential critical region for
      congenital aural atresia at the 18q22.3-18q23 region. STUDY DESIGN AND PATIENTS:
      The study describes one 18q deletion syndrome clinical report (Patient 15) with
      an overview of 19 other selected 18q deletion syndrome patients presenting
      congenital aural atresia from 18 published articles and one presented poster on
      18q deletion syndrome. RESULTS: Our investigation, together with the results of
      published 18q deletion syndrome reports, shows that the average frequency of
      congenital aural atresia is approximately 52%. A combination of three 18q
      deletion syndrome probands defines a chromosomal deletion site for congenital
      aural atresia at 18q22.3-18q23 in the region between markers D18S489 and D18S554.
      These polymorphic markers outline a putative critical interval of approximately
      2.3 Mb, including the genes ZNF407, ZADH2, SDCCAG33, ZNF516, FLJ44881, ZNF236,
      MBP-Golli, and GALR1. The haploinsufficiency of these genes is suggested to be a
      primary cause of congenital aural atresia phenotype in 18q deletion syndrome
      individuals. CONCLUSION: Congenital aural atresia is a relevant diagnostic clue
      and a major recognizable feature of 18q deletion syndrome. Early diagnosis of 18q
      deletion syndrome may enable application of hearing aids. Knockout studies on the
      congenital aural atresia mouse gene homolog may add further insight into the
      genes responsible for this condition.

PMID- 16639286
TI  - Histologic changes in the eustachian tube mucosa of rats after short-term
      exposure to cigarette smoke.
AB  - OBJECTIVE AND BACKGROUND: It is generally accepted that cigarette smoke is a
      major risk factor for middle ear disease. However, the literature is void of
      articles addressing the direct relationship between cigarette smoke exposure and
      middle ear disease. Furthermore, there are many conflicting opinions concerning
      the role of cigarette smoke in the pathogenesis of middle ear disease. The
      purpose of this study was to evaluate the effects of cigarette smoke on the
      Eustachian tube mucosa. MATERIALS AND METHODS: Thirty healthy 150 to 230 g
      Sprague Dawley rats with normal middle ears were used. The animals were divided
      into six groups of five. Five experimental groups (N=5 each) were exposed to a
      domestic cigarette (This, tar 7.0 mg, nicotine 0.75 mg) every 30 minutes (total
      2.5 hours, 5 cigarettes total) on a daily basis in a smoking chamber for 1, 2, 4,
      6, or 8 weeks. A control group (N=5) was placed in the same chamber without
      exposure to cigarette smoke. After exposure, the animals were sacrificed and
      cross sections of the Eustachian tubes were prepared. Histologic changes of the
      Eustachian tube mucosa were observed through light and electron microscopes.
      RESULTS: Loss of cilia, goblet cell depletion, and squamous metaplasia of the
      Eustachian tube mucosa were observed following exposure to smoke. The one- and
      two-week exposure groups demonstrated the greatest decrease in goblet cell
      counts. The eight-week exposure group showed recovery from this decrease.
      Squamous metaplasia was observed in all experimental groups and was most
      prominent in the eight-week exposure group. CONCLUSION: These findings suggest
      that cigarette smoke directly affects Eustachian tube mucosa in the early stages
      of exposure. Some of the mucosal changes, however, were reversed during the
      latter stages of exposure. A mechanism different from that which occurs in the
      nasal cavity and trachea may be activated in the Eustachian tube after exposure
      to passive smoke. The protective function of the Eustachian tube may play some
      role in this mechanism.

PMID- 16639287
TI  - Congenital bilateral oval and round window aplasia with a hypoplastic stapes.

PMID- 16639288
TI  - Familial unilateral cochlear nerve aplasia.

PMID- 16639289
TI  - Rapid hearing loss in chronic lymphocytic leukemia.

PMID- 16639290
TI  - Anatomic dissection and classic three-dimensional documentation: a unit of
      education for neurosurgical anatomy revisited.
AB  - OBJECTIVE AND IMPORTANCE: Despite development of computer-assisted neurosurgical
      navigation, learning by dissecting anatomic specimens is still important.
      CLINICAL PRESENTATION: We describe the processes from preparation of specimens
      for cranial dissection to documentation of three-dimensional (3-D) stereoscopic
      pictures, particularly focusing on the latter, which has been initiated in the
      Microneuroanatomy Laboratory, Department of Neurological Surgery, University of
      Florida. INTERVENTION: Preparation consists of irrigation of the major vessels
      and injection of colored silicone. The 3-D documentation, obtaining two pictures
      corresponding to each eye's view, is obtained by the shoot-shift-shoot method
      using a single camera mounted on a slide bar. The key of this method is correct
      shifting of the camera without alignment error to get exact 3-D effects.
      Observation of 3-D image can be made with free viewing, a 3-D viewer, or
      projection. Tips concerning all of the processes involved are described.
      CONCLUSION: The presented method of dissection and obtaining 3-D images is
      beneficial for accomplishing studies of anatomy and for providing teaching
      method.

PMID- 16639292
TI  - Visualizing the dynamics of cerebral aneurysms with four-dimensional computed
      tomographic angiography.

PMID- 16639294
TI  - Rapid administration of antifibrinolytics and strict blood pressure control for
      intracerebral hemorrhage.

PMID- 16639296
TI  - Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic
      saline.

PMID- 16639303
TI  - Chronic traumatic encephalopathy in a National Football League player.

PMID- 16639304
TI  - Microvascular retractor: a new concept of retracting and repositioning cerebral
      blood vessels.

PMID- 16639305
TI  - Delayed posttraumatic acute subdural hematoma in elderly patients on
      anticoagulation.
AB  - OBJECTIVE: To discuss delayed acute subdural hematoma (DASH), a relatively
      neglected entity, and to emphasize the potentially elevated risk for DASH among
      elderly, anticoagulated mild traumatic brain injury (TBI) patients. METHODS: The
      authors reviewed clinical and radiological data for four patients who had normal
      neurological examinations and normal computed tomographic scans after mild TBI,
      and who subsequently developed DASH and deteriorated rapidly. RESULTS: The
      patients included two men and two women, aged 65 to 86 years, who presented to
      the emergency department after mild TBI between January 2002 and June 2004. All
      were treated with chronic anticoagulation or anti-aggregation therapy. They
      deteriorated owing to DASH from 9 hours to 3 days after TBI. Three of the four
      patients underwent craniotomy for evacuation of their hematomas. One patient, who
      suffered only focal neurological deficit, was treated conservatively, and her
      hematoma gradually resolved. Two patients died and two reached Glasgow Outcome
      Scores of 3 and 4 after extended inpatient rehabilitation. CONCLUSION: A
      suspicion of DASH should be raised in elderly, anticoagulated, mild TBI patients,
      including those who present to the emergency department with Glasgow Coma Scores
      of 15 and normal computed tomographic scans after injury. Based on our
      experience, we recommend that elderly, anticoagulated mild TBI patients should be
      admitted for 24 to 48 hours of observation after injury.

PMID- 16639306
TI  - Pontine atypical neurocytoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Neurocytomas are typically located within the
      supratentorial ventricular system. Extraventricular neurocytomas are very rare,
      and this is only the second reported case of a pontine neurocytoma. We discuss
      the clinical presentation, histology, and treatment of these rare tumors.
      CLINICAL PRESENTATION: A 58-year-old man presented with a 4-month history of
      headache and unilateral facial and distal extremity paresthesia. Magnetic
      resonance imaging (MRI) scans demonstrated a 2.6 x 2.2-cm ring-enhancing cystic
      mass in the right pons. INTERVENTION: MRI-guided stereotactic biopsy yielded a
      diagnosis of atypical neurocytoma. Because of the location and malignant
      histological features of the tumor, the patient was initially treated with
      external beam radiation therapy. Several months later, MRI scans demonstrated
      tumor progression. The patient then underwent three rounds of temozolomide
      chemotherapy, during and after which his symptoms worsened. Aggressive subtotal
      resection of the tumor was achieved via a right suboccipital craniectomy.
      CONCLUSION: Twenty-eight months postoperatively, the patient is symptom free, and
      MRI scans demonstrate no evidence of residual or recurrent tumor.

PMID- 16639307
TI  - Peripheral primitive neuroectodermal tumor of the cavernous sinus: case report.
AB  - OBJECTIVE: Ewing sarcoma/peripheral primitive neuroectodermal tumors (pPNET
      family) are small, round, blue cell tumors that have a decided predilection for
      young patients and commonly arise in bone and soft tissue. We are reporting a
      rare case of cavernous sinus pPNET in a 48-year-old woman. CLINICAL PRESENTATION:
      A 48-year-old woman presented with headache, ipsilateral maxillary, and
      ophthalmic and oculomotor nerve palsies. Neuroimaging revealed a cavernous sinus
      lesion. INTERVENTION: The patient underwent debulking of the tumor, and the
      diagnosis of a pPNET was made based on histological, immunohistochemical, and
      molecular genetics (EWS-FLI1 fusion gene) findings. Bone scans, bone marrow
      aspiration, and biopsy and chest computed tomographic scans showed no evidence of
      systemic involvement. The patient had adjuvant treatment with radiotherapy and
      chemotherapy. After 14 months, the patient had no neurological deficits, and
      neuroimaging showed stable disease, although some chemotherapy complications
      occurred. CONCLUSION: This is a case of cavernous sinus pPNET in a 48-year-old
      woman, in whom the diagnosis is supported by the presence of EWS-FLI1 fusion
      gene. This seems to be the first reported case of a cavernous sinus pPNET
      confirmed by molecular genetic analysis.

PMID- 16639308
TI  - Endodermal cyst of the oculomotor nerve: case report.
AB  - OBJECTIVE: Endodermal cysts are commonly found in the anterior spinal cord.
      Reports of intracranial cases are uncommon. We report a case of endodermal cyst
      located on the left oculomotor nerve. CLINICAL PRESENTATION: A 16-year-old female
      experienced diplopia followed by headache. Neurological examinations revealed
      left oculomotor nerve palsy. Magnetic resonance imaging scans showed a well
      defined multilocular cystic mass in the proximity of the left oculomotor nerve at
      its exit from the midbrain. INTERVENTION: This patient underwent biopsy and
      drainage of the cyst. At surgery, the cyst seemed to be intrinsic to the
      oculomotor nerve and could not be totally resected. Pathological examination
      confirmed the diagnosis of endodermal cyst. CONCLUSION: Intracranial endodermal
      cysts are rare, particularly when associated with the cranial nerves. To our
      knowledge, this is the second case of endodermal cyst located on the oculomotor
      nerve. A detailed discussion and review of these case reports are presented.

PMID- 16639309
TI  - Lumbar intramedullary spinal schistosomiasis presenting as progressive
      paraparesis: case report.
AB  - OBJECTIVE AND IMPORTANCE: Blood fluke infection or schistosomiasis affects up to
      300 million people worldwide. Although infection of the hepatic and urogenital
      systems commonly occurs, central nervous system involvement is rare. When
      presenting in the spinal cord, schistosomiasis can be difficult to diagnose
      because it can present as mass lesion or transverse myelitis. We describe a
      patient with lumbar intramedullary spinal schistosomiasis who presented to a
      tertiary medical center in the United States and discuss the diagnosis and
      treatment of this rare disease. CLINICAL PRESENTATION: A 25-year-old Brazilian
      man presented with progressive, subacute, bilateral lower extremity motor and
      sensory deficits and disturbances in bladder function. Magnetic resonance imaging
      revealed a diffusely enhancing mass expanding the region of the conus medullaris.
      INTERVENTION: Laboratory investigation disclosed serum and cerebrospinal fluid
      eosinophilia. Ultimately, cerebrospinal fluid serology demonstrated the presence
      of Schistosoma mansoni. The patient was treated with praziquantel and steroids
      and made a marked recovery. CONCLUSION: The clinical and radiographic
      manifestations of spinal schistosomiasis can mimic those of intra-axial spinal
      tumors and transverse myelitis. To avoid unnecessary surgery or delay in
      treatment, the clinician must have knowledge of this type of presentation. The
      increasing volume of international travel and high prevalence of the disease
      worldwide increases the possibility that the practicing neurosurgeon in the
      United States may encounter this rare but treatable disease.

PMID- 16639310
TI  - Superficial femoral vein invasion by a benign neurofibroma in a non
      neurofibromatosis patient: case report.
AB  - OBJECTIVE AND IMPORTANCE: Neurofibromas are benign neural sheath tumors arising
      from intraneural supporting cells. Such tumors are characteristic of
      neurofibromatosis Type I (von Recklinghausen disease) but also occur
      sporadically. Vascular involvement by neurofibromata is rare, but has been
      described in the past in the context of neurofibromatosis. There is, to our
      knowledge, no description of vascular involvement by a neurofibroma in a non
      neurofibromatosis patient. CLINICAL PRESENTATION: A 40-year-old woman presented
      with a 4 year history of a right thigh mass associated with diffuse lower
      extremity pain. She had no other clinical manifestations of neurofibromatosis and
      no known family member with neurofibromatosis Type I. Magnetic resonance imaging
      scans revealed a well-defined solid mass in the anteromedial aspect of the right
      thigh closely associated with the superficial femoral vein. INTERVENTION: The
      vessel segment and encapsulated mass were resected "en bloc" after proximal and
      distal ligation of the vein. The pathological appearance of the mass was
      consistent with a benign neurofibroma that had infiltrated all layers of the
      vessel. CONCLUSION: Vessel invasion by a benign sporadic neurofibroma is a rare
      occurrence with potentially severe implications for the patient. It suggests that
      surgical removal of asymptomatic benign-appearing lesions of that type should be
      considered if they are adjacent to important anatomical structures.

PMID- 16639311
TI  - Removal of an orbital metallic foreign body to facilitate magnetic resonance
      imaging: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Magnetic resonance imaging (MRI) is the imaging
      modality of choice for brain tumors and other lesions of the central nervous
      system. However, this procedure is contraindicated in patients with orbital
      metallic foreign bodies. In such cases, the usual clinical strategy is to manage
      the patient without the benefit of MRI scans and, instead, to rely on less
      sensitive imaging modalities in particular computed tomographic scanning.
      CLINICAL PRESENTATION: Two patients, one with a posterior fossa mass and one with
      suspected central nervous system lymphoma, were seen at our institution. MRI
      scanning was recommended, but had been precluded in both patients by the presence
      of metal fragments in the orbit. INTERVENTION: In each case, the orbital foreign
      body was successfully localized and removed. Postprocedure computed tomographic
      scanning confirmed complete removal. MRI scanning was then performed without
      difficulty. The first patient underwent posterior fossa craniotomy and removal of
      the tumor, which proved to be a medulloblastoma. The second patient was found to
      have evidence of lymphoma in the cranial base and meninges and was treated with
      radiotherapy and systemic and intrathecal chemotherapy. MRI scanning provided
      superior diagnostic information and spared both patients the risks and discomfort
      of myelography and exposure to ionizing radiation from multiple computerized
      tomographic scans. CONCLUSION: Two patients with central nervous system tumors
      underwent removal of a metal fragment in the orbit for the specific purpose of
      facilitating MRI scans. This is a practical, straightforward concept, which
      should be considered when MRI scanning is needed for optimal patient management.

PMID- 16639314
TI  - Toward the emergence of nanoneurosurgery: part II--nanomedicine: diagnostics and
      imaging at the nanoscale level.
AB  - THE NOTION OF nanotechnology has evolved since its inception as a fantastic
      conceptual idea to its current position as a mainstream research initiative with
      broad applications among all divisions of science. In the first part of this
      series, we reviewed the structures and principles that comprise the main body of
      knowledge of nanoscience and nanotechnology (58). This article reviews and
      discusses the applications of nanotechnology to biological systems that will
      undoubtedly transform the foundations of disease diagnosis, treatment, and
      prevention in the future. Specific attention is given to developments in
      diagnostics and imaging at the nanoscale level. The use of nanoparticles and
      nanomaterials as biodetection agents for deoxyribonucleic acid and proteins is
      presented. In addition, nanodevices, such as nanowires, nanotubes, and
      nanocantilevers, can be combined with nanoarrays and nanofluidics to create
      integrated and automated nanodetection platforms. Molecular imaging modalities
      based on quantum dots and magnetic nanoparticles are also discussed. This
      technology has been extended to the imaging of intracranial neoplasms. Further
      innovation within these disciplines will form the basis for the development of
      mature nanomedicine. The final article of the series will focus on additional
      advancements in nanomedicine, namely nanotherapy and nanosurgery, and will cover
      the innovations that will lead to the eventual realization of nanoneurosurgery.

PMID- 16639315
TI  - What do patients with cerebral aneurysms know about their condition?
AB  - OBJECTIVE: During diagnosis and treatment, patients with cerebral aneurysms
      receive complex medical information. To study what patients know about their
      condition, we compared patients' knowledge about their aneurysm-related medical
      history with information in the medical record. METHODS: Neurosurgery clinic
      outpatients with cerebral aneurysms were interviewed about their history of
      subarachnoid hemorrhage, number of aneurysms, aneurysm treatments, and treatment
      outcomes. Corresponding data were abstracted from the medical record by study
      personnel. We used kappa scores to assess the agreement between patient responses
      and the medical record. RESULTS: The 178 study patients were predominantly women
      (71%), with a mean age of 54.4 years. The medical record showed that 56% of
      patients currently harbored an unsecured aneurysm, 53% had experienced a
      subarachnoid hemorrhage, 29% had multiple aneurysms, and 68% had undergone
      previous surgical or endovascular aneurysm treatment. Patient responses showed
      that, of the 100 patients with unsecured aneurysms, 33% were not aware that they
      harbored an unsecured aneurysm. Ninety percent of all patients knew whether they
      had experienced a subarachnoid hemorrhage (kappa = 0.81, near perfect agreement),
      78% knew how many aneurysms they harbored (kappa = 0.57, moderate agreement), and
      92% understood whether they had undergone previous aneurysm treatment (kappa =
      0.82, near perfect agreement). CONCLUSION: Most patients with cerebral aneurysms
      had an accurate understanding of many aspects of their aneurysm-related medical
      history. Of concern, patients were most often incorrect about the presence of an
      unsecured aneurysm, the issue most relevant to treatment decision-making and to
      their future risk of subarachnoid hemorrhage, stroke, and premature death.

PMID- 16639316
TI  - Cerebral ischemia as a presenting feature of intracranial aneurysms: a negative
      prognostic indicator in the management of aneurysms.
AB  - OBJECTIVE: Cerebral ischemia (stroke) can be a presenting clinical feature of
      intracranial aneurysms and may herald poor prognosis. METHODS: A retrospective
      review of admissions for aneurysms over a 6-year period revealed that 12 patients
      (5%) had stroke or stroke-like presentations among 236 patients with intracranial
      aneurysms. Patient demographics, characteristics of aneurysms, and management
      were analyzed. RESULTS: Of 12 patients reviewed, nine had anterior circulation
      aneurysms. Two patients presented with subarachnoid hemorrhage and 10 with
      unruptured aneurysms. Eleven patients had stroke at the time of presentation, and
      five had a previous history of transient ischemic attacks. Ten patients had
      hypertension and eight were active smokers. The mean size of 10 aneurysms was
      11.8 mm. Surgical extirpation of the aneurysms was performed in all cases. Four
      cases revealed thrombus in the aneurysm and one was atherosclerotic. The 6-month
      outcome was good in seven patients (58%) and fair in four patients (33%). One
      patient died. This outcome was significantly worse (P < 0.01) compared to that of
      good grade aneurysms in our database. Hypertension was a significant indicator of
      poor outcome (P < 0.02). CONCLUSION: Ischemic episodes as a presenting feature of
      intracranial aneurysms could be indicators of poor prognosis. Routine evaluation
      of stroke patients for aneurysms may help in early diagnosis. In addition,
      surgical obliteration of aneurysms could prevent subsequent strokes and
      neurological deficits.

PMID- 16639317
TI  - Apolipoprotein E epsilon 2 is associated with new hemorrhage risk in brain
      arteriovenous malformations.
AB  - OBJECTIVE: Patients with brain arteriovenous malformation (AVM) are at life
      threatening risk of intracranial hemorrhage (ICH). Identification of genetic
      variants associated with increased new ICH risk would facilitate risk
      stratification and guide therapeutic intervention. METHODS: Brain AVM patients
      evaluated at University of California, San Francisco or Kaiser Permanente
      Northern California were followed longitudinally. Primary outcome was new ICH
      after diagnosis; censoring events were any AVM treatment or last follow-up
      examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH
      was evaluated by Kaplan-Meier survival analysis and further characterized via a
      Cox proportional hazards model. RESULTS: We genotyped 284 brain AVM patients (50%
      women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a
      history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was
      associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold
      increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46
      17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and
      clinical presentation). Subset analysis in the largest homogenous ethnic
      subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2
      carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020;
      multivariate model adjusting for clinical presentation). CONCLUSION: ApoE
      genotype may influence the risk of ICH in the natural course of brain AVM. The
      identification of genetic predictors of ICH risk may facilitate estimation of AVM
      natural history risk and individualize clinical decision-making and therapeutic
      recommendations.

PMID- 16639318
TI  - Predictors of neurocognitive decline after carotid endarterectomy.
AB  - OBJECTIVE: Although the incidence of stroke after carotid endarterectomy (CEA) is
      low (1-3%), approximately 25% of patients experience subtle declines in
      postoperative neuropsychometric function. No studies have investigated the risk
      factors for this neurocognitive change. We sought to identify predictors of
      postoperative neurocognitive dysfunction. METHODS: We enrolled 186 CEA patients,
      with both symptomatic and asymptomatic stenosis, to undergo a battery of
      neuropsychometric tests preoperatively and on postoperative Days 1 and 30.
      Neurocognitive dysfunction was defined as a two standard deviation decline in
      performance compared with a similarly aged control group of lumbar laminectomy
      patients. Univariate logistic regression was performed for age, sex, obesity,
      smoking, symptomatology, diabetes mellitus, hypertension, hypercholesterolemia,
      use of statin medication, previous myocardial infarction, previous CEA, operative
      side, duration of surgery, duration of carotid cross-clamp, and weight-adjusted
      doses of midazolam and fentanyl. Variables achieving univariate P < 0.10 were
      included in a multivariate analysis. Data is presented as (odds ratio, 95%
      confidence interval, P-value). RESULTS: Eighteen and 9% of CEA patients were
      injured on postoperative Days 1 and 30, respectively. Advanced age predicted
      neurocognitive dysfunction on Days 1 and 30 (1.93 per decade, 1.15-3.25, 0.01;
      and 2.57 per decade, 1.01-6.51, 0.049, respectively). Additionally, diabetes
      independently predicted injury on Day 30 (4.26, 1.15-15.79, 0.03). CONCLUSIONS:
      Advanced age and diabetes predispose to neurocognitive dysfunction after CEA.
      These results are consistent with risk factors for neurocognitive dysfunction
      after coronary bypass and major stroke after CEA, supporting an underlying
      ischemic pathophysiology. Further work is necessary to determine the role these
      neurocognitive deficits may play in appropriately selecting patients for CEA.

PMID- 16639319
TI  - Suboptimal sphenoid and sellar exposure: a consistent finding in patients treated
      with repeat transsphenoidal surgery for residual endocrine-inactive
      macroadenomas.
AB  - OBJECTIVE: In a series of patients with residual endocrine-inactive macroadenomas
      who underwent repeat surgery, we assess possible reasons for prior subtotal
      removal, reoperative success, complication rates, and patient impressions.
      METHODS: All patients were identified who had a prior subtotal removal of an
      endocrine-inactive macroadenoma and were reoperated on for residual sellar tumor
      via an endonasal approach. RESULTS: Over 6 years, of 188 consecutive patients
      with endocrine-inactive adenomas, 30 (16%) had repeat surgery (age, 15-77 yr;
      median interval between surgeries, 25 mo; median follow-up, 20 mo). Maximal tumor
      diameter averaged 2.4 +/- 0.9 cm. At reoperation, a suboptimal bony exposure was
      seen in all 30 patients: at the sphenoid keel, the sella, or both in 97, 93, and
      90% of patients, respectively. Cavernous sinus invasion was seen in 16 (53%)
      patients and a fibrous/rubbery consistency in 12 (40%). Gross total tumor removal
      was achieved in 17 (57%) patients, including 12 of 14 (86%) with noninvasive
      tumors and 5 of 16 (31%) with invasive tumors, (P < 0.01). All six
      fibrous/rubbery but noninvasive tumors were totally removed. Of 16 patients with
      preoperative visual loss, 15 (94%) improved. Complications included one each of
      cerebrospinal fluid leak, delayed sinusitis, and new hypothyroidism. In 17
      patients with prior sublabial surgery who completed questionnaires, the second
      (endonasal) surgery was associated with an easier recovery, less pain, and better
      nasal airflow in 82, 88, and 93%, respectively (P < 0.0001). CONCLUSION: In
      patients with residual sellar endocrine-inactive adenomas, a suboptimal opening
      at the sphenoid keel or sella at the first surgery and a high proportion of
      fibrous/rubbery tumors likely contributed to prior subtotal removal of otherwise
      accessible tumor. With a wider exposure, most noninvasive tumors can be totally
      removed, whereas invasive tumors can be effectively debulked. An endonasal
      reoperation is well tolerated with a low complication rate.

PMID- 16639320
TI  - Socioeconomic costs of open surgery and gamma knife radiosurgery for benign
      cranial base tumors.
AB  - OBJECTIVE: The aim of this study was to evaluate the relative socioeconomic costs
      of benign cranial base tumors treated with open surgery and gamma knife
      radiosurgery. METHODS: In a retrospective study, we studied 174 patients with
      benign cranial base tumors, less than 3 cm in diameter (or volume less than 30
      ml), admitted in the past 5 years. Group A (n = 94) underwent open surgery for
      removal of the tumors, whereas Group B (n = 80) underwent gamma knife
      radiosurgery. The socioeconomic costs were evaluated by both direct and indirect
      cost. The direct costs comprised intensive care unit cost, ward cost, operating
      room cost, and outpatient visiting cost. The indirect costs included loss of
      workdays and mortality. The length of hospital stay, the number of lost workdays,
      surgical complications, mortality, and cost-effectiveness analysis were
      calculated as well. Student t test and chi test were used for statistical
      analysis. RESULTS: The mean length of hospital stay for open surgery was 18.2 +/-
      30.4 days including 5.0 +/- 14.7 days of intensive care unit stay and 13.0 +/-
      15.2 days of ward stay, P < 0.01. The mean hospital stay for gamma knife was 2.2
      +/- 0.9 days with no need of intensive care unit stay, P < 0.01. The mean loss of
      workdays for open surgery was 160 +/- 158 days and 8.0 +/- 9.0 days for gamma
      knife, P < 0.01. The gamma knife cost per hour (1435 US dollars) is higher than
      the open surgery cost per hour (450 US dollars), P < 0.01. The direct cost for
      gamma knife (9677 US dollars +/- 6700 US dollars) is higher than that for open
      surgery (5837 US dollars +/- 6587 US dollars), P < 0.01. Open surgery had more
      complication rates (31.2%) than gamma knife (3.8%). Open surgery had a mortality
      rate of 5.3%; there was no mortality for gamma knife. The indirect costs,
      including loss of workdays and mortality, were significantly higher for open
      surgery than for gamma knife, P < 0.01. Finally, the socioeconomic cost (34,453
      US dollars +/- 97,277 US dollars) is higher for open surgery than for gamma knife
      (10,044 US dollars +/- 7481 US dollars), P < 0.01. The CEA is significantly
      higher in gamma knife (3762 US dollars/quality-adjusted life year) than in open
      surgery (8996 US dollars/quality-adjusted life year), P < 0.01. CONCLUSION: Most
      of the socioeconomic loss with open surgery for benign cranial base tumors comes
      from the indirect costs of workdays lost and mortality. Gamma knife radiosurgery
      is a worthwhile treatment to our patients and to our society because it may
      shorten hospital stays and workdays lost and reduce complications, mortality,
      socioeconomic loss, and achieve better cost-effectiveness.

PMID- 16639321
TI  - Surgical strategies for recurrent craniofacial meningiomas.
AB  - OBJECTIVE: Recurrent cranial base meningiomas are among the most difficult tumors
      to treat surgically. Although they are histologically benign, these tumors often
      invade through the cranial base into the infratemporal and pterygopalatine
      fossae. We reviewed our experience with these tumors to describe the natural
      history of these lesions as well as provide a possible treatment paradigm.
      METHODS: Between 2000 and 2004, seven patients with meningiomas recurring through
      the cranial base into facial structures were treated at the University of Utah.
      Five patients were treated with transcranial approaches only, and two were
      treated with a combination of transcranial and transfacial approaches. RESULTS:
      The average age of our patients (6 women, 1 man) was 55 years. The original site
      of tumor was the sphenoid wing in four patients, the middle fossa in two
      patients, and the left frontal region in one patient. The average interval
      between the most recent tumor resection and recurrence into the face was 9.9
      years. The mean number of resections a patient underwent before invasion into the
      face was two. All but one patient had adjunctive therapy (including either
      radiation or chemotherapy) before recurrence into the face. CONCLUSION:
      Meningiomas that recur into facial structures present a unique treatment
      challenge. These lesions have a high rate of recurrence once they have invaded
      through the cranial base. Although combined approaches may be necessary to
      achieve a gross total resection, these lesions can often be reached using
      standard transcranial techniques.

PMID- 16639322
TI  - Subependymomas: an analysis of clinical and imaging features.
AB  - OBJECTIVE: Subependymomas are slow-growing, benign tumors usually found
      incidentally in the fourth ventricle at autopsy. They are typically associated
      with the ventricular system and become apparent clinically only when symptoms of
      hydrocephalus or mass effect develop. We review clinical, histological, and
      contemporary radiographic presentations of 16 subependymomas, including 2
      intraparenchymal tumors. METHODS: We retrospectively evaluated eight patients
      with pathologically proven subependymomas. Initial magnetic resonance imaging and
      magnetic resonance spectroscopy were reviewed when available. Imaging was also
      available on eight outside subependymoma cases reviewed by our radiology
      department. RESULTS: Twelve of these subependymomas were intraventricular, one
      was in the posterior fossa, two were intraparenchymal, and one was an
      intramedullary spinal cord tumor. These lesions were hypo- to hyperintense on T1-
      and T2-weighted magnetic resonance imaging, with minimal to moderate enhancement.
      Initial complaints included headache, seizures, tingling sensations, and
      weakness. Among our eight patients who underwent gross total resection with no
      adjuvant therapy, no recurrences have been noted on follow-up magnetic resonance
      imaging. CONCLUSION: Subependymomas are rare, representing only 0.51% of all
      central nervous system tumors operated on during an 8-year period at the
      University of Utah. Clinical symptoms were associated with tumor location:
      intracranial masses caused headaches, seizures, and neurological complaints, and
      spinal cord locations resulted in neurological deficit. The authors review the
      clinical presentation, management, and contemporary radiographic appearance of
      this rare tumor.

PMID- 16639323
TI  - Postoperative radiosurgery for malignant spinal tumors.
AB  - OBJECTIVE: Although, as a primary therapy, radiosurgery for spinal tumors is
      becoming more common in clinical practice and is associated with encouraging
      clinical results, we wanted to evaluate outcomes after radiosurgery in a series
      of postoperative patients. METHODS: We examined the medical records of 18
      postoperative patients who received radiosurgical treatment to their residual
      spinal tumors: metastatic carcinoma (10), sarcoma (3), multiple
      myeloma/plasmacytoma (4), and giant cell tumor (1). Marginal radiosurgical doses
      ranged from 6 to 16 Gy (mean, 11.4 Gy) prescribed to the 90% isodose line. All
      regions of the spine received treatment: 2 cervical, 15 thoracic, and 1
      lumbosacral. The volume of irradiated spinal elements receiving 30, 50, and 80%
      of the total dose ranged from 0.51 to 11.05, 0.19 to 6.34, and 0.06 to 1.73 cm,
      respectively. Treatment sessions (i.e., patient in to patient out of the room)
      varied between 20 and 40 minutes. Follow-up ranged from 4 to 36 months (median, 7
      mo). RESULTS: Even though significant doses of radiation were delivered to all
      regions of the spinal cord and nerve roots coincidentally involved in the
      treatments, only one patient in this series developed progressive symptoms
      possibly attributable to a toxic effect of the radiosurgery. Of those patients
      initially presenting with neurological deficits, 92% either remained
      neurologically stable or improved. CONCLUSION: Our observations suggest that
      radiosurgery as prescribed in this series of postoperative patients with residual
      spinal tumor is well-tolerated and associated with little to no significant
      morbidity.

PMID- 16639324
TI  - Posture-induced changes in intracranial pressure: a comparative study in patients
      with and without a cerebrospinal fluid block at the craniovertebral junction.
AB  - OBJECTIVE: The aim of this study was to determine posture-induced changes in
      intracranial pressure (ICP) when patients with hydrocephalus or idiopathic
      intracranial hypertension remained supine for 1 hour and then sat up and remained
      sitting for 3 hours. METHODS: Continuous ICP was monitored using a fiberoptic
      extradural sensor in: 1) 259 patients with hydrocephalus or idiopathic
      intracranial hypertension with free cerebrospinal fluid (CSF) flow through the
      craniovertebral junction and Sylvian aqueduct, 2) 20 patients with hydrocephalus
      secondary to aqueductal stenosis with free CSF flow through the craniovertebral
      junction, and 3) 97 patients with hydrocephalus associated with Chiari
      malformation. The maximum ICP difference (DeltaICP) was calculated as the
      difference between mean ICP in the supine position and minimum ICP value after
      changing body position. The mean ICP difference (DeltaICPmean) was calculated as
      the difference between the mean ICP in the supine position and the mean ICP while
      the patient was in a sitting position. RESULTS: In the complete sample, the
      median of DeltaICP was 13 mm Hg (interquartile range 10-17). The median of
      DeltaICPmean was 8 mm Hg (interquartile range 5-11). Both DeltaICP and
      DeltaICPmean were significantly greater in patients without obstruction in the
      craniospinal junction than in those with Chiari malformation (P = 0.005 and P =
      0.014, respectively). No differences were found in DeltaICP or DeltaICPmean
      between patients with Sylvian aqueduct stenosis and those without (P = 0.777 and
      P = 0.346, respectively). CONCLUSION: ICP reduction after a change in body
      position is significantly greater in patients with free CSF flow through the
      craniospinal junction than in those with Chiari malformation, indicating the
      difficulty or impossibility of CSF displacement into the spinal canal in the
      latter.

PMID- 16639325
TI  - Minimally invasive lateral mass screw fixation in the cervical spine: initial
      clinical experience with long-term follow-up.
AB  - OBJECTIVE: Lateral mass screw fixation of the subaxial cervical spine has been a
      major advancement for spinal surgeons. This technique provides excellent three
      dimensional fixation from C3 to C7. However, exposure of the dorsal spinal
      musculature can produce significant postoperative neck pain. The incorporation of
      a minimal access approach using tubular dilator retractors can potentially
      overcome the drawbacks associated with the extensive muscle stripping needed for
      traditional surgical exposures. METHODS: A retrospective analysis was performed
      on the first 18 patients treated using lateral mass screws placed in a minimally
      invasive fashion. All patients, except 2 who were lost to follow-up, had a 2-year
      minimum clinical follow-up. All patients had a computed tomography (CT) scan in
      the immediate postoperative period to check the positioning of implanted
      hardware. Operative time, blood loss, and complications were ascertained. Fusion
      was assessed radiographically with dynamic radiographs and CT scans. RESULTS:
      Sixteen of the 18 patients underwent successful screw placement. Two patients had
      the minimal access procedure converted to an open surgery because radiographic
      visualization was not adequate in the lower cervical spine. Six cases involved
      unilateral instrumentation and 10 had bilateral screws. A total of 39 levels were
      instrumented. There were no intraoperative complications, and follow-up CT scans
      demonstrated no bony violations except in cases where bicortical purchase was
      achieved. All patients achieved bony fusion. CONCLUSION: A minimally invasive
      approach using tubular dilator retractors can be a safe and effective means for
      placing lateral mass screws in the subaxial cervical spine. Up to two levels can
      be treated in this manner. This approach preserves the integrity of the muscles
      and ligaments that maintain the posterior tension band of the cervical spine but
      requires adequate intraoperative imaging.

PMID- 16639326
TI  - Clinical and radiological analysis of ossification of the anterior longitudinal
      ligament causing dysphagia and hoarseness.
AB  - OBJECTIVE: We retrospectively analyzed the clinical and radiological
      characteristics of ossification of the anterior longitudinal ligament (OALL).
      METHODS: Seventeen patients with OALL who underwent surgery between 1995 and 2003
      were reviewed. Symptomatic OALL was found in four patients. In 13 asymptomatic
      OALL patients who experienced mild to severe myelopathy, no swallowing difficulty
      was noted. The OALL was classified into three types by sagittal computed
      tomographic (CT) scans as segmental, continuous, and mixed and three types on
      axial CT scans as flat, nodular, and globular type. The thickness, numbers of
      involved vertebral bodies, and type and shape for symptomatic OALL were analyzed
      and compared with those for asymptomatic OALL. RESULTS: The mean thickness of
      13.5 mm for symptomatic OALL was significantly higher than that of 6.5 mm for
      asymptomatic OALL (P = 0.0009). A globular shape on axial CT was common for
      symptomatic OALL. There were no differences in the numbers of involved vertebral
      bodies and types of OALL on sagittal CT scans. Surgical excision of OALL was
      performed for all cases of symptomatic OALL. In 7 of 13 asymptomatic cases, OALL
      was simultaneously removed during anterior decompressive surgery for the
      associated pathology. CONCLUSION: The thickness on axial CT scans was an
      important contributing factor to dysphagia and hoarseness as was the shape of the
      OALL. The type of OALL on sagittal CT scans was similar to that of ossification
      of the posterior longitudinal ligament but did not influence the development of
      dysphagia. Good relief from symptoms was achieved for symptomatic OALL after
      removal of OALL.

PMID- 16639327
TI  - Cervical spine injuries in ocean bathers: wave-related accidents.
AB  - OBJECTIVE: Spine injuries can occur secondary to several aquatic recreational
      activities. A series of cases of patients who experienced cervical spine injuries
      secondary to ocean waves accidents is presented. A description and analysis of
      this kind of injury is performed. METHODS: Sixteen patients were treated from
      January 1999 to May 2005. The mechanism of accident, mechanism of injury,
      neurological status, radiographic findings, associated injuries, and treatment
      were analyzed. RESULTS: These injuries are common among older patients. More
      severe and devastating injuries occurred in young patients. The most common
      mechanism of injury is hyperextension associated to spondylosis, which usually
      caused central cord syndrome. CONCLUSION: Wave-related accidents in ocean bathers
      are secondary to lack of experience of swimming in the ocean and underestimating
      the danger of waves. Although different types of mechanism of injury occurred,
      hyperextension was the most common. High-risk patients are older people with
      preexisting cervical spondylosis.

PMID- 16639328
TI  - The Currarino triad: neurosurgical considerations.
AB  - OBJECTIVES: The Currarino triad, a relatively uncommon hereditary disorder, is
      often associated with tethered cord and anterior myelomeningocele. Little is
      known of the implications of these neuroanatomic malformations or of the
      neurosurgical attitude. The objective of this study is to identify the spinal
      cord and meningeal malformations associated with the Currarino triad and to
      discuss the risks and benefits of surgical intervention. METHODS: We analyzed the
      spinal cord malformations and the neurosurgical involvement with the Currarino
      triad by retrospective chart review. RESULTS: The Currarino triad neuroanatomic
      malformations were identified in five patients. The Currarino triad was
      associated with a tethered cord in three patients, a myelomeningocele in five
      patients, a syrinx in two patients, a fistula between the colon and spinal canal
      in two patients, and an Arnold-Chiari Type 1 malformation in one patient.
      CONCLUSION: Full spine imaging is required for all patients diagnosed with the
      Currarino triad. Magnetic resonance imaging of the head should be performed in
      every patient with neuroanatomic anomalies. Surgery of an anterior
      myelomeningocele is not necessarily indicated, only in the rare case in which the
      space-occupying aspect is expected to cause constipation or problems during
      pregnancy or delivery. Constipation directly after birth is seen in virtually all
      patients with the triad. Therefore, constipation cannot be used to diagnose a
      tethered cord syndrome nor indicate tethered cord release. Fistulas between the
      spinal canal and colon have to be operated on directly.

PMID- 16639329
TI  - Duration of in vivo antimicrobial activity of antibiotic-impregnated
      cerebrospinal fluid catheters.
AB  - OBJECTIVE: Shunt infection is a major neurosurgical concern even after 50 years
      of experience with shunt surgery. Staphylococcus species are responsible for the
      majority of cerebrospinal fluid shunt infections. In vitro, antibiotic
      impregnated cerebrospinal fluid shunt catheters (AIC) have demonstrated
      protection against multiple staphylococcus species and strains for reasonable
      periods. We aim to study the longevity of antimicrobial activity of AIC in vivo
      by using explanted catheters. METHODS: Twenty-five AICs (rifampicin [0.054%] and
      clindamycin [0.15%]) were explanted from 18 patients for noninfectious reasons,
      from 11 to 700 days postimplantation. The catheters were set up on standardized
      Staphylococcus aureus culture plates to detect antimicrobial activity. Unused
      fresh AIC segments were used as control in each culture plates. RESULTS: Fourteen
      explanted AICs demonstrated persistent antimicrobial activity against
      staphylococcal species. Antimicrobial activity was detected for a period of
      implantation up to 127 days. This is longer than that predicted by in vitro
      models. CONCLUSION: The persistent antimicrobial activity is likely to translate
      to ongoing in vivo antimicrobial protection. This period of protection exceeds
      that during which most shunt infections occur.

PMID- 16639330
TI  - Contribution of mural and bone marrow-derived neointimal cells to thrombus
      organization and wall remodeling in a microsurgical murine saccular aneurysm
      model.
AB  - OBJECTIVE: Endovascular occlusive therapy of human saccular cerebral artery
      aneurysms may fail because of thrombus recanalization and incomplete neointima
      formation. Bone marrow-derived progenitor cells may contribute to these
      processes, but their role in human saccular cerebral artery aneurysms and
      experimental aneurysm models remains unclear. METHODS: Experimental saccular
      aneurysms were constructed from syngeneic thoracic aortas transplanted end-to
      side to the abdominal aorta of Wistar rats (n = 14), C57/B6 mice (n = 13), ApoE
      mice (n = 7), reporter gene expressing ROSA mice (n = 7), and mice with labeled
      bone marrow (ROSA [n = 12] or green fluorescent protein [n = 3]). Magnetic
      resonance imaging or angiography was used to monitor patency of the experimental
      aneurysms. Histology and immunohistochemistry were used to study thrombus
      organization and neointima formation and X-gal staining and confocal microscopy
      to study the origin of neointimal cells. RESULTS: Experimental aneurysms
      developed luminal pads of neointimal hyperplasia or organizing thrombosis that
      became thicker and occluded partly the lumen at later time points during the
      first week. Reporter gene mice (ROSA) revealed that 42 to 81% (median, 58%) of
      neointimal hyperplasia/organizing thrombosis was derived from the experimental
      aneurysm wall. Bone marrow-derived neointimal cells were found in only 5 of 15
      mice (range, 11-73 per section; a median of 22 cells among a total of 2000-6000
      wall cells). CONCLUSION: Thrombus organizing or neointimal cells were mostly
      derived from the experimental aneurysm wall, with only a minor contribution from
      the bone marrow. In human saccular cerebral artery aneurysms, the contribution of
      bone marrow-derived neointimal cells might be more important and should be
      compared with that found in other experimental models used to develop
      endovascular therapies.

PMID- 16639331
TI  - Systemic administration of simvastatin after the onset of experimental
      subarachnoid hemorrhage attenuates cerebral vasospasm.
AB  - OBJECTIVE: Experimental evidence suggests that intercellular adhesion molecule-1
      mediated leukocyte extravasation contributes to the pathogenesis of cerebral
      vasospasm. Simvastatin, an HMG-CoA reductase inhibitor, decreases intercellular
      adhesion molecule-1 expression and competitively inhibits leukocyte intercellular
      adhesion molecule-1 binding. We hypothesized that administration of simvastatin
      after the onset of subarachnoid hemorrhage (SAH) would attenuate perivascular
      granulocyte migration and ameliorate cerebral vasospasm in a rabbit model of SAH.
      METHODS: New Zealand white rabbits (n = 15) underwent injection of autologous
      blood into the cisterna magna or sham surgery followed by subcutaneous injection
      of simvastatin (40 mg/kg) or vehicle 30 minutes, 24 hours, and 48 hours after SAH
      or sham surgery. Seventy-two hours later, basilar artery lumen diameter was
      measured by in situ perfusion/fixation and image analysis. CD-18 monoclonal
      antibody stained perivascular granulocytes and macrophages were counted under
      light microscopy. RESULTS: In vehicle treated rabbits, mean +/- standard
      deviation basilar artery diameter was reduced 3 days after SAH (n = 5) versus
      sham (n = 5) rabbits (0.49 +/- 0.08 mm versus 0.75 +/- 0.03 mm, P < 0.01). After
      SAH, mean +/- standard deviation basilar artery diameter was greater in
      simvastatin (n = 5) treated rabbits versus vehicle (n = 5) (0.63 +/- 0.04 mm
      versus 0.49 +/- 0.08 mm, P < 0.01). In vehicle treated rabbits, SAH resulted in
      an increase in the mean +/- standard deviation perivascular CD18 cell count (sham
      vehicle, 2.8 +/- 2; SAH-vehicle 90 +/- 27; P < 0.01). Subcutaneous administration
      of simvastatin attenuated this increase in perivascular CD18-positive cells after
      SAH (SAH statin, 41.6 +/- 13; SAH vehicle, 90 +/- 27; P < 0.001). CONCLUSION:
      Subcutaneous administration of simvastatin after the onset of SAH attenuates
      perivascular granulocyte migration and ameliorates basilar artery vasospasm after
      experimental SAH in rabbits. 5-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors, such as simvastatin, may potentially serve as agents in the
      prevention of cerebral vasospasm after SAH.

PMID- 16639332
TI  - Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide
      from a controlled-release polymer: toxicity in cynomolgus monkeys.
AB  - OBJECTIVE: Diethylenetriamine/nitric oxide (DETA/NO) has been shown to be an
      effective treatment for delayed posthemorrhagic vasospasm when released
      abluminally from ethylene-vinyl acetate copolymer (EVAc). However, the observed
      mortality associated with this drug warrants further investigation. To establish
      a maximum tolerable dose, this study evaluated the toxicity of DETA/NO released
      from EVAc in a dose-escalation series in cynomolgus monkeys (Macaca
      fascicularis). METHODS: DETA/NO was incorporated into EVAc at a 20:80 dry weight
      ratio (DETA/NO:EVAc). A total of 13 animals underwent a right frontotemporal
      craniotomy for placement of a single polymer delivering no drug (n = 3), 0.5 +/-
      0.1 mg/kg (n = 3), 0.9 +/- 0.1 mg/kg (n = 3), 1.9 +/- 0.2 mg/kg (n = 3), or a 3.2
      mg/kg dose (n = 1) into the subarachnoid space. RESULTS: The animal receiving the
      highest dose of DETA/NO (3.2 mg/kg) died 46 hours after surgery. The remaining
      animals survived for the planned duration of the study. One animal in the group
      receiving the 1.9 mg/kg dose experienced a seizure 25 hours after surgery and
      remained lethargic for 2 days before making a complete recovery. The remaining
      animals exhibited no adverse behavioral effects. Histopathological examination of
      brain tissue revealed hemorrhagic and ischemic changes at doses above 0.9 mg/kg.
      No evidence of vascular wall pathology or infection was observed in any animal.
      CONCLUSION: The greatest amount of DETA/NO safely delivered from EVAc copolymer
      to the subarachnoid space of the cynomolgus monkey is approximately 1.0 mg/kg.
      These findings show that continuous intracisternal delivery of DETA/NO is a safe
      and potentially effective strategy for prophylactic treatment of delayed cerebral
      vasospasm.

PMID- 16639333
TI  - Ultrastructure of perinidal capillaries in cerebral arteriovenous malformations.
AB  - OBJECTIVE: The ultrastructure of perinidal capillaries in cerebral arteriovenous
      malformations (AVMs) was examined to clarify their pathomorphological features.
      METHODS: Fifteen AVM specimens were dissected and divided into perinidal and
      intranidal groups and processed for ultrastructural study immediately after
      surgical removal. Eleven of the patients had presented with hemorrhage. Tissue
      from four normal controls was also studied. Electron microscopy was used to
      compare features of the blood-brain barrier and endothelial cells (ECs) of
      capillaries in perinidal, intranidal, and controls. RESULTS: Perinidal
      capillaries demonstrated abnormal ultrastructure of the blood-brain barrier with
      no basement membranes and astrocytic foot processes. ECs had fenestrated luminal
      surfaces. Large gaps were observed at endothelial intercellular junctions. ECs
      contained numerous filopodia, large numbers of cytoplasmic processes, numerous
      micropinocytotic vesicles, and the cytoplasm contained more filaments than those
      observed in controls. Pericytes were rich in pinocytotic vesicles, vacuoles, and
      filaments. Their processes were in close contact with ECs. Weibel-Palade bodies
      were present in perinidal ECs. CONCLUSION: The absence of blood-brain barrier
      components in perinidal capillaries may contribute to extravasation of red blood
      cells into the surrounding brain in the absence of major hemorrhage and explain
      the gliosis and hemosiderin occasionally seen around AVMs. Cellular
      differentiation and proliferation in perinidal capillaries should be included in
      a systematic study aimed at a better understanding of the mechanisms underlying
      the recurrence of surgically removed AVMs.

PMID- 16639334
TI  - Increased angiogenesis and angiogenic gene expression in carotid artery plaques
      from symptomatic stroke patients.
AB  - OBJECTIVE: Carotid plaque rupture is one of the main causes of stroke by creating
      cerebral emboli. The biochemical, molecular, and structural factors that promote
      carotid plaque rupture are not yet understood in detail. We hypothesize that
      increased microvascular blood flow within a carotid plaque might fissure the
      plaque, elevate local pressure, and promote plaque rupture. The aim of this study
      is to determine the role of angiogenesis and angiogenesis-related gene expression
      in symptomatic carotid plaque. METHODS: The present study evaluated the new
      vessel formation (using hematoxylin-eosin staining and CD34 immunohistochemistry)
      and angiogenic gene expression (using microarray and real-time polymerase chain
      reaction analysis) in carotid plaque specimens obtained during endarterectomy
      from 13 symptomatic stroke patients in comparison with eight asymptomatic
      patients. RESULTS: Symptomatic plaques showed significantly higher new vessel
      density in the fibrous cap (by 347%, P < 0.05) as well as in the plaque proper
      (by 196%, P < 0.05) compared with the asymptomatic plaques. The fibrous caps of
      the plaques were threefold thinner in the symptomatic patients when compared with
      the asymptomatic patients. In symptomatic plaque, gene expression analysis showed
      increased abundance of 31 transcripts known to promote angiogenesis and cell
      division compared with plaques of asymptomatic patients. CONCLUSION: This study
      suggests that angiogenic gene expression and the ensuing angiogenesis in the
      plaques might contribute to their destabilization and resulting symptoms.

PMID- 16639335
TI  - Ultrastructural study of the filum terminale and its elastic fibers.
AB  - OBJECTIVE: The filum terminale (FT) is a fibrovascular band involved in the
      pathophysiology of tethered cord syndrome (TCS). Its morphological and
      ultrastructural properties remain largely unknown even though they are thought to
      play a role in the generation of TCS in adult patients with normal level conus
      medullaris. MATERIALS AND METHODS: Twenty fresh adult human cadavers had their
      fila measured and removed. Transversal and longitudinal sections of the proximal,
      middle, and distal thirds of FT were submitted to light microscopy analysis with
      four different techniques. Five fila were selected for longitudinal and
      transversal scanning electron microscopy analysis. RESULTS: The bulk of the FT is
      composed of 5- to 20-microm thick longitudinal bundles of Type 1 collagen
      separated by 3- to 10-microm intervals, although capillaries and other elements
      may be present. A delicate (0.05-1.5 microm) meshwork of predominantly Type 3
      collagen transversal fibers connects these bundles. Abundant longitudinally
      oriented elastic and elaunin fibers are found inside collagen bundles. A complex
      tridimensional structure is evidenced on electron microscopy. CONCLUSION: The
      longitudinal arrangement of collagen bundles and the impressive amount of elastic
      and elaunin fibers should elicit considerable elastic properties to the FT. An
      altered elasticity mechanism has been proposed for TCS; further studies are
      needed with TCS patients to define whether the collagen structure, Type 1/Type 3
      proportion, or elastic fiber content are altered, which could lead to new
      histopathological definitions of TCS, helping neurosurgeons in the difficult
      management of TCS patients with normal level conus medullaris.

PMID- 16639336
TI  - Internet-based neuro-oncology patient recruitment.
AB  - THE PRIVACY RULE, as part of the Health Insurance Portability and Accountability
      Act, was implemented in 2003 as a response to public concern over potential
      abuses of private health information. Although the Privacy Rule was not intended
      to place limits on clinical research, its complexity has caused much confusion
      throughout the academic medicine and research communities. Many clinical and
      translational researchers have created clinical databases or human tissue banks
      to facilitate future research. Maintenance of such databases is considered a
      research activity under the Privacy Rule, and researchers are, therefore, subject
      to its regulations. We present a novel Internet-based method to generate and
      maintain a neurooncology patient registry and human tissue bank. Through our web
      site, we secure both Health Insurance Portability and Accountability Act research
      authorization and informed consent, enabling us to contact the treating physician
      for clinical data and pathological specimens. Considering the importance of
      continued use of clinical databases and tissue banks in the genetic era of
      medicine, our method offers one way for researchers to adapt to the changing
      world of clinical research.

PMID- 16639337
TI  - Adverse effects of antiretroviral drugs on HIV-1-infected and -uninfected human
      monocyte-derived macrophages.
AB  - Antiretroviral drugs approved for treatment of HIV-1 infection include nucleoside
      reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). Use of
      these drugs in combinations (highly active antiretroviral therapy) has delayed
      disease progression. However, long-term therapy is associated with potentially
      serious adverse effects. NRTIs are thought to contribute to these adverse effects
      via depletion of mtDNA. Inasmuch as macrophages (major targets for HIV-1) are
      highly metabolically active with large numbers of mitochondria, we investigated
      the effects of NRTIs (didanosine, stavudine, lamivudine, and zidovudine) on the
      viability and function of HIV-1-infected and -uninfected human monocyte-derived
      macrophages (MDMs). We demonstrate that the combinations didanosine/stavudine and
      lamivudine/zidovudine decrease mtDNA content in MDMs, with HIV-1-infected MDMs
      displaying a greater reduction than uninfected cells. This decrease correlated
      with decreased complement-mediated phagocytosis (C'MP) by MDMs, a process
      dependent on mitochondrial function. Inasmuch as PIs have previously been
      reported to interact with cellular proteases and given that cellular proteases
      are involved in the phagocytic process, we investigated the effects of the PI
      indinavir on C'MP. We demonstrate that indinavir augments C'MP by uninfected
      MDMs, but not HIV-1-infected MDMs. This study provides additional understanding
      on the effects of commonly used antiretroviral drugs on cellular immune function.

PMID- 16639340
TI  - Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin
      coadministration.
AB  - We studied the effect of rifampicin on steady-state pharmacokinetics of
      nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax)
      and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral
      treatment with nevirapine-containing regimens (200 mg twice daily). A baseline
      pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin
      (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic
      Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily.
      Liver function was monitored. Rifampicin caused significant reductions in Cmax
      (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of
      nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients.
      An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range
      in all 7 patients without exceeding the toxic level of 12 microg/mL. There were
      no clinical or laboratory adverse events. Our findings suggest that decreased
      bioavailability of nevirapine because of rifampicin coadministration could be
      overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily
      without short-term adverse events. Further studies to evaluate the long-term
      safety of higher dose of nevirapine are required.

PMID- 16639341
TI  - Coadministration of esomeprazole with fosamprenavir has no impact on steady-state
      plasma amprenavir pharmacokinetics.
AB  - OBJECTIVES: To evaluate the drug interaction between fosamprenavir (FPV) and
      esomeprazole (ESO) after repeated doses in healthy adults. METHODS: Subjects
      received ESO 20 mg once daily (qd) for 7 days followed by either ESO 20 mg qd +
      FPV 1400 mg twice daily (bid) or ESO 20 mg qd + FPV 700 mg bid + ritonavir (RTV)
      100 mg bid for 14 days in arms 1 and 2, respectively. After a 21- to 28-day
      washout, subjects received either FPV 1400 mg bid for 14 days (arm 1) or FPV 700
      mg bid + RTV 100 mg bid for 14 days (arm 2). Pharmacokinetic sampling was
      conducted on the last day of each treatment. RESULTS: Simultaneous
      coadministration of ESO 20 mg qd with either FPV 1400 mg bid or FPV 700 mg bid +
      RTV 100 mg bid had no effect on steady-state amprenavir pharmacokinetics. The
      only effect on plasma ESO exposure was a 55% increase in area under the plasma
      concentration-time curve during a dosing interval, tau[AUC0-tau], after
      coadministration of ESO 20 mg qd with FPV 1400 mg bid. CONCLUSIONS: FPV 1400 mg
      bid or FPV 700 mg bid + RTV 100 mg bid may be coadministered simultaneously with
      ESO without dose adjustment. However, the impact of staggered administration of
      proton pump inhibitors (PPI) on plasma amprenavir exposure is unknown at present.

PMID- 16639342
TI  - Antiviral activity of nucleoside analogues during short-course monotherapy or
      dual therapy: its role in preventing HIV infection in infants.
AB  - BACKGROUND: This is the first report on the preliminary efficacy of 4 different
      short-course nucleoside analogue regimens (stavudine [d4T], didanosine [ddI],
      d4T+ddI, and zidovudine [ZDV]) for the prevention of mother-to-child transmission
      of HIV-1 (MTCT) in a resource-limited setting. DESIGN: This prospective open
      label, randomized 4-arm study (May 1999 to May 2000) conducted in South Africa
      enrolled 373 women from 34 weeks of gestation; medication was continued through
      delivery and for 6 weeks to infants. MTCT rates were ascertained at birth, 6, 12,
      and 24 weeks of age. RESULTS: Mean maternal HIV-1 RNA levels decreased rapidly on
      treatment in all groups. At week 4, the mean decrease was 1.91 log10 copies/mL
      (c/mL) in the d4T+ddI group, 1.33 log10 c/mL in the ddI group, 1.12 log10 c/mL in
      the d4T group, and 0.76 log10 c/mL in the ZDV group. Among the 362 evaluable
      mother-infant pairs, 11 infants in the d4T group, 10 in the ddI group, 5 in the
      ZDV group, and 4 in the d4T+ddI group were infected by 24 weeks of age. Eleven
      infections occurred in utero. Treatment with d4T and ddI was not associated with
      lactic acidosis or hepatic steatosis. CONCLUSIONS: The abbreviated use of
      nucleoside analogues for the prevention of MTCT appears safe and effective.

PMID- 16639343
TI  - Prevalence of DSM-IV-defined mood, anxiety, and substance use disorders in an HIV
      clinic in the Southeastern United States.
AB  - BACKGROUND: Mood and anxiety disorders, particularly depression, and substance
      abuse (SA) commonly co-occur with HIV infection. Appropriate policy and program
      planning require accurate prevalence estimates. Yet most estimates are based on
      screening instruments, which are likely to overstate true prevalence. SETTING:
      Large academic medical center in Southeast. PARTICIPANTS: A total of 1,125
      patients, representing 80% of HIV-positive patients seen over a 2.5-year period,
      completed the Substance Abuse-Mental Illness Symptoms Screener, a brief screening
      instrument for probable mood, anxiety, and SA disorders. Separately, 148
      participants in a validation study completed the Substance Abuse-Mental Illness
      Symptoms Screener and a reference standard diagnostic tool, the Structured
      Clinical Interview for DSM-IV. METHODS: Using the validation study sample, we
      developed logistic regression models to predict any Structured Clinical Interview
      for DSM-IV mood/anxiety disorder, any SA, and certain specific diagnoses.
      Explanatory variables included sociodemographic and clinical information and
      responses to Substance Abuse-Mental Illness Symptoms Screener questions. We
      applied coefficients from these models to the full clinic sample to obtain 12
      month clinic-wide diagnosis prevalence estimates. RESULTS: We estimate that in
      the preceding year, 39% of clinic patients had a mood/anxiety diagnosis and 21%
      had an SA diagnosis, including 8% with both. Of patients with a mood/anxiety
      diagnosis, 76% had clinically relevant depression and 11% had posttraumatic
      stress disorder. CONCLUSIONS: The burden of psychiatric disorders in this mixed
      urban and rural clinic population in the southeastern United States is comparable
      to that reported from other HIV-positive populations and significantly exceeds
      general population estimates. Because psychiatric disorders have important
      implications for clinical management of HIV/AIDS, these results suggest the
      potential benefit of routine integration of mental health identification and
      treatment into HIV service sites.

PMID- 16639344
TI  - Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes
      CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of
      CYP3A as measured by a phenotyping drug cocktail in healthy volunteers.
AB  - OBJECTIVE: The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome
      P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail.
      Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and
      xanthine oxidase (XO) activities were evaluated using warfarin (WARF) + vitamin
      K, omeprazole (OMP), intravenous (IV) and oral (PO) midazolam (MDZ), and caffeine
      (CAF). DESIGN: : Open-label, multiple-dose, pharmacokinetic study in healthy
      volunteers. METHODS: Subjects (n = 14) simultaneously received PO WARF 10 mg,
      vitamin K 10 mg, OMP 40 mg, CAF 2 mg/kg, and IV MDZ 0.025 mg/kg on days (D) 1 and
      14, and PO MDZ 5 mg on D2 and D15. LPV/r (400/100 mg twice daily) was
      administered on D4-17. CYP2C9 and CYP2C19 activities were quantified by S-WARF
      AUC0-inf and OMP/5-hydroxy OMP ratio, respectively. CYP1A2, NAT-2, and XO
      activities were quantified by urinary CAF metabolite ratios. Hepatic and
      intestinal + hepatic CYP3A activities were quantified by IV (CL) and PO (CL/F)
      MDZ clearance, respectively. RESULTS: After LPV/r therapy, CYP2C9, CYP2C19, and
      CYP1A2 activity increased by 29%, 100%, and 43% (P = 0.001, 0.046, and 0.001),
      respectively. No changes were seen in NAT-2 or XO activity. Hepatic and
      intestinal + hepatic CYP3A activity decreased by 77% (P < 0.001) and 92% (P =
      0.001), respectively. CONCLUSION: LPV/r therapy results in modest induction of
      CYP1A2 and CYP2C9 and potent induction of CYP2C19 activity. Increasing doses of
      concomitant medications metabolized by these enzymes may be necessary. LPV/r
      inhibited intestinal CYP3A to a greater extent than hepatic CYP3A activity. Doses
      of concomitant CYP3A substrates should be reduced when combined with LPV/r,
      although intravenously administered compounds may require less of a relative dose
      reduction than orally administered compounds.

PMID- 16639345
TI  - A pharmacokinetic-pharmacodynamic model to optimize the phase IIa development
      program of maraviroc.
AB  - OBJECTIVES: To use a viral dynamics model to compare the effectiveness of in vivo
      viral inhibition of several doses of maraviroc (MVC;UK-427,857) and to use a
      modeling approach to support design decisions for a monotherapy study using
      various dosing regimens of maraviroc given with and without food. DESIGN: The
      pharmacokinetic-pharmacodynamic model was developed using clinical data from a
      first monotherapy study (study A4001007). This was a randomized, double-blind,
      placebo-controlled, multicenter study of maraviroc in 44 asymptomatic HIV-1
      infected patients. Patients received maraviroc under food restrictions at 25 mg
      once daily or 50, 100, or 300 mg twice daily, or placebo for 10 days. METHODS:
      Antiviral responses were assessed by measuring plasma HIV-1 RNA levels during
      screening, during randomization, at baseline, and daily during the 10 days of
      treatment and at days 11 to 15, 19, 22, 25, and 40. An integrated pharmacokinetic
      pharmacodynamic model was developed using the mixed effects modeling approach
      with patients' pharmacokinetic profiles on the last day of treatment, HIV-1 RNA
      levels over time, and the individual viral susceptibility. The parameters derived
      from the viral dynamic model were used to calculate average viral inhibition
      fraction, decay rate of actively infected cells, and basic reproductive ratio for
      each treatment group. Monte Carlo simulation was then used to determine the
      distribution of viral load change across simulated patients over time for each
      regimen to be studied in another monotherapy study, A4001015. RESULTS: The
      decline rate in the 300 mg twice daily group was comparable to that induced by
      potent protease inhibitor monotherapy, but was significantly slower than that in
      patients receiving combination therapy including both protease inhibitor and
      reverse transcriptase inhibitors. The efficacy of inhibition in vivo was
      estimated to range from 0.15 to 0.38 for the 25 mg once daily dose group and from
      0.88 to 0.96 for the 300 mg twice daily dose group. CONCLUSIONS: The model has
      aided the analysis and interpretation of the clinical data. The use of a model
      based approach for selecting doses can accelerate drug development by replacing
      some arms or trials with simulations.

PMID- 16639346
TI  - Cost-effectiveness of HIV rescreening during late pregnancy to prevent mother-to
      child HIV transmission in South Africa and other resource-limited settings.
AB  - A decision analysis model, from a health care system perspective, was used to
      assess the cost-effectiveness of HIV rescreening during late pregnancy to prevent
      perinatal HIV transmission in South Africa, a country with high HIV prevalence
      and incidence among pregnant women. Because new HIV prenatal prophylactic and
      pediatric antiretroviral therapy (ART) regimens are becoming more widely
      available, the study was carried out with different combinations of the two. With
      an estimated HIV incidence during pregnancy of 2.3 per 100 person-years, HIV
      rescreening would prevent additional infant infections and result in net savings
      when zidovudine plus single-dose nevirapine or single-dose nevirapine is used for
      perinatal HIV prevention, and ART was available to treat perinatally HIV-infected
      children. The cost savings were robust over a wide range of parameter values when
      ART was available to treat perinatally HIV-infected children but were more
      sensitive to variations around the baseline when ART was not available. The
      minimum time interval between the initial and repeat screens would be from 3 to
      18 weeks, depending on prophylactic and treatment regimens, for HIV rescreening
      to be cost saving. Overall, HIV rescreening late in pregnancy in high-prevalence,
      resource-limited settings such as South Africa would be a cost-effective strategy
      for reducing mother-to-child transmission.

PMID- 16639347
TI  - Increases in HIV-related sexual risk behavior among community samples of gay men
      in London and Glasgow: how do they compare?
AB  - OBJECTIVE: In this paper, we compare trends in sexual risk among gay men in the
      largest city in England (London) and the largest city in Scotland (Glasgow).
      METHODS: Self-complete questionnaires administered to representative samples of
      men visiting the commercial gay scenes in London and Glasgow in 1996, 1999, and
      2002 (N = 8247). RESULTS: Multivariate logistic regression was used to assess the
      trends in unprotected anal intercourse (UAI), UAI with partners of
      unknown/discordant HIV status, and UAI with more than 1 partner. Each increased
      significantly in 1999 and 2002 in London, but only in 2002 in Glasgow. Testing
      for HIV also increased significantly in London, but not in Glasgow. Overall, HIV
      testing levels were considerably lower in Glasgow (in 2002, 49.1% vs. 74.6% in
      London). Overall, sexual risk was higher in London, but UAI with partners of
      unknown/discordant HIV status was higher in Glasgow (in 2002, 27.4% vs. 21.3%).
      CONCLUSIONS: Although the same pattern of increase in HIV-related sexual risk
      behavior was apparent in the cities, differences in HIV testing and nonconcordant
      UAI suggest different HIV prevention needs and that targeted health promotion
      interventions are required in London and Glasgow. City-specific factors should be
      considered in the development of appropriate sexual health interventions.

PMID- 16639348
TI  - Changing behaviors and patterns among Cambodian sex workers: 1997-2003.
AB  - OBJECTIVE: Identify patterns and behaviors among direct and indirect female sex
      workers (DFSWs and IDFSWs, respectively) across Cambodia's 5 major cities from
      1997 to 2003. METHODS: Interviews with DFSWs and IDFSWs followed random selection
      from clusters in 5 cities. Individual characteristics and condom use with clients
      and other partners were assessed in univariate and multivariate analyses.
      RESULTS: From 1997 to 2003, consistent condom use with clients increased from 53%
      to 96% among DFSWs and from 30% to 84% among IDFSWs. DFSWs reported staying in
      their profession longer, had fewer clients per day, stayed longer in each
      brothel, were in increasingly larger brothels, and were tested more for HIV. For
      IDFSWs, there were significant changes: more reported practicing commercial sex
      and testing for HIV. In adjusted models, reported condom use with clients was
      significantly higher among DFSWs in later survey years (odds ratio [OR], 2.17)
      and who were never married (OR, 1.69), were in larger brothels (OR, 1.02), and
      charged more for sex (OR, 1.27), but lower for DFSWs with sweethearts (OR, 0.68)
      and who reported abnormal vaginal discharge (OR, 0.52). For IDFSWs, in the
      adjusted models, reported condom use with clients was higher in later years (OR,
      1.77) and for those reporting abnormal vaginal discharge (OR, 1.34) and HIV
      testing (OR, 1.46), and lower for those with sweethearts (OR, 0.49). CONCLUSIONS:
      From 1997 to 2003, Cambodian direct and indirect sex workers increased their use
      of condoms each year with commercial as well as noncommercial partners,
      contributing to the evidence that HIV prevention programs can produce significant
      changes in risk behaviors.

PMID- 16639349
TI  - A bridge over troubled waters: factors associated with non-injection drug users
      having injection drug-using sex partners.
AB  - OBJECTIVES: To examine factors associated with noninjectors having 1 or more
      injection drug users as sex partners. METHODS: We collected data as a part of the
      Self-Help in Eliminating Life Threatening Diseases study, a network-oriented
      experimental HIV prevention intervention. All eligible participants were
      administered a detailed face-to-face interview on their sociodemographic
      background, patterns of drug use, HIV prevention and risk behaviors, and social
      networks. The sample for these analyses consisted of 863 noninjectors, 97 of whom
      had 1 or more injection drug-using sex partners. RESULTS: Among the factors
      associated with an increased odds of having 1 or more injecting sex partners were
      long-term unemployment, increasing proportion of women in network (among male
      noninjectors), increasing number of recent sex partners (among former injectors),
      increasing number of injecting non-sex partners in the network, and increasing
      network size above 15. CONCLUSIONS: There are specific network characteristics
      associated with noninjectors having injecting sex partners.

PMID- 16639350
TI  - Genetic analysis of HIV-1 strains in rural eastern Cameroon indicates the
      evolution of second-generation recombinants to circulating recombinant forms.
AB  - The HIV-1 genetic diversity in most parts of Cameroon is well described and shown
      to be very broad. However, little is known about the composition of the HIV-1
      epidemic in the rural parts of eastern Cameroon. Therefore, we investigated 25
      specimens from this region for their subtypes in gag, pol, and env gene
      fragments. Along with genetic material of subtypes A1, C, G, CRF01_AE, CRF02_AG,
      and CRF11_cpx, we also identified a large number (24%, 6/25) of distinct env
      sequences within the subtype A radiation. CRF02_AG was the predominant genetic
      form in all genes studied. Half of the specimens studied were considered "pure"
      based on concordant subtypes in the genes studied, whereas the other half were
      unique recombinant forms (URFs). Except for 1 URF, all were second-generation
      recombinants (SGRs), 90% of which contained genetic material of CRF02_AG in at
      least 1 gene. Notably, we identified individuals from 3 different villages
      infected with CRF01_AE(gag)CRF02_AG(pol)A(env) strains, which is indicative of
      the evolution of this URF to a circulating recombinant form (CRF). In addition,
      we identified a CRF02_AG(pol)C(env) recombinant infecting a man and a woman
      living in the same village, suggesting horizontal transmission of this
      recombinant. The current study emphasizes the power of HIV-1 recombination
      through the generation of SGRs and the evolution of URFs into CRFs. These
      findings suggest that, in a region where a predominant HIV-1 strain cocirculates
      among several subtypes, recombination could eventually decrease the proportion of
      this strain over time, such as CRF02_AG in Cameroon.

PMID- 16639351
TI  - High prevalence of HIV infection associated with incarceration among community
      based injecting drug users in Tehran, Iran.
AB  - OBJECTIVES: To determine the prevalence and correlates of HIV-1 infection among
      community-based injecting drug users (IDUs) in Tehran, Iran. METHODS: In October
      2004, 213 IDUs were recruited from a drop-in center and its neighboring parks and
      streets in Tehran. Participants were interviewed using a structured questionnaire
      regarding their sociodemographics and HIV risk characteristics, and specimens of
      oral mucosal transudate were collected and tested for HIV-1 antibodies. Data were
      analyzed using chi and multiple logistic regression to estimate odds ratios (OR)
      and 95% confidence intervals (CI). RESULTS: The prevalence of HIV-1 infection was
      23.2% (48 of 207) among male injecting drug users. In the multivariable analysis,
      a history of shared drug injection inside prison (OR, 2.45; 95% CI, 1.01-5.97)
      and that of multiple incarcerations (OR, 3.13; 95% CI, 1.08-9.09) were associated
      with significantly higher prevalence of HIV-1 infection. CONCLUSIONS: The
      prevalence of HIV-1 infection has reached an alarming level among IDUs in Tehran,
      with incarceration-related exposures revealed to be the main correlates of HIV-1
      infection. Urgent and comprehensive harm reduction programs for drug users in
      prison and those in the community in Tehran are of prime importance to prevent
      further transmission of HIV infection.

PMID- 16639352
TI  - Immunosuppression, hepatitis C infection, and acute renal failure in HIV-infected
      patients.
AB  - BACKGROUND: Low CD4 cell counts predict HIV-related morbidity and mortality and
      may be associated with acute renal failure (ARF). OBJECTIVE: To estimate the
      effect of CD4 cell count on the incidence rate (IR) of ARF in ambulatory HIV
      infected patients with access to highly active antiretroviral therapy. METHODS:
      Observational clinical cohort of HIV-infected patients recruited from a
      university-based infectious diseases clinic, between 2000 and 2002, and followed
      up until December 31, 2002. Poisson log-linear regression models were used to
      calculate ARF IRs, IR differences, and IR ratios. RESULTS: The mean age of the
      705 study participants was 40 years, two thirds were male, and 61% were African
      American. Incidence rates of ARF were higher at lower CD4 cell counts and among
      patients who were coinfected with hepatitis C. Patients with hepatitis C
      coinfection who also had low CD4 cell counts had the highest adjusted IR of ARF.
      CONCLUSION: Immunosuppression and hepatitis C virus coinfection are associated
      with increased IRs of ARF in ambulatory HIV-1-infected patients.

PMID- 16639353
TI  - HIV-1 pol gene polymorphism and antiretroviral resistance mutations in drug-naive
      pregnant women in Yaounde, Cameroon.

PMID- 16639354
TI  - External validation of atazanavir/ritonavir genotypic score in HIV-1 protease
      inhibitor-experienced patients.

PMID- 16639355
TI  - Is "once-daily" regimen a key strategy for improving adherence to antiretroviral
      regimens?

PMID- 16639356
TI  - High sensitivity C-reactive protein and response to highly active antiretroviral
      therapy in women with HIV-1 infection.

PMID- 16639358
TI  - Genetic aspects of osteoporosis.

PMID- 16639359
TI  - Determinants of peak bone mass.

PMID- 16639360
TI  - Role of sex steroids in the regulation of bone metabolism in the adult skeleton.

PMID- 16639361
TI  - The hypothalamic control of bone mass, implication for the treatment of
      osteoporosis.

PMID- 16639362
TI  - Obesity and osteoporosis.

PMID- 16639363
TI  - [Nutrition and bone metabolism].

PMID- 16639364
TI  - Pathophysiology of RANK ligand (RANKL) and osteoprotegerin (OPG).

PMID- 16639365
TI  - The phosphatonins and the regulation of phosphate homeostasis.

PMID- 16639366
TI  - Parathyroid and autoimmunity.
AB  - Data in favor of chronic hypoparathyroidism as an autoimmune disease are
      examined. The article takes into consideration the different clinical forms,
      genetic patterns, histopathology, animal models, cellular immunity, circulating
      autoantibodies, target autoantigens, clinical manifestations, laboratory
      diagnosis and therapy. Furthermore, data on 71 Italian patients with chronic
      hypoparathyroidism are presented.

PMID- 16639367
TI  - Practical use of biochemical markers of bone turnover.

PMID- 16639368
TI  - Asymptomatic primary hyperparathyroidism: to treat or not to treat?

PMID- 16639369
TI  - Targeting treatment by the assessment of fracture risk.

PMID- 16639370
TI  - [Prevention and treatment of steroid-induced osteoporosis].

PMID- 16639371
TI  - Tumor bone disease.

PMID- 16639372
TI  - [New therapeutic approaches to osteoporosis].

PMID- 16639373
TI  - Combination therapy of osteoporosis.

PMID- 16639374
TI  - The management of secondary hyperparathyroidism.

PMID- 16639375
TI  - Engineering new bone with bone morphogenic proteins.

PMID- 16639387
TI  - Basketball not only for the tall.

PMID- 16639388
TI  - Altered glucose metabolism in obese youth.
AB  - Altered glucose metabolism in obese youth is associated with defects in insulin
      sensitivity and insulin secretion. Peripheral insulin resistance in obese youth
      is an early phenomenon, strongly associated with a pattern of lipid partitioning
      characterized by increased deposition of lipid in the visceral and
      intramyocellular compartments. This metabolic phenotype is further characterized
      by a relatively reduced adiponectin level and elevation of inflammatory
      cytokines. A reduced sensitivity of the beta cell for first phase insulin
      secretion results in impaired glucose tolerance, while reduced first and second
      phase beta cell sensitivity for insulin secretion results in overt type 2
      diabetes. Altered glucose metabolism in obese youth represents an element of the
      "insulin resistance syndrome", comprising obesity, dyslipidemia and hypertension.
      The dynamics of glucose tolerance status in these youngsters seems to be more
      rapid than in adults, thus representing a narrow window of opportunity for
      successful intervention to prevent diabetes.

PMID- 16639389
TI  - The emerging role of leptin in humans.
AB  - Leptin is an adipocyte-secreted hormone which plays a key role in energy
      homeostasis. Recent advances in leptin physiology have revealed that the main
      role of this hormone in humans is to signal energy availability in energy
      deficient states. Interventional studies in leptin deficient children and
      observational studies in normal girls and boys support a role for leptin as a
      permissive factor for the initiation of puberty in children. Moreover, recent
      "proof of concept" studies involving leptin administration to humans further
      support its critical role in regulating energy homeostasis, neuroendocrine and
      immune function as well as insulin resistance in states of energy/caloric
      deprivation. Leptin's potential role in the therapy of several disease states,
      including hypothalamic amenorrhea, anorexia nervosa and syndromes of insulin
      resistance is under intensive investigation.

PMID- 16639390
TI  - Wolfram/DIDMOAD syndrome, a heterogenic and molecularly complex neurodegenerative
      disease.
AB  - Wolfram syndrome (WS, OMIM 22233), is a rare, autosomal recessive, and
      neurodegenerative disease. The syndrome is also known as DIDMOAD, the acronym for
      diabetes insipidus diabetes mellitus, optic atrophy and deafness, which
      summarizes the main clinical features, among many others, in WS patients. The
      gene associated with the syndrome, called WFS1, is located in the 4p16.1 region.
      The WFS1 gene encodes for a transmembrane protein located in the endoplasmic
      reticulum. Although the function of the WFS1 protein remains unknown, it is
      thought to be related with intracellular calcium homeostasis. The pattern of
      presentation of WS suggested the existence of mitochondrial impairment.
      Mitochondrial DNA rearrangements were detected in some patients, thus confirming
      that hypothesis. Recently, a particular WS phenotype has been described linked
      with the long arm of chromosome 4. This work aims to summarize the current
      knowledge about this disease that causes a heterogeneous phenotype and has a
      complex molecular aetiology.

PMID- 16639391
TI  - Phenotypic variations in lipoid congenital adrenal hyperplasia.
AB  - Congenital lipoid adrenal hyperplasia (lipoid CAH) is an autosomal recessive
      disorder characterized by severe adrenal insufficiency and male sex reversal.
      Lipoid CAH is caused by mutations in two proteins that are essential for all
      steroid biosynthesis, the steroidogenic acute regulatory (StAR) protein and
      cytochrome P450scc. In this review, we discuss the clinical presentation and
      mechanisms behind the pathology of this fatal disorder.

PMID- 16639392
TI  - Psychological stress and new onset diabetes.
AB  - The precise role of psychological stress in mediating the development of various
      forms of diabetes is controversial. Recent data from animal studies and large
      epidemiological studies in humans provide strong linkage between psychological
      stress and diabetes. This review focuses on the current evidence linking T1DM and
      T2DM and psychological stress and illustrates the inherent difficulty in
      overcoming this controversial issue.

PMID- 16639393
TI  - [Assessment of image display of contrast enhanced T1W images with fat
      suppression].
AB  - The effects of imaging conditions and measures for their improvement were
      examined with regard to recognition of the effects of contrast on images when T1
      weighted imaging with selective fat suppression was applied. METHOD: Luminance at
      the target region was examined before and after contrast imaging using phantoms
      assuming pre- and post-imaging conditions. A clinical examination was performed
      on tumors revealed by breast examination, including those surrounded by mammary
      gland and by fat tissue. RESULTS: When fat suppression was used and imaging
      contrast was enhanced, the luminance level of fat tumors with the same structure
      as the prepared phantoms appeared to be high both before and after contrast
      imaging, and the effects of contrast were not distinguishable. This observation
      is attributable to the fact that the imaging conditions before and after contrast
      imaging were substantially different. To make a comparison between pre- and post
      contrast images, it is considered necessary to perform imaging with fixed
      receiver gain and to apply the same imaging method for pre- and post-contrast
      images by adjusting post-contrast imaging conditions to those of pre-contrast
      imaging.

PMID- 16639394
TI  - [Performance evaluation of computed tomography with equivalent resolution
      images].
AB  - A method of evaluating the performance of computed tomography (CT) with
      equivalent resolution images was investigated. Generally, in performance
      evaluations of CT, the resolution property is measured by the wire method, and
      the noise property is measured from noise images of a cylindrical water phantom.
      The signal-to-noise ratio (SNR) is then calculated for the integrated evaluation.
      Our proposed method enabled perceptual integrated evaluation by using equivalent
      resolution images created with frequency processing. The frequency-processing
      factor was calculated from the ratio of the modulation transfer factors of two
      models of CT, and the image of one of the two was processed by the factor.
      Because these processed images have resolution equivalent to images of the other
      CT, the perceptual evaluation with noise images becomes effective. In this
      investigation, images of a water phantom and a middle contrast resolution phantom
      were employed. Perceptual comparison of the amount of noise with equivalent
      resolution images could be performed easily, and effective performance evaluation
      was achieved. Therefore, our proposed method is useful for noise property and
      performance evaluation of CT.

PMID- 16639395
TI  - [Design and development of a secure DICOM-Network Attached Server].
AB  - It is not easy to connect a Web-based server with an existing DICOM server, and
      using a Web-based server on the Internet has risks. In this study, we designed
      and developed a secure DICOM-Network Attached Server (DICOM-NAS) through which
      the DICOM server in a hospital LAN was connected to the Internet. After receiving
      a client's image export request, the DICOM-NAS sent it to the DICOM server using
      the DICOM protocol. The server then provided DICOM images to the DICOM-NAS, which
      transferred them to the client, using HTTP. The DICOM-NAS plays an important role
      between the DICOM protocol and HTTP, and stores the requested images only
      temporarily. The DICOM server keeps all of the original DICOM images. If an
      unauthorized user attempts to access the DICOM-NAS, medical images cannot be
      accessed because images are not stored in the DICOM-NAS. Furthermore, the DICOM
      NAS has features related to reporting and MPR. Therefore, the DICOM-NAS does not
      require a large storage capacity, but can greatly improve information security.

PMID- 16639396
TI  - [Evaluation of low contrast resolution in cone beam CT using FPD].
AB  - We examined the low contrast resolution of cone beam CT (CBCT) equipped with an
      indirect-type flat panel detector and compared it with a commercial CT unit
      (Robusto) . In CBCT, the X-ray tube voltage of 110 kV was used, and in the
      Robusto, the usual 120 kV was used for examinations. The computed tomography dose
      index (CTDI) of the two systems was measured, and images scanned at about the
      same exposure to radiation were compared. The modulation transfer factors of the
      two systems were measured, and the convolution kernel that was the nearest to the
      characteristic of CBCT was chosen among kernels of the Robusto. A water phantom
      with a diameter of 200 mm was scanned, Wiener spectra were calculated, and signal
      to-noise ratios were compared. The low contrast resolution phantom was scanned,
      and detectability and contrast-to-noise ratio (CNR) were measured. In addition,
      we placed diluted contrast medium into a phantom, scanned the phantom, and
      measured the detectability and CNR. When the X-ray irradiation condition of CBCT
      was 75 mAs at 110 kV, the equal dose of radioactivity in the Robusto was 50 mAs
      at 120 kV. In the low contrast resolution phantom, detectability was 8.7%mm in
      CBCT, and 9.4%mm in the Robusto. In the low contrast resolution evaluation
      phantom, CNR was 1.39 in CBCT, and 2.69 in the Robusto. With diluted contrast
      medium, CNR was 1.28 in CBCT, and 0.60 in the Robusto. CBCT was inferior to the
      Robusto in a low contrast resolution phantom, but CBCT was superior to the
      Robusto using diluted contrast medium. We found that CBCT was useful in
      examinations using contrast media.

PMID- 16639397
TI  - Development of a method for reconstructing three-dimensional data from axial,
      sagittal, and coronal MR images.
AB  - Magnetic resonance (MR) imaging is useful for the diagnosis of brain atrophy and
      intracranial abnormalities. We have developed a method of automated volumetry to
      evaluate the degree of brain atrophy for the diagnosis of dementia. Whole-brain
      MR images with thin slices without gaps are required for segmentation and
      volumetry. However, obtaining such images requires that the patient remain at
      rest for a prolonged period, thereby reducing the throughput of MR imaging
      examinations. Therefore, a method is needed for the reconstruction of isotropic
      three-dimensional (3D) data using routine axial, sagittal, and coronal MR images
      with 30% gaps and measurement of brain volume. The method of reconstructing 3D
      data consists of four processes: 1) segmentation of the brain region on axial,
      sagittal, and coronal MR images using the region-growing technique; 2) setting
      data to a 3D domain; 3) registration by manual operation; and 4) interpolation
      between the data based on linear interpolation. In clinical MR images, the
      differences between this method and the conventional technique were less than
      10%. These results demonstrate that this technique is able to construct 3D data
      from axial, sagittal, and coronal MR images.

PMID- 16639398
TI  - [Development of computer-aided diagnostic system for detection of lung nodules in
      three-dimensional computed tomography images].
AB  - We have developed an automated computerized method for the detection of lung
      nodules in three-dimensional (3D) computed tomography (CT) images obtained by
      helical CT. In this scheme, a lung segmentation technique for the determination
      of the nodule search area is performed based on a gray-level thresholding
      technique. To enhance lung nodules, we employed the 3D cross-correlation method
      by using a 3D Gaussian template with zero-surrounding as a model of lung nodule.
      False positives are then eliminated by using a rule-base with 53 features. For
      further reduction of false positives, we performed linear discriminant analysis
      using these 53 features. The average number of false positives was 6.7 per case
      at a percent sensitivity of 85.0%. This computerized scheme will be useful to
      radiologists by providing a "second opinion" in case of possible early lung
      cancer.

PMID- 16639399
TI  - [Effect of vibration caused by time-varying magnetic fields on diffusion-weighted
      MRI].
AB  - Diffusion-weighted images (DWIs) with high b-factor in the body are often used to
      detect and diagnose cancer at MRI. The echo planar imaging (EPI) sequence and
      high motion probing gradient pulse are used at diffusion weighted imaging,
      causing high table vibration. The purpose of this study was to assess whether the
      diffusion signal and apparent diffusion coefficient (ADC) values are influenced
      by this vibration because of time-varying magnetic fields. Two DWIs were
      compared. In one, phantoms were fixed on the MRI unit's table transmitting the
      vibration. In the other, phantoms were supported in air, in the absence of
      vibration. The phantoms called "solution phantoms" were made from agarose of a
      particular density. The phantoms called "jelly phantoms" were made from agarose
      that was heated. The diffusion signal and ADC value of each image were compared.
      The results showed that the signal of DWI units using the solution phantom was
      not affected by vibration. However, the signal of DWI and ADC were increased in
      the low-density jelly phantom as a result of vibration, causing the jelly phantom
      to vibrate. The DWIs of vibrating regions such as the breast maybe be subject to
      error. A countermeasure seems to be to support the region adequately.

PMID- 16639400
TI  - Pro-tests for biomedical research.

PMID- 16639402
TI  - Motion perception is learned, not innate.

PMID- 16639403
TI  - LTP: AMPA receptors trading places.

PMID- 16639404
TI  - Making selective 'cone-ections'.

PMID- 16639405
TI  - Evaluating apples and oranges.

PMID- 16639406
TI  - Clearing obsolete NMDA receptors.

PMID- 16639407
TI  - Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q.
AB  - The phenotype of common variable immunodeficiency (CVID) is characterized by
      recurrent infections owing to hypogammaglobulinemia, with deficiency in
      immunoglobulin (Ig)G and at least one of IgA or IgM. Family studies have shown a
      genetic association between CVID and selective IgA deficiency (IgAD), the latter
      being a milder disorder compatible with normal health. Approximately 20-25% of
      CVID cases are familial, if one includes families with at least one case of CVID
      and one of IgAD. Nijenhuis et al described a five-generation family with six
      cases of CVID, five cases of IgAD, and three cases of dysgammaglobulinemia. We
      conducted a genome-wide scan on this family seeking genetic linkage. One interval
      on chromosome 4q gives a peak multipoint LOD score of 2.70 using a strict model
      that treats only the CVID patients and one obligate carrier with
      dysgammaglobulinemia as affected. Extending the definition of likely affected to
      include IgAD boosts the peak multipoint LOD score to 3.38. The linkage interval
      spans at least from D4S2361 to D4S1572. We extended our study to a collection of
      32 families with at least one CVID case and a second case of either CVID or IgAD.
      We used the same dominant penetrance model and genotyped and analyzed nine
      markers on 4q. The 32 families have a peak multipoint LOD score under
      heterogeneity of 0.96 between markers D4S423 and D4S1572 within the suggested
      linkage interval of the first family, and an estimated proportion of linked
      families (alpha) of 0.32, supporting the existence of a disease-causing gene for
      autosomal-dominant CVID/IgAD on chromosome 4q.

PMID- 16639408
TI  - Expanding the phenotype of craniofrontonasal syndrome: two unrelated boys with
      EFNB1 mutations and congenital diaphragmatic hernia.
AB  - Craniofrontonasal syndrome (CFNS, MIM 304110) is an X-linked craniofacial
      disorder that shows paradoxically greater severity in heterozygous females than
      in hemizygous males. Mutations have been identified in the EFNB1 gene that
      encodes a member of the ephrin-B family of transmembrane ligands for Eph receptor
      tyrosine kinases. Here, we describe two unrelated families, in both of which a
      mother and her son have proven mutations in EFNB1. The mothers have classical
      features of CFNS; although the sons have no major craniofacial features other
      than telecanthus, both had a congenital diaphragmatic hernia (CDH). Our cases
      represent the first in which CDH has been confirmed in males with mutations in
      EFNB1, highlighting an important role for signalling by ephrin-B1 in the
      development of the diaphragm.

PMID- 16639409
TI  - Localization of candidate regions for a novel gene for Kartagener syndrome.
AB  - Asymmetric positioning of internal organs is a characteristics of vertebrates.
      The normal left-right anatomic positioning, situs solitus, sometimes does not
      occur normaly, leading to laterality defects. Studies in animal models have shown
      that laterality decisions are mediated by a cascade of genes that lead to the
      asymmetric expression of Nodal, LEFTA, LEFTB and PITX2 in the lateral plate
      mesoderm. A search for mutations in genes implicated in left-right patterning in
      animal models allowed genes associated with heterotaxia defects in humans to be
      identified. However, these genes explain only a small percentage of human situs
      defects, suggesting that other genes must play a role. In this study, we report a
      consanguineous family of Turkish origin, composed of two unaffected parents and
      three children, two of whom presented Kartagener syndrome. On the basis of their
      family history, we hypothesize autosomal recessive mode of inheritance. A
      genotype analysis with polymorphic markers did not show linkage with any known
      genes or loci causing laterality disorders. Array CGH did not detect a
      duplication or microdeletion greater than 1 Mb as a possible cause. Genome wide
      screening using 10 K Affymetrix SNP chips was performed, allowing the
      identification of two regions of autozygosity, one in chromosome 1 and the other
      on chromosome 7. In the chromosome 1 locus, a strong candidate gene, encoding the
      kinesin-associated protein 3 (KIF3AP) was not mutated, based on SSCP/heteroduplex
      analysis and direct sequencing. These data provide a basis for the identification
      of a novel gene implicated in Kartagener syndrome.

PMID- 16639410
TI  - Germline fumarate hydratase mutations in patients with ovarian mucinous
      cystadenoma.
AB  - Germline mutations in the fumarate hydratase (FH) gene were recently shown to
      predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and
      renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the
      skin and the uterus, renal cell carcinoma, and uterine leiomyosarcoma. The aim of
      this study was to identify new families with FH mutations, and to further examine
      the tumor spectrum associated with FH mutations. FH germline mutations were
      screened from 89 patients with RCC, skin leiomyomas or ovarian tumors.
      Subsequently, 13 ovarian and 48 bladder carcinomas were analyzed for somatic FH
      mutations. Two patients diagnosed with ovarian mucinous cystadenoma (two out of
      33, 6%) were found to be FH germline mutation carriers. One of the changes was a
      novel mutation (Ala231Thr) and the other one (435insAAA) was previously described
      in FH deficiency families. These results suggest that benign ovarian tumors may
      be associated with HLRCC.

PMID- 16639411
TI  - Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions
      or depletion of mitochondrial DNA by a dHPLC-based assay.
AB  - ANT1, TWINKLE and POLG genes affect mtDNA stability and are involved in autosomal
      dominant PEO, while mutations in POLG are responsible for numerous clinical
      presentations, including autosomal recessive PEO, sensory ataxic neuropathy,
      dysarthria and ophthalmoparesis (SANDO), spino-cerebellar ataxia and epilepsy
      (SCAE) or Alpers syndrome. In this study, we report on the mutational analysis of
      ANT1, TWINKLE and POLG genes in 15 unrelated patients, using a dHPLC-based
      protocol. This series of patients illustrates the large array of clinical
      presentations associated with mtDNA stability defects, ranging from isolated
      benign PEO to fatal Alpers syndrome. A total of seven different mutations were
      identified in six of 15 patients (40%). Six different recessive mutations were
      found in POLG, one in TWINKLE while no mutation was identified in ANT1. Among the
      POLG mutations, three are novel and include two missense and one frameshift
      changes. Seventeen neutral changes and polymorphisms were also identified,
      including four novel neutral polymorphisms. Overall, this study illustrates the
      variability of phenotypes associated with mtDNA stability defects, increases the
      mutational spectrum of POLG variants and provides an efficient and reliable
      detection protocol for ANT1, TWINKLE and POLG mutational screening.

PMID- 16639412
TI  - Congenital bilateral absence of the vas deferens and recombination at CFTR.

PMID- 16639414
TI  - Dietary fatty acids and insulin secretion: a population-based study.
AB  - OBJECTIVE: Few epidemiological studies have examined the relationship of dietary
      fatty acids, especially MUFA, with the interrelation between insulin secretion
      and insulin resistance. We assessed the relation of dietary fatty acids with
      insulin secretion in a free-living population. DESIGN AND SETTING: This cross
      sectional, population-based study was undertaken in Pizarra, a small town in
      Spain. SUBJECTS AND METHODS: Anthropometrical data were collected for 1226
      persons selected randomly from the municipal census, 538 of whom (randomly
      chosen) were given a prospective, quantitative, 7-day nutritional questionnaire.
      The fatty acid composition of the serum phospholipids was used as a biological
      marker of the type of fat consumed. Beta-cell function (betaCFI) and insulin
      resistance index (IRI) were estimated by the Homeostasis Model Assessment.
      RESULTS: To determine which factors influence the variability of the betaCFI, we
      analyzed the variance of the betaCFI according to sex, the presence of
      carbohydrate metabolism disorders and the different components of the diet,
      adjusting the models for age, body mass index (BMI) and IRI. The dietary MUFA and
      polyunsaturated fatty acids (PUFA) contributed to the variability of the betaCFI,
      whereas only the proportion of serum phospholipid MUFA, but neither the saturated
      fatty acids nor the PUFA accounted for part of the variability of the betaCFI in
      a multiple regression analysis. CONCLUSION: The results of this population-based
      study corroborate the results of other clinical and experimental studies
      suggesting a favorable relationship of MUFA with beta-cell insulin secretion.
      SPONSORSHIP: Fondo de Investigacion Sanitaria, Junta de Andalucia and the
      Asociacion Maimonides.

PMID- 16639415
TI  - Definitions of childhood obesity: current practice.
AB  - OBJECTIVE: To review current practice in the definition of childhood obesity
      based on body mass index (BMI), in order to understand why the recommendations of
      the International Task Force on Obesity (IOTF) have not been fully adopted.
      DESIGN: Literature search using MEDLINE to identify papers on childhood obesity
      published in the first 4 months of 2005, and a cited reference search on the
      recommendations of the IOTF. RESULTS: Citations of the IOTF definition have
      increased since publication, but less than half of papers on childhood obesity
      published in the period used the definition. Most used the 95th centile of a
      national distribution to define obesity. CONCLUSIONS: Reasons for using centiles
      of a national distribution included the need for z-scores or centiles to define
      underweight or extreme obesity, not available in conjunction with the IOTF
      definition, inclusion of children under 2 years, and concerns about over- or
      underestimation of the prevalence of obesity. None of these preclude use of the
      principle underlying the IOTF definition, that of continuity with the adult
      definition of BMI of 30 kg/m2 or more. Adoption of either the IOTF definition or
      corresponding centiles of a national distribution would enable comparisons of
      prevalence between countries and over time.

PMID- 16639416
TI  - Overweight and obesity in Italian adults 2004, and an overview of trends since
      1983.
AB  - OBJECTIVE: Overweight has been increasing in several developed countries over the
      last few decades. No update information on the issue is available for Italy.
      DESIGN AND SETTING: We conducted a computer assisted personal in-house interview
      survey in March-April 2004, on a sample of 2932 Italian individuals (1407 men and
      1525 women) aged 18 years or over, representative of the general adult Italian
      population. Information on weight and height was self-reported. RESULTS: Overall,
      3.4% of the Italian adult population were underweight (< 18.5 kg/m2, 0.9% of men
      and 5.8% of women), 31.3% were overweight (25.0-29.9 kg/m2, 38.4% of men, 24.7%
      of women), and 8.2% were obese (> or = 30.0 kg/m2, 7.4% of men and 8.9% of
      women). Overweight or obesity was reported by 14.2% of subjects aged 18-24 years
      (20.6% of men and 7.6% of women). The highest proportions of overweight and obese
      subjects were in the 45-64 year age group for men (51.4% overweight, 10.0% obese)
      and in the > or = 65 year age group for women (38.8% overweight, 13.8% obese).
      Age- and sex-standardised prevalence of overweight or obesity was 36.0% for more
      educated subjects, and 54.0% for less educated ones. It was 32.3% in northern,
      44.3% in central and 47.0% in southern Italy. Overweight increased from 1983 to
      the early 1990s, and levelled off thereafter. Prevalence of obesity remained
      around 8-9% across the last 20 years. CONCLUSIONS: Trends of overweight and
      obesity in Italy are more favourable than in several developed countries. Still,
      approximately 15 million of Italian adults are overweight and 4 million obese.

PMID- 16639417
TI  - Sodium in the Finnish diet: II trends in dietary sodium intake and comparison
      between intake and 24-h excretion of sodium.
AB  - OBJECTIVE: To estimate cross-sectional and long-term dietary sodium intakes and
      sources in Finland, and to evaluate the validity of 48-h recall to assess sodium
      intake. DESIGN: Cross-sectional dietary surveys and food availability data (Food
      Balance Sheets). SETTING: Dietary surveys were carried out in Finland in 1992,
      1997 and 2002. Food availability data were collected from 1980 to 1999. SUBJECTS:
      A stratified random sample was drawn from the population register. The total
      number of participants in the three dietary surveys was 6730. In the subsample
      for urine collection, the number of participants was 879. INTERVENTIONS: Nutrient
      intakes were estimated on the basis of a 3-day food diary in 1992, a 24-h recall
      in 1997 and a 48-h recall in 2002. The 24-h urinary excretion of sodium was used
      to validate sodium intake. In addition, salt intake was estimated based on Food
      Balance Sheets. RESULTS: Sodium intake has slowly decreased since the early
      1980s. Reported daily sodium intake correlated significantly with sodium
      excretion. CONCLUSIONS: Sodium intake has decreased during the last two decades,
      but is still higher than the recommended daily intake. Sodium intake estimation
      based on dietary surveys and food availability data is a valid method provided
      that the food composition database is up to date and of good quality.
      SPONSORSHIP: All surveys were funded by the National Public Health Institute in
      Finland and the Ministry of Social Affairs and Health.

PMID- 16639418
TI  - Iron status and its association with pregnancy outcome in Korean pregnant women.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of iron
      deficiency anemia among Korean pregnant women and to assess the association
      between maternal hemoglobin (Hb) level and pregnancy outcome. DESIGN: A
      longitudinal study. SETTING: Ewha Womans University Hospital, Seoul, Korea.
      SUBJECTS: A total of 248 normal pregnant women of 24-28 weeks gestation and 190
      babies born to the pregnant subjects. METHODS: Maternal anthropometry, blood
      parameters and pregnancy outcomes were measured. RESULTS: Mean Hb, serum iron
      concentration, transferrin saturation and total iron binding capacity of the
      subjects were 11.4 g/dl, 89.4 microg/dl, 18.7% and 484.6 microg/dl, respectively,
      and 30.2% of the subjects were anemic judged by Hb concentration of <10.5 g/dl.
      When subjects were classified into tertile groups based on Hb levels, the lowest
      tertile (HbT1) group had significantly lower concentrations of cord serum iron
      and albumin than those in the highest tertile (HbT3) group. Newborn infants from
      the HbT1 group had significantly higher rates of preterm delivery, low birth
      weight and low Apgar scores than those in other groups. Logistic regression
      analysis showed that maternal serum albumin and Hb level were the most important
      predictive variables for low birth weight. CONCLUSIONS: A substantial proportion
      of Korean pregnant women were at risk of anemia. Infants born to women with a low
      Hb level showed a lower birth weight, height and Apgar scores.

PMID- 16639419
TI  - Modulation of cellular behavior by exogenous messenger RNA.

PMID- 16639420
TI  - Evolution in closely adjacent plant populations X: long-term persistence of
      prereproductive isolation at a mine boundary.
AB  - Flowering time differences between metal-tolerant and nontolerant populations of
      the grass Anthoxanthum odoratum growing across a mine boundary have persisted for
      over 40 years. These flowering time differences result in a high degree of
      prezygotic genetic isolation (isolation index=0.43) between the tolerant mine
      populations and nontolerant pasture populations. Previous work showing genetic
      determination of flowering time and a high turnover of individual plants argues
      strongly for the selective maintenance of this difference.

PMID- 16639421
TI  - Wolbachia infection influences the development of Culex pipiens embryo in
      incompatible crosses.
AB  - Wolbachia are maternally inherited endosymbiotic bacteria that infect many
      arthropod species and have evolved several different ways for manipulating their
      host, the most frequent being cytoplasmic incompatibility (CI). CI leads to
      embryo death in crosses between infected males and uninfected females, as well as
      in crosses between individuals infected by incompatible Wolbachia strains. In the
      mosquito Culex pipiens, previous studies suggested developmental variation in
      embryos stemming from different incompatible crosses. We have investigated this
      variation in different incompatible crosses. Unhatched eggs were separated into
      three classes based upon the developmental stage reached by the embryos. We found
      that incompatible crosses involving uninfected females produced only embryos
      whose development was arrested at a very early stage, irrespective of the
      Wolbachia variant infecting the male. These results differ from other host
      species where a developmental gradient that could reach late stages of
      embryogenesis or even living larvae was observed, and indicate a novel
      peculiarity of CI mechanism in C. pipiens. By contrast, all incompatible crosses
      with infected C. pipiens females produced embryos of all three classes. The
      proportion of embryo classes appeared to be associated with the strains involved,
      suggesting specific CI properties in different incompatible crosses. In addition,
      the contribution of parental genome was characterized in embryo classes using
      molecular markers for each chromosome. Embryo phenotypes appeared linked to the
      paternal chromosomes' contribution, as described in Drosophila simulans. However,
      this contribution varied according to maternal infection and independently of
      male factors.

PMID- 16639422
TI  - Patterns of hobo elements and their effects in natural populations of Drosophila
      melanogaster in Japan.
AB  - We studied the dynamics of hobo elements of Drosophila melanogaster in Japan with
      the goal of better understanding the invasion and evolution of transposons in
      natural populations. One hundred and twenty-six isofemale lines and 11 older
      stocks were tested for the presence and genetic phenotype of hobo elements. The
      oldest H strain, containing complete and deleted hobo elements, is Hikone-H
      (1957), but Hikone-R (1952) has no hobo-homologous sequences. The findings
      suggest that the hobo element invaded Japanese populations in the mid-1950s, at
      about the same time as the P element invasion in Japan. This chronology is
      consistent with the hypothesis of a recent worldwide hobo element invasion into
      D. melanogaster in the mid-1950s. In recently collected populations, H degrees
      strains (low hobo activity and high repression potency) are predominant, whereas
      H+ strains (high hobo activity and high repression potency) are predominant in
      the Sakishima Islands, the most southwestern islands of the Japanese archipelago.
      H' strains (high hobo activity and low repression potency) were first found in
      limited island populations. Japanese populations have not only full-size hobo
      elements and 1.5 kb Th elements but also characteristic deletion derivatives (1.6
      and 1.8 kb XhoI fragments) that we have named Jh elements. These results are
      consistent with transgenic experiments with complete hobo elements, in which
      populations evolved to H+ or H degrees via H', and in which 1.8 kb fragments
      appeared. We conclude that hobo elements invaded the central region of Japan,
      spread to the far islands, and that the invasion is currently at an intermediate,
      nonequilibrium stage.

PMID- 16639423
TI  - Is brain lactate metabolized immediately after neuronal activity through the
      oxidative pathway?

PMID- 16639424
TI  - VEGF protein associates to neurons in remote regions following cortical infarct.
AB  - Vascular endothelial growth factor (VEGF) is thought to contribute to both
      neuroprotection and angiogenesis after stroke. While increased expression of VEGF
      has been demonstrated in animal models after experimental ischemia, these studies
      have focused almost exclusively on the infarct and peri-infarct regions. The
      present study investigated the association of VEGF to neurons in remote cortical
      areas at three days after an infarct in primary motor cortex (M1). Although these
      remote areas are outside of the direct influence of the ischemic injury, remote
      plasticity has been implicated in recovery of function. For this study,
      intracortical microstimulation techniques identified primary and premotor
      cortical areas in a non-human primate. A focal ischemic infarct was induced in
      the M1 hand representation, and neurons and VEGF protein were identified using
      immunohistochemical procedures. Stereological techniques quantitatively assessed
      neuronal-VEGF association in the infarct and peri-infarct regions, M1 hindlimb,
      M1 orofacial, and ventral premotor hand representations, as well as non-motor
      control regions. The results indicate that VEGF protein significantly increased
      association to neurons in specific remote cortical areas outside of the infarct
      and peri-infarct regions. The increased association of VEGF to neurons was
      restricted to cortical areas that are functionally and/or behaviorally related to
      the area of infarct. There was no significant increase in M1 orofacial region or
      in non-motor control regions. We hypothesize that enhancement of neuronal VEGF in
      these functionally related remote cortical areas may be involved in recovery of
      function after stroke, through either neuroprotection or the induction of remote
      angiogenesis.

PMID- 16639425
TI  - Insulin reduces the BOLD response but is without effect on the VEP during
      presentation of a visual task in humans.
AB  - Functional magnetic resonance imaging (fMRI) based on blood oxygen level
      dependent (BOLD) contrast has become an invaluable tool in the assessment of in
      vivo neuronal activation. Quantification of the BOLD response is determined by
      the hemodynamic and metabolic changes that occur in response to brain
      stimulation. However, these changes may vary by changes in insulin, a hormone
      known to be vasoactive in some tissues. To determine if insulin has an effect on
      fMRI, we measured the BOLD response to a visual stimulus in five normal
      volunteers in which insulin was first suppressed and then brought to a high
      physiological concentration. In addition, we also examined the effect of insulin
      on activation of the visual cortex as measured by the visual-evoked potential
      (VEP). We found that the BOLD response measured in the presence of insulin (serum
      insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in
      its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100
      amplitude or latency acquired in the presence or absence of insulin in 28
      subjects using the same stimulus as that used for the fMRI experiments. Our
      observations suggest that insulin may have effects on cerebral blood flow and/or
      metabolism that affect the BOLD signal that are independent of its effects on
      neuronal activation identified by event related potentials (ERP). These findings
      highlight the complexity that must be considered when interpreting differences in
      fMRI responses between groups of subjects that differ in insulin concentration
      and/or insulin sensitivity.

PMID- 16639426
TI  - Efflux of drugs and solutes from brain: the interactive roles of diffusional
      transcapillary transport, bulk flow and capillary transporters.
AB  - We examined the roles of diffusion, convection and capillary transporters in
      solute removal from extracellular space (ECS) of the brain. Radiolabeled solutes
      (eight with passive distribution and four with capillary or cell transporters)
      were injected into the brains of rats (n=497) and multiple-time point experiments
      measured the amount remaining in brain as a function of time. For passively
      distributed compounds, there was a relationship between lipid:water solubility
      and total brain efflux:diffusional efflux, which dominated when k(p), the
      transcapillary efflux rate constant, was >10(0) h(-1); when 10(-1)<k(p)<10(-2) h(
      1) both diffusion and convection contributed, and when k(p)<10(-3) h(-1),
      convective efflux dominated. Para-aminohippuric acid (PAH) experiments (n=112)
      showed that PAH entered the brain passively, but had efflux transporters. The
      total efflux rate constant, k(eff), was the sum of a passive component
      (k(p)=0.0018 h(-1)), a convective component (k(csf)=0.2 h(-1)), and a variable,
      concentration-dependent component (k(x)=0 to 0.45 h(-1)). Compounds with cell
      membrane transporters had longer clearance half times as did an oligonucleotide,
      which interacted with cell surface receptors. Manipulation of physiologic state
      (n=35) did not affect efflux, but sucrose efflux half time was longer with
      pentobarbital anesthesia (24 h) than with no anesthesia or ketamine-xylazine
      anesthesia (2 to 3 h). These results show that solute clearance from normal brain
      ECS may involve multiple physiologic pathways, may be affected by anesthesia, and
      suggests that convection-mediated efflux may be manipulated to increase or
      decrease drug clearance from brain.

PMID- 16639427
TI  - Macrovascular contribution in activation patterns of working memory.
AB  - Brain activation maps of blood oxygenation level dependent (BOLD) signals during
      functional magnetic resonance imaging (fMRI) are sensitive to unwanted
      contributions from large vessels. Most BOLD-fMRI studies are based on a stimulus
      correlated modulation of the MRI signal amplitude that is sensitive to desired
      microvascular effects and unwanted macrovascular effects. Aiming to suppress
      macrovascular effects in activation patterns, this BOLD-fMRI study evaluates
      brain activation during a verbal working memory task (2-back) in healthy
      volunteers (n=18) using the amplitude and phase components of the MRI signal. The
      use of the first time point as a phase reference allowed us to eliminate phase
      wrapping artifacts and increase the statistical power of 'phase' activation, and
      this information was used to filter out voxels with significant macrovascular
      (i.e., draining and pial veins) contribution in 'amplitude' activation patterns.
      Across subjects, the task produced large modulations of the relative phase in the
      occipital, dorsolateral prefrontal, and parietal cortices, suggesting a common
      distribution of draining veins in these regions across subjects, and in the
      rostral frontal cortex, probably associated to stimulus-correlated motion of the
      head. The phase filtering method partially suppressed BOLD responses in the
      superior and lateral prefrontal, parietal, and occipital cortices; therefore the
      commonly reported brain activation in these cortices during working memory tasks
      may include significant macrovascular contributions. This study suggests that the
      phase information embedded in the MRI signal can be used to suppress unwanted
      macrovascular contributions in fMRI studies.

PMID- 16639428
TI  - Cholinesterase inhibitor blockade and its prevention by statins of sympathetic
      alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.
AB  - Cholinesterase inhibitors (ChEIs) have been used to treat Alzheimer's disease
      (AD). The efficacy of these drugs, however, is less than satisfactory. The
      possibility that ChEIs may have effects unrelated to ChE activity, such as
      negatively modulate neuronal nicotinic acetylcholine receptors (nAChRs) was
      evaluated. Since alpha7-nAChRs on cerebral perivascular sympathetic neurons
      mediate cerebral parasympathetic-nitrergic vasodilation, effects of
      physostigmine, neostigmine, and galantamine on alpha7-nAChR-mediated dilation in
      isolated porcine basilar arterial rings denuded of endothelium was examined using
      in vitro tissue bath technique. The results indicated that these ChEIs blocked
      vasodilation induced by choline (0.3 mmol/L), nicotine (0.1 mmol/L), and
      transmural nerve stimulation (TNS). The ChEI inhibition of dilation induced by
      TNS but not by choline or nicotine was prevented by atropine (0.1 micromol/L)
      pretreatment. Furthermore, using confocal microscopy, significant calcium influx
      induced by choline and nicotine in cultured porcine superior cervical ganglion
      (SCG) cells was attenuated by ChEIs. In alpha7-nAChR-expressed Xenopus oocytes,
      nicotine-induced inward currents were attenuated by alpha-bungarotoxin and ChEIs.
      Moreover, ChEI inhibition of nicotine- and choline-induced dilation was prevented
      by pretreatment with mevastatin and lovastatin (10 micromol/L), which did not
      affect ChEI inhibition of TNS-induced relaxation. These findings suggest that
      ChEIs inhibit the alpha7-nAChRs located on postganglionic sympathetic nerve
      terminals of SCG origin, causing a decreased release of nitric oxide in the
      neighboring nitrergic nerves and cerebral vasodilation. Inhibition of alpha7
      nAChRs leading to a potential cerebral hypoperfusion may contribute to the
      limitation of ChEIs and question the validity of using a ChEI alone in treating
      AD. The efficacy of ChEIs may be improved by concurrent use of statins.

PMID- 16639429
TI  - Statin therapy and autoimmune disease: from protein prenylation to
      immunomodulation.
AB  - Statins have been prescribed extensively for their cholesterol-lowering
      properties and efficacy in cardiovascular disease. However, compelling evidence
      now exists that statins also have extensive immunomodulatory properties that
      operate independently of lipid lowering. Consequently, much attention has been
      directed towards their potential as therapeutic agents for the treatment of
      autoimmune disease. Modulation of post-translational protein prenylation seems to
      be a key mechanism by which statins alter immune function. In this Review, the
      effect of statin therapy on immune function, and how this relates to the
      pathogenesis of autoimmune disease, is reviewed alongside current opinion of what
      the key biological targets of statins are.

PMID- 16639430
TI  - Microbicides and other topical strategies to prevent vaginal transmission of HIV.
AB  - The HIV epidemic is, by many criteria, the worst outbreak of infectious disease
      in history. The rate of new infections is now approximately 5 million per year,
      mainly in the developing world, and is increasing. Women are now substantially
      more at risk of infection with HIV than men. With no cure or effective vaccine in
      sight, a huge effort is required to develop topical agents (often called
      microbicides) that, applied to the vaginal mucosa, would prevent infection of
      these high-risk individuals. We discuss the targets for topical agents that have
      been identified by studies of the biology of HIV infection and provide an
      overview of the progress towards the development of a usable agent.

PMID- 16639431
TI  - Immunology and immunotherapy of Alzheimer's disease.
AB  - Although Alzheimer's disease is considered to be a degenerative brain disease, it
      is clear that the immune system has an important role in the disease process. As
      discussed in this Review, immune-based therapies that are designed to remove
      amyloid-beta peptide from the brain have produced positive results in animal
      models of the disease and are being tested in humans with Alzheimer's disease.
      Although immunotherapy holds great promise for the treatment of Alzheimer's
      disease, clinical trials of active amyloid-beta vaccination of patients with
      Alzheimer's disease were discontinued after some patients developed
      meningoencephalitis. New immunotherapies using humoral and cell-based approaches
      are currently being investigated for the treatment and prevention of Alzheimer's
      disease.

PMID- 16639433
TI  - Task-specific sensing--introduction.

PMID- 16639434
TI  - Benefits of optical system diversity for multiplexed image reconstruction.
AB  - Algorithms that use optical system diversity to improve multiplexed image
      reconstruction from multiple low-resolution images are analyzed and demonstrated.
      Compared with systems using identical imagers, systems using additional lower
      resolution imagers can have improved accuracy and computation. The diverse system
      is not sensitive to boundary conditions and can take full advantage of
      improvements that decrease noise and allow an increased number of bits per pixel
      to represent spatial information in a scene.

PMID- 16639435
TI  - Multiaperture imaging.
AB  - We study the reconstruction of a high-resolution image from multiple low
      resolution images by using a nonlinear iterative backprojection algorithm. We
      exploit diversities in the imaging channels, namely, the number of imagers,
      magnification, position, rotation, and fill factor, to undo the degradation
      caused by the optical blur, pixel blur, and additive noise. We quantify the
      improvements gained by these diversities in the reconstruction process and
      discuss the trade-off among system parameters. As an example, for a system in
      which the pixel size is matched to the diffraction-limited optical blur size at a
      moderate detector noise level, we can reduce the reconstruction root-mean-square
      error by 570% by using 16 cameras and a large amount of diversity. The algorithm
      was implemented on a 56 camera array specifically constructed to demonstrate the
      resolution-enhancement capabilities. Practical issues associated with building
      and operating this device are presented and analyzed.

PMID- 16639436
TI  - Adaptive flat multiresolution multiplexed computational imaging architecture
      utilizing micromirror arrays to steer subimager fields of view.
AB  - A thin, agile multiresolution, computational imaging sensor architecture, termed
      PANOPTES (processing arrays of Nyguist-limited observations to produce a thin
      electro-optic sensor), which utilizes arrays of microelectromechanical mirrors to
      adaptively redirect the fields of view of multiple low-resolution subimagers, is
      described. An information theory-based algorithm adapts the system and restores
      the image. The modulation transfer function (MTF) effects of utilizing
      micromirror arrays to steering imaging systems are analyzed, and computational
      methods for combining data collected from systems with differing MTFs are
      presented.

PMID- 16639437
TI  - Image reconstruction for thin observation module by bound optics by using the
      iterative backprojection method.
AB  - A method for reconstructing high-spatial-resolution images in an imaging system
      known as thin observation module by bound optics (TOMBO) is reported. We
      investigate a novel procedure combining a pixel-rearrangement method and
      iterative backprojection (IBP). Pixel rearrangement has been used until now in
      TOMBO, and IBP is a digital superresolution technique. We verify the
      effectiveness of the combined procedure with simulated and experimental results.

PMID- 16639438
TI  - Performance scaling in flat imagers.
AB  - A performance scaling formulation for flat form-factor cameras is introduced. The
      analysis follows from basic geometric and sensitivity constraints found in low
      profile imaging sensors. A capacity metric is proposed and used to estimate
      performance cost scaling as a function of the width-to-height aspect ratio in the
      optics of thin imagers. Two basic flat imaging sensor classes are considered-one
      folds the optical path of an annular telescope within the volume of a central
      obscuration, and the other uses spatial multiplexing and filtering across an
      array of low-resolution small cameras to generate an estimate of the high
      resolution image. Scaling trends are highlighted that enable general performance
      comparisons at the optical signal collection level, thereby providing conclusions
      that are independent of the computational aspects of any particular approach. The
      results indicate that thin imagers face significant costs in physical size and
      sampling requirements if they are to match the performance of conventional
      cameras in the basic parameters of field of view, resolution, dynamic range, and
      sensitivity.

PMID- 16639439
TI  - Enhancing form factor and light collection of multiplex imaging systems by using
      a cubic phase mask.
AB  - The bulky form factor of traditional optical sensors limits their utility for
      certain applications. Flat multiplex imaging-sensor architectures face the light
      gathering challenges inherent with small collection apertures. We examine a
      wavefront-coding approach wherein a cubic phase mask is used to increase the
      aperture sizes of multiplex imaging systems while maintaining the distance from
      the lens to the detector array. The proposed approach exploits the ability of
      cubic-phase-mask systems to operate over a large range of misfocus values. An
      exact expression for the optical transfer function of cubic-phase-mask systems is
      presented, and its misfocus-dependent spatial-filtering properties are described.
      Criteria for form-factor enhancement are assessed and trade-offs encountered in
      the design process are evaluated.

PMID- 16639440
TI  - Signal-to-noise analysis of task-based imaging systems with defocus.
AB  - We analyze the signal-to-noise ratio (SNR) of arbitrary imaging systems in the
      presence of defocus. The modulation transfer function (MTF) and the mean SNR are
      combined to calculate the spatial-frequency spectrum of the SNR (the spectral
      SNR). Computational imaging methods are used for extending the depth of field
      (DOF) of the system. The DOF of a task-specific imaging system is defined as the
      range of defocus that causes the spectral SNR to drop below a minimum value
      within a band of spatial frequencies of interest. We introduce the polar-SNR plot
      as a tool for visualizing the spectral SNR of defocused imaging systems with
      asymmetric pupil functions. As an example, we perform the analysis of an imaging
      system used for biometric iris recognition.

PMID- 16639441
TI  - Simultaneous measurement of temperature and pressure by a single fiber Bragg
      grating with a broadened reflection spectrum.
AB  - Simultaneous measurement of temperature and pressure with a single fiber Bragg
      grating (FBG) based on a broadened reflection spectrum is proposed and
      experimentally demonstrated. A novel double-hole structure of a cantilever beam
      is designed, and a FBG is affixed on the nonuniform strain area of the cantilever
      beam. The Bragg reflection bandwidth is sensitive to the spatially gradient
      strain but is free from the spatially uniform temperature. The wavelength peak
      shift and the bandwidth broadening of the FBG with a change of temperature and
      pressure allow for simultaneous discrimination between the temperature and the
      pressure effects. Standard deviation errors of 1.4 degrees C and 1.8 kPa were
      obtained with temperature and pressure ranges of 20 degrees C-100 degrees C and 0
      80 kPa, respectively. This novel and low-cost sensor approach has considerable
      potential applications for temperature-insensitive strain measurement.

PMID- 16639442
TI  - Multitaper scan-free spectrum estimation using a rotational shear interferometer.
AB  - Multitaper methods for a scan-free spectrum estimation that uses a rotational
      shear interferometer are investigated. Before source spectra can be estimated the
      sources must be detected. A source detection algorithm based upon the multitaper
      F-test is proposed. The algorithm is simulated, with additive, white Gaussian
      detector noise. A source with a signal-to-noise ratio (SNR) of 0.71 is detected
      2.9 degrees from a source with a SNR of 70.1, with a significance level of 10(
      4), approximately 4 orders of magnitude more significant than the source
      detection obtained with a standard detection algorithm. Interpolation and the use
      of prewhitening filters are investigated in the context of rotational shear
      interferometer (RSI) source spectra estimation. Finally, a multitaper spectrum
      estimator is proposed, simulated, and compared with untapered estimates. The
      multitaper estimate is found via simulation to distinguish a spectral feature
      with a SNR of 1.6 near a large spectral feature. The SNR of 1.6 spectral feature
      is not distinguished by the untapered spectrum estimate. The findings are
      consistent with the strong capability of the multitaper estimate to reduce out-of
      band spectral leakage.

PMID- 16639443
TI  - Analysis of slitless holographic spectrometers implemented by spherical beam
      volume holograms.
AB  - The analysis of a slitless volume holographic spectrometer is presented in
      detail. The spectrometer is based on a spherical beam volume hologram followed by
      a Fourier-transforming lens and a CCD. It is shown that the spectrometer is not
      sensitive to the incident angle of the input beam for the practical range of
      applications. A holographic spectrometer based on the conventional implementation
      is also analyzed, and the results are used to compare the performance of the
      proposed method with the conventional one. The experimental results are
      consistent with the theoretical study. It is also shown that the slitless volume
      holographic spectrometer lumps three elements (the entrance slit, the collimator,
      and the diffractive element) of the conventional spectrometer into one spherical
      beam volume hologram. Based on the unique features of the slitless volume
      holographic spectrometer, we believe it is a good candidate for portable
      spectroscopy for environmental and biological applications.

PMID- 16639444
TI  - Static two-dimensional aperture coding for multimodal, multiplex spectroscopy.
AB  - We propose a new class of aperture-coded spectrometer that is optimized for the
      spectral characterization of diffuse sources. The instrument achieves high
      throughput and high spectral resolution by replacing the slit of conventional
      dispersive spectrometers with a more complicated spatial filter. We develop a
      general mathematical framework for deriving the required aperture codes and
      discuss several appealing code families. Experimental results validate the
      performance of the instrument.

PMID- 16639445
TI  - Reconstruction of partially occluded objects encoded in three-dimensional scenes
      by using digital holograms.
AB  - We propose a task-specific digital holographic capture system for three
      dimensional scenes, which can reduce the amount of data sent from the camera
      system to the receiver and can effectively reconstruct partially occluded
      objects. The system requires knowledge of the object of interest, but it does not
      require a priori knowledge of either the occlusion or the distance the object is
      from the camera. Subwindows of the camera-plane Fresnel field are digitally
      propagated to reveal different perspectives of the scene, and these are combined
      to overcome the unknown foreground occlusions. The nature of the occlusions and
      the effect of subwindows are analyzed thoroughly by using the Wigner distribution
      function. We demonstrate that a careful combination of reconstructions from
      subwindows can reveal features that are not apparent in a reconstruction from the
      whole hologram. We provide results by using optically captured digital holograms
      of real-world objects and simulated occlusions.

PMID- 16639446
TI  - Multidimensional optical sensor and imaging system.
AB  - We describe a multidimensional optical sensor and imaging system (MOSIS). Using a
      time-multiplexing, polarimetric, and multispectral imaging system, we are able to
      reconstruct a fully integrated multidimensional scene. Image fusion is used to
      integrate the multidimensional images. The fused image contains more information
      than the single two-dimensional and three-dimensional (3D) images. The
      multidimensional imaging system utilizes polarimetric imaging, multispectral
      imaging, 3D integral imaging with time and space multiplexing, and 3D image
      fusion techniques to reconstruct the multidimensionally integrated scene. Optical
      experiments and computer simulations are presented.

PMID- 16639447
TI  - Parallel three-step phase-shifting digital holography.
AB  - We propose parallel three-step phase-shifting digital holography as a technique
      capable of noiseless instantaneous measurement of three-dimensional objects based
      on phase-shifting interferometry. The proposed digital holography carries out
      three-step phase shifting at the same time by using a phase-shifting array device
      located in the reference beam. The array device has a periodic three-step phase
      distribution, and its configuration is simplified compared with that required for
      conventional parallel phase-shifting digital holography. Therefore the optical
      system of the proposed parallel phase-shifting digital holography is more
      suitable for the realization of the proposed holography. We conduct both a
      numerical simulation and a preliminary experiment. The results of the simulation
      and experiment agree well with those of the conventional phase-shifting method
      and are superior to the results obtained by conventional digital holography by
      using the Fresnel transform alone. Thus the effectiveness of the proposed
      technique is verified.

PMID- 16639448
TI  - Three-dimensional vision from a multisensing mechanism.
AB  - An approach for sensing a three-dimensional (3D) object surface with an arbitrary
      geometric shape is presented. Combining two different 3D sensing mechanisms,
      point-array encoding based on affine transformation and fringe encoding based on
      phase mapping, we construct a mathematic model for 3D vision in which the point
      array encoding is initially applied to determine the fringe orders to create a
      control-vertex mesh with absolute coordinate values in 3D space. Then phase
      evaluation and phase unwrapping for fringe decoding is performed under the
      guidance of control-vertex mesh, leading to an absolute phase map and the
      corresponding range image of the test object. The computer simulations and
      experimental results are presented to demonstrate the theoretical prediction.

PMID- 16639449
TI  - Computational hyperspectral interferometry for studies of brain function: proof
      of concept.
AB  - Hyperspectral interferometric microscopy uses a unique combination of optics and
      algorithm design to extract information. Local brain activity rapidly changes
      local blood flow and red blood cell concentration (absorption) and oxygenation
      (color). We demonstrate that brain activity evoked during whisker stimulation can
      be detected with hyperspectral interferometric microscopy to identify the active
      whisker-barrel cortex in the rat brain. Information about constituent components
      is extracted across the entire spectral band. Algorithms can be flexibly
      optimized to discover, detect, quantify, and visualize a wide range of
      significant biological events, including changes relevant to the diagnosis and
      treatment of disease.

PMID- 16639450
TI  - Application of integrated sensing and processing decision trees for target
      detection and localization on digital mirror array imagery.
AB  - We demonstrate the applicability of integrated sensing and processing decision
      trees (ISPDTs) methodology to a set of digital mirror array (DMA) hyperspectral
      imagery. In particular, we demonstrate that ISPDTs can be used to detect and
      localize targets by using just a few DMA Hadamard frames, so that an entire
      hyperspectral data cube need not be collected to successfully perform the given
      task. This suggests that such an integrated sensing-processing suite may be
      appropriate for extremely time-sensitive pattern-recognition applications.

PMID- 16639451
TI  - Lightweight biometric detection system for human classification using
      pyroelectric infrared detectors.
AB  - We use pyroelectric detectors that are differential in nature to detect motion in
      humans by their heat emissions. Coded Fresnel lens arrays create boundaries that
      help to localize humans in space as well as to classify the nature of their
      motion. We design and implement a low-cost biometric tracking system by using off
      the-shelf components. We demonstrate two classification methods by using data
      gathered from sensor clusters of dual-element pyroelectric detectors with coded
      Fresnel lens arrays. We propose two algorithms for person identification, a more
      generalized spectral clustering method and a more rigorous example that uses
      principal component regression to perform a blind classification.

PMID- 16639452
TI  - Detection and tracking of the backreflection of potassium dihydrogen phosphate
      images in the presence or absence of a phase mask.
AB  - The potassium dihydrogen phosphate (KDP) crystals present in the final optics
      assembly at the National Ignition Facility (NIF) are used for conversion of an
      infrared laser light beam into an ultraviolet beam. The conversion is highest for
      a certain incident angle, the alignment of which is determined from the position
      of the backreflection beam, which exhibits a distinct characteristic shape. When
      a phase-plate device is introduced before the final assembly to increase the
      uniformity of the beam, the backreflection pattern changes drastically. The
      algorithm that is best for tracking the special-shaped beam is no longer suitable
      for tracking the phase-modified beam. We discuss our detection schemes for both
      situations. In particular, we demonstrate how the algorithm senses the modified
      beam by using a newly proposed criterion of correlation peak pedestal area and
      executes an alternate algorithm in real time without operator intervention. This
      new algorithm continuously tracks the beam pattern to guarantee reliable and
      repeatable sensing. Results from simulation and real-world implementation of the
      algorithm at the NIF facility are presented.

PMID- 16639453
TI  - Task-based imaging of colon cancer in the Apc(Min/+) mouse model.
AB  - Optical coherence tomography (OCT), laser-induced fluorescence (LIF), and laser
      scanning confocal microscopy (LSCM) were used for the task of multimodal study of
      healthy and adenomatous mouse colon. The results from each modality were compared
      with histology, which served as the gold standard. The Apc(Min/+) genetic mouse
      model of colon cancer was compared with wild-type mice. In addition, a special
      diet was used for the task of studying the origins of a 680 nm autofluorescent
      signal that was previously observed in colon. The study found close agreement
      among each of the modalities and with histology. All four modalities were capable
      of identifying diseased tissue accurately. The OCT and LSCM images provided
      complementary structural information about the tissue, while the autofluorescence
      signal measured by LIF and LSCM provided biochemical information. OCT and LIF
      were performed in vivo and nondestructively, while the LSCM and histology
      required extraction of the tissue. The magnitude of the 680 nm signal correlates
      with chlorophyll content in the mouse diet, suggesting that the autofluorescent
      compound is a dietary metabolite.

PMID- 16639454
TI  - Target-adaptive polarimetric synthetic aperture radar target discrimination using
      maximum average correlation height filters.
AB  - We report the development of a technique for adaptive selection of polarization
      ellipse tilt and ellipticity angles such that the target separation from clutter
      is maximized. From the radar scattering matrix [S] and its complex components, in
      phase and quadrature phase, the elements of the Mueller matrix are obtained.
      Then, by means of polarization synthesis, the radar cross section of the radar
      scatters are obtained at different transmitting and receiving polarization
      states. By designing a maximum average correlation height filter, we derive a
      target versus clutter distance measure as a function of four transmit and receive
      polarization state angles. The results of applying this method on real synthetic
      aperture radar imagery indicate a set of four transmit and receive angles that
      lead to maximum target versus clutter discrimination. These optimum angles are
      different for different targets. Hence, by adaptive control of the state of
      polarization of polarimetric radar, one can noticeably improve the discrimination
      of targets from clutter.

PMID- 16639455
TI  - Surface plasmon resonance sensor based on polarization interferometry and angle
      modulation.
AB  - A surface plasmon resonance (SPR) sensing technique based on polarization
      interferometry and angle modulation is presented. Its sensitivity is not a direct
      function of variation of reflection intensity, nor of phase shift. Rather, it is
      a function of the complex reflection coefficient. A three times standard
      deviation detection limit of 5.1 x 10(-7) refractive index units in a 2 Hz
      bandwidth is obtained with our experimental setup. A theoretical analysis shows
      that this technique can provide a wide linear measurement range. Moreover, the
      sensitivity is insensitive to the thickness of gold films over approximately 5
      nm. This SPR sensing technique is suitable for physical, chemical, and biological
      research.

PMID- 16639456
TI  - Inorganic immersion fluids for ultrahigh numerical aperture 193 nm lithography.
AB  - Immersion lithography has become attractive since it can reduce critical
      dimensions by increasing numerical aperture (NA) beyond unity. Among all the
      candidates for immersion fluids, those with higher refractive indices and low
      absorbance are desired. Characterization of the refractive indices and absorbance
      of various inorganic fluid candidates has been performed. To measure the
      refractive indices of these fluids, a prism deviation angle method was developed.
      Several candidates have been identified for 193 nm application with refractive
      indices near 1.55, which is approximately 0.1 higher than that of water at this
      wavelength. Cauchy parameters of these fluids were generated and approaches were
      investigated to tailor the fluid absorption edges to be close to 193 nm. The
      effects of these fluids on photoresist performance were also examined with 193 nm
      immersion lithography exposure at various NAs. Half-pitch 32 nm lines were
      obtained with phosphoric acid as the immersion medium at 1.5 NA. These fluids are
      potential candidates for immersion lithography technology.

PMID- 16639457
TI  - Liquid crystal polarization-converting devices for edge and corner extractions of
      images using optical wavelet transforms.
AB  - Optical properties of radially polarized light generated by liquid crystal (LC)
      polarization-converting devices with two LC molecular orientations (+/-180
      degrees and +/-90 degrees twist modes) are measured and the applicability to
      optical wavelet transforms (WTs) are discussed. It is found that the radially
      polarized lights in both the +/-180 degrees and +/-90 degrees twist modes can be
      regarded as wavelets. Based on the principle of WT, feature extractions of a
      simple binary image are carried out by applying the LC polarization-converting
      device to a shadow-casting system. Unique feature extraction properties of the
      shadow-casting system using the LC polarization-converting device and a LC
      microlens array are discussed. It is experimentally confirmed that edge and
      corner features are successfully extracted using the LC polarization-converting
      device with +/-180 degrees and +/-90 degrees twist modes, respectively.

PMID- 16639458
TI  - Investigation of thermal annealing of optical properties and residual stress of
      ion-beam-assisted TiO2 thin films with different substrate temperatures.
AB  - Titanium oxide films were prepared by ion-beam-assisted deposition on glass
      substrates at various substrate temperatures. The effect of the temperature of
      thermal annealing from 100 degrees C to 300 degrees C on the optical properties
      and residual stress was investigated. The influence on the stoichiometry and
      residual stress of titanium oxides deposited at different substrate temperature
      was discussed. The residual-stress was minimum and the extinction coefficient was
      maximum at an annealing temperature of 200 degrees C with a substrate temperature
      of 150 degrees C. However, when the substrate temperature was increased to 200
      degrees C and 250 degrees C, the residual stress was minimum and the extinction
      coefficient was maximum at an annealing temperature of 250 degrees C. The spectra
      of x-ray photoelectron spectroscopy reveal that the films lost oxygen and slowly
      generated lower suboxides at the annealing temperature at which the residual
      stress was minimum and the extinction coefficient was maximum. As the annealing
      temperature increased above the temperature at minimum stress, the lower
      suboxides began to capture oxygen and form stable oxides. TiO2 films deposited at
      substrate temperatures of 200 degrees C and 250 degrees C were more stable than
      films deposited at 150 degrees C.

PMID- 16639459
TI  - Optimization of deposition uniformity for large-aperture National Ignition
      Facility substrates in a planetary rotation system.
AB  - Multilayer coatings on large substrates with increasingly complex spectral
      requirements are essential for a number of optical systems, placing stringent
      requirements on the error tolerances of individual layers. Each layer must be
      deposited quite uniformly over the entire substrate surface since any
      nonuniformity will add to the layer-thickness error level achieved. A deposition
      system containing a planetary rotation system with stationary uniformity masking
      is modeled, with refinements of the planetary gearing, source placement, and
      uniformity mask shape being utilized to achieve an optimal configuration. The
      impact of improper planetary gearing is demonstrated theoretically, as well as
      experimentally, providing more comprehensive requirements than simply avoiding
      repetition of previous paths through the vapor plume, until all possible
      combinations of gear teeth have been used. Deposition efficiency and the impact
      of changing vapor plume conditions on the uniformity achieved are used to
      validate improved source placement. Uniformity measurements performed on a
      mapping laser photometer demonstrate nonuniformities of less than 0.5% for 0.75 m
      optics in a 72 in. (1.8 m) coating chamber.

PMID- 16639460
TI  - Time-multiplexed three-dimensional displays based on directional backlights with
      fast-switching liquid-crystal displays.
AB  - An autostereoscopic display using a directional backlight with a fast-switching
      liquid-crystal (LC) display was designed and fabricated to obtain a better
      perception of 3D images by enhanced resolution and brightness. A grooved light
      guide in combination with an asymmetric focusing foil was utilized to redirect
      the emitting cones of light to the left and right eyes, respectively. By
      designing the groove structures of the focusing foil with rotation from -1.5
      degrees to 1.5 degrees in the gradient and having the pitch ratio of the grooved
      light guide to the focusing foil of less than 3, the boundary angle then shifts
      from normal viewing and the moire phenomenon can be suppressed. Cross talk of
      less than 6% and a LC response time of faster than 7.1 ms further improve the
      stereoscopic image perception. Additionally, 2D-3D compatibility is provided.

PMID- 16639461
TI  - Direct fast method for time-limited signal reconstruction.
AB  - We consider reconstruction of signals by a direct method for the solution of the
      discrete Fourier system. We note that the reconstruction of a time-limited signal
      can be simply realized by using only either the real part or the imaginary part
      of the discrete Fourier transform (DFT) matrix. Therefore, based on the study of
      the special structure of the real and imaginary parts of the discrete Fourier
      matrix, we propose a fast direct method for the signal reconstruction problem,
      which utilizes the numerically truncated singular value decomposition. The method
      enables us to recover the original signal in a stable way from the frequency
      information, which may be corrupted by noise and/or some missing data. The
      classical inverse Fourier transform cannot be applied directly in the latter
      situation. The pivotal point of the reconstruction is the explicit computation of
      the singular value decomposition of the real part of the DFT for any order.
      Numerical experiments for 1D and 2D signal reconstruction and image restoration
      are given.

PMID- 16639462
TI  - Investigation of magnesium fluoride crystals for imaging acousto-optic tunable
      filter applications.
AB  - Results of an investigation of acousto-optic (AO) cells using single crystals of
      magnesium fluoride (MgF2) are presented. Two acousto-optic tunable filter (AOTF)
      cells for imaging application have been designed and tested in the visible and
      ultraviolet (UV) regions of the spectrum from 190 to 490 nm. The two imaging
      filters were developed by using the wide-angle AO interaction geometry in the
      (010) and (11 0) planes of the crystal. These filters were used to obtain
      spectral images at the shortest wavelengths achieved so far. Advantages and
      drawbacks of this crystal are discussed and photoelastic, acoustic, and AO
      properties of MgF2 are examined. The investigation confirmed that MgF2-based AOTF
      cells can be used in the deep UV region up to 110 nm.

PMID- 16639463
TI  - Spiking voltages for faster switching of nematic liquid-crystal light modulators.
AB  - Electrical address circuits developed for driving fast-switching ferroelectric
      liquid-crystal spatial light modulators (SLM) can be programmed to increase the
      speed of much slower responding nematic liquid-crystal SLMs. Using an addressing
      circuit that can switch as fast as 0.164 ms, voltages are programmed for values
      of phase that exceed the desired phase, and when the phase reaches the desired
      value, the voltage is switched to the required steady-state voltage. For a SLM
      that has a phase range of 3.5pi and that is programmed over a 2pi range,
      switching speed is reduced from 400 ms to between 71 and 77 ms. The speedup
      algorithm is applied to each pixel of the SLM together with a digital correction
      for a spatially nonuniform phase.

PMID- 16639464
TI  - Attenuation and impulse response for multiple scattering of light in atmospheric
      clouds and aerosols.
AB  - Model phase functions for atmospheric clouds and aerosols typically comprise a
      narrow forward lobe (corona), a broad diffuse background, and a narrow
      backscattering peak (glory), which can reach relatively high values, especially
      for polyhedral scattering particles, such as hexagonal ice columns and plates.
      The influence of these three major components on the asymptotic and transient
      attenuation of the scattered light is compared for several analytic phase
      functions to assess the dependence of radiative transfer in clouds and aerosols
      on the choice of phase function. The impulse response (temporal evolution of the
      angular intensity distribution) is sensitive to the higher moments of the phase
      function and could prove to be a useful technique for inferring the optical
      scattering parameters of clouds and aerosols.

PMID- 16639465
TI  - Airborne bacterial endospores detected by use of an impinger containing aqueous
      terbium chloride.
AB  - An experimental investigation is described of a terbium luminescence sensor for
      continuous collection and detection of bacterial endospores suspended in the
      atmosphere. A sensor is presented that continuously monitors and rapidly detects
      small concentrations of aerosolized bacterial endospores. The aerosol particles
      are collected by an impinger from which terbium dipicolinate photoluminescence is
      measured. A preliminary test of the sensor is described with Bacillus globigii
      endospores that were dispersed in an aerosol chamber. Another experiment is
      described showing that evaporation of water from the impinger limits operation
      time of the sensor to a few hours.

PMID- 16639466
TI  - Gaussian-reflectivity mirror resonator for a high-power transverse-flow CO2
      laser.
AB  - A Gaussian-reflectivity mirror resonator is proposed to achieve high-quality
      laser beams. To analyze the laser fields in a Gaussian-reflectivity mirror
      resonator, the diffraction integral equations of a Gaussian-reflectivity mirror
      resonator are converted to the finite-sum matrix equations. Consequently,
      according to the Fox-Li laser self-reproducing principle, we describe the mode
      fields and their losses in the proposed resonator as eigenvectors and eigenvalues
      of a transfer matrix. The conclusion can be drawn from the numerical results
      that, if a Gaussian-reflectivity mirror is adopted for a plano-concave resonator,
      a fundamental mode can easily be obtained from a transverse-flow CO2 laser and
      high-quality laser beams can be expected.

PMID- 16639467
TI  - Separation between the different fluxes scattered by art glazes: explanation of
      the special color saturation.
AB  - In a previous paper, the special visual appearance of art glazes was explained
      using the auxiliary function method (AFM) for solving the radiative transfer
      equation. Glazes are made of low concentrated colored scattering centers embedded
      in a transparent medium and the artist modulates the color by varying the number
      of glaze layers. A simple model of glazes and the new solving method have both
      been validated by comparison between flux measurements and modeling. The color of
      art glazes is analyzed here, and the study shows a spectacular maximum of
      saturation (purity) of the color that is never reached, to the best of our
      knowledge, with other techniques, such as pigment mixtures. This phenomenon is
      explained once more using the AFM that allows separation of the different
      contributions to the scattered fluxes. It is then shown that, on the one hand,
      single scattering never induces a maximum of saturation. On the other hand,
      multiple scattering has a typical increasing and decreasing behavior with an
      increasing number of glaze layers and thus participates to the maximum of
      saturation, just as the scattering by the diffuse base layer. A comparison
      between glazes and pigment mixtures, where the proportion of colored pigments
      with white pigments varies instead of the number of layers, shows that this
      maximum of saturation is much smaller with the second technique. To the best of
      our knowledge, we present a new development of the AFM that allows separation of
      the different origins of light scattering. We also show that it is possible to
      determine the optical properties of the scattering centers and of the base layer
      to create the required visual effect of a scattering medium.

PMID- 16639468
TI  - Frequency stabilization of an external cavity diode laser to molecular iodine at
      657.483 nm.
AB  - The saturation spectrum of the P(84) 5-5 transition of 127I2 at 657.483 nm is
      obtained with the third-harmonic demodulation method using an external cavity
      diode laser. The laser frequency is modulated by modulating the diode current
      instead of modulating the cavity length with a piezoelectric transducer (PZT).
      Current modulation allows a modulation frequency that is higher than PZT
      modulation. The signal-to-noise ratio of 1000 is better than previous results
      presented in the literature. The laser is frequency stabilized to the hyperfine
      component o of the P(84) 5-5 transition with a frequency stability of better than
      10 kHz (2.2 x 10(-11) relative stability).

PMID- 16639469
TI  - Finite-element-based photoacoustic tomography: phantom and chicken bone
      experiments.
AB  - We describe a photoacoustic image reconstruction algorithm that is based on the
      finite-element solution to the photoacoustic wave equation in the frequency
      domain. Our reconstruction approach is an iterative Newton method coupled with
      combined Marquardt and Tikhonov regularizations that can extract the spatial
      distribution of optical-absorption property in heterogeneous media. We
      demonstrate this algorithm by using phantom and chicken bone measurements from a
      circular scanning photoacoustic tomography system. The results obtained show that
      millimeter-sized phantom objects and chicken bones and/or joints can be clearly
      detected using our finite-element-based photoacoustic tomography method.

PMID- 16639470
TI  - Collaboration Between Dietetics and Dentistry: Dietetic Internship in Pediatric
      Dentistry.
AB  - The American Dietetic Association and the American Dental Association share a
      common interest in improving the health and quality of life of the population.
      Dental visits present an opportunity to identify nutrition-related issues for
      both the pediatric and adult population. Traditionally, dental and nutrition
      students have had little opportunity to learn and work together since little time
      was spent on nutrition in the dental curriculum. The purpose of this article is
      to describe the development of a new collaborative training experience for
      dietetic interns and pediatric dentistry residents. The oral health rotation for
      dietetic interns also has several objectives, including experience interacting
      with a culturally diverse population and participating in community nutrition
      education (Head Start). In its first 18 months, the collaborative program has
      been viewed as a success by the pediatric dentistry faculty and residents and the
      nutrition faculty and interns.

PMID- 16639471
TI  - Metabolic syndrome under fire: weighing in on the truth.
AB  - In the past two decades, the 'metabolic syndrome' has raised much clinical and
      research interest and remains a controversial topic. The constellation of
      commonly coexisting cardiovascular risk factors, now known as the metabolic
      syndrome, has had many definitions which has added to the confusion surrounding
      the syndrome. Recently, the controversy has been escalated by a joint statement
      from the American Diabetes Association and the European Association for the Study
      of Diabetes calling into question the existence and clinical utility of the
      metabolic syndrome as a discrete clinical entity. Despite the controversy, there
      is agreement that the risk factors of abdominal obesity, hypertension, elevated
      glucose and dyslipidemia commonly coexist in the same patient, and are important
      to identify when assessing an individual patient's risk. Therefore, whether the
      'syndrome' is a distinct clinical entity is not important. By definition, a
      syndrome is a group of signs or symptoms that commonly group together. It remains
      a useful clinical tool to raise awareness among health care professionals to look
      for 'nontraditional' cardiovascular risk factors, such as glucose intolerance or
      elevated waist circumference, in patients with other components of the syndrome,
      without negating the importance of identifying and treating the other
      'traditional' risk factors not identified in the syndrome. It also reminds
      clinicians of the importance of lifestyle interventions to treat all of the
      components of the syndrome. Therefore, the 'metabolic syndrome' continues to
      serve a useful clinical purpose to raise awareness among health care
      professionals and aid in identifying high-risk individuals.

PMID- 16639472
TI  - A novel, simple scale for assessing the symptom severity of atrial fibrillation
      at the bedside: the CCS-SAF scale.
AB  - BACKGROUND: The severity of symptoms caused by atrial fibrillation (AF) is
      extremely variable. Quantifying the effect of AF on patient well-being is
      important but there is no simple, commonly accepted measure of the effect of AF
      on quality of life (QoL). Current QoL measures are cumbersome and impractical for
      clinical use. OBJECTIVE: To create a simple, concise and readily usable AF
      severity score to facilitate treatment decisions and physician communication.
      METHODS: The Canadian Cardiovascular Society (CCS) Severity of Atrial
      Fibrillation (SAF) Scale is analogous to the CCS Angina Functional Class. The CCS
      SAF score is determined using three steps: documentation of possible AF-related
      symptoms (palpitations, dyspnea, dizziness/syncope, chest pain,
      weakness/fatigue); determination of symptom-rhythm correlation; and assessment of
      the effect of these symptoms on patient daily function and QoL. CCS-SAF scores
      range from 0 (asymptomatic) to 4 (severe impact of symptoms on QoL and activities
      of daily living). Patients are also categorized by type of AF (paroxysmal versus
      persistent/permanent). The CCS-SAF Scale will be validated using accepted
      measures of patient-perceived severity of symptoms and impairment of QoL and will
      require 'field testing' to ensure its applicability and reproducibility in the
      clinical setting. CONCLUSIONS: This type of symptom severity scale, like the New
      York Heart Association Functional Class for heart failure symptoms and the CCS
      Functional Class for angina symptoms, trades precision and comprehensiveness for
      simplicity and ease of use at the bedside. A common language to quantify AF
      severity may help to improve patient care.

PMID- 16639473
TI  - Skeletal muscle endurance and muscle metabolism in patients with chronic heart
      failure.
AB  - BACKGROUND: Alterations in skeletal muscle function are known to contribute to
      exercise intolerance in patients with chronic heart failure (CHF). OBJECTIVES: To
      evaluate whether muscle isometric endurance can be objectively measured and
      whether it is related to skeletal muscle metabolism in CHF. METHODS: Isometric
      endurance of the vastus lateralis, measured as time to fatigue (T(F)), was
      evaluated in 25 patients with CHF (55+/-8 years of age [mean +/- SD]) and 18
      healthy subjects (HS) (62+/-6 years of age [mean +/- SD]). Median frequency of
      surface electromyography was obtained from spectral analysis using a fast Fourier
      transformation. Citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (HADH),
      hexokinase (HK) and phosphofructokinase (PFK) activities were determined from the
      right vastus lateralis muscle. RESULTS: T(F) was lower in CHF patients than in HS
      (49+/-4 s and 80+/-7 s, respectively; P<0.01). Muscle fatigue was present at the
      end of the endurance test in both groups (median frequency breakpoint at mid
      exercise for both groups [P<0.05]). CS (P<0.01) and HK (P<0.01) activities were
      lower in CHF patients than in HS, but PFK activity was higher (P<0.05). T(F)
      correlated significantly with CS (r=0.50), HADH (r=0.42), PFK (r=-0.47) and HK
      (r=0.41) activities and the PFK/CS ratio (r=-0.39) when both groups were
      considered, and with HADH (r=0.47) and PFK (r=-0.57) activities for the CHF group
      alone (all P<0.05). CONCLUSIONS: These results suggest that isometric endurance
      of the vastus lateralis muscle is reduced in patients with CHF and that it is
      related to a reduced muscle oxidative capacity.

PMID- 16639474
TI  - N-terminal pro-brain natriuretic peptide and the timing, extent and mortality in
      ST elevation myocardial infarction.
AB  - AIMS: While natriuretic peptides have demonstrated diagnostic and prognostic
      potential in cardiac disorders, little is known about their relationship with the
      onset and quantification of myocardial infarction. The relationship of serial N
      terminal pro-brain natriuretic peptide (NT-proBNP) with duration from symptom
      onset, infarct size and prognosis in ST elevation myocardial infarction (STEMI)
      patients treated with primary percutaneous intervention was examined. METHODS AND
      RESULTS: Three hundred thirty-one STEMI patients in the COMplement inhibition in
      Myocardial infarction treated with Angioplasty (COMMA) trial, which evaluated
      pexelizumab versus placebo, were studied. NT-proBNP (pg/mL) was measured at
      randomization, 24 h and 72 h; creatine kinase-MB area under the curve was
      measured at 72 h; and QRS score was assessed at discharge. Prognosis was
      ascertained from the 90-day composite clinical outcome of death, shock, stroke
      and congestive heart failure. Multivariate logistical regression was used to
      adjust for baseline characteristics for models at randomization, 24 h and 72 h.
      NT-proBNP was higher in patients with longer time from symptom onset (P<0.001)
      and correlated with measures of infarct size, including the area under the curve
      (P<0.001) and QRS score (P<0.001). Patients reaching the primary end point had
      markedly higher NT-proBNP at each sampling period (P<0.001). NT-proBNP at all
      time points was the strongest independent predictor of the primary end point in
      the multivariate model: in the 24 h model, only age and 24 h NT-proBNP (C-index
      0.83); and only age, Killip class and NT-proBNP was in the 72 h model (C-index
      0.85). CONCLUSIONS: Higher NT-proBNP at 24 h correlated with larger infarct size
      and worse clinical outcomes. NT-proBNP at baseline, 24 h and 72 h after
      presentation with acute STEMI, is an independent predictor of a poor outcome and
      adds clinically useful prognostic information.

PMID- 16639475
TI  - Trends in five-year survival of patients discharged after acute myocardial
      infarction.
AB  - BACKGROUND: It has previously been shown that the increased use of therapeutic
      intervention may not reduce patient fatality if there is a simultaneous increase
      in case severity. The present study was designed to extend the relationship
      between case severity and therapeutic interventions to long-term survival in the
      same study population. OBJECTIVE: To compare five-year survival of patients
      discharged after acute myocardial infarction from 1984 to 1988 and from 1989 to
      1993, and to evaluate possible reasons for survival differences. METHODS: The
      present study was population-based. Survival time was determined by record
      linkage into the Canadian Mortality Database. Association of five-year survival
      with patient characteristics, in-hospital treatment and discharge medications was
      assessed by logistical regression analysis. Case severity was calculated as the
      probability of death within five years, given the patient profile and excluding
      any interventions. RESULTS: Between the two study periods, most patient
      characteristics and treatment intensity changed, but case severity for the study
      population remained constant. Five-year survival improved from 74.8% to 79.2%
      (P(chi2)=0.001). The improvement was adequately described by the combination of
      changes in patient profile and treatment without residual period effect
      (P(goodness-of-fit)=0.752). The treatments significantly associated with five
      year survival were coronary artery bypass graft surgery (OR 2.74; 95% CI 1.86 to
      4.05), percutaneous coronary intervention (OR 2.63; 95% CI 1.67 to 4.14) and
      thrombolysis (OR 1.98; 95% CI 1.50 to 2.62) during admission, as well as
      acetylsalicylic acid (OR 1.39; 95% CI 1.15 to 1.68) or beta-blocker (OR 1.60; 95%
      CI 1.34 to 1.92) prescription at discharge. CONCLUSIONS: Changes in patient
      profile did not affect long-term prognosis; instead, treatment modalities
      accounted for the observed improvement in five-year survival.

PMID- 16639476
TI  - Same-day transfer of patients with unstable angina and non-ST segment elevation
      myocardial infarction back to their referring hospital after angioplasty.
AB  - BACKGROUND: Recent evidence has shown the advantages of an early invasive
      strategy for patients with high-risk unstable angina (UA) and non-ST segment
      elevation myocardial infarction (NSTEMI). However, the number of beds available
      for postangioplasty monitoring limits the use of this approach at the Centre
      hospitalier universitaire de Sherbrooke (Fleurimont, Quebec). OBJECTIVES: To
      study the safety of a protocol allowing the same-day return of patients with UA
      or NSTEMI to their referring hospital after angioplasty at the Centre hospitalier
      universitaire de Sherbrooke. METHODS: From June 2001 to June 2003, of the 532
      patients with UA and NSTEMI who underwent percutaneous coronary intervention with
      planned same-day transfer back to their referring hospital, 419 consecutive
      patients who were eligible to return the same day were prospectively followed for
      24 h. RESULTS: Stents were used in 94.7% of patients and platelet glycoprotein
      IIb/IIIa receptor antagonists were used in 34.8% of patients. For 85% of
      patients, the femoral artery was used as the access route for percutaneous
      coronary intervention. The mean time that patients stayed in the hospital after
      angioplasty before returning to their referring centres was 4.4 h. No deaths,
      life-threatening arrhythmias or urgent revascularizations were reported during
      the 24 h postangioplasty follow-up period, but one patient had a major bleeding
      complication. During the study period, the mean angioplasty waiting time
      decreased from 5.7 days to 2.1 days. CONCLUSIONS: The protocol evaluated in the
      present article is safe. It frees more beds, thus reducing the waiting list and
      allowing patients with high-risk acute coronary syndromes without ST segment
      elevation from community hospitals to benefit from the advantages of an early
      invasive strategy.

PMID- 16639477
TI  - Detection of exercise-induced myocardial ischemia from symptomatology experienced
      during testing in men and women.
AB  - BACKGROUND AND OBJECTIVES: To examine the capacity of angina and related symptoms
      experienced during exercise-stress testing to detect the presence of ischemia,
      controlling for other clinical factors. METHOD: The authors undertook a
      prospective study of 482 women and 425 men (mean age 58 years) undergoing
      exercise stress testing with myocardial perfusion imaging. One hundred forty-six
      women and 127 men reported chest pain, and of these, 25% of women and 66% of men
      had myocardial perfusion imaging evidence of ischemia during testing. The present
      article focuses on patients with chest pain during testing. MAIN OUTCOME
      MEASURES: Outcome measures included chest pain localization, extension, intensity
      and quality, as well as the presence of various nonpain-related symptoms.
      Backward logistical regression analyses were performed separately on men and
      women who had experienced chest pain during testing. RESULTS: Men who described
      their chest pain as 'heavy' were 4.6 times more likely to experience ischemia
      during testing (P=0.039) compared with other men, but this pain descriptor only
      slightly improved accuracy of prediction beyond that provided by control
      variables. In women, several symptoms added to the sensitivity of the prediction,
      such as a numb feeling in the face or neck region (OR 4.5; P=0.048), a numb
      feeling in the chest area (OR 14.6; P=0.003), muscle tension (OR 5.2; P=0.013),
      and chest pain that was described as hot or burning (OR 4.3; P=0.014).
      CONCLUSIONS: A more refined evaluation of symptoms experienced during testing was
      particularly helpful in improving detection of ischemia in women, but not in men.
      Attention to these symptoms may favour timely diagnosis of myocardial perfusion
      defects in women.

PMID- 16639478
TI  - The use of lipid-lowering therapy for secondary prevention in patients undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: Recent literature suggests that lipid-lowering therapy may have an
      early beneficial effect among patients undergoing percutaneous coronary
      intervention (PCI) because the therapy decreases cardiac mortality, morbidity and
      possibly restenosis. OBJECTIVE: The primary objective of the present study was to
      determine the proportion of PCI patients receiving lipid-lowering therapy at a
      large, tertiary-care referral centre. METHODS: Patients undergoing a first PCI
      between August 2000 and August 2002 with corresponding inpatient medication
      information were included in the study. Patient demographics, procedural
      variables, and lipid-lowering and other evidence-based cardiac medication data
      were collected. A multiple logistical regression model was constructed to
      evaluate the factors associated with the use of lipid-lowering therapy. RESULTS:
      Of the 3254 cases included in the analyses, 52% were elective, 44% were urgent or
      salvage, and 4% were emergent. The mean patient age was 63 years, and 73% of
      patients were male. Over 76% of patients were receiving lipid-lowering therapy at
      the time of PCI. Patient use of other medications was as follows: acetylsalicylic
      acid in 96%, beta-blocker in 80% and angiotensin-converting enzyme inhibitor in
      59%. In the multiple regression analysis, variables significantly associated with
      lipid-lowering therapy use included hypercholesterolemia, beta-blocker use,
      angiotensin-converting enzyme inhibitor use, case urgency, prior coronary artery
      bypass graft surgery, age and sex. CONCLUSION: Lipid-lowering therapy use rates
      exceeded those previously reported in the literature. Women and patients
      undergoing elective procedures appear to be treated less often with lipid
      lowering therapy. There remains an opportunity to further optimize use in this
      high-risk cohort at time of PCI.

PMID- 16639479
TI  - Changes in cardiovascular deaths and hospitalization in Canada.

PMID- 16639480
TI  - A most unusual acute coronary syndrome.
AB  - A 60-year-old man, known for stable coronary artery disease, was admitted for
      suspected unstable angina. In the previous month, the patient presented with
      progressive dyspnea on light exertion. In the preceding four months, he had
      experience occasional episodes of flushing and diarrhea, and had inexplicably
      lost 22.7 kg. Night sweats and fever were absent. ST segment elevation in the
      inferior leads and ST segment depression in the precordial leads were documented
      during an episode of chest pain. The coronary angiogram showed diffuse disease
      with 70% stenosis of the left anterior descending coronary artery and 50%
      stenosis on the second diagonal (D(2)). An echocardiogram showed a patent foramen
      ovale. Balloon angioplasty and stenting were performed on the two lesions. Two
      days later, prolonged chest pain recurred. Cardiac catheterization was repeated
      and showed occlusive thrombus within the stent on the D(2). Angioplasty was
      repeated. Symptoms recurred 36 h later, with the electrocardiogram showing ST
      segment elevation. The first angiogram was reviewed and vasospasm was suspected
      on a branch of the D(2), on the second marginal and in the distal circumflex
      artery. The diagnosis of vasospastic angina was retained. Beta-blockers were
      replaced by high doses of a calcium channel blocker with an excellent clinical
      response. The case described is of a patient with an acute coronary syndrome,
      vasospastic angina, in-stent thrombosis and carcinoid disease. Coronary vasospasm
      was attributed to serotonin, which was secreted by the carcinoid tumour that
      reached an atherosclerotic coronary vasculature through a patent foramen ovale,
      thereby avoiding pulmonary inactivation.

PMID- 16639481
TI  - [The Italian Society of Rheumatology's registry for systemic autoinflammatory
      syndromes].

PMID- 16639482
TI  - [Carpal tunnel syndrome treatment].
AB  - Carpal tunnel syndrome, the most common peripheral neuropathy, results from
      compression of the median nerve at the wrist, and is a cause of pain, numbness
      and tingling in the upper extremities and an increasingly recognized cause of
      work disability. If carpal tunnel syndrome seems likely, conservative management
      with splinting should be initiated. Moreover, it has suggested that patients
      reduce activities at home and work that exacerbate symptoms. Pyridoxine and
      diuretics, since are largely utilised, are no more effective than placebo in
      relieving the symptoms. Non steroidal anti-inflammatory drugs and orally
      administered corticosteroids can be effective for short-term management (two to
      four weeks), but local corticosteroid injection may improve symptoms for a longer
      period. Injection is especially effective if there is no loss of sensibility or
      thenar-muscle atrophy and weakness, and if symptoms are intermittent rather than
      constant. If symptoms are refractory to conservative measures, the option of
      surgical therapy may be considered.

PMID- 16639483
TI  - [Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis,
      prevention and treatment].
AB  - Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory
      and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis
      (GIO) is the most common and serious side-effect for patients receiving GC. Loss
      of bone mineral density (BMD) is greatest in the first few months of GC use;
      fracture (Fx) risk is significantly increased at the spine and hip on doses even
      as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset
      of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP.
      General measures to reduce bone loss include use of the lowest effective dose;
      consideration of alternative routes of administration; adequate calcium and
      vitamin D supplementation. Today, results from large randomised controlled
      clinical trials provide evidence that bone loss and Fx may be prevented through
      the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34).
      Bisphosphonates (alendronate, risedronate) are first-choice therapy for the
      prevention and treatment of GIO; patients at high risk for Fx, for example those
      in post-menopausal status or aged > or =65 years and those with a prior fragility
      Fx, should be advised to start bone-protective therapy at the time of starting
      GC. Due to the prevalence of GC use, it is imperative that there be a greater
      awareness of GIO and of therapies that may be offered to patients both for
      prevention and treatment.

PMID- 16639484
TI  - [A comparison between the Simplified Disease Activity Index (SDAI) and the
      Disease Activity Score (DAS28) as measure of response to treatment in patients
      undergoing different therapeutic regimens].
AB  - OBJECTIVE: To compare the SDAI values to DAS28 scores in RA patients undergoing
      different DMARD regimens. METHODS: The SDAI is an unweighted numerical sum of
      five outcome parameters: tender and swollen joint count (based on 28-joint
      assessment), patient and physician global assessment of disease activity (visual
      analogue scale: 0-10 cm) and level of C-reactive protein (mg/dl). 80 patients
      (F/M 68/12; age between 20-68 years, median 52) with active rheumatoid arthritis
      were prospectively enrolled in the study. The patients were randomly assigned to
      one of four groups according to the therapeutic regimens: group I: Methotrexate
      (MTX) 15 mg/weekly + salazopyrin 2 g/daily; group II: MTX 15 mg/weekly +
      infliximab 3 mg/Kg at time 0, 2, 4 and every 8 weeks; group III: MTX 15 mg/weekly
      + etanercept 25 mg/twice weekly; group IV: MTX 15 mg/weekly + adalimumab 40
      mg/every other week. SDAI and DAS28 were determined at baseline and after 6
      months in each patient. Mean changes in SDAI values were compared to those
      detected in DAS 28 at baseline and after 6 months. RESULTS: SDAI and DAS 28 were
      found to be significantly correlated at baseline. Moreover, changes in SDAI over
      time paralleled those in DAS, and were found to be significantly correlated.
      CONCLUSIONS: SDAI is a valid measure of response to treatment in RA patients
      undergoing different therapeutic regimens.

PMID- 16639485
TI  - [The treatment of skin ulcers in systemic sclerosis: use of granulocyte-colony
      stimulating factor (G-CSF) in 26 patients].
AB  - OBJECTIVES: To verify the effectiveness of G-CSF in the treatment of non-healing
      skin lesions in SSc patients. METHODS: 26 SSc patients (23 F and 3 M, age 54 +/
      13,6 yrs) with skin ulcers were enrolled in a pilot study. Prior to the treatment
      with G-CSF, all ulcers failed to heal with conventional therapies carried out for
      a period of 1-5 years. All patients were treated with 5 microg/kg G-CSF
      subcutaneously for 5 days. Healing time, quality of wounds, VAS and HAQ-DI were
      used to evaluate the efficacy of the treatment. RESULTS: An improvement of skin
      ulcers was observed in 24/26 patients; in particular, 22/26 wounds completely
      healed, 2/26 showed a partial healing, in only 2 patients skin ulcers did not
      change during the 6-month follow-up. The quality of life improves as showed by
      VAS (from 88+/-13 to 55+/-28; p<.0001) and HAQ (from 2.12 +/-0.45 to 1.28+/-0.30;
      p<.0001). The eradication of pathogens from the infected ulcers was also observed
      in 12/12 patients; while no adverse side effects related to G-CSF were recorded.
      Our study suggests that G-CSF may be usefully employed in scleroderma skin ulcers
      refractory to conventional treatments.

PMID- 16639486
TI  - [Side effects of anti-TNFalpha therapy in juvenile idiopathic arthritis].
AB  - OBJECTIVES: To report adverse events registered in our population affected by JIA
      and treated with anti-TNFalpha blockers. METHODS: Ninety-five patients were
      enrolled to be treated with Etanercept, median age 14 years (range 4-34); median
      duration of therapy 12 months (range 1-40). 19 patients were also treated with
      MTX (median dose 12.5 mg/week). Fifty-six patients were enrolled to be treated
      with Infliximab associated with MTX (median dose of MTX 8.8 mg/week), median age
      23.2 years (range 7.8-34.9); median duration of therapy 20.1 months (range 1.4
      60.4). All adverse events were divided in definitely, probably and possibly
      related to the biologic agent. RESULTS: Side effects definitely related to
      Infliximab were the reactions to infusions and the Anti-dsDNA positivity. Side
      effects definitely related to Etanercept were severe headache and
      thrombocytopenia. Side effects probably correlated to both the biological agents
      were behavioural modifications and pain amplification syndrome. Probably
      correlated to the treatment with Etanercept was the onset of Crohn's disease in 3
      patients. Possibly correlated to the biological agents were the new onset or
      flare-up of Chronic Iridocyclitis and single cases of thyroideal cancer,
      hypoglossal nerve paralysis and a severe Cytomegalovirus pulmonary infection. No
      case of tuberculosis infection was registered during this study. CONCLUSIONS:
      Treatment with a TNFalpha antagonist seems to be associated with various adverse
      events. Some of them, like onset of Crohn's disease, behavioural modifications
      are unusual and others, like pain amplification syndrome were never described
      before. Children and young adults affected by JIA should be monitored very
      carefully so as to limit as much as possible the risk of serious side effects on
      anti-TNFalpha therapy.

PMID- 16639487
TI  - [18-month observational study on efficacy of intraarticular hyaluronic acid
      (Hylan G-F 20) injections under ultrasound guidance in hip osteoarthritis].
AB  - OBJECTIVE: To evaluate the efficacy and the tolerability of viscosupplementation
      (VS) with hyaluronic acid (Hylan GF 20) in a cohort of 36 patients affected by
      hip osteoarthritis through a 18 months follow-up. METHODS: Viscosupplementation
      was performed with an anteriorsagittal approach, under ultrasound guidance. 36
      patients were administered hyaluronic acid intraarticularly in the hip, with a
      unique injection of Hylan G-F20, which could be repeated after at least 3 months.
      Treatment efficacy was assessed by functional index WOMAC, pain evaluation on a
      visual analogue scale and NSAID consumption. All such parameters were recorded at
      the time of the first injection and then 3, 6, 9, 12 and 18 months later.
      RESULTS: Statistically significant reduction of all parameters was observed three
      months after the injection, and was still maintained at the timepoints 6, 9, 12
      and 18 months. No local side effects have been observed, nor systemic
      complications. CONCLUSIONS: Our data show that viscosupplementation is a
      promising approach for hip osteoarthritis, providing beneficial effects in a long
      term follow up. Yet, the topic deserves further and wider studies, so to define
      the number of injections to administer and suggest a fit interval between
      subsequent injections.

PMID- 16639488
TI  - [Migraine in SLE: role of antiphospholipid antibodies and Raynaud's phenomenon].
AB  - OBJECTIVES: To determine the role of antiphospholipid antibodies (aPL) and of
      Raynaud's phenomenon (RP) in the development of migraine in patients with
      systemic lupus erythematosus (SLE). METHODS: 50 unselected SLE patients and 20
      rheumatoid arthritis (RA) controls underwent an interview to define the presence
      of migraine according to the guidelines of the International Headache Society
      (1988). Serological tests for aPL were performed in all patients. SLE patients
      were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R
      /aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher's exact test, Chi
      square test and U Mann-Whitney test. RESULTS: SLE and RA patients were similar
      for demographic and clinical features; aPL positivity was found in a greater
      proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the
      50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine
      (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL
      positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on
      migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%)
      with respect to the patients negative for these two features (27%, p=0.0051,
      OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031,
      OR=6.2, CI:1.2-32). CONCLUSIONS: Migraine in SLE and RA associates with aPL
      positivity. The simultaneous presence of RP increases by 2,5 times the
      probability of having migraine, suggesting that cerebral vasospasm might be more
      common in patients with peripheral vasospasm, given the presence of aPL.

PMID- 16639489
TI  - [Case report: RAEB in a patient with rheumatoid arthritis treated with
      methotrexate and infliximab].
AB  - Anti TNF-alpha drugs seem to be the new frontier of Rheumatoid Arthritis (RA)
      therapy. The association infliximab methotrexate has been approved for the
      treatment of RA not responding to the classic therapy, but the short clinical
      experience in using antiTNF-alpha molecules brings to segnalation of new risks or
      adverse events. We describe a case of a patient, treated for many years with
      classic RA therapy, which developed a refractory anemia after treatment with
      association infliximab-methotrexate.

PMID- 16639490
TI  - [Idiopathic intervertebral disc calcification in children: the role of diagnostic
      imaging. A case report].
AB  - The idiopathic calcification of the intervertebral disc in childhood is a rare
      syndrome with unknown aetiology. This pathology is more frequent in males, with
      predominant localization to cervical spine. The natural evolution of the syndrome
      is the progressive and spontaneous resorption of the calcific deposit, with
      symptom regression. We report a case of an acute and worsening torticollis in a
      10-year-old child, with reference to a recent minor cervical distortion,
      resistant to analgesic treatment. X-ray evaluation, executed after a week from
      the appearance of torticollis, showed an oval calcification in the nucleus
      pulposus of the C6-C7 intervertebral disc. The CT and especially the MRI
      concurred to recognize a disc hernia and an adjacent osteo-ligamentous pathologic
      participation. In particular, MRI showed the adjacent vertebral spongy bone edema
      and the active enthesiopathy of the posterior longitudinal ligament.

PMID- 16639491
TI  - [The Italian contributions to the history of salicylates].
AB  - It is well-known that the modern history of salicylates began in 1899 when the
      compound acetylsalicylic acid was registered and introduced commercially as
      "aspirin" by the Bayer Company of Germany. As a matter of fact, however, remedies
      made from willow bark had been used to treat fever and rheumatic complaints at
      least since 1763, when Edward Stone described their efficacy against malarian
      fever. A number of Italian scientists made significant contributions during the
      long period of research leading up to the synthesis of acetylsalicylic acid and
      its widespread use in rheumatic diseases. In this paper we will review the
      contributions of some of these researchers, beginning with Bartolomeo Rigatelli,
      who in 1824 used a willow bark extract as a therapeutic agent, denominating it
      "salino amarissimo antifebbrile" (very bitter antipyretic salt). In the same
      year, Francesco Fontana described this natural compound, giving it the name
      "salicina" (salicin). Two other Italian chemists added considerably to current
      knowledge of the salicylates: Raffaele Piria in 1838, while working as a research
      fellow in Paris, extracted the chemical compound salicylic acid, and Cesare
      Bertagnini in 1855 published a detailed description of the classic adverse event
      associated with salicylate overdoses--tinnitus--which he studied by deliberately
      ingesting excessive doses himself. Bertagnini and above all Piria also played
      conspicuous roles in the history of Italy during the period of the Italian
      Risorgimento, participating as volunteers in the crucial battle of Curtatone and
      Montanara during the first Italian War of Independence.

PMID- 16639492
TI  - Phase II trial of temozolomide plus marimastat for recurrent anaplastic gliomas:
      a relationship among efficacy, joint toxicity and anticonvulsant status.
AB  - PURPOSE: Since anaplastic gliomas (AG) depend on matrix metalloproteinases for
      tumor cell invasion and angiogenesis, we undertook this phase II study to
      evaluate the matrix metalloproteinase inhibitor marimastat (MT), combined with
      the alkylator temozolomide (TMZ) in patients with recurrent AG, looking for
      improved outcomes. PATIENTS AND METHODS: Patients were treated every 28 days with
      TMZ at 150-200 mg/m2 once daily on days 1-5 and MT at 25 mg twice daily on days 8
      28. Results were compared to our database of anaplastic glioma patients treated
      at recurrence. A subanalysis of the relationship between MT-induced joint-related
      toxicity and anticonvulsant status was carried out. RESULTS: Forty-nine patients
      were enrolled; all were assessable for toxicity, and 46 were included in the
      efficacy analysis. Joint and muscle complaints occurred in 32 patients (65%); 1
      patient was removed from the study due to toxicity. The best protocol response
      was a complete response in 1 patient and a partial response in 2 patients
      (3/46=7%, 95% confidence interval (CI)=1, 18). Median time to progression was 24
      weeks (95% CI=16, 56), and the progression-free survival (PFS) rate was 48% at 6
      months (95% CI=35%, 65%), which surpassed the protocol objective of 40%. Sub
      analysis showed a positive impact of joint-related toxicity due to MT on PFS
      whether or not patients were taking CYP450 enzyme-inducing anticonvulsants.
      CONCLUSIONS: Even though this regimen is more efficacious than our comparator of
      historical controls in recurrent AG, the regimen was roughly equivalent to single
      agent TMZ and was associated with additional toxicity. The sub-analysis suggests
      pharmacokinetic and drug-drug interactions which may positively impact responses
      to MT.

PMID- 16639493
TI  - Cost comparison of low-field (0.23 T) MRI-guided laser ablation and surgery in
      the treatment of osteoid osteoma.
AB  - The purpose of this study was to analyze the costs of magnetic resonance imaging
      (MRI)-guided laser ablation and to compare them with the costs of surgery in the
      treatment of osteoid osteoma. Seven patients with osteoid osteoma were treated
      with MRI-guided interstitial laser ablation during 1 year. The reference material
      consisted of six patients whose osteoid osteoma was treated surgically by either
      superficial or deep excision with metallic fixation. The costs were analyzed by
      using activity-based cost accounting. The mean cost of the MRI-guided laser
      ablation was 2,392 euros and of the excision of superficially located osteoid
      osteoma 1,807 euros. The cost of excision of deeply located osteoma with metallic
      fixation was considerably higher (4,996 euros). This was due to the higher
      material, personnel, and ward costs. The cost of MRI-guided laser ablation of
      osteoid osteoma was higher than the cost of surgical excision of a superficial
      osteoma but considerably lower than the cost of excision of a deeply located
      osteoma where metallic fixation was needed. When the number and mean cost of sick
      days or days of restricted weight bearing were also included, the cost of MRI
      guided laser ablation was lower than the costs of either superficial or deep
      excision.

PMID- 16639494
TI  - Cyclic contrast-enhanced harmonic voiding urosonography for the evaluation of
      reflux. Can we keep the cost of the examination low?
AB  - The purpose of this study was to evaluate whether a second cycle of contrast
      enhanced voiding urosonography (VUS) with no added contrast medium (CM) can
      increase the detection rate of vesicoureteral reflux (VUR). One hundred twelve
      consecutive children with a mean age of 2.9 years with 224 kidney-ureter units
      (KUU) underwent two cycles of contrast-enhanced harmonic VUS. The first cycle of
      VUS was performed with 3.5-12.5 ml of suspension 300 mg/ml SH U 508 A and was
      followed immediately by a second cycle with only saline without adding CM. VUR
      was detected in 57 KUU from 44 children (39%) at the first cycle of VUS. Eight of
      the remaining 68 non-refluxing children (12%) demonstrated VUR at the second
      cycle (P=0.045). Most cases of missed reflux at the first cycle were grade II
      (75%). However, in two KUU from two children missed reflux was grade III. In one
      child reflux (grade II) was missed on the second cycle. Comparing the second
      cycle of VUS with the first cycle, concordant findings regarding the presence or
      absence as well as the grade of reflux were found in 94% of KUU. A second cycle
      of contrast-enhanced harmonic VUS with no added CM discloses significantly more
      cases of VUR at no additional cost for the examination.

PMID- 16639495
TI  - MR evaluation of pulmonary vein diameter reduction after radiofrequency catheter
      ablation of atrial fibrillation.
AB  - Fifty consecutive patients aged 52+/-12 years suffering from drug refractory
      atrial fibrillation (AF) underwent baseline and post-ablation MR angiography
      (MRA) at a mean follow-up of 4+/-3.5 months. Pulmonary vein (PV) disconnection
      was performed with a maximum energy delivery of 30 W. MRA allowed a two-plane
      measurement of each PV ostium. After ablation, no significant stenosis was
      observed, and only 1/194 (0.5%) and 3/194 (2%) PVs had a diameter reduction of 31
      40% in the coronal and axial planes, respectively. There was a significant
      overall post-procedural PV narrowing of 4.9% in the coronal plane and 6.5% in the
      axial plane (P=ns between both planes). MRA is an efficient technique that can be
      used in pre- and postoperative evaluation of AF patients. Using a maximal power
      delivery limited to 30 W, no significant PV stenosis was observed at mid-term
      follow-up. Late PV anatomical assessment is needed to confirm these results on
      long-term follow-up.

PMID- 16639496
TI  - Initial experience with magnetic resonance fluoroscopy in the evaluation of
      oesophageal motility disorders. Comparison with manometry and barium fluoroscopy.
AB  - The aim of this paper was to assess the diagnostic value of magnetic resonance
      (MR) fluoroscopy in the study of oesophageal motility disorders and to compare MR
      fluoroscopy results with those of manometry and barium contrast radiography.
      Twenty-five subjects referred for dysphagia and three patients in follow-up after
      pneumatic dilatation of the lower oesophageal sphincter to treat severe achalasia
      underwent esophageal manometry, barium contrast radiography and MR fluoroscopy.
      Examinations were performed on a 1.5 T scanner. Dynamic turbo- fast low angle
      shot (turbo-FLASH) sequences acquired during oral contrast agent administration
      were used to perform MR fluoroscopy. MR fluoroscopy correctly diagnosed achalasia
      in nine patients, uncoordination of esophageal body motility in ten and
      scleroderma oesophagus in one. Diagnostic performance was satisfactory, with a
      sensitivity of 87.5% and a specificity of 100% in the general depiction of
      motility alterations. Our work demonstrates that MR fluoroscopic examination in
      subject affected by oesophageal motility disorders is feasible and can properly
      depict motility and morphology alterations, achieving correct diagnosis in the
      majority of cases. Studies on larger populations are necessary to obtain
      statistically significant results.

PMID- 16639497
TI  - Imaging of nasopharyngeal cysts and bursae.
AB  - Cysts and bursae of the nasopharynx are uncommon and seldom symptomatic when
      compared with malignant tumors of this region. However, it is noteworthy that in
      the presence of symptoms, a good knowledge of their radiological appearance is
      useful to establish the correct diagnosis. Cysts of Rathke's pouch, pharyngeal
      bursa of Luschka, Tornwaldt's cysts, retentional cysts of the seromucinous
      glands, oncocytic cysts, intra-adenoid cysts, branchial cysts, prevertebral or
      retropharyngeal abscess and pseudocysts of the nasopharynx will be discussed in
      this paper.

PMID- 16639498
TI  - Immunoreactivities to protein gene product 9.5, neurofilament protein and neuron
      specific enolase in the ovary of the sexually immature ostrich (Struthio
      camelus).
AB  - The innervation of the ovary has been studied in various species of birds and
      mammals. Despite the fact that the innervation of any organ is an essential
      factor in controlling its growth and function, no information is available on the
      distribution of nerve fibers in the ovary of the sexually immature ostrich. Thus,
      the present study was undertaken to investigate the distribution of nerve fibers
      in the ovary of the sexually immature ostrich, using antibodies against
      neurofilament protein type M of 160 kD (NP), protein gene product 9.5 (PGP 9.5)
      and neuron specific enolase (NSE). A total of 26 sexually immature female
      ostriches, aged between 12 and 14 months were used in the present study.
      Immunostaining was performed using a LSAB plus kit (Dakocytomation, Denmark).
      Antibodies against NP and PGP 9.5 were used at dilutions of 1:25 and 1:50,
      respectively. A ready-to-use solution containing antibodies against NSE was also
      used. Strong immunostaining for NP, PGP 9.5 and NSE was observed in nerve
      bundles, which coursed through the ovarian stalk and extended into the medulla
      and cortex. In addition, NSE immunoreactive nerve cell bodies were observed in
      the cortex and medulla. NP, PGP 9.5 and NSE immunoreactive nerve fibers were
      present in the thecal layer of the follicular wall. The current study has
      highlighted the distribution of NP, PGP 9.5 and NSE-immunoreactive nerve fibers
      in the ovary of the sexually immature ostrich. The findings of the present study
      suggest that the distribution of nerve fibers in the immature ostrich is similar
      to that of the domestic fowl.

PMID- 16639499
TI  - Improving antisaccade performance in adolescents with attention
      deficit/hyperactivity disorder (ADHD).
AB  - The goal of the study was to examine the effects of task manipulations on
      antisaccade accuracy and response times (RTs) of adolescents with attention
      deficit/hyperactivity disorder (ADHD), age-matched controls, 10-year-olds and
      young adults. Order effects were tested by administering the task at the
      beginning and end of the session. Other manipulations involved a visual landmark
      to reduce demands on working memory and internal generation of saccades;
      spatially specific and non-specific cues at three intervals; and central
      engagement of attention through perceptual and cognitive means at three
      intervals. As expected, adolescents with ADHD were impaired relative to age
      matched controls in terms of accuracy and saccadic RT on the first administration
      of the task. Although their accuracy improved with most of the manipulations, it
      did not improve disproportionately compared to age-matched controls.
      Nevertheless, with most of the manipulations, they could achieve the same level
      of accuracy as unaided controls on the first administration of the task. In
      contrast, the saccadic RTs of the ADHD group came close to normal under several
      conditions, indicating that elevated antisaccade RTs in this disorder may be
      related to attentional factors. The ADHD group made more premature saccades and
      fewer corrective saccades than both the age-matched and younger groups,
      suggesting difficulties with impulsivity and goal neglect. The findings suggest
      that cognitive scaffolds can ameliorate at least some of the inhibition deficits
      in adolescents with ADHD.

PMID- 16639500
TI  - Parkinson's disease: a rethink of rodent models.
AB  - Parkinson's disease (PD) is a multifactorial disease with a complex etiology that
      results from genetic risk factors, environmental exposures and most likely a
      combination of both. Rodent models of parkinsonism aim to reproduce key
      pathogenic features of the syndrome including movement disorder induced by the
      progressive loss of dopaminergic neurons in the substantia nigra, accompanied by
      the formation of alpha-synuclein containing Lewy body inclusions. Despite the
      creation of many excellent models, both chemically induced and genetically
      engineered, there is none that accurately demonstrates these features. Recent
      pathological staging studies in man have also emphasized the significant non-CNS
      component of PD that has yet to be tackled. Herein, we summarize rodent models of
      PD and what they offer to the field, and suggest future challenges and
      opportunities.

PMID- 16639501
TI  - Afferent-mediated modulation of the soleus muscle activity during the stance
      phase of human walking.
AB  - The aim of this study was to investigate the contribution of proprioceptive
      feedback to the amplitude modulation of the soleus muscle activity during human
      walking. We have previously shown that slow-velocity, small-amplitude ankle
      dorsiflexion enhancements and reductions applied during the stance phase of the
      step cycle generate, respectively, increments and decrements on the ongoing
      soleus activity. We have also shown that the increments in soleus activity are at
      least partially mediated by feedback from group Ia fibres. In the present study,
      we further investigated the afferent-mediated contribution from muscle group II
      afferents, cutaneous and proprioceptive afferents from the foot, and load
      sensitive afferents to the soleus EMG. Slow-velocity, small-amplitude ankle
      trajectory modifications were combined with the pharmaceutical depression of
      group II polysynaptic pathways with tizanidine hydrochloride, anaesthetic
      blocking of sensory information from the foot with injections of lidocaine
      hydrochloride, and modulation of load feedback by increasing and decreasing the
      body load. The depression of the group II afferents significantly reduced the
      soleus response to the ankle trajectory modifications. Blocking sensory feedback
      from the foot did not have an effect on the soleus muscle activity. Changes in
      body load affected the ongoing soleus activity level; however, it did not affect
      the amplitude of the soleus EMG responses to the ankle trajectory modifications.
      These results suggest that the feedback from group II afferents, and possibly
      from load-sensitive afferents, contribute to the amplitude modulation of the
      soleus muscle activity during the stance phase of the step cycle. However,
      feedback from cutaneous afferents and instrinsic proprioceptive afferents from
      the foot does not seem to contribute to this muscle activation.

PMID- 16639502
TI  - The effect of trial number on the emergence of the 'broken escalator' locomotor
      aftereffect.
AB  - Walking onto a stationary platform, which had been previously experienced as
      moving generates a locomotor aftereffect (LAE), which resembles the 'broken
      escalator' phenomenon. Experimentally, this is achieved by having subjects walk
      initially onto a stationary sled (BEFORE condition), then onto a moving sled
      (MOVING condition, or adaptation trials) and then again onto the stationary sled
      (AFTER condition). Subjects are always appropriately warned of the change in
      conditions. In this paper, we ask how many adaptation trials are needed to
      produce such a LAE. Thus, in two experiments, the number of MOVING trials was
      varied between 20 and 5 (Experiment 1) and between 8 and 1 (Experiment 2). Gait
      velocity, trunk position, foot contact timing and EMG of the ankle flexor
      extensors muscles were measured. In comparison with BEFORE trials all groups in
      the AFTER trials walked inappropriately fast, experienced a large overshoot of
      the trunk and showed increased leg EMG, indicating that all groups showed a LAE.
      In each experiment, and for all variables, no significant difference between the
      groups (i.e. 20 down to one MOVING trials) was found. The study shows that this
      LAE, in contrast to other motor aftereffects reported in the literature, can be
      generated with only one or two adaptation trials and without requiring unexpected
      'catch' trials. The fast aftereffect generation observed is likely to depend on
      two types of mechanisms: (1) the nature of the sensorimotor adaptation process,
      involving multiple sensory feedbacks (visual, vestibular and proprioceptive),
      anticipatory control and large initial task errors and (2) the involvement of two
      phylogenetically old neural mechanisms, namely locomotion and fear. Fear-relevant
      mechanisms, which are notably resistant to cognitive control, may be recruited
      during the adaptation trials and contribute to the release of this LAE.

PMID- 16639503
TI  - Differential expression of two fructokinases in Oryza sativa seedlings grown
      under aerobic and anaerobic conditions.
AB  - Fructokinases (EC 2.7.1.4) may play an important role in carbohydrate metabolism
      of Oryza sativa L. (rice) seedlings under anoxia. We present here the molecular
      and biochemical characterizations of two rice fructokinases, namely OsFK1 and
      OsFK2. The results show that, at both a transcriptional and a transductional
      level, OsFK1 is preferentially expressed under aerobic conditions, whereas OsFK2
      is induced under anoxia. Substrate inhibition was demonstrated for OsFK1, while
      OsFK2 appears to be largely unaffected by fructose concentrations up to 10 mM.
      Sugar modulation of anoxia-induced proteins has been proposed, but our results on
      rice calli treated with or without glucose (10, 30 or 90 mM) for different time
      indicate that neither OsFK1 nor OsFK2 are sugar-regulated. We propose that OsFK2
      plays a major role in fructose phosphorylation under anoxic conditions.

PMID- 16639504
TI  - Humanin expression in skeletal muscles of patients with chronic progressive
      external ophthalmoplegia.
AB  - We showed that humanin (HN), an endogenous peptide against Alzheimer disease
      related insults, was expressed in muscles of patients with chronic progressive
      external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was
      recently found to block proapoptotic Bax function and exert its versatile
      cytoprotective effects in association with an increase in ATP levels, HN
      expression may thus reflect a physiological response against degenerative changes
      in the muscles of patients with CPEO. We found HN expression in all four patients
      examined, each of whom had different mitochondrial DNA mutations including two
      different single DNA deletions, multiple deletions, and no major mutations
      detected. We also found that HN expression was not linked to focal cytochrome c
      deficiency, strongly associated with the subtype of CPEO with single deletions.
      These results suggest that HN expression is more closely related to degenerative
      changes in all types of CPEO. Notably, HN was also expressed in non-degenerative
      muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G
      mutation in the mitochondrial ATPase 6 gene known to be associated with impaired
      ATP synthesis. Collectively, our findings suggest that HN may be specifically
      expressed in response to defects in energy production in muscles with
      mitochondrial abnormalities.

PMID- 16639519
TI  - Arthropathy, quality of life, depression, and anxiety in Behcet's disease:
      relationship between arthritis and these factors.
AB  - We aimed to determine arthritis frequency, quality of life (QoL), anxiety, and
      depression levels in Behcet's disease (BD) and thereby the effect of joint
      involvement on QoL, anxiety, and depression. Sixty-three patients diagnosed with
      BD according to the International Study Group Diagnostic Criteria and 45 healthy
      subjects as control were included in the study. All patients were evaluated in
      terms of clinical findings, the number and site of the joints involved,
      sacroiliac joint involvement, pain intensity, QoL, anxiety, and depression scale.
      The instruments used were Beck Depression Inventory (BDI) for depression, State
      Trait Anxiety Inventory (STAI-T) for anxiety, and Health Assessment Questionnaire
      (HAQ) and Nottingham Health Profile (NHP) for health status and QoL. Joint
      involvement was seen in 41.3% of the patients. The most characteristic form was
      asymmetric oligoarthritis, which was seen in 65.3% of the patients. The joints
      most commonly involved were found to be in the wrist (53.8%) and knee (50%).
      Sacroiliitis was found at a rate of 38.1%. In BD patients without arthritis,
      rates of men (p=0.004) and genital ulcer (p=0.001) were higher, and rates of
      erythema nodosum (p=0.001) and human leukocyte antigen B5 positivity (p=0.023)
      were less than those of BD patients with arthritis. Pain intensity (p=0.000), NHP
      (p=0.004), and HAQ (p=0.003) scores were significantly higher in BD patients with
      arthritis than those without arthritis. Pain intensity, NHP, BDI, and STAI-T
      scores were significantly higher in BD patients without arthritis than in healthy
      controls, while pain intensity, NHP, HAQ, BDI, and STAI-T scores were
      significantly higher in BD patients with arthritis than in healthy controls
      (p=0.000). In conclusion, our study establishes that arthropathy is one of the
      common manifestations of BD. Arthritis in BD affects considerably patients' pain
      levels and QoL. A multistep approach is required for these patients. We are of
      the opinion that this approach may also improve the QoL of these patients and
      prevent the activation of the disease.

PMID- 16639520
TI  - Homeless people at disadvantage in mental health services.
AB  - OBJECTIVE: The aims of this study are threefold: to depict characteristics of
      homeless at discharge from a psychiatric hospital; to describe the utilisation of
      inpatient care and treatment measures during hospitalisation; and to analyse to
      what extent psychiatric disorders and clinical variables contribute to the risk
      for homelessness at discharge. METHODS: Based on case register data we analysed
      all 28,204 people consecutively referred in 1996-2001 to psychiatric hospitals of
      a well-defined catchment area in Switzerland. RESULTS: 1% (N=269) of all
      admissions were homeless at discharge (mean age: 32.0 years; women: 27.9 %).
      Compared to other psychiatric inpatients, we found among the homeless more males,
      more people with younger age and lower education. Regarding treatment measures
      during the inpatient stay, homeless received less often psychopharmacotherapy,
      ergotherapy and physiotherapy, but more vocational training, occupational therapy
      and support by social workers. There was no difference between homeless and
      others regarding compulsory medication or seclusion. Homeless had a shorter
      length of inpatient stay. Risk factors for being homeless at discharge were:
      being homeless at admission, not living in a relationship, having a multiple
      substance abuse or a dual diagnosis, low clinical improvement during inpatient
      treatment and discharge against medical advice. DISCUSSION: To prevent
      homelessness at discharge, it is important to consider all independent
      contributors, i. e. the living situation before admission, health care
      inequalities during inpatient treatment (care received, low clinical improvement,
      discharge planning) and psychopathology.

PMID- 16639521
TI  - Recent approaches to psychological interventions for people at risk of psychosis.
AB  - With the emerging global focus on early psychosis, indicated prevention in
      schizophrenia has increasingly become a focus of psychiatric research interests.
      It has been argued that CBT may have some advantages compared with antipsychotics
      regarding this issue. According to MEDLINE, EMBASE and Psycinfo two completed
      randomised controlled trials (RCTs; PACE, Melbourne, Australia; EDIE, Manchester,
      United Kingdom) and one ongoing RCT with only preliminary results published so
      far (FETZ, Cologne/Bonn, Germany) on indicated prevention in schizophrenia
      including manualised and standardised psychological treatment can be identified.
      The aims of the present paper are to present and discuss the three approaches
      with regard to (I) inclusion, exclusion and exit criteria, (II) characteristics
      of interventions and (III) evaluations. All interventions use intake, exclusion
      and exit criteria, which have been evaluated in prospective follow-along studies.
      The approaches are based on the general structure and principles of cognitive
      behavioural therapy which have been developed, applied and evaluated in a wide
      range of mental health problems. Despite several methodological limitations, the
      first evaluations indicate some effects with regard to three possible aims of
      early intervention: (1) improvement of present possible pre-psychotic symptoms,
      (2) prevention of social decline/stagnation and (3) prevention or delay of
      progression to psychosis. Even though the first results are promising, we
      conclude that several ethical issues have to be taken into consideration and
      further predictive and therapeutic research is needed to judge whether
      psychological intervention is a realistic option for the treatment of people at
      risk of psychosis.

PMID- 16639532
TI  - Discrimination in autism within different sensory modalities.
AB  - Recent studies have suggested that unusual visual processing in autism might stem
      from enhanced visual discrimination. Although there are also many anecdotal
      reports of auditory and tactile processing disturbances in autism these have
      received comparatively little attention. It is possible that the enhanced
      discrimination ability in vision in autism might extend to other modalities and
      further that they may underlie many reports of unusual touch and audition. The
      present study investigated the performance of children with and without autism on
      auditory and tactile discrimination tasks and revealed superior auditory but
      comparable tactile discrimination in autism relative to controls. These results
      extend previous findings of perceptual discrimination in autism and may be
      relevant for a neuro-developmental hypothesis of the disorder.

PMID- 16639533
TI  - Decoding of emotion through facial expression, prosody and verbal content in
      children and adolescents with Asperger's syndrome.
AB  - This study examined differences in the ability to decode emotion through facial
      expression, prosody, and verbal content between 14 children with Asperger's
      Syndrome (AS) and 16 typically developing peers. The ability to decode emotion
      was measured by the Perception of Emotion Test (POET), which portrayed the
      emotions of happy, angry, sad, and neutral among the modalities of static and
      dynamic facial expression, prosody, verbal content, and all modalities combined.
      Results revealed that children with AS had more difficulty identifying emotions
      through static facial expression, dynamic facial expression, and prosody than
      typically developing children. Results are discussed in relationship to an over
      reliance on verbal content as a compensatory strategy in social interactions.
      Treatment implications for individuals with AS are also discussed.

PMID- 16639535
TI  - Age and sexual recidivism: a variable connection.
AB  - Meta-analysis (R. K. Hanson & M. T. Bussiere, 1998) has indicated an overall
      negative correlation between age and sexual recidivism, but also found that the
      size of this inverse relationship varies significantly between samples. The
      present study examined the relationship between age on release and sexual
      recidivism in a large (N=752), nationally representative, sample of imprisoned
      male sexual offenders followed up for 10 years. Sexual offenders released at a
      younger age tended to be more general criminals while those released at an older
      age tended to be sexual specialists. Consistent with C. F. Roberts, D. M. Doren,
      and D. Thornton (2002), age on release was found to make a significant
      contribution to the prediction of sexual reconviction when two aspects of
      criminal history (sexual deviance and general criminality) were controlled.
      Overall, the odds of being sexually reconvicted declined by about 0.02 with each
      year of increasing age. In addition to this general decline in recidivism with
      increasing age, there was also a cubic effect of age for the offenders who had
      been sentenced for sexual offenses on at least two prior occasions. This group
      showed an exceptionally high sexual recidivism rate when released between the
      ages of 18-24 (80%). For those aged between 25 and 59 their sexual reconviction
      rate was consistently just under 50% regardless of age. Then for the small group
      aged 60+ no further sexual reconvictions were found.

PMID- 16639536
TI  - Another look at interpreting risk categories.
AB  - Several studies over the past decade have shown that simple rating scales can
      accurately rank sex offenders' long-term risk of recidivism. But when using these
      scales as prediction tools, evaluators often wish to translate categories of risk
      into probabilities of recidivism. D. M. Doren (2004) has recently suggested that
      evaluators may use the recidivism percentages published in original studies of
      the RRASOR and STATIC-99 without regard to differences in populations or base
      rates. This article explains why Doren's computations should lead to a different
      conclusion, and describes how simply comparing percentages across studies can
      mislead researchers and clinicians. Instead, investigators should isolate and
      examine the detection properties of risk assessment instruments alone,
      independent of the population- or setting-specific base rate. This article
      explains this process, using an imaginary study to illustrate how base rates and
      the properties of risk assessment instruments yield estimated probabilities of
      recidivism. The article also shows why Doren's results imply that the percentages
      of recidivism associated with scores on the RRASOR and STATIC-99 scores may vary
      across study populations. The article offers recommendations for researchers who
      design and evaluate actuarial methods of assessing risk and for clinicians who
      interpret results from risk assessment instruments.

PMID- 16639541
TI  - I can use a condom, i just don't: the importance of motivation to prevent HIV in
      adolescent seeking psychiatric care.
AB  - Youth continue to show high HIV infection rates, and adolescents with mental
      health problems are especially at risk. We used longitudinal data to test a
      cognitive-behavioral model of risky sexual behavior among 175, ethnically diverse
      urban adolescents seeking mental health services. Path analyses of the cross
      sectional data revealed that Motivation was a strong predictor of Behavioral
      Skills and Sexual Risk Taking. The model explained 42% of the variance in Sexual
      Risk Taking with age included-29% without age. In the longitudinal path analyses,
      Motivation had a significant negative effect on levels of Sexual Risk Taking 6
      months later, controlling for Information, Behavioral Skills, age, and baseline
      levels of Sexual Risk Taking. These longitudinal effects explained 60% of the
      variance in Sexual Risk Taking. These results underscore the need to address
      motivational factors in HIV prevention programs designed for adolescents with
      mental health problems.

PMID- 16639542
TI  - Providers' HIV prevention discussions with HIV-seropositive injection drug users.
AB  - Public health agencies have recommended incorporating HIV prevention counseling
      into the medical care of persons living with HIV/AIDS. Injection drug users
      (IDUs) especially need HIV risk-reduction counseling because of their high risk
      for HIV transmission through both sexual and injection behaviors. The objective
      of this study was to assess the prevalence of, and patient factors associated
      with, the delivery of HIV prevention messages to HIV-seropositive IDUs in primary
      care settings. A majority of participants reported having an HIV prevention
      discussion with their provider during their most recent primary care visit.
      Factors significantly associated with report of such discussion were being
      Hispanic or non-Hispanic Black; high school education or less; and better
      perception of engagement with provider. Medical providers should provide
      prevention messages to all HIV-seropositive IDUs, regardless of demographic
      factors. Effective HIV prevention interventions in primary care settings,
      including interventions to improve patient-provider communication, are needed for
      HIV-seropositive IDUs.

PMID- 16639543
TI  - Towards a definition of orphaned and vulnerable children.
AB  - The HIV epidemic presents challenges including orphans and a large mass of
      children rendered vulnerable by the epidemic and other societal forces. Focus on
      orphaned and vulnerable children (OVC) is important, but needs accurate
      definition. Twelve focus group interviews of service providers, leaders in these
      communities, OVC and their caretakers were conducted at six project sites across
      Botswana, South Africa and Zimbabwe to extend this definition. The loss of a
      parent through death or desertion is an important aspect of vulnerability.
      Additional factors leading to vulnerability included severe chronic illness of a
      parent or caregiver, poverty, hunger, lack of access to services, inadequate
      clothing or shelter, overcrowding, deficient caretakers, and factors specific to
      the child, including disability, direct experience of physical or sexual
      violence, or severe chronic illness. Important questions raised in this research
      include the long-term implications for the child and community, and the
      contribution of culture systems.

PMID- 16639550
TI  - Vesicular release of ATP at central synapses.
AB  - Adenosine triphosphate (ATP) acts as a fast excitatory transmitter in several
      regions of the central nervous system (CNS) including the medial habenula, dorsal
      horn, locus coeruleus, hippocampus, and somatosensory cortex. Postsynaptic
      actions of ATP are mediated through an extended family of P2X receptors, widely
      expressed throughout the CNS. ATP is released via several pathways, including
      exocytosis from presynaptic terminals and diffusion through large transmembrane
      pores (e.g., hemichannels, P2X(7) receptors, or volume-sensitive chloride
      channels) expressed in astroglial membranes. In presynaptic terminals, ATP is
      accumulated and stored in the synaptic vesicles. In different presynaptic
      terminals, these vesicles may contain ATP only or ATP and another
      neurotransmitter [e.g., gamma-amino-butyric acid (GABA) or glutamate]; in the
      latter case, two transmitters can be coreleased. Here, we discuss the mechanisms
      of vesicular release of ATP in the CNS and present our own data, which indicate
      that in central neuronal terminals, ATP is primarily stored and released from
      distinct pool of vesicles; the release of ATP is not synchronized either with
      GABA or with glutamate.

PMID- 16639549
TI  - Nucleotide signaling in nervous system development.
AB  - The development of the nervous system requires complex series of cellular
      programming and intercellular communication events that lead from the early
      neural induction to the formation of a highly structured central and peripheral
      nervous system. Neurogenesis continuously takes place also in select regions of
      the adult mammalian brain. During the past years, a multiplicity of cellular
      control mechanisms has been identified, ranging from differential transcriptional
      mediators to inducers or inhibitors of cell specification or neurite outgrowth.
      While the identification of transcription factors typical for the stage-specific
      progression has been a topic of key interest for many years, less is known
      concerning the potential multiplicity of relevant intercellular signaling
      pathways and the fine tuning of epigenetic gene regulation. Nucleotide receptors
      can induce a multiplicity of cellular signaling pathways and are involved in
      multiple molecular interactions, thus opening the possibility of cross talk
      between several signaling pathways, including growth factors, cytokines, and
      extracellular matrix components. An increasing number of studies provides
      evidence for a role of nucleotide signaling in nervous system development. This
      includes progenitor cell proliferation, cell migration, neuronal and glial
      cellular interaction and differentiation, and synaptic network formation.

PMID- 16639551
TI  - Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric
      hypoxia.
AB  - Right ventricular hypertrophy induced by chronic hypoxia is mainly due to a
      mechanical stress upon the ventricular wall secondary to pulmonary arterial
      hypertension. However, the hypoxic chronic activation of the sympathetic nervous
      system can contribute to the development of right ventricular hypertrophy either
      via myocardial adrenergic receptors and/or a vasoconstriction and remodeling of
      pulmonary arteries. To highlight the specific role of the sympathetic nervous
      system on hypoxia-induced right ventricular hypertrophy and particularly the
      efficiency of carvedilol, our study compared physiological, myocardial, and
      pulmonary arterial morphometric data in rats treated by alpha-(prazosin), or beta
      (propranolol) or alphabeta-(carvedilol) antagonist and exposed to chronic
      hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia,
      both systolic right ventricular pressure and Fulton's ratio (right/(left+septum)
      ventricular weight) were lower in rats treated by prazosin (-16.7 and -13.6%),
      propranolol (-28.6 and -12.7%) and carvedilol (-15.9 and -14.3%) respectively
      when compared to glucose (p<0.05). Surprisingly, prazosin was unable to reduce
      right ventricular hypertrophy induced by chronic hypoxia, whereas, left
      ventricular weight increased. Wall thickness index of pulmonary arteries
      increased in chronic hypoxia and was reduced by carvedilol. In conclusion, the
      hypoxia-induced activation of the adrenergic system participates in the
      development of right ventricular hypertrophy. Carvedilol is effective in reducing
      hypoxia-induced right ventricular hypertrophy, pulmonary arterial hypertension,
      and muscularization of pulmonary arteries.

PMID- 16639557
TI  - New concepts in chemical and biological monitoring of priority and emerging
      pollutants in water.

PMID- 16639553
TI  - Exploring concerns of children with cancer.
AB  - BACKGROUND: Aggressive treatment protocols in pediatric oncology have major
      effects on the lives of children with cancer. The effects of lifestyle changes
      such as hospitalization and home schooling on quality of life have not been
      investigated. This study explores lifestyle effects of cancer therapy on the
      quality of life of children with cancer. The goals of this study were to identify
      important quality-of-life issues from the perspectives of children with cancer
      and to identify how they think their experience with cancer treatment could be
      improved. MATERIALS AND METHODS: Pediatric oncology patients age 5-21 were
      interviewed individually. Sample questions included, "Ever since you got sick,
      what has bothered you the most?" and "How has having this illness affected your
      life?" Responses were analyzed using standard qualitative techniques. RESULTS:
      Thirty-one patients were interviewed in depth. Four major themes emerged
      including (1) loneliness and isolation: the loss of a normal childhood, (2)
      decreased pleasure from food, (3) physical discomfort and disability, and (4)
      emotional responses to cancer, specifically anger and fear. Their suggestions for
      improvement included better-tasting food, more comfortable hospital decor, and
      social activities with children their own age. CONCLUSIONS: Children cited
      concerns regarding pleasures taken away as well as pain inflicted due to cancer
      treatment. In addition to traditionally mentioned side effects, children
      complained of difficulty enjoying food and restricted social activity. To improve
      the quality of life of children with cancer, healthcare providers should focus on
      potentially modifiable variables including food-related pleasure, hospital
      aesthetics, and social activity.

PMID- 16639559
TI  - Genetically modified crops: success, safety assessment, and public concern.
AB  - With the emergence of transgenic technologies, new ways to improve the agronomic
      performance of crops for food, feed, and processing applications have been
      devised. In addition, ability to express foreign genes using transgenic
      technologies has opened up options for producing large quantities of commercially
      important industrial or pharmaceutical products in plants. Despite this high
      adoption rate and future promises, there is a multitude of concerns about the
      impact of genetically modified (GM) crops on the environment. Potential
      contamination of the environment and food chains has prompted detailed
      consideration of how such crops and the molecules that they produce can be
      effectively isolated and contained. One of the reasonable steps after creating a
      transgenic plant is to evaluate its potential benefits and risks to the
      environment and these should be compared to those generated by traditional
      agricultural practices. The precautionary approach in risk management of GM
      plants may make it necessary to monitor significant wild and weed populations
      that might be affected by transgene escape. Effective risk assessment and
      monitoring mechanisms are the basic prerequisites of any legal framework to
      adequately address the risks and watch out for new risks. Several agencies in
      different countries monitor the release of GM organisms or frame guidelines for
      the appropriate application of recombinant organisms in agro-industries so as to
      assure the safe use of recombinant organisms and to achieve sound overall
      development. We feel that it is important to establish an internationally
      harmonized framework for the safe handling of recombinant DNA organisms within a
      few years.

PMID- 16639560
TI  - Novel blastospore-based transformation system for integration of phosphinothricin
      resistance and green fluorescence protein genes into Beauveria bassiana.
AB  - A novel system was developed for efficient transformation of the fungal
      biocontrol agent Beauveria bassiana. Competent blastospores were prepared and
      stored in LiAc- and glycerol-inclusive suspension at -76 degrees C for sequential
      use in transformation. The system was successfully applied to integrating
      phosphinothricin resistance gene bar and enhanced green fluorescence protein gene
      egfp into B. bassiana via blastospore absorption of a plasmid vectoring bar and
      egfp. A frequency of 24 transformants per microgram of DNA was achieved. The
      blastospore-based transformation system has proven to be very convenient and
      would be highly potential for use in genetic manipulation of B. bassiana and
      other filamentous species.

PMID- 16639561
TI  - Synchronous colorectal adenocarcinoma and gastrointestinal stromal tumor (GIST).
AB  - BACKGROUND: Little is known about the synchronous occurrence of gastrointestinal
      stromal tumors (GISTs) and other gastrointestinal tumors. We present two cases of
      an invasive colon cancer with a synchronous small-bowel GIST;
      immunohistochemistry studies were performed to evaluate possible genetic
      similarities. METHODS: This paper reports two cases of synchronous GISTs and
      colorectal cancer (CRC) with immunohistochemistry analysis of c-Kit expression.
      This paper is also a review of the existing literature on the association of
      GISTs and CRC and the role of c-Kit in CRC. RESULTS: In the last 2 years, we
      observed two patients with synchronous CRCs and GISTs of the small bowel. The
      GISTs were incidentally discovered during the work-up for CRCs and excised at the
      time of the colon resection. Immunohistochemistry study did not reveal an
      expression of c-Kit in CRCs. Clinical implications of the association between
      these two neoplasms are described in this paper. CONCLUSIONS: Synchronous CRC and
      GIST has been more frequently reported. Because of the limited number of cases,
      we cannot exclude an incidental relationship. The genetic pathways of
      tumorigenesis appear different for the two neoplasms. Further studies are needed
      to clarify a possible role of c-Kit in the development of colonic
      adenocarcinomas.

PMID- 16639562
TI  - Endovascular management of dural carotid-cavernous sinus fistulas in 141
      patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate the single-centre
      experience with transvenous coil treatment of dural carotid-cavernous sinus
      fistulas. METHODS: Between November 1991 and December 2005, a total of 141
      patients (112 female) with dural carotid-cavernous sinus fistula underwent 161
      transvenous treatment sessions. The patient files and angiograms were analysed
      retrospectively. Clinical signs and symptoms included chemosis (94%),
      exophthalmos (87%), cranial nerve palsy (54%), increased intraocular pressure
      (60%), diplopia (51%), and impaired vision (28%). Angiography revealed in
      addition cortical drainage in 34% of the patients. Partial arterial embolization
      was carried out in 23% of the patients. Transvenous treatment comprised in by far
      the majority of patients complete filling of the cavernous sinus and the adjacent
      segment of the superior and inferior ophthalmic vein with detachable coils.
      RESULTS: Complete interruption of the arteriovenous shunt was achieved in 81% of
      the patients. A minor residual shunt (without cortical or ocular drainage)
      remained in 13%, a significant residual shunt (with cortical or ocular drainage)
      remained in 4%, and the attempted treatment failed in 2%. There was a tendency
      for ocular pressure-related symptoms to resolve rapidly, while cranial nerve
      palsy and diplopia improved slowly (65%) or did not change (11%). The 39 patients
      with visual impairment recovered within the first 2 weeks after endovascular
      treatment. After complete interruption of the arteriovenous shunt, no recurrence
      was observed. CONCLUSION: The transvenous coil occlusion of the superior and
      inferior ophthalmic veins and the cavernous sinus of the symptomatic eye is a
      highly efficient and safe treatment in dural carotid-cavernous sinus fistulas. In
      the majority of patients a significant and permanent improvement in clinical
      signs and symptoms can be achieved.

PMID- 16639564
TI  - The effects of resource enrichment, dispersal, and predation on local and
      metacommunity structure.
AB  - Community structure is the observable outcome of numerous processes. We conducted
      a laboratory experiment using a microbial model system to disentangle effects of
      nutrient enrichment, dispersal, and predation on prey species richness and
      predator abundance at local and metacommunity scales. Prey species included:
      Chilomonas sp., Colpidium striatum, Colpoda cucullus, Paramecium tetraurelia, P.
      caudatum, Philodina sp., Spirostomum sp., Tetrahymena thermophila, and Uronema
      sp., and Stentor coeruleus was the predator used. We hypothesized that: (1)
      increased basal resources should maintain greater species richness and higher
      predator abundance; (2) dispersal should maintain greater species richness; and
      (3) predation should reduce species richness, especially in the high resource
      treatments relative to no-predator treatments. Our results support all three
      hypotheses. Further, we show that dispersal affects richness at the local
      community scale but not at the metacommunity scale. However, predation seems to
      have major effects at both the local and metacommunity scale. Overall, our
      results show that effects of resource enrichment, dispersal, and predation were
      mostly additive rather than interactive, indicating that it may be sometimes
      easier to understand their effects than generally thought due to complex
      interactive effects.

PMID- 16639565
TI  - Stoichiometry and large-scale patterns of leaf carbon and nitrogen in the
      grassland biomes of China.
AB  - Nitrogen (N) and carbon-nitrogen (C:N) ratio are key foliar traits with great
      ecological importance, but their patterns across biomes have only recently been
      explored. We conducted a systematic census of foliar C, N and C:N ratio for 213
      species, from 41 families over 199 research sites across the grassland biomes of
      China following the same protocol, to explore how different environmental
      conditions and species composition affect leaf N and C:N stoichiometry. Leaf C:N
      stoichiometry is stable in three distinct climatic regions in Inner Mongolia, the
      Tibetan Plateau, and Xinjiang Autonomous Region, despite considerable variations
      among co-existing species and among different vegetation types. Our results also
      show that life form and genus identity explain more than 70% of total variations
      of foliar N and C:N ratio, while mean growing season temperature and growing
      season precipitation explained only less than 3%. This suggests that, at the
      biome scale, temperature affects leaf N mainly through a change in plant species
      composition rather than via temperature itself. When our data were pooled with a
      global dataset, the previously observed positive correlation between leaf N and
      mean annual temperature (MAT) at very low MATs, disappeared. Thus, our data do
      not support the previously proposed biogeochemical hypothesis that low
      temperature limitations on mineralization of organic matter and N availability in
      soils lead to low leaf N in cold environments.

PMID- 16639566
TI  - Brood parasitism increases provisioning rate, and reduces offspring recruitment
      and adult return rates, in a cowbird host.
AB  - Interspecific brood parasitism in birds presents a special problem for the host
      because the parasitic offspring exploit their foster parents, causing them to
      invest more energy in their current reproductive effort. Nestling brown-headed
      cowbirds (Molothrus ater) are a burden to relatively small hosts and may reduce
      fledgling quality and adult survival. We documented food-provisioning rates of
      one small host, the prothonotary warbler (Protonotaria citrea), at broods that
      were similar in age (containing nestlings 8-9 days old), but that varied in
      composition (number of warbler and cowbird nestlings) and mass, and measured the
      effect of brood parasitism on offspring recruitment and adult returns in the
      host. The rate of food provisioning increased with brood mass, and males and
      females contributed equally to feeding nestlings. Controlling for brood mass, the
      provisioning rate was higher for nests with cowbirds than those without.
      Recruitment of warbler fledglings from unparasitized nests was 1.6 and 3.7 times
      higher than that of fledglings from nests containing one or two cowbirds,
      respectively. Returns of double-brooded adult male and female warblers decreased
      with an increase in the number of cowbirds raised, but the decrease was more
      pronounced in males. Reduced returns of warbler adults and recruitment of warbler
      fledglings with increased cowbird parasitism was likely a result of reduced
      survival. Cowbird parasitism increased the warblers' investment in current
      reproductive effort, while exerting additional costs to current reproduction and
      residual reproductive value. Our study provides the strongest evidence to date
      for negative effects of cowbird parasitism on recruitment of host fledglings and
      survival of host adults.

PMID- 16639567
TI  - Solar ultraviolet-B radiation alters the attractiveness of Arabidopsis plants to
      diamondback moths (Plutella xylostella L.): impacts on oviposition and
      involvement of the jasmonic acid pathway.
AB  - Solar ultraviolet-B radiation (UV-B) can have large impacts on the interactions
      between plants and herbivorous insects. Several studies have documented effects
      of UV-B-induced changes in plant tissue quality on the feeding performance of
      insect larvae. In contrast, the effects of UV-B-induced plant responses on the
      behavior of adult insects have received little attention. We carried out a series
      of field and glasshouse experiments using the model plant Arabidopsis thaliana L.
      and the crucifer-specialist insect Plutella xylostella L. (diamondback moth) to
      investigate the effects of UV-B on natural herbivory and plant-insect
      interactions. Natural herbivory under field conditions was less severe on plants
      exposed to ambient UV-B than on plants grown under filters that attenuated the UV
      B component of solar radiation. This reduced herbivory could not be accounted for
      by effects of UV-B on larval feeding preference and performance, as P. xylostella
      caterpillars did not respond to changes in plant quality induced by UV-B. In
      contrast, at the adult stage, the insects presented clear behavioral responses:
      P. xylostella moths deposited significantly more eggs on plants grown under
      attenuated UV-B levels than on plants exposed to ambient UV-B. The deterring
      effect of UV-B exposure on insect oviposition was absent in jar1-1, a mutant with
      impaired jasmonic acid (JA) sensitivity, but it was conserved in mutants with
      altered ethylene signaling. The jar1-1 mutant also presented reduced levels of UV
      absorbing phenolic compounds than the other genotypes that we tested. Our results
      suggest that variations in UV-B exposure under natural conditions can have
      significant effects on insect herbivory by altering plant traits that female
      adults use as sources of information during the process of host selection for
      oviposition. These effects of natural UV-B on plant quality appear to be mediated
      by activation of signaling circuits in which the defense-related hormone JA plays
      a functional role.

PMID- 16639568
TI  - Hydraulic compensation in northern Rocky Mountain conifers: does successional
      position and life history matter?
AB  - As trees grow tall and the resistance of the hydraulic pathway increases, water
      supply to foliage may decrease forcing stomata to close and CO2 uptake to
      decline. Several structural (e.g. biomass allocation) and physiological
      adjustments, however, may partially or fully compensate for such hydraulic
      constraints and prevent limitations on CO2 uptake and growth. The degree to which
      trees compensate for hydraulic constraints as they grow tall may depend on the
      costs and benefits associated with hydraulic compensation according to their
      ecology and life history. Because later successional Rocky Mountain conifers are
      more shade tolerant, optimization of CO2 uptake as trees grow tall and shade
      increases may confer greater benefits than in earlier successional species. If
      so, higher compensation for hydraulic constraints is expected in later
      successional species relative to co-occurring earlier successional species. I
      have examined height-related changes of crown stomatal conductance on a leaf area
      basis (G(LA)) and leaf to sapwood ratios (A(L):A(S)) for five conifer species in
      the northern Rocky Mountains. Species were arranged in pairs, each pair
      consisting of an early and late successional species. For high elevations I used,
      respectively, whitebark pine (Pinus albicaulis) and subalpine fir (Abies
      lasiocarpa); for mid-elevations, western larch (Larix occidentalis) and Douglas
      fir (Pseudotsuga menziesii); for lower elevations, ponderosa pine (Pinus
      ponderosa) and Douglas-fir. A(L):A(S) either decreased (subalpine fir, ponderosa
      pine), remained constant (Douglas-fir, western larch) or increased (whitebark
      pine) with tree height. As hypothesized, earlier successional species (ponderosa
      pine, whitebark pine and western larch) exhibited significantly stronger
      decreases of G(LA) with tree height relative to their later successional pairs
      (Douglas-fir and subalpine fir), which fully compensated for height-related
      hydraulic constraints on G(LA). A life history approach that takes into account
      the optimization of size- and species-specific ecological functions may also help
      researchers better understand biomass allocation and hydraulic function in trees.

PMID- 16639569
TI  - Food supply controls the body condition of a migrant bird wintering in the
      tropics.
AB  - The hypothesis that migratory bird populations are limited during the non
      breeding season is increasingly supported by empirical studies that also suggest
      consequences that carry-over into subsequent seasons. Although variation in food
      supply is the best supported explanation for non-breeding season limitation, the
      ecological mechanisms and physiological consequences are not well understood. We
      both supplemented and reduced Ovenbird (Seiurus aurocapilla) food availability on
      replicate plots in Jamaica in each of 3 years to determine the direct role of
      food in limiting the physical condition of Ovenbirds. Annual variation in
      rainfall and food supply created a natural experiment in parallel with
      manipulations. Sex and age-classes of Ovenbirds did not respond differently in
      terms of body condition to either food manipulation or natural variation in
      environmental conditions, suggesting that this population is not structured by
      strong dominance relationships. Ovenbird body mass, fat, and pectoralis muscle
      shape were positively and predictably related to manipulated food availability.
      Feather regrowth rate also responded positively to food supplementation and
      negatively to food reduction in the drier of 2 years. Prior to manipulation,
      annual variation in body mass corresponded to annual variation in food supply and
      rainfall, providing additional, correlational evidence of food limitation. Since
      multiple intercorrelated body condition indices of Ovenbirds responded directly
      to food supply, and since food supply influenced body condition independently of
      other habitat features, we argue that food is a primary driver of non-breeding
      season population limitation. Moreover, since these effects were observed during
      the late non-breeding period, when individuals are preparing to migrate, we infer
      that food availability likely initiates carry-over effects.

PMID- 16639570
TI  - Disturbance, biological legacies and community development in stream mesocosms.
AB  - Disturbances reduce the biota in stream ecosystems, and leave biological
      legacies, including remnant species, which potentially influence post-disturbance
      community development but are poorly understood. We investigated whether three
      remnant species, the snail Radix peregra, the mayfly Serratella ignita and the
      freshwater shrimp Gammarus pulex, affected community development in mesocosms
      that mimicked disturbed habitat patches in streams. Following 21 days of
      colonisation, we found that the occurrence of legacy effects depended on the
      identity of the remnant species. Radix had the strongest effect. By bulldozing
      epilithon, the snails acted as ecological engineers that promoted settlement of
      filter feeders (Simuliidae) and invertebrate predators (especially Pentaneura and
      Aphelocheirus) and strongly deterred settlement of non-predatory chironomids
      (e.g. Heterotrissocladius and Microtendipes). Gammarus increased in density (by
      665%) where remnant, probably through rapid reproduction. Baetis and Pentaneura
      were scarce, and Asellus absent, in remnant Gammarus treatments, as a consequence
      of interference and/or predation by the amphipods. In contrast, Serratella
      tolerated the colonisation of immigrant species and did not affect the structure
      of the developing benthic community. Despite the observed effects on the presence
      and abundance of benthos, remnant fauna had no significant effect on assemblage
      taxon richness, or that of any specific trophic group. The contrasting effects of
      remnant species on immigrant colonisation echoed differences in their life
      history traits and foraging behaviours. Our results indicate that biota can
      generate spatial patchiness of epilithon and benthic invertebrates in stream
      ecosystems.

PMID- 16639571
TI  - Rituximab long-term maintenance therapy after autologous stem cell
      transplantation in patients with B-cell non-Hodgkin's lymphoma.
AB  - Treatment of B-cell non-Hodgkin's lymphomas (NHL) with either Rituximab alone or
      in combination with cytotoxic chemotherapy has been effective without major side
      effects. Thus, Rituximab maintenance therapy after autologous peripheral blood
      stem cell transplantation (PBSCT) might represent an improvement in NHL therapy.
      We therefore retrospectively analyzed the efficacy and side effects of monthly
      long-term Rituximab maintenance therapy after PBSCT in 27 patients with NHL. In
      median 10 infusions of Rituximab were given after PBSCT in time intervals of 1
      month. Molecular monitoring of t(14;18) was performed using nested as well as
      quantitative real time polymerase chain reaction (RT-PCR) based on the
      LightCycler technology. Side effects according to common toxicity criteria (CTC)
      > II did mainly affect the hematopoietic system. In total, 10 patients (37%)
      suffered form grade III-IV hematotoxicity. Except for two patients with cutaneous
      Varicella-Zoster infection no serious infectious complications (CTC grade III/IV)
      occurred. No patient died because of treatment-related causes. This adverse event
      data compared favorably to the published data. Three patients had t(14;18) nested
      RT-PCR positive results before Rituximab therapy and converted to negativity
      after Rituximab therapy. We conclude that a prolonged Rituximab maintenance
      therapy after PBSCT with monthly administration is reliable and safe.

PMID- 16639576
TI  - Viability of human-derived probiotic lactobacilli in ice cream produced with
      sucrose and aspartame.
AB  - A mixture of human-derived probiotic strains of Lactobacillus acidophilus, L.
      agilis and L. rhamnosus was used as a probiotic culture in ice cream manufacture.
      Viability and survival of these probiotic cultures were investigated in two
      different ice cream formulations. Ice cream with sucrose and ice cream with
      aspartame were prepared and each of these was divided into two subgroups: one
      with direct addition of the probiotic culture and one with milk fermented by the
      same probiotic culture. Ice cream samples were stored at -20 degrees C for 6
      months and the survival rate of cultures were determined monthly. Probiotic
      cultures underwent tests for resistance to bile salts, antibiotics, acidic
      conditions; they were found to be highly resistant to such challenges. Chemical
      analysis of ice cream samples, such as determination of acidity, pH and solid
      matter, was also performed. The probiotic cultures remained unchanged in ice
      cream stored for up to 6 months regardless of the sweeteners used. Using
      probiotic cultures in ice cream mixes did not alter the characteristics of the
      product.

PMID- 16639578
TI  - Peutz-Jeghers syndrome.

PMID- 16639582
TI  - Modeling the dynamics of sensory reweighting.
AB  - Reweighting sensory information adaptively is considered critical for flexible
      postural control, but little is known of the time scale of the reweighting
      process. We analyzed the transient dynamics of sensory reweighting in a
      previously published nonlinear adaptive model of sensory integration in the human
      postural control system. The model's dynamics of adaptation were tested in
      response to abrupt changes in the amplitude of the motion of the visual surround.
      In addition to qualitatively reproducing the correct asymptotic response to such
      changes in visual amplitude, as previously found, the model qualitatively
      reproduced the asymmetric transient response elucidated in recent experiments
      (Oie et al. in Gait Posture 2005). In particular, the model adapts at an
      initially rapid rate to a switch from low to high amplitude visual motion, but at
      an initially slower rate upon the return to low amplitude motion. The observed
      temporal asymmetry has potential functional value. Rapid downweighting of a
      visual stimulus that suddenly increases is necessary to prevent loss of upright
      equilibrium. A visual stimulus that decreases in amplitude does not pose a threat
      to upright balance, allowing for slower upweighting without functional
      consequence.

PMID- 16639583
TI  - [Stay young even when you age. An introductory statement].

PMID- 16639588
TI  - Effects of organic chemicals derived from ambient particulate matter on lung
      inflammation related to lipopolysaccharide.
AB  - The effects of components of ambient particulate matter (PM) on individuals with
      predisposing respiratory disorders are not well defined. We have previously
      demonstrated that airway exposure to diesel exhaust particles (DEP) or organic
      chemicals (OC) extracted from DEP (DEP-OC) enhances lung inflammation related to
      bacterial endotoxin (lipopolysaccharide, LPS). The present study aimed to examine
      the effects of airway exposure to OC extracted from urban PM (PM-OC) on lung
      inflammation related to LPS. ICR mice were divided into four experimental groups
      that intratracheally received vehicle, LPS (2.5 mg/kg), PM-OC (4 mg/kg), or PM-OC
      + LPS. Lung inflammation, lung water content, and lung expression of cytokines
      were evaluated 24 h after intratracheal administration. LPS challenge elicited
      lung inflammation evidenced by cellular profiles of bronchoalveolar lavage fluid
      and lung histology, which was further aggravated by the combined challenge with
      PM-OC. The combination with PM-OC and LPS did not significantly exaggerate LPS
      elicited pulmonary edema. LPS instillation induced elevated lung expression of
      interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage
      chemoattractant protein-1, and keratinocyte chemoattractant, whereas the combined
      challenge with PM-OC did not influence these levels. All the results were
      consistent with our previous reports on DEP-OC. These results suggest that the
      extracted organic chemicals from PM exacerbate infectious lung inflammation. The
      mechanisms underlying the enhancing effects are not mediated via the enhanced
      local expression of proinflammatory cytokines.

PMID- 16639589
TI  - Species difference in the induction of hepatic CYP1A subfamily enzymes,
      especially CYP1A2, by 2-methoxy-4-nitroaniline among rats, mice, and guinea pigs.
AB  - Species difference in the induction of hepatic cytochrome P450 CYP1A subfamily
      enzymes by 2-methoxy-4-nitroaniline (2-MeO-4-NA) was investigated among male F344
      rats, C57BL/6 Cr mice, and Hartley guinea pigs. All species of animals were
      treated with a single ip injection of 2-MeO-4-NA (0.44 mmol/kg body weight), and
      changes in levels of the mRNA and protein of hepatic cytochrome P4501A (CYP1A)
      subfamily enzymes were examined by the methods of RT-PCR and Western blot,
      respectively. In addition, hepatic microsomal enzyme activities were measured
      using methoxyresorufin and ethoxyresorufin as substrates of CYP1A2 and CYP1A1,
      respectively. The overall results of the RT-PCR, Western blot, and measurement of
      the enzyme activity indicated that 2-MeO-4-NA-mediated induction of hepatic CYP1A
      subfamily enzymes, especially CYP1A2, occurred only in rats but not any other
      species of animals examined and that the species difference in the CYP1A
      induction was not necessarily correlated with that in pharmacokinetics of 2-MeO-4
      NA. Furthermore, a luciferase reporter gene assay for screening of the ligands of
      arylhydrocarbon receptor (AhR) using a rat hepatic cell line suggested that 2-MeO
      4-NA is not an AhR ligand. The present findings demonstrate for the first time
      the species difference in the 2-MeO-4-NA-mediated induction of hepatic CYP1A
      subfamily enzymes between rats and other rodents, mice and guinea pigs, and
      further propose an AhR-independent pathway for 2-MeO-4-NA-mediated induction in
      rats.

PMID- 16639590
TI  - Hormonal activity of combinations of genistein, bisphenol A and 17beta-estradiol
      in the female Wistar rat.
AB  - Phytoestrogens have been described as weak estrogens, selective estrogen receptor
      mediators (SERMs) or to exhibit antiestrogenic properties. However, information
      about their activity in combination with xenoestrogens and 17beta-estradiol in
      vivo, is limited. Therefore, the combinatory activity of the phytoestrogen
      genistein (Gen), the industrial chemical bisphenol A (BPA), and ethinylestradiol
      (EE) in ovariectomized Wistar rats was analyzed in this study. All compounds were
      administered orally on three consecutive days (EE at 30 microg, Gen at 100 mg and
      BPA at 200 mg per kg body weight per day). The pure antiestrogen fulvestrant (3
      mg/kg) served as estrogen receptor (ER) antagonist control. Effects on uterine
      wet weight, height of the uterine epithelium, uterine clusterin (Clu) and
      complement C3 expression, and the height of the vaginal epithelium were examined.
      Treatment with Gen alone resulted in a moderate stimulation of uterine weight; in
      the vagina the height of the epithelium was strongly stimulated. BPA did not
      stimulate any of the above-mentioned parameters significantly. In combination
      with EE, Gen acted on most of the analyzed parameters in an additive manner,
      whereas BPA significantly antagonized the effects of EE on the uterine epithelium
      and uterine Clu expression. Given in combination with Gen, BPA was also able to
      antagonize the stimulatory effect of Gen on the uterine epithelium. In summary,
      our results demonstrate that Gen, in contrast to BPA, does not exhibit any
      antiestrogenic properties, even if given at high concentrations. The results of
      this study characterize BPA as a functional antiestrogen, very likely the result
      of a lack of ability to activate ER-mediated transactivation after binding to the
      receptor. This is not the case for Gen. Our results point to the involvement of
      complex molecular mechanisms in the action of Gen. These mechanisms, especially
      the role of ERbeta have to be characterized in further investigations.

PMID- 16639591
TI  - Genetic polymorphism of cytochrome P450s in beagles: possible influence of CYP1A2
      deficiency on toxicological evaluations.
AB  - A number of human cytochrome P450 (CYP) isozymes have been shown to be
      genetically polymorphic, and extensive pharmaceutical studies have been conducted
      to characterize the clinical relevance of the polymorphism. Although the beagle
      is extensively used in the safety assessment studies of new drug candidates and
      agricultural chemicals, only a limited number of studies have been reported on
      the significance of the CYP isozyme polymorphism in dogs. Recently, a single
      nucleotide polymorphism that results in a deficiency of canine CYP1A2 was
      discovered. This deficiency was shown to significantly alter the pharmacokinetic
      behavior of two drugs, and can be associated with a large inter-individual
      difference in the kinetic behavior of a third. In this article, the five
      genetically polymorphic canine CYP isozymes that have been reported so far are
      reviewed, and the altered pharmacokinetics of the drugs concerned are described.
      Although little information on toxicological relevance has been reported, it is
      possible that the modified pharmacokinetics may also cause altered toxic
      responses as well. This phenomenon may occur only with the types of chemicals
      that are eliminated mainly through polymorphic-enzyme mediated metabolism.
      However, it is recommended that genetically pure beagles are used for the
      toxicity studies and safety assessment of new chemical entities in order to
      reduce the potential inter-individual differences.

PMID- 16639592
TI  - Clinical profile of long-term survivors of breast or thyroid cancer with
      metastatic spinal tumours.
AB  - Patients with breast or thyroid cancer with metastatic spinal tumours are
      expected to survive relatively longer than patients with other cancers with
      metastatic spinal tumours. The purpose of this study was to determine the
      clinical characteristics of long-term survivors of breast or thyroid cancer with
      metastatic spinal tumours. We studied the clinical profile of long-term survivors
      by comparing the characteristics of nine patients who had survived for at least 5
      years after a spinal operation with the characteristics of 16 patients who had
      not. Our results showed that the longer the time from the diagnosis of the
      primary cancer to the spinal operation, the longer patients with breast or
      thyroid cancer and metastatic spinal tumours would survive. Six of the eight
      patients (75.0%) who had undergone the spinal operation at least 5 years after
      the diagnosis of the primary cancer survived especially long. In conclusion, the
      duration from the diagnosis of the primary cancer to the spinal operation is very
      useful for predicting a prognosis in patients with breast or thyroid cancer and
      metastatic spinal tumours.

PMID- 16639593
TI  - The incidence of avascular necrosis of the healthy, contralateral femoral head at
      the end of the use of Pavlik harness in unilateral hip dysplasia.
AB  - We examined the incidence of avascular necrosis (AVN) of the healthy femoral head
      in unilateral hip dysplasia at the end of the use of the Pavlik harness. The
      evaluation of AVN was done with the help of standardised roentgenograms. Between
      1974 and 1982, 1,064 dysplastic hips (869 children) were treated with the Pavlik
      harness at the Orthopaedic Department of Semmelweis University. Of these, 674
      children who had unilateral hip dysplasia were chosen for this study. In the
      period of our investigation, ultrasonography was not yet used routinely, so in
      some cases the hip was mistakenly diagnosed as dysplastic. The average patient
      age was 3.2 months, and the average length of treatment was 4.9 months. We found
      no correlation between the appearance of AVN in the healthy hips at the end of
      treatment with the Pavlik harness and the age of the child at the start of
      treatment. On the other hand, there was a strong significant correlation between
      the appearance of AVN and the length of treatment.

PMID- 16639594
TI  - Cement pressurisation in the acetabulum.
AB  - Cement pressurisation is an important step in total hip arthroplasty that
      determines the long-term integration at the cement-bone interface. Our aim was to
      evaluate the performance of a new pressuriser designed by us against the standard
      existing pressurisers in an in vitro experimental set-up using two parameters:
      cement penetration and cement pressurisation. A polypropylene cup model was
      designed to represent the acetabulum. DePuy's T-handle, Exeter and our own
      plunger type pressuriser were each tested for cement pressurisation in this
      acetabular model. Cement penetration and pressures were measured. The cement
      intrusion into the capillaries with the DePuy pressuriser was found to vary
      between 2 and 8 mm (mean: 5 mm at the pole and 4.6 mm at the rim), with the
      Exeter pressuriser it varied between 3 and 9 mm (mean: 5.8 mm at the pole and 7.8
      mm at the rim) and with the plunger type pressuriser it varied between 4 and 6 mm
      (mean 5.2 mm at the pole and 4.8 mm at the rim). The peak pressure achieved with
      the DePuy pressuriser was 60 kPa whereas it was 70 kPa with the plunger type
      pressuriser. The mean penetration with the plunger type pressuriser was found to
      be better than the other types. The penetration was found to be more uniform with
      equal penetration at the rim as well as at the pole.

PMID- 16639599
TI  - Numbats and aardwolves--how low is low? A re-affirmation of the need for
      statistical rigour in evaluating regression predictions.
AB  - Many comparative physiological studies aim to determine if a particular species
      differs from a prediction based on a linear allometric regression for other
      species. However, the judgment as to whether the species in question conforms to
      this allometric relationship is often not based on any formal statistical
      analysis. An appropriate statistical method is to compare the new species' value
      with the 95% confidence limits for predicting an additional datum from the
      relationship for the other species. We examine the basal metabolic rate (BMR) of
      the termitivorous numbat (Myrmecobius fasciatus) and aardwolf (Proteles
      cristatus) to demonstrate the use of the 95% prediction limits to determine
      statistically if they have a lower-than-expected BMR compared to related species.
      The numbat's BMR was 83.6% of expected from mass, but fell inside the 95%
      prediction limits for a further datum; a BMR < 72.5% of predicted was required to
      fall below the one-tail 95% prediction limits. The aardwolf had a BMR that was
      only 74.2% of predicted from the allometric equation, but it also fell well
      within the 95% prediction limits; a BMR of only 41.8% of predicted was necessary
      to fall below the one-tail 95% prediction limits. We conclude that a formal
      statistical approach is essential, although it is difficult to demonstrate that a
      single species statistically differs from a regression relationship for other
      species.

PMID- 16639605
TI  - Intraductal papillary mucinous neoplasm (IPMN) of the gastric-type with focal
      nodular growth of the arborizing papillae: a case of high-grade transformation of
      the gastric-type IPMN.
AB  - We present a case of intraductal papillary mucinous neoplasm (IPMN) of the
      pancreas, demonstrating a process of high-grade transformation of the gastric
      type IPMN. An 83-year-old Japanese woman underwent pylorus-preserving
      pancreatoduodenectomy for removal of a multicystic mass of the pancreas head,
      which had been followed up for 7 years. The removed tumor was a low-grade gastric
      type IPMN spreading in the branch ducts, focally forming an intraluminal nodular
      lesion. The nodular lesion was comprised of arborizing papillotubular
      proliferation of cuboidal to columnar epithelia with high-grade atypia, and was
      characterized by diffuse MUC1 expression and a gastric mucin phenotype (focal
      MUC5AC and MUC6 expressions). Therefore, the nodular lesion was consistent with
      the pancreatobiliary-type IPMN, and the present case suggests that the low-grade
      gastric-type IPMN may progress to a focal intraductal carcinoma over the years,
      and the pancreatobiliary-type IPMN may be one of the forms of such high-grade
      transformation of the gastric-type IPMN. One of the cystic lesions was an
      oligocystic-type serous cystic neoplasm (serous cystadenoma), which might be an
      incidental concomitance or have a common basis.

PMID- 16639606
TI  - Lung osteoma--a new benign lung lesion.
AB  - Extraskeletal osteomas have not been described in the lung. Tumors with osseous
      elements can be found, such as hamartoma and amyloid tumor, and reactive lesions
      such as osseous metaplasia. A 39-year-old male patient was treated for multiple
      myeloma and got a bone marrow transplantation 2 years and a few months before he
      presented with a solitary well-circumscribed tumor in the right middle lobe. The
      patient underwent surgical resection. The tumor presented with a fibrous capsule
      and consisted of mature bone trabecules. Within the tumor, fatty tissue was seen.
      There were small bone spicules interpreted as areas of new bone formation and
      appositional growth. No amyloid deposition, no immature epithelial tubules as in
      hamartomas, and no normal lung structure as in osseous metaplasia were seen.
      Within the osseous elements, a positive reaction was seen with antibodies for
      osteonectin, whereas the reaction for calcitonin was negative. To the best of our
      knowledge, this is the first case of an osteoma being reported in the lung
      looking like any other extraskeletal osteoma. This tumor might have been induced
      by circulating stem cells; however, due to autologous bona marrow
      transplantation, this cannot be proven.

PMID- 16639607
TI  - Spectrum of molecular alterations in colorectal, upper urinary tract,
      endocervical, and renal carcinomas arising in a patient with hereditary non
      polyposis colorectal cancer.
AB  - Hereditary nonpolyposis colon cancer (HNPCC) syndrome is the most frequent
      hereditary cancer syndrome predisposing to cancers of various locations,
      especially colon, endometrium, stomach, and upper urinary tract. Carcinomas of
      the kidney parenchyma are not considered as an HNPCC-related tumor. HNPCC tumors
      are characterized by microsatellite instability (MSI) due to a defect in mismatch
      repair (MMR) and carry somatic frameshift mutations in mononucleotide repeats
      within the coding regions of key genes. We report the first case of a papillary
      carcinoma of the kidney in an HNPCC patient who developed carcinomas of the upper
      urinary tract, endocervix, and colon. Whereas the HNPCC-related tumors
      demonstrated MSI phenotype, loss of MSH2 protein expression, and frameshift
      mutations in several of the 13 target genes analyzed, the kidney cancer displayed
      MSS phenotype, normal MMR protein expression, and no frameshift mutation in
      target genes. Our observations do not support the possibility that papillary
      carcinomas are part of HNPCC syndrome.

PMID- 16639608
TI  - Accuracy and precision of perfusion lung scintigraphy versus 133Xe
      radiospirometry for preoperative pulmonary functional assessment of patients with
      lung cancer.
AB  - PURPOSE: This study sought to determine whether (133)Xe-radiospirometry (XRS)
      successfully selects patients able to undergo lung resection without
      postoperative respiratory complications and whether perfusion lung scintigraphy
      (PLS) is likely to provide a similar selection of patients for certain tumour
      stages. METHODS: Two hundred and eighty-four patients with resectable lung cancer
      underwent preoperative assessment of postoperative forced expiratory volume in 1
      s (FEV(1)) by XRS and PLS. Correlations, Bland and Altman analysis and
      contingency tables were used to analyse the difference between the two predictive
      techniques. RESULTS: One hundred and sixty patients underwent lung resection on
      the basis of XRS preoperative testing only. None of them developed respiratory
      insufficiency. Despite a close correlation, the limits of agreement between
      predicted FEV(1) by XRS and PLS exceeded +/-0.3 l/s. For tumour stages T1Nx and
      T2N0, PLS underestimated postoperative FEV(1) whereas it overestimated this
      parameter for stage III. CONCLUSION: XRS accurately selects patients able to
      undergo lung resection without postoperative pulmonary insufficiency. The
      agreement between XRS and PLS is unacceptable. When only PLS is available, higher
      thresholds for patients with stage III cancers and lower thresholds for those
      with stage I cancers should be used to decide on operability.

PMID- 16639609
TI  - PET-measured heterogeneity in longitudinal myocardial blood flow in response to
      sympathetic and pharmacologic stress as a non-invasive probe of epicardial
      vasomotor dysfunction.
AB  - PURPOSE: We investigated whether a myocardial perfusion gradient during
      pharmacologically induced hyperemia also occurred during sympathetic stimulation
      with cold pressor testing (CPT), which commonly induces a paradoxical coronary
      vasoconstriction in individuals with coronary risk factors. METHODS: Myocardial
      blood flow (MBF) was measured in absolute units (ml/g/min) with 13N-ammonia and
      PET at rest, during CPT, and during pharmacologic vasodilation in 59 participants
      with coronary risk factors ("at risk") and in 43 healthy individuals (controls).
      MBF was assessed globally as mean MBF, and in the mid and mid-distal myocardium
      of the left ventricle (LV). A decrease in MBF from mid to mid-distal LV
      myocardium was defined as MBF difference indicative of a perfusion gradient.
      RESULTS: The change in mean MBF to CPT (DeltaMBF) in the at-risk group was
      significantly reduced compared with controls (0.05+/-0.19 vs 0.31+/-0.20
      ml/g/min, p<0.0001), whereas mean MBF during pharmacologic vasodilation in the at
      risk group tended to be lower than in controls (1.72+/-0.71 vs 2.00+/-0.64
      ml/g/min, p=NS). Absolute MBFs during CPT and pharmacologic vasodilation were
      significantly lower in the mid-distal than in the mid LV myocardium, resulting in
      a significant MBF difference in the at-risk group (0.15+/-0.06 and 0.27+/-0.12
      ml/g/min, p<0.0001) that was not observed in controls (0.007+/-0.05 and 0.014+/
      0.10 ml/g/min, p=NS). In the at-risk group there was a significant correlation
      between the difference of mid to mid-distal MBF during CPT and that during
      pharmacologic vasodilation (r=0.43, p<0.004), suggesting functional alterations
      of epicardial vessels as the predominant cause for the observed MBF difference.
      CONCLUSION: The relative decrease in MBF from the mid to the mid-distal left
      ventricular myocardium suggests an intracoronary pressure decline during CPT and
      pharmacologic vasodilation, which is likely to reflect an impairment of flow
      mediated epicardial vasomotor function.

PMID- 16639610
TI  - Partial volume effect correction in SPECT for striatal uptake measurements in
      patients with neurodegenerative diseases: impact upon patient classification.
AB  - PURPOSE: In single-photon emission computed tomography (SPECT) of the
      dopaminergic system, measurements of striatal uptake are useful for diagnosis and
      patient follow-up but are strongly biased by the partial volume effect (PVE). We
      studied whether PVE correction might improve patient classification based on
      binding potential (BP) measurements. METHODS: Patients with a probable diagnosis
      of dementia with Lewy bodies (DLB, 10 patients) or Alzheimer's disease (AD, 13
      patients) were studied by( 123)I-FP-CIT SPECT. SPECT images were reconstructed
      with and without PVE correction. Each patient SPECT scan was also simulated to
      obtain SPECT data whose characteristics were fully known. In addition, 17 SPECT
      scans were simulated with striatal uptake values mimicking pre-symptomatic cases
      of DLB. RESULTS: Without PVE correction, mean putamen BP values were 2.9+/-0.4
      and 0.9+/-0.2 for AD and DLB patients respectively, while with PVE correction,
      they were 8.6+/-1.5 and 1.9+/-0.5 respectively. All patients were properly
      identified as having AD or DLB when considering mean putamen BP measured on their
      real or simulated SPECT scan, with and without PVE correction. All 30 simulations
      mimicking pre-symptomatic DLB and AD patients were accurately classified with PVE
      correction, but without PVE correction 15 mean putamen BP values were in a range
      where AD and DLB could not be distinguished. CONCLUSION: We conclude that putamen
      BP values measured without PVE correction can be used to differentiate probable
      DLB and AD due to the already severe reduction in dopamine transporter levels.
      PVE correction appeared useful for accurate differential diagnosis between AD and
      pre-symptomatic DLB.

PMID- 16639611
TI  - Long lasting effects of unmasking in a feature fusion paradigm.
AB  - In spite of more than 100 years of research, the mechanisms underlying visual
      masking are still unknown. In recent publications, we introduced an unmasking
      paradigm involving the fusion of features that revealed interesting spatial
      characteristics. Here, we investigate the temporal aspects of this paradigm
      showing very long lasting effects that impose serious restrictions on models of
      masking. We used a simple feed-forward neural network model to explain these
      results.

PMID- 16639612
TI  - Preceding stimulus awareness augments offset-evoked potentials: evidence from
      motion-induced blindness.
AB  - Event-related potentials (ERPs) were measured in response to the objective offset
      of a visual disk under two physically similar conditions: (1) visible conditions
      in which the target disk was well perceived and (2) invisible conditions in which
      participants reported to have not seen the target because of motion-induced
      blindness (Bonneh, Cooperman, & Sagi in Nature 411:798-801, 2001).
      Electrophysiological responses to the physical offset of the target disk were
      almost completely absent in the invisible conditions (Experiment 2). In the same
      conditions, the physical offset was almost completely invisible (Experiment 1).
      Results suggest an augmenting function of prior awareness of a stimulus for the
      offset-triggered ERP of that stimulus.

PMID- 16639613
TI  - Perceptual latency priming: a measure of attentional facilitation.
AB  - The present paper reviews recent research on perceptual latency priming (PLP).
      PLP is the relative latency advantage-earlier perception-of a visual stimulus
      that is preceded by another, masked stimulus at its location. The first stimulus
      attracts attention which accelerates perception of the second stimulus. This
      facilitation arises even if the first stimulus is visually backward-masked by the
      second one. The paper summarises research on temporal and spatial properties of
      PLP and the question whether intentions mediate shifts of attention to external
      events. Possible sources of PLP besides visuo-spatial attention are discussed.
      Finally, I give a review of feedforward and reentrant models of PLP and compare
      them to the empirical evidence.

PMID- 16639614
TI  - History of experimental psychology from an Estonian perspective.
AB  - A short review of the development of experimental psychology from an Estonian
      perspective is presented. The first rector after the reopening of the University
      of Dorpat (Tartu) in 1802, Georg Friedrich Parrot (1767-1852) was interested in
      optical phenomena which he attempted to explain by introducing the concept of
      unconscious inferences, anticipating a similar theory proposed by Herman von
      Helmholtz 20 years later. One of the next rectors, Alfred Wilhelm Volkmann (1800
      1878) was regarded by Edwin Boring as one of the founding fathers of the
      experimental psychology. Georg Wilhelm Struve (1793-1864) played an essential
      part in solving the problem of personal equations. Arthur Joachim von Oettingen
      (1836-1920) developed a theory of music harmony, which stimulated his student
      Wilhelm Friedrich Ostwald (1853-1932) to study colour harmony. Emil Kraepelin
      (1856-1926), the founder of modern psychiatry, is by far the most important
      experimental psychologist who has worked in Estonia. His successor Wladimir von
      Tchisch (1855-1922), another student of Wilhelm Wundt, continued Kraepelin's work
      in experimental psychology. The lives of Wolfgang Kohler (1887-1967), who was
      born in Reval (Tallinn), and Oswald Kulpe (1862-1915), who graduated from the
      University of Dorpat, extended the link between the history of experimental
      psychology and Estonia. Karl Gustav Girgensohn (1875-1925), the founder of the
      Dorpat School of the psychology of religion, stretched the use of experimental
      methods to the study of religious experience.

PMID- 16639615
TI  - Utilization of covariation knowledge in source monitoring: no evidence for
      implicit processes.
AB  - In three experiments, a "hidden covariation" (Lewicki, in Journal of Experimental
      Psychology: Learning, Memory, and Cognition, 12, 135-146, 1986) of nonsalient
      stimulus attributes and the source of stimulus information was established to
      test whether implicit knowledge about this correlation influences source memory
      judgments. The source monitoring framework (Johnson, Hashtroudi, and Lindsay, in
      Psychological Bulletin, 114, 3-28, 1993) postulates heuristic and strategic
      judgment processes in source attributions. A multinomial model analysis
      disentangled memory and guessing processes. While there were large strategic
      guessing biases involving explicit knowledge in all experiments, there was no
      evidence for the use of implicit covariation knowledge. Only participants who
      were later able to verbalize the covariation had shown corresponding biases
      during the source memory test, suggesting that implicit covariation knowledge
      plays no prominent role in the reconstruction processes in source monitoring.

PMID- 16639616
TI  - Small Rho GTPases are important for acinus formation in a human salivary gland
      cell line.
AB  - Rho GTPases participate in a wide variety of signal transduction pathways
      regulating the actin cytoskeleton, gene expression, cellular migration and
      proliferation. The aim of this study was to evaluate the role of Rho GTPases in
      signal transduction pathways during acinus formation in a human salivary gland
      (HSG) cell line initiated by extracellular matrix (ECM; Matrigel) alone or in
      combination with epidermal growth factor, basic fibroblast growth factor and
      lysophosphatidic acid (LPA). Immunohistochemical and Western blotting analyses
      showed that HSG cells contained RhoA, RhoB, Rac1 and Cdc42 proteins. All growth
      factors enhanced the effects of ECM on acinus formation, in a pathway dependent
      on PI3-kinase and Rho GTPases. The role of ROCK, a major RhoA effector, seemed
      limited to cortical actin polymerization. LPA stimulated cell migration and
      acinus formation in a PI3-kinase-independent pathway. The results suggest that
      Rho proteins are important for epithelial-mesenchymal interactions during
      salivary gland development.

PMID- 16639617
TI  - Appearance of cuboidal cells in relation to salinity in gills of Fundulus
      heteroclitus, a species exhibiting branchial Na+ but not Cl- uptake in
      freshwater.
AB  - Fundulus heteroclitus (killifish) is a model organism for ionoregulatory studies,
      particularly because of its opercular epithelium, although the gills are the
      major sites of ion exchange. Whereas Na+ and Cl- are excreted through the gills
      in seawater (SW), the killifish is unusual in taking up only Na+ and not Cl- at
      the gills in freshwater (FW). We describe morphological changes in the branchial
      epithelium following transfer from an acclimation medium of 10% SW to 100% SW or
      FW. In 10% SW, mitochondria-rich cells resemble typical seawater chloride cells
      (SWCCs) with accessory cells. After transfer to 100% SW, no change occurs in
      pavement cell (PVC) morphology or mitotic rate (measured by bromo-deoxyuridine
      technique), although the density of SWCC apertures increases several fold because
      of the uncovering of buried SWCCs by PVCs, in accord with increased rates of Na+
      and Cl- efflux. After transfer to FW, PVC morphology remains unchanged, but SWCCs
      and accessory cells are quickly covered by PVCs, with many undergoing apoptosis
      or necrosis. The mitotic rate doubles by 10-14 h but typical freshwater chloride
      cells (FWCCs) do not appear. Instead, a wedge-shaped cell type that is moderately
      rich in apically oriented mitochondria, with a large ovoid nucleus, thin
      cytoplasmic layer, paucity of vesicular-tubular network, and variably villous
      surface rapidly (by 3 h) and progressively appears in the filament epithelium, by
      both uncovering and mitosis. This cell type is similar to that recently
      identified as the site of Na+ uptake in the FW trout gill. We propose the new
      term "cuboidal cell" for this cell, based on its morphology, to avoid confusion
      with traditional terminology (of PVC). We hypothesize that the cuboidal cells are
      the sites of active Na+ uptake in FW F. heteroclitus and suggest that the lack of
      Cl- uptake is attributable to the absence of typical FWCCs previously described
      in teleosts.

PMID- 16639619
TI  - ["Scientific Evidence": or: "The methodical attraction of the lawnmower"].

PMID- 16639620
TI  - [The vascular Parkinson syndrome].

PMID- 16639621
TI  - Correlation between optical coherence tomography and autofluorescence in acute
      posterior multifocal placoid pigment epitheliopathy.
AB  - PURPOSE: To report a case of bilateral acute posterior multifocal placoid pigment
      epitheliopathy (APMPPE) evaluated by optical coherence tomography (OCT), fundus
      autofluorescence (AF) and microperimetry, both in the acute phase and after
      resolution of symptoms. METHODS: Complete ophthalmological evaluation, including
      fluorescein angiography, OCT, AF, and microperimetry upon presentation and 1
      month later, after lesions have subsided. An attempt to correlate the findings on
      presentation and changes after resolution is performed using the results of these
      new investigational techniques. RESULTS: APMPPE showed hyperreflectance in OCT at
      the level of the outer retinal layers, without increase in retinal thickness. AF
      revealed early decreased fluorescence due to a masking effect, and later reveals
      increased fluorescence after resolution of OCT findings. Function is disturbed at
      the lesion sites, as shown by microperimetry, and later returns to near normal
      values on microperimetry. CONCLUSION: APMPPE shows outer retinal layers changes
      on OCT, which resolve totally after subsidence of the acute phase. AF shows areas
      of increased fluorescence after resolution, with near normal return of function
      on microperimetry.

PMID- 16639622
TI  - Changes in the crystalline lens resulting from insertion of a phakic IOL (ICL)
      into the porcine eye.
AB  - BACKGROUND: Insertion of a phakic IOL offers these advantages: the corneal
      optical zone is not dissected or resected; preservation of the crystalline lens
      results in preservation of the accommodation force; and since the phakic IOL is
      removable, any error or change in refraction can be countered by exchanging it.
      However, the cause of secondary cataracts has never been clarified or discussed
      to date. METHODS: The following ICL lenses were inserted under general
      anaesthesia into 20 eyes of ten 3-month-old miniature pigs: a minus lens without
      holes into five eyes, a plus lens in two eyes, a minus lens with four holes
      around the lens haptics in three eyes, and a minus lens with a central hole in
      the optic in three eyes; and seven eyes were used as controls. The anterior
      segments were then photographed 1 week, 1 month and 3 months after surgery. At 3
      months after surgery, Evans blue (EB) was infused into the vitreous under general
      anaesthesia, and after 30 min, the eyeball was enucleated, fixed and examined.
      RESULTS: In the case of the ICL without holes, the anterior subcapsular opacities
      were observed in all the eyes, and the anterior surfaces of the crystalline
      lenses were not stained with EB. Use of the ICL with four holes around the lens
      haptics resulted in light staining of the anterior surface of the crystalline
      lens, but the anterior subcapsular opacities observed were mild. As for the ICL
      with a hole in the centre of the optic, the anterior surface of the crystalline
      lens was stained and no anterior subcapsular opacities were observed. CONCLUSION:
      The results suggested that the insertion of an ICL brings about a change in the
      dynamics of the intraocular aqueous humour, reducing its circulation to the
      anterior surface of the crystalline lens. This is considered to cause a metabolic
      disturbance of the crystalline lens, resulting in anterior subcapsular
      opacification.

PMID- 16639623
TI  - Pars plana vitrectomy and panretinal photocoagulation combined with
      trabeculectomy for successful treatment of neovascular glaucoma.
AB  - BACKGROUND: Treatment of neovascular glaucoma (NVG) must be focused on the
      reduction of intraocular pressure (IOP) and prompt application of pan retinal
      photocoagulation (PRP). A combination of complete PRP during vitrectomy with
      trabeculectomy should theoretically be a better method to lower the IOP rapidly
      in eyes with NVG. The purpose of our study is to assess the efficacy of combining
      pars plana vitrectomy and PRP with trabeculectomy assisted by mitomycin C (MMC)
      on NVG eyes secondary to diabetic retinopathy. METHODS: Twenty-five eyes with NVG
      associated with diabetic retinopathy had pars plana vitrectomy, followed by PRP
      and trabeculectomy with MMC. The eyes were divided into two groups: nine eyes
      with vitreous hemorrhage, fibrovascular membrane and/ or retinal detachment were
      placed in the Proliferation group; and 16 eyes without vitreous hemorrhage,
      fibrovascular membrane, or retinal detachment were placed in the PC
      (photocoagulation) group. These eyes had vitrectomy performed so that PRP could
      be safely performed from ora to ora. The surgical outcome in the two groups was
      assessed by Kaplan-Meier survival analysis. The criteria for success were a
      postoperative intraocular pressure (IOP) < or =21 mmHg and a preservation of
      light perception. RESULTS: In the Proliferation group, Kaplan-Meier life-table
      analysis showed that the success rate was 55.6% after 1 year and 18.5% after 2
      years. The success rate in the PC group was 81.2% from 1 to 3 years after
      surgery. The surgical outcome was significantly better in the PC group than in
      the Proliferation group (P=0.009). In the Proliferation group, four eyes had
      preoperative vitreous hemorrhage, three eyes had a fibrovascular membrane, and
      two eyes had a retinal detachment. Three of four eyes with vitreous hemorrhage
      achieved good IOP control. On the other hand, the IOP of all eyes with retinal
      detachment and fibrovascular membrane were not lowered significantly.
      CONCLUSIONS: Complete PRP combined with trabeculectomy with MMC can effectively
      reduce the elevated IOP in eyes with NVG. However, this combined treatment is not
      effective in eyes with proliferative membranes and retinal detachments.

PMID- 16639624
TI  - Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong.
AB  - We report a multicenter study of Chinese children in Hong Kong with systemic
      lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled
      the ACR criteria, had significant proteinuria or casturia, were Chinese and
      younger than 19 years and had been diagnosed with SLE between January 1990 and
      December 2003. Investigators in each center retrieved data on clinical features,
      biopsy reports, treatment and outcome of these patients. There were 128 patients
      (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with
      multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti
      dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO
      Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%)
      patients, respectively. The clinical severity of the nephritis did not accurately
      predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years
      (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from
      lupus flare, one from cardiomyopathy, two from infections). Four patients had
      endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end
      stage renal failure occurred in the Class IV nephritis group. Chronic organ
      damage was infrequent in the survivors. The actuarial patient survival rates at
      5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV
      nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were
      91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the
      Chinese SLE children in the present study are comparable to those of other
      published studies.

PMID- 16639625
TI  - In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis.
AB  - OBJECTIVE: To examine in vivo time-course changes in macromolecular composition
      of articular cartilage in two surgical models of osteoarthritis (goat: meniscal
      transection and cartilage incision; rabbit: medial meniscectomy). DESIGN:
      Collagen integrity and proteoglycan (PG) content were evaluated in both models by
      magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate
      k(m) for the exchange process between the bulk water and water bound to collagen
      was determined as a marker of the collagen network. Local changes in cartilage
      fixed charge density, i.e., where PGs are depleted, were derived from T(1)
      relaxation maps as obtained after an infusion of Gd(DTPA)(2-), a paramagnetic
      agent. RESULTS: In the goat model, the MT rate constant k(m) was significantly
      higher at 2 weeks post surgery, a possible sign of cartilage swelling, then
      decreased below baseline values, most likely indicative of disruption in the
      collagen framework. Meanwhile, post-Gd(DTPA)(2-) MRI acquisition indicated a
      significant and sustained loss of PGs. The rabbit model produced milder lesions.
      Although the difference was non-significant, k(m) steadily decreased in response
      to the surgical insult while kinetics of Gd(DTPA)(2-) uptake, after reaching a
      peak level at 6 weeks, were back to normal values after 12 weeks. CONCLUSION: In
      the goat model, joint instability and cartilage damage was a permanent trigger
      for cartilage degeneration producing MRI changes. However, biomechanical stress
      due to partial medial meniscectomy in knees of mature rabbits produced only mild,
      focal lesions and PG depletion that was partially reversible. This proof-of
      concept study identified MT and T(1) parameters as useful surrogate markers in
      animal models of osteoarthritis.

PMID- 16639626
TI  - Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct
      from osteoid osteoma and osteoblastoma, radiologically simulating a vascular
      tumor.
AB  - Two adult patients are described with multifocal osteolytic lesions
      radiologically simulating a vascular tumor. One patient had multiple bones
      involved. Histologically, the individual lesions had the features of the nidus of
      osteoid osteoma/osteoblastoma. A review of the English language medical
      literature yielded only one other reported case with similar features. The
      process is designated as osteoblastomatosis to indicate its bone-forming
      character, prominent osteoblast proliferation, and multiplicity. The cases are
      distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and
      from benign and malignant vascular tumors.

PMID- 16639627
TI  - [Syncope with transient paresis. Lipoma of the tuber cinereum].

PMID- 16639628
TI  - Aplasia cutis congenita of the scalp: is there a better treatment strategy?
AB  - BACKGROUND: Aplasia cutis congenita (ACC) is a rare disease of unknown etiology,
      involving any site of the body. The scalp is the most frequent location, followed
      by the forearms, knees, both sides of the trunk, and neck, in decreasing order of
      frequency. Superficial lesions may heal spontaneously and seldom result in
      morbidity or mortality. However, in patients with large scalp and skull defects,
      there are risks of infection and bleeding. Conservative treatment has been
      described and advocated, but some authors have highlighted the disadvantages of
      this treatment modality. On the other hand, several authors claim that aggressive
      surgical treatment has an important role for large defects. MATERIALS AND
      METHODS: In this paper, we report three newborns with ACC of the scalp, two large
      defects and a medium one, respectively, treated conservatively and surgically.
      CONCLUSION: The management of ACC of the scalp is still controversial. Our series
      suggests that conservative treatment should be performed for initial management
      in newborns.

PMID- 16639629
TI  - Spontaneous regression of optic pathways gliomas in three patients with
      neurofibromatosis type I and critical review of the literature.
AB  - CASE REPORTS: The authors report their experience about three children (two
      girls, one boy; average age 1.6 years) with a spontaneous regression of optic
      gliomas. All of them had a previous diagnosis of neurofibromatosis type 1 (NF 1).
      None of them underwent surgery or biopsy nor received chemotherapy or
      radiotherapy. The complete regression was documented by MRI scans performed
      during a mean follow-up of 6.3 years. LITERATURE REVIEW: Moreover, the authors
      analyze the features of the 16 cases previously reported in English literature of
      spontaneously regressed optic gliomas with an overview of the different
      therapeutic strategies. The knowledge that this kind of tumor, particularly in
      young patients, may regress is important in the decision of the best therapeutic
      approach.

PMID- 16639630
TI  - High tibial osteotomy that does not cause recurrence of varus deformity for
      medial gonarthrosis.
AB  - It is widely accepted that high tibial osteotomy (HTO) is an effective surgical
      treatment for medial gonarthrosis. However, long-term follow-up studies have
      revealed that the clinical results deteriorate over time and varus deformity
      often recurs. We performed barrel-vault osteotomy in HTO with a correction angle
      that did not cause arthritic progression in the medial compartment of the knee or
      recurrence of varus deformity. Thirty patients (44 knees) were followed
      clinically and radiographically for a minimum of 10 years (average, 11.4 years).
      We aimed for an average postoperative femorotibial angle (FTA) of 165.3 degrees
      (range, 162-169 degrees ) according to our method using a correction angle chosen
      on the basis of the so-called Mikulicz's mechanical axis. The clinical results
      were good in 30 (68.2%) knees, fair in 7 (15.9%) and poor in 7 (15.9%). Arthritic
      progression in the medial compartment was only found in 1 (2.3%) knee, while in
      the lateral compartment it was found in 17 (38.6%) knees. Of the knees with
      arthritic progression in the lateral compartment, six (35.3%) were classified as
      poor. The average postoperative FTAs were 164.3 degrees at 1 year, 164.0 degrees
      at 5 years and 163.5 degrees at 10 years after the operation, indicating that the
      knees tended to become slightly valgus over time. The clinical results were not
      poor after slightly overcorrected osteotomy was performed. Since overcorrection
      tended to occur, when the preoperative lateral tibial thrust was severe, HTO is
      not a good indication for such cases.

PMID- 16639631
TI  - Toxocara canis larvae viability after disinfectant-exposition.
AB  - The effect of three routinely used disinfectants on the embryonary development of
      Toxocara canis eggs was evaluated both in vivo and in vitro. In the in vitro
      experiment, T. canis eggs were treated with the ethanol, sodium hypochlorite, and
      one commercial mix of benzalconium chloride and formaldehyde, and the embryonary
      development was assessed. After a period of 24 days incubation, ethanol was the
      best disinfectant because it prevented the development of the T. canis larvae 2
      in the eggs, and sodium hypochlorite caused degeneration in 50% eggs. By using
      the commercial mix, 25% T. canis eggs developed to 2nd stage larvae. In the in
      vivo experiment, the embryonated eggs treated with the disinfectants were
      inoculated to mice, and their brain tissues were examined for larval presence on
      the 24th day postinfection. In addition, a control group was set up for
      comparison with the infected groups. No injury or T. canis larvae were observed
      in mice infected with sodium hypochlorite-treated eggs, opposite to that recorded
      in the animals infected with the commercial disinfectant-treated eggs. These
      results showed that both ethanol and sodium hypochlorite are very appropriate
      because of their full efficacy against infective T. canis eggs. Disinfection of
      kennels, animal shelters, cages, and veterinary clinics with one of these
      products to eliminate T. canis eggs and to avoid contamination is strongly
      recommended.

PMID- 16639632
TI  - The complete sequence of the genome of Humulus japonicus latent virus.

PMID- 16639633
TI  - Complete nucleotide sequences of three dsRNA segments from Raphanus sativus-root
      cv. Yidianhong [corrected] with leaf yellow edge symptoms.
AB  - The two minor dsRNA bands, previously detected in symptomatic leaves of Raphanus
      sativus-root cv. Yidianhong [corrected] were subjected to further analysis. cDNA
      cloning and sequencing revealed that the smaller of the two dsRNA bands is
      actually a doublet consisting of two co-migrating dsRNA segments and the
      resulting three segments were designated as RasR 3, RasR 4, and RasR 5. RasR 3
      was 1717 bp in length and potentially encoded a protein of about 55.3 kDa,
      containing all of the six conserved motifs shared by the RNA dependent RNA
      polymerases of members of the family Partitiviridae. RasR 4 and RasR 5, which co
      migrated in the 5% polyacrylamide gel, were 1521 and 1485 bp in length and each
      encoded a putative protein of unknown function. Their molecular masses, as
      calculated from the deduced amino acid, were 38.2 and 38.8 kDa, respectively. The
      5' UTRs of all three segments shared regions of high sequence similarities, but
      were distinct from those of the RasR 1 and RasR 2. Taken together, these results
      along with those described in the previous report, suggest that more than one
      partitivirus was co-infecting radish leaves.

PMID- 16639637
TI  - Bronchial artery aneurysm embolization with NBCA.
AB  - We present a case of asymptomatic bronchial artery aneurysm that formed a fistula
      with part of the pulmonary artery (there was no definite fistula with the
      pulmonary vein). We were able to catheterize the feeding vessel but could not
      reach the aneurysm. We therefore injected a mixture of N-butyl-2-cyanoacrylate
      (NBCA; Histoacryl, B. Braun, Melsungen, Germany) and iodized oil (Lipiodol;
      Guerbet, Aulnay-sous-Bois, France) from the feeding vessel. The fistula,
      aneurysm, and feeding vessel were almost totally occluded. After embolization,
      the patient coughed a little; there were no other definite side effects or
      complications. One and 3 months later, on chest CT, the aneurysm was almost
      completely occupied with hyperattenuating NBCA-Lipiodol embolization. NBCA is a
      liquid embolization material whose time to coagulation after injection can be
      controlled by diluting it with Lipiodol. It is therefore possible to embolize an
      aneurysm, feeding vessels, and efferent vessels (in our case, it was a fistula)
      by using an NBCA-Lipiodol mixture of an appropriate concentration, regardless of
      whether the catheter can reach the aneurysm or not.

PMID- 16639651
TI  - Routine shunting is a safe and reliable method of cerebral protection during
      carotid endarterectomy.
AB  - The purpose of this report is to describe the perioperative and long-term
      outcomes of standard carotid endarterectomy (CEA) with general anesthesia,
      routine shunting, and patching and to show that routine shunting is a safe and
      reliable method of cerebral protection. Between January 1998 and December 2004,
      700 patients attending our Department of Vascular Surgery underwent 786 CEAs
      performed using a standardized technique. Forty-four patients were excluded from
      the analysis because they underwent combined CEA and coronary artery bypass
      grafting, so the analysis is based on the results of 742 CEAs in 656 patients (86
      bilateral CEAs). The strict surgical protocol included general anesthesia and
      standard carotid bifurcation endarterectomy with routine shunting (Javid's shunt)
      and Dacron patching. The Javid shunts were easily inserted in 738 cases (99.4%)
      but could not be used in four cases (0.5%) because of the presence of a very
      small internal carotid artery. The mean ischemic time required to insert the
      shunt and complete the suture was 4.7 min (+/-1.15), and the mean time to perform
      the endarterectomy was 34.3 min (+/-6.7). The mean follow-up was 24.4 months (+/
      17.3). Overall 30-day mortality was 0.1% (one patient) due to a contralateral
      major stroke. The 1-month perioperative neurological complication rate was 0.7%,
      with three major and two minor strokes. The cumulative stroke and death rate was
      0.8%. Preoperative symptoms such as hypertension, contralateral occlusion, or an
      age of more than 80 years were not independent risk factors for perioperative
      stroke. In the long-term follow-up, Kaplan-Meier analysis indicated an estimated
      5-year stroke-free rate of 98.0%. There were eight cases (1%) of >70% restenosis
      (four cases) or thrombosis (four cases) of the operated internal carotid artery
      during the follow-up in asymptomatic patients: in four cases, carotid stenting
      due to >70% restenosis led to good results. The Kaplan-Meier estimate of the
      restenosis-free rate was 97.8%. The combined stroke and mortality rate of 0.8%,
      and the restenosis rate of 1% support the argument that standard CEA performed
      with routine shunting as brain protection leads to excellent early and long-term
      results.

PMID- 16639661
TI  - [Tumors of the eyelids].

PMID- 16639662
TI  - [Comments on current therapeutic possibilities for neovascular age-related macula
      degeneration].
AB  - BACKGROUND: New treatments for neovascular age-related macular degeneration have
      emerged recently, and data from phase III clinical trials are now available. In
      the light of these data, expert guidance appears prudent to aid ophthalmologists
      to select the most appropriate therapeutic strategy for the individual patient.
      METHODS: Therapeutic options discussed include laser photocoagulation, PDT with
      verteporfin, triamcinolone and its possible combination with PDT, anecortave
      acetate, pegaptanib and ranibizumab. Treatment principles are described and
      relevant clinical data summarized. RECOMMENDATIONS: Extrafoveal classic CNVs
      should be treated with thermal laser coagulation. For subfoveal lesions with
      predominantly classic CNV, or occult forms with non-classic CNV, a lesion size <
      or = 4 macular photocoagulation study (MPS) disc areas (DA) and recent disease
      progression, PDT with verteporfin is a safe and efficacious treatment. For the
      remaining subtypes, VEGF inhibitors (pegaptanib, ranibizumab, bevacizumab) for
      intravitreal use are now available as therapeutic alternatives. The results of
      the phase III studies for pegaptanib and ranibizumab, however, are not
      comparable, in particular with reference to the outcomes in the control groups.
      Since bevacizumab and ranibizumab are comparable in their pharmacological profile
      bevacizumab may be an alternative in the off-label treatment of neovascular AMD.
      Reliable data concerning safety and efficacy for bevacizumab, however, are not
      available and there are no data on combination therapies. The switch to
      alternative treatment modalities should be considered in particular when the
      first line treatment is ineffective. CONCLUSIONS: These recommendations provide
      evidence-based guidance for non-surgical therapies in the management of
      neovascular AMD. Revisions of the recommendations will be published when new data
      become available.

PMID- 16639663
TI  - [Visual distortions and depersonalization-de-realization syndrome].
AB  - Disturbances of visual perception like micropsia, macropsia, teleopsia, pelopsia,
      metamorphopsia or loss of stereoscopic depth perception are usually considered in
      ophthalmology as symptoms of retinopathy, especially maculopathy or disorders of
      binocularity. Differential diagnostic considerations include disorders like
      migraine and epilepsy but not the visual disturbance pertaining to the
      depersonalization-de-realization syndrome, although the above-mentioned symptoms
      are more prevalent in this psychogenic disorder. This article gives a review of
      depersonalization-de-realization in order to enable the ophthalmologist to
      include this syndrome into his diagnostic considerations.

PMID- 16639664
TI  - [Ultrasound of the upper eyelid to evaluate tarsal curvature in facial palsy].
AB  - BACKGROUND: Treatment of paralytic lagophthalmos involves surgical repair,
      requiring exact knowledge of eyelid anatomy. While there are extensive studies on
      anatomical eyelid measurements in healthy eyes, no data exist on the changes in
      the functional anatomy of the upper eyelid in paralytic lagophthalmos. The aim of
      this study, was to examine by ultrasound the upper lid tarsus during changes in
      the patient's line of vision, and to answer the question of whether there are
      changes in the curvature radius of the tarsus, caused by facial paralysis with
      resultant lagophthalmos. MATERIAL AND METHODS: Two groups were formed. The first
      group consisted of 50 subjects with healthy eyes, and the second contained 47
      patients with paralytic lagophthalmos. The upper lid tarsal radius, when looking
      straight ahead and in the abducted position, was determined by ultrasound with a
      7.5 MHz scanner in the non-contact mode, and then compared statistically.
      RESULTS: Both groups showed a highly significant difference in the tarsus
      curvature, when looking straight ahead and in the abduction position. While there
      was no significant difference between both groups in the abduction position, they
      differed significantly when looking straight ahead. Also, a significant
      difference was noted, between the eyes of healthy subjects and the healthy eye in
      patients with facial palsy. CONCLUSION: The changes in curvature of the tarsal
      plate, when looking straight ahead, can be explained by the loss of tone in the
      paralyzed Orbicularis Occuli muscle. This means, that in addition to the
      lagophthalmos resulting from facial paralysis, changes occur in the functional
      anatomy of the upper eyelid, which must be considered during surgical correction.
      Additionally, the physiological loss of tone of the upper eyelid tarsal plate,
      which comes with age, has a certain influence.

PMID- 16639665
TI  - [Development of visual acuity and refraction in deep lamellar and penetrating
      keratoplasty (KPL)].
AB  - BACKGROUND: Deep lamellar KPL can be considered as an alternative for penetrating
      KPL in pathologies of corneal stroma, because there is no risk of decompensation
      of the endothelium or corneal rejection. Nevertheless, it is well know in
      lamellar keratoplasty that scars may occur in the interface which can limit the
      final visual acuity. In a retrospective study we compared the postoperative
      development of visual acuity and refractive values in deep lamellar keratoplasty
      with a penetrating procedure. PATIENTS AND METHODS: 16 consecutive patients (mean
      age 48 years) with corneal stroma pathologies such as corneal ulcer, alkali burn
      and keratoconus underwent deep lamellar KPL. The control group consisted of 38
      patients (mean age 42 years) with keratoconus who received a penetrating
      keratoplasty. Visual acuity and subjective spherical and cylindrical values of
      the refraction were evaluated preoperatively and after 6 weeks, 6 months and 1
      year. RESULTS: The mean postoperative visual acuity (VA), spherical (SV) and
      cylindrical (CV) values of the deep lamellar group (results of the control group
      in brackets) were at 6 weeks VA = 0.24 +/- 0.24 (0.37 +/- 0.23), SV = 0.325 +/-
      5.3 dpt, CV = - 1.66 +/- 0.67 dpt (- 3.08 +/- 1.93 dpt), after 6 months VA = 0.38
      +/- 0.28 (0.53 +/- 0.31), SV = - 3.0 +/- 4.42 dpt (0.33 +/- 1.93 dpt), CV = -
      2.57 +/- 2.03 dpt (- 2.35 +/- 1.32 dpt) and after 1 year VA = 0.41 +/- 0.27 (0.57
      +/- 0.26), SV = - 2.57 +/- 4.62 dpt (0.17 +/- 3.98 dpt), CV = - 2.75 +/- 1.25 dpt
      (- 0.34 +/- 1.86 dpt). There was no significant difference in all the parameters
      between the two groups. CONCLUSIONS: As the good functional results of deep
      lamellar KPL are comparable to those of penetration KPL and the risk of
      endothelial decompensation or rejection is lower in a lamellar procedure, we
      suggest the use of a deep lamellar KPL in patients with an intact endothelium.

PMID- 16639666
TI  - [Systemic bias in the photographic assessment of the first purkinje image].
AB  - BACKGROUND: The growing popularity of digital imaging leads to an increasing
      number of photos transferred by parents via E-mail to an ophthalmologist, showing
      a child with a displacement of corneal reflections. This must not necessarily
      lead to the diagnosis of manifest strabismus. MATERIALS AND METHODS: The
      displacement of the first Purkinje image is demonstrated by moving the flash of a
      digital camera sideways from the objective. Photographs were taken at a distance
      of 0.6 m while the healthy test subject was looking into the camera. Flashlight
      was displaced gradually up to 20 cm to the left side of the objective. The
      resulting displacement of the corneal reflections was measured after transferring
      the photos to a computer. RESULTS: Displacement of the source of light by 10 cm
      resulted in a displacement of the first Purkinje image of about 1 mm, i. e.,
      about 0.1 mm per degree. CONCLUSIONS: Displacement of corneal reflection was 0.1
      mm per degree. Asymmetry of corneal reflections is twice as much, since the
      corneal reflections are displaced in the same direction on both eyes. Lateral
      displacement of the flash from the objective of the camera by 2.5 cm results in
      an asymmetry of 0.5 mm, thus suggesting a squint angle of 6 degrees. Vice versa,
      a real strabismus can be masked. This bias can be avoided by using the camera
      with the flash above the objective in relation to the patient's interpupillar
      axis. Nevertheless, it is impossible to diagnose or to exclude a microstrabismus
      by this method itself, because an angle kappa, if it is different on both eyes,
      can also mimic or mask a manifest strabismus.

PMID- 16639667
TI  - [Cataract surgery in patients with end-stage glaucoma].
AB  - BACKGROUND: The purpose of this study was to assess the benefit of cataract
      surgery in patients with advanced cataract and glaucoma. METHODS: In a
      prospective study, we investigated 12 consecutive patients (12 eyes). Inclusion
      criteria were the diagnosis of cataract and end-stage glaucoma with a cup-disc
      ratio (CD) of 0.9-1.0 and marked visual field defects with partially preserved
      central function. Preoperatively, at the third postoperative day and after 6
      months (2-11 months), the visual acuity (V), the intraocular pressure (IOP), the
      number of antiglaucomatous drugs and the visual fields were assessed.
      Furthermore, the surgical procedure and possible complications were noted. In all
      patients cataract surgery was performed with topical anaesthesia. RESULTS: 10
      patients were treated with cataract surgery alone, whereas 2 patients underwent
      combined cataract and glaucoma surgery. The mean visual acuity improved
      significantly from 0.3 to 0.5 (p = 0.007). Additionally a significant intraocular
      pressure reduction of 4.4 mm Hg (p = 0.007) was observed. The number of
      antiglaucomatous drugs decreased from 1.5 preoperatively to 0.8 postoperatively.
      The mean deviation (MD) improved from -27.5 dB up to -26.4 dB (p = 0.036) after 6
      months. CONCLUSION: Patients with progressive cataract and end-stage glaucoma can
      benefit from cataract surgery. Although marked visual field defects were present,
      an increase in visual acuity as well as a decrease of intraocular pressure may be
      achieved without worsening of the visual fields.

PMID- 16639668
TI  - [Laser surgery for glaucoma: excimer-laser trabeculotomy].
AB  - BACKGROUND: Excimer-laser trabeculotomy (ELT) is a new, minimally invasive
      surgical procedure for the treatment of open-angle glaucoma that can easily be
      combined with cataract surgery. We herein report our experience with ELT as a
      stand-alone procedure and ELT plus cataract surgery. METHODS: A total of 135
      patients with open-angle glaucoma (n = 128) or ocular hypertension (n = 7) (M : F
      = 49 : 86, mean age 69.7 +/- 1.2 years) were included in this study. Patients
      were divided into 2 groups: a) ELT as a stand-alone procedure (n = 75), b)
      combined cataract and ELT procedure (n = 60). Both groups were further divided
      into 2 subgroups: 1) Preoperative IOP > 22 mmHg, 2) Preoperative IOP < or = 22
      mmHg. Kaplan-Meier survival curves were calculated. Success criterion was 20 %
      decrease of IOP and IOP < or = 21 mmHg and postoperative IOP-lowering medication
      < or = preoperative IOP-lowering medication. Follow-up time was 1 year. RESULTS:
      Group a) ELT, 1) preoperative IOP > 22 mmHg, 2) preoperative IOP < or = 22 mmHg:
      Kaplan-Meier survival curves showed a success rate of 57 % in subgroup 1 and of
      41 % in subgroup 2. Group b) Combined cataract and ELT procedure, 1) preoperative
      IOP > 22 mmHg, 2) Preoperative IOP < or = 22 mmHg: success rate was 91 % in
      subgroup 1 and 52 % in subgroup 2. CONCLUSION: ELT is a promising IOP-lowering
      technique both as a stand-alone procedure and in combination with cataract
      surgery. It is especially suitable for patients with high preoperative IOP
      levels.

PMID- 16639669
TI  - [Healthy optic discs with large cups--a diagnostic challenge in glaucoma].
AB  - BACKGROUND: Healthy optic discs with large cups are often characterised to be
      glaucomatous in automated, morphometric analysis. The aim of this study was to
      investigate the variables of laser scanning tomography (LST) and nerve fibre
      polarimetry of these disks in comparison to small and normal sized disks.
      METHODS: 117 eyes (age 49.3 +/- 14.6 years) with healthy, non-atrophic disks (md
      = 0.8 dB, Tensio 14.3 +/- 2.5 mmHg) of the Erlangen Glaucoma Registry were
      clinically examined. Morphometry was performed both by planimetry and the HRT I
      (Heidelberg Engineering, Dossenheim, version 2.01) and with the GDx FCC (Laser
      Diagnostics, San Diego). 63 eyes initially referred for a large cup were compared
      to 54 normal eyes. All measurements were analysed globally and in four sectors
      according to Jonas. RESULTS: The disc area of discs with large cups was
      significantly larger than that for the normals (3.1 +/- 5.3 vs. 2.2 +/- 4.2 mm
      (2)). Both the multivariate analysis of the HRT and the GDx revealed a
      significant correlation with total disk area (R = 0.34, p = 0.0001), with a high
      percentage of false positive glaucoma eyes among large disks. Cup area and volume
      showed, in contrast to rim volume and rim area, a significant correlation (R =
      0.76, p = 0.0001) with the disc size. Thickness of retinal nerve fibre layer
      measurements both in HRT and GDx showed higher values for larger disc size with
      steeper cup measurements. The vertical diameter of the cup increased in
      comparison to the horizontal to a higher extent with increasing disc size.
      CONCLUSIONS: By the pronounced enlargement of cup measurements, decreasing nerve
      fibre thickness values and decreasing ratio of temporal-to-inferior width of the
      neuroretinal rim, large disks may easily be detected as false glaucomatous by
      morphometric analysis systems. A better presentation of large discs in a
      normative database and integration of sectors and disc area in a multivariate
      analysis may improve the diagnostic abilities of automated morphometric disk
      analysis.

PMID- 16639670
TI  - [Parapapillary autofluorescence as indicator for glaucoma].
AB  - BACKGROUND: A pronounced fundus autofluorescence (lipofuscin) occurs in eyes with
      AMD. Parapapillary lipofuscin accumulation in the retinal pigment epithelial
      cells was observed in eyes with advanced glaucoma histologically. The aim of this
      study was to evaluate the parapapillary autofluorescence (PAF) in vivo in healthy
      eyes (controls), and in eyes with primary open angle glaucoma (POAG),
      pseudoexfoliation glaucoma (PSXG) or normal tension glaucoma (NTG). PATIENTS AND
      METHODS: Controlled cross-sectional analysis was performed on 281 consecutive
      eyes (98 controls, 95 POAG, 32 PSXG, 56 NTG). Eyes with fundus pathologies were
      excluded. The confocal scanning laser ophthalmoscope HRA II (Heidelberg Retina
      Angiograph II) was used after lipofuscin-excitation with an argon blue laser (488
      nm) to detect PAF in the spectrum above 500 nm. PAF area and PAF distance to the
      optic nerve head were analyzed using the HRA standard software. Two experienced
      ophthalmologists classified independently the stage of glaucomatous optic nerve
      head atrophy (GONHA) using 15 degrees fundus photographs. RESULTS: Vital optic
      nerve heads had smaller PAF areas (stage 0: 0.07 +/- 0.09 mm (2)) in contrast to
      advanced stages of GONHA (stages 1 to 4: 0.27 +/- 0.46 mm (2); p < 0.001;
      logistic regression Cox and Snell: r = 0.7; p = 0.015). The PAF distance to the
      optic nerve head was lower in controls (0.12 +/- 0.08 mm) than in eyes with POAG,
      PSXG, or NTG (0.25 +/- 0.21 mm, Bonferroni: p < 0,004). The PAF area correlated
      significantly with the stage of GONHA (stage 1: 0.23 +/- 0.23 mm (2), stage 2:
      0.24 +/- 0.19 mm (2), stages 3 and 4: 0.34 +/- 0.73 mm (2), p < 0.01). No
      significant difference of PAF area was found between the glaucoma types. However,
      the distance between PAF and optic nerve head was higher in POAG (0.28 +/- 0.26
      mm) than in NTG (0.24 +/- 0.07 mm) or in PSXG (0.18 +/- 0.07 mm, Bonferroni: p <
      0.03). CONCLUSIONS: A pronounced fundus autofluorescence was detected as a sign
      of increased lipofuscin accumulation in the parapapillary atrophic zone of eyes
      with POAG, PSXG, and NTG in contrast to controls. The PAF analysis may provide an
      indicator for glaucomas in the future.

PMID- 16639671
TI  - [Value of different measurements of the preoperative visual acuity and perception
      of Purkinje's vessel shadows for prediction of the postoperative visual acuity
      after vitrectomy in diabetic vitreous hemorrhage].
AB  - BACKGROUND: In cases of strong vitreous hemorrhage due to diabetic vitreo
      retinopathy there is an uncertainty for the prediction of postoperative visual
      acuity after vitrectomy. This study compares the value of different preoperative
      measurements for the prognosis of postoperative visual acuity. METHOD AND
      PATIENTS: We evaluated retrospectively the reports of all patients who have been
      operated by vitrectomy due to diabetic vitreous hemorrhage at our hospital in
      2004 (first vitreoretinal surgery). The following measurements were evaluated:
      preoperative distance and reading VA, last known VA before hemorrhage, laser
      interference VA, Purkinje's vessel shadow and postoperative distance VA. RESULTS:
      42 patients had entire documentation of all evaluated parameters. The
      preoperative distance VA was 20/1000 (light perception to 20/60), only 3 patients
      had a reading VA. Laser interference VA was better than red light perception in
      13 patients (7 without red light perception). Purkinje's vessel shadows were
      positive in 22 patients, negative in 17 patients, but 3 patients did not
      understand the procedure. Prehemorrhage VA was known in 19 patients. Laser
      interference VA and last known VA prior to hemorrhage (in mean 20 months old) had
      the best correlation to postoperative VA (p > 0.05). Purkinje's vessel shadow
      predicts -- if positive -- a postoperative VA of 20/300 or better. CONCLUSIONS:
      Postoperative VA after vitrectomy due to diabetic vitreous hemorrhage is best
      predicted by prehemorrhage VA or laser interference VA, especially if no
      prehemorrhage VA is known. Positive Purkinje's vessel shadow predicts a
      postoperative VA of 20/300 or better.

PMID- 16639672
TI  - [Bilateral large conjunctival tumours as primary manifestation of sarcoidosis-
      successful treatment with steroid-depot-injections].
AB  - INTRODUCTION: Ocular manifestations of sarcoidosis vary enormously. They include
      the conjunctiva, lacrimal gland, orbita, intraocular structures and eye-lid,
      either isolated or combined. We describe a female patient who presented with
      unusually large, bilateral conjunctival tumours as a primary manifestation of
      sarcoidosis. PATIENT: A 79-year-old white woman was referred to us for further
      management of a persisting "conjunctivitis", which had been refractory to
      treatment with multiple medications. Initial examination disclosed swollen eye
      lids and bilateral large hard tumours of the inferior fornix. The obtained brush
      smear, which was cytopathologically evaluated, revealed epitheloid cells and
      multinucleate giant cells. After 4 weeks she developed three reddish-brown
      maculopapular lesions on her face. The subsequent biopsy from the left inferior
      fornix and the skin showed histopathologically a granulomatous epitheloid cell
      inflammation without central necrosis and without acid-proof bacilli. Therefore a
      sarcoidosis was included into the differential diagnosis. The systemic evaluation
      revealed no other manifestation. At first we tried to reduce the chronically
      inflammatory tumours with different immunomodulating local treatment forms. Only
      the repeated intralesional injection of a steroid depot showed a complete
      disappearance of all conjunctival and skin tumours. CONCLUSION: An isolated
      bilateral primary manifestation of sarcoidosis with large massive conjunctival
      tumours is very rare and clinically not typical. The non-invasive,
      cytopathological examination by means of brush smears offers a new perspective in
      the fast diagnosis of conjunctival manifestation of sarcoidosis. The tumours
      respond excellently to the intralesional injection of steroid depots.

PMID- 16639673
TI  - [Technique of vascular anastomosis: a look into its historical development].

PMID- 16639674
TI  - Bridge to operation with the GPIIb/IIIa inhibitor abciximab in high-risk coronary
      patients.
AB  - BACKGROUND: Glycoprotein-IIb/IIIa inhibitors are now frequently used in the
      cardiological treatment of high-risk coronary patients even if the patient is
      considered suitable for surgical intervention. However, there is no consensus
      whether GPIIb/IIIa inhibitors should be stopped before operation because of an
      increased risk of bleeding or if surgery should even be delayed until the
      anticoagulating effect subsides. METHODS: From June 2002 to August 2003 140
      patients who had to undergo primary aorto-coronary bypass for ongoing myocardial
      ischemia were enrolled in the present study. The patients received either
      clopidogrel, aspirin and heparin or additionally abciximab until operation.
      RESULTS: Although the intraoperative need for blood products was higher in the
      abciximab group, there was no significant difference in postoperative blood loss.
      The hemodynamic situation of the abciximab patients after the operation was
      better compared to the other groups. 30-day mortality was not increased when
      compared to the elective control group (6.7 % vs. 6.1 %). CONCLUSION: The
      GPIIb/IIIa inhibitor abciximab can be safely used as a bridge to operation and
      results in a better hemodynamic outcome in high-risk coronary patients while
      reducing the incidence of major ischemic events.

PMID- 16639675
TI  - Perioperative risk of aortic valve replacement after coronary artery bypass
      grafting.
AB  - OBJECTIVE: To evaluate the operative risk of aortic valve replacement (AVR) after
      coronary artery bypass grafting (CABG). METHODS: Twenty patients (sixteen male,
      four female) underwent AVR 1.5-20 years (mean: 8.2) after CABG. RESULTS: Patients
      had received a mean number of four bypass grafts (2-5) with the use of the left
      internal thoracic artery in seventeen patients. Mean age at the time of AVR was
      70.5 years (57-82). All patients suffered from an aortic stenosis with a mean
      orifice area of 0.74 cm (2) (0.34-1.1) and a mean pressure gradient of 52.4 mm Hg
      (22-78). Ten mechanical (mean diameter 23.6 mm, 21-27) and ten biological (22.1
      mm, 19-25) prostheses were implanted. Mean duration of surgery, cardiopulmonary
      bypass (CPB) and cross-clamp time were 322.1 (205-645), 169.2 (87-411), and 77.1
      (46-128) minutes, respectively. Fourteen patients had an uneventful postoperative
      course. A temporary neurological impairment, renal failure, and re-intubation for
      respiratory insufficiency for nine hours occurred in one patient each. Two
      patients died postoperatively (day 3 and 10) due to multiple cerebral
      infarctions. One patient required a replacement of the ascending aorta in deep
      hypothermia and re-implantation of the bypasses. He suffered from
      gastrointestinal bleeding on postoperative day 14 and expired on day 81 because
      of multi-organ failure. CONCLUSION: Aortic valve replacement after coronary
      artery bypass grafting is associated with an enhanced perioperative risk
      requiring meticulous decision-making and a sophisticated operative technique.

PMID- 16639676
TI  - Tirofiban (Aggrastat) protects platelets and decreases platelet-granulocyte
      binding in an extracorporeal circulation model.
AB  - OBJECTIVES: Extracorporeal circulation (ECC) induces platelet activation and
      inflammation with potentially life-threatening organ dysfunction. Short-acting GP
      IIb/IIIa inhibitors like tirofiban and eptifibatide protect platelets during ECC
      without increasing bleeding complications and may reduce inflammation. This study
      investigates anti-thrombotic and anti-inflammatory effects of different platelet
      inhibitors. METHODS: Control (untreated) and treated (using either 150 ng/mL
      tirofiban, 2.5 microg/mL eptifibatide, 0.7 microg/mL milrinone, 15 microg/mL
      dipyridamol, or 300 KIU/mL aprotinin) heparinized blood of healthy volunteers (n
      = 6) was recirculated in a well-established ECC model (Chandler loop). Percentage
      of platelet aggregates, P-selectin-expressing (activated) platelets, CD15
      positive aggregates (indicating proinflammatory platelet-granulocyte binding),
      and platelet counts were determined before (baseline) and after 30 minutes
      recirculation in unstimulated and ADP-stimulated samples using flow cytometry.
      Statistical analysis was performed using multifactor ANOVA after transforming the
      data (logarithms for counts and log odds for percentages). Least square means
      were backtransformed to obtain appropriate means and their 95 % confidence
      intervals. Multiple post-hoc comparisons were performed by Tukey's HSD test with
      a global alpha of 5 %. RESULTS: Significant inhibition was observed for: 1) ECC
      induced platelet aggregation by tirofiban (unstimulated: 2.2-fold/stimulated:
      2.46-fold), eptifibatide (unstimulated: 1.96-fold/stimulated: 2.65-fold), and
      milrinone (unstimulated: 1.87-fold/stimulated: 1.37-fold); 2) ECC-induced P
      selectin expression by tirofiban (unstimulated: 3.95-fold/stimulated: 2.54-fold),
      and eptifibatide (unstimulated: 5.87-fold/stimulated: 3.28-fold); 3) ECC-induced
      platelet loss by tirofiban (1.27-fold), and eptifibatide (1.25-fold); 4) ECC
      induced platelet-granulocyte binding by tirofiban (unstimulated: 2.25
      fold/stimulated: 1.59-fold), but not by eptifibatide. CONCLUSIONS: Amongst the
      investigated drugs only GP IIb/IIIa inhibitors decreased activation, aggregation,
      and loss of platelets during ECC but acted differently on platelet-granulocyte
      interaction. A short-acting GP IIb/IIIa inhibitor with the potential to inhibit
      platelet activation and platelet-leukocyte interaction should be considered both
      for platelet protection and inhibition of platelet-mediated inflammation during
      ECC.

PMID- 16639677
TI  - Does the additional use of heparin-coated extracorporeal circuits (ECC) optimize
      the effect of modified ultrafiltration (MUF) in pediatric perfusion?
AB  - BACKGROUND: Modified ultrafiltration (MUF) has been shown to exert beneficial
      effects on the coagulation system and the capillary leak after pediatric cardiac
      surgery using extracorporeal circulation (ECC). The aim of this study was to
      investigate whether the additional use of heparin-coated circuits is a useful
      option for improving biocompatibility. METHODS: We randomized 28 children, using
      heparin-coated ECC circuits in group A (n = 14) and an uncoated equivalent set in
      group B (n = 14). After congenital heart surgery, MUF was performed post ECC in a
      standardized fashion. Blood samples were analyzed preoperatively, 10 min, 30 min,
      1 h, and 48 h after ECC by flow cytometric analysis (FACSort) using surface
      antigens CD62/CD41b (platelets) and CD45/CD14 (monocytes). RESULTS: No
      significant difference was found with respect to mean age (20.6 months vs. 21.6
      months), mean body weight (9.2 kg vs. 8.4 kg), mean ultrafiltration rate (9.1
      ml/kg vs. 11.4 ml/kg), chest tube drainage, blood products, ICU stay, and 30-d
      survival. The percentage of CD62/CD41-positive platelets in group A (vs. B)
      increased up to 118 % at 60 min vs. 130 % ( P < 0.05) and declined to 98 % at 48
      h postop. vs. 99 % (n. s.). The percentage of CD45/CD14-positive monocytes in
      group A (vs. B) increased up to 158 % at 60 min vs. 155 % (n. s.) and declined to
      122 % (A) at 48 h postop. vs. 61 % (B) ( P > 0.05). CONCLUSIONS: Heparin coating
      of ECC in addition to MUF leads to a lower platelet activation. Monocyte surface
      markers CD45 and CD14 indicated a marked activation during ECC in both groups but
      additional heparin coating showed a better postoperative regeneration of monocyte
      markers in the late course indicating a beneficial additive effect.

PMID- 16639678
TI  - Impact of pressure recovery in the evaluation of the Omnicarbon tilting disc
      valve.
AB  - BACKGROUND: Pressure recovery is not taken into account when calculating trans
      prosthetic gradients after mechanical valve replacement using Doppler
      echocardiography. This may lead to underestimation of valvular performance.
      METHODS: Simultaneous measurement of Doppler and direct trans-prosthetic
      gradients was performed in a circulatory mock loop simulator with physiologic
      parameters at different heart rates and cardiac outputs for small-sized aortic
      Omnicarbon tilting disc valves (19 - 21 mm). RESULTS: In all adjustments the
      Doppler gradient significantly overestimated the net transvalvular gradient. The
      amount of pressure recovery averaged 59.3 %. CONCLUSIONS: Doppler
      echocardiography does not allow for pressure recovery, which is a significant
      phenomenon in the hemodynamic function of the Omnicarbon tilting disc valve.
      Valve performance is much better than expected from Doppler gradients.

PMID- 16639679
TI  - Clinically relevant tracheomalacia after repair of esophageal atresia: the role
      of minimal intra-operative dissection and timing for aortopexy.
AB  - BACKGROUND: Tracheomalacia is associated with esophageal atresia (EA), but may go
      unnoticed from external splinting forces. Intra-operative dissection with fistula
      division releases external splinting, revealing tracheomalacia only post
      operatively. Analysis of surgical technique may disclose an iatrogenic etiology.
      METHODS: From 1995 - 2004, 44 neonates underwent surgery for EA. All patients
      underwent pre-, intra- and postoperative bronchoscopy. Operative and
      bronchoscopic notes were studied for malacia, and extensive dissection of the
      esophagus and fistula from the trachea. RESULTS: Surgical mortality was 6.8 %.
      Pre-operative tracheomalacia was diagnosed in 3 patients, who eventually fared
      well. In 17 other patients, the pre-operative bronchoscopy was negative, but
      airway obstruction developed post-operatively. Tracheomalacia was documented at
      the site of the former fistula and surgical release maneuvers. Aortopexy was
      required in 5 instances, whereas 12 others with malacia were managed
      conservatively. CONCLUSIONS: Mediastinal connective tissue and the fistula may
      splint open the marginally diseased airway in patients with EA, the lack of which
      may disclose previously unknown tracheomalacia after repair. When aggressive
      release maneuvers have been required, early aortopexy may be preferred to
      ventilator dependency.

PMID- 16639680
TI  - Surgical treatment of primary soft tissue sarcomas involving the chest:
      experiences in 25 patients.
AB  - BACKGROUND: Primary soft tissue sarcomas of the chest wall are uncommon and data
      concerning treatment and results are sparse. We reviewed our experience with
      chest wall resections of these lesions. METHODS: Retrospective review of our
      database identified 25 patients (12 men, 13 women) who underwent chest wall
      resection for primary soft tissue sarcoma during the 18-year study period
      (January 1984 through to January 2002). The mean follow-up period was 46.5
      months. RESULTS: The 30-day mortality was zero. The cumulative 5-year survival
      rate of all 25 patients was 56.9 %, and the median survival 99.5 months. This
      compared with 42.2 % and a median survival of 36.0 months after chest wall
      resection for high grade tumor histology. Histological type grading clearly
      influenced long-term survival ( P = 0.036). Local recurrence occurred in 9
      patients, 6 of 8 who were resected with positive margins and 3 of 17 who were
      resected with negative margins. Chest wall resections extended with lung
      resections did not significantly impair postoperative pulmonary function compared
      to patients without concomitant lung resections. CONCLUSIONS: Chest wall
      resections in primary soft tissue sarcomas can be accomplished safely with a low
      mortality rate. Long-term survival can be achieved for primary soft tissue
      sarcomas but histological grading is of prognostic significance.

PMID- 16639681
TI  - Effect and duration of lung volume reduction surgery: mid-term results of the
      Brompton trial.
AB  - Although many studies have reported improvement in lung function following LVRS,
      the magnitude of improvement and subsequent decline has not been evaluated
      against medical therapy after the second year. METHODS: Existing pulmonary
      function records were collapsed for ech participant since randomisation from
      Brompton LVRS trial cohort. Longitudinal data analysis was used to profile th
      history of medically treated patients and the effect of LVRS. RESULTS: Pulmonary
      function results were collated from survivors over a median of 25 (17 to 39)
      months. The estimated immediate increase in mean FEV1, following surgery was
      +0.2591 (0.179, 0.339), with a rate of change of -0.0051 (-0.009, -0.001) per
      month compared to medical therapy (p < 0.001). The changes in the secondary
      outcome measures (LVRS compared to medical therapy) were an increase in FVC (p =
      0.004), decrease in RV (p < 0.001) and TLC (p < 0.001), with differences that
      were maintained over time. The initial reduction in RV/TLC ration was sustained
      (p < 0.001), but the estimated initial increase in peak flow was accompanied by a
      gradual decline that was not statistically significant (p = 0.062). KCOc showed
      no immediate change, but there was a gradual sustained increase with time (p =
      0.009). Mean oxygen saturations improved and continued to do so compared to
      patients on medical therapy (p = 0.001). CONCLUSIONS: The immediate increase in
      FEV1 is not sustained, although the mechanical improvements of LVRS on increasing
      FVC, reducing both the RV and RV/TLC ratio, appear to be maintained. The
      important benefits of LVRS may be the gradual and sustained increase in transfer
      factor accompanied by improved oxygen saturations.

PMID- 16639682
TI  - Detecting the limits of bronchial closure methods in an animal model.
AB  - BACKGROUND: Bronchopleural fistula is a serious complication of major lung
      resections that may lead to mortality. An experimental animal model was designed
      to find out the safest bronchial closure method by comparing leakage rates under
      pressure. METHODS: The tracheobronchial trees of 50 freshly dead sheep were
      prepared for either manual closure or closure with a stapler. After left
      pneumonectomy, the specimens were divided into five groups (n = 10); 3/0
      Premilene suture was used with two "u" sutures + interrupted sutures in Group I;
      in Group II, 3/0 Premilene sutures with continuous horizontal mattress + over
      over continuous sutures were used. In Group III and IV the same techniques were
      used with 3/0 Vicryl. A stapler was used in Group V. Specimens were intubated
      with an endotracheal tube, connected to a sphygmomanometer, and subsequently
      positioned under water. The pressure level at which we detected air bubbles
      indicated the limits of the technique. RESULTS: The median leakage pressure
      resistance was significantly lower in Group III (135 mm Hg) ( P = 0.001). The
      best results were achieved by using the continuous horizontal mattress + over
      over continuous suture technique. No statistical significance difference was
      found between the stapler group, Groups I, II, and IV in terms of median leakage
      pressures. CONCLUSIONS: This trial suggests that manual suture closure using an
      appropriate technique and monofilament materials is as safe as the stapler.

PMID- 16639683
TI  - Clinical value of mediastinoscopy in the diagnosis of sarcoidosis: an analysis of
      68 cases.
AB  - Mediastinoscopy was performed for confirmation of the diagnosis in 68 patients
      who were suspected clinically and radiologically of having sarcoidosis. In 66 of
      68 cases in which mediastioscopy was performed a diagnosis was attained. In 35
      cases, endobronchial biopsy was performed by bronchoscopy. In only 5 of these
      (14.2 %) was the diagnosis of sarcoidosis confirmed. The sensitivity of
      mediastinoscopy was remarkably superior compared with that of endobronchial
      biopsy. No complication developed with either mediastinoscopy or endobronchial
      biopsy. In Turkey, mediastinoscopy without any complication costs about 650 USD
      while bronchoscopy and endobronchial biopsy cost about 150 USD. In our study in
      which we looked for a histological confirmation -- in the cases suspected of
      sarcoidosis -- mainly through mediastinoscopy and rarely through other methods
      (i.e., endobronchial biopsy in one case, skin biopsy in another), we did not come
      up with a different diagnosis. Therefore, patients suspected of having
      sarcoidosis should undergo a careful clinical, laboratory, and radiologic
      examination; they should be under continuous close observation; when necessary
      (e.g., skin and lip biopsy), the tissue diagnosis should be made by other
      methods, but if there is the possibility of a disease such as tuberculosis and
      lymphoma, mediastinoscopy should be performed. The diagnosis of stage 3
      sarcoidosis is difficult. For diagnosis, sometimes videothoracoscopy or
      explorative thoracotomy may be necessary. However, in all our 3 cases with stage
      3, we reached the diagnosis of sarcoidosis by the less invasive and less
      expensive method of mediastinoscopy. Despite our small number of cases, we
      believe that mediastinoscopy is a very important instrument for diagnosis of
      stage 3 sarcoidosis.

PMID- 16639684
TI  - A completely thoracoscopic lobectomy/segmentectomy for primary lung cancer-
      technique, feasibility, and advantages.
AB  - INTRODUCTION: A completely thoracoscopic lobectomy/segmentectomy for primary lung
      cancer was designed to maximize the benefits of this type of minimally invasive
      surgery. The technique, feasibility, and advantages of this surgical modality
      over the conventional procedure were investigated. MATERIALS AND METHODS: Between
      January 2003 and December 2004, 38 patients underwent a lobectomy (n = 30) or
      segmentectomy (n = 8) for clinical stage IA primary lung cancer. A resection
      using a standard thoracotomy (Thoracotomy Group) was performed in 19 patients,
      and a completely thoracoscopic resection was performed in 10 cases (CTR Group).
      Conventional video-assisted thoracic surgery with a mini-thoracotomy was
      performed in 9 cases. RESULTS: All CTR lobectomies or segmentectomies were
      carried out safely without any major complications. The number of resected
      mediastinal lymph nodes was similar in both groups. There was a tendency for the
      hospital stay to be somewhat shorter in the CTR Group. With respect to
      postoperative pain as evaluated by a visual analogue scale (VAS), the CTR Group
      showed a significantly lower level of pain in comparison to the Thoracotomy Group
      ( P = 0.024 on day 2). CONCLUSIONS: We concluded that a complete thoracoscopic
      lung resection is a safe and technically feasible surgical procedure which
      enables us to make thoracoscopic lung resections less invasive.

PMID- 16639685
TI  - Endoscopic radial artery harvesting through a single incision.
AB  - A method of radial artery harvesting through a single 3-cm skin incision is
      presented. This technique is performed with an endoscope inserted into a
      retractor and a harmonic scalpel for dissection of the artery. Transsection of
      the artery is carried out with a pre-tied endoloop. The endoscopic harvesting can
      be done in 45 minutes, resulting in less operative trauma and an excellent
      cosmetic outcome.

PMID- 16639686
TI  - Heart transplantation after Fontan's procedure with bilateral cavopulmonary
      connections.
AB  - We present a young female patient with three caval drainages after complete
      Fontan's procedure and with bilateral bidirectional cavopulmonary connections who
      underwent orthotopic heart transplantation. Instead of reconstructing the
      hypoplastic innominate vein the persistent left superior caval vein was
      reanastomosed via the recipient's coronary sinus into the right atrium.

PMID- 16639687
TI  - Cardiac surgery in a patient with haemophilia A.
AB  - In this report we describe the successful cardiac surgery in a patient with
      haemophilia A. To undergo to triple on-pump coronary artery bypass grafting the
      level of factor VIII was estimated to be 100 %, during the operation and the
      first postoperative week. To reach this level, bolus therapy with B-domain
      deleted recombinant factor VIII was administered in a low substitution scheme.
      There was no bleeding complication. The patient discharged on the 14th
      postoperative day.

PMID- 16639688
TI  - Mechanical circulatory support for profound cardiac circulatory shock status due
      to postoperative pulmonary artery bleeding.
AB  - A 77-year-old patient suffering from life-threatening pulmonary artery bleeding
      after pulmonary lobectomy was resuscitated but had refractory cardiogenic shock
      after the bleeding was controlled. We used mechanical circulatory support with
      extracorporeal membrane oxygenation and intra-aortic balloon pump to overcome the
      hemorrhagic shock-related cardiac suppression and multi-organ injury in the post
      resuscitation critical period.

PMID- 16639689
TI  - Mucinous cystadenocarcinoma--an extremely rare tumor in a young patient.
AB  - We report on an extremely rare case of pulmonary mucinous cystadenocarcinoma. A
      29-year-old male patient was admitted because of progressive enlargement of a
      right lower lobe mass over a period of 10 years. Right lower lobectomy was
      performed after a malignant mucinous cystadenocarcinoma was diagnosed by
      intraoperative frozen section. PET and CT scans did not detect metastatic
      disease. This case is the youngest patient reported so far with a malignant
      pulmonary mucinous cystadenocarcinoma and highlights the importance of close
      follow-up of indeterminate pulmonary nodules in patients with unremarkable
      history.

PMID- 16639690
TI  - The sulfone syndrome secondary to dapsone prophylaxis in a patient undergoing
      unrelated hematopoietic stem cell transplantation.
AB  - Dapsone is commonly used for pneumocystis carinii pneumonia (PCP) prophylaxis in
      immunocompromised patients. It has been used as an alternative therapy in the
      hematopoietic stem cell transplant (HSCT) setting in patients who can't tolerate
      trimethoprim-sulfamethoxazole. The Sulfone syndrome is not a well-known sequela
      of dapsone therapy and occurs at various doses, ranging from 50-300 mg/d. In all
      cases the syndrome occurs within 2 months of initiating therapy. Its clinical
      manifestations include: fever, methemoglobinemia, hemolytic anemia, exfoliative
      dermatitis and transaminits. A 51-year old female underwent a matched unrelated
      hematopoiectic stem cell transplant for acute mylogenous leukemia. Dapsone
      therapy was initiated on day +28 at a dose of 100 mg/day for PCP prophylaxis
      secondary to the patient's history of a sulfonamide allergy. On day +59, one
      month after initiation of therapy she developed hepatitis, hemolytic anemia,
      fever and methemoglobinemia of 8%. She was transferred to the intensive care unit
      and subsequently developed an exfoliative dermatitis. We conclude that the
      clinical presentation of this patient after HSCT on dapsone therapy coincide with
      the sulfone syndrome not previously described in a patients after HSCT.

PMID- 16639691
TI  - Nuchal translucency in dichorionic twins conceived after assisted reproduction.
AB  - OBJECTIVES: As opposed to biochemical markers of Down syndrome, nuchal
      translucency (NT) was once thought to be a more reliable screening marker for
      high order multiple pregnancies and pregnancies conceived after assisted
      conception. Recent data suggested that NT in singleton fetuses from assisted
      reproduction technology (ART) was thicker than those from singleton pregnancies.
      The present study compared the thickness of NT in dichorionic twins from natural
      conception and assisted reproduction. METHODS: A retrospective analysis for
      comparison of NT thickness on 3319 spontaneous singletons, 19 pairs of
      spontaneous twins and 27 pairs of assisted reproduction twins was performed.
      RESULTS: The median NT multiple of median (MoM) of spontaneous singletons was
      1.00. For twins, the median NT MoM for pregnancies after assisted reproduction
      and natural conception were 1.02 and 1.07 respectively. There was no statistical
      difference in the NT thickness among the three pregnancy groups. CONCLUSION:
      Contrary to the observed increase in NT in singleton pregnancies from assisted
      reproduction, the NT in dichorionic twins was comparable to the spontaneous ones.
      The mode of conception appears to impose differential influence on singletons and
      twins.

PMID- 16639692
TI  - Differential expression of glucocorticoid receptor in human breast tissues and
      related neoplasms.
AB  - Glucocorticoid receptor (GR) is a steroid hormone receptor that has been shown to
      play important roles in mammary development and differentiation, and has been
      implicated in breast tumourigenesis, but its precise biological significance in
      mammary pathophysiology remains unclear. In order to generate a comprehensive
      expression profile for GR in normal versus neoplastic breast tissues, GR
      expression was investigated in situ in 400 human breast tissue samples,
      comprising normal tissue and a range of benign, pre-invasive, and invasive
      lesions, using immunohistochemical assays. The novel expression of GR in
      myoepithelium, not observed in luminal epithelium, not only demonstrates
      expression patterns exclusive to the alpha form of oestrogen receptor and
      progesterone receptor and suggests distinctive functions between GR and these two
      important steroid hormone receptors in the breast, but may also indicate unique
      physiological and perhaps pathological roles for the myoepithelium in mediating
      the effects of glucocorticoid hormones in the breast. The strong expression of GR
      in metaplastic carcinomas (94.4%) and malignant phyllodes tumours (92.3%)
      suggests a pathogenetic role for GR, and implies that targeting GR in these
      tumours may have potential therapeutic application. However, studies on the roles
      of GR in mammary carcinogenesis should be interpreted with great caution, based
      on the lack of GR expression in cancer cells in the great majority (98.2%) of non
      metaplastic carcinomas, which has gone unnoticed in previous studies. This marked
      discrepancy warrants a re-examination of the biological roles of GR in the
      pathophysiology of breast malignancy. The lack of methylation in the promoter
      region of the GR gene in all 118 non-metaplastic carcinomas, as demonstrated by
      methylation-specific PCR and bisulphite DNA sequencing analysis, indicates that
      methylation is less likely to play a role in the reduction of GR expression in
      non-metaplastic carcinoma of the breast.

PMID- 16639693
TI  - Prognostic significance of PU.1 in follicular lymphoma.
AB  - Very few prognostic factors are known in follicular lymphoma (FL), a common
      malignancy of germinal centre (GC) B-cells. The Follicular Lymphoma International
      Prognostic Index (FLIPI) thus far appears to be the most important predictor of
      clinical outcome. This study explores the predictive power of the degree of GC
      differentiation for outcome in FL. Samples from 73 patients with FL were
      evaluated by immunohistochemistry for expression of GC markers. Strong PU.1,
      CD20, and CD75 expression were significantly associated with longer progression
      free survival (PFS) and overall survival (OS). Results for PFS were independent
      of the International Prognostic Index or the Italian Lymphoma Intergroup
      prognostic index for CD75 and PU.1, but only PU.1 expression was independent of
      FLIPI for PFS and OS. Oct-2 was weakly expressed overall, but more strongly in
      higher grades of FL; it had a trend for negative linear association with PU.1 and
      strong positive linear association with CD27, which possibly reflects its role in
      terminal B-cell differentiation. We show that the level of GC differentiation, as
      determined by the levels of PU.1, CD75, CD20, Bcl-6, and CD10 expression, has an
      association with outcome in patients with FL. While this is determined
      qualitatively in most studies of diffuse large B-cell lymphoma, in FL there is a
      quantitative positive association between a high level of expression of GC
      antigens and longer OS and PFS even when data are stratified by the FLIPI score.

PMID- 16639695
TI  - Re: Jarrett. Viruses and lymphoma/leukaemia. J Pathol 2006;208:176-186.

PMID- 16639696
TI  - Evidence for the early onset of aberrant promoter methylation in urothelial
      carcinoma.
AB  - There is evidence that carcinoma in situ (CIS) is the precursor of invasive
      urothelial carcinoma, a tumour characterized by frequent gene promoter
      methylation. The timing of altered DNA methylation is unknown in this pathway.
      Here we investigate gene methylation in 196 consecutive samples of normal
      urothelium, CIS, and tumours from 104 patients with both CIS and invasive
      urothelial carcinoma using quantitative methyl-sensitive polymerase chain
      reaction for six genes (p16, p14, E-cadherin, RARbeta2, RASSF1a, and GSTP1).
      Control normal urothelial samples from 15 patients with no history of urothelial
      carcinoma were also analysed. Immunohistochemistry established the expression of
      well-characterized CIS markers p53 and cytokeratin 20. Promoter methylation
      occurred frequently in both normal urothelium and CIS samples from patients with
      urothelial carcinoma, and increased with progression from normal to invasive
      urothelial carcinoma, at both specific loci (chi2 test: E-cadherin, p=0.0001;
      RASSF1a, p=0.003, RARbeta2, p=0.007, p16, p=0.024) and in general (methylation
      indices [t-test, p<0.0001]). Methylation was associated with cytokeratin 20
      expression (t-test, p=0.004) and poor prognosis, and with increased progression
      to tumour death in patients whose CIS samples showed methylation, in comparison
      with those without methylation (log rank p<0.03). Promoter methylation occurs
      early in the urothelial carcinogenic pathway and appears to be a good biomarker
      of the invasive urothelial carcinoma phenotype.

PMID- 16639697
TI  - PTOV1: a novel testosterone-induced atherogenic gene in human aorta.
AB  - There are gender differences in the development of atherosclerosis, possibly
      owing to differences in sex steroid hormone action and/or metabolism. One of the
      atherogenic effects of testosterone is thought to be androgen receptor (AR)
      mediated vascular smooth muscle cell (VSMC) proliferation. However, the detailed
      mechanism of this effect, particularly the identity of the genes associated with
      VSMC proliferation, remains largely unknown. Therefore, we first employed
      microarray analysis and, subsequently, quantitative RT-PCR to analyse RNA
      expression in AR-positive human VSMCs treated with testosterone in order to
      detect testosterone-induced genes associated with cell proliferation. We further
      examined whether the genes identified were involved in cell proliferation using
      small interfering RNA (siRNA) transfection. Expression of the gene products was
      then evaluated in human aorta with various degrees of atherosclerosis in order to
      evaluate the clinical relevance of the findings. Both microarray and quantitative
      RT-PCR analyses demonstrated marked induction of the human prostate overexpressed
      protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently
      identified as a novel androgen-induced gene involved in prostate tumour cell
      proliferation. Inhibition of PTOV1 by transfection of its corresponding siRNA
      suppressed testosterone-induced cell proliferation. In human aorta, PTOV1
      immunoreactivity in the nuclei of neointimal VSMCs was abundantly detected in
      male aorta with mild atherosclerotic changes compared with female aorta or male
      aorta with severe atherosclerotic changes. These findings indicate that the PTOV1
      gene is androgen-responsive in VSMCs and that it may play an important role in
      androgen-related atherogenesis in the human aorta, particularly early
      atherosclerosis in the male aorta, through regulating proliferation of neointimal
      VSMCs.

PMID- 16639698
TI  - Variable expression of Epstein-Barr virus-induced gene 3 during normal B-cell
      differentiation and among B-cell lymphomas.
AB  - Epstein-Barr virus (EBV)-induced gene 3 (EBI3) is expressed by tumour cells in
      several EBV-associated malignancies. EBI3 was recently found to associate with a
      novel peptide, p28, to form a new heterodimeric cytokine, called interleukin-27.
      In this study, we investigated EBI3 and p28 expression in normal human B
      lymphocytes and in non-EBV-associated B-cell lymphomas. Low levels of EBI3 were
      detected in purified tonsillar B cells and expression was upregulated upon anti
      CD40 or anti-micro stimulation via NF-kappaB activation. In non-neoplastic
      tissues, EBI3 expression by lymphocytes was largely restricted to a subset of
      germinal centre (GC) B cells located at the margin of the light zone, in close
      contact with CD3+ T lymphocytes. Over 50% of EBI3+ GC B cells were engaged in
      cell proliferation as assessed by Ki67 expression, and 10-30% expressed MUM1, an
      early marker of plasma cell differentiation expressed by late centrocytes. Many
      EBI3+ GC B cells had downregulated bcl-6 expression, which further suggests that
      these cells correspond to late CD40-activated centrocytes. Immunohistochemical
      analysis of 64 B-cell lymphomas showed that the highest EBI3 levels were detected
      in follicular lymphomas and in diffuse large B-cell lymphomas of both GC B-cell
      like or non-GC B-cell-like types. No or rare p28 expression was detected in
      normal or tumour B cells. This constitutive expression of EBI3 by neoplastic B
      cells may be involved in lymphomagenesis, and may be a useful marker for lymphoma
      diagnosis.

PMID- 16639699
TI  - Ab initio potential energy surface and predicted microwave spectra for Ar--OCS
      dimer and structures of Arn--OCS (n = 2-14) clusters.
AB  - An ab initio potential energy surface for the Ar--OCS dimer was calculated using
      the coupled-cluster singles and doubles with noniterative inclusion of connected
      triples [CCSD(T)] with a large basis set containing bond functions. The
      interaction energies were obtained by the supermolecular approach with the full
      counterpoise correction for the basis set superposition error. The CCSD(T)
      potential was found to have two minima corresponding to the T-shaped and the
      collinear Ar--SCO structures. The two-dimensional discrete variable
      representation method was employed to calculate the rovibrational energy levels
      for five isotopomers Ar--OCS, Ar--OC34S, Ar--O13CS, Ar--18OCS, and Ar--17OCS. The
      calculated pure rotational transition frequencies for the vibrational ground
      state of the five isotopomers are in good agreement with the observed values. The
      corresponding microwave spectra show that the b-type transitions (Delta Ka = +/
      1) are significantly stronger than the a-type transitions (Delta Ka = 0). Minimum
      energy structures of the Ar2--OCS trimer were been determined with MP2
      optimization, whereas the minimum-energy structures of the Arn--OCS clusters with
      n = 3-14 were obtained with the pairwise additive potentials. It was found that
      there are two minima corresponding to one distorted tetrahedral structure and one
      planar structure for the ternary complex. The 14 nearest neighbor Ar atoms form
      the first solvation shell around the OCS molecule.

PMID- 16639700
TI  - T-cell epitopes of the La/SSB autoantigen: prediction based on the homology
      modeling of HLA-DQ2/DQ7 with the insulin-B peptide/HLA-DQ8 complex.
AB  - T-cell epitopes are important components of the inappropriate response of the
      immune system to self-proteins in autoimmune diseases. In this study, the
      candidate T-cell epitopes of the La/SSB autoantigen, the main target of the
      autoimmune response in patients with Sjogren's Syndrome (SS), and Systemic Lupus
      Erythematosus (SLE) were predicted using as a template the HLA-DQ2 and DQ7
      molecules, which are genetically linked to patients with SS and SLE. Modeling of
      DQ2 and DQ7 was based on the crystal structure of HLA-DQ8, an HLA molecule of
      high risk factor of type I diabetes, which is also an autoimmune disease. The
      quality and reliability of the modeled DQ2 and DQ7 was confirmed by the
      Ramachandran plot and the TINKER molecular modeling software. Common and/or
      similar candidate T-cell epitopes, obtained by comparing three different
      approaches the Taylor's sequence pattern, the TEPITOPE quantitative matrices, and
      the MULTIPRED artificial neural network, were subjected to homology modeling with
      the crystal structure of the insulin-B peptide complexed with HLA-DQ8, and the
      best superposed candidate epitopes were placed into the modeled HLA-DQ2 and DQ7
      binding grooves to perform energy minimization calculations. Six T-cell epitopes
      were predicted for HLA-DQ7 and nine for HLA-DQ2 covering parts of the amino
      terminal and the central regions of the La/SSB autoantigen. Residues
      corresponding to the P1, P4, and P9 pockets of the HLA-DQ2 and DQ7 binding
      grooves experience very low SASA because they are less exposed to the
      microenvironment of the groove. The proposed T-cell epitopes complexed with HLA
      DQ2/DQ7 were further evaluated for their binding efficiency according to their
      potential interaction energy, binding affinity, and IC50 values. Our approach
      constitutes the ground work for a rapid and reliable experimentation concerning
      the T-cell epitope mapping of autoantigens, and could lead to the development of
      T-cell inhibitors as immunotherapeutics in autoimmune diseases.

PMID- 16639701
TI  - An agent-based system to discover protein-protein interactions, identify protein
      complexes and proteins with multiple peptide mass fingerprints.
AB  - Proteins "work together" by actually binding to form multicomponent complexes
      that carry out specific functions. Proteomic analyses based on the mass spectrum
      are now key methods to determine the components in protein complexes. The protein
      protein interaction or functional association may be known to exist among the
      extracted protein spots while analyzing the proteins on the 2D gel. In this
      study, we develop an agent-based system, namely AgentMultiProtIdent, which
      integrated two protein identification tools and a variety of databases storing
      relations among proteins and used to discover protein-protein interactions and
      protein functional associations, and identify protein complexes and proteins with
      multiple peptide mass fingerprints as input. The system takes Multiple Peptide
      Mass Fingerprints (PMFs) as a whole in the protein complex or protein
      identification. With the relations among proteins, it may greatly improve the
      accuracy of identification of protein complexes. Also, possible relationship of
      the multiple peptide mass fingerprints, such as ontology relation, can be
      discovered by our system, especially in the identification of protein complexes.
      The agent-based system is now available on the Web at
      http://dbms104.csie.ncu.edu.tw/ approximately protein/NEW2/.

PMID- 16639702
TI  - The regulation of glucose transporter (GLUT1) expression by the RNA binding
      protein HuR.
AB  - HuR is a ligand for nuclear mRNAs containing adenylate-uridylate-rich (ARE)
      elements in the 3'-untranslated region. Once bound to the mRNA, HuR is recognized
      by adapter proteins that then facilitate nuclear export of the complex. In the
      cytosol, HuR is thought to function to control stability and translation of its
      ligand message. We have previously demonstrated that HuR is constitutively
      expressed in the 3T3-L1 cells and shuttles from the nucleus to the cytosol, but
      remains predominantly nuclear in the preadipocytes and that as the cells
      differentiate, there is a marked increase in the proportion of HuR in the cytosol
      at any time. The GLUT1 glucose transporter is also expressed in both
      preadipocytes and adipocytes and in vitro RNA gel shifts indicate the mRNA is a
      ligand for HuR. However, HuR complexes containing the GLUT1 mRNA can only be
      isolated from the terminally differentiated adipocytes. Moreover, position
      analysis of the GLUT1 mRNA and HuR protein in polysome profiles demonstrates a
      shift to the most dense region of the gradient for both message and protein with
      adipocyte differentiation. Consistent with a regulatory role in the control of
      GLUT1 expression, siRNA-mediated decrease in HuR protein resulted in a decreased
      expression of GLUT1 protein. These data suggest that HuR contributes to the
      metabolic function of the adipocyte through mediation of post-transcriptional
      regulatory events.

PMID- 16639703
TI  - Characterization of the methanolic extract of hops using capillary
      electrophoresis-electrospray ionization-mass spectrometry.
AB  - Hops are used almost exclusively for bitterness and flavor by brewers. We propose
      the first analytical application of CZE coupled to ESI-MS for the separation and
      structural elucidation of organic compounds in the methanolic extracts of hops,
      and different extraction procedures of the plant material have been carried out.
      The proposed method permits the identification of hop polyphenols (flavonoids
      glycosides and chalcones), bitter acids (alpha-acids and beta-acids), and their
      oxidation products. The optimization of CZE parameters (pH, concentration, and
      type of buffer) and ESI-MS parameters (nature and flow rate of the sheath liquid,
      nebulizer pressure, drying gas flow rate, temperature, and compound stability)
      have permitted the development of a rapid, simple, direct, and straightforward
      CZE-ESI-MS method for the identification of components of methanolic extracts
      from different hops used in the brewing process.

PMID- 16639704
TI  - Single potential electrophoresis microchip with reduced bias using pressure pulse
      injection.
AB  - We propose two variants of a new injection technique for use in electrophoresis
      microchips, called "front gate pressure injection" and "back gate pressure
      injection", that both enable a controlled and reproducible sample introduction
      with reduced bias compared to electrokinetic gated injection. A continuous flow
      of a test solution of fluorescein/rhodamine B in 20 mM Tris/boric acid buffer (pH
      8.6) sample test solution is electrokinetically driven near to the entrance of
      the separation channel, using a single voltage (3 kV) that is constant in time. A
      sample plug is injected in the separation channel by a pressure pulse of the
      order of 0.1 s. The latter is generated using the mechanical deflection of a PDMS
      membrane that is loosely placed on a dedicated chip reservoir. The analysis of
      the peak area ratio of the separated compounds demonstrates a nearly constant
      sample composition when using pressure-based injection. A small remaining
      injection bias for the shortest membrane deflection times can be attributed to a
      dilution effect of the charged compound due to the presence of an electrical
      field transverse to the sample flow boundary in the channel junction.

PMID- 16639706
TI  - Is long-term humoral immunity in the mucosa provided by long-lived plasma cells?
      A question still open.
AB  - The biology of antibody-secreting cells is still a matter of controversial
      discussion. One of the key questions is how the migration and lifespan of
      antibody-secreting cells is linked to their generation. A paper in this issue of
      the European Journal of Immunology provides further information on the generation
      of long-term mucosal immune responses; however, the study leaves many questions
      unanswered as discussed in this brief Commentary.

PMID- 16639707
TI  - Optimizing cancer immunotherapy trials: back to basics.
AB  - Attempts to raise effective immunity against cancer are benefiting from
      information on the nature of the immunity involved and its regulation and,
      perhaps, now it is time to step back and define our approach in molecular terms
      prior to clinical testing. Although there are immunological differences between
      mice and patients, results from murine studies are encouraging early
      'translation' of concepts to the clinic and it is vital to take immunological
      principles emerging from mice into clinical vaccine design. One is the
      requirement to break tolerance against over-expressed self-antigens, a
      potentially risky procedure but necessary for several cancer targets. A study in
      this issue of the European Journal of Immunology attempts to do this by using
      xenogeneic antigens, albeit with variable outcome. The unstated goal is to
      activate T-cell help but this can be achieved more effectively by harnessing a
      predictable anti-microbial repertoire. The second issue lies in the delivery of
      antigen. One strategy is "prime/boost" using DNA priming and boosting with a
      viral vector; however, this induces blocking immunity against viral proteins, and
      must be used judiciously. There are other physical methods to increase immunity
      such as electroporation, which can itself be used in 'prime/boost' sequence.
      These twin problems of engagement of T-cell help and delivery of adequate antigen
      can now be addressed by applying immunological logic to cancer vaccines.

PMID- 16639708
TI  - Surface antibacterial characteristics of plasma-modified polyethylene.
AB  - The antibacterial characteristics of triclosan- or bronopol-coated and plasma
      modified polyethylene (PE) are investigated. The modified PE samples exhibit
      excellent bactericidal effects against Escherichia coli and Staphylococcus aureus
      even when the bacteria concentration in the suspension is 10(6) colony forming
      units (CFU)/mL. However, when the concentration exceeds 10(8) CFU/mL, the
      materials fail to develop noticeable resistance to large amount of bacteria
      because of the formation of a bacterial biofilm on their surfaces. The PE treated
      by this relatively simple technique possesses excellent antimicrobial properties
      and is useful in biomedical and disinfection applications because the bacteria
      concentrations in most situations are well below 10(6) CFU/mL.

PMID- 16639710
TI  - Regulation of osteoclastogenesis by gap junction communication.
AB  - Receptor activator of NF-kappaB ligand (RANKL) is crucial in osteoclastogenesis
      but signaling events involved in osteoclast differentiation are far from complete
      and other signals may play a role in osteoclastogenesis. A more direct pathway
      for cellular crosstalk is provided by gap junction intercellular channel, which
      allows adjacent cells to exchange second messengers, ions, and cellular
      metabolites. Here we have investigated the role of gap junction communication in
      osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the
      gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells
      and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction
      communication as demonstrated by a scrape loading Lucifer Yellow dye transfer
      technique. CBX caused a dose-dependent inhibition (significant > or = 90 microM)
      of the number of tartrate-resistant acid phosphatase (TRAP)-positive
      multinucleated cells formed in 7- to 8-day marrow cultures stimulated by
      parathyroid hormone (PTH; 10 nM) or forskolin (FSK; 1 microM). Furthermore, CBX
      (100 microM) significantly inhibited prostaglandin E2 (PGE2; 10 microM) and
      1,25(OH)2-vitamin D3 stimulated osteoclast differentiation in the mouse bone
      marrow cultures. Consequently, quantitative real-time polymerase chain reaction
      (PCR) analysis demonstrated that CBX downregulated the expression of osteoclast
      phenotypic markers, but without having any significant effects on RANK, RANKL,
      and osteoprotegerin (OPG) mRNA expression. However, the results demonstrated that
      CBX significantly inhibits RANKL-stimulated (100 ng/ml) osteoclastogenesis in the
      mouse bone marrow cultures. Taken together, our results suggests that gap
      junctional diffusion of messenger molecules interacts with signaling pathways
      downstream RANKL in osteoclast differentiation. Further studies are required to
      define the precise mechanisms and molecular targets involved.

PMID- 16639711
TI  - The long-term but not the short-term antiviral effect of IFN-alpha depends on
      Flt3 ligand and pDC.
AB  - The cooperation between IFN-alpha/beta and FL, the ligand of Fms-like tyrosine
      kinase 3 (Flt3), plays an important role in the defense against herpes simplex
      virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFN
      alpha has a short-term, FL-independent and a long-term, FL-dependent protective
      effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is
      very low and DC numbers in the spleen are reduced. The treatment of these mice
      with rIFN-alpha at day 6 resulted in an increased resistance against infection
      with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-alpha at birth induced
      both FL and plasmacytoid DC (pDC), resulting in enhanced resistance against HSV-1
      at day 7. In contrast, in mice lacking FL, IFN-alpha treatment at birth did not
      influence the splenic cell composition and had no effect on viral protection. The
      transfer of pDC to mice lacking FL enhanced viral resistance. Therefore, the
      induction and function of pDC, normally controlled by IFN-alpha/beta and FL, are
      decisive for viral resistance in neonatal mice.

PMID- 16639713
TI  - Expression analysis of LacZ gene placed in the locus of Cnot7 exhibits its
      activity in osteoblasts in vivo and in mineralized nodules in vitro.
AB  - CCR4-NOT complex 7 (Cnot7) was identified as a regulator of gene expression in
      yeast and evolutionally conserved in mammals. Cnot7 deficient male mice exhibit
      abnormality in spermatogenesis. As these mice contained construct to express
      LacZ, we followed the expression patterning in these animals. LacZ was expressed
      in osteoblasts located in the primary spongiosa in adult mice. Cellular analysis
      indicated that LacZ is expressed in osteoblasts but not in osteoclasts. In the
      mineralized nodules formed in the culture of bone marrow cells obtained from
      Cnot7 +/- mice, LacZ expression was mainly observed in the cells forming
      mineralized nodules but not in un-mineralized area scattered around the periphery
      of the nodules. LacZ blue positive cells were gradually depositing minerals along
      its time course of the in vitro mineralization assay. Cnot7 expression was
      enhanced by the treatment with BMP. These data suggest that Cnot7 is expressed in
      osteoblasts and is associated with mineralization.

PMID- 16639714
TI  - ARC protects rat cardiomyocytes against oxidative stress through inhibition of
      caspase-2 mediated mitochondrial pathway.
AB  - Apoptosis repressor with a CARD domain (ARC) has been demonstrated to protect
      heart cells against ischemia/reperfusion (I/R) injury. In this study, we
      investigated the mechanism by which ARC protects heart cells against oxidative
      stress. We monitored the extent of apoptosis and activity of multiple components
      of the intrinsic apoptotic pathway in rat cardiac myoblast cell line H9c2 with
      either reduced or increased expression of ARC during oxidative stress.
      Overexpression of ARC-inhibited oxidative stress-induced caspase-2/3 activation,
      cytochrome c release, and translocation of Bax to mitochondria. Furthermore,
      phosphorylation of ARC at threonine 149 was found to be critical to its function.
      ARC containing a T149A mutation failed to translocate to mitochondria, did not
      inhibit caspase-2 activation, and had a dominant negative effect against the
      protective effect of endogenous ARC during oxidative stress. In addition, wild
      type ARC but not the T149A mutant inhibited cell death induced by overexpression
      of caspase-2. Using a yeast two-hybrid (YTH) screening approach and co
      immunoprecipitation (Co-IP), we found that protein phosphatase 2C (PP2C)
      interacted with ARC and that PP2C mediated-dephosphorylation of ARC inhibited its
      anti-apoptotic activity. Eliminating either the N-terminal CARD domain or the C
      terminal P/E domain also abolished the anti-apoptotic function of ARC, suggesting
      that full-length ARC is required for its apoptotic inhibition. These results
      indicate that ARC plays an important role in protection of H9c2 cells against
      oxidative stress-induced apoptosis by phosphorylation-dependent suppression of
      the mitochondria-mediated intrinsic pathway, partially initiated through the
      activation of caspase-2.

PMID- 16639715
TI  - Interaction of IGF signaling and the androgen receptor in prostate cancer
      progression.
AB  - The insulin-like growth factor type I receptor (IGF-IR) has been suggested to
      play an important role in prostate cancer progression and possibly in the
      progression to androgen-independent (AI) disease. The term AI may not be entirely
      correct, in that recent data suggest that expression of androgen receptor (AR)
      and androgen-regulated genes is the primary association with prostate cancer
      progression after hormone ablation. Therefore, signaling through other growth
      factors has been thought to play a role in AR-mediated prostate cancer
      progression to AI disease in the absence of androgen ligand. However, existing
      data on how IGF-IR signaling interacts with AR activation in prostate cancer are
      conflicting. In this Prospect article, we review some of the published data on
      the mechanisms of IGF-IR/AR interaction and present new evidence that IGF-IR
      signaling may modulate AR compartmentation and thus alter AR activity in prostate
      cancer cells. Inhibition of IGF-IR signaling can result in cytoplasmic AR
      retention and a significant change in androgen-regulated gene expression.
      Translocation of AR from the cytoplasm to the nucleus may be associated with IGF
      induced dephosphorylation. Since fully humanized antibodies targeting the IGF-IR
      are now in clinical trials, the current review is intended to reveal the
      mechanisms of potential therapeutic effects of these antibodies on AI prostate
      cancers.

PMID- 16639716
TI  - Physiologically based pharmacokinetic modelling 2: predicting the tissue
      distribution of acids, very weak bases, neutrals and zwitterions.
AB  - A key component of whole body physiologically based pharmacokinetic (WBPBPK)
      models is the tissue-to-plasma water partition coefficients (Kpu's). The
      predictability of Kpu values using mechanistically derived equations has been
      investigated for 7 very weak bases, 20 acids, 4 neutral drugs and 8 zwitterions
      in rat adipose, bone, brain, gut, heart, kidney, liver, lung, muscle, pancreas,
      skin, spleen and thymus. These equations incorporate expressions for dissolution
      in tissue water and, partitioning into neutral lipids and neutral phospholipids.
      Additionally, associations with acidic phospholipids were incorporated for
      zwitterions with a highly basic functionality, or extracellular proteins for the
      other compound classes. The affinity for these cellular constituents was
      determined from blood cell data or plasma protein binding, respectively. These
      equations assume drugs are passively distributed and that processes are
      nonsaturating. Resultant Kpu predictions were more accurate when compared to
      published equations, with 84% as opposed to 61% of the predicted values agreeing
      with experimental values to within a factor of 3. This improvement was largely
      due to the incorporation of distribution processes related to drug ionisation, an
      issue that is not addressed in earlier equations. Such advancements in parameter
      prediction will assist WBPBPK modelling, where time, cost and labour requirements
      greatly deter its application.

PMID- 16639717
TI  - Direct patterning of centrosome arrays as templates for the assembly of
      microtubules.
AB  - We have achieved, for the first time, the selective patterning of centrosomes
      onto solid substrates. The use of such patterned centrosome arrays as templates
      for the directed polymerization of microtubules was also demonstrated.
      Centrosomes are small organelles in animal cells that serve as nucleation and
      organization centers of microtubules. Directed assembly of microtubules on the
      patterned centrosome arrays provides a new route to control the positions and
      directions of microtubules on surfaces. Combining the patterning of the isolated
      centrosomes and the directed growth of microtubules may lead to the generation of
      desired microtubule networks for bio-based nanodevices.

PMID- 16639718
TI  - In vitro hemolysis: guidance for the pharmaceutical scientist.
AB  - Pharmaceutical excipients are commonly incorporated into parenteral formulations
      to increase solubility and stability of active pharmaceutical ingredients. The
      biocompatibility of these excipients is an important consideration during
      formulation development. Despite the importance of hemolytic potential of
      parenteral formulations, there is considerable contradictory information in the
      literature related to the hemolytic potential of various excipients. The
      hemolytic potential of various formulation vehicles in dog, rabbit, and human
      blood by means of an in vitro hemolysis assay is compared. The selected
      formulation vehicles are found in currently marketed drug products. The guidance
      presented here considers formulations with a hemolysis value of <10% to be
      nonhemolytic while values > 25% to be at risk for hemolysis.

PMID- 16639719
TI  - Enzymes involved in the bioconversion of ester-based prodrugs.
AB  - Enzymes are essential for the activation of many prodrugs. In this review, the
      most important enzymes (e.g., paraoxonase, carboxylesterase,
      acetylcholinesterase, cholinesterase) involved in the bioconversion of ester
      based prodrugs will be discussed in terms of their biology and biochemistry. Most
      of these enzymes fall into the category of hydrolytic enzymes. However,
      nonhydrolytic enzymes, including cytochrome P450s, can also catalyze the
      bioconversion of ester prodrugs and thus will be discussed here. Other factors
      influencing the ability of these enzymes to catalyze the bioconversion of ester
      based prodrugs, particularly species and interindividual differences and
      stereochemical and structural features of the prodrugs, will be discussed.

PMID- 16639720
TI  - Predicting protein subcellular location by fusing multiple classifiers.
AB  - One of the fundamental goals in cell biology and proteomics is to identify the
      functions of proteins in the context of compartments that organize them in the
      cellular environment. Knowledge of subcellular locations of proteins can provide
      key hints for revealing their functions and understanding how they interact with
      each other in cellular networking. Unfortunately, it is both time-consuming and
      expensive to determine the localization of an uncharacterized protein in a living
      cell purely based on experiments. With the avalanche of newly found protein
      sequences emerging in the post genomic era, we are facing a critical challenge,
      that is, how to develop an automated method to fast and reliably identify their
      subcellular locations so as to be able to timely use them for basic research and
      drug discovery. In view of this, an ensemble classifier was developed by the
      approach of fusing many basic individual classifiers through a voting system.
      Each of these basic classifiers was trained in a different dimension of the
      amphiphilic pseudo amino acid composition (Chou [2005] Bioinformatics 21: 10-19).
      As a demonstration, predictions were performed with the fusion classifier for
      proteins among the following 14 localizations: (1) cell wall, (2) centriole, (3)
      chloroplast, (4) cytoplasm, (5) cytoskeleton, (6) endoplasmic reticulum, (7)
      extracellular, (8) Golgi apparatus, (9) lysosome, (10) mitochondria, (11)
      nucleus, (12) peroxisome, (13) plasma membrane, and (14) vacuole. The overall
      success rates thus obtained via the resubstitution test, jackknife test, and
      independent dataset test were all significantly higher than those by the existing
      classifiers. It is anticipated that the novel ensemble classifier may also become
      a very useful vehicle in classifying other attributes of proteins according to
      their sequences, such as membrane protein type, enzyme family/sub-family, G
      protein coupled receptor (GPCR) type, and structural class, among many others.
      The fusion ensemble classifier will be available at
      www.pami.sjtu.edu.cn/people/hbshen.

PMID- 16639721
TI  - Overexpression of Runx2 directed by the matrix metalloproteinase-13 promoter
      containing the AP-1 and Runx/RD/Cbfa sites alters bone remodeling in vivo.
AB  - The activator protein-1 (AP-1) and runt domain binding (Runx/RD/Cbfa) sites and
      their respective binding proteins, c-Fos/c-Jun and Runx2 (Cbfa1), regulate the
      rat matrix metalloproteinase-13 (MMP-13) promoter in both parathyroid hormone
      (PTH)-treated and differentiating osteoblastic cells in culture. To determine the
      importance of these regulatory sites in the expression of MMP-13 in vivo,
      transgenic mice containing either wild-type (-456 or -148) or AP-1 and
      Runx/RD/Cbfa sites mutated (-148A3R3) MMP-13 promoters fused with the E. coli
      lacZ reporter were generated. The wild-type transgenic lines expressed higher
      levels of bacterial beta-galactosidase in bone, teeth, and skin compared to the
      mutant and non-transgenic lines. Next, we investigated if overexpression of Runx2
      directed by the MMP-13 promoter regulated expression of bone specific genes in
      vivo, and whether this causes morphological changes in these animals. Real time
      RT-PCR experiments identified increased mRNA expression of bone forming genes and
      decreased MMP-13 in the tibiae of transgenic mice (14 days and 6 weeks old).
      Histomorphometric analyses of the proximal tibiae showed increased bone
      mineralization surface, mineral apposition rate, and bone formation rate in the
      transgenic mice which appears to be due to decreased osteoclast number. Since MMP
      13 is likely to play a role in recruiting osteoclasts to the bone surface,
      decreased expression of MMP-13 may cause reduced osteoclast-mediated bone
      resorption, resulting in greater bone formation in transgenic mice. In summary,
      we show here that the 148 bp upstream of the MMP-13 transcriptional start site is
      sufficient and necessary for gene expression in bone, teeth, and skin in vivo and
      the AP-1 and Runx/RD/Cbfa sites are likely to regulate this. Overexpression of
      Runx2 by these regulatory elements appears to alter the balance between the bone
      formation-bone resorption processes in vivo.

PMID- 16639722
TI  - Pharmacokinetics of 5-fluorouracil in the hamster following inhalation delivery
      of lipid-coated nanoparticles.
AB  - The inhalation delivery of 5-fluorouracil (5-FU) in lipid-coated nanoparticles
      (LNPs) to hamsters was evaluated to determine the feasibility for use in lung
      cancer chemotherapy. The inhaled dose, 30 mg LNPs/kg body weight (1.5 mg/kg 5
      FU), was delivered over an 8-min interval. Fluorescein isothiocyanate dextran
      (FITC-dextran) was included within the LNPs to provide an estimate of the
      particle concentration. The concentration of FITC-dextran and total 5-FU
      (released and LNP-associated) was determined as a function of time in the lung,
      trachea, larynx, esophagus, and serum. Concentrations of 5-FU and FITC-dextran
      were initially high in the trachea, larynx, and esophagus, and lower in the lung.
      Within 24 h, greater than 99% of the LNPs were cleared from the respiratory tract
      and total 5-FU concentrations mirrored the LNP concentration. An eight
      compartment pharmacokinetic model was used to describe the observed trends in
      concentrations of LNPs and total 5-FU and to estimate the released 5-FU
      concentration in the above tissues. From this analysis, effective local targeting
      as well as sustained efficacious concentrations of 5-FU in the expected tumor
      sites were demonstrated.

PMID- 16639723
TI  - Differential expression of HNF4alpha isoforms in liver stem cells and
      hepatocytes.
AB  - The hepatocyte nuclear factor (HNF4alpha) has been implicated in liver
      development and hepatocellular differentiation. The HNF4alpha expression in liver
      stem cells has not yet been fully investigated. Here, we describe the expression
      characterization of HNF4alpha in liver stem cells isolated from 2
      acetylaminofluorene/partial hepatectomy (AAF/PH) rat model by a combination of
      density-gradient centrifugation and selective enzymatic digestion. The obtained
      cells were identified by flow cytometry (FCM) immediately and then by
      immunocytochemisty and reverse transcription-polymerase chain reaction (RT-PCR)
      after 5 d culture. The cultured stem cells were subjected to analysis of the
      expression of various HNF4alpha isoforms using RT-PCR, Western blotting, and
      electrophoretic mobility shift assay (EMSA). Results showed that HNF4alpha
      isoforms, alpha1, alpha2, alpha7, and alpha8 were present in liver stem cells,
      which contrasted with only alpha1 and alpha2 expression in hepatocytes. The
      distinct expression patterns of HNF4alpha isoforms in liver stem cells may
      contribute to maintain the "stemness" of these cells.

PMID- 16639724
TI  - Protein transduction by lipidic peptide dendrimers.
AB  - We investigated the potential of a new family of lipidic peptide dendrimers in
      protein transduction into cultured cells. Dendrimer-protein interaction was
      determined by gel retardation assays using purified recombinant protein. To
      assess intracellular protein delivery, two marker proteins were used: recombinant
      firefly luciferase and a Cy3-labeled monoclonal antibody to the c-myc proto
      oncogene. Protein delivery was determined by luciferase assays and fluorescence
      microscopy, respectively. While there was minimal delivery of luciferase or
      antibody in the absence of the dendrimers, the latter increased protein delivery
      substantially. Luciferase delivery was concentration and cell type-dependent; the
      efficiency of delivery also varied with the number of terminal amino groups on
      the dendrimers. In previous reports, we showed that these dendrimers could be
      used for gene and drug delivery; the data we report herein suggest that they may
      also be capable of intracellular protein delivery. This finding has important
      implications for the use of these dendrimers in protein therapeutics and
      vaccinology.

PMID- 16639726
TI  - Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy.
AB  - Recent observations suggest that levodopa can induce irresistible sleep onset in
      multiple system atrophy (MSA). Therefore, we assessed sleepiness during a
      levodopa challenge in 17 MSA compared with 23 Parkinson's disease (PD) patients
      using the Stanford Sleepiness Scale (SSS). SSS scores during the levodopa
      challenge compared with baseline were significantly increased in the MSA compared
      with the PD group. These findings suggest greater potential of levodopa to induce
      sleepiness in MSA compared with PD, which may be related to differences in basal
      ganglia and brainstem pathology between the two disorders.

PMID- 16639727
TI  - New actigraph for long-term tremor recording.
AB  - A new method of movement analysis is validated, allowing an actigraph to
      discriminate tremor from other movements and store duration and intensity
      measures of both movement types. For algorithm optimization, wrist acceleration
      was recorded in nine controls and nine Parkinson's disease patients, while
      simultaneously rating their observed tremor minute by minute on item 20 of the
      Unified Parkinson's Disease Rating Scale. An optimization procedure to minimize
      false positives in controls while maximizing tremor detection in patients
      resulted in false positive tremor classification in 2.4% +/- 2.5% of the movement
      time of control subjects (range, 0%-7%), while providing tremor classification in
      82.1% +/- 15.4% of the movement time in patients (range, 55%-100%), correlating r
      = 0.93 with their averaged observed tremor score. A second, generalizability
      study showed that application of the optimized algorithm resulted in accurate
      classification of 71% +/- 14% of the observed tremor time (range, 46%-90%) in
      another 9 patients and in a false positive classification in only 0.5% +/- 0.8%
      of the time in another 10 controls (range, 0%-2.4%). The commercial availability
      of this actigraph now for the first time makes it possible to investigate tremor
      fluctuations over several weeks. An example is given of how long-term monitoring
      can be of use in evaluation of symptom management.

PMID- 16639728
TI  - Levodopa-responsive parkinsonism associated with hydrocephalus.
AB  - We report on a patient who developed acute parkinsonian symptoms following shunt
      revision for hydrocephalus. Parkinsonism improved dramatically after levodopa
      therapy. Furthermore, there was no recurrence of Parkinsonism despite
      discontinuation of levodopa. This observation suggests that Parkinsonism in this
      patient was caused by reversible dysfunction of the presynaptic nigrostriatal
      dopaminergic pathway due to hydrocephalus.

PMID- 16639729
TI  - Breast cancer incidence in U.S. radiologic technologists.
AB  - BACKGROUND: Studies of atomic bomb survivors and medically exposed populations
      have demonstrated an increased risk of breast cancer associated with acute or
      protracted, intermediate-dose or high-dose, ionizing radiation; however, the
      risks associated with low-dose and low-dose-rate (protracted) exposures are less
      certain. METHODS: The authors evaluated incident breast cancer risks from 1983 to
      1998 according to employment characteristics and a 4-level proxy index for
      cumulative radiation exposure based on 2 mail surveys among 56,436 U.S. female
      radiologic technologists who were certified from 1925 to 1980, adjusting for
      established breast cancer risk factors. RESULTS: During follow-up, 1050 new
      breast cancer diagnoses were ascertained. Compared with radiologic technologists
      who began working in 1970 or later, adjusted breast cancer risks for those who
      first worked in the 1960s, 1950s, 1940s, from 1935 to 1939, and before 1935 were
      1.0 (95% confidence interval [CI], 0.8-1.2), 1.2 (95% CI, 0.9-1.6), 1.0 (95% CI,
      0.7-1.5), 1.8 (95% CI, 1.0-3.2), and 2.9 (95% CI, 1.3-6.2), respectively. The
      risk rose with the number of years worked before 1940 (P value for trend = .002)
      and was elevated significantly among those who began working before age 17 years
      (relative risk, 2.6; 95% CI, 1.3-5.1; 10 women) but was not related to the total
      years worked in the 1940s or later. Compared with technologists who had a Level 1
      (minimal) proxy index for cumulative radiation exposure, breast cancer risks were
      1.0 (95% CI, 0.9-1.2), 1.0 (95% CI, 0.7-1.3), and 1.5 (95% CI, 1.0-2.2),
      respectively, for technologists who had Level 2, Level 3, and Level 4 (highest)
      exposure. CONCLUSIONS: Breast cancer risk was elevated significantly in female
      radiologic technologists who experienced daily low-dose radiation exposures over
      several years that potentially resulted in appreciable cumulative exposure. The
      increased risk for total years worked before 1940, but not later, was consistent
      with decreasing occupational radiation exposures, improvements in radiation
      technology, and more stringent radiation protection standards over time.

PMID- 16639730
TI  - Association between adiponectin, insulin resistance, and endometrial cancer.
AB  - BACKGROUND: Obesity is a well known risk factor for the development of
      endometrial cancer; however, weight alone does not account for all cases. The
      authors hypothesized that insulin resistance also contributes to an increased
      risk for endometrial cancer. Adiponectin is a protein secreted by adipose cells
      and has been shown to be a surrogate marker for insulin resistance, with low
      levels of adiponectin correlated with hyperinsulinemia and degree of insulin
      resistance. The purpose of the current study was to determine whether there was
      an independent association between adiponectin level and endometrial cancer.
      METHODS: A case-control study was performed on 117 endometrial cancer patients
      (cases) and 238 women with no history of cancer (controls). Serum adiponectin
      levels were measured using enzyme-linked immunoadsorbent assay and examined for
      their association with endometrial cancer. Univariate and multivariate logistic
      regression analyses were performed with adjustment for confounding factors.
      RESULTS: The mean serum adiponectin levels were significantly lower among cases
      (88.8+/-63.3 ng/mL) than among controls (148.2+/-68.3; P<.001). This inverse
      correlation continued to be observed after controlling for age, body mass index,
      diabetes, and hypertension. Cases were significantly more likely to have serum
      adiponectin levels in the lowest (odds ratio [OR] of 10.5; 95% confidence
      interval [95% CI], 4.49-24.57 [P<.001]) and intermediate tertiles (OR of 2.5; 95%
      CI, 1.01-6.21 [P=.05]) when compared with controls. CONCLUSIONS: Adiponectin
      level was found to be independently and inversely associated with endometrial
      cancer. Women with endometrial cancer were more likely to have low adiponectin
      levels than controls, even after adjusting for body mass index. This suggested
      that insulin resistance is independently associated with endometrial cancer.

PMID- 16639731
TI  - Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell
      support for high-risk primary breast carcinoma: follow-up at 12 years.
AB  - BACKGROUND: The authors previously reported results from a randomized trial of
      standard-dose chemotherapy with combined 5-fluorouracil (1000 mg/m2 per cycle),
      doxorubicin (50 mg/m2 per cycle), and cyclophosphamide (500 mg/m2 per cycle)
      (FAC) versus FAC followed by high-dose chemotherapy (HDCT) and autologous stem
      cell support (ASCS) for patients with high-risk primary breast carcinoma. After a
      median follow-up of 6.5 years, no significant differences were observed in
      recurrence-free survival (RFS) or overall survival (OS) between the 2 arms. This
      report updates the survival analyses. METHODS: Patients with >or=10 positive
      axillary lymph nodes after primary surgery or >or=4 positive lymph nodes at
      surgery after neoadjuvant chemotherapy were eligible. All patients were to
      receive 8 cycles of FAC. Patients were assigned randomly to receive either no
      further chemotherapy or 2 cycles of combined high-dose cyclophosphamide (5250
      mg/m2 per cycle), etoposide (1200 mg/m2 per cycle), and cisplatin (165 mg/m2 per
      cycle) with ASCS. Primary endpoints were RFS and OS. RFS and OS were calculated
      by using the Kaplan-Meier method. The log-rank statistic was used to compare
      treatment arms. RESULTS: Between 1990 and 1997, 78 patients were registered, and
      39 patients were assigned randomly to each arm. The median follow-up for all
      patients who were alive at last follow-up was 142.5 months (range, 45-169
      months). An intention-to-treat analysis showed no significant difference between
      the 2 arms in terms of RFS (at 10 years: 40% with FAC vs. 26% with FAC plus HDCT;
      P=.11) or OS (at 10 years: 47% with FAC vs. 42% with FAC plus HDCT; P=.13).
      CONCLUSIONS: With a median follow-up of nearly 12 years for patients who remained
      alive, this trial continued to demonstrate no RFS or OS advantage for patients
      with high-risk primary breast carcinoma treated with HDCT after standard-dose FAC
      chemotherapy.

PMID- 16639732
TI  - Health insurance coverage and cost barriers to needed medical care among U.S.
      adult cancer survivors age<65 years.
AB  - BACKGROUND: The health insurance and cost barriers to care among cancer survivors
      age <65 years were examined. METHODS: Using the 1998 and 2000 National Health
      Interview Survey, survivors ages 18 to 64 years (n=1718) were compared with
      similarly aged adults without cancer (n=50,276) to examine health insurance and
      reported delayed/missed needed medical care within the previous year because of
      cost. Findings were initially adjusted for age, sex, race, and ethnicity, and
      further adjusted for employment, income, health status, marital status, and
      region. RESULTS: Before adjustment, survivors were less likely to be uninsured
      (12.4% vs. 18.0%) and more likely to have public insurance (11.2% vs. 6.2%).
      After initial adjustment, survivors were as likely to lack insurance, less likely
      to have private insurance, and more likely to have public insurance. After
      further adjusting, differences in being uninsured were found to be small,
      differences in having private insurance were eliminated, and differences in
      having public insurance were reduced. Survivors most likely to lack insurance
      were younger, female, African-American, or lower income. Survivors, particularly
      uninsured or publicly insured survivors, were more likely to delay/miss care
      because of cost. Overall, 20.9% of survivors, including 68% of uninsured
      survivors, reported delaying/missing needed care. CONCLUSIONS: Health insurance
      coverage among cancer survivors age<65 years appears to be comparable to that of
      adults of similar age, sex, race, and ethnicity, but survivors may more likely be
      publicly insured. Differences are attributable in part to employment, income, and
      health status, factors potentially influenced by cancer. Unmet medical care needs
      because of cost were common among survivors, particularly uninsured survivors.

PMID- 16639733
TI  - Dietary selenium intake, aldehyde dehydrogenase-2 and X-ray repair cross
      complementing 1 genetic polymorphisms, and the risk of esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: To the authors' knowledge, few studies have been conducted to date
      regarding dietary selenium and the potential gene-nutrient interactions with
      single-nucleotide polymorphisms (SNPs) in different pathways on the risk of
      esophageal cancer. METHODS: The authors investigated the role of dietary selenium
      intake and its interplay with SNPs of the ALDH2 (glutamic acid [Glu] 487 lysine
      [Lys]) and the X-ray repair cross-complementing 1 (XRCC1) (arginine [Arg] 399
      glutamine [Gln]) genes on the risk of esophageal squamous cell carcinoma (ESCC)
      in a population-based, case-control study in China. In total, 218 patients with
      ESCC and 415 healthy population control participants were interviewed. Dietary
      selenium intake was estimated from a food frequency questionnaire with 97 food
      items. ALDH2 and XRCC1 polymorphisms were detected with a polymerase chain
      reaction-restriction fragment length polymorphism assay. RESULTS: The adjusted
      odds ratio (OR) for the highest quintile of dietary selenium intake, compared
      with the lowest quintile of intake, was 0.48 (95% confidence interval [95% CI],
      0.25-0.89), with a strong dose-response relation (P for trend, <.01). The ALDH2
      Lys and XRCC1 Gln variant alleles were associated with an increased risk of ESCC
      with adjusted ORs of 1.91 (95% CI, 0.96-3.80) and 1.67 (95% CI, 1.08-2.59),
      respectively. An elevation of the risk for ESCC was pronounced most among
      carriers of ALDH2 Lys/Lys and XRCC1 399Gln/Gln or Gln/Arg who consumed a low
      level of dietary selenium (adjusted OR, 4.16; 95% CI, 1.14-15.12). CONCLUSIONS:
      To the authors' knowledge, this is the first in-depth study to suggest that
      genetic susceptibility may modify the association between selenium intake and the
      risk of ESCC. The findings indicated that individuals with low dietary selenium
      intake and ALDH2 Lys/Lys and XRCC1 399Gln/Gln or Gln/Arg genotypes were
      associated with an increased ESCC risk, especially in the presence of exposure to
      tobacco and alcohol carcinogens.

PMID- 16639734
TI  - Impact of age on outcome of pediatric acute myeloid leukemia: a report from 2
      institutions.
AB  - BACKGROUND: The prognostic significance of age among pediatric patients with
      acute myeloid leukemia (AML) was investigated. METHODS: The authors reviewed the
      outcome of 424 patients who were <or=21 years of age at the time of diagnosis of
      AML (excluding acute promyelocytic leukemia) between 1983 and 2002 at St. Jude
      Children's Research Hospital (n=288) or the M. D. Anderson Cancer Center (n=136).
      Two treatment eras (1983-1989 and 1990-2002) were examined because of the greater
      intensity of treatment during the recent era. RESULTS: After controlling for the
      effects of cytogenetics, white blood cell (WBC) count, French-American-British
      (FAB) subtype, and treatment era, they observed that age and treatment era
      interacted significantly in relation to event-free survival (EFS) (P=.033).
      Patients 10 years of age or older were at greater risk of an adverse event than
      younger patients in the recent era (hazard ratio=1.8; 95% confidence interval
      [CI]: 1.3-2.6; P=.005) but not in the early era. The rate of adverse events
      (death or recurrence) increased significantly with each year of age in the recent
      era (4.3%/year; 95% CI: 1.9-6.8%; P=.001) but not in the early era. The rate of
      death increased significantly with each year of age in both eras (4.4%/year; 95%
      CI: 2.3-6.5%; P<.001). EFS and survival showed no association with study site,
      and the effects of age were similar at the 2 sites. CONCLUSIONS: These results
      suggest that age is an independent prognostic factor in childhood AML and that
      children younger than 10 years benefit more than older children from newer
      intensive therapies.

PMID- 16639735
TI  - Use of nutritional supplements in Parkinson's disease patients.
AB  - The use of nutritional supplements has almost doubled in the elderly population
      in the United States (US) in the past decade. We evaluated the use of nutritional
      supplements in Parkinson's disease (PD) patients to determine the prevalence of
      their use and whether patients were aware of possible side effects and drug
      interactions in the supplements they were taking. Consecutively selected PD
      patients from an academic movement disorders center completed a 33-item
      questionnaire regarding their use of nutritional supplements. A total of 120 PD
      patients completed the questionnaire and were included in the data analysis (mean
      age +/- SD = 68.2 +/- 11.65 years, 67 [55.8%] men and 53 women). Seventy-six
      patients (63%) took nutritional supplements at the time of data collection.
      Vitamins were the most common nutritional supplements used, and vitamin E was the
      most commonly used vitamin. Thirty-six patients (47%) who took nutritional
      supplements consulted with their doctor before taking them, and only 4% of
      patients who took nutritional supplements were aware of possible side effects
      from their use. Twenty patients (16.7%) reported that they were currently taking
      nutritional supplements because of symptoms related to their Parkinson's disease.
      The vast majority of PD patients surveyed were not aware that nutritional
      supplements could cause adverse side effects. Less than half of the patients who
      took nutritional supplements consulted their physician before starting them.
      Greater awareness of nutritional supplement use in PD patients is warranted to
      avoid potentially harmful effects and drug interactions.

PMID- 16639736
TI  - Characteristics of patients and predictors of in-hospital mortality after
      hospitalization for head and neck cancers.
AB  - BACKGROUND: The objectives of this study were to describe the characteristics of
      patients who were hospitalized for head and neck cancer (HNC) during the years
      2000 through 2003 and to identify predictors of in-hospital mortality. METHODS:
      The Nationwide Inpatient Sample for the years 2000 through 2003 was used. All
      patients who had a primary diagnosis of any of the HNCs were included in the
      study. Univariate and multivariate logistic regression analyses were used to
      identify patient and hospital characteristics that were associated with in
      hospital mortality. RESULTS: In total, 24,803 patients were hospitalized for
      HNCs. The average age of patients was 62 years, the mean length of stay in the
      hospital was 7.89 days, and the in-hospital mortality rate was 5.18%. Patients
      who had comorbid conditions and complications and patients who were grouped under
      the self-pay/no charge/others category had greater odds of in-hospital mortality
      compared with patients who were covered by private insurance (P<.02). Patients
      who were treated in large-bed, urban, or teaching hospitals had lower odds of in
      hospital mortality compared with patients who were treated in small or medium
      bed, rural, or nonteaching hospitals, respectively (P<.03). CONCLUSIONS: Patients
      with comorbid conditions and complications and patients without adequate
      insurance coverage had greater odds of in-hospital mortality. One reason for this
      may be inadequate access to care because of the absence of insurance or
      underinsurance. Further studies controlling for disease stage will be required to
      determine whether insurance status and patient-related factors can influence
      outcomes from HNC in individual patients independent of their disease stage.

PMID- 16639737
TI  - A phase II trial of pegylated interferon alpha-2b therapy for polycythemia vera
      and essential thrombocythemia: feasibility, clinical and biologic effects, and
      impact on quality of life.
AB  - BACKGROUND: Conventional interferon-alpha (IFN) is an effective treatment for
      patients with myeloproliferative disorders. However, many patients discontinue
      therapy because of side effects. METHODS: In this 24-month, Phase II feasibility
      study of pegylated interferon alpha-2b (PEG-IFN) treatment, a starting dose of
      0.5 microg/kg per week was received by 21 patients with polycythemia vera (PV)
      and 21 patients with essential thrombocythemia (ET). The treatment objective, a
      complete platelet response (CR), was a platelet count<400x10(9)/L in symptomatic
      patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera-1
      (PRV-1) messenger RNA expression was analyzed prior to and during therapy.
      Quality of life (QoL) was investigated by using the European Organization for
      Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: At 6 months, 29
      of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was
      not related to diagnosis, gender, or previous therapy. Nineteen patients
      completed the planned 2-year treatment in CR. No thromboembolic or bleeding
      complications were observed. Phlebotomy requirements were reduced in the majority
      of patients with PV. Five of 14 patients (36%) who initially were positive for
      PRV-1 achieved normalized PRV-1 expression under PEG-IFN treatment. Side effects
      were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19
      patients reported any side effects at 2 years. The QLQ-C30 revealed clinically
      significant impairments in several aspects of QoL at 6 months; however, at 2
      years, QoL measurements were not different from baseline. CONCLUSIONS: PEG-IFN
      effectively reduced platelet counts in 29 of 42 patients, but only 19 patients
      maintained a CR at 2 years. The reversal of PRV-1 positivity noted in a subset of
      patients suggested that PEG-IFN may have an effect on the malignant clone. PEG
      IFN is a valuable therapeutic alternative for patients who tolerate its initial
      side effects.

PMID- 16639738
TI  - Generalizability of cancer clinical trial results: prognostic differences between
      participants and nonparticipants.
AB  - BACKGROUND: The generalizability of clinical trial results is questionable,
      because fewer than 5% of cancer patients participate. The authors examined the
      comparability of clinical trial participants and nonparticipants and the
      potential impact of differences. METHODS: A retrospective cohort of 19,340 cancer
      patients who were diagnosed between January 1990 and December 1997 was
      characterized by trial participation. The distributions of prognostically
      important factors among trial participants were compared with the distributions
      among nonparticipants and the population of patients diagnosed during the same
      period in the Surveillance, Epidemiology, and End Results population. The impact
      of these factors on survival was examined by using a Cox proportional hazards
      analysis. RESULTS: Trial participants were younger and had better performance
      status and fewer comorbid conditions compared with nonparticipants. However,
      participants were more likely to have locally advanced disease, positive lymph
      node status, poorly differentiated tumors, liver metastases, and multiple
      metastatic sites. The former factors were associated with significantly longer
      survival, whereas the later factors were associated with significantly shorter
      survival. CONCLUSIONS: The lack of comparability between trial participants and
      nonparticipants called into question the generalizability of clinical trial
      results. Although selective recruitment for clinical trials is justified, the
      authors encourage the use of population-based trials of effectiveness in "all
      comers."

PMID- 16639740
TI  - Iatrogenic botulism in an amateur weight-lifter.

PMID- 16639739
TI  - Phase II study of temozolomide plus pegylated interferon-alpha-2b for metastatic
      melanoma.
AB  - BACKGROUND: Temozolomide and interferon-alpha-2b (IFN-alpha-2b) are both active
      in melanoma. Therefore, the efficacy and safety of temozolomide in combination
      with pegylated IFN-alpha-2b in patients with metastatic melanoma without brain
      metastases was investigated. METHODS: Patients with histologically confirmed,
      unresectable, American Joint Committee on Cancer Stage IV melanoma were enrolled
      in an open-label, Phase II study. The primary endpoints were tumor response and
      safety. Patients received temozolomide (75 mg/m2/dayx6 weeks with a 2-week break
      between cycles) plus concomitant subcutaneous pegylated IFN-alpha-2b (0.5
      microg/kg/wk, continuously). Treatment was continued until unacceptable toxicity
      or disease progression occurred. RESULTS: Thirty-five patients (median age, 55
      years) with Stage IV melanoma and a median of 3 metastatic sites were enrolled
      and received a median of 1 cycle (i.e., 8 weeks) of therapy (range, 0-6 cycles).
      Eleven patients (31%) (95% confidence interval, 16% to 47%) had an objective
      tumor response, including 3 with clinical complete response durations of 6
      months, 20 months, and 32+ months and 8 with partial responses. Three patients
      with a partial or mixed response were subsequently rendered free of clinically
      detectable disease with surgery. The median survival was 12 months with a median
      follow-up among survivors of 16 months. No patient developed brain metastases
      while receiving study treatment. Treatment was generally well tolerated.
      Hematologic toxicity consisted mainly of lymphopenia and leukopenia (National
      Cancer Institute Common Toxicity Criteria Grades 1-3); no Grade 4 hematologic
      toxicity was observed. CONCLUSIONS: The combination of temozolomide plus
      pegylated IFN-alpha-2b had antitumor activity and was well tolerated in patients
      with metastatic melanoma. Therefore, further study is warranted.

PMID- 16639741
TI  - Processing the spatial configuration of complex actions involves right posterior
      parietal cortex: An fMRI study with clinical implications.
AB  - The left hemispheric dominance for complex motor behavior is undisputed. Clinical
      observations of complex motor deficits in patients with right hemispheric
      lesions, however, suggest an additional contribution of the right hemisphere to
      higher motor control. We assessed, using functional MRI (fMRI), which brain
      regions are implicated in processing the spatial aspects of complex, object
      related actions. Using a blocked, factorial design, 17 healthy volunteers were
      asked to detect either spatial or sequential errors (factor ERROR) in complex
      activities of daily living, presented as video sequences with the appropriate
      object(s) or as pantomimes (factor STIMULUS). Observing complex actions
      (irrespective of stimulus type) activated a bilateral frontoparietal network.
      Observing actions with objects (relative to pantomimes) differentially increased
      neural activity in the fusiform gyrus and inferior occipital cortex bilaterally.
      Observing pantomimes, i.e., the same actions but without any object,
      differentially activated right prefrontal cortex, anterior cingulate cortex, the
      precuneus, and left cerebellum. The left cingulate cortex was differentially
      activated when subjects assessed the sequencing of actions. By contrast,
      assessing the spatial configuration of complex actions differentially increased
      neural activity in right posterior parietal cortex. A significant interaction of
      ERROR and STIMULUS was revealed for the right inferior parietal cortex only.
      These findings suggest a specific role of the right hemisphere, especially of
      right posterior parietal cortex, in processing spatial aspects of complex actions
      and thus provide a physiological basis for the observed apraxic motor deficits in
      patients with right hemispheric damage.

PMID- 16639742
TI  - Late acquisition of literacy in a native language.
AB  - With event-related functional MRI (fMRI) and with behavioral measures we studied
      the brain processes underlying the acquisition of native language literacy. Adult
      dialect speakers were scanned while reading words belonging to three different
      conditions: dialect words, i.e., the native language in which subjects are
      illiterate (dialect), German words, i.e., the second language in which subjects
      are literate, and pseudo-words. Investigating literacy acquisition of a dialect
      may reveal how novel readers of a language build an orthographic lexicon, i.e.,
      establish a link between already available semantic and phonological
      representations and new orthographic word forms. The main results of the study
      indicate that a set of regions, including the left anterior hippocampal formation
      and subcortical nuclei, is involved in the buildup of orthographic
      representations. The repeated exposure to written dialect words resulted in a
      convergence of the neural substrate to that of the language in which these
      subjects were already proficient readers. The latter result is compatible with a
      "fast" brain plasticity process that may be related to a shift of reading
      strategies.

PMID- 16639743
TI  - Kinetics of the interaction of desAABB-fibrin monomer with immobilized
      fibrinogen.
AB  - The soluble and stable fibrin monomer-fibrinogen complex (SF) is well known to be
      present in the circulating blood of healthy individuals and of patients with
      thrombotic diseases. However, its physiological role is not yet fully understood.
      To deepen our knowledge about this complex, a method for the quantitative
      analysis of interaction between soluble fibrin monomers and surface-immobilized
      fibrinogen has been established by means of resonant mirror (IAsys) and surface
      plasmon resonance (BIAcore) biosensors. The protocols have been optimized and
      validated by choosing appropriate immobilization procedures with regeneration
      steps and suitable fibrin concentrations. The highly specific binding of fibrin
      monomers to immobilized fibrin(ogen), or vice versa, was characterized by an
      affinity constant of approximately 10(-8)M, which accords better with the direct
      dissociation of fibrin triads (KD approximately 10(-8) -10(-9) M) (J. R. Shainoff
      and B. N. Dardik, Annals of the New York Academy of Science, 1983, Vol. 27, pp.
      254-268) than with earlier estimations of the KD for the fibrin-fibrinogen
      complex (KD approximately 10(-6) M) (J. L. Usero, C. Izquierdo, F. J. Burguillo,
      M. G. Roig, A. del Arco, and M. A. Herraez, International Journal of
      Biochemistry, 1981, Vol. 13, pp. 1191-1196).

PMID- 16639744
TI  - Evaluation of bone regeneration by DNA release from composites of
      oligo(poly(ethylene glycol) fumarate) and cationized gelatin microspheres in a
      critical-sized calvarial defect.
AB  - This research examines the bone formation response to release of plasmid DNA
      encoding human Bone Morphogenetic Protein-2 from hydrogel composites consisting
      of cationized gelatin microspheres (CGMS) embedded within a crosslinked
      oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel network in a critical-sized
      rat cranial defect model after 30 days. Four composite groups were investigated:
      (1) composites with 10 microg DNA loaded into the CGMS phase, (2) composites with
      10 microg DNA loaded into the OPF phase, (3) composites with 100 microg DNA
      loaded into the OPF phase, and (4) composites without DNA (material control).
      Light microscopy revealed no enhancement in bone formation for groups releasing
      plasmid DNA, relative to the material control group. Limited formation of new
      bone was observed from the defect margins and within the defect for some samples.
      The hydrogels swelled appreciably and fragmentation of the implants was noted to
      varying degrees among samples within groups, with a presence of inflammatory
      cells related to the degree of fragmentation. The lack of enhancement in bone
      formation indicates that the release of plasmid DNA from the composites was not
      sufficient to elicit a bone regeneration response.

PMID- 16639745
TI  - Multiple molecular dynamics simulations of human p450 monooxygenase CYP2C9: the
      molecular basis of substrate binding and regioselectivity toward warfarin.
AB  - To examine the molecular basis of activity and regioselectivity of the clinically
      important human microsomal cytochrome P450 (CYP) monooxygenase 2C9 toward its
      substrate warfarin, 22 molecular dynamics simulations (3-5 ns each) were
      performed in the presence and absence of warfarin. The resulting trajectories
      revealed a stable protein core and mobile surface elements. This mobility leads
      to the formation of two surface channels in the region between F-G loop, B'
      helix/B-B' loop, beta(1)-sheet, and between helices F and I and the turn in the C
      terminal antiparallel beta-sheet in the presence of warfarin. Besides the
      nonproductive state of the CYP2C9 warfarin complex captured in the crystal
      structure, three additional states were observed. These states differ in the
      shape of the substrate binding cavity and the position of the warfarin molecule
      relative to heme. In one of these states, the 7- and 6-positions of warfarin
      contact the heme with a marked geometrical preference for position 7 over
      position 6. This modeling result is consistent with experimentally determined
      regioselectivity (71 and 22% hydroxylation in positions 7 and 6, respectively).
      Access to the heme group is limited by the core amino acids Ala297, Leu362,
      Leu366, and Thr301, which therefore are expected to have a major impact on
      regioselectivity. In addition, modeling predicts that autoactivation of warfarin
      is sterically hindered. Our study demonstrates how the combination of mobile
      surface and rigid core leads to interesting properties: a broad substrate profile
      and simultaneously a high regioselectivity.

PMID- 16639746
TI  - Assessing the acid-base and conformational properties of histidine residues in
      human prion protein (125-228) by means of pK(a) calculations and molecular
      dynamics simulations.
AB  - A thorough study of the acid-base behavior of the four histidines and the other
      titratable residues of the structured domain of human prion protein (125-228) is
      presented. By using multi-tautomer electrostatic calculations, average titration
      curves have been built for all titratable residues, using the whole bundles of
      NMR structures determined at pH 4.5 and 7.0. According to our results, (1) only
      histidine residues are likely to be involved in the first steps of the pH-driven
      conformational transition of prion protein; (2) the pK(a)'s of His140 and His177
      are approximately 7.0, whereas those of His155 and His187 are < 5.5. 10-ns long
      molecular dynamics simulations have been performed on five different models,
      corresponding to the most significant combinations of histidine protonation
      states. A critical comparison between the available NMR structures and our
      computational results (1) confirms that His155 and His187 are the residues whose
      protonation is involved in the conformational rearrangement of huPrP in mildly
      acidic condition, and (2) shows how their protonation leads to the
      destructuration of the C-terminal part of HB and to the loss of the last turn of
      HA that represent the crucial microscopic steps of the rearrangement.

PMID- 16639747
TI  - Structure of a glutathione conjugate bound to the active site of aldose
      reductase.
AB  - Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that
      catalyzes the reduction of aldehydes, ketones, and aldo-sugars. AR has been
      linked to the development of hyperglycemic injury and is a clinical target for
      the treatment of secondary diabetic complications. In addition to reducing
      glucose, AR is key regulator of cell signaling through it's reduction of
      aldehydes derived from lipoproteins and membrane phospholipids. AR catalyzes the
      reduction of glutathione conjugates of unsaturated aldehydes with higher
      catalytic efficiency than free aldehydes. The X-ray structure of human AR
      holoenzyme in complex with the glutathione analogue S-(1,2-dicarboxyethyl)
      glutathione (DCEG) was determined at a resolution of 1.94 A. The distal
      carboxylate group of DCEG's dicarboxyethyl moiety interacted with the conserved
      AR anion binding site residues Tyr48, His110, and Trp111. The bound DCEG's
      glutathione backbone adopted the low-energy Y-shape form. The C-terminal
      carboxylate of DCEG glutathione's glycine formed hydrogen bonds to Leu301 and
      Ser302, while the remaining interactions between DCEG and AR were hydrophobic,
      permitting significant flexibility of the AR and glutathione (GS) analogue
      interaction. The observed conformation and interactions of DCEG with AR were
      consistent with our previously published molecular dynamics model of glutathionyl
      propanal binding to AR. The current structure identifies major interactions of
      glutathione conjugates with the AR active-site residues.

PMID- 16639748
TI  - Association of calcineurin with mitochondrial proteins.
AB  - Using mouse hearts from Swiss Webster mice, calcineurin was immunoprecipitated
      using commercially available anti-calcineurin antibody and the resulting complex
      analyzed by using sodium dodecyl sulfate-gel electrophoresis with silver
      staining. Distinct proteins were observed and subjected to in situ trypsin
      digestion followed by extraction of the resulting peptides. Peptides from each
      protein band were loaded onto a target for matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and analyzed. The
      resulting peptide mass spectrum was compared with the Mascot and Protein
      Prospector databases and resulted in the specific identification of heart
      mitochondrial proteins, specifically Mn-superoxide dismutase (SOD), aconitase
      (ACN), and malate dehydrogenase (MDH). Each of the three mitochondrial enzymes
      was identified with approximately 15-25% sequence coverage and all with
      statistical significance (P < 0.05) according to the Mascot database search
      engine. Tandem mass spectrometry analysis of the peptide fragmentation spectra
      confirmed the identification of these protein partners and also yielded the
      identification of mitochondrial isocitrate dehydrogenase (ICDH) as another
      protein in the immunoprecipitated complex. Using antibody preparations against Mn
      SOD, ACN, and ICDH showed the presence of calcineurin and each of the three
      proteins in the immunoprecipitated complex by Western slot blotting. The activity
      of ACN, but not MDH or ICDH, was enhanced after incubation with calcineurin
      indicating one possible regulatory function for the complex. The mitochondrial
      forms of Mn-SOD, ACN, MDH, and ICDH were identified as partner proteins of
      calcineurin with all the proteins present in a single multiprotein complex.

PMID- 16639749
TI  - Tunable DNA cleavage by intercalating peptidoconjugates.
AB  - The properties of a novel family of peptide-based DNA-cleavage agents are
      described. Examination of the DNA-cleavage activities of a systematic series of
      peptide-intercalator conjugates revealed trends that show a strong dependence on
      peptide sequence. Conjugates differing by a single residue displayed reactivities
      that varied over a wide range. The cleavage activity was modulated by the
      electrostatic or steric qualities of individual amino acids. Isomeric conjugates
      that differed in the position of the tether also exhibited different
      reactivities. The mechanism of DNA cleavage for these compounds was also probed
      and was determined to involve hydrogen-atom abstraction from the DNA backbone.
      Previous studies of these compounds indicated that amino acid peroxides were the
      active agents in the cleavage reaction; in this report, the chemistry underlying
      the reaction is characterized. The results reported provide insight into how
      peptide sequences can be manipulated to produce biomimetic compounds.

PMID- 16639751
TI  - Au(I)-catalyzed tandem [3,3] rearrangement-intramolecular hydroarylation: mild
      and efficient formation of substituted indenes.

PMID- 16639752
TI  - Subpyriporphyrin--a[14]triphyrin(1.1.1) homologue with an embedded pyridine
      moiety.

PMID- 16639753
TI  - High-throughput carbohydrate microarray analysis of 24 lectins.

PMID- 16639754
TI  - A highly enantioselective Bronsted acid catalyzed cascade reaction:
      organocatalytic transfer hydrogenation of quinolines and their application in the
      synthesis of alkaloids.

PMID- 16639755
TI  - Thermal production and reactions of organic ions at atmospheric pressure.

PMID- 16639756
TI  - Kinetically controlled ligation for the convergent chemical synthesis of
      proteins.

PMID- 16639757
TI  - Chiral 4-phenyl-2-trifluoromethyloxazolidine: a high-performance chiral auxiliary
      for the alkylation of amides.

PMID- 16639758
TI  - Lithiation/electrophilic quench of [(eta5-cyclohexadienyl)Mn(CO)3]: Versatile
      functionalization and resolution of planar chirality in the organomanganese
      series.

PMID- 16639759
TI  - Not unhydrolyzed at pH 8.

PMID- 16639760
TI  - Epitaxial growth of peptide nanofilaments on inorganic surfaces: effects of
      interfacial hydrophobicity/hydrophilicity.

PMID- 16639761
TI  - Ultrastable particle-stabilized foams.

PMID- 16639762
TI  - Ultrastable gold nanocatalyst supported by nanosized non-oxide substrate.

PMID- 16639763
TI  - Enhanced signals and fast nucleic acid hybridization by microfluidic chaotic
      mixing.

PMID- 16639764
TI  - Size-dependent oxidation mechanism of supported Pd nanoparticles.

PMID- 16639765
TI  - Watson-Crick base-pairing properties of nucleic acid analogues with
      stereocontrolled alpha and beta torsion angles (alpha,beta-D-CNAs).

PMID- 16639766
TI  - Multivalent dendrons for high-affinity adhesion of proteins to DNA.

PMID- 16639767
TI  - A new reaction pathway in organophosphorus chemistry: competing S(N)2 and AE'
      pathways for nucleophilic attack at a phosphorus-carbon cage compound.

PMID- 16639768
TI  - A general synthesis of C6-azolyl purine nucleosides.

PMID- 16639769
TI  - A nanowire-nanoparticle cross-linking approach to highly porous electrically
      conducting solids.

PMID- 16639770
TI  - Revising the highest oxidation states of the 5d elements: the case of
      iridium(+VII).

PMID- 16639771
TI  - A nickel-alkyl bond in an inactivated state of the enzyme catalyzing methane
      formation.

PMID- 16639772
TI  - A highly active catalyst for Suzuki-Miyaura cross-coupling reactions of
      heteroaryl compounds.

PMID- 16639773
TI  - Committee for Medicinal Products for Human Use (CHMP) guideline on the choice of
      the non-inferiority margin.

PMID- 16639774
TI  - Diagnostics for assumptions in moderate to large simple clinical trials: do they
      really help?

PMID- 16639775
TI  - Committee for Medicinal Products for Human Use (CHMP) guideline on Data
      Monitoring Committees.

PMID- 16639776
TI  - An introductory note to CHMP guidelines: choice of the non-inferiority margin and
      data monitoring committees.
AB  - The Committee on Medical Products for Human Use (CHMP) has recently issued two
      new guidance documents that are of particular note to statisticians. The purpose
      of this short note is to give a little background to the origins of these
      documents and a flavour of some of their most important features. The two
      guidelines are reproduced as the next two papers in the journal.

PMID- 16639777
TI  - Simple improved confidence intervals for comparing matched proportions.

PMID- 16639778
TI  - Heart imaging. Matching the best view to you.

PMID- 16639779
TI  - Fish oil not effective in preventing heart arrhythmias in some.

PMID- 16639780
TI  - Healing grief. Dealing with loss.

PMID- 16639781
TI  - I've read about people using human growth hormone to reverse aging. Does it
      really work?

PMID- 16639782
TI  - I've recently developed an allergy to sulfites. I'm wondering if fruits and
      vegetables are coated with sulfites and, if so, will washing or peeling them get
      rid of the sulfites?

PMID- 16639783
TI  - Viewpoint: where now for facilitated PCI?

PMID- 16639784
TI  - History of cardiology: telegrams from the heart.

PMID- 16639786
TI  - Abstracts of the 45th Annual Meeting of the Society of Toxicology, San Diego,
      California, USA, March 5-9, 2006.

PMID- 16639785
TI  - Letter regarding article by Coronel et al, "right ventricular fibrosis and
      conduction delay in a patient with clinical signs of Brugada syndrome: a combined
      electrophysiological, genetic, histopathologic, and computational study".

PMID- 16639787
TI  - Bibliography. Current world literature. Resuscitation and trauma anaesthesia.

PMID- 16639788
TI  - Bibliography. Current world literature. Ethics, economics and outcome.

PMID- 16639789
TI  - Mature taste receptor cells grown outside body.

PMID- 16639790
TI  - Success and failure in social norms interventions.

PMID- 16639791
TI  - Alcohol policy in Latin America.

PMID- 16639792
TI  - Child abuse & neglect. The responsibility of the dental community.

PMID- 16639793
TI  - LSU School of Dentistry. From Textbooks to laptops.

PMID- 16639794
TI  - Expert panel recommendations for the prevention, diagnosis, and treatment of
      osteonecrosis of the jaws.

PMID- 16639795
TI  - The buzz about bisphosphonates.

PMID- 16639796
TI  - New options for cholesterol control. As more drugs become available, here's
      advice on your best strategy.

PMID- 16639797
TI  - Aspirin's benefits: fewer heart attacks for him, fewer strokes for her.

PMID- 16639798
TI  - Non-surgical stroke protection. Doctors probe deep into brain arteries to ensure
      blood flow.

PMID- 16639799
TI  - How to stop the toll of stress. Fight a major heart threat--by learning to take
      it easy.

PMID- 16639801
TI  - My cardiologist said that I really need to start exercising. I really can't,
      though, because I have a bad back. What do you recommend?

PMID- 16639800
TI  - Adult with congenital defects. Many arent' aware of decades-old abnormalities.

PMID- 16639802
TI  - Board of Dentistry moves on emerging "national" exam.

PMID- 16639803
TI  - Testing your diagnostic skills. Case no. 1: inflammatory process (low grade B
      cell lymphoma).

PMID- 16639804
TI  - Treating odontogenic infections: an update for dental professionals.

PMID- 16639805
TI  - Recent reports link bisphosphonates use to osteonecrosis.

PMID- 16639806
TI  - In matters of life and death, forensic dentistry plays a pivotal role.

PMID- 16639807
TI  - New directions in kinetic high information content assays.

PMID- 16639808
TI  - Australia's notifiable diseases status, 2004, annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2004, 60 diseases and conditions were nationally notifiable in Australia.
      States and Territories reported a total of 110,929 cases of communicable diseases
      to the National Notifiable Diseases Surveillance System (NNDSS): an increase of 4
      per cent on the number of notifications in 2003. In 2004, the most frequently
      notified diseases were sexually transmissible infections (46,762 cases; 42% of
      total notifications), gastrointestinal diseases (25,247 cases; 23% of total
      notifications) and bloodborne diseases (19,191 cases; 17% of total
      notifications). There were 13,206 notifications of vaccine preventable diseases,
      6,000 notifications of vectorborne diseases, 1,799 notifications of other
      bacterial infections (includes, legionellosis, leprosy, meningococcal infections
      and tuberculosis) and 877 notifications of zoonotic diseases.

PMID- 16639809
TI  - Effects of pefloxacin in multi drug resistant typhoid fever.

PMID- 16639810
TI  - Must we really make the case for abortion rights all over again?

PMID- 16639811
TI  - Italy: fertile ground for reform.

PMID- 16639812
TI  - Reframing social justice, feminism and abortion.

PMID- 16639813
TI  - Experts give go-ahead for human stem cell research but safeguards are needed.

PMID- 16639814
TI  - All in our genes?

PMID- 16639815
TI  - Human embryonic cloning.

PMID- 16639816
TI  - Ethical aspects of human stem cell research and its use.

PMID- 16639817
TI  - Exploitation and commercial surrogate motherhood.

PMID- 16639818
TI  - A hitherto unnamed dermatologic entity with clinical features of both psoriasis
      and eczema.

PMID- 16639819
TI  - Human embryonic stem cell research.

PMID- 16639820
TI  - In vitro fertilisation: the science and the ethics in the 21st century.

PMID- 16639821
TI  - The challenge of genetic engineering to medical anthropology and ethics.

PMID- 16639822
TI  - Dentistry has vital role in women's health care.

PMID- 16639823
TI  - Testing your diagnostic skills. Case no. 1: ameloblastic fibro-odontoma.

PMID- 16639824
TI  - Dr. Friedel sets course for coming year.

PMID- 16639825
TI  - Position of the American Dietetic Association: food and nutrition misinformation.
AB  - It is the position of the American Dietetic Association (ADA) that food and
      nutrition misinformation can have harmful effects on the health, well-being, and
      economic status of consumers. Nationally credentialed dietetics professionals
      working in health care, academia, public health, the media, government, and the
      food industry are uniquely qualified to advocate for and promote science-based
      nutrition information to the public, function as primary nutrition educators to
      health professionals, and actively correct food and nutrition misinformation.
      Enormous scientific advances have been made in the area of food and nutrition,
      leading to a fine-tuning of recommendations about healthful eating. Consumers
      have become increasingly aware of the nutrition-health link and reliant on
      nutrition information to base their decisions, and have assumed partial
      responsibility for changing their eating behaviors. Unfortunately, these same
      trends also create opportunities for food and nutrition misinformation to
      flourish. News reports rarely provide enough context for consumers to interpret
      or apply the advice given, and preliminary findings often attract unmerited and
      misleading attention. Effective nutrition communication must be consumer-friendly
      and contain sufficient context to allow consumers to consider the information and
      determine whether it applies to their unique health and nutritional needs.
      Consistent with ADA's organizational vision that members "are the leading source
      of nutrition expertise," ADA recognizes its responsibility to help consumers
      identify food and nutrition misinformation in the following ways: (a) ADA members
      should provide consumers with sound, science-based nutrition information and help
      them to recognize misinformation; (b) ADA members need to be the primary source
      of sound, science-based nutrition information for the media and to inform them
      when misinformation is presented; and (c) ADA members should continue to
      diligently work with other health care practitioners, educators, policy makers,
      and food and dietary supplement industry representatives to responsibly address
      the health and psychological, physiological, and economic effects of nutrition
      related misinformation.

PMID- 16639826
TI  - The role of timing and intensity of rehabilitation therapies.

PMID- 16639827
TI  - American Dietetic Association: standards of practice and standards of
      professional performance for registered dietitians (generalist, specialty, and
      advanced) in behavioral health care.

PMID- 16639828
TI  - Jury to militant animal rights group: guilty.

PMID- 16639829
TI  - Improving energy use in veterinary clinics. Need for more energy-efficient
      businesses continues to grow.

PMID- 16639830
TI  - Insurance planning vital to veterinarians' financial future. HSAs, life and
      disability insurance can play key roles in planning.

PMID- 16639831
TI  - Nano neuro knitting repairs injured brain.

PMID- 16639832
TI  - Atorvastatin and glatiramer acetate: new hope in MS?

PMID- 16639833
TI  - Social life best prescription for mental stress?

PMID- 16639834
TI  - Boosting brain endocannabinoids in multiple sclerosis.

PMID- 16639835
TI  - Alzheimer's disease could be "type 3 diabetes".

PMID- 16639836
TI  - African meningitis belt: 2006.

PMID- 16639837
TI  - UK Biobank launched to mixed reception.

PMID- 16639838
TI  - [Resistance by oscillometry. Comparison of its behavior in patients with asthma
      and cystic fibrosis].
AB  - This study aims to assess the behavior of the oscillometric parameters in 60
      patients with bronchial asthma and in 39 with cystic fibrosis. All of them
      underwent an impulse oscillometry (IOS) and forced spirometry. The correlations
      existing between FEV1 and different oscillometric endpoints were assessed. In
      asthmatic subjects, the oscillometry parameters that correlated best with FEV1
      were impedance (Zsr) and resistance to 5 hertz (Rsr5), while it was the Zsr and
      reactance to 5 hertz (Xsr5) in the individuals with cystic fibrosis. In the last
      group of patients, no correlation was found between FEV1 and Rsr in most of the
      frequencies evaluated. We conclude that there are differences in the behavior of
      the oscillometric parameters in patients with bronchial asthma and cystic
      fibrosis. The oscillometric parameters having the greatest use in the detection
      of the obstruction to airflow vary according to the disease studied.

PMID- 16639839
TI  - Thoughts on veterinary medicine's public image.

PMID- 16639840
TI  - Comments on raw meat diets for dogs.

PMID- 16639841
TI  - Comments on raw meat diets for dogs.

PMID- 16639842
TI  - Comments on raw meat diets for dogs.

PMID- 16639843
TI  - Requests information on AVMA directory tagline.

PMID- 16639844
TI  - Thoughts on feral cats' role in public health.

PMID- 16639845
TI  - Of leaders and transformers: a tribute to Gretta Styles.

PMID- 16639846
TI  - The role of C-reactive protein in modern obstetric and gynecological practice.
AB  - C-reactive protein is an acute phase protein widely used as an indicator of
      infectious or inflammatory conditions. Traditionally it has been used as an
      adjunctive test for inflammation and as a marker of disease activity. Though
      sensitive, its nonspecific nature imposes limitation on its clinical use.
      Currently C-reactive protein is used in the management of chorioamnionitis,
      preterm premature rupture of membranes, pelvic inflammatory disease, and urinary
      tract infection. Interestingly, several obstetric conditions such as pre
      eclampsia and gestational diabetes are now known to have an underlying
      inflammatory basis and there is an emerging role of C-reactive protein testing in
      managing these diseases. Additionally C-reactive protein testing has an
      established place in management of several acute abdominal conditions. The aim of
      this paper is to review the place of C-reactive protein in modern obstetric and
      gynecological practice.

PMID- 16639847
TI  - On: Validation of psychoanalytic theories: toward a conceptualization of
      references.

PMID- 16639848
TI  - On: 'Projective transidentification'.

PMID- 16639849
TI  - On: Psychotherapy and psychoanalysis: a long and troubled relationship.

PMID- 16639850
TI  - Alcohol and suicidal behavior in adolescents: a medical and social problem.

PMID- 16639851
TI  - Functional magnetic resonance imaging in studies of neurocognitive effects of
      alcohol use on adolescents and young adults.
AB  - Alcohol use disorders (defined as alcohol abuse or dependence) are prevalent and
      serious problems among adolescents and young adults. Adolescence is a time of
      trying new experiences and activities that emphasize socializing with peers, and
      conforming to peer-group standards. These new activities may place young people
      at particular risk for initiating and continuing alcohol consumption. Exposing
      the brain to alcohol during adolescence may interrupt key processes of brain
      development, leading to cognitive impairment as well as to further escalation of
      alcohol use. Alcohol-induced adolescent learning impairments could affect
      academic and occupational achievements. Functional magnetic resonance imaging
      (fMRI) is a relatively new imaging technique that allows studying neurocognitive
      function. fMRI aims to determine the neurobiological correlate of behavior by
      identifying the brain regions that become active during the performance of
      specific tasks in vivo. The technique is non-invasive and relatively safe. This
      allows repeated studies to be carried out within a given subject. Several fMRI
      studies have been performed to evaluate neurocognitive function in adolescents
      and young adults with alcohol use disorders. Adolescents and young adults with
      alcohol use disorders had abnormalities in brain response to a working memory
      task. The results of the studies of cue reactivity and craving responses in young
      people suggest that the elevated physiological response and altered cognitive
      reactions to alcohol are involved in the pathogenesis of alcohol dependence in
      adolescents and young adults. Future fMRI studies may help ascertain the adverse
      affects of alcohol on brain function during early neurodevelopmental stages. fMRI
      may be uniquely powerful in the delineation of the underlying pathophysiology of
      alcohol use disorders in adolescents and young adults.

PMID- 16639852
TI  - Psychotherapy in the treatment of alcohol and substance abusing adolescents with
      suicidal behavior.
AB  - Adolescence is a unique time period in an individual's life, one in which suicide
      and substance abuse become substantial health risks. Currently, suicide accounts
      for approximately 14% of all deaths among 15-24 year olds in the U.S.A. Drug,
      alcohol abuse and dependence are the most prevalent causes of adolescent
      morbidity and mortality in the USA. Numerous studies have demonstrated the link
      between adolescent alcohol, substance abuse and suicide. When compared to
      community controls, the rate of a substance abuse disorder was 8.5 times higher
      in a sample of adolescent suicide completers and the rate of alcohol abuse was
      7.5 times higher. Genetic and biological variables may also be responsible for
      either alcohol and substance abuse or suicide or both alcohol and substance abuse
      and suicide. There is little empirical research evaluating the effectiveness of
      alcohol and substance abuse treatments for adolescents. Therapies such as
      multisystemic therapy, functional family therapy, motivational interviewing,
      community reinforcement, the 12-step approach and contingency management
      reinforcement seem to be effective treatments. Despite the strong association
      between adolescent alcohol and substance use and suicidal behaviors, few studies
      have investigated the combined treatment of these two issues. Cognitive
      behavioral therapy, particularly dialectical behavior therapy, seems to be a
      promising psychotherapy treatment for suicidality in alcohol and substance
      abusing adolescents. Further research is needed to determine the efficacy of
      various treatments of alcohol and substance abusing adolescents with suicidal
      behavior.

PMID- 16639853
TI  - Impulsive-aggressive traits and suicidal adolescents and young adults with
      alcoholism.
AB  - Suicidal behavior and alcohol use disorders among adolescents and young adults
      are serious public health problems. In the study of suicidal behavior among young
      people with alcoholism, it has been shown that aggression and impulsivity are
      higher among those who attempted suicide. Impulsivity has been related to
      suicidal and self-destructive behaviors within different psychiatric conditions,
      i.e. alcohol and substance use disorders, mood disorders, conduct disorder,
      impulse control disorders, antisocial personality disorder, and borderline
      personality disorder. The term impulsivity has been used to define different
      constructs such as (1) personality trait or cognitive style in which
      disinhibition is the core characteristic, (2) a tendency to act immediately in
      response to external or internal stimuli, and (3) a group of psychiatric
      disorders with behavioral dyscontrol. Among adolescents suicidal behavior is
      transmitted in families independently of psychiatric conditions, but not
      independently of impulsivity/aggression. Two causal links between impulsiveness
      and alcoholism have been proposed: (1) adolescents who develop alcoholism possess
      higher premorbid levels of impulsiveness than those who do not develop
      alcoholism, and (2) levels of impulsiveness differentiate both populations only
      after the development of alcoholism, with higher levels of impulsiveness among
      those adolescents who developed alcoholism. Cognitive behavioral techniques have
      shown promising results in the treatment of adolescents with alcohol and
      substance use disorder and suicidality. The relative frequency of suicidal
      behavior among adolescents and young adults suffering from alcoholism and its
      subsequent devastating effects on individuals, families and society merits
      further research and development of prevention strategies.

PMID- 16639854
TI  - The constitutionality of random drug and alcohol testing of students in secondary
      schools.
AB  - Adolescent drug and alcohol use is a major public health problem. Multiple
      studies indicate that substance use is a risk factor for physical and mental
      disorders in adolescents. Secondary schools and the communities they serve have
      been facing a long-standing problem of substance abuse. American adolescents have
      become quite accustomed to drug prevention being a part of their curriculum.
      However, some policy decisions made by school administrators have been legally
      challenged. In 1989, Vernonia School District serving a small community in
      Oregon, instituted a random drug testing policy of its athletes. In 1991, the
      parents of a seventh grader refused to give their consent for random drug
      testing. The seventh grader was denied participation in the sport and sued the
      School District arguing that the school policy violated the Fourth and Fourteenth
      Amendments to the United States Constitution, and Article I, Section 9 of the
      Oregon Constitution. In 1995, on appeal to the Supreme Court of the United
      States, the School District won the case. The Vernonia School District versus
      Acton case became a landmark case, but random drug and alcohol testing in
      secondary schools has been a subject of multiple court cases. The authors discuss
      three of them. Both Federal and State Courts have recognized that a secondary
      school environment in itself represents "a special need," for which suspicionless
      searches are sometimes necessary to maintain order, safety, and discipline. Drug
      and alcohol testing programs in secondary schools may still be challenged on its
      legality. Therefore, examining court sanctioned programs and their long-term
      efficacy statistics is recommended.

PMID- 16639855
TI  - Stigma and alcohol misuse during adolescence.
AB  - Stigma associated with alcohol misuse can have serious consequences for
      adolescents, who may be at risk of developing abuse and dependence disorders.
      Adolescence is a period that involves wide use of psychoactive substances. During
      this developmental phase, adolescents are strongly influenced by peer group
      norms, which do not necessarily stigmatize alcohol use. Unintentionally, a
      significant subgroup of adolescents may develop problems that are a result of
      alcohol misuse. The stigma about alcohol problems may keep adolescents from
      admitting that their difficulties are exacerbated by misuse of alcohol. When
      their behavior crosses the line from norm to inappropriate, the label of
      alcoholic may be applied and the stigma that is attached to the label will have
      additional consequences. This includes withdrawal of social supports and even
      access to treatment. Adolescents with alcohol use problems may be reluctant to
      identify themselves with these difficulties, because of their concern about being
      rejected. These adolescents may present with emotional or behavioral problems,
      rather than alcohol concerns. Clinicians may avoid inquiring about alcohol use,
      because of their own negative and pessimistic perceptions of this disorder.
      Clinicians can be important resources for these adolescents, but this requires
      that clinicians examine their own prejudgments about alcohol abuse and
      dependence. This can facilitate meaningful inquiry about alcohol use and begin to
      offset the stigma and negative self-worth of these adolescents.

PMID- 16639856
TI  - Alcohol use in adolescents with eating disorders.
AB  - Eating disorders, in particular bulimia nervosa and binge eating disorder are
      associated with co-morbid alcohol and drug abuse. School-based studies have shown
      significant associations between bulimic behaviors and various measures of
      alcohol, cigarette and other drug use and abuse. Amongst bulimic adolescents,
      substance use is related to an increased likeliness of high risk behaviors such
      as attempted suicide, stealing and sexual intercourse. In contrast with bulimics
      and binge eaters, restricting anorexics have low rates of co-morbid substance
      abuse. It appears that restricting anorexics, binge eaters and bulimics represent
      distinct subgroups within the eating disordered population and binge eaters and
      bulimics are more prone to alcohol use. It is possible that individuals with
      eating disorders turn to alcohol use/abuse as a way of coping with the problems
      caused by their eating disorder. Researchers have proposed that an addictive
      personality is an underlying trait, which predisposes individuals to both eating
      disorders and alcohol abuse. Eating disorders are often conceptualized as an
      addictive disorder. Opioid antagonists, such as naltrexone, may be useful in
      treating both eating and alcohol use disorders. There is also evidence that
      serotonin reuptake inhibitors, which are traditionally used to treat major
      depression, may be an effective treatment. Cognitive-behavioral therapy has been
      effective in treating alcohol use and eating disorders individually and may be an
      effective combined treatment for co-morbid eating disorders and alcohol use.
      Teaching healthy ways to cope with the stressful situations may also help
      decrease alcohol use and disordered eating behaviors.

PMID- 16639857
TI  - Pathways for practice and policy to reduce adolescent alcohol abuse:
      interpretations from a qualitative study.
AB  - This paper highlights pathways for practice and policy to reduce alcohol abuse
      among adolescents aged 14-17 years. These pathways have been generated following
      a qualitative study in England that explored adolescents' motivations for binge
      drinking and the associated outcomes. There are three distinct pathways under
      consideration. Firstly, the research clearly evidences the close link between
      binge drinking and an array of risky outcomes, thus supporting policies that
      tackle generic risk taking (such as Youth Development Programmes). Secondly,
      given the widely reported positive motivations for binge drinking, adopting a
      harm-minimisation approach may be more appropriate than promoting abstinence.
      This harm-minimisation approach can build on strategies reported by adolescents
      (such as drinking in groups) and consider safer, more supervised venues for
      adolescent drinking. Thirdly, this study highlights key risk groups, which would
      arguably be in greater need of harm-minimisation strategies. These were
      adolescents who drank primarily for the 'buzz', and also those younger age groups
      (particularly 14 and 15-year-olds) whose drinking was mostly confined to
      unsupervised, often outdoor locations. This was in contrast to slightly older age
      groups who, although illegally, were often able to access licensed premises which
      exerted more control over their drinking. The paper closes by referencing some of
      the wider policy issues, which must be taken into consideration when attempting
      to change the culture of binge drinking in England. These include issues
      surrounding the advertising and marketing of alcohol, the provision of alcohol
      education in schools and the promotion of alternative, safer activities for
      adolescents.

PMID- 16639858
TI  - Family-based treatment development for adolescent alcohol abuse.
AB  - A range of family-related risk factors have been linked to adolescent alcohol
      problems and predict escalation of use and alcohol dependence into adulthood.
      Family-based interventions have strong research and clinical traditions in the
      treatment of adult alcoholism and adolescent drug abuse, but have been
      infrequently applied to the unique problems of adolescent alcohol abuse and
      dependence. Researchers in the adolescent alcohol abuse specialty area have
      developed a robust developmentally oriented knowledge base about alcohol-specific
      risk and protective factors. Adolescent alcohol treatment researchers have made
      significant advances in recent years, including a deeper understanding of outcome
      trajectories. However youth relapse to alcohol use at high rates following
      standard community-based treatment, and few empirically supported treatments
      exist for adolescent alcohol abusers. Employing selected contemporary research
      findings, this article outlines specific areas of focus for a family-based
      intervention for alcohol abusing teens. We first review intervention-relevant
      research on the development of alcohol problems among adolescents with a focus on
      family risk and protective factors. Second, clinical research findings are
      presented supporting the use of family-based interventions with alcohol abusing
      youth. Finally, areas of intended focus in an empirically supported family-based
      intervention for adolescent alcohol problems are outlined. By addressing these
      gaps, empirically supported family-based interventions for adolescent alcohol
      abuse have significant potential to advance the field of adolescent alcohol
      treatment.

PMID- 16639859
TI  - Motivational interviewing with adolescents and young adults for drug-related
      problems.
AB  - This article reviews studies of brief motivational interviewing (MI)
      interventions applied to adolescents (ages 13 to 18 years) and young adults (ages
      19 to 25 years) using alcohol or other psychoactive substances. An overview of
      the principles of MI is provided followed by a review of 17 clinical studies
      reported in the literature. This review revealed mixed findings for the efficacy
      of brief MI among these populations. However, in 29% of the studies (5 of 17),
      there was a clear advantage of the brief MI demonstrated compared to standard
      care or other programming. Components common to successful brief MI interventions
      included one-on-one sessions and feedback on substance use compared to norms.
      Interviewer empathy has been shown to be a key component in studies with adults,
      but this was not measured in a standardized manner across the current studies.
      The studies reviewed here indicate that brief MI might be effective among these
      populations, but the key components necessary for successful MI interventions
      have not been fully identified.

PMID- 16639860
TI  - Alcohol use and abuse amongst adolescents in Hong Kong.
AB  - This paper discusses alcohol use and abuse amongst adolescents in Hong Kong on
      the basis of a thorough literature review of official statistics and empirical
      research. The review highlights four major observations. Firstly, the alcohol
      culture of Hong Kong adolescents is basically positive and social-oriented. The
      existing legal constraint on the use of alcohol by those aged under 18 seems to
      exist in name only. Secondly, the past decade has seen a rising trend in alcohol
      use by adolescents, both in terms of those who have ever consumed it and those
      who do so currently. Thirdly, several demographic variables associated with
      alcohol use have been identified, including gender, age, and school mode.
      Fourthly, peer interactions (such as involvement in organized criminal groups)
      and family factors (such as lack of maternal support) are also related to alcohol
      use in young people. The paper closes by making some observations on the gaps in
      the research and sets forth some ideas for future policy development.

PMID- 16639861
TI  - The relationship between the frequency of alcohol use and suicide rates in young
      people.
AB  - BACKGROUND: Suicide is an important public health problem and one of the leading
      causes of death among adolescents. In the United States, the death rate from
      suicide amongst 15-19 year olds doubled between 1960 and 2001. It has been
      suggested that alcohol misuse contributed to this increase in suicide rates among
      young people. We examined the relationship between the percentage of frequently
      drinking high school students and suicide rates among 15-24 year olds in 17
      countries. METHODS: Correlations were computed to examine the relationship
      between suicide rates in 15-24 year old males and females and the percentage of
      frequently drinking students in 17 countries. Using median split, countries were
      divided into two groups according to the percentage of frequently drinking
      students. Suicide rates in countries with the lower percentage of frequently
      drinking students were compared to suicide rates in countries with the higher
      percentage of frequently drinking students using t-test. RESULTS: There was a
      negative correlation between the percentage of frequently drinking students and
      suicide rates in both males (n=17, r = -0.51, p = 0.037) and females (n=17, r = 
      0.55, p = 0.023). The countries with the lower percentage of frequently drinking
      students had higher suicide rates in both 15-24 year old males (t = 2.25, df=15,
      p = 0.005) and females (t = 4.03, n=15, p = 0.001). CONCLUSION: Suicide rates
      among 15-24 year old males and females were lower in the countries with the
      higher percentage of frequently drinking high school students. Our finding is
      consistent with the suggestion that "alcoholism tends to protect one against
      suicide early on, but after 20-25 years (if not earlier) it exacerbates suicide
      potential" (Maris, 1992). The results of this study should be treated with
      caution until replicated.

PMID- 16639862
TI  - Demographic and clinical features of adolescents and young adults with alcohol
      related disorders admitted to the psychiatric emergency room.
AB  - OBJECTIVES: To determine the incidence of alcohol related problems (ARP) among
      adolescents admitted to the Psychiatric Emergency Room (PER) and to describe the
      demographic and clinical characteristics. METHODS: The study was a retrospective
      review of admissions to the PER, where we reviewed the psychiatric records of all
      of the 14-30 year olds admitted to the PER during the three-month period between
      April 1st, 2003 and June 30th, 2003. Demographic and clinical data of subjects
      with and without ARP were compared. RESULTS: During the three-month time period,
      108 patients between the age of 14 and 30 were admitted to the PER. 14 (13.2%) of
      these had ARP, and ARP tended to occur more in males (chi2 = 3.81; df=l; p =
      0.05). The number of psychiatric diagnoses among those who had ARP was
      significantly higher than among those who did not have ARP (t = -3.12; df=104; p
      = 0.002). ARP were found to be associated with personality disorder and misuse of
      other substances. 37.5% of those adolescents and young adults with ARP had a
      personality disorder, while 13% of those without ARP had a personality disorder
      (chi2 = 4.64; df=1; p = 0.03). 50% of those with ARP consumed (an)other
      substance/s, while 12.0% of those patients without ARP consumed (an)other
      substance/s (chi2 = l2.48; df=1; p < 0.001). Of the female adolescents and young
      adults with ARP, 50% were admitted to PER after an episode of self-poisoning.
      CONCLUSION: ARP in young adults admitted to the PER for acute psychiatric care
      are associated with greater psychiatric comorbidity, especially personality
      disorders. In females, ARP may be associated with an increased risk for self
      poisoning. Adequate detection of ARP in the PER could promote earlier specific
      interventions specifically tailored to ARP among adolescents and young adults.

PMID- 16639863
TI  - Social competence among urban minority youth entering middle school:
      relationships with alcohol use and antisocial behaviors.
AB  - Social competence is increasingly multidimensional during adolescence as young
      people encounter a variety of new social situations and can respond with a broad
      range of appropriate behaviors. However, research on social competence has
      focused more on children than adolescents. The present study examined the
      relationships between components of social competence (e.g., assertiveness and
      social confidence) and adolescent problem behaviors including alcohol use and
      antisocial behaviors (e.g., aggression and delinquency). A survey was
      administered to 6th grade students (N=2411) entering 20 New York City public and
      parochial middle schools and again a year later in the 7th grade. Findings
      indicated that verbal aggression was reported most frequently among students
      (93%), followed by physical aggression (69%), delinquent behaviors (53%), and
      alcohol use (16%). Structural equation modeling indicated that while
      assertiveness was protective in terms of adolescent problem behaviors, social
      confidence--the level of confidence that students had in initiating social
      interactions including dating--was associated with greater alcohol use and
      antisocial behavior both cross-sectionally and longitudinally. Additional
      analyses revealed that social confidence related to the initiation of dating
      (e.g., asking someone out for a date or having a conversation with a member of
      the opposite sex) was most strongly correlated with each problem behavior
      outcome. These findings suggest that social confidence, particularly as it
      relates to precocious dating behavior during early adolescence, is a risk factor
      for the early initiation of alcohol use and antisocial behavior.

PMID- 16639864
TI  - Television and music video exposure and adolescent 'alcopop' use.
AB  - Alcohol abuse among adolescents is a cause for concern. Around 1995 alcopops
      (sweetened alcoholic drinks) entered the scene and caused even more concern. Many
      fear that the sweet taste makes is easier to start drinking for those not yet
      used to drinking alcohol and the marketing appears aimed at adolescents. Because
      alcohol use has been linked to television viewing in general and music video
      viewing in particular this article examined whether a relationship existed
      between television and music video exposure and the consumption of alcopops. Data
      were collected with a questionnaire focused on television exposure and alcohol
      behavior. Respondents were a random sample of 2,546 first- and fourth year
      schoolchildren of Flanders, the Dutch speaking region of Belgium (60% of the
      Belgian population). Self reported general TV viewing, music video exposure and
      drinking of alcopops at home and/or while going out were measured. 68.4% of the
      respondents watched music videos at least several times a week. The odds of being
      an alcopop drinker at home increased by 196% for those, who watched music videos
      at least several times a week (OR = 1.961). For each additional hour of TV viewed
      per day, the respondents were 17% more likely to be drinkers of altopops at home
      (OR = 1.169). The odds of being an alcopop drinker, when going out increased by
      239% for those who watched music videos at least several times a week (OR =
      2.394). For each additional hour of TV viewed per day, the respondents were 19%
      more likely to be drinkers of alcopops when going out (OR = 1.186). These
      findings suggest that there is an association between music video exposure and
      use of alcopops not explained by overall exposure to television. This
      relationship merits further attention as it is a better predictor of alcopop use,
      than the control variables and overall TV viewing.

PMID- 16639865
TI  - Utility of the AUDIT for screening adolescents for problematic alcohol use in the
      emergency department.
AB  - The emergency department is a setting conducive to screening adolescents for
      problematic alcohol use, who can then be targeted for further evaluation and
      intervention. This study examined the utility of the Alcohol Use Disorders
      Identification Test (AUDIT) as a screening measure for identifying young
      adolescents in an urban emergency department (ED). Adolescents (13-17 years old)
      who presented to the ED were screened as part of a larger study. A total of 859
      adolescents, who denied alcohol use prior to their ED visit were administered the
      AUDIT. Of the 500 younger adolescents (13-15 years old), approximately 4% (n=22)
      were classified as AUDIT-positive using a cut-score of four or greater. Of the
      359 older adolescents (16-17 years old), almost 19% (n=67) were classified as
      AUDIT-positive. The ability of shorter versions of the AUDIT to identify AUDIT
      positive adolescents (as classified by the 10-item AUDIT using a cut-score of
      four or greater) was also explored. Since the adolescents in the current study
      were not alcohol-positive at the time of the ED visit, they would likely have
      been missed by biochemical alcohol screening alone. Screening procedures that
      employ the AUDIT may be most efficient when adapted for the specific adolescent
      age group (younger versus older), thus identifying the highest number of
      adolescents who should be targeted for intervention. Lowering the recommended
      adult cut-scores on the shorter versions of the AUDIT appears necessary to
      identify adolescents who may benefit from intervention or referral.

PMID- 16639866
TI  - Entertainment and music magazine reading and binge drinking among a group of
      juvenile offenders.
AB  - This study examines the relative contribution of exposure to entertainment and
      music magazines on binge drinking among a group of teenagers under the
      supervision of a juvenile court system in a medium-sized western United States
      community. Despite having a large proportion of adolescent readers, entertainment
      and music magazines typically include a substantial number of advertisements for
      alcoholic beverages in each issue. Data were collected via a self-report
      questionnaire administered to 342 juvenile offenders (ages 12-18 years). Three
      quarters of our respondents reported they have used alcohol and about 37%
      indicated they were binge drinkers. As anticipated, binge drinkers were more
      frequent readers of entertainment and music magazines than non-binge drinkers.
      Binge drinkers also estimated that larger portions of their classmates used
      alcohol and would be more accepting of regular drinking than non-binge drinkers.
      Results of a multivariate logistic regression analysis to predict whether our
      subjects typically consumed five or more drinks during a drinking episode
      indicated that perceived ease of access, age, gender, the number of best friends
      who drink, parental drinking (inversely), and entertainment and music magazine
      reading frequency were significant predictors of binge drinking. We conclude that
      the predictive influence entertainment and music magazine reading frequency may
      actually reflect a selectivity bias among a segment of the youth sub-culture
      already inclined toward alcohol use and abuse. We recommend that entertainment
      and music magazine reading should be considered only within the constellation of
      other risk factors when assessing risk for potential alcohol abuse.

PMID- 16639867
TI  - Modified dexamethasone suppression-corticotropin-releasing hormone stimulation
      test: A pilot study of young healthy volunteers and implications for alcoholism
      research in adolescents and young adults.
AB  - The key neuroendocrine component of a response to stress is the hypothalamic
      pituitary-adrenocortical (HPA) system. Abnormalities in the HPA system have been
      implicated in the pathophysiology of psychiatric disorders such as depression,
      post-traumatic stress disorder, alcoholism and suicide. The dexamethasone
      suppression test (DST) is the most frequently used test to assess HPA-system
      function in psychiatric disorders. This neuroendocrine test consists of the
      administration of a low dose of dexamethasone at 11 pm and the measurement of
      cortisol levels at one or more time points on the following day. After
      corticotropin-releasing hormone (CRH) became available for clinical studies, the
      DST was combined with CRH administration. In this test, patients are pretreated
      with a single dose of dexamethasone at 11 pm and receive human CRH intravenously
      at 3 pm the following day. The resulting DST-CRH test proved to be much more
      sensitive in detecting HPA system alterations than the DST. We have modified the
      DST-CRH test and used ovine CRH instead of human CRH in a pilot study of a group
      of young healthy volunteers. Results indicated that it produces results similar
      to the results obtained with human CRH. This suggests that ovine CRH can be used
      in psychiatric research. Alcoholism is associated with abnormalities in HPA
      function. Nonalcoholic subjects with a family history of alcoholism exhibit lower
      plasma ACTH and beta-endorphin as well as lower ACTH, cortisol, and beta
      endorphin responses to psychological stress and CRH stimulation. This suggests
      that in children of alcoholics, alterations in the mechanisms that regulate HPA
      axis activity predate the development of alcohol dependence and may be considered
      inherited traits. Therefore, studies of the HPA system in persons at risk for
      alcoholism may help understand the neurobiological mechanisms of predisposition
      to alcoholism.

PMID- 16639868
TI  - Effects of naltrexone on the acquisition of alcohol intake in male and female
      periadolescent and adult alcohol-preferring (P) rats.
AB  - The objective of this study was to compare the effects of naltrexone (NTX) on the
      acquisition of alcohol drinking, during periadolescence and adulthood in rats
      using a rodent model of alcoholism. Periadolescent and adult alcohol-preferring
      (P) rats of both sexes were given access to water and 15% (v/v) alcohol 24-hr/day
      for 45 days. Alcohol access started at 1200 hr on post-natal day (PND) 30 for the
      periadolescent rats and approximately PND 90 for the adult rats. Subcutaneous
      (SC) injections of NTX (0, 5, 10, 20, and 30 mg/kg) were administered daily
      between 1600-1700 hr to separate groups of animals during the first 10 days of
      alcohol access. During the treatment period, differential effects on alcohol
      intake were seen between periadolescent and adult animals: (a) lower doses of NTX
      were more effective in the periadolescent than the adult P rats, and (b) greater
      tolerance to repeated dosing was displayed by adult, compared with
      periadolescent, rats. By the 20h day of alcohol access there were no significant
      differences between the NTX dose groups. Additionally, there were no sex of
      animal differences at the ages tested. These findings indicate that the
      endogenous opioid system(s) mediating alcohol intake are developmentally present
      in periadolescent P rats, such that NTX not only interfered with the acquisition
      of alcohol intake by adolescent P rats but appeared to also have a greater effect
      than that observed in adult P rats. Therefore, NTX may serve as an effective
      treatment in reducing alcohol abuse and dependence in genetically, and perhaps
      environmentally, at-risk youth.

PMID- 16639869
TI  - Cardiovascular risk factors in adolescents with alcohol use disorders.
AB  - Among adults, chronic alcohol dependence is associated with cardiovascular
      disease (CVD). While it is unlikely that adolescents with alcohol use disorders
      (AUDs) would exhibit CVD, they might show elevated CVD risk factors. The purpose
      of this study was to compare CVD risk factors in adolescents with AUDs and an
      adolescent reference group. Adolescents with AUDs were recruited from treatment
      sources and reference adolescents were recruited from the community. Information
      about smoking behavior, exercise, and diet were gathered from interview and self
      report measures. Body mass index and blood pressure were determined by physical
      exam and a blood sample was drawn to measure serum cholesterol and triglycerides.
      Compared with the reference group, adolescents with AUDs reported significantly
      more smoking, were less likely to report exercising regularly, and were less
      likely to report eating a balanced diet. Adolescents with AUDs were not more
      likely to be overweight or to exhibit hypertension, and lipid levels were also
      not significantly elevated. These results indicated that adolescents with AUDs
      endorsed problematic health behaviors while not yet exhibiting the consequences
      of these behaviors. Interventions focusing on health behaviors in conjunction
      with addiction treatment might help improve long-term health outcomes in
      adolescents with AUDs.

PMID- 16639870
TI  - Heavy drinking and patterns of sociability at the end of adolescence: a French
      survey.
AB  - Many alcohol-related problems at adolescence occur during or as a result of peer
      oriented activities, so it is necessary to understand how drinking habits are
      embedded in sociability and lifestyle. OBJECTIVE: to study patterns of peer
      oriented activities among heavy drinkers, and to investigate factors associated
      with these patterns. STUDY GROUP: A national random sample of 13,623 French
      adolescents aged 17-18 years, and a subgroup of 762 heavy drinkers (reporting
      either 20 drinking occasions or more during the prior 30 days, or 20 episodes of
      drunkenness or more during the previous 12 months). METHODS: Respondents answered
      to a self-administered closed-ended questionnaire. Questions on peer-oriented
      activities were used for conducting a cluster analysis among heavy drinkers.
      Logistic regressions were used for studying factors associated with the resulting
      clusters. RESULTS: Among heavy drinkers the dominant pattern was characterized by
      the combination of heavy drinking and peer-oriented activities. But in two other
      profiles heavy drinking was associated with either strong involvement in formal
      sporting practice or low participation in peer-oriented activities. The expected
      relationship between heavy drinking, mood disorders, other drug use, violence and
      victimization depended on which pattern was considered. CONCLUSIONS: The strong
      links observed between drinking habits and sociability underline the need to
      counteract the social acceptability of drinking and focus on the social contexts
      in which it occurs, but preventive action programs should also take into account
      the diversity of sociability patterns among heavy drinkers.

PMID- 16639871
TI  - Transition to college: A classification and regression tree (CART) analysis of
      natural reduction of binge drinking.
AB  - Approximately one in five teens that drank heavily in high school reduces or
      discontinues consumption while in college. Multiple paths might lead to the
      common outcome of natural reduction in heavy drinking. Statistical modeling of
      this complex process of natural reduction is a challenge with standard linear
      statistics. The purpose of this paper is to use a new statistical procedure,
      Classification and Regression Tree (CART), to model the equifinality of reduction
      in drinking by college students who drank heavily as adolescents. An appealing
      aspect of CART is that the resulting tree model that can easily be interpreted
      and applied by those who work with adolescents during the important transition
      from high school to college. Of 201 college students who first binged on alcohol
      while in high school, 71 (35.3%) denied heavy or binge drinking within the
      previous three months (Natural Reducers). The final model accurately classified
      84.6% of the students as either continued heavy drinkers or natural reducers.
      Sensitivity was modest (accurate identification of 67.6% of the reducers);
      however, specificity was strong (correct classification of 93.8% of the continued
      heavy drinkers). The model revealed four pathways to natural reduction in
      drinking. Predominant in each path was the influence of social factors that
      maintain continued drinking (e.g., social facilitation outcome expectancies,
      perception of friends' drinking) or facilitate natural reduction (e.g., regular
      church attendance). The results support the application of CART to model health
      behaviors across the transition from adolescence to young adulthood.

PMID- 16639872
TI  - Alcohol use frequency as a screen for alcohol use disorders in adolescents.
AB  - While screening tools have been developed to identify adolescents likely to have
      alcohol use disorders (AUDs), none of the available methods are optimal for
      general medical settings. This study explored the sensitivity and specificity of
      the frequency of drinking episodes in the prior month as an initial screen for
      AUDs. The subjects were 219 adolescents (ages 12 through 18) systematically
      recruited from the community, who participated in a baseline assessment as well
      as 1-year, 3-year, and 5-year follow-up visits. Subjects completed a self-report
      form indicating their frequency of use of different substances in the month prior
      to the assessment. DSM-IV AUD diagnoses were determined by SCID. At baseline, 10
      of 219 subjects met DSM-IV criteria for an AUD. At a threshold of 3 or more
      drinking episodes in the past month, the screen was 90% sensitive, correctly
      classifying 9 of 10 AUD cases, and 83.7% specific, correctly classifying 175 of
      209 cases without AUDs. The diminishing specificity of this screen over the
      follow-up assessments indicated that this method may be useful for adolescents,
      but not for young adults. These results indicate that an assessment of the
      frequency of alcohol use in the prior month provides an initial screen with
      acceptable sensitivity and specificity for use with adolescents.

PMID- 16639873
TI  - Impulsivity, suicidality and alcohol use disorders in adolescents and young
      adults with borderline personality disorder.
AB  - Borderline Personality Disorder (BPD) is a severe and disabling psychiatric
      condition that typically emerges in late adolescence or early adulthood. Nearly
      50% of individuals with BPD have a co-occurring Alcohol Use Disorder (AUD) at
      some point in the course of their illness. This study explores clinical
      characteristics of adolescents and young adults (age 30 years and younger) with
      BPD and AUD (N=21) compared to BPD without any history of substance use disorders
      (N=17). Based on theoretical considerations and previous findings, we
      hypothesized that adolescents and young adults with BPD and AUDs would be more
      impulsive and exhibit higher rates of suicidal behavior than individuals with BPD
      and no substance use disorders. Consistent with our first hypothesis, the BPD/AUD
      group was more impulsive than the BPD only group. However, the two groups did not
      differ on measures of suicidal behavior. Overall, impulsivity was correlated with
      total number of suicide attempts in the adolescent/young adult group. When older
      BPD participants were included in the comparison (up to age 55), the BPD/AUD
      group exhibited more lifetime suicide attempts that were higher in medical
      lethality than the BPD only group, suggesting an overall increased lifetime
      suicide risk in the BPD/AUD group. The relationship between impulsivity, AUD, and
      suicidal behavior and lifetime suicide risk in adolescent and young adults with
      BPD is discussed.

PMID- 16639874
TI  - Prevalence of alcohol misuse among adolescents and young adults evaluated in a
      primary care setting.
AB  - OBJECTIVE: To determine the prevalence of alcohol misuse among older adolescents
      and young adults evaluated in a primary care setting using the CAGE
      questionnaire. METHODS: In this crossover descriptive study, a general
      practitioner, using the CAGE questionnaire, interviewed consecutive primary care
      patients aged 18-30 years. RESULTS: 29.5% of adolescents and young adults
      answered "yes" to at least one question of the CAGE questionnaire. However, only
      7.4% of study participants gave an affirmative answer to at least two CAGE
      questions. There were more males than females among subjects who answered "yes"
      to at least one question. Furthermore, males more commonly gave an affirmative
      answer to at least two CAGE questions. CONCLUSIONS: A substantial number of older
      adolescents and young adults evaluated at a primary care center may have alcohol
      misuse. Instruments with higher sensitivity may be preferable in screening
      procedures for alcohol misuse. Responses suggestive of problematic drinking
      should be confirmed during the second post-screening stage with a more detailed
      discussion about patterns of use, problems related to drinking, and symptoms of
      alcohol use disorder. Further studies of prevention interventions in adolescents
      and young adults are needed.

PMID- 16639875
TI  - Insecure attachment and college-age alcohol use disorders. A case report.
AB  - Teens and young adults with insecure attachment may be remarkably susceptible to
      alcohol and substance use disorders. Particularly in the separation process of
      leaving-home and entering college, an underlying insecure attachment may manifest
      through symptoms of alcohol or drug abuse; as these young adults engage in what
      is perceived to be adult drinking behavior, they become too "attached" to the
      alcohol as a substitute for earlier, sporadically-available objects (usually
      parents). That is, they enact a similar relationship to this drug that they may
      have learned to have with an insecure parent: too close at times, but ultimately
      fostering guilt, dependence and destructive action. Fear of abandonment,
      rejection and negative judgment may be intensified in this age group as they
      struggle at the cusp of independence, but these issues are particularly relevant
      for insecurely attached teens. In this report, attachment theory is briefly
      described and applied to the assessment and treatment of a college freshman
      diagnosed with an alcohol use disorder. By engaging the patient in evaluating her
      actions and motives through the attachment model, the therapy helps her to
      channel help-seeking behavior appropriately, to establish expectations for
      consistency and reliability from significant people in her life and to feel safer
      without turning to alcohol as a crutch. An argument is made for the general
      application of attachment theory to alcohol and drug use disorders in this
      significant phase of young adult development.

PMID- 16639876
TI  - Modulatory effect of fish oil on the myocardial antioxidant defense system in
      isoproterenol-induced myocardial infarction.
AB  - The effect of fish oil treatment on the activities of antioxidants such as
      superoxide dismutase, catalase, glutathione peroxidase, glutathione-s
      transferase, and glutathione, as well as the level of the lipid peroxidation
      marker thiobarbituric reactive substance was studied in isoproterenol-induced
      myocardial infarction (MI). To confirm the induction of MI by isoproterenol, we
      studied the activities of cardiac marker enzymes like creatinine kinase and
      lactate dehydrogenase and the level of troponin. The biochemical lesions due to
      the activation of lipid peroxidation and decrease in antioxidant status are
      significantly implicated in experimental isoproterenol-induced MI. The results
      indicate that the protective effect of fish oil is achieved by decreasing the
      peroxide concentration and normalizing antioxidant defense enzymes.

PMID- 16639877
TI  - Combined n-benzoyl-d-phenylalanine and metformin treatment reverses changes in
      the fatty acid composition of streptozotocin diabetic rats.
AB  - The present investigation was carried out to evaluate the effect of N-benzoyl-D
      phenylalanine (NBDP) and metformin on blood glucose, plasma insulin, and on the
      fatty acid composition of total lipids in the livers and kidneys of control and
      experimental diabetic rats. When compared with nondiabetic control rats, neonatal
      streptozotocin (nSTZ) diabetic rats showed a significant increase in blood
      glucose and decreased plasma insulin. Analysis of fatty acids revealed a
      significant increase in the concentration of palmitic, stearic, and oleic acids
      in liver and kidney, whereas linolenic and arachidonic acids were significantly
      decreased. In diabetic rats, the oral administration of combined NBDP/metformin
      for 6 wk decreased the high concentrations of palmitic, stearic, and oleic acids
      and elevated the low levels of linolenic and arachidonic acids. The results
      suggest that the NBDP/metformin combination exhibits both antidiabetic and
      antihyperlipidemic effects in nSTZ diabetic rats and prevents the fatty acid
      changes produced during diabetes.

PMID- 16639878
TI  - Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles
      and liver histopathology in rats.
AB  - Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate
      cholesterol metabolism. We studied the effect of the simultaneous oral treatment
      with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100
      g BW, i.p) on nickelinduced changes in serum lipid profiles and liver
      histopathology. Nickel-treated rats showed a significant increase in serum low
      density lipoprotein-cholesterol, total cholesterol, triglycerides, and a
      significant decrease in serum high-density lipoprotein-cholesterol. In the liver,
      nickel sulfate caused a loss of normal architecture, fatty changes, extensive
      vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy.
      Simultaneous administration of L-ascorbic acid with nickel sulfate improved both
      the lipid profile and liver impairments when compared with rats receiving nickel
      sulfate only. The results indicate that L-ascorbic acid is beneficial in
      preventing nickel-induced lipid alterations and hepatocellular damage.

PMID- 16639879
TI  - Neutrons and sudden cardiac death (SCD) codes 121-125 ICD 10.
AB  - Recent studies have shown that (1) monthly neutron activity (NA) (imp/min)
      correlates with monthly number of acute myocardial infarction (AMI); (2) NA is
      higher on days of automatic implantable cardioverter defibrillators (AICD)
      discharges for VT, VF. Here we checked the level of NA in relation to timing and
      type of sudden cardiac death (SCD) patients [n=848 (579, 68.28% male)] obtained
      from the Kaunas registry for the years 2002-2004. All underwent Forensic Medicine
      post mortem examination and classification according to ICD10 by code 121-125.
      Daily NA data were obtained from Oulu U-ty, Finland and Moscow Monitoring Station
      of the Russian Academy of Sciences. No difference in NA was found on days with or
      without SCD. In men < 65, SCD occurred on days with higher NA than in women of
      the same age (p = 0.01) or in > 65 y old men (p = 0.045). Days of SCD with
      myocardial ruptures showed the highest level of NA, significantly higher than on
      all days (n = 669) of SCD (p = 0.037) and all 1096 days of the study (p =
      0.0048). Three groups were accompanied by significantly higher NA: repeated AMI,
      myocardial ruptures (codes122, 123), and coronary atherothrombosis without AMI,
      related to electrical heart instability. The mechanism of possible neutron role
      in pathophysiology needs special studies.

PMID- 16639880
TI  - Are neutrons involved in the pathogenesis of life-threatening cardiac
      arrhythmias?
AB  - Geomagnetic fields protect the earth from the adverse effects of cosmic rays,
      whose activity can be indirectly measured by monitoring the level of neutrons in
      the environment. The number and days of discharges from automatic implantable
      cardioverter defibrillators (ICD) in patients with cardiac arrhythmias are
      inversely correlated with the daily level of geomagnetic activity (GMA). The aim
      of the present was to determine whether neutron levels on days of AICD discharges
      are higher than average. Days on which discharges occurred were recorded in 31
      patients bearing ICDs for managing ischemic cardiomyopathy. Daily neutron levels
      obtained from the monitoring data of the Russian Academy of Sciences in Moscow
      were analyzed using Student's t test. The mean (+/-SD) daily neutron level for
      the 1096-day period was 8299.29 +/- 294.236 imp/min (median 8252), and for days
      of ACID discharge, 8423.93 +/- 274.187 imp/min (median 8443) (p = 0.0002). The
      mean neutron activity on days of AICD discharges in response to ventricular
      disturbances was significantly higher than the mean level over the 1096-day study
      period. Whether this relation is a direct result of low GMA or due to an
      independent role of neutrons in the pathogenesis and timing of cardiac
      arrhythmias is unknown.

PMID- 16639881
TI  - Changes in nitrogen metabolism of the freshwater fish Cirrhinus mrigala following
      exposure to cypermethrin.
AB  - We studied the effect of a synthetic pyrethroid insecticide, cypermethrin, on
      some aspects of nitrogen metabolism in the gills, liver, and muscle tissue of the
      Indian major carp, Cirrhinus mrigala. Free amino acid levels and protease
      activity showed an elevation in all tissues following exposure to lethal (5.13
      microg/L) and sublethal (1.026 microg/L) doses of cypermethrin, with significant
      changes noticed on day 4. The normal condition was restored only at a sublethal
      concentration.

PMID- 16639882
TI  - A decision-making framework for sediment contamination.
AB  - A decision-making framework for determining whether or not contaminated sediments
      are polluted is described. This framework is intended to be sufficiently
      prescriptive to standardize the decision-making process but without using "cook
      book" assessments. It emphasizes 4 guidance "rules": (1) sediment chemistry data
      are only to be used alone for remediation decisions when the costs of further
      investigation outweigh the costs of remediation and there is agreement among all
      stakeholders to act; (2) remediation decisions are based primarily on biology;
      (3) lines of evidence (LOE), such as laboratory toxicity tests and models that
      contradict the results of properly conducted field surveys, are assumed
      incorrect; and (4) if the impacts of a remedial alternative will cause more
      environmental harm than good, then it should not be implemented. Sediments with
      contaminant concentrations below sediment quality guidelines (SQGs) that predict
      toxicity toless than 5% of sediment-dwelling infauna and that contain no
      quantifiable concentrations of substances capable of biomagnifying are excluded
      from further consideration, as are sediments that do not meet these criteria but
      have contaminant concentrations equal to or below reference concentrations.
      Biomagnification potential is initially addressed by conservative (worst case)
      modeling based on benthos and sediments and, subsequently, by additional food
      chain data and more realistic assumptions. Toxicity (acute and chronic) and
      alterations to resident communities are addressed by, respectively, laboratory
      studies and field observations. The integrative decision point for sediments is a
      weight of evidence (WOE) matrix combining up to 4 main LOE: chemistry, toxicity,
      community alteration, and biomagnification potential. Of 16 possible WOE
      scenarios, 6 result in definite decisions, and 10 require additional assessment.
      Typically, this framework will be applied to surficial sediments. The possibility
      that deeper sediments may be uncovered as a result of natural or other processes
      must also be investigated and may require similar assessment.

PMID- 16639883
TI  - Evaluation of criteria used to assess the quality of aquatic toxicity data.
AB  - Good quality toxicity data underpins robust hazard and risk assessments in
      aquatic systems and the derivation of water quality guidelines for ecosystems.
      Hence, an objective scheme to assess the quality of toxicity data forms an
      important part of this process. The variation of scores from 2 research papers
      using the Australasian ecotoxicity database (AED) quality assessment scheme was
      evaluated by 23 ecotoxicologists. The results showed that the quality class that
      the assessors gave each paper varied by less than 10% when compared with a
      quality score agreed a priori between the authors of this study. It was
      determined that the majority of the variation in each assessment was due to
      ambiguous or poorly written assessment criteria, information that was difficult
      to find, or information in the paper that was overlooked by the assessor. This
      led to refinements of the assessment criteria in the AED, which resulted in a 16%
      improvement (i.e., reduction) in the mean variation of scores for the 2 papers
      when compared with the a priori scores. The improvement in consensus among
      different assessors evaluating the same research papers suggests that the data
      quality assessment scheme proposed in this article provides a more robust scheme
      for assessing the quality of aquatic toxicity data than methods currently
      available.

PMID- 16639884
TI  - Human-toxicological effect and damage factors of carcinogenic and noncarcinogenic
      chemicals for life cycle impact assessment.
AB  - Chemical fate, effect, and damage should be accounted for in the analysis of
      human health impacts by toxic chemicals in life-cycle assessment (LCA). The goal
      of this article is to present a new method to derive human damage and effect
      factors of toxic pollutants, starting from a lognormal dose-response function.
      Human damage factors are expressed as disability-adjusted life years (DALYs).
      Human effect factors contain a disease-specific and a substance-specific
      component. The disease-specific component depends on the probability of disease
      occurrence and the distribution of sensitivities in the human population. The
      substance-specific component, equal to the inverse of the ED50, represents the
      toxic potency of a substance. The new method has been applied to calculate
      combined human damage and effect factors for 1,192 substances. The total range of
      7 to 9 orders of magnitude between the substances is dominated by the range in
      toxic potencies. For the combined factors, the typical uncertainty, represented
      by the square root of the ratio of the 97.5th and 2.5th percentile, is a factor
      of 25 for carcinogenic effects and a factor of 125 for noncarcinogenic effects.
      The interspecies conversion factor, the (non)cancer effect conversion factor, and
      the average noncancer damage factor dominate the overall uncertainty.

PMID- 16639885
TI  - A case study of the Australian Plague Locust Commission and environmental due
      diligence: why mere legislative compliance is no longer sufficient for
      environmentally responsible locust control in Australia.
AB  - The Australian Plague Locust Commission (APLC) manages locust populations across
      2 million square kilometers of eastern Australia using the aerial application of
      chemical and biological control agents to protect agricultural production. This
      occurs via a preventative control strategy involving ultralow-volume spray
      equipment to distribute small droplets of control agent over a target area. The
      economic costs of, and potential gains stemming from, locust control are well
      documented. The application of insecticides, however, to fragile arid and
      semiarid ecosystems is a task that brings with it both real and perceived
      environmental issues. The APLC is proactive in addressing these issues through a
      combination of targeted environmental operational research, an ISO-14001-aligned
      Environmental Management System (EMS), and links with environmental regulatory
      and research institutions. Increasing due diligence components within Australian
      environmental legislation dictate that mere legislative compliance is no longer
      sufficient for industries to ensure that they meet their environmental
      obligations. The development of external research links and the formulation of an
      EMS for locust control have enabled the APLC to identify environmental issues and
      trends, quantify objective environmental targets and strategies, and facilitate
      continuous improvement in its environmental performance, while maintaining
      stakeholder support. This article outlines the environmental issues faced by the
      APLC, the research programs in place to address these issues, and the procedures
      in place to incorporate research findings into the organization's operational
      structure.

PMID- 16639886
TI  - Soil type-specific environmental quality standards for zinc in Dutch soil.
AB  - The heavy metal zinc is an element of natural origin. Adverse effects of
      chemicals on soil ecosystems depend on the soil type. Therefore, soil type
      specific variation in natural background concentration and toxicity data should
      be taken into account in the derivation of environmental quality standards for
      zinc. In this paper, a methodology is presented, taking the specific features of
      natural occurrence and soil type into account by deriving soil type-specific
      background concentrations as well as soil type-specific maximum permissible
      additions (MPAs) for zinc in Dutch soil. The strategy used to perform a soil type
      specific risk assessment for zinc consisted of 6 steps: identification of soil
      types, determination of characteristic background concentrations, selection of
      characteristic organisms, determination of no-observed-effect concentrations
      (NOECs), and derivations of the MPA and the maximum permissible concentration
      (MPC). Differences in background concentrations between different Dutch soil
      types were up to a factor of 7.5, whereas the MPA between the soil types varied
      by up to a factor of 3. This resulted in MPCs for the 3 predominant soil types
      that vary from 44 mg/kg dry weight (dry wt) to 208 mg/kg dry wt. Although large
      differences in MPC were observed, the uncertainties in background concentrations
      hinder setting more accurate environmental quality standards for zinc. Additional
      measurements on remote background concentrations of zinc in Dutch soil are needed
      to reduce the uncertainties in the calculated MPCs. The risk assessment approach
      discussed here is widely applicable to naturally occurring and anthropogenic
      substances.

PMID- 16639887
TI  - Improving risk assessments for manufactured gas plant soils by measuring PAH
      availability.
AB  - Remediation of soils at oil-gas manufactured gas plant (MGP) sites is driven
      primarily by the human health risks posed by the carcinogenic polycyclic aromatic
      hydrocarbons (PAHs), particularly benzo[a]pyrene (BaP), that are associated with
      lampblack residues. Although PAHs on lampblack are tightly sorbed, risk
      assessments do not account for this reduced availability. A multi-investigator
      study of 7 oil-gas MGP site soil samples demonstrated that the dermal and
      ingestion absorption factors are far lower than current default assumptions used
      in risk assessments. Using these sample-specific absorption factors in standard
      risk assessment equations increased risk-based cleanup levels by a factor of 72
      on average (with a range from 23 to 142 times the default level). The rapidly
      released fraction of the BaP in each sample, as measured by supercritical fluid
      extraction, was closely correlated (r2 = 0.96) to these calculated cleanup
      levels. The weight of evidence developed during this research indicates that the
      risks posed by PAHs on lampblack are far less than assumed when using default
      absorption factors and that a tiered evaluation protocol employing chemical
      analyses, chemical release data, and in vitro bioassays can be used to establish
      more realistic site-specific criteria.

PMID- 16639888
TI  - Potential impact of Dare County landfills on Alligator River National Wildlife
      Refuge.
AB  - Runoff of leachate from East Lake and Dare County Construction and Demolition
      Debris landfills has the potential to impact wildlife resources at Alligator
      River National Wildlife Refuge, Dare and Hyde Counties, North Carolina. Sediment
      quality of samples collected in August 2000 at 14 locations down-gradient from
      the landfills was assessed by measuring metal and organic contaminants in the
      sediments, chronic toxicity of solid-phase sediment (28-d static-renewal
      exposures; survival and growth as test endpoints) and acute toxicity of sediment
      porewater (96-h static exposures) to Hyalella azteca (Crustacea: Amphipoda). In
      addition, contaminant bioaccumulation from 4 sediments was determined using 28-d
      exposures of Lumbriculus variegatus (freshwater oligochaete). Although survival
      was not impaired, length of H. azteca was significantly reduced in sediments from
      5 locations. Pore water from 4 locations was acutely toxic to H. azteca. Metals
      and a few polycyclic aromatic hydrocarbons (PAHs) were bioaccumulated by L.
      variegatus from the sediments. Several metals and PAHs exceeded sediment quality
      guidelines, and metals in porewater from several sites exceeded water quality
      criteria for the protection of aquatic wildlife. Runoff of leachate from the
      landfills has reduced sediment quality and has the potential to adversely affect
      wildlife resources at Alligator River National Wildlife Refuge.

PMID- 16639889
TI  - The impact of mining activities on Mongolia's protected areas: a status report
      with policy recommendations.
AB  - Mongolia's protected areas cover 20.5 million ha or 13.1% of its national
      territory. Existing and proposed protected areas, however, are threatened by
      mining. Mining impacts on Mongolia's protected areas are diverse and include
      licensed and unlicensed mineral activities in protected areas, buffer zone
      disturbance, and prevention of the establishment of proposed protected areas.
      Review of United States, Canadian, and Australian policies revealed 9 basic
      approaches to resolving conflicts between protected areas and mining. Four
      approaches suitable for Mongolia are granting land trades and special
      dispensations in exchange for mineral licenses in protected areas; granting
      protected status to all lapsed mineral licenses in protected areas; voluntary
      forfeiting of mineral licenses in protected areas in exchange for positive
      corporate publicity; and prohibiting all new mineral activities in existing and
      proposed protected areas. Mining is Mongolia's most important industry, however,
      and the long-term benefits of preserving Mongolia's natural heritage must be
      considered and weighed against the economic benefits and costs of mining
      activities.

PMID- 16639890
TI  - Two simple algorithms for refining mammalian receptor selection in ecological
      risk assessments.
AB  - Although guidelines exist for selecting appropriate ecological receptors for risk
      assessments at contaminated sites, it can be demonstrated that many of the
      mammals commonly evaluated are spatially irrelevant. Terrestrial risk assessments
      could be simplified and made more efficient, though, if mammals that are
      initially considered were screened for their spatial relevance. This article
      presents 2 simple algorithms that each demonstrate that most mammalian receptors
      are not spatially relevant for the overwhelming majority of hazardous waste and
      other contaminated sites. The algorithms use readily available and curiously
      overlooked spatial distribution (e.g., animal density) information and suggest
      that contaminated sites need to be 80 to 100 acres in size to justify the
      inclusion of most mammalian receptors. Given that hazardous waste sites are
      generally much smaller than this, many ecological risk assessments (ERA) could
      reasonably dispense with incorporating mammals entirely. An awareness on the part
      of decision makers and risk managers of the nonsuitability of many mammalian
      receptors evaluated in terrestrial ERAs could significantly impact the perceived
      need to monitor or remediate sites. This article also examines the anticipated
      challenges of regulators and other decision makers when entertaining the notion
      of a spatial relevance screen for mammals.

PMID- 16639891
TI  - Application of multicriteria decision analysis in environmental decision making.
AB  - Decision making in environmental projects can be complex and seemingly
      intractable, principally because of the inherent trade-offs between
      sociopolitical, environmental, ecological, and economic factors. The selection of
      appropriate remedial and abatement strategies for contaminated sites, land use
      planning, and regulatory processes often involves multiple additional criteria
      such as the distribution of costs and benefits, environmental impacts for
      different populations, safety, ecological risk, or human values. Some of these
      criteria cannot be easily condensed into a monetary value, partly because
      environmental concerns often involve ethical and moral principles that may not be
      related to any economic use or value. Furthermore, even if it were possible to
      aggregate multiple criteria rankings into a common unit, this approach would not
      always be desirable because the ability to track conflicting stakeholder
      preferences may be lost in the process. Consequently, selecting from among many
      different alternatives often involves making trade-offs that fail to satisfy 1 or
      more stakeholder groups. Nevertheless, considerable research in the area of
      multicriteria decision analysis (MCDA) has made available practical methods for
      applying scientific decision theoretical approaches to complex multicriteria
      problems. This paper presents a review of the available literature and provides
      recommendations for applying MCDA techniques in environmental projects. A
      generalized framework for decision analysis is proposed to highlight the
      fundamental ingredients for more structured and tractable environmental decision
      making.

PMID- 16639892
TI  - How closely do acute lethal concentration estimates predict effects of toxicants
      on populations?
AB  - Acute lethal dose/concentration estimates are the most widely used measure of
      toxicity and these data often are used in ecological risk assessment. However,
      the value of the lethal concentration (LC50) as a toxicological endpoint for use
      in ecological risk assessment recently has been criticized. A question that has
      been asked frequently is how accurate is the LC50 for prediction of longer-term
      effects of toxicants on populations of organisms? To answer this question,
      Daphnia pulex populations were exposed to nominal concentrations equal to the 48
      h acute LC50 of 6 insecticides, Actara, Aphistar diazinon, pymetrozine, Neemix,
      and Spinosad; and 8 agricultural adjuvants, Bond, Kinetic, Plyac, R-11, Silwet,
      Sylgard 309, Water Maxx, and X-77; for 10 d. None of the D. pulex populations
      exposed to the acute LC50 of these insecticides were 50% lower than the control
      populations at the end of the study; exposure to diazinon resulted in populations
      that were higher than expected (91% of the control). Exposure to Actara and
      Aphistar resulted in populations that were < 1 and 29% of the control,
      respectively. Exposure to Fulfill, Neemix, and Spinosad resulted in extinction.
      Extinction occurred after exposure to all of the adjuvants, except Silwet L-77
      where the population was 31% of the control. These results corroborate other
      studies that indicate that the LC50 is not a good predictor of effects on
      population growth. Although lethal concentration estimates have their place in
      toxicology, namely to compare intrinsic toxicity of chemicals among species or
      susceptibility of a species to different chemicals over short time periods,
      population growth and growth-rate studies are necessary to predict toxicant
      effects on populations.

PMID- 16639893
TI  - Toxicity assessment of environmentally relevant pollutant mixtures using a
      heuristic model.
AB  - In this study, 9 chemicals were chosen from a recent report on surface water
      concentrations of a variety of xenobiotics to test the hypothesis that the
      toxicity of chemical mixtures could be estimated using a model based on the
      toxicity of the individual chemicals. Concentration-response curves for the
      endpoints of lifespan, growth rate, and fecundity were generated for each
      chemical experimentally using the crustacean, Daphnia magna. From this data, a
      mathematical model for the combined toxicity of these chemicals was generated
      that merged the concepts of concentration addition and independent joint action.
      Toxicity of a mixture was modeled at various levels at which the ratio of the
      chemicals within the mixture was maintained at that reported for median detected
      environmental levels. Toxicity of the mixture was then determined experimentally
      and compared to model predictions. The model accurately predicted the most
      sensitive endpoint, as well as the lowest toxic effect level of the mixture.
      Results demonstrated that, for this mixture of chemicals, toxicity was not
      influenced significantly by interactions among the chemicals and a single
      constituent dominated toxicity. According to model predictions and experimental
      results, the median detected environmental concentrations of chemicals
      constituting this mixture provided no margin of safety.

PMID- 16639894
TI  - Ecological effects of pesticide use in The Netherlands: modeled and observed
      effects in the field ditch.
AB  - This study addresses the potential risks to the aquatic ecosystem posed by
      pesticides currently used in The Netherlands. The study used a novel method to
      predict aquatic exposure to pesticides based on a geographic information system
      (GIS) map of agricultural land use, comprising 51 crops used in open-canopy
      areas. Through the application of species-sensitivity distributions for aquatic
      organisms, in combination with rules for mixture-toxicity calculation, the
      modeled exposure results were transformed to risk estimates for aquatic species.
      The majority of the predicted risks were caused by pesticides applied to potato
      cropland, and approximately 95% of the predicted risk was caused by only 7 of the
      261 pesticides currently used in The Netherlands. For risk verification, local
      toxic-risk estimates were compared with observed species composition in field
      ditches. The field verification study was not able to draw firm conclusions
      regarding the predicted impact of pesticide use on overall biodiversity. A
      toxicity-related shift from sensitive to more tolerant or opportunistic species
      could be observed for a few species.

PMID- 16639895
TI  - Indoor air quality investigation and health risk assessment at correctional
      institutions.
AB  - A comprehensive indoor air-quality (IAQ) investigation was conducted at a state
      correctional facility in New Jersey, USA with a lengthy history of IAQ problems.
      The IAQ investigation comprised preliminary indoor air screening using direct
      readout instrumentation, indoor air/surface wipe sampling and laboratory
      analysis, as well as a heating, ventilation, and air-conditioning system
      evaluation, and a building envelope survey. In addition to air sampling, a human
      health risk assessment was performed to evaluate the potential for exposure to
      site-related air contaminants with respect to the inmate and worker populations.
      The risk assessment results for the prison facility indicated the potential for
      significant health risks for the inmate population, possibly reflecting the
      effects of their confinement and extended exposure to indoor air contaminants, as
      compared to the prison guard and worker population. Based on the results of the
      risk assessment, several mitigation measures are recommended to minimize prison
      population health risks and improve indoor air quality at prison facilities.

PMID- 16639896
TI  - A methodology for deriving tissue residue benchmarks for aquatic biota: a case
      study for fish exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and equivalents.
AB  - Tissue residue-based toxicity benchmarks (TRBs) have typically been developed
      using the results of individual studies selected from the literature. In the
      past, TRBs have been developed using a point estimate (e.g., LC50 value) reported
      in a study on a single species deemed to be most closely related to the receptor
      of interest. Despite attempts to maximize the protectiveness and relevance of
      TRBs, their relationship to specific receptors remains uncertain, and their
      general applicability for use in broader ecological risk assessment contexts is
      limited. This article proposes a novel framework that establishes benchmarks as
      distributions rather than single-point estimates. Benchmark distributions allow
      the user to select a tissue concentration that is associated with the protection
      of a specific percentage of organisms, rather than linked to a specific receptor.
      A methodology is proposed for searching, reviewing, and analyzing linked, tissue
      residue effect data to derive benchmark distributions. The approach is
      demonstrated for contaminants having a dioxin-like mechanism of toxic action and
      is based on residue effects data for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8
      TCDD) and equivalents in early life stage fish. The calculated tissue residue
      benchmarks for 2,3,7,8-TCDD toxic equivalency (TEQ) derived from the resulting
      distribution could range from 0.057- to 0.699-ng TCDD/g lipid depending on the
      level of protection needed; the lower estimate is protective of 99% of fish
      species whereas the higher end is protective of 90% of fish species.

PMID- 16639897
TI  - An evaluation of United Kingdom environmental bovine spongiform encephalopathy
      risk assessment.
AB  - As a member of the group of diseases known as transmissible spongiform
      encephalopathies (TSEs), bovine spongiform encephalopathy (BSE) has been causally
      associated with a new variant of Creutzfeldt-Jakob disease (vCJD) in humans.
      Given the many uncertainties on the transmission and persistence of TSE pathogens
      in the environment, quantitative assessment of risks to humans and animals
      continues to remain a public health issue. This paper reviews quantitative BSE
      risk assessments undertaken in the United Kingdom since 1997 to address the
      potential for human exposure and theoretical health risks through environmental
      pathways. The review focuses on how model assumptions and methodology may
      influence the results.

PMID- 16639898
TI  - The European Union risk assessment on zinc and zinc compounds: the process and
      the facts.
AB  - A risk assessment on zinc and zinc compouns was carried out withn the framework
      of Council Regulation 793/93/EEC on Existing Chemicals. This risk assessment
      basically followed the European Union (EU) technical guidance documents (TGDs).
      These TGDs are built on the current knowledge on quantitative risk assessments,
      mainly for organic chemicals. This article describes the tailor-made approach for
      the zinc risk assessment. This work lasted almost a decade and involved the
      contributions of all EU member states and industry, who discussed the risk
      assessment during technical meetings. The risk assessment is initially based on
      scientific findings but is interrelated with pragmatic considerations. It follows
      a comprehensive approach, covering both environmental and human health. In the
      environmental part, new methodologies were developed to deal with the natural
      background of zinc, essentiality, speciation, and the use of species sensitivity
      distributions. The major results and the process of drawing conclusions of the
      risk assessment are outlined: potential environmental risks of zinc and zinc
      compounds may occur at local and regional scales in surfacewater, sediment, and
      soil. No potential health risks were identified for consumers and man indirectly
      exposed via the environment. For workers, potential health risks were identified
      only for zinc oxide and zinc chloride.

PMID- 16639899
TI  - Survey of methodologies for developing media screening values for ecological risk
      assessment.
AB  - This review evaluates the methodologies of 13 screening value (SV) compilations
      that have been commonly used in ecological risk assessment (ERA), including
      compilations from state and U.S. federal agencies, the Oak Ridge National
      Laboratory (ORNL), Canada, The Netherlands, and Australia. The majority of
      surfacewater SVs were primarily derived for the protection of aquatic organisms
      using 2 approaches: (1) a statistical assessment of toxicity values by species
      groupings, such as "ambient water quality criteria," or (2) extrapolation of a
      lowest observed adverse effect level determined from limited toxicity data using
      an uncertainty factor. Sediment SVs were primarily derived for the protection of
      benthic invertebrates using 2 approaches: (1) statistical interpretations of
      databases on the incidence of biological effects and chemical concentrations in
      sediment, or (2) values derived from equilibrium partitioning based on a
      surfacewater SV. Soil SVs were derived using a diversity of approaches and were
      usually based on the lowest value determined from soil toxicity to terrestrial
      plants or invertebrates and, less frequently, from modeled, incidental soil
      ingestion or chemical accumulation in terrestrial organisms. The various SV
      compilations and methodologies had varying levels of conservatism and were not
      consistent in the pathways and receptors considered in the SV derivation. Many
      SVs were derived from other compilations and were based on outdated values, or
      they relied on only older toxicity data. Risk assessors involved in ERA should
      carefully evaluate the technical basis of SVs and consider the uncertainty in any
      value used to determine the presence or absence of risk and the need for further
      assessment.

PMID- 16639900
TI  - Estimations of copper roof runoff rates in the United States.
AB  - Copper (Cu) concentrations in waterways of the United States are of widespread
      concern. Presently, 692 waterway segments around the United States are listed by
      the U.S. Environmental Protection Agency (USEPA) as having unacceptably high
      copper concentrations. As part of their water quality management strategy, the
      USEPA is mandated to understand and manage sources and impacts of nonpoint
      releases of chemicals of concern. One potential nonpoint source of Cu is the
      runoff of precipitation falling onto Cu used in external architecture (e.g.,
      roofing). However, few studies of Cu roof runoff have been published. This
      article is intended to provide estimations of Cu runoff rates and concentrations
      across the United States. Copper runoff rates and concentrations are predicted at
      179 locations with a recently developed model. The average and range (in
      parentheses) of annual Cu loading rates, based on roof area; Cu export rates,
      based on amount of precipitation; and Cu concentrations for the United States are
      2.12 (1.05-4.85) g Cu/m2/y; 2.72 (0.69-16.48) mg Cu/m2/ mm; and 2.72 (0.69-16.48)
      mg Cu/L as total Cu, respectively. Statistics are presented that describe site
      specific data distributions for use in probabilistic exposure and risk
      assessments. The effects of air quality as well as the potential fate and risks
      of Cu from roof runoff are discussed.

PMID- 16639901
TI  - Polybrominated diphenylether levels among United States residents: daily intake
      and risk of harm to the developing brain and reproductive organs.
AB  - Data on Polybrominated diphenylether (PBDE) concentrations in individual U.S.
      women were compiled. PBDE levels in adipose tissue, serum, and breast milk from
      individual U.S. women were found to follow similar lognormal distributions, which
      exhibited a high degree of variability. The distribution of lipid-normalized PBDE
      concentrations for all media combined had a median of 47.9 ng/g and a 95th
      percentile estimate of 302 ng/g. Estimates of congener-specific kinetic
      parameters were used to calculate the total daily intake of the PBDEs (sum of 5
      PBDE prominent congeners, PBDE-47, -99, -100, -153, and -154) that would be
      required to achieve the measured body burdens. PBDE intake estimates from all
      routes of exposure were 8.5 ng/kg/d (median) and 54 ng/kg/d (95th percentile).
      The potential health risks posed by the PBDEs were examined by comparing 95th
      percentile tissue concentrations in humans (C(human)) to modeled and measured
      tissue concentrations in rodents that caused no developmental neurotoxicity and
      reproductive effects (C(rodent)). The ratio of rodent-to-human PBDE
      concentrations (C(rodent):C(human)) was <1 for alterations of male and female
      reproductive organs in rats, <10 for neurodevelopmental effects in mice, and <100
      for neurodevelopmental effects in rats. If humans are as sensitive as animals to
      PBDE-induced developmental toxicity, the current margin of safety appears low for
      a fraction of the population.

PMID- 16639902
TI  - Analysis of environmental effects of the use of stabilized dredged material from
      New York/New Jersey Harbor, USA, for construction of roadway embankments.
AB  - Since the 1997 local ban on ocean dumping of dredged sediments, the state of New
      Jersey has pursued a policy of environmentally sound solutions to the
      controversial problem of dredged material management, including beneficial use of
      dredged material stabilized with pozzolanic additives (SDM). A pilot study was
      initiated in 1998 to evaluate the use of SDM in the construction of highway
      embankments. Using 80,000 cubic yards of silty dredged material, 2 embankments
      were constructed from SDM on a commercial development area adjacent to the New
      York/New Jersey Harbor. This article presents the evaluation of the environmental
      effects of the SDM, including fugitive air emissions, leachate, and stormwater
      quality. Engineering properties, handling and management techniques of the SDM,
      constructability, and performance were also evaluated, the results of which are
      published elsewhere. The findings demonstrate that although there are measurable
      releases of contaminants to the environment from the SDM, these releases are not
      significant long-term threats to human health or the environment. Policies
      currently in place to regulate the management of SDM that include limiting
      placement options to previously contaminated sites with institutional and
      engineering controls will further reduce the potential for environmental impact
      and, in fact, have the potential to produce significant environmental benefit.

PMID- 16639903
TI  - Impacts of gold mining and land use alterations on the water quality of central
      Mongolian rivers.
AB  - Conservation of water quality is inherently tied to watershed management. Efforts
      to proect Lake Baikal have increasingly focused on the Selenge River, a major
      tributary, with more than half its watershed area in Mongolia. Placer gold mining
      in Mongolia has the potential to load total suspended sediment (TSS), and total
      phosphorus (TP) into Lake Baikal and destroy spawning areas for the endangered
      Taimen salmon (Hucho taimen taimen). This work describes water quality
      assessments performed from 2001 to 2003 on Mongolian tributaries to the Selenge
      River. Of 7 rivers sampled, rivers with proximal mining had the worst water
      quality. Elevated loading of TSS and TP was observed below mining regions on the
      Tuul River. Flooding could breach thin strips of land separating dredge pits from
      river channels, resulting in massive sediment loading. Extensive disturbance of
      the river terrace was apparent for many square kilometers. In the mountainous
      headwaters of the Yeroo River, tributary drainages undergoing mining had TP
      concentrations 8 to 15 times higher than the main stem. TSS was 7 to 12 times
      higher, and turbidity was 8 times higher. Alternative mining technologies exist
      that could minimize impact and improve the possibility for reclamation.

PMID- 16639904
TI  - Incremental ecological exposure risks from contaminated sediments in an urban
      estuarine river.
AB  - Estuaries in urban regions present unique environmental management challenges.
      Ecosystems in urban estuaries are typically impacted by habitat loss and
      degradation, watershed modification, and nonpoint and point sources of many
      chemicals. Restoring such systems requires an understanding of the relative
      contribution of various stressors to overall ecological conditions and an
      understanding of shifting patterns of stress over time. In this article, we
      present the results of a multiparameter environmental assessment of a
      quintessential urbanized waterway: the lower Passaic River in the vicinity of
      Newark, New Jersey, USA. To provide the foundation for effective management
      decision making, we quantified baseline conditions (habitat losses and
      degradation), chemical concentrations in sediment and biota relative to published
      toxic effect levels, direct toxicity of sediments to benthic organisms, and food
      web mediated risks to fish-eating birds. Habitat losses have been severe (greater
      than 85% of wetlands, nearly 100% of the total length of tidal and nontidal
      tributaries, and 100% of natural shoreline habitat have been lost), resulting in
      substantial habitat constraints on biota. Despite this, biological communities
      are present in the lower Passaic. In general, concentrations of toxic chemicals
      in surface sediments have fallen with time, and natural recovery processes are
      proceeding. Chemical concentrations remain high enough to impair survival of
      amphipods, but not amphipod growth or polychaete growth or survival as measured
      in laboratory bioassays using field-collected sediment. Fish and blue crab body
      burdens of some metals, PCBs, and the pesticide, DDT, are at concentrations
      sufficiently high to exceed toxicity thresholds. The resident fish-eating bird-
      the belted kingfisher--is at exposure risk from some metals, PCBs, and
      polychlorinated dibenzo-p-dioxins and dibenzo furans (PCDD/Fs). Migratory waders-
      the herons and egrets--are not at risk from chemical exposure. These complex
      findings suggest that restoring the lower Passaic River to ecological health is a
      correspondingly complex task. Habitat constraints must be eased for biotic
      components of the ecosystem, and chemical effects must be reduced for those
      organisms that are present. Only a coordinated, multidisciplinary restoration
      program will succeed in this challenging environment.

PMID- 16639905
TI  - Actinides in deer tissues at the rocky flats environmental technology site.
AB  - Limited hunting of deer at the future Rocky Flats National Wildlife Refuge has
      been proposed in U.S. Fish and Wildlife planning documents as a compatible
      wildlife-dependent public use. Historically, Rocky Flats site activities resulted
      in the contamination of surface environmental media with actinides, including
      isotopes of americium, plutonium, and uranium. In this study, measurements of
      actinides [Americium-241 (241Am); Plutonium-238 (238Pu); Plutonium-239,240
      (239,240Pu); uranium-233,244 (233,234U); uranium-235,236 (235,236U); and uranium
      238 (238U)] were completed on select liver, muscle, lung, bone, and kidney tissue
      samples harvested from resident Rocky Flats deer (N = 26) and control deer (N =
      1). In total, only 17 of the more than 450 individual isotopic analyses conducted
      on Rocky Flats deer tissue samples measured actinide concentrations above method
      detection limits. Of these 17 detects, only 2 analyses, with analytical
      uncertainty values added, exceeded threshold values calculated around a 1 x 10(
      6) risk level (isotopic americium, 0.01 pCi/g; isotopic plutonium, 0.02 pCi/g;
      isotopic uranium, 0.2 pCi/g). Subsequent, conservative risk calculations suggest
      minimal human risk associated with ingestion of these edible deer tissues. The
      maximum calculated risk level in this study (4.73 x 10(-6)) is at the low end of
      the U.S. Environmental Protection Agency's acceptable risk range.

PMID- 16639906
TI  - Individuals versus organisms versus populations in the definition of ecological
      assessment endpoints.
AB  - Discussions and applications of the policies and practices of the U.S.
      Environmental Protection Agency (USEPA) in ecological risk assessment will
      benefit from continued clarification of the concepts of assessment endpoints and
      of levels of biological organization. First, assessment endpoint entities and
      attributes can be defined at different levels of organization. Hence, an organism
      level attribute, such as growth or survival, can be applied collectively to a
      population-level entity such as the brook trout in a stream. Second, assessment
      endpoints for ecological risk assessment are often mistakenly described as
      "individual level," which leads to the idea that such assessments are intended to
      protect individuals. Finally, populations play a more important role in risk
      assessments than is generally recognized. Organism-level attributes are used
      primarily for population-level assessments. In addition, the USEPA and other
      agencies already are basing management decisions on population or community
      entities and attributes such as production of fisheries, abundance of migratory
      bird populations, and aquatic community composition.

PMID- 16639907
TI  - International Tinnitus Forum, Twenty-Third Annual Meeting: Translational Research
      in Tinnitus Therapy.

PMID- 16639908
TI  - World, senses, human spirit: extrapolating the direction from the past through
      the present and into the future.

PMID- 16639909
TI  - Ultra-high-frequency ultrasonic external acoustic stimulation for tinnitus
      relief: a method for patient selection.
AB  - We proposed a method for patient selection and application of criteria for
      predicting success with bone-conduction external acoustic stimulation using high
      audio-frequency sound in the ranges of 10-20 kHz and 20-26 kHz for individuals
      with subjective idiopathic tinnitus (SIT) of the severe disabling type. Ultra
      high-frequency (UHF) stimulation for tinnitus relief has been found to be most
      effective when residual neuronal function exists in the acoustic ranges of 10-14
      kHz, with thresholds no greater than 40-50 dB sound pressure level (SPL).
      Ultrasonic (US) acoustic stimulation is recommended for patients with audiometric
      thresholds greater than 50-60 dB SPL for frequencies of 10-14 kHz. Fifty-two
      consecutive patients seen for the primary complaint of SIT of the severe
      disabling type received a trial of either UHF or US bone-conduction acoustic
      stimulation. Tinnitus relief was reported in 22 of the 52 patients. The
      application of criteria for patient selection predicted tinnitus relief in 20 of
      the 22.

PMID- 16639910
TI  - Prognosis for sudden sensorineural hearing loss: a retrospective study using
      logistical regression analysis.
AB  - Sudden sensorineural hearing loss (SSNHL) remains a controversial problem with
      respect to etiology and the factors that might predict prognosis. We used
      logistical regression analysis to determine which factors are most strongly
      related to outcome for patients with SSNHL. In so doing, we employed a
      retrospective chart-review study. The study group consisted of 296 patients (296
      ears). The outcome of SSNHL was cured (full recovery) in 64, recovered (partial
      recovery) in 175, and no change in 57. We performed separate analyses on those in
      the no-change and partial-recovery groups and on those in the no-change and full
      recovery groups. The following factors were studied as explanatory variables:
      age; number of days until presentation; vestibular symptom; initial mean hearing
      level at 0.25 kHz, 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz; and treatments (steroids,
      satellite ganglion block). In the first analysis, for patients in the no-change
      and recovered groups, the factors most strongly related to outcome were the
      number of days until presentation and age. The second analysis, for the nochange
      and cured groups, revealed that the number of days until presentation, vestibular
      symptom, age, and initial mean hearing level were most strongly related to
      outcome. Our results will increase the ability to predict the outcome for SSNHL.

PMID- 16639911
TI  - Serotonergic innervation of the inner ear: is it involved in the general
      physiological control of the auditory receptor?
AB  - The auditory pathway of mammals is composed of two complementary ascending
      afferent and descending efferent independent systems. The brainstem nuclei and
      cochlear projections for these systems are now well-known. In addition, a highly
      conspicuous distribution for serotonergic fibers was recently reported. This
      study focused on these serotonergic fibers and their neurons of origin. We
      identified several different types of serotonergic brainstem neurons surrounding
      the superior olivary complex and around the periolivary nuclei. Even though the 5
      hydroxytryptamine (5-HT) efferent cochlear innervation originates in the
      periolivary area of the superior olivary complex system projecting to the
      cochlea, it is not involved in the transduction of pure tones during auditory
      processing. However, recent findings, after cochlear blockade of serotonin
      transporters, strongly suggested that this neuroactive substance has an important
      turnover within the auditory receptor. The presence of a conspicuous peripheral
      nerve distribution together with a particular brainstem origin could define a
      complex role for this innervation. Therefore, 5-HT fibers projecting to the
      cochlea might be involved, as in other parts of the auditory pathway, in
      alertness, attention, control of sleep or wakefulness cycles, and state of
      urgency prior to the transduction processing at the auditory receptor. A lack, or
      reduction, of the function of these fibers could result in pathological
      alterations.

PMID- 16639912
TI  - Subdividing tinnitus into bruits and endogenous, exogenous, and other forms.
AB  - Tinnitus is an important complaint or disease or a combination, especially within
      our aging population. Neurootologists clinically deal with many different
      disorders of the human cranial senses, of which tinnitus is a very frequent type.
      With respect to neurootological clinical work, we delineate at least three groups
      of tinnitus. In bruits, patients complain of noise within the head (e.g.,
      bubbling, hissing, pulsating); the bruit can be recorded as a physically existing
      sound in the human skull and is heard by patients. Endogenous tinnitus can be
      treated by external masking to suppress noise within the ears, whereas in
      exogenous tinnitus, patients seek to avoid any outside noise or sounds; they
      report that tinnitus decreases as soon as they go, for instance, into the cellar
      of a house or other soundproof place.

PMID- 16639913
TI  - Ventriculoperitoneal shunt as treatment for perilymphatic fistula: a report of
      six cases.
AB  - We report six cases of perilymphatic fistula in patients who received
      ventriculoperitoneal shunts as part of their final mode of therapy. The last of
      our 6 patients actually received a ventriculoperitoneal shunt as her initial mode
      of therapy. All but one had benign intracranial hypertension. All six felt better
      (less disequilibrium, tinnitus, and pressure and occasional hearing improvement)
      after LP with removal of 15-20 ml of cerebrospinal fluid.

PMID- 16639914
TI  - P-100 in the treatment of Meniere's disease: a clinical study.
AB  - Patients suffering from Meniere's disease are particularly sensitive to negative
      pressure in the middle ear. For example, attacks of vertigo can be triggered by a
      descent in an aircraft when ventilation of the middle ear can become critical.
      Positive-pressure pulse treatment has been shown to have a beneficial effect on
      the symptomatology and is now a true alternative in the treatment of Meniere's
      disease. In this study, we compared two devices that produced positive-pressure
      pulses delivered to the inner ear via the external ear canal and after the
      insertion of a middle-ear ventilation tube. Both devices (Meniett and P-100) were
      equally successful and confirmed that positive-pressure pulse treatment is a true
      alternative to current treatment modalities. However, the P-100 is the preferred
      device, particularly for its convenience of use and its cost, which is
      considerably lower.

PMID- 16639915
TI  - Personal experiences with vestibular evoked myogenic potentials as a modern
      method of diagnosing vestibular organ lesion and monitoring treatment.
AB  - Vestibular evoked myogenic potentials (VEMPs) appear to represent a new and
      promising technique for the assessment of vestibulospinal reflex function. The
      primary aims of the study described in this article were (1) to record VEMPs in
      normal volunteers using available equipment and to establish a range of norms of
      VEMP parameter values (latency, amplitude); (2) to confirm the saccular origin of
      VEMPs; (3) to assess the diagnostic significance of VEMPs; and (4) to evaluate
      the usefulness of VEMPs in monitoring therapeutic results. The study population
      consisted of 252 patients representing various diagnoses of hearing loss and
      vestibular organ lesion. Twenty-three patients were treated with an antihomotoxic
      remedy, and some received placebo. The results of this study demonstrated that
      VEMPs are helpful in evaluating the physiological and pathological equilibrium
      system and in monitoring reflex reactions after treatment.

PMID- 16639916
TI  - Standardized computed tomographic imaging and dimensions of the round-window
      niche.
AB  - Both the increasing usage of intratympanic medication to the inner ear through
      the round window and the popularity of cochlear implantation have raised interest
      in the anatomy of the round-window niche (RWN). The objectives of this study were
      to measure the RWN and to standardize a computed tomographic projection for
      measuring it. We included patients of all ages who underwent computed tomography
      for various reasons. We measured computed tomographic images acquired from 214
      patients aged 4-85 years and included 414 ears and excluded 14 inflamed "wet"
      ears. We measured depth, width, and shape of the RWN and skull width. The RWN
      dimensions did not change with age, whereas the skull width increased with age in
      both genders throughout the patients' entire life. Folds and soft tissue could
      not be demonstrated in computed tomographic imaging. In conclusion, a special
      oblique projection that clearly demonstrates the RWN was reconstructed, and this
      reconstruction allows for standardized measuring.

PMID- 16639917
TI  - Auditive stimulation therapy as an intervention in subacute and chronic tinnitus:
      a prospective observational study.
AB  - Tinnitus is a noise, a ringing, or a roaring sound in the affected ear and is
      becoming an increasingly serious problem for health care systems. Integrative
      treatment concepts are currently regarded as promising therapeutic approaches for
      managing tinnitus. The aim of this study was to present the results of auditive
      stimulation therapy, a program of music therapy developed specifically for
      tinnitus treatment. We collected data on outpatient treatment results from 155
      tinnitus patients and evaluated them in a prospective observational study with
      three defined times of measurement (start, end, and 6 months after the end of
      treatment). Apart from anamnestic data and subjective evaluation of treatment,
      the major outcome parameter was the score of the tinnitus questionnaire. To
      evaluate effectiveness of the therapy, we calculated effect sizes (according to
      Cohen). Fifty-one percent of the patients were male, and the mean patient age was
      49 years. Of the 155 patients, 137 (88%) were capable of gainful employment,
      which means that they fell in the age range between 18 and 65 years. The duration
      of tinnitus was more than 6 months for 80% of patients, and 43% had been
      suffering from tinnitus for more than 3 years. In general, all subscales of the
      tinnitus questionnaire showed highly significant changes (t-test, p < .01)
      between the measurement points "start of therapy" and "end of therapy," whereas
      no significant difference was found between the measurement points "end of
      therapy" and "follow-up". At follow-up, the values of the subscales were
      stabilized at a level recorded at the end of the therapy; we did not observe a
      reduction to the level prior to treatment. The values for the effect sizes mostly
      ranged between medium (> 0.5) and high (> 0.8). Closer investigations indicated
      that a combination of music therapy and psychological training rendered the best
      effect sizes. This study demonstrated that music therapy is an effective
      integrated treatment approach and offers a way to make progress in tinnitus
      treatment.

PMID- 16639918
TI  - Glucose and insulin profiles and their correlations in Meniere's disease.
AB  - Changes in carbohydrate metabolism, admittedly one of the most prevalent
      etiologies of Meiere's syndrome, can be diagnosed early by 5-hour glucose and
      insulin curves with a 100-g glucose load, a test more sensitive than those
      traditionally used in investigating impaired glucose tolerance or diabetes
      mellitus. This study investigated carbohydrate metabolism characteristics in 64
      patients with typical Meniere's disease. We demonstrated that 72% of them had
      some variable degree of hyperinsulinemia as shown by their plasma insulin curves,
      whereas alterations on the glucose curve (reactive hypoglycemia or hyperglycemia)
      were found for only 21%. More advanced hyperinsulinemic conditions (i.e., glucose
      intolerance or diabetes mellitus) were usually associated with changes in lipid
      profiles and with a central pattern of fat distribution and systemic
      hypertension. We found a very strong correlation between insulin concentrations
      measured by chemoluminescence and by radioimmunoassay; the latter, however,
      showed values 1.3 times higher than those measured by chemoluminescence. These
      findings confirm the need to include 5-hour glucose and insulin curves in the
      diagnostic routine when investigating Meniere's disease. In that way, an early
      diagnosis of hyperinsulinemia, the metabolic change most often involved in the
      pathogenesis of cochleovestibular disorders, can be made.

PMID- 16639919
TI  - Nystagmus reactions among patients with asymptomatic cerebrovascular diseases:
      results and analysis of investigation of 228 persons.
AB  - The aim of this investigation was to view characteristics of vestibular nystagmus
      (spontaneous, latent, and positional) through Frenzel's spectacles in patients
      with asymptomatic cerebrovascular disease (ACVD), with the intent of providing an
      early diagnosis and appropriate prophylaxis. We examined a total of 228 men (mean
      age, 48.04 +/- 7.8 years), a mean group of 150 men with proven asymptomatic
      cerebrovascular disease, and 78 clinically healthy men. Vestibular nystagmus was
      investigated through Frenzel's spectacles. The following characteristics
      (qualitative and quantitative) were studied: degree and direction form,
      association, continuity, frequency, and amplitude. It was found that in patients
      with proven ACVD, latent nystagmus is prevalent. The symptom of positional
      nystagmus is much more frequent than that of spontaneous nystagmus and is often
      the first objective symptom of initial disturbances of the cerebral blood flow in
      the region of the vertebrobasilar system. The vestibular system is mainly
      labyrinthine in origin, becoming later of central origin.

PMID- 16639920
TI  - The use of recombinant tissue-type plasminogen activator for the treatment of
      sudden and chronic hearing loss.
AB  - We treated 80 patients with sudden hearing loss and 70 patients with chronic
      decreasing cochlear function to date with intravenous infusion of a glycoprotein
      analogous to recombinant tissue-type plasminogen activator (rt-PA): 3 mg
      dissolved in 250 mg of physiological saline given every 12 hours intravenously.
      Specifically excluded were patients with known abnormal coagulation. We treated
      no patient for longer than 20 days. Before therapy, 6 months therapy began, and
      at the end of treatment, all patients underwent the following instrumental
      examinations: prothrombin and fibrinogen level measurements, liminal tonal
      audiometry, tympanometry, and assessment of otoacoustic emissions and otoacoustic
      products of distortion. Daily during the treatment, we monitored the patients by
      liminal tonal audiometry and assessment of otoacoustic emissions with linear
      click emission and otoacoustic products of distortion. We discharged patients
      when their audibility threshold stabilized. No patient experienced side effects
      due to the treatment, and functional results were excellent in all (even more so
      if compared with the protocols of therapy previously used for these kinds of
      diseases). The tissue plasminogen activator was used with remarkable success for
      the treatment of sudden hearing loss; this study shows remarkable success with a
      very low dose of rt-PA as compared to the standard dosage used for treatment of
      myocardial infarction.

PMID- 16639921
TI  - Seasonality in vestibular disorders.
AB  - Our objective in this study was to evaluate a causal relationship between
      vestibular pathological findings and climatic variations during the year (summer,
      autumn, winter, and spring). The study was conducted in a Brazilian clinic
      located in a tropical climate and having well-defined warm and cold weather. For
      this retrospective study, our outpatients were the subjects, and the diagnosis
      was made on the basis of clinical (ear, nose, and throat) and
      electronystagmographic evaluation. Data were collected, matched with the year's
      seasons, and analyzed for significance statistics. We found no significant
      differences among the illnesses in relation to the climatic seasons. We concluded
      that a correlation did not exist between annual seasons and vestibular disorders
      in our environment.

PMID- 16639922
TI  - [Reflection on the progress in cardiology as a scientific discipline].

PMID- 16639923
TI  - [Therapy of patients with heart failure--do we owe anything to our patients?].
AB  - In hardly any other field of treatment of a chronic disease more evident progress
      can be seen than in the therapy of hearth failure. Till the end of eighties of
      the previous century we were not able to influence the adverse development of the
      disease. With the critical prognosis, chronic heart disease represents more
      serious case than majority of tumours. In the meantime the only approach to
      decrease mortality has been modulation of the maladaptively activated regulatory
      mechanisms--the rennin, angiotensin, aldosteron axis and the sympatoadrenal
      system. During the previous decades we became witnesses of the development of new
      pharmacologic approaches aimed at the heart failure: New inotropics (e.g.
      lavosimendan and pomobendan) have been introduced, effects of anti-arrhythmiatics
      (amiodaron, dronedaron and others) and metabolically active drugs (trimetazidine,
      ranolazine and others) has been tested as well as methods decreasing fluid
      retention (aquaarretics) has been used. It is too early to conclude that such
      ethiopathogenetical approach can decrease mortality or morbidity. Along with the
      advance of new possibilities to interfere directly with the pathogenesis of the
      heart failure, approaches aimed at the treatment of deteriorating processes have
      been developing: prothrombotic state, atherogenesis or complications of anaemia.

PMID- 16639924
TI  - [Permanent cardiostimulation in the treatment of heart failure].
AB  - Congestive heart failure is a major health problem reaching epidemic proportions
      in the industrialized world. Despite significant advances in medical therapy,
      prognosis still remains dim. Cardiac resynchronization therapy is a novel
      therapeutic approach in management of heart failure patients. Its goal is the
      restoration of an impaired cardiac synchrony, which can be found in high number
      of heart failure patients. Cardiac dyssynchrony is characterized by presence of
      intra and interventricular conduction delays. Cardiac synchrony can be regained
      by biventricular stimulation. The procedure consists of a special lead being
      inserted via coronary sinus to a suitable branch of cardiac veins of the left
      ventricle in addition to a lead in the right ventricle cavity and right atrium.
      Several clinical trials have demonstrated that cardiac resynchronization therapy
      improves functional status and quality of life in majority of patients, as well
      as renders a favourable impact on prognosis.

PMID- 16639925
TI  - [Contemporary prospects for the diagnostics and treatment of the chronic
      pulmonary hypertension].
AB  - Pulmonary hypertension is defined as the rise of mean pressure in the pulmonary
      artery over 25 mmHg at rest or over 30 mmHg during activity with accompanying
      increase of pulmonary vascular resistance over 3 WU (Wood's unit). According to
      the recent WHO classification from 2003 pulmonary hypertension can be categorized
      as pulmonary arterial hypertension, pulmonary venous hypertension, hypoxic
      pulmonary hypertension, chronic thromboembolic pulmonary hypertension and
      pulmonary hypertension from other causes. Because symptoms of the pulmonary
      hypertension are non-specific, the diagnosis is frequently late. Patients with
      higher risk of pulmonary hypertension require frequent echocardiographic
      examination. Treatment of the pulmonary hypertension is rather complex and
      economically demanding. It should be therefore centralized in specialized units.
      Decision on the pharmacotherapy is based on the acute pulmonary vasodilatation
      test. Only patients with the positive test (10% of patients) are indicated to the
      treatment with calcium channel blockers. In case of negative test, the treatment
      of choice in NYHA III stadium is bosentam per orally, in the NYHA IV stadium it
      is epoprostenol intravenously. In patients with chronic thromboembolic pulmonary
      hypertension, organized thrombotic material should be surgically removed together
      with the layer of the pulmonary artery (pulmonary endarterectomy) after preceding
      anticoagulation treatment lasting at least three months. Pulmonary hypertension
      center of the Cardiocenter of the General teaching hospital is the only unit in
      the Czech Republic which beside the complex therapy of the pulmonary arterial
      hypertension can employ also the surgical treatment of the chronic thromboembolic
      pulmonary hypertension.

PMID- 16639926
TI  - [Current approach to the diagnostics and therapy of acute coronary syndromes].
AB  - The aim of this review is to provide a comprehensive actual overview of the
      current approach to acute coronary syndromes diagnostics, therapeutics and
      secondary prevention. Authors stress early diagnosis, risk stratification,
      indication and timing of interventional therapy. It is not an intention to
      provide detailed description of all clinical studies implemented recently in the
      field of acute coronary syndromes.

PMID- 16639927
TI  - [Role of Doppler echocardiography in the diagnostics and therapy of hypertrophic
      cardiomyopathy].
AB  - Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic
      heart disease. HCM is caused by mutations of genes encoding sarcomeric
      contractile proteins and it is characterized by heterogeneous pattern of left
      ventricular hypertrophy with dynamic obstruction of left ventricular outflow
      tract. HCM is associated with both impaired left ventricular contractility and
      diastolic function. Using Doppler echocardiography, we are able to assess left
      ventricular diastolic function and measure left ventricular outflow gradient.
      Tissue Doppler imaging of mitral annulus is able to discriminate genotype
      positive patients which allows us to improve diagnostic sensitivity of
      echocardiography. The Tei index is a new Doppler index, combining systolic and
      diastolic time intervals as an expression of global myocardial performance
      ("index of myocardial performance"). Non-pharmacologic treatment of obstructive
      HCM (alcohol septal ablation) is associated with improvement of Tei index.
      Doppler echocardiography is an indispensable tool in the management of HCM.

PMID- 16639928
TI  - [Mortality downtrend stopped during previous years].
AB  - In the nineties of the previous century the overall and cardiovascular mortality
      significantly decreased. It was probably caused by positive changes in the food
      habits. However, during the last five years the mortality decrease has stopped
      despite of the further progress of medical care. Main risk factors of
      atherosclerosis have not been developing as favourable as they were at the
      beginning of nineties. It is partly due to less appropriate nutrition in
      comparison with primary countries of the European Union and the smoking habits.

PMID- 16639929
TI  - [Aristoteles redivivus or small repetitorium of Aristotelian methodology
      regarding problems of psychosomatic medicine].
AB  - Present-day biological medicine has not reconciled the modern heritage of
      mechanistic conception of causality, which in many aspects limits the diagnostic
      and therapeutic potential of contemporary physicians. If such reduced principle
      of causality is confronted with Aristotelian conception of four types of disease
      causes and with the possibility to use it in the study of life nature (and
      therefore also in medicine), non-trivial differences will be revealed, which can
      at least bring some inspiration to present day physicians. The contemporary
      psychosomatically thinking physicians are in a similar position from which
      Aristotle criticized his foregoers for insufficient explanation of the principle
      of cause and effect. Medical doctors have many common points with Aristotle and
      that is why it is possible to speak, with certain hyperbole, about renewal of
      Aristotelian conceptions in some of the new trends of contemporary medicine,
      where the present-day mechanistic mentality is replaced with ecosystematic
      thinking.

PMID- 16639930
TI  - [Hope for patients with rare diseases--"orphan" drugs].
AB  - Rare diseases are defined as those affected less than five in every 10 000 person
      in European Union. The purpose of this paper is to present activities, which make
      possible to stimulate research development and marketing of appropriate medicine
      for tretment of rare disease, named "Orphan" medicinal products. EU "Orphan"
      medicinal products legislation which entered into force in April 2000 is
      described. Definition of "Orphan" medicinal products as well as the procedure of
      designation and placing the products into the Community register is presented.
      Those incentives to industry are described, which are already five years very
      well implemented oh the European level mostly on the pre-authorisation phase of
      "Orphan" medicinal products development, but also in the registration process as
      well as the post-authorisation phase. Finaly, the first twenty "Orphan" medicinal
      products, which have been given positive opinion in the Community for the grant
      of a marketing authorisation till April 2005 are mentioned in this work. The real
      availability of "Orphan" medicinal products in the particular EU member states is
      analysed.

PMID- 16639931
TI  - [EBV quantification in children after allogeneic hematopoietic stem cell
      transplantation].
AB  - BACKGROUND: Patients undergoing allogeneic hematopoietic stem cell
      transplantation (AHSCT) are endangered by developing Epstein-Barr virus-related
      post-transplant lymfoprolipherative disease (EBV-LPD). The aims of the study were
      to retrospectively characterise the viral loads in four patients who died of this
      complication, and to test possible risk factors for EBV reactivation in a
      prospectively observed cohort of children after AHSCT. METHODS AND RESULTS:
      Serial DNA samples extracted from whole blood from four patients who died of post
      transplant EBV-LPD in year 2000 were retrospectively analysed for EBV load using
      quantitative real-time PCR. First detection of EBV activation preceded death by
      24-91 days. All four patients exceeded a viral load of one million EBV copies per
      100,000 human genome equivalents. A cohort of 72 children undergoing AHSCT
      between 2001-2004 was prospectively followed-on using the same quantification
      method from regularly obtained samples of whole blood, and clinical and
      laboratory data were recorded on a weekly basis, totalling at 3,896 person-weeks
      of observation. Approximately one half of the cohort experienced at least one
      episode of EBV reactivation during the first 100 days after AHSCT, four of the
      episodes being accompanied with viral loads higher than our provisional threshold
      of 10,000 copies per 100,000 human genome equivalents. Three of the four patients
      developed EBV-LPD and were successfully treated by intravenous administration of
      anti-CD20 antibody. Testing of possible clinical and laboratory predictors of EBV
      reactivation did not reveal any clinically useful association. CONCLUSIONS: The
      cornerstone of predicting EBV-LPD in AHSCT is a regular monitoring of EBV viral
      load using quantitative methods. Using this strategy with a threshold of 10,000
      EBV copies per 100,000 human genome equivalents was proved to be effective, as
      shown by no death of EBV for the study period, compared to four cases in the year
      before the quantitative monitoring.

PMID- 16639932
TI  - [Pulmonary endarterectomy--the surgical treatment of chronic thromboembolic
      pulmonary hypertension].
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) in indicated
      cases can be successfully treated by the endarterectomy of pulmonary arteries
      (PEA). Symptomatically not treated CTEPH has highly unfavourable prognosis. Five
      years survival of patients with mean pulmonary pressure over 50 mmHg is only 10%.
      PEA was not available in the Czech Republic till 2004, when PEA program was
      initiated it the Cardiocenter of the General teaching hospital in Prague in
      collaboration with leading clinics in that field (Prof. Mayer, University of
      Mainz, BRD). METHODS AND RESULTS: Up-to-date surgical technique, which in various
      modifications has been used at majority of clinics, was elaborated by Jamieson
      and Daily at University of California in San Diego. It is based on reverse
      endarterectomy performed during complete circulatory arrest with brain protection
      by deep hypothermia. Till September 2005 twelve patients were operated with zero
      mortality. In one patient a suture of atrial septum defect was necessary to
      perform along. Average time of the circulatory arrest was 45 minutes; duration of
      the extracorporal circulation was 334 minutes. Average duration of the operation
      was 450 minutes. Duration of the mechanical ventilation was in average 45.5
      hours. After one month already haemodynamic parameters (mPA, CI, PVR)
      significantly improved or normalized and the average length in the test of six
      minutes walking increased by 132 meters. CONCLUSION: PEA represents a treatment
      method for patients with CTEPH and surgically accessible pulmonary artery
      obstruction. Centralized care of those patients is a rational necessity enabling
      to get maximum experience with complicated diagnostics and treatment of those
      patients. Multidisciplinary collaboration is the essential condition for the
      success of the program.

PMID- 16639933
TI  - [Parental smoking and exposure of pre-school children to tobacco smoke].
AB  - BACKGROUND: During studies on the health of children aged 3 or 4.5 years in
      Teplice and Prachatice districts of the Czech Republic, we focused also on the
      extent of smoking in the families and exposure of children to environmental
      tobacco smoke. METHODS AND RESULTS: In 1128 questionnaires administered to
      mothers of children born in 1994-1998, 35.6% of mothers indicated that they
      smoked and 48.9% of fathers/partners (N = 1075) were smokers. Including other
      family members, there were 41.6% families without any smoker, 30.1% of families
      with one smoker and 24% families with two smokers (out of 1061 households). Urine
      samples of 523 pairs of mothers and children (aged 4.5 years) were assayed for
      cotinine using a RIA radioimmunoassay. Concentration of cotinine was higher than
      500 ng cotinine/mg creatinine (the cut-off value for smoking) in 199 of 523
      mothers (38%). Exposure of children to environmental tobacco smoke (cotinine
      levels over 20ng/mg creatinine) was detected in 48.2% of 523 children. There were
      more children with cotinine levels over 20 ng in Teplice (59.2% of 287 children)
      than in Prachatice district (34.7% of 236 children). CONCLUSIONS: Cotinine levels
      in child's urine were significantly positively associated with maternal cotinine
      levels as well as with smoking of mother and father, and were lower in children
      visiting kindergarten.

PMID- 16639934
TI  - [Methylene blue in the therapy of vasoplegic syndrome after cardiac surgery
      procedure].
AB  - Vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass is severe
      complication with high morbidity and mortality. Without appropriate therapy the
      syndrome advances to the shock state with subsequent multiorgan failure. Basic
      haemodynamic parameters of vasoplegic syndrome include low systemic vascular
      resistance with severe hypotension, tachycardia, and normal or increased cardiac
      output and low filling pressures. In therapy norepinephrine and vasopressin or
      its analogues are used. Methylene blue is other therapeutic option. The case of
      successful application of methylene blue for the treatment of vasoplegic syndrome
      is presented.

PMID- 16639935
TI  - [Larva migrans cutanea].
AB  - A case of rare skin disease in Czech Republic caused by nematode larva is
      presented. The disease is most frequently caused by Ankylostoma brasiliensis and
      was imported from Brazil. It was successfully treated by peroral therapy with
      albendazol.

PMID- 16639936
TI  - [Purkynje fibers of the heart conduction system--history and the present time].
AB  - It has been 160 years now since Purkynje published the finding of conduction
      fibers in the heart in Archiv f. Anatomie u. Physiologie and it has been 166
      years since his publication in polish version. Already during Purkynje's life,
      some anatomists had solved the morphology of these fibers but nobody at that time
      knew of what great physiological and medical importance this discovery would be
      for medicine. It was seen as late as in the 20th century and in contemporary
      times. Purkynje's work indicated the cascade of these discoveries, which were
      leading in the beginning of the previous century to the formulation of the basic
      scheme of the conduction system. Purkynje fibers or Purkynje cardiomyocytes are
      part of the whole complex of the cardiac conduction system which today is
      classified as specific heart muscle tissue, being responsible for the generation
      of the heart impulses. From the point of view of ultrastructural composition, the
      cells of different parts of the cardiac conduction system are partly similar. In
      contrast to the heart contractile cardiomyocytes, the cells of the cardiac
      conduction system including Purkynje fibers have a small amount of
      myofibrils,small mitochondrias, light cytoplasm and a higher glycogen content,
      but no T-tubular system. They can be detected with some morphological methods.
      Nevertheless the cells of the conduction system are not completely uniform. They
      differ in size, number of nexuses-gaps and intercalar discs in individual parts
      of the conduction system. Nevertheless, these specialized cells work as a whole
      unit. Nowadays, the morphology research of all the parts of cardiac conduction
      system, including Purkynje fibers, is focused on ultrastructural, histochemical
      and genetical problems. The question is, wheather with future gene/cell therapy
      disturbances of the conduction system such as arrythmias, can be prevented and
      cured by replacing the electrical pacemakers with biological ones. If Jan
      Evangelista Purkynje lived today, he would be surprised but surely delighted with
      the high degree of research concerning his discovery and its clinical
      application.

PMID- 16639937
TI  - [Impact factor in the view of Milan Spala].

PMID- 16639939
TI  - Antimicrobial susceptibilities of thermophilic Campylobacter from humans, swine,
      and chicken broilers.
AB  - The aim of this study was to evaluate the incidence and the distribution of
      antimicrobial resistance, and the presence of genetic determinants of resistance,
      in Campylobacter recovered from swine, poultry, and human populations in Quebec.
      Minimum inhibitory concentrations (MICs) of 10 antimicrobial agents were
      determined by the agar dilution technique. Polymerase chain reaction (PCR) was
      used to detect the tetO determinant, and mutations in gyrA were analyzed by
      sequencing and by mismatch amplification mutation assay (MAMA) PCR. Among C. coli
      isolates from pigs, the rates of resistance were high, at 59% for clindamycin,
      61% for erythromycin, 67% for streptomycin, and 68% for tetracycline; isolates
      from chicken broilers were mainly resistant to streptomycin and tetracycline,
      with a rate of 50% for each; and 56% of the isolates from humans were resistant
      to tetracycline. The rates of resistance among C. jejuni isolates were low except
      for tetracycline (39% and 67% in humans and broilers, respectively). The tetO
      determinant was identified among both tetracycline-resistant and tetracycline
      susceptible Campylobacter isolates from swine. Sequencing analysis showed that
      64% and 100% of ciprofloxacin-resistant C. coli isolates from swine and humans,
      respectively, had the mutation Thr-86-->Ile, which is associated with quinolone
      resistance. The MAMA PCR gave identical results. Further analyses need to be done
      in order to detect other genetic determinants of tetracycline resistance.

PMID- 16639940
TI  - Development of a technique for serial bilateral renal biopsy in steers.
AB  - A biopsy procedure was developed to provide serial kidney samples from standing
      steers. Ten clinically normal steers were given intramuscular injections of
      gentamicin sulfate, 4 mg/kg body weight. Renal biopsy was performed at 5 separate
      times. After feed was withheld for 24 h, laparoscopic surgery was performed in
      standing stocks. Acepromazine, xylazine, and butorphanol were used for sedation
      and analgesia, and 2% lidocaine was used for local anesthesia. Two incisions
      approximately 2 cm long were made in the paralumbar fossa to allow for trocar
      introduction. The abdomen was insufflated with CO2 and, with endoscopic guidance,
      a biopsy forceps used to remove a kidney sample 2 to 3 mm in diameter, by either
      a left or a right abdominal approach. Each operation was recorded on videotape,
      and images were also captured with a digital medical device system. Respiration,
      heart rate, temperature, appetite, attitude, and postural positions were
      evaluated at 12, 24, 48, and 72 h after surgery. The 51 laparoscopic procedures
      provided 48 renal samples (approximately 100 mg each). The 1st and 2nd samples
      were from the right kidney, and the 3rd sample was from either the left or the
      right kidney; the 4th and 5th samples were from the left kidney. Adhesions made
      an approach from the right side difficult for the 3rd sample. No clinical changes
      were observed in 9 steers after the procedure. One steer died after the 3rd
      procedure owing to hemorrhage.

PMID- 16639941
TI  - Molecular characterization of Streptococcus suis strains by 16S-23S intergenic
      spacer polymerase chain reaction and restriction fragment length polymorphism
      analysis.
AB  - We developed a new molecular method of typing Streptococcus suis based on
      polymerase chain reaction (PCR) amplification of a large fragment of rRNA genes,
      including a part of the 16S and 23S genes and the 16S-23S intergenic spacer
      region (ISR), followed by restriction fragment length polymorphism (RFLP)
      analysis with RsaI or MboII endonuclease. The 16S-23S ISRs of 5 S. suis isolates
      were sequenced and compared. Size and sequence polymorphisms were observed
      between the S735 reference strain and the 4 wild-type strains. The genetic
      relationships between 138 independent S. suis strains belonging to various
      serotypes, isolated from swine or human cases, were determined. The
      discriminatory power of the method was > 0.95, the threshold value for
      interpreting typing results with confidence (0.954 with RsaI and 0.984 with RsaI
      plus MboII). The in vitro reproducibility was 100%. The strains isolated from
      humans were less genetically diverse than the strains isolated from pigs. For the
      first time, 2 molecular patterns (R6, M9) were significantly associated with S.
      suis serotype 2 strains. This genetic tool could be valuable in distinguishing
      individual isolates of S. suis during epidemiologic investigations.

PMID- 16639942
TI  - Characterization of antimicrobial resistance of Salmonella Newport isolated from
      animals, the environment, and animal food products in Canada.
AB  - Multi-drug-resistant (MDR) Salmonella enterica serovar Newport strains are
      increasingly isolated from animals and food products of animal origin and have
      caused septicemic illness in animals and humans. The purpose of this study was to
      determine the occurrence and the epidemiologic, phenotypic, and genotypic
      characteristics of S. Newport of animal origin that may infect humans, either via
      the food chain or directly. During the 1993-2002 period, the Office International
      des Epizooties Reference Laboratory for Salmonellosis in Guelph, Ontario,
      received 36 841 Salmonella strains for serotyping that had been isolated from
      animals, environmental sources, and food of animal origin in Canada. Of these,
      119 (0.3%) were S. Newport. Before 2000, none of 49 S. Newport strains was
      resistant to more than 3 antimicrobials. In contrast, between January 2000 and
      December 2002, 35 of 70 isolates, primarily of bovine origin, were resistant to
      at least 11 antimicrobials, including the extended-spectrum cephalosporins. The
      blaCMY-2', flo(st'), strA, strB, sulII, and tetA resistance genes were located on
      plasmids of 80 to 90 MDa that were self-transmissible in 25% of the strains.
      Conserved segments of the integron 1 gene were found on the large MDR-encoding
      plasmids in 3 of 35 strains additionally resistant to gentamicin and
      spectinomycin or to spectinomycin, sulfamethoxazole-trimethoprim, and
      trimethoprim. Resistance to kanamycin and neomycin was encoded by the aphA-1
      gene, located on small plasmids (2.3 to 6 MDa). The increase in bovine-associated
      MDR S. Newport infections is cause for concern since it indicates an increased
      risk of human acquisition of the infection via the food chain.

PMID- 16639943
TI  - Influence of the genotype of Staphylococcus aureus, determined by pulsed-field
      gel electrophoresis, on dry-period elimination of subclinical mastitis in
      Canadian dairy herds.
AB  - By combining information from 2 databases, we investigated the possibility of an
      association between the genotype of Staphylococcus aureus causing bovine
      intramammary infection and dry-period cure of subclinical infection. The 1st
      database contained bacteriologic and cow data from a field study evaluating the
      efficacy in such infections of a new intramammary dry-cow therapy (DCT)
      containing tilmicosin phosphate, in comparison with a commercially available DCT
      containing benzathine cloxacillin. Isolates of S. aureus from that study were
      frozen and later independently analyzed by pulsed-field gel electrophoresis
      (PFGE) and macrorestriction DNA fingerprinting. The molecular information,
      summarized and published elsewhere, constituted the 2nd database. Data from 121
      subclinically infected quarters of 92 cows from 40 herds were studied by
      univariate and multivariable regression analysis. Infection by an isolate of PFGE
      lineage group D was more likely than infection by an isolate of group A or F to
      be cured (P < 0.05). Cows infected by lineage group D had a higher linear somatic
      cell count score (LS) from the last Dairy Herd Improvement test before the dry
      period than did cows infected by the other lineage groups (P = 0.04). Although
      the probability of cure was significantly lower for cows with an LS at or above
      the mean of 5.7 for the study population (P = 0.05), when such a cow was infected
      with lineage group D, cure was significantly more likely (P < 0.001) than when it
      was infected by another lineage group. Significantly more (P = 0.02) of the
      infections treated with tilmicosin (74%) than of those treated with benzathine
      cloxacillin (53%) were cured, and significantly more (P = 0.05) of the infections
      by group D (81%) than of those by group A (57%) or group F (54%) were cured.
      However, there was no difference in cure rate for any PFGE genotype when
      tilmicosin phosphate was administered; when benzathine cloxacillin was
      administered, 87% of lineage group D isolates were eliminated, as compared with
      46% of group A and 33% of group F isolates (P < 0.05). This research demonstrates
      that certain genotypes of S. aureus may naturally elicit a greater inflammatory
      response, yet be more susceptible to elimination by antibiotics in the dry
      period, than other genotypes.

PMID- 16639944
TI  - Challenge with Bovine viral diarrhea virus by exposure to persistently infected
      calves: protection by vaccination and negative results of antigen testing in
      nonvaccinated acutely infected calves.
AB  - Calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV)
      represent an important source of infection for susceptible cattle. We evaluated
      vaccine efficacy using calves PI with noncytopathic BVDV2a for the challenge and
      compared tests to detect BVDV in acutely or transiently infected calves versus PI
      calves. Vaccination with 2 doses of modified live virus vaccine containing BVDV1a
      and BVDV2a protected the calves exposed to the PI calves: neither viremia nor
      nasal shedding occurred. An immunohistochemistry test on formalin-fixed ear
      notches and an antigen-capture enzyme-linked immunosorbent assay on fresh notches
      in phosphate-buffered saline did not detect BVDV antigen in any of the acutely or
      transiently infected calves, whereas both tests had positive results in all the
      PI calves.

PMID- 16639945
TI  - Effect of group size and structure on the welfare and performance of pregnant
      sows in pens with electronic sow feeders.
AB  - Pregnant sows were housed in dynamic, twice-mixed, and static groups of different
      sizes in pens with electronic sow feeders (ESFs) to study the effect of group
      size and structure on sow welfare and performance. The total injury score (TIS)
      was significantly higher (P < 0.05) in the dynamic group than in the other groups
      in general and 2 wk after mixing. The salivary cortisol concentrations were
      similar in the 3 groups. The frequency of queuing was significantly higher (P <
      0.05) in the twice-mixed group and the frequency of nonagonistic social
      interactions significantly lower (P < 0.05) in the dynamic group. The total
      number of aggressive acts was positively and significantly correlated (P < 0.05)
      with the frequency and duration of queuing in all the groups. Farrowing
      performance and longevity did not differ between the groups. The higher TIS and
      lower number of nonagonistic social interactions indicated that welfare was
      compromised in the dynamic group as compared with the other groups.

PMID- 16639946
TI  - Evaluation of ionized and total serum magnesium concentrations in hyperthyroid
      cats.
AB  - Hyperthyroidism can increase the renal excretion of magnesium and thus cause
      hypomagnesemia in various species. Anaerobically collected blood samples from 15
      hyperthyroid and 40 normal, healthy cats were analyzed with an ion-selective
      electrode analyzer and a serum biochemical analyzer. There was no significant
      difference in ionized or total serum magnesium concentration between the 2
      groups, but there was a significant difference (P = 0.004) in the ratio of
      ionized to total serum magnesium concentrations between the healthy cats and the
      hyperthyroid cats with thyroxine (T4) concentrations at or above the median.
      There was a significant correlation (r = 0.894, P = 0.000) between the ionized
      and total magnesium concentrations in the hyperthyroid cats. The hyperthyroid
      cats had a significantly lower (P = 0.003) total serum protein concentration than
      the healthy cats. A significant negative correlation (r = -0.670, P = 0.006) was
      detected between the ionized magnesium and logarithmically transformed total T4
      concentrations in the hyperthyroid cats, which suggests that the severity of
      hyperthyroidism may contribute to a decrease in the ionized magnesium
      concentration.

PMID- 16639947
TI  - Successful engraftment of cultured autologous mesenchymal stem cells in a
      surgically repaired soft palate defect in an adult horse.
AB  - The objective of this study was to graft autologous mesenchymal stem cells (MSCs)
      at the site of surgical repair of a soft palate defect in an adult horse in an
      attempt to improve wound healing and to investigate whether the transplanted MSCs
      would integrate into the soft palate structure and participate in regeneration.
      Bone marrow was collected from an adult horse with a full-thickness soft palate
      defect. The MSCs were isolated, cultured in monolayers, and labeled with 5-bromo
      2-desoxymidine (BrdU) and chloromethylbenzamido-DiI-derived (cm-DiI) before
      transplantation. The soft palate defect was repaired by mandibular symphysiotomy,
      and the labeled MSCs were injected into the repaired soft palate. Postmortem
      examination revealed that 90% of the soft palate defect had been sutured.
      Staining by BrdU and cm-DiI was intense in the soft palate tissue. Labeled MSCs
      were detected in tissue slices from the injection sites. The cells were organized
      in a manner similar to that in native soft palate tissue, indicating successful
      engraftment.

PMID- 16639948
TI  - Clinical and genetic assessments of hip joint laxity in the Boykin spaniel.
AB  - Canine hip dysplasia (CHD) is characterized by a malformation of the hip joint
      that leads to joint laxity and consequential degenerative joint disease. The most
      widely used method for diagnosis of CHD is the ventrodorsal hip-extended
      radiologic view, commonly referred to as the Orthopedic Foundation for Animals
      (OFA) method. The method of the University of Pennsylvania Hip Improvement
      Program (PennHIP), an alternative technique that is based on hip joint laxity,
      provides a quantitative assessment, the distraction index (DI), of the likelihood
      of the development of CHD because of increased laxity in the hip joint. Linear
      regression analysis showed that, across many breeds of dog, the incidence of CHD,
      as defined by the OFA, is positively correlated with the mean DI, the
      determination coefficient (r2) being 26%. We used families of Boykin spaniels
      (BSs) to determine the level of joint laxity in the breed and to conduct an
      initial whole-genome screening to identify markers that co-segregate with
      increased joint laxity. Although there was a positive correlation between the
      incidence of hip dysplasia and increased joint laxity, we did not find
      significant linkage in the 28 BSs that underwent genotyping, likely owing to the
      small size of the pedigree.

PMID- 16639949
TI  - Quantification of cortisol, cortisol immunoreactive metabolites, and
      immunoglobulin A in serum, saliva, urine, and feces for noninvasive assessment of
      stress in reindeer.
AB  - This study was designed to develop reliable methods for quantification of
      cortisol and cortisol immunoreactive metabolites (C-CIM) and immunoglobulin A
      (IgA) in reindeer serum, saliva, urine, and feces as tools for the objective
      noninvasive assessment of well-being and immunocompetence in reindeer. Although C
      CIM was readily quantifiable by radioimmunoassay in serum, urine, and feces, the
      levels in saliva samples were low, rendering quantification unreliable. Whereas
      IgA concentrations were high in feces samples, they were much lower, albeit
      quantifiable, in serum and urine; the levels in saliva samples were too low for
      quantification with the use of an enzyme-linked immunosorbent assay that we
      developed. Further studies are in progress to validate the usefulness of fecal
      levels of C-CIM and IgA in the assessment of welfare in reindeer.

PMID- 16639950
TI  - Evaluation of porcine ileum models of enterocyte infection by Lawsonia
      intracellularis.
AB  - The early interaction of Lawsonia intracellularis with host cells was examined
      with the use of porcine ileum models. Two conventional swine were anesthetized,
      and ligated ileum loops were prepared during abdominal surgery. The loops were
      inoculated with 108 L. intracellularis or saline. After 60 min, samples of each
      loop were processed for routine histologic and electron microscopic study.
      Histologic and ultrathin sections of all the loops appeared normal, with no
      apposition of bacteria and host cells or bacterial entry events in any loop.
      Portions of ileum from a single gnotobiotic piglet were introduced as xenografts
      into the subcutis of each flank of 5 weaned mice with severe combined
      immunodeficiency disease. After 4 wk, 108 L. intracellularis were inoculated into
      each of 4 viable xenografts with a sterile needle; the other 3 viable xenografts
      received saline. Histologic and ultrathin sections of all the xenografts 3 wk
      after inoculation showed relatively normal porcine intestinal architecture, with
      normal crypts, crypt cell differentiation, and low villous structures; the
      xenografts treated with the bacteria also showed intracytoplasmic L.
      intracellularis within crypt and villous epithelial cells. Thus, entry of L.
      intracellularis into target epithelial cells and multiplication may not be
      sufficient alone to directly cause cell proliferation. A proliferative response
      may require active division of crypt cells and differentiation in conjunction
      with L. intracellularis growth.

PMID- 16639951
TI  - Mater Central Queensland's log of claims.

PMID- 16639952
TI  - The nursing shortage.

PMID- 16639953
TI  - Nursing against the odds.

PMID- 16639954
TI  - Under pressure--EDs in the spotlight.

PMID- 16639955
TI  - Respect, recognition and reward: defining nursing.

PMID- 16639956
TI  - What impact will the public sector wage proposal of 23% have on private
      hospitals?

PMID- 16639957
TI  - Professional indemnity insurance.

PMID- 16639958
TI  - Overseas worker visas skyrocket out of control under Howard government.

PMID- 16639959
TI  - Employers win right to undercut minimum wage in new IR laws: regional workers
      most at risk.

PMID- 16639960
TI  - Palliative care. First and foremost the domain of family physicians.

PMID- 16639961
TI  - Does epidural analgesia increase rate of cesarean section?

PMID- 16639962
TI  - Keeping your sunny side up. How sunlight affects health and well-being.

PMID- 16639963
TI  - Concerns about what constitutes clinical evidence.

PMID- 16639964
TI  - Family physicians are generalists!

PMID- 16639965
TI  - Some positive steps for preventive health.

PMID- 16639966
TI  - How do I tell you that you are dying?

PMID- 16639967
TI  - Major malformations with valproic acid.
AB  - QUESTION: Increasing numbers of pregnant patients are treated with valproic acid,
      not just for epilepsy, but also for psychiatric conditions. Are there teratogenic
      risks other than the risk of spina bifida? ANSWER: It has now become evident that
      valproic acid might cause more than just neural tube defects (NTDs). In a
      systematic review of all cohort studies intended to answer this question, higher
      rates of major malformations (and not just NTDs) were found in most studies. The
      calculated relative risk was 2.59 when compared with other antiepileptic drugs
      and was 3.77 when compared with risk in the general population. There is
      compelling evidence that the risk is dose dependent. The risks appear to begin
      increasing at doses of 600 mg/d and to become more prominent at doses above 1000
      mg/d.

PMID- 16639968
TI  - Metformin and type 2 diabetes mellitus.

PMID- 16639969
TI  - Practice tips. Chart audits in my practice.

PMID- 16639970
TI  - Preventing recurrent ulcer bleeding. Switch from acetylsalicylic acid to
      clopidogrel or add esomeprazole?

PMID- 16639971
TI  - An approach to advance care planning in the office.
AB  - OBJECTIVE: To outline how advance care planning is a process of communication
      among patients, their families, and health care providers regarding appropriate
      care for patients when they are no longer able to make decisions for themselves.
      SOURCES OF INFORMATION: Level I evidence supports systematic implementation of
      advance care planning under controlled circumstances, such as in institutions.
      Level II evidence supports exploring factors that determine treatment preferences
      and change treatment preferences and other factors that complicate the process of
      end-of-life decision making. Level III evidence supports the approach to advance
      care planning in the office described in this article. MAIN MESSAGE: Family
      physicians can help prevent the suffering of patients with chronic illnesses by
      facilitating discussion of end-of-life issues. The approach suggested in this
      article will help reduce avoidance of the issues and minimize the difficulty of
      discussing issues crucial to patients and their families. CONCLUSION: Advance
      care planning can prevent suffering and enable patients to receive care congruent
      with their goals at the end of their lives. Family physicians can be key to
      facilitating this process.

PMID- 16639972
TI  - Selected topics of hypoglycemia care.
AB  - OBJECTIVE: To review 4 topics in hypoglycemia (HoG) care: diagnosis,
      circumstances predisposing to HoG, risk of adverse effects, and prevention.
      QUALITY OF EVIDENCE MEDLINE: was searched using the words hypoglycemia and
      diabetes mellitus. Other relevant sources were hand searched. Evidence was mostly
      level III and IV from consensus, from observation, and from the author's clinical
      experience. MAIN MESSAGES: Hypoglycemia can be diagnosed using clinical criteria
      or using a glucometer; it cannot be diagnosed after death. Capillary blood
      glucose testing for HoG is required only for patients taking insulin and insulin
      secretagogues. With intensified treatment of diabetes, a greater incidence of HoG
      is inevitable. Chronic morbidity and mortality resulting from HoG are believed to
      be rare. There are no reliable data on HoG-related mortality for idiopathic or
      accidental sudden death. Interventions by friends, family, colleagues, and
      teachers can prevent HoG. CONCLUSION: Clinical diagnosis of HoG deserves greater
      emphasis; when patients are unaware of having HoG, physicians must rely on blood
      glucose testing. Patients not taking insulin or insulin secretagogues need
      neither fear nor test for HoG. The risk of HoG should not preclude efforts to
      achieve best possible control of blood sugar. Patients with unstable cardiac
      arrhythmias, drivers of motor vehicles, and those in high-risk industrial
      occupations require special vigilance for HoG.

PMID- 16639973
TI  - Emergency cardiovascular care guidelines 2005.

PMID- 16639974
TI  - Residents' page. Reflections on dying.

PMID- 16639975
TI  - Phenotypes of aquaporin mutants in genetically altered mice.
AB  - The ability to move water across lipid membranes is crucial for nutrient intake,
      energy generation, waste excretion, and a myriad of other functions associated
      with life. Aquaporins, a family of integral membrane proteins, are now recognized
      as the channels responsible for transporting hydrophilic molecules, including
      water, across relatively impervious, hydrophobic cell membranes. A tremendous
      amount of work has been published on characterizing these proteins, which have
      been found in all bacteria, yeast, plants, and animals examined to date. In
      addition, an increasing number of mouse models with genetically altered aquaporin
      expression are being reported. This article will briefly review the basic
      biochemistry of aquaporins and then evaluate the use (and misuse) of mice in the
      quest for understanding the comparative pathophysiology of aquaporins in humans.

PMID- 16639976
TI  - Feasibility and limits of an orthotopic human colon cancer model in nude mice.
AB  - We sought to develop an accurate colorectal cancer model in nude mice with stable
      local growth, tumor cell dissemination, and reproducible metastatic capacity. To
      this end, we orthotopically transplanted histologically intact human colorectal
      cancer tissue from 10 human patients into nude mice. After successful local tumor
      growth, tumor tissues were retransplanted as many as 9 times in serial passage.
      All specimens were transplanted using microsurgical techniques. Histologic,
      immunohistochemical, and polymerase chain reaction techniques were used to
      determine tumor growth rates and kinetics, development of regional lymph node and
      distant hepatic metastases, and the induction of minimal residual disease (MRD).
      Stable local tumor growth rates with variable growth kinetics were detected in
      73.4% of all mice. The lymph node and hepatic metastasis rates were low, at 18.4%
      and 4.9%, respectively. MRD, as reflected by CK20 positivity of the bone marrow
      in animals with lymph node and hepatic metastases, was present in 22.2%. The
      orthotopic colorectal cancer model described here is feasible for the induction
      of reproducible local tumor growth but is limited by variable growth kinetics and
      the low rate of lymph node and hepatic metastases. Cytokeratin-positive cells
      indicative of MRD could be detected in the bone marrow of approximately 25% of
      the nude mice with metastases. The observed induction of MRD after orthotopic
      implantation of intact human colon cancer in animals with lymph node and hepatic
      metastases might be improved if established colon cancer cell lines were used.

PMID- 16639977
TI  - Occurrence of Helicobacter species other than H. hepaticus in laboratory mice and
      rats in Sweden.
AB  - The aim of this study was to determine which Helicobacter species other than H.
      hepaticus colonize laboratory mice and rats in Sweden. We analyzed 63 intestinal
      samples from mice and 42 intestinal samples from rats by partial 16S rDNA
      sequence analysis. Previously these samples had been found positive for
      Helicobacter species but negative for H. hepaticus in a polymerase chain reaction
      screening assay at the National Veterinary Institute in Sweden. H. ganmani, H.
      typhlonius, H. rodentium, an uncharacterized Helicobacter species ('hamster B'),
      and a possibly novel species were detected in mice. The possibly novel species
      was most closely related to H. apodemus strain YMRC 000216 (98.3% sequence
      similarity). Two different Helicobacter species were detected in rats: H. ganmani
      and H. rodentium. H. ganmani colonization of rats has not previously been
      reported.

PMID- 16639978
TI  - Are repeated doses of buprenorphine detrimental to postoperative recovery after
      laparotomy in rats?
AB  - Buprenorphine is a widely used analgesic for relief of postoperative pain in
      rats. The effect of repeated doses of buprenorphine throughout the postoperative
      pain and stress response is unknown. This investigation tested the hypotheses
      that (a) daily analgesic doses of buprenorphine for 7 d ameliorate the stress
      response after laparotomy in rats and (b) preoperative buprenorphine better
      ameliorates the response than do peri- and postoperative administration.
      Postoperative effects on body weight, daily food and water consumption, and daily
      fecal and urinary outputs were monitored in groups of rats treated for 7 d with
      analgesic doses of buprenorphine initiated at different time points relative to
      the time of laparotomy. Analgesic doses of buprenorphine had no effect on the
      study parameters in healthy unoperated rats. Daily injection of buprenorphine
      delayed the time at which the preoperative body weight was restored without
      decreasing the postoperative changes in daily food consumption, water intake, and
      fecal and urinary outputs in the operated rats. The effects of daily analgesic
      doses of buprenorphine for 7 d on body weight, daily food, and water consumption,
      and fecal and urinary outputs were minimal and less statistically significant
      than the changes caused by surgery itself. However, this dosing regimen seems to
      delay the restoration of body weight after abdominal surgery in rats.

PMID- 16639979
TI  - Detection of systemic amyloidosis in the pig-tailed macaque (Macaca nemestrina).
AB  - Secondary amyloidosis is a progressive systemic disease for which there is no
      reliable diagnostic assay, preventive measure, or treatment. In an attempt to
      elucidate an antemortem diagnosis, 30 female pig-tailed macaques (Macaca
      nemestrina) at the Washington National Primate Research Center were surveyed for
      amyloidosis. Amyloid was demonstrated histologically in 47% (14 of 30) of the
      animals. The distribution and severity of amyloid deposition was variable.
      Affected animals had a mean age (+/-1 standard deviation) of 13.2 +/- 4.9 y,
      which was significantly greater than the mean age of unaffected animals (9.3 +/-
      4.1) y. Twelve tests were evaluated for detection of amyloidosis; the diagnostic
      value of each was determined through comparison of histologically positive and
      histologically negative animals. Diagnostic tests evaluated were endoscopic
      examination and biopsy of the stomach and colon, abdominal ultrasonography,
      hepatic radiology, serum amyloid A (SAA), endothelin 1, alpha-fetal protein,
      aspartate aminotransferase (AST), alanine aminotransferase, gamma
      glutamyltransferase (GGT), alkaline phosphatase, cholesterol, blood urea
      nitrogen, total bilirubin, C-reactive proteins, and erythrocyte sedimentation
      rate. Amyloidotic animals demonstrated a distinctive serologic profile: elevated
      SAA, GGT, and AST in combination with decreased total protein and albumin.
      Radiology demonstrated hepatomegaly in animals with hepatic amyloid deposition.
      In the absence of known infection or trauma, an amyloidotic serologic profile and
      radiologic hepatomegaly are consistent with systemic amyloidosis in M.
      nemestrina.

PMID- 16639980
TI  - Cortisol metabolism in the Bolivian squirrel monkey (Saimiri boliviensis
      boliviensis).
AB  - New World squirrel monkeys (Saimiri spp.) have high circulating cortisol levels
      but normal electrolytes and blood pressures. The goal of the present study was to
      gain insight into adaptive mechanisms used by Bolivian squirrel monkeys to
      minimize the effects of high cortisol on mineralocorticoid receptor (MR) activity
      and electrolyte and water balance. Aldosterone levels in serum from 10 squirrel
      monkeys were 17.7 +/- 3.4 ng/dl (normal range in humans, 4 to 31 ng/dl),
      suggesting that squirrel monkeys do not exhibit a compensatory increase in
      aldosterone. The squirrel monkey MR was cloned and expressed in COS-7 cells and
      found to have similar responsiveness to cortisol and aldosterone as human MR,
      suggesting that squirrel monkey MR is not inherently less responsive to cortisol.
      To determine whether altered metabolism of cortisol might contribute to MR
      protection in squirrel monkeys, serum and urinary cortisol and cortisone were
      measured, and a comprehensive urinary corticosteroid metabolite profile was
      performed in samples from anesthetized and awake squirrel monkeys. The levels of
      cortisone exceeded those of cortisol in serum and urine, suggesting increased
      peripheral 11beta-hydroxysteroid dehydrogenase 2 activity in squirrel monkeys. In
      addition, a significant fraction (approximately 20%) of total corticosteroids
      excreted in the urine of squirrel monkeys appeared as 6beta-hydroxycortisol,
      compared with that in man (1%). Therefore, changes in cortisol metabolism likely
      contribute to adaptive mechanisms used by Bolivian squirrel monkeys to minimize
      effects of high cortisol.

PMID- 16639981
TI  - Ovine intestinal adenocarcinomas: histologic and phenotypic comparison with human
      colon cancer.
AB  - Approximately 7% of old, unthrifty sheep (Ovis aries) in New Zealand have
      intestinal adenocarcinomas. To investigate whether these sheep might be used as a
      model of human colonic neoplasia, the biologic behavior and histologic appearance
      of ovine intestinal adenocarcinomas were compared with those reported for human
      colonic adenocarcinomas. We collected 50 intestinal tracts with grossly visible
      intestinal neoplasia from slaughtered sheep. Neoplasms were assessed using World
      Health Organization guidelines for assessment of human colonic adenocarcinomas.
      All ovine adenocarcinomas developed in the small intestine. In contrast, only 4%
      of human intestinal tumors develop at this location, whereas the majority develop
      in the colon. A visible polyp is present within 89% of human colonic
      adenocarcinomas, whereas polyps were present in only 46% of the ovine neoplasms.
      Intestinal wall infiltration by the neoplastic cells and rates of lymph node (84%
      in sheep; 61% in humans) and distant (52% in sheep; 17% in humans) metastases
      were comparable between ovine and human adenocarcinomas. However, ovine
      adenocarcinomas developed more peritoneal and fewer hepatic metastases than human
      adenocarcinomas. Histologic grading of ovine tumors revealed cell differentiation
      similar to that reported within human colonic adenocarcinomas. In conclusion,
      ovine intestinal adenocarcinomas, like human colonic adenocarcinomas, typically
      arise spontaneously and consistently develop widespread metastases. In addition,
      tumors appear histologically similar between these species. Therefore, sheep may
      provide a model of advanced human colonic cancer, possibly allowing evaluation of
      novel therapeutics and surgical procedures.

PMID- 16639982
TI  - Immunohistochemical distribution of tubulin beta II in human normal and
      neoplastic tissues.
AB  - Tubulin is the major constituent protein of microtubules. In mammals, there are
      seven beta-tubulins and six alpha-tubulins. Each beta-tubulin isotype has a
      unique tissue distribution. The purpose of this study was to describe the
      distribution of tubulin beta II in normal and neoplastic human tissues with
      immunohistochemical techniques. We obtained normal tissues from 33 cases (8
      fetuses, 17 neonates, 3 children and 5 adults) and 121 samples of neoplastic
      tissue from surgical specimens or at autopsy. Immunohistochemical staining for
      tubulin beta II was performed using a monoclonal antibody, KNY379 developed in
      our laboratory. Tubulin beta II was detected in various normal tissues,
      particularly in fetal and neonatal tissues, such as the nervous system, pulmonary
      alveoli, bronchioles and bronchi, colon, pancreatic ducts and acini, renal
      convoluted tubuli, skin epidermis, body cavity mesothelial cells, smooth muscle
      and thymus. In the adult, broad expression was also observed; however, the
      immunoreactivity was weaker and the extent of its distribution decreased with
      age. In neoplastic tissues, tubulin beta II immunoreactivity was detected in
      various nervous system neoplasms and other neoplasms such as pancreatic solid
      cystic carcinoma, pleomorphic adenoma, Warthin's tumor, nephroblastoma, basal
      cell carcinoma and malignant mesothelioma. We conclude that our monoclonal
      antibody, KNY379, may be useful as a marker of nervous system neoplasm,
      pancreatic solid cystic carcinoma, pleomorphic adenoma, Warthin's tumor,
      nephroblastoma, basal cell carcinoma and malignant mesothelioma.

PMID- 16639983
TI  - Cartilage change after arthroscopic repair for an isolated meniscal tear.
AB  - To investigate the direct effect to the cartilage caused by the meniscal repair,
      we examined patients who underwent an isolated meniscal repair without any other
      abnormalities by arthroscopic examination. A total of 17 patients were examined
      by second-look arthroscopy after an average interval of 9 months from the
      meniscal repair, and have been evaluated the status of the repaired meniscus and
      of the relative femoral condylar cartilage. Changes in the severity of the
      cartilage lesion between at the time of meniscal repair and the time of the
      second-look arthroscopy were considered based on the status of the repaired
      meniscus. Regardless of the healing status of the repair site, it was possible to
      prevent degeneration in the cartilage in 9 of the 10 patients who demonstrated no
      degeneration in the meniscal body. Of the 7 patients who demonstrated
      degeneration in the meniscal body, progression in cartilage degeneration was
      noted as 1 grade in 2 patients and 2 grades in another 3 patients. Even in those
      in which stable fusion of the repair site was achieved, the condition of the
      inner meniscal body was not necessarily maintained favorably in all cases,
      indicating that degeneration in the meniscal body was a risk factor for cartilage
      degeneration. It was concluded that recovery could not be expected even at 9
      months after the repair if the lesion had already demonstrated degeneration in
      the meniscal body at the time of repair.

PMID- 16639984
TI  - Pathological study on multicentric occurrence of hepatocellular carcinoma.
AB  - Recently, it has been suggested that many of hepatocellular carcinoma (HCC) are
      of multicentric origin based on the clinicopathologic studies on small HCCs of
      the early stage and clinical follow-up studies after successful treatments of
      small HCCs. The author studied the multicentric occurrence of HCC from the point
      of view of pathomorphology in 168 HCCs less than 3 cm in diameter consecutively
      resected from 1999 to 2004 and 8 autopsy of liver cirrhosis of micronodular type
      from 1990 to 2004 at Kurume University Hospital from 1999 to 2004. The
      association of well-differentiated HCC ranging from 9 mm to 1.2 cm in diameter
      was found in the non-cancerous tissue of 9 cases (9.5%) among 94 cirrhotic
      livers. Adenomatous hyperplasia (AH) was found in 7 cases (7.4%). Accordingly,
      prevalence of synchronous and metachronous multicentric hepatocarcinogenesis was
      highly suggested in 9.5% and 7.4%, respectively. In 4 (50%) of the 8 autopsy
      cases of micronodular cirrhosis, however, the coexistence of 2 well
      differentiated HCCs around 1.5 cm were found in the different segment. The
      prevalence of multicentric occurrence in the resected cases is the lowest
      estimation and true prevalence should be much more higher because HCC cases with
      multiple nodules are not sent to surgery and the observation is limited in a
      small area of the subsegmentectomized liver. Indeed, the result of autopsy cases
      reflects a true prevalence (50%) of synchronous occurrence of HCC.

PMID- 16639985
TI  - Musculoskeletal disorders among Chinese medical students.
AB  - We investigated the prevalence and distribution of Musculoskeletal Disorders
      (MSD) among Chinese medical students, by means of a questionnaire survey. A total
      of 207 questionnaires were successfully returned, giving a high response rate of
      92.4%. The MSD period-prevalence at any body site was 67.6% in the previous year
      and 46.9% in the previous week. Almost one-third of them (31.9%), reported an
      ongoing MSD. By individual body site, the most commonly affected region was the
      lower back (40.1% in the last year), followed by the neck (33.8%) and shoulders
      (21.7%). The 7 day period-prevalence also followed a similar descending pattern,
      being reported by 20.8% at the lower back and 12.1% at both the neck and knees.
      MSD affected the daily life of students for an average period of 53.8 days, with
      an average of 6.6 sick days taken from school. Students reporting high mental
      pressure were 2.9 times more likely to suffer low back pain in the previous 12
      months (OR 2.9, 95%CI 1.4-5.9, P=0.0030). Overall, our study suggests that
      Chinese medical students are at reasonable MSD risk, although it is probably
      lower than for working physicians. Further investigations are now recommended to
      elucidate the MSD mechanisms and contributory factors among medical students in
      China, as elsewhere. A longitudinal study of MSD among a complete group of
      medical students would be very useful in this regard.

PMID- 16639986
TI  - Tobacco smoking prevalence among a cross-section of dentists in Queensland,
      Australia.
AB  - The purpose of this study was to investigate the epidemiology of tobacco smoking
      among dentists in Queensland, Australia. We utilized an anonymous, self-reporting
      questionnaire which was posted to 400 dentists during 2004. The overall response
      rate was 72.1%, among whom the prevalence of current smoking was estimated to be
      3.9% (95%CI: 2.2-6.9), with a further 11.0% being ex-smokers (95%CI: 7.9-15.2).
      Smoking rates varied by age, with 6.1% of dentists aged younger than 30 years who
      were smokers. The lowest smoking prevalence was seen among dentists aged between
      30 and 40 years (1.4%), and the highest among those aged over 60 years (7.1%).
      Regarding weekly work hours, the highest smoking prevalence was seen among
      dentists who worked between 25 and 35 hrs per week (6.8%). Ex-smokers were more
      likely to work less than 25 hrs per week (21.7%). Smoking rates also varied by
      career length, with the lowest prevalence among dentists who had worked 10 to 20
      years (1.3%) and the highest rate among those who had worked over 40 years
      (6.7%). A similar trend was revealed for ex-smokers, with prevalence rates of
      1.7% and 33.3%, respectively. Overall, our study suggests that the prevalence of
      smoking is rather low among Queensland dentists. As the distribution of smoking
      was not uniform however, future preventive measures will need to consider the
      individual situation of dentists who smoke, particularly those in the older age
      groups.

PMID- 16639987
TI  - Induction of neuronal tolerance by electroconvulsive shock in rats subjected to
      forebrain ischemia.
AB  - We have examined ischemic tolerance induced by electroconvulsive shock before
      exposure to forebrain ischemia. Subjects were 40 rats, which were randomly
      allocated to control, single ECS (sECS), repeated ECS (rECS) or sham group. sECS
      group and rECS group received ECS only once 2 days before the subsequent 8-min
      forebrain ischemia and once a day for 9 consecutive days until 2 days before the
      exposure to ischemia, respectively. Forebrain ischemia was produced by modified
      bilateral carotid artery occlusion technique. Control group underwent brain
      ischemia without ECS pretreatment. Sham group received ECS without following
      exposure to ischemia. Pyramidal cell injury of the hippocampal CA1 sector was
      microscopically examined on the 7th day after the ischemic exposure or the sham
      operation. Damage of the pyramidal cells was assessed by the injury ratio, which
      was ratio of non-viable pyramidal cells to the whole pyramidal cells. The injury
      ratios of CA1 pyramidal cells in sECS, rECS and control groups were 30.5 +/- 10.8
      (n=10), 42.3 +/- 18.4% (n=10) and 90.4 +/- 2.9% (n=9), respectively. The injury
      ratios in sECS and rECS groups were lower than the ratio in control group
      (p<0.01), while the ratios of sECS and rECS groups were not different. The
      pyramidal cells in sham group were intact. Our results indicate that both
      preconditionings of sECS and rECS have a potency to induce delayed tolerance
      against temporary forebrain ischemia, though the potency was not different
      between sECS and rECS. Electroconvulsive shock may be added to the list of
      preconditioning stimuli to protect brain against ischemic neuronal damage.

PMID- 16639988
TI  - A case of mediastinal pancreatic pseudocyst successfully treated with
      somatostatin analogue.
AB  - A 57-year-old man with a 3-year history of chronic pancreatitis was admitted to
      our hospital with upper abdominal pain. Based on examination findings, the
      patient was diagnosed as having pseudocysts in the pancreatic body and the
      mediastinum that were associated with acute aggravation of chronic pancreatitis.
      Because of the patient refused an operation, he was submitted to conservative
      management including intramuscular injection with somatostatin analogue of 100
      microg/day. On the 14th day of the treatment, pleural effusion and pseudocyst in
      the pancreatic head were additionally diagnosed based on the findings of computed
      tomography, magnetic resonance imaging and other examinations, and the dose of
      somatostatin analogue was increased to 200 microg/day. As a result, on the 28th
      day of the treatment, pancreatitis was inactivated, and the pseudocysts in the
      mediastinum and the pancreas disappeared. The patient has been followed up for 15
      months, and there has been no recurrence.

PMID- 16639989
TI  - Evidence-based medicine in pathology: an introduction.
AB  - Evidence-based medicine (EBM) is a school of thought that has spread rapidly
      through medicine in the past 2 decades and is eliciting an increasing interest in
      Anatomic Pathology and Laboratory Medicine. It has been defined as "the
      conscientious, explicit, and judicious use of current best evidence in making
      decisions about the care of individual patients." The environmental factors that
      created a need for EBM and basic concepts of this discipline are reviewed.
      Methods for the accrual and critical appraisal of the validity of available
      evidence and its impact, applicability and usefulness in pathology practice are
      discussed. Basic concepts of bayesian data analysis with an emphasis on concepts
      such as prior and posterior probability and the use of "holdout" or "test" data
      are introduced. The future of EBM in pathology is discussed and potential
      applications of these concepts to pathology practice and research are proposed.

PMID- 16639990
TI  - Evidence-based principles and practices in pathology: selected problem areas.
AB  - Contrary to the intuitive impression of most pathologists, there are still many
      areas in laboratory medicine where evidence-based medicine (EBM) principles are
      not applied. These include aspects of both anatomic and clinical pathology. Some
      non-EBM practices are perpetuated by clinical "consumers" of laboratory services,
      because of inadequate education, habit, or over-reliance on empirical factors.
      Other faulty procedures are pathologist-driven, with similar underpinnings. This
      overview considers several exemplary problem areas representing non-EBM practices
      in the hospital laboratory. Such examples include ideas and techniques centering
      on metastatic malignancies, "targeted" oncological therapy, analysis of surgical
      margins in the excision of neoplasms, general laboratory testing and data
      utilization, evaluation of selected coagulation defects, administration of blood
      products, and analysis of hepatic iron-overload syndromes. The concepts
      illustrating departures from EBM are discussed for each of those topics.

PMID- 16639991
TI  - An observational examination of the literature in diagnostic anatomic pathology.
AB  - Original research published in the medical literature confronts the reader with
      three very basic and closely linked questions--are the authors' conclusions true
      in the contextual setting in which the work was performed (internally valid); if
      so, are the conclusions also applicable in other practice settings (externally
      valid); and, if the conclusions of the study are bona fide, do they represent an
      important contribution to medical practice or are they true-but-insignificant?
      Most publications attempt to convince readers that the researchers' conclusions
      are both internally valid and important, and occasionally papers also directly
      address external validity. Developing standardized methods to facilitate the
      prospective determination of research importance would be useful to both journals
      and their readers, but has proven difficult. In contrast, the evidence-based
      medicine (EBM) movement has had more success with understanding and codifying
      factors thought to promote research validity. Of the many variables that can
      influence research validity, research design is the one that has received the
      most attention. The present paper reviews the contributions of EBM to
      understanding research validity, looking for areas where EBM's body of knowledge
      is applicable to the anatomic pathology (AP) literature. As part of this project,
      the authors performed a pilot observational analysis of a representative sample
      of the current pertinent literature on diagnostic tissue pathology. The results
      of that review showed that most of the latter publications employ one of the four
      categories of "observational" research design that have been delineated by the
      EBM movement, and that the most common of these observational designs is a "cross
      sectional" comparison. Pathologists do not presently use the "experimental"
      research designs so admired by advocates of EBM. Slightly > 50% of AP
      observational studies employed statistical evaluations to support their final
      conclusions. Comparison of the current AP literature with a selected group of
      papers published in 1977 shows a discernible change over that period that has
      affected not just technological procedures, but also research design and use of
      statistics. Although we feel that advocates of EBM deserve credit for bringing
      attention to the close link between research design and research validity, much
      of the EBM effort has centered on refining "experimental" methodology, and the
      complexities of observational research have often been treated in an
      inappropriately dismissive manner. For advocates of EBM, an observational study
      is what you are relegated to as a second choice when you are unable to do an
      experimental study. The latter viewpoint may be true for evaluating new
      chemotherapeutic agents, but is unacceptable to pathologists, whose research
      advances are currently completely dependent on well-conducted observational
      research. Rather than succumb to randomization envy and accept EBM's assertion
      that observational research is second best, the challenge to AP is to develop and
      adhere to standards for observational research that will allow our patients to
      benefit from the full potential of this time tested approach to developing valid
      insights into disease.

PMID- 16639992
TI  - Classification of error in anatomic pathology: a proposal for an evidence-based
      standard.
AB  - Error in anatomic pathology (EAP) is an appropriate problem to consider using the
      disease model with which all pathologists are familiar. In analogy to medical
      diseases, diagnostic errors represent a complex constellation of often-baffling
      deviations from the "normal" condition. Ideally, one would wish to approach such
      "diseases of diagnosis" with effective treatments or preventative measures, but
      interventions in the absence of a clear understanding of pathogenesis are often
      ineffective or even harmful. Medical therapy has its history of "bleeding and
      purging," and error-prevention has a history of "blaming and shaming." The urge
      to take action in dealing with either medical illnesses or diagnostic failings
      is, of course, admirable. However, the principle of primum non nocere should
      guide one's action in both circumstances. The first step in using the disease
      model to address EAP is the development of a valid taxonomy to allow for grouping
      together of abnormalities that have a similar pathogenesis. It is apparent that
      disease categories such as "tumor" are not valuable until they are further
      refined by precise and accurate classification. Likewise, "error" is an
      impossibly broad concept that must be parsed into meaningful subcategories before
      it can be understood with sufficient clarity to be prevented. One important EAP
      subtype that has been particularly difficult to understand and classify is
      knowledge-based interpretative (KBI) error. Not only is the latter sometimes
      confused with distinctly different error types such as human lapses, but there is
      danger of mistaking system-wide problems (eg, imprecise or inaccurate diagnostic
      criteria) for the KBI errors of individual pathologists. This paper presents a
      theoretically-sound taxonomic system for classification of error that can be used
      for evidence-based categorization of individual cases. Any taxonomy of error in
      medicine must distinguish between the various factors that may produce mistakes,
      and importantly, whether they are individual, small system (e.g., my histology
      laboratory), or big system (e.g., published diagnostic criteria). Because no
      overarching governing agency exists to coordinate this initiative, the
      recognition of need and effective implementation of EAP counter-measures must
      emanate from our specialty group itself.

PMID- 16639993
TI  - Diagnostic precision and accuracy in interpretation of specimens from cancer
      screening programs.
AB  - Few areas in modern medicine provide a better example of evidence-based data than
      the anatomic pathologists' classification of fully developed malignancies.
      Beginning with the Papanicolaou (Pap) smear, morphologic tools also were applied
      to specimens obtained in cancer screening programs directed at large,
      asymptomatic patient populations. The Papanicolaou test was quickly responsible
      for a reduction in the incidence of invasive squamous cell carcinoma of the
      cervix, proving the concept that screening could interdict the development of
      advanced malignancy. Other screening programs followed the Papanicolaou test
      initiative, producing a revolutionary change in the specimens submitted to
      pathologists. Cancer screening generates specimens containing morphologic
      deviations from normal that are thought to put currently healthy patients at risk
      of future malignancy. However, translating morphologic findings in such samples
      into risk estimates raises a number of statistical and ethical problems. When
      diagnostic thresholds are set to favor specificity, unwanted false-negative
      results accrue. Conversely, aiming at sensitivity over specificity is associated
      with biologically false-positive results, which are likewise undesirable.
      Pathologists interpreting these specimens find themselves facing a screening
      paradox. These screening programs attempt to discover the very earliest changes
      of neoplastic transformation, but these same earliest changes are inherently the
      most difficult to identify with precision and accuracy. This paper discusses
      these challenges.

PMID- 16639994
TI  - The application of special technologies in diagnostic anatomic pathology: is it
      consistent with the principles of evidence-based medicine?
AB  - Proponents of evidence-based medicine (EBM) have emphasized the need to consider
      the quality of different sources of medical information and have proposed various
      methods to integrate available "best evidence" into rules, guidelines and other
      diagnostic, therapeutic and prognostic models. The various factors that can
      affect the internal validity of studies in anatomic pathology, such as
      interobserver variability, use of retrospective rather than prospective data and
      others, are reviewed. The need for testing for the external validity of the
      results of anatomic pathology studies is introduced, using "test sets" of cases
      that have not been used to generate the classification or prognostic models. This
      methodology has been seldom used in anatomic pathology to validate the
      generalizability of various "entities," usefulness of diagnostic tests under
      different conditions and other information. Basic concepts of meta-analysis for
      research synthesis are introduced; these methods have been seldom used in
      anatomic pathology to integrate information from different studies using
      quantitative techniques rather than summary tables that merely list the results
      of various publications. The potential use of decision analysis and value of
      information analysis for the adoption of new tests is briefly discussed.

PMID- 16639995
TI  - Evidence-based medicine and tort law.
AB  - Recent statutes and legal decisions have been aimed at bettering the quality of
      tort-law decisions by substantively improving "expert" testimony. However, in
      analogy to the experience of physicians attempting to upgrade medical practice
      using the principles of evidence-based medicine, lawyers and the courts have
      found it much easier to describe ideal science than to actualize it. This is
      particularly so in a system (the Law) that has traditionally not been very
      discerning about scientific rigor, and which has established procedural
      priorities that are often incompatible with strict scientific standards. This
      overview will examine the American tort system from an evidence-based
      perspective. We include a discussion of standards that could be used for
      "outcomes analysis" in the Law; recognition and classification of errors made by
      the courts themselves; the relationship between medical errors, "negligence," and
      standard of care; and the problem of reconciling the rights of plaintiffs with
      medical-scientific facts. We also consider selected impediments to developing a
      legal system that is capable of consistently reaching evidence-based decisions
      concerning complex scientific information, including pathologic interpretation of
      tissue specimens.

PMID- 16639996
TI  - Variability of practice in anatomic pathology and its effect on patient outcomes.
AB  - Variability in the delivery of medical care negatively affects patient outcomes
      and contributes to escalating health care costs. Such heterogeneity exists on
      geographic, provider-related, institutional, and financial levels. Efforts to
      reduce it have resulted in the development of evidence-based clinical practice
      guidelines that have been only inconsistently adopted. Testing patterns in
      anatomic pathology (AP) also manifest considerable inconsistency, further
      contributing to suboptimal health outcomes and increased costs. Test variability
      in AP can be identified in its clinician-dependent preanalytic aspect and in the
      analytic phase as well, including the gross prosection of specimens, their
      processing, and reporting formats. To address selected facets of these issues,
      pathologists have developed practice guidelines that generally are based on
      "expert" opinion, representing the weakest form of evidence. Interpretative
      variability in AP has been investigated in numerous published studies that have
      measuring the "kappa statistic." Few of those analyses have addressed the impact
      of diagnostic disagreement on patient care; in addition, proposed and effective
      methods to reduce interpretative variability have only rarely been included.

PMID- 16639997
TI  - It is time to call for perinatal prevention of allergy diseases.

PMID- 16639998
TI  - The long-term outcome of children with isolated congenital complete
      atrioventricular block.
AB  - Patients with isolated congenital complete atrioventricular block (CCAVB) may
      revert to a lower degree of atrioventricular block and do not require pacemaker
      treatment. The change of rhythm is less well studied in pediatric patients. The
      aim of this study was to report the long-term outcome of pediatric patients with
      isolated CCAVB at our institution, with emphasis on restoration of sinus rhythm.
      We reviewed the medical records of 16 consecutive children with isolated CCAVB at
      our institution. They were divided into a prenatal group (n=9) and a postnatal
      group (n=7). In the prenatal group, with follow-up of 28 months (median, range 1
      154 months), one patient without symptoms had transient restoration of sinus
      rhythm and did not require pacemaker therapy, five patients required pacemaker
      therapy and three of them died, and the remaining three patients without symptoms
      did not require pacemaker therapy. In the postnatal group, with follow-up of 84
      months (median, range 14-133 months), one patient without symptoms had
      restoration of sinus rhythm and did not require pacemaker therapy, three patients
      required pacemaker therapy and survived, and the remaining three patients without
      symptoms did not require pacemaker therapy. Compared to the postnatal group, the
      prenatal group needed earlier pacing and had higher rate of maternal
      autoantibodies. There were no significant differences in sex, pacemaker
      implantation rate, dilated cardiomyopathy, and mortality rate between the two
      groups. Pacemaker implantation is indicated in most patients with isolated CCAVB,
      but a change to a lower degree of block can occur in some pediatric patients who
      may not require pacemaker implantation.

PMID- 16639999
TI  - Nasopharyngeal carcinoma in children: a single institution's experience.
AB  - Nasopharyngeal carcinoma is a very rare disease of children. Between 1992 and
      2005, 8 male and 2 female patients [ages ranging from 12 to 17 years,] were
      treated in our institution. The histopathologies were all undifferentiated type
      (WHO Type III). Of the ten patients, one was T2, five were T3, and four were T4,
      respectively (TNM system of the American Joint Committee for Cancer Staging).
      Eight patients had node metastases, 6/8 had bilateral and 4/8 had nodes larger
      than 6 cm. The main symptoms at diagnosis were neck mass followed by nasal, aural
      symptoms, cranial nerve palsy and headache. Four patients received radiotherapy
      only, while six patients received cisplatin-based concomitant chemoradiotherapy.
      The mean irradiation doses to the primary sites were 7200 cGy. Two patients
      developed early systemic relapse and died one year and 4 months, respectively,
      after relapse. After a median follow-up of 30 months, the event-free survival and
      overall survival were 70% and 75%, respectively. Although the sample size was
      small, it seemed that the patients had a good chance of survival in spite of
      advanced stage. However, late morbidity was a concern.

PMID- 16640000
TI  - Predictability of early onset atopic dermatitis by cord blood IgE and parental
      history.
AB  - Cord blood IgE and atopic family history have been used as predictors of atopic
      disease in infants for more than 20 years. In recent years, the value of cord
      blood IgE in predicting the development of atopic dermatitis has been questioned,
      while family history of atopy has consistently been regarded as a useful
      predictor for atopic dermatitis. A birth cohort was followed-up to 6 months of
      age to record the development of atopic dermatitis and to study its association
      with cord blood IgE levels and parental history of atopy. The cumulative
      incidence of atopic dermatitis over the 1st, 3rd and 6th months of life amounted
      to 5.0%, 8.2% and 14.0%, respectively. When the cutoff value for cord blood IgE
      was set at 0.5 kU/L, there was a significant association between elevated cord
      blood IgE level and atopic dermatitis at 1, 3 and 6 months of age; when the
      cutoff value was set at 0.9 kU/L, the association was only found at 3 months of
      age. There was a significant association with atopic history of the mother. The
      effect of maternal atopic history on atopic dermatitis seen only at 1 month was
      lost by 3 months of age. There was no correlation between paternal history and
      atopic dermatitis. In our study, the predictive capacity of maternal history and
      cord blood IgE was not high enough to recommend them as screening factors.

PMID- 16640001
TI  - Leptin changes in Taiwanese girls with central precocious puberty before and
      during the GnRH agonist treatment.
AB  - To examine the relationship between leptin serum levels and pubertal development
      in girls with progressive central precocious puberty. We longitudinally
      investigated the leptin levels of 37 girls with central precocious puberty before
      and during treatment with the gonadotropin-releasing hormone agonist depot
      (leuprorelin acetate). Leptin and other hormone levels were determined by
      radioimmunoassay. Girls with central precocious puberty before treatment showed
      no significant difference in leptin levels as compared to the puberty stage at
      diagnosis of disease. In addition, the changes in leptin concentrations of girls
      with central precocious puberty during treatment were not statistically
      significant. In the Spearman correlation analysis of leptin levels with body mass
      index, bone age, chronological age, clinical pubertal signs along with
      luteinizing, follicle-stimulating, and estradiol hormone levels, we found that
      body mass index, weight, and chronological age were significantly correlated with
      leptin levels (p < 0.05) at both 3 and 6 months of leuprorelin treatment. Leptin
      levels increased with body mass index; however, this trend did not reach
      statistical significance at all follow-up time points. These data demonstrated
      that treatment with depot gonadotropin-releasing hormone agonist does not
      influence leptin concentrations. Serum leptin levels in patients with central
      precocious puberty are associated with body weight and body mass index.

PMID- 16640002
TI  - Chlamydia trachomatis pneumonia: experience in a medical center.
AB  - Chlamydia trachomatis is one of the important causes of afebrile pneumonia in
      infants. The purpose of this study was to evaluate the demographic features,
      clinical manifestations, and outcome of C. trachomatis pneumonia patients seen
      during the past 10 years in one medical center. We reviewed the records on 30
      patients with a diagnosis of C. trachomatis pneumonia. The diagnosis was based on
      characteristic clinical features and confirmed by culture, serologic testing, or
      polymerase chain reaction (PCR). Clinical features including age, sex, symptoms
      at the time of admission, laboratory data, and treatment were analyzed. Of the 30
      patients (17 males and 13 females), 29 (96%) were less than 4 months old (range
      10 days to 5 months). All patients had productive cough followed by tachypnea.
      Three patients (10%) presented with apnea. Four (13%) had conjunctivitis. Fever
      was present in only 3 (10%), of whom 2 also had concurrent respiratory syncytial
      virus infection. Peripheral eosinophilia (eosinophils > or = 400/mm3) was present
      in 14 (47%) patients. Hyperinflation was seen on chest x-ray in 15 patients. All
      infants were treated with erythromycin and responded well. The mean time to
      clinical improvement was 3.53 days after the start of treatment. The mean
      duration of hospitalization was 8.97 days (range, 3 to 17 days). No patients
      died. Pediatricians and general practitioners must have a high index of suspicion
      for chlamydial infection in afebrile infants presenting with tachypnea,
      peripheral eosinophilia, and hyperinflation on chest x- ray during the first four
      months of life.

PMID- 16640003
TI  - Neonatal readmission within 2 weeks after birth.
AB  - To examine the causes of neonatal readmission within two weeks of discharge and
      identify the factors associated with neonatal readmission, newborns readmitted to
      Kaohsiung Municipal Hsiao-Kang (KMHK) Hospital within two weeks of discharge from
      our nursery between October 2001 and November 2003 were studied retrospectively.
      Of the 1099 deliveries during the study period, there were 63 newborns readmitted
      to KMHK Hospital within 14 days of discharge, with a rate of 5.7%. The control
      group consisted of a systematic sampling of newborns delivered over the same
      period that were not readmitted (n=74). The diagnoses of readmission included
      jaundice (73.0%), fever and suspected sepsis (19.0%), enteritis (4.8%), and
      others (3.2%). Factors associated with readmission included length of stay in
      nursery less than 72 hours, exclusive breast feeding, more body weight loss, and
      higher bilirubin level at discharge from nursery. After multiple logistic
      regression analysis, length of stay in nursery less than 72 hours, exclusive
      breast feeding and higher bilirubin level at discharge from nursery were the
      significant risk factors for neonatal readmission.

PMID- 16640004
TI  - Deep sedation with methohexital or thiamylal with midazolam for invasive
      procedures in children with acute lymphoblastic leukemia.
AB  - Pediatric oncology/hematology patients, especially those with acute lymphoblastic
      leukemia (ALL), often undergo repeated painful invasive procedures. Deep
      sedation, mandatory for these procedures in young children, can reduce patient
      anxiety and get their compliance during procedures. This study assessed clinical
      experience of employing methohexital or thiamylal with midazolam as sedative for
      elective invasive procedures in children with ALL. Between November 1997 and
      March 2004, 20 out of 33 ALL children received deep sedation after evaluation,
      mainly because of relatively young age (mean age 4.60 +/- 2.03 years). A total of
      176 procedures were done, with 139 being intrathecal therapy. There were 98 and
      78 procedures for the methohexital and thiamylal groups, respectively. The
      average dosages to complete the procedures were 2.2 +/- 1.2 mg/kg for
      methohexital and 3.4 +/- 2.1 mg/kg for thiamylal. One out of the 176 procedures
      was failed due to bradycardia, hypotension and cyanosis, in the methohexital
      group. Otherwise, no significant adverse events were found. Increased heart rate
      (HR) during stable blood pressure (BP) was observed in both groups. In
      conclusion, under careful monitoring and performed by experienced practitioners,
      the application of methohexital or thiamylal combined with midazolam to achieve
      deep sedation for invasive procedures in young children with ALL is safe.

PMID- 16640005
TI  - Disseminated pneumococcal infection with pericarditis and cardiac tamponade:
      report of one case.
AB  - A 1-year-5-months-old female who had cough, rhinorrhea and prolonged fever for 19
      days was admitted to the intensive care unit due to exertional dyspnea. She was
      intubated promptly in virtue of hypotension and cyanosis. The physical
      examination demonstrated diminished breathing sound over the right lung and
      distant heart sound; echocardiogram showed cardiac tamponade. Further X ray study
      showed right hydropneumothorax and cardiomegaly. Pericardiocentesis and chest
      thoracostomy were performed, and subsequently all the cultures showed growth of
      Streptococcus pneumoniae. Antibiotics therapy was started promptly after
      admission. Further investigation indicated osteomyelitis of the right ilium, so
      that surgical debridement was done. The patient was discharged 54 days later with
      complete recovery. After following up for 18 months, no restrictive heart disease
      developed. Purulent pericarditis with cardiac tamponade is an extremely rare
      complication of pneumococcal infection.

PMID- 16640006
TI  - Severe anemia in a newborn due to massive fetomaternal hemorrhage: report of one
      case.
AB  - We report a case of a newborn with unexpected severe anemia. A woman, at 38 5/7
      weeks of gestational age, presented with decreased fetal movement. A sinusoidal
      fetal heartbeat waveform and late deceleration pattern on fetal monitoring
      strengthened the decision for emergent Cesarean section. Using the frequency of
      fetal movement and the fetal heart monitoring pattern, together with detecting
      fetal hemoglobin in maternal blood circulation by the Kleihauer-Betke test and
      hemoglobin electrophoresis, fetomaternal hemorrhage can be detected earlier and
      provide for better fetal outcomes.

PMID- 16640007
TI  - Primary intraspinal mesenchymal chondrosarcoma: report of one case.
AB  - We report a case of primary intraspinal mesenchymal chondrosarcoma in an 11-year
      old boy. Contrast-enhanced MRI revealed a hyperintense, sausage-shaped mass
      extending from C7 to T2. The lesion located anterolaterally on the left side,
      pushing the spinal cord to the right and posterior. Microscopic examination and
      immunohistochemical studies confirmed the diagnosis of mesenchymal
      chondrosarcoma. Follow-up studies have shown no tumor recurrence for 2 years.
      This tumor is rare but should be considered for differential diagnosis in spinal
      tumors.

PMID- 16640008
TI  - Ring-sling complex: report of one case.
AB  - The ring-sling complex is a rare developmental anomaly combining pulmonary artery
      sling and complete tracheal ring. The abnormal left pulmonary artery is a sling
      like structure that surrounds the trachea and produces upper airway obstruction.
      Complete tracheal ring is associated with tracheal stenosis which often leads to
      respiratory distress. This article presents a case of this anomaly and emphasizes
      the importance of detecting the complex combination when evaluating related
      disease spectrum.

PMID- 16640009
TI  - Freeman-Sheldon syndrome: report of one case.
AB  - Freeman-Sheldon syndrome is a rare disorder, and the diagnosis is clinical by
      unusual facial features and skeletal abnormalities. It was first described by
      Freeman and Sheldon in 1938; since then, cases of Freeman-Sheldon syndrome have
      been reviewed extensively. There is genetic heterogeneity, but most cases are
      thought to be sporadic. Aspiration pneumonia and respiratory difficulties are the
      main causes of early mortality. In Taiwan, only a few cases have been reported
      before. We report here one full-term male newborn with normal prenatal
      examination that was diagnosed as Freeman-Sheldon syndrome by typical
      characteristics after birth. The brain magnetic resonance imaging showed normal
      development. The patient also combined with blepharosynechia, congenital heart
      disease and abnormal electroencephalography, which are rare in Freeman-Sheldon
      syndrome. He was treated for mild respiratory difficulties and feeding problem at
      hospital in the first month of his life and discharged without obvious eventful
      condition, except still on nasogastric tube feeding. Unfortunately, the patient
      expired at home at the age of 2 months, but the parents refused autopsy.

PMID- 16640010
TI  - Eikenella corrodens arthritis of the knee after a toothpick injury: report of one
      case.
AB  - This is a case of an 11-year-old boy who developed septic arthritis of the right
      knee after a stabbing injury by a toothpick. Arthroscopic debridement of the
      distal femur and arthrotomy with synovectomy were performed at two hospitals.
      Cultures from both yielded Eikenella corrodens, an organism that may be normally
      found in oral secretions. The boy was given treatment with intravenous
      ceftriaxone after surgery and discharged home without complications. E. corrodens
      is part of the normal human oropharyngeal flora. It has been reported as the
      cause of infections at many sites, which are largely due to contamination with
      oral secretions. A penetrating injury with an object contaminated with oral
      bacterial flora should lead clinicians to consider this organism as a potential
      pathogen.

PMID- 16640011
TI  - Congenital coxsackievirus B5 infection: report of one case.
AB  - In infants and children, enterovirus (EV) infections are very common. In
      neonates, EV infections may lead to fatal myocarditis, encephalitis, or
      necrotizing hepatitis. Transplacental viremia before delivery is possible but has
      only been demonstrated occasionally. The presence or absence of passively
      acquired maternal antibody specific for the infecting EV serotype plays the most
      important role in neonatal EV infections. We report a fatal case of congenital
      coxsackievirus B5 infection, confirmed by culture of the virus from the patient's
      throat and rectal swab and from his mother's throat. The mother had suffered from
      fever for 1 week since 9 days before delivery. Fever subsided 2 days before the
      day of delivery, but absence of fetal movements was noted. The newborn's 4-year
      old elder sister also had suffered from fever with upper respiratory symptoms
      during the same period. Fever occurred in this baby immediately after birth by
      cesarean section, suggesting the presence of transplacental virus transmission.

PMID- 16640012
TI  - Protest nursing issues when speaking out as a nurse.

PMID- 16640013
TI  - Reader's personal experience shows the ugly side of healthcare.

PMID- 16640014
TI  - Thanks for getting the word out on post-polio syndrome.

PMID- 16640015
TI  - How would you like your employer to recognize you and your colleagues during
      nurses week?

PMID- 16640016
TI  - Drawing blood for ABGs.

PMID- 16640017
TI  - Urine test boosts detection of recurrent bladder cancer.

PMID- 16640018
TI  - Drug watch '06. Pain relievers.

PMID- 16640019
TI  - The teaching power of high-tech dummies.

PMID- 16640020
TI  - Bioterrorism! We put our plan to the test.

PMID- 16640021
TI  - Help stamp out this lingering menace.

PMID- 16640022
TI  - Ready, set...go!

PMID- 16640023
TI  - As free as the birds.

PMID- 16640024
TI  - How about a law degree?

PMID- 16640025
TI  - The fate of iron in the organism and its regulatory pathways.
AB  - Iron is an essential element involved in many life-necessary processes.
      Interestingly, in mammals there is no active excretion mechanism for iron.
      Therefore iron kinetics has to be meticulously regulated. The most important step
      for regulation of iron kinetics is absorption. The absorption takes place in
      small intestine and it is implicated that it requires several proteins. Iron is
      then released from enterocytes into the circulation and delivered to the cells.
      Iron movement inside the cell is only partially elucidated and its traffic to
      mitochondia is not known. Surprisingly, the regulation of various proteins
      related to iron kinetics and energy metabolism at the molecular level is better
      described. On contrary, the complex control of iron absorption cannot be fully
      explicated with present knowledge.

PMID- 16640026
TI  - Expression of cytoskeletal proteins in hepatic stellate cells isolated from
      normal and cirrhotic rat liver.
AB  - Hepatic stellate cells (HSC) are located in Disse spaces of normal rat liver. In
      their quiescent state they serve as a storage site for vitamin A. In fibrotic
      liver they become activated, proliferate and they undergo transdifferentiation
      into myofibroblast-like cells. Changes in the cell phenotype are accompanied by
      changes in the cellular cytoskeleton. We have studied the expression of alpha
      smooth muscle actin and intermediate filament proteins vimentin, desmin and glial
      fibrillary acidic protein (GFAP) by immunocytochemistry in HSC cultured for 2 or
      7 days after isolation. Normal or cirrhotic rat liver was perfused with solutions
      of pronase and collagenase and HSC were isolated by density gradient
      centrifugation of the resulting cell suspension. Liver cirrhosis was produced in
      rats by repeated carbon tetrachloride administration. Vimentin was detected in
      all cells from normal and cirrhotic liver. The concentration of desmin in the
      cells from cirrhotic liver was slightly higher than that in normal cells and it
      increased with time in culture. GFAP could be detected only in normal cells 2
      days after their isolation. In contrast, alpha smooth muscle actin (alpha-SMA)
      was absent from normal cells at this time but its expression was pronouced later.
      In most cells from cirrhotic liver this antigen was already present on the second
      day of culture and its expression further increased.

PMID- 16640027
TI  - In vitro inactivation of rat brain acetylcholinesterase by DSP-4 and its
      derivatives OS-21 and OS-23 and protective activity of tacrine (9-amino-1,2,3,4
      tetrahydroacridine).
AB  - Tertiary N-haloethylamines are able to cyclize to the corresponding aziridinium
      ions. The inhibitory activity of the DSP-4 (N-(o-brombenzyl)-N-ethyl-2
      chlorethylamine) and its two derivatives OS-21 (N-benzyl-N-ethyl-2
      chloroethylamine) and OS-23 (N-fenylethyl-N-ethyl-2-chloroethylamine) was studied
      toward rat brain acetylcholinesterase (AChE) in vitro. The influence of the THA
      (tacrine; 9-amino-1,2,3,4-tetrahydroacridine) on AChE inhibition by these
      substances was also evaluated. The results demonstrated that all of three
      aziridinium compounds formed in solution caused a time- and concentration
      dependent irreversible enzyme inhibition. The association of aziridinium
      compounds with the AChE was a relatively slow second-order reaction. DSP-4 showed
      the fastest rate of AChE alkylation, OS-21 had a lowered rate and OS-23 displayed
      the lowest rate. Pretreatment of the enzyme by THA decreased the rate of
      alkylation by all three aziridinium compounds by allosteric mechanism.

PMID- 16640028
TI  - Comparison of the effects on spinal reflexes of acetylsalicylate and metamizol in
      spinalized and normal rats.
AB  - The effects of nonsteroidal antiinflammatory drugs, acetylsalicylate and
      metamizol, on spinal monosynaptic reflexes were investigated in spinalized and
      normal rats. Adult rats (n=36) weighing 150-200 g were anesthetized with ketamine
      and artificially ventilated. Half of rats were spinalized at C1 level. A
      laminectomy was performed in the lumbosacral region. Following electrical
      stimulation of the sciatic nerve by single pulses, reflex potentials were
      recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered
      orally (100 mg/kg for both spinalized and normal rats). Metamizol was
      administered intramuscularly (15 mg/kg for both spinalized and normal rats).
      These drug administrations significantly decreased the amplitude of reflex
      response in all groups (p < 0.05). These data verify that observed inhibition by
      acetylsalicylicate and metamizol may be at the level of spinal cord. Also we
      suggested that the cyclooxygenase products of arachidonic acid may play an
      important role in regulating the reflex potential.

PMID- 16640029
TI  - Transplantation of bone marrow derived progenitor cells in acute myocardial
      infarction. The first results.
AB  - The intracoronary administration of autologous bone marrow cells (BMCs) has been
      shown to improve the left ventricle function in the course of acute myocardial
      infarction. Therefore we have started a clinical trial using transplantation of
      BMCs in the acute phase of myocardial infarction. The aim of our study is to
      assess the feasibility and safety of this procedure, and effect on the left
      ventricle function of these patients. We describe the first experience in two
      patients with acute myocardial infarction reperfused using direct stenting. The
      aspiration of bone marrow from the sternum provided sufficient amount of the
      cells for transplantation. No serious ischemia and no changes in coronary artery
      patency were detected after intracoronary infusion. The left ventricle ejection
      fraction was increasing throughout the time of three-month follow-up. No other
      complications (ventricular arrhythmias, reinfarction, thrombus formation) were
      detected.

PMID- 16640030
TI  - Magnesium urinary excretion in diabetic adolescents.
AB  - OBJECTIVE: To define peculiarities of urinary magnesium (Mg) excretion in
      diabetic adolecents; to elucidate gender-related differences in Mg urinary
      excretion; to determine urinary Mg excretion differences between diabetic and age
      matched healthy children. The diurnal, nocturnal and 24-h urinary Mg level in
      adolescent boys and girls (aged 13-17 years) with type I diabetes mellitus (DM)
      and in age-matched control groups of healthy boys and girls was examined.
      Additionally the adolescent girls were examined during different phases of their
      menstrual cycle. RESULTS: Diurnal, overnight and 24-h Mg urinary excretion in
      diabetic adolescent boys and girls was significantly higher than in healthy ones.
      In diabetic boys 24 h Mg excretion was higher than in diabetic girls (4.59 +/-
      1.4 vs. 3.34 +/- 1.5 mmol; p < 0.05). The investigation showed gender-related
      differences in Mg urinary excretion in healthy adolescents: 24-h Mg urinary
      excretion was significantly higher in boys than in girls (2.66 +/- 0.9 vs. 2.1 +/
      0.9 mmol; p < 0.05). The level of Mg in the nocturnal urine of boys and girls
      was significantly higher than in diurnal. Urine Mg was negatively related to
      height in adolescent girls. CONCLUSION: Diabetic adolescents excrete
      significantly more Mg with urine as compared to healthy ones.

PMID- 16640031
TI  - Mucosal mast cells in irritable bowel syndrome and inflammatory bowel disease.
AB  - Even though exciting progresses have been until now, further studies are
      necessary to clearly understand the significance of MMC. Mast cells are thought
      to participate in the pathogenesis of inflammatory bowel disease and irritable
      bowel syndrome. However, their role in the pathogenesis remains unsettled. The
      specific aims of this study were to (1) examine mucosal mast cell counts in the
      cecum in patient with IBS, and IBD (2) compare MMC between the disease groups. We
      showed increased MMC count in IBS.

PMID- 16640032
TI  - The changes of peripheral nerve microstructure after surgical manipulation-
      experiment on rat model.
AB  - The aim of our study was to describe histopathology of the peripheral nerve after
      its circular release followed by embedding in different environs. We operated on
      18 male rats divided into 3 groups. In the first group right femoral nerve was
      surgically released. In the second group the nerve was enveloped by the
      subcutaneous fat flap. In the third one the nerve was wrapped up by the skeletal
      muscle. Six weeks later the animals were killed by exsanguination. The femoral
      nerve, in the first group, did not show any pathological changes. In the second
      group 3 animals appeared normal or nearly normal, nevertheless in 3 of them
      perineural fibrosis and axonal degeneration were observed. Histological reaction
      in the third group disclosed dispersed axonal injury. Our experiments using rat
      model imitate situation in humans. The results obtained will help us in making
      meaningful decision when performing peripheral nerve injury.

PMID- 16640033
TI  - Two siblings with fulminant viral hepatitis A: case report.
AB  - Fulminant hepatitis is a rare complication of acute hepatitis A infection.
      Nevertheless, the seroepidemiology of the infection is rapidly changing with the
      developing world, rendering more adults susceptible to the infection, in
      particular with more severe course. We report here fulminant hepatitis A
      infection with a mortal course during an epidemic period in two siblings.
      Although it causes a self-limited mild disease, hepatitis A virus may have a
      severe course including fulminant hepatitis and may lead to mortality, especially
      in older ages. Hence, the risk of hepatitis A virus infection and its
      complications should be reduced with measures of immunization and sanitation.

PMID- 16640034
TI  - Echocardiographic evaluation for Kawasaki disease--a powerful tool for diagnosis
      and follow-up?!

PMID- 16640035
TI  - No association between TAP1 DpnII polymorphism and bronchopulmonary dysplasia.
AB  - The possibility that a family history of asthma may have a role in susceptibility
      to bronchopulmonary dysplasia (BPD) had been raised in several reports, and there
      was evidence of a strong association between transporter associated with antigen
      processing (TAP1) polymorphism and asthma in Taiwanese population. To test
      whether TAP polymorphism has a role in the BPD, we investigated the association
      between TAP1 polymorphism and BPD by analyzing the results of genotype
      distribution. The study included 224 ventilated preterm infants (<30 weeks) who
      had respiratory distress syndrome (RDS) and needed intermittent mandatory
      ventilation (IMV) during Jan. 1999 to July 2003. The typing of TAP1 polymorphism
      was performed by polymerase chain reaction (PCR)-based restriction analysis. The
      demography between two groups of these ventilated preterm infants was not
      different. We observed no significant differences in genotype distribution or
      allele frequency of the TAPI polymorphisms between BPD and their respective
      control infants. There was also no significant difference in genotype
      distribution of the TAP1 polymorphism with duration of IMV. Therefor, we conclude
      that TAP1 polymorphism is not a useful marker for predicting the susceptibility
      or severity to BPD for Taiwanese.

PMID- 16640036
TI  - The recommended frequency of echocardiography in follow-up evaluation of patients
      with Kawasaki disease.
AB  - To assess the value of follow-up echocardiograms for patients with Kawasaki
      disease (KD). During a period of 5 years, children diagnosed with KD were
      enrolled in this study if at least three echocardiograms were documented,
      including one at admission, one at 1 to 2 months and one beyond 2 months
      following the onset of fever. The cohort study recruited 176 patients, and 120
      patients were included in the final analysis. Most (116 patients, 97%) of the
      patients were under 5 years of age, and the male-to-female ratio was 1.93: 1.
      During the study period, KD was more common during the summer (35.8%). Of the 120
      patients, 67 (56%) had normal echocardiograms, and 53 (44%) had abnormal
      echocardiograms at admission. Of the 53 patients with abnormal echocardiograms,
      35 had coronary artery dilatation, and 18 had aneurysm. The mean interval between
      the onset of illness and the documentation of echocardiographic abnormality was
      13 days (range 3-37 days). The abnormal echocardiographic findings resolved in 48
      of the 53 (90%) patients in 2 years. No patient who had normal echocardiographic
      findings at 1-2 months developed subsequent abnormalities. There was no
      difference in the proportion of persistent abnormal follow-up echocardiographic
      findings in patients with initial coronary dilatation or aneurysm between the 2m
      6m and 6m-12m follow-up echocardiograms (p = 0.78, p = 0.09, respectively). The
      proportion of patients with echocardiographic findings of coronary dilatation and
      aneurysm changed significantly between the 2m-6m and 12m-18m follow-up
      echocardiograms (p = 0.007, p = 0.045, respectively). Additional
      echocardiographic studies beyond 8 weeks for coronary artery morphology are not
      necessary if previous studies have produced normal results in patients with KD.
      Patients who have coronary artery abnormalities at the acute or subacute stage
      should receive an additional follow-up echocardiogram one year after the
      convalescent stage of the disease.

PMID- 16640037
TI  - Allogeneic related bone marrow transplantation in children--a single center
      experience.
AB  - We report our single-center experience with related allogeneic bone marrow
      transplantation (BMT) in pediatric recipients between April 1998 and December
      2004. Allogeneic bone marrow grafts from 19 donors (18 human leukocyte antigen
      (HLA)-matched sibling donors and 1 one antigen-mismatched related donor) were
      transplanted into patients aged 3-17 years (16 with leukemia and 3 with non
      malignant disease). The patients received a cell dose, with median total
      nucleated cell dose of 3.9 x 10(8)/kg (range, 0.7 - 8.7 x 10(8)) and median CD
      34+ cell dose of 3.0 x 10(6)/g (range, 0.3 - 9.8 x 10(6)). Seventeen patients
      (89.4%) engrafted after a median of 19 days (range 14-20 days). Acute graft
      versus host disease (GVHD) grade II to IV developed in 8 patients (42. 1%), and
      limited chronic GVHD developed in 2 evaluable patients (10.5%). Twelve of the 19
      patients were alive at a median follow-up of 1460 days (range, 270-2260 days).
      Full chimeric hematopoiesis was maintained in 11 of these 12 patients. Six
      patients (31.6%) had relapse of their underlying malignant disease, and one of
      them is still alive. Seven patients died (5 because of relapse and/or disease
      progression and 2 because of infectious complication). The underlying diseases
      were acute lymphoblastic leukemia (ALL; 4 cases: 3 CR2, 1 Ph+), acute myeloid
      leukemia (AML; 2 cases: 1 CR2, 1 refractory), and juvenile chronic myelogenous
      leukemia (JCML; 1 case). Relapsed leukemia at an extramedullary site occurred in
      2 patients with ALL after BMT. Although our data should be interpreted cautiously
      considering the limited number of patients, isolated extramedullary relapse seems
      to be common after allogeneic BMT.

PMID- 16640038
TI  - Urinary tract infections in young infants with prolonged jaundice.
AB  - The incidence of urinary tract infections (UTIs) in young infants with jaundice
      is low, and prolonged jaundice in that setting is even rarer. In this study, we
      retrospectively reviewed the clinical features of 50 infants (seen from 1984
      through 2004) 1 week to 3 months of age who had UTIs and prolonged jaundice and
      compared them with those of infants with UTIs in a similar age range at our
      hospital from a published study. The infants in our study had a lower incidence
      of high fever (12%), were less likely to have pyuria (29%), had fewer Escherichia
      coli but more Enterococcus species infections, and had more mixed infections
      (32%) than did the historical control. Klebsiella pneumoniae or Enterococcus
      species dominated in mixed infections (15/16) but the frequency of E. coli
      isolates did not differ significantly between mixed and single infections. We
      conclude that high fever and pyuria are unreliable criteria for screening for
      UTIs in young infants presenting with prolonged jaundice. Urine cultures should
      be obtained in such patients to determine whether a UTI is present. Mixed urinary
      infections, particularly K. pneumoniae and Enterococcus species, may play a key
      role in this entity.

PMID- 16640039
TI  - A survey of parental consent process for newborn screening in Taiwan.
AB  - Recent technological developments in newborn screening (NBS) allow many
      genetic/metabolic disorders to be detected pre-symptomatically even though they
      may be untreatable. Thus, current NBS faces ethical, legal, and social
      challenges. Obtaining parental consent for NBS demonstrates respect for and
      educates parents. The purpose of this study was to explore current practices in
      obtaining parental consent to conduct NBS in Taiwan. A self-administered
      questionnaire was mailed to obstetric clinicslhospitals (N=339) and 204
      questionnaires were returned for a response rate of 60.2%. Parental consent
      processes for NBS were divided into three categories-informed consent, informed
      refusal, and no informedlconsent. Between 66.7-67.6% clinics/hospitals used an
      "informed consent" model for all NBS items. Although most clinics/hospitals
      frequently informed parents before screening was conducted, the information given
      was often incomplete. Moreover, a "no informedl consent" model was used for
      congenital adrenal hyperplasia (CAH) and rare geneticlmetabolic disorders in
      between 22.5% and 25.1% of the clinics/hospitals, respectively. A total of 23.1%
      of clinics/hospitals chose an "informed refusal" model for the five traditional
      genetic/metabolic disorders. Using logistic regression analysis, the parental
      consent process for the five traditional disorders was found to have significant
      associations with the classification of the hospitals and the contracted NBS
      center (p < 0.01). Regional hospitals less frequently used the "informed consent"
      model than local clinics, and the clinics/hospitals that contracted with National
      Taiwan University Hospital were more likely to follow an "informed consent" model
      rather than those contracted with Taipei Institute Pathology. Establishing
      specific guidelines to regulate the parental consent process and educate medical
      personnel is crucial.

PMID- 16640040
TI  - Bilateral lung abscesses due to pseudomonas aeruginosa infection after open heart
      surgery in an infant: report of one case.
AB  - Lung abscess is an infrequent but serious problem in children. Bilateral lung
      abscesses occur even less commonly. We experienced a case of bilateral
      Pseudomonas aeruginosa lung abscesses in a 2-month-old infant after open heart
      surgery for interrupted aortic arch. The clinical and radiographic
      manifestations, together with treatment responses, are described in the following
      case report.

PMID- 16640041
TI  - Pseudohypoparathyroidism: report of seven cases.
AB  - Pseudohypoparathyroidism (PHP) is a rare inherited syndrome with several types.
      We reviewed the cases of 7 PHP patients seen between 1990 and 2003, and analyzed
      their clinical, biochemical data and long-term medical outcomes. Six boys and one
      girl were included. Two siblings showed Albright's hereditary osteodystrophy
      (AHO) and PHP Ia was impressed. The rest were suspected of PHP Ib. Their mean
      diagnosed age was 10.8 years and most had symptoms onset for several years before
      diagnosis. The most frequent initial presentations were seizure, followed by
      extremity muscle spasm, short stature, learning disability and psychomotor
      retardation. Mild thyrotropin elevation was noted in two patients of PHPIa. Early
      puberty onset, combined with bone age advancement was noted in the boy with PHP
      Ia, who had the shortest predicted adult height (PAH) (139.5 cm). The other 5
      boys had normal PAH, mean 171.42 cm, and 4 male patients reached final height
      with a mean of 163.25 cm, close to their target heights. During treatment, 2
      patients developed nephrocalcinosis. In conclusion, subtypes of PHP present
      heterogeneous phenotypes. Non-Ia subtypes might not be rare in Taiwan. Therefore,
      in hypocalcemic patients with mild high or normal parathyroid hormone (PTH), even
      in the absence of AHO, PHP should be ruled out. Regular renal sonography follow
      up is recommended during therapy.

PMID- 16640042
TI  - Hemolytic uremic syndrome associated with invasive Streptococcus pneumoniae
      infection: report of one case.
AB  - Hemolytic uremic syndrome (HUS) most commonly follows an episode of
      gastroenteritis associated with Escherichia coli (O157:H7). S. pneumoniae
      associated HUS is rare and has been reported having a high morbidity and
      mortality rate. We present a 1-year-5-month-old girl who developed S. pneumoniae
      associated HUS and positive T-activation testing. She received antibiotics,
      washed red blood cell transfusion and early continuous venovenous
      hemodiafiltration treatment. She had chronic renal failure but was without other
      sequelae after 8 months, follow-up. Early dialysis intervention in S. pneumoiae
      induced HUS patients decreasing the morbidity and mortality rate is discussed,
      and the literature is reviewed.

PMID- 16640043
TI  - Acute intoxication of lidocaine and chlorpheniramine: report of one case.
AB  - A case of acute intoxication involving lidocaine and chlorpheniramine (an
      antihistamine) in a 13-month-old child after ingestion of a commercial topical
      agent is presented. The major toxic reaction consisted of convulsion, coma,
      tachycardia, fever, and fatigue. This report shows that parents and physicians
      should be made aware of the hazards of lidocaine and overdose of other topical
      agents in infants and children.

PMID- 16640044
TI  - Renal cell carcinoma presented as fever of unknown origin: report of one case.
AB  - A 10-year-old girl, with an intermittent fever for 15 days, visited our emergency
      department. Initial work-up revealed no signs of infection and no palpable
      abdominal mass. KUB showed only displaced bowel gas. Abdominal ultrasound was
      performed which disclosed a huge mass at the lower pole of the right kidney.
      Abdominal computed tomography (CT) confirmed a huge, heterogeneous mass arising
      from the right kidney and without involvement of regional lymph nodes and
      inferior vena cava. Radical nephrectomy was performed and Stage 2 renal cell
      carcinoma (RCC) was confirmed. Fever subsided spontaneously after operation. No
      local recurrence or distant metastasis was detected in the following 3 years.
      Thus, occult malignant neoplasm as infrequent as RCC should be in the list of
      differential diagnoses of fever of unknown origin (FUO). An abdominal ultrasound
      is a useful screening tool for early diagnosis of RCC.

PMID- 16640045
TI  - [Bilateral retinal vasculitis with arterial aneurysms].
AB  - The authors reported unusual and rare condition of bilateral retinal vasculitis
      primarily affecting the central retinal artery at the nerve head and its 4 main
      branches. The most striking feature was the presence of the diffuse vitreous
      cells, occlusion of branch retinal artery, segmental periarterial infiltration,
      arterial sheating, retinal arterial aneurysms, disc swelling, peripheral retinal
      non perfusion and their complications. During 13 year's observation and treatment
      one eye went blind 3 years after initial examination. Second eye started the same
      clinical course two years after beginning of the disease. To avoid similar
      devastating course of the disease we started systemic steroids and
      immunosuppressive therapy, followed by photocoagulation of nonperfused peripheral
      retina and vitreoretinal surgery. We achieved stabilization of the disease with
      decreased visual functions. Comprehensive systemic work-up was unrevealing, no
      clear etiology was identified and diagnosis of idiopathic retinal vasculitis was
      made.

PMID- 16640046
TI  - [Iris racemose vascular anomalies].
AB  - Authors present 7 rare iris racemose vascular anomalies that were discovered by
      biomicroscopy during routine ocular examination. The morphology, clinical
      features and iris circulation of these cases are documented by iris
      fluoroangiography. They also report common features, some specific details of
      arrangement and classification criteria. The iris vascular anomaly appears to be
      benign stationary condition that has none systemic and ocular associations.

PMID- 16640047
TI  - [The orbital implant after exenteration of the orbit with the preservation of the
      eyelids and the conjunctival sac].
AB  - In ophthalmology, the orbital exenteration presents the most mutilating surgical
      procedure. The surgical technique presented by authors, preserves the eyelids and
      conjunctival sac. This surgical procedure was suggested and repeatedly performed
      in adult patients with extensive benign tumors (mostly meningeomas) by J.
      Otradovec and J. Safar. The enucleation of the eyeball preceded this type of
      surgery. The final state made it possible to put the prosthesis into the
      conjunctival sac. Today we inform about further development of this surgical
      technique and according to our own experiences we widen its indications to some
      malignant tumors (rhabdomyosarcoma and metastases of the retinoblastoma, etc.) in
      children. The initial cutaneous incision starts in the eyebrow area and is
      directed toward the bone of the orbital rim. The preparation of the tissue
      underneath the intact conjunctival sac to the lower aspect of the bone orbital
      rim follows. After folding the conjuctival-cutaneous sac back, the real content
      of the orbit is exenterated in the classical manner. After the hemostasis in the
      orbital apex, the flap is returned to its primary position and suturing of the
      primary incision in anatomical layers terminates the surgery. The authors refer
      about a boy, now 17 years old, who underwent at the age of three years the
      exenteration of the orbit in this manner due to a rhabdomyosarcoma. The authors
      also refer about the development and application of a special type of prosthesis
      made from silicone rubber--implant grade--filling out the orbital space and
      forming the anterior segment of the eye. The prosthesis was created from a
      classical orbital implant, regularly used in enucleation surgery and a
      conjunctival implant, a convex-concave plate with diameter of 20 mm. Both parts
      are made from the same type of silicon rubber and were connected together by
      vulcanization. The orbital implant was eliptically extended according to the
      measurements of the orbital casting made from dental impression matter. The
      cosmetic part, simulating the colored iris and the pupil, was prepared from a
      polyester sheet, painted with acrylic paint. It was fixated on the conjunctival
      prosthesis and covered with a transparent silicone foil. For the first time, the
      prosthesis was applied at the age of seven years, and during the next ten-years
      period, it was three times exchanged mostly for a bigger model. This procedure
      guaranteed proper growing of the orbital area and symmetrical development of the
      face. The prosthesis also carries out the prosthetic role and cosmetically it
      looks similarly like after the enucleation without the implant.

PMID- 16640048
TI  - [Optical coherence tomography in pars plana vitrectomy for idiopathic macular
      hole].
AB  - 26 eyes of 25 patients after macular hole surgery were followed-up for 6 months
      in average (range of 2-25 months). The overall anatomic success rate was 77 %.
      The internal limiting membrane was peeled after its staining with trypan blue in
      all closed macular holes. The macular hole surgery resulted in anatomic success
      of stage Ib or II in 11 (100 %) eyes, of stage III in 7 (64 %) eyes and in stage
      IV in 2 (50 %) eyes. There was an improvement or a stabilisation of the best
      corrected visual acuity (BCVA) in 85 %. BCVA improved from 4/20 to 4/12 in
      average. 45 % of patients with closed macular hole attained BCVA 4/10 or better,
      5 (25 %) of them with the best visual acuity at presentation improved to 4/8 in
      average. In 23 % cases of clinically normal fellow eyes, optical coherence
      tomography (OCT) detected an abnormality of the vitreoretinal surface. OCT is
      essential for evaluation of anatomical success after macular hole surgery. It is
      necessary to perform it also in a fellow eye to exclude clinically silent
      abnormality of the vitreoretinal surface.

PMID- 16640049
TI  - [Computer modeling correlation between the entering wound and the final position
      of the metallic intraocular foreign body].
AB  - AIM: The aim of this study was to establish the correlation coefficient between
      given parameters of the entering wound and final position of the metallic
      intraocular foreign body. MATERIAL AND METHODS: Fifty patients (50 eyes) with a
      penetrating injury of the eye and present metallic intraocular foreign body were
      included in this study. Clinically found data of the entering wound and final
      position of the intraocular foreign body (IFB) as well were transformed with a
      computer model into the three-dimensional parameters. Both parameters were
      statistically evaluated by means of correlation analysis, and correlation
      coefficient and determination coefficient were calculated. RESULTS: The extent of
      correlation between two variables is called correlation coefficient. The
      coefficient values range between -1 to +1. The closer is the calculated value to
      ranges (to -1 or to +1) the more are the two variables more correlated. The
      coefficient of determination values range from 0 to +1. The closer the results
      are to +1, the better the model describes the dependence between the two
      variables. The results obtained by means of correlation analysis were for the
      correlation coefficient 0.454, and for the coefficient of determination 0.6411
      respectively. CONCLUSION: Results of the correlation analysis show that the
      knowledge of coordinates of the entering wound has no prediction value for final
      position of the foreign body in the eye. These two variables are not correlated
      and so the accurate final position of the foreign body cannot be predicted. The
      final position of the intraocular metallic foreign body is probably influenced by
      biophysical factors not included in this study.

PMID- 16640050
TI  - [Contribution to differential diagnosis of intraocular tumors--case report].
AB  - Authors present the possibilities of different examination methods in cases of
      intraocular expansions and specific diagnostic methods to determine the actual
      etiology of the intraocular process in the posterior segment in particular. Of
      special concern to authors are cases, as is e.g. vitreous hemorrhage, in whose
      the standard examination methods are not useful. Pars plana vitrectomy with
      intraocular biopsy of the tissue for histological and cytological examination is
      very effective method to determine the proper diagnosis. The case report concerns
      with a 58 years old woman with vitreous hemorrhage and suspect tumor-like lesion,
      diagnosed by means of ultrasound examination. The pars plana vitrectomy revealed
      extensive preretinal organized hemorrhage with intravitreal hemorrhage. Samples
      for cytological examination were taken.

PMID- 16640051
TI  - [The ultrasound findings in posttraumatic endophthalmitis].
AB  - The aim of this study was to evaluate the ultrasound findings in eyes with
      endophthalmitis following penetrating injury and to establish unfavorable
      predictive signs of this serious disease. In a retrospective study we evaluated
      findings in 7 eyes of 7 patients followed up because of posttraumatic
      endophthalmitis at the Department of Ophthalmology, School of Medicine, in
      Olomouc, Czech Republic, EU, during the period September 1999-December 2004. The
      mean age of the patients was 37.3 years (range 22-49 years). The mean duration of
      the period between the injury and the formation of the endophthalmitis was 8.4
      days (range 1-21 days). The visual acuity at the time of admittance was very low;
      it ranged between light perception and 1/60 (0,016 or 20/1200). All patients
      underwent diagnostic-therapeutic pars plana vitrectomy with vitreous samples
      taken for microbiological examination and intravitreal antibiotic application.
      The final visual acuity (VA) ranged from 1/60 (0,016 or 20/1200) to 6/12 (0.5 or
      20/40), so it was very variable and that gave us the possibility to follow the
      connection between the final VA and seriousness of the penetrating injury, and
      also with the interval between the emergence of the endophthalmitis and beginning
      of its treatment. During the ultrasound examination, the presence of membranes in
      the vitreous body, posterior vitreous detachment, thickening of the choroid,
      detachment of the choroid and detachment of the retina were of concern to us.
      Membranes were present in the vitreous in 5 eyes. Without membranes detected by
      the ultrasound, there were 2 eyes; in both of them the final VA was better than
      6/36 (0,1667 or 20/120). The posterior vitreous detachment was detected in 3
      eyes, and not detected in four eyes. We didn't find any connection between the
      final VA and posterior vitreous detachment. The thickening of the choroid was
      present at the ultrasound examination in all seven eyes. The detachment of the
      choroid was not found in any eye. The retina was detached in two eyes. In three
      eyes only, the final central VA was better than 6/36 (0.1667 or 20/120). In two
      of them, the intraocular foreign body was found and in both the bacteria
      Staphylococcus epidermidis was detected. In the third eye, the soil bacteria
      Enterococcus and Klebsiela were cultivated. The ultrasound findings in these
      three eyes are identical only in the term of thickening of the choroid, similar
      to other eyes. In two of them no membranes were detected by ultrasound and no
      posterior vitreous detachment was found. The ultrasound examination in eyes with
      endophthalmitis after penetrating injury is specific in particular because of the
      mechanism of the injury. In contrast to the cases of the postoperative
      endophthalmitis, no prognostic unfavorable sings in the ultrasound examination
      can be strictly identified.

PMID- 16640052
TI  - [The influence of IOL implantation on visual acuity, contrast sensitivity and
      colour vision 2 and 4 months after cataract surgery].
AB  - PURPOSE: To assess the change in visual acuity, contrast sensitivity and colour
      vision in relation to the time after cataract surgery and to the type of
      implanted IOL, and to compare visual functions by patients with one and two
      pseudophakic eyes. METHODS: 45 cataract patients were examined before and then 2
      and 4 month after the cataract surgery. Visual acuity (VA) was tested on logMAR
      optotype chart with Landolt rings, contrast sensitivity (CS) was tested on the
      Pelli-Robson chart and the SWCT chart. For colour vision (CV) testing, the
      standard Farnsworth D-15 test and the desaturated Lanthony D-15 test were used.
      The patients were divided into two groups--a group with one pseudophakic eye and
      a group with two pseudophakic eyes, and also according to the type of IOL--PMMA
      or hydrophobic acrylate that had been implanted. Control group was composed of
      phakic subjects with no ocular pathology. RESULTS: After the cataract surgery, in
      both groups there was a significant improvement in monocular and binocular VA (p
      < 0.05), in monocular and binocular CS using both types of charts--Pelli-Robson
      (p < 0.05) and SWCT in all the spatial frequencies (p < 0.05). Also, a
      significant decrease in the number of minor errors in the standard Farnsworth D
      15 test (p < 0.05) as well as a substantial decrease in the number of minor and
      major errors in the desaturated Lanthony D-15 test (p < 0.05) and an overall
      improvement of CV (p < 0.05) were detected. There was no difference between the
      results 2 and 4 month after the surgery, except for CS in 12 c/deg (p < 0.05).
      The patients with two pseudophakic eyes had postoperatively better binocular VA
      and CS in the spatial frequencies of 12 c/deg and 18 c/deg and attained
      postoperative values comparable to those of control subjects. No significant
      difference in VA, CS or CV was found between the PMMA and hydrophobic acrylate
      intraocular lenses. CONCLUSION: After the cataract surgery, the visual functions
      tested by means of psychophysical methods of VA, CS and CV significantly improve
      and are stable 2 month after the surgery. The second eye surgery improves
      binocular visual functions the level of which doesn't differ from that of normal
      phakic subjects. There was no influence of the type of IOL on final state of VA,
      CS or CV.

PMID- 16640053
TI  - [Vernal keratoconjunctivitis and possibilities its treatment].
AB  - The authors present a case of vernal keratoconjunctivitis (VKC) in 5 years old
      boy. Despite intensive topical pharmacological therapy (mast-cell stabilizers,
      antihistamines, steroids in acute exacerbations) unsatisfied reduction of the
      symptoms was observed and cornea became involved in the left eye (LE). Repeated
      surgical abrasion of the papillary hypertrophy was performed with temporaly
      relief. We decided to provide a cryocoagulation of the papillary hypertrophy in
      the LE. We did not see any pre and post operative complications, significant
      improvement was observed and the patient is now (13 months after the surgery) in
      a good condition, on mast cell stabilizers only.

PMID- 16640054
TI  - [Women only 100 years ago were still embarrassed to wear eyeglasses. Dr. Alice
      Masarykova 3 May 1879--26 November 1966].

PMID- 16640055
TI  - Meniere's disease.

PMID- 16640056
TI  - Problems and solutions for fitting amplification to patients with Meniere's
      disease.
AB  - Fitting amplification to a patient with Meniere's disease (MD) can present
      several challenges to the dispensing audiologist. These challenges include the
      presence of fluctuating hearing loss, a rising audiometric configuration,
      unilateral or asymmetrical hearing loss, reduced dynamic range, and reduced word
      recognition scores. The presence of any one of these characteristics could create
      obstacles for a successful hearing aid fit. The presence of most if not all of
      these characteristics in a single patient can readily challenge the skills of
      even the most experienced dispensing audiologist. In addition to the audiometric
      challenges, this patient population has the added psychological problems
      associated with feeling ill due to the nausea secondary to vertiginous attacks
      and the anxiety associated with the unpredictable nature of the course of these
      attacks. This paper summarizes numerous strategies and technologies that could be
      implemented by the audiologist to address these unique challenges and provide a
      greater opportunity for a successful hearing aid fit. These suggestions include
      (1) advantages offered by digital signal processing; (2) using directional
      microphones and assistive listening devices to improve speech recognition in
      noise; (3) using wireless hearing aids as well as the bone anchored hearing aid;
      (4) counseling patients on the realistic expectations from amplification in noisy
      listening situations and for those with poor speech recognition; (5) using
      multiple programs for patients with fluctuating hearing loss; and (6) offering
      suggestions on programming the frequency-gain/output response for a rising
      configuration.

PMID- 16640057
TI  - Meniere's disease review 2005.
AB  - Meniere's disease (MD) is a complex, multifactorial disorder of the inner ear
      that is the most common cause of the syndrome of episodic vertigo combined with
      fluctuating hearing loss. In spite of a century of investigation, the etiology
      and pathophysiology of MD remain controversial and incompletely understood. Among
      the factors that have contributed to these controversies are the absence of (1) a
      validated clinical test, (2) an appropriate animal model, and (3) a specific
      treatment. Nonetheless, physicians are able to assist MD patients with a variety
      of tailored, symptom-specific medications and therapies. Given that the vertigo
      induced by MD, in general, is self-limited, the long-term outlook for balance
      function is good. The same cannot be said for the hearing dysfunction of MD.

PMID- 16640058
TI  - Evaluating treatments for Meniere's disease: controversies surrounding placebo
      control.
AB  - Although double-blind experimental designs are considered the gold standard for
      documenting treatment effectiveness, many treatments for Meniere's disease have
      not been evaluated using this methodology. Particularly with a disease
      characterized by exacerbation and remission, carefully controlled, long-term
      studies are required. The nature of the placebo effect is described in this
      article, and the concept of debonafide effect introduced. Ideally, patients
      should be given treatments supported by evidence-based medicine that have the
      lowest possible risk of side effects. However, risk minimization may dictate
      using treatments that have not been proven effective and may evoke debonafide
      effects.

PMID- 16640059
TI  - An update on the surgical treatment of Meniere's diseases.
AB  - Various surgical procedures have evolved for the treatment of Meniere's disease
      patients who are refractory to medical therapy. These can be in the form of
      conservative surgeries as in endolymphatic sac surgery or in the form of
      destructive procedures. The latter include labyrinthectomy and vestibular nerve
      section, which result in deafferentation of the vestibular end organ. In the past
      decade, intratympanic therapy with gentamycin and steroids has evolved as new
      methods for the treatment of Meniere's disease. The literature witnesses
      controversies in the effectiveness of endolymphatic sac surgery in the treatment
      of Meniere's disease. The choice of the surgical procedure depends on the degree
      of serviceable hearing, the severity of the spells, and the condition of the
      contralateral ear. The most commonly used procedures in the treatment of
      Meniere's disease and their indications are reviewed.

PMID- 16640060
TI  - Electrocochleography in the evaluation of patients with Meniere's
      disease/endolymphatic hydrops.
AB  - Electrocochleography (ECochG) has evolved as an important tool in the
      diagnosis/assessment/monitoring of Meniere's disease/endolymphatic hydrops
      (MD/ELH). This manuscript provides an update on the use of ECochG for these
      purposes. The material presented includes descriptions of the components of the
      electrocochleogram; ECochG recording approaches and parameters; how to prepare
      for an exam, including subject/patient considerations; construction and placement
      of a tympanic membrane recording electrode; and interpretation the
      electrocochleogram. Various approaches aimed at improving ECochG's sensitivity
      and specificity to MD/ELH also are described. These approaches go beyond simple
      measurement of the now-conventional summating potential (SP)/action potential
      (AP) magnitude ratio to include the SP magnitude to tonebursts, the SP/AP area
      ratio, and the AP latency difference to clicks of opposing polarity.

PMID- 16640061
TI  - Differentiation of Meniere's disease and migraine-associated dizziness: a review.
AB  - A significant body of literature exists demonstrating a relationship between
      migraine disorders and dizziness. In the characterizations of the migraine
      associated dizziness, the signs and symptoms show overlap with those
      characterizing Meniere's disease. There has been literature, beginning with
      Meniere himself, suggesting a relationship between Meniere's disease and migraine
      associated dizziness. This implicates a possible underlying link in pathogenesis.
      This review article presents a discussion of the overlap in signs and symptoms
      between the two disorders. Suggestions for differentiating between the disorders
      based on recent literature protocols and use of test results are also discussed.
      Vestibular and balance rehabilitation programs have a role in both of the
      disorders but differ in the overall management aspects of the disorders. The
      distinction in the use of vestibular rehabilitation is discussed.

PMID- 16640062
TI  - Positional nystagmus of central origin.
AB  - Audiometric, electrophysiologic, and radiographic findings for a 68-year-old male
      with an "imbalance" concern are presented. This paper has a two-fold purpose: (1)
      to present an unusual electronystagmography case study and (2) to highlight the
      importance of test conditions in lesion localization. The specific disease
      pathophysiology remains obscure. Repeated hearing tests documented a known
      hearing impairment with worsening word-recognition ability of the right ear. An
      initial electronystagmographic exam was normal except for a mild ageotropic
      direction-changing positional nystagmus with eyes open and fixed. No repeatable
      click-evoked auditory brainstem response waveforms could be collected. A magnetic
      resonance imaging of the brain documents diffuse ischemic white matter disease. A
      repeated vestibular examination some months later supports the initial findings.
      The case illustrates the importance of following diagnostic protocol, of repeated
      measures, and of using both a visual fixation and a nonfixation condition for
      select electronystagmographic subtests.

PMID- 16640063
TI  - Objective detection of auditory steady-state responses: comparison of one-sample
      and q-sample tests.
AB  - Auditory steady-state responses (ASSR) are expected to be useful for the
      objective, frequency-specific assessment of hearing thresholds in small children.
      To detect ASSR close to the hearing threshold, a powerful statistical test has to
      be applied. At present, so-called one-sample tests are used. These tests only
      evaluate the phase, or the phase and amplitude, of the first harmonic, that is,
      the fundamental frequency. It is shown that higher harmonics with significant
      amplitudes are also contained in the ASSR spectrum. For this reason, statistical
      tests that only consider the first harmonic ignore a significant portion of the
      available information. The use of a q-sample test, which, in addition to the
      fundamental frequency, also includes higher harmonics in the detection leads to a
      better detection performance. The evaluation of test performance uses both
      detection rate and detection time.

PMID- 16640064
TI  - Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy.
AB  - A controlled clinical study was conducted to evaluate prospectively the clinical
      efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in
      military veterans having clinically significant tinnitus. Qualifying patients
      were placed into the two groups in an alternating manner (to avoid selection
      bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of
      treatment were evaluated using three self-administered tinnitus questionnaires
      (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity
      Index) and the verbally administered TRT interview forms. Findings are presented
      from the three written questionnaires, and from two of the interview questions
      (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on
      an intent-to-treat basis, using a multilevel modeling approach. Of the 123
      patients enrolled, 118 were included in the analysis. Both groups showed
      significant declines (improvements) on these measures, with the TRT decline being
      significantly greater than for TM. The greater declines in TRT compared to TM
      occurred most strongly in patients who began treatment with a "very big" tinnitus
      problem. When patients began treatment with a "moderate" tinnitus problem, the
      benefits of TRT compared to TM were more modest.

PMID- 16640065
TI  - Cochlear implant speech processor placement and compression effects on sound
      sensitivity and interaural level difference.
AB  - The purpose of this investigation was to determine the impact of commonly
      recommended cochlear implant (CI) speech processor placements on microphone
      output both with and without single channel front-end compression. The impact of
      this compression use on interaural level difference (ILD) magnitude was also
      evaluated for the ear-level position. Finally, pilot localization data collected
      with and without single channel front-end compression was collected on seven
      bilateral cochlear implant recipients. The results revealed that differences in
      signal audibility due to clinical placement of CI speech processors in ear,
      shoulder, and collar positions can at least partially be offset through the use
      of front-end compression. These data also revealed that compression impacted ILD
      cues. Preliminary data indicated that some bilaterally implanted subjects were
      able to take advantage of the enhanced ILD cues when compression was turned off,
      while other bilaterally implanted subjects did not localize better in the
      compression-off condition.

PMID- 16640066
TI  - The effect of speech presentation level on acceptance of background noise in
      listeners with normal hearing.
AB  - A method has been established to measure the maximum acceptable background noise
      level (BNL) for a listener, while listening to speech at the most comfortable
      listening level (MCL). The acceptable noise level (ANL) is the difference between
      BNL and MCL. In the present study, the ANL procedure was used to measure
      acceptance of noise, first, in the presence of speech at MCL and, then, for
      speech presented at much lower and higher levels in listeners with normal
      hearing. This study used the term ANL to describe the results obtained at MCL and
      also at other speech presentation levels. The mean ANL at MCL was 15.5 dB, which
      is comparable to results obtained by previous investigators. ANL increases
      systematically with speech presentation level. Mean ANLs ranged from 10.6 dB when
      speech was presented at 20 dB HL to 24.6 dB when speech was presented at 76 dB
      HL. The results indicated that the acceptance of noise depends significantly on
      speech presentation level.

PMID- 16640067
TI  - Auditory neuropathy: a biologically inappropriate label unless acoustic nerve
      involvement is documented.

PMID- 16640068
TI  - [Therapy for geriatric syndrome].

PMID- 16640069
TI  - [Prevention of and therapy for cerebral infarction in the aged].

PMID- 16640070
TI  - [Thermotherapy for heart failure in the aged].

PMID- 16640071
TI  - [Good life after stroke].

PMID- 16640072
TI  - [Kanpo medicine for the aged].

PMID- 16640073
TI  - [Anti-aging mechanism in centenarians].

PMID- 16640074
TI  - [Good Death].

PMID- 16640075
TI  - [Helicobacter pylori and stomach cancer].

PMID- 16640076
TI  - [Physicians' views on applicability and evaluation of liver transplantation].

PMID- 16640077
TI  - [Update on inflammatory bowel diseases].

PMID- 16640078
TI  - [Fulminant type-1 diabetes].

PMID- 16640079
TI  - [Secondary hypertension to endocrine diseases and electrolyte imbalance].

PMID- 16640080
TI  - [Diagnosis of and therapy for migraine].

PMID- 16640081
TI  - [Diagnosis of and therapy for lumbago].

PMID- 16640082
TI  - [New trends in therapy for arthritis rheumatoid].

PMID- 16640083
TI  - [Concept of and therapy for Fibromyalgia].

PMID- 16640084
TI  - [Physiopathology of and therapy for hypertrophic cardiomyopathy].

PMID- 16640085
TI  - [Recent topics on diagnosis and therapy for arrhythmia].

PMID- 16640086
TI  - [Future trends in clinical care of COPD].

PMID- 16640087
TI  - [Present status of and new trends in therapy for lung cancer].

PMID- 16640089
TI  - [Diagnosis of and therapeutic strategy for myelodysplastic syndrome].

PMID- 16640088
TI  - [Recent progress in therapy for hematological malignancies].

PMID- 16640090
TI  - [Hyperuricemia and kidney failure].

PMID- 16640091
TI  - [Diagnosis of and therapy for bacterial infections].

PMID- 16640092
TI  - [The Practice Guidelines 2000 for cardiopulmonary resuscitation].

PMID- 16640093
TI  - [Public accessibility to the journal of Internal Medicine through J-STAGE ].

PMID- 16640094
TI  - Eligibility for and outcome of hepatitis C treatment of HIV-coinfected
      individuals in clinical practice: the Swiss HIV cohort study.
AB  - BACKGROUND: Morbidity and mortality of individuals co-infected with HIV and
      hepatitis C virus (HCV) is often determined by the course of their HCV infection.
      Only a selected proportion of those in need of HCV treatment are studied in
      randomized controlled trials (RCTs). We analysed the prevalence of HCV infection
      in a large cohort, the number of individuals requiring treatment, the eligibility
      for HCV treatment, and the outcome of the combination therapy with pegylated
      interferon-a and ribavirin in routine practice. METHODS: We analysed prescription
      patterns of HCV treatment and treatment outcomes among participants from the
      Swiss HIV Cohort Study with detectable hepatitis C viraemia (between January 2001
      and October 2004). Efficacy was measured by the number of patients with
      undetectable HCV RNA at the end of therapy (EOTR) and at 6 months after treatment
      termination (SVR). Intention-to-continue-treatment principles were used. RESULTS:
      A total of 2150 of 7048 (30.5%) participants were coinfected with HCV; HCV RNA
      was detected in 60%, and not assessed in 26% of HCV-antibody-positive
      individuals. One hundred and sixty (12.5%) of HCV-RNA-positive patients started
      treatment. In patients infected with HCV genotypes 1/4 or 2/3, EOTR was achieved
      in 43.3% and 81.2% of patients, respectively, and SVR rates were 28.4% and 51.8%,
      respectively. More than 50% of the HCV-treated patients would have been excluded
      from two large published RCTs due to demographic, clinical and laboratory
      criteria. CONCLUSIONS: Despite clinical and psychosocial obstacles encountered in
      clinical practice, HCV treatment in HIV-coinfected individuals is feasible with
      results similar to those obtained in RCTs.

PMID- 16640095
TI  - Low genetic barrier to large increases in HIV-1 cross-resistance to protease
      inhibitors during salvage therapy.
AB  - HIV-1 resistance to protease inhibitors (PIs) is characterized by extensive cross
      resistance within this drug class. Some PIs, however, appear less affected by
      cross-resistance and are often prescribed in salvage therapy regimens for
      patients who have failed previous PI treatment. To examine the capacity of HIV-1
      to adapt to these treatment changes, we have followed the evolution of HIV-1
      protease genotypes and phenotypes in 21 protease-inhibitor-experienced patients
      in whom 26 weeks of an aggressive salvage regimen associating lopinavir,
      amprenavir and ritonavir failed to suppress viral replication. Baseline genotypes
      exhibited a median of seven resistance mutations in the protease. After 26 weeks
      of treatment, changes in protease genotypes were seen in 13/21 patients. The
      evolution of these protease genotypes was rapid, with more than one-third of the
      changes occurring during the first 6 weeks. Although the mean number of
      additional mutations was small (2.15 new mutations at week 26) these mutations
      were sufficient to promote remarkable changes in resistance phenotype. In several
      patients, some of the new mutations were found to exist before salvage treatment
      as part of minority quasi-species. Thus, in the face of the strong
      pharmacological pressure exerted by combinations of PIs to which it has never
      been exposed, and in spite of limited cross-resistance to these drugs before
      salvage therapy, HIV-1 can rapidly adapt its resistance genotype and phenotype at
      a minimal evolutionary cost.

PMID- 16640096
TI  - The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype
      of zidovudine resistance mutations.
AB  - The HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir (TFV),
      abacavir, didanosine and stavudine can select for K65R, whereas zidovudine (AZT)
      and stavudine can select for thymidine analogue mutations (TAMs) in HIV-1 reverse
      transcriptase (RT). HIV-1 with TAMs shows reduced susceptibility to all NRTIs,
      most notably AZT, whereas HIV-1 with K65R shows reduced susceptibility to all
      NRTIs except AZT. K65R and TAMs rarely occur together in patients. However, when
      present together, K65R can restore susceptibility to AZT. This study
      characterizes the underlying mechanisms of resistance of these RT mutants to TFV
      and AZT. K65R mediated decreased binding/incorporation of TFV and AZT (increased
      Ki/Km of 7.1- and 4.3-fold, respectively), but also decreased excision of TFV and
      AZT (0.7- and 0.3-fold, respectively) when compared with wild-type RT. By
      contrast, TAMs mediated increased TFV and AZT excision (11- and 5.4-fold,
      respectively), and showed no changes in binding/incorporation. When these
      mutations were combined, K65R reversed TAM-mediated AZT resistance by strongly
      reducing AZT excision. Molecular modelling studies suggest that K65R creates
      additional hydrogen bonds that reduce the conformational mobility of RT,
      resulting in reduced polymerization and excision. Thus, consistent with clinical
      HIV-1 genotyping data, there appears to be no net NRTI resistance benefit for
      TAMs and K65R to develop together in patients taking AZT and TFV disoproxil
      fumarate, where the TAM pathway alone provides the greatest resistance for both
      drugs.

PMID- 16640097
TI  - The early HCV RNA dynamics in patients with acute hepatitis C treated with
      pegylated interferon-alpha2b.
AB  - Interferon and pegylated interferon (peg-IFN) are highly effective in patients
      with acute hepatitis caused by hepatitis C virus (acute hepatitis C, AHC), but
      the optimal timing of treatment is still under debate. In this open-labelled,
      uncontrolled trial, 19 patients with AHC, including 12 intravenous drug users
      (IVDUs), were treated early in the course of the infection with peg-IFN-alpha2b
      for 12 weeks. Diagnosis was made according to standardized criteria. The HCV RNA
      decay was analysed during the first 4 weeks of treatment by quantitative branched
      DNA and by qualitative RT-PCR. Of the patients, 11 (58%) had genotype 1.
      Sustained virological response (SVR) was achieved in 14 out of 19 patients (74%)
      and the mean time to achieve a negative RT-PCR for HCV RNA was 2.5 weeks. The SVR
      was associated by univariate analysis with peg-IFN dosage < or = 1.33
      microg/kg/week (P = 0.026) and HCV RNA level at onset of therapy (P = 0.017).
      Using a logistic regression model, only peg-IFN dosage > or = 1.33
      microg/kg/weekly was significantly associated with SVR (P = 0.0379, OR: 14.7; 95%
      CI: 1.16-185.2). The SVR was 100% and 83.3%, respectively, in genotype 1 and non
      1 infected patients treated with a dosage equal to or higher than 1.33 microg/kg,
      compared with 40% and 50%, respectively, in those who received a lower dosage.
      Efforts should be made to propose a 12-week treatment with peg-IFN-alpha2b for
      AHC, and to maximize peg-IFN dosage. Early treatment is associated with early
      disappearance of HCV RNA.

PMID- 16640098
TI  - Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of
      therapy: effects on CD4+ T-cell count and HIV-1 RNA load.
AB  - Sequence analysis of HIV-1 from 440 therapy-naive individuals included within the
      CASCADE study, who seroconverted within 18 months of the last negative test,
      identified 65 persons infected with a strain carrying resistance-associated
      mutations. Population-based sequencing was performed for 20 of these individuals
      during the therapy-free follow-up period. The median time of follow-up was 15
      months (interquartile range from 10 to 23 months). Of these individuals, 12
      showed subsequent evolution at the resistance positions, whereas the virus of 8
      people was stable during this period. In the reverse transcriptase (RT) gene, the
      drug-resistant 215Y or 215F codons evolved to alternative codons in all six
      cases, 70R reverted to the wild-type 70K in 3 of the 4 individuals, 67N evolved
      only in 1 of 4 patients to a wild-type 67D, 215S evolved to wild-type 215T in 1
      of 3 patients, 219N evolved to 219K in 1 of 2 patients, and one patient with 184V
      reversed to the wild-type 184M. The 181C variant evolved to the wild-type 181Y in
      1 of 2 individuals. These codon changes were caused by single nucleotide
      mutations. No evolution was observed for other RT mutations: 41L, 69D, 69N, 190S,
      210W, 215L, 215C, 215E and 219Q. In the protease gene, resistance mutations 84V
      and 90M were stable in 2 individuals. Comparing the CD4+ T-cell count of the 12
      evolving versus the 8 stable cases revealed no statistically significant
      difference at the date of the first sequence following seroconversion.
      Interestingly, a lower CD4+ T-cell count was observed in the group without
      evolution at the second sequence time point (P = 0.043). No difference in HIV-1
      RNA load was observed. These results, together with the apparent pressure to
      mutate at the resistance-associated positions exemplify the decreased fitness of
      viruses carrying 21 5Y/F, 70R or 184V.

PMID- 16640099
TI  - Evaluation of the HIV lipodystrophy case definition in a placebo-controlled, 144
      week study in antiretroviral-naive adults.
AB  - OBJECTIVE: To compare three versions of the objective HIV-associated
      lipodystrophy (HIVLD) case definition (LDCD) and derived severity scale to
      spontaneous clinical LD assessment in adults initiating antiretroviral therapy.
      DESIGN AND MAIN OUTCOME MEASURES: The LDCD versions were the 'primary' LDCD
      [which includes dual-energy X-ray absorptiometry (DXA) and computerized
      tomography (CT)], a simpler 'central' LDCD that omits CT data, and a simpler but
      probably less accurate 'non-imaging' LDCD. Physician LD assessments were
      passively reported. Two of the 10 parameters in the primary LDCD were not
      collected and were imputed. Setting, participants and interventions:
      Retrospective analysis of a randomized, placebo-controlled, 144-week study of
      tenofovir DF or stavudine (d4T) in 600 antiretroviral-naive adults. RESULTS:
      Central LDCD and clinical assessment diagnosed LD in 27% and 19% of d4T
      recipients at week 144, respectively (P < 0.001), and 3% and 3% of tenofovir DF
      recipients, respectively (P = 0.248). The central LDCD performed at least as well
      as the primary LDCD; both were more sensitive than the non-imaging model. There
      was poor concordance between clinical and LDCD-based diagnosis (kappa 0.02-0.20);
      most clinical cases did not fulfill any LDCD. Using the central LDCD, most LD was
      grade 1; 6% of d4T recipients and no tenofovir DF recipient had grade 3-4 LD at
      week 144 (P = 0.007). Independent risk factors for LD using the central LDCD were
      d4T, increasing age, female sex and higher baseline triglycerides, whereas
      clinical assessment consistently identified only d4T. The LDCD score was more
      sensitive than DXA for assessing LD severity. CONCLUSIONS: In this prospective
      study of a first antiretroviral regimen, the LDCD was more sensitive for LD
      diagnosis and identified more lipodystrophy risk factors than spontaneous
      clinical assessment or DXA, and also objectively quantified LD severity. The
      central LDCD should make objective LD assessment cheaper and simpler. Spontaneous
      clinical LD assessment of is of limited value, even in placebo-controlled trials.

PMID- 16640100
TI  - In combination, nucleoside reverse transcriptase inhibitors have significant
      effects on 3T3-L1 adipocyte lipid accumulation and survival.
AB  - The use of nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment
      of HIV infection is clearly linked to the development of subcutaneous fat
      atrophy. Until recently, however, in vitro studies of adipocytes have shown no or
      only modest and inconsistent effects of these agents on adipocyte biology. This
      is in contrast to the protease inhibitors (PIs), which are also linked to the
      development of HIV lipodystrophy. These agents have relatively consistent
      inhibitory effects on the differentiation of cultured adipocytes, and have
      occasionally been found to have other effects on adipocyte biology as well. We
      aimed to explore more thoroughly the effects of NRTIs and combinations of
      antiretroviral agents commonly used in clinical practice on multiple aspects of
      adipocyte biology using the 3T3-L1 adipocyte cell line. We found that when used
      individually, NRTIs decrease cell survival but only lamivudine significantly
      alters lipid accumulation. However, NRTI and dual NRTI-PI combinations do
      significantly decrease lipid accumulation in 3T3-L1 adipocytes, have a much
      greater detrimental impact on cell survival and decrease adipocyte
      differentiation.

PMID- 16640101
TI  - A multiphase model of the dynamics of HBV infection in HBeAg-negative patients
      during pegylated interferon-alpha2a, lamivudine and combination therapy.
AB  - Using a multiphase bio-mathematical model, we studied the dynamics of hepatitis B
      virus (HBV) infection in 72 HBeAg-negative patients who received 48 weeks of
      either lamivudine (3TC; 25 patients); pegylated interferon-alpha2a (peg-IFN
      alpha2a) 180 mg weekly plus 3TC (23 patients), or peg-IFN-alpha2a 180 mg weekly
      plus placebo (24 patients). During the first month of therapy most of the 3TC -/+
      peg-IFN-alpha2a treated patients showed a multiphase decay of viral load: during
      the first two phases, where we hypothesized a direct inhibition of virus
      production, the mean viral production per infected cell was reduced by 2.22 log10
      and 2.36 log10, respectively. At variance, peg-IFN-alpha2a treated patients had a
      biphasic profile: the first phase HBV DNA decline was slower than that observed
      in 3TC patients (mean HBV DNA t(1/2) = 1.6 +/- 1.1 days and 9.5 +/- 3.0 h,
      respectively) and the direct antiviral effect reduced virus production by 1.14
      log10. From day 14 onwards (third or second phase according to multi- or biphasic
      patterns), HBV DNA declined mainly because of the infected hepatocyte clearance
      that slowed down in approximately 50% of the patients from day 35, possibly
      because of a negative feedback on the immune system activity. Computing the
      number of infected cells at the end of therapy we found that peg-IFN-alpha2a and
      3TC monotherapy determined a similar reduction of infected hepatocytes (mean: 
      3.3 log10), whereas there was a greater reduction in combination therapy patients
      (-5.0 versus -3.3 log10, P = 0.039). In conclusion, peg-IFN-alpha2a, in spite of
      having direct antiviral activity lower than that of 3TC, achieved a comparable
      reduction of infected hepatocytes, possibly because of a higher infected cell
      clearance rate.

PMID- 16640102
TI  - Salvage therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected
      patients with multiple treatment failures: randomized ANRS 107 trial.
AB  - BACKGROUND: Ritonavir (RTV)-boosted atazanavir (ATV) and tenofovir disoproxil
      fumarate (TDF-DF) are promising in highly experienced patients because of their
      pharmacokinetic profile, activity, safety and resistance properties. METHODS: A
      26-week study of the safety and efficacy of RTV-boosted ATV plus TDF-DF was
      conducted in 53 HIV-infected patients who were failing their current highly
      active antiretroviral therapy (HAART) regimen. Patients with history of failure
      to at least two protease inhibitors (PIs) and one non-nucleoside reverse
      transcriptase inhibitor (NNRTI) were randomized to either continue their current
      regimen (group 1) or replace the PI by ATV (300 mg once daily) boosted by RTV
      (100 mg; group 2) for 2 weeks. Then, all patients received the same combination
      of ATV, RTV and TDF-DF (300 mg) plus optimized NRTIs regimen. RESULTS: At
      baseline, median CD4+ T-cell count was 206/mm3, median viral load (VL) 5.0
      log10/ml and median numbers of NRTI, NNRTI and PI resistance mutations were 7, 1
      and 8, respectively. At week 2, median VL remained unchanged from baseline in
      group 2 as compared with group 1 (-0.1 vs -0.1 log10/ml). At week 26, a mild
      decrease in median VL from baseline of 0.2 log10/ml was observed, with 16 (31%)
      and 9 (17%) patients exhibiting a decrease in viral load of at least 0.5 and 1.0
      log10/ml, respectively. Baseline phenotypic and genotypic resistance to ATV were
      the most predictive independent factors of virological response. The regimen was
      well tolerated. CONCLUSION: In these very advanced patients failing highly HAART,
      the combination of boosted ATV plus TDF-DF yielded low antiretroviral activity.

PMID- 16640103
TI  - Boosted versus unboosted indinavir with zidovudine and lamivudine in nucleoside
      pre-treated patients: a randomized, open-label trial with 112 weeks of follow-up
      (HIV-NAT 005).
AB  - INTRODUCTION: The use of HIV protease inhibitors (PIs) in a ritonavir (RTV)
      boosted form is now common. However, randomized data comparing boosted with
      unboosted PI strategies are scarce. METHODS: This randomized, open-label trial
      compared indinavir (IDV) 800 mg three times daily with IDV/RTV 800/100 mg twice
      daily, both given with zidovudine (AZT)/lamivudine (3TC) twice daily in
      individuals with at least 3 months previous AZT experience. The primary endpoint
      was the time-weighted average change in HIV RNA from baseline. Designed as a 48
      week study, follow-up continued until week 112. Primary analysis is by intention
      to treat. RESULTS: One hundred and three patients commenced therapy and are
      included in the analysis. Patients had a median of 29 months past nucleoside
      reverse transcriptase inhibitor (NRTI) exposure. Baseline median (interquartile
      range) log10 HIV RNA was 4.0 (3.3-4.5) and CD4+ T-cell count 166 (40-323)
      cells/microl. After 112-weeks of study there was no significant difference
      observed between arms in the mean (SD) change in time-weighted average HIV RNA
      from baseline (-1.6 [1.1] HIV RNA copies/week/ml three times daily arm; -1.4
      [1.1] HIV RNA copies/week/ml twice daily arm; P = 0.3). Both arms were associated
      with substantial toxicity expressed as serious adverse events and study drug
      interruptions. The twice daily arm experienced greater dyslipidaemia. Mean (SD)
      changes in time-weighted CD4+ T-cell count from baseline were similar [88 (84)
      cells/week/microl three times daily arm; 70 [109] cells/week/microl twice daily
      arm; P = 0.3). CONCLUSIONS: RTV-boosted IDV 800/100 mg twice daily demonstrated
      comparable efficacy to unboosted IDV 800 mg three times daily dosing. Both
      regimens were associated with substantial toxicity. Use of lower doses of RTV
      boosted IDV may result in better tolerability without loss of efficacy and
      warrant further research.

PMID- 16640104
TI  - Antiviral efficacy and genotypic resistance patterns of combination therapy with
      stavudine/tenofovir in highly active antiretroviral therapy experienced patients.
AB  - OBJECTIVES: To evaluate antiviral efficacy of stavudine/tenofovir (d4T/TDF)
      backbone combination in late-line antiretroviral therapy, and to assess clinical
      and virological determinants of treatment success. DESIGN: Multicentric
      retrospective analysis on patients starting d4T/TDF after highly active
      antiretroviral therapy (HAART) failure. METHODS: The primary endpoint was the
      change in plasma HIV-1 RNA from the baseline (time of d4T/TDF initiation) to 6
      months of therapy; secondary endpoint was the risk of virological failure.
      RESULTS: Among 172 patients included, a mean change in HIV-1 RNA of -1.69 (+1.23)
      and -1.53 (+1.43) log10 cp/ml was observed respectively at weeks 24 and 48 after
      starting d4T/TDF combination. Any single type-1 thymidine analogue mutation (TAM;
      M41L, L210W, T215Y) had a negative effort on the change in HIV RNA at 6 months,
      whereas among type-2 TAMs (D67N, K70R, K219Q), only D67N showed a trend for a
      negative effect. Presence of M184V mutation was related with a greater reduction
      in HIV RNA during d4T/TDF exposure. The risk of virological failure at 6 months
      after d4T/TDF starting was 22%. Type-1 TAMs were associated with a greater risk
      of failure (adjusted hazard ratio [HR]=1.65; 95% confidence interval [CI] 1.19
      2.29). Conversely, M184V showed a protective effect. In 17 genotypic tests
      available at failure, no K65R mutation was detected, whereas a trend for an
      increasing prevalence of d4T-associated mutations was found. CONCLUSIONS:
      Combining TDF with a thymidine analogue as d4T may be effective as component of
      antiretroviral rescue regimens in HIV-infected patients with previous exposure to
      nucleoside analogue reverse transcriptase inhibitor. Previous selection of type-1
      TAMs induces a detrimental effect over virological response.

PMID- 16640105
TI  - A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid
      interferon for HBeAg-positive chronic hepatitis B.
AB  - Combination therapy between two immunomodulators used for treatment of chronic
      hepatitis B was explored based on reported therapeutic efficacy of interferon
      alpha, and thymosin-alpha1 as monotherapeutic agents to determine if combination
      therapy was superior to interferon alone. This double-blinded, randomized,
      placebo-controlled trial compares the addition of thymosin-alpha1, 1.6 microg
      taken three times per week (combination therapy) or thymosin placebo
      (monotherapy) to lymphoblastoid interferon (Wellferon), 5 million international
      units (MIU) taken three times per week, for 24 weeks. Entry criteria included
      positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) > or =
      1.5 x upper normal limit, but < or = 10 x upper normal limit; positive HBV DNA;
      absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98
      HBeAg-positive patients were recruited, of which 48 were randomized to
      combination therapy and 50 to monotherapy. The primary endpoint was the loss of
      HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion,
      normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg
      loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively
      (difference, 17.8%; 95% CI -1.2%-35.3%, P = 0.067). There was a trend towards
      HBeAg loss when using combination therapy. There were also no statistically
      significant differences between the different therapies with respect to the
      secondary endpoints of HBeAg seroconversion, changes in histology, normalization
      of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement
      in HBeAg loss rates using combination therapy over interferon monotherapy. This
      could clinically indicate a potential important difference that would need
      confirmation in subsequent trials.

PMID- 16640106
TI  - Comparison of two different regimens of combined interferon-alpha2a and
      lamivudine therapy in children with chronic hepatitis B infection.
AB  - AIM: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN
      alpha2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. METHODS:
      A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6
      months. In group I (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100
      mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/
      3.8 years) 3TC was started 2 months prior to IFN-alpha2a. 3TC was continued for
      6 months after antiHBe seroconversion or stopped at 24 months in nonresponders.
      RESULTS: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/-
      45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV
      DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II,
      respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and
      II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and
      HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5%
      and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and II,
      respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough
      times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and
      none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05). Responders
      had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders.
      CONCLUSION: Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier
      antiHBe seroconversion and viral clearance than consecutive combined therapy.
      Relapse rate is low. Predictors of response are high basal ALT and high HAI
      scores. 3TC can be administered for 24 months without any side effect and
      breakthrough rate is comparable with previous studies.

PMID- 16640107
TI  - Neuropsychiatric adverse events after switching from an antiretroviral regimen
      containing efavirenz without tenofovir to an efavirenz regimen containing
      tenofovir: a report of nine cases.
AB  - The combination of tenofovir (TDF) and efavirenz (EFV) has not been associated
      with any pharmakokinetic interaction or with enhancement of neuropsychiatric
      disturbances. We report nine cases of neuropsychiatric intolerance occurring
      early after a switch from an antiretroviral regimen without TDF to an EFV and TDF
      containing regimen. Nine HIV-1-infected patients were treated with an EFV
      containing regimen for a median duration of 31 months without any EFV-related
      central nervous system (CNS) effects. They were switched to an EFV-TDF-containing
      regimen because of lipodystrophy (n=2) and/or the wish to simplify to a once
      daily regimen (n=9). Moderate to severe neuropsychiatric events occurred
      immediately (<48 hours) after TDF initiation in five patients and 2 weeks to 24
      months after the switch in the remaining four patients. Treatment modifications
      occurred in six patients (switch to EFV-nevirapine [n=3], TDF-zidovudine [n=2] or
      treatment discontinuation [n=1]), leading to a marked improvement of CNS
      intolerance. Treatment remained unchanged in three patients; two patients
      experienced chronic persistent sleeping disorders and one patient underwent a
      spontaneous improvement of symptoms within 2 weeks. EFV plasma concentrations,
      which were available in two patients before the switch and in four patients after
      the switch, remained in the therapeutic range. Although the exact mechanism of
      these symptoms remains hypothetical, neuropsychiatric disorders could be either a
      consequence of an unexplained interaction between EFV and TDF or an infrequent
      TDF-related side effect. The incidence of these side effects needs to be
      evaluated in large databases or pharmacokinetic studies.

PMID- 16640108
TI  - The American Association For the Study of Liver Diseases: new perspectives in the
      treatment of hepatitis C.

PMID- 16640109
TI  - Are cross-species measures of sensorimotor gating useful for the discovery of
      procognitive cotreatments for schizophrenia?
AB  - Prepulse inhibition of startle (PPI), a measure of sensorimotor gating used to
      identify antipsychotics, is reduced in schizophrenia patients and in rodents
      treated with dopamine agonists or glutamate antagonists. The National Institute
      of Mental Health (NIMH)-funded Measurement And Treatment Research to Improve
      Cognition in Schizophrenia (MATRICS) program has initiated a new era in the
      development of procognitive cotreatments in schizophrenia, independently of
      treating positive symptoms. Although PPI is not a cognitive process per se, such
      abnormalities in attention may be predictive of or lead to cognitive deficits.
      Since first-generation antipsychotics block PPI deficits induced by dopamine
      agonists, this model cannot identify cognitive enhancers for use as cotreatments
      with antipsychotics. PPI deficits caused by glutamate antagonists, like the
      exacerbation of symptoms they produce in patients, are insensitive to dopamine
      antagonists, but reduced by clozapine. Similarly, both PPI and cognitive deficits
      in schizophrenia patients are insensitive to first-generation antipsychotics, but
      attenuated by clozapine. Hence, treatment-induced reversals of glutamate
      antagonist effects on PPI may provide animal and human models to identify
      treatments of cognitive deficits in patients already treated with existing
      antipsychotics.

PMID- 16640110
TI  - Psychosis related to neurological conditions: pro and cons of the dis- / mis
      connectivity models of schizophrenia.
AB  - Schizophrenia is still a condition with obscure causes and psychopathology. This
      paper aims to discuss the "disconnectivity" hypothesis in relation to some
      neurological conditions which are known to alter brain connectivity, as well as
      mimicking some aspects of the disorder. After a short historical introduction to
      the concept, we will examine the evidence for connectivity problems in
      schizophrenia, separating the anatomical level from the functional level. Then,
      we will discuss three different issues concerning connectivity: i) local
      reduction in connectivity without neuronal loss (within the gray matter); ii)
      reduction in or alteration of long-range connectivity (within the white matter);
      and iii) abnormal targets for connections. For each of these aspects, we will
      look at the conditions able to reproduce anomalies capable of increasing
      susceptibility to schizophrenia. We conclude that psychosis is more likely to
      occur: i) when long-range connectivity is concerned; ii) when lesions result in
      lengthening and scattering of conduction times; and iii) when there are high
      dopamine levels, shedding light on or adding weight to the idea of an interaction
      between dopamine and connectivity.

PMID- 16640111
TI  - ADHD in adolescence and adulthood, with a special focus on the dopamine
      transporter and nicotine.
AB  - The persistence of attention deficit hyperactivity disorder (ADHD) into
      adolescence and adulthood has now been accepted as a clinical entity. The rate of
      prevalence among adults is assumed to be from 2% to 4%. With increasing age, a
      symptom change has to be considered; disturbance of attention becomes more
      prominent, whereas hyperactivity often diminishes or changes to inactivity.
      Neuroimaging studies show a high striatal dopamine transporter (DAT) availability
      in most adults with ADHD; this can be reduced by stimulants. Nicotine seems to
      have a stimulant-like action on the DAT. In most adults with ADHD, therapy has to
      be multimodal, combining psychotherapy and medication. Methylphenidate is the
      first-line drug in adult ADHD; further options are amphetamine and noradrenaline
      reuptake inhibitors. Nonresponders to methylphenidate seem to have no elevated
      DAT availability prior to therapy. Combination with other psychiatric disorders
      occurs frequently in adults with ADHD; in these patients additional
      pharmacological treatment with special regard to the comorbid disease is
      recommended.

PMID- 16640112
TI  - Substance abuse in patients with schizophrenia.
AB  - The comorbidity of schizophrenia and substance abuse has attracted increasing
      attention in the past years, with multiple potential links, including genetic
      vulnerability, neurobiological aspects, side effects of medications, and
      psychosocial factors being under discussion. The link between the use of
      substances and the development of psychoses is demonstrated by the high
      prevalence of substance abuse in schizophrenia. Apart from alcohol misuse,
      substances commonly abused in this patient group include nicotine, cocaine, and
      cannabis. In particular, heavy cannabis abuse has been reported to be a stressor
      eliciting relapse in schizophrenic patients. In general, substance use in
      psychosis is associated with poorer outcomes, including increased psychotic
      symptoms and poorer treatment compliance. Since both disorders have been observed
      to be closely interdependent, a particular treatment for schizophrenic patients
      with comorbidity of substance abuse is needed in order to provide more effective
      care. In this article, we discuss various potential modes of interaction and
      interdependence, and the possibility of embarking on new therapeutic paths for
      treating this particular population.

PMID- 16640113
TI  - Schizophrenia in late life: emerging issues.
AB  - Schizophrenia in late life is emerging as a major public health concern
      worldwide. We discuss several areas of research and clinical care that are
      particularly pertinent to older persons with schizophrenia, including the public
      health challenge and the cost of care. We then discuss clinical issues relevant
      to late-life schizophrenia (course of illness and cognition), medical care and
      comorbidity in older psychiatric patients (general and illness-related), and
      treatment concerns related to the use of atypical antipsychotics in older persons
      with psychosis (efficacy and side effects). Clinical care for this ever
      increasing segment of our population requires special consideration of the unique
      characteristics of older persons with schizophrenia.

PMID- 16640114
TI  - Effects of disorganization on choice reaction time and visual orientation in
      untreated schizophrenics.
AB  - Several preattentive mechanisms have proved to be sensitive markers of clinical
      change in schizophrenia. Two related studies of visuospatial orientation used
      cued target detection combined with choice reaction time, short/long preparation,
      with or without a signal/target interval ("gap"/ "no-gap," to detect attentional
      disengagement difficulty in schizophrenia). End points were reaction times,
      alertness scores, attentional cost/benefit, and validity scores. Study 1, in 13
      schizophrenics receiving second-generation antipsychotics and 13 controls, found
      the same impairment of disengagement as with neuroleptics, but intact reaction
      times and processing speed, with no hemispheric asymmetry. Study 2, in 12
      untreated acute schizophrenics and 12 controls, showed slower reaction times,
      near-zero alertness in the fixation release condition, and impaired valid/invalid
      discrimination versus Syndrome Scale disorganization subscore (r = -0.81; P <
      0.01). Early deficits in the preattentive orientation and visual. Early deficits
      in the preattentive orientation and visual detection phases are useful for
      assessing response to psychotropic treatment and establishing clinical correlates
      in acute schizophrenia.

PMID- 16640115
TI  - A review of emotion deficits in schizophrenia.
AB  - Emotion deficits in schizophrenia have been described since the time of
      Kraepelin. However, no comprehensive review of clinical emotion studies has ever
      been conducted. In this work, studies that used diagnostic criteria and were
      published in English were selected from an extensive PubMed search. Fifty-five
      studies on emotion expression repeatedly showed that individuals with
      schizophrenia (IWSs) display fewer overt expressions than nonpatient comparison
      subjects (NCSs) in verbal, facial, and acoustic channels. No clear differences
      were found between IWSs and depressed subjects. Sixty-nine studies examined
      emotion experience in schizophrenia. IWSs report higher anhedonia, and they tend
      to show more negative emotions in real-life event studies. In evocative studies,
      they report a similar degree of pleasantness and a similar or higher degree of
      unpleasantness. From 110 studies, it can be concluded that emotion recognition is
      impaired in schizophrenia in all channels. These deficits in social perception
      are correlated with neurocognitive deficits and some social skills. IWSs show
      dysfunction in the three domains of emotion expression, emotion experience, and
      emotion recognition, and these dysfunctions appear to be independent of each
      other across domains. These deficits in basic emotion processing may be linked to
      psychopathology and functional outcomes.

PMID- 16640116
TI  - Understanding structural brain changes in schizophrenia.
AB  - Schizophrenia is a chronic progressive disorder that has at its origin structural
      brain changes in both white and gray matter. It is likely that these changes
      begin prior to the onset of clinical symptoms in cortical regions, particularly
      those concerned with language processing. Later, they can be detected by
      progressive ventricular enlargement. Current magnetic resonance imaging (MRI)
      technology can provide a valuable tool for detecting early changes in cortical
      atrophy and anomalous language processing, which may be predictive of who will
      develop schizophrenia.

PMID- 16640117
TI  - Clinical impact of recently detected susceptibility genes for schizophrenia.
AB  - After years of frustration, the search for genes impacting on schizophrenia is
      now undergoing some exciting developments. Several proposals of susceptibility
      genes have been able to be supported by replications. Thus, there are now at
      least three very strong candidates: the gene for dysbindin (DTNBP1), the gene for
      neuregulin-1 (NRG1), and a less well-understood gene locus, G72/G30, which are
      likely to influence manifestations of schizophrenia. Other "hot" candidates such
      as the disrupted-in-schizophrenia 1 gene (DISC1) and the gene coding for protein
      kinase B (AKT1) might also prove to be susceptibility genes in the next future.
      The clinical implications of these findings are not yet fully visible. However,
      some first insights are possible: most of the genetic findings lack diagnostic
      specificity, and are also reproduced in bipolar disorder. Strong associations are
      also obtained on a symptomatic level, not only on a diagnostic level. The
      pathophysiological role of these hot candidate genes is currently under intensive
      study.

PMID- 16640118
TI  - Pharmacogenetics of antipsychotic therapy: pivotal research issues and the
      prospects for clinical implementation.
AB  - The core hypothesis underlying pharmacogenetics is that genetic factors play a
      significant role in the well-recognized differences between individuals in
      response to medication and susceptibility to adverse effects. If these genetic
      factors can be identified and understood, they may serve as predictors to guide
      clinicians in tailoring medication to the individual patient. Recent developments
      in the field of antipsychotic drug treatment suggest that pharmacogenetics could
      play an important role, permitting the use of first-generation antipsychotics
      (FGAs) for patients in whom the use of second-generation antipsychotics (SGAs) is
      limited by efficacy considerations or adverse effects. In this paper, key issues
      that need to be taken into consideration in designing and interpreting
      pharmacogenetic studies of antipsychotic drugs are discussed against the
      background of data emanating from studies on the genetics of tardive dyskinesia
      (TD), an important adverse effect of FGAs. The issues considered include the
      advantages and potential pitfalls of case-control association studies of
      pharmacogenetic traits, the role of demographic factors such as age and gender,
      additive effects of genes, and gene-gene and gene-environment interaction. The
      prospects for implementation of pharmacogenetic testing in the clinic are
      considered in the context of a preliminary model that has been tested for
      prediction of susceptibility to TD.

PMID- 16640120
TI  - The development concept of "endogenous psychoses".
AB  - Several structural deviances in the brain in "endogenous psychoses" have been
      described over the last decades. The enlargement of the lateral ventricles and
      the subtle structural deficits in temporobasal and orbital frontal structures
      (hypofrontality) are reasonably well established in the majority of schizophrenic
      patients. We examined the cytoarchitecture of these important central structures,
      namely the entorhinal region and the orbitofrontal cortex (Brodmann area 11),
      which have been under meticulous investigation in our laboratories over the last
      few decades. In a new series of schizophrenic patients and normal controls, we
      made serial cuts of the whole rostral entorhinal cortex on both sides. For this
      report, we selected two cases with very different psychopathologies, and present
      the serial cuts through both hemispheres and the malformations found. We report
      on the differing magnitude of the heterotopic malformations (for definition see
      page 103), either bilaterally or unilaterally.

PMID- 16640119
TI  - Dopaminergic intracellular signal integrating proteins: relevance to
      schizophrenia.
AB  - Changes in dopaminergic function can be regulated by receptor-receptor
      interaction, or interaction with other proteins with dopamine receptors, and/or
      elements of the downstream signaling cascades. The complexity of dopaminergic
      signaling is far from being completely elucidated. It could, however, hold the
      key to the comprehension of the pathophysiology of neurological and psychiatric
      disorders, as well as to the identification of putative new targets for, and
      development of, more efficacious and selective drugs. Here, we review some of the
      current evidence and new ideas that are being proposed as a result, as well as
      future perspectives that are now being recognized.

PMID- 16640121
TI  - The NIMH-MATRICS project for developing cognition-enhancing agents for
      schizophrenia.
AB  - The US National Institute of Mental Health supported an initiative to facilitate
      the development of pharmacological agents for enhancing neurocognition in
      patients with schizophrenia. This has been accomplished through a consensus
      building process that has included representatives from academia, the
      pharmaceutical industry, and government. The group has addressed obstacles to
      drug development that include (i) the lack of a well-accepted instrument for
      measuring neurocognition in clinical trials; (ii) the lack of a consensus on the
      best molecular target or targets for drug development; (iii) the lack of a
      consensus regarding the optimal trial design for either comedication that
      improves cognition when added to an antipsychotic or a broad spectrum agent that
      improves cognition and treats psychosis; and (iv) the approaches of regulatory
      agencies such as the US Food and Drug Administration to approving and labeling a
      new agent.

PMID- 16640122
TI  - The German Research Network on Schizophrenia--impact on the management of
      schizophrenia.
AB  - The German Research Network On Schizophrenia (GRNS) is a nationwide network
      currently comprising 16 psychiatric university departments and 14 state and
      district hospitals, as well as six local networks of psychiatric practices and
      general practitioners collaborating on about 25 interrelated, multicenter
      projects on schizophrenia research. The GRNS aims to intensify collaboration and
      knowledge exchange between leading research institutions and qualified routine
      care facilities, both within (horizontal network) and between (vertical network)
      the two levels of research and care, in order to create the scientific
      preconditions for optimization of the management of schizophrenia. The concept
      and the first results of studies aiming at the investigation of (i) strategies
      for early detection and early intervention in the prodromal stage of psychosis;
      (ii) treatment in first-episode schizophrenia; (iii) quality management; and (iv)
      destigmatization, are described as examples of this effort.

PMID- 16640123
TI  - Quantitative analysis of motor disturbances in schizophrenic patients.
AB  - The presence of neurological signs and disturbed psychomotor performance have
      been consistently confirmed by clinical studies in schizophrenic patients. These
      parameters are mainly assessed by using clinical rating scales. In recent years,
      new approaches such as ultrasonic movement analysis systems have been introduced
      in order to objectively evaluate motor disturbances in schizophrenic patients.
      Ultrasonic movement analysis systems calculate the three-dimensional positions of
      tiny markers, which are attached to moving body parts, with high spatial and
      temporal resolution. Thus, key parameters of gait and hand movements can be
      determined precisely. This article summarizes and discusses several studies using
      these new methods. Results indicate that schizophrenia causes a specific motor
      deficit pattern, with a predominant disturbance of spatial parameters.
      Conventional antipsychotic treatment usually worsens these deficits, whereas the
      effects of atypical antipsychotic treatments are less pronounced. Disturbed motor
      performance can be normalized by external sensory stimuli, but only when no major
      attentional processes are required, and it can be enhanced by an attentional
      strategy, but not to the extent that motor parameters are normalized.

PMID- 16640124
TI  - The impact of subjective well-being under neuroleptic treatment on compliance and
      remission.
AB  - The patients' perspective of antipsychotic treatment was largely neglected for a
      long period. It has only been during the last 10 years, with the development of
      atypical antipsychotics, that scientific interest in this issue has markedly
      increased. Numerous studies have shown that the majority of schizophrenic
      patients are able to fill out a self-rating scale in a meaningful way, and
      several self-report scales with sufficient internal consistency and good
      construct validity have been developed. The effects of antipsychotic treatment on
      psychopathology and on subjective well-being (SW) are not strongly related; the
      perspectives of the patient and his/her psychiatrist markedly differ. Recent
      research indicates that SW/quality of life, much more improved by atypical than
      by typical antipsychotics, has a strong impact on compliance, as well as on the
      chance of achieving remission. The data strongly suggest that a systematic
      evaluation of the patient's perspective of antipsychotic treatment is meaningful
      and necessary to increase compliance, functional outcome, and long-term
      prognosis.

PMID- 16640125
TI  - A dopaminergic deficit hypothesis of schizophrenia: the path to discovery.
AB  - In contrast to the conventional view of dopamine involvement in schizophrenia,
      which posits hyperactive dopaminergic transmission, we propose that for unknown
      developmental and/or biochemical reasons, a primary defect occurs in efficient,
      tight dopaminergic synaptic transmission, triggering feedback activation and
      receptor upregulation, and resulting in the well-characterized increase in
      dopaminergic tone. This hypothesis is driven by suggestive evidence for
      subpopulations of dopamine D2 receptors delivering contrasting forms of
      dopaminergic transmission: synaptic receptors, responsible for basic dopaminergic
      function and subject to effective feedback control, and poorly controlled
      extrasynaptic receptors partly responsible for the positive symptoms of
      psychosis. Since the primary defect is dopamine deficiency, we term this theory
      the dopaminergic deficit hypothesis of schizophrenia. It is currently informing
      clinical studies with novel partial dopamine antagonists (dopamine stabilizers)
      such as ACR16, which preferentially target extrasynaptic receptors while leaving
      synaptic transmission and basic dopamine function intact.

PMID- 16640126
TI  - Helping Canadians understand the opportunities for health research.

PMID- 16640127
TI  - Translating a broad term into real-world applications: CIHR's successful approach
      to knowledge translation.

PMID- 16640128
TI  - CIHI survey. Alternatives to acute care?

PMID- 16640129
TI  - Quality of care and outcomes of older heart failure patients: is the United
      States doing a better job than Canada?

PMID- 16640130
TI  - A dialogue on quality and patient safety with Maureen Bisognano. Interview by G.
      Ross Baker.

PMID- 16640131
TI  - Experiences of regionalization: assessing multiple stakeholder perspectives
      across time.
AB  - This paper constructs a beginning frame for analyzing experiences of
      regionalizing in healthcare systems. Using Alberta as a case example, it traces
      the perspectives of multiple stakeholders (government, RHAs, frontline staff and
      public) on key organizational dimensions to describe the various experiences of
      organizing healthcare through regionalization. As a team of organizational and
      health researchers, we have been studying this case together and separately for
      10 years. We present the framing and our case example to encourage future
      discussions, debates and consideration of this structural arrangement for
      healthcare that has swept across most of Canada. We believe that it is critical
      to learn more about both the pitfalls and potentials that regionalization
      produces across time and through change for the delivery of care and the
      protection and improvement of health. And we believe that perspective matters
      when assessing the full impacts of regionalizing and re-regionalizing and the
      multiple change processes embedded within these large structural
      reconfigurations.

PMID- 16640132
TI  - Ontario's wait time strategy: part 1.
AB  - Ontario's Wait Time Strategy was designed to improve access to healthcare
      services in the public system by reducing the time that adult Ontarians wait for
      services in five areas-cancer surgery, cardiac revascularization procedures
      (cardiac surgery, percutaneous coronary intervention, diagnostic
      catheterization), cataract surgery, hip and knee total joint replacements and MRI
      and CT scans. These five are just the beginning of an ongoing process to improve
      access to, and reduce wait times for, a broad range of healthcare services.

PMID- 16640133
TI  - CCHSA Client/Patient Safety Culture Assessment Project: lessons learned.
AB  - Implemented in Spring 2005, the objective of CCHSA's client/patient safety
      culture assessment project was to help organizations measure attitudes toward
      safety culture and to provide insights into areas that are already strong as well
      as areas that require improvement. The assessment also encouraged health service
      organizations to think strategically about client/patient safety culture.

PMID- 16640134
TI  - A statistical survey of Canadian forensic mental health inpatient programs.
AB  - Secure hospital beds are vitally important for the assessment and treatment of
      mentally disordered accused persons. A forensic mental health system with an
      adequate level of hospital beds is essential for the courts and review boards to
      carry out of the mental disorder provisions of the Criminal Code. This article
      describes the results of a study that examined interprovincial differences in the
      structure of Canadian forensic mental health FMH inpatient programs. In total,
      1523 hospital beds are designated for FMH programs in Canada. Across Canada, less
      than one (0.61) FMH hospital bed is available for every 10,000 adults in the
      general population, ranging from 0.37 in Manitoba to 1.08 in Nova Scotia.
      Interprovincial differences in the staffing and bed occupancy of Canadian FMH
      inpatient programs are also uncovered. The results of the present study confirm
      that interprovincial differences in the structure and organization of FMH
      inpatient programs exist in Canada.

PMID- 16640135
TI  - The effect of a primary care intervention on management of patients with diabetes
      and hypertension: a pre-post intervention chart audit.
AB  - BACKGROUND: A principal goal in enhancing primary care in Canada is to increase
      emphasis on health promotion, disease prevention and the management of chronic
      diseases in the primary care setting. To achieve this goal in Nova Scotia,
      collaborative practice teams with a nurse practitioner and at least one physician
      were established, and both alternative funding arrangements for physicians and an
      information system were implemented. This study reports on the impact of this
      primary healthcare reform initiative on the quality of process-of-care, self-care
      and proxy measures for specific health outcomes for patients with diabetes and
      hypertension. METHODS: A pre- (April 1, 1999-March 31, 2000) post- (April 1, 2001
      March 31, 2002) intervention audit of consenting patients was conducted at the
      four sites participating in the Strengthening Primary Care Initiative. Two
      hundred and eleven charts of patients with diabetes and 541 charts of patients
      with hypertension were audited. Process-of-care, targeted health outcomes,
      patient education and self-care items were measured for patients with diabetes.
      Process-of-care and outcome measures related to clinical management, blood
      pressure, lifestyle modifications and laboratory investigations were measured for
      patients with hypertension. Frequencies and proportions were calculated.
      McNemar's test was used to compare paired data pre- and postintervention.
      RESULTS: The percentage of patients with diabetes who achieved target blood
      pressure control rose from 20.4 to 28.5%. Annual screening for retinopathy
      increased from 33.8 to 41.9% and nephropathy from 61.7 to 71.3%. The percentage
      of patients monitoring blood glucose levels at home increased from 61.5% to
      69.1%. HYPERTENSION: The percentage of patients with hypertension who had their
      blood pressure checked at least twice a year dropped from 89.1% to 85.0%;
      however, more patients achieved target systolic (rising from 40.6 to 55.3%) and
      diastolic (from 77.9 to 85.3%) blood pressure readings. Body mass index was
      recorded and moderate exercise prescribed to more patients. The percentage of
      patients with recorded fasting blood glucose levels (from 37.7 to 67.1%) and
      lipid profiles (from 62.6 to 69.1%) was markedly higher. CONCLUSION: Overall
      patient care related to diabetes and hypertension was either maintained or
      improved over the course of the initiative.

PMID- 16640136
TI  - Collaborative partnerships: managing increased healthcare demand without
      increasing overall system capacity.
AB  - Collaborative partnerships can help improve integration and quality in local
      healthcare systems. We describe an innovative approach that was implemented
      following the formation of a tri-provider partnership between homecare and two
      acute care hospitals. The approach questioned the prevailing thought that the
      home is always the most appropriate and least costly location to provide services
      to clients traditionally served by homecare. The goal was to improve the delivery
      of healthcare by better integrating patient characteristics with services
      provided by homecare, hospitals and family physicians. The result was the
      implementation of a pilot project in which both homecare clients and non-urgent
      hospital patients could be served in a hospital-based ambulatory nursing care
      clinic.

PMID- 16640137
TI  - Reinventing Veterans Health Administration: focus on primary care.
AB  - Can we improve access in primary care without compromising the quality of care?
      The purpose of this article is to demonstrate how timely access to primary care
      can be achieved without compromising the quality of the care being delivered.

PMID- 16640138
TI  - A collaborative approach to building capacity in health informatics.

PMID- 16640139
TI  - Bridging information "islands": designing an electronic health record that meets
      clinical needs.

PMID- 16640140
TI  - Clinical portals: a win for providers.

PMID- 16640141
TI  - The Ottawa Hospital celebrates green success.

PMID- 16640142
TI  - Networks share, access and store digital medical images: the Thames Valley
      initiative.

PMID- 16640143
TI  - Public health detailing: a strategy to improve the delivery of clinical
      preventive services in New York City.
AB  - To promote use of essential clinical preventive services, the New York City
      Department of Health and Mental Hygiene developed the Public Health Detailing
      Program, a primary care provider outreach initiative modeled on pharmaceutical
      detailing. Department representatives conducted topical campaigns, making
      unscheduled visits to health care practices and meeting with providers and office
      staff members. Representatives distributed "action kits" containing practice
      tools, provider information, and patient education materials; nicotine
      replacement therapy was distributed during the smoking cessation campaign. More
      than 2,500 interactions with practice staff members were completed by six health
      department representatives at approximately 200 sites. Physician visits lasted 10
      minutes or longer, and by provider self-report, use of office systems for
      prevention and adherence to recommended practices increased. Public health
      detailing is an effective method of reaching providers to deliver key prevention
      messages, feasible for public health agencies and acceptable to practices. The
      effectiveness of this intervention in improving clinical prevention services
      requires further evaluation.

PMID- 16640144
TI  - Settlement-funded tobacco control in Texas: 2000-2004 pilot project effects on
      cigarette smoking.
AB  - Because settlement proceeds allocated for tobacco control in Texas are
      insufficient for statewide activity at federally recommended funding levels, the
      Texas Department of State Health Services has used the available funds in quasi
      experimental pilot studies in which varying amounts of support are provided for
      selected parts of the state. Trends in tobacco use were measured in telephone
      surveys of 7,998 (2000), 5,150 (2002), and 5,721 (2004) adults. Prevalence of
      cigarette smoking declined by almost one-third in the pilot area where
      comprehensive and sustained pilot activities to reduce tobacco use were organized
      at close to the federally recommended funding level. Significantly smaller
      reductions were observed in other parts of the state. In the group with the
      highest use, white non-Hispanic men, cigarette consumption declined by half in
      the pilot area. It is reasonable to expect similar reductions in tobacco use if
      funds are provided for statewide expansion of the pilot activities.

PMID- 16640145
TI  - The association of low birthweight and chronic renal failure among Medicaid young
      adults with diabetes and/or hypertension.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of low birthweight
      on chronic renal failure among young Medicaid patients with diabetes and/or
      hypertension. METHODS: The study included Caucasian and African American young
      adults, aged 18-50, who enrolled in the Medicaid program from 1993 to 1996 in
      South Carolina and were diagnosed with diabetes and/or hypertension. The odds of
      chronic renal failure by low birthweight (< 2,500 grams) was estimated using
      logistic regression. RESULTS: Of the 7,505 Medicaid patients with diabetes and/or
      hypertension, 179 (2.4%) were diagnosed with chronic renal failure. These
      patients were younger (mean age of 33.9 vs. 37.6, p = 0.0024) and had a higher
      proportion of low birthweight (15.1% vs. 11.4%, p = 0.07) compared with the 7,326
      patients without renal failure. The odds ratio of chronic renal failure for low
      birthweight was significantly higher compared with normal birthweight (2,500
      3,999 grams) (adjusted odds ratio [OR] 1.56, 95% confidence interval [95% CI]
      1.0, 2.4). The association between low birthweight and chronic renal failure was
      stronger among the 888 patients with both diabetes and hypertension (OR 2.6, 95%
      Cl 1.3, 5.7) than the 1,812 diabetes or the 4,805 hypertension patients.
      CONCLUSIONS: The odds of chronic renal failure by low birthweight was highest in
      patients with both diabetes and hypertension, suggesting that the mechanism(s)
      involved in the disease progression to chronic renal failure may have a fetal
      early life origin.

PMID- 16640146
TI  - Does literacy mediate the relationship between education and health outcomes? A
      study of a low-income population with diabetes.
AB  - OBJECTIVES: We sought to determine whether literacy mediates the relationship
      between education and glycemic control among diabetes patients. METHODS: We
      measured educational attainment, literacy using the Short Test of Functional
      Health Literacy in Adults (s-TOFHLA), and glycemic control (HbA1c) in 395
      diabetes patients at a U.S. public hospital. We performed path analysis to
      compare two competing models to explain glycemic control. The direct effects
      model estimated how education was related to HbA1c; the mediational model
      estimated the strength of the direct relationship when the additional pathway
      from education to literacy to HbA1c was added. RESULTS: Both the model with a
      direct effect of education on HbA1c and the model with literacy as a mediator
      were supported by good fit to observed data. The mediational model, however, was
      a significant improvement, with the additional path from literacy to HbA1c
      reducing the discrepancy from observed data (p < 0.01). After including this
      path, the direct relationship between education and HbA1c fell to a non
      significant threshold. CONCLUSIONS: In a low-income population with diabetes,
      literacy mediated the relationship between education and glycemic control. This
      finding has important implications for both education and health policy.

PMID- 16640147
TI  - Alleged B. anthracis exposure claims in a workers' compensation setting.
AB  - OBJECTIVES: Workers' compensation insurance in some states may not provide
      coverage for medical evaluation costs of workplace exposures related to potential
      bioterrorism acts if there is no diagnosed illness or disease. Personal insurance
      also may not provide coverage for these exposures occurring at the workplace.
      Governmental entities, insurers, and employers need to consider how to address
      such situations and the associated costs. The objective of this study was to
      examine characteristics of workers and total costs associated with workers'
      compensation claims alleging potential exposure to the bioterrorism organism B.
      anthracis. METHODS: We examined 192 claims referred for review to the Ohio Bureau
      of Workers' Compensation (OBWC) from October 10, 2001, through December 20, 2004.
      RESULTS: Although some cases came from out-of-state areas where B. anthracis
      exposure was known to exist, no Ohio claim was associated with true B. anthracis
      exposure or B. anthracis-related illness. Of the 155 eligible claims, 126
      included medical costs averaging dollar 219 and ranging from dollar 24 to dollar
      3,126. There was no difference in mean cost for government and non-government
      employees (p = 0.202 Wilcoxon). CONCLUSIONS: The number of claims and associated
      medical costs for evaluation and treatment of potential workplace exposure to B.
      anthracis were relatively small. These results can be attributed to several
      factors, including no documented B. anthracis exposures and disease in Ohio and
      prompt transmission of recommended diagnostic and prophylactic treatment
      protocols to physicians. How employers, insurers, and jurisdictions address
      payment for evaluation and treatment of potential or documented exposures
      resulting from a potential terrorism-related event should be addressed
      proactively.

PMID- 16640148
TI  - Measles immunization coverage determined by serology and immunization record from
      children in two Chicago communities.
AB  - OBJECTIVES: We compared the prevalence of measles immunization determined by
      serology with the prevalence of measles immunization determined by immunization
      records, and identified factors predictive of measles immunization among a sample
      of children from two Chicago communities. METHODS: We collected demographic
      information and blood specimens from a sample of children aged 12-71 months in
      two Chicago communities at risk for low measles immunization coverage levels. We
      collected immunization information from provider records, parent-held records,
      and the statewide immunization registry. We compared evidence of immunization
      determined by serology with evidence of immunization from these three sources of
      immunization records. RESULTS: The sample of children from the two communities
      had serologic measles immunity levels of 85% and 90%. Significantly fewer
      children had evidence of immunization by record in both communities (45% and 63%,
      respectively). CONCLUSIONS: Immunization coverage levels determined using
      immunization records were significantly lower than immunization coverage
      determined using serology. A fully populated immunization registry used by all
      immunization providers could prevent the problems of record loss and scatter.

PMID- 16640149
TI  - The role of flushing dental water lines for the removal of microbial
      contaminants.
AB  - OBJECTIVES: This study was designed to determine the role of flushing dental
      water lines for the removal of heterotrophic plate count bacteria, Legionella
      spp., and free-living protozoa. METHODS: Forty dental offices were surveyed in
      the study. An initial sample and a sample taken after three minutes of flushing
      were obtained from the air/water syringe at each location. All samples were
      quantitatively analyzed for heterotrophic bacteria using three bacteriological
      procedures. The samples were analyzed for the presence of Legionella spp. using
      cultural, immunological, and molecular procedures and for the occurrence of free
      living protozoa using a killed bacteria plate procedure. RESULTS: The flushing
      process reduced the level of heterotrophic plate count bacteria by 1.1 to 1.5
      log10 CFU/ml. Compliance with recommendations for bacterial levels varied
      depending on the methodology employed in the analysis. The flushing process did
      not reduce the occurrence of Legionella spp. or free-living protozoa. CONCLUSION:
      The results support recent U.S. Centers for Disease Control and Prevention
      recommendations that the process of flushing dental water lines cannot be relied
      upon as a sole means of reliably improving the quality of water used in dental
      treatment.

PMID- 16640150
TI  - Use of death certificates to study ethnic-specific mortality.
AB  - OBJECTIVES: The Hispanic population in the United States represents more than 40
      million individuals, with Mexican Americans (MA) as the largest subgroup. To
      assess the utility of death certificates and medical records as the source of
      race/ethnicity data for epidemiologic studies, we compared self-reported race/
      ethnicity to race/ethnicity recorded on death certificates and medical records in
      a bi-ethnic, non-immigrant U.S. community with a significant MA population.
      METHODS: This study utilized data collected from a subset of 1,856 participants
      of the Brain Attack Surveillance in Corpus Christi (BASIC) project. In-person
      interviews were conducted to determine self-reported race/ethnicity. Of those
      interviewed, 480 subsequently expired. Using self-reported race/ethnicity as the
      gold standard, we determined percent agreement, sensitivity, and specificity of
      the death certificate and medical record. RESULTS: Of the 480 subjects, 259 self
      reported their race/ethnicity as non-Hispanic white (NHW), 195 self-reported as
      MA, and 26 self-reported as non-Hispanic black. Median age was 78.5 years and
      55.8% were female. Percent agreement between self-reported race/ethnicity and
      race/ethnicity recorded on the death certificate and medical record was 97.1% and
      96.3% respectively. Five percent of MAs were misclassified as NHW on their death
      certificates and 3% on their medical records. CONCLUSIONS: Results indicated that
      Hispanic designation recorded on death certificates and medical records in this
      community was largely consistent with that of self-report. This study suggests
      that vital statistics data in non-immigrant U.S. Hispanic communities can be used
      with confidence to investigate ethnic-specific aspects of disease and mortality.
      Similar studies in other multi-racial communities should be conducted to confirm
      and generalize these results.

PMID- 16640151
TI  - Evaluation of death certificate-based surveillance for traumatic brain injury-
      Oklahoma 2002.
AB  - OBJECTIVES: Death certificate data are used to estimate state and national
      incidence of traumatic brain injury (TBI)-related deaths. This study evaluated
      the accuracy of this estimate in Oklahoma and examined the case characteristics
      of those persons who experienced a TBI-related death but whose death certificate
      did not reflect a TBI. METHODS: Data from Oklahoma's vital statistics multiple
      cause-of-death database and from the Oklahoma Injury Surveillance System database
      were analyzed for TBI deaths that occurred during 2002. Cases were defined using
      the Centers for Disease Control and Prevention (CDC) ICD-10 code case definition.
      In multivariate analysis using a logistic regression model, we examined the
      association of case characteristics and the absence of a death certificate for
      persons who experienced a TBI-related death. RESULTS: Overall, sensitivity of
      death certificate-based surveillance was 78%. The majority (62%) of missed cases
      were due to listing "multiple trauma" as the cause of death. Death certificate
      surveillance was more likely to miss TBI-related deaths among traffic crashes,
      falls, and persons aged > or = 65 years. After adding missed cases to cases
      captured by death certificate surveillance, traffic crashes surpassed firearm
      fatalities as the leading external cause of TBI-related death. CONCLUSIONS: Death
      certificate surveillance underestimated TBI-related death in Oklahoma and might
      lead to national underreporting. More accurate and detailed completion of death
      certificates would result in better estimates of the burden of TBI-related death.
      Educational efforts to improve death certificate completion could substantially
      increase the accuracy of mortality statistics.

PMID- 16640152
TI  - Putting "child mental health" into public health.

PMID- 16640153
TI  - Mental health in schools and public health.

PMID- 16640154
TI  - Improving the care of children with mental illness: a challenge for public health
      and the federal government.

PMID- 16640155
TI  - Estimating the prevalence of early childhood serious emotional/behavioral
      disorders: challenges and recommendations.

PMID- 16640156
TI  - Children's health services in a "system of care": patterns of mental health,
      primary and specialty use.
AB  - OBJECTIVES: This study was designed to investigate demonstrable impacts of the
      Mental Health Services Program for Youth (MHSPY), a highly coordinated,
      intentionally integrated "system of care," on patterns of health service
      utilization for youth with multiple needs. METHODS: The MHSPY intervention is
      available to a target population of urban youth who face barriers to health care
      and are at risk for out-of-home placement. These youth are enrolled in a non
      profit managed care organization (MCO). Patterns of medical, pharmacy, and mental
      health and substance abuse service use were compared for children aged 3 to 19
      across insurance categories. RESULTS: Despite risks for access and engagement
      barriers to care, and for greater medical expense due to greater morbidity, MHSPY
      enrollees received significantly more ambulatory care per person-year than either
      the privately insured population or the Medicaid Standard population, and medical
      expense for MHSPY members was significantly lower than expected. During the four
      years studied, individuals in the privately insured and Medicaid Standard
      populations were less likely than MHSPY enrollees to have had an ambulatory
      pediatric visit (odds ratio [OR] 0.833, 95% confidence interval [CI] 0.765, 0.908
      and OR 0.823, 95% CI 0.775, 0.897, respectively). Medical expenses per member per
      month for MHSPY enrollees were significantly less than that for the similarly
      impaired Medicaid Disabled population with any medical claim (p < 0.001) or with
      any outpatient mental health claim (p < 0.01). CONCLUSIONS: Patterns of health
      care for subpopulations with known risk are important to identify to evaluate
      system-of-care effectiveness. The service utilization patterns for youth enrolled
      in the MHSYP system of care vs. those for similar MCO youth suggest health care
      access for individuals can be affected by delivery system design variables.

PMID- 16640157
TI  - The use of AAP-recommended disciplinary practice guidelines among African
      American caregivers of children in Head Start programs.
AB  - OBJECTIVE: The American Academy of Pediatrics (AAP) recommends that parents not
      use harsh disciplinary practices. Previous studies have characterized the
      disciplinary practices of African American parents as harsh, with reliance on
      more aggressive techniques not currently recommended by the AAP. However, recent
      research has indicated more disciplinary practice diversity among African
      Americans. This study describes factors associated with the use of AAP
      recommended disciplinary practices among lower-income African American caregivers
      of children in Head Start. METHODS: Subjects were caregivers of children at three
      Head Start sites. Participants were eligible for inclusion if the biological
      mother, biological father, or target child was identified as African American.
      Using consensus methods, responses to the Parental Discipline Methods Interview
      (PDMI) were described as consistent or inconsistent with AAP guidelines regarding
      use of negative disciplinary practices (e.g., spanking, yelling). Caregivers
      avoiding any of these inconsistent methods were referred to as "adherent."
      RESULTS: "Adherent" caregivers were older (32.5 years vs. 30.4 years) and had
      more education (86.0% vs. 75.4% high school graduates). They were also less
      likely to report that their child had behavioral problems (12.9% vs. 25.2%) or
      deficient social skills (1.7% vs. 8.0%). CONCLUSIONS: Lower-income African
      American caregivers were more likely to use disciplinary practices consistent
      with AAP guidelines if they had higher levels of education and were living in an
      urban setting. Caregivers describing their child as having fewer behavior
      problems, better social skills, or themselves as less stressed were also more
      likely to be "adherent."

PMID- 16640158
TI  - English language skills and diabetes and hypertension among foreign-born South
      Asian adults in England.

PMID- 16640159
TI  - Town of Castle Rock, Colorado v Gonzales: implications for public health policy
      and practice.

PMID- 16640160
TI  - Service learning to impact homelessness: the result of academic and community
      collaboration.

PMID- 16640161
TI  - Injury prevention and control research and training in accredited schools of
      public health: a CDC/ASPH assessment.

PMID- 16640162
TI  - An overview of public health in the new millenium: individual liberty vs. public
      safety.

PMID- 16640163
TI  - No value for a pound of flesh: extending market-inalienability of the human body.

PMID- 16640164
TI  - Pee-to-park: should public high school students applying for on-campus parking
      privileges be required to pass a drug test?

PMID- 16640165
TI  - The need for parity in health insurance benefits for the mentally and physically
      disabled: questioning inconsistency between two leading anti-discrimination laws.

PMID- 16640166
TI  - United States v. Sell: involuntary administration of antipsychotic medication.
      Are you dangerous or not?

PMID- 16640167
TI  - 2005 Speaker Series: Dr. Joseph Rohan Lex, Jr., M.D. FAAEM. The physician
      pharmaceutical industry relationship.

PMID- 16640168
TI  - Calcium channel blockers in hypertension. Is there still a controversy?
AB  - There are several reasons why no single antihypertensive drug class is ideal in
      all clinical situations. First, pathophysiologic heterogeneity in hypertension
      and diversity of mechanisms of antihypertensive drugs dictate that no single drug
      class can be optimally effective in all subpopulations. Second, sustained blood
      pressure control generally requires combination therapy to block the reflex
      stimulation of physiologic mechanisms that attempt to restore blood pressure to
      pretreatment levels. Third, while effective blood pressure control is more
      important than choice of initial drug in the prevention of hypertension-related
      morbidity and mortality, specific drug classes are indicated for optimal
      treatment of complications of hypertension (e.g. heart failure, kidney disease).
      Fourth, although antihypertensive drug side effects are uncommon, alternative
      strategies are required in some patients. Given these principles, past
      controversies regarding whether calcium channel blockers (CCBs) should be used in
      the treatment of hypertension become moot. CCBs are extremely effective in
      lowering blood pressure and in preventing stroke and cardiovascular disease. When
      additional blood pressure lowering is necessary to meet strict targets, CCBs may
      be added, even in heart failure or chronic kidney disease, where CCBs alone may
      not achieve optimal outcomes. Combinations of CCBs with "anti-neurohumoral" drugs
      such as ACE inhibitors are particularly useful to achieve sustained blood
      pressure control, reduce adverse effects such as edema, and improve outcomes.

PMID- 16640169
TI  - Calcium channel blockers and coronary heart disease.
AB  - Calcium channel blockers (CCBs) are drugs with several pharmacological
      properties, widely used in cardiovascular medicine for a variety of indications,
      including treatment of hypertension and angina pectoris. This review summarizes
      the most recent evidence on coronary outcomes of CCBs, used either to treat
      hypertension or in secondary prevention of overt coronary heart disease (CHD).
      The anti-atherosclerotic properties of these drugs will also be reviewed. Several
      randomized trials and meta-analyses published from the mid-1990s indicate that,
      as a class, CCBs are superior to placebos in preventing CHD events in patients
      with hypertension, although in head-to-head comparisons with other
      antihypertensive agents their effects are more controversial and largely
      dependent on the specific CCB considered. Conversely, older studies report that
      short-acting CCBs may increase the risk of CHD outcomes, a finding contradicted
      by recent trials on long-acting, lipophilic agents. In patients with prevalent
      CHD, CCBs do not improve survival and most major CHD outcomes, although they
      reduce symptoms of angina and the need for revascularization procedures also in
      active treatment comparisons. Besides their action on blood pressure and on
      coronary vessel smooth muscle, this protective effect is probably mediated by
      their plaque stabilization properties.

PMID- 16640170
TI  - Calcium channel blockers and stroke.
AB  - The most frequent indication for Calcium Channel Blockers (CCBs) is their use as
      antihypertensive agents for primary or secondary stroke prevention. Hypertension
      contributes to virtually all mechanisms of stroke, of atherothrombotic, lacunar,
      cardioembolic and intraparenchymal hemorrhage types. In comparison with the
      rather univocal mechanisms underlying coronary artery or peripheral artery
      disease, the variable mechanisms of stroke are the main reason explaining not
      only the different impact of vascular risk factors, but also the different
      effects of drugs given for prevention. In an acute stroke setting, lowering blood
      pressure is potentially harmful, especially if it is carried out using short
      acting dihydropyridine derivatives. Some CCBs, such as nicardipine, are preferred
      in certain conditions (including acute thrombolysis). In stroke, CCBs may also
      play a role as neuroprotectants. Then twofold effect--against vessel wall changes
      and as neuroprotectants (after ischemia or degenerative insults)--make this class
      of drugs of interest for their possible application in the setting of dementias,
      particularly that of vascular dementia. Some CCBs have been tested and are of
      benefit when used for preventing or treating cerebral vasospasm after
      subarachnoid hemorrhage. CCBs must be considered effective in preventing stroke
      in hypertensive patients. In comparison with other antihypertensive agents, their
      effects are similar to or even better than those exerted by other drugs. This may
      be due to the fact that stroke includes different types, with differing
      underlying pathophysiological mechanisms. The anti-atherosclerotic properties of
      CCBs may be useful in preventing the atherothrombotic type of stroke at the large
      pre-cerebral artery level. Dihydropyridinic derivatives may play a selective role
      in relation to small-vessel disease of the brain, which leads to multiple stroke
      associated conditions, including lacunar infarct, intra-cerebral hemorrhage and
      subcortical vascular dementia. Oral nimodipine is recommended in the
      prevention/treatment of cerebral vasospasm following subarachnoid hemorrhage
      (SAH). CCBs, particularly nimodipine, may be of some benefit in vascular or mixed
      degenerative and vascular dementia or, taking into account subtypes, more
      selectively in subcortical vascular dementia. In this setting, CCBs may
      contribute toward reducing the risk of recurrent stroke in patients who are
      usually at high risk of recurrence.

PMID- 16640171
TI  - Calcium channel blockers and nephroprotection.
AB  - The prevalence and incidence of End-Stage Renal Disease (ESRD) have progressively
      increased in the last 20 years. Hypertension and diabetes are the two most
      important causes of ESRD, and antihypertensive treatment plays a crucial role in
      preventing Chronic Renal Failure (CRF) and ESRD. The glomerulus and mesangial
      extracellular matrix are the principal sources giving rise to hypertensive
      nephropathy, which is finally characterized by progressive glomerulosclerosis.
      Several mechanisms are involved in hypertensive nephropathy, including increases
      in intraglomerular pressure and extracellular matrix production and reactive
      oxygen species (ROS)-related damage. The various activities of antihypertensive
      drugs on the kidney are particularly important in understanding their
      nephroprotective role and in developing new nephroprotective pathways in the
      future. This paper reviews the main pathophysiological aspects of renal damage in
      hypertension, the effects of various types of calcium channel blockers (CCBs) on
      renal function, and their role in nephroprotection.

PMID- 16640172
TI  - Calcium channel blockers, endothelial dysfunction, and combination therapy.
AB  - Endothelial dysfunction complicates hypertension and is a precursor of
      atherosclerosis. It is characterized by a reduction in the bioavailability of
      vasodilators, particularly nitric oxide (NO), and an increase in the activity of
      vasoconstrictors, including angiotensin (Ang) II and reactive oxygen species
      (ROS). To the extent that cardiovascular disease is characterized by an imbalance
      between NO, Ang II, and ROS in the endothelium, modulating the activity of these
      vasoactive substances has important implications for both the treatment of
      hypertension and the prevention of atherosclerosis and end organ damage.
      Accumulating experimental and clinical data suggest that a multitherapy
      antihypertensive regimen that includes inhibitors of the renin-angiotensin system
      and calcium channel antagonists may further reduce cardiovascular risk via
      greater improvements in endothelial function, in addition to the well-documented
      blood pressure lowering effects. Experimental studies in small and large coronary
      arteries and in aorta indicate that the calcium channel blocker, amlodipine,
      stimulates NO generation. These drug-specific actions beyond blood pressure
      lowering may exert cardio- and vasculoprotective effects by preventing the
      maladaptive changes that accompany hypertension, namely endothelial dysfunction,
      upregulation of proinflammatory molecules, vascular smooth muscle cell (VSMC)
      growth and migration, and increased extracellular matrix deposition, mechanisms
      that lead to atherosclerotic cardiovascular disease. These effects compliment
      those of other classes of antihypertensive agents and also 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), which have
      also been demonstrated to ameliorate the damaging consequences of endothelial
      dysfunction and thus reduce the incidence of cardiovascular events.

PMID- 16640173
TI  - Integrated cardiovascular risk management for the future: lessons learned from
      the ASCOT trial.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in Western
      countries, and hypertension-related cardiovascular events affect about 37 million
      people per year worldwide. In this perspective, treatment of hypertension is a
      reference illustrating strategies of cardiovascular prevention. Hypertensive
      patients are at increased risk of undergoing a cardiovascular event throughout
      their lives, and treatment of high blood pressure is one of the most effective
      strategies to reduce global cardiovascular risk. However, due to its
      multifactorial pathophysiology and frequent association with other important risk
      factors and clinical conditions such as dyslipidemia, diabetes, left ventricular
      dysfunction, and renal impairment, treatment of hypertension requires an
      integrated approach, including life-style measures, antihypertensive drugs and
      other therapies (statins, ASA, etc.). Nonetheless, worldwide, general
      practitioners continue to focus on managing a single risk factor, e.g. blood
      pressure, rather than on overall cardiovascular risk profiles. Another debated
      issue is whether it matters how blood pressure is lowered in hypertensive
      patients at high risk. In other words, are the latest antihypertensive drugs more
      effective than older blood pressure strategies in terms of reduction of
      cardiovascular events? The recent results of the ASCOT Study address these
      controversial issues and throw new light on the management of cardiovascular risk
      in hypertension.

PMID- 16640174
TI  - [CME -- Ultrasonography 11].

PMID- 16640175
TI  - [What is your diagnosis?].

PMID- 16640176
TI  - [Recommendations for follow-up of malignant diseases].
AB  - The follow up of patients after primary therapy of cancer is being made difficult
      by the large number of sometimes contradictory recommendations, but also by a
      lack of evidence in many diseases. A chance for cure or a longer life expectancy
      with earlier diagnosis of an asymptomatic recurrence exists in only a few
      diseases. For far more diseases, a symptom oriented follow-up with an emphasis on
      quality of life, treatment associated complications, evaluation of symptoms, and
      psychological support is recommended. In patients with a dislike of regular
      visits or in diseases without options for further treatment it will be sufficient
      if the patient returns in the case of complaints. Recommendations for follow-up
      in selected frequent cancers will be given, based mainly on the latest
      recommendations by the European Society for Medical Oncology (ESMO).

PMID- 16640177
TI  - [Sonography of the thyroid].
AB  - According to its superficial anatomical location the thyroid gland is easily
      accessible by sonography. Ultrasound is a reliable examination to detect various
      pathologies of the thyroid gland and it should always be combined with a
      sonography of the surrounding soft tissues and vessels. Sonography allows an
      exact documentation of the size, volume and parenchymal echostructure of the
      thyroid gland as well as detection of various diffuse and focal abnormalities of
      the gland itself and of the surrounding structures. The presented article gives
      an overview of the sonographic diagnoses and differential diagnoses of various
      diffuse and focal pathologies of the thyroid gland as well as some
      recommendations regarding their possible further diagnostic approach.

PMID- 16640178
TI  - [Drug-eluting stents: do they keep their promises?].

PMID- 16640179
TI  - [Dysuria and urethral discharge after travel abroad].

PMID- 16640180
TI  - [Skin eruption and flank pain in a young woman].

PMID- 16640181
TI  - [CME -- Radiology 13/Solution].

PMID- 16640182
TI  - [Seeing blue].

PMID- 16640183
TI  - [Hydrocephalic risk factors after spontaneous subarachnoidal haemorrhaging of
      aneurysmal aetiology].
AB  - INTRODUCTION: Hydrocephalus is one of the most significant complications of
      spontaneous subarachnoidal haemorrhaging that can be treated surgically.
      OBJECTIVE: We analysed risk factors that caused spontaneous subarachnoidal
      haemorrhaging. Patients were divided into two groups: shunt-dependent and shunt
      independent. METHOD: We retrospectively analysed 174 patients (63 men and 111
      women), surgically treated at the Institute of Neurosurgery of Clinical Centre of
      Serbia in the period from January 2002 to January 2004. RESULTS: The prevalence
      of hydrocephalus in patients with a shunt (shunt-dependent) was most significant
      in women (18%:9.5%), but not statistically significant (p > 0.05). Concerning the
      significance of age (years), we found that hydrocephalus in patients with a shunt
      was most significant in older patients (p < 0.025). The HiH and Fisher gradings
      were not statistically significant in our study (p > 0.05%). In patients with
      intraventricular haemorrhaging (29.3%:10.5%) and vasospasms (34.6%:6.5%), the
      prevalence of shunt-dependent hydrocephalus was statistically very significant (p
      < 0.005; p < 0.001). The frequency of ventriculomegalia in the initial CT scan
      was greater for patients with a confirmed diagnosis, but of no statistical
      significance (p > 0.05). The prevalence of shunt-dependent hydrocephalus with
      aneurysms in the a. basillaris basin was 47.4%, with multiple aneurysms 17.2%,
      and with aneurysms of the anterior segment 9.5%, which represents a statistically
      significant difference (p < 0.001). CONCLUSION: We discovered that hydrocephalus,
      as a complication of spontaneous subarachnoidal haemorrhaging, was most frequent
      in patients older than 50 years, manifesting in ventricular haemorrhaging,
      vasospasm, and aneurysms of the posterior segment.

PMID- 16640184
TI  - [Surgical revascularisation of the heart in patients with chronic ischaemic
      cardiomyopathy and leftventricular ejection fraction of less than 30%].
AB  - INTRODUCTION: Patients suffering from chronic ischaemic cardiomyopathy and left
      ventricular ejection fraction (LVEF) lower than 30% represent a difficult and
      controversial population for surgical treatment. OBJECTIVE: The aim of this study
      was to evaluate the effects of surgical treatment on the early and long-term
      outcome of these patients. METHOD: The patient population comprised 50 patients
      with LVEF < 30% (78% male, mean age: 58.3 years, range: 42-75 years) who
      underwent surgical myocardial revascularisation during the period 1995-2000.
      Patients with left ventricular aneurysms or mitral valve insufficiency were
      excluded from the study. The following echocardiography parameters were evaluated
      as possible prognostic indicators: LVEF, fraction of shortening (FS), left
      ventricular systolic and diastolic diameters (LVEDD, LVESD) and volumes (LVEDV,
      LVESV), as well as their indexed values (LVESVI). RESULTS: Fifteen patients (30%)
      died during the follow-up, 2/50 intraoperatively (4%). The presence of diabetes
      mellitus, previous myocardial infarction, main left coronary artery disease, and
      three-vessel disease, correlated significantly with the surgical outcomes. The
      patient's age, family history, smoking habits, hypertension, hyperlipidaemia,
      history of stroke, peripheral vascular disease, and renal failure, did not
      correlate with the mortality rate. A comparison of preoperative echocardiography
      parameters between survivors and non-survivors revealed significantly divergent
      LVEF, LVEDD, LVESD, LVEDV, LVESV, and LVESVI values. Preoperative LVESVI offered
      the highest predictive value (R = 0.595). CONCLUSION: Diabetes mellitus, history
      of myocardial infarction, stenosis of the main branch, and three-vessel disease,
      significantly affected the perioperative and long-term outcome of surgical
      revascularisation in patients with ischaemic cardiomyopathy and LVEF < 30%. In
      survivors, LVEF, FS, and systolic and diastolic echocardiography parameters, as
      well as their indexed values, significantly improved after surgical
      revascularisation. LVESVI provided the highest predictive value for mortality.

PMID- 16640185
TI  - [Measuring quality of life in patients with heart failure].
AB  - INTRODUCTION: The quality of life in patients with heart failure is diminished by
      symptoms of disease, affected social connections, frequent hospitalisations, side
      effects caused by medication, and costs of treatment borne by the patient
      himself. OBJECTIVE: The objective of this research was to measure the quality of
      life of patients with heart failure and assess any potential changes during a six
      month period. METHOD: This research is a follow-up study, and comprised 56
      patients who were treated from September 1998 to August 1999 at the Institute for
      Cardiovascular Diseases of the Clinical Centre of Serbia. During the first
      hospitalisation, an initial baseline measurement of quality of life was
      conducted. The measurement was then repeated after three and six months, during
      check-ups. The measurement was conducted by using a special questionnaire for
      patients suffering from heart disorders, the "Minnesota Living with Heart Failure
      Questionnaire." RESULTS: The results showed a considerable improvement in the
      overall quality of life between the baseline and second measurements (F = 6.263;
      p = 0.020), as well as considerable improvement in the physical dimension of
      quality of life between the baseline and first measurements (F = 6.797; p =
      0.016) and between the baseline and second measurements (F = 5.351; p = 0.030).
      CONCLUSION: Thanks to the application of the special Minnesota questionnaire, it
      was possible to measure small but considerable changes in the patients' quality
      of life.

PMID- 16640186
TI  - [Classic and automated blood pressure monitoring in children with scarring
      nephropathy].
AB  - INTRODUCTION: Renal scarring is the most common cause of arterial hypertension in
      children. High blood pressure (BP) and microalbuminuria contribute to the
      progression of chronic renal disease. OBJECTIVE: The aims of the study were: to
      assess BP in children with renal scarring by continuous ambulatory blood pressure
      measurement (ABPM) in comparison to the casual method (CBP), and to determine the
      correlation between ambulatory blood pressure (ABP) and/or casual blood pressure
      (CBP) values and proteinuria in children with renal scarring, METHOD: This
      forward-looking study comprised thirty-five children (26 girls and 9 boys), aged
      between 3-18 years, 10.4 +/- 3.9, X +/- SD. Blood pressure was measured using the
      casual method (CBP) with a mercury manometer; BP was measured three times and the
      average was taken as a referent value. ABPM was performed using the oscillometric
      method with the SpaceLabs device, model 90207. RESULTS: 45.71% of patients were
      classified as hypertensive by ABPM, while only 22.6% of CBP measurements were
      above the 95th percentile (p < 0.01). "White coat hypertension" was present in
      40% of the patients. Non-dipping BP alteration was detected in 37.14% of the
      patients. CONCLUSION: Nocturnal systolic hypertension (systolic non-dipping
      alteration) is very frequent in children with renal scarring. Nocturnal diastolic
      blood pressure, detectable only via ABPM, is positively correlated with
      proteinuria and may be an initial sign of the progression of renal scarring. ABPM
      is more sensitive than CBP in the evaluation of BP in children with renal
      scarring.

PMID- 16640187
TI  - [Autogenic training as a therapy for adjustment disorder in adolescents].
AB  - INTRODUCTION: Autogenic training is a widespread technique used in psychotherapy.
      The British school of autogenic training cites a large list of diseases, health
      states, and life changes, in which autogenic training can be of help. We wanted
      to explore the application of autogenic training as a therapy for adjustment
      disorder in adolescents. The sample consisted of a homogeneous group of 31
      individuals, with an average age of 17.3 +/- 0.2 years, who were diagnosed with
      adjustment disorder, F 43.2, in accordance with ICD 10 search criteria.
      OBJECTIVE: The aim of our work was to figure out the influence of autogenic
      training on adjustment disorder, through biophysical and biochemical indicators,
      and to research the efficiacy of autogenic training as a therapy for adjustment
      disorder in adolescents. METHOD: We observed adjustment disorder indicators and
      their changes in three phases, using initial, final, and control values, which we
      measured immediately before the beginning, immediately after the completion, and
      six months after the completion, of the practical course in autogenic training.
      We measured systolic and diastolic arterial blood pressure, brachial pulse rates,
      cortisol levels in plasma, cholesterol levels in blood, as well as glucose
      concentrations. During that period, autogenic training was employed as the sole
      therapy. RESULTS: The study confirmed our preliminary assumptions. The
      measurements we performed showed that arterial blood pressure, pulse rates,
      cholesterol and cortisol concentrations, after the application of autogenic
      training among adolescents suffering from adjustment disorder, were lower than
      the initial values. They remained lower even six months after the completion of
      the practical course in autogenic training. CONCLUSION: We concluded that
      autogenic training significantly decreases the values of physiological indicators
      of adjustment disorder, diminishes the effects of stress in an individual, and
      eases the adaptation of adolescents to stress, helping with recovery.

PMID- 16640188
TI  - [Influence of proprioceptive training in the improvement of neuromuscular
      performance after ACL reconstruction].
AB  - ACL injury leads to a decrease in proprioceptive abilities, which can be improved
      with ACL surgery and postoperative rehabilitation. The goal of our study was to
      investigate whether the impact of coordinative training can be differentiated
      from the influence of surgery on proprioceptive improvement, and whether there is
      a correlation between improvement in coordinative abilities and other objective
      parameters of functional recovery. This follow-up study included 45 patients who
      had undergone ACL reconstruction and who were randomised into a conservative (TH
      C) and an intensive (TH-I) rehabilitation group. In the TH-I group, coordinative
      training began earlier due to unrestricted weight-bearing. The groups were first
      compared preoperatively, then postoperatively, after 6 weeks, 4, 6, 9, and 12
      months via the single leg stance test, the one leg hop test, the Lysholm knee
      score, and the Tegner score. A faster recovery of coordinative skills was
      registered in the TH-I group. Already after 6 weeks, highly statistically
      significant progress in one leg stance abilities was noticed, while in the TH-C
      group the same was not noticed until 4 months after surgery (p < 0.01). Such a
      result speaks for the distinct influence of proprioceptive training on
      coordinative abilities. Also, a highly statistically significant correlation was
      noticed between the single leg stance, one leg hop, Lysholm, and Tegner tests (p
      < 0.01), which points out the importance of a good rehabilitation programme,
      since neuromuscular performance cannot be separated from other parameters of
      functional recovery.

PMID- 16640189
TI  - [Bilateral angiomyolipoma of the kidney in patient with tuberous sclerosis].
AB  - Angiomyolipomas are relatively frequent tumours of the kidney. It is believed
      that about 10 million people worldwide have such a tumour. About 1/10 of these 10
      million are patients who suffer from tuberous sclerosis. The tumours are
      frequently bilateral, slow growing, and usually asymptomatic, as well as being
      rare in children. Due to the benign nature of angiomyolipomas, surgical treatment
      and embolisation of the tumours are generally not recommended, unless renal
      function is endangered, the symptoms are severe, or the kidney in question
      becomes completely dysfunctional. This is particularly the case in patients with
      tuberous sclerosis in whom these tumours are either already bilateral or may
      become so. We present a 24-year-old woman with tuberous sclerosis in whom
      bilateral kidney tumours were diagnosed 7 years earlier and in whom we carried
      out a left nephrectomy of a 5300 gram angiomyolipoma, which caused pain and
      complete loss of function. Although tumourous, the right kidney was functional,
      so it was left untouched. After an uneventful recovery, a close follow-up was
      recommended, as well as HLA typing, as it is highly probable that the right
      kidney will gradually become inadequate or completely dysfunctional, so that
      haemodialysis and/or kidney transplantation along with nephrectomy will become
      necessary.

PMID- 16640190
TI  - [Multiple endometrial polyps in patient undergoing long-term gestagen therapy].
AB  - Endometrial polyps represent a limited focal, circumscribed overgrowth of the
      endometrium. Their aetiopathogenesis has not been completely explained yet. They
      are often found in perimenopausal women; during the reproductive period they are
      less common. We present the case of a 32-year-old patient, who came for a check
      up to the Gynaecology and Obstetrics Clinic "Narodni Front" because of irregular
      bleeding. The patient was subjected to hormonal linestrenol therapy, which she
      had administered herself, without further consultations with her gynaecologist,
      during the previous 10 years. Complete diagnostic examinations were performed.
      Contrast sonohysterography enabled the visualisation of multiple polyps inside
      the uterine cavity, which were confirmed by histopathological analysis of
      material obtained via explorative curettage. Histopathological material contained
      over 30 endometrial polyps. A control check-up after one month, as well as
      subsequent quarterly check-ups, resulted in normal findings. Analysis of the
      described case has indicated that the loss of sensitivity of progesterone
      receptors in endometrial cells is possible if there is a continuous presence of
      progesterone agonists in circulation, as is true of linestrenol in this case. The
      loss of sensitivity of progesterone receptors upsets normal hormonal activity
      during the secretory phase of the menstrual cycle, leading to copious, irregular
      bleeding. These changes may, however, have even deeper effects. More recent
      research shows that, if the agent causing the loss of sensitivity of the
      receptors is present in circulation over a longer time period, changes may also
      appear at the DNA molecular level, i.e. in the cell genome itself. This, in turn,
      may lead to the beginning of the process of oncogenesis and the formation of
      tumourous tissue.

PMID- 16640191
TI  - [Adipose tissue as an endocrine organ].
AB  - The traditional function attributed to white adipose tissue of energy storage in
      the form of triglycerides has been challenged by results from recent studies,
      showing that adipose tissue is, in fact, a highly active metabolic and endocrine
      organ. A radical change in perspective followed the discovery of a large number
      of proteins secreted from white adipocytes, such as leptin, resistin,
      adiponectin, adipsin, acylation-stimulating protein, angiotensinogen, tumour
      necrosis factor a, interleukin-6, retinol-binding protein, plasminogen activator
      inhibitor-1, tissue factor, fasting-induced adipose factor,
      fibrinogen/angiopoetin-related protein, and metallothionein. The effects of
      specific proteins may be either autocrine or paracrine, meaning that they might
      act in adipose tissue itself or in more distant target tissues. Some of these
      proteins induce insulin resistance, some play a role in glucose and lipid
      metabolism, some are inflammatory cytokines, while others are involved in
      vascular haemostasis. The key challenges for future investigations of adipose
      tissue's secretory functions will be to identify all of its secreted proteins, to
      establish the function of each secreted protein, and to assess the
      pathophysiological consequences of changes in adipocyte protein production due to
      problems, such as obesity, fasting, or diabetes mellitus type 2.

PMID- 16640192
TI  - [Surgical therapy for stress urinary incontinence].
AB  - Stress urinary incontinence (SUI) is a common disorder among women of all ages,
      which compromises their quality of life. It may compromise self-esteem, restrict
      lifestyle, strain relationships, and may ultimately lead to social embarrassment
      and isolation. Therefore, SUI management does not only imply cure or improvement
      of SUI, but also includes psychological and social assistance to help sufferers
      to cope with their condition. In this regard, it is important to acknowledge the
      role of the patient in the selection of an appropriate treatment. Physicians and
      patients can choose between conservative, pharmacological, and surgical
      treatments. Surgical techniques for SUI have evolved over the last 150 years.
      Accurate diagnosis of SUI is essential before surgery is undertaken. Many
      surgical procedures have been employed, which can be divided into four basic
      types: anterior colporrhaphy, colposuspensions, suburethral sling procedures,
      including TVT, as well as suburethral bulking agents. This wide variety of
      surgical procedures indicates the lack of consensus on which procedure is best.
      In most continence surgery, the benefit of restoring continence often comes at
      the expense of instigating new symptoms or exacerbating existing lower urinary
      tract symptoms.

PMID- 16640193
TI  - [Max Josef von Pettenkofer--founder of modern hygiene (1818-1901)].
AB  - Max Josef von Pettenkofer was one of the leading personalities in the world of
      medicine in the 19th century. He was the founder of the modern science of
      hygiene. In his experimental work, he was involved in the research of problems
      dealing with the relationship between human beings and the environment, including
      such topics as soil and air pollution, water supply, sewage water management,
      room ventilation and heating, as well as the function of clothing and the
      cleanliness of homes and streets. Pettenkofer also studied the onset, the course,
      and the consequences of infectious diseases, such as cholera and typhus. He
      realised the great economic value of public health and emphasised that personal
      preventive measures should be supplemented with the improvement of factors in
      communal and work environments. His efforts lead to hygiene becoming a part of
      medical studies in 1865. The Institute for Hygiene at the School of Medicine in
      Munich was established in 1879. It was constructed according to his drawings and
      was considered to be the most modern institute for hygiene in the world. Since
      hygiene was a subject on the school curriculum in the German Empire in 1882,
      Pettenkofer became the Chairman of Hygiene in Berlin in 1885. Research
      institutions established by Pettenkofer and the fact that many of his students
      became professors of hygiene speak about the importance of his work. One of his
      students was professor Milan Jovanovic Batut, founder of the Institute for
      Hygiene at the School of Medicine in Belgrade.

PMID- 16640195
TI  - [Lipids composition diet in phenylketonuric children with early diagnosis].
AB  - Phenylketonuria (PKU) is a genetic disorder caused by a partial or complete
      mutation of the enzyme phenylalanine hydroxylase (PHA), fact that produces high
      levels of phenylalanine in blood resulting in mental retardation if not diagnosed
      during the neonatal period. Treatment consists of a phenylalanine (Phe)
      restricted diet. Several studies have shown that due to restriction of animal
      protein, this diet is deficient in fatty acids such as alfalinolenic acid (ALA)
      and provides high levels of linoleic acid (LA). The objective of this study was
      to determine the lipid composition of the diet consumed by children with early
      diagnosed PKU. Lipid composition of the Phenylalanine restricted diet consumed by
      29 children with PKU and in follow-up at INTA, University of Chile, were
      analyzed. Children were paired by sex and age with a control group. A twenty-four
      hour dietary recall was performed for 3 consecutive days and total fatty acid
      intake, including saturated, monounsaturated, polyunsaturated, LA and ALA, were
      calculated. In the restricted diet of children with PKU, 31.8% of total calories
      are from fat, 13% of which are LA and 0.2% ALA, showing significant differences
      as compared to the control group. The ratio of
      saturated:monounsaturated:polyunsaturated fatty acids was 1:1.7:3.9 and the ratio
      of LA:ALA was ten-fold higher than the recommended ratio of 115:1. It is
      concluded that the Phenyalanine restricted diet of Chilean children with PKU is
      high in LA and low in ALA.

PMID- 16640194
TI  - [Key informants assessment on the action plan of food security policy in
      Colombia].
AB  - A descriptive study by a cross-sectional structured survey to137 IC: 17 policy
      makers, 32 civil servants and 88 communities-beneficiaries (41 vulnerable
      groups(VG) and 47 rural-homes-groups(RHG)) to assess the 1996-2005 Colombian Food
      and Nutrition National Plan (FNNP) using key informants (KI) of the security food
      programme directed to VG and RHG has been done. VARIABLES STUDIED: food security
      (FS) operation, coverage and benefits programme. An Index of Position (IP) to
      quantify the assessment of the KI (0 = positive valuation at 1 = negative)
      opinions was built. The KI know the programmes directed to VG (IP = 0 at 0,44)
      better than the directed to RHG (IP = 0,43 at 0,73). The FS programmes for GV
      improve the nutritional status (IP = 0,07) and health (IP = 0,13) and that
      contributes to create self-companies (IP = 0,23). The HRG programmes increase the
      food production (IP = 0,30) and improve the technical consultantship (IP = 0,30).
      The operation of the programmes of community-child-care-homes are valued as
      excellent by the users (IP = 0,16). It concludes that the productive programmes
      to rural groups are less well-known than the supplemental food programmes for
      vulnerable groups. There is no consensus of the assessment of the operation and
      benefits among the key informants, being the users who better value them,
      especially of their development participation. That is also perceived as more
      covers the poor and vulnerable target population.

PMID- 16640196
TI  - [Treatment of severe malnourished children with WHO protocol: experience of a
      referral center in Sao Paulo, Brazil].
AB  - Mortality rate, anthropometric development and nutritional therapy with the use
      of World Health Organization guidelines (WHO) were assessed. In a cross-sectional
      retrospective study 191 hospitalized malnourished children were assessed. To
      classify and evaluate nutritional rehabilitation Z-score was used: weight-for-age
      (ZW), height-for-age(ZH) and weight-for-height(ZWH). The children were divided in
      three groups (G): GI (primary malnutrition--30,9%), GII (secondary malnutrition-
      51,7%) and GIII (children who were admitted as GI but during internation had an
      identified chronic disease--12%). Nutritional therapy used was based on WHO
      guidelines, with slight modifications. The formulas chosen were all
      industrialized: lactose-free polymeric formula (PLF) for children with diarrhea,
      low lactose polymeric formula (PLL) for children without diarrhea and cow's milk
      hydrolysate (H) for sepsis or chronic diarrhea. In the rehabilitation phase, all
      the children used PLL formula. STATISTICAL ANALYSIS: Student's, chi-square tests,
      simple linear regression. The median age and mortality rate were 10,3 months and
      4,2%, respectively. The GI and GII children were older than GIII
      (11vs12vs7months,p=0,02) and had shorter length of stay (20vs22vs37days,p=0,010).
      Mortality risks in GIII were twice as frequent as in GI+GII. Pneumonia, diarrhea
      and poor weight gain were the main diagnosis at admission. Tubes were used more
      frequently in GII+GIII than GI (p=0,004). Parenteral nutrition was indicated in
      5,7% of children, more often in GIII than GI+GII (p=0,037). Tolerance of the
      initial formula wasn't satisfactory in 20% of the children. An improvement of 87%
      ZWH, 74,1% ZW and 22% was observed. ZW in GI and ZWH in GIII were the indices
      that showed the most effective gain during hospital stay. The modified WHO
      guidelines were effective in the multiprofessional treatment of malnourished
      children, resulting in good nutritional rehabilitation with low mortality rates.
      A high percentage of children admitted as primary malnutrition who had a chronic
      disease diagnosed was observed. The late diagnosis may be responsible for the
      high length of stay, formula intolerance and mortality risk.

PMID- 16640197
TI  - Relationship between calcium intake and body mass index in adolescents.
AB  - Epidemiologic and experimental data support thee possibility that dietary calcium
      intake plays a role in human body weight regulation. The aim of the present study
      was to evaluate calcium intake and its relationship with body mass index (BMI) in
      adolescents. Weight, height, 3-day food record and a food frequency questionnaire
      were collected among all adolescents participants at the Outpatient Clinic for
      Adolescents at the Federal University of Sao Paulo between 2001 and 2003. The
      statistical analysis comprised Chi-square, Student's T-test, Pearson correlation
      and linear regression. One-hundred and twenty-one adolescents were studied (62.8%
      female), with a mean age of 14.9 +/- 2.2 years old. Mean energy and calcium
      intakes were 1729.9 +/- 557.8 kcal/day and 598.2 +/- 287.9 mg/day respectively,
      with no significant statistical differences between sex or age. Almost ninety
      eight percent of adolescents presented a mean calcium intake lower than proposed
      values. Calcium intake adjusted for energy presented a significant negative
      correlation with body weight (r=-0.194, p=0.03) and BMI (r=-0.185, p=0.04).
      Furthermore, adolescents in the lowest quartile of calcium intake presented
      higher BMI (29.7 +/- 7.4 kg/m2) than adolescents in the highest calcium quartile.
      These results indicated a dietary calcium intake lower than recommendations for
      this life stage, and a contribution of this mineral in the body mass index.

PMID- 16640198
TI  - [Viability of a native isolate of Lactobacillus brevis in a fermented milky
      drink].
AB  - The objective of this research was to test the viability of a native isolate of
      Lactobacillus brevis in two fermented milky drinks: a drink without prebiotic
      ingredient and another drink with oat flour (0.5%, p/v) as prebiotic ingredient.
      The viability of L. brevis was tested at 7, 14, and 21 after inoculation. Drink
      pH and lactic acid concentration was measured as a function of time (2, 7, 14,
      and 21 days after inoculation). The isolate was viable in both drinks because its
      counting plates was higher than 10(6) CFU/mL until day 21st. Between the 7th and
      14th day, the rate of growth was higher in the drink that included oat flour,
      however, at the day 21st the colony density was similar in both drinks.

PMID- 16640199
TI  - [Influence of maize kernel hardness on flour hydration and cooking properties].
AB  - Knowledge of the association between cooking properties and endosperm hardness
      may help nutritionist and processors to select raw materials for preparing maize
      based food products, particularly those eaten as cooked dispersions. Seven
      commercial maize cultivars differing in hardness were selected to evaluate
      endosperm hardness on the kernels and some characteristics such as composition
      and hydration and cooking properties on the grits obtained from those maizes.
      Results show that the differences in endosperm hardness (directly related to
      grits protein content) can explain the differences in swelling and amylographic
      consistencies values. Cultivars with the hardest endosperm show the lowest values
      at high temperature. They also show the lowest amylographic consistencies. On the
      other hand softer endosperms present the highest swelling power and the highest
      amylographic consistencies. These differences are attributed to the restriction
      for starch swelling caused by the protein matrix. Endosperm hardness measurements
      and swelling power at 95 degrees C, can be useful to select cultivars that are
      going to be used to prepare maize based foods like atoles, polenta, etc.

PMID- 16640200
TI  - [Iron concentration and acceptation of yoghurt prepared in casting iron pots
      (iron migration and acceptation of yogurt)].
AB  - Food fortification is an interesting strategy to treat and prevent iron anemia.
      This study aims to quantify the iron in yoghurt, with gelatin and sugar and
      without, prepared in iron and glass containers. Sensorial test was use to
      evaluate the acceptance and preference of the both products. The yoghurt was
      prepared in containers of iron and glass with UHT milk, powder milk and natural
      industrialized yoghurt. After fermentation, half of the product received addition
      of sugar and strawberry flavor gelatin. The collected samples get the total iron
      quantified by ICP OES. Sensorial analysis involving 105 consumers was use to
      determine the acceptance and preference of the products. 0,018 and 0,882mg of
      iron per 100g added in the natural yoghurt prepared in the glass and in the iron
      pots, respectively. The yoghurt with gelatin presented 0,037 and 1,302mg of iron
      per 100g when prepared in the glass and in the iron pots, respectively. The
      preference was low for the yoghurt prepared in the iron pot (29,5%), but when
      added strawberry gelatin it was about 51,5%. The yoghurt prepared in iron pots,
      is easily home made and adds important amount of iron. Add gelatin and sugar can
      favored its consumption.

PMID- 16640201
TI  - [Margarine's trans-fatty acid composition: modifications during the last decades
      and new trends].
AB  - Trans fatty acids isomers are formed during the hydrogenation process used in the
      food industry to harden oils. In the last decades there has been a great
      controversy about the consumption of margarine due to the levels of trans fatty
      acids they contain. While in the eighties consumption of margarines was
      considered healthy, during the nineties several studies indicated that
      consumption of 18:1t increased LDL-cholesterol levels and decreased HDL
      cholesterol level, and was related with an increased risk of coronary heart
      disease. The publicity about the unfavourable effects of trans fatty acid
      consumption seems to have influenced margarine producers to reduce the trans
      fatty acid content of margarines. Meanwhile USA has adopted a new legislation
      about trans fatty acid labelling. In Europe, Dinamarca has limited the maximum
      level of trans fatty acids allowed in food products.

PMID- 16640202
TI  - [Organoleptic and physicochemical characteristics of propolis in the Province Of
      Nuble, VIII Region-Chile].
AB  - Propolis ("bee-glue") is a gummy resinous substance elaborated by honey bees
      (Apis mellifera) from different types of plant resins. The chemical composition
      of propolis is very complex and variable as it depends on the botanical source
      and the environmental conditions prevailing at the location where the resin is
      collected by bees. The objective [corrected] of this study was to determine the
      propolis organoleptic and physicochemical properties of different types in the
      Province of Nuble (VIII Region, Chile). Samples were collected at different sites
      located in the Central Valley, ranging from the coast to the mountain skirts.
      Analyses included humidity, ashes, wax content, total phenolics content, total
      flavonoids, mechanical impurities, oxidation time, and solubility in ethanol.
      Results showed that propolis extracts from coastal sites are better quality than
      those collected at mountain skirts, and these in turn are better than propolis
      obtained from the Central Valley. All propolis analyzed in this study can be
      classified according to the Brazilian norm as high flavonoid content. The same
      homogeneity is observed in the amounts of total phenolics found in the samples.
      In general terms, properties of the propolis samples analyzed fulfill the quality
      requirements of the current international standards.

PMID- 16640203
TI  - What now for NHS direct?

PMID- 16640204
TI  - Long-distance 'no-touch' nursing cannot replace hands-on care.

PMID- 16640205
TI  - Counting the cost of cuts.

PMID- 16640206
TI  - Providing end-of-life care for people with learning disabilities.
AB  - The end-of-life care model Preferred Place of Care and the philosophy known as
      person-centred planning both aim to make patient choices and views central to any
      service delivery. This article compares the two strategies.

PMID- 16640207
TI  - Post-traumatic stress disorder.

PMID- 16640208
TI  - Homeostasis part 2: acid-base balance.

PMID- 16640209
TI  - The nurse's role in assessing and measuring spasticity.
AB  - Spasticity is a common feature of neurological conditions such as multiple
      sclerosis, cerebral palsy, stroke, brain and spinal injuries. The management of
      spasticity remains a challenge for not only the person with spasticity but also
      their family, carers and healthcare professionals. Accurate assessment and
      measurement is essential to ensure individuals receive the most appropriate
      interventions.

PMID- 16640210
TI  - Alzheimer's cafe for people with and affected by dementia.
AB  - Discussing emotional trauma is a central part of care in dementia and can help
      individuals value and make sense of their lives. The Alzheimer's cafe, started in
      1997 in the Netherlands, can help facilitate this. This article reviews an
      adapted version of an Alzheimer's cafe focusing on eight couples where one
      partner was newly diagnosed with dementia. It is primarily a reflective account.

PMID- 16640211
TI  - A study of senior staff nurses' perceptions about MRSA.
AB  - AIM: To examine the extent to which staff nurses feel that MRSA is out of control
      and that any attempts by them to control it are unnecessary. METHOD: A
      qualitative research paradigm with semi-structured interviews to examine the
      perceptions, attitudes and beliefs of 10 senior staff nurses. RESULTS: In the
      study, 60% of participants believe that MRSA is out of control and state 'why
      should they bother worrying about it'. Furthermore, 80% of participants commented
      that prescribed courses of nasal mupirocin were frequently missed. The perception
      is that IV treatments were more important and effective than topical agents.
      CONCLUSION: The study has established that a small section of experienced staff
      nurses perceive MRSA to be out of control and they are not overly concerned about
      its management.

PMID- 16640212
TI  - Intra-uterine progestogen system.

PMID- 16640213
TI  - Bridging the theory-practice gap: developing new approaches to clinically-led
      education in cancer care.

PMID- 16640214
TI  - Nursing research at the Royal Marsden NHS Foundation Trust.
AB  - The Royal Marsden has a prestigious cancer-related research programme with a
      commitment to developing nursing research. Nurses are able to make an important
      contribution to cancer care through their close relationship with patients, which
      gives them a unique research perspective.

PMID- 16640215
TI  - Developing advanced nursing practice roles in cancer care.
AB  - Nurses in cancer care have been at the forefront of developing advanced nursing
      practice, however there has not been national agreement in relation to the
      education and clinical skills required for this practice. Work is under way by
      the NMC to develop a regulated framework for the standard for post-registration
      nursing.

PMID- 16640216
TI  - Developing cancer education at the Royal Marsden School.
AB  - The Royal Marsden School of Cancer Nursing and Rehabilitation has developed a
      range of educational programmes to meet the needs of nurses and allied health
      professionals working in cancer care and to address the UK's shortage of
      appropriately trained cancer care specialists. The educational programmes are
      aimed at a wide range of practitioners at all levels--from newly qualified to
      consultant. The school has also provided education for nurses working in district
      general hospitals, with the aim of improving patient care for all people with
      cancer--in whatever setting they are treated.

PMID- 16640217
TI  - A sign of understanding. Interview by Jaida Miah.

PMID- 16640218
TI  - An opportunity to empower women.

PMID- 16640220
TI  - [European Resuscitation Council guidelines for cardiopulmonary resuscitation in
      2005].
AB  - ADULT BASIC LIFE SUPPORT: The ratio of compressions to ventilations is 30:2 for
      all adult victims of cardiac arrest. AUTOMATED EXTERNAL DEFIBRILLATION: A single
      defibrillatory shock is delivered, immediately followed by two minutes of
      uninterrupted CPR. ADULT ADVANCED LIFE SUPPORT: In out-of-hospital cardiac arrest
      attended, but unwitnessed, by healthcare professionals equipped with manual
      defibrillators, give CPR for 2 minutes before defibrillation. The recommended
      initial energy for biphasic defibrillators is 150-200 J, for second and
      subsequent shocks is 150-360 J. The recommended energy when using a monophasic
      defibrillator is 360 J for both the initial and subsequent shocks. Rhythm checks
      must be brief, and pulse cheks undertaken only if an organised rhythm is
      observed. Adrenaline is given 1 mg i.v. as soon as intravenous access is
      obtained, and repeated every 3-5 min thereafter until return of spontaneous
      circulation is achieved. Consider thrombolytic therapy when cardiac arrest is
      thought to be due to proven or suspected pulmonary embolus. Unconscious adult
      patinets, with spontaneous circulation, after out-of-hospital VF cardiac arrest
      should be cooled to 32-34 degrees C for 12-24 hours. PAEDIATRIC BASIC LIFE
      SUPPORT: Lay rescuers or lone rescuers witnessing paediatric cardiac arrest will
      start with 5 rescue breaths and continue with the 30:2 ratio as thaught in adult
      BLS. Two or more rescuers with a duty to respond will use the 15:2 ration in a
      child up to the onset of puberty. PAEDIATRIC ADVANCED LIFE SUPPORT: When using a
      manual defibrillator, a dose of 4 J/kg (biphasic or monophasic waveform) should
      be used for the first and subsequent shocks. Adrenaline iv. or i.o. should be
      given at the dose of 10 microg/kg (0.01 mg/kg) and repeated every 3-5 minutes.
      NEONATAL LIFE SUPPORT: Protect the newborn from heat loss. Standard resuscitation
      in delivery room should be made with 100% oxygen. Suctioning meconium from the
      baby's nose and mouth before delivery of the baby's chest (intrapartum
      suctioning) is not useful and no longer recommended.

PMID- 16640221
TI  - [Correlation between children's weight and height at medical examination on
      enrolling in 1st class of primary school and birth growth parameters with
      parental heights].
AB  - Physical growth is permanently influenced by genetic and environmental factors.
      Their impacts are overlapping, and therefore it is difficult to separate the
      contribution particularly ascribable to one or another kind of the factors. The
      study investigated the relation between body weight and height in 397 children
      (195 girls and 202 boys) enrolling primary school and their birth growth features
      on the one side, and their parents' heights on the other. The correlations
      between children's weight and height on enrolling primary school and their birth
      growth features were also studied. The aim was to examine the proportion of
      genetic determinacy of children's growth. Mean birth weight and length were 3440
      +/- 413 g and 50.50 +/- 2.00 cm, respectively, and mean head circumference was
      34.50 +/- 1.20 cm. On entering the primary school, the children were 6.70 +/-
      0.30 years of age in average, and had mean body weight and height of 24.60 +/-
      5.00 kg and 122.70 +/- 6.15 cm, respectively. Majority of children had both
      parents with middle or low education level, 285 (71.79%) of them. Majority of
      children also had both parents employed. 266 (67.00%) of them. Children's height
      on enrolling the school was in significant positive correlation with birth
      weight, length and head circumference, and with parents' heights. The correlation
      coefficient was the highest with father's height (r=0.473, p<0.01), and the
      lowest with birth weight (r=0.158, p<0.05). Children's weight on enrolling the
      school significantly positively correlated with the three birth growth features
      and with father's height, but not with mother's height (r=0.091, p>0.05). The
      correlation coefficient was the highest for father's height (r=0.288, p<0.01)
      again. All the birth parameters correlated stronger with mother's than with
      father's height. In the subgroup of children whose mothers were of equal or
      greater height than fathers (n=28), correlation coefficient between children's
      and fathers' heights (r=0.295, p<0.01) was lower than between children's and
      mothers' heights (r=0.474, p<0.01). In conclusion, children's weight and height
      at the time of enrolling primary school significantly positively correlates with
      their parents' heights. The correlations are stronger with father's height.
      Though, it is not the matter of gender, but of the higher parent. The birth
      growth parameters are only in part related to parents' heights (all three with
      mother's and only one with father's height). It is obvious that mothers'
      influence is dominant for children's growth at that time. There was no
      significant difference in any examined parameter between subgroups of children
      divided according to their parents education level and employment status.

PMID- 16640222
TI  - [Unsuspected posterior mediastinal paraganglioma--anesthetic risk].
AB  - A 70-year old female patient was admitted to the hospital because of scheduled
      thoracotomy and biopsy of posterior mediastinal retrocardiac tumor of
      unrecognized etiology. The patient had no complaints regarding the tumor. Routine
      anesthesiological preoperative examination revealed status ASA III. Induction in
      anesthesia was usually stable. At the moment when the surgeon intraoperatively
      touched the tumor, hemodinamic instability started and arterial blood pressure
      and heart rate dramatically increased. Our first reaction was to deepen the
      anesthesia. Very soon it was obvious that blood pressure increased by the
      surgeon's manipulation of the tumor and we started to doubt on catecholamine
      secreting tumor. During the course of the operation there were several
      hypertensive episodes and we managed them by alternately using atenolol,
      glyceroltrinitrate and anesthetic drug. The patient was extubated 5 hours after
      transfer to the intensive care unit. Postoperative period was hemodynamically
      stable. The level of catecholamines in 24-hour urine collection was significantly
      increased. Pathohistologic diagnosis was mediastinal paraganglioma.

PMID- 16640223
TI  - [Thyroglossal duct cyst in hyoid bone].
AB  - The thyreoglossal cyst may be located in the intralingual, suprahyoid, thyrohyoid
      or suprasternal region. Its position in the hyoid bone is extremely rare. In this
      paper a 62-year-old patient with a big thyreoglossal duct cyst situated in the
      corps of the hyoid bone is described. Besides a painless solid swelling in the
      medial neck region, the patient had swallowing and breathing problems, which is
      unspecific for thyreoglossal duct cyst. By removing the hyoid bone with
      thyreoglossal duct cyst, the patient's problems completely disappeared and during
      1 year long observation no sickness relapse has been noted.

PMID- 16640224
TI  - [Complementary obstetrical delivery methods].
AB  - Complementary methods in obstetrics are related to humanization of delivery and
      woman's decision on the mode of delivery in normal labor. The methods include
      various birthing positions, aids such as delivery chair, birthing wheel, etc.,
      and water delivery. Results of recent studies comparing these methods with
      classic delivery in supine position are presented. The advantages of these
      alternative methods of delivery include shorter duration of delivery, reduced
      need of labor induction, lower use of analgesics, and women's acceptance of these
      methods of delivery with the same level of maternal and neonatal safety as in
      classic delivery. All these advantages apply to water delivery providing the
      prerequisities, contraindications and measures of surveillance are strictly met.

PMID- 16640225
TI  - [Fulvestrant: a new agent in endocrine treatment for breast cancer].
AB  - Tamoxifen is considered to be the gold standard in hormonotherapy of patients
      with estrogen dependent breast cancer (estrogen receptor (ER) and/or progesterone
      receptor (PR) positive tumors). However, because tamoxifen's beneficial effects
      diminish after 5 years of use in adjuvant setting and because of its partial
      agonistic effects and its resistence to tamoxifen in some breast carcinoma, there
      is a need for new antiestrogens. One of these antiestrogens is fulvestrant which,
      unlike tamoxifen, has no partial agonistic effects. Its efficacy has been
      confirmed in preclinical and in recent phase III clinical studies in
      postmenopausal patients. In disease recurrence after adjuvant tamoxifen or
      progressive disease on-first-line tamoxifen treatment fulvestrant is comparable
      with (similar to) anastrozole. When compared with tamoxifen as first-line
      treatment in patients with advanced cancer, only in patients with ER and/or PR
      positive tumors similar results have also been obtained. In both trials tolerance
      to fulvestrant has been good. Following the results of these clinical studies
      fulvestrant has already been licenced in the USA and EU for the treatment of
      postmenopausal women with advanced breast cancer who had progressed on prior anti
      estrogen therapy.

PMID- 16640226
TI  - [Rituximab in the treatment of B-cell non-Hodgkin lymphoma].
AB  - Rituximab, a chimeric anti-CD20 monoclonal antibody, has become a part of
      standard treatment of B-cell non-Hodgkin lymphoma in the last several years.
      Depleting CD20+ cells by various mechanisms, it is active as a single agent and
      particularly when combined with chemotherapy. It is effective in "in vivo"
      elimination of neoplastic cells from the hematopoetic stem cell transplant. Side
      effects are mostly infusion related, mild to moderate, mediated by cytokine
      release. Because of different mechanisms of action, adding rituximab to
      chemotherapy does not cause additional toxicity. Combination of rituximab and
      chemotherapy improves response rates in indolent lymphomas and survival in
      aggressive lymphomas.

PMID- 16640227
TI  - [Characteristics of autologous peripheral blood stem cells in pediatric
      patients].
AB  - Autologous peripheral blood stem cells are increasingly used for transplantation
      instead of bone marrow, even in small children and adolescents. We analyzed 73
      autologous leukaphereses performed in 25 children (36% males, 64% females). The
      median age was 15 years (range 3-18) and the median body weight 48 kg (range 16
      67). The apheresis procedures were carried out with cell separator COBE Spectra.
      Each patient underwent a median of 2 collections (range 1-6). The median total
      nucleated cell yield was 11.86x108/kg (range 1.94-21.21), mononuclear cell yield
      was 6.01x10(8)/kg (range 0.97-12.73) and CD34+ cell yield was 3.5 x10(6)/kg
      (range 0.19-28.01). During 6 (8.22%) procedures the patients had experienced
      apheresis-related side effects. The citrate-induced reactions were most commonly
      observed. The reactions were mild and cessation of collection was required only
      in one case, because of catheter related complication. Our results show that
      leukapheresis in pediatric patients is a safe procedure, well tolerated and with
      a very low risk of serious adverse events.

PMID- 16640228
TI  - [Inflammatory bowel disease and pregnancy].
AB  - Inflammatory bowel diseases (IBD) can affect women of childbearing potential.
      There are many issues to consider in female patients with IBD who are
      contemplating pregnancy, such as influence of the disease on fertility or
      pregnancy outcome, effect of the gestation on the course of the disease, safety
      of the drugs and inheritance of the disease in the offspring. It is important to
      remember that the outcome of the pregnancy is dependent mostly on the activity of
      the disease at the time of conception and there is no increase of the adverse
      events in patients with quiescent bowel disease. With few exceptions, majority of
      medications used in the treatment of IBD are safely used during pregnancy and
      breastfeeding. This article reviews the most recent knowledge regarding the
      effects of IBD and their treatment on fertility and pregnancy, therapeutic
      options and outcomes in patients who are planning pregnancy or who are pregnant
      or lactating.

PMID- 16640229
TI  - [Nature of expert knowledge--psychological research].
AB  - The nature of expert knowledge is explored from two points of view. One of them
      questions the possibility of expert judgement making in practice and analyses the
      possible origins of bias of professional decision making. The second approach
      assumes that expertise manifests in different approaches in solving problems
      between beginners and experts who have proven high competence in the field.
      Shanteau's analysis of particular fields of expertise which shows differences in
      validity and reliability of professional decision making was also described.
      These differences to large extent can be attributed to different characteristics
      of problems specific to a particular field. In The last section of the paper
      gives an overview of the research results considering the origins of bias in
      medical expertise.

PMID- 16640230
TI  - [Female urethra and anatomical pelvic support].

PMID- 16640232
TI  - History from the ground up: bugs, political economy, and God in Kirby and
      Spence's Introduction to Entomology (1815-1856).
AB  - William Kirby and William Spence's Introduction to Entomology is generally
      recognized as one of the founding texts of entomological science in English. This
      essay examines the ideological allegiances of the coauthors of the Introduction.
      In particular, it analyzes the ideological implications of their divergent
      opinions on animal instinct. Different vocational pursuits shaped each man's
      natural history. Spence, a political economist, pursued fact-based science that
      was shorn of references to religion. Kirby, a Tory High Churchman, placed
      revelation at the very heart of his natural history. His strong commitment to
      partisan sectarianism cautions against reference to a homogeneous "natural
      theology" that was an agent of mediation. Fissures in the "common intellectual
      context" reached beyond the clash between natural theologians and radical
      anatomists to render the intellectual edifice of natural theology structurally
      less sound for the future.

PMID- 16640234
TI  - Diversity: What differences make a difference?

PMID- 16640235
TI  - Challenges in the diagnosis & treatment of bipolar depression--Part 1:
      assessment.

PMID- 16640236
TI  - Teens & body art.

PMID- 16640237
TI  - Ethical implications of banning smoking.

PMID- 16640238
TI  - Treating newly sober patients.

PMID- 16640239
TI  - Eating disorders across the life span.
AB  - Clearly, eating disorders appear in both men and women across the entire life
      span. Nurses must be aware of eating disorder issues in populations such as
      children and adolescents, adult men, middle-aged women, and older adults so that
      proper screening and treatment can occur to reduce the consequences of these
      potentially life-threatening illnesses.

PMID- 16640240
TI  - Social support needs of families adopting special needs children.
AB  - A grounded theory begins to explain parental practices in seeking social support.
      Interviews with 20 parents who had adopted children with special needs and 5
      health care providers indicated that parents lacked awareness of available
      resources; preferred informal support systems; sought help only when "failing" to
      solve problems; and perceived that health care providers lacked knowledge of
      adoption issues, family dynamics, and common health issues. Parents preferred
      informal to formal supports, and felt upset when formal supports were judged
      ineffective or non-existent.

PMID- 16640241
TI  - Why rural African-American women who use cocaine mistrust women.
AB  - Little is known about the social networks of rural African-American women who use
      drugs, although the social networks of their urban counterparts have been
      characterized as small, mixed gendered, and distrustful of other women. The
      purpose of this study was to gain insight into the characteristics of the social
      networks of rural African-American women, both users and non-users of drugs.
      Thirty rural women who used cocaine participated in in-depth qualitative
      interviews. Rural women who used drugs gave several reasons for their mistrust of
      other women and tended to have small social networks, which included family
      members and men to the exclusion of non-familial women. The findings of this
      study have implications for both research and practice.

PMID- 16640242
TI  - How to make a better "bad" kid.

PMID- 16640243
TI  - Segmentation of discrete vector fields.
AB  - In this paper, we propose an approach for 2D discrete vector field segmentation
      based on the Green function and normalized cut. The method is inspired by
      discrete Hodge Decomposition such that a discrete vector field can be broken down
      into three simpler components, namely, curl-free, divergence-free, and harmonic
      components. We show that the Green Function Method (GFM) can be used to
      approximate the curl-free and the divergence-free components to achieve our goal
      of the vector field segmentation. The final segmentation curves that represent
      the boundaries of the influence region of singularities are obtained from the
      optimal vector field segmentations. These curves are composed of piecewise smooth
      contours or streamlines. Our method is applicable to both linear and nonlinear
      discrete vector fields. Experiments show that the segmentations obtained using
      our approach essentially agree with human perceptual judgement.

PMID- 16640244
TI  - Interpolation over arbitrary topology meshes using a two-phase subdivision
      scheme.
AB  - The construction of a smooth surface interpolating a mesh of arbitrary
      topological type is an important problem in many graphics applications. This
      paper presents a two-phase process, based on a topological modification of the
      control mesh and a subsequent Catmull-Clark subdivision, to construct a smooth
      surface that interpolates some or all of the vertices of a mesh with arbitrary
      topology. It is also possible to constrain the surface to have specified tangent
      planes at an arbitrary subset of the vertices to be interpolated. The method has
      the following features: 1) It is guaranteed to always work and the computation is
      numerically stable, 2) there is no need to solve a system of linear equations and
      the whole computation complexity is O(K) where K is the number of the vertices,
      and 3) each vertex can be associated with a scalar shape handle for local shape
      control. These features make interpolation using Catmull-Clark surfaces simple
      and, thus, make the new method itself suitable for interactive free-form shape
      design.

PMID- 16640245
TI  - Knowledge discovery in high-dimensional data: case studies and a user survey for
      the rank-by-feature framework.
AB  - Knowledge discovery in high-dimensional data is a challenging enterprise, but new
      visual analytic tools appear to offer users remarkable powers if they are ready
      to learn new concepts and interfaces. Our three-year effort to develop versions
      of the Hierarchical Clustering Explorer (HCE) began with building an interactive
      tool for exploring clustering results. It expanded, based on user needs, to
      include other potent analytic and visualization tools for multivariate data,
      especially the rank-by-feature framework. Our own successes using HCE provided
      some testimonial evidence of its utility, but we felt it necessary to get beyond
      our subjective impressions. This paper presents an evaluation of the Hierarchical
      Clustering Explorer (HCE) using three case studies and an e-mail user survey (n =
      57) to focus on skill acquisition with the novel concepts and interface for the
      rank-by-feature framework. Knowledgeable and motivated users in diverse fields
      provided multiple perspectives that refined our understanding of strengths and
      weaknesses. A user survey confirmed the benefits of HCE, but gave less guidance
      about improvements. Both evaluations suggested improved training methods.

PMID- 16640246
TI  - CAVE and fishtank virtual-reality displays: a qualitative and quantitative
      comparison.
AB  - We present the results from a qualitative and quantitative user study comparing
      fishtank virtual-reality (VR) and CAVE displays. The results of the qualitative
      study show that users preferred the fishtank VR display to the CAVE system for
      our scientific visualization application because of perceived higher resolution,
      brightness and crispness of imagery, and comfort of use. The results of the
      quantitative study show that users performed an abstract visual search task
      significantly more quickly and more accurately on the fishtank VR display system
      than in the CAVE. The same study also showed that visual context had no
      significant effect on task performance for either of the platforms. We suggest
      that fishtank VR displays are more effective than CAVEs for applications in which
      the task occurs outside the user's reference frame, the user views and
      manipulates the virtual world from the outside in, and the size of the virtual
      object that the user interacts with is smaller than the user's body and fits into
      the fishtank VR display. The results of both studies support this proposition.

PMID- 16640247
TI  - Ribbon networks for modeling navigable paths of autonomous agents in virtual
      environments.
AB  - This paper presents the Environment Description Framework (EDF) for modeling
      complex networks of intersecting roads and pathways in virtual environments. EDF
      represents information about the layout of streets and sidewalks, the rules that
      govern behavior on roads and walkways, and the locations of agents with respect
      to navigable structures. The framework serves as the substrate on which behavior
      programs for autonomous vehicles and pedestrians are built. Pathways are modeled
      as ribbons in space. The ribbon structure provides a natural coordinate frame for
      defining the local geometry of navigable surfaces. EDF includes a powerful
      runtime interface supported by robust and efficient code for locating objects on
      the ribbon network, for mapping between Cartesian and ribbon coordinates, and for
      determining behavioral constraints imposed by the environment.

PMID- 16640248
TI  - Melting and burning solids into liquids and gases.
AB  - We propose a novel technique for melting and burning solid materials, including
      the simulation of the resulting liquid and gas. The solid is simulated with
      traditional mesh-based techniques (triangles or tetrahedra) which enable robust
      handling of both deformable and rigid objects, collision and self-collision,
      rolling, friction, stacking, etc. The subsequently created liquid or gas is
      simulated with modern grid-based techniques, including vorticity confinement and
      the particle level set method. The main advantage of our method is that state-of
      the-art techniques are used for both the solid and the fluid without compromising
      simulation quality when coupling them together or converting one into the other.
      For example, we avoid modeling solids as Eulerian grid-based fluids with high
      viscosity or viscoelasticity, which would preclude the handling of thin shells,
      self-collision, rolling, etc. Thus, our method allows one to achieve new effects
      while still using their favorite algorithms (and implementations) for simulating
      both solids and fluids, whereas other coupling algorithms require major algorithm
      and implementation overhauls and still fail to produce rich coupling effects
      (e.g., melting and burning solids).

PMID- 16640249
TI  - Accurate direct illumination using iterative adaptive sampling.
AB  - This paper introduces a new multipass algorithm for efficiently computing direct
      illumination in scenes with many lights and complex occlusion. Images are first
      divided into 8 x 8 pixel blocks and for each point to be shaded within a block, a
      probability density function (PDF) is constructed over the lights and sampled to
      estimate illumination using a small number of shadow rays. Information from these
      samples is then aggregated at both the pixel and block level and used to optimize
      the PDFs for the next pass. Over multiple passes the PDFs and pixel estimates are
      updated until convergence. Using aggregation and feedback progressively improves
      the sampling and automatically exploits both visibility and spatial coherence. We
      also use novel extensions for efficient antialiasing. Our adaptive multipass
      approach computes accurate direct illumination eight times faster than prior
      approaches in tests on several complex scenes.

PMID- 16640250
TI  - Dynamic simulation of articulated rigid bodies with contact and collision.
AB  - We propose a novel approach for dynamically simulating articulated rigid bodies
      undergoing frequent and unpredictable contact and collision. In order to leverage
      existing algorithms for nonconvex bodies, multiple collisions, large contact
      groups, stacking, etc., we use maximal rather than generalized coordinates and
      take an impulse-based approach that allows us to treat articulation, contact, and
      collision in a unified manner. Traditional constraint handling methods are
      subject to drift, and we propose a novel prestabilization method that does not
      require tunable potentially stiff parameters as does Baumgarte stabilization.
      This differs from poststabilization in that we compute allowable trajectories
      before moving the rigid bodies to their new positions, instead of correcting them
      after the fact when it can be difficult to incorporate the effects of contact and
      collision. A poststabilization technique is used for momentum and angular
      momentum. Our approach works with any black box method for specifying valid joint
      constraints and no special considerations are required for arbitrary closed loops
      or branching. Moreover, our implementation is linear both in the number of bodies
      and in the number of auxiliary contact and collision constraints, unlike many
      other methods that are linear in the number of bodies, but not in the number of
      auxiliary constraints.

PMID- 16640251
TI  - Meshless thin-shell simulation based on global conformal parameterization.
AB  - This paper presents a new approach to the physically-based thin-shell simulation
      of point-sampled geometry via explicit, global conformal point-surface
      parameterization and meshless dynamics. The point-based global parameterization
      is founded upon the rigorous mathematics of Riemann surface theory and Hodge
      theory. The parameterization is globally conformal everywhere except for a
      minimum number of zero points. Within our parameterization framework, any well
      sampled point surface is functionally equivalent to a manifold, enabling popular
      and powerful surface-based modeling and physically-based simulation tools to be
      readily adapted for point geometry processing and animation. In addition, we
      propose a meshless surface computational paradigm in which the partial
      differential equations (for dynamic physical simulation) can be applied and
      solved directly over point samples via Moving Least Squares (MLS) shape functions
      defined on the global parametric domain without explicit connectivity
      information. The global conformal parameterization provides a common domain to
      facilitate accurate meshless simulation and efficient discontinuity modeling for
      complex branching cracks. Through our experiments on thin-shell elastic
      deformation and fracture simulation, we demonstrate that our integrative method
      is very natural, and that it has great potential to further broaden the
      application scope of point-sampled geometry in graphics and relevant fields.

PMID- 16640252
TI  - Dual Laplacian editing for meshes.
AB  - Recently, differential information as local intrinsic feature descriptors has
      been used for mesh editing. Given certain user input as constraints, a deformed
      mesh is reconstructed by minimizing the changes in the differential information.
      Since the differential information is encoded in a global coordinate system, it
      must somehow be transformed to fit the orientations of details in the deformed
      surface, otherwise distortion will appear. We observe that visually pleasing
      deformed meshes should preserve both local parameterization and geometry details.
      We propose to encode these two types of information in the dual mesh domain due
      to the simplicity of the neighborhood structure of dual mesh vertices. Both sets
      of information are nondirectional and nonlinearly dependent on the vertex
      positions. Thus, we present a novel editing framework that iteratively updates
      both the primal vertex positions and the dual Laplacian coordinates to
      progressively reduce distortion in parametrization and geometry. Unlike previous
      related work, our method can produce visually pleasing deformations with simple
      user interaction, requiring only the handle positions, not local frames at the
      handles.

PMID- 16640253
TI  - The effect of visual and interaction fidelity on spatial cognition in immersive
      virtual environments.
AB  - Accuracy of memory performance per se is an imperfect reflection of the cognitive
      activity (awareness states) that underlies performance in memory tasks. The aim
      of this research is to investigate the effect of varied visual and interaction
      fidelity of immersive virtual environments on memory awareness states. A between
      groups experiment was carried out to explore the effect of rendering quality on
      location-based recognition memory for objects and associated states of awareness.
      The experimental space, consisting of two interconnected rooms, was rendered
      either flat-shaded or using radiosity rendering. The computer graphics
      simulations were displayed on a stereo head-tracked Head Mounted Display.
      Participants completed a recognition memory task after exposure to the
      experimental space and reported one of four states of awareness following object
      recognition. These reflected the level of visual mental imagery involved during
      retrieval, the familiarity of the recollection, and also included guesses.
      Experimental results revealed variations in the distribution of participants'
      awareness states across conditions while memory performance failed to reveal any.
      Interestingly, results revealed a higher proportion of recollections associated
      with mental imagery in the flat-shaded condition. These findings comply with
      similar effects revealed in two earlier studies summarized here, which
      demonstrated that the less "naturalistic" interaction interface or interface of
      low interaction fidelity provoked a higher proportion of recognitions based on
      visual mental images.

PMID- 16640254
TI  - A network architecture supporting consistent rich behavior in collaborative
      interactive applications.
AB  - Network architectures for collaborative virtual reality have traditionally been
      dominated by client-server and peer-to-peer approaches, with peer-to-peer
      strategies typically being favored where minimizing latency is a priority, and
      client-server where consistency is key. With increasingly sophisticated behavior
      models and the demand for better support for haptics, we argue that neither
      approach provides sufficient support for these scenarios and, thus, a hybrid
      architecture is required. We discuss the relative performance of different
      distribution strategies in the face of real network conditions and illustrate the
      problems they face. Finally, we present an architecture that successfully meets
      many of these challenges and demonstrate its use in a distributed virtual
      prototyping application which supports simultaneous collaboration for assembly,
      maintenance, and training applications utilizing haptics.

PMID- 16640255
TI  - Morphological image compositing.
AB  - Image mosaicking can be defined as the registration of two or more images that
      are then combined into a single image. Once the images have been registered to a
      common coordinate system, the problem amounts to the definition of a selection
      rule to output a unique value for all those pixels that are present in more than
      one image. This process is known as image compositing. In this paper, we propose
      a compositing procedure based on mathematical morphology and its marker
      controlled segmentation paradigm. Its scope is to position seams along salient
      image structures so as to diminish their visibility in the output mosaic even in
      the absence of radiometric corrections or blending procedures. We also show that
      it is suited to the seamless minimization of undesirable transient objects
      occurring in the regions where two or more images overlap. The proposed
      methodology and algorithms are illustrated for the composition of satellite
      images minimizing cloud cover.

PMID- 16640256
TI  - Component optimization for image understanding: a Bayesian approach.
AB  - In this paper, the optimizations of three fundamental components of image
      understanding: segmentation/annotation, 3D sensing (stereo) and 3D fitting, are
      posed and integrated within a Bayesian framework. This approach benefits from
      recent advances in statistical learning which have resulted in greatly improved
      flexibility and robustness. The first two components produce annotation (region
      labeling) and depth maps for the input images, while the third module integrates
      and resolves the inconsistencies between region labels and depth maps to fit most
      likely 3D models. To illustrate the application of these ideas, we have focused
      on the difficult problem of fitting individual tree models to tree stands which
      is a major challenge for vision-based forestry inventory systems.

PMID- 16640257
TI  - On-road vehicle detection: a review.
AB  - Developing on-board automotive driver assistance systems aiming to alert drivers
      about driving environments, and possible collision with other vehicles has
      attracted a lot of attention lately. In these systems, robust and reliable
      vehicle detection is a critical step. This paper presents a review of recent
      vision-based on-road vehicle detection systems. Our focus is on systems where the
      camera is mounted on the vehicle rather than being fixed such as in
      traffic/driveway monitoring systems. First, we discuss the problem of on-road
      vehicle detection using optical sensors followed by a brief review of intelligent
      vehicle research worldwide. Then, we discuss active and passive sensors to set
      the stage for vision-based vehicle detection. Methods aiming to quickly
      hypothesize the location of vehicles in an image as well as to verify the
      hypothesized locations are reviewed next. Integrating detection with tracking is
      also reviewed to illustrate the benefits of exploiting temporal continuity for
      vehicle detection. Finally, we present a critical overview of the methods
      discussed, we assess their potential for future deployment, and we present
      directions for future research.

PMID- 16640258
TI  - Offline Arabic handwriting recognition: a survey.
AB  - The automatic recognition of text on scanned images has enabled many applications
      such as searching for words in large volumes of documents, automatic sorting of
      postal mail, and convenient editing of previously printed documents. The domain
      of handwriting in the Arabic script presents unique technical challenges and has
      been addressed more recently than other domains. Many different methods have been
      proposed and applied to various types of images. This paper provides a
      comprehensive review of these methods. It is the first survey to focus on Arabic
      handwriting recognition and the first Arabic character recognition survey to
      provide recognition rates and descriptions of test data for the approaches
      discussed. It includes background on the field, discussion of the methods, and
      future research directions.

PMID- 16640259
TI  - Capitalize on dimensionality increasing techniques for improving Face Recognition
      Grand Challenge performance.
AB  - This paper presents a novel pattern recognition framework by capitalizing on
      dimensionality increasing techniques. In particular, the framework integrates
      Gabor image representation, a novel multiclass Kernel Fisher Analysis (KFA)
      method, and fractional power polynomial models for improving pattern recognition
      performance. Gabor image representation, which increases dimensionality by
      incorporating Gabor filters with different scales and orientations, is
      characterized by spatial frequency, spatial locality, and orientational
      selectivity for coping with image variabilities such as illumination variations.
      The KFA method first performs nonlinear mapping from the input space to a high
      dimensional feature space, and then implements the multiclass Fisher discriminant
      analysis in the feature space. The significance of the nonlinear mapping is that
      it increases the discriminating power of the KFA method, which is linear in the
      feature space but nonlinear in the input space. The novelty of the KFA method
      comes from the fact that 1) it extends the two-class kernel Fisher methods by
      addressing multiclass pattern classification problems and 2) it improves upon the
      traditional Generalized Discriminant Analysis (GDA) method by deriving a unique
      solution (compared to the GDA solution, which is not unique). The fractional
      power polynomial models further improve performance of the proposed pattern
      recognition framework. Experiments on face recognition using both the FERET
      database and the FRGC (Face Recognition Grand Challenge) databases show the
      feasibility of the proposed framework. In particular, experimental results using
      the FERET database show that the KFA method performs better than the GDA method
      and the fractional power polynomial models help both the KFA method and the GDA
      method improve their face recognition performance. Experimental results using the
      FRGC databases show that the proposed pattern recognition framework improves face
      recognition performance upon the BEE baseline algorithm and the LDA-based
      baseline algorithm by large margins.

PMID- 16640260
TI  - Meticulously detailed eye region model and its application to analysis of facial
      images.
AB  - We propose a system that is capable of detailed analysis of eye region images in
      terms of the position of the iris, degree of eyelid opening, and the shape,
      complexity, and texture of the eyelids. The system uses a generative eye region
      model that parameterizes the fine structure and motion of an eye. The structure
      parameters represent structural individuality of the eye, including the size and
      color of the iris, the width, boldness, and complexity of the eyelids, the width
      of the bulge below the eye, and the width of the illumination reflection on the
      bulge. The motion parameters represent movement of the eye, including the up-down
      position of the upper and lower eyelids and the 2D position of the iris. The
      system first registers the eye model to the input in a particular frame and
      individualizes it by adjusting the structure parameters. The system then tracks
      motion of the eye by estimating the motion parameters across the entire image
      sequence. Combined with image stabilization to compensate for appearance changes
      due to head motion, the system achieves accurate registration and motion recovery
      of eyes.

PMID- 16640261
TI  - A field model for human detection and tracking.
AB  - The large shape variability and partial occlusions challenge most object
      detection and tracking methods for nonrigid targets such as pedestrians. This
      paper presents a new approach based on a two-layer statistical field model that
      characterizes the prior of the complex shape variations as a Boltzmann
      distribution and embeds this prior and the complex image likelihood into a Markov
      field. A probabilistic variational analysis of this model reveals a set of fixed
      point equations characterizing the equilibrium of the field. It leads to
      computationally efficient methods for calculating the image likelihood and for
      training the model. Based on that, effective algorithms for detecting nonrigid
      objects are developed. This new approach has several advantages. First, it is
      intrinsically suitable for capturing local nonrigidity. In addition, due to the
      distributed likelihood, this approach is robust to partial occlusions. Moreover,
      the two-layer structure provides large flexibility of modeling the image
      observations, which makes the new method robust to clutters. Extensive
      experiments demonstrate its effectiveness.

PMID- 16640262
TI  - Nonparametric supervised learning by linear interpolation with maximum entropy.
AB  - Nonparametric neighborhood methods for learning entail estimation of class
      conditional probabilities based on relative frequencies of samples that are "near
      neighbors" of a test point. We propose and explore the behavior of a learning
      algorithm that uses linear interpolation and the principle of maximum entropy
      (LIME). We consider some theoretical properties of the LIME algorithm: LIME
      weights have exponential form; the estimates are consistent; and the estimates
      are robust to additive noise. In relation to bias reduction, we show that near
      neighbors contain a test point in their convex hull asymptotically. The common
      linear interpolation solution used for regression on grids or look-up-tables is
      shown to solve a related maximum entropy problem. LIME simulation results support
      use of the method, and performance on a pipeline integrity classification problem
      demonstrates that the proposed algorithm has practical value.

PMID- 16640263
TI  - Joint multiregion segmentation and parametric estimation of image motion by basis
      function representation and level set evolution.
AB  - The purpose of this study is to investigate a variational method for joint
      segmentation and parametric estimation of image motion by basis function
      representation of motion and level set evolution. The functional contains three
      terms. One term is of classic regularization to bias the solution toward a
      segmentation with smooth boundaries. A second term biases the solution toward a
      segmentation with boundaries which coincide with motion discontinuities,
      following a description of motion discontinuities by a function of the image
      spatio-temporal variations. The third term refers to region information and
      measures conformity of the parametric representation of the motion of each region
      of segmentation to the image spatio-temporal variations. The components of motion
      in each region of segmentation are represented as functions in a space generated
      by a set of basis functions. The coefficients of the motion components considered
      combinations of the basis functions are the parameters of representation. The
      necessary conditions for a minimum of the functional, which are derived taking
      into consideration the dependence of the motion parameters on segmentation, lead
      to an algorithm which condenses to concurrent curve evolution, implemented via
      level sets, and estimation of the parameters by least squares within each region
      of segmentation. The algorithm and its implementation are verified on synthetic
      and real images using a basis of cosine transforms.

PMID- 16640264
TI  - Multisensor image registration via implicit similarity.
AB  - This paper presents an approach to the registration of significantly dissimilar
      images, acquired by sensors of different modalities. A robust matching criterion
      is derived by aligning the locations of gradient maxima. The alignment is
      achieved by iteratively maximizing the magnitudes of the intensity gradients of a
      set of pixels in one of the images, where the set is initialized by the gradient
      maxima locations of the second image. No explicit similarity measure that uses
      the intensities of both images is used. The computation utilizes the full spatial
      information of the first image and the accuracy and robustness of the
      registration depend only on it. False matchings are detected and adaptively
      weighted using a directional similarity measure. By embedding the scheme in a
      "coarse to fine" formulation, we were able to estimate affine and projective
      global motions, even when the images were characterized by complex space varying
      intensity transformations. The scheme is especially suitable when one of the
      images is of considerably better quality than the other (noise, blur, etc.). We
      demonstrate these properties via experiments on real multisensor image sets.

PMID- 16640265
TI  - A coherent computational approach to model bottom-up visual attention.
AB  - Visual attention is a mechanism which filters out redundant visual information
      and detects the most relevant parts of our visual field. Automatic determination
      of the most visually relevant areas would be useful in many applications such as
      image and video coding, watermarking, video browsing, and quality assessment.
      Many research groups are currently investigating computational modeling of the
      visual attention system. The first published computational models have been based
      on some basic and well-understood Human Visual System (HVS) properties. These
      models feature a single perceptual layer that simulates only one aspect of the
      visual system. More recent models integrate complex features of the HVS and
      simulate hierarchical perceptual representation of the visual input. The bottom
      up mechanism is the most occurring feature found in modern models. This mechanism
      refers to involuntary attention (i.e., salient spatial visual features that
      effortlessly or involuntary attract our attention). This paper presents a
      coherent computational approach to the modeling of the bottom-up visual
      attention. This model is mainly based on the current understanding of the HVS
      behavior. Contrast sensitivity functions, perceptual decomposition, visual
      masking, and center-surround interactions are some of the features implemented in
      this model. The performances of this algorithm are assessed by using natural
      images and experimental measurements from an eye-tracking system. Two adequate
      well-known metrics (correlation coefficient and Kullbacl-Leibler divergence) are
      used to validate this model. A further metric is also defined. The results from
      this model are finally compared to those from a reference bottom-up model.

PMID- 16640266
TI  - Offline grammar-based recognition of handwritten sentences.
AB  - This paper proposes a sequential coupling of a Hidden Markov Model (HMM)
      recognizer for offline handwritten English sentences with a probabilistic bottom
      up chart parser using Stochastic Context-Free Grammars (SCFG) extracted from a
      text corpus. Based on extensive experiments, we conclude that syntax analysis
      helps to improve recognition rates significantly.

PMID- 16640267
TI  - The principal components of natural images revisited.
AB  - This paper investigates the principal components (PCs) of natural gray and color
      images. A horizontal and vertical typology of PCs is found which leads to the
      identification of groups of basis functions for steerable bandpass filters. Using
      this system, the contribution of spatio-chromatic structure to the total variance
      can be quantified for selected spatial frequencies.

PMID- 16640268
TI  - Building k-connected neighborhood graphs for isometric data embedding.
AB  - Isometric data embedding using geodesic distance requires the construction of a
      connected neighborhood graph so that the geodesic distance between every pair of
      data points can be estimated. This paper proposes an approach for constructing k
      connected neighborhood graphs. The approach works by applying a greedy algorithm
      to add each edge, in a nondecreasing order of edge length, to a neighborhood
      graph if end vertices of the edge are not yet k-connected on the graph. The k
      connectedness between vertices is tested using a network flow technique by
      assigning every vertex a unit flow capacity. This approach is applicable to a
      wide range of data. Experiments show that it gives better estimation of geodesic
      distances than other approaches, especially when the data are undersampled or
      nonuniformly distributed.

PMID- 16640269
TI  - Video repairing under variable illumination using cyclic motions.
AB  - This paper presents a complete system capable of synthesizing a large number of
      pixels that are missing due to occlusion or damage in an uncalibrated input
      video. These missing pixels may correspond to the static background or cyclic
      motions of the captured scene. Our system employs user-assisted video layer
      segmentation, while the main processing in video repair is fully automatic. The
      input video is first decomposed into the color and illumination videos. The
      necessary temporal consistency is maintained by tensor voting in the spatio
      temporal domain. Missing colors and illumination of the background are
      synthesized by applying image repairing. Finally, the occluded motions are
      inferred by spatio-temporal alignment of collected samples at multiple scales. We
      experimented on our system with some difficult examples with variable
      illumination, where the capturing camera can be stationary or in motion.

PMID- 16640270
TI  - Single-view-point omnidirectional catadioptric cone mirror imager.
AB  - We present here a comprehensive imaging theory about cone mirrors in a single
      view-point (SVP) configuration and show that an SVP cone mirror catadioptric
      system is not only practical but also has unique advantages for certain
      applications. We show its merits and weaknesses and how to build a workable
      system.

PMID- 16640271
TI  - Comments on "fundamental limits of reconstruction-based superresolution
      algorithms under local translation".
AB  - Fundamental limits of reconstruction-based superresolution were proposed in [1].
      In this note, we point out that their proof is incomplete.

PMID- 16640272
TI  - Noteworthy products at HIMSS.

PMID- 16640273
TI  - An industry in flux: capitalize on change to enhance performance. Interview by
      Robert Neil.

PMID- 16640274
TI  - When seconds count.

PMID- 16640275
TI  - Costly issues of an uncommunicative OR.

PMID- 16640276
TI  - At the heart of savings.

PMID- 16640277
TI  - Making rounds via remote robot.

PMID- 16640278
TI  - Implementing controls in the OR can help reduce cost and inventory.

PMID- 16640279
TI  - Development and validation of a new high-performance liquid chromatography method
      for the determination of gliclazide and repaglinide in pharmaceutical
      formulations.
AB  - A new high-performance liquid chromatography method was developed and validated
      for the quantitation of gliclazide and repaglinide in pharmaceutical
      formulations. Determination was performed using a LiChroCART RP-18 column, a
      mobile phase containing acetonitrile-phosphate buffer (pH 2.1; 60 + 40, v/v), and
      ultraviolet (UV) detection at 225 nm. Repaglinide was used as an internal
      standard for gliclazide determination and gliclazide for repaglinide assay. The
      method was validated with respect to linearity, precision, robustness,
      ruggedness, accuracy, and specificity. The calibration graphs ranged from 0.015
      to 0.09 mg/mL for gliclazide and 0.06 to 0.36 mg/mL for repaglinide. Intra- and
      interday relative standard deviation values for the standard solutions were 0.70
      and 1.01% for gliclazide and 0.78 and 0.93% for repaglinide, respectively. Total
      recoveries of gliclazide and repaglinide from the laboratory-prepared mixtures
      were 99.82 +/- 0.58 and 101.50 +/- 0.46% for gliclazide and repaglinide,
      respectively [mean +/- standard deviation (SD)]. In forced degradation studies,
      the effect of acid, base, oxidation, UV light, and temperature on both drugs was
      also investigated. Finally, the method was applied for the quality control of
      commercial gliclazide and repaglinide tablets. Total recovery was 100.40 +/- 0.35
      and 104.46 +/- 0.23% for gliclazide and repaglinide, respectively (mean +/- SD).

PMID- 16640280
TI  - Spectrophotometric analysis of selective serotonin reuptake inhibitors based on
      formation of charge-transfer complexes with tetracyanoquinodimethane and
      chloranilic acid.
AB  - A simple, accurate, and sensitive spectrophotometric method for analysis of
      selective serotonin reuptake inhibitors (SSRIs) has been developed and validated.
      The analysis was based on the formation of colored charge-transfer complexes
      between the intact molecule of SSRI drug as an n-electron donor and each of
      tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (pCA) as electron
      acceptors. The formed complexes were measured spectrophotometrically at 842 and
      520 nm for TCNQ and pCA, respectively. Different variables and parameters
      affecting the reactions were studied and optimized. Under the optimum reaction
      conditions, linear relationships with good correlation coefficients (0.9975
      0.9996) were found between the absorbances and the concentrations of the
      investigated drugs in the concentration ranges of 4-50 and 20-400 microg/mL with
      TCNQ and pCA, respectively. With all the investigated drugs, TCNQ gave more
      sensitive assays than pCA; the limits of assay detection were 2.5-4.8 and 20-40
      microg/mL with TCNQ and pCA, respectively. The intra- and interassay precisions
      were satisfactory; the relative standard deviations did not exceed 2%. The
      proposed procedures were successfully applied to the analysis of the studied
      drugs in pure form and pharmaceutical formulations with good accuracy; the
      recovery values were 98.4-102.8 +/- 1.24-1.81%. The results obtained from the
      proposed method were statistically comparable with those obtained from the
      previously reported methods.

PMID- 16640281
TI  - Generic nonextractive spectrophotometric method for determination of 4-quinolone
      antibiotics by formation of ion-pair complexes with beta-naphthol.
AB  - This paper describes the development of a generic spontaneous nonextractive
      spectrophotometric method for determination of 13 pharmaceutically important 4
      quinolone antibiotics. The method was based on the formation of yellow-colored
      water-soluble ion-pair complexes between 2% (w/v) beta-naphthol reagent and each
      of the studied drugs in sulfuric acid medium at room temperature. The formed ion
      pair chromogens have maximum absorption peaks in the range of 365-391 nm. The
      concentrations of the reagents and the experimental conditions affecting the
      reaction were optimized. Under the optimum conditions, linear relationships with
      good linear coefficients (0.9987-0.9995) were found between the absorbance and
      concentration of the investigated drugs in the range of 10-350 microg/mL. The
      assay limits of detection and quantitation were 1-9.9 and 3.4-32.9 microg/mL,
      respectively. The precision of the method was satisfactory; the values of
      relative standard deviations did not exceed 2%. The proposed method was
      successfully applied to the analysis of the investigated drugs in pure and
      pharmaceutical dosage forms with good accuracy and precision; the percentages of
      label claim ranged from 97.8-102.8 +/- 0.35-1.60%. The results obtained by the
      proposed spectrophotometric method were comparable with those obtained by the
      official or reported methods. The proposed method is superior to all the
      previously reported ion-pair formation-based methods in terms of simplicity
      because it did not involve extraction procedures for the ion-pair complex.
      Therefore, this method might be recommended for routine use in quality control
      laboratories for analysis of the investigated 4-quinolone antibiotics in their
      pure forms, as well as in pharmaceutical dosage forms.

PMID- 16640282
TI  - Application of inorganic oxidants to the spectrophotometric determination of
      ribavirin in bulk and capsules.
AB  - Eight spectrophotometric methods for determination of ribavirin have been
      developed and validated. These methods were based on the oxidation of the drug by
      different inorganic oxidants: ceric ammonium sulfate, potassium permanganate,
      ammonium molybdate, ammonium metavanidate, chromium trioxide, potassium
      dichromate, potassium iodate, and potassium periodate. The oxidation reactions
      were performed in perchloric acid medium for ceric ammonium sulfate and in
      sulfuric acid medium for the other reagents. With ceric ammonium sulfate and
      potassium permanganate, the concentration of ribavirin in its samples was
      determined by measuring the decrease in the absorption intensity of the colored
      reagents at 315 and 525 nm, respectively. With the other reagents, the
      concentration of ribavirin was determined by measuring the intensity of the
      developed colored reaction products at the wavelengths of maximum absorbance:
      675, 780, 595, 595, 475, and 475 nm for reactions with ammonium molybdate,
      ammonium metavanidate, chromium trioxide, potassium dichromate, potassium iodate,
      and potassium periodate, respectively. Different variables affecting the reaction
      conditions were carefully studied and optimized. Under the optimum conditions,
      linear relationships with good correlation coefficients (0.9984-0.9998) were
      found between the absorbance readings and the concentrations of ribavirin in the
      range of 4-1400 microg/mL. The molar absorptivities were correlated with the
      oxidation potential of the oxidants used. The precision of the methods were
      satisfactory; the values of relative standard deviation did not exceed 1.64%. The
      proposed methods were successfully applied to the analysis of ribavirin in pure
      drug material and capsules with good accuracy and precision; the recovery values
      were 99.2-101.2 +/- 0.48-1.30%. The results obtained using the proposed
      spectrophotometric methods were comparable with those obtained with the official
      method stated in the United States Pharmacopeia.

PMID- 16640283
TI  - Reversed-phase high-performance liquid chromatography determination of selected
      phenolic acids in propolis concentrates in terms of standardization for drug
      manufacturing purposes.
AB  - A reversed-phase high-performance liquid chromatography method with gradient
      elution was developed for the determination of the caffeic, p-coumaric, and
      ferulic acids in propolis concentrates. Solid-phase extraction on an RP18 column
      was applied for preliminary purification, and chromatographic separation was
      performed on 100 RP18e Lichrospher column of particle size 5 microm. The mobile
      phase was obtained by mixing in appropriate ratios 0.03 mM NaH2PO4, acidified
      with H3PO4 up to pH = 3.0, with acetonitrile to obtain a gradient in the elution
      process. Spectrophotometric detection was conducted at 320 nm. Under the
      established conditions, the method featured high sensitivity, good precision, and
      comparability of results, as proven by method validation and statistical analysis
      of the obtained results. The limits of detection were 0.315, 0.325, and 0.695
      microg/mL for caffeic, p-coumaric, and ferulic acids, respectively. The
      corresponding recovery values were 98.14, 101.05, and 99.42% and the linearity
      ranges from 1.31 to 99.18 microg/mL, 1.52 to 119.16 microg/mL, and 2.42 to 184.14
      microg/mL. The precision of the method was expresed by relative standard
      deviation values that did not exceed 3%. It was also shown that the propolis
      concentrates under examination had similar antibacterial activity against
      Staphylococcus aureus ranging from 119.8 to 124.3 microg/mL, contrary to model
      mixtures that showed no antibacterial activity.

PMID- 16640284
TI  - Determination of amlodipine in pharmaceutical dosage forms by liquid
      chromatography and ultraviolet spectrophotometry.
AB  - A liquid chromatography (LC) method and an ultraviolet (UV) spectrophotometric
      method were developed and validated for quantitative determination of amlodipine
      in tablets and compounded capsules. The isocratic LC analyses were performed on
      an RP18 column using a mobile phase composed of 0.1% (v/v) ortho-phosphoric acid
      (pH 3.0) -acetonitrile (60 + 40, v/v) at a flow rate of 1.0 mL/min. The UV
      spectrophotometric method was performed at 238 nm. The analytical methods were
      validated according to International Conference on Harmonization Guidelines. The
      calibration graphs were linear [correlation coefficient (r) > 0.999] in the
      studied concentration range of 10-30 microg/mL for LC and 10-35 microg/mL for UV
      spectrophotometry. The relative standard deviation values for intraday and
      interday precision studies were less than 2%, and the accuracy was greater than
      98% for both methods. The specificity of the LC method was proved using forced
      degradation. Statistical analyses showed no significant difference between the
      results obtained by the 2 methods. The proposed methods are precise and accurate
      and can be applied directly and easily to the oral pharmaceutical preparations of
      amlodipine.

PMID- 16640285
TI  - Subcritical water extraction and determination of nifedipine in pharmaceutical
      formulations.
AB  - A rapid and simple continuous method for the extraction of nifedipine from
      tablets was developed by using pressurized hot water at 150 degrees C. This is
      the first time that subcritical water was applied to the extraction of low
      polarity compounds in pharmaceutical analysis. The method is based on the
      increment in solubility of nifedipine in subcritical water. Extraction
      temperature and static and dynamic extraction time were optimized in order to
      reach quantitative extraction of the drug from the tablets. After extraction, the
      drug was determined by spectrophotometry by measuring absorbance at 338 nm.
      Accuracy and precision of the method were determined by analysis of 10 synthetic
      samples of pharmaceutical formulations prepared with common tablet excipients.
      Recovery was found to be 99.2% with a relative standard deviation of 1.9%, which
      indicates that the excipients of the formulation do not interfere in the
      determination. The method was applied to the determination of the drug content
      uniformity in tablets.

PMID- 16640286
TI  - Determination of chloramphenicol residue in chicken tissues by immunoaffinity
      chromatography cleanup and gas chromatography with a microcell electron capture
      detector.
AB  - A rapid and sensitive gas chromatography (GC) method was developed to detect
      chloramphenicol in chicken tissues. The extracted samples were cleaned up using
      the immunoaffinity column prepared by coupling antichloramphenicol monoclonal
      antibody with cyanogen bromide-activated Sepharose 4B. The dynamic column
      capacity of chloramphenicol was 3265 ng/mL gel. The eluate was evaporated to
      dryness, and residues were derivatized and determined by GC with a microcell
      electron capture detector. Average recoveries were 86.6 to 96.9% for chicken
      muscle and 74.3 to 96.1% for chicken liver. The limit of quantitation of the
      method was 0.05 ng/g for chicken muscle and 0.1 ng/g for chicken liver.

PMID- 16640287
TI  - Roche/BIOTECON Diagnostics LightCycler foodproof L. monocytogenes detection kit
      in combination with ShortPrep foodproof II Kit. Performance-Tested Method 070401.
AB  - A method was developed for the detection of L. monocytogenes in food based on
      real-time polymerase chain reaction (PCR). This advanced PCR method was designed
      to reduce the time needed to achieve results from PCR reactions and to enable the
      user to monitor the amplification of the PCR product simultaneously, in real
      time. After DNA isolation using the Roche/BIOTECON Diagnostics ShortPrep
      foodproof II Kit (formerly called Listeria ShortPrep Kit) designed for the rapid
      preparation of L. monocytogenes DNA for direct use in PCR, the real-time
      detection of L. monocytogenes DNA is performed by using the Roche/BIOTECON
      Diagnostics LightCycler foodproof L. monocytogenes Detection Kit. This kit
      provides primers and hybridization probes for sequence-specific detection,
      convenient premixed reagents, and different controls for reliable interpretation
      of results. For repeatability studies, 20 different foods, covering the 15 food
      groups recommended from the AOAC Research Institute (AOAC RI) for L.
      monocytogenes detection were analyzed: raw meats, fresh produce/vegetables,
      processed meats, seafood, egg and egg products, dairy (cultured/noncultured),
      spices, dry foods, fruit/juices, uncooked pasta, nuts, confectionery, pet food,
      food dyes and colorings, and miscellaneous. From each food 20, samples were
      inoculated with a low level (1-10 colony-forming units (CFU)/25 g) and 20 samples
      with a high level (10-50 CFU/25 g) of L. monocytogenes. Additionally, 5
      uninoculated samples were prepared from each food. The food samples were examined
      with the test kits and in correlation with the cultural methods according to U.S.
      Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) or
      U.S. Department of Agriculture (USDA)/Food Safety and Inspection Service (FSIS)
      Microbiology Laboratory Guidebook. After 48 h of incubation, the PCR method in
      all cases showed equal or better results than the reference cultural FDA/BAM or
      USDA/FSIS methods. Fifteen out of 20 tested food types gave exactly the same
      amount of positive samples for both methods in both inoculation levels. For 5 out
      of 20 foodstuffs, the PCR method resulted in more positives than the reference
      method after 48 h of incubation. Following AOAC RI definition, these were false
      positives because they were not confirmed by the reference method (false-positive
      rate for low inoculated foodstuffs: 5.4%; for high inoculated foodstuffs: 7.1%).
      Without calculating these unconfirmed positives, the PCR method showed equal
      sensitivity results compared to the alternative method. With the unconfirmed PCR
      positives included into the calculations, the alternative PCR method showed a
      higher sensitivity than the microbiological methods (low inoculation level: 100
      vs 98.0%; sensitivity rate: 1; high inoculation level: 99.7 vs 97.7%; sensitivity
      rate, 1). All in-house and independently tested uninoculated food samples were
      negative for L. monocytogenes. The ruggedness testing of both ShortPrep foodproof
      II Kit and Roche/BIOTECON LightCycler foodproof L. monocytogenes Detection Kit
      showed no noteworthy influences to any variation of the parameters component
      concentration, apparatus comparison, tester comparison, and sample volumes. In
      total, 102 L. monocytogenes isolates (cultures and pure DNA) were tested and
      detected for the inclusivity study, including all isolates claimed by the AOAC
      RI. The exclusivity study included 60 non-L. monocytogenes bacteria. None of the
      tested isolates gave a false-positive result; specificity was 100%. Three
      different lots were tested in the lot-to-lot study. All 3 lots gave equal
      results. The stability study was subdivided into 3 parts: long-term study, stress
      test, and freeze-defrost test. Three lots were tested in 4 time intervals within
      a period of 13 months. They all gave comparable results for all test intervals.
      For the stress test, LightCycler L. monocytogenes detection mixes were stored at
      different temperatures and tested at different time points during 1 month. Stable
      results were produced at all storage temperatures. The freeze-defrost analysis
      showed no noteworthy aggravation of test results. The independent validation
      study examined by Campden and Chorleywood Food Research Association Group (CCFRA)
      demonstrated again that the LightCycler L. monocytogenes detection system shows a
      comparable sensitivity to reference methods. With both the LightCycler PCR and
      BAM methods, 19 out of 20 inoculated food samples were detected. The 24 h PCR
      results generated by the LightCycler system corresponded directly with the
      FDA/BAM culture results. However, the 48 h PCR results did not relate exactly to
      the FDA/BAM results, as one sample found to be positive by the 48 h PCR could not
      be culturally confirmed and another sample which was negative by the 48 h PCR was
      culturally positive.

PMID- 16640288
TI  - Evaluation of the Sanita-kun coliforms, a dehydrated medium sheet for coliform
      detection. Performance-Tested Method 100402.
AB  - The Sanita-kun Coliforms consists of a transparent cover film, an adhesive sheet,
      a layer of nonwoven fabric, and a water-soluble compound film, including a
      culture medium formula for the detection of coliforms. The medium sheet was
      validated with 26 food types belonging to 9 food categories (meat, poultry, fish
      and seafood, fruits and vegetable, dairy, chocolate or bakery, animal feeds,
      pasta, and miscellaneous) using violet red bile (VRB) agar method in the U.S.
      Food and Drug Administration's Bacteriological Analytical Manual as a reference
      according to the AOAC guideline. The medium sheet showed 100% inclusivity and
      exclusivity. Ruggedness study suggested allowances in the incubation temperature
      and time as 33-35 degrees C and 24 +/- 4 h, respectively. The performance of 3
      different lots of the medium sheets was equivalent and suggested no change of the
      performance at least for 3 years. In the comparative recovery study, many samples
      (84.6%), which were inoculated with a coliform strain, showed no significant
      difference between the 2 methods. The linear correlation coefficient (r2) to the
      VRB agar was calculated as 0.94. In the repeatability study, the average relative
      standard deviation of total foods was 0.10 in the medium sheet. In the
      independent study, the medium sheet detected significantly more colonies than VRB
      plates in the frozen raw milk sample, while there was no significant difference
      between the 2 methods in raw ground beef sample. Comparative recovery study on
      foods, inoculated and then frozen, showed the medium sheet detected injured cells
      with better recovery than VRB agar. The analysts in the independent study wrote
      that the medium sheet was easy to use and read overall. The Sanita-kun sheet
      provides an alternative method to coliform count agar.

PMID- 16640289
TI  - Singlepath Salmonella. Performance-Tested Method 060401.
AB  - Singlepath Salmonella is an immunochromatographic (lateral flow) assay for the
      presumptive qualitative detection of Salmonella spp. in food. The AOAC
      Performance-Tested Method study evaluated Singlepath Salmonella as an effective
      method for the detection of Salmonella spp. in the following selected foods:
      dried skimmed milk, black pepper, dried pet food, desiccated coconut, cooked
      peeled frozen prawns, raw ground beef, and raw ground turkey. When the foods were
      inoculated with Salmonella spp. at levels ranging from low [0.23-1.08 colony
      forming units (CFU)/25 g] to high (2.3-6.0 CFU/25 g), a Chi-square value of 0.9
      indicated that there was no significant difference between Singlepath Salmonella
      and the ISO 6579:2002 reference method. Singlepath Salmonella gave a false
      positive rate of 7.3% and a false-negative rate of 2.5%. For the inclusivity
      study, all 105 Salmonella serovars reacted with Singlepath Salmonella. For the
      exclusivity study, 58 non-Salmonella spp. were tested. There were no cross
      reactions with Singlepath Salmonella from these strains.

PMID- 16640290
TI  - Predicting aflatoxin and fumonisin in shelled corn lots using poor-quality grade
      components.
AB  - A study was conducted to determine if aflatoxin and fumonisin are concentrated in
      the poor-quality grade components of shelled corn. Four 1.0 kg test samples were
      each taken from 23 lots of shelled corn marketed in North Carolina. Inspectors
      from the Federal Grain Inspection Service divided each test sample into 3 grade
      components: (1) damaged kernels (DM), (2) broken corn and foreign material
      (BCFM), and )3) whole kernels (WH). The aflatoxin and fumonisin concentration was
      measured in each component and a mass balance equation was used to calculate the
      total concentration of each mycotoxin in each test sample. Averaged across all
      test samples, the aflatoxin concentrations in the DM, BCFM, and WH components
      were 1300.3, 455.2, and 37.3 ppb, respectively. Averaged across all test samples,
      the fumonisin concentrations in the DM, BCFM, and WH components were 148.3, 51.3,
      and 1.8 ppm, respectively. The DM and BCFM components combined accounted for only
      5.0% of the test sample mass, but accounted for 59.8 and 77.5% of the total
      aflatoxin and fumonisin mass in the test sample, respectively. Both aflatoxin
      mass (ng) and aflatoxin concentration (ng/g) in the combined DM and BCFM
      components had high correlations with aflatoxin concentration in the lot. The
      highest correlation occurred when aflatoxin mass (ng) in the combined DM and BCFM
      components was related to aflatoxin concentration in the lot (0.964). Similar
      results were obtained for fumonisin. This study indicated that measuring either
      aflatoxin or fumonisin in the combined DM and BCFM grade components could be used
      as a screening method to predict either aflatoxin or fumonisin in a bulk lot of
      shelled corn.

PMID- 16640291
TI  - Sterol oxidation in meat- and fish-based homogenized baby foods containing
      vegetable oils.
AB  - Sterol oxidation was evaluated in commercial meat- and fish-based homogenized
      baby foods containing vegetable oil. Gas chromatography coupled with mass
      spectrometry (GC/MS) was used for the analytical determination of 7
      ketocholesterol and 7-ketositosterol, which were chosen as markers of sterol
      oxidation in lipids of animal origin and vegetable origin, respectively.
      Cholestanetriol was also quantified, because its negative effects on
      atherogenesis and other biological processes are well known. In meat-based
      samples, the levels of 7-ketocholesterol and 7-ketositosterol were 22-89 and 11
      40 microg/serving, respectively, whereas the cholestanetriol levels were 7-38
      microg/serving. The 7-ketocholesterol/cholesterol percent ratio was
      characteristic of each kind of meat and related to the levels of unsaturated
      fatty acids of animal lipids. In fish-based samples, the cholestanetriol and 7
      ketocholesterol levels per serving were significantly lower than in meat samples,
      but in fish fillets they were about 20-25%, instead of 40%, of the ingredients.
      The values of the 7-ketocholesterol/cholesterol percent ratio in fish-based
      products were close to the values computed for chicken or turkey-based products.
      The detected values of cholestanetriol showed that the addition of vegetable oil
      enhances the development of the indirect bimolecular pathway of cholesterol
      oxidation, which was even more favorable in fish-based products.

PMID- 16640292
TI  - Use of Griess reagent containing vanadium(III) for post-column derivatization and
      simultaneous determination of nitrite and nitrate in baby food.
AB  - An ion chromatographic method with post-column derivatization and
      spectrophotometric detection is presented for the determination of nitrate and
      nitrite (NOx) in baby food. NOx residues found naturally or added as
      preservatives were extracted from baby foods and determined by using ion
      chromatography with post-column derivatization and spectrophotometric detection.
      Nitrate was reduced to nitrite online by post-column reduction using
      vanadium(lll) chloride and heat. Nitrite reacted with Griess reagent to produce a
      dye that was detected at 525 nm. The use of V(III) and heat to promote the
      reduction of nitrate to nitrite online is a novel feature of this detection
      system. The determination of incurred NOx residues in samples by using AOAC
      Method 993.03 yielded results comparable to those obtained by ion chromatography
      with spectrophotometric detection. The toxic and carcinogenic metal cadmium used
      in the AOAC Method to reduce the nitrate to nitrite was avoided. The proposed
      method provides simultaneous determination of nitrate and nitrite. Average
      recoveries of nitrate and nitrite residues ranged from 82 to 107% for
      fortification levels of 25-400 ppm.

PMID- 16640293
TI  - Influence of white reference measurement and background on the color
      specification of orange juices by means of diffuse reflectance spectrophotometry.
AB  - The color of citrus beverages, in general, is related to the consumers'
      perception of flavor, sweetness, and other characteristics related to the quality
      of these products, so it is important to develop suitable methods for accurately
      assessing this attribute. In this study, the color of 2 different kinds of orange
      juices (ultrafrozen orange juices and orange juices from concentrate) were
      measured using different white references in order to demonstrate the influence
      of white reference measurement on the color parameters obtained. The results of
      this work indicated that the election of a wrong white reference measurement can
      affect dramatically the accuracy of the objective specification of orange juice
      color. Thus, the application of analysis of variance (alpha = 0.01) revealed
      that, in most cases, the parameters obtained were significantly different. In
      terms of color differences, the change of the background for the same white
      reference affected the measurements less than the changes of white references for
      the same background. On the other hand, important chromatic differences between
      the 2 types of orange juices studied were found.

PMID- 16640294
TI  - Determination of magnesium stearate in capsule- or tablet-type supplements.
AB  - A simple method for the determination of magnesium stearate in capsule- or tablet
      type supplements was developed. Free stearic acid in the sample was removed by
      extraction with tetrahydrofuran. The remaining stearate was converted to stearic
      acid by reaction with a cation-exchange resin. The resulting stearic acid was
      determined by gas chromatography with a polar column. Esters of stearic acid were
      not converted to stearic acid and would not cause a positive error in the amount
      of stearate. The amount of magnesium stearate was calculated based on the stearic
      acid concentration thus obtained. Magnesium stearate levels in 5 out of 25
      supplements exceeded 2500 microg/g, which indicated the possible admixture of
      magnesium stearate.

PMID- 16640295
TI  - Validation of two commercial lateral flow devices for the detection of peanut
      proteins in cookies: interlaboratory study.
AB  - Results are reported for an interlaboratory validation study of 2 commercially
      available Iateral flow devices (dipstick tests) designed to detect peanut
      residues in food matrixes. The test samples used in this study were cookies
      containing peanuts at 7 different concentrations in the range of 0-30 mg
      peanuts/kg food matrix. The test samples with sufficient and proven homogeneity
      were prepared in our laboratory. The analyses of the samples (5 times per level
      by each laboratory) were performed by 18 laboratories worldwide which submitted a
      total of 1260 analytical results. One laboratory was found to be an outlier for
      one of the test kits. In general, both test kits performed well. However, some
      false-negative results were reported for all matrixes containing < 21 mg
      peanuts/kg cookie. It must be stressed that the test kits were challenged beyond
      their cut-off limits (> or = 5 mg/kg, depending on the food matrix). One test kit
      showed fewer false-negative results, but it led to some false-positive results
      for the blank materials. The sensitivity of the dipstick tests approaches that
      achieved with enzyme-linked immunosorbent assays.

PMID- 16640296
TI  - High-throughput determination of seven trace elements in food samples by
      inductively coupled plasma-mass spectrometry.
AB  - A method was developed for high-throughput determinations of 7 elements in food
      samples, namely antimony (Sb), arsenic (As), cadmium (Cd), chromium (Cr), lead
      (Pb), mercury (Hg), and tin (Sn). The samples were digested by closed-vessel
      microwave-assisted digestion using concentrated nitric acid (HNO3) as the medium,
      followed by microwave- assisted evaporation to concentrate the sample solutions
      before dilution to the desired volume. The microwave-assisted evaporation
      procedure effectively reduced the final acid concentration to around 8% before
      analysis by inductively coupled plasma-mass spectrometry (ICP-MS). This reduction
      allows determination by ICP-MS to proceed without further sample dilution, which
      would affect the detection limit. The method was validated, and method recoveries
      for As, Cd, Cr, Pb, and Hg were within the certified ranges of the chosen
      certified reference materials. Recoveries of the 7 elements from spiked samples
      ranged from 93.1 to 103.6%. The standard uncertainties of precision for the 7
      elements were between 3.1 and 4.3%. Interlaboratory comparison studies for As,
      Cd, and Pb gave z-scores ranging from -0.2 to 0.3.

PMID- 16640297
TI  - Measurements of ambient ozone using indigo blue-coated filters.
AB  - Ozone monitoring techniques utilize expensive instruments that are often large
      and heavy. These instruments are not easy to handle in the field, and their size
      also limits some sampling schemes, principally for indoor ozone determination. We
      have developed a lightweight, inexpensive, and sensitive method that offers
      flexibility to undertake measurements of ambient ozone in many environments, both
      indoor and outdoor. The method is based on the reaction of ozone with indigo blue
      dye. The indigo molecule contains 1 carbon double bond (C = C) that reacts with
      ozone and results in nearly colorless reaction products. During sample
      collection, 2 cellulose filters coated with 40 micro of 1.0 x 10(-3) M indigo
      blue were used. The determinations were done spectrophotometrically at 250 and
      600 nm. The analytical parameters studied were sampling time and flow rate.
      Analytical curves were constructed with concentrations ranging from 37 to 123
      parts per billion by volume (ppbv) of standard ozone, at 0.4 L/min and 15 min
      sampling time. The detection limits achieved were 6 and 9 ppbv, respectively, at
      250 and 600 nm. Considering interferences, measurements made at 250 nm gave more
      reliable and specific values for ozone.

PMID- 16640298
TI  - Method development for the analysis of N-nitrosodimethylamine and other N
      nitrosamines in drinking water at low nanogram/liter concentrations using solid
      phase extraction and gas chromatography with chemical ionization tandem mass
      spectrometry.
AB  - N-nitrosodimethylamine (NDMA) is a probable human carcinogen of concern that has
      been identified as a drinking water contaminant. U.S. Environmental Protection
      Agency Method 521 has been developed for the analysis of NDMA and 6 additional N
      nitrosamines in drinking water at low ng/L concentrations. The method uses solid
      phase extraction with coconut charcoal as the sorbent and dichloromethane as the
      eluent to concentrate 0.50 L water samples to 1 mL. The extracts are analyzed by
      gas chromatography-chemical ionization tandem mass spectrometry using large
      volume injection. Method performance was evaluated in 2 laboratories. Typical
      analyte recoveries of 87-104% were demonstrated for fortified reagent water
      samples, and recoveries of 77-106% were demonstrated for fortified drinking water
      samples. All relative standard deviations on replicate analyses were < 11%.

PMID- 16640299
TI  - Matrix solid-phase dispersion microextraction and determination of pesticide
      residues in medicinal herbs by gas chromatography with a nitrogen-phosphorus
      detector.
AB  - A gas chromatography method for the determination of residues of 6 pesticides in
      Isatis indigotica Fort and Paeonia lactiflora Pall is described. Optimizations of
      different parameters were performed. The method used 0.5 g herb sample, silica
      gel as the matrix solid-phase dispersion sorbent, and acetone as the eluting
      solvent. Recoveries at spiked concentrations between 0.1 and 5 mg/kg were between
      80.63 and 110.12%, with relative standard deviations ranging from 0.43 to 17.67%.
      The limits of quantitation were 0.01 mg/kg for metalaxyl, triadimefon, and
      paclobutrazol and 0.05 mg/kg for vinclozolin, tebuconazole, and fenarimol. The
      method may be useful as a screening protocol for the determination of these
      pesticides in medicinal herb samples.

PMID- 16640300
TI  - Clonal structure and variation in virulence of Salmonella enteritidis isolated
      from mice, chickens, and humans.
AB  - The clonal analysis of a diverse collection of Salmonella Enteritidis indicates
      that most strains belong to a single multilocus genotype (i.e., ET-3) regardless
      of phage type, geographic origin, or time of isolation that spanned over 2
      decades (1978 to 2004). Attachment and invasion assays, however, indicate that,
      among ET-3 isolates, there is a distinct invasive bacterial subpopulation that is
      more readily recovered from eggs and clinical cases in humans than from chicken
      cecal samples. These observations support the hypothesis that the specialized
      ability of S. Enteritidis to infect the avian reproductive tract and contaminate
      eggs has been critical in its emergence as a frequent cause of human illness.

PMID- 16640301
TI  - Influence of sampling methodology on reported incidence of Salmonella in poultry.
AB  - Salmonella is a major pathogen associated with poultry food products. Over the
      past 20 years, pressure to reduce human illness from poultry-related
      salmonellosis has resulted in intensive research activity as well as stronger
      regulatory standards in Europe, North America, and, because of international
      trade policies, throughout the world. In the United States, implementation of a
      Hazard Analysis Critical Control Point-based inspection program has been credited
      with reducing the incidence of Salmonella-positive carcasses from approximately
      20 to 10%. Since 1998, however, the reported incidence of Salmonella in retail
      poultry from 12 countries implementing similar pathogen reduction programs,
      including the United States, has averaged 29% positive for Salmonella. Although
      these reports examined products at retail outlets and used a variety of sampling
      methodologies, these results appear to contradict the U.S. Department of
      Agriculture claims for Salmonella reduction. The purpose of this review is to
      examine this contradiction with a focus on the potential impact of sampling
      methodology on reported incidences of Salmonella.

PMID- 16640302
TI  - Genetics-based methods for detection of Salmonella spp. in foods.
AB  - Genetic methods are now at the forefront of foodborne pathogen testing. The
      sensitivity, specificity, and inclusivity advantages offered by deoxyribonucleic
      acid (DNA) probe technology have driven an intense effort in methods development
      over the past 20 years. DNA probe-based methods for Salmonella spp. and other
      pathogens have progressed from time-consuming procedures involving the use of
      radioisotopes to simple, high throughput, automated assays. The analytical
      sensitivity of nucleic acid amplification technology has facilitated a reduction
      in analysis time by allowing enriched samples to be tested for previously
      undetectable quantities of analyte. This article will trace the evolution of the
      development of genetic methods for detection of Salmonella in foods, review the
      basic assay formats and their advantages and limitations, and discuss method
      performance characteristics and considerations for selection of methods.

PMID- 16640303
TI  - The use of biosensor and microarray techniques in the rapid detection and
      identification of salmonellae.
AB  - The ever-present need for rapid and sensitive assay methods to detect foodborne
      pathogens, particularly the salmonellae, has led to increased incorporation of
      biosensor technology into microarray and other platforms. The use of mimetics and
      aptamers has been added to these procedures. Nanoparticles, particularly
      incorporating fluorophores and quantum dots into various procedures, have
      decreased the size of instrumentation while increasing automation, sensitivity,
      and rapidity of results. This article will deal mainly with assays involving the
      salmonellae.

PMID- 16640304
TI  - Cutting boards in Salmonella cross-contamination.
AB  - Cutting boards are commonly perceived as important fomites in cross-contamination
      of foods with agents such as Salmonella spp., despite the lack of supporting
      epidemiological data. A variety of woods and plastics have been used to make work
      surfaces for cutting. In general, wood is said to dull knives less than plastic,
      and plastic is seen as less porous than wood. Research to model the hypothetical
      cross-contamination has been done in a variety of ways and has yielded a variety
      of results. At least some of the work with knife-scarred plastic indicates that
      the surface is very difficult to clean and disinfect, although this may vary
      among the polymers used. High-density polyethylene, which is most used in
      commercial applications, has been shown to delaminate in response to knife
      scarring. Wood is intrinsically porous, which allows food juices and bacteria to
      enter the body of the wood unless a highly hydrophobic residue covers the
      surface. The moisture is drawn in by capillary action until there is no more free
      fluid on the surface, at which point immigration ceases. Bacteria in the wood
      pores are not killed instantly, but neither do they return to the surface.
      Destructive sampling reveals infectious bacteria for hours, but resurrection of
      these bacteria via knife edges has not been demonstrated. Small plastic cutting
      boards can be cleaned in a dishwasher (as can some specially treated wooden
      boards), but the dishwasher may distribute the bacteria onto other food-contact
      surfaces. Most small wooden boards (i.e., those with no metal joiners in them)
      can be sterilized in a microwave oven, but this should be unnecessary if
      accumulation of food residues is prevented. However, 2 epidemiological studies
      seem to show that cutting board cleaning habits have little influence on the
      incidence of sporadic salmonellosis. Further, one of these studies indicated that
      use of plastic cutting boards in home kitchens is hazardous, whereas use of
      wooden cutting boards is not.

PMID- 16640305
TI  - Modeling and risk assessment for Salmonella in meat and poultry.
AB  - Microbial risk assessment is rapidly becoming a well-recognized concept in the
      management of food- and waterborne microbial hazards. The process of conducting a
      risk assessment is a structured, systematic approach to integrate and evaluate
      information from diverse sources concerning the origin and fate of pathogens
      along the food chain and to determine the magnitude of public health risks.
      Quantitative modeling of the sources, prevalence, numbers, and behavior of food
      chain pathogens, such as Salmonella, and of the host/pathogen interaction and
      consequences are providing scientific information and insights useful for
      decision makers in managing the safety of the food supply.

PMID- 16640306
TI  - Surveillance for human Salmonella infections in the United States.
AB  - Surveillance for human Salmonella infections plays a critical role in
      understanding and controlling foodborne illness due to Salmonella. Along with its
      public health partners, the Centers for Disease Control and Prevention (CDC) has
      several surveillance systems that collect information on Salmonella infections in
      the United States. The National Salmonella Surveillance System, begun in 1962,
      receives reports of laboratory-confirmed Salmonella infections through state
      public health laboratories. Salmonella outbreaks are reported by state and local
      health departments through the Foodborne Disease Outbreak Reporting System, which
      became a Web-based, electronic system (eFORS) in 2001. PulseNet facilitates the
      detection of clusters of Salmonella infections through standardized molecular
      subtyping (DNA "fingerprinting") of isolates and maintenance of "fingerprint"
      databases. The National Antimicrobial Resistance Monitoring System for Enteric
      Bacteria (NARMS) monitors antimicrobial resistance in Salmonella by
      susceptibility testing of every 20th Salmonella isolate received by state and
      local public health laboratories. FootNet is an active surveillance system that
      monitors Salmonella infections in sentinel areas, providing population-based
      estimates of infection rates. Efforts are underway to electronically link all of
      the Salmonella surveillance systems at CDC to facilitate optimum use of available
      data and minimize duplication.

PMID- 16640307
TI  - Salmonella surveillance in Australia--created from adversity.
AB  - A national scheme of Salmonella surveillance emerged in Australia as a direct
      result of high-profile outbreaks in 1977. A typing laboratory in Victoria put
      together a working model using the computer technology available at the time. The
      evolving information-gathering system has stood the test of time and has provided
      an invaluable bank of information covering isolations from humans and other
      sources. The databases have been used effectively in detecting trends and
      outbreaks and have assisted in the solution of public health problems--even
      extending internationally. The way in which this has been done and the lessons
      learned are described.

PMID- 16640308
TI  - An analytical method to screen for six thyreostatic drug residues in the thyroid
      gland and muscle tissues of food producing animals by liquid chromatography with
      ultraviolet absorption detection and liquid chromatography/mass spectrometry.
AB  - A method was developed and validated to screen for residues of the thyreostatic
      drugs, tapazole (TAP), mercaptobenzimidazole (MBI), thiouracil (TU),
      methylthiouracil (MTU), propylthiouracil (PrTU), and phenylthiouracil (PhTU) in
      bovine, equine, ovine, and porcine thyroid and muscle tissues at concentrations >
      or = 5 ng/g using 2-methoxy-mercaptobenzimidazole (MeMBI) and dimethylthiouracil
      (DMTU) as internal standards. In this method, the drugs were solvent extracted
      from thyroid and muscle tissue and cleaned up on an amino-propyl solid-phase
      extraction (SPE) cartridge. The unretained fraction containing TAP and MBI and
      the internal standard, MeMBI, was collected as Fraction 1. The retained fraction
      containing TU, MTU, PrTU, PhTU, and the internal standard, DMTU, was eluted with
      3% acetic acid-isopropanol as Fraction 2. Fraction 1 was further cleaned up on an
      alumina B SPE cartridge and analyzed by gradient elution on a C18 high
      performance liquid chromatography (HPLC) column with ultraviolet detection at
      wavelengths of 255 and 300 nm. Fraction 2 was taken to dryness, derivatized with
      4-chloro-7-nitrobenzo-2-furazan at pH 8, and analyzed by gradient elution on a
      C18 LC column with mass spectrometry (MS) detection. Any "presumptive positive"
      test results were submitted for further analysis by LC/MS/MS. The validated
      method was applied to the analysis of over 300 thyroid tissue samples.

PMID- 16640309
TI  - Alternative methodology for the analysis of progesterone, testosterone, and epi
      testosterone in bovine liver and veal muscle.
AB  - Research has shown that traditional solvent extraction procedures used for the
      analysis of endogenous steroids often give inconsistent recoveries and results.
      However, a single-laboratory validation of a liquid chromatography/tandem mass
      specrometry method using 2 product ions per transition for progesterone,
      testosterone, and epi-testosterone in bovine liver and veal muscle showed
      accuracy and precision to within 23% at concentrations ranging from 0.5 to 2.0
      microg/kg. Homogenized samples were pretreated with methanol to denature
      endogenous enzymes. Following removal of methanol, samples were treated overnight
      with Helix pomatia beta-glucuronidase to deconjugate glucuronide conjugates.
      Alkali digestion of the samples in KOH solutions was done under shaking at 37
      degrees C for 30 min. The digestate was extracted with methyl tert-butyl ether,
      and the extracts were cleaned by partitioning between acetonitrile-hexane,
      followed by solid-phase extraction cleanup on silica cartridges. In bovine liver,
      average recoveries exceeded 54% for all analytes, and the within-run assay
      coefficients of variations were < 6 and 13% for high (2.0 microg/kg) and low (0.3
      microg/kg) analyte concentrations, respectively. In veal muscle, average
      recoveries exceeded 60%, and the analysis of blind spikes gave accuracy estimates
      of over 85%, with coefficients of variation (CVs) < 15% for all analytes. The CVs
      for the multiple reaction monitoring ion ratios for all compounds were < 22% for
      all validation data. The method meets the requirements for confirmatory methods
      as outlined in 2002/657/EC. An analyst is capable of processing up to 20 samples
      within 5 days.

PMID- 16640310
TI  - Peer validation of a method to confirm chloramphenicol in honey by liquid
      chromatography-tandem mass spectrometry.
AB  - Chloramphenicol (CAP) is extracted from an aqueous dilution of honey using ethyl
      acetate. The extracts are evaporated and redissolved in water. CAP is then
      extracted from the aqueous solutions using reversed-phase solid-phase extraction
      cartridges. CAP is eluted from the reversed-phase cartridges with acetonitrile
      water and re-extracted into ethyl acetate. The ethyl acetate is evaporated, and
      the residue is reconstituted in an aqueous solution. Extracts are chromatographed
      using a reversed-phase column and analyzed by electrospray negative mode tandem
      mass spectrometry. Four product ions of precursors m/z 321 or 323 are monitored.
      The method meets confirmation criteria recommended by the U.S. Food and Drug
      Administration and 4-point identification criteria established by the European
      Union. With slight modifications to accommodate different equipment, the method
      was validated in 2 laboratories.

PMID- 16640311
TI  - Risk assessment for children exposed to decabromodiphenyl (oxide) ether (Deca) in
      the United States.
AB  - Decabromodiphenyl (oxide) ether (Deca) is a widely used brominated flame
      retardant in the United States predominantly in the hard-plastic housings of
      consumer electronics and in flame-retarded backing on textiles used in furniture.
      A child-specific exposure assessment of Deca was performed for the US
      Environmental Protection Agency's Voluntary Children's Chemical Evaluation
      Program (VCCEP). The VCCEP guidance for a tier 1 exposure assessment requires
      that a screening-level assessment be conducted using currently available data and
      conservative assumptions. For Deca, relevant exposure pathways considered were
      general environmental exposures (e.g., exposures to contaminated soil, dust, air,
      and food), breast milk exposures, inhalation of Deca-containing particulates in
      air, and mouthing Deca-containing consumer products. For each of these scenarios,
      a mid-range and upper estimate of age-appropriate intakes were calculated. The
      calculated intakes indicate that, despite the uncertainties, children appear to
      be exposed to Deca at levels at least 1 order of magnitude, with most being
      several orders of magnitude, below the National Academy of Sciences reference
      dose for Deca of 4 mg/kg/d. This analysis indicates that, using the available
      data, current levels of Deca in the United States are unlikely to represent an
      adverse health risk for children.

PMID- 16640312
TI  - Assessment of persistency and bioaccumulation in pesticide registration
      frameworks within the Organization for Economic Cooperation and Development.
AB  - This article describes the results of a survey conducted in 2003 on methods used
      by different member countries within the Organization for Economic Cooperation
      and Development (OECD) to evaluate persistent and bioaccumulative pesticides. The
      objectives were to establish the differences in taking persistence (P) and
      bioaccumulation (B) into account in the decision-making process and to establish
      the influence of the assessors' subjectivity to data interpretation and data
      selection. Fifteen countries participated in the survey, which generated a vast
      amount of information on decision making, risk assessment, risk classification,
      and data treatment. Survey results indicated clear differences in approaches to
      the use of P, B, and toxicity (T) information in scientific risk assessment.
      Using the same data for 2 different pesticides, several OECD member countries
      responded differently in classifying both substances as P, B, and T. Differences
      in regulatory decision-making were also apparent because, based on identical
      classifications, several OECD member countries adopted different decisions on
      pesticide registration; recommendations were based, with respect to technical
      guidance, on data handling, training of assessors, and handling of uncertainty in
      risk assessment.

PMID- 16640313
TI  - Incorporating sediment stability within the management of contaminated sediment
      sites: a synthesis approach.
AB  - At the Third International Conference on Remediation of Contaminated Sediments, a
      panel discussion was held to consider how best to incorporate sediment stability
      assessment (SSA) results when managing risks at contaminated sediment sites. This
      remains a challenge to the scientific and regulatory community, especially at
      sites where large volumes of legacy sediment are present below layers of recent
      sediment of better quality, and where in-place management may be viable. Use of a
      suite of empirical and predictive approaches collectively to assess potential
      risks resulting from bed erosion has emerged as the state-of-the-art approach for
      SSA, yet current practice lacks consistent guidance for conducting such
      assessments and for dealing with and communicating implications of uncertainty.
      The regulatory community lacks a decision-making framework that specifically
      incorporates SSA results, though it is a consideration in US Environmental
      Protection Agency (USEPA 2002) Principles for Sediment Management. Practitioners
      have not consistently communicated SSA results from a risk perspective to the
      stakeholder community. We believe this combination of factors, especially the
      inconsistent framing of results in a risk context, has contributed to discounted
      use of sediment stability information in decision making, fostering application
      of the precautionary principle, where removal is viewed as a presumed
      conservative but more expensive approach over in-place management options. We
      assert that the incorporation of SSA in decision making will be improved through
      the use of a consistent SSA assessment framework built around the conceptual site
      model, incorporating multiple lines of evidence detailing the potential impacts
      of large, low-probability events (e.g., the 100-y storm) on exposure and risk,
      and the associated uncertainties. Further advocacy of this approach was realized
      through panel-audience discussion at the conference. The technical methods
      discussed are not new; rather, it is the synthesis approach emphasized here,
      which by providing a framework for the systematic evaluation of how SSA is best
      addressed from site to site, makes the results of SSA efforts more accessible and
      acceptable to stakeholders and decision makers.

PMID- 16640314
TI  - Uncertainties in sediment erodibility estimates due to a lack of standards for
      experimental protocols and data interpretation.
AB  - Quantitative prediction of the erodibility of muds and mud-sand mixtures is, at
      present, seldom possible without resorting to direct measurements, preferably in
      situ. A variety of devices and protocols have been developed for erosion testing,
      but a considerable degree of uncertainty remains with regard to the accuracy and
      comparability of the resulting data. This paper argues that differences in
      experimental protocols and data analysis procedures are a major contributing
      factor to uncertainty in estimates of sediment erodibility. In particular, the
      likelihood of a time-dependent erosion rate response under typical erosion
      testing conditions means that the time history of applied forcing and the chosen
      protocols for analyzing and interpreting data directly affect derived erosion
      parameters. Several straightforward ways to address this problem are suggested,
      including standardization of experimental design and data analysis protocols,
      explicit recognition and adoption of appropriate erosion model(s), and allowing
      for potential time/depth changes in erodibility. Experimentalists should also
      archive and share erosion-test time series, not just derived parameters, so that
      data sets may be reanalyzed within a different framework if necessary. An example
      is presented from an intercomparison experiment between the Virginia Institute of
      Marine Sciences Sea Carousel and the University of Maryland Center for
      Environmental Science Microcosm System, carried out in the upper Chesapeake Bay
      (Maryland, USA) in May 2002. Derived parameters appear to be incompatible when
      the data are analyzed using different procedures, but real similarities and
      differences are readily apparent when the data are analyzed using the same
      procedures.

PMID- 16640315
TI  - Why confined aquatic disposal cells often make sense.
AB  - Confined aquatic disposal (CAD) cells are increasingly becoming the selected
      option for the management of unacceptably contaminated sediments. CAD cells are
      selected as the preferred alternative because this approach provides an
      acceptable compromise when cost, logistics, regulatory acceptance, environmental
      risk, and perception of various alternatives are considered. This preference for
      CAD cells often occurs even when other alternatives with similar risk reduction
      and less cost, such as an open water capping alternative, are considered as
      options. This paradox is largely a result of subjective factors that affect
      regulatory acceptance such as public perceptions.

PMID- 16640316
TI  - Uncertainty in experimental techniques for measuring sediment erodability.
AB  - There are many experimental methods currently utilized to measure sediment
      erodability and stability. When utilizing any of the available methods or devices
      to characterize erodability, one must understand the inherent uncertainty
      associated with each technique in relation to the application or expected
      measurement need. In addition, while some uncertainties are unique to a
      particular measurement device or technique, other uncertainties arise from
      variation in sediment conditions or properties. Several widely used devices and
      techniques are discussed with respect to their uncertainties and applicability
      for certain measurements. Finally, suggestions will be made on how to reduce
      uncertainty and manage it in model development.

PMID- 16640317
TI  - Using mathematical models to assess sediment stability.
AB  - The application of mathematical models to a sediment stability study is
      presented, with an emphasis on using models as a component of an effort to
      develop, refine, and potentially validate a conceptual site model (CSM) for
      sediment transport at a study site. The utility of mathematical models is
      discussed, in which the modeling framework consists of linked hydrodynamic,
      sediment transport, and contaminant fate and transport models. Benefits and
      drawbacks of empirically based mechanistic models are presented. An approach for
      integrating modeling analyses into the development, refinement and validation of
      a CSM is provided. This approach focuses on a phased study that combines modeling
      and data-based analyses to test hypotheses related to the CSM and sediment
      stability. Uncertainty in modeling results is a primary concern in sediment
      stability studies, and issues related to model uncertainty are discussed.
      Finally, communication of modeling results to stakeholders is addressed.

PMID- 16640318
TI  - Risk-based decision making to manage contaminated sediments.
AB  - This paper summarizes discussion among the 7 authors who served on an expert
      panel at the Third Battelle International Conference on Remediation of
      Contaminated Sediments held in New Orleans, Louisiana, USA, in January 2005. In
      this article, the authors review how sediment management decisions are currently
      made and address the question of how management decisions should be made in the
      future. It is arguably the case that sediment remediation presents greater
      challenges and more complexity than traditional land-based clean-ups. Although
      understanding of these challenges and complexities has grown over the last 25 y,
      there has been, until recently, relatively little innovation in the approaches
      used to manage the environmental risks posed by contaminated sediments. New
      methods that facilitate a more rigorous analysis of the multiple criteria
      considered in decision making have been developed. These methods, collectively
      known as multicriteria decision analysis (MCDA), coupled with the use of
      comparative-risk assessment and cost/benefit analysis, are proposed as an
      effective, efficient, and credible foundation for evaluating remedy alternatives
      at contaminated sediment sites.

PMID- 16640319
TI  - Importance of implementation and residual risk analyses in sediment remediation.
AB  - Management strategies for addressing contaminated sediments can include a wide
      range of actions, ranging from no action, to the use of engineering controls, to
      the use of more aggressive, intrusive activities related to removing, containing,
      or treating sediments because of environmental or navigation considerations. Risk
      assessment provides a useful foundation for understanding the environmental
      benefits, residual hazards, and engineering limitations of different remedy
      alternatives and for identifying or ranking management options. This article,
      part of a series of panel discussion papers on sediment remediation presented at
      the Third International Conference on Remediation of Contaminated Sediments held
      20-25 January 2005 in New Orleans, Louisiana, USA, reviews 2 types of risk that
      deserve careful consideration when evaluating remedy alternatives. The evaluation
      of remedy implementation risks addresses predominantly short-term engineering
      issues, such as worker and community health and safety, equipment failures, and
      accident rates. The evaluation of residual risks addresses predominantly longer
      term biological and environmental issues, such as ecological recovery,
      bioaccumulation, and relative changes in exposure and effects to humans, aquatic
      biota, and wildlife. Understanding the important pathways for contaminant
      exposure, the human and wildlife populations potentially at risk, and the
      possible hazards associated with the implementation of different engineering
      options will contribute to informed decision making with regard to short- and
      long-term effectiveness, implementability, and potential environmental hazards.

PMID- 16640320
TI  - The role of monitored natural recovery in sediment remediation.
AB  - The long-term goal of monitored natural recovery (MNR) is to achieve ecological
      recovery of biological endpoints in order to protect human and ecological health.
      Insofar as ecological recovery is affected by surface-sediment-contaminant
      concentrations, the primary recovery processes for MNR are natural sediment
      burial and contaminant transformation and weathering to less toxic forms. This
      paper discusses the overall approach for effective implementation of MNR for
      contaminated sediment sites. Several lines of evidence that may be used to
      demonstrate natural recovery processes are summarized, including documentation of
      source control; evidence of contaminant burial; measurement of surface sediment
      mixing depths and the active sediment benthic layer; measurement of sediment
      stability; contaminant transformation and weathering; modeling sediment
      transport, contaminant transport, and ecological recovery; measuring ecological
      recovery and long-term risk reduction; knowledge of future plans for use and
      development of the site; and watershed and institutional controls. In general,
      some form of natural recovery is expected and should be included as part of a
      remedy at virtually all contaminated sediment sites. Further, MNR investigations
      and an understanding of natural recovery processes provide cost-effective
      information and support the evaluation of more aggressive remedies such as
      capping, dredging, and the use of novel amendments. The risk of dredging or
      capping may be greater than the risk of leaving sediments in place at sites where
      capping or dredging offer little long-term environmental gain but pose
      significant short-term risks for workers, local communities, and the environment.

PMID- 16640321
TI  - Panel discussion: remedy effectiveness: what works, what doesn't?
AB  - As contaminated sediment sites in freshwater and marine environments come under
      increasing scrutiny, and the importance of these sites with regard to ecological
      and human health is better understood, the number of contaminated sediment sites
      requiring risk characterization and management is increasing. Risk reduction must
      be the long-term goal of all sediment management practices. Risk management
      strategies in aquatic environments focus on mitigating potential exposure
      pathways for contaminants that may pose an ecological or human health risk over
      time. Sediment management practices include dredging ("environmental dredging"),
      capping, monitored natural recovery, and combinations of these generic response
      actions. A Remedy Effectiveness Panel was selected to identify and discuss the
      key issues associated with the performance of these generic response actions for
      contaminated sediments. The panel convened in New Orleans on 26 January 2005 at
      Battelle's Third International Conference on the Remediation of Contaminated
      Sediments and made 3 presentations on response actions to conference attendees
      followed by an open dialog between attendees and panel members. This article
      introduces the 3 generic response actions, identifies key topics from the open
      dialog and presents opinions expressed, and provides a summary and observations.

PMID- 16640322
TI  - European environmental management: moving to an ecosystem approach.
AB  - The European Union has adopted several environmental directives, strategies,
      recommendations, and agreements that require a shift from local- or regional
      based regulations to more ecosystem-based, holistic environmental management.
      Over the next decade, environmental management in Europe is likely to focus more
      on biological and ecological conditions rather than physical and chemical
      conditions, with ecosystem health at the center of regulation and management
      decision making. Successful implementation of this new ecosystem management and
      strategic assessment process in Europe will require the integration of regulatory
      and technical information and extensive collaboration from among European Union
      member countries, between agencies, and across disciplines to an unprecedented
      degree. It will also require extensive efforts to adapt current systems of
      environmental assessment and management to the basin and ecosystem level, across
      media and habitats, and considering a much broader set of impacts on ecosystem
      status than is currently addressed in most risk assessments. This will require
      the understanding, integration, and communication of economic, ecological,
      hydrological, and other processes across many spatial and temporal scales. This
      article discusses these challenges and describes some of the research initiatives
      that will help achieve integrated ecosystem management in Europe.

PMID- 16640323
TI  - Population-scale assessment endpoints in ecological risk assessment. Part 1:
      Reflections of stakeholder values.
AB  - The selection of appropriate assessment endpoints is a basic element of an
      ecological risk assessment, especially at regional or watershed scales. Because
      ecological services often are tied to specific species, the risk to populations
      is a critical endpoint and feature of ecological risk assessments. The first item
      is a discussion of the replacement of population-level risk assessment with the
      construct of a population-scale assessment endpoint. Next, the criteria that are
      currently used for assessment endpoints are reviewed and evaluated for utility in
      an ecological risk assessment. Following this examination, assessment endpoints
      from a number of regional-scale ecological risk assessments are compared. The
      outcome of this evaluation is that population-scale assessment endpoints are
      important expressions of the valued components of ecological structures. Finally,
      a few recommendations for the selection of assessment endpoints at a population
      scale are listed.

PMID- 16640324
TI  - From optimization to adaptation: shifting paradigms in environmental management
      and their application to remedial decisions.
AB  - Current uncertainties in our understanding of ecosystems require shifting from
      optimization-based management to an adaptive management paradigm. Risk managers
      routinely make suboptimal decisions because they are forced to predict
      environmental response to different management policies in the face of complex
      environmental challenges, changing environmental conditions, and even changing
      social priorities. Rather than force risk managers to make single suboptimal
      management choices, adaptive management explicitly acknowledges the uncertainties
      at the time of the decision, providing mechanisms to design and institute a set
      of more flexible alternatives that can be monitored to gain information and
      reduce the uncertainties associated with future management decisions. Although
      adaptive management concepts were introduced more than 20 y ago, their
      implementation has often been limited or piecemeal, especially in remedial
      decision making. We believe that viable tools exist for using adaptive management
      more fully. In this commentary, we propose that an adaptive management approach
      combined with multicriteria decision analysis techniques would result in a more
      efficient management decision-making process as well as more effective
      environmental management strategies. A preliminary framework combining the 2
      concepts is proposed for future testing and discussion.

PMID- 16640325
TI  - Design, synthesis, and progress toward optimization of potent small molecule
      antagonists of CC chemokine receptor 8 (CCR8).
AB  - Activation of CCR8 by its ligand CCL1 may play an important role in diseases such
      as asthma, multiple sclerosis, and cancer. The study of small molecule CCR8
      antagonists will help establish the validation of these hypotheses. We report the
      design, synthesis, and progress toward optimization of potent small molecule CCR8
      antagonists identified from a high-throughput screen. These analogues exhibit
      good potency in binding and chemotaxis assays, show good selectivity versus the
      hERG channel, and have good eADME (early absorption, distribution, metabolism,
      and excretion) profiles.

PMID- 16640326
TI  - Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine
      derivatives. Nicotinic ligands of enhanced subtype selectivity.
AB  - We report the synthesis and pharmacological properties of several cytisine
      derivatives. Among them, two 10-substituted derivatives showed much higher
      selectivities for the alpha4beta2 nAChR subtype in binding assays than cytisine.
      The 9-vinyl derivative was found to have a very similar agonist activity profile
      to that of cytisine.

PMID- 16640327
TI  - Identification of type 1 inosine monophosphate dehydrogenase as an antiangiogenic
      drug target.
AB  - To rapidly discover clinically useful angiogenesis inhibitors, we created and
      screened a library of existing drugs for inhibition of endothelial cell
      proliferation. Mycophenolic acid (MPA), an immunosuppressive drug, was found to
      potently inhibit endothelial cell proliferation in vitro and block tumor-induced
      angiogenesis in vivo. Using RNA interference, we found that knockdown of one of
      the two known isoforms of inosine monophosphate dehydrogenase (IMPDH-1) is
      sufficient to cause endothelial cell cycle arrest.

PMID- 16640328
TI  - Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein
      kinase C epsilon and eta.
AB  - Conventional (alpha, betaI, betaII, gamma) and novel (delta, epsilon, eta, theta)
      protein kinase C (PKC) isozymes are main targets of tumor promoters, such as
      phorbol esters and indolactam-V (ILV). We have recently found that 1-hexyl
      derivatives of indolinelactam-V (2, 3), in which the indole ring of ILV was
      replaced with the indoline ring, showed a binding preference for novel PKCs over
      conventional PKCs. To develop a new ILV analogue displaying increased synthetic
      accessibility and improved binding selectivity for novel PKCs, we have designed 8
      octyl-benzolactam-V9 (4), a simple analogue without the pyrrolidine moiety of 2
      and 3. Compound 4 showed significant binding selectivity for isolated C1B domains
      of novel PKCs. Moreover, 4 translocated PKC epsilon and eta from the cytoplasm to
      the plasma membrane of HeLa cells at 1 microM, whereas other PKC isozymes did not
      respond even at 10 microM. These results indicate that 4 could be a selective
      activator for PKC epsilon and eta.

PMID- 16640329
TI  - Orthogonal activation of the reengineered A3 adenosine receptor (neoceptor) using
      tailored nucleoside agonists.
AB  - An alternative approach to overcome the inherent lack of specificity of
      conventional agonist therapy can be the reengineering of the GPCRs and their
      agonists. A reengineered receptor (neoceptor) could be selectively activated by a
      modified agonist, but not by the endogenous agonist. Assisted by rhodopsin-based
      molecular modeling, we pinpointed mutations of the A(3) adenosine receptor (AR)
      for selective affinity enhancement following complementary modifications of
      adenosine. Ribose modifications examined included, at 3': amino, aminomethyl,
      azido, guanidino, ureido; and at 5': uronamido, azidodeoxy. N(6)-Variations
      included 3-iodobenzyl, 5-chloro-2-methyloxybenzyl, and methyl. An N(6)-3
      iodobenzyl-3'-ureido adenosine derivative 10 activated phospholipase C in COS-7
      cells (EC(50) = 0.18 microM) or phospholipase D in chick primary cardiomyocytes,
      both mediated by a mutant (H272E), but not the wild-type, A(3)AR. The affinity
      enhancements for 10 and the corresponding 3'-acetamidomethyl analogue 6 were >100
      fold and >20-fold, respectively. 10 concentration-dependently protected
      cardiomyocytes transfected with the neoceptor against hypoxia. Unlike 10,
      adenosine activated the wild-type A(3)AR (EC(50) of 1.0 microM), but had no
      effect on the H272E mutant A(3)AR (100 microM). Compound 10 was inactive at human
      A(1), A(2A), and A(2B)ARs. The orthogonal pair comprising an engineered receptor
      and a modified agonist should be useful for elucidating signaling pathways and
      could be therapeutically applied to diseases following organ-targeted delivery of
      the neoceptor gene.

PMID- 16640330
TI  - Structure-based drug design of a novel family of PPARgamma partial agonists:
      virtual screening, X-ray crystallography, and in vitro/in vivo biological
      activities.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is well-known as the
      receptor of thiazolidinedione antidiabetic drugs. In this paper, we present a
      successful example of employing structure-based virtual screening, a method that
      combines shape-based database search with a docking study and analogue search, to
      discover a novel family of PPARgamma agonists based upon pyrazol-5
      ylbenzenesulfonamide. Two analogues in the family show high affinity for, and
      specificity to, PPARgamma and act as partial agonists. They also demonstrate
      glucose-lowering efficacy in vivo. A structural biology study reveals that they
      both adopt a distinct binding mode and have no H-bonding interactions with
      PPARgamma. The absence of H-bonding interaction with the protein provides an
      explanation why both function as partial agonists since most full agonists form
      conserved H-bonds with the activation function helix (AF-2 helix) which, in turn,
      enhances the recruitment of coactivators. Moreover, the structural biology and
      computer docking studies reveal the specificity of the compounds for PPARgamma
      could be due to the restricted access to the binding pocket of other PPAR
      subtypes, i.e., PPARalpha and PPARdelta, and steric hindrance upon the ligand
      binding.

PMID- 16640331
TI  - Development of quantitative structure-binding affinity relationship models based
      on novel geometrical chemical descriptors of the protein-ligand interfaces.
AB  - Novel geometrical chemical descriptors have been derived on the basis of the
      computational geometry of protein-ligand interfaces and Pauling atomic
      electronegativities (EN). Delaunay tessellation has been applied to a diverse set
      of 517 X-ray characterized protein-ligand complexes yielding a unique collection
      of interfacial nearest neighbor atomic quadruplets for each complex. Each
      quadruplet composition was characterized by a single descriptor calculated as the
      sum of the EN values for the four participating atom types. We termed these
      simple descriptors generated from atomic EN values and derived with the Delaunay
      Tessellation the ENTess descriptors and used them in the variable selection k
      nearest neighbor quantitative structure-binding affinity relationship (QSBR)
      studies of 264 diverse protein-ligand complexes with known binding constants.
      Twenty-four complexes with chemically dissimilar ligands were set aside as an
      independent validation set, and the remaining dataset of 240 complexes was
      divided into multiple training and test sets. The best models were characterized
      by the leave-one-out cross-validated correlation coefficient q(2) as high as 0.66
      for the training set and the correlation coefficient R(2) as high as 0.83 for the
      test set. The high predictive power of these models was confirmed independently
      by applying them to the validation set of 24 complexes yielding R(2) as high as
      0.85. We conclude that QSBR models built with the ENTess descriptors can be
      instrumental for predicting the binding affinity of receptor-ligand complexes.

PMID- 16640332
TI  - Novel benzofuran derivatives for PET imaging of beta-amyloid plaques in
      Alzheimer's disease brains.
AB  - A novel series of benzofuran derivatives as potential positron emission
      tomography (PET) tracers targeting amyloid plaques in Alzheimer's disease (AD)
      were synthesized and evaluated. The syntheses of benzofurans were successfully
      achieved by an intramolecular Wittig reaction between triphenylphosphonium salt
      and 4-nitrobenzoyl chloride. When in vitro binding studies using AD brain gray
      matter homogenates were carried out with a series of benzofuran derivatives, all
      the derivatives examined displayed high binding affinities with K(i) values in
      the subnanomolar range. Among these benzofuran derivatives, compound 8, 5-hydroxy
      2-(4-methyaminophenyl)benzofuran, showed the lowest K(i) value (0.7 nM). In vitro
      fluorescent labeling of AD sections with compound 8 intensely stained not only
      amyloid plaques, but also neurofibrillary tangles. The (11)C labeled compound 8,
      [(11)C]8, was prepared by reacting the normethyl precursor, 5-hydroxy-2-(4
      aminophenyl)benzofuran, with [(11)C]methyl triflate. The [(11)C]8 displayed
      moderate lipophilicity (log P = 2.36), very good brain penetration (4.8%ID/g at 2
      min after iv injection in mice), and rapid washout from normal brains (0.4 and
      0.2%ID/g at 30 and 60 min, respectively). In addition, this PET tracer showed in
      vivo amyloid plaque labeling in APP transgenic mice. Taken together, the data
      suggest that a relatively simple benzofuran derivative, [(11)C]8, may be a useful
      candidate PET tracer for detecting amyloid plaques in the brains of patients with
      Alzheimer's disease.

PMID- 16640333
TI  - Second generation, orally active, antimalarial, artemisinin-derived trioxane
      dimers with high stability, efficacy, and anticancer activity.
AB  - In only two steps and in 63% overall yield, naturally occurring 1,2,4-trioxane
      artemisinin (1) was converted into C-10-carba trioxane conjugated diene dimer 4.
      This new dimer was then transformed easily in one additional 4 + 2-cycloaddition
      step into phthalate dimer 5, and further modification led to bis-benzyl alcohol
      dimer 7 and its phosphorylated analogues 8 and 9. Bis-benzyl alcohol dimer 7 is
      the most antimalarially active in vitro, 10 times more potent than artemisinin
      (1). Bis-benzyl alcohol dimer 7 is approximately 1.5 times more orally
      efficacious in rodents than the antimalarial drug sodium artesunate and is about
      37 times more efficacious than sodium artesunate via subcutaneous administration.
      Both dimers 5 and 7 are thermally stable neat even at 60 degrees C for 24 h.
      Phthalate dimer 5 is very highly growth inhibitory but not cytotoxic toward
      several human cancer cell lines; both dimers 5 and 7 very efficiently and
      selectively kill human cervical cancer cells in vitro in a dose-dependent manner
      with no cytotoxic effects on normal cervical cells.

PMID- 16640334
TI  - [2-11C]isopropyl-, [1-11C]ethyl-, and [11C]methyl-labeled phenoxyphenyl acetamide
      derivatives as positron emission tomography ligands for the peripheral
      benzodiazepine receptor: radiosynthesis, uptake, and in vivo binding in brain.
AB  - The peripheral benzodiazepine receptor (PBR) is widely expressed in peripheral
      tissues, blood cells, and in glia cells in the brain. We have previously
      developed two positron emission tomography (PET) ligands, N-(2-[(11)C],5
      dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([(11)C]2) and its
      [(18)F]fluoroethyl analogue ([(18)F]6), for the current investigation of PBR in
      the human brain. The aim of this study was to label the potent PBR agonist N-(4
      chloro-2-phenoxyphenyl)-N-(isopropoxybenzyl)acetamide (3) and its ethyl (7) and
      methyl (8) homologues with (11)C and to evaluate them as PET ligands for PBR with
      mice, rats, and monkeys. Ligands [(11)C]3, [(11)C]7, and [(11)C]8 were
      synthesized by alkylation of phenol precursor 9 with 2-[2-(11)C]iodopropane
      ([(11)C]10), [1-(11)C]iodoethane ([(11)C]11), and [(11)C]iodomethane ([(11)C]12),
      respectively. The alkylating agent [(11)C]10 or [(11)C]11 was prepared by
      reacting CH(3)MgBr with [(11)C]CO(2), followed by reduction with LiAlH(4) and
      iodination with HI. In vitro quantitative autoradiography determined that 3, 7,
      and 8 had potent binding affinities (K(i) = 0.07-0.19 nM) for PBR in the rat
      brain. These [(11)C]ligands could pass across the blood-brain barrier and enter
      the rat brain (0.17-0.32% of injected dose per gram wet tissue). Ex vivo
      autoradiography showed that the [(11)C]ligands preferably distributed in the
      olfactory bulb and cerebellum, two regions with richer PBR density in the rat
      brain. The co-injection of PBR-selective 2 reduced the [(11)C]ligand binding in
      the two regions, suggesting that binding in the rat brain was specific to PBR.
      PET study determined that the [(11)C]ligands preferably accumulate in the
      occipital cortex of the monkey brain, a region with a high density of PBR in the
      primate brain. Moreover, in vivo binding of the methyl homologue [(11)C]8 in the
      monkey brain could be inhibited by PBR-selective 2 or 1, indicating that some of
      the [(11)C]8 binding was due to PBR. Metabolite analysis demonstrated that these
      [(11)C]ligands were metabolized by debenzylation to polar products mainly in the
      plasma.

PMID- 16640335
TI  - Indanesulfonamides as carbonic anhydrase inhibitors. Toward structure-based
      design of selective inhibitors of the tumor-associated isozyme CA IX.
AB  - Carbonic anhydrases are ubiquitous metalloenzymes which are involved in
      fundamental processes (i.e., acid-base regulation, respiration, calcification,
      etc.). The carbonic anhydrase isozyme IX becomes an interesting pharmacological
      target due to its overexpression in cancer and its absence in normal tissue.
      Therefore, several indanesulfonamides were synthesized and tested for their
      inhibition both against the human CA IX and against two other biologically
      relevant isozymes (CA I and II). Structure-activity relationships are discussed
      and point out different compounds for its selectivity and activity against CA IX.
      To establish preliminary hypothesis for the design of new isozyme-selective CA IX
      inhibitors, we conducted molecular modeling. We describe here the first human CA
      IX model built by homology with another CA isozyme already crystallized. Docking
      studies were performed to explore the binding mode of our indanesulfonamide
      derivatives.

PMID- 16640336
TI  - Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine
      protease and HCV subgenomic RNA replication.
AB  - Introduction of various modified prolines at P(2) and optimization of the P(1)
      side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide
      inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency
      (K(i)*= 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA
      replication with IC(50) and IC(90) of 40 and 100 nM, respectively. Recently,
      antiviral activity of 24 was demonstrated with inhibition of the full-length
      genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness
      of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA
      replicons.

PMID- 16640337
TI  - Biarylaniline phenethanolamines as potent and selective beta3 adrenergic receptor
      agonists.
AB  - The synthesis of a series of phenethanolamine aniline agonists that contain an
      aniline ring on the right-hand side of the molecule substituted at the meta
      position with a benzoic acid or a pyridyl carboxylate is described. Several of
      the analogues (e.g., 34, 36-38, 40, and 44) have high beta(3) adrenergic receptor
      (AR) potency and selectivity against beta(1) and beta(2) ARs in Chinese hamster
      ovary (CHO) cells expressing beta ARs. The dog pharmacokinetic profile of some of
      these analogues showed >25% oral bioavailability and po half-lives of at least
      1.5 h. Among the compounds described herein, the 3,3'-biarylaniline carboxylate
      derivatives 36, 38 and the phenylpyridyl derivative 44 demonstrated outstanding
      in vitro properties and reasonable dog pharmacokinetic profiles. These three
      analogues also showed dose dependent beta(3) AR mediated responses in mice. The
      ease of synthesis and superior dog pharmacokinetics of compound 38 relative to
      that of 44 in combination with its in vitro profile led us to choose this
      compound as a development candidate for the treatment of type 2 diabetes.

PMID- 16640338
TI  - (S)-4,5-dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid
      polyethers: a solution to nephrotoxicity.
AB  - Previous studies revealed that within a family of ligands the more lipophilic
      chelators have better iron-clearing efficiency. The larger the log P(app) value
      of the compound, the better the iron-clearing efficiency. What is also clear from
      the data is that although the relative effects of log P(app) changes are
      essentially the same through different families, there are differences in
      absolute value between families. However, there also exists a second, albeit
      somewhat more disturbing, relationship. In all sets of ligands, the most
      lipophilic chelator is always the most toxic. The current study focuses on
      designing ligands that balance the lipophilicity/toxicity problem while iron
      clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2
      hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH(3)O)
      DADFT, 6] indicated that this methyl ether was a ligand with excellent iron
      clearing efficiency in both rodents and primates; however, it was too toxic. On
      the basis of this finding, a less lipophilic, more water-soluble ligand than 6
      was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4
      methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE, 11], a polyether
      analogue, along with its ethyl and isopropyl esters. The parent polyether and its
      isopropyl and ethyl esters were all shown to be highly efficient iron chelators
      in both rodents and primates. A comparison of 11 in rodents with the
      desferrithiocin analogue (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4
      thiazolecarboxylic acid [(S)-4'-(HO)-DADFT, 1] revealed the polyether to be more
      tolerable, achieving higher concentrations in the liver and significantly lower
      concentrations in the kidney. The lower renal drug levels are in keeping with the
      profound difference in the architectural changes seen in the kidney of rodents
      given 1 versus those treated with 11.

PMID- 16640339
TI  - Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly
      potent Anti-HIV-1 activity.
AB  - We incorporated various polar groups into previously described piperidine-4
      carboxamide CCR5 antagonists to improve their metabolic stability in human
      hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4
      benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed
      both high metabolic stability and good inhibitory activity of HIV-1 envelope
      mediated membrane fusion (IC(50) = 5.8 nM). Further optimization to increase
      potency led to the discovery of 1-acetyl-N-{3-[4-(4-carbamoylbenzyl)piperidin-1
      yl]propyl}-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide (5m, TAK-220),
      which showed high CCR5 binding affinity (IC(50) = 3.5 nM) and potent inhibition
      of membrane fusion (IC(50) = 0.42 nM), as well as good metabolic stability.
      Compound 5m strongly inhibited the replication of CCR5-using HIV-1 clinical
      isolates in human peripheral blood mononuclear cells (mean EC(50) = 1.1 nM,
      EC(90) = 13 nM) and exhibited a good pharmacokinetic profile in monkeys (BA =
      29%). This compound has been chosen as a clinical candidate for further
      development.

PMID- 16640340
TI  - Orally active 1,2,4-trioxanes: synthesis and antimalarial assessment of a new
      series of 9-functionalized 3-(1-arylvinyl)-1,2,5-trioxaspiro[5.5]undecanes
      against multi-drug-resistant plasmodium yoelii nigeriensis in mice.
AB  - Using easily accessible keto-trioxanes 7a-g as the starting materials, a series
      of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and
      evaluated for antimalarial activity against multi-drug-resistant Plasmodium
      yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4
      days by oral route. Trioxanes 10, 12, 14, 16, 18, 20, and 22 have shown promising
      antimalarial activity. Trioxanes 14 and 18, the two most active compounds of the
      series, provide 100% and 60% protection at 48 mg/kg x 4 days and 24 mg/kg x 4
      days, respectively. In this model beta-arteether provides 100% and 20% protection
      at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.

PMID- 16640341
TI  - Design, synthesis, and biological evaluation of 4-alkyliden-beta lactams: new
      products with promising antibiotic activity against resistant bacteria.
AB  - The design, synthesis, and antibacterial activity of 4-alkyliden-azetidin-2-ones
      as new antimicrobial agents against multidrug-resistant pathogens is reported. 4
      Alkyliden-azetidin-2-ones were easily obtained using an original protocol
      starting from 4-acetoxy-azetidinones and diazoesters. Parent compounds were
      further elaborated to obtain a small library of 4-alkylidene derivatives. A
      molecular modeling approach using GRID descriptors based on the concept of VRS
      identified attractive drug candidates and contributed to the rationalization of
      functional group effects in QSARs. The in vitro antibacterial activity of the new
      agents was evaluated against 43 recent clinical isolates of antibiotic
      susceptible and -resistant Gram-positive and Gram-negative pathogens by
      determining their minimum inhibitory concentrations (MICs). The most active
      compound showed MIC values ranging from 0.25 to 32 mg/L against some of the
      bacterial species tested. Interestingly, some compounds demonstrated similar
      activity against methicillin-susceptible and -resistant strains of Staphylococcus
      aureus suggesting possible alternative mechanisms of action of these agents,
      supported by citotoxicity and preliminary scanning electron microscopy studies.

PMID- 16640342
TI  - Fluorinated amphiphilic amino acid derivatives as antioxidant carriers: a new
      class of protective agents.
AB  - The use of classical antioxidants is limited by their low bioavailabilities, and
      therefore, high doses are usually required to display significant protective
      activity. In a recent article (J. Med. Chem. 2003, 46, 5230) we showed that the
      ability of the alpha-phenyl-N-tert-butylnitrone (PBN) to restore the viability of
      ATPase-deficient human skin fibroblasts was greatly enhanced by grafting it on a
      fluorinated amphiphilic carrier. With the aim of extending this concept to other
      antioxidants, we present here the design, the synthesis, and the physicochemical
      measurements of a new series of fluorinated amphiphilic antioxidant derivatives.
      The hydroxyl radical scavenging activity and the radical reducing potency of
      these newly designed compounds were respectively demonstrated in an ABTS
      competition and an ABTS(*+) reduction assay. We also showed that the protective
      effects of amphiphilic antioxidants derived from PBN, Trolox (6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid) or lipoic acid (5-[1,2]-dithiolan-3
      ylpentanoic acid) in primary cortical mixed cell cultures exposed to oxidotoxins
      are greatly improved compared to their parent compounds in the following rank
      order: (1) PBN, (2) Trolox, and (3) lipoic acid. In contrast, the protective
      activity of indole-3-propionic acid was slightly decreased by grafting it on the
      amphiphilic carrier. Similar observations were made in in vivo experiments using
      aquatic invertebrate microorganisms, called rotifers, which were exposed to
      lethal concentrations of nonselective (H(2)O(2)) and mitochondria-selective
      (doxorubicin) oxidotoxins. The conclusion of these studies is that fluorinated
      amphiphilic PBN, Trolox, and lipoic acid derivatives exhibit very potent
      protective activities in in vitro and in vivo experiments. The findings
      demonstrated herein therefore strongly suggest that the amphiphilic character
      enhances the bioavailability of the antioxidants and allows for a selective
      targeting of mitochondria.

PMID- 16640344
TI  - Synthesis and structure-activity relationship study of antidiabetic penta-O
      galloyl-D-glucopyranose and its analogues.
AB  - The rapid increase of obesity-associated diabetes has created urgent demands for
      more effective antidiabetic therapies and pharmaceuticals that are able to
      address the problems of hyperglycemia and weight gain simultaneously. Our
      previous studies indicated that the alpha- and beta-anomers of penta-O-galloyl-D
      glucopyranose (PGG), 2 and 3, act as insulin mimetics that bind to and activate
      the insulin receptor, stimulate glucose transport in adipocytes, and reduce blood
      glucose and insulin levels in diabetic and obese animals. In addition, they
      inhibit differentiation of preadipocytes into adipocytes. These activities
      suggest that 2 and 3 may reduce blood glucose without increasing adiposity. To
      investigate the structure-activity relationship of 2 and 3, four series of novel
      compounds were prepared and their glucose transport stimulatory activities were
      measured using a radioactive glucose uptake bioassay. The assay results indicate
      that both the glucose and the galloyl groups are critical to the activity of 2
      and 3. It appears that the glucose core provides an optimal scaffold to present
      the galloyl groups with the correct spatial orientation to induce activity.
      Moreover, the galloyl groups linked to the 1, 2, 3, and 4 positions of glucose
      are essential, while the galloyl group connected to the 6 position of 2 is
      unnecessary for the induction of activity. The discovery that two related novel
      compounds, 6-deoxytetra-O-galloyl-alpha-D-glucopyranose (43) and tetra-O-galloyl
      alpha-D-xylopyranose (59), also possess glucose transport stimulatory activity
      suggests that 2 may be further modified around position 6 to modulate and enhance
      its efficacy. To test this hypothesis, we developed a new synthetic method that
      allows for the stereoselective preparation of derivatives of 2 that are modified
      on C-6. We found that 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-alpha-D
      glucopyranose (80) exhibits a significantly higher glucose transport stimulatory
      activity than 2. Its activity is comparable to that of insulin.

PMID- 16640343
TI  - Differential inhibition of group IVA and group VIA phospholipases A2 by 2
      oxoamides.
AB  - Inhibitors of the Group IVA phospholipase A(2) (GIVA cPLA(2)) and GVIA iPLA(2)
      are useful tools for defining the roles of these enzymes in cellular signaling
      and inflammation. We have developed inhibitors of GVIA iPLA(2) building upon the
      2-oxoamide backbone that are uncharged, containing ester groups. Although the
      most potent inhibitors of GVIA iPLA(2) also inhibited GIVA cPLA(2), there were
      three 2-oxoamide compounds that selectively and weakly inhibited GVIA iPLA(2). We
      further show that several potent 2-oxoamide inhibitors of GIVA cPLA(2) containing
      free carboxylic groups (Kokotos et al. J. Med. Chem. 2002, 45, 2891-2893) do not
      inhibit GVIA iPLA(2) and are, therefore, selective GIVA cPLA(2) inhibitors.

PMID- 16640345
TI  - Biological evaluation of bishydroxymethyl-substituted cage dimeric 1,4
      dihydropyridines as a novel class of p-glycoprotein modulating agents in cancer
      cells.
AB  - A series of N-substituted cage dimeric 1,4-dihydropyridines 3a-e was evaluated as
      inhibitors of membrane efflux pump P-glycoprotein (P-gp) in multidrug resistant
      (mdr) cancer cells. Structure-activity relationships (SAR) and cytotoxic
      properties are discussed. Effective concentrations for overcoming mdr have been
      demonstrated in competition studies with the P-gp substrate epirubicin.

PMID- 16640346
TI  - Synthesis of biphenyltrienes as probes for beta-amyloid plaques.
AB  - We report a series of p-hydroxy-, p-amino-, p-monomethylamino-, and p
      monofluoroethylamino-substituted biphenyltrienes that displayed high binding
      affinities to beta-amyloid plaques. In an in vitro binding assay using postmortem
      brain homogenates of Alzheimer's patients and [(125)I]9, the triene compounds
      showed excellent binding affinities. When labeled with suitable radionuclides,
      they are useful as in vivo imaging agents for detecting Abeta plaques in the
      brains of Alzheimer's patients.

PMID- 16640347
TI  - Design and synthesis of hydroxyferroquine derivatives with antimalarial and
      antiviral activities.
AB  - Three ferroquine (FQ) derivatives, closely mimicking the antimalarial drug
      hydroxychloroquine (HCQ), have been prepared. Whereas these organometallic
      compounds provide the expected reduced cytotoxic effects compared to FQ, they
      inhibit in vitro growth of Plasmodium falciparum far better than chloroquine
      (CQ). Moreover, this new class of bioorganometallic compounds exert antiviral
      effects with some selectivity toward SARS-CoV infection. These new drugs may
      offer an interesting alternative for Asia where SARS originated and malaria has
      remained endemic.

PMID- 16640349
TI  - Effect of electrolytes on the excited-state proton transfer and geminate
      recombination.
AB  - Time-resolved emission and steady-state fluorescence techniques are used to study
      the excited-state intermolecular proton transfer from 8-hydroxypyrene-1,3,6
      trisulfonate (HPTS or pyranine) to water in the presence of inert salts, NaCl and
      MgCl(2). At low salt concentrations, up to about 0.5 M MgCl(2) or about 0.8 M
      NaCl, the time-resolved emission of both the photoacid and conjugate base can be
      quantitatively fitted by our diffusion-assisted geminate recombination model. In
      this concentration range, the proton transfer and geminate recombination rate
      constants are almost independent of the salt concentrations whereas the proton
      diffusion constant decreases as the salt concentration increases. At higher salt
      concentrations, the proton-transfer rate constant decreases while the
      recombination rate constant increases slightly. For the saturated solution of
      MgCl(2) (about 5 M at room temperature), the steady-state emission consists of
      only a single band of the protonated photoacid. Careful examination of the time
      resolved emission of HPTS in the presence of a large concentration of MgCl(2)
      shows that the quality of the fit to the geminate recombination model is rather
      poor and we fail to find adjustable parameters for a good quality fitting. For
      this large concentration range of MgCl(2) we were able to get a good fit of the
      experimental data with a model based on a distribution of proton-transfer rates.
      The model is consistent with an inhomogeneous water environment next to the
      excited HPTS molecule in such concentrated solutions.

PMID- 16640350
TI  - Anomalous excited-state dynamics of lucifer yellow CH in solvents of high
      polarity: evidence for an intramolecular proton transfer.
AB  - The photophysics of the fluorescent probe Lucifer yellow CH has been investigated
      using fluorescence spectroscopic and computational techniques. The nonradiative
      rate is found to pass through a minimum in solvents of intermediate empirical
      polarity. This apparently anomalous behavior is rationalized by considering the
      possibility of predominance of different kinds of nonradiative processes, viz.
      intersystem crossing (ISC) and excited-state proton transfer (ESPT), in solvents
      of low and high empirical polarity, respectively. The feasibility of the proton
      transfer is examined by the structure determined by the density functional theory
      (DFT) calculations. The predicted energy levels based on the time-dependent
      density functional theory (TD-DFT) method in the gas phase identifies the energy
      gap between the S(1) and nearest triplet state to be close enough to facilitate
      ISC. Photophysical investigation in solvent mixtures and in deuterated solvents
      clearly indicates the predominance of the solvent-mediated intramolecular proton
      transfer in the excited state of the fluorophore in protic solvents.

PMID- 16640351
TI  - Photofragmentation of the fluorene cation: I. New experimental procedure using
      sequential multiphoton absorption.
AB  - The hydrogen-loss channel, induced by sequential multiphoton absorption, of the
      vapor-phase fluorene cation was investigated using a supersonic molecular beam
      and a time-of-flight mass spectrometer. The fluorene cation was prepared by
      resonantly enhanced multiphoton ionization. The ultimate goal of this experiment
      is the determination of the evolution of the dissociation rate constant in a wide
      energy range. In this paper, we give a description of the original experimental
      procedure, show that the absorption process is non-Poissonian, and determine the
      absolute photon absorption cross section.

PMID- 16640352
TI  - Photofragmentation of the fluorene cation: II. Determination of the H-loss energy
      dependent rate constant.
AB  - The hydrogen-loss channel, induced by sequential multiphoton absorption, of the
      vapor-phase fluorene cation was investigated using a pulsed supersonic molecular
      beam, a time-of-flight mass spectrometer, and pulsed nanosecond lasers. Our new
      method leads to the determination of the absolute absorption cross section. Its
      attenuation with the number of absorbed photons has been approximated by means of
      statistical models. A model-free determination of the evolution of the
      dissociation rate constant in a relatively large energy range was obtained by
      solving the set of coupled differential kinetic equations numerically. Particular
      attention was focused on the data analysis techniques. The free fit of these rate
      constants is close to the photothermodissociation statistical model, but shows a
      discrepancy with the Rice and Ramsperger and Kassel model mainly at high energy.
      The resulting activation energy is in agreement with both that deduced from the
      ab initio calculations and that from the tight-binding energy potential surface
      model.

PMID- 16640353
TI  - Spectroscopic characterization of peroxynitrous acid in cis-perp configurations.
AB  - This paper presents experimental evidence, supported by two-dimensional
      theoretical calculations, that HOONO can be observed in cis-perp (cp)
      configurations in a pulsed supersonic expansion. The spectral properties
      (transition frequency, rotational constants, and transition type) of OH overtone
      transitions originating from a state with predominately cp character are
      predicted theoretically and compared with those associated with a weak feature at
      6996.2 cm(-1) observed experimentally using infrared action spectroscopy. This
      spectral feature is attributed to HOONO in cp configurations based on its
      vibrational frequency, rotational band contour, and resultant OH product state
      distribution.

PMID- 16640354
TI  - Resonance Raman spectrum of the solvated electron in methanol: simulation within
      a cluster model.
AB  - The microsolvation of the CH(3)OH(2) hypervalent radical in methanol clusters has
      been investigated by density functional theory. It is shown that the CH(3)OH(2)
      radical spontaneously decomposes within methanol clusters into protonated
      methanol and a localized solvated electron cloud. The geometric and electronic
      structures of these clusters as well as their vibrational frequencies have been
      characterized. Resonance Raman intensities, associated with the s --> p
      transition of the unpaired electron, have been estimated for CH(3)OH(2)M(n) (M =
      CH(3)OH, n = 1-3) clusters. It is shown that with increasing cluster size the
      simulated spectra converge toward the resonance Raman spectrum of the solvated
      electron in methanol measured recently by Tauber and Mathies (J. Am. Chem. Soc.
      2004, 126, 3414). The results suggest that CH(3)OH(2)M(n) clusters are useful
      finite-size model systems for the computational investigation of the
      spectroscopic properties of the solvated electron in liquid methanol.

PMID- 16640355
TI  - High-resolution infrared spectroscopy of HCN-Znn (n = 1-4) clusters: structure
      determination and comparisons with theory.
AB  - High-resolution infrared laser spectroscopy has been used to obtain rotationally
      resolved spectra of HCN-Zn(n) (n = 1-4) complexes formed in helium nanodroplets.
      In the present study the droplets passed through a metal oven, where the zinc
      vapor pressure was adjusted until one or more atoms were captured by the
      droplets. A second pickup cell was then used to dope the droplets with a single
      HCN molecule. Rotationally resolved infrared spectra are obtained for all of
      these complexes, providing valuable information concerning their structures.
      Stark spectra are reported and used to determine the corresponding permanent
      electric dipole moments. Ab initio calculations are also reported for these
      complexes for comparison with the experimental results.

PMID- 16640356
TI  - An ab initio study of the absorption spectra of indirubin, isoindigo, and related
      derivatives.
AB  - The UV/visible spectra of a series of indirubin, isoindigo, and other
      indigo/thioindigo related dyes have been evaluated in various solvent
      environments by using the time-dependent density functional theory in conjunction
      with the polarizable continuum model. Even for molecules of the same family,
      significant differences in the excitation processes have been noted. Two hybrid
      functionals have been selected: B3LYP and PBE0. For a set of the 50 selected
      molecular cases, both functionals provide accurate lambda(max), with mean
      absolute deviations limited to 0.1 eV. Actually, isoindigo is the main
      challenging series, with systematically underestimated excitation energies, due
      to the different nature of the excitation process. In most cases, we found that
      PBE0 is more efficient in reproducing the experimental values than B3LYP for
      sulfur-containing dyes not featuring internal hydrogen bonds, the reverse
      assertion being also true. In addition, the spectra of a series of unknown dyes
      have been predicted.

PMID- 16640357
TI  - Infrared spectroscopic and density functional theory studies on the CO
      dissociation by scandium and yttrium dimers.
AB  - Reactions of laser-ablated scandium and yttrium atoms with dilute carbon monoxide
      molecules in solid argon have been investigated using matrix-isolation infrared
      spectroscopy. On the basis of the results of the isotopic substitution, the
      change of laser power and CO concentration and the comparison with density
      functional theory (DFT) calculations, the absorption at 1193.4 cm(-1) is assigned
      to the C-O stretching vibration of the Sc(2)[eta(2)(mu(2)-C,O)] molecule, which
      has a single bridging CO that is tilted to the side. This CO-activated molecule
      undergoes ultraviolet-visible photoinduced rearrangement to the CO-dissociated
      molecule, c-Sc(2)(mu-C)(mu-O). The cyclic c-Sc(2)(mu-C)(mu-O) molecule has a
      bridging carbon on one side of the Sc(2) unit and a bridging oxygen on the other.
      The analogous Y(2)[eta(2)(mu(2)-C,O)] molecule has not been observed, but the CO
      dissociated c-Y(2)(mu-C)(muO) molecule has been observed in the Y + CO
      experiments. DFT calculations of the geometry structures, vibrational
      frequencies, and IR intensities strongly support the assignments. The CO
      activation mechanism has also been discussed. Our experimental and theoretical
      results schematically depict an activation process to CO dissociation.

PMID- 16640358
TI  - Singlet and triplet excited-state interactions and photochemical reactivity of
      phenyleneethynylene oligomers.
AB  - The rigid rodlike character of phenyleneethynylenes and their ability to
      communicate charge/excitation energy over long distances have made them useful as
      molecular linkers in the light energy harvesting assemblies and molecular
      electronics devices. These linker molecules themselves possess rich
      photochemistry as evident from the relatively large yields of the excited singlet
      (0.5-0.66) and triplet (0.4-0.5) states of two model oligomers, 1,4
      bis(phenylethynyl)-2,5-bis(hexyloxy)benzene (OPE-1) and 1,4-bis((4
      phenylethynyl)phenylethynyl)-2,5-bis(hexyloxy)benzene (OPE-2). In particular, the
      long-lived triplet excited state is capable of undergoing deactivation by self
      quenching processes such as ground-state quenching and triplet-triplet (T-T)
      annihilation. The T-T annihilation occurs with a nearly diffusion-controlled rate
      (approximately 2 x 10(9) M(-1) s(-1)), and ground-state quenching occurs with a
      rate constant of approximately 6 x 10(7) M(-1) s(-1). The electron transfer from
      the excited OPE-1 and OPE-2 to benzoquinone as characterized from the transient
      absorption spectroscopy illustrates the ability of these molecules to shuttle the
      electrons to acceptor moieties. In addition, pulse radiolysis experiments confirm
      the spectroscopic fingerprint of the cation radical (or "trapped hole") with
      absorption bands in the 500-600 nm region.

PMID- 16640359
TI  - Studies of the inner reorganization energies of the cation radicals of 1,4
      bis(dimethylamino)benzene, 9,10-bis(dimethylamino)anthracene, and 3,6
      bis(dimethylamino)durene by photoelectron spectroscopy and reinterpretation of
      the mechanism of the electrochemical oxidation of the parent diamines.
AB  - The inner reorganization energy of the cation radical of 1,4
      bis(dimethylamino)benzene, 1, has been determined to be 0.72 +/- 0.02 eV by means
      of gas-phase photoelectron spectroscopy (PES). PES studies of 9,10
      bis(dimethylamino)anthracene, 2, and 3,6-bis(dimethylamino)durene, 3, demonstrate
      that their reorganization energies are smaller than that of 1. The effect of
      lowering the inner reorganization energy on the rate constant for an
      electrochemical electron-transfer reaction is to increase the electron-transfer
      rate constant, k(s). However, voltammetric studies of the two-electron oxidation
      of 2 and 3 indicate that the values of k(s) for each step are smaller than those
      for 1, in contradistinction to the measured differences in reorganization
      energies. The voltammetric studies of 2 and 3 were reinterpreted according to a
      mechanism in which each step of oxidation was written as a two-step process,
      electron transfer with a small inner reorganization energy plus a chemical step
      of structural change. The agreement of simulations according to this mechanism
      with the experimental data was excellent. The new reaction scheme eliminated some
      suspicious features previously obtained with an analysis where electron transfer
      and structural change were considered to be concerted. In particular, all
      electron-transfer coefficients (alpha) were close to one-half, whereas the
      earlier treatment produced values of alpha much larger or smaller than one-half.

PMID- 16640360
TI  - An EPR study of the C-O bond activation of 1,2-epoxybutane by ground-state Al
      atoms.
AB  - Group 13 metal atoms react with ethers under matrix isolation conditions to give
      a number of interesting products. This work has been extended to include the
      reaction of Al atoms with 1,2-epoxybutane (CH(3)CH(2)H(2)) and its isotopomers,
      1,2-epoxybutane-1,1-d(2) (CH(3)CH(2)D(2)) and 1,2-epoxybutane-2-d(1)
      (CH(3)CH(2)H(2)). The paramagnetic species generated in the reaction have been
      studied by electron paramagnetic resonance (EPR) spectroscopy. Two divalent Al
      insertion products were spontaneously formed. Species A, with the magnetic
      parameters a(Al) = 855 MHz, a(H)(1) = 28.8 MHz, a(H)(2) = 13.6 MHz, and g =
      2.0014, is the C(1)-O insertion radical CH(3)CH(2). Species B, thought to result
      from the insertion of Al atoms into the C(2)-O bond, CH(3)CH(2), has the magnetic
      parameters g = 2.0003, a(Al) = 739 MHz, a(H)(1) = 15.1 MHz, a(H)(2) = 18.5 MHz,
      and a(H)(1) = 37.8 MHz. Support for these assignments was obtained by comparing
      the experimental values of the Al and H hyperfine interaction (hfi) with those
      calculated using a DFT method. At temperatures < 150 K, there is evidence for the
      formation of the alkyl radical CH(3)CH(2)CH(O(-))CH(2)* due to ring opening at
      the C(1)-O bond, while at higher temperatures a radical with magnetic parameters
      similar to those reported for 1-methallyl was detected.

PMID- 16640361
TI  - Photophysical processes involved within the anisole-thioindoxyl dyad system.
AB  - The photophysical properties and the nature of the photoinduced electron transfer
      (PET) reactions within a synthesized anisole (A)-thioindoxyl (T) dyad system
      (24MBTO) have been studied by electrochemical, steady-state, and time-resolved
      spectroscopic techniques. Computations on the dyad were performed both in gas
      phase as well as solvent environment by TD-DFT method with B3LYP density
      function. The geometry optimization calculation of 24MBTO was done by 6-311G(d,p)
      basis function set implemented in the Gaussian package. The theoretical values of
      singlet vertical excitation energies were found to correlate well with the
      experimentally observed ones. The electrochemical measurements indicate the
      possibility of occurrence of PET reactions within 24MBTO between the linked redox
      centers A and T. Both steady-state and time-resolved spectroscopic measurements
      on the novel synthesized 24MBTO dyad demonstrate the formations of the two types
      of isomeric species: Z- and E- forms, resulted from the charge separation
      reactions. From the detailed studies it reveals that the present thioaurone may
      behave as a versatile photoswitchable system. It has been hinted that the loss
      process (charge recombination) within 24MBTO could possibly be prevented by
      incorporating it within the hydrophobic cavity of beta-cyclodextrin (betaCD).

PMID- 16640362
TI  - Conformational stability from temperature-dependent fourier transform infrared
      spectra of noble gas solutions, r0 structural parameters, and barriers to
      internal rotation for ethylamine.
AB  - Variable temperature (-55 to -145 degrees C) studies of the infrared spectra
      (3500 to 100 cm(-1)) of ethylamine, CH(3)CH(2)NH(2), dissolved in liquid krypton
      and/or xenon have been recorded. From these data, the enthalpy differences have
      been determined to be 54 +/- 4 cm(-1) (0.65 +/- 0.05 kJ/mol), with the trans
      conformer (methyl group relative to the lone pair of electrons on nitrogen) being
      the more stable form. It is estimated that there is 61 +/- 1% of the doubly
      degenerate gauche form present at ambient temperature. The conformational
      energetics have been calculated with the Moller-Plesset perturbation method to
      the second order (MP2(full)) and the fourth order (MP4(SDTQ)) as well as with
      density functional theory by the B3LYP method utilizing a variety of basis sets.
      Basis sets with diffuse functions lead to incorrect prediction of the
      conformational stability. On the basis of the frequencies of the torsional
      transitions along with the determined experimental enthalpy difference and gauche
      dihedral angle, the potential function governing conformational interchange has
      been obtained, and the determined Fourier cosine coefficients are V(1) = -207 +/-
      48, V(2) = 320 +/- 67, V(3) = 1072 +/- 25, V(4) = 55 +/- 11, and V(5) = -96 +/-
      28 cm(-1), with a trans-to-gauche barrier of 1286 cm(-1), and a gauche-to-gauche
      barrier of 715 cm(-1). The 3-fold methyl rotational barriers have been determined
      to be 1241 +/- 4 and 1281 +/- 10 cm(-1) for the gauche and trans conformers,
      respectively. By utilizing the previously reported microwave rotational constants
      combined with the structural parameters predicted at the MP2(full)/6-311+ G(d,p)
      level, adjusted r(0) structural parameters have been obtained. A complete
      vibrational assignment is given for the trans conformer, which is supported by
      normal coordinate calculations utilizing scaled force constants from ab initio
      B3LYP/6-311++G(3df,3pd) calculations. Proposed assignments are also made for the
      fundamentals of the gauche conformer. The results of these spectroscopic and
      theoretical studies are discussed and compared to the corresponding results for
      similar molecules.

PMID- 16640363
TI  - Bis(trifluoroaceto) disulfide (CF3C(O)OSSOC(O)CF3): a HeI photoelectron
      spectroscopy and theoretical study.
AB  - Bis(trifluoroaceto) disulfide CF(3)C(O)OSSOC(O)CF(3) was prepared and studied by
      Raman, photoelectron spectroscopy (PES), and theoretical calculations. This
      molecule exhibits gauche conformation with both C=O groups cis to the S-S bond;
      the structure of the OSSO moiety is characterized by dihedral angle delta(OSSO) =
      -95.1 degrees due to the sulfur-sulfur lone pair interactions. The contracted S-S
      bond (1.979 Angstroms) and relatively high rotational barrier (19.29 kcal mol(-1)
      at the B3LYP/6-31G level) of the delta(OSSO) indicate the partial resonance
      induced double bond character in this molecule. After ionization, the ground
      cationic-radical form of CF(3)C(O)OSSOC(O)CF(3)(*+) adopts a trans planar main
      atom structure (delta(OSSO) = 180 degrees and delta(OCOS) = 0 degrees ) with
      C(2)(h) symmetry. The S-S bond elongates to 2.054 Angstroms, while the S-O bond
      shortens from 1.755 Angstroms in neutral form to 1.684 Angstroms in its
      corresponding cationic-radical form. The adiabatic ionization energy of 9.91 eV
      was obtained accordingly. The first two HOMOs correspond to the electrons mainly
      localized on the sulfur 3p lone pair MOs: 3ppi {36a (n(A)(S))](-1) and 3ppi [35b
      (n(B)(S), n(B)(O(C)(=)(O)))](-1), with an experimental energy separation of 0.16
      eV. The first vertical ionization energy is determined to be 10.81 eV.

PMID- 16640364
TI  - Thermodynamic models of aqueous solutions containing inorganic electrolytes and
      dicarboxylic acids at 298.15 K. 1. The acids as nondissociating components.
AB  - Atmospheric aerosols contain a significant fraction of water-soluble organic
      compounds, including dicarboxylic acids. Water activities at approximately 298.15
      K (including data for highly supersaturated solutions) of oxalic, malonic,
      succinic, glutaric, maleic, malic, and methyl succinic acids are first correlated
      as a function of concentration, treating the acids as nondissociating components.
      Methods proposed by Clegg et al. (J. Aerosol. Sci. 2001, 32, 713-738), and by
      Clegg and Seinfeld (J. Phys. Chem. A 2004, 108, 1008-1017) for estimating water
      activities and solute activity coefficients in aqueous mixtures containing both
      electrolytes and uncharged solutes are then evaluated from comparisons with
      literature data. These data include water activities, solubilities, and
      determinations of the eutonic points of solutions containing up to five acids,
      and solutions containing one or more acids and the salts (NH(4))(2)SO(4),
      NH(4)NO(3), or NaCl. The extended Zdanovskii-Stokes-Robinson approach of Clegg
      and Seinfeld yields the more accurate predictions for aqueous mixtures containing
      dicarboxylic acids only, and for aqueous mixtures of the acids and salts (though
      by a lesser margin). A number of hybrid modeling approaches, which contain
      elements of both methods, are outlined.

PMID- 16640365
TI  - Thermodynamic models of aqueous solutions containing inorganic electrolytes and
      dicarboxylic acids at 298.15 K. 2. Systems including dissociation equilibria.
AB  - Atmospheric aerosols contain a significant fraction of water-soluble organic
      compounds, including dicarboxylic acids. Pitzer activity coefficient models are
      developed, using a wide range of data at 298.15 K, for the following systems
      containing succinic acid (H(2)Succ) and/or succinate salts: [H(+), Li(+), Na(+),
      K(+), Rb(+), Cs(+)]Cl(-)-H(2)Succ-H(2)O, HNO(3)-H(2)Succ-H(2)O, H(+)-NH(4)(+)
      HSucc(-)-Succ(2-)-NH(3)-H(2)Succ-H(2)O, NH(4)Cl-(NH(4))(2)Succ-H(2)O, H(+)-Na(+)
      HSucc(-)-Succ(2-)-Cl(-)-H(2)Succ-H(2)O, NH(4)NO(3)-H(2)Succ-H(2)O, and H(2)SO(4)
      H(2)Succ-H(2)O. The above compositions are given in terms of ions in the cases
      where acid dissociation was considered. Pitzer models were also developed for the
      following systems containing malonic acid (H(2)Malo): H(+)-Na(+)-HMalo(-)-Malo(2
      )-Cl(-)-H(2)Malo-H(2)O, and H(2)Malo-H(2)SO(4)-H(2)O. The models are used to
      evaluate the extended Zdanovskii-Stokes-Robinson (ZSR) model proposed by Clegg
      and Seinfeld (J. Phys. Chem. A 2004, 108, 1008-1017) for calculating water and
      solute activities in solutions in which dissociation equilibria occur. The ZSR
      model yields satisfactory results only for systems that contain moderate to high
      concentrations of (nondissociating) supporting electrolyte. A practical modeling
      scheme is proposed for aqueous atmospheric aerosols containing both electrolytes
      and dissociating (organic) nonelectrolytes.

PMID- 16640366
TI  - Transannular distance dependence of stabilization energy of the intramolecular
      dimer radical cation of cyclophanes.
AB  - The intramolecular dimer radical cation and charge-transfer complex of various
      cyclophanes were investigated by using pulse radiolysis measurements. The charge
      resonance band due to the dimer radical cation of cyclophanes appeared in the
      near-IR region, which showed a blue-shift as the distance between the two benzene
      rings of cyclophane decreased. The stabilization energy of the dimer radical
      cation, which was estimated from the peak position of the charge resonance band,
      was explained by the exchange interaction, while the substituent effect was
      small. The absorption peak of the charge-transfer complex with chlorine atom also
      showed the shift in accordance with the oxidation potential of cyclophanes.

PMID- 16640367
TI  - Guanine alkylation by ethylene oxide: calculation of chemical reactivity.
AB  - In this paper we report on calculations of the activation free energy for a
      chemical reaction between ethylene oxide and guanine. Ethylene oxide is
      biologically relevant per se and is also a model compound for numerous ultimate
      carcinogens. Calculations were performed on the medium-high ab initio, DFT, and
      semiempirical MO levels. Effects of solvation were considered using the Langevine
      dipole method and solvent reaction field method of Tomasi and co-workers. The
      calculated activation free energies are in reasonable agreement with the
      experimental value.

PMID- 16640368
TI  - Do NAD and NAT form in liquid stratospheric aerosols by pseudoheterogeneous
      nucleation?
AB  - Laboratory data of the freezing of nitric acid hydrates (NAD, NAT) from
      HNO(3)/H(2)O and HNO(3)/H(2)SO(4)/H(2)O solution droplets have been evaluated
      with respect to a "pseudoheterogeneous" (surface-induced) nucleation mechanism of
      NAD and NAT, which has been argued to possibly lead to the formation of polar
      stratospheric clouds (PSCs). In addition, a parametrization of
      pseudoheterogeneous nucleation of NAD and NAT suggested recently (Tabazadeh et
      al. J. Phys. Chem. A 2002, 106, 10238-10246) has been analyzed, showing that this
      parametrization should not be used in stratospheric modeling studies. The
      analysis of several laboratory data sets yields an upper limit of the
      pseudoheterogeneous nucleation rate coefficient of NAD of 2.2 x 10(-5) cm(-2) s(
      1). In contrast, the upper limit of the pseudoheterogeneous nucleation rate
      coefficient of NAT could not be constrained satisfactorily, since formation of
      NAT has not been observed at stratospheric conditions in laboratory experiments
      applying small droplets. Maximum NAD production rates of 9.6 x 10(-9) cm(-3)
      (air) h(-1) in the stratosphere have been estimated assuming a
      pseudoheterogeneous nucleation mechanism that is constrained by the experimental
      observations. If maximum NAD supersaturation persisted for 4 weeks in the polar
      stratosphere the corresponding NAD particle number densities are estimated to be
      about 6 x 10(-6) cm(-3). These particle number densities are 3 orders of
      magnitude lower than particle number densities recently observed in the
      stratosphere. In conclusion, on the basis of laboratory data it is found that a
      pseudoheterogeneous nucleation mechanism is not sufficient to explain recent
      observations of large nitric acid containing particles in the polar stratosphere.

PMID- 16640369
TI  - Oxidation of gas-phase protactinium ions, Pa+ and Pa2+: formation and properties
      of PaO2(2+)(g), protactinyl.
AB  - Oxidation reactions of bare and ligated, monopositive, and dipositive Pa ions in
      the gas phase were studied by Fourier transform ion cyclotron resonance mass
      spectrometry. Seven oxidants were employed, ranging from the thermodynamically
      robust N(2)O to the relatively weak CH(2)O-all oxidized Pa(+) to PaO(+) and
      PaO(+) to PaO(2)(+). On the basis of experimental observations, it was
      established that D[Pa(+)-O] and D[OPa(+)-O] > or = 751 kJ mol(-1). Estimates for
      D[Pa(+)-O], D[OPa(+)-O], IE[PaO], and IE[PaO(2)] were also obtained. The seven
      oxidants reacted with Pa(2+) to produce PaO(2+), indicating that D[Pa(2+)-O] > or
      = 751 kJ mol(-1). A particularly notable finding was the oxidation of PaO(2+) by
      N(2)O to PaO(2)(2+), a species, which formally comprises Pa(VI). Collision
      induced dissociation of PaO(2)(2+) suggested the protactinyl connectivity, {O-Pa
      O}(2+). The experimentally determined IE[PaO(2)(+)] approximately 16.6 eV is in
      agreement with self-consistent-field and configuration interaction calculations
      for PaO(2)(+) and PaO(2)(2+). These calculations provide insights into the
      electronic structures of these ions and indicate the participation of 5f orbitals
      in bonding and a partial "6p hole" in the case of protactinyl. It was found that
      PaO(2)(2+) catalyzes the oxidation of CO by N(2)O-such O atom transport via a
      dipositive metal oxide ion is distinctive. It was also observed that PaO(2)(2+)
      is capable of activating H(2) to form the stable PaO(2)H(2+) ion.

PMID- 16640370
TI  - Isomeric effects in the gas-phase reactions of dichloroethene, C2H2CL2, with a
      series of cations.
AB  - A study of the reactions of a series of gas-phase cations (NH(4)(+), H(3)O(+),
      SF(3)(+), CF(3)(+), CF(+), SF(5)(+), SF(2)(+), SF(+), CF(2)(+), SF(4)(+),
      O(2)(+), Xe(+), N(2)O(+), CO(2)(+), Kr(+), CO(+), N(+), N(2)(+), Ar(+), F(+), and
      Ne(+)) with the three structural isomers of dichloroethene, i.e., 1,1
      C(2)H(2)Cl(2), cis-1,2-C(2)H(2)Cl(2), and trans-1,2-C(2)H(2)Cl(2) is reported.
      The recombination energy (RE) of these ions spans the range of 4.7-21.6 eV.
      Reaction rate coefficients and product branching ratios have been measured at 298
      K in a selected ion flow tube (SIFT). Collisional rate coefficients are
      calculated by modified average dipole orientation (MADO) theory and compared with
      experimental data. Thermochemistry and mass balance have been used to predict the
      most feasible neutral products. Threshold photoelectron-photoion coincidence
      spectra have also been obtained for the three isomers of C(2)H(2)Cl(2) with
      photon energies in the range of 10-23 eV. The fragment ion branching ratios have
      been compared with those of the flow tube study to determine the importance of
      long-range charge transfer. A strong influence of the isomeric structure of
      dichloroethene on the products of ion-molecule reactions has been observed for
      H(3)O(+), CF(3)(+), and CF(+). For 1,1-C(2)H(2)Cl(2) the reaction with H(3)O(+)
      proceeds at the collisional rate with the only ionic product being 1,1
      C(2)H(2)Cl(2)H(+). However, the same reaction yields two more ionic products in
      the case of cis-1,2- and trans-1,2-C(2)H(2)Cl(2), but only proceeds with 14% and
      18% efficiency, respectively. The CF(3)(+) reaction proceeds with 56-80%
      efficiency, the only ionic product for 1,1-C(2)H(2)Cl(2) being C(2)H(2)Cl(+)
      formed via Cl(-) abstraction, whereas the only ionic product for both 1,2-isomers
      is CHCl(2)(+) corresponding to a breaking of the C=C double bond. Less profound
      isomeric effects, but still resulting in different products for 1,1- and 1,2
      C(2)H(2)Cl(2) isomers, have been found in the reactions of SF(+), CO(2)(+),
      CO(+), N(2)(+), and Ar(+). Although these five ions have REs above the ionization
      energy (IE) of any of the C(2)H(2)Cl(2) isomers, and hence the threshold for long
      range charge transfer, the results suggest that the formation of a collision
      complex at short range between these ions and C(2)H(2)Cl(2) is responsible for
      the observed effects.

PMID- 16640371
TI  - Pathways and rate coefficients for the decomposition of vinoxy and acetyl
      radicals.
AB  - The potential in the vicinity of the stationary points on the surface for the
      decomposition of ground-state vinoxy and acetyl radicals has been calculated
      using the RQCISD(T) method extrapolated to the infinite-basis set limit. Rate
      coefficients for the decomposition pathways of these two radicals were computed
      using the master equation and variational transition state theory. Agreement
      between our calculated rate coefficients for H + CH(2)CO <--> CH(3) + CO and
      experimental data is very good, without the need for empirical adjustments to the
      ab initio energy barriers. Multireference configuration-interaction calculations
      indicate two competitive channels for vinoxy decomposition, with the channel
      leading to H + CH(2)CO being preferred at photodissociation energies. However, at
      typical combustion conditions, vinoxy decomposes primarily to CO and methyl. In
      contrast, decomposition of acetyl shows only one decomposition channel, leading
      to CO and methyl. The implications of a low-lying exit channel for the
      calculation of theoretical rate coefficients are discussed briefly.

PMID- 16640372
TI  - A combined experimental and theoretical study on the conformational behavior of a
      calix[6]arene.
AB  - An experimental and theoretical study on the conformational behavior of the 1,3,5
      OMe-2,4,6-OCH(2)CONHOH-p-tert-butylcalix[6]arene has been carried out. In
      particular, semiempirical (AM1) and density functional theory (DFT) calculations
      have been performed in order to identify the possible conformers. The obtained
      results show that the cone structure is the most stable conformer at any level of
      theory, even if significant differences have been obtained for the other species.
      The inclusion of solvent effect, through a continuum model, also points out the
      relevant role played by the solvent in the stabilization of the cone structure in
      solution. These latter results have been confirmed by NMR experiments, which
      clearly show the presence of only the cone conformer in a polar solvent, such as
      DMSO. Finally, (1)H and (13)C NMR spectra on model systems, i.e., two successive
      phenol rings (Ar(1)-CH(2)-Ar(2)), have been computed at the DFT level and
      compared with the experimental spectra of the complete molecule. The results show
      an overall good agreement with the experimental data, thus leading to an
      unambiguous assignment of the experimental spectra.

PMID- 16640373
TI  - Atomistic molecular modeling of the effect of chromophore concentration on the
      electro-optic coefficient in nonlinear optical polymers.
AB  - We employ fully atomistic molecular modeling to investigate the concentration
      dependence of the electro-optic coefficient of two guest-host polymer composites.
      Using classical molecular dynamics, we record the time-evolution of the guest
      host system under the application of an external electric field. Through analysis
      of the orientation of the nonlinear optical chromophores in the guest-host
      composite with respect to the direction of the external electric field, we
      calculate the orientational parameter N < cos(3)theta >, with N being the number
      density of chromophores in the composite. This parameter is directly proportional
      to the electro-optic coefficient. We find agreement between the concentration
      dependence of the electro-optic coefficient calculated through our simulation and
      that from experimental data and also from Monte Carlo models.

PMID- 16640374
TI  - Enthalpies of hydration of N-methylacetamide by one, two, and three waters and
      the effect upon the C=O stretching frequency. An Ab initio DFT study.
AB  - DFT calculations at the B3LYP/D95++(d,p) level of clusters of N-methylacetamide
      (NMA) with one, two, and three waters that were geometrically optimized on the
      counterpoise-corrected potential energy surfaces show that the gas-phase enthalpy
      of the interactions of NMA with three waters is -14.11 kcal/mol. Since the
      interactions between the three waters is 0.99 kcal/mol, the interaction enthalpy
      would become -15.10 if these interactions were subtracted. The internal geometry
      of the NMA molecule is sensitive to the degree of hydration, as are the H-bond
      lengths. Changes in the internal bond lengths with degree of hydration are
      approximately additive. The calculated C=O stretching frequencies correlate
      extremely well with the calculated C=O bond lengths, which suggests that the
      solvent effect upon this stretch could not be a purely electrostatic interaction.
      The calculated C=O stretch for NMA solvated by three waters in the gas phase
      agrees very well with that experimentally observed in aqueous solution.

PMID- 16640375
TI  - Ab initio MO analysis of interaction paths between radicals in ferromagnetic
      organic systems.
AB  - Interaction path analyses for pi-conjugated organic systems were performed at the
      ab initio molecular orbital level to examine the relationship between inter
      radical interactions and the high-spin stability of the system. It was found that
      the high-spin stability results from through-bond interactions between radicals,
      not from through-space interactions, in relation to the stabilization of a low
      spin state due to the effects of electron correlation. L(ij)(min) value for
      estimating the mixing of nonbonding molecular orbitals well predicted the
      relationship between the through-bond interactions and the high-spin stability.
      Furthermore, molecular orbital calculations revealed that the all-trans type
      interaction path between radicals produces long-range exchange interactions, and
      the additivity of high-spin stability is observed by keeping short-range through
      bond interaction paths.

PMID- 16640376
TI  - Larger water clusters with edges and corners on their way to ice: structural
      trends elucidated with an improved parallel evolutionary algorithm.
AB  - For the difficult task of finding global minimum energy structures for molecular
      clusters of nontrivial size, we present a highly efficient parallel
      implementation of an evolutionary algorithm. By completely abandoning the
      traditional concept of generations and by replacing it with a less rigid pool
      concept, we have managed to eliminate serial bottlenecks completely and can
      operate the algorithm efficiently on an arbitrary number of parallel processes.
      Nevertheless, our new algorithm still realizes all of the main features of our
      old, successful implementation. First tests of the new algorithm are shown for
      the highly demanding problem of water clusters modeled by a potential with
      flexible, polarizable monomers (TTM2-F). For this problem, our new algorithm not
      only reproduces all of the global minima proposed previously in considerably less
      CPU time but also leads to improved proposals in several cases. These, in turn,
      qualitatively change our earlier predictions concerning the transitions from all
      surface structures to cages with a single interior molecule, and from one to two
      interior molecules. Furthermore, we compare preliminary results up to n = 105
      with locally optimized cuts from several ice modifications. This comparison
      indicates that relaxed ice structures may start to be competitive already at
      cluster sizes above n = 90.

PMID- 16640377
TI  - Intertrimer and intratrimer metallophilic and excimeric bonding in the ground and
      phosphorescent States of trinuclear coinage metal pyrazolates: a computational
      study.
AB  - The interactions present in cyclic trinuclear coinage metal pyrazolates were
      studied computationally. Cuprophilic interaction was found to bind the singlet
      ground state of the dimer of trimers [[Cu(Pz)](3)](2), overcoming electrostatic
      repulsion. The large variation in intertrimer separations found in the literature
      for coinage metal pyrazolates is consistent with the relatively weak
      metallophilic interaction. The emissive triplet excited-state geometry of
      [[M(Pz)](3)](2) is predicted by density functional calculations to show major
      geometric distortion caused by Jahn-Teller instability and excimeric M-M bonding.
      Large calculated Stokes' shifts, which are also observed for experimental models,
      are consistent with significant excited-state distortions for these materials.
      The major finding derived from the present study is that the intertrimer M...M
      contraction in the emissive T(1) state is much more than the intratrimer
      contraction in all [[M(Pz)](3)](2) models, giving rise to a lower T(1) --> S(0)
      phosphorescence energy in these models than in analogous monomer-of-trimer
      models. The observations made here point to a great potential for rationally
      tuning the emission properties of trinuclear coinage metal complexes through
      choice of the metal and ligands.

PMID- 16640378
TI  - A gas- and condensed-phase density functional study of donor-acceptor complexes
      of sulfur trioxide.
AB  - A series of donor-acceptor complexes containing sulfur trioxide have been studied
      in the gas and condensed phases using density functional theory. The condensed
      phase is represented using the polarizable continuum model. The systems
      investigated include complexes of nitrogen-containing donor molecules,
      (CH(3))(n)H(3-n)N (n = 0-3), with SO(3) and complexes of oxygen-containing donor
      molecules, (CH(3))(m)H(2-m)O (m = 0-2), with SO(3). Significant differences are
      observed between the gas- and condensed-phase properties of the complexes as a
      result of the ability of the condensed-phase medium to support higher charge
      separation between the donor and acceptor. The gas/condensed-phase behavior of
      two nitrogen-containing complexes, (CH(3))H(2)N-SO(3) and (CH(3))(2)HN-SO(3), has
      been investigated for the first time. These complexes exhibit properties
      intermediate to the previously observed H(3)N-SO(3) and (CH(3))(3)N-SO(3)
      complexes. Systematic trends in the gas- and condensed-phase structure and
      properties have been observed as methyl groups are added to the donor molecule.
      In addition, two oxygen-containing complexes, CH(3)OH-SO(3) and (CH(3))(2)O
      SO(3), have been characterized for the first time. The differences between the
      gas- and condensed-phase properties of the oxygen-containing complexes are, in
      many cases, larger than those of the nitrogen-containing complexes, and therefore
      they represent an intriguing new class of complexes for potential experimental
      observation. Finally, a strong correlation between the charge transfer and
      binding energy has been obtained for both the nitrogen- and oxygen-containing
      complexes of sulfur trioxide.

PMID- 16640379
TI  - Effect of particle size on the oxidizability of platinum clusters.
AB  - The catalytic properties of transition metal particles often depend crucially on
      their chemical environment, but so far, little is known about how the effects of
      the environment vary with particle size, especially for clusters consisting of
      only a few atoms. To gain insight into this topic, we have studied the oxygen
      affinity of free Pt(x) clusters as a function of cluster size (x = 1, 2, 3, 4, 5,
      and 10) using density functional theory (DFT) calculations (GGA-PW91). DFT-based
      Nose-Hoover molecular dynamics has been used to explore the configuration space
      of the Pt(x)O(x) and Pt(x)O(2x) clusters, leading to the discovery of several
      novel Pt-oxide structures. The formation of small Pt-oxide clusters by oxidizing
      the corresponding Pt(x) clusters is found to be significantly more exothermic
      than the formation of bulk Pt-oxides from Pt metal. The exothermicity generally
      increases as cluster size decreases but exhibits strongly nonlinear dependence on
      the cluster size. The nanoclusters are also structurally distinct from the bulk
      oxides and prefer one- and two-dimensional chain and ringlike shapes. These
      findings help elucidate the oxidation behavior of Pt nanoclusters and lay the
      foundation for understanding the reactivity of Pt nanoclusters in oxidizing
      chemical environments.

PMID- 16640380
TI  - A theoretical study of properties and reactions involving arsenic and selenium
      compounds present in coal combustion flue gases.
AB  - Species of arsenic and selenium thought to be present in coal combustion flue
      gases were studied using density functional theory and a broad range of ab initio
      methods. At each level of theory, the calculated geometries and vibrational
      frequencies of each species as well as the reaction enthalpies of anticipated
      reactions were compared with experimental data where available. Comparisons
      between each calculation are given along with a discussion of the better
      performance of some theoretical calculations for a given species/reaction.

PMID- 16640381
TI  - Direct dynamics study on hydrogen abstraction reaction of CF3CF2CH2OH with OH
      radical.
AB  - The dual-level direct dynamics method has been employed to investigate the H
      abstraction reaction of CF(3)CF(2)CH(2)OH with OH radical, which is predicted to
      have two classes of possible reaction channels caused by different positions of
      hydrogen atom attack. The minimum-energy path is calculated at the B3LYP/6
      311G(d,p) level, and the energetic information is further refined by the MC-QCISD
      method. To compare the structures, the other method MPW1K/6-311G(d,p) is also
      applied to this system. Hydrogen-bonded complexes are presented in the reactant
      and product sides of the three channels, indicating that each reaction may
      proceed via an indirect mechanism. The rate constants for each reaction channel
      are evaluated by canonical variational transition-state theory (CVT) with the
      small-curvature tunneling correction (SCT) over a wide range of temperatures from
      200 to 2000 K. The calculated CVT/SCT rate constants are found to be in good
      agreement with the available experimental values. The result shows that the
      variational effect is small, and in the lower-temperature range, the SCT effect
      is important for each reaction. It is shown that hydrogen abstracted from the 
      CH(2)- position is the major channel, while H-abstraction from the -OH position
      may be neglected with the temperature increasing.

PMID- 16640382
TI  - Interpretation of hydrogen bonding in the weak and strong regions using
      conceptual DFT descriptors.
AB  - Hydrogen bonding is among the most fundamental interactions in biology and
      chemistry, providing an extra stabilization of 1-40 kcal/mol to the molecular
      systems involved. This wide range of stabilization energy underlines the need for
      a general and comprehensive theory that will explain the formation of hydrogen
      bonds. While a simple electrostatic model is adequate to describe the bonding
      patterns in the weak and moderate hydrogen bond regimes, strong hydrogen bonds,
      on the other hand, require a more complete theory due to the appearance of
      covalent interactions. In this study, conceptual DFT tools such as local
      hardness, eta(r) and local softness, s(r), have been used in order to get an
      alternative view on solving this hydrogen-bonding puzzle as described by Gilli et
      al. [J. Mol. Struct. 2000, 552, 1]. A series of both homonuclear and
      heteronuclear resonance-assisted hydrogen bonds of the types O-H...N, N-H...O, N
      H...N, and O-H...O with strength varying from weak to very strong have been
      studied. First of all, DeltaPA and DeltapK(a) values were calculated and
      correlated to the hydrogen bond energy. Then the electrostatic effects were
      examined as hard-hard interactions accessible through molecular electrostatic
      potential, natural population analysis (NPA) charge, and local hardness
      calculations. Finally, secondary soft-soft interaction effects were entered into
      the picture described by the local softness values, providing insight into the
      covalent character of the strong hydrogen bonds.

PMID- 16640383
TI  - EPR theoretical study of local molecular structure and thermal expansion
      coefficient for octahedral Mn2+ centers in zinc fluosilicate.
AB  - A theoretical method for studying the inter-relation between electronic and
      molecular structure has been proposed by diagonalizing the complete energy
      matrices for a d(5) configuration ion in a trigonal ligand field and considering
      the second-order and fourth-order EPR parameters D and (a - F) simultaneously. As
      for ZnSiF(6).6H(2)O:Mn(2+) and ZnSiF(6).6D(2)O:Mn(2+) complex molecules, the
      local lattice distortion and local thermal expansion coefficient for the
      octahedral Mn(2+) centers in zinc fluosilicate have been investigated,
      respectively. The calculations indicate that the local lattice structure around
      an octahedral Mn(2+) center has an expansion distortion, whether the Mn(2+) ion
      is doped in ZnSiF(6).6H(2)O or ZnSiF(6).6D(2)O. Moreover, the total tendency of
      the local lattice expansion distortion will be more and more obvious with the
      temperature rising, apart from some slight variations at T = 60 K for the
      ZnSiF(6).6H(2)O. By simulating the two low-symmetry EPR parameters D and (a - F)
      simultaneously, the local lattice structure parameters R and theta have been
      determined to vary from 2.204 Angstroms to 2.256 Angstroms and from 53.417
      degrees to 52.710 degrees, respectively, in the temperature range 19-297 K for
      ZnSiF(6).6H(2)O:Mn(2+) and to vary from 2.215 Angstroms to 2.255 Angstroms and
      from 53.346 degrees to 52.714 degrees, respectively, in the temperature range 50
      300 K for ZnSiF(6).6D(2)O:Mn(2+). Subsequently the dependence of local thermal
      expansion coefficients on the temperature is studied and the corresponding
      theoretical values of the local thermal expansion coefficients are reported
      firstly. Some characteristics of local thermal expansion coefficients of Mn(2+)
      in ZnSiF(6).6H(2)O:Mn(2+) and ZnSiF(6).6D(2)O:Mn(2+) systems are also analyzed.

PMID- 16640384
TI  - Quantum-chemical predictions of redox potentials of organic anions in dimethyl
      sulfoxide and reevaluation of bond dissociation enthalpies measured by the
      electrochemical methods.
AB  - A first-principle theoretical protocol was developed that could predict the
      absolute pK(a) values of over 250 structurally unrelated compounds in DMSO with a
      precision of 1.4 pK(a) units. On this basis we developed the first theoretical
      protocol that could predict the standard redox potentials of over 250
      structurally unrelated organic anions in DMSO with a precision of 0.11 V. Using
      the two new protocols we systematically reevaluated the bond dissociation
      enthalpies (BDEs) measured previously by the electrochemical methods. It was
      confirmed that for most compounds the empirical equation (BDE = 1.37 pK(HA) +
      23.1E(o) + constant) was valid. The constant in this equation was determined to
      be 74.0 kcal/mol, compared to 73.3 kcal/mol previously reported. Nevertheless,
      for a few compounds the empirical equation could not be used because the
      solvation energy changed dramatically during the bond cleavage, which resulted
      from the extraordinary change of dipole moment during the reaction. In addition,
      we found 40 compounds (mostly oximes and amides) for which the experimental
      values were questionable by over 5 kcal/mol. Further analyses revealed that all
      these questionable BDEs could be explained by one of the three following reasons:
      (1) the experimental pK(a) value is questionable; (2) the experimental redox
      potential is questionable; (3) the solvent effect cannot be neglected. Thus, by
      developing practical theoretical methods and utilizing them to solve realistic
      problems, we hope to demonstrate that ab initio theoretical methods can now be
      developed to make not only reliable, but also useful, predictions for solution
      phase organic chemistry.

PMID- 16640385
TI  - Thermochemistry of the hypobromous and hypochlorous acids, HOBr and HOCl.
AB  - The enthalpies of formation of HOBr and HOCl have been estimated by employing
      coupled cluster theory in conjunction with the correlation consistent basis sets
      and corrections for core-valence, relativistic, and anharmonic effects. We have
      employed three different reactions to estimate the DeltaH(o)(f,298)(HOBr),
      namely, the atomization reaction and two homodesmic reactions. Our best
      estimation is DeltaH(o)(f,298) (HOBr) = -15.3 +/- 0.6 kcal/mol and is very likely
      to lie toward the more negative values. The present value is 1.4 kcal/mol lower
      than the widely used experimental determination of Ruscic and Berkowitz (J. Chem.
      Phys. 1994, 101, 7795), DeltaH(o)(f,298)(HOBr) > -13.93 +/- 0.42 kcal/mol.
      However, it is closer to the more recent measurement of Lock et al. (J. Phys.
      Chem. 1996, 100, 7972), DeltaH(o)(f,298)(HOBr) = -14.8 +/- 1 kcal/mol. In the
      case of HOCl we have determined DeltaH(o)(f,298)(HOCl) = -18.1 +/- 0.3 kcal/mol,
      just in the middle of the two experimental values proposed, -17.8 +/- 0.5
      kcal/mol (JANAF), obtained from equilibrium constant measurements, and -18.36 +/-
      0.03 kcal/mol (Joens, J. A. J. Phys. Chem. A 2001, 105, 11041), determined from
      the measurements of the Cl-OH bond energy. If our conclusions are correct,
      several enthalpies of formation that have been determined by experimental
      chemists, Orlando and Burholder (J. Phys. Chem. 1995, 99, 1143), and theoretical
      chemists, Lee (J. Phys. Chem. 1995, 99, 15074), need to be revised, since a
      larger value was used for DeltaH(o)(f,298)(HOBr). Employing the results obtained
      by Orlando and Burkholder for Br(2)O we propose DeltaH(o)(f,298)(Br(2)O) = 24.9
      +/- 0.6 kcal/mol, and employing Lee's enthalpies of reaction we propose the
      following DeltaH(o)(f,298): for BrBrO, HBrO, ClOBr, ClBrO, BrClO, BrCN, BrNC,
      BrNO, BrON, FOBr, and FBrO, 39.5 +/- 1, 41.0 +/- 1, 22.7 +/- 1.5, 34.2 +/- 1.5,
      40.9 +/- 1.5, 43.7 +/- 1.5, 80.1 +/- 1.5, 22.3 +/- 1, 46.2 +/- 1, 17.3 +/- 1.5,
      and 6.3 +/- 1.5 kcal/mol, respectively. We expect that this work will stimulate
      new experimental measurements of the thermodynamic properties of HOBr and HOCl.

PMID- 16640386
TI  - Evaluation of effective core potentials and basis sets for the prediction of the
      geometries of alkyltin halides.
AB  - A systematic comparison of the optimized geometries of five organotin compounds,
      Cl(n)Sn(CH(3))(4-n), n = 0-4, with the available gas-phase electron diffraction
      results is reported. All optimizations were carried out with the B3LYP density
      functional method. Comparison of 10 basis sets and three effective core
      potentials leads to the conclusion that the combination of the SDB-aug-cc-pVTZ
      basis set and the LANL2 effective core potential for tin, together with the 6
      31G(d,p) basis set for the other atoms, is recommended for the prediction of the
      geometries of organotin compounds.

PMID- 16640387
TI  - Sparkle/AM1 structure modeling of lanthanum (III) and lutetium (III) complexes.
AB  - The sparkle/AM1 model for the quantum chemical prediction of coordination
      polyhedron crystallographic geometries from isolated lanthanide complex ion
      calculations, defined recently for Eu(III), Gd(III), and Tb(III) (Inorg. Chem.
      2005, 44, 3299) is now extended to La(III) and Lu(III). Thus, for each of the
      metal ions we chose a training set of 15 complexes that possess various
      representative ligands of high crystallographic quality (R factor < 0.05
      Angstroms) and oxygen and/or nitrogen as coordinating atoms. In the validation
      procedure we used a set of 60 more La(III) coordination compound structures, as
      well as 15 more Lu(III) coordination compound structures, all of high
      crystallographic quality. For both the 75 La(III) compounds and the 30 Lu(III)
      compounds, the Sparkle/AM1 unsigned mean error, for all interatomic distances
      between the metal ions and the ligand atoms of the first sphere of coordination,
      is 0.08 Angstroms, thus comparable to the accuracy normally achievable by present
      day ab initio/ECP calculations, while being hundreds of times faster.

PMID- 16640388
TI  - Equilibrium geometries and associated energetic properties of mixed metal-silicon
      clusters from global optimization.
AB  - The structural properties of the cluster series Me(m)Si(7-m) (Me = Cu and Li, m <
      or = 6) are studied by density functional theory (DFT) employing a plane wave
      basis. The equilibrium geometries and energetic properties of these clusters are
      obtained by use of the simulated annealing procedure in conjunction with the Nose
      thermostat algorithm. The lowest energy isomer thus obtained is analyzed by
      density functional theory at the B3LYP/6-311+G(d,p) level including all
      electrons. Pentagonal ground state structures derived from the D(5)(h)
      equilibrium geometries of both Si(7) and Cu(7) are obtained for Cu(m)Si(7-m) with
      m < 6. The Li(m)Si(7-m) clusters, in contrast, tend toward adsorption geometries
      where m Li atoms are attached to a Si(7-m)framework with pronounced negative
      charge. For both Li(m)Si(7-m) and Cu(m)Si(7-m), a marked decrease of the energy
      gap is found as the number of metal atom constituents increases.

PMID- 16640389
TI  - Theoretical investigation of the (hyper)polarizabilities of pyrrole homologues
      C4H4XH (X = N, P, As, Sb, Bi). A coupled-cluster and density functional theory
      study.
AB  - Geometries, inversion barriers, static and dynamic electronic and vibrational
      dipole polarizability (alpha), and first (beta) and second (gamma)
      hyperpolarizability of the pyrrole homologues C(4)H(4)XH (X = N, P, As, Sb, Bi)
      have been calculated by Hartree-Fock, Moller-Plesset second-order perturbation
      theory, coupled-cluster theory accounting for singles, doubles, and noniterative
      triple excitations methods, as well as density functional theory using B3LYP and
      PBE1PBE functionals and Sadlej's Pol and 6-311G basis sets. Relativistic effects
      on the heavier homologues stibole and bismole have been taken into account within
      effective core potential approximation. The results show that the electronic
      (hyper)polarizabilities monotonically increase with the atomic number of the
      heteroatom, consistent with the decrease in the molecular hardness. Ring
      planarization reduces the carbon-carbon bond length alternation of the cis
      butadienic unit, enhancing the electronic polarizability values (alpha(e)) by 4
      12% and the (hyper)polarizability values (and gamma(e)) by 30-90%. Pure
      vibrational and zero-point vibrational average contributions to the
      (hyper)polarizabilities have been determined within the clamped nucleus approach.
      In the static limit, the pure vibrational hyperpolarizabilities have a major
      contribution. Anharmonic corrections dominate the pure vibrational
      hyperpolarizabilities of pyrrole, while they are less important for the heavier
      homologues. Static and dynamic electronic response properties of the pyrrole
      homologues are comparable to or larger than the corresponding properties of the
      furan and cyclopentadiene homologue series.

PMID- 16640390
TI  - BAC-MP4 predictions of thermochemistry for gas-phase antimony compounds in the Sb
      H-C-O-Cl system.
AB  - Calibrated by both experimental data and high-level coupled-cluster calculations,
      the BAC-MP4 methodology was applied to 51 SbL(n) (L = H, CH(3), C(2)H(5), Cl, and
      OH, n = 1-5) molecules, providing calculated heats of formation and associated
      thermodynamic parameters. These data identify a linear variation in heats of
      formation with ligand substitution, trends in bond dissociation energies (BDEs)
      with ligand identity [BDE(Sb-C(2)H(5)) < BDE(Sb-CH(3)) < BDE(Sb-H) < BDE(Sb-Cl) <
      BDE(Sb-OH)], and a monotonic decrease in BDE upon successive ligand elimination.
      The linear variation in BDE is consistent with the behavior of other group V
      elements, in contrast to the characteristic high-low-high trend of adjacent group
      III (In) and group IV (Sn) elements. Additionally, these data complement those of
      previous studies of metal-organic species and provide a foundation of
      thermochemical data that can aid in the selection of CVD precursors and
      deposition conditions for the growth of antimony-containing materials.

PMID- 16640391
TI  - Computational studies on polynitrohexaazaadmantanes as potential high energy
      density materials.
AB  - Polynitrohexaazaadamantanes (PNHAAs) have been the subject of much recent
      research because of their potential as high energy density materials (HEDMs). The
      B3LYP/6-31G method was employed to evaluate the heats of formation (HOFs) for
      PNHAAs by designing isodesmic reactions. The HOFs are found to be correlative
      with the number (n) and the space orientations of nitro groups. Detonation
      velocities (D) and detonation pressures (P) were estimated for PNHAAs by using
      the well-known Kamlet-Jacobs equations, based on the theoretical densities (rho)
      and HOFs. It is found that D and P increase as n ranges from 1 to 6, and PNHAAs
      with 4-6 nitro groups meet the criteria of an HEDM. When n is over 6, rho of
      PNHAAs slightly increases; however, the chemical energy of detonation (Q)
      decreases so greatly that both D and P decrease. The calculations on bond
      dissociation energies suggest that the N-N bond be the trigger bond during the
      pyrolysis initiation process of each PNHAA, and with increasing n, N-N bond
      dissociation energy (E(N-N)) decreases on the whole, that is to say, the relative
      stability of PNHAAs decreases. All E(N-N)(s) of PNHAAs are more than 30 kcal.mol(
      1), which further proves that four PNHAAs with 4-6 nitro groups can be used as
      the candidates of HEDMs. Considering the synthesis difficulty and the performance
      as an energetic compound, we finally recommended 2,4,6,8,10
      pentanitrohexaazaadamantane as the target HEDM for PNHAAs.

PMID- 16640392
TI  - On the electron donor and the electrophilic substitution activating abilities of
      substituents in uracil.
AB  - QTAIM properties for uracil and 18 derivatives containing the substituents 
      NH(2), -OH, -OCH(3), -SH, -F, -Cl, -CH(3) -NO(2), and -Li in position 5 or 6 were
      computed on MP2/6-31++G//MP2/6-31G charge densities. The results indicate that 
      OH, -OCH(3), and -NH(2) groups are really retrieving charge from the ring. Also,
      the activating ability of the substituent groups, usually considered as the
      variation of electron population at the carbon where the electrophilic attack
      takes place, C, was studied. The study shows that the activating ability is
      reflected by the variation of pi charge or quadrupole moment at C, and also by
      the variation of the Laplacian of the charge density in the secondary charge
      concentration points around C (SCC-C). They indicate a similar, but not exactly
      equal, graduation of activating ability. The relative behavior of the
      substituents is basically the same as in benzene, though benzene has more
      tendency to concentrate charge in the SCC-C regions than uracil, where this
      tendency is larger for 6- than for 5-derivatives. sigma(+/-)(R) Taft parameters
      are found to display good correlations with the above indicated activating
      indexes. Finally, the resonance model predicts most of the main variations
      displayed by QTAIM atomic pi electron populations of derivatives with regard to
      uracil, but there are still some significant variations of the pi electron charge
      that it cannot predict.

PMID- 16640393
TI  - Quantification of intramolecular nonbonding interactions in organochalcogens.
AB  - Intramolecular nonbonding interactions between chalcogen atoms in a series of
      ortho substituted arylselenides (S/O...Se-Y, with Y = -Me, -CN, -Cl, and -F) are
      quantified using the coupled cluster CCSD(T)/cc-pVDZ level of theory. A
      homodesmic reaction method as well as an ortho-para approach are employed in
      evaluating the strength of intramolecular interactions. Comparison of the results
      obtained using the ab initio MP2 method and pure and hybrid density functional
      theories are performed with that of the coupled cluster values to assess the
      quality of different density functionals in evaluating the strength of nonbonding
      interactions. The interaction energies are found to be higher when the thioformyl
      group acts as the donor and the Se-F bond acts as the acceptor. In a given series
      with the same donor atom, the strength of the interaction follows the order Me <
      CN < Cl < F, exhibiting fairly high sensitivity to the group attached to selenium
      (Se-Y). Analysis of electron density at the S/O...Se bond critical point within
      the Atoms in Molecule framework shows a very good correlation with the computed
      intramolecular interaction energies.

PMID- 16640394
TI  - Stabilities and properties of complexes pairing hydroperoxyl radical with
      monohalomethanes.
AB  - UMP2/aug-cc-pvdz calculations are used to analyze the interaction between
      hydroperoxyl radical (HOO) and CH(3)X (X = F, Cl, Br). Two minima are located on
      the potential energy surface of each complex. The more strongly bound contains a
      OH...X bond, along with CH...O; only CH...O bonds occur in the less stable
      minimum. Binding energies of the dominant minimum lie in the range of 20-24
      kJ/mol, with X = F the most strongly bound. Analysis of the perturbations of the
      covalent bond lengths within each subunit caused by complexation, coupled with
      vibrational frequencies and charge transfers, opens a window into the nature of
      the interactions.

PMID- 16640395
TI  - Assessment of several hybrid DFT functionals for the evaluation of bond length
      alternation of increasingly long oligomers.
AB  - We have optimized the ground-state geometry of nine series of increasingly long
      oligomers, using six hybrid density functionals (O3LYP, B3LYP, B97-1, B98, PBE0,
      and BHHLYP) combined with three different atomic basis sets. In each case, the
      obtained bond length alternation (BLA) is compared to the corresponding MP2
      values. Three phenomenological categories have been set up. In the first, the BLA
      exponentially decreases, in which case all the tested functionals give results in
      very good agreement with MP2. In the second category fall the symmetric oligomers
      that, due to the Peierls theorem, show large BLA. For these chains, BHHLYP tends
      to give too large and quickly converging BLA wrt chain length, while O3LYP often
      leads to the opposite misjudgments, and the remaining hybrids provide valuable
      results. In the third category, one finds asymmetric compounds presenting
      significantly unequal bond lengths, for which the divergence between DFT and wave
      function approaches can be dramatic. Indeed, all hybrids yield too small BLA
      values, especially for long chain lengths. We also study the effect of chain
      conformation on the BLA.

PMID- 16640396
TI  - Structure and stability of salicylic acid-water complexes and the effect of
      molecular hydration on the spectral properties of salicylic acid.
AB  - Density functional theory with B3LYP parametrization and 6-311++G(d,p) basis set
      has been used to investigate the structure and stability of salicylic acid-water
      complexes. The vertical excitation energies for these complexes have been
      computed using time-dependent density functional theory (with B3LYP
      parametrization and a 6-311++G(d,p) basis set). It is shown that the hydrogen
      bond between the carboxylic hydrogen and the oxygen of water is the strongest
      among all possible hydrogen bonds in the system. The hydrogen bond strength in
      salicylic acid-water complexes seems to be nearly additive. The change in
      absorption maximum (lambda(max)) corresponding to the vertical excitation energy
      for the first three excited singlet and triplet states of the complex with 1-3
      water molecules is nominal (approximately 1-3 nm). But with the addition of the
      fourth water molecule, the lambda(max) for S(1) and T(1) decreases by
      approximately 17 nm and it increases for S(2) and S(3) by about the same amount.
      The decrease in lambda(max) for transition to the T(2) state on the addition of
      the fourth water molecule is only approximately 9 nm. There seems to be an
      intersystem crossing between the S(1) and T(3) states that could account for the
      observed fluorescence quenching of salicylic acid in water.

PMID- 16640400
TI  - Comparison of linear and 2D IR spectra in the presence of fast exchange.
AB  - The few picosecond time scale H-bond making and breaking in the system
      acetonitrile-methanol dominates the mechanism of vibrational coherence transfer
      that is evident in the shapes of both the linear and nonlinear IR spectra of the
      CN group.

PMID- 16640401
TI  - Functionalized single graphene sheets derived from splitting graphite oxide.
AB  - A process is described to produce single sheets of functionalized graphene
      through thermal exfoliation of graphite oxide. The process yields a wrinkled
      sheet structure resulting from reaction sites involved in oxidation and reduction
      processes. The topological features of single sheets, as measured by atomic force
      microscopy, closely match predictions of first-principles atomistic modeling.
      Although graphite oxide is an insulator, functionalized graphene produced by this
      method is electrically conducting.

PMID- 16640402
TI  - Comparison of new microemulsion prepared "Pt-in-Ceria" catalyst with conventional
      "Pt-on-Ceria" catalyst for water-gas shift reaction.
AB  - New "Pt-in-CeO(2)" catalyst prepared by microemulsion method is shown to give
      higher activity for a water-gas shift reaction but with no formation of CH(4),
      the side product from hydrogenation of carbon oxides using a hydrogen-rich
      reformate as compared to conventional "Pt-on-CeO(2)" catalysts. Detailed
      characterization by DRIFT analysis and temperature programmed reduction presented
      in this work clearly suggest the ceria coverage on Pt inhibits the metal from
      forming a strong CO adsorption.

PMID- 16640403
TI  - Calculation of activation energies for transport and recombination in mesoporous
      TiO2/dye/electrolyte films--taking into account surface charge shifts with
      temperature.
AB  - Transient photovoltage and photocurrent measurements have been employed to
      determine the recombination and transport kinetics in operating dye-sensitized
      photovoltaic cells as a function of potential and temperature. Photocurrent
      transients have been taken at the open circuit potential, as opposed to the
      standard measurement at short circuit. Kinetic results have been used to
      calculate the activation energy as function of the Fermi level position in the
      TiO(2). In the calculation of activation energies, we have explicitly taken into
      account the temperature dependence of the offset between the electrolyte redox
      potential and the conduction band edge. This new method gives activation energies
      that decrease linearly as the Fermi level position moves toward the conduction
      band edge, as expected, but not found in previous studies. The results are
      consistent with the presence of a distribution of traps below the TiO(2)
      conduction band, the detrapping from which limits both the transport and the
      recombination of electrons.

PMID- 16640404
TI  - SnO2 nanoparticle-functionalized boron nitride nanotubes.
AB  - Boron nitride nanotubes (BNNTs) were synthesized by a carbon-free chemical vapor
      deposition method using boron and metal oxide as reactants. Then SnO(2)
      nanoparticles were functionalized on them via a simple wet chemistry method.
      Detailed transmission electron microscopy (TEM) observations reveal that SnO(2)
      nanoparticles may cover the tube surface or be encapsulated in tube channels. The
      lattice distances of both BNNT and SnO(2) have been changed due to the strong
      interactions between them. The band gap energy of SnO(2) particles is found
      enlarged due to the size effect and interaction with BNNTs.

PMID- 16640405
TI  - n- and isoalkane adsorption mechanisms on zeolite MCM-22.
AB  - Low-coverage adsorption properties (Henry constants, adsorption enthalpy, and
      entropy) of linear and branched alkanes (C3-C8) on zeolite MCM-22 were determined
      using the chromatographic technique at temperatures between 420 and 540 K. It was
      found that adsorption enthalpy and entropy of linear alkanes vary in a
      nonmonotonic way with carbon number. The adsorption behavior of alkanes was
      rationalized on the basis of the pore geometry. Short molecules prefer to reside
      in the pockets of the MCM-22 supercage, where they maximize energetic interaction
      with the zeolite. Longer molecules reside in the larger central part of the
      supercage. For carbon numbers up to six, singly branched alkanes are selectively
      adsorbed over their linear counterparts. This preference originates from the
      entropic advantage of singly branched molecules inside MCM-22 supercages, where
      these species have high rotational freedom because of their small length.

PMID- 16640406
TI  - New preparation method of gold nanoparticles on SiO2.
AB  - It is shown that adsorption of the [Au(en)(2)](3+) cationic complex can be
      successfully employed for the deposition of gold nanoparticles (1.5 to 3 nm) onto
      SiO(2) with high metal loading, good dispersion, and small Au particle size. When
      the solution pH increases (from 3.8 to 10.5), the Au loading in the Au/SiO(2)
      samples increases proportionally (from 0.2 to 5.5 wt %), and the average gold
      particle size also increases (from 1.5 to 2.4 nm). These effects are explained by
      the increase in the amount of negatively charged sites present on the SiO(2)
      surface, namely, when the solution pH increases, a higher number of
      [Au(en)(2)](3+) species can be adsorbed. Extending the adsorption time from 2 to
      16 h gives rise to an increase in the gold loading from 3.3 to 4.0 wt % and in
      the average particle size from 1.8 to 2.9 nm. Different morphologies of gold
      nanoparticles are present as a function of the particle size. Particles with a
      size of 3-5 nm show defective structure, some of them having a multiple twinning
      particle (MTP) structure. At the same time, nanoparticles with an average size of
      ca. 2 nm exhibit defect-free structure with well-distinguishable {111} family
      planes. TEM and HAADF observations revealed that Au particles do not agglomerate
      on the SiO(2) support: gold is present on the surface of SiO(2) only as small
      particles. Density functional theory calculations were employed to study the
      mechanisms of [Au(en)(2)](3+) adsorption, where neutral and negatively charged
      silica surfaces were simulated by neutral cluster Si(4)O(10)H(4) and negatively
      charged cluster Si(4)O(10)H(3), respectively. The calculation results are totally
      consistent with the suggestion that the deposition of gold takes place according
      to a cationic adsorption mechanism.

PMID- 16640407
TI  - Growth mechanism, photoluminescence, and field-emission properties of ZnO
      nanoneedle arrays.
AB  - ZnO nanoneedle arrays have been grown on a large scale with a chemical vapor
      deposition method at 680 degrees C. Zn powder and O(2) gas are employed as source
      materials, and catalyst-free Si plates are used as substrates. Energy-dispersive
      X-ray and X-ray diffraction analyses show that the nanoneedles are almost pure
      ZnO and preferentially aligned in the c-axis direction of the wurtzite structure.
      The growth mechanism of ZnO nanoneedle arrays is discussed with the thermodynamic
      theory and concluded to be the result of the co-effect of the surface tension and
      diffusion. Photoluminescence spectrum of the as-grown products shows a strong
      emission band centering at about 484 nm, which originates from oxygen vacancies.
      Field-emission examination exhibits that the ZnO nanoneedle arrays have a turn-on
      voltage at about 5.3 V/microm.

PMID- 16640408
TI  - Effect of pore packing defects in 2-d ordered mesoporous carbons on ionic
      transport.
AB  - Ordered mesoporous materials show great importance in energy, environmental, and
      chemical engineering. The diffusion of guest species in mesoporous networks plays
      an important role in these applications, especially for energy storage, such as
      supercapacitors based on ordered mesoporous carbons (OMCs). The ion diffusion
      behavior in two different 2-D hexagonal OMCs was investigated by using cyclic
      voltametry and electrochemical impedance spectroscopy. In addition, transmission
      electron microscopy, small-angle X-ray diffraction, and nitrogen cryosorption
      methods were used to study the pore structure variations of these two OMCs. It
      was found that, for the OMC with defective pore channels (termed as pore packing
      defects), the gravimetric capacitance was greatly decayed when the voltage scan
      rate was increased. The experimental results suggest that, for the ion diffusion
      in 2-D hexagonal OMCs with similar mesopore size distribution, the pore packing
      defect is a dominant dynamic factor.

PMID- 16640409
TI  - Inclusion complexes of beta-cyclodextrin with ionic liquid surfactants.
AB  - The three kinds of ionic liquid (IL) surfactants, 1-dodecyl-3-methylimidazolium
      hexafluorophosphate (C(12)mimPF(6)), 1-tetradecyl-3-methylimidazolium
      hexafluorophosphate (C(14)mimPF(6)), and 1-hexadecyl-3-methylimidazolium
      hexafluorophosphate (C(16)mimPF(6)), were used to form the inclusion complexes
      (ICs) with beta-cyclodextrin (beta-CD). The surface tension measurements revealed
      that there were two kinds of inclusion formations, 1:1 and 1:2 (beta-CD/IL)
      stoichiometry for beta-CD-C(12)mimPF(6) and beta-CD-C(14)mimPF(6) ICs, and only
      1:1 stoichiometry for beta-CD-C(16)mimPF(6) ICs. These inclusion compounds were
      further characterized by XRD, (13)C CP/MAS NMR, (1)H NMR, rotating frame nuclear
      Overhauser effect spectroscopy (ROESY), and thermogravimetry (TGA). The results
      showed that these ICs were fine crystalline powder. The host-guest system
      presented a channel-type structure, and each glucose unit of beta-CD was in a
      similar environment. It was suggested that hydrophobicity played a crucial role
      in supporting the formation of ICs. The decomposition temperature of these ICs
      was lower than those of their precursors. Furthermore, the possible inclusion
      structures were also speculated. These inclusion behaviors are likely to be used
      to recover ILs in the process of their preparation.

PMID- 16640410
TI  - Rotational mobility of guest molecules in o-terphenyl below T(g).
AB  - An optical anisotropy decay technique for measuring probe rotational times in
      glassy materials is presented. Rotational times from 10(1.4) to 10(5) s have been
      obtained for a molecule of 1-naphthyl-azomethoxybenzene (NAMB) in o-terphenyl
      (OTP) over a temperature range from T(g) +3.5 to T(g) -16.5 K. The rotational
      diffusion follows the temperature dependence of Debye-Stokes-Einstein down to
      T(g) -4 K with an activation energy of 320 +/- 30 kJ/mol. Below T(g) -9 K, the
      temperature dependence of rotation mobility was found to be much weaker with an
      activation energy of 70 +/- 15 kJ/mol.

PMID- 16640411
TI  - New route to synthesize highly active nanocrystalline sulfated titania-silica:
      synergic effects between sulfate species and silica in enhancing the
      photocatalysis efficiency.
AB  - A simple and efficient approach has been set up for fabricating highly active
      sulfated titania-silica (SO(4)(2-)/TiO(2)-SiO(2)): Ti(SO(4))(2) was hydrolyzed in
      the presence of silica, making it possible to sulfate titania and form titania
      silica mixed oxide in one step. This study was focused on investigating the roles
      of sulfate species and silica in improving the physicochemical properties and
      photoactivity of SO(4)(2-)/TiO(2)-SiO(2) through comparison with sulfated titania
      (SO(4)(2-)/TiO(2)) and sulfate-free catalysts (TiO(2) and TiO(2)-SiO(2)). Various
      characterization methods, including X-ray diffraction (XRD), Fourier transform
      infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and
      surface photovoltage spectroscopy (SPS), were employed to test these materials.
      The results revealed that for SO(4)(2-)/TiO(2) and TiO(2)-SiO(2) the sole
      presence of either sulfate species or silica imposes negative effects on the
      photocatalysis behavior of titania, leading them to have negligible
      photoactivities. On the contrary, in the case of SO(4)(2-)/TiO(2)-SiO(2), sulfate
      species and silica were proved to act in a cooperative manner; therefore, the
      following enhanced structure and surface properties of SO(4)(2-)/TiO(2)-SiO(2)
      were obtained: (i) relatively well-crystallized and smaller-size (15.4 nm)
      anatase-phase titania was formed upon 500 degrees C calcination without forming
      rutile phase and (ii) the formation of active surface sulfate species promotes
      the separation of photoinduced electron-hole pairs and therefore accelerates the
      photocatalysis reaction. Therefore, its photoactivity is enhanced as a result of
      the favorable synergic effects between sulfate species and silica due to their
      simultaneous presence.

PMID- 16640412
TI  - Microwave-assisted one-step synthesis of polyacrylamide-metal (M = Ag, Pt, Cu)
      nanocomposites in ethylene glycol.
AB  - Polyacrylamide-metal (M = Pt, Ag, Cu) nanocomposites with metal nanoparticles
      homogeneously dispersed in the polymer matrix have been successfully prepared
      with the corresponding metal salt and acrylamide monomer in ethylene glycol by
      microwave heating. This method is based on the single-step simultaneous formation
      of metal nanoparticles and polymerization of the acrylamide monomer, leading to a
      homogeneous distribution of metal nanoparticles in the polyacrylamide matrix.
      Ethylene glycol acts as both a reducing reagent and a solvent, thus no additional
      reductant is needed. Another advantage is that no initiator for AM polymerization
      and no surfactant for stabilization of metal nanoparticles are necessary. The
      products were characterized by X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), Fourier transform infrared (FTIR), ultraviolet visible
      (UV-vis) absorption spectra, and thermogravimetric (TG) and differential scanning
      calorimetric analysis (DSC).

PMID- 16640413
TI  - Ferroelectricity of pyridinium perchlorate, a molecular level point of view.
AB  - The behavior of ferroelectric and thermodynamic parameters of pyridinium
      perchlorate (PyClO(4)) was simulated based on experimental NMR data and
      properties of the individual constituting ions. Dynamic (2)H NMR spectroscopy was
      used to investigate the order-disorder character of ferroelectricity in PyClO(4).
      Quadrupole echo and inversion recovery experiments were performed in the range
      from 140 to 300 K. The spectra can be simulated by a rotational jump motion of
      the pyridinium cations about their pseudo-C(6) axis. This confirms that the
      ferroelectricity of this compound below a first-order phase transition at 248 K
      is primarily due to the ordering of cations along a ferroelectric axis. In an
      intermediate phase between 248 and 233 K, the cation-anion sublattice
      displacement mechanism also gives a small positive contribution to
      ferroelectricity. In the family of the ferroelectric pyridinium salts, the
      paraelectric-ferroelectric phase transition temperature increases with the size
      and polarizability of the constituting anions, suggesting that the main
      interaction for ferroelectric ordering occurs via an indirect superexchange
      mechanism, whereas in compounds with small anions of low polarizability the
      direct dipole-dipole interaction dominates and leads to antiferroelectric order.

PMID- 16640414
TI  - Tuning supported catalyst reactivity with dendrimer-templated Pt-Cu
      nanoparticles.
AB  - The effects of particle composition on heterogeneous catalysis were studied using
      dendrimer-encapsulated nanoparticles (DENs) as precursors to supported Pt-Cu
      catalysts. Bimetallic Pt-Cu DENs with varying Pt/Cu ratios were prepared in an
      anaerobic aqueous solution and deposited onto a high-purity commercial alumina
      support. The dendrimer template was then thermally removed to yield supported
      nanoparticle catalysts, which were studied with toluene hydrogenation and CO
      oxidation catalysis as well as infrared spectroscopy of adsorbed CO.
      Incorporating Cu into Pt nanoparticles had opposite effects on the two test
      reactions. Cu acted as a mild promoter for CO oxidation catalysis, and the
      promoting effect was independent of the amount of Cu present. Conversely, Cu
      acted as a strong poison for toluene hydrogenation catalysis, and the normalized
      rate tracked inversely with Cu content. Infrared spectroscopy of the supported
      nanoparticles indicated that electronic effects (electron donation from Cu to Pt)
      were minimal for these materials. Consequently, the catalysis results are
      interpreted in terms of potential structural differences as a function of Cu
      incorporation and reaction conditions.

PMID- 16640415
TI  - Biomimetic assembly of polypeptide-stabilized CaCO(3) nanoparticles.
AB  - In this paper, we report a simple polypeptide-directed strategy for fabricating
      large spherical assembly of CaCO(3) nanoparticles. Stepwise growth and assembly
      of a large number of nanoparticles have been observed, from the formation of an
      amorphous liquidlike CaCO(3)-polypeptide precursor, to the crystallization and
      stabilization of polypeptide-capped nanoparticles, and eventually, the spherical
      assembly of nanoparticles. The "soft" poly(aspartate)-capping layer binding on a
      nanoparticle surface resulted in the unusual soft nature of nanoparticle
      assembly, providing a reservoir of primary nanoparticles with a moderate
      mobility, which is the basis of a new strategy for reconstructing nanoparticle
      assembly into complex nanoparticle architectures. Moreover, the findings of the
      secondary assembly of nanoparticle microspheres and the morphology transformation
      of nanoparticle assembly demonstrate a flexible and controllable pathway for
      manipulating the shapes and structures of nanoparticle assembly. In addition, the
      combination of the polypeptide with a double hydrophilic block copolymer (DHBC)
      allows it to possibly further control the shape and complexity of the
      nanoparticle assembly. A clear perspective is shown here that more complex
      nanoparticle materials could be created by using "soft" biological proteins or
      peptides as a mediating template at the organic-inorganic interface.

PMID- 16640416
TI  - Eccentric phenomena at liquid mercury electrode/solution interfaces: upward,
      downward, and circular motions.
AB  - The present paper describes a visualization of unidirectional and circular
      motions triggered by an electrochemical redox reaction at a charged, bent, and
      streamed liquid electrode/liquid solution interface. The novel circular motion
      that induces a conversion of electrochemical energy into mechanical energy could
      be visualized for the first time at a hanging mercury drop electrode
      (HMDE)/dimethyl sulfoxide (DMSO) solution interface via the electrochromic
      reaction of 2,1,3-benzothiadiazole (BTD) by using a CCD-color video camera. The
      observed motions are self-insisting in nature and are tunable into upward,
      downward, clockwise, and anticlockwise ones by an appropriate choice of the
      experimental conditions. This circular motion is visualized for the first time as
      the cause of the well-known cyclic voltammetric anodic current oscillation at the
      HMDE. Several small perturbations, for example, surface tension, surface motion,
      bulk motion, diffusional mass transport, and surface electrochemical potential
      are considered to be endlessly amplified by their coupling in a cyclic chain,
      resulting in such macroscopic motions at the electrode/solution interface. All of
      the phenomena can be explained on the basis of the modern theory proposed by
      Aogaki et al. for the polarographic streaming maxima of the first kind.

PMID- 16640417
TI  - X-ray absorption spectroscopy of Mn/Co/TiO2 Fischer-Tropsch catalysts:
      relationships between preparation method, molecular structure, and catalyst
      performance.
AB  - The effects of the addition of manganese to a series of TiO(2)-supported cobalt
      Fischer-Tropsch (FT) catalysts prepared by different methods were studied by a
      combination of X-ray diffraction (XRD), temperature-programmed reduction (TPR),
      transmission electron microscopy (TEM), and in situ X-ray absorption fine
      structure (XAFS) spectroscopy at the Co and Mn K-edges. After calcination, the
      catalysts were generally composed of large Co(3)O(4) clusters in the range 15-35
      nm and a MnO(2)-type phase, which existed either dispersed on the TiO(2) surface
      or covering the Co(3)O(4) particles. Manganese was also found to coexist with the
      Co(3)O(4) in the form of Co(3-x)Mn(x)O(4) solutions, as revealed by XRD and XAFS.
      Characterization of the catalysts after H(2) reduction at 350 degrees C by XAFS
      and TEM showed mostly the formation of very small Co(0) particles (around 2-6
      nm), indicating that the cobalt phase tends to redisperse during the reduction
      process from Co(3)O(4) to Co(0). The presence of manganese was found to hamper
      the cobalt reducibility, with this effect being more severe when Co(3-x)Mn(x)O(4)
      solutions were initially present in the catalyst precursors. Moreover, the
      presence of manganese generally led to the formation of larger cobalt
      agglomerates ( approximately 8-15 nm) upon reduction, probably as a consequence
      of the decrease in cobalt reducibility. The XAFS results revealed that all
      reduced catalysts contained manganese entirely in a Mn(2+) state, and two well
      distinguished compounds could be identified: (1) a highly dispersed Ti(2)MnO(4)
      type phase located at the TiO(2) surface and (2) a less dispersed MnO phase being
      in the proximity of the cobalt particles. Furthermore, the MnO was also found to
      exist partially mixed with a CoO phase in the form of rock-salt Mn(1-x)Co(x)O
      type solid solutions. The existence of the later solutions was further confirmed
      by scanning transmission electron microscopy with electron energy loss
      spectroscopy (STEM-EELS) for a Mn-rich sample. Finally, the cobalt active site
      composition in the catalysts after reduction at 300 and 350 degrees C was linked
      to the catalytic performances obtained under reaction conditions of 220 degrees
      C, 1 bar, and H(2)/CO = 2. The catalysts with larger Co(0) particles (
      approximately >5 nm) and lower Co reduction extents displayed a higher intrinsic
      hydrogenation activity and a longer catalyst lifetime. Interestingly, the MnO and
      Mn(1-x)Co(x)O species effectively promoted these larger Co(0) particles by
      increasing the C(5+) selectivity and decreasing the CH(4) production, while they
      did not significantly influence the selectivity of the catalysts containing very
      small Co(0) particles.

PMID- 16640418
TI  - Acetic acid-water interaction in solid interfaces.
AB  - The adsorption of acetic acid on a proton-ordered water ice surface is modeled
      using periodic plane-waves density-functional theory. The structures of acetic
      acid adsorbed as a monomer or oligomers, hydrated or not, are calculated through
      gradient optimization. The resulting quantum electronic density of states are
      compared to metastable impact electron spectroscopy (MIES) results and lead to
      selection of the most plausible structures of acetic acid on water ice.
      Hypotheses are formulated for the structure of the acid film growing on the ice
      surface including mainly cyclic dimers and hydrated forms. Adsorptions of single
      water molecules on acetic acid crystal surfaces are also studied after
      optimization of the acetic acid crystal bulk and surface structure. More
      comparisons with spectroscopic studies are proposed in the accompanying paper.

PMID- 16640419
TI  - Interaction of acetic acid with solid water.
AB  - The interaction of acetic acid (AA, CH(3)COOH), with solid water, deposited on
      metals, tungsten and gold, at 80 K, was investigated. We have prepared acid/water
      interfaces at 80 K, namely, acid layers on thin films of solid water and H(2)O
      adlayers on thin acid films; they were annealed between 80 and 200 K. Metastable
      impact electron spectroscopy (MIES) and ultraviolet photoelectron spectroscopy
      UPS(HeII) were utilized to obtain information on the electronic structure of the
      outermost surface from the study of the electron emission from the weakest bound
      MOs of the acids, and of the molecular water. Temperature-programmed desorption
      (TPD) provided information on the desorption kinetics, and Fourier-transformed
      infrared spectroscopy (FTIR) provided information on the identification of the
      adsorbed species as well as on the water and acid crystallization. The results
      are compatible with the finding of ref 1 (preceding paper), made on the basis of
      DFT calculations, that AA adsorbs on ice as cyclic dimers. Above 120 K, a
      rearrangement of the AA dimers is suggested by a sharpening of the spectral
      features in the IR spectra and by spectral changes in MIES and UPS; this is
      attributed to the glass transition in AA around 130 K. Above 150 K the spectra
      transform into those characteristic for polycrystalline polymer chains. This
      structure is stable up to about 180 K; desorption of water takes place from
      underneath the AA film, and practically all water has desorbed through the AA
      film before AA desorption starts. There is no indication of water-induced
      deprotonation of the acid molecules. For the interaction of H(2)O molecules
      adsorbed on amorphous AA films, the comparison of MIES with the DFT results of
      ref 1 shows that the initial phase of exposure does not lead to the formation of
      a top-adsorbed closed water film at 80 K. Rather, the H(2)O molecules become
      attached to or incorporated into the preexisting AA network by H bonding; no
      water network is formed in the initial stage of the water adsorption. Also under
      these conditions no deprotonation of the acid can be detected.

PMID- 16640420
TI  - In situ surface oxidation study of a planar Co/SiO2/Si(100) model catalyst with
      nanosized cobalt crystallites under model Fischer-Tropsch synthesis conditions.
AB  - The oxidation of nanosized metallic cobalt to cobalt oxide during Fischer-Tropsch
      synthesis (FTS) has long been postulated as a major deactivation mechanism. In
      this study a planar Co/SiO(2)/Si(100) model catalyst with well-defined cobalt
      crystallites, close to the threshold value reported for oxidation in the
      literature (4-10 nm), was prepared by the spin coating method. The planar
      Co/SiO(2)/Si(100) model catalyst was characterized with atomic force microscopy,
      X-ray photoelectron spectroscopy, and Rutherford backscattering. The surface
      oxidation behavior of the nanosized metallic cobalt crystallites of 4-5 nm was
      studied using in situ near-edge X-ray absorption fine structure under model FTS
      conditions, i.e., H(2)/H(2)O = 1, P(Total) = 0.4 mbar, and 150-450 degrees C. No
      surface oxidation of metallic cobalt was observed under these model FTS
      conditions over a wide temperature range, i.e., 150-400 degrees C.

PMID- 16640421
TI  - Electron paramagnetic resonance and scanning tunneling microscopy investigations
      on the formation of F(+) and F(0) Color centers on the surface of thin MgO(001)
      films.
AB  - The formation of surface color centers (F(S) centers) by electron bombardment of
      thin MgO(001) films is investigated using electron paramagnetic resonance and low
      temperature scanning tunneling microscopy. At low electron doses both techniques
      indicate the formation of singly occupied color centers (F(S)(+)), whereas at
      high electron doses the doubly occupied type (F(S)(0)) is dominant. It is
      suggested that with increasing electron dose F(S)(+) centers are transformed into
      F(S)(0). Tunneling spectra of individual F(S)(0) centers reveal a large
      distribution of energetic positions of occupied and unoccupied states, which is
      caused by local variations of the coordination number of the defects and explains
      the broad signals usually detected with integrating spectroscopic techniques.

PMID- 16640422
TI  - Pore size or geometry: which determines the shape and inverse-shape selective
      adsorption of alkane isomers?
AB  - The adsorption of pure pentane (C(5)) isomers and their ternary mixture is
      simulated in a series of carbon nanoslits. With decreasing nanoslit pore size,
      shape selective adsorption first occurs in the order of nC(5) > or = iC(5) >
      neoC(5) due to the configurational entropy effect, then inverse-shape selective
      adsorption occurs in the order of nC(5) < iC(5) < or = neoC(5) due to the area
      entropy effect, and finally no adsorption occurs. The entropy effects lead to a
      large adsorptive separation among the C(5) isomers from their mixture. Similar
      behavior has been observed from the simulation of C(5) adsorption in carbon
      nanotubes with variation in pore size. These results reveal that pore size rather
      than geometry determines the shape and inverse-shape selective adsorption of
      alkane isomers in nanopores.

PMID- 16640423
TI  - 2D-mapping of the catalyst structure inside a catalytic microreactor at work:
      partial oxidation of methane over Rh/Al2O3.
AB  - Tremendous changes of the structure of Rh particles occurred during partial
      methane oxidation to hydrogen and carbon monoxide over a 2.5 wt % Rh/Al(2)O(3)
      catalyst upon ignition of the catalytic reaction. Furthermore, near the ignition
      temperature a variation in the Rh-valence state along the catalyst bed was
      observed. By combining hard X-ray absorption spectroscopy (X-ray absorption near
      edge structure, XANES) with a charged coupled device (CCD) camera and using a
      suitable spectroscopic cell with gas supply and on-line mass spectrometry, we
      demonstrate that 2D-mapping of the Rh-oxidation state in a catalyst bed can be
      achieved during the catalytic reaction. For this purpose, X-ray images were
      recorded with the CCD camera at each energy around the Rh K-edge with and without
      the spectroscopic cell. This resulted effectively in the transmitted and incident
      intensity at each energy and at each pixel of the spectroscopic cell.
      Reconstruction of the full Rh K-edge XANES spectra at each pixel revealed the
      local distribution of oxidized and metallic Rh-species in the catalyst bed. Along
      the catalyst bed, structural changes were found with a steep gradient within less
      than 100 microm. Furthermore, a characteristic cone toward the inlet of the
      spectroscopic cell was observed.

PMID- 16640424
TI  - Surface area and microporosity of carbon aerogels from gas adsorption and small-
      and wide-angle X-ray scattering measurements.
AB  - A carbon aerogel was obtained by carbonization of an organic aerogel prepared by
      sol-gel polymerization of resorcinol and formaldehyde in water. The carbon
      aerogel was then CO(2) activated at 800 degrees C to increase its surface area
      and widen its microporosity. Evolution of these parameters was followed by gas
      adsorption and small- and wide-angle X-ray scattering (SAXS and WAXS,
      respectively) with contrast variation by using dry and wet (immersion in benzene
      and m-xylene) samples. For the original carbon aerogel, the surface area,
      S(SAXS), obtained by SAXS, is larger than that obtained by gas adsorption
      (S(ads)). The values become nearly the same as the degree of activation of the
      carbon aerogel increases. This feature is due to the widening of the narrow
      microporosity in the carbon aerogel as the degree of activation is increased. In
      addition, WAXS results show that the short-range spatial correlations into the
      assemblies of hydrocarbon molecules confined inside the micropores are different
      from those existing in the liquid phase.

PMID- 16640425
TI  - In situ transient FTIR and XANES studies of the evolution of surface species in
      CO oxidation on Au/TiO2.
AB  - The adsorption of CO and its reaction with oxygen were investigated using a
      combination of in situ Fourier transform infrared spectroscopy, step response
      measurements in a microreactor, (18)O isotopic labeling, and X-ray absorption
      near edge structure spectroscopy. An as-prepared sample in which Au is present as
      a surface oxyhydroxy complex does not adsorb CO. On an activated sample in which
      only metallic Au is detected, 0.18 +/- 0.03 mol CO/(mol Au) are adsorbed on Au at
      -60 degrees C, which shows an IR band at 2090 cm(-1). When oxygen is present in
      the gas phase, this species reacts with a turnover rate of 1.4 +/- 0.2 mol CO(mol
      Au min)(-1), which is close to the steady-state turnover rate. In contrast, there
      is a very small quantity of adsorbed oxygen on Au. A small IR peak at 1242 cm(-1)
      appears when an activated sample is exposed to CO. It reacts rapidly with oxygen
      and is shifted to 1236 cm(-1) if (18)O is used. It is assigned to the possible
      intermediate hydroxycarbonyl.

PMID- 16640426
TI  - Investigation of solid surfaces modified by Langmuir-Blodgett monolayers using
      sum-frequency vibrational spectroscopy and X-ray photoelectron spectroscopy.
AB  - Langmuir-Blodgett (LB) monomolecular layers of alkylhydroxamic acids and
      alkylphosphonic acids on copper and iron substrates have been studied by X-ray
      photoelectron spectroscopy (XPS) and sum-frequency vibrational spectroscopy.
      According to the XPS results, the structures of the hydroxamic acid and
      phosphonic acid Langmuir-Blodgett films are very similar: the thickness of the
      layer of the hydrocarbon tails is typically 1.9-2.1 nm, while the layer of
      headgroups is about 0.3-0.35 nm thick. The tilt angle of the carbon chains is
      estimated to be 20-30 degrees with respect to the sample surface normal, and the
      molecules are connected to the substrate via their headgroups. Analysis of the P
      2p and N 1s lines indicates the presence of deprotonated headgroups. The
      substrate Cu 2p line includes a component which can be assigned to Cu(2+) ions in
      a thin Cu(OH)(2) layer. The deposition of LB layers led to significant decrease
      of the hydroxide-related signal, which indicates that binding of the headgroups
      to the surface is accompanied by the elimination of water molecules. The sum
      frequency spectra also clearly indicate that well-ordered monolayers can be
      formed by the Langmuir-Blodgett technique. Since the non-resonant background from
      the metal substrates renders the analysis of the spectra more difficult, model
      system samples on glass were prepared. It was found that the alkyl chains of the
      adsorbed acids predominantly adopt the all-trans conformation and form an ordered
      structure. Upper limits for the mean tilt angle of the terminal methyl groups are
      approximately 10-20 degrees.

PMID- 16640427
TI  - Electrochemical formation of a Pt/Zn alloy and its use as a catalyst for oxygen
      reduction reaction in fuel cells.
AB  - The characterization of an electrochemically created Pt/Zn alloy by Auger
      electron spectroscopy is presented indicating the formation of the alloy, the
      oxidation of the alloy, and the room temperature diffusion of the Zn into the Pt
      regions. The Pt/Zn alloy is stable up to 1.2 V/RHE and can only be removed with
      the oxidation of the base Pt metal either electrochemically or in aqua regia. The
      Pt/Zn alloy was tested for its effectiveness toward oxygen reduction. Kinetics of
      the oxygen reduction reaction (ORR) were measured using a rotating disk electrode
      (RDE), and a 30 mV anodic shift in the potential of ORR was found when comparing
      the Pt/Zn alloy to Pt. The Tafel slope was slightly smaller than that measured
      for the pure Pt electrode. A simple procedure for electrochemically modifying a
      Pt-containing gas diffusion electrode (GDE) with Zn was developed. The Zn-treated
      GDE was pressed with an untreated GDE anode, and the created membrane electrode
      assembly was tested. Fuel cell testing under two operating conditions (similar
      anode and cathode inlet pressures, and a larger cathode inlet pressure) indicated
      that the 30 mV shift observed on the RDE was also evident in the fuel cell tests.
      The high stability of the Pt/Zn alloy in acidic environments has a potential
      benefit for fuel cell applications.

PMID- 16640428
TI  - Characterization of the adsorption of Ru-bpy dyes on mesoporous TiO2 films with
      UV-Vis, Raman, and FTIR spectroscopies.
AB  - In the present work the adsorption of a new dye, [Ru(dcbpyH(2))(2)(bpy
      TPA(2))](PF(6))(2), and the well-known (Bu(4)N)(2)[Ru(dcbpyH)(2)(NCS)(2)] complex
      on mesoporous anatase films were investigated to clarify the role of the
      carboxylate groups in the anchoring process of the dyes on the semiconductor
      surface. For this purpose UV-vis, Raman, resonance Raman, and ATR-FTIR
      spectroscopies have been used. The results of the Raman experiments at different
      excitation wavelengths demonstrate that photoinduced charge-transfer processes
      take place efficiently between the adsorbate and the substrate. Moreover, this is
      the first time that the Raman spectrum of a Ru-bpy dye (in this case, the dye
      N719) adsorbed on TiO(2) has been obtained without the resonance condition, only
      by means of SERS enhancement. The coordination of both complexes on the TiO(2)
      paste films is proposed to occur via bidentate or bridging linkage.

PMID- 16640429
TI  - Metal-support interaction and redox behavior of Pt(1 wt %)/Ce0.6Zr0.4O2.
AB  - The catalyst Pt(1 wt %)/Ce(0.6)Zr(0.4)O(2) is studied by CO-temperature
      programmed reduction (CO-TPR), isothermal oxygen storage complete capacity
      (OSCC), X-ray absorption spectroscopy (XAS) at the Pt L(III) edge, and in situ X
      ray diffraction (in situ XRD), with the aim of elucidating the role of supported
      metal in CO oxidation by ceria-based three-way catalysts (TWC). The redox
      behavior of Pt(1 wt %)/Ce(0.6)Zr(0.4)O(2) is compared to that of bare ceria
      zirconia. OSCC of redox-aged Pt/ceria-zirconia is twice that of bare ceria
      zirconia, and the maximum of CO consumption occurs at a temperature about 300 K
      lower than redox-aged ceria-zirconia. XAS analysis allows one to evidence the
      formation of a platinum-cerium alloy in redox-aged samples and the stability of
      the metal particles toward oxidation and sintering during high-temperature
      treatments. Under CO flux at 773 K, bare ceria-zirconia shows a continuous drift
      of diffraction peaks toward smaller Bragg angles, due to a progressive increase
      of Ce(III) content. Under the same treatment, the structural rearrangement of Pt
      supported ceria-zirconia starts after an induction time and takes place with an
      abrupt change of the lattice constant. The experimental evidence points to the
      role of supported Pt in modifying the redox properties of ceria-zirconia with
      respect to the bare support. It is proposed that the much faster bulk reduction
      observed by in situ XRD for redox-aged Pt/ceria-zirconia can be attributed to an
      easier release of reacted CO(2), producing a more effective turnover of reactants
      at the catalyst surface.

PMID- 16640430
TI  - Effect of the anchoring group in Ru-bipyridyl sensitizers on the
      photoelectrochemical behavior of dye-sensitized TiO2 electrodes: carboxylate
      versus phosphonate linkages.
AB  - The effects of the number of anchoring groups (carboxylate vs phosphonate) in Ru
      bipyridyl complexes on their binding to TiO(2) surface and the
      photoelectrochemical performance of the sensitized TiO(2) electrodes were
      systematically investigated. Six derivatives of Ru-bipyridyl complexes having di
      , tetra-, or hexacarboxylate (C2, C4, and C6) and di-, tetra-, or hexaphosphonate
      (P2, P4, and P6) as the anchoring group were synthesized. The properties and
      efficiencies of C- and P-complexes as a sensitizer depended on the number of
      anchoring groups in very different ways. Although C4 exhibited the lowest visible
      light absorption, C4-TiO(2) electrode showed the best cell performance and
      stability among C-TiO(2) electrodes. However, P6, which has the highest visible
      light absorption, was more efficient than P2 and P4 as a sensitizer of TiO(2).
      The surface binding (strength and stability) of C-complexes on TiO(2) is highly
      influenced by the number of carboxylate groups and is the most decisive factor in
      controlling the sensitization efficiency. A phosphonate anchor, however, can
      provide a stronger chemical linkage to TiO(2) surface, and the overall
      sensitization performance was less influenced by the adsorption capability of P
      complexes. The apparent effect of the anchoring group number on the P-complex
      sensitization seems to be mainly related with the visible light absorption
      efficiency of each P-complex.

PMID- 16640431
TI  - Kinetics of hydrogen production upon reduction of aqueous TiO2 nanoparticles
      catalyzed by Pd(0), Pt(0), or Au(0) coatings and an unusual hydrogen abstraction;
      steady state and pulse radiolysis study.
AB  - Reduction of H(+) by TiO(2) electrons (e(TiO)(2)(-)) in aqueous colloidal
      solution takes place in the presence of surface metal catalysts. The catalytic
      reduction gives rise to adsorbed hydrogen atoms. In the presence of Pd(0) or
      Pt(0), material balance shows that most of the adsorbed H atoms combine to
      molecular hydrogen. When the TiO(2) nanoparticles are partially coated with Au(0)
      instead of Pd(0) or Pt(0), a higher than expected molecular hydrogen level is
      observed, attributed to a short chain reaction involving hydrogen abstraction
      from 2-propanol. This unusual hydrogen abstraction reaction has not been reported
      before. The mechanism and energy balance are discussed. The surface modification
      of TiO(2) nanoparticles was carried out by reduction of K(2)PdCl(4), H(2)PtCl(6),
      or HAuCl(4) with e(TiO)(2)(-). The latter had been generated through electron
      injection from hydrated electrons, hydrogen atoms, or 2-propanol radicals,
      produced by gamma or pulse radiolysis prior to the addition of the metal
      compounds. Upon addition of the metal compounds, immediate reactions take place
      producing metals clusters (M(0)) by multistep reductions reactions on the TiO(2)
      surface. The chemical kinetics involving the different metals and the reaction
      rate constant of e(aq)(-) and e(TiO)(2)(-) with AuCl(4)(-) is also reported.

PMID- 16640432
TI  - Confinement-induced symmetry breaking of interfacial surfactant layers.
AB  - Interaction forces between mesoscopic objects are fundamental to soft-condensed
      matter and are among the prime targets of investigation in colloidal systems.
      Surfactant molecules are often used to tailor these interactions. The forces are
      experimentally accessible and for a first theoretical analysis one can make use
      of a parallel-plate geometry. We present molecularly realistic self-consistent
      field calculations for an aqueous nonionic surfactant solution near the critical
      micellization concentration, in contact with two hydrophobic surfaces. The
      surfactants adsorb cooperatively, and form a monolayer onto each surface. At weak
      overlap the force increases with increasing compression of the monolayers until
      suddenly a symmetry braking takes place. One of the monolayers is removed jump
      like and as the remaining monolayer can relax, some attraction is observed, which
      gives way to repulsion at further confinement. The restoring of symmetry at
      strong confinement occurs as a second-order transition and the force jumps once
      again from repulsion to attraction. It is anticipated that the metastable branch
      of the interaction curve will be probed in a typical force experiment. Under
      normal conditions pronounced hysteresis in the surface force is predicted,
      without the need to change the adsorbed amount jump-like.

PMID- 16640433
TI  - First-principles calculations of AlN nanowires and nanotubes: atomic structures,
      energetics, and surface states.
AB  - We explore the atomic and electronic structures of single-crystalline aluminum
      nitride nanowires (AlNNWs) and thick-walled aluminum nitride nanotubes (AlNNTs)
      with the diameters ranging from 0.7 to 2.2 nm by using first-principles
      calculations and molecular dynamics simulations based on density functional
      theory (DFT). We find that the preferable lateral facets of AlNNWs and thick
      walled AlNNTs are {1010} surfaces, giving rise to hexagonal cross sections. Quite
      different from the cylindrical network of hexagons revealed in single-walled
      AlNNTs, the wall of thick-walled AlNNTs displays a wurtzite structure. The strain
      energies per atom in AlNNWs are proportional to the inverse of the wire diameter,
      whereas those in thick-walled AlNNTs are independent of tube diameter but
      proportional to the inverse of the wall thickness. Thick-walled AlNNTs are
      energetically comparable to AlNNWs of similar diameter, and both of them are
      energetically more favorable than single-walled AlNNTs. Both AlNNWs and AlNNTs
      are wide band gap semiconductors accompanied with surface states located in the
      band gap of bulk wurtzite AlN.

PMID- 16640434
TI  - Identification of destabilized metal hydrides for hydrogen storage using first
      principles calculations.
AB  - Hydrides of period 2 and 3 elements are promising candidates for hydrogen storage
      but typically have heats of reaction that are too high to be of use for fuel cell
      vehicles. Recent experimental work has focused on destabilizing metal hydrides
      through alloying with other elements. A very large number of possible
      destabilized metal hydride reaction schemes exist. The thermodynamic data
      required to assess the enthalpies of these reactions, however, are not available
      in many cases. We have used first principles density functional theory
      calculations to predict the reaction enthalpies for more than 100 destabilization
      reactions that have not previously been reported. Many of these reactions are
      predicted not be useful for reversible hydrogen storage, having calculated
      reaction enthalpies that are either too high or too low. More importantly, our
      calculations identify five promising reaction schemes that merit experimental
      study: 3LiNH(2) + 2LiH + Si --> Li(5)N(3)Si + 4H(2), 4LiBH(4) + MgH(2) --> 4LiH +
      MgB(4) + 7H(2), 7LiBH(4) + MgH(2) --> 7LiH + MgB(7) + 11.5H(2), CaH(2) + 6LiBH(4)
      --> CaB(6) + 6LiH + 10H(2), and LiNH(2) + MgH(2) --> LiMgN + 2H(2).

PMID- 16640435
TI  - Raman scattering studies on n-heptane under high pressure.
AB  - High-pressure Raman scattering studies at ambient temperature are performed on n
      heptane. We observe a liquid-solid transition around 1.5 GPa from the changes in
      the Raman spectra. This has been reported in earlier works. With increasing
      pressure, we observe large changes in the Raman modes and the spectra show a
      distinct change around 7.5 GPa. This marks the solid-solid transition at 7.5 GPa
      observed in n-heptane for the first time. As predicted in theoretical work, we
      observe dampening of methyl rotation in n-heptane below 7.5 GPa. With increase in
      pressure above 7.5 GPa we observe a definitive conversion of gauche to trans
      conformation in the solid phase. Upon release of pressure we do not observe any
      hysteresis, which suggests that the solid-solid transition takes place with no
      volume change or is a second-order transition. In this paper we propose this
      transition to be an orientational order-disorder transition driven by the
      dampening of the rotation of the methyl group.

PMID- 16640436
TI  - Monte Carlo simulations of the hydrophobic effect in aqueous electrolyte
      solutions.
AB  - The hydrophobic interaction between two methane molecules in salt-free and high
      salt-containing aqueous solutions and the structure in such solutions have been
      investigated using an atomistic model solved by Monte Carlo simulations.
      Monovalent salt representing NaCl and divalent salt with the same
      nonelectrostatic properties as the monovalent salt have been used to examine the
      influence of the valence of the salt species. In salt-free solution the effective
      interaction between the two methane molecules displayed a global minimum at close
      contact of the two methane molecules and a solvent-separated secondary minimum.
      In 3 and 5 M monovalent salt solution the potential of mean force became slightly
      more attractive, and in a 3 M divalent salt solution the attraction became
      considerably stronger. The structure of the aqueous solutions was determined by
      radial distribution functions and angular probability functions. The distortion
      of the native water structure increased with ion valence. The increase of the
      hydrophobic attraction was associated with (i) a breakdown of the tetrahedral
      structure formed by neighboring water molecules and of the hydrogen bonds between
      them and (i) the concomitant increase of the solution density.

PMID- 16640437
TI  - Molecular dynamics simulation of liquid sulfur dioxide.
AB  - A previously proposed model for molecular dynamics (MD) simulation of liquid
      sulfur dioxide, SO(2), has been reviewed. Thermodynamic, structural, and
      dynamical properties were calculated for a large range of thermodynamic states.
      Predicted (P,V,T) of simulated system agrees with an elaborated equation of state
      recently proposed for liquid SO(2). Calculated heat capacity, expansion
      coefficient, and isothermal compressibility are also in good agreement with
      experimental data. Calculated equilibrium structure agrees with X-ray and neutron
      scattering measurements on liquid SO(2). The model also predicts the same
      (SO(2))(2) dimer structure as previously determined by ab initio calculations.
      Detailed analysis of equilibrium structure of liquid SO(2) is provided,
      indicating that, despite the rather large dipole moment of the SO(2) molecule,
      the structure is mainly determined by the Lennard-Jones interactions. Both single
      particle and collective dynamics are investigated. Temperature dependency of
      dynamical properties is given. The MD results are compared with previous findings
      obtained from the analysis of inelastic neutron scattering spectra of liquid
      SO(2), including wave-vector dependent structural relaxation, tau(k), and
      viscosity, eta(k).

PMID- 16640438
TI  - Solvation structure and transport of acidic protons in ionic liquids: a first
      principles simulation study.
AB  - Ab initio simulations of a single molecule of HCl in liquid dimethyl imidazolium
      chloride [dmim][Cl] show that the acidic proton exists as a symmetric, linear
      ClHCl(-) species. Details of the solvation structure around this molecule are
      given. The proton-transfer process was investigated by applying a force along the
      antisymmetric stretch coordinate until the molecule broke. Changes in the free
      energy and local solvation structure during this process were investigated. In
      the reaction mechanism identified, a free chloride approaches the proton from the
      side. As the original ClHCl(-) distorts and the incoming chloride forms a new
      bond to the proton, one of the original chlorine atoms is expelled and a new
      linear molecule is formed.

PMID- 16640439
TI  - Molecular dynamics simulations of neutral chlorpromazine in zwitterionic
      phospholipid monolayers.
AB  - Molecular dynamics simulations have been performed to investigate the
      interactions between chlorpromazine (CPZ), a neuroleptic drug used in the
      treatment of psychiatric disorders, and dipalmitoylphosphatidylcholine (DPPC), a
      zwitterionic phospholipid, in Langmuir monolayers. The results from simulations
      carried out at different monolayer surface densities were able to capture
      important features of the CPZ-lipid interaction. We find that neutral
      (unprotonated) CPZ is preferentially located in the lipid tail region of the
      phospholipids, in little contact with the aqueous phase, and that the orientation
      of its rigid ring structure and tail conformation vary with lipid surface
      density. CPZ is found to promote ordering of the lipid tails for all surface
      densities because of a reduction in the effective surface area per lipid upon
      addition of the drug. Similar effects have been observed in previous studies of
      cholesterol in DPPC monolayers, in which lipid tails were seen to order around
      the solute. This feature, however, is quite distinct from what we observe for the
      most dense monolayer considered here (area per lipid of 50 A(2)), for which we
      find that CPZ promotes a local distortion of the lipid tails in its immediate
      vicinity and a concomitant ordering of lipid tails located further away from the
      solute. This view is further supported by the results obtained for an
      approximated nonlinear vibrational sum frequency generation susceptibility, which
      showed greater tail disorder close to CPZ.

PMID- 16640440
TI  - On the interaction of bare and hydrated aluminum ion with nucleic acid bases (U,
      T, C, A, G) and monophosphate nucleotides (UMP, dTMP, dCMP, dAMP, dGMP).
AB  - The B3LYP/6-311+G(2df,2p) density functional approach was used to study the
      interaction that aluminum trication, in the bare and hydrated forms, establishes
      with the nucleic acid bases and the corresponding monophosphate nucleotides. In
      this investigation, we determine equilibrium geometry of all possible complexes
      resulting from the attachment of the ion on the different binding sites selected
      on each ligand. The relative energies of complexes and metal ion affinities are
      also given. The most meaningful aspect was found to lie in the energetics of this
      interaction that underlines a very high affinity of aluminum ion for the examined
      biological systems.

PMID- 16640441
TI  - Spin labeling of Natronomonas pharaonis halorhodopsin: probing the cysteine
      residues environment.
AB  - Halorhodopsin from Natronomonas pharaonis (pHR) is a light-driven chloride pump
      that transports a chloride anion across the plasma membrane following light
      absorption by a retinal chromophore which initiates a photocycle. Analysis of the
      amino acid sequence of pHR reveals three cysteine residues (Cys160, Cys184, and
      Cys186) in helices D and E. Here we have labeled the cysteine residues with
      nitroxide spin labels and studied using electron paramagnetic resonance (EPR)
      spectroscopy their mobility, accessibility to various reagents, and the distance
      between the labels. It was revealed by following the d(1)/d parameter that the
      distance between the spin labels is ca. 13-15 Angstrom. The EPR spectrum suggests
      that one label has a restricted mobility while the other two are more mobile.
      Only one label is accessible to hydrophilic paramagnetic broadening reagents
      leading to the conclusion that this label is exposed to the water phase. All
      three labels are reduced by ascorbic acid and reoxidized by molecular oxygen. The
      rate of the oxidation is accelerated following retinal irradiation indicating
      that the protein experiences conformation alterations in the vicinity of the
      labels during the pigment photocycle. It is suggested that Cys186 is exposed to
      the bulk medium while Cys184, located close to the retinal ionone ring, exhibits
      an immobilized EPR signal and is characterized by a hydrophobic environment.

PMID- 16640442
TI  - Monte Carlo and modified Tanford-Kirkwood results for macromolecular
      electrostatics calculations.
AB  - The understanding of electrostatic interactions is an essential aspect of the
      complex correlation between structure and function of biological macromolecules.
      It is also important in protein engineering and design. Theoretical studies of
      such interactions are predominantly done within the framework of Debye-Huckel
      theory. A classical example is the Tanford-Kirkwood (TK) model. Besides other
      limitations, this model assumes an infinitesimally small macromolecule
      concentration. By comparison to Monte Carlo (MC) simulations, it is shown that TK
      predictions for the shifts in ion binding constants upon addition of salt become
      less reliable even at moderately macromolecular concentrations. A simple
      modification based on colloidal literature is suggested to the TK scheme. The
      modified TK models suggested here satisfactorily predict MC and experimental
      shifts in the calcium binding constant as a function of protein concentration for
      the calbindin D(9k) mutant and calmodulin.

PMID- 16640443
TI  - Comparison of the intermolecular energy surfaces of amino acids: orientation
      dependent chiral discrimination.
AB  - In the present work, we compare the intermolecular energy surfaces of the alanine
      molecule in its neutral and zwitterionic state using ab initio theory (HF/6
      311++G) as a function of mutual orientation. Starting from the optimized
      structures of the nonbonded homochiral (l-l) and heterochiral (d-l) pairs of
      molecules, the energy surfaces are studied with rigid geometry by varying the
      distance and orientation. The potential energy surfaces of the l-l and d-l pairs
      are found to be dissimilar and reflect the underlying chirality of the homochiral
      pair and racemic nature of the heterochiral pair. The intermolecular energy
      surface of the l-l pair is more favorable than the corresponding energy surface
      of the d-l pair. The study, for the first time, reveals clear homochiral
      preference without use of parameters, which was unobserved in previous detailed
      simulations but predicted by theory. The electrostatic interaction further
      augments the chiral discrimination. The basis set superposition error (BSSE)
      corrected results show enhanced discrimination. Use of higher-level Moller
      Plesset perturbation theory (MP2) and further BSSE correction do not change the
      conclusions made at the Hartree-Fock (HF) level. The major conclusions based on
      HF and MP2 level calculations remain unaltered when the calculations of the
      potential energy surfaces for the neutral and zwitterionic pairs are repeated
      using the density functional theory (DFT) (B3LYP/6-311++G). The observed
      orientation dependence has significance in the biological chiral recognition as
      well as peptide synthesis at the peptidyl transferase center where the amino
      terminal and peptidyl terminal undergo mutual rotatory motion.

PMID- 16640444
TI  - Interaction of 4-nitroquinoline-1-oxide with indole derivatives and some related
      biomolecules: a study with magnetic field.
AB  - Laser flash photolysis and an external magnetic field have been used for the
      study of the interaction of 4-nitroquinoline-1-oxide (4NQO) with some indole
      derivatives, amino acids, tyrosine and tryptophan, and model proteins, lysozyme
      and bovine serum albumin. In an aprotic medium, photoinduced electron transfer
      (PET) from indoles to 4NQO is accompanied by proton transfer from the indole
      moieties irrespective of the substitution at the N-1 position. For 1,2
      dimethylindole, however, proton abstraction is hindered possibly due to steric
      effects. In a protic medium, obviously proton transfer is possible from the
      medium and is the dominating reaction following PET. The effect of an external
      magnetic field is very small for all the systems studied. This is attributed to a
      competition between geminate proton abstraction by the 4NQO radical anion from
      the partner radical cation and escape of the 4NQO radical anion to the medium
      followed by proton transfer. The latter process is more predominant, and the
      former one, which produces a small population of geminate spin-correlated radical
      pairs, leads to a minor field effect. Another interesting observation is the
      affinity of 4NQO toward the tryptophan residues in a protein environment. It is
      seen that PET takes place preferably from the tryptophan residues rather than
      from the tyrosine residues.

PMID- 16640445
TI  - Vibrational analysis of molecular interactions in aqueous glucose solutions.
      Temperature and concentration effects.
AB  - A vibrational analysis using FTIR and Raman spectroscopies was carried out on
      aqueous glucose solutions with a wide range of solute molar fractions and
      temperatures. The analysis was aimed at revealing structural changes in the local
      hydrogen-bonding (HB) network of liquid water, correlating these with the
      conservative properties of biomolecules, and comparing them with those of other
      sugars. The results of our measurements clearly show that the action of glucose
      is 2-fold; on one hand, there is a linkage with free hydroxyls of water; on the
      other, there is a slight lessening of the ordered (tetrahedral) H-bonded assembly
      of bulk H(2)O. These opposite effects do not balance each other, so the average
      HB interaction strength decreases on increasing glucose concentration. As a
      result, there is a reduction in the temperature dependence of solutions
      structure. In our opinion, this could be related to the low bioprotective action
      of this carbohydrate.

PMID- 16640446
TI  - Folding of ubiquitin: a simple model describes the strange kinetics.
AB  - The ubiquitin mutant UbG folding experiments of Sabelko et al., in which "strange
      kinetics" were observed, are interpreted in terms of a simple kinetic model. A
      minimal set of states consisting of a semicompact globule, two off-pathway traps,
      and the native state are included; the fully unfolded state is not considered
      because folding to the semicompact globule is fast. Both the low- and the high
      temperature experiments of Sabelko et al. are fitted by a system of kinetic
      equations determining the transitions between these states. It is possible that
      cold- and heat-denaturated states of UbG are the basis of the off-pathway traps.
      The fits of the kinetic model to the experimental results provides an estimate of
      the rate constants for the various reaction channels and show how their
      contributions vary with temperature. Introduction of an on-pathway intermediate
      instead of one of the off-pathway traps does not lead to agreement with the
      experiments.

PMID- 16640447
TI  - Similarity of salt influences on the pH of buffers, polyelectrolytes, and
      proteins.
AB  - Changes in pH induced by the addition of electrolytes to buffers,
      polyelectrolytes (a polycarboxy polymethylene and a polyethyleneimine), and
      proteins (casein, whey, and lysozyme) solutions are explored systematically. The
      two buffer systems are triethanolamine/triethanolammonium chloride and citric
      acid/sodium citrate. These are chosen because of the similarity of their acid
      base equilibria with those of amino acids predominant in most proteins, that is,
      amino acids that include carboxylate or ammonium groups in their structures. The
      pH of triethanolamine and of citrate buffers respectively increases and decreases
      when salt is added. At low electrolyte concentrations (<0.15 mol/kg), the
      phenomenon is well accounted for by standard electrostatic theories. pH values at
      higher salt concentrations are not reliable when measured with a commercial glass
      electrode without cross-checking by a standard hydrogen electrode. The changes of
      the pH values of polyelectrolyte and protein solutions with added salts turn out
      to be remarkably similar to the salt induced pH changes in the buffer solutions.
      It is even possible to qualitatively predict these changes in protein solutions
      simply from the primary protein structure. At least in the systems considered
      here, the specific ion effects on pH seem to correlate with the bulk activity
      coefficients of the added electrolytes, at least at moderate salt concentrations.

PMID- 16640448
TI  - Study on the supramolecular multirecognition mechanism of beta-naphthol/beta
      cyclodextrin/anionic surfactant in a tolnaftate hydrolysis system.
AB  - Based on the fact that tolnaftate degrade to beta-naphthol sodium (RONa) at 5.00
      mol/L NaOH solution and RO(-) was protonated to ROH after being acidified and
      adjusted to the pH 4.50 by acetic acid-sodium acetate buffer solution, we studied
      and discussed the mechanism of the supramolecular multirecognition interaction
      among the anionic surfactants sodium lauryl sulfate (SLS), beta-cyclodextrin
      (beta-CD), and beta-naphthol (ROH) by means of fluorescence spectrum, surface
      tension of the solution, infrared spectrograms, and (1)HNMR spectroscopy. The
      apparent formation constant of the ternary inclusion complex was determined to be
      (5.48 +/- 0.13) x 10(3) L(2)/mol(2). The thermodynamic parameters (DeltaG
      degrees, DeltaH degrees, DeltaS degrees ) for the formation of the inclusion
      complexes were obtained from the van't Hoff equation. It was indicated that the
      multiple and synergistic protection effect of SLS and beta-CD on the excited
      singlet state ROH played very important roles in the enhancement of the
      fluorescence of ROH. Results showed that, at room temperature, the naphthalene
      ring of ROH and the hydrophobic hydrocarbon chain of SLS were included into the
      cavity of beta-CD to form a ROH/SLS/beta-CD ternary inclusion complex with
      stoichiometry of 1:1:1, which provided effective protection for the excited state
      of ROH and increased the fluorescent intensity of ROH obviously.

PMID- 16640449
TI  - The role of water coordination in binary mixtures. A study of two model
      amphiphilic molecules in aqueous solutions by molecular dynamics and NMR.
AB  - Two binary aqueous mixtures which contain the small amphiphilic molecules TMAO
      (trimethylamine-N-oxide) and TBA (tert-butyl alcohol) have been investigated by
      molecular dynamics simulations and NMR chemical shift and self-diffusion
      measurements. TMAO is an osmolyte, while TBA is a monohydrate alcohol. Both
      possess bulky hydrophobic groups and polar heads, namely, NO in TMAO and OH in
      TBA. The hydrophilic/hydrophobic content of these isosteric molecules strongly
      modulates the structure and dynamics of the hydration shell, which is thought to
      be responsible for the effects observed on proteins and phospholipids. Simulation
      results, especially on hydrogen-bond networking, spatial correlations, and self
      diffusivity, are consistent with NMR data and agree well with previous numerical
      studies on similar solutions. The methods employed allow the elucidation of the
      microscopic features of the solutions. For TBA solutions, the hydration shell is
      found to have a low density and a large spatial spread, and thus, above the molar
      fraction of 0.03, reduction of hydrophobic hydration drives self-aggregation of
      the solute. This effect does not take place in TMAO solutions, where the
      hydration shell is more compact and stable, maintaining its structure over a
      wider range of solute concentrations.

PMID- 16640450
TI  - An analysis of electrical conductances of aqueous solutions of polybasic organic
      acids. Benzenehexacarboxylic (mellitic) acid and its neutral and acidic salts.
AB  - A general approach is proposed to analyze electrical conductivities in aqueous
      solutions of polybasic organic acids. Experimental conductivities are examined in
      the context of dissociation and hydrolysis reactions by applying the Quint
      Viallard conductivity equations and the Debye-Huckel equations for activity
      coefficients. The proposed numerical procedure is illustrated by the case of
      benzenehexacarboxylic (mellitic) acid and its neutral and acidic salts. From
      conductivity measurements of mellitic acid and its salts, performed in dilute
      aqueous solutions in the 278.15-308.15 K temperature range, the limiting
      conductances of mellitic anions, lambda(0)(1/jH(6-j)Mel(-j), T), j = 1, 2, 3, 4,
      5, 6 are determined.

PMID- 16640451
TI  - The influence of cardiovascular physiology on dose/pharmacokinetic and
      pharmacokinetic/pharmacodynamic relationships.
AB  - Inter- and intraindividual variability in the relationship between dose and
      clinical--or pharmacodynamic--response of a drug can be analysed in two steps:
      firstly, by considering the plasma pharmacokinetic response to a given dose and,
      secondly, by the connection between both pharmacokinetic and pharmacodynamic
      responses. As the cardiovascular system is the means of transport of endogenous
      and exogenous substances, blood flow fraction destined to each organ determines
      the relative mass of solute in plasma, which is constantly in contact with the
      tissue. Hence, not only the rate but also the extent of drug transfer would be
      increased when tissues are irrigated by a higher fraction of cardiac output.
      Aging and circadian rhythms present similar cardiac output distribution patterns
      when moving from young to aged adult and from nocturnal to diurnal hours. These
      two changes lead to an increased blood flow delivery to the extra-splanchnic
      renal region in the elderly and in the morning, but with a decreased cardiac
      output in aged individuals and an increased one during the day. This scenario
      allows us to forecast substance concentrations outside the blood vessels, which
      are responsible for the extent of drug elimination and the intensity of drug
      effect. So available data on disposition and pharmacodynamics of drugs might be
      explained from another point of view that challenges current knowledge.
      Furthermore, the administration of cardiovascular active drugs might reverse the
      chronological sequence between pharmacokinetic and pharmacodynamic responses,
      since they could modify blood flow distribution.

PMID- 16640452
TI  - Hypericum perforatum: a 'modern' herbal antidepressant: pharmacokinetics of
      active ingredients.
AB  - Hypericum perforatum (St John's Wort [SJW]) counts among the most favourite
      herbal drugs, and is the only herbal alternative to classic synthetic
      antidepressants in the therapy of mild to moderate depression. Several clinical
      studies have been conducted to verify the effectiveness of ethanolic or
      methanolic extracts of SJW. Alcoholic SJW extracts are a mixture of substances
      with widely varying physical and chemical properties and activities. Hyperforin,
      a phloroglucinol derivative, is the main source of pharmacological effects caused
      by the consumption of alcoholic extracts of SJW in the therapy of depression.
      However, several studies indicate that flavone derivatives, e.g. rutin, and also
      the naphthodianthrones hypericin and pseudohypericin, take part in the
      antidepressant efficacy. In contrast to the amount of documentation concerning
      clinical efficacy, oral bioavailability and pharmacokinetic data about the active
      components are rather scarce. The hyperforin plasma concentration in humans was
      investigated in a small number of studies. The results of these studies indicate
      a relevant plasma concentration, comparable with that used in in vitro tests.
      Furthermore, hyperforin is the only ingredient of H. perforatum that could be
      determined in the brain of rodents after oral administration of alcoholic
      extracts. The plasma concentrations of the hypericins were, compared with
      hyperforin, only one-tenth and, until now, the hypericins could not be found in
      the brain after oral administration of alcoholic H. perforatum extracts or pure
      hypericin. Until now, the pharmacokinetic profile of the flavonoids in humans
      after oral administration of an alcoholic H. perforatum extract has been
      investigated in only one study. More data are available for rutin and the
      aglycone quercetin after administration of pure substances or other flavonoid
      sources.

PMID- 16640453
TI  - Clinical pharmacokinetics of ranolazine.
AB  - Ranolazine is a compound that is approved by the US FDA for the treatment of
      chronic angina pectoris in combination with amlodipine, beta-adrenoceptor
      antagonists or nitrates, in patients who have not achieved an adequate response
      with other anti-anginals. The anti-anginal effect of ranolazine does not depend
      on changes in heart rate or blood pressure. It acts through different
      pharmacological mechanisms where inhibition of the late inward sodium current
      (reducing calcium overload and thereby left ventricular diastolic tension) is one
      plausible mechanism of reduced oxygen consumption. Initial studies used an oral
      solution or an immediate-release (IR) capsule, but subsequently an extended
      release (ER) formulation was developed to allow for twice-daily administration
      with maintained efficacy. Following administration of an oral solution or IR
      capsule, peak plasma concentrations (C(max)) are observed within 1 hour. After
      administration of radiolabelled ranolazine, 73% of the dose was excreted in
      urine, and unchanged ranolazine accounted for <5% of radioactivity in both urine
      and faeces. The absolute bioavailability ranges from 35% to 50%. Food has no
      effect on rate or extent of absorption from the ER formulation. Ranolazine
      protein binding is about 61-64% over the therapeutic concentration range. Volume
      of distribution at steady state ranges from 85 to 180 L. Ranolazine is
      extensively metabolised by cytochrome P450 (CYP) 3A enzymes and, to a lesser
      extent, by CYP2D6, with approximately 5% excreted renally unchanged. Elimination
      half-life of ranolazine is 1.4-1.9 hours but is apparently prolonged, on average,
      to 7 hours for the ER formulation as a result of extended absorption (flip-flop
      kinetics). Elimination occurs through parallel linear and saturable elimination
      pathways, where the saturable pathway is related to CYP2D6, which is partly
      inhibited by ranolazine. Oral plasma clearance diminishes with dose from, on
      average, 45 L/h at 500 mg twice daily to 33 L/h at 1000 mg twice daily. The
      departure from dose proportionality for this dose range is modest, with increases
      in steady-state C(max) and area under plasma concentration-time curve (AUC) from
      0 to 12 hours of 2.5- and 2.7-fold, respectively. Ranolazine pharmacokinetics are
      unaffected by sex, congestive heart failure and diabetes mellitus. AUC increases
      up to 2-fold with advancing degree of renal impairment. Ranolazine is a weak
      inhibitor of CYP3A, and increases AUC and C(max) for simvastatin, its metabolites
      and HMG-CoA reductase inhibitor activity <2-fold. Digoxin AUC is increased 40-60%
      by ranolazine through P-glycoprotein inhibition. Ranolazine AUC is increased by
      CYP3A inhibitors ranging from 1.5-fold for diltiazem 180 mg once daily to 3.9
      fold for ketoconazole 200 mg twice daily. Verapamil increases ranolazine exposure
      approximately 2-fold. CYP2D6 inhibition has a negligible effect on ranolazine
      exposure.

PMID- 16640454
TI  - Population pharmacokinetics of ceftriaxone and pharmacodynamic considerations in
      haemodialysed patients.
AB  - OBJECTIVES: To determine the pharmacokinetic parameters of ceftriaxone following
      an infusion in haemodialysed outpatients and to use these parameters for an
      optimisation of dosing based on pharmacodynamic indices. METHODS: Fifty
      haemodialysed patients were enrolled in a single-centre, prospective, open-label
      study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48
      hours for bronchopneumonia immediately after the dialysis session. Total plasma
      concentrations of ceftriaxone were analysed with a population pharmacokinetic
      approach using nonlinear mixed-effects modelling. Free drug concentrations were
      derived from published binding parameters in order to estimate the time when they
      exceed the minimum inhibitory concentration (MIC). RESULTS: The pharmacokinetics
      were best described by a two-compartment model. None of the covariates tested
      (age, bodyweight, height, sex, body mass index, albumin) influenced the
      pharmacokinetic parameters. The estimated population pharmacokinetic parameters
      (interindividual variability [percentage of coefficient of variation]) were
      clearance 0.36 L/h (48%), volume of distribution of the central compartment 4.53
      L (47%), intercompartmental clearance 10.8 L/h and volume of distribution of the
      peripheral compartment 9.54 L (63%). The terminal elimination half-life
      (t(1/2)beta) from plasma was 27.5 hours. The mean (range) times when the free
      drug concentration exceeded the MIC (T>MIC) following ceftriaxone 1 g infusion
      were 60.3 (53.0-67.7) hours and 2.5 (1.0-3.9) hours for the breakpoints 1 and 8
      mg/L (based on free drug concentration), respectively. After administration of
      ceftriaxone 2 g, the T>MIC was 88.5 (78.8-98.3) hours and 17.7 (13.3-22.0) hours
      for the breakpoints 1 and 8 mg/L, respectively. The simulated free drug
      concentrations (median, first and third quartile) for 48 and 72 hours following
      the first dose of ceftriaxone 1g were 1.11, 0.63 and 1.89 mg/L, and 0.63, 0.28
      and 1.18 mg/L, respectively. For ceftriaxone 2g infusion, the simulated free
      concentrations (median, first and third quartile) at 48 and 72 hours were 2.50,
      1.40 and 4.52 mg/L, and 1.37, 0.60 and 2.70 mg/L, respectively. CONCLUSIONS: On
      the basis of decreased clearance in haemodialysed patients, it can be argued that
      the dose of ceftriaxone should be decreased or the delay between doses should be
      increased. However, taking into account pharmacodynamic considerations, this
      study showed that following intravenous administration of ceftriaxone 1 g after
      each dialysis session, some patients were at risk of achieving a concentration
      below the MIC (1 mg/L), particularly if the second administration occurred 72
      hours after the first dosing. Thus, a dose of ceftriaxone 2 g intravenously is
      recommended immediately following dialysis, particularly in patients with severe
      infections or when the dosing interval will be higher than 48 hours.

PMID- 16640455
TI  - An extended terminal half-life for darbepoetin alfa: results from a single-dose
      pharmacokinetic study in patients with chronic kidney disease not receiving
      dialysis.
AB  - BACKGROUND AND OBJECTIVE: Anaemia is a major and persistent manifestation of
      chronic kidney disease (CKD) caused by the deficient production of erythropoietin
      in the kidneys, the prevalence of which is proportional to the deterioration in
      kidney function. Darbepoetin alfa, an erythropoiesis-stimulating protein,
      exhibits a lower clearance and longer terminal half-life in serum than
      recombinant human erythropoietin, thereby allowing for a reduced dosing
      frequency. A recent study in patients with CKD, using a 4-week sampling period,
      suggested that the terminal half-life of darbepoetin alfa in serum is longer than
      that reported in previous studies, which were based on a 1-week sampling period.
      This study was conducted to characterise the pharmacokinetic profile of a single
      subcutaneous dose of darbepoetin alfa 1 microg/kg in patients with CKD, using a
      sampling duration of 4 weeks, which was hypothesised to allow better
      characterisation of the terminal half-life in serum. METHODS: Twenty patients
      with CKD not on dialysis, with a calculated glomerular filtration rate of 20-60
      mL/min and who had not been treated with erythropoietic agents in the previous 12
      weeks, were enrolled into this single-dose, open-label study. Patients received a
      single subcutaneous dose of darbepoetin alfa (Aranesp) 1 microg/kg on day 1, and
      blood samples were collected for pharmacokinetic analyses predose, 6 and 12 hours
      postdose and up to 28 days postdose. Seroreactivity sampling and further safety
      laboratory tests (clinical chemistry and urinalysis) were also performed.
      Patients were assessed for adverse events at each study visit. The primary
      endpoint was characterisation of the terminal half-life following a single
      subcutaneous dose of darbepoetin alfa 1 microg/kg. RESULTS: The mean terminal
      half-life in serum of darbepoetin alfa was determined to be 69.6 hours. Peak
      serum concentrations were reached in a median time of 36 hours postdose, and a
      mean apparent clearance of 3.51 mL/h/kg was comparable to that observed
      previously in this patient population. CONCLUSION: Based on an extended sampling
      schedule of 4 weeks, the terminal half-life of darbepoetin alfa was approximately
      70 hours. This is longer than the 48.8 hours reported previously in patients with
      CKD on dialysis. These data suggest that the pharmacokinetic properties of
      darbepoetin alfa make this erythropoietic agent well suited to an extended dosing
      regimen.

PMID- 16640456
TI  - A novel strategy for physiologically based predictions of human pharmacokinetics.
AB  - BACKGROUND: The major aim of this study was to develop a strategy for predicting
      human pharmacokinetics using physiologically based pharmacokinetic (PBPK)
      modelling. This was compared with allometry (of plasma concentration-time
      profiles using the Dedrick approach), in order to determine the best approaches
      and strategies for the prediction of human pharmacokinetics. METHODS: PBPK and
      Dedrick predictions were made for 19 F. Hoffmann-La Roche compounds. A strategy
      for the prediction of human pharmacokinetics using PBPK modelling was proposed in
      this study. Predicted values (pharmacokinetic parameters, plasma concentrations)
      were compared with observed values obtained after intravenous and oral
      administration in order to assess the accuracy of the prediction methods.
      RESULTS: By following the proposed strategy for PBPK, a prediction would have
      been made prospectively for approximately 70% of the compounds. The prediction
      accuracy for these compounds in terms of the percentage of compounds with an
      average-fold error of <2-fold was 83%, 50%, 75%, 67%, 92% and 100% for apparent
      oral clearance (CL/F), apparent volume of distribution during terminal phase
      after oral administration (V(z)/F), terminal elimination half-life (t(1/2)), peak
      plasma concentration (C(max)), area under the plasma concentration-time curve
      (AUC) and time to reach C(max) (t(max)), respectively. For the other 30%
      compounds, unacceptable prediction accuracy was obtained in animals; therefore, a
      prospective prediction of human pharmacokinetics would not have been made using
      PBPK. For these compounds, prediction accuracy was also poor using the Dedrick
      approach. In the majority of cases, PBPK gave more accurate predictions of
      pharmacokinetic parameters and plasma concentration-time profiles than the
      Dedrick approach. CONCLUSIONS: Based on the dataset evaluated in this study, PBPK
      gave reasonable predictions of human pharmacokinetics using preclinical data and
      is the recommended approach in the majority of cases. In addition, PBPK modelling
      is a useful tool to gain insights into the properties of a compound. Thus, PBPK
      can guide experimental efforts to obtain the relevant information necessary to
      understand the compound's properties before entry into human, ultimately
      resulting in a higher level of prediction accuracy.

PMID- 16640457
TI  - Linking splicing to Pol II transcription stabilizes pre-mRNAs and influences
      splicing patterns.
AB  - RNA processing is carried out in close proximity to the site of transcription,
      suggesting a regulatory link between transcription and pre-mRNA splicing. Using
      an in vitro transcription/splicing assay, we demonstrate that an association of
      RNA polymerase II (Pol II) transcription and pre-mRNA splicing is required for
      efficient gene expression. Pol II-synthesized RNAs containing functional splice
      sites are protected from nuclear degradation, presumably because the local
      concentration of the splicing machinery is sufficiently high to ensure its
      association over interactions with nucleases. Furthermore, the process of
      transcription influences alternative splicing of newly synthesized pre-mRNAs.
      Because other RNA polymerases do not provide similar protection from nucleases,
      and their RNA products display altered splicing patterns, the link between
      transcription and RNA processing is RNA Pol II-specific. We propose that the
      connection between transcription by Pol II and pre-mRNA splicing guarantees an
      extended half-life and proper processing of nascent pre-mRNAs.

PMID- 16640458
TI  - Delaying the international spread of pandemic influenza.
AB  - BACKGROUND: The recent emergence of hypervirulent subtypes of avian influenza has
      underlined the potentially devastating effects of pandemic influenza. Were such a
      virus to acquire the ability to spread efficiently between humans, control would
      almost certainly be hampered by limited vaccine supplies unless global spread
      could be substantially delayed. Moreover, the large increases that have occurred
      in international air travel might be expected to lead to more rapid global
      dissemination than in previous pandemics. METHODS AND FINDINGS: To evaluate the
      potential of local control measures and travel restrictions to impede global
      dissemination, we developed stochastic models of the international spread of
      influenza based on extensions of coupled epidemic transmission models. These
      models have been shown to be capable of accurately forecasting local and global
      spread of epidemic and pandemic influenza. We show that under most scenarios
      restrictions on air travel are likely to be of surprisingly little value in
      delaying epidemics, unless almost all travel ceases very soon after epidemics are
      detected. CONCLUSIONS: Interventions to reduce local transmission of influenza
      are likely to be more effective at reducing the rate of global spread and less
      vulnerable to implementation delays than air travel restrictions. Nevertheless,
      under the most plausible scenarios, achievable delays are small compared with the
      time needed to accumulate substantial vaccine stocks.

PMID- 16640459
TI  - Whole-genome analysis of the SHORT-ROOT developmental pathway in Arabidopsis.
AB  - Stem cell function during organogenesis is a key issue in developmental biology.
      The transcription factor SHORT-ROOT (SHR) is a critical component in a
      developmental pathway regulating both the specification of the root stem cell
      niche and the differentiation potential of a subset of stem cells in the
      Arabidopsis root. To obtain a comprehensive view of the SHR pathway, we used a
      statistical method called meta-analysis to combine the results of several
      microarray experiments measuring the changes in global expression profiles after
      modulating SHR activity. Meta-analysis was first used to identify the direct
      targets of SHR by combining results from an inducible form of SHR driven by its
      endogenous promoter, ectopic expression, followed by cell sorting and comparisons
      of mutant to wild-type roots. Eight putative direct targets of SHR were
      identified, all with expression patterns encompassing subsets of the native SHR
      expression domain. Further evidence for direct regulation by SHR came from
      binding of SHR in vivo to the promoter regions of four of the eight putative
      targets. A new role for SHR in the vascular cylinder was predicted from the
      expression pattern of several direct targets and confirmed with independent
      markers. The meta-analysis approach was then used to perform a global survey of
      the SHR indirect targets. Our analysis suggests that the SHR pathway regulates
      root development not only through a large transcription regulatory network but
      also through hormonal pathways and signaling pathways using receptor-like
      kinases. Taken together, our results not only identify the first nodes in the SHR
      pathway and a new function for SHR in the development of the vascular tissue but
      also reveal the global architecture of this developmental pathway.

PMID- 16640460
TI  - A Src-like inactive conformation in the abl tyrosine kinase domain.
AB  - The improper activation of the Abl tyrosine kinase results in chronic myeloid
      leukemia (CML). The recognition of an inactive conformation of Abl, in which a
      catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180
      degrees with respect to the active conformation, underlies the specificity of the
      cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in
      crystal structures of inactive forms of the closely related Src kinases, and
      imatinib does not inhibit c-Src. We present a structure of the kinase domain of
      Abl, determined in complex with an ATP-peptide conjugate, in which the protein
      adopts an inactive conformation that resembles closely that of the Src kinases.
      An interesting aspect of the Src-like inactive structure, suggested by molecular
      dynamics simulations and additional crystal structures, is the presence of
      features that might facilitate the flip of the DFG motif by providing room for
      the phenylalanine to move and by coordinating the aspartate side chain as it
      leaves the active site. One class of mutations in BCR-Abl that confers resistance
      to imatinib appears more likely to destabilize the inactive Src-like conformation
      than the active or imatinib-bound conformations. Our results suggest that
      interconversion between distinctly different inactive conformations is a
      characteristic feature of the Abl kinase domain.

PMID- 16640461
TI  - Proceedings from the 4th International Workshop on Virtual Rehabilitation,
      Catalina, California, USA, September 2005.

PMID- 16640462
TI  - TIES that BIND: an introduction to domain mapping as a visualization tool for
      virtual rehabilitation.
AB  - The application of virtual reality (VR) to rehabilitation is a young,
      interdisciplinary field where clinical implementation very rapidly follows
      scientific discovery and technological advancement. Implementation is often so
      rapid that demonstration of intervention efficacy by investigators, and
      establishment of research and development priorities by funding bodies tend to be
      more reactive than proactive. An examination of the dynamic unfolding of the
      history of our young discipline may help us recognize the facilitators of current
      practice and identify the barriers that limit greater progress. This paper
      presents a first step towards the examination of the past and future growth of VR
      based rehabilitation by presenting the use of concept maps to explore the
      publication history of application of VR to rehabilitation.

PMID- 16640463
TI  - Feasibility, motivation, and selective motor control: virtual reality compared to
      conventional home exercise in children with cerebral palsy.
AB  - Children with cerebral palsy (CP) have difficulty controlling and coordinating
      voluntary muscle, which results in poor selective control of muscle activity.
      Children with spastic CP completed ankle selective motor control exercises using
      a virtual reality (VR) exercise system and conventional (Conv) exercises. Ankle
      movements were recorded with an electrogoniometer. Children and their parents
      were asked to comment on their interest in the exercise programs. Greater fun and
      enjoyment were expressed during the VR exercises. Children completed more
      repetitions of the Conv exercises, but the range of motion and hold time in the
      stretched position were greater during VR exercises. These data suggest that
      using VR to elicit or guide exercise may improve exercise compliance and enhance
      exercise effectiveness.

PMID- 16640464
TI  - Integrating haptic-tactile feedback into a video-capture-based virtual
      environment for rehabilitation.
AB  - Video-capture virtual reality (VR) systems are gaining popularity as intervention
      tools. To date, these platforms offer visual and audio feedback but do not
      provide haptic feedback. We contend that adding haptic feedback may enhance the
      quality of intervention for various theoretical and empirical reasons. This study
      aims to integrate haptic-tactile feedback into a video capture system (GX VR),
      which is currently applied for rehabilitation. The proposed multi-modal system
      can deliver audio-visual as well as vibrotactile feedback. The latter is provided
      via small vibratory discs attached to the patient's limbs. This paper describes
      the system, the guidelines of its design, and the ongoing usability study.

PMID- 16640465
TI  - Reaching within video-capture virtual reality: using virtual reality as a motor
      control paradigm.
AB  - We have developed a virtual reality (VR) system that integrates a three
      dimensional tracking device with a video-capture VR platform to record upper limb
      movements. The influence of target velocity on planning and execution of reaching
      movements was studied in five healthy subjects. Our initial results suggest that
      a target's velocity is considered when planning an interceptive action and that a
      hand reaching toward a moving virtual target is controlled in a similar way to
      how it is in the real visual environment.

PMID- 16640466
TI  - Virtual reality in the rehabilitation of the upper limb after stroke: the user's
      perspective.
AB  - Our group has developed a relatively low-cost virtual reality (VR) system for
      rehabilitation of the upper limb following stroke. Our system is immersive in
      that the participant views a representation of their arm and hand, reaching and
      retrieving objects in the virtual environment (VE), through a head-mounted
      display (HMD). This is thought to increase the participant's sense of presence in
      the VE and may lead to improved rehabilitation outcomes. However, use of
      immersion, particularly with our low-cost system, may increase the incidence of
      side effects reported. Therefore, the aim of this project was to assess the
      interaction of healthy users and those following stroke, in terms of their
      experience of presence in the VE and the rate of self-reported side effects.
      Differences in rates of perceived exertion, levels of enjoyment, and sense of
      control between both groups were also explored.

PMID- 16640467
TI  - Usability of the remote console for virtual reality telerehabilitation: formative
      evaluation.
AB  - The Remote Console (ReCon) is a telerehabilitation application that allows
      therapists to remotely communicate with patients while monitoring and controlling
      their virtual rehabilitation exercises. It provides therapists visual feedback of
      patients' movements, their exercise simulations replicated in real time and with
      tools to conduct training without a face-to-face session. The Recon underwent a
      formative evaluation (a type of usability engineering methodology) used to refine
      its design. Five physical therapists from different practice settings acted as
      representative users. During the evaluation, these users made errors related to
      manipulation and finding and understanding controls. Technical issues with the
      server and audio communication were identified. These findings were used to fine
      tune the ReCon system.

PMID- 16640468
TI  - The Rutgers Arm, a rehabilitation system in virtual reality: a pilot study.
AB  - Stroke is one of the leading causes of death and disability worldwide. Its
      prevalence calls for innovative rehabilitation methods. The Rutgers Arm is a
      novel upper extremity rehabilitation system consisting of a low-friction table,
      three-dimensional (3D) tracker, custom forearm support, PC workstation, library
      of Java 3D virtual reality (VR) exercises, clinical database module, and a tele
      rehabilitation extension. The system was tested on a chronic stroke subject,
      under local and tele-rehabilitation conditions, over 5 weeks of training. Results
      show improvements in arm motor control and shoulder range of motion,
      corresponding to improved Fugl-Meyer test scores. Exercise duration, level of
      difficulty, and patient motivation were maintained under tele-rehabilitaion. A 1
      week retention trial showed that gains were maintained.

PMID- 16640469
TI  - Responses to a virtual reality grocery store in persons with and without
      vestibular dysfunction.
AB  - People with vestibular dysfunction often complain of having difficulty walking in
      visually complex environments. Virtual reality (VR) may serve as a useful
      therapeutic tool for providing physical therapy to these people. The purpose of
      this pilot project was to explore the ability of people with and without
      vestibular dysfunction to use and tolerate virtual environments that can be used
      in physical therapy. We have chosen grocery store environments, which often
      elicit complaints from patients. Two patients and three control subjects were
      asked to stand and navigate in VR grocery stores while finding products.
      Perceived discomfort, simulator sickness symptoms, distance traveled, and speed
      of head movement were recorded. Symptoms and discomfort increased in one subject
      with vestibular dysfunction. The older subjects traveled a shorter distance and
      had greater speed of head movements compared with young subjects. Environments
      with a greater number of products resulted in more head movements and a shorter
      distance traveled.

PMID- 16640470
TI  - A treadmill and motion coupled virtual reality system for gait training post
      stroke.
AB  - A virtual reality (VR)-based locomotor training system has been developed for
      gait rehabilitation post-stroke. The system consists of a self-paced treadmill
      mounted onto a 6-degrees-of-freedom motion platform. Virtual environments (VEs)
      that are synchronized with the speed of the treadmill and the motions of the
      platform are rear-projected onto a screen in front of the walking subject. A
      feasibility study was conducted to test the capability of two stroke patients and
      one healthy control to be trained with the system. Three VE scenarios (corridor
      walking, street crossing, and park stroll) were woven into a gait-training
      program that provided three levels of complexity (walking speed, slopes,
      collision avoidances), progression criteria (number of successful trials) and
      knowledge of results. Results show that, with practice, patients can effectively
      increase their gait speed as demanded by the task and adapt their gait with
      respect to the change in physical terrain. However, successful completion of
      tasks requiring adaptation to increasing demands related to speed and physical
      terrains does not necessarily predict the patient's ability to anticipate and
      avoid collision with obstacles during walking. This feasibility study
      demonstrates that persons with stroke are able to adapt to this novel VR system
      and be immersed in the VEs for gait training.

PMID- 16640471
TI  - Influences of the perception of self-motion on postural parameters.
AB  - We examined how spatial and temporal characteristics of the perception of self
      motion, generated by constant velocity visual motion, was reflected in
      orientation of the head and whole body of young adults standing in a CAVE, a
      virtual environment that presents wide field of view stereo images with context
      and texture. Center of pressure responses from a force plate and perception of
      self-motion through orientation of a hand-held wand were recorded. The influence
      of the perception of self-motion on postural kinematics differed depending upon
      the plane and complexity of visual motion. Postural behaviors generated through
      the perception of self-motion appeared to contain a confluence of the cortically
      integrated visual and vestibular signals and of other somatosensory inputs. This
      would suggest that spatial representation during motion in the environment is
      modified by both ascending and descending controls. We infer from these data that
      motion of the visual surround can be used as a therapeutic tool to influence
      posture and spatial orientation, particularly in more visually sensitive
      individuals following central nervous system (CNS) impairment.

PMID- 16640472
TI  - Immersive virtual reality as a rehabilitative technology for phantom limb
      experience: a protocol.
AB  - This paper describes a study protocol to investigate the use of immersive virtual
      reality as a treatment for amputees' phantom limb pain. This work builds upon
      prior research using mirror box therapy to induce vivid sensations of movement
      originating from the muscles and joints of amputees' phantom limbs. The present
      project transposes movements of amputees' anatomical limbs into movements of a
      virtual limb presented in the phenomenal space of their phantom limb. It is
      anticipated that the protocol described here will help reduce phantom limb pain.

PMID- 16640473
TI  - Motor training in the manipulation of flexible objects in haptic environments.
AB  - A system with interchangeable constraints for studying skillful human movements
      via haptic displays is presented. It is shown how this system can be applied to
      the analysis of reaching movements in the manipulation of flexible objects. In
      the experiment, progress in arm motor training is considered for several
      subjects. Experimental data are obtained for slow, moderate, and fast movements.
      Future applications of the system and its limitations are discussed.

PMID- 16640474
TI  - Using virtual environment to improve spatial perception by people who are blind.
AB  - Mental mapping of spaces, and of the possible paths for navigating these spaces,
      is essential for the development of efficient orientation and mobility skills.
      Visual ability is a crucial component to effective mental mapping. People who are
      blind consequently find it difficult to generate useful mental maps of spaces and
      navigate competently within them. The research studies reported in this paper
      assume that the supply of appropriate spatial information through compensatory
      sensorial channels as an alternative to the visual channel may contribute to the
      anticipatory mental mapping of unknown spaces and consequently may improve
      spatial performance for people who are blind.

PMID- 16640475
TI  - The Jerusalem TeleRehabilitation System, a new low-cost, haptic rehabilitation
      approach.
AB  - Survivors of brain injury or stroke can improve movement ability with intensive,
      supervised practice. Since the hours of supervised therapy with a physical or
      occupational therapist are limited, telerehabilitation will enable patients to
      greatly expand the hours that they practice therapeutic exercises. The Jerusalem
      TeleRehabilitation System (JTRS) consists of patient and therapist systems plus a
      central server and database connected via the internet. The system can work in
      two modes: (1) a cooperative mode in which the therapist and patient are online
      at the same time, and (2) a stand-alone mode in which the patient uses the system
      on his own. In both cases, the system will monitor the status and progress of the
      patient and various parameters of his movement abilities, and prepare reports for
      the patient and for the therapist. From the clinic, the therapist will be able to
      change the screen seen by the patient and change the level and types of tasks, as
      needed. Compared to existing systems, our system will have the following
      advantages: (1) inexpensive and easy to use; (2) remote monitoring and control of
      the patient's computer by the therapist in the clinic; (3) more detailed analysis
      of patient status and progress; (4) a "smart" system which self-adapts to the
      patient's capabilities in real time, increasing or decreasing the difficulty of
      the exercise as needed; and (5) a central, international database which, by
      gathering data on many patients over time, will provide the basis for "smart"
      therapy and will also facilitate coordinated multicenter research studies.

PMID- 16640476
TI  - Human Experience Modeler: context-driven cognitive retraining to facilitate
      transfer of learning.
AB  - We describe a cognitive rehabilitation mixed-reality system that allows
      therapists to explore natural cuing, contextualization, and theoretical aspects
      of cognitive retraining, including transfer of training. The Human Experience
      Modeler (HEM) mixed-reality environment allows for a contextualized learning
      experience with the advantages of controlled stimuli, experience capture and
      feedback that would not be feasible in a traditional rehabilitation setting. A
      pilot study for testing the integrated components of the HEM is discussed where
      the participant presents with working memory impairments due to an aneurysm.

PMID- 16640477
TI  - Application of virtual reality graphics in assessment of concussion.
AB  - Abnormal balance in individuals suffering from traumatic brain injury (TBI) has
      been documented in numerous recent studies. However, specific mechanisms causing
      balance deficits have not been systematically examined. This paper demonstrated
      the destabilizing effect of visual field motion, induced by virtual reality
      graphics in concussed individuals but not in normal controls. Fifty five student
      athletes at risk for concussion participated in this study prior to injury and 10
      of these subjects who suffered MTBI were tested again on day 3, day 10, and day
      30 after the incident. Postural responses to visual field motion were recorded
      using a virtual reality (VR) environment in conjunction with balance (AMTI force
      plate) and motion tracking (Flock of Birds) technologies. Two experimental
      conditions were introduced where subjects passively viewed VR scenes or actively
      manipulated the visual field motion. Long-lasting destabilizing effects of visual
      field motion were revealed, although subjects were asymptomatic when standard
      balance tests were introduced. The findings demonstrate that advanced VR
      technology may detect residual symptoms of concussion at least 30 days post
      injury.

PMID- 16640478
TI  - Virtual reality pencil and paper tests for neglect: a protocol.
AB  - Hemispatial neglect is a common disorder that can occur after a lesion in the
      right hemisphere. Its main characterization is the difficulty in processing
      visual stimuli emanating from the space contralateral to the lesion. Pencil and
      paper tests (such as target cancellation, line bisection, or drawing copy) are
      used to diagnose neglect. We propose using virtual reality technology and haptic
      force feedback to enhance pencil and paper tests. Our system can track the
      patients' eye-gaze and their hand movements. Also, the efficiency of several
      techniques used to decrease the neglect in different sensory spaces are
      investigated.

PMID- 16640479
TI  - Virtual and physical toys: open-ended features for non-formal learning.
AB  - This paper examines the integrated toy--both physical and virtual--as an
      essential resource for collaborative learning. This learning incorporates
      rehabilitation, training, and education. The data derived from two different
      cases. Pedagogical issues related to non-formal learning and open-ended features
      of design are discussed. Findings suggest that social, material, and expressive
      affordances constitute a base for an alterative interface to encourage children's
      play and learning.

PMID- 16640480
TI  - Three-dimensional virtual environments for blind children.
AB  - Information technologies are increasingly helping to integrate and socially
      include people with visual disabilities. Computing technologies have contributed
      grandly to attain this goal through innovative techniques and applications.
      Virtual environments, I/O interfaces, and sound based applications altogether
      with usability and cognitive impact studies are some of the most used research
      designs for children with visual disabilities. This study presents the design and
      usability evaluation of three-dimensional (3D) interactive environments for
      children with visual disabilities. We introduce AudioChile and AudioVida,
      interactive virtual environments that can be navigated through 3D sound to
      enhance spatiality and immersion throughout the environments 3D sound is used to
      orientate, to avoid obstacles, and to identify the position of diverse personages
      and objects within the environment. Usability evaluation results indicated that
      sound can be fundamental for attention and motivation purposes during
      interaction.

PMID- 16640481
TI  - Effectiveness of virtual reality for pediatric pain distraction during i.v.
      placement.
AB  - The objective of this study was to test the efficacy and suitability of virtual
      reality (VR) as a pain distraction for pediatric intravenous (i.v.) placement.
      Twenty children (12 boys, 8 girls) requiring i.v. placement for a magnetic
      resonance imaging/computed tomography (MRI/CT) scan were randomly assigned to two
      conditions: (1) VR distraction using Street Luge (5DT), presented via a head
      mounted display, or (2) standard of care (topical anesthetic) with no
      distraction. Children, their parents, and nurses completed self-report
      questionnaires that assessed numerous health-related outcomes. Responses from the
      Faces Pain Scale-Revised indicated a fourfold increase in affective pain within
      the control condition; by contrast, no significant differences were detected
      within the VR condition. Significant associations between multiple measures of
      anticipatory anxiety, affective pain, i.v. pain intensity, and measures of past
      procedural pain provided support for the complex interplay of a multimodal
      assessment of pain perception. There was also a sufficient amount of evidence
      supporting the efficacy of Street Luge as a pediatric pain distraction tool
      during i.v. placement: an adequate level of presence, no simulator sickness, and
      significantly more child-, parent-, and nurse-reported satisfaction with pain
      management. VR pain distraction was positively endorsed by all reporters and is a
      promising tool for decreasing pain, and anxiety in children undergoing acute
      medical interventions. However, further research with larger sample sizes and
      other routine medical procedures is warranted.

PMID- 16640482
TI  - Simulating social interaction to address deficits of autistic spectrum disorder
      in children.
AB  - Autistic spectrum disorder (ASD) is diagnosed on the basis of impairment in
      reciprocal social interaction and language, and rigidity of behavior. This brief
      paper describes the development of an experimental intervention for preschool
      children newly diagnosed with ASD. The rationale for this intervention is the
      hypothesis that failure to attend to social cues in very early life, of itself,
      may bear a large share of responsibility for core social and communicative
      deficits. The intervention, therefore, uses eye-tracking to monitor and trigger
      rewards for attention to facial expression and direction of gaze.

PMID- 16640483
TI  - Starting research in interaction design with visuals for low-functioning children
      in the autistic spectrum: a protocol.
AB  - On starting to think about interaction design for low-functioning persons in the
      autistic spectrum (PAS), especially children, one finds a number of questions
      that are difficult to answer: Can we typify the PAS user? Can we engage the user
      in interactive communication without generating frustrating or obsessive
      situations? What sort of visual stimuli can we provide? Will they prefer
      representational or abstract visual stimuli? Will they understand three
      dimensional (3D) graphic representation? What sort of interfaces will they
      accept? Can we set ambitious goals such as education or therapy? Unfortunately,
      most of these questions have no answer yet. Hence, we decided to set an
      apparently simple goal: to design a "fun application," with no intention to reach
      the level of education or therapy. The goal was to be attained by giving the
      users a sense of agency--by providing first a sense of control in the interaction
      dialogue. Our approach to visual stimuli design has been based on the use of
      geometric, abstract, two-dimensional (2D), real-time computer graphics in a full
      body, non-invasive, interactive space. The results obtained within the European
      funded project MultiSensory Environment Design for an Interface between Autistic
      and Typical Expressiveness (MEDIATE) have been extremely encouraging.

PMID- 16640484
TI  - Virtual reality assessment of medication compliance in patients with
      schizophrenia.
AB  - Medication compliance is essential to treating the symptoms of schizophrenia
      effectively. This study utilized a virtual reality (VR) apartment paradigm to
      assess medication compliance behaviors in 25 patients with schizophrenia and in
      16 healthy control subjects. Participants were assigned a prescription consisting
      of three medications and were asked to self-administer this regimen in 15 min.
      Results demonstrate that patients had considerably more difficulty in complying
      with the medication regimen than did controls. They manifested significantly more
      quantitative errors, and were much less accurate in consuming the medications at
      the assigned time. Significant differences in performance between these groups
      were also evidenced by a variety of validated neuropsychological measures.
      Correlations between the data may suggest a convergent validity for this new VR
      task. Future research will investigate the validity of this task in predicting
      additional measures of psychosocial functioning.

PMID- 16640485
TI  - Reality check: the role of realism in stress reduction using media technology.
AB  - There is a growing interest in the use of virtual and other mediated environments
      for therapeutic purposes. However, in the domain of restorative environments,
      virtual reality (VR) technology has hardly been used. Here the tendency has been
      to use mediated real environments, striving for maximum visual realism. This use
      of photographic material is mainly based on research in aesthetics judgments that
      has demonstrated the validity of this type of simulations as representations of
      real environments. Thus, restoration therapy is developing under the untested
      assumption that photorealistic images have the optimal level of realism, while in
      therapeutic applications 'experiential realism' seems to be the key rather than
      visual realism. The present paper discusses this contrast and briefly describes
      data of three studies aimed at exploring the importance and meaning of realism in
      the context of restorative environments.

PMID- 16640486
TI  - Hippocampus function predicts severity of post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is often accompanied by memory problems and
      abnormal brain structure, particularly within the hippocampus. We implemented a
      cross-species, hippocampal-dependent task--the virtual Morris Water task--to
      assess hippocampal function in people with PTSD and age-matched controls during
      functional magnetic resonance imaging (fMRI). Performance on the task was
      equivalent between the groups. However, when correlating fMRI-derived hippocampal
      activity during this task with PTSD severity, we observe a -0.84 correlation,
      indicating that those with reduced hippocampal activity show more severe PTSD
      symptoms. This correlation is not explained by differences in task performance,
      IQ, duration since trauma, nor time with PTSD. Hence, PTSD severity is predicted
      by functionally assessing the hippocampus using the virtual Morris water task,
      suggesting that this task may be used to identify those at risk for developing
      PTSD following a trauma.

PMID- 16640487
TI  - BusWorld: designing a virtual environment for post-traumatic stress disorder in
      Israel: a protocol.
AB  - A number of carefully controlled studies have documented the effectiveness of
      traditional imaginal exposure for the treatment of post-traumatic stress disorder
      (PTSD). Virtual reality (VR) exposure therapy is based on a similar logic but
      rather than self-generating imagery, patients wear a VR helmet and go into a
      three-dimensional (3-D) computer generated virtual world to help them gain access
      to their memory of the traumatic event. Recent preliminary research has shown
      that some patients who fail to respond to traditional therapy benefit from
      virtual reality exposure therapy, presumably because VR helps the patient become
      emotionally engaged while recollecting/recounting/re-interpreting/emotionally
      processing what happened during the traumatic event. The present paper presents a
      brief overview of a new VR World we developed to provide virtual reality therapy
      for terrorist bus bombing victims in Israel, and a brief description of our
      research protocol and measures (for details, see www.vrpain.com).

PMID- 16640488
TI  - Simulation and virtual reality in medical education and therapy: a protocol.
AB  - Continuing medical education has historically been provided primarily by didactic
      lectures, though adult learners prefer experiential or self-directed learning.
      Young physicians have extensive experience with computer-based or "video" games,
      priming them for medical education--and treating their patients--via new
      technologies. We report our use of standardized patients (SPs) to educate
      physicians on the diagnosis and treatment of biological and chemical warfare
      agent exposure. We trained professional actors to serve as SPs representing
      exposure to biological agents such as anthrax and smallpox. We rotated workshop
      participants through teaching stations to interview, examine, diagnose and treat
      SPs. We also trained SPs to simulate a chemical mass casualty (MASCAL) incident.
      Workshop participants worked together to treat MASCAL victims, followed by
      discussion of key teaching points. More recently, we developed computer-based
      simulation (CBS) modules of patients exposed to biological agents. We compare the
      strengths and weaknesses of CBS vs. live SPs. Finally, we detail plans for a
      randomized controlled trial to assess the efficacy of virtual reality (VR)
      exposure therapy compared to pharmacotherapy for post-traumatic stress disorder
      (PTSD). PTSD is associated with significant disability and healthcare costs,
      which may be ameliorated by the identification of more effective therapy.

PMID- 16640489
TI  - Virtual reality applications to agoraphobia: a protocol.
AB  - Recently, educators and instructional designers have focused on the development
      and implementation of virtual learning environments that effectively combine
      theoretical and applied knowledge to teach university students. One of the trusts
      of the Psychology Virtual Teaching Laboratory in collaboration with the IXTLI
      observatory is to develop dissemination programs to promote the insertion of
      virtual reality (VR) technologies applied to rehabilitation in their clinical
      practice. This paper describes the development of (1) agoraphobia VR learning
      objects to be use as a teaching support tools in class and (2) a multimedia
      teaching program that incorporate digital video and VR scenarios address to
      students in the field of mental health. Promotion among professors and students
      about the use of this technology will allow us to initiate research in our
      country as well as to validate contextualized applications for our culture,
      therefore contributing with new advances in this field.

PMID- 16640491
TI  - CyberEurope. Seventh Framework Programme (FP7): health.

PMID- 16640492
TI  - Cost-effectiveness of drug-eluting stents: real-world scrutiny of the BASKET
      trial of real-world usage.
AB  - This editorial examines incremental cost-effectiveness analysis as a decision
      making tool to guide the allocation of scarce financial resources. BASKET (Basel
      Stent Kosten Effektivitats Trial) evaluated the cost-effectiveness of drug
      eluting stents in a real-world setting. Results of this study are examined in
      relation to similar assessments and alternative plausible assumptions are
      explored and presented in the context of real-world sensitivity analysis.

PMID- 16640493
TI  - Nanoparticle-aptamer bioconjugates for cancer targeting.
AB  - The combination of targeted drug delivery and controlled-release technology may
      pave the road for more effective yet safer chemotherapeutic options for cancer
      therapy. Drug-encapsulated polymeric nanoparticle-aptamer bioconjugates represent
      an emerging technology that can facilitate the delivery of chemotherapeutics to
      primary and metastatic tumours. Aptamers are short nucleic acid molecules with
      binding properties and biochemical characteristics that may make them suitable
      for use as targeting molecules. The goal of this review is to summarise the key
      components that are required for creating effective cancer targeting nanoparticle
      aptamer bioconjugates. The field of controlled release and the structure and
      properties of aptamers, as well as the criteria for constructing effective
      conjugates, will be discussed.

PMID- 16640494
TI  - Polymeric nanoparticles for gene delivery.
AB  - Since the evolution of the concept of gene therapy, delivering therapeutic genes
      to the diseased cells has been a major challenge. Although viral vectors have
      been shown to be efficient in delivering genes, the issue of their safety is
      still to be solved. Meanwhile, the field of developing nonviral expression
      vectors has seen considerable progress. As compared with viruses, these are
      relatively safe but are confronted with the problem of poor transfection
      efficiency. With the growing understanding of the biology of gene transfection,
      and the continued efforts at enhancing the efficiency of nonviral expression
      vectors, it could soon become a preferred option for human gene therapy. In this
      review, the potential of polymeric nanoparticles as a gene expression vector is
      discussed. Furthermore, the importance of understanding the pathophysiology of
      disease conditions in developing gene expression vectors is discussed in Section
      6.

PMID- 16640495
TI  - Immunostimulatory colloidal delivery systems for cancer vaccines.
AB  - Cancer vaccine delivery is a multidisciplinary scientific field that is currently
      undergoing rapid development. An important component of cancer vaccines is the
      development of novel vaccine delivery strategies, such as colloidal
      immunostimulatory delivery systems. The importance of formulation strategies for
      cancer vaccines can be explained by the poor immunogenicity of tumour antigens.
      Colloidal vaccine delivery systems modify the kinetics, body distribution, uptake
      and release of the vaccine. This review explores recent research that is directed
      towards more targeted treatments of cancer through to colloidal vaccine delivery
      systems. Widely investigated carrier systems include polymeric micro- and
      nanoparticles, liposomes, archaeal lipid liposomes (archaeosomes), immune
      stimulating complexes and virus-like particles. These systems are evaluated in
      terms of their formulation techniques, immunological mechanisms of action as well
      as the potential and limitations of such colloidal systems in the field of cancer
      vaccines.

PMID- 16640496
TI  - Inhibition of tumour metastasis by targeted delivery of antioxidant enzymes.
AB  - Metastasis is one of the most harmful aspects of malignant neoplasm. Interaction
      of tumour cells with normal cells such as tissue macrophages may generate
      reactive oxygen species, which would affect various aspects of tumour metastasis.
      Reactive oxygen species cause damage to both tumour and normal cells and some of
      them, especially hydrogen peroxide, can also act as intracellular second
      messengers at sublethal concentrations to increase the transcription of various
      genes, which can then accelerate the proliferation of tumour cells in metastatic
      colonies. Therefore, eliminating hydrogen peroxide is one approach to inhibiting
      tumour metastasis. In this article, the roles of reactive oxygen species in
      tumour metastasis are reviewed, and the strategies to inhibit tumour metastasis
      by the targeted delivery of catalase, an enzyme that detoxifies hydrogen
      peroxide, are discussed.

PMID- 16640497
TI  - Convection-enhanced delivery of targeted toxins for malignant glioma.
AB  - Malignant gliomas represent a difficult treatment challenge for the neuro
      oncologist and the neurosurgeon. These tumours continue to be refractory to
      standard therapies, such as surgery, radiotherapy and conventional chemotherapy,
      and new therapeutic options are clearly needed. Therefore, investigators have
      recently taken a new direction and started to engineer compounds such as
      recombinant cytotoxins, antiangiogenesis factors and genetic delivery vectors.
      However, these promising new agents are all dependent on an effective
      distribution method in order to bypass the blood-brain barrier. Convection
      enhanced delivery (CED) allows for the administration of targeted toxins and
      other agents directly into the brain at the site of a tumour via catheters placed
      with the aid of stereotactic or image-guided surgery. The use of this technique
      is gaining momentum as a newly accepted treatment modality where little else has
      produced durable results in the fight against gliomas. Direct intratumoural
      infusion was first performed in nude mouse flank tumour models of human malignant
      glioma. After significant testing in preclinical animal studies, this method of
      delivery was followed by the successful demonstration of in vivo efficacy in
      Phase I and II clinical trials. Currently, this technique is being used in the
      investigational setting at academic medical centres where investigators are
      starting to define the best practice for CED. Fundamental issues in this method
      of delivery such as rate of infusion, cannula size, infusate concentration and
      tissue-cannula sealing time shape the current discussion in the literature.
      Targeted toxin therapy represents one of the newest and most promising treatments
      for this unfortunate patient population, with proven clinical efficacy
      administered through CED, which is a novel approach to drug delivery.

PMID- 16640498
TI  - Controlled-release microchips.
AB  - Efficient drug delivery remains an important challenge in medicine: continuous
      release of therapeutic agents over extended time periods in accordance with a
      predetermined temporal profile; local delivery at a constant rate to the tumour
      microenvironment to overcome much of the systemic toxicity and to improve
      antitumour efficacy; improved ease of administration, and increasing patient
      compliance required are some of the unmet needs of the present drug delivery
      technology. Microfabrication technology has enabled the development of novel
      controlled-release microchips with capabilities not present in the current
      treatment modalities. In this review, the current status and future prospects of
      different types of controlled-release microchips are summarised and analysed with
      reference to microneedle-based microchips, as well as providing an in-depth focus
      on microreservoir-based and nanoporous microchips.

PMID- 16640499
TI  - Drug delivery strategies using polysaccharidic gels.
AB  - Hydrogels are hydrophilic polymeric networks, with chemical or physical
      crosslinks, that are capable of swell and can retain a large amount of water.
      Among the numerous types of macromolecules that can be used for hydrogel
      formation, polysaccharides show very attractive advantages in comparison to
      synthetic polymers. They are widely present in living organisms, are usually
      abundant and show a number of peculiar physicochemical properties; furthermore,
      these macromolecules are, in most cases, non-toxic, biocompatible and can be
      obtained from renewable sources. For these reasons, polysaccharides seem to be
      particularly suitable for different applications in the wide field of
      pharmaceutics. As examples of the studies that have been carried out on this
      topic, this review will focus on two polysaccharides, alginate and xyloglucan.
      Alginate has been, and still is, extensively investigated and has numerous
      industrial applications, whereas xyloglucan was chosen because, although it has
      been much less studied, it shows interesting properties that should find
      important practical uses in the near future. The possible advantages of physical
      gels over those that are chemically crosslinked are also discussed.

PMID- 16640500
TI  - Transdermal delivery of beta-blockers.
AB  - Beta-adrenoceptor blocking drugs (beta-blockers) are one of the most frequently
      used class of cardiovascular drugs that are mainly used in conventional dosage
      forms., which have their own limitations including hepatic first-pass metabolism,
      high incidence of adverse effects due to variable absorption profiles, higher
      frequency of administration and poor patient compliance. Essentially, attempts
      have been made to develop novel drug delivery systems for beta-blockers,
      including transdermal delivery systems, to circumvent the drawbacks of
      conventional drug delivery. However, so far none of the beta-blocker drugs have
      been marketed as transdermal delivery systems. Nevertheless, there have been
      noteworthy research endeavours worldwide at the laboratory level to investigate
      the skin permeation and to develop transdermal formulations of beta-blockers
      including: propranolol, metoprolol, atenolol, timolol, levobunolol, bupranolol,
      bopindolol, mepindolol, sotalol, labetolol, pindolol, acebutolol and oxprenolol.
      Innovative research exploiting penetration-enhancing strategies, such as
      iontophoresis, electroporation, microneedles and sonophoresis, holds promise for
      the successful use of these drugs as consumer-friendly transdermal dosage forms
      in clinical practice. This paper presents an overview of the transdermal research
      on this important class of drugs.

PMID- 16640501
TI  - Drug delivery across the blood-brain barrier: why is it difficult? how to measure
      and improve it?
AB  - The development of drugs that act in the CNS has been significantly impeded by
      the difficulty of delivering them across the blood-brain barrier (BBB). This
      article aims to provide the reader with a critical overview of important issues
      in the discovery and development of drugs that need to enter the brain to elicit
      pharmacological activity, focusing particularly on i) the role of drug
      transporters in brain permeation and how to manipulate them to enhance drug brain
      bioavailability; ii) the successful application, limitations and challenges of
      commonly used in vitro and in vivo methodologies for measuring drug transport
      across the BBB, and iii) a discussion of recently developed strategies (e.g.,
      modulation of efflux transporters by chemical inhibitors and the employment of
      delivery vectors taking advantage of native transport systems at the BBB) for
      facilitating drug penetration into the brain.

PMID- 16640502
TI  - The hair follicle and its stem cells as drug delivery targets.
AB  - The hair follicle is a skin appendage with a complex structure containing many
      cell types that produce highly specialised proteins. The hair follicle is in a
      continuous cycle: anagen is the hair growth phase, catagen the involution phase
      and telogen is the resting phase. The follicle offers many potential therapeutic
      targets. Hoffman and colleagues have pioneered hair-follicle-specific targeting
      using liposomes to deliver small and large molecules, including genes. They have
      also pioneered ex vivo hair-follicle targeting with continued expression of the
      introduced gene following transplantation. Recently, it has been discovered that
      hair follicle stem cells are highly pluripotent and can form neurons, glial cells
      and other cell types, and this has suggested that hair follicle stem cells may
      serve as gene therapy targets for regenerative medicine.

PMID- 16640503
TI  - ICS-283: a system for targeted intravenous delivery of siRNA.
AB  - ICS-283 was developed within Intradigm Corporation as a system that is designed
      for the systemic delivery of therapeutic small interfering (siRNA) to sites of
      pathological angiogenesis. The non-viral siRNA delivery system is based on
      synthetic nanoparticles, known as Targe (Intradigm Corporation), which functions
      as a broad-platform technology to deliver siRNA to specific target cells in
      diseased tissues. The system is constructed to incorporate different
      functionalities that address critical needs for successful nucleic acid delivery.
      The TargeTran synthetic vector is a self-assembling, layered nanoparticle that
      protects and targets siRNA to specific cell types in pathological tissues. At
      present, ICS-283 is the only antiangiogenic siRNA delivery system that is
      designed for intravenous administration to treat angiogenesis-driven diseases.

PMID- 16640504
TI  - A preliminary investigation demonstrating the effect of quercetin on the
      expression of genes related to cell-cycle arrest, apoptosis and xenobiotic
      metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray.
AB  - The role of the natural dietary flavonoid chemical quercetin (an antioxidant) in
      the prevention and treatment of colon cancer is receiving a great deal of
      attention. However, little is known about the molecular mechanisms of action of
      this flavonoid. In the present study, whole genome DNA microarrays were used to
      evaluate the effect of quercetin on gene expression in the CO115 colon
      adenocarcinoma cell line with the completely deleted chromosome 18 harbouring the
      SMAD4 tumour-suppressor gene related to colon carcinogenesis. The study
      demonstrated that quercetin, widely present in fruit and vegetables, inhibited
      the growth of CO115 cells at 100 microM concentration in both the G(1)/S and the
      G(2)/M phases by modulating cell-cycle and apoptosis-related genes. Differential
      changes in accumulation of transcripts analysed for cells treated with 100 microM
      quercetin for 24 and 48 h in three independent repeated experiments revealed 5060
      7000 differentially expressed genes. This means that quercetin probably does have
      a broad modulatory effect on gene expression in colon cancer. Out of these
      differentially expressed genes, the expression of 35 and 23 unique set of genes
      involved in cell-cycle control, apoptosis and xenobiotic metabolism were
      significantly altered after 24 and 48 h quercetin treatment respectively. Our
      results represent a novel aspect of the biological profile of quercetin that
      induces cell-cycle arrest through modulation of cell-cycle-related and apoptosis
      genes. The present study demonstrates a new step in elucidating the underlying
      molecular mechanisms of the antitumour action of quercetin, which could become a
      chemopreventive or chemotherapeutic agent for colon cancer.

PMID- 16640505
TI  - Modification of the pulmonary renin-angiotensin system and lung structural
      remodelling in congestive heart failure.
AB  - Lung structural remodelling, characterized by myofibroblast proliferation and
      collagen deposition, contributes to impaired functional capacity in CHF
      (congestive heart failure). As the lung is the primary site for the formation of
      Ang II (angiotensin II), local modifications of this system could contribute to
      lung remodelling. Rats with CHF, induced following myocardial infarction (MI) via
      coronary artery ligation, were compared with sham-operated controls. The MI group
      developed lung remodelling as confirmed by morphometric measurements and
      immunohistochemistry. Pulmonary Ang II concentrations increased more than 6-fold
      (P<0.01), and AT1 (Ang II type 1) receptor expression was elevated by 3-fold
      (P<0.01) with evidence of distribution in myofibroblasts. AT2 (Ang II type 2)
      receptor expression was unchanged. In isolated lung myofibroblasts, AT1 and AT2
      receptors were expressed, and Ang II stimulated proliferation as measured by
      [3H]thymidine incorporation. In normal rats, chronic intravenous infusion of Ang
      II (0.5 mg.kg(-1) of body weight.day(-1)) for 28 days significantly increased
      mean arterial pressure (P<0.05), without pulmonary hypertension, lung remodelling
      or a change in AT1 receptor expression. We conclude that there is a modification
      of the pulmonary renin-angiotensin system in CHF, with increased Ang II levels
      and AT1 receptor expression on myofibroblasts. Although this may contribute to
      lung remodelling, the lack of effect of increased plasma Ang II levels alone
      suggests the importance of local pulmonary Ang II levels combined with the effect
      of other factors activated in CHF.

PMID- 16640506
TI  - Structure-function relationships for Schizophyllum commune trehalose
      phosphorylase and their implications for the catalytic mechanism of family GT-4
      glycosyltransferases.
AB  - The cDNA encoding trehalose phosphorylase, a family GT-4 glycosyltransferase from
      the fungus Schizophyllum commune, was isolated and expressed in Escherichia coli
      to yield functional recombinant protein in its full length of 737 amino acids.
      Unlike the natural phosphorylase that was previously obtained as a truncated 61
      kDa monomer containing one tightly bound Mg2+, the intact enzyme produced in E.
      coli is a dimer and not associated with metal ions [Eis, Watkins, Prohaska and
      Nidetzky (2001) Biochem. J. 356, 757-767]. MS analysis of the slow spontaneous
      conversion of the full-length enzyme into a 61 kDa fragment that is fully active
      revealed that critical elements of catalysis and specificity of trehalose
      phosphorylase reside entirely in the C-terminal protein part. Intact and
      truncated phosphorylases thus show identical inhibition constants for the
      transition state analogue orthovanadate and alpha,alpha-trehalose (K(i)
      approximately 1 microM). Structure-based sequence comparison with retaining
      glycosyltransferases of fold family GT-B reveals a putative active centre of
      trehalose phosphorylase, and results of site-directed mutagenesis confirm the
      predicted crucial role of Asp379, His403, Arg507 and Lys512 in catalysis and also
      delineate a function of these residues in determining the large preference of the
      wild-type enzyme for the phosphorolysis compared with hydrolysis of alpha,alpha
      trehalose. The pseudo-disaccharide validoxylamine A was identified as a strong
      inhibitor of trehalose phosphorylase (K(i)=1.7+/-0.2 microM) that displays 350
      fold tighter binding to the enzyme-phosphate complex than the non
      phosphorolysable substrate analogue alpha,alpha-thio-trehalose. Structural and
      electronic features of the inhibitor that may be responsible for high-affinity
      binding and their complementarity to an anticipated glucosyl oxocarbenium ion
      like transition state are discussed.

PMID- 16640507
TI  - Validation of a new automated method for analysis of gated-SPECT images.
AB  - We recently presented a new method for quantification of CArdiac FUnction-
      denoted CAFU--as the first step in the development of an automated method for
      integrated interpretation of gated myocardial perfusion single photon emission
      computed tomography (SPECT) images. The aim of this study was to validate CAFU in
      the assessment of global and regional function of the left ventricle.
      Quantitative gated-SPECT (QGS), the most widely used software package for
      quantification of gated-SPECT images, was used as reference method for the
      measurements of ejection fraction (EF) and ventricular volumes, and visual
      analysis by an experienced physician was used as reference method for the
      measurements of regional wall motion and thickening. Two different groups of
      consecutive patients referred for myocardial perfusion scintigraphy were studied.
      Global function was evaluated in 316 patients and regional function in 49 other
      patients. The studies were performed using a 2-day stress/rest 99 m-Tc-sestamibi
      protocol. A good correlation was found between EF values from QGS and CAFU (EF
      CAFU = 0.84 EF QGS + 13, r = 0.94), but CAFU values were on average 4 EF points
      higher than QGS values. With CAFU the segments with normal thickening according
      to the physician showed significantly higher thickening values (in all parts of
      the myocardium) compared to the segments classified as having abnormal
      thickening. In conclusion, this study demonstrates that CAFU can be used to
      quantify global and regional function in gated-SPECT images. This is an important
      step in our development of an automated method for integrated interpretation of
      gated-SPECT myocardial perfusion scintigraphy studies.

PMID- 16640508
TI  - Patient gender and radiopharmaceutical tracer is of minor importance for the
      interpretation of myocardial perfusion images using an artificial neural network.
AB  - The purpose of this study was to assess the influence of patient gender and
      choice of perfusion tracer on computer-based interpretation of myocardial
      perfusion images. For the image interpretation, an automated method was used
      based on image processing and artificial neural network techniques. A total of
      1000 patients were studied, all referred to the Royal Brompton Hospital in London
      for myocardial perfusion scintigraphy over a period of 1 year. The patients were
      randomized to receive either thallium or one of the two technetium tracers,
      methoxyisobutylisonitrile or tetrofosmin. Artificial neural networks were trained
      with either mixed gender or gender-specific and mixed tracer or tracer-specific
      training sets of different sizes. The performance of the networks was assessed in
      separate test sets, with the interpretation of experienced physicians regarding
      the presence or absence of fixed or reversible defects in the images as the gold
      standard. The neural networks trained with large mixed gender training sets were
      as good as the networks trained with gender-specific data sets. In addition, the
      neural networks trained with large mixed tracer training sets were as good as or
      better than the networks trained with tracer-specific data sets. Our results
      indicate that the influence of patient gender and perfusion tracer are of minor
      importance for the computer-based interpretation of the myocardial perfusion
      images. The differences that occur can be compensated for by larger training
      sets.

PMID- 16640509
TI  - Decision support for the initial triage of patients with acute coronary
      syndromes.
AB  - Early revascularization of acute coronary syndromes improves the prognosis. It is
      of vital importance that the decision to treat the patient is taken as early as
      possible. The aim of this study was (i) to develop an automated tool for the
      analysis of electrocardiograms (ECGs) with regard to changes that indicate
      possible transmural ischaemia and (ii) to assess the influence of the tool on the
      ECG classifications of three interns with less than 12 months of experience in
      ECG reading. An artificial neural network was trained to automatically interpret
      ECGs using 3000 ECGs recorded at an emergency department. Thereafter, the
      performance of the network was evaluated using 1000 test ECGs. In the second
      step, three interns classified these test ECGs twice on different occasions, with
      and without the advice of the neural network. The gold standard was the
      classification made by two experienced cardiologists. On average, the three
      interns showed a sensitivity of 68% at a specificity of 92% without the advice of
      the neural network and a sensitivity of 93% at a specificity of 87% with the
      advice. The neural network itself showed a sensitivity of 95% at a specificity of
      88%. The increase in sensitivity of 23-26% was significant (P<0.001) for all
      three interns. In conclusion, an artificial neural network can be trained to the
      improve performance in the interpretation of ST-segment changes in accordance
      with that of the experienced cardiologists.

PMID- 16640510
TI  - Determination of the ability of high-frequency ECG to estimate left ventricular
      mass in humans, determined by magnetic resonance imaging.
AB  - BACKGROUND: Previous studies have shown a significantly higher correlation
      between left ventricular mass index (LVMi) and high-frequency QRS components (HF
      QRS) than between LVMi and QRS amplitudes in the standard frequency range in
      rabbits. The purpose of the present study was to compare ECG measurements from
      standard and high-frequency ranges with left ventricular mass (LVM) and LVMi
      determined by magnetic resonance imaging in humans. METHODS: Sixty-two normal
      subjects were studied. Signal-averaged ECGs from the 12 standard leads were
      analysed in the standard frequency range (0.05-150 Hz), in the middle (25-100 Hz)
      and high end (50-150 Hz) of the standard frequency range and in the 150-250 Hz
      range. Root-mean square (RMS) values from the HF-QRS and QRS amplitude
      measurements from the standard ECGs were compared with LVM and LVMi. RESULTS: The
      correlations between LVMi and HF-QRS were similar to those between LVMi and
      standard ECG. When regarding LVM, however, the correlations found in the standard
      ECG were higher than those found in HF-QRS. CONCLUSIONS: Contrary to previous
      results in animals, we found in humans no better correlation between HF-QRS and
      LVM/LVMi than between standard ECG and LVM/LVMi.

PMID- 16640511
TI  - Acute effects of caffeine on heart rate variability in habitual caffeine
      consumers.
AB  - During the last years, heart rate variability (HRV) has become a promising risk
      factor for cardiovascular events. However, the effect of caffeine on HRV in
      habitual caffeine consumers has barely been investigated. Therefore, we treated
      30 male habitual caffeine users in a randomized double-blinded crossover study
      design with either placebo, 100 or 200 mg caffeine orally and determined
      parameters of HRV under resting conditions and metronomic breathing. As result,
      we could not detect significant differences in HRV parameters up to 90 min after
      drug ingestion. We conclude that modest amounts of caffeine do not reveal
      negative nor positive effects on HRV within the first 90 min after drug ingestion
      in young and healthy habitual caffeine consumers. However, further research is
      necessary to determine the effects of caffeine on HRV in habitual caffeine users,
      healthy as well as suffering from diabetes, hypertension and postmyocardial
      infarction.

PMID- 16640512
TI  - Radioiodine therapy in hyperthyroid disease: poorer outcome in patients with high
      24 hours radioiodine uptake.
AB  - PURPOSE: To evaluate the importance of 24 h radioiodine uptake (24 h RIU) for the
      outcome of radioiodine treatment of hyperthyroidism. METHODS: Retrospective
      analysis of 72 patients who underwent radioiodine treatment for toxic goiter at
      our outpatient clinic [29 diffuse goiters (DG), 30 toxic multinodular goiters
      (TMG) and 13 toxic adenomas (TA)]. Thyroid status was determined by TSH, fT3 and
      fT4 levels, and outcome was rendered successful when hyperthyroidism was absent.
      Relation between low 24 h RIU (below median) or high 24 h RIU (above or equal to
      median) and outcome was evaluated. RESULTS: Of patients with DG and low 24 h RIU,
      15% remained hyperthyroid, as opposed to 56% of patients with DG and high 24 h
      RIU (P<0.05). Of patients with TMG and low 24 h RIU, none remained hyperthyroid,
      as opposed to 44% of patients with TMG and high 24 h RIU (P<0.01). Of patients
      with TA and low 24 h RIU, none remained hyperthyroid, as opposed to 43% of
      patients with TA and high 24 h RIU (NS, P = 0.19). CONCLUSION: In patients with
      hyperthyroid disease treated with radioiodine the outcome is poorer for patients
      with high 24 h RIU compared with low 24 h RIU measured prior to treatment when
      the radioiodine dose is calculated on the basis of 24 h RIU.

PMID- 16640513
TI  - The central circulation in congestive heart failure non-invasively evaluated with
      dynamic positron emission tomography.
AB  - BACKGROUND: Positron emission tomography (PET) with [15O]-H2O-PET (WAT-PET) or
      [11C]-acetate (AC-PET) quantifies myocardial perfusion and oxidative metabolism,
      but routine clinical use is hampered by the need for additional investigations to
      assess cardiac performance. OBJECTIVE: To apply classical tracer kinetics to
      dynamic PET could provide important haemodynamic parameters. METHODS: First-pass
      PET data were used with indicator dilution techniques to measure stroke volume
      index (SVI). Early pulmonary retention of [11C]-acetate was converted to standard
      uptake values (SUV) (Lung(AC-SUV)). Regional lung water (rLW) content was
      computed from the WAT-PET scan at equilibrium. PET was compared with radionuclide
      angiography and echocardiography in patients with ischaemic cardiomyopathy with
      New York Heart Association class II (n = 10) or III (n = 18) congestive heart
      failure. Elderly male volunteers without heart disease (n = 11) underwent AC-PET
      as controls. RESULTS: SVI with both tracers correlated in patients (r = 0.91,
      P<0.001, estimated standard error = 4 ml m(-2)) and with left ventricular
      ejection fraction (both tracers r>0.6, P<0.001). SVI was significantly different
      between all groups (ANOVA: P<0.001). Lung(AC-SUV) correlated with rLW (r = 0.78,
      P<0.001) and both were elevated in severe heart failure (P<0.05 for both).
      Elevated Lung(AC-SUV) was associated with a restrictive left ventricular (LV)
      filling pattern by Doppler echocardiography. CONCLUSION: Dynamic PET with first
      pass analysis and tracers of myocardial perfusion enables quantification of the
      haemodynamic consequences of LV systolic and diastolic dysfunctions in ischaemic
      cardiomyopathy and could be useful in the evaluation of the central circulation
      in heart failure.

PMID- 16640514
TI  - Forearm blood flow and oxygen consumption in patients with bilateral repetitive
      strain injury measured by near-infrared spectroscopy.
AB  - Despite the social impact of repetitive strain injury (RSI), little is known
      about its pathophysiological mechanism. The main objective of this study was to
      assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in
      individuals with RSI during isometric contractions of the forearm. We employed
      the non-invasive optical technique near-infrared spectroscopy to assess forearm
      VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their
      individual maximal voluntary strength. Twenty-two patients with RSI symptoms in
      both arms (bilateral RSI) and 30 healthy age-matched subjects participated in
      this cross-sectional study. The results showed lower mVO2 during exercise and a
      reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in
      the forearms of individuals with RSI compared with their controls at similar
      working intensities. This finding indicates that the underlying vasculature may
      be impaired. Although these findings contribute to the understanding of RSI,
      future research is necessary to further unravel the mechanisms of this area.

PMID- 16640515
TI  - Cardiac pumping capability in patients with peripheral vascular disease.
AB  - INTRODUCTION: Peripheral vascular disease (PVD) is a condition characterized by
      atherosclerotic occlusive disease of the lower extremities, low functional
      capacity and low exercise tolerance. Less empirical data are available concerning
      the cardiovascular response to maximum exercise tests in patients with PVD. The
      purpose of this study was to examine cardiovascular variables in patients with
      peripheral vascular disease. METHODS: Fifty patients (67 +/- 9 years) completed
      an incremental exercise test (2 min stages, 3.2 km h(-1), with increases of 2%
      every 2 min) to maximum claudication pain. Maximal oxygen consumption (VO2) was
      assessed on a breath-by-breath basis by online expiratory gas analysis (CardiO2,
      Medical Graphics Co.). Blood pressure was recorded at peak exercise. Following a
      30-min rest period, patients exercised at the highest level attained during the
      first test and cardiac output (QT) was measured using the exponential non
      invasive rebreathing method. Cardiac power output peak (CPOpeak) in Watts (W),
      was then computed. RESULTS: Mean +/- SD values were; 13.85 +/- 4.14 ml kg min(
      1); maximal walk time 357 +/- 227 s; peak mean arterial pressure 127 +/- 15 mmHg;
      9.8 +/- 2.39 (l min(-1)); CPO 2.86 +/- 0.87 W. CONCLUSION: Patients with
      peripheral vascular disease demonstrate attenuated levels of cardiovascular
      capacity. This group of patients should be given exercise therapy in order to
      improve cardiovascular status and ambulatory function.

PMID- 16640516
TI  - Test-retest reliability for two indices of ventilatory efficiency measured during
      cardiopulmonary exercise testing in healthy men and women.
AB  - The level of ventilation (VE)) at a given carbon dioxide output (CO2) determines
      ventilatory efficiency. During cardiopulmonary exercise testing (CPET),
      ventilatory efficiency can be measured as the slope of the (VE) versus VCO2
      relationship or the lowest VE/VCO2. We evaluated the test-retest reliability of
      these two ventilatory efficiency indices in 29 healthy subjects (14 males). Each
      subject performed duplicate cycle ergometer tests on different days. Ventilation
      and the gas fractions for oxygen and CO2 were measured with a Vacumed metabolic
      cart. Linear regression analysis of the VE versus VCO2 slope for the duplicate
      tests in the males, females, and both sexes combined yielded correlation
      coefficients of 0.822, 0.942, and 0.910, respectively. The corresponding
      correlation coefficients for the lowest VE/VCO2 were 0.745, 0.929, and 0.884. A
      comparison of the test-retest correlation coefficients between the two
      ventilatory efficiency measures for the men, women, and both sexes combined
      revealed that they were not significantly different and, for a given index, there
      were no sex differences. The bias (mean of difference scores between tests) and
      95% limits of agreement for the VE versus VCO2 slope in the males, females, and
      both sexes combined were -0.05 +/- 2.41, -0.57 +/- 1.92, and -0.32 +/- 2.20,
      respectively. The bias and 95% limits of agreement for the lowest VE/VCO2 were
      very similar with values of 0.06 +/- 2.45, -0.22 +/- 2.03, and -0.10 +/- 2.27. We
      conclude that the test-retest reliability for the VE versus VCO2 slope and the
      lowest VE/VCO2 is the same and that there is no sex difference in reliability for
      either index of ventilatory efficiency.

PMID- 16640517
TI  - Validation of a screening protocol for identifying low-risk candidates with type
      1 diabetes mellitus for kidney with or without pancreas transplantation.
AB  - BACKGROUND: Certain clinical risk factors are associated with significant
      coronary artery disease in kidney transplant candidates with diabetes mellitus.
      We sought to validate the use of a clinical algorithm in predicting post
      transplantation mortality in patients with type 1 diabetes. We also examined the
      prevalence of significant coronary lesions in high-risk transplant candidates.
      METHODS: All patients with type 1 diabetes evaluated between 1991 and 2001 for
      kidney with/without pancreas transplantation were classified as high-risk based
      on the presence of any of the following risk factors: age >or=45 yr, smoking
      history >or=5 pack years, diabetes duration >or=25 yr or any ST-T segment
      abnormalities on electrocardiogram. Remaining patients were considered low risk.
      All high-risk candidates were advised to undergo coronary angiography. The
      primary outcome of interest was all-cause mortality post-transplantation.
      RESULTS: Eighty-four high-risk and 42 low-risk patients were identified.
      Significant coronary artery stenosis was detected in 31 high-risk candidates.
      Mean arterial pressure was a significant predictor of coronary stenosis (odds
      ratio 1.68; 95% confidence interval 1.14-2.46), adjusted for age, sex and
      duration of diabetes. In 75 candidates who underwent transplantation with median
      follow-up of 47 months, the use of clinical risk factors predicted all eight
      deaths. No deaths occurred in low-risk patients. A significant mortality
      difference was noted between the two risk groups (p = 0.03). CONCLUSIONS: This
      clinical algorithm can identify patients with type 1 diabetes at risk for
      mortality after kidney with/without pancreas transplant. Patients without
      clinical risk factors can safely undergo transplantation without further cardiac
      evaluation.

PMID- 16640518
TI  - Accidental transplantation of a kidney with a cystic renal cell carcinoma
      following living donation: management and 1 yr follow-up.
AB  - Transmission of cancer is a fatal risk in organ transplantation. We present a
      case of incidental renal carcinoma in a kidney obtained from a living donor. A 56
      yr-old father was evaluated for donation for his 28-yr-old daughter. An MRT scan
      revealed two cysts in the right kidney. Right-sided donor nephrectomy and
      subsequent transplantation was performed. The wall of the prominent cyst was
      partially excised prior to transplantation. Histology revealed a high-grade renal
      clear cell carcinoma 10 d after transplantation. Following careful evaluation the
      recipient underwent partial nephrectomy. Immunosuppression was switched to
      rapamune. The graft function remained stable. Donor and recipient are without
      evidence of tumor recurrence 1 yr after transplantation. Our policy to obtain the
      kidney presenting anatomical variations proved to be beneficial for the donor. In
      case of transmission of cancer partial resection preserving graft function might
      be justified.

PMID- 16640519
TI  - A routine liver transplantation in a patient with situs inversus: a case report
      and an overview of the literature.
AB  - Liver transplantation (LT) in an adult with situs inversus (SI) is extremely rare
      and requires precise pre-operative management. A 48-yr-old male with SI suffering
      from alcoholic liver cirrhosis underwent LT at our institution in March 2003. Pre
      operatively, liver anatomy was determined by CT scan, three-dimensional liver
      reconstruction and angiography. LT was performed using the Belghiti technique
      with side-to-side cavo-caval anastomosis, transplanting a graft from a donor with
      normal anatomy. Post-operatively, the patient recovered without major
      complications, except an epileptic event because of a central pontine
      myelinolysis, and he was discharged on the 25th post-operative day. Three months
      after surgery, the T-drain placed intra-operatively into the donor bile duct was
      removed; transplant perfusion and function were stable with an actual follow-up
      period of 24 months. LT in patients with SI is feasible. Pre-operative imaging
      with three-dimensional reconstruction is a beneficial tool for operation planning
      in patients with rare anatomic variations.

PMID- 16640520
TI  - Heparin-induced thrombocytopenia following pancreatectomy and islet auto
      transplantation.
AB  - We report the case of a female with chronic pancreatitis who underwent multiple
      surgical procedures leading to total resection of the pancreas with successful
      islet auto-transplantation. Postoperatively, she developed heparin-induced
      thrombocytopenia. Heparinization prior to islet infusion is currently recommended
      to prevent portal vein thrombosis. Antibodies against heparin are not standard
      pre-operative testing for islet transplantation. Timely screening for heparin
      dependent anti-platelet antibody should be kept in consideration for elective
      surgical cases (especially following previous surgeries) including pancreatic
      islet allo- and auto-transplantation.

PMID- 16640521
TI  - Comparison of two different techniques of reperfusion in adult orthotopic liver
      transplantation.
AB  - The aim of this study was to determine the impact of two reperfusion techniques
      on the peri-operative hemodynamic changes and early post-operative graft function
      of adult patients undergoing orthotopic liver transplantation. MATERIAL AND
      METHODS: From June 2003 to May 2004, 50 consecutive liver transplants were
      performed and divided into two groups: group A, 25 patients, portal vein flush
      with 500 cm(3) of Ringer's lactate without vena caval venting. Group B, 25
      patients, vena caval venting with no portal vein flush. Donor and recipient
      characteristics were similar in both groups. Sixty-four different parameters were
      analyzed, and Pearson's chi(2) test and t-test were used for statistical
      analysis, p<or=0.05. RESULTS: One patient (4%) in group B experienced a post
      reperfusion syndrome (PRS). Pearson's chi(2) test found a significant
      relationship between the analyzed parameters and the two different reperfusion
      techniques for 10 parameters (t-test analysis showed a significant difference
      between the two groups in favor of group A). CONCLUSIONS: In our transplant
      center, portal vein flush without vena caval venting provided a lower incidence
      of hemodynamic changes in the peri-operative period after liver transplantation
      and earlier recovery of the graft function.

PMID- 16640522
TI  - Gender-related differences of renal mass supply and metabolic demand after living
      donor kidney transplantation.
AB  - Kidney donation from female donors to male recipients has been reported to be
      associated with decreased allograft survival. Whether there was a gender-related
      inadequacy between donor nephron supply and recipient functional demand was
      investigated in this study. One hundred ninety-five living donor kidney
      transplant recipients that had neither ischemic injury, episode of rejection, nor
      any complication were included. Weights and heights of both donors and recipients
      were recorded to calculate body surface area, lean body weight, and body mass
      index. The donated kidney was weighed just after cold flush, and the recipient's
      serum creatinine (Scr) was measured on a daily basis post-operatively. When the
      recipient's Scr reached the baseline, a 24-h urine was collected for the amount
      of proteinuria (Upr), creatinine excretion (Ucr) and creatinine clearance (Ccr)
      calculation. The effect of donor and recipient gender was analysed by independent
      sample t-test. On average, male donors and recipients were heavier and taller
      than females. However, the mass of kidneys donated from men and women were not
      statistically different. The gender-related differences in post-transplant Scr
      and Ucr of recipients were associated with the differences in the parameters of
      metabolic demands of recipients rather than with the weight of implanted kidney
      (renal mass supply) or with pre-operative renal functions of donors (functional
      supply). The early graft function is not determined by donor gender. The effect
      of recipient gender on the graft function depends on the metabolic demands, which
      are higher in male recipients.

PMID- 16640523
TI  - Prevalence, severity and correlates of alcohol use in adult renal transplant
      recipients.
AB  - BACKGROUND: Severe alcohol use is recognized as a major public health concern,
      even though light to moderate alcohol use might have beneficial effects on
      health. Alcohol use has been studied to some extent in solid organ transplant
      populations, yet evidence is lacking on alcohol use and its correlates in the
      renal transplant population. The aim of this study was therefore to determine the
      prevalence, severity and correlates of alcohol use in renal transplant
      recipients. METHODS: This cross-sectional study is a secondary analysis of the
      Supporting Medication Adherence in Renal Transplantation (SMART) study. Alcohol
      use was assessed by patient's self-report. At risk and binge drinkers were
      classified using World Health Organization criteria. The following correlates of
      alcohol use were explored: adherence with immunosuppression (Siegal
      questionnaire; electronic monitoring), smoking, coping style (UCL), depressive
      symptomatology (BDI) and busyness/routine in life style (ACQ Busyness Scale).
      RESULTS: Two hundred and eighty-four patients were included in this analysis,
      58.1% male, with a mean age of 54 yr (range 20-84) and a median of seven
      (interquartile ranges [IQR] 8) yr post-transplantation. A total of 52.8% of study
      participants reported to drink alcohol at least once a week. Two hundred and
      eighty of 284 subjects (98.5%) were drinking at low risk, four at moderate risk
      (1.5%). None of the participants were drinking severely. Correlates of alcohol
      use were male gender and being professionally active. CONCLUSION: Alcohol use is
      less prevalent in renal transplant recipients than in the general population.
      Severe alcohol use does not seem to represent a serious problem in renal
      transplant patients.

PMID- 16640524
TI  - Post-transplant lymphoproliferative disorders after lung transplantation: first
      line treatment with rituximab may induce complete remission.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are potentially
      lethal complications of solid organ transplantation. We, here, report on our
      experience with rituximab, an anti-CD20 monoclonal antibody, as first-line
      treatment for PTLD in six lung transplant recipients. PATIENTS AND METHODS: Two
      of the patients developed PTLD during the first year after transplantation, while
      four developed late-onset PTLD. One patient presented with PTLD localized to the
      graft, one had unilateral cervical lymph nodes, and the others presented with
      multi-organ involvement. All patients had diffuse large B-cell lymphoma.
      Immunosuppressive therapy was reduced and rituximab was administered at a dose of
      375 mg/m(2)/wk for 4 wk. RESULTS: One patient did not respond to the first two
      courses of rituximab, received conventional chemotherapy, and achieved complete
      remission; four patients achieved complete remission after four courses with a
      median relapse-free survival of 34 months (range: 14-55); and one patient did not
      respond and died. The diagnosis of complete remission was established by
      conventional imaging techniques combined to whole-body positron emission
      tomography scan. CONCLUSIONS: We conclude that reduction in immunosuppression
      combined to first-line treatment with rituximab may induce long-term complete
      remission in lung transplant recipients presenting PTLD.

PMID- 16640525
TI  - Limitation of the model for end-stage liver disease for outcome prediction in
      patients with cirrhosis-related complications.
AB  - The model for end-stage liver disease (MELD) has been used to prioritize
      cirrhotic patients awaiting liver transplantation. Bleeding esophageal varices,
      spontaneous bacterial peritonitis and hepatic encephalopathy are major
      complications of cirrhosis and traditional indications for liver transplantation
      evaluation. However, these complications are not included in the MELD and it is
      not clear if these complications correlate with MELD score in terms of outcome
      prediction. This study aimed to investigate the feasibility of cirrhosis-related
      complication as a prognostic predictor in 290 cirrhotic patients. The MELD score
      and outcome were compared between patients with and without cirrhosis-related
      complications. There was no significant difference of the MELD score between
      patients with (n = 67) and without (n = 223) complications (11.6 +/- 2.9 vs. 12.2
      +/- 3.2, p = 0.184). The area under the receiver operating characteristic curve
      was 0.687 for MELD vs. 0.604 for complications (p = 0.174) at six months, and the
      area was 0.641 for MELD vs. 0.611 for complications (p = 0.522) at 12 months. A
      high MELD score and presence of complications had a similar profile of predictive
      accuracy and both were significant predictors of mortality at six and 12 months
      in multivariate logistic regression analysis. Patients with cirrhosis-related
      complications at presentation had a decreased survival compared with those
      without complications (p < 0.0001). In conclusion, the occurrence of cirrhosis
      related complications is a predictor of poor prognosis. While early
      transplantation referral is recommended, these patients do not necessarily have a
      higher MELD score and could be down-staged in the MELD era.

PMID- 16640526
TI  - Association between insulin resistance and endothelial dysfunction in renal
      transplant recipients.
AB  - BACKGROUND: Endothelial dysfunction is a common finding in renal transplant
      recipients (RTR) and is related to impaired local regulation of vasodilative and
      vasoconstrictive substances, such as nitric monoxide (NO) and endothelin-1 (ET
      1). In non-transplanted patients, an association between impaired endothelial
      function and insulin resistance has been shown. Whether such an association also
      exists in RTR is unknown. OBJECTIVE: The aim of the present study was to examine
      whether insulin resistance is associated with endothelial dysfunction in RTR.
      MATERIAL AND METHODS: A total of 47 RTR in a stable phase six yr post-transplant
      were included in the statistical analysis. The immunosuppressive therapy was
      based on cyclosporine and prednisolone. Non-invasive assessment of endothelial
      function was performed with laser Doppler flowmetry of the forearm skin
      vasculature after local acetylcholine stimulation. Oral glucose tolerance tests
      comprising both glucose and insulin measurements were used to calculate insulin
      sensitivity (IS) indices. NO, ET-1 and von Willebrand factor were measured in
      fasting plasma samples. RESULTS: Normal glucose tolerance was found in 31 RTR. In
      these subjects, both IS (r(2) = 0.164, p = 0.044) and plasma NO (r(2) = 0.326, p
      = 0.002) were significantly correlated with endothelial function. Patients with
      glucose intolerance (n = 16) had higher plasma ET-1 and lower NO levels, but the
      association between IS and endothelial function was not significant in these
      subjects. In the total patient cohort, IS and endothelial function tended to be
      correlated (p = 0.127). CONCLUSIONS: Endothelial dysfunction is significantly
      associated with insulin resistance in normoglycemic RTR but explains a rather
      small part of the variation. In glucose-intolerant recipients, IS appears to be
      more critically dependent on other factors not revealed in the present study.

PMID- 16640527
TI  - Prediction of glomerular filtration rate in renal transplant recipients: cystatin
      C or modification of diet in renal disease equation?
AB  - BACKGROUND: To overcome disadvantages of serum creatinine two strategies have
      been suggested to identify patients with reduced glomerular filtration rate
      (GFR). On the one hand, the Modification of Diet in Renal Disease (MDRD) equation
      is now recommended to classify the stage of chronic kidney disease. On the other
      hand, cystatin C (Cys C) has been investigated in numerous studies, finding a
      higher sensitivity than creatinine in detecting diminished GFR. To date, no
      comparison of both strategies in patients after renal transplantation has been
      performed. METHODS: One hundred and five consecutive renal transplant recipients
      underwent (99m)Tc-DTPA-- clearance measurement. Simultaneously, MDRD estimates
      were calculated and Cys C serum levels were determined. ROC analyses were
      performed at different decision points from 20 to 70 mL/min/1.73 m(2). RESULTS:
      Although the area under the curve did not differ significantly between MDRD and
      Cys C within the tested GFR range, the AUC for Cys C tended to be higher when GFR
      exceeded 55 mL/min/1.73 m(2). A significantly higher diagnostic accuracy for Cys
      C compared with MDRD (p = 0.045 at 65 mL/min/1.73 m(2)) was found when
      investigating the subgroup of patients with well-functioning grafts (GFR>40
      mL/min/1.73 m(2)). CONCLUSION: MDRD equation is equivalent to Cys C measurement
      in renal transplant recipients. As availability of MDRD is superior to Cys C, we
      recommend GFR estimation using the MDRD equation. Nevertheless, Cys C may serve
      as a confirmation test of high MDRD estimates in patients with well-functioning
      grafts because of superior accuracy in these patients.

PMID- 16640528
TI  - Hepatitis B prophylaxis post-liver transplant without maintenance hepatitis B
      immunoglobulin therapy.
AB  - BACKGROUND: We examined outcomes in recipients who underwent a liver transplant
      for HBV-induced liver disease and received a protocol for prophylaxis that did
      not use HBIG maintenance. RESULTS: Between October 2002 and July 2005, a total of
      14 liver transplant recipients were identified that met the study criteria. Mean
      recipient age was 47.6 yr; mean donor age was 37.2 yr. Category of transplant was
      as follows: cadaveric liver (n = 10, 71%), cadaveric split-liver (n = 2, 14%),
      and cadaveric liver-kidney (n = 2, 14%). Liver disease was diagnosed at a mean of
      7.3 yr before transplant; three (21%) had a coexisting hepatocellular cancer at
      the time of transplant. Pre-transplant, all 14 (100%) recipients were hepatitis B
      surface antigen (HBsAg) positive, and 11 (79%) were HBV DNA positive (mean viral
      load of 251.2 pg/mL). Three (21%) were E antigen positive, and one (7%) was D
      antigen positive. Pre-transplant, seven patients (50%) were on anti-viral therapy
      and there was documented diminution in viral loads after initiating anti-viral
      therapy in 3 cases. Three (21%) were hepatitis C virus (HCV) antigen positive and
      all had low-RNA titers. With mean follow-up of 14.1 months, all 14 patients are
      alive with a functioning graft. Mean ALT, AST and total bilirubin values are
      currently at 43.2, 32.2, and 0.84, respectively. One recipient remains HBsAg
      surface antigen positive post-transplant but has normal lab values. The remaining
      recipients have no evidence of HBV recurrence by serology and protocol biopsies.
      The regimen has been well tolerated without the need for drug reduction or
      discontinuation because of side-effects. CONCLUSION: Longer follow-up is needed,
      but this regimen may represent an alternative to chronic HBIG maintenance
      therapy.

PMID- 16640529
TI  - Long-term follow-up after recurrence of primary biliary cirrhosis after liver
      transplantation in 100 patients.
AB  - Orthotopic liver transplantation (OLT) is the only effective curative therapy for
      end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent,
      although recent data have shown a recurrence rate of PBC of up to 32% after
      transplantation. The aim of this study is to investigate the course after disease
      recurrence, particularly with regard to liver function and survival in a long
      term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations
      were performed in 1,415 patients at the Charite, Virchow Clinic. Protocol liver
      biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%)
      patients suffered from histologically proven PBC. Primary immunosuppression
      consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately
      after OLT, all patients received ursodeoxycholic acid. Corticosteroids were
      withdrawn three to six months after OLT. The median age of the 85 women and 15
      men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation
      was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79
      months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82%
      respectively. Ten patients (10%) died after a median survival time of 32 months.
      Two of these patients developed organ dysfunction owing to recurrence of PBC.
      Histological recurrence was found in 14 patients (14%) after a median time of 61
      months (range 36-122 months). Patients with Tac immunosuppression developed PBC
      recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven
      patients developed an acute rejection and two patients a chronic rejection
      episode. Liver function did not alter within the first five yr after
      histologically proven PBC recurrence. Multivariate analysis of the investigated
      patients showed that the recipient's age and Tac immunosuppression were
      significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr
      after liver transplantation, owing to PBC, in addition to maintenance of liver
      function, shows excellent organ and patient survival rates. Although protocol
      liver biopsies revealed histological recurrence in 14 (14%) patients, only two
      patients developed graft dysfunction. Tac-treated patients showed more frequently
      and also earlier histologically proven PBC recurrence; however, in our population
      we could not observe an impact on graft dysfunction and patient's survival.

PMID- 16640530
TI  - Monitoring of cyclosporine levels in transplant recipients using self
      administered fingerprick sampling.
AB  - Use of C(2) monitoring for cyclosporine A (CsA) microemulsion results in improved
      clinical outcomes vs. trough (C(0)) monitoring. Logistical issues include
      accurate timing of the C(2) sample; requirement for sample dilution with most
      standard assay techniques; and inconvenience for patients. Recently, it has been
      shown that CsA concentrations in capillary blood correlate closely with levels in
      venepuncture samples, and that liquid chromatography tandem mass spectrometry (LC
      MS/MS) can analyse CsA concentration using undiluted capillary blood from
      fingerprick samples. In a study to assess the feasibility of CsA monitoring, 52
      stable heart transplant patients were provided with kits to take fingerprick
      trough and C(2) blood samples at home, returning them to the laboratory by post
      for LC-MS/MS analysis. In total, 225 samples were provided, of which 14 (6%) were
      unsuitable for analysis because of clotting (n = 10) or insufficient volume (n =
      4). Discomfort was not a problem and initial difficulties that some patients
      reported in taking the samples resolved with experience. All samples were
      returned by the postal system in a timely manner. Use of fingerprick assays could
      allow transplant physicians to have access to C(2) levels when patients visit the
      clinic for review, and avoids the need for patients to attend the clinic or local
      healthcare centre solely for venepuncture. A barrier to more widespread
      introduction of fingerprick testing is likely to be lack of suitable MS
      facilities and trained personnel. In conclusion, self-administered fingerprick
      testing for CsA blood levels is practical to implement and highly convenient for
      patients and offers advantages for the transplant team.

PMID- 16640531
TI  - Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker
      for graft outcomes in a predominantly African-American renal transplant cohort.
AB  - The HLAMatchmaker program is based on the donor/recipient comparison of the
      polymorphic triplet amino-acid sequences of the antibody-accessible regions on
      the human leucocyte antigen (HLA) molecule. The previous reports on its
      predictive value for renal allograft outcomes are conflicting. We conducted a
      retrospective study in a predominantly African-American (AA) cohort (N = 101, 94%
      AA). HLA typing was performed by molecular methods and triplet matching using
      HLAMatchmaker. Study end points included graft survival and incidence of acute
      rejection. The relationship between the number of triplet mismatches (TMM) and
      the degree of HLA antigen MM was evaluated using Pearson's correlation
      coefficient. Logistic regression models were used to examine the association
      between triplet matching and the study end points. Kaplan-Meier and Cox
      proportional hazard models were used for graft survival analysis. The strongest
      relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ
      (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw
      HLA loci and the study end points was not statistically significant. However,
      after grouping, the unadjusted estimates of graft survival for those with more
      than 10 Class I TMM were significantly worse than the others (p = 0.03).
      Adjusting for the effect of donor source, recipient characteristics and the
      immunosuppressive regimen did not change this association (hazard ratio = 0.2,
      confidence interval = 0.04-1.1). We conclude that triplet matching using
      HLAMatchmaker can provide useful prognostic information in kidney transplantation
      and that more than 10 donor/recipient Class I HLA TMM is predictive of worse
      graft outcome.

PMID- 16640532
TI  - Extent of hepatectomy on splenic hypertrophy and platelet count in live liver
      donors.
AB  - The extent of donor hepatectomy may affect splenic hypertrophy and platelet
      count. The subjects were 50 live liver donors. The ratio of the graft weight to
      total liver volume (GW/TLV) and the splenic hypertrophy ratio, expressed as the
      splenic volume one month after surgery divided by that before surgery, were
      calculated. The platelet count one month after surgery was divided by that before
      surgery to determine the rate of the platelet count decrease. The correlation of
      GW/TLV to the splenic hypertrophy ratio and the rate of the platelet count
      decrease were examined. The median (range) GW/TLV was 54 (28-71)%. The splenic
      hypertrophy ratio and the rate of the platelet count decrease was 133 (99-191)%
      and 92 (71-129)%, respectively. GW/TLV positively correlated with the splenic
      hypertrophy ratio (Spearman's correlation coefficient (r(s)) = 0.448, p = 0.001),
      and negatively correlated with the rate of the platelet count decrease (r(s) = 
      0.471, p < 0.001). Multivariate analysis revealed that GW/TLV influenced the
      splenic hypertrophy ratio [adjusted odds ratio (OR), 12.0; 95% confidence
      interval (CI), 1.32-9.04; p = 0.01] and the ratio of the platelet count decrease
      (adjusted OR, 11.6; 95% CI, 1.40-8.33; p = 0.01). Larger graft procurement might
      place living liver donors at higher risk for post-operative thrombocytopenia.

PMID- 16640533
TI  - Initial experience with bosentan therapy in patients considered ineligible for
      heart transplantation because of severe pulmonary hypertension.
AB  - BACKGROUND: Pre-operative elevated pulmonary vascular resistance (PVR) has been
      associated with increased right ventricular failure and mortality after heart
      transplantation. The aim of this study was to assess the efficacy of bosentan, an
      oral endothelin-receptor antagonist, to reduce PVR in patients considered
      ineligible for heart transplantation because of severe pulmonary hypertension.
      METHODS: Seven patients with end-stage congestive heart failure and considered
      ineligible for heart transplantation because of severe pulmonary hypertension
      (PVR>2.5 Wood units after nitroprusside infusion) were included in the study.
      They received bosentan 62.5 mg b.i.d. for four wk and 125 mg b.i.d. thereafter.
      Right heart catheterization was repeated after six wk of therapy. RESULTS: After
      six wk of bosentan therapy, there was a significant decrease in PVR (6.0 +/- 2
      vs. 3.8 +/- 2 Wood units, before vs. after bosentan; p = 0.02), in PVR during
      nitroprusside infusion (3.3 +/- 1 vs. 2.1 +/- 1 Wood units, before vs. after
      bosentan; p = 0.02) and in diastolic pulmonary artery pressure (33 +/- 7 vs. 23
      +/- 7 mmHg, before vs. after bosentan; p = 0.04). No significant adverse events
      were observed. After bosentan therapy, five patients had PVR<or=2.5 Wood units.
      They were included in the waiting list and all five had a successful heart
      transplantation, although two of them required bosentan after surgery.
      CONCLUSIONS: In patients considered ineligible for heart transplantation because
      of high PVR, bosentan therapy significantly reduced PVR. These data suggest that
      therapy with endothelin-receptor blockers might be useful to identify a subgroup
      of patients with high PVR who can benefit from heart transplantation.

PMID- 16640534
TI  - The association between length of post-kidney transplant hospitalization and long
      term graft and recipient survival.
AB  - BACKGROUND: There has been a general trend towards shortened length of post
      kidney transplant hospitalization (LOH). The decision regarding patients's
      discharge from the hospital theoretically may be based on several factors,
      including, but not limited to, patient well being, insurance status, family
      situation and other, mostly socio-economic factors, as opposed to hard medical
      evidence. However, the appropriate LOH in kidney transplant recipients is not
      well studied regarding long-term outcomes. METHODS: This study retrospectively
      analysed the association between LOH and graft and recipient survival based on
      United States Renal Data System dataset. In total, 100,762 patients who underwent
      transplant during 1995-2002 were included. Kaplan-Meier survival analysis and Cox
      models were applied to the whole patient cohort and on sub-groups stratified by
      the presence of delayed graft function, patient comorbidity index and donor type
      (deceased or living). RESULTS: In recipient survival, both short (<4 d) and long
      (>5 d) LOH showed a significant adverse effect (p < 0.01) on survival times. In
      the analysis of graft survival, long LOH (>or=2 wk) also showed significant
      adverse effects (p < 0.001) on survival times. However, short LOH (<4 d) did not
      reach statistical significance, although it was still associated with adverse
      effects on graft survival. These observations were consistent across the whole
      patient cohort and sub-groups stratified by the presence of delayed graft
      function, patient comorbidity index and donor type. CONCLUSION: Clinical
      considerations should be used to make the decision regarding appropriate time of
      post-kidney transplant recipient discharge. Based on this study, shorter than
      four d post-kidney transplant hospitalization may potentially be harmful to long
      term graft and recipient survival.

PMID- 16640535
TI  - Pancreas transplantation: advantages of both enteric and bladder drainage
      combined in a two-step approach.
AB  - BACKGROUND: Although there is a tendency to perform enteric drainage of pancreas
      transplants in simultaneous pancreas-kidney (SPK) transplantation, bladder
      drainage is still preferable in pancreas transplantation alone (PTA) or after a
      previous kidney transplantation (PAK). Our hypothesis was that enteric conversion
      of a bladder drained pancreas is an effective and safe procedure. We studied the
      complication rate and physiological effects of enteric conversion in patients
      with primary bladder-drained SPK transplantation. PATIENTS: We performed 51
      enteric conversions in bladder-drained SPK transplant recipients. As we observed
      a low complication rate, with time enteric conversions were also performed for
      less strict and severe indications. RESULTS: The main indications for conversion
      were urological problems, metabolic complications and reflux-pancreatitis. The
      median transplantation-conversion interval was 12 months (range 2-40 months).
      Post-operative complications consisted of seven urinary tract infections, two low
      grade superficial wound infections, one minor bleeding, one phlebitis and one
      paralytic ileus. In two patients, a relaparotomy was necessary. No graft
      rejection following enteric conversion was found. Long-term renal and pancreatic
      function were not affected by the enteric conversion. Three-year patient, kidney
      and pancreas survival rates after enteric conversion were 93, 97 and 93%,
      respectively (censored data). CONCLUSION: Enteric conversion after pancreas
      transplantation is an effective and safe procedure. Therefore, we suggest a
      policy of a two-step approach of primary bladder drainage followed by an enteric
      conversion of the pancreas in a selected group of SPK patients.

PMID- 16640536
TI  - Overcoming diabetic gastroparesis en route to kidney transplant.
AB  - Gastroparesis is a debilitating condition that affects a significant number of
      diabetic patients. Some of these patients have end-stage renal disease and are in
      need of kidney transplant. Symptoms of gastroparesis include: early satiety,
      pyrosis, epigastric pain, nausea and vomiting, which may lead to caloric and
      electrolyte deficiencies as well as significant weight loss. A viable option for
      diabetic gastroparesis patients who fail first line treatments consisting of
      dietary changes and gastric prokinetic medications is gastric electrical
      stimulator (GES) implantation. We present a 41-yr-old man and 35-yr-old woman
      with diabetic gastroparesis, who were initially deemed unacceptable candidates
      for renal transplantation because of marked malnourishment and a concern that
      they would not be able to tolerate immunosuppressant medications. In less than
      two yr following GES implantation, each patient underwent a successful kidney
      transplant.

PMID- 16640537
TI  - A case of fulminant post-transplant lymphoproliferative disorder and septicemia.
AB  - The fulminant form of post-transplant lymphoproliferative disorder (PTLD) is very
      uncommon and occurs in approximately 1% of PTLD patients. Approximately 85% of
      these lesions are of B-cell origin, and most of them are associated with Epstein
      Barr virus infection. Fulminant PTLD is frequently associated with a systemic
      inflammatory response syndrome, and may be difficult to differentiate from
      septicemia. We describe the case of a 59-yr-old man who suffered from prolonged
      septicemia in the immediate post-transplant period, and presented again four
      months after cardiac transplantation with fever, painful liver edge and
      gastrointestinal bleeding. The diagnosis of fulminant PTLD with advanced
      multiorgan infiltration by a diffuse large-cell lymphoma of B-cell phenotype was
      made. During treatment with rituximab, the patient died from Enterococcus faecium
      septicemia. The sequence of septicemia, PTLD and, finally again, septicemia is an
      unusual challenge and urges for an aggressive diagnostic approach, where markers
      like procalcitonin may aid in the discrimination of fulminant PTLD from
      septicemia.

PMID- 16640538
TI  - ABO-incompatible deceased donor liver transplantation with the use of antigen
      specific immunoadsorption and anti-CD20 monoclonal antibody.
AB  - In patients with fulminant liver failure requiring emergency liver
      transplantation, the only donor organ that becomes available may be ABO
      incompatible. The risk of graft failure because of antibody-mediated acute
      rejection is high, but can be reduced by various means. We reported a deceased
      donor ABO-incompatible liver allograft recipient who was treated with antigen
      specific immunoadsorption in combination with anti-CD20 monoclonal antibody and
      conventional plasmapheresis and immunosuppression. The patient was a 33-yr-old
      male with blood group A who presented with subacute liver failure of unknown
      aetiology and received a blood group AB liver graft. Pretransplant he underwent
      plasmapheresis and received one dose of rituximab. The immunosuppressive regimen
      consisted of methylprednisolone, tacrolimus and mycophenolate mofetil. Despite
      regular post-operative plasmapheresis sessions, anti-B antibody titres increased.
      Antigen-specific immunoadsorption with depletion of anti-B antibodies was
      performed from day nine to day 17. Thereafter, anti-B IgM and IgG antibody titres
      remained low. After one month the patient was reoperated with hepaticojejunostomy
      because of bile duct necrosis and with reconstruction of a stenotic hepatic
      artery. A mild rejection was successfully treated with methylprednisolone four
      months post-transplant. At six months post-transplant there was a stricture of
      the biliary-enteric anastomosis, but the graft was well functioning. We conclude
      that antigen-specific immunoadsorption can be an important adjuvant therapy to
      control recipient anti-A/B antibody levels and prevent acute rejection in ABO
      incompatible deceased donor liver transplantation.

PMID- 16640539
TI  - The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma
      patients.
AB  - BACKGROUND: A new approach to prevent disease recurrence in high-risk melanoma
      patients involves immunization with gp100 and tyrosinase peptides. This is the
      first study to examine the effects of such treatments on nevi. DESIGN: We studied
      biopsies of 'clinically atypical' nevi from 10 patients before and after peptide
      vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth,
      satellite metastases, or at least one positive lymph node. We performed
      immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART
      1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). RESULTS: Immunohistochemistry
      showed no differences in staining due to vaccination in either the immunologic or
      melanocytic markers. However, there was a significant increase in both p53 and
      bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post
      treatment. DISCUSSION: The primary goal of peptide vaccinations with gp100 and
      tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma
      recurrence. Nevi were studied in order to assess the effects on benign
      melanocytes. No significant changes in lymphocytes, langerhans cells, expression
      of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2
      raises the possibility that vaccination with melanocytic antigens stimulates a
      response in benign melanocytes.

PMID- 16640540
TI  - Clear cell atypical fibroxanthoma - report of a case with review of the
      literature.
AB  - Clear cell atypical fibroxanthoma (CCAFX) is a rare variant of atypical
      fibroxanthoma (AFX), a pleomorphic dermal tumour associated with a good
      prognosis. A 67-year-old man presented with a rapidly growing nodule on the ear,
      which had appeared over a 2-week period. Sections showed an ulcerated nodule
      composed of pleomorphic spindled and polygonal cells with clear cytoplasm,
      invested by a delicate vascular stroma, reminiscent of clear cell renal cell
      carcinoma. Numerous mitotic figures were seen. The tumour cells stained with
      vimentin, CD68 and CD99 and were cytokeratin-negative. The immunohistochemical
      and ultrastructural features supported a diagnosis of CCAFX. The diagnosis of
      CCAFX requires the exclusion of other pleomorphic clear cell tumours that can
      occur in the skin by using a combination of morphology, immunohistochemistry and
      electronmicroscopy. Murali R, Palfreeman S. Clear cell atypical fibroxanthoma -
      report of a case with review of the literature.

PMID- 16640541
TI  - Multinucleate cell angiohistiocytoma. Report of five cases.
AB  - BACKGROUND: Multinucleate cell angiohistiocytoma is an infrequent and most likely
      non-neoplastic disorder usually seen in acral regions in elderly women. It
      presents clinically as asymptomatic red-to-brown tumors, with a tendency to
      confluence. It must be distinguished from other diverse cutaneous lesions,
      notably dermatofibroma, Kaposi sarcoma, and angiofibroma. METHODS: We report the
      clinical, histopathological, and immunohistochemical findings of five patients,
      all women aged between 51 and 78 years. All except the first presented lesions on
      both of the lower limbs. None of the patients developed spontaneous resolution of
      the lesions and one was successfully treated by cryosurgery. COMMENTS:
      Multinucleate cells are characteristic, but neither exclusive nor pathognomonic,
      of multinucleate cell angiohistiocytoma, since they can also appear in other
      inflammatory, neoplastic, or reactive processes. The presence of these cells and
      vascular proliferation in dermis media are the principal histopathological
      findings in this infrequent entity. In immunohistochemical studies, the
      multinucleate cells are often positive for vimentin and factor XIIIa.

PMID- 16640542
TI  - Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and
      dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa.
AB  - BACKGROUND: Distinction between cellular fibrous histiocytomas (FHs) with a deep
      component and dermatofibrosarcoma protuberans (DFSPs) can pose diagnostic
      problems. While CD68, CD34, and Factor XIIIa are helpful in distinguishing
      between these entities, none are diagnostically absolute. Recent work with CD163,
      a hemoglobin scavenger receptor, has demonstrated that this marker has high
      specificity for monocytes, macrophages, and histiocytes. Our goal is to evaluate
      the utility of CD163 in the diagnosis of dermatofibromas (DFs), cellular FHs, and
      DFSPs. METHODS: Sixty cases including 19 DFs, 23 cellular FHs with a deep
      component, and 18 DFSPs were tested with antibodies against CD163, CD68, CD34,
      and Factor XIIIa. RESULTS: CD163 was expressed in 17/19 (89%) DFs, 23/23 (100%)
      cellular FHs, and 3/18 (17%) DFSPs. CD68 was positive in 8/19 (42%) DFs, 19/23
      (83%) cellular FHs, and 1/16 (6%) DFSPs. CD34 was expressed in 1/19 (5%) DFs,
      5/23 (22%) cellular FHs, and 100% of DFSPs. Factor XIIIa labeled 4/19 (21%) DFs,
      11/23 (48%) cellular FHs, and 0/17 cases of DFSPs. CONCLUSIONS: CD163 expression
      is helpful in distinguishing between cellular FHs and DFSPs and will be useful in
      a panel of antibodies when these entities are in the differential diagnosis.
      Sachdev R, Sundram U. Expression of CD163 in dermatofibroma, cellular fibrous
      histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34,
      and Factor XIIIa.

PMID- 16640543
TI  - Pleomorphic hyalinizing angiectatic tumor of soft parts: case report and
      literature review.
AB  - Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a rare soft
      tissue neoplasm. Few cases have been reported in the literature thus far. PHAT is
      a spindle cell neoplasm with a prominent vascular component which displays some
      features of both neurilemoma and malignant fibrous histiocytoma. Lesions
      typically occur on the lower extremities of adults, however, lesions in other
      anatomic locations have been described. In this paper, we report a 60 years old
      female with PHAT of the right foot and review the current literature. El-Tal A-E
      K, Mehregan D. Pleomorphic hyalinizing angiectatic tumor of soft parts: case
      report and literature review.

PMID- 16640544
TI  - An unusual hamartoma of the folliculosebaceous-apocrine unit: a case report.
AB  - Hamartoma is a neoplasm-like lesion composed of an abnormal mixture of tissues
      native to the area. We report on an unusual example of a hamartomatous lesion
      that showed an abnormal mixture of elements of the folliculosebaceous-apocrine
      unit and arrector pili muscle. A 13-year-old female presented with two nodules
      situated 2 cm apart on the lower leg that were present since birth. The patient
      reported some enlargement and slight pain of the otherwise asymptomatic lesions
      during 2 years, before they were surgically removed. The patient obviously had no
      skin problems afterwards; her 12-year follow-up was significant for leucopenia
      and nephrolithiasis. The biopsies from both lesions looked identical. Each lesion
      was biphasic, i.e. composed of a predominant mesenchymal component and epithelial
      elements. The mesenchymal part resembled a leiomyoma, or in minor areas, the
      constituting cells had a myofibroblastic appearance. Encased within the
      mesenchymal component were large infundibulocystic structures and plentiful
      grouped and scattered roundish solid epithelial nodules, duct-like, glandular,
      and tubular elements. Some of the epithelial structures were reminiscent of those
      seen in tubular apocrine adenoma; others resembled syringomatous elements. We
      interpreted this unusual lesion as a hamartoma of the folliculosebaceous-apocrine
      unit.

PMID- 16640545
TI  - Ectopic hamartomatous thymoma: a case report with immunohistochemical study and
      review of the literature.
AB  - Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of
      EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19
      year-old man. The tumor consisted of spindle cells, epithelial cells, adipose
      cells, and a small amount of lymphocytes, as described previously.
      Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle
      actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes
      were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5%
      of cells were positive for MIB-1 and no cells stained for p53 and bcl-2.
      Recognition of EHT is important and needs to be differentiated from high-grade
      sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath
      tumor.

PMID- 16640546
TI  - Verruciform xanthoma-like phenomenon in seborrheic keratosis.
AB  - Verruciform xanthoma is xanthomatous dermal infiltrate in a proliferating
      epidermal lesion and is an uncommon phenomenon. It has been reported in various
      neoplastic or inflammatory conditions. We report a 72-year-old man who had an
      asymptomatic 1-cm black nodule on his abdomen. Histopathology showed a typical
      acanthotic type of seborrheic keratosis characterized by basaloid keratinocyte
      proliferation and pseudohorn cysts. Many aggregated xanthomatized cells were seen
      in dermal papillae within the acanthotic epithelium. Papillomatosis,
      parakeratosis, and neutrophil infiltrates, the histologic features of typical
      verruciform xanthoma, were not seen. The foamy cells were positive for CD-68 and
      vimentin and negative for cytokeratin and S-100. No human papillomavirus DNA was
      found by nested polymerase chain reaction. The blood lipid profile was normal.
      The presence of verruciform xanthomatous change in seborrheic keratosis provides
      further evidence that verruciform xanthoma may be a reactive phenomenon occurring
      in common skin disorders.

PMID- 16640547
TI  - Dermal nodular fasciitis: three case reports of the head and neck and literature
      review.
AB  - Nodular fasciitis is a benign reactive myofibroblastic proliferative process of
      unknown etiology. It presents as a solitary painless, rapidly growing nodule over
      several weeks' duration. The condition is self-limited, and proper diagnosis is
      essential to avoid unnecessary aggressive treatment. Diagnosis is often a
      challenge because it may be confused with a malignant tumor due to its aggressive
      clinical behavior and histological features. Immunohistochemical staining can be
      a useful tool to aid in the diagnosis. Although most commonly located on the
      extremities and then the trunk, it is estimated that the head and neck region
      represents only 10 to 20%. The majority of cases arise in the soft tissue, i.e.
      fascia, muscle, or subcutaneous tissue. Interestingly, cases in the head and neck
      region often involve dermal tissue. There have been five separate reports
      documenting rare cases of dermal nodular fasciitis in the dermatopathology
      literature and one case series involving 28 of 50 dermal variants from the
      external ear region. We report three additional cases of dermal nodular fasciitis
      occurring on the left cheek, base of the scalp, and right medial canthus.

PMID- 16640548
TI  - Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome
      and metastases following pregnancy.
AB  - BACKGROUND: The most frequent molecular abnormality observed in
      dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring
      chromosome or translocation resulting in fusion of the gene encoding the alpha
      chain of type 1 collagen, COL1A1 from 17q22, to the platelet-derived growth
      factor beta-chain, PDGFB gene from 22q13. Rare cases documenting variant ring or
      marker chromosomes involving regions other than 17q22 and 22q13 have been
      reported. Further analysis in three of these cases demonstrated the presence of
      the COL1A1 and PDGFB genes. METHODS: We report a further case of DFSP with a rare
      variant ring chromosome. The tumor appeared to undergo accelerated growth during
      pregnancy, then metastasized following pregnancy. We describe the clinical,
      histological, immunohistochemical, and cytogenetic features. RESULTS: The
      metastatic tumor showed a variant r(17;?) chromosome. A locus-specific probe was
      required to demonstrate presence of the PDGFB gene within the ring, indicating
      cryptic molecular rearrangement between chromosomes 17 and 22, and recombination
      with an unknown chromosome. CONCLUSIONS: Cryptic rearrangement of chromosomes 17
      and 22 should be suspected in variant ring chromosomes and translocations.
      Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical
      resection should be avoided.

PMID- 16640549
TI  - Lipomatous mixed tumor with follicular differentiation of the skin.
AB  - A very rare case of cutaneous mixed tumor with numerous adipose tissue and hair
      follicular structures in a 67-year-old Japanese male was reported. A well
      circumscribed tumor was in the subcutaneous tissue of the cheek and far from the
      parotid gland. Histologically, the tumor consisted of an admixture of the adipose
      tissue, fibromyxoid tissue with spindle cells, and branching tubular structures.
      Outer layers of ductal epithelial cells and single spindle cells were often in a
      transition, likely as typical mixed tumor. Branching ducts connected with
      keratinous cysts, strands of trichoblastic basophilic cells and clear cell nests.
      There was a gradual transition, between small-sized adipocytes and vacuolated
      spindle cells. No chondroid stroma was seen. To our knowledge, this tumor is the
      first case of a lipomatous mixed tumor with hair follicular differentiation. The
      case indicates an additional wide spectrum of histologic appearances of cutaneous
      mixed tumor.

PMID- 16640550
TI  - The importance of mitotic rate as a prognostic factor for localized primary
      cutaneous melanoma.

PMID- 16640552
TI  - Metallothioneins are multipurpose neuroprotectants during brain pathology.
AB  - Metallothioneins (MTs) constitute a family of cysteine-rich metalloproteins
      involved in cytoprotection during pathology. In mammals there are four isoforms
      (MT-I - IV), of which MT-I and -II (MT-I + II) are the best characterized MT
      proteins in the brain. Accumulating studies have demonstrated MT-I + II as
      multipurpose factors important for host defense responses, immunoregulation, cell
      survival and brain repair. This review will focus on expression and roles of MT-I
      + II in the disordered brain. Initially, studies of genetically modified mice
      with MT-I + II deficiency or endogenous MT-I overexpression demonstrated the
      importance of MT-I + II for coping with brain pathology. In addition, exogenous
      MT-I or MT-II injected intraperitoneally is able to promote similar effects as
      those of endogenous MT-I + II, which indicates that MT-I + II have both extra-
      and intracellular actions. In injured brain, MT-I + II inhibit macrophages, T
      lymphocytes and their formation of interleukins, tumor necrosis factor-alpha,
      matrix metalloproteinases, and reactive oxygen species. In addition, MT-I + II
      enhance cell cycle progression, mitosis and cell survival, while neuronal
      apoptosis is inhibited. The precise mechanisms downstream of MT-I + II have not
      been fully established, but convincing data show that MT-I + II are essential for
      coping with neuropathology and for brain recovery. As MT-I and/or MT-II compounds
      are well tolerated, they may provide a potential therapy for a range of brain
      disorders.

PMID- 16640553
TI  - Biology of mast cell tryptase. An inflammatory mediator.
AB  - In 1960, a trypsin-like activity was found in mast cells [Glenner GG & Cohen LA
      (1960) Nature 185, 846-847] and this activity is now commonly referred to as
      'tryptase'. Over the years, much knowledge about mast cell tryptase has been
      gathered, and a recent (18 January 2006) PubMed search for the keywords 'tryptase
      + mast cell*' retrieved 1661 articles. However, still very little is known about
      its true biological function. For example, the true physiological substrate(s)
      for mast cell tryptase has not been identified, and the potential role of
      tryptase in mast cell-related disease is not understood. Mast cell tryptase has
      several unique features, with perhaps the most remarkable being its organization
      into a tetrameric state with all of the active sites oriented towards a narrow
      central pore and its consequent complete resistance towards endogenous
      macromolecular protease inhibitors. Much effort has been invested to elucidate
      these properties of tryptase. In this review we summarize the current knowledge
      of mast cell tryptase, including novel insights into its possible biological
      functions and mechanisms of regulation.

PMID- 16640554
TI  - Intermonomer cross-linking of F-actin alters the dynamics of its interaction with
      H-meromyosin in the weak-binding state.
AB  - Previous cross-linking studies [Kim E, Bobkova E, Hegyi G, Muhlrad A & Reisler E
      (2002) Biochemistry 41, 86-93] have shown that site-specific cross-linking among
      F-actin monomers inhibits the motion and force generation of actomyosin. However,
      it does not change the steady-state ATPase parameters of actomyosin. These
      apparently contradictory findings have been attributed to the uncoupling of force
      generation from other processes of actomyosin interaction as a consequence of
      reduced flexibility at the interface between actin subdomains-1 and -2. In this
      study, we use EPR spectroscopy to investigate the effects of cross-linking
      constituent monomers upon the molecular dynamics of the F-actin complex. We show
      that cross-linking reduces the rotational mobility of an attached probe. It is
      consistent with the filaments becoming more rigid. Addition of heavy meromyosin
      (HMM) to the cross-linked filaments further restricts the rotational mobility of
      the probe. The effect of HMM on the actin filaments is highly cooperative: even a
      1 : 10 molar ratio of HMM to actin strongly restricts the dynamics of the
      filaments. More interesting results are obtained when nucleotides are also added.
      In the presence of HMM and ADP, similar strongly reduced mobility of the probe
      was found than in a rigor state. In the presence of adenosine 5'[betagamma-imido]
      triphosphate (AMPPNP), a nonhydrolyzable analogue of ATP, weak binding of HMM to
      either cross-linked or native F-actin increases probe mobility. By contrast, weak
      binding by the HMM/ADP/AlF4 complex has different effects upon the two systems.
      This protein-nucleotide complex increases probe mobility in native actin
      filaments, as does HMM + AMPPNP. However, its addition to cross-linked filaments
      leaves probe mobility as constrained as in the rigor state. These findings
      suggest that the dynamic change upon weak binding by HMM/ADP/AlF4 which is
      inhibited by cross-linking is essential to the proper mechanical behaviour of the
      filaments during movement.

PMID- 16640555
TI  - Enhanced stereoselective hydrolysis of toxic organophosphates by directly evolved
      variants of mammalian serum paraoxonase.
AB  - We addressed the ability of various organophosphorus (OP) hydrolases to
      catalytically scavenge toxic OP nerve agents. Mammalian paraoxonase (PON1) was
      found to be more active than Pseudomonas diminuta OP hydrolase (OPH) and squid
      O,O-di-isopropyl fluorophosphatase (DFPase) in detoxifying cyclosarin (O
      cyclohexyl methylphosphonofluoridate) and soman (O-pinacolyl
      methylphosphonofluoridate). Subsequently, nine directly evolved PON1 variants,
      selected for increased hydrolytic rates with a fluorogenic diethylphosphate
      ester, were tested for detoxification of cyclosarin, soman, O-isopropyl-O-(p
      nitrophenyl) methyl phosphonate (IMP-pNP), DFP, and chlorpyrifos-oxon (ChPo).
      Detoxification rates were determined by temporal acetylcholinesterase inhibition
      by residual nonhydrolyzed OP. As stereoisomers of cyclosarin and soman differ
      significantly in their acetylcholinesterase-inhibiting potency, we actually
      measured the hydrolysis of the more toxic stereoisomers. Cyclosarin
      detoxification was approximately 10-fold faster with PON1 mutants V346A and L69V.
      V346A also exhibited fourfold and sevenfold faster hydrolysis of DFP and ChPo,
      respectively, compared with wild-type, and ninefold higher activity towards
      soman. L69V exhibited 100-fold faster hydrolysis of DFP than the wild-type. The
      active-site mutant H115W exhibited 270-380-fold enhancement toward hydrolysis of
      the P-S bond in parathiol, a phosphorothiolate analog of parathion. This study
      identifies three key positions in PON1 that affect OP hydrolysis, Leu69, Val346
      and His115, and several amino-acid replacements that significantly enhance the
      hydrolysis of toxic OPs. GC/pulsed flame photometer detector analysis, compared
      with assay of residual acetylcholinesterase inhibition, displayed stereoselective
      hydrolysis of cyclosarin, soman, and IMP-pNP, indicating that PON1 is less active
      toward the more toxic optical isomers.

PMID- 16640556
TI  - The narrow substrate specificity of human tyrosine aminotransferase--the enzyme
      deficient in tyrosinemia type II.
AB  - Human tyrosine aminotransferase (hTATase) is the pyridoxal phosphate-dependent
      enzyme that catalyzes the reversible transamination of tyrosine to p
      hydrophenylpyruvate, an important step in tyrosine metabolism. hTATase deficiency
      is implicated in the rare metabolic disorder, tyrosinemia type II. This enzyme is
      a member of the poorly characterized Igamma subfamily of the family I
      aminotransferases. The full length and truncated forms of recombinant hTATase
      were expressed in Escherichia coli, and purified to homogeneity. The pH-dependent
      titration of wild-type reveals a spectrum characteristic of family I
      aminotransferases with an aldimine pK(a) of 7.22. I249A mutant hTATase exhibits
      an unusual spectrum with a similar aldimine pK(a) (6.85). hTATase has very narrow
      substrate specificity with the highest enzymatic activity for the Tyr/alpha
      ketoglutarate substrate pair, which gives a steady state k(cat) value of 83 s(
      1). In contrast there is no detectable transamination of aspartate or other
      cosubstrates. The present findings show that hTATase is the only known
      aminotransferase that discriminates significantly between Tyr and Phe: the
      k(cat)/K(m) value for Tyr is about four orders of magnitude greater than that for
      Phe. A comparison of substrate specificities of representative Ialpha and Igamma
      aminotransferases is described along with the physiological significance of the
      discrimination between Tyr and Phe by hTATase as applied to the understanding of
      the molecular basis of phenylketonuria.

PMID- 16640557
TI  - The calcium-binding domain of the stress protein SEP53 is required for survival
      in response to deoxycholic acid-mediated injury.
AB  - Stress protein responses have evolved in part as a mechanism to protect cells
      from the toxic effects of environmental damaging agents. Oesophageal squamous
      epithelial cells have evolved an atypical stress response that results in the
      synthesis of a 53 kDa protein of undefined function named squamous epithelial
      induced stress protein of 53 kDa (SEP53). Given the role of deoxycholic acid
      (DCA) as a potential damaging agent in squamous epithelium, we developed assays
      measuring the effects of DCA on SEP53-mediated responses to damage. To achieve
      this, we cloned the human SEP53 gene, developed a panel of monoclonal antibodies
      to the protein, and showed that SEP53 expression is predominantly confined to
      squamous epithelium. Clonogenic assays were used to show that SEP53 can function
      as a survival factor in mammalian cell lines, can attenuate DCA-induced apoptotic
      cell death, and can attenuate DCA-mediated increases in intracellular free
      calcium. Deletion of the highly conserved EF-hand calcium-binding domain in SEP53
      neutralizes the colony survival activity of the protein, neutralizes the
      protective effects of SEP53 after DCA exposure, and permits calcium elevation in
      response to DCA challenge. These data indicate that the squamous cell-stress
      protein SEP53 can function as a modifier of the DCA-mediated calcium influx and
      identify a novel survival pathway whose study may shed light on mechanisms
      relating to squamous cell injury and associated cancer development.

PMID- 16640558
TI  - Functional characterization of hepatocyte nuclear factor-4 alpha dimerization
      interface mutants.
AB  - Hepatocyte nuclear factor-4 (HNF-4alpha), a member of the nuclear receptor
      superfamily, binds DNA exclusively as a homodimer. Dimerization controls
      important aspects of receptor function, such as DNA binding, protein stability,
      ligand binding and interaction with coactivators. Crystallographic data of the
      HNF-4alpha ligand-binding domain (LBD) demonstrated that the homodimer interface
      is composed of residues in helices 7, 9 and 10 with intermolecular salt bridges,
      hydrogen bonds and hydrophobic interactions contributing to the stability of the
      interface. To investigate the importance of the proposed ionic interactions for
      HNF-4alpha dimerization, interactions critical for formation of the LBD homodimer
      interface were disrupted by introducing point mutations in residues D261N (H7),
      E269Q (H7), Q307L (H9), D312N (H9) and Q336L (H10). Mutants were analysed for
      transactivation, coactivator interaction, DNA binding and dimerization. EMSA
      analysis showed that the mutants are able to bind DNA as dimers and
      coimmunoprecipitation assays confirmed dimerization in solution. Furthermore, the
      mutations do not compromise HNF-4alpha activity and are responsive to PPAR-gamma
      coactivator-1 (PGC-1). Finally, residue R324, located in the H9/H10 loop, which
      was suspected to be involved in dimer stabilization via an ionic interaction with
      residue E276, was studied. In contrast to the conservative substitution R324H the
      mutation R324L abolishes HNF-4alpha transcriptional activity and coactivator
      recruitment, revealing that the nature of substitution may play an important role
      in HNF-4alpha function.

PMID- 16640559
TI  - Copper-dependent degradation of recombinant ovine prion protein.
      Phosphatidylinositol stimulates aggregation and copper-driven disappearance of
      prion protein.
AB  - Prion protein (PrP) plays an important role in cell protection from oxidative
      stress due to its action as copper-chelating protein. The present study
      demonstrates that PrP participates in reductions of Cu2+ to Cu+ ions, and that
      this process results in fragmentation of protein. The interaction with
      phosphatidylinositol, a natural phospholipid moiety bound to PrP, strongly
      enhances recombinant PrP aggregation and degradation. The copper-dependent PrP
      degradation could promote the formation of amyloid structures, destabilizing the
      PrP soluble form by the cleavage of the N-terminal part.

PMID- 16640560
TI  - A unique binding epitope for salvinorin A, a non-nitrogenous kappa opioid
      receptor agonist.
AB  - Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique
      structural and pharmacological properties. This non-nitrogenous ligand lacks
      nearly all the structural features commonly associated with opioid ligand binding
      and selectivity. This study explores the structural basis to salvinorin A binding
      and selectivity using a combination of chimeric and single-point mutant opioid
      receptors. The experiments were designed based on previous models of salvinorin A
      that locate the ligand within a pocket formed by transmembrane (TM) II, VI, and
      VII. More traditional sites of opioid recognition were also explored, including
      the highly conserved aspartate in TM III (D138) and the KOP selectivity site
      E297, to determine the role, if any, that these residues play in binding and
      selectivity. The results indicate that salvinorin A recognizes a cluster of
      residues in TM II and VII, including Q115, Y119, Y312, Y313, and Y320. Based on
      the position of these residues within the receptor, and prior study on salvinorin
      A, a model is proposed that aligns the ligand vertically, between TM II and VII.
      In this orientation, the ligand spans residues that are spaced one to two turns
      down the face of the helices within the receptor cavity. The ligand is also in
      close proximity to EL-2 which, based on chimeric data, is proposed to play an
      indirect role in salvinorin A binding and selectivity.

PMID- 16640561
TI  - Determining and understanding the control of glycolysis in fast-growth tumor
      cells. Flux control by an over-expressed but strongly product-inhibited
      hexokinase.
AB  - Control analysis of the glycolytic flux was carried out in two fast-growth tumor
      cell types of human and rodent origin (HeLa and AS-30D, respectively).
      Determination of the maximal velocity (V(max)) of the 10 glycolytic enzymes from
      hexokinase to lactate dehydrogenase revealed that hexokinase (153-306 times) and
      phosphofructokinase-1 (PFK-1) (22-56 times) had higher over-expression in rat AS
      30D hepatoma cells than in normal freshly isolated rat hepatocytes. Moreover, the
      steady-state concentrations of the glycolytic metabolites, particularly those of
      the products of hexokinase and PFK-1, were increased compared with hepatocytes.
      In HeLa cells, V(max) values and metabolite concentrations for the 10 glycolytic
      enzyme were also significantly increased, but to a much lesser extent (6-9 times
      for both hexokinase and PFK-1). Elasticity-based analysis of the glycolytic flux
      in AS-30D cells showed that the block of enzymes producing Fru(1,6)P2 (i.e.
      glucose transporter, hexokinase, hexosephosphate isomerase, PFK-1, and the Glc6P
      branches) exerted most of the flux control (70-75%), whereas the consuming block
      (from aldolase to lactate dehydrogenase) exhibited the remaining control. The
      Glc6P-producing block (glucose transporter and hexokinase) also showed high flux
      control (70%), which indicated low flux control by PFK-1. Kinetic analysis of PFK
      1 showed low sensitivity towards its allosteric inhibitors citrate and ATP, at
      physiological concentrations of the activator Fru(2,6)P2. On the other hand,
      hexokinase activity was strongly inhibited by high, but physiological,
      concentrations of Glc6P. Therefore, the enhanced glycolytic flux in fast-growth
      tumor cells was still controlled by an over-produced, but Glc6P-inhibited
      hexokinase.

PMID- 16640562
TI  - Increased sensitivity of glycogen synthesis to phosphorylase-a and impaired
      expression of the glycogen-targeting protein R6 in hepatocytes from insulin
      resistant Zucker fa/fa rats.
AB  - Hepatic insulin resistance in the leptin-receptor defective Zucker fa/fa rat is
      associated with impaired glycogen synthesis and increased activity of
      phosphorylase-a. We investigated the coupling between phosphorylase-a and
      glycogen synthesis in hepatocytes from fa/fa rats by modulating the concentration
      of phosphorylase-a. Treatment of hepatocytes from fa/fa rats and Fa/? controls
      with a selective phosphorylase inhibitor caused depletion of phosphorylase-a,
      activation of glycogen synthase and stimulation of glycogen synthesis. The flux
      control coefficient of phosphorylase on glycogen synthesis was glucose dependent
      and at 10 mm glucose was higher in fa/fa than Fa/? hepatocytes. There was an
      inverse correlation between the activities of glycogen synthase and phosphorylase
      a in both fa/fa and Fa/? hepatocytes. However, fa/fa hepatocytes had a higher
      activity of phosphorylase-a, for a corresponding activity of glycogen synthase.
      This defect was, in part, normalized by expression of the glycogen-targeting
      protein, PTG. Hepatocytes from fa/fa rats had normal expression of the glycogen
      targeting proteins G(L) and PTG but markedly reduced expression of R6. Expression
      of R6 protein was increased in hepatocytes from Wistar rats after incubation with
      leptin and insulin. Diminished hepatic R6 expression in the leptin-receptor
      defective fa/fa rat may be a contributing factor to the elevated phosphorylase
      activity and/or its high control strength on glycogen synthesis.

PMID- 16640563
TI  - p130-angiomotin associates to actin and controls endothelial cell shape.
AB  - Angiomotin, an 80 kDa protein expressed in endothelial cells, promotes cell
      migration and invasion, and stabilizes tube formation in vitro. Angiomotin
      belongs to a new protein family with two additional members, Amotl-1 and Amotl-2,
      which are characterized by conserved coiled-coil domains and C-terminal PDZ
      binding motifs. Here, we report the identification of a 130 kDa splice isoform of
      angiomotin that is expressed in different cell types including vascular
      endothelial cells, as well as cytotrophoblasts of the placenta. p130-Angiomotin
      consists of a cytoplasmic N-terminal extension that mediates its association with
      F-actin. Transfection of p130-angiomotin into endothelial cells induces actin
      fiber formation and changes cell shape. The p130-angiomotin protein remained
      associated with actin after destabilization of actin fibers with cytochalasin B.
      In contrast to p80-angiomotin, p130-angiomotin does not promote cell migration
      and did not respond to angiostatin. We propose that p80- and p130-angiomotin play
      coordinating roles in tube formation by affecting cell migration and cell shape,
      respectively.

PMID- 16640564
TI  - Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its
      role in leucine metabolism.
AB  - The metabolic disease 3-methylglutaconic aciduria type I (MGA1) is characterized
      by an abnormal organic acid profile in which there is excessive urinary excretion
      of 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxyisovaleric acid.
      Affected individuals display variable clinical manifestations ranging from mildly
      delayed speech development to severe psychomotor retardation with neurological
      handicap. MGA1 is caused by reduced or absent 3-methylglutaconyl-coenzyme A (3-MG
      CoA) hydratase activity within the leucine degradation pathway. The human AUH
      gene has been reported to encode for a bifunctional enzyme with both RNA-binding
      and enoyl-CoA-hydratase activity. In addition, it was shown that mutations in the
      AUH gene are linked to MGA1. Here we present kinetic data of the purified gene
      product of AUH using different CoA-substrates. The best substrates were (E)-3-MG
      CoA (V(max) = 3.9 U.mg(-1), K(m) = 8.3 microM, k(cat) = 5.1 s(-1)) and (E)
      glutaconyl-CoA (V(max) = 1.1 U.mg(-1), K(m) = 2.4 microM, k(cat) = 1.4 s(-1))
      giving strong evidence that the AUH gene encodes for the major human 3-MG-CoA
      hydratase in leucine degradation. Based on these results, a new assay for AUH
      activity in fibroblast homogenates was developed. The only missense mutation
      found in MGA1 phenotypes, c.719C>T, leading to the amino acid exchange A240V,
      produces an enzyme with only 9% of the wild-type 3-MG-CoA hydratase activity.

PMID- 16640565
TI  - Receptor association and tyrosine phosphorylation of S6 kinases.
AB  - Ribosomal protein S6 kinase (S6K) is activated by an array of mitogenic stimuli
      and is a key player in the regulation of cell growth. The activation process of
      S6 kinase involves a complex and sequential series of multiple Ser/Thr
      phosphorylations and is mainly mediated via phosphatidylinositol 3-kinase (PI3K)
      3-phosphoinositide-dependent protein kinase-1 (PDK1) and mTor-dependent pathways.
      Upstream regulators of S6K, such as PDK1 and protein kinase B (PKB/Akt), are
      recruited to the membrane via their pleckstrin homology (PH) or protein-protein
      interaction domains. However, the mechanism of integration of S6K into a multi
      enzyme complex around activated receptor tyrosine kinases is not clear. In the
      present study, we describe a specific interaction between S6K with receptor
      tyrosine kinases, such as platelet-derived growth factor receptor (PDGFR). The
      interaction with PDGFR is mediated via the kinase or the kinase extension domain
      of S6K. Complex formation is inducible by growth factors and leads to S6K
      tyrosine phosphorylation. Using PDGFR mutants, we have shown that the
      phosphorylation is exerted via a PDGFR-src pathway. Furthermore, src kinase
      phosphorylates and coimmunoprecipitates with S6K in vivo. Inhibitors towards
      tyrosine kinases, such as genistein and PP1, or src-specific SU6656, but not PI3K
      and mTor inhibitors, lead to a reduction in tyrosine phosphorylation of S6K. In
      addition, we mapped the sites of tyrosine phosphorylation in S6K1 and S6K2 to Y39
      and Y45, respectively. Mutational and immunofluorescent analysis indicated that
      phosphorylation of S6Ks at these sites does not affect their activity or
      subcellular localization. Our data indicate that S6 kinase is recruited into a
      complex with RTKs and src and becomes phosphorylated on tyrosine/s in response to
      PDGF or serum.

PMID- 16640566
TI  - Domain deletions and substitutions in the modular protein evolution.
AB  - The main mechanisms shaping the modular evolution of proteins are gene
      duplication, fusion and fission, recombination and loss of fragments. While a
      large body of research has focused on duplications and fusions, we concentrated,
      in this study, on how domains are lost. We investigated motif databases and
      introduced a measure of protein similarity that is based on domain arrangements.
      Proteins are represented as strings of domains and comparison was based on the
      classic dynamic alignment scheme. We found that domain losses and duplications
      were more frequent at the ends of proteins. We showed that losses can be
      explained by the introduction of start and stop codons which render the terminal
      domains nonfunctional, such that further shortening, until the whole domain is
      lost, is not evolutionarily selected against. We demonstrated that domains which
      also occur as single-domain proteins are less likely to be lost at the N terminus
      and in the middle, than at the C terminus. We conclude that fission/fusion events
      with single-domain proteins occur mostly at the C terminus. We found that domain
      substitutions are rare, in particular in the middle of proteins. We also showed
      that many cases of substitutions or losses result from erroneous annotations, but
      we were also able to find courses of evolutionary events where domains vanish
      over time. This is explained by a case study on the bacterial formate
      dehydrogenases.

PMID- 16640567
TI  - Neuropeptide Y-family receptors Y6 and Y7 in chicken. Cloning, pharmacological
      characterization, tissue distribution and conserved synteny with human chromosome
      region.
AB  - The peptides of the neuropeptide Y (NPY) family exert their functions, including
      regulation of appetite and circadian rhythm, by binding to G-protein coupled
      receptors. Mammals have five subtypes, named Y1, Y2, Y4, Y5 and Y6, and recently
      Y7 has been discovered in fish and amphibians. In chicken we have previously
      characterized the first four subtypes and here we describe Y6 and Y7. The genes
      for Y6 and Y7 are located 1 megabase apart on chromosome 13, which displays
      conserved synteny with human chromosome 5 that harbours the Y6 gene. The porcine
      PYY radioligand bound the chicken Y6 receptor with a K(d) of 0.80 +/- 0.36 nm. No
      functional coupling was demonstrated. The Y6 mRNA is expressed in hypothalamus,
      gastrointestinal tract and adipose tissue. Porcine PYY bound chicken Y7 with a
      K(d) of 0.14 +/- 0.01 nm (mean +/- SEM), whereas chicken PYY surprisingly had a
      much lower affinity, with a Ki of 41 nm, perhaps as a result of its additional
      amino acid at the N terminus. Truncated peptide fragments had greatly reduced
      affinity for Y7, in agreement with its closest relative, Y2, in chicken and fish,
      but in contrast to Y2 in mammals. This suggests that in mammals Y2 has only
      recently acquired the ability to bind truncated PYY. Chicken Y7 has a much more
      restricted tissue distribution than other subtypes and was only detected in
      adrenal gland. Y7 seems to have been lost in mammals. The physiological roles of
      Y6 and Y7 remain to be identified, but our phylogenetic and chromosomal analyses
      support the ancient origin of these Y receptor genes by chromosome duplications
      in an early (pregnathostome) vertebrate ancestor.

PMID- 16640568
TI  - New taxonomic concepts for the important forest pathogen Cryphonectria parasitica
      and related fungi.
AB  - Species of Cryphonectria include some of the world's most important and
      devastating tree pathogens. Largely through the application of DNA sequence
      phylogenies, the taxonomy of these fungi has undergone major changes in recent
      years. Cryphonectria, including the chestnut blight pathogen Cryphonectria
      parasitica, has been restricted to species that have semi-immersed stromata,
      orange and pulvinate conidiomata, and one-septate ascospores. Other species of
      Cryphonectria with different morphological characteristics have been transferred
      to new genera that are strongly supported by phylogenetic data. This review
      represents a summary of the taxonomic changes to species of Cryphonectria sensu
      lato, and we discuss the impact that these changes might have on the
      understanding of their ecology, pathology and worldwide distribution.

PMID- 16640569
TI  - Characterization of a c-type heme-containing PAS sensor domain from Geobacter
      sulfurreducens representing a novel family of periplasmic sensors in
      Geobacteraceae and other bacteria.
AB  - Geobacter sulfurreducens encodes one of the largest numbers of proteins annotated
      as parts of the two-component signal transduction and/or chemotaxis pathways. Ten
      of these signal transducers have homologous periplasmic sensor domains that
      contain the sequence signature for c-type hemes. One such sensor domain encoded
      by gene GSU0303 was isolated and characterized. The protein was expressed in
      Escherichia coli and was isolated as two colored species (green and red). The
      green species is a monomer of the sensor domain with a five-coordinated high-spin
      heme and the red species is probably a noncovalent dimer of the sensor domain
      which might have an uncharacterized ligand bound to the dimer. The UV-VIS
      spectrum of the green species indicates that it has a c'-type heme, but its
      structure is predicted to be homologous to CitA, a periplasmic PAS domain that
      does not contain heme. The GSU0303 sensor domain represents a previously
      unreported family of PAS-type periplasmic sensor domains that contain c-type
      hemes; these proteins could be part of an important mechanism for sensing redox
      potential or small ligands in the periplasm. Homologs to the sensor domains we
      identified in G. sulfurreducens are observed in various bacteria although they
      occur in larger numbers in the Geobacteraceae.

PMID- 16640570
TI  - Isolation and characterization of bacteriophages infecting Salmonella spp.
AB  - Bacteriophages infecting Salmonella spp. were isolated from sewage using soft
      agar overlays containing three Salmonella serovars and assessed with regard to
      their potential to control food-borne salmonellae. Two distinct phages, as
      defined by plaque morphology, structure and host range, were obtained from a
      single sample of screened sewage. Phage FGCSSa1 had the broadest host range
      infecting six of eight Salmonella isolates and neither of two Escherichia coli
      isolates. Under optimal growth conditions for S. Enteritidis PT160, phage
      infection resulted in a burst size of 139 PFU but was apparently inactive at a
      temperature typical of stored foods (5 degrees C), even at multiplicity of
      infection values in excess of 10 000. While neither isolate had characteristics
      that would make them candidates for biocontrol of Salmonella spp. in foods, phage
      FGCSSa1 behaved unusually when grown on two Salmonella serotypes at 37 degrees C
      in that the addition of phages appeared to retard growth of the host, presumably
      by the lysis of a fraction of the host cell population.

PMID- 16640571
TI  - The WD-40 repeat protein PkwA of Thermomonospora curvata is associated with rapid
      growth and is localized in the tips of growing hyphae.
AB  - The PkwA protein of the thermophilic actinomycete Thermomonospora curvata has
      already been reported as the first instance of a WD-40 module-containing protein
      of prokaryotic origin. This protein is composed of an N-terminal eukaryotic-type
      protein kinase domain and of seven C-terminal WD-40 repeats. PkwA is a peripheral
      membrane protein that is linked to the early exponential growth phase of the
      bacterium. Its intracellular concentrations are extremely low. We have shown that
      the protein forms high molecular weight complexes and is localized mainly in the
      tips of the young Thermomonospora vegetative hyphae.

PMID- 16640572
TI  - Comparison of Vibrio harveyi strains isolated from shrimp farms and from culture
      collection in terms of toxicity and antibiotic resistance.
AB  - Vibrio harveyi strains isolated from shrimp farms (wild strains) were compared
      with those from culture collections in terms of minimum inhibitory concentration
      (MIC) and toxicity. Wild strains had higher MIC values for four antibiotics
      (kanamycin, carbenicillin, oxytetracycline and ampicillin) and also showed higher
      toxicity compared with culture collection strains. Vibrio harveyi with the lowest
      antibacterial resistance was chosen to test if a gradual increase in antibiotic
      concentration and frequent subculture would enhance its antibiotic resistance.
      Results showed that V. harveyi was able to develop resistance to oxytetracycline.
      The MIC value was 250 times higher compared with the MIC before subculturing.
      Moreover, the V. harveyi strain developed slightly higher toxicity. Therefore, it
      is possible that there is a relationship between antibiotic resistance and
      toxicity in V. harveyi.

PMID- 16640573
TI  - The potential of azole antifungals against latent/persistent tuberculosis.
AB  - The aim of the present study was to evaluate the chemotherapeutic potential of
      econazole against latent tuberculosis. The activity of econazole and clotrimazole
      was tested against the latent bacilli (Mycobacterium tuberculosis H(37)Rv)
      developed by nutrient starvation under in vitro conditions and by drugs under in
      vivo conditions. The latent bacteria developed under in vitro latent conditions
      were acid-fast negative, nonreplicating, resistant to conventional antitubercular
      drugs and showed low respiration rates. Econazole as well as clotrimazole were
      found to have strong antimycobacterial potential against latent Mycobacterium
      tuberculosis under in vitro conditions as seen by reductions in colony-forming
      units. Further, econazole prevented the formation of drug-induced latency and
      significantly reduced bacterial burden from lungs and spleens of latent
      tuberculosis-infected mice. We conclude that azole drugs bear significant
      therapeutic potential against latent tuberculosis.

PMID- 16640574
TI  - Characterization of the Legionella anisa population structure by pulsed-field gel
      electrophoresis.
AB  - We analysed 38 French isolates of Legionella anisa by means of pulsed-field gel
      electrophoresis (PFGE) with single or double digestion. Double digestion was more
      discriminatory than single digestion, and can thus be useful for epidemiological
      studies of L. anisa. Several isolates from different parts of France clustered
      together on the basis of their PFGE patterns (similarity cutoff of 80%),
      suggesting that the L. anisa population structure is homogenous or that a few
      clones of L. anisa strains have spread widely in France.

PMID- 16640575
TI  - Leucocins 4010 from Leuconostoc carnosum cause a matrix related decrease in
      intracellular pH of Listeria monocytogenes.
AB  - A mixed culture of single cells of Listeria monocytogenes and the bacteriocin
      producing Leuconostoc carnosum 4010 showed growth inhibition of L. monocytogenes,
      although the intracellular pH (pHi) of L. monocytogenes followed by fluorescence
      ratio imaging microscopy was not affected. Furthermore, L. monocytogenes was
      exposed to the bacteriocins leucocins 4010 and nisin either in a liquid filled
      chamber or on the surface of an agar containing bacteriocins. Both bacteriocins
      caused dissipation of the pH gradient in L. monocytogenes and the effect was
      clearly dependent on the matrix, as the decrease in pHi occurred much more
      rapidly in liquid than in agar.

PMID- 16640576
TI  - Iron depletion affects nitrogenase activity and expression of nifH and nifA genes
      in Herbaspirillum seropedicae.
AB  - Herbaspirillum seropedicae Z67 is a nitrogen-fixing bacterium able to colonize
      the rhizosphere and the interior of several plants. As iron is a key element for
      nitrogen fixation, we examined the response of this microorganism to iron
      deficiency under nitrogen fixing conditions. We identified a H. seropedicae exbD
      gene that was induced in response to iron limitation and is involved in iron
      homeostasis. We found that an exbD mutant grown in iron-chelated medium is unable
      to fix nitrogen. Moreover, we provide evidence that expression of the nifH and
      nifA genes is iron dependent in a H. seropedicae genetic background.

PMID- 16640577
TI  - Construction and characterization of Bacillus subtilis deletion mutants lacking
      the prophage 2-trnS region.
AB  - During development of a novel method for constructing a series of deletions in
      Bacillus subtilis using an isogenic set of gene-disrupted mutants created by
      integration of pMutin, deletion of the trnS operon, consisting of seven tRNA
      genes, was found to affect cell growth, development of competence and spore
      formation. A suppressor (sts1) of the DeltatrnS mutant was isolated, sequenced
      and found to have undergone a single base change, CAG to GAG, in the first
      anticodon of tRNA(Leu), in the trnB operon.

PMID- 16640578
TI  - Type II quorum sensing regulates virulence in Erwinia carotovora ssp. carotovora.
AB  - Quorum sensing is a process by which bacteria communicate using secreted chemical
      signaling molecules called autoinducers. In this study, the opportunistic plant
      pathogen Erwinia carotovora ssp. carotovora was observed to secrete type II
      signaling molecules. A homolog of luxS, the gene required for AI-2 synthesis in
      Vibrio harveyi, was isolated from the genome of the pathogen. To determine the
      potential role of AI-2 in virulence, an isogenic luxS- (ECC) mutant was
      constructed and tested for its ability to cause tissue maceration. The findings
      reported here demonstrate that the LuxS-dependent signaling affects the
      progression of disease symptoms during the early stages of infection by
      modulating the expression of pectinolytic enzymes.

PMID- 16640579
TI  - Utilization of myoglobin as a heme source by Haemophilus influenzae requires
      binding of myoglobin to haptoglobin.
AB  - Haemophilus influenzae has an absolute growth requirement for heme. One potential
      in vivo source of heme is the protein myoglobin which is found at low levels in
      human serum. No tested H. influenzae strain was able to use myoglobin as a heme
      source. However, all strains were able to utilize the heme from myoglobin when
      myoglobin was complexed with haptoglobin. Utilization of the haptoglobin
      myoglobin complex was shown to be mediated by the previously described
      hemoglobin/hemoglobin-haptoglobin-binding proteins of H. influenzae.

PMID- 16640580
TI  - Molecular cloning of AbGst1 encoding a glutathione transferase differentially
      expressed during exposure of Alternaria brassicicola to isothiocyanates.
AB  - The AbGst1 gene encoding a glutathione transferase from the necrotrophic pathogen
      Alternaria brassicicola was cloned from a benzyl isothiocyanate-treated conidial
      culture using differential display reverse transcription. The deduced amino-acid
      sequence of AbGst1p showed a significant degree of similarity to glutathione
      transferase-I from Saccharomyces cerevisiae and glutathione transferase-III from
      Schizosaccharomyces pombe. The transcription of AbGst1 was significantly enhanced
      by isothiocyanates, heavy metals and 1-chloro-2,4-dinitrobenzene. However, no
      significant transcript response was obtained with superoxide-generating menadione
      and paraquat. Recombinant AbGst1p expressed in Escherichia coli exhibited high
      transferase activity with allyl and benzyl isothiocyanates as substrate compared
      with 1-chloro-2,4-dinitrobenzene, but no peroxidase activity was detected. AbGst1
      was upregulated in planta during the first day postinfection, suggesting the
      potential involvement of this enzyme in isothiocyanate detoxification mechanisms
      during host plant infection.

PMID- 16640581
TI  - Cross-talk towards the response regulator NtrC controlling nitrogen metabolism in
      Rhodobacter capsulatus.
AB  - Rhodobacter capsulatus NtrB/NtrC two-component regulatory system controls
      expression of genes involved in nitrogen metabolism including urease and nitrogen
      fixation genes. The ntrY-ntrX genes, which are located immediately downstream of
      the nifR3-ntrB-ntrC operon, code for a two-component system of unknown function.
      Transcription of ntrY starts within the ntrC-ntrY intergenic region as shown by
      primer extension analysis, but maximal transcription requires, in addition, the
      promoter of the nifR3-ntrB-ntrC operon. While ntrB and ntrY single mutant strains
      were able to grow with either urea or N2 as sole nitrogen source, a ntrB/ntrY
      double mutant (like a ntrC-deficient strain) was no longer able to use urea or
      N2. These findings suggest that the histidine kinases NtrB and NtrY can
      substitute for each other as phosphodonors towards the response regulator NtrC.

PMID- 16640582
TI  - Determining the antibiotic resistance potential of the indigenous oral microbiota
      of humans using a metagenomic approach.
AB  - Studies of the prevalence and identity of genes encoding resistance to
      antibiotics in a microbial community are usually carried out on only the
      cultivable members of the community. However, it is possible to include the as
      yet-uncultivable organisms present by adopting a metagenomic approach to such
      studies. In this investigation, four metagenomic libraries of the oral microbiota
      were prepared from three groups of 20 adult humans and screened for antibiotic
      resistant clones. Clones resistant to tetracycline and amoxycillin were present
      in all four libraries while gentamicin-resistant clones were found in three of
      the libraries. The genes encoding tetracycline resistance in the clones were
      identified and found to be tet(M), tet(O), tet(Q), tet(W), tet37 and tet(A).
      However, only the first three of these were detected in all three groups of
      individuals investigated.

PMID- 16640583
TI  - Glycosylation of flavonoids with a glycosyltransferase from Bacillus cereus.
AB  - Microbial glycosyltransferases can convert many small lipophilic compounds such
      as phenolics, terpenoids, cyanohydrins and alkaloids into glycons using uridine
      diphosphate-activated sugars. The main chemical functions of glycosylation
      processes are stabilization, detoxification and solubilization of the substrates.
      The gene encoding the UDP-glycosyltransferase from Bacillus cereus, BcGT-1, was
      cloned by PCR and sequenced. BcGT-1 was expressed in Escherichia coli BL21 (DE3)
      with a his-tag and purified using a His-tag affinity column. BcGT-1 could use
      apigenin, genistein, kaempferol, luteolin, naringenin and quercetin as substrates
      and gave two reaction products. The enzyme preferentially glycosylated at the 3
      hydroxyl group, but it could transfer a glucose group onto the 7-hydroxyl group
      when the 3-hydroxyl group was not available. The reaction products made by
      biotransformation of flavonoids with E. coli expressing BcGT-1 are similar to
      those produced with the purified recombinant enzyme. Thus, this work provides a
      method that might be useful for the biosynthesis of flavonoid glucosides and for
      the glycosylation of related compounds.

PMID- 16640584
TI  - Methanogenesis is Ca2+ dependent in Methanothermobacter thermautotrophicus strain
      DeltaH.
AB  - The effect of Ca2+ ions on methanogenesis and growth of Methanothermobacter
      thermautotrophicus was investigated. The calcium chelator ethylene glycol bis(2
      aminoethylether)-N,N,N',N'-tetra-acetic acid, calcium ionophore A23187 and
      ruthenium red all inhibited growth of this strain. Methane formation was strongly
      dependent on the external Ca2+ concentration in a resting cell suspension. In
      addition, methanogenesis of Ca2+ preloaded cells was stimulated by 400%.
      Inhibitor studies revealed that Co2+ and Ni2+, inorganic antagonists of Ca2+
      transport, strongly inhibited methanogenesis in these cells. Interestingly, our
      findings imply that one of the enzymes of methanogenesis might catalyse a Ca2+ 
      dependent step and allow a direct activation of methanogenesis by Ca2+ ions.

PMID- 16640585
TI  - Characterization of adhesin variants in Indian isolates of enteroaggregative
      Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC) are causative agents of diarrhea, being
      characterized by aggregative adherence to cultured epithelial cells. In this
      study, phenotypic properties of EAEC were analyzed with respect to AA,
      hemagglutination, clump and biofilm formation, all of which are mediated by
      aggregative adherence fimbriae (AAF). The strains were also screened for AAF
      types, AAF adhesin variants and Dr adhesin by PCR. Of the three known AAF types,
      AAF/I and AAF/II adhesin variants were identified. An association between the
      AAF/adhesin genotypes and the subtypes/scores of phenotypic properties was sought
      and it was observed that strains harboring same adhesins displayed different
      subtypes/scores and vice versa.

PMID- 16640586
TI  - Microbial desulfurization of gasoline by free whole-cells of Rhodococcus
      erythropolis XP.
AB  - Rhodococcus erythropolis XP could grow well with condensed thiophenes, mono
      thiophenic compounds and mercaptans present in gasoline. Rhodococcus erythropolis
      XP was also capable of efficiently degrading the condensed thiophenes in resting
      cell as well as biphasic reactions in which n-octane served as a model oil phase.
      Free whole cells of R. erythropolis XP were adopted to desulfurize fluid
      catalytic cracking (FCC) and straight-run (SR) gasoline oils. About 30% of the
      sulfur content of FCC gasoline and 85% of sulfur in SR gasoline were reduced,
      respectively. Gas chromatography analysis with atomic emission detection also
      showed depletion of sulfur compounds in SR gasoline. Rhodococcus erythropolis XP
      could partly resist the toxicity of gasoline and had an application potential to
      biodesulfurization of gasoline.

PMID- 16640587
TI  - Clumping factor A of Staphylococcus aureus inhibits phagocytosis by human
      polymorphonuclear leucocytes.
AB  - Staphylococcus aureus is a major cause of nosocomial and community-acquired
      infection. It expresses several factors that promote avoidance of phagocytosis by
      polymorphonuclear leucocytes. Clumping factor A (ClfA) is a fibrinogen-binding
      surface protein of S. aureus that is an important virulence factor in several
      infection models. This study investigated whether ClfA is an antiphagocytic
      factor, and whether its antiphagocytic properties were based on its ability to
      bind fibrinogen. In S. aureus, ClfA was shown to be of equal importance to
      protein A, the antiphagocytic properties of which are well established. ClfA
      expressed in a surrogate Gram-positive host was also found to be antiphagocytic.
      A ClfA mutant that was unable to bind fibrinogen had a similar antiphagocytic
      effect to native ClfA in the absence of fibrinogen. ClfA inhibited phagocytosis
      in the absence of fibrinogen, and showed enhanced inhibition in the presence of
      fibrinogen.

PMID- 16640588
TI  - Ladderane phospholipids in anammox bacteria comprise phosphocholine and
      phosphoethanolamine headgroups.
AB  - Anammox bacteria present in wastewater treatment systems and marine environments
      are capable of anaerobically oxidizing ammonium to dinitrogen gas. This anammox
      metabolism takes place in the anammoxosome which membrane is composed of lipids
      with peculiar staircase-like 'ladderane' hydrocarbon chains that comprise three
      or four linearly concatenated cyclobutane structures. Here, we applied high
      performance liquid chromatography coupled to electrospray ionization tandem mass
      spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry to elucidate the full identity of these ladderane lipids. This
      revealed a wide variety of ladderane lipid species with either a phosphocholine
      or phosphoethanolamine polar headgroup attached to the glycerol backbone. In
      addition, in silico analysis of genome data gained insight into the machinery for
      the biosynthesis of the phosphocholine and phosphoethanolamine phospholipids in
      anammox bacteria.

PMID- 16640589
TI  - The analysis of cell division and cell wall synthesis genes reveals mutationally
      inactivated ftsQ and mraY in a protoplast-type L-form of Escherichia coli.
AB  - Cell division and cell wall synthesis are tightly linked cellular processes for
      bacterial growth. A protoplast-type L-form Escherichia coli, strain LW1655F+,
      indicated that bacteria can divide without assembling a cell wall. However, the
      molecular basis of its phenotype remained unknown. To establish a first phenotype
      genotype correlation, we analyzed its dcw locus, and other genes involved in
      division of E. coli. The analysis revealed defective ftsQ and mraY genes,
      truncated by a nonsense and a frame-shift mutation, respectively. Missense
      mutations were determined in the ftsA and ftsW products yielding amino-acid
      replacements at conserved positions. FtsQ and MraY, obviously nonfunctional in
      the L-form, are essential for cell division and cell wall synthesis,
      respectively, in all bacteria with a peptidoglycan-based cell wall. LW1655F+ is
      able to survive their loss-of-functions. This points to compensatory mechanisms
      for cell division in the absence of murein sacculus formation. Hence, this L-form
      represents an interesting model to investigate the plasticity of cell division in
      E. coli, and to demonstrate how concepts fundamental for bacterial life can be
      bypassed.

PMID- 16640590
TI  - Direct inhibition of cytochrome c-induced caspase activation in vitro by
      Toxoplasma gondii reveals novel mechanisms of interference with host cell
      apoptosis.
AB  - The intracellular parasite Toxoplasma gondii is known to inhibit apoptosis of its
      host cell. The molecular mechanisms of this interference are, however, not yet
      completely understood. We show here that viable parasites prominently inhibited
      the activation of caspase 3/7 induced by cytochrome c, dATP and dithiothreitol in
      cytosolic extracts of human-derived Jurkat leukemic T cells. In contrast,
      granzyme B-induced caspase activity was only slightly diminished. De novo protein
      biosynthesis by T. gondii was dispensable for the inhibition of cytochrome c
      induced caspase activation. Furthermore, a complete parasite lysate or, more
      importantly, molecules released by extracellular parasites mediated the
      interaction with the caspase cascade. The cell-free system applied here is thus a
      valuable tool to study the interaction of T. gondii and possibly other
      intracellular pathogens with host cell apoptosis.

PMID- 16640592
TI  - Regulation of secondary metabolism by the carbon-nitrogen status in tobacco:
      nitrate inhibits large sectors of phenylpropanoid metabolism.
AB  - Interactions between nitrogen and carbon metabolism modulate many aspects of the
      metabolism, physiology and development of plants. This paper investigates the
      contribution of nitrate and nitrogen metabolism to the regulation of
      phenylpropanoid and nicotine synthesis. Wild-type tobacco was grown on 12 or 0.2
      mm nitrate and compared with a nitrate reductase-deficient mutant [Nia30(145)]
      growing on 12 mm nitrate. Nitrate-deficient wild-type plants accumulate high
      levels of a range of phenylpropanoids including chlorogenic acid, contain high
      levels of rutin, are highly lignified, but contain less nicotine than nitrogen
      replete wild-type tobacco. Nia30(145) resembles nitrate-deficient wild-type
      plants with respect to the levels of amino acids, but accumulates large amounts
      of nitrate. The levels of phenylpropanoids, rutin and lignin resemble those in
      nitrogen-replete wild-type plants, whereas the level of nicotine resembles that
      in nitrate-deficient wild-type plants. Expression arrays and real time RT-PCR
      revealed that a set of genes required for phenylpropanoid metabolism including
      PAL, 4CL and HQT are induced in nitrogen-deficient wild-type plants but not in
      Nia30(145). It is concluded that nitrogen deficiency leads to a marked shift from
      the nitrogen-containing alkaloid nicotine to carbon-rich phenylpropanoids. The
      stimulation of phenylpropanoid metabolism is triggered by changes of nitrate,
      rather than downstream nitrogen metabolites, and is mediated by induction of a
      set of enzymes in the early steps of the phenylpropanoid biosynthetic pathway.

PMID- 16640593
TI  - Arabidopsis myrosinases TGG1 and TGG2 have redundant function in glucosinolate
      breakdown and insect defense.
AB  - In Arabidopsis and other Brassicaceae, the enzyme myrosinase (beta-thioglucoside
      glucohydrolase, TGG) degrades glucosinolates to produce toxins that deter
      herbivory. A broadly applicable selection for meiotic recombination between
      tightly linked T-DNA insertions was developed to generate Arabidopsis tgg1tgg2
      double mutants and study myrosinase function. Glucosinolate breakdown in crushed
      leaves of tgg1 or tgg2 single mutants was comparable to that of wild-type,
      indicating redundant enzyme function. In contrast, leaf extracts of tgg1tgg2
      double mutants had undetectable myrosinase activity in vitro, and damage-induced
      breakdown of endogenous glucosinolates was apparently absent for aliphatic and
      greatly slowed for indole glucosinolates. Maturing leaves of myrosinase mutants
      had significantly increased glucosinolate levels. However, developmental
      decreases in glucosinolate content during senescence and germination were
      unaffected, showing that these processes occur independently of TGG1 and TGG2.
      Insect herbivores with different host plant preferences and feeding styles varied
      in their responses to myrosinase mutations. Weight gain of two Lepidoptera, the
      generalist Trichoplusia ni and the facultative Solanaceae-specialist Manduca
      sexta, was significantly increased on tgg1tgg2 double mutants. Two crucifer
      specialist Lepidoptera had differing responses. Whereas Plutella xylostella was
      unaffected by myrosinase mutations, Pieris rapae performed better on wild-type,
      perhaps due to reduced feeding stimulants in tgg1tgg2 mutants. Reproduction of
      two Homoptera, Myzus persicae and Brevicoryne brassicae, was unaffected by
      myrosinase mutations.

PMID- 16640594
TI  - A specific transporter for iron(III)-phytosiderophore in barley roots.
AB  - Iron acquisition of graminaceous plants is characterized by the synthesis and
      secretion of the iron-chelating phytosiderophore, mugineic acid (MA), and by a
      specific uptake system for iron(III)-phytosiderophore complexes. We identified a
      gene specifically encoding an iron-phytosiderophore transporter (HvYS1) in
      barley, which is the most tolerant species to iron deficiency among graminaceous
      plants. HvYS1 was predicted to encode a polypeptide of 678 amino acids and to
      have 72.7% identity with ZmYS1, a first protein identified as an iron(III)
      phytosiderophore transporter in maize. Real-time RT-PCR analysis showed that the
      HvYS1 gene was mainly expressed in the roots, and its expression was enhanced
      under iron deficiency. In situ hybridization analysis of iron-deficient barley
      roots revealed that the mRNA of HvYS1 was localized in epidermal root cells.
      Furthermore, immunohistological staining with anti-HvYS1 polyclonal antibody
      showed the same localization as the mRNA. HvYS1 functionally complemented yeast
      strains defective in iron uptake on media containing iron(III)-MA, but not iron
      nicotianamine (NA). Expression of HvYS1 in Xenopus oocytes showed strict
      specificity for both metals and ligands: HvYS1 transports only iron(III) chelated
      with phytosiderophore. The localization and substrate specificity of HvYS1 is
      different from those of ZmYS1, indicating that HvYS1 is a specific transporter
      for iron(III)-phytosiderophore involved in primary iron acquisition from soil in
      barley roots.

PMID- 16640595
TI  - A novel R2R3 MYB transcription factor NtMYBJS1 is a methyl jasmonate-dependent
      regulator of phenylpropanoid-conjugate biosynthesis in tobacco.
AB  - Target metabolic and large-scale transcriptomic analyses of tobacco (Nicotiana
      tabacum L.) Bright Yellow-2 (BY-2) cells were employed to identify novel gene(s)
      involved in methyl jasmonate (MJ)-dependent function in plants. At the metabolic
      level, we describe the specific accumulation of several phenylpropanoid-polyamine
      conjugates in MJ-treated BY-2 cells. Furthermore, global gene expression analysis
      of MJ-treated cells using a 16K cDNA microarray containing expressed sequence
      tags (ESTs) from BY-2 cells revealed 828 genes that were upregulated by MJ
      treatment within 48 h. Using time-course expression data we identified a novel MJ
      inducible R2R3 MYB-type transcription factor (NtMYBJS1) that was co-expressed in
      a close temporal pattern with the core phenylpropanoid genes phenylalanine
      ammonia-lyase (PAL) and 4-coumarate:CoA ligase (4CL). Overexpression of NtMYBJS1
      in tobacco BY-2 cells caused accumulation of specific phenylpropanoid conjugates
      in the cells. Subsequent microarray analysis of NtMYBJS1 transgenic lines
      revealed that a limited number of genes, including PAL and 4CL, were specifically
      induced in the presence of the NtMYBJS1 transgene. These results, together with
      results of both antisense expression analysis and of gel mobility shift assays,
      strongly indicate that the NtMYBJS1 protein functions in tobacco MJ signal
      transduction, inducing phenylpropanoid biosynthetic genes and the accumulation of
      phenylpropanoid-polyamine conjugates during stress.

PMID- 16640596
TI  - Direct regulation of the floral homeotic APETALA1 gene by APETALA3 and PISTILLATA
      in Arabidopsis.
AB  - The floral homeotic gene APETALA1 (AP1) specifies floral meristem identity and
      sepal and petal identity in Arabidopsis. Consistent with its multiple roles
      during floral development, AP1 is initially expressed throughout the floral
      meristem, and later its expression becomes restricted to sepal and petal
      primordia. Using chromatin immunoprecipitation, we show that the floral homeotic
      PISTILLATA (PI) protein, required for petal and stamen development, has the
      ability to bind directly to the promoter region of AP1. In support of the
      hypothesis that PI, and its interacting partner APETALA3 (AP3), regulates the
      transcription of AP1, we show that AP1 transcript levels are elevated in strong
      ap3-3 mutant plants. Kinetic studies, using transgenic Arabidopsis plants in
      which both AP3 and PI are under post-translational control, show that AP1
      transcript levels are down regulated within 2 h of AP3/PI activation. This
      implies that the reduction in AP1 transcripts is an early event in the cascade
      following AP3/PI induction and provides independent support for the hypothesis
      that AP1 is a direct target of the AP3/PI heterodimer. Together these results
      suggest a model whereby AP3/PI directly acts, in combination with other factors,
      to restrict the expression of AP1 during early stages of floral development.

PMID- 16640597
TI  - AtNAP, a NAC family transcription factor, has an important role in leaf
      senescence.
AB  - Leaf senescence is a unique developmental process that is characterized by
      massive programmed cell death and nutrient recycling. The underlying molecular
      regulatory mechanisms are not well understood. Here we report the functional
      analysis of AtNAP, a gene encoding a NAC family transcription factor. Expression
      of this gene is closely associated with the senescence process of Arabidopsis
      rosette leaves. Leaf senescence in two T-DNA insertion lines of this gene is
      significantly delayed. The T-DNA knockout plants are otherwise normal. The mutant
      phenotype can be restored to wild-type by the intact AtNAP, as well as by its
      homologs in rice and kidney bean plants that are also upregulated during leaf
      senescence. Furthermore, inducible overexpression of AtNAP causes precocious
      senescence. These data strongly suggest that AtNAP and its homologs play an
      important role in leaf senescence in Arabidopsis and possibly in other plant
      species.

PMID- 16640598
TI  - Genome-wide analysis of high-altitude maize and gene knockdown stocks implicates
      chromatin remodeling proteins in response to UV-B.
AB  - A comparative analysis, by expression profiling of maize, was performed to
      identify novel components in the mechanisms of maize responses to UV-B. Five high
      altitude landraces grown from 2,000 to 3,400 m naturally receive higher UV-B
      fluence than plants at lower altitudes and similar latitudes. These high-altitude
      landraces were compared directly with a low-altitude line and with literature
      reports for other temperate maize lines. A microarray analysis demonstrated that
      among the UV-B responsive transcripts, several types of gene implicated in
      chromatin remodeling are differentially expressed before and after UV-B treatment
      in high-altitude lines. RNAi transgenic plants with lower expression of four such
      chromatin-associated genes exhibited hypersensitivity to UV-B by measurements of
      leaf arching, increased leaf chlorosis and necrosis, and altered UV-B regulation
      of selected genes. These results collectively suggest that genes involved in
      chromatin remodeling are crucial for UV-B acclimation and that some high-altitude
      lines exhibit adaptations to this challenge.

PMID- 16640599
TI  - Transitions in the functioning of the shoot apical meristem in birch (Betula
      pendula) involve ethylene.
AB  - In many trees, a short photoperiod (SD) triggers substantial physiological
      adjustments necessary for over-wintering. We have used transgenic ethylene
      insensitive birches (Betula pendula), which express the Arabidopsis ethylene
      receptor gene ETR1 carrying the dominant mutation etr1-1, to investigate the role
      of ethylene in SD-induced responses in the shoot apical meristem (SAM). Under SD,
      the ethylene-insensitive trees ceased elongation growth comparably to the wild
      type. In contrast, the formation of terminal buds, which in trees is typically
      induced by SD, was abolished. However, although delayed, endo-dormancy did
      eventually develop in the ethylene-insensitive trees. This, together with the
      rapid resumption of growth in the ethylene-insensitive trees after transfer from
      non-permissive to permissive conditions suggests that ethylene facilitates the SD
      induced terminal bud formation, as well as growth arrest. In addition, apical
      buds of the ethylene-insensitive birch did not accumulate abscisic acid (ABA)
      under SD, suggesting interaction between ethylene and ABA signalling in the bud.
      Alterations in SAM functioning were further exemplified by reduced apical
      dominance and early flowering in ethylene-insensitive birches. Gene expression
      analysis of shoot apices revealed that the ethylene-insensitive birch lacked the
      marked increase in expression of a beta-xylosidase gene typical to the SD-exposed
      wild-type. The ethylene-dependent beta-xylosidase gene expression is hypothesized
      to relate to modification of cell walls in terminal buds during SD-induced growth
      cessation. Our results suggest that ethylene is involved in terminal bud
      formation and in the timely suppression of SAM activity, not only in the shoot
      apex, but also in axillary and reproductive meristems.

PMID- 16640600
TI  - Phytochrome-mediated agravitropism in Arabidopsis hypocotyls requires GIL1 and
      confers a fitness advantage.
AB  - Plants use specialized photoreceptors to detect the amount, quality, periodicity
      and direction of light and to modulate their growth and development accordingly.
      These regulatory light signals often interact with other environmental cues.
      Exposure of etiolated Arabidopsis seedlings to red (R) or far-red (FR) light
      causes hypocotyls to grow in random orientations with respect to the
      gravitational vector, thus overcoming the signal from gravity to grow upwards.
      This light response, mediated by either phytochrome A or phytochrome B,
      represents a prime example of cross-talk between environmental signalling
      systems. Here, we report the isolation the mutant gil1 (for gravitropic in the
      light) in which hypocotyls continue to grow upwards after exposure of seedlings
      to R or FR light. The gil1 mutant displays no other phenotypic alterations in
      response to gravity or light. Cloning of GIL1 has identified a novel gene that is
      necessary for light-dependent randomization of hypocotyl growth orientation.
      Using gil1, we have demonstrated that phytochrome-mediated randomization of
      Arabidopsis hypocotyl orientation provides a fitness advantage to seedlings
      developing in patchy, low-light environments.

PMID- 16640601
TI  - AtCHIP functions as an E3 ubiquitin ligase of protein phosphatase 2A subunits and
      alters plant response to abscisic acid treatment.
AB  - CHIP proteins are E3 ubiquitin ligases that promote degradation of Hsp70 and
      Hsp90 substrate proteins through the 26S proteasome in animal systems. A CHIP
      like protein in Arabidopsis, AtCHIP, also has E3 ubiquitin ligase activity and
      has important roles to play under conditions of abiotic stress. In an effort to
      study the mode of action of AtCHIP in plant cells, proteins that physically
      interact with it were identified. Like its animal orthologs, AtCHIP interacts
      with a unique class of ubiquitin-conjugating enzymes (UBC or E2) that belongs to
      the stress-inducible UBC4/5 class in yeast. AtCHIP also interacts with other
      proteins, including an A subunit of protein phosphatase 2A (PP2A). This PP2A
      subunit appears to be a substrate of AtCHIP, because it can be ubiquitylated by
      AtCHIP in vitro and because the activity of PP2A is increased in AtCHIP
      overexpressing plants in the dark or under low-temperature conditions. Unlike the
      rcn1 mutant, that has reduced PP2A activity due to a mutation in one of the A
      subunit genes of PP2A, AtCHIP-overexpressing plants are more sensitive to ABA
      treatment. Since PP2A was previously shown to be involved in low-temperature
      responses in plants, the low-temperature-sensitive phenotype observed in AtCHIP
      overexpressing plants might be partly due to the change in PP2A activity. These
      data suggest that the E3 ubiquitin ligase AtCHIP may function upstream of PP2A in
      stress-responsive signal transduction pathways under conditions of low
      temperature or in the dark.

PMID- 16640602
TI  - Prohibitin is involved in mitochondrial biogenesis in plants.
AB  - Prohibitin, which consists of two subunits PHB1 and PHB2, plays a role in cell
      cycle progression, senescence, apoptosis, and maintenance of mitochondrial
      function in mammals and yeast. In this study, we examined the role of prohibitins
      in plants by using virus-induced gene silencing (VIGS) of two prohibitin subunit
      genes of Nicotiana benthamiana, designated NbPHB1 and NbPHB2. NbPHB1 and NbPHB2
      were targeted to the mitochondria, and their gene expression was suppressed
      during senescence. VIGS of NbPHB2 caused severe growth inhibition, leaf yellowing
      and symptoms of cell death, whereas VIGS of NbPHB1 resulted in a milder
      phenotype. At the cellular level, depletion of these subunits affected
      mitochondria by severely reducing their number and/or mass, and by causing
      morphological and physiological abnormalities. Suppression of prohibitin function
      resulted in a 10- to 20-fold higher production of reactive oxygen species and
      induced premature leaf senescence. Finally, disruption of prohibitin function
      rendered the plants more susceptible to various oxidative stress-inducing
      reagents, including H(2)O(2), paraquat, antimycin A and salicylic acid. These
      results suggest that prohibitins play a crucial role in mitochondrial biogenesis
      and protection against stress and senescence in plant cells.

PMID- 16640603
TI  - A transglucosidase necessary for starch degradation and maltose metabolism in
      leaves at night acts on cytosolic heteroglycans (SHG).
AB  - The recently characterized cytosolic transglucosidase DPE2 (EC 2.4.1.25) is
      essential for the cytosolic metabolism of maltose, an intermediate on the pathway
      by which starch is converted to sucrose at night. In in vitro assays, the enzyme
      utilizes glycogen as a glucosyl acceptor but the in vivo acceptor molecules
      remained unknown. In this communication we present evidence that DPE2 acts on the
      recently identified cytosolic water-soluble heteroglycans (SHG) as does the
      cytosolic phosphorylase (EC 2.4.1.1) isoform. By using in vitro two-step (14)C
      labeling assays we demonstrate that the two transferases can utilize the same
      acceptor sites of the SHG. Cytosolic heteroglycans from a DPE2-deficient
      Arabidopsis mutant were characterized. Compared with the wild type the glucose
      content of the heteroglycans was increased. Most of the additional glucosyl
      residues were found in the outer chains of SHG that are released by an endo-alpha
      arabinanase (EC 3.2.1.99). Additional starch-related mutants were characterized
      for further analysis of the increased glucosyl content. Based on these data, the
      cytosolic metabolism of starch-derived carbohydrates is discussed.

PMID- 16640604
TI  - The N-terminal ATPase AT-hook-containing region of the Arabidopsis chromatin
      remodeling protein SPLAYED is sufficient for biological activity.
AB  - The SNF2-like chromatin-remodeling ATPase SPLAYED (SYD) was identified as a co
      activator of floral homeotic gene expression in Arabidopsis. SYD is also required
      for meristem maintenance and regulates flowering under a non-inductive
      photoperiod. SNF2 ATPases are structurally and functionally conserved from yeast
      to humans. In addition to the conserved protein features, SYD has a large unique
      C-terminal domain. We show here that SYD is present as two forms in the nucleus,
      full-length and truncated, with the latter apparently lacking the C-terminal
      domain. The ratio of the two forms of endogenous SYD differs in juvenile and in
      adult tissues. Furthermore, an SYD variant lacking the C-terminal domain
      (SYDDeltaC) rescues the syd null mutant, indicating that the N-terminal ATPase AT
      hook-containing region of SYD is sufficient for biological activity. Plants
      expressing SYDDeltaC show molecular and morphological phenotypes opposite to
      those of the null mutant, suggesting that the construct results in increased
      activity. This increased activity is at least in part due to elevated SYD protein
      levels in these lines. We propose that the C-terminal domain may control SYD
      accumulation and/or specific activity in the context of the full-length protein.
      The presence of the C-terminal domain in rice SYD suggests that its role is
      probably conserved in the two classes of flowering plants.

PMID- 16640605
TI  - Hybrid transcription system for controlled plastid transgene expression.
AB  - Plastid transformation technologies have developed rapidly over the last few
      years, reflecting their value in the study of the principal mechanisms of plastid
      gene expression and commercial interest in using plastids as bioreactors.
      Application of this technology is still limited by the difficulty of obtaining
      regulated, selective expression of plastid transgenes. The plastid genome is
      transcribed by two different types of RNA polymerase. One of them is of the
      eubacterial type of polymerase, and its subunits are encoded in the plastid
      genome [plastid-encoded RNA polymerase (PEP)]. The other one is of the phage type
      and nucleus-encoded [nucleus-encoded RNA polymerase (NEP)]. To obtain selective
      transgene expression, we have made use of the similarities and differences
      between the eubacterial and the plastid eubacterial type transcription systems.
      We created a hybrid transcription system in which the transgene is placed under
      the control of a eubacterial promoter which does not exist in the plastid genome
      and which is not recognized by the plastid endogenous transcriptional machinery.
      Selective transcription of the transgene is achieved by the supply of a chimeric
      transcription factor that interacts with PEP and directs it specifically to the
      foreign eubacterial-type transgene promoter. This hybrid transcription system
      could be used for biotechnological and fundamental research applications as well
      as in the characterization of the evolutionary differences between the
      eubacterial and the plastid eubacterial-type transcription systems.

PMID- 16640606
TI  - Membrane-associated transcripts in Arabidopsis; their isolation and
      characterization by DNA microarray analysis and bioinformatics.
AB  - Membrane-associated, integral membrane and secreted proteins are of key
      importance in many cellular processes. For most of the 28,952 predicted proteins
      in Arabidopsis, the actual subcellular localization has not been demonstrated
      experimentally. So far, their potential membrane-association has been deduced
      from algorithms that predict transmembrane domains and signal peptides. However,
      the comprehensiveness and accuracy of these algorithms is still limited. The
      majority of membrane-associated and secreted proteins is synthesized on membrane
      bound polysomes. Therefore, the isolation and characterization of mRNA associated
      with membrane-bound polysomes offers an experimental tool for the genome-wide
      identification of these proteins. Here we describe an efficient method to isolate
      mRNA from membrane-bound polysomes and report on the validation of the method to
      enrich for transcripts encoding membrane-associated and secreted proteins. The
      sensitivity and reproducibility of the isolation method was investigated by DNA
      microarray analysis. Pearson correlations between transcript levels obtained from
      three replicate isolations showed that the method is highly reproducible. A
      significant enrichment for mRNAs encoding proteins containing predicted
      transmembrane domains and signal peptides was observed in the membrane-bound
      polysomal fraction. In this fraction, 301 transcripts were classified by gene
      ontologies as 'cellular component unknown', and potentially encode previously
      unrecognized secreted or membrane-associated proteins.

PMID- 16640607
TI  - Editorial: health of nomadic pastoralists: new approaches towards equity
      effectiveness.

PMID- 16640608
TI  - Comparative efficacy of chloroquine and sulphadoxine--pyrimethamine in pregnant
      women and children: a meta-analysis.
AB  - OBJECTIVE: To compare the efficacy of chloroquine and sulphadoxine-pyremethamine
      against Plasmodium falciparum infection in pregnant women and in children from
      the same endemic areas of Africa, with the aim of determining the level of
      correspondence in efficacy determinations in these two risk groups. METHODS: Meta
      analysis of nine published and unpublished in vivo antimalarial efficacy studies
      in pregnant women and in children across five African countries. RESULTS:
      Pregnant women (all gravidae) were more likely to be sensitive than children to
      both chloroquine (odds ratio: 2.07; 95% confidence interval: 1.5, 2.9) and
      sulphadoxine-pyrimethamine (odds ratio: 2.66; 95% confidence interval: 11.1,
      6.7). Pregnant women demonstrated an almost uniform increased sensitivity for
      peripheral parasite clearance at day 14 compared with children. This finding was
      consistent across a wide range of drug sensitivities. Primigravidae at day 14
      showed lower clearance to antimalarial drugs than multigravidae (P<0.05). There
      was no significant difference between parasite clearance in primigravidae and in
      children. CONCLUSION: The greater drug sensitivity in pregnant women probably
      indicates differences in host susceptibility rather than parasite resistance.
      Parasite sensitivity patterns in children may be a suitable guide to antimalarial
      policy in pregnant women.

PMID- 16640609
TI  - Urban malaria and anaemia in children: a cross-sectional survey in two cities of
      Ghana.
AB  - OBJECTIVE: To describe the epidemiology of urban malaria, an emerging problem in
      sub-Saharan Africa. METHOD: Cross-sectional surveys of communities in Accra and
      Kumasi, Ghana, determining risk factors for malaria infection and anaemia in
      children aged 6-60 months. RESULTS: Malaria prevalence rates ranged from 2% to
      33% between urban communities. 47.1% of children were anaemic (Hb<11.0 g/dl).
      Factors associated with malaria prevalence were low socio-economic status, age
      and anaemia. The attributable risks of anaemia and severe anaemia (Hb<8.0 g/dl)
      caused by malaria were 5% and 23% respectively. CONCLUSIONS: Malaria in urban
      areas displayed a heterogeneity and complexity that differed from the rural
      environment, which has important implications for malaria control. Marked intra
      city variation indicates the importance of targeting specific areas or districts.
      The most vulnerable group, the urban poor, should be prioritized when designing
      control measures. This would require careful assessment of the malaria risk
      pattern in any city to guide an integrated control program.

PMID- 16640610
TI  - Tolerability of amodiaquine and sulphadoxine-pyrimethamine, alone or in
      combination for the treatment of uncomplicated Plasmodium falciparum malaria in
      Rwandan adults.
AB  - OBJECTIVE: To assess the tolerability and efficacy of amodiaquine
      (AQ)+sulphadoxine-pyrimethamine (SP), the first-line malaria treatment in Rwanda.
      METHOD: Randomized, double-blind trial in 2003 in Kigali town. A total of 351
      adult patients with uncomplicated Plasmodium falciparum malaria were randomly
      allocated to one of the following treatments: AQ+SP, AQ or SP. We followed
      patients until day 14 after treatment and recorded adverse events (AEs) and
      clinical and parasitological outcomes. RESULTS: One hundred and eighteen patients
      reported at least one AE: 40% in the AQ, 39% in the AQ+SP and 21% in the SP
      groups. The AE was classified as possibly related to the antimalarial treatment
      for 86 patients. The Risk Ratio for at least one AE after treatment was
      significantly and about fourfold higher in patients receiving AQ or AQ+SP than in
      patients receiving SP. Pruritus and fatigue were significantly more frequent in
      patients treated with AQ or AQ+SP than in those receiving SP. Severe AEs, such as
      fatigue, nausea, dizziness and vomiting, were observed in four patients treated
      with AQ, in 10 treated with AQ+SP and in one patient treated with SP. CONCLUSION:
      Amodiaquine+SP is not well tolerated and a substantial proportion of patients
      experienced pruritus and fatigue, thus decreasing their compliance and
      compromising the first line treatment implementation at national level. This
      renders AQ-containing regimens sub-optimal; better-tolerated treatments should be
      identified.

PMID- 16640611
TI  - The indoor use of plastic sheeting pre-impregnated with insecticide for control
      of malaria vectors.
AB  - OBJECTIVE: To evaluate the efficacy of permethrin-treated plastic sheeting (ITPS)
      applied as a lining to the ceiling or walls of rooms against pyrethroid
      susceptible and pyrethroid-resistant Anopheles gambiae. METHOD: Overnight tests
      were carried out in veranda-trap experimental huts in Vallee du Kou, where two
      molecular forms of A. gambiae, S and M, occur. The S form is mostly pyrethroid
      resistant due to the kdr mechanism, and the M form is mostly kdr susceptible. A
      variety of ITPS covered surfaces were tested, ranging from ceiling only to all
      walls plus ceiling covered. RESULTS: ITPS had a major effect on the mortality of
      mosquitoes, the proportion killed being dependent upon the surface area covered.
      Homozygotes for kdr resistance showed lower rates of mortality than did
      heterozygotes or homozygotes for susceptibility. Deterred entry of mosquitoes and
      inhibition of blood feeding were also correlated with surface area covered. The
      mode of action and efficacy of ITPS seems to bear closer resemblance to that
      induced by indoor residual spraying (IRS) than to that induced by insecticide
      treated nets. CONCLUSIONS: ITPS might be conceived as being equivalent to long
      lasting or permanent IRS but without some of the operational constraints normally
      associated with spraying. High coverage of ITPS could potentially have a mass
      population effect on mosquitoes and give rise to long-term community protection
      against malaria. A phase III trial is justified to assess the acceptability of
      ITPS and its efficacy against malaria.

PMID- 16640612
TI  - The efficacy of sulfadoxine-pyrimethamine alone and in combination with
      chloroquine for malaria treatment in rural Eastern Sudan: the interrelation
      between resistance, age and gametocytogenesis.
AB  - OBJECTIVE: To compare the efficacy of sulfadoxine-pyremethamine (SP)+chloroquine
      (CQ) combination treatment against falciparum malaria with SP treatment alone.
      METHOD: In-vivo study of 254 patients with uncomplicated Plasmodium falciparum
      malaria in rural eastern Sudan, where the population is semi-immune. RESULTS:
      Sulfadoxine-pyremethamine treatment alone cured 68.3% (41/60) and SP+CQ cured
      63.4% (123/194). Early and late treatment failures occurred in both treatment
      groups. Host age (as a marker for immunity) and parasite gametocytogenesis (as a
      marker for transmissibility) were significantly associated with SP resistance.
      Patients who were cured were significantly older (median age 21 years) than
      patients whose treatment failed (median age 12 years). Gametocyte production was
      significantly higher in patients with treatment failure (0.72 vs 0.45) and
      associated with younger age. Gametocyte counts were comparable between both
      groups until day 7 of follow up; thereafter, they were significantly higher in
      patients with treatment failure. However, the longevity of gametocytes was
      comparable in both treatment groups. CONCLUSION: Chloroquine did not improve the
      parasite response to SP. Age was strongly associated with clearance of SP
      resistant parasites. The fast rise of SP resistance may partially be due to
      selection of SP resistant parasites and expansion of the resistant population
      through the gametocytogenic effect of SP.

PMID- 16640613
TI  - Seasonal variation and high multiplicity of first Plasmodium falciparum
      infections in children from a holoendemic area in Ghana, West Africa.
AB  - OBJECTIVE: To assess the prevalence and multiplicity of Plasmodium falciparum
      infections in Ghanaian infants. METHOD: In an epidemiological study in an area
      holoendemic for malaria in Ghana, the prevalence and multiplicity of P.
      falciparum infections (MOI) were assessed in 1069 three month-old infants by
      typing of the genes encoding the merozoite surface proteins 1 and 2 (msp-1, msp
      2) over a recruitment period of one year. Alleles were amplified using allele
      family-specific polymerase chain reaction (PCR) assays and determined according
      to their length polymorphisms on a genetic analyzer. RESULTS: The occurrence of
      early infections was dependent on the season (month-stratified prevalence 6.4
      29.0%). Diversity of msp-alleles was extensive and significantly higher in the
      dry than in the rainy season. CONCLUSIONS: The level of infection prevalence and
      the high multiplicity of infections (median 4, maximum 14 strains per isolate) in
      the first months of life indicate early contacts with parasites exhibiting a wide
      repertoire of antigens and, most likely, multiple infections per single mosquito
      bite.

PMID- 16640614
TI  - Detection of trypanosome-specific antibodies in saliva, towards non-invasive
      serological diagnosis of sleeping sickness.
AB  - OBJECTIVE: The detection of trypanosome-specific antibodies in saliva is
      technically feasible, and, if clinically validated, could become an attractive
      option for non-invasive diagnosis of sleeping sickness. We wanted to optimize the
      test format of an enzyme-linked immunosorbent assay (ELISA)-based antibody
      detection system. METHODS: Different ELISA formats for antibody detection in
      serum and saliva were developed and standardized. Saliva and serum samples were
      collected from 78 patient and 128 endemic control samples, and sensitivity and
      specificity of saliva ELISAs, serum ELISAs and the card agglutination test for
      trypanosomiasis (CATT), were evaluated. RESULTS: All ELISA formats showed
      sensitivity and specificity above 90%. Saliva ELISAs showed a similar test
      performance as serum ELISAs and the CATT on whole blood or serum. CONCLUSIONS:
      This study confirms the potential of trypanosome-specific antibody detection in
      saliva.

PMID- 16640615
TI  - Are maternal re-infections with Trypanosoma cruzi associated with higher
      morbidity and mortality of congenital Chagas disease?
AB  - BACKGROUND: Comparing two surveys performed in Bolivia in 1992-1994 and 1999
      2001, we reported a significant decrease in the proportions of severe and mortal
      forms of congenital Chagas disease. This might be due to a reduction of vectorial
      density (VD) in maternal residence area, raising the question of a possible
      causal relationship between such VD, maternal parasitaemia and prognosis of
      congenital infection with Trypanosoma cruzi. METHOD: Comparisons of
      haematological and parasitological data obtained from Bolivian mothers infected
      with T. cruzi, and of clinical and biological data obtained from their infected
      and uninfected newborns, stratified according to VD in the area of maternal
      residence. RESULTS: i) Blood hematocrit rates or hemoglobin amounts were within
      the normal ranges and similar in all the maternal groups, whatever the VD in
      their areas of residence; ii) mothers living in high VD areas displayed a higher
      frequency of hemocultures positive for T. cruzi; iii) newborns congenitally
      infected with T. cruzi, but not uninfected babies born from infected mothers,
      displayed higher frequencies of very low Apgar scores, low birth weights,
      prematurity, respiratory distress syndrome or anasarca, as well as higher
      mortality rates when their mothers lived in areas of high VD. CONCLUSION:
      Frequent bites of blood sucking Reduvidae during pregnancy do not induce maternal
      anaemia, but, likely through multiple maternal re-infections with T. cruzi,
      increase maternal parasitemia and worsen congenital Chagas disease. Maternal
      dwelling in areas of high VD is associated with a serious increased risk of
      severe and mortal congenital Chagas disease.

PMID- 16640616
TI  - The elimination of Trypanosoma brucei gambiense sleeping sickness in the focus of
      Luba, Bioko Island, Equatorial Guinea.
AB  - After the resurgence of sleeping sickness in Luba, Equatorial Guinea, a major
      campaign to control the disease was established in 1985. The campaign comprised
      no vector control, but intensive active and passive surveillance using serology
      for screening, and treatment of all parasitological and suspected serological
      cases. Total prevalence was used to classify villages as endemic, at risk,
      anecdotal and non-endemic which also allowed defining the geographic extent of
      the focus. Active case-finding was implemented from 1985 to 2004. The frequency
      of surveys was based on parasitological prevalence: twice a year during
      intensified control, once a year during ordinary control and once every 2 years
      during the control consolidation phase, when the parasitological prevalence in
      the whole focus fell to 0.1%. From 1985 to 1999, the indirect immunofluorescent
      antibody test (IFAT) was used as an initial screening tool, followed by
      parasitological confirmation of IFAT positive cases, and the Card Agglutination
      Trypanosomiasis Test (CATT) if necessary. In 2000, the IFAT was replaced by the
      CATT. Serum-positive individuals without parasitological confirmation were
      subsequently tested on serial dilution. All cases underwent lumbar puncture to
      determine the stage of the disease. First-stage cases were treated with
      pentamidine and second-stage cases with melarsoprol. A few relapses and very
      advanced cases were treated with eflornithine. The last sleeping sickness case
      was identified and treated in 1995.

PMID- 16640617
TI  - Comparison of cytokine plasma levels in human African trypanosomiasis.
AB  - BACKGROUND: Immunological studies suggest that human African trypanosomiasis
      (HAT) is associated with inflammatory responses. A better understanding of the
      complex cytokine interactions regulating HAT infections is essential to elucidate
      the mechanisms of generalized immunosuppression. METHOD: We determined levels of
      interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma protein levels in plasma samples from three groups of
      individuals from the Democratic Republic of Congo: (i) HAT cases; (ii)
      seropositive individuals for whom parasite detection was negative and (ii)
      controls. RESULTS: Plasma levels of six cytokines were significantly higher in
      HAT cases than in both controls (P<0.003) and seropositive individuals (P<0.016).
      IL-2 and IL-10 concentrations were significantly lower (P<0.02) in the
      seropositive group than in the control one. CONCLUSION: Human African
      trypanosomiasis leads to the development of strong cytokine responses, indicating
      the potential involvement of IL-2 and IL-10 in the phenomenon of seropositivity
      without parasitological confirmation. This strongly suggests the involvement of
      immunity in this particular aspect of HAT epidemiology.

PMID- 16640618
TI  - Management of mutual health organizations in Ghana.
AB  - OBJECTIVE: Mutual Health Organizations (MHO) emerged in Ghana in the mid-1990s.
      The organizational structure and financial management of private and public MHO
      hold important lessons for the development of national health insurance in Ghana,
      but there is little evidence to date on their features. This paper aims at
      filling this data gap, and at making recommendations to Ghanaian authorities on
      how to stimulate the success of MHO. METHODS: Survey among 45 private and public
      MHO in Ghana in 2004-2005, asking questions on their structure, financial
      management and financial position. RESULTS: Private MHO had more autonomy in
      setting premiums and benefit packages, and had higher community participation in
      meetings than public MHO. MHO in general had few measures in place to control
      moral hazard and reduce adverse selection, but more measures to control fraud and
      prevent cost escalation. The vast majority of schemes were managed by formally
      trained and paid staff. The financial results varied considerably. CONCLUSIONS:
      Ghanaian authorities regulate the newly established public MHO, but may do good
      by leaving them a certain level of autonomy in decision-making and secure
      community participation. The financial management of MHO is suboptimal, which
      indicates the need for technical assistance.

PMID- 16640619
TI  - The burden of disease in Zimbabwe in 1997 as measured by disability-adjusted life
      years lost.
AB  - OBJECTIVE: To rank health problems contributing most to the burden of disease in
      Zimbabwe using disability-adjusted life years as the population health measure.
      METHODS: Epidemiological information was derived from multiple sources.
      Population size and total number of deaths by age and sex for the year 1997 were
      taken from a nationwide census. The cause of death pattern was determined based
      on data from the Vital Registration System, which was adjusted for under
      reporting of human immunodeficiency virus (HIV) and reallocation of ill-defined
      causes. Non-fatal disease figures were estimated based on local disease
      registers, surveys and routine health service data supplemented by estimates from
      epidemiological studies from other settings if no Zimbabwean sources were
      available. Disease and public health experts were consulted about the
      identification of the best possible sources of information, the quality of these
      sources and data adjustments made. RESULTS: From the information collected, HIV
      infection emerged as the single most serious public health problem in Zimbabwe
      responsible for 49% of the total disease burden. A quarter of the total burden of
      disease was attributed to morbidity rather than premature mortality. The share of
      the disease burden was similar in females and males. CONCLUSION: Using local
      sources of information to a large extent, it was possible to develop plausible
      estimates of the size and the relative significance of the major health problems
      in Zimbabwe. The disease pattern of Zimbabwe differed substantially from regional
      estimates for sub-Saharan Africa justifying the need for countries to develop
      their own burden of disease estimates.

PMID- 16640620
TI  - [Emergency obstetrical care in Benin referral hospitals: 'near miss' patients'
      views].
AB  - OBJECTIVE: To evaluate emergency obstetric care and the perceptions and
      expectations of women who experienced 'near miss' events to improve maternal
      health in Benin. METHODS: Qualitative survey in seven hospitals at the three
      referral levels of the health pyramid from July to October 2003. We used two
      methods: 557 women with near miss events were interviewed in hospital and a
      standard questionnaire completed; then semi-structured individual interviews were
      conducted at home with 42 of these 557 women. RESULTS: Provided care,
      accommodation, facilities, costs and modalities of recovery, hygiene of the
      premises, dynamism, expertise, social support, behaviours and attitude of staff
      were the criteria used to express patients' satisfaction. Most women interviewed
      in hospital were happy with physical access, organization, functioning and
      environment. However, excessive costs and coercive recovery of the expenses,
      failure of the referral system, lack of empathy and discrimination of the nursing
      staff, lack of resources for emergencies, lack of hygiene and comfort of the
      premises were criticized by the women interviewed at home. CONCLUSION: The
      current maternal care system fails to effectively deal with obstetric
      complications. It needs to be better resourced, more easily available, cheaper
      and take into account the women's needs.

PMID- 16640621
TI  - Validity of verbal autopsy procedures for determining cause of death in Tanzania.
AB  - OBJECTIVES: To validate verbal autopsy (VA) procedures for use in sample vital
      registration. Verbal autopsy is an important method for deriving cause-specific
      mortality estimates where disease burdens are greatest and routine cause-specific
      mortality data do not exist. METHODS: Verbal autopsies and medical records (MR)
      were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal <5
      age group, and for ages of 5 years and over in Tanzania. Causes of death were
      assigned by physician panels using the International Classification of Disease,
      revision 10. Validity was measured by: cause-specific mortality fractions (CSMF);
      sensitivity; specificity and positive predictive value. Medical record diagnoses
      were scored for degree of uncertainty, and sensitivity and specificity adjusted.
      Criteria for evaluating VA performance in generating true proportional mortality
      were applied. RESULTS: Verbal autopsy produced accurate CSMFs for nine causes in
      different age groups: birth asphyxia; intrauterine complications; pneumonia;
      HIV/AIDS; malaria (adults); tuberculosis; cerebrovascular diseases; injuries and
      direct maternal causes. Results for 20 other causes approached the threshold for
      good performance. CONCLUSIONS: Verbal autopsy reliably estimated CSMFs for
      diseases of public health importance in all age groups. Further validation is
      needed to assess reasons for lack of positive results for some conditions.

PMID- 16640622
TI  - Post-abortion care and voluntary HIV counselling and testing--an example of
      integrating HIV prevention into reproductive health services.
AB  - OBJECTIVE: To assess the acceptance and outcome of voluntary HIV counselling and
      testing (VCT) among women who had an unsafe abortion. METHOD: 706 women were
      provided with post-abortion contraceptive service and offered VCT. We collected
      data on socioeconomic characteristics and contraceptive use and determined the
      HIV status of those who accepted VCT. Using a nested case-control design, we
      compared women who accepted HIV testing with women who did not. To study the
      association between socioeconomic factors, HIV testing acceptance and condom use
      in more detail, we did stratified analyses based on age and marital status.
      RESULTS: 58% of the women who had an unsafe abortion accepted HIV testing. Women
      who earned an income were more likely to accept testing than housewives. Women
      who accepted testing were more likely to accept using a condom. The HIV
      prevalence rate was 19% among single women aged 20-24 years and 25% among single
      women aged 25-45 years. CONCLUSION: HIV testing and condoms were accepted by most
      women who had an unsafe abortion. The poor reproductive health of these women
      could be improved by good post-abortion care that includes contraceptive
      counselling, VCT and condom promotion.

PMID- 16640623
TI  - No difference in HIV incidence and sexual behaviour between out-migrants and
      residents in rural Manicaland, Zimbabwe.
AB  - OBJECTIVES: Migration is associated with HIV infection, but the relationship has
      been mostly assessed in cross-sectional studies. In a prospective study, we
      investigated whether out-migrants are a selection of high-risk individuals and
      whether rural-to-urban migration results in risky sexual behaviour for HIV
      incidence. METHODS: A population cohort was enrolled in a stratified household
      census in four different community types in Manicaland, east Zimbabwe, between
      July 1998 and February 2000, and followed-up after 3 years. Out-migrants to the
      national capital (Harare), the provincial capital (Mutare) and other study areas
      were followed-up. A structured questionnaire was administered and an HIV test was
      conducted at each interview. HIV prevalence and sexual risk behaviour at
      baseline, and HIV incidence and sexual behaviour during follow-up were compared
      for out-migrants and residents. RESULTS: At baseline, future migrants were
      significantly younger, better educated and more likely to be single than
      residents. For males, migration was highest from subsistence farming areas and
      roadside trading centres and lowest from estates. After adjusting for age,
      education, marital status and location, there were no differences in HIV
      prevalence and sexual risk behaviour between future migrants and residents at
      baseline, for either sex. No significant differences in HIV incidence or sexual
      behaviour during follow-up were detected between rural-to-urban out-migrants and
      residents. CONCLUSIONS: Out-migrants from rural Zimbabwe did not have higher
      levels of HIV infection or sexual risk behaviour than residents either before or
      after they moved. These findings may be related to the mature stage of the HIV
      epidemic and the social and living conditions of migrants in Zimbabwean cities.

PMID- 16640624
TI  - Impact of chronic lymphatic filariasis on quantity and quality of productive work
      among weavers in an endemic village from India.
AB  - OBJECTIVE: To assess the impact of hydrocele and lymphoedema on the quantity and
      quality of productive work of weavers. METHOD: Case-control study in an endemic
      village in Andhra Pradesh, India. We collected qualitative data on work
      activities from cases and age- and sex-matched controls through informal
      discussions and observation. RESULTS: The mean (+/-standard deviation) daily work
      time of cases was 7.38 h (+/-2.47), significantly less than that of controls
      (8.17+/-2.41 h). Lost work time was equivalent to around 29 days of work in a
      year. Gender had significant influence on the mean number of working hours in
      this occupational group. Most cases could not weave, which is physically
      demanding, and preferred less strenuous tasks such as spinning, starching, dyeing
      or sizing. Hard physical labour constitutes 71.5% of total work time among
      patients and 83.7% in controls. As income also depends on the type of work, cases
      earn less. CONCLUSIONS: Filariasis has an adverse impact on the productivity of
      weavers, and morbidity management strategies and control programmes need to take
      this into account.

PMID- 16640625
TI  - Model-based analysis of trial data: microfilaria and worm-productivity loss after
      diethylcarbamazine-albendazole or ivermectin-albendazole combination therapy
      against Wuchereria bancrofti.
AB  - OBJECTIVES: To determine the efficacies of combinations of ivermectin or
      diethylcarbamazine and albendazole, which are recommended for use in mass
      treatment programmes against lymphatic filariasis. METHOD: Review of published
      trends in microfilarial (mf) intensities after treatment with these combination
      therapies. By fitting a mathematical model of treatment effects to the trial
      data, we quantified the efficacy of treatment, distinguishing between the killing
      of mf (mf loss) and a reduction in mf production by adult worms (worm
      productivity loss). After diethylcarbamazine-albendazole treatment mf density
      dropped immediately, then slowly but steadily decreased further (four trials).
      After ivermectin-albendazole treatment, mf densities immediately dropped to near
      zero levels, followed by a small increase (five trials). For diethylcarbamazine
      albendazole treatment the average mf loss was approximately 83% (ranging from 54%
      to 100% in the different studies) and worm-productivity loss was 100% (in all
      studies). For ivermectin-albendazole treatment, average mf loss was 100% (ranging
      from 98% to 100%) and worm productivity loss was 96% (ranging from 83% to 100%).
      The effects were dose-dependent. Sensitivity analysis showed that the estimates
      did not depend on assumptions on worm lifespan or premature period and little on
      assumptions on mf lifespan. CONCLUSION: The two therapies differ with respect to
      their direct effect on mf, but both are highly effective against adult worms. If
      mass treatment with these combination therapies achieves high coverage, they can
      have a large impact on lymphatic filariasis transmission.

PMID- 16640626
TI  - Circumsporozoite protein gene diversity among temperate and tropical Plasmodium
      vivax isolates from Iran.
AB  - To date, there is no information on the genetic diversity of the circumsporozoite
      protein (CSP), a leading vaccine candidate, in Plasmodium vivax populations
      circulating in Iran. The gene for this protein, Pvcsp, was amplified from 374 P.
      vivax isolates collected in the temperate northern, and in the tropical southern
      endemic areas. PCR-RFLP analysis of the repeated central region revealed that the
      parasites collected in the northern area were almost exclusively of the VK210
      type. Parasites collected in the south-eastern areas were of both VK210 and VK247
      types. We detected VK210 parasite in 70.5% of the samples, VK247 parasites in
      17.5% and mixed type infections in 12% of the isolates. Sequence analysis of 137
      isolates obtained from both areas identified a total of 25 distinct genotypes.
      The degree of genetic diversity was generally higher for the tropical (21
      genotypes) than the temperate (7 genotypes) P. vivax populations, a difference
      possibly reflecting the high cross-border exchanges between Afghanistan and
      Pakistan and southern Iran. Interestingly, all but two VK210 type isolates
      sequenced harboured a 36-bp post-repeat insert previously only observed in North
      Korea and China. This large-scale survey of parasite diversity in the Eastern
      Mediterranean Region provides a set of baseline data suitable for future
      molecular epidemiological studies of P. vivax.

PMID- 16640627
TI  - Seroepidemiology of leptospirosis in southern Vietnamese children.
AB  - OBJECTIVE: To estimate the seroprevalence of human leptospirosis in southern
      Vietnam. METHODS: All pupils (n=961) of two primary schools in two communes in
      southern Vietnam were screened for the presence of serum Leptospira
      immunoglobulin (Ig)G. Leptospira IgM was tested in 92 randomly selected samples.
      IgM and IgG were tested with a commercially available enzyme-linked immunosorbent
      assay (ELISA). RESULTS: Leptospira IgG was found in 123 (12.8%, 95% CI: 10.8
      15.1) children with a male:female ratio of 1.5:1. At the age of 7 years the
      prevalence was 11%. Log-linear binary regression of the IgG seroprevalence by age
      showed a mean seroconversion rate of 1.5% (95% CI: 1.23-1.75) per year. Five
      (5.4%, 95% CI: 2.3-12.1) samples were definitely positive for IgM. Presence of
      serum Leptospira IgG antibodies was significantly associated with swimming in
      rivers (RR: 1.745, 95% CI: 1.117-2.724) and wading through water (RR 1.793, 95%
      CI: 1.181-2.722). CONCLUSION: Our data emphasize the importance of leptospirosis
      among children in Vietnam, despite the absence of severe disease, and stress the
      need for adequate and cheap diagnostics.

PMID- 16640628
TI  - Risk of introduction of poliovirus into a Dutch Cape Verdian community during an
      outbreak of poliovirus in Cape Verde, 2000.
AB  - OBJECTIVE: To assess the risk of introduction of polio virus in a Cape Verdian
      community of Rotterdam, during the polio epidemic in Cape Verde in 2000. METHODS:
      All 225 insufficiently vaccinated 0-14-year-old Cape Verdian children (n=4188)
      and a random sample of 285 out of all 15-30-year-old Cape Verdians (n=5074) in
      Rotterdam were surveyed to assess travel behaviour and vaccination coverage.
      Faecal specimens were collected and sewage samples taken in neighbourhoods with a
      sizable Cape Verdian population for testing of polio virus. RESULTS: During the
      polio epidemic in Cape Verde, 10% of insufficiently vaccinated children aged 0-14
      years and 17% of adults aged 15-30 years living in Rotterdam reported travelling
      to Cape Verde. 94.6% of Cape Verdians in Rotterdam aged 0-14 years were
      sufficiently vaccinated against polio, but 9 of 91 insufficiently vaccinated
      children had travelled to Cape Verde during the epidemic. Of those aged 15-30
      years, 10% were not vaccinated against polio. In the faeces of 80 insufficiently
      vaccinated individuals aged 0-14 years and in 74 adults aged 15-30 years, no
      poliovirus was detected. Samples of sewage from six sites were negative for
      poliovirus. CONCLUSION: No evidence of poliovirus infection was found in the Cape
      Verde population in Rotterdam despite extensive travel to the Cape Verde during
      the outbreak.

PMID- 16640629
TI  - Intersections of 'sanitation, sexual coercion and girls' safety in schools'.
AB  - OBJECTIVE: To explore safety for girls in schools, particularly how girls
      perceive and negotiate dangers and risks associated with the use of toilets.
      METHODS: Participatory action research over a period of 3 days at three schools
      in South Africa. Informants were 81 girls 16 years and older, teachers and other
      relevant school personnel. Data were collected through focus group discussions,
      in-depth interviews, participant observation, mapping and photography. RESULTS:
      Toilets had inadequate or no sanitation. Both their use and their avoidance were
      risky for female students and discouraged hygienic practices. Experience of
      sexual violence from male students and teachers was a major theme, but unrelated
      to school toilets. Male teachers used various strategies and opportunities to
      gain sexual access to the girls and previous experience of victimization
      prevented the girls from reporting them. CONCLUSION: To ensure a healthy school
      environment that promotes gender equality, all threats to safety, including the
      physical and social environment, must be considered.

PMID- 16640630
TI  - The economic impact of visceral leishmaniasis on households in Bangladesh.
AB  - OBJECTIVES: To explore current patterns of diagnosis and treatment, quantify
      household economic impact and identify household strategies to cover the costs of
      visceral leishmaniasis (VL) care in rural Bangladesh. METHOD: Structured
      interviews with 113 VL patients from 87 households documenting all provider
      visits and expenditures for health care for VL, and the ways in which the
      expenditures were covered. RESULTS: Patients paid a median of 7 visits to six
      different providers before beginning VL treatment. All visited the subdistrict
      government hospital at least once. While health care, including antileishmanial
      drug therapy, is officially available free of charge at government facilities,
      79% of patients reported making informal payments for provider access,
      diagnostics and drug administration; only 14% of patients received their full
      drug course from this source. For the 58% of patients who purchased the full
      treatment course, drug cost constituted 34% of direct expenditure. Median direct
      expenditure for one VL patient was US$87 and median income lost was $40; median
      total expenditure was 1.2 times annual per capita income of our study population.
      Households employed multiple coping strategies to cover expenditures, most
      commonly sale or rental of assets (62%) and taking out loans (64%). CONCLUSIONS:
      Visceral leishmaniasis treatment causes a major economic burden in affected
      families. Control strategies for VL should facilitate timely, affordable
      diagnosis and treatment of patients to decrease the infection reservoir and to
      alleviate the economic burden of VL on households.

PMID- 16640631
TI  - Practical approach to lung health in Nepal: better prescribing and reduction of
      cost.
AB  - OBJECTIVES: To assess the impact of Practical Approach to Lung Health (PAL)
      guidelines on prescription behaviour and the total cost of prescription for
      patients with asthma, chronic obstructive pulmonary disease and pneumonia.
      METHODS: Pre- and post-intervention comparison in a cluster randomized trial of
      primary care facilities. Seven health posts and 33 subhealth posts in Nepal were
      stratified by type and randomized into intervention and control groups. Health
      workers from the intervention facilities received 5 days training on the adapted
      PAL guidelines and their use. To collect prescription details, we used carbon
      copy prescription pads in both groups. To measure the impact of PAL guidelines we
      used the World Health Organization's rational use of drug indicators and drug
      cost indicators, in a multivariate regression analysis. RESULTS: The PAL
      guidelines led to fewer prescriptions of multiple drugs and to more prescriptions
      of generic and essential drugs. The guidelines also lowered average prescription
      cost and wastage by disease except for chronic obstructive pulmonary disease
      although not to a statistically significant degree. Similarly, the prescription
      of antibiotics and adherence to guidelines improved, albeit not statistically
      significant. CONCLUSION: There is evidence that the implementation of PAL
      guidelines promotes rational use of drugs for some respiratory diseases. The
      expected health effects of PAL guidelines should be compared with their
      implementation costs before continuing training on lung health, and strategies
      put in place to sustain the effects.

PMID- 16640632
TI  - Consequences of and strategies to deal with residual post-treatment root canal
      infection.
AB  - Bacterial sampling of prepared root canals is used to determine the presence and
      character of the remaining microbiota. However, it is likely that current
      sampling techniques only identify organisms in the main branches of the root
      canal system whereas it is unlikely that they can sample areas beyond the apical
      end-point of preparation and filling, or in lateral canals, canal extensions,
      apical ramifications, isthmuses and within dentinal tubules. Thus, it may be
      impossible by current techniques to identify residual post-treatment root canal
      infection. In histologic observations of root apices, bacteria have been found in
      inaccessible inter-canal isthmuses and accessory canals often in the form of
      biofilms. There is no in vivo evidence to support the assumption that these
      bacteria can be entombed effectively in the canal system by the root filling and
      thus be rendered harmless. As a consequence of this residual root infection, post
      treatment apical periodontitis, which may be radiographically undetectable, may
      persist or develop as a defence mechanism to prevent the systemic spread of
      bacteria and/or their byproducts to other sites of the body. Histologic
      observation of root apices with surrounding bone removed from either patients or
      human cadavers has demonstrated that post-treatment apical periodontitis is
      associated with 50-90% of root filled human teeth. Thus, if the objective of root
      canal treatment is to eliminate apical periodontitis at a histological level,
      current treatment procedures are inadequate. It is essential that our knowledge
      of the local and systemic consequences of both residual post-treatment root
      infection and post-treatment apical periodontitis be improved. The continued
      development of treatments that can effectively eliminate root infection is
      therefore a priority in clinical endodontic research. Post-treatment disease
      following root canal treatment is most often associated with poor quality
      procedures that do not remove intra-canal infection; this scenario can be
      corrected via a nonsurgical approach. However, infection remaining in the
      inaccessible apical areas, extraradicular infection including apically extruded
      dentine debris with bacteria present in dentinal tubules, true radicular cysts,
      and foreign body reactions require a surgical intervention.

PMID- 16640633
TI  - Prostaglandin E production and viability of cells cultured in contact with
      freshly mixed endodontic materials.
AB  - AIM: To determine whether commonly used endodontic sealers could either induce or
      increase the release of prostaglandin E2 (PGE2) when in contact with cell types
      found in the periapical tissues. METHODOLOGY: Freshly mixed samples of Roth 801
      sealer, Sealapex and ProRoot mineral trioxide aggregate (MTA) were placed in
      contact with cultured macrophages and fibroblasts for 24 h. The supernatant from
      the cultures was assayed for PGE2 using enzyme-linked immunosorbent assay. Cell
      viability counts were made. As a positive control, similar cultures were also
      exposed to lipopolysaccharide and the supernatant analysed for PGE2. Data were
      compared by anova. RESULTS: The three materials examined in these experiments did
      not stimulate increased PGE2 release from either of the cell lines. In control
      cultures, lipopolysaccharide increased PGE2 release from macrophages but not from
      fibroblasts. Viability counts revealed that, whilst Roth 801 sealer caused some
      cell death in both fibroblasts and macrophages, Sealapex led to cell death only
      in the macrophage cultures. ProRoot MTA did not lead to statistically significant
      cell death in either culture. CONCLUSIONS: Under 24-h culture conditions, the
      three freshly mixed test materials did not increase directly either production or
      release of PGE2 from either macrophages or gingival fibroblasts. Roth 801
      decreased cell viability counts for both fibroblasts and macrophages. Sealapex
      decreases macrophage viability. ProRoot MTA did not affect viability in either
      cell line.

PMID- 16640634
TI  - Microleakage along Glassix glass fibre posts cemented with three different
      materials assessed using a fluid transport system.
AB  - AIM: To evaluate the microleakage along Glassix fibre posts cemented with three
      different materials. METHODOLOGY: The root canals of maxillary central incisor
      teeth were filled and restored with Glassix posts (Harald Nordin sa,
      Chailly/Montreux, Switzerland) cemented with either a zinc-phosphate Harvard
      cement (Richter & Hoffmann, Harvard Dental GmbH, Berlin, Germany), Fuji PLUS
      cement (GC Corporation, Tokyo, Japan) or Variolink II cement (Vivadent, Schaan,
      Lichtenstein) in three groups of 15 canals each. Twenty unrestored canals served
      as a control group, 10 filled with gutta-percha and sealer (negative control
      group), the remaining 10 with gutta-percha only (positive control group). Coronal
      microleakage was evaluated using a fluid transport system. The movement of an air
      bubble in a capillary glass tube connected to the apex of the experimental root
      section was measured over 5-min periods. Measurements were performed four times
      for each specimen and the mean values recorded. ANOVA and Duncan's test were
      performed. RESULTS: The positive control group had the highest values of
      microleakage. Amongst experimental groups, the highest values of microleakage
      occurred in the group with the posts cemented with Harvard cement, followed by
      Fuji PLUS and Variolink II cements. Groups with Fuji PLUS, Variolink II and the
      negative control group had significantly (P < 0.00001) less microleakage compared
      with the Harvard cement group and the positive control group. CONCLUSION: Canals
      with Glassix posts cemented with Variolink II and Fuji PLUS cement had the least
      leakage when assessed using a fluid transport system.

PMID- 16640635
TI  - Healing response of apicomarginal defects to two guided tissue regeneration
      techniques in periradicular surgery: a double-blind, randomized-clinical trial.
AB  - AIM: To compare healing responses to periosteal sliding grafts and polyglactin
      910 periodontal mesh used as guided tissue regeneration (GTR)
      materials/techniques when both periapical and periradicular bone loss are
      present. METHODOLOGY: Thirty patients with suppurative chronic apical
      periodontitis with apicomarginal communication were selected and allocated
      randomly into two groups according to the barrier technique to be used during
      periradicular surgery: periosteal graft group (n = 15) and bioabsorbable membrane
      group (n = 15). Clinical and radiological evaluations were completed prior to
      surgery, a week later and every 3 months after surgery up to 12 months to measure
      the periodontal pocket depth (PD), clinical attachment level (CAL), gingival
      margin position (GMP), size of periapical lesion, percentage reduction of the
      periapical rarefaction, and periapical healing. RESULTS: Both groups showed
      highly significant (P < 0.001) reductions in periodontal PD, CAL and size of
      periapical lesion at 12 months whilst GMP was unaltered. No significant
      difference between the experimental groups was evident for these parameters, or
      for the percentage reduction of size of the periapical lesion and clinical
      radiographic healing. CONCLUSION: Guided tissue regeneration applied to
      apicomarginal defects using sliding periosteal grafts and use of bioabsorbable
      membranes led to similar enhancements of the clinical outcome of periradicular
      surgery in terms of periapical healing, gain of periodontal support, PD reduction
      and minimal recession of the gingival margin.

PMID- 16640636
TI  - A laboratory analysis of gutta-percha-filled area obtained using Thermafil,
      System B and lateral condensation.
AB  - AIM: To determine the percentage of gutta-percha-filled area (PGFA) in the apical
      third of root canals when filled with either Thermafil, System B or lateral
      condensation. METHODOLOGY: Sixty extracted human maxillary central incisor teeth
      were root filled as following: G1: lateral condensation (n = 20), G2: System B (n
      = 20) and G3: Thermafil system (n = 20). A horizontal section was cut 2 and 4 mm
      from the apical foramen of each tooth. The samples were prepared for microscopic
      analysis and photomicrographs of each apical surface were taken at a
      magnification of 50x. Through digital image analysis, the cross-sectional area of
      the canal and the gutta-percha was measured. The PGFA was calculated. The PGFA
      data obtained in the three groups were analysed using a nonparametric Friedman
      and Wilcoxon signed-rank tests. RESULTS: Significant differences in PGFA were
      found between the Thermafil System (G3) and both System B (G2) and lateral
      condensation (G1) (P < 0.01). The greatest PGFA occurred in the Thermafil group.
      No significant statistical difference was found between System B and lateral
      condensation (P > 0.05). CONCLUSIONS: The coated carrier gutta-percha system
      Thermafil produced significantly higher PGFAs than lateral condensation and
      System B techniques.

PMID- 16640637
TI  - Reducing fear of pain associated with endodontic therapy.
AB  - AIM: To provide subjects with positive information about endodontic treatment
      (ET) to reduce fear of pain associated with ET. METHODOLOGY: A large sample (n =
      437) was randomly allocated to read one of five informative paragraphs and
      afterwards asked to complete two questionnaires (dental anxiety and fear of
      dental pain). The paragraphs consisted of dental information obtained from
      patient brochures. One (experimental) paragraph consisted of positive information
      about pain during ET. Analysis of variance followed by post hoc analysis was used
      to detect differences in mean score. RESULTS: Subjects who were given the
      positive information regarding ET indicated they were less fearful of pain
      associated with ET. CONCLUSIONS: The clinical implication of this experiment is
      that patients should be accurately informed about pain associated with ET. In
      this way, the patient may be more at ease before and during treatment, decrease
      avoidance behaviour and make decisions regarding treatment choice, based on
      common sense rather than fearful expectations.

PMID- 16640638
TI  - Mechanisms of cytotoxicity of eugenol in human osteoblastic cells in vitro.
AB  - AIM: To evaluate the mechanisms of cytotoxicity of eugenol in human osteoblastic
      cells in vitro. METHODOLOGY: Cytotoxicity and cell proliferation assays were
      performed to elucidate the toxic effects of eugenol on the human osteoblastic
      cell line U2OS. Furthermore, the effects of antioxidants catalase (scavenger of
      H2O2), superoxide dismutase (SOD, an extracellular superoxide free radical
      scavenger) and N-acetyl-L-cysteine (NAC, a cell-permeable glutathione precursor)
      were added to discover the possible mechanisms of eugenol-induced cytotoxicity.
      Paired Student's t-test was applied for the statistical analysis of the results.
      RESULTS: Eugenol demonstrated a cytotoxic effect to U2OS cells in a dose
      dependent manner (P < 0.05). The 50% inhibition concentration of eugenol was
      approximately 0.75 mmol L(-1). Eugenol also inhibited cell proliferation during a
      4-day culture period (P < 0.05). Addition of NAC extracellularly protected the
      cells from eugenol-induced cytotoxicity (P < 0.05). Neither, SOD nor catalase
      provided any protective effects on eugenol-induced cytotoxicity (P > 0.05).
      CONCLUSIONS: The levels of eugenol tested inhibited growth and proliferation of
      U2OS cells. Eugenol has significant potential for periapical toxicity. These
      inhibitory effects were associated with glutathione levels.

PMID- 16640639
TI  - Quantification of neuropeptides (calcitonin gene-related peptide, substance P,
      neurokinin A, neuropeptide Y and vasoactive intestinal polypeptide) expressed in
      healthy and inflamed human dental pulp.
AB  - AIM: To quantify the expression of calcitonin gene-related peptide (CGRP),
      substance P (SP), neurokinin A (NKA), neuropeptide Y (NPY) and vasoactive
      intestinal polypeptide (VIP) in healthy and inflamed human dental pulp tissue.
      METHODOLOGY: Six pulp samples were obtained from teeth having a clinical
      diagnosis of acute irreversible pulpitis. Another 12 pulp samples were obtained
      from premolars where extraction was indicated for orthodontic purposes. In six of
      these premolar teeth inflammation was induced by mechanical pulp exposure prior
      to sample collection. All samples were processed and 125I-labelled; neuropeptides
      were quantified by competition assays. ANOVA and Mann-Whitney's (post hoc) tests
      were used to establish statistically significant differences between the groups.
      RESULTS: Expression of five neuropeptides was found in all human pulp samples.
      Statistical analysis revealed a significantly higher (P < 0.05) expression of
      CGRP, SP, NKA and NPY in both inflammatory conditions compared with healthy pulp
      control values. VIP expression remained stable during the inflammatory
      conditions. CONCLUSION: Expression of CGRP, SP and NKA released from C-fibres and
      NPY released from sympathetic fibres is significantly higher in the inflamed
      human pulp compared with healthy pulp. Expression of VIP released from
      parasympathetic fibres is not increased during the inflammatory conditions of
      human dental pulp.

PMID- 16640640
TI  - Evaluation of the effect of EDTA, EDTAC and citric acid on the microhardness of
      root dentine.
AB  - AIM: To evaluate the effect of citric acid, ethylenediaminetetraacetic acid
      (EDTA) and ethylenediaminetetraacetic acid plus Cetavlon (EDTAC) solutions on the
      microhardness of human root canal dentine. METHODOLOGY: Sixteen maxillary human
      canines were sectioned transversely at the cemento-enamel junction and the crowns
      were discarded. Subsequently, each root was embedded in an epoxy resin cylinder
      and their middle third sectioned horizontally into 4 mm thick slices. The samples
      were randomly divided into three groups according to the chelating agent
      employed, as follows (n = 6): group 1: EDTA 17%, group 2: EDTAC 17% and group 3:
      citric acid 10%. Dentine microhardness was then measured with a load of 50 g for
      15 s. At the beginning of the experiment, reference microhardness values were
      obtained for samples without any etching (t = 0 min). The same samples were then
      exposed to 50 microL of the chelator solution for 1, 3 and 5 min. The Student's t
      test (P < 0.05) was used to compare results for different times for each chelator
      and different chelators for each time. RESULTS: Microhardness decreased with
      increasing time of application of chelating solutions. There were no significant
      (P > 0.05) differences between initial microhardness for the three groups as well
      as after 1 min of application of the substances. After 3 min, EDTA produced a
      significantly greater reduction in microhardness. However, there was no
      significant difference between EDTA and EDTAC after 5 min. Citric acid caused
      significantly less reduction in microhardness. CONCLUSIONS: Overall, citric acid
      was least effective in reducing dentine hardness whilst EDTA had the strongest
      effect.

PMID- 16640641
TI  - Ex vivo accuracy of three electronic apex locators: Root ZX, Elements Diagnostic
      Unit and Apex Locator and ProPex.
AB  - AIM: To compare ex vivo the accuracy of three electronic apex locators (EALs):
      Root ZX, Elements Diagnostic Unit and Apex Locator and ProPex. METHODOLOGY:
      Electronic working length determination was carried out in 40 extracted teeth
      using an ex vivo model. After access preparation, a first operator determined the
      reference length (AL) for each tooth under a 30x stereomicroscope using the
      apical constriction as the apical landmark. All teeth were then measured with
      each EAL and the results obtained were compared with the corresponding AL. The AL
      was subtracted from the electronically determined distance. The measurements
      exceeding the AL were recorded as positive (long) and the measurements short of
      the AL were recorded as negative. Data were analyzed using the Friedman Test and
      Tukey multiple range test for nonparametric correlation amongst groups.
      Statistical significance was considered at P < 0.05. RESULTS: Comparing the
      differences between measurements obtained with the three EALs and those obtained
      with the stereomicroscope, the percentage of measurements within +/-0.5 mm of the
      AL was 97.37% (84.22% within 0.5 mm short of AL) for the Root ZX, 94.28% (88.57%
      within 0.5 mm short of AL) for the Elements and 100% (35.9% within 0.5 mm short
      of AL) for the ProPex. The mean difference between the AL and the lengths
      measured by the Root ZX, the Elements and the ProPex were, respectively, -0.157
      +/- 0.228, -0.103 +/- 0.359 and 0.307 +/- 0.271 mm. CONCLUSIONS: The results of
      the present study confirm that the EALs determined the canal length within +/-0.5
      mm from the apical constriction in the majority of cases. The majority of the
      ProPex readings were long.

PMID- 16640642
TI  - Effect of mineral trioxide aggregate on proliferation of cultured human dental
      pulp cells.
AB  - AIM: To investigate the effect of mineral trioxide aggregate (MTA) on the
      proliferation of human dental pulp (HDP) cells ex-vivo. METHODOLOGY: Human dental
      pulp cells were cultured with MTA or calcium hydroxide-containing cement (Dycal)
      using culture plate inserts. Control cells were cultured with culture plate
      inserts only. Cell proliferation was measured for up to 14 days using a Cell
      Counting kit, and the concentration of calcium ions released from the tested
      materials was assessed using a Calcium E-test kit. To confirm that the effect of
      MTA was attributable to released calcium ions, cell proliferation was measured in
      the presence of exogenous calcium chloride as a source of calcium ions while in
      the absence of MTA. RESULTS: Mineral trioxide aggregate significantly stimulated
      cell proliferation after 12 days, whereas Dycal had no such effect. The number of
      calcium ions released from MTA was significantly higher than that released from
      Dycal. Following the addition of calcium chloride, cell proliferation increased
      in a dose-dependent manner after 12 days. Moreover, cell proliferation showed a
      similar pattern whether a given concentration of calcium ions was produced by
      calcium chloride or by release from MTA. CONCLUSIONS: In this ex-vivo study, the
      elution components such as calcium ions from MTA had higher proliferation ability
      of HDP cells than control and Dycal.

PMID- 16640643
TI  - Autophagic vacuolar myopathy in twin girls.
AB  - Hereditary autophagic vacuolar myopathy (AVM) may occur in several diseases
      including the rimmed vacuolar myopathies, acid maltase deficiency, Danon disease,
      infantile autophagic vacuolar myopathy and X-linked myopathy with excessive
      autophagy (XMEA). In the latter three conditions the vacuoles are lined by
      membranes with sarcolemmal features. We present two unusual cases of autophagic
      vacuolar myopathy in twin girls born at term with no family history of
      neurological disease. After initial normal developmental milestones they
      developed progressive leg weakness and wasting with contractures from the age of
      12 years. Investigations showed raised CK, normal female karyotype, normal acid
      maltase activity, normal nerve conduction and myopathic EMG features. Frozen
      sections of skeletal muscle were stained using routine tinctorial and
      histochemical methods. Immunohistochemical staining for spectrin, merosin,
      dystrophin, complement membrane attack complex and sarcoglycans was performed and
      ultrastructural examination undertaken. Direct sequence analysis of the lamp-2
      gene using genomic DNA extracted from lymphocytes was performed. Histological
      analysis of the muscle biopsies demonstrated myofibres with vacuoles lacking
      glycogen and lipid many of which were delineated using immunohistochemistry for
      merosin, dystrophin and sarcoglycans. Ultrastructural examination showed
      duplication of the myofibre basal lamina with associated autophagic material.
      Vacuoles within myofibres were either membrane bound containing autophagic
      material or lined by plasma membrane and basal lamina. Intermyofibrillar glycogen
      was increased. Sequence analysis of the coding region and intron/exon boundaries
      of the lamp-2 gene was normal. This is the first report of female cases of AVM
      with sarcolemmal features. We suggest that these patients may represent
      manifesting carriers of XMEA, or alternatively, a new form of disease with a
      similar phenotype having autosomal recessive inheritance.

PMID- 16640644
TI  - Methodological aspects of 3D and automated 2D analyses of white matter neuronal
      density in temporal lobe epilepsy.
AB  - White matter neuronal density has been correlated with clinical outcome after
      temporal lobectomy for refractory epilepsy. Both morphometric 2D (two
      dimensional) and stereological 3D (three-dimensional) analyses of neuronal
      density have been performed. 3D analyses are thought to be more accurate than 2D
      counts, but more time-consuming. We compared 3D and automated 2D measurements in
      the same specimens. Adjacent 20-microm (for 3D analyses) and 5-microm (for 2D
      analyses) sections from 10 temporal lobectomies were stained for NeuN
      immunohistochemistry. Analysis of 100% of a region of interest (ROI) in deep
      white matter was performed using an image analysis system (Histometrix, Kinetic
      Imaging, UK). 3D analyses were undertaken using x 63 magnification (6 h/case).
      Automated 2D analyses were undertaken using automatic neuronal identification at
      x 10 magnification with three to four repeats (1.5 h/case). The range of neuronal
      densities for 3D measurements was 2120-4910 neurones/mm(3), and for automated 2D
      measurements 17.4-47.1 neurones/mm2. There was a linear correlation between the
      two methods with an r2 of 0.58. [corrected] Count-recount variability was 1.4
      9.9% for the 3D and 5.1-36.6% for the automated 2D measurements. We found a wide
      range of white matter neuronal densities using either analysis. The low agreement
      between methods, and the high count-recount variability for the automated 2D
      analyses, indicate that despite being more time-consuming, rigorous 3D
      stereological analyses have to be performed to obtain reliable results. These
      findings have implications for studies requiring neuronal counts in normal and
      disease states.

PMID- 16640645
TI  - Knockdown of annexin 2 decreases migration of human glioma cells in vitro.
AB  - Diffuse invasion of brain tissue is a major reason for the poor prognosis of
      patients with glioblastoma. Annexin 2, a member of the large annexin family of
      Ca2+ and membrane-binding proteins, is expressed at high protein levels in human
      gliomas and has been proposed as a marker of glioma malignancy, while its
      functional role in these tumours is unknown so far. The ability of annexin 2 to
      interact with the actin cytoskeleton, as well as its potential to bind invasion
      associated proteases, suggests that it could participate in invasion-associated
      processes in human gliomas. Therefore, we analysed here functional consequences
      of RNA interference-mediated silencing of annexin 2 in U87MG and U373MG human
      glioma cell lines. While no impact of annexin 2 downregulation on proliferation
      and adhesion was observed, our analyses revealed that migration of U87MG and
      U373MG cells was significantly inhibited following annexin 2 depletion. This
      effect was not related to a compensatory increase of the related annexins 1 or 6.
      Our findings identify annexin 2 as a potential candidate involved in glioma
      invasion and support the potential of RNA interference as powerful tool in the
      decryption of glioma invasion mechanisms.

PMID- 16640646
TI  - Immunohistochemical profile and chromosomal imbalances in papillary tumours of
      the pineal region.
AB  - The histopathology of papillary tumours of the pineal region (PTPR) closely
      resembles that of ependymomas and choroid plexus tumours. Therefore,
      immunohistochemical staining profiles were investigated in a series of 15 PTPR.
      In addition to cytokeratin, synaptophysin and glial fibrillary acidic protein
      expression, PTPR were examined for the presence of dot- or ring-like epithelial
      membrane antigen (EMA) immunoreactivity typically encountered in ependymoma,
      staining for inwardly rectifying potassium channel Kir7.1 and stanniocalcin-1
      (specifically expressed in choroid plexus tumours) as well as microtubule
      associated protein-2 (MAP-2). Furthermore, comparative genomic hybridization was
      performed in five PTPR. Cytokeratin was expressed in all PTPR examined, whereas
      glial fibrillary acidic protein and synaptophysin staining were absent. Dot- or
      ring-like EMA immunoreactivity was only observed in 1 out of 15 PTPR. Membranous
      Kir7.1 and cytoplasmic stanniocalcin-1 staining were present in the minority of
      PTPR (3/15 and 4/15, respectively). In contrast, MAP-2 immunoreactivity was
      encountered in 13 out of 15 PTPR, but was significantly less frequently observed
      in a series of choroid plexus tumours (7/37). PTPR mainly presented with
      chromosomal losses affecting chromosomes 10 (4/5 cases) and 22q (3/5 cases) as
      well as gains on chromosomes 4 (4/5 cases), 8 (3/5 cases), 9 (3/5 cases) and 12
      (3/5 cases). To conclude, the majority of PTPR can be distinguished from
      ependymomas and choroid plexus tumours by absent staining for epithelial membrane
      antigen, Kir7.1 and staniocalcin-1 as well as the presence of distinct MAP-2
      immunoreactivity. Antibodies directed against these antigens are thus expected to
      be valuable markers in the diagnosis of papillary tumours located in the vicinity
      of the third ventricle.

PMID- 16640647
TI  - Alpha-synuclein pathology of the spinal and peripheral autonomic nervous system
      in neurologically unimpaired elderly subjects.
AB  - Studies on cases with incidental Lewy body disease (ILBD) suggest that alpha
      synuclein (alphaSN) pathology of Parkinson's disease (PD) starts in lower
      brainstem nuclei and in the olfactory bulb. However, medullary structures as the
      induction site of alphaSN pathology have been questioned as large parts of the
      nervous system, including the spinal cord and the peripheral autonomic nervous
      system (PANS), have not been examined in ILBD. Thus, the time course of PD
      lesions in the spinal cord or PANS in relation to medullary lesions remains
      unknown. We collected 98 post mortem cases with no reference to PD-associated
      symptoms on clinical records. alphaSN pathology was found in the central nervous
      system, including the spinal cord, and in the PANS in 17 (17.3%) cases. alphaSN
      pathology was encountered in autonomic nuclei of the thoracic spinal cord,
      brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in
      15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in
      14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral
      horns, a high number of alphaSN lesions was also found in non-autonomic spinal
      cord nuclei. Considering supraspinal structures our cases corresponded roughly to
      the recently described sequential order of alphaSN involvement in PD. Our study
      indicates, however, that the autonomic nuclei of the spinal cord and the PANS
      belong to the most constantly and earliest affected regions next to medullary
      structures and the olfactory nerves. A larger cohort of ILBD cases will be needed
      to pinpoint the precise induction site of alphaSN pathology among these
      structures.

PMID- 16640648
TI  - A study of the serotonin transporter in the prefrontal cortex in late-life
      depression and Alzheimer's disease with and without depression.
AB  - Previous studies investigating the serotonin transporter (SERT) in depression
      have been inconsistent and included a large proportion of subjects who had
      committed suicide. In Alzheimer's disease studies have generally reported a
      reduction in SERT density but have not compared Alzheimer's disease subjects with
      and without comorbid major depression. We conducted a post mortem study of SERT
      density in the prefrontal cortex in normal elderly, a group of elderly depressed
      subjects and in Alzheimer's disease subjects with and without major depression. A
      post mortem study comparing SERT density in the prefrontal cortex in elderly
      controls (n = 10), subjects with major depression (n = 8) and subjects with
      Alzheimer's disease with (n = 9) and without (n = 5) comorbid major depression.
      We used autoradiography to measure the density of [3H]CN-IMI binding (non
      specific binding determined with citalopram) to the SERT in the prefrontal
      cortex. We found a marked reduction in specific SERT binding in the prefrontal
      cortex in Alzheimer's disease subjects compared with both control (P = 0.002) and
      depressed subjects (P = 0.004) but no difference in SERT binding between
      depressed and control subjects or between Alzheimer's disease subjects with and
      without depression. Our study confirms previous reports of a reduction in SERT
      binding in Alzheimer's disease but indicates this reduction is not greater in
      Alzheimer's disease subjects who also have had major depression. In a group of
      subjects more typical of late-life depression we did not identify any alterations
      in SERT density.

PMID- 16640649
TI  - Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are
      upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in
      children.
AB  - We investigated the protein expression of gelatinases [matrix metalloproteinase
      (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF)
      from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In
      both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was
      detectable in 53% and 82% respectively. Three patients with clinical signs of
      meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8
      appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and
      fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar
      punctures showed that these MMPs are independently regulated, and correlate only
      partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor
      of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear
      cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could
      be found only in the former two cell types. Using models of exogenous (n-formyl
      Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin
      2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation
      between these immune cells and suggest release from preformed stocks. In
      addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion,
      invading immune cells contribute only partially to MMPs in CSF during meningitis,
      and parenchymal cells are an equally relevant source. In this context, in
      patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs
      seem to be a highly sensitive marker for intrathecal inflammation. The present
      data support the concept that broad-spectrum enzyme inhibition targeting
      gelatinases and collagenases is a potential strategy for adjunctive therapy in
      infectious meningitis.

PMID- 16640650
TI  - Growth-associated protein 43 in lesions and cerebrospinal fluid in multiple
      sclerosis.
AB  - Axonal damage in multiple sclerosis (MS) is correlated to disease progression.
      Early axonal damage may be compensated for by regenerative processes. Growth
      associated protein 43 (GAP-43) is a marker for axonal growth and synaptogenesis
      in various neurodegenerative diseases. We investigated the expression of GAP-43
      in 48 MS grey and white matter lesions of different stages. Decreased GAP-43
      expression was found in 74% of the white matter lesions, independent of the
      lesion stage. In 19 out of 35 white matter lesions, areas of increased GAP-43
      expression were present immediately adjacent to the lesions. Increased or
      unaltered expression was observed in remyelinated lesions. GAP-43 was expressed
      in neurofilament-positive structures. GAP-43 expression appeared unchanged in
      grey matter lesions. Macrophages were present in the areas of changed GAP-43
      expression. cerebrospinal fluid GAP-43 levels were negatively correlated with
      magnetic resonance imaging measures of whole-brain atrophy (r = -0.30). In
      conclusion, these results indicate that decreased GAP-43 immunopositivity
      reflects axonal damage in MS lesions, which may again be reflected in decreased
      cerebrospinal fluid levels. The increased levels of GAP-43 in remyelinated or
      nondemyelinated white matter close to MS lesions may reflect regenerative
      attempts by damaged axons.

PMID- 16640651
TI  - Relationships in Alzheimer's disease between the extent of Abeta deposition in
      cerebral blood vessel walls, as cerebral amyloid angiopathy, and the amount of
      cerebrovascular smooth muscle cells and collagen.
AB  - The relationship between degree of cerebral amyloid angiopathy (CAA) and the
      amount of smooth muscle cells (SMCs) and deposition of collagen IV fibres (COL
      IV) was investigated in the frontal and occipital cortex of 70 patients with
      autopsy confirmed Alzheimer's disease (AD). The extent of CAA was significantly
      greater in occipital than in frontal cortex, although SMC loss was greater in
      frontal than in occipital cortex. COL IV staining was significantly higher in
      occipital than in frontal cortex. The degree of SMC loss correlated with CAA, as
      Abeta40 but not as Abeta42 or total Abeta, in frontal cortex, but not in
      occipital cortex. Leptomeningeal arteries within occipital cortex showed
      significantly greater external diameter, greater wall thickness and greater
      luminal area than those in frontal cortex. The degree of CAA correlated with
      thickness of blood vessel wall and external diameter in frontal cortex, whereas
      extent of SMC loss correlated with thickness of blood vessel wall in occipital
      cortex. There were significant negative correlations between duration of disease
      and thickness of vessel wall, external diameter and luminal area. In patients
      with disease durations exceeding 10 years, external vessel diameter and thickness
      of the vessel wall were both halved compared with patients with durations less
      than 5 years; luminal area was reduced by about 75%. Blood vessels in AD undergo
      degenerative changes involving deposition of Abeta and COL IV with loss of SMC.
      SMC loss may relate to increasing Abeta deposition in early stages of disease,
      but this relationship may be lost with disease progression.

PMID- 16640652
TI  - Commentary on: Return of the cycad hypothesis--does the amyotrophic lateral
      sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications
      for global health?

PMID- 16640653
TI  - Neuropathological analysis of an asymptomatic adult case with Dandy-Walker
      variant.
AB  - The Dandy-Walker (DW) complex is a rare posterior fossa malformation, usually
      observed during the prenatal period or the early infancy. Clinically, it is
      characterized by mental retardation, seizures, cerebellar ataxia as well as
      symptoms of hydrocephalus. Structural imaging reveal a hypoplasia or agenesis of
      the cerebellar vermis, enlargement of the fourth ventricle with a posterior fossa
      cyst. Additional neurodevelopmental changes such as agenesis of the corpus
      callosum, lissencephaly and cortical dysplasia are also present. We report the
      first neuropathological analysis of an adult asymptomatic DW case. Brain
      computerized tomography showed a massive posterior fossa cyst and hypoplasia of
      the cerebellum. An Ehlers-Danlos syndrome type IV characterized by repetitive
      intestinal perforations and a saccular aneurysm on the left posterior
      communicating artery was also present. Macroscopic brain examination revealed
      hypoplasia of both cerebellar hemispheres and posterior part of the vermis, as
      well as dilatation of the fourth ventricle without hydrocephalus. The posterior
      fossa cyst wall was formed by an external arachnoid layer, middle layer with
      loose connective tissue and an internal layer of ependymal cells. There were two
      foci of cerebellar cortical dysplasia but no ectopic neurons, neuronal loss or
      gliosis in both cerebellum and cerebral cortex. No vascular or significant
      neurodegenerative lesions were observed. In comparison with previous reports in
      DW infants, this adult case displayed milder brain abnormalities compatible with
      a diagnosis of DW variant. The preservation of the cortical cytoarchitecture as
      well as the paucity of additional neurodevelopmental changes may explain the
      absence of clinical expression.

PMID- 16640654
TI  - Comparative study of commercially available anti-alpha-synuclein antibodies.
AB  - Immunohistochemistry for alpha-synuclein has become the histological technique of
      choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and
      Multiple System Atrophy (http://www.ICDNS.org). Nevertheless, no standardised
      protocol has been proposed. We have reviewed 242 of the 270 studies published
      until June 2005 that mentioned immunohistochemistry for anti-alpha synuclein on
      human tissue and we found that only 75 (31%) used commercial antibodies. We also
      noted that protocols, particularly dilution and antigen unmasking, varied between
      studies, even when the same antibody was employed. In order to establish a
      standardised protocol for alpha-synuclein immunohistochemistry, which can be
      applied in diagnostic neuropathology we tested seven commercial monoclonal
      antibodies in brains of subjects with Parkinson's disease, dementia with Lewy
      bodies, multiple system atrophy, multiple sclerosis with incidental Lewy bodies
      and aged-matched normal brain and determined for each antibody the best suited
      protocol for antigen unmasking. We evaluated the intensity of immunolabelling in
      Lewy bodies, neuropil threads, dendrites, pre-synaptic terminals, granular
      cytoplasmic positivity, peri-axonal positivity, glial inclusions and non-specific
      immunolabelling. Although our results showed that all the antibodies detected
      alpha-synuclein inclusions, differences were noted between antibodies,
      particularly with regard to the detection of glial inclusions. From our study,
      the best antibodies of the seven tested appeared to be those directed against
      amino acids 116-131 and 15-123 and we suggest them to be used in routine
      diagnostic practice for alpha-synucleinopathies.

PMID- 16640655
TI  - Interleukin-6 trans-signalling in chronic inflammation and cancer.
AB  - Interleukin-6 (IL-6) is a cytokine, which plays an important role in many chronic
      inflammatory diseases. IL-6 belongs to a family of 10 cytokines, which all act
      via receptor complexes containing the cytokine receptor subunit gp130. On cells,
      IL-6 first binds to a specific membrane-bound IL-6R and the complex of IL-6 and
      IL-6R interacts with gp130 leading to signal initiation. Whereas gp130 is widely
      expressed throughout the body, the IL-6R is only found on some cells including
      hepatocytes and some leucocytes. A soluble form of the IL-6R is an agonist
      capable of transmitting signals through interaction with the gp130 protein. In
      vivo, the IL-6/soluble IL-6R complex stimulates several types of target cells,
      which are unresponsive to IL-6 alone, as they do not express the membrane-bound
      IL-6R. We have named this process trans-signalling. We provided evidence that a
      soluble form of the IL-6 family signalling receptor subunit gp130 is the natural
      inhibitor of IL-6 trans-signalling responses. We showed that in chronic
      inflammatory diseases such as inflammatory bowel disease, peritonitis, rheumatoid
      arthritis, asthma as well as in colon cancer, IL-6 trans-signalling is critically
      involved in the maintenance of the disease state. Moreover, in all these animal
      models, the progression of the disease can be interrupted by specifically
      interfering with IL-6 trans-signalling using recombinant-soluble gp130Fc protein.
      The pathophysiologic mechanisms by which the IL-6/soluble IL-6R complex
      perpetuates the inflammatory state are discussed.

PMID- 16640656
TI  - Peroxisome proliferator-activated receptor alpha, delta, gamma1 and gamma2
      expressions are present in human monocyte-derived dendritic cells and modulate
      dendritic cell maturation by addition of subtype-specific ligands.
AB  - It has recently been shown by Chang et al. (J Immunol 2000;165:3584-91) that the
      maturation of dendritic cells (DC) in the presence of long-chain fatty acids
      redirects DC into Th0/Th2-inducing cells suggesting the involvement of a receptor
      for long-chain fatty acids like members of the peroxisome proliferator-activated
      receptors (PPAR) superfamily. Here, we show that immature and mature monocyte
      derived DC (Mo-DC) express PPARalpha, PPARdelta, PPARgamma1 and PPARgamma2 mRNA
      with the highest level of PPARgamma1 mRNA. We were only able to observe the
      expression of PPARgamma1 protein by Western blotting probably because the protein
      level of the other subtypes is below the detection limit. Synthetic ligands
      specific for PPARalpha, PPARdelta or PPARgamma added at day 0-6 have similar
      effect on the maturation of Mo-DC driving the maturation of Mo-DC with atypical
      phenotype, reduced expression of IL-10, IL-12 p35 and IL-12 p40 mRNA and with
      reduced stimulatory effects in mixed leucocyte reaction (MLR). Our data suggest
      that naturally occurring PPAR ligands like fatty acids and fatty acid derivates
      have anti-inflammatory effects by redirecting DC into a less stimulatory mode.

PMID- 16640657
TI  - The unveiling of hidden T-cell determinants of a native antigen by defined
      mediators of inflammation: implications for the pathogenesis of autoimmunity.
AB  - A major hypothesis for the induction of autoimmunity invokes the enhanced display
      of previously hidden (cryptic) epitopes under inflammatory conditions leading to
      the activation of self-reactive T cells. However, there is meager data that
      directly validate the influence of specific immune mediators on the upregulation
      of the presentation of cryptic determinants in vivo. We tested the effect on well
      defined cryptic epitopes of hen eggwhite lysozyme (HEL) of the availability
      locally of a cytokine (IL-2, IL-4, IL-6, IL-10, TNF-alpha or granulocyte
      macrophage colony-stimulating factor) at the antigen delivery site, or of the
      pretreatment of the immunogen with a cathepsin (Cat B, D, L or S) prior to use in
      vivo. Each of the three mouse strains (H-2(b/d/k)) tested revealed a unique
      profile of T-cell reactivity to different cryptic epitopes of HEL in response to
      a particular cytokine or cathepsin. These results provide proof of principle for
      the reversal of crypticity of self-epitopes by immune mediators in the local
      milieu. Moreover, co-immunization with an antigen and a cytokine offers a simple
      and reliable tool for studying the role of cryptic epitopes in autoimmunity. Our
      results also strengthen the rationale for the use of inhibitors of
      cytokine/cathepsin activity in the treatment of autoimmune diseases.

PMID- 16640658
TI  - IgG immune complex-binding in macrophages from arthritis-susceptible and
      arthritis-resistant mice following collagen type II immunization.
AB  - Occupancy of Fc gamma receptors (FcgammaR) by immune complexes (IC) induces
      secretion of various inflammatory mediators and cytokines. Therefore, knowledge
      of the FcR function is fundamental for understanding inflammatory processes.
      Here, we report an alteration in the FcR function in collagen-induced arthritis
      (CIA). The FcgammaR-binding activity of peritoneal macrophages from arthritis
      susceptible DBA/1 mice following collagen type II (CII)/CFA immunization was
      assessed by Fc rosetting of SRBC opsonized with different IgG subclasses. A
      progressive reduction of IgG1 IC-binding was observed after immunization, and by
      the time of arthritis onset, the IgG1 IC-binding was abolished. Binding of IgG2a
      or IgG2b IC, however, was not affected. The blocked IgG1 IC-binding was reversed
      by a prior mild acid wash of the CIA macrophages, indicating receptor occupancy
      as the cause of the blocked binding. The impaired IgG1 IC-binding was associated
      with arthritis development, as macrophages from CII/CFA-immunized, arthritis
      resistant SWR mice or DBA/1 mice, immunized with CFA alone, did not show this
      effect. Normal DBA/1 macrophages, blocked with a monoclonal antibody to
      FcgammaRIIB/FcgammaRIII, and macrophages from FcgammaRIII-deficient mice did not
      bind IgG1 IC, indicating FcgammaRIII as responsible for IgG1 IC-binding. Our data
      suggest that an increased degree of saturation of FcgammaRIII precedes the
      development of CIA, which is reflected by a reduced IgG1 IC-binding in
      macrophages of CII/CFA-immunized DBA/1 mice.

PMID- 16640659
TI  - Minimal residual disease in ovarian cancer as a target for complement-mediated
      mAb immunotherapy.
AB  - Ovarian cancer is potentially well suited for local monoclonal antibody (mAb)
      immunotherapy, because it remains within the peritoneal cavity for a long period
      of time before giving rise to distant metastases. At the stage of minimal
      residual disease, the cells appear to be in a state of dormancy (G(0)) or at
      least have lower rates of tumour cell proliferation. They should be a promising
      target for immunotherapy. Here we first examined the cell-cycle expression of
      CD59 and decay-accelerating factor (DAF; CD55) on four different ovarian
      carcinoma cell lines, using simultaneous flow cytometric analysis of DNA content
      or the cell-cycle-specific nuclear proliferation protein Ki67 and CD59 or DAF
      surface expression. We found that CD59 and DAF are stably expressed throughout
      the cell cycle. The polyvalent approach to target-independent antigens to improve
      the efficiency of mAb complement (C)-mediated damages was promising, and tumour
      cells become sensitive to C damage, when incubated with cross-linked mAb against
      different tumour-associated antigens. Although, such immune complex-mediated C
      activation was rather ineffective in killing the cells, it could be potentiated
      by the addition of blocking mAb against CD59 and DAF. Our results suggest that
      the activities of intrinsic C regulators must be neutralized to make minimal
      residual disease a promising target for antibody therapy.

PMID- 16640660
TI  - Nematode infection in Alymphoplasia (aly) mice: worm species-dependent
      differential effect of defects of the gut-associated lymphatic tissue system.
AB  - Mice homologous for the alymphoplasia mutation (aly) show the systemic absence of
      secondary lymphoid tissues, with disorganized splenic architecture, including the
      absence of the germinal centre and follicular dendritic cells. In this study, we
      examined the influence of defects of gut-associated lymphoid tissue (GALT), such
      as Peyer's patches and the mesenteric lymph nodes, on the host response to
      helminth infection in aly/aly mice. The present study showed that most of the
      worms were expelled by day 7 after Nippostrongylus brasiliensis infection in both
      control aly/+ and aly/aly mice. In aly/aly mice, the number of peripheral blood
      eosinophils, intestinal goblet cells and mucosal mast cells were increased by N.
      brasiliensis infection in aly/aly mice to the same level as in the controls.
      Conversely, aly/aly mice developed more severe Heligmosomoides polygyrus
      infections than control aly/+ mice, as demonstrated by increased faecal egg
      counts, with reduced immune responses such as the numbers of intestinal goblet
      cells and mucosal mast cells. These results suggested that the dependency of GALT
      in activation of Th2 responses against gastrointestinal nematodes was different
      depending on the species of nematode.

PMID- 16640661
TI  - Expression of idiotypic antibodies-1 and -2 and breastfeeding in relation to
      antibody levels against Haemophilus influenzae type B in children.
AB  - The aim of the study was to determine the concentrations of serum antibodies
      against Haemophilus influenzae type b in preschool children in relation to the
      distribution of idiotypic antibodies 1 and 2 (Id-1 and Id-2) and the exposure to
      breastfeeding in infancy. Sera were obtained from 74 control children recruited
      in an earlier case-control study before the introduction of general Hib
      vaccination. Duration of breastfeeding was monitored, and prevalence of
      noninvasive infections was registered. Concentrations of IgG1 and IgG2 anti-Hib,
      as well as of total Id-1 and Id-2, were determined in ELISA. The expression of Id
      1 antibodies increased with age in contrast to the Id-2 antibodies that were
      found only in children up to 24 months of age. Expression of Id-1 antibodies was
      positively correlated with higher anti-Hib levels of both the IgG1 and IgG2
      isotype. Children expressing Id-2 antibodies showed higher IgG2 anti-Hib
      concentrations than those who did not have Id-2 (P = 0.001). The concentrations
      of neither Id-1 nor Id-2 antibodies were related to the duration of
      breastfeeding. Duration of breastfeeding was related to increased anti-Hib IgG2
      in healthy children above 18 months of age. These study shows that the expression
      of idiotype-1 and idiotype-2 antibodies was associated with higher IgG2 anti-Hib
      concentration and that breastfeeding could enhance the anti-Hib IgG2 production
      in children.

PMID- 16640662
TI  - Anti-p97/VCP antibodies: an autoantibody marker for a subset of primary biliary
      cirrhosis patients with milder disease?
AB  - We previously reported that 12.5% of primary biliary cirrhosis (PBC) sera reacted
      with a 95 kDa cytosol protein (p95c) that was subsequently identified as a
      p97/valosin-containing protein (VCP). The clinical features and course of the six
      anti-p97/VCP-positive PBC patients with Scheuer's stage 1 and 2 liver biopsies
      were monitored for an average of 15 years. This group was compared with 50 PBC
      patients that did not have detectable anti-VCP. Autoantibodies to a full-length
      recombinant p97/VCP were assayed by immunoprecipitation. All six PBC patients
      with anti-VCP had antibodies to the mitochondrial pyruvate dehydrogenase complex
      E2 antigen as measured by an addressable laser bead immunoassay. The first was a
      male with no evidence of liver failure that died of cerebral infarction at the
      age of 85. The second was a 73-year-old female with Hashimoto's thyroiditis who
      has remained clinically stable without ursodeoxycolic acid (UDCA) treatment.
      Although the third had no HCV antibodies, he developed hepatocellular carcinoma
      at the age of 76 and died of renal failure at 78. The fourth was a 50-year-old
      female who remained clinically stable during follow-up and the fifth with
      Hashimoto's thyroiditis and stable liver function following UCDA treatment. The
      sixth was a male patient presenting a mild clinical course. The clinical course
      of these patients was in contrast to the 50 comparison group PBC patients who did
      not have anti-p97/VCP. As the six PBC patients with anti-p97/VCP antibodies had
      slowly progressive liver disease and no mortality related to autoimmune liver
      disease, our observations suggest that this autoantibody might be an indicator of
      a favourable prognosis.

PMID- 16640663
TI  - Costimulatory molecules and cytokine production by T lymphocytes in common
      variable immunodeficiency disease.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized
      by hypogammaglobulinaemia and recurrent infections. Although early works pointed
      to a primary B-lymphocyte defect as a cause of the disease, a failure in T
      lymphocyte cooperation has also been suggested. T cells exert their costimulatory
      function through either membrane costimulatory molecules or secreted cytokines,
      both having an influence in the development of the humoral response. The aim of
      our study was to evaluate whether an abnormal expression and induction of
      costimulatory molecules or alterations in the production of cytokines by T cells
      cause deficient T/B cooperation in CVID patients. We studied the expression and
      upregulation of costimulatory molecules (CD28, CD40L/CD154 and CTLA-4/CD152) and
      production of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) in
      purified T lymphocytes from CVID patients stimulated with optimal doses of anti
      CD3 or suboptimal doses of anti-CD3 and anti-CD28. Stimulated T cells from CVID
      patients expressed normal levels of CD28, CD40L/CD154 and CTLA-4/CD152 when
      compared with controls. Except for higher production of IL-4 after stimulation
      with anti-CD3, T cells of CVID patients produced similar amounts of cytokines
      compared with controls. An imbalance between costimulatory molecules expression
      (CD28, CD40L/CD154 and CTLA-4/CD152) and cytokine production by T cells does not
      explain a deficient cooperation between T and B cells in this group of CVID
      patients.

PMID- 16640676
TI  - Novel face-lift suspension suture and inserting instrument: use of large anchors
      knotted into a suture with attached needle and inserting device allowing for
      single entry point placement of suspension suture. Preliminary report of 20 cases
      with 6-to 12-month follow-up.
AB  - BACKGROUND: Various suspension suture techniques exist to elevate the mid-face,
      jowls, and neck. OBJECTIVE: To assess safety and efficacy of a new suspension
      suture and inserting instrument with both standard and minimal incision (no-skin
      excision) face-lifts. METHODS: A new type of multianchor suspension suture
      assembled from commercially available 2-0 absorbable monofilament material, with
      5 to 9 equally spaced knots through which are secured 7 to 9 mm bits of 0
      thickness similar suture material, and an attached straightened needle, was used
      to elevate and suspend facial tissues to temporal or mastoid fascia. The
      suspension sutures are placed in the deep subcutaneous tissues, just above the
      superficial musculo aponeurotic system (SMAS), by use of a novel, blunt
      instrument, which does not require a second, distal exit point. The suspension
      suture distal end floats free. The proximal needle end is sutured to fascia. The
      suture was used on 20 patients. Fourteen of them underwent pure, "no-skin
      excision," suspension lifts. Six had suspension suture elevation of the mid-face
      in conjunction with relatively conservative open lifts. Nine- to 12-month results
      were evaluated. RESULTS: With open face-lifts, 9- to 12-month results are
      excellent with significant persistence of the correction initially achieved.
      Resulting scars remained fine line. There were no complications. With pure
      suspension lifts, initial results were impressive. By 6 months, correction
      started to fade. By 12 months 100% of initial correction for jowls, and 80 to
      100% for mid-face, appeared lost. Recovery time was 2 to 4 days. There were no
      significant complications. CONCLUSION: Large multianchor, absorbable monofilament
      sutures can safely and effectively enhance results of conservative lifts, with
      remarkable elevation of the mid-face not achievable with simple SMAS flaps. These
      suspension sutures can easily and safely achieve impressive, though relatively
      short-term results, with a minimal incision, "no-skin-excision" technique.

PMID- 16640677
TI  - Patient satisfaction and reported long-term therapeutic efficacy associated with
      1,320 nm Nd:YAG laser treatment of acne scarring and photoaging.
AB  - BACKGROUND AND OBJECTIVE: Nonablative laser treatments have become increasingly
      used for the treatment of acne scarring and photoaging. While nonablative laser
      treatments are more convenient and relatively safer than ablative laser
      resurfacing, efficacy and patient satisfaction with the level of improvement of
      textural abnormalities in acne scarring and rhytids associated with photoaging
      needs further study. DESIGN/MATERIALS AND METHODS: Structured interviews were
      performed with 34 patients from a referral-based academic practice who each
      previously received a series of 6 monthly treatments with a 1,320 nm
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for treatment of acne scarring
      or photoaging. Topical anesthesia was applied 1 hour before each treatment.
      Patients were interviewed at least 3 months after cessation of treatment (range 3
      12 months). RESULTS: Patients tolerated the treatments well. Combined results for
      acne scarring and photoaging patients were as follows: (a) patient satisfaction
      with treatment was rated at 62%, and (b) textural improvement was reported at 31%
      at the end of the six treatments, and 30% at the date of interview. When results
      were stratified by diagnosis, patient satisfaction was slightly higher for
      treatment of acne scarring than for photoaging. Overall degree of improvement on
      a 1-10 scale was 5.4 for acne scarring and 3.8 for wrinkling. CONCLUSION:
      Nonablative treatment with the 1,320 nm Nd:YAG laser induced significant patient
      reported improvement in both acne scarring and photoaging. The majority of
      patients reported satisfaction with the degree of improvement.

PMID- 16640678
TI  - Erbium:YAG laser-assisted preparation of a combined dermal/full thickness
      sandwich skin graft.
AB  - BACKGROUND: Skin grafting is a common procedure to close defects after tumor
      resection. However, delicate areas such as the heel or the sole of the foot can
      be closed with a specially designed graft as described in this article.
      OBJECTIVE: To describe a surgical technique by means of erbium:YAG laser-assisted
      preparation of a combined dermal/full-thickness sandwich skin graft that
      facilitates the closure of defects, especially at mechanically stressed anatomic
      sites. METHODS: Tumor defects on the sole of the foot of 28 patients were closed
      with a new dermal/full-thickness sandwich skin graft. To obtain this special
      graft, half of a full-thickness skin graft twice the size of the wound defect was
      deepithelialized with an erbium:YAG laser. After complete defatting of the
      transplant, the deepithelialized part was folded beneath the full-thickness part
      (upside down) resulting in a sandwich graft, enabling contact of the papillary
      dermis with the wound surface. Graft results were graded as excellent when more
      than 75%, good if 50-75%, fair if 25-50%, and poor if less than 25% of the
      transplant healed. RESULTS: Results were graded as excellent in 32%, good in 54%,
      fair in 11%, and poor in 3% of the patients. Total graft loss was experienced in
      1 of 28 patients. Complications such as bulky margins or infection were
      encountered in 14% of the patients. CONCLUSION: The laser-assisted preparation of
      the combined dermal/full-thickness sandwich skin graft is a new technique that
      facilitates the closure of defects in delicate anatomic locations with high
      mechanical stress like the plantar sole.

PMID- 16640679
TI  - In vivo effect of carbon dioxide laser-skin resurfacing and mechanical abrasion
      on the skin's microbial flora in an animal model.
AB  - BACKGROUND: Although beam-scanning carbon dioxide (CO2) lasers have provided a
      highly efficient tool for esthetic skin rejuvenation there has been no
      comprehensive animal studies looking into microbial skin changes following CO2
      laser skin resurfacing. OBJECTIVE: To evaluate the in vivo effects of CO2 laser
      skin resurfacing in an experimental rat model in comparison with mechanical
      abrasion on the skin microbial flora. METHODS: Four separate cutaneous sections
      of the right dorsal surface of 10 Wistar rats were treated with a CO2 laser,
      operating at 18 W and delivering a radiant energy of 5.76 J/cm2, while mechanical
      abrasions of the skin were created on four sections of the left dorsal surface
      using a scalpel. Samples for culture and biopsies were obtained from the skin
      surfaces of the rats on day 1 of application of the CO2 laser or mechanical
      abrasion, as well as 10, 30, and 90 days after the procedure. The presence of
      four microorganisms (staphylococci, streptococci, diphtheroids, and yeasts) was
      evaluated as a microbe index for the skin flora, and colony counts were obtained
      using standard microbiological methods. RESULTS: Skin biopsy specimens, following
      CO2 laser treatment, initially showed epidermal and papillary dermal necrosis and
      later a re-epithelization of the epidermis as well as the generation of new
      collagen on the upper papillary dermis. The reduction in microbial counts on day
      1 of the CO2 laser-inflicted wound was statistically significant for
      staphylococci and diphtheroids compared with the baseline counts (p=.004 and
      p<.001, respectively), and for staphylococci, diphtheroids, and yeasts compared
      with the scalpel-inflicted wound on the same day (p=0.029, p<.001, and p=.030,
      respectively). CONCLUSIONS: Skin resurfacing using CO2 lasers considerably
      reduces microbial counts of most microorganisms in comparison with either normal
      skin flora or a scalpel-inflicted wound. This might contribute to the positive
      clinical outcome of laser skin resurfacing.

PMID- 16640680
TI  - Repeated treatment protocols for melasma and acquired dermal melanocytosis.
AB  - BACKGROUND AND OBJECTIVE: Melasma and acquired dermal melanocytosis (ADM;
      acquired bilateral nevus of Ota-like macules) are both seen most commonly
      symmetrically on the face of women with darker skin and are also known as
      difficult conditions to treat. METHODS: Our topical bleaching protocol with 0.1
      to 0.4% tretinoin gel and 5% hydroquinone was performed repeatedly (1-3 times)
      for melasma (n=163), and a combination treatment with topical bleaching and Q
      switched ruby (QSR) laser was performed repeatedly (1-3 times) for ADM (n=62).
      RESULTS: There is a significant correlation between clinical results (clearance
      of pigmentation) and the number of sessions in both melasma (p=.019) and ADM
      (p<.0001). CONCLUSION: The repeated treatment protocol for melasma and ADM showed
      successful clinical results compared with conventional ones, and they may be
      applied to other pigment conditions. It may be better that epidermal and dermal
      pigmentations are treated separately, especially in dark-skinned people who are
      more likely to suffer postinflammatory hyperpigmentation after inflammation
      inducing therapies.

PMID- 16640681
TI  - Whitening effect of salicylic acid peels in Asian patients.
AB  - BACKGROUND: Patients with skin of color demand treatment modality suitable for
      their skin. Salicylic acid peel has effectiveness for both of acne and
      postinflammatory hyperpigmentation that are common in patients with skin of
      color. OBJECTIVE: To assess the whitening effect of salicylic acid peels in Asian
      patients with acne objectively by the colorimetric method. METHODS: Twenty-four
      healthy adult patients with acne participated voluntarily in the study. Any other
      systemic and topical acne treatments were prohibited. They had undergone full
      face peels with 30% salicylic acid in absolute ethanol bi-weekly for 3 months.
      Colorimetric changes of the face were recorded with reflectance
      spectrophotometer. RESULTS: Paired comparisons with pretreatment CIE L*a*b*
      showed abrupt descent of L* value after first peel (p=.0286). Then there was
      continued increase of mean L* value, even though the final L* value did not reach
      a statistically significant level. The mean a* value decreased continually, and
      the a* values recorded after the second, third, fourth, fifth, and final peel
      showed significantly lowered levels (p=.0027, .0005, <.0001, <.0001, <.0001).
      CONCLUSION: Salicylic acid peels are beneficial in whitening the face of Asian
      patients with acne. The whitening effect would be an important factor in choosing
      the superficial peeling agent for them.

PMID- 16640682
TI  - Effect of serial microdermabrasion on the ceramide level in the stratum corneum.
AB  - BACKGROUND: Microdermabrasion has become a popular method for superficial
      resurfacing of the epidermis. Despite the popularity of this technique, few
      studies have examined changes in the levels of lipids (especially ceramide) in
      the stratum corneum following microdermabrasion. OBJECTIVE: To assess and analyze
      changes in the ceramide level in the stratum corneum during the course of serial
      aluminum oxide microdermabrasion. METHODS: Eleven healthy volunteers were
      enrolled in this study. Each participant underwent microdermabrasion once a week
      for 5 weeks. Following each procedure, the ceramide level in the resulting
      epidermal scales was measured. RESULTS: A statistically significant increase in
      the ceramide level in the stratum corneum was observed following the first and
      second microdermabrasion sessions. After the third and fourth sessions, the
      ceramide level returned to baseline. CONCLUSION: The results suggest that
      microdermabrasion alters the epidermal ceramide level. These findings provide the
      first evidence of alterations in the lipid barrier following microdermabrasion.

PMID- 16640683
TI  - Successful treatment of earlobe keloids with imiquimod after tangential shave
      excision.
AB  - BACKGROUND: The treatment of earlobe keloids has historically been suboptimal;
      characterized by discomfort, poor response, and high rates of recurrence. Keloids
      are characterized by increased fibroblast activity in the setting of an altered
      cytokine profile. OBJECTIVE: To investigate whether topical imiquimod 5% cream
      applied postoperatively after tangential excision can prevent recurrence of
      earlobe keloids. METHODS AND MATERIALS: Four patients with a total of eight large
      pedunculated earlobe keloids (five of which were recurrent lesions) were treated
      with debulking by tangential shave excision followed by daily application of
      imiquimod 5% cream for 6 weeks. RESULTS: At 6 and 12 months post-treatment there
      was an excellent cosmetic result and no evidence of recurrence in any of the
      lesions. Patients with keloids that were itchy and painful were completely
      asymptomatic at the conclusion of the study. CONCLUSION: In this pilot study,
      imiquimod 5% cream following tangential shave excision was efficacious for the
      treatment of earlobe keloids. Further study is warranted to confirm the utility
      of imiquimod 5% cream in the treatment of earlobe keloids, as illustrated herein.

PMID- 16640684
TI  - Suction blister epidermal grafting for management of eyelid vitiligo: special
      considerations.
AB  - BACKGROUND: Suction blister epidermal grafting is an established technique for
      the treatment of resistant and stable vitiligo especially over small and
      cosmetically important areas like the face. However, certain areas, such as lips
      and eyelids, require special considerations because of their anatomic
      peculiarities. PATIENTS AND METHODS: The current study was carried out on six
      patients of stable eyelid vitiligo, not responding to medical treatment. Suction
      blister was obtained from the thigh using the suction apparatus and the roof was
      grafted on to the dermabraded eyelid. Certain precautions were taken during the
      procedure, which will be highlighted in the current study. RESULTS: Response was
      excellent in all the patients in 3 to 6 months, with no complications.
      CONCLUSIONS: If carried out properly, suction blister technique is the procedure
      of choice for cosmetically important sites like eyelids.

PMID- 16640685
TI  - En bloc excision of proximal nail fold for treatment of chronic paronychia.
AB  - BACKGROUND: Chronic paronychia is a very recalcitrant dermatosis, which is
      particularly prevalent in housewives. Medical treatment for this condition is
      unsatisfactory in a significant number of cases. Surgical approach forms an
      important part of management, however, this area has received little attention.
      Various surgical approaches have been tried in the past but a comparative
      analysis has not been attempted. OBJECTIVES: The present study aims at assessing
      the efficacy of en bloc excision of proximal nail fold (PNF). Moreover, a
      comparative analysis has been undertaken to assess whether or not simultaneous
      nail plate avulsion improves the treatment outcome. METHODS: Thirty patients of
      chronic paronychia with nail plate irregularities were randomly divided into two
      treatment groups (15 patients each). After a detailed evaluation, en bloc
      excision of PNF with or without nail plate removal was performed. Postoperative
      measures were advised and the patients were kept under regular follow-up
      thereafter. Assessment of postoperative complications was also performed.
      RESULTS: Twelve patients in group I and 13 patients in group II completed the
      treatment protocol. Of these, 70% of patients were cured in group II (en bloc
      excision with nail avulsion) whereas only 41% were cured in group I (en bloc
      excision without nail avulsion). CONCLUSION: En bloc excision of the PNF is a
      useful method in recalcitrant chronic paronychia. Simultaneous avulsion of the
      nail plate improves the surgical outcome. Strict avoidance of irritant exposure
      is necessary to ensure complete treatment and prevent recurrence.

PMID- 16640686
TI  - Narrow elliptical skin excision and cartilage shaving for treatment of
      chondrodermatitis nodularis.
AB  - BACKGROUND: Surgical excision remains the hallmark of therapy for
      chondrodermatitis nodularis chronica (CNC). Although excision is generally
      successful, recurrence at the edge of the excised nodule is well recognized.
      OBJECTIVE: To analyze the clinical features and the recurrence rate of patients
      with CNC treated with elliptical excision of the papule and removal of the
      underlying cartilage. DESIGN: Seventy-four outpatients with CNC, 52 men and 22
      women, were retrospectively analyzed. A narrow elliptical excision of the papule
      followed by a slice of the underlying cartilage were carried out with local
      anesthetic. Cartilage spikes were trimmed carefully shaping a smooth contour from
      the normal helical rim to the defect. RESULTS: Good cosmetic results were
      obtained in all patients. The median follow-up for helical and antihelical
      lesions were 54 and 50 months, respectively. The global recurrence rate was 13.5%
      and ranged from 10.6 to 37.5% for helical and antihelical lesions, respectively.
      CONCLUSIONS: We recommend this surgical procedure because it has been shown to be
      as efficient as other methods and probably faster to perform.

PMID- 16640687
TI  - Does transferred fat retain properties of its site of origin?

PMID- 16640688
TI  - Articaine: an effective adjunctive local anesthetic for painless surgery at the
      depth of the muscular fascia.
AB  - BACKGROUND: Articaine is a unique amide anesthetic that contains a thiophene ring
      and an additional ester group. The rapid diffusion and enhanced tissue
      penetrating properties of articaine enable its use for infiltrative anesthesia.
      OBJECTIVE: To describe the effective use of articaine as an adjuvant local
      anesthetic for surgical excisions requiring dissection at the level of the
      muscular fascia. METHODS AND MATERIALS: We discuss the successful adjunctive use
      of articaine to provide effective infiltrative anesthesia of muscular fascia. We
      review the composition, the pharmacologic properties, and the safety profile of
      articaine. RESULTS: Adjuvant local anesthesia using articaine results in painless
      surgery at the level of the muscular fascia without any perioperative
      complications. CONCLUSION: Articaine is not only well tolerated but also rapidly
      effective for anesthesia in the fascial plane of the trunk and extremities. We
      recommend it be considered as an adjunctive local anesthetic for consistently
      painless cutaneous surgery near the muscular fascia.

PMID- 16640689
TI  - "Running pleated" suture technique opposes wound edges of unequal lengths.
AB  - BACKGROUND: Cutaneous advancement flaps, such as the T-plasty or H-plasty, are
      commonly used in order to relocate standing cones away from critical structures.
      In this process, what would have been the tips of a standard elliptical closure
      are displaced laterally as Burrow's triangles. This method creates additional
      terminal incision lines, perpendicular to the force vector of the flap.
      OBJECTIVE: To describe a suture technique commonly employed in our practice that
      eliminates the need for such Burrow's triangles, hence minimizing suture lines
      and enhancing cosmesis. MATERIALS AND METHODS: Through the described "running
      pleated" suture technique, excess tissue created by flap advancement is
      distributed equally along the entire length of the incision. RESULTS: All
      patients did well postoperatively with excellent wound healing and superior
      cosmetic outcomes. CONCLUSION: The "running pleated" suture technique obviates
      the need for large, laterally displaced Burrow's triangles that are normally
      created during the construction of flaps such as the T-plasty and H-plasty and
      can be a powerful tool in the armamentarium of any dermatologic surgeon.

PMID- 16640690
TI  - Triple advancement flap to repair an upper lip defect.

PMID- 16640691
TI  - One-stage reconstruction following complete alar loss.

PMID- 16640692
TI  - Dermoscopic differentiation of a superficial basal cell carcinoma and squamous
      cell carcinoma in situ.

PMID- 16640693
TI  - Clinical conference: management of rare events following dermal fillers--focal
      necrosis and angry red bumps.

PMID- 16640694
TI  - Atypical fibroxanthoma: review of the literature and summary of 13 patients
      treated with mohs micrographic surgery.

PMID- 16640695
TI  - Basal cell carcinoma associated with orbital invasion: clinical features and
      treatment options.

PMID- 16640696
TI  - Skin angiosarcoma arising in an irradiated breast: case-report and literature
      review.
AB  - BACKGROUND: Angiosarcoma (AS) is a rare, invasive malignancy originating from
      endothelial cells caused by many different clinical situations. AS following
      radiotherapy for breast cancer after conservative surgery is a rare but well
      known association. OBJECTIVE: The aim of this article is to describe a case of AS
      after breast conserving surgery and to review the literature to date. RESULTS: We
      report the case of an 84-year-old woman who developed AS four years after she was
      subjected to quadrantectomy for invasive ductal cancer, followed by 30 tangent
      field radiotherapy sessions. She presented with a one-month history or red
      papular skin eruptions on the operated breast. Skin lesions were submitted for
      biopsy, and they were positive for AS. The patients was subjected to surgical
      excision of the remaining breast including all AS lesions. She is alive with no
      evidence of disease after 10 months follow-up. CONCLUSION: Post-radiotherapy AS
      is rare neoplasm, but it should be considered in the case of patients with red
      lesions after breast conserving surgery and adjuvant radiotherapy.

PMID- 16640697
TI  - Dermatofibrosarcoma protuberans: a partial response to imatinib therapy.

PMID- 16640698
TI  - Lasers may induce terminal hair growth.

PMID- 16640699
TI  - Masks do double duty.

PMID- 16640700
TI  - Experience with keloids after excision and application of 5% imiquimod cream.

PMID- 16640701
TI  - Recurrence of nonmelanoma skin cancer after post-mohs margin tissue evaluation
      with permanent histopathologic sections.

PMID- 16640702
TI  - Assessment of the tilting properties of the human mitral valve during three main
      phases of the heart cycle: an echocardiographic study.
AB  - RATIONALE AND OBJECTIVES: In experimental models of the left heart, the mitral
      valve (MV) is commonly implanted perpendicular to a central axis of the apex/MV.
      To adapt this to a more correct anatomical model, as well as for further studies
      of the left ventricle, we created a database of implantation angles of the MV and
      annulus during three main phases of the heart cycle, based on standard cardiac
      ultrasound measurements. MATERIALS AND METHODS: Twenty-eight patients were
      studied with the standard cardiac ultrasound equipment. From the apical echo
      window, an anteroposterior (AP) plane and a perpendicular commisure-commisure
      (CC) plane were generated during three critical moments in the heart cycle:
      systole (S); diastole early filling (E); and diastole late filling (A). In both
      planes, the angles between the annular plane and each mitral leaflet, as well as
      the angle between a theoretical longitudinal axis through the apex and center of
      the MV orifice and the mitral annulus plane, were measured with a custom-made
      application of Matlab R14. RESULTS: We observed an inclination of the angle
      mitral annulus/central left ventricle axis, with its lowest point in the
      direction of the aortic valve (AP plane) of 85 degrees+/-7 degrees in systole
      (S), 88 degrees+/-8 degrees in early diastole (E), and 88 degrees+/-7 degrees in
      late diastole (A). In the CC plane, we observed an almost horizontal implantation
      of 91 degrees+/-5 degrees in systole (S), 91 degrees+/-8 degrees in early
      diastole (E), and 91 degrees+/-7 degrees in late diastole (A).

PMID- 16640703
TI  - Hepatopulmonary syndrome and right ventricular diastolic functions: an
      echocardiographic examination.
AB  - AIM: Liver functions are affected in the course of cardiac diseases, and
      similarly, liver diseases affect cardiac functions. Many studies in the
      literature have shown that left ventricular systolic and/or diastolic dysfunction
      may develop during chronic liver disease. However, there are limited studies
      investigating right ventricular functions during chronic liver diseases. METHODS:
      A total of 84 patients who had no systolic and/or diastolic dysfunction in the
      left ventricle (LV) were evaluated; 46 patients with liver cirrhosis; 10 (21.74%)
      cirrhotic patients with hepatopulmonary syndrome (HPS) (group 1), 36 (78.26)
      cirrhotic patients without HPS (group 2), and 38 healthy individuals were treated
      as control. RESULTS: Right ventricular diastolic dysfunction was determined in
      all patients of group 1 (100%), 26 of group 2 (72.22 %), and 4 of the controls
      (10.52%) (P<0.05). Tricuspid deceleration time (dt) was significantly different
      between the groups (P<0.05). In addition, right atrium (RA) diameters, right
      ventricle (RV) diameters, and RV wall thickness were significantly different
      between the groups (P<0.05). Pulmonary artery pressure (P<0.05) and pulmonary
      vascular resistance (P<0.05) were also seen to be higher in group 1 than those in
      group 2 and control group. CONCLUSIONS: Right ventricular diastolic dysfunction
      rate is high in chronic liver diseases. In the presence of HPS, right ventricular
      diastolic dysfunction is more remarkable in patients than those without HPS.
      Right ventricular diastolic dysfunction may result in dilatation and hypertrophy
      in the right heart.

PMID- 16640704
TI  - Coronary flow velocity reserve measurement in three major coronary arteries using
      transthoracic Doppler echocardiography.
AB  - BACKGROUND: Measurement of the coronary flow velocity reserve (CFVR) by
      transthoracic Doppler echocardiography (TTDE) has been reported to be useful for
      the noninvasive assessment of significant coronary artery stenosis or myocardial
      ischemia. The purpose of this study was to evaluate the value of this method in
      three major coronary arteries for detecting myocardial ischemia in the clinical
      setting. METHODS: We studied 89 consecutive patients who were referred to our
      outpatient clinic because of chest pain. We measured CFVR using TTDE in three
      major coronary arteries. We defined CFVR<2.0 in at least one vessel as being
      positive for myocardial ischemia. The accuracy of CFVR measurements for detecting
      myocardial ischemia was determined in comparison with exercise thallium-201 (Tl
      201) single photon emission computed tomography (SPECT) as a reference standard.
      RESULTS: CFVR in at least one vessel was successfully measured in 87 of 89
      patients (98%). The sensitivity and specificity of CFVR<2.0 in at least one
      coronary vessel, in any of the coronary territories, was 86% and 89%,
      respectively. In terms of assessing myocardial ischemia in each coronary artery
      territory, the agreement between CFVR<2.0 and Tl-201 SPECT for the left anterior
      descending coronary artery, the posterior descending coronary artery, and the
      left circumflex coronary artery territories was 95%, 81%, and 73%, respectively.
      CONCLUSION: Noninvasive CFVR measurement by TTDE may be useful for detecting
      myocardial ischemia, as well as for identifying ischemic territories in the
      clinical setting.

PMID- 16640705
TI  - Differentiation of left ventricular diastolic dysfunction, identification of
      pseudonormal/restrictive mitral inflow pattern and determination of left
      ventricular filling pressure by Tei index obtained from tissue Doppler
      echocardiography.
AB  - BACKGROUND: Tei index obtained from tissue Doppler echocardiography (TDE-Tei
      index) has an inherent advantage of recording its systolic and diastolic
      components simultaneously on the same cardiac cycle. The aims of this study are
      to evaluate whether TDE-Tei index also exerts a correlation with left ventricular
      (LV) systolic and diastolic function and filling pressure and to see whether it
      can effectively identify the pseudonormal/restrictive mitral filling pattern.
      METHODS: Echocardiographic examination was performed in 243 consecutive patients.
      These patients were classified into three groups as normal, abnormal relaxation,
      and pseudonormal/restrictive groups according to the transmitral E/A-wave
      velocity (E/A), early diastolic velocity of lateral mitral annulus (Ea) and E/Ea.
      RESULTS: Standard Doppler indices of LV filling such as E, A, E/A, and E-wave
      deceleration time had a bimodal distribution, but Ea decreased and E/Ea and TDE
      Tei index increased progressively with worsening of LV diastolic function. The
      sensitivity and specificity of TDE-Tei index>0.51 in the discrimination of
      pseudonormal/restrictive filling pattern were 85% and 96%, respectively. After
      stepwise multiple linear regression analysis, TDE-Tei index had a significant
      negative correlation with Ea (beta=-0.296, P<0.001) and ejection fraction (beta=
      0.293, P<0.001) and positive correlation with E/Ea (beta=0.235, P=0.001).
      CONCLUSIONS: TDE-Tei index increased with worsening of LV diastolic function and
      can effectively identify the pseudonormal/restrictive mitral inflow pattern. It
      also correlated with the echocardiographic parameters of LV systolic and
      diastolic function and filling pressure. It suggests that TDE-Tei index is a
      simple and feasible marker in assessing global LV function.

PMID- 16640706
TI  - Maximum longitudinal relaxation velocity of the left ventricle: its clinical
      value and relationship with NT-proBNP plasma levels in heart failure.
AB  - BACKGROUND: M-mode recordings of the mitral annulus to measure the maximum
      ascending velocity during early diastole as an expression of maximum longitudinal
      relaxation velocity of the left ventricle (RVm) can be used as an index of left
      ventricular (LV) diastolic function. The purpose of this study was to determine
      the relationship of RVm with LV functional parameters in patients with heart
      failure, with N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels,
      and with their functional classification. METHODS AND RESULTS: RVm was recorded
      in 97 patients by M-mode echocardiography. Patients were classified according to
      the New York Heart Association (NYHA) and the concentration of NT-proBNP was
      determined. Patients with ejection fraction (EF)>40 showed a significant
      correlation between RVm and mitral annulus motion (MAM), mitral flow propagation
      velocity, E/A, age, deceleration time (DT), and NT-proBNP. In patients with
      EF<or=40, RVm correlated significantly with MAM, EF, and NT-proBNP. RVm values
      were higher in NYHA class I compared to II and III, P<0.0001. CONCLUSIONS: RVm
      correlates better with functional parameters in patients with EF>40, though its
      relationship with NT-proBNP both in patients with EF>or<or=40 is to be
      highlighted. Correlation between RVm and NT-proBNP is influenced by age, EF, and
      E/A, whereas in patients with EF>40 it is influenced only by age. RVm values
      showed a significant decrease in NYHA class II and III.

PMID- 16640707
TI  - Pre- and postoperative quantitation of right ventricular tissue Doppler
      velocities in infants with hypoplastic left heart syndrome.
AB  - BACKGROUND: The purpose of this study was to use tissue Doppler imaging (TDI) to
      serially quantitate initial and preoperative right ventricular (RV) TDI
      velocities and compare them to postoperative RV TDI velocities as measures of RV
      function in newborns with hypoplastic left heart syndrome (HLHS). METHODS: Twelve
      consecutive patients were prospectively studied with diagnosis of HLHS. Systolic
      (Sw) and early diastolic (Ew) velocities were recorded at the tricuspid annulus
      and the ventricular septum at (1) admission, (2) immediately preoperative, and
      (3) during recovery. All patients were treated preoperatively with prostaglandins
      (PGE). Velocities were compared using repeated measure analysis of variance.
      RESULTS: Mean age at diagnosis was 1 day (0-4 days). Time from diagnosis to
      surgery was 4 days (1-9 days), age at surgery 5.3 days (2-10 days), and time from
      surgery to postoperative echo 12.3 days (5-19 days). Tricuspid annular and septal
      systolic velocities increased from admission to preoperative. Both tricuspid Sw
      and Ew and septal Sw velocities decreased postoperatively. No significant changes
      occurred in the ventricular septal diastolic (Ew) velocities from admission to
      preoperative. CONCLUSION: These data indicate that following the institution of
      PGE and initial medical and ventilatory management, there is an increase in RV
      annular and septal systolic velocities from the initial to the preoperative
      period and that these indices as well as RV annular diastolic velocities decline
      significantly postoperatively. Initial septal diastolic velocities were severely
      abnormal and did not significantly change pre- and postoperatively. These data
      may have significance for both postoperative and subsequent long-term RV
      function.

PMID- 16640708
TI  - The impact of coronary artery disease risk factors on intravascular ultrasound
      derived morphologic indices of human coronaries.
AB  - OBJECTIVE: The relationship of intravascular ultrasound (IVUS)-derived
      measurements of atherosclerotic plaque to various coronary artery disease (CAD)
      risk factors is not well known. The purpose of this study was to examine the
      relationship of percent coronary luminal stenosis by IVUS to other IVUS measures
      of CAD, as well as the relationship of common IVUS measures of CAD to traditional
      CAD risk factors. We hypothesized that one or more IVUS measures of CAD might
      relate more strongly to CAD risk factors than does percent luminal coronary
      stenosis. METHODS: The records of 897 consecutive patients (57% men, mean age 62
      years) who underwent IVUS investigation of their coronary arteries from 1996
      through 2001 were retrospectively reviewed. IVUS was performed using a 20-MHz
      probe (Jomed, Rancho Cordoba, CA) and a manual pull-back technique to image the
      coronary arteries. Coronary artery remodeling ratio-i.e., the ratio of coronary
      lesion external elastic membrane cross-sectional area (EEM CSA) to proximal
      reference artery EEM CSA; plaque burden-i.e., plaque plus media CSA divided by
      EEM CSA; calcium arc; and percent stenosis of luminal cross-sectional area were
      measured by a single reader. RESULTS: Percent area stenosis, the most commonly
      used IVUS parameter, did not correlate with the other three IVUS-derived
      parameters, nor was it related to any of the CAD risk factors considered. In
      contrast, remodeling ratio was directly correlated with plaque burden (r=0.22,
      P<0.001), but inversely related to calcium arc (r=-0.13, P=0.01). IVUS plaque
      burden was significantly correlated with male gender (P<0.0001) and diabetes
      mellitus (DM) (P=0.003). In multivariate analyses including age, gender, and CAD
      risk factors, plaque burden was significantly associated with age, male gender,
      and DM, but not with chronic renal failure, hypertension, or
      hypercholesterolemia. The multivariate model also revealed that the calcium arc
      was significantly associated with male gender and age. These IVUS findings
      provide anatomic documentation that the traditional CAD risk factors relate more
      strongly to plaque burden than to percent coronary arterial luminal narrowing.

PMID- 16640709
TI  - Bedside percutaneous transseptal mitral commissurotomy under sole transthoracic
      echocardiographic guidance in a critically ill patient.
AB  - Percutaneous transvenous mitral commissurotomy is an effective and safe
      alternative to surgical treatment, in selected patients of rheumatic mitral
      stenosis. It is usually performed under fluoroscopic guidance in the
      catheterization laboratory. We report the successful performance of emergency
      mitral commissurotomy by the Inoue balloon at bedside under sole transthoracic
      echocardiographic guidance in a critically ill patient.

PMID- 16640710
TI  - Echocardiographic diagnosis of air embolism associated with central venous
      catheter placement: case report and review of the literature.
AB  - Transthoracic echocardiography (TTE) is a valuable tool in the evaluation of
      patients with suspected air embolism. This report describes the presentation and
      evaluation of a critically ill woman with spontaneous air embolism occurring
      during a central venous catheter replacement. Bedside TTE established the
      diagnosis of air embolism, allowing prompt initiation of appropriate therapy.
      This case report highlights this uncommon but potentially life-threatening
      complication of central line placement and the utility of echocardiography in its
      evaluation.

PMID- 16640711
TI  - Methemoglobinemia following transesophageal echocardiography: a case report and
      review.
AB  - Benzocaine (ethyl aminobenzoate) is a topical anesthetic widely used for
      oropharyngeal anesthesia prior to transesophageal echocardiography (TEE). Topical
      anesthetics have been reported to cause methemoglobinemia, but this adverse event
      is extremely rare and has not been listed as one of the possible complications of
      TEE. However, recently the number of published case reports of TEE-associated
      methemoglobinemia has increased. Since its first description in 1950, 65 cases of
      methemoglobinemia have been reported including a recent report of five cases from
      a single center. Physicians who are not familiar with the association of TEE with
      benzocaine-induced methemoglobinemia may not recognize the idiosyncratic and
      often nonspecific characteristic of this condition. Recognition is critical,
      however, since left untreated methemoglobinemia can lead to cardiopulmonary
      compromise, neurological sequelae, and even death. The current report documents
      an additional case of TEE-associated methemoglobinemia from a high-volume (8000
      cases /year including 400-450 TEE/year) echo lab. A review of the literature
      suggests that this complication may be more prevalent, than generally
      appreciated. This case report emphasizes the importance of appropriate dose,
      recognition, and the treatment of this entity to cardiologists performing TEE.

PMID- 16640712
TI  - A different intracardiac mass: retained sponge.
AB  - We report a case involving a surgical sponge retained following an aortic valve
      replacement. The surgical sponge was placed into the left ventricle to protect
      calcified debris from falling down into the left ventricular cavity. However, the
      sponge was forgotten and left inside the patient. We identified the retained
      surgical sponge by transesophageal echocardiography, which was performed because
      of a difficulty in weaning the patient from the cardiopulmonary bypass.

PMID- 16640713
TI  - Intracardiac echo guided valvuloplasty of a stenotic tricuspid prosthetic valve
      in a patient with idiopathic hypereosinophilic syndrome.
AB  - A 52-year-old male with idiopathic hypereosinophilic syndrome (HES) was
      transferred to our institution following the development of acute respiratory
      failure and shock. He had previously undergone tricuspid valve replacement with
      bioprosthetic valves on two occasions: the initial surgery for severe native
      tricuspid valve stenosis and the redo surgery for severe prosthetic valve
      stenosis and regurgitation. Conventional imaging assessment using
      transoesophageal echocardiography was suboptimal and comprehensive assessment of
      prosthetic valve function was aided by the use of intracardiac echocardiography
      (ICE). ICE provided high quality 2D imaging of the prosthesis demonstrating
      thrombus-like material coating the inner surfaces of the prosthetic valve stents
      effectively forming a tunnel-like obstruction. Unusual hemodynamics secondary to
      severe tricuspid stenosis were demonstrated by CW Doppler with intermittent
      "signal fusion" resulting from blunted respiratory variation in the markedly
      elevated right atrial pressure relative to right ventricular pressure. Successful
      balloon valvuloplasty was performed with ICE proving highly valuable in guiding
      balloon position as well as monitoring the efficacy of the subsequent inflations.

PMID- 16640714
TI  - Left ventricular aneurysm in a five-week-old child.
AB  - Ventricular aneurysms in the pediatric population are rare and no standardized
      method of treatment exists. We present a case of left ventricular (LV) aneurysm
      in an infant, 5 weeks after a balloon aortic valvuloplasty for congenital aortic
      stenosis.

PMID- 16640715
TI  - Technical aspects of diastology: why mitral inflow and tissue Doppler imaging are
      the preferred parameters?
AB  - Doppler methods for assessing left ventricular (LV) diastolic function have
      increased in number and complexity. However, time constraints may prevent
      measurement of all parameters during routine transthoracic echocardiography.
      Therefore, we designed a study to determine which Doppler parameters could be
      most successfully and quickly obtained. The recording success rate and time
      required to record different LV diastolic function parameters were evaluated in
      80 patients. A specific recording protocol was followed by an experienced,
      credentialed sonographer and time intervals to record each parameter were
      measured. In comparison with color Doppler M-mode of LV inflow propagation
      velocities (Vp) and pulmonary venous (PV) flow measurements, transmitral valve
      (MV) flow and tissue Doppler imaging (TDI) of the mitral annulus had the highest
      recording success rate and required the shortest time to record. PV flow and Vp
      took longer to obtain (80.1+/-34.3 sec and 57.1+/-29.1 sec, respectively) than
      did mitral valve inflow (36.3+/-20.7 sec) and mitral valve annular TDI (29.3+/
      18.4 sec for septal and 33.3+/-14.5 sec for lateral). MV flow velocities, Vp, and
      TDI were successfully recorded in virtually all patients (99-100%). In
      comparison, the PV flow velocities and durations were successfully recorded less
      often. The range of success rates for the six PV flow parameters was 49-84%.
      Since MV flow and TDI also have been shown by us to have the lowest interreader
      variability, measurement of these two parameters may be preferred for routine
      clinical evaluation of LV diastolic function in a busy echocardiography
      laboratory.

PMID- 16640716
TI  - Live/real time three-dimensional transthoracic echocardiographic assessment of
      mycotic pseudoaneurysm involving the descending thoracic aorta.
AB  - We describe a patient in whom a mycotic aneurysm involving the distal descending
      thoracic aorta could be definitively diagnosed by live/real time three
      dimensional transthoracic echocardiography.

PMID- 16640717
TI  - Pseudoaneurysm of mitral valve due to severe aortic valve regurgitation.

PMID- 16640718
TI  - Left ventricular outflow tract obstruction due to anomalous attachment of chordae
      tendineae in the subaortic region.

PMID- 16640719
TI  - A rare case of intracardiac thymoma.

PMID- 16640720
TI  - Isolated left ventricular noncompaction: echocardiographic diagnosis.

PMID- 16640721
TI  - Analysis of expressed sequence tags from Rhynchosciara americana salivary glands.
AB  - The diptera Rhynchosciara americana (sciaridae) is an important model organism in
      polyteny and gene amplification research, but up to now a limited amount of data
      regarding DNA sequences and molecular aspects of this species is available.
      Considering the importance of going further on the DNA puffs biological meaning,
      we proposed to generate EST sequences from a DNA library constructed from
      salivary glands. After their categorization in gene ontology terms, they were
      used to construct an 'electronic Northern' that represents a general view of the
      salivary gland metabolic status in an important phase of larval development: the
      spinning of communal cocoon. In this phase occurs the last polytene DNA
      replication cycle concomitantly with the specific loci amplification related to
      protein secretion.

PMID- 16640722
TI  - Immulectin-4 from the tobacco hornworm Manduca sexta binds to lipopolysaccharide
      and lipoteichoic acid.
AB  - Insect C-type lectins function as pattern recognition receptors in innate
      immunity. In the tobacco hornworm Manduca sexta, we have previously isolated
      three C-type lectins named immulectins, which are involved in innate immune
      responses. Here, we report a new member of the immulectin family, immulectin-4
      (IML-4). IML-4 mRNA was detected in the fat body of control larvae and was
      induced in the fat body when larvae were injected with bacteria. Recombinant IML
      4 bound to bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and
      the binding activity was not affected by addition of calcium or EGTA. IML-4
      agglutinated bacteria and yeast, and agglutination of Escherichia coli by IML-4
      was concentration- and calcium-dependent. IML-4 also enhanced haemocyte
      encapsulation and melanization.

PMID- 16640723
TI  - High efficiency site-specific genetic engineering of the mosquito genome.
AB  - Current techniques for the genetic engineering of insect genomes utilize
      transposable genetic elements, which are inefficient, have limited carrying
      capacity and give rise to position effects and insertional mutagenesis. As an
      alternative, we investigated two site-specific integration mechanisms in the
      yellow fever mosquito, Aedes aegypti. One was a modified CRE/lox system from
      phage P1 and the other a viral integrase system from Streptomyces phage phi C31.
      The modified CRE/lox system consistently failed to produce stable germline
      transformants but the phi C31 system was highly successful, increasing
      integration efficiency by up to 7.9-fold. The ability to efficiently target
      transgenes to specific chromosomal locations and the potential to integrate very
      large transgenes has broad applicability to research on many medically and
      economically important species.

PMID- 16640724
TI  - Evidence for a putative antennal clock in Mamestra brassicae: molecular cloning
      and characterization of two clock genes--period and cryptochrome-- in antennae.
AB  - Circadian rhythms are generated by endogenous circadian clocks, organized in
      central and peripheral clocks. An antennal peripheral clock has been demonstrated
      to be necessary and sufficient to generate Drosophila olfactory rhythms in
      response to food odours. As moth pheromonal communication has been demonstrated
      to follow daily rhythms, we thus investigated the occurence of a putative
      antennal clock in the noctuid Mamestra brassicae. From moth antennae, we isolated
      two full-length cDNAs encoding clock genes, period and cryptochrome, which
      appeared to be expressed throughout the body. In the antennae, expression of both
      transcripts was restricted to cells that likely represent olfactory sensory
      neurones. Our results suggest the occurence of a putative antennal clock that
      could participate in the pheromonal communication rhythms observed in vivo.

PMID- 16640725
TI  - Biochemical characterization of Drosophila gamma-glutamyl carboxylase and its
      role in fly development.
AB  - To investigate structure-function relationships in gamma-glutamyl carboxylases,
      the enzyme from Drosophila melanogaster was characterized. Four cysteine residues
      were shown to be important determinants for enzymatic activity. Native Drosophila
      substrates have not yet been identified, but propeptides of human prothrombin and
      factor IX are recognized by the Drosophila enzyme. The presence of the propeptide
      region increased apparent affinity by approximately 200-fold, and mutation of a
      hydrophobic residue of factor IX propeptide (F-16A) decreased carboxylation by
      90%, as in the human enzyme. Substrate recognition appears to be highly conserved
      between the human and Drosophila gamma-glutamyl carboxylases. Inactivation of
      Drosophila gamma-glutamyl carboxylase by non-sense mutations or insertional
      mutagenesis by P-element insertion have no apparent effects on growth and
      fertility under laboratory conditions.

PMID- 16640726
TI  - Frequencies of the pyrethroid resistance alleles of Vssc1 and CYP6D1 in house
      flies from the eastern United States.
AB  - House flies were collected from four dairies in Maine, New York, North Carolina,
      and Florida, where high levels of resistance to permethrin have been documented.
      Regions of two genes, CYP6D1 and Vssc1, having alleles that confer resistance to
      permethrin (and other pyrethroids) were analysed from individuals at each
      collection site. The combinations of resistance alleles for Vssc1 and CYP6D1 were
      highly variable between each state. The resistance allele CYP6D1v1 was found at a
      high frequency (0.63-0.91) at all sites. Individuals homozygous susceptible for
      CYP6D1 were very rare and detected only at the dairy in Maine. In addition to the
      typical Vssc1 mutation responsible for resistance, kdr (L1014F), we also
      identified individuals with a L1014H mutation. Although house flies homozygous
      for the L1014H mutation had a lower level of resistance to permethrin, compared
      to L1014F, the H1014 resistance allele was frequently detected. No individuals
      with the super-kdr allele (M918T + L1014F) were detected from the field
      collections. The intron 3 bp downstream of the kdr mutation was found to be
      extremely variable, providing an opportunity to reconstruct a phylogeny of Vssc1
      alleles. Based on this analysis it appears the kdr-his mutation had multiple
      evolutionary origins, but that the kdr mutation may have had a single origin. The
      impacts of these findings on resistance management are discussed.

PMID- 16640727
TI  - Remarkable substrate-specificity of CYP6AB3 in Depressaria pastinacella, a highly
      specialized caterpillar.
AB  - The parsnip webworm, Depressaria pastinacella, a specialist on two genera in
      Apiaceae, feeds exclusively on the furanocoumarin-containing reproductive
      structures of its host plants. This caterpillar relies principally on cytochrome
      P450-mediated detoxification for coping with the high concentrations of
      furanocoumarins in its diet. A cDNA encoding the furanocoumarin-inducible P450
      CYP6AB3 from this species was coexpressed with house-fly NADPH P450 reductase in
      baculovirus-infected Sf9 cells and tested for binding and metabolism of the six
      furanocoumarins typically encountered in host plant tissues. Only imperatorin and
      bergapten bind in close proximity to the catalytic haem and only imperatorin is
      metabolized (V(max) and K(m) of 2.412 pmol/min per pmol P450 and 94.28 microm,
      respectively). Purification of the imperatorin metabolite by normal phase HPLC
      and characterization of its structure by MS-MS analysis indicate that CYP6AB3
      initially epoxidizes the carbon-carbon pi-bond on the isoprenyl side chain on
      imperatorin. An improved molecular model for the CYP6AB3 protein based on this
      biochemical characterization and the recently defined mammalian CYP3A4 crystal
      structure provides insight into the remarkable substrate specificity of this
      protein.

PMID- 16640728
TI  - Positional cloning of a cyromazine resistance gene in Drosophila melanogaster.
AB  - Cyromazine is an effective insecticide used to control dipteran insects. Its
      precise mode of action is yet to be determined, although it has been suggested
      that it interferes with the hormone system, sclerotization of the cuticle, or
      nucleic acid metabolism. To understand the way in which cyromazine acts, we have
      positionally cloned a cyromazine resistance gene from Drosophila melanogaster.
      Six cyromazine resistance alleles had previously been generated by ethyl
      methanasulphonate treatment. Two of these failed to complement each other and
      here we identify them as having independent non-sense mutations in CG32743, which
      is an ortholog of Smg1 of worms and mammals and encodes a phosphatidylinositol
      kinase-like kinase (PIKK). RNAi experiments confirm that cyromazine resistance
      can be achieved by knocking down CG32743. These are the first cyromazine
      resistant mutations identified at the nucleotide level. In mammals Smg1
      phosphorylates P53 in response to DNA damage. This finding supports the
      hypothesis that cyromazine interferes with nucleic acid metabolism.

PMID- 16640729
TI  - Isolation, endocrine regulation and mRNA distribution of the 3-hydroxy-3
      methylglutaryl coenzyme A synthase (HMG-S) gene from the pine engraver, Ips pini
      (Coleoptera: Scolytidae).
AB  - We isolated a full-length cDNA encoding 3-hydroxy-3-methylglutaryl coenzyme A
      synthase (HMG-S) from the pine engraver beetle, Ips pini (Say), and examined its
      genomic structure. The intron-less gene has a predicted 460 amino acid cytosolic
      protein product with 73% identity to HMG-S from Dendroctonus jeffreyi, and high
      identity (58-64%) with other insect HMG-Ss. Topically applied juvenile hormone
      (JH) III induced HMG-S mRNA levels up to 6.5-fold in both sexes, mostly in the
      anterior midgut, though there were differences between males and females in the
      timing, sensitivity to JH III dose and tissue distribution of HMG-S mRNA. These
      data further validate the coordinate regulation of mevalonate pathway genes for
      de novo isoprenoid pheromone production in bark beetles.

PMID- 16640730
TI  - Co-immunoprecipitation of putative proteins that interact with mosquito
      proliferating cell nuclear antigen.
AB  - We have sequenced cDNAs encoding proliferating cell nuclear antigen (PCNA) from
      Aedes albopictus cells and from Aedes aegypti mosquitoes. The mosquito cDNAs
      contained an open reading frame encoding a 260 amino acid protein with a
      calculated mass of 29.0 kDa and a pI of 4.46. There was a single amino acid
      difference between PCNA proteins from Ae. albopictus and Ae. aegypti. In An.
      gambiae, the PCNA homolog contained 260 residues, and the pcna gene was
      interrupted by a single 67 nucleotide intron in the betaC2 region of the protein.
      A phylogenetic comparison grouped known Dipteran PCNA sequences into two
      clusters, representing the Nematocera and the Cyclorrhapha. PCNA transcripts
      measured 1.1 kb, and were stable, as was PCNA protein. Mosquito PCNA was
      efficiently recognized by a commercially available mouse anti-PCNA monoclonal
      antibody, which coprecipitated 29 kDa and 35 kDa proteins from mosquito cells
      representing different growth states. These results support the feasibility of
      recovering mosquito cell cycle inhibitory proteins by virtue of their interaction
      with PCNA.

PMID- 16640731
TI  - Effects of juvenile hormone on gene expression in the pheromone-producing midgut
      of the pine engraver beetle, Ips pini.
AB  - Juvenile hormone III (JH III) stimulates biosynthesis of the monoterpenoid
      aggregation pheromone component, ipsdienol, in the anterior midgut of the male
      pine engraver beetle, Ips pini (Say). To understand better the hormonal
      regulation of pheromone biosynthesis in this forest pest, and identify JH III
      responsive genes, microarrays were prepared and hybridized to cDNA from midguts
      of JH III-treated beetles. Expression patterns were confirmed by quantitative
      real-time RT-PCR. JH III co-ordinately regulated mevalonate pathway genes and
      many other genes implicated in pheromone biosynthesis. Sex differences in basal
      levels of mevalonate pathway genes were consistent with their role in male
      specific pheromone biosynthesis. This is the first microarray-based study of the
      developmental and hormonal regulation of insect pheromone biosynthesis.

PMID- 16640732
TI  - The mitochondrial genome of the Korean hairstreak, Coreana raphaelis
      (Lepidoptera: Lycaenidae).
AB  - We determined the complete nucleotide sequences of the mitochondrial genome
      (mitogenome) of the Korean hairstreak, Coreana raphaelis (Lepidoptera:
      Lycaenidae). The entire mitochondrial DNA (mtDNA) molecule was 15,314 bp long.
      The C. raphaelis genes were in the same order and orientation as the completely
      sequenced mitogenomes of other lepidopteran species, except for the presence of
      an extra copy of tRNA(Ser)(AGN). High similarity in primary sequence and
      secondary structure between the two tandemly located copies of the tRNA(Ser)(AGN)
      suggest a recent duplication of an original single tRNA(Ser)(AGN). The DHU arm of
      the two copies of tRNA(Ser)(AGN) formed a simple loop as seen in many other
      metazoan mt tRNA(Ser)(AGN). The putative initiation codon for the C. raphaelis
      COI gene appears to be a tetranucleotide, TTAG, found commonly in the sequenced
      lepidopterans. ATPase8, ATPase6, ND4L and ND6 genes, which are next to another
      protein-coding gene at their 3' end all had the sequences potential to form a
      hairpin structure, suggesting the importance of such a structure for precise
      cleavage of the mature protein-coding genes.

PMID- 16640733
TI  - Reversible introduction of transgenes in natural populations of insects.
AB  - The most serious challenge concerning genetically modified insects remains their
      invasion ability. Indeed, transgenic insects often show lower fitness than wild
      individuals, and the transgene does not seem able to spread through a natural
      population without a driving system. The use of remobilizable vectors, based on
      the invading properties of transposable elements, has been frequently suggested.
      Simulations show that this strategy can be efficient. Moreover, if the transgene
      is designed to use transposition machinery already present in the genome, the
      transgene invasion appears to be potentially reversible after a few hundred
      generations, leading to new experimental perspectives.

PMID- 16640734
TI  - Caste-specific cytochrome P450 in the damp-wood termite Hodotermopsis sjostedti
      (Isoptera, Termopsidae).
AB  - Termites are eusocial insects with a well-defined caste system, which is an
      example of polyphenism. This polyphenism is based on hormonally controlled
      differential gene expression. In the damp-wood termite Hodotermopsis sjostedti,
      we induced differentiation into the soldier caste by using juvenile hormone
      analogue treatment. We then investigated specific gene expression, which appeared
      during the hormonal response and triggered caste differentiation, using
      fluorescent differential display. A candidate cDNA sequence with similarity to
      cytochromes P450, CYP6AM1, was characterized and its transcript shown to be
      repressed between 1 and 3 days after hormone treatment. CYP6AM1 was specifically
      expressed in the fat body of pseudergates and soldiers. The putative function of
      this P450 is discussed with respect to the caste differentiation system.

PMID- 16640735
TI  - Pharmaceutical benefits scheme policy: confused and tough on patients.

PMID- 16640736
TI  - Who is at high risk of stroke following transient ischaemic attacks?

PMID- 16640737
TI  - Increasing underrepresentation of elderly patients with advanced colorectal or
      non-small-cell lung cancer in chemotherapy trials.
AB  - BACKGROUND: Elderly patients are underrepresented in chemotherapy trials for
      advanced colorectal cancer (CRC) and non-small-cell lung cancer (NSCLC). However,
      the change in underrepresentation over time has not been documented. AIMS: This
      study aimed to quantify (i) the change in the median age of patients enrolled in
      clinical trials for metastatic CRC and NSCLC between 1982-1991 and 1992-2001
      compared with the general colorectal and lung cancer population, and (ii) the
      proportion of trials with an upper age limit for eligibility. METHODS: A
      retrospective review of data from the Victorian Cancer Registry and all large
      published randomized chemotherapy trials for advanced CRC and NSCLC between 1982
      and 2001 was conducted. RESULTS: The median age of patients with CRC enrolled in
      clinical trials remained constant between the two decades (62.0 and 62.2 years),
      whereas the median age of the CRC population increased from 68.4 to 70.2 years,
      increasing the median age difference from 6.4 to 8.0 years. The median age of
      patients with lung cancer in clinical trials increased from 59.8 to 61.8 years,
      whereas the median age of the lung cancer population increased from 67.4 to 70.4
      years, widening the age difference from 7.6 to 8.6 years. More trials set an
      upper age limit for eligibility in the first decade than in the second decade for
      both CRC (51 vs 29%, P = 0.04) and NSCLC (68 vs 41%, P = 0.03). CONCLUSION:
      International clinical trials for CRC and NSCLC are becoming increasingly
      unsuitable for application to Australian patients because of the increasing age
      discrepancy, despite fewer trials restricting eligibility by age.

PMID- 16640738
TI  - Accuracy of information on medicines in hospital discharge summaries.
AB  - BACKGROUND: At Auckland Hospital, patients have been given handwritten summaries
      on discharge from hospital with a copy posted to the general practitioner. A
      typed summary is often not completed so the list of medicines on the handwritten
      summary needs to be accurate and complete. METHODS: We selected 100 patient
      charts from the general medical service and 100 charts from the general surgical
      service and recorded the medicines on admission, on the inpatient medication
      chart and on the discharge summary. We noted errors in the recording of medicines
      on the discharge summary and rated the severity of errors. RESULTS: Surgical
      patients were discharged on 7.88 (95% confidence interval (CI) 7.40-8.64)
      medicines and medical patients on 8.58 (95% CI 7.87-9.29) medicines. During the
      admission there were 0.59 (95% CI 0.38-0.80) changes to the medicines for the
      surgical patients and 1.70 (95% CI 1.39-2.01) for the medical patients (P <
      0.0001). There were 0.81 (95% CI 0.65-1.02) errors per surgical discharge summary
      and 1.42 (95% CI 1.20-1.67) errors per medical summary (P = 0.006). Four errors
      were graded as having the potential to cause readmission to hospital, 24 as
      potentially serious, 83 as potentially troublesome and 111 as minor. DISCUSSION:
      Error rates were high and although the majority were minor, a number of them had
      the potential to cause serious consequences. There were more medication changes
      in the medical patients and this may contribute to higher error rates in this
      group. There is a need to improve the accuracy of recording medicines on
      discharge summaries. Strategies to improve this problem are discussed.

PMID- 16640739
TI  - 'Free' surfactant in gastric aspirates and bronchoalveolar lavage in children
      with and without reflux oesophagitis.
AB  - AIM: Dipalmitoylphosphatidycholine (DPPC) is the characteristic and main
      constituent of surfactant. Adsorption of surfactant to epithelial surfaces may be
      important in the masking of receptors. The aims of the study were to (i) compare
      the quantity of free DPPC in the airways and gastric aspirates of children with
      gastroesophageal reflux disease (GORD) to those without and (ii) describe the
      association between free DPPC levels with airway cellular profile and capsaicin
      cough sensitivity. METHODS: Children aged <14 years were defined as 'coughers' if
      a history of cough in association with their GORD symptoms was elicited before
      gastric aspirates and nonbronchoscopic bronchoalveolar lavage (BAL) were obtained
      during elective flexible upper gastrointestinal endoscopy. GORD was defined as
      histological presence of reflux oesophagitis. Spirometry and capsaicin cough
      sensitivity test was carried out in children aged >6 years before the endoscopy.
      RESULTS: Median age of the 68 children was 9 years (interquartile range (IQR)
      7.2). Median DPPC level in BAL of children with cough (72.7 microg/mL) was
      similar to noncoughers (88.5). There was also no significant difference in DPPC
      levels in both BAL and gastric aspirates of children classified according to
      presence of GORD. There was no correlation between DPPC levels and cellular
      counts or capsaicin cough-sensitivity outcome measures. CONCLUSION: We conclude
      that free DPPC levels in the airways and gastric aspirate is not influenced by
      presence of cough or GORD defined by histological presence of reflux
      oesophagitis. Whether quantification of adsorbed surfactant differs in these
      groups remain unknown. Free DPPC is unlikely to have a role in masking of airway
      receptors.

PMID- 16640740
TI  - Effect of an education programme on the utilization of a medical emergency team
      in a teaching hospital.
AB  - BACKGROUND: Medical Emergency Teams (MET) have been developed to identify, review
      and manage acutely unwell ward patients. Previous studies have suggested that
      there may be obstacles to the utilization and activation of the MET. AIMS: To
      determine the effect of a detailed education programme on the rate of utilization
      of the MET system 3.5 years after its introduction in a University teaching
      hospital. METHODS: Prospective interventional study involving a detailed
      programme of education, feedback and decision support for nursing and medical
      staff given before, during and after implementation of a MET system. We measured
      the number of MET calls per month for both medical and surgical patients for 109
      250 consecutive admissions to the acute care campus of Austin Health from August
      2000 to June 2004. RESULTS: Overall activation of the MET increased from 25 calls
      per month to a peak of 79 calls per month over the study period (average increase
      of one MET call/month). After standardization for monthly admissions, the
      increase in MET utilization for surgical patients (increase by 1.13 MET/1000
      admissions/month) was 4.9-fold greater than for medical patients (increase by
      0.23 MET/1000 admissions/month; P < 0.0001). At the peak level of activity (April
      2004), the MET was called to review 8.4% of surgical and 2.7% of medical
      admissions (P < 0.0001). CONCLUSIONS: There was a progressive increase in the
      utilization of the MET service in the 3.5 years after implementation, with the
      rate of uptake 4.9 times greater for surgical than for medical patients.
      Sustained uptake of the MET system is possible, but increased utilization may
      take several years to develop. Short-term studies testing the efficacy of the MET
      system are likely to significantly underestimate its effect on reducing adverse
      events. Intensive care unit resource adjustments will become necessary to meet
      increased demand.

PMID- 16640741
TI  - Traditional risk factor assessment does not capture the extent of cardiovascular
      risk in systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is associated with accelerated
      atherosclerosis. However, the degree of endothelial dysfunction and its
      relationship to traditional and novel cardiovascular risk factors have not been
      examined in SLE. METHODS: In a case-control design, 35 patients with clinically
      stable SLE and 35 control subjects matched for age, sex, body mass index and
      smoking status were studied. Arterial elasticity, lipid profile, homocysteine,
      measures of inflammation and oxidative stress were determined. RESULTS: Among
      traditional vascular risk factors, there was a nonsignificant trend towards lower
      blood pressure in the control subjects, whereas low-density lipoprotein (LDL)
      cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L,
      P < 0.001). Patients with SLE had significantly lower small artery elasticity
      (SAE; 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4
      vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs
      494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385
      vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels,
      older age at SLE diagnosis and higher disease damage scores correlated inversely
      with SAE but not traditional risk factors. CONCLUSION: Impaired endothelial
      function as shown by decreased SAE, and an adverse profile of novel
      proatherogenic and prothrombotic vascular disease risk factors were prevalent in
      clinically quiescent SLE. These findings show the vulnerability of patients with
      SLE for atherosclerosis, and emphasize that assessments based on traditional risk
      factors alone may be inadequate.

PMID- 16640742
TI  - Cost-effectiveness of current and optimal treatment for adult asthma.
AB  - BACKGROUND: This article is part of a project to determine the cost-effectiveness
      of averting the burden of disease. We used population data to investigate the
      costs and benefits of allocating resources to optimal treatment for asthma in
      adults, using a burden of disease framework. METHODS: We calculated the
      population burden of asthma in the absence of any treatment as years lived with
      disability (YLD), ignoring the years of life lost. We then estimated the
      proportion of burden averted with current interventions, the proportion that
      could be averted with optimally implemented current evidence-based guidelines and
      the direct treatment cost-effectiveness ratio in dollarA per YLD averted for both
      current and optimal treatment. RESULTS: The direct treatment cost of current
      treatment of adult asthma in Australia was dollar A452 million and averted 25% of
      the burden with a cost-effectiveness ratio of dollar A14 000/YLD averted. Optimal
      treatment and optimal compliance would cost dollar A627 million and avert 69% of
      the burden with a cost-effectiveness ratio of dollar A7000/YLD averted.
      CONCLUSION: Implementation of optimal treatment for asthma is affordable, will be
      more cost-effective and will significantly decrease disability.

PMID- 16640743
TI  - Neuropathic pain: are we out of the woods yet?
AB  - Patients suffering from neuropathic pain continue to pose challenges in clinical
      practice. This descriptive review discusses the continuing debate on the
      definition and concerns about increasing incidence of neuropathic pain. The
      clinical features of neuropathic pain are outlined, and the current understanding
      of the possible mechanisms of neuropathic pain is highlighted. Current management
      strategies are reviewed, and future advances in our understanding of the
      mechanisms, accurate clinical diagnosis and more effective treatment strategies
      are eagerly awaited.

PMID- 16640744
TI  - Does being against euthanasia legislation equate to being anti-euthanasia?
AB  - This study investigated issues raised in qualitative data from our previous
      studies of health professionals and community members, which suggested that being
      opposed to euthanasia legislation did not necessarily equate to being anti
      euthanasia per se. A postal survey of 1002 medical practitioners, 1000 nurses and
      1200 community members was undertaken. In addition to a direct question on
      changing the law to allow active voluntary euthanasia (AVE), four statements
      assessed attitudes to euthanasia with or without a change in legislation.
      Responses were received from 405 doctors (43%), 429 nurses (45%) and 405
      community members (38%). Compared with previous studies there was a slight
      increase in support for a change in the law from medical practitioners, a slight
      decrease in support from community members and almost no change among nurses.
      Different interpretations of the results of the four attitude questions are
      possible, depending on the perspective of the interpreter.

PMID- 16640745
TI  - Rituximab use in systemic lupus erythematosus pneumonitis and a review of current
      reports.
AB  - Rituximab is a chimeric monoclonal antibody specific for human CD20 that causes
      selective transient depletion of the CD20+ B-cell subpopulation. We report the
      first case of systemic lupus erythematosus (SLE) pneumonitis resistant to
      conventional treatments that responded well to rituximab and review current
      reports on the use of rituximab in SLE.

PMID- 16640746
TI  - 'Pseudo' coronary graft stenosis from radial artery spasm.

PMID- 16640747
TI  - On the need for probity when physicians interact with industry.
AB  - Physicians are expected to practice scientifically sound medicine, to be critical
      of industry claims, and to be immune from making clinical decisions biased by
      commercial sponsorship and marketing. The reality, as argued in this article, is
      that much of medical research, in its conduct and reporting, is distorted by
      commercial interests and that physician decision-making remains vulnerable to the
      effects of subliminal commercial promotion which has the potential to create
      conflicts of interest, or perceptions thereof, and undermine public trust.
      Research is presented that may encourage physicians to view recently revised
      Royal Australasian College of Physicians (RACP) guidelines on the ethical
      relationships between the medical profession and industry as an attempt to deal
      with such conflicts in protecting our authority and standing within the
      community.

PMID- 16640748
TI  - Marijuana lung.

PMID- 16640749
TI  - Too quiet on the open access front.

PMID- 16640750
TI  - Why candidates fail: a case of premature examination?

PMID- 16640773
TI  - Molecular characterization of Coxiella burnetii isolates by infrequent
      restriction site-PCR and MLVA typing.
AB  - BACKGROUND: Coxiella burnetii, the causative agent of Q fever, has a wide host
      range. Few epidemiological tools are available, and they are often expensive or
      not easily standardized across laboratories. In this work, C. burnetii isolates
      from livestock and ticks were typed using infrequent restriction site-PCR (IRS
      PCR) and multiple loci variable number of tandem repeats (VNTR) analysis (MLVA).
      RESULTS: By applying IRS-PCR, 14 C. burnetii isolates could be divided into six
      groups containing up to five different isolates. Clustering as deduced from MLVA
      typing with 17 markers provided an increased resolution with an excellent
      agreement to IRS-PCR, and with the plasmid type of each strain. MLVA was then
      applied to 28 additional C. burnetii isolates of different origin and 36
      different genotypes were identified among the 42 isolates investigated. The
      clustering obtained is in agreement with published Multiple Locus Sequence Typing
      (MLST) data. Two panels of markers are proposed, panel 1 which can be confidently
      typed on agarose gel at a lower cost and in any laboratory setting (10
      minisatellite markers with a repeat unit larger than 9 bp), and panel 2 which
      comprises 7 microsatellites and provides a higher discriminatory power.
      CONCLUSION: Our analyses demonstrate that MLVA is a powerful and promising
      molecular typing tool with a high resolution and of low costs. The consistency of
      the results with independent methods suggests that MLVA can be applied for
      epidemiological studies. The resulting data can be queried on a dedicated MLVA
      genotyping Web service.

PMID- 16640774
TI  - Support vector machine for classification of meiotic recombination hotspots and
      coldspots in Saccharomyces cerevisiae based on codon composition.
AB  - BACKGROUND: Meiotic double-strand breaks occur at relatively high frequencies in
      some genomic regions (hotspots) and relatively low frequencies in others
      (coldspots). Hotspots and coldspots are receiving increasing attention in
      research into the mechanism of meiotic recombination. However, predicting
      hotspots and coldspots from DNA sequence information is still a challenging task.
      RESULTS: We present a novel method for classification of hot and cold ORFs
      located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using
      support vector machine (SVM), which relies on codon composition differences. This
      method has achieved a high classification accuracy of 85.0%. Since codon
      composition is a fusion of codon usage bias and amino acid composition signals,
      the ability of these two kinds of sequence attributes to discriminate hot ORFs
      from cold ORFs was also investigated separately. Our results indicate that
      neither codon usage bias nor amino acid composition taken separately performed as
      well as codon composition. Moreover, our SVM based method was applied to the full
      genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of
      recombination rate. We found that the performance of our method for predicting
      cold ORFs is not as good as that for predicting hot ORFs. Besides, we also
      observed a considerable correlation between meiotic recombination rate and amino
      acid composition of certain residues, which probably reflects the structural and
      functional dissimilarity between the hot and cold groups. CONCLUSION: We have
      introduced a SVM-based novel method to discriminate hot ORFs from cold ones.
      Applying codon composition as sequence attributes, we have achieved a high
      classification accuracy, which suggests that codon composition has strong
      potential to be used as sequence attributes in the prediction of hot and cold
      ORFs.

PMID- 16640775
TI  - Study on the clinical application of pulsed DC magnetic technology for tracking
      of intraoperative head motion during frameless stereotaxy.
AB  - BACKGROUND: Tracking of post-registration head motion is one of the major
      problems in frameless stereotaxy. Various attempts in detecting and compensating
      for this phenomenon rely on a fixed reference device rigidly attached to the
      patient's head. However, most of such reference tools are either based on an
      invasive fixation technique or have physical limitations which allow mobility of
      the head only in a restricted range of motion after completion of the
      registration procedure. METHODS: A new sensor-based reference tool, the so-called
      Dynamic Reference Frame (DRF) which is designed to allow an unrestricted, 360
      degrees range of motion for the intraoperative use in pulsed DC magnetic
      navigation was tested in 40 patients. Different methods of non-invasive
      attachment dependent on the clinical need and type of procedure, as well as the
      resulting accuracies in the clinical application have been analyzed. RESULTS:
      Apart from conventional, completely rigid immobilization of the head (type A),
      four additional modes of head fixation and attachment of the DRF were
      distinguished on clinical grounds: type B1 = pin fixation plus oral DRF
      attachment; type B2 = pin fixation plus retroauricular DRF attachment; type C1 =
      free head positioning with oral DRF; and type C2 = free head positioning with
      retroauricular DRF. Mean fiducial registration errors (FRE) were as follows: type
      A interventions = 1.51 mm, B1 = 1.56 mm, B2 = 1.54 mm, C1 = 1.73 mm, and C2 =
      1.75 mm. The mean position errors determined at the end of the intervention as a
      measure of application accuracy were: 1.45 mm in type A interventions, 1.26 mm in
      type B1, 1.44 mm in type B2, 1.86 mm in type C1, and 1.68 mm in type C2.
      CONCLUSION: Rigid head immobilization guarantees most reliable accuracy in
      various types of frameless stereotaxy. The use of an additional DRF, however,
      increases the application scope of frameless stereotaxy to include e.g.
      procedures in which rigid pin fixation of the cranium is not required or desired.
      Thus, continuous tracking of head motion allows highly flexible variation of the
      surgical strategy including intraoperative repositioning of the patient without
      impairment of navigational accuracy as it ensures automatic correction of spatial
      distortion. With a dental cast for oral attachment and the alternative option of
      non-invasive retroauricular attachment, flexibility in the clinical use of the
      DRF is ensured.

PMID- 16640776
TI  - Differential expression of a new isoform of DLG2 in renal oncocytoma.
AB  - BACKGROUND: Renal oncocytoma, a benign tumour of the kidney, may pose a
      differential diagnostic problem due to overlapping phenotype with chromophobe
      renal cell carcinoma or other types of renal cell tumours. Therefore,
      identification of molecular markers would be of great value for molecular
      diagnostics of this tumour type. METHODS: In the current study we applied various
      techniques, including Affymetrix microarray hybridization and semiquantitative RT
      PCR, to identify genes expressed differentially in renal oncocytomas.
      Subsequently, we used RACE and Northern blot hybridization to characterize the
      potential candidates for molecular diagnosis. RESULTS: We have identified new
      isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along
      with the hypothetical gene FLJ37266. The new isoform is specifically upregulated
      in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of
      kidney tumour. CONCLUSION: The new isoform of DLG2 is the promising candidate
      gene for molecular differential diagnostics of renal oncocytoma.

PMID- 16640777
TI  - Differential gene transfers and gene duplications in primary and secondary
      endosymbioses.
AB  - BACKGROUND: Most genes introduced into phototrophic eukaryotes during the process
      of endosymbiosis are either lost or relocated into the host nuclear genome. In
      contrast, groEL homologues are found in different genome compartments among
      phototrophic eukaryotes. Comparative sequence analyses of recently available
      genome data, have allowed us to reconstruct the evolutionary history of these
      genes and propose a hypothesis that explains the unusual genome distribution of
      groEL homologues. RESULTS: Our analyses indicate that while two distinct groEL
      genes were introduced into eukaryotes by a progenitor of plastids, these
      particular homologues have not been maintained in all evolutionary lineages. This
      is of significant interest, because two chaperone proteins always co-occur in
      oxygenic photosynthetic organisms. We infer strikingly different lineage specific
      processes of evolution involving deletion, duplication and targeting of groEL
      proteins. CONCLUSION: The requirement of two groEL homologues for chaperon
      function in phototrophs has provided a constraint that has shaped convergent
      evolutionary scenarios in divergent evolutionary lineages. GroEL provides a
      general evolutionary model for studying gene transfers and convergent
      evolutionary processes among eukaryotic lineages.

PMID- 16640778
TI  - A modular interface of IL-4 allows for scalable affinity without affecting
      specificity for the IL-4 receptor.
AB  - BACKGROUND: Interleukin 4 (IL-4) is a key regulator of the immune system and an
      important factor in the development of allergic hypersensitivity. Together with
      interleukin 13 (IL-13), IL-4 plays an important role in exacerbating allergic and
      asthmatic symptoms. For signal transduction, both cytokines can utilise the same
      receptor, consisting of the IL-4Ralpha and the IL-13Ralpha1 chain, offering an
      explanation for their overlapping biological functions. Since both cytokine
      ligands share only moderate similarity on the amino acid sequence level,
      molecular recognition of the ligands by both receptor subunits is of great
      interest. IL-4 and IL-13 are interesting targets for allergy and asthma
      therapies. Knowledge of the binding mechanism will be important for the
      generation of either IL-4 or IL-13 specific drugs. RESULTS: We present a
      structure/function analysis of the IL-4 ligand-receptor interaction. Structural
      determination of a number of IL-4 variants together with in vitro binding studies
      show that IL-4 and its high-affinity receptor subunit IL-4Ralpha interact via a
      modular protein-protein interface consisting of three independently-acting
      interaction clusters. For high-affinity binding of wild-type IL-4 to its receptor
      IL-4Ralpha, only two of these clusters (i.e. cluster 1 centered around Glu9 and
      cluster 2 around Arg88) contribute significantly to the free binding energy.
      Mutating residues Thr13 or Phe82 located in cluster 3 to aspartate results in
      super-agonistic IL-4 variants. All three clusters are fully engaged in these
      variants, generating a three-fold higher binding affinity for IL-4Ralpha.
      Mutagenesis studies reveal that IL-13 utilizes the same main binding
      determinants, i.e. Glu11 (cluster 1) and Arg64 (cluster 2), suggesting that IL-13
      also uses this modular protein interface architecture. CONCLUSION: The modular
      architecture of the IL-4-IL-4Ralpha interface suggests a possible mechanism by
      which proteins might be able to generate binding affinity and specificity
      independently. So far, affinity and specificity are often considered to co-vary,
      i.e. high specificity requires high affinity and vice versa. Although the binding
      affinities of IL-4 and IL-13 to IL-4Ralpha differ by a factor of more than 1000,
      the specificity remains high because the receptor subunit IL-4Ralpha binds
      exclusively to IL-4 and IL-13. An interface formed by several interaction
      clusters/binding hot-spots allows for a broad range of affinities by selecting
      how many of these interaction clusters will contribute to the overall binding
      free energy. Understanding how proteins generate affinity and specificity is
      essential as more and more growth factor receptor families show promiscuous
      binding to their respective ligands. This limited specificity is, however, not
      accompanied by low binding affinities.

PMID- 16640779
TI  - Evaluation of nutritional status in children with refractory epilepsy.
AB  - BACKGROUND: children affected by refractory epilepsy could be at risk of
      malnutrition because of feeding difficulties (anorexia, chewing, swallowing
      difficulties or vomiting) and chronic use of anticonvulsants, which may affect
      food intake and energy metabolism. Moreover, their energy requirement may be
      changed as their disabilities would impede normal daily activities. The aim of
      the present study was to evaluate nutritional status, energy metabolism and food
      intake in children with refractory epilepsy. METHODS: 17 children with refractory
      epilepsy (13 boys and 4 girls; mean age 9 +/- 3,2 years; Body Mass Index 15,7 +/-
      3,6) underwent an anthropometric assessment, body composition evaluation by dual
      energy X-ray absorptiometry, detailed dietetic survey and measurement of resting
      energy expenditure by indirect calorimetry. Weight-for-age, height-for-age
      (stunting) and weight-for-height (wasting) were estimated compared to those of a
      reference population of the same age. RESULTS: 40% of children were malnourished
      and 24% were wasted. The nutritional status was worse in the more disabled
      children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy
      intake derived respectively from protein, lipid and carbohydrate). Adequacy index
      [nutrient daily intake/recommended allowance (RDA) x 100] was < 60% for calcium
      iron and zinc. CONCLUSION: many children with refractory epilepsy would benefit
      from individual nutritional assessment and management as part of their overall
      care.

PMID- 16640780
TI  - A qualitative study in rural and urban areas on whether--and how--to consult
      during routine and out of hours.
AB  - BACKGROUND: Patients vary widely when making decisions to consult primary care.
      Some present frequently with trivial illness: others delay with serious disease.
      Differences in health service provision may play a part in this. We aimed to
      explore whether and how patients' consulting intentions take account of their
      perceptions of health service provision. METHODS: Four focus groups and 51 semi
      structured interviews with 78 participants (45 to 64 years) in eight urban and
      rural general practices in Northeast and Southwest Scotland. We used vignettes to
      stimulate discussion about what to do and why. Inductive analysis identified
      themes and explored the influence of their perceptions of health service
      provision on decision-making processes. RESULTS: Anticipated waiting times for
      appointments affected consulting intentions, especially when the severity of
      symptoms was uncertain. Strategies were used to deal with this, however: in
      cities, these included booking early just in case, being assertive, demanding
      visits, or calling out-of-hours; in rural areas, participants used relationships
      with primary care staff, and believed that being perceived as undemanding was
      advantageous. Out-of-hours, decisions to consult were influenced by opinions
      regarding out-of-hours services. Some preferred to attend nearby emergency
      departments or call 999. In rural areas, participants tended to delay until their
      own doctor was available, or might contact them even when not on call.
      CONCLUSION: Perceived barriers to health service access affect decisions to
      consult, but some patients develop strategies to get round them. Current changes
      in UK primary care are unlikely to reduce differences in consulting behaviour and
      may increase delays by some patients, especially in rural areas.

PMID- 16640781
TI  - In vitro comparison of antiviral drugs against feline herpesvirus 1.
AB  - BACKGROUND: Feline herpesvirus 1 (FHV-1) is a common cause of respiratory and
      ocular disease in cats. Especially in young kittens that have not yet reached the
      age of vaccination, but already lost maternal immunity, severe disease may occur.
      Therefore, there is a need for an effective antiviral treatment. In the present
      study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir,
      cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl)-2, 6
      diaminopurine (PMEDAP), against FHV-1 was compared in Crandell-Rees feline kidney
      (CRFK) cells using reduction in plaque number and plaque size as parameters.
      RESULTS: The capacity to reduce the number of plaques was most pronounced for
      ganciclovir, PMEDAP and cidofovir. IC50 (NUMBER) values were 3.2 microg/ml (12.5
      microM), 4.8 microg/ml (14.3 microM) and 6 microg/ml (21.5 microM), respectively.
      Adefovir and foscarnet were intermediately efficient with an IC50 (NUMBER) of 20
      microg/ml (73.2 microM) and 27 microg/ml (140.6 microM), respectively. Acyclovir
      was least efficient (IC50 (NUMBER) of 56 microg/ml or 248.7 microM). All
      antiviral drugs were able to significantly reduce plaque size when compared with
      the untreated control. As observed for the reduction in plaque number,
      ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC50
      (SIZE) values were 0.4 microg/ml (1.7 microM), 0.9 microg/ml (2.7 microM) and 0.2
      microg/ml (0.7 microM), respectively. Adefovir and foscarnet were intermediately
      potent, with an IC50 (SIZE) of 4 microg/ml (14.6 microM) and 7 microg/ml (36.4
      microM), respectively. Acyclovir was least potent (IC50 (SIZE) of 15 microg/ml or
      66.6 microM). The results demonstrate that the IC50 (SIZE) values were notably
      lower than the IC50 (NUMBER) values. The most remarkable effect was observed for
      cidofovir and ganciclovir. None of the products were toxic for CRFK cells at
      antiviral concentrations. CONCLUSION: In conclusion, measuring reduction in
      plaque number and plaque size are two valuable and complementary means of
      assessing the efficacy of an antiviral drug. By using these parameters for six
      selected antiviral drugs, we found that ganciclovir, PMEDAP, and cidofovir are
      the most potent inhibitors of FHV-1 replication in CRFK cells. Therefore, they
      may be valuable candidates for the treatment of FHV-1 infection in cats.

PMID- 16640782
TI  - Concomitant compostite adrenal phoechromocytoma, multipte gastric stromal tumours
      and pseudohermaphrodism in a patient with von Recklinghausen's disease.
AB  - Although pheochromocytoma occurs in 1% of patients with von Recklinghausen's
      disease, composite tumors in this syndrome are much rarer, with isolated case
      reports in the literature. Most gastrointestinal stromal tumors (GISTs) are
      solitary and sporadic. Multiple GISTs however, are associated with clinical
      syndromes particularly von Recklinghausen's disease. We believe this is the first
      report of composite adrenal pheochromocytoma and multiple GISTs occurring in an
      82 year old woman with neurofibromatosis type 1 (NF1), manifested by clitoral and
      subcutaneous neurofibromas, epilepsy and Lisch nodules. The extreme clitoromegaly
      raised concerns of pseudohermaphrodism at presentation.

PMID- 16640783
TI  - The effects of organic nitrates on osteoporosis: a randomized controlled trial
      [ISRCTN94484747].
AB  - BACKGROUND: Osteoporotic fractures are common and are associated with increased
      morbidity, mortality and health care costs. The most effective way to moderate
      increases in health care costs and the sickness and premature death associated
      with osteoporotic fractures, is to prevent osteoporosis. Several lines of
      evidence suggest that nitrates, drugs typically prescribed for the treatment of
      angina, may be effective in preventing postmenopausal osteoporosis. METHODS: We
      have designed a multicentre randomized controlled trial to determine the effects
      of nitrates on bone. The trial consists of two studies. The objective of the
      first study is to determine whether isosorbide mononitrate at 20 mg/day or
      nitroglycerin ointment at 15 mg/day leads to fewer headaches. The nitrate that is
      best tolerated will be used in a second study with one main objective: To
      determine if postmenopausal women with a T-score at the lumbar spine (L1 to L4)
      between 0 and -2.0 randomized to two years of treatment with intermittent
      nitrates have a greater increase in spine bone mineral density as compared to
      women randomized to placebo. We hypothesize that: 1. Women will report fewer
      headaches when they are randomized to intermittent nitroglycerin ointment at 15
      mg/day compared to intermittent oral isosorbide mononitrate at 20 mg/day, and, 2.
      After two years, women randomized to intermittent nitrates will have a greater
      percent increase in lumbar spine bone mineral density compared with women
      randomized to placebo. DISCUSSION: We have completed our pilot study and found
      that transdermal nitroglycerin was associated with fewer headaches than oral
      isosorbide mononitrate. We are currently recruiting patients for our second main
      study.

PMID- 16640784
TI  - Bioinformatic screening of human ESTs for differentially expressed genes in
      normal and tumor tissues.
AB  - BACKGROUND: Owing to the explosion of information generated by human genomics,
      analysis of publicly available databases can help identify potential candidate
      genes relevant to the cancerous phenotype. The aim of this study was to scan for
      such genes by whole-genome in silico subtraction using Expressed Sequence Tag
      (EST) data. METHODS: Genes differentially expressed in normal versus tumor
      tissues were identified using a computer-based differential display strategy. Bcl
      xL, an anti-apoptotic member of the Bcl-2 family, was selected for confirmation
      by western blot analysis. RESULTS: Our genome-wide expression analysis identified
      a set of genes whose differential expression may be attributed to the genetic
      alterations associated with tumor formation and malignant growth. We propose
      complete lists of genes that may serve as targets for projects seeking novel
      candidates for cancer diagnosis and therapy. Our validation result showed
      increased protein levels of Bcl-xL in two different liver cancer specimens
      compared to normal liver. Notably, our EST-based data mining procedure indicated
      that most of the changes in gene expression observed in cancer cells corresponded
      to gene inactivation patterns. Chromosomes and chromosomal regions most
      frequently associated with aberrant expression changes in cancer libraries were
      also determined. CONCLUSION: Through the description of several candidates
      (including genes encoding extracellular matrix and ribosomal components,
      cytoskeletal proteins, apoptotic regulators, and novel tissue-specific
      biomarkers), our study illustrates the utility of in silico transcriptomics to
      identify tumor cell signatures, tumor-related genes and chromosomal regions
      frequently associated with aberrant expression in cancer.

PMID- 16640785
TI  - Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer
      cells promoting apoptosis and G2/M cell cycle arrest.
AB  - BACKGROUND: New cancer therapeutic strategies must be investigated that enhance
      prostate cancer treatment while minimizing associated toxicities. We have
      previously shown that genistein, the major isoflavone found in soy, enhanced
      prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated
      the cellular and molecular interaction between genistein and radiation using PC-3
      human prostate cancer cells. METHODS: Tumor cell survival and progression was
      determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-kappaB,
      and western blot analysis of cyclin B1, p21WAF1/Cip1, and cleaved PARP protein.
      RESULTS: Genistein combined with radiation caused greater inhibition in PC-3
      colony formation compared to genistein or radiation alone. Treatment sequence of
      genistein followed by radiation and continuous exposure to genistein showed
      optimal effect. Cell cycle analysis demonstrated a significant dose- and time
      dependent G2/M arrest induced by genistein and radiation that correlated with
      increased p21WAF1/Cip1 and decreased cyclin B1 expression. NF-kappaB activity was
      significantly decreased by genistein, yet increased by radiation. Radiation
      induced activation of NF-kappaB activity was strongly inhibited by genistein pre
      treatment. A significant and striking increase in cleaved PARP protein was
      measured following combined genistein and radiation treatment, indicating
      increased apoptosis. CONCLUSION: A mechanism of increased cell death by genistein
      and radiation is proposed to occur via inhibition of NF-kappaB, leading to
      altered expression of regulatory cell cycle proteins such as cyclin B and/or
      p21WAF1/Cip1, thus promoting G2/M arrest and increased radiosensitivity. These
      findings support the important and novel strategy of combining genistein with
      radiation for the treatment of prostate cancer.

PMID- 16640786
TI  - Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse
      embryonic fibroblast cells.
AB  - BACKGROUND: We have demonstrated that in some human cancer cells both chronic
      mild heat and ionizing radiation exposures induce a transient block in S and G2
      phases of the cell cycle. During this delay, cyclin B1 protein accumulates to
      supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of
      the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC).
      RESULTS: Using syngenic mouse embryonic fibroblasts (MEF) with wild-type or
      mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase
      post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed
      by MC, while the wild-type p53 cells present both a lower accumulation of cyclin
      B1 and a lower frequency of MC. CONCLUSION: These results are in line with
      studies reporting the role of p53 as a post-transcriptional regulator of cyclin
      B1 protein and confirm that dysregulation of cyclin B1 promote radiation-induced
      MC. These findings might be exploited to design strategies to augment the yield
      of MC in tumor cells that are resistant to radiation-induced apoptosis.

PMID- 16640787
TI  - CREB activity maintains the survival of cingulate cortical pyramidal neurons in
      the adult mouse brain.
AB  - Cyclic AMP-responsive element binding protein (CREB) activity is known to
      contribute to important neuronal functions, such as synaptic plasticity, learning
      and memory. Using a microelectroporation technique to overexpress dominant
      negative mutant CREB (mCREB) in the adult mouse brain, we found that
      overexpression of mCREB in the forebrain cortex induced neuronal degeneration.
      Our findings suggest that constitutively active CREB phosphorylation is important
      for the survival of mammalian cells in the brain.

PMID- 16640788
TI  - IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give
      access to all TR potential V(D)J recombinations.
AB  - BACKGROUND: Adaptative immune repertoire diversity in vertebrate species is
      generated by recombination of variable (V), diversity (D) and joining (J) genes
      in the immunoglobulin (IG) loci of B lymphocytes and in the T cell receptor (TR)
      loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level
      involve recombination signal sequences (RSS). Whereas many data exist, they are
      scattered in non specialized resources with different nomenclatures (eg. flat
      files) and are difficult to extract. DESCRIPTION: IMGT/GeneInfo is an online
      information system that provides, through a user-friendly interface, exhaustive
      information resulting from the complex mechanisms of T cell receptor V-J and V-D
      J recombinations. T cells comprise two populations which express the alphabeta
      and gammadelta TR, respectively. The first version of the system dealt with the
      Homo sapiens and Mus musculus TRA and TRB loci whose gene rearrangements allow
      the synthesis of the alphabeta TR chains. In this paper, we present the second
      version of IMGT/GeneInfo where we complete the database for the Homo sapiens and
      Mus musculus TRG and TRD loci along with the introduction of a quality control
      procedure for existing and new data. We also include new functionalities to the
      four loci analysis, giving, to date, a very informative tool which allows to work
      on V(D)J genes of all TR loci in both human and mouse species. IMGT/GeneInfo
      provides more than 59,000 rearrangement combinations with a full gene description
      which is freely available at http://imgt.cines.fr/GeneInfo. CONCLUSION:
      IMGT/GeneInfo allows all TR information sequences to be in the same spot, and are
      now available within two computer-mouse clicks. This is useful for biologists and
      bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and
      their applications in immune response analysis.

PMID- 16640789
TI  - JColorGrid: software for the visualization of biological measurements.
AB  - BACKGROUND: Two-dimensional data colourings are an effective medium by which to
      represent three-dimensional data in two dimensions. Such "color-grid"
      representations have found increasing use in the biological sciences (e.g.
      microarray 'heat maps' and bioactivity data) as they are particularly suited to
      complex data sets and offer an alternative to the graphical representations
      included in traditional statistical software packages. The effectiveness of color
      grids lies in their graphical design, which introduces a standard for
      customizable data representation. Currently, software applications capable of
      generating limited color-grid representations can be found only in advanced
      statistical packages or custom programs (e.g. micro-array analysis tools), often
      associated with steep learning curves and requiring expert knowledge. RESULTS:
      Here we describe JColorGrid, a Java library and platform independent application
      that renders color-grid graphics from data. The software can be used as a Java
      library, as a command-line application, and as a color-grid parameter interface
      and graphical viewer application. Data, titles, and data labels are input as tab
      delimited text files or Microsoft Excel spreadsheets and the color-grid settings
      are specified through the graphical interface or a text configuration file.
      JColorGrid allows both user graphical data exploration as well as a means of
      automatically rendering color-grids from data as part of research pipelines.
      CONCLUSION: The program has been tested on Windows, Mac, and Linux operating
      systems, and the binary executables and source files are available for download
      at http://jcolorgrid.ucsf.edu.

PMID- 16640790
TI  - Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and
      normal aging patients.
AB  - BACKGROUND: It has been hypothesized that alterations of the serotonergic system
      contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular
      expressions of the two serotonergic receptors 5-HT2A and 5-HT6 have therefore
      been determined by immunohistochemistry in the prefrontal cortex of patients with
      AD (n=6) and normal age-matched controls (n = 7). RESULTS: In normal aging
      patients, 5-HT2A label was mainly observed in large pyramidal cells, but to a
      lesser extent also in small pyramidal cells and in stellate cells of cortical
      layers II-VI. In AD, a similar distribution was observed, but density of positive
      cells was significantly reduced by 33%. In aging control patients, the 5-HT6
      receptor was expressed by pyramidal cells and occasional stellate cells, not only
      of layers II-V, but also of layer I, where a distinct label was observed in
      neurons and surrounding fibers. 5-HT6 receptor expression in AD patients had the
      same pattern, but was significantly decreased by 40%. CONCLUSION: Our results
      indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6 receptors
      may play a role in the etiopathology of neuropsychiatric symptoms in AD.

PMID- 16640791
TI  - The genome of Rhizobium leguminosarum has recognizable core and accessory
      components.
AB  - BACKGROUND: Rhizobium leguminosarum is an alpha-proteobacterial N2-fixing
      symbiont of legumes that has been the subject of more than a thousand
      publications. Genes for the symbiotic interaction with plants are well studied,
      but the adaptations that allow survival and growth in the soil environment are
      poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae
      strain 3841. RESULTS: The 7.75 Mb genome comprises a circular chromosome and six
      circular plasmids, with 61% G+C overall. All three rRNA operons and 52 tRNA genes
      are on the chromosome; essential protein-encoding genes are largely chromosomal,
      but most functional classes occur on plasmids as well. Of the 7,263 protein
      encoding genes, 2,056 had orthologs in each of three related genomes
      (Agrobacterium tumefaciens, Sinorhizobium meliloti, and Mesorhizobium loti), and
      these genes were over-represented in the chromosome and had above average G+C.
      Most supported the rRNA-based phylogeny, confirming A. tumefaciens to be the
      closest among these relatives, but 347 genes were incompatible with this
      phylogeny; these were scattered throughout the genome but were over-represented
      on the plasmids. An unexpectedly large number of genes were shared by all three
      rhizobia but were missing from A. tumefaciens. CONCLUSION: Overall, the genome
      can be considered to have two main components: a 'core', which is higher in G+C,
      is mostly chromosomal, is shared with related organisms, and has a consistent
      phylogeny; and an 'accessory' component, which is sporadic in distribution, lower
      in G+C, and located on the plasmids and chromosomal islands. The accessory genome
      has a different nucleotide composition from the core despite a long history of
      coexistence.

PMID- 16640792
TI  - Mutation patterns of amino acid tandem repeats in the human proteome.
AB  - BACKGROUND: Amino acid tandem repeats are found in nearly one-fifth of human
      proteins. Abnormal expansion of these regions is associated with several human
      disorders. To gain further insight into the mutational mechanisms that operate in
      this type of sequence, we have analyzed a large number of mutation variants
      derived from human expressed sequence tags (ESTs). RESULTS: We identified 137
      polymorphic variants in 115 different amino acid tandem repeats. Of these, 77
      contained amino acid substitutions and 60 contained gaps (expansions or
      contractions of the repeat unit). The analysis showed that at least about 21% of
      the repeats might be polymorphic in humans. We compared the mutations found in
      different types of amino acid repeats and in adjacent regions. Overall, repeats
      showed a five-fold increase in the number of gap mutations compared to adjacent
      regions, reflecting the action of slippage within the repetitive structures. Gap
      and substitution mutations were very differently distributed between different
      amino acid repeat types. Among repeats containing gap variants we identified
      several disease and candidate disease genes. CONCLUSION: This is the first report
      at a genome-wide scale of the types of mutations occurring in the amino acid
      repeat component of the human proteome. We show that the mutational dynamics of
      different amino acid repeat types are very diverse. We provide a list of loci
      with highly variable repeat structures, some of which may be potentially involved
      in disease.

PMID- 16640793
TI  - A short screen for depression: the AB Clinician Depression Screen (ABCDS).
AB  - BACKGROUND: Depression is common in elderly people but physicians may not screen
      for it because of the length of time required by current screening instruments.
      We have developed a short screening instrument for depression for use in elderly
      people with normal cognition, mild cognitive impairment or early dementia.
      METHODS: Participants were aged 55 years or more, had scored 20 or more on the
      standardized Mini-mental State Examination (SMMSE) and had been referred to a
      specialist geriatric outpatient memory clinic. Scores on the 30-item Geriatric
      Depression Scale (GDS) were analyzed. A composite GDS score, consisting of the
      top five individual question scores that correlated to depression (GDS >or= 14),
      were analyzed using a receiver operating curve analysis. RESULTS: There were 810
      patients with SMMSE scores of 20 or greater, of whom 202 (24.9%) scored 14 or
      more on the GDS, indicating depression. GDS question 16, "Do you often feel
      downhearted and blue?," had the highest correlation with the overall scores of 14
      or more on the 30-point instrument (r = 0.64, p < 0.001). The next four questions
      with the highest correlates were Q10, "Do you often feel helpless?" (r = 0.56, p
      < 0.001), Q3, "Do you feel that your life is empty?" (r = 0.54, p < 0.001), Q9,
      "Do you feel happy most of the time?" (r = 0.52, p < 0.001), and Q1, "Are you
      basically satisfied with your life?" (r = 0.50, p < 0.001). The negative
      predictive value of "Do you often feel downhearted and blue?" answered negatively
      for depression was 96%. These five questions were used as a short screening
      instrument. The positive predictive value of four or five positive responses was
      97%. These data were not significantly different whether the patient's SMMSE
      score was 20-25 or 26-30. CONCLUSIONS: The AB Clinician Depression Screen
      (ABCDS), comprising five questions, can rapidly identify patients with depression
      or eliminate that diagnosis. In this population, these five questions may be used
      instead of the longer 30-question GDS scale.

PMID- 16640794
TI  - The development of a semi-structured home interview (CHIF) to directly assess
      function in cognitively impaired elderly people in two cultures.
AB  - BACKGROUND: Assessing function is a crucial element in the diagnosis of dementia.
      This information is usually obtained from key informants. However, reliable
      informants are not always available. METHODS: A 10-item semi-structured home
      interview (the CHIF, or Clinician Home-based Interview to assess Function) to
      assess function primarily by measuring instrumental activities of daily living
      directly was developed and tested for inter-rater reliability and validity as
      part of the Indianapolis-Ibadan dementia project. The primary validity
      measurements were correlations between scores on the CHIF and independently
      gathered scores on the Blessed Dementia Scale (from informants) and the Mini
      mental State Examination (MMSE). Sensitivities and specificities of scores on the
      CHIF and receiver operator characteristic (ROC) curves were constructed with
      dementia as the dependent variable. RESULTS: Inter-rater reliability for the CHIF
      was high (Pearson's correlation coefficient 0.99 in Indianapolis and 0.87 in
      Ibadan). Internal consistency, in both samples, was good (Cronbach's alpha 0.95
      in Indianapolis and 0.83 in Ibadan). Scores on the CHIF correlated well with the
      Blessed Dementia scores at both sites (-0.71, p < 0.0001 for Indianapolis and 
      0.56, p < 0.0001 for Ibadan) and with the MMSE (0.75, p < 0.0001 for Indianapolis
      and 0.44, p < 0.0001 for Ibadan). For all items at both sites, the subjects
      without dementia performed significantly better than those with dementia. The
      area under the ROC curve for dementia diagnosis was 0.965 for Indianapolis and
      0.925 for Ibadan. CONCLUSION: The CHIF is a useful instrument to assess function
      directly in elderly participants in international studies, particularly in the
      absence of reliable informants.

PMID- 16640796
TI  - Animal-assisted therapy for dementia: a review of the literature.
AB  - BACKGROUND: Animal-assisted therapy (AAT) is gaining popularity as part of
      therapy programs in residential aged care facilities. Humans and pet dogs respond
      to quiet interaction with a lowering of blood pressure and an increase in
      neurochemicals associated with relaxation and bonding. These effects may be of
      benefit in ameliorating behavioral and psychological symptoms of dementia (BPSD).
      METHODS: Medline, PsychInfo and CINAHL databases (1960-2005) were searched for
      papers on AAT or pets and dementia. Publications of controlled trials that
      measured the effect of AAT for dementia were reviewed. RESULTS: Several small
      studies suggest that the presence of a dog reduces aggression and agitation, as
      well as promoting social behavior in people with dementia. One study has shown
      that aquaria in dining rooms of dementia care units stimulate residents to eat
      more of their meals and to gain weight but is limited by the small number of
      facilities studied. There is preliminary evidence that robotic pets may provide
      pleasure and interest to people with dementia. CONCLUSIONS: Current literature
      suggests that AAT may ameliorate BPSD, but the duration of the beneficial effect
      has not been explored. The relative benefits of "resident" versus "visiting" pet
      dogs are unclear and are confounded by the positive effect of pet interaction on
      staff or caregivers. Further research on the potential benefits of AAT is
      recommended.

PMID- 16640797
TI  - An 18-month prospective cohort study of functional outcome of delirium in elderly
      patients: activities of daily living.
AB  - OBJECTIVES: To examine delirium, chronic medical problems and sociodemographic
      factors as predictors of activities of daily living (ADL), basic ADL (BADL) and
      instrumental ADL (IADL). METHODS: A prospective cohort study of four groups of
      elderly patients examined in the emergency department (ED): those with delirium,
      dementia, neither, and both. All were aged 66 years or older and living at home.
      Delirium was assessed with the Confusion Assessment Method and dementia with the
      Informant Questionnaire on Cognitive Decline in the Elderly. Demographic
      variables and chronic medical problems were ascertained with questionnaires.
      Outcome was ADL at 6, 12 and 18 months, measured with the ADL subscale of the
      Older Americans Resources and Services instrument. RESULTS: Univariate analyses
      suggested significantly poorer ADL, particularly IADL, at 18 months in the
      delirium versus the non-delirium group, in the absence of dementia only.
      Statistically significant independent predictors of poorer ADL at 18 months in
      the non-dementia groups were poorer initial ADL, stroke, Parkinson's disease,
      hypertension and female sex. Independent predictors of poorer BADL at 18 months
      in the non-dementia groups were poorer initial BADL, Parkinson's disease, stroke,
      cancer, colds/sinusitis/laryngitis, female sex and hypertension. Independent
      predictors of poorer IADL at 18 months in the non-dementia groups were poorer
      initial IADL, stroke, never-married status, colds/sinusitis/laryngitis, arthritis
      and hypertension, with Parkinson's disease showing a non-significant but
      numerically large regression coefficient. CONCLUSION: Rather than finding
      delirium to be a predictor of poorer functional outcome among survivors, we found
      an interaction between delirium and dementia and several plausible confounders,
      primarily chronic medical problems, although we cannot rule out the effect of
      misclassification or survivor bias.

PMID- 16640798
TI  - Classification of patterns of delirium severity scores over time in an elderly
      population.
AB  - OBJECTIVES: To describe and classify individual trajectories of 15-day changes in
      delirium severity. METHODS: A longitudinal hospital-based study was carried out
      with 230 medical inpatients aged 65 and over admitted to St Mary's Hospital in
      Montreal, Canada, between 1996 and 1999, diagnosed with delirium at enrollment,
      and who had at least four measurements of delirium severity during the next 15
      days. Delirium severity was assessed using the Delirium Index (DI). To classify
      patients' individual trajectories, we applied a new method that relies on
      principal factor analysis and cluster analysis. We used multiple linear
      regression to investigate if clusters were associated with DI scores measured at
      an 8-week follow-up. Multivariable Cox's proportional hazards regression was used
      to assess whether the clusters were associated with survival over the next 12
      months. RESULTS: Individual patterns were classified into five clusters: Steady
      (n = 89, 38.9%), Fluctuating (n = 36, 15.7%), Worsening (n = 15, 6.6%), Fast
      Improve-ment (n = 26, 11.3%), and Slow Improvement (n = 63, 27.5%). The Fast
      Improvement cluster had much lower prevalence of dementia (38.5% vs. 55.6% to
      77.8% in other clusters, p = 0.003). Subjects whose 2-week patterns were
      classified as Fast or Slow Improvement had a significantly lower DI at 8 weeks
      than those in the Steady or Fluctuating clusters. The Worsening cluster had the
      largest percentage of deaths. The Fast Improvement and Worsening clusters
      initially had a high risk of death in the first 2 weeks (adjusted relative risks
      of approximately 3 and 6, respectively) but that risk decreased rapidly
      thereafter. CONCLUSION: Two-week trajectories of delirium severity were
      associated with short-term mortality and delirium severity at 8-week follow-up.

PMID- 16640799
TI  - Bronchioloalveolar carcinoma: the "changing face of lung cancer".

PMID- 16640800
TI  - Emerging antiangiogenic agents in lung cancer.
AB  - The success of the anti-vascular endothelial growth factor (VEGF) antibody
      bevacizumab in numerous tumor types including non-small-cell lung cancer (NSCLC)
      has spurred the development of additional novel antiangiogenic agents with
      distinct mechanisms of action. These include the small-molecule receptor tyrosine
      kinase (TK) inhibitors ZD6474, sorafenib, sunitinib malate, and AG-013736, all of
      which inhibit VEGF receptor TK activity. Because of the structural similarity of
      the different receptor TKs, these receptor TK inhibitors inhibit multiple
      receptors in addition to VEGF receptor. Vascular endothelial growth factor Trap,
      a novel, high-affinity molecule with specificity to the VEGF molecule, was
      generated as a fusion molecule of the VEGF receptor extracellular domain and the
      Fc portion of immunoglobulin (Ig) G1. Data from phase I/II trials have indicated
      the clinical feasibility of these agents, which are currently being investigated
      in phase II/III trials.

PMID- 16640801
TI  - The potential of histone deacetylase inhibitors in lung cancer.
AB  - In the nucleus, DNA is wrapped around octamers of histone proteins. Histones,
      like other proteins, are posttranslationally modified by the addition of an array
      of chemical groups that affect their interactions with surrounding structures.
      Histone acetyltransferases and histone deacetylases (HDACs) are the enzymes
      involved in the addition and removal, respectively, of acetyl groups from the
      aminoterminal tails of histones. A number of structurally diverse compounds are
      capable of inhibiting HDACs and exert a variety of biologic effects on cancer
      cells in preclinical models. Early clinical trials with the first generation of
      HDAC inhibitors (HDACIs) have demonstrated promising therapeutic activity, and
      HDACs have become one of the hottest targets in drug development today.

PMID- 16640802
TI  - Bronchioloalveolar carcinoma: a review.
AB  - Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung
      adenocarcinoma but has a distinct clinical presentation, tumor biology, response
      to therapy, and prognosis compared with other subtypes of non-small-cell lung
      carcinoma (NSCLC). Bronchioloalveolar carcinoma disproportionately affects women,
      never-smokers, and Asians and is characterized by growth along alveolar septae
      without evidence of stromal, vascular, or pleural invasion. Although pure BAC
      accounts for approximately 4% of lung cancers, tumors with histologically mixed
      BAC and adenocarcinoma account for > 20% of all NSCLCs, and the incidence of BAC
      might be increasing. Bronchioloalveolar carcinoma histology is most commonly
      found in small lesions identified incidentally on chest radiographs or computed
      tomography scans and might represent a precursor lesion to invasive
      adenocarcinoma. As with other subsets of NSCLC, surgical resection is the only
      potentially curative treatment. Patients with unresectable BAC are more likely to
      respond to the epidermal growth factor receptor tyrosine kinase inhibitors
      gefitinib and erlotinib than patients with other subtypes of NSCLC. Stage for
      stage, patients with BAC have a higher rate of long-term survival but might have
      an increased rate of intrathoracic recurrence than patients with other subtypes
      of NSCLC.

PMID- 16640803
TI  - Computed tomography screening for lung cancer: prospects of surviving competing
      causes of death.
AB  - PURPOSE: The primary objective of this study was to shed light on the frequency
      of death from a "competing" cause among persons who enter into computed
      tomography (CT) screening for lung cancer and to determine the 5- and 10-year
      rates of death from causes other than lung cancer in a cohort of older smokers
      and former smokers with the initiation of CT screening for lung cancer. PATIENTS
      AND METHODS: We followed a cohort of 2141 men and women aged 60-75 years with a
      history of 30-100 pack-years of cigarette smoking who enrolled for CT screening
      for lung cancer in 1993-2004. The National Death Index retrieval program was used
      to identify all deaths and causes of death. Follow-up time from the date of the
      initial CT to death, loss to follow-up, or December 31, 2004, whichever came
      first, was calculated for each subject. Median duration of follow-up was 50
      months (range, 1-133 months). Kaplan-Meier analysis was used to derive the 5- and
      10-year survival rates with the exclusion of deaths from lung cancer. RESULTS:
      The 5- and 10-year survival rates, conditional on not dying from lung cancer,
      were 96% and 90.7%, respectively. The corresponding 95% confidence intervals were
      95%-97% and 88.2%-95.2%, respectively. CONCLUSION: Older smokers and former
      smokers seeking and receiving CT screening for lung cancer have a low 10-year
      risk of dying from causes other than lung cancer, and early treatment of screen
      diagnosed cancer can be life-saving.

PMID- 16640804
TI  - Asian ethnicity as a predictor of response in patients with non-small-cell lung
      cancer treated with gefitinib on an expanded access program.
AB  - BACKGROUND: The primary objective of this retrospective study was to investigate
      the potential role of East Asian ethnicity or origin in predicting response to
      gefitinib in advanced-stage non-small-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: A chart review was done of all patients treated with gefitinib at M. D.
      Anderson Cancer Center on the Expanded Access Program. RESULTS: There were 223
      patients with advanced-stage NSCLC who were enrolled. Of these, 182 received >or=
      1 dose, and 160 were evaluable for response. The partial response rate was 8.8%,
      and the stable disease rate was 26.3%. Median time to progression was 2.5 months,
      and median survival was 6.8 months. The 1- and 2-year survival rates were 35.3%
      and 12.4%, respectively. Partial responses were seen in 7 of 12 patients (58.3%)
      of East Asian origin compared with 7 of 131 patients who were white (5.3%). This
      difference was statistically significant when controlling for histology, smoking
      status, hemoglobin, and diarrhea. Never smoking and diarrhea were also
      independent predictors of response. CONCLUSION: For the first time, in a
      multivariate analysis, we observed a positive relationship between East Asian
      origin and response to gefitinib. These findings might help determine which
      patients will likely benefit from gefitinib.

PMID- 16640805
TI  - Sex differences in the predictive power of the molecular prognostic factor
      HER2/neu in patients with non-small-cell lung cancer.
AB  - BACKGROUND: Recent studies imply that HER2/neu is a potential prognostic factor
      in patients with non-small-cell lung cancer (NSCLC). Whereas considerable
      evidence indicates sex differences in epidemiologic, hormonal, biologic, and
      genetic factors in this disease, it has remained unknown whether HER2/neu has a
      diverse function as a prognostic factor in men and women. PATIENTS AND METHODS:
      We investigated the association between gene expression levels of HER2/neu in the
      primary tumors of 90 patients with curable resected NSCLC and survival,
      especially analyzing whether there is a different potential of this molecular
      factor in its prognostic impact between men and women. RESULTS: High HER2/neu
      gene expression levels were found in 62 patients (68.9%), and low HER2/neu gene
      expression levels were found in 28 patients (31.1%). High HER2/neu messenger RNA
      expression levels were associated with inferior survival (P = 0.09) compared with
      lower HER2/neu expression. Survival analysis was then carried out separately for
      men and women in this group of patients. An HER2/neu gene expression cutoff point
      was identified that separated women, but not men, into good and poor prognostic
      groups. CONCLUSION: These findings suggest that HER2/neu as a prognostic factor
      is strongly sex specific, indicating that it is not useful for men but highly
      predictive for women.

PMID- 16640806
TI  - Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using
      every-3-week versus weekly paclitaxel/carboplatin.
AB  - PURPOSE: The combination of paclitaxel with carboplatin is effective in advanced
      stage non-small cell lung cancer (NSCLC). This phase III study was designed to
      compare the efficacy and tolerability of a weekly versus an every-3-week schedule
      in the first-line treatment of advanced-stage NSCLC. PATIENTS AND METHODS:
      Chemotherapy-naive patients were randomized to receive paclitaxel 100 mg/m2 and
      carboplatin at an area under the curve of 2 once weekly for 6-8 weeks (arm A) or
      paclitaxel 200 mg/m2 and carboplatin at an area under the curve of 6 on day 1
      every 21 days (arm B). RESULTS: A total of 883 patients received >or= 1
      chemotherapy cycle and were included in the results. The objective response rates
      observed (complete response plus partial response) were 38% for arm A and 33% for
      arm B. Median times to progression and median survival times were 6.1 months and
      8.9 months in arm A and 7.2 months and 9.5 months in arm B, respectively. There
      were no significant differences between treatment arms. The chemotherapy was well
      tolerated in both schedules. However, grade 3/4 sensory neuropathy occurred more
      frequently with the every-3-week schedule (9.1% vs. 4.4%), whereas grade 3/4
      diarrhea occurred more frequently with the weekly schedule (4.2% vs. 1.1%).
      CONCLUSION: In terms of response and survival, paclitaxel/carboplatin
      administered once weekly is comparable with the every-3-week schedule. Toxicity
      differences should be considered when choosing the appropriate schedule for the
      individual.

PMID- 16640807
TI  - Pulmonary dysfunction as a major cause of inoperability among patients with non
      small-cell lung cancer.
AB  - PURPOSE: We wanted to assess the prevalence of pulmonary dysfunction as the
      underlying reason for inoperability among patients with non-small-cell lung
      cancer (NSCLC) who were considered for surgical treatment at the time of
      diagnosis. PATIENTS AND METHODS: This is a retrospective analysis of all patients
      with NSCLC referred to our pulmonary function laboratory for preoperative
      evaluation between January 2001 and November 2001. Pulmonary function testing
      consisted of measurement of spirometric indices (forced expiratory volume in 1
      second [FEV1]), lung volumes and diffusing capacity for carbon monoxide, Xenon
      133 quantitative ventilation and perfusion studies, and exercise testing when
      indicated. Patient demographics and clinical characteristics at the time of the
      evaluation were reviewed. RESULTS: The group comprised 206 consecutive potential
      surgical candidates (mean age, 64.7 years +/- 10.1 years) with NSCLC. Nearly half
      (45.6%) of the patients had early-stage (I/II) disease, and the remainder had
      late-stage disease at the time of pulmonary evaluation. The average predicted
      FEV1 among all patients was 70.3% +/- 19.6% (range, 25%-123%). One hundred eight
      patients (52.4%) were deemed surgically inoperable after the preoperative
      assessment. Severe pulmonary function impairment was identified as the reason for
      surgical inoperability in more than one third of these patients (40 of 108).
      CONCLUSION: A substantial number of patients with anatomically resectable NSCLC
      are deemed surgically ineligible based on poor lung function. Recognition of the
      magnitude of this problem is fundamental to the development of effective
      treatment options, which might include preoperative management strategies that
      could better prepare patients for surgery or, alternatively, aggressive
      nonsurgical approaches.

PMID- 16640808
TI  - Right partial anomalous pulmonary venous connection found during lobectomy for
      coexisting lung cancer and tuberculosis: report of a case.
AB  - Herein, we report a rare case of a 59-year-old man in whom a partial anomalous
      pulmonary venous connection was found during an operation for coexisting lung
      cancer and tuberculosis. It was observed that the anomalous vein drained only
      from the right upper lobe into the right superior vena cava. The middle and lower
      pulmonary veins connected normally, and there was no atrial septal defect or any
      other anomalous condition. An upper lobectomy for coexisting lung cancer and
      tuberculosis with ligation of the partial anomalous pulmonary venous connection
      was successfully performed.

PMID- 16640809
TI  - Randomized phase III trial of cisplatin/irinotecan versus cisplatin/etoposide in
      patients with extensive-stage small-cell lung cancer.

PMID- 16640810
TI  - 47th Annual Meeting of the American Society of Hematology Atlanta, GA.

PMID- 16640812
TI  - The role of high-dose therapy in peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non
      Hodgkin's lymphomas. With few exceptions (eg, anaplastic large-cell lymphoma
      expressing the anaplastic lymphoma kinase), PTCLs have generally been reported to
      have a worse prognosis compared with B-cell lymphomas. Despite the poor outcome
      after conventional therapy, the impact of high-dose therapy with autologous or
      allogeneic stem cell transplantation (SCT) in these rare diseases is poorly
      defined mainly because of the lack of prospective PTCL-restricted studies. Most
      data exist for high-dose therapy with autologous SCT in relapsing or refractory
      disease. Because most studies showed similar results for PTCL compared with
      aggressive B-cell lymphomas in which high-dose therapy with autologous SCT is
      accepted as standard therapy, this approach seems appropriate in relapsing or
      refractory PTCL. Results for high-dose therapy with autologous SCT as first-line
      therapy mainly rely on studies on aggressive lymphomas that also included
      lymphomas of the T-cell phenotype. Our own recently published PTCL-restricted
      prospective study confirmed the feasibility with only moderate toxicity and a
      good response rate. Overall, patients with a good remission status after
      induction therapy exhibited a high complete response rate after transplantation,
      and at least a subgroup of patients remained in long-term remission. The greatest
      uncertainty exists for the impact of allogeneic SCT after high-dose therapy. In
      refractory or relapsing PTCL, this approach might improve the outcome for
      eligible patients, especially when using reduced-intensity conditioning. Overall,
      because data on high-dose therapy for PTCL are limited, larger and randomized
      studies are necessary to definitely confirm the preliminary results.

PMID- 16640813
TI  - Update on recommendations for assessing response from the Third International
      Workshop on Waldenstrom's Macroglobulinemia.
AB  - This report by an international consensus panel updates current recommendations
      for defining clinical response in Waldenstrom's macroglobulinemia (WM). The
      previously published response criteria incorporated parameters for monoclonal
      protein reduction and/or improvement of marrow and nodal involvement, and
      included definitions of complete and partial remissions. The criteria have been
      updated to include minor response and stable disease categories. In addition, the
      criteria now recognize that delayed responses after treatment with nucleoside
      analogues and biologic agents and the time point for assessing response in
      patients with WM should be considered so as to not miss or miscategorize a
      response. The new criteria should therefore help in better delineating responses
      to therapy in patients with WM, particularly with the wide use of nucleoside
      analogues and biologically based agents for this disease.

PMID- 16640814
TI  - Cyclophosphamide mobilization does not improve outcome in patients receiving stem
      cell transplantation for multiple myeloma.
AB  - PURPOSE: Patients with multiple myeloma who undergo autologous stem cell
      transplantation (ASCT) and exhibit a complete response (CR) have a superior
      overall survival and time to progression (TTP). High-dose cyclophosphamide is
      often used before ASCT for mobilization of hematopoietic stem cells. We
      hypothesized that cyclophosphamide might further improve CR rates in patients
      undergoing ASCT. We searched the Mayo Clinic myeloma transplantation database for
      patients who had stem cell mobilization with hematopoietic growth factor alone or
      cyclophosphamide and growth factor. The impact of cyclophosphamide on CR rates
      and TTP was evaluated. PATIENTS AND METHODS: A cohort of 201 patients was
      identified: 127 mobilized with cyclophosphamide and growth factor and 74 with
      growth factor alone. There were no statistically significant differences between
      the 2 cohorts in regard to age, sex, b2-microglobulin level, plasma cell labeling
      index, cytogenetics, conditioning regimen, or disease status at time of
      transplantation. RESULTS: Complete response rates were 37.4% and 41.3% (P =
      0.6115) for patients mobilized with cyclophosphamide combined with growth factor
      and growth factor alone, respectively, and TTPs were 19.9 months and 20.9 months
      (P = 0.59). In a multivariate analysis for TTP, cytogenetics and CR rates were
      the only independent variables (P = 0.0012 and P < 0.0001, respectively).
      CONCLUSION: We conclude that high-dose cyclophosphamide does not increase overall
      CR rates or improve TTP for patients with myeloma undergoing ASCT.

PMID- 16640815
TI  - Treatment for relapse in stage I/II Hodgkin's lymphoma after initial single
      modality treatment.
AB  - BACKGROUND: Doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) chemotherapy
      alone is a viable option for the treatment of stage I/II Hodgkin's lymphoma.
      Among the main drawbacks for widespread acceptance of this therapy is the absence
      of available data on the post-salvage therapy course in patients with limited
      stage disease who relapse after ABVD. This article focuses on the outcome of 11
      limited-stage patients who relapsed after ABVD alone. PATIENTS AND METHODS: After
      a clinical restaging, the patients received mantle-type radiation therapy (only
      if patients met these criteria: supradiaphragmatic disease in a single-node area,
      erythrocyte sedimentation rate < 30 mm per hour, and absence of B symptoms) or
      conventional salvage chemotherapy followed by high-dose chemotherapy and
      autologous hematopoietic stem cell transplantation. RESULTS: After a median
      follow-up of 64 months, 10 patients showed complete response and are still alive
      without disease progression. One patient showed refractory disease and died 9
      months after relapse. This experiment entails the series with the longest follow
      up in patients with limited-stage Hodgkin's lymphoma who relapsed after ABVD
      alone. CONCLUSION: The data seem to indicate that salvage therapy is capable of
      providing cure in most cases and lend further support for the use of ABVD alone
      as first-line therapy.

PMID- 16640816
TI  - Cytomegalovirus infection in patients with lymphoma: an important cause of
      morbidity and mortality.
AB  - BACKGROUND: Cytomegalovirus (CMV) antigenemia (CMV-A) and CMV disease (CMV-D),
      known causes of morbidity and mortality among patients with leukemia and
      recipients of hematopoietic stem cell transplantations, are described
      sporadically in patients with lymphoma. We sought to determine the risk factors
      and outcome of CMV-A and CMV-D among patients with lymphoma. PATIENTS AND
      METHODS: We conducted a retrospective cohort study with such patients identified
      between 1997 and 2003 at The University of Texas M. D. Anderson Cancer Center.
      Seventy-one patients with 82 episodes of CMV-A and/or CMV-D (CMV-A in 38 episodes
      and CMV-D in 44 episodes) were studied. RESULTS: Cytomegalovirus antigenemia
      and/or CMV-D were more common among patients with non-Hodgkin's lymphoma than
      among those with Hodgkin's disease (P = 0.01). Most CMV infectious episodes
      occurred in patients who had active (88%) and stage III/IV lymphoma (84%). Eleven
      of 65 patients (17%) with outcome data died with CMV-A and/or CMV-D. Death with
      CMV infection was more common among patients with CMV-D than among those with CMV
      A (29% vs. 3%, respectively, P = 0.005). Predictors of death by univariate
      analysis included intensive care unit admission, mechanical ventilation, high
      antigenemia burden, relapse of CMV-A and/or CMV-D, and antiviral-associated
      toxicity (all P < 0.05). Multivariate analysis identified antiviral toxicity as
      the only independent predictor of death (P = 0.01). CONCLUSION: In an era of
      intense and pleiotropic immunosuppressive therapy in patients with lymphoma, CMV
      A and CMV-D are significant infections. Preventive strategies might be warranted
      for patients at risk.

PMID- 16640817
TI  - Antiviral and immunomodulatory treatment for AIDS-related primary central nervous
      system lymphoma: AIDS Malignancies Consortium pilot study 019.
AB  - PURPOSE: A consistent association with Epstein-Barr Virus (EBV) distinguishes
      acquired immunodeficiency syndrome (AIDS)-related primary central nervous system
      lymphoma (PCNSL) from that which occurs in the general population. Recent
      descriptions of long-term remissions in patients with posttransplantation EBV
      associated PCNSL who received EBV-specific therapy suggest some antitumor effect
      is anti-EBV mediated. PATIENTS AND METHODS: We enrolled 4 patients with AIDS
      related PCNSL into a novel antiviral and immunomodulatory protocol. An additional
      patient was treated in a similar fashion off protocol. Treatment consisted of
      intravenously administered zidovudine (1.5 g twice daily), ganciclovir (5 mg/kg
      twice daily), and interleukin-2 (2,000,000 U twice daily). After 2 weeks of
      therapy, patients were switched to oral ganciclovir (1 g 3 times daily), patient
      specific, highly active, antiretroviral therapy, and subcutaneous interleukin-2
      (2,000,000 U 3 times weekly). A final patient was treated with intravenous
      zidovudine and hydroxyurea. All 6 patients had advanced-stage AIDS as reflected
      by a CD4+ T-lymphocyte cell count of < 50/microL and a detectable human
      immunodeficiency virus (HIV)-1 viral RNA load (median copies, 135,000/mL; range,
      2170-360,000/mL). One of 4 protocol-enrolled patients remains in complete
      remission with > 4 years' follow-up. RESULTS: Three patients died from
      complications of progressive PCNSL. Two patients treated off protocol exhibited
      favorable responses and remain in complete remission at 28 months and 52 months,
      respectively. Grade 3/4 myelosuppression was uniformly noted, but there were no
      clinically significant hemorrhagic or infectious complications. CONCLUSION: We
      conclude that for patients with AIDS and PCNSL, treatments with dual efficacy
      against HIV and EBV merit further investigation. Our experience provides a
      platform for future studies.

PMID- 16640818
TI  - Non-Hodgkin's lymphoma of the renal pelvis.
AB  - Primary lymphoma of the upper urinary tract is an extremely rare entity without
      specific clinical or laboratory findings. Thus, this particular diagnosis is
      rarely anticipated and might well be reached only after nephroureterectomy. We
      describe a patient with primary follicular and diffuse follicle center lymphoma
      arising in the renal pelvis that was treated with surgery and postoperative
      immunochemotherapy. Furthermore, we review the literature regarding the treatment
      and outcome of this rare disease.

PMID- 16640819
TI  - Fatal interstitial pneumonitis related to rituximab-containing regimen.
AB  - Rituximab, a chimeric anti-CD20 monoclonal antibody, is commonly being used to
      treat indolent and aggressive B-cell non-Hodgkin's lymphoma. Rituximab is
      considered a relatively safe drug, but recently, severe and fatal adverse effects
      related to this drug have been reported. In this regard, we report an 80-year-old
      patient with follicular grade 3 non-Hodgkin's lymphoma who developed a fatal
      interstitial pneumonitis related to treatment with a rituximab/CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen. The pneumonitis
      was diagnosed on a routine midtreatment positron emission tomography/computed
      tomography scan when the patient was almost asymptomatic. Pulmonary deterioration
      occurred as the treatment with rituximab/CHOP was continued. In this article, we
      also review the literature on rituximab-associated pneumonitis, and we discuss
      the differential diagnosis with cyclophosphamide-induced lung injury.

PMID- 16640820
TI  - Classical Hodgkin's lymphoma presenting with tongue involvement: a case report
      and review of the literature.
AB  - We report an unusual case of mixed cellularity classical Hodgkin's lymphoma with
      prominent involvement of the base of the tongue at diagnosis. In situ
      hybridization findings for Epstein-Barr virus were positive. Waldeyer's ring
      involvement by Hodgkin's lymphoma is uncommon with < 200 cases reported in the
      English literature and only 5 previous reports of Hodgkin's lymphoma involving
      the tongue.

PMID- 16640821
TI  - A malignant fibroleiomyoma of the testis.
AB  - The patient described has a 2-cm, hard, painless nodule close to an atrophic
      testis that had been present for > 10 years, suggesting inactive disease,
      recently associated with fever of undetermined origin with constitutional
      symptoms. Extensive examinations of pleural, spinal, and bronchoalveolar fluids;
      bacterial and mycobacterial cultures; bone biopsies; and computed tomography
      scans were inconclusive. Orchiectomy demonstrated an angiotropic large B-cell
      lymphoma (CD19+CD20+CD79a+) in the context of a benign fibroleiomyoma. The
      symptoms abated after the first of 4 rituximab injections. Reports suggest that
      benign tumors can be harbingers of angiotropic lymphoma or facilitate its onset.
      To date, no testicular or epididymal primary site has been reported for
      angiotropic lymphoma.

PMID- 16640822
TI  - Fas ligand-mediated lethal hepatitis after rapid lysis of a localized natural
      killer cell lymphoma.
AB  - Natural killer (NK) cell malignancies have been associated with neutropenia and
      disturbances of liver function tests, thought to be related to high levels of
      soluble Fas ligand (FasL) in the circulation. We report a case of fulminant
      hepatitis occurring 3 weeks after the initiation of salvage therapy by arginine
      butyrate and ganciclovir for refractory Epstein-Barr virus-positive NK cell
      lymphoma. Pathologic examination revealed disappearance of the NK tumor and
      massive liver injury caused by apoptosis of virtually all hepatocytes.
      Immunohistochemistry revealed an intense staining for FasL. To our knowledge,
      this is the first description of the occurrence of FasL-mediated lethal hepatitis
      after lysis of a NK cell lymphoma.

PMID- 16640823
TI  - Surgical resection of primary cardiac lymphoma.
AB  - Primary cardiac lymphoma is a rare cardiac malignancy. Surgical resection is
      rarely performed on this disease entity. We report a case of primary cardiac
      lymphoma with rapid progression. Debulking surgery was done extensively before
      final pathology was obtained. Complete remission was exhibited after several
      courses of chemotherapy.

PMID- 16640824
TI  - Eastern Cooperative Oncology Group 4402: Rituximab Extended Schedule or
      Retreatment Trial (RESORT).

PMID- 16640825
TI  - Therapeutic potential of iron chelators in diseases associated with iron
      mismanagement.
AB  - A considerable array of diseases are now recognized to be associated with
      misplacement of iron. Excessive deposits of the metal in sensitive tissue sites
      can result in formation of destructive hydroxyl radicals as well as in
      stimulation of growth of neoplastic and microbial cell invaders. To counteract
      potential iron damage, hosts employ the iron chelators, transferrin and
      lactoferrin. These proteins have been recently developed into pharmaceutical
      products. Additionally, a variety of low molecular mass iron chelators are being
      used/tested to treat whole body iron loading, and specific diseases for which the
      metal is a known or suspected risk factor.

PMID- 16640826
TI  - Cytotoxic evaluation of injectable cyclodextrin nanoparticles.
AB  - Nanoparticles were prepared using beta-CDC6, which is an amphiphilic beta
      cyclodextrin derivative modified on the secondary face with 6C aliphatic esters.
      A nanoprecipitation technique was used to prepare the blank nanoparticles without
      any surfactant and nanoparticles containing Pluronic F68 as surfactant in a
      concentration range of 0.1 to 1%. Nanoparticle formulations were characterized by
      particle size distribution and zeta potential measurements. Entrapment efficiency
      and in-vitro release profiles were determined and the cytotoxicity of these
      injectable nanospheres was evaluated against mouse fibroblast L929 cell line and
      human polymorphonuclear cells by methlythiazolyltetrazolium assay. As far as
      particle size and zeta potential are concerned, there is a relationship between
      surfactant presence and nanoparticle characteristics. However, these effects are
      not significant. It was also found that surfactant presence has no effect on
      model drug nimodipine encapsulation but accelerates the in-vitro release of the
      drug. Cell culture studies on mouse fibroblasts and human polymorphonuclear cells
      revealed a concentration-dependent cytotoxicity more pronounced in fibroblast
      cells. This led to the conclusion that the use of surfactants in injectable
      nanoparticles prepared from amphiphilic beta-cyclodextrins may lead to altered in
      vitro properties and impaired safety for the drug delivery system.

PMID- 16640827
TI  - Modulation of gastrointestinal permeability of low-molecular-weight heparin by L
      arginine: in-vivo and in-vitro evaluation.
AB  - L-Arginine is the principal physiological precursor of nitric oxide (NO, a key
      neurotransmitter) that plays a versatile role in the physiology of the
      gastrointestinal tract. In this study, the efficacy of L-arginine in enhancing
      intestinal absorption of ardeparin, a low-molecular-weight heparin (LMWH) was
      investigated in Caco-2 cell monolayers and a rat model. Regional permeability
      studies using rat intestine were performed using a modified Ussing chamber. Cell
      viability in the presence of various concentrations of enhancer was determined by
      MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically
      evaluated. LMWH formulated with L-arginine was administered orally to male
      Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma
      anti-factor Xa activity. Higher ardeparin in-vitro permeability (approximately 3
      fold) compared with control was observed in the presence of 2% L-arginine.
      Regional permeability studies indicated predominant absorption in the colon
      region. Cell viability studies showed no significant cytotoxicity below 0.8% L
      arginine. The oral bioavailability of ardeparin formulated with L-arginine (250
      mg kg(-1)) was increased by approximately 2 fold compared with control. The
      formulation was well tolerated by the rats and no abnormal histopathological
      findings were observed in intestinal tissues of rats exposed to L-arginine. These
      results suggest that L-arginine may be useful in enhancing the intestinal
      absorption of LMWHs.

PMID- 16640828
TI  - Transdermal delivery of (-)-epigallocatechin-3-gallate, a green tea polyphenol,
      in mice.
AB  - Epigallocatechin-3-gallate (EGCG) is the most studied catechin in green tea
      (Camellia sinensis). EGCG and green tea are cancer preventive in many animal
      models, and numerous mechanisms have been proposed in cell lines. EGCG is poorly
      bioavailable in man and rodents. We hypothesized that transdermal delivery of
      EGCG could result in improved bioavailability. Following application of EGCG
      transdermal gel (50 mg kg(-1), t.d.) to SKH-1 mice, EGCG was observed in the
      epidermis (1365.7-121.0 ng g(-1)) and dermis (411.2-42.6 ng g(-1)). The maximum
      plasma concentration (Cmax) of EGCG was 44.5 ng mL(-1). The t(1/2) (94.4 h) and
      AUC(0-->24 h) (881.5 ng mL(-1) h) of EGCG were greater than values previously
      reported for oral EGCG. The t(1/2) and area under the concentration-time curve up
      to 24 h (AUC(0-->24 h)) in the liver, small intestine and colon were 21.3-74.6 h
      and 715-2802 ng g(-1)h, respectively. Stability studies showed that the
      transdermal formulation was stable at 4 degrees C and had a half-life (t(1/2)) of
      47.1 and 20.2 h at 25 degrees C and 37 degrees C, respectively. These data
      indicate that transdermal EGCG is useful for delivering prolonged levels of EGCG
      to plasma and tissues, and may provide an alternative to tea consumption as a
      dosage form of EGCG.

PMID- 16640829
TI  - Stavudine-loaded mannosylated liposomes: in-vitro anti-HIV-I activity, tissue
      distribution and pharmacokinetics.
AB  - Cells of the mononuclear phagocyte system (MPS) are important hosts for human
      immunodeficiency virus (HIV). Lectin receptors, which act as molecular targets
      for sugar molecules, are found on the surface of these cells of the MPS.
      Stavudine-loaded mannosylated liposomal formulations were developed for targeting
      to HIV-infected cells. The mannose-binding protein concanavalin A was employed as
      model system for the determination of in-vitro ligand-binding capacity.
      Antiretroviral activity was determined using MT-2 cell line. Haematological
      changes, tissue distribution and pharmacokinetic studies of free, liposomal and
      mannosylated liposomal drug were performed following a bolus intravenous
      injection in Sprague-Dawley rats. The entrapment efficiency of mannosylated
      liposomes was found to be 47.2 +/- 1.57%. Protein-carbohydrate interaction has
      been utilized for the effective delivery of mannosylated formulations. Cellular
      drug uptake was maximal when mannosylated liposomes were used. MT2 cells treated
      continuously with uncoated liposomal formulation had p24 levels 8-12 times lower
      than the level of free drug solution. Further, the mannosylated liposomes have
      shown p24 levels that were 14-20 and 1.4-2.3 times lower than the level of free
      drug and uncoated liposomal formulation treatment, respectively. Similar results
      were observed when infected MT2 cells were treated overnight. Stavudine, either
      given plain or incorporated in liposomes, led to development of anaemia and
      leucocytopenia while mannosylated liposomes overcame these drawbacks. These
      systems maintained a significant level of stavudine in the liver, spleen and
      lungs up to 12 h and had greater systemic clearance as compared with free drug or
      the uncoated liposomal formulation. Mannosylated liposomes have shown potential
      for the site-specific and ligand-directed delivery systems with desired
      therapeutics and better pharmacological activity.

PMID- 16640830
TI  - Preventive effect of S-allyl cysteine sulfoxide (alliin) on cardiac marker
      enzymes and lipids in isoproterenol-induced myocardial injury.
AB  - The present study was designed to evaluate the preventive effect of S-allyl
      cysteine sulfoxide (SACS) in isoproterenol (ISO)-induced myocardial ischaemia in
      male Wistar rats. Rats were pretreated with SACS (40 and 80 mg kg(-1) body
      weight) for 5 weeks. After the treatment period, ISO (150 mg kg(-1) body-weight)
      was administered subcutaneously to rats at intervals of 24 h for 2 days. The
      activities of creatine kinase, creatine kinase-MB, lactate dehydrogenase,
      aspartate transaminase and alanine transferase were significantly increased in
      serum and significantly decreased in the hearts of ISO-treated rats. Pretreatment
      with SACS decreased the activities of these enzymes significantly in serum and
      significantly increased the activities in heart in ISO-treated rats. The levels
      of cholesterol, triglycerides and free fatty acids increased in serum and heart,
      while the levels of phospholipids increased in serum and decreased in heart in
      ISO-treated rats. SACS pretreatment showed a significant effect on the lipids
      studied. The activity of 3-hydroxy 3-methyl glutaryl coenzyme A (HMG CoA)
      reductase was significantly increased and the activity of lecithin cholesterol
      acyl transferase (LCAT) was significantly reduced in ISO-induced rats. Oral
      pretreatment with SACS significantly decreased the activity of HMG CoA reductase
      and significantly increased the activity of LCAT in ISO-induced rats. The levels
      of plasma thiobarbituric acid reactive substances and hydroperoxides were
      increased in ISO-treated rats. Pretreatment with SACS significantly decreased the
      levels of lipidperoxides in ISO-treated rats. The effect at a dose of 80 mg kg(
      1) body-weight was more effective than at a dose of 40 mg kg(-1) body-weight and
      brought back all the biochemical parameters to near normal levels. Thus our study
      shows that SACS has a lipid-lowering effect in ISO-induced rats. Our study may
      have clinical relevance.

PMID- 16640831
TI  - Evaluation of the free-radical-scavenging activity of diclofenac acid on the free
      radical-induced haemolysis of human erythrocytes.
AB  - Free-radical-induced peroxidation in-vivo is regarded as the aetiology of some
      diseases and free-radical-scavenging drugs, also called antioxidants (AH), have
      been widely used to overcome oxidative stress. An in-vitro experimental method,
      2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced haemolysis of human
      erythrocytes can be applied to assess the free-radical-scavenging activity of a
      drug. The major objectives of this work were focused on three aspects. Firstly,
      introduction of the chemical kinetic deduction of free-radical-initiating
      reaction to AAPH-induced haemolysis of human erythrocytes, by which the number of
      free radicals trapped by an antioxidant, n, can be obtained after finding the
      quantitative relationship between the inhibition period (t(inh)) and the
      concentration of the antioxidant, t(inh) = (n/Ri) [AH]. Ri, the free-radical
      initiating rate, was initially confirmed by using alpha-tocopherol (VE) whose n
      was taken as 2. Secondly, the free-radical-scavenging activity of diclofenac acid
      (DaH) and its sodium salt (DaNaH) was assessed. It has been found that DaH and
      DaNaH protect human erythrocytes against AAPH-induced haemolysis dose
      dependently. In particular, the n values of DaH and DaNaH (4.96 and 3.60) were
      much higher than some traditional antioxidants, such as 6-hydroxyl-2,5,7,8
      tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble structural analogue
      of VE, n = 0.30) and L-ascorbic acid (VC, n = 0.25), and L-ascorbyl-6-laurate (VC
      12, a lipophilic structural analogue of VC, n = 1.11). Moreover, the free-radical
      scavenging activity of lipophilic antioxidants is higher than the corresponding
      water-soluble species. Thirdly, the free-radical-scavenging activity of mixed
      antioxidants, VE + DaH, VC-12 + DaH, Trolox + DaNaH and VC + DaNaH, was revealed.
      The n value of VC, VC-12, VE and Trolox increase in the case of mixed usage with
      DaH and DaNaH, implying that diclofenac acid can repair the radical of these
      antioxidants. Thus, a mutual antioxidant effect between diclofenac acid and these
      antioxidants prolongs the lifespan of VC, VC-12, VE and Trolox, respectively.

PMID- 16640832
TI  - Prediction of hepatic clearance using cryopreserved human hepatocytes: a
      comparison of serum and serum-free incubations.
AB  - Cryopreserved human hepatocytes have been used to predict hepatic in-vivo
      clearance. Physiologically-based direct scaling methods generally underestimate
      human in-vivo hepatic clearance. Cryopreserved human hepatocytes were incubated
      in 100% serum and in serum-free medium to predict the in-vivo hepatic clearance
      of six compounds (phenazone (antipyrine), bosentan, mibefradil, midazolam,
      naloxone and oxazepam). Monte Carlo simulations were performed in an attempt to
      incorporate the variability and uncertainty in the measured parameters to the
      prediction of hepatic clearance. The intrinsic clearance (CL(int)) and the
      associated variability of the six compounds decreased in the presence of serum
      and the values were reproducible across donors. The predicted CL(hep, in-vivo)
      obtained with hepatocytes from donors incubated in serum was more accurate than
      the prediction obtained in the absence of serum. For example, the CL(hep, in
      vivo) of mibefradil in donor GNG was 4.27 mL min(-1) kg(-1) in the presence of
      serum and 0.46 mL min(-1) kg(-1) in the absence of serum (4.88 mL min(-1) kg(-1)
      observed in-vivo). Using the results obtained in this study together with an
      extended data set (26 compounds), the clearance of 77% of the compounds was
      predicted within a 2-fold error in the absence of serum. In the presence of
      serum, 85% of the compounds were successfully predicted within a 2-fold error. In
      conclusion, cryopreserved human hepatocyte suspensions represented a convenient
      and predictive model to assess human drug clearance.

PMID- 16640833
TI  - Mechanism for increased bioavailability of tacrine in fasted rats.
AB  - The mechanism associated with the increased bioavailability of tacrine as a
      result of a 24-h period of fasting was examined in rats. The AUC value for
      tacrine after the fasting was 52% higher compared with normal feeding when 4 mg
      kg(-1) of tacrine was orally administered, but the value for velnacrine, a
      hydroxylated metabolite of tacrine, was reduced by 10%. The relative metabolic
      ratio of tacrine in urinary excretion (Au(tacrine) divided by Au(velnacrine)) was
      lower in fasted rats compared with normally fed rats. This clearly shows that
      metabolism of tacrine is reduced with 24-h fasting after oral administration.
      Altered intestinal permeation in the fasting state was hypothesized, and the
      transport of tacrine across the rat intestine was studied. When a fasted
      intestine was mounted in an Ussing chamber, the mucosal-to-serosal permeability
      of tacrine was increased to double that for a fed rat intestine. To examine the
      effect of absorption rate on the hepatic metabolism of tacrine, a direct pyloric
      vein infusion study was carried out. Compared with an infusion of tacrine for 5
      min, a slow infusion of tacrine over a period of 30 or 60 min increased the
      hepatic metabolism of tacrine and decreased its systemic clearance in rats.
      Collectively, these results suggest that rapid transport across the intestine
      aids tacrine in avoiding hepatic first-pass metabolism and enhances its
      bioavailability in fasted rats. From these findings, we conclude that both oral
      administration before a meal and a reduction in the dose might be recommended in
      tacrine therapy considering the serious hepatotoxicity of tacrine in clinical
      use.

PMID- 16640834
TI  - Docosahexaenoic acid (DHA) inhibits saquinavir metabolism in-vitro and enhances
      its bioavailability in rats.
AB  - This study investigated the effect of docosahexaenoic acid (DHA) on the
      metabolism of saquinavir by cytochrome P450 3A (CYP3A) in-vitro using rat liver
      microsomes and in-vivo using rats. DHA showed a concentration-dependent
      inhibition of in-vitro saquinavir metabolism with Km, Vmax and Ki values of 2.21
      microM, 0.054 micromol h(-1) (mg protein)(-1) and 149.6 microM, respectively.
      After oral co-administration with 250 microg kg(-1) DHA, the bioavailability of
      saquinavir significantly increased approximately 4 fold (P < 0.01) without
      affecting the elimination half-life, as compared with the control. In contrast,
      oral administration of DHA did not affect the kinetic parameters of saquinavir
      administered intravenously. These results suggest that the inhibitory effect of
      DHA on saquinavir metabolism predominantly takes place in the gut and imply that
      DHA impairs the function of enteric, but not of hepatic, CYP3A. The
      pharmacokinetic interaction occurred only when DHA was taken simultaneously with
      oral administration of saquinavir. These results considered together with the
      lack of time-dependent saquinavir metabolism inactivation effects in-vitro, imply
      that the inhibitory effect of DHA is primarily reversible. It is concluded that
      DHA inhibited saquinavir metabolism in-vitro and enhanced the oral
      bioavailability of saquinavir in rats.

PMID- 16640835
TI  - Water-soluble extract of Salvia miltiorrhiza ameliorates carbon tetrachloride
      mediated hepatic apoptosis in rats.
AB  - Apoptosis is one of the events that are involved in liver fibrogenesis. Thus,
      factors that affect apoptosis may be used to modulate liver fibrosis. We have
      recently reported that Salvia miltiorrhiza plays a protective role in carbon
      tetrachloride (CCl4)-induced hepatic fibrosis. In this study, we aimed to
      evaluate whether S. miltiorrhiza modulated CCl4-induced hepatic apoptosis in
      rats. Male Wistar rats were given orally either vehicle or water-extract of S.
      miltiorrhiza (50 mg kg(-1) twice daily) for nine weeks beginning from the start
      of CCl4 administration. A group of normal rats was included for comparison.
      Hepatocyte DNA fragmentation and cytosolic caspase-3 and caspase-8 activity were
      determined in the experimental animals. Hepatic cytosolic Bax, Bcl-2, cytochrome
      c, and calpain-mu expressions were measured by Western blot analysis. Hepatic
      mitochondrial glutathione levels were assessed by colorimetric assay. Compared
      with normal rats, rats receiving CCl4 alone showed profound DNA fragmentation
      associated with an increased cytosolic fraction of cytochrome c and calpain-mu
      protein expressions and a decreased mitochondrial glutathione level. In contrast,
      a decreased laddering of DNA fragmentation was noted in rats receiving CCl4 plus
      S. miltiorrhiza extract. The mitochondrial glutathione level was significantly
      increased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those
      receiving CCl4 alone. Additionally, cytosolic caspase-3 activity and cytosolic
      fractions of Bax, Bcl-2, cytochrome c, and calpain-mu protein expressions were
      decreased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those
      receiving CCl4 alone. The cytosolic caspase-8 activity in rats receiving CCl4
      alone was no different from those receiving CCl4 plus S. miltiorrhiza extract.
      These results indicated that chronic administration of S. miltiorrhiza
      ameliorated CCl4-mediatd hepatic apoptosis in rats. This effect may be related to
      the antioxidant properties of S. miltiorrhiza.

PMID- 16640836
TI  - Involvement of the nitric oxide/soluble guanylate cyclase pathway in the anti
      oedematogenic action of Pfaffia glomerata (Spreng) Pedersen in mice.
AB  - Pfaffia glomerata is used in southern American countries against inflammatory
      diseases. We have explored the ability of a crude hydroalcoholic extract of P.
      glomerata root (HEPG) to prevent the oedematogenic action of several inflammatory
      agents in mice. We have examined also the duration of its effects and the
      mechanisms involved. The oral or intraperitoneal treatment of mice with HEPG (1,
      10, 30, 100 or 300 mg kg(-1)) reduced, in a dose-dependent manner, carrageenan
      induced paw oedema in the early (1-4 h) and late (48 h) periods. In the early
      period, the ID50 value (the median dose that caused 50% inhibition) of HEPG was
      60.5 (28.5-128.71) and 20.4 (14.8-28.3) mg kg(-1) after oral and intraperitoneal
      administration, respectively. This effect was still evident when HEPG was
      administered up to 6 h before carrageenan. HEPG inhibited also paw oedema induced
      by histamine, serotonin, bradykinin, substance P and bacterial
      lipopolysaccharide. In addition, oral administration of HEPG increased the levels
      of nitrate and nitrite in the blood of mice. Further, its anti-oedematogenic
      action against carrageenan was prevented fully by N(G) nitro-L-arginine-methyl
      ester (10 mg kg(-1), s.c.), as well as by methylene blue (20 mg kg(-1), s.c.) or
      1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (2 mg kg(-1), s.c.). The results
      indicated that stimulation of endogenous production of nitric oxide, followed by
      soluble guanylate cyclase activation, was implicated in the anti-oedematogenic
      action of HEPG.

PMID- 16640837
TI  - Aqueous extract of Yin-Chen-Hao decoction, a traditional Chinese prescription,
      exerts protective effects on concanavalin A-induced hepatitis in mice through
      inhibition of NF-kappaB.
AB  - In traditional oriental medicine, Yin-Chen-Hao decoction is used for the remedy
      of liver diseases such as hepatitis, fatty liver, hepatocirrhosis and jaundice.
      However, despite extensive pharmacological study, the molecular mechanism of the
      anti-inflammatory effect of Yin-Chen-Hao decoction is poorly understood. In this
      study, we have investigated the pharmacological action on the mechanism of
      concanavalin A-induced T cell-dependent hepatitis in mice. Concanavalin A
      administration resulted in a severe liver injury. This was shown through
      increased levels of serum transaminase and lactic dehydrogenase, and increased
      liver DNA fragmentation and caspase-3 activity. Pretreatment with the aqueous
      extract from Yin-Chen-Hao decoction dose-dependently inhibited the elevation in
      transaminase and lactic dehydrogenase activity, and reduced liver DNA
      fragmentation and caspase-3 levels. There was an improvement in histological
      changes including inflammatory infiltration, hepatocyte necrosis and
      degeneration, and Kupffer cell hyperplasia. In addition, Yin-Chen-Hao decoction
      significantly inhibited tumour necrosis factor-alpha (TNF-alpha) production in
      vitro and in-vivo. Moreover, the activation of nuclear factor kappa B (NF
      kappaB), which regulates TNF-alpha production, was blocked by Yin-Chen-Hao
      decoction in-vitro and in-vivo. In conclusion, Yin-Chen-Hao decoction was capable
      of regulating T-cell-mediated liver injury in-vivo. This event may have depended
      on the decrease of TNF-alpha production through the inhibition of NF-kappaB
      activation.

PMID- 16640838
TI  - The pharmacological potential of Sorbus commixta cortex on blood alcohol
      concentration and hepatic lipid peroxidation in acute alcohol-treated rats.
AB  - The effect of Sorbus commixta cortex, a traditional herbal medicine used for the
      treatment of bronchitis, gastritis and dropsy, on blood alcohol concentration
      (BAC) and hepatic lipid peroxidation was examined in acute alcohol-treated rats.
      A 30-min pretreatment with a methanol extract of S. commixta cortex (SC) at
      concentrations higher than 200 mg kg(-1) resulted in a significant decrease in
      BAC and the ethyl acetate fraction (SE) of the extract showed the highest
      potency, with a maximum of a 46% decrease at 150 mg kg(-1) 2 h after alcohol
      administration (3.0 g kg(-1)) compared with the control group (P < 0.005). The
      rapid reduction in BAC did not appear to be due to the protection or activation
      of hepatic alcohol dehydrogenase (ADH) activity by SE. Hepatic malondialdehyde
      (MDA) levels were significantly increased by acute alcohol administration within
      6 h, although pretreatment with the SE caused a significant decrease in MDA
      levels compared with alcohol treatment alone. Hepatic glutathione (GSH) levels
      and superoxide dismutase (SOD) activity remained unchanged by alcohol, SE alone
      or by the combined treatment of alcohol and SE. However, catalase activity was
      significantly reduced by acute alcohol administration and pretreatment with the
      SE led to significant protection of its activity. These results suggest that
      pretreatment with SE reduces hepatic lipid peroxidation by decreasing the
      bioavailability of alcohol and its oxidative metabolites, such as H2O2, at least
      partly, through the protection of hepatic catalase in acute alcohol-treated rats.

PMID- 16640839
TI  - Acetylcholinesterase inhibitors from Stephania venosa tuber.
AB  - Acetylcholinesterase (AChE) inhibitors have lately gained interest as potential
      drugs in the treatment of Alzheimer's disease. Three AChE inhibitors were
      isolated from tubers of a Thai medicinal plant, Stephania venosa (Bl) Spreng.
      They were identified as quaternary protoberberine alkaloids, stepharanine,
      cyclanoline and N-methyl stepholidine. They expressed inhibitory activity on AChE
      with IC50 values (concentration that caused 50% inhibition of activity) of 14.10
      +/- 0.81, 9.23 +/- 3.47 and 31.30 +/- 3.67 microM, respectively. The AChE
      inhibitory activity of these compounds was compared with those of the related
      compounds, palmatine, jatrorrhizine and berberine, as well as tertiary
      protoberberine alkaloids isolated from the same plant, stepholidine and
      corydalmine. The results suggest that the positive charge at the nitrogen of the
      tetrahydroisoquinoline portion, steric substitution at the nitrogen, planarity of
      the molecule or substitutions at C-2, -3, -9, and -10 affect the AChE inhibitory
      activity of protoberberine alkaloids.

PMID- 16640840
TI  - Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants
      in isoproterenol-induced myocardial infarction in rats.
AB  - The consumption of diets rich in plant foods is associated with a reduced risk of
      cardiovascular diseases. This study aimed to evaluate the preventive role of
      rutin on lipid peroxides and antioxidants in normal and isoproterenol-induced
      myocardial infarction in rats. Subcutaneous injection of isoproterenol (150 mg
      kg(-1)) to male Wistar rats at an interval of 24 h for two days showed a
      significant increase in the activity of serum cardiac marker enzymes (creatine
      kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase)
      and a significant decrease in the activity of these enzymes in the heart. Lipid
      peroxidative products (thiobarbituricacid reactive substances and lipid
      hydroperoxides) were significantly increased and enzymic (superoxide dismutase,
      catalase and glutathione peroxidase) and non-enzymic (reduced glutathione and
      vitamin C) antioxidants showed a significant decrease in isoproterenol-treated
      rats. Pretreatment with rutin (40 or 80 mg kg(-1)) to isoproterenol-treated rats
      orally for a period of 42 days daily caused a significant effect. Administration
      of rutin to normal rats did not have any significant effect on any of the
      parameters studied. The results of our study show that rutin possesses
      antioxidant activity in isoproterenol-induced experimental myocardial infarction.

PMID- 16640841
TI  - Influence of propolis water solution on heart mitochondrial function.
AB  - The effect of propolis water solution (PWS) on the respiration of rat heart
      mitochondria with NAD-linked (pyruvate + malate), FAD-linked (succinate)
      substrates and fatty acids (palmitoyl-L-carnitine) was investigated in this
      study. PWS at the lowest concentration of 4 microg mL(-1) of phenolic compounds
      (PC) had no effect on mitochondrial respiration with all investigated substrates.
      PWS at concentrations of 63 and 125 microg mL(-1) of PC caused a significant
      decrease of basal (24 and 54%) and maximal (58 and 70%) respiration rates with
      succinate as substrate. At these PWS concentrations the oxidation of pyruvate +
      malate and palmitoyl-L-carnitine was diminished to a lower degree: the basal
      respiration rate decreased by 13-18% and the maximal respiration rate by 15-28%.
      Succinate oxidation was affected, probably because of the inhibition of succinate
      dehydrogenase by the 1,2-benzenedicarboxylic acid esters found in PWS. The PWS
      caused decrease in the mitochondrial respiration rate with pyruvate + malate and
      fatty acids could be due to diminished activities of respiratory chain complexes
      and/or ADP/ATP translocator.

PMID- 16640842
TI  - [Dengue, a growing problem of health in the Americas].

PMID- 16640843
TI  - Assessing HIV resistance in developing countries: Brazil as a case study.
AB  - Increased transmission of resistant HIV has been raised as a potential
      consequence of expanded access to antiretroviral therapy. We review how
      limitations in resources and health care infrastructure may impact the
      transmission of resistant HIV, and we examine data from Brazil as a case study.
      We introduce a biological and clinical framework to identify the major
      determinants of transmitted resistance and to discuss how these determinants may
      be affected by a lack of infrastructure. We then use our framework to examine HIV
      resistance data from Brazil. This country was chosen as a case study due to its
      extensive experience delivering antiretroviral drugs and because of the
      availability of data on the prevalence of resistant HIV there. The data from
      Brazil show that antiretroviral therapy can be delivered in a resource-limited
      setting without resulting in widespread transmission of resistant virus. While
      the Brazilian experience does not necessarily generalize to countries with less
      health care infrastructure, neither theory nor data support a foregone conclusion
      that resistance will necessarily dominate HIV epidemics in the developing world
      to a greater extent than it does in the developed world.

PMID- 16640844
TI  - [Validation of a questionnaire for epilepsy diagnosis in primary care services].
AB  - OBJECTIVE: To evaluate the usefulness of a questionnaire in primary health care
      services for establishing the diagnosis of epilepsy in children from 1 to 10
      years old and for classifying their epileptic seizures. METHODS: This cross
      sectional observational study was conducted in 2004. There were 204 children in
      the study (102 diagnosed with epilepsy and 102 without epilepsy). The children
      were randomly selected at the Regional Center of Epilepsies and the Vincent
      Corral Moscoso Hospital, which are both in the city of Cuenca, Ecuador. For the
      study, each child with epilepsy was matched with a child without epilepsy, in two
      age groups: 1 to 5 years old and 6 to 10 years old. Four students who were in
      their last academic year in the School of Medicine of Cuenca and who did not know
      the child's diagnosis utilized the questionnaire with a family member or other
      guardian of the child. The validity, sensitivity, specificity, positive
      predictive value, and negative predictive value of the questionnaire were
      calculated, with 95% confidence intervals (95% CIs). The clinical diagnosis
      carried out by specialists was used as the gold standard. RESULTS: The assessment
      showed that the questionnaire had good sensitivity (95.10%; 95% CI: 94.58%
      95.61%) and good specificity (97.06%; 95% CI: 96.58%-97.59%). Validity was 96.08%
      (95% CI: 95.84%-96.36%), with a positive predictive value of 97.00% (95% CI:
      96.48%-97.52%) and a negative predictive value of 95.19% (95% CI: 94.74%-95.74%).
      The level of agreement in the classification of the epileptic seizures carried
      out by the neurologists and by the medical students who used the questionnaire
      was satisfactory for the generalized seizures (kappa = 0.67). Upon testing for
      interobserver agreement among the specialists, the kappa value for the diagnoses
      was 0.80 among the neurologists and 0.89 among the pediatricians. CONCLUSIONS:
      The diagnostic questionnaire that was assessed has good sensitivity and adequate
      specificity, and, after brief training, primary health care general practitioners
      can use it to help them diagnose epileptic seizures.

PMID- 16640845
TI  - The mental health status of Mayan refugees after repatriation to Guatemala.
AB  - OBJECTIVE: Only one previous study had examined the epidemiology of mental health
      in Guatemalan refugees. The objective of this new study was to estimate the
      prevalence of mental illness and to assess factors associated with poor mental
      health among Guatemalan Mayan refugees who had been repatriated to Guatemala
      after spending 12-18 years in refugee camps in Mexico, and to compare the results
      for the repatriated Guatemalans with those for Guatemalan refugees who were
      continuing to live in Mexico. METHODS: In 2001 a cross-sectional survey of adults
      (> or = 16 years) was conducted with random household sampling proportional to
      the population size in each of the five repatriation villages surveyed.
      Posttraumatic stress disorder (PTSD), anxiety, and depression were measured by
      the Harvard Trauma Questionnaire and the Hopkins Symptom Checklist-25. RESULTS:
      Together, the five repatriation villages had 565 households. Of the 565
      households, 203 of them were approached to solicit study participation. A total
      of 179 households (one adult per household) agreed to participate, representing
      an overall participation rate of 88%, and one-third of all the households in the
      five communities. The respondents had personally experienced a mean of 5.5 trauma
      events and had witnessed a mean of 7.3 other trauma events. Of the respondents,
      8.9% met the symptom criteria for PTSD, 17.3% for anxiety, and 47.8% for
      depression. PTSD was associated with being seriously wounded and with having
      relatives or friends mutilated. Logistic regression analyses indicated that
      anxiety was associated with being sexually assaulted, being female, having
      friends or family mutilated, being seriously wounded, and having 6-12 children
      (vs. having 1-5 children). Depression was associated with having 6-12 children.
      Anxiety was significantly more prevalent among the refugees remaining in Mexico
      (54.4%) than it was among the repatriated refugees (17.3%). The difference in the
      prevalence rates was not significant for PTSD (11.8% for refugees remaining in
      Mexico vs. 8.9% for those repatriated) or for depression (38.8% for refugees
      remaining in Mexico vs. 47.8% for those repatriated). CONCLUSIONS: Psychiatric
      morbidity was common among the repatriated Mayans. The repatriation of refugees
      involves moving an already vulnerable, often traumatized population back to a
      place of distressing memories and still-unsettled conditions. There is a need to
      consider and plan for adequate mental health services for repatriating refugees.

PMID- 16640846
TI  - [Epidemiologic surveillance of measles and rubella in Campinas (SP), Brazil: the
      reliability of the data].
AB  - OBJECTIVE: To evaluate and validate the information concerning measles and
      rubella from the Brazilian National Disease Notification System (BNDNS) (Sistema
      Nacional de Informacao de Agravos de Notificacao, or SINAN) for Campinas, a large
      city in the state of Sao Paulo, Brazil, using as a reference the data from a
      control system, the Syndromic Surveillance System for Fever and Exanthem (SSSFE)
      (Sistema de Vigilancia Sindromica de Febre e Exantema, or VigiFEx), which
      operated from May 2003 through June 2004. METHOD: In our study we compared: (1)
      annual data from BNDNS for the years 1999 through 2003 and (2) data from BNDNS
      and data from SSSFE for the period of June 2003 through May 2004. We analyzed the
      rate of completion for key fields (record number, date of notification, and city
      of notification) as well as for name of disease, date of first symptoms, name of
      patient, birth date and age, sex, city of residence, date of investigation,
      immunization history, presence of exanthem, date at start of exanthem, presence
      of fever, suspected cases among pregnant women, signs and symptoms, date of
      collection of first sample, results with the sample, virus isolation, final
      classification, criteria for confirmation/exclusion of cases, diagnosis of
      excluded patients, development of the case, and date of closure. The level of
      agreement between the recorded cases in the two data banks was also analyzed.
      RESULTS: From June 2003 through May 2004, 211 suspected cases of measles or
      rubella were identified in SSSFE and 275 in BNDNS. All the records had complete
      information concerning the three key fields. The rate of completion was also 100%
      for patient name, disease, and city of residence. The completion rate was higher
      than 95% for date of investigation, measles vaccine, measles and rubella vaccine,
      and rubella vaccine. A lower completion rate was found for other vaccination
      variables (number of doses and date of last dose) and for exanthem, fever, and
      date of start of exanthem. The two information systems were not completely
      consistent, particularly in terms of variables related to epidemiologic
      background, clinical data, and case closure. The quality of the SSSFE data was
      higher. CONCLUSIONS: Epidemiologic surveillance, immunization, and laboratory
      information systems need to undergo routine evaluation to ensure that the data
      are reliable and can support the planning of public health efforts.

PMID- 16640847
TI  - A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of
      infants in Latin America.
AB  - OBJECTIVES: In 1998 the World Health Organization (WHO) recommended the inclusion
      of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization
      programs, whenever in accordance with national priorities. GlaxoSmithKline
      Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole
      cell pertussis-hepatitis B/Hib (DTPw-HB/Hib) vaccine containing 5 microg of
      polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and
      reactogenicity of primary and booster vaccination of healthy children with this
      new vaccine compared with a reference regimen consisting of the licensed DTPw-HB
      (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant
      injections. METHODS: We performed a randomized, double-blind study from September
      1998 to August 1999 to establish the immunogenicity and reactogenicity of primary
      and booster vaccination of healthy children with the new pentavalent combined
      DTPw-HB/Hib vaccine given as a single injection, compared with the reference
      regimen. RESULTS: Both vaccination regimens elicited excellent immune responses,
      with all subjects in both groups achieving seroprotective anti-PRP antibody
      concentrations of > or = 0.15 microg/mL one month after primary vaccination. The
      combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms
      of seroprotection/seropositivity/vaccine response rates for all antigen
      components. Persistence of antibodies against all study vaccine antigens up to
      the time of booster vaccination was comparable between groups, and a marked
      increase of all antibody concentrations was observed after the booster dose. Both
      vaccine regimens were similar in terms of their overall reactogenicity profiles.
      CONCLUSIONS: Our results indicate that the new DTPw-HB/Hib pentavalent
      combination vaccine provides an efficient and reliable way of implementing WHO
      recommendations for controlling hepatitis B and Hib infections on a worldwide
      basis.

PMID- 16640848
TI  - [Genomic risk and personal responsibility in health].
AB  - With the advent of genomic research, a new category of risk has emerged--genetic
      risk--from which an individual cannot be separated. Among the outcomes of this
      model is a discussion on personal accountability, according to which an
      individual may both be exempted from events related to certain states of health
      ("blame it on the genes") or be blamed for those events ("transmitter of
      disease"). In addition, the search for genes to explain disease erases the line
      between what is normal and what is pathological, with a growing tendency towards
      considering individuals with no or very mild clinical manifestations as being
      "ill." The great emphasis on genomics may lead to both an exaggerated attention
      to genetics rather than social and environmental factors and to a reductionism
      that favors sociobiological explanations for human behavior. In addition, in this
      scenario, the right to information may paradoxically stimulate some to consume
      goods and services in order to prevent a hypothetical illness that could occur at
      some point in time as a result of genetic predisposition-goods and services that
      may not be available to everyone. It is essential that such issues be considered
      with the same urgency with which the genomic paradigm is being developed.

PMID- 16640849
TI  - [Dengue and dengue hemorrhagic fever: research priorities].
AB  - Dengue is one of the most important infectious diseases in tropical and
      subtropical countries. At present, the only strategy available to reduce the
      incidence of dengue is vector control. The World Health Organization and the Pan
      American Health Organization have called on all nations to take the needed steps
      to help diminish the burden of this disease and its medical and socioeconomic
      impact. It is hoped that it will be possible to reverse the increase in dengue
      and help control its spread through a coordinated, effective international
      response, along with epidemiological, clinical, and virological research that
      brings together the most advanced methods and techniques. This piece summarizes
      the most up-to-date information on dengue, analyzes current epidemiologic trends
      in the Region of the Americas, discusses the main global and Western Hemisphere
      initiatives to control the disease, and presents the main areas of research that
      should be developed in the immediate future.

PMID- 16640850
TI  - [Reasonable applications of chemotherapy in gynecological malignancy].

PMID- 16640853
TI  - [Neoadjuvant chemotherapy before radiotherapy in treatment of patients with
      cervical carcinoma].
AB  - OBJECTIVE: To study the value of neoadjuvant chemotherapy in treatment of
      cervical carcinoma. METHODS: A clinical prospective study was carried out from
      Jan 1991 to Dec 2003. Totally 1609 patients with cervical carcinoma were given
      two cycles of combined chemotherapy before radiotherapy (neoadjuvant chemotherapy
      group, group A). Another 375 patients who accepted radiotherapy alone in our
      hospital from Jan 1989 to Dec 1990 were chosen as the control group (group B).
      Short-term control rate, long-term survival rate and complications were observed
      and analyzed. RESULTS: In group A, after two cycles of neoadjuvant chemotherapy,
      the overall response rate was 74.5% (1199/1609), the complete response rate was
      1.6% (25/1609). The survival rate of 3, 5 and 10-year was 90.3% (1017/1126),
      75.3% (652/866), and 59.0% (200/339), respectively. Five-year survival rate in
      stage II was higher than that in stage III (P < 0.05), but 3-year and 10-year
      survival rate were not different between stages II and III (P > 0.05). In group
      B, 3, 5 and 10-year survival rate was 81.1% (304/375), 59.2% (222/375), and 40.3%
      (151/375), respectively. The 5-year and 10-year survival rate was significantly
      higher in stage II than that in stage III (P < 0.05). The 5 and 10-year survival
      rate was significantly higher in group A than that in group B (P < 0.05). The 3,
      5 and 10-year survival rate of patients with adenocarcinoma in group A was
      obviously higher than that in group B (P < 0.05), and the 3 and 5-year recurrent
      and metastatic rate was significantly lower in group A than that in group B (P <
      0.05). In group A, the short-term toxicity and side-effect of neoadjuvant
      chemotherapy were mainly slight and moderate, and the short-term and long-term
      radiation complications had no obvious difference between two groups (P > 0.05).
      CONCLUSIONS: Neoadjuvant chemotherapy is a safe and effective method for the
      treatment of cervical carcinoma. Because of satisfactory short-term control rate
      and high long-term survival rate, neoadjuvant chemotherapy should be popularized
      in clinical treatment, especially in those patients with adenocarcinoma and in
      patients at clinically advanced stage of cervical carcinoma.

PMID- 16640854
TI  - [Efficacy of FAEV regimen in treatment of high-risk drug-resistant gestational
      trophoblastic tumor].
AB  - OBJECTIVE: To evaluate the efficacy of floxuridine, actinomycin D, etoposide,
      vincristine (FAEV) regimen in treatment of high-risk drug-resistant gestational
      trophoblastic tumor (GTT). METHODS: From October 2001 to May 2004, 11 cases of
      high-risk drug-resistant GTT were treated with FAEV regimen. The International
      Federation of Gynecology and Obstetrics (FIGO) prognosis score (2000) was 7 to 13
      (median 9). All patients were referred to Peking Union Medical College Hospital
      because of failure of chemotherapy previously. After the FAEV treatment, they
      were followed up for 15 to 42 months. RESULTS: Seven cases (64%, 7/11) were cured
      by FAEV regimen. The median treatment course for serum human chorionic
      gonadotropin reaching normal level was 3. Four cases (36%, 4/11) showed drug
      resistant to FAEV regimen. The major side effect of FAEV regimen was
      myelosuppression. Granulocyte colony stimulating factor support was needed after
      98% (63/64) of the courses. CONCLUSION: For those high-risk drug-resistant GTT
      cases, FAEV regimen could be considered as an effective choice of treatment.

PMID- 16640855
TI  - [Relationship between CA125 half life during neoadjuvant chemotherapy and the
      optimal operation rate and prognosis in patients with advanced epithelial ovarian
      carcinoma].
AB  - OBJECTIVE: To investigate the relationship between the serum half life of CA(125)
      and the optimal operation rate and prognosis in patients with advanced epithelial
      ovarian carcinoma treated with neoadjuvant chemotherapy. METHODS: Clinical data
      of 39 patients who had undergone neoadjuvant chemotherapy were analyzed
      retrospectively. Patients were divided into two groups according to the serum
      half-life of CA(125), and the optimal operation rate and prognosis were compared.
      RESULTS: The optimal operation rate in patients with serum half-life >or= 20 days
      was significantly lower than that in patients with serum half-life < 20 days (29%
      vs 80%, P < 0.01). Cumulative survival was higher in patients with serum half
      life < 20 days (P < 0.01). Serum half-life of CA(125) and tumor residual after
      operation were independent prognostic factors by COX model analysis. CONCLUSION:
      Serum half-life of CA(125) may indicate optimal debulking operation, and it is an
      independent prognostic factor in ovarian carcinoma patients treated with
      neoadjuvant chemotherapy.

PMID- 16640856
TI  - [Evaluation of neoadjuvant chemotherapy for locally advanced cervical cancinoma].
AB  - OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on locally
      advanced cervical cancer, the factors affecting outcome of chemotherapy and the
      long-term survival rate in the patients. METHODS: A total of 64 patients with
      stageIb2-IIb of locally advanced cervical cancers treated with neoadjuvant
      chemotherapy between June 1999 and October 2004 in Women's Hospital, School of
      Medicine, Zhejiang University were retrospectively analysed. The effect of
      chemotherapy, as well as survival rate was evaluated. The related factors of
      effect, including age, histology, clinical stage, grade of differentiation,
      initial tumor size, chemotherapy regimens, number of courses were analysed.
      RESULTS: Overall effective rate of neoadjuvant chemotherapy was 80%. The
      effective rate was associated with histology. The patients with squamous cell
      cancer had significantly higher 5-year survival rate than those with
      adenocarcinoma (82% vs 6/9, P < 0.05). The rates of positive pelvic lymph node
      metastasis and parametrial invasion were significantly higher in complete or
      partial response patients than those in stable patients (P < 0.05). The overall 5
      year survival rate was 89%. The 5-year survival rate in complete or partial
      response group was 100%, in stable disease group was 46% (P < 0.05). The 3, 5
      year disease-free survival rate in complete or partial response group was 95% and
      83%, respectively, while in stable disease group was 33% and 0, respectively. The
      disease-free survival rates in complete or partial response group were higher
      than those of stable disease group (P < 0.05). CONCLUSIONS: The clinical response
      to neoadjuvant chemotherapy is related to histology. The patients who have good
      response to chemotherapy should choose surgery. Chemotherapy can decrease the
      high risk factors of pathology in complete or partial response patients.
      Neoadjuvant chemotherapy for locally advanced cervical cancer patients seems to
      improve the long-term survival rate.

PMID- 16640857
TI  - [Perinatal management and pregnancy outcome in pregnant women with pulmonary
      hypertension complicating cardiac disease].
AB  - OBJECTIVE: To evaluate the pregnancy outcome of women with pulmonary hypertension
      complicating cardiac disease. METHODS: Clinical data of 61 cases of pregnant
      women with pulmonary hypertension from Jan 1996 to Aug 2004 were analyzed and
      they were divided into three groups: 32 cases of slight group [pulmonary
      hypertension from 30 mm Hg (1 mm Hg = 0.133 kPa) to 49 mm Hg], 23 cases of
      moderate group (pulmonary hypertension from 50 mm Hg to 79 mm Hg) and 6 cases of
      severe group (pulmonary hypertension equal to or higher than 80 mm Hg). The types
      of heart disease, cardiac functional status (New York heart association, NYHA),
      gestational weeks of pregnancy termination, mode of delivery and outcomes of
      infants were compared between the groups. RESULTS: (1) The occurrence rate of
      NYHA class III - IV was 5/6 in severe group. The rate of NYHA class I - II was
      72% (23/32) in slight group. (2) The rate of moderate and severe pulmonary
      hypertension was 53% (11/21) and of NYHA class IV 43% (9/21) in rheumatic heart
      disease. The rate of slight pulmonary hypertension was 97% (35/36) and NYHA class
      I - II 81% (29/36) in congenital heart disease. (3) The rate of term delivery was
      75% (24/32) and the birth weight was 2744 g on average in slight group. The rate
      of term delivery was 48% (11/23), preterm labor 35% (8/23), abortion 17% (4/23)
      in moderate group. The rate of term delivery was 1/6, preterm labor occurred in 3
      cases, and abortion in 2 cases in severe group. The rates of neonatal
      complications between the three groups had no significant difference. (4)
      Caesarean section rate was 79% (48/61) among all patients. (5) Overall maternal
      mortality was 2% (1/61). CONCLUSIONS: The rate of heart failure increases
      gradually with the severity of pulmonary hypertension. The severity of pulmonary
      hypertension in rheumatic heart disease is higher than in congenital heart
      disease. The rate of maternal mortality and fetal loss increases in pregnant
      women with pulmonary hypertension complicating cardiac disease. Perinatal
      morbidity is higher than normal. Cesarean section is more suitable for those
      women.

PMID- 16640858
TI  - [Changes of T-helper 1 and T-helper 2 ratio in peripheral blood and decidua in
      hypertensive disorder complicating pregnancy].
AB  - OBJECTIVE: To investigate the role of immune response induced by different T
      helper 1 and T-helper 2 (Th1 and Th2) ratio in peripheral blood and decidua from
      patients with hypertensive disorder complicating pregnancy in the pathogenesis of
      the disease. METHODS: Peripheral blood and decidua from 12 non-pregnant women (no
      deciduas) (normal women group), 12 healthy pregnant women (healthy pregnant women
      group), 10 patients with gestational hypertension (gestational hypertension
      group), 25 patients with pre-eclampsia (PE) (including 10 patients with mild pre
      eclampsia and 15 patients with severe pre-eclampsia) (pre-eclampsia group).
      Th1/Th2 ratio in peripheral blood and decidua was determined by flow
      cytometrically. RESULTS: The ratio of Th1/Th2 in peripheral blood with normal
      women group is 10.5 +/- 1.5, the ratios of Th1/Th2 in peripheral blood and
      deciduas with healthy pregnant women group are 9.5 +/- 2.9 and 7.6 +/- 4.6
      respectively, those with gestational hypertension group are 12.1 +/- 3.4 and 13.1
      +/- 5.6 respectively, those with pre-eclampsia group are 16.8 +/- 3.8 and 26.7 +/
      9.4 respectively. The ratios of Th1/Th2 in peripheral blood and deciduas with
      pre-eclampsia group are much higher than those with other groups, when they are
      compared with each other, there are statistical difference (P < 0.05). And the
      ratio of Th1/Th2 with pre-eclampsia in deciduas is much higher than that in
      peripheral blood, comparing these two aspects, there is statistical difference (P
      < 0.001). The changes of Th1/Th2 ratio in gestational hypertension group is an
      intermediate between healthy pregnant group and pre-eclampsia group. CONCLUSIONS:
      Hypertensive disorder complicating pregnancy is a syndrome of Th1/Th2 cell
      balance disturbances in vivo. Over-expression of Th1 cells and imbalance of
      Th1/Th2 might lead to hypertensive disorder complicating pregnancy.

PMID- 16640859
TI  - [Prospective investigation of postoperative lower extremity deep venous
      thrombosis in gynecological procedures].
AB  - OBJECTIVE: To investigate the morbidity, relevant factors and diagnostic methods
      of lower extremity deep venous thrombosis (LEDVT) after gynecological pelvic
      surgeries. METHODS: A prospective study was carried out investigating the
      morbidity, characteristics, risk factors, the coagulation function changes and
      diagnostic methods of LEDVT post-gynecological pelvic operations in 141 cases.
      Platelet, prothrombin time, activated partial thromboplastin time, fibrinogen,
      thrombin time, D-dimer, antithrombin-III, tissue plasminogen activator,
      plasminogen activator inhibitor were measured within 1 week before surgeries, 48
      hours and 5 - 7 days post-surgeries respectively. Color Doppler flow imaging was
      performed simultaneously. RESULTS: (1) Twenty-two cases were found with LEDVT,
      the morbidity of LEDVT after gynecological procedures was 15.6%. It occurred 2 -
      7 days post operation. (2) The risk factors were bedfasting, coagulant
      prescription post-operation, cardiovascular disease, ageing, pelvic
      lymphadenectomy, general anesthesia, and malignancy. Multivariate regression
      showed only age and coagulant prescription post-operation were independent
      factors. (3) The level of D-dimer was (0.9 +/- 0.6) mg/L in LEDVT group,
      significantly higher than that of non-LEDVT group [(0.5 +/- 0.4) mg/L, P < 0.01].
      The positive predictive value and negative predictive value of D-dimer were 30.8%
      and 98.6% respectively. (4) Among 22 cases who were diagnosed with LEDVT by
      compression duplex ultrasound, only 4 cases performed lower extremity venography,
      and the diagnosis was confirmed. CONCLUSIONS: The morbidity of postoperative
      lower extremity deep venous thrombosis in gynecological procedures was high. The
      combination of D-dimer and compression duplex ultrasound examination was
      applicable to the diagnosis of LEDVT. The optional duration of the examination
      was 2 - 7 days post operations.

PMID- 16640860
TI  - [Visual and histologic analysis of laparoscopic diagnosis of endometriosis].
AB  - OBJECTIVE: To determine the characteristics of anatomical distribution of pelvic
      endometriosis and the correlation between visual and histologic findings of
      endometriosis at laparoscopy. METHODS: A prospective study of 62 patients
      undergoing laparoscopy for the pelvic pain, infertility and/or pelvic masses was
      carried out. All lesions with the diagnosis of endometriosis laparoscopically
      were excised and examined pathologically. Normal-appearing peritoneal biopsies
      were obtained randomly. All lesions were identified by anatomical site and color
      of the foci. The positive predictive value (PPV), sensitivity, negative
      predictive value (NPV), and specificity were determined for visually identified
      endometriosis versus the histologic findings. RESULTS: Totally, 219 peritoneal
      endometriotic lesions, 54 normal peritoneal biopsies, and 71 ovarian
      endometriotic cysts were obtained. Peritoneal lesions tended to locate in
      posterior part of the pelvis (80.8%, 177/219) and in left (58.0%, 127/219) with
      most in black (39.2%). The PPV was 67.6%; sensitivity, 93.7%; NPV, 81.4%; and
      specificity, 38.3% for visual versus histologic diagnosis of peritoneal
      endometriosis. Lesions in black or from sacral ligaments were confirmed
      histologically in 94.2% and 84.7% respectively, and 80.3% (57/71) of ovarian
      endometriotic cysts diagnosed by laparoscopy were confirmed histologically with
      43.6% in the left, 27.3% in the right; and 29.1% (16/55) in both sides of the
      ovary. In addition, 18.5% (10/54) of normal-appearing peritoneal biopsy were
      identified as endometriosis by pathological examination. Laparoscopy was
      confirmed to be in 100% diagnostic accordance with pathology for patients with
      endometriosis. CONCLUSIONS: Our study showed asymmetrical distribution of pelvic
      endometriosis. Peritoneal lesions in black or from sacral ligament are more
      likely to be histologically confirmed, and microscopic lesions are not a rare
      phenomenon of endometriosis.

PMID- 16640861
TI  - [Dynamic assay of serum inhibin B and estradiol concentrations obtained after
      gonadotrophin therapy as predictors of ovarian response in vitro fertilization
      cycle].
AB  - OBJECTIVE: To study prospectively the values of basal and dynamic measurement of
      inhibin B (INHB), estrodiol (E(2)) following gonadotrophin therapy in vitro
      fertilization (IVF) cycles in predicting ovarian response to stimulation in young
      women. METHODS: A total of 57 patients younger than 40 years of age undergoing
      their first cycle of long protocol IVF treatment were studied and serum INHB,
      E(2) levels were detected on day 3 of the menstrual cycle, before the first
      administration of gonadotrophin (day 0), on days 1 and 5 after gonadotrophin
      therapy (day 1, day 5). Ovarian response was presented by: number of
      oocytes/total rFSH dose and square root of (number of follicles/total rFSH dose).
      According to number of follicles, number of oocytes and presence or absence of
      ovarian hyperstimulation syndrome (OHSS), we categorized the results into three
      different groups: poor response, normal response and OHSS. RESULTS: (1) Hormone
      levels on days 1, 5 of rFSH stimulation: There were positive correlation between
      INHB (r(S): 0.69 - 0.73), E(2) (r(S): 0.60 - 0.73) and ovarian response (P =
      0.000). (2) INHB, and E(2) levels on day 5 of rFSH stimulation were significantly
      different between poor response, normal response and OHSS groups (P < 0.01), and
      INHB levels were 164.7, 696.2 and 1263.5 ng/L respectively, and estrodiol levels
      were 303.2, 1709.5 and 4261.0 pmol/L respectively. CONCLUSIONS: Serum INHB, and
      E(2) levels shortly obtained after gonadotrophin therapy may offer an accurate
      and early prediction of ovarian response, and INHB response to ovarian
      stimulation may be a more sensitive and earlier index of ovarian response than
      estrodiol. Low serum INHB and E(2) levels may predict poor ovarian response; on
      the other hand, high serum INHB and E(2) levels may predict OHSS.

PMID- 16640862
TI  - [Therapeutic effect of puerarin on rats with pre-eclampsia].
AB  - OBJECTIVE: To study the effect of puerarin on the nitrogen monoxide (NO)
      concentration in rats with pre-eclampsia. METHODS: Thirty SD rats were selected
      and divided into three groups: normal pregnancy group, pre-eclampsia model group
      and puerarin group (10 rats in each group). We used endotoxin to set up the pre
      eclampsia model rats on gestation 14th day and puerarin to treat these rats. The
      24 hour urine protein on gestation 8th, 15th, 19th days were determined, as well
      as the heart rate, blood pressure on gestation 10th, 15th, 19th days. Nitrate
      reductase method was used to determine the plasma NO concentration of each group
      on gestation 21st day. RESULTS: (1) There was significant difference in urine
      protein concentration between the puerarin [(73 +/- 20) microg], pre-eclampsia
      [(464 +/- 57) microg], and normal pregnancy [(140 +/- 12) microg], groups (which
      is equal to the value of urine protein of pregnancy 19th day subtracting that of
      pregnancy 8th day, P < 0.01). (2) There was significant difference in blood
      pressure (which is equal to the value of blood pressure of pregnancy 19th day
      subtracting that of pregnancy 10th day) between the three groups (P < 0.01). (3)
      There was no significant difference in changes of heart rate between the three
      groups (which is equal to the value of heart rate of pregnancy 19th day
      subtracting that of pregnancy 10th day, P > 0.05). (4) There was significant
      difference in NO concentration (NO concentration at gestation 19th day
      subtracting that of 8th day) between the three groups (P < 0.01), and the value
      of normal pregnancy group was (158 +/- 31) mmol/L, pre-eclampsia model group (49
      +/- 36) mmol/L, puerarin group (162 +/- 14) mmol/L. CONCLUSION: Puerarin can
      elevate the level of NO concentration and decrease the blood pressure and urine
      protein, but not the heart rate in pre-eclampsia model rats, which suggests that
      puerarin may be used to treat pre-eclampsia.

PMID- 16640863
TI  - [Study of bcl-2 antisense oligodeoxynucleotides on reversal of cisplatin
      resistance in ovarian cancer cell line A2780/DDP].
AB  - OBJECTIVE: To evaluate the influence of bcl-2 antisense oligodeoxynucleotides
      (AODN) on reversing cisplatin (DDP) resistance in ovarian carcinoma cell lines.
      METHODS: In the experiment groups, cisplatin resistant ovarian carcinoma cell
      line A2780/DDP cells were treated with cisplatin after oligodeoxynucleotides were
      transfected by lipofectamine. Cell proliferation was determined by counting the
      number of the cells continuously for six days. The expression level of bcl-2 mRNA
      was detected with reverse transcription polymerase chain reaction (RT-PCR) and
      protein was tested by immunofluorescence technique. The apoptosis of ovarian
      cancer cell lines was measured by DNA ladder assay. The inhibitory rate of cells
      was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      (MTT). The cells treated with culture media were used as the negative control,
      and the untreated cells were used as the blank. RESULTS: The proliferation of
      AODN transfected cells was inhibited significantly compared with that in the
      control groups, and the logarithmic growth delayed for 24h. The expression of bcl
      2 mRNA and bcl-2 protein in AODN transfected cells was 0.76 +/- 0.01 and 171.3 +/
      3.1 respectively. Compared with the expression of bcl-2 mRNA 1.56 +/- 0.03 and
      bcl-2 protein 105.3 +/- 1.7 in the blank, the difference was significant (P <
      0.01), but compared with the same concentration of sense oligodeoxynucleotides
      (SODN) or random-oligodeoxynucleotides (RODN) transfected cells, the difference
      was not significant (P > 0.05). The AODN transfected cells were sensitive to DDP
      again, and the inhibitory rate was (97.49 +/- 1.00)%, which was higher than that
      of the negative control (P < 0.01). In the cells treated with 16 microg/ml AODN
      for 72 h followed by DDP, DNA ladder was obviously observed with agarose gel
      electrophoresis, but in the RODN and SODN transfected cells, DNA ladder could not
      be seen. CONCLUSION: Through inhibiting the expression of bcl-2 mRNA and protein
      and increasing the apoptosis, AODN can reverse the resistance to cisplatin in
      ovarian cancer cell line A2780/DDP.

PMID- 16640874
TI  - [Studies on the relationship between unexplained recurrent spontaneous abortion
      and immunotolerance at the maternal-fetal interface].

PMID- 16640875
TI  - [Two different genetic analyses of spontaneously aborted specimen].
AB  - OBJECTIVE: To explore the feasibility of comparative genomic hybridization (CGH)
      to be used for analysis of spontaneously aborted tissue. METHODS: Thirty eight
      patients with spontaneous abortion were recruited in this study. The gestational
      age of these cases was between 49 and 91 days based on ultrasound scan. All
      specimens of chorionic villi were collected via the cervix. Conventional
      cytogenetic karyotyping and CGH analysis were carried out to detect chromosomal
      unbalanced abnormalities in the tissue specimens. RESULTS: CGH analysis was
      successful in all 38 cases, but cytogenetic karyotying failed in 7 cases.
      Identical results in both CGH and conventional cytogenetic analysis were obtained
      in 90% (28/31) cases. Discrepancy in result between cytogenetic and CGH results
      was shown in 3 cases. One case presented 46XY karyotype by karyotyping, whereas
      showed chromosome 3q(22)-q(24) aberration in CGH analysis. Two cases showed
      triploidy by karyotyping, but normal in CGH analysis. In the 7 cases that failed
      in cytogenetic analysis there were 3 cases showing aneuploidy in CGH analysis.
      CONCLUSION: CGH analysis is feasible to be used for identification of chromosomal
      unbalanced abnormalities related to spontaneous abortion.

PMID- 16640876
TI  - [Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous
      abortion].
AB  - OBJECTIVE: To investigate the relationship between the recurrent spontaneous
      abortion and soluble human leukocyte antigen (HLA) DQB1 gene polymorphism.
      METHODS: Sixty one cases with recurrent spontaneous abortion were included in
      study group. Of them, 31 were anticardiolipin antibody (ACA) positive, while 30
      were negative. Twenty eight cases were with early abortion, 22 were with late
      abortion, and 11 were with both early and late abortions. Thirty six women
      without abnormal pregnancy history were recruited as control group. HLA-DQB1
      genotyping was carried out by polymerase chain reaction-restrictive fragment
      length polymorphism (PCR-RFLP). RESULTS: The frequency of DQB1*0201allele in the
      study group (16.4%, 20/122) was higher than that in the control group (8.3%,
      6/72), but the difference was not statistically significant (P > 0.05). The
      frequency of 57 site with non Asp in the study group was significantly higher
      than that in the control group (P < 0.05). The frequencies of both DQB1*0201 and
      *0303 were significantly different among early abortion, late abortion and both
      early and late abortion groups (P < 0.05 and P < 0.05). The frequency of
      DQB1*0201 was significantly higher in the early abortion group than that in the
      late abortion group (P < 0.01). The frequency of DQB1*0303 was significantly
      increased in the late abortion group when compared to that in the early group (P
      < 0.01). The frequency of DQB1*0303 was found to be significantly higher in
      patients with ACA positive than that in ACA negative group (P < 0.05).
      CONCLUSION: The 57 site with non Asp may be a gene related to recurrent
      spontaneous abortions. DQB1*0201 may be correlated to the early abortion, while
      DQB1*0303 correlated to the late abortion and abortion with ACA positive.

PMID- 16640877
TI  - [A/G polymorphism at position 49 in exon 1 of CTLA-4 gene in Chinese women with
      unexplained recurrent spontaneous abortion].
AB  - OBJECTIVE: To investigate whether A/G polymorphism at position 49 in exon 1 of
      cytotoxic T lymphocyte antigen-4 (CTLA-4) gene confers the susceptibility to
      unexplained recurrent spontaneous abortion in Chinese population. METHODS: One
      hundred and sixty-eight restrictive Chinese women with unexplained recurrent
      spontaneous abortion (URSA) and 117 women with normal pregnancy as control were
      included in this study. Polymerase chain reaction restrictive fragment length
      polymorphism (PCR-RFLP) was used to detect the polymorphism at position 49 in
      exon 1 of CTLA-4 gene. The frequency of alleles G/A, genotypes AA/AG/GG and
      phenotypes A+ (AA + AG)/G+ (GG + AG) of CTLA-4 were compared between URSA
      patients and controls. RESULTS: The different distributions of alleles G/A,
      genotype AA/AG/GG and phenotypes A+/G+ of CTLA-4 were observed between URSA
      patients and controls. The frequencies of both G allele [68.4% (230/336) vs 59.4%
      (139/234), P < 0.05] and GG genotype [48.8% (82/168) vs 33.3% (39/117), P < 0.05]
      were significantly higher in URSA group than that in control group, while the
      frequencies of AG genotype [39.3% (66/168) vs 52.1% (61/117), P < 0.05] and A+
      (AA + AG) phenotype [51.2% (86/168) vs 66.7% (78/117), P < 0.05] were
      significantly lower in URSA group than that in control group. CONCLUSIONS: The
      results suggest that A/G polymorphism in exon-1 of CTLA-4 might confer the
      susceptibility to RSA in Chinese women.

PMID- 16640878
TI  - [Expression of leukemia inhibitory factor in chorionic villi of normal early
      pregnancy, threatened abortion and inevitable abortion].
AB  - OBJECTIVE: To examine the expression of leukemia inhibitory factor (LIF) in
      chorionic villi of normal early pregnancy, threatened abortion and inevitable
      abortion, and to assess the effects of LIF on threatened abortion and inevitable
      abortion. METHODS: Expression of LIF in chorionic villi was examined using
      Western blot. Serum progesterone and human chorionic gonadotropin (hCG) levels
      were determined using radioimmunoassay. A streptavidin peroxidase conjugated semi
      quantitative immunohistochemical assay was used to exam LIF protein expression.
      RESULTS: The levels of progesterone and hCG in the normal early pregnancy and
      threatened abortion groups were (95 +/- 26) nmol/L and (75 +/- 14) kU/L, and (90
      +/- 26) nmol/L and (68 +/- 13) kU/L, respectively. The differences were not
      significant (P > 0.05). The levels of progesterone and hCG in the inevitable
      group were significantly decreased to (36 +/- 17) nmol/L and (13 +/- 3) kU/L,
      respectively. The differences when compared to the other groups were
      statistically significant (P < 0.01). LIF protein expression was observed in all
      cases and located mainly in the cytoplasm of trophoblast cells. The expression of
      LIF in inevitable abortion group 0.30 +/- 0.02 was lower than that in other
      groups (P < 0.01). However, there was no significant difference in the expression
      of LIF between the normal early pregnancy group and threatened abortion group (P
      > 0.05). CONCLUSION: LIF may play a role in the maintenance of normal pregnancy.
      Reduction of LIF expression in chorionic villi may induce the decrease of serum
      progesterone and hCG levels and, ultimately, cause inevitable abortion.

PMID- 16640879
TI  - [Effects of general anesthesia for cesarean section on infants].
AB  - OBJECTIVE: To determine the safety of general anesthesia during cesarean section
      for neonates. METHODS: Singleton pregnant women for whom elective cesarean
      sections were planned after 37 gestation weeks were allocated to general
      anesthesia or epidural anesthesia. After preoxygenation, general anesthesia was
      induced with fentanyl (2.0 microg/kg), propofol (1.5 mg/kg) and vencuronium (0.08
      mg/kg) followed by tracheal intubation. Oxygen-nitrous oxides (50%) was inhaled
      before delivery. Epidural anesthesia was performed at L(1 - 2) or L(2 - 3) on the
      left lateral decubitus position with 1.73% lidocaine carbonate (including 1:200
      000 adrenaline). We studied arterial samples withdrawn from the infants 30 min
      after birth for the pH, PaO(2), PaCO(2), SPO(2) and Hct. Neonatal behavioral
      neurological assessments (NBNA) 3 - 5 days after birth were recorded. RESULTS:
      (1) The pH, PaO(2), PaCO(2), SPO(2) and Hct in the general anesthesia group were
      7.34 +/- 0.08, (40 +/- 11) mm Hg, (73 +/- 17) mm Hg, (96.8 +/- 1.0)%, and (53 +/-
      5)%, while in the epidural anesthesia group were 7.35 +/- 0.05, (41 +/- 8) mm Hg,
      (71 +/- 17) mm Hg, (96.6 +/- 1.0)%, and (54 +/- 6)%. (2) NBNA scores: In the
      general anesthesia group, neonatal adaptive capacity, passive tone, active tone,
      primary reflexes and general status were 12.6 +/- 0.7, 7.2 +/- 0.7, 7.4 +/- 0.6,
      5.6 +/- 0.8, and 5.9 +/- 0.3 respectively. While in the epidural anesthesia group
      they were 13.4 +/- 0.8, 7.3 +/- 0.5, 7.3 +/- 0.8, 5.6 +/- 0.6, and 5.9 +/- 0.3
      respectively. No significant difference was seen (P > 0.05) between the general
      anesthesia group and the epidural anesthesia group in NBNA scores, mean pH,
      PaO(2), PaCO(2), SPO(2) and Hct of newborn infants. CONCLUSION: It study suggests
      that general anesthesia for the elective cesarean section does not influence
      significantly the outcome of the newborn infants.

PMID- 16640880
TI  - [Hepatitis B immunoglobulins blocking hepatitis B virus infection of trophoblast
      cell culture in vitro].
AB  - OBJECTIVE: To determine the role of hepatitis B Immunoglobulins (HBIG) in
      blocking hepatitis B virus (HBV) infection of trophoblast cell culture in vitro.
      METHODS: Trophoblast cells were placed in the six-well cluster dishes and
      incubated with 10% fetal calf serum/Dubecco's modified Eagle's Medium (10% FCS
      DMEM) at 37 degrees C with 5% CO2 in air. At 24 h after plating cells were
      subjected to experiment. Group A: cells were cultured with 0.5 ml HBV positive
      serum plus 3 ml 2% FCS DMEM; Group B: cells were cultured with 3 ml 2% FCS DMEM
      plus 0.5 ml HBV positive serum pretreated with 80 U HBIG for 30 min at 37 degrees
      C; Group C: cells were cultured with 3 ml 2% FCS DMEM plus 0.5 ml HBV positive
      serum pretreated with 40 U HBIG for 30 min at 37 degrees C; Group D: cells were
      cultured with 3 ml 2% FCS DMEM plus 40 U HBIG for 30 min before 0.5 ml HBV
      positive serum was added; Group E: cells were cultured with 40 U HBIG plus 3 ml
      2% FCS DMEM; Group F: cells were cultured with HBV negative serum plus 3 ml 2%
      FCS DMEM. Twenty-four hours later the inoculums were removed, and the cells were
      extensively washed with 0.01 mol/L phosphate-buffered saline (PBS). After PBS
      washing, 4 ml 2% FCS DMEM was added to each well and the medium was collected
      every 12 hours. Enzyme-Linked Immunosorbent Assay (ELISA) method was used to
      detect HBsAg in culture medium (absorption value, A). HBV DNA in cell culture
      medium was detected by polymerase chain reaction (PCR). RESULTS: Before PBS
      washing, the A value of groups A, B, C, D, E, F were 2.697, 0.040, 0.102, 0.198,
      0.036, 0.040 respectively. The cell culture medium in groups of A, B, C, and D
      were HBV DNA positive, groups of E, F were HBV DNA negative. From 12 hours to 84
      hours, the average A value of groups A, B, C, D, E and F was 1.55 +/- 0.27, 0.032
      +/- 0.016, 0.100 +/- 0.087, 0.052 +/- 0.044, 0.034 +/- 0.020, 0.034 +/- 0.022
      respectively. The A value of groups A was significantly higher than those of
      other groups (P < 0.01). Cell culture medium at 84 hours of group A was HBV DNA
      positive and those of group B, C, D, E, F were HBV DNA negative. CONCLUSION: HBIG
      could effectively block HBV infection of trophoblast cell culture in vitro.

PMID- 16640882
TI  - [Relationship of phenotype with type of deletion of dystrophin gene].
AB  - OBJECTIVE: To detect the distribution characteristics of dystrophin gene
      deletions in the northeastern of China and the relationship of severity with type
      of deletion. METHODS: To screen deletion distribution of 124 DMD/BMD patients via
      multiplex PCR, male high-risk fetuses were detected deletion by the same method.
      RESULTS: The deletion frequency was 49%. Deletions located in the regions of
      exons 45 - 53 and exons 8 - 19 were 41 (67%) and 13 (21%) cases respectively, and
      in 5 (8%) cases deletions were scattered over both regions, still 2 cases (3%)
      were checked up deletions lying in exons 34 and 43; there were 9 cases of in
      frame deletions and 49 frameshift mutations in all deletions; of 30 high-risk
      fetuses 10 male ones were screened deletions, who had the same deletion-segments
      as their probands. CONCLUSIONS: The distribution of dystrophin gene deletions in
      the northeastern of China cluster mainly in two hot-spots, neighboring regions of
      exon 8 might be a real deletion "hot spot" in this region; the phenotype is
      associated with the type of gene deletion, the phenotype is BMD when in-frame
      deletions occur; severe DMD when frameshift mutations occur. Multiplex PCR method
      provides the short-cuts for detecting patients and making prenatal gene
      diagnosis.

PMID- 16640883
TI  - [In vitro maturation and fertilization of unstimulated immature oocyte for the
      treatment of infertile women].
AB  - OBJECTIVE: To evaluate the efficacy of in vitro maturation (IVM) and
      fertilization of unstimulated immature oocytes for the treatment of infertile
      women. METHODS: Fifty-four cycles of IVM were carried out in 40 patients
      including 26 women with infertility due to polycystic ovary syndrome (PCOS), and
      14 patients with history of assisted reproductive technology (ART) failure.
      Transvaginal ultrasound-guided oocyte collection was performed during menstrual
      cycle days 9 - 12 without pretreatment of gonadotropins. After 24 - 48 hours of
      culture, the metaphase II stage oocytes were inseminated by intracytoplasmic
      sperm injection (ICSI). Embryo transfer was performed 2 or 3 days after ICSI.
      Laser assisted hatching was done before embryo transfer. RESULTS: Seven cycles
      were cancelled and the cancel rate was 13% (7/54). A total of 857 immature
      oocytes were obtained with the mean numbers of 18.2 per cycle, and 632 oocytes
      developed at MII stage (73.7%, 632/857). A total of 476 oocytes were fertilized
      by ICSI (75.3%, 476/632), with a cleavage rate of 91.2% (434/476). Embryo
      transfer was performed in 47 cycles and the mean number of embryos transferred
      were 4.3 per cycle (range: 2 - 6). The mean endometrial thickness on the day of
      embryo transfer was 8.9 mm. Nineteen clinical pregnancies were obtained, giving a
      pregnancy rate of 35% (19/54) per start cycle and 40% (19/47) per transfer cycle.
      CONCLUSIONS: IVM of unstimulated immature oocytes for the treatment of women with
      various causes of infertility especially due to PCOS is an effective alternative
      method. The clinical pregnancy rate of 40% (19/47) is similar to that by
      conventional in vitro fertilization treatment in our unit.

PMID- 16640884
TI  - [Clinical characteristics and genetic analyses of familial recurrent moles].
AB  - OBJECTIVE: To probe the clinical characteristics and genetic origin of familial
      recurrent mole (FRM). METHODS: Two cases of FRM were reported retrospectively.
      Microsatellite polymorphism was used to determine the genetic origin of the two
      FRM and other six sporadic moles from other independent families. RESULTS: The
      two FRM patients came from two independent families. Both of them had more than
      two times of hydatidiform moles and the same condition had happened to their
      sisters. The last mole from each of these two patients was identified as
      biparental complete hydatidiform mole (BiCHM). Among the six sporadic moles, one
      was partial hydatidiform mole (PHM), which was identified as triploid with one
      haploid maternal set of chromosomes and two haploid paternal sets of chromosomes.
      The other five sporadic moles were all androgenetic complete hydatidiform mole
      (AnCHM), which lacked maternal genetic material. The two women with FRM developed
      into persistent trophoblastic disease (PTD) and gained complete remission (CR)
      after medical therapy and/or pulmonary lobectomy. CONCLUSIONS: FRM is exceedingly
      rare. Most of them are biparental in origin. It ought to be an important step to
      identify the genetic origin in evaluating the outcomes of the women with
      recurrent hydatidiform moles.

PMID- 16640885
TI  - [Oocyte activation with calcium ionophore A23187 and puromycin on human oocytes
      that fail to fertilize after intracytoplasmic sperm injection].
AB  - OBJECTIVE: To investigate the effect of assisted oocyte activation with calcium
      ionophore A23187 and puromycin on human oocytes that fail to fertilize after
      intracytoplasmic sperm injection (ICSI). METHODS: All 113 discarded oocytes that
      showed no evidence of fertilization at 16 - 18 hours after in vitro maturation
      (IVM)-ICSI cycles and conventional ICSI were assigned to four groups according to
      the time after ICSI: IVM-ICSI 22-hour group (n = 33), IVM-ICSI 44-hour group (n =
      18), ICSI 44-hour group (n = 37) and ICSI 68-hour group (n = 25). All
      unfertilized oocytes were exposed to calcium ionophore A23187 (5 micromol/L) for
      5 minutes and subsequently incubated with puromycin (10 microg/ml) for 4 hours.
      After incubation, the oocytes were cultured in vitro for 3 - 5 days. The
      activation rate, proportion of oocytes that showed pronucleus formation and
      cleavage rate were calculated after activation. Sex chromosomal analysis was
      performed by dual color fluorescence in situ hybridization (FISH) on the embryos
      that displayed two pronuclei and a second polar body. RESULTS: The combination of
      calcium ionophore A23187 with puromycin could activate the unfertilized oocytes
      22 - 68 hours after ICSI. Best results were achieved in IVM-ICSI 22-hour group,
      which elicited 88% (29/33) of activation rate, 62% (18/29) of cleavage rate and
      28% (5/18) of 4-cell embryos. One embryo in this group developed to the morular
      stage. The activation rate and developmental potential of the activated embryos
      in IVM-ICSI 44-hour group, ICSI 44-hour group and ICSI 68-hour group decreased.
      FISH analysis showed 4 embryos with XX and 9 embryos with XY in 16 embryos.
      CONCLUSIONS: The combination of calcium ionophore A23187 with puromycin could
      effectively activate unfertilized oocytes 22 - 68 hours after ICSI. The cultured
      time of unfertilized oocytes after ICSI affects activation efficiency and
      developmental potential of the activated embryos. The activated zygotes that
      display two pronuclei and a second polar body can develop normally.

PMID- 16640886
TI  - [Growth inhibitory effects of lipofectamine-mediated DCC gene on ovarian
      epithelial carcinoma].
AB  - OBJECTIVE: To study the inhibitory effects of lipofectamine-mediated deleted
      colorectal carcinoma gene on ovarian epithelial carcinoma (ovarian cancer) cell
      line SKOV3. METHODS: We constructed a recombinant eukaryotic expression vector
      pcDNA3.1 (+)-DCC containing exogenous human DCC cDNA and vector with neomycin
      resistance gene, which were introduced by lipofectamine-mediated gene
      transfection into SKOV3 cell line that does not express DCC endogenously, thus
      forming SKOV3/DCC. Therefore, the experimental cells were classified into
      SKOV3/DCC, SKOV3/Neo and SKOV3. By using reverse transcriptase-polymerase chain
      reaction and immunocytochemistry, the expression of DCC mRNA and its protein were
      examined. RESULTS: Exogenous DCC had successfully been transferred into SKOV3
      cells and obtained permanent expression. The growth speed of SKOV3/DCC was slower
      than the other two groups, there was significant difference between them (P <
      0.01). SKOV3/DCC clones number was 38 +/- 8, while SKOV3 and SKOV3/Neo were 192
      +/- 8 and 186 +/- 10, respectively, there was significant difference between them
      (P < 0.01). The percentage of G(1) phase cells increased to 78.0%, which that of
      S phase decreased to 5.3% by analyzing cell cycle, there was significant
      difference between them (20.0% and 3.2%, P < 0.01). The ultrastructural changes
      of the cells were observed under electron microscope, revealing growth
      retardation. CONCLUSION: DCC gene played an important role in generation and
      development of ovarian carcinomas.

PMID- 16640887
TI  - [Effect of small interference RNA on E6, E7 mRNA of human papillomavirus type-18
      in cervical cancer cells].
AB  - OBJECTIVE: To study the effect of small interference RNA on E6, E7 mRNA of human
      papillomavirus type-18 (HPV18) in cervical cancer cells. METHODS: The specific
      HPV18E6 and E7 siRNA synthesized by in virtro transcription. The cell activity
      was detected by methyl thiazolyl tetrazolium (MTT) assay to determine the most
      suitable concentration, then cells were transfected into HPV18 cervical cancer
      cells by oligofectamine. HPV18E6, E7 mRNA level was examined by semi-quantitative
      RT-PCR, and the cell cycles were analyzed by flow cytometry. RESULTS: The
      activity of the HeLa cells had an obvious suppression after transfection to 0.57
      +/- 0.05 and 0.62 +/- 0.04 compared with the contrast of 0.87 +/- 0.05. The
      expression of HPV18E6 mRNA level was 0.63 +/- 0.04 before transfection, decreased
      to 0.53 +/- 0.04, 0.46 +/- 0.02, 0.56 +/- 0.03 evidently after transfection at
      24, 48, 72 hours. The expression of HPV18E7 mRNA level was 0.66 +/- 0.03 before
      transfection and decreased to 0.60 +/- 0.05, 0.52 +/- 0.04, 0.59 +/- 0.02 after
      transfection at 24, 48, 72 hours. The number of cells in G(2) phase was increased
      after HPV18E6 siRNA transfection from (1.4 +/- 1.2)% to (66.9 +/- 3.5)%, S phase
      was declined from (39.4 +/- 0.4)% to (0 +/- 5.5)%, and they were (47.2 +/- 0.5)%
      and (5.6 +/- 4.2)% in E7 group. CONCLUSION: RNAi exists in HeLa cells, and its
      effect has specificity.

PMID- 16640888
TI  - [Interactions of ovarian carcinoma cells and human peritoneal mesothelial cells
      involved in matrix metalloproteinases expressions of ovarian carcinoma cells].
AB  - OBJECTIVE: To investigate the interactions of ovarian carcinoma cells and human
      peritoneal mesothelial cells (HPMC) involved in matrix metalloproteinases (MMP)
      expressions of ovarian carcinoma cells. METHODS: The conditioned medium (CM) of
      ovarian carcinoma cell SKOV3 was tested by enzyme-linked immunosorbent assay
      (ELISA) for transforming growth factor beta1 (TGF-beta1). The impact of SKOV3-CM
      in the presence or absence of TGF-beta1 neutralizing antibody on fibronectin (Fn)
      gene expression of HPMC was studied by RT-PCR. HPMC were pretreated with serum
      free medium, SKOV3-CM, SKOV3-CM + TGF-beta1 neutralizing antibody, and SKOV3-CM +
      IgG, then the supernatant was collected as HPMC-CM(1), HPMC-CM(2), HPMC-CM(3) and
      HPMC-CM(4). SKOV3 were incubated with different HPMC-CM, HPMC-CM(1) + antibody
      against Fn or HPMC-CM(1) + IgG. MMP-2 and MMP-9 gene mRNA expressions and protein
      expressions of SKOV3 were detected by RT-PCR and ELISA respectively. RESULTS: TGF
      beta1 in SKOV3-CM was (236 +/- 22) ng/L. Fn gene mRNA expressions of HPMC before
      and after stimulation by SKOV3-CM were 1.328 +/- 0.025 and 2.643 +/- 0.051, and
      the latter was higher than the former (P < 0.05). Fn gene mRNA expressions of
      HPMC stimulated by SKOV3-CM + TGF-beta1 neutralizing antibody was 1.897 +/-
      0.035, which was less than that of SKOV3-CM group (P < 0.01). Before SKOV3 were
      incubated with HPMC-CM, MMP-9 protein and mRNA expressions were (14.5 +/- 1.6)
      microg/L and 1.50 +/- 0.04, but protein and mRNA expressions of MMP-2 were
      scarcely detected. When SKOV3 were incubated with HPMC-CM(1), mRNA expressions of
      MMP-2 and MMP-9 were 0.226 +/- 0.012 and 2.66 +/- 0.07, protein expressions were
      (15.0 +/- 0.8) and (37.2 +/- 3.5) microg/L, which were all higher than those of
      SKOV3 without treatment of HPMC-CM (P < 0.01). Following incubation of SKOV3 with
      HPMC-CM(1) + antibody against Fn, mRNA expressions of MMP-2 and MMP-9 were 0.138
      +/- 0.007 and 1.82 +/- 0.06, protein expressions were (8.8 +/- 0.7) and (25.8 +/-
      2.5) microg/L, which decreased compared with those of HPMC-CM(1) group (P <
      0.01). Following incubation of SKOV3 with HPMC-CM(2), mRNA expressions of MMP-2
      and MMP-9 were 0.467 +/- 0.018 and 4.28 +/- 0.09, protein expressions were (39.3
      +/- 3.6) and (62.0 +/- 5.3) microg/L, which were higher than those of HPMC-CM(1)
      group (P < 0.01). Following incubation of SKOV3 with HPMC-CM(3), gene expressions
      of MMP-2 and MMP-9 were 0.331 +/- 0.015 and 3.52 +/- 0.08, protein expressions
      were (27.6 +/- 1.9) and (50.0 +/- 4.1) microg/L, which decreased compared with
      HPMC-CM(2) group (P < 0.05), but were still higher than those of HPMC-CM(1) group
      (P < 0.05). CONCLUSIONS: Ovarian carcinoma cells activate HPMC through TGF-beta1,
      which induces higher expressions of MMP of ovarian carcinoma cells. Up-regulating
      Fn expression of HPMC may be one of action mechanisms of ovarian tumor cells. Fn
      derived from HPMC stimulates MMP-2 and MMP-9 expressions of ovarian carcinoma
      cells at gene and protein levels.

PMID- 16640898
TI  - [Relationship between the absorption of dietary calcium and the Fok I
      polymorphism of VDR gene in young women].
AB  - OBJECTIVE: To investigate the relationship between the absorption of dietary
      calcium and VDR (Vitamin D(3) receptor, VDR) gene RFLPs in Chinese young women
      with representative diets. METHODS: Forty subjects were selected from three
      hundred young female students aged 18 - 23 years old. After identifying the VDR
      gene Fok I RFLPs, the subjects were given the representative diets during the 3
      day adaptation period and the 12-day metabolism period. The copy food and
      drinking for measurement of nutrients and also the complete feces each day were
      collected. The dietary calcium absorption of each subject was examined and
      calculated. RESULTS: As expected, the intake of dietary calcium in subjects is
      close to the results set by the of National Nutrition Investigation in 1992 (from
      young women at 17 year old) or the daily reference intake (DRI) for adult woman;
      the difference of the absorption of dietary calcium among VDR gene RFLPs in young
      women was observed: ff < Ff < FF, (28.7 +/- 10.5)%, (30.4 +/- 15.9)% and (40.6 +/
      11.0)% respectively; only significant difference between FF genotype and Ff
      genotype, P < 0.05. CONCLUSION: Our results were consistent with those gained
      from the previous studies on children about the relationship between the
      absorption of dietary calcium and VDR (Vitamin D(3) receptor, VDR) gene RFLPs,
      and now it might occur in young women. Further studies need to be taken by using
      stable isotope and increasing subjects in young women.

PMID- 16640900
TI  - [Vitamin C reverses benzo (a) pyrene-induced cell cycle changes by E2F pathway].
AB  - OBJECTIVE: To study the role of E2F1/4 pathway in vitamin C reversing benzo (a)
      pyrene [B (a) P]-induced changes of cell cycle in human embryo lung fibroblasts
      (HELF) and the relationship between E2F1 and cyclin D1/CDK4. METHODS: The stable
      transfectants, HELF transfected with antisense cyclin D1 and antisense CDK4, were
      established to detect the relationship of signaling pathway. Cells were cultured
      and pretreated with vitamin C before stimulation with B (a) P for 24 hours. The
      expression levels of cyclin D1, CDK4, E2F1 and E2F4 were determined by Western
      blot and the band intensity was analysed as the relative value to control by
      using the Gel-Pro 3.0 software. Flow Cytometric Analysis was employed to detect
      the distributions of cell cycle. RESULTS: B (a) P significantly elevated the
      expression levels of cyclin D1, CDK4, E2F1 and E2F4 in HELF cells. Vitamin C
      decreased the expression levels of above proteins in B (a) P-stimulated HELF
      cells. The expression levels of these proteins in B (a) P-treated above
      transfectants were lower than those in B (a) P-treated HELF cells. The expression
      levels of above proteins with vitamin C combined with antisense cyclin D1 were
      decreased as compared to those with antisense cyclin D1 alone. B (a) P increased
      the percentage of S phase as compared to the controls [(41.1 +/- 0.2)% vs (33.5
      +/- 3.2)%, P < 0.05]. Both vitamin C [(33.2 +/- 0.6)% vs (41.1 +/- 0.2)%, P <
      0.05] and antisense cyclin D1 [(31.2 +/- 1.3)% vs (41.1 +/- 0.2)%, P < 0.05]
      suppressed the changes of cell cycle induced by B (a) P. Vitamin C combined with
      antisense CDK4 markedly suppressed B (a) P-induced changes of cell cycle as
      compared to those with antisense CDK4 alone. CONCLUSION: Vitamin C might reserve
      the B (a) P-induced changes of cell cycle via intracellular signaling pathway of
      cyclin D1-CDK4/E2F-1/4.

PMID- 16640902
TI  - [Expression deficiency of JWA enhanced DNA damage and delayed DNA repair in HeLa
      cells induced by benzo (a) pyrene exposure].
AB  - OBJECTIVE: To investigate the role of JWA gene in benzo (a) pyrene [B (a) P]
      induced DNA damage and repair effects in HeLa cells. METHODS: The antisense JWA
      express vector (pEGFP-C1-asJWA) was constructed and stably transfected into HeLa
      cells. JWA deficient HeLa cells (asJWA-HeLa) was then screened and established.
      The general characteristics of asJWA-HeLa cells were investigated. DNA damage and
      repair cell culture model was conducted by treating the cells with 50 micromol/L
      B (a) P plus S9 for 3 hours and then the cells were maintained further 0, 1, 3,
      and 24 hours for DNA repairing. The damaged DNA was detected by single cell gel
      electrophoresis assay (comet assay). RESULTS: JWA deficient HeLa cells (with a
      31% of JWA protein expression as compared with the control) were obtained
      successfully. Compared with the empty vector transfected cells (C1-HeLa) and the
      untransfected HeLa cells, asJWA-HeLa cells were more sensitive to B (a) P
      exposure and with a delayed DNA repair process. CONCLUSION: The JWA determined
      might function as a potential effective environmental responsive gene and
      actively participate the process of B (a) P exposure associated with
      intracellular signal pathways of DNA damage and repair.

PMID- 16640903
TI  - [Study on the level of environmental endocrine disruptors in serum of precocious
      puberty patients].
AB  - OBJECTIVE: To investigate the role of environmental endocrine disruptors (EEDs)
      in causing the precocious puberty. METHODS: The blood samples were collected from
      79 cases of precocious puberty patients and 42 cases of normal children. The
      concentrations of 4-nonylphenol (4-NP), 1, 1-dichloro-2, 2, bis (p-chlorophenyl)
      ethylene (p, p'-DDE) and di-2-ethylhexyl phthalate (DEHP) in blood serum samples
      were measured by using reversed-phase high performance liquid chromatography
      (HPLC). The volume of uterus and ovary, the bone density, and the content of
      estradiol (E(2)) in serum were determined at the same time. The contents of EEDs
      in blood serums of precocious puberty and the indices of the target organs were
      analyzed by using of correlation and regression. RESULTS: In normal control
      group, p, p'-DDE was detected in all the blood samples (14.93 - 40.39 ng/ml), but
      4-NP and DEHP were detected in some samples (ND -6.77 ng/ml, ND -17.61 ng/ml).
      The levels of 4-NP, p, p'-DDE and DEHP in blood serum in precocious puberty group
      were notably increased than that in control group (P < 0.01). In precocious
      puberty group, there was a positive correlations between the 4-NP in volume of
      uterus and the volume of ovary and the density of bone (r = 0.394, 0.286, 0.237,
      P < 0.01); p, p'-DDE and volume of uterus also showed a the positive correlation
      (r = 0.306, P < 0.01). The influencing extent of 4-NP was 1.3 times to that of
      the p, p'-DDE. CONCLUSION: The normal children and the children with precocious
      puberty should be all contaminated by EEDs, and the later be exposured to more
      EEDs. There might exist a close relationship between EEDs and the precocious
      puberty, and EEDs should be an important factor in causing the disease. Different
      kinds of EEDs might have different influencing extents to the target organs.

PMID- 16640904
TI  - [Measurement of personal noise exposure in a cold rolling mill].
AB  - OBJECTIVE: To measure and evaluate the personal noise exposure of cold rolling
      mill workers by using noise dosimeter. METHODS: According to job category and
      work type, all workers were divided into 11 groups. 3 to 5 day shift (8:00 to
      16:00) workers from each group were selected as subjects for personal noise
      exposure measurement. SH-126 dosimeters were worn by each subject and collect
      noise data by a phone fix at collar. All subjects were asked to take notes about
      their working activities when they were wearing SH-126 dosimeters. Each worker's
      L(A)(eq) of 8 hours, geometric mean and range of each group were computed.
      RESULTS: There were many noise sources in the workshop. Recorded data showed that
      noise exposure of cold rolling mill was unstable. The varieties of personal noise
      levels were quite large. Among 53 workers, the highest noise exposure level was
      100.0 dB (A), the lowest was 81.2 dB (A); the highest work type was of the
      foreside welders [94.20 dB (A)], and the lowest was of the straight-cutters
      [89.02 dB (A)]; quality checkers had the biggest rang [16.3 dB (A)], and primary
      rolling workers had the lest [2.3 dB (A)]. CONCLUSION: Noise exposure of all the
      11 groups were more than 85 dB (A). Noise protection of these workers should be
      improved. It suggested that measuring personal noise exposure individually with
      dosimeters might obtain the noise exposure level more integrally in the
      complicated environment.

PMID- 16640906
TI  - [Enhancement effect of polychlorinated biphenyl on benzo (a) pyrene-induced DNA
      damage in HepG2 cells].
AB  - OBJECTIVE: To study the effect of polychlorinated biphenyl, Aroclor1254 on benzo
      (a) pyrene [B (a) P]-induced DNA damage in HepG2 cells. METHODS: HepG2 cells were
      pretreated with Aroclor1254 (11.5, 23 and 46 micromol/L) for 24 hours and then
      exposed to B (a) P (50 micromol/L). DMSO (10 ml/L) was used as solvent control.
      Single cell gel electrophoresis (SCGE) and high-performance liquid chromatography
      electrochemical detection (HPLC-EC) assays were applied to detect DNA single
      strand breaks and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in HepG2 cells,
      respectively. RESULTS: Average Oliver tail moment (OTM) and 8-OHdG level in HepG2
      cells were significantly increased in B (a) P treated group (1.66 +/- 0.21),
      (23.31 +/- 6.02) 8-OHdG/10(6)dG than that in solvent control (0.79 +/- 0.15),
      (12.31 +/- 3.24) 8-OHdG/10(6)dG, respectively. In Aroclor 1254 treated group
      (11.5, 23.0, 46.0 micromol/L), average OTM were 0.88 +/- 0.20, 1.01 +/- 0.15 and
      1.10 +/- 0.16, and 8-OHdG levels were (19.57 +/- 7.57), (22.80 +/- 9.16) and
      (31.74 +/- 9.25) 8-OHdG/10(6)dG, respectively. A concentration of 46 micromol/L
      Aroclor1254 caused a significant increase of 8-OHdG level as compared with the
      solvent control. After pretreatment of HepG2 cells with Aroclor1254 (11.5, 23.0
      and 46.0 micromol/L), B (a) P induced more DNA strand breaks (OTM: 2.14 +/- 0.22,
      2.43 +/- 0.32 and 2.71 +/- 0.31) and 8-OHdG [(32.50 +/- 3.81), (49.23 +/- 16.66)
      and (60.36 +/- 18.04) 8-OHdG/10(6)dG] in HepG2 cells than B (a) P alone.
      CONCLUSION: Aroclor1254 might enhance B (a) P-induced DNA damage in HepG2 cells,
      which should imply a synergistic effect of Aroclor1254 on the genotoxicity of B
      (a) P.

PMID- 16640908
TI  - [Effects of lead exposure to rat placenta and pups during different gestation
      periods].
AB  - OBJECTIVE: To investigate the effects of lead exposure to rat placenta and pups
      during different gestation periods. METHODS: All 108 Wistar rats (72 females, 36
      males) were randomly divided into four groups. All rats were orally fed with
      0.025% lead acetate during different gestation periods. Blood was obtained from
      the abdominal vena cava and the lead level in maternal blood was measured by
      means of atomic absorption spectrometry at the end of the pregnancy. The number
      of pups, their body weight, body length and tail length were measured. The
      effects of lead to rat placenta were observed by level of microscopy, optical
      microscopy and electronic microscopy. RESULTS: Experimental groups the blood lead
      level at the end of gestation were above 0.483 micromol/L. There were significant
      differences among, of pups, during different groups (P < 0.01). Among them the
      drinking lead group of whole distant was the lowest in placenta weight [(0.31 +/-
      0.13) g] body weight of pups [(2.08 +/- 0.88) g] length and tail length of pups
      [(2.37 +/- 0.32) cm, (0.98 +/- 0.09) cm]. There were significantly differences
      between the experimental groups and controls. Maternal blood lead level was
      negatively related to placenta weight (r = 0.652, P < 0.01), and had no relation
      with the body weight of pups (r = -0.107, P = 0.46). In the experimental groups
      of lead poisoned rats, the placenta showed focus necrosis in the deciduas, and
      increased the trophoblastic giant cells and light staining cells in the
      trophospongium. Trophoblast in the labyrinth and trophospongium showed
      degeneration; fibrin deposition around the villi was increased. Microvilli around
      the trophoblast were shorter and less, mitochondrion was swollen and decreased in
      number, rough endoplasmic reticulum was distended and ribosomal number on
      membrane decreased. CONCLUSION: Lead exposure during different gestation periods
      should have a traumatic effect on the trophoblast, leading to interference of
      nutrition and oxygen exchange. Furthermore, the blood supply to the placenta and
      nutrition and oxygen exchange between mother and pups were also interfered,
      leading to reduction of placenta weight and retardation of development of pups.

PMID- 16640910
TI  - [Cross-sectional study on growth and development of Chinese Han students].
AB  - OBJECTIVE: To analyze the current situation of the growth and development on
      Chinese Han children and adolescents. METHODS: Using the 2004 National Survey on
      Students' Physical Fitness and Health, the body height, weight and chest
      circumference of 161,477 subjects aged 7 to 18 enrolled in this study were
      analyzed. RESULTS: It showed that the levels of the growth and development in
      urban students were better than those of rural students (P < 0.01). The average
      level on stature of 12-aged students were 152.78 cm and 148.66 cm respectively
      for urban and rural boys, and the deference was 4.12 cm; the mean heights of
      urban and rural girls were 152.68 cm and 149.24 cm respectively, and the
      deference was 3.44 cm. The average level on body weight of 12-aged students were
      44.75 kg and 39.27 kg respectively for urban and rural boys, and the deference
      was 5.48 kg; the mean weights of urban and rural girls were 42.91 kg and 39.17 kg
      respectively, and the deference was 3.74 kg. The average level on chest
      circumference of 12-aged urban students was beyond the rural students 3.68 cm and
      2.56 cm respectively by gender. The average level on body height and weight of 7
      to 14 aged students of east inshore areas were more than those of southwest,
      northwest and middle areas (P < 0.01). The mean body height and weight of
      students of southwest area were the lowest in whole country (P < 0.01).
      CONCLUSION: It reveals that attaching further importance to improve the work of
      students' physical fitness and health and nutrition in inland areas, especially
      in southwest areas and rural areas, would be contributory to the growth and
      development of the children and adolescents.

PMID- 16640911
TI  - [Application of pulse field gel electrophoresis in molecular typing method on
      dealing with the outbreak of intestinal pathogen].
AB  - OBJECTIVE: To explore and establish fast and sensitive typing diagnostic methods
      on intestinal pathogen. METHODS: All 29 isolates of Shigella. sonnei and 12
      strains of Escherichia coli O157:H7 (EHEC O157:H7) isolated in 1999 were carried
      out for typing by using pulse-field gel electrophoresis (PFGE) and phage typing.
      RESULTS: PFGE results of 4 outbreak incidents caused by Shigella. sonnei showed
      that the PFGE patterns of the strains isolated from the same incident were almost
      the same. It was also the same during analysing the 2 outbreak incidents caused
      by EHEC O157:H7, however, the PFGE patterns of the 3 individual strains of EHEC
      O157:H7 were different. Moreover, the phage typing method showed its fine typing
      ability while its being used in the analysing 12 strains of EHEC O157:H7.
      CONCLUSION: The fine typing ability and reliability of PFGE was helpful for
      finding out the heredity background of intestinal pathogen and the infectious
      resource of the outbreak. And the epidemic situation might thus be effectively
      prevented from spreading.

PMID- 16640913
TI  - [Digital pulse wave analyzing method in evaluating arterial compliance based on
      population study in Chinese 415 adults].
AB  - OBJECTIVE: To explore the reliability and validity of digital pulse wave
      analyzing method in evaluating arterial compliance in population-based study.
      METHODS: All 415 adults (132 men and 283 women) aged 20 to 86 years old were
      selected from urban (220 persons) and rural (195 persons) areas, respectively by
      a stratified randomly sampling method. Arterial compliance, evaluated by
      stiffness index (SI), was measured by using digital pulse wave analyzing method
      from the Pulse trace machine (Micro medical, London), and the SI value was
      determined accordingly. RESULTS: In the study on both repeatability and
      stability, there was a perfect correlation between the frequent measurements for
      one individual either on one occasion or on two 40-days-apart occasions. The SI
      values were not significantly different between the urban and the rural, men and
      women. Multiple stepwise regressions showed that systolic blood pressure and age
      were positively correlated with SI value, respectively (both P values were less
      than 0.001). The correlation kept unchanged after taking account of gender, BMI
      and heart rate. The mean SI values for people aged 20 to 29, 30 to 39, 40 to 49,
      50 to 59 and > or = 60 were 7.35, 8.84, 10.41, 10.95 and 12.01 m/s (P < 0.01),
      respectively. CONCLUSIONS: Both systolic blood pressure and age should be
      contributed as the main influencing factors of arterial compliance. Digital pulse
      wave analyzing method is a preferable measurement in evaluating arterial
      compliance in population-based study due to its better repeatability and
      stability.

PMID- 16640925
TI  - [Clinical study of implant-retained facial prosthesis].
AB  - OBJECTIVE: To evaluate clinical results and technical characteristics of implant
      retained facial prosthesis. METHODS: Six patients with facial defects underwent
      implant retained prosthesis treatment, of which 3 orbita defects (including upper
      and lower eyelids, eyeball) in 3 cases, 2 ears defects in 2 cases, and a nose
      defect in one case. Under local anaesthesia 21 extra-oral implant were placed,
      facial prosthesis were individually made six month postoperatively. Follow up
      ranged from 6 month to 6 years. RESULTS: All 21 implants osseointegrated well,
      implant lost and peri implantitis was not found. All 6 cases had individual
      facial prosthesis and were satisfied with the prosthesis. CONCLUSIONS: Extra oral
      implants provided excellent retainment for facial prosthesis; result of current
      silicon with individual color shade is encouragable.

PMID- 16640926
TI  - [Effect of fibrinogen on the adherence of Porphyromonas gingivalis to human oral
      epithelial cells].
AB  - OBJECTIVE: To study the role of fibrinogen molecule in the pathogenesis of
      periodontal diseases. METHODS: An in vitro cell culture model was used. Methyl
      (3)H Thymidine radiolabeled Porphyromonas gingivalis (Pg) ATCC 33277 were
      examined for their ability to adhere to and invade the confluent monolayers of
      human oral epithelial KB cells with or without exogenous human fibrinogens by
      scintillation spectrometry. RESULTS: The addition of exogenous fibrinogens made
      more amount of and higher ratios of adhesive and invasive Pg, in contrast to the
      group without exogenous fibrinogen (P < 0.001). At different concentrations of
      exogenous fibrinogen, the amount and ratios of adhesive and invasive Pg varied
      significantly (P < or = 0.007). The higher concentrations of exogenous fibrinogen
      was added, the greater amount and ratios of adhesive and invasive Pg were found.
      CONCLUSIONS: Fibrinogen promotes the adherence of Pg to human oral epithelial
      cells and may play an important role in the pathogenesis of periodontal diseases.

PMID- 16640927
TI  - [Effects of enamel matrix protein on the growth of human periodontal ligament
      cells on root cementum surfaces].
AB  - OBJECTIVE: To evaluate the effect of enamel matrix protein (EMP) on the
      attachment and proliferation of periodontal ligament cells (PDLC) on diseased
      cementum surfaces in vitro. METHODS: Cementum chips were obtained from diseased
      roots exposed to periodontal pocket. Thirteen diseased root cementum chips were
      conditioned with EMP. Meanwhile, 13 diseased and 13 healthy cementum chips were
      treated with physiological saline as control. The growth and morphology of PDLC
      on the root surface were observed after 24 hours incubation by scanning electron
      microscope (SEM). PDLC attachment and proliferation were quantified using MTT
      assay at 16 or 72 hours. RESULTS: The cells on EMP treated roots under SEM were
      growing robust like the cells on healthy roots. By contrast, the diseased
      cementum surface without conditioned with EMP was only partly covered with
      spindle-shaped cells, with filopodia appearing short and thin. MTT assay
      indicated that the number of adhered and proliferated cells on diseased cementum
      chips treated with EMP was significantly greater than that on diseased chips
      treated with saline (adhesion: 0.45 +/- 0.03 vs. 0.37 +/- 0.05, P < 0.05;
      proliferation: 0.71 +/- 0.02 vs. 0.55 +/- 0.08, P < 0.01), but less than that on
      healthy chips (adhesion: 0.45 +/- 0.03 vs. 0.67 +/- 0.08, P < 0.05;
      proliferation: 0.71 +/- 0.02 vs. 1.05 +/- 0.09, P < 0.05). CONCLUSIONS: It was
      suggested that EMP could promote the growth of PDLC on the diseased root cementum
      surface.

PMID- 16640928
TI  - [The biological changes of NIH3T3 cells co-cultured with human bone morphogenetic
      protein-2 gene transfecting cells].
AB  - OBJECTIVE: To investigate the ultrastructure and the alkaline phosphatase (ALP)
      activity changes of NIH3T3 cells incubated with secretive human bone
      morphogenetic protein-2 (hBMP-2) that is induced by gene transfection through
      transwell system. METHODS: Eukaryotic expression vector (pcDNA3.1-B2) was
      transduced into NIH3T3 cells by Sofast, a positive compound transfection agent.
      The positive cell clones were selected with G418. The cytoplasmic and
      extracellular expression of BMP-2 in the NIH3T3 cells were determined by
      immunohistochemical and enzyme-linked immunosorbent assay (ELISA). NIH3T3 cells
      were co-cultured with hBMP-2 gene transfecting cells through transwell system,
      and the ultrastructure and ALP activity (the markers of osteogenetic
      differentiation) changes were observed. RESULTS: There were cytoplasmic and
      extracellular expression of BMP-2 in transfecting NIH3T3 cells. The
      ultrastructure changes and the high expression of ALP suggested the osteogenetic
      differentiation tendency of NIH3T3 cells co-cultured with transfecting NIH3T3
      cells. CONCLUSIONS: Secretive BMP-2 that is induced by gene transfection could
      promote the osteogenetic differentiation of fibroblast cells.

PMID- 16640929
TI  - [Inhibitory effect of dendritic cell vaccine on the growth of implanted tongue
      squamous cell carcinoma tumors in nude mice].
AB  - OBJECTIVE: To investigate the inhibitory effect of dendritic cells (DCs) on the
      growth of the implanted tongue squamous cell carcinoma (SCC) tumors in nude mice.
      METHODS: Being induced from human peripheral blood monocytes (PBMCs) with rhGM
      CSF, rhIL-4 and rhTNF-alpha, DCs were pulsed by Tca8113 cells lysates. Those DCs
      and T lymphocytes were co-cultured to induce specific cytotoxic T lymphocytes
      (CTLs). Immunotherapy was then performed after those DCs and CTLs were implanted
      into the tumor-bearing nude mice. RESULTS: DCs were induced from PBMCs with
      multiple cytokines. Compared with the control groups, the growth of tumors was
      significantly inhibited in the group that had been implanted with DCs and CTLs,
      and tumor doubling time also increased markedly (P < 0.05). CONCLUSIONS: DCs
      function normally after being induced from human PBMCs with multiple cytokines;
      DCs pulsed with tumor cell lysates and CTLs co-cultured with those DCs have a
      significant anti-tumor immune activity in nude mice.

PMID- 16640930
TI  - [Computer-aided mandibular repositioning system for efficacy prediction of oral
      appliance in patients with obstructive sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To develop a computer-aided mandibular repositioning system (CAMRS)
      and investigate its preliminary application in efficacy prediction of oral
      appliance in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).
      METHODS: CAMRS was mainly consisting of a step motor and a screw that was remote
      controlled by a computer. This system could work with polysomnography (PSG).
      Fourteen OSAHS patients diagnosed by PSG were recruited. With CAMRS, six
      mandibular positions were titrated with PSG for every hour. RESULTS: Stable
      mandible positioning and little sleeping disturbance were observed. Apnea
      hypopnea index (AHI) was improved progressively with mandibular advancement. The
      extent of mandibular advancement was correlated with the severity of OSAHS (r =
      0.72747). CONCLUSIONS: CAMRS could reproductively and effectively reposition
      mandible with little sleeping disturbance. Through CAMRS, an individualized
      optimal mandibular position could be obtained for each OSAHS patient treated with
      oral appliance.

PMID- 16640931
TI  - [Influences of orthodontic tooth movement on estrous cycle and estrogen in rats].
AB  - OBJECTIVE: To explore the influences of orthodontic tooth movement on estrous
      cycle and estrogen in female rats. METHODS: Two hundred female rats were divided
      into control group, one-time activation group, four-time activation group and
      sham-operated group. Each group was divided again into 4 sub-groups according to
      the different stage of the estrous cycle. The force-loading groups received
      repeated intermittent force. Serum estrogen was measured and the change of
      estrous cycle was recorded. RESULTS: There were significant variations in the
      estrogen level among the groups which received mechanical force during the same
      stage of the estrous cycle (P < 0.01) and among the subgroups within each group
      (P < 0.05). These experimental treatments affected the estrous cycle of the rats
      in the groups received force in metestrus and diestrus. CONCLUSIONS: Estrus of
      rats was the appropriate time for the orthodontic force.

PMID- 16640932
TI  - [Effect of bioactive glass filling defective alveolar bone on tooth movement].
AB  - OBJECTIVE: To observe the movement of rat's tooth in the area of defective
      alveolar bone filled with bioglass in comparison with contralateral tooth.
      METHODS: Forty female Wistar rats were selected. Defects in alveolar bones were
      created and filled with bioglass. Orthodontic appliances were fixed to mesially
      guide the maxillary first molars. RESULTS: The rats' teeth were mesially moved in
      the area filled with bioglass. There were no significant differences between two
      sides in movement distance of the first molars and in thickness of periodontal
      tissues with paired t-test (P > 0.05). CONCLUSIONS: The rat's tooth can be
      mesially moved in the area filled with bioglass.

PMID- 16640933
TI  - [Repair of canine segmental mandibular defects using autogenous bone marrow
      stromal cells and coralline hydroxyapatite].
AB  - OBJECTIVE: To repair segmental mandibular defects with autogenous bone marrow
      stromal cells (BMSCs) and coralline hydroxyapatite. METHODS: Isolated BMSCs were
      in vitro expanded and osteogenically induced. In 11 canines, a 3 cm segmental
      mandibular defect in right mandible was created. Five canine's defects were
      repaired with cell-scaffold constructs made from induced BMSCs and coralline
      hydroxyapatite (CHA); Others were repaired with CHA as control. The engineered
      bone was evaluated by X-ray, CT, gross and histological examination,
      biomechanical test 12, 26, 32 weeks post-operation respectively. RESULTS: BMSCs
      grew well on the CHA. X-ray and CT images showed better callus formation at
      connection sites in experimental group over time while worse formation at
      connection sites eventually in control group. At 32 weeks post-operation in
      experimental group, the defects were well repaired grossly. Histologically, there
      were bony healing and lamellar bone formation, in experimental group fibrous
      healing and woven bone formation in control group. Biomechanical test revealed no
      significant difference between experimental group and normal control group.
      CONCLUSIONS: Canine segmental mandibular defects can be ultimately repaired with
      the tissue-engineered bone generated by autogenous osteogenic BMSCs and CHA
      scaffold.

PMID- 16640934
TI  - [Repair of peripheral nerve defect by a scroll of amnion derivative compound with
      cultured autogenous Schwann cell in a rat model].
AB  - OBJECTIVE: To test a nerve bridge substitute for peripheral nerve repair by
      tissue-engineering approach. METHODS: An artificial nerve fabricated with a
      scroll of amnion derivative (ZQ membrane) and cultured autogenous Schwann cell
      was sutured to bridge sciatic nerve defect of 2.5 cm in length in rats. The
      specimens were assessed with tracking study, histology, electrophysiological
      technique, NF200, and synaptophysin-38 (SYP) immuno histochemical staining 3
      months postoperatively. RESULTS: The regenerated nerve sprouted 3 months after
      the operation. The regenerated nerve fibers were plentiful and could grow into
      the recipient nerve and target muscle's motor end plate (MEP) areas to
      reinnervate target muscle, and reconstruct function of nerve-muscle junction.
      Functional recovery could reach to 40%-60% of normal control. Nerve-muscle
      conduction velocity (N-MCV) arrived at 21.77 +/- 1.15 m/s. CONCLUSIONS: A tissue
      engineering material fabricated with a scroll of ZQ membrane and cultured
      autologous Schwann cell may be a useful substitute for nerve repair.

PMID- 16640935
TI  - [Immunohistochemical analysis of cell cycle-associated proteins p27 in oral
      cancer and precancer].
AB  - OBJECTIVE: To evaluate the expression of p27 protein in oral precancerous lesions
      and oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was used
      to detect p27, p53, murine double minute (MDM2) and p21 protein expression in a
      series of 13 specimens with simple hyperplasia, 44 with dysplasia and 48 with
      OSCC. An attempt was made to correlate the protein levels with clinicopathologic
      parameters and Ki-67 protein levels. RESULTS: Positive p27 staining was present
      in 79.55% of the dysplasia samples, as well as in 81.25% of the OSCC samples. p27
      protein overexpression in OSCC group was significantly higher than that in
      leukoplakia group (P < 0.001). The extent of p27 expression was positively
      associated with Ki-67 expression (P < 0.001). Cases with p27 overexpression
      displayed concurrent expression of p53 and/or MDM2 (P = 0.034) in OSCC group.
      CONCLUSIONS: p27, p53, MDM2 and p21 may all play important roles in the genesis
      of OSCC. The alterations of one or more cell cycle regulators are prevalent in
      oral premalignant lesions and OSCC and the regulators can regulate each other.

PMID- 16640936
TI  - [Expression of stromal CD34 and alpha-smooth muscle actin in oral invasive
      cancer].
AB  - OBJECTIVE: To observe the expression of stromal CD34 and alpha-smooth muscle
      actin (alpha-SMA) in oral invasive cancer. METHODS: The distribution and
      expression of stromal CD34 and alpha-SMA in 60 patients with invasive oral
      squamous cell cancer and 20 resections with tumor-free margins from 60 patients
      with invasive oral squamous cell cancer were examined by immunohistochemistry SP
      method. RESULTS: Twenty cases of resections of mucosa with tumor-free margins
      exhibited CD34 expression in fibrocytes cytoplasm in the vicinity of vessels,
      mucosa and submucosa but were free of alpha-SMA expression, only the walls of
      muscularized vessels stained positive for alpha-SMA in the stroma. Sixty invasive
      oral squamous cell carcinomas were free of stromal CD34 expression, only the
      endothelia of small vessels stained positive for CD34, of which 53 invasive oral
      squamous cell carcinomas expressed stromal alpha-SMA in myofibroblasts cytoplasm.
      CONCLUSIONS: The detection of CD34 and alpha-SMA is an adjunctive tool in judging
      oral cancer invasion in small oral mucosa biopsy specimens based on the absence
      of CD34 expression paralleled by the gain of alpha-SMA in the stroma of oral
      invasive cancer.

PMID- 16640937
TI  - [Clinical application of electrosonography in diagnosis of anterior disc
      displacement with reduction].
AB  - OBJECTIVE: To investigate the electrosonography character of sounds emanating
      from anterior disc displacement with reduction of TMJ and the value of it in
      clinical diagnosis. METHODS: The sounds from healthy TMJ, anterior disc
      displacement with or without reduction of TMJ, and osteoarthritis of TMJ were
      recorded and analyzed by K6-I system, then the data was used for diagnosis of
      anterior disc displacement with reduction in clinic. RESULTS: A special kind of
      waveform was found in the electrosonography of sounds from anterior disc
      displacement with reduction repeatedly, and seldom or not in sounds from healthy
      joints, anterior disc displacement without reduction or osteoarthritis of TMJ.
      The diagnostic sensitivity of anterior disc displacement with reduction by using
      electrosonography analysis was 77.2% and specificity was 93.3% when compared with
      the clinical diagnosis based on clinical appearance and radiography evidence.
      CONCLUSIONS: The special kind of waveform may be characteristic wave of sounds
      from anterior disc displacement with reduction of TMJ, which is useful for
      assistant diagnosis of anterior disc displacement with reduction in clinic.

PMID- 16640938
TI  - [Development of a novel in-vitro culture device simulating distraction
      osteogenesis and expression of osteoblast cytoskeleton].
AB  - OBJECTIVE: To establish a novel in-vitro culture device simulating distraction
      osteogenesis, and to understand the the changes of cytoskeleton of osteoblasts
      under different magnitudes of mechanical distraction. METHODS: A novel in-vitro
      culture device simulating distraction osteogenesis was developed with titanium
      and silicon membrane. The expressions of F-actin cytoskeleton subjected to
      different magnitudes of distraction were observed in situ under a confocal laser
      scanning microscope, and protein levels of actin and tubulin alpha were analyzed
      by electrophoresis of Western blot. RESULTS: The mode of culture device
      simulating distraction osteogenesis was similar to that of distraction
      osteogenesis used in clinic. After 24 h mechanical distraction with physiological
      magnitude, F-actin of osteoblasts was organized and paralleled to the direction
      of distraction forces. After 24 h mechanical distraction with hyperphysiological
      magnitude, however, F-actin of osteoblasts became reorganized and disrupted, and
      protein levels of actin and tubulin alpha decreased. CONCLUSIONS: The novel in
      vitro culture device simulating distraction osteogenesis is suitable for the
      study of distraction osteogenesis in vitro. Physiological mechanical distraction
      causes organization and rearrangement of actin cytoskeleton. However,
      hyperphysiological mechanical distraction results in reorganization and
      disruption of actin cytoskeleton.

PMID- 16640939
TI  - [An experimental study on alveolar ridge preservation prior to dental implant
      placement].
AB  - OBJECTIVE: To evaluate the combination of surgical grade calcium sulfate
      hemihydrate (SGCS) and platelet-rich plasma (PRP) for alveolar ridge preservation
      prior to implant placement. METHODS: Changes of bone quantity and quality in
      extraction sites following the SGCS/PRP and SGCS implantations were investigated
      by spiral computer tomography scan, bone scintigraphy, radiographic, histological
      and histomorphometric examinations. RESULTS: The placement of SGCS/PRP reduced
      the resorption of the alveolar ridge. It also promoted bone metabolism and bone
      to-implant contact. The addition of PRP to SGCS achieved the enhancement of the
      bone metabolism only at the early healing phase. CONCLUSIONS: In this animal
      experiment, SGCS/PRP may be used as fresh extraction sockets graft for alveolar
      ridge preservation prior to implant placement.

PMID- 16640940
TI  - [Preventive effect of genistein on malignant transformation of oral leukoplakia].
AB  - OBJECTIVE: To investigate the preventive effect of genistein on the malignant
      transformation of oral leukoplakia in hamster cheek pouch. METHODS: Sixty male
      Syrian golden hamsters were randomly divided into 4 groups, with two of 20 and
      two of 10. DMBA solution (0.5% in acetone) was applied topically to the left
      cheek pouch of male Syrian golden hamsters in group A and B, while animals in
      group C were painted with acetone, 3 times a week for 6 weeks. For the next 12
      weeks, animals in group B received genistein (10 mg.kg(-1).d(-1)) daily by
      gavage; animals in group A and C received same volume of saline; animals in group
      D serving as blank control. At the end of the experiment, animals were sacrificed
      and tissue samples were collected for histopathological examination. RESULTS: No
      significant differences in the tumor latency and tumor incidence were observed
      between the control and genistein treated group. CONCLUSIONS: No inhibitory
      effect of genistein on the transformation of oral leukoplakia was observed in
      hamster.

PMID- 16640941
TI  - [Endodontic treatment: Part I. Configuration, diagnosis and treatment of C-shaped
      canals].

PMID- 16640942
TI  - [Basic principles of orthodontics: Part I. Diagnosis and treatment planning in
      orthodontics].

PMID- 16640943
TI  - [How to write medical paper: Part II. Form and methods].

PMID- 16640944
TI  - [Giant cell lesions of jaw].

PMID- 16640945
TI  - Baseball and softball injuries.
AB  - Baseball and softball injuries can be a result of both acute and overuse
      injuries. Soft tissue injuries include contusions, abrasions, and lacerations.
      Return to play is allowed when risk of further injury is minimized. Common
      shoulder injuries include those to the rotator cuff, biceps tendon, and glenoid
      labrum. Elbow injuries are common in baseball and softball and include medial
      epicondylitis, ulnar collateral ligament injury, and osteochondritis dissecans.
      Typically conservative treatment with relative rest, medication, and a
      rehabilitation program will allow return to play. Surgical intervention may be
      needed for certain injuries or conservative treatment failure.

PMID- 16640946
TI  - Professionalism and the ethics of the sideline physician.
AB  - The physician working on the sidelines of a public sporting event may encounter a
      unique set of ethical dilemmas. Many of the ethical pitfalls result from the
      physician's responsibilities, not only to the patient, but also to teams and
      events. Standard rules of confidentiality and patient autonomy may not apply. We
      propose the use of professionalism as a guide for the sideline physician when
      faced with difficult ethical situations.

PMID- 16640947
TI  - Medical coverage of cycling events.
AB  - Medical coverage of recreational and competitive cycling events requires
      significant planning and cooperation among the race and medical directors, race
      officials, and local emergency medical services. The medical team should be
      proficient in treating minor and self-limiting injuries such as abrasions and
      minor trauma. The medical team should also have contingency plans for medical
      emergencies, such as cardiac events and major trauma, that ensure rapid
      stabilization and transport of the athlete to the appropriate medical facility.
      Stationary and mobile medical teams may be necessary for proper coverage of the
      event. Event day communication systems between individual medical staff as well
      as race officials and local emergency medical services is important to the
      success of the event.

PMID- 16640948
TI  - Medical coverage of tennis events.
AB  - Numerous considerations are involved in the coverage of a tennis event, much like
      other sporting competitions. Appropriate equipment within a tournament format is
      examined. The simultaneous play of multiple tennis matches requires rapid access
      to injured players and is facilitated by good communication. Medical time-outs
      present a unique challenge, and awareness of these rules is essential in
      providing care. Common musculoskeletal injuries specific to tennis are reviewed.
      With the potential for high temperatures and dehydration during tennis matches,
      heat illness is also considered.

PMID- 16640949
TI  - Management of lower extremity malalignment during running with neuromuscular
      retraining of the proximal stabilizers.
AB  - This case report presents a high-level female runner with a history of more than
      25 years of recurrent lower extremity (LE) injuries and LE malalignment problems
      during running. Due to her LE malalignment, she has been unable to run for the
      past 3 years. A definitive diagnosis was not found for her inability to run so by
      exclusion we diagnosed dysfunction of the hip, spine, and pelvic stabilizers that
      resulted in her in LE malalignment. To treat this muscle weakness, we designed a
      Pilates-evolved functional movement intervention to improve the control and
      strength of the proximal stabilizers and regain normal LE alignment. The Pilates
      evolved treatment approach involved a series of functional and progressive
      resistance exercises designed to dynamically stabilize the spine, pelvis, and hip
      through all planes of motion. After 1 year of Pilates-evolved training, the
      athlete's disabling movement pattern resolved and she has returned to a regular
      running program. The purpose of this case report is to describe a Pilates-evolved
      functional movement intervention that resolved this runner's LE malalignment and
      returned her to running when other traditional treatment approaches were not
      effective in doing so.

PMID- 16640950
TI  - Stretching for performance enhancement.
AB  - Stretching exercises have been considered an essential component of physical
      training programs for decades. Cross-sectional studies have demonstrated that
      flexibility measures are related to performance in many sports, suggesting that
      using stretching to enhance flexibility may indirectly improve performance.
      However, observations by athletes and coaches have called into question the
      universal prescription of stretching for the purpose of enhancing sport
      performance, and this skepticism is being supported by a growing body of
      empirical data. Whereas the tissue responses and adaptations to stretching have
      been the most widely studied area of stretching research, comparatively little is
      understood regarding the neural influences on range of motion, which may have
      more applicability when the range of motion needs are related to skilled
      movements as in sport.

PMID- 16640951
TI  - A plyometric training model used to augment rehabilitation from tibial fasciitis.
AB  - Shin splints, an exercise-induced form of lower leg pain, is a common complaint
      among athletes. Considered an overuse injury that compromises the dense and tough
      fascial attachments of the tibialis posterior and/or tibialis anterior muscles
      from the tibia, it responds well to a multiphase treatment plan that incorporates
      plyometric strengthening and conditioning exercises. Plyometrics may be safely
      introduced as early as the third or functional phase of recovery. A progressive
      plyometric program that emphasizes a gradual development of eccentric stress
      loading to the musculoskeletal components of the deep posterior and anterior
      muscle compartments of the lower leg is described.

PMID- 16640952
TI  - Prehabilitation: preparing young athletes for sports.
AB  - Great athletes may be born and not made, but I believe that there are many with
      great potential who succumb to noncontact injury through poor training habits, or
      as a result of correctable biomechanical imbalances. Preparing an athlete for
      sports requires medical and orthopedic evaluation, assessment of fitness for
      competition, and education in the principles of proper training. Because few
      individuals have access to a comprehensive sports medicine center, primary care
      physicians should familiarize themselves with the principles of prehabilitation
      to help young athletes prevent injury and realize their full potential.

PMID- 16640953
TI  - Training the gut for competition.
AB  - The gut is an important athletic organ because it mediates water and nutrient
      uptake during exercise. But upper- and lower-gastrointestinal complaints, common
      to many athletes during exercise, can negatively impact performance, and in
      severe cases put health at risk. The gut is sensitive to water and nutrient
      intake during exercise and to hypovolemia, hyperthermia, hypoglycemia, hypoxia,
      and ischemia. Most gastrointestinal complaints during exercise are mild and of no
      risk to health, but hemorrhagic gastritis, hematochezia, and ischemic bowel can
      present medical challenges. Proper training and nutrition minimize the risk of
      gastrointestinal discomfort during exercise by assuring rapid gastric emptying
      and absorption of water and nutrients and by maintaining adequate perfusion of
      the splanchnic vasculature.

PMID- 16640954
TI  - Genetic markers of oxidative stress and coronary atherosclerosis.
AB  - Atherosclerosis, the primary cause of coronary artery disease (CAD), is a
      multifactorial disease, the molecular etiology of which involves interaction of
      many genes and environmental factors. Reactive oxygen species are integral to
      many cellular and biomolecular processes that are active in the transition of
      incipient fatty streaks into acute coronary syndromes. Animal models of
      atherosclerosis and correlative data from human studies support the oxidative
      stress hypothesis of atherosclerosis. However, the association of genetic
      polymorphisms that underlie enhanced oxidative stress with CAD is controversial.
      In this review, we discuss polymorphisms in genes that are main sources of
      reactive oxygen species generation (NADH oxidase, endothelial nitric oxide
      synthase, and myeloperoxidase) in mitochondria and the antioxidant enzymes
      paraoxonase, glutathione reductase, and heme oxygenase. The contribution of
      defined genetic variants involved in oxidative homeostasis to human
      atherosclerosis susceptibility is modest because regulation of oxidative stress
      is multifactorial. However, the contribution of genetic haplotypes in concert
      with environmental factors is likely significant. A more rigorous
      characterization of genetic and oxidative phenotypes together with
      characterization of novel gene polymorphisms may help in early therapeutic
      intervention for CAD.

PMID- 16640955
TI  - Nonconventional genetic risk factors for cardiovascular disease.
AB  - Despite numerous advances made in identifying the genes for rare mendelian forms
      of cardiovascular disease (CVD), relatively little is known about the common,
      complex forms at the genetic level. Moreover, most genes that have been
      associated with CVD, whether they are single gene forms or more common forms of
      the disease, have primarily been involved in biochemical pathways related to what
      are considered "conventional" risk factors. However, recent genetic studies have
      begun to identify genes and pathways associated with CVD that would not be
      considered to underlie conventional risk factors. In this review, we discuss the
      evidence for this latter notion based on recent linkage and association studies
      in humans. As an example, we also illustrate how a combination of mouse and human
      genetics led to identification of the 5-lipoxygenase pathway for CVD, with
      potentially important implications for its treatment and diagnosis. We conclude
      with a discussion of the prospects for identifying CVD genes in the future and
      for potentially developing more effective therapeutic strategies.

PMID- 16640956
TI  - Genetic susceptibility to thrombosis.
AB  - Thrombosis is associated with atherosclerosis, sepsis, cancer, and numerous other
      inflammatory diseases. Complications of thrombosis, such as myocardial
      infarction, stroke, and venous thromboembolism, contribute significantly to
      morbidity and mortality. Susceptibility to thrombosis is conferred by both
      genetic and environmental factors. Tissue factor is the primary cellular
      initiator of blood coagulation and is a major contributor to thrombosis. In this
      review, we discuss the association between various polymorphisms and the risk for
      thrombosis.

PMID- 16640957
TI  - Genetic determinants of carotid ultrasound traits.
AB  - Atherosclerosis is a complex disease with various intermediate phenotypes that
      are themselves complex and influenced by many factors. Through the use of carotid
      ultrasound techniques, the intermediate stages of vascular disease can be imaged
      and studied for association with potential genetic determinants. In this article
      we review the most recent available data (reports published since 2004) on the
      genetic determinants of atherosclerosis, as measured by one-, two-, and three
      dimensional ultrasonography of the carotid arteries. In general, associations are
      disparate and modest. For intima-media thickness, promising associations have
      been found for both TNFRSF1A R92Q and PPARG P12A, but associations also differed
      in the same individuals depending on the specific ultrasound trait studied (eg,
      linear intima-media thickness versus total plaque volume in carotid arteries).
      Some of the challenging issues for future studies include accounting for gene
      environment interactions, sex-specific associations, and the distinctiveness of
      different carotid ultrasound measures.

PMID- 16640958
TI  - Field of confusion: future prospects for fibrate therapy in cardiovascular
      disease.

PMID- 16640959
TI  - Oxidized lipids: the two faces of vascular inflammation.
AB  - Elevated plasma levels of low-density lipoprotein and generation of oxidized low
      density lipoprotein have been directly associated with the pathogenesis of
      atherosclerosis, and lipid oxidation products have been directly linked with
      induction and propagation of monocytic subendothelial accumulation and other
      inflammatory reactions associated with chronic vascular inflammation. However,
      accumulating data suggest that oxidized lipids may also exhibit anti-inflammatory
      potential and serve as potent inhibitors of nuclear factor-kappaB-dependent
      proinflammatory cascade. In addition, we have characterized a group of bioactive
      components of oxidized phospholipids with barrier-protective effects towards
      endothelial cells in the models of agonist-induced endothelial permeability and
      lipopolysaccharide-induced lung dysfunction. This review discusses the role of
      oxidized lipids in the progression of atherosclerosis as well as the important
      anti-inflammatory effects of oxidized phospholipids and their potential role in
      the modulation of vascular barrier integrity.

PMID- 16640960
TI  - The ligand/RAGE axis: lighting the fuse and igniting vascular stress.
AB  - Vascular inflammation contributes critically to the initiation and progression of
      atherosclerosis. These processes are accelerated in hyperglycemia and play key
      roles in the increased incidence and severity of myocardial infarction and stroke
      observed in diabetes. Evidence suggests that the ligands of the receptor for
      advanced glycation endproducts (RAGE), a multiligand member of the immunoglobulin
      superfamily, interact with this receptor to play important roles in both early
      development and progression of atherosclerosis and vascular inflammation. Studies
      in animal models of vascular injury underscored the potent impact of RAGE
      blockade; administration of ligand-binding decoys of RAGE or antibodies to the
      receptor reduced the consequences of diabetes, hyperlipidemia, and physical
      injury to the vessel wall. This review focuses on the ligand repertoire of RAGE,
      the impact of ligand-RAGE interaction, and the potent effect of RAGE blockade in
      rodent models of vascular injury.

PMID- 16640961
TI  - Vascular shear stress and activation of inflammatory genes.
AB  - Atherosclerotic lesions form preferentially at distinct sites in the arterial
      tree, especially at or near branch points, bifurcations, and curvatures where
      there is disturbed or oscillatory blood flow. In contrast, straight regions of
      the vasculature exhibit uniform laminar shear stress, which is atheroprotective.
      The ability of laminar flow to exert an anti-inflammatory effect on the
      endothelial cell lining of the blood vessel is revealed by preventing monocyte
      adhesion, proliferation, and apoptosis. Changes in endothelial cell gene
      expression in response to laminar shear stress reflect these changes in cell
      physiology with the demonstration that physiologic flow inhibits the expression
      of inflammatory genes. Thus, shear stress is critically important in regulating
      vascular physiology and pathobiology of the vessel wall via the modulation of
      endothelial cell gene expression.

PMID- 16640962
TI  - Cyclooxygenase-2 inhibition: vascular inflammation and cardiovascular risk.
AB  - The inducible isoform of cyclooxygenase-2 (COX-2) plays a role in
      pathophysiologic processes like inflammation and pain but is also constitutively
      expressed in tissues such as the kidney or vascular endothelium, where it exerts
      important physiologic functions. Although much evidence exists that implicates
      COX-2 in atherosclerosis, its role in this setting remains substantially
      uncertain. This observation is also confirmed by the results of clinical trials
      of selective COX-2 inhibitors. Treatment with these drugs, developed with the
      assumption that they would be as effective as nonselective COX inhibitors but
      without their gastrointestinal side effects, has been reported to be associated
      with an increased cardiovascular risk. In this article, we review the pattern of
      expression of COX-2 in the cellular players of atherothrombosis, its role as a
      determinant of plaque vulnerability, and the vascular effects on prostanoid
      inhibition by COX-2 inhibitors.

PMID- 16640966
TI  - [Quality and specialization in health care].

PMID- 16640963
TI  - Transcription factor and kinase-mediated signaling in atherosclerosis and
      vascular injury.
AB  - Our understanding of the molecular signaling pathways regulating the initiation
      and progression of atherosclerosis or remodeling in response to injury has begun
      to cross the boundaries from regulation of well-described canonical pathways to
      the interplay between these pathways. The focus of this review is to summarize
      our current understanding of a finite group of transcription factors and kinases
      involved in vascular injury and atherosclerosis, including nuclear factor-kappaB
      (NF-kappaB), early growth response factor-1 (Egr-1), activator protein-1 (AP-1),
      hypoxia inducible factor-1alpha (HIF-1alpha), homeobox, and T cell
      factor/lymphoid enhancer factor (Tcf-Lef), as well as the kinases janus
      kinase/signal transducers and activators of transcription (JAK/STAT), protein
      kinase C (PKC), p38, Rho, ERK5, JNK, p44/p42, and phosphoinositide 3 (PI3)
      kinase/AKT.

PMID- 16640967
TI  - [Treatment centralization in health care].

PMID- 16640968
TI  - [The importance of centralized treatment: research and development].
AB  - Biomedical research in Denmark enjoys a strong position at present but will be
      challenged by a new organization for all hospitals in Denmark beginning in 2007.
      It will be very important to recognize the importance of medical research as the
      cornerstone of optimal patient treatment in the new hospital organizations.
      Centralization with a focus on efficiency and low cost, as well as
      decentralization combined with the loss of university hospital functions, will
      further challenge the conditions of clinical research already seen worldwide and
      also experienced in Denmark.

PMID- 16640969
TI  - [Gastrointestinal surgery--why specialisation?].
AB  - Recent international data have documented improved postoperative outcome in
      relation to hospital and surgeon volume. Nation-wide Danish data have documented
      a high mortality and long hospital stay after abdominal cancer surgery, which is
      performed in a large number of departments. It is concluded that reorganisation
      with fewer surgical departments is required to improve outcome after major
      gastrointestinal surgery.

PMID- 16640970
TI  - [Centralisation of vascular surgical treatment provides better results].
AB  - The relation between higher hospital and surgeon volume for better results after
      vascular surgery has been documented in some areas. In the case of surgery for
      stenosis of the carotid artery surgeon volume has been found to be inversely
      related to the postoperative frequency of stroke and death (low volume <6-12
      yearly), whereas the relation to hospital volume is more uncertain. For surgery
      of abdominal aortic aneurysms the same relationship has been documented for
      hospital volume (low volume <approx. 20 yearly), where the relation to surgeon
      volume is more uncertain. In Denmark, with vascular surgery being centralised to
      9 departments, all departments fulfil the criteria for being high-volume
      hospitals, and most surgeons do the same. It is only in Carotid surgery that
      (1/3) of surgeons do not operate more than 10 patients a year.

PMID- 16640971
TI  - [The connection between hospital volume and outcome in thorax surgery].
AB  - A review of current literature with respect to a possible correlation among
      hospital volume, caseload and outcome of thoracic and cardiovascular surgery
      supports quite convincingly the theory that, from a probability point of view,
      the combination of high-volume hospitals with high-volume surgeons produces the
      best results. During the last decade, thoracic and cardiovascular surgery has to
      a certain degree been centralized in Denmark, reducing the number of public
      centres to the five university hospitals. None of these centres is low-volume,
      and two are high-volume hospitals.

PMID- 16640972
TI  - [Nephrectomy in denmark 2002-2005].
AB  - INTRODUCTION: Implementation of principles of fast-track surgery as well as
      laparoscopy may decrease hospital stay after nephrectomy to about 2-4 days. The
      aim of this study was to analyse the incidence, use of laparoscopic vs. open
      nephrectomy, hospital stay, morbidity and mortality in Danish hospitals within
      the period 2002-2005. METHODS: Extraction of information from the National
      Patient Register (LPR) and discharge notes from Jan. 1 2002 to Dec. 31 2004.
      RESULTS: In the 3-year period, 1968 nephrectomies were performed in a total of 45
      departments, decreasing to 29 departments in 2004. Five departments performed >
      100 operations during the 3 years, 10 departments performed between 50-100
      operations and 30 departments <50 operations during the 3 years. The average
      length of hospital stay (primary and readmission) was 9.1 days. The total
      mortality rate was 2.2%; lower (1.5%) in departments with high activity vs.
      departments with low activity (4.3%, p < 0.01). Laparoscopic surgery was
      performed in 11 departments with a hospital stay of 5.2 vs. 9.5 days and with
      fewer surgical and medical complications and mortality (0.4% vs. 2.5%), compared
      with open operation. CONCLUSION: The organisation and results after nephrectomy
      are not optimal on a nationwide basis. This precludes further optimisation of the
      early perioperative results, including use of the laparoscopic approach combined
      with the principles of fast-track surgery. It is suggested that nephrectomy in
      the future is performed in fewer departments to fulfil these needs.

PMID- 16640973
TI  - [Performing major upper abdominal operations in a low-volume hospital: is it
      possible?].
AB  - INTRODUCTION: The outcomes of cardio-oesophageal resection, gastric resection,
      total gastrectomy and Whipple's operation in a low-volume hospital over a decade
      are presented. MATERIALS AND METHODS: Thirty-seven patients were followed for
      five years after a cardio-oesophageal resection, 21 after a Billroth II
      resection, 15 after total gastrectomy and 28 after a Whipple's operation.
      Mortality and morbidity rates, post-operative in-hospital period and long-term
      survival were measured. RESULTS: Cardio-oesophageal resection: The morbidity rate
      was 19%, the mortality rate was 11%, and the median post-operative stay in
      hospital was 11 days. The five-year survival rate based on death from cancer was
      37% and from all causes 32%. Gastric resection and gastrectomy: The morbidity
      rate was 14%, the mortality rate was 3%, and the median post-operative period in
      hospital was 9 days after gastric resection and 11 days after gastrectomy. The
      five-year survival rate based on death from was cancer 55% and from all causes
      37%. Whipple's procedure: The morbidity rate was 17%, the mortality rate was 4%
      and the median post-operative stay in hospital was 10 days. The survival rate
      based on death from cancer was 77% and from all causes was 54% after five years
      for cancer of the ampulla of Vater, and 27% and 31% after three years for
      pancreatic head carcinoma. CONCLUSION: Major gastric and pancreatic operations
      can be performed in a low-volume hospital with satisfactory results.

PMID- 16640974
TI  - [Accelerated course after operation for ovarian cancer].
AB  - INTRODUCTION: Introduction of principles for postoperative multimodal
      rehabilitation (fast track surgery) has decreased hospital stay from about 8-10
      days to 2-4 days after colonic resection. The aim of this study was to
      investigate the effect of a similar fast track regimen in patients operated for
      ovarian cancer. METHOD: 72 consecutive patients operated with a conventional
      perioperative treatment regimen (group 1) were compared with the initial 69
      consecutive patients (group 2) with a multimodal rehabilitation regimen and the
      next 50 consecutive patients (group 3) where the fast track regimen was
      implemented as a routine. RESULTS: Patients demographics and surgical
      characteristics were comparable between groups. Median postoperative hospital
      stay was reduced from six days in group 1, to five days in group 2, and four days
      in group 3 (p < 0,05). Surgical complications were similar while medical
      complications were reduced from 12% to 1% (p < 0,05) and readmissions from 10% to
      2% (p < 0,05) with the fast track regimen. CONCLUSION: Principles for
      postoperative multimodal rehabilitation from colonic surgery lead to faster
      rehabilitation, decreased risk of medical complications and hospital stay in
      patients operated for ovarian cancer.

PMID- 16640975
TI  - [Ovarian cancer in Denmark. Status of the surgical intervention].
AB  - INTRODUCTION: In Denmark women have not only one of the highest risks of ovarian
      cancer but also the highest mortality rate. The primary surgery is a key factor
      in the outcome. MATERIALS AND METHODS: Surgery for the treatment of ovarian
      cancer in Denmark was evaluated for the period from 1 July 2002 to 31 December
      2003 using data from the Danish National Patient Registry
      (Landspatientregisteret, LPR) as well as the letter with the discharge note. The
      analysis included all primary surgical procedures during this period where
      information about number of surgical procedures per department, post-operative
      hospital stay, complications and mortality were obtained. RESULTS: 765 women,
      mean age 61 years (range 5-96 years), were operated on for ovarian cancer. The
      operations were distributed among 52 different hospital departments, and the
      surgery for advanced stage III patients took place in 32 different departments.
      The mean postoperative hospital stay was 9.0 days; 28% experienced one or more
      complications, and 8.1% were reoperated. The mortality rate was 4.2%. CONCLUSION:
      This first nationwide evaluation of surgery for ovarian cancer in Denmark showed
      that the surgery took place in far more hospital departments than the five
      recommended by the Danish National Board of Health. There seems to be room for
      improvement of quality, and a plan for the next five years is presented.

PMID- 16640976
TI  - [Paediatrics. Centralisation of treatment].
AB  - Today there are 19 paediatric departments in Denmark. Most of the children's
      departments are placed in obsolete buildings. Centralisation in children's
      hospital provides a child-oriented environment with staff, who are knowledgeable
      about the needs of children, have the competence in both basic and highly
      specialised medical care, there will be greater opportunities to conduct research
      in children's diseases and be at the cutting-edge of both national and
      international excellence in the paediatric area of specialisation, accomplishing
      this ambition through research and medical improvements.

PMID- 16640977
TI  - [Organisation of treatment of newborns].
AB  - The total number of births in Denmark in 2004 was 60,670. It is a challenge to
      organise neonatal care in such a way that the great majority of healthy normal
      newborns can be born into their families with a minimum of disturbance from the
      health care system. A need for treatment after birth, however, is not uncommon
      (10-15%) and can occur unexpectedly. In this context, it is an advantage that 99%
      of births take place in hospitals, but it is a neonatologic viewpoint that all
      births should take place in hospitals with a neonatal special care unit. There
      are presently 17 neonatal special care units and 33 delivery units in Denmark.
      International experience shows that about 1% of all newborns require intensive
      care, and the current numbers from the new national database of disease-related
      groups classification in Denmark are in agreement. The database indicates that
      59% (394 of 663) of the newborn intensive care in 2004 was provided by
      Rigshospitalet (Copenhagen University Hospital) and the university hospitals of
      Odense and Skejby. The restrictive use of mechanical ventilation in Denmark, the
      short geographical distances and the short working hours of physicians may all be
      good reasons for this centralisation.

PMID- 16640978
TI  - [Optimising treatment for people with rare diseases].
AB  - Diagnosis of and care for people with rare diseases are a challenge. Most rare
      diseases are inherited with clinical presentation in early childhood, complex
      with involvement of several organ systems and progressive with ever changing
      phenotype. Physical and neurological disability makes many families dependent on
      social security. In Denmark and in a few other EU countries, centres of reference
      for the care of people with rare diseases have been established. The impression
      is that the effect of establishing such centres for these rare diseases in
      Denmark has been good and that it remains the most rational way of treatment.

PMID- 16640979
TI  - [Centralization versus decentralization. Hematology].
AB  - Clinical haematology is the result of teamwork among dedicated specialists in
      pathology, molecular diagnostics, imaging, radiotherapy and the haematologist,
      who in turn can focus on only a limited fraction of the various and highly
      complex diseases that together constitute clinical haematology. The treatment of
      patients should be centralized in departments large enough to permit internal
      subspecialization and to provide expert service focused on haematology. No more
      than three such hematology centers are needed in Denmark.

PMID- 16640980
TI  - [Centralisation within the field of pulmonary medicine].
AB  - In Denmark tuberculosis is rare, with 7.3 cases per 100,000 inhabitants. In
      regions with few cases, lack of expertise may result in delay in diagnosis,
      improper treatment, and insufficient contact tracing. We suggest that
      tuberculosis is dealt with in one centre in each of the five regions in Denmark.
      LTOT is initiated and controlled by pulmonary specialists in 50% of cases only.
      Correct indication and follow up is better for patients who received LTOT by
      pulmonary specialists with a higher patient compliance. We conclude that LTOT
      should be centralised and treated by pulmonary specialists only.

PMID- 16640981
TI  - [Treatment centralization in health care. Percutaneous coronary intervention].

PMID- 16640982
TI  - [Centralised treatment of apoplexy is better].
AB  - Substantial evidence is established showing that centralising treatment and
      rehabilitation of stroke victims in stroke units reduces mortality and
      disability. Numbers needed to treat are 33 in order to avoid death of at least
      one patient and treat 20 to avoid disability of at least one patient. A Danish
      medical technology assessment indicates that stroke units are cost-beneficial.
      This knowledge has been available in Denmark for more than 15 years, but there is
      still not sufficient capacity to treat all stroke patients in stroke units.
      Hopefully, this problem will be resolved in the near future.

PMID- 16640983
TI  - [Centralised diagnostic].
AB  - Diagnostic examinations with complicated and expensive equipment should be
      centralised in departments of radiology, clinical physiology and nuclear
      medicine, clinical biochemistry etc. For the future reorganisation of hospitals
      in Denmark, focus on centralisation in larger university hospitals is recommended
      with close collaboration between diagnostic specialities and clinical
      specialities, and with research and advanced competence as main assets.

PMID- 16640988
TI  - [Renoprotection and blockade of the renin-angiotensin system: What shall we
      believe?].

PMID- 16640990
TI  - [ACE inhibitors and AT-II antagonists--do they protect against renal disease?].

PMID- 16640993
TI  - [Home blood pressure measurement in general practice: a comment!].

PMID- 16640994
TI  - [Most of the hospitalized patients with lung diseases are not correctly treated].

PMID- 16640996
TI  - [An editorial negligence].

PMID- 16640998
TI  - [The Chinese death camp Sujiatun].

PMID- 16641015
TI  - Expression of toll-like receptor 4 and 2 in horse lungs.
AB  - Toll-like receptor (TLR) is a key component in launching innate immune response
      to microbial challenge. TLR4 and TLR2 are recognized as specific receptors for
      components of Gram-negative and Gram-positive bacteria, respectively. Horses are
      extremely sensitive to endotoxin-induced cardiopulmonary distress and mortality
      which causes significant economic losses. To date, there are no data on the
      expression of TLR4 and TLR2 in horse lungs. Therefore, we examined the expression
      of TLR4 and TLR2 in lungs from normal or Escherichia coli lipopolysaccharide (E.
      coli LPS; 50 ng/kg; iv) treated horses. We also studied the impact of the
      depletion of pulmonary intravascular macrophages (PIM) on TLR4 and TLR2
      expression in normal or LPS-treated horses. RT-PCR showed TLR4 mRNA but not TLR2,
      in normal horse lungs. PIM depletion reduced TLR4 mRNA expression without
      affecting TLR2. The LPS treatment increased the expression of TLR4 and TLR2 mRNA
      in normal and PIM-depleted horses compared to normal saline-treated horses. Light
      and electron microscopic immunocytochemistry showed TLR4 protein in PIM, alveolar
      macrophages and septal endothelium in lungs from normal or LPS-treated horses.
      Immuno-gold electron microscopy showed TLR4 in PIM and dual-label immuno-electron
      microscopy co-localized TLR4 and LPS in the cytoplasm and nucleus of PIM of LPS
      treated horses. The present manuscript is the first report on the expression of
      TLR4 and TLR2 in normal and LPS-treated horses and direct co-localization of TLR4
      with LPS molecules in PIM. These data provide evidence that PIM are equipped with
      TLR4 to handle and rapidly respond to circulating endotoxins.

PMID- 16641016
TI  - Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the
      skin test for detection of paratuberculosis in United States Midwest sheep
      populations.
AB  - Our objective was to estimate the sensitivity and specificity of the agar-gel
      immunodiffusion test (AGID), the ELISA, and the skin test for the detection of
      Mycobacterium avium subspecies paratuberculosis (MAP) in sheep using Bayesian
      methods without a gold standard. Fourteen flocks (2 465 sheep) were used. Five
      flocks (450 sheep) were considered MAP non-infected and 9 flocks (2 015 sheep)
      had sheep infected with MAP. Sheep were skin tested and blood was collected for
      AGID and ELISA testing. Results were analyzed using a Bayesian 3-test in 1
      population model fitted in WinBUGS. The model allowed for dependence
      (correlation) between the two serologic tests, but these two tests were assumed
      to be conditionally independent of the skin test. The estimated specificity was
      99.5% (95% PI of 98.9-99.9%) for the AGID; 99.3% (98.4-99.8%) for the ELISA using
      an optical density measured cutoff of 0.20; 99.2% (98.1-99.8%) using a cutoff of
      0.15; 97.5% (95.8-98.7%) using a cutoff of 0.10; and 98.7% (97.3-99.5%) for the
      skin test. The estimated sensitivities were 8.3% (6.2-10.7%) for the AGID; 8.0%
      (6.0-10.4%), 10.6% (8.3-13.1%), and 16.3% (13.5-19.4%) for the ELISA using the
      cutoffs 0.20, 0.15, and 0.10 respectively; and 73.3% (62.3-85.8%) for the skin
      test. The skin test was specific in non-infected populations and sensitive in
      infected populations, although in some cases a positive skin test might represent
      MAP exposure rather than infection. The AGID and ELISA were specific but lacked
      sensitivity. The AGID and ELISA consistently identified two different populations
      of infected sheep with only moderate overlap between positive test results.

PMID- 16641017
TI  - Cat-scratch disease in veterinary-associated populations and in its cat reservoir
      in Taiwan.
AB  - In Taiwan, the first human case of cat-scratch disease (CSD) was diagnosed by a
      serologic test in 1998. Since then, no studies have been conducted to understand
      the epidemiology of the infection in Taiwan. Therefore, this study is the first
      epidemiologic survey of CSD in cats and humans in this country. Using veterinary
      associated individuals as the study population, it was identified that 1.7% of
      them were seropositive for B. henselae, and residence was the only factor
      associated with seropositivity. Bartonella species were successfully isolated
      from 25 (19.1%) of the 131 cats tested. Only B. henselae and B. clarridgeiae were
      obtained from bacteremic cats. Furthermore, 9.2% of 131 cats were dually-infected
      with genotypes I and II of B. henselae. It is the highest prevalence of co
      infection that has ever been reported worldwide. In cats, the seroprevalence was
      23.7% by indirect immunofluorescence antibody assay with B. henselae Houston-1
      (type I) as the antigen. When 12 bacteremic but seronegative cats were re-tested
      by IFA slides coated with B. henselae U-4 antigen (type II), 9 cats were
      identified to be seropositive. Our study further suggested that using only direct
      PCR of 16S-23S rRNA intergenic region or the combination of the PCR method and
      indirect immuno-fluorescence test will be useful to diagnose Bartonella-free
      cats.

PMID- 16641018
TI  - Characterisation of the lymph node immune response following Mycoplasma mycoides
      subsp. Mycoides SC infection in cattle.
AB  - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp.
      mycoides biotype Small Colony (MmmSC), is still a major cattle disease in Africa.
      Development of long-term protective vaccines, the only relevant strategy to
      achieve CBPP eradication, requires the characterisation of the protective immune
      mechanism. To this aim, the present study investigated the cellular immune
      response persisting in the lymph nodes of cattle infected naturally and
      experimentally by contact, one year post exposure. The lymph node cell
      composition, MmmSC responsiveness and phenotype of the MmmSC-responding
      lymphocytes were compared between animals according to the different outcomes of
      the infection. To unravel the protective mechanism, the study focussed on the
      MmmSC-specific memory immune response generated in recovered cattle, known to
      develop long-term immunity and to be resistant to reinfection. An MmmSC-specific
      immune response, mediated by IFNgamma-secreting CD4 T-cells, was detected in the
      lymph nodes of all recovered cattle. Furthermore, the magnitude of this immune
      response was significantly higher in animals with complete recovery than in
      recovered animals presenting lung sequestra. The findings suggest that, in
      recovered cattle, a subset of MmmSC-primed IFNgamma-secreting CD4 T-cells homed
      to the regional lymph nodes as MmmSC-specific memory T-cells, likely responsible
      for the protective anamnestic response. Induction and expansion of this subset of
      MmmSC-specific CD4 memory T-cells might be a major goal to develop efficient long
      term protective vaccines against CBPP.

PMID- 16641019
TI  - Reducing gaseous nitrogen loss from stored laying hen manure by the addition of
      carbohydrates.
AB  - Three separate experiments were conducted to determine if the addition of
      carbohydrate sources directly to freshly-produced laying hen manure reduced the
      loss of gaseous nitrogen containing compounds during 7 d of storage. The addition
      of sucrose (8 g/kg) to the manure resulted in a greater increase in bacterial
      numbers, a greater loss of carbon and a trend for a reduced loss of nitrogen.
      Although glucose addition to the manure increased bacterial numbers and tended to
      increase carbon loss, nitrogen loss increased relative to the control. Addition
      of straw to the manure did not affect the change in bacterial numbers or rate of
      nitrogen loss compared to the control treatment. Experiment 2 indicated that,
      when either sucrose or maltose were mixed (8 g/kg) with laying hen manure,
      microbial numbers were increased and gaseous nitrogen losses were reduced. A
      combination of starch plus alpha-amylase did not affect the characteristics of
      the manure. Experiment 3 showed that increasing sucrose addition gave a non
      linear reduction in nitrogen loss. Minimum nitrogen loss was obtained with 35
      g/kg sucrose, though the maximum increase in bacterial numbers occurred at 20
      g/kg of added sucrose.

PMID- 16641020
TI  - Corticosterone and fear behaviour in white and brown caged laying hens.
AB  - Physiological and behavioural measures of stress in caged hens on a commercial
      farm were compared between White Leghorn and brown Hyline strains, and between
      three tiers of cages. Blood and faecal samples were collected from undisturbed
      birds for corticosterone measurements. Plasma corticosterone responses to a
      stressor were measured by the collection of blood samples after 15, 30, and 60
      min of a handling stressor. Tonic immobility and novel object tests were used to
      measure fear behaviour. Plasma corticosterone in undisturbed hens and faecal
      corticosterone did not differ between White Leghorn and brown Hyline hens,
      whereas the plasma corticosterone response to a handling stressor was greater in
      White Leghorns. The duration of tonic immobility, latency to first head movement
      and number of head movements in tonic immobility tests were greater in white than
      brown birds, whereas the number of inductions was less for tonic immobility
      tests. There were no differences between the strains in their responses to a
      novel object. There were no differences between tiers in plasma corticosterone or
      corticosterone responses or tonic immobility responses, and no consistent
      differences in responses of birds to a novel object. This is the first study in
      which plasma and faecal corticosterone concentrations and fear behaviour have
      been measured together in laying hens, and the first description of plasma
      corticosterone responses to handling over 60 min for caged laying hens on a
      commercial farm. The study has shown the value of measuring endocrine and
      behavioural variables together to provide objective data on characteristics of
      different strains of hens.

PMID- 16641021
TI  - Behavioural responses to different floor space allowances in small groups of
      laying hens.
AB  - Under Council Directive 1999/74/EC, minimum space allowances per laying hen range
      from 550 cm(2) in unfurnished cages to 1111 cm(2) in alternative housing, and to
      40,000 cm(2) outdoors for free-range hens. In official reports on the welfare of
      laying hens, there is recognition that knowledge of their space requirements is
      inadequate. This experiment studied expression of behaviour, including spacing,
      in five groups of six and one group of five ISA Brown hens aged 21-33 weeks in an
      adjustable test pen providing 600, 2400, 4800, 7200, 9600, and 12,000 cm(2) floor
      area per hen. Each group was tested with every treatment. Home pens provided 2400
      cm(2) per hen. The main aim was to identify a hypothetical point at which mutual
      repulsion equals mutual attraction (a 'broken stick' response). Sequencing of
      treatments was according to a Latin square design, daytime tests lasted 2 h and
      had no feeder or drinker present, and overnight tests were done with 2400, 7200
      and 12,000 cm(2) per hen with a feeder and drinker present. Groups were video
      recorded from above to allow repeated measurements of spacing and other
      behaviours. In daytime tests, the relationship between mean distance to nearest
      neighbour and floor space allowance was asymptotic, rather than a 'broken stick'.
      The steepest part of the response was between 600 and 4800 cm(2) per hen. Changes
      in other behaviours were greatest between 600 and 2400 cm(2), and there was no
      significant change above 7200 cm(2). Spacing behaviour responses at night were
      the same as by day. It is concluded that any space allowance of less than about
      5000 cm(2) per hen imposes at least some constraint on free expression of
      behaviour, and that hens would benefit from any increase above the current
      minimum 1111 cm(2) usable area in alternative housing.

PMID- 16641022
TI  - Early-age housing temperature affects subsequent broiler chicken performance.
AB  - The influence of housing temperature in early life on subsequent growth and
      development of broiler chickens was investigated. Hatchlings were exposed to an
      ambient temperature of 34 degrees C (NT) or 28 degrees C (LT) on d 1. Both
      temperature regimes decreased with 1 degrees C per day for 5 d. At d 6 the
      ambient temperature of the LT group was increased to the same ambient temperature
      as the NT group. At d 29 all chickens were exposed to 10 degrees C for 7 d. Navel
      temperature was lower in the LT group than in the NT group from d 2 to 5. Body
      weight of the chickens was higher in the NT group than in the LT group and the
      difference between both groups increased in time. Temperature treatment during
      the early post-hatching period did not result in a long-term alternation in organ
      development, haematocrit value, energy and protein metabolism or the occurrence
      of ascites. Although not significantly, the course of metabolism suggested that
      early thermal treatment had long-term effects. Before cold treatment in week 5,
      the NT group showed higher values for energy and protein metabolism than the LT
      group, but during cold exposure, the opposite was found. We concluded that
      exposure of chickens to a moderate reduction in house temperatures during early
      post-hatching life seemed to have long-term negative effects on the performance
      of these chickens, but, on the other hand, it seemed that these chickens were
      better prepared to withstand cold challenge later in life.

PMID- 16641023
TI  - Influence of pop hole dimensions on the number of laying hens outside on the
      range.
AB  - The aim was to evaluate whether pop hole width is a factor influencing the number
      of laying hens on the range. Eight groups of 256 birds each were kept in 8
      compartments in a deep litter system. Hens could leave each compartment through
      two equally-sized pop holes arranged evenly along the side of each compartment.
      Pop hole dimensions were varied every second week in each compartment in a random
      order from 30, 60, 90, 120 up to 150 x 30 cm (width x height). Range per hen (10
      m(2)) were provided. The number of laying hens on range was counted hourly from
      07:00 to 20:00 h. Pop hole width did not significantly influence the number of
      laying hens on the range. Our findings show that, within the limits of the
      dimensions investigated, other factors are more important than pop hole
      dimensions.

PMID- 16641024
TI  - Effects of stocking density, flock size and management on the welfare of laying
      hens in single-tier aviaries.
AB  - Management practices, stocking rate and flock size may affect laying hen welfare
      but there have been few replicated studies in commercial non-cage systems that
      investigate this. This study used a broad range of physical and physiological
      indicators to assess the welfare of hens in 36 commercial flocks. Six laying
      period treatments were examined with each treatment replicated 6 times. It was
      not possible to randomly allocate treatments to houses, so treatment and house
      were largely confounded. Three stocking rates were compared: 7 birds/m(2) (n =
      2450), 9 birds/m(2) (n = 3150) and 12 birds/m(2) in either small (n = 2450) or
      large (n = 4200) flocks. In addition, at 12 birds/m(2), in both small and large
      flocks, birds were subjected to either standard (SM) or modified (MM) management.
      MM flocks had nipple drinkers and no nest-box lights. Bone strength, fracture
      incidence, heterophil:lymphocyte (H:L) ratio, live weight, organ weights, serum
      creatine, serum osmolality, muscle pH and faecal corticosterone were measured on
      samples of birds at the end of the rearing period and at the end of lay. During
      the laying period, mortality, production and integument condition were recorded
      at regular intervals. Birds housed at 9 birds/m(2) had higher mortality than
      birds housed at 12 birds/m(2) by the end of lay, but not higher than birds housed
      at 7 birds/m(2). Birds housed at 7 and 9 birds/m(2) had lower percent liver
      weight, and worse plumage condition than most of the 12 bird/m(2) treatments.
      Modified management tended to improve plumage condition. There were no clear
      effects of flock size on the welfare indicators recorded. At the end of the
      rearing period fracture incidence was almost negligible and H:L ratio was within
      a normal range. By the end of lay fracture incidence was 60% and H:L ratio was
      high, with no treatment effect for either measure. This, together with
      information on faecal corticosterone, feather loss and mortality, suggests that
      the welfare of birds in all treatments was relatively poor by the end of lay.

PMID- 16641025
TI  - Variance components for live weight, body measurements and reproductive traits of
      pair-mated ostrich females.
AB  - Estimates of genetic parameters for reproductive traits, live weight and body
      measurements were obtained using data from a pair-mated ostrich flock at
      Oudtshoorn in South Africa. Reproductive traits included total egg and chick
      production, along with hatchability percentage. Live weight, chest circumference
      and tail circumferences were recorded at the commencement and cessation of
      breeding. Heritability estimates (h(2)) were 0.23 for egg production, 0.20 for
      chick production, 0.10 for hatchability, 0.20 to 0.34 for live weight, 0.12 for
      chest circumference and 0.30 to 0.38 for tail circumference. Female permanent
      environmental effects (c(2)) amounted to 0.18 for egg production, 0.18 for chick
      production, 0.21 for hatchability, 0.32 to 0.36 for live weight and 0.23 to 0.32
      for chest circumference. Service sire exerted significant effects only on
      hatchability (0.22) and subsequently chick production (0.09). Genetic
      correlations of reproductive traits with live weight were low to moderate,
      variable in sign, and did not differ significantly from zero. Correlations
      between live weight recorded at the beginning and end of the breeding season were
      unity for additive genetic and permanent environmental effects. Egg and chick
      production were highly correlated genetically and phenotypically, with the
      genetic correlation exceeding the theoretical limit. In unconstrained analyses,
      hatchability was positively related to chick production, including at the service
      sire level. Selection gains in the current flock and future generations are
      likely. No significant adverse relationships were found between live weight, body
      measurements and reproductive traits.

PMID- 16641026
TI  - Effect of vitamin and trace mineral withdrawal from finisher diets on growth
      performance and immunocompetence of broiler chickens.
AB  - The present study was carried out to examine the effect of vitamin (V) or trace
      mineral (TM) mix removal from finisher diet (42-56 d of age) on performance and
      immunocompetence of broilers. The dietary treatments were: (1) the basal diet
      with no supplemental V or TM; (2) the basal diet fortified with V mix only; (3)
      the basal diet fortified with TM mix only; and (4) the basal diet fortified with
      V and TM mix. At 47 d, four birds from each replicate (20/treatment) were
      injected with Newcastle disease (ND) antigen and blood samples were collected
      just before and 9 d after immunisation. The results showed that V and TM mix
      withdrawal from finisher diet did not impair either weight gain or feed
      conversion efficiency from d 42 to 56. Feed intake was significantly increased
      when both mixes were omitted from the diet. Dietary treatments had no effect on
      carcase yield or proportion of breast and thigh meat and abdominal fat
      deposition. Packed cell volume (PCV) significantly decreased as a consequence of
      removal of V, TM and V+TM. Neither heterophil:lymphocyte ratio (H:L ratio),
      haemagglutination inhibition (HI) nor total antibody titre measured by ELISA were
      influenced by removal of V or TM supplements. In conclusion, the results from
      this study suggest that 14-d withdrawal of V or TM mix did not influence the
      immunocompetence of broilers.

PMID- 16641027
TI  - Bacterial shell contamination in the egg collection chains of different housing
      systems for laying hens.
AB  - The bacterial eggshell contamination of eating eggs in different commercial
      housing systems; two conventional cages, one organic aviary system and one barn
      production, were compared. The total counts of aerobic bacteria and the total
      counts of Gram-negative bacteria on the shell were used to detect key points
      where contamination occurred and to study the progress of contamination in the
      egg collection and transportation chains. The key points in the chain were those
      where eggs accumulated on a short conveyor belt, initial shell contamination in
      the alternative housing systems and extra nest-boxes placed on the ground. The
      high bacterial load of floor eggs (>6.3 log CFU total aerobic flora/eggshell)
      explains why they cannot be used for eating. On average higher initial shell
      contamination with total counts of aerobic bacteria was found for eggs from the
      alternative housing systems compared to the conventional systems; respectively
      5.46 compared to 5.08 log CFU/eggshell. However, initial contamination with total
      counts of Gram-negative bacteria on the shells was less in the alternative
      systems: 3.31 compared to 3.85 log CFU/shell. Initial bacterial shell
      contamination tended to correlate positively with the concentration of bacteria
      in the air of the poultry houses. Storing shell eggs, whether temporarily
      refrigerated or not, for 9 d or more, resulted in a decrease in bacterial
      eggshell contamination for both bacterial variables.

PMID- 16641028
TI  - Effects of dietary concentration and degree of polyunsaturation of dietary fat on
      endogenous synthesis and deposition of fatty acids in chickens.
AB  - Two experiments were performed to assess the effect of different amounts of
      dietary polyunsaturated fatty acids (PUFA) on fatty acid composition of chickens.
      The contribution of de novo fatty acid synthesis to fatty acid profile was also
      estimated. In trial 1, different fat sources were blended in different ratios
      allowing a gradient of dietary PUFA (from 15 to 61 g/kg), keeping added fat
      constant (9%). In trial 2, PUFA-rich oil was added at increasing inclusion rates
      (2, 4, 6 and 8%), achieving a dietary PUFA content ranging between 27 and 59
      g/kg. Increasing dietary PUFA inclusion resulted in an increase in PUFA
      deposition, with higher efficiency when dietary fat also provided saturated (SFA)
      and monounsaturated (MUFA) fatty acids (trial 1). Increasing dietary PUFA in both
      trials resulted in a decrease in SFA and MUFA concentration in the whole body.
      The estimated deposition of fatty acids from de novo synthesis was reduced when
      dietary fat content increased from 0 to 10%, varying between 35.34 and 17.66% for
      SFA and between 52.70 and 7.01% for MUFA in the whole body. The greater variation
      range for the MUFA supports the existence of a mechanism maintaining the SFA:
      (MUFA + PUFA) ratio within a specific range in biological membranes.

PMID- 16641029
TI  - Effects of increasing dietary concentrations of specific structured
      triacylglycerides on performance and nitrogen and energy metabolism in broiler
      chickens.
AB  - Specific structured triacylglycerides (STG) containing medium chain fatty acids
      in sn-1,3 positions and a long chain fatty acid in sn-2 position were prepared
      from rapeseed oil and capric acid (C10:0). A total of 80 female broiler chickens
      (Ross 208) were randomly allocated into five dietary treatments as two series of
      40 chicks: a basal diet with graded levels of STG of 0, 20, 40, 60 and 80 g/kg
      diet at the expense of rapeseed oil were fed to the chickens in groups of four.
      At 12 d of age the chickens were placed pair-wise in metabolism cages. The grower
      period (d 13-36) was divided into four consecutive balance periods each of 6 d.
      Two 24 h measurements of gas exchange in two open-air circuit respiration
      chambers were performed during the second and third day of each balance period.
      During the whole experiment there was a negative effect of the inclusion of STG
      on average feed intake. However, this only slightly affected average daily weight
      gain. Feed conversion efficiency improved linearly with the inclusion level of
      STG. Daily gain adjusted to mean daily feed intake increased linearly with
      inclusion rate of STG, indicating that the weight gain was affected by both feed
      intake and the enhancing effect on digestibility of STG. Weight of small
      intestine and colon decreased with increasing inclusion of STG. Utilisation of
      dietary protein relative to intake increased while that of retained fat tended to
      decrease resulting in a decreased utilisation of metabolisable energy (RE/ME) in
      birds receiving STG. Heat production (HE) was slightly lower in the STG groups.
      More of the dietary fat was oxidised when more STG was added, although the total
      amount of fat in the diets was kept constant.

PMID- 16641030
TI  - Valine requirements for immune and growth responses in broilers from 3 to 6 weeks
      of age.
AB  - Four experiments were conducted to evaluate valine (Val) requirements in Ross 508
      broilers from 3 to 6 weeks of age. Common diets were fed to broilers until 3
      weeks of age. Growth and carcass measurements were taken in all experiments.
      Immune responsiveness measurements were taken in Experiments 1 and 2. Birds given
      7.2 g Val/kg of diet in Experiment 1 had more abdominal fat than birds given 8.2
      g Val/kg of diet, but there were no differences in growth or other carcass
      measurements. Because growth performance was not reduced in birds given 7.2 g
      Val/kg of diet, Val concentration was reduced to 6.4 g Val/kg of diet in
      Experiments 2 and 3. Increasing Val from 6.4 to 8.7 g Val/kg of diet resulted in
      linear increases for BW gain, feed efficiency and Val intake in male birds, and
      Val intake in female birds. Quadratic responses to increasing dietary Val were
      not observed in any experiment. There were no effects of Val on innate or
      adaptive immunity. A nonessential amino acid mixture containing the same nitrogen
      content as the L-Val additions in Experiment 4 was added and tends to support the
      idea that the responses to Val were specific and not due to increases in total
      nitrogen. Dose responses to Val resulted in male, but not female, birds given 7.3
      g Val/kg of diet having improved BW gain and feed efficiency compared with birds
      receiving 6.4 g Val/kg of diet.

PMID- 16641031
TI  - Supplementation of the maternal diet with tomato powder and marigold extract:
      effects on the antioxidant system of the developing quail.
AB  - The effects of natural dietary carotenoid supplementation of the maternal diet
      (tomato powder and marigold extract) on transfer to the egg yolk and on the
      development of the antioxidant system of the young quail liver in early postnatal
      life were investigated. Sixty Japanese quail (Coturnix coturnix japonica) were
      allocated to four treatment groups, each with three replicates consisting of four
      females and one male each. The quail were fed on one of four different diets for
      23 d, each of them based on a low carotenoid, wheat/barley-based control diet.
      Tomato powder and marigold extract were added at rates of 20 and 2 g/kg to
      treatments 2 and 3, respectively. Marigold extract and tomato powder were also
      used in combination in treatment 4 at 2 g marigold + 20 g tomato powder/kg of
      diet. At 20 weeks of age, 60 eggs from each treatment were collected and placed
      in an incubator. After hatching, d-old quail from each group were reared (under
      standard commercial conditions) up to 14 d of age. They were fed on a low
      carotenoid commercial diet. After hatch, at 1, 7 and 14 d, the livers of five
      young quail from each treatment were assessed for total carotenoid concentration
      and carotenoid profile. Results indicated that lycopene is transferred from the
      feed to the egg yolk and further to the liver of the developing embryo. Elevated
      carotenoid concentration in the egg yolk and correspondingly in the liver of
      newly hatched quail remains significant during first week posthatch. Lutein and
      lycopene did not affect vitamin E concentration in the egg yolk or liver of the
      newly hatched quail. A combination of increased concentrations of lycopene and
      lutein in the egg yolk results in elevated concentrations of coenzyme Q in the
      liver of the newly hatched quail.

PMID- 16641032
TI  - Dietary arginine silicate inositol complex during the late laying period of quail
      at different environmental temperatures.
AB  - Arginine silicate inositol complex (ASIdagger; arginine 49.5%, silicon 8.2%,
      inositol 25%) is a novel material which is a bioavailable source of silicon and
      arginine. ASI offers potential benefits for vascular and bone health. Poor
      eggshell quality has been a major economic concern to commercial egg producers.
      Poor egg quality, skeletal abnormalities and architectural deterioration of bone
      tissue are common problems under hot conditions and in older birds. The effects
      of ASI supplementation on egg production, egg quality, levels of osteocalcin (OC)
      and bone mineral content were investigated in heat-stressed Japanese quail during
      the later part of the laying period. The birds were randomly assigned to six
      treatment groups consisting of six replicates of five birds each in a 2 x 3
      factorial arrangement of treatments (temperatures, ASI levels). The birds were
      kept in wire cages in a temperature-controlled room at either 22 degrees C (TN)
      or 34 degrees C (HS) for 8 h/d and fed either a basal (control) diet or the basal
      diet supplemented with either 500 or 1000 g of ASI/kg. Heat exposure reduced egg
      production, egg quality and bone mineralisation when the basal diet was fed. ASI
      supplementation had no effect on feed intake or egg production under TN or HS
      conditions. However, ASI supplementation increased egg weight, shell thickness,
      shell weight and Haugh unit in both TN and HS groups during the late laying
      period. Bone mineral density (BMD) was significantly improved by ASI
      supplementation in both TN and HS groups. Serum osteocalcin (OC) concentrations
      and alkaline phosphatase (ALP) activity increased linearly with dietary ASI
      supplementation during the late laying period. The amount of calcium and
      phosphorus in the excreta decreased, while ash, mineral content, calcium and
      phosphorus concentrations in tibia increased in ASI-supplemented quail in both TN
      and HS groups during the late laying period. ASI supplementation significantly
      improved egg quality and bone mineralisation in quail during the late laying
      period and did not affect feed consumption or egg production.

PMID- 16641033
TI  - Generation of hydroxyl radicals during ascites experimentally induced in
      broilers.
AB  - Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the
      most important features of the ascites syndrome in broiler chickens. However, the
      mechanism of cell injury causing the pathogenesis of the syndrome is not clearly
      understood. Our study aimed to examine the generation of hydroxyl radicals (OH*)
      in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens
      were purchased from a local hatchery and reared in an open poultry house for 46
      d. They were divided at random into three groups and ascites was induced in two
      groups by exposing them to low temperature or administration of triiodothyronine
      (T(3)). The third group served as control and was reared normally.
      Haematological, biochemical and pathological tests were used to determine the
      incidence of ascites: including total red blood cell (RBC), packed cell volume
      (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and
      ratio of right ventricular weight to total ventricular weight (RV/TV). A
      salicylate hydroxylation method was used to examine the generation of hydroxyl
      radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites,
      2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to
      detect the generation of OH*. An ascites syndrome was observed in T(3) and low
      temperature treated groups, as shown by necropsy changes and increases in f RBC,
      PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were
      increased in groups experiencing ascites compared to control group. It is
      suggested that reactive oxygen species that is OH* ions, may be involved in the
      pathogenesis of the ascites syndrome in broiler chickens.

PMID- 16641034
TI  - Evaluation of endothelial and inducible nitric oxide synthase mRNA expression in
      the lung of broiler chickens with developmental pulmonary hypertension due to
      cold stress.
AB  - To clarify the effect of cold-induced pulmonary hypertension on endothelial and
      inducible nitric oxide synthase (eNOS and iNOS) mRNA expression in the lung of
      broiler chickens, semi quantitative reverse transcription-PCR was performed on
      total RNAs isolated from lungs of the broiler chickens exposed to 5 weeks of cold
      stress. The eNOS gene was expressed increasingly with the increasing age during
      the rearing period. Comparing the treatment group with its related control group
      eNOS was expressed significantly only at d 21. Expression of iNOS mRNA also
      increased in both control and treatment groups with increasing age until d 28 and
      then decreased at d 35 and 42. Comparing the treatment group with its control
      group, iNOS mRNA level was significantly higher at 21 d of age in the cold
      exposed chickens. It was concluded that, although cold exposure could
      significantly increase eNOS and iNOS gene expression, cold-induced pulmonary
      hypertension is not associated with significant variations of eNOS and iNOS
      expression in the lungs of broiler chickens.

PMID- 16641035
TI  - Changes in pulmonary arteriole protein kinase calpha expression associated with
      supplemental L-arginine in broilers during cool temperature exposure.
AB  - The present study was conducted to examine the effect of supplemental L-arginine
      on pulmonary arteriole protein kinase Calpha (PKCalpha) expression in broilers
      exposed to cool temperature, to investigate further the molecular mechanisms of
      supplemental L-arginine on modulating pulmonary vascular functions in
      hypertensive broilers. Broilers were subjected to sub-thermoneutral (cool)
      temperature to induce pulmonary hypertension syndrome (PHS), and an additional 10
      g/kg L-arginine was added to the basal diet to evaluate the effects of
      supplemental L-arginine on PHS mortality, plasma nitric oxide (NO) production and
      pulmonary arterioles PKCalpha expression. Supplemental L-arginine reduced PHS
      mortality but did not affect right/total ventricle (RV/TV) ratios in clinically
      healthy birds. Birds fed additional L-arginine had increased plasma NO and
      decreased PKCalpha protein expression in pulmonary arterioles; NO production was
      negatively correlated with PKCalpha expression. These results demonstrated that
      supplemental L-arginine diminished PKCalpha expression in birds exposed to cool
      temperature. It is suggested that NO-induced loss of PKCalpha expression might be
      partially responsible for its effects on dilating pulmonary vasculature and
      inhibiting pulmonary vascular remodelling in vivo.

PMID- 16641039
TI  - Abstracts from VIII Swedish Heart Association meeting, Linkoping, Sweden, April
      26-28, 2006.

PMID- 16641036
TI  - Effects of phytoestrogens on testosterone secretion by Leydig cells from Bilgoraj
      ganders (Anser anser).
AB  - The aim of this study was to examine ganders at different stages of the
      reproductive season and the effect of: (1) diets with high phytoestrogen content
      and (2) in vitro phytoestrogen treatment on testosterone secretion by isolated
      Leydig cells. Thirty-six male Bilgoraj geese were fed control diets with low
      phytoestrogen content (containing grass meal) and diets with high phytoestrogens
      (containing alfalfa meal and soy). Testes were obtained from both groups of
      ganders at three different times of the breeding season: peak of reproductive
      activity (March), second half of reproductive activity (May) and beginning of
      photorefractoriness (July). Isolated Leydig cells were incubated with LH as well
      as genistein, daidzein, equol and coumestrol and the concentration of
      testosterone in the medium was determined by radioimmunoassay. The mean weight of
      testes from ganders in May and July decreased relative to their weights in March,
      but no significant differences among experimental groups were noted. No
      differences were observed in basal and LH-stimulated testosterone secretion by
      Leydig cells of ganders fed the control diets and the diets with higher
      phytoestrogen content. In July, LH did not stimulate testosterone secretion in
      either group. In vitro treatment with genistein, daidzein and equol (5 and 50
      microM) inhibited basal and LH-stimulated testosterone production by Leydig cells
      from both groups. Coumestrol (5 and 50 microM) inhibited basal testosterone
      secretion only in March in the control group. Dietary exposure to phytoestrogens
      had a slight effect on in vitro testicular secretion in ganders. In vitro
      treatment with phytoestrogen inhibited testosterone production by Leydig cells.
      Genistein showed the strongest effect and coumestrol had the weakest influence on
      testicular secretion.

PMID- 16641040
TI  - Accelerated atherosclerosis, arterial thromboembolism, and preventive strategies
      in systemic lupus erythematosus.
AB  - With improved disease survival, arterial thromboembolism has become an important
      cause of morbidity in patients with systemic lupus erythematosus (SLE). A number
      of conventional and non-conventional risk factors are associated with accelerated
      atherosclerosis. Regular surveillance and control of traditional risk factors is
      mandatory, and so is the appropriate use of the statins, anti-malarial agents,
      anti-platelet agents, and anti-coagulation for primary and secondary prevention
      of arterial thromboembolism in SLE patients. Judicious use of corticosteroids,
      calcineurin inhibitors, hormonal replacement therapy, and the cyclooxygenase 2
      inhibitors is equally important.

PMID- 16641041
TI  - Lower urinary tract symptoms in female patients with rheumatoid arthritis.
AB  - OBJECTIVE: Patients with autoimmune diseases such as systemic lupus erythematosus
      (SLE) and Sjogren's syndrome (SS) are associated with an increased severity of
      lower urinary tract symptoms (LUTS). Recent surveys also reveal that rheumatoid
      arthritis (RA) is prevalent in patients with interstitial cystitis (IC).
      Therefore, we have investigated LUTS in patients with RA. METHODS: A total of 198
      female patients with RA, aged 40 years or older, from the rheumatology outpatient
      clinic completed this prospective study. The American Urological Association
      Symptom Index (AUASI) score was used to assess the severity of LUTS and the
      O'Leary-Sant Symptom Index (ICSI) was used to evaluate IC-like urinary symptoms
      in these patients, which were compared to those of 679 age-matched controls. The
      possible associations of clinical parameters with LUTS were also explored.
      RESULTS: The Mean AUASI score and the percentage of individuals reporting severe
      LUTS (AUASI score > or = 20) or IC-like urinary symptoms (ICSI score > or = 12)
      showed no significant differences between the RA and control groups. However, in
      the RA group multivariate regression analyses identified patients with secondary
      SS (n = 21) to be associated with a significantly higher AUASI score (p = 0.007)
      and a higher percentage of severe LUTS (p = 0.02); these were also significantly
      higher than those of the control group (p = 0.02 and p = 0.01, respectively).
      CONCLUSION: Patients with RA have similar urinary complaints when compared to
      controls. However, those with secondary SS have a greater severity of LUTS, a
      finding similar to that observed in patients with primary SS.

PMID- 16641042
TI  - Drug survival and reasons for discontinuation of intramuscular methotrexate: a
      study of 212 consecutive patients switching from oral methotrexate.
AB  - OBJECTIVES: To assess the drug survival and reasons for discontinuation of
      intramuscular methotrexate (imMTX) in rheumatological patients who had switched
      to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive
      patients who switched from oMTX to imMTX therapy at our outpatient clinic between
      April 1997 and January 2004 were collected retrospectively through survey of case
      records. Data included reason for discontinuation of oMTX, disease activity
      parameters, duration of imMTX therapy, and, in patients who withdrew, the reason
      for discontinuation of imMTX. RESULTS: The main reasons for switching from oMTX
      to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months,
      114 patients (54%) were still receiving imMTX therapy, and their median serum C
      reactive protein (CRP) and the percentage of patients who had received
      glucocorticoids during the previous 6 weeks had decreased (p<0.001). The median
      survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per
      cent of the patients received imMTX for more than 24 months. Of the 212 patients,
      41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events,
      respectively. Of the patients who had stopped oMTX because of adverse events, 22%
      also withdrew from imMTX because of adverse events. CONCLUSION: Half of the
      patients benefited from switching from oral to intramuscular methotrexate for at
      least 6 months, but only a minority adhered to the treatment for years. Lack of
      efficacy was the most frequent reason for discontinuation, while adverse events
      were rare.

PMID- 16641043
TI  - Conversion towards an atherogenic lipid profile in rheumatoid arthritis patients
      during long-term infliximab therapy.
AB  - OBJECTIVES: To analyse the effects of infliximab infusions on serum levels of
      lipids in patients with rheumatoid arthritis (RA) treated for 2 years. METHODS:
      Fifty-two patients (41 females and 11 males) with RA undergoing infliximab
      treatment (3 mg/kg) were consecutively recruited into the study. The mean (+/-SD)
      age of the patients was 54.6+/-12.5 years and mean disease duration was 14.1+/
      8.6 years. Blood was sampled before infusion at baseline, and at 3, 6, 12, 18 and
      24 months. Forty-one of the patients were also treated with methotrexate, 13 with
      other disease-modifying anti-rheumatic drugs (DMARDs) and 28 with prednisolone
      (<10 mg daily). For comparison, lipid levels were followed for 2 years in 70
      consecutively included patients with early RA during treatment with conventional
      DMARDs. RESULTS: There was an initial increase in plasma levels of cholesterol,
      high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)
      cholesterol, and LDL/HDL and total/HDL cholesterol ratios. However, after 3
      months HDL-cholesterol decreased significantly, followed after 6 months by
      cholesterol and LDL-cholesterol. The LDL/HDL and total/HDL-cholesterol ratios
      remained significantly raised. HDL-cholesterol increased and the ratios improved
      in patients with early RA receiving conventional treatment. The changes over time
      differed significantly between the patient groups. CONCLUSION: During infliximab
      infusion a pro-atherogenic lipid profile developed despite reduced inflammatory
      activity. The long-term decrease in HDL-cholesterol was unexpected considering
      the known effects of tumour necrosis factor-alpha (TNFalpha).

PMID- 16641044
TI  - Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Hyperhomocysteinaemia is a factor related to the development of
      atherosclerosis in rheumatoid arthritis (RA). However, Hispanics with RA develop
      high rates of coronary disease; there are no studies about the frequency and
      factors related to high levels of homocysteine in Mexican patients. OBJECTIVE: To
      evaluate the prevalence and characteristics associated with hyperhomocysteinaemia
      in Mexican patients with RA. METHODS: One hundred and fifty-two patients with RA
      were compared with 153 controls. The assessment in RA included clinical
      characteristics, disease activity (RADAR), functioning (HAQ-Di and global
      functional status), comorbidity, and radiological damage. Laboratory
      determinations included total serum homocysteine (tHcy), erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and
      lipid profile. RESULTS: Median levels of homocysteine were higher in RA compared
      with controls (11.3 vs. 9.3, p<0.001). Twenty per cent of the patients with RA
      had hyperhomocysteinaemia (>15 micromol/L) compared with 6% in controls
      (p<0.001). There was statistical association between hyperhomocysteinaemia in RA
      with male gender (p<0.001), impairment in the global functional status (p =
      0.004), higher radiological damage (p = 0.001), and CRP (p = 0.04). There was no
      association with RADAR, HAQ-Di, or RF, methotrexate dose or duration of use. In
      the adjusted multivariate model, the two variables associated with higher risk
      for hyperhomocysteinaemia were male gender (OR = 4.2, 95% CI 2 to 12, p = 0.006)
      and higher radiological damage (III-IV) (OR = 3.4, 95% CI 1.3 to 9, p = 0.01).
      CONCLUSIONS: Our data show a high prevalence of hyperhomocysteinaemia in Mexican
      patients with RA. More effort is required to evaluate and treat earlier this
      coronary risk factor.

PMID- 16641045
TI  - The Rheumatoid Arthritis Quality of Life (RAQoL) for Sweden: adaptation and
      validation.
AB  - OBJECTIVE: To produce and evaluate the official Swedish language version of the
      Rheumatoid Arthritis Quality of Life instrument (RAQoL). METHODS: The UK RAQoL
      was translated into Swedish by a bilingual translation panel. A separate lay
      panel was conducted to consider the appropriateness and comprehensibility of the
      items in Swedish. Interviews were conducted with 15 Swedish RA patients to assess
      face and content validity. Responses to a postal survey were used to calculate
      reproducibility and construct validity. RESULTS: Few difficulties arose in the
      translation process and the new language version was well received by the lay
      panel and field-test participants. One hundred and sixty-five RA patients
      participated in the postal survey (69% female; mean age 62.7 years, SD 11.3, RA
      duration range 1-62 years). Cronbach's alpha for the Swedish RAQoL was 0.91 and
      test-retest reliability was 0.95, indicating that the instrument has adequate
      inter-relatedness of items and very low inherent random measurement error. A high
      correlation with the Health Assessment Questionnaire (HAQ) was observed; this was
      expected because RA has significant physical manifestations that are in turn a
      significant determinant of QoL. The Swedish RAQoL was able to distinguish between
      patients who differed according to their self-perceived RA severity, general
      health, and rating of their RA today, in addition to whether or not the patient
      was experiencing a flare of RA. CONCLUSIONS: The official Swedish RAQoL was well
      received by RA patients. The psychometric quality of the adapted questionnaire
      means that it is suitable for inclusion in clinical trials involving patients
      with RA.

PMID- 16641046
TI  - Killer cell immunoglobulin-like receptor gene's repertoire in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the role of the killer cell immunoglobulin-like
      receptor (KIR) gene's repertoire in the pathogenesis of rheumatoid arthritis (RA)
      in Taiwan. METHODS: KIR genotypes were determined in 122 patients with RA and 96
      healthy controls by the sequence-specific primer polymerase chain reaction (SSP
      PCR) method. Human leucocyte antigen (HLA)-C genotyping was also performed
      simultaneously in 72 patients and 66 controls by the SSP-PCR method. RESULTS: The
      total carriage frequency of KIR 2DS4 regardless of corresponding HLA-Cw4 was
      significantly increased in RA patients compared with controls [p<0.001, odds
      ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.4, Pc<0.01]. The total
      carriage frequency of KIR 2DL1 regardless of corresponding HLA-C also tended to
      be increased in RA patients (p<0.02, OR = 2.1, 95% CI = 1.2-3.9, Pc = not
      significant). The frequency of KIR 2DS4 with corresponding HLA-Cw4 was increased
      in RA patients in comparison with controls (p = 0.02, OR = 3.2, 95% CI = 1.1
      9.4). Moreover, the association of RA with KIR 2DS4 depended on the presence of
      the corresponding HLA-Cw4. CONCLUSIONS: KIR 2DS4 may be a risk factor for
      susceptibility to RA in Taiwan.

PMID- 16641047
TI  - Atherosclerosis in Asian Indians with systemic lupus erythematosus.
AB  - OBJECTIVES: Atherosclerosis has emerged as an important late complication of
      systemic lupus erythematosus (SLE). Asian Indians, as an ethnic group, are known
      to be metabolically predisposed to development of early atherosclerosis. No data
      on this aspect of SLE are available from Asia. This study was undertaken to find
      the frequency of atherosclerosis in Indian lupus patients and the factors
      affecting such an occurrence. METHODS: Carotid artery intimo-medial thickness
      (IMT) and plaque were used as markers of atherosclerosis. High-resolution B-mode
      ultrasonography was used to compare carotid IMT and plaque in 50 patients with
      SLE and 50 age- and sex-matched healthy controls. RESULTS: Patients with lupus
      (age 31.6+/-10.05, median 30.5 years; disease duration 52.3+/-36.7, median 46
      months) exhibited a significantly greater IMT than controls (0.417+/-0.07 vs.
      0.362+/-00.07 mm; p = 0.003). Carotid plaques were seen in seven (14%) cases.
      None of the control population had plaques (p = 0.006). On bivariate analysis,
      the IMT was significantly affected by age, systolic blood pressure (SBP), disease
      duration and menopausal status. On multivariate analysis, the only factor
      significantly affecting IMT was SBP. The Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) score was the
      sole factor found to significantly affect the occurrence of plaque. CONCLUSIONS:
      Asian Indian lupus patients in our study, despite being relatively young and with
      shorter disease duration, exhibited premature atherosclerosis in the form of
      significantly thicker intimo-media and plaque. The factors found to affect
      accelerated atherosclerosis in our cohort were age, SBP, disease duration,
      postmenopausal status and the SLICC/ACR score.

PMID- 16641048
TI  - Endothelin-1 serum levels correlate with MCP-1 but not with homocysteine plasma
      concentration in patients with systemic sclerosis.
AB  - OBJECTIVES: To determine whether homocysteine (Hcy) plasma levels are correlated
      with molecules indicative of endothelial cell and fibroblast activation,
      including endothelin-1 (ET-1) and monocyte chemoattractant protein-1 and -3 (MCP
      1, MCP-3), in patients with systemic sclerosis (SSc). METHODS: Eighty-two
      patients were enrolled in this study; the control group included 75 age- and sex
      matched subjects. Plasma Hcy was determined by high-performance liquid
      chromatography; folic acid, and vitamin B(12) plasma levels were determined by a
      chemiluminescence method. ET-1, MCP-1, and MCP-3 were determined by enzyme-linked
      immunosorbent assay (ELISA). Analysis of the 677C-->T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase
      chain reaction (PCR) and digestion with the enzyme HinfI. RESULTS: Hcy levels
      were lower in patients whereas ET-1 was significantly higher in patients and
      correlated with MCP-1. Stratification of the patients on the basis of Hcy levels
      was not associated with any statistical difference in the concentration of ET-1,
      MCP-1, and MCP-3. Patients with diffuse disease presented the highest levels of
      ET-1 and MCP-1. The distribution of the MTHFR genotypes was not different in
      patients and controls. CONCLUSIONS: In SSc, Hcy plasma concentration does not
      influence ET-1, MCP-1, or MCP-3 levels. On the contrary, ET-1, a marker of
      vascular activation, correlates with MCP-1, a chemokine involved in the fibrotic
      process of SSc.

PMID- 16641049
TI  - Hand radiology characteristics of patients carrying the T(303)M mutation in the
      gene for matrilin-3.
AB  - OBJECTIVE: To determine whether the recently described hand osteoarthritis (HOA)
      associated T(303)M mutation in the gene for matrilin-3 (MATN3) is associated with
      specific radiological changes on hand radiographs. METHOD: Standard hand
      radiographs from 26 HOA patients carrying the T(303)M missense mutation in the
      MATN3 gene (T(303)M patients) were compared with those from 52 HOA controls
      matched for sex, age, and clinical disease severity. Two blinded readers scored
      the radiographs, using the Verbruggen-Veys anatomical scoring system for the
      interphalangeal and metacarpophalangeal joints and the OARSI atlas scoring system
      for the first carpometacarpal (CMC1) joints. A scoring system based on the latter
      was used for the scaphoid-trapezoid-trapezoideum (STT) joints. RESULTS: No
      particular distinguishing features were found in the T(303)M patients and the
      prevalence of erosive and cystic changes was similar to the control group. As a
      group, however, the T(303)M patients had more severe thumb-base affection,
      particularly in the STT joint. Thus, definite radiological OA in both CMC1 and
      STT joints and higher STT scores compared with CMC1 were significantly more
      common in patients carrying the T(303)M mutation. Radiological scores for joint
      space narrowing (CMC1 and STT) and osteophytes (STT) were also significantly
      higher in the T(303)M patients. CONCLUSION: Patients carrying the T(303)M
      mutation in the gene for matrilin-3 express a form of HOA that is radiologically
      indistinguishable from idiopathic HOA in individual patients but they have more
      severe thumb-base involvement, particularly in the STT joint. This is the first
      described genetic mutation that is associated with a common form of
      osteoarthritis.

PMID- 16641050
TI  - Systemic vasculitis associated with Fasciola hepatica infection.
AB  - We report the case of a 50-year-old man who presented with systemic vasculitis
      associated with Fasciola hepatica infection. The patient presented with severe
      skin, kidney, spleen, ophthalmic, and neurological compromise. An immunological
      examination for primary vasculitis was negative and other infections were
      discounted by microbiological and serological analyses. The patient was treated
      with steroids without clinical response. The Fasciola hepatica infection was
      confirmed by the presence of specific immunoglobulin G (IgG) serum antibodies
      detected by a quantitative enzyme-linked immunosorbent assay (ELISA) with an
      optical density (OD) of 0.483 OD units (normal value<0.170 OD units) and a high
      titre complement fixation (1/80 dilution). The patient received treatment with
      triclabendazole and all symptoms and systemic manifestations resolved within
      weeks. Hence, this previously unreported vasculitis-associated infection, if
      identified opportunely, can be treated and cured.

PMID- 16641051
TI  - A large ulcer and cutaneous small-vessel vasculitis associated with syphilis
      infection.
AB  - Cutaneous vasculitis (CV) is a condition with cutaneous manifestations and
      possible systemic involvement. The causative factors or associated diseases are
      usually drugs, infection, collagen vascular disease, or malignancy. Syphilis as a
      cause of cutaneous vasculitis is rare. We report the case of a large cutaneous
      ulcer and small-vessel vasculitis associated with syphilis infection. We suggest
      that in apparently idiopathic CV or a chronic ulcer refractory to treatment,
      screening should be performed to detect any underlying infection such as
      syphilis. It is important to have a rapid and accurate diagnosis because the
      lesions are very contagious, but may be rapidly and completely cured by early
      administration of antibiotic treatment.

PMID- 16641052
TI  - Epstein-Barr virus-associated mononucleosis caused by weekly low-dose
      methotrexate therapy in a rheumatoid arthritis patient.

PMID- 16641053
TI  - The genetic contribution of CTLA-4 dimorphisms in promoter and exon 1 regions in
      Japanese patients with rheumatoid arthritis.

PMID- 16641054
TI  - Dysphagia associated with anti-PM-Scl antibodies in systemic lupus erythematosus.

PMID- 16641055
TI  - Musculoskeletal and neuropsychiatric manifestations are the main source of
      persisting affection and organ damage in a German population of patients with
      systemic lupus erythematosus.

PMID- 16641056
TI  - Placental cytokine expression and NF-kappaB activity in women with rheumatic
      diseases.

PMID- 16641057
TI  - Methylprednisolone pulse therapy by the Tune-Mendoza protocol in a child with
      severe Henoch-Schonlein nephritis.

PMID- 16641059
TI  - Where the boys are: sexual expectations and behaviour among young women on
      holiday.
AB  - The main objectives of this study were to examine relationships between vacation
      sex expectations and travelling companionship type (solo, paired, or group), and
      behavioural outcomes such as engaging in a relationship while on vacation,
      procuring condoms, and initiating condom use with vacation sex partners among
      tourist women in Costa Rica. A brief interview was used to assess
      sociodemographic characteristics, vacation sex expectations and relationships,
      casual sex variables, and alcohol use among a convenience sample of 128 single
      female tourists 18 years of age or older. Univariate and multivariate analysis
      were used to examine relationships among variables of interest. Women who
      travelled solo or with a single female companion and women who anticipated having
      sex on holiday were more likely than other tourist women to report one or more
      vacation relationships, to have procured condoms, and to have initiated condom
      use with a vacation sex partner. Women who engage in unanticipated vacation
      relationships may be at increased risk of participating in unsafe sex with a
      partner met on holiday due to lack of condom procurement and/or initiation of
      condom use. The findings point to the importance of public health efforts to
      educate women regarding safer sex precautions when travelling on holiday.

PMID- 16641060
TI  - Gender dynamics in the primary sexual relationships of young rural South African
      women and men.
AB  - A substantial body of South African research describes the importance of gender
      dynamics within sexual relationships as factors underlying HIV risk, yet we know
      little about these factors among young adults-a group at exceptionally high risk
      of infection. Our primary objective was to explore the ways that young adult men
      and women interpret and enact gender roles within their established primary
      partnerships, and how these dynamics influence sexual behaviour in relation to
      HIV risk. We employed script theory to frame our analysis of the dynamics of
      gender. Fifty students (25 women, 25 men) at secondary schools in a rural
      district of KwaZulu/Natal, South Africa completed in-depth interviews about
      sexual interactions with their primary partner. While many participants indicated
      that the standards of sexual conduct within relationships reflect dominant gender
      role norms, our findings indicate that there are important variations in these
      roles with some male and female respondents accepting and reinforcing the rights
      of women to determine the nature of sexual interactions. Efforts aimed at
      improving acceptance and adoption of alternative scripts for women and men may
      help to broaden young people's repertoire of HIV prevention options.

PMID- 16641061
TI  - Sex behaviour of male Japanese tourists in Bangkok, Thailand.
AB  - This paper explores why Japanese men engage in potentially risky commercial
      sexual behaviours while on holiday in Thailand. Semi-structured, in-depth
      interviews were conducted with 30 heterosexual male Japanese tourists, aged 19
      36, who paid for sex with Thai women. Study participants were recruited at
      guesthouses in Bangkok. Analysis revealed eight main factors that encourage
      participation in commercial sex: a sense of freedom and anonymity during "time
      out" spent travelling in a foreign country; a sense that there are permissive
      norms governing commercial sex in Thailand; the perceived sexual desirability of
      Thai women, a sense of economic and racial superiority relative to Thai women; a
      sense of loneliness or feeling in need of companionship; peer influence; the
      widespread availability of inexpensive sexual services in Thailand; and sexual
      desire or need. Findings indicate that Japanese male sexual conduct reflects
      individual drives while on holiday, in the context of interactions among Japanese
      peers, shaped by Thailand's socio-cultural environment.

PMID- 16641062
TI  - Misrepresentation on the Internet and in real life about sex and HIV: a study of
      Latino men who have sex with men.
AB  - Experiences of men who have internet sex with men were studied to determine the
      level of misrepresentation in real life and on the Internet of physical,
      relationship, sexual interests, and HIV status. An internet-based questionnaire
      in English and Spanish ($20 compensation) recruited 1,026 Latino MISM over 3
      weeks. Four 'fib' scales were created to measure misrepresentation by the
      respondent and to the respondent on the Internet and IRL. Overall, respondents
      rated being misrepresented to on the Internet significantly highest, followed by
      being misrepresented to IRL and misrepresenting themselves to others on the
      Internet, and misrepresenting themselves to others IRL lowest. For HIV status
      there were no differences between Internet and IRL misrepresentation by others
      and Internet and IRL misrepresentation by self, but a significant difference
      between HIV status misrepresentation by self and others. Misrepresenters were
      more likely to have had cybersex before meeting their last partner and to prefer
      cybersex, to be more sexually compulsive, and to speak and think more in Spanish.
      Social desirability considerations account for the higher misrepresentation on
      physical characteristics and sexual interests by others, and higher
      misrepresentation on the Internet. However, misrepresentation of HIV status was
      the lowest category and while it was misrepresented more often by others than
      self, there were no internet/IRL differences. Data suggest that HIV
      misrepresentation occurred for 20% of men and was lower than other forms of
      misrepresentation. Implications for HIV prevention are discussed, along with the
      concept of levels of accuracy in internet communications.

PMID- 16641063
TI  - 'It's in the nature of men': women's perception of risk for HIV/AIDS in Chiang
      Mai, Thailand.
AB  - The paper examines the context of women's risk for HIV by assessing men's and
      women's sexual behaviour, attitudes towards sex work, and perception of risk for
      HIV in the city of Chiang Mai, Thailand. The findings are based on data collected
      in the mid-1990s, at the height of the epidemic. A range of significant issues
      were highlighted by the men and women who participated in this study. First, some
      men continued to have unsafe sex with sex workers. Second, fear of HIV motivated
      men to seek out friends and acquaintances instead of sex workers for sexual
      encounters because they were considered 'safe' from infection. Third, women in
      this study were largely unaware of this expansion of the sexual network beyond
      the sex work itself. Lastly, women's sexuality was largely unrecognized in public
      health responses, or by the male and female participants, leaving them at risk
      for HIV.

PMID- 16641064
TI  - Sex and the Internet: gay men, risk reduction and serostatus.
AB  - Access to the Internet has increased dramatically over the past decade as has its
      use for meeting sexual partners (e-dating), particularly among gay men. Between
      June 2002 and January 2004, 128 gay/bisexual men living in London were
      interviewed one-to-one about their experience of e-dating, sexual risk and HIV
      prevention. The men were recruited both online (through the Internet) and offline
      (in clinics and the community); 32 men were HIV-positive, 59 HIV-negative, while
      13 had never had an HIV test. A key finding was that both identity as well as
      anonymity are vital to e-dating. Through a process of online filtering and sero
      sorting, HIV-positive men are able to meet other positive men for anal sex
      without condoms. While this does not present a risk of HIV transmission to an
      uninfected person it does have implications for the potential transmission of
      other STIs such as syphilis and LGV. Through e-dating, HIV-positive gay men can
      also avoid abuse, discrimination and sexual rejection. Our findings do not
      support the suggestion that the attraction of e-dating is that it affords
      absolute anonymity. We found that the gradual expression of identity is vital for
      e-dating among gay men. Internet-based HIV prevention campaigns need to take
      account of the different ways in which gay reflexively manage aspects of their
      identity online.

PMID- 16641065
TI  - Using diaries to measure parameters of transactional sex: an example from the
      Trans-Africa highway in Kenya.
AB  - Conventional methods of elicitation have severe limitations where sensitive
      information is being sought, resulting from both self-disclosure and recall bias.
      The use of diaries largely circumvents both of these problems. Four hundred and
      three female sex workers based on a section of the Trans-Africa Highway in Kenya
      completed standard diaries for consecutive 28-day periods. Variables measured
      included numbers and types of different clients, condom use, occupation of
      client, movement patterns and days of menses. Mean numbers of sexual partners,
      liaisons and sex acts and inter-relationships between the variables measured are
      analysed. The study affirms the value of diaries as an elicitation method for
      studying transactional sex in a resource-poor setting. Usable diaries were
      received from 70% of those who had agreed to participate in the study. The
      diaries yield detailed quantitative data that describe the characteristics and
      dynamics of transactional sex on a major highway in Africa and provide
      information that may be used to estimate HIV transmission rates.

PMID- 16641070
TI  - The health information national trends survey: research from the baseline.
AB  - The decades surrounding the turn of the millennium will be remembered as a time
      of extraordinary opportunity in cancer communication. In 1990, the number of age
      adjusted deaths due to cancer in the U.S. population began a slow steady decline
      after a century of disparaging increase. Reasons for this decline have been
      attributed to long-awaited successes in primary prevention, especially related to
      tobacco, and early detection for cervical, breast, prostate, and colorectal
      cancers, as well as advances in treatment. This was also a time of unparalleled
      change in the cancer communication environment. Scientific health discoveries
      escalated with the completion of the Human Genome project in 2003, and
      penetration of the Internet made health information available directly to
      consumers. To seize the opportunity afforded by these changes, the National
      Cancer Institute (NCI) launched the Health Information National Trends Survey
      (HINTS). Fielded for the first time in 2003, the HINTS is a nationally
      representative, general population survey of noninstitutionalized adults in the
      United States 18 years and older. This supplement contains a compilation of
      original research conducted using the data generated by the first administration
      of the HINTS telephone interviews. Covering topics in cancer knowledge, cancer
      cognition, risk perception, and information seeking, the articles represent an
      interdisciplinary view of cancer communication at the turn of the millennium and
      offer insight into the road ahead.

PMID- 16641071
TI  - Cancer knowledge and disparities in the information age.
AB  - Increasing information flow often leads to widening gaps in knowledge between
      different socioeconomic status (SES) groups as higher SES groups are more likely
      to acquire this new information at a faster rate than lower SES groups. These
      gaps in knowledge may offer a partial but robust explanation for differential
      risk behaviors and health disparities between different social groups. Drawing on
      the Health Information National Trends Survey (HINTS 2003), a national survey of
      communication behaviors conducted by the National Cancer Institute (NCI), we
      examine the relationship between publicity and knowledge gaps on two cancer
      topics that received different levels of publicity: knowledge about tobacco and
      sun exposure and their respective links to cancer. Analyses of the HINTS 2003
      data suggest that differential knowledge levels of causes of cancer between SES
      groups are one potential explanation of cancer disparities that have been
      extensively reported in the literature. It is evident that high income and high
      education are associated with awareness about causes of major cancers such as
      lung and skin, and may allow people to protect themselves and minimize their
      risks. The data also show that heavier media attention could attenuate the
      knowledge gaps though moderate publicity or lack of news coverage may actually
      widen them. Last, the findings in this article suggest that it is necessary to
      take into account the SES variation within different racial and ethnic groups
      rather than mask them by treating the groups as one.

PMID- 16641072
TI  - Knowledge of colon cancer screening in a national probability sample in the
      United States.
AB  - This study examined colon cancer screening knowledge and potential covariates
      (demographic, health, health care, and cancer information seeking) among adults
      of at least 45 years of age. Data were analyzed from the 2003 National Cancer
      Institute's (NCI's) Health Information National Trends Survey (HINTS 2003), a
      U.S. random-digit dial study. Our sample consisted of 3,131 adults (53.6% female,
      77.9% White). The colon cancer screening knowledge questions assessed whether
      participants had heard of the fecal occult blood test (FOBT; 73.7%), knew the
      recommended start age (26.1%), knew the frequency of FOBT (39.5%), had heard of
      flexible sigmoidoscopy or colonoscopy (84.3%), knew the start age (39.6%), and
      knew the frequency with which to test (12.8%). Factors associated with lower
      knowledge (all equal to p < .05 in a multivariate analysis) included being
      younger (45 to 49 years old) or older (70 years old or more), African American or
      non-Hispanic other, unmarried; had lower educational attainment; had not visited
      a health care provider in the past year; had not previously undergone FOBT; and
      had never looked for cancer information. This study documents low rates of colon
      cancer screening knowledge in the general population, and identifies subgroups
      where health communication interventions are most warranted.

PMID- 16641073
TI  - Absolute and comparative risk perceptions as predictors of cancer worry:
      moderating effects of gender and psychological distress.
AB  - Risk perceptions for cancer measured on absolute scales (e.g., "What is the
      likelihood that you will get cancer?") and on comparative scales (e.g., "How does
      your risk compare with that of someone similar to you?") are independently
      associated with worry about cancer. We examined this finding in a large sample
      across several types of cancer, and explored whether these relationships are
      moderated by three clinically relevant variables-gender, levels of psychological
      distress, and cancer experience. Participants were respondents in a national
      survey who reported risk perceptions and worry regarding colon cancer (923 men,
      1,532 women), breast cancer (2,154 women), and prostate cancer (860 men), and
      completed a validated measure of psychological distress. Analyses showed that
      absolute and comparative risk perceptions were independent predictors of worry
      across all cancer sites, but that absolute risk perceptions were significantly
      more predictive than comparative risk perceptions of worry for women (but not
      men). Among people who were more highly distressed, comparative risk perceptions
      were the only significant predictor of worry. Absolute risk and comparative risk
      were equally predictive of cancer worry among people who previously had been
      diagnosed with cancer. These findings imply that interventions highlighting the
      communication of comparative risk information may be differentially effective
      depending on the audience.

PMID- 16641074
TI  - Perceived ambiguity about cancer prevention recommendations: relationship to
      perceptions of cancer preventability, risk, and worry.
AB  - In this study, we apply the concept of "ambiguity," as developed in the decision
      theory literature, to an analysis of potential psychological consequences of
      uncertainty about cancer prevention recommendations. We used Health Information
      National Trends Survey (HINTS) 2003 data to examine how perceived ambiguity about
      cancer prevention recommendations relates to three other cognitive variables
      known to influence cancer-protective behavior: perceived cancer preventability,
      perceived cancer risk, and cancer-related worry. Using logistic regression
      analyses, we tested several predictions derived from a review of literature on
      the effects of ambiguity perceptions on decision making, cognitions, and
      emotions. We found perceived ambiguity to have a strong negative relationship
      with perceived cancer preventability, consistent with "ambiguity aversion"-a
      pessimistic bias in the interpretation of ambiguity. Cancer worry moderated this
      relationship; ambiguity aversion increased with higher levels of worry. At the
      same time, perceived ambiguity was positively related to both perceived cancer
      risk and cancer worry. Furthermore, perceived risk partially mediated the
      relationship between perceived ambiguity and worry. These findings suggest that
      perceived ambiguity about cancer prevention recommendations may have broad and
      important effects on other health cognitions. We discuss ethical implications of
      these findings for health communication efforts, and propose a tentative causal
      model to guide future research.

PMID- 16641075
TI  - Predictors of perceived risk for colon cancer in a national probability sample in
      the United States.
AB  - This study examines potential predictors of perceived risk for colon cancer in a
      U.S. sample of 2,949 individuals aged 45 and older with no colon cancer history.
      We examined perceived comparative risk for colon cancer as the outcome in ordinal
      regression analyses, and perceived absolute risk for colon cancer in linear
      regression analyses. Potential predictors included demographics, current risk
      behaviors, self-reported health, family and personal cancer history, emotion
      variables (colon cancer worry, general anxiety, and fear of positive screening
      findings), general cancer beliefs (causes, lack of preventability, information
      overload), and cancer information seeking. Those who had poorer self-reported
      health, a family cancer history, and increased colon cancer worry had higher
      perceived comparative and absolute colon cancer risk (all ps < .05). Those who
      were younger, interviewed in Spanish, had increased anxiety, and information
      overload had higher comparative risk; those with a personal history of cancer and
      fear that colon cancer screening would result in positive findings had higher
      absolute risk (all ps < .05). We determined that older individuals, those with
      risk factors, and those with good subjective health may not realize their colon
      cancer risk. Those distressed about colon cancer and who report cancer prevention
      information overload may require different messages.

PMID- 16641076
TI  - Unrealistic optimism in smokers: implications for smoking myth endorsement and
      self-protective motivation.
AB  - Although some optimists may be accurate in their positive beliefs about the
      future, others may be unrealistic-their optimism is misplaced. Research shows
      that some smokers exhibit unrealistic optimism by underestimating their relative
      chances of experiencing disease. An important question is whether such
      unrealistic optimism is associated with risk-related attitudes and behavior. We
      addressed this question by investigating if one's perceived risk of developing
      lung cancer, over and above one's objective risk, predicted acceptance of myths
      and other beliefs about smoking. Hierarchical regressions showed that those
      individuals who were unrealistically optimistic (i.e., whose perceived risk was
      less than their objective risk) were more likely to endorse beliefs that there is
      no risk of lung cancer if one only smokes for a few years and that getting lung
      cancer depends on one's genes. Unrealistic optimists were also more likely to
      believe that a greater number of lung cancer patients are cured, but they were
      less likely to identify smoking cessation/avoidance as a way to reduce cancer
      risk. Most importantly, unrealistic optimists were less likely to plan on
      quitting smoking. Taken together, these data suggest that in the smoking arena,
      unrealistic optimism is a potentially costly cognitive strategy.

PMID- 16641077
TI  - Lack of acknowledgment of fruit and vegetable recommendations among nonadherent
      individuals: associations with information processing and cancer cognitions.
AB  - Inadequate consumption of fruits and vegetables is regarded as an important
      behavioral risk factor for multiple types of cancer. Nevertheless, adherence with
      the National Cancer Institute (NCI) guidelines to eat between five and nine
      servings of fruits and vegetables per day is remarkably low. The current study
      explored the extent to which nonadherent respondents in a national survey (N =
      5,625) listed fruit and vegetable consumption as a method by which to decrease
      their own or others' cancer risk. We sought to determine whether respondents who
      listed fruit and vegetable consumption as a method by which to decrease their own
      or others' cancer risk (hereafter referred to as "listers") differed from
      respondents who did not list fruit and vegetable consumption as a method by which
      to decrease their own or others' cancer risk (hereafter referred to as)
      "nonlisters" on measures of information processing and cancer cognitions.
      Nonlisters were more likely than listers to seek out cancer information but less
      likely to trust the information. The two groups did not differ in the amount of
      attention they paid to such information. Listers had lower absolute risk
      perceptions than nonlisters, but listers and nonlisters did not differ on
      measures of relative breast and colon cancer risk perceptions and worry for
      cancer in general. Female listers did perceive themselves to be at less relative
      risk for breast cancer than nonlisters. Respondents were more likely to list
      fruit and vegetable consumption as a cancer-risk reduction strategy for others
      than for themselves, suggesting a "double standard" in their beliefs. These
      findings suggest that communications designed to promote fruit and vegetable
      consumption need to account for biases in how nonadherent individuals respond to
      these communications.

PMID- 16641078
TI  - Awareness of the National Cancer Institute's Cancer Information Service: results
      from the Health Information National Trends Survey (HINTS).
AB  - Established in 1975, the National Cancer Institute's (NCI's) Cancer Information
      Service (CIS) is a national information and education network that serves the
      nation by providing the latest scientific cancer information to the American
      public. The purpose of this study was to determine the public's awareness of the
      CIS and other national cancer and health organizations by analyzing data from the
      NCI's Health Information National Trends Survey (HINTS 2003). This study also
      examined sociodemographic, health, and communication correlates of awareness of
      CIS and other national health organizations: American Cancer Society (ACS),
      National Institutes of Health (NIH), and NCI. Results indicated that awareness of
      the CIS was low (32.8%). Some subgroups were more likely to be aware of the CIS
      than others. When comparing awareness levels of the four national health
      organizations, marked differences in patterns of awareness among specific
      subgroups emerged for many sociodemographic variables. For example, minority
      groups were significantly more aware of the CIS than Whites; however, for all
      three other organizations a greater percentage of Whites were aware of each
      organization. For the NIH, NCI, and ACS, respondents in the highest income group
      were most aware of each organization and, as income level increased awareness
      also increased. The CIS, respondents with the lowest income levels, however, were
      more aware of the CIS compared with middle- and high-income groups. A similar
      pattern was found for other sociodemographic variables. Results of this study
      will guide the development of a targeted promotional campaign for the CIS.

PMID- 16641079
TI  - Factors associated with patients' perceptions of health care providers'
      communication behavior.
AB  - We examined patients' ratings of communication with health care providers by
      sociodemographic characteristics, health care access, and health status. Data
      were from a national, population-based survey, the 2003 Health Information
      National Trends Survey (HINTS). The survey was administered to 6,369 adults from
      a representative sample of U.S. households. Linear regression analysis was
      conducted using SUDAAN. None of the sociodemographic variables were significantly
      associated with patients' ratings of providers' communication behavior in the
      linear model. Ratings of health care providers' communication behavior, however,
      were significantly higher among respondents with health insurance (p = 0.007) and
      those with a usual source of health care from whom they consistently sought care
      (p < 0.001). Ratings of provider communication were significantly lower among
      respondents who perceived their general health to be fair or poor (p < 0.001) and
      among those respondents with greater depressive symptoms (p < 0.001). Differences
      in patient ratings of health care providers' communication by health care access
      and health status suggest the potential for disparities in health outcomes.

PMID- 16641080
TI  - Cancer-related information seeking: hints from the 2003 Health Information
      National Trends Survey (HINTS).
AB  - Few nationally representative surveys have assessed the cancer-related
      information seeking behavior of the American public. Data for our analysis were
      from the 2003 Health Information National Trends Survey (HINTS). The goals of our
      analysis were to characterize cancer information seekers (3,011) and nonseekers
      (3,348) in terms of sociodemographic, health care access, and health status
      variables, and to describe the nature of the cancer-related information being
      sought by information seekers. Significant and independent associations with
      seeking status were identified for gender, age, race, income, education, personal
      and family history of cancer, and having a usual source of health care.
      Information seekers were less likely to be male (OR = .51); aged 65 or older (OR
      = .40); Hispanic (OR = .60); to have a usual source of health care (OR = .70);
      and more likely to have incomes greater than $50,000 (OR = 1.50), some college
      (OR = 1.87) or a college degree (OR = 2.95), a prior cancer diagnosis (OR =
      3.57), or a family history of cancer (OR = 2.17). Among cancer information
      seekers, the most frequently searched topic was cancer site-specific information
      (50.2%). Individuals who reported searching for cancer site-specific information
      were most frequently looking for information about breast cancer (23.8%),
      prostate cancer (11.5%), and skin cancer (11.3%). The HINTS survey provides a
      unique opportunity to explore the characteristics of information seekers and
      nonseekers and the content of information being sought by the public in a
      nationally representative sample; understanding gained from this effort provides
      generalizable and policy-relevant information about the American public's
      information needs.

PMID- 16641081
TI  - Cancer information scanning and seeking behavior is associated with knowledge,
      lifestyle choices, and screening.
AB  - Previous research on cancer information focused on active seeking, neglecting
      information gathered through routine media use or conversation ("scanning"). It
      is hypothesized that both scanning and active seeking influence knowledge,
      prevention, and screening decisions. This study uses Health Information National
      Trends Survey (HINTS, 2003) data to describe cancer-related scanning and seeking
      behavior (SSB) and assess its relationship with knowledge, lifestyle behavior,
      and screening. Scanning was operationalized as the amount of attention paid to
      health topics, and seeking was defined as looking for cancer information in the
      past year. The resulting typology included 41% low-scan/no-seekers; 30% high
      scan/no-seekers; 10% low-scan/seekers, and 19% high-scan/seekers. Both scanning
      and seeking were significantly associated with knowledge about cancer (B=.36;
      B=.34) and lifestyle choices that may prevent cancer (B=.15; B=.16) in
      multivariate analyses. Both scanning and seeking were associated with colonoscopy
      (OR = 1.38, for scanning and OR=1.44, for seeking) and with prostate cancer
      screening (OR=4.53, scanning; OR=10.01, seeking). Scanning was significantly
      associated with recent mammography (OR=1.46), but seeking was not. Individuals
      who scan or seek cancer information are those who acquire knowledge, adopt
      healthy lifestyle behaviors, and get screened for cancer. Causal claims about
      these associations await further research.

PMID- 16641082
TI  - Cancer information seeking preferences and experiences: disparities between Asian
      Americans and Whites in the Health Information National Trends Survey (HINTS).
AB  - Little is known about cancer information needs and seeking patterns in the
      rapidly growing Asian American population. The purpose of this study is to
      characterize cancer information seeking behaviors and preferences in Asian
      Americans and to examine their cancer-related knowledge and risk perceptions.
      Data from the nationally representative Health Information National Trends Survey
      (HINTS) database were analyzed to compare non-Hispanic Asians and Whites. Asians
      had lower awareness of the National Institutes of Health and American Cancer
      Society, were less likely to think that not smoking or quitting smoking would
      reduce cancer risk, were less knowledgeable about colon cancer screening, and
      considered their personal cancer risk to be low. Asians and Whites had similar
      media usage rates. They also had similar rates of preference for cancer
      information from various sources, although Asians were significantly more likely
      to prefer print materials. The level of trust of cancer information from doctors
      was high overall. This study is limited by under-representation of some
      demographic subpopulations, future surveys should oversample Asians and strive to
      include higher-risk Asians (e.g., elderly, poorly educated, immigrants, and those
      with limited English proficiency).

PMID- 16641083
TI  - Relationship of communication and information measures to colorectal cancer
      screening utilization: results from HINTS.
AB  - Utilization of colorectal cancer screening tests is suboptimal. Knowledge of
      colorectal cancer screening has been associated with completion of screening.
      Thus, increasing awareness of colorectal cancer screening may lead to significant
      improvements in screening rates. We assessed for the association among provider
      patient interaction, information-seeking patterns, sources of information, trust
      in cancer information, and Internet usage on colorectal cancer screening behavior
      using data obtained by the Health Information National Trends Survey (HINTS).
      From a cohort of 2,670 respondents greater than 50 years of age, we found that
      they (1) desired cancer information from personalized reading materials, meeting
      in person with a health care professional, and published materials; and (2) had
      great trust of information from their provider. Having trust in cancer
      information from the doctor or other health care professional was most predictive
      (OR 2.08, 95% CI 1.49-2.94) of being up to date. Other predictive factors include
      having a desire for cancer information from personalized reading materials (OR
      1.56, 95% CI 1.24-1.95) and using the Internet from home (OR 1.32, 95% CI 1.04
      1.67). We conclude that personalized communications from a health care provider
      are desired and trusted. Another promising information delivery approach is the
      Internet. Dedicated efforts using these approaches for information exchange may
      be most beneficial toward increasing utilization of colorectal cancer screening.

PMID- 16641084
TI  - A novel enzyme conferring streptothricin resistance alters the toxicity of
      streptothricin D from broad-spectrum to bacteria-specific.
AB  - Streptothricins (STs) produced by Streptomyces strains are broad-spectrum
      antibiotics. All STs consist of a carbamoylated D-gulosamine to which the beta
      lysine homopolymer (1 to 7 residues) and the amide form of the unusual amino acid
      streptolidine (streptolidine lactam) are attached. Although many ST-resistance
      genes have been identified in bacteria, including clinically isolated pathogens
      and ST-producing Streptomyces strains, only one resistance mechanism has been
      identified to date. This mechanism involves the modification of the ST molecule
      by monoacetylation of the moiety of the beta-lysine(s). In this study, we
      successfully isolated a novel ST-resistance gene (sttH) from Streptomyces
      albulus, which is a known ST nonproducer. The in vitro analysis of SttH
      demonstrated that this enzyme catalyzes the hydrolysis of the amide bond of
      streptolidine lactam, thereby conferring ST resistance. Interestingly, the
      selective toxicity of ST-D possessing 3x beta-lysine moiety was altered from
      broad-spectrum to bacteria-specific by the hydrolysis of streptolidine lactam,
      although ST-F (1 x beta-lysine) was detoxified by SttH in both prokaryotes and
      eukaryotes (yeasts). STs have not been clinically developed due to their
      toxicities; however, in this study, we showed that hydrolyzed ST-D (ST-D-acid)
      exhibits potent antibacterial activity even when its toxicity against eukaryotic
      cells is reduced by SttH. This suggests that ST-D-acid is a potential candidate
      for clinical development or for use as a new lead compound for drug discovery.

PMID- 16641085
TI  - Limited mutations in full-length tetrameric human alpha2-macroglobulin abrogate
      binding of platelet-derived growth factor-BB and transforming growth factor
      beta1.
AB  - alpha2-Macroglobulin (alpha2M) inhibits diverse extracellular proteases, binds
      growth factors such as platelet-derived growth factor-BB (PDGF-BB) and
      transforming growth factor-beta1 (TGF-beta1), and carries beta-amyloid peptide.
      alpha2M may also trigger cell signaling by binding to the low density lipoprotein
      receptor-related protein (LRP-1) and/or other cell surface receptors. Based on
      studies with recombinant alpha2M fragments expressed in bacteria and synthetic
      peptides, we previously localized a growth factor-binding site near the center of
      the alpha2M subunit. However, because intact alpha2M forms a hollow cylinder
      structure, an alternative model for growth factor binding involves nonspecific
      entrapment within the alpha2M core. To distinguish between these two models, we
      engineered mutations in the putative growth factor binding sequence of full
      length alpha2M. These mutations did not perturb the tetrameric structure of
      alpha2M, reaction with proteases, the thiol ester bonds, or binding to LRP-1. A
      single mutation (E730R) completely blocked binding of platelet-derived growth
      factor-BB to intact alpha2M. E730R did not alter TGF-beta1 binding; however, this
      mutation in combination with mutations at Glu714 and Asp719 eliminated the
      increase in TGF-beta1 binding associated with alpha2M conformational change.
      These studies demonstrate that growth factor binding to intact alpha2M is
      specific, involving a defined region of the alpha2M subunit. The exact sequences
      required for binding different growth factors may be non-identical, mimicking the
      model of the bait region in which different proteases target adjacent and
      sometimes overlapping sequences.

PMID- 16641086
TI  - An expanded WW domain recognition motif revealed by the interaction between Smad7
      and the E3 ubiquitin ligase Smurf2.
AB  - Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming
      growth factor-beta receptors and other targets. Recognition of the receptors by
      Smurf2 is accomplished through an intermediary protein, Smad7. Here we have
      demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7
      polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW
      domain binding site Trp, which interacts with target PY motifs, is a Phe in the
      Smurf2 WW3 domain. To examine this interaction, the solution structure of the
      complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3
      domain was determined. The structure reveals that, in addition to binding the PY
      motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail).
      Although the Phe in the WW3 domain binding site decreases affinity relative to
      the canonical Trp, this is balanced by additional interactions between the PY
      tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The interaction
      between the Smurf2 WW3 domain and the Smad7 PY motif is the first example of PY
      motif recognition by a WW domain with a Phe substituted for the binding site Trp.
      This unusual interaction allows the Smurf2 WW3 domain to recognize a subset of PY
      motif-containing proteins utilizing an expanded surface to provide specificity.

PMID- 16641087
TI  - DNA and RNA as new binding targets of green tea catechins.
AB  - The significance of catechins, the main constituent of green tea, is being
      increasingly recognized with regard to cancer prevention. Catechins have been
      studied for interactions with various proteins, but the mechanisms of the various
      catechins are not yet elucidated. Based on our previous observation that nucleic
      acids extracted from catechin-treated cells are colored, we studied whether
      catechins directly interact with nucleic acids using surface plasmon resonance
      assay (Biacore) and cold spray ionization-mass spectrometry. These two methods
      clearly showed that (-)-epigallocatechin gallate (EGCG) binds to both DNA and RNA
      molecules: the Biacore assay indicated that four catechins bound to DNA
      oligomers, and cold spray ionization-mass spectrometry analysis showed one to
      three EGCG molecules bound to single strand 18 mers of DNA and RNA. Moreover, one
      or two molecules of EGCG bound to double-stranded (AG-CT) oligomers of various
      nucleotide lengths. These results suggest that multiple binding sites of EGCG are
      present in DNA and RNA oligomers. Double-stranded DNA (dsDNA) oligomers were
      detected only as EGCG-bound forms at high temperature, whereas at low temperature
      both the free and bound forms were detected, suggesting that EGCG protects dsDNA
      oligomers from dsDNA melting to single-stranded DNA. Because both galloyl and
      catechol groups of EGCG are essential for DNA binding, both groups seem to hold
      strands of DNA via their branching structure. These findings reveal for the first
      time the link between catechins and polynucleotides and will intensify our
      understanding of the effects of catechins on DNA in terms of cancer prevention.

PMID- 16641088
TI  - Energetics of interaction between the G-protein chaperone, MeaB, and B12
      dependent methylmalonyl-CoA mutase.
AB  - MeaB is an auxiliary protein that supports the function of the radical B(12)
      dependent enzyme, methylmalonyl-CoA mutase, although its precise role is not
      understood. Mutations in the human homolog of MeaB, MMAA, lead to methylmalonic
      aciduria, an inborn error of metabolism that can be fatal. To obtain insights
      into the function of this recently discovered protein, we have characterized the
      entropic and enthalpic contributions to DeltaGdegree (assoc) for complexation of
      MeaB (in the presence and absence of nucleotides) with methylmalonyl-CoA mutase
      (in the presence and absence of cofactor). The dissociation constant for binding
      of methylmalonyl-CoA mutase and MeaB ranges from 34 +/- 4 to 524 +/- 66 nm,
      depending on the combination of nucleotide and mutase form. Holomutase binds MeaB
      15-fold more tightly when the nonhydrolyzable GTP analog, GMPPNP, is bound versus
      GDP. In contrast, the apomutase binds MeaB with similar affinity in the presence
      of either nucleotide. Our studies reveal that a large structural rearrangement
      accompanies interaction between these proteins and buries between approximately
      4000 and 8600A(2) of surface area, depending on the combination of ligands in the
      active sites of the two proteins. Furthermore, we demonstrate that MeaB binds GTP
      and GDP with similar affinity (K(d) of 7.3 +/- 1.9 and 6.2 +/- 0.7 microm,
      respectively at 20 degrees C) and has low intrinsic GTPase activity
      (approximately 0.04 min(-1) at 37 degrees C), which is stimulated approximately
      100-fold by methylmalonyl-CoA mutase. These studies provide insights into the
      energetics of interaction between the radical enzyme methylmalonyl-CoA mutase and
      MeaB, which are discussed.

PMID- 16641089
TI  - ADAMTS1 interacts with, cleaves, and modifies the extracellular location of the
      matrix inhibitor tissue factor pathway inhibitor-2.
AB  - ADAMTS1 is an extracellular metalloproteinase known to participate in a variety
      of biological processes that includes inflammation, angiogenesis, and development
      of the urogenital system. Many of its functions rely on its catalytic activity,
      which thus far has been limited to the cleavage of the matrix proteoglycans
      aggrecan and versican. However, it is likely that other substrates exist. Using a
      yeast two-hybrid screen, we identified the Kunitz-type inhibitor, tissue factor
      pathway inhibitor-2 (TFPI-2), as a binding partner of ADAMTS1. The interaction
      was confirmed by several biochemical and cell-based assays. In addition, our
      studies revealed alterations in the pattern of TFPI-2-secreted isoforms and in
      its extracellular location caused by the specific action of ADAMTS1.
      Interestingly, we found that TFPI-2 is a novel substrate of ADAMTS1. The cleavage
      removes a protease-sensitive C-terminal region in TFPI-2, altering its binding
      properties. The proposed role of TFPI-2 as a maintenance factor of extracellular
      remodeling suggests the indirect function of ADAMTS1 as an additional homeostatic
      player by its ability to alter the extracellular location of TFPI-2 and,
      therefore, to disrupt the remodeling machinery, a phenomenon directly associated
      to pathologies such as atherosclerosis and tumor progression.

PMID- 16641090
TI  - A G316A mutation of manganese lipoxygenase augments hydroperoxide isomerase
      activity: mechanism of biosynthesis of epoxyalcohols.
AB  - Lipoxygenases with R stereospecificity have a conserved Gly residue, whereas (S)
      lipoxygenases have an Ala residue. Site-directed mutagenesis has shown that these
      residues control position and S/R stereospecificity of oxygenation. Recombinant
      Mn-LO was expressed in Pichia pastoris, and its conserved Gly-316 residue was
      mutated to Ala, Ser, Val, and Thr. The G316A mutant was catalytically active. We
      compared the catalytic properties of Mn-LO and the G316A mutant with 17:3n-3,
      18:2n-6, 18:3n-3, and 19:3n-3 as substrates. Increasing the fatty acid chain
      length from C17 to C19 shifted the oxygenation by Mn-LO from the n-6 toward the n
      8 carbon. The G316A mutant increased the oxygenation at the n-8 carbon of 17:3n-3
      and at the n-10 carbon of the C17 and C18 fatty acids (from 1-2% to 7-11%). The
      most striking effect of the G316A mutant was a 2-, 7-, and 15-fold increase in
      transformation of the n-6 hydroperoxides of 19:3n-3, 18:3n-3, and 17:3n-3,
      respectively, to keto fatty acids and epoxyalcohols. The n-3 double bond was
      essential. An experiment under an oxygen-18 atmosphere showed that both oxygen
      atoms were retained in the epoxyalcohols. (R)-Hydroperoxides at n-6 of C17:3,
      18:3, and 19:3 were transformed 5 times faster than S stereoisomers. The G316A
      mutant converted (13R)-hydroperoxylinolenic acid to 13-ketolinolenic acid (with
      an apparent K(m) of 0.01 mm) and to epoxyalcohols (viz. erythro- and threo-11
      hydroxy-(12R,13R)-epoxy-(9Z,15Z)-octadecadienoic acids and one of the
      corresponding cis-epoxides as major products). A reducing lipoxygenase inhibitor
      stimulated the hydroperoxide isomerase activity, whereas a suicide-type
      lipoxygenase inhibitor reduced this activity. The n-3 double bond also appeared
      to influence the anaerobic formation of epoxyalcohols by Mn-LO, since 18:2n-6 and
      18:3n-3 yielded different profiles of epoxyalcohols. Our results suggest that the
      G316A mutant augmented the hydroperoxide isomerase activity by positioning the
      hydroperoxy group at the n-6 carbon of n-3 fatty acids closer to the reduced
      catalytic metal.

PMID- 16641091
TI  - Despite slow catalysis and confused substrate specificity, all ribulose
      bisphosphate carboxylases may be nearly perfectly optimized.
AB  - The cornerstone of autotrophy, the CO(2)-fixing enzyme, d-ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco), is hamstrung by slow catalysis and
      confusion between CO(2) and O(2) as substrates, an "abominably perplexing"
      puzzle, in Darwin's parlance. Here we argue that these characteristics stem from
      difficulty in binding the featureless CO(2) molecule, which forces specificity
      for the gaseous substrate to be determined largely or completely in the
      transition state. We hypothesize that natural selection for greater CO(2)/O(2)
      specificity, in response to reducing atmospheric CO(2):O(2) ratios, has resulted
      in a transition state for CO(2) addition in which the CO(2) moiety closely
      resembles a carboxylate group. This maximizes the structural difference between
      the transition states for carboxylation and the competing oxygenation, allowing
      better differentiation between them. However, increasing structural similarity
      between the carboxylation transition state and its carboxyketone product exposes
      the carboxyketone to the strong binding required to stabilize the transition
      state and causes the carboxyketone intermediate to bind so tightly that its
      cleavage to products is slowed. We assert that all Rubiscos may be nearly
      perfectly adapted to the differing CO(2), O(2), and thermal conditions in their
      subcellular environments, optimizing this compromise between CO(2)/O(2)
      specificity and the maximum rate of catalytic turnover. Our hypothesis explains
      the feeble rate enhancement displayed by Rubisco in processing the exogenously
      supplied carboxyketone intermediate, compared with its nonenzymatic hydrolysis,
      and the positive correlation between CO(2)/O(2) specificity and (12)C/(13)C
      fractionation. It further predicts that, because a more product-like transition
      state is more ordered (decreased entropy), the effectiveness of this strategy
      will deteriorate with increasing temperature.

PMID- 16641092
TI  - Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)
      miR155 transgenic mice.
AB  - MicroRNAs (miRNAs) represent a newly discovered class of posttranscriptional
      regulatory noncoding small RNAs that bind to targeted mRNAs and either block
      their translation or initiate their degradation. miRNA profiling of hematopoietic
      lineages in humans and mice showed that some miRNAs are differentially expressed
      during hematopoietic development, suggesting a role in hematopoietic cell
      differentiation. In addition, recent studies suggest the involvement of miRNAs in
      the initiation and progression of cancer. miR155 and BIC, its host gene, have
      been reported to accumulate in human B cell lymphomas, especially in diffuse
      large B cell lymphomas, Hodgkin lymphomas, and certain types of Burkitt
      lymphomas. Here, we show that E(mu)-mmu-miR155 transgenic mice exhibit initially
      a preleukemic pre-B cell proliferation evident in spleen and bone marrow,
      followed by frank B cell malignancy. These findings indicate that the role of
      miR155 is to induce polyclonal expansion, favoring the capture of secondary
      genetic changes for full transformation.

PMID- 16641093
TI  - A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk
      for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease.
AB  - Obesity and the associated pathologies including dyslipidemia, insulin
      resistance, type 2 diabetes, and cardiovascular disease constitute a major threat
      to global human health. Yet, the genetic factors that differentially predispose
      individuals to this cluster of pathologies are unclear. The fatty acid-binding
      protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and
      macrophages. Mice with aP2 deficiency are partially resistant to obesity-induced
      insulin resistance and type 2 diabetes, have lower circulating triglycerides, and
      exhibit marked protection against atherosclerosis. Here, we demonstrate a
      functionally significant genetic variation at the aP2 locus in humans that
      results in decreased adipose tissue aP2 expression due to alteration of the CAAT
      box/enhancer-binding protein binding and reduced transcriptional activity of the
      aP2 promoter. In population genetic studies with 7,899 participants, individuals
      that carry this T-87C polymorphism had lower serum triglyceride levels and
      significantly reduced risk for coronary heart disease and type 2 diabetes
      compared with subjects homozygous for the WT allele. Taken together, our results
      indicate that reduction in aP2 activity in humans generate a metabolically
      favorable phenotype that is similar to aP2 deficiency in experimental models.

PMID- 16641094
TI  - Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in
      aquaporin-2 that affects its phosphorylation and apical membrane accumulation.
AB  - Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation
      that causes severe hydronephrosis and obstructive nephropathy in affected mice.
      The mutation has been mapped to the distal end of mouse chromosome 15, but the
      mutated gene has not been found. Here, we describe the identification of a single
      base pair change in aquaporin-2 (Aqp2) in cph mutants through genetic linkage
      mapping. The C-T change led to the substitution of a Ser (S256) by a Leu in the
      cytoplasmic tail of the Aqp2 protein, preventing its phosphorylation at S256 and
      the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct
      principal cells. The interference with normal trafficking of Aqp2 by this
      mutation resulted in a severe urine concentration defect. cph homozygotes
      demonstrated polydipsia and produced a copious amount of hypotonic urine. The
      urine concentration defect could not be corrected by [deamino-Cys1,D-Arg8]
      vasopressin (DDAVP, a vasopressin analog), characteristic of nephrogenic diabetes
      insipidus. The nephrogenic diabetes insipidus symptoms and the absence of
      developmental defects in the pyeloureteral peristaltic machinery in the mutants
      before the onset of hydronephrosis suggest that the congenital obstructive
      nephropathy is most likely a result of the polyuria. This study has revealed the
      genetic basis for the classical cph mutation and has provided direct genetic
      evidence that S256 in Aqp2 is indispensable for the apical accumulation, but not
      the general glycosylation or membrane association, of Aqp2.

PMID- 16641095
TI  - Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine
      therapy for prevention of maternal-to-fetal HIV-1 transmission.
AB  - Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of
      HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency,
      duration, and clinical significance of this resistance is not well defined. We
      used a sensitive allele-specific PCR assay to assess the emergence and
      persistence of NVP-resistant variants in plasma samples from 22 women with HIV-1
      subtype C infection who participated in a study of sdNVP for prevention of mother
      to-child transmission of HIV-1. The women were categorized into three groups on
      the basis of detection of NVP resistance by standard genotype analysis. Group 1
      (n = 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo.
      Group 2 (n = 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n =
      7) had no NVP resistance detected at any time point. Allele-specific PCR analysis
      for the two most common NVP resistance mutations (K103N and Y181C) detected NVP
      resistant variants in most (16 of 21) samples that were negative for NVP
      resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after
      treatment. The frequency of NVP-resistant mutations decreased over time, but
      persisted above predose levels for more than 1 yr in > or = 23% of the women.
      These findings highlight the urgent need for studies assessing the impact of
      sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or
      other nonnucleoside reverse transcriptase inhibitors.

PMID- 16641096
TI  - A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus.
AB  - Homing of bone marrow (BM)-derived progenitors to the thymus is essential for T
      cell development. We have previously reported that two subpopulations of common
      lymphoid progenitors, CLP-1 and CLP-2, coexist in the BM and give rise to
      lymphocytes. We demonstrate that CLP-2 migrate to the thymus more efficiently
      than any other BM-derived progenitors. Short-term adoptive transfer experiments
      revealed that CLP-2 homing involves P-selectin/P-selectin glycoprotein ligand 1
      interactions, pertussis toxin-sensitive chemoattractant signaling by CC chemokine
      ligand 25 through CC chemokine receptor 9, and binding of the integrins
      alpha4beta1 and alphaLbeta2 to their respective ligands, vascular cell adhesion
      molecule 1 and intercellular adhesion molecule 1. Preferential thymus-tropism of
      CLP-2 correlated with higher chemokine receptor 9 expression than on other BM
      progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific
      and subset-selective multistep adhesion cascade.

PMID- 16641097
TI  - Wild rhesus monkeys generate causal inferences about possible and impossible
      physical transformations in the absence of experience.
AB  - Human infants and adults generate causal inferences about the physical world from
      observations of single, novel events, thereby violating Hume's thesis that
      spatiotemporal cooccurrence from prior experience drives causal perception in our
      species. Is this capacity unique or shared with other animals? We address this
      question by presenting the results of three experiments on free-ranging rhesus
      monkeys (Macaca mulatta), focusing specifically on their capacity to generate
      expectations about the nature of completely unfamiliar physical transformations.
      By using an expectancy violation looking-time method, each experiment presented
      subjects with either physically possible or impossible transformations of objects
      (e.g., a knife, as opposed to a glass of water, appears to cut an apple in half).
      In both experiments, subjects looked longer when the transformation was
      impossible than when it was possible. Follow up experiments ruled out that these
      patterns could be explained by association. These results show that in the
      absence of training or direct prior experience, rhesus monkeys generate causal
      inferences from single, novel events, using their knowledge of the physical world
      to guide such expectations.

PMID- 16641098
TI  - Human QKI, a potential regulator of mRNA expression of human oligodendrocyte
      related genes involved in schizophrenia.
AB  - The quaking viable mouse mutation (qk(v)) is a deletion including the 5'
      regulatory region of the quaking gene (Qki), which causes body tremor and severe
      dysmyelination in mouse. The function of the human quaking gene, called quaking
      homolog KH domain RNA-binding (mouse) (QKI), is not well known. We have
      previously shown that QKI is a new candidate gene for schizophrenia. Here we show
      that human QKI mRNA levels can account for a high proportion (47%) of normal
      interindividual mRNA expression variation (and covariation) of six
      oligodendrocyte-related genes (PLP1, MAG, MBP, TF, SOX10, and CDKN1B) in 55 human
      brain autopsy samples from individuals without psychiatric diagnoses. In
      addition, the tightly coexpressed myelin-related genes (PLP1, MAG, and TF) have
      decreased mRNA levels in 55 schizophrenic patients, as compared with 55 control
      individuals, and most of this difference (68-96%) can be explained by variation
      in the relative mRNA levels of QKI-7kb, the same QKI splice variant previously
      shown to be down-regulated in patients with schizophrenia. Taken together, our
      results suggest that QKI levels may regulate oligodendrocyte differentiation and
      maturation in human brain, in a similar way as in mouse. Moreover, we hypothesize
      that previously observed decreased activity of myelin-related genes in
      schizophrenia might be caused by disturbed QKI splicing.

PMID- 16641099
TI  - Observations on related ecological exponents.
AB  - We observe a relationship among three independently derived power laws in
      ecology: (i) total number of species versus area, (ii) species frequency versus
      species length, and (iii) maximal body size versus area. Aside from showing how
      these historically disparate phenomena are connected, we show how recent
      empirical results relating the maximal body size of top terrestrial vertebrates
      to the square root of land area conform to a prior theoretical expectation given
      by two of the above power laws. Of particular interest is the observation that
      the exponent relating species length to species frequency suggests a dimension
      for niche space for terrestrial vertebrate assemblages of D approximately 3/2.
      This value, along with power law for maximal body size, versus area, gives rise
      to the canonical species area exponent z approximately 1/4.

PMID- 16641100
TI  - Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation
      of aquaporin-2 phosphorylation at two sites.
AB  - Protein phosphorylation plays a key role in vasopressin signaling in the renal
      collecting duct. Large-scale identification and quantification of phosphorylation
      events triggered by vasopressin is desirable to gain a comprehensive systems
      level understanding of this process. We carried out phosphoproteomic analysis of
      rat inner medullary collecting duct cells by using a combination of
      phosphopeptide enrichment by immobilized metal affinity chromatography and
      phosphorylation site identification by liquid chromatography-mass spectrometry(n)
      neutral loss scanning. A total of 714 phosphorylation sites on 223 unique
      phosphoproteins were identified from inner medullary collecting duct samples
      treated short-term with either calyculin A or vasopressin. A number of proteins
      involved in cytoskeletal reorganization, vesicle trafficking, and transcriptional
      regulation were identified. Previously unidentified phosphorylation sites were
      found for membrane proteins essential to collecting duct physiology, including
      eight sites among aquaporin-2 (AQP2), aquaporin-4, and urea transporter isoforms
      A1 and A3. Through label-free quantification of phosphopeptides, we identified a
      number of proteins that significantly changed phosphorylation state in response
      to short-term vasopressin treatment: AQP2, Bclaf1, LRRC47, Rgl3, and SAFB2. In
      the presence of vasopressin, AQP2 monophosphorylated at S256 and diphosphorylated
      AQP2 (pS256/261) increased in abundance, whereas AQP2 monophosphorylated at S261
      decreased, raising the possibility that both sites are involved in vasopressin
      dependent AQP2 trafficking. This study reveals the practicality of liquid
      chromatography-mass spectrometry(n) neutral loss scanning for large-scale
      identification and quantification of protein phosphorylation in the analysis of
      cell signaling in a native mammalian system.

PMID- 16641101
TI  - In situ superexchange electron transfer through a single molecule: a rectifying
      effect.
AB  - An increasingly comprehensive body of literature is being devoted to single
      molecule bridge-mediated electronic nanojunctions, prompted by their prospective
      applications in molecular electronics and single-molecule analysis. These
      junctions may operate in gas phase or electrolyte solution (in situ). For
      biomolecules, the latter is much closer to their native environment. Convenient
      target molecules are aromatic molecules, peptides, oligonucleotides, transition
      metal complexes, and, broadly, molecules with repetitive units, for which the
      conducting orbitals are energetically well below electronic levels of the
      solvent. A key feature for these junctions is rectification in the current
      voltage relation. A common view is that asymmetric molecules or asymmetric links
      to the electrodes are needed to acquire rectification. However, as we show here,
      this requirement could be different in situ, where a structurally symmetric
      system can provide rectification because of the Debye screening of the electric
      field in the nanogap if the screening length is smaller than the bridge length.
      The Galvani potentials of each electrode can be varied independently and lead to
      a transistor effect. We explore this behavior for the superexchange mechanism of
      electron transport, appropriate for a wide class of molecules. We also include
      the effect of conformational fluctuations on the lowest unoccupied molecular
      orbital (LUMO) energy levels; that gives rise to non-Arrhenius temperature
      dependence of the conductance, affected by the molecule length. Our study offers
      an analytical formula for the current-voltage characteristics that demonstrates
      all these features. A detailed physical interpretation of the results is given
      with a discussion of reported experimental data.

PMID- 16641102
TI  - A plant-based oral vaccine to protect against systemic intoxication by Shiga
      toxin type 2.
AB  - Hemolytic uremic syndrome, the leading cause of kidney failure in children, often
      follows infection with enterohemorrhagic Escherichia coli and is mediated by the
      Shiga type toxins, particularly type 2 (Stx2), produced by such strains. The
      challenge in protecting against this life-threatening syndrome is to stimulate an
      immune response at the site of infection while also protecting against Shiga
      intoxication at distal sites such as the kidney. As one approach to meeting this
      challenge, we sought to develop and characterize a prototypic orally delivered,
      plant-based vaccine against Stx2, an AB5 toxin. First, we genetically inactivated
      the Stx2 active A subunit gene and then optimized both subunit genes for
      expression in plants. The toxoid genes were then transformed into the Nicotiana
      tabacum (tobacco) cell line NT-1 by Agrobacterium tumefaciens-mediated
      transformation. Toxoid expression was detected in NT-1 cell extracts, and the
      assembly of the holotoxoid was confirmed. Finally, mice were immunized by feeding
      with the toxoid-expressing NT-1 cells or by parenteral immunization followed by
      oral vaccination (prime-boost strategy). The immunized mice produced Stx2
      specific mucosal IgA and Stx2-neutralizing serum IgG. The protective efficacy of
      these responses was assessed by challenging the immunized mice with E. coli
      O91:H21 strain B2F1, an isolate that produces an activatable variant of Stx2
      (Stx2d) and is lethal to mice. The oral immunization fully protected mice from
      the challenge. Results of this study demonstrated that a plant-based oral vaccine
      can confer protection against lethal systemic intoxication.

PMID- 16641103
TI  - All possible modes of gene action are observed in a global comparison of gene
      expression in a maize F1 hybrid and its inbred parents.
AB  - Heterosis is the phenomenon whereby the progeny of particular inbred lines have
      enhanced agronomic performance relative to both parents. Although several
      hypotheses have been proposed to explain this fundamental biological phenomenon,
      the responsible molecular mechanisms have not been determined. The maize inbred
      lines B73 and Mo17 produce a heterotic F1 hybrid. Global patterns of gene
      expression were compared in seedlings of these three genotypes by using a
      microarray that contains 13,999 cDNAs. Using an estimated 15% false discovery
      rate as a cutoff, 1,367 ESTs (9.8%) were identified as being significantly
      differentially expressed among genotypes. All possible modes of gene action were
      observed, including additivity, high- and low-parent dominance, underdominance,
      and overdominance. The largest proportion of the ESTs (78%; 1,062 of 1,367)
      exhibited expression patterns that are not statistically distinguishable from
      additivity. Even so, 22% of the differentially regulated ESTs exhibited
      nonadditive modes of gene expression. Classified on the basis of significant
      pairwise comparisons of genotype means, 181 of these 305 nonadditive ESTs
      exhibited high-parent dominance and 23 exhibited low-parent dominance. In
      addition, 44 ESTs exhibited underdominance or overdominance. These findings are
      consistent with the hypothesis that multiple molecular mechanisms, including
      overdominance, contribute to heterosis.

PMID- 16641104
TI  - The pupal specifier broad directs progressive morphogenesis in a direct
      developing insect.
AB  - A key regulatory gene in metamorphosing (holometabolous) insect life histories is
      the transcription factor broad (br), which specifies pupal development. To
      determine the role of br in a direct-developing (hemimetabolous) insect that
      lacks a pupal stage, we cloned br from the milkweed bug, Oncopeltus fasciatus
      (Of'br). We find that, unlike metamorphosing insects, in which br expression is
      restricted to the larval-pupal transition, Of'br mRNA is expressed during
      embryonic development and is maintained at each nymphal molt but then disappears
      at the molt to the adult. Induction of a supernumerary nymphal stage with a
      juvenile hormone (JH) mimic prevented the disappearance of br mRNA. In contrast,
      induction of a precocious adult molt by application of precocene II to third
      stage nymphs caused a loss of br mRNA at the precocious adult molt. Thus, JH is
      necessary to maintain br expression during the nymphal stages. Injection of Of'br
      dsRNA into either early third- or fourth-stage nymphs caused a repetition of
      stage-specific pigmentation patterns and prevented the normal anisometric growth
      of the wing pads without affecting isometric growth or molting. Therefore, br is
      necessary for the mutable (heteromorphic) changes that occur during
      hemimetabolous development. Our results suggest that metamorphosis in insects
      arose as expression of br, which conveys competence for change, became restricted
      to one postembryonic instar. After this shift in br expression, the progressive
      changes that occur within the nymphal series in basal insects became compressed
      to the one short period of morphogenesis seen in the larva-to-pupa transition of
      holometabolous insects.

PMID- 16641105
TI  - Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide
      induces amphiregulin release and EGF receptor activation.
AB  - G protein-coupled receptors induce EGF receptor (EGFR) signaling, leading to the
      proliferation and invasion of cancer cells. Elucidation of the mechanism of EGFR
      activation by G protein-coupled receptors may identify new signaling paradigms. A
      gastrin-releasing peptide (GRP)/GRP receptor-mediated autocrine pathway was
      previously described in squamous cell carcinoma of head and neck. In the present
      study, we demonstrate that TNF-alpha converting enzyme (TACE), a disintegrin and
      metalloproteinse-17, undergoes a Src-dependent phosphorylation that regulates
      release of the EGFR ligand amphiregulin upon GRP treatment. Further investigation
      reveals the phosphatidylinositol 3-kinase (PI3-K) as the intermediate of c-Src
      and TACE, contributing to their association and TACE phosphorylation.
      Phosphoinositide-dependent kinase 1 (PDK1), a downstream target of PI3-K, has
      been identified as the previously undescribed kinase to directly phosphorylate
      TACE upon GRP treatment. These findings suggest a signaling cascade of GRP-Src
      PI3-K-PDK1-TACE-amphiregulin-EGFR with multiple points of interaction,
      translocation, and phosphorylation. Furthermore, knockdown of PDK1 augmented the
      antitumor effects of the EGFR inhibitor erlotinib, indicating PDK1 as a
      therapeutic target to improve the clinical response to EGFR inhibitors.

PMID- 16641106
TI  - Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice
      by mutation of Asp664.
AB  - The deficits characteristic of Alzheimer's disease (AD) are believed to result,
      at least in part, from the neurotoxic effects of beta-amyloid peptides, a set of
      39-43 amino acid fragments derived proteolytically from beta-amyloid precursor
      protein (APP). APP also is cleaved intracytoplasmically at Asp-664 to generate a
      second cytotoxic peptide, APP-C31, but whether this C-terminal processing of APP
      plays a role in the pathogenesis of AD is unknown. Therefore, we compared
      elements of the Alzheimer's phenotype in transgenic mice modeling AD with vs.
      without a functional Asp-664 caspase cleavage site. Surprisingly, whereas beta
      amyloid production and plaque formation were unaltered, synaptic loss,
      astrogliosis, dentate gyral atrophy, increased neuronal precursor proliferation,
      and behavioral abnormalities were completely prevented by a mutation at Asp-664.
      These results suggest that Asp-664 plays a critical role in the generation of
      Alzheimer-related pathophysiological and behavioral changes in human APP
      transgenic mice, possibly as a cleavage site or via protein-protein interactions.

PMID- 16641107
TI  - Substrate specificity of bacterial oligosaccharyltransferase suggests a common
      transfer mechanism for the bacterial and eukaryotic systems.
AB  - The PglB oligosaccharyltransferase (OTase) of Campylobacter jejuni can be
      functionally expressed in Escherichia coli, and its relaxed oligosaccharide
      substrate specificity allows the transfer of different glycans from the lipid
      carrier undecaprenyl pyrophosphate to an acceptor protein. To investigate the
      substrate specificity of PglB, we tested the transfer of a set of lipid-linked
      polysaccharides in E. coli and Salmonella enterica serovar Typhimurium. A hexose
      linked to the C-6 of the monosaccharide at the reducing end did not inhibit the
      transfer of the O antigen to the acceptor protein. However, PglB required an
      acetamido group at the C-2. A model for the mechanism of PglB involving this
      functional group was proposed. Previous experiments have shown that eukaryotic
      OTases have the same requirement, suggesting that eukaryotic and prokaryotic
      OTases catalyze the transfer of oligosaccharides by a conserved mechanism.
      Moreover, we demonstrated the functional transfer of the C. jejuni glycosylation
      system into S. enterica. The elucidation of the mechanism of action and the
      substrate specificity of PglB represents the foundation for engineering
      glycoproteins that will have an impact on biotechnology.

PMID- 16641108
TI  - The inverted chevron plot measured by NMR relaxation reveals a native-like
      unfolding intermediate in acyl-CoA binding protein.
AB  - The folding kinetics of bovine acyl-CoA binding protein was studied by 15N
      relaxation dispersion measurements under equilibrium conditions. Relaxation
      dispersion profiles were measured at several concentrations of guanidine
      hydrochloride (GuHCl). The unfolding rate constant (k(u)) was determined under
      conditions favoring folding, for which the folding rate constant (k(f)) dominates
      the relaxation in stopped-flow kinetic measurements. Conversely, k(f) was
      determined under conditions favoring unfolding, for which k(u) dominates stopped
      flow data. The rates determined by NMR therefore complement those from stopped
      flow kinetics and define an "inverted chevron" plot. The combination of NMR
      relaxation and stopped-flow kinetic measurements allowed determination of k(f)
      and k(u) in the range from 0.48 M GuHCl to 1.28 M GuHCl. Individually, the
      stopped-flow and NMR data fit two-state models for folding. However, although the
      values of k(f) determined by the two methods agree, the values of k(u) do not. As
      a result, a combined analysis of all data does not comply with a two-state model
      but indicates that an unfolding intermediate exists on the native side of the
      dominant energy barrier. The denaturant and temperature dependencies of the
      chemical shifts and k(u) indicate that the intermediate state is structurally
      similar to the native state. Equilibrium unfolding monitored by optical
      spectroscopy corroborate these conclusions. The temperature dependence of the
      chemical shifts identifies regions of the protein that are selectively
      destabilized in the intermediate. These results illustrate the power of combining
      stopped-flow kinetics and NMR spectroscopy to analyze protein folding.

PMID- 16641109
TI  - Kinetics and mechanism of electron transfer in intact photosystem II and in the
      isolated reaction center: pheophytin is the primary electron acceptor.
AB  - The mechanism and kinetics of electron transfer in isolated D1/D2-cyt(b559)
      photosystem (PS) II reaction centers (RCs) and in intact PSII cores have been
      studied by femtosecond transient absorption and kinetic compartment modeling. For
      intact PSII, a component of approximately 1.5 ps reflects the dominant energy
      trapping kinetics from the antenna by the RC. A 5.5-ps component reflects the
      apparent lifetime of primary charge separation, which is faster by a factor of 8
      12 than assumed so far. The 35-ps component represents the apparent lifetime of
      formation of a secondary radical pair, and the approximately 200-ps component
      represents the electron transfer to the Q(A) acceptor. In isolated RCs, the
      apparent lifetimes of primary and secondary charge separation are approximately 3
      and 11 ps, respectively. It is shown (i) that pheophytin is reduced in the first
      step, and (ii) that the rate constants of electron transfer in the RC are
      identical for PSII cores and for isolated RCs. We interpret the first electron
      transfer step as electron donation from the primary electron donor Chl(acc D1).
      Thus, this mechanism, suggested earlier for isolated RCs at cryogenic
      temperatures, is also operative in intact PSII cores and in isolated RCs at
      ambient temperature. The effective rate constant of primary electron transfer
      from the equilibrated RC* excited state is 170-180 ns(-1), and the rate constant
      of secondary electron transfer is 120-130 ns(-1).

PMID- 16641110
TI  - Delivery of care for adult patients with congenital heart disease in Europe:
      results from the Euro Heart Survey.
AB  - AIMS: The increasing number of adults with congenital heart disease (CHD) has
      prompted the development of recommendations for the management of these patients
      and for the organization of their healthcare. The aim of this report is to
      describe the delivery of care in Europe for adults with congenital cardiac
      anomalies. METHODS AND RESULTS: As part of the Euro Heart Survey on Adult
      Congenital Heart Disease, we obtained data from 71 voluntarily participating
      centres that detailed their care practices for these patients. Forty-eight of
      these centres were specialist centres and 23 were non-specialist centres. We
      found that only 19% of the specialist centres complied with defined standards for
      optimal care structure. The criteria that appeared to be most difficult for all
      centres to achieve were performing 50 congenital heart operations or more per
      year and involving nurse specialists in the care of these patients. CONCLUSION:
      This survey indicated that the provision of care in Europe for adults with
      congenital heart defects is suboptimal. To fully realize the benefits of cardiac
      surgery performed in infants and children, continuous effort must be applied by
      healthcare professionals in order to implement the recommendations on the
      organization of care for these patients.

PMID- 16641111
TI  - Constitutive expression of the pre-TCR enables development of mature T cells.
AB  - Expression and signalling through the pre-TCR and the TCRalphabeta resemble two
      critical checkpoints during T cell development. We investigated to which extent a
      pre-TCR can functionally replace mature TCRalpha chains during T cell
      development. For this purpose, transgenic mice were generated expressing the pre
      TCRalpha (pTalpha) under the transcriptional control of TCRbeta regulatory
      elements. We report here on the interesting finding that constitutive pTalpha
      expression allows complete T cell maturation. The pre-TCR complex permits a
      subset of beta-selected thymocytes to mature in the absence of TCRalpha into
      peripheral T cells (betaT cells) comprising up to 10% of all lymphocytes.
      Lymphopenia-driven proliferation of these betaT cells is similar to that of
      conventional alphabetaT cells. Furthermore, betaT cells proliferated and acquired
      effector function upon stimulation with allogeneic MHC.

PMID- 16641112
TI  - T cells to a dominant epitope of GAD65 express a public CDR3 motif.
AB  - Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes, and
      serve as a model for type 1 diabetes (T1D) and natural autoimmunity. T cell
      responses to the pancreatic islet antigen glutamic acid decarboxylase 65 (GAD65)
      can be detected in the spleens of young prediabetic NOD mice, which display a
      unique MHC class II molecule. Here, we report that a distinct TcR beta chain and
      CDR3 motif are utilized by all NOD mice in response to a dominant determinant on
      GAD65, establishing a public repertoire in the spontaneous autoimmunity to an
      important islet cell antigen. GAD65 530-543 (p530)-reactive T cells
      preferentially utilize the Vbeta4, Dbeta2.1 and Jbeta2.7 gene segments, with a
      CDR3 that is characterized by a triad of amino acids, DWG, preceded by a polar
      residue. In addition, we used CDR3 length spectratyping, CDR3-specific reverse
      transcriptase-PCR and direct TcR sequencing to show that the TcR beta chain
      structural patterns associated with p530-specific T cells consistently appeared
      in the islets of young NOD mice with insulitis, but not in the inflamed islets of
      streptozotocin-treated C57BL/6 mice, or in inflamed NOD salivary glands. To our
      knowledge, this is the first report to demonstrate that a public T cell
      repertoire is used in spontaneous autoimmunity to a dominant self-determinant.
      These findings suggest that defined clonotypes and repertoires may be
      preferentially selected in haplotypes predisposed to spontaneous autoimmunity.

PMID- 16641113
TI  - Plasmodium falciparum infection dynamics and transmission potential following
      treatment with sulfadoxine-pyrimethamine.
AB  - OBJECTIVES: To investigate the overall efficacy of sulfadoxine-pyrimethamine (SP)
      treatment and the corresponding transmission potential for patients infected with
      SP-resistant Plasmodium falciparum. METHODS: A mathematical model of the in-host
      dynamics of P. falciparum infections was used to simulate infections with
      parasites having different numbers of mutations in the dhfr and dhps genes and
      their responses to SP treatment. The treatment outcome and transmission potential
      of each simulated infection following SP treatment was assessed by tracking
      asexual parasite density and the number of days with sufficient mature
      gametocytes to give a > 95% probability of infecting a mosquito. RESULTS: The
      results show treatment failure only occurring in patients infected with parasites
      having two mutations in dihydrofolate reductase (DHFR) combined with at least two
      mutations in dihydropteroate synthetase (DHPS) or with parasites having a triple
      mutation in DHFR. Highly mutated parasites (three mutations in each gene) caused
      the highest clinical failure rate, while moderately mutated parasites (three
      mutations in DHFR plus one mutation in DHPS) produced a high rate of asymptomatic
      parasitological failure following SP treatment. This high rate of asymptomatic
      recrudescence caused the transmission potential of infections with moderately
      resistant parasites to exceed that of highly resistant parasites. CONCLUSIONS:
      The model output suggests that infection dynamics following SP treatment and the
      overall transmission potential are inherently linked. The combination of
      prolonged asymptomatic parasitaemia and increased transmission potential allows
      parasites having three mutations in DHFR, but fewer mutations in DHPS, to expand
      largely unnoticed.

PMID- 16641114
TI  - A multiplex PCR for beta-lactamase genes of Haemophilus influenzae and
      description of a new blaTEM promoter variant.
AB  - OBJECTIVES: To establish a multiplex PCR to detect and differentiate the beta
      lactamase genes of Haemophilus influenzae. METHODS: A collection of H. influenzae
      isolates with a range of different beta-lactamase genes were tested in parallel
      with individual PCRs and the multiplex assay developed in this study. RESULTS:
      The multiplex method was found to be superior to previous methods and was able to
      correctly detect and differentiate blaROB-1 and the variants of blaTEM present in
      the strains tested, including a previously unrecognized variant associated with a
      54 bp insertion in the promoter region. CONCLUSIONS: The multiplex PCR will be a
      useful tool for the surveillance of beta-lactamase genes in H. influenzae.

PMID- 16641116
TI  - Comment on: pharmacokinetics of inhaled colistin in patients with cystic
      fibrosis.

PMID- 16641117
TI  - Comparison of four methods for detection of teicoplanin resistance in methicillin
      resistant Staphylococcus aureus.
AB  - OBJECTIVES: To determine which method of determining the MIC of teicoplanin
      produces a result closely related to outcome in the critically ill patient.
      METHODS: Four methods of teicoplanin susceptibility testing-disc diffusion,
      Etest, VITEK (Legacy and VITEK 2) and agar incorporation-were compared for 47
      methicillin-resistant Staphylococcus aureus (MRSA) isolates from invasive
      intensive care unit (ICU) infections and 83 isolates from ICU patients colonized
      with the organism. Clinical outcome was recorded prospectively for all the
      patients. Another 13 reference laboratory strains of MRSA with reduced
      susceptibility to teicoplanin were tested. RESULTS: Both VITEK systems failed to
      demonstrate resistance in the three isolates identified as resistant by Etest or
      agar incorporation, and disc testing detected only one resistant isolate. A
      higher MIC, as found by Etest or agar incorporation, was associated with lower
      survival (n = 130, 95% CI -0.082 to -0.006, P = 0.023, Etest; n = 130, 95% CI 
      0.156 to -0.020, P = 0.011, agar). The findings for the 13 reference strains were
      similar, with a > or = 4-fold reduction in MIC between agar incorporation or
      Etest and VITEK2 for six isolates. CONCLUSIONS: Neither disc diffusion nor the
      VITEK systems are reliable for detection of teicoplanin resistance in MRSA. Etest
      and agar incorporation remain the methods of choice.

PMID- 16641118
TI  - Potential for organ donation in the United Kingdom: audit of intensive care
      records.
AB  - OBJECTIVES: To determine the true potential for solid organ donation from
      deceased heartbeating donors and the reasons for non-donation from potential
      donors. DESIGN: An audit of all deaths in intensive care units, 1 April 2003 to
      31 March 2005. The study was hierarchic, in that information was sought on
      whether or not brain stem testing was carried out; if so, whether or not organ
      donation was considered; if so whether or not the next of kin were approached; if
      so, whether or not consent was given; if so, whether or not organ donation took
      place. SETTING: 341 intensive care units in 284 hospitals in the United Kingdom.
      PARTICIPANTS: 46,801 dead patients, leading to 2740 potential heartbeating solid
      organ donors and 1244 actual donors. MAIN OUTCOME MEASURES: Proportion of
      potential deceased heartbeating donors considered for organ donation, proportion
      of families who denied consent, and proportion of potential donors who became
      organ donors. RESULTS: Over the two years of the study, 41% of the families of
      potential donors denied consent. The refusal rate for families of potential
      donors from ethnic minorities was twice that for white potential donors, but the
      age and sex of the potential donor did not affect the refusal rate. In 15% of
      families of potential donors there was no record of the next of kin being
      approached for permission for organ donation. CONCLUSIONS: Intensive care units
      are extremely good in considering possible organ donation from suitable patients.
      The biggest obstacle to improving the organ donation rate is the high proportion
      of relatives who deny consent.

PMID- 16641119
TI  - Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide
      exchange parameters.
AB  - It is a well-known fact that smoking is associated with a reduction in exhaled
      nitric oxide (NO) levels. There is, however, limited knowledge relating to the
      smoking-induced changes in production or exchange of NO in different compartments
      of the airways. This study comprised 221 adult subjects from the European
      Community Respiratory Health Survey II, who were investigated in terms of their
      exhaled NO, lung function, immunoglobulin E sensitisation and smoking habits. The
      following parameters were determined using extended NO analysis: airway tissue
      nitric oxide concentration (Caw,NO), airway transfer factor (or diffusing
      capacity) for nitric oxide (Daw,NO), alveolar nitric oxide concentration (CA,NO)
      and fractional exhaled nitric oxide concentration at a flow rate of 50 mL x s(-1)
      (FeNO,0.05). Maximum total airway nitric oxide flux (J'aw,NO) was calculated from
      Daw,NO(Caw,NO-CA,NO). Current smokers (n = 35) exhibited lower (geometric mean)
      FeNO,0.05 (14.0 versus 22.8 ppb), Caw,NO (79.0 ;versus 126 ppb) and J'aw,NO (688
      versus 1,153 pL x s(-1)) than never-smokers (n = 111). Ex-smokers (n = 75) were
      characterised by lower FeNO,0.05 (17.7 versus 22.8 ppb) and Jaw,NO (858 versus
      1,153 pL x s(-1)) than never-smokers. These relationships were maintained after
      adjusting for potential confounders (sex, age, height, immunoglobulin E
      sensitisation and forced expiratory volume in one second), and, in this analysis,
      a negative association was found between current smoking and CA,NO. Snus (oral
      moist snuff) consumption (n = 21) in ex-smokers was associated with an increase
      in Daw,NO and a reduction in Caw,NO, after adjusting for potential confounders.
      Passive smoking was associated with a higher CA,NO. Using extended nitric oxide
      analysis, it was possible to attribute the reduction in exhaled nitric oxide
      levels seen in ex- and current smokers to a lower total airway nitric oxide flux
      in ex-smokers and reduced airway and alveolar nitric oxide concentrations in
      current smokers. The association between snus (oral tobacco) use and reduced
      nitric oxide concentrations in the airways and increased nitric oxide transfer
      from the airways warrants further studies.

PMID- 16641120
TI  - Increased incidence of coronary artery disease in sleep apnoea: a long-term
      follow-up.
AB  - An increased incidence of cardiovascular disease has previously been reported in
      middle-aged males during a follow-up period of 7 yrs. The aim of the present
      study was to address the incidence of coronary artery disease (CAD) in a larger
      sample without any heart disease at baseline. The population comprised 308
      snorers (245 males and 63 females) with a mean +/- sd age of 49.0 +/- 9.9 yrs in
      1991. Data were collected via the Swedish Hospital Discharge Register, National
      Cause of Death Registry, clinical charts and questionnaires. Over 7 yrs, CAD was
      observed in 17 (16.2%) of 105 patients with obstructive sleep apnoea (OSA;
      overnight (6 h) oxygen desaturations > or =30 events) compared with 11 (5.4%) of
      203 snorers without OSA. OSA diagnosis at baseline was associated with an
      increased risk of development of CAD in a multivariate model. In the OSA group,
      CAD was confirmed in 16 (24.6%) of 65 incompletely treated patients compared with
      one (3.9%) of 26 efficiently treated subjects. Efficient treatment of OSA reduced
      this risk. It is concluded that middle-aged sleep apnoeics are at high risk of
      developing coronary artery disease if they are not treated efficiently, which
      should be considered in cardiovascular disease prevention models.

PMID- 16641121
TI  - Negligible clearance of ultrafine particles retained in healthy and affected
      human lungs.
AB  - Ambient particles are believed to be a specific health hazard, although the
      underlying mechanisms are not fully understood. There are data in the literature
      indicating fast and substantial systemic uptake of particles from the lung. The
      present authors have developed an improved method to produce ultrafine particles
      with more stable radiolabelling and defined particle size range. Fifteen subjects
      inhaled technetium 99m (99mTc)-labelled carbonaceous particles of 100 nm in size.
      Radioactivity over the lung was followed for 70 h. The clearance of these
      ultrafine particles from the lungs and specifically translocation to the
      circulation was tested. Lung retention for all subjects at 46 h was mean+/-sd
      99+/-4.6%. Cumulative leaching of 99mTc activity from the particles was 2.6+/
      0.96% at 70 h. The 24-h activity leaching in urine was 1.0+/-0.55%. No evidence
      of a quantitatively important translocation of 100-nm particles to the systemic
      circulation from the lungs was found. More research is needed to establish if the
      approximately 1% cleared activity originates from leached activity or insoluble
      translocated particles, and whether a few per cent of translocated particles is
      sufficient to cause harmful effects.

PMID- 16641122
TI  - Measurement of combined oximetry and cutaneous capnography during flexible
      bronchoscopy.
AB  - The aim of the present study was to assess the feasibility of measuring combined
      arterial oxygen saturation measured by pulse oximetry (Sp,O2) and cutaneous
      carbon dioxide tension (Pc,CO2) to monitor ventilation and quantify change in
      Pc,CO2 during bronchoscopy. Combined Sp,O2 and Pc,CO2 were measured at the ear
      lobe in 114 patients. In four patients, the ear-clip slipped and they were
      excluded. In total, 11 patients had artefacts with Sp,O2 recordings, thus, Sp,O2
      was analysed in 99 patients. Spirometry data were available in 77 patients.
      Multivariate analysis of covariance and logistic regression were used for
      statistical analyses. Mean baseline Pc,CO2 was 4.78+/-1.06 kPa (36+/-8 mmHg) and
      mean rise in the Pc,CO2 during bronchoscopy was 1.26+/-0.70 kPa (9.5+/-5.3 mmHg),
      while mean Pc,CO2 at the end of bronchoscopy was 5.85+/-1.19 kPa (44+/-9 mmHg) .
      Baseline Pc,CO2 and the lowest Sp,O2 were significantly associated with peak
      Pc,CO2 and the change in Pc,CO2 during bronchoscopy. Risk of significant
      hypoxaemia (Sp,O2<or=90%) was lower for a higher baseline Sp,O2. Peak Pc,CO2 was
      directly associated with significant hypoxaemia. There was no significant
      association in the baseline Pc,CO2, peak Pc,CO2, baseline Sp,O2 or the lowest
      Sp,O2 comparing patients with and without chronic obstructive pulmonary disease.
      In conclusion, it is feasible to measure combined pulse oximetry and cutaneous
      carbon dioxide tension effectively to monitor ventilation during flexible
      bronchoscopy.

PMID- 16641123
TI  - Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory
      response in the mouse lung.
AB  - High levels of particulate matter in ambient air are associated with increased
      respiratory and cardiovascular health problems. It has been hypothesised that it
      is the ultrafine particle fraction (diameter <100 nm) that is largely responsible
      for these effects. To evaluate the associated mechanisms on a molecular level,
      the current authors applied an expression profiling approach. Healthy mice were
      exposed to either ultrafine carbon particles (UFCPs; mass concentration 380
      microg x m(-3)) or filtered air for 4 and 24 h. Histology of the lungs did not
      indicate any pathomorphological changes after inhalation. Examination of the
      bronchoalveolar lavage fluid revealed a small increase in polymorphonuclear cell
      number (ranging 0.6-1%) after UFCP inhalation, compared with clean air controls,
      suggesting a minor inflammatory response. However, DNA microarray profile
      analysis revealed a clearly biphasic response to particle exposure. After 4 h of
      inhalation, mainly heat shock proteins were induced, whereas after 24 h,
      different immunomodulatory proteins (osteopontin, galectin-3 and lipocalin-2)
      were upregulated in alveolar macrophages and septal cells. In conclusion, these
      data indicate that inhalation of ultrafine carbon particles triggers a biphasic
      pro-inflammatory process in the lung, involving the activation of macrophages and
      the upregulation of immunomodulatory proteins.

PMID- 16641124
TI  - Safety and feasibility of exhaled breath condensate collection in ventilated
      infants and children.
AB  - The aim of this study was to develop a technique for the collection of exhaled
      breath condensate (EBC) from ventilated children and assess its safety and
      feasibility. Collection of EBC is used to investigate markers of oxidative stress
      in the lower airway. No studies have assessed its safety in ventilated children.
      An in vitro model was developed by connecting a ventilator to an artificial lung;
      14 clinical and ventilatory parameters were measured during EBC collection from
      ventilated children. Levels of 8-isoprostane were measured following collection
      with and without humidification of the inhaled gas. Amount of water vapour
      collected was linearly related to time and to minute ventilation in the in vitro
      model. EBC collections (n = 68) were made from ventilated children. In the
      nonhumidified group, the mean (range) positive end-expiratory pressure increased
      by 4.1% (2.8-5.5%) and the peak inspiratory flow decreased by 6.1% (11.0-1.3%)
      during collection. Detectable levels of 8-isoprostane were only found in 10 out
      of 18 nonhumidified EBC samples (median (range) 4.7 pg x mL(-1) (0-5.8)).
      Collection of exhaled breath condensate from ventilated infants and children is
      feasible and safe. Discontinuation of humidification is likely to be important in
      standardising the measurement of inflammatory parameters in exhaled breath
      condensate collected from ventilated children.

PMID- 16641125
TI  - Ultrastructure of the reticular basement membrane in asthmatic adults, children
      and infants.
AB  - Reticular basement membrane (RBM) thickening in asthma is considered to be the
      result of subepithelial fibrosis. Thus, the RBM in asthma should contain an
      excess of fibrils identified as interstitial collagen and the ratio of fibril to
      matrix should be increased above normal levels. Electron micrographs of the RBM
      were compared with those of interstitial collagen deeper in the bronchial wall
      using endobronchial biopsy specimens from adult asthmatics (aged 18-41 yrs (n =
      10)), children with difficult asthma (aged 6-16 yrs (n = 10)), wheezy infants
      with reversible airflow limitation (aged 0.3-2 yrs (n = 10)) and age-matched
      nonasthmatic controls: 10 adults, nine children and nine symptomatic infants with
      normal lung function. Fibrils in the RBM were significantly thinner (median
      (range) width 39 (30-52) nm versus 59 (48-73) nm), and fewer fibrils were banded
      than in the interstitial collagen (ratio of banded to non-banded fibrils 0.08 (0
      0.17) versus 0.22 (0-1.3)). The ratio of fibrils to matrix in the thickened RBM
      of asthmatics did not differ from that of their respective controls (1.34 (0.63
      2.49) versus 1.18 (0.31-2.6)). The ratio of fibril to matrix in the thickened
      reticular basement membrane of asthmatics is normal, and, contrary to what is
      expected in fibrosis, the fibrils do not resemble those of interstitial collagen.

PMID- 16641126
TI  - Lack of tolerance to the protective effect of montelukast in exercise-induced
      bronchoconstriction in children.
AB  - The effect over time of regular treatment with montelukast (MNT) in inhibiting
      exercise-induced bronchoconstriction (EIB) has never been evaluated in children.
      The aim of the present study was to examine the preventive effect of MNT against
      EIB in children at different time-points over a 4-week treatment period. Thirty
      two asthmatic children (aged 6-12 yrs) were enrolled in a double-blinded,
      randomised, parallel group design to receive a 4-week treatment with MNT (5 mg
      chewable tablets administered once daily in the evening) or placebo. Exercise
      challenge was performed at baseline and after 3, 7 and 28 days of treatment, 20
      24 h after dosing. MNT was significantly more protective than placebo against EIB
      at each time. The mean percentage drop of forced expiratory volume in one second
      (FEV1) was 24.6, 13.6, 12.0 and 11.6 for MNT, and 24.4, 22.4, 21.8 and 21.0 for
      placebo, at baseline and after 3, 7 and 28 days, respectively. For each drug, no
      significant difference in the percentage drop of FEV1 was found between different
      days. Regular treatment with montelukast provided significant protection against
      exercise-induced bronchoconstriction in asthmatic children over a 4-week period
      with no tolerance to the bronchoprotective effect.

PMID- 16641127
TI  - Relations among questionnaire and laboratory measures of rhinovirus infection.
AB  - Due to high incidence and quality-of-life impact, upper respiratory infection
      substantially impacts on population health. To test or compare treatment
      effectiveness, a well-designed and validated illness-specific quality-of-life
      instrument is needed. Data reported in the current study were obtained from a
      trial testing echinacea for induced rhinovirus infection. Laboratory-assessed
      biomarkers included interleukin (IL)-8, nasal neutrophil count (polymorphonuclear
      neutrophils (PMN)), mucus weight, viral titre and seroconversion. The
      questionnaires used included the general health short form (SF)-8 (24-h recall
      version), the eight-item Jackson cold scale, and the 44-item Wisconsin Upper
      Respiratory Symptom Survey (WURSS). In total, 399 participants were inoculated
      with rhinovirus and monitored over 2,088 person-days. Statistically significant
      associations were found among nearly all variables. Between-questionnaire
      correlations were: WURSS-Jackson = 0.81; WURSS-SF-8 = 0.62; and Jackson-SF-8 =
      0.60. Correlations with laboratory values were as follows: WURSS-mucus weight =
      0.53; Jackson-mucus weight = 0.55; WURSS-viral titre = 0.37; Jackson-viral titre
      = 0.46; WURSS-IL-8 = 0.31; Jackson-IL-8 = 0.36; WURSS-PMN = 0.31; and Jackson-PMN
      = 0.28. Neither WURSS nor Jackson yielded satisfactory cut-off scores for
      diagnosis of infection. Symptomatic and biological outcomes of upper respiratory
      infection are highly variable, with only modest associations. While Wisconsin
      Upper Respiratory Symptom Survey and Jackson questionnaires both correlate with
      biomarkers, neither is a good predictor of induced infection. The inclusion of
      functional and quality-of-life items in the Wisconsin Upper Respiratory Symptom
      Survey does not significantly decrease the strength of association with
      laboratory-assessed biomarkers.

PMID- 16641128
TI  - Commentary: fuelling the fire--systemic inflammation and development of lung
      disease in the general community.

PMID- 16641129
TI  - Patient satisfaction with large-scale out-of-hours primary health care in The
      Netherlands: development of a postal questionnaire.
AB  - BACKGROUND: Since the turn of the millennium, out-of-hours primary health care in
      The Netherlands has faced a substantial change from small locum groups towards
      large GP cooperatives. Improving the quality of care requires evaluation of
      patient satisfaction. OBJECTIVE: To develop a reliable postal questionnaire for
      wide-scale use by patients contacting their out-of-hours GP cooperative and to
      present the results of a national survey. METHODS: Literature review and
      interviews with both patients and health carers were carried out to identify
      issues of potential relevance, followed by two postal pilot studies and
      additional interviews to remove or rephrase items. Finally, postal questionnaires
      were sent to 14,400 people who contacted one of 24 GP cooperatives in The
      Netherlands. RESULTS: Overall response was 52.2% for all types of contact. Three
      scales were identified prior to the field phase and confirmed by principal
      components analysis: telephone nurse, doctor and organization. Reliability was
      high, with Cronbach's alphas and intraclass correlation coefficients exceeding
      0.70 for all scales. Only items in the organization scale showed clear
      differences among the participating cooperatives. Respondents receiving telephone
      advice showed lower levels of satisfaction than respondents with other types of
      contact (P < 0.001); centre consultation scored lower than home visit (P < 0.030
      or less for all differences). CONCLUSION: A reliable measure of patient
      satisfaction has been developed that can also be used for the comparison of GP
      cooperatives on an organizational level. Overall satisfaction was high, showing
      highest levels for home visit and lowest levels for telephone advice.

PMID- 16641130
TI  - Global analysis of the human gastric epithelial transcriptome altered by
      Helicobacter pylori eradication in vivo.
AB  - OBJECTIVE: The transcriptional profile of gastric epithelial cell lines
      cocultured with Helicobacter pylori and the global gene expression of whole
      gastric mucosa has been described previously. We aimed to overcome limitations of
      previous studies by determining the effects of H pylori eradication on the
      transcriptome of purified human gastric epithelium using each patient as their
      own control. DESIGN: Laser capture microdissection (LCM) was used to extract mRNA
      from paraffin-embedded antral epithelium from 10 patients with peptic ulcer
      disease, before and after H pylori eradication. mRNA was reverse transcribed and
      applied on to Affymetrix cDNA microarray chips customised for formalin-fixed
      tissue. Differentially expressed genes were identified and a subset validated by
      real-time polymerase chain reaction (PCR). RESULTS: A total of 13 817 transcripts
      decreased and 9680 increased after H pylori eradication. Applying cut-off
      criteria (p<0.02, fold-change threshold 2.5) reduced the sample to 98
      differentially expressed genes. Genes detected included those previously
      implicated in H pylori pathophysiology such as interleukin 8, chemokine ligand 3,
      beta defensin and somatostatin, as well as novel genes such as GDDR (TFIZ1),
      chemokine receptors 7 and 8, and gastrokine. CONCLUSIONS: LCM of archival
      specimens has enabled the identification of gastric epithelial genes whose
      expression is considerably altered after H pylori eradication. This study has
      confirmed the presence of genes previously implicated in the pathogenesis of H
      pylori, as well as highlighted novel candidates for further investigation.

PMID- 16641131
TI  - Modulation of iron transport proteins in human colorectal carcinogenesis.
AB  - BACKGROUND AND AIMS: Total body iron and high dietary iron intake are risk
      factors for colorectal cancer. To date there is no comprehensive characterisation
      of iron transport proteins in progression to colorectal carcinoma. In this study,
      we examined expression of iron import (duodenal cytochrome b (DCYTB), divalent
      metal transporter 1 (DMT1), and transferrin receptor 1 (TfR1)) and export
      (hephaestin (HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma.
      METHODS: Perl's staining was used to examine colonocyte iron content. Real time
      polymerase chain reaction (PCR) and western blotting were used to examine mRNA
      and protein levels of the molecules of interest in 11 human colorectal cancers.
      Semiquantitative immunohistochemistry was used to verify protein levels and
      information on cellular localisation. The effect of iron loading on E-cadherin
      expression in SW480 and Caco-2 cell lines was examined by promoter assays, real
      time PCR and western blotting. RESULTS: Perl's staining showed increased iron in
      colorectal cancers, and there was a corresponding overexpression of components of
      the intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron
      exporter FPN was also overexpressed, but its intracellular location, combined
      with reduced HEPH levels, suggests reduced iron efflux in the majority of
      colorectal cancers examined. Loss of HEPH and FPN expression was associated with
      more advanced disease. Iron loading Caco-2 and SW480 cells caused cellular
      proliferation and E-cadherin repression. CONCLUSIONS: Progression to colorectal
      cancer is associated with increased expression in iron import proteins and a
      block in iron export due to decreased expression and aberrant localisation of
      HEPH and FPN, respectively. This results in increased intracellular iron which
      may induce proliferation and repress cell adhesion.

PMID- 16641132
TI  - Factors related to misperception of physical activity in The Netherlands and
      implications for health promotion programmes.
AB  - With respect to health risk behaviours, many people are unaware of their own risk
      behaviour and regard their behaviour as more healthy than it really is. This
      article studied differences between people with and without misperception of
      their physical activity with respect to several reference points: the social
      comparison style of people (upward, equal and downward); the body self-image with
      regard to their weight [body mass index (BMI) and self-rated weight]; and
      linkages of physical activity with different outcome expectancies (health,
      appearance, weight, feeling fit, relaxation and stress relief). Results from 516
      respondents (response 52%; 56% women) with a mean age of 53.7 years found that
      respondents who incorrectly think that their physical activity is adequate
      (overestimators) tend to rate their physical activity more often in comparison to
      others. Furthermore, overestimators and people who correctly think they exercise
      enough more often use downward comparison, while underestimators and people who
      know they exercise too little mostly use upward comparison. People who, rightly
      or not, think their weight is adequate or who have a lower BMI, more often assume
      that their physical activity is sufficient or high. People who, rightly or not,
      think that their physical activity is adequate more often score higher on other
      reasons to be physically active besides health. Increasing the accuracy of
      people's self-perceptions of physical activity may be important to incorporate
      into strategies to promote physical activity in populations at risk of
      inactivity.

PMID- 16641133
TI  - Critical involvement of IL-12 in IFN-gamma induction by calcineurin antagonists
      in activated human lymphocytes.
AB  - Calcineurin antagonists are known as potent immunosuppressants working
      particularly on T cells by virtue of their capacity to block nuclear factor of
      activated T cell (NFAT) activation and translocation to the nucleus. In addition
      to interleukin (IL)-2 suppression, T helper cell type 1 (Th1) as well as Th2
      cytokine transcription is blocked by calcineurin antagonists. Here, we show that
      calcineurin antagonists such as cyclosporin A (CsA) or tacrolimus can markedly
      enhance the production of interferon-gamma (IFN-gamma) by human T cells. This
      increased IFN-gamma production is dependent on T cell receptor (TCR) and CD28
      signaling as well as on the presence of IL-12. IL-27, which could mimic the
      effect of IL-12, was however less potent in inducing IFN-gamma production in the
      presence of CsA and TCR stimulation. Other cytokines such as IL-23, IL-18, IL-2,
      or the Th2-related cytokine IL-4 are not able to support a calcineurin antagonist
      dependent up-regulation of IFN-gamma. CsA-dependent IFN-gamma production is
      observable in therapeutic concentrations. The effect is independent of IL-10 or
      IL-4, as addition of these cytokines could not inhibit the CsA-induced IFN-gamma
      production. The effect of calcineurin antagonists is associated with an increased
      c-fos expression and DNA-binding activity of the transcription factor activated
      protein-1 but not with increased DNA-binding activity of T-bet. Our study further
      supports the relevance of known calcineurin activities other than NFAT
      activation. The presented data may help to explain why concomitant infections
      (resulting in increased IL-12 expression) under therapy with calcineurin
      antagonists often have a negative impact on the activity of the underlying
      disease (e.g., autoimmune disease).

PMID- 16641134
TI  - Assembly of the phagocyte NADPH oxidase complex: chimeric constructs derived from
      the cytosolic components as tools for exploring structure-function relationships.
AB  - Phagocytes generate superoxide (O2*-) by an enzyme complex known as reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Its catalytic
      component, responsible for the NADPH-driven reduction of oxygen to O2*-, is
      flavocytochrome b559, located in the membrane and consisting of gp91phox and
      p22phox subunits. NADPH oxidase activation is initiated by the translocation to
      the membrane of the cytosolic components p47phox, p67phox, and the GTPase Rac.
      Cytochrome b559 is converted to an active form by the interaction of gp91phox
      with p67phox, leading to a conformational change in gp91phox and the induction of
      electron flow. We designed a new family of NADPH oxidase activators, represented
      by chimeras comprising various segments of p67phox and Rac1. The prototype
      chimera p67phox (1-212)-Rac1 (1-192) is a potent activator in a cell-free system,
      also containing membrane p47phox and an anionic amphiphile. Chimeras behave like
      bona fide GTPases and can be prenylated, and prenylated (p67phox -Rac1) chimeras
      activate the oxidase in the absence of p47phox and amphiphile. Experiments
      involving truncations, mutagenesis, and supplementation with Rac1 demonstrated
      that the presence of intrachimeric bonds between the p67phox and Rac1 moieties is
      an absolute requirement for the ability to activate the oxidase. The presence or
      absence of intrachimeric bonds has a major impact on the conformation of the
      chimeras, as demonstrated by fluorescence resonance energy transfer, small angle
      X-ray scattering, and gel filtration. Based on this, a "propagated wave" model of
      NADPH oxidase activation is proposed in which a conformational change initiated
      in Rac is propagated to p67phox and from p67phox to gp91phox.

PMID- 16641135
TI  - Recognition ligands on apoptotic cells: a perspective.
AB  - The process of apoptosis includes critically important changes on the cell
      surface that lead to its recognition and removal. The recognition also generates
      a number of other local tissue responses including suppression of inflammation
      and immunity. It is surprising that the ligands generated on the apoptotic cell,
      which mediates these effects, have received relatively little attention. Some of
      these candidate molecules and possible mechanisms for their surface expression
      are addressed herein, with particular emphasis on phosphatidylserine and
      calreticulin. However, exposure of such ligands is exclusive to apoptosis and
      may, in fact, occur on viable cells. To partially explain the lack of response to
      such potential stimuli, the presence on viable cells of "don't eat me" signals,
      in this case, CD47 is suggested to prevent such unwarranted actions. Loss or
      inactivation of the don't eat me CD47 effects accompanies apoptosis and now allow
      the cells to be recognized and cleared.

PMID- 16641136
TI  - Dendritic cells in pathogen recognition and induction of immune responses: a
      functional genomics approach.
AB  - At the 38th Annual Meeting of the Society for Leukocyte Biology held in Oxford
      this year, the biology of dendritic cells (DCs) and macrophages was discussed. In
      particular, functional genomics approaches were presented to investigate
      transcriptional changes during microbe and phagocytes interactions. Here, we
      report functional genomics studies likely to be of interest to the Journal of
      Leukocyte Biology readers with a particular emphasis on DC biology. DCs are
      professional antigen-presenting cells, which are essential for the initiation and
      regulation of natural killer, T, and T regulatory cell responses. Immature DCs,
      resident in peripheral sites, are specialized in antigen capture and continually
      sample soluble and particulate antigens in their local environment. DCs express
      receptors for cytokines, chemokines, endogenous danger signals, and microbial
      structures. The interactions between DCs and microorganism are complex, but
      progress in the past few years has shed light on several aspects of these
      processes. Infectious disease is the result of an intimate relationship between
      pathogens and hosts. Thus, understanding the cross-talk between host and pathogen
      is essential to improve our knowledge of infectious disease. Functional genomics
      and proteomics applied to DCs and macrophage biology are now providing powerful
      tools to dissect, at the molecular level, host-pathogen interactions.

PMID- 16641137
TI  - Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in
      Crohn's disease.
AB  - Apoptosis of active T lymphocytes constitutes a major control mechanism of immune
      homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T
      lymphocytes against enteric bacteria is the key event triggering intestinal
      inflammation. Resistance of lymphocytes to apoptosis has been proposed as the
      pathogenetic defect. We examined the influence of bacteria-mucosa interactions on
      apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from
      12 patients with Crohn's disease. Mucosal explants from each specimen were
      cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN
      114 001, or no bacteria. Cytokine release was measured in supernatant, and
      mononuclear cells were isolated for phenotypic characterization and Bcl-2 family
      protein expression. Coculture of inflamed tissue with L. casei significantly
      reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P <
      0.05). In addition, coculture with L. casei significantly reduced the number of T
      cells displaying the IL-2 receptor in the lamina propria. Expression of the
      antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after
      coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end
      labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no
      significant effect. In conclusion, L. casei reduces the number of activated T
      lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local
      microecology may restore immune homeostasis.

PMID- 16641138
TI  - Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression,
      leukocyte recruitment, and hepatocellular apoptosis in septic liver injury.
AB  - Rho-kinase signaling regulates important features of inflammatory reactions.
      Herein, we investigated the effect and mechanisms of action of the Rho-kinase
      inhibitor fasudil in endotoxemic liver injury. C57/BL/6 mice were challenged with
      lipopolysaccharide (LPS) and D-galactosamine, with or without pretreatment with
      the Rho-kinase inhibitor fasudil. Six hours after endotoxin challenge, leukocyte
      endothelium interactions in the hepatic microvasculature were studied by use of
      intravital fluorescence microscopy and tumor necrosis factor alpha (TNF-alpha);
      CXC chemokines as well as liver enzymes and apoptosis were determined.
      Administration of fasudil reduced LPS-induced leukocyte adhesion in
      postsinusoidal venules and sequestration in sinusoids. Moreover, we found that
      fasudil abolished extravascular infiltration of leukocytes as well as production
      of TNF-alpha and CXC chemokines in the liver of endotoxemic mice. Liver enzymes
      and hepatocellular apoptosis were markedly reduced, and sinusoidal perfusion was
      improved significantly in endotoxemic mice pretreated with fasudil. Our novel
      data document that fasudil is a potent inhibitor of endotoxin-induced expression
      of TNF-alpha and CXC chemokines as well as leukocyte infiltration and
      hepatocellular apoptosis in the liver. Based on the present findings, it is
      suggested that inhibition of the Rho-kinase signaling pathway may be a useful
      target in the treatment of septic liver injury.

PMID- 16641139
TI  - Ischemia-induced angiogenesis: role of inflammatory response mediated by P
      selectin.
AB  - P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and
      platelets. P-selectin mediates the tethering and rolling of leukocytes along the
      endothelium, an early step of leukocyte extravasation. Although inflammation is a
      requisite process for ischemia-induced angiogenesis, little is known regarding
      the role of P-selectin in angiogenesis in the setting of tissue ischemia. We
      examined whether ischemia-induced angiogenesis is altered in P-selectin knockout
      (P-selectin(-/-)) mice. Angiogenesis was evaluated in a surgically induced hind
      limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological
      capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb
      LDBF ratio was persistently lower in P-selectin(-/-) mice compared with wild-type
      (WT) mice. CD was also significantly lower in P-selectin(-/-) mice than in WT
      mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory
      leukocytes infiltrated into the ischemic tissues in P-selectin(-/-) mice than in
      WT mice, and immunohistochemical analysis revealed the number of infiltrated
      leukocytes expressing vascular endothelial growth factor was also decreased in P
      selectin(-/-) mice. P-selectin mRNA expression was augmented after hind-limb
      ischemia in WT mice. In conclusion, P-selectin may play an important role in
      ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell
      infiltration. P-selectin would become one possible target molecule for modulating
      inflammatory angiogenesis.

PMID- 16641140
TI  - p120 nucleolar-proliferating antigen is a direct target of G-CSF signaling during
      myeloid differentiation.
AB  - Granulocyte-colony stimulating factor (G-CSF) is an essential cytokine, which
      contributes to proliferation and differentiation of granulocyte precursor cells
      in the bone marrow. Despite recent progress in understanding G-CSF signaling
      events, the mechanisms that underlie the distinct spectrum of biological
      functions attributed to G-CSF-mediated gene expression remain unclear. Previous
      studies have identified a number of genes, which are up-regulated in G-CSF
      stimulated myeloid precursor cells. In this study, we sought to identify
      additional target genes of G-CSF-mediated proliferation and/or differentiation.
      cDNA representational difference analysis was used with the 32Dcl3 cell line as a
      model system to isolate genes, which are up-regulated in an immediate-early
      manner upon G-CSF stimualtion. We isolated p120 nucleolar-proliferation antigen
      (NOL1), a highly conserved, nucleolar-specific, RNA-binding protein of unknown
      function, and confirmed its expression by Northern blot analysis in 4-h, G-CSF
      induced 32Dcl3 cells. Isolation of a mouse p120 genomic clone revealed the
      presence of a signal tranducer and activator of transcription (STAT)-binding site
      in the first intron of the gene. We demonstrate the importance of STAT3 and STAT5
      in mediating the G-CSF response with respect to p120 expression by transient
      transfection analysis, oligonucleotide pull-down assays, and the loss of p120
      expression in the bone marrow of mice lacking normal STAT3 signaling. In
      addition, overexpression of p120 in G-CSF-induced 32D cells revealed normal,
      morphologic maturation and growth characteristics but loss of lactoferrin
      expression, a marker of normal neutrophil maturation, suggesting that
      inappropriate expression of the p120 gene can result in aberrant neutrophil
      maturation.

PMID- 16641141
TI  - Falls definition--reliability of patients' own reports.

PMID- 16641142
TI  - Nurse-led implementation of the single assessment process in primary care: a
      descriptive feasibility study.
AB  - OBJECTIVE: to determine the resources required to carry out the single assessment
      process in primary care. DESIGN: prospective descriptive study. SETTING: one
      urban primary care practice, Southampton. PARTICIPANTS: nine hundred and forty
      four people aged 70+ years, registered with the practice, not living in a
      residential/nursing home, or terminally ill. INTERVENTION: participants were sent
      the six-item Sherbrooke questionnaire (case-finding tool). Non-responders were re
      mailed after 4 weeks. All those scoring 4, 5 or 6 and a randomly selected half of
      those scoring 2 or 3 were offered overview assessment and comprehensive
      assessment as indicated by the Minimum Data Set for Home Care protocol. The nurse
      assessor identified unmet needs and agreed an action plan with participants.
      Another researcher conducted semi-structured interviews with a purposive sample
      of 26 participants to elicit their views of the process. MAIN OUTCOME MEASURES:
      response rates/scores of Sherbrooke questionnaire; numbers/characteristics of
      people requiring overview and comprehensive assessments; nature of resulting
      recommendations/referrals and impact on other agencies; resources required; views
      of service users. RESULTS: eight hundred and sixty-three (91%) participants
      replied. Five hundred and seven (54%) scored 2+, triggering an overview
      assessment, which was offered to 307. One hundred and twenty-four participants
      (40%) accepted; 64 (52%) had unmet needs (median 8 each, range 2-18), resulting
      in 34 referrals within the practice including four case conferences, and 21 to
      community/secondary health services. Few participants with a Sherbrooke score of
      2 required comprehensive assessment. Users perceived the process as acceptable
      and useful, but not always relevant to their current needs. CONCLUSION: targeting
      those scoring 3+ on the Sherbrooke questionnaire (28% of sample) may improve the
      identification of patients who would benefit from further assessment. A contact
      approach rather than a case-finding one may improve the relevance of this process
      to older people.

PMID- 16641143
TI  - Vitamin D supplementation and the prevention of fractures and falls: results of a
      randomised trial in elderly people in residential accommodation.
AB  - OBJECTIVES: To determine whether vitamin D supplementation reduces the risk of
      fracture or falls in elderly people in care home accommodation. DESIGN: A
      randomised controlled trial of cluster design. SETTING AND SUBJECTS: 223
      Residential units (mainly identical 30-bedded units), within 118 homes for
      elderly people throughout Britain, with 3,717 participating residents (76% women,
      average age 85 years). The units provided mainly or entirely residential care
      (35% of residents), nursing care (42%) or care for elderly mentally infirm (EMI)
      residents (23%). METHODS: Participants were randomly allocated by residential
      unit (cluster design) to a treated group offered ergocalciferol 2.5 mg every 3
      months (equivalent to a daily dose of 1,100 IU), or to a control group. Fractures
      were reported by staff and confirmed in hospital, and routinely collected data on
      reported falls were obtained. RESULTS: After median follow-up of 10 months
      (interquartile range 7-14 months), 64 (3.6%) of 1,762 vitamin D-treated residents
      and 51 (2.6%) of 1,955 controls had one or more non-vertebral fractures, and 24
      (1.3%) and 20 (1.0%), respectively, had a hip fracture. The proportion reporting
      at least one fall was 44% in vitamin D-treated and 43% in control residents. The
      differences between the vitamin D and control groups were not statistically
      significant. The incidence of all non-vertebral fractures in the care homes (3.2%
      per year) and of hip fractures (1.1% per year) was low, similar to rates in
      elderly people in sheltered accommodation, and the pre-treatment serum 25-hydroxy
      vitamin D concentration was high [median 47 nmol/l, measured in a 1% (n = 18)
      sample]. CONCLUSIONS: We found no evidence that vitamin D prevents fractures or
      falls in elderly people in care home accommodation.

PMID- 16641144
TI  - Essential tremor-the most common movement disorder in older people.
AB  - Essential tremor (ET) affects approximately 4% of the population above 65 years
      of age. The traditional view that ET is a familial monosymptomatic disorder with
      a benign prognosis has recently been challenged, as it is now known to be a
      progressive and clinically heterogeneous condition with sporadic and familial
      forms. The pathogenesis of ET is not fully understood, though a disordered
      central mechanism is the most likely site of origin with possible modulation by
      muscle adrenoreceptors. The limited post-mortem studies have not shown consistent
      abnormalities in the brains of ET patients. ET is often misdiagnosed as
      Parkinson's disease, particularly in the older population. Tremor amplitude
      increases with age, accounting for substantial disability in older people.
      Current therapy (drugs and neurosurgery) has significant limitations in older
      people. A better understanding of its pathophysiology in the future will help in
      developing more effective therapy, including neuroprotective strategies.

PMID- 16641145
TI  - PSPC1, NONO, and SFPQ are expressed in mouse Sertoli cells and may function as
      coregulators of androgen receptor-mediated transcription.
AB  - In Sertoli cells of testis, androgen receptor-regulated gene transcription plays
      an indispensable role in maintaining spermatogenesis. Androgen receptor activity
      is modulated by a number of coregulators which are associated with the androgen
      receptor. Non-POU-domain-containing, octamer binding protein (NONO), a member of
      the DBHS-containing proteins, complexes with androgen receptor and functions as a
      coactivator for the receptor. Paraspeckle protein 1 alpha isoform (PSPC1,
      previously known as PSP1) and Splicing factor, proline- and glutamine-rich (SFPQ,
      previously known as PSF), other members of the DBHS-containing proteins, are also
      found in androgen receptor complexes, suggesting that these DBHS-containing
      proteins may cooperatively regulate androgen receptor-mediated gene
      transcription. We demonstrated that PSPC1, NONO, and SFPQ are coexpressed in
      Sertoli cell line TTE3 and interact reciprocally. The effect of the DBHS
      containing proteins on the transcriptional activity was assessed using the
      construct containing androgen-responsive elements followed by a luciferase gene.
      The results showed that all the DBHS-containing proteins activate androgen
      receptor-mediated transcription, and PSPC1 is the most effective coactivator
      among them. Furthermore, we confirmed the presence of PSPC1, NONO, and SFPQ
      proteins in Sertoli cells of adult mouse testis sections. These observations
      suggest that PSPC1, NONO, and SFPQ form complexes with each other in Sertoli
      cells and may regulate androgen receptor-mediated transcriptional activity.

PMID- 16641146
TI  - Differential endocrine regulation of genes enriched in initial segment and distal
      caput of the mouse epididymis as revealed by genome-wide expression profiling.
AB  - We have performed genome-wide expression profiling of endocrine regulation of
      genes expressed in the mouse initial segment (IS) and distal caput of the
      epididymis by using Affymetrix microarrays. The data revealed that of the 15 020
      genes expressed in the epididymis, 35% were enriched in one of the two regions
      studied, indicating that differential functions can be attributed to the IS and
      the more distal caput regions. The data, furthermore, showed that 27% of the
      genes expressed in the IS and/or distal caput epididymidis are under the
      regulation of testicular factors present in the duct fluid, while bloodborne
      androgens can regulate for 14% of them. This is in line with the high testis
      dependency of epididymal physiology. We then focused on genes with moderate or
      strong expression, showing strict segment enrichment and strong dependency on
      testicular factors. Analyses of the 59 genes, including upregulated and
      downregulated genes, fulfilling the criteria indicated that the expression of 18
      (17 downregulated genes; 1 upregulated gene) of 19 gonadectomy-responsive genes
      enriched in the IS was not maintained by the androgen treatment, whereas the
      expression of all six downregulated genes enriched in the distal caput and the
      majority of those with no strict segment enrichment of expression (28 of 34;
      consisting of 23 downregulated and 5 upregulated genes) were maintained by
      androgens. Hence, it is evident that testicular factors other than androgens are
      important for the expression of IS-enriched genes, whereas the expression of
      distal caput-enriched genes is typically regulated by androgens. Identical data
      were obtained by independent clustering analyses performed for the expression
      data of 3626 epididymal genes. Several novel genes with putative involvement in
      epididymal sperm maturation, such as a disintegrin and metallopeptidase domain 28
      (Adam28) and a solute carrier organic anion transporter family, member 4C1
      (Slco4c1), were identified, indicating that this approach is successful for
      identifying novel epididymal genes.

PMID- 16641147
TI  - Distinct regulation by steroids of messenger RNAs for FSHR and CYP19A1 in bovine
      granulosa cells.
AB  - Steroidal regulation of gene expression in follicular cells is not completely
      defined. Granulosa cells from 5 mm bovine follicles were cultured and treated and
      steady-state mRNA levels determined for FSHR (follicle-stimulating hormone
      receptor) and CYP19A1 (aromatase). Cells were treated for 5 days with (0.1-300
      ng/ml) 17beta-estradiol (E2), testosterone (T), or 5alpha-dihydrotestosterone
      (DHT). FSHR mRNA was increased by T and DHT but not E2. In contrast, CYP19A1 mRNA
      was induced by all doses of E2 but only high doses of T and DHT. Similarly,
      varying treatment duration (1-5 days) showed that FSHR was increased by T and DHT
      and CYP19A1 mRNA increased by E2 and T at all times. Synergism between steroid
      hormones and FSH or forskolin was also evaluated. FSH or E2 did not alter FSHR
      mRNA and did not enhance DHT stimulation of FSHR mRNA. In contrast, DHT alone had
      no effect on CYP19A1 mRNA but synergized with FSH plus E2 to increase CYP19A1
      mRNA, probably due to induction of FSHR by DHT. Effects of E2 and T on CYP19A1
      were blocked by ICI 182,780, indicating mediation by estrogen receptors. However,
      the specific androgen receptor antagonist bicalutamide did not block E2 or T
      effects on CYP19A1 but did block T and DHT stimulation of FSHR. Thus, FSHR is
      specifically regulated through androgen receptor, whereas CYP19A1 is regulated by
      multiple pathways, including estrogen receptors and cAMP/protein kinase A induced
      by FSHR activation in granulosa cells. These inter- and intracellular regulatory
      mechanisms may be critical for normal follicle growth and dominant follicle
      selection.

PMID- 16641148
TI  - Adeno-associated virus-mediated CTLA4Ig gene transfer protects MHC-mismatched
      renal allografts from chronic rejection.
AB  - Short-term results of renal transplantation have improved considerably in the
      past 20 yr; however, similar improvements in long-term outcome have not been
      achieved. The primary cause of late graft loss is chronic rejection that might be
      treated by gene therapeutic approaches. Ideally, one would like to impair locally
      the contact between transplant antigen and the host immune system without
      compromising the generalized immune competence of the recipient. This can be
      achieved by local expression of the therapeutic protein in the site of interest
      using gene therapy. Here it is shown that chronic allograft rejection can be
      prevented effectively by local delivery of recombinant adeno-associated virus
      (AAV) vectors that encode the CTLA4Ig immunosuppressant protein to the donor
      kidney in a fully MHC-mismatched rat strain combination. AAV CTLA4Ig prevented
      progressive proteinuria and protected transplant kidneys from renal structural
      injury. A population of anergic T cells with regulatory activity, which
      eventually were responsible for the induction of tolerance, were found in
      recipient lymph nodes and in the graft as long as 120 d after transplantation.
      These data indicate that AAV-mediated CTLA4Ig gene transfer to donor graft
      represents a promising tool to prevent the onset of chronic rejection and
      circumvent the unwanted systemic adverse effects of the administration of
      immunomodulatory protein.

PMID- 16641149
TI  - Validity of International Classification of Diseases, Ninth Revision, Clinical
      Modification Codes for Acute Renal Failure.
AB  - Administrative and claims databases may be useful for the study of acute renal
      failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the
      corresponding diagnosis and procedure codes is unknown. The performance
      characteristics of International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum
      creatinine-based definitions of ARF in 97,705 adult discharges from three Boston
      hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical
      records in 150 patients with ARF-D and 150 control patients. As compared with a
      diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF
      had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of
      47.9%, and negative predictive value of 96.1%. As compared with review of medical
      records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and
      negative predictive value of 90.0%. It is concluded that administrative databases
      may be a powerful tool for the study of ARF, although the low sensitivity of ARF
      codes is an important caveat. The excellent performance characteristics of ICD-9
      CM codes for ARF-D suggest that administrative data sets may be particularly well
      suited for research endeavors that involve patients with ARF-D.

PMID- 16641150
TI  - Tonicity-responsive enhancer binding protein is an essential regulator of
      aquaporin-2 expression in renal collecting duct principal cells.
AB  - Tonicity-responsive enhancer binding protein (TonEBP) plays a key role in
      protecting renal cells from hypertonic stress by stimulating transcription of
      specific genes. Under hypertonic conditions, TonEBP activity is enhanced via
      increased nuclear translocation, transactivation, and abundance. It was reported
      previously that hypertonicity exerted a dual, time-dependent effect on
      vasopressin-inducible aquaporin-2 (AQP2) expression in immortalized mouse
      collecting duct principal cells (mpkCCDcl4). Whereas AQP2 abundance decreased
      after 3 h of hyperosmotic challenge, it increased after 24 h of hypertonic
      challenge. This study investigated the role that TonEBP may play in these events
      by subjecting mpkCCDcl4 cells to 3 or 24 h of hypertonic challenge. Hypertonic
      challenge increased TonEBP mRNA and protein content and enhanced TonEBP activity
      as illustrated by both increased TonEBP-dependent luciferase activity and mRNA
      expression of several genes that are targeted by TonEBP. Irrespective of the
      absence or presence of vasopressin, decreased TonEBP activity in cells that were
      transfected with either TonEBP small interfering RNA or an inhibitory form of
      TonEBP strongly reduced AQP2 mRNA and protein content under iso-osmotic
      conditions and blunted the increase of AQP2 abundance that was induced after 24 h
      of hypertonic challenge. Conversely, decreased TonEBP activity did not
      significantly alter reduced expression of AQP2 mRNA that was induced by 3 h of
      hypertonic challenge. Mutation of a TonE enhancer element located 489 bp upstream
      of the AQP2 transcriptional start site abolished the hypertonicity-induced
      increase of luciferase activity in cells that expressed AQP2 promoter-luciferase
      plasmid constructs, indicating that TonEBP influences AQP2 transcriptional
      activity at least partially by acting directly on the AQP2 promoter. These
      findings demonstrate that in collecting duct principal cells, TonEBP plays a
      central role in regulating AQP2 expression by enhancing AQP2 gene transcription.

PMID- 16641151
TI  - Racial differences in the prevalence of chronic kidney disease among participants
      in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
      Study.
AB  - The racial disparity in the incidence of ESRD exemplified by the three- to four
      fold excess risk among black compared with white individuals in the United States
      is not reflected in the prevalence of less severe degrees of impaired kidney
      function among black compared with white individuals. The four-variable
      Modification of Diet in Renal Disease study equation was used to evaluate the
      black-to-white prevalence of impaired kidney function with increasing severity of
      impairment among participants in the Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) study, a nationally representative, population
      based cohort of individuals who are 45 yr and older. An estimated GFR (eGFR)<60
      ml/min per 1.73 m2 was present in 43.3% of the 20,667 REGARDS participants and
      was slightly less prevalent among black than white patients (33.7 versus 49.9%;
      prevalence odds ratio 0.51; 95% confidence interval [CI] 0.48 to 0.54). The lower
      prevalence among black patients was not uniform as eGFR declined. After
      controlling for other patient characteristics, the black-to-white odds ratio was
      0.42 (95% CI 0.40 to 0.46) at an eGFR of 50 to 59 ml/min per 1.73 m2 and
      increased to 1.73 (95% CI 1.02 to 2.94) at an eGFR of 10 to 19 ml/min per 1.73
      m2. The disparity in prevalence of impaired kidney function among white compared
      with black patients reversed as the severity of impaired kidney function
      increased. Factors that are responsible for the increasing prevalence of severely
      impaired kidney function among black patients remain to be determined.

PMID- 16641152
TI  - Role of EGF receptor activation in angiotensin II-induced renal epithelial cell
      hypertrophy.
AB  - For determination of the molecular mechanisms underlying the induction of
      epithelial cell hypertrophy by angiotensin II (Ang II), a well-characterized
      porcine renal proximal tubular cell line LLCPKcl4, which does not express
      endogenous Ang II receptor subtypes, was transfected with cDNA encoding Ang II
      subtype 1 receptor (AT1R/Cl4). Ang II transactivated the EGF receptor (EGFR) in
      these AT1R/Cl4 cells, which was blocked by the selective AT1R antagonist losartan
      but not by the selective AT2R antagonist PD123319. Ang II did not transactivate
      EGFR in empty vector-transfected LLCPKcl4 cells (Vector/Cl4). Ang II elicited
      release of soluble heparin-binding EGF-like growth factor (HB-EGF) from AT1R/Cl4
      cells, and Ang II-induced EGFR activation was prevented by pretreatment with the
      specific HB-EGF inhibitor CRM197 or the metalloproteinase inhibitors batimastat
      or phenanthroline, none of which had any effect on EGFR activation by exogenously
      administered EGF. Ang II stimulated protein synthesis and cell hypertrophy in
      AT1R/Cl4 cells without increasing cell number, and signaling studies revealed
      that Ang II stimulated phosphorylation of the 40S ribosomal protein S6 and the
      eukaryotic translation initiation factor 4E-binding protein 1, the two downstream
      target proteins of the mammalian target of rapamycin, which is a central
      regulator of protein synthesis and cell size. Ang II-induced mammalian target of
      rapamycin activation, [3H]leucine incorporation, and cellular hypertrophy were
      inhibited by pretreatment with either batimastat or CRM197 or by pretreatment
      with rapamycin or the EGFR tyrosine kinase inhibitor AG1478. Ang II also
      stimulated Smad 2/3 phosphorylation, which was blocked by a selective TGF-beta
      receptor I kinase inhibitor but not by CRM197. With blockade of TGF-beta
      receptor, Ang II-mediated hypertrophy was converted into cell proliferation,
      which was blocked by CRM197. In summary, this is the first demonstration that HB
      EGF shedding-dependent EGFR transactivation, along with activation of TGF-beta
      signaling pathways, mediates Ang II-induced renal tubular epithelial cell
      hypertrophy.

PMID- 16641153
TI  - Obesity and risk for chronic renal failure.
AB  - Few large-scale epidemiologic studies have quantified the possible link between
      obesity and chronic renal failure (CRF). This study analyzed anthropometric data
      from a nationwide, population-based, case-control study of incident, moderately
      severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr
      and had CRF and whose serum creatinine for the first time and permanently
      exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of
      926 case patients and 998 control subjects, randomly drawn from the study base,
      were enrolled. Face-to-face interviews, supplemented with self-administered
      questionnaires, provided information about anthropometric measures and other
      lifestyle factors. Logistic regression models with adjustments for several co
      factors estimated the relative risk for CRF in relation to body mass index (BMI).
      Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three
      fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and
      morbid obesity (BMI>or=35) among women anytime during lifetime was linked to
      three- to four-fold increases in risk. The strongest association was with
      diabetic nephropathy, but two- to three-fold risk elevations were observed for
      all major subtypes of CRF. Analyses that were confined to strata without
      hypertension or diabetes revealed a three-fold increased risk among patients who
      were overweight at age 20, whereas the two-fold observed risk elevation among
      those who had a highest lifetime BMI of >35 was statistically nonsignificant.
      Obesity seems to be an important-and potentially preventable-risk factor for CRF.
      Although hypertension and type 2 diabetes are important mediators, additional
      pathways also may exist.

PMID- 16641154
TI  - Extracellular signal-regulated kinase inhibition slows disease progression in
      mice with polycystic kidney disease.
AB  - The expression of mitogen-activated protein kinases (MAPK) in DBA/2-pcy/pcy (pcy)
      mice, a murine model of polycystic kidney disease was investigated. Proliferating
      cell nuclear antigen-positive cells were recognized in cyst epithelium from
      embryonic day 14.5 to 25 wk of age. Extracellular signal-regulated kinase (ERK)
      was expressed in the renal tubules of control and pcy mice, but stronger
      immunostaining was observed in cyst epithelium. Phosphorylated ERK was detected
      only in pcy mice and was localized predominantly in the cysts. p38 MAPK (p38) was
      no longer expressed after birth in controls but was detected in the cyst
      epithelium and in occasional tubular cells of pcy mice at all stages examined. c
      Jun N-terminal kinase (JNK) was expressed in all tubular segments of controls
      after neonatal day 7, whereas in pcy kidneys, tubules became positive for JNK
      after 8 wk, and the cysts expressed little JNK. Administration of an oral MAP/ERK
      kinase inhibitor, PD184352, 400 mg/kg per d, to 10-wk-old pcy mice daily for the
      first week and then every third day for 6 additional weeks significantly
      decreased BP, kidney weight, serum creatinine level, and water intake and
      significantly increased urine osmolality. The cystic index and expression of
      phosphorylated ERK and ERK were significantly lower in PD184352-treated pcy mice.
      These results demonstrate that the expression of MAPK is dysregulated in cyst
      epithelium and that inhibition of ERK slowed the progression of renal disease in
      pcy mice.

PMID- 16641155
TI  - Do we need to be cautious in evaluating suicide statistics?

PMID- 16641156
TI  - Influence of parental education, childhood adversities, and current living
      conditions on daily smoking in early adulthood.
AB  - AIMS: To assess the association of parental education, childhood living
      conditions and adversities with daily smoking in early adulthood and to analyse
      the effect of the respondent's own education, main economic activity, and current
      family structure on these associations. METHODS: The study is based on a
      representative two-stage cluster sample (N = 1894, participation rate 79%) of
      young adults aged 18-29, in 2000, in Finland. The outcome measure is daily
      smoking. RESULTS: Parental smoking and the respondent's own education had the
      strongest effects on daily smoking. If both parents of the respondent were
      smokers, then the respondent was most likely to be a smoker too (for men OR (odds
      ratio) = 3.01, for women OR = 2.41 after all adjustments). Young adults in the
      lowest educational category had a much higher risk of daily smoking than those in
      the highest category (OR = 5.88 for women, 4.48 for men). For women parental
      divorce (OR = 2.31) and current family structure also determined daily smoking.
      Parental education had a strong gradient in daily smoking and the effect appeared
      to be mediated largely by the respondent's own educational level. CONCLUSIONS:
      Childhood living conditions are strong determinants of daily smoking. Much of
      their influence seems to be mediated through current living conditions, which are
      also determined by childhood conditions. Determinants of smoking behaviour are
      developed throughout the life course. The findings stress the importance of the
      respondent's education and parental smoking as determinants of smoking behaviour.
      Our results support the notion that intervention on smoking initiation and
      cessation should be considered throughout the life course. Parental involvement
      in fostering non-smoking would be important.

PMID- 16641157
TI  - Trends in acceptance of euthanasia among the general public in 12 European
      countries (1981-1999).
AB  - BACKGROUND: We wanted to examine how the acceptance of euthanasia among the
      general public in Western Europe has changed in the last decades, and we wanted
      to look for possible explanations. METHODS: We analysed data from the European
      Values Surveys, held in 1981, 1990, and 1999-2000 in 12 West European countries.
      In each country, representative samples of the general public were interviewed
      using the same structured questionnaire in all countries. Euthanasia was
      explained in the questionnaires as 'terminating the life of the incurably sick'.
      RESULTS: A total of 46 199 respondents participated in the surveys. A significant
      increase in acceptance of euthanasia could be observed in all countries except
      (West) Germany. While the average increase in euthanasia acceptance was 22%, the
      increase was particularly obvious in Belgium, Italy, Spain, and Sweden. Although
      changes in several characteristics of respondents, such as decrease in religious
      beliefs, rising belief in the right to self-determination, and (to a lesser
      extent) rise in levels of education, were associated with growing acceptance of
      euthanasia, they could only partly explain the increase of euthanasia acceptance
      over the years. CONCLUSIONS: An increase of euthanasia acceptance among the
      general public took place over the last two decades in almost all West European
      countries, possibly indicating a growing support for personal autonomy regarding
      medical end-of-life decisions. If this trend continues, it is likely to increase
      the public and political debate about the (legal) regulation of euthanasia under
      certain conditions of careful medical practice in several West European
      countries.

PMID- 16641158
TI  - Use of health care services by ethnic minorities in The Netherlands: do patterns
      differ?
AB  - BACKGROUND: This article examines the nature of ethnic differences in health care
      utilisation by assessing patterns of use in addition to single service
      utilisation. METHODS: Data were derived from the Second Dutch National Survey of
      General Practice. A nationally representative sample of 104 general practices
      participated in this survey. Data on health and health service utilisation were
      collected through face-to-face interviews. Based on a random sample per practice,
      a total of 12 699 Dutch-speaking people were interviewed, regardless of ethnic
      background. An additional study among a random sample of 1339 people from the
      four largest minority groups in The Netherlands was conducted. These four groups
      comprised people from Turkey, Surinam, Morocco, and The Netherlands Antilles.
      Multilevel analyses were performed to investigate ethnic differences in health
      care utilisation, adjusting for socio-economic status, health status, and level
      of urbanisation. RESULTS: Differences in utilisation patterns were particularly
      marked for people with a Moroccan, Turkish, or Antillean background. Compared to
      the other groups, Surinamese were more likely to have had contact with any
      professional health care service. No evidence was found that the gate keeping
      role of general practitioners in The Netherlands functions less effectively among
      the ethnic minority groups as compared to the indigenous population. CONCLUSION:
      The analysis of patterns of utilisation proved to supply useful information
      concerning the relationship between ethnicity and use of health care services in
      addition to figures concerning single service use only.

PMID- 16641159
TI  - Exploring the relationship between development and road traffic injuries: a case
      study from India.
AB  - BACKGROUND: Road traffic injuries (RTI) are a major cause of mortality and
      disability in the world. Only after significant losses have communities in
      developed nations taken necessary steps to prevent crashes and their
      consequences. Increase in road safety is related to increasing socio-economic
      development. We aim to study the trends in injury and death rates in a developing
      country, India, define sub-national variations, and analyse these trends in
      relation to economic and population growth. METHODS: Public sector data from
      India were used to develop a standardized database on traffic injuries and
      indicator of economic development. The data were analysed using linear regression
      models to test the a priori hypothesis of a positive relationship between net
      domestic product (NDP), and injury and death rates from road crashes across
      states. RESULTS: The absolute burden of RTI in India has been consistently rising
      over the past three decades. The reported rates are lower than those estimated by
      global health agencies and may reflect under-reporting. Population-based rates
      provide a better assessment of the public health burden of RTI than vehicle-based
      rates. There is an inverted U-shaped relationship between NDP and injury and
      death rates. Even with the limited data, Kuznets phenomenon is evident for within
      country level comparisons. CONCLUSIONS: India and other developing countries
      could learn from the experience of highly motorized nations to avoid the expected
      rise in RTI and deaths with economic development, by currently investing in road
      safety and prevention measures.

PMID- 16641160
TI  - Fighting tuberculosis and HIV/AIDS in Northeast Europe: sustainable collaboration
      or political rhetoric?
AB  - BACKGROUND: In April 2000, the Council of the Baltic Sea States established the
      Task Force on Communicable Disease Control in the Baltic Sea region (the Task
      Force). A successor structure, the Northern Dimension Partnership in Public
      Health and Social Wellbeing, was established in autumn 2003. This article, a
      follow-up study to a series of evaluations of the Task Force evaluation, examines
      whether the Northern Dimension has succeeded in developing the achievements of
      the Task Force and ensuring the sustainability of regional health collaboration.
      METHODS: The study is qualitative, relying on documentary analysis and semi
      structured in-depth interviews with key actors. Relevant literature and key
      programme documents were consulted, and approximately 100 interviews were
      conducted. RESULTS: The short history of the Northern Dimension Partnership shows
      that many of the problems encountered in the Task Force are reappearing.
      Interstate rivalry, most prominent between Nordic countries, still hampers
      progress, with resulting scarce funding. The Partnership emphasizes the need to
      anchor future collaboration in centrally placed agencies in all participating
      countries. This is a time-consuming process, and has the inevitable effect of
      slowing down project work. CONCLUSION: Although epidemiological data clearly
      illustrate the need for continued multinational support to communicable disease
      control in Northeast Europe, the above-mentioned factors impede progress in this
      respect. While there are good reasons for cultivating partnerships with Russian
      federal agencies in terms of sustainability, this focus does represent a loss of
      momentum that may be difficult to overcome.

PMID- 16641161
TI  - Neighbourhood income and anxiety: a study based on random samples of the Swedish
      population.
AB  - BACKGROUND: Few studies have investigated the association between the
      neighbourhood characteristics and the vast panorama of mental disorders. This
      study examined whether there is an association between neighbourhood income and
      anxiety, a common mental disorder. METHODS: A national random sample of the
      entire Swedish population was used, consisting of 30 884 men and women aged 25-64
      years. The sample was obtained from pooled data during the period 1995-2002 from
      the Swedish Annual Level of Living Survey. Small area market statistics were used
      in order to define neighbourhoods. The proportion of individuals with incomes in
      the lowest national income quartile was calculated for each neighbourhood. The
      distribution was then divided into quartiles. A log binomial model was applied in
      the estimation of prevalence ratios. Four models were calculated with stepwise
      inclusion of the variables. Model 4 was adjusted for all the individual
      variables, i.e. age, gender, marital status, immigrant status, social network,
      housing tenure, employment status, and income. RESULTS: In neighbourhoods with
      the highest proportions of individuals with low income the prevalence ratio of
      anxiety was 1.33 (95% confidence interval 1.24-1.42). The association
      demonstrated between neighbourhood income and anxiety decreased after stepwise
      inclusion of the individual variables and disappeared after all the individual
      variables were accounted for. CONCLUSION: Compositional explanations, rather than
      contextual explanations, lie behind the association between neighbourhood income
      and anxiety, a common mental disorder. However, we do not exclude the possibility
      that there is a contextual effect on severe mental disorders or among children
      with behavioural problems.

PMID- 16641162
TI  - Perceived financial difficulties and maladjustment outcomes in adolescence.
AB  - BACKGROUND: Studies using traditional SES indicators in strictly adolescent
      populations have usually failed to find class differences in adolescent mental
      health. The present study aimed to find out whether there is an association
      between adolescent perceived financial difficulties of the family and adolescent
      maladjustment, and to explore the possible sex differences in this association.
      METHODS: School-based survey on 3278 ninth grade students (15-16 years old) in
      two economically well developed Finnish cities. RESULTS: One-fifth of the
      adolescents reported that their family had financial difficulties in the previous
      12 months. Perceiving financial difficulties was significantly more common among
      girls than boys. Perceived financial difficulties were associated with known risk
      factors of poverty and with depression and harmful drinking patterns in both
      sexes. Adjusting for parental educational levels, parental unemployment and
      family structure did not change the significant association with maladjustment
      outcomes. Additional adjustment with comorbidity, however, levelled out the
      significance of the association of perceived financial difficulties and harmful
      drinking patterns in boys. CONCLUSION: While adolescent perception of financial
      difficulties is probably associated with the objective financial situation of the
      family it may also be an indicator of the psychological meaning attached to the
      situation and should thus be considered a possible risk factor for adolescent
      maladjustment in clinical practice.

PMID- 16641163
TI  - Mobility and invasiveness of metastatic esophageal cancer are potentiated by
      shear stress in a ROCK- and Ras-dependent manner.
AB  - To metastasize, tumor cells must adopt different morphological responses to
      resist shear forces encountered in circulating blood and invade through basement
      membranes. The Rho and Ras GTPases play a critical role in regulating this
      dynamic behavior. Recently, we demonstrated shear-induced activation of adherent
      esophageal metastatic cells, characterized by formation of dynamic membrane
      blebs. Although membrane blebbing has only recently been characterized as a
      rounded mode of cellular invasion promoted through Rho kinase (ROCK), the role of
      shear forces in modulating membrane blebbing activity is unknown. To further
      characterize membrane blebbing in esophageal metastatic cells (OC-1 cell line),
      we investigated the role of shear in cytoskeletal remodeling and signaling
      through ROCK and Ras. Our results show that actin and tubulin colocalize to the
      cortical ring of the OC-1 cell under static conditions. However, under shear,
      actin acquires a punctuate distribution and tubulin localizes to the leading edge
      of the OC-1 cell. We show for the first time that dynamic bleb formation is
      induced by shear alone independent of integrin-mediated adhesion (P < 0.001,
      compared with OC-1 cells). Y-27632, a specific inhibitor of ROCK, causes a
      significant reduction in shear-induced bleb formation and inhibits integrin
      alpha(v)beta(3)-Ras colocalization at the leading edge of the cell. Direct
      measurement of Ras activation shows that the level of GTP-bound Ras is elevated
      in sheared OC-1 cells and that the shear-induced increase in Ras activity is
      inhibited by Y-27632. Finally, we show that shear stress significantly increases
      OC-1 cell invasion (P < 0.007), an effect negated by the presence of Y-27632.
      Together our findings suggest a novel physiological role for ROCK and Ras in
      metastatic cell behavior.

PMID- 16641164
TI  - Distinct K+ conductive pathways are required for Cl- and K+ secretion across
      distal colonic epithelium.
AB  - Secretion of Cl(-) and K(+) in the colonic epithelium operates through a cellular
      mechanism requiring K(+) channels in the basolateral and apical membranes.
      Transepithelial current [short-circuit current (I(sc))] and conductance (G(t))
      were measured for isolated distal colonic mucosa during secretory activation by
      epinephrine (Epi) or PGE(2) and synergistically by PGE(2) and carbachol (PGE(2) +
      CCh). TRAM-34 at 0.5 microM, an inhibitor of K(Ca)3.1 (IK, Kcnn4) K(+) channels
      (H. Wulff, M. J. Miller, W. Hansel, S. Grissmer, M. D. Cahalan, and K. G. Chandy.
      Proc Natl Acad Sci USA 97: 8151-8156, 2000), did not alter secretory I(sc) or
      G(t) in guinea pig or rat colon. The presence of K(Ca)3.1 in the mucosa was
      confirmed by immunoblot and immunofluorescence detection. At 100 microM, TRAM-34
      inhibited I(sc) and G(t) activated by Epi ( approximately 4%), PGE(2) (
      approximately 30%) and PGE(2) + CCh ( approximately 60%). The IC(50) of 4.0
      microM implicated involvement of K(+) channels other than K(Ca)3.1. The secretory
      responses augmented by the K(+) channel opener 1-EBIO were inhibited only at a
      high concentration of TRAM-34, suggesting further that K(Ca)3.1 was not involved.
      Sensitivity of the synergistic response (PGE(2) + CCh) to a high concentration
      TRAM-34 supported a requirement for multiple K(+) conductive pathways in
      secretion. Clofilium (100 microM), a quaternary ammonium, inhibited Cl(-)
      secretory I(sc) and G(t) activated by PGE(2) ( approximately 20%) but not K(+)
      secretion activated by Epi. Thus Cl(-) secretion activated by physiological
      secretagogues occurred without apparent activity of K(Ca)3.1 channels but was
      dependent on other types of K(+) channels sensitive to high concentrations of
      TRAM-34 and/or clofilium.

PMID- 16641165
TI  - Regulation of UT-A1-mediated transepithelial urea flux in MDCK cells.
AB  - Transepithelial [(14)C]urea fluxes were measured across cultured Madin-Darby
      canine kidney (MDCK) cells permanently transfected to express the urea transport
      protein UT-A1. The urea fluxes were typically increased from a basal rate of 2 to
      10 and 25 nmol.cm(-2).min(-1) in the presence of vasopressin and forskolin,
      respectively. Flux activation consisted of a rapid-onset component of small
      amplitude that leveled off within approximately 10 min and at times even
      decreased again, followed by a delayed, strong increase over the next 30-40 min.
      Forskolin activated urea transport through activation of adenylyl cyclase;
      dideoxyforskolin was inactive. Vasopressin activated urea transport only from the
      basolateral side and was blocked by OPC-31260, indicating that its action was
      mediated by basolateral V(2) receptors. In the presence of the phosphodiesterase
      inhibitor IBMX, vasopressin activated as strongly as forskolin. By itself, IBMX
      caused a slow increase over 50 min to approximately 5 nmol.cm(-2).min(-1). 8
      Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 300 microM) activated urea
      flux only when added basolaterally. IBMX augmented the activation by basolateral
      8-BrcAMP. Urea flux activation by vasopressin and forskolin were only partially
      blocked by the protein kinase A inhibitor H-89. Even at concentrations >10
      microM, urea flux after 60 min of stimulation was reduced by <50%. The rapid
      onset component appeared unaffected by the presence of H-89. These data suggest
      that activation of transepithelial urea transport across MDCK-UT-A1 cells by
      forskolin and vasopressin involves cAMP as a second messenger and that it is
      mediated by one or more signaling pathways separate from and in addition to
      protein kinase A.

PMID- 16641166
TI  - Wide variety of locations for rodent MATE1, a transporter protein that mediates
      the final excretion step for toxic organic cations.
AB  - MATE1 was the first mammalian example of the multidrug and toxin extrusion (MATE)
      protein family to be identified. Human MATE1 (hMATE1) is predominantly expressed
      and localized to the luminal membranes of the urinary tubules and bile canaliculi
      and mediates H(+)-coupled electroneutral excretion of toxic organic cations (OCs)
      into urine and bile (Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, and
      Moriyama Y. Proc Natl Acad Sci USA 102: 17923-17928, 2005). mMATE1, a mouse MATE
      ortholog, is also predominantly expressed in kidney and liver, although its
      transport properties are not yet characterized. In the present study, we
      investigated the transport properties and localization of mMATE1. Upon expression
      of this protein in HEK-293 cells, mMATE1 mediated electroneutral
      H(+)/tetraethylammonium exchange and showed a substrate specificity similar to
      that of hMATE1. Immunological techniques with specific antibodies against mMATE1
      combined with RT-PCR revealed that mMATE1 is also expressed in various cells,
      including brain glia-like cells and capillaries, pancreatic duct cells, urinary
      bladder epithelium, adrenal gland cortex, alpha cells of the islets of
      Langerhans, Leydig cells, and vitamin A-storing Ito cells. These results indicate
      that mMATE1 is a polyspecific H(+)/OC exchanger. The unexpectedly wide
      distribution of mMATE1 suggests involvement of this transporter protein in
      diverse biological functions other than excretion of OCs from the body.

PMID- 16641167
TI  - Aromatase expression in endometriotic tissues and cell cultures of patients with
      endometriosis.
AB  - Cytochrome P-450 aromatase is responsible for catalysing the conversion of
      androstendione into estrone, so its expression in endometriotic tissue could
      contribute to the development of endometriosis. The aims of this study were, on
      the one hand, to determine the presence of aromatase in eutopic and ectopic
      endometrium, healthy peritoneum, myometrium and leiomyomas from patients with (n
      = 61) and without endometriosis (n = 12) and, on the other hand, to determine the
      effect of peritoneal fluid (PF), interleukin-6 (IL-6) and tumour necrosis factor
      alpha (TNFalpha) on aromatase activity from endometriotic stromal cells and
      subcutaneous adipocytes. After immunohistochemical analysis, aromatase expression
      was detected in the endometriotic tissue of 61% of patients, whereas the rest of
      the tissues, as well as those from disease-free women, were negative. Cell
      cultures were made to determine aromatase activity in endometriotic stromal cells
      and adipocytes. The addition of PF, TNFalpha and especially IL-6 (P < 0.05)
      stimulated the basal enzymatic activity observed in both cell types. Our findings
      confirm the presence of aromatase in endometriosis and probably the existence of
      a local estrogen production that may be stimulated by some factors such as
      cytokines present in the PF of these patients. Therefore, the use of aromatase
      inhibitors combined with immunomodulator agents could be a novel approach to be
      investigated in future clinical trials.

PMID- 16641168
TI  - Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the
      treatment of patients with advanced pancreatic cancer: results of a phase II
      randomized, double-blind, placebo-controlled, multicenter study.
AB  - BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic
      activity and synergism with gemcitabine preclinically. This randomized phase II
      trial explored whether CI-994 plus gemcitabine improves overall survival,
      objective response, duration of response, time to treatment failure and change in
      quality of life (QoL) or pain compared with gemcitabine alone. PATIENTS AND
      METHODS: A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus
      gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus
      gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21).
      RESULTS: Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The
      objective response rate with CG was 12% versus 14% with PG when investigator
      assessed and 1% versus 6%, respectively, when assessed centrally. Time to
      treatment failure did not differ between the two arms (P = 0.304). QoL scores at
      2 months were worse with CG than with PG. Pain response rates were similar
      between the two groups. There was an increased incidence of neutropenia and
      thrombocytopenia with CG. CONCLUSIONS: Adding CI-994 to gemcitabine in advanced
      pancreatic carcinoma does not improve overall survival, response rate or time to
      progression; CG produced decreased QoL and increased hematological toxicity and
      appears inferior to single-agent gemcitabine.

PMID- 16641169
TI  - Buprenorphine-induced acute respiratory depression during ifosfamide-based
      chemotherapy.

PMID- 16641170
TI  - Measuring tumor response and shape change on CT: esophageal cancer as a paradigm.
AB  - BACKGROUND: Accurate response assessment is essential for evaluating new cancer
      treatments. We evaluated the impact of Response Evaluation Criteria in Solid
      Tumors (RECIST), World Health Organization (WHO) criteria and tumor shape on
      response assessment in patients with metastatic esophageal cancer. PATIENTS AND
      METHODS: In 19 patients with metastatic esophageal cancer in a phase II trial of
      bryostatin-1 and paclitaxel, response was retrospectively assessed for 89 lesions
      with RECIST and WHO criteria on baseline and serial follow-up CT scans. The
      eccentricity factor (EF) was introduced for measuring the degree to which tumor
      shape diverges from a perfect sphere [EF = radical1-(LPD/MD)(2), where LPD is the
      largest perpendicular diameter and MD is the maximal diameter]. RESULTS: The
      disagreement rate in best overall response categorization between RECIST
      (unidimensional) and WHO (bidimensional) criteria was 26.3%. Change in
      eccentricity was significantly greater (P < 0.01) for patients with disagreement
      (mean 0.31, range 0-0.91). When the short axis was used for unidimensional lymph
      node measurement, disagreement between WHO and RECIST lessened. CONCLUSIONS:
      Response assessment by WHO and RECIST differs substantially. Greater change in
      eccentricity is associated with greater discordance between WHO and RECIST. The
      discordance between WHO and RECIST may impact on how effective a therapy is
      judged to be.

PMID- 16641171
TI  - Determinants of older adults' intentions to vaccinate against influenza: a
      theoretical application.
AB  - BACKGROUND: Despite many government initiatives, uptake of the trivalent
      influenza vaccine among the older adult population still remains suboptimal. If
      immunization rates are to be optimized, new approaches for identifying the
      determinants that facilitate or inhibit influenza vaccination decision making in
      this population are necessary. METHODS: An extension of the theory of planned
      behaviour (TPB) provided the theoretical framework for the development of a multi
      item questionnaire. One hundred and ninety-three white, independent living and
      city dwelling men (n =77) and women (n = 116), completed the measure. The main
      outcomes of interest were future vaccination intentions. RESULTS: Overall, the
      TPB predicted 48.2% of older adults' intentions to vaccinate next influenza
      season. Receiving the vaccine in the past and anticipating feelings of regret
      (the impact of missing a vaccination opportunity) contributed to increments of
      10.7 and 13.7%, respectively, in explaining this intentional behaviour.
      CONCLUSION: Utility of theoretical frameworks is a useful resource tool for
      understanding the rationale behind the facilitating and inhibitory determinants
      of older adults' vaccination decision-making processes. The implications of this
      research are discussed with a view towards future directions for maximizing
      influenza vaccination uptake initiatives using theoretically driven applications.

PMID- 16641172
TI  - Rationalizing rationing in health care: experience of two primary care trusts.
AB  - BACKGROUND: Priority setting, or rationing, in healthcare is an unavoidable
      consequence of competing demands on the resources available. This is a
      description of the experience of the two Primary Care Trusts in using an explicit
      scoring tool to prioritize proposals submitted for new funding within the local
      health economy. METHODS: A Priorities Forum Panel was established, comprising
      representatives from the local NHS trusts. The Panel reviewed and scored new
      funding proposals and then ranked them for priority funding. RESULTS: Over 100
      proposals were submitted (total cost: approximately 44 million pounds). Sixty-six
      proposals were scored (total cost: over 26 million pounds). Around 5 million
      pounds was available for funding, resulting in few of the top-scoring proposals
      being supported. The proposals which were linked to the implementation of
      National Institute for Health and Clinical Excellence (NICE) guidance were
      generally given a lower priority compared with those likely to relieve local
      pressures and facilitate the implementation of specific National Service
      Framework criteria. CONCLUSIONS: Funding of the locally driven priorities took
      precedence over some of the nationally driven priorities, such as funding of
      specific NICE guidance. The shortfall in resources did not allow for the funding
      of a significant number of high-scoring proposals.

PMID- 16641173
TI  - Using multiple sources to improve and measure case ascertainment in surveillance
      studies: 20 years of the British Paediatric Surveillance Unit.
AB  - BACKGROUND: The British Paediatric Surveillance Unit (BPSU) was established in
      1986 to facilitate national surveillance of uncommon paediatric disorders. This
      study investigated the effectiveness of using multiple source reporting and
      capture-recapture analysis to maximize case ascertainment in studies undertaken
      through the BPSU. METHODS: Structured review of all surveillance studies
      completed through the BPSU. Quantitative and qualitative analysis of the
      effectiveness of multiple reporting sources and capture-recapture methods was
      made. RESULTS: Of 71 studies undertaken through the BPSU, 59 were included in
      this review and 38 used additional data sources. Established national sources
      were most readily adapted for use as secondary data sources, including routine
      health data, communicable disease and specialty-specific surveillance units,
      whilst the involvement of parent groups and the media was less successful. Six
      studies employed capture-recapture techniques to estimate the completeness of
      case ascertainment. CONCLUSIONS: Active surveillance through the BPSU remains a
      timely and reliable primary source of cases, but employing additional reporting
      sources is effective in enhancing case ascertainment. When the assumptions for
      its valid use are met, capture-recapture analysis allows the estimation of
      completeness of ascertainment. It is essential to define the purpose of an
      additional source at the outset of a study and to ensure that subsequent analysis
      is appropriate.

PMID- 16641196
TI  - Hsp90 increases LIM kinase activity by promoting its homo-dimerization.
AB  - LIM kinase 1 (LIMK1) is a serine protein kinase that regulates the actin
      cytoskeleton by phosphorylation and inactivation of actin depolymerizing factor
      cofilin. LIMK1 activity is regulated by the Rho-GTPases via their
      serine/threonine kinase effectors Rho-kinase and p21-activated kinases 1 and 4
      that phosphorylate LIMK1 on threonine 508 in its activation loop. The purpose of
      this study was to elucidate the pathway leading to the stability of LIMK1, a
      protein with a half-life of approximately 20 h. Because the half-life of kinase
      dead LIMK1 is only 4 h, it is suggestive that trans- or auto-phosphorylation is
      responsible for the stabilization of LIMK1. Using known Hsp90 inhibitors, we have
      shown that the half-life of LIMK1 in cells depends on the presence of active
      Hsp90. Furthermore, endogenous LIMK1 coimmunoprecipitated with endogenous Hsp90
      and this interaction promoted LIMK1 homodimer formation as seen by cross-linking
      experiments. Hsp90 binds LIMK1 via a recognition sequence within the LIMK1 kinase
      domain, homologous to that of ErbB-2. Mutation of a proline residue within this
      sequence to glutamic acid reduces its interaction with Hsp90, inhibits homodimer
      formation, and reduces its half-life to 4 h. These findings implicate Hsp90 in
      the stabilization of LIMK1 by promoting homodimer formation and
      transphosphorylation.

PMID- 16641197
TI  - Identification and characterization of riproximin, a new type II ribosome
      inactivating protein with antineoplastic activity from Ximenia americana.
AB  - The aim of this study was to identify and characterize the active component(s) of
      Ximenia americana plant material used to treat cancer in African traditional
      medicine. By a combination of preextraction, extraction, ion exchange and
      affinity chromatography, a mixture of two cytotoxic proteins was isolated. Using
      degenerated primers designed on the de novo sequence of two tryptic peptides from
      one of these proteins, a DNA fragment was amplified and the sequence obtained was
      used to determine the complete cDNA sequence by the RACE method. Sequence
      analysis and molecular modeling showed that the new protein, riproximin, belongs
      to the family of type II ribosome inactivating proteins. These results are in
      good agreement with the ability of riproximin to inhibit protein synthesis in a
      cell-free system, as well as with the cytotoxicity of riproximin, as demonstrated
      by its IC50 value of 0.5 pM in MCF7, 1.1 pM in HELA and 0.6 pM in CC531-lacZ
      cells. To assess the antineoplastic efficacy of the purified riproximin in vivo,
      the CC531-lacZ colorectal cancer rat metastasis model was used. Significant
      anticancer activity was found after administration of total dosages of 100
      (perorally) and 10 (intraperitoneally) pmol riproximin/kg. These results suggest
      that riproximin has distinct potential for cancer treatment.

PMID- 16641198
TI  - The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective
      activity and induces blood brain barrier permeability after focal cerebral
      ischemia.
AB  - Based on its trophic influence on neurons and vascular cells, vascular
      endothelial growth factor (VEGF) is a promising candidate for stroke treatment.
      VEGF's survival-promoting effects are purchased at the expense of an increased
      blood brain barrier permeability, which potentially compromises tissue survival.
      The mechanisms via which VEGF protects the brain against ischemia remained
      unknown. We examined signaling pathways underlying VEGF's neuroprotective
      activity in our transgenic mouse line, which expresses human VEGF165 under a
      neuron-specific enolase (NSE) promoter. We show that VEGF receptor-2 (Flk-1) is
      expressed on ischemic neurons and astrocytes and is activated by VEGF. Following
      90-min episodes of middle cerebral artery occlusion, VEGF increased
      phosphorylated (but not total) Akt and ERK-1/-2 and reduced phosphorylated
      mitogen activated protein kinase/p38 and c-Jun NH2-terminal kinase (JNK)-1/-2
      levels, at the same time decreasing inducible NO synthase expression in ischemic
      neurons. Inhibition of Akt with Wortmannin reversed VEGF's neuroprotective
      properties, diminished brain swelling, and restored the vascular permeability
      induced by VEGF to below levels in WT animals. The aggravation of brain injury by
      Wortmannin was associated with the restitution of p38, but not of JNK-1/-2, ERK
      1/-2, or inducible NOS (iNOS). Our data demonstrate that VEGF mediates both
      neuroprotection and blood brain barrier permeability via the phosphatidylinositol
      3 kinase (PI3K)/Akt pathway. Based on our observation that VEGF neuroprotection
      and vascular leakage depend on PI3K/Akt, which is putatively regulated by VEGF
      receptor-2, we predict that it may not easily be possible to make use of VEGF's
      neuroprotective function without accepting its unfavorable consequence, the
      increased vascular permeability.

PMID- 16641199
TI  - HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S
      phase re-entry in stressed cells.
AB  - Stress-inducible HSP27 protects cells from death through various mechanisms. We
      have recently demonstrated that HSP27 can also enhance the degradation of some
      proteins through the proteasomal pathway. Here, we show that one of these
      proteins is the cyclin-dependent kinase (Cdk) inhibitor p27Kip1. The
      ubiquitination and degradation of this protein that favors progression through
      the cell cycle was previously shown to involve either a Skp2-dependent
      mechanism,i.e., at the S-/G2-transition, or a KPC (Kip1 ubiquitination-promoting
      complex)-dependent mechanism, i.e.,at the G0/G1 transition. In this work, we
      demonstrate that, in response to serum depletion, p27Kip1 cellular content first
      increases then progressively decreases as cells begin to die. In this stressful
      condition, HSP27favors p27Kip1 ubiquitination and degradation by the proteasome.
      A similar observation was made in response to stress induced by the NO donor
      glyceryl trinitrate (GTN). HSP27-mediated ubiquitination ofp27Kip1 does not
      require its phosphorylation on Thr187 or Ser-10, nor does it depend on the
      SCFSkp2 ubiquitin ligase E3 complex. It facilitates the G1/S transition,which
      suggests that, in stressful conditions, HSP27might render quiescent cells
      competent to re-enter the cell cycle.

PMID- 16641200
TI  - Type-I but not type-II interferon receptor knockout mice are susceptible to
      biliary atresia.
AB  - The etiology of biliary atresia (BA) is not yet understood, but recent studies
      have shown inflammation with an up-regulated interferon (IFN) activity in the
      intra- and extrahepatic bile ducts of patients with BA. These findings support an
      inflammatory/infectious cause of BA as mimicked in our infective murine model. To
      study the role of the IFN receptors in our model, we used mice with inactivated
      INF-alpha/beta receptor A129, with inactivated IFN-gamma receptor G129, or
      inactivation of both interferon receptors AG129 as well as the wild type controls
      W129. Mice were infected with rotavirus within 48h of birth and 7 d postpartum.
      The incidence of BA in each group was determined during a 3 wk period. In the
      second week the virus load was measured. BA incidence was 76% in A129 and 67% in
      AG129 animals, whereas in the G129 group only 33% of the pups developed BA. The
      wild type presented with a BA-incidence of 15%, while 7 d old mice failed to
      develop BA. There was no significant difference in the virus load of the livers
      between the groups independent of clinical symptoms. In conclusion, inactivation
      of type I INF-receptor significantly increases the incidence of BA following
      postpartal rotavirus infection. This effect is independent of the presence of
      type II-INF-receptors. Thus, in our model a type I IFN-linked deregulation of the
      innate immune system appears to be crucial for the induction of biliary atresia.

PMID- 16641201
TI  - Effect of intravenous sildenafil on pulmonary hemodynamics and gas exchange in
      the presence and absence of acute lung injury in piglets.
AB  - Sildenafil is becoming increasingly popular for the treatment of pulmonary
      hypertension. However, there are potential concerns regarding its effects on
      oxygenation and systemic hemodynamics that could theoretically reduce its utility
      in the neonatal population. We performed a prospective cumulative dose-response
      study of increasing doses of i.v. sildenafil (0.4, 1, and 3 mg/kg) on
      hemodynamics and oxygenation in 32 anesthetized piglets, of which 17 had meconium
      induced pulmonary hypertension and lung injury, and 15 did not. Sildenafil caused
      a reduction in mean pulmonary artery pressure and pulmonary vascular resistance
      (PVR) at all doses, in non-lung-injured animals. There was no difference in
      pulmonary hemodynamics between doses. Oxygenation index [OI = mean airway
      pressure (cm H2O) * FiO2 * 100/PaO2 (mm Hg)] did not reach critical levels at any
      dose. In lung-injured animals, sildenafil also reduced mean pulmonary artery
      pressure and PVR by 30%. Again, this effect was achieved at the lowest dose,
      without subsequent changes at higher doses. However, in lung-injured animals,
      sildenafil produced a dose-related increase in oxygenation index. Sildenafil
      reduced the systemic vascular resistance (SVR) at the lowest dose in lung-injured
      animals, but this occurred only at higher doses in non-lung-injured animals. In
      conclusion, sildenafil is a potent pulmonary vasodilator. However, it should be
      administered with caution in the presence of lung injury because of a dose
      related increase in oxygenation index and concomitant systemic vasodilatation.

PMID- 16641202
TI  - A new intronic mutation in the DPM1 gene is associated with a milder form of CDG
      Ie in two French siblings.
AB  - Congenital disorders of glycosylation (CDG) type I (CDG I) are rare autosomal
      recessive diseases caused by deficiencies in the assembly of the dolichol-linked
      oligosaccharide (DLO) that is required for N-glycoprotein biosynthesis. CDG Ie is
      due to a defect in the synthesis of dolichyl-phosphoryl-mannose (Dol-P-Man),
      which is needed for DLO biosynthesis as well as for other glycosylation pathways.
      Human Dol-P-Man synthase is a heterotrimeric complex composed of DPM1p, DPM2p,
      and DPM3p, with DPM1p being the catalytic subunit. Here, we report two new CDG Ie
      patients who present milder symptoms than the five other CDG Ie patients
      described to date. The clinical pictures of the patients MS and his sister MT are
      dominated by major ataxia, with no notable hepatic involvement. MS cells
      accumulate the immature DLO species Dol-PP-GlcNAc2Man5 and possess only residual
      Dol-P-Man synthase activity. One homozygous intronic mutation, g.IVS4-5T>A, was
      found in the DPM1 gene, leading to exon skipping and transcription of a shortened
      transcript. Moreover, DPM1 expression was reduced by more than 90% in MS cells,
      in a nonsense-mediated mRNA decay (NMD)-independent manner. Full analysis of the
      DPM2 and DPM3 genes revealed a decrease in DPM2 expression and normal expression
      of DPM3. This description emphasizes the large spectrum of symptoms
      characterizing CDG I patients.

PMID- 16641203
TI  - Expandable right ventricular-to-pulmonary artery conduit: an animal study.
AB  - This study was performed to assess a new vascular stent graft as an expandable
      valved conduit for right ventricular outflow tract (RVOT) reconstruction in
      sheep. Conduits were constructed by sewing an 18-mm valved conduit inside a
      stent. Crimped to 16 mm, they were implanted either under or without
      extracorporeal circulation in seven (group A) and in five (group B) sheep,
      respectively. Six weeks and 3 mo after their insertion, conduits were dilated
      intraluminally. A valved stent was implanted percutaneously into conduits before
      they were killed. Two animals from group A recovered normally, whereas five
      animals had a complicated postoperative course. In group B, one died acutely due
      to kinking of the conduit. Balloon dilatations were performed in all surviving
      animals. First dilatations had a slight impact on valvular function in all
      animals but one, whereas second dilatations led to significant PR in all.
      Transcatheter valve implantation was performed successfully. When animals were
      killed, no bleeding was found around the surgically implanted device. In
      conclusion, we designed a biologic valved conduit for RVOT reconstruction that
      can be dilated sequentially to follow animal growth. This new device can have
      tremendous applications in children with congenital heart diseases involving the
      RVOT.

PMID- 16641204
TI  - Are adolescent boys with Klinefelter syndrome androgen deficient? A longitudinal
      study of Finnish 47,XXY boys.
AB  - Testosterone (T)-substitution therapy is widely used in adult patients with
      Klinefelter syndrome (KS) to prevent symptoms and sequels of androgen deficiency,
      but it is currently unknown if adolescent boys with KS benefit from early T
      therapy. To evaluate the optimal age to start T substitution, we searched for
      signs of androgen deficiency in pubertal boys with KS. 14 nonmosaic 47,XXY boys,
      aged 10-13.9 y, were followed up for 4-37 mo with staging of puberty and frequent
      reproductive hormone measurements. Furthermore, indices reflecting androgen
      action (serum SHBG, leptin, and prostate-specific antigen (PSA) levels) were
      studied. Both onset and progression of puberty according to Tanner stages were
      normal in boys with KS. Consistently, serum T concentrations increased as
      expected and remained normal throughout follow-up. Changes in the indices of
      androgen action (decreases in serum SHBG and leptin, and increase in serum PSA
      concentrations) occurred normally, except that average leptin levels were higher
      in the boys with KS (KS boys 11.8 +/- 7.0 microg/L; controls 7.6 +/- 4.7
      microg/L; p = 0.033). Despite normal T concentrations, the KS boys displayed from
      the age of 13 y elevated serum FSH and LH levels, and exaggerated gonadotropin
      responses to gonadotropin-releasing hormone. These data do not demonstrate an
      unequivocal androgen deficiency in adolescent boys with KS that would necessitate
      androgen supplementation therapy during early puberty.

PMID- 16641205
TI  - Surfactant composition and function in patients with ABCA3 mutations.
AB  - Mutations in the gene encoding the ATP binding cassette transporter member A3
      (ABCA3) are associated with fatal surfactant deficiency. ABCA3 lines the limiting
      membrane of lamellar bodies within alveolar type-II cells, suggesting a role in
      surfactant metabolism. The objective of this study was to determine the
      surfactant phospholipid composition and function in patients with mutations in
      the ABCA3 gene. Bronchoalveolar lavage (BAL) fluid was analyzed from three groups
      of infants: 1) Infants with ABCA3 mutations, 2) infants with inherited surfactant
      protein-B deficiency (SP-B), and 3) patients without parenchymal lung disease
      (CON). Surfactant phospholipid profile was determined using two-dimensional thin
      layer chromatography, and surface tension was measured with a pulsating bubble
      surfactometer. Phosphatidylcholine comprised 41 +/- 19% of the total phospholipid
      in the BAL fluid of the ABCA3 group compared with 78 +/- 3% and 68 +/- 18%, p =
      0.008 and 0.05, of the CON and SP-B groups, respectively. Surface tension was
      31.5 +/- 9.3 mN/m and was significantly greater than CON but no different from SP
      B. We conclude that mutations in ABCA3 are associated with surfactant that is
      deficient in phosphatidylcholine and has decreased function, suggesting that
      ABCA3 plays an important role in pulmonary surfactant phospholipid homeostasis.

PMID- 16641206
TI  - Effect of orthotopic liver transplantation (OLT) on branched-chain amino acid
      requirement.
AB  - Little is known regarding the impact of liver transplantation on amino acid
      requirements in children. Since plasma levels of the branched-chain amino acids
      (BCAA) are decreased in the presence of normal levels of the aromatic amino acids
      after liver transplantation, normalization of hepatic function may not fully
      correct changes in BCAA metabolism that occur in the pretransplant period. The
      goal of the present study was to determine total BCAA requirements of children
      following liver transplantation. The requirement of total BCAA was determined
      using indicator amino acid oxidation (IAAO) in five clinically stable children
      (5.7 +/- 3.5 y, mean +/- SD) 1-8 y post liver transplantation. Children received
      in random order 6 graded intakes of total BCAA. Individual BCAA in the test diet
      were provided in the same proportions as present in egg protein to minimize the
      potential interactive effects of individual BCAA on assessment of requirement.
      Total BCAA requirement was determined by measuring the oxidation of L-[1-13C]
      phenylalanine to 13CO2 [F13CO2 in micromol/kg/h], after a primed, continuous
      infusion of the tracer and using a two-phase linear regression crossover
      regression analysis. The estimated average requirement and the upper limit of the
      95% CI for total BCAA in children who have undergone liver transplantation were
      172 and 206 mg/kg/d), respectively. Total BCAA requirement in children who have
      undergone orthotopic liver transplantation (OLT) remain increased in the post
      liver transplant period when compared with healthy school aged children, but is
      decreased when compared with children with mild-moderate chronic cholestatic
      (MCC) liver disease.

PMID- 16641207
TI  - Developmental regulation of GTP-CH1 in the porcine lung and its relationship to
      pulmonary vascular relaxation.
AB  - Nitric oxide (NO) plays an important role in lowering pulmonary vascular
      resistance after birth. However, in persistent pulmonary hypertension of the
      newborn (PPHN) NO-mediated dilation is dysfunctional. GTP-cyclohydrolase 1 (GTP
      CH1) is the rate-limiting enzyme for the biosynthesis of 6R-L-erythro-5,6,7,8
      tetrahydrobiopterin (BH4) an essential cofactor for nitric oxide synthase (NOS)
      activity. Suboptimal levels of BH4 may result in NOS uncoupling and the
      subsequent generation of harmful superoxide anions. We therefore investigated the
      functional effects of supplementing BH4 and/or a superoxide dismutase mimetic
      (MnTMPyP) in porcine intrapulmonary arteries from normal animals and from a
      porcine model of PPHN. We investigated whether any functional effects of BH4
      could be explained by changes in GTP-CH1 expression. Supplementation of BH4
      significantly improved endothelium-dependent relaxations in arteries from 3- and
      14-d-old healthy animals, whereas no effect was seen in vessels from younger
      animals and adults. GTP-CH1 protein expression was lowest at 3 and 14 d,
      suggesting a rate limitation of BH4 at this time. BH4 supplementation alone did
      not improve the relaxant response to acetylcholine in arteries obtained in a
      porcine model of PPHN. Furthermore, GTP-CH1 protein expression was normal for
      age. However, co-treatment with both BH4 and MnTMPyP restored endothelial
      function. GTP-CH1 is developmentally regulated in the pulmonary vasculature of
      neonates and this results in a functionally significant limitation of BH4.
      Although GTP-CH-1/BH4 levels alone do not explain the profound endothelial
      dysfunction seen in PPHN, increasing NO bioavailability by supplementing BH4 and
      quenching superoxide may prove to be therapeutically beneficial.

PMID- 16641208
TI  - Gender-related changes in magnetocardiographically determined fetal cardiac time
      intervals in intrauterine growth retardation.
AB  - Prenatal growth deficiencies as well as gender have been associated with
      cardiovascular disease in later life. It is also known that the duration of fetal
      cardiac time intervals (CTI) are dependent on fetal development. The aim of this
      work was to examine the relationship between fetal CTI in healthy and
      intrauterine growth retardation (IUGR) fetuses, taking gender into account. A
      total of 269 magnetocardiograms (MCG) were obtained in 47 healthy and 27 IUGR
      pregnancies. In each signal-averaged MCG, durations of CTI were determined. Age-
      and heart rate-corrected values were compared between normal and IUGR fetuses
      separately with respect to gender. Overall, there was an association between
      atrial and ventricular conduction times and estimated fetal body weight. In
      female fetuses, IUGR was associated with shorter P WAVE, PQ segment, PR interval,
      and QRS complex and longer STT and QT intervals. For males, this was so only for
      P wave, QRS complex, and STT interval. The shortening of conduction times in IUGR
      may be explained by reduced cardiac muscle mass associated with lower body
      weight. On the other hand, the gender-specific differences, particularly in the
      IUGR fetuses may be due to hormonal factors.

PMID- 16641209
TI  - Hepatoma-derived growth factor is expressed after vascular injury in the rat and
      stimulates smooth muscle cell migration.
AB  - The role of hepatoma-derived growth factor (HDGF), a novel nuclear-targeted
      vascular smooth muscle cell (SMC) mitogen in vascular injury is unknown. We
      hypothesized that HDGF plays a role in SMC proliferation and migration in
      formation of the neointima after balloon injury of the rat carotid. Using co
      immunohistochemical staining, HDGF and proliferating cell nuclear antigen (PCNA)
      were co-expressed in 80% of nuclei of neointimal cells 7 d post carotid balloon
      injury with HDGF. The HDGF-positive medial and neointimal cells were smooth
      muscle actin negative and therefore likely represented a subgroup of SMC that
      have undergone phenotypic switching. Utilizing modified Boyden chamber migration
      assays, adenoviral-expressed HDGF in mouse SMC increased migration 10-fold (20
      versus 2). HDGF gene silencing reduced both SMC proliferation and migration. In
      conclusion, HDGF is highly expressed in the media and neointima post balloon
      injury, a SMC mitogen and positive regulator of cell migration. We speculate that
      HDGF is involved in the SMC proliferative and migratory response to injury
      resulting in neointimal formation.

PMID- 16641210
TI  - The expression of CD40 on monocytes of children with primary humoral
      immunodeficiencies.
AB  - The interactions between CD40 and CD40L (CD154) are critical for effective
      humoral immune response. CD40 signaling facilitates T lymphocyte dependent B cell
      proliferation and immunoglobulin isotype switch. The objective of our study was
      to investigate the CD40 and CD40L expression on peripheral blood mononuclear
      cells (PBMC) of children with symptomatic transient hypogammaglobulinemia (THI),
      common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD).
      Additionally we studied the production of IL-12 and IL-18 by PBMC stimulated with
      soluble CD40L. CD40 expression was analyzed on B cells and monocytes, CD40L on
      activated T lymphocytes, using flow cytometry following staining of the cells
      with appropriate MAb. We found that CD40 expression on B cells and CD40L on
      activated T cells were essentially similar in the control and patient groups,
      while the decreased CD40 expression on monocytes was observed in THI and SIgAD
      patients compared with normal subjects. The most significant decrease of CD40
      expression was observed in THI (37% of positive cells) in comparison with control
      (81% of positive cells). IL-12, but not IL-18, release by PBMC was increased in
      THI and CVID, but not in SIgAD. In conclusion we suggest that the decreased
      expression of CD40 on monocytes of children with THI and SIgAD, but not CVID, may
      be involved in the pathomechanism of these immunodeficiencies.

PMID- 16641211
TI  - Associations of birth defects with adult intellectual performance, disability and
      mortality: population-based cohort study.
AB  - Infants born with birth defects have poorer outcomes in terms of mortality and
      disability, but the long-term intellectual outcome in children with birth defects
      is generally unknown. We assessed the long-term associations of various birth
      defects with mortality and disability, and evaluated whether high mortality and
      disability were reflected in impaired intellectual performance at age 18. In this
      nationwide cohort study, records of 9,186 males with and 384,384 without birth
      defects, registered in the Medical Birth Registry of Norway (1967-1979) were
      linked to the National Conscript Service (1984-1999). Mortality and disability
      before military draft, and intelligence test score at conscription were the main
      outcome measures. Males with birth defects had a relative risk for disability of
      6.0 compared with males without defects. Disability was low within categories of
      birth defects associated with low mortality, and high within defect categories
      associated with high mortality. The relative risk for not being drafted was
      highest if maternal educational level was low. Heart defects and cleft palate
      were the only subgroups in which intellectual performance was lower after
      adjustment for maternal education, maternal age, marital status and birth order.
      In particular, intellectual performance was not impaired among those with
      multiple compared with single defects. We conclude that for the majority of birth
      defect categories in the present birth cohort, our hypothesis that intellectual
      performance would be impaired was not confirmed. Thus, there seems to be little
      reason to fear an adverse intellectual outcome in non-disabled surviving infants
      with birth defects.

PMID- 16641212
TI  - Bone mineral density and bone metabolism in children treated for bone sarcomas.
AB  - In adolescent bone sarcoma patients, bone mass acquisition is potentially
      compromised at a time in which it should be at a maximum. To evaluate the problem
      we measured bone mineral density (BMD) and serum markers of bone formation and
      resorption in a series of pediatric patients with bone tumors. BMD was measured
      by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and
      the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean
      age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were:
      OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact
      PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We
      analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's
      sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was
      more pronounced in pubertal patients compared with those who had completed
      pubertal development at the time of disease diagnosis. Multivariate analysis
      indicated that sex, age, weight and BMI were significant in lumbar BMD depletion.
      Weight and BMI were significant in femoral BMD depletion. Serum markers of bone
      formation (PICP and OC) and resorption (ICTP) were, throughout, lower than
      reference values. Significant alterations in other markers were also observed. Up
      to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had
      some degree of BMD deficit. The corresponding increased risk of pathologic bone
      fractures constitutes a reduction in future quality of life.

PMID- 16641213
TI  - Does estrogen affect the development of abnormal vascular function in offspring
      of rats fed a low-protein diet in pregnancy?
AB  - It is established that there are gender-related differences in the effects on
      offspring blood pressure induced by maternal protein restriction in animal
      studies. Since such effects may depend on estrogen levels, we hypothesized that
      lower estrogen would induce an earlier onset of hypertension caused by maternal
      under-nutrition. Wistar rats were fed a diet containing either 18% (C) or 9% (R)
      casein throughout pregnancy. Half of the offspring in both C and R groups were
      ovariectomized on day 50 (CX, RX), and the other half underwent a sham operation
      (CO, RO). On d 175, offspring were killed for small artery reactivity and
      histologic investigation. Birth weight and later growth were not significantly
      different between C and R. RX had higher systolic blood pressure than CX on d125,
      but no difference was seen between RO and CO. On d 175, systolic blood pressure
      was higher in R than in C, whether or not ovariectomized. Dilator responses to
      acetylcholine and bradykinin in small mesenteric arteries were significantly
      attenuated in RX, although responses to SNP and isoprenaline showed no
      attenuation in R. The ratio of coronary peri-vascular fibrosis to total vascular
      area was higher in R, and the fibrosis became prominent in ovariectomized rats.
      These findings suggest that estrogen plays an important role in limiting the
      elevation of offspring blood pressure induced by maternal under-nutrition,
      possibly via BK-mediated mechanisms. The processes may underlie gender and life
      course patterns of hypertension and also the developmental origins of this
      disease.

PMID- 16641214
TI  - Surfactant protein D levels in umbilical cord blood and capillary blood of
      premature infants. The influence of perinatal factors.
AB  - Surfactant protein D (SP-D) is a collectin that plays an important role in the
      innate immune system and takes part in the surfactant homeostasis by regulating
      the surfactant pool size. The aims of this study were to investigate the values
      of SP-D in umbilical cord blood and capillary blood of premature infants and to
      relate the levels to perinatal conditions. A total of 254 premature infants were
      enrolled in the present study. Umbilical cord blood was drawn at the time of
      birth and capillary blood at regular intervals throughout the admission. The
      concentration of SP-D in umbilical cord blood and capillary blood was measured
      using ELISA technique. The median concentration of SP-D in umbilical cord blood
      was twice as high as in mature infants, 769 ng/mL (range 140-2,551), with lowest
      values in infants with intrauterine growth retardation (IUGR) and rupture of
      membranes (ROM). The median concentration of SP-D in capillary blood day 1 was
      1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM
      and delivered vaginally. High SP-D levels in umbilical cord blood and capillary
      blood on day 1 were found to be more likely in infants in need for respiratory
      support or surfactant treatment and susceptibility to infections. We conclude
      that SP-D concentrations in umbilical cord blood and capillary blood in premature
      infants are twice as high as in mature infants and depend on several perinatal
      conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1
      were found to be related to increased risk of RDS and infections.

PMID- 16641215
TI  - Bronchial muscle peristaltic activity in the fetal rat.
AB  - Aside for the potential for tonic contraction, the airway smooth muscle exhibits
      intermittent phasic rhythmic activity that may contribute to lung growth during
      fetal life. Therefore, we examined 4th generation rat 18-22 d gestation fetal, 4
      6 d of age newborn and adult bronchial ring from Sprague Dawley rats to compare
      differences in smooth muscle function. We hypothesized that phasic contractions
      were greatest before birth. Bronchial muscle spontaneous rhythmic contractions
      were greatest in the fetus and absent in the adult. In response to KCl
      stimulation, the fetal bronchial smooth muscle only developed tonic force that
      was 3.5 +/- 0.6 and lower than measured in the newborn 9.0 +/- 0.3 and adult 13.7
      +/- 1.4 mN/mm2. The thromboxane A2 analogue U46619 induced tonic and phasic
      muscle contractions and the amplitude and frequency of the phasic contractions
      were greater in the fetus as compared with the adult and increased with
      gestational age. The U46619-induced rhythmic contractions were abrogated by
      ryanodine, thapsigargin and reduction of extracellular Na+, suggesting
      intracellular Ca2+ dependence and involvement of the Na+/Ca2+ exchanger. The
      inward rectifier K+ blocker BaCl2 induced phasic contractions in unstimulated
      fetal, but not adult bronchial muscle of the same amplitude and frequency as for
      the spontaneous and U46619-induced ones. We conclude that the airway smooth
      muscle phasic activity is greatest in the fetus and tends to disappear post
      natally with age suggesting an in utero role during lung development.

PMID- 16641216
TI  - Dexamethasone suppresses expression of Nuclear Factor-kappaB in the cells of
      tracheobronchial lavage fluid in premature neonates with respiratory distress.
AB  - Nuclear Factor-kappaB (NF-kappaB) plays a central role in regulating the key
      mediators of inflammation involved in acute lung injury. The anti-inflammatory
      effect of steroids by suppressing pro-inflammatory cytokines may be mediated by
      inhibition of transcription factor NF-kappaB. The objective of this study was to
      determine the effect of glucocorticoid therapy on the expression of NF-kappaB in
      the cells of tracheobronchial lavage fluid (TBLF) in premature neonates with
      respiratory distress. Nineteen premature neonates requiring mechanical
      ventilation and receiving glucocorticoids were enrolled. Their gestational age
      (mean +/- SD) was 25.0 +/- 1.2 wk, birth weight 714 +/- 105 g and age of starting
      dexamethasone was 33 +/- 15 d. Tracheobronchial lavage fluid was collected before
      and 48-72 h after starting dexamethasone. NF-kappaB expression was measured by
      immunocytochemistry using mouse MAb against the p65 subunit of NF-kappaB on
      cytospin slides. The percent of cells stained and the intensity staining index
      were significantly higher before starting dexamethasone compared with after
      steroid therapy. Localization of NF-kappaB was significantly decreased in the
      cytoplasm and nuclei of mononuclear cells after initiation of dexamethasone
      therapy. The concentration of IL-8 was also significantly lower after starting
      dexamethasone. In conclusion, dexamethasone suppressed the expression of NF
      kappaB in the cytoplasm and nuclei of mononuclear cells and decreased levels of
      IL-8 in TBLF from premature neonates with respiratory distress. The anti
      inflammatory effects of corticosteroids may be mediated through NF-kappaB.

PMID- 16641217
TI  - Polymorphisms in the TNF-alpha promoter and variability in the granulomatous
      response in patients with Crohn's disease.
AB  - Granulomas may be found in 30-70% of patients with Crohn's disease (CD). The
      etiology of granuloma formation in CD is presently unknown. Elevated levels of
      TNF-alpha are found within granuloma tissue, and are required to maintain
      granuloma formation in animal models. TNF-alpha production has been shown to
      influenced by TNF-alpha promoter polymorphisms. We hypothesized that
      heterogeneity for granulomas in CD might be influenced by the TNF-alpha promoter
      genotype. Patients with confirmed CD that had undergone full colonoscopy with
      multiple biopsies and/or surgical resection, served as the study group. One
      hundred healthy individuals served as a control population for genotyping.
      Patients and controls underwent genotyping for four TNF-alpha polymorphisms:
      238G/A, 308 G/A,857 C/T, and 863 C/A. Inclusion and exclusion criteria were met
      in 155 patients (1-68 y). Polymorphisms in the TNF promoter were found in 16.6%
      (238G/A), 14.5% (308 G/A), 36.6% (857 C/T) and 30.7% (863G/A). No significant
      association was found for any of the individual polymorphisms with presence or
      absence of granulomas. In conclusion, we did not find an association between
      individual polymorphisms in the TNF-alpha promoter and presence of granulomas in
      CD. The reason for heterogeneity in granuloma formation in patients with CD
      remains elusive.

PMID- 16641218
TI  - Cimetidine does not prevent lung injury in newborn premature infants.
AB  - Animal studies have shown that induction of cytochrome P450 (CYP) in the lung by
      oxygen exposure may result in the release of free radical oxidants and
      arachidonic acid metabolites, which can cause lung injury that is reduced by
      treatment with cimetidine, a CYP inhibitor. To determine whether cimetidine would
      reduce lung injury in human infants at risk for chronic lung disease, we
      conducted a randomized clinical trial in which we administered either cimetidine
      or a placebo for 10 d beginning < 24 h after birth to 84 newborn infants weighing
      < or = 1250 g who were receiving O2 and mechanical ventilation. Cimetidine had no
      significant effect on severity of respiratory insufficiency assessed at 10 d
      postnatal age. F2-isoprostane levels (a marker of oxidant injury) in tracheal
      aspirates were significantly higher in the cimetidine group at 4 d and at 10 d.
      There were no significant differences between the groups in tracheal aspirate
      levels of inflammatory markers (leukotriene B4, IL-8, and nucleated cell count)
      or arachidonic acid metabolites. We conclude that cimetidine does not reduce lung
      injury in newborn premature infants receiving O2 and mechanical ventilation. It
      is possible that cimetidine was not an adequate CYP inhibitor in this context.

PMID- 16641219
TI  - Evaluation of arm anthropometry for assessing pediatric body composition:
      evidence from healthy and sick children.
AB  - Arm anthropometry is used as a proxy of body composition in clinical and field
      research but its validity has not been established in children. To address this
      issue, mid-upper arm circumference (MUAC) and triceps skinfold thickness (TS)
      were measured in 110 healthy children aged 4.4-13.9 y (55 boys) and 49 cystic
      fibrosis (CF) patients aged 8.1-13.4 y (22 boys). Reference values were arm and
      whole-body fat mass (FM) and fat-free mass (FFM) measured by dual x-ray
      absorptiometry and four-component model, respectively. Arm fat area (AFA), MUAC,
      and TS correlated well with arm FM (r = 0.84-0.92) and total FM (r = 0.78-0.92).
      Arm muscle area (AMA) and MUAC correlated well with arm FFM (r = 0.68-0.82) and
      total FFM (r = 0.60-0.86). After adjusting for age, sex, and height, arm
      anthropometry correlated strongly with FM but weakly with FFM. AFA, MUAC, and TS
      explained 67, 63, and 61% of variability in total FM in healthy children and 70,
      72, and 63% in CF. AMA and MUAC explained only 24 and 16% of variability in total
      FFM in healthy children and 33 and 28% in CF. Arm anthropometry is useful for
      predicting FM and ranking healthy children and patients for fatness. It has
      poorer success in predicting regional or total FFM.

PMID- 16641220
TI  - Natural history, outcome, and treatment efficacy in children and adults with
      glutaryl-CoA dehydrogenase deficiency.
AB  - Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare inborn disorder of L
      lysine, L-hydroxylysine, and L-tryptophan metabolism complicated by striatal
      damage during acute encephalopathic crises. Three decades after its description,
      the natural history and how to treat this disorder are still incompletely
      understood. To study which variables influenced the outcome, we conducted an
      international cross-sectional study in 35 metabolic centers. Our main outcome
      measures were onset and neurologic sequelae of acute encephalopathic crises. A
      total of 279 patients (160 male, 119 female) were included who were diagnosed
      clinically after clinical presentation (n = 218) or presymptomatically by
      neonatal screening (n = 23), high-risk screening (n = 24), or macrocephaly (n =
      14). Most symptomatic patients (n = 185) had encephalopathic crises,
      characteristically resulting in bilateral striatal damage and dystonia, secondary
      complications, and reduced life expectancy. First crises usually occurred during
      infancy (95% by age 2 y); the oldest age at which a repeat crisis was reported
      was 70 mo. In a few patients, neurologic disease developed without a reported
      crisis. Differences in the diagnostic criteria and therapeutic protocols for
      patients with GCDH deficiency resulted in a huge variability in the outcome
      worldwide. Recursive partitioning demonstrated that timely diagnosis in
      neurologically asymptomatic patients followed by treatment with L-carnitine and a
      lysine-restricted diet was the best predictor of good outcome, whereas treatment
      efficacy was low in patients diagnosed after the onset of neurologic disease.
      Notably, the biochemical phenotype did not predict the clinical phenotype. Our
      study proves GCDH deficiency to be a treatable disorder and a good candidate for
      neonatal screening.

PMID- 16641221
TI  - Mouse models for investigating the developmental basis of human birth defects.
AB  - Clinicians and basic scientists share an interest in discovering how genetic or
      environmental factors interact to perturb normal development and cause birth
      defects and human disease. Given the complexity of such interactions, it is not
      surprising that 4% of human infants are born with a congenital malformation, and
      cardiovascular defects occur in nearly 1%. Our research is based on the
      fundamental hypothesis that an understanding of normal and abnormal development
      will permit us to generate effective strategies for both prevention and treatment
      of human birth defects. Animal models are invaluable in these efforts because
      they allow one to interrogate the genetic, molecular and cellular events that
      distinguish normal from abnormal development. Several features of the mouse make
      it a particularly powerful experimental model: it is a mammalian system with
      similar embryology, anatomy and physiology to humans; genes, proteins and
      regulatory programs are largely conserved between human and mouse; and finally,
      gene targeting in murine embryonic stem cells has made the mouse genome amenable
      to sophisticated genetic manipulation currently unavailable in any other model
      organism.

PMID- 16641222
TI  - Believe in your placebo.

PMID- 16641223
TI  - In vivo magnetic resonance imaging and semiautomated image analysis extend the
      brain phenotype for cdf/cdf mice.
AB  - Magnetic resonance imaging and computer image analysis in human clinical studies
      effectively identify abnormal neuroanatomy in disease populations. As more mouse
      models of neurological disorders are discovered, such an approach may prove
      useful for translational studies. Here, we demonstrate the effectiveness of a
      similar strategy for mouse neuroscience studies by phenotyping mice with the
      cerebellar deficient folia (cdf) mutation. Using in vivo multiple-mouse magnetic
      resonance imaging for increased throughput, we imaged groups of cdf mutant,
      heterozygous, and wild-type mice and made an atlas-based segmentation of the
      structures in 15 individual brains. We then performed computer automated volume
      measurements on the structures. We found a reduced cerebellar volume in the cdf
      mutants, which was expected, but we also found a new phenotype in the inferior
      colliculus and the olfactory bulbs. Subsequent local histology revealed
      additional cytoarchitectural abnormalities in the olfactory bulbs. This
      demonstrates the utility of anatomical magnetic resonance imaging and
      semiautomated image analysis for detecting abnormal neuroarchitecture in mutant
      mice.

PMID- 16641224
TI  - Radial migration of superficial layer cortical neurons controlled by novel Ig
      cell adhesion molecule MDGA1.
AB  - MAM (meprin/A5 protein/receptor protein tyrosine phosphatase mu) domain
      glycosylphosphatidylinositol anchor 1 (MDGA1), a unique cell surface
      glycoprotein, is similar to Ig-containing cell adhesion molecules that influence
      neuronal migration and process outgrowth. We show in postnatal mice that MDGA1 is
      expressed by layer 2/3 neurons throughout the neocortex. During development,
      MDGA1 is expressed in patterns consistent with its expression by migrating layer
      2/3 neurons, suggesting a role for MDGA1 in controlling their migration and
      settling in the superficial cortical plate. To test this hypothesis, we performed
      loss-of-function studies using RNA interference (RNAi) targeting different
      sequences of mouse MDGA1. RNAi or empty vectors were coelectroporated with an
      enhanced green fluorescent protein reporter in utero into the lateral ventricle
      at embryonic day 15.5 to transfect progenitors of superficial layer neurons; the
      distributions of transfected neurons were analyzed late on postnatal day 0. We
      found a direct correlation between effectiveness of an RNAi in suppressing MDGA1
      expression and disrupting migration of superficial layer neurons. An RNAi with no
      effect on MDGA1 expression has no effect on the migration. In contrast, an RNAi
      that suppresses MDGA1 expression also blocks proper migration of transfected
      superficial layer neurons, with essentially all transfected cells found deep in
      the cortical plate or beneath it. This migration defect is rescued by
      cotransfection of a rat MDGA1 expression construct along with the effective RNAi,
      confirming that the RNAi effect is specific to diminishing mouse MDGA1
      expression. RNAi transfections of deep layer neurons that do not express MDGA1 do
      not significantly affect their migration. We conclude that MDGA1 acts cell
      autonomously to control the migration of MDGA1-expressing superficial layer
      cortical neurons.

PMID- 16641225
TI  - Content- and task-specific dissociations of frontal activity during maintenance
      and manipulation in visual working memory.
AB  - Working memory, the short-term maintenance and manipulation of information,
      relies strongly on neural activity in the frontal cortex. Understanding the
      functional role of this activity is a prerequisite for the understanding of
      cognitive control mechanisms. Functional imaging studies in human participants
      have attempted to reveal neural correlates of the subdivision of visual working
      memory into different processes (maintenance vs manipulation) and according to
      the type of memorized content. Here, we show, using functional magnetic resonance
      imaging, a content-specific dissociation of frontal activity, with dorsal
      premotor areas supporting both maintenance and manipulation of spatial features
      and more ventral areas supporting maintenance and manipulation of color.
      Manipulation-specific activity was observed in the anterior middle frontal gyrus,
      the inferior frontal junction, and the inferior parietal lobe bilaterally. These
      areas have been implicated in cognitive control, and their activation by the
      manipulation task conforms to the demand on central executive resources in this
      condition. We suggest that the enhanced demand on cognitive resources in
      manipulation compared with maintenance was met by interplay of content- and task
      specific modules in a frontoparietal network.

PMID- 16641226
TI  - GAP-independent termination of photoreceptor light response by excess gamma
      subunit of the cGMP-phosphodiesterase.
AB  - We have generated a mouse with rod photoreceptors overexpressing the gamma
      inhibitory subunit (PDE6gamma) of the photoreceptor G-protein effector cGMP
      phosphodiesterase (PDE6). PDE6gamma overexpression decreases the rate of rise of
      the rod response at dim intensities, indicating a reduction in the gain of
      transduction that may be the result of cytoplasmic PDE6gamma binding to activated
      transducin alpha GTP (Talpha-GTP) before the Talpha-GTP binds to endogenous
      PDE6gamma. Excess PDE6gamma also produces a marked acceleration in the falling
      phase of the light response and more rapid recovery of sensitivity and
      circulating current after prolonged light exposure. These effects are not
      mediated by accelerating GTP hydrolysis through the GAP (GTPase activating
      protein) complex, because the decay of the light response is also accelerated in
      rods that overexpress PDE6gamma but lack RGS9. Our results show that the
      PDE6gamma binding sites of PDE6 alpha and beta are accessible to excess
      (presumably cytoplasmic) PDE6gamma in the light, once endogenous PDE6gamma has
      been displaced from its binding site by Talpha-GTP. They also suggest that in the
      presence of Talpha-GTP, the PDE6gamma remains attached to the rest of the PDE6
      molecule, but after conversion of Talpha-GTP to Talpha-GDP, the PDE6gamma may
      dissociate from the PDE6 and exchange with a cytoplasmic pool. This pool may
      exist even in wild-type rods and may explain the decay of rod photoresponses in
      the presence of nonhydrolyzable analogs of GTP.

PMID- 16641227
TI  - Basic fibroblast growth factor protects against rotenone-induced dopaminergic
      cell death through activation of extracellular signal-regulated kinases 1/2 and
      phosphatidylinositol-3 kinase pathways.
AB  - Administration of rotenone to rats reproduces many features of Parkinson's
      disease, including dopaminergic neuron degeneration, and provides a useful model
      to study the pathogenesis of Parkinson's disease. However, the cell death
      mechanisms induced by rotenone and potential neuroprotective mechanisms against
      rotenone are not well defined. Here we report that rotenone-induced apoptosis in
      human dopaminergic SH-SY5Y cells is attenuated by pretreatment with several
      growth factors, most notably basic fibroblast growth factor (bFGF). bFGF
      activated both extracellular signal-regulated kinase 1/2 (ERK1/2) and
      phosphatidylinositol-3 kinase (PI3-kinase) pathways in SH-SY5Y cells. Ectopic
      activation of ERK1/2 or PI3-kinase protected against rotenone, whereas inhibition
      of either pathway attenuated bFGF protection. Reducing the expression of the
      proapoptotic protein Bcl-2-associated death protein (BAD) by small interfering
      RNA rendered SH-SY5Y cells resistant to rotenone, implicating BAD in rotenone
      induced cell death. Interestingly, bFGF induced a long-lasting phosphorylation of
      BAD at serine 112, suggesting BAD inactivation through the ERK1/2 signaling
      pathway. Moreover, primary cultured dopaminergic neurons from mesencephalon were
      more sensitive to rotenone-induced cell death than nondopaminergic neurons in the
      same culture. The loss of dopaminergic neurons was blocked by bFGF, an inhibition
      dependent on ERK1/2 and PI3-kinase signaling. These data suggest that rotenone
      induced dopaminergic cell death requires BAD and identify bFGF and its activation
      of ERK1/2 and PI3-kinase signaling pathways as novel intervention strategies to
      block cell death in the rotenone model of Parkinson's disease.

PMID- 16641228
TI  - State-dependent cross-linking of the M2 and M3 segments: functional basis for the
      alignment of GABAA and acetylcholine receptor M3 segments.
AB  - Construction of a GABAA receptor homology model based on the acetylcholine (ACh)
      receptor structure is complicated by the low sequence similarity between GABAA
      and ACh M3 transmembrane segments that creates significant uncertainty in their
      alignment. We determined the orientation of the GABAA M2 and M3 transmembrane
      segments using disulfide cross-linking. The M2 residues alpha1M266 (11') and
      alpha1T267 (12') were mutated to cysteine in either wild type or single M3
      cysteine mutant (alpha1V297C, alpha1A300C to alpha1A305C) backgrounds. We assayed
      spontaneous and induced disulfide bond formation. Reduction with DTT
      significantly potentiated GABA-induced currents in alpha1T267C-L301C and
      alpha1T267C-F304C. Copper phenanthroline-induced oxidation inhibited GABA-induced
      currents in these mutants and in alpha1T267C-A305C. Intrasubunit disulfide bonds
      formed between these Cys pairs, implying that the alpha-carbon separation was at
      most 5.6 A. The reactive alpha1M3 residues (L301, F304, A305) lie on the same
      face of an alpha-helix. The unresponsive ones (A300, I302, E303) lie on the
      opposite face. In the resting state, the reactive side of alpha1M3 faces M2
      alpha1T267. In conjunction with the ACh structure, our data indicate that
      alignment of GABAA and ACh M3 requires a single gap in the GABAA M2-M3 loop. In
      the presence of GABA, oxidation of alpha1T267C-L301C and alpha1T267C-F304C had no
      effect, but oxidation of alpha1T267C-A305C caused a significant increase in
      spontaneous channel opening. We infer that, as the channel opens, the distance
      and/or orientation between M2-alpha1T267 and M3-alpha1A305 changes such that the
      disulfide bond stabilizes the open state. This begins to define the
      conformational motion that M2 undergoes during channel opening.

PMID- 16641229
TI  - Neuroprotection by transgenic expression of glucose-6-phosphate dehydrogenase in
      dopaminergic nigrostriatal neurons of mice.
AB  - Oxidative damage to dopaminergic nigrostriatal (DNS) neurons plays a central role
      in the pathogenesis of Parkinson's disease (PD). Glucose-6-phosphate
      dehydrogenase (G6PD) is a key cytoprotective enzyme that provides NADPH, the
      major source of the reducing equivalents of a cell. Mutations of this enzyme are
      the most common enzymopathies worldwide. We have studied in vivo the role of G6PD
      overexpressed specifically in the DNS pathway and show that the increase of G6PD
      activity in the soma and axon terminals of DNS neurons, separately from other
      neurons or glial cells, protects them from parkinsonism. Analysis of DNS neurons
      by histological, neurochemical, and functional methods showed that even a
      moderate increase of G6PD activity rendered transgenic mice more resistant than
      control littermates to the toxic effects of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The neuroprotective action of G6PD was also observed
      in aged animals despite that they had a greater susceptibility to MPTP.
      Therefore, overexpression of G6PD in dopaminergic neurons or pharmacological
      activation of the native enzyme should be considered as potential therapeutic
      strategies to PD.

PMID- 16641230
TI  - Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal
      excitability.
AB  - Neuroprotection can be induced by low doses of NMDA, which activate both synaptic
      and extrasynaptic NMDA receptors. This is in apparent contradiction with our
      recent findings that extrasynaptic NMDA receptor signaling exerts a dominant
      inhibitory effect on prosurvival signaling from synaptic NMDA receptors. Here we
      report that exposure to low preconditioning doses of NMDA results in preferential
      activation of synaptic NMDA receptors because of a dramatic increase in action
      potential firing. Both acute and long-lasting phases of neuroprotection in the
      face of apoptotic or excitotoxic insults are dependent on this firing
      enhancement. Key mediators of synaptic NMDA receptor-dependent neuroprotection,
      phosphatidylinositol 3 kinase-Akt (PI3 kinase-Akt) signaling to Forkhead box
      subgroup O (FOXO) export and glycogen synthase kinase 3beta (GSK3beta) inhibition
      and cAMP response element-binding protein-dependent (CREB-dependent) activation
      of brain-derived neurotrophic factor (BDNF), can be induced only by low doses of
      NMDA via this action potential-dependent route. In contrast, NMDA doses on the
      other side of the toxicity threshold do not favor synaptic NMDA receptor
      activation because they strongly suppress firing rates below baseline. The
      classic bell-shaped curve depicting neuronal fate in response to NMDA dose can be
      viewed as the net effect of two antagonizing (synaptic vs extrasynaptic) curves:
      via increased firing the synaptic signaling dominates at low doses, whereas
      firing becomes suppressed and extrasynaptic signaling dominates as the toxicity
      threshold is crossed.

PMID- 16641231
TI  - Anticipatory movement timing using prediction and external cues.
AB  - Animals often make anticipatory movements to compensate for slow reaction times.
      Anticipatory movements can be timed using external, sensory cues, or by an
      internal prediction of when an event will occur. However, it is unknown whether
      external or internal cues dominate the anticipatory response when both are
      present. Smooth pursuit eye movements are generated by a motor system heavily
      influenced by anticipation. We measured pursuit to determine how its timing was
      influenced when both a predictable event and a visual cue were present. Monkeys
      tracked a moving target that appeared at a constant time relative to the onset of
      a fixation point. At a randomized time before target onset, the fixation point
      disappeared, creating a temporal "gap" that cued impending target motion. We
      found that the gap onset cue and prediction of target onset together determined
      pursuit initiation time. We also investigated whether prediction could override
      the gap onset cue or vice versa by manipulating target onset and, hence, the
      duration of time that the animal had to estimate to predict it. When target
      motion began earlier, the pursuit system relied more on prediction to trigger a
      movement, whereas the cue was more often used when the target moved later.
      Pursuit latency in previous trials partially accounted for this behavior. The
      results suggest that neither internal nor external factors dominate to control
      the anticipatory response and that the relative contributions vary with stimulus
      conditions. A model in which neuronal anticipation and fixation signals interact
      can explain the results.

PMID- 16641232
TI  - Transport of information along unidimensional layered networks of dissociated
      hippocampal neurons and implications for rate coding.
AB  - The ability of synchronous population activity in layered networks to transmit a
      rate code is a focus of recent debate. We investigate these issues using a
      patterned unidimensional hippocampal culture. The network exhibits population
      bursts that travel its full length, with the advantage that signals propagate
      along a clearly defined path. The amplitudes of activity are measured using
      calcium imaging, a good approximate of population rate code, and the distortion
      of the signal as it travels is analyzed. We demonstrate that propagation along
      the line is precisely described by information theory as a chain of Gaussian
      communication channels. The balance of excitatory and inhibitory synapses is
      crucial for this transmission. However, amplitude information carried along this
      layered neuronal structure fails within 3 mm, approximately 10 mean axon lengths,
      and is limited by noise in the synaptic transmission. We conclude that rate codes
      cannot be reliably transmitted through long layered networks.

PMID- 16641233
TI  - Neocortical network activity in vivo is generated through a dynamic balance of
      excitation and inhibition.
AB  - The recurrent excitatory and inhibitory connections between and within layers of
      the cerebral cortex are fundamental to the operation of local cortical circuits.
      Models of cortical function often assume that recurrent excitation and inhibition
      are balanced, and we recently demonstrated that spontaneous network activity in
      vitro contains a precise balance of excitation and inhibition; however, the
      existence of a balance between excitation and inhibition in the intact and
      spontaneously active cerebral cortex has not been directly tested. We examined
      this hypothesis in the prefrontal cortex in vivo, during the slow (<1 Hz)
      oscillation in ketamine-xylazine-anesthetized ferrets. We measured persistent
      network activity (Up states) with extracellular multiple unit and local field
      potential recording, while simultaneously recording synaptic currents in nearby
      cells. We determined the reversal potential and conductance change over time
      during Up states and found that the body of Up state activity exhibited a steady
      reversal potential (-37 mV on average) for hundreds of milliseconds, even during
      substantial (21 nS on average) changes in membrane conductance. Furthermore, we
      found that both the initial and final segments of the Up state were characterized
      by significantly more depolarized reversal potentials and concomitant increases
      in excitatory conductance, compared with the stable middle portions of Up states.
      This ongoing temporal evolution between excitation and inhibition, which exhibits
      remarkable proportionality within and across neurons in active local networks,
      may allow for rapid transitions between relatively stable network states,
      permitting the modulation of neuronal responsiveness in a behaviorally relevant
      manner.

PMID- 16641234
TI  - Hippocampal lesion prevents spatial relational learning in adult macaque monkeys.
AB  - The role of the hippocampus in spatial learning and memory has been extensively
      studied in rodents. Comparable studies in nonhuman primates, however, are few,
      and findings are often contradictory. This may be attributable to the failure to
      distinguish between allocentric and egocentric spatial representations in
      experimental designs. For this experiment, six adult monkeys received bilateral
      hippocampal ibotenic acid lesions, and six control subjects underwent sham
      surgery. Freely moving monkeys then foraged for food located in two arrays of
      three distinct locations among 18 locations distributed in an open-field arena.
      Multiple goals and four pseudorandomly chosen entrance points precluded the
      monkeys' ability to rely on an egocentric strategy to identify food locations.
      Monkeys were tested in two conditions. First, local visual cues marked the food
      locations. Second, no local cues marked the food locations, so that monkeys had
      to rely on an allocentric (spatial relational) representation of the environment
      to discriminate these locations. Both hippocampal-lesioned and control monkeys
      discriminated the food locations in the presence of local cues. However, in the
      absence of local cues, control subjects discriminated the food locations, whereas
      hippocampal-lesioned monkeys were unable to do so. Interestingly, histological
      analysis of the brain of one control monkey whose behavior was identical to that
      of the experimentally lesioned animals revealed a bilateral ischemic lesion
      restricted to the hippocampus. These findings demonstrate that the adult monkey
      hippocampal formation is critical for the establishment or use of allocentric
      spatial representations and that selective damage of the hippocampus prevents
      spatial relational learning in adult nonhuman primates.

PMID- 16641235
TI  - Characterization of a soluble ligand binding domain of the NMDA receptor
      regulatory subunit NR3A.
AB  - NR3A is expressed widely in the developing CNS of mammals. Coassembly of NR3A
      with NR1 and NR2 modifies NMDA receptor-mediated responses, reducing calcium
      permeability and single-channel conductance. The ligand binding properties of
      NR3A are unknown but shape the role NR3A plays when incorporated into NMDA
      receptors. Here, a soluble NR3A ligand binding domain (NR3A S1S2) was constructed
      based on amino acid sequence alignments with other glutamate receptor ion
      channels and is expressed in Escherichia coli. After purification by affinity,
      gel filtration, and ion exchange chromatography, NR3A S1S2 behaves as a monomer
      even at a concentration of 20 mg/ml, as determined by size-exclusion
      chromatography and dynamic light scattering. NR3A S1S2 has very high affinity for
      glycine with an apparent dissociation constant (Kd) of 40 nm, 650-fold less than
      the Kd for NR1. Glutamate, which binds to NR2 subunits, also binds to NR3A, but
      with very low affinity (Kd = 9.6 mm); in contrast, binding of glutamate to NR1
      was not detectable even at a 300 mm concentration. The antagonist binding
      profiles of NR3A and NR1 also show striking differences. 6-cyano-2,3-dihydroxy-7
      nitro-quinoxaline (CNQX), and its analog CGP78608, bind to NR3A S1S2 with low
      micromolar affinity, whereas for NR1, the affinity of CGP78608 increases 1000
      fold compared with CNQX. Other high-affinity NR1 antagonists also show very weak
      binding to NR3A. Proteolysis protection experiments reveal that CNQX and CGP78608
      bind to and stabilize domain 1 of NR3A S1S2 but increase proteolysis of domain 2,
      indicating that they produce conformational changes distinct from those induced
      by glycine and D-serine.

PMID- 16641236
TI  - The dopamine D2 receptor regulates the development of dopaminergic neurons via
      extracellular signal-regulated kinase and Nurr1 activation.
AB  - Because the dopaminergic pathways in the midbrain have been closely associated
      with serious neuropsychiatric disorders, the elucidation of the mechanisms
      underlying dopaminergic neuronal development should provide some important clues
      for related disorders. In mice lacking the dopamine D2 receptor (D2R-/-),
      stereological cell counting analysis showed that the number of mesencephalic
      tyrosine hydroxylase (TH) cells was significantly low during ontogeny, compared
      with that observed in wild-type (WT) mice, thereby indicating an alteration in
      dopaminergic neuronal development in the absence of D2R. The results of
      immunohistochemical and reverse transcription-PCR analyses revealed that the
      expression of Nurr1, an orphan nuclear receptor, as well as Ptx3 expression, was
      selectively reduced in D2R-/- mice during the embryonic stage. A reporter gene
      assay using the Nur response element linked to the luciferase reporter gene
      indicated that the stimulation of D2R results in the activation of the Nurr1
      mediated reporter gene. This D2R-mediated Nur response element-dependent
      transcriptional activity was regulated via the activation of extracellular signal
      regulated kinase (ERK). Furthermore, quinpirole treatment was shown to elicit an
      increase in the number of TH-positive neurons, as well as the neuritic extension
      of TH neurons, coupled with ERK activation and Nurr1 activation in the TH
      positive neurons in primary mesencephalic cultures from WT mice. However, this
      regulation was not detected in the D2R-/- mice. These results suggest that
      signaling through D2R in association with Nurr1 using ERK, plays a critical role
      in mesencephalic dopaminergic neuronal development.

PMID- 16641237
TI  - Host response and dysfunction in the CNS during chronic simian immunodeficiency
      virus infection.
AB  - CNS abnormalities can be detected during chronic human immunodeficiency virus
      (HIV) infection, before the development of opportunistic infections or other
      sequelae of immunodeficiency. However, although end-stage dementia caused by HIV
      has been linked to the presence of infected and activated macrophages and
      microglia in the brain, the nature of the changes resulting in the motor and
      cognitive disorders in the chronic stage is unknown. Using simian
      immunodeficiency virus-infected rhesus monkeys, we sought the molecular basis for
      CNS dysfunction. In the chronic stable stage, nearly 2 years after infection, all
      animals had verified CNS functional abnormalities. Both virus and infiltrating
      lymphocytes (CD8+ T-cells) were found in the brain. Molecular analysis revealed
      that the expression of several immune response genes was increased, including
      CCL5, which has pleiotropic effects on neurons as well as immune cells. CCL5 was
      significantly upregulated throughout the course of infection, and in the chronic
      phase was present in the infiltrating lymphocytes. We have identified an altered
      state of the CNS at an important stage of the viral-host interaction, likely
      arising to protect against the virus but in the long term leading to damaging
      processes.

PMID- 16641238
TI  - Activity-dependent movements of postsynaptic scaffolds at inhibitory synapses.
AB  - Dendritic spines show an activity-dependent cytoskeleton-based remodeling coupled
      with variations in receptor number and the functional properties of excitatory
      synapses. In this study, we analyzed the dynamics of gephyrin containing
      inhibitory postsynaptic scaffolds imaging a Venus::gephyrin (VeGe) chimera in
      dissociated spinal cord neurons. We provide evidence that the postsynaptic
      scaffolds at mature synapses display a submicrometric rapid lateral motion and
      are continuously moving on the dendritic shaft. This dynamic behavior is calcium
      dependent and is controlled by the cytoskeleton. Minute rearrangement within the
      gephyrin scaffold as well as the scaffold lateral displacements are F-actin
      dependent. The lateral movements are counteracted by microtubules. Moreover, the
      action of the potassium channel blocker 4-aminopyridine and receptor antagonists
      indicate that the dynamics of postsynaptic gephyrin scaffolds are controlled by
      synaptic activity.

PMID- 16641239
TI  - Working memory for conjunctions relies on the medial temporal lobe.
AB  - A prominent theory of hippocampal function proposes that the hippocampus is
      importantly involved in relating or binding together separate pieces of
      information to form an episodic representation. This hypothesis has only been
      applied to studies of long-term memory because the paradigmatic view of the
      hippocampus is that it is not critical for short-term forms of memory. However,
      relational processing is important in many working memory tasks, especially tasks
      using visual stimuli. Here, we test the hypothesis that the medial temporal lobes
      are important for relational memory even over short delays. The task required
      patients with medial temporal lobe amnesia and controls to remember three
      objects, locations, or object-location conjunctions over 1 or 8 s delays. The
      results show that working memory for objects and locations was at normal levels,
      but that memory for conjunctions was severely impaired at 8 s delays. Additional
      analyses suggest that the hippocampus per se is critical for accurate conjunction
      working memory. We propose that the hippocampus is critically involved in memory
      for conjunctions at both short and long delays.

PMID- 16641240
TI  - Interaction of Kv3 potassium channels and resurgent sodium current influences the
      rate of spontaneous firing of Purkinje neurons.
AB  - Purkinje neurons spontaneously generate action potentials in the absence of
      synaptic drive and thereby exert a tonic, yet plastic, input to their target
      cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents
      with biophysical properties that are specialized for high-frequency firing:
      resurgent sodium currents and potassium currents mediated by Kv3.3. How these
      ionic currents determine the intrinsic activity of Purkinje neurons has only
      partially been understood. Purkinje neurons from mutant mice lacking Kv3.3 have a
      reduced rate of spontaneous firing. Dynamic-clamp recordings demonstrated that
      normal firing rates are rescued by inserting artificial Kv3 currents into Kv3.3
      knock-out Purkinje neurons. Numerical simulations indicated that Kv3.3 increases
      the spontaneous firing rate via cooperation with resurgent sodium currents. We
      conclude that the rate of spontaneous action potential firing of Purkinje neurons
      is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium
      currents.

PMID- 16641241
TI  - Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal
      cortex in a model of temporal lobe epilepsy.
AB  - Temporal lobe epilepsy is the most common type of epilepsy in adults, and its
      pathophysiology remains unclear. Layer II stellate cells of the entorhinal
      cortex, which are hyperexcitable in animal models of temporal lobe epilepsy,
      provide the predominant synaptic input to the hippocampal dentate gyrus. Previous
      studies have ascribed the hyperexcitability of layer II stellate cells to
      GABAergic interneurons becoming "dormant" after disconnection from their
      excitatory synaptic inputs, which has been reported to occur during preferential
      loss of layer III pyramidal cells. We used whole-cell recording from slices of
      entorhinal cortex in pilocarpine-treated epileptic rats to test the dormant
      interneuron hypothesis. Hyperexcitability appeared as multiple action potentials
      and prolonged depolarizations evoked in layer II stellate cells of epileptic rats
      but not controls. However, blockade of glutamatergic synaptic transmission caused
      similar percentage reductions in the frequency of spontaneous IPSCs in layer II
      stellate cells of control and epileptic rats, suggesting similar levels of
      excitatory synaptic input to GABAergic interneurons. Direct recordings and
      biocytin labeling revealed two major types of interneurons in layer III whose
      excitatory synaptic drive in epileptic animals was undiminished. Interneurons in
      layer III did not appear to be dormant; therefore, we tested whether loss of
      GABAergic synapses might underlie hyperexcitability of layer II stellate cells.
      Stereological evidence of fewer GABAergic interneurons, fewer gephyrin
      immunoreactive punctae, and reduced frequency of spontaneous IPSCs and miniature
      IPSCs (recorded in tetrodotoxin) confirmed that layer II stellate cell
      hyperexcitability is attributable, at least in part, to reduced inhibitory
      synaptic input.

PMID- 16641242
TI  - Role of cAMP response element-binding protein in the rat locus ceruleus:
      regulation of neuronal activity and opiate withdrawal behaviors.
AB  - The transcription factor cAMP response element-binding protein (CREB) is
      implicated in mediating the actions of chronic morphine in the locus ceruleus
      (LC), but direct evidence to support such a role is limited. Here, we
      investigated the influence of CREB on LC neuronal activity and opiate withdrawal
      behaviors by selectively manipulating CREB activity in the LC using viral vectors
      encoding genes for CREBGFP (wild-type CREB tagged with green fluorescent
      protein), caCREBGFP (a constitutively active CREB mutant), dnCREBGFP (a dominant
      negative CREB mutant), or GFP alone as a control. Our results show that in vivo
      overexpression of CREBGFP in the LC significantly aggravated particular morphine
      withdrawal behaviors, whereas dnCREBGFP expression attenuated these behaviors. At
      the cellular level, CREBGFP expression in the LC in vivo and in vitro had no
      significant effect on neuronal firing at baseline but enhanced the excitatory
      effect of forskolin (an activator of adenylyl cyclase) on these neurons, which
      suggests that the cAMP signaling pathway in these neurons was sensitized after
      CREB expression. Moreover, in vitro studies showed that caCREBGFP-expressing LC
      neurons fired significantly faster and had a more depolarized resting membrane
      potential compared with GFP-expressing control cells. Conversely, LC neuronal
      activity was decreased by dnCREBGFP, and the neurons were hyperpolarized by this
      treatment. Together, these data provide direct evidence that CREB plays an
      important role in controlling the electrical excitability of LC neurons and that
      morphine-induced increases in CREB activity contribute to the behavioral and
      neural adaptations associated with opiate dependence and withdrawal.

PMID- 16641243
TI  - A role for synaptotagmin VII-regulated exocytosis of lysosomes in neurite
      outgrowth from primary sympathetic neurons.
AB  - Neurite outgrowth is mediated by the exocytosis of intracellular vesicles at the
      tips of elongating neuronal processes. The lysosomal vesicle-associated soluble N
      ethylmaleimide-sensitive factor attachment protein receptor tetanus neurotoxin
      insensitive vesicle-associated membrane protein (TI-VAMP)/VAMP7 was previously
      implicated in membrane fusion events mediating neurite outgrowth, but the
      participation of lysosomes in this exocytic process has remained unclear. Here,
      we show that VAMP7 and the lysosomal glycoprotein Lamp1 extensively colocalize in
      vesicles present throughout the soma and neurite outgrowths of primary
      sympathetic neurons. Synaptotagmin VII (Syt VII), a Ca(2+)-sensing synaptotagmin
      isoform previously shown to interact with VAMP7 during lysosomal exocytosis in
      fibroblasts, was detected on a subset of these lysosomal glycoprotein 1
      (Lamp1)/VAMP7-positive neuronal vesicles. Ionophore-stimulated exocytosis
      triggered exposure of the luminal domains of both Lamp1 and Syt VII at
      overlapping sites on the neuronal surface, indicating that the Syt VII-containing
      lysosomal compartments fuse with the plasma membrane in response to [Ca2+]i
      elevation. To determine whether Syt VII was required for the exocytic events
      mediating neurite extension, we followed the development of superior cervical
      ganglion neurons explanted from Syt VII-deficient mice. The results revealed a
      marked defect in neurite outgrowth and arborization, suggesting that Ca(2+)
      dependent, Syt VII-regulated exocytosis of late endosomes/lysosomes plays a role
      in the addition of new membrane to developing neurite extensions.

PMID- 16641244
TI  - Effects of early life stress on [11C]DASB positron emission tomography imaging of
      serotonin transporters in adolescent peer- and mother-reared rhesus monkeys.
AB  - Peer-reared (PR) rhesus monkeys with early maternal separation later exhibit
      aggressiveness, impaired impulse control, alcohol abuse, and low CSF 5
      hydroxyindoleacetic acid. This study compared regional brain serotonin
      transporter (SERT) binding between nine PR and seven mother-reared rhesus monkeys
      with [11C]DASB positron emission tomography (PET) imaging. Parametric images of
      binding potential (BP) (which is proportional to Bmax/KD, in which Bmax is
      transporter density and KD is dissociation constant) and relative blood flow (R1)
      were generated by the two-parameter multilinear reference tissue model. R1 images
      were used for coregistration and normalization of PET parametric data to the
      magnetic resonance imaging template space. Group BP differences were analyzed
      voxelwise by Student's t test in SPM2. Region of interest-based parameter values
      were also calculated to obtain the magnitude of regional BP differences between
      the two groups. For the PR group, SERT BP was decreased by 10-23% across a range
      of brain areas consisting of the raphe, thalamus, hypothalamus, caudate and
      putamen, globus pallidum, anterior cingulate gyrus, and medial temporal regions,
      including amygdala and hippocampus (cluster-level corrected p = 0.002). For the
      latter three regions, BP was decreased in the right hemisphere. These results
      agree with the hypothesis that early maternal deprivation affects the development
      of the serotonergic system and suggest that decreased serotonergic innervations
      in the critical brain regions may explain some of the behavioral and biochemical
      abnormalities in PR monkeys.

PMID- 16641245
TI  - Beta-amyloid stimulates murine postnatal and adult microglia cultures in a unique
      manner.
AB  - Reactive microglia are commonly observed in association with the beta-amyloid
      (Abeta) plaques of Alzheimer's disease brains. This localization supports the
      hypothesis that Abeta is a specific activating stimulus for microglia. A variety
      of in vitro studies have used postnatal derived rodent microglia cultures to
      characterize the ability of Abeta to stimulate these cells. However, it is
      unclear whether this paradigm accurately models conditions in aged animals. To
      determine whether Abeta stimulatory phenotypes differ between young and adult
      microglia, we established cultures of acutely isolated adult murine cortical
      microglia to compare with postnatal derived microglial cultures. Although cells
      from both ages expressed robust immunoreactivity for CD68 and CD11b, their
      responses to activating stimuli differed. Fibrillar Abeta was rapidly
      phagocytosed by postnatal microglia and both oligomeric and fibrillar peptide
      stimulated increased tumor necrosis factor alpha (TNFalpha) secretion. However,
      Abeta oligomers but not fibrils stimulated TNFalpha secretion from adult
      microglia. More importantly, adult microglia had diminished ability to
      phagocytose Abeta fibrils. These findings demonstrate that adult microglia
      respond to Abeta fibril stimulation uniquely from postnatal cells and suggest
      that adult rather than postnatal microglia cultures are more appropriate for
      modeling proinflammatory changes in the aged CNS.

PMID- 16641246
TI  - CA150 expression delays striatal cell death in overexpression and knock-in
      conditions for mutant huntingtin neurotoxicity.
AB  - Transcriptional dysregulation caused by expanded polyglutamines (polyGlns) in
      huntingtin (htt) may be central to cell-autonomous mechanisms for neuronal cell
      death in Huntington's disease (HD) pathogenesis. We hypothesized that these
      mechanisms may involve the dysfunction of the transcriptional regulator CA150, a
      putative modifier of onset age in HD, because it binds to htt and accumulates in
      an HD grade-dependent manner in striatal and cortical neurons. Consistently, we
      report herein that CA150 expression rescues striatal cell death in lentiviral
      overexpression (rats) and knock-in (mouse cells) conditions for mutant htt
      neurotoxicity. In both systems, rescue was dependent on the (Gln-Ala)38 repeat
      normally found in CA150. We excluded the possibility that rescue may be caused by
      the (Gln-Ala)38 repeat interacting with polyGlns and, by doing so, blocking
      mutant htt toxicity. In contrast, we found the (Gln-Ala)38 repeat is required for
      the nuclear restriction of exogenous CA150, suggesting that rescue requires
      nuclear CA150. Additionally, we found the (Gln-Ala)38 repeat was dispensable for
      CA150 transcriptional repression ability, suggesting further that CA150
      localization is critical to rescue. Finally, rescue was associated with increased
      neuritic aggregation, with no reduction of nuclear inclusions, suggesting the
      solubilization and nuclear export of mutant htt. Together, our data indicate that
      mutant htt may induce CA150 dysfunction in striatal neurons and suggest that the
      restoration of nuclear protein cooperativity may be neuroprotective.

PMID- 16641247
TI  - Mice lacking brain/kidney phosphate-activated glutaminase have impaired
      glutamatergic synaptic transmission, altered breathing, disorganized goal
      directed behavior and die shortly after birth.
AB  - Neurotransmitter glutamate has been thought to derive mainly from glutamine via
      the action of glutaminase type 1 (GLS1). To address the importance of this
      pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion
      of a STOP cassette by homologous recombination produced a null allele that
      blocked transcription, encoded no immunoreactive protein, and abolished GLS1
      enzymatic activity. Null mutants were slightly smaller, were deficient in goal
      directed behavior, hypoventilated, and died in the first postnatal day. No gross
      or microscopic defects were detected in peripheral organs or in the CNS. In
      cultured neurons from the null mutants, miniature EPSC amplitude and duration
      were normal; however, the amplitude of evoked EPSCs decayed more rapidly with
      sustained 10 Hz stimulation, consistent with an observed reduction in
      depolarization-evoked glutamate release. Because of this activity-dependent
      impairment in glutamatergic transmission, we surmised that respiratory networks,
      which require temporal summation of synaptic input, would be particularly
      affected. We found that the amplitude of inspirations was decreased in vivo,
      chemosensitivity to CO2 was severely altered, and the frequency of pacemaker
      activity recorded in the respiratory generator in the pre-Botzinger complex, a
      glutamatergic brainstem network that can be isolated in vitro, was increased. Our
      results show that although alternate pathways to GLS1 glutamate synthesis support
      baseline glutamatergic transmission, the GLS1 pathway is essential for
      maintaining the function of active synapses, and thus the mutation is associated
      with impaired respiratory function, abnormal goal-directed behavior, and neonatal
      demise.

PMID- 16641248
TI  - Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome,
      after spinal cord injury in the adult rat.
AB  - Spinal cord injury (SCI) is a cause of major neurological disability, and no
      satisfactory treatment is currently available. Evidence suggests that
      polyunsaturated fatty acids (PUFAs) could target some of the pathological
      mechanisms that underlie damage after SCI. We examined the effects of treatment
      with PUFAs after lateral spinal cord hemisection in the rat. The omega-3 PUFAs
      alpha-linolenic acid and docosahexaenoic acid (DHA) injected 30 min after injury
      induced significantly improved locomotor performance and neuroprotection,
      including decreased lesion size and apoptosis and increased neuronal and
      oligodendrocyte survival. Evidence showing a decrease in RNA/DNA oxidation
      suggests that the neuroprotective effect of omega-3 PUFAs involved a significant
      antioxidant function. In contrast, animals treated with arachidonic acid, an
      omega-6 PUFA, had a significantly worse outcome than controls. We confirmed the
      neuroprotective effect of omega-3 PUFAs by examining the effects of DHA treatment
      after spinal cord compression injury. Results indicated that DHA administered 30
      min after spinal cord compression not only greatly increased survival of neurons
      but also resulted in significantly better locomotor performance for up to 6 weeks
      after injury. This report shows a striking difference in efficacy between the
      effects of treatment with omega-3 and omega-6 PUFAs on the outcome of SCI, with
      omega-3 PUFAs being neuroprotective and omega-6 PUFAs having a damaging effect.
      Given the proven clinical safety of omega-3 PUFAs, our observations show that
      these PUFAs have significant therapeutic potential in SCI. In contrast, the use
      of preparations enriched in omega-6 PUFAs after injury could worsen outcome after
      SCI.

PMID- 16641249
TI  - Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates.
AB  - Our recent studies show that chronic oral nicotine partially protects against
      striatal damage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated
      nonhuman primates. To identify the cellular changes associated with this
      protective action, we investigated the effects of nicotine treatment on stimulus
      evoked dopamine release, dopamine turnover, and synaptic plasticity in striatum
      from lesioned and unlesioned animals. Monkeys were chronically (6 months) treated
      with nicotine in the drinking water and subsequently lesioned with the
      dopaminergic neurotoxin MPTP (6 months) while nicotine was continued.
      Nigrostriatal damage increased nicotinic acetylcholine receptor (nAChR)-mediated
      fractional dopamine release from residual terminals, primarily through changes in
      alpha3*/alpha6* nAChRs. In contrast, fractional receptor-evoked dopamine release
      was similar to control in unlesioned and lesioned animals with chronic oral
      nicotine. Long-term nicotine administration also attenuated the enhanced K(+)
      evoked fractional dopamine release from synaptosomes of MPTP-lesioned animals,
      suggesting that nicotine treatment had a generalized effect on dopaminergic
      function. This premise was further supported by experiments showing that nicotine
      dosing decreased the elevated dopamine turnover that occurs after nigrostriatal
      damage. We next investigated changes in synaptic plasticity with lesioning and
      nicotine treatment. Nicotine treatment alone enhanced synaptic plasticity by
      lowering the threshold for long-term depression (LTD) in the corticostriatal
      pathway. MPTP lesioning led to a loss of LTD, a measure of short-term synaptic
      plasticity. In contrast, LTD was preserved in nicotine-treated lesioned animals.
      Thus, the present data show that the disruptions in striatal dopaminergic
      function after nigrostriatal damage were attenuated with chronic nicotine
      administration. These cellular alterations may underlie the ability of nicotine
      to maintain/restore normal function with nigrostriatal damage.

PMID- 16641250
TI  - Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine
      phosphorylation-dependent subunit trafficking.
AB  - Interactions between dopaminergic and glutamatergic afferents in the striatum are
      essential for motor learning and the regulation of movement. An important
      mechanism for these interactions is the ability of dopamine, through D1
      receptors, to potentiate NMDA glutamate receptor function. Here we show that, in
      striatal neurons, D1 receptor activation leads to rapid trafficking of NMDA
      receptor subunits, with increased NR1 and NR2B subunits in dendrites, enhanced
      coclustering of these subunits with the postsynaptic density scaffolding molecule
      postsynaptic density-95, and increased surface expression. The dopamine D1
      receptor-mediated NMDA receptor trafficking is blocked by an inhibitor of
      tyrosine kinases. Blockers of tyrosine phosphatases also induce NMDA subunit
      trafficking, but this effect is nonselective and alters both NR2A- and NR2B
      containing receptors. Furthermore, tyrosine phosphatase inhibition leads to the
      clustering of tyrosine-phosphorylated NR2B subunit along dendritic shafts. Our
      findings reveal that D1 receptor activation can potentiate striatal NMDA subunit
      function by directly promoting the surface insertion of the receptor complexes.
      This effect is regulated by the reciprocal actions of protein tyrosine
      phosphatases and tyrosine kinases. Modification of these pathways may be a useful
      therapeutic target for Parkinson's disease and other basal ganglia disorders in
      which abnormal function of striatal NMDA receptors contributes to the symptoms of
      the diseases.

PMID- 16641251
TI  - Reelin deficiency and displacement of mature neurons, but not neurogenesis,
      underlie the formation of granule cell dispersion in the epileptic hippocampus.
AB  - Mesio-temporal lobe epilepsy (MTLE) is often accompanied by granule cell
      dispersion (GCD), a widening of the granule cell layer. The molecular
      determinants of GCD are poorly understood. Here, we used an animal model to study
      whether GCD results from an increased dentate neurogenesis associated with an
      abnormal migration of the newly generated granule cells. Adult mice were given
      intrahippocampal injections of kainate (KA) known to induce focal epileptic
      seizures and GCD, comparable to the changes observed in human MTLE. Ipsilateral
      GCD progressively developed after KA injection and was paralleled by a gradual
      decrease in the expression of doublecortin, a marker of newly generated granule
      cells, in the dentate subgranular layer. Staining with Fluoro-Jade B revealed
      little cell degeneration in the subgranular layer on the KA-injected side.
      Labeling with bromodeoxyuridine showed an early, transient increase in mitotic
      activity in the dentate gyrus of the KA-injected hippocampus that gave rise to
      microglial cells and astrocytes but not to new neurons. Moreover, at later time
      points, there was a virtually complete cessation of mitotic activity in the
      injected hippocampus (where GCD continued to develop), but not on the
      contralateral side (where no GCD was observed). Finally, a significant decrease
      in reelin mRNA synthesis in the injected hippocampus paralleled the development
      of GCD, and neutralization of reelin by application of the CR-50 antibody induced
      GCD. These results show that GCD does not result from increased neurogenesis but
      reflects a displacement of mature granule cells, most likely caused by a local
      reelin deficiency.

PMID- 16641252
TI  - Individualizing chemotherapeutic treatment of colorectal cancer.
AB  - PURPOSE: Patient-specific factors that enter into decisions about the
      chemotherapy used to treat colorectal cancer are illustrated in several case
      studies. SUMMARY: Genetic polymorphisms in genes that encode drug-metabolizing
      enzymes may affect the disposition and the risk for toxicity from chemotherapy
      agents used to treat colorectal cancer. Severe toxicity from 5-fluorouracil has
      been attributed to a deficiency in dihydropyrimidine dehydrogenase (DPD), but
      currently there is no widely used genetic test for DPD deficiency. An assay is
      available for genotypic testing of the enzyme UGT1A1, which is predictive of
      toxicity from irinotecan. Advanced age, prior pelvic or abdominal radiotherapy, a
      poor performance status, and increased pretreatment total bilirubin concentration
      also are associated with irinotecan-related toxicity. A reduction in irinotecan
      dosage or use of an alternative agent may be warranted in patients with risk
      factors for toxicity. Positive epidermal growth factor receptor (EGFR) expression
      by immunohistochemical (IHC) staining does not necessarily predict the response
      to cetuximab, a monoclonal antibody that binds EGFR, possibly because of the low
      sensitivity of the test. Carcinoembryonic antigen (CEA) is the tumor marker of
      choice for monitoring for progression of colorectal cancer. CONCLUSION:
      Individualizing chemotherapy based on disease stage, pharmacogenetics, prior
      therapy, patient age, performance status, and CEA level may help to optimize
      outcomes from chemotherapy for patients with colorectal cancer.

PMID- 16641253
TI  - Impact of the Medicare Prescription Drug Improvement and Modernization Act on the
      management of colorectal cancer.
AB  - PURPOSE: The potential impact of changes in reimbursement for drugs and
      biologicals associated with the Medicare Prescription Drug Improvement and
      Modernization Act (MMA) on the management of colorectal cancer is described from
      the perspectives of health care providers and patients. SUMMARY: The introduction
      of new chemotherapeutic agents and supportive therapies over the past several
      decades has increased survival in patients with colorectal cancer. The changes in
      reimbursement for these therapies associated with MMA may affect the financial
      viability of private physician office practices and hospital-based outpatient
      clinics where such therapies are administered. The MMA-related changes also have
      the potential to decrease patient access to treatment and adversely affect
      treatment choices, scheduling, and outcomes. CONCLUSION: The reimbursement
      changes brought about by implementation of MMA could affect health care delivery
      and patient care.

PMID- 16641256
TI  - Evolving role of antineoplastic agents in colorectal cancer.
AB  - PURPOSE: The epidemiology, natural history, patient presentation, staging,
      prognosis, and treatment of colorectal cancer are described. SUMMARY: Colorectal
      cancer is a common malignancy that usually is not diagnosed when it is localized
      because it typically is asymptomatic in the early stages. Various cancer
      chemotherapeutic agents with different toxicities are available, including the
      recently introduced recombinant humanized immunoglobulin G(1) monoclonal
      antibodies cetuximab and bevacizumab. Chemotherapy may be used with or without
      surgery in patients with advanced or metastatic colorectal cancer, usually for
      palliation rather than a cure. The results of clinical trials suggest that
      patients with advanced or metastatic colorectal cancer probably should receive 5
      fluorouracil (5-FU)/leucovorin, irinotecan, oxaliplatin, bevacizumab, and
      cetuximab at some time in the course of treatment, although the preferred
      combinations and sequence of these agents remain to be determined. After surgery,
      adjuvant chemotherapy may be used for curative purposes in patients with stage
      III disease and some patients with stage II disease at high risk for disease
      recurrence and death. Although 5-FU plus leucovorin has been the standard
      adjuvant therapy, clinical trials have demonstrated that adding oxaliplatin or
      using capecitabine alone instead is an alternative. CONCLUSION: Several recently
      introduced chemotherapeutic agents appear promising for the treatment of
      colorectal cancer, but additional clinical research is needed to identify the
      ideal combinations and sequence of these agents.

PMID- 16641257
TI  - A tryptophan-rich motif in the carboxyl terminus of the small envelope protein of
      hepatitis B virus is central to the assembly of hepatitis delta virus particles.
AB  - The small hepatitis B virus surface antigen (S-HBsAg) is capable of driving the
      assembly and secretion of hepatitis delta virus (HDV) particles by interacting
      with the HDV ribonucleoprotein (RNP). Previously, a specific domain of the S
      HBsAg protein carboxyl terminus, including a tryptophan residue at position 196
      (W196), was proven essential for HDV maturation (S. Jenna and C. Sureau, J.
      Virol. 73: 3351-3358, 1999). Mutation of W196 to phenylalanine (W196F) was
      permissive for HBV subviral particle (SVP) secretion but deleterious to HDV
      virion assembly. Here, the W196F S-HBsAg deficiency was assigned to a loss of its
      ability for interaction with the large HDV antigen (L-HDAg), a major component of
      the RNP. Because the overall S-HBsAg carboxyl terminus is particularly rich in
      tryptophan, an amino acid frequently involved in protein-protein interactions,
      site-directed mutagenesis was conducted to investigate the function of the S
      HBsAg Trp-rich domain in HDV assembly. Single substitutions of tryptophan between
      positions 163 and 201 with alanine or phenylalanine were tolerated for SVP
      secretion, but those affecting W196, W199, and W201 were detrimental for HDV
      assembly. This was proven to result from a reduced capacity of the mutants for
      interaction with L-HDAg. In addition, a W196S S-HBsAg mutant, which has been
      described in HBV strains that arose in a few cases of lamivudine-treated HBV
      infected patients, was deficient for HDV assembly as a consequence of its
      impaired capacity for interacting with L-HDAg. Interestingly, the fact that even
      the most conservative substitution of phenylalanine for tryptophan at positions
      196, 199, or 201 was sufficient to ablate interaction of S-HBsAg with L-HDAg
      suggests that W196, W199, and W201 are located at a binding interface that is
      central to HDV maturation.

PMID- 16641258
TI  - Processing of the bovine spongiform encephalopathy-specific prion protein by
      dendritic cells.
AB  - Dendritic cells (DC) are suspected to be involved in transmissible spongiform
      encephalopathies, including bovine spongiform encephalopathy (BSE). We detected
      the disease-specific, protease-resistant prion protein (PrP(bse)) in splenic DC
      purified by magnetic cell sorting 45 days after intraperitoneal inoculation of
      BSE prions in immunocompetent mice. We showed that bone marrow-derived DC (BMDC)
      from wild-type or PrP-null mice acquired both PrP(bse) and prion infectivity
      within 2 h of in vitro culture with a BSE inoculum. BMDC cleared PrP(bse) within
      2 to 3 days of culture, while BMDC infectivity was only 10-fold diminished
      between days 1 and 6 of culture, suggesting that the infectious unit in BMDC is
      not removed at the same rate as PrP(bse) is removed from these cells. Bone marrow
      derived plasmacytoid DC and bone marrow-derived macrophages (BMM) also acquired
      and degraded PrP(bse) when incubated with a BSE inoculum, with kinetics very
      similar to those of BMDC. PrP(bse) capture is probably specific to antigen
      presenting cells since no uptake of PrP(bse) was observed when splenic B or T
      lymphocytes were incubated with a BSE inoculum in vitro. Lipopolysaccharide
      activation of BMDC or BMM prior to BSE infection resulted in an accelerated
      breakdown of PrP(bse). Injected by the intraperitoneal route, BMDC were not
      infectious for alymphoid recombination-activated gene 2(0)/common cytokine gamma
      chain-deficient mice, suggesting that these cells are not capable of directly
      propagating BSE infectivity to nerve endings.

PMID- 16641259
TI  - Identification of human papillomavirus type 16 L1 surface loops required for
      neutralization by human sera.
AB  - The variable surface loops on human papillomavirus (HPV) virions required for
      type-specific neutralization by human sera remain poorly defined. To determine
      which loops are required for neutralization, a series of hybrid virus-like
      particles (VLPs) were used to adsorb neutralizing activity from HPV type 16
      (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion
      neutralization assay. The hybrid VLPs used were composed of L1 sequences of
      either HPV16 or HPV31, on which one or two regions were replaced with homologous
      sequences from the other type. The regions chosen for substitution were the five
      known loops that form surface epitopes recognized by monoclonal antibodies and
      two additional variable regions between residues 400 and 450. Pretreatment of
      human sera, previously found to react to HPV16 VLPs in enzyme-linked
      immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the
      neutralizing epitopes reduced or eliminated the ability of sera to inhibit
      pseudovirus infection in vitro. Surprisingly, substitution of a single loop often
      ablated the ability of VLPs to adsorb neutralizing antibodies from human sera.
      However, for all sera tested, multiple surface loops were found to be important
      for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were
      most frequently identified as being essential for binding by neutralizing
      antibodies. These observations are consistent with the existence of multiple
      neutralizing epitopes on the HPV virion surface.

PMID- 16641260
TI  - Monomeric APOBEC3G is catalytically active and has antiviral activity.
AB  - APOBEC3G (APO3G) is a cytidine deaminase that restricts replication of vif
      defective human immunodeficiency virus type 1 (HIV-1). Like other members of the
      cellular deaminase family, APO3G has the propensity to form homo-multimers. In
      the current study, we investigated the functional determinants for
      multimerization of human APO3G and studied the role of APO3G multimerization for
      catalytic activity, virus encapsidation, and antiviral activity. We found that
      human APO3G is capable of forming multimeric complexes in transfected HeLa cells.
      Interestingly, multimerization of APO3G was exquisitely sensitive to RNase
      treatment, suggesting that interaction of APO3G subunits is facilitated or
      stabilized by an RNA bridge. Mutation of a conserved cysteine residue (C97) that
      is part of an N-terminal zinc-finger motif in APO3G abolished multimerization of
      APO3G; however, the C97 mutation inhibited neither in vitro deaminase activity
      nor antiviral function of APO3G. These results suggest that monomeric APO3G is
      both catalytically active and has antiviral activity. Interference studies
      employing either catalytically inactive or packaging-incompetent APO3G variants
      suggest that wild-type APO3G is packaged into HIV-1 particles in monomeric form.
      These results provide novel insights into the catalytic function and antiviral
      property of APO3G and demonstrate an important role for C97 in the RNA-dependent
      multimerization of this protein.

PMID- 16641261
TI  - Cyclophilin A renders human immunodeficiency virus type 1 sensitive to Old World
      monkey but not human TRIM5 alpha antiviral activity.
AB  - TRIM5alpha is an important mediator of antiretroviral innate immunity influencing
      species-specific retroviral replication. Here we investigate the role of the
      peptidyl prolyl isomerase enzyme cyclophilin A in TRIM5alpha antiviral activity.
      Cyclophilin A is recruited into nascent human immunodeficiency virus type 1 (HIV
      1) virions as well as incoming HIV-1 capsids, where it isomerizes an exposed
      proline residue. Here we show that cyclophilin A renders HIV-1 sensitive to
      restriction by TRIM5alpha in cells from Old World monkeys, African green monkey
      and rhesus macaque. Inhibition of cyclophilin A activity with cyclosporine A, or
      reducing cyclophilin A expression with small interfering RNA, rescues TRIM5alpha
      restricted HIV-1 infectivity. The effect of cyclosporine A on HIV-1 infectivity
      is dependent on TRIM5alpha expression, and expression of simian TRIM5alpha in
      permissive feline cells renders them able to restrict HIV-1 in a cyclosporine A
      sensitive way. We use an HIV-1 cyclophilin A binding mutant (CA G89V) to show
      that cyclophilin A has different roles in restriction by Old World monkey
      TRIM5alpha and owl monkey TRIM-Cyp. TRIM-Cyp, but not TRIM5alpha, recruits its
      tripartite motif to HIV-1 capsid via cyclophilin A and, therefore, HIV-1 G89V is
      insensitive to TRIM-Cyp but sensitive to TRIM5alpha. We propose that cyclophilin
      A isomerization of a proline residue in the TRIM5alpha sensitivity determinant of
      the HIV-1 capsid sensitizes it to restriction by Old World monkey TRIM5alpha. In
      humans, where HIV-1 has adapted to bypass TRIM5alpha activity, the effects of
      cyclosporine A are independent of TRIM5alpha. We speculate that cyclophilin A
      alters HIV-1 sensitivity to a TRIM5alpha-independent innate immune pathway in
      human cells.

PMID- 16641262
TI  - Effects of mutations in the human immunodeficiency virus type 1 Gag gene on RNA
      packaging and recombination.
AB  - Human immunodeficiency virus type 1 (HIV-1) recombination occurs during reverse
      transcription when parts of the two co-packaged RNAs are used as templates for
      DNA synthesis. It was previously hypothesized that HIV-1 Gag polyproteins
      preferentially encapsidate the RNA from which they were translated (cis-packaging
      hypothesis). This hypothesis implies that mutants encoding Gag that cannot
      efficiently package viral RNA are selected against at two levels: these mutants
      do not generate infectious virus, and these mutants are not efficiently rescued
      by the wild-type virus because the mutant RNAs are packaged at much lower levels
      than are those of the wild-type genome. Therefore, genetic information encoded by
      gag mutants can be rapidly lost in the viral population. To test this prediction
      of the cis-packaging hypothesis, we examined several gag mutants by measuring the
      efficiencies of the mutant RNAs in being packaged in trans in the presence of
      wild-type virus and determining the rates of recombination between gag mutants
      and wild-type viruses. We observed that the viral RNAs from the nucleocapsid zinc
      finger or the capsid truncation mutant were packaged efficiently in trans, and
      these mutant viruses also frequently recombined with the wild-type viruses. In
      contrast, viral RNAs from mutants containing a 6-nucleotide substitution
      encompassing the gag AUG were not efficiently encapsidated, resulting in a low
      rate of recombination between the mutants and wild-type viruses. Further analyses
      revealed that other, more subtle mutations changing the gag AUG and abolishing
      Gag translation did not interfere with efficient encapsidation of the mutant RNA.
      Our results indicated that neither the gag AUG sequence nor Gag translation is
      essential for viral RNA encapsidation, and Gag can package both wild-type and gag
      mutant RNAs with similar efficiencies. Therefore, we propose that HIV-1 RNA
      encapsidation occurs mainly in trans, and most gag mutants can be rescued by wild
      type virus; therefore, they are unlikely to face the aforementioned double
      negative selection.

PMID- 16641263
TI  - A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C
      based on envelope V3 sequences.
AB  - In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the
      emergence of viruses able to use CXCR4 as a coreceptor is well documented and
      associated with accelerated CD4 decline and disease progression. However, in HIV
      1 subtype C infections, responsible for more than 50% of global infections, CXCR4
      usage is less common, even in individuals with advanced disease. A reliable
      phenotype prediction method based on genetic sequence analysis could provide a
      rapid and less expensive approach to identify possible CXCR4 variants and thus
      increase our understanding of subtype C coreceptor usage. For subtype B V3 loop
      sequences, genotypic predictors have been developed based on position-specific
      scoring matrices (PSSM). In this study, we apply this methodology to a training
      set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing
      [NSI] CCR5(+) and 51 SI CXCR4(+) sequences) to derive a C-PSSM predictor.
      Specificity and sensitivity distributions were estimated by combining data set
      bootstrapping with leave-one-out cross-validation, with random sampling of single
      sequences from individuals on each bootstrap iteration. The C-PSSM had an
      estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a
      sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than
      predictions based on other methods, including a commonly used method based on the
      presence of positively charged residues (sensitivity, 47.8%). A specificity of
      83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47
      NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops
      as existing subtype B-specific methods do on subtype B V3 loops. We present
      bioinformatic evidence that particular sites may influence coreceptor usage
      differently, depending on the subtype.

PMID- 16641264
TI  - Expansion and diversification of virus-specific T cells following immunization of
      human immunodeficiency virus type 1 (HIV-1)-infected individuals with a
      recombinant modified vaccinia virus Ankara/HIV-1 Gag vaccine.
AB  - Affordable therapeutic strategies that induce sustained control of human
      immunodeficiency virus type 1 (HIV-1) replication and are tailored to the
      developing world are urgently needed. Since CD8(+) and CD4(+) T cells are crucial
      to HIV-1 control, stimulation of potent cellular responses by therapeutic
      vaccination might be exploited to reduce antiretroviral drug exposure. However,
      therapeutic vaccines tested to date have shown modest immunogenicity. In this
      study, we performed a comprehensive analysis of the changes in virus-specific
      CD8(+) and CD4(+) T-cell responses occurring after vaccination of 16 HIV-1
      infected individuals with a recombinant modified vaccinia virus Ankara-vectored
      vaccine expressing the consensus HIV-1 clade A Gag p24/p17 sequences and multiple
      CD8(+) T-cell epitopes during highly active antiretroviral therapy. We observed
      significant amplification and broadening of CD8(+) and CD4(+) gamma interferon
      responses to vaccine-derived epitopes in the vaccinees, without rebound viremia,
      but not in two unvaccinated controls followed simultaneously. Vaccine-driven
      CD8(+) T-cell expansions were also detected by tetramer reactivity, predominantly
      in the CD45RA(-) CCR7(+) or CD45RA(-) CCR7(-) compartments, and persisted for at
      least 1 year. Expansion was associated with a marked but transient up-regulation
      of CD38 and perforin within days of vaccination. Gag-specific CD8(+) and CD4(+) T
      cell proliferation also increased postvaccination. These data suggest that
      immunization with MVA.HIVA is a feasible strategy to enhance potentially
      protective T-cell responses in individuals with chronic HIV-1 infection.

PMID- 16641265
TI  - Induction of multifunctional human immunodeficiency virus type 1 (HIV-1)-specific
      T cells capable of proliferation in healthy subjects by using a prime-boost
      regimen of DNA- and modified vaccinia virus Ankara-vectored vaccines expressing
      HIV-1 Gag coupled to CD8+ T-cell epitopes.
AB  - A double-blind randomized phase I trial was conducted in human immunodeficiency
      virus type 1 (HIV-1)-negative subjects receiving vaccines vectored by plasmid DNA
      and modified vaccinia virus Ankara (MVA) expressing HIV-1 p24/p17 gag linked to a
      string of CD8(+) T-cell epitopes. The trial had two groups. One group received
      either two doses of MVA.HIVA (2x MVA.HIVA) (n=8) or two doses of placebo (2x
      placebo) (n=4). The second group received 2x pTHr.HIVA followed by one dose of
      MVA.HIVA (n=8) or 3x placebo (n=4). In the pTHr.HIVA-MVA.HIVA group, HIV-1
      specific T-cell responses peaked 1 week after MVA.HIVA vaccination in both ex
      vivo gamma interferon (IFN-gamma) ELISPOT (group mean, 210 spot-forming
      cells/10(6) cells) and proliferation (group mean stimulation index, 37), with
      assays detecting positive responses in four out of eight and five out of eight
      subjects, respectively. No HIV-1-specific T-cell responses were detected in
      either assay in the 2x MVA.HIVA group or subjects receiving placebo. Using a
      highly sensitive and reproducible cultured IFN-gamma ELISPOT assay, positive
      responses mainly mediated by CD4(+) T cells were detected in eight out of eight
      vaccinees in the pTHr.HIVA-MVA.HIVA group and four out of eight vaccinees in the
      2x MVA.HIVA group. Importantly, no false-positive responses were detected in the
      eight subjects receiving placebo. Of the 12 responders, 11 developed responses to
      previously identified immunodominant CD4(+) T-cell epitopes, with 6 volunteers
      having responses to more than one epitope. Five out of 12 responders also
      developed CD8(+) T-cell responses to the epitope string. Induced T cells produced
      a variety of anti-viral cytokines, including tumor necrosis factor alpha and
      macrophage inflammatory protein 1 beta. These data demonstrate that prime-boost
      vaccination with recombinant DNA and MVA vectors can induce multifunctional HIV-1
      specific T cells in the majority of vaccinees.

PMID- 16641266
TI  - NS1 interaction with CKII alpha: novel protein complex mediating parvovirus
      induced cytotoxicity.
AB  - During a productive infection, the prototype strain of the parvovirus minute
      virus of mice (MVMp) induces dramatic morphological alterations in permissive A9
      fibroblasts, culminating in cell lysis at the end of infection. These cytopathic
      effects (CPE) result from rearrangements and destruction of the cytoskeletal
      micro- and intermediate filaments, while other structures such as the nuclear
      lamina and particularly the microtubule network remain protected throughout the
      infection (J. P. F. Nuesch et al., Virology 331:159-174, 2005). In order to
      unravel the mechanism(s) by which parvoviruses trigger CPE, we searched for NS1
      interaction partners by differential affinity chromatography, using distinct NS1
      mutants debilitated specifically for this function. Thereby, we isolated an NS1
      partner polypeptide, whose interaction with NS1 correlated with the competence of
      the viral product for CPE induction, and further identified it by tandem mass
      spectrometry and Western blotting analyses to consist of the catalytic subunit of
      casein kinase II, CKIIalpha. This interaction of NS1 with CKIIalpha suggested
      interference by the viral protein with intracellular signaling. Using permanent
      cell lines expressing dominant-negative CKIIalpha mutants, we were able to show
      that this kinase activity was indeed specifically involved in parvoviral CPE and
      progeny particle release. Furthermore, the NS1/CKIIalpha complex proved to be
      able to specifically phosphorylate viral capsids, indicating a mediator function
      of NS1 for CKII activity and specificity, at least in vitro. Altogether our data
      suggest that parvovirus-induced CPE is mediated by NS1 interference with
      intracellular CKII signaling.

PMID- 16641267
TI  - Virucidal activity of a GT-rich oligonucleotide against herpes simplex virus
      mediated by glycoprotein B.
AB  - We have investigated the antiviral mechanism of a phosphorothioate
      oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV)
      in the low micromolar range in plaque reduction assays. We isolated a mutant that
      is resistant to this compound. Marker rescue and sequencing experiments showed
      that resistance was due to at least one of three mutations in the UL27 gene which
      result in amino acid changes in glycoprotein B (gB). Because gB has a role in
      attachment and entry of HSV, we tested the effects of ISIS 5652 at these stages
      of infection. The oligonucleotide potently inhibited attachment of virus to cells
      at 4 degrees C; however, the resistant mutant did not exhibit resistance at this
      stage. Moreover, a different oligonucleotide with little activity in plaque
      reduction assays was as potent as ISIS 5652 in inhibiting attachment. Similarly,
      ISIS 5652 was able to inhibit entry of pre-attached virions into cells at 37
      degrees C, but the mutant did not exhibit resistance in this assay. The mutant
      did not attach to or enter cells more quickly than did wild-type virus.
      Strikingly, incubation of wild-type virus with 1 to 2 microM ISIS 5652 at 37
      degrees C led to a time-dependent, irreversible loss of infectivity (virucidal
      activity). No virucidal activity was detected at 4 degrees C or with an unrelated
      oligonucleotide at 37 degrees C. The resistant mutant and a marker-rescued
      derivative containing its gB mutations exhibited substantial resistance to this
      virucidal activity of ISIS 5652. We hypothesize that the GT-rich oligonucleotide
      induces a conformational change in gB that results in inactivation of
      infectivity.

PMID- 16641268
TI  - In vivo interactions of ecotropic and polytropic murine leukemia viruses in mixed
      retrovirus infections.
AB  - Mixed retrovirus infections are the rule rather than the exception in mice and
      other species, including humans. Interactions of retroviruses in mixed infections
      and their effects on disease induction are poorly understood. Upon infection of
      mice, ecotropic retroviruses recombine with endogenous proviruses to generate
      polytropic viruses that utilize different cellular receptors. Interactions among
      the retroviruses of this mixed infection facilitate disease induction. Using mice
      infected with defined mixtures of the ecotropic Friend murine leukemia virus (F
      MuLV) and different polytropic viruses, we demonstrate several dramatic effects
      of mixed infections. Remarkably, inoculation of F-MuLV with polytropic MuLVs
      completely suppressed the generation of new recombinant viruses and dramatically
      altered disease induction. Co-inoculation of F-MuLV with one polytropic virus
      significantly lengthened survival times, while inoculation with another
      polytropic MuLV induced a rapid and severe neurological disease. In both
      instances, the level of the polytropic MuLV was increased 100- to 1,000-fold,
      whereas the ecotropic MuLV level remained unchanged. Surprisingly, nearly all of
      the polytropic MuLV genomes were packaged within F-MuLV virions (pseudotyped)
      very soon after infection. At this time, only a fractional percentage of cells in
      the mouse were infected by either virus, indicating that the co-inoculated
      viruses had infected the same small subpopulation of susceptible cells. The
      profound amplification of polytropic MuLVs in coinfected mice may be facilitated
      by pseudotyping or, alternatively, by transactivation of the polytropic virus in
      the coinfected cells. This study illustrates the complexity of the interactions
      between components of mixed retrovirus infections and the dramatic effects of
      these interactions on disease processes.

PMID- 16641270
TI  - DC-SIGN facilitates fusion of dendritic cells with human T-cell leukemia virus
      type 1-infected cells.
AB  - Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1
      (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that
      monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1
      infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing
      nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced
      syncytium formation. DC-SIGN is known to bind with high affinity to various viral
      envelope glycoproteins, including human immunodeficiency virus (HIV) and
      hepatitis C virus, as well as to the cellular receptors ICAM-2 and ICAM-3. After
      cocultivating DCs and HTLV-1-infected cells, we found that anti-DC-SIGN
      monoclonal antibodies (MAbs) were able to decrease the number and size of HTLV-1
      induced syncytia. Moreover, expression of the lectin in epithelial-cell lines
      dramatically enhanced the ability to fuse with HTLV-1-positive cells.
      Interestingly, in contrast to the envelope (Env) glycoproteins of HIV and other
      viruses, that of HTLV-1 does not bind directly to DC-SIGN. The facilitating role
      of the lectin in HTLV-1 syncytium formation is mediated by its interaction with
      ICAM-2 and ICAM-3, as demonstrated by use of MAbs directed against these adhesion
      molecules. Altogether, our results indicate that DC-SIGN facilitates HTLV-1
      infection and fusion of DCs through an ICAM-dependent mechanism.

PMID- 16641269
TI  - Neutralizing antibodies do not mediate suppression of human immunodeficiency
      virus type 1 in elite suppressors or selection of plasma virus variants in
      patients on highly active antiretroviral therapy.
AB  - Neutralizing antibodies (NAb) against autologous virus can reach high titers in
      human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive
      disease. Less is known about the role of NAb in HIV-1-infected patients with
      viral loads of <50 copies/ml of plasma, including patients on effective highly
      active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1
      replication without antiretroviral therapy. In this study, we analyzed full
      length env sequences from plasma viruses and proviruses in resting CD4(+) T cells
      of HAART-treated patients, elite suppressors, and untreated HIV-1-infected
      patients with progressive disease. For each patient group, we assessed plasma
      virus neutralization by autologous, contemporaneous plasma. The degree of env
      diversity, the number of N-linked glycosylation sites, and the lengths of
      variable loops were all lower in elite suppressors than in HAART-treated and
      untreated viremic patients. Both elite suppressors and HAART-treated patients had
      lower titers of NAb against HIV-1 lab strains than those of untreated viremic
      patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma
      viruses were similarly low in chronic progressors, elite suppressors, and HAART
      treated patients. In elite suppressors and HAART-treated patients, titers of NAb
      against autologous plasma viruses also did not differ significantly from titers
      against autologous proviruses from resting CD4(+) T cells. These results suggest
      that high-titer NAb are not required for maintenance of viral suppression in
      elite suppressors and that NAb do not select plasma virus variants in most HAART
      treated patients. Both drug-mediated and natural suppression of HIV-1 replication
      to levels below 50 copies/ml may limit the stimulation and maintenance of
      effective NAb responses.

PMID- 16641271
TI  - Tax interacts with P-TEFb in a novel manner to stimulate human T-lymphotropic
      virus type 1 transcription.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) encodes a transcriptional activator,
      Tax, whose function is essential for viral transcription and replication. Tax
      transactivates the viral long-terminal repeat through a series of protein-protein
      interactions which facilitate CREB and CBP/p300 binding. In addition, Tax
      dissociates transcription repressor histone deacetylase 1 interaction with the
      CREB response element. The subsequent events through which Tax interacts and
      communicates with RNA polymerase II and cyclin-dependent kinases (CDKs) are not
      clearly understood. Here we present evidence that Tax recruits positive
      transcription elongation factor b (P-TEFb) (CDK9/cyclin T1) to the viral
      promoter. This recruitment likely involves protein-protein interactions since Tax
      associates with P-TEFb in vitro as demonstrated by glutathione S-transferase
      fusion protein pull-down assays and in vivo as shown by co-immunoprecipitation
      assays. Functionally, small interfering RNA directed toward CDK9 inhibited Tax
      transactivation in transient assays. Consistent with these findings, the
      depletion of CDK9 from nuclear extracts inhibited Tax transactivation in vitro.
      Reconstitution of the reaction with wild-type P-TEFb, but not a kinase-dead
      mutant, recovered HTLV-1 transcription. Moreover, the addition of the CDK9
      inhibitor flavopiridol blocked Tax transactivation in vitro and in vivo.
      Interestingly, we found that Tax regulates CDK9 kinase activity through a novel
      autophosphorylation pathway.

PMID- 16641272
TI  - Dynamic localization of the human papillomavirus type 11 origin binding protein
      E2 through mitosis while in association with the spindle apparatus.
AB  - Papillomaviral DNA replicates as extrachromosomal plasmids in squamous
      epithelium. Viral DNA must segregate equitably into daughter cells to persist in
      dividing basal/parabasal cells. We have previously reported that the viral origin
      binding protein E2 of human papillomavirus types 11 (HPV-11), 16, and 18
      colocalized with the mitotic spindles. In this study, we show the localization of
      the HPV-11 E2 protein to be dynamic. It colocalized with the mitotic spindles
      during prophase and metaphase. At anaphase, it began to migrate to the central
      spindle microtubules, where it remained through telophase and cytokinesis. It was
      additionally observed in the midbody at cytokinesis. A peptide spanning residues
      285 to 308 in the carboxyl-terminal domain of HPV-11 E2 (E2C) is necessary and
      sufficient to confer localization on the mitotic spindles. This region is
      conserved in HPV-11, -16, and -18 and bovine papillomavirus type 4 (BPV-4) E2 and
      is also required for the respective E2C to colocalize with the mitotic spindles.
      The E2 protein of bovine papillomavirus type 1 is tethered to the mitotic
      chromosomes via the cellular protein Brd4. However, the HPV-11 E2 protein did not
      associate with Brd4 during mitosis. Lastly, a chimeric BPV-1 E2C containing the
      spindle localization domain from HPV-11 E2C gained the ability to localize to the
      mitotic spindles, whereas the reciprocal chimera lost the ability. We conclude
      that this region of HPV E2C is critical for localization with the mitotic
      apparatus, enabling the HPV DNA to sustain persistent infections.

PMID- 16641273
TI  - Lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus
      infection.
AB  - Cytomegalovirus (CMV) poses a threat to the therapy of hematopoietic malignancies
      by hematopoietic stem cell transplantation, but efficient reconstitution of
      antiviral immunity prevents CMV organ disease. Tumor relapse originating from a
      minimal residual leukemia poses another threat. Although a combination of risk
      factors was supposed to enhance the incidence and severity of transplantation
      associated disease, a murine model of a liver-adapted B-cell lymphoma has
      previously shown a survival benefit and tumor growth inhibition by nonlethal
      subcutaneous infection with murine CMV. Here we have investigated the underlying
      antitumoral mechanism. Virus replication proved to be required, since inactivated
      virions or the highly attenuated enhancerless mutant mCMV-DeltaMIEenh did not
      impact the lymphoma in the liver. Surprisingly, the dissemination-deficient
      mutant mCMV-DeltaM36 inhibited tumor growth, even though this virus fails to
      infect the liver. On the other hand, various strains of herpes simplex viruses
      consistently failed to control the lymphoma, even though they infect the liver. A
      quantitative analysis of the tumor growth kinetics identified a transient tumor
      remission by apoptosis as the antitumoral effector mechanism. Tumor cell colonies
      with cells surviving the CMV-induced "apoptotic crisis" lead to tumor relapse
      even in the presence of full-blown tissue infection. Serial transfer of surviving
      tumor cells did not indicate a selection of apoptosis-resistant genetic variants.
      NK cell activity of CD49b-expressing cells failed to control the lymphoma upon
      adoptive transfer. We propose the existence of an innate antitumoral mechanism
      that is triggered by CMV infection and involves an apoptotic signal effective at
      a distant site of tumor growth.

PMID- 16641274
TI  - Rotavirus viremia and extraintestinal viral infection in the neonatal rat model.
AB  - Rotaviruses infect mature, differentiated enterocytes of the small intestine and,
      by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The
      neonatal rat model of rotavirus infection was used to determine the kinetics of
      viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day
      old rat pups were inoculated intragastrically with an animal (RRV) or human
      (HAL1166) rotavirus or phosphate-buffered saline. Blood was collected from a
      subset of rat pups, and following perfusion to remove residual blood, organs were
      removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked
      immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed
      in formalin for histology and immunohistochemistry. Viremia was detected
      following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose
      was 1.8 x 10(3) PFU, and the 50% diarrhea dose was 7.7 x 10(5) PFU, indicating
      that infection and viremia occurred in the absence of diarrhea and that detecting
      rotavirus antigen in the blood was a more sensitive measure of infection than
      diarrhea. Rotavirus antigens and infectious virus were detected in multiple
      organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus, and
      bladder). Histopathological changes due to rotavirus infection included acute
      inflammation of the portal tract and bile duct, microsteatosis, necrosis, and
      inflammatory cell infiltrates in the parenchymas of the liver and lungs.
      Colocalization of structural and nonstructural proteins with histopathology in
      the liver and lungs indicated that the histological changes observed were due to
      rotavirus infection and replication. Replicating rotavirus was also detected in
      macrophages in the lungs and blood vessels, indicating a possible mechanism of
      rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea,
      was observed in the presence of passively or actively acquired rotavirus-specific
      antibody. These findings alter the previously accepted concept of rotavirus
      pathogenesis to include not only gastroenteritis but also viremia, and they
      indicate that rotavirus could cause a broad array of systemic diseases in a
      number of different organs.

PMID- 16641275
TI  - Long-term-infected telomerase-immortalized endothelial cells: a model for
      Kaposi's sarcoma-associated herpesvirus latency in vitro and in vivo.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's
      sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's
      disease. Most KS tumor cells are latently infected with KSHV and are of
      endothelial origin. While PEL-derived cell lines maintain KSHV indefinitely, all
      KS tumor-derived cells to date have lost viral genomes upon ex vivo cultivation.
      To study KSHV latency and tumorigenesis in endothelial cells, we generated
      telomerase-immortalized human umbilical vein endothelial (TIVE) cells. TIVE cells
      express all KSHV latent genes 48 h postinfection, and productive lytic
      replication could be induced by RTA/Orf50. Similar to prior models, infected
      cultures gradually lost viral episomes. However, we also obtained, for the first
      time, two endothelial cell lines in which KSHV episomes were maintained
      indefinitely in the absence of selection. Long-term KSHV maintenance correlated
      with loss of reactivation in response to RTA/Orf50 and complete oncogenic
      transformation. Long-term-infected TIVE cells (LTC) grew in soft agar and
      proliferated under reduced-serum conditions. LTC, but not parental TIVE cells,
      formed tumors in nude mice. These tumors expressed high levels of the latency
      associated nuclear antigen (LANA) and expressed lymphatic endothelial specific
      antigens as found in KS (LYVE-1). Furthermore, host genes, like those encoding
      interleukin 6, vascular endothelial growth factor, and basic fibroblast growth
      factor, known to be highly expressed in KS lesions were also induced in LTC
      derived tumors. KSHV-infected LTCs represent the first xenograft model for KS and
      should be of use to study KS pathogenesis and for the validation of anti-KS drug
      candidates.

PMID- 16641276
TI  - African swine fever virus protein pE296R is a DNA repair apurinic/apyrimidinic
      endonuclease required for virus growth in swine macrophages.
AB  - We show here that the African swine fever virus (ASFV) protein pE296R, predicted
      to be a class II apurinic/apyrimidinic (AP) endonuclease, possesses
      endonucleolytic activity specific for AP sites. Biochemical characterization of
      the purified recombinant enzyme indicated that the K(m) and catalytic efficiency
      values for the endonucleolytic reaction are in the range of those reported for
      Escherichia coli endonuclease IV (endo IV) and human Ape1. In addition to
      endonuclease activity, the ASFV enzyme has a proofreading 3'-->5' exonuclease
      activity that is considerably more efficient in the elimination of a mismatch
      than in that of a correctly paired base. The three-dimensional structure
      predicted for the pE296R protein underscores the structural similarities between
      endo IV and the viral protein, supporting a common mechanism for the cleavage
      reaction. During infection, the protein is expressed at early times and
      accumulates at later times. The early enzyme is localized in the nucleus and the
      cytoplasm, while the late protein is found only in the cytoplasm. ASFV carries
      two other proteins, DNA polymerase X and ligase, that, together with the viral AP
      endonuclease, could act as a viral base excision repair system to protect the
      virus genome in the highly oxidative environment of the swine macrophage, the
      virus host cell. Using an ASFV deletion mutant lacking the E296R gene, we have
      determined that the viral endonuclease is required for virus growth in
      macrophages but not in Vero cells. This finding supports the existence of a viral
      reparative system to maintain virus viability in the infected macrophage.

PMID- 16641277
TI  - Simian immunodeficiency virus SIVagm.sab infection of Caribbean African green
      monkeys: a new model for the study of SIV pathogenesis in natural hosts.
AB  - Caribbean-born African green monkeys (AGMs) were classified as Chlorocebus
      sabaeus by cytochrome b sequencing. Guided by these phylogenetic analyses, we
      developed a new model for the study of simian immunodeficiency virus (SIV)
      infection in natural hosts by inoculating Caribbean AGMs with their species
      specific SIVagm.sab. SIVagm.sab replicated efficiently in Caribbean AGM
      peripheral blood mononuclear cells in vitro. During SIVagm.sab primary infection
      of six Caribbean AGMs, the virus replicated at high levels, with peak viral loads
      (VLs) of 10(7) to 10(8) copies/ml occurring by day 8 to 10 postinfection (p.i.).
      Set-point values of up to 2 x 10(5) copies/ml were reached by day 42 p.i. and
      maintained throughout follow-up (through day 450 p.i.). CD4(+) T-cell counts in
      the blood showed a transient depletion at the peak of VL, and then returned to
      near preinfection values by day 28 p.i. and remained relatively stable during the
      chronic infection. Preservation of CD4 T cells was also found in lymph nodes
      (LNs) of chronic SIVagm.sab-infected Caribbean AGMs. No activation of CD4(+) T
      cells was detected in the periphery in SIV-infected Caribbean AGMs. These
      virological and immunological profiles from peripheral blood and LNs were
      identical to those previously reported in African-born AGMs infected with the
      same viral strain (SIVagm.sab92018). Due to these similarities, we conclude that
      Caribbean AGMs are a useful alternative to AGMs of African origin as a model for
      the study of SIV infection in natural African hosts.

PMID- 16641278
TI  - Comparison of simian immunodeficiency virus SIVagmVer replication and CD4+ T-cell
      dynamics in vervet and sabaeus African green monkeys.
AB  - The simian immunodeficiency viruses (SIV) naturally infect a wide range of
      African primates, including African green monkeys (AGM). Despite moderate to high
      levels of plasma viremia in naturally infected AGM, infection is not associated
      with immunodeficiency. We recently reported that SIVagmVer90 isolated from a
      naturally infected vervet AGM induced AIDS following experimental inoculation of
      pigtailed macaques. The goal of the present study was to evaluate the replication
      of this isolate in two species of AGM, sabaeus monkeys (Chlorocebus sabaeus) and
      vervets (C. pygerythrus). Inoculation of sabaeus AGM with SIVagmVer90 resulted in
      low and variable primary and set-point viremia (<10(2) to 10(4) copies/ml). In
      contrast, inoculation of vervet AGM with either SIVagmVer90 or blood from a
      naturally infected vervet (Ver1) resulted in high primary viremia and moderate
      plateau levels, similar to the range seen in naturally infected vervets from this
      cohort. CD4(+) T cells remained stable throughout infection, even in AGM with
      persistent high viremia. Despite the lack of measurable lymphadenopathy,
      infection was associated with an increased number of Ki-67(+) T cells in lymph
      node biopsies, consistent with an early antiviral immune response. The
      preferential replication of SIVagmVer in vervet versus sabaeus AGM shows that it
      is critical to match AGM species and SIV strains for experimental models of
      natural SIV infection.

PMID- 16641279
TI  - N-glycans on Nipah virus fusion protein protect against neutralization but reduce
      membrane fusion and viral entry.
AB  - Nipah virus (NiV) is a deadly emerging paramyxovirus. The NiV attachment (NiV-G)
      and fusion (NiV-F) envelope glycoproteins mediate both syncytium formation and
      viral entry. Specific N-glycans on paramyxovirus fusion proteins are generally
      required for proper conformational integrity and biological function. However,
      removal of individual N-glycans on NiV-F had little negative effect on processing
      or fusogenicity and has even resulted in slightly increased fusogenicity. Here,
      we report that in both syncytium formation and viral entry assays, removal of
      multiple N-glycans on NiV-F resulted in marked increases in fusogenicity (>5
      fold) but also resulted in increased sensitivity to neutralization by NiV-F
      specific antisera. The mechanism underlying the hyperfusogenicity of these NiV-F
      N-glycan mutants is likely due to more-robust six-helix bundle formation, as
      these mutants showed increased fusion kinetics and were more resistant to
      neutralization by a fusion-inhibitory reagent based on the C-terminal heptad
      repeat region of NiV-F. Finally, we demonstrate that the fusogenicities of the
      NiV-F N-glycan mutants were inversely correlated with the relative avidities of
      NiV-F's interactions with NiV-G, providing support for the attachment protein
      "displacement" model of paramyxovirus fusion. Our results indicate that N-glycans
      on NiV-F protect NiV from antibody neutralization, suggest that this "shielding"
      role comes together with limiting cell-cell fusion and viral entry efficiencies,
      and point to the mechanisms underlying the hyperfusogenicity of these N-glycan
      mutants. These features underscore the varied roles that N-glycans on NiV-F play
      in the pathobiology of NiV entry but also shed light on the general mechanisms of
      paramyxovirus fusion with host cells.

PMID- 16641280
TI  - Cottontail rabbit papillomavirus E8 protein is essential for wart formation and
      provides new insights into viral pathogenesis.
AB  - The cottontail rabbit papillomavirus (CRPV) a and b subtypes display a conserved
      E8 open reading frame encoding a 50-amino-acid hydrophobic protein, with
      structural similarities to the E5 transmembrane oncoprotein of genital human PVs
      (HPVs). CRPV E8 has been reported to play a role in papilloma growth but not to
      be essential in papilloma formation. Here we report that the knockout of E8 start
      codon almost prevented wart induction upon biobalistic inoculation of viral DNA
      onto rabbit skin. The scarce warts induced showed very slow growth, despite
      sustained expression of E6 and E7 oncogenes. This points to an essential role of
      E8 in disturbing epidermal homeostasis. Using a yeast two-hybrid screen, we found
      that E8 interacted with the zinc transporter ZnT1, protocadherin 1 (PCDH1), and
      AHNAK/desmoyokin, three proteins as yet unrelated to viral pathogenesis or cell
      transformation. HPV16 E5 also interacted with these proteins in two-hybrid assay.
      CRPV E8 mainly localized to the Golgi apparatus and the early endosomes of
      transfected keratinocytes and colocalized with ZnT1, PCDH1, and AHNAK. We showed
      that ZnT1 and PCDH1 formed a complex and that E8 disrupted this complex. CRPV E8,
      like HPV16 E5, increased epidermal growth factor (EGF)-dependent extracellular
      signal-regulated kinase 1/2 (ERK1/2) phosphorylation and both the EGF-dependent
      and the EGF-independent activity of activating protein-1 (AP-1). Competition
      experiments with a nonfunctional truncated ZnT1 protein showed that E8-ZnT1
      interaction was required for AP-1 activation. Our data identify CRPV E8 as a key
      player in papilloma induction and unravel novel cellular targets for inducing the
      proliferation of keratinocytes.

PMID- 16641281
TI  - Receptor-independent infection of murine coronavirus: analysis by spinoculation.
AB  - A highly neurovirulent murine coronavirus JHMV (wild-type [wt] JHMV) is known to
      spread from cells infected via the murine coronavirus mouse hepatitis virus
      receptor (MHVR) to cells without MHVR (MHVR-independent infection), whereas a
      mutant virus isolated from wt JHMV, srr7, spread only in an MHVR-dependent
      fashion. These observations were obtained by the overlay of JHMV-infected cells
      onto receptor-negative cells that are otherwise resistant to wt JHMV infection.
      MHVR-independent infection is hypothetically thought to be attributed to a
      naturally occurring fusion activation of the wt JHMV S protein, which did not
      occur in the case of srr7. Attachment of S protein on cells without MHVR during
      the S-protein activation process seems to be a key condition. Thus, in the
      present study, we tried to see whether wt JHMV virions that are attached on MHVR
      negative cells are able to infect those cells. In order to make virions attach to
      the cell surface without MHVR, we have used spinoculation, namely, the
      centrifugation of cells together with inoculated virus at 3,000 rpm for 2 h. This
      procedure forces viruses to attach to the cell surface, as revealed by
      quantitative estimation of attached virions by real-time PCR and also facilitated
      wt JHMV infection to MHVR-negative cells, but failed to do so for srr7. Virions
      of both wt and srr7 attached on MHVR-negative cells by spinoculation were
      facilitated for infection in the presence of a soluble form of MHVR that induces
      conformational changes of both wt and srr7. It was further revealed that wt JHMV
      S1, but not srr7, was released from the cell surface when S protein was expressed
      on cells. These observations support the hypothesis that attachment of the virion
      to MHVR-negative cells is a critical step and that a unique feature of wt JHMV S1
      to be released from S2 in a naturally occurring event is involved in an MHVR
      independent infection.

PMID- 16641282
TI  - Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in
      a minority of HIV-1-infected patients following treatment with the CCR5
      antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir.
AB  - Antagonists of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CCR5,
      are being developed as the first anti-HIV agents acting on a host cell target. We
      monitored the coreceptor tropism of circulating virus, screened at baseline for
      coreceptor tropism, in 64 HIV-1-infected patients who received maraviroc (MVC, UK
      427,857) as monotherapy for 10 days. Sixty-two patients harbored CCR5-tropic
      virus at baseline and had a posttreatment phenotype result. Circulating virus
      remained CCR5 tropic in 60/62 patients, 51 of whom experienced an HIV RNA
      reduction from baseline of >1 log(10) copies/ml, indicating that CXCR4-using
      variants were not rapidly selected despite CCR5-specific drug pressure. In two
      patients, viral load declined during treatment and CXCR4-using virus was detected
      at day 11. No pretreatment factor predicted the emergence of CXCR4-tropic virus
      during maraviroc therapy in these two patients. Phylogenetic analysis of envelope
      (Env) clones from pre- and posttreatment time points indicated that the CXCR4
      using variants probably emerged by outgrowth of a pretreatment CXCR4-using
      reservoir, rather than via coreceptor switch of a CCR5-tropic clone under
      selection pressure from maraviroc. Phylogenetic analysis was also performed on
      Env clones from a third patient harboring CXCR4-using virus prior to treatment.
      This patient was enrolled due to a sample labeling error. Although this patient
      experienced no overall reduction in viral load in response to treatment, the CCR5
      tropic components of the circulating virus did appear to be suppressed while
      receiving maraviroc as monotherapy. Importantly, in all three patients,
      circulating virus reverted to predominantly CCR5 tropic following cessation of
      maraviroc.

PMID- 16641283
TI  - Epigenetic regulation of varicella-zoster virus open reading frames 62 and 63 in
      latently infected human trigeminal ganglia.
AB  - Open reading frames (ORFs) 21, 29, 62, 63, and 66 of varicella-zoster virus (VZV)
      are transcribed during latency in human ganglia. ORF 63 is the most frequently
      expressed gene, and ORF 62 encodes a transcriptional activator. The mechanisms
      regulating the expression of these genes are not well understood, although
      analyses of other alphaherpesviruses indicate a role for chromatin in virus gene
      regulation during latent infection. Using chromatin immunoprecipitation (ChIP)
      assays to analyze the euchromatic state of ORFs 62 and 63 compared to the
      centromere from human chromosome 4 (heterochromatic) and the human glyceraldehyde
      3-phosphate dehydrogenase promoter (euchromatic), we show that the promoters of
      ORFs 62 and 63 are associated with the histone protein H3K9(Ac) and thus
      maintained in a euchromatic state during latency. Conversely, the promoters of
      ORF 36 (thymidine kinase) and ORF 14 (glycoprotein C), genes expressed during
      lytic but not latent infection, were not enriched in the fraction of latently
      infected ganglia that bound to anti-H3K9(Ac) antibody. A ChIP assay using
      productively infected MeWo cells revealed that VZV ORFs 62, 63, 36, and 14 are
      all euchromatic. Together, these data indicate that the expression of the two
      latency-related VZV genes, ORFs 62 and 63, is regulated epigenetically through
      chromatin structure.

PMID- 16641284
TI  - Adeno-associated virus type 2 increases proteosome-dependent degradation of
      p21WAF1 in a human papillomavirus type 31b-positive cervical carcinoma line.
AB  - Adeno-associated virus type 2 (AAV2) seropositivity is negatively correlated with
      the development of human papillomavirus (HPV)-associated cervical cancer. We have
      begun analysis of the molecular mechanisms underlying AAV2-mediated onco
      suppression through cell cycle regulation in HPV-infected keratinocytes isolated
      from a low-grade cervical lesion. AAV2 superinfection of HPV type 31b (HPV31b)
      positive cells at early times postinfection resulted in degradation of the cyclin
      dependent kinase (CDK) inhibitor p21(WAF1) protein in a proteosome-dependent
      manner. Downstream consequences of lowering p21(WAF1) levels included a
      proportional loss of cyclin E/CDK2 complexes bound to p21(WAF1). The loss of
      stable p21(WAF1)/cyclin E/CDK2 complexes coincided with an increase in CDK2
      associated kinase activity and cyclin E levels. Both events have the potential to
      enhance the G(1)/S transition point mediated by active cyclin E/CDK2 complexes.
      Concurrently, cyclin A and E2F levels were decreased, conditions reminiscent of
      delayed entrance into the S phase of the cell cycle. On the other hand, infection
      of primary human foreskin keratinocytes with AAV2 resulted in upregulation of
      p21(WAF1) protein levels, reminiscent of a block in G(1) phase progression. We
      propose that by down regulating p21(WAF1), AAV2 initiates cell cycle activities
      leading to enhanced G(1)/S phase-like conditions which may be favorable for AAV2
      specific functions and may lead to downstream interference with HPV-associated
      cervical cancer progression.

PMID- 16641285
TI  - Different domains of CD81 mediate distinct stages of hepatitis C virus
      pseudoparticle entry.
AB  - The CD81 tetraspanin was first identified as a hepatitis C virus (HCV) receptor
      by its ability to bind the soluble ectodomain of envelope glycoprotein E2 (sE2).
      More recently, it has been suggested that CD81 is necessary but not sufficient
      for HCV entry into target cells. Here we present further evidence that putative
      human hepatocyte-specific factors act in concert with CD81 to mediate sE2 binding
      and HCV pseudoparticle (HCVpp) entry. Moreover, we show that CD81-mediated HCVpp
      entry entails E2 binding to residues in the large extracellular loop as well as
      molecular events mediated by the transmembrane and intracellular domains of CD81.
      The concept that CD81 receptor function progresses in stages is further supported
      by our finding that anti-CD81 monoclonal antibodies inhibit HCVpp entry by
      different mechanisms. The half-life of CD81-HCVpp binding was determined to be
      approximately 17 min, and we propose that binding is followed by CD81
      oligomerization, partitioning into cholesterol-rich membrane domains, or other,
      lateral protein-protein interactions. This results in the formation of a receptor
      virus complex that undergoes endocytosis and pH-dependent membrane fusion.

PMID- 16641286
TI  - Mice develop effective but delayed protective immune responses when immunized as
      neonates either intranasally with nonliving VP6/LT(R192G) or orally with live
      rhesus rotavirus vaccine candidates.
AB  - Rotavirus vaccines are delivered early in life, when the immune system is
      immature. To determine the effects of immaturity on responses to candidate
      vaccines, neonatal (7 days old) and adult mice were immunized with single doses
      of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant
      LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus
      shedding following challenge with the murine rotavirus strain EDIM was
      determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were
      unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B
      cell (antibody) or CD4(+) CD8(+) T-cell (rotavirus-inducible, Th1 [gamma
      interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]
      producing spleen cells) responses. However, by 28 and 42 dpi, these mice were
      significantly (P >or= 0.003) protected and contained memory rotavirus-specific T
      cells but produced no rotavirus antibody. In contrast, adult mice were nearly
      fully protected by 10 dpi and contained both rotavirus immunoglobulin G and
      memory T cells. Neonates immunized orally with RRV were also less protected
      (P=0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus
      antibody. Both groups contained few rotavirus-specific memory T cells. Protection
      levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody
      levels. This report introduces a neonatal mouse model for active protection
      studies with rotavirus vaccines. It indicates that, with time, neonatal mice
      develop full protection after intranasal immunization with VP6/LT(R192G) or oral
      immunization with a live heterologous rotavirus and supports reports that
      protection depends on CD4(+) T cells or antibody, respectively.

PMID- 16641287
TI  - Phase I evaluation of intranasal trivalent inactivated influenza vaccine with
      nontoxigenic Escherichia coli enterotoxin and novel biovector as mucosal
      adjuvants, using adult volunteers.
AB  - Trivalent influenza virus A/Duck/Singapore (H5N3), A/Panama (H3N2), and
      B/Guandong vaccine preparations were used in a randomized, controlled, dose
      ranging phase I study. The vaccines were prepared from highly purified
      hemagglutinin and neuraminidase from influenza viruses propagated in embryonated
      chicken eggs and inactivated with formaldehyde. We assigned 100 participants to
      six vaccine groups, as follows. Three intranasally vaccinated groups received 7.5
      microg doses of hemagglutinin from each virus strain with either 3, 10, or 30
      microg of heat-labile Escherichia coli enterotoxin (LTK63) and 990 microg of a
      supramolecular biovector; one intranasally vaccinated group was given 7.5-microg
      doses of hemagglutinin with 30 microg of LTK63 without the biovector; and another
      intranasally vaccinated group received saline solution as a placebo. The final
      group received an intramuscular vaccine containing 15 microg hemagglutinin from
      each strain with MF59 adjuvant. The immunogenicity of two intranasal doses,
      delivered by syringe as drops into both nostrils with an interval of 1 week
      between, was compared with that of two inoculations by intramuscular delivery 3
      weeks apart. The intramuscular and intranasal vaccine formulations were both
      immunogenic but stimulated different limbs of the immune system. The largest
      increase in circulating antibodies occurred in response to intramuscular
      vaccination; the largest mucosal immunoglobulin A (IgA) response occurred in
      response to mucosal vaccination. Current licensing criteria for influenza
      vaccines in the European Union were satisfied by serum hemagglutination
      inhibition responses to A/Panama and B/Guandong hemagglutinins given with MF59
      adjuvant by injection and to B/Guandong hemagglutinin given intranasally with the
      highest dose of LTK63 and the biovector. Geometric mean serum antibody titers by
      hemagglutination inhibition and microneutralization were significantly higher for
      each virus strain at 3 and 6 weeks in recipients of the intramuscular vaccine
      than in recipients of the intranasal vaccine. The immunogenicity of the
      intranasally delivered experimental vaccine varied by influenza virus strain.
      Mucosal IgA responses to A/Duck/Singapore (H5N3), A/Panama (H3N2), and B/Guandong
      were highest in participants given 30 microg LTK63 with the biovector, occurring
      in 7/15 (47%; P=0.0103), 8/15 (53%; P=0.0362), and 14/15 (93%; P=0.0033)
      participants, respectively, compared to the placebo group. The addition of the
      biovector to the vaccine given with 30 microg LTK63 enhanced mucosal IgA
      responses to A/Duck/Singapore (H5N3) (P=0.0491) and B/Guandong (P=0.0028) but not
      to A/Panama (H3N2). All vaccines were well tolerated.

PMID- 16641288
TI  - The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase
      exhibits bidirectional phenotypic antagonism with thymidine analog mutations.
AB  - The K65R mutation in human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) is selected in vitro by many D-nucleoside analog RT inhibitors
      (NRTI) but has been rarely detected in treated patients. In recent clinical
      trials, the K65R mutation has emerged frequently in patients experiencing
      virologic failure on antiretroviral combinations that do not include 3'
      azidothymidine (AZT). The reason for this change is uncertain. To gain insight,
      we examined trends in the frequency of K65R in a large genotype database, the
      association of K65R with thymidine analog mutations (TAMs) and other NRTI
      mutations, and the viral susceptibility profile of HIV-1 with K65R alone and in
      combination with TAMs. Among >60,000 clinical samples submitted for genotype
      analysis that contained one or more NRTI resistance mutations, the frequency of
      K65R increased from 0.4% in 1998 to 3.6% in 2003. Among samples with K65R, a
      strong negative association was evident with the TAMs M41L, D67N, L210W, T215Y/F,
      and K219Q/E (P<0.005) but not with other NRTI mutations, including the Q151M
      complex. This suggested that K65R and TAMs are antagonistic. To test this
      possibility, we generated recombinant HIV-1 encoding K65R in two different TAM
      backgrounds: M41L/L210W/T215Y and D67N/K70R/T215F/K219Q. K65R reduced AZT
      resistance from >50-fold to <2.5-fold in both backgrounds. In addition, TAMs
      antagonized the phenotypic effect of K65R, reducing resistance to tenofovir,
      abacavir, 2',3'-dideoxycytidine, dideoxyinosine, and stavudine. In conclusion,
      K65R and TAMs exhibit bidirectional phenotypic antagonism. This antagonism likely
      explains the negative association of these mutations in genotype databases, the
      rare emergence of K65R with antiretroviral therapies that contain AZT, and its
      more frequent emergence with combinations that exclude AZT.

PMID- 16641289
TI  - Genome of crocodilepox virus.
AB  - Here, we present the genome sequence, with analysis, of a poxvirus infecting Nile
      crocodiles (Crocodylus niloticus) (crocodilepox virus; CRV). The genome is
      190,054 bp (62% G+C) and predicted to contain 173 genes encoding proteins of 53
      to 1,941 amino acids. The central genomic region contains genes conserved and
      generally colinear with those of other chordopoxviruses (ChPVs). CRV is distinct,
      as the terminal 33-kbp (left) and 13-kbp (right) genomic regions are largely CRV
      specific, containing 48 unique genes which lack similarity to other poxvirus
      genes. Notably, CRV also contains 14 unique genes which disrupt ChPV gene
      colinearity within the central genomic region, including 7 genes encoding GyrB
      like ATPase domains similar to those in cellular type IIA DNA topoisomerases,
      suggestive of novel ATP-dependent functions. The presence of 10 CRV proteins with
      similarity to components of cellular multisubunit E3 ubiquitin-protein ligase
      complexes, including 9 proteins containing F-box motifs and F-box-associated
      regions and a homologue of cellular anaphase-promoting complex subunit 11
      (Apc11), suggests that modification of host ubiquitination pathways may be
      significant for CRV-host cell interaction. CRV encodes a novel complement of
      proteins potentially involved in DNA replication, including a NAD(+)-dependent
      DNA ligase and a protein with similarity to both vaccinia virus F16L and
      prokaryotic serine site-specific resolvase-invertases. CRV lacks genes encoding
      proteins for nucleotide metabolism. CRV shares notable genomic similarities with
      molluscum contagiosum virus, including genes found only in these two viruses.
      Phylogenetic analysis indicates that CRV is quite distinct from other ChPVs,
      representing a new genus within the subfamily Chordopoxvirinae, and it lacks
      recognizable homologues of most ChPV genes involved in virulence and host range,
      including those involving interferon response, intracellular signaling, and host
      immune response modulation. These data reveal the unique nature of CRV and
      suggest mechanisms of virus-reptile host interaction.

PMID- 16641290
TI  - Effects of an opal termination codon preceding the nsP4 gene sequence in the
      O'Nyong-Nyong virus genome on Anopheles gambiae infectivity.
AB  - The genomic RNA of an alphavirus encodes four different nonstructural proteins,
      nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation
      terminates at an opal termination codon between nsP3 and nsP4. The polyprotein
      P1234 is produced when translational readthrough occurs or when the opal
      termination codon has been replaced by a sense codon in the alphavirus genome.
      Evolutionary pressures appear to have maintained genomic sequences encoding both
      a stop codon (opal) and an open reading frame (arginine) as a general feature of
      the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some
      point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts
      may determine predominance of a particular codon at this locus in the viral
      quasispecies. However, no systematic study has previously tested this hypothesis
      in whole animals. We report here the results of the first study to investigate in
      a natural mosquito host the functional significance of the opal stop codon in an
      alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series
      of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal,
      ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4
      nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a
      codon for the amino acid arginine at the corresponding position (39.8%). Although
      the frequency with which the opal virus disseminated from the mosquito midgut did
      not differ significantly from that of the arginine virus on days 8 and 10,
      dissemination did began earlier in mosquitoes infected with the opal virus.
      Although a clear fitness advantage is provided to ONNV by the presence of an opal
      codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA
      extracted from mosquito bodies and heads indicated codon usage at this position
      corresponded with that of the virus administered in the blood meal. These results
      suggest that while selection of ONNV variants is occurring, de novo mutation at
      the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken
      together, these results suggest that the primary fitness advantage provided to
      ONNV by the presence of an opal codon between nsP3 and nsP4 is related to
      mosquito infectivity.

PMID- 16641291
TI  - Molecular and biological characterization of deformed wing virus of honeybees
      (Apis mellifera L.).
AB  - Deformed wing virus (DWV) of honeybees (Apis mellifera) is closely associated
      with characteristic wing deformities, abdominal bloating, paralysis, and rapid
      mortality of emerging adult bees. The virus was purified from diseased insects,
      and its genome was cloned and sequenced. The genomic RNA of DWV is 10,140
      nucleotides in length and contains a single large open reading frame encoding a
      328-kDa polyprotein. The coding sequence is flanked by a 1,144-nucleotide 5'
      nontranslated leader sequence and a 317-nucleotide 3' nontranslated region,
      followed by a poly(A) tail. The three major structural proteins, VP1 (44 kDa),
      VP2 (32 kDa), and VP3 (28 kDa), were identified, and their genes were mapped to
      the N-terminal section of the polyprotein. The C-terminal part of the polyprotein
      contains sequence motifs typical of well-characterized picornavirus nonstructural
      proteins: an RNA helicase, a chymotrypsin-like 3C protease, and an RNA-dependent
      RNA polymerase. The genome organization, capsid morphology, and sequence
      comparison data indicate that DWV is a member of the recently established genus
      Iflavirus.

PMID- 16641292
TI  - Cellular splicing and transcription regulatory protein p32 represses adenovirus
      major late transcription and causes hyperphosphorylation of RNA polymerase II.
AB  - The cellular protein p32 is a multifunctional protein, which has been shown to
      interact with a large number of cellular and viral proteins and to regulate
      several important activities like transcription and RNA splicing. We have
      previously shown that p32 regulates RNA splicing by binding and inhibiting the
      essential SR protein ASF/SF2. To determine whether p32 also functions as a
      regulator of splicing in virus-infected cells, we constructed a recombinant
      adenovirus expressing p32 under the transcriptional control of an inducible
      promoter. Much to our surprise the results showed that p32 overexpression
      effectively blocked mRNA and protein expression from the adenovirus major late
      transcription unit (MLTU). Interestingly, the p32-mediated inhibition of MLTU
      transcription was accompanied by an approximately 4.5-fold increase in Ser 5
      phosphorylation and an approximately 2-fold increase in Ser 2 phosphorylation of
      the carboxy-terminal domain (CTD). Further, in p32-overexpressing cells the
      efficiency of RNA polymerase elongation was reduced approximately twofold,
      resulting in a decrease in the number of polymerase molecules that reached the
      end of the major late L1 transcription unit. We further show that p32 stimulates
      CTD phosphorylation in vitro. The inhibitory effect of p32 on MLTU transcription
      appears to require the CAAT box element in the major late promoter, suggesting
      that p32 may become tethered to the MLTU via an interaction with the CAAT box
      binding transcription factor.

PMID- 16641293
TI  - Human rhinovirus attenuates the type I interferon response by disrupting
      activation of interferon regulatory factor 3.
AB  - The type I interferon (IFN) response requires the coordinated activation of the
      latent transcription factors NF-kappaB, interferon regulatory factor 3 (IRF-3),
      and ATF-2, which in turn activate transcription from the IFN-beta promoter.
      Synthesis and subsequent secretion of IFN-beta activate the Jak/STAT signaling
      pathway, resulting in the transcriptional induction of the full spectrum of
      antiviral gene products. We utilized high-density microarrays to examine the
      transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells,
      with particular emphasis on the type I interferon response and production of IFN
      beta. We found that, although RV14 infection results in altered levels of a wide
      variety of host mRNAs, induction of IFN-beta mRNA or activation of the Jak/STAT
      pathway is not seen. Prior work has shown, and our results have confirmed, that
      NF-kappaB and ATF-2 are activated following infection. Since many viruses are
      known to target IRF-3 to inhibit the induction of IFN-beta mRNA, we analyzed the
      status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and
      phosphorylated in RV14-infected cells. Despite this apparent activation, very
      little homodimerization of IRF-3 was evident following infection. Similar results
      in A549 lung alveolar epithelial cells demonstrated the biological relevance of
      these findings to RV14 pathogenesis. In addition, prior infection of cells with
      RV14 prevented the induction of IFN-beta mRNA following treatment with double
      stranded RNA, indicating that RV14 encodes an activity that specifically inhibits
      this innate host defense pathway. Collectively, these results indicate that RV14
      infection inhibits the host type I interferon response by interfering with IRF-3
      activation.

PMID- 16641294
TI  - Alpha and lambda interferon together mediate suppression of CD4 T cells induced
      by respiratory syncytial virus.
AB  - The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell
      proliferation to itself and other antigens is poorly understood. We used monocyte
      derived dendritic cells (MDDC) and CD4 T cells and measured [(3)H]thymidine
      incorporation to determine the factors responsible for RSV-induced T-cell
      suppression. These two cell types were sufficient for RSV-induced suppression of
      T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin
      B. Suppressive activity was transferable with supernatants from RSV-infected MDDC
      and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants
      from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions,
      contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda
      (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal
      antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with
      MAb against either of its receptor chains, IFN-lambdaR1 (interleukin 28R [IL
      28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors
      together markedly reduced or completely blocked the RSV-induced suppression of
      CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may
      guide vaccine design and provide insight into previously uncharacterized human T
      cell responses and activities of interferons.

PMID- 16641295
TI  - The unique IR2 protein of equine herpesvirus 1 negatively regulates viral gene
      expression.
AB  - The IR2 protein (IR2P) is a truncated form of the immediate-early protein (IEP)
      lacking the essential acidic transcriptional activation domain (TAD) and serine
      rich tract and yet retaining binding domains for DNA and TFIIB and nuclear
      localization signal (NLS). Analysis of the IR2 promoter indicated that the IR2
      promoter was upregulated by the EICP0P. The IR2P was first detected in the
      nucleus at 5 h postinfection in equine herpesvirus 1 (EHV-1)-infected HeLa and
      equine NBL6 cells. Transient-transfection assays revealed that (i) the IR2P by
      itself downregulated EHV-1 early promoters (EICP0, TK, EICP22, and EICP27) in a
      dose-dependent manner; (ii) the IR2P abrogated the IEP and the EICP27P (UL5)
      mediated transactivation of viral promoters in a dose-dependent manner; and (iii)
      the IR2P, like the IEP itself, also downregulated the IE promoter, indicating
      that the IEP TAD is not necessary to downregulate the IE promoter. In vitro
      interaction assays revealed that the IR2P interacts with TATA box-binding protein
      (TBP). The essential domain(s) of the IR2P that mediate negative regulation were
      mapped to amino acid residues 1 to 706, indicating that the DNA-binding domain
      and the NLS of the IR2P may be important for the downregulation. In transient
      transfection and virus growth assays, the IR2P reduced EHV-1 production by 23
      fold compared to virus titers achieved in cells transfected with the empty
      vector. Overall, these studies suggest that the IR2P downregulates viral gene
      expression by acting as a dominant-negative protein that blocks IEP-binding to
      viral promoters and/or squelching the limited supplies of TFIIB and TBP.

PMID- 16641296
TI  - X-ray crystallographic structure of the Norwalk virus protease at 1.5-A
      resolution.
AB  - Norwalk virus (NV), a member of the Caliciviridae family, is the major cause of
      acute, epidemic, viral gastroenteritis. The NV genome is a positive sense, single
      stranded RNA that encodes three open reading frames (ORFs). The first ORF
      produces a polyprotein that is processed by the viral cysteine protease into six
      nonstructural proteins. We have determined the structure of the NV protease to
      1.5 and 2.2 A from crystals grown in the absence or presence, respectively, of
      the protease inhibitor AEBSF [4-(2-aminoethyl)-benzenesulfonyl fluoride]. The
      protease, which crystallizes as a stable dimer, exhibits a two-domain structure
      similar to those of other viral cysteine proteases with a catalytic triad
      composed of His 30, Glu 54, and Cys 139. The native structure of the protease
      reveals strong hydrogen bond interactions between His 30 and Glu 54, in the
      favorable syn configuration, indicating a role of Glu 54 during proteolysis.
      Mutation of this residue to Ala abolished the protease activity, in a fluorogenic
      peptide substrate assay, further substantiating the role of Glu 54 during
      proteolysis. These observations contrast with the suggestion, from a previous
      study of another norovirus protease, that this residue may not have a prominent
      role in proteolysis (K. Nakamura, Y. Someya, T. Kumasaka, G. Ueno, M. Yamamoto,
      T. Sato, N. Takeda, T. Miyamura, and N. Tanaka, J. Virol. 79:13685-13693, 2005).
      In the structure from crystals grown in the presence of AEBSF, Glu 54 undergoes a
      conformational change leading to disruption of the hydrogen bond interactions
      with His 30. Since AEBSF was not apparent in the electron density map, it is
      possible that these conformational changes are due to subtle changes in pH caused
      by its addition during crystallization.

PMID- 16641297
TI  - Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses
      but not in detectable amounts by negative-strand RNA viruses.
AB  - Double-stranded RNA (dsRNA) longer than 30 bp is a key activator of the innate
      immune response against viral infections. It is widely assumed that the
      generation of dsRNA during genome replication is a trait shared by all viruses.
      However, to our knowledge, no study exists in which the production of dsRNA by
      different viruses is systematically investigated. Here, we investigated the
      presence and localization of dsRNA in cells infected with a range of viruses,
      employing a dsRNA-specific antibody for immunofluorescence analysis. Our data
      revealed that, as predicted, significant amounts of dsRNA can be detected for
      viruses with a genome consisting of positive-strand RNA, dsRNA, or DNA.
      Surprisingly, however, no dsRNA signals were detected for negative-strand RNA
      viruses. Thus, dsRNA is indeed a general feature of most virus groups, but
      negative-strand RNA viruses appear to be an exception to that rule.

PMID- 16641298
TI  - The ORF3 protein of porcine circovirus type 2 is involved in viral pathogenesis
      in vivo.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of an emerging
      swine disease, postweaning multisystemic wasting syndrome. We previously showed
      that a novel identified protein, ORF3, was not essential for PCV2 replication in
      cultured PK15 cells and played a major role in virus-induced apoptosis. To
      evaluate the role of the ORF3 protein in viral pathogenesis in vivo, we
      inoculated 8-week-old BALB/c mice that have been developed for PCV2 replication
      with ORF3-deficient mutant PCV2 (mPCV2). By 42 days postinoculation, all of the
      mice inoculated with the mPCV2, as well as with wild-type PCV2 (wPCV2), had
      seroconverted to PCV2 capsid antibody, and the mutant induced levels of PCV2
      antibodies that were higher than those of the wPCV2. The PCV2 genomic copy
      numbers in serum were significantly higher (P<0.05) in the wPCV2-inoculated mice
      than in mice inoculated with the mPCV2. Also, the wPCV2 caused microscopic
      lesions characterized by lymphocyte depletion with histiocytic infiltration of
      lymphoid organs, but the mutant virus failed to induce any obvious pathological
      lesions. In situ hybridization and immunohistochemical analyses also showed that
      larger amounts of viral DNA and antigens were detected in the lymph nodes of the
      wPCV2-inoculated than mPCV2-inoculated mice. Furthermore, animals of the wPCV2
      inoculated group showed significant downshifts of CD8(+) T-cell subsets of
      peripheral blood lymphocytes compared to the control mice (P<0.05) at various
      time points postinoculation. Also, the proportions of the CD4(+) and CD4(+)
      CD8(+) cells were significantly reduced in wPCV2-inoculated mice at some time
      points postinoculation. In contrast, there are some reductions in the proportions
      of these subsets in the mutant virus-inoculated mice, but the proportions do not
      decrease significantly. Taken together, these results demonstrate that the ORF3
      protein is also dispensable for viral replication in vivo and that it plays an
      important role in viral pathogenesis.

PMID- 16641299
TI  - The high-frequency major histocompatibility complex class I allele Mamu-B*17 is
      associated with control of simian immunodeficiency virus SIVmac239 replication.
AB  - Particular HLA alleles are associated with reduced human immunodeficiency virus
      replication. It has been difficult, however, to characterize the immune
      correlates of viral control. An analysis of the influence of major
      histocompatibility complex class I alleles on viral control in 181 simian
      immunodeficiency virus SIVmac239-infected rhesus macaques revealed that Mamu
      B(*)17 was associated with a 26-fold reduction in plasma virus concentrations
      (P<0.001). Mamu-B(*)17 was also enriched in a group of animals that controlled
      viral replication by 1,000-fold [corrected] Even after accounting for this group,
      Mamu-B(*)17 was associated with an eightfold reduction in plasma virus
      concentrations (P<0.001). Mamu-B(*)17-positive macaques could, therefore,
      facilitate our understanding of the correlates of viral control.

PMID- 16641300
TI  - The Epstein-Barr virus BMRF1 gene is essential for lytic virus replication.
AB  - The Epstein-Barr virus (EBV) BMRF1 protein is a DNA polymerase processivity
      factor. We have deleted the BMRF1 open reading frame from the EBV genome and
      assessed the DeltaBMRF1 EBV phenotype. DeltaBMRF1 viruses were replication
      deficient, but the wild-type phenotype could be restored by BMRF1 trans
      complementation. The replication-deficient phenotype included impaired lytic DNA
      replication and late protein expression. DeltaBMRF1 and wild-type viruses were
      undistinguishable in terms of their ability to transform primary B cells. Our
      results provide genetic evidence that BMRF1 is essential for lytic replication of
      the EBV genome.

PMID- 16641301
TI  - Identification and characterization of novel adeno-associated virus isolates in
      ATCC virus stocks.
AB  - Adeno-associated viruses (AAVs) depend on a helper virus for efficient
      replication. To identify novel AAV isolates, we screened a diverse set of virus
      isolates for the presence of AAV DNA. AAVs found in 10 simian adenovirus isolates
      showed greater than 96% homology to AAV1 and AAV6 but had distinct biological
      properties. Two representatives of this group, AAV(VR-195) and AAV(VR-355), were
      studied in more detail. While the novel AAVs had high sequence homologies and
      required sialic acid for cell binding and transduction, differences were observed
      in lectin competition, resulting in distinct tropisms in human cancer cell lines.

PMID- 16641302
TI  - Chaperone-mediated in vitro disassembly of polyoma- and papillomaviruses.
AB  - Hsp70 chaperones play a role in polyoma- and papillomavirus assembly, as
      evidenced by their interaction in vivo with polyomavirus capsid proteins at late
      times after virus infection and by their ability to assemble viral capsomeres
      into capsids in vitro. We studied whether Hsp70 chaperones might also participate
      in the uncoating reaction. In vivo, Hsp70 co-immunoprecipitated with polyomavirus
      virion VP1 at 3 h after infection of mouse cells. In vitro, prokaryotic and
      eukaryotic Hsp70 chaperones efficiently disassembled polyoma- and papillomavirus
      like particles and virions in energy-dependent reactions. These observations
      support a role for cell chaperones in the disassembly of these viruses.

PMID- 16641303
TI  - Isolation and genetic characterization of new reassortant H3N1 swine influenza
      virus from pigs in the midwestern United States.
AB  - Since the introduction of H3N2 swine influenza viruses (SIVs) into U.S. swine in
      1998, H1N2 and H1N1 reassortant viruses have emerged from reassortment between
      classical H1N1 and H3N2 viruses. In 2004, a new reassortant H3N1 virus
      (A/Swine/Minnesota/00395/2004) was identified from coughing pigs. Phylogenetic
      analyses revealed a hemagglutinin segment similar to those of contemporary
      cluster III H3N2 SIVs and a neuraminidase sequence of contemporary H1N1 origin.
      The internal genes were of swine, human, and avian influenza virus origin,
      similar to those of contemporary U.S. cluster III H3N2 SIVs. The recovery of H3N1
      is further evidence of reassortment among SIVs and justifies continuous
      surveillance.

PMID- 16641304
TI  - Immunoglobulin GM and KM allotypes and prevalence of anti-LKM1 autoantibodies in
      patients with hepatitis C virus infection.
AB  - GM and KM allotypes-genetic markers of immunoglobulin (Ig) gamma and kappa
      chains, respectively-are associated with humoral immunity to several infection-
      and autoimmunity-related epitopes. We hypothesized that GM and KM allotypes
      contribute to the generation of autoantibodies to liver/kidney microsomal antigen
      1 (LKM1) in hepatitis C virus (HCV)-infected persons. To test this hypothesis, we
      characterized 129 persons with persistent HCV infection for several GM and KM
      markers and for anti-LKM1 antibodies. The heterozygous GM 1,3,17 23 5,13,21
      phenotype was significantly associated with the prevalence of anti-LKM1
      antibodies (odds ratio, 5.13; P=0.002), suggesting its involvement in this
      autoimmune phenomenon in HCV infection.

PMID- 16641305
TI  - Tracking the epidemiology of human genes in the literature: the HuGE Published
      Literature database.
AB  - Completion of the human genome sequence has inspired a new wave of epidemiologic
      studies on the prevalence of gene variants and their associations with diseases
      in human populations. In 2001, the Human Genome Epidemiology (HuGE) Network
      launched the HuGE Published Literature database (HuGE Pub Lit), a searchable,
      online knowledge base of published, population-based epidemiologic studies of
      human genes. The database contains links to PubMed articles and can be searched
      by gene, disease, interacting factor, type of study design or analysis, or any
      combination of terms in these categories. The search output contains a link to
      each identified article, along with a table summarizing key features of the
      reported study. As of September 6, 2005, some 17,665 articles were indexed in the
      database. Most described gene-disease associations (86%); fewer evaluated gene
      gene or gene-environment interactions (17%), the prevalence of gene variants
      (10%), or genetic tests (3%). Although not comprehensive, this database is a
      unique tool for epidemiologic researchers and others concerned with the role of
      genetic variation in population health. Here, the authors provide an overview of
      the database and its characteristics and uses.

PMID- 16641306
TI  - Re: "combined postmenopausal hormone therapy and cardiovascular disease: toward
      resolving the discrepancy between observational studies and the women's health
      initiative clinical trial".

PMID- 16641307
TI  - Accounting for independent nondifferential misclassification does not increase
      certainty that an observed association is in the correct direction.
AB  - Researchers sometimes argue that their exposure-measurement errors are
      independent of other errors and are nondifferential with respect to disease,
      resulting in estimation bias toward the null. Among well-known problems with such
      arguments are that independence and nondifferentiality are harder to satisfy than
      ordinarily appreciated (e.g., because of correlation of errors in questionnaire
      items, and because of uncontrolled covariate effects on error rates); small
      violations of independence or nondifferentiality may lead to bias away from the
      null; and, if exposure is polytomous, the bias produced by independent
      nondifferential error is not always toward the null. The authors add to this list
      by showing that, in a 2 x 2 table (for which independent nondifferential error
      produces bias toward the null), accounting for independent nondifferential error
      does not reduce the p value even though it increases the point estimate. Thus,
      such accounting should not increase certainty that an association is present.

PMID- 16641308
TI  - Which patients' factors predict the rate of growth of Mycobacterium tuberculosis
      clusters in an urban community?
AB  - Factors influencing tuberculosis cluster growth are poorly understood. The
      authors examined clusters of two or more culture-confirmed Mycobacterium
      tuberculosis cases between January 1, 2001, and December 31, 2003, that had
      insertion sequence 6110 (IS6110) restriction fragment length polymorphism and
      spoligotype patterns identical to those of another study case. Genotypes first
      seen in New York, New York, before or during 1993 were considered historical;
      recent strains were those first seen after 1993. The authors examined the effect
      of the combined characteristics of infectiousness of the first two cases in a
      cluster on the rate of cluster growth. Genotyping was performed for 2,408 (91.8%)
      of the 2,623 tuberculosis cases diagnosed; 873 cases were in 212 clusters. Thirty
      one clusters had historical strains, 153 were recent, and 28 were of unknown
      period. Patients' infectiousness was not associated with the rate of cluster
      growth among historical strain clusters. Among recent strain clusters,
      infectiousness of both of the initial cases was associated with a higher rate of
      cluster growth compared with clusters in which neither initial case was
      infectious, upon adjustment for male sex (rate ratio = 2.62, 95% confidence
      interval: 1.19, 5.78). The rate of genotype cluster growth should be monitored
      regardless of how long the strain has been present in the community. However,
      infectiousness in the first two cases may be useful to prioritize genotype
      cluster investigations.

PMID- 16641309
TI  - Myeloperoxidase polymorphism and cognitive decline in older adults in the Health,
      Aging, and Body Composition Study.
AB  - Myeloperoxidase, an antimicrobial enzyme, produces oxidative free radicals.
      Rarely found in normal brain tissue, myeloperoxidase has been detected in
      microglia associated with Alzheimer's disease plaques. The authors examined a G
      463A polymorphism in the promoter region of the myeloperoxidase gene (MPO) to
      determine the relation of MPO variants to cognitive decline over 4 years in a
      cohort of adults, aged 70-79 years at baseline (1997-1998), recruited from
      Memphis, Tennessee, and Pittsburgh, Pennsylvania, into the Health, Aging, and
      Body Composition Study. In this sample, 8% of the participants had the AA, 36.9%
      the AG, and 55.2% the GG genotype of MPO. The frequency of AA and AG genotypes
      was higher in Blacks than Whites (11.2% vs. 5.9%, and 44.1% vs. 32.9%,
      respectively). Multivariate logistic regression analyses showed that, for
      participants with the MPO AA genotype, cognitive decline was 1.58 (95% confidence
      interval: 1.07, 2.35) times more likely than for participants with the AG
      genotype and 1.96 (95% confidence interval: 1.33, 2.88) times more likely than
      for those with the GG genotype. Interactions between MPO and race, sex, or the
      apolipoprotein gene were not significant. In this sample, MPO AA, associated with
      decreased production of myeloperoxidase, was found to be a risk factor for
      cognitive decline.

PMID- 16641310
TI  - Caffeine metabolites in umbilical cord blood, cytochrome P-450 1A2 activity, and
      intrauterine growth restriction.
AB  - Studies investigating antenatal caffeine consumption and reproductive outcomes
      show conflicting results, and most studies have used maternal self-reported
      caffeine consumption to estimate fetal exposure. This study (n=1,606) was
      specifically designed to test the association of caffeine and its primary
      metabolites in umbilical cord blood with intrauterine growth restriction (IUGR).
      Pregnant women were recruited from 56 obstetric practices and 15 clinics
      affiliated with six hospitals in Connecticut and Massachusetts between September
      1996 and January 2000. In an adjusted model including caffeine only, levels in
      all quartiles were associated with reduced risk of IUGR. In adjusted analyses
      including paraxanthine and caffeine, serum paraxanthine levels in the highest
      quartile were associated with increased risk of IUGR (adjusted odds ratio=3.29,
      95% confidence interval: 1.17, 9.22); caffeine remained protective. These
      conflicting findings suggest that cytochrome P-450 1A2 (CYP1A2) metabolic
      activity may be associated with IUGR, so the ratio of paraxanthine to caffeine
      was then modeled. The likelihood of IUGR increased 21% for every one standard
      deviation change in the ratio (adjusted odds ratio=1.21, 95% confidence interval:
      1.07, 1.37), suggesting that CYP1A2 activity, and not the absolute levels of
      paraxanthine, influences fetal growth. No associations were observed between
      caffeine or any metabolites and preterm delivery.

PMID- 16641311
TI  - Association of body mass index and weight change with all-cause mortality in the
      elderly.
AB  - The authors explored the relation of body mass index (BMI; weight (kg)/height
      (m)(2)) and weight change to all-cause mortality in the elderly, using data from
      a large, population-based California cohort study, the Leisure World Cohort
      Study. They estimated relative risks of mortality associated with self-reported
      BMI at study entry, BMI at age 21 years, and weight change between age 21 and
      study entry. Participants were categorized as underweight (BMI <18.5), normal
      weight (BMI 18.5-24.9), overweight (BMI 25-29.9), or obese (BMI >or=30). Of
      13,451 participants aged 73 years (on average) at study entry (1981-1985), 11,203
      died during 23 years of follow-up (1981-2004). Relative to normal weight, being
      underweight (relative risk (RR) = 1.51, 95% confidence interval (CI): 1.38, 1.65)
      or obese (RR = 1.25, 95% CI: 1.13, 1.38) at study entry was associated with
      increased mortality. People who were either overweight or obese at age 21 also
      had increased mortality (RR = 1.17, 95% CI: 1.09, 1.25). Participants who lost
      weight between age 21 and study entry had increased mortality regardless of their
      BMI category at age 21. Obesity was significantly associated with increased
      mortality only among persons under age 75 years and among never or past smokers.
      This study highlights the influence on older-age mortality risk of being
      overweight or obese in young adulthood and underweight or obese in later life.

PMID- 16641312
TI  - Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from
      the scorpion Odonthobuthus doriae.
AB  - Voltage-gated sodium channels are essential for the propagation of action
      potentials in nociceptive neurons. Nav1.7 is found in peripheral sensory and
      sympathetic neurons and involved in short-term and inflammatory pain. Nav1.8 and
      Nav1.3 are major players in nociception and neuropathic pain, respectively. In
      our effort to identify isoform-specific and high-affinity ligands for these
      channels, we investigated the effects of OD1, a scorpion toxin isolated from the
      venom of the scorpion Odonthobuthus doriae. Nav1.3, Nav1.7, and Nav1.8 channels
      were coexpressed with beta1-subunits in Xenopus laevis oocytes. Na+ currents were
      recorded with the two-electrode voltage-clamp technique. OD1 modulates Nav1.7 at
      low nanomolar concentrations: 1) fast inactivation is dramatically impaired, with
      an EC50 value of 4.5 nM; 2) OD1 substantially increases the peak current at all
      voltages; and 3) OD1 induces a substantial persistent current. Nav1.8 was not
      affected by concentrations up to 2 microM, whereas Nav1.3 was sensitive only to
      concentrations higher than 100 nM. OD1 impairs the inactivation process of Nav1.3
      with an EC50 value of 1127 nM. Finally, the effects of OD1 were compared with a
      classic alpha-toxin, AahII from Androctonus australis Hector and a classic alpha
      like toxin, BmK M1 from Buthus martensii Karsch. At a concentration of 50 nM,
      both toxins affected Nav1.7. Nav1.3 was sensitive to AahII but not to BmK M1,
      whereas Nav1.8 was affected by neither toxin. In conclusion, the present study
      shows that the scorpion toxin OD1 is a potent modulator of Nav1.7, with a unique
      selectivity pattern.

PMID- 16641313
TI  - Analysis of G protein betagamma dimer formation in live cells using multicolor
      bimolecular fluorescence complementation demonstrates preferences of beta1 for
      particular gamma subunits.
AB  - The specificity of G protein betagamma signaling demonstrated by in vivo
      knockouts is greater than expected based on in vitro assays of betagamma
      function. In this study, we investigated the basis for this discrepancy by
      comparing the abilities of seven beta1gamma complexes containing gamma1, gamma2,
      gamma5, gamma7, gamma10, gamma11, or gamma12 to interact with alphas and of these
      gamma subunits to compete for interaction with beta1 in live human embryonic
      kidney (HEK) 293 cells. betagamma complexes were imaged using bimolecular
      fluorescence complementation, in which fluorescence is produced by two
      nonfluorescent fragments (N and C) of cyan fluorescent protein (CFP) or yellow
      fluorescent protein (YFP) when brought together by proteins fused to each
      fragment. Plasma membrane targeting of alphas-CFP varied inversely with its
      expression level, and the abilities of YFP-N-beta1YFP-C-gamma complexes to
      increase this targeting varied by 2-fold or less. However, there were larger
      differences in the abilities of the CFP-N-gamma subunits to compete for
      association with CFP-C-beta1. When the intensities of coexpressed CFP-C-beta1CFP
      N-gamma (cyan) and CFP-C-beta1YFP-N-gamma2 (yellow) complexes were compared under
      conditions in which CFP-C-beta1 was limiting, the CFP-N-gamma subunits exhibited
      a 4.5-fold range in their abilities to compete with YFP-N-gamma2 for association
      with CFP-C-beta1. CFP-N-gamma12 and CFP-N-gamma1 were the strongest and weakest
      competitors, respectively. Taken together with previous demonstrations of a role
      for betagamma in the specificity of receptor signaling, these results suggest
      that differences in the association preferences of coexpressed beta and gamma
      subunits for each other can determine which complexes predominate and participate
      in signaling pathways in intact cells.

PMID- 16641314
TI  - Potentiation of acetylcholine receptors by divalent cations.
AB  - Divalent cations promote activation of several nicotinic acetylcholine receptor
      (AChR) subtypes, presumably by lowering the energetic barrier between open and
      closed conformations. In wild-type alpha7 AChRs, binding of calcium to a
      particular part of the extracellular domain is required for potentiating
      activation. McLaughlin et al. (p. 16) tested the hypothesis that movements
      involved in agonist activation and calcium modulation involve a nearby beta sheet
      by linking strands within this sheet through disulfide bonds formed by replacing
      adjacent amino acids with cysteines to alter its mobility. These studies are
      helping to reveal how movements initiated by agonist binding to ACh binding sites
      are propagated through the extracellular domain of AChRs to regulate opening of
      the cation channel through the membrane.

PMID- 16641315
TI  - Allosteric interactions with muscarinic acetylcholine receptors: complex role of
      the conserved tryptophan M2422Trp in a critical cluster of amino acids for
      baseline affinity, subtype selectivity, and cooperativity.
AB  - In general, the M2 subtype of muscarinic acetylcholine receptors has the highest
      sensitivity for allosteric modulators and the M5 subtype the lowest. The M2/M5
      selectivity of some structurally diverse allosteric agents is known to be
      completely explained by M2 177Tyr and M2 423Thr in receptors whose orthosteric
      site is occupied by the conventional ligand N-methylscopolamine (NMS). This study
      explored the role of the conserved M2 422Trp and the adjacent M2 423Thr in the
      binding of alkane-bisammonio type modulators, gallamine, and diallylcaracurine V.
      Experiments were performed with human M2 or M5 receptors or mutants thereof. It
      was found that M2 422Trp and M2 423Thr independently influenced allosteric agent
      binding. The presence of M2 423Thr may enhance the affinity of binding, depending
      on the allosteric agent, either directly or indirectly (by avoiding sterical
      hindrance through its M5 counterpart 478His). Replacement of M2 422Trp and of the
      corresponding M5 477Trp by alanine revealed a pronounced contribution of these
      epitopes to subtype independent baseline affinity in NMS-bound and NMS-free
      receptors for all agents except diallylcaracurine V. In a few instances, this
      tryptophan also influenced cooperativity and subtype selectivity. Docking
      simulations using a three-dimensional M2 receptor model revealed that the
      aromatic rings of M2 177Tyr and M2 422Trp, in a concerted action, might fix one
      of the aromatic moieties of alkane-bisammonio compounds between them. Thus, M2
      422Trp and the spatially adjacent M2 177Tyr, as well as M2 423Thr, form a cluster
      of amino acids within the allosteric binding cleft that is pivotal for both M2/M5
      subtype selectivity and baseline affinity of allosteric agents.

PMID- 16641316
TI  - Pregabalin reduces the release of synaptic vesicles from cultured hippocampal
      neurons.
AB  - Pregabalin [S-[+]-3-isobutylGABA or (S)-3-(aminomethyl)-5-methylhexanoic acid,
      Lyrica] is an anticonvulsant and analgesic medication that is both structurally
      and pharmacologically related to gabapentin (Neurontin; Pfizer Inc., New York,
      NY). Previous studies have shown that pregabalin reduces the release of
      neurotransmitters in several in vitro preparations, although the molecular
      details of these effects are less clear. The present study was performed using
      living cultured rat hippocampal neurons with the synaptic vesicle fluorescent dye
      probe FM4-64 to determine details of the action of pregabalin to reduce
      neurotransmitter release. Our results indicate that pregabalin treatment, at
      concentrations that are therapeutically relevant, slightly but significantly
      reduces the emptying of neurotransmitter vesicles from presynaptic sites in
      living neurons. Dye release is reduced in both glutamic acid decarboxylase (GAD)
      immunoreactive and GAD-negative (presumed glutamatergic) synaptic terminals.
      Furthermore, both calcium-dependent release and hyperosmotic (calcium
      independent) dye release are reduced by pregabalin. The effects of pregabalin on
      dye release are masked in the presence of l-isoleucine, consistent with the fact
      that both of these compounds have a high binding affinity to the calcium channel
      alpha(2)-delta protein. The effect of pregabalin is not apparent in the presence
      of an N-methyl-d-aspartate (NMDA) antagonist [D(-)-2-amino-5-phosphonopentanoic
      acid], suggesting that pregabalin action depends on NMDA receptor activation.
      Finally, the action of pregabalin on dye release is most apparent before and
      early during a train of electrical stimuli when vesicle release preferentially
      involves the readily releasable pool.

PMID- 16641317
TI  - Predictive modelling of topology and loop variations in dimeric DNA quadruplex
      structures.
AB  - We have used a combination of simulated annealing (SA), molecular dynamics (MD)
      and locally enhanced sampling (LES) methods in order to predict the favourable
      topologies and loop conformations of dimeric DNA quadruplexes with T2 or T3
      loops. This follows on from our previous MD simulation studies on the influence
      of loop lengths on the topology of intramolecular quadruplex structures [P. Hazel
      et al. (2004) J. Am. Chem. Soc., 126, 16 405-16 415], which provided results
      consistent with biophysical data. The recent crystal structures of d(G4T3G4)2 and
      d(G4BrUT2G4) (P. Hazel et al. (2006) J. Am. Chem. Soc., in press) and the NMR
      determined topology of d(TG4T2G4T)2 [A.T. Phan et al. (2004) J. Mol. Biol., 338,
      93-102] have been used in the present study for comparison with simulation
      results. These together with MM-PBSA free-energy calculations indicate that
      lateral T3 loops are favoured over diagonal loops, in accordance with the
      experimental structures; however, distinct loop conformations have been predicted
      to be favoured compared to those found experimentally. Several lateral and
      diagonal loop conformations have been found to be similar in energy. The
      simulations suggest an explanation for the distinct patterns of observed dimer
      topology for sequences with T3 and T2 loops, which depend on the loop lengths,
      rather than only on G-quartet stability.

PMID- 16641318
TI  - Specific RNA binding to ordered phospholipid bilayers.
AB  - We have studied RNA binding to vesicles bounded by ordered and disordered
      phospholipid membranes. A positive correlation exists between bilayer order and
      RNA affinity. In particular, structure-dependent RNA binding appears for rafted
      (liquid-ordered) domains in sphingomyelin-cholesterol-1,2-dioleoyl-sn-glycero-3
      phosphocholine vesicles. Binding to more highly ordered gel phase membranes is
      stronger, but much less RNA structure-dependent. All modes of RNA-membrane
      association seem to be electrostatic and headgroup directed. Fluorometry on 1,2
      dimyristoyl-sn-glycero-3-phosphocholine liposomes indicates that bound RNA
      broadens the gel-fluid melting transition, and reduces lipid headgroup order, as
      detected via fluorometric measurement of intramembrane electric fields. RNA
      preference for rafted lipid was visualized and confirmed using multiple
      fluorophores that allow fluorescence and fluorescence resonance energy transfer
      microscopy on RNA molecules closely associated with ordered lipid patches within
      giant vesicles. Accordingly, both RNA structure and membrane order could modulate
      biological RNA-membrane interactions.

PMID- 16641319
TI  - Prediction of yeast protein-protein interaction network: insights from the Gene
      Ontology and annotations.
AB  - A map of protein-protein interactions provides valuable insight into the cellular
      function and machinery of a proteome. By measuring the similarity between two
      Gene Ontology (GO) terms with a relative specificity semantic relation, here, we
      proposed a new method of reconstructing a yeast protein-protein interaction map
      that is solely based on the GO annotations. The method was validated using high
      quality interaction datasets for its effectiveness. Based on a Z-score analysis,
      a positive dataset and a negative dataset for protein-protein interactions were
      derived. Moreover, a gold standard positive (GSP) dataset with the highest level
      of confidence that covered 78% of the high-quality interaction dataset and a gold
      standard negative (GSN) dataset with the lowest level of confidence were derived.
      In addition, we assessed four high-throughput experimental interaction datasets
      using the positives and the negatives as well as GSPs and GSNs. Our predicted
      network reconstructed from GSPs consists of 40,753 interactions among 2259
      proteins, and forms 16 connected components. We mapped all of the MIPS complexes
      except for homodimers onto the predicted network. As a result, approximately 35%
      of complexes were identified interconnected. For seven complexes, we also
      identified some nonmember proteins that may be functionally related to the
      complexes concerned. This analysis is expected to provide a new approach for
      predicting the protein-protein interaction maps from other completely sequenced
      genomes with high-quality GO-based annotations.

PMID- 16641320
TI  - Inhibition of beta-defensin gene expression in airway epithelial cells by low
      doses of residual oil fly ash is mediated by vanadium.
AB  - Poor ambient air quality is associated with increased morbidity and mortality,
      including respiratory infections. However, its effects on various host-defense
      mechanisms are poorly understood. This study utilized an in vitro model to study
      the effect of particulate matter (PM(2.5)) on one antimicrobial mechanism of host
      defense in the airway, beta-defensin-2 and its bovine homologue, tracheal
      antimicrobial peptide (TAP) induction in response to lipopolysaccharide (LPS) and
      IL-1beta. Our model utilized cultured primary bovine tracheal epithelial (BTE)
      cells and the human alveolar type II epithelial cell line, A549, treated with 0
      20 microg/cm(2) residual oil fly ash (ROFA) for 6 h. The cells were then washed
      and stimulated for 18 h with 100 ng/ml LPS or for 6 h with 100 ng/ml IL-1beta.
      ROFA inhibited the LPS-induced increase in TAP mRNA and protein without inducing
      significant cytotoxicity. As little as 2.5 microg/cm(2) of ROFA inhibited LPS
      induced TAP gene expression by 30%. The inhibitory activity was associated with
      the soluble fraction and not the washed particle. The activity in the leachate
      was attributed to vanadium, but not nickel or iron. SiO(2) and TiO(2) were
      utilized as controls and did not inhibit LPS induction of TAP gene expression in
      BTE. ROFA also inhibited the increase of IL-1beta-induced human beta-defensin-2,
      a homologue of TAP, in A549 cells. The results show that ROFA, V(2)O(5), and
      VOSO(4) inhibit the ability of airway epithelial cells to respond to inflammatory
      stimuli at low, physiologically relevant doses and suggest that exposure to these
      agents could result in an impairment of defense against airborne pathogens.

PMID- 16641321
TI  - Ochratoxin A: apoptosis and aberrant exit from mitosis due to perturbation of
      microtubule dynamics?
AB  - Ochratoxin A (OTA) is a potent nephrotoxin and causes high incidences of renal
      tumors in rodents. The molecular events leading to tumor formation by OTA are not
      well defined. Early pathological changes observed in kidneys of rats treated with
      OTA in vivo include frequent mitotic and abnormally enlarged cells, detachment of
      tubule cells, and apoptosis within the S3 segment of the proximal tubule,
      suggesting that OTA may interfere with molecules involved in the regulation of
      cell division and apoptosis. In this study, treatment of immortalized human
      kidney epithelial (IHKE) cells with OTA (0-50 microM) resulted in a time- and
      dose-dependent increase in apoptosis and activation of c-Jun N-terminal kinase.
      At the same time, OTA blocked metaphase/anaphase transition and led to the
      formation of aberrant mitotic figures and giant cells with abnormally enlarged
      and/or multiple nuclei, sometimes still connected by chromatin bridges.
      Immunostaining of the mitotic apparatus using an alpha-tubulin antibody revealed
      defects in spindle formation. In addition, OTA inhibited microtubule assembly in
      a concentration-dependent manner in a cell-free, in vitro assay. Interestingly,
      treatment with OTA also resulted in activation of the transcription factor
      nuclear factor kappa B (NFkappaB), which has recently been shown to promote cell
      survival during mitotic cell cycle arrest. Based on these observations, we
      hypothesize that the mechanism by which OTA promotes tumor formation involves
      interference with microtubuli dynamics and mitotic spindle formation, resulting
      in apoptosis or-in the presence of survival signals such as stimulation of the
      NFkappaB pathway-premature exit from mitosis. Aberrant exit from mitosis
      resulting in blocked or asymmetric cell division may favor the occurrence of
      cytogenetic abnormalities and may therefore play a critical role in renal tumor
      formation by OTA.

PMID- 16641322
TI  - Exposure to a metabolite of the environmental toxicant, trichloroethylene,
      attenuates CD4+ T cell activation-induced cell death by metalloproteinase
      dependent FasL shedding.
AB  - Long-term exposure to the environmental contaminant trichloroethylene (TCE) in
      drinking water has been shown to promote autoimmune disease in association with
      the expansion of activated CD4+ T cells. The effects of TCE on CD4+ T cells were
      linked in the present study to the ability of TCE metabolite,
      trichloroacetaldehyde hydrate (TCAH), to inhibit activation-induced cell death
      (AICD) in CD4+ T cells. TCAH attenuated AICD in CD4+ T cells by decreasing FasL
      (CD178) expression but not by altering Fas (CD95) expression or by interfering
      with Fas-signaling events following direct engagement of the Fas receptor. The
      TCAH-induced decrease in FasL expression did not appear to be mediated at the
      transcriptional level but was instead due to increased shedding of FasL from the
      surface of the CD4+ T cells. The ability of TCAH to cleave FasL and thereby
      decrease AICD appeared to be mediated by metalloproteinases and correlated with a
      TCAH-induced increase in matrix metalloproteinase-7. Thus, this study presents
      the novel finding that the environmental contaminant TCE works via its metabolite
      TCAH to attenuate AICD by increasing metalloproteinase activity that cleaves FasL
      from CD4+ T cells. This represents a mechanism by which an environmental trigger
      inhibits AICD in CD4+ T cells and may thereby promote CD4+ T cell-mediated
      autoimmune disease.

PMID- 16641323
TI  - Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric
      partial seizures.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as
      adjunctive therapy in children (4 to 16 years) with treatment-resistant partial
      onset seizures. METHODS: This multicenter, randomized, placebo-controlled trial
      consisted of an 8-week baseline period followed by a 14-week double-blind
      treatment period. During the treatment period, patients received either placebo
      or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day.
      RESULTS: One hundred ninety-eight patients (intent-to-treat population) provided
      evaluable data. The reduction in partial-onset seizure frequency per week for LEV
      adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p =
      0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure
      frequency per week was attained in 44.6% of the LEV group (45/101 patients),
      compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%)
      LEV-treated patients were seizure-free during the entire double-blind treatment
      period, compared with one (1.0%) placebo-treated patient. One or more adverse
      events were reported by 88.1% of LEV-treated patients and 91.8% of placebo
      patients. The most common treatment-emergent adverse events were somnolence,
      accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough,
      and pharyngitis. A similar number of patients in each group required a dose
      reduction or withdrew from the study as a result of an adverse event. CONCLUSION:
      Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and
      well tolerated in children with treatment-resistant partial seizures.

PMID- 16641324
TI  - Neutralization potential determination of siderite (FeCO3) using selected
      oxidants.
AB  - Siderite (FeCO3) is commonly found in coal overburden and, when present, can
      cause interference in the determination of neutralization potential (NP). Under
      acidic testing conditions, FeCO3 reacts to neutralize acid, which contributes to
      the NP. However, continued weathering of FeCO3 (oxidation of Fe2+ and hydrolysis
      of Fe3+) produces a neutral to slightly acidic solution. The effects of hydrogen
      peroxide (H2O2), potassium permanganate (KMnO4), and O2 on the laboratory
      measurement of NP of siderite samples taken from overburden were examined. All
      oxidation treatments lowered the NP values of the siderite samples as compared
      with the standard USEPA method. However, oxidation with H2O2 produced variable
      results depending on the amount of H2O2 added. Neutralization potential values
      obtained after oxidation treatments were highly correlated with Mn concentration.
      Reaction products (i.e., 2-line ferrihydrite) of siderite samples with H2O2 and
      KMnO4 were not representative of natural siderite weathering. Oxidation with O2
      produced the lowest NP values for siderite samples. The reaction products
      produced by oxidation with O2 most closely represent those intermediate products
      formed when siderite is exposed to atmospheric weathering conditions. Oxidation
      with O2 also proved to be the most reproducible method for accurately assessing
      NP when siderite is present in overburden samples.

PMID- 16641325
TI  - Kinetics of base-catalyzed dehydrochlorination of hexachlorocyclohexanes: I.
      Homogeneous systems.
AB  - Base-catalyzed dehydrochlorination of alpha-, beta-, and gamma
      hexachlorocyclohexane (HCH) was examined at different pH and temperature
      conditions. No reaction was observed for beta-HCH under all tested conditions
      likely due to the fact that all chlorines are at the equatorial positions. Highly
      pH- and temperature-dependent reaction rates were observed for alpha- and gamma
      HCH, and pentachlorocyclohexenes (PCCHs) and 1,2,4- and 1,2,3-trichlorobenzene
      (TCB) were detected as the intermediates and final products of the transformation
      of both alpha- and gamma-HCH. The pseudo-first-order rate constants of each step
      of the reactions were calculated at different T and pH conditions. For the first
      step, the rate constants were at approximately 0.0005 d-1 in solutions below pH
      7.0, and increased by about an order of magnitude per pH unit from pH 7.01 to pH
      12.02. The second-order reaction rate constants (kb) of this step were 3.57+/
      0.03 and 3.19+/-0.19 M-1 d-1, respectively, and the associated activation
      energies (Ea) at pH 9.26 were 60.4+/-7.8 and 67.7+/-8.7 kJ mol-1, respectively,
      for alpha- and gamma-HCH. The rate constants for the formation of 1,2,3-TCB (k21)
      and 1,2,4-TCB (k22) were 0.0032+/-0.0001 d-1 and 0.051+/-0.003 d-1 from alpha
      HCH, and 0.0017+/-0.0001 d-1 and 0.0041+/-0.0002 d-1 from gamma-HCH at pH 8.28
      and 25 degrees C. Both k21 and k22 also showed an increase by about one order of
      magnitude per pH unit from pH 8.28 to pH 12.02. The Ea values were 64.4+/-6.8 and
      88.8+/-5.2 kJ mol-1, respectively, for the formation of 1,2,4-TCB and 1,2,3-TCB
      from alpha-HCH, and 70.6+/-8.7 and 92.0+/-4.9 kJ mol-1, respectively, for the
      formation of 1,2,4- and 1,2,3-TCB from gamma-HCH at pH 9.26. Data provided by
      this study may be used for calculation of the percentages of the TCBs formed at
      different environmental conditions.

PMID- 16641326
TI  - Identifying sources of fecal contamination inexpensively with targeted sampling
      and bacterial source tracking.
AB  - Most bacterial source tracking (BST) methods are too expensive for most
      communities to afford. We developed targeted sampling as a prelude to BST to
      reduce these costs. We combined targeted sampling with three inexpensive BST
      methods, Enterococcus speciation, detection of the esp gene, and fluorometry, to
      confirm the sources of fecal contamination to beaches on Georgia's Jekyll and Sea
      Islands during calm and stormy weather conditions. For Jekyll Island, the most
      likely source of contamination was bird feces because the percentage of Ent.
      faecalis was high (30%) and the esp gene was not detected. For the Sea Island
      beach during calm conditions, the most likely sources of fecal contamination were
      leaking sewer lines and wildlife feces. The leaking sewer lines were confirmed
      with fluorometry and detection of the esp gene. For the Sea Island beach during
      stormflow conditions, the most likely sources of fecal contamination were
      wildlife feces and runoff discharging from two county-maintained pipes. For the
      pipes, the most likely source of contamination was bird feces because the
      percentage of Ent. faecalis was high (30%) and the esp gene was not detected.
      Sediments were also a reservoir of fecal enterococci for both Jekyll and Sea
      Islands. Combining targeted sampling with two or more BST methods identified
      sources of fecal contamination quickly, easily, and inexpensively. This
      combination was the first time targeted sampling was conducted during stormy
      conditions, and the first time targeted sampling was combined with enterococcal
      speciation, detection of the esp gene, and fluorometry.

PMID- 16641327
TI  - Effects of a waste paper product on soil phosphorus, carbon, and bulk density.
AB  - Applications of manures to agricultural fields have increased soil test values
      for P to high levels in parts of the USA and thus increased the likelihood that P
      will be transported to surface water and degrade its quality. Waste paper
      applications to soils with high STP (soil test P) may decrease the risk of P
      transport to surface water by decreasing DRP (dissolved reactive P) by the
      formation of insoluble Al-P complexes and providing organic matter to improve
      infiltration. A field experiment was conducted near Booneville, AR (USA) to
      assess the effects of different rates of a waste paper product addition on STP,
      soil bulk density, and total soil C with a soil with approximately 45 mg Bray1-P
      kg-1 soil (dry weight). A Leadvale silt loam soil (fine-silty, siliceous, thermic
      Typic Fragiudult) was amended with 0, 22, 44, or 88 Mg waste paper product ha-1
      to supply approximately 90, 170, or 350 kg Al ha-1, respectively. One year after
      additions, there was a strong negative correlation between waste paper product
      application rates and soil bulk density, and a strong positive correlation
      between rates and total soil C content. Soil bulk density and total C 2 yr after
      additions, and soil DRP and Bray1-P were not affected by waste paper additions.
      These results support the hypothesis that decreases in DRP in runoff from soils
      receiving waste paper additions were probably due to changes in soil organic
      matter and bulk density, rather than changes in the chemical forms of soil P.

PMID- 16641328
TI  - Aerating grassland before manure application reduces runoff nutrient loads in a
      high rainfall environment.
AB  - The effect of mechanically aerating grassland before liquid manure application in
      the fall on surface runoff and transport of nutrients and solids was studied in a
      high rainfall area. The two treatments were control and aeration, the latter
      receiving one pass with an aerator perpendicular to the slope before fall
      application of liquid manure (dairy in Years 1-3 and swine in Year 4). Treatments
      were randomly assigned on 3 to 5% sloping land with a silt loam surface soil
      (Aquic Dystroxerept) planted in orchardgrass (Dactylis glomerata L.). Runoff from
      natural rainfall events was sampled for nutrient and solids analysis. Aeration
      significantly reduced runoff and loads of suspended solids, total Kjeldahl N
      (TKN), and dissolved reactive P in all years. Annual runoff amounts were reduced
      by 47 to 81%, suspended and volatile solid loads by 48 to 69% and 42 to 83%,
      respectively, TKN loads by 56 to 81%, and total P (TP) loads by 25 to 75%. Loads
      of the soluble nutrient NH4-N, dissolved reactive P, and K were reduced by 41 to
      83%. The first three runoff events after manure application accounted for
      approximately one-third of the annual total runoff and solid and nutrient loads
      when averaged across treatments, with loads of TKN, K, and NH4-N totaling 4.4,
      3.3, and 1.9 kg ha-1, respectively. Aeration slightly increased downward movement
      of NO3-N, but not other nutrients in the soil. Thus mechanical aeration can be an
      effective tool for reducing runoff and loads of solids and nutrients after
      surface application of liquid manure on sloping grassland.

PMID- 16641329
TI  - A novel extractant for removal of hazardous metals from preservative-treated wood
      waste.
AB  - The purpose of this study was to develop a one-step metal extraction process that
      would effectively remove hazardous elements from wood powder or chips of western
      hemlock [Tsuga heterophylla (Raf.) Sarg.] treated with chromated copper arsenate
      (CCA) preservative. In addition, we tested this method for wood treated with
      other copper-based preservatives such as ammoniacal copper quaternary (ACQ) and
      copper, boron, and azole (CuAz). A bioxalate solution consisting of 0.125 M
      oxalic acid adjusted to pH 3.2 with sodium hydroxide was tested for its ability
      to extract chromium, copper, and arsenic from wood treated with CCA and copper
      from ACQ, CuAz, or a mixture of CCA-, ACQ-, and CuAz-treated wood in single step.
      The extraction proceeded efficiently with 6 h of treatment, and was insensitive
      to the differences in chemical characteristics, including solubility of
      individual elements. After 6 h of treatment, approximately 90% of chromium,
      copper, and arsenic were effectively removed from wood treated with CCA or a
      mixture of CCA, ACQ, and CuAz and 90% of copper from ACQ- and CuAz-treated wood.
      These results demonstrate that the solvent extraction technique using pH-adjusted
      bioxalate solution with sodium hydroxide is a promising method for pollution
      minimization by various types of wastes contaminated with heavy metals and
      arsenic.

PMID- 16641330
TI  - Reducing phosphorus runoff from dairy farms.
AB  - Phosphorus (P) runoff from manure can lead to eutrophication of surface water and
      algae growth. This study evaluates the impacts of alternative P reduction
      practices on dairy farm net returns and on potential P runoff. The P control
      practices include dairy herd nutrient management, crop nutrient management, and
      runoff and erosion control. Four farms representative of dairies in the Virginia
      Shenandoah Valley are simulated including dairies with and without supplementary
      broiler enterprises and with average and below average land area. A mathematical
      programming model was developed to predict farm production and net returns and
      the GLEAMS model was used to predict potential P runoff. The farms are evaluated
      under four scenarios: Scenario 1, no constraint on P runoff with access to crop
      nutrient, runoff and erosion control strategies but no access to dairy herd
      nutrient control strategies; Scenario 2, no constraint on P runoff with access to
      all crop and dairy herd nutrient control strategies; Scenario 3, constraint on P
      runoff with access to crop nutrient, runoff and erosion control strategies but no
      access to dairy herd nutrient control strategies; and Scenario 4, constraint on P
      runoff with access to all crop and dairy herd nutrient control strategies. Under
      Scenario 2, the herd nutrient control strategies increase milk output per cow and
      net returns on both farms and reduce P content of manure and P runoff. Under
      Scenario 3, limiting P runoff reduces farm returns by 1 and 3% on the average and
      small farms, respectively. Under Scenario 4, the P runoff constraint is less
      costly, reducing returns by less than 1% on both farms. Animal nutrient control
      strategies should be an important part of pollution control policies and programs
      for livestock intensive watersheds.

PMID- 16641331
TI  - Predicting phosphorus availability from soil-applied composted and non-composted
      cattle feedlot manure.
AB  - Prediction of phosphorus (P) availability from soil-applied composts and manure
      is important for agronomic and environmental reasons. This study utilized
      chemical properties of eight composted and two non-composted beef cattle (Bos
      taurus) manures to predict cumulative phosphorus uptake (CPU) during a 363-d
      controlled environment chamber bioassay. Ten growth cycles of canola (Brassica
      napus L.) were raised in pots containing 2 kg of a Dark Brown Chernozemic clay
      loam soil (fine-loamy, mixed, Typic Haploboroll) mixed with 0.04 kg of the
      amendments. Inorganic P fertilizer (KH2PO4) and an unamended control were
      included for comparison. All treatments received a nutrient solution containing
      an adequate supply of all essential nutrients, except P, which was supplied by
      the amendments. Cumulative P uptake was similar for composted (74 mg kg-1 soil)
      and non-composted manures (60 mg kg-1 soil) and for the latter and the fertilizer
      (40 mg kg-1 soil). However, the CPU was significantly higher for organic
      amendments than the control (24 mg kg-1 soil) and for composted manure than the
      fertilizer. Apparent phosphorus recovery (APR) from composted manure (24%) was
      significantly lower than that from non-composted manure (33%), but there was no
      significant difference in APR between the organic amendments and the fertilizer
      (27%). Partial least squares (PLS) regression indicated that only two parameters
      [total water-extractable phosphorus (TPH2O) and total phosphorus (TP)
      concentration of amendments] were adequate to model amendment-derived cumulative
      phosphorus uptake (ACPU), explaining 81% of the variation in ACPU. These results
      suggest that P availability from soil-applied composted and non-composted manures
      can be adequately predicted from a few simple amendment chemical measurements.
      Accurate prediction of P availability and plant P recovery may help tailor manure
      and compost applications to plant needs and minimize the buildup of bioavailable
      P, which can contribute to eutrophication of sensitive aquatic systems.

PMID- 16641332
TI  - Assessment of the spatial distribution of soil properties in a northern
      Everglades marsh.
AB  - Florida Everglades restoration plans are aimed at maintaining and restoring
      characteristic landscape features such as soil, vegetation, and hydrologic
      patterns. This study presents the results from an exhaustive spatial sampling of
      key soil properties in Water Conservation Area 1 (WCA 1), which is part of the
      northern Everglades. Three soil strata were sampled: floc, upper 0- to 10-cm soil
      layer, and 10- to 20-cm soil layer. A variety of properties were measured
      including bulk density (BD), loss on ignition (LOI), total phosphorus (TP), total
      inorganic phosphorus (TIP), total nitrogen (TN), total carbon (TC), total iron
      (TFe), total magnesium (TMg), total aluminum (TAl), and total calcium (TCa).
      Interpolated maps and model prediction uncertainties of properties were generated
      using geostatistical methods. We found that the uncertainty associated with
      spatial predictions of floc, particularly floc BD, was highest, whereas spatial
      predictions of soil chemical properties such as soil Ca were more accurate. The
      resultant spatial patterns for these soil properties identified three predominant
      features in WCA 1: (i) a north to south gradient in soil properties associated
      with the predominant hydrological gradient, (ii) areas of considerable soil
      nutrient enrichment along the western canal of WCA 1, and (iii) areas of
      considerable Fe enrichment along the eastern canal. By using geostatistical
      techniques we were able to describe the spatial dynamics of soil variables and
      express these predictions with an acceptable level of uncertainty.

PMID- 16641335
TI  - Intraarterial MR angiography and DSA in patients with peripheral arterial
      occlusive disease: prospective comparison.
AB  - PURPOSE: To prospectively evaluate the accuracy of intraarterial magnetic
      resonance (MR) angiography in the depiction of significant stenoses and
      occlusions, with intraarterial digital subtraction angiography (DSA) serving as
      the reference standard. MATERIALS AND METHODS: Approval of the local ethics
      committee and informed consent were obtained. Twenty patients (11 men; nine
      women; age range, 48-86 years; mean age, 69.5 years+/-11.2 [standard deviation])
      with symptomatic peripheral arterial occlusive disease (PAOD) were prospectively
      enrolled. After percutaneous transluminal angioplasty (PTA), intraarterial MR
      angiography was performed in the thigh and the calf with a 1.5-T MR imager in two
      consecutive runs. Intraarterial MR angiography was performed with a low-dose
      injection protocol (ie, two 20-mL injections of a 50-mmol gadolinium-based
      contrast agent). Moderate stenoses (luminal narrowing<or=50%), significant
      stenoses (luminal narrowing 51%-99%), and occlusions (luminal narrowing of 100%)
      were identified on MR angiograms, which were compared with intraarterial DSA
      images. Intraarterial MR angiograms were analyzed for imaging artifacts.
      Sensitivity, specificity, accuracy, and positive and negative predictive values
      of intraarterial MR angiography with intraarterial DSA were determined for
      characterization of significant stenoses (>50%) or vessel occlusions; 95%
      confidence intervals (CIs) were calculated for sensitivity and specificity.
      RESULTS: Intraarterial DSA revealed 78 moderate stenoses, 57 significant
      stenoses, and 28 occlusions. Sensitivity, specificity, and accuracy of
      intraarterial MR angiography in the characterization of significant stenoses or
      occlusions were 92% (95% CI: 72%, 99%), 94% (95% CI: 82%, 98%), and 93%,
      respectively, in femoropopliteal arteries and 93% (95% CI: 83%, 98%), 71% (95%
      CI: 51%, 86%), and 86%, respectively, in infrapopliteal arteries. The main
      artifact observed with intraarterial MR angiography was venous contamination
      (12%). CONCLUSION: Intraarterial MR angiography is an accurate method used to
      depict significant stenoses and occlusions in lower extremity arteries with a low
      dose injection protocol.

PMID- 16641336
TI  - Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR
      spectroscopy, relaxation times, and apparent diffusion coefficients.
AB  - PURPOSE: To retrospectively evaluate magnetic resonance (MR) imaging, hydrogen 1
      (1H) MR spectroscopy, apparent diffusion coefficient (ADC), T1, and T2
      measurements for prediction of late neurologic outcome in term neonates after
      severe perinatal asphyxia. MATERIALS AND METHODS: This study was approved by the
      local ethics committee. Informed consent from parents was not required. Thirty
      term neonates (12 boys, 18 girls; age range, 2-12 days) with severe hypoxic
      ischemic encephalopathy were examined during the first 12 days of life with
      conventional and diffusion-weighted cerebral MR imaging, 1H MR spectroscopy with
      absolute quantification, and T1 and T2 measurements. Quantitative 1H MR
      spectroscopy, T1, and T2 data were acquired on one 10-mm slab positioned at the
      level of the basal ganglia. The neonates were assigned to one of two groups
      according to their late (>12-month follow-up) neurologic outcome: those with an
      unfavorable outcome-that is, death or severe disability-and those with a
      favorable outcome. Clinical data, MR signal intensity abnormalities, ADCs, 1H MR
      spectroscopy findings, and relaxation times were compared by using Chi2 testing
      and analysis of variance to individualize the prognostic indicators. RESULTS: The
      unfavorable (n=16) and favorable (n=14) outcome groups were similar in terms of
      clinical data (ie, Apgar scores, visceral hypoxic injuries), visualization of
      brain edema on MR images, and T1 and T2 relaxation times. Late unfavorable
      neurologic outcome was associated with a mixed pattern of cortical and basal
      ganglia signal intensity abnormalities on MR images (13 babies with unfavorable
      vs three babies with favorable outcomes, P=.001) and with decreased absolute N
      acetylaspartate (NAA) and choline concentrations in all brain structures,
      especially the basal ganglia (mean NAA concentration: 2.72 mmol/L in unfavorable
      outcome group vs 4.66 mmol/L in favorable outcome group, P<5x10(-9)), as measured
      with MR spectroscopy. In the basal ganglia, an NAA concentration lower than 4
      mmol/L indicated an unfavorable individual prognosis with 94% sensitivity and 93%
      specificity. Significantly reduced ADCs also were noted in the unfavorable
      outcome group, but only during the first 6 days of life. CONCLUSION: Conventional
      MR imaging findings, spectroscopically measured absolute NAA and choline
      concentrations, and ADCs are complementary tools for predicting the individual
      outcomes of severely asphyxiated term neonates.

PMID- 16641337
TI  - Pulse-inversion US imaging of testicular ischemia: quantitative and qualitative
      analyses in a rabbit model.
AB  - PURPOSE: To quantitatively and qualitatively assess perfusion with pulse
      inversion (PI) ultrasonography (US) in rabbit model of acute testicular ischemia.
      MATERIALS AND METHODS: Institutional animal care committee approval was obtained.
      After 35 rabbits underwent unilateral spermatic cord occlusion, testicular
      Doppler US and contrast material-enhanced PI imaging were performed. Enhancement
      data yielded perfusion measurements including mean value during the first 10
      seconds, mean value over entire recorded replenishment curve, and curve slope
      during the first 5 seconds. Calculated perfusion ratios were compared with
      radiolabeled microsphere-derived perfusion ratios. Two readers assessed
      testicular perfusion as none, possible, or definite and relative perfusion as
      greater to the right testis than to the left, greater to the left testis than to
      the right, or as equal to both testes. With kappa statistics, interobserver
      agreement for all imaging methods was determined. Association between qualitative
      perfusion categories and radiolabeled microsphere-based perfusion measurements
      was assessed. Quantitative and qualitative determinations of relative perfusion
      were compared with radiolabeled microsphere-based measurements. RESULTS:
      Correlations between calculated and radiolabeled microsphere-based perfusion
      ratios were determined (r=0.49-0.64). Interobserver agreement for presence of
      perfusion was excellent (kappa=0.76), and that for relative perfusion assessment
      was good (kappa=0.55). Neither kappa value varied significantly with imaging
      method. The percentage of times a testis classified as having definite perfusion
      had greater perfusion as measured with radiolabeled microspheres than a testis
      classified as having no perfusion or possible perfusion was higher with PI
      imaging than with Doppler US (85%-98% vs 72%-89%). Identification of the testis
      with less perfusion was better with quantitative methods than with qualitative
      assessment of images by the readers (75%-79% vs 34%-60%, P<.004). CONCLUSION: PI
      imaging, compared with conventional Doppler US methods, provides superior
      assessment of perfusion in the setting of acute testicular ischemia.

PMID- 16641338
TI  - Cine delayed-enhancement MR imaging of the heart: initial experience.
AB  - This study was performed by using an institutional review board-approved
      protocol, with waived informed consent and HIPAA compliance. The purpose of this
      study was to preliminarily evaluate a cine delayed-enhancement (DE) pulse
      sequence for depiction of wall motion and myocardial scar extent during a single
      acquisition. The technique is based on inversion-recovery single-shot balanced
      steady-state free precession magnetic resonance imaging. Cine DE images were
      acquired in 26 patients (18 men, eight women; age range, 25-84 years; mean age,
      61 years+/-13 [standard deviation]). Image contrast was consistent throughout
      each series. Overall (ie, with both readers' scores averaged), the cine DE
      imaging-depicted wall motion was scored correctly in 71% of myocardial segments.
      Scar extent was scored correctly in 76% of segments; in no patient was scarring
      missed. Cine DE imaging is a promising technique for simultaneous visualization
      of wall motion and myocardial scar extent.

PMID- 16641339
TI  - Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at
      3.0 T.
AB  - PURPOSE: To prospectively determine whether diffusion-tensor magnetic resonance
      (MR) imaging in conjunction with two-dimensional chemical shift imaging can
      assist in identifying upper motor neuron involvement and whether disease severity
      and duration can be predicted based on imaging parameters in patients with
      amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Institutional review
      board approval and informed consent were obtained for this HIPAA-compliant study.
      Fifteen patients with ALS (12 men, three women; mean age, 57.3 years) with
      clinical evidence of upper motor neuron involvement and 10 healthy control
      subjects (five men and five women; mean age, 49.4 years) were studied. Fractional
      anisotropy (FA) and apparent diffusion coefficient (ADC) were measured from the
      corticospinal tracts at the level of the internal capsule. Average N
      acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline-containing
      compounds (Cho) ratios were calculated from the precentral gyrus. Student t test,
      multiple linear regression analysis, and Spearman correlation coefficients were
      employed to quantify relationships between imaging and clinical parameters.
      RESULTS: Patients with ALS exhibited significantly reduced FA values and NAA/Cr
      and NAA/Cho ratios compared with values in control subjects (P<.05) for both
      affected and nonaffected sides of the brain. ADC was elevated significantly in
      the affected side (P<.05) and was an independent predictor of disease duration
      after adjusting for age; however, FA values and NAA/Cr ratios for the affected
      side were even stronger predictors of disease duration. Moderate but
      statistically significant correlation was found between the FA values for the
      affected side and the ALS Functional Rating Scale Revised (ALSFRS-R) score
      (r=0.51, P<.05). The NAA/Cr ratio also correlated with both the ALSFRS-R and
      upper motor neuron scores (r=0.50 and 0.54, respectively; P<.05). CONCLUSION:
      Diffusion-tensor and two-dimensional chemical shift MR imaging spectroscopy can
      be used to identify upper motor neuron involvement and predict disease duration
      in patients with ALS.

PMID- 16641340
TI  - Radiographic findings of osteoarthritis versus arthroscopic findings of articular
      cartilage degeneration in the tibiofemoral joint.
AB  - PURPOSE: To retrospectively correlate radiographic findings of osteoarthritis of
      the tibiofemoral joint with arthroscopic findings of articular cartilage
      degeneration within the tibiofemoral joint in patients with chronic knee pain.
      MATERIALS AND METHODS: The study was performed in compliance with HIPAA
      regulations. Approval from an institutional review board and a waiver of informed
      consent were obtained. The study group consisted of 125 patients with
      osteoarthritis of the tibiofemoral joint (66 men, 59 women; age range, 35-77
      years; average age, 52 years) and 25 patients of similar age (14 men, 11 women;
      age range, 36-69 years; average age, 50 years) with no osteoarthritis of the
      tibiofemoral joint. All patients underwent standing anteroposterior radiography
      of the knee prior to arthroscopic knee surgery. Each articular surface of the
      tibiofemoral joint was graded at arthroscopy. Two radiologists retrospectively
      reviewed the knee radiographs to determine the presence of marginal osteophytes,
      joint space narrowing, subchondral sclerosis, and subchondral cysts. The
      sensitivity and specificity of the radiographic features of osteoarthritis for
      the detection of articular cartilage degeneration within the medial and lateral
      compartments of the tibiofemoral joint were determined. RESULTS: The sensitivity
      of marginal osteophytes, joint space narrowing, subchondral sclerosis, and
      subchondral cysts for the detection of articular cartilage degeneration was 67%,
      46%, 16%, and 10%, respectively, for the medial compartment and 49%, 7%, 6%, and
      3%, respectively, for the lateral compartment. The specificity of marginal
      osteophytes, joint space narrowing, subchondral sclerosis, and subchondral cysts
      for the detection of articular cartilage degeneration was 73%, 95%, 100%, and
      100%, respectively, for the medial compartment and 81%, 100%, 100%, and 100%,
      respectively, for the lateral compartment. CONCLUSION: Marginal osteophytes were
      the most sensitive radiographic feature for the detection of osteoarthritis of
      the tibiofemoral joint. Joint space narrowing, subchondral sclerosis, and
      subchondral cysts were less sensitive radiographic features of osteoarthritis and
      rarely occurred in the absence of associated osteophyte formation.

PMID- 16641341
TI  - Myocardial viability: assessment with three-dimensional MR imaging in pigs and
      patients.
AB  - PURPOSE: To prospectively evaluate the correlation between a three-dimensional
      (3D) delayed enhancement magnetic resonance (MR) imaging sequence and a two
      dimensional (2D) delayed enhancement MR imaging sequence for noninvasive
      assessment of myocardial viability in pigs and patients. MATERIALS AND METHODS:
      The pig and patient studies were approved by the responsible authorities, and
      patients gave written informed consent. MR imaging was performed by using a rapid
      3D inversion-recovery balanced steady-state free precession sequence and a 2D
      segmented inversion-recovery fast low-angle shot sequence as the reference
      standard. Fourteen pigs with reperfused (n=7) or nonreperfused (n=7) myocardial
      infarction and 17 patients (13 men, four women; mean age, 64.9 years+/-8.6
      [standard deviation]) suspected of having myocardial infarction were included.
      Linear regression analysis and Bland-Altman analysis were used to compare the
      infarction volumes. RESULTS: In 10 of the 14 pigs the induction of myocardial
      infarction was successful. In these pigs, altogether 81 segments with myocardial
      infarction were demonstrated by both MR sequences, and agreement between the two
      sequences for classification of transmural extent of myocardial infarction was
      99.7%. The infarction volume determined by using 3D MR imaging (4.64 cm3+/-2.48)
      in the pigs highly correlated with that of 2D MR imaging (4.65 cm3+/-2.39,
      r=0.989, P<.001) and that of staining by using triphenyltetrazolium chloride
      (4.67 cm3+/-2.44, r=0.996, P<.001). Thirteen of the 17 patients examined showed
      myocardial infarction in 34 myocardial segments with both sequences, and
      agreement between the two sequences for classification of transmural extent of
      myocardial infarction was 98.6%. In the patients, the infarction volume
      determined with both sequences highly correlated (9.71 cm3+/-7.47 for the 3D
      sequence vs 10.01 cm3+/-8.04 for the 2D sequence, r=0.982, P<.001). The breath
      hold time necessary for the 3D MR imaging (21.0+/-2.3 seconds) was significantly
      shorter than that for 2D MR imaging (188.3+/-20.2 seconds, P<.001). CONCLUSION:
      Myocardial infarction volumes obtained with the 3D MR imaging sequence are highly
      correlated and in good agreement with volumes obtained with the 2D MR imaging
      standard approach and reduced the acquisition time by a factor of nine.

PMID- 16641342
TI  - Peripheral arteries: treatment with antibodies of platelet receptors and
      reteplase for thrombolysis--APART trial.
AB  - PURPOSE: To prospectively compare the safety and efficacy of combination therapy
      with the glycoprotein IIb/IIIa antagonist abciximab plus the third-generation
      thrombolytic agent reteplase versus those of therapy with the standard
      thrombolytic agent urokinase plus abciximab. MATERIALS AND METHODS: The study was
      approved by the local ethics committee, and patient informed consent was
      obtained. Patients with peripheral arterial occlusions less than 60 days old
      (n=120) were enrolled in the study: 50 patients (32 men, 18 women; mean age, 67
      years; range, 23-88 years) received reteplase plus abciximab and 70 patients (36
      men, 34 women; mean age, 68 years; range, 28-88 years) received urokinase plus
      abciximab. Study end points were the rate of major complications at 30 days,
      therapeutic success, and survival without open surgery or major amputation at
      follow-up. Fisher exact test was used to compare treatment groups with respect to
      dichotomous variables, and the event-free-survival probabilities were calculated
      with the Kaplan-Meier method. For the comparison of the lengths of occlusions
      among the groups, a two-sample t test was used. RESULTS: Therapeutic success
      (P=.7) did not differ between the groups, whereas the time required for
      thrombolysis was lower in the urokinase-plus-abciximab group (P=.001). Patients
      who received reteplase plus abciximab tended to develop more minor complications
      (mainly bleeding events) (P<.001). During long-term follow-up (2-4 years), no
      group differences were observed. The reocclusion rate was 48% (22 of 46) in the
      reteplase-plus-abciximab group and 45% (29 of 64) in the urokinase-plus-abciximab
      group. Only two of 120 major amputations were counted in the follow-up period.
      CONCLUSION: The proposed regimen resulted in only a limited number of major
      complications, and the low amputation rate in both groups may be attributed to
      abciximab.

PMID- 16641343
TI  - Financial disclosures of scientific papers presented at the 2003 RSNA Annual
      Meeting: association with reporting of non-Food and Drug Administration-approved
      uses of industry products.
AB  - PURPOSE: To retrospectively characterize the extent and nature of financial
      relationships with industry that are disclosed in the abstracts of scientific
      papers presented at the 2003 Radiological Society of North America (RSNA) Annual
      Meeting and to retrospectively assess whether the presence of relationships
      between researchers and industry was associated with a discussion on the use of
      products or devices that are not yet approved by the U.S. Food and Drug
      Administration (FDA). MATERIALS AND METHODS: Printed abstracts of scientific
      papers published in the 2003 Radiological Society of North America Scientific
      Assembly and Annual Meeting Program were classified according to the number and
      type of financial relationships disclosed. Also recorded was whether the
      abstracts discussed non-FDA-approved use of a product. Abstracts with and those
      without disclosures were then compared by using the Fisher exact test with
      respect to the percentage of abstracts that reported non-FDA-approved use.
      RESULTS: Of the 1549 published abstracts, 271 (17%) disclosed at least one author
      with financial ties to a company whose products or services were reported. The
      most common disclosures were for authors who were employees (39%), corporate
      grant recipients (34%), corporate consultants (23%), or shareholders (18%) of the
      corporation whose product was studied. A total of 87 (32%) of 271 abstracts with
      disclosed corporate relationships discussed non-FDA-approved use of a commercial
      product compared with 197 (15%) of 1278 abstracts with no disclosed tie to
      industry (P<.001). CONCLUSION: RSNA abstracts in which authors disclosed
      corporate financial relationships were twice as likely as those without such
      disclosures to discuss non-FDA-approved use of a commercial product. This raises
      the possibility that corporate relationships may influence radiology research.

PMID- 16641344
TI  - Lesion detection and characterization in a breast US phantom: results of the
      ACRIN 6666 Investigators.
AB  - PURPOSE: To prospectively evaluate ultrasonographic (US) lesion detection and
      characterization in a breast phantom by potential investigators in a screening US
      protocol, American College of Radiology Imaging Network (ACRIN) 6666. MATERIALS
      AND METHODS: National Cancer Institute Cancer Experimental Therapeutic Protocol
      review and ACRIN internal institutional review board approved the protocol;
      potential investigators were informed of the study purpose prior to
      participation. Six equivalent anthropomorphic phantoms were prepared with 17
      masses (2-10 mm in mean diameter) in different locations at different depths.
      Sixty-six investigators, experienced in breast US, from 23 institutions scanned a
      phantom with high-frequency linear-array transducers (12-5 MHz). Lesion location,
      diameters, echogenicity, shape, and posterior features were recorded. Reader
      specific phantom maps were generated and compared with known lesion locations and
      features. Results from 64 observers could be analyzed and were masked to
      investigator identity. Agreement on US features was measured with kappa
      statistics. A generalized linear model generated log relative risks for detection
      rates as a function of lesion diameter, depth, and features. RESULTS: Of 17
      lesions, a median of 14 (82%) were detected (range, 9-16), and 86% of observers
      detected at least 12 lesions. Of 1088 potential detections, 861 (79.1%) were
      made. Among 5-10-mm lesions, 499 (97.5%) of 512 detections were made (excluding a
      6-mm "skin" lesion seen by only seven observers [11%]). One 4-mm mass was seen by
      53 observers (83%). Among 3-mm lesions, 274 (71.4%) of 384 detections were made.
      One 2-mm lesion was seen by 28 (44%) observers. Relative risk of detection
      decreased to 0.55 (95% confidence interval: 0.51, 0.59) for each centimeter
      increase in lesion depth. Agreement was slight for lesion shape (kappa=0.14),
      substantial for echogenicity (kappa=0.61), and moderate for posterior features
      (kappa=0.45). Feature description errors were common for 2-4-mm lesions; only 33%
      of 3-mm anechoic masses were so characterized. Among eight 6-10-mm lesions,
      investigators erred in feature description of a median of 1 lesion (mean, 1.3;
      range, 0-4). CONCLUSION: US detection and description of lesions in a breast
      phantom were highly consistent for lesions 5-10 mm in diameter; those smaller
      than 5 mm were less reliably identified or characterized by experienced
      investigators.

PMID- 16641346
TI  - Science to Practice: Can MR imaging replace liver biopsy for the diagnosis of
      early fibrosis?

PMID- 16641345
TI  - Anthropomorphic breast phantoms for qualification of Investigators for ACRIN
      Protocol 6666.
AB  - The purpose of this study was to evaluate various ultrasonic properties of breast
      phantoms developed for use in qualifying investigators for participation in the
      American College of Radiology Imaging Network (ACRIN) protocol 6666, "Screening
      Breast Ultrasound in High-Risk Women." Specifically, a tool was sought to
      consistently measure the performance of radiology personnel in detecting and
      characterizing lesions similar to those expected with screening breast
      ultrasonography (US). The phantoms are equivalent to one another except for the
      randomization of positions of 14 of the 17 simulated lesions. The lesions differ
      in depth and ultrasonic properties. Representative values of propagation speed,
      attenuation, relative echogenicity, and mass density are reported for all tissue
      mimicking components. Beam refraction occurs at the interface between the
      subcutaneous fat layer and the glandular parenchyma and can result in beam
      distortion artifacts similar to those encountered in clinical breast US.

PMID- 16641348
TI  - Incidence of colonic perforation at CT colonography: review of existing data and
      implications for screening of asymptomatic adults.

PMID- 16641349
TI  - Advice for optimizing colonic distention and minimizing risk of perforation
      during CT colonography.

PMID- 16641350
TI  - Dynamic CT measurement of pulmonary enhancement in piglets with experimental
      acute respiratory distress syndrome.
AB  - PURPOSE: To investigate whether analysis of a washout curve of contrast material
      obtained with serial computed tomography (CT) enables differentiation between
      hydrostatic pulmonary edema and pulmonary edema caused by increased capillary
      permeability. MATERIALS AND METHODS: The institutional committee on animal
      experiments approved this study, which was performed in accordance with
      designated guidelines. Chest CT was performed in 12 piglets after induction of
      anesthesia and start of mechanical ventilation. Dynamic CT was performed before
      and after induction of hydrostatic edema (n = 5) or oleic acid-induced increased
      vascular permeability edema (n = 7). Scans were obtained over 240 seconds during
      inspiratory breath holding at a single representative subcarinal level in the
      lungs. This anatomic level was kept constant and included areas of normal
      ventilation before and after induction of pulmonary edema and areas of ground
      glass opacity and consolidation after induction of pulmonary edema. Measured lung
      attenuation in the regions of interest was normalized to that before contrast
      material injection and plotted as a function of time. Statistical analysis was
      performed by using two-way analysis of variance with repeated measures. RESULTS:
      In general, before induction of pulmonary edema, attenuation of normally aerated
      lung areas did not increase after the initial peak of enhancement during the
      first pass of contrast material. In animals with hydrostatic edema, no
      attenuation changes in areas of ground-glass opacity were observed after the
      initial peak. Conversely, lung attenuation increased continuously in animals with
      oleic acid-induced high-permeability pulmonary edema (P = .002). After induction
      of lung edema, pulmonary enhancement measured in lung regions with normal
      ventilation or consolidation did not change in either group. Pulmonary fluid
      accumulation 90 minutes after induction of edema did not significantly differ
      between groups. CONCLUSION: Dynamic contrast-material enhanced CT can help
      differentiate between permeability and hydrostatic lung edema in an animal model.

PMID- 16641351
TI  - Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus
      nonionic contrast agent.
AB  - PURPOSE: To determine whether there are differences in the distribution of ionic
      and nonionic gadolinium-based contrast agents by evaluating contrast enhancement
      of the physis, epiphyseal cartilage, secondary ossification center, and
      metaphysis in the knees of normal piglets. MATERIALS AND METHODS: Following
      approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old
      piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous
      injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate
      dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with
      gradient-echo MR imaging was quantified and compared (Student t test) by means of
      enhancement ratios. Distribution of contrast material was assessed and compared
      (Student t test) by means of T1 measurements obtained before and at three 15
      minute intervals after contrast agent administration. The relative visibility of
      the physis, epiphyseal cartilage, secondary ossification center, and metaphysis
      was qualitatively assessed by two observers and compared (Wilcoxon signed rank
      test). Differences in matrix content and cellularity that might explain the
      imaging findings were studied at histologic evaluation. RESULTS: Enhancement
      ratios were significantly higher for gadoteridol than for gadopentetate
      dimeglumine in the physis, epiphyseal cartilage, and secondary ossification
      center (P < .05). After contrast agent administration, T1 values decreased
      sharply for both agents-but more so for gadoteridol. Additionally, there was less
      variability in T1 values across structures with this contrast agent. Gadoteridol
      resulted in greater visibility of the physis, while gadopentetate dimeglumine
      resulted in greater contrast between the physis and metaphysis (P < .05).
      CONCLUSION: The results suggest different roles for the two gadolinium-based
      contrast agents: The nonionic contrast medium is better suited for evaluating
      perfusion and anatomic definition in the immature skeleton, while the ionic
      contrast medium is better for evaluating cartilage fixed-charge density.

PMID- 16641352
TI  - Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR
      imaging.
AB  - PURPOSE: To retrospectively evaluate the accuracy of double contrast material
      enhanced (hereafter double-enhanced) magnetic resonance (MR) imaging depiction of
      hepatic fibrosis, with histopathologic analysis findings as the reference
      standard. MATERIALS AND METHODS: The institutional review board approved this
      HIPAA-compliant study and waived the requirement for informed consent. One
      hundred one patients (58 men, 43 women; mean age +/- standard deviation, 52 years
      +/- 10) who underwent double-enhanced MR imaging with superparamagnetic iron
      oxide (SPIO)-enhanced and double-enhanced spoiled gradient-echo (SPGR) sequences
      between 2001 and 2004 and had a reliable reference standard for the diagnosis of
      liver fibrosis were included. Two blinded MR radiologists retrospectively scored
      qualitative (reticulation, nodularity, and total scores) and quantitative
      (contrast-to-noise ratio between hyperintense and hypointense liver regions,
      coefficient of variation, and noise-corrected coefficient of variation) liver
      texture features on MR images in consensus. The image scores for patients with
      advanced (METAVIR fibrosis score >/= 3) versus those for patients with mild
      (METAVIR score </= 2) fibrosis were compared, and receiver operating
      characteristic curves were determined. Diagnostic performance values were
      calculated at the optimal operating point. Mann-Whitney U and unpaired Student t
      tests were performed. RESULTS: Qualitative and quantitative image scores were
      significantly higher for patients with METAVIR fibrosis scores of 3 or higher
      than for those with scores of 2 or lower (P < .001); on SPIO-enhanced SPGR
      images, differences increased with increasing echo time. Diagnostic performance
      for detection of grade 3 or more severe fibrosis was better with the double
      enhanced sequence than with the SPIO-enhanced sequences, and qualitative scores
      had higher diagnostic performance than quantitative scores. The sensitivity,
      specificity, and accuracy of qualitative scores on double-enhanced SPGR images
      were higher than 90%. CONCLUSION: Advanced hepatic fibrosis can be detected by
      using double-enhanced MR imaging. Although diagnostic performance depended on the
      sequence and scoring system used, sensitivity, specificity, and accuracy values
      higher than 90% were achievable.

PMID- 16641353
TI  - Hepatocellular carcinoma in the cirrhotic liver: gadolinium-enhanced 3D T1
      weighted MR imaging as a stand-alone sequence for diagnosis.
AB  - PURPOSE: To retrospectively assess the usefulness of contrast material-enhanced
      T1-weighted magnetic resonance (MR) imaging alone and with T2-weighted MR imaging
      in the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A
      waiver of informed consent and institutional review board approval for this
      retrospective study were granted. The study was HIPAA compliant. Twenty-eight men
      (mean age, 49 years; range, 23-70 years) and 10 women (mean age, 53 years; range,
      42-72 years) with cirrhosis underwent T2-weighted and contrast-enhanced T1
      weighted MR imaging at 1.5 T within 90 days of liver transplantation. Three
      readers reviewed the T1-weighted images alone and then the T2-weighted and T1
      weighted images together. Lesion detection, characterization, and reader
      confidence levels were recorded. RESULTS: At liver explantation, 57 lesions were
      present in 18 patients: 19 HCCs, 33 dysplastic nodules, and five cysts. Contrast
      enhanced T1-weighted imaging depicted 13 of 19 HCCs with an overall sensitivity
      of 68.4% (13 of 19) and specificity of 65.7% (23 of 35). The sensitivity and
      specificity for detection of dysplastic nodules (sensitivity, 9%; specificity,
      68.4%) and HCCs (sensitivity, 68.4%; specificity, 65.7%) were nearly identical
      for T1-weighted images read alone or read with T2-weighted images. The only
      difference was the specificity for T1-weighted images read alone (65.7%) and read
      with T2-weighted images (62.9%). The addition of T2-weighted images altered the
      diagnosis in one of 90 (1.1%) cases and provided an increase in diagnostic
      confidence in four of 258 (1.6%) cases for independent readers and three of 90
      (3.3%) cases at consensus reading. CONCLUSION: Contrast-enhanced T1-weighted
      imaging can be used as a stand-alone sequence for the diagnosis of HCC in
      patients with cirrhosis prior to liver transplantation.

PMID- 16641354
TI  - Prostate cancer evaluated with ferumoxtran-10-enhanced T2*-weighted MR Imaging at
      1.5 and 3.0 T: early experience.
AB  - PURPOSE: To prospectively evaluate the feasibility of ferumoxtran-10-enhanced
      magnetic resonance (MR) imaging at high magnetic field strength (3.0 T) and to
      compare image quality between 1.5- and 3.0-T MR imaging in terms of lymph node
      detection in patients with prostate cancer. MATERIALS AND METHODS: This study was
      institutional review board approved, and all patients gave written informed
      consent. Forty-eight consecutive patients aged 51-79 years (mean, 65.5 years)
      with prostate cancer were enrolled. T2*-weighted 1.5- and 3.0-T MR images of the
      pelvis were acquired in a sagittal plane parallel to the psoas muscle 24 hours
      after ferumoxtran-10 administration. A pelvic and body phased-array coil was used
      and yielded an in-plane resolution of 0.56 x 0.56 x 3.00 mm at 1.5 T and 0.50 x
      0.50 x 2.50 mm at 3.0 T. All images were evaluated by three readers for total
      image quality, lymph node border delineation, muscle-fat contrast, and vessel-fat
      contrast. Statistical significance was calculated by using the Mann-Whitney U
      test. Subsequently, the general linear mixed model was used to estimate the
      contributions of three factors-patient, reader, and technique-to the variability
      of the imaging results. RESULTS: Significantly (P < .05) better muscle-fat
      contrast, vessel-fat contrast, lymph node border delineation, and total image
      quality were observed at 3.0-T MR imaging. The general linear mixed model
      revealed that the variability of all results could be attributed to the use of
      3.0-T imaging. CONCLUSION: Ferumoxtran-10-enhanced MR imaging can be performed at
      high magnetic field strengths and result in improved image quality, which may
      lead to improved detection of small positive lymph nodes.

PMID- 16641355
TI  - Supratentorial low-grade glioma resectability: statistical predictive analysis
      based on anatomic MR features and tumor characteristics.
AB  - PURPOSE: To retrospectively assess the main variables that affect the complete
      magnetic resonance (MR) imaging-guided resection of supratentorial low-grade
      gliomas. MATERIALS AND METHODS: Institutional review board approval was obtained
      for this retrospective HIPAA-compliant study, with the requirement for informed
      consent waived. Data from 101 patients (61 men, 40 women; mean age, 39 years; age
      range, 18-72 years) who had nonenhancing supratentorial mass lesions that were
      histopathologically diagnosed as low-grade (World Health Organization grade II)
      gliomas and consecutively underwent surgery with intraoperative MR imaging
      guidance were analyzed. There were 21 low-grade astrocytomas, 64
      oligodendrogliomas, and 16 mixed oligoastrocytomas. Initial and residual tumor
      volumes were measured on intraoperative T2-weighted MR images and three
      dimensional spoiled gradient-echo MR images. The anatomic relationships between
      the tumor and eloquent cortical and/or subcortical regions and the influence of
      these relationships on the extent of resection were analyzed on the basis of
      preoperative MR imaging findings. Summary measures, univariate Fisher exact test
      and t test, and multivariate logistic regression analyses were performed.
      RESULTS: Tumor volume ranged from 2.7-231.0 mL. Univariate analyses revealed the
      following tumor characteristics to be significant predictive variables of
      incomplete tumor resection: diffuse tumor margin on T2-weighted MR images,
      oligodendroglioma or oligoastrocytoma histopathologic type, and large tumor
      volume (P < .05 for all). Tumor involvement of the following structures was
      associated with incomplete resection: corpus callosum, corticospinal tract,
      insular lobe, middle cerebral artery, motor cortex, optic radiation, visual
      cortex, and basal ganglia (P < .05 for all). Multivariate analyses revealed that
      incomplete tumor resection was due to tumor involvement of the corticospinal
      tract (P < .01), large tumor volume (P < .01), and oligodendroglioma
      histopathologic type (P = .02). CONCLUSION: The main variables associated with
      incomplete tumor resection in 101 patients were identified by using statistical
      predictive analyses.

PMID- 16641356
TI  - Distinguishing benign from malignant pulmonary nodules with helical chest CT in
      children with malignant solid tumors.
AB  - PURPOSE: To retrospectively assess whether computed tomographic (CT) findings can
      indicate the benign or malignant nature of pulmonary nodules in pediatric
      patients with malignant solid primary tumors. MATERIALS AND METHODS: With
      institutional review board approval, waived parental and patient consent, and
      HIPAA compliance, the authors determined the incidence of malignancy among 81
      pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT
      (January 1999 to September 2003) in 41 young patients with malignant solid
      tumors. Three radiologists independently and retrospectively reviewed these scans
      and the available previously obtained scans, classifying nodules as benign,
      malignant, or indeterminate on the basis of their number, unilateral versus
      bilateral distribution, size, margins (indistinct vs distinct), calcification,
      growth, and associated adenopathy. These classifications were compared with
      nodule histologic type, and interreviewer agreement was assessed. RESULTS: The
      median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty
      four of the 41 patients (58%) had at least one biopsy-proved malignant nodule.
      Four (10%) patients had both benign and malignant nodules; 17 (42%) had only
      benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly;
      reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer
      agreement was slight to moderate (kappa </= 0.43, P </= .03). In contrast to
      findings in adults, sharply defined nodules in younger individuals were more
      likely to be malignant (P = .03) and nodule size was not associated with
      malignancy (P >/= .32). CONCLUSION: The frequency of benign nodules and the
      inconsistency of predictions based on CT features suggest the need for better
      predictors of pulmonary nodules being malignant or benign, so as to reduce
      unnecessary thoracotomy in pediatric patients with solid malignancy. .

PMID- 16641357
TI  - CT screening for lung cancer: prevalence and incidence of mediastinal masses.
AB  - PURPOSE: To determine the frequency and natural course of mediastinal masses in
      asymptomatic people at high risk for lung cancer who were undergoing computed
      tomographic (CT) screening. MATERIALS AND METHODS: Informed consent and
      institutional review board approval for this HIPAA-compliant study were obtained
      at each participating institution. All documented mediastinal masses among the
      9263 baseline and 11 126 annual repeat screenings performed in the Early Lung
      Cancer Action Project (ELCAP) and its successor project, the New York ELCAP, were
      identified. Two radiologists confirmed all cases, identified the location and
      measured the diameter (average of length and width) of each mass, and reviewed
      all subsequent CT and clinical and surgical results. The prevalence and incidence
      of mediastinal masses were then determined. RESULTS: Of the 9263 individuals, 71
      had a mediastinal mass seen at baseline screening (prevalence of 0.77%). Of the
      71 masses, 41 were thymic, 16 were thyroidal, two were esophageal cancers, six
      were tracheal-esophageal diverticula, and six were other masses. Among the 11 126
      annual repeat screenings, only one new mediastinal mass was identified (incidence
      of 0.01%). This suggests a long average duration for mediastinal masses in
      asymptomatic people. Among the 41 thymic masses, five were larger than 3.0 cm in
      diameter, and all five were resected; of these five, one was a thymic carcinoma
      and four were noninvasive thymomas. Of the remaining 36 thymic masses, 25 were
      evaluated at follow-up CT 1 year later: Five had increased in diameter, two had
      decreased, and 18 remained unchanged. All 16 thyroid masses were due to goiter;
      none of these were changed at follow-up CT 1 year later. CONCLUSION: Mediastinal
      masses found in the context of CT screening for lung cancer in asymptomatic
      people should be approached in a "conservative" manner; this includes thymic
      masses smaller than 3 cm in diameter, as most of these remain unchanged or even
      decrease in size.

PMID- 16641359
TI  - Case 94: Uterus didelphys with obstructing hemivaginal septum and ipsilateral
      renal agenesis.

PMID- 16641360
TI  - The posterior vertebral scalloping sign.

PMID- 16641361
TI  - Endovascular brachytherapy.

PMID- 16641362
TI  - Diffusion tensor eigenvalues or both mean diffusivity and fractional anisotropy
      are required in quantitative clinical diffusion tensor MR reports: fractional
      anisotropy alone is not sufficient.

PMID- 16641364
TI  - Imaging quantification of infarct size.

PMID- 16641366
TI  - The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA
      transporter required for clearance of synaptic GABA.
AB  - Sodium-dependent neurotransmitter transporters participate in the clearance
      and/or recycling of neurotransmitters from synaptic clefts. The snf-11 gene in
      Caenorhabditis elegans encodes a protein of high similarity to mammalian GABA
      transporters (GATs). We show here that snf-11 encodes a functional GABA
      transporter; SNF-11-mediated GABA transport is Na+ and Cl- dependent, has an EC50
      value of 168 microM, and is blocked by the GAT1 inhibitor SKF89976A. The SNF-11
      protein is expressed in seven GABAergic neurons, several additional neurons in
      the head and retrovesicular ganglion, and three groups of muscle cells.
      Therefore, all GABAergic synapses are associated with either presynaptic or
      postsynaptic (or both) expression of SNF-11. Although a snf-11 null mutation has
      no obvious effects on GABAergic behaviors, it leads to resistance to inhibitors
      of acetylcholinesterase. In vivo, a snf-11 null mutation blocks GABA uptake in at
      least a subset of GABAergic cells; in a cell culture system, all GABA uptake is
      abolished by the snf-11 mutation. We conclude that GABA transport activity is not
      essential for normal GABAergic function in C. elegans and that the localization
      of SNF-11 is consistent with a GABA clearance function rather than recycling.

PMID- 16641368
TI  - Cell aggregation-induced FGF8 elevation is essential for P19 cell neural
      differentiation.
AB  - FGF8, a member of the fibroblast growth factor (FGF) family, has been shown to
      play important roles in different developing systems. Mouse embryonic carcinoma
      P19 cells could be induced by retinoic acid (RA) to differentiate into
      neuroectodermal cell lineages, and this process is cell aggregation dependent. In
      this report, we show that FGF8 expression is transiently up-regulated upon P19
      cell aggregation, and the aggregation-dependent FGF8 elevation is pluripotent
      stem cell related. Overexpressing FGF8 promotes RA-induced monolayer P19 cell
      neural differentiation. Inhibition of FGF8 expression by RNA interference or
      blocking FGF signaling by the FGF receptor inhibitor, SU5402, attenuates neural
      differentiation of the P19 cell. Blocking the bone morphogenetic protein (BMP)
      pathway by overexpressing Smad6 in P19 cells, we also show that FGF signaling
      plays a BMP inhibition-independent role in P19 cell neural differentiation.

PMID- 16641369
TI  - The Caenorhabditis elegans homologue of deleted in azoospermia is involved in the
      sperm/oocyte switch.
AB  - The Deleted in Azoospermia (DAZ) gene family encodes putative translational
      activators that are required for meiosis and other aspects of gametogenesis in
      animals. The single Caenorhabditis elegans homologue of DAZ, daz-1, is an
      essential factor for female meiosis. Here, we show that daz-1 is important for
      the switch from spermatogenesis to oogenesis (the sperm/oocyte switch), which is
      an essential step for the hermaphrodite germline to produce oocytes. RNA
      interference of the daz-1 orthologue in a related nematode, Caenorhabditis
      briggsae, resulted in a complete loss of the sperm/oocyte switch. The C. elegans
      hermaphrodite deficient in daz-1 also revealed a failure in the sperm/oocyte
      switch if the genetic background was conditional masculinization of germline. DAZ
      1 could bind specifically to mRNAs encoding the FBF proteins, which are
      translational regulators for the sperm/oocyte switch and germ stem cell
      proliferation. Expression of the FBF proteins seemed to be lowered in the daz-1
      mutant at the stage for the sperm/oocyte switch. Conversely, a mutation in gld-3,
      a gene that functionally counteracts FBF, could partially restore oogenesis in
      the daz-1 mutant. Together, we propose that daz-1 plays a role upstream of the
      pathway for germ cell sex determination.

PMID- 16641370
TI  - Postreplication repair and PCNA modification in Schizosaccharomyces pombe.
AB  - Ubiquitination of proliferating cell nuclear antigen (PCNA) plays a crucial role
      in regulating replication past DNA damage in eukaryotes, but the detailed
      mechanisms appear to vary in different organisms. We have examined the
      modification of PCNA in Schizosaccharomyces pombe. We find that, in response to
      UV irradiation, PCNA is mono- and poly-ubiquitinated in a manner similar to that
      in Saccharomyces cerevisiae. However in undamaged Schizosaccharomyces pombe
      cells, PCNA is ubiquitinated in S phase, whereas in S. cerevisiae it is
      sumoylated. Furthermore we find that, unlike in S. cerevisiae, mutants defective
      in ubiquitination of PCNA are also sensitive to ionizing radiation, and PCNA is
      ubiquitinated after exposure of cells to ionizing radiation, in a manner similar
      to the response to UV-irradiation. We show that PCNA modification and cell cycle
      checkpoints represent two independent signals in response to DNA damage. Finally,
      we unexpectedly find that PCNA is ubiquitinated in response to DNA damage when
      cells are arrested in G2.

PMID- 16641371
TI  - Multiple sequence elements facilitate Chp Rho GTPase subcellular location,
      membrane association, and transforming activity.
AB  - Cdc42 homologous protein (Chp) is a member of the Rho family of small GTPases and
      shares significant sequence and functional similarity with Cdc42. However, unlike
      classical Rho GTPases, we recently found that Chp depends on palmitoylation,
      rather than prenylation, for association with cellular membranes. Because
      palmitoylation alone is typically not sufficient to promote membrane association,
      we evaluated the possibility that other carboxy-terminal residues facilitate Chp
      subcellular association with membranes. We found that Chp membrane association
      and transforming activity was dependent on the integrity of a stretch of basic
      amino acids in the carboxy terminus of Chp and that the basic amino acids were
      not simply part of a palmitoyl acyltransferase recognition motif. We also
      determined that the 11 carboxy-terminal residues alone were sufficient to promote
      Chp plasma and endomembrane association. Interestingly, stimulation with tumor
      necrosis factor-alpha activated only endomembrane-associated Chp. Finally, we
      found that Chp membrane association was not disrupted by Rho guanine nucleotide
      dissociation inhibitory proteins, which are negative regulators of Cdc42 membrane
      association and biological activity. In summary, the unique carboxy-terminal
      sequence elements that promote Chp subcellular location and function expand the
      complexity of mechanisms by which the cellular functions of Rho GTPases are
      regulated.

PMID- 16641372
TI  - Rab10 regulates membrane transport through early endosomes of polarized Madin
      Darby canine kidney cells.
AB  - Rab10, a protein originally isolated from Madin-Darby Canine Kidney (MDCK)
      epithelial cells, belongs to a family of Rab proteins that includes Rab8 and
      Rab13. Although both Rab8 and Rab13 have been found to mediate polarized membrane
      transport, the function of Rab10 in mammalian cells has not yet been established.
      We have used quantitative confocal microscopy of polarized MDCK cells expressing
      GFP chimeras of wild-type and mutant forms of Rab10 to analyze the function of
      Rab10 in polarized cells. These studies demonstrate that Rab10 is specifically
      associated with the common endosomes of MDCK cells, accessible to endocytic
      probes internalized from either the apical or basolateral plasma membrane
      domains. Expression of mutant Rab10 defective for either GTP hydrolysis or GTP
      binding increased recycling from early compartments on the basolateral endocytic
      pathway without affecting recycling from later compartments or the apical
      recycling pathway. These results suggest that Rab10 mediates transport from
      basolateral sorting endosomes to common endosomes.

PMID- 16641373
TI  - Amino acids regulate retrieval of the yeast general amino acid permease from the
      vacuolar targeting pathway.
AB  - Intracellular sorting of the general amino acid permease (Gap1p) in Saccharomyces
      cerevisiae depends on availability of amino acids such that at low amino acid
      concentrations Gap1p is sorted to the plasma membrane, whereas at high
      concentrations Gap1p is sorted to the vacuole. In a genome-wide screen for
      mutations that affect Gap1p sorting we identified deletions in a subset of
      components of the ESCRT (endosomal sorting complex required for transport)
      complex, which is required for formation of the multivesicular endosome (MVE).
      Gap1p-GFP is delivered to the vacuolar interior by the MVE pathway in wild-type
      cells, but when formation of the MVE is blocked by mutation, Gap1p-GFP
      efficiently cycles from this compartment to the plasma membrane, resulting in
      unusually high permease activity at the cell surface. Importantly, cycling of
      Gap1p-GFP to the plasma membrane is blocked by high amino acid concentrations,
      defining recycling from the endosome as a major step in Gap1p trafficking under
      physiological control. Mutations in LST4 and LST7 genes, previously identified
      for their role in Gap1p sorting, similarly block MVE to plasma membrane
      trafficking of Gap1p. However, mutations in other recycling complexes such as the
      retromer had no significant effect on the intracellular sorting of Gap1p,
      suggesting that Gap1p follows a genetically distinct pathway for recycling. We
      previously found that Gap1p sorting from the Golgi to the endosome requires
      ubiquitination of Gap1p by an Rsp5p ubiquitin ligase complex, but amino acid
      abundance does not appear to significantly alter the accumulation of
      polyubiquitinated Gap1p. Thus the role of ubiquitination appears to be a signal
      for delivery of Gap1p to the MVE, whereas amino acid abundance appears to control
      the cycling of Gap1p from the MVE to the plasma membrane.

PMID- 16641374
TI  - Latency and initiation of the human vestibuloocular reflex to pulsed galvanic
      stimulation.
AB  - Cathodal galvanic currents activate primary vestibular afferents, whereas anodal
      currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to
      determine the latency and initiation of the human vestibuloocular reflex. Three
      dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular
      dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of
      current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal
      subjects. The g-VOR consisted of three components: conjugate torsional eye
      rotation away from cathode toward anode; vertical divergence (skew deviation)
      with hypertropia of the eye on the cathodal and hypotropia of the eye on the
      anodal sides; and conjugate horizontal eye rotation away from cathode toward
      anode. The g-VOR was repeatable across all subjects, its magnitude a linear
      function of the current intensity, its latency about 9.0 ms with GVS of >or=2.5
      mA, and was not suppressed by visual fixation. At 10-mA stimulation, the g-VOR
      [x, y, z] on the cathodal side was [0.77 +/- 0.10, -0.05 +/- 0.05, -0.18 +/- 0.06
      degrees ] (mean +/- 95% confidence intervals) and on the anodal side was [0.79 +/
      0.10, 0.16 +/- 0.05, -0.19 +/- 0.06 degrees ], with a vertical divergence of
      0.20 degrees . Although the horizontal g-VOR could have arisen from activation of
      the horizontal semicircular canal afferents, the vertical-torsional g-VOR
      resembled the vestibuloocular reflex in response to roll-plane head rotation
      about an Earth-horizontal axis and might be a result of both vertical
      semicircular canal and otolith afferent activations. Pulsed GVS is a promising
      technique to investigate latency and initiation of the human vestibuloocular
      reflex because it does not require a large mechanical apparatus nor does it pose
      problems of head inertia or slippage.

PMID- 16641375
TI  - Representation of object size in the somatosensory system.
AB  - In this study we investigate the haptic perception of object size. We report the
      results from four psychophysical experiments. In the first, we ask subjects to
      discriminate the size of objects that vary in surface curvature and compliance
      while changing contact force. We show that objects exhibit size constancy such
      that perception of object size using haptics does not change with changes in
      contact force. Based on these results, we hypothesize that size perception
      depends on the degree of spread between the digits at initial contact with
      objects. In the second experiment, we test this hypothesis by having subjects
      continuously contact an object that changes dynamically in size. We show that
      size perception takes into account the compliance of the object. In the third and
      fourth experiments we attempt to separate the individual contributions of
      proprioceptive and cutaneous input. In the third, we test the ability of subjects
      to perceive object size after altering the sensitivity of cutaneous receptors
      with adapting vibratory stimuli. The results from this experiment suggest that
      initial contact is signaled by the cutaneous slowly adapting type 1 afferents
      (SA1) and/or the rapidly adapting afferents (RA). In the last experiment, we
      block cutaneous input at the site of contact by anesthetizing the digital nerves
      and show that proprioceptive information alone provides only a rough estimate of
      object size. We conclude that the perception of object size depends on inputs
      from SA1 and possibly RA afferents, combined with inputs from proprioceptive
      afferents that signal the spread between digits.

PMID- 16641376
TI  - Reduced excitatory drive in interneurons in an animal model of cortical
      dysplasia.
AB  - Cortical dysplasia (CD) is strongly associated with epilepsy. Enhanced
      excitability in dysplastic neuronal networks is believed to contribute to
      epileptogenesis, but the underlying mechanisms for the hyperexcitability are
      poorly understood. Cortical GABAergic interneurons provide the principal
      inhibition in the neuronal networks by forming inhibitory synapses on excitatory
      neurons. The aim of the present study was to determine if the function of
      interneurons in CD is compromised. In a rat model of CD, in utero irradiation, we
      studied spontaneous and miniature excitatory postsynaptic currents (sEPSCs and
      mEPSCs) in cortical interneurons using whole cell recording techniques. Two types
      of interneurons, type I and type II, were identified based on their distinctive
      spike patterns and short-term synaptic plasticity. We found that the frequencies
      of sEPSCs and mEPSCs were significantly decreased in both types of interneurons
      in CD. However, the amplitude and kinetics of sEPSCs and mEPSCs were not
      different. Five-pulse, 20-Hz stimulation produced short-term depression in type I
      interneurons in both CD and control tissue. Type II interneurons showed a robust
      short-term facilitation in both CD and control tissue. Morphological analysis of
      biocytin-filled neurons revealed that dendritic trees of both types of
      interneurons were not altered in CD. Our results demonstrate that the excitatory
      drive, namely sEPSCs and mEPSCs, in two main types of interneuron is largely
      attenuated in CD, probably due to a reduction in the number of excitatory
      synapses on both types of interneurons in CD.

PMID- 16641377
TI  - Excitatory actions of vasoactive intestinal peptide on mouse thalamocortical
      neurons are mediated by VPAC2 receptors.
AB  - Thalamic nuclei can generate intrathalamic rhythms similar to those observed at
      various arousal levels and pathophysiological conditions such as absence
      epilepsy. These rhythmic activities can be altered by a variety of
      neuromodulators that arise from brain stem regions as well as those that are
      intrinsic to the thalamic circuitry. Vasoactive intestinal peptide (VIP) is a
      neuropeptide localized within the thalamus and strongly attenuates intrathalamic
      rhythms via an unidentified receptor subtype. We have used transgenic mice
      lacking a specific VIP receptor, VPAC(2), to identify its role in VIP-mediated
      actions in the thalamus. VIP strongly attenuated both the slow, 2-4 Hz and
      spindle-like 5-8 Hz rhythmic activities in slices from wild-type mice
      (VPAC(2)(+/+)) but not in slices from VPAC(2) receptor knock-out mice (VPAC(2)(-/
      )), which suggests a major role of VPAC(2) receptors in the antioscillatory
      actions of VIP. Intracellular recordings revealed that VIP depolarized all relay
      neurons tested from VPAC(2)(+/+) mice. In VPAC(2)(-/-) mice, however, VIP
      produced no membrane depolarization in 80% of neurons tested. In relay neurons
      from VPAC(2)+/+ mice, VIP enhanced the hyperpolarization-activated mixed cation
      current, I(h), via cyclic AMP activity, but VIP did not alter I(h) in VPAC(2)-/-
      mice. In VPAC(2)-/- mice, pituitary adenylate cyclase activating-polypeptide
      (PACAP) depolarized the majority of relay neurons via I(h) enhancement presumably
      via PAC(1) receptor activation. Our findings suggest that VIP-mediated actions
      are predominantly mediated by VPAC(2) receptors, but PAC(1) receptors may play a
      minor role. The excitatory actions of VIP and PACAP suggest these peptides may
      not only regulate intrathalamic rhythmic activities, but also may influence
      information transfer through thalamocortical circuits.

PMID- 16641378
TI  - Spike-mediated and graded inhibitory synaptic transmission between leech
      interneurons: evidence for shared release sites.
AB  - Inhibitory synaptic transmission between leech heart interneurons consist of two
      components: graded, gated by Ca2+ entering by low-threshold [low-voltage
      activated (LVA)] Ca channels and spike-mediated, gated by Ca2+ entering by high
      threshold [high-voltage-activated (HVA)] Ca channels. Changes in presynaptic
      background Ca2+ produced by Ca2+ influx through LVA channels modulate spike
      mediated transmission, suggesting LVA channels have access to release sites
      controlled by HVA channels. Here we explore whether spike-mediated and graded
      transmission can use the same release sites and thus how Ca2+ influx by HVA and
      LVA Ca channels might interact to evoke neurotransmitter release. We recorded pre
      and postsynaptic currents from voltage-clamped heart interneurons bathed in 0 mM
      Na+/5 mM Ca2+ saline. Using different stimulating paradigms and inorganic Ca
      channel blockers, we show that strong graded synaptic transmission can occlude
      high-threshold/spike-mediated synaptic transmission when evoked simultaneously.
      Suppression of LVA Ca currents diminishes graded release and concomitantly
      increases the ability of Ca2+ entering by HVA channels to release transmitter.
      Uncaging of Ca chelator corroborates that graded release occludes spike-mediated
      transmission. Our results indicate that both graded and spike-mediated synaptic
      transmission depend on the same readily releasable pool of synaptic vesicles.
      Thus Ca2+, entering cells through different Ca channels (LVA and HVA), acts to
      gate release of the same synaptic vesicles. The data argue for a closer location
      of HVA Ca channels to release sites than LVA Ca channels. The results are
      summarized in a conceptual model of a heart interneuron release site.

PMID- 16641379
TI  - Graded inhibitory synaptic transmission between leech interneurons: assessing the
      roles of two kinetically distinct low-threshold Ca currents.
AB  - In leeches, two pairs of reciprocally inhibitory heart interneurons that form the
      core oscillators of the pattern-generating network for heartbeat possess both
      high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two
      kinetically distinct components (one rapidly activating/inactivating, ICaF, and
      another slowly activating/inactivating, ICaS) that mediate graded transmission,
      generate plateau potentials driving burst formation, and modulate spike-mediated
      transmission between heart interneurons. Here we used different stimulating
      protocols and inorganic Ca channel blockers to separate the effects of ICaF and
      ICaS on graded synaptic transmission and determine their interaction and relative
      efficacy. Ca2+ entering by ICaF channels is more efficacious in mediating release
      than that entering by ICaS channels. The rate of Ca2+ entry by LVA Ca channels
      appears to be as critical as the amount of delivered Ca2+ for synaptic
      transmission. LVA Ca currents and associated graded transmission were selectively
      blocked by 1 mM Ni2+, leaving spike-mediated transmission unaffected.
      Nevertheless, 1 mM Ni2+ affected homosynaptic enhancement of spike-mediated
      transmission that depends on background Ca2+ provided by LVA Ca channels. Ca2+
      provided by both ICaF and ICaS depletes a common pool of readily releasable
      synaptic vesicles. The balance between availability of vesicles and Ca2+
      concentration and its time course determine the strength of inhibitory
      transmission between heart interneurons. We argue that Ca2+ from multichannel
      domains arising from ICaF channels, clustered near but not directly associated
      with the release trigger, and Ca2+ radially diffusing from generally distributed
      ICaS channels interact at common release sites to mediate graded transmission.

PMID- 16641380
TI  - Functional unity of the ponto-cerebellum: evidence that intrapontine
      communication is mediated by a reciprocal loop with the cerebellar nuclei.
AB  - The majority of cerebral signals destined for the cerebellum are handed over by
      the pontine nuclei (PN), which thoroughly reorganize the neocortical topography.
      The PN maps neocortical signals of wide-spread origins into adjacent compartments
      delineated by spatially precise distribution of cortical terminals and
      postsynaptic dendrites. We asked whether and how signals interact on the level of
      the PN. Intracellular fillings of rat PN cells in vitro did not reveal any
      intrinsic axonal branching neither within the range of the cells' dendrites nor
      farther away. Furthermore, double whole cell patch recordings did not show any
      signs of interaction between neighboring pontine cells. Using simultaneous unit
      recording in the PN and cerebellar nuclei (CN) in rats in vivo, we investigated
      whether PN compartments interact via extrinsic reciprocal connections with the
      CN. Repetitive electrical stimulation of the cerebral peduncle of < or = 40 Hz
      readily evoked rapid sequential activation of PN and CN, demonstrating a direct
      connection between the structures. Stimulation of the PN gray matter led to
      responses in neurons < or = 600 microm away from the stimulation site at
      latencies compatible with di- or polysynaptic pathways via the CN. Importantly,
      these interactions were spatially discontinuous around the stimulation electrode
      suggesting that reciprocal PN-CN loops in addition reflect the compartmentalized
      organization of the PN. These findings are in line with the idea that the
      cerebellum makes use of the compartmentalized map in the PN to orchestrate the
      composition of its own neocortical input.

PMID- 16641381
TI  - Dopamine presynaptically depresses fast inhibitory synaptic transmission via D4
      receptor-protein kinase A pathway in the rat dorsolateral septal nucleus.
AB  - The lateral septal nucleus receives a diffuse dopaminergic input originating from
      the ventral tegmental area of the brain stem. We examined whether dopamine (DA)
      modulates synaptic transmission in the slice preparation of the rat dorsolateral
      septal nucleus (DLSN). Bath application (10-15 min) of DA (30 muM) markedly
      depressed the amplitude of fast and slow inhibitory postsynaptic potentials
      (IPSPs) in DLSN neurons, while it produced only a minor depression of the
      amplitude of excitatory postsynaptic potentials (EPSPs) obtained in the presence
      of bicuculline. DA (30 muM) depressed the monosynaptic fast IPSP to approximately
      50% of control, but did not depress the inward current (I(GABA)) induced by
      exogenous gamma-aminobutyric acid (GABA). DA decreased the frequency of miniature
      fast IPSPs (m-fIPSPs) without significantly changing their amplitude. PD 168077,
      a selective D4 receptor agonist, depressed the fast and slow IPSPs but not the
      EPSP and decreased the frequency of m-fIPSPs. Both DA and PD 168077 increased the
      paired-pulse ratio of the monosynaptic fast IPSP. The inhibitory effect of DA on
      the fast IPSP was significantly attenuated by L-741,742, an antagonist at D4
      receptors, but not by SCH 23390 and sulpiride, a D1-like and a D2-like receptor
      antagonist, respectively. N-ethylmaleimide, a blocker of pertussis toxin (PTX)
      sensitive G protein (G(i/o)), attenuated the DA-induced depression of the fast
      IPSP. N-[2-((p-bromocinnamyl) amino)ethyl]-5-isoquinoline sulfonamide, a protein
      kinase A (PKA) inhibitor, attenuated the DA-induced depression of the fast IPSP.
      These results suggest that DA inhibits spontaneous and evoked release of GABA via
      the D4 receptor-G(i)-protein-PKA system in DLSN neurons.

PMID- 16641382
TI  - Discharge properties of monkey tectoreticular neurons.
AB  - The intermediate layers of the superior colliculus (SC) contain neurons that
      clearly play a major role in regulating the production of saccadic eye movements:
      a burst of activity from saccade neurons (SNs) is thought to provide a drive
      signal to set the eyes in motion, whereas the tonic activity of fixation neurons
      (FNs) is thought to suppress saccades during fixation. The exact contribution of
      these neurons to saccade control is, however, unclear because the nature of the
      signals sent by the SC to the brain stem saccade generation circuit has not been
      studied in detail. Here we tested the hypothesis that the SC output signal is
      sufficient to control saccades by examining whether antidromically identified
      tectoreticular neurons (TRNs: 33 SNs and 13 FNs) determine the end of saccades.
      First, TRNs had discharge properties similar to those of nonidentified SC neurons
      and a proportion of output SNs had visually evoked responses, which signify that
      the saccade generator must receive and process visual information. Second, only a
      minority of TRNs possessed the temporal patterns of activity sufficient to
      terminate saccades: Output SNs did not cease discharging at the time of saccade
      end, possibly continuing to drive the brain stem during postsaccadic fixations,
      and output FNs did not resume their activity before saccade end. These results
      argue against a role for SC in regulating the timing of saccade termination by a
      temporal code and suggest that other saccade centers act to thwart the extraneous
      SC drive signal, unless it controls saccade termination by a spatial code.

PMID- 16641383
TI  - Opposite perceptual and sensorimotor responses to a size-weight illusion.
AB  - The perceptual size-weight illusion (SWI) occurs when two different-sized objects
      with equal mass are lifted in sequence: the smaller object is consistently
      reported to feel heavier than the larger object even after repeated lifting
      attempts. Here we explored the relationship between sensorimotor and perceptual
      responses to a SWI in which the smaller of the two target objects in fact weighed
      slightly less (2.7 N) than the larger object (3.2 N). For 20 consecutive lifts,
      participants consistently reported that the small-light object felt heavier than
      the large-heavy object; however, concurrently measured lifting dynamics showed
      exactly the opposite pattern: peak grip force, peak grip force rate, peak load
      force, and peak load force rate were all significantly greater for the large
      heavy object versus the small-light object. The difference in peak load rate
      between the two objects was greatest for the initial lift but decreased
      significantly beyond that point, suggesting that the sensorimotor system used
      sensory feedback to correct for initial over- and underestimations of object
      mass. Despite these adjustments to lifting dynamics over the early trials, the
      difference between the judged heaviness of the two objects did not change. The
      findings clearly demonstrate that the sensorimotor and perceptual systems utilize
      distinctly different mechanisms for determining object mass.

PMID- 16641384
TI  - Scaling of the fore-aft vestibulo-ocular reflex by eye position during smooth
      pursuit.
AB  - An eye position signal scales the amplitude of compensatory eye velocity in the
      translational vestibulo-ocular reflex (TVOR). To investigate the origin of such a
      modulatory signal, we studied the kinematics of the fore-aft TVOR as rhesus
      monkeys pursued a horizontally moving target at velocities between 0.5 and 30
      degrees /s. We found that the "V-shaped" curve of the fore-aft TVOR amplitude as
      a function of eye position was shifted opposite to the direction of pursuit eye
      movement. As a result, the tip of the V-shaped curve that occurred close to zero
      eye position during steady-state fixation was shifted to the right during
      leftward pursuit and to the left during rightward pursuit eye movements. The
      faster the pursuit velocity the larger the observed shift. These results suggest
      that the scaling of the TVOR can precede actual eye position changes by several
      tens of milliseconds, which averaged 169 +/- 87 ms in three rhesus monkeys. Thus,
      central motor commands, rather than low-level efference copy or proprioceptive
      information, may be the signals scaling TVOR amplitude.

PMID- 16641385
TI  - Behavioral and electromyographic characterization of mice lacking EphA4
      receptors.
AB  - EphA4 receptors play an important role in axon guidance during development.
      Disrupting the expression of these receptors in mice has been shown to modify
      neuronal connections in the spinal cord and results in the production of a
      characteristic hopping gait. The EphA4-null mouse has been used in numerous
      investigations aimed at establishing mechanisms responsible for patterning motor
      activity during walking. However, there have been no detailed behavioral or
      electrophysiological studies on adult EphA4-null mice. We used high-speed video
      recordings to determine the coordination of leg movements during locomotion in
      adult EphA4-null mice. Our data show that the hopping movements of the hind legs
      are not always associated with synchronous movements of forelegs. The coupling
      between the forelegs is weak, resulting in changes in their phase relationship
      from step to step. The synchronous coordination of the hind legs can switch to an
      alternating pattern for a short period of time during recovery from isoflurane
      anesthesia. Comparison of the kinematics of hind leg movements in EphA4-null mice
      and wild-type animals shows that besides the synchronous coordination in EphA4
      null mice, the swing durations and the swing amplitude are shorter.
      Electromyographic recordings from a knee extensor muscle show double bursting in
      the EphA4-null animals but single bursts in wild types. This double burst changes
      to single-burst activity during swimming and when hind legs are stepping in
      alternation. These observations suggest an influence of sensory feedback in
      shaping the pattern of muscle activity during locomotion in the mutant animals.
      Our data give the first detailed description of the locomotor behavior of an
      adult mouse with genetically manipulated spinal networks.

PMID- 16641386
TI  - Models and properties of power-law adaptation in neural systems.
AB  - Many biological systems exhibit complex temporal behavior that cannot be
      adequately characterized by a single time constant. This dynamics, observed from
      single channels up to the level of human psychophysics, is often better described
      by power-law rather than exponential dependences on time. We develop and study
      the properties of neural models with scale-invariant, power-law adaptation and
      contrast them with the more commonly studied exponential case. Responses of an
      adapting firing-rate model to constant, pulsed, and oscillating inputs in both
      the power-law and exponential cases are considered. We construct a spiking model
      with power-law adaptation based on a nested cascade of processes and show that it
      can be "programmed" to produce a wide range of time delays. Finally, within a
      network model, we use power-law adaptation to reproduce long-term features of the
      tilt aftereffect.

PMID- 16641387
TI  - Cortical control of a whisking central pattern generator.
AB  - Whether the motor cortex regulates voluntary movements by generating the motor
      pattern directly or by acting through subcortical central pattern generators
      (CPGs) remains a central question in motor control. Using the rat whisker system,
      an important model system of mammalian motor control, we develop an anesthetized
      preparation to investigate the interaction between the motor cortex and a
      whisking CPG. Using this model we investigate the involvement of a serotonergic
      component of the whisking CPG in determining whisking kinematics and the
      mechanisms through which drive from the CPG is converted into movements by
      vibrissa motor units. Consistent with an action of the vibrissa motor cortex
      (vMCx) on a subcortical CPG, the frequency of whisking evoked by intracortical
      microstimulation (ICMS) of vMCx differed significantly from the stimulation
      frequency, whereas whisking onset latencies correlated negatively with
      stimulation intensity. Further, ICMS-evoked whisking was suppressed by a
      serotonin receptor antagonist, supporting previous findings that the whisking CPG
      contains a significant serotonergic component. The amplitude of ICMS-evoked
      whisking was correlated with the number of active motor units-isolated from
      vibrissal EMGs or recorded directly from vibrissa motoneurons-and their activity
      level. In addition, whisking frequency was correlated with the firing rate of
      these motoneurons. These findings support the hypothesis that vMCx regulates
      whisking through its actions on a subcortical CPG.

PMID- 16641388
TI  - Firing patterns of accumbal neurons during a pavlovian-conditioned approach task.
AB  - The nucleus accumbens (NAc) is necessary for the expression of Pavlovian
      conditioned approach behavior but not for the expression of instrumental behavior
      conditioned in sessions that set a low response requirement. Although numerous
      studies have characterized firing patterns of NAc neurons in relation to
      instrumental behavior, very little is known about how NAc neurons encode
      information in Pavlovian tasks. In the present study, recordings of accumbal
      firing patterns were made during sessions in which rats performed a Pavlovian
      conditioned approach task. Most of the recorded neurons (74/83, 89%) exhibited
      significant responses during the conditioned stimulus (CS) presentation and/or
      the reward exposure. The reward responses were prevalent, predominantly
      inhibitory, and comparable to reward responses observed in various types of
      behavioral paradigms, including instrumental tasks. The CS responses could be
      segregated into multiple subtypes on the basis of directionality, onset latency,
      and duration. Several characteristics of the CS firing patterns were unique
      relative to cue responses observed previously during alternative types of
      conditioning sessions. It is possible that the novel firing patterns correspond
      to the differential contributions of the accumbens to Pavlovian-conditioned
      approach behavior and instrumentally conditioned behavior. Regardless, the novel
      patterns of firing add to existing evidence that characterization of accumbal
      firing patterns in Pavlovian tasks may provide additional information about the
      neurophysiological mechanisms that mediate accumbal contributions to behavior.

PMID- 16641389
TI  - Serotonin-immunoreactive CPT interneurons in Hermissenda: identification of
      sensory input and motor projections.
AB  - Serotonin immunoreactive (5-HT-IR) neurons identified as cerebropleural ganglion
      triplets (CPTs) in Hermissenda may be homologues of 5-HT-IR neurons identified in
      other opisthobranch molluscs. In studies of isolated nervous systems and semi
      intact preparations we used a combination of immunohistochemical techniques and
      fluorescent labeling with Lucifer yellow to identify 5-HT-IR CPT neurons after
      investigating sensory inputs and motor neuron projections. Here we show that
      identified 5-HT-IR CPT interneurons receive sensory input from mechanoreceptors
      and photoreceptors. In semi-intact preparations with intact pedal nerves P1 and
      P2, cutaneous stimulation of the middle or tail regions of the foot with
      calibrated von Frey hairs elicited spikes recorded from identified CPT
      interneurons. Illumination of the eyes evoked a small complex excitatory
      postsynaptic potential (EPSP) and resulted in a modest increase in the spike
      discharge of CPT interneurons. Immunostaining of Lucifer yellow-labeled neurons
      revealed that CPT interneurons projected an axonal process to the contralateral
      pedal ganglion. Depolarization of CPT interneurons with extrinsic current evoked
      EPSPs and spikes recorded from identified VP2 pedal neurons, motor neurons
      previously shown to elicit movement of the anterior foot. Extrinsic current
      stimulation of CPT interneurons in semi-intact preparations evoked movement of
      the anterior foot but did not facilitate ciliary activity or evoke PSPs recorded
      in identified VP1 ciliary motor neurons. Our results show that CPT neurons are
      polysensory interneurons that contribute to reflexive foot contractions in
      Hermissenda.

PMID- 16641390
TI  - Videos in clinical medicine. Nasogastric intubation.

PMID- 16641391
TI  - Images in clinical medicine. Cat scratch disease lymphadenopathy.

PMID- 16641392
TI  - The south Asian earthquake six months later--an ongoing crisis.

PMID- 16641393
TI  - The new medical "missionaries"--grooming the next generation of global health
      workers.

PMID- 16641394
TI  - Lung recruitment in patients with the acute respiratory distress syndrome.
AB  - BACKGROUND: In the acute respiratory distress syndrome (ARDS), positive end
      expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping
      lung regions open that otherwise would be collapsed. Since the effects of PEEP
      probably depend on the recruitability of lung tissue, we conducted a study to
      examine the relationship between the percentage of potentially recruitable lung,
      as indicated by computed tomography (CT), and the clinical and physiological
      effects of PEEP. METHODS: Sixty-eight patients with acute lung injury or ARDS
      underwent whole-lung CT during breath-holding sessions at airway pressures of 5,
      15, and 45 cm of water. The percentage of potentially recruitable lung was
      defined as the proportion of lung tissue in which aeration was restored at airway
      pressures between 5 and 45 cm of water. RESULTS: The percentage of potentially
      recruitable lung varied widely in the population, accounting for a mean (+/-SD)
      of 13+/-11 percent of the lung weight, and was highly correlated with the
      percentage of lung tissue in which aeration was maintained after the application
      of PEEP (r2=0.72, P<0.001). On average, 24 percent of the lung could not be
      recruited. Patients with a higher percentage of potentially recruitable lung
      (greater than the median value of 9 percent) had greater total lung weights
      (P<0.001), poorer oxygenation (defined as a ratio of partial pressure of arterial
      oxygen to fraction of inspired oxygen) (P<0.001) and respiratory-system
      compliance (P=0.002), higher levels of dead space (P=0.002), and higher rates of
      death (P=0.02) than patients with a lower percentage of potentially recruitable
      lung. The combined physiological variables predicted, with a sensitivity of 71
      percent and a specificity of 59 percent, whether a patient's proportion of
      potentially recruitable lung was higher or lower than the median. CONCLUSIONS: In
      ARDS, the percentage of potentially recruitable lung is extremely variable and is
      strongly associated with the response to PEEP.

PMID- 16641395
TI  - Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.
AB  - BACKGROUND: Malabsorption of thyroxine has been described in patients treated
      with drugs that modify an acidic environment. We determined whether there is an
      increased need for thyroxine in patients with euthyroid multinodular goiter and
      impaired secretion of gastric acid. METHODS: We assessed the dose of thyroxine
      required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248
      patients with multinodular goiter. Of these 248 patients, 53 also had
      Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body
      of the stomach (31 with evidence of H. pylori infection and 29 without such
      evidence). The reference group comprised 135 patients with multinodular goiter
      and no gastric disorders. In addition, variation in the level of serum
      thyrotropin was prospectively studied in 11 patients treated with thyroxine
      before and after H. pylori infection and both before and during treatment with
      omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux.
      RESULTS: The daily requirement of thyroxine was higher (by 22 to 34 percent) in
      patients with H. pylori-related gastritis, atrophic gastritis, or both conditions
      than in the reference group. In prospective studies, the occurrence of H. pylori
      infection in the 11 patients treated with thyroxine led to an increase in the
      level of serum thyrotropin (P=0.002), an effect that was nearly reversed on
      eradication of H. pylori infection. In a similar way, omeprazole treatment was
      associated with an increase in the level of serum thyrotropin in all 10 patients
      treated with thyroxine, an effect that was reversed by an increase in the
      thyroxine dose by 37 percent. CONCLUSIONS: Patients with impaired acid secretion
      require an increased dose of thyroxine, suggesting that normal gastric acid
      secretion is necessary for effective absorption of oral thyroxine.

PMID- 16641396
TI  - Vitamins C and E and the risks of preeclampsia and perinatal complications.
AB  - BACKGROUND: Supplementation with antioxidant vitamins has been proposed to reduce
      the risk of preeclampsia and perinatal complications, but the effects of this
      intervention are uncertain. METHODS: We conducted a multicenter, randomized trial
      of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to
      daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or
      placebo (microcrystalline cellulose) until delivery. Primary outcomes were the
      risks of maternal preeclampsia, death or serious outcomes in the infants (on the
      basis of definitions used by the Australian and New Zealand Neonatal Network),
      and delivering an infant whose birth weight was below the 10th percentile for
      gestational age. RESULTS: Of the 1877 women enrolled in the study, 935 were
      randomly assigned to the vitamin group and 942 to the placebo group. Baseline
      characteristics of the two groups were similar. There were no significant
      differences between the vitamin and placebo groups in the risk of preeclampsia
      (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent
      confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5
      percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval,
      0.61 to 1.02), or having an infant with a birth weight below the 10th percentile
      for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent
      confidence interval, 0.66 to 1.16). CONCLUSIONS: Supplementation with vitamins C
      and E during pregnancy does not reduce the risk of preeclampsia in nulliparous
      women, the risk of intrauterine growth restriction, or the risk of death or other
      serious outcomes in their infants. (Controlledtrials.com number,
      ISRCTN00416244.).

PMID- 16641397
TI  - Variant of hepatitis B virus with primary resistance to adefovir.
AB  - The reverse-transcriptase inhibitor lamivudine (Zeffix, GlaxoSmithKline) is often
      used to treat chronic infection with hepatitis B virus (HBV) until resistance
      develops. Treatment may then be switched to the reverse-transcriptase inhibitor
      adefovir (Hepsera, Gilead), which has a lower frequency of resistance. Here, we
      describe three cases of primary adefovir resistance that were sensitive to
      tenofovir (Viread, Gilead). All three cases involved a rare HBV variant with a
      valine at position 233 of the reverse-transcriptase domain instead of isoleucine
      (rtI233V), as in the wild-type virus. This HBV variant also displayed resistance
      to adefovir and sensitivity to tenofovir in vitro.

PMID- 16641398
TI  - Hematopoietic stem-cell transplantation.

PMID- 16641399
TI  - Images in clinical medicine. Sudden enlargement of the neck.

PMID- 16641400
TI  - Case records of the Massachusetts General Hospital. Case 13-2006. A 50-year-old
      man with a painful bone mass and lesions in the liver.

PMID- 16641401
TI  - PEEP or no PEEP--lung recruitment may be the solution.

PMID- 16641402
TI  - Antioxidants and the prevention of preeclampsia--unresolved issues.

PMID- 16641403
TI  - Disciplining the stem cell into myogenesis.

PMID- 16641404
TI  - Clozapine alone versus clozapine and risperidone for refractory schizophrenia.

PMID- 16641405
TI  - Hypertonic saline for cystic fibrosis.

PMID- 16641406
TI  - Unprofessional behavior among medical students.

PMID- 16641407
TI  - Illness in returned travelers.

PMID- 16641408
TI  - Preventing nephropathy induced by contrast medium.

PMID- 16641409
TI  - Aspirin to prevent gentamicin-induced hearing loss.

PMID- 16641410
TI  - Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops.

PMID- 16641411
TI  - Evaluation of the larynx for tumour recurrence by diffusion-weighted MRI after
      radiotherapy: initial experience in four cases.
AB  - Radiotherapy-induced changes in the soft tissues of the neck hamper the early
      detection of persistent or recurrent tumour by clinical examination and imaging
      procedures. Diffusion-weighted (DW) MRI is a non-invasive technique capable of
      probing tissue properties by measuring the movement of water. The purpose of the
      ongoing study is to examine the usefulness of DW-MRI for differentiation of
      persistent or recurrent tumour from post-radiotherapeutic sequelae or
      complications. Four patients, suspected of tumour recurrence after radiotherapy
      for laryngeal squamous cell carcinoma, were examined using a DW-MRI sequence on a
      clinical 1.5 T MR system prior to surgery. In two patients, the DW-MRI images
      showed an asymmetric hyperintense lesion on b1000 images with low apparent
      diffusion coefficient (ADC)-value, compatible with tumour on histopathology. All
      surrounding tissue presented high ADC values and absent signal on the b1000
      images, histopathologically correlating to post-radiotherapeutic changes. The
      images of the third and fourth patient showed absent or minimal symmetric
      hyperintensity of the laryngeal soft tissues on the b1000 images and high ADC
      values. In these cases, the histopathological diagnosis of radionecrosis was made
      and no tumour was found. In all four cases, differentiation of tumoral tissue
      from radiotherapy-induced tissue alterations was possible with DW-MRI.

PMID- 16641412
TI  - CT of thoracic lymph nodes. Part II: diseases and pitfalls.
AB  - CT is the primary non-invasive technique for the diagnostic evaluation of
      thoracic lymph nodes. The CT patterns and anatomic location of thoracic lymph
      node involvement can provide important clues in the diagnosis of many diseases.
      Part I of the pictorial review illustrates the anatomic location and drainage of
      thoracic lymph nodes in the chest wall, mediastinum, and lungs through examples
      of pathologic involvement. Part II of the pictorial review focuses on CT patterns
      of lymph node involvement in various pulmonary and extrapulmonary diseases,
      differential diagnoses based on CT findings, and pitfalls.

PMID- 16641413
TI  - Nurse-led central venous catheter service: Christie experience.
AB  - The aim of this study was to evaluate the success and complication rate of Nurse
      led subclavian central venous catheter (CVC) insertion using the landmark
      technique. A prospective study was performed on all subclavian CVC insertion
      between 13/01/03 to 01/07/03. Data recorded included indication for catheter
      insertion, type of catheter, complications during the procedure and patient
      satisfaction. A total of 348 subclavian cuffed tunnelled catheters were inserted
      over the study period. The age group ranged from 31 years to 84 years with a mean
      age of 53 years. This included 192 women and 156 men. The majority of CVC
      insertions were through the right subclavian (79%) and were single lumen (76%).
      In total, complications were encountered in 48 patients (14%). These included
      misplaced tip in 29 (8%), arterial puncture in 16 (4%), pneumothorax in 3 (1%)
      and the procedure failed in 3 (1%). Of these multiple complications were seen in
      3 (1%). No interventions were required for the pneumothoraces or for the arterial
      punctures. In conclusion, nurse-led subclavian CVC placements using the landmark
      technique are both safe and effective.

PMID- 16641414
TI  - Occupational exposure in the electrophysiology laboratory: quantifying and
      minimizing radiation burden.
AB  - Fluoroscopically guided procedures in the electrophysiology room, such as
      radiofrequency catheter ablation and implantation of cardiac resynchronization
      devices, may result in high radiation exposure of electrophysiologists and
      assisting staff. Our aim was to provide accurate and applicable data on
      occupational doses to the electrophysiology laboratory personnel. We exposed
      fluoroscopically an anthropomorphic phantom at three projections common in
      electrophysiology studies. For each exposure, scattered radiation was measured at
      182 sites of the cardiology room at four body levels. Effective dose values, eye
      lens, skin and gonadal doses to the laboratory staff were calculated. Our study
      has shown that a procedure requiring 40 min of fluoroscopy yields a maximum
      effective dose of 129 microSv and a maximum value of gonadal dose of 56.8 microSv
      to staff using a 0.35 mm lead-equivalent apron. A conservative estimate of the
      electrophysiologist's annual maximum permissible workload is 155 procedures.
      Staff effective dose values vary by a factor of 40 due to positioning during
      fluoroscopy and by a factor of 11 due to radiation protection equipment.
      Undercouch protective shields may reduce gonadal doses up to 98% and effective
      dose up to 25%. Consequently, radiation levels in the electrophysiology room are
      not negligible. Mitigation of occupational exposure is feasible through good
      fluoroscopy and working practices.

PMID- 16641415
TI  - Ultrasound spectrum in intraductal papillary neoplasms of breast.
AB  - Intraductal papillary neoplasms (IPNs) of breast form a wide spectrum of
      pathological changes with benign intraductal papilloma occupying one end of the
      spectrum and papillary carcinoma at the other end. Intraductal papillomas are
      known to occur anywhere within the ductal system and are broadly classified into
      central and peripheral types. Intraductal papillary carcinoma is an uncommon
      ductal malignancy forming papillary structures, and these lesions
      characteristically lack the myoepithelial layer present in benign papillary
      neoplasms. Three basic patterns of IPNs are recognized on ultrasound -
      intraductal mass with or without ductal dilatation, intracystic mass and a
      predominantly solid pattern with the intraductal mass totally filling the duct.
      Benign papillomas are known to exhibit calcifications which tend to be extremely
      dense and coarse. IPNs are highly vascular tumours and have a propensity to bleed
      spontaneously. A distinct vascular pedicle is identified within the central core
      of IPNs, with branching vessels arborising within the mass. In an older age
      group, presence of a large solid component and evidence of spontaneous
      intracystic bleed are more suggestive of papillary carcinomas than benign
      papillomas. We have serially studied 42 cases of intraductal papillary neoplasms
      with sonomammography and mammography from 2001 to 2004.

PMID- 16641416
TI  - Improved motion compensation in 3D-CT using respiratory-correlated segment
      reconstruction: diagnostic and radiotherapy applications.
AB  - Conventional respiratory-gated CT and four-dimensional CT (4DCT) are
      disadvantaged by their low temporal resolution, which results in the inclusion of
      anatomic motion-induced artefacts. These represent a significant source of error
      both in radiotherapy treatment planning for the thorax and upper abdomen and in
      diagnostic procedures. In particular, temporal resolution and image quality are
      vitally important to accurate diagnosis and the minimization of planning target
      volume margin due to respiratory motion. To improve both temporal resolution and
      signal-to-noise ratio (SNR), we developed a respiratory-correlated segment
      reconstruction method (RS) and adapted it to the Feldkamp-Davis-Kress algorithm
      (FDK) with a 256 multidetector row CT (256MDCT). The 256MDCT scans approximately
      100 mm in the craniocaudal direction with a 0.5 mm slice thickness in one
      rotation. Data acquisition for the RS-FDK relies on the assistance of a
      respiratory sensing system operating in cine scan mode (continuous axial scan
      with the table stationary). We evaluated the RS-FDK for volume accuracy and image
      noise in a phantom study with the 256MDCT and compared results with those for a
      full scan (FS-FDK), which is usually employed in conventional 4DCT and in half
      scan (HS-FDK). Results showed that the RS-FDK gave a more accurate volume than
      the others and had the same SNR as the FS-FDK. In a subsequent animal study, we
      demonstrated a practical sorting process for projection data which was unaffected
      by variations in respiratory period, and found that the RS-FDK gave the clearest
      visualization among the three algorithms of the margins of the liver and
      pulmonary vessels. In summary, the RS-FDK algorithm provides multi-phase images
      with higher temporal resolution and better SNR. This method should prove useful
      when combined with new radiotherapeutic and diagnostic techniques.

PMID- 16641417
TI  - In vitro evaluation of stent patency and in-stent stenoses in 10 metallic stents
      using MR angiography.
AB  - In vitro study to investigate the suitability of contrast enhanced magnetic
      resonance angiography (CEMRA) for determination of stent patency and grading of
      in-stent stenoses in 10 metallic stents. The Acculink carotid, DynaLink, Easy
      Wallstent, JostentSelfX XF, Luminexx, Omnilink, sinus-SuperFlex, SMART, Symphony
      and ZA stent were separately placed in a vascular phantom. Dedicated stenoses
      inside the stents generated a concentric lumen narrowing of 50%. CEMRA was
      performed for each stent. Signal loss inside the stents and artificial lumen
      narrowing were assessed objectively using the evaluation software of the MR
      imager. Moreover, three blinded observers determined visibility of stent patency
      and in-stent stenoses subjectively on a 3-point scale and graded in-stent
      stenoses. Loss of signal intensity within the stent lumen ranged between 90%
      (Wallstent) and 5% (ZA), artificial lumen narrowing between 56% (Symphony) and
      22% (ZA). For the Symphony and Wallstent, visibility of patency and in-stent
      stenoses was impaired and the observers' grading exaggerated the degree of
      stenoses (by 23% and 33%, respectively). For the remainder of stents, patency and
      stenoses were visible and stenoses were graded accurately (less than 10%
      discrepancy from reference standard). In this in vitro study, eight of 10 stents
      presented with MRI characteristics which enabled determination of stent patency
      and accurate grading of clinically relevant in-stent stenoses.

PMID- 16641418
TI  - Feasibility of automated matching of supine and prone CT-colonography
      examinations.
AB  - Matching of prone and supine positions in CT colonography may improve accuracy of
      polyp detection. The purpose of this study was to investigate the feasibility of
      automatic prone-supine matching in CT-colonography using proven polyps as fixed
      points of reference. The method is based on similarities in the direction of
      centre-lines and allows for compression and extraction of the centre-lines in
      both positions. To illustrate the impact of the match error of the new method in
      practice, the visibility of the matched polyps in a primary three-dimensional
      unfolded cube setting was determined as well. The method was compared with a
      method that relies on the normalized distance along the centre-line (NDAC
      method). The median absolute match error was 14 mm (range 0-59 mm, average 20 mm)
      either proximal or distal from the actual polyp in prone position. In the
      observer study, 70% (26/37) of the polyps were directly visible in prone view.
      The overall difference in median absolute match error between both methods was
      small (2 mm), although half way along the centre-line there were polyps with
      substantial differences in match error (larger with NDAC). We concluded that
      automated prone-supine matching of CT-colonography studies is feasible and has a
      low match error. The difference with the NDAC method was small and not
      significant, although half way along the centre-line some differences were seen.

PMID- 16641419
TI  - CT of thoracic lymph nodes. Part I: anatomy and drainage.
AB  - CT is the primary non-invasive technique for the diagnostic evaluation of
      thoracic lymph nodes. The CT patterns and anatomic location of thoracic lymph
      node involvement can provide important clues in the diagnosis of many diseases.
      Part I of the pictorial review illustrates the anatomic location and drainage of
      thoracic lymph nodes in the chest wall, mediastinum and lungs through examples of
      pathologic involvement. Part II of the pictorial review focuses on CT patterns of
      lymph node involvement in various pulmonary and extrapulmonary diseases,
      differential diagnoses based on CT findings and pitfalls.

PMID- 16641420
TI  - Usefulness of diffusion/perfusion-weighted MRI in patients with non-enhancing
      supratentorial brain gliomas: a valuable tool to predict tumour grading?
AB  - 22 patients with non-enhancing supratentorial gliomas on contrast-enhanced MRI
      underwent both diffusion- and perfusion-weighted MRI (DWI/PWI) before surgical
      resection. 14 low-grade gliomas (WHO Grade I and II) and 8 anaplastic gliomas
      were verified histologically. Both apparent diffusion coefficient (ADC) values
      and relative cerebral blood volume (rCBV) ratios were calculated on the solid
      portion of the tumour, on peritumoural area, as well as on the contralateral
      normal white matter, respectively. The results showed that lower ADC values were
      present in the solid portions of anaplastic gliomas, but not in low grade (p <
      0.01). All ADC values in peritumoural regions of tumours were decreased compared
      with the contralateral normal white matter. However, there was no significant
      difference between anaplastic gliomas and low-grade gliomas. Meanwhile, higher
      rCBV ratios were present in both solid portions and peritumoural regions of
      anaplastic gliomas, but not in low grade gliomas (p < 0.01). In conclusion, non
      enhancing brain gliomas with lower ADC values in the solid portions and higher
      rCBV ratios in both solid portions and peritumoural regions of tumours are
      significantly correlated with anaplasia. Therefore, DWI and PWI should be
      integrated in the diagnostic work-up of non-enhancing gliomas in order to predict
      grading.

PMID- 16641422
TI  - Optimizing localization accuracy in head and neck, and brain radiotherapy.
AB  - The purpose of this study was to investigate the impact on localization of
      utilizing contrast-enhanced CT scans and the formal input of a radiologist in the
      planning process. 25 head and neck/brain patients had pre- and post-contrast CT
      scans in the treatment position. Radiotherapy treatment was planned on the
      unenhanced CT images as per standard practice. Retrospectively, their scans
      (unenhanced and enhanced) were re-contoured by two oncologists and a radiologist.
      These new contours were compared with the original unenhanced treatment contours
      and differences in contour volume, geographical isocentre position and tolerance
      coverage of the associated planning target volumes (PTVs) were evaluated using
      the original plans. The use of contrast enhanced CT data during localization by
      the oncologist shows little change in gross tumour volumes (GTVs) or PTVs,
      geographical position or tolerance coverage for the targets in the brain studied
      here. Larger changes in mean volume are seen for the head and neck cases alone.
      Changes are greater and statistically significant (p < 0.05, Wilcoxon signed rank
      test) for localization by the radiologist. Furthermore, when comparing the
      original PTV marked by the oncologist with a new PTV re-contoured by the
      oncologist, but based on a GTV marked-up by the radiologist, again statistically
      significant (p < 0.01) changes in percentage volume are noted. Intraoperator
      precision is good, percentage volume differences being of the order 3-6%. PTVs
      also show improved standard deviations compared with GTVs. Geographic shifts are
      generally within our departmental tolerance levels for daily patient setup.
      Comparing precision of unenhanced data with enhanced, mean percentage volume
      changes are smaller, but not statistically significant. The use of enhanced scan
      data for localization has little effect on size, geographical position or
      tolerance coverage of PTVs marked up by the oncologists in this study. However,
      more important is the input from a radiologist. Statistically significant
      differences due to mark-up on enhanced scans by the radiologist are shown.
      Furthermore, significant differences are also seen between PTVs based on
      oncologist-generated GTVs, and those based on radiologist-generated GTVs.

PMID- 16641423
TI  - Imaging well-differentiated hepatocellular carcinoma with dynamic triple-phase
      helical computed tomography.
AB  - To investigate the imaging appearance of well-differentiated hepatocellular
      carcinoma (HCC) on dynamic CT, a total of 38 histopathologically proven well
      differentiated HCC were included in a retrospective study. We reviewed the
      contrast-enhanced dynamic CT of all 38 tumours for attenuation of each tumour in
      unenhanced scan, arterial-dominant and delayed portal venous phases. Our results
      showed that dynamic CT identified 26 (68.4%) out of the 38 lesions. The remaining
      12 lesions were isodense compared with surrounding liver parenchyma in each
      dynamic CT phase. There was no statistically significant difference between the
      mean size of tumours detected by dynamic CT and that of tumours not detected by
      dynamic CT (p = 0.1). Of a total of 38 tumours, most were isodense (n = 19) or
      hypodense (n = 16) in unenhanced scan, mostly hyperdense (n = 18) or isodense (n
      = 15) in arterial-dominant phase and mostly isodense (n = 22) or hypodense (n =
      15) in delayed portal venous phase. Enhancement of tumour was observed in 19
      (50.0%) of 38 lesions. In conclusion, the ability of dynamic CT to detect well
      differentiated HCC is poor, and negative CT findings cannot exclude the presence
      of well-differentiated HCC, especially if there is well-grounded clinical
      suspicion for HCC.

PMID- 16641424
TI  - Cognitive rehabilitation for schizophrenia and the putative role of motivation
      and expectancies.
AB  - Cognitive rehabilitation (CR) approaches seek to enhance cognitive processes or
      to circumvent cognitive impairments in schizophrenia in an effort to improve
      functional outcome. In this review we examine the research findings on the 8
      evidence-based approaches to cognitive remediation listed in the 2005 Training
      Grid Outlining Best Practices for Recovery and Improved Outcomes for People With
      Serious Mental Illness, developed by the American Psychological Association
      Committee for the Advancement of Professional Practice. Though the approaches
      vary widely in theoretical orientation and methods of intervention, the results
      are, for the most part, encouraging. Improvements in attention, memory, and
      executive functioning have been reported. However, many persons with
      schizophrenia are more impaired in real-world functioning than one would expect
      given the magnitude of their cognitive deficits. We may need to look beyond
      cognition to other targets such as motivation to identify the reasons that many
      persons with schizophrenia demonstrate such marked levels of disability. Although
      a number of current CR approaches address motivation to varying degrees, treating
      motivation as a primary target may be needed to maximize CR outcomes.

PMID- 16641426
TI  - Polyamines induce resistance to cationic peptide, aminoglycoside, and quinolone
      antibiotics in Pseudomonas aeruginosa PAO1.
AB  - Pseudomonas aeruginosa, a gram-negative bacterium of human pathogens, is noted
      for its environmental versatility, enormous metabolic capacity, and resistance to
      antibiotics. Overexpression of the outer membrane protein OprH and increased
      resistance to polycationic peptide antibiotics (e.g., polymyxin B) mediated by
      the PhoPQ two-component system on induction of a putative lipopolysaccharide
      (LPS) modification operon (PA3552-PA3559) have been reported as part of the
      adaptive responses to magnesium limitation in P. aeruginosa. Induction of the
      oprH-phoPQ operon and the LPS modification operon by exogenous spermidine was
      revealed from GeneChip analysis during studies of polyamine metabolism and was
      confirmed by the lacZ fusions of affected promoters. From the results of MIC
      measurements, it was found that addition of spermidine or other polyamines to the
      growth medium increased the MIC values of multiple antibiotics, including
      polycationic antibiotics, aminoglycosides, quinolones, and fluorescent dyes. MIC
      values of these compounds in the transposon insertion mutants of oprH, phoP,
      phoQ, and pmrB were also determined in the presence and absence of spermidine.
      The results showed that the spermidine effect on cationic peptide antibiotic and
      quinolone resistance was diminished in the phoP mutant only. The spermidine
      effect on antibiotics was not influenced by magnesium concentrations, as
      demonstrated by MICs and oprH::lacZ fusion studies in the presence of 20 muM or 2
      mM magnesium. Furthermore, in spermidine uptake mutants, MICs of cationic peptide
      antibiotics and fluorescent dyes, but not of aminoglycosides and quinolones, were
      increased by spermidine. These results suggested the presence of a complicated
      molecular mechanism for polyamine-mediated resistance to multiple antibiotics in
      P. aeruginosa.

PMID- 16641427
TI  - Polyamines increase antibiotic susceptibility in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen. Treatment is
      complicated by frequent acquired resistance to antipseudomonal therapies.
      Polyamines (cadaverine, putrescine, spermidine, and spermine) are ubiquitous
      polycationic compounds essential for all living organisms. In a dose-dependent
      manner, polyamines increased the susceptibility of P. aeruginosa to 14 beta
      lactam antibiotics, chloramphenicol, nalidixic acid, and trimethoprim as
      demonstrated by a reduction in MIC of up to 64-fold. This effect was partially
      antagonized (25 to 50%) by the presence of 10 mM of Mg(2+) or Ca(2+). In
      contrast, the effects of the outer membrane permeabilizers, polymyxin B
      nonapeptide and EDTA, were completely abolished by 3 mM Mg(2+) or Ca(2+). Changes
      on the outer membrane barrier by these compounds were assessed by activity
      measurements of periplasmic beta-lactamase. The results showed that while EDTA
      and polymyxin B serve as outer membrane disorganizing agents as expected,
      exogenous spermidine and spermine did not exhibit any apparent effect on outer
      membrane permeability or rupture. In summary, these results strongly suggest that
      the increased antibiotic susceptibility by polyamines is exerted by a mechanism
      that differs from that of EDTA and polymyxin B. Polyamines might be potentially
      useful in antipseudomonal therapies by increasing the effectiveness of certain
      beta-lactam antibiotics.

PMID- 16641428
TI  - Pharmacodynamics of levofloxacin against Pseudomonas aeruginosa with reduced
      susceptibility due to different efflux pumps: do elevated MICs always predict
      reduced in vivo efficacy?
AB  - The Pseudomonas aeruginosa efflux pumps MexAB-OprM, MexCD-OprJ, and MexEF-OprN
      play an important role in susceptibility to fluoroquinolones in vitro. To
      determine if levofloxacin MICs arising from different levels of expression of
      efflux pumps result in a proportional reduction in the response to levofloxacin
      in vivo, isogenic strains of P. aeruginosa were tested with levofloxacin in two
      mouse models of infection (sepsis and neutropenic mouse thigh models). The
      levofloxacin 50% effective doses (ED(50)s) increased proportionally with the MICs
      for most strains. Similarly, the 24-h area under the concentration-time curve
      (AUC)/MIC ratio that resulted in 90% of the maximum bactericidal activity (90%
      E(max)) exceeded 75 for all strains except those with elevated MICs due to MexEF
      OprN overexpression. In these strains, levofloxacin ED(50)s were 2- to 10-fold
      lower than the ED(50)/MIC ratios in the other strains and 90% E(max) AUC/MIC
      ratios were 2- to 4-fold lower than those predicted from pharmacodynamic modeling
      of efficacy against other strains. These data show that while the MexEF-OprN
      efflux pump can provide P. aeruginosa resistance to levofloxacin in vitro, it
      appears to be less efficient in providing resistance to levofloxacin in animal
      models of infection.

PMID- 16641429
TI  - Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of
      Pseudomonas aeruginosa clinical isolates.
AB  - Carbapenems are important agents for the therapy of infections due to multidrug
      resistant Pseudomonas aeruginosa; the development of carbapenem resistance
      hampers effective therapeutic options. To assess the mechanisms leading to
      resistance, 33 clinical isolates with differing degrees of carbapenem
      susceptibility were analyzed for the expression of the chromosomal beta-lactamase
      (ampC), the porin that is important for the entry of carbapenems (oprD), and the
      proteins involved in four efflux systems (mexA, mexC, mexE, and mexX). Real-time
      reverse transcriptase PCR was performed using primers and fluorescent probes for
      each of the target genes. The sequencing of regulatory genes (ampR, mexR, nalC,
      nalD, mexT, and mexZ) was also performed. Diminished expression of oprD was
      present in all imipenem- and meropenem-resistant isolates but was not required
      for ertapenem resistance. Increased expression of ampC was not observed in
      several isolates that were overtly resistant to carbapenems. Increased expression
      of several efflux systems was observed in many of the carbapenem-resistant
      isolates. Increased efflux activity correlated with high-level ertapenem
      resistance and reduced susceptibility to meropenem and aztreonam. Most isolates
      with increased expression of mexA had mutations affecting nalC and/or nalD. Two
      isolates with mutations leading to a premature stop codon in mexZ had markedly
      elevated mexX expressions, although mutations in mexZ were not a prerequisite for
      overexpression. beta-Lactam resistance in clinical isolates of P. aeruginosa is a
      result of the interplay between diminished production of oprD, increased activity
      of ampC, and several efflux systems.

PMID- 16641430
TI  - Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC
      alone in treatment of chronic hepatitis B.
AB  - Emtricitabine (FTC) is approved for the treatment of human immunodeficiency
      virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV).
      This report summarizes the results of a double-blind, multicenter study of
      patients with chronic hepatitis B who had completed a phase 3 study of FTC and
      were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC
      QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three
      patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were
      men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen
      positive, and the median baseline HBV DNA level was 6 log(10) copies/ml. After 24
      weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels
      of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four
      weeks posttreatment, the mean change in serum HBV DNA levels from baseline was 
      1.25 log(10) copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for
      FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for
      FTC alone) (P < or = 0.025 for all endpoints). The safety profile was similar
      between arms during treatment, with less posttreatment exacerbation of hepatitis
      B in the combination arm. In summary, after 24 weeks of treatment, no significant
      difference between arms was observed, but there was a significantly greater
      virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm.

PMID- 16641431
TI  - New potential antimalarial agents: therapeutic-index evaluation of
      pyrroloquinazolinediamine and its prodrugs in a rat model of severe malaria.
AB  - Tetra-acetamide pyrroloquinazolinediamine (PQD-A4) and bis-ethylcarbamyl
      pyrroloquinazolinediamine (PQD-BE) are new derivatives of
      pyrroloquinazolinediamine (PQD) and are being investigated as potential
      chemotherapeutic agents for the treatment of malaria. Comparative studies to
      assess the therapeutic indices of PQD-A4, PQD-BE, and PQD were conducted in
      Plasmodium berghei-infected rats following daily intragastric dosing for three
      consecutive days. Artesunate (AS), a standard drug for treatment of severe
      malaria, was used as a comparator. The minimum doses required to clear malaria
      parasitemia were 156 micromol/kg of body weight for AS and 2.4 micromol/kg for
      PQD, PQD-4A, and PQD-BE. The maximum tolerated dose (MTD) of AS was 625
      micromol/kg, and its therapeutic index was calculated to be 4. The MTDs of PQD
      A4, PQD-BE, and PQD were found to be 190, 77, and 24 micromol/kg, respectively,
      yielding therapeutic indices of 80, 32, and 10, respectively. Although PQD-A4 and
      PQD-BE are only half as potent as PQD based on their curative effects, the two
      new derivatives, PQD-4A and PQD-BE, are 8.0-fold and 3.2-fold safer,
      respectively, than their parent compound when they are dosed for three
      consecutive days. Oral PQD-A4 and PQD-BE are 44 to 70 times more potent on an mg
      basis than intravenous AS. As assessed from the therapeutic index over 3 days,
      PQD-A4, PQD-BE, and PQD administered orally are 20.0, 8.0, and 2.5 times safer
      than AS given intravenously. The results indicate that PQD-4A is a promising
      candidate for antimalarial treatment.

PMID- 16641432
TI  - Proteomic study of peptide deformylase inhibition in Streptococcus pneumoniae and
      Staphylococcus aureus.
AB  - Peptide deformylase (PDF) is an essential enzyme in both gram-negative and gram
      positive bacteria. It hydrolyzes formylated N-terminal peptides to generate free
      N-terminal peptides during the process of protein maturation. Inhibition of this
      enzyme results in cessation of bacterial growth. We have examined the effect of a
      potent PDF inhibitor, LBM-415 (also known as VIC-104959), on the proteomes of
      Staphylococcus aureus and Streptococcus pneumoniae using two-dimensional
      electrophoresis. Both S. aureus and S. pneumoniae showed accumulation of many N
      terminal formylated peptides/proteins upon PDF inhibition. In S. pneumoniae,
      formylated peptide/protein accumulation was time dependent. Following inhibition,
      subsequent removal of the inhibitor resulted in deformylation of formylated
      peptides/proteins; this recovery process was also time dependent. If instead the
      inhibited cells were maintained in the presence of sub-MIC levels of the PDF
      inhibitor, the formylated peptides/proteins remained for a much longer time,
      which correlated with a prolonged postantibiotic effect in vitro. These
      observations may have broader implications for the application of this class of
      antibiotics in vivo.

PMID- 16641433
TI  - Calcium signals are affected by ciprofloxacin as a consequence of reduction of
      mitochondrial DNA content in Jurkat cells.
AB  - The effects of ciprofloxacin on mitochondrial DNA (mtDNA) content, oxygen
      consumption, mitochondrial membrane potential, cellular ATP formation, and
      capacitative Ca(2+) entry into Jurkat cells were investigated. In cells incubated
      for several days with 25 mug/ml ciprofloxacin, a 60% reduction of mtDNA content,
      inhibition of the respiratory chain, and a significant decrease in mitochondrial
      membrane potential were observed. These changes led to a decrease in the calcium
      buffering capacity of mitochondria which, in turn, resulted in a gradual
      inhibition of the capacitative Ca(2+) entry. On days 4, 7, and 11 of incubation
      with ciprofloxacin, the initial rates of Ca(2+) entry were reduced by 33%, 50%,
      and 50%, respectively. Ciprofloxacin caused a transient decrease in the cellular
      capability for ATP formation. In cells incubated for 15 min with glucose,
      pyruvate, and glutamine as exogenous fuel, ciprofloxacin reduced ATP content by
      16% and 35% on days 4 and 7, respectively, of incubation with the drug. However,
      on day 11 of incubation with ciprofloxacin, a recovery of cellular ATP formation
      was observed. In conclusion, long-term exposure of Jurkat cells to ciprofloxacin
      at a concentration of 25 mug/ml seriously affects cellular energy metabolism and
      calcium homeostasis.

PMID- 16641434
TI  - LL-37 protects rats against lethal sepsis caused by gram-negative bacteria.
AB  - We investigated the efficacy of LL-37, the C-terminal part of the only
      cathelicidin in humans identified to date (termed human cationic antimicrobial
      protein), in three experimental rat models of gram-negative sepsis. Adult male
      Wistar rats (i) were given an intraperitoneal injection of 1 mg Escherichia coli
      0111:B4 LPS, (ii) were given 2 x 10(10) CFU of Escherichia coli ATCC 25922, or
      (iii) had intra-abdominal sepsis induced via cecal ligation and puncture. For
      each model, all animals were randomized to receive intravenously isotonic sodium
      chloride solution, 1-mg/kg LL-37, 1-mg/kg polymyxin B, 20-mg/kg imipenem, or 60
      mg/kg piperacillin. Lethality; growth of bacteria in blood, peritoneum, spleen,
      liver, and mesenteric lymph nodes; and endotoxin and tumor necrosis factor alpha
      (TNF-alpha) concentrations in plasma were evaluated. All compounds reduced
      lethality compared to levels in controls. Endotoxin and TNF-alpha plasma levels
      were significantly higher in conventional antibiotic-treated rats than in LL-37-
      and polymyxin B-treated animals. All drugs tested significantly reduced bacterial
      growth compared to saline treatment. No statistically significant differences
      between LL-37 and polymyxin B were noted for antimicrobial and antiendotoxin
      activities. LL-37 and imipenem proved to be the most effective treatments in
      reducing all variables measured. Due to its multifunctional properties, LL-37 may
      become an important future consideration for the treatment of sepsis.

PMID- 16641435
TI  - Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa
      PAO1: a global approach.
AB  - The administration of macrolides such as azithromycin for chronic pulmonary
      infection of cystic fibrosis patients has been reported to be of benefit.
      Although the mechanisms of action remain obscure, anti-inflammatory effects as
      well as interference of the macrolide with Pseudomonas aeruginosa virulence
      factor production have been suggested to contribute to an improved clinical
      outcome. In this study we used a systematic approach and analyzed the impact of
      azithromycin on the global transcriptional pattern and the protein expression
      profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The
      most remarkable result of this study is the finding that azithromycin exhibited
      extensive quorum-sensing antagonistic activities. In accordance with the
      inhibition of the quorum-sensing systems, virulence factor production was
      diminished and the oxidative stress response was impaired, whereas the type III
      secretion system was strongly induced. Moreover, P. aeruginosa motility was
      reduced, which probably accounts for the previously observed impaired biofilm
      formation capabilities of azithromycin-treated cultures. The interference of
      azithromycin with quorum-sensing-dependent virulence factor production, biofilm
      formation, and oxidative stress resistance in P. aeruginosa holds great promise
      for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist
      macrolides should be paid more attention in the management of chronic P.
      aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain
      vital importance for more general application against chronic infections.

PMID- 16641436
TI  - Cellular accumulation and activity of quinolones in ciprofloxacin-resistant J774
      macrophages.
AB  - Ciprofloxacin is the substrate for a multidrug resistance-related protein (MRP)
      like multidrug transporter in J774 mouse macrophages, which also modestly affects
      levofloxacin but only marginally affects garenoxacin and moxifloxacin (J.-M.
      Michot et al., Antimicrob. Agents Chemother. 49:2429-2437, 2005). Two clones of
      ciprofloxacin-resistant cells were obtained by a stepwise increase in drug
      concentration (from 34 to 51 to 68 mg/liter) in the culture fluid. Compared to
      wild-type cells, ciprofloxacin-resistant cells showed (i) a markedly reduced
      ciprofloxacin accumulation (12% of control) and (ii) a two- to threefold lower
      sensitivity to the enhancing effect exerted by MRP-inhibitors (probenecid and
      MK571) on ciprofloxacin accumulation or by ciprofloxacin itself. ATP-depletion
      brought ciprofloxacin accumulation to similarly high levels in both wild-type and
      ciprofloxacin-resistant cells. Garenoxacin and moxifloxacin accumulation remained
      unaffected, and levofloxacin showed an intermediate behavior. DNA and protein
      synthesis were not impaired in ciprofloxacin-resistant cells for ciprofloxacin
      concentrations up to 100 mg/liter (approximately 85 and 55% inhibition,
      respectively, in wild-type cells). In Listeria monocytogenes-infected
      ciprofloxacin-resistant cells, 12-fold higher extracellular concentrations of
      ciprofloxacin were needed to show a bacteriostatic effect in comparison with wild
      type cells. The data suggest that the resistance mechanism is mediated by an
      overexpression and/or increased activity of the MRP-like ciprofloxacin
      transporter expressed at a basal level in wild-type J774 macrophages, which
      modulates both the intracellular pharmacokinetics and activity of ciprofloxacin.

PMID- 16641437
TI  - Preclinical safety and efficacy assessments of dendrimer-based (SPL7013)
      microbicide gel formulations in a nonhuman primate model.
AB  - Three gel formulations (1%, 3%, and 5% [wt/wt]) of SPL7013, a dendrimer known to
      have antiviral (anti-human immunodeficiency virus and anti-herpes simplex virus)
      activities, completed a range of preclinical tests in the pigtailed macaque
      models for vaginally and rectally applied topical microbicide safety assessments.
      The vaginal safety profile of the 3% SPL7013 gel formulation was equal to that of
      the 1% formulation but was superior to that of the 5% formulation. The 3% SPL7013
      gel was further evaluated for rectal safety and for antichlamydial efficacy with
      cervical challenge with Chlamydia trachomatis. This first-generation dendrimer
      based product was shown to be safe to the vaginal and rectal microenvironments
      with repeated daily use. However, a single intravaginal application of the 3%
      (wt/wt) SPL7013 gel did not provide protection from the acquisition of cervical
      chlamydial infection.

PMID- 16641438
TI  - 7-O-malonyl macrolactin A, a new macrolactin antibiotic from Bacillus subtilis
      active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant
      enterococci, and a small-colony variant of Burkholderia cepacia.
AB  - We report here the discovery, isolation, and chemical and preliminary biological
      characterization of a new antibiotic compound, 7-O-malonyl macrolactin A (MMA),
      produced by a Bacillus subtilis soil isolate. MMA is a bacteriostatic antibiotic
      that inhibits a number of multidrug-resistant gram-positive bacterial pathogens,
      including methicillin-resistant Staphylococcus aureus, vancomycin-resistant
      enterococci, and a small-colony variant of Burkholderia cepacia. MMA-treated
      staphylococci and enterococci were pseudomulticellular and exhibited multiple
      asymmetric initiation points of septum formation, indicating that MMA may inhibit
      a cell division function.

PMID- 16641439
TI  - Antifungal activity of C-27 steroidal saponins.
AB  - As part of our search for new antifungal agents from natural resources, 22 C-27
      steroidal saponins and 6 steroidal sapogenins isolated from several
      monocotyledonous plants were tested for their antifungal activity against the
      opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei,
      Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the
      antifungal activity of the steroidal saponins was associated with their aglycone
      moieties and the number and structure of monosaccharide units in their sugar
      chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4)
      with a sugar moiety of four or five monosaccharide units exhibited significant
      activity against C. neoformans and A. fumigatus, comparable to the positive
      control amphotericin B. The antifungal potency of these compounds was not
      associated with cytotoxicity to mammalian cells. This suggests that the C-27
      steroidal saponins may be considered potential antifungal leads for further
      preclinical study.

PMID- 16641440
TI  - Predictors of mortality in patients with bloodstream infection due to ceftazidime
      resistant Klebsiella pneumoniae.
AB  - Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated
      with high rates of morbidity and mortality. The aim of this study was to identify
      predictors of in-hospital mortality among patients with BSI due to ceftazidime
      resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center.
      Patients with CAZ-R K. pneumoniae BSI were identified by our microbiology
      laboratory between January 1995 and June 2003. Clinical data were collected
      retrospectively. Logistic regression was used to identify independent predictors
      of all causes of in-hospital mortality. Of 779 patients with K. pneumoniae BSI,
      60 (7.7%) had BSI due to CAZ-R K. pneumoniae; 43 (72%) of these were nosocomial
      infections. Pulsed-field gel electrophoresis identified a single predominant
      strain in 17 (28%) patients. The in-hospital mortality rate was 43% (n = 26).
      Among patients with CAZ-R K. pneumoniae BSI, those who died were similar to
      survivors with respect to demographic, clinical, and antimicrobial susceptibility
      characteristics. Only 43 (72%) patients received effective therapy within 5 days
      of BSI. In bivariable analysis, delay in initiation of effective therapy for >72
      h after diagnosis of BSI was associated with death (P = 0.03). Strain genotype
      was not predictive of outcome. In multivariable analysis, delay in initiation of
      effective therapy for >72 h after diagnosis of BSI was an independent predictor
      of death (odds ratio, 3.32; 95% confidence interval, 1.07 to 10.3). Thus, among
      patients with BSI due to CAZ-R K. pneumoniae, a delay in the initiation of
      effective therapy of greater than 72 h after BSI was associated with a >3-fold
      increase in mortality risk.

PMID- 16641441
TI  - Pharmacokinetics of telbivudine in subjects with various degrees of hepatic
      impairment.
AB  - This study evaluated the effect of hepatic impairment on the pharmacokinetics of
      telbivudine, an investigational nucleoside antiviral for the treatment of chronic
      hepatitis B virus infection. Twenty-four subjects were assigned to four hepatic
      function groups (normal function and mild, moderate, and severe impairment, with
      six subjects in each group) on the basis of Child-Pugh scores. The subjects were
      administered a single oral dose of 600 mg telbivudine, and blood samples were
      collected over a 48-h interval for pharmacokinetic analyses. Telbivudine was well
      tolerated by all subjects. Telbivudine plasma concentration-time profiles were
      similar across the four hepatic function groups. The principal pharmacokinetic
      parameters of drug exposure, i.e., the maximum plasma concentration and area
      under the drug concentration-time curve, were comparable between subjects with
      various degrees of hepatic impairment and those with normal hepatic function.
      Results from this single-dose pharmacokinetic assessment therefore provide a
      pharmacologic rationale for further evaluation of the safety and efficacy of
      telbivudine in hepatitis B virus-infected patients with decompensated liver
      diseases.

PMID- 16641442
TI  - Activity of retapamulin against Streptococcus pyogenes and Staphylococcus aureus
      evaluated by agar dilution, microdilution, E-test, and disk diffusion
      methodologies.
AB  - The in vitro activity of retapamulin against 106 Staphylococcus aureus isolates
      and 109 Streptococcus pyogenes isolates was evaluated by the agar dilution, broth
      microdilution, E-test, and disk diffusion methodologies. Where possible, the
      tests were performed by using the CLSI methodology. The results of agar dilution,
      broth microdilution, and E-test (all with incubation in ambient air) for S.
      aureus yielded similar MICs, in the range of 0.03 to 0.25 microg/ml. These values
      corresponded to zone diameters between 25 and 33 mm by the use of a 2-microg
      retapamulin disk. Overall, 99% of the agar dilution results and 95% of E-test
      results for S. aureus were within +/-1 dilution of the microdilution results. For
      S. pyogenes, the MICs obtained by the agar and broth microdilution methods (both
      after incubation in ambient air) were in the range of 0.008 to 0.03 microg/ml,
      and E-test MICs (with incubation in ambient air) were 0.016 to 0.06 microg/ml.
      For S. pyogenes, 100% of the agar dilution MIC results were within +/-1 dilution
      of the broth microdilution results. E-test MICs (after incubation in ambient air)
      were within +/-1 and +/-2 dilutions of the broth microdilution results for 76%
      and 99% of the isolates, respectively. E-test MICs for S. pyogenes strains in
      CO(2) were up to 4 dilutions higher than those in ambient air. Therefore, it is
      recommended that when retapamulin MICs are determined by E-test, incubation be
      done in ambient air and not in CO(2), due to the adverse effect of CO(2) on the
      activity of this compound. Diffusion zones (with incubation in CO(2)) for S.
      pyogenes were 18 to 24 mm. Retapamulin MICs for all strains by all methods (with
      incubation in ambient air) were < or =0.25 microg/ml. These results demonstrate
      that S. pyogenes (including macrolide-resistant strains) and S. aureus (including
      methicillin-resistant and vancomycin-nonsusceptible strains) are inhibited by
      very low concentrations of retapamulin and that all four testing methods are
      satisfactory for use for susceptibility testing.

PMID- 16641443
TI  - Antimalarial activity of allicin, a biologically active compound from garlic
      cloves.
AB  - The incidence of malaria is increasing, and there is an urgent need to identify
      new drug targets for both prophylaxis and chemotherapy. Potential new drug
      targets include Plasmodium proteases that play critical roles in the parasite
      life cycle. We have previously shown that the major surface protein of Plasmodium
      sporozoites, the circumsporozoite protein (CSP), is proteolytically processed by
      a parasite-derived cysteine protease, and this processing event is temporally
      associated with sporozoite invasion of host cells. E-64, a cysteine protease
      inhibitor, inhibits CSP processing and prevents invasion of host cells in vitro
      and in vivo. Here we tested allicin, a cysteine protease inhibitor found in
      garlic extracts, for its ability to inhibit malaria infection. At low
      concentrations, allicin was not toxic to either sporozoites or mammalian cells.
      At these concentrations, allicin inhibited CSP processing and prevented
      sporozoite invasion of host cells in vitro. In vivo, mice injected with allicin
      had decreased Plasmodium infections compared to controls. When sporozoites were
      treated with allicin before injection into mice, malaria infection was completely
      prevented. We also tested allicin on erythrocytic stages and found that a 4-day
      regimen of allicin administered either orally or intravenously significantly
      decreased parasitemias and increased the survival of infected mice by 10 days.
      Together, these experiments demonstrate that the same cysteine protease inhibitor
      can target two different life cycle stages in the vertebrate host.

PMID- 16641444
TI  - Clarithromycin delays progression of bronchial epithelial cells from G1 phase to
      S phase and delays cell growth via extracellular signal-regulated protein kinase
      suppression.
AB  - The nonsteroidal anti-inflammatory drugs have been shown to support
      cytoprotection of cells by shifting cells toward a quiescent state (G(0)/G(1)).
      Extracellular signal-regulated kinase (ERK) is required for cells to pass from
      G(1) phase into S phase, and macrolide antibiotics can inhibit ERK1/2
      phosphorylation. However, previous reports suggest that macrolide antibiotics do
      not affect cell growth in bronchial epithelial cells. Therefore, we studied
      normal human bronchial epithelial (NHBE) cells to determine whether
      clarithromycin (CAM) suppresses ERK, delays bronchial epithelial cells from
      progressing to S phase, and delays cell growth. Exposure to CAM at 10 microg/ml
      daily over 4 days irreversibly decreased the cell proliferation with and without
      growth supplements (P < 0.0001). CAM also inhibited ERK1/2 phosphorylation over
      the first 90 min of exposure (P < 0.05 for 30 min, P < 0.0001 for 60 min, and P <
      0.01 for 90 min) and decreased the ratio of phosphorylated ERK1/2 (pERK1/2) to
      total ERK1/2 (tERK1/2) (P < 0.0001). Incubation with CAM for 48 h increased the
      proportion of cells in G(1) phase (means +/- standard deviations) from 63.5% +/-
      0.9% to 79.1% +/- 1.4% (P < 0.0001), decreased that in S phase from 19.8% +/-
      1.2% to 10.0% +/- 2.1% (P < 0.01), and decreased that in G(2)/M phase from 16.7%
      +/- 0.4% to 11.0% +/- 0.8% (P < 0.001). In contrast, the ratio of pMEK1/2 to
      tMEK1/2 was not altered after exposure to CAM. These results suggest that
      macrolide antibiotics can delay the progression of NHBE cells from G(1) phase to
      S phase and can slow cell growth, probably through the suppression of ERK1/2.

PMID- 16641445
TI  - Complex genetic structures with repeated elements, a sul-type class 1 integron,
      and the blaVEB extended-spectrum beta-lactamase gene.
AB  - Two clinical isolates of Pseudomonas aeruginosa, TL-1 and TL-2, were isolated
      from a patient transferred from Bangladesh and hospitalized for osteomyelitis in
      Paris, France. P. aeruginosa TL-1 expressed the extended-spectrum beta-lactamase
      VEB-1a and was susceptible only to imipenem and colistin, while P. aeruginosa TL
      2 expressed only the naturally occurring bla(AmpC) gene at a basal level and
      exhibited a wild-type beta-lactam resistance phenotype. In TL-1, the typical 5'
      end conserved sequence (5'-CS) region of class 1 integrons usually present
      upstream of the bla(VEB-1a) gene was replaced by a truncated 3'-CS and a 135-bp
      repeated element (Re). Downstream of the bla(VEB-1a) gene, an insertion sequence,
      ISPa31 disrupted by ISPa30, and an orf513 sequence, belonging to a common region
      (conserved region 1 [CR1]) immediately upstream of the aphA-6 gene, were present.
      Further downstream, a second truncated 3'-CS region in direct repeat belonged to
      In51, an integron containing two gene cassettes (aadA6 and the OrfD cassette).
      Thus, the overall structure corresponded to a sul-type class 1 integron termed
      In121. Genetic analyses revealed that both isolates were clonally related and
      differed by a ca. 100-kb fragment that contained In121. Both isolates contained
      another integron, In122, that carried three gene cassettes: aadB, dfrA1, and the
      OrfX cassette. This work identifies for the first time the spread of Re
      associated bla(VEB) genes located on a sul-type integron. It also reports for the
      first time a CR1 element in P. aeruginosa that is associated with an
      aminoglycoside resistance aphA-6 gene that is expressed from a composite
      promoter.

PMID- 16641446
TI  - Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires
      nisin resistance.
AB  - Nisin, a posttranslationally modified antimicrobial peptide produced by
      Lactococcus lactis, is widely used as a food preservative. Yet, the mechanisms
      leading to the development of nisin resistance in bacteria are poorly understood.
      We used whole-genome DNA microarrays of L. lactis IL1403 to identify the factors
      underlying acquired nisin resistance mechanisms. The transcriptomes of L. lactis
      IL1403 and L. lactis IL1403 Nis(r), which reached a 75-fold higher nisin
      resistance level, were compared. Differential expression was observed in genes
      encoding proteins that are involved in cell wall biosynthesis, energy metabolism,
      fatty acid and phospholipid metabolism, regulatory functions, and metal and/or
      peptide transport and binding. These results were further substantiated by
      showing that several knockout and overexpression mutants of these genes had
      strongly altered nisin resistance levels and that some knockout strains could no
      longer become resistant to the same level of nisin as that of the wild-type
      strain. The acquired nisin resistance mechanism in L. lactis is complex,
      involving various different mechanisms. The four major mechanisms are (i)
      preventing nisin from reaching the cytoplasmic membrane, (ii) reducing the
      acidity of the extracellular medium, thereby stimulating the binding of nisin to
      the cell wall, (iii) preventing the insertion of nisin into the membrane, and
      (iv) possibly transporting nisin across the membrane or extruding nisin out of
      the membrane.

PMID- 16641447
TI  - Clinical and bacteriological efficacy in treatment of acute exacerbations of
      chronic bronchitis with cefditoren-pivoxil versus cefuroxime-axetil.
AB  - A randomized, double-blind, double-dummy trial was performed comparing 200 mg of
      cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil
      treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute
      exacerbations of chronic bronchitis. The modified intention-to-treat population
      included 541 patients. Patients were assessed during therapy, at the end of
      therapy (visit 3; primary evaluation time point), and at follow-up. Clinical
      success was obtained in 79.9% of the 264 patients included in the cefditoren
      pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group
      (treatment difference, 95% confidence interval [CI]: -2.8, -9.7 to 3.6%).
      Treatment clinical effects were more clearly seen in sputum signs (decreasing
      volume and purulence from approximately 80% to approximately 10% of the
      patients). At the end of treatment, exploratory analysis of the per-pathogen
      bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil
      arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment
      difference; 95% CI: 5.8, -7.0 to 18.6%). Globally, the per-pathogen
      bacteriological response correlated well with clinical success: 83.5% of 164
      baseline isolates from patients with a clinical success were eradicated or
      presumably eradicated, in contrast to only 3% of 33 isolates from patients with a
      clinical failure. Clinical success in patients infected with Haemophilus
      influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40)
      (treatment difference; 95% CI: 1.5, -14 to 17%) in the cefditoren-pivoxil versus
      the cefuroxime-axetil group. Although this study does not prove that either drug
      is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime
      axetil course had similar point estimates of success in acute exacerbations of
      chronic bronchitis.

PMID- 16641448
TI  - Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah
      virus infection.
AB  - Clinical nonrandomized trials demonstrate some efficacy for ribavirin in the
      treatment of patients with severe Nipah virus-induced encephalitis. We report
      here that EICAR, the 5-ethynyl analogue of ribavirin, and the OMP-decarboxylase
      inhibitors 6-aza-uridine and pyrazofurin have strong antiviral activity against
      Nipah virus replication in vitro. Ribavirin and 6-aza-uridine were tested further
      in hamsters infected with a lethal dose of Nipah virus. The activity of these
      small-molecule inhibitors was compared with that of the interferon inducer
      poly(I)-poly(C(12)U). Both ribavirin and 6-aza-uridine were able to delay but not
      prevent Nipah virus-induced mortality. Poly(I)-poly(C(12)U), at 3 mg/kg of body
      weight daily from the day of infection to 10 days postinfection, prevented
      mortality in 5 of 6 infected animals.

PMID- 16641449
TI  - Long-term multiple-dose pharmacokinetics of human monoclonal antibodies (MAbs)
      against human immunodeficiency virus type 1 envelope gp120 (MAb 2G12) and gp41
      (MAbs 4E10 and 2F5).
AB  - While certain antibodies directed against the human immunodeficiency virus (HIV)
      envelope have the potential to suppress virus replication in vitro, the impact of
      neutralizing antibodies in vivo remains unclear. In a recent proof-of-concept
      study, the broadly neutralizing monoclonal antibodies 2G12, 4E10, and 2F5
      exhibited inhibitory activities in vivo, as exemplified by a delay of the viral
      rebound following the interruption of antiretroviral therapy. Unexpectedly, the
      antiviral effect seen was most prominently due to 2G12 activity. To further
      investigate whether differential HIV-inhibitory activity was due to different
      pharmacokinetic properties of the antibodies, we performed a formal
      pharmacokinetic analysis with 14 patients. Repeated infusions at high dose levels
      were well tolerated by the patients and did not elicit an endogenous immune
      response against the monoclonal antibodies. The pharmacokinetic parameters of all
      three antibodies correlated with each other. Mean estimates were 0.047, 0.035,
      and 0.044 liter/kg for the central volume of distribution of 2G12, 4E10, and 2F5,
      respectively, and 0.0018, 0.0058, and 0.0077 liter/kg . day for the systemic
      clearance of 2G12, 4E10, and 2F5, respectively. Monoclonal antibody 2G12 had a
      significantly longer elimination half-life (21.8 +/- 7.2 days [P < 0.0001]) than
      monoclonal antibodies 4E10 (5.5 +/- 2.2 days) and 2F5 (4.3 +/- 1.1 days). The
      comprehensive pharmacokinetic data from this long-term multiple-dose phase II
      study were coherent with those from previous short-term phase I studies, as
      assessed by compartmental and noncompartmental techniques. The anti-HIV type 1
      antibodies studied showed distribution and elimination kinetics similar to those
      seen for other human-like antibodies. Further studies examining tissue
      concentrations to explain the differential in vivo activity of the anti-gp120
      antibody compared with those of the two anti-gp41 antibodies are warranted.

PMID- 16641450
TI  - Stepwise upregulation of the Pseudomonas aeruginosa chromosomal cephalosporinase
      conferring high-level beta-lactam resistance involves three AmpD homologues.
AB  - Development of resistance to the antipseudomonal penicillins and cephalosporins
      mediated by hyperproduction of the chromosomal cephalosporinase AmpC is a major
      threat to the successful treatment of Pseudomonas aeruginosa infections. Although
      ampD inactivation has been previously found to lead to a partially derepressed
      phenotype characterized by increased AmpC production but retaining further
      inducibility, the regulation of ampC in P. aeruginosa is far from well
      understood. We demonstrate that ampC expression is coordinately repressed by
      three AmpD homologues, including the previously described protein AmpD plus two
      additional proteins, designated AmpDh2 and AmpDh3. The three AmpD homologues are
      responsible for a stepwise ampC upregulation mechanism ultimately leading to
      constitutive hyperexpression of the chromosomal cephalosporinase and high-level
      antipseudomonal beta-lactam resistance, as shown by analysis of the three single
      ampD mutants, the three double ampD mutants, and the triple ampD mutant. This is
      achieved by a three-step escalating mechanism rendering four relevant expression
      states: basal-level inducible expression (wild type), moderate-level
      hyperinducible expression with increased antipseudomonal beta-lactam resistance
      (ampD mutant), high-level hyperinducible expression with high-level beta-lactam
      resistance (ampD ampDh3 double mutant), and very high-level (more than 1,000-fold
      compared to the wild type) derepressed expression (triple mutant). Although one
      step inducible-derepressed expression models are frequent in natural resistance
      mechanisms, this is the first characterized example in which expression of a
      resistance gene can be sequentially amplified through multiple steps of
      derepression.

PMID- 16641451
TI  - Sodium antimony gluconate induces generation of reactive oxygen species and
      nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase
      activation in Leishmania donovani-infected macrophages.
AB  - Pentavalent antimony complexes, such as sodium stibogluconate and sodium antimony
      gluconate (SAG), are still the first choice for chemotherapy against various
      forms of leishmaniasis, including visceral leishmaniasis, or kala-azar. Although
      the requirement of a somewhat functional immune system for the antileishmanial
      action of antimony was reported previously, the cellular and molecular mechanism
      of action of SAG was not clear. Herein, we show that SAG induces extracellular
      signal-regulated kinase 1 (ERK-1) and ERK-2 phosphorylation through
      phosphoinositide 3-kinase (PI3K), protein kinase C, and Ras activation and p38
      mitogen-activated protein kinase (MAPK) phosphorylation through PI3K and Akt
      activation. ERK-1 and ERK-2 activation results in an increase in the production
      of reactive oxygen species (ROS) 3 to 6 h after SAG treatment, while p38 MAPK
      activation and subsequent tumor necrosis factor alpha release result in the
      production of nitric oxide (NO) 24 h after SAG treatment. Thus, this study has
      provided the first evidence that SAG treatment induces activation of some
      important components of the intracellular signaling pathway, which results in an
      early wave of ROS-dependent parasite killing and a stronger late wave of NO
      dependent parasite killing. This opens up the possibility of this metalloid
      chelate being used in the treatment of various diseases either alone or in
      combination with other drugs and vaccines.

PMID- 16641452
TI  - Minocycline impedes African trypanosome invasion of the brain in a murine model.
AB  - Passage of Trypanosoma brucei across the blood-brain barrier (BBB) is a hallmark
      of late-stage human African trypanosomiasis. In the present study we found that
      daily administration of minocycline, a tetracycline antibiotic, impedes the
      penetration of leukocytes and trypanosomes into the brain parenchyma of T. brucei
      brucei-infected C57BL/6 mice. The trypanosome-induced astrocytic and microglial
      reactions were reduced in the minocycline-treated mice, as were the levels in the
      brain of transcripts encoding adhesion molecules intercellular adhesion molecule
      1 (ICAM-1) and endothelial-leukocyte adhesion molecule 1 (E-selectin); the
      inflammatory cytokines tumor necrosis factor alpha, interleukin-1alpha (IL
      1alpha), IL-1beta, IL-6, and gamma interferon; and matrix metalloprotease 3 (MMP
      3), MMP-8, and MMP-12. Loss of weight occurring during infection with T. b.
      brucei was not observed after treatment of the mice with minocycline; these mice
      also survived longer than nontreated mice. Invasion of trypanosomes and
      leukocytes into the brain parenchyma most likely triggered the loss of weight and
      death of infected animals, since minocycline did not affect the growth of T. b.
      brucei either in vitro or in vivo or the levels of the transcripts encoding the
      cytokines and MMPs in the spleen. In conclusion, our data show that T. b. brucei
      invasion of the brain is related to that of leukocytes and that minocycline can
      ameliorate the disease in trypanosome-infected mice.

PMID- 16641453
TI  - Novel effects of azithromycin on tight junction proteins in human airway
      epithelia.
AB  - The macrolide antibiotic azithromycin improves lung function and prognosis among
      patients with cystic fibrosis or diffuse panbronchiolitis, independently of
      bacterial eradication. Anti-inflammatory effects have been implicated, but data
      from in vivo studies are scarce, and the link between abnormal electrolyte
      content in airway surface liquid and bronchial infections remains uncertain. In
      the present study, we treated human airway epithelia on filter supports with
      azithromycin and monitored transepithelial electrical resistance. We found that
      azithromycin increased transepithelial electrical resistance of airway epithelia
      in a dose-dependent manner. Immunocytochemistry and Western blotting showed that
      addition of azithromycin changed the locations of proteins in cell cultures and
      induced processing of the tight junction proteins claudin-1 and claudin-4,
      occludin, and junctional adhesion molecule-A. These effects were reversible, and
      no effect was seen when cells were treated with penicillin or erythromycin. The
      data indicate that azithromycin increases the transepithelial electrical
      resistance of human airway epithelia by changing the processing of tight junction
      proteins. The results are novel and may help explain the beneficial effects of
      azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and
      community-acquired pneumonia.

PMID- 16641454
TI  - VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits
      potent antiviral activities in HCv replicon cells.
AB  - The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral
      replication and therefore has been one of the most attractive targets for
      developing specific antiviral agents against HCV. VX-950, a highly selective,
      reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is
      currently in clinical development for the treatment of hepatitis C. In this
      report, we describe the in vitro characterization of anti-HCV activities of VX
      950 in subgenomic HCV replicon cells. Incubation with VX-950 resulted in a time-
      and dose-dependent reduction of HCV RNA and proteins in replicon cells. Moreover,
      following a 2-week incubation with VX-950, a reduction in HCV RNA levels of 4.7
      log(10) was observed, and this reduction resulted in elimination of HCV RNA from
      replicon cells, since there was no rebound in replicon RNA after withdrawal of
      the inhibitor. The combination of VX-950 and alpha interferon was additive to
      moderately synergistic in reducing HCV RNA in replicon cells with no significant
      increase in cytotoxicity. The benefit of the combination was sustained over time:
      a 4-log(10) reduction in HCV RNA level was achieved following a 9-day incubation
      with VX-950 and alpha interferon at lower concentrations than when either VX-950
      or alpha interferon was used alone. The combination of VX-950 and alpha
      interferon also suppressed the emergence of in vitro resistance mutations against
      VX-950 in replicon cells.

PMID- 16641455
TI  - EDTA as an adjunct antifungal agent for invasive pulmonary aspergillosis in a
      rodent model.
AB  - Rats immunosuppressed by the administration of cyclophosphamide and cortisone
      acetate and then infected with Aspergillus fumigatus were treated with an
      antifungal drug, EDTA, or a combination of one of the antifungal agents,
      amphotericin B lipid complex (ABLC; 5 mg/kg of body weight/day for 7 days), and
      EDTA (30 mg/kg/day for 7 days). The mortality rate was reduced, the duration of
      survival was increased, fewer A. fumigatus organisms were recovered from the
      lungs, and less-severe lung lesions were seen histopathologically in the rats
      receiving the combination treatment than in the rats receiving either an
      antifungal agent or EDTA alone. Further studies regarding the mechanisms of EDTA
      and its interactions with ABLC are warranted, and further studies are needed to
      more fully examine the safety, tolerance, and optimal dosing of EDTA in the
      treatment of this and other fungal infections.

PMID- 16641456
TI  - Photoinactivation of Mycobacteria in vitro and in a new murine model of localized
      Mycobacterium bovis BCG-induced granulomatous infection.
AB  - Treatment of tuberculosis is currently hindered by prolonged antibiotic regimens
      and the emergence of significant drug resistance. Alternatives and adjuncts to
      standard antimycobacterial agents are needed. We propose that a direct attack
      utilizing photosensitizers and light-based treatments may be effective in
      curtailing Mycobacterium tuberculosis in discrete anatomical sites in the most
      infectious phase of pulmonary tuberculosis. To demonstrate experimental proof of
      principle, we have applied established photodynamic therapy (PDT) technology to
      in vitro cultures and an in vivo mouse model using Mycobacterium bovis BCG. We
      report here in vitro and in vivo PDT efficacy studies and the use of a three
      dimensional collagen gel as a delivery vehicle for BCG, subcutaneously inserted,
      to induce specifically localized granuloma-like lesions in mice. When a
      benzoporphyrin derivative was utilized as the photosensitive agent, exposure to
      light killed extracellular and intracellular BCG in significant numbers. Collagen
      scaffolds containing BCG inserted in situ in BALB/c mice for 3 months mimicked
      granulomatous lesions and demonstrated a marked cellular infiltration upon
      histological examination, with evidence of caseating necrosis and fibrous capsule
      formation. When 10(5) BCG were present in the in vivo-induced granulomas, a
      significant reduction in viable mycobacterial cells was demonstrated in PDT
      treated granulomas compared to those of controls. We conclude that PDT has
      potential in the treatment of localized mycobacterial infections, such as
      pulmonary granulomas and cavities.

PMID- 16641457
TI  - Antibiofilm activity of GlmU enzyme inhibitors against catheter-associated
      uropathogens.
AB  - The colonization of uropathogenic bacteria on urinary catheters resulting in
      biofilm formation frequently leads to the infection of surrounding tissue and
      often requires removal of the catheter. Infections associated with biofilms are
      difficult to treat since they may be more than 1,000 times more resistant to
      antibiotics than their planktonic counterparts. We have developed an antibiofilm
      composition comprising an N-acetyl-D-glucosamine-1-phosphate acetyltransferase
      (GlmU) inhibitor and protamine sulfate, a cationic polypeptide. The antibiofilm
      activity of GlmU inhibitors, such as iodoacetamide (IDA), N-ethyl maleimide
      (NEM), and NEM analogs, including N-phenyl maleimide, N,N'-(1,2
      phenylene)dimaleimide (oPDM), and N-(1-pyrenyl)maleimide (PyrM), was tested
      against that of catheter-associated uropathogens. Both IDA and NEM inhibited
      biofilm formation in Escherichia coli. All NEM analogs showed antibiofilm
      activity against clinical isolates of E. coli, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Staphylococcus epidermidis, and Enterococcus faecalis. The
      combination of oPDM with protamine sulfate (PS) enhanced its antibiofilm activity
      and reduced its effective concentration to as low as 12.5 microM. In addition, we
      found that the in vitro inhibitory activity of oPDM-plus-PS-coated silicone
      catheters against P. aeruginosa and S. epidermidis colonization was superior to
      that of catheters coated with silver hydrogel. Confocal scanning laser microscopy
      further confirmed that the oPDM-plus-PS-coated silicone catheters were almost
      free from bacterial colonization. Thus, a broad-spectrum antibiofilm composition
      comprising a GlmU inhibitor and protamine sulfate shows promise for use in anti
      infective coatings for medical devices, including urinary catheters.

PMID- 16641458
TI  - Functional characterization and target validation of alternative complex I of
      Plasmodium falciparum mitochondria.
AB  - This study reports on the first characterization of the alternative
      NADH:dehydrogenase (also known as alternative complex I or type II
      NADH:dehydrogenase) of the human malaria parasite Plasmodium falciparum, known as
      PfNDH2. PfNDH2 was shown to actively oxidize NADH in the presence of quinone
      electron acceptors CoQ(1) and decylubiquinone with an apparent K(m) for NADH of
      approximately 17 and 5 muM, respectively. The inhibitory profile of PfNDH2
      revealed that the enzyme activity was insensitive to rotenone, consistent with
      recent genomic data indicating the absence of the canonical NADH:dehydrogenase
      enzyme. PfNDH2 activity was sensitive to diphenylene iodonium chloride and
      diphenyl iodonium chloride, known inhibitors of alternative NADH:dehydrogenases.
      Spatiotemporal confocal imaging of parasite mitochondria revealed that loss of
      PfNDH2 function provoked a collapse of mitochondrial transmembrane potential
      (Psi(m)), leading to parasite death. As with other alternative
      NADH:dehydrogenases, PfNDH2 lacks transmembrane domains in its protein structure,
      and therefore, it is proposed that this enzyme is not directly involved in
      mitochondrial transmembrane proton pumping. Rather, the enzyme provides reducing
      equivalents for downstream proton-pumping enzyme complexes. As inhibition of
      PfNDH2 leads to a depolarization of mitochondrial Psi(m), this enzyme is likely
      to be a critical component of the electron transport chain (ETC). This notion is
      further supported by proof-of-concept experiments revealing that targeting the
      ETC's Q-cycle by inhibition of both PfNDH2 and the bc(1) complex is highly
      synergistic. The potential of targeting PfNDH2 as a chemotherapeutic strategy for
      drug development is discussed.

PMID- 16641459
TI  - Nebulized amphotericin B combined with intravenous amphotericin B in rats with
      severe invasive pulmonary aspergillosis.
AB  - Nebulized amphotericin B (AMB) combined with intravenous AMB was studied in
      persistently leukopenic rats with invasive pulmonary aspergillosis. Pulmonary
      concentrations of AMB after aerosol treatment were substantially higher than
      after intravenous liposomal AMB. Nebulized liposomal AMB in addition to
      intravenous AMB resulted in significantly prolonged survival compared to
      controls.

PMID- 16641460
TI  - Streptococcus pneumoniae isolates resistant to telithromycin.
AB  - The telithromycin susceptibility of 210 erythromycin-resistant pneumococci was
      tested with the agar diffusion method. Twenty-six erm(B)-positive isolates showed
      heterogeneous resistance to telithromycin, which was manifested by the presence
      of colonies inside the inhibition zone. When these cells were cultured and
      tested, they showed stable, homogeneous, and high-level resistance to
      telithromycin.

PMID- 16641461
TI  - Curcumin-artemisinin combination therapy for malaria.
AB  - Artemisinin and curcumin show an additive interaction in killing Plasmodium
      falciparum in culture. In vivo, 3 oral doses of curcumin following a single
      injection of alpha,beta-arteether to Plasmodium berghei-infected mice are able to
      prevent recrudescence due to alpha,beta-arteether monotherapy and ensure almost
      100% survival of the animals.

PMID- 16641462
TI  - Extended-spectrum beta-lactamases and plasmid-mediated AmpC enzymes among
      clinical isolates of Escherichia coli and Klebsiella pneumoniae from seven
      medical centers in Taiwan.
AB  - Production of extended-spectrum beta-lactamases and plasmid-mediated AmpC enzymes
      was investigated among 291 Escherichia coli and 282 Klebsiella pneumoniae
      isolates that showed decreased susceptibilities to extended-spectrum
      cephalosporins from seven Taiwanese medical centers. CTX-M-type and SHV-type
      enzymes were the most prevalent extended-spectrum beta-lactamases. CMY-2-like and
      DHA-1-like beta-lactamases were the most prevalent AmpC-type enzymes.

PMID- 16641463
TI  - Comparative in vitro efficacies of various catheter lock solutions.
AB  - MEDTA (minocycline-edetate calcium disodium), taurolidine (2%)
      polyvinylpyrolidine (5%) (T/PVP), and ethanol as potential catheter lock
      solutions have a unique mechanism of action, broad-spectrum activity, and
      anticoagulant properties. Traditional lock solutions minocycline (M), rifampin
      (R), ciprofloxacin (C), and vancomycin, except pharmacologic concentrations of C
      and R and of M and R, were less effective than MEDTA and T/PVP.

PMID- 16641464
TI  - Pharmacokinetics of a new, orally available ceftriaxone formulation in physical
      complexation with a cationic analogue of bile acid in rats.
AB  - Oral administration of ceftriaxone associated with a bile acid-based new oral
      carrier, cholylethylenediamine, in 50% propylene glycol to rats at doses of 25
      and 50 mg/kg of body weight resulted in a significant increase in intestinal
      absorption, as evidenced by 55% improvement in the bioavailability, whereas
      ceftriaxone alone showed a bioavailability of less than 1%.

PMID- 16641465
TI  - Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated
      from an untreated human patient.
AB  - An influenza B virus from an infant with no history of treatment or contact with
      neuraminidase inhibitors demonstrated a significant reduction in sensitivity to
      these drugs. Here, we describe the analysis of a mixed viral population that
      contained a novel D197E amino acid substitution that was responsible for this
      reduction.

PMID- 16641466
TI  - Erythromycin and clindamycin resistance in group B streptococcal clinical
      isolates.
AB  - Erythromycin (EM) and clindamycin (CM) susceptibility testing was performed on
      222 clinical isolates of group B Streptococcus. A multiplex PCR assay was used to
      detect the ermB, ermTR, and mefA/E antibiotic resistance genes. These results
      were compared to the phenotypes as determined by the standard EM/CM double disk
      diffusion assay.

PMID- 16641467
TI  - Intrapulmonary penetration of voriconazole in patients receiving an oral
      prophylactic regimen.
AB  - Voriconazole penetrated well into the pulmonary epithelial lining fluid (ELF) in
      lung transplant patients receiving oral prophylaxis. The ELF concentrations
      exceeded those of the plasma, with an average ELF-to-plasma ratio of 11 (+/-8). A
      strong association between plasma and ELF concentrations (r(2) = 0.95) was noted.

PMID- 16641468
TI  - Effect of a nutritional supplement on posaconazole pharmacokinetics following
      oral administration to healthy volunteers.
AB  - We conducted a randomized, crossover study in healthy adults to examine the
      effects of a nutritional supplement (Boost Plus) on posaconazole
      pharmacokinetics. In this study, coadministration of posaconazole with Boost Plus
      increased the maximum concentration of posaconazole in serum and area under the
      concentration-time curve from 0 to 72 h values 3.4- and 2.6-fold, respectively,
      compared to those for the fasted state.

PMID- 16641469
TI  - Increasing prevalence and diversity of metallo-beta-lactamases in Pseudomonas
      spp., Acinetobacter spp., and Enterobacteriaceae from Korea.
AB  - Among imipenem-nonsusceptible isolates, acquired metallo-beta-lactamase genes
      were detected in 36 of 581 (6.2%) Pseudomonas aeruginosa isolates, 42 of 44
      (95.4%) other Pseudomonas species, and 136 of 513 (26.5%) Acinetobacter species
      from 2003 to 2004 at a Korean hospital. Overall, bla(VIM-2)-like genes were the
      most prevalent and were also detected in Enterobacteriaceae, including Klebsiella
      pneumoniae.

PMID- 16641470
TI  - In vitro activities of DX-619 and four comparator agents against 376 anaerobic
      bacterial isolates.
AB  - The activity of DX-619 was evaluated against 376 anaerobic isolates using the
      reference CLSI agar dilution method. Overall, 90% of the strains were susceptible
      to DX-619 at < or =1 microg/ml. It was more active than the other four compounds
      tested except for meropenem, which showed virtually identical overall activity.

PMID- 16641471
TI  - Antimicrobial susceptibility pattern of Clostridium difficile and its relation to
      PCR ribotypes in a Swedish university hospital.
AB  - All 238 Clostridium difficile isolates were susceptible to metronidazole and
      vancomycin, whereas 84% and 1% were resistant to clindamycin and fusidic acid.
      Etest MICs for metronidazole were lower than agar dilution MICs (P < 0.01) but
      without difference in susceptible-intermediate-resistant categorization. No
      particular PCR ribotype was associated with clindamycin or fusidic acid
      resistance.

PMID- 16641472
TI  - Selection of Plasmodium falciparum pfmdr1 alleles following therapy with
      artemether-lumefantrine in an area of Uganda where malaria is highly endemic.
AB  - Polymorphisms in the Plasmodium falciparum pfmdr1 gene were assayed in
      pretreatment samples and in samples from patients reinfected following therapy
      with artemether-lumefantrine. The pfmdr1 alleles 86N, 184F, and 1246D
      significantly increased in prevalence after treatment. All samples had a single
      pfmdr1 copy. Treatment with artemether-lumefantrine selects for polymorphisms
      that may alter antimalarial drug response.

PMID- 16641473
TI  - Macrolide-resistant Streptococcus pyogenes in Norway: population structure and
      resistance determinants.
AB  - A 2.7% prevalence of macrolide resistance in 1,657 Norwegian clinical
      Streptococcus pyogenes isolates was primarily due to erm(TR) (59%) and mef(A)
      (20%). Four clonal complexes comprised 75% of the strains. Macrolide resistance
      in S. pyogenes in Norway is imported as resistant strains or locally selected in
      internationally disseminated susceptible clones.

PMID- 16641474
TI  - Significance of mutations in embB codon 306 for prediction of ethambutol
      resistance in clinical Mycobacterium tuberculosis isolates.
AB  - We analyzed 159 Mycobacterium tuberculosis isolates (101 ethambutol [EMB]
      resistant strains, 33 multidrug-resistant but not EMB-resistant strains, and 25
      fully susceptible strains) for the presence of mutations in embB codon 306
      (embB306). Mutations were detected only in EMB-resistant strains (n = 69; 68%),
      thus confirming the significance of embB306 mutations for the prediction of
      resistance to EMB.

PMID- 16641475
TI  - Vibrio cholerae InV117, a class 1 integron harboring aac(6')-Ib and blaCTX-M-2,
      is linked to transposition genes.
AB  - A ca. 150-kbp Vibrio cholerae O1 biotype El Tor plasmid includes bla(CTX-M-2) and
      a variant of aac(6')-Ib within InV117, an orf513-bearing class 1 integron. InV117
      is linked to a tnp1696 module in which IRl carries an insertion of IS4321R. The
      complete structure could be a potential mobile element.

PMID- 16641476
TI  - Activity of novel benzoxazinorifamycins against rifamycin-resistant Streptococcus
      pyogenes.

PMID- 16641477
TI  - Is linezolid superior to vancomycin for complicated skin and soft tissue
      infections due to methicillin-resistant Staphylococcus aureus?

PMID- 16641478
TI  - New antimicrobial agents approved by the U.S. Food and Drug Administration in
      2005 and new indications for previously approved agents.

PMID- 16641479
TI  - Brief report: the risk of posttraumatic stress disorder in mothers of children
      diagnosed with pediatric cancer and type I diabetes.
AB  - OBJECTIVE: To evaluate the risk of and predictors of enduring and late-onset
      posttraumatic stress disorder (PTSD) among mothers of children diagnosed with
      type I diabetes and cancer. METHOD: Mothers (N = 99) of children diagnosed with
      cancer or diabetes for at least 12 months completed a structured clinical
      interview for PTSD and self-report measures of PTSD, depression, anxiety, and
      stressful life events. RESULTS: There was no significant difference in the rate
      of PTSD between the two groups. Overall, fewer mothers (7%) met criteria for PTSD
      on the structured clinical interview than those on a self-report measure of PTSD
      (17%). Mothers who reported more depressive symptoms, anxiety, and stressful life
      events tended to report significantly more PTSD symptoms. CONCLUSIONS: The
      findings extend prior research regarding the prevalence rate and predictors of
      PTSD and PTSD symptoms in pediatric populations. It is recommended that
      clinicians exercise caution when interpreting prevalence rates for PTSD that are
      derived from self-report measures.

PMID- 16641480
TI  - Prospective psychological evaluation of pediatric heart and heart-lung
      recipients.
AB  - OBJECTIVE: To study psychological adjustment in children and adolescents before
      undergoing heart or heart-lung transplantation and to reevaluate them at 6, 12,
      and 24 months after surgery. METHODS: Previously validated measures of behavior
      and depression were administered to children, their parents, and teachers.
      Parents also completed a measure of distress. RESULTS: Before transplantation,
      participants and parents obtained significantly higher scores on measures of
      behavior and psychological distress than children with no health problems and
      their parents, but 1 year after transplant, there were no significant differences
      between the two groups. Over time, there were significant improvements in
      depression and behavior scores in the group who had undergone transplantation.
      CONCLUSION: Despite improvements in psychological functioning over time, a
      significant minority of children and adolescents undergoing transplantation are
      at risk for psychological adjustment difficulties. Psychological interventions to
      reduce morbidity need to be implemented and evaluated.

PMID- 16641481
TI  - Testing positive for methadone and either a tricyclic antidepressant or a
      benzodiazepine is associated with an accidental overdose death: analysis of
      medical examiner data.
AB  - OBJECTIVES: Patients in emergency departments who use methadone frequently use
      tricyclic antidepressants (TCAs) and/or benzodiazepines (BZDs). This is a
      potentially dangerous drug combination. The authors hypothesized that the
      presence of methadone and a TCA, a BZD, or both is associated with an
      "accidental" overdose (AOD) death more often than a death from any other cause.
      METHODS: A retrospective chart review of New York City Office of Chief Medical
      Examiner data for 2003 was performed. Decedents who tested positive for methadone
      that were classified as an AOD death, as determined by the medical examiner, were
      compared with deaths from all other causes for the presence of a TCA, a BZD, or
      both. A logistical regression was performed to develop a multivariate model
      identifying additional variables associated with a methadone-positive AOD death.
      A p-value of <0.05 was considered significant, and 95% confidence intervals (CIs)
      were calculated. RESULTS: In 2003, there were 5,817 medical examiner cases, of
      which 500 (8.6%) were methadone positive. Of the methadone-positive cases, 493
      were available for analysis; 95 (19.3%) were TCA positive and 158 (32.0%) were
      BZD positive. The odds of having an AOD death in methadone-positive decedents
      testing TCA positive, BZD positive, or both were 2.11 (95% CI = 1.32 to 3.37; p <
      0.01) for TCAs, 1.66 (95% CI = 1.12 to 2.45; p < 0.02) for BZDs, and 4.34 (95% CI
      = 1.97 to 9.56; p < 0.001) for both. The multivariate logistic regression of
      analytes revealed the following covariates associated with an AOD death as well:
      amitriptyline, cocaine, morphine, or opiates. CONCLUSIONS: Among the methadone
      positive cases, testing positive for a TCA, a BZD, or both was associated with an
      AOD death.

PMID- 16641482
TI  - Droperidol use in the emergency department is not safe.

PMID- 16641483
TI  - Management of acute undifferentiated agitation in the emergency department.

PMID- 16641485
TI  - 3-Nitrotyrosine as a spectroscopic probe for investigating protein protein
      interactions.
AB  - 3-Nitrotyrosine (NT) is approximately 10(3)-fold more acidic than Tyr, and its
      absorption properties are strongly pH-dependent. NT absorbs radiation in the
      wavelength range where Tyr and Trp emit fluorescence (300-450 nm), and it is
      essentially nonfluorescent. Therefore, NT may function as an energy acceptor in
      resonance energy transfer (FRET) studies for investigating ligand protein
      interactions. Here, the potentialities of NT were tested on the hirudin thrombin
      system, a well-characterized protease inhibitor pair of key pharmacological
      importance. We synthesized two analogs of the N-terminal domain (residues 1-47)
      of hirudin: Y3NT, in which Tyr3 was replaced by NT, and S2R/Y3NT, containing the
      substitutions Ser2 --> Arg and Tyr3 --> NT. The binding of these analogs to
      thrombin was investigated at pH 8 by FRET and UV/Vis-absorption spectroscopy.
      Upon hirudin binding, the fluorescence of thrombin was reduced by approximately
      50%, due to the energy transfer occurring between the Trp residues of the enzyme
      (i.e., the donors) and the single NT of the inhibitor (i.e., the acceptor). The
      changes in the absorption spectra of the enzyme inhibitor complex indicate that
      the phenate moiety of NT in the free state becomes protonated to phenol in the
      thrombin-bound form. Our results indicate that the incorporation of NT can be
      effectively used to detect protein protein interactions with sensitivity in the
      low nanomolar range, to uncover subtle structural features at the ligand protein
      interface, and to obtain reliable Kd values for structure activity relationship
      studies. Furthermore, advances in chemical and genetic methods, useful for
      incorporating noncoded amino acids into proteins, highlight the broad
      applicability of NT in biotechnology and pharmacological screening.

PMID- 16641486
TI  - Comparison of crystal structures of human androgen receptor ligand-binding domain
      complexed with various agonists reveals molecular determinants responsible for
      binding affinity.
AB  - Androgens exert their effects by binding to the highly specific androgen receptor
      (AR). In addition to natural potent androgens, AR binds a variety of synthetic
      agonist or antagonist molecules with different affinities. To identify molecular
      determinants responsible for this selectivity, we have determined the crystal
      structure of the human androgen receptor ligand-binding domain (hARLBD) in
      complex with two natural androgens, testosterone (Testo) and dihydrotestosterone
      (DHT), and with an androgenic steroid used in sport doping, tetrahydrogestrinone
      (THG), at 1.64, 1.90, and 1.75 A resolution, respectively. Comparison of these
      structures first highlights the flexibility of several residues buried in the
      ligand-binding pocket that can accommodate a variety of ligand structures. As
      expected, the ligand structure itself (dimension, presence, and position of
      unsaturated bonds that influence the geometry of the steroidal nucleus or the
      electronic properties of the neighboring atoms, etc.) determines the number of
      interactions it can make with the hARLBD. Indeed, THG--which possesses the
      highest affinity--establishes more van der Waals contacts with the receptor than
      the other steroids, whereas the geometry of the atoms forming electrostatic
      interactions at both extremities of the steroid nucleus seems mainly responsible
      for the higher affinity measured experimentally for DHT over Testo. Moreover,
      estimation of the ligand-receptor interaction energy through modeling confirms
      that even minor modifications in ligand structure have a great impact on the
      strength of these interactions. Our crystallographic data combined with those
      obtained by modeling will be helpful in the design of novel molecules with
      stronger affinity for the AR.

PMID- 16641487
TI  - An algorithm for predicting protein-protein interaction sites: Abnormally exposed
      amino acid residues and secondary structure elements.
AB  - Multiprotein systems mediate most regulatory processes in living organisms.
      Although the structures of the individual proteins are often defined, less is
      known of the structures of multiprotein systems. Computational methods for
      predicting interfaces, using evolutionary conservation and/or physicochemical
      data, have been developed. Here we consider the use of solvent accessibility,
      residue propensity, and hydrophobicity, in conjunction with secondary structure
      data, as prediction parameters. We analyze the influence of residue type and
      secondary structure on solvent accessibility and define a measure of "relative
      exposedness." Clustering abnormally high scoring residues provides a basis for
      predicting interaction sites. The analysis is extended to investigate abnormally
      exposed secondary structure elements, particularly beta-sheet strands. We show
      that surface-exposed beta-strands lacking protective features are more likely to
      be found at protein-protein interfaces, allowing us to create an algorithm with
      approximately 68% and approximately 75% accuracy in differentiating between
      interacting and edge strands in isolated beta-strands and beta-sheet strands,
      respectively. These methods of identifying abnormally exposed surface regions are
      combined in an algorithm, which, on a data set of 77 unbound and disjoint (single
      chain extracted from complex) structures, predicts 79% of the protein-protein
      interfaces correctly. If enzyme-inhibitor complexes, where the inhibitor mimics a
      nonprotein substrate, are excluded, the accuracy increases to 85%.

PMID- 16641488
TI  - Tunnel plasticity and quaternary structural integrity of a pentameric protein
      ring.
AB  - Cyclic protein oligomers are common in cells. However, the importance of the
      residues that line the central tunnel of protein rings for overall architectural
      integrity is not well understood. To investigate the role of tunnel positions in
      protein assembly and stability, we prepared variants of the homo-pentameric
      lumazine synthase (LS) from Saccharomyces cerevisiae in which the three residues
      that line the middle of the tunnel were simultaneously changed. As a consequence
      of symmetry, these mutations cause a total of 15 changes in the structure of the
      pentameric complex. Detailed characterization of the variants indicates that they
      retain quaternary structural integrity, even in cases where the mutations induce
      considerable secondary structure alterations. The tunnels of symmetric ring
      shaped proteins, such as LS, may consequently represent an overlooked site for
      protein engineering.

PMID- 16641489
TI  - Stoichiometry of lipid interactions with transmembrane proteins--Deduced from the
      3D structures.
AB  - The stoichiometry of the first shell of lipids interacting with a transmembrane
      protein is defined operationally by the population of spin-labeled lipid chains
      whose motion is restricted directly by the protein. Interaction stoichiometries
      have been determined experimentally for a wide range of alpha-helical integral
      membrane proteins by using spin-label ESR spectroscopy. Here, we determine the
      spatially defined number of first-shell lipids at the hydrophobic perimeter of
      integral membrane proteins whose 3D structure has been determined by X-ray
      crystallography and lipid-protein interactions characterized by spin-labeling.
      Molecular modeling is used to build a single shell of lipids surrounding
      transmembrane structures derived from the PDB. Constrained energy optimization of
      the protein-lipid assemblies is performed by molecular mechanics. For relatively
      small proteins (up to 7-12 transmembrane helices), the geometrical first shell
      corresponds to that defined experimentally by perturbation of the lipid-chain
      dynamics. For larger, multi-subunit alpha-helical proteins, the lipids perturbed
      directly by the protein may either exceed or be less in number than those that
      can be accommodated at the intramembranous perimeter. In these latter cases, the
      motionally restricted spin-labeled lipids can be augmented by intercalation, or
      can correspond to a specific subpopulation at the protein interface,
      respectively. For monomeric beta-barrel proteins, the geometrical lipid
      stoichiometry corresponds to that determined from lipid mobility for a 22
      stranded barrel, but fewer lipids are motionally restricted than can be
      accommodated around an eight-stranded barrel. Deviations from the geometrical
      first shell, in the beta-barrel case, are for the smaller protein with a highly
      curved barrel.

PMID- 16641490
TI  - Probing the collective vibrational dynamics of a protein in liquid water by
      terahertz absorption spectroscopy.
AB  - Biological polymers are expected to exhibit functionally relevant, global, and
      subglobal collective modes in the terahertz (THz) frequency range (i.e.,
      picosecond timescale). In an effort to monitor these collective motions, we have
      experimentally determined the absorption spectrum of solvated bovine serum
      albumin (BSA) from 0.3 to 3.72 THz (10-124 cm(-1)). We successfully extract the
      terahertz molar absorption of the solvated BSA from the much stronger attenuation
      of water and observe in the solvated protein a dense, overlapping spectrum of
      vibrational modes that increases monotonically with increasing frequency. We see
      no evidence of distinct, strong, spectral features, suggesting that no specific
      collective vibrations dominate the protein's spectrum of motions, consistent with
      the predictions of molecular dynamics simulations and normal mode analyses of a
      range of small proteins. The shape of the observed spectrum resembles the ideal
      quadratic spectral density expected for a disordered ionic solid, indicating that
      the terahertz normal mode density of the solvated BSA may be modeled, to first
      order, as that of a three-dimensional elastic nanoparticle with an aperiodic
      charge distribution. Nevertheless, there are important detailed departures from
      that of a disordered inorganic solid or the normal mode densities predicted for
      several smaller proteins. These departures are presumably the spectral features
      arising from the unique molecular details of the solvated BSA. The techniques
      used here and measurements have the potential to experimentally confront
      theoretical calculations on a frequency scale that is important for
      macromolecular motions in a biologically relevant water environment.

PMID- 16641491
TI  - Structure of the Sir3 protein bromo adjacent homology (BAH) domain from S.
      cerevisiae at 1.95 A resolution.
AB  - Sir3p is a silent-information-regulator (SIR) protein required for the assembly
      of a transcriptionally "silent" chromatin structure at telomeres and the cryptic
      HM mating-type loci in Saccharomyces cerevisiae. Sir3p contains a putative "bromo
      adjacent homology" (BAH) domain at its N terminus that shares strong sequence
      similarity with the BAH domain of a subunit of the origin recognition complex
      (ORC), Orc1p. The Orc1p-BAH domain forms a well-defined complex with the ORC
      interaction region (OIR) of another Sir protein, Sir1p, which targets formation
      of silent chromatin to the HM-loci. Interestingly, despite sequence similarity of
      the Sir3p and Orc1p BAH domains and Sir3p's established importance in silencing,
      Sir3p does not bind the Sir1p-OIR. Here we report the 1.95 A resolution crystal
      structure of the Sir3p-BAH domain. The structure reveals two key features that
      can account for Sir3p-BAH domain's inability to interact with Sir1p. First,
      several Orc1p-BAH domain residues known to directly contact Sir1p are altered in
      the Sir3p-BAH domain. Second, a critical OIR-binding pocket present on the
      surface of the Orc1p-BAH domain is "filled" in the Sir3p-BAH domain structure,
      potentially making it inaccessible to Sir1p. These findings imply that the Sir3p
      BAH domain structure has evolved for functions distinct from those of the Orc1p
      BAH domain.

PMID- 16641492
TI  - Ligand binding by TPR domains.
AB  - Tetratricopeptide repeat (TPR) domains bind specific peptide ligands and are
      thought to mediate protein-protein interactions in a variety of biological
      systems. Here we compare peptide ligand-binding by several different TPR domains.
      We present specific examples that demonstrate that TPR domains typically undergo
      little or no structural rearrangement upon ligand binding. Our data suggest that,
      contrary to a recent proposal, coupled folding and binding is not the common
      mechanism of ligand recognition by TPR domains.

PMID- 16641493
TI  - Crystal structure of human peptidoglycan recognition protein I alpha bound to a
      muramyl pentapeptide from Gram-positive bacteria.
AB  - Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of
      the innate immune system that bind bacterial peptidoglycans (PGNs). We determined
      the crystal structure, to 2.1 A resolution, of the C-terminal PGN-binding domain
      of human PGRP-I alpha in complex with a muramyl pentapeptide (MPP) from Gram
      positive bacteria containing a complete peptide stem (L-Ala-D-isoGln-L-Lys-D-Ala
      D-Ala). The structure reveals important features not observed previously in the
      complex between PGRP-I alpha and a muramyl tripeptide lacking D-Ala at stem
      positions 4 and 5. Most notable are ligand-induced structural rearrangements in
      the PGN-binding site that are essential for entry of the C-terminal portion of
      the peptide stem and for locking MPP in the binding groove. We propose that
      similar structural rearrangements to accommodate the PGN stem likely characterize
      many PGRPs, both mammalian and insect.

PMID- 16641494
TI  - 2005 Emil Thomas Kaiser Award.
AB  - Collagen is the most abundant protein in animals. The conformational stability of
      the collagen triple helix is enhanced by the hydroxyl group of its prevalent
      (2S,4R)-4-hydroxyproline residues. For 25 years, the prevailing paradigm had been
      that this enhanced stability is due to hydrogen bonds mediated by bridging water
      molecules. We tested this hypothesis with synthetic collagen triple helices
      containing 4-fluoroproline residues. The results have unveiled a wealth of
      stereoelectronic effects that contribute markedly to the stability of collagen,
      as well as other proteins. This new understanding is leading to synthetic
      collagens for a variety of applications in biotechnology and biomedicine.

PMID- 16641496
TI  - The north-south incapacity divide.

PMID- 16641497
TI  - The role of the occupational physician in the enlarged European Union: challenges
      and opportunities.

PMID- 16641498
TI  - Why I became an occupational physician ...

PMID- 16641499
TI  - Ionizing radiation: overview.

PMID- 16641500
TI  - New advances in radiation biology.
AB  - Current understanding of risk associated with low-dose radiation exposure has for
      many years been embedded in the linear-no-threshold (LNT) approach, based on
      simple extrapolation from the Japanese atomic bomb survivors. Radiation biology
      research has supported the LNT approach although much of this has been limited to
      relatively high-dose studies. Recently, with new advances for studying effects of
      low-dose exposure in experimental models and advances in molecular and cellular
      biology, a range of new effects of biological responses to radiation has been
      observed. These include genomic instability, adaptive responses and bystander
      effects. Most have one feature in common in that they are observed at low doses
      and suggest significant non-linear responses. These new observations pose a
      significant challenge to our understanding of low-dose exposure and require
      further study to elucidate mechanisms and determine their relevance.

PMID- 16641501
TI  - Medical management of radiation injuries: current approaches.
AB  - The current approach to medical management of irradiated patients begins with
      early diagnosis of radiation injury. Medical assessment of radiation dose is
      based on event history, symptomatology and laboratory results, with emphasis on
      time to emesis and lymphocyte depletion kinetics. Dose assessment provides a
      basis for early use of haematopoietic growth factors that can shorten the period
      of neutropaenia for patients with acute radiation syndrome. Assessments of
      haematopoietic, gastrointestinal and cutaneous syndromes have improved in recent
      years, but treatment options remain limited. Selected examples of current
      developments are presented.

PMID- 16641502
TI  - Occupational exposure, epidemiology and compensation.

PMID- 16641503
TI  - Intervention in the event of a radiation emergency: the basis for UK planning.

PMID- 16641504
TI  - Leisure time physical activity and sickness absenteeism; a prospective study.
AB  - AIM: To establish whether workers with frequent leisure time physical activities
      are at higher or lower risk of sickness absence compared to inactive workers.
      METHOD: Self reported and company recorded sickness absence data were collected
      during 18 months of follow-up for 8902 workers. Frequency of leisure time
      physical activities was queried at baseline. RESULTS: Overall, we found that
      workers active in their leisure time twice or more each week reported
      significantly less sickness absence compared to inactive workers (14.8 versus
      19.5 days/year), mainly due to a decrease in sick leave because of
      musculoskeletal disorders. CONCLUSION: Demotivating sports participation by
      making workers liable for workdays lost due to sporting injuries might be counter
      productive in decreasing absenteeism and its related costs. Promoting worker
      participation in sport might lead to reduced absenteeism.

PMID- 16641505
TI  - Re: Evaluation of an occupational health service for general practitioners and
      their staff in a primary care trust.

PMID- 16641506
TI  - Re: Mortality experience of male workers at a UK tin smelter.

PMID- 16641507
TI  - Ill-health retirement.

PMID- 16641508
TI  - Work disability from rheumatoid arthritis.

PMID- 16641509
TI  - The Hawthorne effect.

PMID- 16641511
TI  - Processing body autoantibodies reconsidered.
AB  - Processing bodies (P-bodies) are cellular structures that have critical roles in
      mRNA degradation and post-transcriptional gene silencing. Some patients with
      autoimmune disease have high titer antibodies directed against P-bodies, and
      certain sera have been used as markers for the GW182 component of these
      structures. This study shows that available reference sera are unreliable markers
      for GW182 because the sera contain antibodies directed against Ge-1, a second P
      body autoantigen.

PMID- 16641512
TI  - Isolation and identification of an epibiotic bacterium associated with
      heterocystous Anabaena cells.

PMID- 16641513
TI  - Mechanisms of gravitaxis in Chlamydomonas.

PMID- 16641514
TI  - Field behavior of the nudibranch mollusc Tritonia diomedea.
AB  - The nudibranch mollusc Tritonia diomedea has been a useful model system for
      studies of how the brain controls behavior. However, no broad study of T.
      diomedea field behavior exists--an important deficit since laboratory behaviors
      may differ from what occurs in nature. Here we report analysis of time-lapse
      video of the slugs in their natural habitat to describe behaviors and their
      relationships to sensory cues. We found that movements relative to conspecifics,
      prey, and predators correlated with direction of water flow. These observations
      lead to three new navigational hypotheses: regardless of the actual heading to
      the target, T. diomedea crawls (1) upstream toward potential mates, (2) upstream
      toward food, and (3) downstream away from predators. We also describe both the
      behavior and its sensory context for feeding, escape swims, mating, and egg
      laying, among other behaviors. Field behaviors were similar to published
      descriptions of laboratory behavior. However, the field observations add
      contextual detail, including preceding and subsequent behaviors and interactions
      with suites of habitat features not present in the laboratory. For example, the
      escape swim, previously studied as an isolated behavior in response to a single
      stimulus, appears to be affected by multiple sensory modalities and coordinated
      with several other behaviors. Our work will provide a basis for future
      neuroethological experimentation and also is the first step in the study of
      navigation in T. diomedea.

PMID- 16641515
TI  - Orientation and navigation relative to water flow, prey, conspecifics, and
      predators by the nudibranch mollusc Tritonia diomedea.
AB  - Progress in understanding sensory and locomotory systems in Tritonia diomedea has
      created the potential for the neuroethological study of animal navigation in this
      species. Our goal is to describe the navigational behaviors to guide further work
      on how the nervous system integrates information from multiple senses to produce
      oriented locomotion. Observation of T. diomedea in its habitat has suggested that
      it uses water flow to navigate relative to prey, predators, and conspecifics. We
      test these hypotheses in the field by comparing slug orientation in time-lapse
      videos to flow direction in circumstances with and without prey, predators, or
      conspecifics upstream. T. diomedea oriented upstream both while crawling and
      after turning. This trend was strongest before feeding or mating; after feeding
      or mating, the slugs did not orient significantly to flow. Slugs turned
      downstream away from an upstream predator but did not react in control situations
      without an upstream predator. These data support the hypothesis that T. diomedea
      uses a combination of odors (or some other cue transported downstream) and water
      flow to navigate relative to prey, predators, and conspecifics. Understanding the
      context-dependent choice between upstream and downstream crawling in T. diomedea
      provides an opportunity for further work on the sensory integration underlying
      navigation behavior.

PMID- 16641516
TI  - Programmed cell death in the apical ganglion during larval metamorphosis of the
      marine mollusc Ilyanassa obsoleta.
AB  - The apical ganglion (AG) of larval caenogastropods, such as Ilyanassa obsoleta,
      houses a sensory organ, contains five serotonergic neurons, innervates the
      muscular and ciliary components of the velum, and sends neurites into a neuropil
      that lies atop the cerebral commissure. During metamorphosis, the AG is lost.
      This loss had been postulated to occur through some form of programmed cell death
      (PCD), but it is possible for cells within the AG to be respecified or to migrate
      into adjacent ganglia. Evidence from histological sections is supported by
      results from a terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assay, which indicate that cells of the AG degenerate by PCD. PCD occurs
      after metamorphic induction by serotonin or by inhibition of nitric oxide
      synthase (NOS) activity. Cellular degeneration and nuclear condensation and loss
      were observed within 12 h of metamorphic induction by NOS inhibition and occur
      before loss of the velar lobes, the ciliated tissue used for larval swimming and
      feeding. Velar disintegration happens more rapidly after metamorphic induction by
      serotonin than by 7-nitroindazole, a NOS inhibitor. Loss of the AG was complete
      by 72 h after induction. Spontaneous loss of the AG in older competent larvae may
      arise from a natural decrease in endogenous NOS activity, giving rise to the
      tendency of aging larvae to display spontaneous metamorphosis in culture.

PMID- 16641517
TI  - Role of protein kinase C, G-protein coupled receptors, and calcium flux during
      metamorphosis of the sea urchin Strongylocentrotus purpuratus.
AB  - Artificial inducers have been used to study signal-transduction pathways involved
      in metamorphosis of some marine invertebrates. However, the transduction
      mechanisms for echinoderms have been less explored. In the present study,
      participation of protein kinase C (PKC), G-protein-coupled receptors (GPCRs), and
      calcium has been investigated during metamorphosis of the sea urchin
      Stronglylocentrotus purpuratus. Competent larvae were induced with different
      drugs that activate (PKC and GP activators, Ca2+ ionophores, and inhibitors of
      Ca2+ ATPase) or inhibit (PKC, G-protein, and Ca2+ flux inhibitors) metamorphosis.
      Six of the compounds were effective: the PKC activators TPA and indolactam; the G
      protein inhibitors suramin and guanosine; the calcium ionophore A23187, and the
      calcium ATPase inhibitor thapsigargin. TPA was effective at 0.001 microM;
      indolactam was effective at 0.001 microM. In the presence of KCl as inducer, the
      G-protein inhibitor suramin was effective at 10 microM and guanosine at 0.001
      microM. In the presence of a bacterial film as inducer, suramin was effective at
      50 microM, and guanosine inhibited metamorphosis at 1 microM. A23187 was
      effective at 5 and 10 microM and thapsigargin at 50 and 100 microM. Our results
      indicate that GPCRs, protein kinase C, and calcium participate in the
      metamorphosis of S. purpuratus. These elements of the transduction pathways
      triggered during metamorphosis may be part of a cascade of signal transduction
      routes that interact from induction to the end of the morphogenetic events that
      shape the postlarval form. In addition, according to the results obtained with G
      protein inhibitors, the GPCRs may be shared between the artificial (KCl) and
      natural (biofilm) inducers.

PMID- 16641518
TI  - Effect of salinity on osmoregulatory patch epithelia in gills of the blue crab
      Callinectes sapidus.
AB  - In euryhaline crabs, ion-transporting cells are clustered into osmoregulatory
      patches on the lamellae of the posterior gills. To examine changes in the
      branchial osmoregulatory patch in the blue crab Callinectes sapidus in response
      to change in salinity and to correlate these changes with other osmoregulatory
      responses, crabs were acclimated to a range of salinities between 10 and 35 ppt.
      When crabs that had been acclimated to 35 ppt were subsequently transferred to 10
      ppt, both the size of the osmoregulatory patch on individual gill lamellae and
      the specific activity of Na+, K+-ATPase in whole-gill homogenates increased only
      after the first 24 h of exposure to dilute seawater. Enzyme activity and size of
      patch area increased gradually and reached their maxima (increasing by 200% and
      60%, respectively) 6 days following transfer to 10 ppt seawater and then remained
      at these levels. Patch size at acclimation varied inversely with the salinity for
      seawater dilutions below 26 ppt (the isosmotic point of the crab), although it
      did not vary in salinities at or above 26 ppt. Thus, the size of the patch
      clearly is modulated with acclimation salinity, but it increases only in those
      salinities in which the crab hyperosmoregulates. An increase in the total RNA/DNA
      ratio in gill homogenates, the lack of mitotic figures in the lamellae, and the
      lack of incorporation of bromodeoxyuridine into nuclei of lamellar epithelial
      cells during acclimation to dilute seawater were interpreted as evidence that no
      cell proliferation had occurred and that increases in the size of the
      osmoregulatory patch occurred through differentiation of existing gas exchange
      cells or of undifferentiated epithelial cells into ion-transporting cells.

PMID- 16641519
TI  - Migration, isolation, and speciation of hydrothermal vent limpets (Gastropoda;
      Lepetodrilidae) across the Blanco Transform Fault.
AB  - The Sovanco Fracture Zone and Blanco Transform Fault separate the Explorer, Juan
      de Fuca, and Gorda ridge systems of the northeastern Pacific Ocean. To test
      whether such offsets in the ridge axis create barriers to along-axis dispersal of
      the endemic hydrothermal vent animals, we examined the genetic structure of
      limpet populations previously identified as Lepetodrilus fucensis McLean, 1988
      (Gastropoda, Lepetodrilidae). Mitochondrial DNA sequences and patterns of
      allozyme variation revealed no evidence that the 150-km-long Sovanco Fracture
      Zone impeded gene flow between the Explorer and Juan de Fuca populations. In
      contrast, the 450-km-long Blanco Transform Fault separates the limpets into
      highly divergent northern and southern lineages that we recognize as distinct
      species. We describe southern populations from the Gorda Ridge (Seacliff) and
      Escanaba Trough as Lepetodrilus gordensis new species and refer northern
      populations from the Explorer and Juan de Fuca ridge systems to L. fucensis sensu
      stricto. The species are similar morphologically, but L. gordensis lacks a
      sensory neck papilla and has a more tightly coiled teleconch. To assess the
      degree of isolation between these closely related species, we used the Isolation
      with Migration method to estimate the time of population splitting, effective
      sizes of the ancestral and derived populations, and rates of migration across the
      Blanco Transform Fault.

PMID- 16641520
TI  - Morphological and genetic variation indicate cryptic species within Lamarck's
      little sea star, Parvulastra (=Patiriella) exigua.
AB  - The asterinid sea star Parvulastra exigua (Lamarck) is a common member of
      temperate intertidal marine communities from geographically widespread sites
      around the southern hemisphere. Individuals from Australian populations lay
      benthic egg masses (through orally directed gonopores) from which nonplanktonic
      offspring hatch and metamorphose without a dispersing planktonic larval phase.
      Scattered reports in the taxonomic literature refer to a similar form in southern
      Africa with aborally directed gonopores (and possibly broadcast spawning of
      planktonic eggs and larvae); such differences would be consistent with cryptic
      species variation. Surveys of morphology and mtDNA sequences have revealed
      cryptic species diversity in other asterinid genera. Here we summarize the
      taxonomic history of Lamarck's "Asterie exigue" and survey morphological
      variation (the location of the gonopores) for evidence that some P. exigua
      populations include cryptic species with a different mode of reproduction. We
      found strong evidence for multiple species in the form of two phenotypes and
      modes of reproduction (oral and aboral gonopore locations) in populations from
      southern Africa and islands in the Atlantic and Indian oceans. Both modes of
      reproduction have broad geographic ranges. These results are consistent with
      previously published genetic data that indicate multiple species in African and
      island (but not Australian) populations.

PMID- 16641521
TI  - Developments in basic science research.
AB  - The 13th Conference on Retroviruses and Opportunistic Infections featured a
      strong basic science program that provided new findings on the nature of HIV
      disease as well as surprises regarding the antiviral action of innate restriction
      factors.

PMID- 16641522
TI  - HIV pathogenesis and vaccine development.
AB  - Cautious optimism was a recurring theme of many of the AIDS vaccine-related
      presentations at the 13th annual Conference on Retroviruses and Opportunistic
      Infections. Several investigators suggested that the ability of HIV to escape
      cytotoxic T-lymphocyte responses may be more limited than previously thought, and
      encouraging results were presented regarding the ability of consensus ancestral
      sequences or polyvalent vaccines to increase the breadth of induced immune
      responses. A number of studies highlighted the potential efficacy of neutralizing
      antibodies: data from 2 groups suggested that neutralizing antibodies may play a
      role in preventing superinfection and previously unrecognized neutralizing
      epitopes were identified in the membrane proximal external region of envelope.
      Two studies documented that immunization with polyvalent simian immunodeficiency
      virus vaccines can induce sustained control of viremia following repeated low
      dose mucosal challenge with pathogenic SIVmac strains and provided hope for the
      potential of T-cell-based vaccines to slow disease progression.

PMID- 16641523
TI  - Epidemiology and prevention.
AB  - The 2006 Conference on Retroviruses and Opportunistic Infections marked the 13th
      year of this conference and the 25th anniversary of the first published cases of
      AIDS in gay men in Los Angeles. As noted in the opening plenary session, HIV has
      likely been present in the human population since the 1930s, and therefore
      represents a relatively recent disease for humans. However, by the end of 2005,
      more than 40 million persons were estimated to be living with HIV infection, and
      5 million new infections are occurring annually. Investigators at this year's
      conference presented a number of abstracts focused on the leading edge of the
      epidemic, HIV testing strategies, the role of acute versus chronic HIV infection
      in driving the epidemic, and the substantial progress being made in developing
      and testing a variety of biomedical prevention strategies.

PMID- 16641524
TI  - Neurologic complications of HIV disease and their treatments.
AB  - The 2006 Conference on Retroviruses and Opportunistic Infections was marked by a
      record number of presentations focused on the neurologic complications of HIV
      infection. Key findings included the identification of the high prevalence of HIV
      associated neurocognitive impairment (HNCI) in Western and East Asian
      populations; biomarkers that may be clinically useful in determining risk and
      treatment of HNCI, such as neurofilament protein, insulin resistance, leptin,
      soluble Fas, and total protein levels in cerebrospinal fluid; host genotypes that
      were associated with HNCI as well as antiretroviral toxic neuropathy; HIV
      envelope signature positions that were associated with HNCI and reduced CD4
      dependence; the importance of combined antiretroviral drug penetration into the
      central nervous system for control of HIV replication; and an effective treatment
      for painful sensory neuropathy (capsaicin) and provocative preclinical data on
      treatments for HIV-associated neurocognitive impairment (rosiglitazone,
      glatiramer immunization). Together, these findings heighten concern for
      persistent neurologic diseases in antiretroviral therapy-treated individuals but
      provide guidance for their improved identification and treatment.

PMID- 16641525
TI  - Complications of HIV disease and antiretroviral therapy.
AB  - As antiretroviral treatment regimens become more potent and easier to administer,
      differences in the rates of adverse events and complications associated with
      treatment will increasingly drive decisions regarding the selection of therapy.
      This year's Conference on Retroviruses and Opportunistic Infections featured a
      wide range of research directed toward understanding the pathogenesis, treatment,
      and long-term consequences of complications associated with HIV infection and the
      use of antiretroviral therapy in both resource-limited settings and in the
      developed world. This review will summarize information on complications of
      antiretroviral therapy in resource-limited settings, hepatitis C virus,
      tuberculosis, and discussion of metabolic, cardiovascular, and renal
      complications.

PMID- 16641526
TI  - Advances in antiretroviral therapy.
AB  - 2006 is the 25th anniversary of the AIDS epidemic and the 10th anniversary of the
      potent antiretroviral therapy era. During this period, the annual Conference on
      Retroviruses and Opportunistic Infections (CROI) has grown to represent one of
      the most important meetings of the year with respect to providing a forum for
      investigators to present the latest information on developments in the
      antiretroviral therapeutic arena. This year's conference maintained this
      tradition and was most notable for the presentations on new antiretroviral
      agents, therapeutic strategies including major results of treatment interruption
      studies, viral resistance, and encouraging results of antiretroviral rollout
      programs in the developing world which have brought us to the threshold of a new
      era in treatment and clinical investigation.

PMID- 16641527
TI  - Autophagy by podocytes in renal biopsy specimens.

PMID- 16641528
TI  - p53 biological network: at the crossroads of the cellular-stress response pathway
      and molecular carcinogenesis.
AB  - p53 as a key molecular node in the stress response pathway, including
      inflammation. p53 is involved in several critical pathways including cell cycle
      arrest, apoptosis, DNA repair, and cellular senescence, which are essential for
      normal cellular homeostasis and maintaining genome integrity. The alteration of
      the TP53 gene or posttranslational modification in the p53 protein can alter its
      response to cellular stress. The molecular archaeology of the TP53 mutation
      spectrum generates hypotheses concerning the etiology and molecular pathogenesis
      of human cancer. The spectrum of somatic mutations in the TP53 gene implicates
      environmental carcinogens, and both endogenous agents and processes in the
      etiology of human cancer.

PMID- 16641529
TI  - Vitamin B12 could be a "master key" in the regulation of multiple pathological
      processes.
AB  - Multifunctional systems must maintain homeostasis. Man is an ideal example of a
      system that constantly aspires to attain optimal regulation, even under the
      stress of severe disease. We assume that there are universal, interchangeable (as
      required) biologically active substances that regulate the system and try to keep
      it in balance. We propose that one of these substances is vitamin B12. Why
      vitamin B12? The list of organs and body systems in which vitamin B12 plays a
      functional role is constantly being added to. Vitamin B12 affects the normal
      growth of children, the peripheral and central nervous systems, bone marrow,
      skin, mucous membranes, bones, and vessels. It is possible that even when the
      serum cobalamin level is normal, treatment with vitamin B12 could correct defects
      caused by other biologically active substances. We call this phenomenon the
      "Master Key" effect. We suggest that this "Master Key" concept can be tested by
      treating diseases, such as recurrent stomatitis, various forms of
      hyperpigmentation, trophic ulcers, and burns, with vitamin B12, even if the B12
      serum level is normal.

PMID- 16641530
TI  - An epidural initial dose is unnecessary in combined spinal epidural anesthesia
      for Caesarean section.
AB  - Combined spinal epidural anesthesia is widely used for Caesarean section. Bolus
      administration of an epidural initial dose introduces the risk of drug flux from
      the epidural space to the subarachnoid space, and the volume effect of the
      initial dose may cause epidural top-up and extension of subarachnoid blockade.
      These problems may be avoided if the initial dose is not administered. This study
      investigated whether epidural continuous infusion without an initial dose
      (continuous group) can decrease postoperative pain as well as an epidural
      continuous infusion with an initial dose (initial dose group). Sixty-one patients
      undergoing elective Caesarean section were randomly assigned to the initial dose
      group or the continuous group. Twenty patients undergoing emergency Caesarean
      section with spinal anesthesia (spinal group) were also investigated to confirm
      that epidural block is effective for postoperative pain. Data in this study were
      obtained retrospectively from each patient's records. Between the initial dose
      group and the continuous group, there was no significant difference in the number
      of times flurbiprofen or pentazocine were used for postoperative pain relief.
      However, the number of times that pentazocine was used was significantly higher
      in the spinal group than in other groups. This finding suggests that an epidural
      initial dose is unnecessary for postoperative pain relief in combined spinal
      epidural anesthesia for Caesarean section.

PMID- 16641531
TI  - Light-emitting diode phototherapy at 630 +/- 3 nm increases local levels of skin
      homing T-cells in human subjects.
AB  - BACKGROUND AND AIMS: Red light phototherapy with laser sources has been used
      successfully for a number of indications. A new generation of quasimonochromatic
      630 +/- 3 nm light-emitting diode (LED) systems has recently been yielding good
      results for the same indications, but no study has examined changes in visible
      red light irradiated skin at an immunological level. This study was thus designed
      to examine changes in skin-homing T-cell levels induced in normal human skin by
      visible red LED energy. SUBJECTS AND METHODS: Six adult male volunteers (35
      approximately 48 years old) who satisfied all study criteria had the skin over
      the lateral aspect of the leg irradiated once per week for 8 weeks with a visible
      red (630 +/- 3 nm) LED-based system, with irradiance of 105 m/cm2, 15
      minutes/session, and a radiant flux of 94 J/cm2. Skin biopsies were performed
      after the eighth treatment session, and cultures were prepared to assay the type
      and quantity of skin-homing T-cells using qualitative and quantitative polymerase
      chain reaction (PCR) techniques. Ultrastructural changes were also assessed with
      transmission electron microscopy. RESULTS: Transmission electron microscopy
      revealed mild fibroplastic changes in fibroblasts, with no acute inflammatory
      changes throughout the treatment session. Qualitative PCR showed the presence of
      both Th-1 and Th-2 T-cells, and quantitative PCR showed an increase in the
      numbers of both types of skin-homing T-cells, much more so for Th-2 than for Th
      1. CONCLUSIONS: Visible red LED irradiation appears to activate the skin-homing
      immune system.

PMID- 16641532
TI  - Outcome of surgical treatment of synchronous liver metastases from colorectal
      cancer.
AB  - BACKGROUND: We retrospectively identified the prognostic factors in cases of
      synchronous liver metastases from colorectal cancer and established a clinical
      strategy at our institution. METHODS: One hundred eight patients with hepatic
      metastases from colorectal cancer underwent a first radical hepatic resection. Of
      these, 67 were diagnosed with hepatic synchronous metastases from colorectal
      primaries (S group) and 41 were diagnosed with metachronous metastases (M group).
      Hepatic lesions were diagnosed concurrently with the primary lesions in 45 of the
      67 patients in the S group. Of these 45 patients, 37 underwent synchronous
      hepatectomy (SH group) and 8 underwent metachronous hepatectomy (MH group).
      RESULTS: The overall 3-, 5- and 10-year survival rates were 51.4%, 41.6%, and
      30.9%, respectively. There were no significant differences between the S and M
      groups in overall survival. Univariate analysis of the S group revealed
      significant differences in survival based on tumor factor, pathological lymph
      node metastases of the primary tumor, and the tumor-free margin. There were no
      significant differences between the SH and MH groups in overall survival.
      CONCLUSIONS: Patients with synchronous liver metastases from colorectal cancer
      should undergo radical resection of the primary lesion and simultaneous
      hepatectomy with an adequate tumor-free margin as a standard surgical course.

PMID- 16641533
TI  - The treatment of refractory pneumothorax in diffuse panbronchiolitis by
      intravenous administration of coagulation factor XIII concentrate.
AB  - This case report presents a patient with advanced diffuse panbronchiolitis
      accompanied by chronic respiratory failure, marked cachexia, and refractory
      spontaneous pneumothorax. Because instillation of a pleurodesis agent and
      thoracoscopy were considered highly risky and invasive, we instead treated the
      patient with intravenous administration of a coagulation factor XIII concentrate,
      and the pneumothorax resolved. This case suggests refractory pneumothorax in a
      restrictive ventilatory disorder can be effectively treated with noninvasive
      intravenous administration of coagulation factor XIII concentrate.

PMID- 16641534
TI  - Transient thrombocytopenia after incompatible red blood transfusion in an infant
      girl with autoimmune hemolytic anemia.
AB  - We report on 5-month-old girl with severe autoimmune hemolytic anemia (hemoglobin
      2.9 g/dl, positive direct Coombs test) in whom thrombocytopenia developed after
      red blood cell transfusion. The platelet count was 62.1 x 10(4)/mm3 on admission
      and rapidly fell to 6.0 x 10(4)/mm3 rapidly after transfusion of incompatible red
      blood cells with intravenous predonisolone administration. No increased hemolysis
      or alloimmunization was observed after transfusion. The platelet count and
      hemoglobin levels gradually improved over 8 weeks with corticosteroid therapy. We
      suspect that the thrombocytopenia in our patient was transfusion-induced.

PMID- 16641535
TI  - Cholecystitis caused by infiltration of immature myeloid cells: a case report.
AB  - A 59-year-old man with myelodysplastic syndrome who was hospitalized for
      evaluation of fever and generalized fatigue had elevated levels of C-reactive
      protein and pancytopenia. A search for a site of infection and empiric treatment
      with antibiotics were unsuccessful. Over 5 to 6 weeks right upper quadrant pain
      and rebound tenderness developed. Sonographic Murphys sign was present. Computed
      tomography showed thickening of the gallbladder wall, and repeated
      ultrasonography demonstrated changes consistent with cholecystitis. Open
      cholecystectomy was performed as an emergency procedure. Macroscopically the
      resected gallbladder showed an edematous and thickened wall. Histopathologic
      examination revealed transmural infiltration by atypical mononuclear cells with
      distinct nuclei. The cells showed immunohistochemical staining for CD15,
      indicating myeloid lineage. By 10 days after surgery, counts of leukocytes and
      leukoblasts had markedly increased, reaching 36,700/microL and 76.0%,
      respectively. The blast crisis was thought to indicate progression from
      myelodysplastic syndrome to leukemia. The patient died of progressive disease 12
      days after surgery. We have described a rare case of acute cholecystitis caused
      by infiltration of immature myeloid cells to the gallbladder. An acute abdomen
      complicating hematologic disorders is life-threatening and requires prompt and
      appropriate treatment.

PMID- 16641536
TI  - Combined neuroendocrine cell carcinoma and adenocarcinoma of the gallbladder:
      report of a case.
AB  - A 58-year-old man with a chief complaint of epigastralgia was admitted to our
      hospital. Physical examination disclosed a large, firm mass in the right
      hypochondrium. Abdominal computed tomography confirmed thickening of the
      gallbladder wall and a 15 x 8 cm mass occupying almost all of the right lobe and
      medial segment of the liver. With a preoperative diagnosis of malignant
      gallbladder tumor infiltrating the liver, right hepatic trisegmentectomy was
      performed. Histopathologic examination showed atypical cells with small round to
      oval nuclei and sparse eosinophilic cytoplasm, proliferating in a solid and focal
      nesting pattern. Near this small cell proliferation was a focus of tubular
      adenocarcinoma that showed a zone of transition from the small cell
      neuroendocrine pattern. The small cells demonstrated immunohistochemical
      reactivity for chromogranin A. Electron microscopy disclosed neurosecretory
      granules 150 nm in diameter, representing dense round core vesicles, confirming a
      neuroendocrine cell lineage. The patient was diagnosed with neuroendocrine cell
      carcinoma combined with adenocarcinoma of the gallbladder. Tumor recurrence
      became evident 3 months after surgery, and he died 4 months after surgery.

PMID- 16641537
TI  - Two-generation reproductive toxicity studies in rats with extra parameters for
      detecting endocrine disrupting activity: introductory overview of results for
      nine chemicals.
AB  - Two-generation reproductive toxicity studies using rats of benzophenone, n
      butylbenzene, butyl benzyl phthalate, 2,4-dichlorophenol, dicychlohexyl
      phthalate, diethyl phthalate, 4-nitrotoluene, lindane and vinclozolin, were
      performed to investigate whether these chemicals have endocrine-mediated effects
      with the support of the Ministry of Economy, Trade and Industry and the Ministry
      of the Environment. Benzophenone exposure was via the diet at concentrations of
      0, 100, 450 or 2000 ppm, n-butylbenzene was administered orally by gavage at dose
      levels of 0, 30, 100 or 300 mg/kg/day, butyl benzyl phthalate was administered
      orally by gavage at dose levels of 0, 100, 200, or 400 mg/kg/day, 2,4
      dichlorophenol was administered in the diet at concentrations of 0, 500, 2000 or
      8000 ppm, dicyclohexyl phthalate was given in the diet at concentrations of 0,
      240, 1200 or 6000 ppm, diethyl phthalate was administered in the diet at
      concentrations of 0, 600, 3000 or 15000 ppm, 4-nitrotoluene was administered
      orally by gavage at doses of 0, 40, 80, or 160 mg/kg/day, lindane exposure was in
      the diet at concentrations of 0, 10, 60, or 300 ppm, and vinclozolin treatment
      was by feeding diet at concentrations of 0, 40, 200 or 1000 ppm.

PMID- 16641538
TI  - A two-generation reproductive toxicity study of 4-nitrotoluene in rats.
AB  - 4-Nitrotoluene (4-NT) was administered orally at doses of 0, 40, 80, or 160
      mg/kg/day by gavage to 24 Crj:CD (SD)IGS rats of each sex per group over two
      successive generations, and the effects on reproductive capacity in the parental
      animals and growth and development of the offspring were investigated. In the F0
      and F1 parents, increased hepatic and/or renal weights were observed at the doses
      of 40 mg/kg or more in both generations, with lowered body weights in the F1 case
      and reduced feeding efficiency, histopathological changes in the kidney and
      spleen at doses of 80 and 160 mg/kg, as well as worsening of clinical signs and
      death during the perinatal period at 160 mg/kg in both generations. With regard
      to effects on the reproductive capacity, reduced vaginal opening was observed at
      160 mg/kg in the F1 generation. However, no abnormalities were observed in the
      endocrine and reproductive organs or in serum hormone levels. In the F1 and F2
      offspring, decrease in body weight gain and brain weights was observed at the
      doses of 80 and 160 mg/kg and reduced viability, with elongation or a tendency
      for elongation of the male anogenital distance at 160 mg/kg. Thus, the
      possibility that 4-NT exerted endocrine disrupting effects seems to be very low
      under the conditions of this study, and when the substance was administered to
      rats over two generations, doses less than 160 mg/kg/day did not induce any
      marked adverse effects on the reproductive capacity in the parental animals, with
      the no observed effect level (NOEL) and the no observed adverse effect (NOAEL) on
      growth and development in the offspring concluded to be 40 mg/kg/day.

PMID- 16641539
TI  - Evaluation of a two-generation reproduction toxicity study adding endpoints to
      detect endocrine disrupting activity using lindane.
AB  - A two-generation reproduction toxicity study in rats adding extra endpoints to
      detect endocrine disrupting activity was conducted using lindane by dietary
      administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The
      extra endpoints included anogenital distance (AGD), nipple development, sexual
      maturation (vaginal opening and preputial separation), estrous cycle,
      spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and
      sex hormones). F1 offspring were examined for emotionality (open field test),
      motor coordination (rotarod test), as well as learning and memory (pole-climbing
      test). Hepatic drug-metabolizing enzyme activities were also measured. The
      results revealed general toxicological effects on parental animals, influence on
      reproductive function, and altered development of offspring; however, they did
      not demonstrate any distinct changes in the extra endpoints for detection of
      endocrine disrupting activity. Adult toxicity was observed in both F0 and F1
      animals, including suppressed body weight gain and reduced food consumption in
      both sexes, and deaths of females at 300 ppm. Convulsions and irritability were
      observed during the perinatal period in pregnant F1 females given 300 ppm.
      Pathological examination revealed increased liver weights and centrilobular
      hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and
      above; in addition, increased kidney weights and increased hyaline droplets in
      the proximal tubule epithelium, and basophilic renal tubules in males were noted
      at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1
      males and females and adrenal weights were increased in F1 males and females at
      300 ppm; however, no histological changes were observed, and manifestations
      suggesting endocrine disrupting activity related to these changes were lacking.
      Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in
      F1 males at 60 and 300 ppm, and decreases in T3 and/or T4 in both sexes and
      generations at 300 ppm were presumed to be secondary changes associated with the
      induction of hepatic drug-metabolizing enzymes. Blood hormone analysis revealed
      no changes in sex hormones attributable to lindane in males or females. Hepatic
      drug-metabolizing enzyme activities were increased dose-dependently from 10 ppm
      in both sexes and generations, with the rise in BROD activity being the most
      prominent. There were also increases in MROD, EROD, T-6beta-OH, and T4-UDP-GT
      activities (BROD >> EROD > MROD, T-6beta-OH, T4-UDP-GT). This suggests that while
      lindane most strongly induces CYP2B, it also upregulates a number of other drug
      metabolizing enzymes, such as CYP1A, CYP3A, and UDP-GT. As for effects on
      reproductive function, lack of maternal behavior, including lactation and
      retrieval behavior, and consequent total litter loss were observed in F1 dams at
      300 ppm. There were no effects of lindane on the estrous cycle, spermatogenesis,
      mating, fertility, pregnancy, or parturition. Neonatal toxicity was observed in
      both sexes and generations, including suppressed body weight gain at 60 and 300
      ppm, and decreased thymus and spleen weights without histological change at 300
      ppm. The postnatal survival rate in F2 offspring was decreased due to lack of
      maternal behavior in dams at 300 ppm.

PMID- 16641540
TI  - Evaluation of a two-generation reproduction toxicity study adding endpoints to
      detect endocrine disrupting activity using vinclozolin.
AB  - A two-generation reproduction toxicity study in rats adding extra endpoints to
      detect endocrine disrupting activity was conducted using vinclozolin by dietary
      administration at 0, 40, 200, and 1000 ppm, for investigation of its utility. The
      extra endpoints included anogenital distance (AGD), nipple development, sexual
      maturation (vaginal opening and preputial separation), estrous cycle,
      spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and
      sex hormones). Hepatic drug-metabolizing enzyme activities were also measured.
      The results revealed changes due to vinclozolin in the AGD, nipple development,
      sexual maturation, sex organ weights, and blood sex hormone concentrations in
      males of both parental animals and offspring, even at the lowest dose of 40 ppm,
      confirmed by results for the classical endpoints of histopathological examination
      at 200 ppm and mating at 1000 ppm. The effects on parental males included
      increased pituitary and testis weights, and decreased epididymis weights at 1000
      ppm in both generations, and decreased prostate and epididymis weights at 200 and
      1000 ppm and seminal vesicle weights at 1000 ppm in F1 males. Histopathological
      examination revealed hypertrophy of the basophilic cells in the pituitary at
      these two doses, and diffuse hyperplasia of the testicular interstitial cells and
      atrophy of the seminal vesicle mucosa at 1000 ppm in F0 and F1 males. In
      addition, F1 males demonstrated decrease in prostate fluid at 200 and 1000 ppm.
      Blood hormone analysis revealed increases in LH, FSH, testosterone, and DHT in F0
      and F1 males at 1000 ppm. General toxicological effects included suppressed body
      weight gain in F0 and F1 females and in F1 males, and reduced food consumption in
      F0 and F1 females at 1000 ppm. Histopathological examination revealed
      centrilobular hepatocellular hypertrophy in males at 200 and 1000 ppm and in
      females at 1000 ppm, increased lipid droplets in the adrenal zona fasciculata and
      zona glomerulosa in males at 200 and 1000 ppm and in females at 40 ppm and above,
      and hyperplasia of ovarian interstitial cells and vacuolation of lutein cells in
      females at 1000 ppm in both generations. Almost all the tissue changes were
      accompanied by changes in weights. Decreases in T3 and/or T4 were observed in
      both sexes and generations at 1000 ppm and in F0 females at 200 ppm. However,
      these were presumed to be secondary to induction of hepatic drug-metabolizing
      enzymes, activities being increased for a range of enzymes in both sexes and
      generations at 1000 ppm. Rise in BROD activity was the most prominent, suggesting
      that vinclozolin mainly induces CYP2B. As for effects on reproductive function, a
      marked decrease in the fertility index caused by male infertility was observed in
      F1 animals at 1000 ppm. However, no effects on spermatogenesis were seen in
      either F0 or F1 males. Since cleft prepuce and penile hypoplasia were observed in
      infertile males, it is probable that the cause of infertility in F1 males was
      related to morphological abnormalities in the external genitalia. Vinclozolin did
      not affect the estrous cycle, mating, fertility, pregnancy, parturition, or
      nursing behavior in either F0 or F1 females. In offspring, in addition to
      suppressed body weight gain in F1 males and females at 1000 ppm, neonatal
      toxicity caused by antiandrogen activity of vinclozolin was observed in F1 and F2
      males. Effects included shortened AGD in F1 males at 1000 ppm and in F2 males at
      200 and 1000 ppm, and nipple/areola remnants in F1 males at 200 and 1000 ppm and
      in F2 males at 40 ppm and above. In addition, decreased epididymis weights at
      weaning and morphological abnormalities of the external genitalia, including
      cleft prepuce, penile hypoplasia, and vaginal pouch, were seen in F1 and F2 males
      at 1000 ppm.

PMID- 16641541
TI  - A two-generation reproductive toxicity study of n-butylbenzene in rats.
AB  - N-butylbenzene (n-BB), which is suspected of having endocrine disrupting effects,
      was administered orally by gavage at dose levels of 0, 30, 100, and 300 mg/kg/day
      to groups of Crj: CD (SD) IGS rats (24 males and 24 females per group) over 2
      generations, and the effects on fertility of the parental animals and
      development/growth of the offspring were investigated. In the F0 and F1 parental
      animals, n-BB at the doses of 30 mg/kg/day and above increased the liver weights,
      and the doses of 100 and 300 mg/kg/day increased the kidney weights and caused
      histopathological changes in the liver and kidney. Moreover, the dose of 300
      mg/kg/day also increase adrenal gland weights and there was a tendency for
      inhibition of body weight gain. With respect to effects on fertility, no
      significant findings were noted in the F0 parental males and females.
      Furthermore, it was concluded that n-BB did not induce serious reproductive
      toxicity in the F1 parental animals and no effects on the endocrine system were
      recognized. In the F1 and F2 offspring, n-BB at 300 mg/kg/day increased the
      thymus weights.

PMID- 16641542
TI  - A two-generation reproductive toxicity study of butyl benzyl phthalate in rats.
AB  - A two-generation reproductive toxicity study with extra parameters was performed
      for Butyl benzyl phthalate (BBP). The compound was administered orally by gavage
      with the doses of 0, 100, 200, or 400 mg/kg/day to groups of 24 Crj:CD (SD)IGS
      rats of both sexes to confirm the utility of the protocol for identification of
      non-steroid chemicals with endocrine activity by ssessing effects on parental
      animals and offspring. Softening of the testes, diffuse atrophy of testicular
      seminiferous tubules, decreased spermatozoa and/or residual germ cells in the
      epididymal lumina were observed in the F1generation after doses more than 100
      mg/kg, lowering of the F1 epididymal weights at doses more than 200 mg/kg, along
      with low F0 epididymal weights, Leydig cell hyperplasia, residual germ cells in
      the epidimymal lumina, and low seminal vesicle weights, small testes and
      epididymes, partial aplasia or aplasia of the epididymes, and Leydig cell
      hyperplasia in the F1 generation with 400 mg/kg. With regard to effects on the
      reproductive capacity, F1 parents at the dose of 400mg/kg showed a reduced
      fertility index and delayed preputial separation of the penis. In the offspring,
      lowered body weights in the F1 case, and change in anogenital distance in the F1
      females and F2 males were observed at doses more than 100 mg/kg, with low splenic
      weights at 400 mg/kg in both generations. Thus, the utility of this protocol was
      confirmed. In the parental animals, the no observed effect level (NOEL) and the
      no observed adverse effect level (NOAEL) were less than 100 mg/kg/day, and no
      serious effects on the reproductive capacity were induced at doses less than 200
      mg/kg/day. The NOEL and NOAEL for the growth and development of offspring were
      concluded to be less than 100 mg/kg/day.

PMID- 16641543
TI  - A two-generation reproductive toxicity study of benzophenone in rats.
AB  - The reproductive toxicity of benzophenone (BZP) was evaluated in a two generation
      test in which male and female Sprague-Dawley (SD) rats, parental (F0) and first
      generation (F1), were exposed to BZP by feeding diet containing BZP at
      concentrations of 0 (control), 100, 450 or 2000 ppm. With regard to the effects
      of BZP on the F0 and F1 parental animals, inhibition of body weight gain and food
      consumption, significantly elevated renal weights, dilatation of the renal
      proximal tubules, and regeneration of the proximal tubular epithelium were
      recognized at doses of 450 ppm and 2000 ppm, along with an increase in hepatic
      weight and centrilobular hepatocytic hypertrophy, considered as vital adaptive
      changes, at the doses of 100 ppm or more. Obvious effects on the endocrine system
      and reproductive toxicological effects were not found even at the dose of 2000
      ppm in the F0 or F1 parent. There were no test substance related changes in the
      estrous cycle, reproductive capability, delivery and lactation, sperm parameters,
      serum hormone levels, or necropsy findings. As for effects on the offspring,
      inhibition of body weight gain was observed in both the F1 and F2 males and
      females of the 2000 ppm group. No effects of BZP treatment were recognized in the
      number of male and female F1 or F2 pups delivered, viability, anogenital distance
      (AGD), physical development, the results of reflex and response tests, or on the
      observation results of external abnormalities. From the present study of BZP
      administered to rats over two successive generations, the no observed effect
      level (NOEL) on the parental animals is concluded to be less than 100 ppm.
      Concerning the effects on the endocrine system and the reproductive toxicity in
      the parental animals, the NOEL is 2000 ppm. In terms of the effects on the
      offspring, the NOEL is considered to be 450 ppm.

PMID- 16641544
TI  - A two-generation reproductive toxicity study of 2,4-dichlorophenol in rats.
AB  - A two-generation reproductive toxicity study was conducted with 2,4
      dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting
      effects. Wistar-Hannover rats, 24/sex/group, were given diet containing 2,4-DCP
      at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of
      the test substance on parental animals and their offspring over 2 successive
      generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was
      apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and
      food consumption of females were lowered significantly during the treatment
      period. Effects on body weights and food consumption were more serious in the
      8000 ppm group, both males and females being significantly affected. Reproductive
      effects of the test substance were also observed in the 2000 and 8000 ppm groups
      dose-dependently. Observations included significantly increased uterine weights
      of F1 and/or F2 female weanlings and reduced numbers of implantation sites and
      live births of F1 parental females. These results suggest that 2,4-DCP has weak
      reproductive toxicity, possibly based on endocrine activity. However, the basic
      mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.

PMID- 16641545
TI  - A two-generation reproductive toxicity study of dicyclohexyl phthalate in rats.
AB  - The reproductive toxicity of dicyclohexyl phthalate (DCHP) was evaluated in a two
      generation test in which male and female Sprague-Dawley (SD) rats of parental
      (F0) and F1 generation were exposed to DCHP in the diet at concentrations of 0
      (control), 240, 1200 or 6000 ppm. With regard to the effects on the F0 and F1
      parental animals, changes included inhibition of body weight gain and food
      consumption, diffuse hypertrophy of hepatocytes, and hypertrophy of thyroidal
      follicular epithelial cells at the doses of 1200 ppm and 6000 ppm. The following
      changes were observed in the 6000 ppm group: increase weights of the liver and
      thyroid, increased hyaline droplets in the renal proximal tubular epithelium (F0
      and F1 males), reduction of prostatic weight (F1 males), and diffuse and/or focal
      atrophy of testicular seminiferous tubules (F1 males). In addition, slight
      prolongation of the estrous cycle was noted in the F0 females of the 6000 ppm
      group, along with reduced spermatid head counts in the testes (homogenation
      resistant spermatids) in F1 male receiving doses of 1200 ppm or 6000 ppm. It is
      thought that the prolonged estrous cycle was secondary to the suppression of body
      weight gain. There were no test substance related changes in clinical signs and
      reproductive capability (mating, fertility, gestation and birth index), or in
      data for the delivery and lactational periods, or serum hormone levels. With
      regard to effects on the offspring, inhibition of body weight gain was found in
      the F1 and F2 6000 ppm, and decrease of anogenital distance (AGD) and appearance
      of areola mammae were observed in the F1 male 6000 ppm and F2 male receiving
      doses of 1200 ppm or 6000 ppm. No effects of DCHP treatment on the offspring were
      observed on results of clinical signs, the number of the pups delivered, sex
      ratio, viability, physical development, reflex and response tests, external
      abnormalities, organ weights, or necropsy findings. From the present study of
      DCHP administered to rats over two-generations, the no observed effect level
      (NOEL) for effects on the parental animals including the endocrine system, is
      considered to be 240 ppm. With regard to the reproductive toxicological effects
      on the parental animals, the NOEL is 240 ppm for males and 1200 ppm for females.
      For offspring, the NOEL values are concluded to be 240 ppm for males and 1200 ppm
      for females.

PMID- 16641546
TI  - A two-generation reproductive toxicity study of diethyl phthalate (DEP) in rats.
AB  - A two-generation reproductive toxicity study was performed to evaluate the
      effects of diethyl phthalate on parental reproductive performance, including
      features of the endocrine system and development and growth of offspring at
      dietary dose levels of 0, 600, 3000 and 15000 ppm. In F0 and F1 parents, no
      treatment-related adverse effects were observed in clinical findings, body
      weights, food consumption, reproductive parameters, and gross or
      histopathological findings in any treated group. Increased liver weights and
      enhanced activities of metabolic enzymes were observed in F0 males at 15000 ppm.
      F0 males also exhibited an increase in the content of CYP3A2, a cytochrome P450
      isozyme, at 15000 ppm, and a decrease in the levels of serum testosterone at 3000
      and 15000 ppm, suggesting sex steroid metabolism might be changed. However, these
      were not considered adverse effects because the degree of change was too slight
      to affect the reproductive capability to produce progeny. Body weight gains
      before weaning were inhibited in F1 and F2 pups and vaginal opening was slightly
      delayed in F1 females at 15000 ppm. No changes were observed in the reproductive
      performance. Therefore, the no-observed-adverse-effect level (NOAEL) from this
      study is considered to be 15000 ppm for parental animals, and 3000 ppm for
      development and growth of the pups.

PMID- 16641547
TI  - Matrix metalloproteinases 21 and 26 are differentially expressed in esophageal
      squamous cell cancer.
AB  - Matrix metalloproteinase 21 (MMP-21) and MMP-26 (matrilysin-2) are the two newest
      members of the human MMP gene family that have both been suggested to play an
      important role in epithelial tumor progression and to be regulated via the Wnt
      signaling pathway. We studied their expression in 34 esophageal squamous cell
      carcinomas and non-neoplastic epithelium. MMP-21 protein was detected in cancer
      cells and inflammatory cells at the invasive front. Its expression was associated
      with invasion, inflammation, apoptotic and well-differentiated areas of the
      tumors, but not with cell proliferation. Unlike MMP-21, MMP-26 protein was
      already upregulated in incipient invasion and its expression associated with
      regions of low differentiation being more sporadic at the invasive front. MMP-21
      was detected basally in KYSE-30 and OE21 esophageal squamous cell carcinoma
      cells, while MMP-26 was absent. None of the several cytokines and matrices tested
      were capable of consistently upregulating MMP-21 or MMP-26 mRNA expression in
      these two cell lines. Our results suggest that during esophageal tumorigenesis,
      MMP-21 and MMP-26 have different, unique expression patterns both being tightly
      regulated and induced in the vicinity of inflammation. MMP-21 may provide a
      marker for differentiating tumor areas. The putative role of MMP-26 as a marker
      of dysplasia and incipient invasion warrants further studies.

PMID- 16641548
TI  - Squamous cell carcinoma antigen isoforms in serum from cervical cancer patients.
AB  - Squamous cell carcinoma antigen (SCCA) is a serological marker of squamous cell
      carcinomas (SCC). To study whether any of the SCCA isoforms would provide
      additional and more specific/sensitive clinical information than total SCCA,
      immunoassays specific for the different forms of SCCA (free SCCA2, total SCCA2,
      total SCCA1 and total SCCA) were developed. SCCA isoforms were determined before
      therapy and in follow-up samples from patients with cervical cancer and in serum
      samples from healthy females. Serum samples from patients with benign skin
      diseases (psoriasis and eczema) were also selected based on elevated SCCA levels.
      Rising levels of SCCA1 and SCCA2 were seen in patients with recurrence or
      progressive disease at the end of the study. The rise in SCCA2 was usually more
      prominent than that in SCCA1. The dominating serological form of SCCA was free
      SCCA2 both in healthy controls and in patients with cervical cancer. Both SCCA1
      and SCCA2 were elevated in serum from cervical cancer patients and followed the
      clinical course of the disease during therapy monitoring. SCCA2 did not show
      improved tumor specificity as compared to SCCA1. A larger study is however
      necessary to make firm conclusions.

PMID- 16641549
TI  - Antiangiogenesis and damaging blood flow by antisense vascular endothelial growth
      factor oligodeoxynucleotides to suppress lung cancers.
AB  - Angiogenesis plays a key role in the growth and metastasis of lung cancers, and
      vascular endothelial growth factor (VEGF) is one of the major angiogenic factors.
      The study aims to investigate whether phosphoro thioate-modified antisense VEGF
      oligodeoxynucleo tides (ASODN) formulated in cationic liposome could inhibit the
      growth of Lewis lung carcinoma (LLC) tumors by antiangiogenesis. The study
      demonstrated that ASODN downregulated the expression of VEGF in LLC cells at
      levels of protein and mRNA in vitro and in vivo. The conditioned media obtained
      from LLC cells treated with ASODN significantly inhibited the proliferation of
      bovine aortic endothelial cells. The ASODN therapy significantly suppressed the
      growth of established subcutaneous LLC tumors in mice by inhibiting angiogenesis
      and damaging the blood flow of tumors. In conclusion, our results suggest that
      ASODN targeting VEGF presents a potent therapeutic strategy to combat lung
      cancers.

PMID- 16641550
TI  - Involvement of chemokine receptor CCR6 in colorectal cancer metastasis.
AB  - Various chemokine receptors, namely CXCR4, CCR6 and CCR7, have recently been
      shown to be involved in the regulation of metastasis in malignant tumors.
      However, little is known about the role of these receptors in promoting tumor
      metastasis of colorectal cancer (CRC) to the primary site of CRC metastasis in
      the liver. To investigate this issue, we analyzed the expression of the chemokine
      receptors CXCR4, CCR6 and CCR7 in colorectal tumors and colorectal liver
      metastases. In the present study, 30 human cancer samples from colorectal tissue,
      30 human samples from colorectal liver metastases and the adjacent nontumorous
      liver tissues were screened using quantitative real-time PCR, Western blot
      analysis, histochemistry, microdissection and the enzyme-linked immunosorbent
      assay (ELISA). While an overexpression of all the chemokine receptors was found
      in CRC, in colorectal liver metastases only the chemokine receptors CXCR4 and
      CCR6 were significantly upregulated. Consequently, we investigated the expression
      of the corresponding ligands CXCL12/SDF1alpha, CCL20/MIP3alpha, CCL19/MIP3beta
      and CCL21/6Ckine in various organs, such as the stomach, esophagus, pancreas,
      colon and rectum, in comparison with their expression in the liver as the primary
      site of metastatic spread in CRC. We found that only CCL20 exhibits peak levels
      of expression in the liver, thus indicating that an increased production of CCL20
      may contribute to the selective recruitment of CCR6-expressing cancer cells in
      CRC. Furthermore, we could demonstrate that CRC patients who developed liver
      metastases express significantly more CCL20 and CCL21 in the liver in comparison
      with an unaffected control group. Therefore, our findings strongly suggest an
      association between CCL20/CCR6 expression in human CRC and the promotion of
      colorectal liver metastasis.

PMID- 16641551
TI  - Relation of gallbladder function and Helicobacter pylori infection to gastric
      mucosa inflammation in patients with symptomatic cholecystolithiasis.
AB  - BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by
      Helicobacter pylori (Hp) infection in patients with symptomatic gallstone
      disease. However, the additional pathogenetic role of an impaired gallbladder
      function leading to an increased alkaline duodenogastric reflux is
      controversially discussed. AIM: To investigate the relation of gallbladder
      function and Hp infection to gastric mucosa inflammation in patients with
      symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients
      with symptomatic gallstones were studied by endoscopy and Hp testing. METHODS:
      Gastritis classification was performed according to the updated Sydney System and
      gallbladder function was determined by total lipid concentration of gallbladder
      bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen
      patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No
      significant differences for bile salts, phospholipids, cholesterol, or total
      lipids in gallbladder bile were found between these three groups of patients.
      However, while only 1 out of 54 (<2%) patients with mild or no gastritis was
      found histologically positive for Hp, this infection could be detected in 14
      (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate
      to marked gastric mucosa inflammation in gallstone patients is mainly caused by
      Hp infection, whereas gallbladder function is not related to the degree of
      gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone
      patients seems to be of limited pathophysiological relevance.

PMID- 16641552
TI  - Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer
      cells.
AB  - BACKGROUND/AIM: Inhibition of cyclooxygenase-2 has been proposed to be a
      potential mechanism for the chemoprevention of gastrointestinal tumors by
      nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by
      which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer
      cell lines and its downstream signaling pathway. METHODS: Two gastric cancer cell
      lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and
      apoptosis. The involvement of mitogen-activated protein kinase and Akt
      kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were
      studied in the AGS cell line. RESULTS: SC236 treatment induced apoptosis in
      gastric cancer cells and caused activation of p38 and stress-activated protein
      kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor
      SB203580 and the dominant-negative stress-activated protein kinase/jun kinase
      both failed, while the constitutively active form of Akt/PKB was able to block
      SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of
      cytochrome c and activation of caspases. CONCLUSION: One of the pathways involved
      in SC-236-induced apoptosis in gastric cancer cells is through downregulation of
      Akt and then release of cytochrome c.

PMID- 16641553
TI  - Respiration under control of uncoupling proteins: Clinical perspective.
AB  - The term 'uncoupling protein' was originally used for the mitochondrial membrane
      protein UCP1, which is uniquely present in mitochondria of brown adipocytes,
      thermogenic cells that regulate body temperature in small rodents, hibernators
      and mammalian newborns. In these cells, UCP1 acts as a proton carrier activated
      by free fatty acids and creates a shunt between complexes of the respiratory
      chain and ATP-synthase resulting in a futile proton cycling and dissipation of
      oxidation energy as heat. Recent identification of new homologues to UCP1
      expressed in brown and white adipose tissue, muscle, brain and other tissues
      together with the hypothesis that these novel uncoupling proteins (UCPs) may
      regulate thermogenesis and/or fatty acid metabolism and furthermore may protect
      against free radical oxygen species production have generated considerable
      optimism for rapid advances in the identification of new targets for
      pharmacological management of complex pathological syndromes such as obesity,
      type 2 diabetes or chronic inflammatory diseases. However, since the
      physiological and biochemical roles of the novel UCPs are not yet clear, the main
      challenge today consists first of all in providing mechanistic explanation for
      their functions in cellular physiology. This lively awaited information may be
      the basis for potential pharmacological targeting of the UCPs in future.

PMID- 16641554
TI  - Infection: are we defining it accurately?

PMID- 16641562
TI  - Fighting infection in chronic wounds.

PMID- 16641563
TI  - Identifying the Charcot foot.

PMID- 16641564
TI  - National Provider Identifier: should wound care specialists apply?

PMID- 16641565
TI  - Kaposi sarcoma in patients with diabetes and wounds.

PMID- 16641566
TI  - Treating a nonhealing wound with negative pressure wound therapy.

PMID- 16641567
TI  - Skin fails too: acute, chronic, and end-stage skin failure.
AB  - OBJECTIVE: To identify what has been published in the literature about acute and
      chronic skin failure and to propose a working definition of this phenomenon.
      DESIGN: A systematic review of MEDLINE and CINAHL to determine what has been
      published in the literature on the topics of skin failure, acute skin failure,
      chronic skin failure, multiple organ failure, end-of-life skin deterioration, and
      pressure ulcers in hospice from 1984 to 2005. MAIN OUTCOME MEASURES: Published
      papers were reviewed for content related to acute, chronic, and end-stage skin
      failure. MAIN RESULTS: Seven articles were identified that referenced either
      acute, chronic, or end-stage skin failure. Additional information was identified
      that discussed the processes of acute and chronic skin failure and pressure
      ulcers in individuals in hospice care or at the end of life. Care considerations
      and dilemmas related to a curative versus palliative goal in wound healing were
      discussed. CONCLUSIONS: Minimal literature exists on skin failure, yet caregivers
      and the public must be aware of, assess for, and consider this phenomenon in
      their care. Based on this literature review, skin failure was defined by the
      authors as an event in which the skin and underlying tissue die due to
      hypoperfusion that occurs concurrent with severe dysfunction or failure of other
      organ systems. Skin failure can be categorized as acute, chronic, or end stage.
      Pressure ulcers, a type of skin death, frequently occur in persons with a heavy
      disease burden, especially those at or near the end of life, despite good care.

PMID- 16641568
TI  - Pressure redistribution strategies for the diabetic or at-risk foot: part I.

PMID- 16641570
TI  - Enteric nervous system disease and recovery, plasticity, and regeneration.

PMID- 16641572
TI  - Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN
      Committee on Nutrition.
AB  - This comment by the European Society for Paediatric Gastroenterology Hepatology
      and Nutrition (ESPGHAN) Committee on Nutrition summarizes available information
      on the composition and use of soy protein formulae as substitutes for
      breastfeeding and cows' milk protein formulae as well as on their suitability and
      safety for supporting adequate growth and development in infants. Soy is a source
      of protein that is inferior to cows' milk, with a lower digestibility and
      bioavailability as well as a lower methionine content. For soy protein infant
      formulae, only protein isolates can be used, and minimum protein content required
      in the current European Union legislation is higher than that of cows' milk
      protein infant formulae (2.25 g/100 kcal vs. 1.8 g/100kcal). Soy protein formulae
      can be used for feeding term infants, but they have no nutritional advantage over
      cows' milk protein formulae and contain high concentrations of phytate, aluminum,
      and phytoestrogens (isoflavones), which might have untoward effects. There are no
      data to support the use of soy protein formulae in preterm infants. Indications
      for soy protein formulae include severe persistent lactose intolerance,
      galactosemia, and ethical considerations (e.g., vegan concepts). Soy protein
      formulae have no role in the prevention of allergic diseases and should not be
      used in infants with food allergy during the first 6 months of life. If soy
      protein formulae are considered for therapeutic use in food allergy after the age
      of 6 months because of their lower cost and better acceptance, tolerance to soy
      protein should first be established byclinical challenge. There is no evidence
      supporting the use of soy protein formulae for the prevention or management of
      infantile colic, regurgitation, or prolonged crying.

PMID- 16641573
TI  - Amylase-resistant starch as adjunct to oral rehydration therapy in children with
      diarrhea.
AB  - BACKGROUND: Oral rehydration solution (ORS) for treatment of diarrhea relies on
      enhancement of small intestinal sodium and fluid absorption to correct
      dehydration. Amylase-resistant starch added to ORS significantly reduced the
      duration and severity of diarrhea in adults with cholera, presumably by
      generation of short-chain fatty acids in the colon and enhancement of colonic
      sodium and fluid absorption. The present study was initiated to determine whether
      addition of amylase-resistant starch to standard World Health Organization
      glucose-ORS (G-ORS) would reduce the duration of diarrhea and fecal fluid losses
      in children with acute diarrhea. METHODS: One hundred eighty-three children (6
      months to 3 years) with acute watery diarrhea were randomized to receive either
      standard treatment with G-ORS or G-ORS with additional amylase-resistant starch,
      HAMS (HAMS-ORS, 50g/L). Stool weight and consistency were monitored serially
      until development of formed stool or development of treatment failure defined as
      either the need for unscheduled intravenous fluid therapy or diarrhea longer than
      72 hours. RESULTS: Five of the subjects were lost to follow up. In 178 remaining
      children (87 HAMS-ORS and 91 G-ORS) with evaluable data, time from enrolment to
      last unformed stool was significantly less in children receiving HAMS-ORS
      (median, 6.75 hours; 95% confidence interval, 4.27-9.22) than in children treated
      with G-ORS (12.80 hours, 8.69-16.91) (P = 0.0292). Time to first formed stool was
      also significantly shorter in children receiving HAMS-ORS (median, 18.25 hours;
      95% confidence interval, 13.09-23.41) compared with children receiving G-ORS
      (median, 21.50 hours; 95% confidence interval, 17.26-25.74) (P = 0.0440). The
      total amount of ORS consumed was similar in both groups. There was a trend toward
      lower mean stool weight in first 24 hours (P = 0.0752) as well as total diarrheal
      stool weight (P = 0.0926) in patients in the HAMS group compared with the G-ORS
      group. CONCLUSION: In children with acute diarrhea, the addition of amylase
      resistant starch to glucose ORS significantly shortened duration of diarrhea
      compared with standard treatment.

PMID- 16641574
TI  - Long-term clinical outcome in patients with congenital chloride diarrhea.
AB  - OBJECTIVES: Congenital chloride diarrhea (CLD) is a rare, autosomal recessive
      disorder of intestinal Cl/HCO3 exchange caused by mutations in the SLC26A3 gene
      and characterized by persistent Cl rich diarrhea from birth. Treatment is
      symptomatic and replacement therapy with NaCl and KCl has been shown to be
      effective in children, but the long-term prognosis remains unclear. We studied
      the largest known cohort of patients to evaluate the long-term outcome of CLD and
      to search for extraintestinal manifestations. METHODS: This is a cross-sectional
      clinical evaluation and retrospective analysis of medical history of 36 Finnish
      patients with CLD, born in the 1960s (n = 8), 1970s (n = 7) and 1980s (n = 21).
      RESULTS: Early diagnosis and aggressive salt replacement therapy were associated
      with normal growth and development, in addition to significantly reduced
      mortality rates among the groups of patients born in the different decades,
      respectively (P = 0.001). No deaths due to CLD were observed after 1972.
      Enuresis, slight soiling and hospitalizations for gastroenteritis were common,
      especially in childhood, but 92% of the patients found their health excellent or
      good. Complications documented were end-stage renal disease (n = 1) and
      hyperuricemia (n = 4), novel findings possibly associated with CLD being male
      subfertility (n = 3), spermatoceles (n = 3), intestinal inflammation (n = 2),
      inguinal hernias (n = 4) and increased concentrations of sweat Cl in 12% of the
      patients. CONCLUSIONS: When early diagnosed and adequately treated, the long-term
      prognosis of CLD is favorable. A putative role of a primary anion exchange defect
      of SLC26A3 in male subfertility and the decline of renal function due to chronic
      dehydration deserve further characterization.

PMID- 16641575
TI  - Treatment of oesophageal bile reflux in children: the results of a prospective
      study with omeprazole.
AB  - OBJECTIVES: Reflux of duodenal juice into the oesophagus has a role in the
      pathogenesis of both oesophageal and laryngopharyngeal inflammatory and
      neoplastic lesions. As little is known about effective therapy, we studied the
      effect of proton pump inhibitor therapy on oesophageal bile reflux in children.
      METHODS: Twenty-nine children with moderate to severe erosive oesophagitis and
      abnormal oesophageal bile reflux were studied before and after treatment with
      omeprazole 1 mg/kg per day. Outcomes included a clinical symptom score,
      oesophageal acid and bile reflux (simultaneous 24-hour pH and Bilitec 2000
      monitoring), and mucosal healing. RESULTS: After 8 weeks of therapy, 17 (59%) of
      the patients were symptom-free, and 5 (17%) had minimal symptoms. Mucosal healing
      or reduction to low-grade oesophagitis was achieved in 25 children (86%; P <
      0.0005). Mean percentages of total, upright, and supine time with oesophageal pH
      less than 4 were reduced from 17.0%, 16.8%, and 19.2% before treatment, to 2.83%,
      3.17%, and 2.07%, respectively, after treatment (all P < 0.00001). Similarly,
      mean percentages of total, upright, and supine time with bile reflux were reduced
      from 16.96%, 12.67%, and 22.0%, to 2.27%, 1.91%, and 2.23%, respectively (P <
      0.000001, P < 0.0001, and P < 0.000001, respectively). CONCLUSIONS: Omeprazole 1
      mg/kg per day is an effective therapy for the majority of children with severe
      erosive oesophagitis due to abnormal isolated bile reflux or combined acid and
      bile reflux. It remains unclear how patients with treatment-resistant bile reflux
      should be managed.

PMID- 16641576
TI  - Multicenter, randomized, double-blind study comparing 10, 20 and 40 mg
      pantoprazole in children (5-11 years) with symptomatic gastroesophageal reflux
      disease.
AB  - OBJECTIVE: To evaluate symptom improvement in 53 children (aged 5-11 years) with
      endoscopically proven gastroesophageal reflux disease (GERD) treated with
      pantoprazole (10, 20 and 40 mg) using the GERD Assessment of Symptoms in
      Pediatrics Questionnaire. METHODS: The GERD Assessment of Symptoms in Pediatrics
      Questionnaire was used to measure the frequency and severity over the previous 7
      days of abdominal/belly pain, chest pain/heartburn, difficulty swallowing,
      nausea, vomiting/regurgitation, burping/belching, choking when eating and pain
      after eating. Individual symptom scores were based on the product of the
      frequency and usual severity of each symptom. The sum of the individual symptom
      score values made up the composite symptom score (CSS). The primary end point was
      the change in the mean CSS from baseline to week 8. RESULTS: Mean frequency and
      severity of each symptom significantly decreased (from P < 0.006 to P < 0.001)
      over time. Similar significant decreases in CSS at week 8 versus baseline (P <
      0.001) were seen in all groups. Significant decreases from baseline in CSS were
      noted from weeks 1 to 8 in the 20-mg (P < 0.003) and 40-mg (P < 0.001) groups.
      The 20- and 40-mg doses were significantly (P < 0.05) more effective than the 10
      mg dose in improving GERD symptoms at week 1. Adverse events were similar among
      the treatment groups. CONCLUSIONS: Pantoprazole (20 and 40 mg) is effective in
      reducing endoscopically proven GERD symptoms in children. Both 20 and 40 mg
      pantoprazole significantly reduced symptoms as early as 1 week.

PMID- 16641577
TI  - Variability of the 13C-acetate breath test for gastric emptying of liquids in
      healthy children.
AB  - PURPOSE: Scintigraphy is considered as the "gold standard" for measuring gastric
      emptying (GE). The C-acetate breath test (C-ABT) offers an attractive alternative
      to measure GE of liquids as it is nonradioactive. The aim of this study was to
      assess the variability of the C-ABT for GE of liquids in healthy children using
      nondispersive infrared spectrometry (NDIRS). METHODS: The C-ABT was repeated at
      least 2 times in 21 healthy children (6 girls and 15 boys), aged between 6.2 and
      16.4 years, 2 to 7 days apart. After an overnight fast, a standardized milk
      drink, labeled with 50 or 100 mg C-acetate according to weight, was administered.
      Breath samples were taken before feeding, at 5-minute intervals for the first 40
      minutes and at 10-minute intervals for the following 140 minutes after feeding.
      Breath samples were analyzed using NDIRS, and C recovery was used to calculate
      values for gastric half-emptying time (t1/2), time of peak C exhalation, or
      gastric lag phase (tlag) and gastric emptying coefficient (GEC). Intraindividual
      variabilities of the parameters t1/2, tlag, and GEC were expressed as coefficient
      of intrasubject variation (CV). RESULTS: The median CV of t1/2 was 8.3% (CV
      range, 1.6%-16.2%; t1/2 interindividual range, 65-112 minutes; and t1/2
      intraindividual range, 4-33 minutes). The median CV of tlag was 16.6% (CV range,
      2.0%-26.6%; tlag interindividual range, 31-76 minutes; and tlag intraindividual
      range, 1-35 minutes). The median CV of GEC was 4.3% (CV range, 0.8%-15.7%; GEC
      interindividual range, 3.81-4.89; GEC intraindividual range, 0.08-1.31). The CVs
      of t1/2, tlag, and GEC were independent of age, sex, weight, height, and measured
      values of t1/2, tlag, and GEC. CONCLUSIONS: The C-ABT using NDIRS is an easy,
      noninvasive, and nonradioactive procedure with a large intraindividual variation
      for measuring GE of liquids in healthy children, but comparable to the variation
      reported with other techniques.

PMID- 16641578
TI  - Natural history and symptomatology of Helicobacter pylori in childhood and
      factors determining the epidemiology of infection.
AB  - BACKGROUND: High seroprevalence rates for Helicobacter pylori have been reported
      in developing countries, yet few studies exist determining the pattern of change
      in the epidemiology of H. pylori infection in children. The knowledge of
      acquisition and loss rates of H. pylori and the relevance to the sociodemographic
      properties and the symptomatology of infection may provide clues for lifestyle
      changes that might protect children from infection, and also, it may provide
      rationale for eradication, screening, and protection policies. Our aim was to
      conduct a prospective study to elucidate the outcome, rate of acquisition, and
      loss of H. pylori infection in a population of healthy children. METHODS: This
      study is based on follow-up of 327 healthy Turkish children aged 3 to 12 years.
      The follow-up was conducted 6 years after the baseline examination. Helicobacter
      pylori status was determined by C-urea breath test. Children were investigated
      for sociodemographic variables and several symptoms. RESULTS: Data from 136 (41%)
      of 327 children were available. The prevalence of infection increased from 52.9%
      to 56.6%, mainly increasing in children younger than 10 years. The incidence of
      H. pylori infection among previously uninfected children was 14%, and the loss
      rate of infection among previously infected children was 5.5% during the follow
      up. Socioeconomic status, household density, and antibiotic use during last 6
      months were inversely related to H. pylori prevalence. Children infected with H.
      pylori were complaining more often of headache but not of abdominal pain or
      dyspepsia. CONCLUSIONS: In this study, the acquisition rate of H. pylori
      infection was 2.5-fold higher than the loss of infection, and the acquisition
      mostly occurred before 10 years of age. Data regarding acquisition and loss of H.
      pylori infection are critical for understanding the epidemiology of infection and
      development of preventive and treatment strategies.

PMID- 16641579
TI  - Systemic vasculitis: a cause of indeterminate intestinal inflammation.
AB  - OBJECTIVES: Indeterminate intestinal inflammation may result from a variety of
      inflammatory conditions in addition to ulcerative colitis and Crohn disease. The
      primary systemic vasculitides may present with intestinal inflammation and an
      indeterminate colitis. We set out to describe a series of children with primary
      systemic vasculitis who initially presented with clinical features suggestive of
      inflammatory bowel disease (IBD) to establish criteria that might help
      discriminate between IBD and primary systemic vasculitis. METHODS: Ten children
      (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied
      inclusion criteria. RESULTS: All had abdominal pain, weight loss, diarrhea (6 of
      10 bloody) and laboratory evidence of a severe acute phase response.
      Extraintestinal clinical features included vasculitic rash, renal impairment,
      myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or
      other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut
      histology revealed indeterminate chronic inflammatory mucosal changes and one
      patient with small artery fibrinoid necrosis in the submucosal vessels.
      Extraintestinal biopsy was performed in 6 patients and had a higher yield for the
      demonstration of vasculitis than intestinal biopsy. The results of selective
      visceral angiography was suggestive of vasculitis in all patients, but was normal
      in 7 cases of treatment-unresponsive classic IBD. Treatment comprised
      corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7
      of 10 patients. CONCLUSIONS: Extraintestinal manifestations and inflammatory
      responses that may be disproportionate to the degree of intestinal inflammation
      provide clues to the presence of an underlying primary systemic vasculitis, and
      these data suggest that selective visceral angiography plays a key role in the
      diagnosis of vasculitis in this context. It is important to identify and treat
      any vasculitic component because failure to do so may result in consequential
      morbidity or mortality.

PMID- 16641580
TI  - Exocrine pancreatic function in children with progressive familial intrahepatic
      cholestasis type 2.
AB  - In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe
      steatorrhea is often documented. However, pancreatic exocrine secretion has not
      yet been studied. In 14 children with PFIC-2, pancreatic function was assessed
      using standard fecal tests. Normal fecal lipase concentrations excluded isolated
      lipase deficiency. No differences in fecal elastase-1 concentrations and
      chymotrypsin activities were detected between PFIC-2 patients with or without
      steatorrhea, nor between these patients and healthy subjects. In conclusion,
      pancreatic exocrine function in patients with PFIC-2 is normal. Steatorrhea
      observed in those patients is not related to pancreatic insufficiency.

PMID- 16641581
TI  - Fractional calcium absorption is increased in girls with Rett syndrome.
AB  - BACKGROUND: Rett syndrome (RTT), an X-linked neurodevelopmental disorder
      primarilyaffecting girls, is characterized in part by osteopenia and increased
      risk of skeletal fractures. We hypothesized that decreased intestinal calcium
      (Ca) absorption relative to dietary Ca intake and increased renal Ca excretion
      might cause these problems in RTT. OBJECTIVE: We measured fractional Ca
      absorption, urinary Ca loss, dietary Ca intake, and the hormonal factors
      regulating Ca metabolism to determine whether abnormalities in Ca balance might
      relate to poor bone mineralization in RTT girls and to evaluate the contribution
      of these factors to the overall dietary Ca needs of RTT girls. STUDY DESIGN: Ten
      RTT girls and 10 controls, matched for age, sex, and pubertal status, were given
      a 3 day constant Ca diet that mimicked their habitual intakes. At the end of each
      dietary period, girls received single doses of Ca (intravenous) and Ca (oral).
      Fractional urinary excretion of Ca, Ca, 24 hour urinary Ca, and urinary cortisol
      excretion were determined. Serum Ca, phosphorous, alkaline phosphatase, vitamin D
      metabolites, parathyroid hormone (PTH), and osteocalcin were measured in the
      postabsorptive state. Bone mineral content (BMC) was measured by dual-energy x
      ray absorptiometry. RESULTS: Fractional Ca absorption was significantly higher in
      RTT than in control girls (mean +/- SDp, 52 vs. 33 +/- 13%). Dietary Ca intake
      (mean +/- SDp, 1,100 vs. 1,446 +/- 440 g/d) and net Ca absorption (mean +/- SDp,
      513 vs. 362 +/- 306 mg/d) did not differ significantly between RTT and controls,
      respectively. Although urinary Ca excretion did not differ between groups, the
      increased urinary Ca:creatinine ratio (mean +/- SDp, 0.39 vs. 0.23 +/- 0.38) was
      consistent with clinical hypercalcuria and paralleled the significantly increased
      urinary cortisol excretion (mean +/- SDp, 3.1 vs. 1.7 +/- 1.1 mg/kg lean body
      mass per day) in the RTT girls. BMC was significantly lower in RTT than in
      controls (mean +/- SDp, 527 vs. 860 +/- 275 g). Serum Ca, P, alkaline
      phosphatase, vitamin D metabolites, PTH, and osteocalcin concentrations did not
      differ between the groups. CONCLUSION: Fractional Ca absorption showed a
      compensatory increase in the presence of adequate dietary Ca intakes, mild
      hypercalcuria, and pronounced bone mineral deficits in RTT girls. Whether
      supplemental dietary Ca could enhance fractional Ca absorption and improve bone
      mineralization in RTT girls is unknown.

PMID- 16641582
TI  - Management of end-stage central venous access in children referred for possible
      small bowel transplantation.
AB  - The 3-year survival after small bowel transplantation (SBTx) has improved to
      between 73% and 88%. Impaired venous access for parenteral nutrition can be an
      indication for SBTx in children with chronic intestinal failure. AIM: To report
      our experience in management of children with extreme end-stage venous access.
      SUBJECTS: The study consisted of 6 children (all boys), median age of assessment
      27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis
      (1), protracted diarrhea (1), and short bowel syndrome (4), of which
      gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All
      had a documented history of more than 10 central venous catheter insertions
      previously. All had venograms, and 1 child additionally had a magnetic resonance
      angiogram to evaluate venous access. Five of 6 presented with thrombosis of the
      superior vena cava (SVC) and/or inferior vena cava. METHODS: Venous access was
      reestablished as follows: transhepatic venous catheters (5), direct intra-atrial
      catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of
      left subclavian vein after passage of a guide wire and then placing a catheter to
      reach the right atrium (1), radiological recanalization of the SVC and placement
      of a central venous catheter in situ (1), and direct puncture of SVC stump(1).
      Complications included serous pleural effusion after direct intra-atrial line
      insertion, which resolved after chest drain insertion (1), displacement of
      transhepatic catheter needing repositioning (2), and SVC stent narrowing
      requiring repeated balloon dilatation. OUTCOME: Four children with permanent
      intestinal failure on assessment were offered SBTx, 3 of which were transplanted
      and were established on full enteral nutrition; the family of 1 child declined
      the procedure. In the remaining 2 children in whom bowel adaptation was still a
      possibility, attempts were made to provide adequate central venous access as
      feeds and drug manipulations were undertaken. One of them received liver and SBTx
      nearly 3 years after presenting with end-stage central venous access, because
      attempts to achieve independence from parenteral nutrition had failed. The other
      child died immediately after a transhepatic venous catheter placement, possibly
      from a nutritional depletion syndrome as no physical cause of death was found.
      Direct intra-atrial catheters in transplanted children proved to be adequate for
      the management of uncomplicated transplantation, although the usual infusion
      protocol had to be modified considerably, and the lack of access would have been
      critical if massive blood transfusion had been required during the transplant
      procedure. CONCLUSION: It was possible to reestablish central venous access in
      all cases. However, this was time consuming and difficult to assemble a skilled
      team consisting of one of more: surgeon, cardiologist, interventional
      radiologist, and transplant anesthetist. Small bowel transplantation is easier
      and safer with adequate central venous access, and we advocate liaison with an
      SBTx center at an early stage.

PMID- 16641583
TI  - Chronic diarrhea as first manifestation of liver cirrhosis and hepatocarcinoma in
      a teenager: a case report and review of the literature.

PMID- 16641584
TI  - Indwelling balloon dilatation for esophageal stenosis in infants.

PMID- 16641585
TI  - Intrahepatic biliary cysts presenting before hepatic portoenterostomy in biliary
      atresia.

PMID- 16641586
TI  - Complications associated with endoscopic removal of percutaneous endoscopic
      gastrostomy (PEG) tubes in children.

PMID- 16641587
TI  - Oral probiotics prevent necrotizing enterocolitis.

PMID- 16641588
TI  - Duodenal diverticulum.

PMID- 16641589
TI  - Congenital syphilis.

PMID- 16641590
TI  - Registry of randomized controlled trials in transplantation: January 1 to June
      30, 2005.

PMID- 16641591
TI  - Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation as a
      late complication of chronic graft-versus-host disease.
AB  - BACKGROUND: This study aims to determine the incidence and outcome of nephrotic
      syndrome in patients who underwent allogeneic stem cell transplantation in a
      single center. METHODS: Records of 279 adult patients with hematological diseases
      who underwent allogeneic hematopoietic stem cell transplantation were analyzed to
      evaluate the incidence and outcome of nephrotic syndrome. The diagnosis of
      chronic graft-versus-host disease was based on clinical evidence with
      histological confirmation whenever possible. RESULTS: Of the 279 patients, 105
      with a minimum follow-up of 100 days developed chronic graft-versus-host disease:
      six of these had nephrotic syndrome. The cumulative incidence of nephrotic
      syndrome was 8% at day +1,681. Patients grafted with peripheral blood stem cells
      had a higher probability of developing nephrotic syndrome than did those grafted
      with bone marrow: 24% and 3%, respectively. The pathological diagnosis was
      membranous glomerulonephritis in four patients, and minimal change disease in
      one; the diagnosis could not be histologically confirmed in the sixth patient.
      All patients had extensive chronic graft-versus-host disease and were receiving
      treatment with cyclosporine A and steroids (four patients). Response to
      immunosuppressive therapy with cyclosporine A and steroids was achieved in all
      patients at a median time of 12 weeks after transplantation. CONCLUSION: Patients
      with chronic graft-versus-host disease may be considered to be at risk of
      nephrotic syndrome: careful monitoring of renal function is advisable,
      particularly in patients receiving allogeneic peripheral stem cell grafts.

PMID- 16641592
TI  - Subsequent skin cancers in kidney and heart transplant recipients after the first
      squamous cell carcinoma.
AB  - BACKGROUND: The increased incidence of skin cancers in transplant patients is
      well documented; however, few data exist on the risk of subsequent skin tumors in
      a given patient after the first skin cancer. The aim of this study was to compare
      the individual rate of subsequent skin cancers in kidney (KTR) and heart
      transplant recipients (HTR) after the first squamous cell carcinoma (SCC) and to
      assess risk factors for tumor multiplicity. METHODS: In all, 188 patients (121
      KTR/67 HTR) were studied for up to 5 years. The cumulative number of SCC, basal
      cell carcinomas, Bowen's diseases, premalignant keratoses, and keratoacanthomas
      was recorded yearly after the first SCC. RESULTS: Overall, 71% of patients
      developed 757 new skin tumors. At 5 years, 100% of HTR and 88% of KTR had
      presented new tumors. However, the mean number of all tumors was significantly
      higher in KTR (3.4 vs. 2.0, 4.8 vs. 2.6, 6.6 vs. 2.9, 8.5 vs. 3.5, and 9.7 vs.
      4.6 at 1, 2, 3, 4, and 5 years, respectively). Transplantation before 1984,
      multiple tumors at first consultation, eye and hair color, and skin type were
      predictive of multiple tumors. Early minimization of immunosuppression and of sun
      exposure tended to be associated with a reduced rate of all tumors and of SCC,
      respectively. CONCLUSIONS: Although the proportion of HTR developing new tumors
      is greater as compared with KTR, the mean number of tumors per patient is higher
      in KTR. This could be due to a longer immunosuppression in patients younger at
      transplantation.

PMID- 16641593
TI  - Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.
AB  - BACKGROUND: This study aims to determine the impact of thymoglobulin-sirolimus
      cyclosporine immunosuppression on the alloimune response of pancreas-kidney
      transplant recipients. METHODS: Thirty-six pancreas transplant recipients
      received an induction protocol of thymoglobulin, sirolimus, reduced-dose
      cyclosporine, and corticosteroids. Ten recipients were also enrolled in a study
      to measure immune responsiveness. Flow PRA determined HLA antibody, donor
      specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell
      assays were performed during the first posttransplant year. RESULTS: One-year
      patient, kidney, and pancreas graft survivals were 97%, 94%, and 92%,
      respectively. There was one death and three graft losses. There were no acute
      rejection episodes. Recipients in the immune-monitoring study (n=10)
      displayed>80% depression of CD3, CD4, and CD8 (+) cell counts up to 3 months
      posttransplant. At transplantation 9/10 patients displayed<10% class I and no
      class II HLA antibody. By 3 months, 7/10 monitored recipients showed a transient
      elevation in class I HLA antibodies, including 2 patients who expressed>80% Flow
      PRA. One patient was pretransplant FCXM positive, whereas by 3 months
      posttransplant 2/10 patients demonstrated a positive FCXM. There were no clinical
      consequences of the presence of HLA antibody or the positive FCXMs. By 6 months,
      7/9 patients demonstrated immunoregulatory suppressor cells. CONCLUSIONS: The
      absence of acute rejection events was likely due to inhibition of donor-specific
      immunity by the immunosuppressive regimen. Seventy percent of patients
      demonstrated an early, non-donor-directed HLA antibody response that had no
      adverse effect on graft function and 78% of the monitored patients displayed
      immunoregulatory cells probably contributing to the successful outcomes.

PMID- 16641594
TI  - 24-week oral ganciclovir prophylaxis in kidney recipients is associated with
      reduced symptomatic cytomegalovirus disease compared to a 12-week course.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is associated with reduced graft and
      patient survival among kidney recipients. The highest risk of CMV infection
      occurs in CMV-naive recipients of kidneys from seropositive donors (D+/R-).
      Optimal CMV prophylaxis is not established. This prospective cohort study
      compared the safety and efficacy of prophylaxis with 12 versus 24 weeks of oral
      ganciclovir. METHODS: We prospectively administered 24 weeks ganciclovir to 31
      D+/R- recipients. The control group comprised 39 patients transplanted in the
      immediately preceding era who received a 12-week course of prophylaxis. All
      patients received cytolytic therapy within the first month, as well as a
      tacrolimus-based maintenance regimen. A logistic regression model was fit to
      examine the relationship between 24 weeks ganciclovir prophylaxis and the odds of
      developing CMV infection by one year. RESULTS: Groups were matched, though the 12
      week cohort had more delayed graft function than their 24-week counterparts (45%
      vs. 29%, P=0.04). CMV infection occurred in 31% and 7% patients in the 12-week
      and 24-week groups, respectively (P<or=0.01). Mean time to development of CMV
      infection was 17.5+/-2.2 weeks in the 12-week, and 22.0+/-10.0 weeks in the 24
      week, groups (P=0.79). Both 24 weeks ganciclovir prophylaxis (O.R. 0.15, 95% C.I.
      0.03-0.91, P=0.04) and delayed graft function (O.R. 4.49, 95% C.I. 1.67-36.56,
      P<0.01) were associated with CMV infection. CONCLUSIONS: Oral ganciclovir
      prophylaxis for 24 weeks is associated with a lower risk of symptomatic CMV
      disease than a 12-week course in high risk D+/R- kidney recipients.

PMID- 16641595
TI  - Posttransplantation anemia in adult renal allograft recipients: prevalence and
      predictors.
AB  - BACKGROUND: Management of anemia is an important factor in the care of patients
      with chronic kidney disease as the anemic state can confer significant morbidity
      and mortality. Posttransplantation anemia (PTA) has received comparatively less
      attention in the literature, and the prevalence and predictors of PTA vary
      between different studies. The purpose of this study was to investigate a large
      posttransplant population from 3 centres in the UK to elucidate the point
      prevalence of PTA, its determinants and the use of erythropoiesis stimulating
      agents (ESA) in these patients. METHODS: All adult patients with functioning
      renal transplants and attending renal transplant outpatients at Guy's, King's
      College, or St. Helier Hospitals, London, as of 31/12/2004 who had a valid
      hemoglobin in the previous 3 months, and who were more than 3 months
      postengraftment, were identified. Patients' notes and electronic patient records
      were obtained and a detailed cross-sectional clinical and biochemical database
      was constructed. The data were analyzed for the point prevalence of PTA, the
      prevalence of ESA use and for determinants of hemoglobin. The WHO criteria were
      used to define anemia and all patients on treatment with an ESA was classified as
      anemic irrespective of hemoglobin. RESULTS: A total of 1,511 (947 male) patients
      were studied. Mean age was 48.1+/-13.7 years with no difference between the
      sexes. Mean time posttransplantation was 8.5+/-7.2 years and mean estimated MDRD
      GFR was 47.6+/-18.9 ml/min with a higher GFR in males (49.9+/-19.0 v 43.8+/-18.0
      mL/min, P<0.0001). Mean hemoglobin in the studied population was 12.9+/-1.6 g/dl
      with a significantly higher level among males than females (mean 13.3+/-1.6 v
      12.3+/-1.4 g/dl, P<0.0001). The prevalence of anemia was 45.6% with a prevalence
      of 44.1% among males and 48.1% amongst females. Severe anemia was present in 50
      subjects (3.3% of the total cohort). One hundred and forty-five patients (9.6% of
      the entire cohort) were being treated with an ESA. Of these subjects, 41 did not
      meet WHO criteria for the definition of anemia. After multiple regression
      analyses, age, female sex, renal function and to a lesser extent serum ferritin
      and therapy with angiotensin converting enzyme inhibitors/angiotensin II receptor
      blockers (both negatively associated) were predictive of hemoglobin. CONCLUSIONS:
      The prevalence of anemia posttransplantation was high while comparatively few
      patients were being treated with erythropoiesis stimulating agents. The strongest
      predictors of hemoglobin in this cohort of patients were age, female sex and
      allograft function. Medical therapy with MMF and sirolimus was associated with a
      high prevalence of anemia but this was likely to be the result of poorer graft
      function in these subjects who mostly had chronic allograft nephropathy. A large
      interventional prospective study with valid control groups is now needed to
      assess the long-term contributions of clinical and biochemical factors of renal
      function and to elucidate the effects of therapy on outcome.

PMID- 16641596
TI  - Preemptive versus Non-preemptive simultaneous pancreas-kidney transplantation: a
      single-center, long-term, follow-up study.
AB  - BACKGROUND: Data regarding the timing-before or after initiation of dialysis-of
      simultaneous pancreas-kidney transplantation (SPKT) in type 1 diabetes mellitus
      patients with end-stage renal failure are sparse. We studied the effect of
      preemptive transplantation on patient survival, cardiovascular endpoints, and
      graft survival, as compared with non-preemptive transplantation. METHODS: All 180
      SPKT recipients (aged 23-58 years) who received a SPKT in Leiden between December
      1986 and May 2004 were included in the analysis. Sixty-five patients (36.1%) were
      transplanted preemptively. Mean follow-up time was 6.3 years. RESULTS: Up to 8.2
      years after transplantation, we found no differences in patient survival. Later
      on, divergence occurred: 10-year patient survival was 71.3% in the preemptive
      group versus 63.8% in the dialysis group and 15-year patient survival was 64.8%
      versus 45.1% in the dialysis group, leading to an adjusted hazard ratio for
      mortality of 0.50 (95% CI 0.23-1.06, P=0.070). Cause of death was less often of
      cardiac origin in the preemptive group (adjusted HR 0.16; 95% CI 0.026-0.95,
      P=0.044). Graft survival did not follow the same trend. No significant
      differences were found between the two groups considering allograft survival,
      cerebrovascular accident, or myocardial infarction. The percentage of patients
      with minor or major amputation(s) after transplantation was slightly lower in the
      preemptive group (24.6 vs. 32.1%; adjusted HR 0.87; 95% CI 0.42-1.82, P=0.72).
      CONCLUSION: Preemptive SPKT offered a patient survival benefit as compared with
      transplantation performed while already on dialysis and was associated with a
      lower rate of cardiac deaths.

PMID- 16641597
TI  - Perforin, Granzyme B, and fas ligand for molecular diagnosis of acute renal
      allograft rejection: analyses on serial biopsies suggest methodological issues.
AB  - BACKGROUND: The Perforin-Granzyme B and Fas/Fas Ligand apoptotic mechanisms are
      involved in the development of acute renal rejection (AR). We describe our
      experience of analyzing the expression of cytotoxic T-lymphotoxins (CTL) in
      biopsies and peripheral blood leukocytes (PBL) for the diagnosis of AR. METHODS:
      We analyzed Perforin (P), Granzyme B (GB) and Fas Ligand (FL) expression in 68
      renal biopsies and 64 PBL using comparative kinetic RT-PCR and, for GAPDH and FL,
      we also replicated with real-time RT-PCR. The levels of expression were measured
      in different groups, such as T0 (biopsies before reperfusion and PBL in recipient
      before the transplant [Tx]), Td (biopsies and PBL collected for clinical
      purposes) and Tp (biopsies and PBL two months after Tx). RESULTS: A higher CTL
      expression was seen in non-rejecting (NR) biopsies in the first 2 months after
      Tx. P and FL were significantly more expressed during AR in all biopsies and in
      Td, while P remained upregulated in Tp. In PBL, there was no significant increase
      in CTL transcription during AR. A variable expression of CTL emerged in all T0
      biopsies. CONCLUSIONS: Two lytic pathways are activated in biopsies when AR
      occurs shortly after Tx, whereas the P/GB mechanism prevails if it occurs later
      on. Only P and FL in biopsies might be able to predict AR diagnosis, but with a
      considerable variability in each sample, possibly due to the small portion of
      tissue core, which may be inadequate for molecular diagnosis. CTL expression in
      PBL does not correlate with histological AR.

PMID- 16641598
TI  - The importance of analyzing graft and patient survival by cause of failure: an
      example using pediatric small intestine transplant data.
AB  - BACKGROUND: Although graft and patient survival are vital in reporting overall
      results of clinical transplant studies, these outcomes do not account for
      distinct types of graft failure and death, which clearly exist in pediatric small
      intestine transplantation (Itx). The use of a cause-specific hazard (CSH)
      approach may provide more precise identification and thus greater insight as to
      why certain factors are prognostically important. METHODS: Among 119 pediatric
      patients who received primary Itx at our center since 1994, Cox model stepwise
      regression analyses were performed to identify prognostic factors for the
      following CSH rates: intestinal graft failure (IGF)/death due to rejection, death
      due to infection not triggered by IGF, and intestinal graft loss/death due to
      other causes. RESULTS: Two factors were associated with a significantly higher
      rate of developing IGF due to rejection (23 such failures): receiving an isolated
      intestine or liver-intestine transplant (P=0.00001) and receiving no induction
      agent (P=0.006). Conversely, age at transplant <1 year was the single factor
      associated with a significantly higher death rate due to infection (P=0.0005) (21
      such deaths). Two characteristics were associated with a significantly higher
      death rate due to other causes: being in the hospital pretransplant (P=0.007) and
      not receiving daclizumab induction therapy (P=0.02) (24 such deaths). Although
      these four factors (transplant type/age/hospital status/induction therapy) were,
      for the most part, associated with graft/patient survival, the CSH analysis more
      precisely identified their prognostic value and achieved greater statistical
      power. CONCLUSIONS: A CSH approach should be used in conjunction with overall
      outcome analyses.

PMID- 16641599
TI  - High incidence of gastric bezoars in cystic fibrosis patients after lung
      transplantation.
AB  - BACKGROUND: Bezoars are concretions of ingested matter which accumulate in the
      gastrointestinal tract and manifest as symptomatic foreign bodies. The aim of
      this study is to evaluate the incidence of gastric bezoars after lung
      transplantation and identify associated risk factors. METHODS: We performed a
      retrospective analysis of patients who underwent lung transplantation from
      December, 1992 through July, 2005 at our tertiary care medical center. Patients
      who had endoscopically confirmed gastrointestinal bezoars in the posttransplant
      setting were identified and compared with patients without bezoars. RESULTS: Of
      the 215 patients who received lung transplantation, 17 (7.9%) developed gastric
      bezoars confirmed by upper endoscopy. Cystic fibrosis was the leading indication
      for lung transplantation (n=145), and 11% of cystic fibrosis patients (16 of 145)
      formed gastric bezoars after transplant. Additionally, 94% of patients with
      bezoars (16 of 17) had cystic fibrosis (P=0.02), with the exception being a
      subject with primary ciliary dyskinesia. No patient who underwent lung transplant
      for another indication was found to have a bezoar. The mean time to diagnosis was
      34 days, with two-thirds of bezoars diagnosed within one month after transplant.
      The annual incidence was unchanged during the study period. CONCLUSIONS: Gastric
      bezoars are common in cystic fibrosis patients after lung transplantation. The
      etiology is likely multifactorial, related to gastric motility, respiratory
      secretions, and medications. Further investigation is needed to understand the
      pathogenesis of bezoar formation in this selected population, and strategies for
      primary prevention may be beneficial.

PMID- 16641600
TI  - Access to kidney transplantation in France of non-French patients and French
      patients living in overseas territories.
AB  - BACKGROUND: In France, foreign patients, whether resident or not in France, can
      register on the national waiting list under certain conditions. We compared
      waiting time to kidney transplantation, the level of HLA matching and graft cold
      ischemia time between foreign patients and French patients living in mainland
      France or in French overseas territories (FOT). METHODS: We performed a
      retrospective cohort survey using the nationwide registry. Between 1996 and 2003,
      18,595 patients were registered on the French waiting list. Of these, 9.9% were
      of non-French nationality (0.7% Greek, 1.4% Italian, 1.5% other European, 3.7%
      North African, 1.8% sub-Saharan African and 0.9% other), and 3.8% were French
      nationals living in FOT. RESULTS: Median waiting time differed significantly
      between groups, from 13.8 months for mainland French patients to 39.5 months for
      sub-Saharan African patients. After adjustment for other factors significantly
      linked to waiting time, French residents of FOT (RR=0.83; P<0.001) and patients
      from sub-Saharan Africa (RR=0.75; P<0.0001) were found to wait significantly
      longer than other patients. HLA matching level, particularly HLA-A and HLA-B, was
      worse for African patients. After adjustment for the transplant team, cold
      ischemia time was found to be longer for Greeks (30.4 hr, P<0.0001) and French
      patients living in FOT (33.3 hr, P<0.0001) than for mainland French patients
      (21.2 hr). CONCLUSIONS.: Programs promoting organ donation aimed at minorities of
      African origin should improve their access to transplantation in France. We also
      need to strengthen international cooperation programs in certain countries to
      assist access to transplantation and to increase graft quality.

PMID- 16641601
TI  - Prognostic values of soluble CD30 and CD30 gene polymorphisms in heart
      transplantation.
AB  - Pretransplant soluble CD30 (sCD30) is a predictor of kidney graft outcome. Its
      status as a predictor of heart transplant (HT) outcome has not been established.
      We have studied this question by assessing sCD30 levels and the number of (CCAT)n
      repeats of the microsatellite in the CD30 promoter region, which is able alone to
      repress gene transcription, in the sera of 83 HT patients and 77 of their donors.
      sCD30 was non-significantly increased in the patients, whereas there were no
      differences in the CD30 microsatellite allele frequencies. A negative correlation
      between the number of (CCAT)n and sCD30 levels was evident in the donors.
      Patients with pretransplant sCD30<or=30 U/ml displayed a significantly better
      survival. In conclusion, sCD30 levels are predictive of HT outcome.

PMID- 16641602
TI  - Depletion of pulmonary intravascular macrophages prevents hyperacute pulmonary
      xenograft dysfunction.
AB  - BACKGROUND: Recent years have brought dramatic progress in the field of
      xenotransplantation, with the development of transgenic swine and various other
      means of overcoming the rejection mediated by xenoreactive antibodies. Although
      progress has been rapid with kidney and heart xenografts, progress with pulmonary
      xenografts has lagged behind. Recent findings have suggested that donor pulmonary
      intravascular macrophages may play a critical role in the hyperacute dysfunction
      of pulmonary xenografts. METHODS: The function of pulmonary xenografts from pigs
      depleted of pulmonary intravascular macrophages was compared with the function of
      xenografts from normal pigs. RESULTS: Pulmonary xenografts from pigs from which
      pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours)
      about five times longer than normal (macrophage sufficient) xenografts (4.4+/
      1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary
      arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular
      macrophages, whereas all normal xenografts had failed. CONCLUSIONS: These
      findings indicate that donor macrophages play a critical role in pulmonary
      xenograft dysfunction. This finding has broad implications for
      xenotransplantation, suggesting that porcine macrophages might pose a barrier to
      the engraftment and function of a variety of porcine organ xenografts.

PMID- 16641603
TI  - Simian parvovirus infection in cynomolgus monkey heart transplant recipients
      causes death related to severe anemia.
AB  - BACKGROUND: Simian parvovirus (SPV) was first isolated from cynomolgus monkeys.
      Like human parvovirus B19, this virus has a predilection for erythroid cells.
      During acute SPV infection, clinical signs are usually mild or inapparent, but
      severe anemia may occur in immunocompromised animals. We report several cases of
      symptomatic SPV infection in cynomolgus monkeys following heart transplantation.
      METHODS: Twenty-three consecutive abdominal heterotopic heart transplants were
      studied. Viremia, measured by dot blot and/or PCR, and SPV-specific antibodies
      were determined retrospectively. RESULTS: All except one animal were on an
      immunosuppressive protocol. In all, 48% (11/23) of transplant recipients had
      viremia with SPV detected at some point after transplant. An additional 22%
      seroconverted before or after transplant, and were asymptomatic without
      detectable SPV. Of the 11 acutely viremic animals, five were euthanized because
      of severe anemia attributed to SPV. The remaining 30% of the transplant
      recipients did not seroconvert and were asymptomatic. Of seven recipients of
      donor tissue from seropositive or viremic animals, five became viremic and three
      died with anemia. No immunosuppressive regimen was implicated in increased
      susceptibility; the one transplant recipient not treated with immunosuppressive
      agents died with anemia and acute viremia two weeks after explant of a rejected
      graft. CONCLUSION: SPV is an important pathogen in surgically manipulated
      cynomolgus monkeys, particularly with immune compromise. Once introduced into a
      colony, clinically silent SPV infection could be readily transmitted within the
      environment. Transmission and disease occur at high frequency with an organ from
      a PCR-negative, seropositive donor, suggesting that latent virus can be conveyed
      by the organ.

PMID- 16641604
TI  - CD4+ T-cell-independent rejection of corneal allografts.
AB  - BACKGROUND: Several studies suggest that a significant number of corneal
      allografts undergo rejection in the absence of CD4 T cells. This study examined
      the role of CD4 T cell-independent mechanisms of corneal allograft rejection.
      METHODS: BALB/c corneal allografts were transplanted to C57BL/6 beige nude mice
      that received either CD8 or CD8 T cells from C57BL/6 CD4 knockout (KO) mice that
      had rejected BALB/c corneal allografts. Immune effector functions of CD8 or CD8 T
      cells from C57BL/6 CD4 KO mice were assessed using delayed-type hypersensitivity
      assays and Annexin V apoptosis assays respectively. RESULTS.: Both CD8 and CD8 T
      cells from CD4 KO corneal allograft rejector mice mediated corneal allograft
      rejection following adoptive transfer to nude mice. CD8 T cells, but not CD8 T
      cells, from CD4 KO mice adoptively transferred donor-specific DTH and induced
      apoptosis of BALB/c corneal endothelial cells in vitro. Apoptosis of BALB/c
      corneal endothelial cells was mediated by double negative (DN) T cells, as
      treatment of CD8 cells from CD4 KO mice with anti-Thy 1.2 plus complement
      abolished their effector function. CONCLUSION: The results support the
      proposition that CD4 T cell-independent rejection of corneal allografts can be
      mediated by either CD8 or CD8 T cells. The CD8 T cells represent a unique DN T
      cell population that might mediate rejection by either direct cytolysis or by
      inducing apoptosis of the donor corneal endothelium.

PMID- 16641605
TI  - "Firefly rats" as an organ/cellular source for long-term in vivo bioluminescent
      imaging.
AB  - BACKGROUND: Transplantation research involving the use of stem cells demands an
      appropriate in vivo visualization system to monitor cellular fate over an
      observation period. The new field of in vivo imaging is being developed with
      fluorescent and luminescent biotechnology, and involves the real-time
      visualization of complex cellular processes in living animals. METHODS: :
      Following our recent development of inbred green fluorescent protein (GFP)
      transgenic (Tg) rats, we created the establishment of inbred (Lewis) Tg rats with
      firefly luciferase. The immunogenicity against luciferase was evaluated by the
      skin grafting test, and the fate of grafts was monitored by in vivo luminescent
      technique. RESULTS: : The luciferase-Tg rats ubiquitously expressed the marker
      gene. Conventional skin grafting apparently showed the long-term acceptance of
      luciferase-Tg rat skin on wild-type rats (>100 days), compared with grafting of
      GFP-Tg-derived skin (<10 days). This suggests less cellular immune responsiveness
      against the luciferase protein than GFP. Strikingly, organ transplants with heart
      and small bowel, and bone marrow cell transplantation showed viability and graft
      acceptance, demonstrating that cells and organs from luciferase-Tg rats are
      transplantable and their fate can be tracked for a sufficient time. Taking
      advantage of less immunogenic luciferase, cellular fate of transplanted mature
      hepatocytes was also examined. Transplanted hepatocytes proliferated and were
      monitored selectively in damaged liver, but not in healthy liver, for over 60
      days. CONCLUSIONS: We propose on the basis of these findings that the luciferase
      Tg rat system with modern optical imaging offers a new platform for a better
      understanding of stem cell biology and transplantation.

PMID- 16641606
TI  - A novel method of monitoring response to islet transplantation: bioluminescent
      imaging of an NF-kB transgenic mouse model.
AB  - BACKGROUND: Transplantation of encapsulated pancreatic islets is a novel
      therapeutic approach for the treatment of Type 1 diabetes mellitus that has the
      potential to circumvent both a limited islet supply and immunosuppression.
      Current methods for scoring the biocompatibility of the alginate-based capsules
      that sequester Islets of Langerhans include fabrication and implantation into the
      peritoneal cavity of mice, incubation, retrieval via peritoneal lavage, and
      observation of the number of cells or cell layers surrounding the capsules. This
      method allows only one data point to be obtained per animal. We describe a method
      to measure biocompatibility real time and in situ. This method of monitoring
      immune response using bioluminescent technology and a nuclear factor-kappa beta
      (NF-kB) sensitive transgenic mouse model allows many data points to be acquired
      per animal, reduces the number of animals required to obtain statistically
      significant immune response data over time, and in turn reduces error associated
      with animal variability. NF-kB is a transcription factor that coordinates the
      inflammatory and wound healing cascades by initiating the transcription of
      cytokines, chemokines, adhesion molecules, and proinflammatory genes. METHODS:
      Inflammation after the transplantation of five types of capsules was monitored
      for 6 six weeks after transplantation into the dorsal-cervical fat pad. RESULTS:
      Bioluminescence over 6-week time period: Capsule group 1.0+/-.00 normalized
      units, Bead group 1.3+/-.26 normalized units, No coat group .96+/-.48 normalized
      units, Sham group .96+/-.00 normalized units, Control group .17+/-.11 normalized
      units. CONCLUSIONS: This imaging modality was able to detect statistically
      significant differences in NF-kB activity between pre- and postoperative data
      points per mouse. It was also able to discern an unexpected increase in NF-kB
      activity due to capsule size instead of capsule wall composition over a 6-week
      time period.

PMID- 16641607
TI  - Comparison of calcitonin versus calcitonin + resistance exercise as prophylaxis
      for osteoporosis in heart transplant recipients.
AB  - BACKGROUND: Rapid bone loss occurs early after heart transplantation. There is no
      standard therapeutic intervention to prevent osteoporosis in heart transplant
      recipients (HTR). The purpose of this study was to determine the effectiveness of
      a regimen combining the antiresorptive properties of nasal calcitonin with the
      osteogenic stimulus of resistance exercise. METHODS: Eighteen candidates for
      heart transplantation were randomly assigned either to a group that received
      calcitonin and participated in 6 months of resistance exercise (n=10) or to a
      group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for 8
      months) was initiated 48 hr after transplantation. Resistance exercise was
      initiated 2 months after transplantation. Bone mineral density (BMD) of the total
      body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at 2 and 8
      months after transplantation. RESULTS: Total body and femur neck BMD did not
      decrease (P>or=0.05) below pretransplantation values at 2 months after
      transplantation in either group. BMD of the lumbar spine was significantly
      (P<or=0.05) and comparably decreased at 2 months after transplantation in the
      calcitonin (-10.1+/-1.8%) and calcitonin + training groups (-12.9+/-2.7%). At 8
      months after transplantation lumbar BMD was -16.9% below pretransplant values in
      the calcitonin group. In contrast, lumbar BMD was restored to within 5% of
      pretransplant levels in the calcitonin + training group. CONCLUSIONS: Calcitonin
      attenuates BMD loss in the total body and femur neck but not in trabecular bone
      of the lumbar vertebra. Mechanical loading, through progressive resistance
      exercise, is an osteogenic stimulus in HTR.

PMID- 16641608
TI  - Expression of MHC class I-related Chain B (MICB) molecules on renal transplant
      biopsies.
AB  - BACKGROUND: MICA and MICB (MHC class I-related chain A and B) are polymorphic
      genes that encode molecules related to MHC class I and are expressed on
      epithelial cells in response to stress. Incompatible donor MIC antigens can
      stimulate antibody production in transplant recipients. This study was designed
      to determine MICB expression in kidney pretransplant and any subsequent changes
      in expression following transplantation and to correlate changes with
      inflammatory markers and clinical events. METHODS: Paired renal biopsies obtained
      from living donor (n=10) and cadaveric allografts (n=50) before and 7 days
      posttransplant were stained for MICB, leukocytic infiltration, and HLA class II
      antigens. RESULTS: Variable tubular MICB expression was evident in donor biopsies
      [high 6/60 (10%), low/negative 13/60 (22%), intermediate 41/60 (68%)]. Following
      transplantation, MICB was up-regulated on renal tubules of 17/60 (28%) biopsies
      and was associated with MHC class II antigen induction (P=0.02) and leukocyte
      infiltration (P=0.01). Acute tubular necrosis leading to delayed graft function
      (DGF) and acute rejection (AR) cause cellular stress within the transplanted
      kidney. We found a strong association between up-regulation of MICB and cellular
      stress, 15/17 biopsies with up-regulated MICB expression had AR and/or DGF
      (P=0.003). CONCLUSIONS: This is the first study demonstrating variable levels of
      MICB expression in kidneys before transplantation and induction of MICB
      expression following renal transplantation. MICB expression is associated with
      HLA class II antigen induction, leukocytic infiltration of the graft and cellular
      stress in the transplanted kidney. Expression of MICB could contribute
      significantly to the alloimmune response in mismatched donors and recipients.

PMID- 16641609
TI  - Activation of human microvascular endothelial cells with TNF-alpha and
      hypoxia/reoxygenation enhances NK-cell adhesion, but not NK-Cytotoxicity.
AB  - BACKGROUND: Ischemia/reperfusion injury (I/R) and cellular rejection in solid
      organ transplantation are characterized by adhesion molecule up-regulation on the
      graft endothelium, a prerequisite for leukocyte recruitment. The contribution of
      NK cells to I/R and allograft rejection is not well understood. The aim of the
      present study was to investigate allogeneic interactions between human NK cells
      and microvascular endothelial cells (MVEC) with special regard to the
      differential impact of TNF-alpha and hypoxia/reoxygenation in an in vitro model
      of I/R. METHODS: MVEC were stimulated in vitro for 8 h with TNF-alpha, exposed to
      hypoxia (1% O2), hypoxia/reoxygenation, and combinations thereof in a hypoxia
      chamber. Cell surface expression of adhesion molecules on MVEC was analyzed by
      flow cytometry, and adhesion molecule shedding by ELISA. NK cell adhesion on MVEC
      was determined under shear stress, and NK cytotoxicity using Cr-release assays.
      RESULTS: Surface expression of ICAM-1, VCAM-1, and E-/P-selectin on MVEC was up
      regulated by TNF-alpha but unaffected by hypoxia/reoxygenation in the absence of
      TNF-alpha. ICAM-1 expression was further increased by a combination of TNF-alpha
      and hypoxia/reoxygenation, whereas TNF-alpha-induced E-/P-selectin expression was
      strongly reversed by hypoxia/reoxygenation. NK cell adhesion increased after
      exposing MVEC to TNF-alpha and hypoxia/reoxygenation. Susceptibility of MVEC to
      NK cytotoxicity was enhanced by TNF-alpha and slighty reduced by
      hypoxia/reoxygenation. CONCLUSIONS: Endothelial activation with TNF-alpha, but
      not hypoxia/reoxygenation, induced NK cytotoxicity whereas the combination
      thereof induced the strongest NK cell adhesion. Our findings suggesting a role
      for NK cells in allograft responses support the development of anti-inflammatory
      treatment strategies to prevent I/R.

PMID- 16641610
TI  - No evidence of association between NOD2/CARD15 gene polymorphism and
      atherosclerotic events after renal transplantation.
AB  - Stable renal transplant recipients (RTR) display high rates of atherosclerotic
      events (AE). Innate immunity and especially vascular inflammation play a role in
      the pathogenesis of atherosclerosis. It is illustrated both by an increased
      occurrence of postrenal transplant cardiovascular events in patients with
      elevated levels of C-reactive protein and by a correlation between posttransplant
      AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the
      influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro
      inflammatory activity and macrophage is present in early atherosclerotic lesions.
      The incidence of single nucleotide polymorphism (SNP) in the three major
      polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR
      and the correlation between such polymorphism and the development of AE was
      analyzed. No correlation was observed between NOD2 gene polymorphism and the
      occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does
      not appear to influence cardiovascular complications in RTR.

PMID- 16641611
TI  - Identification of patients at risk of acute rejection by pretransplantation and
      posttransplantation monitoring of soluble CD30 levels in kidney transplantation.
AB  - In this study, we investigated the impact of pre- and posttransplantation sCD30
      monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect
      of different immunosuppressive regimens on posttransplantation sCD30 levels in
      kidney recipients. Fifty patients receiving kidney allograft and 10 healthy
      donors were included in this retrospective cohort study. Eight patients developed
      biopsy-proven AR (19%). In pretransplantation samples, patients showed a
      significantly higher sCD30 than healthy controls. The pretransplantation and
      posttransplantation (day-15) sCD30 levels were significantly elevated in
      rejecting patients compared to non-rejecting patients. No significant differences
      among immunosuppressive regimens were found in posttransplantation sCD30 levels.
      High pretransplantation and posttransplantation (day 15) sCD30 levels are
      associated with increased risk of early AR, and sCD30 can be another tool to
      evaluate immunological risk prior to kidney transplantation. There was no
      difference in immunosuppressive regimens used in this study on
      posttransplantation sCD30 levels at the first month.

PMID- 16641612
TI  - Feasibility and safety of pancreatic islet transplantation in the liver by portal
      vein catheterization using the transjugular route.

PMID- 16641613
TI  - Proposed live donor nephrectomy complication classification scheme.

PMID- 16641614
TI  - Combined kidney-pancreas transplant: early abdominal catastrophe in the donor may
      not be a contraindication.

PMID- 16641615
TI  - Treatment of acute hypertension in patients with intracerebral hemorrhage using
      American Heart Association guidelines.
AB  - OBJECTIVE: To determine the feasibility and safety of treatment of acute
      hypertension in patients with intracerebral hemorrhage within 24 hrs of symptom
      onset. Elevated blood pressure, observed in up to 56% of patients with
      intracerebral hemorrhage, may predispose to hematoma expansion; on the other
      hand, reduction of blood pressure may reduce hematoma expansion and subsequent
      death and disability. DESIGN: Single-center prospective registry supplemented by
      retrospective chart review. SETTINGS: University-affiliated medical center with
      dedicated stroke service. PATIENTS: All patients admitted to the stroke service
      with spontaneous intracerebral hemorrhage and acute hypertension within 24 hrs of
      symptom onset. INTERVENTION: Patients were treated with intravenous nicardipine
      within 24 hrs of symptom onset to reduce and maintain mean arterial pressure of
      <130 mm Hg. The mean arterial pressure goal was consistent with the American
      Heart Association guidelines. MEASUREMENTS AND MAIN RESULTS: The primary outcome
      was the tolerability of the treatment as assessed by achieving and maintaining
      the mean arterial pressure goals for 24 hrs after initiation of intravenous
      nicardipine infusion. Other end points ascertained were: neurologic deterioration
      defined by a decline in Glasgow Coma Scale from pretreatment assessment by >or=2
      points or increase in National Institutes of Health Stroke Scale score by >or=2
      points and hemorrhage growth defined as an increase in the volume of
      intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-hr
      computed tomographic scan compared with the baseline computed tomographic scan.
      Rates of favorable outcome and death were ascertained at 1 month. Of the total 46
      patients admitted with intracerebral hemorrhage in our service, 29 patients were
      treated. Mean age of the treated patients was 58 +/- 13 yrs; ten were women.
      Initial National Institutes of Health Stroke Scale ranged from 1 to 38. The
      primary outcome of tolerability was achieved in 25 of the 29 patients (86%).
      Neurologic deterioration was observed in 4 of 29 patients. Hematoma enlargement
      was observed in five patients. Favorable outcome (defined as modified Rankin
      scale of <or=2) and death at 1-month was observed in 11 (38%) and 9 (31%) of the
      29 patients, respectively. CONCLUSIONS: We observed a high rate of tolerability
      among patients with intracerebral hemorrhage who were treated with intravenous
      nicardipine using mean arterial pressure goals defined by American Heart
      Association guidelines within 24 hrs of symptom onset.

PMID- 16641616
TI  - Dalteparin, a low molecular weight heparin, attenuates inflammatory responses and
      reduces ischemia-reperfusion-induced liver injury in rats.
AB  - OBJECTIVE: To examine whether dalteparin, a low molecular weight heparin,
      prevents hepatic damage by inhibiting leukocyte activation, we analyzed its
      effect on ischemia/reperfusion (I/R) injury of rat liver in which activated
      leukocytes play a critical role. DESIGN: Prospective, randomized, controlled
      study. SETTING: Research laboratory at a university medical center. SUBJECTS:
      Male Wistar rats weighing 220-280 g. INTERVENTIONS: Hepatic damage was evaluated
      by changes in serum transaminase concentrations after I/R. Coagulation
      abnormalities were evaluated by changes in serum concentrations of fragment E of
      fibrin and fibrinogen degradation products after I/R. Hepatic tissue blood flow
      was measured by laser-Doppler flow meter. Hepatic edema was evaluated by
      determination of the change in the wet/dry tissue weight ratio. Rats were
      intravenously injected with dalteparin or unfractionated heparin (300 units/kg)
      and subcutaneously injected with DX9056a, a selective inhibitor of activated
      factor X (3 mg/kg). To determine whether dalteparin inhibits leukocyte
      activation, we examined the effect of dalteparin on hepatic concentrations of
      interleukin-12, tumor necrosis factor-alpha, and hepatic myeloperoxidase activity
      after I/R in vivo. In addition, we examined increases in tumor necrosis factor
      alpha production in rat monocytes and in intracellular calcium concentrations in
      neutrophils in vitro. We also examined the effect of dalteparin on endothelial
      production of prostacyclin using isolated rat hepatic sinusoidal cells in vitro.
      MEASUREMENTS AND MAIN RESULTS: Intravenous administration of dalteparin inhibited
      increases in serum levels of both transaminases and serum concentrations of
      fragment E of fibrin and fibrinogen degradation products in animals subjected to
      hepatic I/R. Hepatic tissue blood flow after reperfusion was increased by
      dalteparin. Dalteparin inhibited hepatic edema, increases in hepatic tissue
      levels of interleukin-12 and tumor necrosis factor-alpha, and accumulation of
      neutrophils in animals subjected to hepatic I/R. Neither DX9065a nor
      unfractionated heparin showed any therapeutic effects, despite potent inhibition
      of increases in serum levels of fragment E of fibrin and fibrinogen degradation
      products. Neither monocytic tumor necrosis factor-alpha production nor neutrophil
      activation was inhibited by dalteparin in vitro. Dalteparin enhanced the hepatic
      I/R-induced increases in hepatic tissue levels of 6-keto-prostaglandin (PG)
      F1alpha, a stable metabolite of prostacyclin, which is capable of inhibiting
      monocytic tumor necrosis factor-alpha production. Pretreatment with indomethacin
      completely reversed both of the therapeutic effects of dalteparin, whereas
      pretreatment with NS-398, a selective inhibitor of cyclooxygenase-2, did not.
      Dalteparin did not directly increase the endothelial production of prostacyclin
      in vitro. CONCLUSION: Dalteparin might reduce I/R-induced liver injury in rats by
      attenuating inflammatory responses. These therapeutic effects might be
      independent of its anticoagulant activity but dependent on its capacity to
      enhance endothelial production of prostacyclin via cyclooxygenase-1 activation.
      Furthermore, the mechanism or mechanisms by which dalteparin promotes the
      endothelial production of prostacyclin in vivo might involve unknown factors
      other than endothelial cells.

PMID- 16641617
TI  - Paternal age and delivery before 32 weeks.
AB  - BACKGROUND: Advanced paternal age has been linked to early preterm delivery
      (before 32 weeks). METHODS: We analyzed live births from white, non-Hispanic
      primiparas recorded in U.S. birth certificates from 1995 to 2000 (excluding
      California). We examined 2,509,012 pregnancies of married women 20 to 34 years
      old, excluding unmarried women due to the high fraction of missing data on
      father's age. We defined the outcome according to the clinical estimate of
      gestation after excluding unlikely birth weights, because the estimate based on
      last menstrual period is particularly prone to errors at early gestations.
      RESULTS: Older paternal age was not associated with increased risk of early
      preterm delivery. The highest estimated odds ratio among fathers 50 years or
      older was 1.3 (95% confidence interval = 0.6-2.8) among women 20 to 24 years old.
      CONCLUSIONS: These U.S. data do not support an association between advanced
      paternal age and delivery before 32 weeks.

PMID- 16641618
TI  - Reliability and validity of 2 single-item measures of psychosocial stress.
AB  - BACKGROUND: Practical limitations in epidemiologic research may necessitate use
      of only a few questions for assessing the complex phenomenon called "stress." The
      objective of this study was to evaluate the measurement characteristics of 2
      single-item measures on the amount of stress and the ability to handle stress.
      METHODS: We selected 218 adults age 50 to 76 years living in western Washington
      state from a large prospective cohort study of lifestyle factors and cancer risk
      to evaluate the 3-month test-retest reliability and intermethod reliability of
      the stress questions. To assess the latter, we compared 2 single-item measures on
      stress with 3 more fully validated multi-item instruments on perceived stress,
      daily hassles, and life events, which assessed the same underlying constructs as
      the single-item measures. RESULTS: The test-retest reliabilities for the single
      item stress measures were good (kappa and intraclass correlations between 0.66
      and 0.74). The intermethod reliabilities comparing the 2 single-item stress
      measures with 3 multi-item instruments were moderate (r = 0.31-0.46) and
      comparable to correlations observed among the 3 multi-item instruments (r = 0.25
      0.47). CONCLUSIONS: The 2 single-item stress measures are reliable at measuring
      stress with validity similar to longer questionnaires. Single-item measures offer
      a practical instrument for assessing stress in large prospective epidemiologic
      studies that lack space for longer instruments.

PMID- 16641619
TI  - Founder's Lecture in plastic surgery.

PMID- 16641620
TI  - Microsurgery and hand surgery: early days, late nights: some reminiscences.

PMID- 16641621
TI  - Postbariatric surgery breast reshaping: the spiral flap.
AB  - INTRODUCTION: After massive weight loss, the breasts have poor shape, projection,
      and skin elasticity. Breast reshaping is recognized as difficult and may require
      excess nearby tissues. As the senior author's approach evolved over the past 4
      years, breast reshaping with the spiral flap became integral to an upper body
      lift. MATERIALS AND METHODS: After the weight loss has stabilized, body
      contouring surgery has been performed on 53 patients over a 3-year period. Six
      patients had mastopexy and/or augmentation only. Eighteen patients had spiral
      flap breast reshaping as part of an upper body lift. This lift is a reverse
      abdominoplasty that ends along the inframammary fold incision of the Wise pattern
      mastopexy and continues laterally to along the back roll. Excess tissue from the
      epigastrium and lateral back roll is deepithelialized and used for augmentation.
      These flap extensions of the central breast pedicle are spiraled around the
      breast for augmentation, shaping, and suspension. When more tissue is needed,
      saline-filled silicone implants have been used, preferably during a second stage.
      RESULTS: Follow up of this initial group ranged from 4 to 28 months with a mean
      of 11 months. In this initial effort, 14 of the 18 were pleased. In 3 patients,
      subsequent bilateral saline implants further augmented the breasts. Tip fat
      necrosis was evident by firmness of the tissues in 3 patients and resolved in all
      but 1. That 1 patient had operative debridement of the distal 50% of the flaps
      followed by saline-filled silicone implants. One patient was disappointed with
      the back scar. Two patients dislike the shape and fill of their breast and have
      not returned for revision. CONCLUSION: During 3 years of focused clinical
      activity, we have evolved the spiral flap reshaping with upper body lift into a
      comprehensive, effective, satisfying, and safe esthetic contouring of the breast
      and upper torso after massive weight loss performed with an upper body lift.

PMID- 16641622
TI  - Improving outcomes in bilateral breast reconstruction using autogenous tissue.
AB  - Bilateral breast reconstruction utilizing autologous free tissue transfer is a
      complex procedure with multiple options for donor tissue available. This study
      set out to compare the outcomes of patients undergoing bilateral breast
      reconstruction with muscle-sparing free TRAM flaps versus those undergoing
      bilateral reconstructions utilizing procedures which aim to minimize abdominal
      donor site morbidity in the form of deep inferior epigastric perforator (DIEP) or
      superficial inferior epigastric (SIEA) flaps. A retrospective review identified
      31 patients and 62 free flaps for bilateral autologous breast reconstruction at
      our teaching institutions in Rochester, NY. Patients receiving procedures which
      aimed to minimize donor-site morbidity experienced a shorter length of hospital
      stay versus those patients undergoing bilateral free TRAM procedures (P = 0.0494
      by t test and P = 0.0389 by parametric test). There was no significant difference
      in complication rates between these 2 groups. Other demographic and premorbid
      factors showed no difference between groups. Here, we demonstrate that bilateral
      autologous breast reconstruction with flaps which minimize donor site morbidity
      are a safe and effective option for bilateral reconstruction. Furthermore,
      patients who received bilateral breast reconstruction with abdominal wall sparing
      techniques (DIEP or SIEA flaps) had a significantly shorter length of hospital
      stay, with no significant difference in complication rates when compared with
      patients undergoing bilateral free TRAM procedures.

PMID- 16641623
TI  - Risk factors and complications in free TRAM flap breast reconstruction.
AB  - METHODS: The authors retrospectively reviewed 500 free TRAM flaps performed
      between 1992 and 2003. This cohort was subdivided based on smoking history,
      obesity, preoperative chemotherapy, preoperative radiation therapy, peripheral
      vascular disease, chronic obstructive pulmonary disease (COPD), and hypertension,
      and compared surgical complication rates. Measured complications included fat
      necrosis, mastectomy flap necrosis, abdominal flap necrosis, partial TRAM flap
      loss, wound infection, hematoma, seroma, vessel thrombosis, and abdominal hernia.
      Chi2 analysis and Fisher exact test were performed to determine differences
      between groups, and linear regression models were used to predict the risk
      factors of surgical complications. RESULTS: Smokers were more likely to have a
      higher incidence of wound infection (P = 0.01), mastectomy flap necrosis (P =
      0.015), abdominal flap necrosis (P = 0.033), and fat necrosis (P = 0.01). Obese
      patients were more likely to have higher rates of mastectomy flap necrosis (P =
      0.01) and hematoma (P = 0.01). Patients with peripheral vascular disease were
      more likely to have a higher incidence of wound infection (P = 0.031), and
      patients with preoperative radiation therapy were more likely to have a higher
      incidence of seroma (P = 0.043). Logistic regression showed that smoking was
      found to be a risk factor for fat necrosis (P = 0.006), wound infection (P =
      0.002), mastectomy flap necrosis (P = 0.039), and abdominal flap necrosis (P =
      0.042). Obesity was a risk factor for mastectomy flap necrosis (P = 0.002).
      Peripheral vascular disease was a risk factor for wound infection (P = 0.032).
      CONCLUSION: Awareness of risk factors and associated complications will lead to
      modification and individualization of surgical techniques in an attempt to limit
      these complications and continually improve outcomes.

PMID- 16641624
TI  - Applicability of the nipple-areola complex-sparing mastectomy: a prediction model
      using mammography to estimate risk of nipple-areola complex involvement in breast
      cancer patients.
AB  - The purpose of this study was to develop a prediction model that can be used to
      identify breast cancer patients at lowest risk for neoplastic nipple-areola
      complex (NAC) involvement to offer total NAC-sparing mastectomy with immediate
      reconstruction. Medical records, pathology slides, and mammograms were reviewed
      for all breast cancer patients treated with total mastectomy at Rhode Island
      Hospital between 2000 and 2004. The distance between the nipple and the closest
      tumor margin was measured using mammography. NAC involvement was identified in
      42% of the 31 study patients. Mammographic distance, pathologic stage, and tumor
      size were identified as independent predictors of malignant NAC involvement by
      multivariate analysis (rho < 0.05). Based on these predictors, a linear
      discriminant score, the NAC Involvement Score (NACIS), was computed to
      distinguish between the presence and absence of NAC involvement. For individual
      patients, positive NACIS values (> or = -0.3665) were associated with NAC
      involvement with a sensitivity of 92%, specificity of 77%, and negative
      predictive value of 93%. These preliminary findings indicate that the NACIS
      formula may be a useful clinical tool for selecting low-risk patients for total
      NAC-sparing mastectomy with immediate reconstruction.

PMID- 16641625
TI  - Conversion Furlow palatoplasty: salvage of speech after straight-line
      palatoplasty and "incomplete intravelar veloplasty".
AB  - INTRODUCTION: The straight-line palatoplasty with intravelar veloplasty (IVVP) is
      one option for cleft palate repair. However, not all IVVPs are performed
      uniformly. Many IVVPs only address the medialmost portion of the levator muscle,
      an "incomplete IVVP," failing to completely dissect and adequately transpose the
      entire levator muscle, "complete IVVP." We believe that for optimal speech
      results, IVVPs should completely mobilize and posteriorly displace the levator.
      We propose that a conversion Furlow palatoplasty performed with a "complete IVVP"
      will correct postoperative velopharyngeal insufficiency (VPI) and alleviate the
      need for pharyngoplasty. METHODS: Nineteen patients with postoperative VPI,
      having had prior straight-line palatoplasty and reported "IVVP," underwent
      conversion Furlow palatoplasty. Those with a pre- and postoperative Pittsburgh
      Weighted Speech Scale (PWSS) value and no other history of palatal surgeries were
      included in this study. Statistical analysis was performed by using the Wilcoxon
      signed ranks test. RESULTS: Patients' median age was 5.5 years (range, 4-15
      years), with 13 males and 7 females. The median preoperative PWSS score was 11.00
      (range, 3-24.5), and the median postoperative was 1.00 (range, 0-5) (P < 0.001).
      All subcategories of the PWSS were also improved. Eight children had a
      preoperative fistula, and all were successfully corrected. At the time of
      conversion Furlow palatoplasty, all patients demonstrated no evidence of previous
      IVVP as the levator muscle was found to be scarred to the posterior edge of the
      hard palate. CONCLUSION: The conversion Furlow palatoplasty can be used to
      significantly improve VPI and salvage speech after a straight-line palatoplasty
      with an "incomplete IVVP." Patients with postoperative VPI should first be
      considered for conversion Furlow palatoplasty performed with a "complete IVVP"
      prior to progressing to pharyngoplasty.

PMID- 16641626
TI  - Diagnosis and treatment of velopharyngeal insufficiency: clinical utility of
      speech evaluation and videofluoroscopy.
AB  - INTRODUCTION: The workup of velopharyngeal insufficiency (VPI) includes speech
      pathology evaluation and examination of velopharyngeal anatomy and physiology.
      This study sought to determine whether perceptual speech symptoms were predictive
      of velopharyngeal closure. PATIENTS AND METHODS: A retrospective chart review of
      patients with VPI following primary palatoplasty was performed. All patients
      underwent perceptual speech evaluation using the Pittsburgh Weighted Speech Scale
      (PWSS) and examination of velopharyngeal anatomy by videofluoroscopy. PWSS scores
      were correlated to velopharyngeal closure. RESULTS: All patients exhibited
      clinical VPI (PWSS = 5-27). No patient demonstrated complete velopharyngeal
      closure on videofluoroscopy. Velopharyngeal closure on the lateral view showed a
      statistically significant, moderate correlation with both the PWSS total score
      (rs = -0.424; P = 0.03) and the phonation subscore (rs = -0.405; P = 0.04).
      CONCLUSIONS: Although certain aspects of speech are related to velopharyngeal
      anatomy, speech and videofluoroscopic studies each provide unique information in
      the workup of VPI. Selection of surgical approach often depends on anatomic
      factors, and improvement in speech postoperatively indicates successful
      treatment.

PMID- 16641627
TI  - Candidate genes for oral-facial clefts in Guatemalan families.
AB  - Nonsyndromic cleft lip +/- cleft palate (CL/P) is a complex trait of unknown
      etiology. Most genetic studies of CL/P define affection status in a way that
      ignores subtle subclinical manifestations, resulting in a potential loss of
      statistical power. This study investigated 10 candidate genes in 155 individuals
      from 25 Guatemalan CL/P families. High-resolution ultrasound images of the
      orbicularis oris (OO) muscle were obtained. CL/P was present in 28 family
      members; an additional 10 had subcutaneous OO muscle defects. Family-based
      association studies were performed for both narrow (CL/P only) and broad (CL/P
      plus OO muscle defects) definitions of affection status. PVRL1 was significantly
      associated under both definitions (P = 0.04, narrow; P = 0.02, broad).
      Association with JAG2 improved from P = 0.09 under the narrow definition to P =
      0.04 under the broad definition. Broadening the oral-facial cleft phenotype to
      include subclinical variants may improve power in genetic studies.

PMID- 16641628
TI  - A soft-tissue approach to midfacial hypoplasia associated with Treacher Collins
      syndrome.
AB  - INTRODUCTION: Treacher Collins syndrome is an autosomal dominant mandibulofacial
      dysostosis with characteristic hard- and soft-tissue facial abnormalities. These
      include ocular malformations, ear malformations, and hypoplasia of the facial
      skeleton, especially of the malar bones and mandible. Traditionally, surgical
      correction of the facial abnormalities has focused on skeletal reconstruction to
      restore facial form and symmetry. In this report, we describe the use of
      customized parascapular free flaps, after standard reconstructive surgeries, for
      the correction of defects of facial contour in Treacher Collins patients. In most
      cases, bony reconstruction of the zygoma or periorbita is not required. METHODS:
      From June 1995 to December 2003, 8 patients with Treacher Collins syndrome
      underwent microsurgical correction of facial contour using 16 free flaps. In all
      patients, staged parascapular free flaps were used for reconstruction. The
      microvascular technique involved a 2-team approach with simultaneous ipsilateral
      parascapular flap harvest and facial pocket dissection. The flaps were contoured,
      revascularized (14 superficial temporal vessels, 2 facial vessels), and inset. No
      vein grafts were used. The patients were followed for a minimum of 1 year, and
      postoperative evaluation included medical photography, visual assessment, and
      evaluation by the patient and family. RESULTS: Seven patients had previous facial
      skeleton correction using craniofacial techniques. The age at operation ranged
      from 4-19 years. Sixteen parascapular free flaps were used in the 8 patients.
      Postoperative complications were limited to 1 hematoma. There were no partial or
      total flap losses. All of the patients had improved facial contour and symmetry.
      Overlying skin tone and color similarly improved. CONCLUSION: After traditional
      skeletal reconstruction for the complex craniofacial defects of Treacher Collins
      syndrome, deficiencies in facial contour and symmetry usually persist. Customized
      soft-tissue free flaps can be employed to differentially resurface these defects
      and achieve optimal esthetic results in these challenging patients.

PMID- 16641629
TI  - Reconstruction of extensive partial or total sacrectomy defects with a
      transabdominal vertical rectus abdominis myocutaneous flap.
AB  - Following partial or total sacrectomy, extensive soft tissue defects are
      frequently created. These ablations typically involve an anterior and a posterior
      approach, creating a large communication between the abdominal cavity and the
      central gluteal region. Local flap options are usually not sufficient for
      definitive closure of these large defects. We have found that the most useful
      option for reconstruction in these cases is a vertical rectus abdominis
      myocutaneous (VRAM) flap, passed transabdominally through the peritoneal cavity
      into the sacral defect during the initial anterior-approach portion of the
      procedure and then inset following completion of the posterior-approach final
      resection. Advantages of the VRAM flap are that it can supply ample skin, as well
      as soft tissue bulk, is easy to perform, and does not require microvascular
      techniques. Utilizing a prospectively maintained database, all patients over the
      last 14 years who underwent reconstruction utilizing a transabdominal VRAM flap
      following extensive partial or total sacrectomy with intraabdominal communication
      were identified. A retrospective chart review was then performed. Our study
      population consisted of 12 patients with a mean age of 58.5 years. Following
      sacrectomy, all patients underwent reconstruction with a VRAM flap. Flap sizes
      averaged 9.1 x 27 cm. Early flap complications included 3 small areas of flap
      necrosis at the distal, superior portion of the flap, 2 of which required minimal
      operative intervention of debridement and reclosure. No late flap complications
      have occurred, and all 12 patients completely healed, with a mean follow-up time
      of 29.1 months. Following sacrectomy, extensive soft tissue defects are created
      in the sacral area and communicate with the abdominal cavity. In these
      situations, we have found the inferiorly-based pedicled VRAM, passed
      transabdominally, to be the most reliable and useful choice of flap
      reconstruction. It has a low incidence of complications, low morbidity, and is
      easy to perform with a high success rate.

PMID- 16641630
TI  - Limb salvage of infected knee reconstructions for cancer with staged revision and
      free tissue transfer.
AB  - Periprosthetic infections of oncologic reconstructions have an amputation rate
      between 37% and 87%. Eleven patients with an infected knee reconstruction
      following limb salvage surgery for cancer were treated with the staged protocol.
      All patients underwent prosthetic removal and implantation of an antibiotic
      impregnated cement spacer, i.v. antibiotic therapy, repeat debridement and spacer
      change, and delayed prosthetic reconstruction and free tissue transfer. At the
      time of reconstruction, the median bone defect was 185 mm. The mean soft tissue
      defect was 112 cm2. Coverage was obtained with a free musculocutaneous flap. All
      limbs were spared without amputation or flap loss. The mean functional outcome as
      measured by the Musculoskeletal Tumor Society lower extremity score was 23 of 30.
      Infections of large prosthetic reconstructions about the knee can be salvaged
      successfully with repetitive debridement, staged prosthetic reimplantation, and
      free tissue transfer. Free tissue transfer improves the soft tissue envelope and
      allows restoration of joint motion. LEVEL OF EVIDENCE: Case Series. Level IV.

PMID- 16641631
TI  - Use of the anterolateral thigh flap as an alternative to the rectus flap in obese
      and overweight patients.
AB  - INTRODUCTION: Oncologic reconstruction in obese patients can be challenging.
      Donor tissues, such as the rectus flap, can be excessively bulky and result in
      significant cosmetic and functional deformities. Although the use of the
      anterolateral thigh (ALT) flap as an alternative to the radial forearm flap has
      been extensively described, few studies have evaluated the use of the ALT flap as
      an alternative to the rectus flap. The purpose of this study was to evaluate our
      experience with the ALT flap in overweight or obese patients. METHODS: A
      retrospective review was conducted of all ALT flaps performed over a 2-year
      period at Memorial Sloan-Kettering Cancer Center. All patients with a body mass
      index (BMI) >25 kg/m2 were identified and evaluated. RESULTS: Twenty-seven
      patients underwent ALT flap reconstruction during the study period. Of these, 11
      patients were overweight (BMI, 25.1-30 kg/m2) or obese (BMI, >30 kg/m2).
      Reconstructions were performed for a variety of oncologic defects, including head
      and neck (n = 7), extremity (n = 2), chest wall (n = 1), and abdominal wall (n =
      1). Complications were, in general, mild and infrequent. One patient experienced
      a minor infection, 1 patient had partial flap loss, and 2 patients had partial
      skin graft loss at the donor site. There were no flap losses. CONCLUSIONS: The
      ALT flap is a safe and reliable flap for reconstruction of diverse defects in
      overweight or obese patients. Large flaps can be designed and tailored to the
      defect by harvesting variable amounts of skin, subcutaneous tissues, fascia, and
      muscle. The ALT flap may be a good alternative to the rectus flap in overweight
      or obese patients.

PMID- 16641632
TI  - The propeller flap version of the adductor muscle perforator flap for coverage of
      ischial or trochanteric pressure sores.
AB  - Recidivism after flap coverage of ischial and trochanteric pressure sores is
      predictably common. Available local flap options are limited in number and must
      be cautiously preserved as long as possible for these patients who are destined
      to have a lifelong vulnerability for recurrence. Muscle perforator flaps have
      been introduced as another set of alternatives to solve this conundrum. Since the
      posteromedial thigh often has been previously unviolated by the usual workhorse
      flaps selected for this problem, the adductor perforator flap will then usually
      still be available as an important "backup" option. If designed as a propeller
      flap, this version after rotation will cover the defect and simultaneously allow
      direct donor-site closure to avoid the need for a skin graft.

PMID- 16641633
TI  - The osteogenic potential of adipose-derived stem cells for the repair of rabbit
      calvarial defects.
AB  - INTRODUCTION: Bone replacement is often necessary during reconstruction of
      craniofacial anomalies or trauma. Adipose-derived stem cells (ASCs) possess
      osteogenic potential and are a promising cell source for bone tissue engineering.
      The present study was designed to assess the osteogenic potential and utility of
      using ASCs to regenerate bone in a rabbit calvarial defect model. METHODS: Rabbit
      ASCs were seeded on gelatin foam (GF) scaffolds and induced in osteogenic medium
      containing bone morphogenetic protein (BMP)-2. Thirty-four 8-mm calvarial defects
      were randomly treated with autograft, no treatment, GF scaffold, GF + ASCs, or GF
      + osteoinduced ASCs. After 6 weeks, calvaria were harvested and underwent
      histologic and radiologic analyses to compare healing between the treatment
      groups. RESULTS: Defects treated with autograft underwent complete healing.
      Radiologically, there were no significant (P > 0.05) differences in healing among
      empty defects, and those treated with GF alone or GF plus osteoinduced ASCs.
      Osteoinduced ASCs exhibited significantly (P < 0.05) greater healing than
      noninduced ASCs. CONCLUSION: Preimplantation osteoinduction of ASCs enhances
      their osteogenic capacity. Lack of a significant osteogenic effect of ASCs on
      calvarial healing at 6 weeks may be secondary to use of noncritical-sized
      defects. Larger defects would likely demonstrate the osteogenic potential of ASCs
      more definitively.

PMID- 16641634
TI  - Surgical treatment of Treacher Collins syndrome.
AB  - Morphology, genetic conditioning, terminology, and the principles of treatment of
      Treacher Collins syndrome have been presented on the basis of our own material,
      as well as review of literature. Fifty patients (27 males, 23 females) were
      operated on at the Hospital of Plastic Surgery in Polanica Zdroj from 1976 to
      2005. The patients were first seen when they were from 1 to 32 years of age
      (mean, 7). The disease was hereditary in 17 patients, while the remaining
      subjects did not reveal any genetic conditioning. The lifesaving surgical
      treatment was undertaken in 4 children with the most severe form of the disease
      who presented with dyspnea and paroxysmal apnea. In those cases, the treatment
      aimed at improving the respiratory function by restoring patency of the nostrils
      and distraction of the mandible. Twelve patients were operated on for cleft
      palate between 1 and 2 years of age. Twelve patients had eyelid correction with
      the use of musculocutaneous flap transposition from the upper eyelid (Z-plasty).
      The zygomatic bone and lateral wall of the orbit were reconstructed by means of
      iliac bone grafts in 26 patients. The auricular reconstruction was usually
      undertaken after 10 years of age. Nine patients underwent bilateral auricular
      reconstruction by means of a modified Brent method. Fifteen patients aged 12-14
      had chin osteotomy according to the Obwegeser method. Nasal osteotomy was
      performed in 10 patients with characteristic broad, long, and hooked noses, who
      were operated on after 16 years of age and after completion of orthognathic
      treatment. In total, 258 surgical procedures were performed in 50 patients, an
      average of 5.2 operations per every patient. Apart from a multistage surgical
      treatment, the patients required a combined multidisciplinary approach, mainly
      due to hearing impairment and occlusal disturbances. The obtained outcome of
      treatment, although far from being perfect, but still beneficial, confirmed the
      correctness of applied approach but at the same time pointed to the necessity of
      introducing new methods of treatment aiming, among others, at compensating for
      the tissue deficiency by means of tissue engineering.

PMID- 16641635
TI  - Invited discussion: Surgical treatment of Treacher Collins syndrome.

PMID- 16641636
TI  - Complications in a consecutive series of 250 free flap operations.
AB  - The purpose of this study was to determine the rate of major and minor flap,
      donor site, and systemic complications in a consecutive series of 250 free flap
      operations. The following factors were analyzed to determine their significance
      on complication rates: age of patient, gender, wound etiology, smoking history,
      type of flap, operative time, vein graft use, surgeon experience, and the
      presence of comorbid disease. The major flap, donor-site, and systemic
      complication rates were 17.2%, 2%, and 6.4%, respectively. The minor flap, donor
      site, and systemic complication rates were 7.2%, 12.8%, and 7.2%, respectively.
      The presence of comorbid medical condition was the only factor which had a
      statistically significant impact on the rate of major flap complications (P =
      0.02). Age and comorbid disease impacted on major systemic complications (P =
      0.04).

PMID- 16641637
TI  - Bilobed fasciocutaneous flap closure of large meningomyeloceles.
AB  - BACKGROUND: Closure of large meningomyelocele defects presents a challenging
      problem. In this paper, the procedure and outcome of bilobed fasciocutaneous flap
      closure of large meningomyeloceles have been discussed. MATERIALS AND METHODS:
      Bilobed fasciocutaneous flap was used in 20 patients with large meningomyelocele
      defects, the largest of which was 77 cm2. A fasciocutaneous dissection was
      performed and the defect area was covered by tension-free closure. RESULTS: In
      the follow-up period of 6 weeks, partial flap loss in a patient and cerebrospinal
      fluid leak inferior to the flap in another 2 were observed. These patients
      recovered by dressing without flap loss. CONCLUSIONS: Utilization of bilobed
      flaps for closure of large meningomyelocele defects seems to be an effective and
      reliable procedure, with advantages of decreased operative time, minimal
      bleeding, the suture lines for dura and flap not superimposed, and low morbidity.

PMID- 16641638
TI  - Total face reconstruction using a pre-expanded, bilateral, extended, parascapular
      free flap.
AB  - A 37-year-old male sustained extensive, self-inflicted gasoline burns to his
      head, face, chest, upper extremities, and anterior thighs. Although he underwent
      initial resuscitation and skin grafting at a regional burn center, he presented
      to our clinic with thick, unstable burn scars covering his face and scalp. He had
      multiple functional and esthetic needs that are described. He required
      approximately 30 x 35 cm of skin to resurface his entire face and anterior scalp.
      His back and buttocks were his only unscarred, potential donor sites. Authors
      have described use of a bilateral parascapular free flap for similar deformities.
      This patient required pre-expansion of this free flap to maximize available
      tissue and minimize the donor defect. This technique provided this patient with a
      large area of healthy skin and soft tissue that will ultimately provide this
      patient with an improved functional and esthetic result.

PMID- 16641639
TI  - Optimal parameters for marking upper blepharoplasty incisions: a 10-year
      experience.
AB  - Although a variety of techniques for upper blepharoplasty have been described,
      few studies illustrate and clinically evaluate a system for marking incisions.
      Presented is a 10-year experience using a specific method for marking upper
      blepharoplasty incisions that consistently yielded excellent esthetic results.
      All upper blepharoplasties performed by the senior author between April, 1994 and
      April, 2004 were reviewed. Markings were designed to end the medial incision 6 mm
      from the angular vein, end the lateral incision 12 mm from the palpebral fissure,
      and to extend the incisions superiorly at 45 degrees. Over 10 years, 476 patients
      underwent cosmetic upper blepharoplasty. There were 22 (4.6%) revisions. Eighteen
      (3.8%) were performed in clinic using CO2 laser, and 4 (0.8%) patients required
      surgical revision. Patient satisfaction was high, and no scars were visible
      outside the brow. Excellent outcomes can be expected using this simple,
      reproducible, and widely applicable system for marking upper blepharoplasty
      incisions.

PMID- 16641640
TI  - The breast implant story.

PMID- 16641641
TI  - Vascular anatomy of the lateral pterygoid muscle.

PMID- 16641642
TI  - Spongostan used as a carrier for diced cartilages in rhinoplasties.

PMID- 16641643
TI  - Postobese patients and inherent surgical complications.

PMID- 16641645
TI  - Toward a zero VAP rate: personal and team approaches in the ICU.
AB  - In a fast-paced setting like the intensive care unit (ICU), nurses must have
      appropriate tools and resources in order to implement appropriate and timely
      interventions. Ventilator-associated pneumonia (VAP) is a costly and potentially
      fatal outcome for ICU patients that requires timely interventions. Even with
      established guidelines and care protocols, nurses do not always incorporate best
      practice interventions into their daily plan of care. Despite the plethora of
      information and guidelines about how to apply interventions in order to save
      lives, managers of ICUs are challenged to involve the bedside nurse and other ICU
      team members to apply these bundles of interventions in a proactive, rather than
      reactive, manner in order to prevent complications of care. The purpose of this
      article is to illustrate the success of 2 different methods utilized to improve
      patient care in the ICU. The first method is a personal process improvement
      model, and the second method is a team approach model. Both methods were utilized
      in order to implement interventions in a timely and complete manner to prevent
      VAP and its related problem, hospital-associated pneumonia, in the ICU setting.
      Success with these 2 methods has spurred an interest in other patient care
      initiatives.

PMID- 16641647
TI  - Central venous access device infections in the critical care unit.
AB  - Central venous access devices are indispensable tools in caring for the gravely
      ill patients in today's critical care units. Unfortunately, they are also one of
      the major sources for nosocomial infections in the hospital setting. This article
      explores the pathophysiology and risk factors related to central venous access
      devices infections, and examine prevention strategies. The critical care nurse,
      using evidence-based practice guidelines in the care of these lines, can be
      instrumental in preventing catheter-related infections.

PMID- 16641648
TI  - Controlling blood glucose levels to reduce infection.
AB  - Achieving and maintaining tight glucose control in the critically ill patient is
      becoming the standard of care across the country. It is well established that
      hyperglycemia is common in critically ill patients, and recent studies have shown
      a possible connection between hyperglycemia and the ability to fight infection.
      Healthcare providers face many challenges when choosing to implement this
      evidence-based practice into their standard of patient care. The purpose of this
      article is to share one hospital's collaborative approach to tight glucose
      control.

PMID- 16641649
TI  - Leveraging your culture for change.
AB  - The focus of this article is on understanding how to assess the impact that
      culture has on the acceptance and implementation of new ideas. Some guidance is
      offered on how to develop a strategy for addressing a unit's local culture to
      minimize barriers to change and maximize the potential for successful
      implementation of best practices.

PMID- 16641650
TI  - A new role for the ACNP: the rapid response team leader.
AB  - The implementation of a rapid response team or medical emergency team is 1 of the
      6 initiatives of the Institute for Healthcare Improvement's 100,000 Lives
      Campaign with the goal to reduce the number of cardiopulmonary arrests outside
      the intensive care unit and inpatient mortality rates. The concept of RRT was
      pioneered in Australia and is now being implemented in many hospitals across the
      United States. This article reviews the current literature and describes the
      implementation of an RRT in a community hospital. The first-quarter data after
      implementation are described. The unique role of the acute care nurse
      practitioner in this hospital's model is described.

PMID- 16641651
TI  - Moral discord, cognitive coping strategies, and medical intensive care unit
      nurses: insights from a focus group study.
AB  - Moral discord occurs when contextual factors prevent nurses from implementing
      felt moral mandates. Medical intensive care unit (MICU) nurses frequently
      confront moral issues and hold themselves personally responsible for their moral
      actions. They use a variety of cognitive coping strategies to deal with moral
      discord. This article describes common moral dilemmas encountered by MICU nurses,
      explores patterns of both conscious and unconscious cognitive coping behaviors,
      and reviews steps that nurses can take to reduce the degree of moral discord they
      experience.

PMID- 16641652
TI  - Endothelin-1-mediated inflammation in acute renal failure.
AB  - Acute renal failure presents a serious and life-threatening problem in
      hospitalized patients. Current therapies address the systemic alterations in
      renal failure. Cellular changes also occur. These changes affect the glomerular
      filtration rate and the integrity of the glomerular membrane. ET-1, the most
      potent vasoconstrictor known, has a negative effect on both the rate of
      filtration and the integrity of the filtering membrane in renal failure. Using ET
      1 antagonists along with the current therapies may prove useful in patients.

PMID- 16641653
TI  - Getting started kit: prevent ventilator-associated pneumonia: how-to guide.

PMID- 16641654
TI  - Low health literacy: a challenge to critical care.
AB  - Health literacy-"the degree to which individuals have the capacity to obtain,
      process, and understand basic health information and services needed to make
      appropriate health decisions"-has been identified as a cross-cutting quality-of
      care issue by the Institute of Medicine. This article defines the scope of the
      health literacy problem, discusses the literacy demands of critical care, and
      offers strategies for nurses to improve the quality of health communication with
      patients and families in the critical care environment.

PMID- 16641655
TI  - Grounding coverage in value: a paradigm for linking quality and costs.

PMID- 16641656
TI  - Racial differences in impact of coverage on diabetes self-monitoring in a health
      maintenance organization.
AB  - BACKGROUND: Insurance coverage of patient self-management devices like self
      monitoring blood glucose (SMBG) equipment may help to reduce race-related
      barriers to effective care. OBJECTIVES: We examined whether providing free home
      glucose monitors had greater impacts on self-monitoring among black versus white
      patients with diabetes. RESEARCH DESIGN: Using electronic medical record data
      (1992-1996), we used longitudinal survival analysis to examine racial differences
      in rates of initiation of SMBG after coverage and rates of discontinuation of
      SMBG 18 months after initiation. We used piecewise Cox models to compare relative
      rates of SMBG initiation between black and white patients before and after the
      policy. SUBJECTS: The study cohort included 2275 continuously enrolled adult
      patients with diabetes in a large, staff model HMO. Multivariate models were
      restricted to patients using oral therapy. RESULTS: Controlling for time
      dependent and fixed effects, black patients were as likely to initiate SMBG as
      white patients before the policy (hazard ratio 1.14; 95% confidence interval 0.86
      1.50) but more likely after the policy (hazard ratio 1.33; 95% confidence
      interval 1.01-1.76). Among postpolicy SMBG initiators, black patients were
      consistently at higher risk of SMBG discontinuation than white patients over time
      (P < 0.05). By the end of follow-up, discontinuation rates were 78% among black
      patients and 64% among white patients. CONCLUSIONS: The policy is effective in
      triggering additional diabetes patients to self-manage, particularly black
      patients. However, persistence after initiation of monitoring is short-lived.
      Although our results show the potential of such policies to narrow racial gaps in
      self-management among racial minority groups, further interventions may be needed
      to promote long-term adherence.

PMID- 16641657
TI  - Primary care patients' involvement in decision-making is associated with
      improvement in depression.
AB  - BACKGROUND: Depression is undertreated in primary care settings. Little research
      investigates the impact of patient involvement in decisions on guideline
      concordant treatment and depression outcomes. OBJECTIVE: The objective of this
      study was to determine whether patient involvement in decision-making is
      associated with guideline-concordant care and improvement in depression symptoms.
      DESIGN: Prospective cohort study. SETTING: Multisite, nationwide randomized
      clinical trial of quality improvement strategies for depression in primary care.
      SUBJECTS: Primary care patients with current symptoms and probable depressive
      disorder. MEASUREMENTS: Patients rated their involvement in decision-making (IDM)
      about their care on a 5-point scale from poor to excellent 6 months after entry
      into the study. Depressive symptoms were measured every 6 months for 2 years
      using a modified version of the Center for Epidemiologic Studies-Depression (CES
      D) scale. We examined probabilities (Pr) of receipt of guideline-concordant care
      and resolution of depression across IDM groups using multivariate logistic
      regression models controlling for patient and provider factors. RESULTS: For each
      1-point increase in IDM ratings, the probability of patients' report of receiving
      guideline-concordant care increased 4% to 5% (adjusted Pr 0.31 vs. 0.50 for the
      lowest and highest IDM ratings, respectively, P < 0.001). Similarly, for each 1
      point increase in IDM ratings, the probability of depression resolution increased
      2% to 3% (adjusted Pr 0.10 vs. 0.19 for the lowest and highest IDM ratings
      respectively, P = 0.004). CONCLUSIONS: Depressed patients with higher ratings of
      involvement in medical decisions have a higher probability of receiving guideline
      concordant care and improving their symptoms over an 18-month period.
      Interventions to increase patient involvement in decision-making may be an
      important means of improving care for and outcomes of depression.

PMID- 16641658
TI  - Elective percutaneous coronary intervention without on-site cardiac surgery:
      clinical and economic implications.
AB  - BACKGROUND: Low procedural complication rates, barriers to access, and patient
      preference have encouraged the development of percutaneous coronary intervention
      (PCI) programs at centers that are often closer to home but without on-site
      cardiac surgical capability. OBJECTIVES: We compared clinical and economic
      outcomes associated with performing low-risk elective PCI at a community hospital
      without on-site cardiac surgery with those obtained at a more remote tertiary
      care center with on-site cardiac surgery. DESIGN AND MEASURES: We matched 257
      patients undergoing low-risk, elective PCI at a community hospital (Immanuel St.
      Joseph's Hospital [ISJ] between January 27, 2000, and July 31, 2002) to 514 PCI
      patients treated at a tertiary care hospital (Saint Marys Hospital [SMH] between
      January 27, 2000, and April 30, 2002) based on clinical and lesion criteria.
      Clinical outcomes (in-hospital procedural success and target vessel failure
      during long-term follow up) and economic outcomes (direct medical costs, billed
      charges, and hospital length of stay [LOS]) were compared between groups. The
      Mayo Clinic PCI Registry (containing clinical, angiographic, and follow-up data)
      and administrative data were used in matching and outcomes assessment. RESULTS:
      Procedural success was achieved more often among ISJ-treated patients (99% vs.
      95%; P = 0.02); however, no difference in target vessel failure rates was
      observed during a median follow-up time of 3.1 years (estimated 1-year event
      rate: 15.2% vs. 14.8%; P = 0.46). ISJ-treated patients incurred, on average,
      $3024 more in estimated total costs ($13,771 vs. $10,746; P < 0.001) and $6084
      more in billed charges (P < 0.001), but incurred similar LOS post procedure (1.53
      days). CONCLUSIONS: Similar clinical outcomes were achieved at a community
      hospital without on-site cardiac surgery but at significantly increased direct
      medical cost. Patients, providers, hospitals, payers, and policymakers should
      consider whether the benefits associated with locally provided specialized
      cardiovascular services warrant this additional cost.

PMID- 16641659
TI  - Effect of dental practice characteristics on racial disparities in patient
      specific tooth loss.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that dental
      practice characteristics are associated with tooth loss incidence with both tooth
      specific and patient-specific characteristics already taken into account.
      RESEARCH DESIGN: A population-based prospective cohort study was conducted. In
      person interviews and clinical examinations were done at baseline, 24, and 48
      months, with telephone interviews every 6 months. Practices that coincidentally
      served participants in the study completed practice characteristics
      questionnaires. To increase inferential power when testing practice-level
      effects, detailed tooth-specific and patient-specific data were simultaneously
      taken into account in tests for association between practice-level effects and
      tooth loss. SETTING: Data were from the Florida Dental Care Study. The key health
      outcome was tooth loss, a leading measure of a population's oral health.
      PARTICIPANTS: Eight hundred seventy-three African-Americans and non-Hispanic
      whites who had at least 1 tooth. RESULTS: Certain practice characteristics were
      associated with tooth loss, including the racial mix of the practice's patient
      population; persons who attended practices with higher percentages of African
      Americans were more likely to receive a dental extraction regardless of the
      individual patient's race. CONCLUSIONS: This is the first longitudinal report of
      increased risk for tooth loss resulting from practice-level effects. Although a
      patient-level racial disparity remained evident, and even with detailed tooth
      specific and patient-level characteristics taken into account, racial differences
      in characteristics of practices attended independently contributed to the patient
      level racial disparity in health.

PMID- 16641660
TI  - The impact of physician attitudes and beliefs on treatment decisions: lipid
      therapy in high-risk patients.
AB  - BACKGROUND: Despite clinical guidelines, many patients with hypercholesterolemia
      do not achieve treatment goals in clinical practice. OBJECTIVES: This study
      examined physician attitudes and beliefs about hyperlipidemia and whether they
      are associated with lipid treatment decisions. METHODS: This was a cross
      sectional study of 107 physicians who completed a validated survey of attitudes
      and beliefs about hyperlipidemia and provided treatment histories for 1187 statin
      treated patients with coronary heart disease (CHD) or who were CHD risk
      equivalent. Logistic regressions (using generalized estimating equation)
      estimated the impact of patient characteristics and physician attitudes and
      beliefs on whether a patient received increases in the statin dose. RESULTS:
      Approximately 70% of the 843 patients who were not at low-density lipoprotein
      cholesterol goal (<100 mg/dL) with initial statin therapy received a dose
      increase, although only one-half attained goal. Controlling for patient
      characteristics, patients whose physicians believed "close enough to goal is good
      enough" had 47% lower odds of having a dose increase (odds ratio [OR], 0.53; 95%
      confidence interval [CI], 0.34-0.82), whereas patients whose physicians believed
      "statins are effective" had almost twice the odds of having a dose increase (OR,
      1.78; 95% CI, 1.05-3.00). CONCLUSIONS: Although the understanding of basic and
      clinical science remains fundamental, clinical guideline authors may want to
      consider the importance of physician attitudes and beliefs in determining
      translation of their guidelines into clinical practice.

PMID- 16641661
TI  - Differences in access to outpatient medical care for black and white adults in
      the rural South.
AB  - OBJECTIVES: We compared black and white adults in the rural South on multiple
      indicators of access to outpatient medical care and assessed whether any
      differences might be explained by group differences in socioeconomic situations
      or proximity to medical resources. DESIGN: Cross-sectional telephone survey.
      SUBJECTS: Survey respondents were 1237 black and 2158 white adults from 113 rural
      counties in 6 southern states. MEASURES: Blacks and whites were compared on a
      variety of commonly used survey measures of access, some followed in the Healthy
      People 2010 Initiative. Access comparisons were adjusted for age, gender, and
      health status and then reassessed with adjustments for individual socioeconomic
      indicators and county medical resources: physician-to-population ratios, the
      presence of hospitals and federally qualified health centers, and urban
      adjacency. RESULTS: Compared with whites, blacks reported similar or higher use
      of outpatient services over the previous year, including the likelihood of having
      had an outpatient physician visit and regular checkup. Nevertheless, blacks more
      often reported forgoing needed care, encountering various barriers, and
      experiencing dissatisfaction with some aspects of care. Adjusting for
      socioeconomic factors generally reduced but did not eliminate black-white access
      differences, whereas adjusting for county medical care resources did not affect
      measured group differences. CONCLUSIONS: Blacks and whites in the rural South
      report similar use rates of outpatient medical care, but blacks more often report
      unmet needs, barriers to care, and dissatisfaction with care. Beyond
      socioeconomic differences, black versus white differences in sites of care, the
      quality of care received, the quality of interactions with providers, and
      expectations for their care may explain group reported access differences.

PMID- 16641662
TI  - Racial/ethnic differences in diabetes care for older veterans: accounting for
      dual health system use changes conclusions.
AB  - BACKGROUND: Veterans Health Administration (VHA) databases are used extensively
      to study racial/ethnic disparities; however, these databases may not capture all
      care received by VHA patients. OBJECTIVES: We examined the extent to which
      accounting for non-VHA care changed conclusions about racial/ethnic disparities
      for VHA patients with diabetes. METHODS: Using a cross-sectional observational
      study, we analyzed a national sample of noninstitutionalized Hispanic (n = 5931),
      black (n = 24,670), and white (n = 149,222) VHA patients with diabetes who were
      at least 65 years of age for receipt of annual HbA1c testing, low-density
      lipoprotein (LDL) cholesterol testing, or eye examination from VHA and Medicare
      administrative files. RESULTS: In VHA alone data, adjusting for patient
      characteristics, Hispanic and black patients were as likely as white patients to
      receive HbA1c testing (odds ratio 1.06 [95% confidence interval 0.99-1.13] and
      1.04 [1.00-1.07], respectively), and more likely to receive eye examinations
      (1.31 [1.24-1.38] and 1.33 [1.29-1.37], respectively). Hispanic patients were
      equally likely (1.01 [0.95-1.07]) and black patients were less likely (0.81 [0.79
      0.84]) to receive LDL testing versus white patients. In VHA plus Medicare data,
      Hispanic and black patients were less likely than white patients to receive HbA1c
      (0.76 [0.71-0.82] and 0.83 [0.80-0.87], respectively) and LDL testing (0.84 [0.79
      0.90] and 0.70 [0.68-0.72], respectively), and equally likely to receive eye
      examinations (0.91 [0.86-0.96]) and 0.98 [0.95-1.01]), respectively). Accounting
      for VHA facility had little effect on results. CONCLUSIONS: Restricting to VHA
      data masks racial/ethnic disparities in care of VHA patients. VHA researchers
      must be aware and supplement VHA data with other sources whenever possible.

PMID- 16641663
TI  - The association of physicians' religious characteristics with their attitudes and
      self-reported behaviors regarding religion and spirituality in the clinical
      encounter.
AB  - CONTEXT: Controversy exists regarding whether and how physicians should address
      religion/spirituality (R/S) with patients. OBJECTIVE: This study examines the
      relationship between physicians' religious characteristics and their attitudes
      and self-reported behaviors regarding R/S in the clinical encounter. METHODS: A
      cross-sectional mailed survey of a stratified random sample of 2000 practicing
      U.S. physicians from all specialties. Main criterion variables were self-reported
      practices of R/S inquiry, dialogue regarding R/S issues, and prayer with
      patients. Main predictor variables were intrinsic religiosity, spirituality, and
      religious affiliation. RESULTS: Response rate was 63%. Almost all physicians
      (91%) say it is appropriate to discuss R/S issues if the patient brings them up,
      and 73% say that when R/S issues comes up they often or always encourage
      patients' own R/S beliefs and practices. Doctors are more divided about when it
      is appropriate for physicians to inquire regarding R/S (45% believe it is usually
      or always inappropriate), talk about their own religious beliefs or experiences
      (14% say never, 43% say only when the patient asks), and pray with patients (17%
      say never, 53% say only when the patient asks). Physicians who identify
      themselves as more religious and more spiritual, particularly those who are
      Protestants, are significantly more likely to endorse and report each of the
      different ways of addressing R/S in the clinical encounter. CONCLUSIONS:
      Differences in physicians' religious and spiritual characteristics are associated
      with differing attitudes and behaviors regarding R/S in the clinical encounter.
      Discussions of the appropriateness of addressing R/S matters in the clinical
      encounter will need to grapple with these deeply rooted differences among
      physicians.

PMID- 16641665
TI  - Can Medicare billing claims data be used to assess mammography utilization among
      women ages 65 and older?
AB  - BACKGROUND: Medicare data may be a useful source for determining the utilization
      of mammography among elderly women, but the accuracy of these data has not been
      established. OBJECTIVE: We determined whether Medicare physician billing claims
      are an accurate reflection of mammography utilization among women ages 65 and
      older and whether they can be used to assess the use of screening as compared
      with diagnostic mammography. DATA SOURCES: Mammography use was assessed using
      Medicare billing claims and radiology reports from 2 mammography registries; the
      San Francisco Mammography Registry and the New Mexico Mammography Registry.
      METHODS: Completeness of the Medicare data was assessed by comparing mammography
      use based on Medicare, with radiology reports from the mammography registries,
      which served as the referent standard. Capture rates for Medicare claims for
      individual mammograms were examined, and women were characterized as having
      undergone at least 1 mammogram within each 2-year period based on the Medicare
      data, and these rates were compared with the referent standard. To determine
      whether Medicare data can distinguish between screening and diagnostic
      mammography, we performed a classification analysis using the mammography
      registries screening/diagnostic designation as the referent standard (dependent
      variable) and Medicare claim information as the independent/predictor variable.
      On the basis of the mammogram level classification analysis, women were
      categorized as having been frequently screened (at least 2 screening mammograms
      spaced by 12 to 36 months), screened (at least 1 screening mammogram), or not
      screened. SUBJECTS: Women ages 65 and older, diagnosed with breast cancer between
      1992-1999, who had at least 1 mammogram between 1992-1999 were examined. RESULTS:
      A total of 3340 mammograms were obtained in 1371 women between 1992 and 1999.
      Overall, 83% of mammograms obtained by these women had a corresponding billing
      claim in Medicare. This increased from 65% in 1992 to 90% in 1999. Of women who
      underwent at least 1 mammogram during each 2-year period per the referent
      standard, 94% of women were accurately classified by Medicare claims as also
      having undergone mammography during the same 2-year period. In multivariable
      analysis, a mammogram was more likely to be associated with a billing claim over
      time, for women 80 years or older, and for white and Asian as compared with
      Hispanic women. Neither socioeconomic status nor screening/diagnostic designation
      affected the likelihood that a mammogram would be associated with a billing
      claim. The Medicare data accurately categorized a given mammogram as screening or
      diagnostic for 87.5% of mammograms. Lastly, there was moderate to substantial
      agreement in the categorization of women as frequently screened, screened or not
      screened between the 2 data sets (weighted kappa 0.74, 95% confidence interval
      0.70-0.78). CONCLUSION: Medicare administrative claims are reliable for
      assessment of mammography utilization and have become more accurate over time.
      Medicare claims data also provide a mechanism for designating mammography as
      screening or diagnostic, which subsequently may allow accurate description of a
      woman's screening history.

PMID- 16641664
TI  - A propensity score analysis of brief worksite crisis interventions after the
      World Trade Center disaster: implications for intervention and research.
AB  - BACKGROUND: Postdisaster crisis interventions have been viewed by some as
      appropriate to enhance the mental health status of persons affected by large
      scale traumatic events. However, studies and systematic reviews have challenged
      the effectiveness of these efforts. OBJECTIVES: The focus of this study was to
      examine the impact of brief mental health interventions received by employees at
      the worksite after the World Trade Center disaster (WTCD) among workers in New
      York City (NYC). RESEARCH DESIGN: The data for the present study come from a
      prospective cohort study of 1121 employed adults interviewed by telephone in a
      household survey 1 year and 2 years after the WTCD. All study participants were
      living in NYC at the time of the attacks. For the current study, we used
      propensity scores to match intervention cases (n = 150) to nonintervention
      controls (n = 971) using a 1:5 matching ratio based on a bias-corrected nearest
      neighbor algorithm. RESULTS: Approximately 7% of NYC adults (approximately
      425,000 persons) reported receiving employer-sponsored, worksite crisis
      interventions related to the WTCD provided by mental health professionals. In
      addition, analyses indicated that attending 1 to 3 brief worksite sessions was
      associated with positive outcomes up to 2 years after the WTCD across a spectrum
      of results, including reduced alcohol dependence, binge drinking, depression,
      PTSD severity, and reduced anxiety symptoms. CONCLUSIONS: Although our study had
      limitations, it is one of the few to suggest that brief postdisaster crisis
      interventions may be effective for employees after mass exposure to
      psychologically traumatic events. The reasons for the effectiveness of these
      interventions are unclear at this time and warrant further investigation.

PMID- 16641666
TI  - Validity of a prescription claims database to estimate medication adherence in
      older persons.
AB  - BACKGROUND: Prescription claims data have been used to estimate refill medication
      adherence through calculations of cumulative medication acquisition (CMA) and
      cumulative medication gap (CMG) values. Few studies have assessed the validity of
      these calculated rates. OBJECTIVES: We sought to assess the validity of CMA and
      CMG calculated from the Manitoba prescription claims database (DPIN) against pill
      count medication adherence, targeting overall medications and angiotensin
      converting enzyme inhibitors (ACEIs). METHODS: Using a survey of a convenience
      sample of subjects recruited through community pharmacies, subjects who were
      eligible for study (ie, 65 years or older, noninstitutionalized, taking 2 or more
      "discrete" prescribed medications, including an ACEI, and willing to provide
      informed consent) were studied. Pill counts were conducted on all prescribed
      medicines during 3 home interviews over the course of 4 months. Ten months of
      DPIN data also were collected on each subject. RESULTS: The concordance between
      CMA and pill count for overall medications was 411/522 (79%) and for ACEIs was
      89/101 (88%) with no systematic differences (McNemar's P = 0.68 and P = 0.097,
      respectively). CMG and pill count showed even better concordance of 438/514 (85%)
      for overall medications and 96/101 (95%) for ACEIs, although systematic
      differences were noted for overall medications (McNemar's P = 0.0012) but not for
      ACEIs (McNemar's P = 0.500). Spearman's rank correlations were weak for all
      comparisons. CONCLUSIONS: The high concordance between prescription claims
      database and pill counts suggested that the rate with which patients refill their
      medications usually is consistent with the rate they consume them. DPIN is not
      accurate for nondiscrete dosage forms or medications prescribed for "as-required"
      use.

PMID- 16641667
TI  - Relative disutilities of 47 risk factors and conditions assessed with seven
      preference-based health status measures in a national U.S. sample: toward
      consistency in cost-effectiveness analyses.
AB  - BACKGROUND: Preference-based health measures yield summary scores that are
      compatible with cost-effectiveness analyses. There is limited comparative
      information, however, about how different measures weight health conditions in
      the U.S. population. METHODS: We examined data from 11,421 adults in the 2000
      Medical Expenditure Panel Survey, a nationally representative sample of the U.S.
      general population, using information on sociodemographics (age, gender,
      race/ethnicity, income, and education), health status (EQ-5D, EQ-VAS, and SF-12),
      4 risk factors (smoking, overweight, obesity, and lacking health insurance), and
      43 conditions. From the EQ-5D, we derived summary scores using U.K. [EQ(UK)] and
      U.S. weights. From the SF-12 we derived SF-6D, and regression-predicted EQ-5D
      (U.S. and U.K. weights) and Health Utility Index scores. Each of the 7 preference
      measures was regressed on each of the 47 problems (risk factors and conditions)
      to determine the disutility associated with the problem, adjusting for socio
      demographics. RESULTS: The adjusted disutilities averaged across the 47 problems
      for the 7 preference measures ranged from 0.059 for the SF-6D to 0.104 for the
      EQ(UK). Correlations between each of the measures of the adjusted disutilities
      ranged from 0.85-1.0. Standardization, using linear regression, attenuated
      between measure differences in disutilities. CONCLUSIONS: Absolute incremental
      cost-effectiveness analyses of a given problem would likely vary depending on the
      measure used, whereas the relative ordering of incremental cost-effectiveness
      analyses of a series of problems would likely be similar regardless of the
      measure chosen, as long as the same measure is used in each series of analyses.
      Absolute consistency across measures may be enhanced by standardization.

PMID- 16641668
TI  - Agreement between administrative claims and the medical record in identifying
      patients with a diagnosis of hypertension.
AB  - OBJECTIVE: This study evaluated the accuracy of 2 administrative claims-based
      selection rules to identify patients with hypertension (HTN) using medical
      records as the gold standard. RESEARCH DESIGN: The claims database consisted of
      inpatient, outpatient, pharmacy, and eligibility claims for members of a single
      insurance company from January 2000 through March 2003. Medical records were
      abstracted for 258 matched patient pairs selected by Rule A (at least 1 HTN
      related International Classification of Diseases, 9th Revision [ICD-9] claim) and
      138 pairs selected by Rule B (at least 1 HTN-related ICD-9 and at least 1 HTN
      prescription claim) from 31 provider sites. Sensitivity and specificity of the 2
      selection rules were computed using medical chart review as the gold standard for
      a diagnosis of HTN. SUBJECTS: Of patients selected by Rule A, chart review
      identified 281 patients with and 235 patients without HTN. Of patients selected
      by Rule B, chart review identified 172 patients with and 104 patients without
      HTN. RESULTS: The sensitivity and specificity was 70.8% and 74.9% for Rule A and
      76.2% and 93.3% for Rule B. The kappa score was 0.45 for Rule A and 0.65 for Rule
      B. CONCLUSION: To identify patients with HTN, a selection rule using both a
      diagnosis and prescription claim has greater sensitivity and specificity than a
      rule using a diagnosis claim only.

PMID- 16641669
TI  - Early experiences with e-health services (1999-2002): promise, reality, and
      implications.
AB  - BACKGROUND: E-health services may improve the quality and efficiency of care;
      however, there is little quantitative data on e-health use. OBJECTIVE: The
      objective of this study was to examine trends in e-health use and user
      characteristics. RESEARCH DESIGN: This was a longitudinal study of e-health use
      (1999-2002) within an integrated delivery system (IDS). We classified 4 e-health
      services into transactional (drug refills and appointment scheduling) and care
      related (medical and medication advice) services. SUBJECTS: Approximately 3.3
      million members of a large, prepaid IDS. MEASUREMENTS: Amount and frequency of e
      health use over time and characteristics of users. RESULTS: The number of members
      registered for access to e-health increased from 20,617 (0.7% of all members) in
      Q1 1999 to 270,987 (8.6%) in Q3 2002. Between Q1 and Q3 2002, 42,845 members
      (1.3%) used the drug refill service and 55,901 (1.7%) used the appointment
      scheduling service compared with 10,756 members (0.3%) who used the medical
      advice service and 3069 (0.1%) who used the medication advice service. Over the
      same period, transactional service users averaged 3.5 uses/user versus 1.6
      uses/user among care-related service users. Members most likely to use e-health
      services had a high level of clinical need, a regular primary care provider, were
      30 to 64 years old, female, white, and lived in a nonlow socioeconomic status
      neighborhood. These findings were consistent across e-health service types.
      CONCLUSIONS: Although use of all e-health services grew rapidly, use of care
      related services lagged significantly behind use of transactional services.
      Subjects with greater clinical need and better ties to the health system were
      more likely to use both types of e-health services.

PMID- 16641671
TI  - Differential regulation of tyrosine hydroxylase expression by sonic hedgehog.
AB  - Sonic hedgehog functions to induce floor plate in early stages, and spinal motor
      neurons and midbrain dopaminergic neurons in later stages of development. Here,
      we investigated the effects of sonic hedgehog on tyrosine hydroxylase expression
      in three cell lines that correspond to different stages of neural development.
      Sonic hedgehog increased the tyrosine hydroxylase gene expression in pluripotent
      P19 cells but repressed it in tyrosine hydroxylase-producing PC12 cells. Promoter
      analysis in mouse neural stem cells indicated that the N-terminal of sonic
      hedgehog repressed both the basal and cAMP-dependent protein kinase A-mediated
      tyrosine hydroxylase activity. These results suggest that the N-terminal of sonic
      hedgehog increases tyrosine hydroxylase gene expression in cells to acquire
      dopaminergic phenotypes, but decreases expression in late born neurons by
      antagonizing the protein kinase A cAMP-responsive element binding protein
      pathway.

PMID- 16641670
TI  - Calpain activation in okadaic-acid-induced neurodegeneration.
AB  - Calpain activation has been implicated in the pathogenesis of Alzheimer's
      disease. Okadaic acid, a protein phosphatase-2A inhibitor, has been used in
      Alzheimer's disease research models to increase tau phosphorylation and induce
      neuronal death. We previously reported that okadaic acid induced predominant
      activation of caspase-3 in immature neurons, but less activation in mature
      neurons. We found here that, in okadaic-acid-treated mature neurons, levels of an
      inactive form of m-calpain decreased and levels of calpain-cleaved spectrin and
      synapsin-I fragments increased, suggestive of calpain activation. Pretreatment
      with calpain inhibitor decreased lactate dehydrogenase release by 20% and
      increased average dendritic branch length by 50% compared with neurons treated
      with okadaic acid alone. These findings suggest that calpain is activated during
      okadaic-acid-induced neurodegeneration and calpain inhibition can be protective
      against it.

PMID- 16641672
TI  - Lens epithelial cells promote regrowth of retinal ganglion cells in culture and
      in vivo.
AB  - Lens damage has been demonstrated to promote axonal regeneration of retinal
      ganglion cells. Various mechanisms associated with this enhancement have been
      proposed, including macrophage recruitment and stimulatory factors from the
      lesioned lens. Lens epithelial cells, which become activated as a result of
      injury, are another potential stimulus. A recent study of co-culturing lens
      epithelial cells adjacent to retinal explants without direct contact showed that
      neurites were attracted to grow towards them. We explored the ability of lens
      epithelial cells to act as a favorable substrate for ganglion cell axonal
      regeneration, by culturing retinal explants on top of a lens epithelial cell
      layer, as well as in vivo by transplanting freshly isolated lens epithelial cells
      to the cut optic nerve. Retinal explants cultured on lens epithelial cells
      regenerated more and longer neurites than those cultured on either an acellular
      substrate or a substrate of corneal cells, while lens epithelial cells
      transplanted to the optic nerve stimulated axons to regenerate in close
      association with them.

PMID- 16641673
TI  - Expression levels of vascular endothelial growth factor and its receptors in
      Parkinson's disease.
AB  - Recently, we confirmed the presence of enhanced neural reconstruction in
      Parkinson's disease and in an animal model of Parkinson's disease based on
      increased polysialic acid-like immunoreactivity. Changes in neurogenesis often
      appear parallel to changes in angiogenesis. Moreover, both these processes share
      similar modulating factors, like vascular endothelial growth factor (VEGF) and
      its receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1). Using immunohistochemistry, we
      identified in this study upregulation of VEGF in the substantia nigra but not in
      the striatum of patients with Parkinson's disease by enzyme-linked immunosorbent
      assay. Such overexpression may participate in vascular remodeling and
      neurogenesis in the substantia nigra of Parkinson's disease.

PMID- 16641674
TI  - Age-related reexpression of p75 in axotomized motoneurons.
AB  - p75 was immunohistochemically identified in spinal motoneurons in immature and
      adult rats after either distal peripheral axotomy or root avulsion. Few or no p75
      positive motoneurons were observed after distal axotomy in animals at the age of
      postnatal day 1 and postnatal day 7, whereas the injury induced marked neuronal
      death. Motoneurons reexpressed p75 from the end of the second postnatal week to
      adulthood in response to distal axotomy, whereas most motoneurons survived after
      the injury. On the other hand, root avulsion in animals of all ages did not cause
      significant p75 expression in avulsed motoneurons where most motoneurons died
      ultimately. The potential role of such reexpression in motoneuron protection is
      discussed.

PMID- 16641675
TI  - Thalamic calcification in vitamin D receptor knockout mice.
AB  - Vitamin D is a steroid hormone with many important functions in the brain,
      mediated through the nuclear vitamin D receptor. Here, we report that aging
      nuclear vitamin D receptor knockout mice demonstrate a symmetric thalamic
      calcification with numerous Ca/P-containing laminated bodies. These results are
      consistent with clinical findings showing brain calcification in patients with
      vitamin D deficiency. Our results suggest that nuclear vitamin D receptor
      deficiency leads to brain mineralization in vitamin D receptor knockout mice,
      which may represent an experimental model of intracranial calcification.

PMID- 16641676
TI  - Why Cyclops could not compete with Ulysses: monocular vision and mental images.
AB  - The present research demonstrates that the limitations of congenitally blind
      people in tasks requiring the processing of mental images are specifically
      related to the absence of binocular vision and not to the absence of vision per
      se. We contrasted three different groups of participants: sighted; visually
      impaired, with reduced binocular vision; monocular, with a normal visual acuity
      although in one eye only. Visually impaired participants (i.e. blurred vision)
      show a pattern of performance comparable to that of the sighted. In contrast,
      monocular participants show a similar pattern of performance to congenitally
      blind individuals despite being able to see perfectly well. These results shed
      new light on the relationship between perception and imagery and on the
      characteristics of sequential and simultaneous processes in the human brain.

PMID- 16641677
TI  - Is bilingual lexical access influenced by language context?
AB  - Using primed lexical decision, we measured reaction times and event-related brain
      potentials to targets that had German meanings (boss) of German-English
      interlingual homograph primes (chef). In an all-English experiment, we tested the
      effects of (1) global language context created by a first- or second-language
      film before the experiment, and (2) context over time, by analyzing the first and
      second experimental halves. We report significant reaction time and event-related
      potential priming of first-language meanings in the second-language experiment.
      The effects obtained despite block and context manipulations support and extend
      the nonselective access theory of bilingual word recognition.

PMID- 16641678
TI  - Intraparaventricular neuropeptide Y and ghrelin induce learned behaviors that
      report food deprivation in rats.
AB  - Rats were trained to discriminate between 2 and 22-h food deprivation in a choice
      paradigm. During tests, 20 min of food consumption eliminated internal stimuli
      associated with 22-h food deprivation. In other tests, rats food-restricted for 2
      h were given neuropeptide Y or ghrelin by administration into the paraventricular
      nucleus of the hypothalamus. Both neurochemicals induced effects similar to those
      following 22-h food restriction (increased behavior appropriate for 22-h
      deprivation). These findings suggest that internal stimuli produced by 22-h food
      deprivation are altered by food consumption and mimicked by feeding-inducing
      neurochemicals administered into a brain area associated with feeding regulation.
      Thus, hunger discrimination is a useful model to examine neurochemical and
      dietary factors that alter internal states associated with eating.

PMID- 16641679
TI  - Spatial frequency-specific potentiation of human visual-evoked potentials.
AB  - Recent research has suggested that cortical long-term potentiation can be induced
      non-invasively in humans by using rapid visual stimulation. The present study
      extends these findings by investigating the specificity of this long-term
      potentiation effect to the inducing stimulus. One group of study participants
      were tetanized using a one cycle-per-degree sine grating, while a second group
      was tetanized using a five cycles-per-degree sine grating. Using
      electroencephalography, we found that an increase in the N1b potential was
      specific to sine gratings of the same frequency as the tetanus. No effect was
      observed in the N1b for sine gratings of a different spatial frequency. These
      results suggest that the long-term potentiation effect induced by the sensory
      tetanus is isolated to a discrete neural population in the visual cortex.

PMID- 16641681
TI  - Intelligence and information processing during a visual search task in children:
      an event-related potential study.
AB  - To investigate the differences in event-related potential parameters related to
      children's intelligence, we selected 15 individuals from an experimental class of
      intellectually gifted children and 13 intellectually average children as control
      to finish three types of visual search tasks (Chinese words, English letters and
      Arabic numbers). We recorded the electroencephalogram and calculated the peak
      latencies and amplitudes. Our results suggest comparatively increased P3
      amplitudes and shorter P3 latencies in brighter individuals than in less
      intelligent individuals, but this expected neural efficiency effect interacted
      with task content. The differences were explained by a more spatially and
      temporally coordinated neural network for more intelligent children.

PMID- 16641680
TI  - Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677,
      1298 gene polymorphism in Korean schizophrenic patients.
AB  - High homocysteine serum level has been regarded as one of the important factors
      that influence the development of schizophrenia. Genetic variations of
      methylenetetrahydrofolate reductase, which is a main enzyme reducing homocysteine
      level, are reported in schizophrenic patients. We measured the serum level of
      homocysteine/folate and methylenetetrahydrofolate reductase C677T/A1298C gene
      polymorphism in 235 patients with schizophrenia. Plasma homocysteine levels were
      higher and folate levels were lower in patients than in comparison subjects.
      Variations of C677T were more frequent in patients than in comparison subjects.
      Patients with the 677TT genotype showed higher homocysteine levels than patients
      with the CC and CT genotypes. These findings suggest that folate supplement may
      be beneficial to some schizophrenic patients with homocysteinemia due to the
      genetic defect of methylenetetrahydrofolate reductase.

PMID- 16641682
TI  - Acute behavioural stress facilitates long-term depression in temporoammonic-CA1
      pathway.
AB  - Behavioural stress facilitates long-term depression in Schaffer collaterals-CA1
      pathway, but it is unknown whether it influences long-term depression in
      temporoammonic fibres-CA1. Here, we report that low-frequency stimulation induced
      long-term depression and foot shock stress before slice preparation facilitated
      long-term depression in both pathways of young rat slices. When the field
      excitatory postsynaptic potentials were recorded by stimulating the two pathways
      alternately and low-frequency stimulation was given to the two pathways
      simultaneously, a reliable long-term depression was induced in Schaffer
      collaterals-CA1 but a reliable long-term potentiation took place in
      temporoammonic fibres-CA1. Interestingly, foot shock stress now enabled low
      frequency stimulation to induce reliable long-term depressions in both pathways.
      These findings suggested that acute behavioural stress facilitated long-term
      depressions in both pathways and disrupted the interactions between pathways.

PMID- 16641685
TI  - Recognizing and managing different types of carditis.

PMID- 16641684
TI  - Recognizing and managing different types of carditis.
AB  - Get a beat on endocarditis, myocarditis, and pericarditis.

PMID- 16641686
TI  - Striking back at heparin-induced thrombocytopenia.
AB  - This immune reaction to a common anticoagulant can have devastating consequences.
      Learn how to recognize who's at risk and how to intervene if trouble hits.

PMID- 16641687
TI  - Getting to the heart of cardiomyopathies.
AB  - Find out about the four types and how to help your patient manage signs and
      symptoms.

PMID- 16641688
TI  - For new CPR guidelines, think 30.

PMID- 16641689
TI  - How to provide transcutaneous pacing.
AB  - Learn how temporary noninvasive cardiac pacing can protect your patient until
      normal conduction is restored or he receives a transvenous pacemaker.

PMID- 16641690
TI  - Take charge with an automated external defibrillator.
AB  - Prepare to act quickly when a patient suddenly becomes unresponsive.

PMID- 16641691
TI  - Heads up on cerebral bleeds.
AB  - Bleeding in the brain can be difficult to pinpoint and may mimic other
      conditions. Learn how to help your patient get an accurate diagnosis and
      appropriate treatment quickly.

PMID- 16641694
TI  - Can you recognize serotonin syndrome?

PMID- 16641693
TI  - Everybody out!
AB  - Will your facility's evacuation procedures withstand a disaster?

PMID- 16641695
TI  - Bleeding in pregnancy: what's the diagnosis?
AB  - Is it placenta previa or abruptio placentae? Find out the key differences and how
      they affect your plan of care.

PMID- 16641696
TI  - The one that didn't get away.
AB  - My part in a lifesaving drama was small... or so I thought.

PMID- 16641697
TI  - Avoiding a crowd in the ED.
AB  - Suffering from a lack of beds? Don't take it lying down.

PMID- 16641698
TI  - Is it a kidney stone or abdominal aortic aneurysm?
AB  - Signs and symptoms of these two conditions can be very much alike-but one
      disorder can be fatal if not treated promptly. Here's what you need to know.

PMID- 16641699
TI  - Procainamide: Test your drug IQ.
AB  - Learn how to safely give this treatment for ventricular arrhythmias.

PMID- 16641700
TI  - Infantile fibrosarcoma of the hand associated with coagulopathy.
AB  - BACKGROUND: Large congenital neoplasms of the extremities may be associated with
      coagulopathies and significant hemorrhage in the neonatal period. At times, the
      differences between coagulation derangements can be very subtle, leading to
      errors in diagnosis. Infants with vascular lesions and coagulopathies are often
      found to have the Kasabach-Merritt phenomenon, which is a platelet-trapping
      coagulopathy. However, other neoplasms or vascular malformations can be
      accompanied by disseminated intravascular coagulation. It is important to obtain
      accurate diagnoses of the neoplasm and the coagulopathy because the treatments of
      similar-appearing tumors and coagulopathies can be markedly different. METHODS:
      The authors report the case of a newborn with a congenital tumor of the left hand
      that was accompanied by a coagulopathy that caused significant bleeding. RESULTS:
      A presumption was made by the neonatal critical care physicians and hematologists
      that the infant had a kaposiform hemangioendothelioma along with the Kasabach
      Merritt phenomenon. However, steroid treatment did not reduce the size of the
      mass or correct the coagulopathy. Only after obtaining consultation with a hand
      surgeon and a tissue diagnosis was it learned that the patient had an infantile
      fibrosarcoma that was accompanied by disseminated intravascular coagulation. Limb
      sparing resection of the lesion along with chemotherapy markedly improved the
      patient's condition. CONCLUSIONS: Large congenital neoplasms presenting with
      attendant bleeding diatheses must be rapidly and accurately diagnosed with both a
      biopsy-proven tissue diagnosis and a hematologic characterization of the nature
      of the coagulopathy. The differential diagnosis of a vascular-appearing mass in
      the extremity can be subtle, and presumptive diagnosis, as occurred in this case,
      can lead to incorrect or delayed treatment. Specifically, kaposiform
      hemangioendothelioma must be differentiated from infantile fibrosarcoma. The
      principles of infantile fibrosarcoma treatment are limb-sparing resection and
      chemotherapy.

PMID- 16641701
TI  - Effective surgical treatment of cubital tunnel syndrome based on provocative
      clinical testing without electrodiagnostics.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe a method of clinical evaluation for accurate diagnosis of ulnar
      compression syndrome at the elbow. 2. Evaluate the accuracy and efficacy of the
      described method in diagnosing surgically correctable nerve entrapment. 3.
      Present a protocol for conservative management followed by surgical correction.
      4. Discuss the results of the method and protocol in two series of patients
      treated by a single surgeon. BACKGROUND: This study of two patient populations
      addresses the effectiveness of identifying surgically correctable ulnar nerve
      compression at the elbow based on provocative clinical testing alone in patients
      with cubital tunnel syndrome after failure of conservative treatment. METHODS:
      Twenty-four patients were included in the preliminary study (mean age, 60 years).
      Three of these patients underwent bilateral procedures. Patients complaining of
      symptoms in the distribution of the ulnar nerve were tested by elicitation of
      Tinel's sign and combined flexion and pressure testing at the elbow and wrist.
      Two-point discrimination was determined. After a failed 6-week trial of
      conservative therapy, patients underwent anterior submuscular transposition of
      the ulnar nerve with carpal tunnel release. RESULTS: Postoperatively, the change
      in two-point discrimination as measured at 6 months was significantly improved,
      with a mean improvement per digital nerve of 2.52 mm (p < 0.001). Mean time to
      relief was 7.2 weeks. Complications included one hematoma and one seroma. A total
      of 26 of the 27 limbs chosen for surgical treatment by provocative clinical
      testing alone experienced relief of symptoms with anterior submuscular
      transposition of the ulnar nerve and carpal tunnel release. CONCLUSIONS: This
      study demonstrates the effectiveness of surgical therapy in patients with lesions
      identified by clinical examination without electrodiagnostic testing. After the
      completion of this study, an additional 87 patients were treated (18 bilateral)
      with cubital tunnel release. The data from these patients confirm the
      effectiveness of surgical treatment of ulnar entrapment neuropathy based on
      provocative clinical testing.

PMID- 16641702
TI  - Breast cancer local recurrence after mastectomy and TRAM flap reconstruction:
      incidence and treatment options.
AB  - BACKGROUND: The transverse rectus abdominis musculocutaneous (TRAM) flap is the
      standard in autologous breast reconstruction. The management of local recurrence
      of breast cancer after TRAM flap breast reconstruction has not been well
      described. The purpose of this study was to examine the incidence of local
      recurrence of breast cancer after TRAM flap breast reconstruction, evaluate
      treatment modalities, and determine outcomes in such cases. METHODS: A
      retrospective review was conducted of all patients who underwent immediate breast
      reconstruction with a free or pedicled TRAM flap over a 15-year period. Those
      patients who experienced local breast cancer recurrence were identified. A subset
      of complete skin-sparing mastectomy patients was also identified for review.
      RESULTS: From 1987 to 2002, 419 TRAM flap breast reconstructions were performed
      in 395 patients. Thirty-four (9 percent) were complete skin-sparing mastectomy
      using a periareolar mastectomy incision only. The mean follow-up time in this
      study was 4.9 years (range, 1 to 14.7 years). Local recurrence occurred in 16 of
      419 patients (3.8 percent), with a mean time to local recurrence of 1.6 years
      (range, 0.2 to 7.0 years). There were no local recurrences seen in patients
      following complete skin-sparing mastectomy. Treatment of local recurrence
      included excision, chemotherapy, radiotherapy, and bone marrow transplant. Only
      three of the 16 patients (19 percent) required removal of the entire TRAM flap to
      manage local breast cancer recurrence. Nine of 16 patients (56 percent) with
      local recurrence died of disease at a mean of 1.2 years after the development of
      recurrence. CONCLUSION: Long-term follow-up demonstrated a local recurrence rate
      after TRAM flap breast reconstruction similar to that reported in the literature.
      Local recurrence was effectively managed with surgical excision of the involved
      tissues, chemotherapy, and/or radiation therapy. Removal of the entire TRAM flap
      was only necessary in the setting of multifocal recurrence or involvement of the
      flap pedicle with disease. The risk of local recurrence was not increased
      following complete skin-sparing mastectomy.

PMID- 16641703
TI  - Evaluation of late results in breast reconstruction by latissimus dorsi flap and
      prosthesis implantation.
AB  - BACKGROUND: Breast reconstruction by latissimus dorsi myocutaneous flap in
      combination with a prosthesis is a widely used, well-established procedure. Short
      and medium-term evaluation after this procedure is well described in the
      literature, but there have been no evaluations of the late course (over 10 years)
      published until now. METHODS: In a retrospective study, 68 patients operated on
      by means of this technique at the authors' institution from 1981 to 1993
      resulting in a minimal follow-up of 10 years were included. Patients were invited
      to an interrogation, clinical examination, and photographic documentation (n =
      51). Incidence of late flap or prosthesis-related complications, number of and
      indications for corrective procedures, and the correlation of the patients'
      subjective judgment and objective results in the late course have been the main
      interest of the authors' survey. RESULTS: The authors found that 50 percent of
      the patients needed a late reoperation for change or removal of the prosthesis.
      Seven (10 percent) of 68 patients needed a definitive removal of the implant in
      the late course. Assessment of the photographic documentation of the late result
      by four nonprofessionals showed that the objective aesthetic results of a
      considerable number of the authors' reconstructions were not sufficient.
      CONCLUSION: The procedure combines two basic techniques of reconstructive
      surgery, the soft-tissue restoration by a pedicled flap as the autologous
      reconstructive component and the volume reconstruction by prosthesis. Therefore,
      these patients are subject to a cumulation of the basic morbidity of the two
      techniques. The authors conclude that the indication for this procedure should be
      restricted to patients not qualifying for "pure" reconstructive techniques.

PMID- 16641704
TI  - Breast reconstruction using the entire transverse abdominal adipocutaneous flap
      based on unilateral superficial or deep inferior epigastric vessels.
AB  - BACKGROUND: Among various alternatives for autologous breast reconstruction, the
      superficial inferior epigastric artery abdominal flap provides the least donor
      site morbidity, as dissection of the rectus abdominis sheath and muscle is not
      required. However, because of inconsistencies in the existence and size of the
      superficial inferior epigastric artery, its use is limited. In addition, whether
      the perfusion from the superficial system is adequate across the midline is still
      a question to be answered. METHODS: Over a period of 16 months, the authors
      performed a total of 44 breast reconstructions using either the deep inferior
      epigastric artery perforator flap (n = 30) or the superficial inferior epigastric
      artery flap (n = 14). In all cases, the superficial inferior epigastric artery
      system was explored first and used as the pedicle if the diameter of the
      available vessels was larger than 1 mm. If the vessels were unavailable or the
      diameters were smaller than 1 mm, the deep inferior epigastric artery and vein
      were used as the pedicle. The diameter of the superficial inferior epigastric
      artery ranged between 0.8 and 3.0 mm, and the mean pedicle length was 6 cm. The
      superficial inferior epigastric artery was not available in 21 cases (48
      percent), and in nine cases (20 percent) the diameter was smaller than 1 mm. In
      six cases where the superficial inferior epigastric artery was judged to be
      appropriate, laser Doppler study was performed perioperatively to assess the
      perfusion of each zone (I through IV) from the deep and superficial systems
      consecutively. In all cases, the superficial and deep systems ipsilateral to the
      defect were dissected. During inset, zone IV was not discarded routinely, and
      92.3 percent and 86.7 percent of the harvested superficial inferior epigastric
      artery flap and deep inferior epigastric artery perforator flap, respectively,
      were used. RESULTS: The flap survival rates were 93 and 100 percent in the
      superficial inferior epigastric artery and deep inferior epigastric artery
      perforator groups, respectively. Adequate perfusion of all zones from the
      superficial system was documented by laser Doppler flowmetry, and the perfusion
      rates were comparable to the deep system. CONCLUSIONS: The entire abdominal
      adipocutaneous flap based on the unilateral superficial inferior epigastric
      artery is as reliable as one based on the deep inferior epigastric artery
      perforator flap. As a result, initially, the superficial inferior epigastric
      artery flap should be explored, as it provides less donor-site morbidity. A
      sizable superficial artery and vein is sufficiently safe for microsurgical
      transfer, similar to the deep inferior epigastric system.

PMID- 16641706
TI  - Insetting of the superficial inferior epigastric artery flap in breast
      reconstruction.

PMID- 16641707
TI  - A clinical retrospective study comparing two short-scar face lifts: minimal
      access cranial suspension versus lateral SMASectomy.
AB  - BACKGROUND: The purpose of this study was to retrospectively compare the short-
      and long-term cosmetic outcomes of two minimal incision rhytidectomies and
      analyze their advantages and disadvantages. METHODS: The results of minimal
      access cranial suspension face lift versus minimal incision rhytidectomy with
      lateral SMASectomy were evaluated after 1 and 24 months. Statistical analysis
      considered surgeon/patient satisfaction, time used in the procedures, pain, and
      learning curves. Photographs were sent to the patients and two plastic surgeons,
      unfamiliar with the cases, for evaluation of results that were assessed by an
      objective grading system described by Strasser. RESULTS: Eighty-two patients
      completed 1 and 24 months' follow-up. Complications were two hematomas, two
      retroauricular-lobule dog-ears, and one hypertrophic preauricular scar. Surgical
      time was longer for the SMASectomy. Postoperative pain was worse for minimal
      access cranial suspension face lift. There were no differences in cosmetic
      results between the two techniques at 1-month and 2-year follow-up. Incorporating
      age, sex, postoperative pain, and duration of surgery as confounding factors did
      not modify the model. Surgeon/patient satisfaction showed no difference with
      either technique, but the photographic evaluation of all cases at 24 months
      revealed that more than 50 percent of the sample needed a tuck procedure to
      correct jowling and redundant skin. CONCLUSIONS: Advantages of short-scar face
      lifts are the avoidance of the postauricular and occipital incisions, and the
      disadvantages are the moderate results in the neck and nasolabial folds and their
      potential short duration. For 24 months in this study, the duration of results
      was similar for both minimal access cranial suspension and lateral SMASectomy.

PMID- 16641709
TI  - Correction of blepharophimosis with silicone implant suspensor.
AB  - BACKGROUND: Blepharophimosis is a rare autosomal-dominant syndrome involving the
      periorbital region. It is characterized mainly by eyelid ptosis, palpebral
      phimosis, telecanthus, and epicanthus inversus. METHODS: Ten patients ranging in
      age from 2 to 22 years who presented with blepharophimosis were retrospectively
      studied over the past 14 years; they had an average follow-up of 7 years and 5
      months. They were treated at the Division of Plastic Surgery of the Faculty of
      Medicine, University of Sao Paulo. Eight patients presented with the complete
      form, including epicanthus, telecanthus, and severe palpebral ptosis, and two
      presented with the incomplete form. The epicanthi and telecanthi were corrected
      with Mustarde's technique, and the ptosis was treated by frontalis suspension
      with a soft, preformed silicone device called the silicone implant suspensor.
      RESULTS: The results were classified as good, fair, and poor, according to the
      postoperative position of the upper eyelid in relation to the scleral limbus,
      medial canthus position, and residual epicanthal fold. The results were assessed
      as good in seven cases and fair in three. CONCLUSIONS: The silicone eyelid
      suspensor was effective in improving the patients' difficult condition. It was a
      better alternative than the use of fascia lata, because it permitted an easier
      readjustment of the eyelid margin and it offered the possibility of creating a
      well-defined palpebral fold, which is usually absent in this group. The results
      were maintained with long-term follow-up. The silicone suspensor was safe and
      long-term results were good in both children and adults.

PMID- 16641711
TI  - Use of pedicled local flaps for male chest augmentation and reshaping.

PMID- 16641710
TI  - The genioplasty and beyond: an end-game strategy for the multiply operated chin.
AB  - BACKGROUND: Genioplasty has been a useful and frequently employed technique. In
      previous publications, the authors discussed the benefits and versatility of the
      genioplasty. Here, they briefly examine the entire experience of the senior
      author, from 1975 to the present. METHODS: The authors examined a series of 580
      genioplasties performed in 567 patients over a 28-year period by the senior
      author. This was done by chart review, which involved collection of demographic
      data and tabulation of the number of operations and type of genioplasty, as well
      as inspection of operative notes and clinical photographs. The focus was on the
      subgroup of patients who required multiple procedures to obtain a final
      satisfactory result. In one subgroup of patients, largely those with severe
      developmental or syndromic retrogenia, staged procedures were part of the
      original plan. A second subgroup included patients who had had problems with
      alloplastic chin implants; for these patients, further operations were not part
      of the original plan. RESULTSIn the first group of patients, with severe
      developmental or syndromic retrogenia, an osseous genioplasty was often
      associated with orthognathic surgery and could be repeated later as a staged
      procedure. In the second group of patients, who had multiple problems with
      alloplastic chin implants, an osseous genioplasty often provided the solution to
      difficult problems. CONCLUSIONS: In both groups of patients, an autogenous costal
      cartilage graft may be of great help after one has accomplished as much as one
      can with an osseous genioplasty. In rare cases, microsurgical free tissue
      transfer may be required.

PMID- 16641713
TI  - Neurovascular transfer does not cause skeletal muscle fiber degeneration.
AB  - BACKGROUND: The mechanisms responsible for the incomplete recovery of muscle
      function after microneurovascular transfer have not been fully determined.
      Because fiber degeneration and regeneration can impact muscle mechanical
      function, the authors tested the null hypothesis that ischemia-induced fiber
      degeneration is not responsible for the force deficits observed after
      neurovascular muscle transfer. METHODS: Rats were assigned to one of three
      groups: orthotopic, nonvascularized grafting of the extensor digitorum longus
      muscle (STD group); orthotopic, neurovascular transfer of the extensor digitorum
      longus muscle with no intraoperative ischemia (NV-0 group); or orthotopic,
      neurovascular transfer of the extensor digitorum longus muscle with 3 hours of
      intraoperative ischemia (NV-3 group). At 1 and 2 weeks, extensor digitorum longus
      muscle cross-sections were labeled for developmental myosin heavy chain isoforms,
      markers of fiber regeneration. RESULTS: In extensor digitorum longus muscles from
      animals in the STD group, many small cells strongly labeled for developmental
      myosin heavy chain were observed and identified as myoblasts, indicating recent
      muscle fiber necrosis with subsequent regeneration. Extensor digitorum longus
      muscles from rats in the NV-0 and NV-3 groups contained no cells labeled for
      developmental myosin heavy chain. CONCLUSIONS: After neurovascular muscle
      transfer (with ischemia times up to 3 hours), ischemia-induced muscle fiber
      degeneration and regeneration does not occur. Muscle fiber degeneration is not
      responsible for the force deficits observed after microneurovascular skeletal
      muscle transfer.

PMID- 16641714
TI  - Comparison of osteogenic potentials of visceral and subcutaneous adipose-derived
      cells of rabbits.
AB  - BACKGROUND: The demand for a large amount of osteogenic cells required in bone
      tissue engineering warranted exploration of a new source of osteoprogenitor
      cells. Recent studies have demonstrated that adipose-derived stromal cells
      possess multiple differentiation capacities, including osteogenic potential, as
      bone marrow mesenchymal stem cells. In the present study, the authors compared
      the osteogenic potentials of adipose-derived stromal cells from different
      anatomical sites of rabbits. METHODS: Different adipose-derived stromal cells
      were isolated from rabbit visceral and subcutaneous adipose tissues by enzymatic
      digestion and in vitro differentiation into osteogenic lineage. Osteogenic
      markers representing differentiation potentials of adipose-derived stromal cells
      from different anatomical sites were compared by biochemical and
      immunohistochemical assessment (n = 3). RESULTS: Fibroblast-like cells were
      digested from both visceral and subcutaneous adipose tissues. After exposure to
      osteogenic differentiation medium, visceral adipose-derived cells were found to
      possess greater osteogenic potentials than cells isolated from subcutaneous
      adipose tissues, evidenced by significantly different amounts of osteogenic
      markers including alkaline phosphatase, osteocalcin, and mineral deposition.
      CONCLUSION: This study indicates that osteogenic potentials of adipose-derived
      cells vary by their anatomical sites, with visceral adipose-derived cells
      exhibiting higher osteogenic potential than those isolated from subcutis.
      However, the mechanism is still unidentified.

PMID- 16641715
TI  - Experimental study of vascularized tissue-engineered bone grafts.
AB  - BACKGROUND: Vascularized bone grafting has become a useful method for treatment
      of large bone defects and infected nonunions that lack adequate blood supply.
      This method has disadvantages, however, such as donor-site complications. To
      overcome these disadvantages, the authors developed a new method for creating
      vascularized tissue-engineered bone grafts in an experimental model. METHODS:
      Fisher rat bone marrow mesenchymal stem cells were cultured for 2 weeks in fully
      opened, interconnected, porous hydroxyapatite ceramic. The composites of
      mesenchymal stem cells and hydroxyapatite were implanted in the medial calf
      region together with the saphenous vascular bundle in syngeneic rats. Two weeks
      after implantation, the vascular pedicle with the implants was exposed and
      covered with silicone rubber to prevent vascular invasion through surrounding
      tissues (vascularized mesenchymal stem cell/hydroxyapatite implants). In
      addition, nonvascularized mesenchymal stem cell/hydroxyapatite implants were
      created with a ligated vascular pedicle. Implants of vascularized hydroxyapatite
      alone were prepared as a control. All implants were retrieved 4 weeks after
      surgery. RESULTS: Histologically, de novo bone formations were observed in the
      vascularized implants. This was in contrast with only necrotic tissue observed in
      the nonvascularized implants. Bone formation was not observed entirely in the
      vascularized hydroxyapatite-alone implants. For biochemical analysis, alkaline
      phosphatase activity and osteocalcin content of the vascularized mesenchymal stem
      cell/hydroxyapatite implants were significantly higher than those of the
      nonvascularized mesenchymal stem cell/hydroxyapatite and vascularized
      hydroxyapatite-alone implants. CONCLUSION: The results of this study indicated
      that the vascularized tissue-engineered bone grafts could be transferred as free
      vascularized grafts to lesions that lack adequate blood supply.

PMID- 16641716
TI  - Brachial artery thrombosis in infants: an algorithm for limb salvage.
AB  - BACKGROUND: Arterial occlusion in infants, although uncommon, is usually an
      iatrogenic event associated with arterial vascular access. Most common in the
      upper limb, the consequences of iatrogenic arterial occlusion may be gangrene and
      limb loss. Even if there is adequate collateral flow and limb loss is avoided,
      long-term growth disturbances may be seen. There are few published data to guide
      the management of arterial occlusion in premature or sick infants. In general,
      there is agreement regarding the importance of early diagnosis and the
      reestablishment of limb perfusion with the fewest risks, but the optimal choice
      and timing of treatment modalities remain unknown. METHODS: This article examines
      the authors' experiences at the Royal Children's Hospital, Melbourne, and
      provides their algorithm for the management of this complex iatrogenic disease.
      RESULTS: The management algorithm has successfully treated 11 limbs in 11
      patients with arterial vascular access-associated thrombosis over the period 1995
      to 2003, with no instances of limb loss. Five of these patients required surgical
      intervention. CONCLUSIONS: The authors recommend a multidisciplinary approach
      involving plastic surgeons and hematologists for all cases of suspected or
      confirmed arterial thrombosis. A consensus algorithm that determines the role of
      heparin, thrombolysis, and acute surgical interventions, and the sequence of such
      interventions, is useful in providing the framework of therapy. The early
      recognition of the limb at risk is a key factor in obtaining a successful
      outcome.

PMID- 16641717
TI  - The use of suture strips to aid reduction of fractures of the hand.

PMID- 16641718
TI  - Surgical correction of velopharyngeal insufficiency in children with
      velocardiofacial syndrome.
AB  - BACKGROUND: The surgical management of velopharyngeal insufficiency in children
      with velocardiofacial syndrome is inherently more difficult, with the need for
      revision being high. The purpose of this report was to evaluate and document the
      authors' experience with sphincter pharyngoplasty in the management of
      velopharyngeal insufficiency in children with velocardiofacial syndrome, and
      compare outcome. METHODS: In part I, 32 patients with velocardiofacial syndrome
      underwent sphincter pharyngoplasty for velopharyngeal insufficiency between
      January of 1987 and March of 2001. There were 18 girls and 14 boys, with a mean
      age at primary sphincter pharyngoplasty of 6.7 years. Pharyngoplasty revision was
      defined as any secondary surgical revision of the sphincter as determined by
      clinical evaluation and objective speech assessment. In part II, comparisons were
      made to 218 non-velocardiofacial syndrome patients with velopharyngeal
      insufficiency who underwent sphincter pharyngoplasty (cleft palate, n = 127;
      velopharyngeal insufficiency alone, n = 63; submucous cleft, n = 15; other, n =
      13). There was no significant difference in the average age or gender in the two
      groups. All patients underwent screening of velopharyngeal function, which
      included perceptual speech evaluation, clinical screening of velopharyngeal
      closure, and oral examination. RESULTS: In part I, success of the primary
      sphincter pharyngoplasty was demonstrated in 78 percent of the velocardiofacial
      syndrome patients (n = 25), with a revision rate of 22 percent. Patients who
      required revision were slightly older, 8.6 versus 6.3 years (p = not
      significant). Preoperative nasometry scores were significantly higher in patients
      who required a pharyngoplasty revision (69 versus 54; p = 0.002). Patients who
      required revision of the pharyngoplasty were more likely to have larger
      velopharyngeal areas (30 mm versus 22 mm). In part II, the revision rate in
      patients with velocardiofacial syndrome was significantly higher than in those
      patients in the original cohort without velocardiofacial syndrome (22 percent
      versus 11 percent; p < 0.05). Preoperative objective speech data demonstrated
      significantly greater velopharyngeal incompetence in all categories (nasometry
      scores, pressure flow measurements, and radiographic measurements) for patients
      with velocardiofacial syndrome, and age at initial sphincter repair was slightly
      older (8.5 versus 7.7 years; p = not significant). CONCLUSIONS: The management of
      velopharyngeal insufficiency using sphincter pharyngoplasty in children with
      velocardiofacial syndrome is safe and effective. The higher need for surgical
      revision in velocardiofacial syndrome patients is most likely attributable to a
      greater degree of preoperative nasalance and a slightly later age of
      presentation. This should provide insight into various technique modifications in
      an attempt to minimize pharyngoplasty revision.

PMID- 16641719
TI  - Improved outcomes in cleft patients with severe maxillary deficiency after Le
      Fort I internal distraction.
AB  - BACKGROUND: Correction of severe maxillary deficiency in cleft lip-cleft palate
      patients often results in undercorrection, relapse, and need for secondary
      corrective procedures. Le Fort I internal distraction osteogenesis offers an
      alternative to one-step orthognathic advancement, with advantages of gradual
      lengthening through scar and earlier treatment in growing patients. METHODS:
      Patients with cleft lip-cleft palate deformities and maxillary deficiency were
      divided into three groups treated by Le Fort I advancement: group 1, mild to
      moderate deficiency (< 10 mm) with conventional orthognathic procedure; group 2,
      severe deficiency (> or = 10 mm) with conventional orthognathic procedure; and
      group 3, distraction procedure for severe deficiency (> or = 10 mm) (n = 51).
      Preoperative, postoperative, and follow-up (> 1 year) lateral cephalogram
      measurements were compared including angular (SNA and SNB) and linear (Deltax =
      horizontal and Deltay = vertical) changes. The Pittsburgh Speech Score was used
      to assess for velopharyngeal insufficiency (score > 3). RESULTS: Results
      demonstrated that group 1 patients had a mean SNA change from preoperatively
      (78.7) to postoperatively (83.8), and a horizontal change of 5.0 mm, with no
      relapse. Group 2 patients had a mean SNA change from preoperatively (76.3) to
      postoperatively (82.0) and a horizontal change of 7.2 mm, with 63 percent
      relapse. Group 3 patients had a mean SNA change from preoperatively (74.1) to
      postoperatively (84.9) and a horizontal change of 16.5 mm, with 15 percent
      relapse. Thus, for severe maxillary deficiency, the distraction group had 48
      percent less relapse than the conventional Le Fort I group. Postoperative speech
      evaluation showed velopharyngeal insufficiency in the following: group 1, four of
      20 patients (20 percent); group 2, nine of 11 patients (82 percent); and group 3,
      nine of 20 patients (45 percent). CONCLUSION: These data suggest that Le Fort I
      internal distraction for severe cleft maxillary deficiency leads to better dental
      occlusion, less relapse, and better speech results.

PMID- 16641720
TI  - Unilateral complete cleft lip and palate repair using lip adhesion combined with
      a passive intraoral alveolar molding appliance: surgical results and the effect
      on the maxillary alveolar arch.
AB  - BACKGROUND: A number of combined maxillary orthopedic and surgical treatment
      protocols have been proposed for the initial phase of therapy for infants with a
      complete cleft lip and palate. METHODS: Lip adhesion was used in combination with
      a passive intraoral molding appliance to treat a unilateral complete cleft lip
      and palate. The proposed protocols are lip adhesion, along with positioning of a
      passive alveolar molding appliance, at 4 to 6 weeks of age, then definitive
      cheiloplasty at 4 to 5 months of age, and palatoplasty at 12 months of age.
      Twenty-five patients with a complete cleft lip and palate were treated using this
      protocol between 1994 and 2003. The follow-up period was between 6 months and 10
      years. RESULTS: The alveolar gap, the length of the maxillary alveolar cleft, and
      the palatal gap were 10.1 +/- 4.2 mm, 6.1 +/- 0.9 mm, and 13.4 +/- 2.9 mm for lip
      adhesion, 3.1 +/- 1.4 mm, 2.6 +/- 0.8 mm, and 9.6 +/- 1.5 mm for definitive
      cheiloplasty, and 0.2 +/- 0.1 mm, 1.5 +/- 0.7 mm, and 8.3 +/- 1.1 mm for
      palatoplasty. For the following maxillary dental casts for 3 to 10 year olds, the
      intercanine width and canine arch lengths were within the normal value. The
      intermolar width and the molar arch length, however, decreased slightly compared
      with the control normal values. CONCLUSIONS: Lip adhesion and a passive alveolar
      molding appliance achieved a normal position and stabilized the arch in a
      symmetrical platform.

PMID- 16641721
TI  - Simultaneous maxillo-mandibular distraction osteogenesis in hemifacial
      microsomia: a new technique using two distractors.
AB  - BACKGROUND: The goal of this study was to prospectively evaluate the use of two
      distractors for a simultaneous maxillo-mandibular distraction osteogenesis
      without the use of intermaxillary fixation in the restorative treatment of
      hemifacial microsomia. METHODS: The authors analyzed the clinical and
      radiological data of five patients with type I hemifacial microsomia (one
      patient), type IIa hemifacial microsomia (two patients), and Goldenhar syndrome
      (two patients). Follow-up examinations were performed at 1, 3, 6, and 12 months.
      RESULTS: All the patients had satisfactory correction of the facial asymmetry
      without complications. Complete horizontalization of the occlusal plane was
      achieved in three patients, whereas a cant of 2 degrees persisted in two
      patients. None of the children in this study were noncompliant with the
      prescribed duration of the active distraction period, nor did they experience
      technical problems with the two devices. CONCLUSIONS: Simultaneous maxillo
      mandibular distraction osteogenesis resulted in a high rate of success in
      correcting facial asymmetry as well as occlusal plane cant. It offered good
      aesthetic satisfaction.

PMID- 16641723
TI  - External filling ports in tissue expansion: confirming their safety and
      convenience.

PMID- 16641724
TI  - One-stage reanimation of the paralyzed face using the rectus abdominis
      neurovascular free flap.
AB  - BACKGROUND: Functional free muscle transfer for the surgical correction of long
      standing facial paralysis has gained validity over the past three decades. These
      traditionally multistep reconstructions often achieve clinical success, but at
      the cost of significant morbidity and lengthy recovery periods. To address this
      dilemma, the authors propose reconstruction using the rectus abdominis and
      accompanying intercostal nerve in a one-stage neurovascular free flap reanimation
      procedure. METHODS: Between 1998 and 2001, five patients with long-standing
      unilateral facial paralysis at the University of Pittsburgh Facial Nerve Center
      underwent reanimation using the authors' protocol. Preoperative and postoperative
      assessments included clinical evaluation using the Facial Grading System and
      electromyography. The patients were followed for a mean of 16 months. RESULTS: At
      the final postoperative visit, all five patients demonstrated improved levator
      electromyographic potential, with a median 67 percent improvement. All five
      patients further demonstrated an increase in zygomaticus electromyographic
      potential, with a median 225 percent improvement. All five patients demonstrated
      increased Facial Grading System score at most recent follow-up. CONCLUSIONS: The
      one-step reanimation using free rectus abdominis neurovascular free flap
      demonstrated a consistent positive outcome in electromyographic and clinical
      assessments. The additional benefits of reduced recovery time and anatomical
      reliability of the flap render the authors' method preferable to other
      traditional methods of surgical reanimation of the paralyzed face.

PMID- 16641725
TI  - Correction of involutional entropion with suborbicularis septal and lateral
      canthal tightening.
AB  - BACKGROUND: Involutional entropion, or infolding of the margin of the eyelid, is
      a common eyelid malposition affecting the elderly that can lead to significant
      morbidity when not corrected. It is notable for both functional and cosmetic
      sequelae. Numerous surgical techniques have been described to correct this
      defect; however, because of its multifactorial pathophysiology, no single
      procedure has been entirely satisfactory. In this study, the authors present a
      simple and effective surgical procedure that addresses the salient
      pathophysiology and successfully corrects this defect with minimal morbidity or
      chance of recurrence. METHODS: Two hundred fifty-three patients (409 eyelids)
      with involutional entropion who underwent surgical repair from 1995 to 2004 were
      analyzed. All patients were symptomatic, ranging in age from 61 to 96 years (115
      men and 138 women). All patients underwent lateral canthal lysis, suborbicularis
      and supraorbicularis undermining, canthoplasty, and lateral muscle suspension
      with septal tightening. RESULTS: All 409 eyelids with symptomatic involutional
      entropion were successfully corrected. All patients were satisfied with both the
      functional and cosmetic outcome and experienced a short recovery time. Objective
      examination revealed a marked improvement in static and dynamic lower eyelid
      position and alleviation of the herniated lateral orbital fat. There were no
      complications or entropion recurrences. CONCLUSIONS: Involutional entropion is
      frequently encountered in the elderly. Ideal treatment addresses horizontal lid
      laxity, improves vertical support, prevents preseptal orbicularis override, and
      reinserts the lower lid retractors. With the direct, easily executed and
      effective surgical procedure presented here, both functional and aesthetic
      improvements can be obtained. This procedure should be included among the
      techniques used by every surgeon who treats functional and cosmetic problems in
      the periocular region.

PMID- 16641727
TI  - Nitrous oxide administered by the plastic surgeon for repair of facial
      lacerations in children in the emergency room.
AB  - BACKGROUND: The purpose of this study was to investigate a means of providing
      pain relief during repair of facial lacerations in children in the emergency
      room. METHODS: This study was conducted in the emergency room of a tertiary care,
      university-affiliated hospital. Fifty percent nitrous oxide was administered by
      the surgeon who sutured the laceration. A nurse monitored the child throughout
      the procedure. At the end of the procedure, pain scores were evaluated by the
      surgeon and nurse using the FLACC (face, legs, activity, cry, and consolability)
      scale, a structured observational-behavioral scale for measurement of pain.
      RESULTS: Sixty patients between the ages of 1 and 16 years participated in the
      study. Of these, 15 were sutured using standard care (lidocaine infiltration),
      and 45 children received nitrous oxide in addition to lidocaine infiltration.
      Nitrous oxide was administered for an average of 11.9 +/- 5.1 minutes (range, 4
      to 30 minutes). Forty-three children recovered to preprocedure activity in less
      than 1 minute. Two children recovered in less than 3 minutes. Average FLACC
      scores during infiltration and suturing were significantly lower in the nitrous
      oxide group compared with controls (infiltration, 1.9 of 10 versus 9.7 of 10;
      suturing, 2 of 10 versus 8.8 of 10). Forceful restraining was necessary in all
      the controls, whereas in the nitrous oxide group mild force was required in only
      15 percent. Seventy percent of the children receiving nitrous oxide had no side
      effects. Vomiting and nausea were the most common (17 percent), transient side
      effects. No respiratory or cardiovascular side effects occurred. CONCLUSIONS:
      Nitrous oxide can be safely administered by plastic surgeons while suturing
      facial lacerations in the emergency room. The fast onset and rapid recovery
      characteristics of nitrous oxide provide a convenient environment for performing
      short surgical procedures. This safe method for provision of analgesia and
      anxiolysis may be appealing to plastic surgeons for ambulatory procedures (e.g.,
      suture removal, expander inflation, Botox injection, injection of various
      fillers) in pediatric and adult populations.

PMID- 16641729
TI  - Prone positioning precautions in plastic surgery.
AB  - Prone positioning carries with it risks associated with neural and vascular
      compression. Meticulous attention to avoiding compression will protect against
      the risks associated with improper positioning, particularly for plastic
      surgeons.

PMID- 16641728
TI  - Reconstruction following radical resection of recurrent metastatic axillary
      melanoma.
AB  - BACKGROUND: Recurrent axillary metastasis following axillary lymphadenectomy for
      melanoma is associated with a poor prognosis. Radical resection of such axillary
      recurrences with concomitant reconstruction may not only yield significant
      palliation of symptoms but also improve disease-free survival. The purpose of
      this study was to evaluate the outcomes of this radical surgical approach and
      help determine the risks and benefits for this patient population. METHODS: A
      retrospective review of all patients who underwent axillary reexcision and
      reconstruction for metastatic melanoma between 1990 and 2000 was conducted at The
      University of Texas M. D. Anderson Cancer Center. Nine patients were identified
      who underwent flap reconstruction following radical excision of axillary
      recurrence after a previous lymphadenectomy. RESULTS: A total of 14 flaps were
      performed on the nine patients (five free flaps and nine pedicled muscle or
      myocutaneous flaps). Indications for surgery included pain, bleeding, and
      infection. Seven of the nine patients received perioperative radiation therapy.
      Palliation of symptoms was achieved in all patients. Free flap survival was 100
      percent. Complications occurred in four of nine patients and included seroma,
      lymphedema, and wound dehiscence. Three patients had second local recurrences
      necessitating reresection and reconstruction; the mean time to rerecurrence was
      6.7 months (range, 2 to 12 months). Four of nine patients were alive with no
      evidence of disease at the end of the follow-up period, with a mean disease-free
      interval of 41 months (range, 5 to 77 months). One patient was alive with distant
      metastasis, and four patients had died of distant metastases. The mean disease
      free interval following original lymphedema for the nine patients was 11 months
      (range, 2 to 40 months). CONCLUSIONS: Aggressive resection of axillary recurrence
      following lymphadenectomy can palliate symptoms in select individuals and may
      result in long-term disease-free survival. Critical to this evolving surgical
      strategy is the use of vascularized soft tissue in the form of pedicled or free
      flaps to provide durable coverage of the resulting resection defect.

PMID- 16641731
TI  - Treatment of recontracture with the subcutaneous pedicle rhomboid flap.
AB  - BACKGROUND: Treatment of recontractures that were previously skin grafted or
      treated with Z-plasty is a challenge. Application of a subsequent Z-plasty is
      risky because of the possibility of tip necrosis of the triangular flaps, whereas
      donor-site morbidity is undesirable if subsequent skin grafting is planned. The
      subcutaneous pedicle rhomboid flap is an effective technique for the treatment of
      every type of contracture. This article presents the clinical results of the
      rhomboid flap used in treatment of recontractures as an alternate technique to Z
      plasty and skin grafting. METHODS: The authors operated on seven patients with
      recontractures (aged 4 to 45 years) using 19 rhomboid flaps. Flaps were applied
      in the upper extremity (seven flaps), lower extremity (five flaps), trunk (five
      flaps), neck (one flap), and axilla (one flap). Z-plasty scars were present in
      three locations, whereas skin grafting was previously applied in 16 locations.
      Preoperative rhomboid flap designs were made regardless of previous scars as
      single flaps in six locations and multiple flaps in 13 locations. Operations were
      performed under local and general anesthesia. RESULTS: Patients were followed up
      for at least 6 months. All flaps achieved adequate relaxation postoperatively and
      healed uneventfully. The subcutaneous pedicle of the flap provided a distinct
      advantage in terms of vascularity. Recurrence was not seen in any of the
      patients. CONCLUSIONS: The subcutaneous pedicle rhomboid flap is an effective and
      reliable technique for the treatment of recontractures. Preoperative planning is
      simple and independent of previous scars. Because the rhomboid flap resurfaces
      the emerged defects generated by relaxation incisions, one should consider that
      the flexibility of a single flap may not be adequate in some cases, and multiple
      flaps should be used.

PMID- 16641732
TI  - Reconstruction of the diabetic foot using the anterolateral thigh perforator
      flap.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome of the diabetic
      foot reconstructed with the anterolateral thigh perforator flap. METHODS: This
      study reviews 71 cases of salvaged diabetic foot over a 52-month period. Patients
      ranged in age from 33 to 72 years (average, 51 years), with an average follow-up
      of 11 months. RESULTS: Flaps survived in all but one reconstructed case,
      resulting in equivocal findings compared with microvascular free tissue transfer
      of nondiabetic patients. Early complications such as delayed healing with minor
      wound dehiscence were seen in three cases, and partial flap necrosis was seen in
      four cases. Patients with chronic infections were controlled without recurrences.
      During the follow-up, 69 patients achieved full weight bearing, acceptable
      contour, and quality of gait before diabetic foot complications. However, late
      complications such as recurrence of ulceration was noted in one patient, who was
      blind and unable to perform daily inspection of the foot. CONCLUSIONS: The
      anterolateral thigh perforator flap provides well-vascularized tissue that
      controls infection, a thin flap that provides one-stage contouring and minimizes
      shearing, and a skin paddle that resists pressure and improves durability. The
      flap can also be combined with vastus lateralis muscle to increase bulk and blood
      supply against large dead spaces and chronic infections. Anterolateral thigh
      perforator flaps can be used to achieve acceptable function and aesthetic results
      for diabetic foot reconstruction.

PMID- 16641733
TI  - New design and identification of the medial sural perforator flap: an anatomical
      study and its clinical applications.
AB  - BACKGROUND: Many studies have revealed facts about the anatomy of the medial
      sural artery perforator. The exact locations or areas where the perforators
      pierce through the fascia, however, have not been clearly identified. METHODS:
      Based on cadaver dissections performed on 40 legs from 20 cadavers, the authors
      identified the location of the first and second perforators of the medial sural
      artery. The passages of the medial sural artery perforators were also confirmed
      by means of duplex-Doppler scanning, three-dimensional computed tomography, and
      angiography. RESULTS: The authors found that the main perforators of the medial
      sural artery were located on a line drawn from the midpoint of the popliteal
      crease to the midpoint of the medial malleolus. The hip joint was flexed in
      supine position and the knee joint was flexed into a 90-degree angle, thus making
      it possible to observe the first perforator, which was approximately 8 cm from
      the midpoint of the popliteal crease, and the second perforator, which was
      approximately 15 cm from the popliteal crease. A series of 21 clinical cases with
      soft-tissue defects were successfully treated using the medial sural artery
      perforator flap, including 18 free flaps and three pedicled flaps. There were
      seven cases of hand reconstruction and 14 cases of lower extremity
      reconstruction. CONCLUSIONS: Until now, it has been a general belief that the
      exact location of a perforator cannot be predicted. The authors, however, have
      found that the first perforator was located almost 8 cm from the midpoint of the
      popliteal crease within the distal half circle drawn with a radius of 2 cm.
      Because this study made it possible to prepare a diagram of the exact location of
      the medial sural perforators, it is expected that more professionals will use
      this method for hand and facial reconstructions in the future.

PMID- 16641734
TI  - Examination of the skin perforators of the posterior tibial artery on the leg and
      the ankle region and their clinical use.
AB  - BACKGROUND: There are many treatment alternatives for reconstruction of leg and
      foot defects. One of these treatment alternatives includes local flaps. A
      detailed understanding of the blood flow of the leg region is essential for
      producing new alternatives for the reconstruction of defects of this region.
      METHODS: The leg and foot region blood flow was examined on 11 fresh cadavers,
      and perforators of this region were examined in three zones. Perforator numbers
      and their diameters were defined at this region. It was determined in cadaver
      studies that especially zones I and II were more suitable for the planned flaps
      based on perforators of the posterior tibial artery. In a clinical study that
      accompanies this anatomical study, eight patients underwent reconstruction by
      flaps based on the perforators of the posterior tibial artery. RESULTS: Patients
      were followed for 3 to 14 months. In three patients, venous drainage problems had
      developed, and in one of them, partial flap loss had developed. This partially
      necrosed region was left to heal by secondary intention. Venous drainage problems
      resolved in 5 to 7 days in the two remaining patients. No other complications
      were seen. CONCLUSION: Regarding the results of the clinical study, the authors
      observed that this flap can provide the desired soft-tissue support for defects
      that expose the bones, tendons, and neural and vascular bundles.

PMID- 16641735
TI  - A new tool for assessing standard of care in medical malpractice cases.
AB  - BACKGROUND: Physician experts hired and prepared by litigants provide most of the
      information on standard of care for medical malpractice cases. Since this
      information may not be objective or accurate, the authors examined the
      feasibility and potential value of surveying peer physicians to assess standard
      of care. METHODS: The survey method for assessing standard of care was evaluated
      for a medical malpractice case involving an abdominoplasty that had a poor
      cosmetic result. An abstract of the case that included the patient's
      characteristics and physician's decisions that were most likely to influence
      patient outcome was created from the transcribed testimony of the plaintiff's
      expert witness. This abstract and a survey that included questions about four
      decisions made by the defendant were sent to 28 plastic surgeons in the Midwest
      who were identified by searches of public documents. RESULTS: Eleven plastic
      surgeons experienced in abdominoplasty completed the survey. Their responses in
      all four areas contrasted sharply with those of the highly credentialed medical
      expert for the plaintiff. CONCLUSIONS: These results suggest that physician
      surveys are feasible and may provide very different results than those from
      expert witnesses about standard of care in medical malpractice cases.

PMID- 16641736
TI  - Go fly a kite!

PMID- 16641738
TI  - Plasmetic surgery.

PMID- 16641739
TI  - Venous thromboembolism in the burn population.

PMID- 16641740
TI  - Puppeteering the umbilicus.

PMID- 16641742
TI  - The medial adiposofascial flap of the leg.

PMID- 16641743
TI  - Topical interferon-alpha2b and keloid treatment: a place for pretreatment?

PMID- 16641744
TI  - Skinhooks for circumscribing the umbilicus during abdominoplasty.

PMID- 16641745
TI  - Vertically split merocel tampon has advantages in nasal packing.

PMID- 16641746
TI  - Hemophilia B diagnosed by hematoma at the columella base.

PMID- 16641747
TI  - Use of a prefabricated titanium plate for accurate reconstruction of secondary
      orbital blow-out fracture.

PMID- 16641748
TI  - An unusual condition of the ear.

PMID- 16641749
TI  - Simple suture technique of securing buccinator myomucosal flaps for the
      reconstruction of large palatal defects.

PMID- 16641750
TI  - Caution note on the use of the internal mammary artery in breast reconstruction.

PMID- 16641751
TI  - Capsulectomy: a mandatory procedure in the presence of capsular calcification.

PMID- 16641752
TI  - A word of caution on the explantation of polyurethane breast implants.

PMID- 16641753
TI  - Giant blue urticaria following injection of patent blue dye for sentinel lymph
      node biopsy.

PMID- 16641754
TI  - Reconstruction of a large abdominal tissue defect with composite tissue using
      autologous dermis-vicryl-skin sandwich graft.

PMID- 16641755
TI  - Surgical reconstruction after liquid silicone injection for penile augmentation.

PMID- 16641756
TI  - Homolateral digital artery nerve graft.

PMID- 16641757
TI  - Retrograde perforator-based cross-leg fasciocutaneous flaps for distal leg and
      foot defects.

PMID- 16641758
TI  - Diffuse-type giant cell tumor.

PMID- 16641759
TI  - Amelioration of scars with the use of lipoinjection.

PMID- 16641760
TI  - Achievement of successful applicants to higher surgical training posts in plastic
      surgery in the United Kingdom.

PMID- 16641761
TI  - From the Bible to biosurgery: Lucilia sericata--plastic surgeon's assistant in
      the 21st century.

PMID- 16641762
TI  - Combination of rat vest, teeth shortening, and nail cutting to prevent
      autocannibalization and protect surgical flaps.

PMID- 16641763
TI  - Cadaver evaluation of EMG needle insertion techniques used to target muscles of
      the thorax.
AB  - STUDY DESIGN: Measure the accuracy of needle insertion in thoracic muscles of
      human cadavers. OBJECTIVES: Evaluate the effectiveness of known EMG techniques
      for sampling thoracic innervated muscles. SUMMARY OF BACKGROUND DATA: The
      evaluation of thoracic radiculopathies requires accurate electrodiagnostic
      techniques for evaluating the thoracic myotomes. METHODS: An American Board of
      Electrodiagnostic Medicine certified physician placed needles into pertinent
      muscles of the thorax and an anatomist serving as a blinded dissector recorded
      the path and accuracy of needle. RESULTS: Needle examination of thoracic muscles
      was as accurate as limb needle examination. No notable risks are noted in
      multifidus sampling. However, in the cadaver, some risks were noted in
      association with placements in the intercostal muscles. The target muscle was
      reliably sampled, but the rib or vertebral level was difficult to landmark in the
      cadaver. CONCLUSIONS: Needle examination of the thoracic multifidus and
      intercostals is reliable, although further confirmation is needed to accurately
      verify the appropriate vertebral or rib level being sampled.

PMID- 16641764
TI  - Anterior instrumentation of the cervicothoracic vertebrae: approach based on
      clinical and radiologic criteria.
AB  - STUDY DESIGN: Anterior instrumentation was performed in 42 cases of
      cervicothoracic tuberculosis operated using the modified anterior cervical
      approach. OBJECTIVES: To define the role of the modified anterior cervical
      approach in anterior reconstruction and instrumentation of the cervicothoracic
      vertebrae. To analyze the problems encountered during anterior stabilization in
      these patients. SUMMARY OF BACKGROUND DATA: In tuberculosis of cervicothoracic
      junction, direct anterior visualization is mandatory for optimal decompression of
      the spinal canal. Anterior reconstruction and stabilization has the advantage of
      providing immediate stability of vertebral column. The modified anterior cervical
      approach provides adequate exposure of the upper four thoracic vertebrae.
      However, radiologic and clinical criteria for anterior instrumentation of the
      cervicothoracic junction using the modified anterior cervical approach are
      unclear in literature. MATERIAL AND METHODS: A total of 42 patients with
      tuberculous kyphosis involving the cervicothoracic junction were operated. Based
      on the association of the sternal notch with the most distal normal vertebra, the
      patients were divided into 2 surgical groups. The long-neck patients were
      amenable to anterior instrumentation using the standard supraclavicular approach
      with a strap-muscle tenotomy. A manubriotomy was mandatory in short-neck patients
      for optimal visualization and proper placement of the implant. RESULTS AND
      CONCLUSION: Anterior reconstruction and instrumentation of the cervicothoracic
      junction offers a distinct advantage of a stable implant-bone construct
      anteriorly while preserving the posterior osseo-ligamentous tension band.
      Detailed preoperative assessment based on clinical and radiologic criteria helps
      in selection of patient for this procedure. Meticulous intraoperative technique
      helps to minimize the morbidity and complications associated with this procedure.

PMID- 16641765
TI  - Questionnaire survey of spine surgeons on the use of methylprednisolone for acute
      spinal cord injury.
AB  - STUDY DESIGN: A questionnaire survey. OBJECTIVE: Estimate the use and
      justification of the steroid protocol for spinal cord injury (SCI) patients.
      SUMMARY OF BACKGROUND DATA: There remains significant debate over clinical
      benefits and potential complications of the steroid protocol for SCI patients.
      METHODS: A survey was sent to spine surgeons requesting information on 1)
      specialization, 2) trauma center affiliation, 3) use of steroid protocol, 4)
      justification of using steroid protocol, and 5) SCI volume. RESULTS: Responses
      were received from 305 surgeons. Fourteen (4.6%) surgeons used steroids only if
      initiated before their consult, 262 (85.9%) would initiate if within the accepted
      8-hour timeframe, 20 (6.6%) did not use steroids at all, and 9 (3.0%) used a
      different protocol. Justification for steroids use: 65 improved recovery, 64
      institutional protocol, 110 medicolegal reasons, and 26 did not personally
      initiate steroids. Eighteen surgeons listed both clinical benefit and
      institutional protocol, and 22 others listed both institutional protocol and
      medicolegal reasons. CONCLUSIONS: The majority (90.5%) of responding surgeons
      used the steroid protocol; however, only 24.1% used the steroid protocol due to a
      belief in improved clinical outcomes.

PMID- 16641766
TI  - The McKenzie method for low back pain: a systematic review of the literature with
      a meta-analysis approach.
AB  - STUDY DESIGN AND OBJECTIVES: Meta-analysis of randomized controlled trials to
      evaluate the effectiveness of the McKenzie method for low back pain (LBP).
      SUMMARY OF BACKGROUND DATA: The McKenzie method is a popular classification-based
      treatment for LBP. The faulty equation of McKenzie to extension exercises
      (generic McKenzie) is common in randomized trials. METHODS: MEDLINE, EMBASE,
      PEDro, and LILACS were searched up to August 2003. Two independent reviewers
      extracted the data and assessed methodologic quality. Pooled effects were
      calculated among homogeneous trials using the random effects model. A sensitivity
      analysis excluded trials reporting on generic McKenzie. RESULTS: Eleven trials of
      mostly high quality were included. McKenzie reduced pain (weighted mean
      difference [WMD] on a 0- to 100-point scale, -4.16 points; 95% confidence
      interval, -7.12 to -1.20) and disability (WMD on a 0- to 100-point scale, -5.22
      points; 95% confidence interval, -8.28 to -2.16) at 1 week follow-up when
      compared with passive therapy for acute LBP. When McKenzie was compared with
      advice to stay active, a reduction in disability favored advice (WMD on a 0- to
      100-point scale, 3.85 points; 95% confidence interval, 0.30 to 7.39) at 12 weeks
      of follow-up. Heterogeneity prevented pooling of studies on chronic LBP as well
      as pooling of studies included in the sensitivity analysis. CONCLUSIONS: There is
      some evidence that the McKenzie method is more effective than passive therapy for
      acute LBP; however, the magnitude of the difference suggests the absence of
      clinically worthwhile effects. There is limited evidence for the use of McKenzie
      method in chronic LBP. The effectiveness of classification-based McKenzie is yet
      to be established.

PMID- 16641767
TI  - Safety and efficacy of C2 pedicle screws placed with anatomic and lateral C-arm
      guidance.
AB  - STUDY DESIGN: This is a retrospective review of 150 C2 pedicle screw placements.
      Candidates had their C2 pedicle morphology assessed through three-dimensional
      imaging, including preoperative image guidance. After surgery, the patients were
      serially CT scanned. Follow-up, with fusion assessment, ranged from 1 to 12
      years. OBJECTIVE: We will show that an open technique combined with lateral C-arm
      guidance provides rapid placement of C2 pedicle screws. SUMMARY OF BACKGROUND
      DATA: C2 pedicle screws can be successful anchors for a variety of cervical
      problems. Standard intraoperative image guidance, biplane fluoroscopy, or free
      hand techniques all have their drawbacks. METHODS: After adequate C2 exposure,
      the C2 pedicle is palpated. The dissector remains stationary to provide coronal
      orientation while a lateral C-arm radiograph is obtained for sagittal
      orientation. The drill trajectory is set, the C2 pedicle cannulated, and a
      cancellous screw placed. RESULTS: A total of 71 patients had bilateral screws
      placed and 8 patients had unilateral screws placed. The overall complication rate
      was 2.7%. CONCLUSIONS: In our series, we have found a consistent way to cannulate
      the C2 pedicle. C2 fixation serves as an integral part of cervical
      reconstruction. Preoperative planning, anatomic knowledge, and lateral C-arm
      orientation create a low morbidity method for C2 screw placement.

PMID- 16641768
TI  - Delayed hypopharyngeal and esophageal perforation after anterior spinal fusion:
      primary repair reinforced by pedicled pectoralis major flap.
AB  - STUDY DESIGN: This report documents a case of delayed hypopharyngeal and
      esophageal perforation after anterior spinal fusion and reviews relevant
      literature. OBJECTIVES: Presentation of an alternative solution of primary repair
      and reinforcement of a delayed esophageal and hypopharyngeal perforation after
      anterior spinal fusion. SUMMARY OF BACKGROUND DATA: Anterior plating is generally
      used for stabilization after cervical spine trauma. Esophageal and hypopharyngeal
      perforation is a rare but potentially life-threatening complication due to
      mediastinitis with consecutive septic shock and multiorgan failure. METHODS: Our
      patient was operated on after cervical trauma caused by car accident. The
      neurologic condition did not improve in the postoperative period. About 4 months
      later, the patient had increasing dysphagia as well as episodes of odynophagia.
      Flexible esophagoscopy showed a perforation of a part of the plate from the
      hypopharynx down to the proximal esophagus. Primary repair reinforced by a
      pedicled pectoralis major flap was done without complications. RESULTS:
      Postoperative fluoroscopy as well as endoscopy showed no signs of perforation.
      Swallowing was possible without any further episodes of dysphagia or odynophagia.
      Neck movement was unconfined. CONCLUSIONS: Primary repair reinforced by pedicled
      pectoralis major flap has been shown to be an alternative in case of combined
      hypopharyngeal and esophageal perforation due to orthopedic spine stabilization.
      Advantage of the pectoralis major muscle flap is no functional loss of neck
      movement.

PMID- 16641770
TI  - Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of
      porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads.
AB  - STUDY DESIGN: In vitro assessment of the effects of platelet-rich plasma on the
      extracellular matrix metabolism of porcine intervertebral disc cells. OBJECTIVES:
      To determine whether platelet-rich plasma is effective in stimulating cell
      proliferation and extracellular matrix metabolism by porcine disc cells cultured
      in alginate beads. SUMMARY OF BACKGROUND DATA: Platelet-rich plasma is used to
      accelerate wound healing and tissue regeneration. Activated platelets release
      multiple growth factors that regulate cell proliferation, differentiation, and
      morphogenesis. Individual growth factors present in platelet-rich plasma have
      been demonstrated to affect the metabolism of intervertebral disc cells. METHODS:
      Platelet-poor and platelet-rich plasma was isolated from fresh porcine blood
      using a commercially available platelet concentration system. After preculture
      for 7 days and serum starvation for 24 hours, the beads containing nucleus
      pulposus and anulus fibrosus cells were then cultured for another 72 hours in
      serum-free medium, 10% fetal bovine serum, 10% platelet-poor plasma, or 10%
      platelet-rich plasma. The synthesis of proteoglycans and collagen, the
      accumulation of proteoglycans, and the DNA content were biochemically assessed.
      RESULTS: Platelet-rich plasma had a mild stimulatory effect on cell proliferation
      of intervertebral disc cells. Platelet-rich plasma treatment significantly
      upregulated proteoglycan and collagen synthesis and proteoglycan accumulation
      when compared with platelet-poor plasma. CONCLUSIONS: Platelet-rich plasma was
      effective in stimulating cell proliferation and extracellular matrix metabolism.
      The response to platelet-rich plasma was greater in the case of anulus fibrosus
      cells than of nucleuspulposus cells. The local administration of platelet-rich
      plasma might stimulate intervertebral disc repair. In addition, given the risks
      of using animal serum for tissue engineering, autologous blood may gain favor as
      a source of growth factors and serum supplements needed for stimulating cells to
      engineer intervertebral disc tissues.

PMID- 16641771
TI  - A biomechanical assessment of infra-laminar hooks as an alternative to supra
      laminar hooks in thoracolumbar fixation.
AB  - STUDY DESIGN: Biomechanical study, using human cadaveric spines, of two types of
      posterior fixation in the thoracolumbar spine. OBJECTIVES: To compare fixation in
      the thoracolumbar spine using pedicle screws combined with infra-laminar hooks
      (at both the cranial and caudal ends of the same vertebra) with fixation using
      pedicle screws alone. SUMMARY OF BACKGROUND DATA: The standard method of using
      laminar hooks is to place supra-laminar hooks at the level above the vertebra
      being fixed by the cranial pedicle screws, and infra-laminar hooks at the level
      of the vertebra receiving the caudal pedicle screws. However, using this method,
      a single normal motion segment is killed. In the proposed technique, infra
      laminar hooks will be used at the same level as the cranial pedicle screws, thus
      sparing the superior adjacent segment. METHODS: PEDICLE SCREW LOOSENING TEST:
      Nine vertebrae (T9-L2) had pedicle screws inserted into both pedicles. On one
      side, the pedicle screw was connected to a fixation rod, while on the other side
      the pedicle screw was combined with an infra-laminar hook and connected to a rod.
      The rod on one side was then pushed with increasing force until loosening of the
      screw. The same test was repeated on the other rod until loosening of the screw.
      The reverse test (i.e., pulling until loosening) was done in a similar manner on
      another nine vertebrae. BIOMECHANICAL STIFFNESS TEST: Eight spines (T12-L2) were
      biomechanically tested in: axial compression, flexion, extension, left and right
      lateral bending, and left and right axial torsion. This sequence was applied to:
      1) the intact spine; 2) after applying pedicle screws and infra-laminar hooks
      with rods to the destabilized spine; and 3) after removal of the hooks (with the
      pedicle screw and rods still inserted). From the load-deformation curves
      obtained, stiffness values were calculated. RESULTS: PEDICLE SCREW LOOSENING
      TEST: The pedicle screw loosening tests showed that a pedicle screw combined with
      an infra-laminar hook offers significantly greater fixation strength as compared
      to a pedicle screw alone. Biomechanical stiffness test. Fixation by pedicle
      screws combined with infra-laminar hooks, placed on the vertebra fixed by pedicle
      screws at both the cranial and caudal ends, offered a stiffer construct as
      compared to fixation by pedicle screws alone. CONCLUSIONS: This method offers a
      firm construct without sacrificing a normal motion segment.

PMID- 16641772
TI  - Multilevel cervical fusion and its effect on disc degeneration and osteophyte
      formation.
AB  - STUDY DESIGN: The effect of single and double cervical fusion on adjacent
      segments was investigated using a finite element model of the cervical spine. A
      healthy spine and a cervical spine with a single and double fusion at different
      levels were analyzed and evaluated. Disc degeneration and osteophyte formation at
      the endplates and joints can then be addressed. OBJECTIVES: To evaluate the
      biomechanical effects of cervical fusion on the cervical spine from C3-C7. The
      goal was to asses the increase of intervertebral disc and bone stress induced by
      cervical fusion, the effects of single versus double level fusion, and whether
      the level in which the fusion is performed, might affect the biomechanics of the
      spine. SUMMARY OF BACKGROUND DATA: Clinical studies have reported that 25% of
      fusion patients report further degenerative problems within 10 years of fusion.
      METHODS.: Four finite element models of single fusion at different levels were
      generated, as well as three additional models for the case of double fusion. The
      maximum von Mises stresses for anulus, nucleus, and endplates and the motion of
      the nonfused segments were obtained during lateral bending, flexion, axial
      torsion, and extension. Each case was compared with the normal cervical spine.
      RESULTS: Results showed stress increases of up to 96% in the anulus, nucleus, and
      endplates after fusion. Facet constraining prevents increases in stress during
      extension. The stresses at all levels tend to be larger for double than for
      single fusion. CONCLUSIONS: The results of this study quantify the significant
      increase in the level of stresses below and above the fused segments in the
      cervical spine. A sustained level of this stress can lead to further discs
      degeneration and osteophytes.

PMID- 16641773
TI  - Os odontoideum revisited: the case for a multifactorial etiology.
AB  - STUDY DESIGN: Retrospective analysis of our experience with os odontoideum at the
      Children's Hospital of Philadelphia. OBJECTIVE: To review the origin of os
      odontoideum and provide evidence for two separate etiologies. SUMMARY OF
      BACKGROUND DATA: The etiology of os odontoideum has been debated in the
      literature. Most authors support a post-traumatic etiology; however, some
      evidence exists to support a congenital origin. METHODS: We reviewed all 519
      abnormal cervical spine radiographs performed from 1991 to 2004 to identify os
      odontoideum. Medical records and imaging studies were examined to determine:
      history of trauma, severity of injury, interval from injury to presentation,
      coexisting syndromes, and associated congenital cervical spine anomalies.
      RESULTS: Sixteen of 519 patients (3.1%) had os odontoideum. Only 8 of 16 patients
      reported previous trauma. Only 3 of these 8 injuries occurred with an interval
      remote enough to allow remodeling of the dens to an ossicle by the time of
      presentation. Six of 16 patients had associated congenital anomalies in the
      cervical spine. Three of 16 had a coexisting genetic syndrome. CONCLUSION: Our
      data supports two separate etiologies for the os odontoideum: post-traumatic and
      congenital. The data should raise awareness that some children with preexisting
      syndromes may develop os odontoideum without previous trauma.

PMID- 16641774
TI  - Outcome of local bone versus autogenous iliac crest bone graft in the
      instrumented posterolateral fusion of the lumbar spine.
AB  - STUDY DESIGN: Retrospective, comparative study of clinical and radiologic outcome
      with independent, blinded observer. OBJECTIVES: To compare the clinical and
      radiologic outcome of instrumented posterolateral lumbar fusion using local bone
      versus autogenous iliac crest bone graft (ICBG). SUMMARY OF BACKGROUND DATA:
      There is no published report of outcome of posterolateral spinal fusion using
      local bone alone for degenerative disorders of the lumbar spine. MATERIALS AND
      METHODS: Seventy-six cases (male 26, female 50) of spinal stenosis, operated
      during 1996 and 1997 by the senior author, were reviewed. All the cases had
      decompression and posterior spinal fusion with pedicle screw instrumentation.
      Forty cases had only local bone graft obtained from decompression, morselized in
      a bone mill, and 36 cases had autogenous ICBG. Mean age was 60 years (range, 27
      83 years). Fusion was performed at one level in 51 (67%), two levels in 16 (21%),
      three levels in 5 (7%), and four or more levels in 4 cases (5%). Minimum follow
      up was 2-years (mean, 28 years; range, 24-72 months). An independent, blinded
      radiologist rated plain radiographs as fused, indeterminate, or nonunion.
      RESULTS: There was no difference in age, sex, and diagnosis between the two
      groups. Overall fusion rate was higher in the ICBG group (75%, 27 of 36) compared
      with the local bone group (65%, 26 of 40) but not significantly different (P =
      0.391). Analyzed separately according to the number of fusion levels, the local
      bone group achieved similar fusion rate ( approximately 80%) in single-level
      fusion but a much smaller fusion rate in multilevel fusion (20% vs. 66%, P =
      0.029) compared with the ICBG group. Mean improvement in the Oswestry Disability
      Inventory was 36% in the local bone group and 32% in the ICBG group. There was no
      significant difference in overall clinical outcome between the two groups. There
      was no correlation between fusion status and clinical outcome. Blood loss and
      hospital stay were significantly less in the local bone group; however, blood
      losswas more significantly related to the sum total number of segments undergoing
      decompression and fusion. CONCLUSIONS: Use of local bone graft alone achieved a
      similar fusion rate in single-level fusion but a much smaller fusion rate in
      multilevel fusion compared with the ICBG group. Local bone graft alone achieved a
      similar clinical outcome but less morbidity irrespective of number of fusion
      level.

PMID- 16641775
TI  - Lumbar total disc arthroplasty utilizing the ProDisc prosthesis in smokers versus
      nonsmokers: a prospective study with 2-year minimum follow-up.
AB  - STUDY DESIGN: Prospective nonrandomized clinical series. OBJECTIVES: To evaluate
      the efficacy of ProDisc lumbar artificial disc replacement (ADR) in smokers
      versus nonsmokers. SUMMARY OF BACKGROUND DATA: Smoking is a negative predictor in
      fusion surgery. To date, a prospective study of the treatment of incapacitating
      discogenic low back pain using ADR in smokers versus nonsmokers has not been
      described. METHODS: A prospective analysis was performed on 104 patients with
      disabling discogenic low back pain treated with single-level lumbar ProDisc total
      disc arthroplasty. Smokers and nonsmokers were assessed before surgery and after
      surgery using patient satisfaction, Oswestry, and Visual Analog Scores.
      Additionally, preoperative and postoperative neurologic, radiographic, and pain
      medication assessments were performed at similar postoperative intervals.
      RESULTS: Oswestry, Visual Analog Scores, and patient satisfaction scores revealed
      statistical improvement beginning 3 months after surgery and were maintained at
      minimum 2-year follow-up. Patient satisfaction scores were higher in smokers
      (94%) than in nonsmokers (87%) at 2-year follow-up (P = 0.07). Radiographic
      analysis revealed an affected disc height increase from 4 mm to 13 mm (P < 0.05)
      and an affected disc motion from 3 degrees to 7 degrees (P < 0.05). No cases of
      loosening, dislodgment, mechanical failure, infection, or fusion of the affected
      segment occurred. CONCLUSIONS: The results of our study indicate that smokers do
      equally well compared with nonsmokers when ProDisc ADR is used in the treatment
      of debilitating lumbar spondylosis. Patient outcome and radiographic scores
      showed significant improvement compared with preoperative levels. Although not
      evident in our series, additional surveillance for intraoperative and
      postoperative vascular spasm and occlusion may be warranted in smokers.

PMID- 16641776
TI  - A Cochrane review of superficial heat or cold for low back pain.
AB  - STUDY DESIGN: Cochrane systematic review. OBJECTIVE: To assess the effects of
      superficial heat and cold therapy for low back pain in adults. SUMMARY OF
      BACKGROUND DATA: Heat and cold are commonly used in the treatment of low back
      pain. METHODS: We searched electronic databases from inception to October 2005.
      Two authors independently assessed inclusion, methodologic quality, and extracted
      data, using the criteria recommended by the Cochrane Back Review Group. RESULTS:
      Nine trials involving 1,117 participants were included. In two trials of 258
      participants with a mix of acute and subacute low back pain, heat wrap therapy
      significantly reduced pain after 5 days (weighted mean difference [WMD], 1.06;
      95% confidence interval [CI], 0.68-1.45, scale range, 0-5) compared with oral
      placebo. One trial of 90 participants with acute low back pain found that a
      heated blanket significantly decreased pain immediately after application (WMD, 
      32.20; 95% CI, -38.69 to -25.71; scale range, 0-100). One trial of 100
      participants with a mix of acute and subacute low back pain examined the
      additional effects of adding exercise to heat wrap and found that it reduced pain
      after 7 days. CONCLUSIONS: The evidence base to support the common practice of
      superficial heat and cold for low back pain is limited, and there is a need for
      future higher-quality randomized controlled trials. There is moderate evidence in
      a small number of trials that heat wrap therapy provides a small short-term
      reduction in pain and disability in a population with a mix of acute and subacute
      low back pain, and that the addition of exercise further reduces pain and
      improves function. There is insufficient evidence to evaluate the effects of cold
      for low back pain and conflicting evidence for any differences between heat and
      cold for low back pain.

PMID- 16641777
TI  - Kyphectomy in children with myelodysplasia: results 1994-2004.
AB  - STUDY DESIGN: We retrospectively studied 24 consecutive pediatric patients with
      lumbar kyphosis due to myelodysplasia who had received corrective surgical
      treatment with the Warner and Fackler technique from 1994 to 2004. OBJECTIVES:
      The purpose of the study was to evaluate the technical problems and outcome and
      to identify complications of this treatment modality, especially regarding the
      biomechanics. SUMMARY OF BACKGROUND DATA: The management of lumbar kyphosis (8%
      20%) in conjunction with myelodysplasia is difficult. In 1993, Warner and Fackler
      presented an elegant surgical technique, which was used here. METHODS: Corrective
      surgery was performed in 24 patients with an average preoperative lumbar kyphosis
      of 124 degrees . The correction was achieved by kyphectomy combined with
      stabilization using rods and wires as described by Warner and Fackler. Outcome
      was rated and complications were identified using data from the clinical records.
      For biomechanical analysis of the surgical construct, a force model was
      developed. RESULTS: The mean extent of lumbar kyphosis could be corrected from
      124 degrees before surgery to 43 degrees after surgery. Biomechanical analysis
      showed that inadequate correction results in implant failure. CONCLUSION: Surgery
      should always be performed with the intention to reestablish the sagittal profile
      inasfar as possible so as to reduce the risk of implant failure.

PMID- 16641778
TI  - Anterior surgery with insertion of titanium mesh cage and posterior instrumented
      fusion performed sequentially on the same day under one anesthesia for septic
      spondylitis of thoracolumbar spine: is the use of titanium mesh cages safe?
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the outcome on patients
      with pyogenic spondylitis of the thoracolumbar spine following combined anterior
      and posterior surgery. SUMMARY AND BACKGROUND DATA: Several methods of surgical
      treatment of pyogenic spondylitis have been reported. These include anterior
      approach, staged and simultaneous anterior decompression, and posterior
      stabilization. The use of anterior implants in the presence of an infection
      presents a challenge for spine surgeons. This study analyzes the clinical and
      radiologic outcome of surgical intervention on patients with pyogenic spondylitis
      of the thoracolumbar spine who were treated surgically for intractable pain,
      instability, and neurologic impairment. METHODS: Fourteen patients (6 women, 8
      men) with thoracolumbar spondylitis were treated with anterior surgery with
      insertion of titanium mesh cage and posterior instrumented fusion performed
      sequentially on the same day under one anesthesia. The age (average, SD) of the
      patients at the time of surgery was 55 +/- 16 years (range, 29-83 years). Most
      patients had also systemic diseases as lung tuberculosis, hepatic cirrhosis,
      diabetes mellitus, or chronic renal failure. Patients were evaluated before and
      after surgery in terms of pain, neurologic level, sagittal spinal balance, and
      radiologic fusion. RESULTS: The average duration of the combined surgery was 4.5
      hours. All patients were observed up for an average of 45 months (range, 37-116
      months). The Visual Analog Scale score (average, range) improved from 7 (range, 4
      10) before surgery to 2 (range, 0-5) after surgery. Correction (average, range)
      of segmental kyphotic deformity was 6 degrees (range, 0 degrees-11 degrees)
      without loss of correction at the final observation. Neither a postoperative
      change of the position of mesh cage nor any posterior instrumentation failure was
      recorded. Patients with incomplete neurologic impairment showed improvement after
      surgery at an average 1.4 Frankel's grade. There was one complication, an
      anterior wound abscess culminating in an abdominal hernia. CONCLUSIONS: This
      clinical study showed that patients with thoracolumbar osteomyelitis can
      successfully undergo anterior surgery with insertion of titanium mesh cage and
      posterior instrumented fusion performed sequentially on the same day under one
      anesthesia. The presence of the mesh cage anteriorly at the site of spondylitis
      had no negative influence on the course of infection healing, and additionally it
      stabilized the affected segment maintaining sufficient sagittal profile.

PMID- 16641779
TI  - Usefulness of white blood cell differential for early diagnosis of surgical wound
      infection following spinal instrumentation surgery.
AB  - STUDY DESIGN: The white blood cell (WBC) count and WBC differential were measured
      prospectively in patients after spinal instrumentation surgery with or without
      surgical wound infection. OBJECTIVES.: To investigate the usefulness of WBC
      differential for early diagnosis of surgical wound infection after spinal
      instrumentation surgery. SUMMARY OF BACKGROUND DATA: Renewed elevation of C
      reactive protein (CRP) or WBC, gallium scan, and CRP/transthyretin mass
      concentration ratio were reported for early diagnosis of surgical wound
      infection. METHODS: A total of 39 patients were enrolled in this study: 13
      patients who developed wound infection within 2 weeks after spinal
      instrumentation surgery (infection group) and 26 patients who were comparable
      with those patients included in the infection group with regard to age, sex, and
      surgical techniques used (control group). The WBC count and WBC differential were
      determined before and after surgery. RESULTS: In both groups, WBC and percentage
      and number of neutrophils showed nearly same change until postoperative 4 days
      (day 4). However, in the infection group, these parameters had increased after
      day 4. In both groups, the percentage and number of lymphocytes decreased to 10%
      or less and 1,000/microL or less on day 1, respectively. These lymphocyte
      parameters began to gradually normalize on day 4 and returned to the preoperative
      level 3 weeks after surgery in the control group. On the other hand, these
      parameters remained 10% or less and 1,000/muL or less until day 11 in the
      infection group. In patients with infection, the percentage and number of
      lymphocytes significantly decreased as early as on day 4. CONCLUSION: Lymphopenia
      represents immunodepression status, thus indicating the increased susceptibility
      to infection, which may lead to the development of postoperative infection. If
      lymphopenia is diagnosed as early as possible, surgical wound infection can be
      treated promptly without removing the instruments.

PMID- 16641780
TI  - Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve
      fibers in vertebral endplates of patients with discogenic low back Pain and Modic
      Type 1 or Type 2 changes on MRI.
AB  - STUDY DESIGN: Immunohistochemistry for tumor necrosis factor (TNF) and protein
      gene product (PGP) 9.5 in vertebral endplates of patients with discogenic low
      back pain and Modic Type 1 or Type 2 endplate changes on MRI. OBJECTIVES: To
      examine whether inflammatory cytokines and nerve in-growth into the vertebral
      endplate are associated with discogenic low back pain. SUMMARY AND BACKGROUND
      DATA: Degenerated discs and endplate abnormalities can be a cause of discogenic
      low back pain. However, the presence of TNF-immunoreactive cells and PGP 9.5
      immunoreactive nerve fibers has not been studied in patients with discogenic low
      back pain and endplate changes on MRI. METHODS: Eighteen endplates showing either
      normal intensity signals on MRI (endplate change -), Modic Type 1 signals (low
      intensity on T1-weighted spin-echo images), or Modic Type 2 signals (high
      intensity) from patients with discogenic low back pain (n = 14) or controls
      requiring surgery for other back problems (n = 4; scoliosis and traumatic injury
      of vertebra) were harvested during surgery. Endplates were immunostained using
      antibodies to TNF and PGP 9.5 and immunostained cells and nerve fibers in the
      endplates were counted. RESULTS: Vertebral endplates from patients with Modic
      Type 1 or Type 2 endplate changes on MRI had significantly more PGP 9.5
      immunoreactive nerve fibers and TNF-immunoreactive cells in comparison with
      patients with normal endplates on MRI (P < 0.01). The number of TNF
      immunoreactive cells in endplates exhibiting Modic Type 1 changes was
      significantly higher than in endplates exhibiting Modic Type 2 changes (P <
      0.05). CONCLUSIONS: The results suggest that endplate abnormalities are related
      to inflammation and axon growth induced by TNF. TNF expression and PGP 9.5
      positive nerve in-growth in abnormal endplates may be a cause of low back pain.

PMID- 16641781
TI  - Serum lipids and low back pain: an association? A follow-up study of a working
      population sample.
AB  - STUDY DESIGN: Cohort study with 5-, 10-, and 28-year follow-up. OBJECTIVES: To
      examine associations between baseline serum lipid concentrations and later low
      back pain (LBP). SUMMARY OF BACKGROUND DATA: Atherosclerosis of the lumbar
      vessels has been suggested as a mechanism leading to disc degeneration and LBP.
      Cholesterol is considered essential for atherosclerosis development. METHODS: A
      sample (n = 902) of employees in an engineering company was examined for serum
      total cholesterol and triglycerides, body mass index (BMI), smoking, exercise,
      work history, and LBP in 1973. By November 2000, 232 subjects had died. In 1978,
      748 (84% of the survivors), in 1983, 654 (76%), and in 2000, 546 (81%) responded
      to a follow-up questionnaire. RESULTS: In men, baseline serum total cholesterol
      predicted new cases of radiating LBP in the 5-year follow-up (highest tertile vs.
      lowest: odds ratio [OR], 2.5; 95% confidence interval [CI], 1.1-5.9) and in the
      10-year follow-up (OR, 2.8; 95% CI, 1.3-6.1), adjusted for age, occupational
      class, work history, BMI, smoking and exercise. Also, serum triglycerides
      predicted new cases in the latter examination (OR, 2.6; 95% CI, 1.2-5.8). In
      women, no associations were seen until the 10-year follow-up, when their results
      were similar to those in men. In the total material, serum total cholesterol
      predicted radiating LBP reported both at the 10- and the 28-year follow-up.
      CONCLUSIONS: High serum lipids predicted incident radiating LBP, consistent with
      the atherosclerosis-LBP hypothesis.

PMID- 16641782
TI  - Clinical course and impact of fear-avoidance beliefs in low back pain:
      prospective cohort study of acute and chronic low back pain: II.
AB  - STUDY DESIGN: Prospective inception cohort study. OBJECTIVES: To compare the
      clinical course of fear-avoidance beliefs in acute and chronic low back pain
      (LBP) and investigate the contribution of fear-avoidance beliefs to predict pain
      and disability after 1 year. SUMMARY OF BACKGROUND DATA: Fear-avoidance beliefs
      are involved in disability development. There is little knowledge on the
      development of fear-avoidance beliefs among different LBP subgroups. METHODS:
      Patients with acute (n = 123) and chronic (n = 50) LBP completed a comprehensive
      assessment, including the Fear-Avoidance Beliefs Questionnaire (FABQ), and were
      followed at 3, 6, 9, and 12 months. RESULTS: At baseline, patients with chronic
      LBP had significantly higher FABQ-scores for work (FABQ-Work) than patients with
      acute LBP (P < 0.001), and this difference remained unchanged over 1 year (P >
      0.21). At baseline, there was no statistical significant difference in FABQ
      scores for physical activity (FABQ-PA) between the two groups (P = 0.57). FABQ-PA
      scores decreased significantly over the first 4 weeks among patients with acute
      LBP during follow-up and remained unchanged thereafter, whereas in the chronic
      sample the FABQ-PA scores were unchanged throughout the first year (time effect,
      P < 0.001; and interaction effect, P < 0.001). In the acute sample, FABQ-Work
      predicted pain (P < 0.05) and disability at 12 months (P = 0.01). In the chronic
      sample, FABQ-PA predicted disability at 12 months (P = 0.03). The associations
      between the FABQ and pain/disability disappeared with distress included in the
      models. CONCLUSION: Patients with chronic LBP had more fear-avoidance beliefs for
      work than patients with acute LBP. There were small changes in fear-avoidance
      beliefs during the year of follow-up, except for a rapid decrease during the
      first month in the FABQ-PA in the acute sample. Fear-avoidance beliefs predicted
      pain and disability at 12 months after adjusting for socio-demographic and pain
      variables. Distress was a stronger predictor than fear-avoidance beliefs.

PMID- 16641783
TI  - Radiographic measurement techniques for sacral fractures consensus statement of
      the Spine Trauma Study Group.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: Members of the Spine Trauma Study
      Group evaluated various imaging methods and compiled standardized approaches to
      making radiographic measurements for the assessment of sacral fractures. SUMMARY
      OF BACKGROUND DATA: The diagnosis of sacral fractures is frequently missed or
      delayed, and the treatment is controversial, with significant variations in
      recommendations regarding nonoperative treatment, neural decompression, and
      internal fixation. A paucity of specific radiographic measurements and criteria
      exist to aid the clinician in making sound treatment decisions. This may obligate
      surgeons to base clinical decisions on nonstandardized, nonvalidated
      recommendations and measures and, in some cases, anecdotal evidence. We think
      that a critical first step toward valid and optimal clinical decision-making
      requires an accurate and clear definition of imaging measurement parameters used
      to evaluate sacral injuries and gather data for future studies. METHODS: A review
      of the English-speaking literature was performed to assess cited radiographic
      measurement techniques of sacral fractures currently in use. This allowed the
      formulation of detailed radiographic assessments designed to more reliably
      describe sacral fracture morphometry. RESULTS: These measurements include:
      anterior-posterior sacral fracture displacement (axial computed tomography [CT]
      of the pelvis), vertical sacral fracture displacement (coronal CT
      reconstruction), anterior-posterior translation and kyphotic angulation (sagittal
      CT reconstructions), and degree of central canal involvement and foraminal
      encroachment (axial CT with fine cuts and coronal and sagittal reconstructions).
      Other radiographic factors that should be considered that may impact treatment
      outcomes include the level and type of sacral fracture, lumbosacral junction and
      sacroiliac joint involvement, and associated pelvic ring injury. CONCLUSIONS:
      With adoption of these radiographic guidelines, future studies will have a
      uniform method in which to describe sacral injuries and therefore allow study of
      the efficacy of various recommended treatment protocols.

PMID- 16641784
TI  - Cord and cauda equina injury complicating elective orthopedic surgery.
AB  - STUDY DESIGN: Presented is a case series of 3 patients, all of whom developed
      neurologic deficits due to cord or cauda equina compression during elective
      extremity surgery. OBJECTIVES: To identify characteristics of presentation that
      may differentiate cord or cauda equina injury from peripheral nerve palsy
      following extremity surgery and to establish the value of early decompression in
      patients with intraoperative injury. SUMMARY OF BACKGROUND DATA: Intraoperative
      neural injury has been described in association with epidural and spinal
      anesthesia, with cervical or spinal manipulation in the face of instability, and
      with ischemic injury suffered during extensive vascular repair. However, it has
      not been described after uncomplicated elective extremity surgery. METHODS:
      Retrospective review of a case series. RESULTS: In 1 patient, intraoperative
      paraplegia occurred after routine shoulder arthroscopy. A second patient
      underwent elective bilateral total hip replacement and awoke with neurologic
      deficits in both lower extremities, then went on to develop an acute cauda equina
      syndrome. The third patient developed a central cord syndrome following an
      otherwise uncomplicated total hip replacement. Two patients were initially
      misdiagnosed as peripheral nerve palsies. All 3 patients had preexisting spinal
      stenosis at the level of neural injury. All underwent routine positioning and
      anesthetic care but were recognized as having a neural injury early in the
      recovery period. In only 1 case was the diagnosis of a cord level injury made
      immediately. All 3 patients were treated with urgent surgical decompression once
      diagnosed. Following surgery, neurologic symptoms improved in each of the 3
      patients allowing early mobilization. CONCLUSIONS: Spontaneous neural injury is
      rare but can occur to the anesthetized patient. Neurologic examination should be
      routinely performed in the recovery room; and if significant neurologic deficits
      are seen, investigative workup should not be delayed. If an intraspinal lesion is
      identified, immediate decompression may offer favorable results. Neurologic
      deficits should not be dismissed as peripheral palsies without careful
      evaluation.

PMID- 16641785
TI  - Vladimir Janda, MD, DSc: tribute to a master of rehabilitation.
AB  - The purpose of this presentation is to pay tribute to the life's work of
      Professor Vladimir Janda, a key figure in the 20th Century rehabilitation
      movement. An accomplished neurologist, he founded the rehabilitation department
      at Charles University Hospital in Prague, Czechoslovakia. He was one of the
      seminal members of the Prague school of manual medicine and rehabilitation that
      expanded its influence throughout Central and Eastern Europe. His observations
      regarding muscle imbalances, faulty posture and gait, and their association with
      chronic pain syndromes, etiologically, diagnostically, and therapeutically,
      influenced the rehabilitation world. The authors comprise a multinational,
      multiprofessional group representative of rehabilitation specialists around the
      world who would like to pay tribute and give a final word of thanks to this
      innovative educator, clinician, and author.

PMID- 16641788
TI  - Microbubble contrast for radiological imaging: 1. Principles.
AB  - Microbubble contrast for ultrasound imaging in radiology has finally come of age,
      adding entirely new capabilities to real time imaging. Following a bolus
      injection into a peripheral vein of as little as 0.1mL of an aqueous suspension,
      contrast specific imaging modes show parenchymal and lesional perfusion in real
      time in the major organs of the abdomen and pelvis as well as breast, thyroid and
      prostate. These new imaging modes exploit the unique interaction between
      ultrasound and microbubbles, which gives rise to nonlinear echoes that are
      readily distinguishable from those of tissue. Furthermore, microbubbles can be
      deliberately disrupted by the ultrasound imaging field. The rate at which fresh
      bubbles then replenish the scanplane can be metered in subsequent images,
      offering a means to quantify both flowrate and relative vascular volume of the
      microvasculature in both organs and solid lesions.

PMID- 16641789
TI  - Microbubble contrast for radiological imaging: 2. Applications.
AB  - Conventional Doppler provides information on blood flow including both flow and
      direction and flow velocity. Information on the slowly flowing blood at the
      capillary level, however, has not previously been available on state of the art
      Doppler. Contrast enhanced ultrasound provides, for the first time, information
      on tissue perfusion such that CEUS may now play a role in liver mass
      characterization and the evaluation of masses in other solid viscera similar to
      the role of contrast enhanced CT and MR scan. Renal applications include similar
      mass characterization and evaluation of renal perfusion and the renal
      vasculature. Surveillance of aortic stent grafts, monitoring RFA, and evaluation
      of both prostate and breast masses are further areas of interest. Our experience
      with ultrasound contrast expands progressively, and essentially adds vascular
      information to any region when blood flow information is required. The addition
      of CEUS to clinical practice has significant impact on patient management. In
      patients with an incidental liver mass on sonography, for example,
      characterization at the time of tis detection reduces the time to diagnosis and
      decreases referrals to CT or MR scan. Ultrasound contrast agents are easy to use,
      have a very low incidence of adverse events, and are unaffected by renal
      function. As they add no radiation for their use, they are highly appropriate in
      pediatric and young adult patients. Ultrasound is enhanced by addition of
      contrast agents.

PMID- 16641790
TI  - Imaging of malignant liver masses: characterization and detection.
AB  - Noninvasive characterization of focal liver lesions is largely based on their
      enhancement patterns on contrast-enhanced imaging. The use of microbubble
      contrast agents combined with specialized ultrasound (US) techniques has
      significantly expanded the role of US in the diagnosis of focal liver lesions
      based on their vascularity and specific enhancement features. With the advantage
      of real-time scanning, contrast-enhanced ultrasound (CEUS) can evaluate small
      lesions that are indeterminate on computed tomography (CT) or magnetic resonance
      imaging (MR), because CEUS is far less affected by timing issues. Hepatocellular
      carcinoma is typically characterized by increased arterial flow with frequent
      dysmorphic tumor vessels and decreased portal venous flow. However, negative
      enhancement in the portal phase is often not obvious until late (>2 minutes). On
      the other hand, metastasis shows prompt brief arterial hypervascularity, with
      either a rim or diffuse pattern and rapid washout, seen as perfusion defects
      during the portal venous phase. This pattern of complete rapid washout of
      metastases within the homogeneously enhanced background liver parenchyma can
      improve their detection and also improve differentiation from hepatocellular
      carcinoma or benign focal lesions. All malignant lesions generally show negative
      enhancement or washout during the extended portal venous phase, and this pattern
      is useful to differentiate them from benign lesions. Microbubble agents, confined
      to the intravascular space, may infrequently characterize malignancy by showing
      washout whereas CT or MR shows persistent enhancement due to interstitial
      distribution.

PMID- 16641791
TI  - Benign liver masses: imaging with microbubble contrast agents.
AB  - Benign focal liver lesions are frequently encountered in routine ultrasound (US)
      scanning as well as in staging US examination for the patients with known
      malignancy. Noninvasive characterization of benign liver masses by imaging
      features has been a challenge for the radiologist. Some benign liver masses show
      typical findings on US; however, these findings are not highly specific. Contrast
      enhanced ultrasound (CEUS) is useful to make an instant, confident diagnosis of
      benign liver masses. Contrast-enhanced multiphasic computed tomography (CT) is an
      excellent imaging technique to detect and characterize focal liver masses. But
      there are a considerable number of indeterminate focal liver lesions, which
      require further evaluation. CEUS provides the evaluation of perfusion and
      hemodynamics of nodular liver lesions as well as real-time morphologic evaluation
      of lesion vascularity. Most benign liver masses show characteristic features on
      CEUS, allowing an accurate diagnosis. This review article describes typical
      enhancement features of common benign liver masses.

PMID- 16641792
TI  - Radiofrequency ablation of liver tumors: the role of microbubble ultrasound
      contrast agents.
AB  - Radiofrequency ablation (RFA) is currently indicated for the treatment of primary
      and metastatic hepatic malignancies. Real-time ultrasound (US) is generally used
      during the procedure to guide electrode placement, but for evaluating the results
      of treatment, contrast-enhanced computed tomography and magnetic resonance
      imaging have traditionally been considered more effective. This view has changed,
      however, with the recent development of contrast-enhanced ultrasound (CEUS) (eg,
      using sulfur hexafluoride microbubbles), which can provide valuable information
      on the effects of RFA more rapidly and economically than computed tomography or
      magnetic resonance imaging without exposing the patient to ionizing radiation. In
      our center, CEUS is performed in patients with liver tumors before and
      immediately after RFA, in selected cases during the procedure as well, and in the
      follow-up. Between January 2003 and June 2005, we performed CEUS on 350 patients
      scheduled for RFA of primary or metastatic liver tumors. In 14 (13.4%) of the 96
      patients whose disease was metastatic, CEUS revealed lesions that had been missed
      on the conventional US examination. In most of these cases, the result was a more
      complete treatment performed under CEUS guidance. In the remaining 2 (14%) of 14,
      the results of the examination allowed us to avoid subjecting the patient to
      useless treatment. In our experience, the use of CEUS also improved the
      management and follow-up of patients undergoing interstitial therapy.

PMID- 16641793
TI  - Aortic endografts: detecting endoleaks using contrast-enhanced ultrasound.
AB  - Evaluation of aortic endografts is an exciting new application for contrast
      enhanced ultrasound. Detection of endoleaks is critical as they may lead to
      progressive enlargement of a treated aneurysm with a risk of aneurysm rupture. In
      this article, contrast enhanced ultrasound is presented as a potentially
      accurate, safe and economical alternative to CTA, the current practice standard,
      for endoleak detection.

PMID- 16641794
TI  - The kidney: imaging with microbubble contrast agents.
AB  - Conventional ultrasonography of the kidney is faced by limitations due to the
      poor contrast of B-mode imaging for parenchymal disease and limited sensitivity
      of color Doppler for the detection of intracortical capillaries and deep
      pedicular vessels. Ultrasound contrast agents (USCAs) overcome these limitations,
      allowing the development of new applications for renal blood flow imaging and
      quantification. These improvements result from the increased acoustic response
      obtained from the microbubbles, as well as from the development of pulse
      sequences for bubble-specific imaging. In radiology, the liver has been
      considered as the primary target for contrast because USCAs allow both detection
      and characterization of focal lesions. The kidney has been less studied because
      USCA kinetics do not provide the same obvious potential for tumor
      characterization, and most clinical trials for contrast-enhanced renal imaging
      were conducted using color Doppler. Despite this, the kidney offers promising
      applications as USCAs improve the detection of abnormal microvascular and
      macrovascular disorders. Contrast-enhanced US may become the modality of choice
      for diagnosis of renal artery stenosis and detection of a perfusion deficit, as
      well as for characterization of indeterminate renal lesions, atypical cystic
      lesions, and the identification of acute pyelonephritis.

PMID- 16641795
TI  - Cellular and molecular imaging with targeted contrast ultrasound.
AB  - There is growing interest in the availability of methods for imaging disease at
      the level of the cellular and/or molecular mediators. Techniques for imaging
      molecular alterations have been develop for essentially all non-invasive cardiac
      imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on
      the detection of novel site-targeted contrast agents. These microbubbles or
      nanoparticles are retained within regions of a specific disease process, thereby
      allowing phenotypic characterization of tissue. Since most of these tracers
      remain within the intravascular space, the disease processes assessed must be
      characterized by antigens that are expressed within the vascular compartment.
      Accordingly, the pathologic states that have been targeted include inflammation,
      ischemia-and tumor-related angiogenesis, and thrombus formation; all of which are
      mediated in part by molecular events within the vascular space. This review
      describes: 10 different strategies that have been employed to target ultrasound
      contrast agents to regions of disease, 2) the unique challenges for imaging
      targeted ultrasound contrast agents, and 3) some of the early experience imaging
      molecular events in animal models of disease.

PMID- 16641820
TI  - Agreement in reported sexual partnership dates and implications for measuring
      concurrency.
AB  - OBJECTIVES: To describe the reliability of reported dates of first and last
      sexual exposure, as elicited from sexually transmitted disease/human
      immunodeficiency virus cases during routine contact investigation, and determine
      their adequacy for assessing concurrency. METHODS: We used contact tracing data
      from 5 studies in which both members of 774 dyads were interviewed and named each
      other as sex partners. We assessed partners' agreement on the dates of first and
      last exposure as related to precision (to the day, month, or year) of reported
      dates and demographic and behavioral characteristics of the dyad. We performed
      simulations that introduced reporting error, based on our observed data, to
      posited "true" temporal configurations of partnerships to assess the impact of
      unreliability in reporting on the measurement of concurrency. RESULTS: Thirty-two
      percent of dyads agreed on the exact date of first sexual exposure, and 36% did
      so for the date of last sexual exposure. Sixty-four percent agreed within 30 days
      on the date of first sexual exposure, and 81% did so for the date of last sexual
      exposure. The reliability of reported dates was positively related to the
      precision of the reports. Agreement on reported exposure dates was not
      meaningfully associated with any of the sociodemographic and behavioral variables
      available. Based on simulations, the positive predictive value of reported dates
      for estimating concurrency is approximately 80% over a wide range of conditions.
      CONCLUSIONS: These data suggest that the reliability of reported exposure dates
      is reasonably good but that estimating concurrency with reported dates is subject
      to some error. Data designed for the purpose and analyzed with adequate attention
      to the statistical and epidemiologic issues of assessing concurrency are needed.

PMID- 16641821
TI  - Coverage of antenatal syphilis screening and predictors for not being screened in
      Ulaanbaatar, Mongolia.
AB  - OBJECTIVES: To measure the coverage of antenatal syphilis screening and identify
      factors related to women not being screened. GOAL: To assess the syphilis control
      program in Mongolia. STUDY DESIGN: Antenatal care records of women in 16
      antenatal care clinics of 6 districts were reviewed. Additionally, postpartum
      women were interviewed to identify potential factors for not being screened.
      RESULTS: Among 3,519 antenatal records, the coverage of syphilis screening was
      77.7%. Of 2,735 screened women, 54 (2.0%) had reactive serological results and
      subsequently received treatment. Four late antenatal care comers delivered
      infants with congenital syphilis. Being unscreened was significantly associated
      with late antenatal care (odds ratio OR=2.6), lack of knowledge (OR=5.5), history
      of previous sexually transmitted infection (OR=3.7), and living far from
      screening services (OR=4.9). CONCLUSIONS: The coverage of antenatal syphilis
      screening is still low, with poor contact tracing. More efforts are needed to
      promote early antenatal care visit and improve syphilis screening systems.

PMID- 16641822
TI  - Prevalence and incidence of syphilis among South American transgender sex workers
      in Northern Italy.

PMID- 16641823
TI  - HIV risk behavior patterns, predictors, and sexually transmitted disease
      prevalence in the social networks of young Roma (Gypsy) men in Sofia, Bulgaria.
AB  - OBJECTIVES AND GOAL: This research studied predictors of high-risk sexual
      practices and sexually transmitted disease (STD) prevalence among Roma (Gypsy)
      men's social networks in Sofia, Bulgaria. STUDY DESIGN: Fifty-four socially
      active individuals, approached in Roma neighborhood venues, recruited members (n
      = 296) of their own networks into the study. Participants completed sociometric
      and risk behavior interviews and were tested for chlamydia, gonorrhea, syphilis,
      and trichomonas. RESULTS: Men had a mean of 7 partners in the past year. Fifty
      nine percent had multiple partners in the past 3 months. Seventy-three percent
      reported recent unprotected vaginal and 51% unprotected anal intercourse. Fifty
      nine percent of men had sex with other men in the past year. Twenty-two percent
      had one of the STDs. The social network to which an individual belonged accounted
      for 23% to 27% of variance in predicting sexual risk behavior. CONCLUSIONS: One's
      social network was the most powerful predictor of HIV risk behavior. HIV/STD
      prevention interventions directed toward entire social networks are especially
      promising.

PMID- 16641824
TI  - Prevalence of Chlamydia in young men in the United States from newly implemented
      universal screening in a national job training program.
AB  - OBJECTIVE: The objective of this study was to examine chlamydia prevalence and
      its risk factors from the first universal screening in socioeconomically
      disadvantaged young men. GOAL: The goal of this study was to evaluate the need
      for universal screening in young men. STUDY DESIGN: We calculated chlamydia
      prevalence by demographic and geographic characteristics from 51,478 men aged 16
      to 24 years who were screened from July 2003 to December 2004. RESULTS: Overall,
      chlamydia prevalence was 8.2%. Only 2.4% of the young men had sexually
      transmitted disease symptoms. Blacks had the highest prevalence (13.0%), whereas
      non-Hispanic whites had the lowest (3.1%). Men who smoked marijuana had a
      significantly higher prevalence compared with those who did not (11.9% vs. 6.4%).
      Men who used cocaine or PCP also had a significantly higher chlamydia prevalence
      compared with those who did not. Men who lived in the southern region of the
      United States had the highest prevalence. CONCLUSIONS: Chlamydial infection is
      highly prevalent among socioeconomically disadvantaged young men. Young men
      entering the National Job Training Program represent an important population for
      screening.

PMID- 16641825
TI  - Vaginal and rectal topical microbicide development: safety and efficacy of 1.0%
      Savvy (C31G) in the pigtailed macaque.
AB  - BACKGROUND: A 1.0% gel formulation of C31G, a surfactant, has been shown to have
      in vitro antiviral and antibacterial activity. GOAL: The goal of this study was
      to evaluate the safety and efficacy of vaginal and rectal applications of 1.0%
      Savvy (C31G) in the nonhuman primate model. STUDY DESIGN: The safety of repeated
      1.0% C31G application was evaluated by microflora, pH, vaginal biopsy,
      colposcopy, and rectal lavage. Efficacy in preventing chlamydial infection was
      documented by culture, nucleic acid amplification tests, and serology. RESULTS:
      Repeated applications of Savvy (1.0% C31G) were not associated with significant
      changes in pH, microflora, or inflammatory infiltrates on tissues. No significant
      differences in epithelial desquamation were noted after rectal product use
      compared with placebo. Four of 6 animals were protected from chlamydial infection
      after pretreatment with Savvy. C31G was shown to be safe to both vaginal and
      rectal mucosal tissues and to the microflora with repeated daily use. CONCLUSION:
      Savvy has an acceptable safety profile after repeated vaginal and rectal use. A
      single intravaginal application of 1.0% C31G provided partial protection from
      acquiring cervical chlamydial infection.

PMID- 16641826
TI  - Men who have sex with men and women: a unique risk group for HIV transmission on
      North Carolina College campuses.
AB  - OBJECTIVE: To better understand the role that men who have sex with men and women
      (MSM/W) play in the spread of HIV in young adults in North Carolina, we
      determined the prevalence of MSM/W among newly diagnosed HIV-infected men,
      compared social and behavioral characteristics of this group with MSM and MSW,
      and examined the sexual networks associated with HIV-infected college students
      among these groups. METHODS: We reviewed state HIV surveillance records for all
      new diagnoses of HIV in males 18 to 30 years living in North Carolina between
      January 1, 2000, and December 31, 2004. RESULTS: Of 1,105 records available for
      review, 15% were MSM/W and 13% were college students. Compared with MSM, MSM/W
      were more likely to be enrolled in college, to report >10 sex partners in the
      year before diagnosis, or have sex partners who were also MSM/W. Sexual network
      analysis of the HIV-infected college students revealed that MSM/W occupied a
      central position. Of 20 individuals who described themselves as either MSW or
      abstinent at the time of their initial voluntary counseling and testing visit,
      80% reported that they were either MSM or MSM/W during follow up. DISCUSSION:
      MSM/W represent a unique risk group within the population of MSM that deserve
      further investigation. College MSM/W appear to occupy a unique, central place in
      the network of HIV-infected students.

PMID- 16641827
TI  - Inadequate syphilis screening among women with prenatal care in a community with
      a high syphilis incidence.
AB  - OBJECTIVES AND GOAL: This study was designed to evaluate the extent to which
      pregnant women in a community with a high syphilis incidence were screened for
      syphilis according to standard recommendations of twice during prenatal care and
      at labor and delivery. STUDY DESIGN: Labor and delivery records from 4 hospitals
      in Miami-Dade County, Florida, were abstracted to obtain maternal and prenatal
      care characteristics and syphilis screening practices. RESULTS: Of the 1991
      women, records indicated that 1655 (83%) were screened at least once during
      prenatal care, 220 (11%) were screened twice during prenatal care before
      delivery, and 184 (9%) were screened twice during prenatal care and at delivery.
      Attending a private clinic, having more than adequate prenatal care and having
      private insurance were associated with not being screened at least twice before
      delivery. CONCLUSIONS: Few women were screened according to standard
      recommendations, and provider or institutional-related factors affected adequacy
      of screening.

PMID- 16641828
TI  - Well-deserved credit for bipolar disorder.

PMID- 16641829
TI  - Specific phobia: a disorder of fear conditioning and extinction.
AB  - Specific phobia is the most prevalent of the anxiety disorders. Although there
      have been relatively few studies of its psychobiology and pharmacotherapy, there
      is a rich laboratory of literature on fear conditioning and extinction and a
      clear evolutionary perspective. Advances in the cognitive-affective neuroscience
      of fear processing may ultimately lead to new approaches to the clinical
      management of phobias.

PMID- 16641830
TI  - Pure mutism due to simultaneous bilateral lenticulostriate artery territory
      infarction.
AB  - A case of pure mutism without pseudobulbar palsy and other neurological findings
      resulting from simultaneous bilateral lenticulostriate artery territory
      infarction is presented. A 45-year-old woman suffered a transient ischemic attack
      with nonfluent aphasia and right hemiparesis. Six months later, she developed
      pure mutism without oral apraxia, pseudobulbar signs, and motor deficits.
      Magnetic resonance imaging revealed bilateral infarction in the lentiform nucleus
      regions. In the available data, there is only one report of simultaneous
      bilateral lenticulostriate infarction. To date, in all reported cases of mutism
      of subcortical vascular origin there are also various degrees of pseudobulbar
      signs and motor deficits and the responsible lesions are mostly consecutive. The
      case presented here is the first to show pure vascular mutism without other
      neurological findings.

PMID- 16641831
TI  - Delirium following ingestion of marijuana present in chocolate cookies.
AB  - OBJECTIVE: To describe a case of marijuana-induced delirium and the techniques
      used to detect psychoactive agents and metabolites in urine. METHODS: A case of
      delirium following involuntary ingestion of cannabis is described. A urine sample
      was analyzed applying various chemical procedures, using high-resolution gas
      chromatography coupled with mass spectrometry technique. 11-Nor-delta9
      tetrahydrocannabinol-9-carboxylic acid was quantified by the methodology for
      steroids and cannabis. RESULTS: A 26-year-old man was hospitalized with severe
      agitation and psychotic behavior 36 hours after suspected involuntary ingestion
      of cannabis contained in a brigadeiro, a typical Brazilian cookie, consumed
      during a party. Treatment with neuroleptics resulted in complete regression of
      the symptoms over 2 weeks. The urine sample revealed marijuana ingestion,
      demonstrated by the presence of its metabolite, 11-nor-delta9
      tetrahydrocannabinol-9-carboxylic acid in high concentration. No other
      investigated substance was found in the patient's urine. CONCLUSION: Severe
      delirium can follow oral ingestion of cannabis integrated into homemade cookies.

PMID- 16641832
TI  - Bipolar disorder and advances in neuroimaging: a progressive match.

PMID- 16641833
TI  - Advances in magnetic resonance imaging methods for the evaluation of bipolar
      disorder.
AB  - This article reviews the current state of magnetic resonance imaging techniques
      as applied to bipolar disorder. Addressed are conventional methods of structural
      neuroimaging and recently developed techniques. This latter group comprises
      volumetric analysis, voxel-based morphometry, the assessment of T2 white matter
      hyperintensities, shape analysis, cortical surface-based analysis, and diffusion
      tensor imaging. Structural analysis methods used in magnetic resonance imaging
      develop exponentially, and now present opportunities to identify disease-specific
      neuroanatomic alterations. Greater acuity and complementarity in measuring these
      alterations has led to the generation of further hypotheses regarding the
      pathophysiology of bipolar disorder. Included in the summary of findings is
      consideration of a resulting neuroanatomic model. Integrative issues and future
      directions in this relatively young field, including multi-modal approaches
      enabling us to produce more comprehensive results, are discussed.

PMID- 16641834
TI  - Functional magnetic resonance imaging studies in bipolar disorder.
AB  - Abnormalities in brain activation using functional magnetic resonance imaging
      (fMRI) during cognitive and emotional tasks have been identified in bipolar
      disorder patients, in frontal, subcortical and limbic regions. Several studies
      also indicate that mood state may be differentiated by lateralization of brain
      activation in fronto-limbic regions. The interpretation of fMRI studies in
      bipolar disorder is limited by the choice of regions of interest, medication
      effects, comorbidity, and task performance. These studies suggest that there is a
      complex alteration in regions important for neural networks underlying cognition
      and emotional processing in bipolar disorder. However, measuring changes in
      specific brain regions does not identify how these neural networks are affected.
      New analytical techniques of fMRI data are needed in order to resolve some of
      these issues and identify how changes in neural networks relate to cognitive and
      emotional processing in bipolar disorder.

PMID- 16641835
TI  - The neurophysiology of childhood and adolescent bipolar disorder.
AB  - INTRODUCTION: Children and adolescents with bipolar disorder often present with
      higher rates of mixed episodes, rapid cycling, and co-occurring attention
      deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear
      whether the differences in clinical presentation between youth and adults with
      bipolar disorder are due to differences in underlying etiologies or developmental
      differences in symptom manifestation. Neuroimaging studies of children and
      adolescents with bipolar disorder may clarify whether neurobiological
      abnormalities associated with early- and adult-onset bipolar disorder are
      distinct. Moreover, children and adolescents with bipolar disorder are typically
      closer to their illness onset than bipolar adults, providing a window of
      opportunity for identifying core neurobiological characteristics of the illness
      (ie, disease biomarkers) that are independent of repeated affective episodes and
      other confounding factors associated with illness course. METHODS: Peer-reviewed
      publications of neuroimaging studies of bipolar children and adolescents were
      reviewed. RESULTS: Structural, neurochemical, and neurofunctional abnormalities
      in prefrontal and medical temporal and subcortical limbic structures, including
      the striatum, amygdala, and possibly hippocampus, are present in children and
      adolescents with bipolar disorder. CONCLUSION: Differences between
      neurobiological abnormalities in bipolar youth and adults as well as
      recommendations for future research directions are discussed.

PMID- 16641836
TI  - Brain network dysfunction in bipolar disorder.
AB  - Bipolar disorder is a common psychiatric condition with significant associated
      morbidity and mortality. Despite its significance, the neurophysiology and
      neuropathology of this illness is incompletely understood. Recent advances in
      neuroimaging techniques have helped to begin clarifying these areas.
      Specifically, bipolar disorder appears to arise from abnormalities within
      discrete brain networks (eg, the anterior limbic network). The expression of the
      symptoms of bipolar disorder does not appear to result from single, localized
      brain lesions, but rather are emergent properties of dysfunction of these brain
      networks. As neuroimaging techniques continue to improve, the underlying neural
      basis of bipolar disorder will be clarified.

PMID- 16641837
TI  - Preventing clinical deterioration in the course of schizophrenia: the potential
      for neuroprotection.
AB  - Schizophrenia, which has both genetic and environmental causes, is associated
      with persistent symptoms and severe functional disability. The illness lies
      dormant during the premorbid phase and begins to express itself during
      adolescence or early adulthood. Clinical progression and deterioration reaches a
      plateau in which the patient is said to be in the chronic phase of illness and at
      which point restoration of prior functioning is unlikely. The severe deficits
      associated with schizophrenia are often the result of progression of illness due
      to lack of appropriate treatment. However, recent advances in neuropsychiatry
      have led to very early identification of individuals at risk for psychosis, even
      during the prodromal stage when psychosis has not yet manifested clinically.
      While research has demonstrated that the efficacy of antipsychotics is limited
      when used during the chronic phase of illness, these medications can effectively
      control symptoms and prevent progression of illness when used during the early
      stages of illness. The evidence of neural degeneration in the pathophysiology of
      schizophrenic illness suggests that there may be treatment opportunities through
      neural protection. Neuroprotection, which refers to treatment that helps maintain
      central nervous system functionality in response to neurobiologic stress, may be
      responsible for prevention of disease progression and deterioration. In this
      monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic
      illness in relation to the concepts of progression and deterioration. Next,
      Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative
      components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the
      neuroprotective aspects of therapeutic interventions in schizophrenia.

PMID- 16641838
TI  - Leading the way: advances in the diagnosis, treatment, and management of
      neuropsychiatric illnesses.

PMID- 16641839
TI  - Angioedema and maculopapular eruptions associated with carbamazepine
      administration.
AB  - Cutaneous rashes and eruptions can be caused by many medications, including
      carbamazepine. The presentation can be varied depending on severity. Cutaneous
      eruptions occur in 3% of individuals administered carbamazepine. Angioedema, a
      rare side effect of carbamazepine, involves vascular leakage in dermis and
      subcutis mediated by immunoglobulin E and/or bradykinins. Angioedema is more
      common in females and in the third decade of life. We report the case of a 27
      year-old Indian woman who developed maculopapular rash and angioedema secondary
      to carbamazepine administration. The patient responded successfully to withdrawal
      of the drug and treatment with antihistamines. Due to the potentially life
      threatening complications of this condition and the increasing use of
      anticonvulsants in the treatment of mood disorders, psychiatrists must be aware
      of the diagnosis and treatment of this condition.

PMID- 16641840
TI  - The dynamics of insight in the prodrome of schizophrenia.
AB  - INTRODUCTION: Schizophrenia is characterized by diminished insight, which
      fluctuates with disease progression. Insight deterioration in the prodrome of
      schizophrenia is poorly understood. Despite pharmacologic treatment, including
      early interventions, there is a high risk of relapse and need of acute care in
      schizophrenia patients. OBJECTIVE: To study if insight deterioration occurs
      during the prodrome and if insight preservation early in the illness might
      predict a better prognosis. METHODS: Data was collected retrospectively from the
      records of 24 patients initially diagnosed with schizophrenia during a 2-year
      period. Patients' progress was then tracked over a 3-year period. Insight was
      determined by a physician's subjective evaluation, patient interest and
      participation in treatment planning, and patient accuracy in reporting behaviors
      and symptoms when compared with reports from collaterals. RESULTS: Ten patients
      were determined to have insight regarding the developing illness at different
      presentations at the hospital. Insight preservation correlated with less need for
      emergency visits and fewer hospitalization days (P<.005). It was also associated
      with more depressive and anxious mood (P<.000). Patients and family members
      described early, ego-dystonic perceptual disturbances followed by diminished
      insight. Awareness into the illness, symptoms, and attribution of symptoms to the
      illness fluctuated at different presentations in the insight group. In the other
      group, insight was nil at each presentation after the psychotic debut.
      CONCLUSION: Most patients maintain insight during the perceptual disturbance
      phase. Insight diminishes as the early delusional phase sets in. Higher levels of
      preserved insight seem to correlate with less need for acute treatment. Further
      research in this area is warranted for determining if early insight oriented
      interventions in the prodromal phase can improve the prognosis of schizophrenia.

PMID- 16641841
TI  - Transdermal selegiline: the new generation of monoamine oxidase inhibitors.
AB  - The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to
      concerns about food and drug interactions and waning physician experience.
      Evidence indicates that MAOIs are effective in depressive disorders, in
      particular depression with atypical features. Efforts to address safety issues
      have led to the development of more selective and reversible MAOIs, such as
      moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been
      approved for the adjunctive treatment of Parkinson's disease at low doses. At
      higher doses, oral selegiline is also effective in major depressive disorder
      (MDD) but loses its selectivity and has the potential for tyramine interactions.
      To overcome these problems, a transdermal formulation of selegiline, the
      selegiline transdermal system (STS), was developed with novel pharmacokinetic and
      pharmacodynamic properties. Compared with oral administration, transdermal
      selegiline leads to sustained plasma concentrations of the parent compound,
      increasing the amount of drug delivered to the brain and decreasing metabolite
      production. In addition, STS allows targeted inhibition of central nervous system
      monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in
      the gastrointestinal and hepatic systems, thereby reducing the risk of
      interactions with tyramine-rich foods (the "cheese-reaction"). Clinical trials
      have found 6 mg/24 hours of STS to be effective in MDD without the need for
      dietary restrictions. The efficacy and safety profile of STS supports its use in
      MDD. It is possible that STS may demonstrate benefit in MDD with atypical
      features or MDD resistant to other antidepressants. However, more research is
      needed. Clinicians should familiarize themselves with the properties and
      indications for the new generation of MAOIs.

PMID- 16641842
TI  - Efficacy and safety of lamotrigine for adults with bipolar disorder in a private
      practice setting.
AB  - INTRODUCTION: Lamotrigine is approved by the Food and Drug Administration for
      maintenance therapy in patients with bipolar I disorder. However, several studies
      of acute-phase and maintenance treatment support the efficacy of lamotrigine for
      bipolar I and bipolar II disorders. This chart review was performed to assess the
      efficacy and safety of lamotrigine in the treatment of bipolar disorder in a
      private psychiatric practice setting and to investigate differences in response
      among patients with different diagnostic subtypes of bipolar disorder. METHODS:
      The charts of 587 adult outpatients with a primary diagnosis of bipolar disorder
      who received treatment with lamotrigine in a private practice setting between
      July 1998 and May 2004 were reviewed retrospectively. Treatment response was
      assessed with the Clinical Global Impression-Improvement scale and was defined as
      achievement of a score of <2. RESULTS: Three hundred forty-nine patients (59.5%)
      responded to lamotrigine. Response rates were comparable among patients with
      bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise
      specified, and among patients with bipolar I disorder who presented with
      depressive, manic, or mixed episodes. Nonserious rash (12.8%) and headache (2.9%)
      were the most frequently reported adverse events. CONCLUSION: These results
      suggest that lamotrigine is effective and well-tolerated in the treatment of
      bipolar disorder across the spectrum of subtypes of the illness.

PMID- 16641843
TI  - Multisomatoform disorder: agreement between patient and physician report of
      criterion symptom explanation.
AB  - OBJECTIVE: To determine the level of agreement between patients and expert
      physicians in whether criterion multisomatoform (MSD) symptoms are explained.
      METHODS: We systematically collected reports from 280 primary care patients about
      whether they had suffered from any of 15 criterion MSD symptoms in the past month
      and whether they had received a medical explanation from a physician for positive
      criterion symptoms. The research team compared MSD symptom diagnoses derived from
      patient report with MSD symptom diagnoses derived from an expert physician
      report. RESULTS: MSD symptom diagnoses derived from patient report had 98.7%
      sensitivity, 97.9% specificity, 89.3% positive predictive value, and 99.7%
      negative predictive value compared with MSD symptom diagnoses derived from an
      expert physician report. Analysis demonstrated that 15.0% of patients met symptom
      criteria for MSD, according to patient and physician report; 83.0% failed to meet
      symptom criteria for MSD, according to patient and physician report; 1.8% of
      patients met symptom criteria for MSD, according to patient report but not
      physician report, while 0.2% met symptom criteria for MSD according to physician
      report but not by patient report. CONCLUSION: Patients demonstrated high
      agreement with a physician expert in somatization about whether criterion MSD
      symptoms are explained, suggesting revised screeners may accurately identify
      somatizing patients.

PMID- 16641844
TI  - An open-label trial of OROS methylphenidate in adults with late-onset ADHD.
AB  - INTRODUCTION: Many adults with current impairing symptoms of attention
      deficit/hyperactivity disorder (ADHD) do not report an age at onset before 7
      years of age and cannot, therefore, be assigned the full Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnosis of
      ADHD. We hypothesized that treatment with oral release osmotic system (OROS)
      methylphenidate (MPH) will be safe and efficacious for the treatment of adults
      with late-onset ADHD. METHOD: This was a 6-week, open-label, prospective
      treatment study of OROS MPH monotherapy in 36 adult patients with late-onset ADHD
      (onset later than the required 7 years of age) using standardized instruments for
      diagnosis and a robust oral daily dose of up to 1.3 mg/kg/day. Symptom severity
      was assessed with the Adult ADHD Investigator Symptom Report Scale (AISRS) and
      the Clinical Global Impression (CGI) scale. RESULTS: Subjects reported robust
      current symptoms of ADHD at pre-treatment baseline (11.1+/-2.8 DSM-IV symptoms),
      but had an atypical mean age at onset of 14.2+/-8.6 years. Treatment with OROS
      MPH at an average daily dose of 78.2+/-29.4 mg was associated with a
      statistically and clinically significant reduction in ADHD symptoms relative to
      baseline as assessed through the AISRS (-16.4+/-10.5; P<.001). Using a
      categorical definition of response (CGI-I much or very much improved), a majority
      (n = 26; 72%) of subjects were rated as improved at endpoint. CONCLUSION: These
      results extend previous findings in adults with full ADHD to adults meeting
      criteria for late-onset ADHD and support the need for further controlled clinical
      trials in this population.

PMID- 16641847
TI  - Premenstrual syndrome in adolescents: diagnosis and treatment.
AB  - It is estimated that 60-80% of menstruating women experience some degree of
      premenstrual symptomatology; however the diagnosis of premenstrual syndrome (PMS)
      or premenstrual dysphoric disorder (PMDD) is assigned, using defined criteria, to
      those women whose lives are significantly affected by moderate to severe
      symptoms. Though these diagnoses are not frequently made in the adolescent group,
      the literature suggests that a similar proportion of teens would also meet
      criteria for PMS/PMDD. In adolescents, treatment should begin with education and
      lifestyle changes; however, many of the treatments used commonly in adults can
      also be employed safely in severe adolescent cases.

PMID- 16641848
TI  - Adolescent menstrual health.
AB  - Attention to pubertal development and menstrual health is an important aspect of
      primary care for adolescents. Textbooks may not provide sufficient evidence-based
      guidance to facilitate the early detection of gynecologic disease states and
      conditions. Conversely, the typical guidelines for pubertal development may lead
      to over-evaluation of normal girls. Chaotically irregular and unpredictable
      bleeding is NOT the norm during adolescence. On the contrary, although many early
      menstrual cycles are anovulatory, most adolescents have menstrual cycles that
      fall within the parameters of 21-45 days. Adolescents with menstrual bleeding
      that is less frequent than every 45 days, is prolonged > 7 days, or is
      excessively heavy should be evaluated in order to detect conditions such as
      eating disorders, polycystic ovary syndrome, and von Willebrand disease.
      Clinicians who attend to adolescent menstrual cycles can help set the stage for
      future health.

PMID- 16641849
TI  - Menstrual patterns under hormonal contraception in adolescent girls and young
      women.
AB  - Adolescents are more likely to discontinue hormonal contraception because of
      disturbances in their menstrual patterns. Menstrual disturbances occur as
      spotting, breakthrough bleeding, as well as missed withdrawal bleeding depending
      on both the prevailing levels of estrogens and the more or less suppressed
      endometrium. Patients on cyclic prescribed oral combined micro-pills are found to
      have the fewest menstrual disturbances compared with all other hormonal regimens.
      Combined micro-pills as long term therapy should be given for medical indications
      only. Oral gestagen-only mini-pills are suitable for adolescent girls when
      estrogens are contraindicated. Irregular bleeding was found in more than 50% of
      patients. Long term contraceptives of all hormonal contraceptives show the
      highest rate of menstrual disturbance. They are suitable for adolescent girls in
      special indications only.

PMID- 16641850
TI  - Menstrual disorders during adolescence.
AB  - During the post-menarcheal years several kinds of menstrual disorders can be
      observed, such as abnormal uterine bleeding, primary and secondary dysmenorrhea,
      premenstrual syndrome, primary and secondary amenorrhea and oligomenorrhea.
      Abnormal uterine bleeding and especially the subtype of dysfunctional uterine
      bleeding is the most urgent gynecological problem during adolescence, while
      dysmenorrhea is the most frequent one for which adolescents and their parents
      refer to a physician. Normal menstrual cycle physiology as well as definitions of
      all the above menstrual disorders is briefly mentioned before going on with
      dysfunctional uterine bleeding and dysmenorrhea.

PMID- 16641851
TI  - Painful menstruation.
AB  - Painful menstruation is a cyclic painful condition that adversely affects the
      woman's wellbeing for a large part of her life. Its pathogenesis is not always
      understood. Prostaglandins seem to be intimately involved in primary
      dysmenorrhoea although it is difficult to understand the underlying cause for
      their excessive secretion. Abnormalities in plasma steroid levels could account
      for the disturbance, especially significantly elevated plasma levels of estradiol
      in the luteal phase. Plasma levels of vasopressin appear to be higher in women
      with dysmenorrhea suggesting a possible aetiological role in the uterine
      prostaglandin synthesis. The main aim of diagnosis is to distinguish those cases
      with secondary dysmenorrhoea due to endometriosis and chronic pelvic inflammatory
      disease and treat them accordingly although the exact role of endometriosis
      remains unclear. The development of sonographic and magnetic resonance imaging
      techniques (MRI) allow pre-operative diagnosis of adenomyosis, a difficult to
      diagnose cause of dysmenorrhea and pelvic pain. Medication is usually required
      for all cases of moderate to severe painful menstruation. Apart from
      pharmacological agents, several techniques have been used including relaxation
      therapy, hypnosis, manipulation, psychotherapy, acupuncture, biofeedback
      techniques, surgery e.g. Despite the high prevalence of painful menstruation, its
      frequency and severity is very often underestimated.

PMID- 16641852
TI  - Hormonal contraception compliance in teenagers.
AB  - Contraception compliance is still an issue among teenagers, contributing in no
      lesser extent to high levels of adolescent pregnancies. This article reviews some
      of the factors that contribute to the inconsistency of contraceptive use and
      higher levels of noncompliance by adolescents, among them the impact of age,
      knowledge, and availability of contraceptive options. Attention is also paid to
      cultural and behavioral aspects, including the partner's attitude, professional
      attitudes, the user-provider relationship, and information. Some strategies aimed
      at enhancing compliance are discussed.

PMID- 16641853
TI  - Pregnancy and abortion in adolescents.
AB  - Pregnancy and its complications are the leading causes of morbidity and mortality
      in young women in the developing world. These issues are discussed, and
      recommendations are made for their alleviation.

PMID- 16641854
TI  - Adolescent pregnancy and perinatal outcome.
AB  - Adolescent pregnancy is associated with adverse maternal and fetal effects.
      Potential risk factors involve early dating behavior, early initiation of
      smoking, alcohol and substance abuse, low academic interest, single-parent
      families and, above all, poverty. Girls younger than 18 years and not legally
      majors are psychologically and socially underdeveloped, presenting higher
      obstetrical risks. Maternal complications due to adolescent pregnancy include,
      among others: anemia; pregnancy induced hypertension; sexually transmitted
      diseases; and premature labor and delivery. The most common complications
      concerning the infant are related to: low birth weight, due either to prematurity
      or intrauterine growth restriction; infection; chemical dependence (due to
      maternal substance abuse); sudden infant death syndrome; and increased morbidity
      and mortality during the 1st year of age. In addition, education of teenage
      mothers on the importance of pre-and postnatal care can reduce the poor perinatal
      outcome of both mother and infant.

PMID- 16641855
TI  - The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes
      interplay.
AB  - Vertebrates respond to stress with activation of the hypothalamic-pituitary
      adrenal (HPA) axis, the adrenergic and the autonomic nervous systems. The
      principal central nervous system regulators of the HPA axis are corticotropin
      releasing hormone (CRH) and antidiuretic hormone (AVP). Apart from in the central
      nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium,
      endometrium, placenta, testis and elsewhere. The activation of the HPA axis
      during stress affects all body systems. The reproductive axis is inhibited by the
      HPA axis for the sake of saving energy. The changes to the hypothalamic-pituitary
      gonadal (HPG) axis during stress are species-specific, and depend on the type and
      duration of the stimulus. Several conditions may be associated with altered
      regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and
      pregnancy in the third trimester are all characterized by HPA axis activation. In
      contrast, during the postpartum period, HPA axis suppression is implicated in the
      "postpartum blues". The actions of CRH are also essential in fetal development
      and neonatal survival.

PMID- 16641856
TI  - Precocious puberty.
AB  - The term precocious puberty encompasses a group of heterogeneous conditions that
      range from variants of normal to slowly progressive and rapidly progressive
      maturation of both sexes. It is defined as the appearance of secondary sex
      characteristics before the age of 8 in girls and 9 in boys. The clinician who is
      evaluating a child with precocious puberty should be aware of the normal events
      of puberty, the ages at which pubertal milestones are achieved and the tempo of
      pubertal progression. The mechanisms involved in the onset and progression of
      normal puberty are briefly discussed in this article. The diverse etiology of
      precocious puberty, the diagnostic evaluation of the patient including clinical,
      laboratory and radiological investigation as well as problems associated with
      precocious puberty and indications for treatment and treatment modalities are
      further discussed in the article.

PMID- 16641857
TI  - Development and biological function of the female gonads and genitalia in IGF-I
      deficiency -- Laron syndrome as a model.
AB  - Laron syndrome (LS) or primary GH insensitivity is a unique human model to study
      the effects of congenital IGF-I deficiency. Within our cohort of 63 patients with
      LS, 15 female patients were regularly followed since birth or infancy, throughout
      puberty. We observed that they were short at birth, with small genitalia and
      gonads -- during puberty, developed delayed puberty but eventually reached
      between 16 and 19 1/2 years full sexual development. Reproduction is unaffected
      at a young adult age. It is concluded that IGF-I in concert with the sex hormones
      has a modulatory but not essential function on female sexual development and
      maturation.

PMID- 16641858
TI  - Growth and long-term hormonal therapy.
AB  - Sex hormone replacement therapy (HRT) in the female adolescent has the following
      goals: 1. to mimic physiologic puberty; 2. to enhance normal growth; 3. to induce
      and maintain normal menstruation, 4. to support normal bone maturation and
      calcification; 5. to initiate and maintain normal brain cell growth and brain
      plasticity; and 6. to preserve the woman's psycho-sexual well-being. A
      physiologic peak bone mass during puberty and young adulthood is achieved when
      HRT is started by the age of 12. Estrogen has a biphasic effect on longitudinal
      growth, stimulatory at low doses and inhibitory at high doses. Therefore HRT in
      the adolescent girl is initiated with low doses of estrogen which progressively
      increase during a two-year period. This facilitates normal longitudinal growth
      and normal growth of the uterus for normal menstruation and future pregnancy with
      a donor oocyte. Whether HRT will continue past the normal age of menopause is
      still controversial.

PMID- 16641859
TI  - Non-classical congenital adrenal hyperplasia.
AB  - Deficiency of 21-hydroxylase constitutes the most frequent form of Congenital
      adrenal hyperplasia (CAH) and is classified into classical and nonclassical (NC)
      forms. The type of the molecular defect determines the severity of the phenotype
      with a high degree of concordance for the classical genotypes but with lower
      concordance for the NC genotypes. The clinical expression of NC-CAH is quite
      variable ranging from an asymptomatic state to premature pubarche, hirsutism,
      acne, menstrual irregularities, infertility and increased rate of spontaneous
      abortions. Basal and/or ACTH stimulated 17-hydroxyprogesterone (17OHP) values, >
      5 ng/ml and >10 ng/ml, respectively are currently applied to diagnose NC-CAH.
      Glucocorticoid administration to patients with NC-CAH is determined by the
      clinical manifestations. During pregnancy, steroid replacement therapy and
      adequate monitoring reduce the risk of spontaneous abortions. CYP21A2 genotyping
      of the partner of a prospective mother with NC-CAH is controversial. Most likely
      it should be performed if the mother carries a classical mutation.

PMID- 16641860
TI  - Hyperandrogenemia: pathophysiology and its role in ovulatory dysfunction in PCOS.
AB  - The most common hormonal disorder that infertile women suffer from is
      hyperandrogenemia, a disorder believed to show its first signs even from puberty.
      We discuss the impact of hyperandrogenemia on the normal ovary as well as its
      potential role and contribution to anovulation and infertility. The early
      diagnosis and management of hyperandrogenemia in women has been proved to be
      essential for their health and fertility.

PMID- 16641861
TI  - Polycystic ovarian disease: the adrenal connection.
AB  - Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia,
      ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen
      production in PCOD comes primarily from the ovaries. However, in about 40% of
      patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate,
      Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the
      adrenal in the PCOD is suggested by the presence of adrenal androgen excess in
      PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as
      in women with adrenal tumors. However, the cause of adrenal androgen
      hypersecretion is not yet fully understood but it may include endogenous
      hypersecretion of the zona reticularis of unclear cause, hypersecretion of
      cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal
      enzymatic defects etc. This short review covers the aspects of adrenal androgen
      hypersecretion in PCOD.

PMID- 16641862
TI  - Treatment options of polycystic ovary syndrome in adolescence.
AB  - The polycystic ovary syndrome (PCOS) is defined as a syndrome of hyperandrogenism
      and chronic anovulation in the absence of other underlying pituitary or adrenal
      disorders. PCOS often presents in adolescence and is the commonest cause of
      menstrual disorders and hirsutism. Premature adrenarche and hirsutism that occur
      before puberty have been associated with PCOS. The etiology of the syndrome is as
      yet uncertain. Theories have focused on intrinsic defects in the ovarian and
      adrenal steroidogenesis, and on the role of insulin resistance in modifying
      reproductive function. Insulin resistance associated with PCOS confers a markedly
      increased risk of impaired glucose tolerance and type 2 diabetes mellitus in
      adolescent girls, as in premenopausal women. Therapeutic considerations focus on
      the management of menstrual irregularities and hyperandrogenism, as well as on
      the prevention of the metabolic consequences of the syndrome.

PMID- 16641863
TI  - Hormone replacement treatment in Turner syndrome.
AB  - Turner syndrome is one of the most common sex chromosome abnormalities with an
      incidence of 1:2500 female newborns, characterized by short stature, gonadal
      dysgenesis in 85-90% of cases, special neurocognitive profiles and cardiac and
      renal abnormalities. Hormone replacement treatment should be initiated at a
      physiological age in these patients who do not enter puberty spontaneously and
      should be continued up to the age of normal menopause. The age-appropriate and
      adequate initiation of hormone replacement therapy has many beneficial effects in
      many aspects such as: the development of secondary sexual characteristics at an
      age-appropriate time; better psychosocial functioning and integration in the peer
      group during adolescence; the improvement of bone mineral density; normal uterine
      growth; and, therefore, the possibility of the accomplishment of an uneventful
      pregnancy after assisted reproduction and the fulfillment of motherhood. It is
      crucial that these women understand that hormone replacement is a long-term
      treatment.

PMID- 16641864
TI  - Predictors of bone loss in young women with restrictive eating disorders.
AB  - OBJECTIVES: To evaluate the influence of Body Mass Index, body composition and
      hormonal factors on bone mass in young women with amenorrhea related to
      restrictive eating disorders. DESIGN: Descriptive study of 55 patients with
      secondary amenorrhea due to restrictive eating disorders and 14 healthy girls
      used for comparison. Assessment of Bone Mineral Density, Fat Mass and Lean Mass
      by DEXA and of the serum hormonal profile. RESULTS: Patients had lower BMI, lower
      Fat Mass and lower Bone Mass compared to controls; their serum levels of LH,
      FT(3), DHEAS, Insulin and Leptin were significantly reduced. Low Bone Density,
      especially in the lumbar region, correlated with concentrations of FT(3),
      Cortisol, Insulin and Leptin, hormones expressive of metabolic adjustment to
      malnutrition. Lean Mass was a strong predictor of osteopenia and osteoporosis.
      CONCLUSIONS: Hormonal nutritional markers, together with soft tissue composition
      measurements, are viable options for ongoing monitoring of subjects with eating
      disorders.

PMID- 16641865
TI  - Health education for youth.
AB  - Recent surveys monitoring health behavior in children and adolescents in Europe,
      Canada and the USA are reporting worrisome data in terms of health-risk behavior.
      Childhood and adolescence are critical periods in life for taking preventive
      measures, since this is the time when health-related behavior and lifestyles have
      their beginnings. The present paper attempts to introduce the art and science of
      health education with the ultimate goal of stressing the fact that health and
      education are strongly associated. Approaches to health education, models of
      intervention and recommendations by leading authors in the field are presented.
      Suggestions for sex education in children and adolescents are provided.

PMID- 16641866
TI  - Hysterography -- new techniques.
AB  - For many years hysterosalpingography has provided images of the lumen of the
      fallopian tubes and the uterine cavity that were not available by other
      diagnostic modalities. In our days the development of new imaging and endoscopic
      techniques has limited its indications. In this paper we will discuss the current
      use of hysterosalpingography and the new techniques that have been developed such
      as sonohysterography.

PMID- 16641867
TI  - Concealed female external genitals: possible morpho-psychological clue to unique
      emotional and cognitive evolutionary matrix of man.
AB  - Despite genetic similarities between man and other anthropoids, the cognitive
      abilities of man are distinct. Inaccessible and concealed external female
      genitals are one of the morphological characteristics distinguishing humans from
      other higher primates. External female sexual organs in subhuman primates are
      visible and accessible in the habitual quadrupedal and occasional bipedal
      posture, whereas these organs in the human female are inaccessible and concealed
      in any posture. A prospective consequence of gradual bipedalism of hominids
      during evolution was a shifting of the external female genitals in an anterior
      direction. In the completely bipedal Homo sapiens, this resulted in the vulvo
      cryptic phenomenon, i.e. concealed female genitals in humans. The unique
      morphology of the human female pelvis served as an obstacle to easy access of the
      male in the process of copulation, necessitating the female's conscious decision
      for sexual intercourse. This circumstance might have created a psychological
      basis for female propellant psychosexual manipulation of the male as a natural
      consequence. Also, through the process of positive selection it could have formed
      a basis for linking reproductive success with the development of cognitive and
      emotional capacities. Female consent to copulation is a conscious and complex act
      that would be impossible without the involvement of highly developed emotional
      cognitive and memoric brain systems. Thus the extraordinary evolutionary strategy
      might imply a teleological link between concealed female genitals and the
      emotional-cognitive characteristics of man, creating a permanent promoter of
      further development of emotional and cognitive brain systems with an impact on
      all domains of everyday life.

PMID- 16641868
TI  - Alcohol-, nicotine-, and cocaine-evoked release of morphine from invertebrate
      ganglia: model system for screening drugs of abuse.
AB  - BACKGROUND: Invertebrates express regulatory receptors, transporters, and
      channels responsive to established drugs of abuse, many of which mediate their
      effects through catecholamine pathways. We hypothesized that invertebrate neural
      systems may serve as models by which to evaluate the interactive pharmacological
      effects of these agents. MATERIAL AND METHODS: Ex vivo pharmacological trials
      determined the effects of saturating levels of ethanol on morphine levels in
      pooled Mytilus edulis ganglia via HPLC coupled to electrochemical detection
      and/or HPLC/RIA analyses. Additional trials evaluated the ability of ethanol,
      nicotine, and cocaine, to promote evoked release of 125I-labeled morphine from
      neural tissues, because intrinsically low levels of morphine did not allow direct
      quantification of its release. RESULTS: Incubation of pooled M. edulis pedal
      ganglia with 200 mM ethanol (approximately 1% ethanol v/v) resulted in a two-fold
      increase in morphine concentration at 15 min, return to baseline at 30 min, and a
      50% decrease in morphine concentration at 60 min. Separate incubations of pooled
      M. edulis pedal ganglia and H. americanus nerve cord with ethanol, cocaine, and
      nicotine resulted in a statistically significant enhancement of 125I-trace
      labeled morphine release. CONCLUSIONS: The stimulatory effects of ethanol,
      nicotine, and cocaine on cellular expression and release of endogenous morphine
      suggest convergent mechanisms underlying the reinforcing and addictive properties
      for a variety of drugs of abuse. The evolutionary conservation of L-tyrosine as a
      common precursor to catecholamine and opiate/opioid signaling systems may define
      a functional triad involving endogenous morphine, dopamine, and other classes of
      addictive drugs.

PMID- 16641869
TI  - Ethanol abrogates angiotensin II-stimulated vascular smooth muscle cell growth.
AB  - BACKGROUND: Aberrant vascular smooth muscle cell (VSMC) proliferation is one of
      the etiological factors for hypertension and stroke. Angiotensin II (Ang II) and
      ethanol (EtOH) have been shown to modulate the proliferation of vascular smooth
      muscle cells (VSMCs) individually, but the combined effects of Ang II and EtOH on
      VSMC proliferative activities are unknown. The objective of this study was to
      determine the effects of EtOH, Ang II, and the combination of Ang II and EtOH on
      DNA synthesis, cell number, cyclic AMP (cAMP) production, and Mitogen-Activated
      Protein Kinase (MAPK) or (p44/42) activities in murine primary VSMCs. MATERIAL
      AND METHODS: Cell growth was determined by [3H] thymidine incorporation and
      confirmed by cell counts using a hemacytometer. Cyclic AMP assays were carried
      out using commercially available kits. MAPK activity was determined by
      immunoprecipitation studies using an ELK-1 fusion protein as a substrate.
      RESULTS: Ang II (10 microM) stimulated DNA synthesis by four-fold (P < 0.05),
      cAMP production by 50% (P < 0.05), and MAPK (p44/42) activities by more than
      seven-fold (P < 0.01). In contrast, EtOH (100 mM) had no significant effects on
      DNA synthesis, cell number, and cAMP production. Ethanol exacerbated cAMP
      production by several fold but inhibited MAPK activity and subsequent cell growth
      induced by Ang II. CONCLUSIONS: These results suggest that EtOH elicits a
      regulatory effect on the Ang II signaling pathway.

PMID- 16641870
TI  - Bifenthrin causes neurite retraction in the absence of cell death: a model for
      pesticide associated neurodegeneration.
AB  - BACKGROUND: Bifenthrin is a synthetic pyrethroid insecticide derivative of
      naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is
      considered relatively safe and therefore incorporated as the active ingredient in
      preparations sold over the counter for household use. Recent studies have raised
      concern that chronic exposure to pesticides in the home setting may increase the
      risk for neurodegenerative diseases. To address this concer, in the present
      study, bifenthrin is added to pre-differentiated PC12 and effect of bifenthrin on
      the retraction of existing neurites is observed a model for neurodegeneration.
      MATERIAL/METHODS: PC12 cells were differentiated with nerve growth factor for
      twenty-four hours and then treated with what was determined to be a sublethal
      dose of bifenthrin for up to an additional 48 hours. The percent of cells with
      neurites was assessed at various times before and after nerve growth factor
      treatment. Bifenthrin toxicity was determined using trypan blue exclusion.
      RESULTS: Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1
      x 10(-10) M to 1 x 10(-4) M. Twenty-four hours after nerve growth factor
      treatment, a maximum percent of cells had formed neurites and with a treatment of
      1 x 10(-5) M bifenthrin, approximately 80% of these neurites retracted in within
      12 additional hours and almost all neurites had retracted within 48 hours. Trypan
      exclusion showed that these cells were viable. CONCLUSIONS: These data show that
      bifenthrin can stimulate the retraction of neurites in the absence of frank
      toxicity.

PMID- 16641871
TI  - Differences in cytochrome P450 2C19 (CYP2C19) expression in adjacent normal and
      tumor tissues in Chinese cancer patients.
AB  - BACKGROUND: Cytochrome P450 2C19 (CYP2C19) exhibits polymorphic expression in
      humans and deficiencies in its expression have been associated with a number of
      different cancers. Our aim was to determine if CYP2C19 mRNA and CYP2C19 enzyme
      protein expression differed between various tumors and normal tissue adjacent to
      the tumor tissue in Han Chinese cancer patients. MATERIALS AND METHODS: The level
      of CYP2C19 mRNA expression was examined in tumor and adjacent normal tissue from
      liver, colon, stomach, breast, esophagus, lung, uterus, brain, pancreas, ovary,
      kidney, and several cell lines by semi-quantitative RT-PCR Western immunoblots
      were also used to qualitatively assess CYP2C19 protein in the above tissues and
      cell lines. RESULTS: CYP2C19 mRNA was found only in normal livers, hepatic
      carcinomas, and hepatocarcinoma cell lines. The CYP2C19 mRNA was expressed at
      significantly higher levels in hepatocellular carcinomas (x +/- s: 3.72 +/- 1.21,
      n = 14) than in adjacent normal liver tissue (x +/- s: 1.79 +/- 0.33, n = 14, p =
      0.000). CYP2C19 protein was also detected in hepatocarcinoma tissues, adjacent
      normal tissues, and the hepatocarcinoma cell lines HepG2, HepGA, and 7721 based
      on Western blotting methods. These results are in accordance with observations
      employing RT-PCR. CONCLUSIONS: CYP2C19 mRNA expression is highest in
      hepatocarcinoma tissue, moderate in adjacent normal liver tissue, and absent in
      other cancer tissues and their adjacent normal tissues. The significantly
      elevated expression of CYP2C19 mRNA in hepatocarcinoma indicates an association
      between the occurrence of hepatocarcinoma and the expression and/or turnover of
      CYP2C19 mRNA.

PMID- 16641872
TI  - The effect of preservatives on the sterility of microorganisms introduced into
      different fruit juices.
AB  - BACKGROUND: The aim of this study was to investigate the degree of sterility of
      some fruit juices post manufacture and to determine how effective the
      preservatives in them aid the killing of some microorganisms introduced into
      them. MATERIAL/METHODS: Blackcurrant/raspberry, apple, guava, orange, mango, and
      mixed fruits were each checked for sterility by inoculating 100 microl separately
      in tryptone soy broth, Robertson's cooked meat, and Sabouraud broth and
      incubating for growth for 72 hours at 37 degrees C. Twenty-milliliter aliquots of
      each juice were subsequently kept in a 37 degrees C water bath and inoculated
      separately with S. aureus, P. aeruginosa, E. coli, and C. albicans. At
      predetermined time intervals, a 1:250 dilution of each juice with the individual
      organism was made and the dilutions were plated on blood and Sabouraud plates for
      viable counts. Each 1:250 dilution was then incubated along with the plates. The
      pH of each undiluted juice was determined. RESULT: All the juices were found to
      be sterile. The growth inhibition exhibited by each juice was bactericidal or
      bacteriostatic, fungicidal or fungistatic, depending on the type of juice. The
      p[H of the juices varied from 2.53-3.75. CONCLUSIONS: We found the juices to be
      bacteriologically free of organisms associated with food infection. Though the
      juices were sterile, they could allow the survival of some bacteria and yeasts if
      these gained access into them. We found the orange, blackcurrant/raspberry, and
      mango juices to be bactericidal and fungicidal, while pineapple, mixed fruit, and
      guava were fungistatic, though with varying bactericidal activities.

PMID- 16641873
TI  - The effect of caffeic acid phenethyl ester on short-term acute myocardial
      ischemia.
AB  - BACKGROUND: We previously showed that caffeic acid phenethyl ester (CAPE)
      attenuated NO production, reduced apoptosis, diminished serum CK and AST
      activities, and is cardio-protective in rat heart subjected to
      ischemia/reperfusion (I/R). We now studied the short-term cardio-protective
      effect of CAPE in an I/R rat heart model. MATERIAL/METHODS: Wistar rats were
      divided into four groups: (i) sham-operated, (ii) I/R, (iii) I/R+CAPE, and (iv)
      I/R+glutathione. CAPE (10 micromol/kg) was infused i.v. 10 min before occlusion
      of the left anterior descending coronary artery (8 min) followed by reperfusion
      (8 min). RESULTS: SOD (p < 0.010) and CAT (p < 0.014) activities were increased
      and GSH-Px (p < 0.019) activity decreased in the I/R group in cardiac tissues
      compared with the sham-operated group. There were no effects of CAPE on
      antioxidant enzyme activities after I/R. Glutathione administration led to
      decreased SOD activity (p < 0.024) and increased GSH-Px (p < 0.014) activity
      after I/R. The most prominent effects of CAPE were seen in XO and ADA activities,
      which were increased after I/R compared with the sham-operated group (p < 0.029
      and p < 0.001, respectively). When CAPE was administered, XO and ADA activities
      were decreased compared with the I/R group (p < 0.045 and p < 0.001). ADA
      activity was also decreased in the I/R+glutathione group compared with the I/R
      group. No differences in basal heart rate or systolic or diastolic pressure were
      noted among the experimental groups. CONCLUSIONS: This study demonstrates that
      CAPE exerts cardio-protective effects in short-term I/R of rat heart. This
      protective effect may be mediated by a combination of decreased XO activity and
      direct antioxidant effects.

PMID- 16641874
TI  - Brain natriuretic peptide is a reliable indicator of ventilatory abnormalities
      during cardiopulmonary exercise test in heart failure patients.
AB  - BACKGROUND: Whether brain natriuretic peptide (BNP), a neurohormone marker of
      ventricular dysfunction, correlates with an enhanced ventilatory response (EVR)
      during cardiopulmonary exercise test, a well-known predictor of prognosis, in
      systolic heart failure (HF) is currently unknown. MATERIAL/METHODS: Resting BNP
      was measured in 134 consecutive stable outpatients aged 69 +/- 11 years with mild
      to moderate HF and LV ejection fraction (LVEF) < 40% who performed a maximal
      exercise test. EVR was assessed as the slope of the relation between minute
      ventilation and carbon dioxide production (VE/VCO2 slope) > or = 35. RESULTS:
      LVEF averaged 33 +/- 7%, BNP 350 +/- 396 pg/ml, and the VE/VCO2 slope 36 +/- 8.
      Fifty-six of 123 patients (45%) had EVR. BNP correlated with VE/VCO2 slope (r =
      0.453; p < 0.01). By multivariate logistic regression, plasma BNP was the only
      independent predictor of EVR (RR: 1.004 per unit increment, 95% CI: 1.002-1.006,
      p < 0.0001). A BNP > or = 160 pg/ml had 86% sensitivity, 67% specificity, and 76%
      overall accuracy for the prediction of EVR (chi square: 37.4, RR 12.2, 95% CI:
      4.96-30.3, p < 0.0001, AUC 0.815 (95%CI. 0.738-0.892)). CONCLUSIONS: In systolic
      HF, plasma BNP is related to an enhanced ventilatory response to exercise and
      offers a simple and reliable alternative to the cardiopulmonary exercise test in
      patients with inability or contraindications to exercise.

PMID- 16641875
TI  - A 10-week Tai-Chi program improved the blood pressure, lipid profile and SF-36
      scores in Hong Kong Chinese women.
AB  - BACKGROUND: Physical activity is associated with a better longevity and reduced
      morbidity. In addition, exercise has a mood-elevating effect, which improves self
      esteem. Tai-Chi is a traditional Chinese aerobic exercise. We aimed to assess the
      short-term effects of Tai-Chi on the clinical parameters and health-related
      quality of life (QOL) in Hong Kong Chinese. MATERIAL/METHODS: Twenty Chinese
      healthy female subjects were recruited. There were 2 Tai-Chi sessions per week
      for 10 weeks. Each session lasted for one hour. Health-related QOL was assessed
      with SF-36 questionnaire. RESULTS: Of the 20 subjects, their mean age was 40.8 +/
      5.9 years (median 42.5 years, range 30-50 years). At the end of the study,
      systolic blood pressure, total cholesterol and low-density lipoprotein
      cholesterol levels significantly reduced (114 +/- 9 to 108 +/- 9 mmHg, p = 0.012;
      4.7 +/- 0.8 to 4.4 +/- 0.5 mmol/L, p = 0.020 and 2.7 +/- 0.6 to 2.2 +/- 0.5
      mmol/L, p = 0.001, respectively). Among all SF-36 items, Vitality and Mental
      Health significantly improved after the 10-week Tai-Chi program (64.9 +/- 8.1 to
      68.4 +/- 6.6, p = 0.038 and 64.4 +/- 6.9 to 69.1 +/- 1.4, p = 0.003,
      respectively). CONCLUSIONS: A 10-week Tai-Chi exercise program improved systolic
      blood pressure, lipid profiles and some of the parameters of health-related QOL
      in Hong Kong Chinese women. Tai-Chi is likely to be a useful choice of physical
      activity. We need a larger study that covers a wider range of populations to
      confirm our results.

PMID- 16641876
TI  - Does music exposure during chemotherapy improve quality of life in early breast
      cancer patients? A pilot study.
AB  - BACKGROUND: Adjuvant chemotherapy is associated with poor quality of life (qol)
      in breast cancer patients. We tested the effect of listening to music during
      chemotherapy on quality of life in these patients. MATERIAL/METHODS: We tested in
      a prospective cohort the changes in qol scores as assessed by European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ-C30), and the influence of listening to non-preferred music at the
      chemotherapy unit on these parameters in a mixed linear model by repeated
      measures analysis of variance (RMANOVA). RESULTS: For the whole cohort, musical
      intervention was not associated with a change in any dimension of quality of
      life. However; the music effect significantly interacted with patient age;
      patients > 45 years old had improved insomnia and appetite loss scores after
      musical intervention (F = 6.76, P = 0.019 and F = 11.22, P = 0.004,
      respectively). CONCLUSIONS: Our results show that brief, non-preferred music
      exposure at the time of chemotherapy administration does not improve quality of
      life in patients with early breast cancer. Nonetheless, there is still a
      possibility that a subgroup will benefit from this approach as suggested by the
      interaction of the music effect with patient age.

PMID- 16641877
TI  - Determination of the incidence and severity of hoarseness after cardiac surgery.
AB  - BACKGROUND: The aim of the study was to determine the incidence and severity of
      hoarseness and vocal cord dysfunction in 200 patients undergoing open heart
      surgery in Shiraz-Iran. MATERIAL/METHODS: This study involved prospective
      evaluation of 200 patients who underwent open heart surgery during the year 2003
      in Shiraz University hospitals. All patients received the same standard
      anesthetic technique. In post-operative course, all patients were electively
      ventilated for variable periods depending on several factors, at least until the
      morning after surgery. All patients underwent direct laryngoscopy immediately
      after extubation by the otolaryngologist, and the existence and grade of
      hoarseness was evaluated on a four-point scale 6 and 12 hours after extubation.
      RESULTS: Two hundred patients, 64.5% male and 35.5% female, with a mean age of
      56.7 (S.D. = 5.2) were evaluated. CABG was performed most frequently and the mean
      duration of cold perfusion was 122 minutes (S.D. = 15). CVP insertion,
      endotracheal intubation, sternotomy, and hypothermia were performed in all
      patients. Hoarseness was found to be present in 17% of patients; all but one were
      rated to be grade one on the four-point scale. However, laryngoscopy did not
      reveal anything specific. CONCLUSIONS: The incidence of hoarseness in this study
      was 17%; similar series reported as high as 32%. Vocal cord dysfunction never
      occurred in our study and hoarseness probably resulted from intubation trauma.
      Although we found no case of nerve injury and cord dysfunction, vocal cord palsy
      as a rare cause of respiratory insufficiency in chest and neck surgeries must
      never be overlooked.

PMID- 16641878
TI  - Urinary activities of cathepsin B, N-acetyl-beta-D-glucosaminidase, and
      albuminuria in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The proximal kidney tubule contains a large number of lysosomes
      involved in the breakdown of intracellular as well as reabsorbed proteins. When
      tubular protein reabsorption is overburdened or when there is tubular cell
      damage, higher urinary excretion of lysosomal enzymes, e.g. cathepsins and N
      acetyl-beta-D-glucosaminidase (NAG), can be found. We compared urinary cathepsin
      B (CB) activity with NAG in diabetic patients. MATERIAL/METHODS: Using
      fluorogenic substrates, urinary and plasma CB and NAG activities in 130 type 2
      diabetic patients with varying stages of albuminuria and 42 control subjects were
      determined. Early morning urine samples were used. RESULTS: In the patients, only
      higher values of plasma NAG were found. In urine, CB and NAG activities increased
      progressively from normoalbuminuria, through microalbuminuria to macroalbuminuria
      group. The normoalbuminuria group had both enzyme activities higher than healthy
      controls. Urine CB activity in the patients also increased gradually to tertiles
      of urinary NAG. Only urinary CB activity was significantly associated with
      glycemic state. The correlation was stronger in the patients with poor glycemic
      control. The plasma/urine ratios for both CB and NAG decreased in the patients
      compared with controls. CONCLUSIONS: Determination of urinary CB activity might
      be useful as a non-invasive surrogate marker of incipient nephropathy.

PMID- 16641879
TI  - Interleukin-8 in the blood serum of patients with alcoholic liver disease.
AB  - BACKGROUND: The influence of the immune system on the development of alcoholic
      liver disease has recently been the object of attention. However, the connection
      between alcohol consumption, altered immune response, and development of changes
      in the liver has not been fully explained. The aim of the present study was to
      evaluate serum IL-8 concentration in patients with chronic alcoholic liver
      disease. MATERIAL/METHODS: 85 patients with different types of ALD and 35 healthy
      subjects were enrolled in the study. Serum IL-8 concentration was evaluated with
      the ELISA immunoenzymatic method. IL-8 in liver tissue was measured by the
      indirect immunofluorescence method. RESULTS: There was a significant correlation
      between IL-8 concentration and AST, ALP, GGT, total bilirubin and albumin levels
      in blood serum. A significantly higher concentration of IL-8 was seen in all the
      groups of ALD patients. The highest values were found in patients with chronic
      alcoholic hepatitis, and the lowest in those with fatty liver. Significantly
      higher values were found in patients with ascites or encephalopathy in comparison
      to those without any features of portal hypertension and/or insufficiency of the
      liver cells. A high concentration of the tested cytokine is a disadvantageous
      prognostic factor in patients with ALD. CONCLUSIONS: IL-8 appears to be an
      important factor in liver pathology in patients with ALD, especially in the
      development of the inflammatory process.

PMID- 16641880
TI  - Analysis of survival factors in patients with advanced-stage gastric
      adenocarcinoma.
AB  - BACKGROUND: Prognosis in patients with gastric cancer is determined by the tumor
      itself, as well as certain patient-related factors. MATERIAL/METHODS: In this
      study, 138 patients with high-grade gastric adenocarcinoma who were admitted to
      our hospital between September 1999 and April 2002 were retrospectively evaluated
      in terms of the effects of clinicopathological parameters and treatment
      approaches on survival by single and multiple variable analyses. Patients
      histopathologically diagnosed as having gastric adenocarcinomas with stage IV M0
      (without distant organ metastasis) or stage IV M1, (with distant organ
      metastasis) were included in the study. RESULTS: Overall median survival time was
      3.1 months and three-year survival rate was 8%. With single variable analysis,
      body mass index (BMI), clinical stage, surgery, type of surgery, and serum level
      of albumin were significant prognostic factors related to overall median survival
      time. Gender, clinical stage, surgery, type of surgery, hemoglobin concentration,
      and serum level of albumin were found to be significant prognostic factors
      related to survival without progression (p < 0.05). No surgical treatment,
      palliative surgery (compared with radical surgery), and BMI below 20 were found
      to be the statistically significant poor prognostic factors related to survival
      in multiple variable analysis. In terms of both overall survival and survival
      without progression, performing surgery or not was statistically the most
      significant independent prognostic factor. CONCLUSIONS: No surgical treatment,
      palliative surgery instead of radical surgery, and BMI below 20 on first
      admission were determined as poor prognostic factors related to survival in
      patients with high-grade gastric adenocarcinoma.

PMID- 16641881
TI  - Multi-systemic methicillin resistant Staphylococcus aureus (MRSA) community
      acquired infection.
AB  - BACKGROUND: An alarming increase of the incidence of community-acquired
      infections due to methicillin resistant Staphylococcus aureus (MRSA) has been
      noted in several countries during the recent years. CASE REPORT: We present the
      case of a 64-year-old male who complained of fever, shortness of breath,
      productive cough, and mild low back pain. The patient was diagnosed to have
      severe community-acquired pneumonia caused by methicillin resistant
      Staphylococcus aureus. Due to the severity of his respiratory symptoms and the
      history of back injury, the mild low back pain did not receive the appropriate
      attention. It became clear later that the back pain was caused by an extra
      pulmonary focus of the MRSA infection. CONCLUSIONS: Staphylococcus aureus has
      been reported to be the cause of considerably different proportions of patients
      with community-acquired pneumonia in studies from various parts of the world. Our
      case emphasizes the occasionally multi-systemic manifestations of community
      acquired MRSA infections and the difficulties in their control.

PMID- 16641882
TI  - Urachal fistula presenting as umbilical sepsis: a rare case in an adult male.
AB  - BACKGROUND: Urachal anomalies are rare normally presenting during childhood. They
      are difficult to diagnose and surgical treatment is always needed to prevent
      recurrence. CASE REPORT: A 28 year old male presented with a red tender umbilical
      swelling that was confused with an umbilical hernia. The correct diagnosis of a
      urachal fistula was reached after performing a CT scan. The patient was initially
      treated with oral antibiotics and complete surgical excision of the fistulous
      tract was carried out at a later stage after controlling the infection.
      CONCLUSIONS: Staged resection is the treatment of choice in urachal anomalies
      associated with sepsis. Surgical excision of the urachal remnant is necessary to
      prevent recurrence.

PMID- 16641883
TI  - Integrating theories of the etiology of Crohn's disease on the etiology of
      Crohn's disease: questioning the hypotheses. William M. Chamberlin, Saleh A.
      Naser Med Sci Monit, 2006; 12(2): RA27-33.

PMID- 16641884
TI  - Pharmacogenetics of antipsychotic-induced weight gain.

PMID- 16641885
TI  - Assessment of the corneal endothelium in acute ultraviolet keratitis.
AB  - BACKGROUND: The purpose of this prospective case-control study was to investigate
      whether exposure to ultraviolet (UV) light produces detectable damage to the
      corneal endothelium in patients presenting with acute UV keratitis.
      MATERIAL/METHODS: Non-contact specular microscopy was performed on 20 consecutive
      patients who presented to our clinic from July 2000 to July 2002 with acute UV
      keratitis and similarly on 20 age-matched healthy controls. Both the coefficient
      of variation in mean cell size (CV) and the mean cell density (CD) were compared
      in these two groups using the Student t-test. RESULTS: Mean age was 28.6 years in
      the study group and 28.4 years in the control group. The mean CD in the patient
      group was 2609.6 (SD = 103.47) and in the control group 2632.87 (SD = 117.05). No
      statistically significant difference was found between the mean CDs in these two
      groups (p = 0.93). The mean CV in the patient group was 46.7 (SD = 4.40) and in
      the control group 45.4 (SD = 5.60). Similarly, there was no statistically
      significant difference between the mean CVs in these two groups (p = 0.85).
      CONCLUSIONS: UV light exposure does not seem to have a direct immediate effect on
      the corneal endothelium in humans with acute UV keratitis. Whether UV light
      produces cumulative and/or longer-term damage requires further studies with a
      larger number of patients and a longer follow-up time.

PMID- 16641886
TI  - Choosing incentives to stimulate tuberculosis treatment compliance in a poor
      county in Rio de Janeiro state, Brazil.
AB  - BACKGROUND: Tuberculosis (TB) treatment default is a major constraint of TB
      control, resulting in continued disease transmission and possibly the emergence
      of multidrug resistance. Marginalized populations may abandon treatment before
      being cured. The objective of this study was to evaluate the socioeconomic status
      (SES) of TB patients and identify potential incentives for improving treatment
      compliance by SES. MATERIAL AND METHODS: A cross-sectional survey was conducted
      in a public health unit in Duque de Caxias, a county with one of the lowest per
      capita incomes in Rio de Janeiro state. From November 2003 to March 2004, 305 TB
      patients answered an anonymous questionnaire on socio-demographic aspects,
      household items and family income, history of previous treatment default, and on
      incentives for improving treatment adherence. Incentives were classified as
      economic, administrative, health service support, and habits, and scored as
      fundamental (3), important (2), desirable (1), or irrelevant (0). RESULTS: Health
      service support incentives had the highest scores overall. The aggregate economic
      incentive score correlated with SES (r = -0.191, p = 0.001). Among the 20%
      poorest patients, 16.7% had a previous history of default vs. 1.6% among the
      wealthiest (p = 0.004). Patients with a history of treatment default were
      significantly more likely to choose health service support incentives than other
      patients (r = -0.263, p = 0.039). CONCLUSIONS: Professional commitment will be
      needed to effect the necessary changes in health service support. Financial
      support for food and transportation subsidies may be required to improve
      treatment compliance among the poorest TB patients, i.e. those most likely to
      have previously defaulted from treatment.

PMID- 16641887
TI  - Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule.
AB  - Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of
      reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production
      and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high
      mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric
      oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa,
      and colonic mucosa in animal models with endotoxemia. These studies suggest that
      pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin
      influences the production of pyruvate by its action on glucose metabolism and
      pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X,
      obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is
      common due to enhanced TNF-alpha production) pyruvate plays a role. This may have
      relevance to the use of glucose-insulin-potassium regimen in these clinical
      conditions, sepsis, and cancer.

PMID- 16641888
TI  - Self-prediction and patient health: influencing health-related behaviors through
      self-prophecy.
AB  - People asked to make a self-prediction about a socially normative behavior are
      significantly more likely (than a comparable control group) to perform the
      behavior in a manner consistent with social norms. Making a behavioral self
      prediction has been demonstrated to increase attendance to a health club,
      consumption of healthy snacks, and commitment to a health and fitness assessment.
      Empirical evidence indicates that this self-prophecy effect is due to dissonance
      based motivation generated by the prediction request. In this article, we present
      self-prediction as a practical and effective tool that health care professionals
      can use to favorably influence a variety of health-related, patient behaviors.
      Previous studies on health behaviors are aggregated using meta-analytical
      techniques to determine the magnitude of self-prediction effects on health
      related behaviors. To account for potential errors of exclusion in our analysis,
      a file drawer analysis is also conducted. Our analysis suggests that self
      prophecy manifests as a small- to medium- effect size when used in the context of
      modifying health-related behaviors. Providing support for the robustness of this
      effect, our file drawer analysis indicated that 270 further studies with null
      results would be needed to negate our conclusions regarding the effect. Based on
      previous research and findings of the current meta-analysis, we are confident
      that health care professionals can effectively employ self-prediction as a method
      for promoting healthier behaviors and lifestyles among their patients.
      Implications for medical practice and allied health fields, as well as areas of
      future research, are identified.

PMID- 16641889
TI  - APOBEC deaminases as cellular antiviral factors: a novel natural host defense
      mechanism.
AB  - The APOBEC (acronym for apolipoprotein B editing catalytic polypeptide) family of
      cytidine deaminases are widely distributed in the biological world and play a
      central role in diverse enzymatic pathways. Members of this family (APOBEC3G and
      APOBEC3F) have been recently shown to be able to restrict HIV-1 replication in
      physiologically relevant target cells (macrophages, lymphocytes), presumably by
      triggering extensive deamination of the viral RNA/DNA replication intermediates.
      This natural antiretroviral host defense mechanism is counteracted by the HIV-1
      protein Vif, which is able to target APOBECs to degrade. The so-called
      "Vif/APOBEC3G paradigm" has been confirmed by a growing literature. However,
      evidence arising from recent studies has expanded this view, showing that the
      replication of other viruses is also restricted by APOBEC family members and
      suggesting antiviral mechanism(s) of action unrelated to the catalytic activity
      of these proteins. Furthermore, evolutionary investigations on primates have
      shown that APOBEC3 gene expansion might be related to an ancient adaptive
      selection to prevent endogenous genetic instability, indicating an additional
      ancient protective role of APOBECs. This article is aimed at broadening the
      current knowledge about the antiviral activity of the APOBEC members and to
      highlight the notion that their role(s) might be more general than previously
      anticipated.

PMID- 16641890
TI  - [Alzheimer's disease as neurodegenerative disorder].
AB  - Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder.
      AD patients are affected by cognitive and memory deterioration. Cerebral
      degeneration, with selective neuronal death induced by extracellular amyloid
      deposits in the form of senile plaques and intracellular neurofibrillary tangles
      composed of helical paired tau protein, is the best-studied pathological event
      related to AD. Presenilins and apolipoprotein E are other neurotoxic agents
      involved in the pathogenesis of AD. A large body evidence has shown that
      permanent activation of glial cells in the brains of AD patients promotes the
      production of excessive quantities of free radicals, nitric oxide, and cytokines
      which could be detrimental to neuronal cells. Damage to the blood-brain barrier
      by inflammatory processes result in the influx of peripheral immune system cells
      and local immune reactions. Inhibition of ROS and NO overproduction as well as
      endogenic regulation of cytokine induction could be of therapeutic importance and
      delay neurodegeneration in AD.

PMID- 16641891
TI  - [Molecular basis of hereditary hemochromatosis].
AB  - Hereditary hemochromatosis (HH) is a genetic metabolic disease characterized by
      increased intestinal iron absorption and progressive iron loading in the cells of
      various organs. Human body iron homeostasis involves a number of complicated
      processes, some of which are not identified yet. Genetic analysis of patients
      affected by HH recently led to the discovery of many novel proteins and
      mechanisms that can influence the uptake, transport, storage, and excretion of
      iron. It also showed that hemochromatosis is a very complex disease and that the
      type of mutation can influence its clinical manifestation. This review presents
      the current knowledge about the mechanisms of iron metabolism and describes the
      types of hereditary hemochromatosis and the mutations which induce the disease.

PMID- 16641892
TI  - [Obesity development associated with viral infections].
AB  - This overview of the significance of viral infections in the development of human
      obesity is presented within context of the commonly recognized obesity risk
      factors, including the personal and public health consequences of obesity in
      various countries. In addition, the results of past and recently published
      studies on the recognition of six taxonomically different viruses which can
      undoubtedly be associated with obesity progression in some species of animals are
      summarized. More attention is focused on the results of preliminary
      epidemiological studies indicating that human infection by the avian adenovirus
      SMAM-1 or the human adenovirus Ad-36 can be objectively related to symptoms,
      prevalence, and complications of obesity in some adult men. Proposed pathogenic
      pathways involved in the observed cases of viral infection-dependent obesity in
      animals and humans are also briefly described. Urgent implementation of high
      throughput diagnostics procedures is advised to extend viral infection-oriented
      modes of prevention, recognition, and therapy of obesity currently available in
      modern societies.

PMID- 16641893
TI  - [The multifaceted effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      organisms, especially dentition changes].
AB  - Dioxins are by products of various technological processes in many branches of
      industry and products of the combustion of chlorine compounds at low
      temperatures. They include polychlorated dibenzo-p-dioxins and dibenzofurans.
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most dangerous to the human
      organism and is a model substance to define the toxicity of particular dioxins in
      mixture. TCDD in small doses exerts a toxic influence on embryos and maturing
      persons. Dioxin exposure to animals and people causes changes in the
      immunological system, fetus failure, and defects in fertility and in internal
      organs and is carcinogenic. Knowledge in this area is rather well documented and
      has expanded. However, there is little information about dioxin's influence on
      dentition development. In this review, recent literature reports and the results
      of own investigations of the general biological effects of dioxins, especially
      for dentition, are presented.

PMID- 16641894
TI  - [The role of reactive oxygen and nitrogen species in calcium and iron homeostasis
      dysregulation in anthracycline cardiotoxicity].
AB  - Anthracyclines are potent anticancer agents which have been used in therapy for
      40 years. However, their activity is very limited due to their cumulative, dose
      dependent, chronic cardiotoxicity. The cardiotoxic effect of anthracyclines may
      lead to irreversible and incurable cardiomyopathy, which impairs quality of live
      and increases the risk of death. The most prominent feature of this cardiac
      disease is diminished ejection fraction of the left ventricle, which leads to
      congestive heart failure. Reactive oxygen species, alcoholic metabolites of
      anthracycline, and cellular calcium homeostasis dysregulation cause chronic
      anthracycline cardiotoxicity. Recently, an important role for reactive nitric
      species and iron homeostasis deregulation was suspected. Some reactive oxygen and
      nitric species might react with one another to produce new, highly toxic
      products. It is suggested that after anthracycline administration, reactive
      oxygen and nitric species affect cellular calcium and iron homeostasis
      deregulation. The possible connection between reactive oxygen and nitric species
      and calcium and iron deregulation is presented in the paper.

PMID- 16641895
TI  - Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell
      lines and tumours.
AB  - The molecular mechanisms that underlie the development of squamous cell skin
      cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to
      compare the differences in cellular gene expression between a series of
      keratinocyte cell that mimic disease progression with the aim of identifying
      genes that may potentially contribute towards squamous cell carcinoma (SCC)
      progression in vivo, and in particular to identify markers that may serve as
      potential therapeutic targets for SCC treatment. Gene expression differences were
      corroborated by polymerase chain reaction and Western blotting. We identified
      Axl, a receptor tyrosine kinase with transforming potential that has also been
      shown to have a role in cell survival, adhesion and chemotaxis, was upregulated
      in vitro in SCC-derived cells compared to premalignant cells. Extending the
      investigation to tumour biopsies showed that the Axl protein was overexpressed in
      vivo in a series of SCCs.

PMID- 16641896
TI  - Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic
      gastric carcinoma.
AB  - The current treatment for metastatic gastric cancer (MGC) consists of cisplatin
      and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based
      regimens are associated with considerable toxicity. We evaluated the efficacy and
      safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in
      MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and
      irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients
      (median age 56 years) received a median of four cycles of docetaxel/irinotecan
      (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a
      partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%).
      At a median follow-up of 15.0 months, the median time to progression was 4.5
      months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8
      10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile
      neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were
      moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was
      manageable by a dose reduction. There was one possible treatment-related death.
      In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in
      MGC, with appropriate dose modification.

PMID- 16641897
TI  - Sentinel node lymphocytes: tumour reactive lymphocytes identified
      intraoperatively for the use in immunotherapy of colon cancer.
AB  - The sentinel node is the first lymph node to receive lymphatic drainage from a
      tumour and is usually the first site of metastases. Today, the sentinel node is
      used for tumour staging. Here, we focus on its immunological role and investigate
      lymphocytic function in sentinel nodes, identified intraoperatively by
      peritumoural dye injection, from 15 patients with colon cancer. Tumour
      infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and
      peripheral blood leukocytes were studied by flow cytometry, proliferation assays
      and interferon-gamma secretion after activation with autologous tumour
      homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the
      proliferation assays, lymphocytes from sentinel nodes proliferated dose
      dependently and secreted interferon-gamma upon stimulation with tumour
      homogenate. The responses were of varying magnitude and tended to be weaker in
      metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched
      source of tumour reactive lymphocytes, and may be useful in future trials of
      adoptive immunotherapy.

PMID- 16641898
TI  - Birth weight and breast cancer risk.
AB  - Exploring whether the positive association between birth weight and breast cancer
      risk differs by other breast cancer risk factors may help inform speculation
      about biological mechanism. In these data, high birth weight was associated with
      breast cancer risk in younger and in more educated women, but was not associated
      overall.

PMID- 16641899
TI  - Genetic instability in lung cancer: concurrent analysis of chromosomal, mini- and
      microsatellite instability and loss of heterozygosity.
AB  - To investigate what kind of genetic instability plays important roles in lung
      carcinogenesis, we analyzed micro- and minisatellite instability, loss of
      heterozygosity (LOH) and chromosome instability in 55 cases of lung cancer,
      including, 10 squamous cell, 5 large cell, and 3 small cell carcinomas, and 37
      adenocarcinomas. Analysis of minisatellite instability, the mechanism of which is
      different from microsatellite instability, has not been reported previously.
      Minisatellite instability was detected in only one case (1/55, 1.8%), and the
      frequency of microsatellite instability was low, being found only in three cases
      (3/55, 5.5%). In contrast, LOH, for at least in one locus, was observed in 27
      cases (49.1%). In adenocarcinomas, the frequency of LOH was higher in poorly
      differentiated compared to more differentiated carcinomas. For chromosome
      instability, a similar correlation between differentiation grade and instability
      was observed in adenocarcinomas. And instability was more common in large cell
      and small cell carcinomas than in adenocarcinomas. Our analysis showed that
      chromosome instability and LOH, rather than mini- and microsatellite instability,
      play significant roles in the development of lung cancer.

PMID- 16641900
TI  - Targeting lymphangiogenesis to prevent tumour metastasis.
AB  - Recent studies involving animal models of cancer and clinicopathological analyses
      of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis)
      in or nearby tumours is associated with the metastatic spread of cancer. The best
      validated molecular signalling system for tumour lymphangiogenesis involves the
      secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that
      induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3)
      localised on the surface of lymphatic endothelial cells. In this review, we
      discuss the evidence supporting a role for this signalling system in the spread
      of cancer and potential approaches for blocking this system to prevent tumour
      metastasis.

PMID- 16641901
TI  - ARF-BP1 as a potential therapeutic target.
AB  - In this review, we discuss the recent identification of ARF-BP1 (also known as
      Mule, UREB1, E3(histone), LASU1, and HectH9). ARF-BP1, a HECT domain-containing
      E3 ubiquitin ligase, interacts with ARF and p53. Its ubiquitin ligase activity is
      inhibited by ARF. Inactivation of ARF-BP1 stabilised p53 and induced apoptosis.
      Notably, inactivation of ARF-BP1 also caused cell growth repression in p53-null
      cells and breast cancer cells with mutant p53. Thus, ARF-BP1 emerges as a novel
      therapeutic target against cancer regardless of p53 status.

PMID- 16641902
TI  - Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification
      and analysis of tumour-related gene methylation.
AB  - Tumour development is characterised by the increased circulating DNA (cirDNA)
      concentration and by tumour-related changes in blood plasma DNA. Concentration of
      cirDNA and methylation of RARbeta2, RASSF1A and HIC-1 gene promoters were
      investigated in cell-free and cell-surface-bound fractions from healthy donors,
      patients with breast cancer, and patients with breast fibroadenoma. Tumour
      development was shown to lead to significant changes in the distribution of
      cirDNA between cell-free and cell-surface-bound fractions. Analysis of RARbeta2
      and RASSF1A methylation in the total cirDNA provides 95% diagnostic coverage in
      breast cancer patients, 60% in patients with benign lesions, and is without false
      positive results in healthy women. Results of the study indicate that methylation
      specific PCR of RARbeta2 and RASSF1A genes based on the total cirDNA combined
      with the quantitative analysis of cirDNA distribution between cell-bound and cell
      free fractions in blood provide the sensitive and accurate detection and
      discrimination of malignant and benign breast tumours.

PMID- 16641903
TI  - Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254
      patients with complete surgical staging.
AB  - A retrospective analysis was performed to evaluate the clinical characteristics
      and prognostic factors in the patients with clear cell carcinoma (CCC) of the
      ovary. After central pathological review and scanning of the medical records of
      nine Japanese institutions between 1992 and 2003, a total of 254 patients with
      CCC of the ovary were enrolled in the present study. Mean age was 52.4 years
      (range 23-73 years). Tumours were 13% (33/254) stage Ia, 36% (92/254) stage Ic,
      13% (33/254) stage II, 30% (80/254) stage III, and 6% (16/254) stage IV. Five
      year progression-free survival and overall survival was 84 and 88% in stage I, 57
      and 70% in stage II, 25 and 33% in stage III and 0 and 0% in stage IV,
      respectively. Retroperitoneal lymph node metastasis was observed in 9% in pT1a
      tumours, 7% in pT1c tumours, 13% in pT2 tumours, and 58% in pT3 tumours,
      respectively. There was no survival benefit according to chemotherapeutic
      differences in the patients who received complete surgical staging procedures and
      conventional chemotherapy. Peritoneal cytological status was an independent
      prognostic factor in stage Ic patients (P=0.03) and only residual tumour diameter
      was an independent prognostic factor in stage III, IV patients (P=0.02). Our
      results suggest that cytoreductive surgery resulting in no residual tumour only
      could improve the prognosis of advanced CCC patients.

PMID- 16641904
TI  - Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel
      for non-small-cell lung cancer.
AB  - This trial aimed to assess the feasibility and tumour control of concurrent
      chemoradiotherapy or radiotherapy alone after docetaxel-based induction
      chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients
      with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy
      with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2).
      Patients without disease progression on day 43 were randomised to radiotherapy (2
      Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once
      weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104
      were evaluable for response. After induction chemotherapy, the overall response
      rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were
      subsequently randomised to local treatment. After randomised therapy, the ORR was
      53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to
      progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and
      14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities
      during induction chemotherapy and randomised therapy were grades 3-4 neutropenia
      and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy
      followed by concurrent docetaxel and thoracic radiotherapy is a feasible
      treatment option, showing good clinical activity and tolerability, for locally
      advanced NSCLC.

PMID- 16641905
TI  - Administration of anti-HER2 antibody after nonmyeloablative allogeneic stem cell
      transplantation in metastatic breast cancer.

PMID- 16641907
TI  - Ras oncogene mutations and survival in patients with lung cancer.

PMID- 16641908
TI  - Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small
      cell lung cancer.
AB  - Telomerase reactivation is a hallmark of human carcinogenesis. Increased
      telomerase activity may result from gene amplification and/or overexpression.
      This study evaluates the prognostic value of hTERT gene amplification and mRNA
      overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens.
      The hTERT gene copy number was assessed by quantitative polymerase chain reaction
      (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by
      fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA
      level was determined by reverse transcription (RT)-qPCR in 130 tumours. In total,
      57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification,
      which was significantly more common (P<0.001) in adenocarcinoma (30 out of 40)
      than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was
      noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell
      than in adenocarcinoma (87 vs 68%, P=0.03). Overexpression was significantly
      associated with amplification (P=0.03), especially in adenocarcinoma. The hTERT
      gene amplification was prognostic for shorter recurrence-free survival (hazard
      ratio=2.16, P=0.03). These data indicate that gene amplification is an important
      mechanism for hTERT overexpression in lung adenocarcinoma and is an independent
      poor prognostic marker for disease-free survival in NSCLC.

PMID- 16641909
TI  - RET rearrangements in post-Chernobyl papillary thyroid carcinomas with a short
      latency analysed by interphase FISH.
AB  - Tissue samples from 13 post-Chernobyl childhood thyroid tumours that occurred
      within a short period of time (4-8 years) after the Chernobyl accident have been
      investigated by interphase FISH analysis for rearrangements of RET. In all, 77%
      of cases showed RET/PTC rearrangements and a distinct intratumoural genetic
      heterogeneity. The data were compared to findings on 32 post-Chernobyl PTCs that
      occurred after a longer period of time (9-12 years) after the accident. In none
      of the cases from either group were 100% of cells positive for RET rearrangement.
      In addition, the pattern of RET-positive cells was different in the two groups
      (short vs longer latency). A significant clustering of aberrant cells could be
      detected in the long-latency subgroup, whereas the aberrant cells were more
      homogeneously distributed among the short-latency tumours. The findings suggest
      that oligoclonal tumour development occurs in post-Chernobyl PTCs. This pattern
      of different clones within the tumour appears to become more discrete in cases
      with longer latencies, suggesting either outgrowth of individual clones or
      development of later subclones with time.

PMID- 16641910
TI  - Vascular endothelial growth factor-A and Poly(A) binding protein-interacting
      protein 2 expression in human head and neck carcinomas: correlation and
      prognostic significance.
AB  - Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an
      important role in tumour angiogenesis and to influence prognosis in many cancers.
      However its prognostic value in head and neck squamous cell carcinomas (HNSCCs)
      remains controversial. Therefore, we investigated the clinical relevance of VEGF
      A expression in HNSCCs and analysed whether its expression was associated with
      PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF
      A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2
      protein levels, quantitatively evaluated in tumour tissue homogenates from 54
      patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A
      expression in HNSCC is correlated to the stage of tumour differentiation
      (P=0.050) and is an independent prognostic factor for progression-free survival
      (P=0.001) and overall survival (P=0.0004). In a pharynx carcinoma cell line, we
      demonstrated by RNA interference that VEGF-A expression is closely controlled by
      PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated
      to PAIP2 protein levels (P=0.0018). Nevertheless, PAIP2 expression is associated
      with neither clinicopathological factors nor patient's survival. Our data suggest
      that, in contrast to PAIP2 protein levels, which are unrelated to tumour
      prognosis, VEGF-A expression could serve as a prognostic marker in head and neck
      cancer and may be helpful for targeted therapies.

PMID- 16641911
TI  - Vinflunine -- an active chemotherapy for treatment of advanced non-small-cell
      lung cancer previously treated with a platinum-based regimen: results of a phase
      II study.
AB  - A multicentre, single-arm, phase II trial designed to determine the efficacy of
      single-agent vinflunine in patients with advanced non-small-cell lung cancer
      (NSCLC) previously treated with a platinum-based regimen. The objectives were to
      assess efficacy in terms of tumour response rate (primary end point), duration of
      response, progression-free survival (PFS) and overall survival (OS), and to
      evaluate the toxicity associated with this treatment. Patients with advanced
      NSCLC with progressive disease having failed prior platinum-based first-line
      treatment for advanced disease. Five responses out of the 63 treated patients
      were documented by WHO criteria and validated by an independent panel review
      (IRP), yielding a response rate of 7.9% (95% CI: 2.6-17.6) in the intent-to-treat
      analysis and 8.3% (95% CI: 2.8-18.4) in the evaluable population. Disease control
      was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of
      response (complete response+partial response), according to modified WHO criteria
      was 7.8 months (95% CI: 4.6-NR). Median PFS was 2.6 months (95% CI: 1.4-3.8), and
      the median survival was 7.0 months (95% CI: 5.8-9.2). Grades 3-4 neutropenia was
      reported in 50% of patients; febrile neutropenia was observed in two patients
      (3.2%); grades 3-4 myalgia and grade 3 constipation were experienced by 10
      (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable,
      non-cumulative and could be prevented with laxative prophylaxis. The encouraging
      results from this phase II study with vinflunine warrant further investigations
      in phase III trials as second- or first-line treatment of advanced non-small-cell
      lung carcinoma, as a single agent or in combination with other active drugs.

PMID- 16641912
TI  - A model of the natural history of screen-detected prostate cancer, and the effect
      of radical treatment on overall survival.
AB  - The lead time and over-detection associated with prostate-specific antigen (PSA)
      screening, and generational improvements in all-cause mortality, make prostate
      cancer outcome studies from the pre-PSA era difficult to interpret in a
      contemporary setting. We developed a competing-risks hazard model to estimate the
      natural history of screen-detected prostate cancer, and the impact of radical
      treatment on overall survival. The model of hazard of mortality was fitted to
      clinical outcome data from the pre-PSA era, and the effects of screening,
      generational mortality improvements and radical treatment were incorporated.
      Sensitivities to the choice of baseline data and values of key parameters were
      assessed. Lead-time estimates in men diagnosed aged 55-59 years were 14.1, 9.3
      and 5.0 years for men with Gleason scores <7, 7 and >7, respectively, assuming
      biennial screening with 100% attendance. Central estimates of 15-year prostate
      cancer mortality for conservative management of screen-detected prostate cancer
      ranged from 0 to 2% for Gleason scores <7, 9 to 31% for Gleason score 7 and 28
      72% for Gleason scores >7. For men aged 55-59 years at diagnosis, the predicted
      absolute 15-year survival benefit from curative treatment was 0, 12 and 26% for
      men with Gleason scores <7, 7 and >7, respectively. Estimates of the survival
      benefit of radical treatment were relatively insensitive to values of key
      parameters. The case for curative treatment, rather than conservative management,
      of screen-detected localised prostate cancer is strongest in men with high-grade
      disease. This conclusion contrasts with current patterns of care.

PMID- 16641913
TI  - The correlation between colorectal cancer rates of proliferation and apoptosis
      and systemic cytokine levels; plus their influence upon survival.
AB  - Colorectal cancer development is associated with a shift in host immunity with
      suppression of the cell-mediated immune system (CMI) and a predominance of
      humoral immunity (HI). Tumour progression is also associated with increased rates
      of cell proliferation and apoptosis. The aim of this study was to investigate
      whether these factors correlate and have an influence upon prognosis. Long-term
      follow-up was performed on 40 patients with colorectal cancer who had levels of
      tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)
      10 measured from stimulated blood cultures before surgery. Their archived tumour
      specimens were analysed to determine a Ki-67-derived proliferation index (PI) and
      a M30-derived apoptosis index (AI). Tumour necrosis factor-alpha levels
      negatively correlated to tumour proliferation (rho=-0.697, P=0.01). Interleukin
      10 levels had a positive correlation with tumour proliferation (rho=0.452,
      P=0.05) and apoptosis (rho=0.587, P=0.01). Patient survival correlates to tumour
      pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI< or =0.6%
      and TNF-alpha levels > or =8148 pg ml(-1) correlate to improved survival
      (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive
      suppression of the CMI-associated cytokine TNF-alpha and to and higher levels of
      IL-10. Survival is dependent upon the histological stage of the tumour, vascular
      invasion, rates of apoptosis and proliferation and systemic immunity which are
      all interconnected.

PMID- 16641914
TI  - Malignant melanoma and bone resorption.
AB  - The cellular and humoral mechanisms accounting for osteolysis in skeletal
      metastases of malignant melanoma are uncertain. Osteoclasts, the specialised
      multinucleated cells that carry out bone resorption, are derived from
      monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs)
      from metastatic (lymph node/skin) melanomas and cultured them in the presence and
      absence of osteoclastogenic cytokines and growth factors. The effect of tumour
      derived fibroblasts and melanoma cells on osteoclast formation and resorption was
      also analysed. Melanoma TAMs (CD14+/CD51-) differentiated into osteoclasts (CD14
      /CD51+) in the presence of receptor activator for nuclear factor kappaB ligand
      (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage
      osteoclast differentiation also occurred via a RANKL-independent pathway when
      TAMs were cultured with tumour necrosis factor-alpha and interleukin (IL)-1alpha.
      RT-PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL
      messenger RNA and the conditioned medium of cultured melanoma fibroblasts was
      found to be capable of inducing osteoclast formation in the absence of RANKL;
      this effect was inhibited by the addition of osteoprotegerin (OPG). We also found
      that cultured human SK-Mel-29 melanoma cells produce a soluble factor that
      induces osteoclast differentiation; this effect was not inhibited by OPG. Our
      findings indicate that TAMs in metastatic melanomas can differentiate into
      osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce
      osteoclast formation by RANKL-dependent and RANKL-independent mechanisms,
      respectively.

PMID- 16641915
TI  - Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder
      cancer.
AB  - Bladder cancer is among the most prevalent malignancies, and is characterised by
      frequent tumour recurrences and localised inflammation, which may promote tissue
      invasion and metastasis. Microarray analysis was used to compare gene expression
      in normal bladder urothelium with that in tumours at different stages of
      progression. The innate immune response gene, interferon-stimulated gene 15 kDa
      (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared
      to normal urothelium. Western blotting revealed a tumour-associated expression of
      ISG15 protein. ISG15 exhibited a stage-associated expression, with significantly
      (P<0.05) higher levels of ISG15 protein in muscle-invasive T2-T4 tumours,
      compared with normal urothelium. Although ISG15 is involved in the primary immune
      response, ISG15 expression did not correlate with bladder inflammation. However,
      immunohistochemical staining revealed expression of ISG15 protein in both cancer
      cells and stromal immune cells. Interestingly, a significant fraction of ISG15
      protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15
      staining was observed in ISG15-positive stromal cells. Taken together, our
      findings identify ISG15 as a novel component of bladder cancer-associated gene
      expression.

PMID- 16641916
TI  - Phase II study of capecitabine and irinotecan combination chemotherapy in
      patients with advanced gastric cancer.
AB  - The present study was conducted to evaluate the efficacy and safety of a
      combination regimen of capecitabine plus irinotecan in patients with advanced
      gastric cancer. Patients with previously untreated metastatic or recurrent,
      measurable gastric cancer received oral capecitabine 1000 mg m(-2) twice daily
      from day 1 to 14 and intravenous irinotecan 100 mg m(-2) on days 1 and 8, based
      on a 3-week cycle. Forty-one patients were enrolled in the current study, among
      whom 38 were assessable for efficacy and 40 assessable for toxicity. Three
      complete responses and 16 partial responses were confirmed, giving an overall
      response rate of 46.3%. At a median follow-up of 269 days, the median time to
      progression and overall survival were 5.1 and 8.6 months, respectively. Grade 3/4
      neutropenia occurred in four patients and grade 3 febrile neutropenia was
      observed in two patients. Grade 3 diarrhoea and grade 2 hand-foot syndrome
      occurred in six patients and eight patients, respectively. The combination of
      capecitabine and irinotecan was found to be well tolerated and effective in
      patients with advanced gastric cancer. Accordingly, this regimen can be regarded
      as one of first-line treatment options for advanced gastric cancer.

PMID- 16641917
TI  - Oxidative stress during peritoneal dialysis: implications in functional and
      structural changes in the membrane.
AB  - Progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration
      failure have been observed in patients on long-term peritoneal dialysis (PD). The
      present study tested the hypothesis that reactive oxygen species (ROS) generated
      by conventional PD solution (PDS) mediate functional and structural alterations
      of peritoneal membrane in vivo. Sprague-Dawley rats were randomized to control,
      PDS, PDS with an antioxidant, and PDS with an angiotensin II (Ang II) receptor
      blocker. Commercial PDS containing 3.86% glucose (20-30 ml) with or without N
      acetylcystein (NAC) 10 mM or losartan 5 mg/kg was administered intraperitoneally
      twice a day for 12 weeks. Control rats received sham injection. Rats treated with
      PDS had significantly lower drain volume and D(4)/D(0) glucose, but higher
      D(4)/P(4) creatinine and increased membrane thickness and endothelial NOS (eNOS)
      expression compared to control rats. Omental transforming growth factor (TGF)
      beta1, vascular endothelial growth factor (VEGF), collagen I, and heat-shock
      protein (hsp) 47 expression and lipid peroxide levels and dialysate VEGF and Ang
      II concentrations were significantly increased in rats treated with PDS compared
      to control. All of these changes were prevented by both NAC and losartan. In
      conclusion, the present study demonstrates that ROS generated by conventional PDS
      are, in large part, responsible for peritoneal fibrosis and membrane
      hyperpermeability. We suggest that antioxidants or Ang II receptor blockers may
      allow better preservation of the structural and functional integrity of the
      peritoneal membrane during long-term PD.

PMID- 16641918
TI  - Environmental exposure to lead and progressive diabetic nephropathy in patients
      with type II diabetes.
AB  - Studies indicate that environmental exposure to lead is associated with reduced
      renal function. Whether lead affects progressive diabetic nephropathy is unclear.
      Eighty-seven patients with type II diabetes and diabetic nephropathy (serum
      creatinine of 1.5-3.9 mg/dl) with normal body lead burden and no lead exposure
      history were observed over a 12-month period. Thirty subjects with high normal
      body lead burdens (80-600 microg) were randomly assigned to a chelation and
      control group. For 3 months, the 15 chelation-group patients underwent lead
      chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly
      until body lead burden fell <60 microg, and the 15 control group subjects
      received a weekly placebo. During the following 12 months, renal function was
      regularly assessed at 3-month intervals. The primary outcome was an elevation of
      serum creatinine to 1.5 times baseline value during the observation period. A
      secondary outcome was temporal changes in renal function following chelation
      therapy. Twenty-six patients achieved the primary outcome. Basal blood lead
      levels and body lead burden were the most important risk factors in predicting
      progressive diabetic nephropathy. Following chelation, the rates of decline in
      glomerular filtration rates in the chelation group and the control group,
      respectively, were 5.0+/-5.7 ml and 11.8+/-7.0 ml/min/year/1.73 m(2) of body
      surface area (P=0.0084) during follow-up, although both groups had similar rates
      of progression of renal function during the 12-month observation period. We
      concluded that low-level environmental lead exposure accelerates progressive
      diabetic nephropathy and lead-chelation therapy can decrease its rate of
      progression.

PMID- 16641919
TI  - An 18-year-old male with hematuria, renal insufficiency, and defective synthesis
      of type IV collagen.

PMID- 16641920
TI  - Subtotal nephrectomy impairs ischemia-induced angiogenesis and hindlimb re
      perfusion in rats.
AB  - Kidney disease is associated with increased cardiovascular morbidity, but
      underlying mechanisms are poorly understood. We tested the hypothesis that
      chronic renal insufficiency impairs angioadaptation in a rat model of hindlimb
      ischemia. Twenty male Sprague-Dawley rats (8 weeks old) underwent subtotal
      nephrectomy (5/6SNX) or sham surgery (each n=10). Ten weeks later, unilateral
      hindlimb ischemia was induced in all animals. Hindlimb perfusion was assessed by
      laser Doppler perfusion imaging and fluorescent microsphere injection studies 2
      weeks after surgery. Ischemia-induced angiogenesis was measured by analyzing
      capillary density using CD31 immunofluorescence. Expression of vascular
      endothelial growth factor (VEGF), its receptors (VEGFRs) and inducible as well as
      endothelial nitric oxide (NO) synthase was measured by real-time reverse
      transcription-polymerase chain reaction. Laser Doppler hindpaw perfusion was
      significantly reduced in 5/6SNX compared to sham-operated animals. Impaired
      hindlimb re-perfusion in 5/6SNX vs control rats was confirmed by fluorescent
      microsphere injection studies (relative perfusion of ischemic vs non-ischemic
      limb: 68.9+/-6.4 vs 92.4+/-3.6%, P=0.005). Ischemic skeletal muscle
      neovascularization increased to a greater extent in sham-operated compared to
      5/6SNX rats (69+/-8 vs 29+/-7%, P<0.05). VEGF and VEGFR-1/2 mRNA expression
      increased in ischemic hindlimbs of control rats, whereas no change or a decrease
      was observed in 5/6SNX. In contrast, inducible and endothelial NO synthase
      expression did not significantly differ between sham and 5/6SNX rats. Chronic
      renal insufficiency impairs angiogenesis and limb perfusion in a rat hindlimb
      ischemia model. Impaired angioadaptation may contribute to the poor prognosis of
      patients with renal failure suffering from peripheral arterial disease.

PMID- 16641921
TI  - Mortality risk for patients receiving hemodiafiltration versus hemodialysis:
      European results from the DOPPS.
AB  - Hemodiafiltration (HDF) is used sporadically for renal replacement therapy in
      Europe but not in the US. Characteristics and outcomes were compared for patients
      receiving HDF versus hemodialysis (HD) in five European countries in the Dialysis
      Outcomes and Practice Patterns Study. The study followed 2165 patients from 1998
      to 2001, stratified into four groups: low- and high-flux HD, and low- and high
      efficiency HDF. Patient characteristics including age, sex, 14 comorbid
      conditions, and time on dialysis were compared between each group using
      multivariate logistic regression. Cox proportional hazards regression assessed
      adjusted differences in mortality risk. Prevalence of HDF ranged from 1.8% in
      Spain to 20.1% in Italy. Compared to low-flux HD, patients receiving low
      efficiency HDF had significantly longer average duration of end-stage renal
      disease (7.0 versus 4.7 years), more history of cancer (15.4 versus 8.7%), and
      lower phosphorus (5.3 versus 5.6 mg/dl); patients receiving high-efficiency HDF
      had significantly more lung disease (15.5 versus 10.2%) and received a higher
      single-pool Kt/V (1.44 versus 1.35). High-efficiency HDF patients had lower crude
      mortality rates than low-flux HD patients. After adjustment, high-efficiency HDF
      patients had a significant 35% lower mortality risk than those receiving low-flux
      HD (relative risk=0.65, P=0.01). These observational results suggest that HDF may
      improve patient survival independently of its higher dialysis dose. Owing to
      possible selection bias, the potential benefits of HDF must be tested by
      controlled clinical trials before recommendations can be made for clinical
      practice.

PMID- 16641922
TI  - Biochemical validation of a rat model for polycystic kidney disease: comparison
      of guanidino compound profile with the human condition.
AB  - Polycystic kidney disease (PKD) accounts for 7-10% of all dialyzed renal
      insufficient patients. Accumulation of specific guanidino compounds (GCs) has
      been related to neurological, cardiovascular, hematological, and immunological
      complications of renal failure. In this study, we investigate whether the PKD/Mhm
      rat model can be used as a biochemical model for human PKD. For the validation of
      the rat model, we performed the first detailed evaluation of the concentrations
      of GCs in serum and urine of patients with PKD in addition to the GC patterns in
      the plasma, urine, and tissues of the PKD/Mhm rat model. The GCs were determined
      after separation on a cation exchange resin and fluorescence detection. The GC
      levels and changes observed in blood and urine of patients with PKD are
      comparable with those found in patients with renal insufficiency due to different
      etiologies. The PKD/Mhm rat model can be used as a biochemical model for human
      PKD as the obvious increases of urea, guanidinosuccinic acid, creatinine,
      guanidine, methylguanidine, and N(G)N(G)-dimethylarginine (symmetrical
      dimethylarginine) seen in blood of oldest heterozygous and younger homozygous PKD
      rats were largely within the same range as those found in the studied human PKD
      population, especially in patients with a glomerular filtration rate below 60
      ml/min/1.73 m(2). The decreased levels of plasma guanidinoacetic acid seen at end
      stage renal disease in homozygous and oldest heterozygous rats were also observed
      in serum of patients with a glomerular filtration rate below 20 ml/min/1.73 m(2).
      The PKD/Mhm rat model has, besides similar disease characteristics with human
      PKD, comparable GC alterations.

PMID- 16641923
TI  - Renal blood flow in experimental septic acute renal failure.
AB  - Reduced renal blood flow (RBF) is considered central to the pathogenesis of
      septic acute renal failure (ARF). However, no controlled experimental studies
      have continuously assessed RBF during the development of severe septic ARF. We
      conducted a sequential animal study in seven female Merino sheep. Flow probes
      were implanted around the pulmonary and left renal arteries. Two weeks later,
      systemic hemodynamics and RBF were monitored continuously during a 48-h control
      period and, after a week, during a 48-h period of hyperdynamic sepsis induced by
      continuous Escherichia coli infusion. Infusion of E. coli induced hyperdynamic
      sepsis with significantly increased cardiac output (3.8+/-0.4 vs 9.8+/-1.1 l/min;
      P<0.05), decreased mean arterial pressure (89.2+/-3.2 vs 64.3+/-5.3 mm Hg;
      P<0.05), and increased total peripheral conductance (42.8+/-3.5 in controls vs
      153.7+/-24.7 ml/min/mm Hg in septic animals; P<0.05). Hyperdynamic sepsis was
      associated with marked renal vasodilatation (renal conductance: 3.0+/-0.7 vs
      11.4+/-3.4 ml/min/mm Hg; P<0.05) and a marked increase in RBF (262.3+/-47.7 vs
      757.4+/-250.1 ml/min; P<0.05). Serum creatinine increased over 48 h (73+/-18 vs
      305+/- micromol/l; P<0.05) whereas creatinine clearance decreased (95.5+/-25.9 vs
      20.1+/-19.3 ml/min; P<0.05). After 24 h, urine output decreased from 1.4 to 0.3
      ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic
      ARF in this setting was associated with a marked increase in RBF and with renal
      vasodilatation.

PMID- 16641924
TI  - Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in
      rat crescentic glomerulonephritis.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that
      maintains the glomerular and peritubular capillary (PTC) network in the kidney.
      The soluble form of the VEGF receptor-1 (soluble fms-like tyrosine kinase 1 (sFlt
      1)) is known to regulate VEGF activity by binding VEGF in the circulation. We
      hypothesized that VEGF may be beneficial for maintaining glomerular filtration
      barrier and vascular network in rats with progressive glomerulonephritis (GN).
      For blockade of VEGF activity in vivo, rats were transfected twice with plasmid
      DNA encoding the murine sFlt-1 gene into femoral muscle 3 days before and 2 weeks
      after the induction of antiglomerular basement membrane antibody-induced GN.
      Inhibition of VEGF with sFlt-1 resulted in massive urinary protein excretion,
      concomitantly with downregulated expression of nephrin in nephritic rats.
      Further, blockade of VEGF induced mild proteinuria in normal rats. Administration
      of sFlt-1 affected neither the infiltration of macrophages nor crescentic
      formation. In contrast, treatment of sFlt-1 accelerated the progression of
      glomerulosclerosis and interstitial fibrosis accompanied with renal dysfunction
      and PTC loss at day 56. VEGF may play a role in maintaining the podocyte function
      as well as renal vasculature, thereby protecting glomeruli and interstitium from
      progressive renal insults.

PMID- 16641925
TI  - The IgA nephropathy treatment dilemma.
AB  - Although IgA nephropathy (IgAN) is the most common form of primary
      glomerulonephritis worldwide, our understanding of the pathogenesis of this
      complex disease remains limited. IgA nephropathy may appear with a variety of
      clinical presentations, a number of different clinical and histopathologic risk
      factors for progressive renal disease, and a very variable course over time.
      Thus, it is not surprising that a single therapeutic treatment plan has not been
      established. Many of the studies dealing with IgAN are retrospective, lack
      statistical significance, or have confounding designs, which hinder their general
      acceptance. Nevertheless, a number of well-designed studies have been performed.
      This paper reviews currently available therapeutic options for IgAN. It attempts
      to address several important questions: Why do we treat patients with IgAN? How
      do we decide which patients should be treated? What are the general treatment
      guidelines for all IgAN patients? What is the role of specific therapy such as
      fish oils, tonsillectomy, and immunosuppression in the treatment of patient with
      IgAN? It also addresses several on-going trials and goals for future therapeutic
      studies for IgAN patients.

PMID- 16641926
TI  - Dual roles of brushite crystals in calcium oxalate crystallization provide
      physicochemical mechanisms underlying renal stone formation.
AB  - Calcium oxalate monohydrate (COM) crystals are the major mineral component of
      most kidney stones, and thus have an important role in chronic human disease.
      However, the physicochemical mechanisms leading to calcium oxalate (CaOx) stone
      disease are only partially defined. As spontaneous precipitation of CaOx is rare
      under renal conditions, an alternative pathway for CaOx crystallization seems
      necessary to resolve this central issue. We performed kinetic studies using the
      dual constant composition method to simultaneously analyze the crystallization of
      COM and brushite, the form of calcium phosphate that is most readily formed in
      the typical slightly acidic urinary milieu. These studies were supported by
      parallel analysis by scanning electron and atomic force microscopy. In these
      studies, mineralization of a thermodynamically stable phase (COM) was induced by
      the presence of brushite, a more readily precipitated inorganic phase.
      Furthermore, once formed, the COM crystals grew at the expense of brushite
      crystals causing the dissolution of the brushite crystals. These studies show
      that brushite may play crucial roles in the formation of COM crystals. The
      definition of these two roles for brushite thereby provides physicochemical
      explanations for the initiation of COM crystallization and also for the relative
      paucity of calcium phosphate detected in the majority of CaOx renal stones.

PMID- 16641927
TI  - Hypertension, Na+/Ca2+ exchanger, and Na+, K+-ATPase.
AB  - Hypertension is the most prevalent risk factor for stroke, myocardial infarction,
      or end-stage renal failure. The critical importance of excess salt intake in the
      pathogenesis of hypertension is widely recognized, but the mechanisms whereby
      salt intake elevates blood pressure have puzzled researchers. Recent studies
      using Na+/Ca2+ exchange inhibitors and genetically engineered mice provide
      evidence that vascular Na+/Ca2+ exchanger type 1 (NCX1) is involved in the
      development of salt-dependent hypertension. Endogenous cardiac glycosides, which
      may contribute to salt-dependent hypertension, seem to be necessary for NCX1
      mediated hypertension. Intriguingly, studies using knock-in mice with modified
      cardiac glycoside binding affinity of Na+,K+-ATPases provide a clear
      demonstration that this cardiac glycoside-binding site plays an important role in
      blood pressure regulation. Taken all together: (1) endogenous cardiac glycosides
      are secreted after high salt intake; (2) these cardiac glycosides inhibit Na+,K+
      ATPase in vascular smooth muscle cells; (3) this inhibition results in the
      elevation of local Na+ on the submembrane area; and (4) this elevation of local
      Na+ facilitates Ca2+ entry through NCX1, resulting in vasoconstriction. This
      proposed pathway may have enabled us to explain how to link dietary salt to
      hypertension.

PMID- 16641928
TI  - Treatment of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is an important cause of progressive kidney disease with
      25-30% of patients developing end-stage renal disease within 20 years of
      diagnosis. There is still no treatment to modify mesangial IgA deposition and
      available treatments are those extrapolated from the management of other patterns
      of chronic glomerulonephritis. There remains no consensus on the use of
      immunosuppressive agents for treatment of progressive IgAN and this is compounded
      by the relative lack in IgAN of randomized controlled trials relevant to current
      clinical practice. Patients with recurrent macroscopic hematuria or isolated
      microscopic hematuria and proteinuria <1 g/24 h require no specific treatment.
      Those with nephrotic syndrome and minimal change on renal biopsy should be
      managed as for minimal change nephropathy. There is no evidence to support the
      use of corticosteroids for nephrotic IgAN outside this group of patients.
      Patients presenting with acute renal failure require evaluation to distinguish
      acute tubular necrosis, which requires supportive therapy only, from crescentic
      IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen
      similar to that for renal small vessel vasculitis is indicated in the absence of
      significant chronic histologic injury. Patients at greatest risk of progressive
      renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced
      glomerular filtration rate at diagnosis. All such patients should be treated to a
      blood pressure of 125/75 mm Hg with dual blockade of the renin-angiotensin system
      with angiotensin-converting enzyme inhibition and angiotensin receptor blockade.
      At present, there is insufficient evidence for the additional use of
      immunosuppressive agents, antiplatelet agents, or anticoagulants.

PMID- 16641929
TI  - BOLD-MRI for the assessment of renal oxygenation in humans: acute effect of
      nephrotoxic xenobiotics.
AB  - Hypoxia of renal medulla is a key factor implicated in the development of drug
      induced renal failure. Drugs are known to influence renal hemodynamics and,
      subsequently, affect renal tissue oxygenation. Changes in renal oxygenation can
      be assessed non-invasively in humans using blood oxygenation level-dependent
      magnetic resonance imaging (BOLD-MRI). This study was designed to test the acute
      effects of administration of specific drugs in healthy human kidney oxygenation
      using BOLD-MRI. Acute changes in renal tissue oxygenation induced by the non
      steroidal anti-inflammatory drug indomethacin, the iodinated radio-contrast media
      (RCM) iopromidum, and the calcineurin inhibitors cyclosporine micro-emulsion (CsA
      ME) and tracrolimus were studied in 30 healthy volunteers. A modified Multi Echo
      Data Image Combination sequence was used to acquire 12 T(2)(*)-weighted images.
      Four coronal slices were selected to cover both kidneys. The mean R(2)(*)
      (1/T(2)(*)) values determined in medulla and cortex showed no significant changes
      induced by indomethacin and tacrolimus administration. CsA-ME decreased medullary
      (P=0.008) and cortical (P=0.004) R(2)(*) values 2 h after ingestion. Iopromidum
      caused a significant increase in medullary R(2)(*) within the first 20 min after
      injection (P<0.001), whereas no relevant changes were observed in renal cortex.
      None of the measurements showed left-right kidney differences. Significant
      differences in renal medullary oxygenation were evidenced between female and male
      subjects (P=0.013). BOLD-MRI was efficient to show effects of specific drugs in
      healthy renal tissue. Cyclosporine increased renal medullary oxygenation 2 h
      after ingestion of a single dose, whereas indomethacin and tacrolimus showed no
      effect on renal oxygenation. Injection of iodinated RCM decreased renal medullary
      oxygenation.

PMID- 16641930
TI  - Definition, evaluation, and classification of renal osteodystrophy: a position
      statement from Kidney Disease: Improving Global Outcomes (KDIGO).
AB  - Disturbances in mineral and bone metabolism are prevalent in chronic kidney
      disease (CKD) and are an important cause of morbidity, decreased quality of life,
      and extraskeletal calcification that have been associated with increased
      cardiovascular mortality. These disturbances have traditionally been termed renal
      osteodystrophy and classified based on bone biopsy. Kidney Disease: Improving
      Global Outcomes (KDIGO) sponsored a Controversies Conference on Renal
      Osteodystrophy to (1) develop a clear, clinically relevant, and internationally
      acceptable definition and classification system, (2) develop a consensus for bone
      biopsy evaluation and classification, and (3) evaluate laboratory and imaging
      markers for the clinical assessment of patients with CKD. It is recommended that
      (1) the term renal osteodystrophy be used exclusively to define alterations in
      bone morphology associated with CKD, which can be further assessed by
      histomorphometry, and the results reported based on a unified classification
      system that includes parameters of turnover, mineralization, and volume, and (2)
      the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader
      clinical syndrome that develops as a systemic disorder of mineral and bone
      metabolism due to CKD, which is manifested by abnormalities in bone and mineral
      metabolism and/or extra-skeletal calcification. The international adoption of
      these recommendations will greatly enhance communication, facilitate clinical
      decision-making, and promote the evolution of evidence-based clinical practice
      guidelines worldwide.

PMID- 16641931
TI  - Leptin induces TGF-beta synthesis through functional leptin receptor expressed by
      human peritoneal mesothelial cell.
AB  - Marked increase in leptin concentration in spent peritoneal dialysate has been
      reported following continuous ambulatory peritoneal dialysis treatment. The
      present study was designed to determine whether functional leptin receptor is
      expressed by human peritoneal mesothelial cells and if so, the possible
      implication in dialysis. Expression of leptin receptors in cultured mesothelial
      cells and omental tissue was examined. The effect of leptin on the production of
      transforming growth factor-beta (TGF-beta) by mesothelial cells in the presence
      or absence of high glucose was determined using in vitro culture model of human
      peritoneal mesothelial cells and adipocytes. The signaling mechanism involved in
      leptin-induced TGF-beta synthesis by mesothelial cells was studied. Both mRNA and
      protein of the full-length leptin receptor are constitutively expressed in
      mesothelial cells. The leptin receptor expression in mesothelial cells was
      upregulated by glucose but not leptin. In adipocytes, glucose increased the mRNA
      expression and synthesis of leptin. The Janus kinase-signal transducers and
      activation (JAK-STAT) signal transduction pathway in mesothelial cells was
      activated by either exogenous or adipocytes-derived leptin. Exogenous leptin
      induced the release of TGF-beta by mesothelial cells. The TGF-beta synthesis
      induced by leptin was amplified by glucose through increased leptin receptor
      expression. Our novel findings reveal that functional leptin receptor is present
      on human peritoneal mesothelial cells. The leptin-induced TGF-beta synthesis in
      mesothelial cells is associated with the expression of leptin receptor and the
      activation of the JAK-STAT signal transduction pathway.

PMID- 16641932
TI  - AIDS, nephrotic-range proteinuria, and renal failure.

PMID- 16641933
TI  - Ten-year prognosis of Puumala hantavirus-induced acute interstitial nephritis.
AB  - Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by
      Puumala hantavirus. Its long-term prognosis is considered favorable. There are,
      however, some reports about subsequent hypertension, glomerular hyperfiltration,
      and proteinuria after previous hantavirus infection. Therefore, we studied 36
      patients 5 and 10 years after acute NE, with 29 seronegative controls. Office
      blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate
      (GFR), and proteinuria were examined. Hypertensive subjects were defined as those
      patients having increased ambulatory or office blood pressure, or receiving
      antihypertensive therapy. Office blood pressure was used to define hypertension
      only if ABP was not determined. At 5 years, the prevalence of hypertension was
      higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the
      difference between the groups was no more significant (39 vs 17%, P=0.098). Five
      years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73
      m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14
      g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more
      differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs
      108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs
      0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE
      is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5
      years disappeared during the longer follow-up. However, the possibility exists
      that NE may predispose some patients to the development of hypertension.

PMID- 16641934
TI  - Time, tumours and telomeres. Meeting on Cancer and Aging.

PMID- 16641935
TI  - Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK)
      potassium channel.
AB  - The pH-sensitive renal potassium channel Kir1.1 is important for K+ homeostasis.
      Disruption of the pH-sensing mechanism causes type II Bartter syndrome. The pH
      sensor is thought to be an anomalously titrated lysine residue (K80) that
      interacts with two arginine residues as part of an 'RKR triad'. We show that a
      Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH
      sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally
      interacts with A177 on transmembrane domain 2 at the 'helix-bundle crossing' and
      controls the ability of pH-dependent conformational changes to induce pore
      closure. Although not required for pH inhibition, K80 is indispensable for the
      coupling of pH gating to the extracellular K+ concentration, explaining its
      conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead
      of interacting with K80, the RKR arginine residues form highly conserved inter-
      and intra-subunit interactions that are important for Kir channel gating and
      influence pH sensitivity indirectly.

PMID- 16641936
TI  - Temperature regulation in depression: functional 5HT1A receptor adaptation
      differentiates antidepressant response.
AB  - Observations in humans and animals have indicated that chronic, but not acute,
      antidepressant treatment (ADT) can desensitize 5-HT1A receptor-mediated
      responses, such as hypothermia. We hypothesized that 5-HT1A desensitization would
      be necessary for an antidepressant response (ADR) to occur. To test this
      hypothesis, we examined 5HT1A-agonist ipsapirone (IPS)-induced hypothermia in 28
      depressed patients being treated with fixed doses of nortriptyline (75 mg) at 3
      day and 3-week treatment points. Decreases in 24-item Hamilton scores (>12) were
      used to dichotomize the response data into ADR groups of 13 responders (ADR+) and
      15 nonresponders (ADR-). A two-way repeated measures analysis of variance
      indicated significant temperature differences in the area under the curve between
      response groups across time from 3-day to 3-week intervals (df=1, 26, F=6.6,
      p<0.02). In comparison to 3 days treatment, at 3 weeks, the ADR+ patients showed
      blunted hypothermic responses to IPS. ADR- did not show this effect, implicating
      ADR+ patients to be less responsive to 5HT1A-receptor stimulation after 3 weeks
      treatment. Similar effects were not found for 5HT1A postsynaptically mediated
      ACTH and cortisol responses. These results indicate that to achieve ADR,
      serotonergic neurotransmission needs to be altered as reflected by the change in
      5-HT1a receptor responsiveness documented herein.

PMID- 16641937
TI  - Galantamine enhances dopaminergic neurotransmission in vivo via allosteric
      potentiation of nicotinic acetylcholine receptors.
AB  - Clinical studies suggest that adjunct galantamine may improve negative and
      cognitive symptoms in schizophrenia. These symptoms may be related to impaired
      dopaminergic function in the prefrontal cortex. Indeed, galantamine has been
      shown to increase dopamine release in vitro. Galantamine is an allosteric
      modulator of nicotinic acetylcholine receptors (nAChRs) and, at higher doses, an
      acetylcholine esterase (AChE) inhibitor. We have previously shown that nicotine,
      through stimulation of nAChRs in the ventral tegmental area (VTA), activates
      midbrain dopamine neurons and, hence, potentiation of these receptors could be an
      additional mechanism by which galantamine can activate dopaminergic pathways.
      Therefore, the effects of galantamine (0.01-1.0 mg/kg s.c.) on dopamine cell
      firing were tested in anaesthetized rats. Already at a low dose, unlikely to
      result in significant AchE inhibition, galantamine increased firing activity of
      dopaminergic cells in the VTA. The effect of galantamine was prevented by the
      nAChR antagonist mecamylamine (1.0 mg/kg s.c.), but not the muscarinic receptor
      antagonist scopolamine (0.1 mg/kg s.c.), and it was not mimicked by the selective
      AChE inhibitor donepezil (1.0 mg/kg s.c.). Our data thus indicate that
      galantamine increases dopaminergic activity through allosteric potentiation of
      nAChRs. Galantamine's effect was also prevented by the alpha7 nAChR antagonist
      methyllycaconitine (6.0 mg/kg i.p.) as well as the N-methyl-D-aspartate
      antagonist CGP39551 (2.5 mg/kg s.c.), indicating a mechanism involving
      presynaptic facilitation of glutamate release. In parallel microdialysis
      experiments, galantamine was found to increase extracellular levels of dopamine
      in the medial prefrontal cortex. These results may have bearing on the
      enhancement of negative and cognitive symptoms in schizophrenia.

PMID- 16641938
TI  - Heroin-induced reinstatement is specific to compulsive heroin use and dissociable
      from heroin reward and sensitization.
AB  - Increased drug availability can precipitate a rapid transition to compulsive drug
      use in both vulnerable humans and laboratory animals. Recent studies have shown
      that despite equivalent levels of psychomotor sensitization, only rats with
      prolonged, but not limited, access to cocaine self-administration respond to the
      priming effects of cocaine on drug seeking, as measured in a within-session
      reinstatement model of drug craving. In this model, drug seeking is first
      extinguished and then reinstated by non-contingent presentations of the drug
      alone in the absence of response-contingent stimuli. Here, we assessed the
      generality of this observation in rats with daily short (1 h, ShA) vs long access
      (6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA
      rats (n=24) increased over time to become excessive compared to heroin intake by
      ShA rats (n=24). After escalation, LgA rats tended to be less sensitive to heroin
      induced locomotion (7.5-30 microg, i.v.) than ShA rats. In contrast, only LgA
      rats, not ShA rats, responded to the priming effects of heroin, as measured by
      the ability of heroin alone (7.5-30 microg, i.v.) to reinstate extinguished drug
      seeking behavior. Finally, during the course of heroin intake escalation, a large
      proportion of LgA rats developed self-injury (mostly targeting the nails and
      digit tips of the forepaws), a negative consequence not seen in ShA rats. This
      study reproduces and extends previous research on compulsive cocaine use by
      showing that heroin-induced reinstatement is also specific to compulsive drug use
      and dissociable from heroin-induced reward and psychomotor sensitization.

PMID- 16641939
TI  - VNS therapy in treatment-resistant depression: clinical evidence and putative
      neurobiological mechanisms.
AB  - Currently available therapeutic interventions for treatment-resistant depression,
      including switch, combination, and augmentation strategies, are less than ideal.
      Observations of mood elevation during vagus nerve stimulation (VNS) therapy for
      pharmacoresistant epilepsy suggested a role for VNS therapy in refractory major
      depression and prompted clinical investigation of this neurostimulation modality.
      The VNS Therapy System has been available for treatment of pharmacoresistant
      epilepsy since 1997 and was approved by the US Food and Drug Administration for
      treatment-resistant depression in July, 2005. The physiology of the vagus nerve,
      mechanics of the VNS Therapy System, and efficacy and safety in pharmacoresistant
      epilepsy are reviewed. Promising results of VNS therapy for treatment-resistant
      depression have been forthcoming from both acute and long-term studies, evidenced
      in part by progressive improvements in depression rating scale scores during the
      1st year of treatment with maintenance of response thereafter. VNS therapy is
      well tolerated in patients with either pharmacoresistant epilepsy or treatment
      resistant depression. As in epilepsy, the mechanisms of VNS therapy of treatment
      resistant depression are incompletely understood. However, evidence from
      neuroimaging and other studies suggests that VNS therapy acts via innervation of
      the nucleus tractus solitarius, with secondary projections to limbic and cortical
      structures that are involved in mood regulation, including brainstem regions that
      contain serotonergic (raphe nucleus) and noradrenergic (locus ceruleus) perikarya
      that project to the forebrain. Mechanisms that mediate the beneficial effects of
      VNS therapy for treatment-resistant depression remain obscure. Suggestions for
      future research directions are described.

PMID- 16641940
TI  - Reciprocal relationships between general (Propofol) anesthesia and circadian time
      in rats.
AB  - Several common postdischarge symptoms, such as sleep disorders, headache,
      drowsiness or general malaise, evoke disturbances of circadian rhythms due to jet
      lag (ie crossing time zones) or shift work rotation. Considering that general
      anesthesia is associated with numerous effects on the central nervous system, we
      hypothesized that it may also act on the circadian timing system. We first
      determined the effects of the circadian timing on general anesthesia. We observed
      that identical doses of propofol showed marked circadian fluctuations in duration
      of effects, with a peak at the middle of the resting period (ie 7 h after lights
      on). Then, we examined the effects of general anesthesia on circadian timing, by
      analysing stable free-running circadian rhythms (ie in constant environmental
      conditions), an experimental approach used widely in circadian biology. Free
      running rats were housed in constant darkness and temperature to assess possible
      phase-shifting effects of propofol anesthesia according to the time of the day.
      When administered around (+/-2 h) the daily rest/activity transition point, a 30
      min propofol anesthesia induced a 1-h phase advance in the free-running rest
      activity rhythm, while anesthesia had no significant resetting effect at other
      times of the day. Anesthesia-induced hypothermia was not correlated with the
      phase-shifting effects of propofol anesthesia. From our results, anesthesia
      itself can reset circadian timing, and acts as a synchronizing cue for the
      circadian clock.

PMID- 16641941
TI  - A glutamate-dopamine interaction in the persistent enhanced response to
      amphetamine in nucleus accumbens core but not shell following a single restraint
      stress.
AB  - The administration of psychostimulant drugs or stress can elicit a sensitized
      response to the stimulating and reinforcing properties of the drug. We previously
      demonstrated that a single restraint stress session enhanced d-amphetamine (d
      AMPH)-induced locomotion the day after the stress session, which lasted up to 8
      days. The present experiments were designed to identify the contribution of major
      dopamine (DA) brain areas in the short- and long-lasting enhancement of d-AMPH
      induced locomotion following a single stress, and to test the involvement of N
      methyl-D-aspartate (NMDA) receptors in that phenomena. To achieve our goal, 24 h
      and 8 days after a 2-h restraint stress session either with or without a NMDA
      receptor blockade, we measured locomotor activity and DA overflow in nucleus
      accumbens (NAcc) core and shell and caudate putamen (CPu) following a d-AMPH
      injection (0.5 mg/kg i.p.). The stimulant effect of d-AMPH on DA overflow was
      enhanced in all nuclei at 24 h after a single stress, while at 8 days the
      enhanced responsiveness was maintained only in the NAcc core. When the rats were
      administered with MK-801 (0.1 mg/kg i.p.) 30 min before restraint stress, the d
      AMPH-induced enhancement on locomotor activity and DA neurotransmission was
      prevented in all studied brain areas at both times. These findings show that a
      glutamate-dopamine link is underlying the short- and long- term d-AMPH-induced
      enhancement on DA and locomotor activity following stress. The persistent
      glutamate-dependent DA enhancement in NAcc core highlights the relevance of this
      region in the long-term proactive effects of stress on vulnerability to drug
      abuse.

PMID- 16641942
TI  - Impact of ambient temperature on hyperthermia induced by (+/-)3,4
      methylenedioxymethamphetamine in rhesus macaques.
AB  - The ambient temperature (T(A)) under which rodents are exposed to (+/-)3,4
      methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the
      body temperature response, and the degree of hypo/hyperthermia generated in
      subjects can modify the severity of lasting brain changes in 'neurotoxicity'
      models. The thermoregulatory effects of MDMA have not been well described in non
      human primates and it is unknown if T(A) has the potential to affect acute
      hyperthermia and therefore other lasting consequences of MDMA. The objective of
      this study was to determine if the temperature alteration produced by MDMA in
      nonhuman primates depends on T(A) as it does in rats and mice. Body temperature
      and spontaneous home cage activity were monitored continuously in six male rhesus
      monkeys via radiotelemetry. The subjects were challenged intramuscularly with
      0.56-2.4 mg/kg (+/-)MDMA under each of three T(A) conditions (18, 24, and 30
      degrees C) in a randomized order. The temperature was significantly elevated
      following injection with all doses of MDMA under each ambient temperature. The
      magnitude of mean temperature change was approximately 1 degrees C in most
      conditions suggesting a closely controlled thermoregulatory response in monkeys
      across a range of doses and ambient temperatures. Activity levels were generally
      suppressed by MDMA; however, a 50% increase over vehicle was observed after 0.56
      MDMA under the 30 degrees C condition. It is concluded that MDMA produces a
      similar degree of hyperthermia in rhesus monkeys across a range of T(A)
      conditions that result in hypothermia or exaggerated hyperthermia in rodents.
      Monkey temperature responses to MDMA appear to be more similar to humans than to
      rodents and therefore the monkey may offer an improved model of effects related
      to MDMA-induced hyperthermia.

PMID- 16641943
TI  - Elevation of glucocorticoids is necessary but not sufficient for the escalation
      of cocaine self-administration by chronic electric footshock stress in rats.
AB  - The examination of cocaine self-administration (SA) by rats under conditions that
      promote escalating patterns of intake should lead to a better understanding of
      factors that contribute to cocaine addiction. This study investigated the ability
      of repeated daily exposure to a stressor, electric footshock (EFS), to escalate
      cocaine SA. Male Sprague-Dawley rats were trained to self-administer cocaine (0.5
      mg/kg/inf, i.v.) by pressing a lever under a FR4 schedule during 2-h sessions
      comprised of four 30-min SA components. Repeated daily EFS consisting of shock
      sequences (3 x 0.6 mA, 100-ms duration, 1-s frequency) delivered under a variable
      time 45-s schedule for 5 min before each of the four SA components across 14 days
      of SA testing produced a significant escalation of cocaine SA. EFS failed to
      escalate food-reinforced lever pressing and did not alter cocaine SA when
      administered either inside or outside of the SA context 4 h after daily SA
      testing. Surgical adrenalectomy along with diurnal corticosterone (CORT)
      replacement prevented EFS-induced escalation without altering SA in the absence
      of EFS, indicating that increases in circulating glucocorticoids were necessary
      for the escalating effects of EFS. Elevation of CORT through repeated daily CORT
      injections (3.0 mg/kg, i.p.) failed to reproduce the effects of repeated daily
      EFS on SA, but restored the escalating effects of EFS in adrenalectomized rats
      with CORT replacement, suggesting that an elevation of glucocorticoids was
      necessary but alone was not sufficient for the escalation of cocaine SA by EFS.

PMID- 16641944
TI  - Effects of antidepressants on the brain/plasma distribution of corticosterone.
AB  - It is well established that hypothalamic-pituitary-adrenal (HPA) axis
      dysregulation, characterized by elevated circulating cortisol concentrations and
      impaired negative feedback inhibition, is associated with affective disorders. As
      normalization of the HPA axis function and mood-stabilizing effects occur
      simultaneously during antidepressant treatment, it is likely that these effects
      are either directly or indirectly dependent. Although data concerning the outward
      transport of glucocorticoids from the brain by P-glycoprotein (Pgp) are
      inconsistent, it has been hypothesized that antidepressants exert their clinical
      activity in parts by inhibiting Pgp, subsequently leading to enhanced brain
      glucocorticoid levels and the normalization of the HPA axis function. Here, we
      report on the effects of different antidepressants (amitriptyline, fluoxetine,
      mirtazapine, St John's wort extract) on the brain/plasma distribution of
      corticosterone in mice after acute and subchronic treatment. The four
      antidepressants exerted different effects on the corticosterone concentration in
      brain and plasma. Changes in corticosterone levels were highly correlated,
      suggesting passive diffusion between both tissues. St John's wort extract and
      fluoxetine elevated brain and plasma corticosterone concentrations after
      subchronic treatment. Mirtazapine and amitriptyline had no effect on
      corticosterone concentration after subchronic treatment, possibly because both
      are also potent antagonists at the 5-HT2 receptor, which mediates HPA axis
      stimulation by serotonergic stimuli. In addition, St John's wort is the only
      antidepressant tested which slightly elevated Pgp protein level in the brain.

PMID- 16641945
TI  - Caspase-3 activation in rat frontal cortex following treatment with typical and
      atypical antipsychotics.
AB  - In schizophrenia, studies indicate that apoptotic susceptibility in cortex may be
      increased. A role for apoptosis in schizophrenia could potentially contribute to
      post-mortem evidence of reduced cortical neuropil and neuroimaging studies
      showing progressive cortical gray matter loss. Interestingly, antipsychotic
      treatment has been associated with higher cortical levels of anti-apoptotic Bcl-2
      protein in rat cortex and preliminary data has suggested a similar association in
      schizophrenia and bipolar disorder. To better understand the effects of
      antipsychotics on apoptotic regulation, rats were administered haloperidol,
      clozapine, quetiapine, or saline daily for 4 weeks. Multiple apoptotic markers,
      including Bcl-2, pro-apoptotic Bax, anti-apoptotic XIAP, and the downstream
      protease caspase-3 were measured in frontal cortex using Western blot. Caspase-3
      activity, activated caspase-3-positive cell number, and DNA/histone fragmentation
      levels were also determined. Western blot showed that immunoreactivity of Bax and
      Bcl-2 bands were unchanged with treatment. However, mean density of the 19 kD
      activated caspase-3 band was 55% higher with haloperidol (p<0.001), 40% higher
      with clozapine (p<0.05), and 48% higher with quetiapine (p<0.01) compared to
      saline control. Specific activity of caspase-3 was also increased across all
      treatments (p<0.0001), while DNA fragmentation rates remained unchanged. These
      data suggest that sub-chronic antipsychotic treatment is associated with non
      lethal caspase-3 activity. The findings do not support a prominent Bcl-2-mediated
      neuroprotective role for antipsychotics. Although the association between
      antipsychotic treatment and increased pro-apoptotic caspase-3 is intriguing,
      further study is needed to understand its potential effects.

PMID- 16641946
TI  - Differential roles of dopamine D1 and D2 receptors in the nucleus accumbens in
      attentional performance on the five-choice serial reaction time task.
AB  - Nucleus accumbens (NAC) dopamine may play a role in attentional and executive
      processes, as it modulates cortico-limbic inputs, including afferents from the
      prefrontal cortex. The present study examined the role of NAC dopamine D1 and D2
      receptors in visual attentional processes and response control in rats as
      assessed in the five-choice serial reaction time task (5CSRT). Rats were trained
      to detect the location of brief (0.5 s) visual targets presented randomly in an
      array of five apertures to receive food reward. They were tested after bilateral
      infusions of a D1 receptor antagonist (SCH 23390) and agonist (SKF 38393) and a
      D2 receptor antagonist (sulpiride) and agonist (quinpirole) into the NAC. While
      intra-NAC SCH 23390 decreased accurate responding and increased response
      omissions, SKF 38393 improved accuracy and decreased omissions at the lowest dose
      (0.1 microg/side). At higher doses, SKF 38393 increased premature 'impulsive'
      responding. Sulpiride impaired the attentional accuracy of responding and slowed
      the latency to collect the earned food reward. By contrast, intra-NAC infusions
      of quinpirole did not significantly affect attentional accuracy, but increased
      perseverative responding. Optimal performance on the 5CSRT depends on both D1 and
      D2 receptors in the NAC, but they modulate different aspects of performance. D1
      receptor agents had more selective effects on attentional accuracy while D2
      receptor stimulation did not affect accuracy or premature responses, but enhanced
      perseverative responding. The data are discussed in terms of the different
      functions of NAC dopamine receptors in the processing of information from its
      different cortico-limbic inputs.

PMID- 16641947
TI  - Baseline neurocognitive deficits in the CATIE schizophrenia trial.
AB  - Neurocognition is moderately to severely impaired in patients with schizophrenia.
      However, the factor structure of the various neurocognitive deficits, the
      relationship with symptoms and other variables, and the minimum amount of testing
      required to determine an adequate composite score has not been determined in
      typical patients with schizophrenia. An 'all-comer' approach to cognition is
      needed, as provided by the baseline assessment of an unprecedented number of
      patients in the CATIE (Clinical Antipsychotic Trials of Intervention
      Effectiveness) schizophrenia trial. From academic sites and treatment providers
      representative of the community, 1493 patients with chronic schizophrenia were
      entered into the study, including those with medical comorbidity and substance
      abuse. Eleven neurocognitive tests were administered, resulting in 24 individual
      scores reduced to nine neurocognitive outcome measures, five domain scores and a
      composite score. Despite minimal screening procedures, 91.2% of patients provided
      meaningful neurocognitive data. Exploratory principal components analysis yielded
      one factor accounting for 45% of the test variance. Confirmatory factor analysis
      showed that a single-factor model comprised of five domain scores was the best
      fit. The correlations among the factors were medium to high, and scores on
      individual factors were very highly correlated with the single composite score.
      Neurocognitive deficits were modestly correlated with negative symptom severity
      (r=0.13-0.27), but correlations with positive symptom severity were near zero
      (r<0.08). Even in an 'all-comer' clinical trial, neurocognitive deficits can be
      assessed in the overwhelming majority of patients, and the severity of impairment
      is similar to meta-analytic estimates. Multiple analyses suggested that a broad
      cognitive deficit characterizes this sample. These deficits are modestly related
      to negative symptoms and essentially independent of positive symptom severity.

PMID- 16641948
TI  - Molecular virology: was the 1918 pandemic caused by a bird flu?
AB  - Taubenberger et al. have sequenced the polymerase genes of the pandemic 'Spanish'
      influenza A virus of 1918, thereby completing the decoding of the genome of this
      virus. The authors conclude from these sequences that the virus jumped from birds
      to humans shortly before the start of the pandemic and that it was not derived
      from earlier viruses by gene shuffling, a process called reassortment. However,
      we believe that their evidence does not convincingly support these conclusions
      and that some of their results even indicate that, on the contrary, the virus
      evolved in mammals before the pandemic began and that it was a reassortant. In
      light of this alternative interpretation, we suggest that the current intense
      surveillance of influenza viruses should be broadened to include mammalian
      sources.

PMID- 16641950
TI  - Molecular virology: was the 1918 flu avian in origin?
AB  - Taubenberger et al. claim that the 1918 influenza virus was derived from an avian
      source and adapted to humans shortly before the pandemic. However, we do not
      believe that this conclusion, which has been widely disseminated in the popular
      press and in scientific journals, is supported by their phylogenetic evidence.

PMID- 16641954
TI  - Bioethics at the bench.

PMID- 16641955
TI  - Making collider endorsement count.

PMID- 16641956
TI  - Machine readability.

PMID- 16641958
TI  - US particle physics fights for survival.

PMID- 16641959
TI  - Shifting constant could shake laws of nature.

PMID- 16641961
TI  - Last hope for river dolphins.

PMID- 16641962
TI  - World Bank defends efforts to curb malaria.

PMID- 16641963
TI  - Flu-vaccine makers toil to boost supply.

PMID- 16641964
TI  - Feel it in your bones.

PMID- 16641966
TI  - Bioethics: dial 'E' for ethics.

PMID- 16641968
TI  - Geophysics: magical mantle tour.

PMID- 16641967
TI  - Archaeology: digital digs.

PMID- 16641969
TI  - Crunch time for New Jersey lab.

PMID- 16641970
TI  - Funding should recognize outcome, not income.

PMID- 16641971
TI  - It's incredible how often we're surprised by findings.

PMID- 16641972
TI  - Everyone listed on Dolly paper met established criteria for authorship.

PMID- 16641977
TI  - Superconductivity: quantum stripe search.

PMID- 16641976
TI  - Language: startling starlings.

PMID- 16641981
TI  - Gene therapy: therapeutic gene causing lymphoma.
AB  - The development of T-cell leukaemia following the otherwise successful treatment
      of three patients with X-linked severe combined immune deficiency (X-SCID) in
      gene-therapy trials using haematopoietic stem cells has led to a re-evaluation of
      this approach. Using a mouse model for gene therapy of X-SCID, we find that the
      corrective therapeutic gene IL2RG itself can act as a contributor to the genesis
      of T-cell lymphomas, with one-third of animals being affected. Gene-therapy
      trials for X-SCID, which have been based on the assumption that IL2RG is
      minimally oncogenic, may therefore pose some risk to patients.

PMID- 16641983
TI  - Cosmology from start to finish.
AB  - Cosmology is undergoing a revolution. With recent precise measurements of the
      cosmic microwave background radiation, large galaxy redshift surveys, better
      measurements of the expansion rate of the Universe and a host of other
      astrophysical observations, there is now a standard, highly constrained
      cosmological model. It is not a cosmology that was predicted. Unidentified dark
      particles dominate the matter content of our Universe, and mysteries surround the
      processes responsible for the accelerated expansion at its earliest moments
      (inflation?) and for its recent acceleration (dark energy?). New measurements
      must address the fundamental questions: what happened at the birth of the
      Universe, and what is its ultimate fate?

PMID- 16641984
TI  - Is our Universe natural?
AB  - It goes without saying that we are stuck with the Universe we have. Nevertheless,
      we would like to go beyond simply describing our observed Universe, and try to
      understand why it is that way rather than some other way. When considering both
      the state in which we find our current Universe, and the laws of physics it
      obeys, we discover features that seem remarkably unnatural to us. Physicists and
      cosmologists have been exploring increasingly ambitious ideas in an attempt to
      explain how surprising aspects of our Universe can arise from simple dynamical
      principles.

PMID- 16641985
TI  - The large-scale structure of the Universe.
AB  - Research over the past 25 years has led to the view that the rich tapestry of
      present-day cosmic structure arose during the first instants of creation, where
      weak ripples were imposed on the otherwise uniform and rapidly expanding
      primordial soup. Over 14 billion years of evolution, these ripples have been
      amplified to enormous proportions by gravitational forces, producing ever-growing
      concentrations of dark matter in which ordinary gases cool, condense and fragment
      to make galaxies. This process can be faithfully mimicked in large computer
      simulations, and tested by observations that probe the history of the Universe
      starting from just 400,000 years after the Big Bang.

PMID- 16641986
TI  - High-redshift galaxy populations.
AB  - We now see many galaxies as they were only 800 million years after the Big Bang,
      and that limit may soon be exceeded when wide-field infrared detectors are widely
      available. Multi-wavelength studies show that there was relatively little star
      formation at very early times and that star formation was at its maximum at about
      half the age of the Universe. A small number of high-redshift objects have been
      found by targeting X-ray and radio sources and most recently, gamma-ray bursts.
      The gamma-ray burst sources may provide a way to reach even higher-redshift
      galaxies in the future, and to probe the first generation of stars.

PMID- 16641987
TI  - Heavy element synthesis in the oldest stars and the early Universe.
AB  - The first stars in the Universe were probably quite different from those born
      today. Composed almost entirely of hydrogen and helium (plus a tiny trace of
      lithium), they lacked the heavier elements that determine the formation and
      evolution of younger stars. Although we cannot observe the very first stars--they
      died long ago in supernovae explosions--they created heavy elements that were
      incorporated into the next generation. Here we describe how observations of heavy
      elements in the oldest surviving stars in our Galaxy's halo help us understand
      the nature of the first stars--those responsible for the chemical enrichment of
      our Galaxy and Universe.

PMID- 16641988
TI  - Structural basis for broad DNA-specificity in integron recombination.
AB  - Lateral DNA transfer--the movement of genetic traits between bacteria--has a
      profound impact on genomic evolution and speciation. The efficiency with which
      bacteria incorporate genetic information reflects their capacity to adapt to
      changing environmental conditions. Integron integrases are proteins that mediate
      site-specific DNA recombination between a proximal primary site (attI) and a
      secondary target site (attC) found within mobile gene cassettes encoding
      resistance or virulence factors. The lack of sequence conservation among attC
      sites has led to the hypothesis that a sequence-independent structural
      recognition determinant must exist within attC. Here we report the crystal
      structure of an integron integrase bound to an attC substrate. The structure
      shows that DNA target site recognition and high-order synaptic assembly are not
      dependent on canonical DNA but on the position of two flipped-out bases that
      interact in cis and in trans with the integrase. These extrahelical bases, one of
      which is required for recombination in vivo, originate from folding of the bottom
      strand of attC owing to its imperfect internal dyad symmetry. The mechanism
      reported here supports a new paradigm for how sequence-degenerate single-stranded
      genetic material is recognized and exchanged between bacteria.

PMID- 16641989
TI  - Origin of the obliquities of the giant planets in mutual interactions in the
      early Solar System.
AB  - The origin of the spin-axis orientations (obliquities) of the giant planets is a
      fundamental issue because if the obliquities resulted from tangential collisions
      with primordial Earth-sized protoplanets, then they are related to the masses of
      the largest planetesimals out of which the planets form. A problem with this
      mechanism, however, is that the orbital planes of regular satellites would
      probably be uncorrelated with the obliquities, contrary to observations.
      Alternatively, they could have come from an external twist that affected the
      orientation of the Solar System plane; but in this model, the outer planets must
      have formed too rapidly, before the event that produced the twist. Moreover, the
      model cannot be quantitatively tested. Here I show that the present obliquities
      of the giant planets were probably achieved when Jupiter and Saturn crossed the
      1:2 orbital resonance during a specific migration process: different migration
      scenarios cannot account for the large observed obliquities. The existence of the
      regular satellites of the giant planets does not represent a problem in this
      model because, although they formed soon after the planetary formation, they can
      follow the slow evolution of the equatorial plane it produces.

PMID- 16641990
TI  - Wave and defect dynamics in nonlinear photonic quasicrystals.
AB  - Quasicrystals are unique structures with long-range order but no periodicity.
      Their properties have intrigued scientists ever since their discovery and initial
      theoretical analysis. The lack of periodicity excludes the possibility of
      describing quasicrystal structures with well-established analytical tools,
      including common notions like Brillouin zones and Bloch's theorem. New and unique
      features such as fractal-like band structures and 'phason' degrees of freedom are
      introduced. In general, it is very difficult to directly observe the evolution of
      electronic waves in solid-state atomic quasicrystals, or the dynamics of the
      structure itself. Here we use optical induction to create two-dimensional
      photonic quasicrystals, whose macroscopic nature allows us to explore wave
      transport phenomena. We demonstrate that light launched at different quasicrystal
      sites travels through the lattice in a way equivalent to quantum tunnelling of
      electrons in a quasiperiodic potential. At high intensity, lattice solitons are
      formed. Finally, we directly observe dislocation dynamics when crystal sites are
      allowed to interact with each other. Our experimental results apply not only to
      photonics, but also to other quasiperiodic systems such as matter waves in
      quasiperiodic traps, generic pattern-forming systems as in parametrically excited
      surface waves, liquid quasicrystals, and the more familiar atomic quasicrystals.

PMID- 16641991
TI  - Electron-phonon coupling reflecting dynamic charge inhomogeneity in copper oxide
      superconductors.
AB  - The attempt to understand copper oxide superconductors is complicated by the
      presence of multiple strong interactions in these systems. Many believe that
      antiferromagnetism is important for superconductivity, but there has been renewed
      interest in the possible role of electron-lattice coupling. The conventional
      superconductor MgB2 has a very strong electron-lattice coupling, involving a
      particular vibrational mode (phonon) that was predicted by standard theory and
      confirmed quantitatively by experiment. Here we present inelastic scattering
      measurements that show a similarly strong anomaly in the Cu-O bond-stretching
      phonon in the copper oxide superconductors La(2-x)Sr(x)CuO4 (with x = 0.07,
      0.15). Conventional theory does not predict such behaviour. The anomaly is
      strongest in La(1.875)Ba(0.125)CuO4 and La(1.48)Nd(0.4)Sr(0.12)CuO4, compounds
      that exhibit spatially modulated charge and magnetic order, often called stripe
      order; it occurs at a wave vector corresponding to the charge order. These
      results suggest that this giant electron-phonon anomaly, which is absent in
      undoped and over-doped non-superconductors, is associated with charge
      inhomogeneity. It follows that electron-phonon coupling may be important to our
      understanding of superconductivity, although its contribution is likely to be
      indirect.

PMID- 16641992
TI  - Dislocation multi-junctions and strain hardening.
AB  - At the microscopic scale, the strength of a crystal derives from the motion,
      multiplication and interaction of distinctive line defects called dislocations.
      First proposed theoretically in 1934 (refs 1-3) to explain low magnitudes of
      crystal strength observed experimentally, the existence of dislocations was
      confirmed two decades later. Much of the research in dislocation physics has
      since focused on dislocation interactions and their role in strain hardening, a
      common phenomenon in which continued deformation increases a crystal's strength.
      The existing theory relates strain hardening to pair-wise dislocation reactions
      in which two intersecting dislocations form junctions that tie the dislocations
      together. Here we report that interactions among three dislocations result in the
      formation of unusual elements of dislocation network topology, termed 'multi
      junctions'. We first predict the existence of multi-junctions using dislocation
      dynamics and atomistic simulations and then confirm their existence by
      transmission electron microscopy experiments in single-crystal molybdenum. In
      large-scale dislocation dynamics simulations, multi-junctions present very
      strong, nearly indestructible, obstacles to dislocation motion and furnish new
      sources for dislocation multiplication, thereby playing an essential role in the
      evolution of dislocation microstructure and strength of deforming crystals.
      Simulation analyses conclude that multi-junctions are responsible for the strong
      orientation dependence of strain hardening in body-centred cubic crystals.

PMID- 16641993
TI  - The twentieth century was the wettest period in northern Pakistan over the past
      millennium.
AB  - Twentieth-century warming could lead to increases in the moisture-holding
      capacity of the atmosphere, altering the hydrological cycle and the
      characteristics of precipitation. Such changes in the global rate and
      distribution of precipitation may have a greater direct effect on human well
      being and ecosystem dynamics than changes in temperature itself. Despite the co
      variability of both of these climate variables, attention in long-term climate
      reconstruction has mainly concentrated on temperature changes. Here we present an
      annually resolved oxygen isotope record from tree-rings, providing a millennial
      scale reconstruction of precipitation variability in the high mountains of
      northern Pakistan. The climatic signal originates mainly from winter
      precipitation, and is robust over ecologically different sites. Centennial-scale
      variations reveal dry conditions at the beginning of the past millennium and
      through the eighteenth and early nineteenth centuries, with precipitation
      increasing during the late nineteenth and the twentieth centuries to yield the
      wettest conditions of the past 1,000 years. Comparison with other long-term
      precipitation reconstructions indicates a large-scale intensification of the
      hydrological cycle coincident with the onset of industrialization and global
      warming, and the unprecedented amplitude argues for a human role.

PMID- 16641994
TI  - Lamprey-like gills in a gnathostome-related Devonian jawless vertebrate.
AB  - So far, the Palaeozoic fossil jawless vertebrates have not provided any direct
      evidence for the organization of the gills, apart from vague impressions-
      supposedly left by gill filaments--on the bony surface of the gill chamber in
      certain armoured forms or 'ostracoderms' (for example, osteostracans and
      heterostracans). The latter are currently regarded as more closely related to the
      living jawed vertebrates (crown gnathostomes) than to the living jawless
      vertebrates (hagfish and lampreys, or cyclostomes). Here we report the first
      direct evidence for the position of the gill filaments--possibly supported by
      gill rays--enclosed by gill pouches in a 370-million year (Myr)-old jawless
      vertebrate, Endeiolepis, from the Late Devonian fossil fish site of Miguasha,
      Quebec, Canada. This extinct jawless fish has much the same gill organization as
      living lampreys, although it possesses an unusually large number of gill pouches-
      a condition unlike that in any extant vertebrates and that raises questions about
      gill development. Endeiolepis is currently regarded as a close relative of
      anaspids, a group of 410-430-Myr-old 'ostracoderms'. Assuming that current
      vertebrate phylogeny is correct, this discovery demonstrates that pouches
      enclosing the gills are primitive for vertebrates, but have been subsequently
      lost in jawed vertebrates.

PMID- 16641995
TI  - Heterotrophic plasticity and resilience in bleached corals.
AB  - Mass coral bleaching events caused by elevated seawater temperatures have
      resulted in extensive coral mortality throughout the tropics over the past few
      decades. With continued global warming, bleaching events are predicted to
      increase in frequency and severity, causing up to 60% coral mortality globally
      within the next few decades. Although some corals are able to recover and to
      survive bleaching, the mechanisms underlying such resilience are poorly
      understood. Here we show that the coral host has a significant role in recovery
      and resilience. Bleached and recovering Montipora capitata (branching) corals met
      more than 100% of their daily metabolic energy requirements by markedly
      increasing their feeding rates and CHAR (per cent contribution of
      heterotrophically acquired carbon to daily animal respiration), whereas Porites
      compressa (branching) and Porites lobata (mounding) corals did not. These
      findings suggest that coral species with high-CHAR capability during bleaching
      and recovery, irrespective of morphology, will be more resilient to bleaching
      events over the long term, could become the dominant coral species on reefs, and
      may help to safeguard affected reefs from potential local and global extinction.

PMID- 16641996
TI  - Rank-related maternal effects of androgens on behaviour in wild spotted hyaenas.
AB  - Within any hierarchical society, an individual's social rank can have profound
      effects on its health and reproductive success, and rank-related variation in
      these traits is often mediated by variation in endocrine function. Maternal
      effects mediated by prenatal hormone exposure are potentially important for non
      genetic inheritance of phenotypic traits related to social rank, and thus for
      shaping individual variation in behaviour and social structure. Here we show that
      androgen concentrations in wild female spotted hyaenas (Crocuta crocuta) are
      higher during late gestation in dominant females than in subordinate females.
      Furthermore, both male and female cubs born to mothers with high concentrations
      of androgens in late pregnancy exhibit higher rates of aggression and mounting
      behaviour than cubs born to mothers with lower androgen concentrations. Both
      behaviours are strongly affected in other mammals by organizational effects of
      androgens, and both have important effects on fitness in hyaenas. Therefore, our
      results suggest that rank-related maternal effects of prenatal androgen exposure
      can adaptively influence offspring phenotype in mammals, as has previously been
      shown to occur in birds. They also suggest an organizational mechanism for the
      development of female dominance and aggressiveness in spotted hyaenas, traits
      that may offset the costs of extreme virilization.

PMID- 16641998
TI  - Recursive syntactic pattern learning by songbirds.
AB  - Humans regularly produce new utterances that are understood by other members of
      the same language community. Linguistic theories account for this ability through
      the use of syntactic rules (or generative grammars) that describe the acceptable
      structure of utterances. The recursive, hierarchical embedding of language units
      (for example, words or phrases within shorter sentences) that is part of the
      ability to construct new utterances minimally requires a 'context-free' grammar
      that is more complex than the 'finite-state' grammars thought sufficient to
      specify the structure of all non-human communication signals. Recent hypotheses
      make the central claim that the capacity for syntactic recursion forms the
      computational core of a uniquely human language faculty. Here we show that
      European starlings (Sturnus vulgaris) accurately recognize acoustic patterns
      defined by a recursive, self-embedding, context-free grammar. They are also able
      to classify new patterns defined by the grammar and reliably exclude agrammatical
      patterns. Thus, the capacity to classify sequences from recursive, centre
      embedded grammars is not uniquely human. This finding opens a new range of
      complex syntactic processing mechanisms to physiological investigation.

PMID- 16641997
TI  - The DNA sequence, annotation and analysis of human chromosome 3.
AB  - After the completion of a draft human genome sequence, the International Human
      Genome Sequencing Consortium has proceeded to finish and annotate each of the 24
      chromosomes comprising the human genome. Here we describe the sequencing and
      analysis of human chromosome 3, one of the largest human chromosomes. Chromosome
      3 comprises just four contigs, one of which currently represents the longest
      unbroken stretch of finished DNA sequence known so far. The chromosome is
      remarkable in having the lowest rate of segmental duplication in the genome. It
      also includes a chemokine receptor gene cluster as well as numerous loci involved
      in multiple human cancers such as the gene encoding FHIT, which contains the most
      common constitutive fragile site in the genome, FRA3B. Using genomic sequence
      from chimpanzee and rhesus macaque, we were able to characterize the breakpoints
      defining a large pericentric inversion that occurred some time after the split of
      Homininae from Ponginae, and propose an evolutionary history of the inversion.

PMID- 16641999
TI  - TMP21 is a presenilin complex component that modulates gamma-secretase but not
      epsilon-secretase activity.
AB  - The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin,
      aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass,
      membrane-bound protein complexes that are necessary for gamma-secretase and
      epsilon-secretase cleavage of selected type 1 transmembrane proteins, including
      the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can
      be generated by reconstituting these four proteins in yeast and Spodoptera
      frugiperda (sf9) cells. However, a critical but unanswered question about the
      biology of the presenilin complexes is how their activity is modulated in terms
      of substrate specificity and/or relative activities at the gamma and epsilon
      sites. A corollary to this question is whether additional proteins in the
      presenilin complexes might subsume these putative regulatory functions. The
      hypothesis that additional proteins might exist in the presenilin complexes is
      supported by the fact that enzymatically active complexes have a mass that is
      much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650
      kDa observed, compared with about 220 kDa predicted). To address these questions
      we undertook a search for presenilin-interacting proteins that differentially
      affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a
      member of the p24 cargo protein family, is a component of presenilin complexes
      and differentially regulates gamma-secretase cleavage without affecting epsilon
      secretase activity.

PMID- 16642000
TI  - Targeting C-reactive protein for the treatment of cardiovascular disease.
AB  - Complement-mediated inflammation exacerbates the tissue injury of ischaemic
      necrosis in heart attacks and strokes, the most common causes of death in
      developed countries. Large infarct size increases immediate morbidity and
      mortality and, in survivors of the acute event, larger non-functional scars
      adversely affect long-term prognosis. There is thus an important unmet medical
      need for new cardioprotective and neuroprotective treatments. We have previously
      shown that human C-reactive protein (CRP), the classical acute-phase protein that
      binds to ligands exposed in damaged tissue and then activates complement,
      increases myocardial and cerebral infarct size in rats subjected to coronary or
      cerebral artery ligation, respectively. Rat CRP does not activate rat complement,
      whereas human CRP activates both rat and human complement. Administration of
      human CRP to rats is thus an excellent model for the actions of endogenous human
      CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)
      hexane as a specific small-molecule inhibitor of CRP. Five molecules of this
      palindromic compound are bound by two pentameric CRP molecules, crosslinking and
      occluding the ligand-binding B-face of CRP and blocking its functions.
      Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute
      myocardial infarction abrogated the increase in infarct size and cardiac
      dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is
      thus a promising new approach to cardioprotection in acute myocardial infarction,
      and may also provide neuroprotection in stroke. Potential wider applications
      include other inflammatory, infective and tissue-damaging conditions
      characterized by increased CRP production, in which binding of CRP to exposed
      ligands in damaged cells may lead to complement-mediated exacerbation of tissue
      injury.

PMID- 16642001
TI  - Lysyl oxidase is essential for hypoxia-induced metastasis.
AB  - Metastasis is a multistep process responsible for most cancer deaths, and it can
      be influenced by both the immediate microenvironment (cell-cell or cell-matrix
      interactions) and the extended tumour microenvironment (for example
      vascularization). Hypoxia (low oxygen) is clinically associated with metastasis
      and poor patient outcome, although the underlying processes remain unclear.
      Microarray studies have shown the expression of lysyl oxidase (LOX) to be
      elevated in hypoxic human tumour cells. Paradoxically, LOX expression is
      associated with both tumour suppression and tumour progression, and its role in
      tumorigenesis seems dependent on cellular location, cell type and transformation
      status. Here we show that LOX expression is regulated by hypoxia-inducible factor
      (HIF) and is associated with hypoxia in human breast and head and neck tumours.
      Patients with high LOX-expressing tumours have poor distant metastasis-free and
      overall survivals. Inhibition of LOX eliminates metastasis in mice with
      orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is
      responsible for the invasive properties of hypoxic human cancer cells through
      focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may
      be required to create a niche permissive for metastatic growth. Our findings
      indicate that LOX is essential for hypoxia-induced metastasis and is a good
      therapeutic target for preventing and treating metastases.

PMID- 16642002
TI  - Detecting transient intermediates in macromolecular binding by paramagnetic NMR.
AB  - Macromolecular complex formation is governed by two opposing constraints of
      specificity and speed. Kinetic and theoretical considerations suggest that
      significant rate enhancement can be achieved either by reducing the
      dimensionality of the search process or by the creation of a short-range
      attractive potential around the target site. This implies the existence of
      transient intermediates involving non-specific binding modes. Here we show that
      intermolecular paramagnetic relaxation enhancement (PRE) provides a means of
      directly detecting the presence of, and investigating the nature of, low
      population transient intermediates under equilibrium conditions. Applying this
      approach, we characterize the search process whereby a sequence-specific
      transcription factor (the homeodomain of HOXD9) binds to non-cognate DNA sites as
      a means of enhancing the rate of specific association. The PRE data in the fast
      exchange regime reveal the presence of transient intermediates formed in a
      stochastic manner at non-cognate sites whose structure is similar to that of the
      specific complex. Two distinct search processes involving intra- as well as
      intermolecular translocations can be delineated. The intermolecular PRE method is
      general and can be readily applied to investigations of transient intermediates
      in many other macromolecular binding processes.

PMID- 16642003
TI  - Gene expression: an expression of interest.

PMID- 16642006
TI  - Strategies for mitigating an influenza pandemic.
AB  - Development of strategies for mitigating the severity of a new influenza pandemic
      is now a top global public health priority. Influenza prevention and containment
      strategies can be considered under the broad categories of antiviral, vaccine and
      non-pharmaceutical (case isolation, household quarantine, school or workplace
      closure, restrictions on travel) measures. Mathematical models are powerful tools
      for exploring this complex landscape of intervention strategies and quantifying
      the potential costs and benefits of different options. Here we use a large-scale
      epidemic simulation to examine intervention options should initial containment of
      a novel influenza outbreak fail, using Great Britain and the United States as
      examples. We find that border restrictions and/or internal travel restrictions
      are unlikely to delay spread by more than 2-3 weeks unless more than 99%
      effective. School closure during the peak of a pandemic can reduce peak attack
      rates by up to 40%, but has little impact on overall attack rates, whereas case
      isolation or household quarantine could have a significant impact, if feasible.
      Treatment of clinical cases can reduce transmission, but only if antivirals are
      given within a day of symptoms starting. Given enough drugs for 50% of the
      population, household-based prophylaxis coupled with reactive school closure
      could reduce clinical attack rates by 40-50%. More widespread prophylaxis would
      be even more logistically challenging but might reduce attack rates by over 75%.
      Vaccine stockpiled in advance of a pandemic could significantly reduce attack
      rates even if of low efficacy. Estimates of policy effectiveness will change if
      the characteristics of a future pandemic strain differ substantially from those
      seen in past pandemics.

PMID- 16642007
TI  - Animal research and the search for understanding.

PMID- 16642008
TI  - PTPN22 and invasive bacterial disease.

PMID- 16642009
TI  - GenePattern 2.0.

PMID- 16642010
TI  - Iron metabolism meets signal transduction.

PMID- 16642011
TI  - A broad band of silence.

PMID- 16642012
TI  - An adaptive path through jungle DNA.

PMID- 16642013
TI  - mtDNA clock runs out for dopaminergic neurons.

PMID- 16642016
TI  - Integrating genomics against infectious disease.
AB  - The most recent National Academies Keck Futures Initiative Conference, entitled
      'The Genomics Revolution: Implications for Treatment and Control of Infectious
      Disease', was held at the Arnold and Mabel Beckman Center in Irvine, California.
      It provided strategies and opportunities for interdisciplinary collaboration and
      incentives to innovate.

PMID- 16642017
TI  - A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and
      sporadic fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder
      of skeletal malformations and progressive extraskeletal ossification. We mapped
      FOP to chromosome 2q23-24 by linkage analysis and identified an identical
      heterozygous mutation (617G --> A; R206H) in the glycine-serine (GS) activation
      domain of ACVR1, a BMP type I receptor, in all affected individuals examined.
      Protein modeling predicts destabilization of the GS domain, consistent with
      constitutive activation of ACVR1 as the underlying cause of the ectopic
      chondrogenesis, osteogenesis and joint fusions seen in FOP.

PMID- 16642018
TI  - Epigenetic remodeling in colorectal cancer results in coordinate gene suppression
      across an entire chromosome band.
AB  - We report a new mechanism in carcinogenesis involving coordinate long-range
      epigenetic gene silencing. Epigenetic silencing in cancer has always been
      envisaged as a local event silencing discrete genes. However, in this study of
      silencing in colorectal cancer, we found common repression of the entire 4-Mb
      band of chromosome 2q.14.2, associated with global methylation of histone H3
      Lys9. DNA hypermethylation within the repressed genomic neighborhood was
      localized to three separate enriched CpG island 'suburbs', with the largest
      hypermethylated suburb spanning 1 Mb. These data change our understanding of
      epigenetic gene silencing in cancer cells: namely, epigenetic silencing can span
      large regions of the chromosome, and both DNA-methylated and neighboring
      unmethylated genes can be coordinately suppressed by global changes in histone
      modification. We propose that loss of gene expression can occur through long
      range epigenetic silencing, with similar implications as loss of heterozygosity
      in cancer.

PMID- 16642019
TI  - A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing
      and expression and is associated with increased risk of systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized
      by activation of the type I interferon (IFN) pathway. Here we convincingly
      replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele
      with SLE in four independent case-control cohorts (P = 4.4 x 10(-16)) and by
      family-based transmission disequilibrium test analysis (P = 0.0006). The
      rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5,
      allowing expression of several unique IRF5 isoforms. We also identify an
      independent cis-acting variant associated with elevated expression of IRF5 and
      linked to the exon 1B splice site. Haplotypes carrying the variant associated
      with elevated expression and lacking the exon 1B donor site do not confer risk of
      SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique
      isoforms of IRF5 is an important genetic risk factor for SLE, establishing a
      causal role for type I IFN pathway genes in human autoimmunity.

PMID- 16642020
TI  - Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome
      and Sheldon-Hall syndrome.
AB  - The genetic basis of most conditions characterized by congenital contractures is
      largely unknown. Here we show that mutations in the embryonic myosin heavy chain
      (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple
      congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third
      of all cases of Sheldon-Hall syndrome (SHS), the most common distal
      arthrogryposis. FSS and SHS mutations affect different myosin residues,
      demonstrating that MYH3 genotype is predictive of phenotype. A structure-function
      analysis shows that nearly all of the MYH3 mutations are predicted to interfere
      with myosin's catalytic activity. These results add to the growing body of
      evidence showing that congenital contractures are a shared outcome of prenatal
      defects in myofiber force production. Elucidation of the genetic basis of these
      syndromes redefines congenital contractures as unique defects of the sarcomere
      and provides insights about what has heretofore been a poorly understood group of
      disorders.

PMID- 16642021
TI  - A truncating mutation of HDAC2 in human cancers confers resistance to histone
      deacetylase inhibition.
AB  - Disruption of histone acetylation patterns is a common feature of cancer cells,
      but very little is known about its genetic basis. We have identified truncating
      mutations in one of the primary human histone deacetylases, HDAC2, in sporadic
      carcinomas with microsatellite instability and in tumors arising in individuals
      with hereditary nonpolyposis colorectal cancer syndrome. The presence of the
      HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic
      activity and renders these cells more resistant to the usual antiproliferative
      and proapoptotic effects of histone deacetylase inhibitors. As such drugs may
      serve as therapeutic agents for cancer, our findings support the use of HDAC2
      mutational status in future pharmacogenetic treatment of these individuals.

PMID- 16642022
TI  - Total insulin and IGF-I resistance in pancreatic beta cells causes overt
      diabetes.
AB  - An appropriate beta cell mass is pivotal for the maintenance of glucose
      homeostasis. Both insulin and IGF-1 are important in regulation of beta cell
      growth and function (reviewed in ref. 2). To define the roles of these hormones
      directly, we created a mouse model lacking functional receptors for both insulin
      and IGF-1 only in beta cells (betaDKO), as the hormones have overlapping
      mechanisms of action and activate common downstream proteins. Notably, betaDKO
      mice were born with a normal complement of islet cells, but 3 weeks after birth,
      they developed diabetes, in contrast to mild phenotypes observed in single
      mutants. Normoglycemic 2-week-old betaDKO mice manifest reduced beta cell mass,
      reduced expression of phosphorylated Akt and the transcription factor MafA,
      increased apoptosis in islets and severely compromised beta cell function.
      Analyses of compound knockouts showed a dominant role for insulin signaling in
      regulating beta cell mass. Together, these data provide compelling genetic
      evidence that insulin and IGF-I-dependent pathways are not critical for
      development of beta cells but that a loss of action of these hormones in beta
      cells leads to diabetes. We propose that therapeutic improvement of insulin and
      IGF-I signaling in beta cells might protect against type 2 diabetes.

PMID- 16642023
TI  - Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of
      beta cell mass.
AB  - The total mass of islets of Langerhans is reduced in individuals with type 2
      diabetes, possibly contributing to the pathogenesis of this condition. Although
      the regulation of islet mass is complex, recent studies have suggested the
      importance of a signaling pathway that includes the insulin or insulin-like
      growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol
      (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine
      threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show
      that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice)
      develop progressive hyperglycemia as a result of a loss of islet mass. The mice
      show reductions in islet density as well as in the number and size of cells.
      Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a
      marked increase in the number, but not the size, of cells and resulted in the
      restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest
      that PDK1 is important in maintenance of pancreatic cell mass and glucose
      homeostasis.

PMID- 16642024
TI  - A distant upstream enhancer at the maize domestication gene tb1 has pleiotropic
      effects on plant and inflorescent architecture.
AB  - Although quantitative trait locus (QTL) mapping has been successful in describing
      the genetic architecture of complex traits, the molecular basis of quantitative
      variation is less well understood, especially in plants such as maize that have
      large genome sizes. Regulatory changes at the teosinte branched1 (tb1) gene have
      been proposed to underlie QTLs of large effect for morphological differences that
      distinguish maize (Zea mays ssp. mays) from its wild ancestors, the teosintes (Z.
      mays ssp. parviglumis and mexicana). We used a fine mapping approach to show that
      intergenic sequences approximately 58-69 kb 5' to the tb1 cDNA confer pleiotropic
      effects on Z. mays morphology. Moreover, using an allele-specific expression
      assay, we found that sequences >41 kb upstream of tb1 act in cis to alter tb1
      transcription. Our findings show that the large stretches of noncoding DNA that
      comprise the majority of many plant genomes can be a source of variation
      affecting gene expression and quantitative phenotypes.

PMID- 16642026
TI  - Role of patient education level in predicting macrosomia among women with
      gestational diabetes mellitus.
AB  - OBJECTIVE: To evaluate the role of education level in predicting the risk of
      macrosomia among women with gestational diabetes mellitus. STUDY DESIGN: Women
      with gestational diabetes, who were referred to the California Diabetes and
      Pregnancy Sweet Success Program between June 2001 and December 2002, were
      included in the study. Multiple logistic regression was used estimate the risk of
      macrosomia, defined as a birth weight >4000 g. RESULTS: Compared to college
      educated women, high school- and middle school-educated women were 21% (relative
      risk (RR), 1.21; 95% confidence intervals (CI), 1.01-1.44) and 35% (RR, 1.35; 95%
      CI, 1.09-1.70) more likely to deliver a macrosomic infant, respectively.
      CONCLUSION: Gestational diabetics with a lower level of educational attainment
      appear to have an increased risk of macrosomia. Future studies are necessary to
      determine whether this finding reflects a variation in adherence to recommended
      treatments by education/literacy level, or if it is a surrogate marker for
      intrinsic, biological differences or differences in lifestyle.

PMID- 16642027
TI  - Thrombocytopenia among extremely low birth weight neonates: data from a
      multihospital healthcare system.
AB  - OBJECTIVES: Thrombocytopenia is common in neonatal intensive care units (NICU),
      with 18 to 35% of patients developing this problem before hospital discharge. It
      might be even more common among extremely low birth weight neonates (ELBW, < or =
      1000 g birth weight). However, little is known about thrombocytopenia in the ELBW
      population. We sought to determine the incidence, timing, causes, platelet
      transfusions given, and outcomes of thrombocytopenia among ELBW neonates. STUDY
      DESIGN: We performed a cohort analysis of all 284 ELBW neonates born during 2003
      and 2004 cared for in any of the Intermountain Healthcare level III NICUs.
      RESULTS: Multiple platelet counts were obtained in all 284 (range, 4 to 441
      platelet counts/patient). Of the 284, 208 (73%) had one or more platelet counts <
      or =150 000/microl. Most were detected during the first days of life; 80% were
      detected during the first week and only 20% were detected thereafter.
      Thrombcytopenia was more common among the smallest patients; 85% incidence among
      those < or =800 g, 60% among those 801 to 900 g, and 53% among those 901 to 1000
      g. Platelet transfusions were given to 129 of the 208 thrombocytopenic neonates.
      More than 90% were given prophylactically (the patient was not bleeding). The
      mortality rate among those that received platelet transfusions was twice that of
      those that received no platelet transfusions (P < 0.01). In 48% of cases, the
      cause of the thrombocytopenia went undiagnosed. The most common explanations were
      being small for gestational age or delivered to a hypertensive mother, DIC,
      bacterial infection, fungal infection, and necrotizing enterocolitis,
      respectively. CONCLUSIONS: We observed thrombocytopenia among ELBW neonates at a
      rate more than twice that reported among the general NICU population. Much
      remains to be discovered about the etiology and best treatments of
      thrombocytopenia among ELBW neonates.

PMID- 16642028
TI  - Accuracy of the 7-8-9 Rule for endotracheal tube placement in the neonate.
AB  - OBJECTIVE: To determine accuracy of the 7-8-9 Rule in a cohort of neonates. STUDY
      DESIGN: This study was cross-sectional in design. Seventy-five consecutive
      neonates who required oral intubation from June 2004 to November 2004 for
      cardiopulmonary failure, respiratory distress, or surfactant administration were
      the subjects of this study. The initial endotracheal tube (ETT) depth of
      insertion was determined using either an estimated birth weight or actual weight
      in the 7-8-9 Rule calculation followed by auscultation and subsequent adjustment
      if necessary. Midtracheal position was identified as the point halfway between
      the inferior clavicle and carina on a chest radiograph. The initial depth was
      compared to the midtracheal depth to determine clinical accuracy of the 7-8-9
      Rule. The depth predicted by the 7-8-9 Rule was also calculated using only actual
      weights. This predicted depth was compared to the midtracheal depth to determine
      true accuracy of the 7-8-9 Rule. Accuracy was determined using mean paired
      differences with 95% confidence intervals (CI) between initial or predicted depth
      and ideal, midtracheal ETT depth. Linear regression was used to adjust for
      confounding variables. RESULTS: Mean (range) gestational age was 32 weeks (23 to
      44 weeks) and weight was 2001 g (490 to 4400 g). Eighteen (24%) infants weighed
      1000 g or less, 20 (27%) weighed between 1001 and 2000 g, 21 (28%) weighed
      between 2001 and 3000 g, 15 (20%) weighed between 3001 and 4000 g, and one (1%)
      weighed more than 4000 g. Thirteen of the 18 extremely low birth weight infants
      weighed <750 g. The initial depth of insertion was 0.004 cm above midtracheal
      position (95% CI -0.13 to 0.14, P = 0.96). After controlling for head position,
      the initial depth did not significantly differ from the midtracheal position
      among weight groups. Predicted depth using the 7-8-9 Rule placed the ETT 0.12 cm
      above midtracheal position (95% CI -0.30 to 0.06, P = 0.20). However, after
      controlling for head position, the 7-8-9 Rule positioned the ETT significantly
      below midtracheal position in infants weighing <750 g (mean 0.62 cm; 95% CI 0.30
      to 0.93, P=0.002). CONCLUSIONS: The 7-8-9 Rule appears to be an accurate clinical
      method for endotracheal tube placement in neonates weighing more than 750 g. When
      the 7-8-9 Rule is applied to infants weighing <750 g, caution is warranted. The
      current rule may lead to an overestimated depth of insertion and potentially
      result in clinically significant consequences.

PMID- 16642029
TI  - Effect of BMP-2 gene transfer on bone healing in sheep.
AB  - Critical size defects of bone and delayed fracture healing due to metabolic
      disorders are still problems in orthopaedic surgery. Adenoviral vectors encoding
      bone morphogenetic protein-2 (Ad.BMP-2) have been used to stimulate bone
      formation in small animals. The present study evaluated the use of direct
      adenoviral gene transfer for inducing bone formation in a large animal.
      Standardized iliac crest defects were created surgically on both sides of the
      pelvic bone of white mountain sheep. The efficiency of gene transfer was
      evaluated using recombinant adenoviruses carrying the cDNA for luciferase. High
      levels of transgene expression, restricted to the site of injection, were found
      for the 1st week. Transgene expression then fell considerably, but could still be
      detected for up to 5 weeks. To investigate the effect on bone healing, Ad.BMP-2
      (10(11) particles in 200 mul saline) was unilaterally injected into iliac crest
      defects and into tibial osteotomies. The contralateral defects remained untreated
      to evaluate possible systemic effects. The controls were treated with saline
      solution. Bone formation within the defect, assessed by micro-computed tomography
      (CT) measurement at 8 weeks, and callus formation after osteotomy were
      significantly reduced following direct application of Ad.BMP-2. The retardation
      compared to untreated control animals was additionally found at the contralateral
      iliac crest indicating a systemic inhibitory effect. Histological analysis
      confirmed the CT measurement and showed an increased number of inflammatory cells
      within both defects. Antibodies against the adenovirus and the transgene product
      were detected in all treated animals. These data show a systemic retardation of
      bone formation following a single local injection of Ad.BMP-2 in sheep. This
      finding stands in contrast to the data obtained from small animal models. Further
      studies are needed to determine the contribution of the immune response to these
      results, and whether a lower dose of Ad.BMP-2 would be advantageous.

PMID- 16642030
TI  - Effective treatment of vascular endothelial growth factor refractory hindlimb
      ischemia by a mutant endothelial nitric oxide synthase gene.
AB  - Gene delivery of angiogenic growth factors is a promising approach for the
      treatment of ischemic cardiovascular diseases. However, success of this new
      therapeutic principle is hindered by the lack of critical understanding as to how
      disease pathology affects the efficiency of gene delivery and/or the downstream
      signaling pathways of angiogenesis. Critical limb ischemia occurs in patients
      with advanced atherosclerosis often exhibiting deficiency in endothelial nitric
      oxide production. Similar to these patients, segmental femoral artery resection
      progresses into severe ischemic necrosis in mice deficient in endothelial nitric
      oxide synthase (ecNOS-KO) as well as in balb/c mice. We used these models to
      evaluate the influence of severe ischemia on transfection efficiency and duration
      of transgene expression in the skeletal muscle following plasmid injection in
      combination with electroporation. Subsequently, we also explored the potential
      therapeutic effect of the phosphomimetic mutant of ecNOS gene (NOS1177D) using
      optimized delivery parameters, and found significant benefit both in ecNOS-KO and
      balb/c mice. Our results indicate that NOS1177D gene delivery to the ischemic
      skeletal muscle can be efficient to reverse critical limb ischemia in
      pathological settings, which are refractory to treatments with a single growth
      factor, such as vascular endothelial growth factor.

PMID- 16642031
TI  - The role of inflammatory bowel disease susceptibility loci in multiple sclerosis
      and systemic lupus erythematosus.
AB  - To date, three loci have been validated to confer susceptibility to inflammatory
      bowel disease (IBD): the CARD15/NOD2 gene, the discs large homolog 5 gene (DLG5),
      and the IBD5 locus on 5q31 (IBD5). We have explored the possibility that these
      loci may also be associated with susceptibility to two other chronic inflammatory
      diseases, multiple sclerosis (MS) and systemic lupus erythematosus (SLE). As the
      CARD15 risk alleles had previously been assessed in our collection of 496 MS
      trios, we focused our efforts on the DLG5 risk allele and the IBD5(risk)
      haplotype (IBD5(risk)) for MS. While there is no evidence of association within
      our MS sample with either of these polymorphisms, screening of 1027 subjects with
      SLE suggests that IBD5(risk) may have a modest contribution to disease risk in
      the subset of SLE subjects without lupus nephritis. In addition, a pooled
      analysis of existing published and unpublished data in 1305 cases of SLE
      genotyped for the CARD15 risk alleles suggests that only the CARD15(908R) IBD
      risk allele may have a strong effect on risk of SLE. Our data, therefore, suggest
      that both the CARD15 gene and the IBD5 locus may have a role as general
      susceptibility loci for certain common, genetically complex inflammatory
      diseases.

PMID- 16642032
TI  - Cytokine gene polymorphism in human disease: on-line databases, Supplement 3.
AB  - Within the past few years, the focus on cytokine single nucleotide polymorphism
      (SNP) function and association with human diseases has increased considerably.
      This third supplement to the Cytokine Gene Polymorphism in Human Disease: On-line
      database describes the positive associations of cytokine SNPs in human diseases
      described in articles published from 2002 up to 2005. A file containing a list of
      all SNPs investigated in this period of time and their association with human
      disease or expression pattern can be downloaded from the internet address
      http://www.nanea.dk/cytokinesnps/. The web pages also contain other features and
      downloads that could be useful when planning cytokine SNP association studies.

PMID- 16642033
TI  - Bcl-2 changes conformation to inhibit Bax oligomerization.
AB  - Bcl-2 inhibits apoptosis by regulating the release of cytochrome c and other
      proteins from mitochondria. Oligomerization of Bax promotes cell death by
      permeabilizing the outer mitochondrial membrane. In transfected cells and
      isolated mitochondria, Bcl-2, but not the inactive point mutants Bcl-2-G145A and
      Bcl-2-V159D, undergoes a conformation change in the mitochondrial membrane in
      response to apoptotic agonists such as tBid and Bax. A mutant Bcl-2 with two
      cysteines introduced at positions predicted to result in a disulfide bond that
      would inhibit the mobility of alpha5-alpha6 helices (Bcl-2-S105C/E152C) was only
      active in a reducing environment. Thus, Bcl-2 must change the conformation to
      inhibit tBid-induced oligomerization of integral membrane Bax monomers and small
      oligomers. The conformationally changed Bcl-2 sequesters the integral membrane
      form of Bax. If Bax is in excess, apoptosis resumes as Bcl-2 is consumed by the
      conformational change and in complexes with Bax. Thus, Bcl-2 functions as an
      inhibitor of mitochondrial permeabilization by changing conformation in the
      mitochondrial membrane to bind membrane-inserted Bax monomers and prevent
      productive oligomerization of Bax.

PMID- 16642034
TI  - A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic
      toxicity of PABPN1.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome
      characterized by progressive degeneration of particular muscles. OPMD is caused
      by short GCG repeat expansions within the gene encoding the nuclear poly(A)
      binding protein 1 (PABPN1) that extend an N-terminal polyalanine tract in the
      protein. Mutant PABPN1 aggregates as nuclear inclusions in OMPD patient muscles.
      We have created a Drosophila model of OPMD that recapitulates the features of the
      human disorder: progressive muscle degeneration, with muscle defects proportional
      to the number of alanines in the tract, and formation of PABPN1 nuclear
      inclusions. Strikingly, the polyalanine tract is not absolutely required for
      muscle degeneration, whereas another domain of PABPN1, the RNA-binding domain and
      its function in RNA binding are required. This demonstrates that OPMD does not
      result from polyalanine toxicity, but from an intrinsic property of PABPN1. We
      also identify several suppressors of the OPMD phenotype. This establishes our
      OPMD Drosophila model as a powerful in vivo test to understand the disease
      process and develop novel therapeutic strategies.

PMID- 16642035
TI  - An anchored PKA and PDE4 complex regulates subplasmalemmal cAMP dynamics.
AB  - The spatiotemporal regulation of cAMP can generate microdomains just beneath the
      plasma membrane where cAMP increases are larger and more dynamic than those seen
      globally. Real-time measurements of cAMP using mutant cyclic nucleotide-gated ion
      channel biosensors, pharmacological tools and RNA interference (RNAi) were
      employed to demonstrate a subplasmalemmal cAMP signaling module in living cells.
      Transient cAMP increases were observed upon stimulation of HEK293 cells with
      prostaglandin E1. However, pretreatment with selective inhibitors of type 4
      phosphodiesterases (PDE4), protein kinase A (PKA) or PKA/A-kinase anchoring
      protein (AKAP) interaction blocked an immediate return of subplasmalemmal cAMP to
      basal levels. Knockdown of specific membrane-associated AKAPs using RNAi
      identified gravin (AKAP250) as the central organizer of the PDE4 complex. Co
      immunoprecipitation confirmed that gravin maintains a signaling complex that
      includes PKA and PDE4D. We propose that gravin-associated PDE4D isoforms provide
      a means to rapidly terminate subplasmalemmal cAMP signals with concomitant
      effects on localized ion channels or enzyme activities.

PMID- 16642036
TI  - Primer initiation and extension by T7 DNA primase.
AB  - T7 DNA primase is composed of a catalytic RNA polymerase domain (RPD) and a zinc
      binding domain (ZBD) connected by an unstructured linker. The two domains are
      required to initiate the synthesis of the diribonucleotide pppAC and its
      extension into a functional primer pppACCC (de novo synthesis), as well as for
      the extension of exogenous AC diribonucleotides into an ACCC primer (extension
      synthesis). To explore the mechanism underlying the RPD and ZBD interactions, we
      have changed the length of the linker between them. Wild-type T7 DNA primase is
      10-fold superior in de novo synthesis compared to T7 DNA primase having a shorter
      linker. However, the primase having the shorter linker exhibits a two-fold
      enhancement in its extension synthesis. T7 DNA primase does not catalyze
      extension synthesis by a ZBD of one subunit acting on a RPD of an adjacent
      subunit (trans mode), whereas de novo synthesis is feasible in this mode. We
      propose a mechanism for primer initiation and extension based on these findings.

PMID- 16642037
TI  - Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation
      by inhibition of caspase-activated DNase.
AB  - Akt promotes cell survival through phosphorylation. The physiological functions
      of cytoplasmic Akt have been well defined, but little is known about the nuclear
      counterpart. Employing a cell-free apoptotic assay and NGF-treated PC12 nuclear
      extracts, we purified Ebp1 as a factor, which contributes to inhibition of DNA
      fragmentation by CAD. Depletion of Ebp1 from nuclear extracts or knockdown of
      Ebp1 in PC12 cells abolishes the protective effects of nerve growth factor,
      whereas overexpression of Ebp1 prevents apoptosis. Ebp1 (S360A), which cannot be
      phosphorylated by PKC, barely binds Akt or inhibits DNA fragmentation, whereas
      Ebp1 S360D, which mimics phosphorylation, strongly binds Akt and suppresses
      apoptosis. Further, phosphorylated nuclear but not cytoplasmic Akt interacts with
      Ebp1 and enhances its antiapoptotic action independent of Akt kinase activity.
      Moreover, knocking down of Akt diminishes the antiapoptotic effect of Ebp1 in the
      nucleus. Thus, nuclear Akt might contribute to suppressing apoptosis through
      interaction with Ebp1.

PMID- 16642038
TI  - Repair deficient mice reveal mABH2 as the primary oxidative demethylase for
      repairing 1meA and 3meC lesions in DNA.
AB  - Two human homologs of the Escherichia coli AlkB protein, denoted hABH2 and hABH3,
      were recently shown to directly reverse 1-methyladenine (1meA) and 3
      methylcytosine (3meC) damages in DNA. We demonstrate that mice lacking functional
      mABH2 or mABH3 genes, or both, are viable and without overt phenotypes. Neither
      were histopathological changes observed in the gene-targeted mice. However, in
      the absence of any exogenous exposure to methylating agents, mice lacking mABH2,
      but not mABH3 defective mice, accumulate significant levels of 1meA in the
      genome, suggesting the presence of a biologically relevant endogenous source of
      methylating agent. Furthermore, embryonal fibroblasts from mABH2-deficient mice
      are unable to remove methyl methane sulfate (MMS)-induced 1meA from genomic DNA
      and display increased cytotoxicity after MMS exposure. In agreement with these
      results, we found that in vitro repair of 1meA and 3meC in double-stranded DNA by
      nuclear extracts depended primarily, if not solely, on mABH2. Our data suggest
      that mABH2 and mABH3 have different roles in the defense against alkylating
      agents.

PMID- 16642039
TI  - A structural model for monastrol inhibition of dimeric kinesin Eg5.
AB  - Eg5 or KSP is a homotetrameric Kinesin-5 involved in centrosome separation and
      assembly of the bipolar mitotic spindle. Analytical gel filtration of purified
      protein and cryo-electron microscopy (cryo-EM) of unidirectional shadowed
      microtubule-Eg5 complexes have been used to identify the stable dimer Eg5-513.
      The motility assays show that Eg5-513 promotes robust plus-end-directed
      microtubule gliding at a rate similar to that of homotetrameric Eg5 in vitro. Eg5
      513 exhibits slow ATP turnover, high affinity for ATP, and a weakened affinity
      for microtubules when compared to monomeric Eg5. We show here that the Eg5-513
      dimer binds microtubules with both heads to two adjacent tubulin heterodimers
      along the same microtubule protofilament. Under all nucleotide conditions tested,
      there were no visible structural changes in the monomeric Eg5-microtubule
      complexes with monastrol treatment. In contrast, there was a substantial
      monastrol effect on dimeric Eg5-513, which reduced microtubule lattice
      decoration. Comparisons between the X-ray structures of Eg5-ADP and Eg5-ADP
      monastrol with rat kinesin-ADP after docking them into cryo-EM 3-D scaffolds
      revealed structural evidence for the weaker microtubule-Eg5 interaction in the
      presence of monastrol.

PMID- 16642040
TI  - Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic
      phenylalanine tRNA.
AB  - Wybutosine (yW) is a tricyclic nucleoside with a large side chain found at the 3'
      position adjacent to the anticodon of eukaryotic phenylalanine tRNA. yW supports
      codon recognition by stabilizing codon-anticodon interactions during decoding on
      the ribosome. To identify genes responsible for yW synthesis from uncharacterized
      genes of Saccharomyces cerevisiae, we employed a systematic reverse genetic
      approach combined with mass spectrometry ('ribonucleome analysis'). Four genes
      YPL207w, YML005w, YGL050w and YOL141w (named TYW1, TYW2, TYW3 and TYW4,
      respectively) were essential for yW synthesis. Mass spectrometric analysis of
      each modification intermediate of yW revealed its sequential biosynthetic
      pathway. TYW1 is an iron-sulfur (Fe-S) cluster protein responsible for the
      tricyclic formation. Multistep enzymatic formation of yW from yW-187 could be
      reconstituted in vitro using recombinant TYW2, TYW3 and TYW4 with S
      adenosylmethionine, suggesting that yW synthesis might proceed through sequential
      reactions in a complex formed by multiple components assembled with the precursor
      tRNA. This hypothesis is also supported by the fact that plant ortholog is a
      large fusion protein consisting of TYW2 and TYW3 with the C-terminal domain of
      TYW4.

PMID- 16642041
TI  - When a helicase is not a helicase: dsDNA tracking by the motor protein EcoR124I.
AB  - Using a combination of single molecule and bulk solution measurements, we have
      examined the DNA translocation activity of a helicase, the Type I restriction
      modification enzyme EcoR124I. We find that EcoR124I can translocate past covalent
      interstrand crosslinks, inconsistent with an obligatory unwinding mechanism.
      Instead, translocation of the intact dsDNA occurs principally via contacts to the
      sugar-phosphate backbone and bases of the 3'-5' strand; contacts to the 5'-3'
      strand are not essential for motion but do play a key role in stabilising the
      motor on the DNA. A model for dsDNA translocation is presented that could be
      applicable to a wide range of other enzyme complexes that are also labelled as
      helicases but which do not have actual unwinding activity.

PMID- 16642042
TI  - Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered
      neurotransmitter release.
AB  - Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast
      neurotransmitter release in forebrain synapses, but little is known about
      synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that
      harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin
      2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca2+
      induced but not in hypertonic sucrose-induced release, suggesting that
      synaptotagmin 2 mediates Ca2+ triggering of evoked release in brainstem synapses.
      Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a
      dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory
      and inhibitory cortical synapses also displayed a large increase in spontaneous
      release, demonstrating that this effect was shared among synaptotagmins 1 and 2.
      Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the
      Ca2+ triggering of action potential-induced release and in the restriction of
      spontaneous release, consistent with a general role of synaptotagmins in
      controlling 'release slots' for synaptic vesicles at the active zone.

PMID- 16642043
TI  - Bcl2 phosphorylation and active PKC alpha are associated with poor survival in
      AML.

PMID- 16642044
TI  - Stability and prognostic influence of FLT3 mutations in paired initial and
      relapsed AML samples.
AB  - In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine
      kinase 3 (FLT3) gene predict poor prognosis. We determined FLT3 internal tandem
      duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse
      samples from 80 pediatric and adult AML patients. One D835 point mutation was
      found in an initial pediatric AML sample. Fms-like tyrosine kinase 3/ITDs were
      present in 21 initial and 22 relapse samples (26.3 and 27.5%, respectively).
      Interestingly, FLT3/ITD positivity was related to a significantly shorter time to
      relapse, most pronounced when the ITD-positive status was found at relapse
      (P<0.001). However, FLT3/ITD status changed between diagnosis and relapse in 14
      cases. In four patients, the FLT3/ITD became undetectable at relapse in five
      patients FLT3/ITDs were only detected at relapse, and in five patients the length
      or number of FLT3/ITDs changed. Gain of FLT3/ITDs may suggest oligoclonality with
      selective outgrowth of the FLT3/ITD-positive clone, whereas losses may reflect
      ITDs in the more mature leukemic cells rather than in the leukemic stem cell, or,
      alternatively, that other genetic aberrations provided a greater selective
      advantage. Studying FLT3/ITD kinetics in minimal residual disease setting may
      provide some answers for the changes we observed. Fms-like tyrosine kinase 3/ITD
      is a relevant marker for prognosis, and remains an important target for
      therapeutic inhibition.

PMID- 16642045
TI  - Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical
      implications for human acute myeloid leukemia.
AB  - The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is crucial to many
      aspects of cell growth, survival and apoptosis, and its constitutive activation
      has been implicated in the both the pathogenesis and the progression of a wide
      variety of neoplasias. Hence, this pathway is an attractive target for the
      development of novel anticancer strategies. Recent studies showed that PI3K/Akt
      signaling is frequently activated in acute myeloid leukemia (AML) patient blasts
      and strongly contributes to proliferation, survival and drug resistance of these
      cells. Upregulation of the PI3K/Akt network in AML may be due to several reasons,
      including FLT3, Ras or c-Kit mutations. Small molecules designed to selectively
      target key components of this signal transduction cascade induce apoptosis and/or
      markedly increase conventional drug sensitivity of AML blasts in vitro. Thus,
      inhibitory molecules are currently being developed for clinical use either as
      single agents or in combination with conventional therapies. However, the
      PI3K/Akt pathway is important for many physiological cellular functions and, in
      particular, for insulin signaling, so that its blockade in vivo might cause
      severe systemic side effects. In this review, we summarize the existing knowledge
      about PI3K/Akt signaling in AML cells and we examine the rationale for targeting
      this fundamental signal transduction network by means of selective
      pharmacological inhibitors.

PMID- 16642046
TI  - Immunophenotypic identification of acute myeloid leukemia with monocytic
      differentiation.

PMID- 16642047
TI  - IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on
      B-cell prolymphocytic leukemia (B-PLL).
AB  - B-prolymphocytic leukemia (B-PLL) is a rare disease with poor prognosis. To
      further characterize the biological features of this disease, we analyzed
      immunoglobulin heavy chain (IgVH) mutations, ZAP-70 and CD38 in 19 cases with de
      novo B-PLL. Immunoglobulin heavy chain genes analysis showed an unmutated pattern
      (>98% homology to germ line) in 9/17 cases (53%), with 100% homology in eight. In
      the remaining, it ranged from 90 to 97.4%, with three cases slightly mutated (98
      95%) and five heavily mutated (<95%). All B-PLL utilized members of VH3 (11/17)
      and VH4 (6/17) families, with V3-23, V4-59 and V4-34 gene accounting for more
      than half of them, regardless of mutational status. ZAP-70, assessed by flow
      cytometry, ranged from 1 to 91% cells, being > or =20% in 57% of cases. CD38
      ranged from 1 to 99% (median 21%). There was no correlation between IgVH status
      and ZAP-70 or CD38 expression, but male gender and del(17p) were more common in
      the unmutated group. Neither IgVH mutations, CD38 expression nor del(17p)
      influenced patients' outcome. Unexpectedly, ZAP-70+ B-PLL patients survived
      longer (40 months) than ZAP-70- B-PLL (8 months). B-PLL appears biologically
      heterogeneous regarding IgVH mutations, ZAP-70 and CD38 expression, showing a
      pattern distinct from that of other lymphoproliferative disorders.

PMID- 16642048
TI  - Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic
      myelogenous leukemia patients: a retrospective analysis from the French
      intergroup of CML (Fi(phi)-LMC GROUP).
AB  - The emergence of ABL point mutations is the most frequent cause for imatinib
      resistance in chronic myelogenous leukemia (CML) patients and can occur during
      any phase of the disease; however, their clinical impact remains controversial.
      In this study, we retrospectively analyzed the predictive impact of 94 BCR-ABL
      kinase domain mutations (18 T315I, 26 P-loop, 50 in other sites) found in 89
      imatinib-resistant CML patients. At imatinib onset, 64% of patients (57/89) were
      in chronic phase (CP), 24% (21/89) in accelerated phase (AP) and 12% (11/89) in
      blastic phase (BP). T315I and P-loop mutations were preferentially discovered in
      accelerated phase of BP CML, and other types of mutations in CP (P=0.003). With a
      median follow-up of 39.2 months (6.3-67.2), since imatinib initiation, overall
      survival (OS) was significantly worse for P-loop (28.3 months) and for T315I
      (12.6 months), and not reached for other mutations (P=0.0004). For CP only,
      multivariate analysis demonstrated a worse OS for P-loop mutations (P=0.014), and
      a worse progression-free survival (PFS) for T315I mutations (P=0.014). Therefore,
      P-loop and T315I mutations selectively impair the outcome of imatinib-resistant
      CML patients, in contrast to other mutations, which may benefit from dose
      escalation of imatinib, able to improve or stabilize disease response.

PMID- 16642049
TI  - Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway
      inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells.
AB  - The Insulin-like growth factor-1 receptor (IGF-1R) is overexpressed in a variety
      of tumors including breast, prostate and myeloma. Thus, IGF-1R and its downstream
      signaling effectors are good candidates for molecular-based targeted antitumor
      therapies. Indeed, protein inhibitors of IGF-1R signaling and IGF-1R blocking
      antibodies are undergoing clinical trials. Herein, the molecular basis for
      antibody-mediated IGF-1R signal inhibition has been investigated in a
      hematopoietic cell line model, FDC-P1, that has been rendered interleukin-3
      independent in a ligand-dependent manner through retroviral-mediated expression
      of IGF-1R (FD/IGF-1R). Furthermore, the ability of an anti-IGF-1R antibody to
      synergize with signal-transduction pathway inhibitors and induce apoptosis was
      determined. The alphaIGF-1R antibody, A12, was capable of arresting IGF-1 or
      insulin-induced FD/IGF-1R cell proliferation in the G1 phase of the cell cycle
      and resulted in apoptotic induction. A12 effectiveness could be potentiated
      through combination treatment with small molecule inhibitors of the
      Ras/Raf/MEK/ERK or PI3K/Akt/mTOR pathways. These results validate the use of the
      FD/IGF-1R cells to evaluate the effectiveness and mechanisms of targeted IGF-1R
      therapeutic strategies.

PMID- 16642050
TI  - Coherence polarization filtering and relation with intrinsic degrees of
      coherence.
AB  - It is demonstrated for stationary fields that when the polarization state of the
      electric field can be modified arbitrarily the maximal value of the modulus of
      the degree of coherence proposed by Wolf [Phys. Lett. A312, 263 (2003)] is equal
      to the largest intrinsic degree of coherence. In addition, when the light is a
      mixing of a coherent light that satisfies the factorization condition in the two
      spatial variables with a statistically uncorrelated, partially coherent,
      perfectly polarized light, but with a nonparallel polarization state, we show
      that the polarization modifications that maximize the modulus of the Wolf degree
      of coherence lead to a light that also satisfies the factorization condition.

PMID- 16642051
TI  - Propagation of spatially partially coherent emission from a vertical-cavity
      surface-emitting laser.
AB  - Recently we observed a strong reduction of spatial coherence of the emission of
      large-aperture vertical-cavity surface-emitting lasers when they are driven by
      microsecond electrical pulses [Opt. Express 13, 9337 (2005)]. We study the
      influence of this partial spatial coherence on the propagation characteristics.
      The spatial decoherence manifests itself in the formation of a Gaussian far-field
      intensity distribution. We measure the transverse pulse profile from near to far
      field and see that the shape-invariant far-field regime starts after 140 microm
      in the pulsed regime as opposed to several centimeters in continuous wave
      operation. This value matches quantitatively calculations made with a novel
      partially coherent propagation model without any free fitting parameters.

PMID- 16642052
TI  - Design of near-field irregular diffractive optical elements by use of a
      multiresolution direct binary search method.
AB  - A multiresolution direct binary search iterative procedure is used to design
      small dielectric irregular diffractive optical elements that have subwavelength
      features and achieve near-field focusing below the diffraction limit. Designs
      with a single focus or with two foci, depending on wavelength or polarization,
      illustrate the possible functionalities available from the large number of
      degrees of freedom. These examples suggest that the concept of such elements may
      find applications in near-field lithography, wavelength-division multiplexing,
      spectral analysis, and polarization beam splitters.

PMID- 16642053
TI  - Band-edge-induced Bragg diffraction in two-dimensional photonic crystals.
AB  - Two-dimensional photonic crystals composed of two orthogonal volume diffraction
      gratings have been photogenerated in photopolymers. When the read beam is set at
      the Bragg angle, the diffraction efficiency of the transmission grating is
      strongly enhanced at the band edge of the reflection grating recorded in the
      material. Such a device provides Bragg operation and enhancement of the
      diffraction efficiency of the thin diffraction grating together with good
      wavelength selectivity. Such advantages could be interesting for optical signal
      processing.

PMID- 16642054
TI  - Optical labeling scheme using polarization shift keying/vestigial sideband
      carrier-suppressed return-to-zero orthogonal modulation.
AB  - We propose and experimentally demonstrate a polarization shift keying label and a
      vestigial sideband carrier-suppressed return-to-zero payload scheme for a 43
      Gbit/s all-optical label switching network. This scheme has a narrow channel
      bandwidth and a low penalty due to polarization mode dispersion impairments,
      which confirm it as a candidate technique for the next generation of optical
      networks.

PMID- 16642055
TI  - Differential toolbox to shape dispersion behavior in photonic crystal fibers.
AB  - We present an analytical procedure to compute the first derivatives of the
      propagation constants with respect to several structural parameters in photonic
      crystal fibers (PCFs). From them we can easily evaluate the same derivatives of
      other directly related magnitudes. The above derivatives provide the trend of the
      magnitude at issue, which allows us to take advantage of a gradient-based
      algorithm to shape the properties of the guiding structure. In this way we
      implement an optimization process to carry out real inverse design in PCFs. We
      focus our attention on designing PCFs with a specific chromatic dispersion
      behavior. Likewise, the same approach makes it possible to analyze their
      fabrication tolerances.

PMID- 16642056
TI  - Optic sensors of high refractive-index responsivity and low thermal cross
      sensitivity that use fiber Bragg gratings of >80 degrees tilted structures.
AB  - For the first time to the authors' knowledge, fiber Bragg gratings (FBGs) with
      >80 degrees tilted structures have been fabricated and characterized. Their
      performance in sensing temperature, strain, and the surrounding medium's
      refractive index was investigated. In comparison with normal FBGs and long-period
      gratings (LPGs), >80 degrees tilted FBGs exhibit significantly higher refractive
      index responsivity and lower thermal cross sensitivity. When the grating sensor
      was used to detect changes in refractive index, a responsivity as high as 340
      nm/refractive-index unit near an index of 1.33 was demonstrated, which is three
      times higher than that of conventional LPGs.

PMID- 16642057
TI  - Impact of interstitial air holes on a wide-bandwidth rejection filter made from a
      photonic crystal fiber.
AB  - We have investigated the spectral properties of a band rejection filter made with
      a long-period fiber grating written in photonic crystal fiber that has
      interstitial air holes. Experiments showed that only one mode was coupled
      strongly to the fundamental core mode over a 600 nm spectral range. The central
      wavelength of the filter could be tuned over that range without being appreciably
      affected by any other mode. By using the multipole method, we found that the
      interstitial air holes of the photonic crystal fiber played a critical role in
      limiting the number of modes that could strongly interact with the fundamental
      mode and in obtaining well-separated resonance peaks. Excellent agreement between
      theory and experiment was obtained.

PMID- 16642058
TI  - Phase-only sampled 45 channel fiber Bragg grating written with a diffraction
      compensated phase mask.
AB  - A novel phase-only sampled 45 channel fiber Bragg grating (channel spacing, 100
      GHz) with high interchannel and intrachannel reflection uniformity and precise
      dispersion matching capability to an 80 km SMF-28 fiber is demonstrated. This
      grating is fabricated by the side-writing technique, in which phase information
      of continuous phase-only sampling is completely incorporated into a diffraction
      compensated phase mask.

PMID- 16642059
TI  - Mode power distribution effect in white-light multimode fiber extrinsic Fabry
      Perot interferometric sensor systems.
AB  - Theoretical and experimental results have shown that mode power distribution
      (MPD) variations could significantly vary the phase of spectral fringes from
      multimode fiber extrinsic Fabry-Perot interferometric (MMF-EFPI) sensor systems,
      owing to the fact that different modes introduce different extra phase shifts
      resulting from the coupling of modes reflected at the second surface to the lead
      in fiber end. This dependence of fringe pattern on MPD could cause measurement
      errors in signal demodulation methods of white-light MMF-EFPI sensors that
      implement the phase information of the fringes.

PMID- 16642060
TI  - Bit error rate improvement by nonlinear optical decision element.
AB  - We present a novel approach to the improvement of the bit error rate (BER) in
      optical communications. We propose a design of advanced optical receiver enhanced
      by a nonlinear all-optical decision element. As a particular example, we
      demonstrate a substantial improvement in the BER over the conventional receiver
      for operation at 40 Gbits/s.

PMID- 16642061
TI  - Analysis of a collinear holographic storage system: introduction of pixel spread
      function.
AB  - Image formation in a collinear holographic storage system was analyzed. The
      wavefront from each pixel of a spatial light modulator was regarded as a plane
      wave in the recording medium, and its wave vector was determined by the position
      of the pixel. The hologram in the recording medium was treated as the summation
      of all gratings written by all combinations of two plane waves. The image of a
      data page was formed by diffraction of the reference waves by all gratings. The
      results of the simulation showed good agreement with experiment. We introduced
      the pixel spread function to describe the image formation characteristics.
      Analysis of the pixel spread function reveals that a radial-line pixel pattern
      for reference waves gave a sharper image than other reference pixel patterns. It
      is also shown that a random phase modulation applied to each reference pixel
      improved the image formation.

PMID- 16642062
TI  - Immersion digital in-line holographic microscopy.
AB  - Digital in-line holographic microscopy is a promising new tool for high
      resolution imaging. We demonstrate, by using latex beads, that a considerable
      increase in numerical aperture, and, therefore, resolution can be achieved if the
      space between a source and a CCD camera chip is filled with a high refractive
      index medium. The high refractive index medium implies a shorter effective
      wavelength so that submicrometer resolution can be obtained with laser light in
      the visible range.

PMID- 16642063
TI  - Sub-38 nm resolution tabletop microscopy with 13 nm wavelength laser light.
AB  - We have acquired images with a spatial resolution better than 38 nm by using a
      tabletop microscope that combines 13 nm wavelength light from a high-brightness
      tabletop laser and Fresnel zone plate optics. These results open a gateway to the
      development of compact and widely available extreme-ultraviolet imaging tools
      capable of inspecting samples in a variety of environments with a 15-20 nm
      spatial resolution and a picosecond time resolution.

PMID- 16642064
TI  - Fiber-optic laser Doppler turbine tip clearance probe.
AB  - A laser Doppler based method for in situ single blade tip clearance measurements
      of turbomachines with high precision is presented for what we believe is the
      first time. The sensor is based on two superposed fanlike interference fringe
      systems generated by two laser wavelengths from a fiber-coupled, passive, and
      therefore compact measurement head employing diffractive optics. Tip clearance
      measurements at a transonic centrifugal compressor performed during operation at
      50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured
      uncertainty of the tip position was less than 20 microm, a factor of 2 more
      accurate than that of capacitive probes. The sensor offers great potential for in
      situ and online high-precision tip clearance measurements of metallic and
      nonmetallic turbine blades.

PMID- 16642065
TI  - Three-dimensional particle imaging by wavefront sensing.
AB  - We present two methods for three-dimensional particle metrology from a single two
      dimensional view. The techniques are based on wavefront sensing where the three
      dimensional location of a particle is encoded into a single image plane. The
      first technique is based on multiplanar imaging, and the second produces three
      dimensional location information via anamorphic distortion of the recorded
      images. Preliminary results show that an uncertainty of 8 microm in depth can be
      obtained for low-particle density over a thin plane, and an uncertainty of 30
      microm for higher particle density over a 10 mm deep volume.

PMID- 16642066
TI  - Electric field enhancement in guided-mode resonance filters.
AB  - Electric fields inside guided-mode resonance filters (GMRFs) may be intensified
      by resonance effects. The electric field enhancement is investigated in two
      GMRFs: one is resonant at normal incidence, the other at oblique incidence. It is
      shown that the two GMRFs exhibit different behaviors in their electric
      enhancement. Differences between the electric field distributions of the two
      GMRFs arise because coupling between counterpropagating modes occurs in the first
      case. It is also shown that the order of the electric field of maximum amplitude
      can be controlled by modulation of the dielectric constant of the grating.

PMID- 16642067
TI  - Light-wave guidance through stratified photonic crystal metamaterials synthesized
      by superinductive layers of metallic nanostrips.
AB  - The electrodynamic properties of a novel class of photonic-crystal metamaterial
      platform entirely synthesized by ultralow-refractive-index suspended nanostrips
      embedded in a dielectric matrix are described and investigated. The optical
      properties of the homogeneous metamaterial platform can be understood on the
      basis of equivalent distributed circuit extraction from an electromagnetic model
      that has negatively distributed superinductive properties. Low propagation loss,
      temperature-insensitive characteristics, and ultracompact size are the main
      advantages of the proposed technology, making this new type of metamaterial an
      excellent candidate for use in compact multilayer nanophotonic integrated
      systems.

PMID- 16642068
TI  - Ultrahigh-quality photonic crystal cavity in GaAs.
AB  - Membrane-based photonic crystal GaAs cavities with a double-heterostructure
      design were investigated. They show the highest quality factors for GaAs photonic
      crystal cavities to date, exhibiting quality factors higher than 10(5). The
      resonances of these cavities were fine-tuned in steps smaller than 2 nm by
      digital etching.

PMID- 16642069
TI  - Guided-wave second-harmonic generation in a LiNbO3 nonlinear photonic crystal.
AB  - We demonstrate twin-beam second-harmonic generation from telecommunications
      wavelengths in an optimized buried reverse proton exchanged planar waveguide made
      in 2D hexagonally poled LiNbO3. Experiments carried out with a nanosecond narrow
      bandwidth, high-power fiber source thoroughly explored the response of the
      nonlinear photonic crystal device in terms of its power, wavelength, and angle
      tunability.

PMID- 16642070
TI  - Enhanced stimulated Raman scattering in slow-light photonic crystal waveguides.
AB  - We investigate for the first time, to our knowledge, the enhancement of the
      stimulated Raman scattering in slow-light silicon-on-insulator (SOI) photonic
      crystal line defect waveguides. By applying the Bloch-Floquet formalism to the
      guided modes in a planar photonic crystal, we develop a formalism that relates
      the intensity of the downshifted Stokes signal to the pump intensity and the
      modal group velocities. The formalism is then applied to two prospective schemes
      for enhanced stimulated Raman generation in slow-light photonic crystal
      waveguides. The results demonstrate a maximum factor of 104(66,000) enhancement
      with respect to SOI channel waveguides.

PMID- 16642071
TI  - Planar photonic crystals infiltrated with liquid crystals: optical
      characterization of molecule orientation.
AB  - Nematic liquid crystals are infiltrated into InP-based planar photonic crystals.
      Optical measurements as a function of temperature and polarization are used to
      study the average director field configuration in the nanometer-size holes: a
      planar equilibrium state is found.

PMID- 16642072
TI  - Ultrawide tuning of photonic microcavities via evanescent field perturbation.
AB  - Evanescent field perturbation of an integrated microring resonator is examined as
      a means of achieving high-fidelity reversible tuning of photonic microcavities
      over large wavelength ranges. A 1.7% wavelength tuning is achieved through the
      use of a novel silica fiber probe that provides access to the evanescent field of
      an air-clad high-index-contrast ring resonator. As the microring is perturbed,
      the probe-ring distance is found through simultaneous nanometric distance
      calibration and force measurements. Experimental results agree well with
      theoretical tuning. Possible microelectromechanical systems implementation of
      this effect is discussed, as well as avenues for improvement of the tuning range.

PMID- 16642073
TI  - Controlling bichromatic emission in scattering gain media.
AB  - It is experimentally shown that the competition between the two lasing modes of
      bichromatic emission in a dye solution with nanoparticle scatterers within the
      diffuse regime can be externally controlled by varying only the excitation beam
      diameter and the radiation detector position. It is established that this feature
      is a consequence of the changes in the reabsorption process strengths between
      monomer and dimer dye aggregates. The controllable switching of these lasing
      modes could open the real possibility of implementing previously suggested
      applications for this effect as optical switches.

PMID- 16642074
TI  - Coherent combination of high-power, zigzag slab lasers.
AB  - We demonstrate a scalable architecture for a high-power, high-brightness, solid
      state laser based on coherent combinations of master oscillator power amplifier
      chains. A common master oscillator injects a sequence of multikilowatt Nd:YAG
      zigzag slab amplifiers. Adaptive optics correct the wavefront of each amplified
      beamlet. The beamlets are tiled side by side and actively phase locked to form a
      single output beam. The laser produces 19 kW with beam quality <2x diffraction
      limited. To the best of our knowledge, this is the brightest cw solid-state laser
      demonstrated to date.

PMID- 16642075
TI  - Lasing modes in a spiral-shaped dielectric microcavity.
AB  - The resonance patterns and lasing modes in a spiral-shaped dielectric microcavity
      are investigated through passive and active medium calculations. We find that the
      high-Q resonance modes are whispering-gallery-like modes, and these resonance
      modes can be easily excited as lasing modes. We also find that the quasi-scarred
      resonance mode, which shows strong directional emission beams from the cavity
      boundary, can be excited with selectively applied external pumping. Through a
      spectral analysis of the time evolution of the light field, the competition
      between these lasing modes is discussed.

PMID- 16642076
TI  - Efficient, high-brightness wavelength-beam-combined commercial off-the-shelf
      diode stacks achieved by use of a wavelength-chirped volume Bragg grating.
AB  - We report a method of scaling the spatial brightness from commercial off-the
      shelf diode laser stacks through wavelength beam combining, by use of a linearly
      wavelength-chirped volume Bragg grating (VBG). Using a three-bar commercial stack
      of broad-area lasers and a VBG, we demonstrate 89.5 W cw of beam-combined output
      with a beam-combining efficiency of 75%. The output beam has a propagation factor
      M2 approximately 26 on the slow axis and M2 approximately 21 on the fast axis.
      This corresponds to a brightness of approximately 20 MW/cm2 sr. To our knowledge,
      this is the highest brightness broad-area diode laser system. We achieve 81%
      coupling efficiency into a 100 microm, 0.22 N.A. fiber.

PMID- 16642077
TI  - Bragg selectivity of space-charge gratings in multidomain lithium niobate
      crystals.
AB  - It is shown experimentally and theoretically that a partial domain reversal in
      ferroelectric lithium niobate crystals containing a previously imprinted
      photorefractive space-charge grating results in a highly unusual change of the
      angular Bragg selectivity. This carries important in situ information about
      domain structures, including the quality of periodically poled samples.

PMID- 16642078
TI  - Single-slit split-ring resonators at optical frequencies: limits of size scaling.
AB  - We present magnetic metamaterials composed of 35 nm minimum feature-size gold
      split-ring resonators with a fundamental magnetic resonance at a wavelength of
      900 nm. Corresponding calculations reveal excellent agreement with the
      experiments and show that the limits of size scaling have been reached.

PMID- 16642079
TI  - Doppler optical coherence tomography with a micro-electro-mechanical membrane
      mirror for high-speed dynamic focus tracking.
AB  - An elliptical microelectromechanical system (MEMS) membrane mirror is
      electrostatically actuated to dynamically adjust the optical beam focus and track
      the axial scanning of the coherence gate in a Doppler optical coherence
      tomography (DOCT) system at 8 kHz. The MEMS mirror is designed to maintain a
      constant numerical aperture of approximately 0.13 and a spot size of
      approximately 6.7 microm over an imaging depth of 1mm in water, which improves
      imaging performance in resolving microspheres in gel samples and Doppler shift
      estimation precision in a flow phantom. The mirror's small size (1.4 mm x 1 mm)
      will allow integration with endoscopic MEMS-DOCT for in vivo applications.

PMID- 16642080
TI  - Paired-angle-rotation scanning optical coherence tomography forward-imaging
      probe.
AB  - We report a novel forward-imaging optical coherence tomography (OCT), needle
      probe paired-angle-rotation scanning OCT (PARS-OCT) probe. The probe uses two
      rotating angled gradient-index lenses to scan the output OCT probe beam over a
      wide angular arc (approximately 19 degrees half-angle) of the region forward of
      the probe. Among other advantages, this probe design is readily amenable to
      miniaturization and is capable of a variety of scan modes, including volumetric
      scans. To demonstrate the advantages of the probe design, we have constructed a
      prototype probe with an outer diameter of 1.65 mm and employed it to acquire four
      OCT images, with a 45 degrees angle between adjacent images, of the gill
      structure of a Xenopus laevis tadpole. The system sensitivity was measured to be
      93 dB by using the prototype probe with an illumination power of 450 microW on
      the sample. Moreover, the axial and the lateral resolutions of the probe are 9.3
      and 10.3-12.5 microm, respectively.

PMID- 16642081
TI  - MEMS-based adaptive optics scanning laser ophthalmoscopy.
AB  - We have developed a compact, robust adaptive optics (AO) scanning laser
      ophthalmoscope using a microelectromechanical (MEMS) deformable mirror (DM).
      Facilitated with a Shack-Hartmann wavefront sensor, the MEMS-DM-based AO operates
      a closed-loop modal wave aberration correction for the human eye and reduces wave
      aberrations in most eyes to below 0.1 microm rms. Lateral resolution is enhanced,
      and images reveal a clear cone mosaic near the foveal center. The significant
      increase in throughput allows for a confocal pinhole whose diameter is less than
      the Airy disc of the collection lens, thereby fully exploiting the axial
      resolution capabilities of the system.

PMID- 16642082
TI  - Resolving the complex conjugate ambiguity in Fourier-domain OCT by harmonic lock
      in detection of the spectral interferogram.
AB  - A method of resolving the complex conjugate ambiguity in Fourier-domain OCT is
      described. The complex differential spectral interferogram is obtained by
      simultaneous acquisition of the first and second harmonics of the ac component of
      the phase-modulated interferogram. The harmonics represent the imaginary and real
      parts of the interferogram, respectively. The complex conjugate rejection ratio
      is found to be at least 45 dB and is limited by background noise.

PMID- 16642083
TI  - Full-field optical sectioning and three-dimensional localization of fluorescent
      particles using focal plane modulation.
AB  - We present a technique for imaging fluorescent particles based on the axial
      modulation of the objective's focal plane position. This technique provides full
      field optical sectioning and can be used to localize the fluorophores in three
      dimensions. We describe the technique and apply it to image 200 nm diameter
      fluorescent beads immobilized in a gel. We show that full-field optical
      sectioning is obtained and that the beads are localized with a precision of 10 nm
      in the transverse plane and 14 nm in the axial direction.

PMID- 16642084
TI  - Energy and average power scalable optical parametric chirped-pulse amplification
      in yttrium calcium oxyborate.
AB  - Optical parametric chirped-pulse amplification (OPCPA) in nonlinear crystals has
      the potential to produce extremes of peak and average power but is limited either
      in energy by crystal growth issues or in average power by crystal thermo-optic
      characteristics. Recently, large (7.5 cm diameter x 25 cm length) crystals of
      yttrium calcium oxyborate (YCOB) have been grown and utilized for high-average
      power second-harmonic generation. Further, YCOB has the necessary thermo-optic
      properties required for scaling OPCPA systems to high peak and average power
      operation for wavelengths near 1 microm. We report what is believed to be the
      first use of YCOB for OPCPA. Scalability to higher peak and average power is
      addressed.

PMID- 16642085
TI  - Observation of the snake instability of a spatially extended temporal bright
      soliton.
AB  - The transverse snake instability of the bright soliton solution of the (2+1)
      dimensional hyperbolic nonlinear Schrodinger equation is experimentally studied.
      We observed this instability in the spatial distribution of the temporal spectrum
      of spatially extended femtosecond pulses propagating in normally dispersive self
      defocusing planar semiconductor waveguide.

PMID- 16642086
TI  - Single-frequency quasi-continuous red radiation generated by a green-pumped
      singly resonant optical parametric oscillator.
AB  - We demonstrate the operation of a quasi-continuous-wave optical parametric
      oscillator (OPO) in the red part of the visible spectrum by direct pumping from a
      frequency-doubled quasi-continuous-wave Nd:YAG laser. The OPO is singly resonant
      and based on a MgO-doped periodically poled stoichiometric lithium tantalate
      crystal. A single-frequency 1.2 W output power is obtained when an etalon is
      inserted inside the cavity.

PMID- 16642087
TI  - Photon-pair generation by four-wave mixing in optical fibers.
AB  - We present a theory to quantify a fundamental limit on correlated photon pairs
      generated through four-wave mixing inside optical fibers in the presence of
      spontaneous Raman scattering (SpRS). Our theory is able to explain current
      experimental data. We show that if correlated photon pairs are generated with
      polarization orthogonal to the pump the effect of SpRS is significantly reduced
      over a broad spectral region extending from 5 to 15 THz.

PMID- 16642088
TI  - Sub-20 fs visible pulses with 750 nJ energy from a 100 kHz noncollinear optical
      parametric amplifier.
AB  - We demonstrate the operation of a 100 kHz noncollinear optical parametric
      amplifier that is pumped by just a few microjoules of 800 nm pulses with 50 fs
      duration. The device delivers sub-20 fs pulses tunable from 460 nm to beyond 1
      microm and pulse energies up to 750 nJ when it is pumped with 7 microJ of energy.
      The design of the single-stage amplifier has been carefully optimized, and the
      design considerations are discussed.

PMID- 16642089
TI  - Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman
      scattering microscopy.
AB  - The signal and idler beams from a picosecond, synchronously pumped optical
      parametric oscillator (OPO) provide the two colors necessary for coherent anti
      Stokes Raman scattering (CARS) microscopy. The OPO provides a continuously
      tunable frequency difference between the two beams over a broad range of Raman
      shifts (100-3700 cm(-1)) by varying the temperature of a single nonlinear
      crystal. The near-infrared output (900-1300 nm) allows for deep penetration into
      thick samples and reduced nonlinear photodamage. Applications of this light
      source to in vivo cell and ex vivo tissue imaging are demonstrated.

PMID- 16642090
TI  - Dispersion tailoring and soliton propagation in silicon waveguides.
AB  - The dispersive properties of silicon-on-insulator (SOI) waveguides are studied by
      using the effective-index method. Extensive calculations indicate that an SOI
      waveguide can be designed to have its zero-dispersion wavelength near 1.5 microm
      with reasonable device dimensions. Numerical simulations show that soliton-like
      pulse propagation is achievable in such a waveguide in the spectral region at
      approximately 1.55 microm. The concept of path-averaged solitons is used to
      minimize the impact of linear loss and two-photon absorption.

PMID- 16642091
TI  - Enhancement of harmonic generation by Fresnel-lensing effects.
AB  - We present experimental results of enhanced second- and third-harmonic generation
      efficiency from Fresnel-lensing effects. We obtained enhancement by a factor of 6
      in the third-harmonic yield by simply limiting the laser beam with an iris.
      Higher enhancement factors (up to 16) were obtained with a Fresnel zone plate.
      The experimental findings are in good agreement with the results of a simple
      theoretical analysis.

PMID- 16642092
TI  - Long-range multifilamentation of femtosecond laser pulses versus air pressure.
AB  - We examine the nonlinear dynamics of femtosecond filaments in air at different
      pressures. Emphasis is placed on the changes in multiple filamentation patterns
      produced by terawatt laser pulses. Principal modifications induced by pressure
      variations apply to the onset distance, size, and number of the filaments inside
      the laser bundle.

PMID- 16642093
TI  - White light micrograting multiplexing for high density data storage.
AB  - Recording of multiplexed microholographic gratings with improved recording volume
      for high density optical data storage is proposed and demonstrated. By using a
      hybrid diffractive-refractive objective lens with extended depth of focus, we
      have achieved a recording beam size of approximately 1 microm and a focal depth
      of 20 microm. Multiple gratings corresponding to spectral lines within the 400
      650 nm spectral band have been successfully multiplexed in a single recording
      spot or pit of size 1.25 microm on a DuPont photopolymer film using a white light
      source along with narrowband filters or dispersion elements, thus demonstrating
      the storage of multiple bits in a single pit. Simultaneous readout of multiple
      bits in a single storage pit is accomplished with a microspectrometer-type
      readout head using a white light source.

PMID- 16642094
TI  - Laser-fabricated dielectric optical components for surface plasmon polaritons.
AB  - Fabrication of dielectric optical components for surface plasmon polaritons
      (SPPs) by two-photon polymerization (2PP) is studied. This direct-write
      femtosecond laser technology provides a low-cost and flexible method for the
      fabrication and investigation of plasmonic structures and optical components.
      Using the 2PP technique, we fabricated narrow dielectric ridges with dimensions
      as small as 150 nm on metal surfaces. SPP excitation with the laser-fabricated
      structures and guiding along them are demonstrated.

PMID- 16642095
TI  - Prism-based multicolor fluorescence correlation spectrometer.
AB  - We report the design and application of a prism-based detection system for
      fluorescence (cross) correlation spectroscopy. The system utilizes a single laser
      wavelength for the simultaneous excitation of several dyes of different emission
      spectra. Fluorescence light is spectrally separated with a prismatic setup, and
      wavelengths are selected by scanning a fiber-coupled avalanche photodiode across
      the image spots. Multicolor autocorrelations are demonstrated with standard and
      tandem dyes, and fluorescence cross-correlation measurements of biotinylated
      nanocontainers and streptavidin are presented. This spectrometer offers high
      optical stability and no focal volume mismatch for the multicolor detection of
      molecular dynamics and interactions, with single-molecule sensitivity.

PMID- 16642096
TI  - Morphology-dependent photonic circuit elements.
AB  - We theoretically propose and experimentally demonstrate the design of a novel one
      dimensional ringlike macroscopic optical circuit element. The similarity between
      morphologies of an optical planar waveguide and a whispering-gallery axially
      symmetric solid-state resonator is used.

PMID- 16642097
TI  - Development of high-throughput, high-damage-threshold beam separator for 13 nm
      high-order harmonics.
AB  - We demonstrate a high-throughput, high-damage-threshold beam separator for
      wavelengths shorter than 30 nm, which uses a 10 nm thick niobium nitrogen film
      prepared on a Si substrate, set at the Brewster angle relative to the pump
      wavelength. The film was deposited by rf reactive magnetron sputtering on a Si
      substrate. The beam separator has an attenuation ratio of 0.01 and a damage
      threshold intensity of at least 0.8 TW/cm2 for a 26 fs pump pulse. The measured
      reflectivity of the beam separator exceeded 70% in a wavelength range of 13-18
      nm. This broadband beam separator may be used to eliminate energetic laser pulses
      from longitudinally pumped x ray lasers as well as from high-order harmonics.

PMID- 16642098
TI  - Liquid-core optical ring-resonator sensors.
AB  - We have demonstrated a novel sensor architecture based on a liquid-core optical
      ring-resonator (LCORR) in which a fused silica capillary is utilized to carry the
      aqueous sample and to act as the ring resonator. The wall thickness of the LCORR
      is controlled to a few micrometers to expose the whispering gallery mode to the
      aqueous core. Optical characterization with a water-ethanol mixture shows that
      the spectral sensitivity of the LCORR sensor is approximately 2.6 nm per
      refractive index unit. A model based on Mie theory is established to explain the
      experimental results. The LCORR takes advantage of the high sensitivity, small
      footprint, and low sample consumption with the ring resonator, as well as the
      efficient fluidic sample delivery with the capillary, and will open an avenue to
      future multiplexed sensor array development.

PMID- 16642099
TI  - Nanoscale metal waveguide arrays as plasmon lenses.
AB  - Propagation of surface plasmon polaritons (SPPs) through a set of nanoscale metal
      waveguide arrays (MWGAs) is numerically simulated by using the finite-difference
      time-domain method. The results reveal that MWGAs show an interesting lens effect
      on SPPs: SPPs can be strongly focused or defocused by the MWGAs, which we
      attribute to anomalous coupling of SPPs in MWGAs. Our results imply interesting
      potential for MWGAs in, for example, nonlinear optics, optical imaging, and
      nanosensing.

PMID- 16642100
TI  - Rows of optical vortices from elliptically perturbing a high-order beam.
AB  - An optical vortex (phase singularity) with a high topological strength resides on
      the axis of a high-order light beam. The breakup of this vortex under elliptic
      perturbation into a straight row of unit-strength vortices is described. This
      behavior is studied in helical Ince-Gauss beams and astigmatic, generalized
      Hermite-Laguerre-Gauss beams, which are perturbations of Laguerre-Gauss beams.
      Approximations of these beams are derived for small perturbations, in which a
      neighborhood of the axis can be approximated by a polynomial in the complex
      plane: a Chebyshev polynomial for Ince-Gauss beams, and a Hermite polynomial for
      astigmatic beams.

PMID- 16642101
TI  - Tunable light source for coherent anti-Stokes Raman scattering microspectroscopy
      based on the soliton self-frequency shift.
AB  - We present a photonic crystal fiber (PCF)-based light source for generating
      tunable excitation pulses (pump and Stokes) that are applicable to coherent anti
      Stokes Raman scattering (CARS) microspectroscopy. The laser employed is an
      unamplified Ti:sapphire femtosecond laser oscillator. The CARS pump pulse is
      generated by spectral compression of a laser pulse in a PCF. The Stokes pulse is
      generated by redshifting a laser pulse in a PCF through the soliton self
      frequency shift. This setup allows for probing up to 4000 cm(-1) with a spectral
      resolution of approximately 25 cm(-1). We characterize the stability and
      robustness of CARS microspectroscopy employing this light source.

PMID- 16642102
TI  - Coherent control of laser-induced breakdown.
AB  - We demonstrate coherent control of laser-induced optical breakdown in Ar and Xe
      with a femtosecond time-scale pulse train. By using a genetic algorithm to set
      the relative phases of seven optical sidebands that span two octaves of
      bandwidth, we enhance or suppress the probability of breakdown, vary the onset
      time of the spark, and to some extent, vary the position of the spark and the
      timing of the laser-produced shock wave.

PMID- 16642103
TI  - Analysis and design of nonlinear fiber Bragg gratings and their application for
      optical compression of reflected pulses.
AB  - We demonstrate a novel split-step solution for analyzing nonlinear fiber Bragg
      gratings. The solution is used for designing nonlinear fiber Bragg gratings with
      a low reflectivity. The structure of the grating is designed according to the
      profiles of the incident and reflected pulses. We demonstrate our method for
      nonlinear compression of a pulse reflected from a fiber Bragg grating. The method
      allows us to obtain compressed pulses with a very low wing intensity.

PMID- 16642104
TI  - Tapered semiconductor amplifiers for optical frequency combs in the near
      infrared.
AB  - A tapered semiconductor amplifier is injection seeded by a femtosecond optical
      frequency comb at 780 nm from a mode-locked Ti:sapphire laser. Energy gains of
      more than 17 dB(12 dB) are obtained for 1 mW(20 mW) of average input power when
      the input pulses are stretched into the picosecond range. A spectral window of
      supercontinuum light generated in a photonic fiber has also been amplified.
      Interferometric measurements show sub-Hertz linewidths for a heterodyne beat
      between the input and amplified comb components, yielding no detectable phase
      noise degradation under amplification. These amplifiers can be used to boost the
      infrared power in f-to-2f interferometers used to determine the carrier-to
      envelope offset frequency, with clear advantages for stabilization of octave
      spanning femtosecond lasers and other supercontinuum light sources.

PMID- 16642105
TI  - Generation of ten-cycle pulses from an ytterbium fiber laser with cubic phase
      compensation.
AB  - We demonstrate the use of a prism-grating sequence to reduce third-order
      dispersion inside a mode-locked Yb fiber laser. This laser generates pulses as
      short as 33 fs with extremely clean temporal and spectral profiles. Nanojoule
      pulse energies are possible.

PMID- 16642106
TI  - Discrete negative refraction in photonic crystal waveguide arrays.
AB  - We report a systematic analysis of anomalous refractive effects at interfaces
      between two photonic crystal waveguide arrays. Discrete negative refraction can
      be easily predicted from the sign of the coupling coefficient between adjacent
      waveguides, regardless of handedness of propagation.

PMID- 16642107
TI  - Photothermally enabled lithography for refractive-index modulation in SU-8
      photoresist.
AB  - We present a new lithographic technique based on a hybrid photothermal process to
      modulate the refractive index in commercial SU-8 photoresist. Owing to a
      difference in cross-linking, the refractive index of unexposed SU-8 cross-linked
      by thermally induced polymerization is 0.0072 higher than that of SU-8 cross
      linked by UV exposure and postbaking. Making use of this property, we fabricated
      two thick, flat-topped index-modulated diffractive optical elements (DOEs) that
      contain different phase distributions and measured their wavefront
      reconstruction. The good experimental reconstructions of the index DOEs
      demonstrate the potential to extend the refractive-index modulation technique for
      the fabrication of three-dimensional optical elements without needing a
      development step.

PMID- 16642108
TI  - Fabrication of a pure polarization grating in a cross-linked azopolymer by
      polarization-modulated holography.
AB  - A cross-linked azopolymer with high optical and thermal stability was prepared. A
      pure polarization grating without surface topology was fabricated from cross
      linked azopolymer by polarization holography by use of orthogonal linearly
      polarized beams from a He-Cd laser with a power density of 60 mW/cm(-2). The
      surface relief structure was investigated by atomic-force microscopy, and the
      polarization grating was observed by polarization optical microscopy. The grating
      spacing is 1.5 microm. The grating is stable at room temperature and can endure
      repeated writing-erasing.

PMID- 16642109
TI  - Hollow polycarbonate fiber for Er:YAG laser light delivery.
AB  - We developed hollow fibers with polycarbonate (PC) capillaries for use as a
      supporting tube. The PC capillaries were prepared by using a glass-drawing
      technique. Hollow PC fibers are safer and more flexible than hollow glass fibers
      because no fragments are released when the fibers are broken in various
      applications. Inner coating layers of silver and cyclic olefin polymer (COP)
      enhanced the reflection rate at the Er:YAG laser light wavelength. Using these
      fibers, we attained low loss for Er:YAG laser light transmission. By adjusting
      the drawing temperature in the fabrication of the PC capillaries, we created a
      smooth inner surface and uniform PC capillaries. We also demonstrated low-loss
      properties for visible pilot beams.

PMID- 16642110
TI  - 10 Gbit/s all-optical non-return to zero-return-to-zero data format conversion
      based on a backward dark-optical-comb injected semiconductor optical amplifier.
AB  - By using a semiconductor optical amplifier backward injected by a dark-optical
      comb pulse train at 10 GHz, we demonstrate a 10 Gbit/s all-optical nonreturn-to
      zero (NRZ) to return-to-zero (RZ) format conversion of an incoming optical
      pseudorandom binary sequence (PRBS) data stream. Both the polarity and the
      wavelength of data are conserved during format conversion. Without any pre
      amplification, the extinction ratio of degraded optical NRZ PRBS data is greatly
      improved from 7.13 to 13.6 dB after NRZ-to-RZ conversion. An ultralow bit-error
      rate of 10(-12) at a data rate as high as 10 Gbits/s is obtained with a received
      optical power of -18.3 dBm. The converted RZ PRBS data exhibit a negative power
      penalty of >3.7 dB compared with the NRZ PRBS data at a bit-error rate of 10(
      12).

PMID- 16642111
TI  - Polarization modulation instability in photonic crystal fibers.
AB  - Polarization modulation instability (PMI) in birefringent photonic crystal fibers
      has been observed in the normal dispersion regime with a frequency shift of 64
      THz between the generated frequencies and the pump frequency. The generated
      sidebands are orthogonally polarized to the pump. From the observed PMI frequency
      shift and the measured dispersion, we determined the phase birefringence to be
      5.3 x 10(-5) at a pump wavelength of 647.1 nm. This birefringence was used to
      estimate the PMI gain as a function of pump wavelength. Four-wave mixing
      experiments in both the normal and the anomalous dispersion regimes generated PMI
      frequency shifts that show good agreement with the predicted values over a 70 THz
      range. These results could lead to amplifiers and oscillators based on PMI.

PMID- 16642112
TI  - Dual-stage soliton compression of a self-started additive pulse mode-locked
      erbium-doped fiber laser for 48 fs pulse generation.
AB  - A dual-stage single-mode fiber (SMF) and large-effective-area fiber (LEAF) link
      for generating 48 fs pedestal-free pulses from a 40 MHz self-started additive
      pulse mode-locked erbium-doped fiber laser (APM-EDFL) with output peak power and
      pulse energy of 16 kW and 500 pJ, respectively, is demonstrated. With the
      SMF+LEAF link, a maximum pulse-width compression ratio of 7 and an optimized
      pulse-energy confining ratio of up to 85% can be achieved, and the soliton self
      frequency shift effect of the APM-EDFL pulse can be greatly suppressed.

PMID- 16642113
TI  - Suppression of phase error in differential phase-shift keying data by amplitude
      regeneration.
AB  - A regenerator for differential phase-shift keying data, consisting of two Mach
      Zehnder interferometers and two amplitude regenerators, is examined
      theoretically. The result, which shows that the phase error is suppressed if
      phase-preserving amplitude regenerators are used, provides a theoretical
      description of an already experimentally implemented regenerator.

PMID- 16642114
TI  - Three-level neodymium fiber laser incorporating photonic bandgap fiber.
AB  - We report a neodymium fiber laser incorporating an all-solid photonic bandgap
      fiber to suppress the four-level laser transition 4F(3/2)-4I(11/2). We
      demonstrate lasing at 907 nm on the three-level transition 4F(3/2)-4I(9/2) when
      pumping at 808 nm. The maximum slope efficiency obtained was 32% with a threshold
      pump power of 70 mW.

PMID- 16642115
TI  - In-line fiber optic structures for environmental sensing applications.
AB  - Fiber optic sensors based on the interaction of surface plasmons or evanescent
      waves with the surrounding environment are usually obtained by tapering an
      optical fiber, which significantly weakens the structure, or by use of just the
      end of the optical fiber. A fiber optic structure that maintains the structural
      integrity of the optical fiber with a long environmental interaction length is
      presented. Graded-index optical fiber elements are used as lenses, and a coreless
      optical fiber acts as the environmental interaction area. These elements are
      fused by an optical fiber splicer and result in a continuous fiber optic sensing
      system.

PMID- 16642116
TI  - Radial Hilbert transform with Laguerre-Gaussian spatial filters.
AB  - We analyze the point spread function (PSF) of the image processing system for
      radial Hilbert transform and propose a novel spiral phase filter, called the
      Laguerre-Gaussian spatial filter (LGSF). Theoretical analysis and real
      experiments show that the LGSF possesses some advantages in comparison with the
      conventional spiral phase plate (SPP). For example, the PSF of the imaging system
      with a LGSF presents smaller suboscillations than that with the conventional SPP,
      which allows us to realize a radial Hilbert transform for achieving a high
      contrast edge enhancement with high resolution.

PMID- 16642117
TI  - Laser-printer computer-generated holograms exhibiting suppressed higher orders in
      the replay field.
AB  - Conventional computer-generated holograms (CGHs) consist of regularly spaced
      square pixels, which, when replayed, exhibit many repeated higher orders.
      Furthermore, such pixellated CGHs are not well suited to printing using a
      conventional laser printer. In this Letter a novel method is presented that
      exploits the characteristics of a conventional laser-printing process to generate
      holograms with replay fields that exhibit markedly suppressed higher orders.

PMID- 16642118
TI  - Phase signature for particle detection with digital in-line holography.
AB  - The spatial phase resulting from the digital reconstruction of an in-line
      hologram of a particle field is shown to yield a unique pattern that can be used
      for particle detection. This phase signature is present only when viewed along
      with the reference light. The existence of the phase pattern is verified
      computationally and confirmed in laboratory experiments with holograms of
      calibrated glass spheres. The phase signature provides an alternative to the
      widely used intensity method for particle detection.

PMID- 16642119
TI  - Two-dimensional imaging of atomic distribution morphology created by
      holographically induced mass transfer of monomer molecules and nanoparticles in a
      silica-nanoparticle-dispersed photopolymer film.
AB  - We report an electron-probe microanalysis of a hologram recorded in a silica
      nanoparticle-dispersed photopolymer film. We used S and Si atoms as label
      elements to identify formed polymer and nanoparticle species, respectively. It is
      found that the periodic density distributions of S and Si atoms are out of phase
      with each other, indicating that those of the formed polymer and nanoparticles
      are out of phase each other. This result shows decisive evidence of the mutual
      diffusion of monomer molecules and silica nanoparticles in the film under
      holographic two-beam interference exposure.

PMID- 16642120
TI  - Quantitative phase-contrast microscopy by a lateral shear approach to digital
      holographic image reconstruction.
AB  - Combining the concept of lateral shear interferometry (LSI) within a digital
      holography microscope, we demonstrate that it is possible to obtain quantitative
      optical phase measurement in microscopy by a new single-image-processing
      procedure. Numerical lateral shear of the reconstructed wavefront in the image
      plane makes it possible to retrieve the derivative of the wavefront and remove
      the defocus aberration term introduced by the microscope objective. The method is
      tested to investigate a silicon structure and a mouse cell line.

PMID- 16642121
TI  - Photorefractive polymer device with video-rate response time operating at low
      voltages.
AB  - The high-voltage bias required for video-rate compatible, efficient operation of
      a photorefractive polymer composite is reduced from 6-8 to 1.3 kV. At this low
      voltage, the device can hold erasable Bragg holograms with 80% efficiency in
      addition to having a video-rate response time. The transition of the hologram's
      state from thick to thin is analyzed in detail.

PMID- 16642122
TI  - Estimation of the vanishing point in camera-mirror scenes from video.
AB  - Knowledge of the position of the vanishing point is the key for geometrical
      modeling of an image containing a reflective surface or cast shadows. Such an
      image can be analyzed as two subimages that constitute a stereo pair. For this
      model-estimation task an automatic method is presented that utilizes motion
      statistics and the statistical properties of image points for the determination
      of point correspondence and the subsequent estimation of vanishing point
      position, optimized by use of a goodness-of-fit function. We show that this
      approach gives robust results in widely different real-world environments, even
      when the correspondence is corrupted with considerable amounts of noise.

PMID- 16642123
TI  - Two-step phase-shifting interferometry and its application in image encryption.
AB  - Conventional phase-shifting interferometry (PSI) needs at least three
      interferograms. A novel algorithm of two-step PSI, with an arbitrary known phase
      step, by which a complex object field can be reconstructed with only two
      interferograms is proposed. This algorithm is then applied to an information
      security system based on double random-phase encoding in the Fresnel domain. The
      feasibility of this method and its robustness against occlusion and additional
      noise attacks are verified by computer simulations. This approach can
      considerably improve the efficiency of data transmission and is very suitable for
      Internet use.

PMID- 16642124
TI  - Coherent anti-Stokes Raman scattering imaging with a laser source delivered by a
      photonic crystal fiber.
AB  - We demonstrate laser-scanning coherent anti-Stokes Raman scattering (CARS)
      imaging with two excitation laser beams delivered by a large-mode-area photonic
      crystal fiber. The group-velocity dispersion and self-phase modulation effects
      are largely suppressed due to the large mode area of the fiber and the use of
      picosecond pulses. The fiber delivery preserves the signal level and image
      spatial resolution well. High-quality images of live spinal cord tissues are
      acquired using the fiber-delivered laser source. Our method provides a basic
      platform for developing a flexible and compact CARS imaging system.

PMID- 16642125
TI  - Remote temperature retrieval from heating or cooling targets.
AB  - We propose a simple pyrometric algorithm to retrieve the temperature from a
      radiating body during heating or cooling with no prior knowledge of the spectral
      emissivity. We ratio the measured fluxes at two different temperatures in two
      narrow bands. The error budget of this method is calculated. We consider its
      application for the rover-based exploration of the Martian ground, which is
      subjected to daily and seasonal temperature variations. The method is optimized
      to increase accuracy in the retrieval of temperature variation, which is the most
      interesting parameter for ground heat-flux studies.

PMID- 16642126
TI  - Evanescent-wave optical Cr VI sensor with a flexible fused-silica capillary as a
      transducer.
AB  - A light-guiding, flexible fused-silica (FFS) capillary has been used in designing
      an optical fiber Cr VI sensor for monitoring Cr VI ions in water samples. The FFS
      capillary is similar to a conventional silica optical fiber in that it can guide
      light in the wavelength region from the UV to the near IR but different from a
      conventional optical fiber in that it is a tubular waveguide. The inner surface
      of the FFS capillary is fused silica, which one can modify to design an optical
      fiber chemical sensor. The FFS capillary has a cladding layer plus a protective
      polymer coating on its outside surface. The cladding layer ensures the ability of
      the FFS capillary to guide light. The protective coating increases the FFS
      capillary's mechanical strength and makes it robust for practical applications.
      Compared with conventional silica optical fibers, it is much easier and more
      feasible to use this FFS capillary to fabricate long-path (tens of meters to
      thousands of meters) evanescent-wave based chemical sensors. We describe a Cr VI
      sensor based on the intrinsic evanescent-wave absorption by Cr VI ions in a water
      sample filled inside the capillary as an example of use of a FFS capillary in
      chemical sensor design. This simple sensor, using a 30 m light-guiding FFS
      capillary as a transducer, has the capability of detecting as little as 31 parts
      in 10(9) of Cr VI in a water sample, which is close to the detection limit of
      some sophisticated, expensive analytical instruments.

PMID- 16642127
TI  - Disorder-induced losses in planar photonic crystals.
AB  - The phenomenological approach introduced by Benisty [Appl. Phys. Lett. 76, 532
      (2000)] to model out-of-plane radiation losses in planar photonic crystals with a
      low vertical refractive index contrast is extended to the case of in-plane
      disorder. The model is experimentally validated by means of optical measurements
      on GaAs-based structures. For the present fabrication techniques the disorder
      induced contribution is found to be negligible compared with the other loss
      mechanisms.

PMID- 16642128
TI  - Low-loss and highly polarized emission from planar polymer waveguides.
AB  - The waveguiding properties and amplified spontaneous emission (ASE) of a blend of
      light-emitting gain-conjugated polymers were investigated. ASE-induced line
      narrowing occurs for excitation fluences larger than 100 microJ cm(-2), with a
      maximum optical-gain coefficient of 8 cm(-1). Energy transfer between the host
      and guest polymers, significantly reducing the self-absorption, leads to a loss
      coefficient of the waveguide as low as 0.3 cm(-1), which is believed to be the
      lowest value reported for active organic gain slabs and a highly polarized
      emission, with a polarization contrast up to 0.65. These results indicate that
      gain-conjugated polymer blends are state-of-the-art organic materials for lasing
      devices.

PMID- 16642129
TI  - Laser threshold of Mie resonances.
AB  - We show that time-independent scattering coefficients calculated from the
      standard extrapolation of Mie theory to the gain regime have physical meaning up
      to the laser threshold. The theoretical width of a resonance decreases linearly
      with increasing gain and becomes zero at the laser threshold. We performed
      experiments on dielectric microspheres with gain, trapped with optical tweezers.
      The width of the mode was measured to narrow as a function of the gain up to the
      lasing threshold, confirming both the validity of the extrapolation of Mie theory
      to the gain regime below threshold and our interpretation of its point of
      divergence as the laser threshold.

PMID- 16642130
TI  - Diode-pumped continuous-wave Nd:LuVO4 laser operating at 916 nm.
AB  - We realized an efficient diode-pumped Nd:LuVO4 continuous-wave (CW) laser
      operating at 916 nm. Laser experiments with 0.5 at. % Nd-doped Nd:LuVO4 crystals
      of various lengths and cutting directions were also investigated. The maximum
      output power of 930 mW was obtained with a slope efficiency of 27.2% and an
      optical conversion efficiency of 20.8% at the absorbed pump power of 4.5 W. The
      laser experiment shows that Nd:LuVO4 crystal can be used for an efficient diode
      pumped laser system.

PMID- 16642131
TI  - Tunable continuous-wave operation of a Cr3+,Li+:Mg2SiO4 laser.
AB  - Room-temperature tunable cw laser oscillation of Cr3+ ions in forsterite crystals
      (Mg2SiO4) codoped with chromium and lithium has been demonstrated, for the first
      time to the authors' knowledge, in pumping a crystal with a Ti:sapphire laser
      into the first excited level of Cr3+ ions (4A2-4T2 transition). The laser is
      smoothly tunable in the region of 1095-1170 nm. A slope efficiency as great as
      4.4% has been achieved.

PMID- 16642132
TI  - Embedded birefringent computer-generated holograms fabricated by femtosecond
      laser pulses.
AB  - Birefringent computer-generated holograms are fabricated in bulk fused silica by
      tight focusing of infrared femtosecond laser pulses. The polarization properties
      of the elliptically polarized diffracted light are in excellent agreement with
      the theoretical model. We experimentally demonstrate that for such birefringent
      structures the signal-to-noise ratio increases by approximately 9 dB when
      polarization filtering is used to suppress the undiffracted beam.

PMID- 16642133
TI  - Quantum-dot-based saturable absorber for femtosecond mode-locked operation of a
      solid-state laser.
AB  - A quantum-dot-based saturable absorber has been demonstrated to initiate the
      generation of femtosecond pulses from a passively mode-locked solid-state laser.
      Control and tuning of the pulse duration from 58 ps to 158 fs was achieved. The
      158 fs transform-limited pulses at 1280 nm are the shortest pulses that were
      produced from the Cr:forsterite laser passively mode locked by an InAs/InGaAs
      quantum-dot semiconductor saturable absorber mirror.

PMID- 16642134
TI  - Exact analytical solution for the vector electromagnetic field of Gaussian,
      flattened Gaussian, and annular Gaussian laser modes.
AB  - The exact vector integral solution for all the electromagnetic field components
      of a general flattened Gaussian laser mode is derived by using the angular
      spectrum method. This solution includes the pure and annular Gaussian modes as
      special cases. The integrals are of the form of Gegenbauer's finite integral and
      are computed analytically for each case, yielding fields satisfying the Maxwell
      equations exactly in the form of quickly converging Fourier-Gegenbauer series.

PMID- 16642135
TI  - Residual pump light as a probe of self-pulsing instability in an ytterbium-doped
      fiber laser.
AB  - Self-pulsing instability in the ytterbium-doped fiber (YDF) laser is investigated
      with the pump-bypassed cavity configuration. The residual pump light acts as a
      probe of the intracavity dynamics, and the temporal behavior of the light shows
      correlations with the self-mode locking instability in the original cavity and
      the sustained self-pulsing instability in the modified cavity of the YDF laser.
      The results suggest that the interactions among stimulated emission, pump
      absorption and/or reabsorption could account for self-pulsing instability in the
      YDF laser. The pump-bypassed laser cavity configuration can be used to
      investigate the instabilities of various kinds of fiber lasers.

PMID- 16642136
TI  - Stable coherent coupling of laser diodes by a volume Bragg grating in
      photothermorefractive glass.
AB  - Two separate laser diodes emitting near 980 nm were coupled by a thick volume
      Bragg grating recorded in a photothermorefractive glass. The coupled diodes
      emitted at the same wavelength with a spectral width narrowed to below the
      resolution of the spectrum analyzer (<30 pm). Coherent emission at a pumping
      level greater than five times above the threshold was observed for several months
      with near-unity visibility of the interference pattern.

PMID- 16642137
TI  - Generation of 10(11) contrast 50 TW laser pulses.
AB  - We demonstrate what we believe to be the highest-contrast (10(11)),
      multiterawatt, chirped-pulse amplification (CPA) Ti:sapphire laser by applying
      the modified cross-polarized-wave (XPW) generation method. This method produces a
      contrast improvement of 3 orders of magnitude using microjoule input energy.
      Microjoule energy can be achieved by direct amplification without the
      complications of a double CPA system. The 10(11) contrast is sufficient for
      experiments on high-damage-threshold solid targets with focused intensities up to
      10(22) W/cm(2).

PMID- 16642138
TI  - Origin of low-coherence enhanced backscattering.
AB  - The origin of low-coherence enhanced backscattering (EBS) of light in random
      media when the spatial coherence length of illumination is much smaller than the
      transport mean free path has been poorly understood. We report that in weakly
      scattering discrete random media low-coherence EBS originates from time-reversed
      paths of double scattering. Low spatial coherence illumination dephases the time
      reversed waves outside its finite coherence area, which isolates the minimal
      number of scattering events in EBS from higher-order scattering. Moreover, we
      show the first experimental evidence that the minimal number of scattering events
      in EBS is double scattering, which has been hypothesized since the first
      observation of EBS.

PMID- 16642139
TI  - Full-field swept-source phase microscopy.
AB  - We present a full-field phase microscopy technique for quantitative nanoscale
      surface profiling of samples in reflection. This technique utilizes swept-source
      optical coherence tomography in a full-field common path interferometer for phase
      stable cross-sectional acquisition without scanning. Subwavelength variations in
      surface sample features are measured without interference from spurious
      reflections by processing the interferometric phase at a selected depth plane,
      providing a 1.3 nm stability for high signal-to-noise ratio surface features.
      Nanoscale imaging was demonstrated by measuring the location of receptor sites on
      a DNA assay biochip and the surface topography of erythrocytes in a blood smear.

PMID- 16642140
TI  - Condenser for Koehler-like illumination in transmission x-ray microscopes at
      undulator sources.
AB  - We report on a novel condenser for full-field transmission x-ray microscopes that
      use synchrotron radiation from an undulator source. The condenser produces a
      Koehler-like homogeneous intensity distribution in the sample plane and
      eliminates object illumination problems connected with the high degree of spatial
      coherence in an undulator beam. The optic consists of a large number of small
      linear diffraction gratings and is therefore relatively easy to manufacture.
      First imaging experiments with a prototype condenser were successfully performed
      with the Twinmic x-ray microscope at the Elettra synchrotron facility in Italy.

PMID- 16642141
TI  - Electro-optical microscopy: mapping nonlinear polymer films with micrometric
      resolution.
AB  - The first demonstration, to the best of our knowledge, of electro-optical
      microscopy is presented and applied to a polymer-based optical device. A confocal
      transmission microscope with interferometric homodyne detection is implemented to
      measure Pockels phase shifts with micrometric spatial resolution and an accuracy
      level down to 4 x 10(-7) rad. This technique is applied to poled polymer films in
      which noncentrosymmetric molecular orientation is preliminarily achieved in the
      sample plane between transverse planar electrodes. The electro-optic mapping of
      this structure exhibits nonuniform and asymmetric patterns of the nonlinear
      response that are characteristic of the poling spatial inhomogeneity as confirmed
      by second-harmonic generation microscopy.

PMID- 16642142
TI  - Double-clad photonic crystal fiber coupler for compact nonlinear optical
      microscopy imaging.
AB  - A 1 x 2 double-clad photonic crystal fiber coupler is fabricated by the fused
      tapered method, showing a low excess loss of 1.1 dB and a splitting ratio of 97/3
      over the entire visible and near-infrared wavelength range. In addition to the
      property of splitting the laser power, the double-clad feature of the coupler
      facilitates the separation of a near-infrared single-mode beam from a visible
      multimode beam, which is ideal for nonlinear optical microscopy imaging. In
      conjunction with a gradient-index lens, this coupler is used to construct a
      miniaturized microscope based on two-photon fluorescence and second-harmonic
      generation. Three-dimensional nonlinear optical images demonstrate potential
      applications of the coupler to compact all-fiber and nonlinear optical microscopy
      and endoscopy.

PMID- 16642143
TI  - Reciprocity in scanning near-field optical microscopy: illumination and
      collection modes of transmission measurements.
AB  - We experimentally investigated the reciprocity of scanning near-field optical
      microscopy between illumination and collection modes. Near-field transmission
      images of single gold spheres and nanorods observed by the two modes are found to
      be equivalent to each other in the region from visible to near infrared. This
      result shows that reciprocity holds for the near-field scattering problems. We
      found that the conventional optical selection rule for far-field excitations does
      not apply not only under illumination mode but also with collection-mode
      arrangements. The possible origin of this observation might be the near-field
      probe.

PMID- 16642144
TI  - Resolution enhancement in a light-sheet-based microscope (SPIM).
AB  - Light-sheet-based microscopy [single-plane illumination microscope (SPIM)]
      performs very well at low numerical apertures. It complements conventional (FM),
      confocal (CFM), and two-photon fluorescence microscopy (2hnu-FM) currently used
      in modern life sciences. Lateral and axial SPIM point spread function (PSF)
      extents are measured by using fluorescent beads to determine the 3D resolution.
      The results are compared with values derived from an analytical theory and
      numerical simulations. The discrepancies are found to be less than 5%. The axial
      extent of a SPIM-PSF (10x/0.3 W) is approximately 5.7 microm. This value is
      almost a factor of 2 smaller than in CFM, more than 2.5 times smaller than in FM,
      and more than three times smaller than in 2hnu-FM. SPIM outperforms 2hnu-FM and
      FM, while CFM has a better axial resolution at NAs above 0.8.

PMID- 16642145
TI  - All-optical switching and multifrequency generation in a dual-core photonic
      crystal fiber.
AB  - We demonstrate all-optical switching at 1550 nm between two weakly coupled cores
      in a photonic crystal fiber for intensities up to 0.5 TW/cm2. Spectrum analysis
      at higher intensities reveals that the output was dominated by continuum
      generation primarily towards shorter wavelengths.

PMID- 16642146
TI  - Multipole vector solitons in nonlocal nonlinear media.
AB  - We show that multipole solitons can be made stable via vectorial coupling in bulk
      nonlocal nonlinear media. Such vector solitons are composed of mutually
      incoherent nodeless and multipole components jointly inducing a nonlinear
      refractive index profile. We found that stabilization of the otherwise highly
      unstable multipoles occurs below certain maximum energy flow. Such a threshold is
      determined by the nonlocality degree.

PMID- 16642147
TI  - How to measure chi(3) of a nanoparticle.
AB  - Most of the known methods to measure the nonlinear optical properties of
      materials deal with the bulk properties, but there are many demanding
      applications that require those measurements to be done on a single particle or a
      single molecule. We report a novel application of nonlinear optics to measure the
      third-order nonlinear optical susceptibility of nanoparticles in solutions. By
      measuring the power of the third harmonic generated in a diluted solution of
      nanoparticles, both the size and chi(3) can be extracted from a simple set of
      measurements.

PMID- 16642148
TI  - Light propagation through a nonlinear defect: symmetry breaking and controlled
      soliton emission.
AB  - We investigate the emission of solitons at a nonlinear longitudinal defect. We
      discuss the basic physics and introduce a novel approach to achieve complete
      nonlinear control of the process. Theoretical results are confirmed by numerical
      simulations.

PMID- 16642149
TI  - Development of a quasi-phase-matched, second-harmonic generation periodically
      poled lithium niobate waveguide with an integrated electro-optical modulator.
AB  - A novel type of waveguide quasi-phase-matched device with output electro-optical
      (EO) modulation is proposed and demonstrated. The second-harmonic generated
      output can be modulated with a high extinction ratio by integration of dual EO
      phase modulators on a periodically poled lithium niobate waveguide. Blue and
      green coherent light with EO modulation was demonstrated, and wavelength
      dispersion of r33 is discussed.

PMID- 16642150
TI  - Nonlinear optical properties of glasses in the system Ge/Ga-Sb-S/Se.
AB  - We report n2 measurements of selected chalcogenide glasses using a modified Z
      scan technique. Measurements were made with picosecond pulses emitted by a 10 Hz
      Q-switched, mode-locked Nd:YAG laser at 1064 nm under conditions suitable to
      characterize ultrafast nonlinearities. The nonlinear index increases
      significantly up to 246 times the n2 for fused silica with an increase of SbS3
      units and also very slightly with the replacement of Ge by Ga or S by Se. We have
      attributed the variation of n2 to the total number of electronic lone pairs and
      to the position of the absorption band gap, which are induced by the presence of
      GaS4 units or Se-Se bonds in the glass structure.

PMID- 16642151
TI  - Demonstration of all-optical beam steering in modulated photonic lattices.
AB  - We demonstrate experimentally all-optical beam steering in modulated photonic
      lattices induced optically by three-beam interference in a biased photorefractive
      crystal. We identify and characterize the key physical parameters governing the
      beam steering and show that the spatial resolution can be enhanced by the
      additional effect of nonlinear beam self-localization.

PMID- 16642152
TI  - Raman lasing and cascaded coherent anti-Stokes Raman scattering of a two-phonon
      Raman band.
AB  - Raman lasing of a two-phonon Raman band in the anti-Stokes side is demonstrated.
      Two femtosecond light pulses with identical wavelengths are irradiated onto a
      SrTiO3 crystal in a cross-beam configuration. Under low excitation power, several
      wave-mixing signals with identical wavelengths are emitted. When the power
      exceeds a critical value, cascaded coherent anti-Stokes Raman scattering (CARS)
      signals are emitted, the frequency step of which is coincident with that of the
      strongest two-phonon Raman band of 2TO2.

PMID- 16642153
TI  - Incoherent and coherent writing and erasure of cavity solitons in an optically
      pumped semiconductor amplifier.
AB  - Cavity solitons in semiconductor amplifiers were, from the beginning of their
      study and observation, obtained either spontaneously or in a controlled manner by
      local coherent excitation. We describe two experiments that demonstrate coherent
      and, we believe for the first time, incoherent writing and erasure of cavity
      solitons in an optically pumped vertical-cavity semiconductor amplifier by short
      optical pulses.

PMID- 16642154
TI  - Counterpropagating spatial Kerr soliton in reflection gratings.
AB  - We analytically predict the existence of both spatial bright and dark
      counterpropagating solitons in a reflection grating in the presence of the Kerr
      nonlinearity. The basic trapping mechanism consists of a twofold balance where
      diffraction is compensated by self-focusing and reflection is altered by the
      nonlinear-induced interferometric grating. We find that, whenever the spectral
      soliton profile lies within the grating stop band, bright and dark solitons exist
      only if the mutual phase of the counterpropagating solitons is pi or 0,
      respectively.

PMID- 16642155
TI  - Enhanced second-harmonic generation for multiple wavelengths by defect modes in
      one-dimensional photonic crystals.
AB  - We present an effective design of aperiodically stacked layers of nonlinear
      material and air, sandwiched by two truncated photonic crystals, in terms of the
      simulation annealing method. The constructed structure can achieve multiple
      wavelength second-harmonic generation (SHG) at the preassigned wavelengths. We
      derive a general solution of SHG in 1D inhomogeneous systems and apply it to
      evaluate the SHG conversion efficiency. Numerical simulations show that the
      conversion efficiency of SHG can be significantly enhanced when the fundamental
      wave frequencies are assigned to the designed defect states.

PMID- 16642156
TI  - Media tilt tolerance of bit-based and page-based holographic storage systems.
AB  - Tilt tolerance of media is compared for bit-based and page-based holographic
      storage systems having an equal diffraction efficiency per bit detector, dynamic
      range of the medium, and surface recording density. We have formalized the
      diffraction efficiency degradation caused by aberrations of a reconstructing
      reference beam induced by tilt of the medium, using a coupled wave theory in the
      Fourier domain. The bit-based holographic storage system has a larger media tilt
      tolerance compared with a page-based system with relatively large page size.

PMID- 16642157
TI  - Hybrid optics for focusing ultrashort laser pulses.
AB  - We present a specially designed hybrid optics comprising refraction and
      diffraction effects for tight spatial and temporal focusing of ultrashort laser
      pulses. Both aims can be put into practice by having a high numerical aperture
      (NA=0.45) and low internal dispersion at the same time. We are presenting what we
      believe is the first experimental realization of such a hybrid short plus
      focusing optics. The focusing properties are compared with a commonly used
      microscope objective (20 X, NA = 0.45) in theory and experimentally.

PMID- 16642158
TI  - C-shaped nanoaperture-enhanced germanium photodetector.
AB  - We present a C-shaped nanoaperture-enhanced Ge photodetector that shows 2-5 times
      the photocurrent enhancement over that from a square aperture of the same area at
      1310 nm wavelength. We demonstrate the polarization dependence of the C-aperture
      photodetector over a wide wavelength range. Our experimental observation agrees
      well with finite-difference time-domain simulation results.

PMID- 16642159
TI  - Color correction in planar optics configurations.
AB  - Color correction in planar optics configurations can be achieved by resorting to
      gradient-index rather than uniform-refractive-index substrates. The basic
      configuration, principle of correction, and calculated and experimental results
      are presented. The results reveal that, with an appropriate refractive index
      distribution along the thickness of the substrates, the color can be corrected
      over a wavelength range up to 155 nm depending on incidence angles.

PMID- 16642160
TI  - Dividing a light beam into two beams of orthogonal polarizations by reflection
      and refraction at a dielectric surface.
AB  - Reflection and refraction of monochromatic light by an air-dielectric interface
      at an incidence angle below the Brewster angle can generate split beams of equal
      power and orthogonal polarizations under certain achievable conditions.
      Generation of photon streams of orthogonal polarizations, previously thought to
      be possible mainly by double refraction in anisotropic crystals, is achieved for
      an infinite set of input states that leads to a correspondingly infinite set of
      pairs of orthogonal output states. A bare substrate of PbTe is particularly
      suitable for this beam splitting function in the IR. However, use of a high
      refractive-index quarter-wave layer on a low-refractive-index substrate extends
      the operating range of this interesting device to a much wider spectral range
      including the visible.

PMID- 16642161
TI  - High-resolution surface plasmon resonance sensor based on linewidth-optimized
      nanohole array transmittance.
AB  - A high spectral resolution, 2D nanohole-array-based surface plasmon resonance
      sensor that operates at normal or near normal incidence--facilitating high
      spatial resolution imaging--is presented. The angular and spectral transmittance
      of the structure is modified from a Fano type to a pure Lorentzian line shape
      with a parallel and orthogonal polarizer-analyzer pair. This change leads to a
      linewidth narrowing that maximizes the sensor resolution, which we show to be of
      O(10(-5)) refractive index units (RIU). We estimate the potential of this system
      of O(10(-6)) RIU under optimal conditions.

PMID- 16642162
TI  - All-optical time-delay relay based on a bacteriorhodopsin film.
AB  - Using the property of dynamic complementary suppression modulated transmission of
      bacteriorhodopsin film, we propose and demonstrate an all-optical time-delay
      relay in an incoherent light system. The relay can last for a certain amount of
      time after the switch function of turn off (or turn on) is activated.
      Furthermore, the delay time can be adjusted by changing the lifetime of the M
      state and the intensities of blue and yellow beams.

PMID- 16642163
TI  - Terahertz demonstrations of effectively two-dimensional photonic bandgap
      structures.
AB  - We demonstrate effectively two-dimensional (2D) terahertz (THz) photonic bandgap
      (PBG) structures for transverse electromagnetic (TEM) mode propagation within
      metal parallel plate waveguides (PPWG). The 2D-PBG structures consisting of
      square arrays of dielectric cylinders were characterized by THz time-domain
      spectroscopy (THz-TDS). THz photonic bandgaps were observed, as determined by the
      160 mum lattice constant, the 65 mum diameter, and the dielectric constant of the
      cylinders. The experimental measurements were fitted with excellent agreement to
      2D theory, confirming that for TEM mode propagation, effectively 2D propagation
      experiments can be achieved within the bounded space of the PPWG.

PMID- 16642164
TI  - Quantum measurements of spatial conjugate variables: displacement and tilt of a
      Gaussian beam.
AB  - We consider the problem of measurement of optical transverse profile parameters
      and their conjugate variable. Using multimode analysis, we introduce the concept
      of detection noise modes. For Gaussian beams, displacement and tilt are a pair of
      transverse-profile conjugate variables. We experimentally demonstrate the optimal
      encoding and detection of these variables with a spatial homodyning scheme. Using
      higher-order spatial mode squeezing, we show the sub-shot-noise measurements for
      the displacement and tilt of a Gaussian beam.

PMID- 16642165
TI  - Remote time-resolved filament-induced breakdown spectroscopy of biological
      materials.
AB  - We report, for what we believe to be the first time, on the feasibility of remote
      time-resolved filament-induced breakdown spectroscopy (FIBS) of biological
      materials. The fluorescence from egg white and yeast powder, induced by
      femtosecond laser pulse filamentation in air, was detected in the backward
      direction with targets located 3.5 m away from the detection system. The
      remarkably distinct spectra of egg white and yeast allow us to propose that this
      technique, time-resolved FIBS, could be potentially useful for remote detection
      and identification of harmful biological agents.

PMID- 16642166
TI  - High-spectral-resolution coherent anti-Stokes Raman scattering with
      interferometrically detected broadband chirped pulses.
AB  - To achieve high-spectral-resolution multiplex coherent anti-Stokes Raman
      scattering (CARS), one typically uses a narrowband pump pulse and a broadband
      Stokes pulse. This is to ensure a correspondence between anti-Stokes and
      vibrational frequencies. We obtain high-resolution CARS spectra of isopropanol,
      using a broadband chirped pump pulse and a broadband Stokes pulse, by detecting
      the anti-Stokes pulse with spectral interferometry. With the temporally resolved
      anti-Stokes signal, we can remove the chirp of the anti-Stokes pulse and restore
      high spectral resolution while also rejecting nonresonant scattering.

PMID- 16642167
TI  - Optimum excitation conditions for the generation of high-electric-field terahertz
      radiation from an oscillator-driven photoconductive device.
AB  - We report the impulsive generation of terahertz (THz) radiation with a field
      amplitude of more than 1.5 kV/cm at megahertz repetition rates, using an
      interdigitated photoconducting device. The approach provides an average THz power
      of 190 microW, corresponding to an optical-to-THz conversion efficiency of 2.5 x
      10(-4). Optimum conditions are achieved when the excitation spot size is of the
      order of the THz wavelength.

PMID- 16642168
TI  - Extreme-ultraviolet spectral purity and magnetic ion debris mitigation by use of
      low-density tin targets.
AB  - We investigate the extreme-ultraviolet (EUV) emission from targets that contain
      tin as an impurity and the advantages of using these targets for ion debris
      mitigation by use of a magnetic field. The EUV spectral features were
      characterized by a transmission grating spectrograph. The in-band EUV emission
      energy was measured with a calorimeter of absolute calibration. The ion flux
      coming from the plume was measured with a Faraday cup. Our studies indicate that
      0.5% Sn density is necessary to obtain a conversion efficiency very close to that
      of full-density Sn. The use of Sn-doped low-Z targets provides a narrower
      unresolved transition array and facilitates better control of energetic ions in
      the presence of a moderate magnetic field of 0.64 T.

PMID- 16642169
TI  - Spectral phase control and temporal superresolution toward the single-cycle
      pulse.
AB  - The concept of temporal superresolution is applied to optical few-cycle laser
      pulses for the first time to our knowledge. Pulse durations of as little as to
      3.7 fs, well below the Fourier limit, are achieved by pulse shaping of an octave
      spanning Ti:sapphire oscillator spectrum. Our prism-based pulse shaper also
      enables us to generate a manifold of well-controlled pulse sequences that are
      important for coherent control applications on a femtosecond time scale.

PMID- 16642170
TI  - Efficient diode-pumped Yb3+:Y2SiO5 and Yb3+:Lu2SiO5 high-power femtosecond laser
      operation.
AB  - We report the mode-locked operation of two new Yb-doped oxyorthosilicates, Y2SiO5
      (YSO) and Lu2SiO5 (LSO), that are longitudinally diode pumped. Yb:YSO supplied
      pulses as short as 122 fs with 410 mW of output power at 1041 nm. More than 2.6 W
      of average output power, for pulse durations of 198 fs at 1044 nm and 260 fs at
      1059 nm for Yb:YSO and Yb:LSO, respectively, were provided. These are, to our
      best knowledge, the highest values ever obtained and the most efficient mode
      locked laser in such a classic fiber-coupled diode-pumping configuration.

PMID- 16642171
TI  - Design and characterization of extreme-ultraviolet broadband mirrors for
      attosecond science.
AB  - A novel multilayer mirror was designed and fabricated based on a recently
      developed three-material technology aimed both at reaching reflectivities of
      about 20% and at controlling dispersion over a bandwidth covering photon energies
      between 35 and 50 eV. The spectral phase upon reflection was retrieved by
      measuring interferences in a two-color ionization process using high-order
      harmonics produced from a titanium: sapphire laser. We demonstrate the
      feasibility of designing and characterizing phase-controlled broadband optics in
      the extreme-ultraviolet domain, which should facilitate the manipulation of
      attosecond pulses for applications.

PMID- 16642172
TI  - Phase-locked control of tiled-grating assemblies for chirped-pulse-amplified
      lasers using a Mach-Zehnder interferometer.
AB  - Multikilojoule petawatt lasers using chirped-pulse amplification are being
      constructed worldwide. Several systems have adopted a tiled-grating approach to
      meet the size requirements for the compression gratings. Grating tiles need to be
      precisely phased to ensure a transform-limited focal spot when focusing high
      energy laser pulses in the target plane. A computer-control test system that uses
      a Mach-Zehnder interferometer capable of monitoring and correcting drift in the
      tiled-grating assemblies within the compressor is described. The differential
      errors due to eight gratings, within a compressor with four grating assemblies,
      were compensated by adjusting a single grating.

PMID- 16642173
TI  - Single-element objective lens for soft x-ray differential interference contrast
      microscopy.
AB  - High-resolution soft x-ray differential interference contrast (DIC) imaging was
      demonstrated through the use of a single-element objective, the XOR pattern, in a
      full-field soft x-ray microscope. DIC images of the magnetic domains in a 59 nm
      thick amorphous Gd25Fe75 layer were obtained and magnetic phase contributions
      were directly imaged. With its elemental, chemical, and magnetic specificity,
      compatibility with various sample environments, and ease of implementation, we
      expect this soft x-ray DIC technique to become one of the standard modes of
      operation for existing full-field soft x-ray microscopes.

PMID- 16642174
TI  - Producing illumination-independent additively mixed colors by diffractive optics.
AB  - We apply transmission gratings under Littrow incidence to produce polychromatic
      colors by additive color mixing. Parametric optimization of gratings is employed
      to produce high efficiency. In addition, we show that the system can yield the
      same color from a wide variety of spectra; i.e., the system can produce metameric
      colors.

PMID- 16642175
TI  - Integration of local motion is normal in amblyopia.
AB  - We investigate the global integration of local motion direction signals in
      amblyopia, in a task where performance is equated between normal and amblyopic
      eyes at the single element level. We use an equivalent noise model to derive the
      parameters of internal noise and number of samples, both of which we show are
      normal in amblyopia for this task. This result is in apparent conflict with a
      previous study in amblyopes showing that global motion processing is defective in
      global coherence tasks [Vision Res. 43, 729 (2003)]. A similar discrepancy
      between the normalcy of signal integration [Vision Res. 44, 2955 (2004)] and
      anomalous global coherence form processing has also been reported [Vision Res.
      45, 449 (2005)]. We suggest that these discrepancies for form and motion
      processing in amblyopia point to a selective problem in separating signal from
      noise in the typical global coherence task.

PMID- 16642176
TI  - Postreceptoral chromatic-adaptation mechanisms in the red-green and blue-yellow
      systems using simple reaction times.
AB  - Simple visual-reaction times (VRT) were measured for a variety of stimuli
      selected along red-green (L-M axis) and blue-yellow [S-(L + M) axis] directions
      in the isoluminant plane under different adaptation stimuli. Data were plotted in
      terms of the RMS cone contrast in contrast-threshold units. For each opponent
      system, a modified Pieron function was fitted in each experimental configuration
      and on all adaptation stimuli. A single function did not account for all the
      data, confirming the existence of separate postreceptoral adaptation mechanisms
      in each opponent system under suprathreshold conditions. The analysis of the VRT
      hazard functions suggested that both color-opponent mechanisms present a well
      defined, transient-sustained structure at marked suprathreshold conditions. The
      influence of signal polarity and chromatic adaptation on each color axis proves
      the existence of asymmetries in the integrated hazard functions, suggesting
      separate detection mechanisms for each pole (red, green, blue, and yellow
      detectors).

PMID- 16642177
TI  - Reevaluation of color constancy algorithm performance.
AB  - The relative performance of color constancy algorithms is evaluated. We highlight
      some problems with previous algorithm evaluation and define more appropriate
      testing procedures. We discuss how best to measure algorithm accuracy on a single
      image as well as suitable methods for summarizing errors over a set of images. We
      also discuss how the relative performance of two or more algorithms should best
      be compared, and we define an experimental framework for testing algorithms. We
      reevaluate the performance of six color constancy algorithms using the procedures
      that we set out and show that this leads to a significant change in the
      conclusions that we draw about relative algorithm performance as compared with
      those from previous work.

PMID- 16642178
TI  - Pseudoscopic imaging in a double diffraction process with a slit: critical point
      properties.
AB  - Pseudoscopic (inverted depth) images that keep a continuous parallax were shown
      to be possible by use of a double diffraction process intermediated by a slit.
      One diffraction grating directing light to the slit acts as a wavelength encoder
      of views, while a second diffraction grating decodes the projected image. The
      process results in the enlargement of the image under common white light
      illumination up to infinite magnification at a critical point. We show that this
      point corresponds to another simple-symmetry object-observer system. Our
      treatment allows us to explain the experience by just dealing with main ray
      directions.

PMID- 16642179
TI  - Inverse scattering for optical coherence tomography.
AB  - Inverse scattering theory for optical coherence tomography (OCT) is developed.
      The results are used to produce algorithms to resolve three-dimensional object
      structure, taking into account the finite beam width, diffraction, and defocusing
      effects. The resolution normally achieved only in the focal plane of the OCT
      system is shown to be available for all illuminated depths in the object without
      moving the focal plane. Spatially invariant resolution is verified with numerical
      simulations and indicates an improvement of the high-resolution cross-sectional
      imaging capabilities of OCT.

PMID- 16642180
TI  - Inverse scattering and diffraction tomography in cylindrical background media.
AB  - A recently developed inverse scattering method based on the distorted-wave Born
      approximation (DWBA) that applies to objects embedded in known background media
      [Inverse Probl.19, 855 (2003);20, 1307 (2004)] is implemented for the special
      case of circularly symmetric scatterers embedded in circularly symmetric
      backgrounds. The newly developed scheme is applied in a computer-simulation study
      of optical diffraction tomography (ODT), and the results are compared and
      contrasted with reconstructions obtained using the filtered backpropagation
      algorithm (FBP algorithm). Unlike the DWBA-based inversion algorithm, the FBP
      algorithm does not take into account multiple scattering within the known
      background, and it is found that the newly implemented scheme yields
      reconstructions much superior to those obtained using the FBP algorithm. The
      research reported applies to a number of important applications that include
      ultrasound nondestructive evaluation testing of cylinders for defects as well as
      ODT.

PMID- 16642181
TI  - Automated determination of the center of rotation in tomography data.
AB  - Tomographic reconstruction requires precise knowledge of the position of the
      center of rotation in the sinogram data; otherwise, artifacts are introduced into
      the reconstruction. In parallel-beam microtomography, where resolution in the 1
      microm range is reached, the center of rotation is often only known with
      insufficient accuracy. We present three image metrics for the scoring of
      tomographic reconstructions and an iterative procedure for the determination of
      the position of the optimum center of rotation. The metrics are applied to model
      systems as well as to microtomography data from a synchrotron radiation source.
      The center of rotation is determined using the image metrics and compared with
      the results obtained by the center-of-mass method and by image registration. It
      is found that the image metrics make it possible to determine the axis position
      reliably at well below the resolution of one detector bin in an automated
      procedure.

PMID- 16642182
TI  - Circularly symmetric phase filters for control of primary third-order
      aberrations: coma and astigmatism.
AB  - A quartic phase retardation function is described that reduces the variation of
      the intensity of the focal point of incoherent imaging systems suffering from
      primary third-order aberrations limited to coma and astigmatism. Corresponding
      modulation transfer functions are shown to remain practically invariant for
      moderate amounts of coma and astigmatism.

PMID- 16642183
TI  - On representing and correcting wavefront errors in high-contrast imaging systems.
AB  - Conventional adaptive-optics systems correct the wavefront by adjusting a
      deformable mirror (DM) based on measurements of the phase aberration taken in a
      pupil plane. The ability of this technique, known as phase conjugation, to
      correct aberrations is normally limited by the maximum spatial frequency of the
      DM. In this paper we show that conventional phase conjugation is not able to
      achieve the dark nulls needed for high-contrast imaging. Linear combinations of
      high frequencies in the aberration at the pupil plane "fold" and appear as low
      frequency aberrations at the image plane. After describing the frequency-folding
      phenomenon, we present an alternative optimized solution for the shape of the
      deformable mirror based on the Fourier decomposition of the effective phase and
      amplitude aberrations.

PMID- 16642184
TI  - Modeling, simulation, and open-loop control of a continuous facesheet MEMS
      deformable mirror.
AB  - We introduce a coupled system of nonlinear partial differential equations (PDEs)
      to model a particular microelectromechanical systems (MEMS) deformable mirror
      consisting of a continuous facesheet coupled with electrostatic plate-driven
      actuators. To make the problem computationally tractable, we reduced the system
      to a single linear PDE for the facesheet coupled with nonlinear algebraic
      constraints for each of the actuators. We also introduce a nonlinearly
      constrained quadratic optimization problem for open-loop control of the MEMS
      mirror. Numerical simulation and control results are presented, and shortcomings
      of the model are discussed.

PMID- 16642185
TI  - Adaptive optics system for investigation of the effect of the aberration dynamics
      of the human eye on steady-state accommodation control.
AB  - It is now known that defocus is not the only aberration in the eye that exhibits
      dynamic behavior during fixation. It is currently unknown what effects, if any,
      the dynamics of these other aberrations have on steady-state accommodation
      control. We constructed an adaptive optics system to serve as a tool for future
      investigations in this area. The system has several design features of interest,
      including automated precompensation of defocus and astigmatism and a method to
      bypass a scanner used to reduce speckle. It also has the facility to measure the
      eye's aberrations independent of the aberration manipulation device-a 37-actuator
      membrane deformable mirror. Coherence function analysis was used to assess the
      deformable mirror performance in terms of coupling between Zernike modes. Modes
      beyond third radial order showed severe coupling. Pilot data were collected on
      one subject to demonstrate the utility of this system in steady-state
      accommodation studies. The value of the system for future work in this area is
      discussed.

PMID- 16642186
TI  - Increasing the lateral resolution of 4Pi fluorescence microscopes.
AB  - The axial resolution of fluorescence microscopes can be considerably improved by
      superposing two illumination beams and by adding coherently the two wavefronts
      emitted by the luminescent sample. This solution has been implemented in 4Pi
      microscopes. Theoretical and experimental results have shown that a considerable
      improvement of the axial resolution can be obtained with these microscopes.
      However, the lateral resolution remains limited by diffraction. We propose a
      configuration of a 4Pi microscope in which the lateral displacement of the source
      modifies the collection efficiency function (CEF). Numerical calculations based
      on an approximate scalar theory and on exact vector-wave-optics results of the
      field distribution of the electromagnetic field in image space show that the
      lateral extent of the CEF can be reduced by a factor greater than 2 with respect
      to the diffraction limit. We show that, with this solution, the resolution in the
      transverse plane of 4Pi type B and 4Pi type C microscopes can be improved
      significantly.

PMID- 16642187
TI  - Analysis of mode coupling due to spherical defects in ideal fully metal-coated
      scanning near-field optical microscopy probes.
AB  - We investigate the effect of defects in the metal-coating layer of a scanning
      near-field optical microscopy (SNOM) probe on the coupling of polarization modes
      using rigorous electromagnetic modeling tools. Because of practical limitations,
      we study an ensemble of simple defects to identify important trends and then
      extrapolate these results to more realistic structures. We find that a probe with
      many random defects will produce a small but significant coupling of energy
      between a linearly polarized input mode and a radial/longitudinal polarization
      mode, which is known to produce a strongly localized emitted optical field and is
      desirable for SNOM applications.

PMID- 16642188
TI  - Photon diffusion coefficient in scattering and absorbing media.
AB  - We present a unified derivation of the photon diffusion coefficient for both
      steady-state and time-dependent transport in disordered absorbing media. The
      derivation is based on a modal analysis of the time-dependent radiative transfer
      equation. This approach confirms that the dynamic diffusion coefficient is given
      by the random-walk result D = cl(*)/3, where l(*) is the transport mean free path
      and c is the energy velocity, independent of the level of absorption. It also
      shows that the diffusion coefficient for steady-state transport, often used in
      biomedical optics, depends on absorption, in agreement with recent theoretical
      and experimental works. These two results resolve a recurrent controversy in
      light propagation and imaging in scattering media.

PMID- 16642189
TI  - Mie scattering by an anisotropic object. Part I. Homogeneous sphere.
AB  - Establishing a vector spherical harmonic expansion of the electromagnetic field
      propagating inside an arbitrary anisotropic medium, we extend Mie theory to the
      diffraction by an anisotropic sphere, with or without losses. The particular case
      of a uniaxial material leads to a simpler analysis. This work opens the way to
      the construction of a differential theory of diffraction by a three-dimensional
      object with arbitrary shape, filled by an arbitrary anisotropic material.

PMID- 16642190
TI  - Mie scattering by an anisotropic object. Part II. Arbitrary-shaped object:
      differential theory.
AB  - The differential theory of diffraction by an arbitrary-shaped body made of
      arbitrary anisotropic material is developed. The electromagnetic field is
      expanded on the basis of vector spherical harmonics, and the Maxwell equations in
      spherical coordinates are reduced to a first-order differential set. When
      discontinuities of permittivity exist, we apply the fast numerical factorization
      to find the link between the electric field vector and the vector of electric
      induction, developed in a truncated basis. The diffraction problem is reduced to
      a boundary-value problem by using a shooting method combined with the S-matrix
      propagation algorithm, formulated for the field components instead of the
      amplitudes.

PMID- 16642191
TI  - Generalized groove density equation concerning bending-grating-related imaging
      properties.
AB  - Varied-line-spacing gratings are used in soft-x-ray monochromators and
      spectrometers because of their ability to correct various aberrations by varying
      the groove density. A curved grating blank in a Rowland circle mounting could
      eliminate primary aberrations. Bending a plane constant-groove-density grating
      into a desirable surface can eliminate higher-order aberrations as a result of
      the change in surface profile and groove density. This provides a simple means
      for improving the imaging properties. When used in a monochromator, the grating
      can be bent to different degrees to minimize aberrations at all wavelengths.
      General formulas concerning the transformations of groove function, groove
      density, and groove spacing are presented for the bending grating. Analytic
      results with a numerical example show the significant properties of the system.

PMID- 16642192
TI  - Vectorial approach to Huygens's principle for plane waves: circular aperture and
      zone plates.
AB  - A vectorial equation that describes the Huygens principle was reported, and an
      expression for the secondary-spherical-wave energy density was found. With a
      vectorial formulation, we performed an exact calculation for the relative axial
      intensity of the wave diffracted by an illuminated circular aperture. The off
      axis intensity in Fresnel's and Fraunhofer's approximations was calculated. The
      zone plate was also studied by vectorial formulation. We showed that with
      increasing number of rings, the intensity maxima magnify as (2n + 2)(2), their
      full widths decrease, their positions remain unchanged, and secondary maxima
      appear, in a behavior similar to that for diffraction gratings.

PMID- 16642193
TI  - Diffraction theory: application of the fast Fourier factorization to cylindrical
      devices with arbitrary cross section lighted in conical mounting.
AB  - The differential theory of diffraction by arbitrary cross-section cylindrical
      objects is developed for the most general case of an incident field with a wave
      vector outside the cross-section plane of the object. The fast Fourier
      factorization technique recently developed for studying gratings is generalized
      to anisotropic and/or inhomogeneous media described in cylindrical coordinates;
      thus the Maxwell equations are reduced to a first-order differential set well
      suited for numerical computation. The resolution of the boundary-value problem,
      including an adapted S-matrix propagation algorithm, is explained in detail for
      the case of an isotropic medium. Numerical applications show the capabilities of
      the method for resolving complex diffraction problems. The method and its
      numerical implementation are validated through comparisons with the well
      established multipole method.

PMID- 16642194
TI  - Rotational frequency shifts in partially coherent optical fields.
AB  - We study the frequency shifts taking place when a random, stationary optical
      field rotates with respect to an observer. The field is expanded in terms of
      fully coherent Laguerre-Gaussian basis modes, for which the rotational frequency
      shifts have been studied previously. We demonstrate the formalism by considering
      the spectrum of a Gaussian Schell-model field, and show that for a spatially
      highly incoherent field, significant spectral changes can be expected.

PMID- 16642195
TI  - Inverse source problem for partially polarized beams in turbulent media.
AB  - The propagation of a class of partially polarized beams though atmospheric
      turbulence is treated using the coherent-modes-decomposition approach. This
      approach allows specifying the properties of sources generating radiation with a
      narrow polarization distribution that could be employed in active polarimetric
      remote sensing applications.

PMID- 16642196
TI  - Terahertz interferometric and synthetic aperture imaging.
AB  - The stand-off imaging properties of a terahertz (THz) interferometric array are
      examined. For this application, the imaged object is in the near-field region
      limit of the imaging array. In this region, spherical and circular array
      architectures can compensate for near-field distortions and increase the field of
      view and depth of focus. Imaging of THz point sources is emphasized to
      demonstrate the imaging method and to compare theoretical predictions to
      experimental performance.

PMID- 16642197
TI  - High-resolution ab initio three-dimensional x-ray diffraction microscopy.
AB  - Coherent x-ray diffraction microscopy is a method of imaging nonperiodic isolated
      objects at resolutions limited, in principle, by only the wavelength and largest
      scattering angles recorded. We demonstrate x-ray diffraction imaging with high
      resolution in all three dimensions, as determined by a quantitative analysis of
      the reconstructed volume images. These images are retrieved from the three
      dimensional diffraction data using no a priori knowledge about the shape or
      composition of the object, which has never before been demonstrated on a
      nonperiodic object. We also construct two-dimensional images of thick objects
      with greatly increased depth of focus (without loss of transverse spatial
      resolution). These methods can be used to image biological and materials science
      samples at high resolution with x-ray undulator radiation and establishes the
      techniques to be used in atomic-resolution ultrafast imaging at x-ray free
      electron laser sources.

PMID- 16642198
TI  - Importance of scattering and absorption for the outcoupling efficiency in organic
      light-emitting devices.
AB  - The outcoupling of light in organic light-emitting devices is one of the limiting
      parameters for obtaining a high external efficiency. A simple geometrical model
      is presented that allows one to estimate the importance of optical parameters
      such as mirror reflectivity, scattering probability, and device structure. The
      model allows the derivation of analytical expressions for the outcoupling
      efficiency in some simplified cases.

PMID- 16642199
TI  - Estimation method for the light extraction efficiency of light-emitting elements
      with a rigorous grating diffraction theory.
AB  - The light extraction efficiency of a light-emitting element with microstructured
      surface is analyzed with a rigorous grating diffraction theory. The grating
      theory reveals an improvement of extraction efficiency due to diffraction of
      light by the surface microstructure. The simulation results show that the
      improvement of extraction efficiency is due mainly to the reflected diffraction
      rather than to the transmitted diffraction. A part of total-internal-reflection
      light is diffracted into directions at less than the critical angle. Extraction
      efficiency is improved by multiple reflection and diffraction of light in a high
      refractive-index layer. We propose a simple design method for an efficient
      surface microstructure from the viewpoint of reflected diffraction.

PMID- 16642200
TI  - Synthesis of multiple collinear helical modes generated by a phase-only element.
AB  - Phase-only elements are generally more desirable than complex-amplitude-modulated
      elements not only because of the higher diffraction efficiency but the readier
      implementation and fabrication. A novel iterative algorithm is proposed for
      generating multiple helical modes by a single phase-only element. A superposition
      of four helical modes is demonstrated experimentally by using a spatial light
      modulator.

PMID- 16642201
TI  - Iterative algorithm for subaperture stitching test with spherical
      interferometers.
AB  - Recently we have proposed an iterative algorithm for subaperture stitching
      interferometry. It was referred to as the subaperture stitching and localization
      (SASL) algorithm. The limitation of the algorithm is that three-dimensional
      Cartesian coordinates are required, whereas the standard spherical interferometer
      can read out only the phase differences on the pixels. On the basis of the SASL
      algorithm, we propose an iterative algorithm for a spherical subaperture
      stitching test. It deals with data directly from the spherical interferometer.
      Unknown radii of best-fit spheres for a null test of subapertures are included in
      the optimization variables. The developed algorithm inherits the advantages of
      the SASL algorithm.

PMID- 16642202
TI  - Improved-resolution digital holography using the generalized sampling theorem for
      locally band-limited fields.
AB  - We describe the recording conditions that, together with the appropriate
      numerical reconstruction process, permit high-lateral-resolution reconstruction
      of in-line digital holograms. By high resolution, we mean a resolution that is
      beyond the Nyquist frequency, which is achieved by common methods. The proposed
      method is based on a previously reported generalized sampling theory that
      presents the conditions to precisely reconstruct fields that in certain cases may
      be sampled with a sampling rate lower than the Nyquist rate. We examine the
      hologram-recording process in the Wigner space. On the basis of this analysis, we
      demonstrate a simple high-resolution numerical reconstruction method.

PMID- 16642203
TI  - Determining selected quadratic coefficients in noncentrosymmetric crystals.
AB  - We present a systematic theoretical examination concerning the practical
      possibility of measuring components of the quadratic symmetry tensors for solid
      materials lacking inversion symmetry. We show that information concerning the
      quadratic effects in noncentrosymmetrical crystals can be obtained directly by
      methods that allow for the bypassing of the coexisting dominant linear effects.
      Here, we deal only with the particular case of the electro-optic effect; however,
      the results and conclusions are also valid for the elasto-optic effects.

PMID- 16642204
TI  - THE EFFECTS OF 5-AZA-2'-DEOXYCYTIDINE (D-AZA) ON SONIC HEDGEHOG EXPRESSION IN
      MOUSE EMBRYONIC LIMB BUDS.
AB  - 5-Aza-2'-deoxycytidine (d-AZA) causes temporally-related defects in the mouse. At
      1.0 mg/kg on gestational day (GD) 10, d-AZA causes hindlimb phocomelia. Sonic
      hedgehog (Shh) plays a significant role in the normal development of limbs in
      rodent species. Sonic hedgehog peptides, found in the posterior mesenchyme of
      limb buds, are involved in patterning functions and in the regulation of both
      anterior-posterior polarity and proximal-distal outgrowth of the limb. The
      objective of the present study was to analyze alterations in Shh expression
      subsequent to d-AZA exposure. Pregnant mice were treated with d-AZA via
      intraperitonlal injection on GD 10. Controls were untreated. The reverse
      transcription-polymerase chain reaction (RT-PCR), whole mount in situ
      hybridization (ISH), and whole mount immunohistochemistry (WMI) were used to
      analyze expression patterns of Shh . For RT-PCR, embryonic hindlimb buds (buds)
      were taken 0, 4, 8, 12, or 24 hr after exposure. Cyclophilin was used as the
      baseline monitor. RNA was transcribed to cDNA and used as template with Shh
      specific primers for amplification. Whole embryos were collected 12 and 24 hr
      posttreatment for ISH. An antisense primer specific for Shh was used in an oligo
      based ISH protocol. Whole embryos were collected 36 and 48 hr posttreatment for
      WMI. The antibody corresponding to the amino terminal subunit of the Shh peptide
      was used. There was a treatment related up-regulation of Shh transcripts by 12
      and 24 hr posttreatment. The protein response of up-regulation was detectable by
      36 and 48 hr posttreatment. Our data suggest that 5-aza-2'-deoxycytidine-induced
      hindlimb defects may be associated with alterations in the level of Shh
      expression. This may be part of a cascade of signaling events involved in d-AZA
      induced hindlimb defects. Work is ongoing to determine the relationship of other
      gene species that may cooperate with Shh in the induction of the hindlimb
      defects.

PMID- 16642205
TI  - Potentiometric sensors for trace-level analysis.
AB  - This review summarizes recent progress in the development and application of
      potentiometric sensors with limits of detection (LODs) in the range 10(-8)-10(
      11) M. These LODs relate to total sample concentrations and are defined according
      to a definition unique to potentiometric sensors. LODs calculated according to
      traditional protocols (three times the standard deviation of the noise) yield
      values that are two orders of magnitude lower. We are targeting this article at
      analytical chemists who are non-specialists in the development of such sensors so
      that this technology may be adopted by a growing number of research groups to
      solve real-world analytical problems.We discuss the unique response features of
      potentiometric sensors and compare them to other analytical techniques,
      emphasizing that the choice of the method must depend on the problem of interest.
      We discuss recent directions in sensor design and development and present a list
      of 23 sensors with low LODs, with references. We give recent examples where
      potentiometric sensors have been used to solve trace-level analytical problems,
      including the speciation of lead and copper ions in drinking water, the
      measurement of free copper in sea water, and the uptake of cadmium ions by plant
      roots as a function of their speciation.

PMID- 16642206
TI  - [Significance of the expression of P53 protein and P21WAF1 protein in the gastric
      carcinoma tissues associated with Epstein-Barr virus (EBV) infections].
AB  - BACKGROUND: To study the difference in gene expression between the EBV associated
      gastric carcinoma (EBVaGC) tissues. To explore the mechanism of gastric carcinoma
      pathogenesis initiated by EBV. METHODS: In situ hybridization was used to study
      the frequencies of EBV small RNA expression in 155 cases of gastric carcinoma
      tissues. The expression levels of P53 protein and P21WAF1 protein were detected
      by immunohistochemistry in all gastric carcinoma tissues. RESULTS: The expression
      of EBV small RNA was positive in 10 out of 155 cases (6.45%). The expression of
      P53 protein was weakly positive in 4 of the 10 cases. The expression level of P53
      protein in EBVaGC was much lower than that in EBVnGC and was weakly positive in
      30 of 145 cases with EBVnGC). P21WAF1 expression was detected in 7 of 10 cases
      with EBVaGC, but in 55 out of 145 cases with EBVaGC, P21WAF1 expression in EBVaGC
      was much higher than that in EBVnGC. CONCLUSION: There seems existing a special
      mechanism of pathogenesis in EBVaGC. In which P53 gene mutation may not play an
      important role.

PMID- 16642207
TI  - [Epidemiological investigation of human papillomavirus infection in men attending
      a sexually transmitted disease clinic in Hangzhou area].
AB  - BACKGROUND: To investigate the epidemiological characteristics of human
      papillomavirus (HPV) infection in men attending a sexually transmitted diseases
      (STD) clinic in Hangzhou area. METHODS: The enrolled individuals were men aged 18
      70 years attending the STD clinic. Penile swabs were assessed for HPV DNA using
      polymerase chain reaction with the consensus primers MY09/11. The HPV genotypes
      of positive PCR products were determined by restriction fragment length
      polymorphisms and direct sequence analysis. RESULTS: Of 375 swabs collected, 305
      (81.3%) yielded sufficient DNA for the subsequent HPV analysis. Among the 305
      subjects, the prevalence of HPV was 13.8%. Low risk HPV types were found in 8.5%
      (26/305) of the enrolled individuals, high risk types were found in 4.3% (13/305)
      of the enrolled individuals, and multiple types were found in 1.0% (3/305) of
      participants. The prevalence of HPV infection was higher in participants from
      urban area than in those from rural area (P<0.05). The prevalence was also higher
      in those who had received less years of education (P<0.05) and those who had more
      sex partners (P<0.05). CONCLUSION: HPV infection among men at high risk is not
      uncommon. The detection rate of HPV DNA was significantly related to some
      sociodemographic factors, such as residence, educational level and the number of
      sex partners.

PMID- 16642208
TI  - [Expression and characterization of transcutaneous immunization adjuvant LTB and
      LTK63].
AB  - BACKGROUND: To study a new kind of adjuvant: transcutaneous immunization
      adjuvant. METHODS: The full length gene of Heat-labile enterotoxin (LT) was
      amplified from E. coli H10407. The B subunit protein LTB and the nontoxic A
      subunit protein LTKA were expressed by genetic engineering manipulation. After
      purification, they were identified with SDS-PAGE, GM1-ELISA and so on. RESULTS:
      The LTB protein still persisted its biologic activity that conjugated
      specifically with GM1 ganglioside, and the LTK63 protein lost its toxin activity.
      CONCLUSION: The results showed that LTB and LTK63 may be used as promising
      transcutaneous immunization adjuvant.

PMID- 16642209
TI  - [Immune complex induced rat liver fibrosis model by intraperitoneal injection of
      human serum albumin].
AB  - BACKGROUND: To establish an immune complex induced rat liver fibrosis model by
      intraperitoneal injection of human serum albumin (HSA). METHODS: Male Wistar
      rats, weighting 110-120 g, were sensitized with HSA by subcutaneous injections at
      different sites for 4 shots at intervals of 14, 10 and 10 days. Ten days after
      the fourth injection, the peritoneal booster dose of HSA was administrated to
      rats twice weekly for 8 weeks with an initial dose of 5 mg, and progressive
      increase to 20 mg. Liver biopsy was performed at the beginning of HSA booster,
      15, 30, 60 days after HSA booster, and 30, 60, 90, 120 days after discontinuation
      of HSA booster, respectively. Liver samples were examined for histological
      changes and liver hydroxyproline (HyP) was measured by biochemical method.
      Fibrosis serum markers hyaluronate acid (HA) and laminin (LN) were determined by
      RIA method. RESULTS: After intraperitoneal administration of HSA, the degree of
      liver pathological changes, the liver Hyp content and serum HA and LN increased
      (P<0.05). The longer the HSA administrated, the higher the liver pathological
      change degree (P<0.05) and the levels of liver Hyp and serum HA (P<0.01). After
      discontinuation of HSA, the levels of serum HA and liver Hyp decreased
      significantly (P<0.01) but were still significantly higher than those in the
      controls (P<0.01). The liver fibrosis formation rate was 100% and the fibrosis
      lasted more than 120 days. CONCLUSION: Intraperitoneal administration of HSA to
      make rat immune complex induced liver fibrosis model is convenient with high
      liver fibrosis formation rate and long fibrosis lasting time. The model may be
      used to evaluate the therapeutic effect of antifibrotic drugs.

PMID- 16642210
TI  - [Variant genotyping of CCR2-64I, SDF1-3' A and CCR5Delta32 in HIV-1 infected
      Chinese long-term nonprogressors].
AB  - BACKGROUND: To investigate variant genotyping of CCR2-64I, SDF1-3'A and
      CCR5Delta32 in HIV-1 infected Chinese Long-term nonprogressors and to study their
      association with disease progression. METHODS: The genotypes of CCR2-64I, SDF1
      3'A and CCR5Delta32 were detected by polymerase chain reaction/restriction
      fragment length polymorphism (PCR/RFLP) assay in seventeen HIV-1 infected Chinese
      Long-term nonprogressors (LTNPs) and thirty-nine Chinese typical progressors
      (TPs). RESULTS: The frequency of CCR2-64I and SDF1-3'A in LTNPs are 50% and
      62.5%, higher than those (23.08% and 33.33%) in TPs. Only one heterozygous CCR5
      mutant was detected in LTNPs, and no CCR5 mutant in TPs. CONCLUSION: Variant
      genotyping of CCR2-64ISDF1-3'A and CCR5Delta32 may be protective factors for
      delaying disease progression in HIV-1 infected Chinese LTNPs.

PMID- 16642211
TI  - [Variability of human cytomegalovirus UL144 gene in low-passage clinical isolates
      analyzed by HMA-SSCP].
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection is an important infectious
      agent that results in neonatal disease and congenital deformity. HCMV infection
      may affect in many organs. The different symptoms and tissue tropism of HCMV
      infection perhaps resulted from the genetic polymorphism of HCMV. HCMV UL144 open
      reading frames encode a homologue of the tumor necrosis factor receptor. It seems
      important to study the strain-specific variability of UL144 sequence in low
      passage clinical isolates and to discuss if the variability related to the
      clinical HCMV infection. METHODS: HCMV-UL144 gene was amplified by PCR assay in
      65 low-passage clinical isolates and urine from 7 healthy children who were HCMV
      DNA positive by quantitative PCR. All the positive PCR products were analyzed by
      Heteroduplex mobility assay and single-stranded conformation polymorphism (HMA
      SSCP) and 32 of them were sequenced. RESULTS: Fifty-five isolates and 5 urine
      specimens were HCMV-UL144 positive by PCR. Sequencing and HMA-SSCP analysis
      showed that significant strain-specific variability was present in the UL144
      ORFs. Comparing UL144 sequences and the corresponding symptoms showed that
      genotype 2 did not exist in megacolon isolates. And genotype 1 and 3 were the
      major types among microcephaly and jaundice isolates respectively. CONCLUSION:
      HCMV-UL144 existed in almost all the low passage isolates. HMA-SSCP assay is an
      easy and effective method to detect the genetype of HCMV-UL144 sequence. The
      characteristic of sequences in different isolates showed that UL144 gene may play
      an important role in HCMV infection.

PMID- 16642212
TI  - [Polymorphisms of HCMV US28 gene of the clinical isolates from children].
AB  - BACKGROUND: To study the polymorphism of human cytomegalovirus US28 gene in
      children and investigate the relationship between the polymorphism and
      pathogenesis. METHODS: The FQ-PCR was carried out to determine the DNA quantity
      of clinical isolate and then the segmental PCR and HMA-SSCP were performed to
      test the mutation of US28 gene. The typical isolates from different diseases were
      selected to clone and sequence, then the results were analyzed. RESULTS: The
      nucleic acid mutation is frequent among the sequence of US28, those mutations
      focus on the two ends of US28, but most of them are sense mutation. The important
      functional groups of US28 are highly conserved. The amino acid mutation of some
      isolates resulted in the change of secondary structure, but the phylogenetic tree
      analysis did not show any clear association between the pathogenesis and the
      distribution of clinical isolates. The comparison of US28 sequences from AIDS
      patients with the sequences from children in our study showed that both sequences
      have their own specific high mutation points. CONCLUSION: There is polymorphism
      among the HCMV-US28 gene of clinical isolates from children. There observed no
      clear relationship was between the pathogenesis and the distribution of clinical
      isolates.

PMID- 16642213
TI  - [Transcriptional inhibitory effect of hepatitis B virus X protein on the
      expression of p53 tumor suppression gene].
AB  - BACKGROUND: To investigate the transcriptional inhibitory role of hepatitis B
      virus X protein on the expression of p53 tumor suppression gene. METHODS: The
      promoter sequence of the p53 tumor suppression gene was identified and amplified
      by bioinformatics and polymerase chain reaction (PCR). The recombinant reporter
      gene expression vector pCAT3-p53p was constructed and transfected into the
      hepatoblastoma cell line HepG2 and cotransfected with pcDNA3.1 (-)-X by Fugene 6
      transfection reagents. The chloramphenicol acetyl transferase (CAT) activity was
      detected by enzyme-linked immunosorbent assay (ELISA). The expression of p53 mRNA
      was further detected by RT-PCR with or without HBV X protein. RESULTS: The
      reporter vector pCAT3-p53p has been successfully constructed and identified and
      the p53 promoter could cis-activate the transcription of the CAT gene. The
      relative expression level of CAT gene in HepG2 cells cotransfected with pCAT3
      p53p and pcDNA3.1 (-)-X was lower than the control, and the inhibitory rate was
      approximately 78%, which indicate that HBV X protein could transcriptionally
      inhibit the activity of p53 promoter. After transfected with pcDNA3.1 (-)-X, the
      expression of p53 mRNA was lower than the control. CONCLUSION: HBV X protein
      could transcriptionally inhibit the expression of p53 tumor suppression gene,
      which might be a possible molecular mechanism responsible for the development of
      HBV-associated hepatocellular carcinoma.

PMID- 16642214
TI  - [Relationship between Shenzhen HBV genotype and precore/core promoter mutation
      and antiviral effects].
AB  - BACKGROUND: To study the relationship between hepatitis B virus genotyping
      Shenzhen isolates and HBV precore/core promoter mutation and antiviral effects.
      METHODS: The HBV genotyping of 165 patients with HBV was carried out with mAbs
      ELISA. HBV precore/core promoter mutation was detected with gene chip technology
      in 24 patients with CHB. The relationship between HBV genotyping and interferon,
      lamivudine effects was analyzed. RESULTS: (1) Out of 165 cases, 106 (64.2%) of
      type B but 48 (29.1%) of type C were found. Type B accounted for 95.4% in group
      ASC, and type C for 64.7%in group LC (P<0.05). (2) Precore/core promoter mutation
      was found in 16 cases (10 of type B, and 6 of type C) out of 24 cases. Out of 16
      cases, precore/core promoter mutation (nt1896, 1862) was found in 10 cases (9
      cases of type B and 1 case of type C), while basal core promoter mutation (BCP
      mutation, nt1762,1764) was found in 6 cases (1 case of type B and 5 of type C).
      (3) Among 27 patients with CHB HBAg (+) treated with interferon, 11 cases of type
      B but 1 case of type C were tested to be fully responsive to interferon. Among 29
      patients with CHB HBAg (+) treated with lamivudine, 15 cases of type B but 3
      cases of type C were tested to be continuously responsive to lamivudine.
      CONCLUSION: (1) HBV genotype popularity in Shenzhen area was classified as type B
      the first and type C the second. (2) Type C seems more apt to develop BCP
      mutation and cirrhosis, and to be less responsive to interferon or lamivudine.

PMID- 16642215
TI  - [Preliminary study on determination of specific cellular immunity of patients
      with hepatitis B].
AB  - BACKGROUND: To evaluate an enzyme linked immunospot (ELISPOT) method for testing
      the specific cellular immunity of patients with hepatitis B and preliminarily
      investigate into the difference of cellular immunity in patients with various
      types of hepatitis B. METHODS: The patients with acute hepatitis B, chronic
      hepatitis B liver cirrhosis, healthy persons with HBV vaccine immunization,
      healthy persons with past HBV infection and HBV naive persons were enrolled in
      this study. Their peripheral blood mononuclear cells were tested by ELISPOT to
      determine the number of gamma-interferon secreting cells. RESULTS: The number of
      gamma-interferon secreting cells was significantly different between the patients
      with acute hepatitis B and those with chronic hepatitis B, and between the
      patients with acute hepatitis B and those with liver cirrhosis (P=0.0209 and
      P=0.0211). CONCLUSION: The specific cellular immunity in the patients with
      hepatitis B could be evaluated by determining the number of gamma-interferon
      secreting cells with the method of testing their peripheral blood mononuclear
      cells by ELISPOT. The specific cellular immunity was stronger in the patients
      with acute hepatitis B than in those with chronic hepatitis B and liver
      cirrhosis.

PMID- 16642216
TI  - [Evaluation of procleix HIV/HCV RNA diagnostic assay].
AB  - BACKGROUND: To investigate the sensitivity and specificity of Procleix HIV/HCV
      RNA diagnostic assay. METHODS: HIV antibody positive or suspected positive
      plasmas of blood donors were collected from different provinces and detected with
      HIV antibody ELISA and HCV antibody ELISA. Samples positive for HIV by ELISA were
      confirmed by using HIV Blot. All the plasma samples were detected with Procleix
      HIV/HCV assay, HIV-1 discriminatory assay and HCV discriminatory assay,
      respectively. RESULTS: All 74 samples positive for both HIV and HCV antibody were
      positive and 5 samples negative for both HIV and HCV antibody were negative when
      detected using Procleix HIV/HCV assay; 82 of 84 supplemental HIV antibody
      positive samples and 6 of 12 supplemental indeterminate samples were positive for
      HIV RNA, and all 7 HIV antibody negative samples were negative for HIV RNA when
      detected by using Procleix HIV discriminatory assay. Seventy of 81 HCV antibody
      positive samples and 4 of 22 HCV antibody negative samples were positive for HCV
      RNA when detected by using Procleix HCV discriminatory assay. CONCLUSION: This
      reagent is more sensitive and could be used in blood screening, thereby can
      reduce both HIV and HCV transmission of blood in window period of HIV and HCV
      infection.

PMID- 16642217
TI  - [Dynamics of in vitro amyloid fiber formation of yeast prion protein Sup35NM].
AB  - BACKGROUND: To investigate the dynamics of amyloid fiber formation of yeast
      (Saccharomyces cerevisiae) prion protein Sup35NM under the native condition to
      provide materials and clues for the elucidation of amyloid fiber formation.
      METHODS: The Sup35NM gene was cloned and expressed in E. coli. The recombinant
      Sup35NM protein was purified under denaturing conditions through Nickel-Sepharose
      chromatography. Aliquots were removed at designated time points for transmission
      electron microscopy (TEM), circular dichroism (CD) spectra, protease K resistance
      assay, as well as thioflavin T (ThT) binding assay. RESULTS: The Sup35NM
      expressed and purified under denaturing conditions. The morphological alteration
      of the Sup35NM in PBS (pH7.4) during the protein aggregation and amyloid fiber
      formation was visualized by TEM. The CD assay showed that the course of amyloid
      fiber formation underwent a conformational shift from alpha-helix to beta-sheet.
      The fibers had higher capacity of resistance to protease K digestion compared to
      the monomers. ThT fluorescence assay displayed a rapid growth phase before
      reaching a final equilibrium phase during the fiber formation, and the higher
      concentration of Sup35NM could greatly accelerate the fiber formation in vitro.
      CONCLUSION: Yeast prion protein Sup35NM forms amyloid readily under native
      conditions in vitro. The dynamics of Sup35NM amyloid formation may provide
      supporting evidences for the nucleating polymerization models of amyloid fiber
      formation.

PMID- 16642218
TI  - [Clinical profiles of circulating dendritic cell phenotype and lymphocyte subsets
      in patients chronically infected with HBV during lamivudine treatment].
AB  - BACKGROUND: To investigate the changes of circulating dendritic cell (DC) and
      lymphocytes subsets in chronic hepatitis B patients treated with lamivudine.
      METHODS: Sixteen chronic hepatitis B patients treated with lamivudine were
      included and followed up for 48 weeks in this study. Before and during lamivudine
      treatment, DC collected from peripheral blood sample was cultured in vitro and
      surface markers of DC and lymphocytes subsets were detected by flow cytometry
      simultaneously. RESULTS: Of the 16 patients, 11 were consistently HBV DNA
      negative in serum and HBV DNA YMDD variants appeared in 5 cases. In the
      consistent responder group, HLA-DR level of DC decreased transiently in 12 weeks
      and recovered in 48 weeks (P<0.05). At 48 weeks CD80, CD40 and CD1a were improved
      compared with baseline level (P<0.05). In the YMDD variant group, CD83 and HLA-DR
      level of DC decreased at 12 weeks treatment (P<0.05) and HLA-DR was still lower
      compared with baseline (P<0.05). In the consistent responder group, no
      significant changes occurred in lymphocyte subsets number at 12 weeks treatment,
      but CD4 + T cell was improved and NK cell dropped at 48 weeks compared with
      baseline level (P<0.05). In the YMDD variant group lymphocyte subsets had no
      statistically significant change. CONCLUSION: In the consistent responder group,
      the expression of surface costimulatory molecules of DC, such as CD80 and
      CD40,was partly recovered after the virus of hepatitis B had been inhibited
      efficiently, HLA-DR levels of DC decreased transiently at 12 weeks and recovered
      in 48 weeks and CD4+ T cell improved and NK cell dropped at 48 weeks. In the YMDD
      variant group, HLA-DR levels of DC were lower consistently during treatment
      compared with baseline level.

PMID- 16642219
TI  - [Detection of Banna virus-specific nucleic acid with TaqMan RT-PCR assay].
AB  - BACKGROUND: To develop a rapid and more sensitive TaqMan RT-PCR assay specific
      for Banna virus. METHODS: Total RNA of strains of Banna virus and other
      arboviruses were extracted and reverse transcribed to cDNAs. With the cDNAs as
      templates, the TaqMan RT-PCR assay was developed and optimized on ABI 7300
      apparatus for specific-detection of Banna virus. The sensitivity, specificity and
      the possibility of this assay to detect Banna virus in pools of mosquitoes.
      Meanwhile, human sera samples added with different dilutions of Banna virus
      culture medium supernatant were evaluated. RESULTS: All the collected 12 Banna
      virus strains in our country were detected as positive, while the results of
      other arboviruses such as Japanese encephalitis virus (JEV), Batai virus, Sindbis
      virus and Orbiviruses were negative. This assay was more than 100 times sensitive
      than that of traditional PCR. About 0.5 CCID-50 of Banna virus in 50 microl
      samples could be detected with this assay. The sensitivity decreased by about 10
      times when the dsRNA was denatured in 65 degrees C instead of 99 degrees C, and
      also when the virus seeds were kept at room temperature for 1 day or 1 week at 4
      degrees C. There was no significant difference in the results of Banna virus
      detection between artificial human serum samples and positive control virus. Six
      were detected as positive for Banna virus-specific nucleic acids in 112 pools of
      mosquitoes, while 3 was positive with virus isolation. CONCLUSION: The Banna
      virus-specific TaqMan RT-PCR assay was proved to be highly sensitive, specific
      and showed a good reproducibility; the assay may be applied for surveillance of
      this virus in clinical samples and pools of mosquitoes screening.

PMID- 16642220
TI  - [Isolation and identification of arboviruses in Hebei Province].
AB  - BACKGROUND: To study the arboviruses carried by mosquitoes collected in Hebei
      Province. METHODS: Samples were collected from mosquito active sites and stored
      in liquid nitrogen till use. Pools of 20 to 30 mosquitoes were ground after
      sterilization, centrifugal supernant was inoculated onto C6/36 cell, cytopathic
      effect was observed for three sequential passages. Positive isolates were
      identified by IFA and RT-PCR. RESULTS: Totally 1310 mosquitoes were collected
      from two villages of She county, Hebei province. They were divided into 46 pools
      and ground respectively. Thirteen positive isolates were obtained. Two isolates
      reacted with alphaviral antibodies and were amplified by alphaviral primers,
      nucleotide sequence showed the highest homology (98%) to Getah virus
      (AY702913.1), so the two isolates were identified as Getah virus. CONCLUSION:
      Getah virus was isolated from mosquitoes in Hebei Province. This is the first
      report of isolating Getah virus from inland of China.

PMID- 16642221
TI  - [Comparison of nucleotide and deduced amino acid sequences of E gene of the newly
      isolated Japanese encephalitis virus strains and inactivated vaccine strain P3].
AB  - BACKGROUND: To analyze the difference of nucleotides and deduced amino acids
      sequences E gene between the newly isolated Japanese encephalitis (JE) virus
      strains from mosquitoes or patients and P3 strain. METHODS: The E gene sequences
      of corresponding strains of JE virus were obtained from GenBank. Computer analyze
      of nucleic acid data and deduced amino acid sequence were accomplished using the
      Clustal X (1.8), DNASTAR, GENEDOC (3.2) programs. RESULTS: The result showed that
      compared with the Fujian strains and P3 strain the nucleotide sequence homology
      was up to 98.3%, and the amino acid sequence homology was up to 98.2%,
      respectively. Compared with the Shanghai strains and P3 strain, the nucleotide
      sequence differences were 12%, and the amino acid sequence homology was up to
      98.2%, respectively. Compared with P3 strain, there were nineteen amino acid
      variations in E gene of all the newly isolated strains. Between P3 and all the
      newly isolated JE virus strains, there are three common variations at E-129, E
      222, E-366. And two common variations E-160 and E-487 were found only in Fujian
      strains, common variations at E-129, E-222, E-227, E-366 in Shanghai strains.
      CONCLUSION: There are some differences between P3 strain and JE viruses which
      were isolated from mosquitoes belonging to genotype I in Shanghai and from
      patients belonging to genotype III from Fujian province. But these variations are
      not in the important locations affecting the biological characteristic of the
      viruses.

PMID- 16642222
TI  - [Isolation and identification of Japanese encephalitis virus in Liaoning
      Province].
AB  - BACKGROUND: To study arboviruses carried by mosquitoes in Liaoning Province in
      2002. METHODS: Totally 4927 mosquitoes were collected from Liaoning Province in
      July 2002. Virus strains were isolated by inoculating BHK-21, C6/36 and Vero
      cells. The newly isolated strains were identified by serological (ELISA and IFA)
      and molecular methods (Real-Time PCR and RT-PCR). RESULTS: Two strains were
      isolated from mosquitoes causing cytopathogenic effect (CPE) on cells and were
      fatal to suckling mice. Serological tests showed that both were positive for the
      antibody to JEV. The PrM and E gene were cloned and sequenced. The phylogenetic
      analysis showed that the new isolates belonged to genotype I, JEV. Sequence
      analysis showed that the homology of nucleotide sequences and amino acid (AA)
      sequences between the two strains was 100%. Compared with the nucleotide
      sequences between the two strains and the standard JEV vaccine strain SA14-14-2,
      the difference was up to 4.11%, and the difference of AA was 0.6%. CONCLUSION:
      Two strains of JEV were isolated and identified in Liaoning province, both
      belonged to genotype I JEV.

PMID- 16642223
TI  - [Etiology of aseptic meningitis prevalent in Xuzhou].
AB  - BACKGROUND: To find the pathogenic agents of aseptic meningitis prevalent in
      Xuzhou of Jiangsu province in 2001. METHODS: The enterovirus (EV) was cultured
      from CSF of the patients and identified with anti-serum by neutralization test.
      Neutralization titer of antibody in paired sera from meningitis children was
      determined. EV RNA was detected by RT-PCR. RESULTS: Four strains of
      Coxsackievirus B5, 2 strains of Coxsackievirus B3 and 1 strain of Echovirus 7
      were isolated from 22 CSF specimens. The isolation rate of virus was 31.8%
      (7/22), 21 CSF were tested by RT-PCR, the positive rate of EV RNA was 52.4%
      (11/21); 57.9% (11/19) of patients paired-sera had over 4 folds antibody rise or
      became seroconverted. CONCLUSION: Enterovirus was the pathogenic agent of aseptic
      meningitis prevalent in Xuzhou of Jiangsu province, the main serotype of the
      virus was Coxsackievirus B5.

PMID- 16642224
TI  - [Clinical evaluation of therapeutic effects of "Cooling the blood and
      invigorating blood circulation" method on hepatitis hyperbilirubinemia].
AB  - BACKGROUND: To explore the effect of treating hepatitis hyperbilirubinemia with
      Chinese traditional "cooling the blood and invigorating blood circulation"
      method. METHODS: Seventy-two patients were randomly divided into two groups. The
      control group (n=36) was treated with hepatocyte growth factor (HGF) 80-120 mg
      daily on the basis of routine western medicine treatment. The therapy group
      (n=36) was treated with "cooling the blood and invigorating blood circulation"
      decoction on the basis of routine western medicine treatment. After using the
      medicine for 28 days, alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), total bilirubin (TBIL), albumin (ALB) in plasma were measured to compare
      the effects of the two methods. RESULTS: The effective rate of the therapy group
      was 80.55%, that of the control group was 50%. There was significant difference
      in efficacy between the two groups (P<0.05). CONCLUSION: "Cooling the blood and
      invigorating blood circulation" method may be effective and safe in the treatment
      of hepatitis hyperbilirubinemia.

PMID- 16642225
TI  - [Significance of blood HCV RNA screening in the prevention of post-transfusion
      hepatitis C].
AB  - BACKGROUND: To investigate the significance of blood HCV RNA screening in the
      prevention of post-transfusion hepatitis C. METHODS: Totally 56,400 anti-HCV
      negative blood samples collected from Jan. 2000 to Dec. 2003 were tested for HCV
      RNA by RT-PCR, and the patients who received the HCV RNA negative blood were
      followed up. RESULTS: The HCV RNA positive rate was 2.5 per thousand (146/56,000)
      and none of the patients followed up suffered from HCV infection. CONCLUSION: HCV
      RNA screening for the anti-HCV negative blood samples is very effective and
      feasible for prevention of post-transfusion hepatitis C.

PMID- 16642226
TI  - Predictors of loss of asthma control induced by corticosteroid withdrawal.
AB  - BACKGROUND: Asthma guidelines recommend reducing the dose of inhaled
      corticosteroids after establishing control. OBJECTIVE: To identify predictors of
      loss of control and the kinetics of symptoms, and inflammatory and physiological
      measurements when inhaled corticosteroids are reduced in patients with stable
      asthma. PATIENTS AND METHODS: In a single-blind study, the daily dose of inhaled
      corticosteroid was reduced by one-half at intervals of 20+/-2 days in 17 adults
      with controlled asthma until loss of asthma control occurred or until the
      corticosteroid was replaced with placebo for 20 days. The patients recorded
      symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s
      (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1
      (PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured
      every 10 days. A loss of asthma control was defined as a worsening of the
      symptoms score of at least 20%, and either a decrease in FEV1 of at least 15% or
      a decrease in PC20 of at least fourfold. RESULTS: Two patients had a respiratory
      infection and were withdrawn from the study. In eight patients, asthma became
      uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately
      reflected by a worsening of all parameters. The first parameter to change was the
      sputum eosinophil percentage (20 days before the loss of asthma control).
      Significant changes in exhaled nitric oxide, FEV1 and methacholine PC20 were
      observed only when the symptoms became uncontrolled. A high blood eosinophil
      count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in
      sputum eosinophil count after the reduction of corticosteroids were predictors of
      loss of asthma control. CONCLUSION: In patients whose asthma is controlled on
      inhaled corticosteroid, it is prudent not to reduce the dose further if the blood
      eosinophils are increased or if the sputum eosinophils increase by as little as
      1% after the reduction of corticosteroids.

PMID- 16642227
TI  - Oral corticosteroid use and the risk of acute myocardial infarction in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Given the limited efficacy of oral corticosteroids in treating
      chronic obstructive pulmonary disease (COPD), the possible cardiac side effects
      of oral corticosteroids are of particular concern in an elderly population. The
      impact of the use of oral corticosteroids on the risk of acute myocardial
      infarction (AMI) in a cohort of patients with COPD was studied. METHODS: The
      Saskatchewan health services databases were used to form a population-based
      cohort of 5648 patients aged 55 years or older who received a first treatment for
      COPD between 1990 and 1997. A nested case-control analysis was conducted: 371
      cases presenting with a first myocardial infarction were matched with 1864
      controls according to the length of follow-up, the date of cohort entry and age.
      Conditional logistic regression was used to adjust for sex, severity of COPD,
      systemic hypertension, diabetes and prior cardiovascular disease. RESULTS: Only
      the current use of corticosteroids was associated with an increased risk of AMI
      (adjusted RR=2.01 [95% CI 1.13 to 3.58]), particularly when the current dose was
      larger than 25 mg/day of prednisone or the equivalent (adjusted RR=3.22 [95% CI
      1.42 to 7.34]). This observed increase in risk rapidly returned to baseline after
      the cessation of the medication, suggesting that the use of such high doses
      reflected the treatment of acute exacerbations of the disease. CONCLUSIONS: An
      association was found between the current use of oral corticosteroids and the
      occurrence of an AMI, suggesting that acute exacerbations of COPD are associated
      with an increased risk of acute coronary syndromes.

PMID- 16642228
TI  - Reasons for coming to hospital after treatment for community-acquired pneumonia
      on an ambulatory basis.
AB  - BACKGROUND: Most patients with community-acquired pneumonia (CAP) are treated on
      an ambulatory basis. OBJECTIVE: To evaluate the reasons for presentation to
      hospital after treatment for CAP on an ambulatory basis. METHODS: The study,
      conducted in five hospitals in the Capital Health Region (Edmonton, Alberta),
      enrolled adult patients aged 17 years or older who presented with a history of
      having been diagnosed and treated for pneumonia within the previous month. A
      current diagnosis of pneumonia was based on two or more symptoms or signs of CAP,
      plus radiographic evidence of pneumonia. RESULTS: Seventy-five (77.3%) of the 97
      patients who met the inclusion criteria had CAP, and 22 (22.7%) patients
      presented with a noninfectious illness. Of the patients with CAP, 25 (33.3%) met
      the study criteria for worsening of a comorbid illness, 23 (30.7%) had clinical
      failure, 16 (21.3%) had microbiological failure, six (8.0%) were noncompliant,
      four (5.3%) had failure of expectations and one (1.3%) had adverse effects of
      antimicrobial therapy. CONCLUSIONS: Underlying diseases, exacerbations of
      comorbidities and complications of CAP, as well as confounders such as unusual
      infections and noninfectious conditions that mimic CAP, are all reasons for
      presenting to hospital after treatment for CAP in an ambulatory setting.

PMID- 16642229
TI  - Preservation of pleural integrity during coronary artery bypass surgery affects
      respiratory functions and postoperative pain: a prospective study.
AB  - OBJECTIVE: To evaluate the role of preserved pleural integrity in postoperative
      pain and respiratory functional status in patients undergoing coronary
      revascularization. METHODS: Two hundred forty patients undergoing on-pump
      coronary artery bypass grafting between March 2004 and February 2005 were
      included in the present study. The patients were prospectively randomized and
      divided into either an opened pleura (OP) group (n=120, patients with an OP) or a
      closed pleura (CP) group (n=120, patients whose pleural integrity was preserved).
      Preoperative patient characteristics were similar. Postoperative respiratory
      functions were compared between the groups by chest x-rays, respiratory
      functional tests and arterial blood gas analyses. Postoperative pain was compared
      by using a multidimensional pain score. All the tests were examined by the same
      blinded clinician. RESULTS: The mean age of the patients was 60.4+/-8.8 years.
      Postoperative bleeding and the duration of hospital stay were markedly higher in
      the OP group than in the CP group. The incidences of atelectasis and pleural
      effusion were also significantly higher in the OP group (P<0.01). Respiratory
      functions and postoperative pain scores were better in the CP group (P<0.01 and
      P=0.008, respectively). CONCLUSIONS: Preserving pleural integrity has beneficial
      effects on the respiratory functions and postoperative pain after coronary
      revascularization. The preservation of pleural integrity results in better
      respiratory function, decreased hospital stay and cost, and as a consequence, a
      better surgical outcome.

PMID- 16642230
TI  - Pneumonitis after inhalation of mercury vapours.
AB  - A 43-year-old man presented to hospital with pneumonia but only after discharge
      from hospital did he admit to deliberate prior inhalation of mercury. His
      pulmonary involvement appeared to resolve almost completely with antibiotics and
      supportive care. Nevertheless, persisting elevated urinary excretion of mercury
      required two courses of chelation therapy. No serious systemic sequelae were
      observed.

PMID- 16642231
TI  - GI malignancies in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of consultations involving the management of
      gastrointestinal (GI) malignancy. In this analysis we have included all bowel
      cancers; upper GI malignancies (stomach, oesophagus); and 'other' which include
      carcinomas of the liver, gall bladder, pancreas, tongue and parotid gland. This
      synopsis provides a backdrop against which the theme articles in this issue of
      Australian Family Physician can be further considered.

PMID- 16642232
TI  - Bowel cancer screening in Australia.
AB  - BACKGROUND: Modern screening tools have the potential to decrease mortality and
      morbidity from bowel cancer, the second commonest cause of cancer death. The
      evaluation of the recent National Bowel Cancer Screening Pilot Program (NBCSPP)
      in Australia has prompted the commonwealth government to fund the first phase of
      the National Bowel Cancer Screening Program in May 2006. OBJECTIVE: This article
      discusses the evidence for bowel cancer screening and the outcomes of the NBCSPP.
      DISCUSSION: Inexpensive tests are available to detect bleeding from the large
      bowel, a stronger indicator of early bowel cancer than symptoms, and pilot
      projects confirm their feasibility and acceptability in Australia. A doctor's
      recommendation strongly influences individual participation in screening. The
      medical profession are more likely to support an organised screening program if
      they are informed on the evidence on which the screening program is based.

PMID- 16642233
TI  - Bowel cancer - guide for the GP.
AB  - BACKGROUND: Many patients will remain asymptomatic until the advanced stages of
      colorectal cancer and hence, will only be identified by means of a coordinated
      screening program. OBJECTIVE: This article outlines the risk assessment, early
      detection primary prevention and management of colorectal cancer. DISCUSSION: It
      is vital that general practitioners recognise the enormous variation in the
      patterns of clinical presentation of colorectal neoplasia such as rectal
      bleeding, iron deficiency anaemia, change in bowel habit, and unexplained weight
      loss. Any patient over 40 years of age presenting with rectal bleeding should be
      considered for colonoscopy. In patients in whom a colorectal neoplasm has been
      diagnosed, preoperative workup and counselling is of paramount importance.
      Primary treatment of colorectal cancer is surgical resection and often adjuvant
      chemotherapy. Patients with rectal tumours have a greater risk of complications
      of surgery and local recurrence than those with colonic tumours. Patients with
      node positive cancer remain at significant risk for recurrence, despite optimal
      surgery and removal of the primary tumour. Adding oxaliplatin to standard (5FU
      based) chemotherapy has improved disease free survival for high risk patients.

PMID- 16642234
TI  - Diagnosis of upper gastrointestinal malignancy.
AB  - BACKGROUND: Dyspepsia is a common complaint in clinical practice. In the majority
      of cases this symptom will result from gastrooesophageal reflux or peptic
      inflammation or ulceration; however, upper gastrointestinal malignancy may
      present in a similar way. OBJECTIVE: The article aims to assist the general
      practitioner in determining which patients presenting with dyspepsia warrant
      further investigation. DISCUSSION: Patients over the age of 40 years with recent,
      new symptoms and those with dysphagia, weight loss, early satiety, iron
      deficiency anaemia, or more obvious signs such as a palpable epigastric mass or
      liver enlargement, require investigation in the first instance with endoscopy. In
      patients without these 'alarm features' it is reasonable to treat acid reflux
      symptoms with appropriate proton pump inhibitor therapy and only investigate in
      the event of inadequate symptomatic response. Those with symptoms suggestive of
      gastritis or duodenitis can be noninvasively tested for Helicobacter pylori
      infection and re-assessed after successful eradication has been confirmed.

PMID- 16642235
TI  - Management of oesophageal carcinoma.
AB  - BACKGROUND: Treatments for oesophageal cancers have historically been surgical,
      and surgical treatment remains the mainstay of treatment for localised
      oesophageal carcinoma (stage I-III). For stage IV disease, systemic chemotherapy
      is the mainstay of treatment. OBJECTIVE: This article provides an overview of
      curative and palliative management options for oesophageal carcinoma. Surgery,
      endoscopic treatments, and chemotherapy, radiotherapy and combined modality
      chemoradiation are considered. DISCUSSION: Several surgical approaches are
      available and each has its positive and negative aspects. Recent advances in
      chemotherapy and radiotherapy have aided the surgeon's work either by down
      staging tumours and rendering inoperable cases amenable to surgery. These
      adjuvant treatments also benefit the patient by reducing the risk of mediastinal
      and distant metastases.

PMID- 16642236
TI  - Management of gastric cancer.
AB  - BACKGROUND: Gastric cancer is a common disease with a high mortality. OBJECTIVE:
      This article aims to outline the management options for patients with gastric
      cancer. DISCUSSION: The mainstay of curative treatment remains surgical
      resection. The management of early stage gastric cancer is complex with proven
      benefit of both pre-operative chemotherapy and postoperative chemo-radiotherapy,
      as well as complex surgical issues and the patient benefits from management by a
      multidisciplinary team. The most commonly performed operations for gastric cancer
      are total and subtotal gastrectomy, depending on the location of the tumour and
      the ability to gain adequate tumour free margins. Common postoperative
      difficulties include early satiety, postprandial pain and diarrhoea,
      hypoglycaemic episodes and bile reflux. Adjuvant chemotherapy and radiotherapy
      has been demonstrated to have a beneficial role in survival. Palliative surgical
      options are directed at control of symptoms related to bleeding and obstruction.
      Palliative chemotherapy has been shown to confer a survival benefit, however,
      with notable toxicity.

PMID- 16642237
TI  - Pancreatic cancer - current management.
AB  - BACKGROUND: Pancreatic cancer remains a common and lethal cancer with a median
      survival of approximately 6 months. OBJECTIVE: This article discusses the current
      management of pancreatic cancer, both potentially curative and palliative
      treatment. DISCUSSION: Surgical resection of the primary tumour is only possible
      in about 10% of cases as many patients have locally advanced or metastatic
      disease at the time of presentation. For the majority of patients, treatment is
      palliative and may include surgical treatments or endoscopic or percutaneous
      stenting to relieve obstructive jaundice or gastric obstruction, chemotherapy,
      radiotherapy or interventional radiological techniques. Adequate pain relief and
      treatment of pancreatic insufficiency are important components of treatment.

PMID- 16642238
TI  - Life after breast cancer.
AB  - This thirteenth article in our series on breast disease explores the many
      concerns that patients face after completion of their breast cancer treatment.
      The diagnosis and treatment of breast cancer is an ordeal for women on a number
      of levels. Similarly, there are often a multitude of issues and concerns raised
      after the completion of treatment. Having an awareness of these medical and
      survivorship issues allows the general practitioner to provide important support
      to both the patient and her family.

PMID- 16642239
TI  - Until the chemist opens - palliation from the doctor's bag.
AB  - BACKGROUND: People with a life limiting illness may have unpredictable
      exacerbations of their symptoms requiring after hours care by general
      practitioners using medications that are readily accessible. All doctors are
      provided with injectable 'doctor's bag' emergency drugs for use in such a crisis.
      OBJECTIVE: This article aims to: identify which medications from the doctor's bag
      can be used in the palliative care crises that are most frequently encountered,
      present the best possible evidence for these indications, and to provide GPs
      caring for palliative care patients after hours with management strategies so,
      whenever appropriate, they can continue to be managed at home. DISCUSSION: The
      clinical context, including disease trajectory and patient and caregivers'
      wishes, must be assessed in palliative care crises. Having excluded reversible
      problems, symptoms can be treated using doctor's bag medications. Attention must
      be given to route of administration, duration of effect, and appropriate doses
      for effective palliation.

PMID- 16642240
TI  - Remove the tooth, but don't stop the warfarin.
AB  - BACKGROUND: Dentists rely on general practitioners to manage a patient's warfarin
      dose before uncomplicated dental extraction. OBJECTIVE: This article compares
      common practice of warfarin management with the available clinical evidence.
      DISCUSSION: Common practice lags more than 20 years behind clinical evidence to
      the detriment of patients, and with medicolegal consequences for doctors.

PMID- 16642241
TI  - Urinary incontinence in dementia - a practical approach.
AB  - BACKGROUND: Urinary incontinence is a common problem in dementia. Almost
      invariably, the person with dementia will develop incontinence as the disease
      progresses. However, the primary reasons for incontinence are often not because
      of any significant pathology in the urinary system. Rather, it is due to factors
      outside the urinary system. The term 'functional incontinence' has hence been
      applied. Maintenance of continence requires mobility, manual dexterity, mental
      capacit and motivation. Clearly, the person with dementia is vulnerable to
      developing problems in these domains. OBJECTIVE: This article provides a
      comprehensive overview of how the stage and type of dementia may account for
      cognitive and functional deficits, the psycho-emotional world and behaviour of
      the patient, their care environment, and possible medical factors and pathology
      in the urinary system. DISCUSSION: Management is directed at turning around
      reversible factors, preserving independence and dignity of the patient, and
      providing sensitive and empathetic care even if the problem is not completely
      remediable. In those with more advanced dementia, timed and prompted voiding have
      shown the most promise.

PMID- 16642242
TI  - Lifestyle factors in the management of cancer.

PMID- 16642243
TI  - Osteoporosis from androgen deprivation therapy in prostate cancer treatment.
AB  - BACKGROUND: Bone complications from metastatic disease in prostate cancer have
      been well documented. Osteoporosis from androgen deprivation therapy (ADT) can
      further impair quality of life in this already susceptible age group. OBJECTIVE:
      We aimed to assess the intermediate and long term effects of ADT on bone density
      and the development of osteoporosis in men with prostatic cancer, and outline
      some practical assessment, management and treatment options. DISCUSSION:
      Osteoporosis, exacerbated by the use of ADT, reduces both the survival and
      quality of life of men who may otherwise live for many years with their well
      controlled prostate cancer. Hence, both preventive and treatment options should
      be explored and tailored to the individual, including lifestyle modifications
      (exercise, smoking cessation), vitamin D and calcium supplementation, and the use
      of bisphosphonates.

PMID- 16642244
TI  - The duty to follow up.
AB  - Case histories are based on actual medical negligence claims, however certain
      facts have been omitted or changed by the author to ensure the anonymity of the
      parties involved. Many general practitioners are concerned that the law places
      all of the responsibility for follow up on to the GP and ask: 'What is the
      patient's responsibility'? This article explores the duty of GPs and patients to
      follow up tests and results.

PMID- 16642245
TI  - Expressions of interest - writing for success.
AB  - Primary health care research is a growing discipline and as such needs more funds
      to support the increase in this research. With the competition for research funds
      increasing, primary health care researchers need to be astute in how they apply
      for funds. This article provides key points to keep in mind when writing an
      expression of interest to increase your chance of success.

PMID- 16642246
TI  - What are the essential medications in pallative care? - a survey of Australian
      palliative care doctors.
AB  - BACKGROUND: There is a disparity of availability and cost of drugs in the
      community for palliative care patients through the Pharmaceutical Benefits Scheme
      (PBS) compared to those available to inpatients in public hospitals. METHODS: The
      Joint Therapeutics Committee of the Australian and New Zealand Society of
      Palliative Medicine, Palliative Care Australia and the Clinical Oncological
      Society of Australia surveyed palliative care practitioners in Australia to
      compile a list of drugs they considered essential. RESULTS: Drugs nominated
      generally had good levels of evidence for use in palliative care, although many
      practitioners still used some without evidence of benefit. DISCUSSION: We are now
      working with the Commonwealth Department of Health and Ageing to agree on a list
      of drugs for specific palliative care indications. As a result, the first ever
      section in the PBS for a specific patient population has been created. There is a
      need for high quality studies in palliative care to determine the best drugs to
      add to the list.

PMID- 16642247
TI  - Home medicines reviews - do they change prescribing and patient/pharmacist
      acceptance?

PMID- 16642248
TI  - Increasing EBM learning in training GPs - a qualitative study of supervisors.

PMID- 16642249
TI  - Women's decision making at menopause - a focus group study.
AB  - BACKGROUND: Women are faced with a confusion of information and uncertainty when
      making decisions at menopause. METHODS: We conducted four focus groups of 31
      women aged 40-64 years, exploring their experience and views about menopause, its
      management, and decision support needs. RESULTS: Focus group participants saw
      menopause as a natural progression rather than a medical condition, and decision
      making about therapies as a personal responsibility. They wanted reliable, agenda
      free information, and opportunities to discuss personal needs with (preferably
      female) health professionals. They preferred minimal intervention and found life
      style strategies helpful. DISCUSSION: Women's preference to make their own
      decisions at menopause is frustrated by conflicting information and the perceived
      marketing agenda of information sources. Women need unbiased, timely, menopause
      information backed by expert commentary in a range of media to suit their access
      needs.

PMID- 16642250
TI  - Concepts in a multiprong approach to photoaging.
AB  - Photoaging is a multisystem degenerative process that involves the skin and the
      skin support systems, including the bone, cartilage, and subcutaneous
      compartments. These structures provide the architectural support for the dermis,
      epidermis, and stratum corneum. A multiprong approach to photoaging involves
      reversing the undesirable changes in each of these structures. Dermatologists
      should become adept at treating all of the visible manifestations of photoaging.

PMID- 16642251
TI  - Advances in techniques for endovenous ablation of truncal veins.
AB  - The latest techniques for endovenous occlusion, i.e., radiofrequency ablation
      catheters or endoluminal laser targeting water are our preferred methods for the
      treatment of saphenous-related varicose veins. Clinical experience with
      endovenous techniques in more than 1,000 patients shows a high degree of success
      with minimal side effects, most of which can be prevented or minimized with use
      of tumescent anesthesia. Within the next 5 years, these minimally invasive
      endovenous ablative procedures involving saphenous trunks should have virtually
      replaced open surgical strippings.

PMID- 16642252
TI  - Treating autoimmune diseases through restoration of antigen-specific immune
      tolerance.
AB  - The first line of treatment for many human autoimmune diseases involves the use
      of anti-inflammatory or immunosuppressive drugs such as prednisone or other
      steroids that not only suppress the underlying autoimmune disease, but lead to
      global suppression of the immune system. The sequelae of this approach include
      increased risk of infection, carcinogenesis, and osteoporosis. Moreover, such
      broad spectrum immunosuppression tends to have transient therapeutic benefit, as
      in many cases the disease becomes refractory to these drugs. There is a clear
      need for more specific means to restore immune tolerance to the specific
      autoantigens implicated in disease pathology. This review provides an overview of
      some of these newer, more specific therapeutic approaches to restoring immune
      tolerance to autoantigens, with an emphasis on those approaches that have been or
      will soon be tested in controlled clinical trials. Covered here are peptide- or
      protein-based therapeutics, oral tolerance, and cellular and gene therapy
      approaches to restoring antigen-specific immune tolerance.

PMID- 16642253
TI  - Regulation of innate and adaptive immune responses by the related cytokines IL
      12, IL-23, and IL-27.
AB  - The functional characterization and subsequent purification of T cell growth
      factor/interleukin (IL)-2 in the early 1980s established this secreted protein as
      a key mediator of immune cell activation and provided the prototype that enabled
      the discovery of numerous cytokines over the ensuing two decades. While soluble
      immunoregulatory factors were initially identified functionally as biological
      activities present in the culture supernatants of activated
      lymphocytes/monocytes, this methodology shifted radically following the
      completion of the human genome sequence. Computer-generated structural modeling
      algorithms have replaced functional assays and biochemical purification as the
      initial means of discovering new cytokines. To date, a total of 31 interleukins,
      as well as over a dozen other related hematopoietic factors, have been
      identified. These cytokines and their receptors may be grouped on the basis of
      structural homologies as well as by shared ligand and receptor subunits. The
      challenge now at hand is to define the biological functions of the newly
      identified cytokines and to elucidate the common and divergent roles of related
      family members. This point is well illustrated by the IL-12/IL-23/IL-27 family,
      whose members share ligand and receptor subunits and play somewhat overlapping
      roles in innate and adaptive immune responses. These three cytokines are not
      entirely redundant, as they may preferentially activate naive or memory T cells,
      induce discrete T cell cytokine profiles, contribute to distinct stages of host
      immune responses to infectious agents, and differentially promote autoimmunity.
      Further elucidation of the unique functions of the IL-12 family members may lead
      to improved immunodiagnostics and therapies.

PMID- 16642254
TI  - Activation of Salmonella-specific immune responses in the intestinal mucosa.
AB  - The mammalian immune response to Salmonella has long been a subject of scientific
      study. Indeed, many of the general aspects of bacterial pathogenesis and host
      immune defense have been well described. However, a lack of clarity remains
      concerning important aspects of the host immune response to Salmonella,
      particularly with regard to the induction of an immune response in the intestinal
      mucosa. A major limitation has been the general lack of knowledge about specific
      antigenic targets that are recognized by both the innate and adaptive immune
      response in the intestine. Progress towards the identification of these targets
      is critical for the development of a detailed model of immunity to Salmonella and
      will lead to a better understanding of mucosal immune responses to other
      intracellular pathogens.

PMID- 16642255
TI  - Regulatory T cells: magic bullets for immunotherapy?
AB  - In the past few years it has been become increasingly clear that T cells capable
      of actively suppressing immune responses are thought to be in part responsible
      for the maintenance of peripheral self tolerance. In healthy rodents and humans,
      CD4(+) T cells constitutively expressing the interleukin (IL)-2 receptor alpha
      chain (CD25) are able to exert such suppressive function in vitro and in vivo.
      Despite great efforts in our understanding of the biology of such
      immunoregulatory T cells, there are still certain points incompletely understood.
      Although some authors suggest that immunoregulatory cytokines such as IL-10 or
      transforming growth factor-beta are critical for the suppressive effect of these
      cells, this is controversial and the exact molecular nature and the targets of
      suppression are largely unknown. Thus far, until regulatory T cells can be used
      for diagnostic or therapeutic purposes many questions have to be answered. In
      this review we summarize the current knowledge on the function and properties of
      this T cell subset and discuss their potential role in human autoimmune or
      chronic inflammatory diseases.

PMID- 16642256
TI  - Stem cells in nephrology: present status and future.
AB  - Stem cell biology is currently developing rapidly because of the potential
      therapeutic utility of stem cells. The ability to acquire any desired phenotype
      raises hope for regenerative therapies. Manipulation of these cells is a
      potentially valuable tool; however, the mechanisms of stem cell differentiation
      and plasticity are currently beyond our control. In the field of nephrology, the
      presence of adult kidney stem cells has been debated. Renal adult stem cells may
      be descendants of some early kidney progenitors, or may be derived from bone
      marrow. Evidence of a hematopoietic stem-cell contribution to renal repair
      encourages the possibility of bone marrow or stem cell transplantation as a means
      of treating autoimmune glomerulopathies. The transplantation of fetal kidney
      tissue containing renal progenitors, which then develop into functional nephrons,
      is a step towards renal regeneration. According to recent reports, the
      development of functional nephrons from human mesenchymal stem cells in rodent
      whole-embryo culture is possible. Establishing in vitro self organs from
      autologous stem cells would be a promising therapeutic solution in light of the
      shortage of allogenic organs and the unresolved problem of chronic allograft
      rejection.

PMID- 16642257
TI  - Therapeutic effects of cisplatin on rat experimental autoimmune
      encephalomyelitis.
AB  - INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is a prototypic Th1
      mediated autoimmune inflammatory disease of the central nervous system (CNS), and
      serves as a model for the human demyelinating disease, multiple sclerosis.
      Cisplatin is a drug widely used in the treatment of a variety of human
      neoplasias, such as advanced bladder carcinoma, adrenal cortex carcinoma, breast
      cancer, head and neck or lung carcinoma. Cisplatin binds to DNA and interferes
      with cellular repair and other mechanism, which eventually result into cell
      death. It is known that cisplatin can induce immunosuppressive effects through
      inhibition of T cell activity. Therefore we analyzed the anti-inflammatory
      effects of cisplatin in a rat EAE model. MATERIALS AND METHODS: EAE was induced
      in male LEW rats by immunizing with a synthetic peptide of guinea pig myelin
      basic protein. The development of EAE and neurological signs were evaluated by a
      standard protocol. Immunohistochemistry was applied to show immune cell
      infiltration into the CNS. RESULTS: Early treatment of EAE rats with cisplatin
      effectively ameliorated the development of disease and provided a significant
      protective effect compared to control rats. Further, histological analysis
      demonstrated that the formation of the typical perivascular cuffs and brain
      infiltration of monocytes and lymphocytes were complete absent in cisplatin
      treated rats, while abundant T cell infiltration was seen in the CNS of EAE rats.
      CONCLUSIONS: Our data show that cisplatin has protective effects in EAE,
      indicating that cisplatin could be a candidate in the treatment of human CNS
      autoimmunity.

PMID- 16642258
TI  - Routine clinical laboratory tests correspond to increased serum levels of 3
      hydroxy fatty acids, markers of endotoxins, in cardiosurgery patients.
AB  - INTRODUCTION: Endotoxemia developing during cardiosurgery as elevated endotoxin
      concentrations in patient's serum may prevail over 24 h after operation. A major
      reason is thought to be increased gut permeability resulting in endotoxin and
      bacterial leakage. In this study we aimed to measure endotoxin levels on samples
      obtained during and after cardiovascular procedures and compare them with
      clinical observations and laboratory test results. MATERIALS AND METHODS: 3
      Hydroxy fatty acids (3-OH FAs) of 10-18 carbon chain length, chemical markers of
      endotoxin (lipopolysaccharide), were determined in patient sera by gas
      chromatography-mass spectrometry-based analysis. RESULTS were compared with
      routine laboratory tests: blood morphology, urine, ALT, AST, bilirubin, kidney
      parameters, clotting parameters, and gasometry. RESULTS: Of a total of 16
      patients, 5 patients (group I) showed increased serum 3-OH FA levels and 11
      patients (group II) did not show any change in 3-OH FA levels 24 h after
      operation. All group I patients revealed leukocytosis, two developed post
      operative anemia. Significantly different changes were observed: the initial, pre
      operative 3-OH FA levels were similar for both groups, while group I patients
      showed increased levels of all the studied 3-OH FAs during the operation
      (p</=0.05), and 3-OH C14 and 3-OH C16 remained elevated 24 h after the operation.
      CONCLUSIONS: Cardiosurgery may strongly promote gut endotoxin translocation to
      the blood in some patients. Prolonged leukocytosis, deep anemia, and increased
      liver dysfunction markers may indicate the need for observation of possible
      endotoxemia development. It is recommended to monitor the endotoxin level and/or
      endotoxemia markers in cardiosurgery patients.

PMID- 16642259
TI  - Susceptibility of Propionibacterium acnes and Staphylococcus epidermidis to
      killing by MPO-halide system products. Implication for taurine bromamine as a new
      candidate for topical therapy in treating acne vulgaris.
AB  - INTRODUCTION: Taurine chloramine (TauCl) and taurine bromamine (TauBr) are the
      main haloamines produced by activated neutrophils. TauCl exerts both anti
      inflammatory and microbicidal activities. Clinical studies showed that TauCl may
      be useful as an antimicrobial agent in the local treatment of infections. Much
      less is known about TauBr. Circumstantial evidence suggests that
      Propionibacterium acnes (PA) has a role in the inflammation of acne. Available
      topical therapies include antimicrobial agents which reduce total PA numbers and
      anti-inflammatory agents which suppress activity of the cells present in acne
      inflammatory lesions. In this study the bactericidal activities of TauBr and
      TauCl against PA and Staphylococcus epidermidis (SE), as a control strain, were
      investigated. Moreover, the influence of these haloamines on the generation of
      reactive oxygen species (ROS) by activated neutrophils was also tested. MATERIALS
      AND METHODS: TauBr and TauCl were prepared by reaction of taurine with HOBr and
      HOCl, respectively. The reaction was monitored by UV absorption spectra. The
      bactericidal activities of TauBr and TauCl were determined by the pourplate
      method. The generation of ROS by neutrophils was determined by luminol
      chemiluminescence assay. RESULTS: In our experimental set-up, TauBr showed
      stronger antibacterial activity than TauCl. Interestingly, PA was significantly
      more susceptible to TauBr than SE was. Moreover, TauBr at non-cytotoxic
      concentrations significantly reduced ROS generation by neutrophils. CONCLUSIONS:
      Since PA is considered to be an etiological agent in acne and ROS are closely
      correlated with the pathogenesis of inflammatory skin diseases, the reported data
      suggest that TauBr may be a good candidate for the topical therapy for acne
      vulgaris.

PMID- 16642260
TI  - The effect of Chlamydia trachomatis infection of the prostate gland on the
      concentration of citric acid.
AB  - INTRODUCTION: The objective of the study was to assess the relationship between
      Chlamydia trachomatis (C.t.) infection of the prostate and the concentration of
      citric acid. MATERIALS AND METHODS: The study involved 60 patients with chronic
      prostatitis (NIH III). Urethral swabs and expressed prostatic secretions (EPS)
      were collected for analysis. The urethral swabs were tested for PMNs and the
      presence of Neisseria gonorrhoeae and C.t., while the EPS were analyzed to
      determine PMN count, C.t., and citric acid concentration. The DFA or LCR method
      was used for C.t. diagnosis. The concentration of citric acid was measured using
      the UV method. RESULTS: Inflammation of the prostate (PMNs >/=10/field) was
      diagnosed in 58.3 of the patients. C.t. infection was found in 20%, including
      8.3% with only the urethra affected and 10% with only the prostate. One patient
      had both the urethra and the prostate infected. A reduction in the concentration
      of citric acid in EPS was observed in 56.7% of the men. In 88.2% of the patients,
      reduced citric acid concentration was accompanied by an elevated PMN count in the
      EPS. All patients with C.t. infection of the prostate showed a reduced
      concentration of citric acid. In five patients with urethral infection, lack of a
      decrease in this parameter was noted in one. In all the patients with chlamydial
      infection, irrespective of localization, a high PMN count was observed in the
      EPS. CONCLUSIONS: Determination of the concentration of citric acid in the
      prostatic fluid is a good indicator of prostatitis. C.t. infection of the
      prostate gland is accompanied by a decrease in the concentration of citric acid.

PMID- 16642262
TI  - Molecular phylogenetic and chemical analyses of the microbial mats in deep-sea
      cold seep sediments at the northeastern Japan Sea.
AB  - Microbial communities inhabiting deep-sea cold seep sediments at the northeastern
      Japan Sea were characterized by molecular phylogenetic and chemical analyses.
      White patchy microbial mats were observed along the fault offshore the Hokkaido
      Island and sediment samples were collected from two stations at the southern foot
      of the Shiribeshi seamount (M1 site at a depth of 2,961 m on the active fault)
      and off the Motta Cape site (M2 site at a depth of 3,064 m off the active fault).
      The phylogenetic and terminal-restriction fragment polymorphism analyses of PCR
      amplified 16S rRNA genes revealed that microbial community structures were
      different between two sampling stations. The members of ANME-2 archaea and
      diverse bacterial components including sulfate reducers within
      Deltaproteobacteria were detected from M1 site, indicating the occurrence of
      biologically mediated anaerobic oxidation of methane, while microbial community
      at M2 site was predominantly composed of members of Marine Crenarchaeota group I,
      sulfate reducers of Deltaproteobacteria, and sulfur oxidizers of
      Epsilonproteobacteria. Chemical analyses of seawater above microbial mats
      suggested that concentrations of sulfate and methane at M1 site were largely
      decreased relative to those at M2 site and carbon isotopic composition of methane
      at M1 site shifted heavier ((13)C-enriched), the results of which are consistent
      with molecular analyses. These results suggest that the mat microbial communities
      in deep-sea cold seep sediments at the northeastern Japan Sea are significantly
      responsible for sulfur and carbon circulations and the geological activity
      associated with plate movements serves unique microbial habitats in deep-sea
      environments.

PMID- 16642263
TI  - A comparative study on the antimutagenicity of atorvastatin and lovastatin
      against directly acting mutagens.
AB  - Elevated levels of oxidative DNA lesions have been noted in many tumors and such
      damage is strongly implicated in the etiology of cancer. The cumulative risk of
      cancer increases with the fourth power of age and is associated with an
      accumulation of oxidative DNA damage. Many agents, synthetic or natural, that can
      inhibit mutation have been depicted as cancer chemopreventive agents.
      Antimutagenicity of the 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase
      inhibitors atorvastatin and lovastatin was studied using the Ames Salmonella
      typhimurium assay. Directly acting mutagens, sodium azide (NaN(3)) and 4-nitro-o
      phenylenediamine (NPDA), were used to induce mutation in Salmonella strains TA98
      and TA100. The antimutagenicity of lovastatin and atorvastatin was found to be
      significant (p < 0.01) and dose-dependent. The percentage inhibition of a 3 mg
      lovastatin-treated plate was found to be 79.9% and 61.8% against NPDA- and NaN(3)
      induced mutation to TA98 and TA100, respectively. Atorvastatin (0.5 mg/plate)
      inhibited NPDA-and NaN(3)-induced mutation to TA98 and TA100 by 78.6% and 45.5%,
      respectively. Atorvastatin showed antimutagenic activity at lower concentrations
      than lovatstatin. The results of the present study regarding the antimutagenic
      activity of atorvastatin and lovastatin suggested their therapeutic application
      as cancer chemopreventive agents.

PMID- 16642264
TI  - PU.1 phosphorylation correlates with hydroquinone-induced alterations in myeloid
      differentiation and cytokine-dependent clonogenic response in human CD34(+)
      hematopoietic progenitor cells.
AB  - The transcriptional regulatory factor PU.1 is important for the regulation of a
      diverse group of hematopoietic and myeloid genes. Posttranslational
      phosphorylation of PU.1 has been demonstrated in the regulation of a variety of
      promoters in normal cells. In leukemia cells, differing patterns of PU.1
      phosphorylation have been described among acute myelogenous leukemia (AML)
      subtypes. Therefore, we hypothesized that modulation of PU.1-dependent gene
      expression might be a molecular mediator of alterations in myeloid cell growth
      and differentiation that have been demonstrated to be early events in benzene
      induced leukemogenesis. We found that freshly isolated human CD34(+)
      hematopoietic progenitor cells (HPC) exhibit multiple PU.1-DNA binding species
      that represent PU.1 proteins in varying degrees of phosphorylation states as
      determined by phosphatase treatment in combination with electrophoretic mobility
      shift assay (EMSA). Maturation of granulocyte and monocyte lineages is also
      accompanied by distinct changes in PU.1-DNA binding patterns. Experiments reveal
      that increasing doses of the benzene metabolite, hydroquinone (HQ) induce a time
      and dose-dependent alteration in the pattern of PU.1-DNA binding in cultured
      human CD34(+) cells, corresponding to hyperphosphorylation of the PU.1 protein.
      HQ-induced alterations in PU.1-DNA binding are concomitant with a sustained
      immature CD34(+) phenotype and cytokine-dependent enhanced clonogenic activity in
      cultured human HPC. These results suggest that HQ induces a dysregulation in the
      external signals modulating PU.1 protein phosphorylation and this dysregulation
      may be an early event in the generation of benzene-induced AML.

PMID- 16642265
TI  - Effect of cosmological neutrinos on discrimination between the two enantiomers of
      a chiral molecule.
AB  - In the framework of an extraterrestrial origin of biological homochirality,
      universal mechanisms are of particular interest. In this sense we consider the
      weak parity-violating neutrino-electron interaction through weak charged currents
      W (+/-) between the relic flux of cosmological neutrinos and the electrons of a
      chiral molecule. We use the known theoretical result of the split in energy of
      the two helicity sates of an electron in the cosmic neutrino bath, due to weak
      charged currents. In the case that electrons of a chiral molecule are submitted
      to a helicoidal potential due to the nuclear conformation, these electrons have
      opposite helicities for the two enantiomers of the molecule and consequently the
      mentioned neutrino-electron interaction would produce a splitting in energy
      between the two enantiomers. An estimation of this energy for the case of a
      single electron yields a small value of the order of 10(-26) eV. This value
      results amplified by the contribution of all the molecular electrons having
      helicity and other possible mechanisms.

PMID- 16642266
TI  - Surfactant assemblies and their various possible roles for the origin(s) of life.
AB  - A large number of surfactants (surface active molecules) are chemically simple
      compounds that can be obtained by simple chemical reactions, in some cases even
      under presumably prebiotic conditions. Surfactant assemblies are self-organized
      polymolecular aggregates of surfactants, in the simplest case micelles, vesicles,
      hexagonal and cubic phases. It may be that these different types of surfactant
      assemblies have played various, so-far underestimated important roles in the
      processes that led to the formation of the first living systems. Although nucleic
      acids are key players in the formation of cells as we know them today (RNA world
      hypothesis), it is still unclear how RNA could have been formed under prebiotic
      conditions. Surfactants with their self-organizing properties may have assisted,
      controlled and compartimentalized some of the chemical reactions that eventually
      led to the formation of molecules like RNA. Therefore, surfactants were possibly
      very important in prebiotic times in the sense that they may have been involved
      in different physical and chemical processes that finally led to a transformation
      of non-living matter to the first cellular form(s) of life. This hypothesis is
      based on four main experimental observations: (i) Surfactant aggregation can lead
      to cell-like compartimentation (vesicles). (ii) Surfactant assemblies can provide
      local reaction conditions that are very different from the bulk medium, which may
      lead to a dramatic change in the rate of chemical reactions and to a change in
      reaction product distributions. (iii) The surface properties of surfactant
      assemblies that may be liquid- or solid-like, charged or neutral, and the
      elasticity and packing density of surfactant assemblies depend on the chemical
      structure of the surfactants, on the presence of other molecules, and on the
      overall environmental conditions (e. g. temperature). This wide range of surface
      characteristics of surfactant assemblies may allow a control of surface-bound
      chemical reactions not only by the charge or hydrophobicity of the surface but
      also by its "softness". (iv) Chiral polymolecular assemblies (helices) may form
      from chiral surfactants. There are many examples that illustrate the different
      roles and potential roles of surfactant assemblies in different research areas
      outside of the field of the origin(s) of life, most importantly in investigations
      of contemporary living systems, in nanotechnology applications, and in the
      development of drug delivery systems. Concepts and ideas behind many of these
      applications may have relevance also in connection to the different unsolved
      problems in understanding the origin(s) of life.

PMID- 16642267
TI  - Thermal energy and the origin of life.
AB  - Life has evolved on Earth with electromagnetic radiation (light), fermentable
      organic molecules, and oxidizable chemicals as sources of energy. Biological use
      of thermal energy has not been observed although heat, and the thermal gradients
      required to convert it into free energy, are ubiquitous and were even more
      abundant at the time of the origin of life on Earth. Nevertheless, Earth
      organisms sense thermal energy, and in suitable environments may have gained the
      capability to use it as energy source. It has been proposed that the first
      organisms obtained their energy by a first protein named pF(1) that worked on a
      thermal variation of the binding change mechanism of today's ATP sythase enzyme.
      Organisms using thermosynthesis may still live where light or chemical energy
      sources are not available. Possible suitable examples are subsurface environments
      on Earth and in the outer Solar System, in particular the subsurface oceans of
      the icy satellites of Jupiter and Saturn.

PMID- 16642268
TI  - Abiotic condensation synthesis of glyceride lipids and wax esters under simulated
      hydrothermal conditions.
AB  - Precursor compounds for abiotic proto cellular membranes are necessary for the
      origin of life. Amphipathic compounds such as fatty acids and acyl glycerols are
      important candidates for micelle/bilayer/vesicle formation. Two sets of
      experiments were conducted to study dehydration reactions of model lipid
      precursors in aqueous media to form acyl polyols and wax esters, and to evaluate
      the stability and reactions of the products at elevated temperatures. In the
      first set, mixtures of n-nonadecanoic acid and ethylene glycol in water, with and
      without oxalic acid, were heated at discrete temperatures from 150 ( composite
      function)C to 300 ( composite function)C for 72 h. The products were typically
      alkyl alkanoates, ethylene glycolyl alkanoates, ethylene glycolyl bis-alkanoates
      and alkanols. The condensation products had maximum yields between 150 (
      composite function)C and 250 ( composite function)C, and were detectable and thus
      stable under hydrothermal conditions to temperatures < 300 ( composite
      function)C. In the second set of experiments, mixtures of n-heptanoic acid and
      glycerol were heated using the same experimental conditions, with and without
      oxalic acid, between 100 ( composite function)C and 250 ( composite function)C.
      The main condensation products were two isomers each of monoacylglycerols and
      diacylglycerols at all temperatures, as well as minor amounts of the fatty acid
      anhydride and methyl ester. The yield of glyceryl monoheptanoates generally
      increased with increasing temperature and glyceryl diheptanoates decreased
      noticeably with increasing temperature. The results indicate that condensation
      reactions and abiotic synthesis of organic lipid compounds under hydrothermal
      conditions occur easily, provided precursor concentrations are sufficiently high.

PMID- 16642269
TI  - Pelvic organ prolapse and measurements of the pelvic floor.

PMID- 16642271
TI  - A measles virus vaccine strain derivative as a novel oncolytic agent against
      breast cancer.
AB  - Breast cancer is the most common malignancy and the second leading cause of
      female cancer mortality in the United States. There is an urgent need for
      development of novel therapeutic approaches. In this study, we investigated the
      antitumor potential of a novel viral agent, an attenuated strain of measles virus
      deriving from the Edmonston vaccine lineage, genetically engineered to produce
      carcinoembryonic antigen (CEA) against breast cancer. CEA production as the virus
      replicates can serve as a marker of viral gene expression. Infection of a variety
      of breast cancer cell lines including MDA-MB-231, MCF7 and SkBr3 at different
      multiplicities of infection (MOIs) from 0.1 to 10 resulted in significant
      cytopathic effect consisting of extensive syncytia formation and massive cell
      death at 72-96 h from infection. All breast cancer lines overexpressed the
      measles virus receptor CD46 and supported robust viral replication, which
      correlated with CEA production. TUNEL assays indicated an apoptotic mechanism of
      syncytial death. The efficacy of this approach in vivo was examined in a
      subcutaneous Balb C/nude mouse model of MDA-MB-231 cells. Intravenous
      administration of MV-CEA at a total dose of 1.2 x 10(7) TCID50 resulted in
      statistically significant tumor growth delay ( p=0.005) and prolongation of
      survival ( p=0.001). In summary, MV-CEA has potent antitumor activity against
      breast cancer lines and xenografts. Monitoring marker peptide levels in the serum
      could serve as a low-risk method of detecting viral gene expression during
      treatment and could allow dose optimization and individualization of treatment.
      Trackable measles virus derivatives merit further exploration in breast cancer
      treatment.

PMID- 16642275
TI  - Twin gestation pregnancies: genetic counseling and testing experience.
AB  - We report on the prenatal genetic counseling and testing experience in 343
      pregnancies with twin or higher multiple gestations. By self-report, 8% (27/343)
      parents of these pregnancies reported meeting with a genetic counselor, and 23%
      (79/343) elected prenatal genetic testing. The most common testing procedures
      elected were maternal serum analyte screening and amniocentesis to identify
      fetuses with aneuploidy or neural tube defects. Use of prenatal genetic testing
      was correlated with advanced maternal age. No association was found between use
      of genetic testing and use of OI/ART or the length of time needed to conceive.
      Forty percent (11/27) of those who met with a genetic counselor opted to decline
      prenatal testing/screening. These data suggest that although clients with
      multiple gestation pregnancies would likely benefit from genetic counseling, many
      are not availing themselves of this service. Implications of these data for the
      genetic counseling profession are discussed.

PMID- 16642277
TI  - Anatomical variations of the hepatic artery: study of 932 cases in liver
      transplantation.
AB  - The aim of this study was to identify and to classify anatomical hepatic artery
      (HA) variations concerning 932 HA dissections in liver transplantation (LT).
      Normal HA distribution was found in 68.1%. Variations of HA were detected in
      31.9% and were divided into three groups describing 48 common hepatic artery
      (CHA) anomalies, 236 left or right hepatic artery (RHA) anomalies and 13 rare
      variations including one case of RHA stemmed from the inferior mesenteric artery
      and one case of normal CHA passed behind the portal vein. The authors propose a
      modified classification for HA anomalies which are based on the origin of the
      hepatic arterial supply (either by the CHA as the only source of the arterial
      vascularization or by additional or replaced right and left arteries) in order to
      improve management of liver disease thus as in LT.

PMID- 16642278
TI  - Mental foramen in Thais: an anatomical variation related to gender and side.
AB  - Sixty-nine adult mandibles (45 male, 24 female) of Thai dry skulls were assessed
      to determine the size, the orientation and the location of the mental foramen
      (MF) related to gender and side. The results showed that the usual direction of
      exit of the MF was in a posterosuperior direction. The most common location of
      the MF was bilaterally symmetrical and located on the same vertical line with the
      long axis of the lower second premolar. The mean distances from the MF to the
      symphysis menti (A), to the posterior border of the mandibular ramus (P), to the
      lower border of the mandible (mb) and to the buccal cusp tip of the second
      premolar (cm) were 28.83, 68.85, 14.88 and 24.27 mm, respectively. The mean
      distances from the alveolar bone crest across the MF to the lower border of the
      mandible (ab) was 29.97 mm. The mean distance from the buccal cusp tip of the
      second premolar through the long axis of the clinical crown to the lower border
      of the mandible (cb) was 39.18 mm. No measurements varied according to the sides
      (P > 0.05). In contrast, gender differences were significant in all measurements
      with the longer distances in males (P < 0.05). The mean ratios of A/(A + P),
      mb/ab and cm/cb in all subjects were 0.30, 0.50 and 0.62, respectively. The
      values of the three ratios were nearly equal in males and females. Our results
      may assist surgeons to localize important maxillofacial neurovascular bundles
      passing through the MF in avoiding complication from local anesthetic, surgical
      and other invasive procedures.

PMID- 16642279
TI  - Anatomy of lateral ankle ligaments and their relationship to bony landmarks.
AB  - This study was designed to determine and describe precise anatomy of the lateral
      ankle ligaments and their relationship to adjacent osseous structures. This study
      was performed on 42 legs of 22 adult human embalmed cadavers. The lateral ankle
      ligaments were carefully dissected using a 2.5x surgical loupe. Mean values for
      the length, width and angle of the individual lateral ankle ligaments were
      measured. The precise location of insertion points and course of each ligament
      was observed and noted with ankle placed in neutral position. The anterior
      talofibular and calcaneofibular ligaments were coated with radio-opaque material.
      Radiographs were then taken in the anteroposterior, mortise and lateral
      projections. The anterior talofibular ligament (ATFL) was a flat, quadrilateral
      ligament and it made mean angle of 25 degrees (range 5 degrees -45 degrees ) with
      horizontal plane, and a mean angle of 47 degrees (range 45 degrees -56 degrees )
      with sagittal plane. The posterior talofibular ligament was oriented in a nearly
      horizontal plane. Calcaneofibular ligament (CFL) was a flat oval ligament. It
      made a mean angle of 40 degrees (range 30 degrees -58 degrees ) with horizontal
      plane, and mean angle of 51 degrees (range 32 degrees -60 degrees ) with sagittal
      plane. The angle between CFL and ATFL was approximately 132 degrees (range 118
      degrees -145 degrees ). These data provides important information for diagnosing
      injury and reconstructing lateral ankle ligaments.

PMID- 16642280
TI  - Rare variation in course and affluence of internal iliac vein due to its
      anatomical and surgical significance.
AB  - During regular dissection of the retroperitoneal region, three uncommon
      anatomical variations of the internal iliac veins were found on dissected
      specimens: in the first case, the internal iliac veins converge forming a common
      trunk draining into the left external iliac vein. In the other two cases, the
      internal iliac vein crosses the median plane and flows into the contralateral
      common iliac vein. These anomalies result from a persistence of the embryonic
      inferior branch of the cardinal vein and are important to be known for they may
      be undetected or may not appear in imaging. These data have implications for both
      pelvic surgeons and anatomists who manipulated this anatomical area.

PMID- 16642281
TI  - A morphometric study on the superficial palmar arch of the hand.
AB  - The vascular anatomy of the hand is a complex and challenging area and has been
      the subject of many studies. Knowledge of the vascular patterns and diameters of
      the hand gained more importance with improvements in microsurgical techniques in
      reconstructive hand surgery. We evaluated 50 hands (26 left, 24 right) of 26
      formalin preserved cadavers to determine the superficial palmar arch, its
      branches and contributing vessels with special attention to the diameters. The
      symmetry of the types was also evaluated in detail for the first time in the
      literature. Measurements were made with the help of a digital caliper. The
      diameters of the ulnar, radial and median arteries were taken at the level of the
      wrist while the common palmar digital arteries, hypothenar branches and the
      superficial palmar branch of the radial artery were measured at their origin. Two
      types of superficial palmar arch were found and defined as complete (43/50 hands)
      and incomplete arches (7/50 hands). The complete arches were divided into four
      subgroups and incomplete arches into three subgroups. Most cases were found at
      the complete AI group (17 hands). Comparison of the arterial diameters showed the
      ulnar artery was the dominant vessel of the palm. The diameters of the common
      palmar digital arteries were not different with regard to complete or incomplete
      arches and between both sides. It looks safe to sacrifice one of the radial or
      ulnar arteries in some arterial interventions including radial artery
      cannulation, radial forearm flap and radial or ulnar artery harvesting for bypass
      grafting if the arch is complete. But we still recommend the noninvasive tests
      like modified Allen test or Doppler ultrasonography, before performing an
      invasive arterial intervention. We propose the radiologists to incorporate the
      median artery into the Doppler dynamic test in particular the existence or the
      absence of anastomoses between radial and ulnar arteries.

PMID- 16642286
TI  - Duplex ultrasound verified by angiography in patients with severe primary and
      restenosis of internal carotid artery.
AB  - There are very limited data in the literature about the reliability of duplex
      ultrasound (DU) verified by angiography in patients with restenosis of the
      internal carotid artery (ICA) after carotid surgery compared with primary carotid
      artery stenosis patients. Our objective was to compare the reliability of DU
      verified by conventional angiography in the diagnosis of severe primary stenosis
      versus restenosis of ICA. One hundred thirty-four patients (238 arteries) were
      examined by both DU and angiography. Severe stenosis (>70%) was found in 47
      primary stenotic arteries and in 70 restenotic arteries. Accuracy, specificity,
      sensitivity, positive predictive value (PPV), and negative predictive value were
      obtained for basic DU criteria after verification of ultrasound data by
      angiography. The best accuracy for detection of >70% stenosis by end diastolic
      velocity was found for the velocity of 70 cm/sec or more in both groups, but
      accuracy for the restenosis group was significantly higher (96.9% vs. 89.8%, p =
      0.025). Additionally, specificity (p = 0.01) and PPV (p = 0.01) were
      significantly higher in the restenosis group. The best accuracy for detection of
      >70% stenosis by peak systolic velocity was found for the velocity of 220 cm/sec
      or more for restenoses and 200 cm/sec or more for primary stenoses. The accuracy
      of the ultrasound was significantly higher in the restenosis group (94.6% vs.
      87%, p = 0.04), as were specificity (p = 0.01) and PPV (p = 0.02). The diagnosis
      of severe restenosis by DU is reliable and can be used for decision making
      regarding surgery or stenting without angiography. In patients with Doppler
      parameters pointing to borderline moderate/severe primary carotid stenosis and
      technically complicated cases, angiography in addition to sonography before
      surgery is recommended.

PMID- 16642288
TI  - Deletion of SLC19A2, the high affinity thiamine transporter, causes selective
      inner hair cell loss and an auditory neuropathy phenotype.
AB  - Mutations in the gene coding for the high-affinity thiamine transporter Slc19a2
      underlie the clinical syndrome known as thiamine-responsive megaloblastic anemia
      (TRMA) characterized by anemia, diabetes, and sensorineural hearing loss. To
      create a mouse model of this disease, a mutant line was created with targeted
      disruption of the gene. Cochlear function is normal in these mutants when
      maintained on a high-thiamine diet. When challenged with a low-thiamine diet,
      Slc19a2-null mice showed 40-60 dB threshold elevations by auditory brainstem
      response (ABR), but only 10-20 dB elevation by otoacoustic emission (OAE)
      measures. Wild-type mice retain normal hearing on either diet. Cochlear
      histological analysis showed a pattern uncommon for sensorineural hearing loss:
      selective loss of inner hair cells after 1-2 weeks on low thiamine and
      significantly greater inner than outer hair cell loss after longer low-thiamine
      challenges. Such a pattern is consistent with the observed discrepancy between
      ABR and OAE threshold shifts. The possible role of thiamine transport in other
      reported cases of selective inner hair cell loss is considered.

PMID- 16642296
TI  - Growing phototrophic cells without light.
AB  - Many phototrophic microorganisms contain large quantities of high-value products
      such as n-3 polyunsaturated fatty acids and carotenoids but phototrophic growth
      is often slow due to light limitation. Some phototrophic microorganisms can also
      grow on cheap organic substrate heterotrophically. Heterotrophic cultivation can
      be well controlled and provides the possibility to achieve fast growth and high
      yield of valuable products on a large scale. Several strategies have been
      investigated for cultivation of phototrophic microorganisms without light. These
      include trophic conversion of obligate photoautotrophic microorganisms by genetic
      engineering, development of efficient cultivation systems and optimization of
      culture conditions. This paper reviews recent advances in heterotrophic
      cultivation of phototrophic cells with an emphasis on microalgae.

PMID- 16642297
TI  - Molecular characterization of a bacterial consortium enriched from an oilfield
      that degrades phenanthrene.
AB  - Characterization of functional and phylogenetic genes was carried out on a
      bacterial consortium, enriched from a water treatment system of an oilfield, that
      could use phenanthrene as the sole carbon source. The mixed culture degraded 130
      mg phenanthrene l(-1) in 16 days, which is significantly faster than previously
      reported pure cultures. The existence of catabolic genes (nahAc, C23O) in the
      mixed culture was quantitated by most probable number PCR. The plasmid encoding
      phenanthrene catabolic genes increased relative to the chromosome genes.
      Heterogeneous bacteria were present according to both PCR denaturing gradient gel
      electrophoresis and cloning methods, suggesting the possible existence of
      cooperation between different biochemical PAH-transforming pathways.

PMID- 16642298
TI  - Co-production of schizophyllan and arabinoxylan from corn fiber.
AB  - Schizophyllum commune strain ATCC 38548 grew well on a medium containing alkaline
      H2O2 -pretreated corn fiber as a sole carbon source, and clarified the culture
      medium within 7 days. The strain preferentially utilized the starch component of
      corn fiber for growth and production of schizophyllan. Culture supernatants
      contained approx. 50 mg schizophyllan and 200 mg arabinoxylan per g corn fiber.
      These polysaccharides were recovered separately by differential precipitation
      with ethanol.

PMID- 16642299
TI  - Production of bioactive human beta-defensin-3 in Escherichia coli by soluble
      fusion expression.
AB  - A codon optimized mature human beta-defensin-3 gene (smHBD3) was synthesized and
      fused with TrxA to construct pET32-smHBD3 vector, which was transformed into E.
      coli BL21(DE3) and cultured in MBL medium. The volumetric productivity of fusion
      protein reached 0.99 g fusion protein l(-1), i.e. 0.21 g mature HBD3 l(-1).
      Ninety-six percentage of the fusion protein was in a soluble form and constituted
      about 45% of the total soluble protein. After cell disruption, the soluble fusion
      protein was separated by affinity chromatography and cleaved by enterokinase, and
      then the mature HBD3 was purified by cationic ion exchange chromatography. The
      overall recovery ratio of HBD3 was 43%. The purified mature HBD3 demonstrated
      antimicrobial activity against E. coli.

PMID- 16642300
TI  - Properties of laccases produced by Pycnoporus sanguineus induced by 2,5-xylidine.
AB  - Two isoforms of laccase produced from the culture supernatant of Pycnoporus
      sanguineus were partially purified by phenyl-Sepharose chromatography. Molecular
      masses of the enzymes were 80 kDa (Lac I) and 68 kDa (Lac II). Optimum activity
      of Lac I was at pH 4.8 and 30 degrees C, and Lac II was at pH 4.2 and 50 degrees
      C over 5 min reaction. The Km values of enzymes toward syringaldazine were 10
      microM: (Lac I) and 8 microM: (Lac II). Sodium azide inhibited Lac I (85%) and
      Lac II (75%) activities.

PMID- 16642301
TI  - Lipase-mediated transformation of vegetable oils into biodiesel using propan-2-ol
      as acyl acceptor.
AB  - Propan-2-ol was used as an acyl acceptor for immobilized lipase-catalyzed
      preparation of biodiesel. The optimum conditions for transesterification of crude
      jatropha (Jatropha curcas), karanj (Pongamia pinnata) and sunflower (Helianthus
      annuus) oils were 10% Novozym-435 (immobilized Candida antarctica lipase B) based
      on oil weight, alcohol to oil molar ratio of 4:1 at 50 degrees C for 8 h. The
      maximum conversions achieved using propan-2-ol were 92.8, 91.7 and 93.4% from
      crude jatropha, karanj and sunflower oils, respectively. Reusability of the
      lipase was maintained over 12 repeated cycles with propan-2-ol while it reached
      to zero by 7(th) cycle when methanol was used as an acyl acceptor, under standard
      reaction conditions.

PMID- 16642302
TI  - Relationship between poly-beta-hydroxybutyrate production and delta-endotoxin for
      Bacillus thuringiensis var. kurstaki.
AB  - A linear relationship between total solid concentration (TSC), delta-endotoxin
      production [Cry = 0.2795(TSC)-0.2472, R2 = 0.8644] and poly-beta-hydroxybutyrate
      (PHB) accumulation [PHB = 0.1327(TSC) + 0.3974, R2 = 0.9877] in Bacillus
      thuringiensis var. kurstaki HD-73 was observed. A similar correlation between
      delta-endotoxin and PHB accumulation [Cry = 2.1573(PHB)-1.1248, R2 = 0.9181] was
      found. A minimum PHB accumulation of 0.52 mg l(-1) was required before the onset
      of delta-endotoxin production.

PMID- 16642303
TI  - Production of a cellulase in silkworm larvae using a recombinant Bombyx mori
      nucleopolyhedrovirus lacking the virus-encoded chitinase and cathepsin genes.
AB  - The expression efficiency of an insect-derived cellulase was assayed in silkworm
      larvae infected with recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) mutants
      lacking the virus-encoded chitinase (chiA) and/or cathepsin (v-cath) genes.
      Expression was increased by approx. 10% in mutants lacking chiA or v-cath and 17%
      in a mutant lacking both chiA and v-cath compared with that of the unmodified
      recombinant BmNPV. The recombinant BmNPV lacking both chiA and v-cath can
      therefore be used for a large-scale production of foreign proteins in silkworms.

PMID- 16642304
TI  - Influence of dimethyl sulfoxide on extracellular enzyme production by Pleurotus
      ostreatus.
AB  - Dimethyl sulfoxide (DMSO) is commonly used as a co-solvent to dissolve poorly
      water-soluble biologically active agents to assess their biological activities
      such as for enzyme induction. The question addressed was whether DMSO can be
      assumed to be an inert co-solvent. The influence of DMSO on the production of
      extracellular enzymes by Pleurotus ostreatus was investigated. DMSO functioned as
      either an inducer or a repressor, depending on the enzyme studied. The production
      of laccase and endo-1,4-beta-xylanase increased by 29 and 250%, respectively, in
      presence of DMSO. However, DMSO repressed the activities of manganese peroxidase,
      beta-glucosidase, beta-xylanase, and endo-1,4-beta-glucanase by 30, 33, 99 and
      16%, respectively. These results raise concerns about the interpretation of
      bioactivity measurements when DMSO is assumed to function as an inert co-solvent
      to solubilize water-insoluble molecules.

PMID- 16642305
TI  - Characterization of a new stearoyl-acyl carrier protein desaturase gene from
      Jatropha curcas.
AB  - A new full-length cDNA of stearoyl-acyl carrier protein desaturase was obtained
      by RT-PCR and RACE techniques from developing seeds of Jatropha curcas. Sequence
      alignment showed that its deduced amino acid sequence had high similarity with
      other stearoyl-acyl carrier protein desaturases. The gene was functionally
      expressed in E. coli and the desaturating activity of recombinant protein was
      easily detected when assayed in vitro with added spinach ferredoxin. Southern
      blot analysis indicated that the gene was a member of a small gene family.
      Northern blot analysis revealed it was highly expressed in developing fruits of
      J. curcas.

PMID- 16642306
TI  - Fermentation of 12% (w/v) glucose to 1.2 M lactate by Escherichia coli strain
      SZ194 using mineral salts medium.
AB  - A non-recombinant mutant of Escherichia coli B, strain SZ194, was developed that
      produces over 1 M D-lactate from glucose (or sucrose) in 72 h using mineral salts
      medium supplemented with 1 mM: betaine in simple anaerobic fermentations. Rates
      and yields were highest at pH 7.5. Yields approached the theoretical maximum with
      only trace amounts of co-products. Chiral purity of D-lactate was estimated to be
      95%. Specific and volumetric productivities for SZ194 in mineral salts medium (pH
      7.5) with betaine were equivalent to those in Luria broth.

PMID- 16642307
TI  - Betaine tripled the volumetric productivity of D(-)-lactate by Escherichia coli
      strain SZ132 in mineral salts medium.
AB  - Osmotic stress restricts glycolytic flux, growth (rate and yield), D-lactate
      productivity, and D-lactate tolerance in Escherichia coli B strain SZ132 during
      batch fermentation in mineral salts medium with 10% (w/v) sugar. Addition of 1
      mM: betaine, a non-metabolized protective osmolyte, doubled cell yield, increased
      specific productivity of D-lactate and glycolytic flux by 50%, and tripled
      volumetric productivity (from 8.6 to 25.7 mmol l(-1) h(-1); 0.8 to 2.3 g l(-1) h(
      1)). Glycolytic flux and specific productivity in mineral salts medium with
      betaine exceeded that in Luria broth, substantially eliminating the need for
      complex nutrients during D-lactate production. In mineral salts medium
      supplemented with betaine, SZ132 produced approximately 1 mol D-lactate (90 g)
      per 100 g sugar (glucose or sucrose).

PMID- 16642310
TI  - Inverse correlation between the formation of mitochondria-derived vacuoles and
      Lewy-body-like hyaline inclusions in G93A superoxide-dismutase-transgenic mice.
AB  - In G93A mice, the most popular model of amyotrophic lateral sclerosis (ALS),
      neuronal Lewy-body-like hyaline inclusions (LBHIs) and mitochondria-derived
      vacuoles are observed in addition to motor neuron loss. Although LBHIs are
      thought to be toxic, the significance of the mitochondria-derived vacuoles has
      not been fully investigated. In this study, the relationship between the
      formation of these vacuoles and LBHIs was clarified statistically in the lumbar
      segment from two phyletic lines of G93A mice (G1L, G1H), using
      immunohistochemical methods. Furthermore, the distributions of vacuoles and LBHIs
      were examined in the pons including the facial nucleus, where pathological
      changes occur in ALS patients and G93A mice. Numerous vacuoles 2-3 microm in
      diameter were detected in the neuropil of the lumbar segment from G1L mice
      euthanatized approximately 3.5 months prior to the onset of the disease. Most of
      the vacuoles disappeared, but some became larger as the disease progressed. The
      number of vacuoles with a diameter exceeding 5 microm began to decrease after
      disease onset, while that of intra-neuritic LBHIs increased rapidly. There was a
      strong inverse correlation between the numbers of vacuoles and LBHIs in
      symptomatic mice (P<0.01; G1L, r=-0.91; G1H, r=-0.93). In the facial nucleus of
      G1L mice, where the number of motor neurons was significantly reduced, only a few
      LBHIs were detected along with prominent vacuole formation. In contrast,
      significantly more LBHIs with little vacuole formation were evident around the
      facial nucleus in G1L mice. Furthermore, the SOD1 immunoreactivity in vacuoles
      initially increased and then decreased after disease onset. Taken together, the
      present findings suggest that the mitochondria-derived vacuoles might prevent the
      formation of LBHIs by sequestering mutated SOD1 from the cytoplasm.

PMID- 16642311
TI  - The influences of tube voltage and scan direction on combined tube current
      modulation: a phantom study.
AB  - BACKGROUND: For the optimum application of tube current modulation in paediatric
      CT it is important to know the influences of different imaging parameters on it.
      OBJECTIVE: This phantom study was performed to evaluate the influences of tube
      voltage and scan direction on combined tube current modulation, which is a
      combination of angular and z-axis modulation. MATERIALS AND METHODS: Sixteen
      slice spiral CT with combined tube current modulation was performed using four
      different phantoms (one adult-size anthropomorphic phantom and three cone-shaped
      acryl phantoms) at three different tube voltages (80, 100 and 120 kVp) and two
      scan directions (craniocaudal and caudocranial). Effective tube current-time
      product (mAs) was chosen to maintain a consistent CTDIvol for each phantom. Other
      parameters, including detector collimation, slice width, pitch, reconstruction
      algorithm, scan field of view, and scan range were identical for each phantom.
      Changes in CTDIvol and mAs resulting from the modulation were calculated and
      compared. RESULTS: Changes in CTDIvol and mAs resulting from the modulation were
      different among the three tube voltages. In larger phantoms the greatest
      reductions (-6.1+/-3.9% in CTDIvol and -12.5+/-4.0% in mAs) were obtained with
      120 kVp, whereas in smaller phantoms they were obtained with 80 kVp (-2.8+/-0.9%
      in CTDIvol and -2.5+/-4.9% in mAs). Smaller CTDIvol (2.4+/-0.9 mGy vs. 2.5+/-1.0
      mGy, P=0.017) and mAs (57.2+/-40.4 mAs vs. 61.4+/-43.2 mAs, P=0.002) were used in
      caudocranial scans than in craniocaudal scans with the modulation. CONCLUSION:
      Combined tube current modulation is influenced by tube voltage and scan direction
      depending on phantom profile.

PMID- 16642313
TI  - The inter-trial effects of stimulus and saccadic direction on prosaccades and
      antisaccades, in controls and schizophrenia patients.
AB  - We investigated the influence of the direction of preceding saccadic trials on
      the latency of current prosaccades and antisaccades, in healthy subjects and
      patients with schizophrenia. When prosaccades and antisaccades were performed in
      separate, single-task blocks, we found that only prosaccades were delayed if the
      saccade in the prior trial was in the same direction, consistent with the
      expected directional effect from an 'inhibition of return'-like alternation
      advantage. However, both types of saccades were executed more quickly when the
      saccade in the penultimate trial was in the same direction, consistent with
      previous demonstrations of directional plasticity in monkeys. In blocks of
      randomly mixed prosaccades and antisaccades, the directional effects in healthy
      subjects were greatest when a prosaccade was preceded by an antisaccade,
      consistent with a summation of effects of alternation advantage (from the prior
      stimulus) and directional plasticity (from the prior saccade). Schizophrenic
      patients showed an additional phenomenon, a directionally specific inhibition of
      upcoming saccades by preceding antisaccades. These results suggest that saccades
      in humans are modulated by inter-trial effects attributable to both an
      'inhibition of return'-like alternation advantage and directional plasticity.

PMID- 16642314
TI  - Accuracy and underlying mechanisms of shifting movements in cellists.
AB  - Accuracy of shifting movements between two notes was examined in nine cellists
      (intermediate-professional skill levels). Three pairs of notes separated by
      different distances were tested under the same movement rate. Finger position on
      the string was measured by a circuit. Angular velocities of the left upper arm
      and forearm were measured by two angular velocity sensors; thus elbow angular
      velocity during shifts was estimated. Results showed that with increased elbow
      velocity and shifting distance endpoint variability stayed constant. The force of
      gravity assisted elbow extension during shifts toward higher pitched notes
      compared to flexion towards lower pitched notes, but faster movement velocity did
      not result in increased landing variability. Performance for note E on the A
      string was found to be less variable than other notes, suggesting that physical
      cue from the cello body geometry was used as a landmark for finger position.
      Cutaneous feedback from the thumb when hitting the body-neck junction enabled
      faster elbow extension velocity compared to shifts towards other notes. Cellists
      who showed higher performance accuracy also showed higher perceptual ability and
      performance proficiency. These results suggest that long-term over-training of
      fast and accurate movements enables musicians to maintain accuracy and
      variability across different movement distances and velocities. Higher perceptual
      ability and performance proficiency are correlated with increased accuracy but
      not lower variability, indicating although perceptual ability and performance
      proficiency are important for pitch accuracy, movement variability is still
      constrained by the capacity of the motor system, which is highly fine-tuned and
      different than non-musicians.

PMID- 16642315
TI  - Experimental muscle pain does not affect fine motor control of the human hand.
AB  - Conditions known to cause hand pain, such as arthritis, are often accompanied by
      impaired dexterity. The aim of this study was to determine whether this
      association is coincident, or whether pain affects dexterity directly. In the
      first part of the study, several tests of dexterity based on pegboard skills were
      compared with a precision-grip-lift task: the correlations between the results of
      any of these tests were not significant at the 0.01 level. Nineteen subjects were
      then tested with a modified Purdue pegboard test and the precision grip-lift
      task, both without pain and during pain induced by injection of 5% hypertonic
      saline into the first dorsal interosseous muscle of the non-dominant hand. There
      was no significant difference in the performance of either task when the muscle
      was painful, indicating that acute experimental muscle pain does not affect
      dexterity.

PMID- 16642316
TI  - Delayed onset muscle soreness at tendon-bone junction and muscle tissue is
      associated with facilitated referred pain.
AB  - Delayed onset muscle soreness (DOMS) involves central and peripheral pain
      mechanisms. Referred pain patterns following stimulation of DOMS affected tissue
      have not been fully described. Referred pain may provide information on how
      central mechanisms are involved in DOMS, as referred pain is a central mechanism.
      Further, tendon tissue involvement in DOMS is not clear. This study assessed
      pressure pain threshold (PPT) sensitivity at the tendon, tendon-bone junction
      (TBJ) and muscle belly sites of tibialis anterior pre- and during DOMS in 45
      subjects (34 males, 11 females). Furthermore, pain and referred pain areas at
      these three sites in response to hypertonic saline injection (n = 15 per
      injection site) were investigated pre- and during DOMS. DOMS was induced using
      controlled plantarflexion from a platform (bodyweight as resistance) causing
      eccentric contraction of the tibialis anterior muscle. DOMS induced PPT decrease
      was found at the TBJ and muscle belly sites only (P < 0.001). No mechanical
      effect was found in the unexercised limb. Maximal pain intensity induced by
      hypertonic saline given pre-DOMS was significantly higher for the tendon and TBJ
      injections compared to intramuscular injections (P < 0.05). Significantly higher
      referred pain frequency and enlarged pain areas were found at the muscle belly
      and TBJ sites following injection during DOMS compared to pre-DOMS. The results
      indicate that muscle belly and TBJ sites are sensitised while tendon tissue per
      se is unaffected by DOMS. Central sensitivity changes caused by DOMS may explain
      the increase in referred pain frequency and enlarged pain areas.

PMID- 16642318
TI  - Patients' attitudes on how to deal with the risk of future stone recurrences.
AB  - One hundred consecutive patients referred for active stone removal responded to a
      number of questions regarding their attitude to metabolic risk evaluation and
      recurrence prevention. Of the 74 men and 26 women all but one were interested in
      the cause of their disease. While 95% of the patients were motivated to change
      their dietary habits, only 71% were interested in pharmacological treatment.
      Collection of 24-h urine for risk evaluation in one or five fractions was
      acceptable to 94 and 84% of the patients, respectively. Only 79% wanted to
      collect urine during more than one 24-h period. Given the option of a recurrence
      prevention programme or active stone removal when or if a stone appeared,
      approximately half of our patients (52%) chose the first, and about one-third
      (29%) of them chose the second alternative, whereas as many as 19% of the
      patients did not express any opinion. A programme for regular follow-up in order
      to detect new stones early was appreciated by only 81 patients. These results
      show that biochemical risk evaluation and recurrence prevention is generally met
      with a positive attitude by most patients and that medical recurrence prevention
      appears to be appreciated by more than half of the patients.

PMID- 16642319
TI  - Environmental and genetic effects on the formation of ectomycorrhizal and
      arbuscular mycorrhizal associations in cottonwoods.
AB  - Although both environment and genetics have been shown to affect the mycorrhizal
      colonization of host plants, the impacts of these factors on hosts that can be
      dually colonized by both ectomycorrhizal (EM) and arbuscular mycorrhizal (AM)
      fungi are less understood. We examined the influence of environment and host
      crosstype on the EM and AM colonization of cottonwoods (Populus angustifolia and
      natural hybrids) by comparing levels of colonization of trees growing in common
      gardens that differed in elevation and soil type. We also conducted a
      supplemental watering experiment to determine the influence of soil moisture on
      AM and EM colonization. Three patterns emerged. First, garden location had a
      significant impact on mycorrhizal colonization, such that EM colonization was 30%
      higher and AM colonization was 85% lower in the higher elevation garden than the
      lower elevation garden. Second, crosstype affected total (EM + AM) colonization,
      but did not affect EM or AM colonization. Similarly, a significant garden x
      crosstype interaction was found for total colonization, but not for EM or AM
      colonization. Third, experimental watering resulted in 33% higher EM colonization
      and 45% lower AM colonization, demonstrating that soil moisture was a major
      driver of the mycorrhizal differences observed between the gardens. We conclude
      that environment, particularly soil moisture, has a larger influence on
      colonization by AM versus EM fungi than host genetics, and suggest that
      environmental stress may be a major determinant of mycorrhizal colonization in
      dually colonized host plants.

PMID- 16642322
TI  - Percutaneous reconstruction of the innominate bifurcation using the retrograde
      'kissing stents' technique.
AB  - INTRODUCTION: Obstructions of the supraaortic vessels are an important cause of
      morbidity associated with a variety of symptoms. Percutaneous transluminal
      angioplasty has evolved as an effective and safe treatment modality for occlusive
      lesions of the supraaortic vessels. However, the endovascular management of an
      innominate bifurcation has not previously been reported. METHODS: A 53-year-old
      female with a history of systematic hypertension, diabetes mellitus and
      hypercholesterolemia presented with left hemiparesis and dysarthria. Angiography
      of the innominate artery showed a stenosis of the innominate bifurcation.
      RESULTS: The lesion was successfully treated using the retrograde kissing stent
      technique via a brachial approach and an exposed direct carotid approach.
      CONCLUSION: The retrograde kissing stent technique for the treatment of a
      stenosis of the innominate bifurcation was found to be a safe and effective
      alternative to conventional surgery.

PMID- 16642324
TI  - Minimally invasive treatment of C2 odontoid traumatic fracture with transoral
      percutaneous vertebroplasty.

PMID- 16642325
TI  - Multicontrast-weighted magnetic resonance imaging of atherosclerotic plaques at
      3.0 and 1.5 Tesla: ex-vivo comparison with histopathologic correlation.
AB  - The purpose was to analyze magnetic resonance (MR) plaque imaging at 3.0 Tesla
      and 1.5 Tesla in correlation with histopathology. MR imaging (MRI) of the
      abdominal aorta and femoral artery was performed on seven corpses using T1
      weighted, T2-weighted, and PD-weighted sequences at 3.0 and 1.5 Tesla. Cross
      sectional images at the branching of the inferior mesenteric artery and the
      profunda femoris were rated with respect to image quality. Corresponding cross
      sections of the imaged vessels were obtained at autopsy. The atherosclerotic
      plaques in the histological slides and MR images were classified according to the
      American Heart Association (AHA) and analyzed for differences. MRI at 3.0 Tesla
      offered superior depiction of arterial wall composition in all contrast
      weightings, rated best for T2-weighted images. Comparing for field strength, the
      highest differences were observed in T1-weighted and T2-weighted techniques (both
      P< or =0.001), with still significant differences in PD-weighted sequence (P< or
      =0.005). The majority of plaques were histologically classified as calcified
      plaques. In up to 21% of the cases, MRI at both field strengths detected signal
      loss characteristic of calcification although calcified plaque was absent in
      histology. MRI at 3.0 Tesla offers superior plaque imaging quality compared with
      1.5 Tesla, but further work is necessary to determine whether this translates in
      superior diagnostic accuracy.

PMID- 16642326
TI  - A model for temporal resolution of multidetector computed tomography of coronary
      arteries in relation to rotation time, heart rate and reconstruction algorithm.
AB  - A model is presented that describes the image quality of coronary arteries with
      multidetector computer tomography. The results are discussed in the context of
      rotation time of the scanner, heart rate, and number of sectors used in the
      acquisition process. The blurring of the coronary arteries was calculated for
      heart rates between 50 and 100 bpm for rotation times of 420, 370, and 330 ms,
      and one-, two-, three-, and four-sector acquisition modes and irregular coronary
      artery movement is included. The model predicts optimal timing within the RR
      cycle of 45+/-3% (RCA), 44+/-4% and 74+/-6% (LCX), and 35+/-4% and 76+/-5% (LAD).
      The optimal timing shows a negative linear dependency on heart rate and increases
      with the number of sectors used. The RCA blurring decreases from 0.98 cm for 420
      ms, one-sector mode to 0.27 cm for 330 ms, four-sector mode. The corresponding
      values are 0.81 cm and 0.29 cm for LCX and 0.42 cm and 0.17 cm for LAD. The
      number of sectors used in a multisector reconstruction and the timing within the
      cardiac cycle should be adjusted to the specific coronary artery that has to be
      imaged. Irregular coronary artery movement of 1.5 mm justifies the statement that
      no more than two sectors should be used in multisector acquisition processes in
      order to improve temporal resolution in cardiac MDCT.

PMID- 16642327
TI  - Soft-tissue masses in the shoulder girdle: an imaging perspective.
AB  - We discuss the radiological assessment of soft-tissue masses presenting in the
      shoulder girdle and emphasise the relative strengths and weaknesses of the
      different imaging modalities available. The appearances of the common benign and
      malignant soft-tissue tumours are presented together with conditions that present
      with specific imaging features around the shoulder region.

PMID- 16642328
TI  - Basilar expansion of the human sphenoidal sinus: an integrated anatomical and
      computerized tomography study.
AB  - Basilar expansion of the sphenoidal sinus (BESS) was studied in order to
      demonstrate its critical relevance in endoscopic or microscopic endonasal
      surgical interventions, including access to the sphenoidal sinus itself or in
      transsphenoidal pituitary approaches. Direct evaluation of anatomical specimens
      (25 dry skulls and 25 formalin-fixed hemi heads) and the use of computerized
      tomography (CT) (50 dry skulls and 750 patients) showed a high BESS frequency
      (69%). The authors considered BESS to be critical when the posterior wall of the
      clivus was 2-mm thick and found a high incidence of this important anatomical
      variation (44%). This study also evaluated the relationship between the sinonasal
      septa, the clivus, and the internal carotid arteries, and a considerable
      regularity in the location of these structures was seen. The septa were
      anatomically related to the internal carotid arteries in 55% and to the clivus in
      33% of the cases. In conclusion, the high frequency of critical BESS here
      described is relevant to endoscopic or microscopic endonasal surgical
      interventions, including access to the sphenoidal sinus itself or in
      transsphenoidal pituitary approaches.

PMID- 16642329
TI  - Characterization of genes involved in the initial reactions of 4
      chloronitrobenzene degradation in Pseudomonas putida ZWL73.
AB  - The genes encoding enzymes involved in the initial reactions during degradation
      of 4-chloronitrobenzene (4CNB) were characterized from the 4CNB utilizer
      Pseudomonas putida ZWL73, in which a partial reductive pathway was adopted. A DNA
      fragment containing genes coding for chloronitrobenzene nitroreductase (CnbA) and
      hydroxylaminobenzene mutase (CnbB) were PCR-amplified and subsequently sequenced.
      These two genes were actively expressed in Escherichia coli, and recombinant E.
      coli cells catalyzed the conversion of 4CNB to 2-amino-5-chlorophenol, which is
      the ring-cleavage substrate in the degradation of 4CNB. Phylogenetic analyses on
      sequences of chloronitrobenzene nitroreductase and hydroxylaminobenzene mutase
      revealed that these two enzymes are closely related to the functionally
      identified nitrobenzene nitroreductase and hydroxylaminobenzene mutase from
      Pseudomonas strains JS45 and HS12. The nitroreductase from strain ZWL73 showed a
      higher specific activity toward 4CNB than nitrobenzene (approximately at a ratio
      of 1.6:1 for the recombinant or 2:1 for the wild type), which is in contrast to
      the case where the nitroreductase from nitrobenzene utilizers Pseudomonas
      pseudoalcaligenes JS45 with an apparently lower specific activity against 4CNB
      than nitrobenzene (0.16:1) [Kadiyala et al. Appl Environ Microbiol 69:6520-6526,
      2003]. This suggests that the nitroreductase from 4-chloronitrobenzene utilizer
      P. putida ZWL73 may have evolved to prefer chloronitrobenzene to nitrobenzene as
      its substrate.

PMID- 16642330
TI  - Metabolic activity of Corynebacterium glutamicum grown on L: -lactic acid under
      stress.
AB  - Respiration measurement in shake flasks is introduced as a new method to
      characterize the metabolic activity of microorganisms during and after stress
      exposure. The major advantage of the new method is the possibility to determine
      the metabolic activity independent of manual sampling without the necessity to
      change the culture vessel or the cultivation medium. This excludes stress
      factors, which may be induced by transferring the microorganisms to plates or
      respirometers. The negative influence, which interruptions of the shaker during
      sampling times may have on the growth of microorganisms was demonstrated. The
      applicability of the method was verified by characterizing the behavior of
      Corynebacterium glutamicum grown on the carbon source L: -lactic acid under
      stress factors such as carbon starvation, anaerobic conditions, lactic acid,
      osmolarity, and pH. The following conditions had no effect on the metabolic
      activity of C. glutamicum: a carbon starvation of up to 19 h, anaerobic
      conditions, lactic acid concentrations up to 10 g/l, 3-(N-morpholino)
      propanesulfonic acid buffer concentrations up to 42 g/l, or pH from 6.4 to 7.4.
      Lactic-acid concentrations from 10 to 30 g/l lead to a decrease of the growth
      rate and the biomass substrate yield without effecting the oxygen substrate
      conversion. Without adaptation, the organism did not grow at pH< or =5 or > or
      =9.

PMID- 16642331
TI  - Biodegradation of vinyl chloride and cis-dichloroethene by a Ralstonia sp. strain
      TRW-1.
AB  - An aerobic bacterium, Ralstonia sp. strain TRW-1, that assimilates vinyl chloride
      (VC) or ethene (ETH) as the sole carbon source was isolated from a chloroethene
      degrading enrichment culture. Phylogenetic analysis of 16S rDNA sequence of the
      isolate revealed almost 99% sequence similarity to Ralstonia pickettii. To our
      knowledge, this is the first report describing the isolation of a member of
      Ralstonia that can degrade VC as the growth substrate. The measured growth yield
      values for VC and ETH were 11.27 and 18.90 g protein/mole, respectively. The
      estimated half-velocity constant K (m) values for VC and ETH were 9.09+/-2.97 and
      5.73+/-2.96 muM, respectively. These values are almost three- to tenfold higher
      than for other VC-assimilating Mycobacterium sp. The strain also degrades cis
      dichloroethene (cis-DCE) in mineral salts medium containing yeast-extract, beef
      extract, casamino acids, or peptone. This ability of the strain TRW-1 to degrade
      cis-DCE in the presence of a nontoxic, water-soluble substrate is relevant to in
      situ remediation of cis-DCE-contaminated aquifers.

PMID- 16642332
TI  - Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas
      sp.: Production and structure elucidation.
AB  - The new marine Halomonas sp. strain GWS-BW-H8hM (DSM 17996) was found to produce
      3-(4'-hydroxyphenyl)-4-phenylpyrrole-2,5-dicarboxylic acid (HPPD-1) and 3,4
      bis(4'-hydroxy- phenyl)pyrrole-2,5-dicarboxylic acid (HPPD-2). In initial
      cultivations using marine broth, only low contents of these compounds have been
      isolated. Improving the conditions and growing the strain on artificial seawater
      supplemented with tryptone 10 g l(-1), yeast extract 5 g l(-1), L-tyrosine 0.6 g
      l(-1), glycine 1 g l(-1), and glucose 6 g l(-1), the growth-associated HPPD-1 and
      HPPD-2 production of a 40-l batch cultivation reached the amounts of 47 mg l(-1)
      and 116 mg l(-1), respectively, after 65 h. Both compounds showed potent anti
      tumor-promoting activities.

PMID- 16642333
TI  - Expression of Vitreoscilla hemoglobin enhances growth and levels of alpha-amylase
      in Schwanniomyces occidentalis.
AB  - A metabolic engineering approach was exploited to improve growth and protein
      secretion in the non-conventional yeast, Schwanniomyces occidentalis.
      Vitreoscilla hemoglobin (VHb) gene was expressed in S. occidentalis under the
      control of the native alpha-amylase (AMY1) promoter. Expression of VHb was
      confirmed by reverse transcriptase polymerase chain reaction and Western blot
      hybridization analysis. Effect of VHb on growth and protein secretion was studied
      in synthetic medium under both limiting and non-limiting dissolved oxygen
      conditions. Under both conditions, VHb-expressing cells exhibited higher oxygen
      uptake and higher specific growth rates. Levels of extracellular alpha-amylase
      were also elevated in the VHb-transformed strain relative to the control strain.
      In amylase production medium, VHb-expressing cells showed 3-fold elevated levels
      of alpha-amylase and a 31% increase in the total secreted protein under oxygen
      limiting environment. VHb was found to localize in the mitochondria in addition
      to its cytoplasmic location. Inhibition of respiration by antimycin A resulted in
      the loss of the growth-enhancing effects of VHb. A 2.5-fold increase in the
      cytochrome c oxidase (COX) activity was observed in VHb-expressing cells relative
      to the control. In addition to this, exogenously added VHb in the assay mixture
      augmented COX activity.

PMID- 16642334
TI  - Valence isomerization of 2-phospha-4-silabicyclo[1.1.0]butane: a high-level ab
      initio study.
AB  - The rearrangements for 2-phospha-4-silabicyclo[1.1.0]butane, analogous to the
      valence isomerization of the hydrocarbons bicyclobutane, 1,3-butadiene, and
      cyclobutene, were studied at the (U)QCISD(T)/6-311+G**//(U)QCISD/6-31G* level of
      theory. The monocyclic 1,2-dihydro-1,2-phosphasiletes are shown to be the
      thermodynamically preferred product, in contrast to the isomerization of the
      hydrocarbons, which favors the 1,3-butadiene structure. Furthermore, an
      unprecedented direct isomerization pathway to the 1,2-dihydro-1,2-phosphasiletes
      was identified. This pathway is competitive with the isomerization via the open
      chain butadienes and becomes favorable when electron-donating substituents are
      present on silicon. Figure 2-Phospha-4-silabicyclo[1.1.0]butane can isomerize
      directly into the more stable P,Si-cyclobutene via an unprecedented
      [sigma2s+sigma2a] process, which becomes favorable over the isomerization via the
      P,Si-butadiene when electron-donating substituents are present on silicon.

PMID- 16642337
TI  - Development of nuclear gene-derived molecular markers linked to legume genetic
      maps.
AB  - The systematic identification of the orthologous features of related organisms
      greatly facilitates comparative genomics, including research on genome evolution
      and comparative genetic mapping. In this study, we selected 274 unique gene
      sequences for the development of PCR-based genetic markers across fifteen legume
      genomes, representing six crop or model legume species from the phaseoloid and
      inverted repeat loss clades (IRLC). DNA sequence analysis demonstrated that 129
      of the amplified fragments represented single copy loci across most target
      diploid genomes. The majority of these markers are intron-spanning (70.5%) and
      linked to legume genetic maps (85.3%). The markers were grouped into four main
      categories: (1) intron-spanning relatively conserved, (2) intron-spanning
      diverged, (3) exon-derived conserved, and (4) exon-derived diverged. The extent
      of sequence divergence within each category indicates that the corresponding
      markers may have utility for assessing phylogenetic relationships at different,
      but overlapping, taxonomic levels. We tested marker performance on genomes that
      had not been previously sampled, representing 95 different species that span the
      diversity of the Fabaceae. Phylogenetic analyses support the orthology of
      amplified sequences, with the notable exception of an ambiguous affiliation of
      Lotus relative to the IRLC and phaseoloid clades.

PMID- 16642338
TI  - [Circularly arrayed peripheral spots on the iris].

PMID- 16642339
TI  - [Suddenly occurring exotropia with nystagmus in a 5-year-old girl].

PMID- 16642341
TI  - [A 16-year-old patient with dysphagia].
AB  - A 16-year-old man with an 8-year history of progressive dysphagia was referred to
      hospital. There was no specific finding in his family history. Physical
      examination was unremarkable. Complete blood count, serum electrolytes, and liver
      and kidney function tests were normal. Barium swallow revealed an extrinsic
      impression of the upper esophagus posteriorly. Magnetic resonance angiography
      demonstrated an aberrant origin of the right subclavian artery, leaving the aorta
      below the left subclavian artery. The artery had a retroesophageal course,
      causing the esophageal narrowing. Due to the persistence and worsening of the
      patient's symptoms, resection and reconstructive bypass surgery were recommended.
      Surgical correction was performed through a combined right supraclavicular
      incision and left posterolateral thoracotomy. After application of a vascular
      clamp, the aberrant right subclavian artery was ligated almost at its origin, and
      an end-to-side anastomosis was made with the right common carotid artery. At the
      end of the operative procedure, good pulses were palpated in the right radial
      artery. Postoperatively, the patient tolerated a regular diet without symptoms of
      dysphagia and was discharged on postoperative day 7.

PMID- 16642344
TI  - Hibernoma--correlation of histopathology and magnetic-resonance-imaging features
      in 10 cases.
AB  - OBJECTIVE, DESIGN AND PATIENTS: Hibernoma is an uncommon, slow-growing, benign
      soft-tissue tumour resembling brown adipose tissue. The histological appearances
      are well-documented, but there are relatively few descriptions of the magnetic
      resonance (MR) imaging features. We report a retrospective comparison of the
      histological and MR appearances of ten hibernomas of the extremities, classified
      histologically into lipoma-like [<70% multivacuolated adipocytes (MVAs)] and non
      lipoma-like hibernomas (>70% MVAs). RESULTS: The lipoma-like hibernomas measured
      4-27 cm in maximum size. All were well-defined on MR imaging and histology except
      for one subcutaneous lesion that blended in with surrounding fat histologically.
      All lesions were isointense with subcutaneous fat on T1- and T2-weighting apart
      from one lesion that was predominantly slightly hypointense on T1-weighting and
      predominantly slightly hyperintense on T2-weighting and STIR. Two slightly
      inhomogeneous lesions contained thin (<5 mm thickness) tortuous vessels. One
      patient received intravenous contrast, but the lesion did not enhance. The six
      non-lipoma-like hibernomas measured 2.5-15.5 cm in maximum size and all were
      unencapsulated. Three were well-defined and three partly ill-defined on MR
      imaging. There were no significant differences in the MR characteristics of the
      non-lipoma-like variants. On T1-weighting, the non-lipoma-like hibernomas that
      contained >90% MVAs were predominantly slightly hypointense to subcutaneous fat.
      One lesion was isointense with subcutaneous fat, but this lesion only contained
      from 80-90% MVAs. All non-lipoma-like lesions were slightly hyperintense on STIR
      but so too were two of the four lipoma-like lesions. Four of the six non-lipoma
      like lesions showed marked or moderate inhomogeneity due to thick septa and
      prominent vessels. Of the two cases that received intravenous contrast, both
      showed enhancement corresponding to regions of >90% MVAs or prominent vessels
      within fibrous septa. CONCLUSIONS: MR imaging has shown some distinguishing
      features between lipoma-like and non-lipoma-like hibernomas. Lipoma-like
      hibernomas are usually isointense with subcutaneous fat on T1-weighting, are
      either homogeneous or slightly inhomogeneous and may contain thin tortuous
      vascular structures. Non-lipoma-like hibernomas are pre-dominantly slightly
      hypointense to subcutaneous fat on T1-weighting, often display marked or moderate
      inhomogeneity with prominent septa and vessels and enhancement is typical. The
      appearances of non-lipoma-like hibernomas are not diagnostic and may be mimicked
      by lipoma variants and by well-differentiated liposarcoma or atypical lipoma.

PMID- 16642345
TI  - Evidence-based practice in the utilization of knee radiographs--a survey of all
      members of the British Orthopaedic Association.
AB  - There has been a debate amongst orthopaedic surgeons about which plain
      radiographs are required in common knee conditions and this is a 5-year review
      assessing the influence of recent publications on the use of radiographs. A
      postal survey of all members of the British Orthopaedic Association was
      performed. The response rate was 60% (990/1,650). There was a broad agreement on
      the use of anteroposterior and lateral radiographs. The use of the
      posteroanterior (PA) weight-bearing radiograph has increased from 82 to 86%. The
      use of skyline view for suspected arthritis and after knee replacement has
      increased from 23 to 41%. There is still disparity amongst orthopaedic surgeons
      regarding the knee flexion angle for skyline and weight-bearing views. After
      review of the literature we recommend that a single skyline view in 30 degrees
      flexion is adequate and should be a standard investigation in knee disorders. We
      also stress the importance of weight-bearing PA radiograph in 30 degrees knee
      flexion for adequate assessment in all patients with suspected arthritis.

PMID- 16642346
TI  - What is a nice smile like that doing in a place like this? Automatic affective
      responses to environments influence the recognition of facial expressions.
AB  - An affective priming paradigm with pictures of environmental scenes and facial
      expressions as primes and targets, respectively, was employed in order to
      investigate the role of natural (e.g., vegetation) and built elements (e.g.,
      buildings) in eliciting rapid affective responses. In Experiment 1, images of
      environmental scenes were digitally manipulated to make continua of priming
      pictures with a gradual increase of natural elements (and a decrease of built
      elements). The primes were followed by presentations of facial expressions of
      happiness and disgust as to-be-recognized target stimuli. The recognition times
      of happy faces decreased and the recognition times of disgusted faces increased
      as the quantity of natural/built material present in the primes
      increased/decreased. The physical changes also influenced the evaluated
      restorativeness and affective valence of the primes. In Experiment 2, the primes
      used in Experiment 1 were manipulated in such a way that they were void of any
      recognizable natural or built elements but contained either similar colours or
      similar shapes as primes in Experiment 1. This time the results showed no effect
      of priming. These results were interpreted to give support for a view that the
      priming effect by environmental pictures is due to the primes representing
      environmental scenes and not due to the presence of certain low-level colour or
      shape information in the primes. In all, the present results provide evidence
      that perception of environmental scenes elicits automatic affective responses and
      influences recognition of facial expressions.

PMID- 16642347
TI  - Masking visual stimuli by transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) applied over the occipital pole can
      suppress visual perception. Since its first description in 1989 by Amassian et
      al., this technique has widely been used to investigate visual processing at the
      cortical level. This article presents a review of experiments masking visual
      stimuli by TMS. The psychophysical characterization of TMS masking, the
      dependence on stimulus onset asynchrony between visual stimulus and TMS pulse,
      and the topography of masking within the visual field are considered. The
      relation between visual masking and the generation of phosphenes is discussed as
      well as the underlying physiological mechanisms.

PMID- 16642348
TI  - Different effects of the two types of spatial pre-cueing: what precisely is
      "attention" in Di Lollo's and Enns' substitution masking theory?
AB  - Enns and Di Lollo [Psychological Science, 8 (2), 135-139, 1997] have introduced
      the object substitution theory of visual masking. Object substitution masking
      occurs when focusing attention on the target is delayed. However, Posner
      (Quarterly Journal of Experimental Psychology, 32, 3-25, 1980) has already shown
      that attention can be directed to a target at least in two ways: intentionally
      (endogenously) and automatically (exogenously). We conducted two experiments to
      explore the effects of endogenous and exogenous cues on substitution masking. The
      results showed that when attention was shifted to the target location
      automatically (using a local peripheral pre-cue), masking was attenuated. A
      decrease in target identification dependent on a delay of mask offset, typical to
      substitution masking, was not observed. However, strong substitution masking
      occurred when the target location was not pre-cued or when attention was directed
      to the target location intentionally (using a symbolic pre-cue displayed
      centrally). The hypothesis of two different mechanisms of attentional control in
      substitution masking was confirmed.

PMID- 16642349
TI  - A comparison of frozen/thawed and fresh food substrates in development of
      Calliphora augur (Diptera: Calliphoridae) larvae.
AB  - While research has examined the effect of freezing and subsequent thawing on the
      decomposition of carcasses, no studies have investigated the effect of the
      freezing and thawing of tissues used as a developmental substrate by fly larvae.
      This paper reports on the results of such a study using larvae of Calliphora
      augur (Fabricius) on sheep's liver. Approximately 20 first-instar larvae were
      collected on sheep liver and subsequently transferred to paired treatments of
      fresh and frozen/thawed liver equilibrated to room temperature. They were then
      left undisturbed for 1-10 days. When the allocated time had elapsed, the body
      length of the larvae in each pair of groups was compared. No significant
      differences were detected between any pairs at a 1% level and only one pair was
      significantly different at a 5% level. We conclude that freezing and thawing of a
      developmental medium of sheep's liver has no significant effect on growth of C.
      augur larvae.

PMID- 16642350
TI  - Sudden death due to giant cell coronary arteritis.
AB  - An 89-year-old woman was found dead lying in her bed. Autopsy demonstrated a
      pronounced thickening of all coronary arteries except for the first 2-4 cm. Death
      was due to a recent myocardial infarction. Microscopically, the coronary arteries
      showed a substantial concentric thickening of all three layers with 90%
      narrowing. There was a dense transmural inflammatory infiltration with
      lymphocytes, macrophages, and numerous multinucleated giant cells. The CD68
      positive giant cells were mostly located at the media-intima border in the
      vicinity of fragmented fibers of the lamina elastica interna. The aorta and its
      major branches including the carotid arteries, however, were free of inflammation
      and thickening. The findings were characteristic for giant cell arteritis, the
      equivalent of temporal Horton arteritis, but isolated involvement of the coronary
      arteries is exceptional.

PMID- 16642351
TI  - Evaluation of an extended set of 15 candidate STR loci for paternity and kinship
      analysis in an Austrian population sample.
AB  - We investigated 15 polymorphic short tandem repeat (STR) loci (D1S1656, D7S1517,
      D8S306, D8S639, D9S304, D10S2325, D11S488, D12S391, D14S608, D16S3253, D17S976,
      D18S1270, D19S253, D20S161, and D21S1437) which are not included in the standard
      sets of forensic loci. The markers were selected according to the complexity of
      the polymorphic region: Of the 15 investigated loci, 7 loci showed a simple
      repeat structure (D9S304, D10S2325, D14S608, D16S3253, D18S1270, D19S253, and
      D21S1437), 3 loci (D7S1517, D12S391, and D20S161) consisted of compound repeat
      units, and 5 loci (D1S1656, D8S306, D8S639, D11S488, and D17S976) showed a more
      complex polymorphic region partly including different repeat blocks and
      incomplete repeat units, which resulted in a relatively high proportion of
      intermediate alleles. A population study on a sample of 270 unrelated persons
      from Austria was carried out. We did not observe significant deviations from
      Hardy-Weinberg expectations. The combined probability of exclusion for the 15
      loci was 0.99999998. In combination with the conventional set of STR markers
      included in commercially available kits (no linkage was observed between these 15
      loci and the Powerplex 16 System loci), these markers are approved as highly
      discriminating forensic tools, also suitable for the analysis of difficult
      paternity and kinship constellations.

PMID- 16642355
TI  - Noradrenergic modulation of working memory and emotional memory in humans.
AB  - RATIONALE: Noradrenaline (NA) is implicated in arousal. Working memory is
      dependent upon prefrontal cortex, and moderate levels of NA are thought to
      facilitate working memory whereas higher levels during extreme stress may impair
      working memory and engage more posterior cortical and sub-cortical circuitry. The
      NA system also influences emotional memory via modulation of the amygdalae and
      related mediotemporal structures. NA dysfunction and abnormalities in arousal
      dependent memory functions are evident in a variety of neuropsychiatric
      illnesses. OBJECTIVES: The authors provide a concise overview of pharmacological
      studies that have investigated effects of selective NA manipulations on working
      memory and emotional memory functions in healthy human volunteers. MATERIALS AND
      METHODS: Selection of relevant peer-reviewed publications was based on a PubMed
      search. RESULTS: Studies to date indicate that: (1) the beta-blocker propranolol
      impaired working and emotional memory, (2) clonidine frequently impaired working
      memory, and (3) reboxetine, a selective noradrenaline reuptake inhibitor,
      enhanced emotional memory for positive material. CONCLUSIONS: Improved
      understanding of coupling between NA, cortico-subcortical circuitry and human
      mnemonic functions will suggest novel therapeutic directions for the treatment of
      neuropsychiatric conditions, such as attention deficit hyperactivity disorder and
      post-traumatic stress disorder. Future research directions are discussed in
      relation to neuroimaging techniques, functional central nervous system
      polymorphisms and study designs.

PMID- 16642359
TI  - Capillary-assembled microchip as an on-line deproteinization device for capillary
      electrophoresis.
AB  - A capillary-assembled microchip (CAs-CHIP), prepared by simply embedding square
      capillaries in a lattice polydimethylsiloxane (PDMS) channel plate with the same
      channel dimensions as the outer dimensions of the square capillaries, has been
      used as a diffusion-based pretreatment attachment in capillary electrophoresis
      (CE). Because the CAs-CHIPs employ square-section channels, diffusion-based
      separation of small molecules from sample solutions containing proteins is
      possible by using the multilayer flow formed in the square section channel. When
      a solution containing high-molecular-weight and low-molecular-weight species
      makes contact with a buffer solution, the low-molecular-weight species, which
      have larger diffusion coefficients than the high-molecular-weight species, can be
      collected in a buffer-solution phase. The collected solution containing the low
      molecular-weight species is introduced into the separation capillary to be
      analyzed by CE. This type of system can be used for CE analysis in which
      pretreatment is required to remove proteins. In this work a fluorescently labeled
      protein and rhodamine-based molecules were chosen as model species and a
      feasibility study was performed.

PMID- 16642360
TI  - Bilateral epibulbar granulocytic sarcomas: a case of an 8-year-old girl with
      acute myeloid leukaemia.
AB  - PURPOSE: An 8-year-old girl with a history of acute myeloid leukaemia (AML)
      presented with bilateral ocular discomfort, conjunctival injection, photophobia,
      and epiphora. METHODS: Clinical examination and high-frequency ultrasound showed
      bilateral epibulbar tumours. RESULTS: Granulocytic sarcomas were suspected and
      leukaemic infiltration was confirmed by fine-needle aspiration biopsy based
      cytopathologic examination. CONCLUSIONS: Epibulbar granulocytic sarcoma in AML is
      rare (particularly in a child). We describe the first high-frequency ultrasound
      images and illustrate the use of a minimally invasive fine-needle aspiration
      biopsy technique to confirm our diagnosis.

PMID- 16642362
TI  - Precipitate inside the epithelial iris cyst: a report of two cases.
AB  - BACKGROUND: Epithelial iris cyst is a rare disease with various complications. To
      our knowledge, precipitate formation inside the cyst has never previously been
      described. The purpose of this report is to introduce this extremely atypical
      complication of epithelial iris cyst. METHODS: This case report presents two men
      out of 142 cases, aged 30 and 36, with epithelial iris cyst who developed
      precipitate level inside the lesions. The cyst fluid was drained and sent to the
      laboratory. Intracystic ethanol irrigation was performed as a treatment
      procedure. The patients were followed for 2 and 8 years. RESULTS: There was no
      inflammatory response outside the cysts. Both cysts contained lymphocytes and one
      included epithelial cells, but neither contained organisms. The cysts were
      treated successfully by intracystic ethanol irrigation. CONCLUSIONS: Intracystic
      precipitate formation is a rare manifestation of the epithelial iris cyst.

PMID- 16642363
TI  - Macular pigment optical density measurement in autofluorescence imaging:
      comparison of one- and two-wavelength methods.
AB  - BACKGROUND: Measurement of macular pigment (MP) can be performed by analysis of
      autofluorescence (AF) images. These can be obtained by standard 488-nm argon
      imaging alone (one wavelength, 1-Lambda) or with additional digital subtraction
      of a second image at 514 nm (two wavelengths, 2-Lambda). The analyses are easy to
      perform, and we present a comparison of both methods and investigate their
      reliability and repeatability. METHODS: Inter-individual variability of MP
      optical density (MPOD) measurements was assessed in single eyes of 120 subjects
      with a modified Heidelberg retina angiograph (HRA). MPOD values obtained with one
      (488 nm) Lambda (MPOD(1Lambda)) were compared with those obtained with two (488
      nm and 514 nm) Lambda (MPOD(2Lambda)). To test the repeatability of the two
      methods, 20 subjects were subjected to five repeated measurements. RESULTS: Among
      120 individuals, mean MPOD(1Lambda) at 0.5 degrees eccentricity was 0.59 (range
      0.06-1.32), mean MPOD(2Lambda) was 0.5 (range 0.01-1.21). Apart from this
      systematic difference, 1-Lambda and 2-Lambda measurements at 0.5 degrees agreed
      well across the range of MPOD values (beta=0.964, around the fovea, a systematic
      difference (0.11) was accompanied by declining agreement at higher MPOD values
      (beta=0.669, 95% CI 0.519-0.844; R=0.48). Among 20 subjects with five repeated
      measurements, the reliability ratio was 0.97 for 1-Lambda and 0.94 for 2-Lambda
      at 0.5 degrees and 0.93 and 0.94, respectively, at a distance of 2 degrees.
      CONCLUSIONS: Both methods showed a high repeatability with little influence of
      measurement error. They agree well at the fovea centre in terms of ranking
      individuals according to their MPOD, but provide increasingly deviating results
      at a distance of 2 degrees around the fovea, probably because the 1-Lambda
      method, in contrast to the 2-Lambda method, cannot compensate for disruptive
      influences and for heterogeneous distributions of the lipofuscin fluorophores.
      The 1-Lambda method can be performed by standard HRA and could therefore be used
      for screening in multicentre studies, but only approaches the actual amounts of
      MP. The 2-Lambda method remains the more precise method for MPOD measurement in
      autofluorescence imaging.

PMID- 16642364
TI  - Local and systemic effects on blood lactate concentration during exercise with
      small and large muscle groups.
AB  - To evaluate the relationship between lactate release and [lac](art) and to
      investigate the influence of the catecholamines on the lactate release, 14
      healthy men [age 25+/-3 (SE) year] were studied by superimposing cycle on forearm
      exercise, both at 65% of their maximal power reached in respective incremental
      tests. Handgrip exercise was performed for 30 min at 65% of peak power. In
      addition, between the tenth and the 22nd minute, cycling with the same intensity
      was superimposed. The increase in venous lactate concentration ([lac](ven))
      (rest: 1.3+/-0.4 mmol.l(-1); 3rd min: 3.9+/-0.8 mmol.l(-1)) begins with the
      forearm exercise, whereas arterial lactate concentration ([lac](art)) remains
      almost unchanged. Once cycling has been added to forearm exercise (COMB),
      [lac](art) increases with a concomitant increase in [lac](ven) (12th min:
      [lac](art), 3.2+/-1.3 mmol.l(-1); [lac](ven), 5.7+/-2.2 mmol.l(-1)). A
      correlation between oxygen tension (P(v)O(2)) and [lac](ven) cannot be detected.
      There is a significant correlation between [lac](art) and norepinephrine ([NE])
      (y=0.25x+1.2; r=0.815; p<0.01) but no correlation between lactate release and
      epinephrine ([EPI]) at moderate intensity. Our main conclusion is that lactate
      release from exercising muscles at moderate intensities is neither dependent on
      P(v)O(2) nor on [EPI] in the blood.

PMID- 16642365
TI  - Effects of intracellular pH and Ca2+ on the activity of stretch-sensitive cation
      channels in leech neurons.
AB  - The effects of intracellular pH and calcium on the activity of the leech
      mechanosensitive cation channels have been studied. These channels exhibited two
      activity modes denoted as spike-like (SL) and multiconductance (MC). In the
      absence of mechanical stimulation, acidification of the intracellular side of
      membrane patches from 7.2 to 6.2 reversibly increased the mean channel open time
      as well as the opening frequency in the SL mode. Channels in MC mode were
      activated by a pH(i) reduction from 7.2 to 6.2, but were inhibited at pH(i) 5.5.
      Unlike MC mode, SL mode was strongly activated by intracellular Ca(2+). Fura-2
      imaging experiments showed that intracellular calcium was induced to increase by
      hypotonic cell swelling. The major component of this response did not require
      extracellular calcium. A component of the swelling-induced calcium response was
      sensitive to blockers of stretch-sensitive cation channels. The results indicate
      that the two activity modes of mechanosensitive channels of leech neurons respond
      differently to changes of intracellular pH and calcium. The sensitivity of the
      channel to micromolar concentrations of internal free calcium, along with its
      permeability to this ion, is consistent with a role in the amplification of
      mechanically induced Ca(2+) signals in leech neurons.

PMID- 16642367
TI  - Cytomegalovirus esophagitis in a child with human immunodeficiency virus-1
      infection presenting as fever of unknown origin and stunted growth.
AB  - We report a 12-year old boy with human immunodeficiency virus-1 infection and
      cytomegalovirus-associated esophagitis, who presented with an indolent clinical
      course associated with fever of an unknown origin, failure to thrive and weight
      loss.

PMID- 16642368
TI  - A novel mutation in the MSX2 homeobox gene of a family with foramina parietalia
      permagna, headache and vascular anomaly.

PMID- 16642369
TI  - Aortoesophageal fistula due to double aortic arch and prolonged nasogastric
      intubation: case report and review of the literature.
AB  - BACKGROUND: The authors present a patient and describe other cases from the
      literature which demonstrate that prolonged use of nasogastric tubes can result
      in life-threatening aortoesophageal fistula formation in patients with a double
      aortic arch. CONCLUSION: Aortoesophageal fistula (AEF) is an abnormal
      communication between the esophagus and the aorta. It can cause massive
      gastrointestinal hemorrhage. We present an infant with an operatively corrected
      double aortic arch, who developed this complication after prolonged nasogastric
      intubation.

PMID- 16642370
TI  - Evidence for autosomal dominant inheritance in prenatally diagnosed CHAOS.
AB  - Congenital high airway obstruction syndrome (CHAOS) is a rare prenatal diagnosis
      consisting of a typical fetal triad of large hyperechogenic lungs, flattened or
      inverted diaphragms and ascites. Most cases are sporadic with unknown incidence.
      Before attempts of fetoscopic fetal salvage or ex utero intrapartum treatment
      (EXIT) are considered, additional malformations must be carefully excluded as
      CHAOS may be part of various monogenic conditions or chromosomal disorders. We
      report an unique family with autosomal dominant inheritance of CHAOS and variable
      expression in the affected father and two affected children. It is concluded that
      minor expression in one of the parents may be an important indicator for genetic
      counseling in CHAOS and management of future pregnancies.

PMID- 16642372
TI  - Immunogold-labeled S-phase neoblasts, total neoblast number, their distribution,
      and evidence for arrested neoblasts in Macrostomum lignano (Platyhelminthes,
      Rhabditophora).
AB  - Neoblasts in Platyhelminthes are the only cells to proliferate and differentiate
      into all cell types. In Macrostomum lignano, the incorporation of 5'-bromo-2'
      deoxyuridine (BrdU) in neoblasts confirmed the distribution of S-phase cells in
      two lateral bands. BrdU labeling for light and for transmission electron
      microscopy (TEM) identified three populations of proliferating cells: somatic
      neoblasts located between the epidermis and gastrodermis (mesodermal neoblasts),
      neoblasts located within the gastrodermis (gastrodermal neoblasts), and gonadal S
      phase cells. In adults, three stages of mesodermal neoblasts (2, 2-3, and 3)
      defined by their ultrastructure were found. Stage 1 neoblasts where only seen in
      hatchlings. These stages either were phases within the S-phase of one neoblast
      pool or were subsequent stages of differentiating neoblasts, each with its own
      cell cycle. Regular TEM and immunogold labeling provided the basis for
      calculating the total number of neoblasts and the ratio of labeled to non-labeled
      neoblasts. Somatic neoblasts represented 6.5% of the total number of cells. Of
      these, 27% were labeled in S-phase. Of this fraction, 33% were in stage 2, 46% in
      stage 2-3, and 21% in stage 3. Immunogold labeling substantiated results
      concerning the differentiation of neoblasts into somatic cells. Non-labeled stage
      2 neoblasts were present, even after a 2-week BrdU exposure. Double labeling of
      mitoses and FMRF-amide revealed a close spatial relationship of mesodermal
      neoblasts with the nervous system. Immunogold-labeled sections showed that nearly
      70% of S-phase cells were in direct contact or within 5 microm from nerve cords.

PMID- 16642373
TI  - Distribution and change in number of gonadotropin-releasing hormone-1 neurons
      following activation of the photoneuroendocrine system in the chick, Gallus
      gallus.
AB  - The photoneuroendocrine system (PNES) of chicks was activated by transferring
      birds to a long photoperiod and by giving them a diet supplemented with
      sulfamethazine (SMZ), a compound that augments the effect of long-day
      photostimulation. We wished to determine (1) the number of gonadotropin-releasing
      hormone-1 (GnRH-1) neurons in each identified nucleus (n.) in the subpallium and
      diencephalon and the major terminal fields (TFs) of GnRH-1 neurons, and (2) the
      effect of SMZ on the immunoreactive expression of GnRH-1 in perikarya. Four
      groups of birds were exposed to one of two light treatments, viz., light:dark
      (LD) cycles of LD20:4 or LD8:16, and given one of two rations, viz., control or
      one supplemented with SMZ (n=5/treatment). After 3 days, chicks were
      anesthetized, and their brains were prepared for immunocytochemistry with an
      antibody identifying GnRH-1 neurons. Seven areas or nuclei contained GnRH-1
      neurons: paramedial septal n., preoptic periventricular n./periventricular
      hypothalamic n., bed n. of the pallial commissure (NCPa), parvocellular lateral
      and medial septal n., lateral septum near the ventral horn of the lateral
      ventricle, parvocellular lateral anterior thalamic n., and displaced thalamic
      neurons. Six TFs of GnRH neurons were found including the organum vasculosum of
      lamina terminalis (OVLT), preoptic recess (POR), hypothalamic recess (HR),
      lateral septum adjacent to the ventral horn of the lateral ventricle (SL-VLvh)
      associated with the choroid plexus, subseptal organ (SSO), and external zone of
      the median eminence. The extensive TFs for GnRH-1 neurons in the OVLT, POR/HR, SL
      VLvh, and SSO suggested that a large amount of the peptide was secreted into the
      ventricular system. The NCPa responded to the photoperiod and SMZ treatments
      combined, with a significant increase in GnRH-1 cell number compared with birds
      fed control diets and exposed to a short-day photoperiod. More than 73% of GnRH-1
      neurons resided in the septal region of the subpallium and not in the preoptic
      hypothalamic region characteristic of several mammalian species. Thus, instead of
      the traditional descriptor hypothalamo-pituitary-gonadal axis, either the septal-
      or subpallial-pituitary-gonadal axis may be more appropriate for describing the
      neuroendocrine axis related to gonadal function in birds.

PMID- 16642371
TI  - A phase I clinical and pharmacokinetic study of the multi-drug resistance protein
      1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with
      advanced cancer.
AB  - PURPOSE: Multi-drug resistance mediated by ATP-binding cassette trans-membrane
      protein pumps is an important cause of cancer treatment failure. Sulindac has
      been shown to be a competitive substrate for the clinically important resistance
      protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti
      cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines.
      METHODS: We conducted a dose-escalating, single arm, prospective, open label, non
      randomised phase I trial of epirubicin (75 mg/m(2)) in combination with
      escalating oral doses of sulindac (0-800 mg) in patients with advanced cancer to
      identify an appropriate dose of sulindac to use in future resistance studies.
      Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3.
      RESULTS: Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1
      ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy)
      were enrolled. Eight patients received a full six cycles of treatment; 14
      patients received three or more cycles. Dose-limiting toxicity was observed in
      two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a
      patient with advanced lung cancer), and sulindac 600 mg was deemed to be the
      maximum tolerated dose. Sulindac had no effect on epirubicin pharmacokinetics.
      Among 15 patients with evaluable tumour, two partial responses were seen
      (malignant melanoma and breast cancer). Four others had prolonged stable disease.
      CONCLUSION: Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses
      for phase II studies for these agents in combination.

PMID- 16642380
TI  - [Transgluteal mini-incision. Technique and our own results].
AB  - BACKGROUND: A transgluteal mini-incision technique according to the approach of
      Bauer et al. is described. MATERIAL AND METHODS: Altogether 194 patients were
      supplied with a cementless primary total hip endoprosthesis using this approach.
      Our own results regarding ASA, body mass index, operation time, transfusions, the
      course of the Hb values, and the use of drugs against pain are described.
      RESULTS: The approach does not show any dependence on ASA and BMI. Operation
      time, blood loss, and use of drugs against pain are not influenced by it. Angled
      reamers and impactors are mandatory to prevent additional damage of soft tissue.
      The cosmetic benefit seems to be the only advantage. The approach cannot be
      recommended for general use.

PMID- 16642382
TI  - Overexpression of carnation S-adenosylmethionine decarboxylase gene generates a
      broad-spectrum tolerance to abiotic stresses in transgenic tobacco plants.
AB  - Polyamines (PAs), such as putrescine, spermidine, and spermine, are present in
      all living organism and implicate in a wide range of cellular physiological
      processes. We have used transgenic technology in an attempt to evaluate their
      potential for mitigating the adverse effects of several abiotic stresses in
      plants. Sense construct of full-length cDNA for S-adenosylmethionine
      decarboxylase (SAMDC), a key enzyme in PA biosynthesis, from carnation (Dianthus
      caryophyllus L.) flower was introduced into tobacco (Nicotiana tabacum L.) by
      Agrobacterium tumefaciens-mediated transformation. Several transgenic lines
      overexpressing SAMDC gene under the control of cauliflower mosaic virus 35S
      promoter accumulated soluble total PAs by 2.2 (S16-S-4) to 3.1 (S16-S-1) times
      than wild-type plants. The transgenic tobacco did not show any difference in
      organ phenotype compared to the wild-type. The number and weight of seeds
      increased, and net photosynthetic rate also increased in transgenic plants.
      Stress-induced damage was attenuated in these transgenic plants, in the symptom
      of visible yellowing and chlorophyll degradation after all experienced stresses
      such as salt stress, cold stress, acidic stress, and abscisic acid treatment.
      H2O2-induced damage was attenuated by spermidine treatment. Transcripts for
      antioxidant enzymes (ascorbate peroxidase, manganase superoxide dismutase, and
      glutathione S-transferase) in transgenic plants and GUS activity transformed with
      SAMDC promoter::GUS fusion were induced more significantly by stress treatment,
      compared to control. These results that the transgenic plants with sense SAMDC
      cDNA are more tolerant to abiotic stresses than wild-type plants suggest that PAs
      may play an important role in contributing stress tolerance in plants.

PMID- 16642383
TI  - The sensilla of Aedes and Anopheles mosquitoes and their importance in
      repellency.
AB  - The aim of this study was to detect the role of some mosquito organs in their
      sensation of repellent materials. A total of 250 females (15 days old) of the
      target species Aedes aegypti and Anopheles stephensi were prepared and divided
      into five groups: group 1, without antenna; group 2, without maxillary bulbs;
      group 3, without proboscis; group 4, without frontal tarsus; and group 5, normal
      females as control. A mixture of five oils containing Litsea cubeba 1%, Melaleuca
      leucadendron 1%, Melaleuca quinquenervia 1%, Viola odorata 1%, and Nepeta cataria
      1% was included in a complex solvent containing 20% genapol, 10% polyethylene
      glycol, 20% ethanol, and 50% water. Furthermore, Bayrepel was used in this
      experiment at a 20% concentration in the same solvent. Pure water was used as
      control in this study. The test was carried out by spreading 100 microl of the
      repellent material or water on a 30-cm2 exposure area of a human volunteer's arm.
      In A. aegypti, the biting and landing percentages increased significantly in
      those mosquito groups that lacked some organs (especially maxillary bulbs), while
      in A. stephensi, it became not clear which organ is responsible for perception of
      repellents.

PMID- 16642384
TI  - Repellency effect of forty-one essential oils against Aedes, Anopheles, and Culex
      mosquitoes.
AB  - Since ancient times, plant products were used in various aspects. However, their
      use against pests decreased when chemical products became developed. Recently,
      concerns increased with respect to public health and environmental security
      requiring detection of natural products that may be used against insect pests. In
      this study, 41 plant extracts and 11 oil mixtures were evaluated against the
      yellow fever mosquito, Aedes aegypti (Linnaeus), the malaria vector, Anopheles
      stephensi (Liston), and the filariasis and encephalitis vector, Culex
      quinquefasciatus (Say) (Diptera: Culicidae) using the skin of human volunteers to
      find out the protection time and repellency. The five most effective oils were
      those of Litsea (Litsea cubeba), Cajeput (Melaleuca leucadendron), Niaouli
      (Melaleuca quinquenervia), Violet (Viola odorata), and Catnip (Nepeta cataria),
      which induced a protection time of 8 h at the maximum and a 100% repellency
      against all three species. This effect needs, however, a peculiar formulation to
      fix them on the human skin.

PMID- 16642385
TI  - Persistency of larvicidal effects of plant oil extracts under different storage
      conditions.
AB  - The persistency of larvicidal effects of 13 oils (camphor, thyme, amyris, lemon,
      cedarwood, frankincense, dill, myrtle, juniper, black pepper, verbena,
      helichrysum, and sandalwood) was examined by storage of 50-ppm solutions under
      different conditions (open, closed, in the light, and in the dark) for 1 month
      after the preparation of the solutions. The stored solutions were tested against
      Aedes aegypti larvae for four times during the storage period. Some oils under
      some conditions stayed effective until the last test, while some solutions had
      lost their toxicity during a short time after preparation. Thus, the mode of
      storage is absolutely important for the larvicidal effects. The fresh
      preparations were always the best.

PMID- 16642386
TI  - Larvicidal effects of various essential oils against Aedes, Anopheles, and Culex
      larvae (Diptera, Culicidae).
AB  - Mosquitoes in the larval stage are attractive targets for pesticides because
      mosquitoes breed in water, and thus, it is easy to deal with them in this
      habitat. The use of conventional pesticides in the water sources, however,
      introduces many risks to people and/or the environment. Natural pesticides,
      especially those derived from plants, are more promising in this aspect. Aromatic
      plants and their essential oils are very important sources of many compounds that
      are used in different respects. In this study, the oils of 41 plants were
      evaluated for their effects against third-instar larvae of Aedes aegypti,
      Anopheles stephensi and Culex quinquefasciatus. At first, the oils were surveyed
      against A. aegypti using a 50-ppm solution. Thirteen oils from 41 plants
      (camphor, thyme, amyris, lemon, cedarwood, frankincense, dill, myrtle, juniper,
      black pepper, verbena, helichrysum and sandalwood) induced 100% mortality after
      24 h, or even after shorter periods. The best oils were tested against third
      instar larvae of the three mosquito species in concentrations of 1, 10, 50, 100
      and 500 ppm. The lethal concentration 50 values of these oils ranged between 1
      and 101.3 ppm against A. aegypti, between 9.7 and 101.4 ppm for A. stephensi and
      between 1 and 50.2 ppm for C. quinquefasciatus.

PMID- 16642388
TI  - Stimulation of osteoclast formation by inflammatory synovial fluid.
AB  - Peri-articular bone resorption is a feature of arthritis due to crystal
      deposition and rheumatoid disease. Under these conditions, the synovial fluid
      contains numerous inflammatory cells that produce cytokines and growth factors
      which promote osteoclast formation. The aim of this study was to determine
      whether inflammatory synovial fluid stimulates the formation of osteoclasts.
      Synovial fluid from rheumatoid arthritis (RA), pyrophosphate arthropathy (PPA)
      and osteoarthritis (OA) patients was added to cultures (n=8) of human peripheral
      blood mononuclear cells (PBMCs) in the presence and absence of macrophage colony
      stimulating factor (M-CSF) and the receptor activator of NF-kappaB ligand
      (RANKL). Osteoclast formation was assessed by the formation of cells positive for
      tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and the
      extent of lacunar resorption. The addition of 10% OA, RA and PPA synovial fluid
      to PBMC cultures resulted in the formation of numerous multinucleated or
      mononuclear TRAP(+) and VNR(+) cells which were capable of lacunar resorption. In
      contrast to PBMC cultures incubated with OA synovial fluid, there was marked
      stimulation of osteoclast formation and resorption in cultures containing
      inflammatory RA and PPA synovial fluid which contained high levels of tumour
      necrosis factor alpha, a factor which is known to stimulate RANKL-induced
      osteoclast formation.

PMID- 16642391
TI  - Mutans streptococci and lactobacilli in plaque on a leucite-reinforced dental
      ceramic and on a calcium aluminate cement.
AB  - In this in vivo study, the proportions of mutans streptococci and lactobacilli in
      plaque were examined (1) on proximal surfaces of bonded, leucite-reinforced
      ceramic crowns and (2) on class V restorations of calcium aluminate cement (CAC).
      The examined proportions were intraindividually compared with those of resin
      composite and enamel. Mutans streptococci and lactobacilli in samples from plaque
      that was accumulated for 10 days on the following surfaces were determined by
      cultivation on blood agar plates and species-selective plates: (1) proximal
      leucite-reinforced ceramic crown, class II composite and enamel (n=11); and (2)
      class V restoration of CAC and composite, and enamel (n=17). Mutans streptococci
      and lactobacilli in the samples were distributed in three groups: 0, >0-1, and
      >1% of total bacteria. The surfaces with detected mutans streptococci were
      similarly distributed between the materials and enamel. The highest proportion of
      mutans streptococci and lactobacilli were observed on ceramic followed by
      composite and enamel. A higher proportion of lactobacilli, but not of mutans
      streptococci, was detected on enamel compared to CAC and composite. However, no
      significant differences were found between the surfaces. Conclusively, the
      materials investigated did not show different relative proportions of mutans
      streptococci and lactobacilli in plaque, compared to enamel.

PMID- 16642392
TI  - [Renal oncocytoma with metastasis from breast carcinoma: a contribution to the
      differential diagnosis of tumourous lesions of the kidney].
AB  - The case of a renal oncocytoma involvement by metastasis from breast carcinoma in
      a 83-year-old woman is reported. The literature of tumour-into-tumour metastasis
      is reviewed. In conclusion, metastasis of breast carcinoma to a benign renal
      tumour is very rare.

PMID- 16642399
TI  - Secretory products of breast cancer cells upregulate hyaluronan production in a
      human osteoblast cell line.
AB  - Hyaluronan (HA) has been implicated in breast cancer progression and metastasis
      to lymph nodes. Although breast cancer has a strong propensity for metastasis to
      the bone, the role of HA in the development of bone metastasis in breast cancer
      is not well delineated. In order to determine the role of HA in breast cancer
      induced osteolysis, we examined the effect of secretory products in the
      conditioned medium of breast cancer cell lines on the expression of hyaluronan
      synthases (HAS), accumulation of HA in pericellular matrix, secretion of HA in
      the culture media, and on expression of surface HA receptors, in a human immature
      osteoblast cell line (Hfob). Our results show that conditioned medium derived
      from breast cancer cells upregulate the expression of hyaluronan synthases, HAS1
      and HAS2, followed by significant increase in pericellular and secreted HA in
      Hfob cells. Our results further demonstrate that both CD44 and receptor for
      hyaluronan-mediated motility (RHAMM) are involved in binding cell surface
      associated HA on Hfob cells. Analysis of the growth factors in the conditioned
      medium implicates TGF-beta1 in the modulation of HAS1 and HAS2, as well as in the
      increase in pericellular and secreted HA. This report is the first to show that
      soluble factors produced by breast cancer cells mediate increase in HA production
      in osteoblasts.

PMID- 16642400
TI  - The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells
      depends on the relative degree of invasive and metastatic potential.
AB  - Breast cancer has a predilection for metastasis to the bone marrow. The
      preprotachykinin-I (PPT-I) gene has a central role in the early migration of
      breast cancer cells into the bone marrow, making this organ a latent repository
      of the cancer cells. This study investigated whether the invasive and metastatic
      potential of breast cancer cells correlate with the expression of the PPT-I gene
      and the receptors for its peptides, neurokinin-1 (NK-1) and NK-2. The studies
      compared cells that are non-tumorigenic (MCF12A), low metastatic and invasive
      potential (MCF7), and sublines of MCF with increased invasive and metastatic
      potential (LCC1 and LCC2). LCC2, but not LCC1 is tamoxifen resistant.
      Quantitative RT-PCR showed increased expression of PPT-I, NK-1 and NK-2 mRNA LCC1
      and LCC2. MCF7 required stimulation by phorbol ester for NK-1 induction. The
      levels of NK-2 mRNA were significantly increased in LCC2. Clonogenic assays with
      specific receptor antagonists showed a predominant role for NK-2 in the
      proliferation of both LCC1 and LCC2. While the growth rate of LCC1 and LCC2 were
      similar, the latter showed increased migration. Use of a nude mouse model
      confirmed higher metastatic potential of LCC2, including increased migration to
      regions of the endosteum. Overall, these studies show a correlation between three
      neuroendocrine-related genes: PPT-I, NK-1 and NK-2 and the metastatic potential
      of specific breast cancer cells. These cells provide a model for future studies
      on bone marrow metastasis.

PMID- 16642401
TI  - The current understanding of the molecular determinants of inflammatory breast
      cancer metastasis.
AB  - Inflammatory breast cancer is a highly aggressive and metastatic form of locally
      advanced breast cancer that carries a significantly worse prognosis than non
      inflammatory breast cancers. Unfortunately, the molecular basis of this deadly
      form of breast cancer has been understudied. Over the past 10 years new studies
      have begun to reveal a unique molecular profile of IBC shedding light on its
      unique ability to rapidly invade and metastasize via the dermal lymphatic system
      of the skin overlying the breast. The goal of this review is to introduce IBC to
      the reader and provide a brief overview of what is known about the metastatic
      mechanisms of the disease.

PMID- 16642402
TI  - New NMR assignment 1H, 13C, and 15N assignment of the second PH domain of human
      pleckstrin (234-350).

PMID- 16642403
TI  - 1H, 13C, and 15N backbone resonance assignments for PSE-4, a 29.5 kDa class A
      beta-lactamase from Pseudomonas aeruginosa.

PMID- 16642404
TI  - Anomalous origin of the three coronary arteries from the right aortic sinus
      Valsalva: role of MDCT coronary angiography.
AB  - BACKGROUND: Monocuspal origin of all three coronary arteries through separate
      ostia from the right aortic sinus (RCS) is a rare occurrence. To date, the use of
      multidetector computed tomography (MDCT) for imaging of congenitally abnormal
      coronary arteries has been discussed only in few individual case reports.
      OBJECTIVE: To describe the role of MDCT coronary angiography in the evaluation of
      two rare cases of monocuspal origin of all three coronary from RCS. PATIENTS AND
      METHODS: We had a retrospective review of clinical information and imaging
      studies for two patients presented with chest pain. Both patients underwent
      conventional coronary angiography followed by noninvasive imaging with MDCT.
      RESULTS: Both patients had anomalous origin of the all three coronary arteries
      from the RCS. In one case the LAD took an intramural course in between the aorta
      and the right ventricular outflow tract (RVOT) while it passed anterior to the
      RVOT in the other patient. In the first patient, there was also associated
      coronary fistula to the right ventricle along with right coronary artery (RCA)
      and left anterior descending coronary artery (LAD) narrowing. Both the stenosed
      segments were successfully stented and were demonstrated to be patent in the
      subsequent MDCT. CONCLUSION: Monocuspal origin of all three coronary artery from
      the RCS is a rare anomaly, can be reliably diagnosed by MDCT. CT angiogram is a
      convenient complementary tool for the coronary arteriography.

PMID- 16642405
TI  - Prognosis of polymyositis and dermatomyositis.

PMID- 16642406
TI  - Paraoxonase and arylesterase levels in rheumatoid arthritis.
AB  - It was reported that lipid peroxidation (LPO) products increase in rheumatoid
      arthritis (RA) patients and increased LPO products reduce many antioxidants.
      Lipid hydroperoxides (LOOHs) are byproduct of LPO. Paraoxonase (PON),
      arylesterase (ARE), free sulfhydryl (SH) groups, and ceruloplasmin (CP) are
      enzymes or proteins with antioxidant characteristics. This study aims to
      determine the levels of LOOHs and SH, and the activities of PON1, ARE, and CP in
      RA patients. The study included 47 active RA cases and 23 healthy volunteers. The
      levels of LOOHs and SH, and the activities of PON1, ARE, and CP were determined
      using appropriate methods. Student's t test and Spearman's correlation analysis
      methods were employed in the statistical evaluation. The level of LOOHs was found
      to be higher (p<0.001), while the level of SH and the activities of PON1, ARE,
      and CP were found to be lower (p<0.001, <0.001, <0.01, and <0.01, respectively)
      in the RA patient group when compared with the control group. There was a
      negative correlation between the level of LOOHs and the activity of PON1 in the
      patient group (r= -0.420 and p<0.01). The results of our study indicate increased
      oxidant and decreased antioxidant presence in RA patients. PON1 and ARE are known
      to have antiatherosclerotic effects in addition to their antioxidant
      characteristics. As the decrease in these antioxidants, resulting from increased
      oxidative stress in RA patients, development of atherosclerosis besides tissue
      injury seems inevitable.

PMID- 16642407
TI  - Extraspinal tuberculous arthritis in HIV era.
AB  - A worldwide reemergence of tuberculosis is appreciable. Extrapulmonary
      tuberculosis has been observed to increase disproportionately from past
      incidence. One of the main attributing factors is the human immunodeficiency
      virus (HIV) infection. The objective of this study was to study clinical
      features, laboratory findings, and association with HIV infection in patients
      with peripheral tuberculous arthritis. The retrospective study was performed by
      reviewing the medical records of 27 patients with extraspinal tuberculous
      arthritis treated from January 1994 to December 2002. The diagnosis was made
      either by compatible clinical presentation and positive culture for Mycobacterium
      tuberculosis or histological finding of caseating granuloma in biopsy tissue or
      both. The average age of the patients' population was 49.3 years (range 27-74
      years), made up of a 52% or 14 patients of male subjects. The mean duration of
      disease before seeking medical treatment was 10.2+11 weeks and from onset to
      diagnosis was 25 weeks. The most frequently affected joints were knees (36.6%)
      followed by wrists, ankles, shoulders, hips, sacroiliacs, and elbows,
      respectively. Monoarthritis was the main feature of this group, except for two
      patients who had two and three joints involvement, respectively. Dactylitis
      (tenosynovitis) was also found in two out of the 27 patients. Six patients (24%)
      had active pulmonary infiltration on chest X-ray. Of 11 patients with synovial
      polymerase chain reaction (PCR) testing for tuberculosis, seven patients had
      positive result. Only one patient with extraspinal tuberculous arthritis tested
      positive for HIV. Therefore, extraspinal tuberculous arthritis is observed to be
      usually present with chronic monoarthritis. The diagnosis is delayed in most
      occasions. PCR from synovial fluid may facilitate rapid diagnosis of tuberculous
      arthritis. Human immunodeficiency virus may not be a main contributing factor for
      extraspinal tuberculous arthritis.

PMID- 16642409
TI  - Effect of different flavonoids on collagen synthesis in human fibroblasts.
AB  - In this study, we discovered that flavonoids belonging to the subclasses:
      (flavanone, flavone, and flavonol) display differential effects on the synthesis
      of collagen in human dermal fibroblasts. At 80 microg/ml flavonoids quercetin
      3,3',4', 5,7-pentahydroxyflavone, 3-methyl quercetin, and 7-hydroxyflavone
      significantly decreased the total protein concentration which was a direct
      consequence of their cytotoxic effect, while naringenin exhibited no effect on
      total collagen and total protein concentration. Quercetin-3,3'4',7-tetramethyl
      ether, 4'-hydroxyflavanone, flavanone, and fisetin significantly decreased
      collagen concentration while morin, rutin, and chrysin increased collagen
      concentration without changing the overall protein concentration. The initial
      screening performed in this study enables the identification of compounds that
      exert significant effects on fibroblast function and show potential as starting
      material for pharmaceutical preparations targeted against various disorders
      centered around disturbed collagen metabolism.

PMID- 16642418
TI  - The impact of syringe deregulation on sources of syringes for injection drug
      users: preliminary findings.
AB  - In 2001, New York State enacted legislation to allow the provision of syringes by
      pharmacies and healthcare providers without prescription (ESAP, the Expanded
      Syringe Access Demonstration Program). A longitudinal study of IDUs (n=130) found
      that pre-ESAP, about half used only the safest source (needle exchange programs
      [NEPs]). Post-ESAP implementation, ESAP sources were initiated by 14%. Frequency
      of injection was related to ESAP use and those who used unsafe (or possibly
      unsafe) sources were as likely to use ESAP as those who had previously used only
      NEPs. The findings indicate that providing multiple sources of safe syringes for
      IDUs is necessary.

PMID- 16642419
TI  - Effectiveness of a screening program for hepatitis C.
AB  - We sought to determine the outcomes of a screening program for hepatitis C virus
      (HCV) infection. Of 536 veterans initially screened between July 2000 and June
      2001 for risk factors and then tested positive for antibody for HCV, only 260
      (48.5%) kept their initial appointments for further evaluation; 51 were not
      viremic and only 19 (9.1%) were treatment eligible. Of the 276 who did not keep
      their initial appointments, 92 were subsequently evaluated over the next 2 years
      and 23 (25%) were treatment eligible, along with another 15 from the first group.
      Thus, with appropriate intervention and long-term follow-up, there were 57
      treatment candidates. In conclusion, most veterans who tested positive either
      failed to keep their appointment or were ineligible for treatment when first
      evaluated. Over the following 2 years, some were lost to follow-up, many
      continued to have contraindication(s) to antiviral therapy, and relatively few
      were treatment candidates.

PMID- 16642420
TI  - Anal tumor diagnosed after the recovery of Fournier gangrene.

PMID- 16642421
TI  - Randomized active and placebo-controlled endoscopy study of a novel protected
      formulation of oral alendronate.
AB  - Although generally well tolerated, oral aminobisphosphonates have been associated
      with sporadic cases of severe esophageal injury attributed to pill contact. A
      novel protected formulation of oral alendronate uses an inert cylindrical shell
      to prevent mucosal contact with intact tablets. An active and placebo-controlled
      endoscopy study was undertaken to assess mucosal injury associated with this
      protected formulation. Healthy volunteers with normal baseline endoscopy were
      randomly assigned to receive protected alendronate 70 mg/day, standard
      alendronate 70 mg/day, or placebo for 14 days. Endoscopy was repeated on days 8
      and 15. Of 78 subjects, 30 received protected alendronate, 28 received standard
      alendronate, and 20 received placebo. Mean gastric injury scores did not differ
      significantly among treatment groups. However, subjects on standard alendronate
      were more likely than those on protected alendronate to develop severe gastric
      injury, defined as Lanza score 3 or 4 (67.9% versus 33.3%, P=.009), and more
      likely to develop a gastric ulcer (21.4% versus 3.3%, P=.015). No differences in
      symptoms or adverse events were observed. In conclusion, a novel protected
      formulation of oral alendronate is less likely than standard alendronate to
      induce severe mucosal injury to the upper gastrointestinal tract.

PMID- 16642422
TI  - A multicenter, randomized, double-blind, 8-week comparative trial of standard
      doses of esomeprazole (40 mg) and omeprazole (20 mg) for the treatment of erosive
      esophagitis.
AB  - To compare esomeprazole with omeprazole for healing erosive esophagitis (EE),
      1148 patients with endoscopically confirmed EE were randomized to once-daily
      esomeprazole, 40 mg, or omeprazole, 20 mg, for 8 weeks in this multicenter,
      double-blind, parallel-group trial. The primary outcome was the proportion of
      patients with healed EE at week 8. Secondary outcomes included diary and
      investigator assessments of heartburn symptoms. At week 8, estimated healing
      rates were 92.2% (95% CI, 89.9%-94.5%) with esomeprazole and 89.8% (95% CI, 87.2%
      92.4%) with omeprazole. Healing rates with esomeprazole were significantly higher
      than those with omeprazole at weeks 8 (88.4% vs 77.5%; P = 0.007) and 4 (60.8% vs
      47.9%; P = 0.02) in patients with moderate to severe (Los Angeles grade C or D)
      EE at baseline but were not significantly different for patients with mild (Los
      Angeles grade A or B) EE. Both treatments were comparable for other secondary
      measures and had similar tolerability profiles.

PMID- 16642423
TI  - Complement activation is involved in biological responses to leukocyte adsorptive
      apheresis.
AB  - We examined the effects of complement activation on the biological responses of
      cellulose acetate (CA) beads. Peripheral blood containing the complement
      activation inhibitor nafamostat mesilate (NM) or heparin was incubated with CA
      beads in vitro. Thereafter, the fraction of adsorbed granulocytes as well as the
      generation of complement activation fragments (C3a and C5a) and interleukin 1
      receptor antagonist (IL-1ra) were measured. Granulocyte adsorption, complement
      activation, and IL-1ra release were significantly inhibited in the presence of
      NM. Adsorption was significantly increased onto CA beads pretreated with plasma
      containing heparin even in the presence of NM and adding C3a or C5a enhanced IL
      1ra release. These results suggested that bound complement fragment (e.g., C3b)
      on CA beads plays a central role in granulocyte adsorption to CA beads and that
      C3a and C5a augment the release of anti-inflammatory substances. We therefore
      conclude that complement activation is involved in these biological responses of
      leukocyte apheresis.

PMID- 16642424
TI  - Acid perfusion test: a useful test for evaluating esophageal acid sensitivity?

PMID- 16642425
TI  - Ferrus calcium citrate is absorbed better than iron bisglycinate in patients with
      Crohn's disease, but not in healthy controls.
AB  - Our purpose was to compare the absorption of iron bisglycinate and ferrous
      calcium citrate in volunteers using an oral iron tolerance test. Twenty
      volunteers, 10 healthy controls and 10 with stable Crohn's disease, agreed to
      participate in the study. All were given 50 mg of elemental iron as iron
      bisglycinate or ferrous calcium citrate. Serum iron levels were monitored for 4
      hr. After a week, each received the other regimen. Using the area under the curve
      as indicator, the oral iron absorption test revealed that absorption of iron post
      ingestion of ferrous calcium citrate was better than after ingestion of iron
      bisglycinate for the group as a whole (P < 0.03). Volunteers with Crohn's disease
      absorbed ferrous calcium citrate better than iron bisglycinate (P=0.005). No
      difference was noted in the absorption of either preparation by healthy
      volunteers. Ferrus calcium citrate is apparently more effective than iron
      bisglycinate in patients with Crohn's disease.

PMID- 16642426
TI  - Growth arrest and decrease of alpha-SMA and type I collagen expression by
      palmitic acid in the rat hepatic stellate cell line PAV-1.
AB  - Liver fibrosis is characterized by an activation of hepatic stellate cells (HSC).
      During primary culture HSC evolve from a quiescent into an activated phenotype
      which is characterized by alpha-smooth muscle actin (alpha-SMA) up-regulation,
      increase in cell growth, and extracellular matrix secretion. HSC culture with
      trans-resveratrol can lead to deactivation of myofibroblast-like HSC. We used an
      HSC line, PAV-1, to check the role of retinol and palmitic acid in the
      deactivation process of HSC. Using mass and metabolic-based methods, Western blot
      and immunocytochemistry assays, we demonstrated that treatment with palmitic acid
      (75 muM) alone or in combination with retinol (2 muM) significantly decreased
      cell proliferation and alpha-SMA expression. We also established that the
      association of both compounds strongly decreased collagen type I expression. Our
      results suggest the potential use of palmitic acid alone or in combination with
      retinol to induce HSC deactivation.

PMID- 16642427
TI  - Severe hypophosphatemia associated with gallstone pancreatitis: a case report and
      review of the literature.
AB  - Severe hypophosphatemia (<1.0 mg/dl) is a rarely reported complication of acute
      pancreatitis; when it does occur, it is typically attributed to alcohol abuse
      rather than the pancreatitis itself (1-5). In the literature, pancreatitis is not
      cited as a cause of hypophosphatemia (5, 6-16). Both pancreatitis and
      hypophosphatemia have widespread ramifications on human physiology, affecting
      hematologic, neural, hepatic, endocrine, respiratory, and renal systems. Given
      the possible synergistic consequences of pancreatitis and low serum phosphate, we
      emphasize the importance of recognizing hypophosphatemia as a complication of
      pancreatic inflammation.Herein, we report a case of acute pancreatitis unrelated
      to alcohol abuse associated with severe hypophosphatemia and review the
      pathophysiology.

PMID- 16642428
TI  - Celiac disease in African-Americans.
AB  - Celiac disease is generally under diagnosed in the United States and it is
      unclear whether the disease is encountered in ethnic minorities. Our purpose is
      to describe a case series of African-American patients with celiac disease. Nine
      (1.3%) African-American patients with celiac disease were identified from a
      prospectively generated database of 700 patients with biopsy proven celiac
      disease and seen between 1981 and 2004. Females predominated, with seven,
      compared to two males. Diarrhea was the presentation in only two patients, while
      three presented with iron deficiency anemia. One third had at least one
      autoimmune disease. Compliance with a gluten-free diet, the only medical therapy
      of this disease, was poor. Only four patients adhered strictly to the diet.
      Celiac disease occurs in African-Americans and may well be underdiagnosed.
      Special attention needs to be given to methods that encourage adherence to the
      diet in minority groups.

PMID- 16642430
TI  - Contrasting linkage-disequilibrium patterns between cases and controls as a novel
      association-mapping method.
AB  - Identification and description of genetic variation underlying disease
      susceptibility, efficacy, and adverse reactions to drugs remains a difficult
      problem. One of the important steps in the analysis of variation in a candidate
      region is the characterization of linkage disequilibrium (LD). In a region of
      genetic association, the extent of LD varies between the case and the control
      groups. Separate plots of pairwise standardized measures of LD (e.g., D') for
      cases and controls are often presented for a candidate region, to graphically
      convey case-control differences in LD. However, the observed graphic differences
      lack statistical support. Therefore, we suggest the "LD contrast" test to compare
      whole matrices of disequilibrium between two samples. A common technique of
      assessing LD when the haplotype phase is unobserved is the expectation
      maximization algorithm, with the likelihood incorporating the assumption of Hardy
      Weinberg equilibrium (HWE). This approach presents a potential problem in that,
      in the region of genetic association, the HWE assumption may not hold when
      samples are selected on the basis of phenotypes. Here, we present a
      computationally feasible approach that does not assume HWE, along with graphic
      displays and a statistical comparison of pairwise matrices of LD between case and
      control samples. LD-contrast tests provide a useful addition to existing tools of
      finding and characterizing genetic associations. Although haplotype association
      tests are expected to provide superior power when susceptibilities are primarily
      determined by haplotypes, the LD-contrast tests demonstrate substantially higher
      power under certain haplotype-driven disease models.

PMID- 16642431
TI  - Fine-mapping chromosome 20 in 230 systemic lupus erythematosus sib pair and
      multiplex families: evidence for genetic epistasis with chromosome 16q12.
AB  - The presence of systemic lupus erythematosus (SLE) susceptibility genes on
      chromosome 20 is suggested by the observation of genetic linkage in several
      independent SLE family collections. To further localize the genetic effects, we
      typed 59 microsatellites in the two best regions, as defined by genome screens.
      Genotypes were analyzed for statistical linkage and/or association with SLE, by
      use of a combination of nonparametric linkage methods, family-based tests of
      association (transmission/disequilibrium and pedigree disequilibrium tests), and
      haplotype-sharing statistics (haplotype runs test), in a set of 230 SLE
      pedigrees. Maximal evidence for linkage to SLE was to 20p12 (LOD = 2.84) and
      20q13.1 (LOD = 1.64) in the white pedigrees. Subsetting families on the basis of
      evidence for linkage to 16q12 significantly improved the LOD scores at both
      chromosome 20 locations (20p12 LOD = 5.06 and 20q13 LOD = 3.65), consistent with
      epistasis. We then typed 162 single-nucleotide polymorphism markers across a 1.3
      Mb candidate region on 20q13.1 and identified several SNPs that demonstrated
      significant evidence for association. These data provide additional support for
      linkage and association to 20p12 and 20q13.1 in SLE and further refine the
      intervals of interest. These data further suggest the possibility of epistatic
      relationships among loci within the 20q12, 20q13, and 16q12 regions in SLE
      families.

PMID- 16642432
TI  - Genomewide linkage scan for opioid dependence and related traits.
AB  - Risk of opioid dependence is genetically influenced. We recruited a sample of 393
      small nuclear families (including 250 full-sib and 46 half-sib pairs), each with
      at least one individual with opioid dependence. Subjects underwent a detailed
      evaluation of substance dependence-related traits. As planned a priori to reduce
      heterogeneity, we used cluster analytic methods to identify opioid dependence
      related symptom clusters, which were shown to be heritable. We then completed a
      genomewide linkage scan (with 409 markers) for the opioid-dependence diagnosis
      and for the two cluster-defined phenotypes represented by >250 families: the
      heavy-opioid-use cluster and the non-opioid-use cluster. Further exploratory
      analyses were completed for the other cluster-defined phenotypes. The
      statistically strongest results were seen with the cluster-defined traits. For
      the heavy-opioid-use cluster, we observed a LOD score of 3.06 on chromosome 17
      (empirical pointwise P = .0002) for European American (EA) and African American
      (AA) subjects combined, and, for the non-opioid-use cluster, we observed a LOD
      score of 3.46 elsewhere on chromosome 17 (empirical pointwise P = .00002,
      uncorrected for multiple traits studied) for EA subjects only. We also identified
      a possible linkage (LOD score 2.43) of opioid dependence with chromosome 2
      markers for the AA subjects. These results are an initial step in identifying
      genes for opioid dependence on the basis of a genomewide investigation (i.e., a
      study not conditioned on prior physiological candidate-gene hypotheses).

PMID- 16642433
TI  - Polymorphism in maternal LRP8 gene is associated with fetal growth.
AB  - Fetal growth restriction (FGR) affects >200,000 pregnancies in the United States
      annually and is associated with increased perinatal mortality and morbidity, as
      well as poorer long-term health for infants with FGR compared with infants
      without FGR. FGR appears to be a complex trait, but the role of genetic factors
      in the development of FGR is largely unknown. We conducted a candidate-gene
      association study of birth weight and FGR in two independent study samples
      obtained at the Boston Medical Center. We first investigated the association
      between maternal genotypes of 68 single-nucleotide polymorphisms (SNPs) from 41
      candidate genes and fetal growth in a sample of 204 black women selected for a
      previous study of preeclampsia, 92 of whom had preeclampsia (characterized by
      high blood pressure and the presence of protein in the urine). We found
      significant association between SNP rs2297660 in the LRP8 gene and birth weight.
      Subsequently, we replicated the association in a larger independent sample of
      1,094 black women; similar association between LRP8 and FGR was observed in this
      sample. The "A" allele at rs2297660 was associated with a higher standardized
      birth weight and a lower risk of FGR. Under the additive genetic model, each
      additional copy of the "A" allele reduced the risk of FGR by 33% (P<.05). In
      conclusion, results from the two independent samples of black women provide
      consistent evidence that SNP rs2297660 in LRP8 is associated with fetal growth.

PMID- 16642434
TI  - Efficient study designs for test of genetic association using sibship data and
      unrelated cases and controls.
AB  - Linkage mapping of complex diseases is often followed by association studies
      between phenotypes and marker genotypes through use of case-control or family
      based designs. Given fixed genotyping resources, it is important to know which
      study designs are the most efficient. To address this problem, we extended the
      likelihood-based method of Li et al., which assesses whether there is linkage
      disequilibrium between a disease locus and a SNP, to accommodate sibships of
      arbitrary size and disease-phenotype configuration. A key advantage of our method
      is the ability to combine data from different family structures. We consider
      scenarios for which genotypes are available for unrelated cases, affected sib
      pairs (ASPs), or only one sibling per ASP. We construct designs that use cases
      only and others that use unaffected siblings or unrelated unaffected individuals
      as controls. Different combinations of cases and controls result in seven study
      designs. We compare the efficiency of these designs when the number of
      individuals to be genotyped is fixed. Our results suggest that (1) when the
      disease is influenced by a single gene, the one sibling per ASP-control design is
      the most efficient, followed by the ASP-control design, and familial cases
      contribute more association information than singleton cases; (2) when the
      disease is influenced by multiple genes, familial cases provide more association
      information than singleton cases, unless the effect of the locus being tested is
      much smaller than at least one other untested disease locus; and (3) the case
      control design can be useful for detecting genes with small effect in the
      presence of genes with much larger effect. Our findings will be helpful for
      researchers designing and analyzing complex disease-association studies and will
      facilitate genotyping resource allocation.

PMID- 16642435
TI  - Cis- and trans-acting gene regulation is associated with osteoarthritis.
AB  - Osteoarthritis (OA) is a complex disease of the skeleton and is associated with
      aging. Both environmental and genetic factors contribute to its pathogenesis. We
      set out to identify novel genes associated with OA, concentrating on regulatory
      polymorphisms allowing for differential expression. Our strategy to identify
      differentially expressed genes included an initial transcriptome analysis of the
      peripheral blood mononuclear cells of six patients with OA and six age-matched
      healthy controls. These were screened for allelic expression imbalances and
      potentially regulatory single-nucleotide polymorphisms (SNPs) in the 5' regions
      of the genes. To establish disease association, disparate promoter SNP
      distributions correlating with the differential expression were tested on larger
      cohorts. Our approach yielded 26 candidate genes differentially expressed between
      patients and controls. Whereas BLP2 and CIAS1 seem to be trans-regulated, as the
      absence of allelic expression imbalances suggests, the presence of allelic
      imbalances confirms cis-regulatory mechanisms for RHOB and TXNDC3. Interestingly,
      on/off-switching suggests additional trans-regulation for TXNDC3. Moreover, we
      demonstrate for RHOB and TXNDC3 statistically significant associations between 5'
      SNPs and the disease that hint at regulatory functions. Investigating the
      respective genes functionally will not only shed light on the disease association
      but will also add to the understanding of the pathogenic processes involved in OA
      and may point out novel therapeutic approaches.

PMID- 16642436
TI  - Variation in the gene encoding the serotonin 2A receptor is associated with
      outcome of antidepressant treatment.
AB  - Depressive disorders account for a large and increasing global burden of disease.
      Although the condition of many patients improves with medication, only a minority
      experience full remission, and patients whose condition responds to one
      medication may not have a response to others. Individual variation in
      antidepressant treatment outcome is, at present, unpredictable but may have a
      partial genetic basis. We searched for genetic predictors of treatment outcome in
      1,953 patients with major depressive disorder who were treated with the
      antidepressant citalopram in the Sequenced Treatment Alternatives for Depression
      (STAR*D) study and were prospectively assessed. In a split-sample design, a
      selection of 68 candidate genes was genotyped, with 768 single-nucleotide
      polymorphism markers chosen to detect common genetic variation. We detected
      significant and reproducible association between treatment outcome and a marker
      in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers
      in HTR2A also showed evidence of association with treatment outcome in the total
      sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by
      citalopram. Participants who were homozygous for the A allele had an 18%
      reduction in absolute risk of having no response to treatment, compared with
      those homozygous for the other allele. The A allele was over six times more
      frequent in white than in black participants, and treatment was less effective
      among black participants. The A allele may contribute to racial differences in
      outcomes of antidepressant treatment. Taken together with prior neurobiological
      findings, these new genetic data make a compelling case for a key role of HTR2A
      in the mechanism of antidepressant action.

PMID- 16642437
TI  - Serotonin transporter promoter gain-of-function genotypes are linked to obsessive
      compulsive disorder.
AB  - A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk
      of disease as well as brain morphometry and function. Here, we show that HTTLPR
      is functionally triallelic. The L(G) allele, which is the L allele with a common
      G substitution, creates a functional AP2 transcription-factor binding site.
      Expression assays in 62 lymphoblastoid cell lines representing the six genotypes
      and in transfected raphe-derived cells showed codominant allele action and low,
      nearly equivalent expression for the S and L(G) alleles, accounting for more
      variation in HTT expression than previously recognized. The gain-of-function
      L(A)L(A) genotype was approximately twice as common in 169 whites with obsessive
      compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a
      replication study in 175 trios consisting of probands with OCD and their parents.
      The L(A) allele was twofold overtransmitted to the patients with OCD. The HTTLPR
      L(A)L(A) genotype exerts a moderate (1.8-fold) effect on risk of OCD, which
      crystallizes the evidence that the HTT gene has a role in OCD.

PMID- 16642438
TI  - Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1
      gene.
AB  - Previous studies have narrowed the interval containing PSORS1, the psoriasis
      susceptibility locus in the major histocompatibility complex (MHC), to an
      approximately 300-kb region containing HLA-C and at least 10 other genes. In an
      effort to identify the PSORS1 gene, we cloned and completely sequenced this
      region from both chromosomes of five individuals. Two of the sequenced haplotypes
      were associated with psoriasis (risk), and the other eight were clearly
      unassociated (nonrisk). Comparison of sequence of the two risk haplotypes
      identified a 298-kb region of homology, extending from just telomeric of HLA-B to
      the HCG22 gene, which was flanked by clearly nonhomologous regions. Similar
      haplotypes cloned from unrelated individuals had nearly identical sequence.
      Combinatorial analysis of exonic variations in the known genes of the candidate
      interval revealed that HCG27, PSORS1C3, OTF3, TCF19, HCR, STG, and HCG22 bore no
      alleles unique to risk haplotypes among the 10 sequenced haplotypes. SPR1 and
      SEEK1 both had messenger RNA alleles specific to risk haplotypes, but only HLA-C
      and CDSN yielded protein alleles unique to risk. The risk alleles of HLA-C and
      CDSN (HLA-Cw6 and CDSN*TTC) were genotyped in 678 families with early-onset
      psoriasis; 620 of these families were also typed for 34 microsatellite markers
      spanning the PSORS1 interval. Recombinant haplotypes retaining HLA-Cw6 but
      lacking CDSN*TTC were significantly associated with psoriasis, whereas
      recombinants retaining CDSN*TTC but lacking HLA-Cw6 were not associated, despite
      good statistical power. By grouping recombinants with similar breakpoints, the
      most telomeric quarter of the 298-kb candidate interval could be excluded with
      high confidence. These results strongly suggest that HLA-Cw6 is the PSORS1 risk
      allele that confers susceptibility to early-onset psoriasis.

PMID- 16642439
TI  - Cigarette smoking strongly modifies the association of LOC387715 and age-related
      macular degeneration.
AB  - We used iterative association mapping to identify a susceptibility gene for age
      related macular degeneration (AMD) on chromosome 10q26, which is one of the most
      consistently implicated linkage regions for this disorder. We employed linkage
      analysis methods, followed by family-based and case-control association analyses,
      using two independent data sets. To identify statistically the most likely AMD
      susceptibility allele, we used the Genotype-IBD Sharing Test (GIST) and
      conditional haplotype analysis. To incorporate the two most important known AMD
      risk factors--smoking and the Y402H variant of the complement factor H gene (CFH)
      -we used logistic regression modeling to test for gene-gene and gene-environment
      interactions in the case-control data set and used the ordered-subset analysis to
      account for genetic linkage heterogeneity in the family-based data set. Our
      results strongly implicate a coding change (Ala69Ser) in the LOC387715 gene as
      the second major identified AMD-susceptibility allele, confirming earlier
      suggestions. This variant's effect on AMD is statistically independent of CFH and
      is of similar magnitude to the effect of Y402H. The overall effect is driven
      primarily by a strong association in smokers, since we observed significant
      evidence for a statistical interaction between the LOC387715 variant and a
      history of cigarette smoking. This gene-environment interaction is supported by
      statistically independent family-based and case-control analysis methods. We
      estimate that CFH, LOC387715, and cigarette smoking together explain 61% of the
      population-attributable risk (PAR) of AMD. The adjusted PAR percentage estimates
      are 20% for smoking, 36% for LOC387715, and 43% for CFH. We demonstrate, for the
      first time, that a genetic susceptibility coupled with a modifiable lifestyle
      factor such as cigarette smoking confers a significantly higher risk of AMD than
      either factor alone.

PMID- 16642440
TI  - Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient
      Niemann-Pick disease.
AB  - Acid sphingomyelinase (ASM) is the lipid hydrolase that is deficient in types A
      and B Niemann-Pick disease (NPD). Here, we demonstrate that the gene encoding ASM
      (SMPD1) is paternally imprinted and that differential expression of the mutant
      alleles in patients with ASM-deficient NPD and in carriers influences the disease
      phenotype. Comparison of the results of genomic sequencing versus reverse
      transcriptase polymerase chain reaction sequencing for several patients with NPD
      revealed preferential expression of one mutant allele. Further analysis of one
      family showed that the expressed allele was maternally inherited and that the
      distinct clinical presentations of the individual patients were correlated with
      the amount of residual ASM activity expressed from the maternal mutation.
      Treatment of NPD cell lines with 5-aza-2'-deoxycytidine enhanced the expression
      of the paternal SMPD1 allele, and bisulfite genomic sequencing identified which
      CpG dinucleotides within the SMPD1 promoter were methylated. In a related set of
      studies, we identified a carrier individual who had approximately 15% of normal
      ASM activity and clinical features of ASM-deficient NPD. DNA sequencing confirmed
      that this individual carried a single SMPD1 mutation and that this mutant allele
      was preferentially expressed. These data thus demonstrate, for the first time,
      imprinting at the SMPD1 gene and reveal the influence of this epigenetic
      modification on the presentation of ASM-deficient NPD.

PMID- 16642441
TI  - Association of polymorphisms in the Angiotensin-converting enzyme gene with
      Alzheimer disease in an Israeli Arab community.
AB  - Several lines of evidence support for a role of angiotensin converting enzyme
      (ACE) in Alzheimer disease (AD). Most genetic studies have focused on an Alu
      insertion/deletion (I/D) polymorphism in the ACE gene (DCP1) and have yielded
      conflicting results. We evaluated the association between 15 single-nucleotide
      polymorphisms (SNPs) in DCP1, including the I/D variant, and AD in a sample of 92
      patients with AD and 166 nondemented controls from an inbred Israeli Arab
      community. Although there was no evidence for association between AD and I/D, we
      observed significant association with SNPs rs4343 (P = .00001) and rs4351 (P =
      .01). Haplotype analysis revealed remarkably significant evidence of association
      with the SNP combination rs4343 and rs4351 (global P = 7.5 x 10(-7)). Individuals
      possessing the haplotype "GA" (frequency 0.21 in cases and 0.01 in controls)
      derived from these SNPs had a 45-fold increased risk of developing AD (95% CI 6.0
      343.2) compared with those possessing any of the other three haplotypes. Longer
      range haplotypes including I/D were even more significant (lowest global P = 1.1
      x 10(-12)), but the only consistently associated alleles were in rs4343 and
      rs4351. These results suggest that a variant in close proximity to rs4343 and
      rs4351 modulates susceptibility to AD in this community.

PMID- 16642442
TI  - Breakpoint cloning and haplotype analysis indicate a single origin of the common
      Inv(10)(p11.2q21.2) mutation among northern Europeans.
AB  - The pericentric inv(10)(p11.2q21.2) mutation has been frequently identified in
      cytogenetic laboratories, is phenotypically silent, and is considered to be a
      polymorphic variant. Cloning and sequencing of the junction fragments on 10p11
      and 10q21 revealed that neither inversion breakpoint directly involved any genes
      or repetitive sequences, although both breakpoint regions contain a number of
      repeats. All 20 apparently unrelated inv(10) families in our study had identical
      breakpoints, and detailed haplotype analysis showed that the inversions were
      identical by descent. Thus, although considered a common variant,
      inv(10)(p11.2q21.2) has a single ancestral founder among northern Europeans.

PMID- 16642443
TI  - Coverage and power in genomewide association studies.
AB  - The ability of genomewide association studies to decipher genetic traits is
      driven in part by how well the measured single-nucleotide polymorphisms "cover"
      the unmeasured causal variants. Estimates of coverage based on standard linkage
      disequilibrium measures, such as the average maximum squared correlation
      coefficient (r2), can lead to inaccurate and inflated estimates of the power of
      genomewide association studies. In contrast, use of the "cumulative r2 adjusted
      power" measure presented here gives more-accurate estimates of power for
      genomewide association studies.

PMID- 16642444
TI  - Quantification of homozygosity in consanguineous individuals with autosomal
      recessive disease.
AB  - Individuals born of consanguineous union have segments of their genomes that are
      homozygous as a result of inheriting identical ancestral genomic segments through
      both parents. One consequence of this is an increased incidence of recessive
      disease within these sibships. Theoretical calculations predict that 6% (1/16) of
      the genome of a child of first cousins will be homozygous and that the average
      homozygous segment will be 20 cM in size. We assessed whether these predictions
      held true in populations that have preferred consanguineous marriage for many
      generations. We found that in individuals with a recessive disease whose parents
      were first cousins, on average, 11% of their genomes were homozygous (n = 38;
      range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM
      (n = 38; range of number of homozygous segments 7-32), and that the size of the
      homozygous segment associated with recessive disease was 26 cM (n = 100; range 5
      70 cM). These data imply that prolonged parental inbreeding has led to a
      background level of homozygosity increased approximately 5% over and above that
      predicted by simple models of consanguinity. This has important clinical and
      research implications.

PMID- 16642445
TI  - [Is there room for the pediatric neurological examination in the 21st century? A
      contribution to clinical research on development].
AB  - AIM: To underscore the importance of the pediatric neurological examination for
      the diagnosis, treatment and prognosis of nervous system disorders in children.
      For that, we reviewed the research carried out by our group in the past 40 years.
      DEVELOPMENT: Knowing the semiology of neurological development is essential for
      the neurological, psychological and motor follow-up of children. On their own,
      neuroimaging techniques are not sufficient to predict the long-term neurological
      and psychomotor consequences of perinatal events. On the other hand, the
      neurological examination is a sensitive method with good prognostic value, which
      facilitates a timely and appropriate treatment intervention. This observation has
      been confirmed by our research focused on the neurological examination, including
      the study of the developmental neurological examination in preschoolers,
      assessment of the psychological and neurological maturity in school age children,
      development of preterm-born school age children, limb-trunk coordination in
      premature newborns and their development, relationship between higher brain
      function, learning to read and write and improving the diagnosis of attention
      deficit/hyperactivity disorder in school children, neurological disorders in
      newborns, birth trauma, jaw opening reflex to appendicular compression, parachute
      and lateral propping reactions in newborns, neurological and psychomotor
      development at 6 months of corrected age in premature babies with neonatal crises
      and/or intracranial hemorrhage, and neurological examination in healthy newborns.
      CONCLUSIONS: The neuropediatrician must be aware of the importance of a
      comprehensive neurological history and consistent semiology to be able to request
      and correctly evaluate the results of ancillary tests, and thus make adequate
      treatment decisions.

PMID- 16642446
TI  - [Treatment of herpes simplex encephalitis in children].
AB  - INTRODUCTION: Herpes simplex encephalitis (HSE) is a focal infectious disease of
      the central nervous system (CNS) acknowledged the world over as being severe.
      DEVELOPMENT: The epidemiology is well known in developed countries. It presents
      in patients over the age of 3 months. The mechanism by which the virus
      reactivates and penetrates into the CNS is still not fully understood. A timely
      diagnosis is crucial so that early treatment can be established within the first
      four days of the infectious process. By so doing, it becomes possible to raise
      the chances of survival by over 50%. The physician should have a strong suspicion
      when faced with a patient with symptoms of encephalitis, especially if he or she
      has focal neurological manifestations, including manifestations in the
      neuropsychiatric sphere. The non-invasive diagnostic method par excellence is
      high-sensitivity magnetic resonance imaging studies of the brain within the first
      24-48 hours following the onset of the clinical signs and symptoms. Determination
      of viral DNA in cerebrospinal fluid by the polymerase chain reaction method is
      the technique with the highest degree of sensitivity and specificity available
      for carrying out the diagnosis. Effective treatment is intravenous acyclovir: 30
      mg/kg/day in three doses. CONCLUSIONS: Encephalitis produced by the herpes virus
      is a disease that is dreaded because of the high mortality rate and the
      devastation it causes in the living conditions of survivors. Our aim is to
      stimulate the clinical suspicion of HSE so that pharmacological treatment can be
      established even while diagnostic tests are being carried out. We suggest early
      neuropsychological evaluation and follow-up of the manifestations of focal
      sequelae related to the frontotemporal regions.

PMID- 16642447
TI  - [The role played by calcium in neuronal injury following neonatal hypoxia or
      convulsions].
AB  - AIM: Calcium plays a complex and pivotal role both in neuronal development and
      function, and in hypoxia/ ischemia-induced cell death. In this paper, we review
      current concepts of calcium function emphasizing the neonatal period.
      DEVELOPMENT: Calcium enters the neuron through glutamate receptors (NMDA and
      AMPA) located on the neuronal membrane. After hypoxia or seizures, there is a
      conformational change of the receptors, with increased flow of calcium into the
      cytoplasm. Cytoplasmatic calcium triggers activation of several free-radical
      generation pathways, including the nitric oxide pathway, with a deleterious
      effect upon the neuron. Calcium then enters the neuronal nucleus, through
      specific receptors on the nuclear membrane. In our experience, hypoxia and
      neonatal seizures create nuclear membrane dysfunction, increasing the nitric
      oxide-dependent flow of calcium into the nucleus. Nuclear calcium increase is
      critical for genetic transcription, pro-apoptotic gene activation and a cascade
      of biochemical and molecular events that lead to an increase of caspases and
      apoptotic neuronal death. CONCLUSIONS: Calcium has a crucial role in neuronal
      damage after neonatal hypoxia or seizures. A better knowledge of the pathogenic
      mechanisms that lead to neuronal damage after neonatal hypoxia or seizures will
      assist in future development of efficacious neuroprotective therapies.

PMID- 16642448
TI  - [Cerebrovascular accidents in full-term newborn infants].
AB  - INTRODUCTION: The purpose of this paper is to review the role of the neurologist
      in the management of cerebrovascular accidents (CVA) (insults resulting from a
      sudden obstruction or rupture of an intracranial vessel). This was accomplished
      by reviewing the literature (PubMed) under the heading of stroke and term
      neonate. DEVELOPMENT: CVA in full-term neonates are classified as hematomas and
      infarcts. Hematomas are classified according to: location, structure (arterial,
      venous, or sinus), type of malformation (aneurysm, venous malformation, and
      telangiectasia), and cause of the bleed (vessel wall rupture or hypo
      coagulation). Classification according to location is based on compartment supra
      or infratentorial; space -extra-axial (epidural, subdural, or subarachnoid) or
      intra-axial (parenchymal or ventricular)-; and region -parietal, temporal,
      thalamic, etc.-. Infarcts are classified according to vascular and parenchymal
      factors. The vascular factors are the structure, the cause of the obstruction 
      extramural, mural or intramural (thrombus or embolus)-. The parenchymal factors
      are type of damage (pale vs hemorrhagic) and location. Patients with suspected
      embolism should have ultrasound neck. Coagulation studies should be done in
      patients with hematomas and infracts. Multiple causes may be present in each
      case. Anticoagulation is only used in small pale infarcts of cardiac embolic
      origin. CONCLUSION: The neurologist roles in the management of CVA are to
      classify the event, select the appropriate investigation, and implement
      treatment.

PMID- 16642449
TI  - [Cerebrovascular disorders in preterm neonates].
AB  - AIM: To review the etiology, pathogenesis, clinical manifestations, diagnosis and
      treatment of cerebrovascular disorders (CVD) in preterm neonates. DEVELOPMENT:
      The germinal matrix-intraventricular hemorrhage (GM-IVH) is the most frequent
      intracranial hemorrhage. The pathogenesis includes intravascular, vascular and
      extravascular factors. The neuropathologic lesion is the hemorrhage within the
      subependymal GM. There are four degrees of severity. Clinical manifestations
      include three syndromes: catastrophic, saltatory and silent. Treatment is
      prophylactic. Periventricular hemorrhagic infarct is of venous origin, might be
      associated to GM-IVH and is difficult to differentiate from periventricular
      leukomalacia (PVL). Cerebellar hemorrhage frequency increases with decreasing
      gestational age. It may be asymptomatic or manifest with a non-specific
      neurologic picture. PVL is the most important ischemic lesion. Its pathogenesis
      includes anatomic, physiologic, maturational, biochemical, infectious and
      immunologic factors. The neuropathologic lesion is focal necrosis in the terminal
      distribution of the long penetrating arteries. Treatment is prophylactic. Other
      ischemic lesions are ischemic arterial infarct, cerebellar infarct, telencephalic
      leukoencephalopathy and pontosubicular necrosis. CVD diagnostic tests include
      cerebral ultrasound, computed tomography, magnetic resonance imaging and
      spectroscopy and electroencephalogram. Mortality of some CVD is high and some
      others are associated with a high risk of cerebral palsy and cognitive deficits.
      CONCLUSION: CVD are common in preterm neonates and represent an important cause
      of neurologic disease in the child.

PMID- 16642450
TI  - [Congenital hydrocephalus].
AB  - INTRODUCTION: Congenital hydrocephalus or ventriculomegaly is a disorder that now
      can be diagnosed in uterus with ultrasonography, this gives the chance of being
      able to give a treatment the earliest as possible. DEVELOPMENT: The clinical
      manifestations are reviewed, the diagnosis, the frequent treatment and causes of
      congenital hydrocephalus, being the first agenesis of the Sylvius' aqueduct,
      followed by Arnold-Chiari's malformations with mielomeningocele. CONCLUSIONS: In
      most of the cases the peritoneal-ventricle shunt is the best surgery treatment
      and now, the treatment with ventriculostomy of third ventricle by endoscopy has
      fewer complications apparently and in several cases it is the definitive
      treatment. The evolution of the diagnosis with the support of specific therapies
      is effective and the early treatment is good, of course taking into account the
      etiology.

PMID- 16642451
TI  - [Executive function disorders].
AB  - AIM: To review the development, anatomy and physiology of executive functions
      (EF) in normal and pathological conditions. DEVELOPMENT: EF consist of several
      internal mental process design to solve mental and environmental complex problems
      in an efficient and acceptable way to the person and the society. EF include
      inhibition of behavior and irrelevant information, nonverbal working memory,
      verbal working memory, self-regulation of affect, motivation and arousal,
      planning, decision making, self monitoring of the entire solving problem process
      and self evaluation of the results of the action taken. The anatomical substrate
      is at the prefrontal lobe cortex and its afferent and efferent structures.
      Neurotransmitters involved in activation of neurons at the prefrontal cortex are
      dopamine and norepinephrine and in less degree acetylcholine and serotonine.
      CONCLUSIONS: Disorders of one or more of the EF in children and adolescents are
      found in attention deficit/hyperactivity disorder, Tourette syndrome, bipolar
      disease, depression, obsessive-compulsive disorders, autism and traumatic brain
      injury.

PMID- 16642452
TI  - [Atentional processes and attention deficit disorders in autism].
AB  - INTRODUCTION: Autism is recognised as being a behavioural syndrome characterised
      by impaired language development, restricted interests and compromised
      socialisation. It is accepted that persons with autism react in an inappropriate
      way to socially relevant information and that they are unable to benefit from
      important stimuli from their surroundings. A number of disorders affecting
      different attention processes (with the ensuing difficulty involved in selecting
      and hierarchising stimuli) have been put forward as probable hypotheses to
      account for the genesis of these problems. DEVELOPMENT: In this work we analyse
      some of the attentional processes reported as being due to deficits in autism
      (disorders affecting alertness, orientation, gaze, sustained attention and
      changes in focus of attention). We also examine the high rate of comorbidity of
      attention deficit disorders with or without hyperactivity (ADHD) with pervasive
      developmental disorders (PDD) and the importance of identifying them.
      CONCLUSIONS: Although many disorders affecting the components of attention have
      been reported, the findings and their importance are controversial and it is
      likely that their association to other cognitive disorders plays an important
      role in the development of autism. With regard to the association between ADHD
      and PDD, it is an acknowledged fact that up to 70% of the persons with PDD meet
      ADHD criteria; whether we are before a situation of comorbidity, it is part of
      the spectrum or forms a specific subtype is an interesting issue for debate.
      Nevertheless, what is essential is for this association to be acknowledged to
      allow therapy to be undertaken using the correct approach.

PMID- 16642453
TI  - [Risks and benefits of the new antiepileptic drugs].
AB  - INTRODUCTION: More new antiepileptic drugs (AED) have been introduced over the
      last decade than in the past 40 years -a fact that has improved our therapeutic
      capabilities, especially in the case of refractory epilepsies. DEVELOPMENT: The
      new AED, generally speaking, have a longer half-life, lower rate of protein
      attachment and a fewer side affects, and interaction takes place to a lesser
      extent either with other AED and drugs. Yet, paediatric formulations are few,
      costs are high in developing countries and in such countries their use is often
      limited by the fact that they are simply not available. CONCLUSIONS: The new AED
      offer a number of advantages over the classical agents as far as pharmacokinetics
      and metabolism are concerned, since they do not interact with other medications
      so frequently. Despite the high economic cost for developing countries, the
      general impression is that they do indeed reduce the social cost.

PMID- 16642454
TI  - [Indications and outcomes of epilepsy surgery in children].
AB  - INTRODUCTION: One in every four children who suffer epilepsy will continue to
      seize despite all the current arsenal of anticonvulsant medications. Epilepsy
      surgery can be an effective treatment for many cases of pharmaco-resistant
      epilepsy. AIM: To review some of the most recent data regarding indication and
      results for epilepsy surgery in children. DEVELOPMENT: New analysis of
      neurophysiological data such as magnetoencephalography, dipole analysis and high
      frequency oscillations, plus functional neuroimaging and higher resolution MRI,
      have improved the prompt referral of potential candidates for surgery. An
      adequate selection of the surgical candidates will be fundamental in obtaining
      positive outcomes. Children, just like adults, can achieve seizure freedom or
      more than 90% seizure reduction in 85% of the cases of temporal lobe resections.
      Extratemporal epilepsy surgery is more challenging, and presents frequently in
      epilepsy surgery centres specialized in pediatric care. CONCLUSION: It is not
      mandatory for a patient to have an structural lesion evident on MRI in order to
      be considered a candidate for epilepsy surgery. In many cases a partial reduction
      of seizure activity can significantly improve the patient's and family's quality
      of life, and can have a sinergistic effect with other therapies which were no
      effective before surgery.

PMID- 16642455
TI  - [Paediatric pseudotumour cerebri].
AB  - INTRODUCTION: Paediatric pseudotumour cerebri or idiopathic intracranial
      hypertension syndrome is rare in the paediatric age and presents with clinical
      features that differ from the clinical picture seen in adults. It is not a benign
      condition in children and, although sometimes used to identify this syndrome, the
      term 'benign intracranial hypertension' must therefore be avoided. It is
      characterised by an increase in the intracranial pressure with analytically
      normal cerebrospinal fluid and the absence of expansive injuries detected by
      means of neuroimaging. DEVELOPMENT: It is a complex syndrome that causes intense
      headaches in children with acute loss of vision and, on occasions, optic atrophy.
      Its treatment has to be tailored to each patient and the use of different
      pharmacological or neurosurgical treatments must be considered to avoid permanent
      visual damage. We reviewed the case mix at our Institute over the last 10 years
      (1995-2005) and found 23 children (between 3 and 15 years of age) who fulfilled
      Dandy criteria confirming a diagnosis as suffering from paediatric pseudotumour
      cerebri, with no predominance of sex or associated obesity. CONCLUSIONS: Its
      treatment must be established on an individualised basis, as well as ongoing and
      multidisciplinary; fenestration of the optic nerve sheath or the implantation of
      lumboperitoneal shunts correct refractory syndromes, which in our case accounted
      for 35% of the total number. The rest were treated with acetazolamide, diet and
      steroids.

PMID- 16642456
TI  - [Acute disseminated encephalomyelitis in children].
AB  - AIM: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated
      inflammatory-demyelinating disease, which usually follows an infection or
      vaccination. It is more frequent in children. In this paper, I will review
      clinical, diagnosis, treatment, and prognosis data, based on last 10 years
      papers, including our experience with 42 patients studied at Calvo Mackenna
      Hospital and German Clinic of Santiago de Chile, Chile. DEVELOPMENT: ADEM
      symptoms present 2 to 30 days after viral or bacterial infection. There is a
      slight male predominance (1,3:1). The clinical picture is characterized by
      multiple symptoms. Prominent findings are altered level of consciousness in 50
      60% of patients, and motor system dysfunction in 80-90%. Spinal cord dysfunction
      occurs in 20-25% of children. Optic neuritis (10-20%) is usually bilateral.
      Magnetic resonance imaging is the gold standard to detect typical white matter
      lesions, which suggest ADEM diagnosis, but a clinico-neuroimaging gap may occurs.
      Steroids are the first choice for treatment. In practice, they seem to be useful
      in up to 90% of patients. Recurrences occur in 10-30% of cases, and raise a
      differential diagnosis with multiple sclerosis. Mortality is as low as 0-7%.
      Sequelae are seen in 10-20% of patients. CONCLUSIONS: ADEM is a demyelinating
      condition, usually with a monophasic course and good outcome. The only way to
      confirm a definite diagnosis is long-term follow-up.

PMID- 16642457
TI  - [Paroxysmal neurogenetic and neurometabolic disorders].
AB  - AIM: To provide an overview of those neurological disorders that are mainly
      characterized by a paroxysmal pattern of involvement, and in which a clear
      genetic or metabolic etiology has been identified. DEVELOPMENT: The term
      'paroxysmal' refers to the abrupt onset of clinical manifestations in a
      relatively stereotyped manner, usually upon exposure to specific triggering
      factors with an almost complete resolution of such findings between attacks. They
      are commonly not associated to either a relentless progression or a stepwise
      deterioration, and the majority of them do not lead to the development of gross
      neuropathological abnormalities. Although they are difficult to classify due to
      the heterogeneity of their clinical manifestations and underlying deficits, a
      neuroaxis-based approach is proposed for practical purposes, for example, from
      those conditions affecting predominantly cortical grey matter (manifesting mainly
      with seizures) to those with an almost exclusive muscular and/or neuromuscular
      pattern of involvement. The majority of them are caused by genetic defects in
      either transporters or neuronal channels, which can be either ions or
      neurotransmitters. In recent years, the concept of 'channelopathies' has grown in
      acceptance in the medical field, although not all of the described disorders are
      caused by defects in molecular channels. CONCLUSIONS: Despite their individual
      rarity, as a group, they are important to the neurologist due to the advances
      that their understanding have provided for the development of the field of
      neurogenetics and neurosciences in general.

PMID- 16642458
TI  - Neuroborreliosis and the pediatric population: a review.
AB  - AIMS: To review the medical literature on neuroborreliosis, in particular its
      clinical features in both adults and children, and highlight the differences
      between the two groups, with an emphasis on the pediatric population.
      DEVELOPMENT: The neurologic manifestations of the disease variably affect
      different areas of the neuroaxis, central or peripheral, and can present with
      early or late symptomatology, depending on the age group. Although the literature
      includes a wide range of neurologic abnormalities, the most frequent symptom
      reported in the pediatric population is headache, and the most common sign being
      facial palsy. An immunologic process with cross-reacting antibodies and
      antibodies directed against neuronal proteins may exist as the causative factor.
      Because of characteristic cerebrospinal fluid (CSF) findings, CSF examination and
      serologic testing for Borrelia burgdorferi, the causative agent, should be
      performed in patients, particularly if a child, having been in an endemic area,
      presenting with an acute neurologic disorder of unexplained etiology. Treatment
      with antibiotics, if initiated early-on, is curative, especially in children.
      CONCLUSIONS: The pediatric population carries the highest risk for Lyme disease
      relative to other age groups. Younger patients tend to be more acutely affected,
      with involvement primarily of the central nervous system, exhibiting an
      inflammatory response in the CSF and signs/symptoms of aseptic meningitis and
      facial nerve palsy, whereas older patients present with features of peripheral
      nervous system pathology, tipically with a radiculopathy. Despite having a
      greater incidence of neuroborreliosis, the clinical course in most children is
      milder and shorter than that reported for adults.

PMID- 16642459
TI  - [Neurocysticercosis in children: clinical study and follow-up of 112 patients].
AB  - INTRODUCTION: Neurocysticercosis (NC) is the infection of the central nervous
      system caused by the Taenia solium larva. It is related to a wide variety of
      clinical symptoms and pathological findings. AIM: Clinical study, diagnosis,
      treatment and evolution of 112 patients with NC. PATIENTS AND METHODS: 112
      patients with NC, between 1 and 14 years of age, were evaluated and followed from
      18 months up to 13 years. RESULTS: The most common clinical symptoms were
      epileptic seizures and signs of intracranial hypertension. The disease progressed
      as follows: active forms were seen in around 39% of the cases (viable cysts in 3%
      and transitional/granulomatous form in 36%), encephalitic form in 22% and
      inactive form (calcifications) in 39%. In the great majority of the cases, a
      treatment with anti-helmitic was not used. The control of the crises was positive
      in 86% of the cases -94% in the transitional forms, 93% in the inactive forms and
      68% in the encephalitic form-. Recurrence of crises happened after suspension of
      the medication in 12,5% of the granulomatous form and in 11,2% of the inactive
      form. Neurological sequelae occurred only in the encephalitic form (12/25
      patients). CONCLUSIONS: Clinical findings and clinical evolution of
      neurocysticercosis in children is related to the evolutive form of the disease.
      The clinical evolution, including control of the crises and radiological control,
      is benign in the inactive and active forms, except in the encephalitic forms. The
      extraparenquimatous form is quite rare in the pediatric group.

PMID- 16642460
TI  - Optimal classification of long echo time in vivo magnetic resonance spectra in
      the detection of recurrent brain tumors.
AB  - We describe the optimal high-level postprocessing of single-voxel (1)H magnetic
      resonance spectra and assess the benefits and limitations of automated methods as
      diagnostic aids in the detection of recurrent brain tumor. In a previous clinical
      study, 90 long-echo-time single-voxel spectra were obtained from 52 patients and
      classified during follow-up (30/28/32 normal/non-progressive tumor/tumor). Based
      on these data, a large number of evaluation strategies, including both standard
      resonance line quantification and algorithms from pattern recognition and machine
      learning, were compared in a quantitative evaluation. Results from linear and non
      linear feature extraction, including ICA, PCA and wavelet transformations, and
      also the data from resonance line quantification were combined systematically
      with different classifiers such as LDA, chemometric methods (PLS, PCR), support
      vector machines and ensemble methods. Classification accuracy was assessed using
      a leave-one-out cross-validation scheme and the area under the curve (AUC) of the
      receiver operator characteristic (ROC). A regularized linear regression on
      spectra with binned channels reached 91% classification accuracy compared with
      83% from quantification. Interpreting the loadings of these regressions, we find
      that lipid and lactate signals are too unreliable to be used in a simple machine
      rule. Choline and NAA are the main source of relevant information. Overall, we
      find that fully automated pattern recognition algorithms perform as well as, or
      slightly better than, a manually controlled and optimized resonance line
      quantification.

PMID- 16642461
TI  - Deviation from the mobile proton model in amino-modified peptides: implications
      for multiple reaction monitoring analysis of peptides.
AB  - The study of peptide fragmentation is important to the understanding of chemical
      processes occurring in the gas phase and the more practical concern of peptide
      identification for proteomic analysis. Using the mobile proton model as a
      framework, we explore the effect of amino-group modifications on peptide
      fragmentation. Three aldehydes are used to transform the peptides' primary amino
      groups into either a dimethylamino or a heterocyclic structure (five- or six
      membered). The observed fragmentation patterns deviate strongly from those
      observed for the analogous underivatised peptides. In particular, the a1 ion is
      the base peak in most tandem mass spectra of the derivatised peptides. The a1 ion
      intensity depends strongly on the N-terminal amino acid, with tyrosine and
      phenylalanine having the strongest enhancement. Despite the change in
      fragmentation patterns of the derivatised peptides, they still provide high
      quality tandem mass spectra that, in many cases, are more amenable to database
      searching than the spectra of underivatised peptides. In addition, the reliable
      presence of the a1 ion facilitates rapid quantitative measurements using the
      multiple reaction monitoring approach.

PMID- 16642462
TI  - A gated 31P NMR method for the estimation of phosphocreatine recovery time and
      contractile ATP cost in human muscle.
AB  - Muscle phosphocreatine (PCr) recovery time constant (an index of muscle aerobic
      capacity) and contractile ATP cost were estimated from a gated (31)P NMR protocol
      which does not require intense, repetitive exercise. Subjects performed 2-s
      duration, maximum voluntary isometric ankle dorsiflexion contractions at 30-s
      intervals for 8 min (total 15 contractions), while single-shot (31)P spectra
      (51.7 MHz, TR 3 s) were acquired from the anterior compartment muscle. Spectra
      from the sixth through 15th contractions were retrospectively sorted, yielding 10
      spectra (each 10 averages) gated to times before and after contraction. There was
      no significant decrease in muscle pH, allowing the calculation of contractile ATP
      cost directly from the percentage change in PCr during contraction cycles [8.86
      +/- 0.82% (SE, n = 11) of PCr at rest], corresponding to an ATP cost of 1.69 +/-
      0.16 mM/s (range 0.99-2.49 mM/s), assuming an 8.2 mM ATP concentration. The time
      constant for PCr recovery (tau 41.8 +/- 4.2 s, range 22.0-60.8 s) was calculated
      from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in PCr due to
      contraction, D is the additional steady-state percentage drop in PCr from rest
      and Deltat is the interval between contractions. In the same subjects, the
      monoexponential PCr recovery time constant after more intense, repetitive
      isometric ankle dorsiflexion exercise (30 s at 0.5 Hz, 50% duty cycle) was
      similar to (36.2 +/- 3.5 s, range 16.5-58.8 s) and well correlated with (r =
      0.82) the gated result. In contrast to the gated protocol, muscle pH decreased
      from 7.01 +/- 0.01 to 6.78 +/- 0.04 during recovery after the repetitive
      protocol. Hence the gated protocol allows the estimation of muscle ATP cost and
      PCr recovery without intense exercise or muscle acidification.

PMID- 16642463
TI  - Analysis of carbohydrates and glycoconjugates by matrix-assisted laser
      desorption/ionization mass spectrometry: An update covering the period 1999-2000.
AB  - This review describes the use of matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry for the analysis of carbohydrates and glycoconjugates
      and continues coverage of the field from the previous review published in 1999
      (D. J. Harvey, Matrix-assisted laser desorption/ionization mass spectrometry of
      carbohydrates, 1999, Mass Spectrom Rev, 18:349-451) for the period 1999-2000. As
      MALDI mass spectrometry is acquiring the status of a mature technique in this
      field, there has been a greater emphasis on applications rather than to method
      development as opposed to the previous review. The present review covers
      applications to plant-derived carbohydrates, N- and O-linked glycans from
      glycoproteins, glycated proteins, mucins, glycosaminoglycans, bacterial
      glycolipids, glycosphingolipids, glycoglycerolipids and related compounds, and
      glycosides. Applications of MALDI mass spectrometry to the study of enzymes
      acting on carbohydrates (glycosyltransferases and glycosidases) and to the
      synthesis of carbohydrates, are also covered.

PMID- 16642464
TI  - Nitric oxide contributes to the development of a post-injury Th2 T-cell phenotype
      and immune dysfunction.
AB  - Severe injury induces immune dysfunction resulting in increased susceptibility to
      opportunistic infections. Previous studies from our laboratory have demonstrated
      that post-burn immunosuppression is mediated by nitric oxide (NO) due to the
      increased expression of macrophage inducible nitric oxide synthase (iNOS). In
      contrast, others suggest that injury causes a phenotypic imbalance in the
      regulation of Th1- and Th2 immune responses. It is unclear whether or not these
      apparently divergent mediators of immunosuppression are interrelated. To study
      this, C57BL/6 mice were subjected to major burn injury and splenocytes were
      isolated 7 days later and stimulated with antiCD3. Burn injury induced NO
      mediated suppression of proliferative responses that was reversed in the presence
      of the NOS inhibitor L-monomethyl-L-arginine and subsequently mimicked by the
      addition of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). SNAP also dose
      dependently suppressed IFN-gamma and IL-2 (Th1), but not IL-4 and IL-10 (Th2)
      production. Delaying the addition of SNAP to the cultures by 24 h prevented the
      suppression of IFN-gamma production. The Th2 shift in immune phenotype was
      independent of cGMP and apoptosis. The addition of SNAP to cell cultures also
      induced apoptosis, attenuated mitochondrial oxidative metabolism and induced
      mitochondrial membrane depolarization. However, these detrimental cellular
      effects of NO were observed only at supra-physiologic concentrations (>250
      microM). In conclusion, these findings support the concept that NO induces
      suppression of cell-mediated immune responses by selective action on Th1 T cells,
      thereby promoting a Th2 response.

PMID- 16642465
TI  - Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects
      and induction of immune accessory molecules by interferon-gamma.
AB  - Cytokine-induced killer cells (CIK cells), coexpressing CD3 and CD56, can be
      expanded from peripheral blood mononuclear cells by the timed addition of
      interferon-gamma (IFN-gamma), IL-2 and OKT3. The effects of CIK cells on primary,
      autologous CLL cells are described. We used MACS to separate CD3(+) cells for
      expansion of CIK cell effectors and CD19(+) targets from peripheral blood of 16
      CLL patients. Apoptosis was assessed by measuring annexinV staining in CLL cells.
      After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was
      15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK
      cells resulted in an increased ICAM-1 expression on CLL cells and an increase in
      apoptosis of CLL targets (30%). These effects were mediated by IFN-gamma
      secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells
      secrete IFN-gamma that modulates the expression of adhesion molecules on CLL
      cells, and this enhances apoptosis induction by cytotoxic effector cells.

PMID- 16642466
TI  - Dietary fiber intake and subsequent risk of colorectal cancer: the Japan Public
      Health Center-based prospective study.
AB  - Results on the association of dietary fiber intake with colorectal cancer risk
      were inconsistent among previous large prospective studies, but studies in non
      Western populations are lacking. Consequently, the authors investigated the
      association between dietary fiber intake and the subsequent risk of colorectal
      cancer in a prospective cohort study of a Japanese population. Dietary fiber
      intake was estimated from food-frequency questionnaires comprising 44 or 52 items
      at the baseline survey and 138 food items at a 5-year follow-up survey. The
      authors identified 907 cases of colorectal adenocarcinoma diagnosed
      pathologically in 86,412 subjects during a 10-year follow-up from the baseline
      survey. After the 5-year follow-up survey, 522 cases were identified in 78,326
      subjects during a 5.8-year follow-up. The authors estimated the multivariate
      adjusted hazard ratios of colorectal cancer for dietary fiber intake using Cox's
      proportional hazards model. The authors found no statistically significant
      association between dietary fiber intake and colorectal cancer in analyses using
      data either from the baseline survey or from the 5-year follow-up survey.
      However, the risk of only the lowest quintile was high, compared with the second
      to the fifth quintiles. Furthermore, the lowest subtertile in the lowest quintile
      was associated with an increased risk in women (hazard ratio(Sub1 vs. Q5), 2.3;
      95% confidence interval, 1.0-5.2). In conclusion, although a minor effect cannot
      be ruled out, the results did not support a hypothesis of a dose-dependent
      protective effect of dietary fiber intake against colorectal cancer.

PMID- 16642467
TI  - Radon, secondhand smoke, glutathione-S-transferase M1 and lung cancer among
      women.
AB  - Tobacco smoke and ionizing radiation induce oxidative stress by transmitting or
      generating reactive oxygen species (ROS). We hypothesized that glutathione-S
      transferase M1 (GSTM1) null homozygotes would have decreased ability to
      neutralize ROS that might increase their susceptibility to lung cancer. A case
      only design was used with lung cancer cases pooled from 3 previously completed
      case-control studies using archival tissue samples from 270 lung cancer cases to
      genotype GSTM1. Radon concentrations were measured with long-term alpha-track
      radon detectors. Secondhand smoke (SHS) was measured with questionnaires and
      interviews. Unconditional logistic regression was used to calculate the
      interaction odds ratios (OR) and 95% confidence intervals (95% CI). Radon
      concentrations >121 Bq m(-3) were associated with a >3-fold interaction OR (OR =
      3.41; 95% CI = 1.10, 10.61) for GSTM1 null homozygotes compared to GSTM1
      carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1
      interaction OR was also elevated (OR = 2.28; 95% CI = 1.15-4.51) among never
      smokers. This may be the first study to provide evidence of a GSTM1 and radon
      interaction in risk of lung cancer. Additionally, these findings support the
      hypothesis that radon and SHS promote neoplasia through shared elements of a
      common pathway.

PMID- 16642468
TI  - Family history of breast cancer and short-term effects of childbirths on breast
      cancer risk.
AB  - The long-term protective effect of a pregnancy on breast cancer risk is preceded
      by a short-term adverse effect, possibly reflecting a promoting effect of
      pregnancy hormones. In the present study, we explore whether a family history of
      breast cancer modifies time-related effects of pregnancies, with special emphasis
      on the transient increase in risk of breast cancer shortly after birth. Our study
      cohort comprises 1,067,289 Norwegian women aged 20-74 years. The mean follow-up
      time was 18 years. Incidence rate ratios were estimated by Poisson regression
      analyses of person-years at risk. Of the 7,377 women diagnosed with breast cancer
      during follow-up, a total of 828 (11%) had a mother or a sister with breast
      cancer diagnosis. Women with a family history of breast cancer had a 2-3-fold
      higher risk of breast cancer than did women without any affected family member,
      highest for those with a relative diagnosed before they were 50 years. Similar to
      women without a familial excess risk, increasing parity was associated with an
      overall protective effect among women with a familial predisposition, regardless
      of age at diagnosis of the relative. Whereas women with no familial excess risk
      experienced a transient increase in risk mainly after late age births, women with
      a family history of breast cancer experienced an adverse effect of pregnancies
      also at younger ages. The present results give further support to the hypothesis
      that the adverse effect of a term birth can be explained by a promoting effect of
      pregnancy hormones.

PMID- 16642469
TI  - Hereditary cancer predisposition in children: genetic basis and clinical
      implications.
AB  - Although cancer predisposition syndromes are rare and malignancies arising in
      this context account for only 1-10% of childhood tumors, studies performed in
      affected patients and their families have been of unique value for the
      understanding of cancer development. Three classes of genes (tumor suppressor
      genes, oncogenes and stability genes) have been identified and shown to be
      involved in the pathogenesis of familial, as well as sporadic tumors. Cancer has
      long been recognized as a genetic disease of somatic cells. Despite improved
      understanding of the molecular basis of predisposition to cancer and better
      diagnostic tools, the care of these patients and their families remains a major
      challenge for the clinician. Medical, psychological, ethical and legal issues
      have to be considered. This review focuses on examples of each class of inherited
      cancer predisposition syndromes with special implications for patients in the
      pediatric age group, including retinoblastoma predisposition, Li-Fraumeni
      syndrome, multiple endocrine neoplasia disorders and Fanconi anemia. The genetic
      basis of cancer predisposition is discussed as well as the major concepts and
      controversies in the clinical management of these patients and their families.

PMID- 16642470
TI  - Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through
      fibroblast growth factor-2 response element and homeodomain protein-binding site
      in the proximal promoter of the BSP gene.
AB  - Insulin-like growth factor-I (IGF-I) promotes bone formation by stimulating
      proliferation and differentiation of osteoblasts. Bone sialoprotein (BSP), is
      thought to function in the initial mineralization of bone, is selectively
      expressed by differentiated osteoblast. To determine the molecular mechanism of
      IGF-I regulation of osteogenesis, we analyzed the effects of IGF-I on the
      expression of BSP in osteoblast-like Saos2 and in rat stromal bone marrow (RBMC
      D8) cells. IGF-I (50 ng/ml) increased BSP mRNA levels at 12 h in Saos2 cells. In
      RBMC-D8 cells, IGF-I increased BSP mRNA levels at 3 h. From transient
      transfection assays, a twofold increase in transcription by IGF-I was observed at
      12 h in pLUC3 construct that included the promoter sequence from -116 to +60.
      Effect of IGF-I was abrogated by 2-bp mutations in either the FGF2 response
      element (FRE) or homeodomain protein-binding site (HOX). Gel shift analyses
      showed that IGF-I increased binding of nuclear proteins to the FRE and HOX
      elements. Notably, the HOX-protein complex was supershifted by Smad1 antibody,
      while the FRE-protein complex was shifted by Smad1 and Cbfa1 antibodies. Dlx2 and
      Dlx5 antibodies disrupted the formation of the FRE- and HOX-protein complexes.
      The IGF-I effects on the formation of FRE-protein complexes were abolished by
      tyrosine kinase inhibitor herbimycin A (HA), PI3-kinase/Akt inhibitor LY249002,
      and MAP kinase kinase inhibitor U0126, while IGF-I effects on HOX-protein
      complexes were abolished by HA and LY249002. These studies demonstrate that IGF-I
      stimulates BSP transcription by targeting the FRE and HOX elements in the
      proximal promoter of BSP gene.

PMID- 16642471
TI  - Increased expression of glycosyl-phosphatidylinositol anchor attachment protein 1
      (GPAA1) is associated with gene amplification in hepatocellular carcinoma.
AB  - Glycosyl-phosphatidylinositol (GPI) anchor attachment protein 1 (GPAA1)
      transcript level was frequently up-regulated in our earlier study on gene
      expression profile. We therefore analyzed the potential involvement of GPAA1 in
      hepatocellular carcinoma (HCC) as GPAA1 gene locates at chromosome 8q24.3 which
      chromosome region is frequently amplified in HCCs. In this study, we observed
      that GPAA1 transcript in the HCCs (n = 93) showed a significantly higher
      expression level compared with their paralleled adjacent nontumor liver tissues,
      cirrhosis (n = 15) and normal (n = 16) liver tissues using real-time quantitative
      RT-PCR (p < 0.005). We also demonstrated that GPAA1 protein up-regulation was
      common in HCCs (90%, 9/10), and GPAA1 gene was frequently amplified (73%, 11/15)
      using quantitative microsatellite analysis. Increased GPAA1 expression was
      significantly associated with HCCs poor cellular differentiation (p = 0.011) and
      poor prognosis (p = 0.010). We then modulated the GPAA1 expression level in HCC
      cells (Hep3B) by transfection experiments, which was shown to positively regulate
      cell adhesion ability (p = 0.004) and proliferation rate (p = 0.037). Our data
      revealed GPAA1 gene amplification with overexpression of RNA and protein in HCC.
      GPAA1 is a potential amplification target of chromosome 8q and responsible to
      regulate tumor cells behavior.

PMID- 16642472
TI  - Silencing of the UCHL1 gene in human colorectal and ovarian cancers.
AB  - Aberrant DNA methylation is associated with many types of human cancers. To
      identify genes silenced in human colorectal cancers, we performed a microarray
      analysis for genes whose expression was induced by treatment of HCT116 human
      colon cancer cells with a demethylating agent, 5-aza-2'-deoxycitidine (5-aza-dC).
      Seven known genes were identified as being upregulated (> or =8-fold) and
      expressed at more than twice as high as the average level. Among these was the
      UCHL1 gene (also known as PGP9.5), which is involved in regulation of cellular
      ubiquitin levels. A dense CpG island in its promoter region was completely
      methylated in HCT116 cells, and no mRNA was detected. 5-Aza-dC treatment of
      HCT116 cells induced dose-dependent demethylation of the CpG island, and restored
      UCHL1 mRNA and protein expression. UCHL1 silencing was observed in 11 of 12 human
      colorectal cancer cell lines, and its methylation was detected in 8 of 17 primary
      colorectal cancers. Further, UCHL1 silencing was observed in 6 of 13 ovarian
      cancer cell lines, and its methylation was detected in 1 of 17 primary ovarian
      cancers. These results showed that UCHL1 is inactivated in human colorectal and
      ovarian cancers by its promoter methylation, and suggest that disturbance of
      cellular ubiquitin levels is present.

PMID- 16642473
TI  - Frequent gene dosage alterations in stromal cells of epithelial ovarian
      carcinomas.
AB  - Stromal cells are an active and integral part of epithelial neoplasms. We have
      previously observed allelic imbalance on chromosome 3p21 in both stromal and
      epithelial cells of ovarian tumors. This study was designed to explore gene
      dosage alterations throughout human chromosomes from stromal and epithelial cells
      of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples,
      microdissected from epithelial ovarian carcinomas, were analyzed using multiplex
      ligation-dependent probe amplification technique. Analysis covered 110 cancer
      related genes. Frequent genetic alterations were detected both in the stroma and
      epithelium of ovarian carcinomas. The mean number of altered genes per tumor was
      10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains
      was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of
      changes associated with advanced tumor stage (p = 0.035) and death due to ovarian
      cancer (p = 0.032). The most frequent alteration was the deletion of the deleted
      in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of
      DCC was related to endometrioid subtype (p = 0.033). Large chromosomal
      aberrations were detected on the basis of alterations in adjacent genes. Most
      importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss)
      in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic
      alterations in stromal cells of epithelial ovarian carcinomas resembled those of
      malignant epithelial cells and may indicate a common precursor cell type.
      Epithelial-mesenchymal transition may generate transformed cancer cells and
      modify the tumor microenvironment with distinct properties.

PMID- 16642474
TI  - Interleukin-6 induces both cell growth and VEGF production in malignant
      mesotheliomas.
AB  - Malignant mesothelioma (MM), an incurable tumor, is reportedly an interleukin-6
      (IL-6) secreting tumor. The pathological significance of IL-6 overexpression in
      this tumor, however, has remained unclear. We investigated the biological
      functions of IL-6 in mesotheliomas. Five mesothelioma cell lines were analyzed
      for IL-6 production and IL-6 receptor (IL-6R) expression. Of them, 2 produced
      high levels of IL-6, 2 produced intermediate levels and 1 cell line showed no
      secretion. All mesothelioma cell lines used in this study expressed very small
      amounts of IL-6R mRNA. We compensated for this low level of IL-6R expression in
      mesotheliomas by adding recombinant soluble IL-6R (sIL-6R) to mediate the IL-6
      signal. IL-6 together with sIL-6R was found to promote cell growth of H2052 and
      H226 MMs classified as high-level IL-6 producers in a dose-dependent manner.
      Moreover, a humanized anti-IL-6R antibody (MRA) capable of blocking IL-6
      signaling suppressed the cell growth of mesotheliomas induced by IL-6/sIL-6R.
      These findings demonstrate that IL-6 serves as an autocrine growth factor in the
      development of mesothelioma. In addition, IL-6/sIL-6R stimulation increased the
      expression of vascular endothelial growth factor (VEGF) in 4 out of 5 cell lines,
      and this induction was inhibited by MRA treatment. The involvement of the signal
      transducer and activator of transcription 3 (STAT3) pathway in both cell growth
      and VEGF induction by IL-6/sIL-6R was verified by dominant negative STAT3
      transduction combined with adenovirus gene-delivery methods. Although IL-6
      induces VEGF through the JAK2/STAT3 pathway, anti-VEGF antibody could not inhibit
      the IL-6-induced cell growth observed in H2052 and H226. We concluded that IL-6
      dependent growth does not occur via VEGF induction. These results suggest that
      treatment with anti-IL-6R antibody may constitute a potential molecular targeting
      therapy for MMs.

PMID- 16642475
TI  - Outgrowth of human liver metastases after resection of the primary colorectal
      tumor: a shift in the balance between apoptosis and proliferation.
AB  - Rapid outgrowth of metastases after removal of the primary tumor has been
      described in several mouse models. Loss of primary tumor-induced inhibition of
      angiogenesis in the metastases has been suggested as the underlying cause.
      Accordingly, we recently demonstrated that vascular density in human colorectal
      liver metastases increases after primary tumor resection. Here, we investigate
      whether this increase in vascular density has, in its turn, effects on the tumor
      growth of the liver metastases. We analyzed tumor growth in synchronous liver
      metastases from patients with the primary tumor in place, in synchronous
      metastases from patients with the primary tumor resected and in metachronous
      metastases. Tumor growth was studied by assessing the percentage of cells
      undergoing apoptosis by activated caspase-3 staining, and the percentage of
      proliferating cells by Ki-67 staining. While the percentage of proliferating
      cells within the metastases showed a modest increase after primary tumor
      resection, a significant decrease in the percentage of apoptotic cells was
      observed. Taken together, an increased net tumor growth of the metastases
      occurred after primary tumor resection. This acceleration of tumor growth could
      be confirmed by studying biopsies taken from the same patient before and after
      tumor resection. Our data show that in human cancer patients, a primary tumor may
      inhibit the growth of its liver metastases.

PMID- 16642476
TI  - Frequent EGFR mutations in brain metastases of lung adenocarcinoma.
AB  - Lung adenocarcinomas often metastasize to the brain, and the prognosis of
      patients with brain metastases is still very poor. The epidermal growth factor
      receptor (EGFR) gene is mutated in a considerable fraction of primary lung
      adenocarcinomas, in particular those with drastic response to EGFR tyrosine
      kinase inhibitors. The present study was designed to elucidate the prevalence of
      EGFR mutations in brain metastases and the timing of their occurrence during
      cancer progression. EGFR mutations were detected in 12 of 19 metastatic lung
      adenocarcinomas to the brain (63%). This frequency was higher than those in
      previous studies for EGFR mutations at various stages of lung adenocarcinoma in
      East Asia, including Japan (i.e., 20-55%). In 6 cases with EGFR mutations, the
      corresponding primary lung tumors were also examined for the mutations, and in
      all of them, the same types of EGFR mutations were detected also in the primary
      tumors. In 2 of them, second metastatic brain tumors in addition to the first
      ones were also available for analysis, and the same types of EGFR mutations were
      detected in both the first and second ones in both cases. These results indicate
      that EGFR mutations are present frequently in brain metastases and occur
      preceding brain metastasis. These findings will be highly informative for
      treatment of metastatic lung adenocarcinoma to the brain.

PMID- 16642477
TI  - Genetic aberrations in prostate cancer by microarray analysis.
AB  - The aim of this study was to screen genetic as well as expression alterations in
      prostate cancer. Array comparative genomic hybridization (aCGH) to a 16K cDNA
      microarray was performed to analyze DNA sequence copy number alterations in 5
      prostate cancer cell lines and 13 xenografts. The aCGH confirmed the previously
      implicated common gains and losses, such as gains at 1q, 7, 8q, 16p and 17q and
      losses at 2q, 4p/q, 6q, 8p, 13q, 16q, 17p and 18q, which have previously been
      identified by chromosomal CGH (cCGH). Because of the higher resolution of aCGH,
      the minimal commonly altered regions were significantly narrowed-down. For
      example, the gain of 8q was mapped to three independent regions, 8q13.3-q21.11,
      8q22.2 and 8q24.13-q24.3. In addition, a novel recurrent gain at 9p13-q21 was
      identified. The concomitant expression analysis indicated that genome-wide DNA
      sequence copy number (gene dosage) was significantly associated with the
      expression level (p < 0.0001). The analyses indicated several individual genes
      whose expression was associated with the gene copy number. For example, gains of
      PTK2 and FZD6, were associated with the increased expression, whereas losses of
      TNFRSF10B (alias DR5) and ITGA4 with decreased expression. In conclusion, the
      aCGH mapping data will aid in the identification of genes altered in prostate
      cancer. The combined expression and copy number analysis suggested that even a
      low-level copy number change may have significant effect on gene expression, and
      thus on the development of prostate cancer.

PMID- 16642478
TI  - Regularly methylated novel pro-apoptotic genes associated with recurrence in
      transitional cell carcinoma of the bladder.
AB  - Epigenetic silencing of tumor suppressor genes by promoter hypermethylation has
      been shown for a variety of genes in bladder cancer. Various p53 target genes
      have been investigated, but only few demonstrated promoter hypermethylation when
      semiquantitative detection methods were applied. To address to the question
      whether promoter methylation of novel p53 effector genes is a common event in
      transitional cell carcinoma of the bladder, we selected the p53 target genes
      apoptotic protein-activating factor (APAF-1), Caspase 8 (CASP-8), death
      associated protein kinase, (DAPK-1) and insulin-like growth-factor-binding
      protein-3 (IGFBP-3), performing quantitative methylation-specific real-time PCR.
      The individual level of methylation (normalized index of methylation) was
      correlated with clinicopathological features as well as the biological behavior
      of the superficial and muscleinvasive tumors. Tissue was obtained from 110 tumor
      patients and 20 patients without urological malignancy. The median follow-up of
      the tumor patients was 52 months. Hypermethylation of the promoter region in
      tumor specimens was common for APAF-1 (100%), DAPK-1 (74%) and IGFBP-3 (66%), but
      not for CASP-8 (3.6%). It was seen less frequently and with undetectable or low
      methylation levels in the normal urothelium group. The APAF-1 methylation levels
      significantly correlated with tumor stage and tumor grade. The APAF-1 and IGFBP-3
      methylation levels were able to separate tumors with higher recurrence risk from
      low-risk tumors in nonmuscleinvasive and muscleinvasive tumors. In multivariate
      analysis, APAF-1 and IGFBP-3 methylation levels were independent prognostic
      markers for recurrence in superficial bladder tumors. This study provides new
      insights into the role of promoter methylation of selected p53 target genes. The
      extent of promoter methylation of specific genes offers additional prognostical
      information and is associated with the outcome in patients with nonmuscleinvasive
      and muscleinvasive bladder cancer.

PMID- 16642479
TI  - High incidence of second basal cell skin cancers.
AB  - We considered the risk of second basal cell cancers (BCC) of the skin using a
      population-based series of 1,868 BCC collected between 1976 and 1985 in the Swiss
      Cantons of Vaud and Neuchatel, and followed-up to the end of 2003. Overall, 507
      second BCC were observed versus 59.98 expected, corresponding to a standardized
      incidence ratio (SIR) of 8.45 (95% CI: 7.73-9.22). The SIRs were similar in men
      and women in subsequent calendar periods, but tended to decline with advancing
      age at diagnosis of first BCC, from 13.98 below age 50 to 7.13 at age 70 or over.
      Consequently, the rate of first BCC increased to approximately 30-fold between
      7/100,000 at age 30-39 and 200/100,000 at age 70-79, but the rate of second BCC
      increased only about 3-fold between 31/1,000 at age 30-39 and 110/1,000 at age 70
      79. The cumulative risk of second BCC was 11% at 5 years, 21% at 10 years and 40%
      at 20 years. This study indicates that the relative (but not the absolute) risk
      of second BCC is greater at younger age and declines with advancing age, and is
      therefore compatible with an excess baseline risk in a population of susceptible
      individuals.

PMID- 16642480
TI  - Targeting constitutive and interleukin-6-inducible signal transducers and
      activators of transcription 3 pathway in head and neck squamous cell carcinoma
      cells by curcumin (diferuloylmethane).
AB  - Numerous reports suggest that interleukin-6 (IL-6) promotes survival and
      proliferation of tumor cells through the phosphorylation of a cell-signaling
      protein, signal-transducer-and-activator-of-transcription-3 (STAT3). Constitutive
      activation of STAT3 in head and neck squamous cell carcinoma (HNSCC) and its role
      in proliferation of this tumor has been demonstrated. Thus, agents that can
      suppress STAT3 activation have potential for the treatment of HNSCC. In the
      present report, we demonstrate that most HNSCC cell lines had constitutively
      active STAT3 and that curcumin (diferuloylmethane), a pharmacologically safe
      agent in humans, inhibited STAT3 phosphorylation in a dose- and time-dependent
      manner. Nuclear translocation of STAT3 was also inhibited by curcumin. The
      inhibition of STAT3 activation by curcumin was reversible, although even 24 hr
      after curcumin removal, only partial reversal occurred. Besides inhibiting
      constitutive expression, curcumin also abrogated the IL-6-induced activation of
      STAT3 in HNSCC cells. When compared with AG490, a well-characterized JAK2
      inhibitor, curcumin was more rapid (30 min vs. 4 hr) and more potent (25 microM
      vs. 100 microM) inhibitor of STAT3 phosphorylation. Curcumin was also a more
      potent inhibitor of HNSCC cell proliferation than AG490. Overall, our results
      demonstrated that curcumin is a potent inhibitor of constitutive and IL-6-induced
      STAT3 phosphorylation. This mechanism may be at least partially responsible for
      curcumin's ability to suppress proliferation of HNSCC cells.

PMID- 16642481
TI  - Development of a membrane array-based multimarker assay for detection of
      circulating cancer cells in patients with non-small cell lung cancer.
AB  - Combination of multiple mRNA markers has been largely investigated for detection
      of circulating cancer cells. However, current PCR-based methods are relatively
      expensive and time consuming. The aim of this study was to develop a membrane
      array-based multimarker assay for detection of circulating cancer cells in
      nonsmall cell lung cancer (NSCLC) patients. At first, we selected 22 candidate
      genes by means of suppression subtractive hybridization and Northern blot
      analysis. The diagnostic value of each candidate gene was then preliminarily
      evaluated in 50 pairs of blood samples by membrane array method. Accordingly, 17
      genes with area under the ROC curve (AUC) > or = 0.8 were selected as target
      genes to reconstruct the diagnostic membrane array, which was then used to test
      peripheral blood samples from 100 NSCLC patients and 147 control subjects. ROC
      curve analysis demonstrated that the optimal threshold number of overexpressed
      markers on membrane array for discrimination between NSCLC patients and control
      subjects was 12. As a result, the diagnostic membrane array could detect
      circulating cancer cells in 90 (90%) of 100 NSCLC patients and in 14 (9.5%) of
      147 control subjects (including 6 of 100 normal persons, 3 of 20 breast cancer
      patients, 3 of 15 colorectal cancer patients and 2 of 12 gastric cancer
      patients). Moreover, the detection rate was significantly correlated with NSCLC
      patients' metastatic status and overall stage (p = 0.028 and 0.014,
      respectively). These results suggested that our blood-based membrane array assay
      for molecular detection of circulating lung cancer cells has great potential for
      clinical applications.

PMID- 16642482
TI  - Self-reported goiter is associated with a significantly increased risk of gastric
      noncardia adenocarcinoma in a large population-based Chinese cohort.
AB  - Iodine is concentrated by the gastric mucosa, where it may act as an antioxidant.
      Therefore, iodine deficiency, and its sequelae goiter, may be associated with an
      increased risk of gastric cancer. We examined the association between self
      reported goiter and upper gastrointestinal cancer in a Chinese cohort of 29,584
      adults. Using multivariate adjusted Cox models, we found goiter associated with a
      significantly increased risk of gastric noncardia adenocarcinoma, HR (95% CI)
      2.04 (1.01, 4.11) and nonsignificantly with gastric cardia adenocarcinoma, HR
      (95% CI) 1.45 (0.91, 2.30). We also found a borderline, insignificant increased
      risk of esophageal squamous cell carcinoma, HR (95% CI) 1.37 (0.97, 1.94). Our
      findings are consistent with the hypothesis that iodine deficiency is associated
      with an increased risk of gastric cancer.

PMID- 16642483
TI  - Evaluation of pediatric oncology patients with previous multiple central
      catheters for vascular access: is Doppler ultrasound needed?
AB  - BACKGROUND/PURPOSE: Pediatric oncology patients who have undergone placement of
      multiple central venous catheters may have thrombosis or stenosis in the upper
      venous system. The purpose of this study was to identify factors that predict
      venous thrombosis or stenosis and to evaluate the role of Doppler ultrasonography
      in assessing the upper venous system of pediatric patients requiring multiple
      central vascular catheters. METHODS: The medical records of eligible patients
      were reviewed with regard to demographics, primary disease, type of catheter,
      duration of previous central venous access, association with infection, operative
      notes, and Doppler ultrasonographic findings. RESULTS: Our evaluation criteria
      were met in 50 cases (47 patients). In 10 cases, Doppler ultrasonography revealed
      abnormality in the upper venous system. Patient demographics, primary disease,
      type of catheter, duration of previous central venous access, or association with
      infection were not found to significantly predict the abnormality in the upper
      venous system. Placement of central venous access device was performed without
      difficulty when the site of placement was chosen on the basis of ultrasonographic
      findings. CONCLUSION: Doppler ultrasonography is useful in diagnosing thrombosis
      or stenosis in asymptomatic pediatric patients requiring placement of multiple
      central venous catheters.

PMID- 16642484
TI  - Comparison of treatment outcomes of childhood Hodgkin lymphoma in two US centers
      and a center in Recife, Brazil.
AB  - BACKGROUND: Pediatric Hodgkin lymphoma (HL) has a cure rate of more than 80% in
      high-income countries (HIC). However, more than 80% of the world's children live
      in low-income countries (LIC), where the cure rate is often much lower.
      PROCEDURE: We compared the outcome of HL of 371 patients treated at two pediatric
      oncology centers in the US to that of 62 patients treated at one center in
      Recife, Brazil (IMIP) to determine whether the same treatment strategy should be
      used in both high-income and LIC. The logrank test was used to compare event-free
      and overall survival. RESULTS: The percentages of patients with unfavorable
      disease at each center were similar (P = 0.72). Patients with favorable disease
      at IMIP had estimated 5-year survival rates comparable to those of the US centers
      (100% and 99%, respectively). Among patients with unfavorable disease, those
      treated at IMIP had a 5-year event-free survival (EFS) rate of 60%, compared to
      78% at the US centers; (P = 0.08). The 5-year survival estimate after relapse was
      25% at IMIP versus 61% at the US centers (P = 0.08). The 5-year overall survival
      for patients with unfavorable disease was 72% at IMIP versus 90% at the US
      centers (P = 0.01). CONCLUSIONS: Intensive frontline therapy should be considered
      for patients with unfavorable HL in LIC where the relapse rate is high and the
      salvage rate is low, provided that supportive care is adequate.

PMID- 16642485
TI  - Binding diversity of the two binding sites of ricin B lectin.
AB  - Ricin B is a galactose-binding protein, which contains two binding sites. We have
      compared the binding properties of the two binding sites of ricin B chain toward
      different mono- and disaccharide ligands. The free energies of binding are
      calculated using the free energy perturbation simulation (thermodynamic
      integration method) and linear interaction energy approach using CHARMM force
      field. The second binding site of the protein was found to be weaker compared to
      the first. The details of the hydrogen-bonding scheme suggested the origin of the
      epimeric specificity of the protein. The reason for the weaker binding capacity
      of the second binding site has been addressed.

PMID- 16642487
TI  - Pre-transplant minimal residual disease in children with acute lymphoblastic
      leukemia.

PMID- 16642488
TI  - Identification of a novel MYH9 mutation in a patient with May-Hegglin anomaly.

PMID- 16642489
TI  - Effect of race on outcome of white and black children with acute myeloid
      leukemia: the St. Jude experience.
AB  - BACKGROUND: The association between race and outcome of treatment for childhood
      acute myeloid leukemia (AML) has not been adequately studied. PROCEDURE: We
      compared the clinical characteristics, biological features, and outcomes between
      white and black children with AML who were treated on five consecutive clinical
      protocols (1980-2002) at St. Jude Children's Research Hospital. We used
      proportional hazards modeling to investigate the relation between race and
      outcome. RESULTS: We observed no statistically significant differences between
      the 229 white and 58 black patients in clinical characteristics, FAB subtype,
      cytogenetic features, or outcome. There were no significant differences in event
      free survival (EFS) or overall survival (OS) between the two race groups in
      individual clinical trials or in all studies combined. For the study group as a
      whole, the 5-year survival estimate was 39.2% +/- 3.6% for white patients and
      33.8% +/- 6.5% for black patients. However, on our most recent trial (AML-97),
      there was a trend towards inferior outcome among black patients: the 5-year
      survival estimates were 55.6% +/- 12.3% and 27.3% +/- 13.5% for whites and
      blacks, respectively. CONCLUSIONS: Although we detected no differences in
      treatment outcome between white and black children with AML over the entire study
      period, black children appear to have worse outcomes than white children during
      more recent studies. Improved treatment is needed for all children with AML.

PMID- 16642490
TI  - Treatment late effects in long-term survivors of pediatric sarcoma.
AB  - PURPOSE: To assess health and musculoskeletal function in survivors of pediatric
      sarcomas. PATIENTS AND METHODS: Thirty-two individuals treated for Ewing sarcoma
      family of tumors (ESFT), rhabdomyosarcoma (RMS), or non-rhabdomyosarcoma soft
      tissue sarcomas (NR-STS) with multi-modality therapy were enrolled on this cross
      sectional study. Median age at the time of therapy was 15.4 years (range 7.1
      34.2), median age at the time of analysis was 37.4 years (17.5-55.4), and median
      duration of time elapsed from completion of therapy was 17.3 years (2.9-32.6).
      Participants underwent assessments of musculoskeletal functioning, cardiac
      function, metabolic and lipid analyses, renal and gonadal function, and
      psychological evaluation. RESULTS: This cohort of sarcoma survivors shows
      expected locoregional limitations in function of the area affected by sarcoma,
      and impaired global musculoskeletal functioning as evidenced by limited endurance
      and limited overall activity levels. The cohort also demonstrated substantial
      rates of cardiac dysfunction, elevated body fat index, hyperlipidemia, chronic
      psychological distress, and infertility in men (76%) and premature menopause
      (49%) in women. CONCLUSION: Sarcoma survivors demonstrate diminished locoregional
      and global musculoskeletal functioning which likely limit occupational
      opportunities and socioeconomic health. In addition, the combination of
      diminished cardiac reserve, limited activity levels, and lipid dysregulation in
      sarcoma survivors suggests that this population is at increased risk for
      cardiovascular disease, even many years following completion of sarcoma therapy.
      Sarcoma survivors may benefit from life long follow-up for cardiovascular disease
      and from occupational counseling upon completion of therapy.

PMID- 16642491
TI  - Enantiomer separation of amino acids in immunoaffinity micro LC-MS.
AB  - Chiral immunoaffinity microbore columns were directly interfaced with MS
      detection, and the effect of column length and temperature on the enantiomer
      separation of a number of underivatized aromatic and aliphatic amino acids was
      investigated utilizing an antibody chiral stationary phase that had been prepared
      by immobilizing a monoclonal anti-D-amino acid antibody onto silica. The stronger
      affinity of the antibody towards aromatic and bulky amino acids allowed
      separation of such analytes in a 0.75 x 150 mm column, while an increase in
      column length enabled separation of more weakly bound compounds. The strength of
      interaction between chiral selector and analytes could be modulated conveniently
      by lowering the temperature. For the first time, simultaneous enantiomer
      separation of mixtures of amino acids was achieved on antibody-based chiral
      stationary phases using extracted ion chromatograms.

PMID- 16642492
TI  - Enantioselective 2-hydroxylation of RS-8359, a selective and reversible MAO-A
      inhibitor, by cytochrome P450 in mouse and rat liver microsomes.
AB  - RS-8359, (+/-)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[d]
      pyrimidine is a racemic compound with a selective and reversible monoamine
      oxidase A (MAO-A) inhibition activity. The substrate and product
      enantioselectivity with respect to 2-hydroxylation of RS-8359 enantiomers was
      studied using mouse and rat liver microsomes. In mice, the (S)-enantiomer was
      transformed to the cis-diol metabolite, whereas the (R)-enantiomer to the trans
      diol metabolite. The Vmax/Km value for the formation of the cis-diol metabolite
      from the (S)-enantiomer was sevenfold greater than that for the formation of the
      trans-diol metabolite from the (R)-enantiomer. The greater Vmax/Km value for the
      (S)-enantiomer was due to the tenfold smaller Km value compared to that for the
      (R)-enantiomer. The results were in fair agreement with the previously reported
      low plasma concentrations of the (S)-enantiomer and the high recovery of the cis
      diol metabolite derived from the (S)-enantiomer in urine after oral
      administration of RS-8359 to mice. Similarly to mice, in rats the (R)-enantiomer
      was transformed to the trans-diol metabolite, whereas the (S)-enantiomer yielded
      the cis-diol and trans-diol metabolites. The Vmax/Km value for the (R)-enantiomer
      was larger than that for the (S)-enantiomer in rats, indicating that the low
      plasma concentration of the (S)-enantiomer in rats might be caused by a metabolic
      reaction other than P450-dependent hydroxylation. CYP3A was shown to be
      responsible for the trans-diol formation from the (R)-enantiomer.

PMID- 16642493
TI  - Fast and precise access to enantiomerization rate constants in dynamic
      chromatography.
AB  - An analytical solution of the unified equation to evaluate elution profiles of
      interconverting enantiomers in dynamic chromatography is presented. Rate
      constants k1 and k(-1) and Gibbs activation energies are directly obtained from
      the chromatographic parameters (retention times tR A and tR A of the
      interconverting enantiomers, the peak widths at half height wA and wB, and the
      relative plateau height hp), and the initial amounts A0 and B0 of the enantiomers
      without any iterative and time consuming computational step. Therefore, this
      equation is no longer limited to racemic analytes. The analytical solution
      presented here was validated by comparison with a dataset of 125,000 simulated
      elution profiles of enantiomerizations. Furthermore, it was found that the
      recovery rate from a defined dataset is on average 40% higher using the unified
      equation compared to evaluation methods based on iterative computer simulation.
      The new equation was applied to determine the enantiomerization rate constant of
      1-n-butyl-2-tert-butyldiaziridine by enantioselective gas chromatography. The
      activation parameters (DeltaH(double dagger) = 112.6 +/- 2.5 kJ/mol and
      DeltaS(double dagger) = -27 +/- 2 J/(K mol) were obtained from temperature
      dependent measurements between 100 degrees C and 140 degrees C in 10K steps.

PMID- 16642494
TI  - Enantioselective addition of diethylzinc to aldehydes catalyzed by titanium(IV)
      complexes of N-sulfonylated beta-amino alcohols with four stereogenic centers.
AB  - An N-sulfonylated beta-amino alcohol (R,S,S,R)-9 with four stereogenic centers is
      prepared. The titanium complex of 9 is an effective catalyst to induce excellent
      enantioselectivities for diethylzinc addition to aromatic aldehydes with ee
      values up to 99%. The feature of doubling the quantity of Ti(O-i-Pr)4 required
      relative to the catalytic system of the Ti complex of bidentate N-sulfonylated
      beta-amino alcohols suggests that the two N-sulfonylated beta-amino alcohol
      moieties in 9 behave as two independent bidentate ligands in the catalytic
      system. The results obtained using ligand 15 having one N-sulfonylated beta-amino
      alcohol blocked support the argument of two independent active bidentate moieties
      in 9.

PMID- 16642495
TI  - Enantiomer separation of 1,4-sulfanylalcohols by conventional and low-temperature
      gas chromatography.
AB  - Since 1990, the family of organosulfur molecules has assumed increasing
      importance in pheromone, flavour, and fragrance chemistry. Depending on the
      constitution of the functional groups, various volatile sulfur-containing
      compounds are chiral. However, hitherto it has been impossible to study the
      chirality of 1,4-sulfanylalcohols, since no adequate enantioselective analytical
      technique has been available. Here we report on the enantiomer separation of ten
      volatile 1,4-sulfanylalcohol homologues by applying an heptakis(6-O-tert
      butyldimethylsilyl-2,3-di-O-methyl)-beta-cyclodextrin phase, involving in some
      cases the use of a low-temperature gas chromatographic (ltGC) technique. The
      results are expected to open research potential on the asymmetry of volatile
      organosulfur molecules, particularly in the fields of pheromone, flavour, and
      fragrance research.

PMID- 16642496
TI  - Enthalpy change on mixing a couple of S- and R-enantiomers of some chiral
      compounds at 298.15 K.
AB  - Enthalpy change on the mixing of R- and S-enantiomers of chiral liquid compounds
      such as dimethyl malate (1), methyl 3-hydroxylbutanoate (2), 2-butanol (3), ethyl
      4-chloro-3-hydroxylbutanoate (4), 1,3,3-trimethylbicycle-[2.2.1]heptan-2-one (5),
      3,7-dimethyl-6-octenal (6), and 8-bromo-2,6-dimethyl-2-octene (7) is measured
      over the entire range of mole fractions at 298.15 K, albeit very small values.
      The mixing of chiral liquids of R-1 + S-1, R-2 + S-2, R-3 + S-3, R-6 + S-6, and R
      7 + S-7 produces enthalpic destabilization over the entire range of mole
      fractions, while that of R-4 + S-4 and R-5 + S-5 shows enthalpic stabilization
      over entire compositions. Enthalpy change on mixing at an equimolar concentration
      and the intermolecular interaction obtained by the molecular mechanics
      calculations show a linear correlation, except for a few compounds measured.

PMID- 16642497
TI  - Chiral separation of rac-Ornidazole and detection of the impurity of (R)
      Ornidazole in (S)-Ornidazole injection and raw material.
AB  - (S)-Ornidazole is a subject of research as an antifertility agent in male animals
      at present. However, there seems to be no relative report on chiral separation
      for rac-Ornidazole, which has been used as an effective medicine for more than 30
      years. In this article, the chiral separation of rac-Ornidazole on a Chiralcel OB
      H column based on normal-phase high-performance liquid chromatography (NP-HPLC)
      is investigated and the methodology for detection of impurity of (R)-Ornidazole
      in (S)-Ornidazole injection and raw material is established. The novel mobile
      phase is utilized by mixing n-hexane, methanol and isopropyl alcohol (95:4:1,
      v/v/v) instead of the typical mobile phase of n-hexane and isopropyl alcohol,
      although the methanol, which offers a good resolution factor for the enantiomeric
      separation in this system, is not recommended on the Chiralcel OB-H column
      according to the instruction supplied by Daicel Chemical Ind., LTD (Japan).

PMID- 16642498
TI  - Asymmetric aziridination of 1,3-dienes catalyzed by bisoxazoline-copper
      complexes.
AB  - The asymmetric aziridination of 1,3-dienes catalyzed by bisoxazoline-CuOTf
      complexes with PhI=NTs as a nitrene precursor has been achieved in moderate
      yields with up to >99:1 regioselectivity, up to >99% diastereoselectivity, and up
      to 80% enantioselectivity. alpha,beta,gamma,delta-Unsaturated ketones usually
      produced cis-gamma,delta-aziridinated products, while 1,4-diphenyl-1,3-butadiene
      afforded both of cis- and trans-aziridine derivatives as major products by the
      use of different bisoxazoline ligands. The configuration of cis-aziridine
      derivatives was proposed on the basis of the reaction mechanism.

PMID- 16642499
TI  - Brain 1H magnetic resonance spectroscopic differences in myotonic dystrophy type
      2 and type 1.
AB  - To evaluate cerebral metabolism and intergroup differences in closely matched
      patients with myotonic dystrophy type 2 (DM2, n = 15) and type 1 (DM1, n = 14),
      we performed (1)H magnetic resonance spectroscopic (MRS) analyses of the
      occipital and temporoparietal cortical regions as well as of subcortical frontal
      white matter. Relative to healthy subjects, the concentration of N
      acetylaspartate was significantly reduced in all tested brain regions in both
      disease groups. In the DM1 patients we also observed a concomitant depletion of
      creatine and choline levels, particularly in the frontal white matter. A
      discriminant analysis based on the (1)H-MRS data distinguished between the DM2,
      DM1, and control groups with an overall accuracy of 88%. (1)H-MRS indicates that
      neurochemical alterations involving gray and white matter occur in patients with
      DM2 and DM1. Although structural abnormalities (cerebral atrophy, white matter
      lesions) are similar in DM2 and DM1, changes in cerebral metabolites can
      differentiate these disease groups, suggesting that the diseases differ in their
      neurocellular pathology.

PMID- 16642500
TI  - Concentric-needle single-fiber electromyography for the diagnosis of myasthenia
      gravis.
AB  - The goal of this study was to estimate the accuracy of concentric-needle single
      fiber electromyography (CN-SFEMG) for the diagnosis of myasthenia gravis (MG). A
      consecutive series of patients referred for CN-SFEMG was evaluated by an
      investigator blinded to the results of CN-SFEMG in order to determine the
      presence or absence of MG using an independent reference standard. Sensitivity,
      specificity, predictive values, and likelihood ratios were calculated. The study
      population included 51 patients (21 with MG). CN-SFEMG was normal in 34 patients
      (67%) and abnormal in 17 (33%). The sensitivity of CN-SFEMG for the diagnosis of
      MG was 0.67 and the specificity was 0.96. The positive likelihood ratio was 16.8
      and the negative likelihood ratio was 0.34. The positive and negative predictive
      values were 0.93 and 0.76, respectively. These results indicate that CN-SFEMG
      showing abnormal jiggle is extremely useful for confirming the diagnosis of MG,
      but that CN-SFEMG showing normal jiggle has limited utility in excluding the
      diagnosis.

PMID- 16642501
TI  - Mitochondrial dysfunction in amyotrophic lateral sclerosis also affects skeletal
      muscle.

PMID- 16642502
TI  - Cofactor assisted gating mechanism in the active site of NADH oxidase from
      Thermus thermophilus.
AB  - NADH oxidase (NOX) from Thermus thermophilus is a member of a structurally
      homologous flavoprotein family of nitroreductases and flavin reductases. The
      importance of local conformational dynamics in the active site of NOX has been
      recently demonstrated. The enzyme activity was increased by 250% in the presence
      of 1 M urea with no apparent perturbation of the native structure of the protein.
      The present in silico results correlate with the in vitro data and suggest the
      possible explanation about the effect of urea on NOX activity at the molecular
      level. Both, X-ray structure and molecular dynamics (MD) simulations, show open
      conformation of the active site represented by approximately 0.9 nm distance
      between the indole ring of Trp47 and the isoalloxazine ring of FMN412. In this
      conformation, the substrate molecule can bind in the active site without sterical
      restraints. MD simulations also indicate more stable conformation of the active
      site called "closed" conformation. In this conformation, Trp47 and the
      isoalloxazine ring of FMN412 are so close to each other (approximately 0.5 nm)
      that the substrate molecule is unable to bind between them without perturbing
      this conformation. The open/close transition of the active site between Trp47 and
      the flavin ring is accompanied by release of the "tightly" bound water molecule
      from the active site--cofactor assisted gating mechanism. The presence of urea in
      aqueous solutions of NOX prohibits closing of the active site and even unlocks
      the closed active site because of the concomitant binding of a urea molecule in
      the active site cavity. The binding of urea in the active site is stabilized by
      formation of one/two persistent hydrogen bonds involving the carbonyl group of
      the urea molecule. Our report represents the first MD study of an enzyme from the
      novel flavoprotein family of nitroreductases and flavin reductases. The common
      occurrence of aromatic residues covering the active sites in homologous enzymes
      suggests the possibility of a general gating mechanism and the importance of
      local dynamics within this flavoprotein family.

PMID- 16642503
TI  - Sensorineural deafness, hydrocephalus and structural brain abnormalities in two
      sisters: the Chudley-McCullough syndrome.
AB  - We describe an Italian family in which two sisters have macrocephaly due to
      hydrocephalus, and sensorineural hearing loss in addition to other brain
      abnormalities demonstrated by Magnetic resonance imaging (MRI). The girls, born
      to healthy non-consanguineous parents, have borderline psychomotor development
      delay (probably due to hearing defect) and minor dysmorphisms. The clinical
      picture fits the Chudley-McCullough syndrome, an autosomal recessive condition,
      to date described in only five families. Our data, in particular the
      neuroradiological findings, include all brain anomalies variably reported in
      previous works (hydrocephalus, corpus callosum partial agenesis, interhemispheric
      cyst, cerebral and cerebellar cortex dysplasia), thus illustrating the full
      phenotype of the syndrome.

PMID- 16642504
TI  - Response to the Alvarez Nava and Puerta "Y-chromosome microdeletions in
      45,X/46,XY patients".

PMID- 16642505
TI  - Desbuquois syndrome in three sisters with significantly different lengths of
      survival.

PMID- 16642506
TI  - A compound heterozygote harboring novel and recurrent DTDST mutations with
      intermediate phenotype between atelosteogenesis type II and diastrophic
      dysplasia.
AB  - Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate transporter
      required for the synthesis of sulfated proteoglycans in the cartilage. Over 30
      mutations have been described in the DTDST gene, which result in a continuous
      clinical spectrum of recessively inherited chondrodysplasias, including, in order
      of increasing severity, a recessive form of multiple epiphyseal dysplasia (rMED),
      diastrophic dysplasia (DTD), atelosteogenesis type II (AO-II) and achondrogenesis
      1B (ACG-1B). Correlation between disease severity and residual sulfate transport
      activity has been reported. Here we report a patient with DTDST mutations, whose
      manifestations fell in a range between AO-II and DTD. The patient was a compound
      heterozygote for the recurrent c.835C>T (p.R279W) and novel c.1987G>A (p.G663R)
      mutations. Immunocytochemical analysis in HEK293 cells showed that the p.G663R
      mutation was localized within the cytoplasm, and not to the cell membrane,
      suggesting p.G663R is a loss-of-function mutation. Our case supports the
      previously described correlation between the severity of the phenotype and the
      putative level of residual transport function.

PMID- 16642507
TI  - Schizophrenia in an adult with 6p25 deletion syndrome.
AB  - Chromosomal deletions at 6p25-p24 are rare findings in patients with
      developmental delay. There is limited information about the adult phenotype. We
      present a 36-year-old patient with schizophrenia, mild mental retardation,
      progressive hearing deficits, and characteristic facial features. Ocular
      (Axenfeld-Rieger anomaly) abnormalities were diagnosed in infancy; vision,
      however, has remained unimpaired. There were no other major congenital anomalies.
      Brain imaging showed only minor changes. There was no family history of
      intellectual deficits or psychosis. Karyotyping revealed a 6p25 deletion, and
      detailed fluorescence in situ hybridization (FISH) analyses using 23 probes
      confirmed a 6.7 Mb 6p25-pter deletion. The breakpoint is near a possible 6p25-p24
      locus for schizophrenia. Psychotic illness may be part of the neurodevelopmental
      abnormalities and long-term outcome of patients with 6p terminal deletions. Other
      similarly affected patients likely remain to be diagnosed in adult populations of
      schizophrenia and/or mental retardation.

PMID- 16642508
TI  - The neonatal phenotype of Prader-Willi syndrome.

PMID- 16642509
TI  - Chilean primary health workers' knowledge about folic acid supplementation for
      the prevention of neural tube defects.

PMID- 16642510
TI  - Keutel syndrome with overlapping features of cutis laxa: a new variant.

PMID- 16642511
TI  - Impaired proliferation and migration in human Miller-Dieker neural precursors.
AB  - OBJECTIVE: Miller-Dieker syndrome (MDS) is a malformation of cortical development
      that results in lissencephaly (meaning smooth brain). This disorder is caused by
      heterozygous deletions on chromosome 17p13.3, including the lissencephaly 1
      (LIS1) gene. Various mouse models have been used as an experimental paradigm in
      understanding human lissencephaly, but clear limitations exist in these studies,
      particularly because mice are naturally lissencephalic. Thus, the objective of
      this article was to establish human neural precursor cell lines from postmortem
      MDS tissue and to characterize the pathological cellular processes that
      contribute to the human lissencephalic phenotype. METHODS: Human neural
      precursors were isolated and expanded from the frontal cortices of a 33-week
      postmortem fetus with MDS and an age-matched control subject. Relative rates of
      proliferation and cell death were assessed in vitro, whereas the migration of
      precursors was examined after transplantation in vivo. RESULTS: Precursors showed
      haploinsufficiency of the LIS1 gene and a reduction in LIS1 protein. Precursors
      could also differentiate into both neurons and glia. MDS precursors demonstrated
      impairments in neuronal migration, diminished rates of cell proliferation, and
      increased cell death. INTERPRETATION: These results suggest that, in addition to
      migration, disruption in cell proliferation could play a more important role in
      the development of lissencephaly than previously suspected.

PMID- 16642512
TI  - Natural products research: renaissance with strengthened integration of biology
      and chemistry.

PMID- 16642513
TI  - To boldly pass the metal-metal quadruple bond.

PMID- 16642514
TI  - Proteolytic actuation of nanoparticle self-assembly.

PMID- 16642516
TI  - Shape control of semiconductor and metal oxide nanocrystals through nonhydrolytic
      colloidal routes.
AB  - Inorganic nanocrystals with tailored geometries exhibit unique shape-dependent
      phenomena and subsequent utilization of them as building blocks for the
      fabrication of nanodevices is of significant interest. Herein, we review the
      recent developments in the shape control of colloidal nanocrystals with a focus
      on the scientifically and technologically important semiconductor and metal oxide
      nanocrystals obtained by nonhydrolytic synthetic methods. Many structurally
      unprecedented motifs have been discovered including polyhedrons, rods and wires,
      plates and prisms, and other advanced shapes such as branched rods, stars,
      inorganic dendrites, and dumbbells. The currently proposed shape-guiding
      mechanisms are presented and the important pioneering studies on the assembly of
      shape-controlled nanocrystals into ordered superlattices and the fabrication of
      prototype advanced nanodevices are discussed.

PMID- 16642517
TI  - Expression of Alternaria solani PKSF generates a set of complex reduced-type
      polyketides with different carbon-lengths and cyclization.

PMID- 16642518
TI  - Modulation of infectivity in phage display as a tool to determine the substrate
      specificity of proteases.
AB  - Proteases play an important role in human and animal diseases. Rapid
      determination of substrate specificity is possible through the use of substrate
      phage display; however, current methods possess several drawbacks. They require
      phage-immobilization and cannot be used for infectivity-destroying or affinity
      tag-destroying proteases; this can make entire libraries useless. To overcome
      these limitations, here we introduce infectivity-modulated phage display (IMOP).
      IMOP uses a protease-resistant and infectivity-reducing tag fused to substrate
      displaying polyvalent phages, and the specific cleavage of the substrate
      increases the infectivity of the phages by releasing the infectivity-reducing
      tag. The resulting phages were first tested with the infectivity-destroying
      detergent protease subtilisin; this resulted in a highly specific substrate at a
      200-fold enrichment. In a second example, the protease ompT was used and led to
      an enrichment of the known double-arginine motif. The IMOP system thus
      substantially improves and simplifies previous systems.

PMID- 16642520
TI  - Heteropolynuclear palladium complexes with pyrazolate and its 3-tert-butyl
      derivatives: the effect of heterometal ions on the rate of isomerization.
AB  - The heteropolynuclear complexes [Pd(2)M'(2)(mu-pz)(6)] (M'=Ag (1), Au (2);
      pzH=pyrazole), HT-[Pd(2)M'(2)(mu-3-tBupz)(6)] (M'=Ag (3 a), Au (4 a); 3-tBupzH=3
      tert-butylpyrazole), and HH-[Pd(2)Au(2)(mu-3-tBupz)(6)] (4 b) have been prepared
      and some of them were structurally characterized. When 3-tert-butylpyrazolate was
      employed as a bridging ligand, two linkage isomers (head-to-tail (HT) and head-to
      head (HH)) arise from the difference in orientation of the substituent groups on
      the pyrazolate bridges between the two Pd atoms. (1)H NMR spectroscopy has been
      used to identify and to follow the reversible stereochemical rearrangement of the
      HH isomer of [Pd(2)Ag(2)(mu-3-tBupz)(6)] (3 b) to form the HT isomer 3 a in
      CDCl(3) and the HT isomer of [Pd(2)Au(2)(mu-3-tBupz)(6)] (4 a) to form the HH
      isomer 4 b in C(6)D(6). Kinetic studies of the reaction have established the rate
      law to be -d(HH)/dt=d(HT)/dt=k(2)[HH]-k(1)[HT] for 3 b and 
      d(HT)/dt=d(HH)/dt=k(1)[HT]-k(2)[HH] for 4 a, where k(1) and k(2) denote the rate
      of isomerization from the HT to the HH isomer and that from the HH to the HT
      isomer, respectively. For typical runs at 50 degrees C in C(6)D(6), k(1)=13.8x10(
      5) s(-1), k(2)=18.6x10(-5) s(-1), and K(eq)=k(2)/k(1)=1.24 for 3 b, and
      k(1)=1.26x10(-5) s(-1), k(2)=3.52x10(-5) s(-1), and K(eq)=k(1)/k(2)=0.36 for 4 a.
      Temperature-dependent rate measurements reveal DeltaH(not equal) and DeltaS(not
      equal) to be 100(1) kJ mol(-1) and 0(3) J mol(-1) K(-1) for 3 b and 112(5) kJ
      mol(-1) and 20(17) J mol(-1) K(-1) for 4 a, respectively. The rate of
      isomerization is essentially unaffected by the concentration of the complex or by
      the presence of neutral bridging ligands. These data and observations imply that
      the isomerization involves an intramolecular exchange process.

PMID- 16642519
TI  - Hydrogen-isotope scrambling on doped sodium alanate.

PMID- 16642521
TI  - trans-cis Photoisomerization of the styrylpyridine Ligand in [Re(CO)3(2,2'
      bipyridine)(t-4-styrylpyridine)]+: role of the metal-to-ligand charge-transfer
      excited states.
AB  - The trans-cis isomerization of the styrylpyridine carbon-carbon double bond
      induced by visible light irradiation in fac-[Re(CO)(3)(bpy)(stpy)](+) (bpy = 2,2'
      bipyridine; stpy = t-4-styrylpyridine) has been investigated by means of quantum
      chemical methods. The structures of the various cis and trans conformers of
      [Re(CO)(3)(bpy)(stpy)](+) have been optimized at the density functional theory
      (DFT) level. Three rotational conformers for the most stable trans isomer lie
      within 2.3 kJ mol(-1) each other. The energy difference between the cis and trans
      isomers is 27.0 kJ mol(-1). The electronic spectroscopy of the most stable
      conformers has been investigated by time-dependent DFT (TD-DFT) and complete
      active space self-consistent field/CAS second order perturbation theory
      (CASSCF/CASPT2) calculations. The lowest absorption bands are dominated by metal
      to-ligand charge-transfer (MLCT, d(Re)-->pi*(bpy)) transitions calculated at
      about 25,000 cm(-1) and by a strong intraligand (1)IL (pi(stpy)-->pi*(stpy))
      transition in the near UV region. On the basis of CASSCF potential energy curves
      (PECs) calculated as a function of the torsion angle of the C=C bond of the
      styrylpyridine ligand, it is shown that the role of the low-lying MLCT states is
      important in the photoisomerization mechanism. In contrast to the free organic
      ligand, in which the singlet mechanism is operational via the (1)IL (S(1)) and
      electronic ground (S(0)) states, coordination to the rhenium steers the
      isomerization to the triplet PEC corresponding to the (3)IL state. From the
      (3)IL(t) (t = trans) the system evolves to the perpendicular intermediate
      (3)IL(p) (p = perpendicular) following a 90 degrees rotation around the
      styrylpyridine C=C bond. The metal center acts as a photosensitizer because of
      the presence of photoactive MLCT states under visible irradiation. The position
      of the crossing between the (3)IL and electronic ground state PEC determines the
      quantum yield of the isomerization process.

PMID- 16642522
TI  - Ruthenium complexes of thiocinnamaldehydes: synthesis, structure, and [4+2]
      cycloaddition reactions.
AB  - Ruthenium hydrogensulfido complexes [CpRu(P-P)(SH)] ((P-P)=Ph(2)PCH(2)PPh(2)
      (dppm), Ph(2)PC(2)H(4)PPh(2) (dppe)) were obtained from the corresponding chloro
      complexes by Cl/SH exchange. Condensation with a range of cinnamaldehydes gave
      thiocinnamaldehyde complexes [CpRu(P-P)(S=CH-CR(2)=CHR(1))]PF(6) (R(1)=C(6)H(4)X,
      R(2)=H, Me, X=H, OMe, NMe(2), Cl, NO(2)) as highly-colored crystalline compounds.
      The thiocinnamaldehyde complexes undergo [4+2]-cycloaddition reactions with vinyl
      ethers CH(2)=CHOR(3) (R(3)=Et, Bu) and styrenes H(2)C=CHC(6)H(4)Y (Y=H, Me, OMe,
      Cl, Br, NO(2)) to give complexes of 2,4,5-trisubstituted 3,4-dihydro-2H
      thiopyrans as mixtures of two diastereoisomers. The rate of addition of para
      substituted styrenes H(2)C=CHC(6)H(4)Y to [CpRu(dppm)(S=CH-CH=CHPh)]PF(6)
      increases in the series Y=NO(2), Br, Cl, H, Me, OMe, indicating that the
      cycloaddition is dominated by the HOMO(dienophile)-LUMO(diene) interaction. The
      strained dienophiles norbornadiene and norbornene also add, giving ruthenium
      complexes of 3-thia-tricyclo[6.2.1.0(2,7)]undeca-4,9-dienes and 3-thia
      tricyclo[6.2.1.0(2,7)]undec-4-enes, respectively. Addition reactions with
      acrolein, methacrolein, methyl vinyl ketone, acrylic ester, or ethyl propiolate
      finally yielded ruthenium complexes of 3,4-disubstituted 3,4-dihydro-2H
      thiopyrans and 4H-thiopyrans, respectively.

PMID- 16642523
TI  - High-spin- and low-spin-state structures of [Fe(chloroethyltetrazole)6](ClO4)2
      from synchrotron powder diffraction data.
AB  - The spin-crossover complex [Fe(teec)(6)](ClO(4))(2) (teec = chloroethyltetrazole)
      exhibits a 50 % incomplete spin crossover in the temperature range 300-30 K. Time
      resolved synchrotron powder diffraction experiments have been carried out to
      elucidate its structural behavior. We report crystal structure models of this
      material at 300 K (high spin) and 90 K (low spin), as solved from synchrotron
      powder diffraction data by using Genetic Algorithm and Parallel Tempering
      techniques and refined with Rietveld refinement. During short synchrotron powder
      diffraction experiments (five minutes duration) two distinguishable lattices were
      observed the quantities of which vary with temperature. The implication of this
      phenomenon, that is interpreted as a structural phase transition associated with
      the high-to-low spin crossover, and the structural characteristics of the high
      spin and low-spin models are discussed in relation to other compounds showing a
      similar type of spin-crossover behavior.

PMID- 16642524
TI  - Exploring the hydration of Pb2+: ab initio studies and first-principles molecular
      dynamics.
AB  - Even though lead is a well-known toxicant widely scattered throughout the world
      since antiquity, its chemistry is poorly documented at the molecular level. Here
      we investigate the hydration of the Pb(2+) ion by means of first-principles
      molecular dynamics (Car-Parrinello molecular dynamics, CPMD). We found that the
      hydrated cation is heptacoordinated in a dynamically holodirected arrangement
      roughly corresponding to a fluxional distorted pentagonal bipyramid. The time
      averaged Pb-O bond length is especially large and amounts to 2.70 A with an
      associated root-mean-square deviation of 0.26 A. This results from a dynamic
      exchange between short (<2.6 A), intermediate (2.6-3.0 A) and long (>3.0 A) Pb-O
      bonds. The latter very long Pb-O distance implies that the determination of the
      coordination number n(c) from experimental work may not necessarily yield values
      directly comparable to the theoretical value of n(c)=7, since not all
      experimental techniques would recognize such a long distance as a bond to the
      metal cation. Pronounced disorders are evidenced in the second shell,
      characteristic of a chaotropic cation, and exchanges between the first and second
      shells cannot be excluded on a timescale of a few tens of picoseconds.

PMID- 16642525
TI  - FTIR studies of iron-carbonyl intermediates in allylic alcohol
      photoisomerization.
AB  - The 532 or 355 nm laser-induced photoisomerization of allylic alcohols to
      aldehydes catalyzed by [Fe(3)(CO)(12)] or [Fe(CO)(4)PPh(3)] in hexane was
      investigated. The Fourier transform infrared (FTIR) absorption spectra of iron
      carbonyl intermediate species such as [Fe(CO)(5)], [Fe(CO)(4)(R-C(3)H(4)OH)], and
      more importantly the pi-allyl iron-carbonyl hydride species [FeH(CO)(3)(R
      C(3)H(3)OH)] (R=H, Me, Ph) were recorded during the catalytic process using
      [Fe(3)(CO)(12)] as the catalytic precursor. When [Fe(CO)(4)PPh(3)] was photolyzed
      with 355 nm, [FeH(CO)(3)(R-C(3)H(3)OH)] was also generated indicating the common
      occurrence of the species in these two systems. The pi-allyl hydride species is
      long believed to be a key intermediates and its detection here lends support to
      the pi-allyl mechanism of the photoisomerization of allyl alcohols.

PMID- 16642526
TI  - Azobenzene as conformational switch in model peptides.
AB  - The photoinduced isomerization of azobenzene between the extended (trans) and
      compact (cis) conformations is reversibly triggered by light of two differing
      wavelengths. The resulting changes in molecular geometry have been extensively
      utilized to photoswitch transformations in chemical species reversibly for
      applications in optoelectronic devises as well as to photocontrol conformational
      states in (bio)polymers. The high isomerization yield, remarkable photostability
      and ultrafast kinetics (few ps) of azobenzene are well suited for the design of
      small, defined model systems that allow detailed folding studies to be carried
      out both experimentally and theoretically on the same molecules. In our and other
      laboratories such systems were recently obtained with cyclic peptides of defined
      conformational preferences as well as with alpha-helical and beta-hairpin
      peptides. These should, by comparison of simulation and experiment, permit an
      assessment and improvement of the theoretical description on the one hand and a
      detailed interpretation of the ultrafast conformational dynamics on the other.
      The phototriggered changes in conformational states lead to concurrent changes in
      biophysical properties that can be exploited in the photocontrol of biochemical
      and biological events, as exemplarily discussed with redox-active cyclic bis
      cysteinyl peptides and receptor ligands.

PMID- 16642527
TI  - Reaction of cytidine nucleotides with cyanoacetylene: support for the
      intermediacy of nucleoside-2',3'-cyclic phosphates in the prebiotic synthesis of
      RNA.
AB  - A robust and prebiotically plausible synthesis of RNA is a key requirement of the
      "RNA World" hypothesis, but, to date, no such synthesis has been demonstrated.
      Monomer synthesis strategies involving attachment of preformed nucleobases to
      sugars have failed, and, even if activated 5'-nucleotides could be made, the
      hydrolysis of these intermediates in water makes their efficient oligomerisation
      appear unlikely. We recently reported a synthesis of cytidine-2',3'-cyclic
      phosphate 1 (C>p) in which the nucleobase was assembled in stages on a sugar
      phosphate template. However, 2',3'-cyclic nucleotides (N>p's) also undergo
      hydrolysis, in this case giving a mixture of the 2'- and 3'-monophosphates. This
      hydrolysis has previously been seen as making the, otherwise promising,
      oligomerisation of N>p's seem as unlikely as that of the 5'-activated
      nucleotides. We now find that cyanoacetylene, the reagent used for the second
      stage of nucleobase assembly in the synthesis of C>p, also reverses the effect of
      the hydrolysis by driving efficient cyclisation of C2'p and C3'p back to C>p.
      Excess cyanoacetylene also derivatises the nucleobase, but this modification is
      reversible at neutral pH. These findings significantly strengthen the case for
      N>p's in a prebiotic synthesis of RNA.

PMID- 16642528
TI  - Characterization of BlsM, a nucleotide hydrolase involved in cytosine production
      for the biosynthesis of blasticidin S.
AB  - Biosynthesis of the antifungal agent blasticidin S in Streptomyces
      griseochromogenes requires the formation of free cytosine. The blsM gene in the
      blasticidin S gene cluster is predicted to encode a protein that has sequence
      homology with several nucleoside transferases. In vitro analysis of recombinant
      BlsM revealed that the enzyme functions as a nucleotide hydrolase and catalyzes
      the formation of free cytosine by using cytidine 5'-monophosphate (CMP) as the
      preferred substrate. Cytosine production was significantly lower with CDP, CTP,
      and dCMP as alternate substrates. BlsM was also observed to have low-level
      cytidine deaminase activity, converting cytidine and deoxycytidine to uridine and
      deoxyuridine, respectively. Point mutations were introduced in blsM at putative
      catalytic residues to generate three mutant enzymes, BlsM Ser98Asp, Glu104Ala,
      and Glu104Asp. All three mutants lost CMP hydrolysis activity, but the Ser98Asp
      mutant showed a modest increase in cytidine deaminase activity.

PMID- 16642529
TI  - Macropodumines A-C: novel pentacyclic alkaloids with an unusual skeleton or
      zwitterion moiety from Daphniphyllum macropodum Miq.
AB  - Three novel alkaloids, macropodumines A-C (1-3), were isolated from the stem of
      Daphniphyllum macropodum Miq. Interestingly, the structure of macropodumine A (1)
      was characterized as having a fused pentacyclic system including an unusual
      eleven-membered macrolactone ring, whereas macropodumine B (2) contains a rare
      cyclopentadienyl carbanion, which is stabilized as a zwitterion by an internal
      iminium cation. The structures of these new metabolites were established on the
      basis of their detailed spectroscopic analysis. In particular, the unique
      structure of zwitterion 2 was further confirmed by using single-crystal X-ray
      diffraction analysis.

PMID- 16642530
TI  - A DNA-binding copper(I) metallosupramolecular cylinder that acts as an artificial
      nuclease.
AB  - The DNA binding of a dicationic pyridylimine-based dicopper(I)
      metallosupramolecular cylinder is reported together with its ability to act as an
      artificial nuclease. The cylinder binds strongly to DNA; more strongly than the
      spherical dication [Ru(phen)(3)](2+) (phen=1,10-phenanthroline), but more weakly
      than the corresponding tetracationic cylinders. DNA coiling effects are not
      observed with this dication, in contrast to the situation with the previously
      reported tetracationic cylinder involving a similar ligand. Linear dichroism (LD)
      data suggests that the dicopper cylinder binds in a different orientation from
      that of the tetracationic iron cylinder. Furthermore, the dicopper cylinder shows
      DNA-cleavage activity in the presence of peroxide. Of particular note is that the
      cylinder displays a marked and unusual ability to cleave both DNA strands at the
      same site, probably reflecting its dinuclear nature and possibly its mode of
      binding to the DNA.

PMID- 16642531
TI  - Pyrimidinyl nitronyl nitroxides.
AB  - The chemistry of 2,2,4,4-substituted pentane derivatives has been investigated
      with the aim of providing a flexible and versatile synthetic route to pyrimidinyl
      nitronyl nitroxides, in which the bis-N-oxy fragment is incorporated in a six
      membered ring. The synthesis of 2,4-diamino-2,4-dimethylpentane and 2,4
      bis(hydroxylamino)-2,4-dimethylpentane, convenient precursors of these
      nitroxides, is described and full characterization of a series of pyrimidinyl
      nitronyl nitroxides is reported, along with a preliminary study of their
      coordination properties.

PMID- 16642532
TI  - Anticancer cyclometalated [Au(III)m(C(wedge)N(wedge)C)mL]n+ compounds: Synthesis
      and cytotoxic properties.
AB  - A series of cyclometalated gold(III) compounds [Au(m)(C(wedge)N(wedge)C)mL]n+ (m
      = 1-3; n = 0-3; HC(wedge)N(wedge)CH = 2,6-diphenylpyridine) was prepared by
      ligand substitution reaction of L with N-donor or phosphine ligands. The
      [Au(m)(C(wedge)N(wedge)C)mL]n+ compounds are stable in solution in the presence
      of glutathione. Crystal structures of the gold(III) compounds containing bridging
      bi- and tridentate phosphino ligands reveal the presence of weak intramolecular
      pi pi stacking between the [Au(C(wedge)N(wedge)C)]+ units. Results of MTT assays
      demonstrated that the [Au(m)(C(wedge)N(wedge)C)mL]n+ compounds containing
      nontoxic N-donor auxiliary ligands (2) exert anticancer potency comparable to
      that of cisplatin, with IC50 values ranging from 1.5 to 84 microM. The use of
      [Au(C(wedge)N(wedge)C)(1-methylimidazole)]+ (2 a) as a model compound revealed
      that the gold(III)-induced cytotoxicity occurs through an apoptotic cell-death
      pathway. The cell-free interaction of 2 a with double-stranded DNA was also
      examined. Absorption titration showed that 2 a binds to calf-thymus DNA (ctDNA)
      with a binding constant of 4.5 x 10(5) dm3 mol(-1) at 298 K. Evidence from gel
      mobility-shift assays and viscosity measurements supports an intercalating
      binding mode for the 2 a-DNA interaction. Cell-cycle analysis revealed that 2 a
      causes S-phase cell arrest after incubation for 24 and 48 hours. The cytotoxicity
      of 3 b-g toward cancer cells (IC50 = 0.04-4.3 microM) correlates to that of the
      metal-free phosphine ligands (IC50 = 0.1-38.0 microM), with
      [Au2(C(wedge)N(wedge)C)2(mu-dppp)]2+ (3 d) and dppp (dppp = 1,2
      bis(diphenylphosphino)propane) being the most cytotoxic gold(III) and metal-free
      compounds, respectively. Compound 3 d shows a cytotoxicity at least ten-fold
      higher than the other gold(III) analogues; in vitro cellular-uptake experiments
      reveal similar absorptions for all the gold(III) compounds into nasopharyngeal
      carcinoma cells (SUNE1) (1.18-3.81 ng/cell; c.f., 3 d = 2.04 ng/cell), suggesting
      the presence of non-gold-mediated cytotoxicity. Unlike 2 a, both gold(III)
      compounds [Au(C(wedge)N(wedge)C)(PPh3)]+ (3 a) (PPh3 = triphenylphosphine) and
      [Au2(C(wedge)N(wedge)C)2(mu-dppp)]2+ (3 d) interact only weakly with ctDNA and do
      not arrest the cell cycle.

PMID- 16642533
TI  - Synthesis and structural model of an alpha(2,6)-sialyl-t glycosylated MUC1
      eicosapeptide under physiological conditions.
AB  - To study the effect of O-glycosylation on the conformational propensities of a
      peptide backbone, a 20-residue peptide (GSTAPPAHGVTSAPDTRPAP) representing the
      full length tandem repeat sequence of the human mucin MUC1 and its analogue
      glycosylated with the (2,6)-sialyl-T antigen on Thr11, were prepared and
      investigated by NMR and molecular modeling. The peptides contain both the GVTSAP
      sequence, which is an effective substrate for GalNAc transferases, and the PDTRP
      fragment, a known epitope recognized by several anti-MUC1 monoclonal antibodies.
      It has been shown that glycosylation of threonine in the GVTSAP sequence is a
      prerequisite for subsequent glycosylation of the serine at GVTSAP. Furthermore,
      carbohydrates serve as additional epitopes for MUC1 antibodies. Investigation of
      the solution structure of the sialyl-T glycoeicosapeptide in a H(2)O/D(2)O
      mixture (9:1) under physiological conditions (25 degrees C and pH 6.5) revealed
      that the attachment of the saccharide side-chain affects the conformational
      equilibrium of the peptide backbone near the glycosylated Thr11 residue. For the
      GVTSA region, an extended, rod-like secondary structure was found by restrained
      molecular dynamics simulation. The APDTR region formed a turn structure which is
      more flexibly organized. Taken together, the joined sequence GVTSAPDTR represents
      the largest structural model of MUC1 derived glycopeptides analyzed so far.

PMID- 16642534
TI  - Lewis base stabilized phosphanylborane.
AB  - The abstraction of the Lewis acid from [W(CO)(5)(PH(2)BH(2)NMe(3))] (1) by an
      excess of P(OMe(3))(3) leads to the quantitative formation of the first Lewis
      base stabilized monomeric parent compound of phosphanylborane [H(2)PBH(2)NMe(3)]
      2. Density functional theory (DFT) calculations have shown a low energetic
      difference between the crystallographically determined antiperiplanar arrangement
      of the lone pair and the trimethylamine group relative to the P-B core and the
      synperiplanar conformation. Subsequent reactions with the main-group Lewis acid
      BH(3) as well as with an [Fe(CO)(4)] unit as a transition-metal Lewis acid led to
      the formation of [(BH(3))PH(2)BH(2)NMe(3)] (3), containing a central H(3)B-PH(2)
      BH(2) unit, and [Fe(CO)(4)(PH(2)BH(2)NMe(3))] (4), respectively. In oxidation
      processes with O(2), Me(3)NO, elemental sulfur, and selenium, the
      boranylphosphine chalcogenides [H(2)P(Q)BH(2)NMe(3)] (Q = S 5 b; Se 5 c) as well
      as the novel boranyl phosphonic acid [(HO)(2)P(O)BH(2)NMe(3)] (6 a) are formed.
      All products have been characterized by spectroscopic as well as by single
      crystal X-ray structure analysis.

PMID- 16642535
TI  - Electron transfer in nonpolar solvents in fullerodendrimers with peripheral
      ferrocene units.
AB  - Two new fullerodendrimers, with two and four ferrocene units on their periphery,
      have been synthesized by 1,3-dipolar cycloaddition reactions between the
      corresponding azomethine ylides and C(60). These new compounds have been studied
      by using cyclic voltammetry and UV/Vis spectroscopy. Weak intramolecular
      interactions between the fullerene cage and the ferrocene groups have been found.
      The photochemical events of both fullerene-ferrocene dendrimers have been probed
      by means of steady-state and time-resolved techniques. The steady-state emission
      intensities of the fulleropyrrolidine-ferrocene dendrimers 1 and 2 were found to
      be quenched relative to the N-methylfulleropyrrolidine without substituents that
      was used as a model. The nanosecond transient absorption spectral studies
      revealed efficient charge separation in both systems, even in toluene. The
      lifetimes of the (C(60))(*-)-(dendron)(*+) are higher for the second-generation
      fullerodendrimer (with four ferrocene units) and they are of the order of tens of
      nanoseconds in toluene and hundreds of nanoseconds in polar solvents.

PMID- 16642536
TI  - Neutral helium compounds: theoretical evidence for a large class of polynuclear
      complexes.
AB  - Ab initio calculations at the MP2 and CCSD(T) levels of theory disclose the
      conceivable existence of neutral complexes containing up to four helium atoms.
      These species are formally obtained by replacing the hydrogen atoms of parent
      molecules such as CH(4), SiH(4), NH(3), PH(3), H(2)O, H(2)S, C(2)H(2), C(2)H(4),
      and C(6)H(6) with -NBeHe moieties, which behave as monovalent functional groups
      containing helium. The geometries and vibrational frequencies of these
      M(NBeHe)(n) (n>1; M=central moiety) polyhelium complexes have been investigated
      at the MP2(full)/6-31G(d) level of theory, and their stability with respect to
      the loss of helium atom(s) has been evaluated by means of single-point
      calculations at the CCSD(T)/6-311G(d,p) level of theory. Molecules such as
      H(n)C(NBeHe)(4-n) and H(n)Si(NBeHe)(4-n) (n=0-3), C(2)(NBeHe)(2), and ortho-,
      meta-, and para-C(6)H(4)(NBeHe)(2) were invariably characterized as energy
      minima, and were found to be stable with respect to the loss of helium atom(s) by
      approximately 4-5 kcal mol(-1). On the other hand, species such as C(2)(NBeHe)(4)
      and C(6)(NBeHe)(6) were characterized as high-order saddle points on the
      potential-energy surface, and were unstable with respect to helium atom(s) loss
      owing to the bending motion of the -NBeHe groups. The molecules containing N, P,
      O, or S as the central atom also showed a variable topology and include second
      order saddle points such as S(NBeHe)(2), third-order saddle points such as
      HN(NBeHe)(2), but also minimum-energy structures such as O(NBeHe)(2) and
      HP(NBeHe)(2), which are also stable by approximately 5 kcal mol(-1) with respect
      to the helium atom(s) loss. These results suggest the conceivable existence of
      an, in principle, very large class of M(NBeHe)(n) (n>1) polyhelium complexes,
      whose stability may be substantially affected by the nature and the size of the
      central moiety M. Atoms-in-Molecules (AIM) calculations on selected species
      invariably suggest that, in our investigated M(NBeHe)(n) (n>1) compounds, the
      beryllium-helium interaction is essentially electrostatic.

PMID- 16642537
TI  - Investigating nonribosomal peptide and polyketide biosynthesis by direct
      detection of intermediates on >70 kDa polypeptides by using Fourier-transform
      mass spectrometry.

PMID- 16642538
TI  - Firefly luciferase produces hydrogen peroxide as a coproduct in dehydroluciferyl
      adenylate formation.
AB  - Firefly luciferase catalyzes the synthesis of H2O2 from the same substrates as
      the bioluminescence reaction: ATP and luciferin (D-LH2). About 80% of the enzyme
      bound intermediate D-luciferyl adenylate (D-LH2-AMP) is oxidized into
      oxyluciferin, and a photon is emitted during this reaction. The enzyme pathway
      responsible for the generation of H2O2 is a side reaction in which D-LH2-AMP is
      oxidized into dehydroluciferyl adenylate (L-AMP). Like the bioluminescence
      reaction, the luciferase-catalyzed synthesis of H2O2 and L-AMP is a
      stereospecific process, involving only the natural D enantiomer. However, the
      intramolecular electron transfer postulated as essential to the light emission
      process is not involved in this side reaction.

PMID- 16642539
TI  - Protected 32P-labels in deoxyribonucleotides: investigation of sequence
      selectivity of DNA photocleavage by enediyne-, fulvene-, and acetylene-lysine
      conjugates.

PMID- 16642540
TI  - Controlled self-assembly behavior of an amphiphilic bisporphyrin-bipyridinium
      palladium complex: from multibilayer vesicles to hollow capsules.

PMID- 16642541
TI  - CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly.
AB  - INTRODUCTION: The elderly are at increased risk for medication-related adverse
      events. Recent reports indicate that venlafaxine may put the elderly at increased
      risk of cardio- and cerebrovascular adverse events. We investigated the
      relationship between the CYP2D6 polymorphism and steady-state plasma
      concentration of venlafaxine (VEN) and its primary metabolite o
      desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for
      major depression in order to explore the contribution of pharmacogenetics to
      medication tolerability. METHODS: Forty-six elderly participants received
      venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady
      state plasma levels of VEN and ODV were determined. RESULTS: Sixty-five percent
      of participants were homozygous of the wild type (WT) allele, whereas 35% carried
      one or more variant alleles associated with intermediate and poor 2D6 metabolizer
      status. VEN concentration per unit dose was significantly higher and ODV
      concentration per unit dose was significantly lower in participants who carried
      one or more variant alleles compared to participants who were homozygous for the
      WT allele. The VEN and ODV concentrations per unit dose were also correlated with
      creatinine clearance. CYP2D6 genotype was not associated with medication
      associated side-effects. CONCLUSIONS: Plasma dose-corrected concentrations of VEN
      and ODV correlated with genetically determined CYP2D6 enzymatic activity in
      depressed elders treated with venlafaxine-XR. This relationship was not masked by
      the effects of age-related illness or polypharmacy. Future clinical application
      of pharmacogenetics to examine 2D6-dependent medications may help reduce the
      incidence of medication adverse events particularly in those elders at higher
      risk for medication adverse events due to impaired renal or cardiac function.

PMID- 16642542
TI  - Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression
      of amnestic mild cognitive impairment.
AB  - BACKGROUND: Predictors of progression to dementia in individuals with mild
      cognitive impairment (MCI) define different groups with higher risks of
      progression. To date, efforts to differentiate those who will progress to
      dementia from those who will not have proved inconclusive, and while grades of
      risk have been identified, their generalizability is not clear. AIM: To examine
      the clinical and socio-demographical risk factors for progression of memory
      decline in a sample of subjects with referred memory complaints who met criteria
      for amnestic MCI. METHODS AND MATERIALS: Seventy-four subjects consecutively
      recruited who met the operational criteria for amnestic MCI. They underwent
      multidimensional assessment and a neuropsychological battery at baseline and at
      follow-up, after one year. Memory decline was defined using the short story mean
      score change (at follow-up and at baseline). Subjects showing memory decline,
      with or without conversion to AD over time, were classified as having progressive
      MCI; subjects that remained unchanged or improved during follow-up were
      considered as having stable MCI. RESULTS: Subjects with progressive MCI (n = 39,
      53%) were older (p = <0.001) and more educated (p = 0.01) compared to stable MCI
      (n = 35, 47%) and their global cognitive performances, at baseline, were more
      compromised when assessed by ADAS-Cog (p = 0.05). Antihypertensive drug
      prescription was greater in the stable MCI compared to progressive MCI (p = 0.01)
      and significant higher levels of plasma total homocysteine were observed in
      progressive MCI (p = 0.03). When analyzed in a logistic regression model, the
      prescription of Angiotensin Converting Enzyme Inhibitors (ACE) was found to be
      independently associated to the stability of cognitive function, whereas older
      age, higher education, higher levels of plasma total homocysteine and total ADAS
      Cog basal score were independently associated with the progression of cognitive
      decline. CONCLUSIONS: Older age, higher education, poor global cognitive
      performance, higher levels of plasma total homocysteine are independently
      associated with the progression of memory decline while the prescription of ACE
      Inhibitors is a protective factor for cognitive deterioration.

PMID- 16642543
TI  - Effects of vitamin K2 on the development of osteopenia in rats as the models of
      osteoporosis.
AB  - Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To
      understand the effects of vitamin K2 on bone mass and bone metabolism, we
      reviewed its effects on the development of osteopenia in rats, which
      characterizes models of osteoporosis. Vitamin K2 was found to attenuate the
      increase in bone resorption and/or maintain bone formation, reduce bone loss,
      protect against the loss of trabecular bone mass and its connectivity, and
      prevent the decrease in strength of the long bone in ovariectomized rats.
      However, combined treatment of bisphosphonates and vitamin K2 had an additive
      effect in preventing the deterioration of the trabecular bone architecture in
      ovariectomized rats, while the combined treatment of raloxifene and vitamin K2
      improved the bone strength of the femoral neck. The use of vitamin K2 alone
      suppressed the increase in trabecular bone turnover and endocortical bone
      resorption, which attenuated the development of cancellous and cortical
      osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the
      decrease in bone formation in prednisolone-treated rats, thereby preventing
      cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2
      suppressed endocortical bone resorption and stimulated bone formation, delaying
      the reduction of the trabecular thickness and retarding the development of
      cortical osteopenia. Vitamin K2 also prevented the acceleration of bone
      resorption and the reduction in bone formation in tail-suspended rats, which
      counteracted cancellous bone loss. Concomitant use of vitamin K2 with a
      bisphosphonate ameliorated the suppression of bone formation and more effectively
      prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated
      renal calcium reabsorption, retarded the increase in serum parathyroid hormone
      levels, and attenuated cortical bone loss primarily by suppressing bone
      resorption in calcium-deficient rats while maintaining the strength of the long
      bone in rats with magnesium deficiency. These findings suggest that vitamin K2
      may not only stimulate bone formation, but may also suppress bone resorption.
      Thus, vitamin K2 could regulate bone metabolism in rats, which represented the
      various models of osteoporosis. However, the effects of vitamin K2 on bone mass
      and bone metabolism seem to be modest.

PMID- 16642544
TI  - Pharmacotherapy for alcohol dependence: anticraving medications for relapse
      prevention.
AB  - Alcohol dependence is a chronic disorder that results from a variety of genetic,
      psychosocial, and environmental factors. Relapse prevention for alcohol
      dependence has traditionally involved psychosocial and psychotherapeutic
      interventions. Pharmacotherapy, however, in conjunction with behavioral therapy,
      is generating interest as another modality to prevent relapse and enhance
      abstinence. Naltrexone and acamprosate are at the forefront of the currently
      available pharmacological options. Naltrexone is an opioid receptor antagonist
      and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes
      the dysregulation of N-methyl-D- aspartate (NMDA)-mediated glutamatergic
      excitation that occurs in alcohol withdrawal and early abstinence. These
      different mechanisms of action and different target neurotransmitter systems may
      endow the two drugs with efficacy for different aspects of alcohol use behavior.
      Since not all patients seem to benefit from naltrexone and acamprosate, there are
      ongoing efforts to improve the treatment outcomes by examining the advantages of
      combined pharmacotherapy and exploring the variables that might predict the
      response of the medications. In addition, novel medications are being
      investigated to assess their efficacy in preventing relapse and increasing
      abstinence.

PMID- 16642545
TI  - A comparative study of magnetic-activated cell sorting, cytotoxicity and
      preplating for the purification of human myoblasts.
AB  - Although cultured myoblast transplantation has been extensively studied as a gene
      complementation approach to muscular dystrophy treatment, clinical success has
      still been limited. The inability to adequately isolate and purify myoblasts
      presents a major limitation to the production of sufficient myoblasts for
      engrafting purposes. This study attempted to purify myoblasts from primary
      culture by magnetic-activated cell sorting (MACS), complement-mediated
      cytotoxicity, and a preplating technique. As a result of positive myoblasts
      selection by MACS, the average percentage of myoblasts in mixed culture was
      increased from 30.0% to 41.7%. We observed both myoblast lysis and fibroblast
      lysis after complement-mediated cytotoxicity. Enrichment of myoblasts in mixed
      culture was found to increase to 83.1% by using the preplating technique. In
      addition, higher purification (92.8%) was achieved by following the preplating
      technique with MACS. Thus, preplating in combination with magnetic-activated cell
      sorting allows for a rapid and effective isolation of myoblasts from human muscle
      tissue.

PMID- 16642546
TI  - Respiratory muscle strength and cough capacity in patients with Duchenne muscular
      dystrophy.
AB  - The function of inspiratory muscles is crucial for effective cough as well as
      expiratory muscles in patients with Duchenne muscular dystrophy (DMD). However,
      there is no report on the correlation between cough and inspiratory muscle
      strength. To investigate the relationships of voluntary cough capacity, assisted
      cough techniques, and inspiratory muscle strength as well as expiratory muscle
      strength in patients with DMD (n= 32). The vital capacity (VC), maximum
      insufflation capacity (MIC), maximal inspiratory pressure (MIP), and maximal
      expiratory pressure (MEP) were measured. Unassisted peak cough flow (UPCF) and
      three different techniques of assisted PCF were evaluated. The mean value of MICs
      (1918 +/- 586 mL) was higher than that of VCs (1474 +/- 632 mL) (p < 0.001). All
      three assisted cough methods showed significantly higher value than unassisted
      method (212 +/- 52 L/min) (F = 66.13, p < 0.001). Combined assisted cough
      technique (both manual and volume assisted PCF; 286 +/- 41 L/min) significantly
      exceeded manual assisted PCF (MPCF; 246 +/- 49 L/ min) and volume assisted PCF
      (VPCF; 252 +/- 45 L/min) (F = 66.13, p < 0.001). MIP (34 +/- 13 cmH2O) correlated
      significantly with both UPCF and all three assisted PCFs as well as MEP (27 +/-
      10 cmH2O) (p < 0.001). Both MEP and MIP, which are the markers of respiratory
      muscle weakness, should be taken into account in the study of cough
      effectiveness.

PMID- 16642547
TI  - Liquid heparin anticoagulant produces more negative bias in the determination of
      ionized magnesium than ionized calcium.
AB  - The ionized calcium level in blood is known to be falsely decreased when self
      prepared liquid heparin anticoagulant is used, due to dilution and binding
      effects. The effect of liquid heparin on the determination of ionized magnesium
      is not as well understood. We compared the effect of liquid sodium heparin on the
      determination of ionized calcium and magnesium in 44 clinical samples using two
      types of user-prepared heparin syringes which differed in the amount of residual
      heparin from the BD Preset reference syringe. With the type 1 syringe, the liquid
      heparin was expelled once or twice such that some heparin could be left in the
      dead space at the syringe hub, while the liquid sodium heparin was thoroughly
      expelled from the type 2 syringe. The ionized magnesium levels obtained with the
      type 1 syringe were significantly lower than the reference value (by 0.068
      mmol/L) (p < 0.0001), while the value obtained with the type 2 syringe differed
      less from the reference, by only 0.014 mmol/L (p < 0.0001). The heparin binding
      effect resulted in more negative bias in ionized magnesium (- 0.026 +/- 0.032
      mmol/L) than in ionized calcium (- 0.009 +/- 0.042 mmol/L, p < 0.0001). In
      conclusion, we recommend using lyophilized, calcium-balanced, heparinized
      syringes for the determination of ionized magnesium and ionized calcium due to
      the increased negative bias in ionized magnesium determinations. When user
      prepared syringes are used, the thorough evacuation of heparin solution should be
      strictly prescribed.

PMID- 16642548
TI  - Plasma factor XIII activity in patients with disseminated intravascular
      coagulation.
AB  - The objective of this study was to investigate the correlation between factor
      XIII (FXIII) activity and disseminated intravascular coagulation (DIC) parameters
      and also to evaluate the clinical usefulness of DIC diagnosis. Citrated plasma
      from eighty patients with potential DIC was analyzed for FXIII activity. The
      primary patient conditions (48 male and 32 female, mean age, 51 years) were
      malignancy (n = 29), infection (n = 25), inflammation (n = 6), heart disease (n=
      3), thrombosis (n = 2), injury (n = 2), and other miscellaneous conditions (n =
      13). FXIII testing was performed using the CoaLinkTM FXIII Incorporation Assay
      Kit (PeopleBio Inc.). Among 80 patients who were suspected to have DIC based on
      clinical analysis, 46 (57.5%) fulfilled the overt DIC criteria (DIC score > = 5)
      according to the International Society of Thrombosis and Haemostasis. FXIII
      levels in the plasma were significantly decreased in overt DIC compared to non
      overt DIC patients (mean 75.1% and 199.7% respectively, p < 0.0001).
      Interestingly, we found a significant inverse correlation between DIC scores and
      FXIII activity. In addition, FXIII activity significantly correlated with other
      hemostatic markers that included platelet count, prothrombin time, activated
      partial thromboplastin time, fibrinogen, and D-dimer. FXIII levels were
      significantly lower in patients with liver or renal dysfunction. In conclusion,
      FXIII cross-linking activity measurements may have differential diagnostic value
      as well as predictive value in patients who are suspected to have DIC.

PMID- 16642549
TI  - Plasma level of IL-6 and its relationship to procoagulant and fibrinolytic
      markers in acute ischemic stroke.
AB  - Procoagulant or impaired fibrinolytic states as well as inflammatory reactions
      mediated by cytokines are likely involved in the pathogenesis of acute ischemic
      stroke. We examined the potential relationship between interleukin 6 (IL-6) and
      hemostatic markers. The procoagulant and fibrinolytic states were assessed in 46
      patients with acute stroke by measuring plasma levels of plasminogen activator
      inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and plasminogen
      antiplasmin complex (PAP). Circulating IL-6 levels were measured using ELISA
      (Quantikine, R and D systems, MN, USA). Circulating IL-6 (mean, 26.5 pg/mL) and
      PAI-1 (mean, 19.9 ng/mL) levels were higher in patients with acute stroke than in
      healthy subjects (mean, 3.0 pg/mL, 10.4 ng/mL, respectively). TAT levels were
      statistically different according to the etiologic subtypes of stroke
      (atherogenic, 2.5 ng/mL; lacunar 3.2 ng/mL; cardiogenic 9.9 ng/mL, p = 0.021).
      Neither procoagulant levels nor fibrinolytic markers significantly correlated
      with circulating IL-6 levels. Our findings suggest that elevated proinflammatory
      cytokines during the initial hours of ischemic stroke may be an independent
      pathogenic factor or a consequence of the thrombotic event with no relationship
      to the procoagulant or fibrinolytic states.

PMID- 16642550
TI  - Calcium uptake and release through sarcoplasmic reticulum in the inferior oblique
      muscles of patients with inferior oblique overaction.
AB  - We characterized and compared the characteristics of Ca2+ movements through the
      sarcoplasmic reticulum of inferior oblique muscles in the various conditions
      including primary inferior oblique overaction (IOOA), secondary IOOA, and
      controls, so as to further understand the pathogenesis of primary IOOA. Of 15
      specimens obtained through inferior oblique myectomy, six were from primary IOOA,
      6 from secondary IOOA, and the remaining 3 were controls from enucleated eyes.
      Ryanodine binding assays were performed, and Ca2+ uptake rates, calsequestrins
      and SERCA levels were determined. Ryanodine bindings and sarcoplasmic reticulum
      Ca2+ uptake rates were significantly decreased in primary IOOA (p < 0.05).
      Western blot analysis conducted to quantify calsequestrins and SERCA, found no
      significant difference between primary IOOA, secondary IOOA, and the controls.
      Increased intracellular Ca2+ concentration due to reduced sarcoplasmic reticulum
      Ca2+ uptake may play a role in primary IOOA.

PMID- 16642551
TI  - In vitro and in vivo effect of parathyroid hormone analogue (1-14) containing 
      amino-iso-butyric acid residue (Aib)1,3.
AB  - Firstly, parathyroid hormone (1-14) [PTH (1-14)] analogue containing various 
      amino-iso-butyric acid residue (Aib) was synthesized by exchanging the 1st and
      3rd Ala residues of alpha carbon of PTH (1-14). This analogue revealed to have
      the quite tight and stable -helical structure using the nuclear magnetic
      resonance (NMR) analysis. The biological activities of these analogues were
      examined using a cAMP- generating assay in LLC-PK1 cell lines stably transfected
      with the wild- type human PTH1 receptor. Only the PTH analogue substituted with
      methyl moiety without acetylation showed significant cAMP generating action with
      15.0 +/- 3.414 of EC50. Then, we used an ovariectomized rat model system to
      compare the in vivo effects of parathyroid hormone analogue with that of PTH (1
      84). Daily subcutaneous administration of the unacetylated Aib1,3PTH (1-14) for 5
      weeks in 30 nM/kg subcutaneously with positive control group receiving PTH (1-84)
      with 8 nM/ kg were performed. However, there was no significant change in spinal
      or femoral bone mineral density assessed by dual x-ray absorptiometry (DXA) in
      the Aib1,3PTH (1-14) group where definite increase of these parameters shown in
      the PTH (1-84) group (p < 0.001). Assessment of bone strength was evaluated with
      no significant differences among all groups. It was quite disappointing to see
      the actual discrepancies between the result of significant pharmacokinetic
      potency and the in vivo clinical effect of the Aib1,3PTH (1-14). However, there
      are several limitations to mention, such as the short duration of treatment,
      matter of dosage, and insufficient effect of tight -helical structures with
      absence of C-terminus. In conclusion, our findings suggest that unacetylated
      Aib1,3PTH (1-14) did not exhibit any anabolic effects at the bones of
      ovariectomized rats.

PMID- 16642552
TI  - Generation of nitric oxide in the opossum lower esophageal sphincter during
      physiological experimentation.
AB  - Lipopolysaccharide (LPS), given in vivo, modulates opossum esophageal motor
      functions by inducing the inducible nitric oxide synthase (iNOS), which increases
      nitric oxide (NO) production. Superoxide, a NO scavenger, is generated during
      this endotoxemia. Superoxide is cleared by superoxide dismutase (SOD) and
      catalase (CAT) to protect the physiological function of NO. This study examined
      whether lower esophageal sphincter (LES) motility, NO release, and iNOS and
      nitrotyrosine accumulation in the LES are affected by LPS in vitro. Muscle strips
      from the opossum LES were placed in tissue baths containing oxygenated Krebs
      buffer. NO release was measured with a chemiluminescence NOx analyzer, and
      Western blots were performed to analyze iNOS and nitrotyrosine production. The
      percent change in resting LES tone after a 6-hour exposure to LPS was
      significantly increased compared to pretreatment values. The percent LES
      relaxation upon electrical stimulation was significantly decreased in the control
      group at 6 hours, indicating that the LPS treatment had an effect. The NO
      concentration in the tissue bath of LPS- treated muscle without nerve stimulation
      was significantly less than that of LPS treatment combined with SOD/CAT or
      SOD/CAT alone. iNOS and nitrotyrosine were detectable and increased over time in
      the LES muscle of both the control and LPS-treated groups. Antioxidant enzymes
      may play a role in regulating NO-mediated neuromuscular functions in the LES.

PMID- 16642553
TI  - Clinical results of minimally invasive open-heart surgery in patients with mitral
      valve disease: comparison of parasternal and low-sternal approach.
AB  - Clinical results of minimally invasive mitral valve surgery were retrospectively
      reviewed, and two different surgical approaches were compared in this study.
      Between 1997 and 2004, a total of 86 patients with mitral valve disease underwent
      minimally invasive surgery at the Yonsei University Cardiovascular Center. Age of
      patients averaged 41.6 +/- 14.0 years and 69 patients were female. Surgical
      approach included low- sternal incisions with mini-sternotomy, and right
      parasternal or thoracotomy approach. Either direct aortic or femoral arterial and
      bicaval cannulations were used in all patients. Patients were divided into two
      groups according to the method of surgical approach (parasternal (P) vs low
      sternal (L)), and the results were compared. Postoperative NYHA functional class
      improved to 1.1 +/- 0.4 in all patients (no significant statistical difference
      between two groups). Mean wound length (P: 9.21 +/- 1.10 vs L: 11.24 +/- 0.82 cm,
      p < 0.05), and mechanical ventilation time (P: 10.42 +/- 4.36 vs L: 12.90 +/-
      5.00 min, p=0.04) was significantly shorter in parasternal group, and mean
      operation time(P:294.74 +/- 59.41 vs. L:259.31 +/- 54.36 min, p=0.03) was
      significantly shorter in low-sternal group. Mean cardiopulmonary bypass time, and
      aortic cross clamp time was also shorter in low-sternal group without statistical
      difference. There were 2 minor wound complications in all patients (p=NS), and no
      hospital death. Comparing the two different surgical approach of minimally
      invasive mitral valve surgery, parasternal approach is thought to be more
      beneficial in reducing postoperative scar, and intubation time.

PMID- 16642554
TI  - Comparison of the ratio of upper to lower chest wall in children with spastic
      quadriplegic cerebral palsy and normally developed children.
AB  - The upper chest wall does not grow properly in children with spinal muscular
      atrophy (SMA) with paradoxical breathing. This suggests that long-term inability
      to take a deep breath in developing children may result in underdevelopment of
      the upper chest wall. In addition, a rapid and paradoxical breathing pattern is
      frequently observed in children with severe cerebral palsy (CP), which often
      corresponds to the underdevelopment of the upper chest wall. The present study is
      designed to evaluate the ratio of the upper to lower chest wall in children with
      severe spastic quadriplegic CP, compared with normal children. We compared normal
      children with children that had spastic quadriplegic CP who did not have kyphosis
      or scoliosis. Test subjects were matched in terms of age, height, and weight. The
      diameters of upper chest (D(apex)) and of lower chest (D(base)) were measured on
      the anteroposterior (AP) view of a chest X-ray and the D(apex) to D(base) ratio
      was calculated. In selected cases the forced vital capacity (FVC) was measured
      using a Wright Respirometer. The D(apex) to D(base) ratio was significantly lower
      in the CP group than in the control group (p < 0.001). The ratio increased
      linearly with age (p < 0.001) in both CP (R = 0.372) and control groups (R =
      0.477). The FVC/preFVC showed significant correlation with the D(apex) to D(base)
      ratio (R = 0.542, p < 0.01). The results of this study suggest a deviation of
      optimal chest wall structure in children with spastic quadriplegic CP.

PMID- 16642555
TI  - The relationship of anatomic variation of pancreatic ductal system and
      pancreaticobiliary diseases.
AB  - The aims of this study were to identify the morphological diversities and
      anatomical variations of pancreatic ductal system and to define the relationships
      between pancreatic ductal systems, pancreaticobiliary diseases, and procedure-
      related complications, including post-ERCP pancreatitis. This study included 582
      patients in whom both pancreatic duct (PD) and common bile duct were clearly
      visible by ERCP. PD systems were categorized into four types according to the
      relationship between common bile duct and PD. In types A and B, Wirsung duct
      formed the main PD. In type C, Wirsung duct did not form the main PD. If PD
      system did not fall into any of these three types, it was categorized as type D.
      The distribution of types among pancreatic ducts examined was as follows: type A:
      491 cases (84.4%), type B: 56 cases (9.6%), type C: 20 cases (3.4%), and type D:
      15 cases (2.6%). The anomalous anatomic variations of PD systems were divided
      into migration, fusion, and duplication anomalies. PD anomalies were noted in 51
      patients, of which 19 (3.3%) were fusion anomalies (12 complete pancreas divisum,
      7 incomplete pancreas divisum), and 32 (5.5%) were duplication anomalies (5
      number variations, 27 form variations). No significant relationships between
      various PD morphologies and pancreaticobiliary diseases were found. However, post
      ERCP hyperamylasemia was more frequently found in types C (41.7%), D (50%) and A
      (19.8%) than in type B (9.4%). In summary, whether Wirsung duct forms the main PD
      and the presence or absence of the opening of the Santorini duct are both
      important factors in determining the development of pancreatitis and
      hyperamylasemia after ERCP.

PMID- 16642556
TI  - Elevated contractile responses to acetylcholine in organ cultured rabbit carotid
      artery.
AB  - The aim of the present study was to examine the functional changes that occur
      when a rabbit carotid artery is cultured in serum-free medium. In endothelium
      (EC)-intact arteries cultured under serum-free conditions, acetylcholine (ACh)
      induced relaxation responses were partially, yet significantly, reduced when
      compared with freshly isolated arteries. After pretreatment with NG-nitro-L
      arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, application of
      ACh resulted in a significant contraction in organ cultured arteries. The
      amplitude of the ACh-induced contractions increased with the duration of culture.
      In EC-denuded arteries cultured under serum-free conditions, ACh induced
      responses similar to those in EC-intact arteries pretreated with L-NAME.
      Furthermore, ACh caused a significant increase in intracellular Ca2+
      concentration ([Ca2+]i) in EC-denuded arteries cultured under serum-free
      condition for 7 days. There was little change in either [Ca2+]i or tension in
      freshly isolated carotid rings. There was no difference in sodium nitroprusside
      induced relaxation responses between fresh and cultured arteries. These results
      suggest that prolonged culture of carotid arteries under serum- free conditions
      changes the functional properties of vascular reactivity in rabbit carotid
      arteries.

PMID- 16642557
TI  - A case report of familial benign hypocalciuric hypercalcemia: a mutation in the
      calcium-sensing receptor gene.
AB  - Familial benign hypocalciuric hypercalcemia (FBHH) is an autosomal dominant trait
      with high penetrance, clinically manifesting a relatively benign, lifelong,
      persistent hypercalcemia and hypocalciuria without hypercalcemic related
      complications. The calcium-sensing receptor (CaSR) plays an important role in the
      regulation of PTH secretion and calcium metabolism. Here we present a family with
      FBHH of an autosomal dominant inheritance. A heterozygous mutation of E297K (GAG 
      -> AAG, exon 4) of CaSR gene was found in 3 family members. To our knowledge, it
      is the first confirmed case of FBHH with CaSR gene mutation in Korea.

PMID- 16642558
TI  - Metaplastic carcinoma with extensive chondroid differentiation in the breast
      (chondroid carcinoma).
AB  - Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with
      chondroid differentiation is even rarer. Here, we report a case of metaplastic
      carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that
      was challenging to diagnose. The tumor was characterized by an abundant
      chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma
      was minimal. The peripheral portion of the tumor showed increased cellularity
      with pleomorphism and definitive invasive growth. Tumor cells in the
      chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy
      positive for cytokeratin, but negative for epithelial membrane antigen (EMA).
      Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100
      protein, and patchy positive for EMA. In both areas, tumor cells were negative
      for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed.
      When pathologists encounter breast tumors with chondroid differentiation, careful
      sampling and immunohistochemistry for cytokeratin and SMA are most helpful to
      differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant
      adenomyoepithelioma.

PMID- 16642559
TI  - Intraosseous nerve sheath tumors in the jaws.
AB  - Although the head and neck region is recognized as the most common location for
      peripheral nerve sheath tumors, central involvement, particularly in the jaw
      bones, is quite unusual. Neurofibroma is one of the most common nerve sheath
      tumors occurring in the soft tissue and generally appears in neurofibromatosis 1
      (NF1 or von Recklinghausen's disease). Malignant peripheral nerve sheath tumors
      (MPNSTs) are uncommon sarcomas that almost always arise in the soft tissue. Here,
      we report four cases of intraosseous peripheral nerve sheath tumors occurring in
      the jaw bones and compare the clinical, radiologic, and pathologic findings in
      order to make a differential diagnosis.

PMID- 16642560
TI  - Reperfusion pulmonary edema after the removal of hepatocellular carcinoma
      embolus.
AB  - To report a non-fatal case of reperfusion pulmonary edema (RPE) after the removal
      of a hepatocellular carcinoma embolus, which had caused an acute obstruction of
      the tricuspid valve and pulmonary vasculature during a hepatic lobectomy.
      Pulmonary embolism caused by hepatocellular carcinoma embolus is extremely rare,
      and, in the present case, it was associated with unusual clinical features. A 69
      year-old ASA II woman with hepatocellular carcinoma was presented for an elective
      left hepatic lobectomy. During the surgery, the tumor embolus was dislodged from
      the interior of the lumen of the inferior vena cava (IVC), which then drifted
      into the tricuspid valve area and pulmonary vasculature. The patient showed the
      specific signs of acute pulmonary embolism, such as a reduction in end-tidal
      carbon dioxide, an increase in central venous pressure, and a decrease in
      arterial pressure. The patient exhibited the symptoms for about 10 minutes. After
      this period, however, cardiovascular variables became relatively stable, even
      during a mechanical obstruction due to cross-clamping the pulmonary artery for
      embolectomy. After several hours of pulmonary embolectomy, the patient
      experienced an episode of RPE. The ventilatory supports for the treatment of RPE
      were successful, and the patient recovered without any complications. The
      patient's case in the present study demonstrates that pulmonary embolism may
      occur as a result of a hepatocellular carcinoma extending into the IVC during
      operative management. The anesthesiologist should be careful of the possibilities
      of RPE after removal of the tumor embolus.

PMID- 16642561
TI  - Acute upper gastrointestinal bleeding due to metastatic lung cancer: an unusual
      case.
AB  - There have been several published reports on metastatic lesions in the stomach,
      but the number of cases have been limited due to the low frequency of the
      condition. Metastatic lesions in the stomach are usually asymptomatic. A 55-year
      old man with known metastatic lung adenocancer exhibited epigastric pain,
      hematemesis, and melena. A bleeding, ulcerated gastric metastasis was found and
      treated with endoscopic therapy and omeprazole.

PMID- 16642562
TI  - Transition from pemphigus foliaceus to pemphigus vulgaris: case report with
      literature review.
AB  - The transition between the main subtypes of pemphigus, pemphigus vulgaris (PV),
      and pemphigus foliaceus (PF) has rarely been reported. Moreover, the development
      of PV in a patient with PF is much more unusual than that of PF in a patient with
      PV. We report a 48-year-old man who presented with cutaneous lesions showing the
      typical clinical and histological features of PF. Five years later, his skin
      lesions became extensive and he developed oral erosions. His condition did not
      respond well to steroids and azathioprine. Histological examination of a vesicle
      disclosed suprabasal acantholysis in contrast to the subcorneal acantholysis
      discovered upon initial histological evaluation. Indirect immunofluorescence
      revealed IgG antikeratinocyte cell surface antibodies at a titer of 1:640. The
      titer was 1:160 at initial diagnosis. Upon immunoblotting, the patient's serum
      reacted with 130 kiloDalton (kDa) and 160 kDa proteins, suggesting desmoglein
      (Dsg) 3 and 1, respectively. We herein report an unusual case of PV that
      developed from PF during the disease's flare-up.

PMID- 16642563
TI  - HIV-specific cellular immune responses are stimulated by structured treatment
      interruption in chronically HIV-1 infected Koreans.
AB  - We evaluated the enhancing effect of structured treatment interruptions (STIs) on
      HIV-specific immunity in chronically HIV-1 infected Korean patients. A
      prospective case-control study was done with a total of 10 subjects for a period
      of 26 weeks. Six subjects were on STIs and four subjects were on continuous HAART
      for comparison. The STI subjects underwent four periods of STIs. For those on
      STIs, HAART was stopped at week 0 for two weeks, and resumed thereafter for six
      weeks. Viral load and CD4+/CD8+ T cells were measured by HIV RNA RT-PCR and flow
      cytometry, and HIV-specific immunity was measured by an ELISPOT assay. HIV
      specific cytotoxic T cell immunity was more pronounced in the STI subjects than
      in the continuous HAART subjects after 26 weeks (p = 0.011). The difference in
      cytotoxic T cell response in the STI group was more prominent than in the
      continuous HAART group (p = 0.011). Viral load after 26 weeks was higher in the
      STI subjects than in the continuous HAART subjects (p = 0.008). An HIV-specific
      cellular immune response can be stimulated by STIs in chronically HIV-infected
      Koreans. A larger study is warranted in order to further characterize viral and
      immunological parameters of treatment with STIs in cases of chronic HIV
      infection.

PMID- 16642564
TI  - Evidence that amphotericin B mediates reactivation of latent Epstein-Barr virus
      in Hodgkin's lymphoma allowing cytotoxicity by acyclovir.
AB  - This brief communication focuses on aspects of a recent case report (Yonsei Med J
      2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL)
      after a single day of chemotherapy. A septic episode required stopping
      chemotherapy and starting amphotericin B and acyclovir. Remission evidence was
      seen within days of starting these. A review of research supporting the notion
      that amphotericin B can reactivate latent Epstein-Barr virus and thus allow
      acyclovir to kill infected HL cells is given. Experimental work is required to
      confirm or refute this possibility. If successful, amphotericin B and acyclovir
      treatment could be extended to other EBV-driven cancers such as Burkitt's
      lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial
      cancer of the breast, colon, prostate, and others.

PMID- 16642566
TI  - How your brother's or sister's heart health may link to yours.

PMID- 16642565
TI  - Retraction: cortical margining capabilities of fins associated with ventral
      cervical spine instrumentation.

PMID- 16642567
TI  - Despite risks, aggressive treatment appears to pay off.

PMID- 16642568
TI  - The son of a friend of mine recently had a heart attack at age 40. He was in good
      shape and passed a physical exam a few months ago. It's shaken my faith that
      we're making progress against heart disease. How rare are cases like this.

PMID- 16642569
TI  - My doctors were concerned that I had abnormal troponin levels and cardiac
      symptoms. Prior to a coronary angiogram, I was given an intravenous dose of
      heparin, and now take a beta-blocker, metoprolol, 12.5 milligrams twice a day. I
      bleed a lot and bruise when I have a cut or a contusion. Why?

PMID- 16642570
TI  - Testing your diagnostic skills. Case no. 2: melanotic macule.

PMID- 16642571
TI  - Outcome measurement in dysphagia: not so hard to swallow.
AB  - This article reports on the use of a new tool from the Australian Therapy Outcome
      Measures (AusTOMs) set--the Swallowing scale. The scale is one of six, designed
      to measure outcomes of clients attending speech pathology practices in Australia.
      The tool was used for six months in clinical practices across 14 healthcare sites
      in Victoria, Australia (including six acute hospitals, six rehabilitation
      services, one specialist pediatric hospital, and one specialist cancer
      institute). This article provides preliminary descriptive data and analyses of
      outcomes from swallowing therapy, along with discussion of the strengths and
      weaknesses of this tool. Potential clinical applications are suggested.

PMID- 16642572
TI  - Guest workers being exploited in ACT hospitality industry.

PMID- 16642573
TI  - Impacts of population growth and economic development on the nitrogen cycle:
      consequences and mitigation at local, regional and global scales. Proceedings
      from the 3rd International Nitrogen Conference (N2004), Nanjing, China, October
      12-16, 2004.

PMID- 16642574
TI  - Digestive Disease Week and the 107th Annual Meeting of the American
      Gastroenterological Association Institute, May 20-25, 2006, Los Angeles,
      California, USA. Abstracts.

PMID- 16642575
TI  - Potential mechanisms of improvement of airway hyperresponsiveness by inhaled
      corticosteroid therapy in asthmatic patients.
AB  - OBJECTIVE: Recent clinical trials with administration of IL-5 antibodies to
      asthmatic patients have revealed reduction of eosinophilia but unaltered airway
      hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy
      eliminates both eosinophilia and AHR. This study was designed to examine the
      mechanisms by which ICS improves airway hyperresponsiveness in asthmatic
      patients. METHODS: Clinical variables of asthma involving vascular permeability
      and IL-5 levels were examined in 23 asthmatic patients and 11 normal control
      subjects. After the first sputum induction, inhaled beclomethasone dipropionate
      (BDP 800 microg/day) was administered to asthmatic patients for 8 weeks, and
      sputum induction was repeated. RESULTS: IL-5 levels in induced sputum and airway
      vascular permeability index were significantly higher in asthmatic patients. IL-5
      was positively correlated with percentage of eosinophils in induced sputum, and
      negatively correlated with FEV1, but not correlated with PC20 methacholine. After
      BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to
      the same levels as in normal subjects. Conversely, PC20 methacholine and airway
      vascular permeability did not improve to the same levels as in normal subjects.
      Increase in PC20 methacholine from before to after BDP therapy was significantly
      correlated with decrease in airway permeability index, but not with decrease in
      IL-5 level. CONCLUSION: Our results suggest a clear dissociation between IL-5 and
      AHR. ICS therapy improves AHR at least in part through decrease in airway
      vascular permeability.

PMID- 16642576
TI  - Universal stem cell principles proposed: rules would guide research efforts.

PMID- 16642577
TI  - Scientist rebels against WHO over bird flu.

PMID- 16642578
TI  - Use of substitution for blood draws ethics challenge.

PMID- 16642579
TI  - British rethinking test rules after drug trial nearly kills 6.

PMID- 16642580
TI  - Abstracts of the 83rd Annual Meeting of the Physiological Society of Japan, March
      28-30, 2006, Maebashi, Japan.

PMID- 16642581
TI  - The Diabetes Management Team. Abstracts of the 12th Annual International
      Conference of the UDOP, CFNI, UWISON. March 2-5, 2006, Ocho Rios, Jamaica.

PMID- 16642582
TI  - Abstracts of the 2006 AAHPERD National Convention, Salt Lake City, Utah, USA,
      April 2005.

PMID- 16642583
TI  - Clozapine alone versus clozapine and risperidone for refractory schizophrenia.

PMID- 16642584
TI  - Doctor in India jailed for telling sex of a fetus.

PMID- 16642585
TI  - South Dakota bans abortion, setting up a battle.

PMID- 16642586
TI  - Guidant consultant advised company to release data on defects.

PMID- 16642587
TI  - Clozapine alone versus clozapine and risperidone for refractory schizophrenia.

PMID- 16642588
TI  - State still confines mentally ill in nursing homes, suit says.

PMID- 16642589
TI  - Government health researchers pressed to share data at no charge.

PMID- 16642590
TI  - Hypertonic saline for cystic fibrosis.

PMID- 16642591
TI  - Hypertonic saline for cystic fibrosis.

PMID- 16642592
TI  - Unprofessional behavior among medical students.

PMID- 16642593
TI  - Unprofessional behavior among medical students.

PMID- 16642594
TI  - Unprofessional behavior among medical students.

PMID- 16642595
TI  - Preventing nephropathy induced by contrast medium.

PMID- 16642596
TI  - Preventing nephropathy induced by contrast medium.

PMID- 16642597
TI  - Salient findings: summaries of key findings in the research literature.

PMID- 16642598
TI  - Medical imaging in focus.

PMID- 16642599
TI  - The first day of class: breaking the ice.

PMID- 16642600
TI  - NSAID-induced acute phase response is due to increased intestinal permeability
      and characterized by early and consistent alterations in hepatic gene expression.
AB  - Toxicogenomics using a reference database can provide a better understanding and
      prediction of toxicity, largely by creating biomarkers that tie gene expression
      to actual pathology events. During the course of building a toxicogenomic
      database, an observation was made that a number of non-steroidal anti
      inflammatory compounds (NSAIDs) at supra-pharmacologic doses induced an acute
      phase response (APR) and displayed hepatic gene expression patterns similar to
      that of intravenous lipopolysaccharide (LPS). Since NSAIDs are known to cause
      injury along the gastrointestinal tract, it has been suggested that NSAIDs
      increase intestinal permeability, allowing LPS and/or bacteria into the systemic
      circulation and stimulating an APR detectable in the liver. A short term study
      was subsequently conducted examining the effects of aspirin, indomethacin,
      ibuprofen, and rofecoxib to rats and a variety of endpoints were examined that
      included serum levels of inflammatory cytokines, histologic evaluation, and
      hepatic gene expression. Both indomethacin and ibuprofen injured the
      gastrointestinal tract, induced an APR, and increased serum levels of LPS, while
      rofecoxib and aspirin did not affect the GI tract or induce an APR. In treatments
      that eventually showed a systemic inflammatory response, hepatic expression of
      many inflammatory genes was noted as early as 6 hours after treatment well before
      alterations in traditional clinical pathology markers were detected. This finding
      led to the creation of a hepatic gene expression biomarker of APR that was
      effectively shown to be an early identifier of imminent inflammatory injury. In
      terms of the relative gastrointestinal safety and the NSAIDs studied, an
      important safety distinction can be made between the presumptive efficacious dose
      and the APR-inducing dose for indomethacin (1-2-fold), ibuprofen (5-fold), and
      rofecoxib (approximately 250-fold). Our data support the notion that NSAID
      induced intestinal injury results in leakage of commensural bacteria and/or LPS
      into the circulation, provoking a systemic inflammatory response and that hepatic
      gene expression-based biomarkers can be used as early and sensitive biomarkers of
      APR onset.

PMID- 16642601
TI  - Intracranial penetration.

PMID- 16642602
TI  - [12th Congress of the Association of Allergy and Clinical Immunology of Serbia
      and Montenegro, Niska Banja. 27-30 September 2004] ].

PMID- 16642603
TI  - [Problems and countermeasures for development of acupuncture and moxibustion
      sciences].
AB  - It is the problems facing acupuncture and moxibustion medicines in our country
      that the course of modernization has a tendency to deviating guidance of TCM
      theories; the course of internalization lacks legislative guarantee; the kinds of
      diseases treated decrease year by year; professional structures shrink, with
      lower therapeutic fee, and acupuncture and moxibustion are divorced from each
      other, making it develop slowly; income of acupuncturists is low so as to a large
      number of talent outflow; international talent for acupuncture and moxibustion
      lack systematical and scientific training. Therefore, you should grasp the
      development opportunity of internalization of acupuncture and moxibustion, taking
      difficult and complicated diseases as focal point, develop scientific studies of
      standardization, further increasing therapeutic effects, and increasing
      investment and training of talents, and other measures for strengthening
      construction of acupuncture and moxibustion sciences.

PMID- 16642604
TI  - [Observation on therapeutic effect of electroacupuncture at points Baliao and
      Huiyang (BL 35) on retention of urine induced by spinal cord injury].
AB  - OBJECTIVE: To explore a more effective therapy for retention of urine induced by
      spinal cord injury. METHODS: Eighty-four cases were randomly divided into a
      treatment group of 46 cases and a control group of 38 cases. The treatment group
      were treated with electroacupuncture at Baliao and Huiyang (BL 35), and the
      control group with electroacupuncture at acupoints routinely selected. RESULTS:
      The total effective rate and the cured rate were 82.6% and 43.5% in the treatment
      group and 63.2% and 23.7% in the control group respectively, with a very
      significant difference between the two groups (P < 0. 01). CONCLUSION:
      Electroacupuncture at Baliao and Huiyang (BL 35) has obvious therapeutic effect
      on retention of urine induced by spinal cord injury.

PMID- 16642605
TI  - [Effects of head point-through-point electroacupuncture on SOD and LPO in the
      patient of Parkinson's disease].
AB  - OBJECTIVE: To observe clinical therapeutic effect of head point-through-point
      electroacupuncture on Parkinson's disease and the mechanism. METHODS: Seventy-six
      cases of Parkinson's disease were randomly divided into a treatment group (n=37)
      treated with head point-through-point electroacupuncture and oral administration
      of madopa, and a control group (n=39) with only oral administration of madopa.
      Superoxide dismutase (SOD) and lipids peroxides (LPO) were determined before and
      after treatment. RESULTS: The effective rate was 97.3% in the treatment group and
      61.5% in the control group with a very significant difference between the two
      groups (P < 0.01). SOD activity and LPO content were significantly improved after
      treatment in the treatment group (P < 0.01), with a significant difference
      between the two groups (P < 0.01). CONCLUSION: Head point-through-point
      electroacupuncture can improve SOD activity and LPO content in the body so as to
      cure Parkinson's disease.

PMID- 16642606
TI  - [Clinical study and acoustical analysis for submucosa hemorrhage of vocal cords
      treated mainly with acupuncture at "Kaiyin point no. 1"].
AB  - OBJECTIVE: To evaluate therapeutic effect of acupuncture at "Kaiyin point No. 1"
      on submucosal hemorrage of vocal cords. METHODS: One hundred and sixty cases were
      randomly divided into a test group and a control group. The test group were
      treated by acupuncture at "Kaiyin point No. 1" with reducing method in
      reinforcing or reducing method by manipulating the needle in cooperation with the
      patient's respiration, combined with deep respiratory movement of the glottis
      laryngeal cavity, once daily; and the control group by spray inhalation of
      western medicine, once daily, 7 days constituting one therapeutic course.
      RESULTS: The cured and markedly effective rate and the total effective rate were
      85.0% and 97.5% in the test group and 60.0% and 85.0% in the control group
      respectively, with a significant difference between the two groups. After
      treatment of the test group,the acoustical parameters maximum phonation time
      (MPT), frequency perturbation quotient (FPQ), amplitude perturbation quotient
      (APQ), ratio of harmonic to noise (H/N) objectively reflected improvement of
      voice quality. CONCLUSION: Acupuncture at "Kaiyin point No. 1" as main method is
      an ideal therapy for submucosa hemorrhage of vocal cords.

PMID- 16642607
TI  - [Clinical observation on effect of acupuncture on nervous functions of the
      patient after operation of. hypertensive cerebral hemorrhage].
AB  - OBJECTIVE: To probe the best therapy for the patient after operation of
      hypertensive cerebral hemorrhage. METHODS: One hundred cases were randomly
      divided into a treatment group and a control group, 50 cases in each group. The
      control group were treated by routine western medicine (Mannitol, Nifedipine and
      Caftriaxone sodium and so On), and the treatment group by the medication of the
      control group plus acupuncture 9 days after operation. Acupuncture was given at
      Neiguan (PC 6), Shuigou (GV 26), Sanyinjiso (SP 6), Jiquan (HT 1) and Weizhong
      (BL 40) and so on, combined with scalp acupuncture, with "restoring consciousness
      and inducing consciousness" needling method, for 10 days. The nervous function
      defect was assessed by Chinese Stroke Scale and the criteria for assessment of
      therapeutic effects. RESULTS: Acupuncture could improve significantly nervous
      function defect. The total effective rate was 86.000 in the treatment group and
      14.0% in the control group with a significant difference between the two groups
      (P < 0.01). CONCLUSION: The therapeutic effect of the treatment group is better
      than that of the control group. Acupuncture combined with western medicine has
      cooperation for treatment of hypertensive intracerebral hemorrhage with a better
      therapeutic effect.

PMID- 16642608
TI  - [Clinical observation on electric stimulation of Yongquan (KI 1) for prevention
      of nausea and vomiting induced by Cisplatin].
AB  - OBJECTIVE: To search for an effective method for controlling nausea and vomiting
      induced by chemotherapy. METHODS: Eighty-eight cases of hepatic cancer with
      interventional therapy of Cisplatin were randomly divided into a treatment group
      and a control group, 44 cases in each group. The treatment group were treated
      with an antiemetic and electroacupuncture at Yongquan (KI 1), and the control
      group only with the antiementic. The controlling rates for nausea and vomiting
      were compared between the two groups. RESULTS: The controlling rates for acute
      nausea, vomiting and delayed vomiting in the treatment group were better than
      those in the control group (P < 0.05). CONCLUSION: Electroacupuncture at Yongquan
      (KI 1) can better prevent and improve the symptoms of nausea and vomiting in the
      patient with chemotherapy of Cisplatin.

PMID- 16642609
TI  - [Clinical observation on acupuncture combined with Xingnaojing injection for
      treatment of cerebral hemorrhage at acute stage].
AB  - OBJECTIVE: To observe therapeutic effects of different therapies on intracerebral
      hemorrhage at acute stage. METHODS: One hundred and twenty-five cases of
      intracerebral hemorrhage at acute stage were randomly divided into a combined
      treatment group, an acupuncture group, a Xingnaojing group and a routine
      treatment group, and effects of different treatment programs on the hematoma
      absorption velocity and nervous function defect scores were observed. RESULTS:
      All of the treatment groups have obvious therapeutic effects for hematoma
      absorption and nervous function defect score, with the best therapeutic effect in
      the combined treatment group (P < 0.01, P < 0.05). CONCLUSION: Acupuncture
      combined with Xingnaojing injectio is an effective therapy for intracerebral
      hemorrhage at acute stage.

PMID- 16642610
TI  - [Comparison of therapeutic effects of deep needling and shallow needling on
      sudden deafness].
AB  - OBJECTIVE: To explore and evaluate therapeutic effect of different needling
      methods on sudden deafness. METHODS: Forty-seven cases were randomly divided into
      a treatment group of 23 cases who were treated by deep needling at Ermen (TE 21),
      Tinggong (SI 19) and Tinghui (GB 2) combined with body acupuncture, and a control
      group of 24 cases who were treated with shallow needling at these acupoints
      combined with body acupuncture. Changes of hearing at different stages after
      treatment were observed and compared between the two groups. RESULTS: The
      effective rate was 87.0% in the treatment group and 29.2% in the control group,
      with a significant difference between the two groups (P < 0.05). CONCLUSION: The
      therapeutic effect of the deep needling group is better than that of the shallow
      needling group.

PMID- 16642611
TI  - [Clinical application of electroacupuncture plus chinese medicine in treatment of
      peripheral facial paralysis].
AB  - OBJECTIVE: To probe into the role of electroacupuncture in treatment of
      peripheral facial paralysis. METHODS: Eighty-six cases were divided into a
      treatment group (n=45) treated with electroacupuncture plus Chinese medicine, and
      a control group (n=41) treated with acupuncture plus Chinese medicine. Taiyang
      (EX-HN 5), Yangbai (GB 14) and other points on the affected side were selected
      and Chinese medicine modified Qianzheng powder was administrated. Their clinical
      therapeutic effects were analyzed and evaluated. RESULTS: The effective rate was
      97. 8% in the treatment group and 82.9% in the control group with a significant
      difference between the two groups (P < 0.05). the treatment group being higher
      than the control group. CONCLUSION: Chinese medicine plus acupuncture combined
      with electroacupuncture has a better therapeutic effect on peripheral facial
      paralysis.

PMID- 16642612
TI  - [Clinical observation on acupoint catgut embedding therapy for treatment of
      ulcerative colitis].
AB  - OBJECTIVE: To compare therapeutic effects of acupoint catgut embedding therapy
      and western medicine on ulcerative colitis. METHODS: One hundred and sixteen
      cases of ulcerative colitis were randomly divided into a treatment group and a
      control group. The treatment group of 56 cases were treated with catgut embedding
      at Dachangshu (BL 25), Zusanli (ST 36), Shangjuxu (ST 37) and other points, and
      the control group with oral administration of salicylazosul-fapyridine, 4-6
      g/day. The therapeutic effects and improvement of symptoms were evaluated by
      reexamination of endoscopy before and 4 weeks, 6-8 weeks after treatment in the
      two groups, and changes of stool property and abdominal pain were compared.
      RESULTS: The short-term therapeutic effect and the long-term therapeutic effect
      of the treatment group were better than those of the control group. CONCLUSION:
      Acupoint catgut embedding therapy has a better therapeutic effect on ulcerative
      colitis with less adverse reactions.

PMID- 16642613
TI  - [Observation on therapeutic effect of acupoint catgut embedding therapy on
      premenstrual syndrome].
AB  - OBJECTIVE: To compare clinical therapeutic effects of acupoint catgut embedding
      therapy and medicine on premenstrual syndrome, so as to search for the best
      method for this disease. METHODS: Eighty-eight cases were randomly divided into a
      catgut embedding group and a medication group. The catgut embedding group were
      treated with main points, Neiguan (PC 6), Sanyinjiso (SP 6), Danzhong (CV 17),
      Guanyuan (CV 4), Taichong (LR 3), and aduvant points, Back-shu, and the medicine
      group with oral administration of fluoxetine. After treatment of 3 months, their
      therapeutic effects were compared. RESULTS: The therapeutic effect of the catgut
      embedding group was better than that of the medication group with a very
      statistically significant difference (P < 0.005). CONCLUSION: Acupoint catgut
      embedding is a better therapy for premenstrual syndrome.

PMID- 16642614
TI  - [Study on Volt-ampere (V-A) characteristics of human acupoints].
AB  - OBJECTIVE: To study on basic Volt-ampere (V-A) characteristics of human acupoints
      and the changes with physiologic and pathologic changes, and probe their
      biophysical basis. METHODS: The research works of this research group about V-A
      characteristics of acupoints in recent 10 years were systematized and analyzed.
      RESULTS: V-A characteristic curve of human acupoints is of the both
      characteristics of non-linear and inertia. Compared with controlled point, the
      lower electric resistance characteristic of acupoints is not popular and the
      lower inertia is popular. V-A area of acupoints has no obvious circadian rhythms
      and the inertia area of a large part of acupoints has obvious circadian rhythms,
      with the phase of peak value corresponding to the phase of valley value of body
      temperature rhythms. V-A characteristics of acupoints in the patients of heart
      disease or stomach diseases changes obviously, and these changes have a certain
      specificities of acupoints. After remission of the lesion, the V-A
      characteristics of acupoints restore normal. The V-A area and the inertia area of
      acupoints in the corpse are obviously smaller than the normal person, with
      disappearance of the characteristics of both the non-linear and inertia of the
      normal person. CONCLUSION: Human acupoints have characteristics of non-linear and
      inertia, and the non-linear characteristic reflects complexity of physiology and
      behavior, while the inertia characteristic is related with energy metabolism of
      acupoints. The inertia area can more sensitively reflect human physiologic and
      pathological changes as compared with the V-A area, so it is an important index
      for the studies on electric characteristics of acupoints in the future.

PMID- 16642615
TI  - [Application of stimulation of acupoints in training of singing teaching].
AB  - OBJECTIVE: To apply the theory of channels and collaterals to the study on
      teaching of singing and to resolve problems in teaching of singing. METHODS:
      Acupoint stimulation manipulation was used for channels and collaterals
      comprehensive systematic experiment for signing, and changes of voice quality
      before and after stimulation of acupoints were investigated. RESULTS: The
      stimulation of acupoints is beneficial to discovering and developing a
      comprehensive controlling system potential for the singer, and after stimulation
      of acupoints the range of voice and the difference of the higher and lower voice
      in the subjects have significant changes. CONCLUSION: Stimulation of acupoints
      provides an experimental basis for teaching study of singing and open a new area
      of study for the theories of channels.

PMID- 16642616
TI  - [Effects of Shuanggu Yitong needling method on proliferation and differentiation
      of nerve stem cells in the Parkinson's disease model rat].
AB  - OBJECTIVE: To explore the mechanism of acupuncture in treatment of Parkinson's
      disease. METHODS: Fifty Wistar rats were randomly divided into a normal control
      group, a sham-operation control group, a model group, a Fengfu-Taichong group and
      a Shuanggu Yitong group. The hemilateral rotation Parkinson's disease model was
      prepared by micro-injection of 6-hydroxyl-dopamine into the right striatum.
      Effects of acupuncture at "Fengfu" (GV 16), "Taichong" (LR 3) hy Shoanggu Yitong
      needling method on proliferation and differentiation of nerve stem cells in the
      Parkinson's disease model rat were compared. Proliferation and numher changes of
      the nerve stem cells in the suhstantia nigra and the striatum were investigated
      with immunohistochemical method, and the number of nerve stem cells transforming
      neurons were observed with immunohistochemical double-labeling method. RESULTS:
      In the two acupuncture groups, the proliferative cells in the substantia nigra
      and thestriatum of the destroyed side increased significantly (P < 0.01), and the
      number of nerve stem cells and the number of transformed neurons in the destroyed
      side of the substantia nigra and the striatum increased significantly only in the
      Shuanggu Yitong group (P < 0.01). CONCLUSION: Shuanggu Yitong needling method can
      induce proliferation and differentiation of nerve stem cells in the substantia
      nigra and the striatum regions in the Parkinson's disease model rat.

PMID- 16642617
TI  - [Study on expression of brain aging-relative genes HSP86 and HSP84 and effects of
      acupuncture in the SAMP10 mouse].
AB  - OBJECTIVE: To probe the mechanism of acupuncture for anti-aging. METHODS: In the
      senescence accelerated mouse the SAMP10 and the SAMR1, by using RT-PCR and DIG
      labeled Northern blot technique, the expression differences of HSP84 and HSP86
      genes in whole brain, cortex and hippocampus in the 4 groups,8-month SAMR1
      control group, 8-month SAMP10 control group, 8-month SAMP10 acupuncture group and
      8-month SAMP10 non-point acupuncture group were investigated. RESULTS: In the
      SAMP10 control group, the expression of HSP84 and HSP86 were down-regulated in
      the whole brain, the cortex and the hippocampus, and they were up-regulated after
      acupuncture, tending to the normal group. CONCLUSION: Brain aging of the SAMP10
      mouse is related with abnormal expression of HSP84 and HSP86 genes, and
      acupuncture can strengthen the protection of cells, inhibit apoptosis and anti
      oxidative stress through regulating expression of HSP84 and HSP86, hence anti
      aging.

PMID- 16642618
TI  - [Point-through-point acupuncture for treatment of peripheral facial paralysis].
AB  - OBJECTIVE: To search for a more effective penetration needling method for
      peripheral facial paralysis. METHODS: The patients were divided into a treatment
      group and a control group according to visiting sequence. The treatment group of
      50 cases were treated with Yangbai (GB 14)-through-Touwei (ST 8), Yangbai (a
      little above the original point)-through-Shangxing (GV 23), Sizhukong (TE 23)
      through-Yuyao (EX-HN 4), Qianzheng-through-Yingxiang (LI 20), Dicang (ST 4)
      through-Jiache (ST 6) and Jiache-through-Yingxiang, at an angle about 45 degrees
      between the penetration needling direction and local paralysis muscle bundle, and
      the control group (n=45) with Yangbai-through-Yuyao, Zanzhu (BL 2)-through-Yuyao,
      Dicang-through-Jiache, Jiache-through-Dicang, Qianzheng-through-Dicang, Sibai (ST
      2)-through-Yingxiang. RESULTS: The cured rate and the cured and markedly
      effective rate were 76.0% and 92.0% in the treatment group, and 55.6% and 75.6%
      in the control group respectively, with significant differences between the two
      groups in the cured rate, the cured and markedly effective rate and the
      therapeutic times for cure. CONCLUSION: The penetration needling method at an
      angle about 45 degrees between the penetration needling and paralysis muscle
      bundle is more beneficial to recovery of facial paralysis.

PMID- 16642619
TI  - [Effects of scalp acupuncture on regulative ability of oxidative stress reaction
      at operation stage].
AB  - OBJECTIVE: To study on regulative action of scalp acupuncture on oxidative stress
      reaction at operation stage. METHODS: Fifty two cases selected for radical
      operation of intestinal cancer were randomly divided into a scalp acupuncture
      plus general anesthesia (scalp acupuncture group) and a simple general anesthesia
      group (general anesthesia group), 26 cases in each group. The scalp acupuncture
      group were treated first with scalp acupuncture for 20 min, followed by general
      anesthesia, with scalp acupuncture lasted till the end of operation. The general
      anesthesia group were treated only with simple intratracheal anesthesia. Effects
      of scalp acupuncture on malondialdehyde (MDA) level and superoxide dismutase
      (SOD) activity at the operation stage were observed. RESULTS: After operation,
      MDA levels decreased significantly (P < 0.05) in the two groups, but with no
      difference between the two groups in the different values of MDA before and after
      treatment (P > 0.05); there was no significant change in SOD before and after
      treatment in the scalp acupuncture group, and significantly decreased in the
      general anesthesia group (P < 0.05). There was a significant difference between
      the two groups in the different value of SOD before and after the operation (P <
      0.05). CONCLUSION: Scalp acupuncture can inhibit the decrease of SOD activity,
      reducing oxidative stress reaction at operation stage.

PMID- 16642620
TI  - [Brief introduction to professor Xue Li-gong's aponeurotic theory and long-round
      needle therapy].
AB  - Professor Xue Li-gong is engaged in clinic, scientific research and teaching of
      acupuncture and moxibustion for over 30 years, being good at treatment of
      numbness and pain of the aponeurotic system with richer learning and experiences.
      His theories about the aponeurotic system develop a school of one's own,
      including conception of the aponeurotic diseases, differentiation of the
      aponeurotic system with channels, the anatomic basis of the twelve aponeurotic
      systems, causes and pathogenesis of diseases of the aponeurotic system, and
      special treatment principles of the aponeurotic diseases, needling instruments
      for treatment, and manipulation methods. Professor XUE's long-round needle
      therapy has obvious clinical therapeutic effect on numbness and pain of the
      aponeurotic system.

PMID- 16642621
TI  - [Professor Wu Lian-zhong's experience on four needling methods at Fengchi (GB
      20)].
AB  - The paper introduces the manipulation and different clinical application examines
      of the 4 needling methods, oblique needling, horizontal needling, deep needling
      and transversal needling summarized by Prof. Wu Lian-zhong on the basis of many
      years's clinical work.

PMID- 16642622
TI  - [Late morbidity among Holocaust survivors: myth or fact?].
AB  - The harsh life in the ghettos and concentration/extermination camps during the
      Holocaust was characterized by hunger, exposure to extreme cold temperatures,
      continuous threats, infectious diseases and injuries with acute or permanent
      disabilities and extreme psychological stress. There is no definite scientific
      evidence that the Holocaust survivors are exposed to premature aging or premature
      appearance of various physical diseases. These aspects were thoroughly
      investigated in other populations: ex-prisoners of war, ex-displaced persons,
      prisoners and survivors of torture. Famine, disabilities, diseases and stress,
      particularly at the beginning of or during puberty, were found to increase
      vulnerability to later morbidity, especially hypertensive and cardiovascular
      disease and to increased mortality. This article discusses the possibility of
      premature aging among Holocaust survivors as a late effect of their life
      conditions during the Holocaust.

PMID- 16642623
TI  - [Ocular injuries related to Independence Day celebrations].
AB  - BACKGROUND: Each year, following Israel's Independence Day celebrations, patients
      are referred to the Soroka University Medical Center as a result of ocular
      injuries from items such as artificial snow spray, fireworks, plastic hammers and
      stick-lights (plastic tubes filled with fluorescent liquid). This study aims to
      describe and characterize the ocular injuries that are directly related to the
      use of these devices. PATIENTS AND METHODS: The files of all patients who were
      referred to the Department of Ophthalmology in the Soroka University Medical
      Center, between the years 1998 and 2005, during the period of Israel's
      Independence Day, were screened. If a patient sustained an injury from a device
      used during the celebration, then data relating to the age, sex, injured eye,
      diagnosis, the device that caused the injury and treatment were collected.
      RESULTS: A total of 437 patients were included in this study; fifty-two patients
      had suffered an ocular injury directly due to a celebration device. The patients'
      mean age was 17.6 years; 61.5% of the patients were male. The three most common
      ocular injuries were corneal erosions, conjuctival erosions, and superficial
      punctate keratitis (38.5%, 28.9%, and 23.0%, respectively). Other injuries
      included corneal and conjuctival foreign bodies, traumatic iritis, elevated
      intraocular pressure, and subconjuctival hemorrhage. The devices responsible for
      most of the injuries were artificial snow spray and fireworks. Ocular injuries
      from stick-light liquid, plastic hammers, and balloon explosions were seen as
      well. Almost all patients (96.1%) required medical treatment. Patients injured by
      celebration devices accounted for 27.9% of all patients seen during this period
      in our Ophthalmology Department; after several years, the rate approached 40%.
      CONCLUSION: Strict enforcement of rules and legislation regarding the use of
      celebration devices must be upheld. The public's awareness of the harm that these
      devices can cause should be strengthened.

PMID- 16642624
TI  - [Acute eosinophilic pneumonia: a potentially fatal disease under a mask of acute
      community-acquired bacterial pneumonia].
AB  - Acute eosinophilic pneumonia (AEP) is a rare and sometimes fatal disease.
      Diagnosis of AEP may be especially difficult in its early stages, before
      development of peripheral eosinophilia. This is a case study of AEP in a 27 years
      old female, reviewing etiologic factors, clinical presentation, diagnostic
      procedures and current treatment strategies. An important feature is that an
      early presentation of AEP may mimic the onset of bacterial pneumonia.
      Misdiagnosis and delay of appropriate treatment may result in development of
      respiratory failure and even death. Therefore, it is important that the relevant
      information regarding AEP presented in this article is disseminated to a wide
      forum of physicians.

PMID- 16642625
TI  - [Salmonella prosthetic knee septic arthritis successful retention of the
      prosthesis with prolonged suppressive therapy].
AB  - A 75 years old woman suffered from Salmonella enteritidis infected prosthetic
      knee joint septic arthritis. Maintenance of the prosthesis was achieved by
      surgical drainage and debridement of the joint followed by 3 weeks of intravenous
      ceftriaxone and 3 months of oral ciprofloxacin therapy.

PMID- 16642626
TI  - [Arrow injury to the elbow causing arthritis].
AB  - We describe a severe injury caused by children's games. During a children's game,
      a 13 years-old girl was injured by an arrow with a metallic head and suffered
      injury to the elbow joint necessitating surgical drainage of an inflammatory
      reaction. This article enhances other descriptions in the literature of body
      injuries caused by dangerous games, and aims to draw attention to this
      phenomenon.

PMID- 16642627
TI  - [Recording of risk factors and preventive pharmaceutical therapy among ischemic
      heart disease patients in family practice during the years 1993-1998].
AB  - The review of international literature yielded unsatisfactory performance of
      guidelines for secondary prevention of cardiovascular diseases. This study aimed
      to evaluate records of the implementation of guidelines published in 1995, for
      the treatment and follow-up of patients after myocardial infarction in family
      medicine. In a retrospective sectional cohort study we identified all the
      patients with previous myocardial infarction in the practices of 6 family
      physicians, with an overall total of 97 patients. All data was gathered from
      manual medical records. The quality of care was evaluated according to follow-up
      indicators such as performance of blood pressure measurement, LDL cholesterol
      tests and according to secondary prevention indicators such as: treatment with
      aspirin, beta blockers and statins. In the cohort of 97 patients, 20.6% had
      diabetes, 53.6% had hypertension and 88.7% performed blood pressure follow-up,
      100% cholesterol and fasting glucose tests, and 86.6% LDL cholesterol tests. Of
      the eligible patients, 98% received aspirin, 81% received beta-blockers and 76.2%
      were treated with statins. The target LDL cholesterol was not achieved by 66.7%
      of the patients. During the years 1993-1998 the quality of secondary prevention
      in the study was better than findings reported in international publications in
      corresponding years. However, the treatment of hypercholesterolemia should be
      improved.

PMID- 16642628
TI  - [Hospitalizations due to falls in the childhood population of northern Israel: a
      comparison between the years 1993-1995 and 2002-2004].
AB  - Previous studies showed that falls from height are a major cause of morbidity in
      children who live in northern Israel. These studies demonstrated major
      differences in injury severity between Arab and Jewish children, and noted that
      more children from the Arab sector were admitted to the Intensive Care Unit
      (ICU). The objective of this study was to compare the hospitalization rates at
      Rambam Medical Center in the years 1993-1995 and 2002-2004, and to evaluate
      selected demographic characteristics of these hospitalizations. We found that the
      total number of falls increased significantly during the years 2002-2004, and
      that a dramatic increase in the number of admission to ICU was notable among the
      Jewish population. These findings suggest that injury prevention programs should
      be implemented urgently on a national level.

PMID- 16642629
TI  - [Chronic fatigue syndrome].
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe fatigue and
      other non-specific symptoms. It causes disturbance of normal function.
      Uncertainty about etiology and the appropriate treatment, combined with high
      prevalence of psychiatric comorbidity, cause a problem in the perception of the
      disease by the patient, physician and society. OBJECTIVES: This review
      recapitulates the updated information regarding CFS. It addresses the following
      aspects: definitions, diagnosis, demographic figures, etiology and treatment
      options. Since much about CFS is yet to be known, a large amount of work has
      recently been performed on this subject. Current perceptions, as recognized
      today, are also presented. METHODS: A literature search was performed using
      Medline. RESULTS: Accurate diagnosis of CFS patients is low despite the disabling
      fatigue. CFS patients present certain demographic characteristics and the illness
      etiology is as yet unclear. Nonetheless, many possible directions exist with
      inconclusive evidence about certain suspected causes. There are no treatment
      guidelines available. Different treatment approaches were investigated without
      consensus on the results. CONCLUSIONS: CFS is an illness that should be taken
      seriously by the medical establishment. Conscious awareness of the malady might
      reduce rates of undiagnosed patients. The different etiologic factors showing
      some degree of involvement in CFS, might suggest that this syndrome is a multi
      factorial condition. Despite the fact that there is no distinct undisputed
      treatment, there are 2 treatments (cognitive behavioral therapy and graded
      exercise therapy) that might be effective.

PMID- 16642630
TI  - [Chronic fatigue syndrome--exercise and physical activity].
AB  - One of the major symptoms of chronic fatigue syndrome (CFS) is reduced exercise
      and functional capacity and increased fatigue symptoms following physical effort.
      A review of the literature indicates that patients that suffer from CFS are
      characterized by: low aerobic capacity, higher heart rate during sub-maximal
      exercise, higher subjective effort prescription, reduced muscle strength, and
      prolonged recovery period. Although several symptoms are a result of lack of
      physical activity, several mechanisms were suggested to explain those symptoms:
      pathological heart rate control, reduced aerobic metabolic capacity, reduced
      blood supply to the working muscles and nerve system dysfunction. Participating
      in guided exercise programs was found to be the most effective treatment in
      improving exercise and functional capacity, reducing fatigue syndromes and
      improving patients' daily function.

PMID- 16642631
TI  - [The male's role in the etiology of preeclampsia].
AB  - Preeclampsia is a major cause of morbidity and mortality in mothers, fetuses, and
      neonates worldwide, with 5%-10% of human births being affected. The cause is
      still uncertain, and many controversies exist concerning its management.
      Preeclampsia-eclampsia is due to the failure of extra-villous cytotrophoblast to
      invade the maternal uterine spiral arteries to a sufficient depth, inducing poor
      vascular exchanges between the mother and the placenta. This physiological
      endovascular trophoblast invasion represents a remarkable immunological placental
      maternal interaction. Recent data strongly indicate an important role for the
      male partner in the causation of this common pregnancy disorder. This review aims
      to discuss the relevant literature and to explain how paternal, relational and
      sexual factors play an important role in the etiology of preeclampsia.

PMID- 16642632
TI  - [Depression in children and adolescents].
AB  - Early onset depression is a widely prevalent, recurrent and familial disorder
      with a tendency to continue throughout adulthood. It is often accompanied by
      other comorbidities such as substance abuse, bipolar disorder, suicidal behavior
      and significant impairment in the child's psychosocial development. The risk
      factors include genetic, psychological and environmental factors and gene
      environment interaction. The evidence-based therapies include cognitive, inter
      personal and pharmacological interventions. Recently, the FDA published a warning
      concerning the use of these pharmacological agents in the pediatric age group.
      Further research is needed to assess the efficacy and safety of these
      interventions and to better understand the etiological factors.

PMID- 16642633
TI  - [Tourette syndrome: from a neurological clinic to a multidisciplinary approach].
AB  - Tourette Syndrome (TS) is a chronic, familial disorder, characterized by
      involuntary motor and phonic tics that wax and wane in severity. TS is frequently
      accompanied by behavioral, emotional and cognitive problems that are often more
      incapacitating than the tic disorder itself. After a review of the disorder, in
      which the multidisciplinary aspects are emphasized, the article describes the
      clinical features of 60 children with TS, 49 boys and 11 girls, aged 13 +/- 3.6
      years (mean SD), treated in the Neuropediatric Unit at Shaare Zedek Medical
      Center. The children described had both motor and vocal tics, but also had ADHD
      (n = 44), obsessive-compulsive disorder (n = 32), learning disabilities (with 12
      children learning in special education frameworks) and behavioral disorders (n =
      36). The clinical profile of this group of children with TS is similar to that
      reported on referred patients regardless of cultural background. Since children
      with TS manifest multiple comorbidities, optimal therapy mandates the cooperation
      of a multidisciplinary team including a pediatric neurologist, a child
      psychiatrist, a psychologist and a family therapist. Working in concert, these
      specialists can implement a multimodal approach, addressing the neurological and
      psychiatric aspects of TS as well as enhancing the child's coping skills with the
      disorder itself and its consequences.

PMID- 16642634
TI  - [Autoimmune mechanisms in paraneoplastic neurological diseases: the paradigm of
      opsoclonus myoclonus ataxia syndrome].
AB  - Paraneoplastic Neurologic Diseases (PND) are remote complications of certain
      neoplastic diseases characterized by distinct neurological deficits in the
      central as well as the peripheral nervous system. The neurological disorders are
      usually clinically evident before the cancer is identified. PND are rare
      syndromes believed to have an immunological link where antibodies or activated T
      cells are acting against self antigens shared by the tumor cells and neurons.
      Most of these onconeural antigens are located in the cytoplasm-nuclear
      compartment of the cell, whereas others are located at the membrane and act as
      receptors or ion channels. This short review discusses the autoimmune mechanisms
      involved in PND in general and in opsoclonus-myoclonus-ataxia in particular. The
      article attempts to clarify why in most PND the immune effector mechanisms
      against onconeural antigens detected in sera of patients may not be the direct
      cause of the neurological deficit. We elaborate on the difference between the
      immune response against cytoplasmic-nuclear antigens as opposed to membranal
      antigens with regard to the fact that: a) the nervous system is considered immune
      privileged; b) neither the tumors nor the neurons have an optimal expression of
      MHC class I antigens and onconeural epitopes on the membrane. The availability of
      onconeural antigens to the immune effectors mechanisms is probably the main
      reason why there are few animal models for PND.

PMID- 16642635
TI  - [Physicians who experimented on themselves: risk-taking among physicians and
      researchers].
AB  - Throughout history, we can find physicians and scientists who made important
      discoveries through self-experimentation or by risk-taking. Some were consciously
      exposed to plagues, some swallowed germs or chemicals and some put themselves in
      extreme physiological situations. Today, it seems that these stories are
      completely unnecessary: ethics, together with concrete controlled studies
      guidelines, suffice to avoid self-experimentations.

PMID- 16642636
TI  - [Utilizing medical presentations in medical education].

PMID- 16642637
TI  - Pediatric liver transplant recipients: mortality analysis over 20 years.
AB  - Orthotropic liver transplantation (OLT) has become standard and accepted care for
      pediatric patients with end-stage liver disease. Two large pediatric OLT series
      are analyzed to determine excess death rates (EDR) over 20 years. The EDR
      decreases over time and is lower with more recent transplant recipients who have
      benefited from improved tacrolimus-based immunosuppression and transplant
      techniques. Fifteen- to 20-year EDR is 5 deaths/1000. Biliary atresia is the most
      common pediatric indication, and these recipients do better than those with other
      types of liver disease. Most deaths occur in the first post-transplant year, with
      infection being the largest cause.

PMID- 16642638
TI  - Notes regarding confidence intervals and statistics for standardized mortality
      ratios and survival curves in the insurance industry.
AB  - Methods have been described for evaluating the statistical validity of insurance
      experience studies and the translation of medical literature studies to life
      insurance ratings. These have not seen widespread adoption in the insurance
      literature. This article is intended to encourage the use of these existing
      methods and describe other methods in the biostatistical literature.

PMID- 16642639
TI  - Mortality in a complete 4-year follow up of 85-year-old residents of Leiden,
      classified by serum level of thyrotropin and thyroxine.
AB  - BACKGROUND: The authors of the source article emphasize the clinical tendency to
      screen for, detect and treat for thyroid dysfunction in very elderly patients, in
      which it is a fairly common disorder, often with occult or no symptoms. Published
      evidence is conflicting on the benefit, if any, of such a program. Accordingly,
      they devised a prospective, population-based study to determine outcomes,
      including survival outcome, based on serum levels of thyroid-stimulating hormone
      (TSH) and thyroxine. METHODS: A cohort of 558 subjects who had their 85th
      birthday between September 1997 and September 1999 was enrolled after consent of
      the subject and screening examination that included serum TSH and thyroxine
      levels. This represented a 79% sample of all 85-year-old residents of Leiden, the
      Netherlands. Follow up was complete for survival 4 years to the subject's 89th
      birthday or prior death, although 70 subjects refused the annual re-examination.
      Thyroid function, disability, cognitive function and number of chronic diseases
      were analyzed, in addition to mortality, through Cox regression and other
      statistical methods. RESULTS: In 67 subjects with abnormally high TSH (>4.8 mIU/
      L), the mean annual mortality rate was derived as 64 deaths per 1000 per year. In
      the 491 subjects with normal TSH or low TSH (<0.3 mIU/L), the mean annual
      mortality rate was derived at 114 per 1000 per year. Laboratory evidence of
      hypothyroidism (initially low serum thyroxine) was found in only 37 of the 67
      subjects. CONCLUSION: In the 13% of elderly subjects in Leiden with abnormally
      high serum TSH levels, the mean annual mortality rate was significantly lower
      than the mortality rate in the 87% of the elderly patients with normal or low
      serum TSH. The significance is based on 95% confidence levels of the Poisson
      distribution. The rate in the group with high TSH levels had 16 deaths in 264
      person-years of follow up (FU). The majority with normal or low TSH levels had
      193 deaths in 1698 person-years of FU.

PMID- 16642640
TI  - Diabetes update.
AB  - The purpose of this article is to provide a general update of diabetes with a
      focus on newer developments that may impact risk assessment. The main reasons for
      concern about diabetes are the associated microvascular and macrovascular
      complications. Control of blood glucose levels, primarily assessed by measurement
      of hemoglobin A1c, has been shown to reduce the occurrence of microvascular
      complications. In conjunction with control of other risk factors, control of
      blood glucose levels reduces the occurrence of macrovascular complications. Type
      1 diabetes is now known to be an autoimmune disease. For unknown reasons, the
      patient's immune system destroys its own pancreatic insulin-producing beta cells.
      The hallmark of type 2 diabetes is insulin resistance, which may be mediated by
      one of a number of gene defects. At some point, the pancreatic beta cells are
      unable to compensate for the insulin resistance by increasing insulin secretion.
      Type 2 diabetes then appears. Prediabetes, encompassing impaired fasting glucose
      and impaired glucose tolerance, is an important clinical entity that precedes the
      diagnosis of diabetes in many cases. Diet and exercise are the most important
      interventions for reducing the progression of insulin resistance to diabetes.
      Once diabetes develops, medications are matched to pathophysiology.

PMID- 16642641
TI  - Cost/benefit of laboratory tests.
AB  - BACKGROUND: Insurers choose laboratory test requirements to maximize the
      relationship between cost and benefit. Traditional means of analysis, such as
      experience studies, take years or decades to perform. Cost/benefit models provide
      a more timely option by projecting possible experience according to different
      scenarios. METHODS: The article describes how to create a cost/benefit model.
      RESULTS: Hemoglobin A1c and hepatitis C virus antibody tests--and more generally
      tests reflexed after a prior abnormal test--often have the highest cost/benefit
      ratio. Mortality savings is higher for tests done on older aged applicants
      (except for impairments that are more common in young people) and on tobacco
      users. Indirect costs, such as time, overhead, delays, and false positives,
      decrease the cost/benefit of testing. Entire markets may follow inefficient
      testing strategies because insurers do not deviate from the practices of market
      leaders. CONCLUSION: Cost/benefit analysis helps insurers set underwriting
      requirements by age, gender, tobacco/nontobacco status, and policy amount.

PMID- 16642642
TI  - Cardiovascular risk factors, BMI and mortality in a cohort of Swiss males (1976
      2001) with high-sum-assured life insurance cover.
AB  - BACKGROUND: This long-term study investigates the influence of body mass index,
      blood pressure, smoking habits, impaired glucose metabolism and history of any
      disease on the mortality of Swiss males holding life insurance cover with high
      sums assured. METHODS: In a prospective study (1976-2001) including 22,927 Swiss
      insured males holding life insurance cover with high sums assured, the prevalence
      of overweight and obesity was compared with data from the general population. The
      relationship between BMI and all-cause mortality was assessed using a Cox
      proportional hazard model adjusted for age and calendar year, thereby controlling
      for mortality improvement over time. Multivariable models were used to
      investigate the impact of multiple cardiovascular risk factors on all-cause and
      cardiovascular mortality. The evolution of hazard ratios was assessed by dividing
      the observation period into two periods (1976-1985 vs 1986-2001). RESULTS: The
      prevalence of overweight was 35.7% and of obesity 6.2%. The prevalence of both
      increased over time. The association between BMI and all-cause mortality showed a
      'U'-shaped curve with the nadir at 22.0-23.9 kg/m2. Compared with this optimal
      range, a relative risk of 1.76 (CI 95%: 1.17-2.67) was found for a BMI in the
      range of 30.0-31.9 kg/m2, representing the lowest category of obese subjects. In
      the multivariable model, obese subjects had a hazard ratio of 1.76 (CI 95%: 1.34
      2.30) compared against those with normal BMI. The hazard ratios for all-cause
      mortality associated with prehypertension, stage 1 and stage 2 hypertension were
      1.58, 2.28 and 3.14, respectively, all of them being statistically significant.
      The results for cardiovascular mortality were more pronounced, however, with
      wider confidence intervals. Comparing the two observational periods, the hazard
      ratios for obese vs non-obese subjects were 1.57 (CI 95%: 1.08 to 2.28) in period
      1 and 2.41 (CI 95%: 1.71-3.39) in period 2. Similarly, the hazard ratio for
      combined stages 1 and 2 hypertension vs the other categories of JNC7 were 1.52
      (CI 95%: 1.15-2.01) and 1.96 (CI 95%: 1.49-2.58) for periods 1 and 2,
      respectively. CONCLUSIONS: In this cohort of Swiss insured males holding life
      insurance cover with high sums assured, prevalence trends of elevated BMI are
      similar to those in the general population. The relative mortality risks
      associated with cardiovascular risk factors are higher than in the general
      population and, in the case of elevated BMI and high blood pressure, might
      exhibit an increase over time.

PMID- 16642643
TI  - The bird flu and insurance medicine.

PMID- 16642644
TI  - Pulmonary function tests.

PMID- 16642645
TI  - Positive computer-generated exercise electrocardiogram.
AB  - The use of computerized averaging of the electrocardiogram (ECG) during stress
      testing has facilitated the removal of motion artifacts and baseline shifts.
      However, this process can introduce errors, which may not be appreciated by
      medical directors. Such errors can lead to significant ST depression in the
      absence of coronary artery disease. Such false-positive tests may lead to anxiety
      in the applicant, delays in accepting the application and unnecessary additional
      testing. This case study illustrates a common pitfall associated with using only
      a computer-generated exercise ECG for risk assessment of a life insurance
      applicant.

PMID- 16642646
TI  - Neurofibromatosis.
AB  - Neurofibromatosis is a heritable disease characterized by disordered growth of
      ectodermal tissues.

PMID- 16642647
TI  - Bicuspid aortic valve.
AB  - Bicuspid aortic valve is the most common congenital cardiac malformation and may
      be responsible for more mortality and morbidity than the combined effects of all
      the other congenital heart defects.

PMID- 16642648
TI  - The legacy of Dr William Heberden.

PMID- 16642649
TI  - Depression: A major public health problem facing the Caribbean.

PMID- 16642650
TI  - Dietary intake of choline and plasma choline concentrations in pregnant women in
      Jamaica.
AB  - Choline is an essential nutrient for humans and its availability during pregnancy
      is important for optimal fetal development. The Food and Nutrition Board of the
      Institute of Medicine in the United States of America has set the adequate
      choline intake during pregnancy at 450 mg/day. There is limited data available on
      normal plasma choline concentrations in pregnancy. Moreover, there are neither
      documented studies of choline intake among pregnant women in the Jamaican
      population nor of free plasma choline concentrations during pregnancy. Sixteen
      women presenting to the antenatal clinic of the University Hospital of the West
      Indies (UHWI) at 10-15 weeks of gestation were selected for this pilot study. A
      food frequency questionnaire was administered to estimate frequency of
      consumption of foods rich in choline. Fasting blood samples were collected by
      venepuncture and plasma assayed for choline using liquid chromatography
      electrospray ionization isotopic dilution mass spectrometry. Most of the women
      reported consumption of diets that delivered less than the recommended choline
      intake (mean +/- SEM, 278.5 +/- 28.9 mg). Mean plasma choline concentration was
      8.4 +/- 0.4 micromol/L. This falls below the normal concentration (10 micromol/L)
      reported for individuals that are not pregnant and pregnant (14.5 micromol/L).
      The results of this study may be an indication that the choline included in the
      diet of pregnant women in Jamaica may not be adequate to meet both the needs of
      the mother and fetus and that further studies are warranted to determine clinical
      implications.

PMID- 16642651
TI  - Clinical and epidemiological characteristics of adult and adolescent patients
      newly diagnosed with the human immunodeficiency virus at a Jamaican clinic for
      sexually transmitted infections.
AB  - Persons infected with the human immunodeficiency virus (HIV) may have protean
      clinical manifestations. These characteristics have not been described for adult
      patients in Jamaica. This study was conducted to determine the clinical and
      epidemiological characteristics of adult and adolescent persons newly diagnosed
      with HIV presenting at a specialized clinic for sexually transmitted infections
      (STI). A retrospective analysis of the medical records of adult and adolescent
      patients newly diagnosed with HIV was undertaken over a 12-month period. The
      results showed that most patients (64%) were between 20 and 39 years old (age
      range 14-68 years, M:F ratio 1.4:1). Heterosexual practice was admitted to by 77%
      of patients. At the time of presentation most patients (53%) were asymptomatic
      while 24% had some symptoms and 21% had acquired immunodeficiency syndrome
      (AIDS). The most common presentation was generalized lymphadenopathy (67%) which
      was significantly higher than skin rash (27%), oral candidiasis (24%), cough
      (24%), weight loss (24%) and pallor of mucous membranes (19%, p < 0.001). This
      study affirms that young people account for the majority of new cases of HIV
      infection. The heterosexual route was the predominant mode of transmission.
      Generalized lymphadenopathy was the commonest presenting feature of persons newly
      diagnosed with HIV infection.

PMID- 16642652
TI  - Clinicopathologic profile of gastric carcinomas at the University Hospital of the
      West Indies.
AB  - The objective of this study was to examine the clinicopathologic features of
      gastric cancer seen at the University Hospital of the West Indies (UHWI) and to
      compare the findings with other studies. A retrospective study was conducted
      using data obtained from the surgical pathology reports of all gastrectomies and
      gastric biopsies during the period January 1993 and December 2002. Additional
      cases were identified from the Department of Surgery's audit database.
      Demographic, clinical and pathological features were analyzed. Two hundred and
      sixteen patients were identified, 126 males and 90 females. One hundred and
      thirty-six underwent biopsy procedures but no definitive surgery aimed at cancer
      eradication, while 70 had gastrectomy. The peak age prevalence in both males and
      females was the 70-79-year age group. While the antrum was the commonest site,
      there was an overall increase in tumours of the gastro-oesophageal junction and
      tumours of the entire stomach in the latter five-year period of the review
      especially in the 50-59-year age group. Epigastric pain and constitutional
      symptoms were the common presenting features, and the most common gross tumour
      characteristic was an ulcerating mass, while histologically, the intestinal
      variety was most common. Lymph node metastases were common. Helicobacter pylori
      (Hpylori) were present in 16.7% while chronic multifocal atrophic gastritis was
      present in 40%. This study indicates that the gastric cancer pattern is typical
      of developing countries. However, the low prevalence of H pylori in the resected
      specimens may indicate the importance of other risk factors for gastric cancer
      development in this population. This warrants further study.

PMID- 16642653
TI  - Depression and its associated factors among patients attending chronic disease
      clinics in southwest Trinidad.
AB  - This study determined the prevalence of depression and associated factors, among
      patients attending chronic disease clinics in Southwest Trinidad. This was a
      cross-sectional survey using a sample of consecutive patients at four large
      clinics. To determine the presence of depression, an interviewer-applied modified
      Zung Scale was validated The modified Zung scale, at the cut-off index of 60, has
      a sensitivity of 60% and a specificity of 94%. Seven hundred and thirty-four
      completed questionnaires were received, a response rate of 76%. The patients were
      primarily Indo-Trinidadian (70%), over 50 years (76.4%) and female (72.3%). The
      prevalence of depression was 28.3%. There were statistically significant
      differences in the level of depression by age, gender, educational level achieved
      and occupation (p < 0.05). There were also statistically significant differences
      in the level of depression by the number of presenting complaints, the number of
      chronic diseases, the presence of arthritis, the presence of diabetes mellitus
      with another chronic disease and the presence of ischaemic heart disease (p <
      0.05). No significant differences were found with respect to ethnicity (p = 0.97)
      or the presence of diabetes mellitus by itself (p = 0.34). Results of logistic
      regression indicate that the independent predictors of depression (p < 0.05) were
      the level of education achieved, those with higher levels of education had less
      depression; the number of presenting complaints, those with more presenting
      complaints were more likely to be depressed and the presence of arthritis and
      female gender. It is imperative that policy be developed to address the mental
      health problems of patients attending these chronic disease clinics.

PMID- 16642654
TI  - Seroprevalence of Legionella pneumophila in pneumonia patients in four major
      hospitals in Trinidad and Tobago.
AB  - Trinidad and Tobago is an island-state in the Caribbean with a size of 5,128
      square kilometers and a population of 1.3 million. Pneumonia is a leading cause
      of death in Trinidad. This project determined the frequency of Legionella
      pneumophila in patients with pneumonia, investigated the relationship between
      pneumonia and selected risk factors. Serum and demographic data were collected
      from 123 patients, diagnosed with pneumonia. Sera were tested for L pneumophila
      Ig G/M/A and IgM. All analyses were done using the SPSS statistical package. Of a
      total of 123 serum samples tested, 39 (31.7) were positive for L pneumophila
      IgM/G/A while 2 (1.6%) were positive for IgM only. Hospitals, gender and
      ethnicity did not significantly (p > 0.05; chi-squared) affect the seroprevalence
      of L pneumophila. Overall, the prevalence of L pneumophila assayed was not
      significantly (p > 0.05, chi-squared) affected by co-morbidities.

PMID- 16642655
TI  - Thal-Hatafuku oesophagogastroplasty: an effective option in the palliation of non
      chagasic megaesophagus.
AB  - The palliation of patients with megaesophagus secondary to achalasia of the
      cardia presents significant challenges to the surgeon. Experience with palliation
      of megaesophagus secondary to Chagas' disease suggests that options other than
      cardiomyotomy or oesophagectomy can result in satisfactory outcomes. A small
      series of patients with non-chagasic megaesophagus who were treated with a
      gastroesophagoplasty procedure is discussed.

PMID- 16642656
TI  - Penetrating type intraosseous ganglion cyst of the lunate bone.
AB  - Intraosseous ganglion cysts of the carpal bones located in the lunate are one of
      the rarely seen pathologic conditions. Here we present a case of the penetrating
      type of intraosseous ganglion cyst located in the lunate as an uncommon cause of
      wrist pain. The patient was successfully treated by surgical intervention.
      Intraosseous ganglion cyst should be considered in the differential diagnosis of
      chronic dull wrist pain.

PMID- 16642657
TI  - Depression in adolescence: new developments.
AB  - Depression in adolescence is under-recognized although its associated burden of
      illness is very high. Some frequent associations with depression in this age
      group are under-achievement, poor lifestyle choices including substance abuse,
      and a high risk of the persistence of the illness into adulthood There is also an
      increased risk of mortality related to suicide and harmful lifestyles. For
      depression in adolescents to be reduced, there needs to be strong collaboration
      among health professions, adolescents and their caregivers. Non-mental health
      clinicians must expand their role and become better prepared to recognize,
      prevent and treat depression in this age-group. Greater public awareness must
      also be achieved so that adolescents and their caregivers can seek help early.

PMID- 16642658
TI  - Image and diagnosis. Intracranial haemorrhage due to vitamin K deficiency, as the
      first symptom of extrahepatic biliary atresia.

PMID- 16642659
TI  - A six-year study of hydroxyapatite-coated root-form dental implants.
AB  - BACKGROUND: The effect of hydroxyapatite coating of dental implants is
      controversial. The long-term fate of hydroxyapatite-coated implants has been the
      subject of some criticism. PURPOSE: The aim of this retrospective study was to
      assess the clinical outcome of hydroxyapatite-coated cylindrical root-form
      endosseous Impladent dental implants (LASAK Ltd, Prague, Czech Republic) during a
      six-year course. METHODS: Three-hundred and ninety-one consecutively placed
      implants were used in 169 patients and followed for four to six years. Interval
      and cumulative success of implants and prostheses survival was tabulated.
      Marginal bone loss was measured RESULTS: Of the total number of implants, 98.5%
      achieved initial osseointegration. The cumulative success was 98.3% after one
      year, 97.0% after three years, 92.8% after five years and 90.4% after six years.
      The prostheses survival at the end of the study was 100% for fixed bridges
      totally supported by implants, 96.5% for fixed bridges with combined implant and
      tooth support, 94.2% for single crowns, 90.9% for mandibular overdentures and
      81.3% for maxillary overdentures. Marginal bone loss averaged 2.4 +/- 0.8 mm at
      the end of five years. CONCLUSION: The success rate of the investigated
      hydroxyapatite-coated implants was comparable with the data presented in the
      literature and with the results of the similar implants without hydroxyapatite
      coating. However, the marginal bone loss was of interest. Longer monitoring of
      the implants is necessary.

PMID- 16642660
TI  - The use of oxidized regenerated cellulose (surgicel) in closing Schneiderian
      membrane tears during the sinus lift procedure.
AB  - During the sinus lift procedure, undesirable perforations of the Schneiderian
      membrane can occur in up to 58% of cases. Several methods for their closing
      exist. This article presents a method of covering the perforation with a strip of
      oxidized regenerated cellulose (Surgicel). One or two layers of material swell
      after being saturated with blood, turning into a gelatinous mass and forming a
      tight and mechanically resistant seal. This simple method has been successfully
      tested on 223 perforations of the Schneiderian membrane that occurred over a
      period of 58 months.

PMID- 16642661
TI  - Trichophyton mentagrophytes var. quinckeanum as a cause of zoophilic
      dermatomycosis in a human family.
AB  - Trichophyton mentagrophytes var. quinckeanum is a zoophilic form of T.
      mentagrophytes. It induces murine favus in the form of coarse yellow scutules
      bigger than 1 cm in diameter. In March, 2002, a 52-year-old male patient was
      examined at the Dermatology Clinic of the Medical Faculty in Kosice with a 1-week
      anamnesis of a solitary, oval, annular focus, 3 cm in diameter, on the right side
      of his face, located subauricularly. When providing the history, he has mentioned
      that his 12-year-old son has a ,,similar skin disease". Clinical examination of
      the son showed similar annular oval lesion, size about 2 x 3 cm, located in the
      right chest region. Since January 2002 the family has kept a guinea pig. They
      have obtained it through a mediator from the Kosice ZOO. The material for
      mycological examination was taken from peripheral parts of the foci or
      desquamating lesions from the father, son, and the guinea pig. Scales were
      examined microscopically in 20 % KOH solution with Parker's blue-black ink. The
      findings proved the presence of septal hyphae and formation of arthrospores.
      Thus, dermatomycosis was confirmed in the father and son, caused by T.
      mentagrophytes var. quinckeanum, the source of which was a pet guinea pig (Fig.
      3, Ref. 17).

PMID- 16642662
TI  - Behcet's syndrome.
AB  - Behcet's syndrome is a systemic illness of unknown etiology characterized by
      necrotising vasculitis originally described in Turkey. Typical manifestations
      include urogenital ulcerations, eye inflammation and migratory thrombophlebitis.
      An unusual course of this disease is described. A 56 year-old man was admitted to
      the hospital with fever, milk-glass opacities on chest x-ray, mucosal defects on
      the tongue and penis, hematuria and proteinuria with functional disorder of
      kidney. Chlamydia pneumoniae, CIK positivity and C 3 complement decrease were
      found. Antibiotics and antimycotic drugs have shown only slight improvement of
      pulmonary lesions. An excellent effect in all pathological findings was achieved
      after prednison administered in dosis of 1 mg/kg and later cyclophosphamide
      administration (Fig. 7, Ref. 12).

PMID- 16642663
TI  - Serum C-reactive protein (CRP) in association with various nutritional parameters
      in maintenance hemodialysis patients.
AB  - Malnutrition and inflammation are common in hemodialysis (HD) patients, and are
      usually closely associated. Serum C-reactive protein (CRP) concentrations have
      been found to be significantly elevated in hemodialysis patients and reflects
      chronic inflammation, and as an acute-phase reactant, is a sensitive and
      independent marker of malnutrition. To investigate the association of serum CRP
      level with some nutritional variables in diabetic and non diabetic end-stage
      renal failure patients undergoing regular hemodialysis, we designed a study on 36
      maintenance hemodialysis patients (f = 15, m = 21), consisting of 25 non-diabetic
      HD patients and 11 diabetic HD patients. In this study a near significant
      difference of CRP between diabetic and non-diabetics of all patients with more
      values of CRP in diabetics and a significant difference of CRP between diabetic
      and non-diabetics of female HD patients with more values in diabetics were seen.
      A significant difference of CRP between males and females of non-diabetic
      population with more values of CRP in males was found too. An inverse correlation
      of serum CRP with serum cholesterol and triglyceride levels and a near
      significant positive correlations of CRP with serum ALP and with serum intact
      parathormone (iPTH) were found too. An inverse correlation of serum CRP with
      dialysis efficacy was also seen. No significant association between serum CRP and
      serum albumin was seen. Compatible with some studies and in contrast to some
      other studies, the association of serum albumin with serum CRP levels in this
      study was insignificant. The positive correlation of high serum iPTH with
      inflammation implies further need to control hyperphosphatemia and secondary
      hyperparathyroidism in HD patients, also inverse correlation of serum CRP with
      cholesterol and triglyceride further support the malnutrition-inflammation
      complex syndrome (MICS) which frequently seen in hemodialysis patients (Tab. 3,
      Fig. 3, Ref. 42).

PMID- 16642664
TI  - Combination of osteotomy of the first metatarsal according to Frejka with McBride
      operation procedure in surgical therapy of extreme hallux valgus.
AB  - Hallux valgus is to be perceived as a complex of deformities of the first ray of
      the foot, often accompanied by deformity of forefoot. Although, this deformity
      can be treated with as many as 200 surgical procedures, the authors would like to
      demonstrate the effect of their own approach. The authors evaluate the results of
      hallux valgus surgery combining the operation according to McBride and wedge
      osteotomy of the first metatarsal (MT) basis in 21 patients (37 surgeries) with
      post-surgical follow-up lasting from 29 to 45 months (i.e. 3 years in average).
      Pre-operative mean intermetatarsal 1-2 angle revealed by radiographs was
      surgically corrected from 21.7 degrees at the baseline to the mean degree of 8.8.
      The pre-surgical average 45.9-degree of great toe valgosity proved by radiographs
      was surgically improved to the mean of 13.5 degrees. 87% of patients expressed
      their personal satisfaction with their surgical results. The authors consider the
      combination of wedge osteotomy of the first metatarsal basis with the operation
      according to McBride to be suitable in the therapy of extreme valgosity of great
      toes with increased metatarsal angle between first and 2nd metatarsal in young
      patients with minimum of changes in the metatarsophalangeal joint developed due
      to arthrosis (Tab. 2, Fig. 6, Ref. 7).

PMID- 16642665
TI  - Complications in patients with uveal melanoma after stereotactic radiosurgery and
      brachytherapy.
AB  - Malignant uveal melanoma is the most common intraocular tumour with the incidence
      about 0.7-1.0 in 100.000 inhabitants. Enucleation is still a standard treatment
      method for posterior uveal melanoma, but conservative methods are an adequate
      alternative. Brachytherapy has been used more than 20 years in our Department,
      stereotactic radiosurgery was introduced in 1999. In years 1991-2004, 145
      patients with uveal melanoma were treated at the Department of Ophthalmology,
      Comenius University, Bratislava. Conservative treatment/brachytherapy is
      indicated in tumours staged T1-T3. Survival is comparable for all conservative
      methods. After stereotactic radiosurgery (Linac), the necessity of enucleation
      because of complications (e.g. secondary glaucoma), after brachytherapy (Ru106
      plaques), it was 5%. Conservative methods and combined techniques are effective
      methods for the therapy of uveal melanomas (Fig. 5, Tab. 1, Ref. 6).

PMID- 16642666
TI  - Dual inhibition of angiotensin converting enzyme and neutral endopeptidase
      produces effective blood pressure control in spontaneously hypertensive rats.
AB  - BACKGROUND: The synergistic effects of the combined ACE and NEP inhibition is
      based both on the blockade of angiotensin II synthesis and degradation of
      vasoactive peptides and NEP substrates (ANP, arginine, endothelial cells,
      guanylat cyclase etc.), including bradykinine and the natriuretic peptides, which
      contribute to vasodilatation, diuresis and improvement of myocardial function.
      OBJECTIVES: This study was undertaken to asses the hypotensive effect of a dual
      ACE/NEP inhibitor (omapatrilat) in comparison to a NEP inhibitor (candoxatril)
      and ACE inhibitor (enalapril) in SHRS. METHODS: The study was performed in 130
      male spontaneously hypertensive rats (SHRS) that were divided into 4 groups and
      treated orally by a gastric tube for 14 days according to the following dosage
      regimen: omapatrilat (40 mg/kg b.w./24 h); candoxatril (30 mg/kg b.w./24 h);
      enalapril (20 mg/kg b.w./ 24 h) and control (water). Systolic blood pressure
      values were determined at the beginning of the study by the tail-cuff
      pletysmographic method, at the 7th and 14th day of the treatment, as well as 14
      days after the end of the drug administration. For evaluation of the effect of
      omapatrilat, candoxatril and enalapril on the investigated parameters (plasma
      atrial natriuretic peptide and serum ACE), 10 animals from the control group were
      sacrificed at the beginning of the study, and afterwards 10 animals from each
      group were also sacrificed on the 7th and 14th day of the treatment, as well as
      14 days after the end of the drug administration (28th day). RESULTS: The dual
      ACE/NEP inhibitor, omapatrilat and the ACE inhibitor, enalapril lowered SBP more
      effectively than the NEP inhibitor, candoxatril at all time points of the
      experiment (p < 0.01). Omapatrilat was slightly more effective than the enalapril
      treatment. CONCLUSIONS: Two-week treatment with the dual ACE/NEP inhibitor
      omapatrilat caused a significant decrease of the SBP, inhibition of the serum ACE
      activity and increase of the plasma ANP values, and therefore it should be
      considered as a new potential therapeutic agent in blood pressure management
      (Tab. 3, Fig. 2, Ref. 20).

PMID- 16642667
TI  - Surfactant lung lavage using asymmetric high-frequency jet ventilation followed
      by conventional ventilation in rabbits with meconium aspiration.
AB  - BACKGROUND: Severe impairment of lung functions in meconium aspiration syndrome
      (MAS) often needs the application of combined therapeutic approach. In our recent
      study, surfactant lung lavage during asymmetric high-frequency jet ventilation
      (HFJV) removed more meconium than surfactant lavage during conventional
      ventilation, however, after the lavage excessive CO2 elimination was observed
      during HFJV. OBJECTIVES: We hypothesized that the combination of asymmetric HFJV
      during surfactant lung lavage and conventional ventilation in the post-lavage
      period may be of benefit in a rabbit model of MAS. METHODS: Suspension of human
      meconium in saline (25 mg/ml, 4 ml/kg) was instilled into the tracheal tube of
      conventionally ventilated (frequency, f, 30/min, inspiration time, Ti, 50%)
      anesthetized rabbits to cause a respiratory failure. Animals were then lavaged
      (10 ml/kg in 3 portions) with diluted surfactant (Curosurf, 100 mg of
      phospholipids/ml) or saline during asymmetric HFJV (f, 300/min, Ti, 70%). After
      the lavage, animals were ventilated conventionally (f, 30/min, Ti, 50%) for next
      1 hour. RESULTS: Surfactant lung lavage during asymmetric HFJV removed more
      meconium pigments and solids than saline with HFJV (p < 0.05 or p < 0.01,
      respectively). Moreover, application of asymmetric HFJV facilitated the lavage
      fluid removal in both groups. In the post-lavage period, improved oxygenation,
      lung compliance, right-to-left pulmonary shunts, and reduced ventilatory
      requirements were found in the surfactant group (p < 0.05), while pCO2 was kept
      in the normal range. CONCLUSIONS: Surfactant lung lavage by asymmetric HFJV
      followed by conventional ventilation is advantageous combination in rabbits with
      MAS and may be tested in neonatal MAS (Tab. 2, Fig. 2, Ref. 12).

PMID- 16642668
TI  - Combination therapy of colorectal carcinoma.
AB  - The aim of the study was to optimise the present therapy for colorectal carcinoma
      according to the standard therapeutic protocol. At the Ist Department of Surgery
      of the LF MU St. Anna Hospital in Brno and at the Department of Radiation
      Oncology of the same hospital, 262 patients with colorectal carcinoma were
      treated in period 2000-2002. Neoadjuvant radiotherapy concomitant with
      chemotherapy was applied for 5-6 weeks. After this procedure, a 5-6-week break,
      the restaging and the surgical intervention have followed. A radical surgical
      operation was carried out in 74.1% cases. The survival of stage IV patients was
      worse compared to other stages, and the presence of organ metastases markedly
      impaired the prognosis. We have shown in our study, that radical surgery is still
      the best therapeutic method for colorectal tumors. Within the surgical technique,
      the use of a harmonic scalpel has proved beneficial, as it enables a bloodless
      operative field while ensuring the necessary radicality and preserving the nerve
      plexuses. Neoadjuvant chemo-radiotherapy is considered a method of choice in
      rectal tumors surgery; it shows better results than radiotherapy only. Its
      inclusion into standard protocols has been still hindered by the lacking evidence
      of effectiveness at the II or I level. The possibility of administering oral
      fluoropyrimidines makes these studies even more attractive (Fig. 6, Ref. 30).

PMID- 16642669
TI  - 20-year experience with operations for popliteal artery aneurysm.
AB  - At the 2nd Department of Surgery, St. Anne's University hospital Brno, a total of
      76 operations for popliteal artery aneurysm were performed in 67 patients in the
      last 20 years, in period 1985-2004. 63 operations were elective and 13 urgent.
      For reconstruction, autologous saphenous vein was used in 53 cases, vascular
      prosthesis in 15 cases, and a cryopreserved vein allograft in 3 cases. In 5
      cases, amputation for advanced lower limb ischaemia was performed without
      arterial reconstruction. Elective operation is indicated in all patients with
      popliteal artery aneurysm, and it is associated with a relatively low risk for
      the patient. In fact, it is a preventive operation. In the acute stage, there is
      a higher risk of complications and (potential) amputation (Fig. 1, Ref. 8).

PMID- 16642670
TI  - Secular rhythms and Halberg's paraseasonality in the time occurrence of cerebral
      stroke.
AB  - OBJECTIVES: To obtain the optimal information concerning the time course of the
      morbidity od cerebral stroke. BACKGROUND: Recently, long years' cycling, similar
      to that in sun and geomagnetic activity, is observed in various biomedical
      variables. Other discovery is that of transyear (over one year) and cisyear
      (under one year) rhythms,originating also in the sun, in medicine. SUBJECTS:
      There were 6100 patients with cerebral infarction, 415 with intracerebral and 277
      with subarachnoid hemorrhage admitted at Clinic of Neurology in Nove Zamky (area
      with 70 km radius and 180 000 inhabitants). Their monthly numbers were registered
      since January 1989 up to December 2004. METHODS: The data were processed by
      Halberg's cosinor regression. Presence of linear trend and of the period lengths
      of 10.5 (solar Schwabe-cycle), 5.25, 7.04 (geomagnetic activity cycling), 3.52,
      1.70, 1.50, 1.30 (solar wind cycling), 1.20, 1.00 and 0.50 years was tested.
      Level of statistical significance was set at alpha = 0.05. RESULTS: In all three
      time series, significant linear trends were found with the estimated monthly
      increase by 0.8% of the estimated starting mesor value for infarction, 1.2% for
      cerebral and 1.9% for subarachnoid hemorrhage. Both the solar and geomagnetic
      cycling with their second harmonics were significant in all three clinical
      diagnoses. The transyear with period length of 1.3 year was significant in both
      hemorrhages while in infarction only its borderline significance was achieved.
      Nevertheless, its amplitude was always higher (by 15 to 83%) than that of 1.00
      year estimated cosinusoid. CONCLUSION: All presented time series document
      increasing trends in the morbidity on cerebral stroke in the given geographic
      area. The presence of secular, years lasting cycles adds to relatively long list
      of similar chronocosmoepidemiologic analyses, so far generally ignored due to
      insufficient understanding of inferential statistics and chronobiology among
      doctors. The transyear paraseasonality represents a new element in these studies.
      To honour the nestor of the world chronobiology, who highly acknowledged the work
      of Ladislav Derer, the designation "Halberg's paraseasonality" is proposed (Tab.
      2, Fig. 3, Ref. 17).

PMID- 16642672
TI  - Blog day afternoon.

PMID- 16642671
TI  - 21st century manager imperatives.

PMID- 16642673
TI  - Handling BBP requirements in manufacturing and service industries.

PMID- 16642674
TI  - How state medical marijuana laws affect workplace drug testing.

PMID- 16642675
TI  - The everyday hearing protection program.

PMID- 16642676
TI  - Health care workers' crucial barriers.

PMID- 16642677
TI  - Building arc flash awareness.

PMID- 16642678
TI  - More grip, less force.

PMID- 16642679
TI  - Dexterity in work gloves--a touchy subject.

PMID- 16642681
TI  - High-level cooperation.

PMID- 16642680
TI  - Young and old: why one-size fits all doesn't work.

PMID- 16642682
TI  - Confined space entry, part 3.

PMID- 16642683
TI  - A recycling option.

PMID- 16642684
TI  - Watch out for multiple MSDs.

PMID- 16642685
TI  - A smarter way to sit.

PMID- 16642686
TI  - Person-centered planning training for consumer-directed care for the elderly and
      disabled.
AB  - Based on the need for a training program for person-centered planning SC Choice,
      a Real Choice/Independent Living Grant, included the development of training
      materials and a training program for the implementation of the transformation
      from agency case manager to care advisor. The development of this training
      included receiving the person-centered planning training currently used by the
      developmentally disabled agencies, as well as interviews and focus groups with
      interested staff and participants. A training program for the Elderly/Disabled
      Waiver population using adult learning techniques is described in detail Included
      in this training are the philosophy, the activities, and the necessary steps to
      complete person-centered planning for the transition of a case manager to a care
      advisor in a consumer-directed program for the elderly.

PMID- 16642687
TI  - Variations in care management arrangements for people with mental health problems
      in England.
AB  - Since 1989, government policy in the United Kingdom has advocated that social
      services providers develop care management systems in order to deliver
      coordinated and individually tailored packages of care to all user groups. This
      cross-sectional postal survey describes national variations in care management
      arrangements for people with mental health problems in England on 14 key
      indicators developed from previous research. One hundred and one social services
      providers (response rate: 77%) completed two questionnaires: The first related to
      care management arrangements for all user groups, and the second related
      specifically to arrangements for people with mental health problems. Significant
      national variation was found. Furthermore, there was little evidence of
      integration between health and social care, of care management being delivered
      through specialist multidisciplinary mental health teams, and of selective
      arrangements targeted at those most in need. The results are discussed in the
      context of apparently widespread disparity between existing care management
      arrangements and government policy guidance.

PMID- 16642688
TI  - Self-esteem and stigma among persons with schizophrenia: implications for mental
      health.
AB  - The purpose of the study was to examine the relationship between perceived stigma
      and self-esteem among adults with schizophrenia. The sample was drawn from three
      outpatient public mental health clinics in Southern California in September to
      November 2002. The following selection criteria were used to identify 31
      respondents: (1) a diagnosis of schizophrenia and (2) stable symptoms. Self
      esteem was measured using the Rosenberg Self-Esteem Scale. Stigma was measured
      using the Devaluation-Discrimination Measure. The strongest areas of stigma
      reported by those surveyed were related to hospitalization. The self-esteem of
      the respondents was moderately high. A Pearson's r correlation indicated that
      there was a significant, moderately strong correlation, with a higher level of
      perceived stigma associated with a lower level of self-esteem. Findings suggest
      that using a strengths-based approach and a recovery case management model is
      recommended to decrease stigma and promote self-esteem among persons with
      schizophrenia.

PMID- 16642689
TI  - Interpreting senility: cross-cultural perspectives.
AB  - In general, senility in American society is seen through the lens of biomedicine
      and conceptualized in terms of physical changes in the person. Research on
      attitudes about senility in other cultures shows that this is not the only way to
      conceptualize cognitive change in later life. This article explores cultural
      aspects related to cognitive change in old age by focusing on ethnographic
      examples from Japan. I argue that in Japan the social concepts related to
      defining the person are emphasized when thinking about cognitive change in later
      life, rather than biomedical concepts associated with pathologies of the brain.
      In part because of this focus, for older Japanese senility is often viewed as
      being a moral category as much as a category of disease.

PMID- 16642690
TI  - 6.4 million at risk: protecting the poorest Americans during the Medicare drug
      transition.

PMID- 16642691
TI  - The caregiver balancing act: giving too much or not enough.
AB  - Although there are many reasons why an individual becomes a caregiver, there are
      even more ways for a caregiver to suffer "burnout," which can endanger his or her
      well-being and limit the ability to provide adequate care to another. This
      article provides a summary of the manner in which an individual may approach
      caregiving, the reasons for becoming a caregiver, the causes of caregiver fatigue
      and burnout, and the liability that a caregiver may face if he or she does not
      provide adequate care. Additionally, this article will discuss federal and state
      programs to assist caregivers, as well as recommendations for public policies and
      programs to help caregivers and protect the individuals in need of care.

PMID- 16642692
TI  - [Preventing hypertension with drugs?].

PMID- 16642693
TI  - [In high risk patients also treat high normal blood pressure values!].

PMID- 16642694
TI  - [7 causes of therapy refractory hypertension].

PMID- 16642695
TI  - [Later on risk of sudden cardiac death is doubled].

PMID- 16642696
TI  - [Meditation for heart conditions].

PMID- 16642697
TI  - [Sweat treatment for failing hearts].

PMID- 16642698
TI  - [Is your patient MRSA (multi-resistent Staphylococcus aureus) free?].

PMID- 16642699
TI  - [Lack of insurance was not the issue].

PMID- 16642700
TI  - [Where is the pain in the shoulder coming from? (interview by Dr. Judith
      Neumaier)].

PMID- 16642701
TI  - [Life-threatening emergency or merely psychosomatic? The art of interpreting
      abdominal pain].

PMID- 16642702
TI  - [Presenting problem: abdominal pain].
AB  - The Saxon Study for General Medicine (SESAM) investigated the reasons why
      patients consulted the general physician, what diagnoses were established, and
      how the patients were subsequently treated. In the majority of cases, the reason
      for the abdominal complaints was located in the gastrointestinal or urogenital
      tract, in the presence of infections or psychosomatic problems. Gynecological
      problems must also be considered, while diseases other than gastrointestinal are
      of no significance for the differential diagnosis of abdominal complaints in the
      general physician's office.

PMID- 16642703
TI  - [Diagnostic work-up of abdominal pain by the family doctor: an avertable
      potentially threatening situation must be excluded].
AB  - When patients attend the physician's office with acute abdominal pain, the doctor
      must first exclude a potentially dangerous condition (acute abdomen) before
      initiating symptomatic treatment (e. g. painkilling drugs). The need for this is
      based in the first instance on the presence of severe complaints in combination
      with the absence of a plausible explanation for the patient's distress, as well
      as, secondarily, the anxiety of the patient or the person accompanying him, or
      even the doctor's own anxiety about possibly overlooking a serious pathology.

PMID- 16642704
TI  - [Red, yellow, green: management of gastrointestinal complaints].
AB  - In a patient presenting with acute abdominal pain, initiation of symptomatic
      treatment must be preceded by the reliable exclusion of a potentially serious
      situation (acute abdomen = red light). Rapidly progressive or severe abdominal
      pain mandates an urgent diagnostic investigation on the part of the physician. No
      less important is the positive diagnosis of psychosomatic disorders (yellow
      light). If the family doctor fails to properly counsel the patient, too much
      diagnostic effort can lead to an iatrogenic somatic fixation. In the absence of
      all the above, the light shows green for causal therapy, an open mind on the
      diagnosis, symptomatic treatment and follow-up.

PMID- 16642705
TI  - [Antiandrogen therapy of prostate carcinoma].
AB  - Thanks to improved examination techniques, many cases of prostate cancer are now
      being diagnosed in younger patients. It is therefore of ever greater importance
      that treatment should have no great impact on the patient's quality of life.
      Nonsteroidal antiandrogens have a more favorable side effect profile than
      surgical or pharmacological castration, since the serum concentration of
      testosterone remains within the normal range. Depending on the stage of the
      illness, they can be employed in the form of monotherapy as an adjuvant to
      prostatectomy or radiotherapy in local advanced prostate cancer, and as
      components of maximum androgens blockade.

PMID- 16642706
TI  - [Laparoscopic appendectomy--a lot of effort for a minor operation?].
AB  - In the hands of an experienced surgeon, laparoscopic appendectomy is by no means
      a time-consuming procedure that might put the patient at risk. In particular it
      enables an all round inspection of the abdominal cavity, thus enabling both the
      detection of diverticular disease and tumors or processes within the true pelvis.
      The complication-free operation leaves behind only tiny scars, so that, in the
      event of abdominal complaints at some later date, a mistaken diagnosis of
      appendicitis might easily be established elsewhere. To help prevent this, the
      patient must be given the relevant information about the procedure. In addition,
      provision of the patient with a medical ID card is proposed.

PMID- 16642707
TI  - [AT1 receptor antagonist lorsartan and organ protection. Managing hypertension a
      different way].

PMID- 16642708
TI  - [Side-effects of EBM 2000plus: dissident general practitioners punished with
      fees].

PMID- 16642709
TI  - [Hopefully he will still practice for a long time!].

PMID- 16642710
TI  - [Significant thoracic pain after vomiting].

PMID- 16642711
TI  - [Suspected multiple sclerosis].

PMID- 16642712
TI  - [SAPHO and the knee].

PMID- 16642713
TI  - Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.
AB  - The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism
      by atipamezole was evaluated for reversible anaesthesia of free-ranging lions
      (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males
      and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at
      0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32
      mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses
      were gradually decreased to improve recovery. Respiratory and heart rates, rectal
      temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every
      15 min. Arterial blood samples were collected from 5 lions for analysis of blood
      gases and acid-base status. For anaesthetic reversal, atipamezole was
      administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth
      and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min
      after darting. The predictable working time was a minimum of 1 h and no
      additional drug doses were needed. Respiratory and heart rates and SpO2 were
      stable throughout anaesthesia, whereas rectal temperature changed significantly
      over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for
      reversal and recoveries were smooth and calm in all lions independent of the
      atipamezole dose. First sign of recovery was observed 3-27 min after reversal.
      The animals were up walking 8-26 min after reversal when zolazepam-tiletamine
      doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80
      mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for
      either sex of an adult or subadult lion. The drugs and doses used in this study
      provided a reliable, safe and reversible anaesthesia protocol for free-ranging
      lions.

PMID- 16642714
TI  - Efficacy of orally administered powdered aloe juice (Aloe ferox) against ticks on
      cattle and ticks and fleas on dogs.
AB  - The efficacy of orally administered powdered aloe juice (Aloe ferox) was
      evaluated against ticks on cattle and against ticks and fleas on dogs. Twelve
      calves were each infested over a 25-day period with approximately 4000 larvae of
      Rhipicephalus (Boophilus) decoloratus and allocated to 3 groups of 4 calves each.
      Three days after the last larval infestation and daily for 22 days thereafter,
      the calves in 1 group were fed 5 mg/kg body weight and those in another 25 mg/kg
      body weight of powdered aloe juice incorporated in game maintenance pellets,
      while the animals in the 3rd group received only pellets. Detached female ticks
      were collected daily and counted and the weights and the fertility of groups of
      50 engorged female ticks collected from the animals were ascertained. The
      powdered aloe juice in the game maintenance pellets had no effect on the tick
      burdens of the calves or on the fertility of the ticks. Six dogs, in each of 2
      groups, were treated daily for 15 consecutive days, commencing on Day -5 before
      the 1st tick infestation, with either 0.39 g or 0.74 g of powdered aloe juice,
      administered orally in gelatin capsules, while a 3rd group of 6 dogs served as
      untreated controls. All the dogs were challenged with Haemaphysalis leachi on
      Days 0 and + 7, and with Ctenocephalides felis on Days + 1 and + 8, and efficacy
      assessments were made 1 day after flea and 2 days after tick challenge,
      respectively. Treatment was not effective against ticks or fleas on the dogs.

PMID- 16642715
TI  - Ulcerative balanitis and vulvitis of Dorper sheep in South Africa: a study on its
      aetiology and clinical features.
AB  - Ovine ulcerative balanitis and vulvitis in sheep of the Dorper breed has been
      observed in South Africa since 1979. Its aetiology has not been conclusively
      resolved, and there is some discrepancy in descriptions of its clinical features.
      In order to identify the pathogenic micro-organism/s that contribute to the
      occurrence of the disease, the microflora in the genital tracts of both
      clinically healthy and affected sheep were isolated and compared. Bacteriological
      examination of materials from affected and unaffected sheep resulted in the
      isolation of Arcanobacterium pyogenes from 44.2% and 17.2% of them respectively.
      This difference is statistically significant (P < 0.01). Seventy-four per cent of
      the isolates originated from severe clinical cases. Mycoplasmas were isolated
      from 49.3% of 116 clinically normal sheep and 78.2% of 104 affected sheep. There
      were significant differences in their rates of isolation in clinical groups (P <
      0.05). Of all the mycoplasma isolates, Mycoplasma mycoides mycoides large colony
      variant (MmmLC) was isolated from 61.5% of clinically diseased sheep while 6.0%
      of the isolates were from apparently healthy animals (P < 0.05). The study threw
      light on the prevalence of mycoplasmas in the genital tract of apparently healthy
      sheep and, at the same time the identity of the mycoplasma pathogen associated
      with ulcerative balanitis and vulvitis was revealed. The findings of this
      investigation therefore confirmed the involvement of mycoplasma, particularly
      that of MmmLC large colony, in the disease in Dorper sheep in South Africa, and
      it was concluded that this microorganism is an important pathogen of balanitis
      and vulvitis in them. The study furthermore demonstrated a probable synergism
      between A. pyogenes and MmmLC. Finding these 2 organisms together occurred 53.4
      times more frequently in the affected sheep than in the unaffected, which
      emphasises the probable multifactorial nature of the disease. The association
      between age and the presence of clinical signs was statistically significant. It
      was found that young sheep were more likely to have lesions than adult sheep.
      Clinical observations showed that the typical ulceration appears to be confined
      to the glans penis and lips of the vulva; no ulceration was observed on the shaft
      of the penis and prepuce or vaginal vestibule. In uncomplicated cases
      inflammation of the prepuce and vaginal vestibule is not a regular feature of the
      disease. Therefore the names ulcerative balanitis and vulvitis most accurately
      describe the nature of the disease in South Africa.

PMID- 16642716
TI  - In vitro antimicrobial susceptibility of Mycoplasma mycoides mycoides large
      colony and Arcanobacterium pyogenes isolated from clinical cases of ulcerative
      balanitis and vulvitis in Dorper sheep in South Africa.
AB  - The in vitro activities of enrofloxacin, florfenicol, oxytetracycline and
      spiramycin were determined against field isolates of Mycoplasma mycoides mycoides
      large colony (MmmLC) by means of the broth microdilution technique. The minimum
      inhibitory concentrations (MICs) of these antimicrobial drugs were determined for
      a representative number of 10 isolates and 1 type strain. The susceptibility of
      Arcanobacterium pyogenes to enrofloxacin, oxytetracycline and tilmicosin was
      determined by means of an agar disk diffusion test. The MICs of enrofloxacin,
      florfenicol, oxytetracycline and spiramycin were within the ranges of 0.125-0.5,
      1.0-2.0, 2.0-4.0 and 4.0-8.0 microg/ml, respectively. This study has shown that
      resistance of MmmLC against enrofloxacin, florfenicol, oxytetracycline and
      spiramycin was negligible. All the field strains of A. pyogenes that were tested
      were susceptible to enrofloxacin, oxytetracycline and tilmicosin with mean
      inhibition zones of 30.6, 42.3 and 35.8 mm, respectively. Although there is lack
      of data on in vivo efficacy and in vitro MIC or inhibition zone diameter
      breakpoints of these antimicrobial drugs for MmmLC, the MIC results indicate that
      these 4 classes of antimicrobial drugs should be effective in the treatment of
      ulcerative balanitis and vulvitis in sheep in South Africa.

PMID- 16642717
TI  - Participatory rural appraisal to investigate constraints in reporting cattle
      mortalities in the Odi district of North West Province, south Africa.
AB  - Mortalities in cattle can have severe financial implications for small scale and
      communal farmers in South Africa. They could also be a measurable indicator for
      surveillance of animal diseases, such as those listed by the Office International
      des Epizooties (OIE), or diseases included in the regulations of the South
      African Animal Diseases Act, 1984 (Act 35 of 1984). In order to prevent further
      mortalities and for accurate surveillance and monitoring of diseases, it is
      important that farmers participate in the determination of causes of mortality in
      their cattle. This paper reports on constraints of the reporting diseases to the
      state veterinary services, the study area being Odi district, in the North West
      Province. The method that was followed was based on participatory rural
      appraisal. The selected cattle owners participated in every phase. They were the
      ones who first spoke to veterinary services about ways to decrease the diseases
      and mortalities of their cattle. A questionnaire to verify the facts complemented
      the survey. A total number of 60 farmers were randomly selected from 12 villages.
      One farmer withdrew, leaving 59 farmers. Most of the farmers in the study were
      men ( n = 55). The area of study was communal and the farming system traditional
      and extensive. It was suspected that there was a communication problem and this
      was proven by the results of the research, as 23 farmers were not even aware that
      mortalities have to be reported by law. The real problem was that causes of death
      were not being diagnosed because farmers were not aware that a necropsy could
      give information on the causes of death. Farmers were keen to receive training in
      elementary necropsy techniques so as to be able to discuss the cause of death of
      cattle with the state veterinarian.

PMID- 16642718
TI  - Efficacy of parenteral administration of ivermectin in the control of
      strongylidosis in donkeys.
AB  - Investigations into the efficacy of parenteral ivermectin (Pandex) administration
      for strongylidosis control in donkeys were carried out. The preparation was
      applied subcutaneously at a dose of 0.2 mg/kg (1 ml/50 kg body weight). One day
      prior to the treatment and 14 days post-treatment, individual coprological
      samples were obtained for faecal nematode egg counts and larval culture. The
      study was performed on 263 donkeys originating from different regions of
      Bulgaria. Prior to the treatment and 20 days after that, blood samples were
      obtained from 64 previously infected animals for monitoring of changes in
      eosinophil leukocyte counts. The subcutaneous application of ivermectin had an
      efficacy of 96% in terms of reduction of faecal egg counts. In 92.2% of infected
      donkeys, a complete reduction of faecal eggs count occurred (0 eggs per gram of
      faeces epg), whereas in the remaining 7.8% of the infected donkeys, the egg
      counts were reduced by 72%. The reduction in faecal egg counts did not result in
      changes in eosinophil counts. The results obtained as well as the lack of local
      changes after the subcutaneous application of ivermectin in donkeys allow us to
      recommend its use for control of strongyles in donkeys.

PMID- 16642719
TI  - The impact of 2 dipping systems on endemic stability to bovine babesiosis and
      anaplasmosis in cattle in 4 communally grazed areas in Limpopo Province, South
      Africa.
AB  - A 12-month study was conducted in 4 communal grazing areas in the Bushbuckridge
      region, Limpopo Province, South Africa. The main objective was to investigate the
      impact of reduced acaricide application on endemic stability to bovine babesiosis
      (Babesia bigemina and Babesia bovis) and anaplasmosis (Anaplasma marginale) in
      the local cattle population. To this end 60 cattle in each communal grazing area
      were bled at the beginning and the conclusion of the experimental period and
      their sera were assayed for B. bovis, B. bigemina and Anaplasma antibodies.
      Cattle in the intensively dipped group were dipped 26 times and maintained on a
      14-day dipping interval throughout the study, whereas cattle in the strategically
      dipped group were dipped only 13 times. Three cattle, from which adult ticks were
      collected, were selected from each village, while immature ticks were collected
      by drag-sampling the surrounding vegetation. During the dipping process, a
      questionnaire aimed at assessing the prevalence of clinical cases of tick-borne
      disease, abscesses and mortalities was completed by an Animal Health Technician
      at each diptank. An increase in seroprevalence to B. bovis and B. bigemina and a
      decrease in seroprevalence to Anaplasma was detected in the strategically dipped
      group while in the intensively dipped group the converse was true. Amblyomma
      hebraeum was the most numerous tick species on the cattle, and Rhipicephalus
      (Boophilus) microplus was more plentiful than Rhipicephalus (Boophilus)
      decoloratus. Drag samples yielded more immature stages of A. hebraeum than of
      Rhipicephalus (Boophilus) spp. The incidence of clinical cases of tick-borne
      disease and of abscesses increased in the strategically dipped group at the start
      of the survey.

PMID- 16642720
TI  - Prevalence of genital campylobacteriosis and trichomonosis in crossbred breeding
      bulls kept on zero-grazed smallholder dairy farms in the Tanga region of
      Tanzania.
AB  - A survey to demonstrate the presence or absence of genital campylobacteriosis and
      trichomonosis in cross-bred breeding bulls kept under smallholding dairy farms in
      the Tanga region of Tanzania was carried out during the period of January-June
      1996. Sheath washings, swabs and preputial scrapings were collected from 58
      randomly selected bulls. Campylobacter fetus subsp. venerealis was demonstrated
      in 3/58 (5.1%) and Tritrichomonas foetus in 0/58 (0%) of all bulls tested. Bull
      level variables of level of taurine genes (62.5% taurine genes, F2; 75% taurine
      genes, F3) and age were not significantly associated with campylobacteriosis (P >
      0.05). The result of the study identifies Campylobacterfetus subsp. venerelias as
      the agent of enzootic infertility in smallholder herds and suggests that may be a
      significant problem.

PMID- 16642721
TI  - Cryptococcus neoformans granuloma in the lung and spinal cord of a free-ranging
      cheetah (Acinonyx jubatus). A clinical report and literature review.
AB  - A 6-year-old, male, wild-born, free-ranging cheetah (Acinonyx jubatus) was
      evaluated for acute onset of progressive lameness in the right hind limb. Survey
      radiographs were unrewarding and myelography indicated an intramedullary
      compressive mass at the L3-L4 region. A fine needle aspirate of the lesion
      indicated the presence of Cryptococcus organisms. Necropsy confirmed the presence
      of granulomas (cryptococcoma) in the lung and the spinal cord (meningomyelitis)
      caused by Cryptococcus neoformans var. gattii. Cryptococcus neoformans is a yeast
      like organism that is a potential pathogen to many species. Initial infection is
      thought to be of respiratory origin and then it commonly disseminates
      systemically from the nasal cavity or lungs to the skin, eyes and central nervous
      system in particular. The cheetah tested negative for both feline leukaemia virus
      (FeLV) and feline immunodeficiency virus (FIV), as have all the previously
      reported cheetah cases. C. neoformans is a non-contagious, opportunistic organism
      and is the most common systemic mycoses in domestic cats and the cheetah.

PMID- 16642722
TI  - Katkor cat litter, a non-invasive method of collecting cat urine for phosphate
      determination.
AB  - This study was done to compare the collection of cat urine, for phosphate
      concentration determination, by catheterisation with that via a proprietary cat
      litter (Katkor). The passage of urine through the litter or its retention in the
      litter for a period of 2 hours did not affect the concentration of phosphates
      compared with that of the original sample. Apart from a small volume of urine
      trapped in the litter by capillary action, and some urine adhering to the funnel
      in which the litter was placed, the litter proved to be an excellent medium for
      routine urine collection from cats, and more especially as an alternative to
      catheterisation when regular collection from a particular cat is required.

PMID- 16642723
TI  - Genomic analyses of the evolution of LGR genes.
AB  - Recent completion of the sequencing of genomes from several mammals, teleosts and
      invertebrates has shown that G protein-coupled receptors (GPCRs) are one of the
      conserved groups of cell surface receptors with an ancient origin. GPCRs play
      important roles in diverse physiological functions and are the most important
      targets for pharmaceutical discoveries. Recent work based on the search for gene
      with structural similarity to LH, FSH and thyroid-stimulating hormone (TSH)
      receptors in diverse genomes has led to the identification of a group of GPCRs
      called Leucine-rich repeat-containing, G protein-coupled Receptor (LGR). We
      present the genomic analyses of the evolution of LGR genes in the literature.

PMID- 16642724
TI  - Embryo-endometrial interaction.
AB  - Embryonic implantation, the process by which the human embryo orientates towards,
      attaches to and finally invades the underlying maternal endometrial tissue,
      requires a receptive endometrium, a functionally normal blastocyst and an
      adequate cross-communication between them. During apposition, human blastocysts
      find a location in which to implant, while they are guided to a specific area in
      the maternal endometrium. In the adhesion phase, which occurs 6 to 7 days after
      ovulation, within the so-called "implantation window", direct contact occurs
      between the endometrial epithelium (EE) and the trophectoderm (TE). Finally, in
      the invasion phase, the embryonic trophoblast traverses the basement membrane and
      passes the endometrial stroma and reaches the uterine vessels. Many molecules
      (hormones, cytokines, integrins, enzymes, etc.) take part in the dialogue between
      the human blastocyst and the maternal endometrium to achieve implantation. Here,
      we present our published data on the embryonic regulation of endometrial
      epithelial molecules such as chemokine receptors and the leptin system.

PMID- 16642725
TI  - Applications of microarray in reproductive medicine.
AB  - In the genomic era, cDNA microarray (DNA chip) technology has become a very
      important and powerful tool for high-throughput comprehensive analysis of gene
      expression, genotyping and re-sequencing applications in almost every field of
      biomedical research. Large-scale transcriptional profiling analyses using
      microarrays are frequently used to explore gene expression patterns in order to
      better understand the molecular mechanisms of physiology and pathogenesis: these
      are the basis for the development of new diagnostic and therapeutic strategies.
      Recently, this powerful technique has been used with laser capture
      microdissection (LCM) and linear aRNA amplification (in vitro transcription), and
      used in reproductive medical research. Recent studies of microarray-related
      techniques used to study oocyte fertilization, early embryo development,
      implantation and some infertility-related diseases (endometriosis and myoma) are
      discussed and summarized in this review.

PMID- 16642726
TI  - The cytokine network during embryo implantation.
AB  - Embryo implantation is an essential step in mammalian pregnancy. The molecular
      events of embryonic attachment to the endometrial epithelium and the subsequent
      invasion of the stroma have long been of interest. The process involves both the
      scientific interest of reproductive biologists and clinical interest of
      physicians that care for infertility couples. Understanding the molecular factors
      involved in each phase of the implantation process is critical to comprehending
      the mechanisms that control reproduction, especially as part of a human in vitro
      fertilization program. This review will focus on the role during early embryonic
      development and implantation of two distinct cytokines, the interleukin-1 (IL-1)
      system and interleukin-18 (IL-18) system; it will also examine the role of the
      matrix metalloproteinases (MMP) and their inhibitors as well as vascular
      endothelial growth factor (VEGF) system. The possible influence of the cytokines
      on other systems involved in embryonic implantation, including the embryonic
      endometrial dialogue, the subsequent invasion and neoangiogenesis will be
      discussed. These suggest a role for the two cytokine families in early embryonic
      development.

PMID- 16642727
TI  - The emerging functionality of endogenous lectins: A primer to the concept and a
      case study on galectins including medical implications.
AB  - Biochemistry textbooks commonly make it appear that it is a foregone conclusion
      that the hardware of biological information storage and transfer is confined to
      nucleotides and amino acids, the letters of the genetic code. However, the
      remarkable talents of a third class of biomolecules are often overlooked. For
      example, one of them far surpasses the building blocks of nucleic acids and
      proteins in terms of theoretical coding capacity by oligomer formation. Although
      often exclusively assigned to duties in energy metabolism, carbohydrates as part
      of cellular glycoconjugates (glycoproteins, proteoglycans, glycolipids) have, in
      fact, other important tasks. Currently, they are increasingly gaining recognition
      as an operative high-density information coding system. An elaborate enzymatic
      machinery enables cells to be versatile enough to produce a glycan profile
      (glycome) that is as characteristic as a fingerprint. Moreover, swift
      modifications during dynamic processes, such as differentiation or malignant
      transformation, are readily possible. The translation of the information
      presented in oligosaccharide determinants to biological responses is carried out
      by lectins. Recognition of foreign glycosignatures in innate immunity, regulation
      of cell-cell/matrix interactions, cell migration or growth, and intra- and
      intercellular glycan routing etc represent physiologically far-reaching lectin
      carbohydrate functionality. The classification of endogenous lectins is guided by
      sequence alignments and conservation of distinct structural traits. For example,
      a jelly-roll-like folding pattern and maintenance of key residue positioning
      involved in stacking and C-H/pi-interactions as well as directional hydrogen
      bonds to the 1-galactoside ligands are common denominators among galectins.
      Biochemical and biophysical studies are beginning to unravel the intricacies of
      the selection of a limited set of endogenous ligands, such as certain integrins
      or ganglioside GM1, and combined with biological cell experiments, its relevance
      for cell sociology, e.g. in growth regulation and tumor cell invasion or
      activated T cell apoptosis. Histopathological monitoring accompanies the
      biological cell investigations, linking expression of certain family members to
      tumor progression or suppression. Further insights into the functional
      consequences of the sugar code's translation are thus expected to have notable
      repercussions for diagnostic and therapeutic procedures.

PMID- 16642728
TI  - Schisandra chinensis protects against adriamycin-induced cardiotoxicity in rats.
AB  - BACKGROUND: Adriamycin (ADR) is an effective chemotherapeutic agent against
      cancers but its clinical use is limited due to its cardiotoxicity. It has been
      suggested that the pathogenesis involves inhibition of nucleic acid and protein
      synthesis, free radical formation and lipid peroxidation. Schisandra (SC) has
      strong antioxidant activity. We investigate the protective effects of SC on
      adriamycin-induced cardiotoxicity. METHODS: Wistar rats were divided into four
      groups: CONT (control), ADR, SC and SC + ADR. After treatment, the hearts of the
      rats were surgically removed and studied for synthesis rates of nucleic acid and
      protein, myocardial antioxidants and lipid peroxidation. RESULTS: Cardiotoxicity
      was characterized by ascites, congested liver and depressed cardiac function.
      Nucleic acid and protein synthesis were inhibited, malondialdehyde (MDA) was
      increased, while myocardial glutathione peroxidase (GSHPx) activity and
      superoxide dismutase (SOD) were decreased by ADR. In contrast, administration of
      SC before and concurrent with ADR significantly reduced mortality and the amount
      of ascites. Indexes in myocardial GSHPx, macromolecular biosynthesis and SOD
      activities increased with a concomitant decrease in lipid peroxidation.
      CONCLUSION: These results suggest that ADR cardiotoxicity is associated with
      antioxidant deficit and SC treatment changes the antioxidant status of the heart
      and improves cardiac function.

PMID- 16642729
TI  - Surgical treatment for giant cell tumor of the thoracolumbar spine.
AB  - BACKGROUND: Giant cell tumor (GCT) of the bone has historically been regarded as
      an extremely unpredictable bone tumor. The anatomical characteristics of spinal
      GCT still present challenges to surgeons. Controversy remains regarding the
      proper treatment of patients with grade III tumors. METHODS: Eleven patients with
      grade III GCT of the thoracolumbar spine were treated between 1992 and 2002 at a
      medical center by the authors. Three patients were initially treated at other
      institutions. Adjuvant radiotherapy was employed for local recurrence in these
      three patients. The other eight patients were initially treated with marginal
      excision. The site, size, and extent of each lesion dictated the surgical
      approach. RESULTS: Five patients had tumor recurrence. One patient, who received
      radiotherapy, had local relapse with malignant transformation and finally died
      due to disease-related complications. One patient had a recurrent tumor with
      multiple metastases throughout the lung. Neurological status, measured using the
      American Spinal Injury Association scale, of one patient was worse after
      undergoing the procedure than preoperatively and three patients showed
      improvement. The other seven patients were classified as with the same grade
      postoperatively. CONCLUSION: Wide excision of GCT of the thoracolumbar spine is
      difficult and there is a risk of neurological deficit and spinal instability.
      Meticulous marginal excision with associated reconstruction may obtain good local
      control and preserve functional spine. Early detection of recurrent GCT during
      intensive follow-up can allow for treatment using en bloc excision which has
      achieved favorable prognoses.

PMID- 16642730
TI  - Ipsilateral femoral neck and shaft fractures treated with Russell-Taylor
      reconstruction intramedullary nails.
AB  - BACKGROUND: Ipsilateral femoral neck and shaft fractures are rare injuries and
      the treatment is complicated and versatile. No single device has been considered
      absolutely superior to others. METHODS: Fifteen combined fractures in 15 patients
      were treated with Russell-Taylor reconstruction intramedullary nails (recon
      nails). Twelve surgeries were performed within 24 hours of trauma and the other 3
      were delayed for 4-7 days due to associated life-threatening injuries.
      Postoperatively, protected weight bearing was permitted as early as possible.
      RESULTS: The median operating time was 250 minutes (range 125-430 min) and median
      blood loss was 300 ml (range 100-600 ml). Thirteen patients were followed-up for
      a median of 22 months (range 13-45 months). The union rates for neck and shaft
      fractures were 84.6% and 69.2% respectively. The median union times were 3.0
      months for neck fractures and 8.5 months for shaft fractures. CONCLUSIONS: Recon
      nails are alternative acceptable devices to treat combined fractures. However,
      the stability of neck fixation may be insufficient and restriction of vigorous
      activity is suggested to avoid fixation failure.

PMID- 16642731
TI  - Complications of hip arthroscopy: analysis of seventy three cases.
AB  - BACKGROUND: Hip arthroscopy is recognized as a highly effective means of treating
      joint disorders. Complications in hip arthroscopy, including neurovascular
      traction injury, compression injury to the perineum and scope trauma, have been
      reported. We report our experience with 73 hip arthroscopy procedures and
      complications at Chang Gung Memorial Hospital. METHODS: Seventy-two patients with
      73 hips with severe hip pain were enrolled in this prospective study. The average
      age of the patients was 42 years (range, 22-61 years). The average follow-up
      period was 16 months (range, 12-36 months). Surgical indications for hip
      arthroscopy were labral tears (54 cases, 73.9%); painful dysplastic hips (7
      cases, 9.5%); osteoarthritis (5 cases, 6.8%); synovitis (3 cases, 4.1%); ligament
      teres tears (2 cases, 2.8%); chondromatosis (1 case, 1.4%); and avascular
      necrosis of the femoral head (1 case, 1.4%). With the patient in the supine
      position with the involved leg in traction, 2 or 3 portals (anterior,
      anterolateral or posterolateral) were made. Intraoperative and postoperative
      arthroscopic complications were recorded and prospectively analyzed. RESULTS: The
      average operative time was 67 minutes (range, 30-190 minutes) and the average
      traction time was 58 minutes (range, 30-150 minutes). During surgery, 12 of 73
      (16.4%) patients had mild scope trauma to the femoral head, which did not affect
      their excellent outcomes. Five (7%) patients had transient sciatic nerve
      neuropraxia and achieved complete recovery within 2 weeks after surgery.
      CONCLUSION: No major complications of hip arthroscopy were noted in this series.
      The most frequent complication was mild scope trauma to the femoral head. With
      experience in the technique and good hip arthroscopic instrumentation, hip
      arthroscopy complications can be minimized. We suggest that hip arthroscopy is a
      safe technique, providing an additional valuable tool for hip surgery.

PMID- 16642732
TI  - Transforaminal epidural steroid injection for discectomy candidates: an outcome
      study with a minimum of two-year follow-up.
AB  - BACKGROUND: The efficacy of epidural steroid injection for sciatica due to
      herniated disc is controversial. This study evaluates the therapeutic effect of
      an alternative technique that uses a modified approach of epidural steroid
      injection for the above mentioned disease. The aim was to determine whether this
      procedure can reduce the need of surgery among discectomy candidates. METHODS:
      Twenty-one eligible patients who had suffered from sciatica with unilateral
      symptoms for 2 to 24 months received injections of betamethasone in combination
      with xylocaine. The treatment outcome was evaluated by direct questioning and
      examination using the JOA score (the criteria for low back pain syndrome of
      Japanese Orthopaedic Association) before the procedure and at the final follow-up
      visit. The final analysis comprised 19 patients with a minimum of 24-month follow
      up. RESULTS: The overall JOA score increased significantly from 14.26 +/- 3.25
      before injection to 23.38 +/- 4.46 after injection showing improvement. In terms
      of subcategories, the JOA score for sciatica increased significantly from 0.69 +/
      0.48 before infection to 2.13 +/- 0.72 after injection and the JOA score for
      daily activity increased significantly from 7.44 +/- 2.16 before injection to
      12.19 +/- 2.23 after injection). In the end, three treated patients received
      surgical decompression for intractable recurrent pain. CONCLUSIONS:
      Transforaminal epidural steroid injection is a relatively simple, effective and
      low-risk alternative to surgical decompression for the treatment of lumbar disc
      herniation in selected cases. The procedure significantly alleviates the severity
      of sciatica due to a herniated disc and improves the patient's daily activity;
      this reduces the need for surgical decompression.

PMID- 16642733
TI  - The effectiveness of an aerobic exercise intervention on worksite health-related
      physical fitness--a case in a high-tech company.
AB  - BACKGROUND: The major objective of this prospective study was to evaluate the
      effects of aerobic exercise intervention with goals of improving health-related
      physical fitness in one high-tech company in Taiwan. METHODS: This study was
      conducted as a quasi-experimental design. Among the 54 subjects enrolled in the
      study, 26 subjects of the volunteers agreed to participate in an aerobic exercise
      program. The control group was comprised of a similar sample of 28 subjects
      working at the same company. Subjects in the exercise group participated in a 12
      week aerobic exercise program, while subjects in the control group did not
      participate. RESULTS: The results of analysis of variance with repeated measures
      of health-related physical fitness showed that the subjects in the exercise group
      had significantly more improvements in abdominal muscle strength and endurance
      than the subjects in the control group. CONCLUSIONS: This study indicated that
      one 12-week aerobic exercise program was effective in improving the abdominal
      muscle strength and endurance of employees of a high-tech company.

PMID- 16642734
TI  - Clinical spectrum of meningococcal infection in infants younger than six months
      of age.
AB  - BACKGROUND: Neisseria meningitidis is one of the most significant bacterial
      infections in children and adolescents. As transplacental antibodies in the
      circulation gradually decline, the prevalence of meningococcal disease among
      young infants is high, and often presents an invasive clinical manifestation. The
      purpose of the study was to investigate the clinical spectrum of meningococcal
      infection in young infants. METHODS: We retrospectively reviewed of the medical
      charts and analyzed the clinical characteristics and outcomes of 10 infants
      younger than 6 months old with meningococcal disease at the Chang Gung Children's
      Hospital from 1994 through 2004. RESULTS: A total of 10 male infants with a mean
      onset age of 2.9 +/- 1.79 months old were enrolled. All patients presented
      initial symptoms of fever and decreased activity. Seizure attack was noted in six
      cases, and only three patients had purpuric or petechial rash. Laboratory
      findings reflected pyogenic infection including elevated C-reactive protein
      (159.1 +/- 108.8 mg/L), pleocytosis (791.11 +/- 660.83/microL), high protein
      levels (190.43 +/- 157.91 g/dl) and hypoglycorrhachia (28 +/- 20.89 mg/dl) in the
      cerebrospinal fluid. Seven cases presented meningitis; among those, N.
      meningitidis was isolated from blood in two cases. Three of the remaining
      patients had meningococcemia. Penicillin was the most common drug of choice;
      cephalosporin was the alternative. Prolonged antimicrobial therapy (range, 14 to
      42 days) was prescribed in six patients complicated with subdural empyema. No
      deaths were documented. During long-term follow up, two patients developed mental
      retardation, and one of those two also had epilepsy. Both of them had lower birth
      body weight, altered initial conscious level, leukocytopenia and subdural empyema
      with encephalomalacia on brain images. One had insufficient therapy and another
      one was infected by a penicillin resistant strain. CONCLUSIONS: Clinicians should
      be aware of meningococcal infection in young infants because the initial
      presentations may be difficult to distinguish from viral syndrome, and may
      rapidly progress to clinical deterioration. Patients with subdural empyema
      required prolonged courses of antimicrobial therapy. Brain images confirmed the
      presence of encephalomalacia which increased the risk of permanent neurologic
      deficit.

PMID- 16642735
TI  - Factors that influence battered women to leave their abusive relationships.
AB  - This study examines factors associated with leaving an abusive relationship,
      including relationship characteristics, external support, and health status of
      the abused subjects. The subjects included 448 Seattle women whose abuse resulted
      in police involvement or filing for a civil protection order against their male
      partner. Women were followed longitudinally for 9 months. Stepwise logistic
      regression analyses assessed factors independently predictive of leave taking.
      Predictors of leaving the abusive relationship were young age, leaving the
      relationship previously, and having a protection order, an abuse-related
      physician visit, and a high score of psychological vulnerability to abuse.
      Seeking but not receiving external support was negatively associated with leave
      taking.

PMID- 16642736
TI  - Child abduction, parents' distress, and social support.
AB  - This study examines how parents of family and nonfamily abducted children cope
      with stress due to the disappearance of their child. The results show that all
      parents experience distress, regardless of whether it was a family or nonfamily
      abduction. Associated with parental distress are factors such as prior family
      stress, age of the child, recovery status of the child, and measures of social
      support. More specifically, helpful support from friends has been found to
      decrease parents' levels of distress, whereas unhelpful support from family and
      attorneys may increase distress. Mothers and fathers responded to event
      circumstances and social support in significantly different ways. The need for
      further research is discussed in the study's conclusions.

PMID- 16642737
TI  - Help-seeking and coping strategies for intimate partner violence in rural and
      urban women.
AB  - Women experiencing intimate partner violence may use a variety of help-seeking
      resources and coping strategies. The purpose of this study was to examine rural
      (n = 378) and urban (n = 379) women's help seeking, coping, and perceptions of
      the helpfulness of resources used in dealing with partner violence. Overall,
      results suggest that women from both areas utilized a variety of help-seeking
      resources and coping strategies in significantly different ways. Urban women used
      more help-seeking resources than rural women. Urban and rural women used
      different types of resources. Rural women perceived the justice system services
      as less helpful than urban women. Coping strategies and help seeking are related,
      with problem-focused coping associated with the use of more formalized help
      seeking resources. Implications for research and practice are discussed.

PMID- 16642738
TI  - Effects of community violence exposure and parental mental health on the
      internalizing problems of urban adolescents.
AB  - Previous research has documented an association between adolescent community
      violence exposure (CVE) and poor psychological functioning. The purpose of this
      study is to delineate the relations of CVE, parental mental health, and
      adolescent PTSD and depression. Participants consisted of 121 pairs of junior
      high and high school students and their parents. Adolescents completed measures
      to assess their history of violence exposure and current psychological
      functioning. Parents completed a demographic questionnaire and measures assessing
      their psychological functioning. Hierarchical regression analyses were conducted,
      and results indicated that, after controlling for demographic variables and
      family violence exposure, parental mental health emerged as a moderating variable
      in the relation between CVE and adolescent-rated PTSD, but not in the association
      between adolescent CVE and depression. Clinical implications of this study and
      directions for future research are discussed.

PMID- 16642739
TI  - Emotional functioning, attachment style, and attributions as predictors of child
      abuse potential in domestic violence victims.
AB  - To explore cognitive and emotional factors that may exacerbate child-abuse
      potential among domestic violence victims, 80 participants reported on their
      depression, hopelessness, anxiety, and anger as well as their attachment style
      and attributional style. Increased emotional difficulties as well as insecure
      attachment styles were significantly positively correlated with child abuse
      potential, although depression and anxiety were the strongest predictors.
      Externalizing blame for the spousal abuse was not associated with abuse risk.
      Women residing in shelters demonstrated significantly greater abuse risk than
      those in transitional housing programs, suggesting that greater temporal
      proximity to the spousal abuse may in part account for the increased abuse
      potential. Depression and hopelessness, however, appeared particularly relevant
      to increased abuse risk in domestic violence victims in the transitional housing
      system. Implications of these findings for working with battered women in terms
      of their emotional functioning and attachment style are discussed.

PMID- 16642740
TI  - Domestic violence cases involving children: effects of an evidence-based
      prosecution approach.
AB  - This article reports findings from the evaluation of a city-county criminal
      prosecution unit for domestic violence involving children. Data from 446 cases
      prosecuted in the first 2 years of the Joint Prosecution Unit (JPU) were compared
      to a matched group of 446 domestic abuse cases prosecuted by both the city and
      county attorneys' offices in the 2 years prior to inception of the JPU. Results
      of the comparisons indicated that fewer cases were declined or dismissed by the
      new unit, and that cases were prosecuted at a significantly more stringent level.
      Multinomial logistic regression analysis indicated that child and weapon factors
      were associated with increased likelihood of a more serious (i.e., felony) plea
      for the new prosecution unit, relative to the comparison group. Results are
      presented in the context of addressing the difficulties inherent in the
      prosecution of domestic abuse and in light of the increasing awareness of the
      detrimental effects of domestic violence on children.

PMID- 16642741
TI  - A comparative study examining associations between women's drug-related lifestyle
      factors and victimization within the family.
AB  - This study explores and compares the interrelationships between lifespan
      childhood and adult partner victimization and the drug lifestyles for 609 women,
      aged 18-65, from a drug-treatment sample, a women's domestic violence shelter
      sample, and community samples matched with the drug-treatment and shelter
      samples. Significant findings indicate that lifespan childhood and adult partner
      victimization were the strongest predictors of women's drug-related lifestyle
      activities. Three proposed hypotheses were supported to suggest that an
      association exists between the respondents' lifespan childhood and partner
      victimization scores and drug-related lifestyle activities scores, with these
      relationships modified by intervening variables, such as age, marital status,
      partner substance use, and parental substance use. Findings also indicate
      significant differences among the four sample groups in terms of victimization
      and drug-related lifestyle factors. Implications, limitations, and areas for
      future research are discussed.

PMID- 16642742
TI  - Intimate partner violence: prevalence and risk factors for men in Cape Town,
      South Africa.
AB  - This study examined the prevalence of and risk factors for intimate partner
      physical violence against women. Interviews were conducted with a sample of 1,378
      men working in Cape Town municipalities. An average of 42.3% (95% CI: 39.6, 44.8)
      reported physical violence against a partner of the last 10 years, and 8.8% (95%
      CI: 7.3, 10.3) reported physical violence in the past year. After adjustment for
      age, occupational group, and race, the factors associated with use of violence
      against partners of the last 10 years were having no post-school training (OR =
      2.10), witnessing parental violence in childhood (OR = 1.87), involvement in
      fights at work (OR = 2.73) and in communities (OR = 1.54), drug use (OR = 1.99),
      problem alcohol use (OR = 1.98), perceiving hitting women to be acceptable (OR =
      4.54), frequent conflict (OR = 2.40), women's alcohol use (OR = 2.25), conflict
      about sex (OR = 2.16), and conflict about his infidelity (OR = 2.81). The study
      shows that ideas supportive of gender inequality and normative use of violence in
      different settings are major underlying factors for men's violence against
      partners.

PMID- 16642743
TI  - Millennium development goal 5: situation analysis.

PMID- 16642744
TI  - Millennium development goal 5: a review of maternal mortality at the Kenyatta
      National Hospital, Nairobi.
AB  - OBJECTIVES: To review if there is a change in the maternal mortality rate at the
      Kenyatta National Hospital since the inception of the Millennium Development Goal
      strategy in 1990, compared to earlier reviews. DESIGN: A retrospective
      descriptive study. SETTING: Kenyatta National Hospital. SUBJECTS: Maternal deaths
      attributed directly to obstetric causes. MAIN OUTCOME MEASURES: Determination of
      maternal mortality rates of all patients admitted to the Kenyatta National
      Hospital Maternity and died after admission up till six weeks of admission. Also
      determine any avoidable causes of the same. RESULTS: During the period under
      review, there were 27,455 deliveries and 253 maternal deaths giving a maternal
      mortality ratio of 921.5 per 100,000 live births. Direct obstetric causes
      accounted for 71% of all maternal deaths with sepsis, haemorrhage, and
      hypertension being the leading causes. Respiratory tract infections associated
      with HIV/ AIDS infection was the prominent indirect cause. 67.5% of deaths
      occurred in women aged between 25 and 35 years and 78.7% were Para 2 or less.
      Evidently there was poor antenatal clinic attendance with only 28.6% having had
      any attendance at all. CONCLUSION: Antenatal clinic attendance needs to be re
      emphasised if an impact is to be realised in curbing maternal mortality; moreover
      there is need for early referrals and encouraging mothers to deliver under
      skilled care.

PMID- 16642745
TI  - Infertility in a community and clinic-based sample of couples in Moshi, Northern
      Tanzania.
AB  - BACKGROUND: Previous research on the aetiology of infertility in sub-Saharan
      Africa was generally clinic based and it is not known whether findings from this
      work are representative of the general population. A better understanding of the
      medical causes of infertility is crucial for reducing the incidence of
      infertility and for improving the clinical management. OBJECTIVE: To determine
      the type and aetiology of infertility in a community and clinic-based sample.
      DESIGN: Couples identified as infertile in a representative cross-sectional
      survey from a community-based sample of 2019 women aged 20-44 years and couples
      seeking care for infertility at a tertiary health facility. SETTING: The
      community-based sample was drawn from Moshi Urban District and the clinic-based
      sample from patients seeking care at Kilimanjaro Christian Medical Centre (KCMC)
      in 2002 and 2003. PARTICIPANTS: Sixty six couples identified as infertile in the
      community-based sample and 112 couples seeking care for infertility. RESULTS: The
      percentage of primary infertility was 37.1% and secondary infertility was 62.9%.
      Female only factor infertility was identified in 65.9% of the couples, male only
      factor in 6.8%, male and female factors in 15.2% and unexplained infertility in
      12.1%. CONCLUSION: The type and aetiology of infertility were the same in the
      community and clinic-based sample suggesting that the couples seeking infertility
      health care were representative of the general infertile population. Tubal factor
      infertility was the commonest cause.

PMID- 16642746
TI  - Contraceptive use among in and out-of school adolescents in rural southwest
      Uganda.
AB  - OBJECTIVE: To compare the level of contraceptive use among in and out-of school
      rural Ugandan adolescents. DESIGN: Cross sectional survey. SETTING: Mbarara
      district. SUBJECTS: Five hundred in-school and 220 out-of school adolescents aged
      15-19 years. MAIN OUTCOME MEASURE: Contraceptive use. RESULTS: Contraceptive
      prevalence was 171 (23.8%), with 99 (19.8%) among in-school and 72 (32.7%) in out
      of school (OR=0.8, 95% CI=0.5-1.3). Of the 286 who had had sexual intercourse,
      171 (59.8%) were current users with 99 (57.9%) in-school and 72 (42.1%) out-of
      school. The predominant method was the male condom with 80 (56.7%) in-school and
      61 (43.3%) out-of-school (p=0.3). Sixty five (67%) of in-school aged 18-19 used
      contraceptives compared to those less than 18 years (OR=0.4, 95% CI=0.2-0.8). The
      out-of school who were urban residents 51(75%) were more likely to use
      contraceptives (OR=0.3, 95% CI=0.1-0.6). Out-of school with secondary education
      37(84.1%) were more likely to use contraceptives (OR=0.2, 95% CI=0.1-0.5). Cost
      was a barrier for contraceptive use among in-school users 37(77.1%) (OR=2.6, 95%
      CI=1.7-5.4). Stigma surrounding their sexual activity was a barrier to out-of
      school 25 (58.1%) (OR=0.4, 95% CI=0.2-0.8). CONCLUSION: Contraceptive use among
      rural sexually active adolescents is low although the prevalence is higher in out
      of school. Reorientation of contraceptive services to make them more accessible
      through strengthening of school health programme and establishment of out-of
      school adolescent health programme are urgently needed.

PMID- 16642747
TI  - Pulmonary tuberculosis in the Central Prison of Douala, Cameroon.
AB  - OBJECTIVE: To determine the prevalence of and factors associated with pulmonary
      tuberculosis (PTB) in an urban prison in sub-Saharan Africa. DESIGN: A cross
      sectional survey. SETTING: The Central Prison of Douala, Cameroon. RESULTS: Two
      thousand four hundred and seventy four (87.4%) out of 2830 inmates underwent
      screening. Twenty seven (1.1%) of the inmates were under treatment for smear
      positive PTB on commencement of the survey while 60 (2.4%) were diagnosed with
      smear and/or culture-positive PTB during the active case finding, resulting in a
      point prevalence of PTB of 3.5%. HIV seroprevalence in inmates without clinical
      signs of PTB was 111/1067 (10.4%) while it amounted to 6/24 (25%) in PTB
      patients. In multiple stepwise regression analysis, a low BMI, a prison stay of <
      or = 12 months, and a history of previous incarceration were positively
      associated with PTB. CONCLUSION: The study results confirm the high prevalence
      rates of PTB in prison populations and underscore the need for urgent preventive
      measures.

PMID- 16642748
TI  - Use and misuse of aspirin in rural Ethiopia.
AB  - OBJECTIVES: To investigate ability to distinguish simple analgesics, to document
      misconceptions about aspirin use, and to identify strategies to diminish
      potentially harmful aspirin use in Ethiopia. DESIGN: Qualitative study (eight
      focus group discussions) used to inform cross-sectional survey. SETTING:
      Butajira, a small town in southern Ethiopia, and surrounding rural areas.
      PARTICIPANTS: Purposively selected informants for focus groups; random sample of
      urban and rural residents for cross-sectional survey. MAIN OUTCOME MEASURES:
      Ability to distinguish aspirin from paracetamol; proportion using aspirin;
      proportion aware of common risks of aspirin. RESULTS: Questionnaires were
      completed by 204 of the 250 residents sampled (82% response). Three-quarters of
      survey participants knew the difference between aspirin and paracetamol. Aspirin
      was used by 7.3% of respondents, and was mainly taken for headache and fever. In
      focus group discussions there was a suggestion that aspirin was considered
      particularly useful for children. There was very low awareness of the risks of
      using aspirin in children (2.5% unprompted, 18.6% prompted) or in people with
      asthma (1% unprompted, 5.9% prompted). Aspirin is cheap and widely available in
      urban and rural areas. CONCLUSION: Awareness of the risks of aspirin use by
      children and in asthma is extremely low in this rural Ethiopian setting.
      Medications are purchased with minimal packaging by a population with low
      literacy. Drug dispensers and vendors must be trained to convey simple verbal
      warnings about aspirin use.

PMID- 16642749
TI  - Pattern and outcome of abdominal injuries at Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVE: To establish the pattern and results of interventions in patients with
      abdominal injuries requiring admission. DESIGN: A descriptive, prospective,
      hospital-based study involving observation of patients from admission to final
      outcome of management as either discharged or deceased. SETTING: Kenyatta
      National Hospital, a tertiary teaching and referral hospital in Nairobi, Kenya,
      from November 2004 to February 2005 in the adult general surgical wards.
      PATIENTS: Eighty consecutive admissions of adult patients with either blunt or
      penetrating abdominal injuries. MAIN OUTCOME MEASURES: Type and cause of injury,
      demographic data, temporal parameters, morbidity and mortality. RESULTS: The 80
      patients had a male to female ratio of 12.3:1, the majority were in the third
      decade of life with a range 15-56 years and mean of 28.2 years. Penetrating to
      blunt abdominal injuries had 2:1 ratio with the leading causes of injury being
      stab wounds, gunshot wounds and road traffic accidents. Blunt abdominal injuries
      had a higher tendency to extra-abdominal injuries. Duration prior to presentation
      to hospital and surgery depended on severity of injury. Modes of management
      varied between attending surgical firms. There was a 20% change in the mode of
      management and a 16.1% rate of negative laparotomy. Penetrating injuries had a
      better interventional outcome. Penetrating abdominal injuries had higher rates of
      complications while the blunt injuries had higher rates of mortality. Overall,
      both the complication and mortality rates were 12.5%. Correlates of mortality
      included delay before surgery, associated injuries, need for blood transfusion,
      admission to intensive care unit and duration prior to admission. Abdominal
      injury patients stayed an average of 6.4 days with the blunt injuries with
      complications staying close to twice as much as their penetrating counterparts.
      CONCLUSION: Abdominal injuries are a predominantly male disease with the majority
      in the third decade of life. As opposed to previous studies, gunshot wounds are
      now a significant cause of abdominal injuries in Kenyatta National Hospital
      (KNH). The rate-of negative laparotomies has come down by 10% over the past 15
      years. The outcome of management depends on the severity and type, of injury
      sustained.

PMID- 16642750
TI  - Haematological, lipid profile and other biochemical parameters in normal and
      hypertensive subjects among the population of the eastern province of Saudi
      Arabia.
AB  - OBJECTIVE: To determine the lipid profile complete blood count and other
      biochemical parameters in normotensive and hypertensive individuals. DESIGN:
      Cross-sectional population-based epidemiological household survey. SETTING:
      Population sample of the Eastern Province of Saudi Arabia. RESULTS: Hypertensive
      individuals had significantly higher mean levels of glucose, Tc, LDL-c, HDL-c,
      triglycerides and HBAIc, compared to normotensive individuals while there were no
      significant difference in the mean levels of Apo AI and Apo B. Within the same
      group there were variations in the levels of certain parameters between male and
      female. While the mean levels of haemoglobin, WBC and platelets were
      significantly higher in the hypertensive group compared to normotensive, there
      were no significant differences between these two groups in the levels of RBC,
      MCV, HCT, MCH and MCHC. However, the mean levels haemoglobin, RBC count and HCT
      were significantly higher in male compared to female within the same group with
      no significant difference in levels of WBC, MCV, MCH and MCHC. Furthermore, the
      mean concentration of platelets was significantly higher in females compared to
      male within the same group. Hypertensive individuals had significantly higher
      serum sodium, chloride and calcium levels but a significantly lower potassium
      level when compared to normotensive with no siginificant differences between male
      and female within the same group. CONCLUSION: The lipid and electrolyte profile
      of hypertensive individuals differ from that of normotensive individuals in this
      population. This study has contributed towards establishing the normal values for
      a number of parameters involved in the aetiology of cardiovascular diseases in
      the population of Eastern province.

PMID- 16642751
TI  - Effect of Helicobacter pylori infection on deep vein thrombosis seen in patients
      with Behcet's disease.
AB  - OBJECTIVE: To investigate the role of homocysteine metabolism due to Helicobacter
      pylori infection on the development of deep vein thrombosis (DVT) in patients
      with Behcet's disease (BD). DESIGN: Prospective clinical study. SETTING: Teaching
      hospital. SUBJECT: Fifty-five patients with BD divided into groups, with DVT and
      without DVT, 19 healthy individuals and 18 patients with coronary artery disease
      (CAD) were enrolled into the study. INTERVENTIONS: Plasma homocysteine and Hp
      seropositivity were determined. RESULTS: There was significant Hp positivity in
      all groups (p > 0.05). Homocysteine levels were not significantly different for
      each group except patients with CAD (p > 0.05). CONCLUSION: There was no
      difference for frequency of Hp infection in all groups. We conclude that Hp does
      not influence DVT seen in BD via homocysteine metabolism, but the methinnin
      loading test would be appropriate for enlighting patients whose fasting plasma
      homocysteine levels are found to be normal.

PMID- 16642752
TI  - The role of neuro-electrophysiological diagnostic tests in clinical medicine.
AB  - OBJECTIVE: To summarise and discuss the role of neuro-electrophysiological
      diagnostic tests in clinical medicine. DATA SOURCES: Published original research
      and reviews to date. STUDY SELECTION: The review was with emphasis on diagnosis
      of peripheral neuropathic and neuromuscular disorders. DATA EXTRACTION AND
      SYNTHESIS: On-line and manual library searches provided information and data on
      which the summaries and discussions were based. Some physicians are not yet aware
      of some of the tests and some may not know their indications. In this article a
      review is made of evoked potential tests, nerve conduction tests and
      electromyography in diagnosis of neurological diseases. An attempt has been made
      to clearly show their indications, and relative importance. CONCLUSION: Studies
      clearly show that neuro-electrophysiological tests are important in neurological
      diagnosis in clinical medicine and are an extension of the physical examination.

PMID- 16642753
TI  - An evidence base for International Health Regulations: quantitative measurement
      of the impacts of epidemic disease on international trade.
AB  - When cholera broke out in Mozambique, Kenya, Tanzania and Uganda in 1997, an
      urgent measure was filed with the Sanitary and Phytosanitary Committee of the
      World Trade Organization, by the European Union, citing the protection of human
      health, to limit imports of fish products. The authors analysed import data on
      specified products over time to quantify the trade impact of this measure. Using
      previous specific trade trends, the authors modelled expected trade flows and
      compared observed imports with expected imports to calculate the potential cost
      of lost trade. The conclusion of this analysis was that the impact of European
      restrictions on fish exports from Mozambique, Kenya, Tanzania and Uganda on the
      economies of these African countries was at least US dollar 332,217,415 for the
      years 1998 to 2002. Insights from such quantitative studies will be important in
      making policy choices under the revised International Health Regulations of the
      World Health Organization and should inform the discussion about the adoption of
      these regulations.

PMID- 16642754
TI  - A review of economic tools for the assessment of animal disease outbreaks.
AB  - This paper demonstrates how currently underutilised economic modelling techniques
      can enrich the analysis of animal disease problems. Increasingly, analyses of
      animal health programmes are expected to address a range of economic and social
      questions. These expectations can be addressed by better integration of
      epidemiological modelling with economic techniques whose application to animal
      health has not been thoroughly discussed in past reviews. This paper describes a
      range of economic models that can be applied in animal health research and
      provides guidance for determining the appropriate method given the issues at
      hand. The complexity of some of these approaches underlines the importance of
      multidisciplinary research and education.

PMID- 16642755
TI  - Enhancing economic models for the analysis of animal disease.
AB  - This paper discusses how economic tools can be targeted and combined to enhance
      their usefulness in analyses of animal disease problems. It briefly reviews the
      most commonly used economic modelling techniques to clarify the applicability of
      specific economic methods to different problems in animal health analysis. The
      paper then reviews applications of these methods in the literature and suggests
      how further research could integrate and improve different economic approaches
      and link epidemiological and economic methods to address a wider range of issues
      at different scales of analysis.

PMID- 16642756
TI  - The use of a web-based interactive geographical information system for the
      surveillance of bluetongue in Italy.
AB  - Since 2000 Italy has experienced five epidemics of bluetongue, an arthropod-borne
      disease that affects primarily sheep and asymptomatically cattle, goats and
      wildlife ruminants. In four years the disease spread through Southern and Central
      Italy, involving 14 Italian regions out of 20. To control the disease, the
      Ministry of Health established a surveillance system that included clinical,
      entomological and serological surveillance elements. The National Reference
      Centre for Veterinary Epidemiology--Istituto Zooprofilattico Sperimentale
      dell'Abruzzo e del Molise 'G. Caporale'--developed a Web-based National
      Information System (NIS) and a Geographical Information System (GIS)to collect
      and manage data from Veterinary Services across Italy. The system was designed to
      gather and spread information in order to support the management of control
      activities and to provide an early warning system. Surveillance data are
      displayed to the user in different ways: reports, tables and interactive maps.

PMID- 16642757
TI  - Surveillance of wildlife as a tool for monitoring rinderpest and peste des petits
      ruminants in West Africa.
AB  - The authors provide a report on the surveillance of rinderpest virus (RPV) and
      peste des petits ruminants virus (PPRV) in the wildlife population in Cote
      d'Ivoire. For this purpose, 266 animals from nine different species, selected
      according to susceptibility and abundance, were captured and sampled from Comoe,
      Marahoue and Lamto Parks. Two hundred and forty seven sera and 214 nasal swabs
      were collected and analysed by competitive enzyme-linked immunosorbent assay
      (cELISA) and reverse-transcriptase polymerase chain reaction (RT-PCR) techniques,
      respectively. Serological data demonstrated that RPV was not circulating within
      the national Parks and estimated the PPR seroprevalence to be less than 1%. The
      analysis of the nasal swabs revealed no cases of RPV infection, but PPRV
      infection was detected in four species, including buffalo. To minimise the cost
      of the study without affecting the sensitivity of the test, samples were pooled
      into different groups and submitted to RT-PCR using nucleoprotein gene specific
      primers. The RT-PCR used in this study, which was derived from the method
      developed by Couacy-Hymann et al. in 2002, was followed by a hybridisation step
      using internal specific probes to confirm the identity of the deoxyribonucleic
      acid product. When used in conjunction with a cELISA this method accurately
      demonstrated the absence of rinderpest viral persistence in Cote-d'Ivoire.

PMID- 16642758
TI  - A study on the epidemiology of brucellosis in Punjab (India) using Survey
      Toolbox.
AB  - A random survey was conducted to study the epidemiology of brucellosis in Punjab
      (India), using the 'Survey Toolbox' sampling software. A two-stage sampling
      procedure was adopted: in the first stage, villages were selected, and in the
      second the selection of animals was made. In all, 52 villages were selected
      randomly from a sampling frame of all the villages of Punjab. The total number of
      animals in these villages was 18,644, out of which 973 animals (approximately 5%)
      belonging to various owners were randomly selected. Serum samples collected from
      the animals were screened for Brucella antibodies by an avidinbiotin enzyme
      linked immunosorbent assay, which showed the apparent overall prevalence of
      brucellosis to be 12.09% (true prevalence, 11.23%). The prevalence varied from a
      low of 0% to a high of 24.3% in various districts. Higher variance (0.08) was
      noted within villages than between different villages (0.03). The prevalence
      rates among buffaloes and cattle were 13.4% and 9.9%, respectively. The
      seroprevalence of brucellosis was found to be significantly higher (chi square =
      24.50, p < 0.001) in animals with a history of abortion (33.87%) than in those
      without such a history (11.63%).

PMID- 16642759
TI  - [Health risks associated with the migration of Atlantic salmon (Salmo salar L.):
      an epidemiological surveillance programme in Northern Spain].
AB  - The authors present the results of an epidemiological surveillance programme
      involving Atlantic salmon (Salmo salar) populations in north-eastern Spain. The
      study investigates the risk factors critical in disease transmission, which
      include the presence of potentially pathogenic micro-organisms, the innate cell
      mediated immune response of the salmon, and the potential interactions between
      the two. Also taken into account are the biological and migratory cycles of these
      salmon populations. The results showed that Aeromonas salmonicida and Saprolegnia
      parasitica were the micro-organisms that played the most important role in the
      transmission of the disease by virtue of their pathological characteristics,
      their occurrence in large numbers, and their capacity to transmit disease. With
      regard to the cell-mediated immune response, the authors observed a wide
      variability between individuals in some cell groups, as well as certain seasonal
      and age differences. These may be factors that predispose the animals to
      infection or to becoming asymptomatic carriers, with the attendant risk of
      transmitting infection in the course of migration. This could be especially
      relevant in the case of salmon infected with A. salmonicida and S. parasitica,
      since it has been observed that such salmon have a decreased number of leucocytes
      compared to non-infected salmon.

PMID- 16642760
TI  - [An epidemiological survey of equine anaplasmosis (Anaplasma phagocytophilum) in
      southern France].
AB  - Anaplasmosis is caused by the bacterium Anaplasma phagocytophilum and transmitted
      by Ixodes spp. ticks. According to some reports the disease can be introduced
      into disease-free zones by migrating birds. The purpose of this study was to
      evaluate the seroprevalence of A. phagocytophilum in horses in the Camargue. Data
      concerning 424 horses were gathered and the sera were tested for A.
      phagocytophilum and for piroplasmoses using an enzyme-linked immunosorbent assay
      and a complement fixation test, respectively. The seroprevalence rates were 11.3
      % for A. phagocytophilum, 64.4 % for Theileria equi and 19.7% for Babesia
      caballi. Stallions were less likely to produce antibodies against A.
      phagocytophilumthan were females or geldings (odds ratio [OR] = 0.3; p = 0.021).
      The presence of swallows increased the risk of infections in stables (OR = 5.18;
      p = 0.011). Spatial analysis showed the existence of groups of infected stables
      along canals and rivers (p = 0.008). These results suggest an emergence of A.
      phagocytophilum in the Camargue.

PMID- 16642761
TI  - An epidemiological study of sheep pox infection in Karnataka State, India.
AB  - Analysis of retrospective quantitative sheep pox epidemiological data from the
      Government Animal Husbandry Department, Karnataka, India, covering 24 years
      revealed significant information on sheep pox. The state has a dense sheep
      population including some valuable breeds. Data revealed the endemicity of the
      disease: there were a considerable number of outbreaks and attacks, high
      mortality and case fatality rates and low immunisation coverage. None of the
      years studied were free from infection. Temporally, the disease was most
      prevalent between November and May. Spatially, the disease was recorded in 19 out
      of 27 districts; in some of these districts sheep pox was highly endemic, in some
      it was endemic at low levels and in the remaining districts outbreaks occurred
      sporadically. Environmental factors influenced disease occurrence. Vaccine
      production met only one tenth of the requirement, and its peak utilisation was in
      the dry season.

PMID- 16642762
TI  - The use of community-based animal health workers to strengthen disease
      surveillance systems in Tanzania.
AB  - An 18 month trial was conducted in three districts of Arusha region, northern
      Tanzania, to assess the use of community-based animal health workers (CAHWs) in
      an official disease surveillance system. Disease reports provided by CAHWs were
      assessed using six indicators for effective disease surveillance, i.e.
      sensitivity, specificity, timeliness, representativeness, simplicity and
      acceptability. To assess sustainability issues and determine the incentives
      required by CAHWs to report disease, three different incentive models were tested
      in the trial. None of the incentive models involved direct payments to CAHWs.
      Before involving CAHWs in disease surveillance in the three trial districts,
      disease case reports as a proportion of cattle population were 0.13%, 0.20% and
      0.12%. During the trial, disease case reports as a proportion of cattle
      population increased to 5.0%, 5.6% and 6.3%. The CAHWs also improved the spatial
      and temporal coverage of the disease surveillance system and provided timely
      reports. During the trial, national-level disease reporting in Tanzania increased
      by 17% owing to the sensitisation and support activities of the Pan African
      Programme for the Control of Epizootics in Tanzania. In Arusha region, disease
      reporting increased by 118%, and 49% of this improvement was attributable to
      increased reporting in the three trial districts. Reporting from these districts
      far exceeded that from any other district in Tanzania. Veterinarians confirmed
      the CAHWs' clinical diagnosis in 88% of the 170 clinical cases examined. The
      increase in disease reporting resulting from CAHW activities was sufficient to
      enable the national epidemiology unit to achieve its target in relation to World
      Organisation for Animal Health (OIE) guidelines. The authors conclude that the
      use of CAHWs should be promoted in the national strategy for disease reporting.
      Additionally, CAHWs must be brought under the control of the Tanzanian veterinary
      authorities, a process that will include appropriate legislative reform.

PMID- 16642763
TI  - Control of an outbreak of highly pathogenic avian influenza, caused by the virus
      sub-type H5N1, in Japan in 2004.
AB  - An outbreak of highly pathogenic avian influenza (HPAI), caused by the virus sub
      type H5N1, occurred at four premises in three prefectures in Japan during January
      and March 2004. As a result, 274,654 poultry died or were slaughtered. This was
      the first outbreak of HPAI in Japan since 1925. (The earlier outbreak was caused
      by H7N7.) The disease was successfully eradicated within three-and-a-half months,
      following an eradication campaign that included depopulating the affected
      premises, implementing movement controls and intensive surveillance. Control
      measures were conducted in accordance with the National Manual of HPAI Control.
      However, during the eradication campaign, some key issues arose, such as delays
      in notification by the affected farmers. As a result of these experiences, the
      relevant laws and HPAI Control Manual have been appropriately revised.

PMID- 16642764
TI  - Studies of the outbreaks of foot and mouth disease in West Bengal, India, between
      1985 and 2002.
AB  - Foot and mouth disease (FMD) is the major disease constraint on international
      trade in livestock and their products. In the state of West Bengal, India, 1,082
      FMD outbreaks were reported in the 18 years from 1985 to 2002. Of the prevalent
      four serotypes, O type FMD virus accounted for the most outbreaks (67%), followed
      by Asia-1 virus type (15%) and A virus type (14%). Outbreaks of the type C FMD
      virus were least prevalent (4%), and no cases have been recorded since 1996. The
      study shows clearly that incidences were highest during the winter months and in
      the alluvial agro-climatic zones. The distribution and density of the FMD
      susceptible population in different districts of the state also played major role
      in disease incidences. Due to the unrestricted movements of animals among
      different cattle markets, the disease was transmitted either by direct contact or
      by aerosols from infected to healthy animals. Cattle suffered most from the
      disease, accounting for about 95% of the cases. The monitoring of the disease
      documented in this study provides information about the endemicity of the disease
      that can help to formulate an effective strategy for an FMD control programme.

PMID- 16642765
TI  - Seroprevalence of bluetongue virus antibodies in sheep and goats in Kerala State,
      India.
AB  - The results presented here record the first confirmation of bluetongue virus
      (BTV) antibody in sheep and goats in Kerala State. A total of 1,010 sera
      collected from the 14 districts within the state were screened for the presence
      of group-specific BTV antibodies by dot enzyme-linked immunosorbent assay (dot
      ELISA). Positive samples were obtained from 12 of the 14 districts. The overall
      BTV antibody prevalence was 5.1 +/- 1.9% (at 95% confidence level) although the
      prevalence levels were consistently higher in organised farms than in the field
      population. Comparative tests carried out using the dot ELISA and competitive
      ELISA (C ELISA) showed a good agreement for all the positive sera. The dot ELISA
      was simple to perform, economic and rapid, and is therefore ideally suited for
      routine screening for BTV antibody at the farm level.

PMID- 16642766
TI  - Salmonellosis in pigmy hogs (Sus salvanius)--a critically endangered species of
      mammal.
AB  - The pigmy hog (Sus salvanius) is the smallest and the rarest wild suid in the
      world. This species is on the verge of extinction and the World Conservation
      Union has rated it among the most endangered of all mammals. This paper reports
      the investigation into an outbreak of salmonellosis among captive pigmy hogs at
      the Research and Breeding Centre of the pigmy hog conservation programme,
      Guwahati, Assam, India. Of 75 pigmy hogs (38 males and 37 females) maintained at
      the Centre, seven (9.3%) died within five days. The causative organism associated
      with the outbreak was identified as Salmonella Typhimurium (syn. S. enterica
      serovar Typhimurium). All the isolates of S. Typhimurium belonged to phage type
      DT193. The isolates harboured multiple plasmids. Five isolates harboured four
      (65.0 MDa, 4.2 MDa, 3.0 MDa, 1.3 MDa), while two isolates carried three plasmids
      (65.0 MDa, 4.2 MDa, 3.0 MDa). All strains showed resistance to amikacin,
      ampicillin, streptomycin and sulfamerazin; five strains were resistant to
      oxytetracycline and trimethoprim. All the strains were sensitive to
      chloramphenicol, ciprofloxacin, enrofloxacin and gentamicin. All seven isolates
      of S. Typhimurium were found to harbour stn, sopB and pefA genes. However, none
      of them was found to carry sefC and sopE genes.

PMID- 16642767
TI  - Observations on the trypanosomosis problem outside the tsetse belts of Sudan.
AB  - Entomological and trypanosomosis surveys were conducted in the Blue Nile area
      between Admazien and Khartoum. The surveys showed the area to be tsetse free. The
      only species of trypanosome found to infect cattle in this study was Trypanosoma
      vivax, which infected some of the local cattle that had no history of entering
      tsetse belts. The prevalence of disease varied with the season. High disease
      prevalence coincided with the periods when tabanid and stomoxy flies were
      abundant. The study showed that the months when biting flies were most numerous
      coincided with trypanosomosis outbreaks, but even minimal numbers of these flies
      may cause the cycle of mechanical transmission to continue in stable enzootic
      conditions.

PMID- 16642768
TI  - Abortion due to Brucella abortus in sheep in Nigeria.
AB  - This paper reports on a sporadic, naturally acquired infection of sheep with
      Brucella abortus on a privately owned farm in Toro near Bauchi, Nigeria. The
      abortions, which occurred in a flock of 28 Yankassa sheep, involved five ewes at
      the third month of gestation. Serum and milk samples from the flock were examined
      for Brucella antibodies by the Rose Bengal plate test, serum agglutination test
      (SAT) and milk ring test (MRT). The proportion shown as positive by SAT was
      14.3%. All the five milk samples examined by MRT were positive. A total of seven
      isolates of Brucella were obtained from three milk samples and four vaginal swabs
      collected from aborting ewes. All isolates were identified and biotyped as B.
      abortus biovar 1. This biovar was also isolated from cattle maintained on the
      farm in association with the sheep. The infection was attributed to the animal
      husbandry practices employed on the farm.

PMID- 16642769
TI  - Selection of foot and mouth disease vaccine strains--a review.
AB  - The choice of the most appropriate strains of foot and mouth disease (FMD) virus
      vaccines to use in FMD control programmes and to store in vaccine antigen
      reserves is based on the matching of representative field isolates from outbreaks
      around the world to available vaccine strains. However, those involved in FMD
      control at a national level do not always give this work a high priority, while
      in countries without effective control of FMD there is little incentive to
      collect samples or to overcome the constraints on submission to international
      reference laboratories. In the short term, specific initiatives for targeted
      collection can provide samples on a periodic basis, but a long-term solution
      requires the development of FMD control measures. This must be underpinned by the
      strengthening of local Veterinary Services and laboratories, and by demand-driven
      provision of sufficient amounts of high-quality vaccine. Difficulties may be
      increased by commercial constraints on disclosure of the strains used for vaccine
      production and on the supply of reagents needed for matching tests. Vaccine
      matching tests are mainly based on in vitro methods - such as virus
      neutralisation, enzyme-linked immunosorbent assay with polyclonal antibodies and
      complement fixation - and are performed in a relatively small number of
      laboratories around the world. In addition to the difficulties of gathering
      representative field and vaccine strains, neither the reagents nor the methods
      used for vaccine matching are fully harmonised. Consequently, there is no strict
      equivalence in the results obtained. Alternative approaches using monoclonal
      antibody panels and/or viral capsid gene sequencing are being developed and could
      complement the currently employed serological tests. However, there is limited in
      vivo cross-protection information, more of which is essential for future
      validation of the vaccine matching methods. In response to the funding and
      leadership deficit for vaccine strain selection, a network of World Organisation
      for Animal Health (OIE) and Food and Agriculture Organization FMD reference
      laboratories has been established; this gives these laboratories the potential to
      strengthen the coordination of their work and reporting and thereby improve
      recommendations on vaccine strain selection.

PMID- 16642770
TI  - Quality assurance/quality control of foot and mouth disease solid phase
      competition enzyme-linked immunosorbent assay--Part I. Quality assurance:
      development of secondary and working standards.
AB  - International movement in animals and animal products has urged organisations
      like the World Organisation for Animal Health (OIE) to draw up guidelines to
      regulate and facilitate trade between Member Countries. However, as the global
      market continues to grow, further standardisation and harmonisation of antibody
      detection assays for infectious diseases are needed, especially regarding the
      development and use of reference materials. For OIE notifiable diseases for which
      primary or international reference standards are available or under development,
      National or Regional Reference Laboratories are encouraged to establish their own
      secondary and/or working standards. This paper describes the development of
      standards for the foot and mouth disease (FMD) solid phase competition enzyme
      linked immunosorbent assay using positive serum obtained from calves vaccinated
      against the FMD virus. The procedure outlined in this manuscript can easily be
      extrapolated to similar serological assays and should lead to further
      international harmonisation of assays and test results.

PMID- 16642771
TI  - Quality assurance/quality control of foot and mouth disease solid phase
      competition enzyme-linked immunosorbent assay--Part II. Quality control:
      comparison of two charting methods to monitor assay performance.
AB  - Diagnostic laboratories are increasingly required to meet stringent quality
      standards, and validated assays are needed to achieve formal accreditation.
      Validation of test methods is often considered to be finalised when the assay
      parameters and characteristics have been established. However, like any process,
      diagnostic assays are subject to random variation resulting in shifts in the mean
      test values. Continuous monitoring of assays using control charts will alert the
      interpreter of changes in performance. For this purpose, several charting methods
      have been developed and implemented. This paper compares the Shewhart and the
      exponentially weighted moving average (EWMA) control charts with respect to the
      day to day monitoring of internal quality control samples for the foot and mouth
      disease solid phase competition enzyme-linked immunosorbent assay. Both chart
      types are equally sensitive to shifts, but the EWMA method seems to provide the
      best balance between false rejection and false acceptance.

PMID- 16642772
TI  - Global detection and identification of Campylobacter fetus subsp. venerealis.
AB  - Bovine genital campylobacteriosis caused by Campylobacter fetus subsp. venerealis
      (Cfv) is a genital infection that threatens the cattle industry. Detection and
      identification of Cfv are key factors in control programmes. Trade regulations
      should be based on scientifically and internationally accepted methods of
      detection and identification of Cfv. Such methods are described in the World
      Organisation for Animal Health (OIE) Manual of Diagnostic Tests and Vaccines for
      Terrestrial Animals. A study was conducted to determine which methods are in use
      in OIE Member Countries and to get an overview of new or improved tests. A
      questionnaire was sent to OIE Member Countries, and 26 out of 166 were returned.
      Globally, a diversity of methods for the detection and identification of Cfv are
      in use. The authors conclude that there is a lack of harmonisation that may have
      consequences for the description of the health status of countries and may lead
      to disputes with respect to trade regulations.

PMID- 16642773
TI  - A review of tests available for use in the diagnosis of tuberculosis in non
      bovine species.
AB  - Bovine tuberculosis is an important disease that has impacts on regional and
      international trade. The disease can affect both social and economic stability
      and have a deleterious affect on species diversity. The intradermal tuberculin
      test has been in use for almost a century and, despite the technological advances
      of the last two decades, is still the only prescribed test for the diagnosis of
      tuberculosis in cattle. Many other species of animal, including humans, can be
      infected with Mycobacterium bovis. This paper reviews the various tests that have
      been used by researchers for detecting infection with M. bovis in a variety of
      animal species, and attempts to prioritise or comment on the importance of having
      appropriately validated diagnostics for the different species. The difficulties
      of test validation using small numbers of animals, especially when tuberculosis
      occurs in only a few instances or the species of animal affected is rare and/or
      valuable, are discussed.

PMID- 16642774
TI  - Molecular typing of Mycobacterium avium subspecies paratuberculosis strains from
      different hosts and regions.
AB  - The IS1311 polymerase chain reaction-restriction endonuclease analysis was used
      to detect genetic differences among 38 Mycobacterium avium subsp.
      paratuberculosis (Map) isolates from cattle, sheep, goats and bison from distinct
      regions of Spain, India and the United States of America (USA). In Spain, all
      eight bovine isolates, three out of six caprine isolates and one of ten ovine
      isolates were of the C type, while the other nine ovine isolates and three
      caprine isolates were of the S type. In India, all five ovine isolates and six
      caprine isolates were of the B type, and so were all three isolates from bison
      (Bison bison) from the USA. These results show that there are genetic differences
      between Map isolates related to geographic and host factors that have a potential
      use in the epidemiological tracing of new paratuberculosis isolates.

PMID- 16642775
TI  - Use of the polymerase chain reaction for diagnosing bovine tuberculosis in
      Panama.
AB  - In addition to causing large losses to the cattle industry, Mycobacterium bovis,
      the causative agent for bovine tuberculosis, is a serious public health issue
      because it can potentially infect humans. Diagnosis based on isolation and
      identification of the bacillus is tedious and may take weeks. The diagnosis of M.
      bovis by polymerase chain reaction (PCR), using species-specific primers, is
      fast, highly sensitive and of great value in epidemiological studies. In this
      study, deoxyribonucleic acid (DNA) was extracted from 60 nasal mucus samples
      collected from three different farms, all located in an area where M. bovis is
      endemic. Two farms tested negative for an antibody response to the M.
      tuberculosis purified protein derivative (PPD) antigen, whereas the other farm
      gave a positive result. The amplified fragment of DNA was 460 base pairs with a
      sequence similar to that previously reported. Only 5% of the samples from the
      third farm tested positive for the presence of antibodies against PPD, whereas
      65% of samples (from all three farms) gave a positive result when PCR was used.
      Thus, the authors suggest the use of the PCR species-specific primers test to
      support the programme against bovine tuberculosis in Panama.

PMID- 16642776
TI  - Herd sensitivity in relation to test sensitivity in swine vesicular disease
      serological tests.
AB  - After the swine vesicular disease (SVD) outbreaks in 1992 in the Netherlands a
      national monitoring programme was initiated, testing 12 samples from every pig
      farm three times per year. In this monitoring a slightly higher cut-off was used
      than the cut-off agreed on within the European community. The author has analysed
      the effect of this higher cut-off on the percentage of false positive and false
      negative results, using information on SVD antibody titres in sera obtained from
      the monitoring programme and the outbreaks in 1992 and 1994. The number of false
      positive results was reduced by 63% when using the higher cut-off. On average the
      test sensitivity was reduced from 100% to 88%, resulting in a change of the
      average herd sensitivity from 91.7% to 91.5%, when testing 12 samples per farm.
      When three samples per farm were tested, the average herd sensitivity changed
      from 64.9% to 62.9%. The results further indicate that, in contrast to what is
      generally presumed, there is a relationship between test sensitivity and the
      prevalence of infection. The results clearly show that sample size is far more
      important in obtaining a high herd sensitivity than achieving a high test
      sensitivity.

PMID- 16642777
TI  - Detection of bovine herpesvirus-1 infection in breeding bull semen by virus
      isolation and polymerase chain reaction.
AB  - Serum samples from 51 apparently healthy breeding bulls were screened for bovine
      herpesvirus-1 (BHV-1) antibodies using an avidin-biotin enzyme-linked
      immunosorbent assay, revealing a sero-positive prevalence rate of 45.09%. Semen
      samples were then collected from 12 of the sero-positive and 12 of the sero
      negative bulls and tested for BHV-1 antigen using both a virus isolation assay
      and a polymerase chain reaction (PCR) assay; PCR was applied to detect BHV-1
      deoxyribonucleic acid by using primers selected from the relatively conserved
      sequence of the gl glycoprotein gene to amplify a 468 base pair fragment. The PCR
      amplified products were confirmed as BHV-1 by restriction enzyme, Dde 1, which
      produced fragments of predictable sizes, namely 340 and 128 base pairs. Positive
      virus isolation test results, confirmed by virus neutralisation, found BHV-1
      antigen in the semen of five sero-positive and six sero-negative bulls. In
      comparison, positive PCR results found BHV-1 genome in the semen of six sero
      positive and eight sero-negative bulls. From the 24 semen samples tested, 14 were
      shown to be positive by PCR and 11 by virus isolation. The sensitivity and
      specificity of virus isolation were 57.14% and 70% respectively, and were
      significantly lower than PCR. In the semen samples taken from sero-negative
      bulls, BHV-1 was detected more often by PCR methods than by virus-isolation,
      suggesting that PCR is a more sensitive method for BHV-1 screening in bulls.

PMID- 16642778
TI  - The translation into Spanish of the OIE Manual of diagnostic tests and vaccines
      for terrestrial animals (mammals, birds and bees): problems, solutions and
      conclusions.
AB  - In order to carry out the translation into Spanish of the Manual of diagnostic
      tests and vaccines for terrestrial animals (mammals, birds and bees) ensuring
      full scientific and linguistic accuracy, its authors relied on coordination
      between three types of experts: linguistic, translational and veterinary. In this
      paper the planning, execution and quality control of such work, which was
      undertaken with the support and guarantee of the World Organisation for Animal
      Health (OIE), is reported. In the conclusions the authors describe what they view
      as necessary guidelines for the OIE to apply in the future regarding its
      linguistic policy. The working methodology reported in connection with the
      translation of the Terrestrial Manual into Spanish will be useful for the
      translation of the Terrestrial Manual or other texts into languages other than
      Spanish, whether or not they are among the official languages of the OIE.

PMID- 16642779
TI  - Tests of Olyset nets by bioassay and in experimental huts.
AB  - BACKGROUND: Olyset nets are a type of long-lasting insecticidal net made of
      polyethylene fibre with permethrin incorporated into it and with a 4 mm mesh
      size. BIOASSAYS: Olyset netting was wrapped around a wire frame and the
      mosquitoes were released inside for bioassays. There was significantly faster
      knockdown and higher percent mortality than bioassays with the netting attached
      to a WHO cone with a piece of cardboard on the other side of the net to prevent
      escapes through the large mesh. It is suggested that with the latter method some
      mosquitoes place their tarsae through the mesh on to the cardboard, thus avoiding
      insecticide contact. TRIALS IN EXPERIMENTAL HUTS: Four mm mesh nets were compared
      with conventional 1.5 mm mesh nets treated with permethrin. In further trials in
      huts Olyset nets which were either unwashed or five times washed, with or without
      subsequent heating, and a Olyset net which had been in domestic use for four
      years or a new Olyset net were compared with a net treated with bifenthrin.
      RESULTS & CONCLUSION: In all cases Anopheles biting on sleepers under the nets
      was reduced and Anopheles mortality was increased by the use of the insecticidal
      nets. No significant impact of washing or heating was detected and an Olyset net
      was as good as new after four years use, but did not cause as much mosquito
      mortality as bifenthrin treated nets.

PMID- 16642780
TI  - Larval habitats and species composition of mosquitoes in Darjeeling Himalayas,
      India.
AB  - BACKGROUND & OBJECTIVES: A preliminary survey of larval mosquito habitats and
      temporal variation in mosquito diversity in the hill town of Darjeeling, India
      was made during 2003, for a qualitative and quantitative assessment of mosquito
      distribution. METHODS: The possible larval habitats of mosquitoes were surveyed
      and the species diversity in the sites positive for mosquito larvae was noted. Bi
      weekly sampling from a particular habitat was carried out to reveal the temporal
      variation in mosquito species. RESULTS: A good number of lentic aquatic habitats
      were found to be hosting mosquito immatures, though difference in the physical
      and biological features of these habitats was prominent. Altogether, immatures of
      six mosquito species, belonging to four genera--Aedes, Armigeres, Culex and
      Toxorhynchites were noted with significant difference in temporal variation in
      their relative and absolute numbers. A positive correlation (r = + 0.707) was
      found between population of the prey mosquito immatures and the population of
      immatures of Tx. splendens. The species diversity index (H') for the mosquitoes
      remained between 0.87 and 1.53. The evenness components ranged between 54.03 and
      95.03% and differed significantly. INTERPRETATION & CONCLUSION: In the present
      study, the aquatic bodies could be categorised into six types depending on the
      size and structural complexity that may account for the observed variation in the
      species composition of the larval habitats. In addition to this, other factors
      like temperature, rainfall and other related climatic attributes may be
      responsible for the observed species variation, which needs to be confirmed
      through further studies.

PMID- 16642781
TI  - Behavioural biting preference of Culex quinquefasciatus in human host in Lagos
      metropolis Nigeria.
AB  - BACKGROUND & OBJECTIVES: Olfactory cues play an important role in the attraction
      of major disease vectors towards their host. Hence we intend to investigate the
      contribution of selected parts of the human host on the behavioural biting
      preference of Culex quinquefasciatus. METHODS: Two volunteers were trained to
      collect host seeking female mosquitoes landing to feed on different parts of the
      lower limbs. The Cx. quinquefasciatus were collected in paper cups with the aid
      of a flash-light and aspirator. Each paper cup was labeled to represent the
      selected parts where the mosquitoes were collected. RESULTS: The composition of
      Cx. quinquefasciatus from the total mosquitoes collected showed that Cx.
      quinquefasciatus was more predominant (90%) over other species present. The
      average minimum and maximum atmospheric temperature recorded during the night
      catches were 27 and 29.5 degrees C while the average relative humidity range was
      78-81.6%. The behavioural biting preference results obtained showed that the
      density of Cx. quinquefasciatus mosquitoes preferring the foot region (298) was
      significantly higher (p > 0.05) when compared with other different parts of the
      human host such as the ankle, calf and the thigh. INTERPRETATION & CONCLUSION:
      The study indicates that the foot region of the human host has a stronger
      influence in orientating mosquitoes towards the human host. Hence, the
      exploitation of the characteristic human odour will add to the existing vector
      control strategies.

PMID- 16642782
TI  - Climatic variables and malaria incidence in Dehradun, Uttaranchal, India.
AB  - BACKGROUND & OBJECTIVES: Mosquito-borne diseases particularly malaria and
      Japanese encephalitis (JE) are becoming most dreaded health problems in Dehradun
      district. Keeping in view that the climatic factors particularly temperature and
      rainfall may alter the distribution of vector species--increasing or decreasing
      the ranges, depending on weather conditions that are favourable or unfavourable
      for mosquito breeding, it is aimed to find out the effect of climatic factors on
      malaria incidence with particular emphasis to capture the essential events as a
      result of climatic variability. METHODS: Mosquito sampling and identification was
      done using WHO entomological methods and follow-up of recognised keys and
      catalogues. Data on malaria incidence and meteorological information were
      gathered in a collaborative study with the District Malaria Office, and the
      Forest Research Institute, Dehradun respectively. Pearson's correlation analysis
      was applied for establishing relationship between climate variables and malaria
      transmission. RESULTS: Higher positive correlation of association was found
      between monthly parasite incidence and climatic variables (temperature, rainfall
      and humidity). However, highest significant correlation was found between
      rainfall and malaria incidence (r = 0.718, p < 0.0001) when the data were
      staggered to allow a lag of one-month. INTERPRETATION & CONCLUSION: Climatic
      variables that predict the presence or absence of malaria are likely to be the
      best suited for forecasting the distribution of this disease at the edges of its
      range.

PMID- 16642783
TI  - A study of clinical profile of malaria in a tertiary referral centre in South
      Canara.
AB  - BACKGROUND & OBJECTIVES: The incidence of malaria is on the raise in South Canara
      district of Karnataka in the recent years and there is not much information on
      malaria from this region. This study was undertaken to analyse and introspect the
      presentation of this disease in a tertiary referral centre. METHODS: This
      retrospective case analysis was done on patients over the age group of 15 yr
      admitted with diagnosis of malaria to the Medical Department in this tertiary
      health institution situated in South Canara. The outpatient and inpatient records
      from September 2002 to August 2004 were retrieved and scrutinised using a
      prepared case sheet performa on the basis of patient's demographic profile,
      clinical findings, investigations, treatment and complications. RESULTS: A total
      of 314 patients were diagnosed and treated for malaria, of them 124 were treated
      as outpatients and 190 cases were managed as inpatients. Males (81%) outnumbered
      females (19%) and many were within the age group of 21-30 yr. The incidence of
      malaria increased from the month of June onwards coinciding the monsoon season.
      Plasmodium vivax was the major parasite type (52.54%), followed by P. falciparum
      (33.75%), mixed malarial infection (13.69%) and most of them received combination
      therapy. Hepatopathy was the most common complication and all the deaths were due
      to cerebral malaria. INTERPRETATION & CONCLUSION: Malaria is responsible for
      major health concern in this region, particularly in rainy season and is found to
      affect comparatively the younger adult population. P. vivax was the major
      parasite type causing malaria and most of the complications were due to P.
      falciparum.

PMID- 16642784
TI  - Susceptibility status of Anopheles dthali and An. fluviatilis to commonly used
      larvicides in an endemic focus of malaria, southern Iran.

PMID- 16642785
TI  - Susceptibility status of some culicine mosquitoes to insecticides in Rajahmundry
      town of Andhra Pradesh, India.

PMID- 16642786
TI  - Testosterone induces neuroprotection from oxidative stress. Effects on catalase
      activity and 3-nitro-L-tyrosine incorporation into alpha-tubulin in a mouse
      neuroblastoma cell line.
AB  - 3-nitro-L-tyrosine is formed by nitric oxide following different pathways such as
      NADPH oxidase, xanthine oxidase or glutamate NMDA receptor activation and is
      involved in the pathology of different neurological disorders. Unlike estradiol,
      a neuroprotective role of androgens against oxidative cell injury has not been
      fully investigated. This work targets the possible effects of testosterone on
      neuroblastoma cells exposed to 3-nitro-L-tyrosine. C1300 mouse undifferentiated
      neuroblastoma cells exposed to 3-nitro-L-tyrosine were cultured in the presence
      of testosterone. Morphological examination, proliferation and nuclear viability
      assays were performed. The expression of tyrosinated alpha-tubulin and
      incorporation of 3-nitro-L-tyrosine into protein were also estimated. Cells
      exposed to 3-nitro-L-tyrosine showed globular shape, reduced cytoplasmic
      processes and growth inhibition in comparison with controls. When testosterone
      was added to the medium, these changes were not evident. In addition,
      testosterone induced an upregulation of tyrosinated alpha-tubulin, a marker of
      neuronal plasticity, and a decrease in 3-nitro-L-tyrosine incorporation into
      tubulin. Our results suggest that testosterone exposure can diminish 3-nitro-L
      tyrosine toxic effects on the morphology and growth rate of neuroblastoma cells.
      The upregulation of tyrosinated alpha-tubulin in testosterone-exposed cells would
      be consistent with concurrent plasticity events. Failure in alpha-tubulin
      nitration detected in cells exposed to both 3-nitro-L-tyrosine and testosterone,
      may support the idea that testosterone interferes with 3-nitro-L-tyrosine protein
      incorporation. Moreover, testosterone-induced neuroprotection likely entails a
      linkage with the androgen receptor as is suggested by the flutamide-induced
      inhibition of the hormone activity. Finally, the neuroprotective effects of
      testosterone in neuroblastoma cells could deal with the cellular antioxidant
      defence system, as shown by testosterone-induced increase in catalase activity.

PMID- 16642787
TI  - Feedback hypothesis and the effects of altered gravity on formation and function
      of gravireceptors of mollusks and fish.
AB  - Popular hypothesis based on the idea of simple feedback mechanism that correlates
      gravity level and weight of test mass cannot explain the variety of the effects
      of altered gravity on development and function of gravireceptors. The reaction of
      organisms to the change of gravity depends on the gravisensitivity of the
      physical and chemical processes corresponding to specific phases of development
      and may have no relation to any feedback mechanisms of compensation of altered
      weight of the test mass. The present work analyzes the hypothesis of feedback and
      shows the ambiguity of possible effects of the altered gravity on formation and
      function of gravireceptors basing on the data from mollusks and fish.

PMID- 16642788
TI  - Monophasic and biphasic relaxation during motor unit tetanic contractions of
      variable fusion degree.
AB  - The phenomenon of transition of the monophasic relaxation into biphasic course in
      the unfused tetanic contractions was studied on functionally isolated motor units
      of the rat medial gastrocnemius muscle. The sample consisted of 16 FF, 16 FR and
      10 S MUs which were stimulated with the same, digitally controlled patterns. The
      new parameter--QRT/HRT ratio, was introduced as a convenient tool for the
      classification of the relaxation into monophasic or biphasic. Analysis of tetani
      evoked at increasing stimulation frequencies revealed similar relationships
      between the tetanic fusion degree and the shape of relaxation for all three types
      of motor units investigated. In each MU, the QRT/HRT ratio fell into two distinct
      ranges related to either monophasic (lower values) or biphasic (higher values)
      relaxation. The relationship was also found between the shape of relaxation and
      degree of tetanic fusion--the biphasic course appeared for better fused tetani
      when fusion index was over the mean of 0.8. Mechanisms of development of the
      biphasic relaxation were discussed with respect to importance of this parameter
      in force development and summation of successive contractions into tetanus.
      Moreover, it was pointed out that adequacy of mathematical modeling of motor unit
      contractions should benefit from the precise analysis of the mono- or biphasic
      course of relaxation.

PMID- 16642789
TI  - Hypergravity susceptibility of ventral root activity during fictive swimming in
      tadpoles (Xenopus laevis).
AB  - 1. Fictive swimming is an experimental model to study early motor development. As
      vestibular activity also affects the development of spinal motor projections, the
      present study focused on the question whether in Xenopus laevis tadpoles, the
      rhythmic activity of spinal ventral roots (VR) during fictive swimming revealed
      age-dependent modifications after hypergravity exposure. In addition,
      developmental characteristics for various features of fictive swimming between
      stages 37/38 and 47 were determined. Parameters of interest were duration of
      fictive swimming episodes, burst duration, burst frequency (i.e., cycle length),
      and rostrocaudal delay. 2. Ventral root recordings were performed between
      developmental stage 37/38, which is directly after hatching and stage 47 when the
      hind limb buds appear. The location of recording electrodes extended from myotome
      4 to 17. 3. Hypergravity exposure by 3 g-centrifugation lasted 9 to 11 days. It
      started when embryos had just terminated gastrulation (stage 11/19-group), when
      first rhythmical activity in the ventral roots appeared (stage 24/27-group), and
      immediately after hatching (stage 37/41-group). Ventral root recordings were
      taken for 8 days after termination of 3 g-exposure. 4. Between stage 37/38
      (hatching) and stage 47 (hind limb bud stage) burst duration, cycle length and
      rostrocaudal delay recorded between the 10th and 14th postotic myotome increased
      while episode duration decreased significantly. In tadpoles between stage 37 and
      43, the rostrocaudal delay in the proximal tail part was as long as in older
      tadpoles while in caudal tail parts, it was shorter. During this period of
      development, there was also an age-dependent progression of burst extension in
      the proximal tail area that could not be observed between the 10th and 14th
      myotome. 6. After termination of the 3 g-exposure, the mean burst duration of VR
      activity increased significantly (p < 0.01) when 3 g-exposure started shortly
      after gastrulation but not when it started thereafter. Other parameters for VR
      activity such as cycle length, rostrocaudal delay and episode duration were not
      affected by this level of hypergravity. 7. It is postulated that (i) functional
      separation of subunits responsible for intersegmental motor coordination starts
      shortly after hatching of young tadpoles; and that (ii) gravity exerts a trophic
      influence on the development of the vestibulospinal system during different
      periods of embryonic development leading to the formation of more rigid neuronal
      networks earlier in the spinal than in the ocular projections.

PMID- 16642790
TI  - Synaptically-silent immature neurons show gaba and glutamate receptor-mediated
      currents in adult rat dentate gyrus.
AB  - The fate of adult-generated neurons in dentate gyrus is mainly determined early,
      before they receive synapses. In developing brain, classical neurotransmitters
      such as GABA and glutamate exert trophic effects before synaptogenesis. In order
      for this to occur in adult brain as well, immature non-contacted cells must
      express functional receptors to GABA and glutamate. In this investigation, patch
      clamp recordings were used in adult rat dentate gyrus slices to assess the
      presence and analyze the characteristics of GABA- and glutamate-evoked currents
      in highly immature, synaptically-silent granule cells. Whole-cell patch-clamp
      recordings showed that all the analyzed cells responded to puff application of
      GABA and most of them responded to glutamate. Currents evoked by GABA were
      mediated exclusively by GABAA receptors and those elicited by glutamate were
      mediated by NMDA and AMPA/Kainate receptors. GABAA receptor-mediated currents
      were reduced by furosemide, which suggests that synaptically-silent immature
      neurons express high-affinity, alpha4-subunit-containing GABAA receptors.
      Gramicidin-perforated-patch recordings showed that GABAA receptor-mediated
      currents exerted a depolarizing effect due to high intracellular chloride
      concentration. Synaptically-silent immature cells shared morphological and
      electrophysiological properties with GFP-expressing, 7-day-old adult-generated
      granule layer cells, indicating that they could be in the first week of life, the
      period of maximal newborn cell death. Moreover, the presence of functional GABA
      and glutamate receptors was confirmed in these GFP-expressing cells. Present
      findings are mostly consistent with previous data obtained in female mice
      undergoing spontaneous activity and in transgenic mice, except for some
      inconsistencies about the presence of functional glutamatergic receptors. We
      speculate that adult-generated, non-contacted granule cells may be able to sense
      activity-related variations of GABA and glutamate extracellular levels. This
      condition is necessary, even if not sufficient, for these neurotransmitters to
      have a direct role in addressing cell survival.

PMID- 16642791
TI  - Using digital radiography to increase practice productivity.

PMID- 16642792
TI  - Management of excessive gingival display following adult orthodontic treatment: a
      case report.
AB  - A common cause for the condition described as excessive gingival display is the
      phenomenon known as altered passive eruption, a coronally situated gingival
      complex that failed to recede normally during eruption of an otherwise healthy
      and normal dentition. Orthodontic movement in such conditions may set the stage
      for additional coronal growth of hyperplastic gingival complex. The objective of
      this article is to describe, through a detailed case presentation, the surgical
      methods used to achieve healthy and aesthetic gingival contours in such
      conditions.

PMID- 16642793
TI  - Color stability of provisional restorations.

PMID- 16642794
TI  - Metal-composite copings in the aesthetic restoration of the severely compromised
      patient.
AB  - Aesthetic enhancement of the smile can be as simple as performing tooth whitening
      or as involved as a full-mouth reconstruction. In instances where porcelain
      veneers are contraindicated, when subgingival margin placement is required, or
      when it is necessary to conceal dark substructures or provide occlusal stability,
      metal-ceramic crowns may be required. This presentation highlights the properties
      of a metal-composite coping and demonstrates its application in a full mouth
      reconstruction used by the author to achieve the desired functional and aesthetic
      outcome.

PMID- 16642795
TI  - Aesthetic rehabilitation and functional periodontal stabilization using metal
      ceramic restorations.

PMID- 16642796
TI  - Intracoronal restorations--part II: indirect procedures.

PMID- 16642797
TI  - Hurricane Katrina from a faculty perspective.

PMID- 16642798
TI  - The new partnership in the aesthetic (r)evolution.

PMID- 16642799
TI  - Creating translucent edge effects and maverick internal tints using microhybrid
      resin.
AB  - Today's composite resins possess optical and physical characteristics that have
      expanded their clinical indications. The successful and predictable application
      of these materials depends on the practitioner's understanding of their material
      properties as well as the clinical requirements involved in their delivery;
      identifying the characteristics of the natural tooth is also important. This
      presentation reviews contemporary resin materials and demonstrates simple and
      repeatable guidelines for margin and material placement that improve the
      clinician's ability to implement microhybrid resins in daily practice.

PMID- 16642800
TI  - Dual-probe laser interferometer for structural health monitoring.
AB  - In this note we present the development of a dual-probe laser interferometer that
      uses the filtering properties of a polarized beamsplitter to enable two
      independent (uncoupled) detection probes. The robustness of this system is
      demonstrated by making broadband, noncontact, high fidelity measurements of Lamb
      waves in an aluminum plate.

PMID- 16642801
TI  - Measuring flow resistivity of porous materials at low frequencies range via
      acoustic transmitted waves.
AB  - An acoustic transmissivity method is proposed for measuring flow resistivity of
      porous materials having rigid frame. Flow resistivity of porous material is
      defined as the ratio between the pressure difference across a sample and the
      velocity of flow of air through that sample per unit cube. The proposed method is
      based on a temporal model of the direct and inverse scattering problem for the
      diffusion of transient low-frequency waves in a homogeneous isotropic slab of
      porous material having a rigid frame. The transmission scattering operator for a
      slab of porous material is derived from the response of the medium to an incident
      acoustic pulse. The flow resistivity is determined from the solution of the
      inverse problem. The minimization between experiment and theory is made in the
      time domain. Tests are performed using industrial plastic foams. Experimental and
      numerical results, and prospects are discussed.

PMID- 16642802
TI  - Quantitative measurements of acoustic emissions from cavitation at the surface of
      a stone in response to a lithotripter shock wave.
AB  - Measurements are presented of acoustic emissions from cavitation collapses on the
      surface of a synthetic kidney stone in response to shock waves (SWs) from an
      electrohydraulic lithotripter. A fiber optic probe hydrophone was used for
      pressure measurements, and passive cavitation detection was used to identify
      acoustic emissions from bubble collapse. At a lithotripter charging voltage of 20
      kV, the focused SW incident on the stone surface resulted in a peak pressure of
      43 +/- 6 MPa compared to 23 +/- 4 MPa in the free field. The focused SW incident
      upon the stone appeared to be enhanced due to the acoustic emissions from the
      forced cavitation collapse of the preexisting bubbles. The peak pressure of the
      acoustic emission from a bubble collapse was 34 +/- 15 MPa, that is, the same
      magnitude as the SWs incident on the stone. These data indicate that stresses
      induced by focused SWs and cavitation collapses are similar in magnitude thus
      likely play a similar role in stone fragmentation.

PMID- 16642803
TI  - A theoretical model to predict the low-frequency sound absorption of a helmholtz
      resonator array.
AB  - A theoretical method based on mutual radiation impedance is proposed to compute
      the sound absorption performance of a Helmholtz resonator array in the low
      frequency range. Any configuration of resonator arrangement can be allowed in the
      method, while all the resonators may or may not be identical. Comparisons of the
      theoretical predictions with those done by the past studies or experiments show
      that the present method can accurately predict the absorption performance in more
      general cases.

PMID- 16642804
TI  - Automated pure-tone threshold estimations from extrapolated distortion product
      otoacoustic emission (DPOAE) input/output functions.
AB  - A promising approach to the prediction of pure-tone thresholds through the
      estimation of DPOAE thresholds by input/output functions was recently published
      by Boege and Janssen [J. Acoust. Soc. Am. 111, 1810-1818 (2002)]. On the basis of
      their results, a device that enables automated measurements of these thresholds
      was recently developed. The purpose of the current study was to evaluate the
      reliability of this instrument for the objective assessment of hearing loss in
      101 ears with either normal hearing or with cochlear hearing loss of up to 50 dB
      HL. The median difference between pure-tone hearing and DPOAE thresholds was
      approximately 2 dB. For individual subjects, however, DPOAE thresholds differed
      from pure-tone thresholds by up to 40 dB. We find, therefore, that the clinical
      benefits of this method are probably limited.

PMID- 16642805
TI  - Cochlear compression wave: an implication of the Allen-Fahey experiment.
AB  - In order to measure the gain of the cochlear amplifier, de Boer and co-workers
      recently extended the Allen-Fahey experiment by measuring otoacoustic emissions
      and basilar membrane vibration [J. Acoust. Soc. Am. 117, 1260-1266 (2005)].
      Although this new experiment overcame the limitation of the original Allen-Fahey
      experiment for using a low-frequency ratio, it confirmed the previous finding
      that there is no detectable cochlear amplification. This result was attributed to
      destructive interference of the otoacoustic emission over its generation site.
      The present letter provides an alternative interpretation of the results of the
      Allen-Fahey experiment based on the cochlear fluid compression-wave theory.

PMID- 16642806
TI  - Loudness of brief tones measured by magnitude estimation and loudness matching.
AB  - McFadden [J. Acoust. Soc. Am. 57, 702-704 (1975)] questioned the accuracy and
      reliability of magnitude estimation for measuring loudness of tones that vary
      both in duration and level, whereas Stevens and Hall [Percept. Psychophys. 1, 319
      327 (1966)] reported reasonable group data. To gain insight into this
      discrepancy, the present study compares loudness measures for 5- and 200-ms tones
      using magnitude estimation and equal-loudness matches from the same listeners.
      Results indicate that both procedures provide rapid and accurate assessments of
      group loudness functions for brief tones, but may not be reliable enough to
      reveal specific characteristics of loudness in individual listeners.

PMID- 16642807
TI  - Auditory temporal resolution in normal-hearing preschool children revealed by
      word recognition in continuous and interrupted noise.
AB  - The purpose of this study was to examine temporal resolution in normal-hearing
      preschool children. Word recognition was evaluated in quiet and in spectrally
      identical continuous and interrupted noise at signal-to-noise ratios (S/Ns) of
      10, 0, and -10 dB. Sixteen children 4 to 5 years of age and eight adults
      participated. Performance decreased with decreasing S/N. At poorer S/Ns,
      participants demonstrated superior performance or a release from masking in the
      interrupted noise. Adults performed better than children, yet the release from
      masking was equivalent. Collectively these findings are consistent with the
      notion that preschool children suffer from poorer processing efficiency rather
      than temporal resolution per se.

PMID- 16642808
TI  - Perceptual learning in speech: stability over time.
AB  - Perceptual representations of phonemes are flexible and adapt rapidly to
      accommodate idiosyncratic articulation in the speech of a particular talker. This
      letter addresses whether such adjustments remain stable over time and under
      exposure to other talkers. During exposure to a story, listeners learned to
      interpret an ambiguous sound as [f] or [s]. Perceptual adjustments measured after
      12 h were as robust as those measured immediately after learning. Equivalent
      effects were found when listeners heard speech from other talkers in the 12 h
      interval, and when they had the opportunity to consolidate learning during sleep.

PMID- 16642809
TI  - The method of waveform images for finite waveguides with resistive terminations
      subject to arbitrary initial conditions.
AB  - Reflection at normal incidence of a plane wave can be described by imaging the
      incident wave profile on the opposite side of the boundary. This concept has been
      introduced in a few texts, but only for nondissipative conditions. In this paper
      the procedure to describe a purely resistive boundary is generalized, and then
      the concept is extended to describe the transient response of a one-dimensional,
      finite length waveguide. The field generated by arbitrary initial conditions is
      characterized by an infinite number of images, which leads to a representation of
      the acoustic field as oppositely propagating waves in an unbounded waveguide.
      Both graphical and mathematical descriptions of these waves are derived, with the
      former shown to provide significant insights. Mathematical analysis of the image
      construction leads to identification of several fundamental acoustic phenomena,
      including acoustic modes and reverberation time. From an instructional viewpoint
      the ability to explore fundamental acoustic phenomena without recourse to solving
      differential equations makes the waveform image concept especially useful as an
      introductory tool.

PMID- 16642810
TI  - High order approximate low frequency theory of elastic anisotropic lining and
      coating.
AB  - A problem of the dynamic behavior of an elastic layer coupled to one or two thick
      elastic solids is considered. All the materials may possess a general anisotropy
      and the layer is assumed to be thin enough with respect to the characteristic
      wavelength. Introducing the asymptotic power series with respect to the thickness
      over-wavelength ratio for the main quantities and using the asymptotic
      integration method the displacements and stresses on the layer surfaces are
      related. Thus, the so-called impedance boundary conditions (IBC) are deduced for
      three cases--for a coated substrate with given displacements or with given
      stresses on the surface and for two substrates with a layer in between. In
      contrast to previous papers these IBC are obtained for the most general situation
      with the asymptotic accuracy up to the sixth order, uniform with respect to the
      representation of the displacements and stresses. Presented theory can be used
      for studying the surface and interface phenomena as well as for calculating
      fields and spectra of layered solids. The results are validated numerically and
      compared with those of other authors.

PMID- 16642811
TI  - Generation of the basis sets for multi-Gaussian ultrasonic beam models--an
      overview.
AB  - By using a small number of Gaussian basis functions, one can synthesize the wave
      fields radiated from planar and focused piston transducers in the form of a
      superposition of Gaussian beams. Since Gaussian beams can be transmitted through
      complex geometries and media, such multi-Gaussian beam models have become
      powerful simulation tools. In previous studies the basis function expansion
      coefficients of multi-Gaussian beam models have been obtained by both spatial
      domain and k-space domain methods. Here, we will give an overview of these two
      methods and relate their expansion coefficients. We will demonstrate that the
      expansion coefficients that have been optimized for circular piston transducers
      can also be used to generate improved field simulations for rectangular probes.
      It will also be shown that because Gaussian beams are only approximate (paraxial)
      solutions to the wave equation, a multi-Gaussian beam model is ultimately limited
      in the accuracy it can obtain in the very near field.

PMID- 16642812
TI  - On using polynomial chaos for modeling uncertainty in acoustic propagation.
AB  - The use of polynomial chaos for incorporating environmental variability into
      propagation models is investigated in the context of a simplified one-dimensional
      model, which is relevant for acoustic propagation when the random sound speed is
      independent of depth. Environmental variability is described by a spectral
      representation of a stochastic process and the chaotic representation of the wave
      field then consists of an expansion in terms of orthogonal random polynomials.
      Issues concerning implementation of the relevant equations, the accuracy of the
      approximation, uniformity of the expansion over the propagation range, and the
      computational burden necessary to evaluate different field statistics are
      addressed. When the correlation length of the environmental fluctuations is
      small, low-order expansions work well, while for large correlation lengths the
      convergence of the expansion is highly range dependent and requires high-order
      approximants. These conclusions also apply in higher-dimensional propagation
      problems.

PMID- 16642813
TI  - Wave propagation in two-dimensional periodic lattices.
AB  - Plane wave propagation in infinite two-dimensional periodic lattices is
      investigated using Floquet-Bloch principles. Frequency bandgaps and spatial
      filtering phenomena are examined in four representative planar lattice
      topologies: hexagonal honeycomb, Kagome lattice, triangular honeycomb, and the
      square honeycomb. These topologies exhibit dramatic differences in their long
      wavelength deformation properties. Long-wavelength asymptotes to the dispersion
      curves based on homogenization theory are in good agreement with the numerical
      results for each of the four lattices. The slenderness ratio of the constituent
      beams of the lattice (or relative density) has a significant influence on the
      band structure. The techniques developed in this work can be used to design
      lattices with a desired band structure. The observed spatial filtering effects
      due to anisotropy at high frequencies (short wavelengths) of wave propagation are
      consistent with the lattice symmetries.

PMID- 16642814
TI  - Elastic wave propagation in sinusoidally corrugated waveguides.
AB  - The ultrasonic wave propagation in sinusoidally corrugated waveguides is studied
      in this paper. Periodically corrugated waveguides are gaining popularity in the
      field of vibration control and for designing structures with desired acoustic
      band gaps. Currently only numerical method (Boundary Element Method or Finite
      Element Method) based packages (e.g., PZFlex) are in principle capable of
      modeling ultrasonic fields in complex structures with rapid change of curvatures
      at the interfaces and boundaries but no analyses have been reported. However, the
      packages are very CPU intensive; it requires a huge amount of computation memory
      and time for its execution. In this paper a new semi-analytical technique called
      Distributed Point Source Method (DPSM) is used to model the ultrasonic field in
      sinusoidally corrugated waveguides immersed in water where the interface
      curvature changes rapidly. DPSM results are compared with analytical solutions.
      It is found that when a narrow ultrasonic beam hits the corrugation peaks at an
      angle, the wave propagates in the backward direction in waveguides with high
      corrugation depth. However, in waveguides with small corrugation the wave
      propagates in the forward direction. The forward and backward propagation
      phenomenon is found to be independent of the signal frequency and depends on the
      degree of corrugation.

PMID- 16642815
TI  - Curle's equation and acoustic scattering by a sphere.
AB  - Recent papers have initiated interesting comparisons between aeroacoustic theory
      and the results of acoustic scattering problems. In this paper, we consider some
      aspects of these comparisons for acoustic scattering by a sphere. We give a
      derivation of Curle's equation for a specific class of linear acoustic scattering
      problems, and, in response to previous claims to the contrary, give an explicit
      confirmation of Curle's equation for plane wave scattering by a stationary rigid
      sphere of arbitrary size in an inviscid fluid. We construct the complete solution
      for scattering by a rigid sphere in a viscous fluid, and show that the neglect of
      viscous terms in Curie's equation yields an incomplete prediction of the far
      field dipole pressure. We also consider the null field solution of the sphere
      scattering problem, and give its extension to the vorticity modes associated with
      viscosity. Finally, we construct a solution for an elastic sphere in a viscous
      fluid, and show that the rigid sphere/null field solution is recovered from the
      limit of infinite longitudinal and shear wave speeds in the elastic solid.

PMID- 16642816
TI  - Acoustical determination of the parameters governing viscous dissipation in
      porous media.
AB  - Analytical solutions are derived to extract from dynamic density the macroscopic
      parameters governing viscous dissipation of sound waves in open-cell porous
      media. While dynamic density is obtained from acoustical techniques, the
      analytical solutions are derived from the model describing this dynamic density.
      Here, semiphenomenological models by Johnson et al. and by Wilson are
      investigated. Assuming dynamic density, open porosity, and static airflow
      resistivity known, analytical solutions derived from the Johnson et al. model
      yield geometrical tortuosity and viscous characteristic dimension. For the Wilson
      model, only dynamic density needs to be known. In this case, analytical solutions
      yield-for the first time-Wilson's density parameter and vorticity-mode relaxation
      time. To alleviate constraints on the Johnson et al. model, an extrapolation
      approach is proposed to avoid prior knowledge of static resistivity. This
      approach may also be used to determine this latter parameter. The
      characterization methods are tested on three materials covering a wide range of
      static airflow resistivities (2300-150 100 Ns/m4), frame rigidities (soft and
      rigid), and pore geometries (cells and fibers). It is shown that the analytical
      solutions can be used to assess the validity of the descriptive models for a
      given material.

PMID- 16642817
TI  - Scattering of Rayleigh-Lamb waves by a surface breaking crack in an elastic
      plate.
AB  - This work studies the problem of scattering of Rayleigh-Lamb waves by a thin
      surface-breaking crack. The problem is solved by the projection method, which
      exploits some orthogonality relations deduced from the reciprocal theorem.
      Numerical results obtained by the projection method are compared with the results
      obtained using a finite element method reported by other authors for the case of
      a flat crack, finding good agreement. From the numerical results it is observed
      that, as the wave number of the incident wave, so for instance, is smaller, the
      reflected and transmitted energy corresponding to the converted mode, A0 in this
      case, are almost equal to each other. An explanation for this result is given,
      based on the asymptotic nature of the modes S0 and A0 for small wave numbers.

PMID- 16642818
TI  - Mode-matching without root-finding: application to a dissipative silencer.
AB  - This article presents an analytic mode-matching approach suitable for modelling
      the propagation of sound in a two-dimensional, three-part, ducting system. The
      approach avoids the need to find roots of the characteristic equation for the
      middle section of the duct (the component) and is readily applicable to a broad
      class of problems. It is demonstrated that the system of equations, derived via
      analytic mode-matching, exhibits certain features which ensure that they can be
      recast into a form that is independent of the roots of the characteristic
      equation for the component. The precise details of the component are irrelevant
      to the procedure; it is required only that there exists an orthogonality
      relation, or similar, for the eigenmodes corresponding to the propagating wave
      forms in this region. The method is applied here to a simple problem involving
      acoustic transmission through a dissipative silencer of the type commonly found
      in heating ventilation and air-conditioning ducts. With reference to this
      example, the silencer transmission loss is computed, and the power balance for
      the silencer is investigated and is shown to be an identity that is necessarily
      satisfied by the system of equations, regardless of the level of truncation.

PMID- 16642819
TI  - Impedance of a sphere oscillating in an elastic medium with and without slip.
AB  - The dynamic impedance of a sphere oscillating in an elastic medium is considered.
      Oestreicher's [J. Acoust. Soc. Am. 23, 707-714 (1951)] formula for the impedance
      of a sphere bonded to the surrounding medium can be expressed in a relatively
      simple form in terms of three lumped impedances associated with the displaced
      mass and the longitudinal and transverse waves. If the surface of the sphere
      slips while the normal velocity remains continuous, the impedance formula is
      modified by adjusting the definition of the transverse impedance to include the
      interfacial impedance.

PMID- 16642820
TI  - Bubble pulsations between parallel plates.
AB  - The dynamic response of an acoustically driven spherical bubble between parallel
      plates is investigated in the linear approximation. For the case of rigid plates,
      explicit expressions are provided for the resonance frequency and damping, and
      the importance of including compressibility of the liquid is discussed. For wide
      channels, approximate results are presented that account for finite acoustic
      impedance of the plates.

PMID- 16642821
TI  - Acoustic pulse propagation near a right-angle wall.
AB  - Experimental measurements were conducted around a right-angle wall to investigate
      the effect of this obstacle on sound propagation outdoors. Using small explosions
      as the source of the acoustic waves allowed reflected and diffracted arrivals to
      be discerned and investigated in detail. The measurements confirm that
      diffraction acts as a low-pass filter on acoustic waveforms in agreement with
      simple diffraction theory, reducing the peak pressure and broadening the waveform
      shape received by a sensor in the shadow zone. In addition, sensors mounted
      directly on the wall registered pressure doubling for nongrazing angles of
      incidence in line-of-sight conditions. A fast two-dimensional finite difference
      time domain (FDTD) model was developed and provided additional insight into the
      propagation around the wall. Calculated waveforms show good agreement with the
      measured waveforms.

PMID- 16642822
TI  - Sound generated by vortices in the presence of a porous half-cylinder mounted on
      a rigid plane.
AB  - The sound generated by a single vortex and by two identical vortices in the
      presence of a half-cylinder made of porous material mounted on a rigid horizontal
      plane is studied theoretically using the acoustic analogy and the matched
      asymptotic expansion method. Both longitudinal and transverse dipoles are
      observed upon the introduction of the porous cylinder, but the former is
      considerably stronger than the latter in all the cases studied. Results suggest
      that the amplitudes of the dipoles and the overall acoustical energy radiated can
      be higher than that in the rigid cylinder case under some suitable combinations
      of flow parameters, especially when the flow resistance inside the porous
      material seen by the vortices is very small.

PMID- 16642823
TI  - Calculation of amplitudes of acoustic normal modes from the reciprocity
      principle.
AB  - Recently, J. D. Achenbach [J. Acoust. Soc. Am. 116, 1481-1487 (2004)] put
      forward, on heuristic grounds, an elegant technique to calculate amplitudes of
      guided waves in an elastic solid. The technique is based on application of the
      reciprocity principle. In this article, the technique is applied to acoustic
      waveguides. A mathematical justification of the technique is obtained. The
      technique is extended to enable calculation of excitation coefficients of modes
      of both discrete and continuous spectra by a given sound source. The results are
      shown to be identical to those derived with the traditional methods that rely on
      integral transforms.

PMID- 16642824
TI  - Mean field of a low-frequency sound wave propagating in a fluctuating ocean.
AB  - Statistical characteristics of low-frequency sound waves propagating over long
      distances in a fluctuating ocean are important for many practical problems. In
      this paper, using the theory of multiple scattering, the mean field of a low
      frequency sound wave was analytically calculated. In these calculations, the
      ratio of the sound wavelength and the scale of random inhomogeneities can be
      arbitrary. Furthermore, the correlation function of inhomogeneities is expressed
      in terms of a modal spectrum (e.g., internal waves modes). The obtained mean
      sound field is expressed as a sum of normal modes that attenuate exponentially.
      It is shown that the extinction coefficients of the modes are linearly related to
      the spectrum of random inhomogeneities in the ocean. Measurements of the
      extinction coefficients can therefore be used for retrieving this spectrum. The
      mean sound field is calculated for both 3D and 2D geometries of sound
      propagation. The results obtained can be used to study the range of applicability
      of the 2D propagation model.

PMID- 16642825
TI  - Multiple ping sonar accuracy improvement using robust motion estimation and ping
      fusion.
AB  - Noise degrades the accuracy of sonar systems. We demonstrate a practical method
      for increasing the effective signal-to-noise ratio (SNR) by fusing time delay
      information from a burst of multiple sonar pings. This approach can be useful
      when there is no relative motion between the sonar and the target during the
      burst of sonar pinging. Otherwise, the relative motion degrades the fusion and
      therefore, has to be addressed before fusion can be used. In this paper, we
      present a robust motion estimation algorithm which uses information from multiple
      receivers to estimate the relative motion between pings in the burst. We then
      compensate for motion, and show that the fusion of information from the burst of
      motion compensated pings improves both the resilience to noise and sonar
      accuracy, consequently increasing the operating range of the sonar system.

PMID- 16642826
TI  - Elastic moduli approximation of higher symmetry for the acoustical properties of
      an anisotropic material.
AB  - The issue of how to define and determine an optimal acoustical fit to a set of
      anisotropic elastic constants is addressed. The optimal moduli are defined as
      those which minimize the mean-squared difference in the acoustical tensors
      between the given moduli and all possible moduli of a chosen higher material
      symmetry. The solution is shown to be identical to minimizing a Euclidean
      distance function, or equivalently, projecting the tensor of elastic stiffness
      onto the appropriate symmetry. This has implications for how to best select
      anisotropic constants to acoustically model complex materials.

PMID- 16642827
TI  - Model-based analysis of dispersion curves using chirplets.
AB  - Time-frequency representations, like the spectrogram or the scalogram, are widely
      used to characterize dispersive waves. The resulting energy distributions,
      however, suffer from the uncertainty principle, which complicates the allocation
      of energy to individual propagation modes (especially when the dispersion curves
      of these modes are close to each other in the time-frequency domain). This
      research applies the chirplet as a tool to analyze dispersive wave signals based
      on a dispersion model. The chirplet transform, a generalization of both the
      wavelet and the short-time Fourier transform, enables the extraction of
      components of a signal with a particular instantaneous frequency and group delay.
      An adaptive algorithm identifies frequency regions for which quantitative
      statements can be made about an individual mode's energy, and employs chirplets
      (locally adapted to a dispersion curve model) to extract the (proportional)
      energy distribution of that single mode from a multimode dispersive wave signal.
      The effectiveness of this algorithm is demonstrated on a multimode synthetic Lamb
      wave signal for which the ground-truth energy distribution is known for each
      mode. Finally, the robustness of this algorithm is demonstrated on real,
      experimentally measured Lamb wave signals by an adaption of a correlation
      technique developed in previous research.

PMID- 16642828
TI  - Active vibration control using an inertial actuator with internal damping.
AB  - Collocated direct velocity feedback with ideal point force actuators mounted on
      structures is unconditionally stable and generates active damping. When inertial
      actuators are used to generate the control force, the system can become unstable
      even for moderate velocity feedback gains due to an additional -180 degree phase
      lag introduced by the fundamental axial resonant mode of the inertial actuator.
      In this study a relative velocity sensor is used to implement an inner velocity
      feedback loop that generates internal damping in a lightweight, electrodynamic,
      inertial actuator. Simulation results for a model problem with the actuator
      mounted on a clamped plate show that, when internal relative velocity feedback is
      used in addition to a conventional external velocity feedback loop, there is an
      optimum combination of internal and external velocity feedback gains, which, for
      a given gain margin, maximizes vibration reduction. These predictions are
      validated in experiments with a specially built lightweight inertial actuator.

PMID- 16642829
TI  - Near-irreversibility in a conservative linear structure with singularity points
      in its modal density.
AB  - Through two complementary approaches, using modal response and wave propagation,
      the analyses presented here show the conditions under which a decaying impulse
      response, or a nearly irreversible energy trapping, takes place in a linear
      conservative continuous system. The results show that the basic foundation of
      near-irreversibility or apparent damping rests upon the presence of singularity
      points in the modal density of dynamic systems or, analogously, in the wave
      stopping properties associated with these singularities. To illustrate the
      concept of apparent damping in detail, a simple undamped beam is modified to
      introduce a singularity point in its modal density distribution. Simulations show
      that a suitable application of a compressive axial force to an undamped beam
      placed on an elastic foundation attenuates its impulse response with time and
      develops the characteristics of a nearly irreversible energy trap.

PMID- 16642830
TI  - The modeling of the radiation and response green's function of a fluid-loaded
      cylindrical shell with an external compliant layer.
AB  - Scattering and radiation of acoustic waves from a fluid-loaded cylindrical shell
      with an external compliant layer are of interest. The compliant layer can be
      modeled by a normally reacting impedance layer, which has the advantage that
      complex compliant layer geometries, such as partial compliant layers, can be
      considered. A question may, however, arise as to the accuracy of this approach. A
      more rigorous approach is to model the elastic shell and compliant layer using a
      multilayer shell theory, which has the disadvantage that it cannot be extended to
      consider partial layers. In this paper scattering results from the normally
      reacting compliant layer model are compared to those from the multilayer shell
      model to show that the two approaches produce similar results, except for
      thickness resonances of the compliant layer. Having established the consistency
      between the two approaches, results for the far-field acoustic radiation as a
      function of frequency and radiation angle for a fluid-loaded shell with an
      external compliant layer excited by an internal ring force are obtained using the
      normally reacting impedance layer model. These results clearly show the reduction
      in the far field radiation due to the presence of the compliant layer.

PMID- 16642831
TI  - Vibro-acoustic control with a distributed sensor network.
AB  - The purpose of this work is to demonstrate the ability of a distributed control
      system, based on a smart sensor network, to reduce acoustic radiation from a
      vibrating structure. The platform from which control is effected consists of a
      network of smart sensors, each referred to as a node. Each node possesses its own
      computational capability, sensor, actuator and the ability to communicate with
      other nodes via a wired or wireless network. The primary focus of this work is to
      employ existing group management middleware concepts to enable vibro-acoustic
      control with such a distributed network. Group management middleware is
      distributed software that provides for the establishment and maintenance of
      groups of distributed nodes and that provides for the network communication among
      such groups. The control objective is met by designing distributed feedback
      compensators that take advantage of node groups in order to effect their control.
      The node groups are formed based on physical proximity. The global control
      objective is to minimize the radiated sound power from a rectangular plate.
      Results of this investigation demonstrate that such a distributed control system
      can achieve attenuations comparable to those achieved by a centralized
      controller.

PMID- 16642832
TI  - Noise annoyance and activity disturbance before and after the erection of a
      roadside noise barrier.
AB  - Questionnaire studies were conducted in a residential area before and after the
      erection of a 2.25 m high noise barrier of conventional type along a heavily
      traveled road (19,600 vehicles/24 h). The interval between studies was two years.
      Houses closest to the barrier received a sound-level reduction from -70.0 to 62.5
      dB Lden at the most exposed facade. The sound-level reduction decreased with
      distance to the road, and was negligible for houses at more than 100 m distance.
      Up to this distance, the noise barrier reduced residents' noise annoyance
      outdoors and indoors as well as improved speech communication outdoors. Indoors,
      speech communication and sleep disturbance were slightly but nonsignificantly
      improved. Predictions of the number of annoyed persons from published exposure
      response curves (in Lden) agreed with the percentage of residents being annoyed
      when indoors, before and after the barrier. Conversely, the percentage of
      residents being annoyed when outdoors clearly exceeded the predictions. These
      results suggest that these exposure-response curves may be used in predicting
      indoor situations, but they should not be applied in situations where outdoor
      annoyance is at focus.

PMID- 16642833
TI  - Relaxation of sound fields in rooms of diffusely reflecting boundaries and its
      application in acoustical radiosity simulation.
AB  - The acoustical radiosity method is a computationally expensive acoustical
      simulation algorithm that assumes an enclosure with ideal diffuse reflecting
      boundaries. Miles observed that for such an enclosure, the sound energy decay of
      every point on the boundaries will gradually converge to exponential manner with
      a uniform decay rate. Therefore, the ratio of radiosity between every pair of
      points on the boundaries will converge to a constant, and the radiosity across
      the boundaries will approach a fixed distribution during the sound decay process,
      where radiosity is defined as the acoustic power per unit area leaving (or being
      received by) a point on a boundary. We call this phenomenon the "relaxation" of
      the sound field. In this paper, we study the relaxation in rooms of different
      shapes with different boundary absorptions. Criteria based on the relaxation of
      the sound field are proposed to terminate the costly and unnecessary radiosity
      computation in the later phase, which can then be replaced by a fast regression
      step to speed up the acoustical radiosity simulation.

PMID- 16642834
TI  - Effects of the inclination of a rigid wall on the free vibration characteristics
      of acoustic modes in a trapezoidal cavity.
AB  - The coupling between rigid-walled modes of a rectangular cavity (RC modes) is
      used to obtain the shapes and resonance frequencies of rigid-walled modes of a
      trapezoidal cavity (TC modes) with an inclined rigid wall. A method is
      established to identify the TC modes, where the modes can be defined to evolve
      from individual RC modes. The wall inclination generates two coupling mechanisms,
      namely, the local coupling where the RC modes couple at the inclined wall, and
      the global coupling where the RC modes couple throughout the trapezoidal volume.
      The latter arises from the nonorthogonality of the RC modes in the trapezoidal
      volume. Both couplings are selective that only RC modes with the same number of
      nodes in the direction perpendicular to the inclination are coupled to each
      other. For small inclinations, each TC mode possesses the distorted shape of the
      RC mode that evolves it. When the inclination is increased, the TC-mode shape
      becomes complicated and unrecognizable, and extrema can also exist in the
      resonance frequency of the TC mode. These behaviors are determined by the
      behaviors of the local and global couplings of the RC mode. This paper provides
      an understanding of how the free vibration characteristics of TC modes change
      with the inclination and what determines these changes.

PMID- 16642835
TI  - Mechanism and calculation of the niche effect in airborne sound transmission.
AB  - The goal is to interpret and calculate the "niche effect" for the airborne sound
      transmission through a specimen mounted inside an aperture in the wall between
      the source and receiving reverberation rooms. The low-frequency sound insulation
      is known to be worse for the specimen placed at the center than for the specimen
      mounted at either edge of the aperture. As shown, the aperture with a tested
      specimen can be simulated at low frequencies as a triple partition where the
      middle element is the specimen and the role of the edge leaves is played by the
      air masses entrained at the aperture edges. With a centrally located specimen,
      such a triple system is symmetric and has two main natural frequencies close
      together. In this case, the resonant transmission is higher than for the edge
      arrangement simulated as a double system with one natural frequency. Analogous
      resonant phenomena are known to reduce the low-frequency transmission loss for
      symmetric triple windows or solid walls with identical air gaps and lightweight
      boards on both sides. The theoretical results obtained for the mechanical and
      acoustical models are in a good agreement with the experimental data.

PMID- 16642836
TI  - Automatic determination of the number of targets present when using the time
      reversal operator.
AB  - Acoustical time reversal mirrors have been shown to provide a highly accurate
      means of studying and focusing on acoustical sources. The DORT method is a
      derivation of the time reversal process, which allows for focusing on multiple
      targets. An important step in this process is the determination of the number of
      targets or sources present. This is achieved by examining the eigenvalues of the
      time reversal operator (TRO). The number of significant eigenvalues is then
      chosen as the number of sources present. However, as mentioned in [N. Mordant, C.
      Prada, and M. Fink, J. Acoust. Soc. Am. 105, 2634-2642 (1999) and C. Prada, M.
      Tanter, and M. Fink, in Proceedings of the IEEE Symposium, 1997, pp. 679-683],
      factors such as low signal to noise ratio (SNR), small data sample, array
      configuration and the target location may result in the eigenvalues corresponding
      to the targets no longer being distinguishable from the background noise
      eigenvalues. This paper proposes a robust method of automatically determining the
      number of targets even in the presence of a small number of snapshots. For white
      Gaussian noise, the profile of the ordered eigenvalues is seen to fit an
      exponential law. The observed eigenvalues are then compared to this model and a
      mismatch is detected between the observed profile and the noise-only model. The
      index of the mismatch gives the number of scatterers present.

PMID- 16642837
TI  - Resonant modes in transiently evoked otoacoustic emissions and asymmetries
      between left and right ear.
AB  - A number of single-frequency resonant modes in click evoked otoacoustic emissions
      (OAEs) was investigated. The OAE modes were identified by means of an adaptive
      approximation method based on the matching pursuit (MP) algorithm. The signals
      were decomposed into basic waveforms coming from a very large and redundant
      dictionary of Gabor functions. The study was performed on transiently evoked
      otoacoustic emissions (TEOAEs) from left and right ears of 108 subjects. The
      correspondence between waveforms found by the procedure and resonant modes was
      shown (both for simulated noisy data and for single-person TEOAEs). The
      decomposition of TEOAEs made distinction between short and long-lasting
      components possible. The number of main resonant modes was studied by means of
      different criteria and they all led to similar results, indicating that the main
      features of the signal are explained on average by 10 waveforms. The same number
      of resonant modes for the right ear accounted for more energy than for the left
      ear.

PMID- 16642838
TI  - Cochlear transducer operating point adaptation.
AB  - The operating point (OP) of outer hair cell (OHC) mechanotransduction can be
      defined as any shift away from the center position on the transduction function.
      It is a dc offset that can be described by percentage of the maximum transduction
      current or as an equivalent dc pressure in the ear canal. The change of OP can be
      determined from the changes of the second and third harmonics of the cochlear
      microphonic (CM) following a calibration of its initial value. We found that the
      initial OP was dependent on sound level and cochlear sensitivity. From CM
      generated by a lower sound level at 74 dB SPL to avoid saturation and suppression
      of basal turn cochlear amplification, the OHC OP was at constant 57% of the
      maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the
      OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz
      best frequency location using a blunt probe. The force applied over the scala
      tympani induced an OP change as if the organ of Corti moved toward the scala
      vestibuli (SV) direction. During an application of the constant force, the second
      harmonic of the CM partially recovered toward the initial level, which could be
      described by two time constants. Removing the force induced recovery of the
      second harmonic to its normal level described by a single time constant. The
      force applied over the SV caused an opposite result. These data indicate an
      active mechanism for OHC transduction OP.

PMID- 16642839
TI  - Frequency- and level-dependent changes in auditory brainstem responses (ABRS) in
      developing mice.
AB  - The development of the auditory brainstem response was studied to quantitatively
      assess its dependence on stimulus frequency and level. Responses were not
      observed to stimuli > or =16 kHz on P12, however, the full range of responsive
      frequencies included in the study was observed by P14. Response thresholds were
      high on P12, exceeding 100 dB SPL for all stimuli tested. The rate of threshold
      development increased progressively for stimulus frequencies between -2 and 10
      kHz, with the most rapid changes occurring at frequencies >10 kHz. Adultlike
      thresholds were observed by P18. Response latencies and interpeak intervals
      matured rapidly over the course of the second and third postnatal weeks and did
      not achieve adultlike characteristics until after P18. Latencies of higher-order
      peaks were progressively and sequentially delayed relative to wave I. Wave I
      amplitudes developed nonmonotonically, growing during the first 24 days and
      stabilizing at adult values by approximately P36. Slopes of wave I amplitude-and
      latency-level curves were significantly steeper than those of adults during the
      neonatal period and the outcome of input-output analyses, as well as frequency
      specific maturational profiles, support developmental models in which function
      initially matures in the mid-frequency range and proceeds, simultaneously, in
      both apical and basal directions.

PMID- 16642840
TI  - Binaural detection with narrowband and wideband reproducible noise maskers. III.
      Monaural and diotic detection and model results.
AB  - A single-interval, yes-no, tone-in-noise detection experiment was conducted to
      measure the proportion of "tone present" responses to each of 25 reproducible
      noise-alone and tone-plus-noise waveforms under narrowband (100 Hz), wideband
      (2900 Hz), monotic, and diotic stimulus conditions. Proportions of "tone present"
      responses (estimates of the probabilities of hits and false alarms) were
      correlated across masker bandwidths and across monotic and diotic conditions. Two
      categories of models were considered; one based on stimulus energy or neural
      counts, and another based on temporal structure of the stimulus envelope or
      neural patterns. Both categories gave significant correlation between decision
      variables and data. A model based on a weighted combination of energy in multiple
      critical bands performed best, predicting up to 90% of the variance in the
      reproducible-noise data. However, since energy-based models are unable to
      successfully explain detection under a roving-level paradigm without substantial
      modification, it is argued that other variations of detection models must be
      considered for future study. Temporal models are resistant to changes in
      threshold under roving-level conditions, but explained at most only 67% of the
      variance in the reproducible-noise data.

PMID- 16642841
TI  - Sensitivity to isolated and concurrent intensity and fundamental frequency
      increments by cochlear implant users under natural listening conditions.
AB  - Sensitivity to acoustic cues in cochlear implant (CI) listening under natural
      conditions is a potentially complex interaction between a number of simultaneous
      factors, and may be difficult to predict. In the present study, sensitivity was
      measured under conditions that approximate those of natural listening.
      Synthesized words having increases in intensity or fundamental frequency (F0) in
      a middle stressed syllable were presented in soundfield to normal-hearing
      listeners and to CI listeners using their everyday speech processors and
      programming. In contrast to the extremely fine sensitivity to electrical current
      observed when direct stimulation of single electrodes is employed, difference
      limens (DLs) for intensity were larger for the CI listeners by a factor of 2.4.
      In accord with previous work, F0 DLs were larger by almost one order of
      magnitude. In a second experiment, it was found that the presence of concurrent
      intensity and F0 increments reduced the mean DL to half that of either cue alone
      for both groups of subjects, indicating that both groups combine concurrent cues
      with equal success. Although sensitivity to either cue in isolation was not
      related to word recognition in CI users, the listeners having lower combined-cue
      thresholds produced better word recognition scores.

PMID- 16642842
TI  - Compensation following real-time manipulation of formants in isolated vowels.
AB  - Auditory feedback influences human speech production, as demonstrated by studies
      using rapid pitch and loudness changes. Feedback has also been investigated using
      the gradual manipulation of formants in adaptation studies with whispered speech.
      In the work reported here, the first formant of steady-state isolated vowels was
      unexpectedly altered within trials for voiced speech. This was achieved using a
      real-time formant tracking and filtering system developed for this purpose. The
      first formant of vowel /epsilon/ was manipulated 100% toward either /ae/ or /I/,
      and participants responded by altering their production with average Fl
      compensation as large as 16.3% and 10.6% of the applied formant shift,
      respectively. Compensation was estimated to begin <460 ms after stimulus onset.
      The rapid formant compensations found here suggest that auditory feedback control
      is similar for both F0 and formants.

PMID- 16642843
TI  - Coherence detection: effects of frequency, frequency uncertainty, and
      onset/offset delays.
AB  - The detectability of a sequence of equal-frequency (coherent) tonal components
      embedded in random, multiburst maskers was evaluated. The masker was comprised of
      tonal components located in a time-by-frequency spectrogram with eight 30 ms time
      columns and 29 frequency rows ranging logarithmically from 200 to 5000 Hz. The
      probability that a tone occurred in any one cell of the spectrogram, p, was the
      independent variable. The signal and masker components were of equal duration and
      equal level. Using a yes/no procedure, threshold values of p were estimated for
      five signal frequencies (220, 445, 1000, 2245, 4490 Hz) and when the signal
      frequency was random. Thresholds were worst for the random-frequency signal and
      best for the fixed 1000 Hz signal. In additional conditions, the value of p was
      fixed and the signal components were delayed relative to the masker components. A
      1 ms delay provided better sensitivity (d' grew from 0.5 to 1) for all but the
      lowest signal frequency tested. An analysis of no-signal trials revealed that
      false alarm rates were higher when components falling at the signal frequency
      were consecutive than when they were distributed across bursts. Thus, coherence
      rather than total energy at the signal frequency is important for signal
      detection.

PMID- 16642844
TI  - Temporal processing deficits in the pre-senescent auditory system.
AB  - This study tested the hypothesis that temporal processing deficits are evident in
      the pre-senescent (middle-aged) auditory system for listening tasks that involve
      brief stimuli, across-frequency-channel processing, and/or significant processing
      loads. A gap duration discrimination (GDD) task was employed that used either
      fixed-duration gap markers (experiment 1) or random-duration markers (experiment
      2). Independent variables included standard gap duration (0, 35, and 250 ms),
      marker frequency (within- and across-frequency), and task complexity. A total of
      18 young and 23 middle-aged listeners with normal hearing participated in the GDD
      experiments. Middle age was defined operationally as 40-55 years of age. The
      results indicated that middle-aged listeners performed more poorly than the young
      listeners in general, and that this deficit was sometimes, but not always,
      exacerbated by increases in task complexity. A third experiment employed a
      categorical perception task that measured the gap duration associated with a
      perceptual boundary. The results from 12 young and 12 middle-aged listeners with
      normal hearing indicated that the categorical boundary was associated with
      shorter gaps in the young listeners. The results of these experiments indicate
      that temporal processing deficits can be observed relatively early in the aging
      process, and are evident in middle age.

PMID- 16642845
TI  - Age-related changes in within- and between-channel gap detection using sinusoidal
      stimuli.
AB  - Pure tone gap stimuli with identical (within-channel) or dissimilar (between
      channel) marker frequencies of 1 and 2 kHz were presented to young and old
      listeners in a two-interval forced choice gap detection task. To estimate the
      influence of extraneous duration cues on gap detection, thresholds in the between
      channel conditions were obtained for two different sets of reference stimuli:
      reference stimuli that were matched to the overall duration of the gap stimulus,
      i.e., two markers plus the gap, and reference stimuli that were fixed at the
      combined duration of the two markers excluding the gap. Results from within
      channel conditions were consistent with previous studies, i.e., there were small
      but highly reliable age differences, smaller gap thresholds at longer marker
      durations, and an interaction between the two variables. In between-channel
      conditions, however, age differences were not as clear cut. Rather, the effect of
      age varied as a function of duration cue and was more pronounced when stimuli
      were matched for overall duration than when the duration of the reference tone
      was fixed.

PMID- 16642846
TI  - Monaural speech segregation using synthetic speech signals.
AB  - When listening to natural speech, listeners are fairly adept at using cues such
      as pitch, vocal tract length, prosody, and level differences to extract a target
      speech signal from an interfering speech masker. However, little is known about
      the cues that listeners might use to segregate synthetic speech signals that
      retain the intelligibility characteristics of speech but lack many of the
      features that listeners normally use to segregate competing talkers. In this
      experiment, intelligibility was measured in a diotic listening task that required
      the segregation of two simultaneously presented synthetic sentences. Three types
      of synthetic signals were created: (1) sine-wave speech (SWS); (2) modulated
      noise-band speech (MNB); and (3) modulated sine-band speech (MSB). The listeners
      performed worse for all three types of synthetic signals than they did with
      natural speech signals, particularly at low signal-to-noise ratio (SNR) values.
      Of the three synthetic signals, the results indicate that SWS signals preserve
      more of the voice characteristics used for speech segregation than MNB and MSB
      signals. These findings have implications for cochlear implant users, who rely on
      signals very similar to MNB speech and thus are likely to have difficulty
      understanding speech in cocktail-party listening environments.

PMID- 16642847
TI  - A geometric representation of spectral and temporal vowel features:
      quantification of vowel overlap in three linguistic varieties.
AB  - A geometrical method for computing overlap between vowel distributions, the
      spectral overlap assessment metric (SOAM), is applied to an investigation of
      spectral (F1, F2) and temporal (duration) relations in three different types of
      systems: one claimed to exhibit primary quality (American English), one primary
      quantity (Jamaican Creole), and one about which no claims have been made
      (Jamaican English). Shapes, orientations, and proximities of pairs of vowel
      distributions involved in phonological oppositions are modeled using best-fit
      ellipses (in F1 x F2 space) and ellipsoids (F1 x F2 x duration). Overlap
      fractions computed for each pair suggest that spectral and temporal features
      interact differently in the three varieties and oppositions. Under a two
      dimensional analysis, two of three American English oppositions show no overlap;
      the third shows partial overlap. All Jamaican Creole oppositions exhibit complete
      overlap when F1 and F2 alone are modeled, but no or partial overlap with
      incorporation of a factor for duration. Jamaican English three-dimensional
      overlap fractions resemble two-dimensional results for American English. A
      multidimensional analysis tool such as SOAM appears to provide a more objective
      basis for simultaneously investigating spectral and temporal relations within
      vowel systems. Normalization methods and the SOAM method are described in an
      extended appendix.

PMID- 16642848
TI  - Dependence of phonation threshold pressure on vocal tract acoustics and vocal
      fold tissue mechanics.
AB  - Analytical and computer simulation studies have shown that the acoustic impedance
      of the vocal tract as well as the viscoelastic properties of vocal fold tissues
      are critical for determining the dynamics and the energy transfer mechanism of
      vocal fold oscillation. In the present study, a linear, small-amplitude
      oscillation theory was revised by taking into account the propagation of a
      mucosal wave and the inertive reactance (inertance) of the supraglottal vocal
      tract as the major energy transfer mechanisms for flow-induced self-oscillation
      of the vocal fold. Specifically, analytical results predicted that phonation
      threshold pressure (Pth) increases with the viscous shear properties of the vocal
      fold, but decreases with vocal tract inertance. This theory was empirically
      tested using a physical model of the larynx, where biological materials (fat,
      hyaluronic acid, and fibronectin) were implanted into the vocal fold cover to
      investigate the effect of vocal fold tissue viscoelasticity on Pth. A uniform
      tube supraglottal vocal tract was also introduced to examine the effect of vocal
      tract inertance on Pth. Results showed that Pth decreased with the inertive
      impedance of the vocal tract and increased with the viscous shear modulus (G") or
      dynamic viscosity (eta') of the vocal fold cover, consistent with theoretical
      predictions. These findings supported the potential biomechanical benefits of
      hyaluronic acid as a surgical bioimplant for repairing voice disorders involving
      the superficial layer of the lamina propria, such as scarring, sulcus vocalis,
      atrophy, and Reinke's edema.

PMID- 16642849
TI  - Vocal responses to unanticipated perturbations in voice loudness feedback: an
      automatic mechanism for stabilizing voice amplitude.
AB  - The present study tested whether subjects respond to unanticipated short
      perturbations in voice loudness feedback with compensatory responses in voice
      amplitude. The role of stimulus magnitude (+/- 1,3 vs 6 dB SPL), stimulus
      direction (up vs down), and the ongoing voice amplitude level (normal vs soft)
      were compared across compensations. Subjects responded to perturbations in voice
      loudness feedback with a compensatory change in voice amplitude 76% of the time.
      Mean latency of amplitude compensation was 157 ms. Mean response magnitudes were
      smallest for 1-dB stimulus perturbations (0.75 dB) and greatest for 6-dB
      conditions (0.98 dB). However, expressed as gain, responses for 1-dB
      perturbations were largest and almost approached 1.0. Response magnitudes were
      larger for the soft voice amplitude condition compared to the normal voice
      amplitude condition. A mathematical model of the audio-vocal system captured the
      main features of the compensations. Previous research has demonstrated that
      subjects can respond to an unanticipated perturbation in voice pitch feedback
      with an automatic compensatory response in voice fundamental frequency. Data from
      the present study suggest that voice loudness feedback can be used in a similar
      manner to monitor and stabilize voice amplitude around a desired loudness level.

PMID- 16642850
TI  - Electropalatographic, acoustic, and perceptual data on adaptation to a palatal
      perturbation.
AB  - Exploring the compensatory responses of the speech production system to
      perturbation has provided valuable insights into speech motor control. The
      present experiment was conducted to examine compensation for one such
      perturbation-a palatal perturbation in the production of the fricative /s/.
      Subjects wore a specially designed electropalatographic (EPG) appliance with a
      buildup of acrylic over the alveolar ridge as well as a normal EPG palate. In
      this way, compensatory tongue positioning could be assessed during a period of
      target specific and intense practice and compared to nonperturbed conditions.
      Electropalatographic, acoustic, and perceptual analyses of productions of /asa/
      elicited from nine speakers over the course of a one-hour practice period were
      conducted. Acoustic and perceptual results confirmed earlier findings, which
      showed improvement in production with a thick artificial palate in place over the
      practice period; the EPG data showed overall increased maximum contact as well as
      increased medial and posterior contact for speakers with the thick palate in
      place, but little change over time. Negative aftereffects were observed in the
      productions with the thin palate, indicating recalibration of sensorimotor
      processes in the face of the oral-articulatory perturbation. Findings are
      discussed with regard to the nature of adaptive articulatory skills.

PMID- 16642851
TI  - On phonetic convergence during conversational interaction.
AB  - Following research that found imitation in single-word shadowing, this study
      examines the degree to which interacting talkers increase similarity in phonetic
      repertoire during conversational interaction. Between-talker repetitions of the
      same lexical items produced in a conversational task were examined for phonetic
      convergence by asking a separate set of listeners to detect similarity in
      pronunciation across items in a perceptual task. In general, a listener judged a
      repeated item spoken by one talker in the task to be more similar to a sample
      production spoken by the talker's partner than corresponding pre- and
      postinteraction utterances. Both the role of a participant in the task and the
      sex of the pair of talkers affected the degree of convergence. These results
      suggest that talkers in conversational settings are susceptible to phonetic
      convergence, which can mark nonlinguistic functions in social discourse and can
      form the basis for phenomena such as accent change and dialect formation.

PMID- 16642852
TI  - Perceptual invariance of coarticulated vowels over variations in speaking rate.
AB  - This study examined the perception and acoustics of a large corpus of vowels
      spoken in consonant-vowel-consonant syllables produced in citation-form (lists)
      and spoken in sentences at normal and rapid rates by a female adult. Listeners
      correctly categorized the speaking rate of sentence materials as normal or rapid
      (2% errors) but did not accurately classify the speaking rate of the syllables
      when they were excised from the sentences (25% errors). In contrast, listeners
      accurately identified the vowels produced in sentences spoken at both rates when
      presented the sentences and when presented the excised syllables blocked by
      speaking rate or randomized. Acoustical analysis showed that formant frequencies
      at syllable midpoint for vowels in sentence materials showed "target undershoot"
      relative to citation-form values, but little change over speech rate. Syllable
      durations varied systematically with vowel identity, speaking rate, and voicing
      of final consonant. Vowel-inherent-spectral-change was invariant in direction of
      change over rate and context for most vowels. The temporal location of maximum F1
      frequency further differentiated spectrally adjacent lax and tense vowels. It was
      concluded that listeners were able to utilize these rate- and context-independent
      dynamic spectrotemporal parameters to identify coarticulated vowels, even when
      sentential information about speaking rate was not available.

PMID- 16642853
TI  - Stimulus variability and the phonetic relevance hypothesis: effects of
      variability in speaking style, fundamental frequency, and speaking rate on spoken
      word identification.
AB  - Three experiments were conducted to examine the effects of trial-to-trial
      variations in speaking style, fundamental frequency, and speaking rate on
      identification of spoken words. In addition, the experiments investigated whether
      any effects of stimulus variability would be modulated by phonetic confusability
      (i.e., lexical difficulty). In Experiment 1, trial-to-trial variations in
      speaking style reduced the overall identification performance compared with
      conditions containing no speaking-style variability. In addition, the effects of
      variability were greater for phonetically confusable words than for phonetically
      distinct words. In Experiment 2, variations in fundamental frequency were found
      to have no significant effects on spoken word identification and did not interact
      with lexical difficulty. In Experiment 3, two different methods for varying
      speaking rate were found to have equivalent negative effects on spoken word
      recognition and similar interactions with lexical difficulty. Overall, the
      findings are consistent with a phonetic-relevance hypothesis, in which
      accommodating sources of acoustic-phonetic variability that affect phonetically
      relevant properties of speech signals can impair spoken word identification. In
      contrast, variability in parameters of the speech signal that do not affect
      phonetically relevant properties are not expected to affect overall
      identification performance. Implications of these findings for the nature and
      development of lexical representations are discussed.

PMID- 16642854
TI  - Effects of introducing unprocessed low-frequency information on the reception of
      envelope-vocoder processed speech.
AB  - This study investigated the benefits of adding unprocessed low-frequency
      information to acoustic simulations of cochlear-implant processing in normal
      hearing listeners. Implant processing was simulated using an eight-channel noise
      excited envelope vocoder, and low-frequency information was added by replacing
      the lower frequency channels of the processor with a low-pass-filtered version of
      the original stimulus. Experiment 1 measured sentence-level speech reception as a
      function of target-to-masker ratio, with either steady-state speech-shaped noise
      or single-talker maskers. Experiment 2 measured listeners' ability to identify
      two vowels presented simultaneously, as a function of the F0 difference between
      the two vowels. In both experiments low-frequency information was added below
      either 300 or 600 Hz. The introduction of the additional low-frequency
      information led to substantial and significant improvements in performance in
      both experiments, with a greater improvement observed for the higher (600 Hz)
      than for the lower (300 Hz) cutoff frequency. However, performance never equaled
      performance in the unprocessed conditions. The results confirm other recent
      demonstrations that added low-frequency information can provide significant
      benefits in intelligibility, which may at least in part be attributed to
      improvements in F0 representation. The findings provide further support for
      efforts to make use of residual acoustic hearing in cochlear-implant users.

PMID- 16642855
TI  - The influence of perceived sexual orientation on fricative identification.
AB  - Listeners are more likely to hear a synthetic fricative ambiguous between /s/ and
      /integral/ as /integral/ if it is appended to a woman's voice than a man's voice
      [Strand and Johnson, in Natural Language Processing and Speech Technology:
      Results of the 3rd KONVENS Conference (Mouton de Gruyter, Berlin, 1996), pp. 14
      26]. This study expanded on this finding by replicating the result with a much
      larger group of male and female talkers than had been examined previously, by
      examining whether phonetic context mediates the influence of talker sex on
      fricative identification, and by examining whether talkers' perceived sexual
      orientation influences fricative identification. Stimuli were created by pairing
      a synthetic nine-step /s/-/integral/ continuum with tokens of /ae k/ and /Ip/
      taken from productions of shack and ship by 44 talkers whose perceived sexual
      orientation had been reported previously [Munson et al., J. Phonetics (in
      press)]. Listeners participated in a series of two-alternative sack-shack and sip
      ship identification experiments. Listeners identified more /integral/ tokens for
      women's voices than for men's voices for both continua. Lesbian/bisexual-sounding
      women elicited more sack and sip responses than heterosexual-sounding women. No
      consistent influence of perceived sexual orientation on fricative identification
      was noted for men's voices. Results suggest that listeners are sensitive to the
      association between fricatives' center frequencies and perceived sexual
      orientation in women's voices, but not in men's voices.

PMID- 16642856
TI  - The ability of listeners to use recovered envelope cues from speech fine
      structure.
AB  - Recent work has demonstrated that auditory filters recover temporal-envelope cues
      from speech fine structure when the former were removed by filtering or
      distortion. This study extended this work by assessing the contribution of
      recovered envelope cues to consonant perception as a function of the analysis
      bandwidth, when vowel-consonant-vowel (VCV) stimuli were processed in order to
      keep their fine structure only. The envelopes of these stimuli were extracted at
      the output of a bank of auditory filters and applied to pure tones whose
      frequency corresponded to the original filters' center frequencies. The resulting
      stimuli were found to be intelligible when the envelope was extracted from a
      single, wide analysis band. However, intelligibility decreases from one to eight
      bands with no further decrease beyond this value, indicating that the recovered
      envelope cues did not play a major role in consonant perception when the analysis
      bandwidth was narrower than four times the bandwidth of a normal auditory filter
      (i.e., number of analysis bands > or =8 for frequencies spanning 80 to 8020 Hz).

PMID- 16642857
TI  - Effect of masker type on native and non-native consonant perception in noise.
AB  - Spoken communication in a non-native language is especially difficult in the
      presence of noise. This study compared English and Spanish listeners' perceptions
      of English intervocalic consonants as a function of masker type. Three maskers
      (stationary noise, multitalker babble, and competing speech) provided varying
      amounts of energetic and informational masking. Competing English and Spanish
      speech maskers were used to examine the effect of masker language. Non-native
      performance fell short of that of native listeners in quiet, but a larger
      performance differential was found for all masking conditions. Both groups
      performed better in competing speech than in stationary noise, and both suffered
      most in babble. Since babble is a less effective energetic masker than stationary
      noise, these results suggest that non-native listeners are more adversely
      affected by both energetic and informational masking. A strong correlation was
      found between non-native performance in quiet and degree of deterioration in
      noise, suggesting that non-native phonetic category learning can be fragile. A
      small effect of language background was evident: English listeners performed
      better when the competing speech was Spanish.

PMID- 16642858
TI  - Age-related differences in identification and discrimination of temporal cues in
      speech segments.
AB  - This study investigated age-related differences in sensitivity to temporal cues
      in modified natural speech sounds. Listeners included young noise-masked
      subjects, elderly normal-hearing subjects, and elderly hearing-impaired subjects.
      Four speech continua were presented to listeners, with stimuli from each
      continuum varying in a single temporal dimension. The acoustic cues varied in
      separate continua were voice-onset time, vowel duration, silence duration, and
      transition duration. In separate conditions, the listeners identified the word
      stimuli, discriminated two stimuli in a same-different paradigm, and
      discriminated two stimuli in a 3-interval, 2-alternative forced-choice procedure.
      Results showed age-related differences in the identification function crossover
      points for the continua that varied in silence duration and transition duration.
      All listeners demonstrated shorter difference limens (DLs) for the three-interval
      paradigm than the two-interval paradigm, with older hearing-impaired listeners
      showing larger DLs than the other listener groups for the silence duration cue.
      The findings support the general hypothesis that aging can influence the
      processing of specific temporal cues that are related to consonant manner
      distinctions.

PMID- 16642859
TI  - Synchronization of organ pipes: experimental observations and modeling.
AB  - We report measurements on the synchronization properties of organ pipes. First,
      we investigate influence of an external acoustical signal from a loudspeaker on
      the sound of an organ pipe. Second, the mutual influence of two pipes with
      different pitch is analyzed. In analogy to the externally driven, or mutually
      coupled self-sustained oscillators, one observes a frequency locking, which can
      be explained by synchronization theory. Further, we measure the dependence of the
      frequency of the signals emitted by two mutually detuned pipes with varying
      distance between the pipes. The spectrum shows a broad "hump" structure, not
      found for coupled oscillators. This indicates a complex coupling of the two organ
      pipes leading to nonlinear beat phenomena.

PMID- 16642860
TI  - Noncontact modal analysis of a pipe organ reed using airborne ultrasound
      stimulated vibrometry.
AB  - The goal of this study was to excite and measure, in a noncontact manner, the
      vibrational modes of the reed from a reed organ pipe. To perform ultrasound
      stimulated excitation, the audio-range difference frequency between a pair of
      ultrasound beams produced a radiation force that induced vibrations. The
      resulting vibrational deflection shapes were measured with a scanning laser
      vibrometer. The resonances of any relatively small object can be studied in air
      using this technique. For a 36 mm x 6 mm brass reed, displacements and velocities
      in excess of 5 microm and 4 mm/s could be imparted at the fundamental frequency
      of 145 Hz. Using the same ultrasound transducer, excitation across the entire
      range of audio frequencies was obtained. Since the beam was focused on the reed,
      ultrasound stimulated excitation eliminated background effects observed during
      mechanical shaker excitation, such as vibrations of clamps and supports. The
      results obtained using single, dual and confocal ultrasound transducers in AM and
      two-beam modes, along with results obtained using a mechanical shaker and audio
      excitation using a speaker are discussed.

PMID- 16642861
TI  - Effect of the glottal source and the vocal tract on the partials amplitude of
      vibrato in male voices.
AB  - In this paper the production of vocal vibrato is investigated. The most relevant
      features of the acoustical vibrato signal, frequency and amplitude variations of
      the partials, will be related to the voice production features, glottal source
      (GS) and vocal tract response (VTR). Unlike previous related works, in this
      approach, the effect on the amplitude variations of the partials of each one of
      the above-mentioned voice production features will be identified in recordings of
      natural singing voice. Moreover, we will take special care of the reliability of
      the measurements, and, to this aim, a noninteractive vibrato production model
      will be also proposed in order to describe the vibrato production process and,
      more importantly, validate the measurements carried out in natural vibrato. Based
      on this study, it will be shown that during a few vibrato cycles, the glottal
      pulse characteristics, as well as the VTR, do not significantly change, and only
      the fundamental frequency of the GS varies. As a result, the pitch variations can
      be attributed to the GS, and these variations, along with the vocal tract
      filtering effect, will result in frequency and amplitude variations of the
      acoustic signal partials.

PMID- 16642862
TI  - Bayesian analysis of polyphonic western tonal music.
AB  - This paper deals with the computational analysis of musical audio from recorded
      audio waveforms. This general problem includes, as subtasks, music transcription,
      extraction of musical pitch, dynamics, timbre, instrument identity, and source
      separation. Analysis of real musical signals is a highly ill-posed task which is
      made complicated by the presence of transient sounds, background interference, or
      the complex structure of musical pitches in the time-frequency domain. This paper
      focuses on models and algorithms for computer transcription of multiple musical
      pitches in audio, elaborated from previous work by two of the authors. The audio
      data are supposedly presegmented into fixed pitch regimes such as individual
      chords. The models presented apply to pitched (tonal) music and are formulated
      via a Gabor representation of nonstationary signals. A Bayesian probabilistic
      structure is employed for representation of prior information about the
      parameters of the notes. This paper introduces a numerical Bayesian inference
      strategy for estimation of the pitches and other parameters of the waveform. The
      improved algorithm is much quicker and makes the approach feasible in realistic
      situations. Results are presented for estimation of a known number of notes
      present in randomly generated note clusters from a real musical instrument
      database.

PMID- 16642863
TI  - Investigation of superharmonic sound propagation and imaging in biological
      tissues in vitro.
AB  - This article presents both theoretical and experimental studies on the
      superharmonic generation and its imaging in biological tissues. A superharmonic
      component is defined as a summation of the third-, fourth-, and fifth-order
      harmonics. A superharmonic signal is produced using an 8-mm-diam, 2.5-MHz planar
      piston source that is excited by eight-cycle, 2.5-MHz tone bursts. Axial and
      lateral field distributions of the superharmonic component and the second
      harmonic are first calculated based on the nonlinear KZK model and then compared
      with those experimentally determined at two different source pressures of 0.5 and
      1 MPa. Results indicate that the amplitude of the superharmonic component can
      exceed that of the second harmonic, depending on the axial distance and the
      fundamental pressure amplitude. Also, the 3-dB beamwidth of the superharmonic
      component is about 23% narrower than that of the second harmonic. Additional
      experiments are performed in vitro using liver and fatty tissues in transmission
      mode and produced two-dimensional images using the fundamental, the second
      harmonic, and the superharmonic signals. Although the clinical applicability of
      this work still needs to be assessed, these results indicate that the
      superharmonic image quality is better than that of the other two images.

PMID- 16642864
TI  - Perception of complex sounds in budgerigars (Melopsittacus undulatus) with
      temporary hearing loss.
AB  - Songbirds and parrots deafened as nestlings fail to develop normal vocalizations,
      while birds deafened as adults show a gradual deterioration in the quality and
      precision of vocal production. Beyond this, little is known about the effect of
      hearing loss on the perception of vocalizations. Here, we induced temporary
      hearing loss in budgerigars with kanamycin and tested several aspects of the
      hearing, including the perception of complex, species-specific vocalizations. The
      ability of these birds to discriminate among acoustically distinct vocalizations
      was not impaired but the ability to make fine-grain discriminations among
      acoustically similar vocalizations was affected, even weeks after the basilar
      papilla had been repopulated with new hair cells. Interestingly, these birds were
      initially unable to recognize previously familiar contact calls in a
      classification task-suggesting that previously familiar vocalizations sounded
      unfamiliar with new hair cells. Eventually, in spite of slightly elevated
      absolute thresholds, the performance of birds on discrimination and perceptual
      recognition of vocalizations tasks returned to original levels. Thus, even though
      vocalizations may initially sound different with new hair cells, there are only
      minimal long-term effects of temporary hearing loss on auditory perception,
      recognition of species-specific vocalizations, or other aspects of acoustic
      communication in these birds.

PMID- 16642865
TI  - Polling the effective neighborhoods of spoken words with the verbal
      transformation effect.
AB  - Studies of the effects of lexical neighbors upon the recognition of spoken words
      have generally assumed that the most salient competitors differ by a single
      phoneme. The present study employs a procedure that induces the listeners to
      perceive and call out the salient competitors. By presenting a recording of a
      monosyllable repeated over and over, perceptual adaptation is produced, and
      perception of the stimulus is replaced by perception of a competitor. Reports
      from groups of subjects were obtained for monosyllables that vary in their
      frequency-weighted neighborhood density. The findings are compared with
      predictions based upon the neighborhood activation model.

PMID- 16642866
TI  - Not 'part of the job'. Nurses want to put an end to workplace violence.

PMID- 16642867
TI  - The Center continues focus on patient safety.

PMID- 16642868
TI  - Use of and resistance to antimicrobials.

PMID- 16642869
TI  - Safety testing of chemicals with a high likelihood of humans being exposed to
      them is a reasonable public health policy.

PMID- 16642870
TI  - Isolation of Mycobacterium bovis from a wood bison in a wildlife conservation
      project in the Northwest Territories.

PMID- 16642871
TI  - Conference report. Agriculture's role in managing antimicrobial resistance: the
      road to prudent use. October 23-26, 2005, Toronto, Canada.

PMID- 16642872
TI  - Ventral laparoscopic abomasopexy on adult cows.
AB  - Displacement of the abomasum is frequently diagnosed by veterinarians in bovine
      practice and numerous surgical techniques have been developed to treat and
      prevent this condition. Complications secondary to those techniques are related
      to their degree of invasiveness and the development of postoperative wound
      infections. The objectives of this study were to describe a safe and reliable
      abomasopexy technique by laparoscopy and to assess postoperative adhesion
      formation. A ventral laparoscopic abomasopexy was performed on 10 adult dry cows.
      The abomasum was fixed with 4 simple interrupted sutures using USP 2
      polydioxanone suture material. No major complications were encountered during the
      surgery. Abomasal adhesions were visually evaluated by laparoscopy 3 mo
      postoperatively. This technique proved to be simple and safe, and it provided
      adequate abomasum fixation in healthy dry cows. It could be used to surgically
      correct left displaced abomasum.

PMID- 16642873
TI  - Nasal chondrosarcoma in a Simmental cow.
AB  - The pathologic features of a nasal chondrosarcoma, a rare tumor of bovines, in a
      Simmental cow are described. Upon clinical examination, stertor, difficulty in
      breathing, poor body condition, and a nasal mass were found. Histopathologic
      examination revealed that the mass was composed mostly of numerous cartilaginous
      lobules surrounded by spindle-shaped cells, often showing mitotic figures,
      atypical chondrocytes, and lacunae containing 2 or more cells. On the basis of
      the histological features, the mass was diagnosed as a nasal chondrosarcoma.

PMID- 16642874
TI  - Perioperative use of analgesics in dogs and cats by Canadian veterinarians in
      2001.
AB  - A random sample of 652 Canadian veterinarians was surveyed to determine
      perioperative use of analgesics in dogs and cats following common surgeries. The
      response rate was 57.8%. With the exception of taildocking in puppies, at least
      85% of animals received preincisional analgesics, and 30% to 98.1% received
      postincisional analgesics. A similar survey was conducted in 1994; since then,
      analgesic usage has increased markedly, as have ratings of the pain caused by
      different surgeries. In 2001 most veterinarians (62%) used at least 2 classes of
      analgesic perioperatively. However, strong opioids, local anesthetics, and alpha
      2 agonists were underused, and there was an overreliance on weak opioids
      (butorphanol, meperidine). Up to 12% of veterinarians did not use any analgesics.
      Nationally, this may have affected many animals monthly; for example,
      approximately 6000 dogs or cats undergoing ovariohysterectomy. Continuing
      education (provincial level) and review articles were considered effective ways
      to inform veterinarians about optimal analgesic practices.

PMID- 16642875
TI  - Multifocal osteoma cutis in a golden retriever.
AB  - A 10-year-old, spayed female, obese golden retriever, presented for immune
      mediated thrombocytopenia, was successfully managed with the administration of
      vincristine and prednisone. However, 6 mo after discontinuing corticosteroid
      therapy because of suspected iatrogenic hyperglucocorticoidism, the patient was
      presented with multiple, firm, bilaterally symmetric, dermal masses composed
      histologically of differentiated cortical bone.

PMID- 16642876
TI  - Antifreeze ingestion by dogs and rats: influence of stimulus concentration.
AB  - Ingestive responses of 50 rats and 4 gastric-cannulated dogs to ethylene glycol
      based antifreeze (AF) were found to be inversely related to concentration. The
      antifreeze was never preferred to water. Do thirsty animals that encounter weak
      AF solutions drink them solely for their water content, water-related oral
      tactile sensations, or both, being inadvertently poisoned in the process?

PMID- 16642877
TI  - Mycoplasma mycoides subsp. capri associated with goat respiratory disease and
      high flock mortality.
AB  - A high mortality outbreak of respiratory mycoplasmosis occurred in goats in
      Mexico. The clinicopathologic presentation resembled contagious caprine
      pleuropneumonia caused by Mycoplasma capricolum subspecies capripneumoniae. By
      using a battery of polymerase chain reaction assays, the mycoplasma associated
      with this outbreak was identified as Mycoplasma mycoides subsp. capri.

PMID- 16642878
TI  - [Surgical resection of a gastrointestinal stromal cell tumor by double
      enterectomy and partial pancreatectomy on a 13-year-old mixed breed dog].
AB  - Surgical resection of a gastrointestinal stromal cell tumor by double enterectomy
      and partial pancreatectomy on a 13-year-old mixed breed dog. A 13 year-old, male,
      mixed breed dog, has been presented for an abdominal mass. The exam showed the
      presence of an ileo-caeco-colic mass adhered to the distal portion of the
      pancreas and the mid duodenum. A double enterectomy and a partial pancreatectomy
      were carried out and a diagnosis of gastrointestinal stromal cell tumor has been
      established.

PMID- 16642879
TI  - Bits and pieces.

PMID- 16642880
TI  - Problematic human-animal relationships: the animal-dependent client.

PMID- 16642881
TI  - Pulmonary thromboembolism.

PMID- 16642882
TI  - Outcome scoring system evaluation of knee osteoarthritis in patients awaiting
      TKA.
AB  - One hundred and twenty-four patients with knee osteoarthritis were reviewed at
      three stages over a mean of 24 months (range: 9-32 months) at the time of
      referral by the general practitioner, by the orthopedic consultant, and before
      surgery. At each visit, patients were examined and the American Knee Society
      score and Oxford Knee Society score were obtained. The functional element of the
      American Knee Score deteriorated significantly from the time of referral until
      the time of first orthopedic consultation (P=.005) and from the time of referral
      to the time of surgery (P=.006). The pain element of the American Knee Society
      score improved from the time of referral till the time of orthopedic assessment
      (P=.011). The change in Oxford Knee Society score between the time the patient
      was put on the waiting list to the time of surgery was not statistically
      significant (P=.30). This article questions the emphasis on surgical waiting
      times instead of symptoms and physical function in determining timing of surgery.

PMID- 16642883
TI  - Primary TKA with a zirconia ceramic femoral component.
AB  - This article presents the 2-year clinical results of primary total knee
      arthroplasty (TKA) performed with a zirconia ceramic femoral component. A
      posterior-stabilized TKA was performed for degenerative arthritis in 36 patients
      (39 knees). The components included a zirconia femoral component, a cobalt-chrome
      alloy tibial baseplate, and a polyethylene patella; all were implanted with bone
      cement. The ultra-high molecular-weight polyethylene-bearing insert had a deep
      dish, ultra-congruent design. At the 2-year interval, mean Western Ontario and
      McMaster Universities (WOMAC) osteoarthritis indices improved from 41 to 86, and
      mean Knee Society Scores improved from 40 to 92. Revision to constrained implants
      was necessary in one patient for persistent knee instability after trauma. These
      early results are encouraging, but more data are needed to determine whether
      ceramics are a suitable alternative to metal countersurfaces in TKAs.

PMID- 16642884
TI  - The stability of three commercially available implants used in medial opening
      wedge high tibial osteotomy.
AB  - This biomechanical study tested three commercially available fixation devices for
      medial opening wedge high tibial osteotomy (HTO). A medial opening wedge HTO
      model was created on replicate tibias. Fixation was achieved with one of three
      fixation devices: VS Osteotomy plate (EBI, Parsippany, NJ), Arthrex Osteotomy
      plate (Arthrex, Naples, Fla), and OsteoTrac plate (DJ Orthopedics Inc, Vista,
      Calif). For each fixation system, seven specimens were cyclically loaded in
      compression and torsion under physiologic loads on a servohydraulic machine. Mean
      axial stiffness was 2425 N/mm, 2358 N/mm and 2258 N/mm, respectively, for the
      EBI, Arthrex, and Alaron surgical plates. Mean torsional stiffness was 4.5
      Nm/degree, 4.1 Nm/degree and 4.0 Nm/degree, respectively, for the EBI, Arthrex,
      and DJ Orthopedics surgical plates. Though the differences are not statistically
      significant between the three fixation devices (P=.74 for mean axial stiffness
      and P=.10 for mean torsional stiffness), there is insufficient statistical power
      to rule out a true difference. Using this replicate tibia model, all three
      fixation devices tested appear to successfully stabilize the osteotomy site with
      regards to physiologic axial and torsional loads.

PMID- 16642885
TI  - Circular external fixation in knee arthrodesis following septic trauma sequelae:
      preliminary report.
AB  - Deep infection is one of the most devastating complications after knee fractures.
      It may be related to the initial fracture status or, more commonly, the surgical
      intervention. From 1991 to 2003, 12 patients underwent knee fusion to treat
      resistant infection after complex knee fractures or arthrodesis fractures using
      the Ilizarov method and frame. There were 9 men and 3 women (mean age, 39.7
      years). Two-thirds of the patients had long-standing infection and 5 patients had
      undergone earlier attempts at knee arthrodesis. Correction of concurrent
      malalignment was achieved in 2 patients. Bone transport using the same
      arthrodesis frame was necessary in 2 patients to overcome large bony defects.
      Solid fusion was achieved in all patients by the end of treatment. The average
      duration of external fixation was 22 weeks (range: 11-44 weeks). No patients
      required secondary bone grafting to achieve union. Complications occurred in 6
      (50%) patients. The most common problem seen was pin tract infection, but only 2
      patients required surgical intervention for its treatment. The study emphasizes
      the clinical success of the Ilizarov method in knee arthrodesis after infected
      fractures.

PMID- 16642886
TI  - Zolpidem reduces postoperative pain, fatigue, and narcotic consumption following
      knee arthroscopy: a prospective randomized placebo-controlled double-blinded
      study.
AB  - Sixty-eight patients undergoing outpatient knee arthroscopy for treatment of
      meniscal tears or loose bodies were divided into three treatment groups (zolpidem
      [24 patients], control [24 patients], and placebo [20 patients]). All groups
      received postoperative hydrocodone and ibuprofen. Patients in the zolpidem group
      received a single dose of zolpidem tartrate for the first seven postoperative
      nights. Patients in the placebo group received a gelatin capsule similar in
      appearance to zolpidem and patients in the control group received only
      hydrocodone and ibuprofen. Patients in the control group demonstrated
      significantly worse mean daily postoperative pain and more daily postoperative
      fatigue on visual analog scales when compared with the zolpidem group (P=.03 and
      P=.04, respectively). Patients in the placebo group had worse daily postoperative
      pain and more daily postoperative fatigue when compared to the zolpidem group,
      although these differences did not reach statistical significance (P=.15,
      power=0.6; and P=.27, power=0.48, respectively). Patients in the control group
      consumed significantly higher quantities of hydrocodone/acetaminophen
      postoperatively (P=.04) than patients in the zolpidem group. Finally, patients in
      the placebo group consumed higher quantities of hydrocodone/acetaminophen than
      the zolpidem group although the difference did not reach statistical significance
      (P=.4; power=0.15). Power was calculated for each insignificant relationship
      based on observed effect and sample sizes and variances. This study demonstrates
      that sleep and fatigue may be an important factor in the effective pain
      management following knee arthroscopy. Future postoperative treatment regimens
      should address sleep and fatigue to maximize analgesic effects in these patients.

PMID- 16642887
TI  - Patient-perceived outcomes and return to sport and work: TKA versus mini-incision
      unicompartmental knee arthroplasty.
AB  - Few reports have been published about patient-perceived outcomes and return to
      sport following total knee arthroplasty (TKA) compared with unicompartmental knee
      arthroplasty (UKA). This article compares the two procedures using self
      assessment questionnaires to determine whether there was a difference in patient
      perceived Oxford scores, return to sport, and return to work. Patient-perceived
      outcomes of mini-incision UKA (Oxford; Biomet Inc, Warsaw, Ind) and TKA were
      retrospectively reviewed at a minimum of 12 months after surgery. A total of 150
      patients underwent 183 UKAs (mean age: 71.5 years; standard deviation [SD]: 9.85)
      and 120 patients underwent 142 TKAs (mean age: 71.53 years; SD: 9.87). Oxford
      knee questionnaires were used assessing modified Grimby score, sports, and work
      activities. Mean Oxford knee score (22.17; SD: 9.03) for UKA was superior to TKA
      (24.5; SD: 9.68) (P=.04) scores. Mean modified Grimby score for UKA (3.89;
      SD:1.27) was superior to TKA (2.76; SD:1.12) (P<.0001). More patients returned to
      or increased sports following UKA (P=.0003), but no sooner than TKA patients.
      Patient-perceived Oxford and modified Grimby scores were better and sporting
      activity was greater following mini-incision UKA compared to TKA.

PMID- 16642888
TI  - Extraction of broken long intramedullary nails used in knee arthrodesis.

PMID- 16642889
TI  - Transient osteoporosis of the knee in pregnancy.

PMID- 16642890
TI  - Delayed diagnosis of a popliteal artery rupture after a posteromedial tibial
      plateau fracture-dislocation.

PMID- 16642891
TI  - Perioperative protocols for minimally invasive total knee arthroplasty.

PMID- 16642892
TI  - Anesthetic techniques for minimally invasive total knee arthroplasty.

PMID- 16642893
TI  - Postoperative pain management following total knee arthroplasty: a randomized
      comparison of continuous epidural versus femoral nerve infusion.

PMID- 16642894
TI  - Minimally invasive quadriceps-sparing TKA: results of a comprehensive pathway for
      outpatient TKA.

PMID- 16642895
TI  - The economics of minimally invasive total knee arthroplasty.

PMID- 16642896
TI  - EDs slash unnecessary visits using interfaced computers, common protocols.
AB  - Foundation funding and teamwork with your competitors can be a powerful
      combination: Three Lincoln, NE-based EDs have cut unnecessary visits by two
      thirds. Interface your computer systems so that all participating EDs have common
      information about the targeted patient population. Involve your information
      technology and privacy experts from day one of the program. Implement case
      management for consistent treatment of patients and to serve as liaison with
      primary care providers.

PMID- 16642897
TI  - New coma scale offers option to Glasgow.
AB  - A new coma scale called the FOUR Score may provide ED managers with an
      alternative to the Glasgow Coma Scale. Here are some of the advantages it offers:
      the ability to test brainstem reflexes to obtain a clearer picture of
      neurological status, according to the scale's developer; greater simplicity. In
      the new scale, every component has a maximal score of 4. In the Glasgow Coma
      Scale, the maximal number varies with each component; the ability to learn more
      about the condition of intubated patients than you can with the Glasgow Coma
      Scale.

PMID- 16642898
TI  - Diversions worsening, trend may continue.
AB  - Operational changes and viewing the issue from a hospital-wide perspective are
      keys to internal flow improvements. Develop a greater knowledge of, and embrace
      implementation of, evidence-based operations. Actively advocate that hospital
      leadership become engaged in improving real-time management of flow. Learn to
      recognize the major barriers to flow within the hospital, such as the OR's
      elective admission schedule.

PMID- 16642899
TI  - Study: children may get antibiotics too often.
AB  - Unnecessary use of antibiotics can endanger patients, increase bacteria
      resistance, and result in added expenditures. There are only four appropriate
      medications that should be given to children in whom strep is suspected. You may
      wish to consider giving Group A beta-hemolytic streptococcus test to children
      before prescribing an antiobiotic. Staff also should take into consideration
      whether the patient has been exposed to friends or relatives with strep.

PMID- 16642900
TI  - Sinus graft with biogran, autogenous bone, and PRP: a report of three cases with
      histology and micro-CT.
AB  - Three sinuses were grafted with a bioactive glass bone substitute (Biogran) mixed
      with autogenous bone retrieved from intraoral donor sites. In two of the three
      sinuses a platelet-rich plasma (PRP) gel was added to the graft. Bone biopsies
      retrieved after 5, 6, and 15 months were analyzed. Micro-computerized tomography
      (micro-CT) values of total bone volume/total volume (TBV/TV) were very reliable
      compared to histomorphometry. Biogran mixed with autogenous bone and PRP seems to
      have a positive effect in sinus grafting, with TBV/TV values ranging between 40%
      and 68%. Micro-CT results have never been compared with histomorphometry for the
      evaluation of grafted biomaterials. Micro-CT evaluation of some morphometric
      parameters was difficult, because the radiodensities of Biogran and a certain
      grade of bone mineralization were similar.

PMID- 16642901
TI  - Comparison of recombinant human platelet-derived growth factor-BB plus beta
      tricalcium phosphate and a collagen membrane to subepithelial connective tissue
      grafting for the treatment of recession defects: a case series.
AB  - When mixed with an osteoconductive scaffold, recombinant human platelet-derived
      growth factor (rhPDGF-BB), a potent wound-healing protein, has been shown to
      promote clinical attachment gain, radiographic bone fill, and regeneration of the
      periodontium. This human case series evaluated the clinical outcome of rhPDGF
      with beta tricalcium phosphate (3-TCP) and a collagen membrane in the treatment
      of recession-type defects. The control was the clinical gold standard for root
      coverage: the subepithelial connective tissue graft (CTG). Seven patients with
      recession defects > or = 3 mm in contralateral quadrants of the maxilla,
      excluding molars, were treated in this series. Patients were followed
      postoperatively, and healing was evaluated at 8, 16, and 24 weeks, with recession
      depth as the primary outcome measure. This case series revealed a favorable
      tissue response to rhPDGF-BB + beta-TCP and a collagen membrane and comparable
      clinical outcomes to CTG, warranting a controlled clinical trial of greater
      magnitude.

PMID- 16642902
TI  - Immunohistochemical evaluation of inflammatory mediators in failing implants.
AB  - It was hypothesized that peri-implant tissue around loosening dental implants may
      contain cytokines with a potential to regulate osteoclasts. Peri-implant and/or
      gingival samples from loosened implants, chronic periodontitis (CP), and normal
      controls (n = 10 samples in each group) were analyzed using immunohistochemical
      staining to observe tumor necrosis factor alpha (TNF-alpha), interleukin 1-alpha
      (IL-1alpha), IL-6, platelet-derived growth factor A (PDGF-A), and transforming
      growth factor alpha (TGF-alpha). These cytokines were found in foreign-body giant
      cells, macrophages, fibroblasts, and epithelial cells. TNF-alpha, IL-1alpha, and
      IL-6 were increased (P < .05; unpaired t test) in peri-implantitis and CP,
      whereas PDGF-A and TGF-alpha were not. In conclusion, cytokines with a potential
      to activate osteoclasts were found in both peri-implantitis and CP, but the
      cytokine profiles differed in that IL-1alpha was the most prevalent cytokine in
      the former and TNF-alpha was the most common in the latter. These cytokines may
      contribute to peri-implant bone loss/loosening by stimulating formation and
      activity of osteoclasts and might be an amenable target for local therapies with
      cytokine modulators.

PMID- 16642903
TI  - Effect of design of all-ceramic resin-bonded fixed partial dentures on clinical
      survival rate.
AB  - In the treatment of single-tooth gaps, the resin-bonded fixed partial denture
      (FPD) has established itself as an alternative treatment modality. With the
      advent of high-strength ceramics, such as aluminum oxide ceramics, it appeared to
      be possible to fabricate all-ceramic resin-bonded FPDs without a metal
      reinforcement. However, fractures of the traditional two-retainer design of these
      restorations occurred quite frequently. It was proposed to change the two
      retainer design to a single-retainer design with the hope that the survival rate
      could be improved. Nevertheless, the use of aluminum oxide ceramics can be
      problematic. The present study strongly suggests that the clinical performance of
      resin-bonded FPDs made of a high-strength glass-ceramic is in large measure
      dependent on their design.

PMID- 16642904
TI  - Transcrestal sinus floor elevation: report of a case series.
AB  - The technique of the osteotome-mediated transcrestal sinus floor elevation is
      described in a series of case reports. Fifty-five patients received a total of 66
      implants over a period of 6 years. Bio-Oss was added in more than 60% of cases to
      increase the stability of the lifted area. The surgical procedure appeared to be
      a safe method that was well supported by the patients. It was applied for
      different prosthetic indications in partially and completely edentulous
      situations. The survival rate of the implants during the healing phase was 98.5%,
      and it was 100% after loading. The patients' responses to the Summers technique
      were evaluated by means of short interviews and visual analog scales (VAS), and
      the answers were compared with those from a group of patients who had received
      implants in the same location during the same period but without the osteotome
      technique. The answers regarding pain were not different between the groups.
      However, significantly more patients who had received the implants by means of
      the osteotome technique judged the surgical procedure as highly uncomfortable. It
      is concluded that patients need to be well prepared for the procedure.

PMID- 16642905
TI  - Effects of combined treatment with porous bovine inorganic bone grafts and
      bilayer porcine collagen membrane on refractory one-wall intrabony defects.
AB  - The aim of this study was to investigate the effects of a combination of porous
      bovine inorganic bone graft (Bio-Oss) and bilayer porcine collagen membrane (Bio
      Gide) on refractory one-wall intrabony defects in dogs. Bio-Oss and Bio-Gide were
      applied into the refractory one-wall intrabony defect. The contralateral sites
      were used as controls (without the application of Bio-Oss and Bio-Gide). At 24
      weeks after surgery, similar pocket depths were found in both groups. However,
      histologic observation revealed an infiltration of inflammatory cells in the
      control group caused by poor gingival architecture, whereas only a few of the
      experimental sites showed inflammatory infiltration. In addition to the healthy
      gingival tissue, periodontal tissue regeneration was observed in the experimental
      group. The combination of Bio-Oss and Bio-Gide was an effective treatment for
      refractory one-wall intrabony defects in dogs.

PMID- 16642906
TI  - Minimally invasive extraction and immediate implant placement: the preservation
      of esthetics.
AB  - Extraction sites in the esthetic zone present an obvious restorative challenge.
      This case report describes a surgical technique for the preservation of anterior
      esthetics that combines minimally invasive extraction with immediate implant
      placement. This single-stage approach preserves site morphology by protecting and
      supporting existing hard and soft tissues. Clinical success appears to be
      attributable to several important features of the technique. The first step
      involves the elevation, luxation, and extraction of the tooth using either a
      flapless or minimally invasive approach that reduces trauma to the adjacent
      tissues. The second step involves appropriate orientation, placement, and
      stabilization of the implant to preserve facial bone and soft tissue contours.
      Implant placement is accomplished using particulate freeze-dried bone allograft
      and enamel matrix derivative to achieve ridge preservation and bone augmentation.
      The composite graft material is considered critical for predictably resolving
      osseous voids and promoting implant integration, and consideration is given to
      the concept of osteogenic "jumping distance" between the implant and the
      eccentric walls of the alveolus. Finally, preservation of the soft tissue
      architecture during wound healing is achieved by placement of either a fixed or
      removable restoration. Consistent implant integration and preservation of the
      hard and soft tissue complexes have been achieved using this approach.

PMID- 16642907
TI  - Compressive shear bond strength of core buildup materials.
AB  - New tooth-colored restorative materials have been developed with the goal of
      replacing amalgam. These restoratives are marketed as packable composite and
      ormocer. The purpose of the present study was to compare the compressive shear
      bond strengths of these new materials with that of hybrid composite and amalgam
      as core materials. Standardized core buildups were made on four groups of
      extracted molars, with 10 teeth per group. Three tooth-colored restorative
      materials (Filtek Z 250, Filtek P 60, and Definite) and an amalgam (SDI Permite)
      were used. Specimens were placed in a special jig at a 45-degree angle. The
      compressive shear bond strength was obtained using a universal testing machine.
      The Kruskal-Wallis test was used to compare the groups, and pairwise comparisons
      were made by Mann-Whitney U test (P < .05). Filtek P 60, a packable composite
      resin, had the greatest compressive shear bond strength values in all instances,
      and the ormocer (Definite) had the lowest. The strengths of packable composite,
      hybrid composite, and amalgam as core materials were not significantly different
      (P > .05).

PMID- 16642908
TI  - Molecular changes in the gingival epithelium associated with necrotizing
      ulcerative periodontitis: a case report.
AB  - A case of necrotizing ulcerative periodontitis (NUP), the most severe
      inflammatory periodontal disorder caused by plaque bacteria, is shown.
      Clinically, the gingiva showed distinct signs of ulceration, and radiography
      revealed horizontal bone loss. Indirect immunofluorescence, carried out on frozen
      sections of tissue specimens obtained from the NUP lesion, exhibited clear
      expression of atypical keratin K19, particularly in basal cells, when compared to
      noninflamed gingiva. Moreover, NUP tissue showed extensive intraepithelial
      abundance for the basement membrane component laminin-1/10 and the extracellular
      matrix molecule tenascin. Strong expression of integrin subunit alphav and matrix
      metalloproteinase-13 in conjunction with interleukin 1-beta further discriminated
      NUP gingival epithelium from normal tissue. The results suggest that NUP is
      associated with changes in the expression and topography of the analyzed
      molecules in the gingival epithelium, which in turn may reflect the fast
      progression of the disease.

PMID- 16642909
TI  - Cultural specificity and universality of suicide: challenges for the
      International Association for Suicide Prevention.

PMID- 16642910
TI  - Definitions of suicidal behavior: lessons learned from the WHo/EURO multicentre
      Study.
AB  - Based on the experience matured during the 15 years of the WHO/EURO Multicentre
      Study on Suicidal Behavior, this paper provides an excursus on main elements that
      characterize components for definitional needs. It describes the rationale for
      choosing the initial set of definitions within the study and the subsequent
      problems and developments. As a result, unifying terminologies are proposed.

PMID- 16642911
TI  - Suicidal behavior by burns among adolescents in Kurdistan, Iran: a social
      tragedy.
AB  - The aim of this study was to identify the epidemiologic features and current
      etiological factors of suicidal behavior by burns among adolescents in Kurdistan,
      Iran. A prospective population-based study was carried out on patients with
      suicidal behaviors by burns requiring hospitalization among adolescents during
      2000-2001 in Kurdistan, Iran. Sociodemographic and etiological factors were
      obtained through interviews with each patient or with family, relatives, or
      friends of the patient. Of 54 hospitalized burn patients aged 13-19 years, 40
      (74.1%) patients were hospitalized because of suicidal behaviors by burns (6
      males and 34 females). The incidence rate of these behaviors was 18.1 per 100,000
      person-years (P-Y) and varied by gender (the incidence rates for females and
      males were 31.6 and 5.3 per 100,000 P-Y, respectively, p(2) = .000004). Most of
      the patients (60%) were single, 70% were homemakers, and 60% were either
      illiterate or had a low level of education. The most common precipitating factors
      for suicidal behaviors by burns were a quarrel with a family member or relative
      (47.5%) and marital conflict (17.5%). Most of the patients who were able to
      communicate regretted their suicidal behaviors (85.7%). Adolescents in Kurdistan
      are at higher risk of suicidal behaviors by burns compared to adolescents in
      other areas of Iran. Factors likely to be associated with suicidal behaviors by
      burns include lower socioeconomic status and family problems. These factors
      should be investigated further to better elucidate the etiology of these events.
      It also is necessary to implement prevention programs and strategies known to be
      effective to reduce the incidence of suicide in this region.

PMID- 16642912
TI  - Suicide to harass others: clues from mythology to understanding suicide bombing
      attacks.
AB  - Suicide by revenge, the Samsonic suicide, and the suicide by devotio, all
      described in classical mythology and also reported in the ethnographic
      literature, belong to the same class of suicidal behaviors as kamikaze suicide
      and the suicide bombing attack: suicide to harass and burden others or suicide
      with a hostile intent. The lack of a social dimension to share in a positive
      manner may lead an individual to integrate him/herself in another social
      structure, e.g., a military organization, which allows the individual to express
      his/her desires and personal identity only by destroying others and themselves.
      The dynamics of these forms of suicide are also likely to work in other displays
      of life-threatening behavior, such as family annihilation, mass murder, and spree
      killing. A more thorough investigation of the dynamics operating in suicide
      bombing attacks could, therefore, contribute to preventative strategies against
      violence at large.

PMID- 16642913
TI  - Fragmented pathways to care: the experiences of suicidal men.
AB  - Using qualitative methods, this study examined how, and under what circumstances,
      suicidal men used mental health services. In particular, the analyses focused on
      fragmented pathways to care. Fifteen men with a history of suicidal and
      aggressive behaviors and a diagnosis of borderline personality disorder and/or
      antisocial personality disorder participated in semistructured interviews that
      consisted of questions about their mental health status and experiences with
      mental health and addiction services. Interviews were taped and transcribed. An
      iterative, inductive qualitative analytic process was used. Men followed a
      cyclical pattern wherein negative experiences with health care providers were
      said to be followed by avoidance of health care settings, crisis, and then by
      involuntary service utilization. Men identified five health care provider and
      three personal practices, and two types of episodes they believed to contribute
      to their fragmented pathways to care. Implementation of specialized
      interventions, and providing patients with more information and more opportunity
      to participate in decisions, may improve interactions between patients and
      providers and improve patients' mental health status.

PMID- 16642914
TI  - SOPRoxi: a research-intervention project for suicide survivors.
AB  - In Italy, postvention models specifically designed for people surviving the
      suicide of a loved one are very scarce. The SOPRoxi project was developed to
      respond to this particular lack. By involving different professional and
      nonprofessional figures (GPs, mental health professionals, social workers,
      volunteers, etc), the SOPRoxi project aims to remove the stigma associated with
      this condition and to offer adequate, multifaceted help to survivors.

PMID- 16642915
TI  - Crisis intervention after the Tsunami in Phuket and Khao Lak.
AB  - After the Tsunami disaster in Southeast Asia, India, Sri Lanka, and Africa, the
      German government set up a crisis task force that implemented crisis-intervention
      teams covering Thailand (Phuket and Khao Lak), Sri Lanka, and Sumatra. Two crisis
      teams were sent to Phuket; the first one on 28 December 2004, and the second one
      on 3 January 2005, each for an average of 1 week. This intervention was primarily
      for the benefit of German citizens and their expatriates and relatives caught up
      in a major catastrophe as well as the German helpers. This article describes the
      organizational structures of the German crisis intervention, protective factors
      for the helpers, psychiatric syndromes--often acute traumata, the problems of the
      identification process for relatives, and crisis intervention itself.
      Consequences for further crisis intervention after natural disasters are
      discussed.

PMID- 16642916
TI  - Social integration and suicide in South Korea.
AB  - The increasing suicide rate in South Korea in recent decades was found to be
      associated with measures of social integration/regulation (birth and divorce
      rates).

PMID- 16642917
TI  - The Ringel Service Award: the man.

PMID- 16642918
TI  - Japan's first open-heart surgery with pump oxygenator.

PMID- 16642919
TI  - Impact of concomitant cardiac procedure on coronary artery surgery in
      hemodialysis-dependent patients.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) in hemodialysis-dependent
      patients is associated with high mortality and morbidity rates. This
      retrospective study was undertaken to identify the risk factors for in-hospital
      mortality for hemodialysis-dependent patients. METHODS: Subjects included 87
      consecutive hemodialysis-dependent patients (81 men and 6 women), aged 47-82
      years (mean age, 65 years), who underwent CABG. Operative procedures included
      CABG alone (n=77) and CABG with valve replacement, repair, or the Dor procedure
      (n=10). Thirty-one perioperative risk factors were subjected to univariate and
      multivariate analyses to identify the risk factors for hospital death. RESULTS:
      The overall in-hospital mortality rate, including operative death, was 14.9%
      (13/87). Univariate analysis showed the following 7 risk factors to be
      statistically significant predictors of hospital death: age > or = 70 years, a
      concomitant cardiac procedure, left ventricular ejection fraction <30%, left
      ventricular end-systolic volume index >70 ml/m2, a left main lesion,
      emergency/urgent surgery, and anemia (hemoglobin <10 mg/dl) (p<0.05 for each
      predictor). Multivariate logistic regression analysis confirmed that a
      concomitant cardiac procedure (chi-squared = 17.080, p=0.013) and age > or = 70
      years (chi-squared = 9.112, p=0.019) are statistically significant independent
      risk factors for hospital death. CONCLUSION: A concomitant cardiac procedure and
      age > or = 70 years were identified as significant independent risk factors for
      hospital mortality after CABG for hemodialysis-dependent patients. These
      preoperative risk factors may help in predicting operative risks and improving
      clinical outcomes in hemodialysis-dependent patients undergoing CABG.

PMID- 16642920
TI  - Prostaglandin E1 attenuates impairment of cellular immunity after cardiopulmonary
      bypass.
AB  - OBJECTIVE: It is well documented that cardiopulmonary bypass (CPB) severely
      impairs cellular immunity. The objective of this study was to investigate the
      effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS:
      Patients who underwent elective cardiac surgery were randomly divided into the
      PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was
      administered at 20 ng/kg/min from just after the induction of anesthesia to the
      end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before
      anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7).
      Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein
      derivative (PPD) antigen were measured as indicators of cellular immunity.
      RESULTS: PGE1 significantly attenuated the impairment of both PHA and PPD
      response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%,
      control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs.
      PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was
      significantly decreased on POD 1. CONCLUSION: PGE1 attenuated the impairment of
      cellular immunity after cardiac surgery with CPB by reducing oxidative stress on
      PBMCs.

PMID- 16642921
TI  - Aortic operation after previous coronary artery bypass grafting: management of
      patent grafts for myocardial protection.
AB  - OBJECTIVES: Aortic surgery for progressive aortic valve disease or aortic
      aneurysm after previous coronary artery bypass grafting (CABG) is a challenging
      procedure. We report the outcome of aortic reoperation after previous CABG and
      evaluate our management of patent grafts and our methods for obtaining myocardial
      protection. METHODS: From February 2001 to July 2003, 6 patients with progressive
      aortic valve disease and aneurysm of the thoracic aorta were operated on. The
      group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4
      patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic
      dissection, and 1 with progressive aortic valve stenosis. The interval between
      previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were
      performed via median resternotomy. Myocardial protection was obtained by
      hypothermic perfusion of patent in-situ arterial grafts following cold-blood
      cardioplegia administration via the aortic root under aortic cross clamping.
      RESULTS: The operative procedure was aortic arch replacement in 4 patients,
      ascending aortic replacement with double CABG in 1, and aortic valve replacement
      in 1. All patients survived the reoperation. Postoperative maximum creatine
      kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram
      nor were any new wall motion abnormalities recognized on echocardiography. There
      were no late deaths during a follow-up of 30.7 months. CONCLUSION: Reoperative
      aortic procedures after CABG can be performed safely with myocardial protection
      via hypothermic perfusion of a patent in-situ arterial graft.

PMID- 16642922
TI  - Mycotic aneurysm of the distal aortic arch caused by Aspergillus.
AB  - We describe an unusual case of a thoracic aortic aneurysm caused by Aspergillus.
      A 70-year-old man underwent prednisolone and Ara-C treatments for a
      myelodysplastic syndrome. Blood examination revealed pancytopenia. Under these
      treatments, an aneurysm presented at the distal aortic arch. He underwent
      resection of the aneurysm with a graft repair covered by a pedicled omentum flap,
      followed by prolonged administration of micafungin and itraconazole for a mycotic
      aneurysm. The postoperative course was favorable without complications. Serum C
      reactive protein became negative and he was discharged 2 months after the
      surgery. However, 4 months after the surgery, he died from worsening of the
      myelodysplastic syndrome. The prognosis for patients with mycotic aneurysms is
      poor due to their immunocompetent condition arising from underlying diseases.
      Therefore, in addition to prompt treatment with antifungal agents combined with
      surgical debridement, control of the underlying disease is essential for
      improving the outcome.

PMID- 16642923
TI  - Surgical treatment for thoracic aortic aneurysm with aberrant right subclavian
      artery.
AB  - We present two operative cases of thoracic aortic aneurysm combined with aberrant
      right subclavian artery (ARSA). Case 1 was a 71-year-old man with a fusiform-type
      arch aneurysm. He underwent total aortic arch replacement to reconstruct all 4
      arch branches. Case 2 was a 39-year-old man suffering from chronic DeBakey type
      IIIb dissection. He underwent total descending thoracic aortic replacement for
      the remaining ARSA. In both cases ARSA was diagnosed preoperatively by
      reconstructed three-dimensional computed tomography (3D-CT). Both patients
      followed uneventful postoperative courses with excellent results. 3D-CT is
      helpful for precise planning of surgical strategy in such cases.

PMID- 16642924
TI  - Successful treatment of intracardiac progression and metachronous multiple brain
      metastases from primary lung cancer.
AB  - We report a rare case of squamous cell carcinoma of the lung extending into the
      left atrium via the pulmonary vein. The tumor tissue including the thrombus was
      resected en-bloc under cardiopulmonary bypass. Despite adjuvant chemotherapy,
      multiple brain metastases developed, but they were eradicated by stereotactic
      radiosurgery. The patient is still disease-free 48 months after the resection.
      This case serves to demonstrate the validity of multidisciplinary treatment for
      locally advanced lung cancer.

PMID- 16642925
TI  - Resected invasive thymoma with multiple endocrine neoplasia type 1.
AB  - We report a rare case of multiple endocrine neoplasia (MEN) type 1 with thymoma.
      A 57-year-old woman with a chronic duodenal ulcer and hypoglycemia had been seen
      at a nearby clinic. Abdominal echogram revealed two nodules in the pancreas and
      she was referred to our hospital for evaluation. Her diagnosis was MEN type 1,
      gastrinoma and hyperparathyroidism with anterior mediastinal tumor. There were
      high calcium levels in the blood and urine. Gastrin was quite high. A chest X-ray
      revealed a retrosternal tumor. Computed tomography revealed an anterior
      mediastinal tumor without sign of invasion to the surrounding organs, and two
      small masses in the pancreas. Cervical echogram revealed a few masses in both
      sides behind the thyroid. From these findings, her preoperative diagnosis was MEN
      type 1 with thymic carcinoid or thymoma. We performed thymectomy and
      parathyroidectomy concomitantly. The mediastinal tumor was diagnosed as invasive
      thymoma.

PMID- 16642926
TI  - Large cell neuroendocrine carcinoma of the lung with a cystic appearance on
      computed tomography.
AB  - Almost all reported cases of large cell neuroendocrine carcinoma (LCNEC) of the
      lung are solid-type tumors. We encountered a rare case of LCNEC displaying a
      cystic shape. An abnormal cystic shadow was revealed on chest computed tomography
      in a 71-year-old man who underwent total gastrectomy due to gastric cancer 5
      years earlier. The cystic lesion enlarged from 7 mm to 16 mm over 7 months, so
      surgery was performed for definitive diagnosis and therapy. Microscopy revealed
      rosette patterns, a high mitotic rate and a large area of necrosis.
      Neuroendocrine differentiation was confirmed on immunohistochemical examinations
      using chromogranin, synaptophysin and NCAM (CD56). Given these findings, LCNEC
      was diagnosed. This is the first report of LCNEC with a cystic shape. This case
      challenges preconceptions regarding the radiographic appearance of LCNEC.

PMID- 16642927
TI  - Saphenous vein graft rupture eighteen years after coronary artery bypass
      grafting.
AB  - Delayed saphenous vein graft (SVG) rupture following coronary artery bypass graft
      (CABG) is an unusual but potentially fatal complication. Herein we report a case
      of SVG rupture 18 years after CABG. A 75-year-old man had undergone a CABG with
      SVG in 1987 at another institution. In 2004 the patient developed angina and
      underwent re-CABG with arterial conduits in our hospital. On the preoperative
      cineangiogram, the SVG to the right coronary artery (RCA) was irregularly
      dilated, yet still providing flow to the distal RCA. In 2005 he was readmitted to
      our hospital for abdominal pain. Chest computed tomography revealed a huge round
      mass adjacent to the heart. Cineangiogram showed leakage of the contrast in the
      midportion of the SVG. At operation, graft rupture was evident and repaired under
      cardiopulmonary bypass. Although cardiac function was well maintained, after the
      surgery he developed ischemic colitis and died of multiple organ failure on the
      17th postoperative day.

PMID- 16642928
TI  - Ascending aortic aneurysm following aortico-ventricular tunnel repair.
AB  - Aortico-left ventricular tunnel is a very rare congenital anomaly. An 18-year-old
      boy had undergone tunnel closure at 3 years of age. A moderate degree of aortic
      regurgitation remained postoperatively. Seven years later, aortic valve
      replacement for aortic regurgitation was performed. Eight years later, the
      ascending aortic aneurysm had grown to 63 mm in diameter. This dilatation became
      an operative indication. Ascending aortic replacement was performed with a Dacron
      graft. Pathological examination of the resected aortic wall revealed cystic
      medial degeneration. We report a rare case of ascending aortic aneurysm following
      surgical repair of the aortico-left ventricular tunnel and aortic valve
      replacement.

PMID- 16642929
TI  - [The most probable clinical diagnosis to the applicants for the intractable
      disease registration of Parkinson's disease, spinocerebellar degeneration and
      amyotrophic lateral sclerosis].
AB  - Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and spinocerebellar
      degeneration (SCD) are included in the 45 intractable diseases" acknowledged by
      the Ministry of Health, Labour and Welfare of Japan. The registration of
      applicants is based on the attending doctors' diagnosis, and medical costs of
      registered patients are covered by the government. However, the accuracy of the
      diagnoses has not been investigated previously. The aim of the present study is
      to investigate the accuracy of the diagnoses of patients registered as PD, SCD
      and ALS in Mie prefecture of Japan. The study design was cross-sectional and the
      survey was carried out using an anonymous questionnaire. We asked the attending
      doctors the most probable clinical diagnosis in each applicant for PD, SCD or ALS
      at the annual renewal of application form of the specified diseases by the
      Ministry. The questionnaires were sent to the 57 neurologists in 20 general
      hospitals and 2 neurology clinics in Mie prefecture, Japan. The survey was
      carried out from July to September, 2003. For each disorder (PD, ALS, SCD), the
      accuracy rates were calculated as the ratio of the number of patients with the
      most probable diagnosis of the consistent disease to the number of all patients
      registered each disease. Questionnaires on 678 patients replied from 31
      neurologists, 27 of whom were the neurology specialists approved by the Japanese
      Society of Neurology, were retrieved and analyzed. They covered 41.1% of the
      total registered PD cases, 45.4% of total SCD cases, and 54.0% of total ALS cases
      in Mie prefecture. The final clinical diagnosis were made by such specialists in
      641 cases (94.5%). The accuracy rate of PD was 97.3% for all degenerative
      parkinsonisms and 90.2% for idiopathic PD, 96.0% for SCD, and 77.8% for typical
      ALS and 81.5% for ALS and Kennedy-Alter-Sung syndrome. Although the most probable
      diagnoses were performed by the attending physicians without verification by
      other raters, the accuracy rates were excellently high in these diseases, partly
      because most of the attending physicians were neurology specialists. The
      relatively low accuracy rate in ALS may be caused partly by the difficulty in
      differentiating it from spine diseases, neuropathies or myopathies at the early
      stage of the disease when the patients had been registered, or by inclusion of
      other motor neuron diseases such as Kennedy-Alter-Sung syndrome.

PMID- 16642930
TI  - [A 62-year-old woman with early-onset Parkinson's disease associated with the
      PINKi gene deletion].
AB  - We report the first case of early-onset Parkinson's disease (EOP) with the PTEN
      induced kinase 1 (PINK1) gene deletion in 62 years old Japanese female. The
      symptoms were started with unstable gait at the age 38. Parkinsonian symptoms
      became apparent in 45 years old. L-Dopa was markedly effective on her
      parkinsonian symptoms. However, equinovarus foot induced by L-Dopa intake
      appeared three months prior to the admission. On admission, she presented with
      mild cognitive impairment, severe depression, marked retropulsion, resting tremor
      in the left upper limb and mild hyperreflexia in the four limbs. Rigidity was not
      present. Mutational analysis revealed homozygous deletion from exon 6 to 8 in the
      PINK1 gene. An ethnic diversity in PINK1 mutation is suggested.

PMID- 16642931
TI  - [Chronic inflammatory demyelinating polyneuropathy followed by systemic lupus
      erythematosus and Sjogren syndrome: a case report].
AB  - We report a 60-year-old man with chronic inflammatory demyelinating
      polyneuropathy (CIDP) accompanying systemic lupus erythematosus (SLE) and Sjogren
      syndrome (SS). He was admitted to our hospital because of progressive weakness
      and dysesthesia in the distal parts of the bilateral upper and lower extremities.
      We diagnosed the illness as CIDP and treated him with steroids, plasma filtration
      and high-dose intravenous immunoglobulin therapy (IvIg). Consequently, his
      symptoms improved gradually and he was discharged. However, 2 years after the
      first admission, he experienced dyspnea on effort and chest X-ray demonstrated
      right pleural effusion. Consequently, he gradually developed gait disturbance,
      loss of taste, and severe dysesthesia in his lower limbs. Therefore, he was
      admitted again. On neurological examination, mild weakness was detected in all
      limbs distally. Deep tendon reflexes were absent. The sensation of position and
      vibration was diminished in the fingers and toes. He could not walk by himself
      and demonstrated an ataxic gait with a wide base. Examination of cranial nerves
      demonstrated no abnormalities, except for loss of taste. Serological examination
      demonstrated positive auto-antibodies including antinuclear, anti-DNA, and anti
      SS-A antibodies. Urinalyses showed albuminuria and microscopic hematuria.
      Cerebrospinal fluid (CSF) was clear and colorless, containing 3 mononuclear cells
      per cubic mm, with a protein of 275 mg/dl. Magnetic resonance images (MRIs) of
      the brain and entire spine were normal. Neurophysiological studies demonstrated
      an absence of sensory nerve action potentials in the right arm and markedly slow
      conduction velocities, conduction block in the ulnar forearm segment and absence
      of F waves in all limbs. The renal biopsy revealed lupus nephritis. The lip
      biopsy demonstrated chronic sialoadenitis consistent with SS, altough patient did
      not show symptoms of arthritis or vasculitis. It is well known that mononeuritis
      multiplex and acute demyelinating polyneuropathy accompany SLE. However there are
      few reports that describe the occurrence of CIDP in patients with SLE, and the
      association of "CIDP-like" neuropathy in patients with SS. Our case suggests that
      the autoimmune disease associated with SLE and SS may induce "CIDP-like"
      inflammatory demyelinating polyneuropathy.

PMID- 16642932
TI  - [A case of dermatomyositis associated with chronic idiopathic myelofibrosis].
AB  - A 74-year old woman had been suffering from chronic idiopathic myelofibrosis
      (CIMF) for three years before noticing skin rash and subsequent muscle weakness.
      On admission, purplish and erythematous skin rash was seen spreading over large
      parts of her body, including the face, chest, back and extremities. She could not
      stand up without assistance due to weakness. On laboratory examination, her
      hemoglobin was found to be 11.8g/dl, platelet 17,000/microl, WBC 22,500/microl
      (with blast cells), and CK 1,757 IU/I. Auto-antibodies including antinuclear
      antibody, Jo-I antibody and rheumatoid factors were negative. Abdominal CT
      revealed giant splenomegaly. She was diagnosed as having dermatomyositis (DM)
      associated with CIMF. Although administration of prednisolone followed by methyl
      prednisolone pulse therapy ameliorated the weakness and skin rash, WBC increased
      to 35,000/ microl. In case of worsening of CIMF, azathioprine (AZP) administered.
      This decreased the WBC count to 13,700/microl and the CK to 49 IU/I 40 days after
      the administration. Patients with CIMF have an increased incidence of
      complications of other autoimmune diseases, indicating that the immunological
      mechanism plays some roles in the progression of the disease. There has been only
      one other reported case of DM complication. This case suggests usefulness of AZP
      treatment combined with prednisolone in these patients.

PMID- 16642933
TI  - [Seizure-induced transient brain edema in the medial temporal lobe].
AB  - We reported a patient with sudden onset seizure resulting in prolonged amnesia.
      MRI revealed a T2 high signal lesion with swelling in the right medial temporal
      lobe. Because the MRI lesion remained to be the same in size for two months,
      biopsy specimens were obtained under informed consent to rule out the brain
      tumor. Based on histological findings showing brain edema without specific
      abnormal findings (malignancy, inflammation etc), we concluded that the temporal
      lesion was the edema induced by the seizure attack. In Japan, many papers on non
      herpetic acute limbic encephalitis (NHALE) have recently been published. In their
      reports, seizures were frequently observed as a preceding symptom; moreover,
      clinical courses and MRI findings are similar to those of seizure-induced brain
      edema. The secondary brain edema induced by the seizure must be considered in
      patients with NHALE and other CNS disorders, especially if the patient has a
      history of the recent seizure.

PMID- 16642934
TI  - [A case of autoimmune autonomic neuropathy with marked orthostatic hypotension,
      decreased salivation, constipation, and Adie pupil].
AB  - We report a 68-year-old man with subacute autonomic failure who developed
      orthostatic hypotension, decreased salivation, constipation, and Adie pupil.
      There was no evidence of central neurodegeneration, sensory and motor
      dysfunction. Head-up tilt test showed marked orthostatic hypotension without
      tachycardia. The patient had a low plasma noradrenaline concentration while
      supine and a poor noradrenaline response to head-up. Adie pupil responded to
      0.125% pilocarpine, establishing denervation hypersensitivity of the
      parasympathetic nerve. Blood pressure, However, did not show a remarkable
      response to 0.05-0.2gamma noradrenaline, demonstrating the absence of denervation
      hypersensitivity of the sympathetic nerve. In contrast to patients with pure
      autonomic failure, the patient showed normal uptake of I-123-MIBG in the
      myocardium, indicating intact postganglionic sympathetic innervation. Serologic
      testing demonstrated circulating antibody to the ganglionic acetylcholine
      receptor (AchR). Because of subacute clinical course, autonomic symptoms and
      presence of anti-ganglionic AchR antibody, autoimmune autonomic neuropathy was
      diagnosed.

PMID- 16642935
TI  - [Cerebellar infarction restricted to bilateral inferior vermis presenting with
      floating sensation and then astasia].
AB  - A 76-year-old man suddenly experienced floating sensation, transient vertigo, and
      nausea. Neurological examination was unremarkable except for hypotonia and mild
      ataxia in the limbs, but orthostatic nausea and vomiting forced him to take a
      quiet, recumbent position. Magnetic resonance imaging of the brain showed
      cerebellar infarction restricted to the bilateral inferior vermis. During a
      course of recovery, he fell down in any directions while standing unattended. He
      was unable to keep the center of gravity on the feet base in an upright posture.
      The inferior vermis may participate in maintaining the center of gravity while
      standing.

PMID- 16642936
TI  - [A case of isolated hypoglossal nerve palsy probably due to dural arteriovenous
      fistula].
AB  - We report here a case of isolated hypoglossal nerve palsy probably caused by
      dural arteriovenous fistula (DAVF). A 51-year-old woman was admitted to our
      hospital complaining headache, tinnitus, and tongue atrophy. Three years before,
      she first experienced right-sided pulsatile headache and tinnitus which persisted
      until admission. One week before, she noticed her tongue deviated to right. On
      admission, physical and neurological examinations showed no abnormal findings
      except for bruits on right neck and bilateral orbital areas, and atrophy of right
      tongue. Brain MRI was not remarkable. MRA and conventional angiography disclosed
      DAVF. We conclude that differential diagnoses for isolated hypoglossal paralysis
      should include DAVF.

PMID- 16642937
TI  - [Severe orthostatic headache: a retrospective study on clinical presentation,
      radiological characteristics, and outcome in 12 patients].
AB  - To determine clinical characteristics and therapeutic outcome of severe
      orthostatic headache, we retrospectively studied 12 consecutive patients with
      severe orthostatic headache and unremarkable medical history. Headache is defined
      as severe when it interferes with patient's daily activities. Baseline
      characteristics of our patients are essentially similar to those reported in
      other published series of spontaneous intracranial hypotension: female
      preponderance; mean age of approximately 40 years; frequently associated nausea,
      hearing disturbances, or vertigo. Diffuse pachymeningeal gadolinium enhancement
      was demonstrated on MRI in 64% of the patients. Low CSF pressure was present in
      78%. Of 8 patients underwent radionuclide cisternography, CSF leak site was
      identified in 4 patients. Severe orthostatic headache resolved in 13.6 days in 5
      patients who received supportive measures only. Conservative treatment was
      ineffective in 7 patients. Of 6 patients treated with epidural blood patch (EBP),
      5 patients (83%) responded well to the first EBP. Patients with severe
      orthostatic headache which persisted 2 weeks and longer in spite of conservative
      measures are candidate for EBP. Our study and a literature review suggest that at
      least 2 EBPs should be performed for each leak site. Studies with more patients
      are needed for establishing a better treatment protocol for this syndrome.

PMID- 16642938
TI  - [Successful delivery following subcutaneous heparin administration in a 7-weeks
      pregnant patient suffering from cerebral venous thrombosis due to secondary
      protein S deficiency].
AB  - A 25-year-old, 7-weeks pregnant woman was admitted to the Nagaoka Red Cross
      Hospital in a state of confusion, following fever, headache and vomiting. Brain
      CT and MRI showed swelling in the bilateral thalami, basal ganglia and splenium
      of corpus callosum, and thrombosis of the internal cerebral veins and straight
      sinus. Initial treatment by intravenous heparin and glycerol was successful, and
      she regained her consciousness, leaving antegrade amnesia and childish character
      change. Her free protein S antigen was 32% (normal 60-127) and subsequently rose
      to 70% after delivery. She was diagnosed as having secondary protein S deficiency
      associated with pregnancy. Because warfarin can be teratogenic, subcutaneous
      heparin injection was prescribed in order to prevent thrombosis and the patient
      subsequently had a successful delivery. This was the first case in Japanese of
      successful delivery after subcutaneous heparin treatment in a patient with
      cerebral venous thrombosis.

PMID- 16642939
TI  - [Intermittent intravenous immunoglobulin infusion prevented relapses in patients
      with remission-exacerbation type chronic inflammatory demyelinating
      polyradiculoneuropathy].
AB  - The intravenous immunoglobulin infusion therapy (IVIg) has recently acquired an
      important role in the treatment of chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP). Some patients, however, require repetitive
      infusions to maintain the improvement. We planned a one-day therapy with 0.4 g/kg
      of IVIg in every 7 or 10 days for two CIDP patients who had required a 5-day
      course of IVIg in every month because of frequent exacerbations. Serum levels of
      IgG in both patients were kept as high as 2,000 mg/dl resulting in maintaining
      the improvement without any side effects.

PMID- 16642940
TI  - [The near response triad and asthenopia].

PMID- 16642941
TI  - [The influence on the static visual field of peripapillary chorioretinal atrophy-
      relation to axial length].
AB  - PURPOSE: To investigate the influence of axial length on white-on-white (W-on-W)
      perimetry and blue-on-yellow (B-on-Y) perimetry in myopic subjects according to
      the presence or absence of peripapillary chorioretinal atrophy (PPA). MATERIALS
      AND METHODS: Both B-on-Y and W-on-W perimetry were performed on 64 normal
      volunteers whose fundus photography was clear, and the presence or absence of PPA
      was distinct. We divided the 64 normal volunteers into a PPA group and a no-PPA
      group, and investigated the influence of axial length on both types of perimetry.
      RESULTS: As axial length extended in all cases and in the PPA group, mean
      deviation (MD) decreased significantly in both B-on-Y and W-on-W perimetry. There
      was no significant difference in the no-PPA group. In the PPA group, the retinal
      sensitivity decreased significantly at 22 test points in B-on-Y, as axial length
      extended; and this decrease occurred at 12 test points in W-on-W perimetry. These
      points were located mainly around the Mariotte blind spot, central points, and
      the area of Bjerrum. In the no-PPA group, the retinal sensitivity decreased
      significantly at only two test points in B-on-Y perimetry, but no decrease
      occurred at these test points in W-on-W perimetry. CONCLUSIONS: We should
      consider the presence of PPA and the influence of axial length in the
      interpretation of the results of W-on-W and B-on-Y perimetry.

PMID- 16642942
TI  - [Near triad measurement--accommodative pupillometry with horizontal eye tracking
      and its qualitative analysis].
AB  - PURPOSE: Recording of "near triad responses" was done by static accommodative
      stimulation to reveal the qualitative analysis of asthenopia. METHOD: Twelve
      healthy subjects in agegroups of 20, 30, and 40 years were examined before and
      after several hours of visual display terminal (VDT) work after informed consent.
      Three trials of forward <-> backward movement of focusing on a target were
      carried out. Response curves of horizontal eye tracking and pupillary diameter,
      that is, convergence with miosis and divergence with mydriasis, were recorded
      continuously, bilaterally and simultaneously by TriIRIS. RESULTS: 1) Normal
      patterns of vergence and pupillary responses with constant amplitudes were
      recorded in five subjects and were stable. 2 ) Gradual decline of the mydriatic
      peak was observed in two subjects, suggesting spastic accommodation. Increasing
      mydriatic peak or notching of mydriatic phase was seen in one eye each,
      suggesting tonic disaccommodation. These abnormal patterns were reversed by
      adequate refractive correction, and classified as an eye-fatigue group. 3)
      Abruption of miotic phase was observed in two cases of exophoria. 4) Low and
      declining amplitudes despite normal light response were observed in two subjects,
      suggesting debilitated accommodation, and they were classified as an eye-strain
      group. 5) Post-traumatic mydriatic anisocoria responded in parallel, suggesting
      paretic accommodation. CONCLUSIONS: Coordinated dynamics of near triad responses
      revealed remarkable characteristics of accommodative iris movements with
      vergence. These objective findings revealed the different patterns of functional
      disorder of accommodation.

PMID- 16642943
TI  - [Changes in diabetic retinopathy and visual acuity in patients with end-stage
      diabetic nephropathy after the introduction of hemodialysis].
AB  - PURPOSE: To study the diabetic retinopathy (DR) and visual acuity in patients
      with end-stage diabetic nephropathy in the predialysis period and the changes
      after the initiation of hemodialysis at Tokyo Postal Service Agency Hospital
      (TPSAH). METHODS: We retrospectively analyzed the systemic conditions and the
      stage of DR and visual acuity in the medical records, of 24 patients 48 eyes
      (male: female=20 : 4) with diabetic nephropathy, who were started on hemodialysis
      between June 1994 and August 2003 at TPSAH, and were followed ophthalmologically
      more than 6 months after the start of hemodialysis. RESULTS: At the start of
      hemodialysis, 46 of 48 eyes (95.8%) had already been treated by retinal
      photocoagulation. The DR activity was assessed as "low" in 62.5% of the patients
      at the start of hemodialysis, but 6 months later, over 95% of the patients were
      assessed as having "low-activity". At the start of hemodialysis visual acuity was
      less than 0.1 in 21% of the eyes, and over 0.7 in 42% of the eyes, and the ratio
      was stable in the follow-up period. In 2 eyes the stage of diabetic retinopathy
      became worse by more than one grade in Fukuda's grading of diabetic retinopathy,
      and in 4 eyes more than a 2 grade alteration in visual acuity was observed.
      CONCLUSIONS: After the start of hemodialysis, DR became less active relatively
      early, and only a few eyes became worse in visual acuity and DR.

PMID- 16642944
TI  - [Clinical evaluation of a measurement method for secretory IgA in tears].
AB  - PURPOSE: To evaluate the efficacy of measurement of secretory IgA (sIgA) in tears
      with tear sampling methods using filter paper, and to review sIgA measurement
      method for clinical application. SUBJECTS AND METHODS: Subjects were divided into
      the following 4 groups: a healthy control group, 29 eyes of 29 subjects; a
      contact lens group, 15 eyes of 15 subjects; a dry eye group, 13 eyes of 13
      subjects; and a herpes group, 6 eyes of 6 subjects. In all subjects the sIgA
      value in tears was measured. In addition, in eighteen eyes of 18 healthy control
      individuals, the tear sIgA value was measured three times, morning, noon, and
      night in one day, and the variation of tear sIgA value was checked. The tears
      were sampled by the Schirmer 1 method. Schirmer papers were eluted in 200 microl
      of 0.5 M NaCl and 0.5% Tween 20 in 0.05 M phosphate-buffered solution (pH 7.2).
      Tear sIgA value was measured by ELISA (enzyme-linked immunosorbent assay).
      RESULTS: Tear sIgA value was 1249.0+/-1025.0 microg/ ml in the healthy control
      group; 1057.4+/-1583.3 microg /ml in the contact len groups; 197.8+/-91.3
      microg/ml in the dry eye group; and 759.7+/-467.8 microg/ml in the herpes group.
      There was no significant difference between the healthy control group and the
      contact lens group, or the control group and the herpes group. There was a
      significantly (p<0.0001) low value in the dry eye group in comparison with the
      healthy control group. In the 18 healthy control individuals, there was a
      tendency for the tear sIgA value collected at noon to be higher. CONCLUSION:
      Measurment of the changes in tear sIgA values caused by inflammation of the
      lacrimal gland is useful as a clinical test of lacrimal gland function.

PMID- 16642945
TI  - [Clinical application of multifocal visual evoked potentials in children with
      epilepsy caused by intracranial disease].
AB  - PURPOSE: We investigated whether visual field defects could be objectively
      evaluated using multifocal visual evoked potential(m-VEP) in two children with
      epilepsy caused by intracranial disease in whom it was difficult to measure the
      visual field. METHODS: To determine normal waves in m-VEP, recording was
      performed using a visual evoked response imaging system(VERIS)Junior Science
      program (Mayo, Aichi, Japan) in 20 healthy children (20 eyes); peak latency and
      amplitude were used for assessment. In the two children with epilepsy, m-VEPs
      were recorded, and compared with the results of static perimetry or the lesions
      observed by Magnetic Resonance Imaging (MRI). RESULTS: In the 20 healthy
      children, there was no significant difference in the peak latency or amplitude
      among 4 quadrants by one-way analysis of variance. m-VEP in the children with
      epilepsy showed abnormal waves, corresponding to the visual field defects in the
      static perimetry or the lesions observed by MRI. CONCLUSIONS: Objective
      evaluation of visual field defects using m-VEP may be useful in children with
      epilepsy caused by intracranial disease in whom kinetic/static perimetry as a
      subjective examination is difficult.

PMID- 16642946
TI  - [Pulsation in polypoidal choroidal vasculopathy].
AB  - PURPOSE: To evaluate the relationship between pulsation and the fundus lesion in
      polypoidal choroidal vasculopathy (PCV). OBJECTIVE AND METHODS: We studied 26
      eyes with PCV by indocyanine green angiography (IA) with a heidelberg retina
      angiograph(HRA). The 26 eyes were classified into two groups; pulsatile PCV and
      non-pulsatile PCV. We evaluated the strength and the amplitude of the pulsation,
      and the frequency of subretinal hemorrhage within one year after the first IA.
      Seven eyes in the pulsatile PCV group were tested by HRA twice or more to
      evaluate the relationship between the fundus lesion and the change in the
      strength and the amplitude of pulsation. RESULTS: Subretinal hemorrhage occurred
      in 9 of 14 eyes with pulsatile PCV and in 2 of 12 eyes with non-pulsatile PCV
      (odds ratio : 12.5). The possibility of subretinal hemorrhage was significantly
      higher in pulsatile PCV than in non-pulsatile PCV. In 3 of the 7 eyes tested
      twice or more, the fundus lesion worsened as the pulsation strengthened and the
      area of pulsation enlarged. In 1 of the 7 eyes, the fundus lesion improved as the
      pulsation weakened and the area of pulsation decreased. CONCLUSION: There is a
      good possibility that strengthened and extended pulsation is related to
      increasing subretinal hemorrhage in PCV patients.

PMID- 16642947
TI  - [Visual prognosis of branch retinal vein occlusion with macular edema].
AB  - PURPOSE: To evaluate visual outcome and prognostic factors of branch retinal vein
      occlusion (BRVO) combined with macular edema, when no aggressive treatment is
      performed. PATIENTS AND METHODS: We retrospectively analyzed 80 eyes of 80
      patients of BRVO associated with macular edema. The average age was 65.7 years
      and the average follow-up period was 32.1 months. Oral or instillation drug
      therapy was conducted in 42 eyes and peripheral scatter argon laser
      photocoagulation for the capillary non-perfusion area was carried out in 61 eyes
      (photocoagulation for macula was excluded). RESULTS: Baseline visual acuity(BVA)
      and final visual acuity(FVA) had a positive correlation (r= 0.60, p< 0.001). 69%
      of eyes with BVA of 0.1 or less remained at FVA 0.1 or worse, while 78% of eyes
      with BVA of 0.8 or better maintained FVA of 0.8 or better. Visual acuity improved
      in 26%, remained unchanged in 54%, and deteriorated in 20% during follow-up
      periods. In the eyes with visual loss the deterioration occurred in the early
      periode from onset, but in the eyes with visual improvement the visual acuity
      tended to improve steadily. CONCLUSIONS: Even if macular edema occurs, some of
      the BRVO eyes can attain good visual acuity. However, we recommend aggressive
      treatment when the best-corrected acuity is poor or when the visual acuity
      worsens gradually, because there is a strong possibility that the visual
      prognosis will be poor.

PMID- 16642948
TI  - [The long-term outcome of trabeculectomy in advanced glaucoma].
AB  - PURPOSE: We evaluated retrospectively the surgical outcome of trabeculectomy in
      patients with advanced glaucoma. METHODS: We studied 18 eyes of 18 patients with
      advanced glaucoma (mean age: 71.2 years, mean follow-up period: 41.1 months). In
      each eye, the visual field was at stage 5 of Aulhorn-Greve's classification
      before surgery. RESULTS: Two eyes showed extreme hypotony (< 2 mmHg) 3 days after
      surgery and lost the central visual field permanently. Another 2 of 4 eyes which
      could not be maintained below 15 mmHg showed a worsening of visual field
      disturbance within stage 5 of Aulhorn-Greve's classification. The final visual
      acuity was 0.7 or better in 9 eyes (50.0%), 0.1 or worse in 2 eyes (11.1%). The
      final intraocular pressure (IOP) was below 10 mmHg without and with medication in
      8 eyes (44.4%) and 2 eyes (11.1%) respectively. The final IOP was below 15 mmHg
      without and with medication in 11 eyes (61.1%) and 3 eyes (16.7%) respectively.
      Postoperative complications were observed in 4 eyes (22.2%). CONCLUSIONS: The
      cause of postoperative central visual field worsening was associated with extreme
      intraocular hypotony (2 mmHg) rather than IOP elevation due to bleb dysfunction.
      This surgery may be effective as 14 eyes (78%) were able to maintain visual
      acuity and the central visual field.

PMID- 16642949
TI  - [A case of monoclonal gammopathy with corneal stroma deposits].
AB  - BACKGROUND: Monoclonal gammopathy is a group of disorders characterized by
      proliferation of a single clone of plasma cells that produce monoclonal protein.
      Sometimes benign monoclonal gammopathy that is a symptomatic can turn into a
      malignancy like multiple myeloma. We present a case of monoclonal gammopathy with
      corneal deposits which was treated with deep lamellar keratoplasty (DLKP). The
      corneal button obtained at the time of DLKP was studied with both light and
      electron microscopy. CASE: Fine corneal deposits developed bilaterally in a 69
      year-old man. There was no family history of ocular diease. RESULTS: We diagnosed
      monoclonal gammopathy in a blood test that showed elevation of serum
      immunoglobulin G and the Kappa chain. The corneal button obtained during DLKP was
      analyzed histologically and ultrastructurally. Electron microscopy showed
      electron-dense deposits composed of fine parallel filaments in the corneal
      epithelium and stroma. CONCLUSIONS: Corneal deposits of unknown origin might turn
      into monoclonal gammopathy that could be a life-threatening disease. It is
      important for ophthalmologists to check the whole body of a patient when finding
      corneal deposits.

PMID- 16642950
TI  - [A case of severe glaucoma with pseudopemphigoid successfully treated by
      filtration surgery using amniotic membrane].
AB  - BACKGROUND: It is necessary to decrease topical anti-glaucoma medication for
      severe glaucoma with pseudopemphigoid caused by anti-glaucoma eye drops. Glaucoma
      filtrating surgery is often needed instead of medication, but the prognosis is
      poor because it induces scar fomation and makes the filtrating bleb vanish. CASE:
      An 85-year-old male patient with exfoliation syndrome had twice undergone
      glaucoma surgery about ten years previously. His intra-ocular pressure (IOP) was
      high despite topical anti-glaucoma medication. At the first examination in our
      hospital, he had severe superficial punctate keratopathy, blephariticshortening
      and symblepharon, and we therefore diagnosed severe pseudopemphigoid induced by
      anti-glaucoma eye drops. Because his IOP could not be controlled by topical and
      general medication, we conducted a glaucoma filtrating operation using amniotic
      membrane. CONCLUSION: The administration of oral anti-inflammatory drugs before
      and after surgery and the use of amniotic membrane prevented post-operative scar
      formation and the progress of symblepharon, resulting in the successful control
      of IOP after surgery.

PMID- 16642951
TI  - [Notes on ophthalmologic terminology. 2. Orthoptists and ORT (orthoptics)].

PMID- 16642952
TI  - [Program for continuing professional education in ophthalmology. A review 26 :
      Electroretinogram].

PMID- 16642953
TI  - [Development of advanced pediatric medicine in Asia].

PMID- 16642954
TI  - [Development of a molecular target therapy on the basis of global gene analyses
      of gastrointestinal carcinoma].

PMID- 16642955
TI  - Fatal case of amiodarone-induced acute respiratory distress syndrome in a patient
      with severe left ventricular dysfunction due to extensive anterior acute
      myocardial infarction.
AB  - We here report a case of 71-year-old man with acute extensive anterior myocardial
      infarction, who was complicated with ventricular tachycardia (VT) even after
      successful percutaneous coronary intervention. As intravenous administration of
      nifekalant terminated VT, we started oral administration of amiodarone (day 1).
      We gave 400 mg of amiodarone a day for the first week and 200 mg a day from the
      second week. The patient was stable with normoxia by day 20, in spite of
      pulmonary congestion-like infiltrates on chest X-ray. On day 21, he was
      complicated with acute respiratory distress syndrome. Immediate discontinuance of
      amiodarone and high-dose pulse glucocorticoid therapy with intubation slightly
      improved the infiltrations on chest X-ray. However, glucocorticoid therapy
      induced hyperglycemia with an increase in plasma osmolality, complicated with
      hypoalbuminemia, and gastrointestinal bleeding. Despite treatment with a large
      amount of saline, high-doses of catecholamines, and blood transfusion, the
      patient died on day 28. It is sometimes difficult to diagnose congestive heart
      failure or amiodarone-induced pulmonary infiltrates in patients with severe left
      ventricular dysfunction.

PMID- 16642956
TI  - Central nervous system regulation of food intake.

PMID- 16642957
TI  - Metabolic actions of adipocyte hormones: focus on adiponectin.
AB  - The obesity epidemic has focused attention on the endocrine function of adipose
      tissue. Adipose tissue secretes leptin, cytokines, complement factors, and
      components of the coagulation cascade, most of which are increased in obesity. In
      contrast, a strong negative correlation exists between adiponectin and adiposity,
      insulin sensitivity, diabetes, vascular inflammation, and atherosclerosis.
      Adiponectin treatment in rodents increases insulin sensitivity and reduces lipids
      and atherogenesis. Chronic and central adiponectin treatment reduces weight,
      glucose, and lipids. The insulin-sensitizing action of thiazolidinediones is
      mediated, in part, through adiponectin. A causal role of adiponectin in diabetes,
      dyslipidemia, and atherosclerosis has been established in knockout mice.
      Therefore, adiponectin seems to be a marker of obesity-related diseases and a
      potential therapeutic target.

PMID- 16642958
TI  - Why visceral fat is bad: mechanisms of the metabolic syndrome.

PMID- 16642959
TI  - Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human
      model.
AB  - OBJECTIVE: To review the evidence for and against the role of visceral adipose
      tissue as a major contributor to the metabolic complications of obesity through
      abnormal regulation of lipolysis. RESEARCH METHODS AND PROCEDURES: Data from
      investigators in the field who have studied visceral adiposity and metabolic
      health and/or regional and systemic free fatty acid (FFA) release were
      considered. RESULTS: Although visceral fat mass was positively correlated with
      adverse health consequences and excess FFA availability, visceral fat was not the
      source of excess systemic FFA availability. Upper body non-visceral fat
      contributes the majority of FFAs in lean, obese, diabetic, and non-diabetic
      humans. Increasing amounts of visceral fat probably result in greater hepatic FFA
      delivery. DISCUSSION: Systemic, as opposed to hepatic, insulin resistance is
      unlikely to be caused by high rates of visceral adipose tissue lipolysis.

PMID- 16642960
TI  - Metabolic syndrome: adenosine monophosphate-activated protein kinase and malonyl
      coenzyme A.
AB  - The metabolic syndrome can be defined as a state of metabolic dysregulation
      characterized by insulin resistance, central obesity, and a predisposition to
      type 2 diabetes, dyslipidemia, premature atherosclerosis, and other diseases. An
      increasing body of evidence has linked the metabolic syndrome to abnormalities in
      lipid metabolism that ultimately lead to cellular dysfunction. We review here the
      hypothesis that, in many instances, the cause of these lipid abnormalities could
      be a dysregulation of the adenosine monophosphate-activated protein kinase
      (AMPK)/malonyl coenzyme A (CoA) fuel-sensing and signaling mechanism. Such
      dysregulation could be reflected by isolated increases in malonyl CoA or by
      concurrent changes in malonyl CoA and AMPK, both of which would alter
      intracellular fatty acid partitioning. The possibility is also raised that
      pharmacological agents and other factors that activate AMPK and/or decrease
      malonyl CoA could be therapeutic targets.

PMID- 16642961
TI  - New insights into the pathogenesis of insulin resistance in humans using magnetic
      resonance spectroscopy.
AB  - Insulin resistance plays a major role in the pathogenesis of type 2 diabetes, yet
      despite much effort, the underlying factors that are responsible for it are
      poorly understood. In this review, we focus on some recent advances in our
      understanding of the pathogenesis of insulin resistance in humans that have been
      made using magnetic resonance spectroscopy.

PMID- 16642962
TI  - Metabolic syndrome: focus on dyslipidemia.

PMID- 16642963
TI  - Assessment of the physiologic stress response by quantification of fecal
      corticosteroids.
AB  - Noninvasive techniques to monitor reproductive or stress hormones are now widely
      used in captive and free-ranging wildlife. These methods offer great advantages
      and deserve to be used also in laboratory rodents. However, we remain naive about
      factors that may influence the accuracy of these techniques. The aim of this
      study was to evaluate the adequacy of measuring the concentration of cortisol
      fecal metabolites to assess the physiologic stress response. Ten adult female
      Syrian hamsters were ovariectomized, and all feces voided were collected daily
      for 4 d before and 5 d after surgery. Cortisol fecal metabolites were extracted
      and quantified by radioimmunoassay. We determined per-gram fecal cortisol
      metabolite concentrations, total 24-h fecal output and total 24-h fecal cortisol
      metabolite production. Surgery considerably affected fecal output, and using per
      gram versus total cortisol metabolites led to different conclusions: whereas
      concentrations increased significantly just after ovariectomy and decreased on
      subsequent days, the total excreted cortisol metabolites varied in a symmetrical
      pattern. Therefore, the relative per-gram measure of hormones may not reflect the
      total amount of circulating hormones, because these measures are comparable only
      if the volume of the material in which the hormone is contained is the same in
      the 2 groups.

PMID- 16642964
TI  - Pharmacokinetics of buprenorphine after intravenous administration in the mouse.
AB  - Buprenorphine is a potent partial m-opioid agonist that is used as an analgesic
      in animals and humans to ameliorate moderate to severe pain and in the treatment
      of opiate addiction as an alternative to methadone maintenance. The purpose of
      this study was to characterize the pharmacokinetics of buprenorphine after
      intravenous administration in mice. Mice (n=48) were given 2.4 mg/kg
      buprenorphine (HCl salt) by intravenous bolus injection, and groups of 4 mice
      were euthanized at 5, 15, and 30 min and 1, 2, 3, 5, 7, 9, 12, 18, and 24 h after
      drug administration. Plasma concentrations of buprenorphine and norbuprenorphine
      were determined using liquid chromatography-tandem mass spectrometry. By using
      the mean concentrations at each time point (n=4), pharmacokinetic parameters were
      estimated for buprenorphine using a 3-compartment model with the reciprocal of
      the predicted concentration as the weight factor. The estimated values for the
      exponents of the 1st, 2nd, and terminal compartments; volume of distribution at
      steady state; clearance; and area under the concentration-time curve were 12.8/h,
      2.13/h, 0.239/h, 6.5 l/kg, 4.3 l/h/kg, and 559 microg/lxh, respectively. In
      addition, we compare the pharmacokinetic disposition of buprenorphine in the
      mouse with that previously reported for other species.

PMID- 16642965
TI  - Comparison of the stress response in rats to repeated isoflurane or CO2:O2
      anesthesia used for restraint during serial blood collection via the jugular
      vein.
AB  - The primary objective of this study was to compare the effect of 2 commonly used
      anesthetics, isoflurane and CO2, on the physiologic stress hormone,
      corticosterone, in rats during serial blood collections. Circulating
      corticosterone concentrations were monitored during serial jugular blood sampling
      in rats exposed to either isoflurane or CO2 anesthesia. Blood was drawn under
      anesthesia at 6 time points (initial sampling and 0.5, 1, 2, 3, and 24 h after
      initial sampling) across a 24-h period. The results indicated that corticosterone
      levels in both anesthesia groups showed a similar pattern of stimulation,
      indicated by a sharp increase in circulating concentrations by the 0.5-h time
      point, with further elevation at 1 h, and a decline at subsequent time points.
      Isoflurane-treated animals showed higher baseline levels of corticosterone at the
      initial sampling. However, the increase in corticosterone at subsequent time
      points was significantly higher for animals exposed to CO2, suggesting that the
      cumulative effects of repeated exposure to stressful stimuli was more evident for
      this type of anesthesia. The apparent reduction in stress effects of isoflurane
      as opposed to CO2, coupled with other published adverse effects of CO2, suggests
      that isoflurane is the better choice when anesthesia is needed for serial blood
      collection. However, availability of equipment for delivery of anesthetic,
      scavenging of waste gasses, familiarity of personnel with the anesthetic, and the
      potential effect of the anesthetic on research endpoints should all be considered
      in choosing between the 2 anesthetics.

PMID- 16642966
TI  - Efficacy and safety of topical selamectin to eradicate pinworm (Syphacia spp.)
      infections in rats (Rattus norvegicus) and mice (Mus musculus).
AB  - We evaluated the efficacy and safety of topical selamectin, a novel avermectin,
      in eliminating naturally acquired Syphacia muris infections in rats and S.
      obvelata infections in mice. S. muris-positive rats were assigned randomly to 4
      groups: selamectin (0.6 mg/kg), selamectin (6.0 mg/kg), fenbendazole-medicated
      (150 ppm) chow, and untreated. S. obvelata-positive mice were allocated into 4
      groups similar to those for rats. Animals not exposed to pinworm-contaminated
      bedding were designated as negative controls. Treatment success was assessed
      weekly by anal tape impressions and by necropsy examinations at the end of week
      9. Evaluations of intestinal contents at necropsy revealed that, although safe,
      topical selamectin was 100% ineffective in eliminating Syphacia spp. infections
      in rats and mice. Treatment with fenbendazole-medicated chow resulted in negative
      anal tape impressions beginning at week 2 in rats and week 1 in mice. Negative
      anal tape impressions in fenbendazole-treated animals were confirmed by negative
      intestinal content evaluations. Of the 2 treatments evaluated, fenbendazole
      medicated chow remains an effective and practical method to eliminate pinworm
      infections in mice and rats.

PMID- 16642967
TI  - Successful introduction of Macaca nemestrina infants to their mothers after
      cesarean delivery.
AB  - Four Macaca nemestrina infants delivered via cesarean section were introduced to
      their mothers after surgery. All 4 introductions were successful, although
      methods differed slightly between dam-infant pairs. Pairs were considered
      successful when the mother displayed affiliative behavior towards the infant
      (including grooming), cradled it ventrally, and nursed it sufficiently to
      maintain infant health. The dams were sedated lightly with ketamine prior to
      introduction to reduce the possibility of aggression to caregivers and infants.
      The dams were checked for lactation, and each infant was swabbed with its
      placenta and with its mother's vaginal secretions prior to placement in the dam's
      cage. During the initial exposure, all 4 mothers picked up their infants within
      1.5 h after introduction. Three of the 4 dam-infant pairs were fully successful
      during the initial exposure (24 h postdelivery), that is, the infants began to
      nurse within 2.5 h of affiliative contact. The 4th dam-infant pair required 3 d
      of successive exposures before the infant was nursed adequately. Infant health
      and maternal behavior determined the length of exposure. The optimal duration of
      these introductory encounters appeared to be between 2 and 3.5 h, to allow
      sufficient time for the dam's recovery from sedation while avoiding adverse
      effects on infant health. These observations demonstrate that cesarean-delivered
      M. nemestrina infants can be successfully united with their mothers, although it
      sometimes may require prolonged exposures on successive days.

PMID- 16642968
TI  - Response of lightly and highly pigmented porcine skin (Sus scrofa domestica) to
      single 3.8-microm laser radiation pulses.
AB  - The purpose of this study was to determine the effect of melanin on skin response
      to single 3.8-microm, 8-micros laser pulses and the difference in lesion
      formation thresholds. Our hypothesis was that pigmentation would play a
      significant role in skin energy absorption at 3.8 microm. Previous studies
      comparing pigmented and lightly pigmented porcine skin with human skin found that
      compared with Yorkshire pigs, Yucatan minipigs were a superior model for laser
      skin exposure because of their higher pigmentation levels. In the current study,
      10 pigs under general anesthesia were exposed to 3.8-microm laser pulses ranging
      from 0.01 J/cm2 to 93 J/cm2. Gross examinations and skin biopsies were done 24 h
      after laser exposure, and histologic examinations were conducted on these tissue
      samples. The 24-h effective dose (ED50) was determined to be 4.5 J/cm2 for
      Yucatan mini-pigs and 2.6 J/cm2 for Yorkshire pigs. As deposited energy was
      increased, the lesion presentation progressed from desiccation of the superficial
      layer of epidermis (4 J/cm2) to desiccation with inflammatory centers (14 J/cm2),
      and finally to replacement of inflammatory areas with an epidermal ulcerated
      central area (=21 J/cm2). Therefore we found no statistical difference between
      the 24-h ED50 of the 2 breeds of pigs, nor was there any difference in histologic
      presentation at 24 h postexposure.

PMID- 16642969
TI  - Human cancer xenograft perfusion in situ in rats: a new perfusion system that
      minimizes delivery time and maintains normal tissue physiology and responsiveness
      to growth-inhibitory agents.
AB  - We developed an artificial lung and catheter system for perfusing tissue-isolated
      tumors in situ that dramatically minimizes perfusate delivery time. Our
      investigations demonstrated that the circadian neurohormone melatonin (MLT),
      eicosapentaenoic acid (EPA), and conjugated linoleic acid (CLA) inhibit growth
      and metabolism in several rodent and human tumors. These anticancer agents
      function in a receptor-mediated manner to suppress tumor uptake of linoleic acid
      (LA), the principal tumor growth-promoting fatty acid, and its conversion to the
      mitogenic agent 13-hydroxyoctadecadienoic acid (13-HODE). Using this perfusion
      system and MCF-7 human breast xenografts, we examined the efficacy and timing of
      perfusate delivery to tumors. Tumors were perfused with rat donor blood to
      establish baseline LA uptake values; after 36 min of perfusion, we supplemented
      the perfusate with MLT, EPA, or CLA and collected arteriovenous whole-blood
      samples over 5-min intervals for a total perfusion period of 70 min. Arterial
      blood pH, pO2, and pCO2 (mean+/-33.7+/-1.9, and 59.8+/-1.9 mm Hg, respectively;
      none of these values varied during the perfusions. Tumor LA uptake and 13-HODE
      production were 1.06+/-0.28 microg/min/g and 1.38+/-0.02 ng/min/g, respectively,
      and were completely suppressed within 5 min after delivery of anticancer agents
      to the tissue. This new system provides rapid perfusate delivery for use with
      both normal and neoplastic tissues while maintaining normal physiologic tissue
      parameters.

PMID- 16642970
TI  - Evaluation of a potential stress effect in rat adjuvant arthritis by using a new
      and efficient plethysmograph.
AB  - We describe the basis of a new design for a user-friendly and easily reproduced
      mercury-displacement plethysmograph. This system was validated using the rat
      adjuvant-induced arthritis model in female Lewis rats. Furthermore, 2 different
      caging systems were evaluated to ensure that caging did not have an effect on
      disease progression and severity. These groups were evaluated further under
      frequent- and infrequent-handling conditions. Housing had less effect on the
      amount of swelling seen during the disease than did the amount of handling.
      Frequent handling significantly reduced the degree of paw swelling. Frequently
      handled, arthritic rats housed 5 rats per cage in the Box B system also lost a
      biologically significant amount of weight by the end of the study. Therefore, we
      do not recommend housing more than 4 rats per cage under these conditions.

PMID- 16642971
TI  - Controlling allergens in animal rooms by using curtains.
AB  - The reduction and control of allergens in the animal facility is important for
      staff working with laboratory animals. This study was designed to evaluate the
      efficiency of perforated Makrolon curtains in front of racks as a method to
      reduce the amount of allergen in the animal room. The experimental situation we
      studied provides some information regarding allergen disposition in animal rooms
      but is clearly artificial and does not reflect a typical, 'real-world'
      environment in terms of preventing exposure of workers to allergens. Plastic
      curtains with holes were placed in front of racks, and a corridor between the
      racks and a curtain was present. The room was ventilated with air, which was
      blown into the room through the middle of the corridor, flowing downstream and
      passing through the holes in the curtain. This set-up resulted in air flow from
      the corridor through the curtain. Air samples were collected from sites in the
      corridor and behind the curtain. The samples were analyzed for the allergen Mus
      m1, and the amount of allergen was calculated. The results show air flow from the
      aisle through the holes in the curtains and through the racks behind the
      curtains, and this flow keeps allergen behind the curtains and prevents its
      spread from the cages into the aisle. The present study shows that the use of
      curtains in front of the cage racks is an efficient way to prevent spread of
      allergens from rodent cages to the entire animal room.

PMID- 16642972
TI  - Calcinosis circumscripta in a common marmoset (Callithrix jacchus jacchus).
AB  - A 2.5-y-old, male common marmoset (Callithrix jacchus jacchus) developed a 2-cm,
      interscapular, subcutaneous mass with variably firm and cystic areas. Radiographs
      demonstrated a radiodense mass in close proximity to a previously implanted
      microchip. Fine-needle aspiration yielded a chalky liquid that, on cytologic
      examination, contained amorphous debris. Aerobic and anaerobic cultures were
      negative. Surgical excision required extensive dissection, with the mass
      infiltrating deep to the scapula and extending to the mammary gland. The mass
      weighed 30 g and comprised 10% of the animal's body weight. Microscopic
      examination demonstrated multifocal, variably sized, amorphous aggregates of
      granular, basophilic material (mineral) in the subcutis and extending to skeletal
      muscle. Mineral deposits were surrounded by macrophages, giant cells, and fibrous
      connective tissue. A focal area of ectopic bone production was present.
      Crystallographic analysis and x-ray diffractometry determined the material to be
      comprised of 100% hydroxyapatite. These findings were consistent with a diagnosis
      of calcinosis circumscripta. Systemic metabolic abnormalities were excluded based
      on examination of complete blood count, serum chemistry, and ionized calcium.
      Calcinosis circumscripta in the common marmoset has not previously been reported,
      although the lesion has been reported to occur in rhesus macaques and is well
      described in man and dogs. Accumulation of calcium deposits and production of
      ectopic bone in a marmoset is interesting in light of this species's unique
      calcium and vitamin D metabolism.

PMID- 16642973
TI  - Primary amenorrhea associated with ovarian leiomyoma in a baboon (Papio
      hamadryas).
AB  - A 6-y-old female baboon was examined due to absence of menstrual cycling and
      secondary sex characteristics and failure to reproduce. The mammary glands and
      vaginal introitus were hypoplastic, the clitoris was prominent, and the perineal
      skin was immature with lack of cyclic color alterations and sexual swelling.
      Evaluation of the reproductive tract revealed a hypoplastic uterus and
      rudimentary ovaries with the presence of an ovarian leiomyoma within the right
      ovary. Hormonal values (estradiol, progesterone) were low and comparable to those
      of adult males or ovariectomized females. Adrenal and pituitary hormones
      (dehydroepiandrosterone, luteinizing and follicular stimulating hormones) and
      pituitary structure were within normal limits for this species. The baboon had a
      normal 42,XX karyotype. These findings suggest primary amenorrhea due to ovarian
      dysgenesis. This is the first report of a case of primary amenorrhea due to
      ovarian dysgenesis with a normal karyotype associated with a unilateral ovarian
      leiomyoma in the baboon. Continued studies of noncycling female nonhuman primates
      in captive breeding colonies may lead to a greater understanding of the
      underlying causes of this condition.

PMID- 16642974
TI  - Persistent left superior vena cava in sheep.
AB  - Persistent left superior vena cava (PLSVC) is a rare finding. To the best of our
      knowledge, this is the first report of PLSVC in sheep. In this case, PLSVC was
      confirmed using angiography.

PMID- 16642975
TI  - Structural identification of highly polar nontarget contaminants in drinking
      water by ESI-FAIMS-Q-TOF-MS.
AB  - Drinking water is a complex mixture that contains thousands of naturally
      occurring and anthropogenic contaminants. Liquid chromatography-mass spectrometry
      (LC-MS) methods have gained a tremendous popularity in monitoring nonvolatile,
      highly polar, and thermally labile components in drinking water. It is well
      recognized, however, that there are difficulties or limitations of LC-MS methods
      associated with (1) significant resources (time and effort) involved in sample
      preparation (preconcentration, fractionation, separation), (2) low screening
      capacity for target contaminants, and (3) insufficient capabilities for
      structural identification (elucidation) of nontarget contaminants. Consequently,
      LC-MS methods are mainly used for the detection of target contaminants (compounds
      identified in drinking water before), seldom for the structural identification of
      abundant nontarget pollutants (unidentified pollutants in drinking water), and
      almost never for the structural identification of nontarget components at a trace
      level. The paper presents a new method of electrospray ionization high field
      asymmetric waveform ion mobility spectrometry mass spectrometry (ESI-FAIMS-MS),
      which can detect a large number of water pollutants in a quick and convenient
      fashion without preconcentration, fractionation, derivatization, or column
      separation. Most importantly, the method provides structural identification of
      nontarget contaminants including species present in drinking water at a sub-parts
      per-billion concentration level. The identification of previously unknown
      contaminants was based on mass measurements of investigated ions and their
      fragments in mass and tandem mass spectrometry. Elemental compositions of these
      ions, determined by mass measurements, were used to link dissociation patterns of
      investigated species with their chemical structures. Characterization of
      nontarget contaminants of chlorine-treated drinking water by ESI-FAIMS-MS has
      revealed many previously unknown disinfection byproducts. The most intriguing
      compound, from a group of highly polar hydroxycarboxylic acids discovered in the
      study, was the most abundant component of drinking water, glycolic acid. Glycolic
      acid (toxic to kidneys and associated with a moderate maternal toxicity) has
      never been considered as a drinking water contaminant, despite the fact that it
      is present in drinking water at a higher concentration (high ppm) than
      concentrations of highly polar water pollutants that had attracted most attention
      in the past. The process of structural elucidation of discovered pollutants,
      including ultratrace contaminants representing a variety of carboxylic acids,
      will be presented in detail. The structural identification of highly polar
      contaminants in drinking water presented in the paper is rarely reported in the
      literature. The key experimental feature of the ESI-FAIMS-MS method is FAIMS
      separation, which significantly improves the identification capabilities of mass
      spectrometry.

PMID- 16642976
TI  - Aptamer-conjugated nanoparticles for selective collection and detection of cancer
      cells.
AB  - We have developed a method for the rapid collection and detection of leukemia
      cells using a novel two-nanoparticle assay with aptamers as the molecular
      recognition element. An aptamer sequence was selected using a cell-based SELEX
      strategy in our laboratory for CCRF-CEM acute leukemia cells that, when applied
      in this method, allows for specific recognition of the cells from complex
      mixtures including whole blood samples. Aptamer-modified magnetic nanoparticles
      were used for target cell extraction, while aptamer-modified fluorescent
      nanoparticles were simultaneously added for sensitive cell detection. Combining
      two types of nanoparticles allows for rapid, selective, and sensitive detection
      not possible by using either particle alone. Fluorescent nanoparticles amplify
      the signal intensity corresponding to a single aptamer binding event, resulting
      in improved sensitivity over methods using individual dye-labeled probes. In
      addition, aptamer-modified magnetic nanoparticles allow for rapid extraction of
      target cells not possible with other separation methods. Fluorescent imaging and
      flow cytometry were used for cellular detection to demonstrate the potential
      application of this method for medical diagnostics.

PMID- 16642977
TI  - Total platinum concentration and platinum oxidation states in body fluids,
      tissue, and explants from women exposed to silicone and saline breast implants by
      IC-ICPMS.
AB  - Ion chromatography-inductively coupled plasma-mass spectrometry was used to
      determine the total platinum concentration and platinum oxidation states in
      samples from women exposed to silicone and saline breast implants. Samples
      included the following: whole blood, urine, hair, nails, sweat, brain tissue,
      breast milk, and explants. Mean Pt concentration in samples from women exposed to
      silicone breast implants were as follows: whole blood, 568.1 +/- 74.77 pmol/L (n
      = 9); urine, 1.77 +/- 0.847 mug/g of creatinine (n = 10); hair, 2.13 +/- 2.984
      ng/g (n = 9); nails, 0.88 +/- 0.335 ng/g (n = 9); sweat, 1.90 +/- 1.691 ng/g (n =
      9); breast milk, 1.09 +/- 0.316 mug/L (n = 6). Pt in explanted silicone breast
      implant gel (n = 9) occurred mainly in the +2, +4, and +6 oxidation states. Pt in
      whole blood (n = 7) and breast milk samples (n = 6) from women exposed to
      silicone breast implants occurred mainly in the +2 and +4 oxidation states.
      Saline breast implant fluid (n = 2) did not contain detectable levels of Pt. This
      is the most comprehensive report, to date, to show that women exposed to silicone
      breast implants have Pt levels that exceed that of the general population, and
      the first report, to date, to document the various Pt oxidation states present in
      samples from women exposed to silicone breast implants.

PMID- 16642978
TI  - Characterization of prolidase activity using capillary electrophoresis with
      tris(2,2'-bipyridyl)ruthenium(II) electrochemiluminescence detection and
      application to evaluate collagen degradation in diabetes mellitus.
AB  - A new method for prolidase (PLD, EC 3.4.13.9) activity assay was developed based
      on the determination of proline produced from enzymatic reaction through
      capillary electrophoresis (CE) with tris(2,2'-bipyridyl)ruthenium(II)
      [Ru(bpy)3(2+)] electrochemiluminescence detection (ECL). A detection limit of
      12.2 fmol (S/N = 3) for proline, corresponding to 1.22 x 10(-8) units of
      prolidase catalyzing for 1 min was achieved. PLD activity determined by CE-ECL
      method was in agreement with that obtained from the classical Chinard's one. CE
      ECL showed its powerful resolving ability and selectivity as no sample
      pretreatment was needed and no interference existed. The clinical utility of this
      method was successfully demonstrated by its application to assay PLD activity in
      the serum of diabetic patients in order to evaluate collagen degradation in
      diabetes mellitus (DM). The results indicated that enhanced collagen degradation
      occurred in DM.

PMID- 16642979
TI  - Optimization of dielectrophoretic DNA stretching in microfabricated devices.
AB  - We have found that the surface and bulk solution properties in a microfabricated
      device affect the degree and probability of electrostretching of DNA molecules.
      Using lambda phage DNA, we found that significantly hydrophilic surfaces between
      the electrodes decrease the efficiency of stretching. Surfaces treated with
      higher silane (trimethylchlorosilane) concentrations performed better presumably
      due to the decreased nonspecific adsorption of DNA on these surfaces compared to
      their more hydrophilic counterparts. The shape and dimensions of the electrodes
      also affected the efficiency of stretching. Both liftoff and metal etching
      methods produced electrodes with random microscopic peaks along the electrode's
      edge and were poorly suited for stretching. Annealing the electrodes (450 degrees
      C for 10 min) removed most of these peaks and allowed for more controlled
      stretching to be obtained. We also found that thin electrodes (65 nm) gave close
      to a 90% success rate of DNA stretching but stretching with thick electrodes (350
      nm) produced only a 20% success rate.

PMID- 16642980
TI  - Application of power spectra patterns in Fourier transform square wave
      voltammetry to evaluate electrode kinetics of surface-confined proteins.
AB  - This paper describes an application of Fourier transform (FT) voltammetry that
      provides a quantitative evaluation of the electron-transfer kinetics of protein
      molecules attached to electrode surfaces. The potential waveform applied in these
      experiments consists of a large-amplitude square wave of frequency f superimposed
      onto the traditional triangular voltage used in dc cyclic voltammetry. The
      resultant current-time response, when Fourier transformed into the frequency
      domain, provides patterns of data at the even harmonic frequencies that arise
      from nonlinearity in the Faradaic response. These even harmonic contributions are
      ideally suited for kinetic evaluation of electron-transfer processes because they
      are highly selective to quasi-reversible behavior (insensitive to reversible or
      irreversible processes) and almost devoid of background charging current. Inverse
      FT methods can then be used to provide the wave shapes of the dc as well as the
      ac voltammetric components and other characteristics employed to detect the level
      of nonideality present relative to theoretical models based upon noninteracting
      surface-confined molecules. The new form of data evaluation has been applied to
      the electron-transfer properties of a typical biological electron carrier, the
      blue copper protein azurin, immobilized on polycrystalline gold electrodes
      modified with self-assembled monolayers of different length alkanethiols. Details
      of the electrode kinetics (rates of electron transfer, dispersion, and charge
      transfer coefficients) as a function of alkanethiol, apparent surface coverage,
      and capacitance are all deduced from the square wave (FT-inverse FT) protocol,
      and the implications of these findings are considered.

PMID- 16642981
TI  - Development of HPLC/ESI-MS and HPLC/1H NMR methods for the identification of
      photocatalytic degradation products of iodosulfuron.
AB  - In the present study, HPLC/ESI-MS and stopped-flow HPLC/1H NMR methods were
      developed and applied to separate and characterize the byproducts arising from
      TiO2-catalyzed photodegradation of the herbicide iodosulfuron methyl ester (IOME)
      in aqueous solution under UV irradiation. Prior to identification, irradiated
      solutions of IOME (200 and 1000 mg.L(-1)) were concentrated by solid-phase
      extraction using two cartridges: Isolute C18 and Isolute ENV+. Analytical
      separation was achieved on a C18 reversed-phase column with ACN/H2O (HPLC/MS) or
      ACN/D2O (HPLC/NMR) as mobile phase and a linear gradient with a chromatographic
      run time of 35 min. The combination of UV and MS data allowed the structural
      elucidation of more than 20 degradation products, whereas 1H NMR data permitted
      an unequivocal confirmation of the identities of major products and the
      differentiation of several positional isomers, in particular, the hydroxylation
      isomers. The obtained results permitted us to propose a possible degradation
      scheme and to put in evidence the presence of privileged sites for the attack of
      OH radicals. This work shows, for the first time, the application of combined
      HPLC with UV, MS, and NMR detection for complete structural elucidation of
      photocatalytic degradation products, and it will be of particular value in
      studies on the elimination of pollutants in aqueous solutions by photocatalysis.

PMID- 16642982
TI  - Direct sampling of chemical weapons in water by photoionization mass
      spectrometry.
AB  - The vulnerability of water supplies to toxic contamination calls for fast and
      effective means for screening water samples for multiple threats. We describe the
      use of photoionization (PI) mass spectrometry (MS) for high-speed, high
      throughput screening and molecular identification of chemical weapons (CW)
      threats and other hazardous compounds. The screening technology can detect a wide
      range of compounds at subacute concentrations with no sample preparation and a
      sampling cycle time of approximately 45 s. The technology was tested with CW
      agents VX, GA, GB, GD, GF, HD, HN1, and HN3, in addition to riot agents and
      precursors. All are sensitively detected and give simple PI mass spectra
      dominated by the parent ion. The target application of the PI MS method is as a
      routine, real-time early warning system for CW agents and other hazardous
      compounds in air and in water. In this work, we also present comprehensive
      measurements for water analysis and report on the system detection limits,
      linearity, quantitation accuracy, and false positive (FP) and false negative
      rates for concentrations at subacute levels. The latter data are presented in the
      form of receiver operating characteristic curves of the form of detection
      probability P(D) versus FP probability P(FP). These measurements were made using
      the CW surrogate compounds, DMMP, DEMP, DEEP, and DIMP. Method detection limits
      (3sigma) obtained using a capillary injection method yielded 1, 6, 3, and 2
      ng/mL, respectively. These results were obtained using 1-microL injections of
      water samples without any preparation, corresponding to mass detection limits of
      1, 6, 3, and 2 pg, respectively. The linear range was about 3-4 decades and the
      dynamic range about 4-5 decades. The relative standard deviations were generally
      <10% at CW subacute concentrations levels.

PMID- 16642983
TI  - Method for investigation of oligosaccharides from glycopeptides: direct
      determination of glycosylation sites in proteins.
AB  - Characterization of glycopeptides has become an important tool toward a better
      understanding of the molecular details in carbohydrate-protein interactions. In
      this approach, oligosaccharides are commonly not detectable under mass
      spectrometric conditions because of ionization suppression by deglycosylated
      peptides. Their composition is only deduced from the mass differences between
      glycopeptides and corresponding deglycosylated peptides. Here, we describe how
      carbohydrates can be easily detected in the PNGase-treated samples and
      structurally investigated next to the peptides. The efficacy of this method is
      demonstrated through the analysis of tryptic glycopeptides obtained from human
      IgG. Following deglycosylation with PNGaseF and derivatization with
      phenylhydrazine, MALDI spectra produced ion peaks of labeled oligosaccharides and
      deglycosylated peptides. The relative abundances of individual oligosaccharides
      were consistent with those of the glycopeptides. MALDI-MS/MS provided useful data
      for the structural elucidation of oligosaccharides, including the assignment of
      dominant isomers and glycosylation sites in peptides. MALDI-MS/MS fragmentation
      patterns of deglycosylated peptide ions indicated glycosylation sites at
      asparagine 297 and 299. The observed peptide of the composition ADQTVYR,
      described for the first time in this study, indicated new glycosylation sites in
      IgG1 human myeloma plasma.

PMID- 16642984
TI  - Continuous flow analytical microsystems based on low-temperature co-fired ceramic
      technology. Integrated potentiometric detection based on solvent polymeric ion
      selective electrodes.
AB  - In this paper, the low-temperature co-fired ceramics (LTCC) technology, which has
      been commonly used for electronic applications, is presented as a useful
      alternative to construct continuous flow analytical microsystems. This technology
      enables not only the fabrication of complex three-dimensional structures rapidly
      and at a realistic cost but also the integration of the elements needed to carry
      out a whole analytical process, such as pretreatment steps, mixers, and detection
      systems. In this work, a simple and general procedure for the integration of ion
      selective electrodes based on liquid ion exchanger is proposed and illustrated by
      using ammonium- and nitrate-selective membranes. Additionally, a screen-printed
      reference electrode was easily incorporated into the microfluidic LTCC structure
      allowing a complete on-chip integration of the potentiometric detection.
      Analytical features of the proposed systems are presented.

PMID- 16642985
TI  - Simultaneous extraction and fractionation of polycyclic aromatic hydrocarbons and
      their oxygenated derivatives in soil using selective pressurized liquid
      extraction.
AB  - In this study, a selective pressurized liquid extraction (PLE) method which can
      extract polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives
      (oxy-PAHs) from contaminated soil and simultaneously separate them into two
      fractions was developed. The method uses extraction cells packed with a
      chromatographic adsorbent and extraction solvents of increasing polarity. Several
      experiments were conducted on both spiked and authentic contaminated soil
      samples. Different types of adsorbents, combinations of extraction solvents, and
      extraction temperatures were tested in order to find a method that could fulfill
      the purpose of the study. The final method was based on extraction cells packed
      with 2% deactivated silica gel. The PAHs were extracted with
      cyclohexane/dichloromethane (9:1) at 120 degrees C, after which the oxy-PAHs
      where extracted with cyclohexane/dichloromethane (1:3) at 150 degrees C. The PAHs
      and oxy-PAHs were efficiently separated into two fractions, and only trace
      amounts of some compounds were found in the inappropriate fraction. The
      recoveries of the PAHs were mostly above 70% and of the oxy-PAHs, above 90%. The
      linearity of the method was good, and the calibration curves for most compounds
      had a regression coefficient better than 0.99 and an intercept close to the
      origin of coordinates. When the selective PLE method was applied to seven
      authentic soil samples, the results were found to be in good agreement with those
      of a reference method based on Soxhlet extraction and silica gel cleanup and also
      in good agreement with the certified reference values available for one of the
      soils. The selective PLE method is faster and consumes less solvent than a
      traditional method based on separate extraction and fractionation steps. The
      selective PLE method is, therefore, suitable for the concurrent analysis of PAHs
      and oxy-PAHs during large-scale soil contamination studies. This will provide
      more information about the soil contamination and the levels of toxicity than an
      ordinary PAH analysis.

PMID- 16642986
TI  - Internal calibrant in the stripping gas. An approach to calibration of membrane
      extraction with a sorbent interface.
AB  - A new technique for calibration in membrane extraction processes by adding an
      analytically noninterfering internal calibrant in the stripping gas is described.
      Membrane extraction with a sorbent interface (MESI) system was used to evaluate
      this method. During the membrane extraction process, the internal calibrant
      present in the carrier (stripping) gas and the target analyte present in the
      sample matrix will permeate simultaneously through the membrane in opposite
      directions. The changes of accumulation amounts of internal calibrant in the
      microtrap can be used as a means of calibration to correct the variations of
      extraction rate due to the variation in environmental factors, such as the sample
      velocity and the membrane temperature. Thus, this approach should allow for more
      accurate estimates of the concentrations of target analytes at various sampling
      or monitoring conditions during field analysis. Finally, a group of selected
      compounds was employed to test this calibration strategy, and the results
      indicated the advantages of the proposed approach for on-site analysis.

PMID- 16642987
TI  - Method for distinguishing specific from nonspecific protein-ligand complexes in
      nanoelectrospray ionization mass spectrometry.
AB  - A new methodology for distinguishing between specific and nonspecific protein
      ligand complexes in nanoelectrospray ionization mass spectrometry (nanoES-MS) is
      described. The method involves the addition of an appropriate reference protein
      (P(ref)), which does not bind specifically to any of the solution components, to
      the nanoES solution containing the protein(s) and ligand(s) of interest. The
      occurrence of nonspecific protein-ligand binding is monitored by the appearance
      of nonspecific (P(ref) + ligand) complexes in the nanoES mass spectrum.
      Furthermore, the fraction of P(ref) undergoing nonspecific ligand binding
      provides a quantitative measure of the contribution of nonspecific binding to the
      measured intensities of protein and specific protein-ligand complexes. As a
      result, errors introduced into protein-ligand association constants, K(assoc), as
      determined with nanoES-MS, by nonspecific ligand binding can be corrected. The
      principal assumptions on which this methodology is based, namely, that the
      fraction of proteins and protein complexes that engage in nonspecific ligand
      binding during the nanoES process is determined by the number of free ligand
      molecules in the offspring droplets leading to gaseous ions and is independent of
      the size and structure of the protein or protein complex, are shown to be
      generally valid. The application of the method for the determination of K(assoc)
      for two protein-carbohydrate complexes, under conditions where nonspecific ligand
      binding is prevalent, is demonstrated.

PMID- 16642988
TI  - Optical pH measurements with water dispersion of polyaniline nanoparticles and
      their redox sensitivity.
AB  - A new method for optical pH and redox measurements with a commercially available
      water dispersion of polyaniline (PANI) nanoparticles (mean particle size, 46 nm)
      is presented. The pH measurements are based on the acid-base equilibrium of PANI
      and were carried out either by combining both the automated sequential injection
      analysis (SIA) and UV-visible spectrophotometric techniques or with a fiber-optic
      light guide. In the former case, the detection was done in continuous mode at
      lambda = 800 nm by using the SIA technique for transporting the sample to a flow
      through cell, which was placed in the light path of the photometer. With the
      fiber-optic light guide, the detection was done in batch mode at lambda = 400 and
      580 nm. In both methods, fresh pH reagent (PANI) solution was used in each
      measurement, thus overcoming the problem with hysteresis (memory effect), which
      is usually observed with PANI films. The PANI nanoparticles were characterized
      with UV-visible spectroscopy in pH buffer solutions between pH 2-12 and a
      protonation constant of logK(0.5H,L)(H(0.5)L) = 4.4 was calculated from these
      data. Fast pH measurements can be done between pH 6 and 10.5 depending on the
      measuring technique. It is possible to determine pH with an accuracy of 0.1 pH
      unit between pH 8 and 10.5 (RSD, 0.5-2%). Redox transitions typical for PANI
      films were also observed for water solutions of PANI nanoparticles in the
      presence of the hexacyanoferrate(II/III) and the iron(II/III) oxalate redox
      couples. The absorbance at lambda = 875 nm is linearly dependent on the logarithm
      of the concentration ratio (0.1-10) of the iron oxalate redox couple.

PMID- 16642989
TI  - Gas chromatography-microchip atmospheric pressure chemical ionization-mass
      spectrometry.
AB  - An atmospheric pressure chemical ionization (APCI) microchip is presented for
      combining a gas chromatograph (GC) to a mass spectrometer (MS). The chip includes
      capillary insertion channel, stopper, vaporizer channel, nozzle and nebulizer gas
      inlet fabricated on the silicon wafer, and a platinum heater sputtered on a glass
      wafer. These two wafers are joined by anodic bonding creating a two-dimensional
      version of an APCI microchip. The sample from GC is directed via heated transfer
      line capillary to the vaporizer channel of the APCI chip. The etched nozzle forms
      narrow sample plume, which is ionized by an external corona discharge needle, and
      the ions are analyzed by a mass spectrometer. The GC-microchip APCI-MS
      combination provides an efficient method for qualitative and quantitative
      analysis. The spectra produced by microchip APCI show intensive protonated
      molecule and some fragmentation products as in classical chemical ionization for
      structure elucidation. In quantitative analysis the GC-microchip APCI-MS showed
      good linearity (r(2) = 0.9989) and repeatability (relative standard deviation
      4.4%). The limits of detection with signal-to-noise ratio of three were between
      0.5 and 2 micromol/L with MS mode using selected ion monitoring and 0.05
      micromol/L with MS/MS using multiple reaction monitoring.

PMID- 16642990
TI  - Enantiomeric separation using an l-RNA aptamer as chiral additive in partial
      filling capillary electrophoresis.
AB  - In this paper, we report the chiral resolution of arginine using an anti-arginine
      l-RNA aptamer chiral selector in partial-filling CE. The effects of the capillary
      temperature, sample load, and aptamer plug length on the enantiomeric separation
      were assessed. Very high chiral resolving capability was observed at low or
      moderate capillary temperatures (the target peak being not detected in the
      separation window), whereas the practical chiral resolution was achieved only at
      high enough temperatures (50-60 degrees C). Over this high-temperature range, the
      electrophoretic behavior of the target enantiomer appeared to result from a
      combination of binding site heterogeneity, slow desorption kinetics, and
      concentration overload of aptamer binding sites. From additional thermal UV
      melting experiments, three RNA conformations were identified for the 50-60
      degrees C temperatures. It was suggested that the presence of these different RNA
      conformations was a plausible source of the binding site heterogeneity.

PMID- 16642991
TI  - Biexponential fitting of diffusion-ordered NMR data: practicalities and
      limitations.
AB  - High resolution diffusion-ordered NMR spectroscopy (HR-DOSY) generally uses
      monoexponential fitting of the diffusional attenuation of pulsed-field gradient
      stimulated echo spectra and can, thus, only give proper separation of signals in
      the diffusion domain where the individual peaks are well-resolved in the spectral
      domain. In principle, it should be possible to resolve the decays of coincident
      spectral peaks by multiexponential fitting, but the well-known fundamental
      difficulties in such a separation are exacerbated by instrumental distortions of
      the signal decay. The limitations imposed on biexponential fitting by finite
      signal-to-noise ratio and by the distortion of the theoretical form of the signal
      attenuation as a result of pulsed-field gradient nonuniformity are explored, and
      the improvement in DOSY spectra produced using biexponential fitting afforded by
      compensating for the latter are illustrated.

PMID- 16642992
TI  - Development of a multibed sorption trap, comprehensive two-dimensional gas
      chromatography, and time-of-flight mass spectrometry system for the analysis of
      volatile organic compounds in human breath.
AB  - A method for the determination of volatile organic compounds (VOCs) at sub-trace
      levels in breath samples based on a multibed sorption trap for the collection and
      concentration of VOCs, a comprehensive multidimensional gas chromatograph (GCxGC)
      for the separation of complex mixtures, and a time-of-flight mass spectrometer
      detector is designed and developed. The good performance of the trap tube device
      developed for the concentration together with the high sensitivity and separation
      power of the GCxGC results in a powerful system. In the analysis of samples, more
      than 100 different compounds are detected of which between 65 and 85 are clearly
      identified. A total of approximately 250 different compounds are observed in all
      the samples evaluated of which 142 are identified. A preliminary study to
      evaluate breath biomarkers for active smoking is performed. The levels of
      previously described biomarkers are found to be strongly time-dependent with
      amounts found approximately 1 h after smoking returning to the levels found in
      nonsmoking volunteers. However, 2,5-dimethylfuran, 2-methylfuran, and furan are
      found to be effective biomarkers given that they were only found in samples taken
      from smokers and could still be detected more than 2 h after smoking.

PMID- 16642993
TI  - Fragmentation of protonated peptide ions via interaction with metastable atoms.
AB  - Fragmentation of protonated peptide ions via interaction with low kinetic energy
      electronicallyexcited metastable argon atoms was studied in a linear trap-time-of
      flight mass spectrometer. Metastable argon atoms were generated using a glow
      discharge-type source. Protonated peptide ions of substance P, bradykinin,
      fibrinopetide A, and insulin oxidized chain B were produced by electrospray
      ionization and trapped in a quadrupole ion guide for 100-400 ms. Intensive series
      of c- and z-ions were observed in all cases. The kinetic measurements of the
      fragmentation rates are consistent with calculations of the reaction cross
      section based on the Landau-Zener approximation.

PMID- 16642994
TI  - Characterizing the phospholipid profiles in mammalian tissues by MALDI FTMS.
AB  - Discussed here is an analytical method for profiling lipids and phospholipids
      directly from mammalian tissues excised from Mus musculus (house mouse).
      Biochemical analysis was accomplished through the use of matrix-assisted laser
      desorption/ionization (MALDI) Fourier transform mass spectrometry, where whole
      tissue sections of mouse brain, heart, and liver were investigated. Lipid and
      phospholipid ions create complex MALDI mass spectra containing multiple ions with
      different m/z values corresponding to the same fundamental chemical species. When
      a computational sorting approach is used to group these ions, the standard
      deviation for observed relative chemical abundance can be reduced to 6.02%.
      Relative standard deviations of 10% are commonly accepted for standard
      chromatographic phospholipid analyses. Average mass measurement accuracy for 232
      spectra representing three tissue types from 12 specimens was calculated to be
      0.0053 Da. Further it is observed, that the data and the analysis between all the
      animals have near-identical phospholipid contents in their brain, heart, and
      liver tissues, respectively. In addition to the need to accurately measure
      relative abundances of phospholipid species, it is essential to have adequate
      mass resolution for complete and accurate overall analysis. It is reasonable to
      make mass composition assignments with spectral resolving power greater than
      8000. However, results from the present study reveal 14 instances (C12 carbon
      isotope) of multiple m/z ions having the same nominal value that require greater
      resolution in order that overlap will not occur. Spectra measured here have an
      average resolving power of 12 000. It is established that high mass resolution
      and mass accuracy coupled with MALDI ionization provide for rapid and accurate
      phospholipid analysis of mammalian tissue sections.

PMID- 16642995
TI  - Double-hexahistidine tag with high-affinity binding for protein immobilization,
      purification, and detection on ni-nitrilotriacetic acid surfaces.
AB  - There is a particular need in protein analysis and purification for specific,
      functional, and generic methods of protein immobilization on solid supports. Here
      we describe a double-hexahistidine (His6) tag sequence, comprising two
      hexahistidines separated by an 11-amino acid spacer, which shows at least 1 order
      of magnitude stronger binding to Ni-NTA-modified surfaces than a conventional
      single-His6 tag or two single-His6 tags at N- and C-termini. Using, as a model,
      tagged versions of green fluorescent protein (GFP), stable and tight binding of
      the double-His6 tag/Ni-NTA interaction was demonstrated by competitive elution
      from Ni-NTA agarose beads, surface plasmon resonance on a Ni-NTA chip, and ELISA
      in Ni-NTA microwell plates. Protein purification by Ni-NTA chromatography was
      improved by a 6-8-fold increase in imidazole concentration required for elution,
      while the dissociation rate of double-His6 GFP from Ni-NTA chips in SPR (BIAcore)
      was 10 times slower than for single-His6-tagged proteins. ELISA assays and
      protein microarrays constructed with double-His6 GFP demonstrated greater
      detection sensitivity with anti-His antibodies and Ni-NTA conjugates. Moreover,
      the double-His6 tag could serve simultaneously both for protein immobilization
      and for detection on surfaces. The double-His6 peptide has the potential to be a
      universal tag for protein immobilization and detection on arrays and single-step
      purification of proteins from crude mixtures.

PMID- 16642996
TI  - Determination of 13C/12C carbon isotope ratio.
AB  - Isotopomers 12CO2 and 13CO2 absorbed into polystyrene films provide narrow,
      sharp, and well-resolved IR absorption bands for the nu3 antisymmetric stretching
      mode. This is exploited to set up an inexpensive FT-IR-based method for the
      measurement of the carbon isotope ratio. Accuracy of 2.5 per thousand delta13C
      units is readily achieved already at a low resolution of 2 cm(-1).

PMID- 16642997
TI  - Microfluidic single-cell mRNA isolation and analysis.
AB  - Single-cell gene expression analysis holds great promise for studying diverse
      biological systems, but methodology to process these precious samples in a
      reproducible, quantitative, and parallel fashion remains challenging. Here, we
      utilize microfluidics to isolate picogram and subpicogram mRNA templates, as well
      as to synthesize cDNA from these templates. We demonstrate single-cell mRNA
      isolation and cDNA synthesis, provide quantitative calibrations for each step in
      the process, and measure gene expression in individual cells. The techniques
      presented here form the foundation for highly parallel single-cell gene
      expression studies.

PMID- 16642998
TI  - High-throughput determination of quantitative structure-property relationships
      using a resonant multisensor system: solvent resistance of bisphenol a
      polycarbonate copolymers.
AB  - Polymers are important materials for sensor, microfluidic, and other demanding
      applications. High-throughput screening methodology has been applied for the
      evaluation of the solvent resistance of a family of polycarbonate copolymers
      prepared from the reaction of bisphenol A (BPA), hydroquinone (HQ), and
      resorcinol (RS) in different solvents of practical importance, such as
      chloroform, tetrahydrofuran (THF), and methyl ethyl ketone (MEK). We employed a
      24-channel acoustic-wave sensor system that provided previously unavailable
      capabilities for parallel evaluation of polymer solvent resistance. This high
      throughput polymer evaluation approach assisted in construction of detailed
      solvent-resistance maps of polycarbonate copolymers and in determination of
      quantitative structure-property relationships. The best absolute solvent
      resistance of all studied copolymers was achieved in MEK, followed by chloroform
      and THF. A D-optimal mixture design was employed to explore the relationship
      between the copolymer compositions and their solvent resistance. The applied
      special cubic model for each solvent took into account the primary mixture terms
      such as BPA, HQ, and RS; binary interaction terms such as BPA-HQ, BPA-RS, and HQ
      RS; and a ternary interaction term BPA-HQ-RS. A combination of the normal
      distribution of the model residuals and the very high values of adjusted R2 (0.97
      0.99) demonstrated a good quality of the model. At a HQ concentration of 40 mol
      %, the solvent resistance was the highest for all tested solvents, and different
      concentrations of BPA (40 and 60 mol %) and RS (0 and 20 mol %) did not affect
      the solvent resistance. Without HQ, solvent resistance was decreasing with an
      increase of RS and decrease of BPA. Overall, with an increase of HQ concentration
      from 0 to 40 mol %, the solvent resistance of BPA-HQ-RS copolymers was improved
      by up to 3 times in THF, by 21 times in chloroform, and by 32 times in MEK.

PMID- 16642999
TI  - Fluorescent approach to quantitation of reactive oxygen species in mainstream
      cigarette smoke.
AB  - A novel approach to monitoring of mainstream smoke reactive oxygen species (ROS)
      has been developed and applied to the quantitation of smoke oxidants. Redox
      active fluorescent probe dihydrorhodamine 6G (DHR-6G) was selected as the
      molecular probe because it is sensitive to typical smoke ROS. The experimental
      system couples an automatic cigarette smoke machine fiber-optic fluorometer for
      real-time monitoring of the reaction progress between cigarette smoke and DHR-6G.
      Quantitation was achieved based on the amount of rhodamine 6G, which is the sole
      product from DHR-6G oxidation. With the optimization of the trapping efficiency,
      we detected 391 nmol of ROS/cigarette in the mainstream CS for a standard
      cigarette 2R4F under standard Federal Trade Commission smoking protocol. Applying
      this method, we quantified the ROS of selected cigarettes and found that the
      cigarettes made of burley tobacco have much ( approximately 10 times) higher ROS
      content in the smoke than that in the tobacco made of bright tobacco. The
      smokeless cigarette, Eclipse, has comparable ROS with cigarettes made of bright
      tobacco.

PMID- 16643000
TI  - Determination of the structure and orientation of organic molecules tethered to
      flat graphitic carbon by ATR-FT-IR and Raman spectroscopy.
AB  - Mono- and multilayers of nitroazobenzene (NAB), azobenzene (AB), nitrobiphenyl
      (NBP), biphenyl (BP), and fluorene (FL) were covalently bonded to flat pyrolyzed
      photoresist films (PPF) by electrochemical reduction of their diazonium
      derivatives. The structure and orientation of the molecular layers were probed
      with ATR-FT-IR and Raman spectroscopy. A hemispherical germanium ATR element used
      with p-polarized light at 65 degrees incidence angle yielded high signal/noise IR
      spectra for monolayer coverage of molecules on PPF. The IR spectra are dominated
      by in-plane vibrational modes in the 1000-2000-cm(-1) spectral range but also
      exhibit weaker out-of-plane deformations in the 650-1000-cm(-1) region. The
      average tilt angle with respect to the surface normal for the various molecules
      varied from 31.0 +/- 4.5 degrees for NAB to 44.2 +/- 5.4 degrees for FL with AB,
      NBP, and BP exhibiting intermediate adsorption geometries. Raman intensity ratios
      of NAB and AB for p- and s-polarized incident light support the conclusion that
      the chemisorbed molecules are in a predominantly upright orientation. The results
      unequivocally indicate that molecules electroreduced from their diazonium
      precursors are not chemisorbed flat on the PPF surface, but rather at an angle,
      similar to the behavior of Au/thiol self-assembled monolayers, Langmuir-Blodgett
      films, and porphyrin molecules chemisorbed thermally on silicon and PPF from
      alkyne and alkene precursors.

PMID- 16643001
TI  - Determination of the synthetic origin of methamphetamine samples by 2H NMR
      spectroscopy.
AB  - Samples of methamphetamine, prepared according to the most common synthetic
      pathways, were submitted to natural-abundance 2H NMR spectroscopy. The deuterium
      content at the various sites of the molecule was found to depend on its synthetic
      history. The technique provides a chemical fingerprint of methamphetamine samples
      and can give hints to trace back the starting materials and the synthetic
      procedures.

PMID- 16643002
TI  - Microarray glass slides coated with block copolymer brushes obtained by
      reversible addition chain-transfer polymerization.
AB  - The reversible addition-fragmentation chain-transfer polymerization was used to
      prepare microarray slides grafted with polymer brushes for DNA-based
      applications. Block copolymer brushes of N,N-dimethylacrylamide (DMA) and
      glycidyl methacrylate (GMA), poly(DMA-b-GMA) were prepared by extending living
      poly(dimethylacrylamide) chains. The functional surface was used as a substrate
      for oligonucleotide hybridization experiments. The results were compared to those
      provided by glass slides coated by a self-assembled monolayer made of (3
      glycidyloxypropyl)trimethoxysilane. Surfaces coated with block polymer brushes
      bearing oxirane groups are more efficient as substrates for oligonucleotide
      hybridization than surfaces coated with nonpolymeric self-assembled monolayers
      containing the same functional group. The high probe grafting density and
      hybridization efficiency achieved with this polymeric coating reveal the
      importance of the block architecture to ensure good accessibility of the
      immobilized probe. The new surface was characterized by static angle measurements
      and diffuse reflectance FT-IR spectroscopy on a silica model system.

PMID- 16643003
TI  - Development of a NIST standard reference material containing thirty volatile
      organic compounds at 5 nmol/mol in nitrogen.
AB  - Primary gravimetric gas cylinder standards containing 30 volatile organic
      compounds (VOCs) in nitrogen were prepared using a procedure previously developed
      to prepare gas mixture cylinder standards of VOCs at the 5 nmol/mol level. This
      set of primary standards was intercompared to existing gas cylinder standards,
      containing as many as 19 of the 30 volatile organics present in these new
      primaries, using gas chromatography with a hydrogen flame ionization detector
      coupled with cryogenic preconcentration. The linear regression analysis showed
      excellent agreement among the standards for each compound. Similar mixtures
      containing many of these compounds in treated aluminum gas cylinders have been
      evaluated over time and have shown stability for as much as 10 years. The
      development of these 30-component primary standards led to the preparation and
      certification of a reissue of Standard Reference Material (SRM) 1804 at the
      nominal amount-of-substance fraction of 5 nmol/mol for each analyte. A lot of 20
      cylinders containing the mixture was prepared at NIST following previously
      demonstrated protocols for preparation of the cylinders. Each cylinder was
      analyzed against one cylinder from the lot, designated as the "lot standard," for
      each of the 30 compounds. As a result of the uncertainty analysis, the data
      showed that rather than declaring the lot homogeneous with a much higher
      uncertainty, each cylinder could be individually certified. The expanded
      uncertainty limits ranged from 1.5 to 10% for 28 of the 30 analytes, with two of
      the analytes having uncertainties as high as 19% in those SRM cylinders
      certified. Due to stability issues and some high uncertainties for a few analytes
      in 2 of the samples, 18 of the 20 candidate SRM samples were certified. These
      volatile organic gas mixtures represent the most complex gas SRMs developed at
      NIST.

PMID- 16643004
TI  - Direct measurement of free chloride concentrations in the phagolysosomes of human
      neutrophils.
AB  - Human neutrophils synthesize hypochlorous acid, a nonradical oxidant, as one of
      the antimicrobial agents to kill phagocytosed pathogens within phagolysosomes.
      The production of HOCl is catalyzed by myeloperoxidase using chloride anions (Cl
      ). Even though various approaches have been documented to measure cytosolic Cl-
      concentrations, direct detection of phagolysosomal free Cl- in a real-time
      fashion is not available. Here we report the development of a new dual-labeled
      fluorescent probe by conjugation of the chloride-sensitive 6-methoxyquinoline and
      chloride-insensitive tetramethylrhodamine to the zymosan particles. On the
      surface of the zymosan particles, the chloride-sensitive fluorophore responded
      linearly to chloride concentrations when plotted according to the Stern-Volmer
      collisional quenching equation and the chloride-insensitive fluorophore served as
      an internal reference. After phagocytosis into neutrophils, the probe was able to
      monitor intraphagosomal chloride levels authentically. Human neutrophils in the
      medium containing 122 mM chloride had a phagolysosomal chloride level of 73.3 +/-
      12.2 mM (N = 5). In contrast, the neutrophils in a chloride-free isoosmotic
      medium had a chloride level of 6.6 +/- 1.9 mM (N = 5) in the phagolysosomal
      compartment. These data clearly demonstrated that the extracellular chloride
      levels affect intraphagolysosomal chloride levels in human neutrophils. Moreover,
      when the extracellular chloride concentration was switched from high level (122
      mM) to low level (0 mM) or vice versa, the probe demonstrated complete
      reversibility. The data indicate that the new zymosan-conjugated chloride probe
      described here can be used as an indicator for measurement of the free chloride
      level within the phagolysosomes of neutrophils and other phagocytic cell types.

PMID- 16643005
TI  - Redox enzymes immobilized on electrodes with solution cosubstrates. General
      procedure for simulation of time-resolved catalytic responses.
AB  - In view of the existing and potential applications of electrochemical enzymatic
      catalysis with redox enzymes immobilized on the electrode surface in biosensors,
      a numerical calculation procedure for simulating their cyclic voltammetric
      responses is presented. It is applicable to systems involving a redox cosubstrate
      in solution. The cosubstrates, substrates, products, and inhibitors are assumed
      to diffuse linearly (planar electrode) between the electrode and the solution.
      The reactions in which the various forms of the immobilized enzyme participate
      may be as numerous and intricate as required by the simulation with no other
      restriction than the computing time. They may, at will, follow or not follow
      Michaelis-Menten kinetics. Slow charge-transfer cosubstrates are treated in the
      framework of Butler-Volmer kinetic law.

PMID- 16643006
TI  - Detection of antigens in biologically complex fluids with photografted whole
      antibodies.
AB  - A highly sensitive (pM), efficient (t < 20 min) detection assay was developed by
      designing surfaces with grafted antibodies. Through this approach, a short half
      life antigen, glucagon, was rapidly detected in a biologically complex
      plasma/blood environment. Tailoring of graft composition eliminates the need for
      time-consuming blocking steps, significantly reducing antigen-antibody incubation
      times, while maintaining antibody specificity and activity toward target antigen.
      Grafted antibodies were bound through solvated, mobile polymer chains, thereby
      circumventing problems associated with antibody accessibility, analyte diffusion,
      and steric limitations. The efficiency of this assay is provided through grafting
      synthesized, acrylated antibodies in the presence of PEG monoacrylate. This
      procedure eliminates the need for blocking steps, due to a decrease in
      nonspecific protein interactions. These polymerizable antibodies were tethered
      with a range of densities while retaining biological activity. Moreover,
      biological activity of acrylated antibodies was compared to that of unmodified
      antibodies and remained comparable. The acrylated antibodies were grafted from
      substrate surfaces using controlled radical photopolymerization, maintaining the
      advantages of classical antibody immobilization techniques while providing
      improved detection. Through integrating this antibody conjugation chemistry and
      immunoassay approach with photolithographic techniques, construction of spatial
      patterns on a microfluidic device was demonstrated for efficient, parallel
      screening of multiple antigens.

PMID- 16643007
TI  - Strong overtones and combination bands in ultraviolet resonance Raman
      spectroscopy.
AB  - Ultraviolet resonance Raman spectroscopy is carried out using a continuous wave
      frequency-doubled argon ion laser operated at 229, 244, and 257 nm in order to
      characterize the overtones and combination bands for several classes of organic
      compounds in liquid solutions. Contrary to what is generally anticipated, for
      molecules such as pyrene and anthracene, strong overtones and combination bands
      can show up; it is demonstrated that their intensity depends critically on the
      applied laser wavelength. If the excitation wavelength corresponds with a purely
      electronic transition--this applies to a good approximation for 244-nm excitation
      in the case of pyrene and for 257-nm excitation in the case of anthracene--mostly
      fundamental vibrations (up to 1700 cm(-1)) are observed. Overtones and
      combination bands are detected but are rather weak. However, if the laser
      overlaps with the vibronic region--as holds for 229- and 257-nm excitation for
      pyrene and 244-nm excitation for anthracene--very strong bands are found in the
      region 1700-3400 cm(-1). As illustrated for pyrene at 257 nm, all these bands can
      be assigned to first overtones or binary combinations of fundamental vibrations.
      Their intensity distribution can roughly be simulated by multiplying the relative
      intensities of the fundamental bands. Significant bands can also be found in the
      region 3400-5000 cm(-1), corresponding with second overtones and ternary
      combinations. It is shown that these findings are not restricted to planar and
      rigid molecules with high symmetry. Substituted pyrenes exhibit similar effects,
      and relatively strong overtones are also observed for adenosine monophosphate and
      for abietic acid. The reasons for these observations are discussed, as well as
      the potential applicability for analytical purposes.

PMID- 16643008
TI  - Single-nucleotide polymorphism genotyping by nanoparticle-enhanced surface
      plasmon resonance imaging measurements of surface ligation reactions.
AB  - A sensitive method for the analysis of single nucleotide polymorphisms (SNPs) in
      genomic DNA that utilizes nanoparticle-enhanced surface plasmon resonance imaging
      (SPRI) measurements of surface enzymatic ligation reactions on DNA microarrays is
      demonstrated. SNP identification was achieved by using sequence-specific surface
      reactions of the enzyme Taq DNA ligase, and the presence of ligation products on
      the DNA microarray elements was detected using SPRI through the hybridization
      adsorption of complementary oligonucleotides attached to gold nanoparticles. The
      use of gold nanoparticles increases the sensitivity of the SPRI so that single
      bases in oligonucleotides can be successfully identified at a concentration of 1
      pM. This sensitivity is amply sufficient for performing multiplexed SNP
      genotyping by using multiple PCR amplicons and should also allow for the direct
      detection and identification of SNP sequences from 1 pM unamplified genomic DNA
      samples with this array-based and label-free SPRI methodology. As a first example
      of SNP genotyping, three different human genomic DNA samples were screened for a
      possible point mutation in the BRCA1 gene that is associated with breast cancer.

PMID- 16643009
TI  - Site selectively templated and tagged xerogels for chemical sensors.
AB  - We report on a new sensor strategy that we have termed site selectively templated
      and tagged xerogels (SSTTX). The SSTTX platform is completely self-contained, and
      it achieves analyte recognition without the use of biomolecules. To illustrate
      the SSTTX scheme's potential, we present results for the selective detection and
      quantification of a model compound, 9-anthrol. The first-generation SSTTX shows
      the following: (i) exhibits an apparent dissociation constant of (1.8 +/- 0.3) x
      10(-4) M for 9-anthrol; (ii) provides 0.3 muM detection limits for 9-anthrol;
      (iii) yields a 45-s response time (2-mum-thick film); (iv) is completely
      reversible (6% relative standard deviation after 25 cycles); (v) yields a
      selectivity factor for 9-anthrol over several structurally similar
      analogues/interferences (e.g., anthracene, 9,10-anthracenediol, benzophenone, 2
      naphthol, phenol, and pyrene) of between 290 and 520; and (vi) is stable (<2%
      drift in performance) for at least 10 months when stored under ambient conditions
      in the dark. The results also suggest SSTTXs as new sensor elements for
      glycoside, pharmaceutical, prostaglandin, and steroid sensors.

PMID- 16643010
TI  - Selection of smart aptamers by methods of kinetic capillary electrophoresis.
AB  - We coin the term "smart aptamers" -- aptamers with predefined binding parameters
      (k(on), k(off), Kd) of aptamer-target interaction. Aptamers, in general, are
      oligonucleotides, which are capable of binding target molecules with high
      affinity and selectivity. They are considered as potential therapeutic targets
      and also thought to rival antibodies in immunoassay-like analyses. Aptamers are
      selected from combinatorial libraries of oligonucleotides by affinity methods.
      Until now, technological limitations have precluded the development of smart
      aptamers. Here, we report on two kinetic capillary electrophoresis techniques
      applicable to the selection of smart aptamers. Equilibrium capillary
      electrophoresis of equilibrium mixtures was used to develop aptamers with
      predefined equilibrium dissociation constants (Kd), while nonequilibrium
      capillary electrophoresis of equilibrium mixtures facilitated selection of
      aptamers with different dissociation rate constants (k(off)). Selections were
      made for MutS protein, for which aptamers have never been previously developed.
      Both theoretical and practical aspects of smart aptamer development are
      presented, and the advantages of this new type of affinity probes are described.

PMID- 16643011
TI  - In situ measurement of Cl- concentrations and pH at the reinforcing
      steel/concrete interface by combination sensors.
AB  - This paper presents an in situ, nondestructive method of monitoring Cl-
      concentrations and pH values at the steel/concrete interface. The Ag/AgCl
      electrodes prepared by the electrochemical anodization and the Ir/IrO2 electrodes
      prepared by thermal oxidation in carbonate served as Cl- concentration and pH
      sensors, respectively. The potentiometric response of the Ag/AgCl electrode to
      the logarithm of Cl- concentrations ranging from 1 x 10(-4) to 2 M in saturated
      Ca(OH)2 solution simulating the inner electrolytic medium of concrete shows good
      linearity. The Ir/IrO2 electrode also exhibits an ideal Nernstian response in the
      range of pH 1-14. The Ag/AgCl and Ir/IrO2 electrodes were combined into a
      multiplex Cl-/pH sensor, and the sensor was embedded in concrete close to the
      steel/concrete interface to realize an in situ and long-term measurement of Cl-
      concentrations and pH values. The results indicate that the combined sensor is
      robust and sensitive enough to in situ measure Cl- concentrations and pH
      quantitatively at the steel/concrete interface, which is of indispensable
      importance to the study of corrosion and protection of the steel in concrete.

PMID- 16643012
TI  - Universal response in liquid chromatography using charged aerosol detection.
AB  - A new, empirical approach is introduced to correct for the varying response of
      aerosol-based detectors with the varying composition of the mobile phase during
      gradient elution in HPLC. A Corona charged aerosol detector was used in the
      experiments. The detector is characterized by a nearly universal response at a
      given, constant mobile-phase composition for sufficiently nonvolatile analytes. A
      second pump was used to deliver an exactly inverse gradient compared to the
      analytical HPLC system, and both flows were mixed in a tee piece before
      introduction to the Corona detector. The approach proposed made it possible to
      extend the universal response from isocratic to gradient elution conditions in
      HPLC, vastly improving the usefulness of this detection technique. The constant
      response of the detector obtained in this way was first demonstrated in flow
      injection analysis. Very similar calibration curves were obtained for six
      sulfonamide drugs after mobile-phase compensation. The approach was also applied
      to gradient elution with excellent results. The data were characterized by good
      precision ranging from 4% RSD at 10 mg/L to 1.6% RSD at 780 mg/L. The average
      limit of detection with a 2-microL injection was 0.5 mg/L, corresponding to 1 ng
      injected on the column. The approach proposed allows quantification of unknown
      compounds, e.g., in pharmaceutical mixtures. Measurement of analytes at a
      relative concentration of 0.05% versus the main component is demonstrated.

PMID- 16643013
TI  - Fluorescence monitoring of ATP-stimulated, endothelium-derived nitric oxide
      production in channels of a poly(dimethylsiloxane)-based microfluidic device.
AB  - Intracellular nitric oxide (NO) production in a microfluidic endothelium is
      detected using fluorescence microscopy. Bovine pulmonary artery endothelial cells
      (bPAECs) were loaded with the fluorescence probe diaminodifluorofluorescein
      diacetate (DAF-FM DA), and the subsequent fluorescent DAF-FM DA/NO adduct was
      measured. Solutions of bradykinin, a well-known stimulus of endothelium-derived
      NO, activated nitric oxide synthase (NOS) in the immobilized bPAECs. This
      activation was inhibited using l-nitro arginine methyl ester (L-NAME), a
      competitive inhibitor of NOS. Importantly, the NO production was also stimulated
      with adenosine triphosphate (ATP) using concentrations as low as 1 microM.
      Previous reports on stimulating NO production using an immobilized endothelium in
      microfluidic channels were limited by the requirement of ATP concentrations of at
      least 100 microM, a value that is not physiologically relevant. The ability to
      monitor NO production with ATP concentrations that are similar to in vivo levels
      of ATP in the microcirculation represents a major advance in the use of
      microfluidic technology as an in vitro model of the microcirculation.

PMID- 16643014
TI  - Direct-write fabrication of functional protein matrixes using a low-cost Q
      switched laser.
AB  - We report the use of an inexpensive, small, and "turn-key" Q-switched 532-nm
      Nd:YAG laser as a source for nonlinear, direct-write protein microfabrication. In
      this approach, microJoule pulses (pulse widths, approximately 600 ps) are focused
      using high numerical aperture optics to submicrometer focal spots, creating
      instantaneous intensities great enough to promote multiphoton excitation of a
      photosensitizer and subsequent intermolecular cross-linking of protein molecules.
      By scanning the femtoliter focal volume through reagent solution, extended
      protein-based structures can be fabricated with precise, three-dimensional
      topographies. As with earlier studies using a femtosecond titanium:sapphire laser
      costing more than 100K, physically robust and chemically responsive
      microstructures can be fashioned rapidly with feature sizes smaller than 0.5
      microm, and cross-linking can be achieved using both biologically benign
      sensitizers (e.g., flavins) and by using the proteins themselves to sensitize
      cross-linking. We demonstrate in situ fabrication to corral neurite outgrowth and
      show the ability to functionalize avidin structures with biotinylated reagents,
      an approach that enables chemical sensing to be performed in specified
      microenvironments. Characterization of this inexpensive, low-power source will
      greatly broaden access to direct-write protein microfabrication.

PMID- 16643015
TI  - Application of capture-recapture models to estimation of protein count in MudPIT
      experiments.
AB  - MudPIT is an automated shotgun proteomics approach that enhances the separation
      of peptides for sequencing by mass spectrometry analysis.We here adapt a
      mathematical model from ecology, namely, the capture-recapture model with a
      closed population and time-varying and heterogeneous individual probabilities of
      capture, to model the number of peptide identifications across the various cycles
      of a typical MudPIT experiment. In the absence of any prior information on
      abundance levels, the model can be used to estimate the total number of proteins
      in the experimental sample. We apply the model to a recent MudPIT-based
      experiment to estimate the total number of rat lung endothelial cell surface
      proteins. The model provides some practical guidelines for planning MudPIT
      experiments.

PMID- 16643016
TI  - Alternately pulsed nanoelectrospray ionization/atmospheric pressure chemical
      ionization for ion/ion reactions in an electrodynamic ion trap.
AB  - The alternate operation of nanoelectrospray ionization and atmospheric pressure
      chemical ionization, using a common atmosphere/vacuum interface and ion path, has
      been implemented to facilitate ion/ion reaction experiments in a linear ion trap
      based tandem mass spectrometer. The ion sources are operated in opposite polarity
      modes whereby one of the ion sources is used to form analyte ions while the other
      is used to form reagent ions of opposite polarity. This combination of ion
      sources is well-suited to implementation of experiments involving multiply
      charged ions in reaction with singly charged ions of opposite polarity. Three
      analytically useful ion/ion reaction types are illustrated: the partial
      deprotonation of a multiply protonated protein, the partial protonation of a
      multiply deprotonated oligonucleotide, and electron transfer to a multiply
      protonated peptide. The approach described herein is attractive in that it
      enables both single proton-transfer and single electron-transfer ion/ion reaction
      experiments to be implemented without requiring major modifications to the tandem
      mass spectrometer hardware. Furthermore, a wide range of reactant ions can be
      formed with these ionization methods and the pulsed nature of operation appears
      to lead to no significant compromise in the performance of either ion source.

PMID- 16643017
TI  - High-throughput single-cell analysis for enzyme activity without cytolysis.
AB  - A novel high-throughput method without cytolysis for determination of enzyme
      activity inside single cells was developed by a combination of chemical cell
      perforation and an intracellular enzyme-catalyzed reaction. Peroxidase (PO)
      inside human neutrophils was chosen as the model system. Cells were perforated
      with digitonin to form micropores on the cell membrane. The perforated cells,
      with physiological buffer saline of pH 7.4 containing hydroquinone (H2Q) and
      H2O2, were continuously propelled by pressure through a capillary as the
      microsampler and microreactor. Small molecules H2Q and H2O2 could diffuse into
      the cell interior through the micropores on the cell membrane, and the large
      molecule PO remained in the cell interior. Intracellular PO converted H2Q into
      benzoquinone (BQ). BQ diffused out from the cell interior to the cell surface
      through the micropores and formed a BQ zone around the cell. The process
      proceeded in the capillary during cell movement. The BQ zones around every moving
      perforated cell were continuously delivered to the capillary outlet by hydraulic
      flow and detected. An average detection rate of >1 cell/min was obtained.

PMID- 16643018
TI  - Discovery of a significant optical chromatographic difference between spores of
      Bacillus anthracis and its close relative, Bacillus thuringiensis.
AB  - A significant difference between two closely related Bacillus spores has been
      discovered using optical chromatography. This difference can be harnessed for the
      separation of microscopic particles using opposing laser and fluid flow forces.
      Particles of different size, composition, and shape experience different optical
      and fluid forces and come to rest at unique equilibrium positions where the two
      forces balance. Separations in excess of 600 mum have been observed between
      Bacillus anthracis Sterne strain and its genetic relative, Bacillus
      thuringiensis. These findings open new possibilities for detection and
      characterization of the biological warfare agent, B. anthracis, the causative
      agent of anthrax, the deadly mammalian disease. The large optical separation
      between these species is surprising given their close genetic relationship but
      may be explained by differences in their shape and exosporium morphology, which
      may result in differences in fluid drag force. The observation of large
      differences due to less common variables indicates the complex nature of the
      force balance in optical chromatography, which may in the future be used to
      separate and characterize microbiological samples. In general, the discovery of
      such large differences between such closely related biological species suggests
      new possibilities for the separation and characterization of microorganisms using
      the full range of emerging techniques that employ radiation pressure (optical
      filtering, laser tweezers, optical chromatography, etc.).

PMID- 16643019
TI  - Discovering new natural products directly from crude extracts by HPLC-SPE-NMR:
      chinane diterpenes in Harpagophytum procumbens.
AB  - HPLC-SPE-NMR experiments with crude extracts of Harpagophytum procumbens allowed
      the rapid identification of novel, unstable chinane-type tricyclic diterpenes (1
      and 2), along with numerous other constituents. Dramatic sensitivity gains
      achieved with this novel hyphenated technique establish a new paradigm in natural
      products research: rapid and rigorous structure determination of multiple extract
      components, including minor components, without preparative-scale isolation.

PMID- 16643020
TI  - Sesquiterpene lactones from Inula britannica and their cytotoxic and apoptotic
      effects on human cancer cell lines.
AB  - Three new sesquiterpenes (1-3), together with four known sesquiterpene lactones,
      were isolated from the flowers of Inula britannica var. chinensis. Structures
      were established on the basis of high-field 1D and 2D NMR methods supported by
      HRMS. All sesquiterpene lactones were tested for cytotoxicity as well as
      apoptotic ratio in human COLO 205, HT 29, HL-60, and AGS cancer cells. Compounds
      3 and 4, two alpha-methylene gamma-lactone-bearing sesquiterpenes, were modestly
      active in these assays.

PMID- 16643021
TI  - Serotonergic activity-guided phytochemical investigation of the roots of Angelica
      sinensis.
AB  - Serotonin receptor (5-HT(7)) binding assay-directed fractionation of a methanol
      extract of the dried roots of Angelica sinensis led to the isolation and
      identification of 21 compounds including a new phenolic ester, angeliferulate
      (1), and three new phthalides, 10-angeloylbutylphthalide (2), sinaspirolide (3),
      and ansaspirolide (4), along with 17 known compounds, p-hydroxyphenethyl trans
      ferulate (5), Z-ligustilide (6), Z-butylidenephthalide (7), senkyunolide I (8), Z
      6-hydroxy-7-methoxydihydroligustilide (9), N-butylbenzenesulfonamide (10),
      11(S),16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1-yl acetate (11), (3R,8S)
      falcarindiol (12), heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diol (13), oplopandiol
      (14), 8-hydroxy-1-methoxy-, Z-9-heptadecene-4,6-diyn-3-one (15), imperatorin,
      ferulic acid, vanillin, stigmasterol, sucrose, and 1,3-dilinolenin. This is the
      first report of a sulfonamide (10) identified from a higher plant source,
      although its presence needs further investigation. Biosynthetic pathways for
      dimeric phthalides 3 and 4 are proposed. Compounds 5, 7, 11, 12, 15, and
      imperatorin exhibited affinity toward 5-HT(7) receptors in a competitive binding
      assay.

PMID- 16643022
TI  - Capisterones A and B, which enhance fluconazole activity in Saccharomyces
      cerevisiae, from the marine green alga Penicillus capitatus.
AB  - A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress
      Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural
      product extracts for reversal of fluconazole resistance. The tropical green alga
      Penicillus capitatus was selected for bioassay-guided isolation, leading to the
      identification of capisterones A and B (1 and 2), which were recently isolated
      from this alga and shown to possess antifungal activity against the marine
      pathogen Lindra thallasiae. Current work has assigned their absolute
      configurations using electronic circular dichroism and determined their preferred
      conformations in solution based on detailed NOE analysis. Compounds 1 and 2
      significantly enhanced fluconazole activity in S. cerevisiae, but did not show
      inherent antifungal activity when tested against several opportunistic pathogens
      or cytotoxicity to several human cancer and noncancerous cell lines (up to 35
      microM). These compounds may have a potential for combination therapy of fungal
      infections caused by clinically relevant azole-resistant strains.

PMID- 16643023
TI  - Bioassay for the identification of natural product-based activators of peroxisome
      proliferator-activated receptor-gamma (PPARgamma): the marine sponge metabolite
      psammaplin A activates PPARgamma and induces apoptosis in human breast tumor
      cells.
AB  - Peroxisome proliferator-activated receptors (PPARs), members of the nuclear
      hormone receptor (NHR) family, are ligand-activated transcription factors.
      Ligands (agonists) of PPARgamma have been shown to inhibit growth, promote
      terminal differentiation, and induce apoptosis in human breast tumor cells. A
      cell-based reporter assay was developed to examine extracts of terrestrial and
      marine organisms for the ability to activate PPARgamma. Bioassay-guided
      fractionation and isolation of an active extract from Pseudoceratina rhax yielded
      the known histone deacetylase (HDAC) inhibitor psammaplin A (1). Compound 1
      activates PPARgamma in a MCF-7 cell-based reporter assay and induces apoptosis in
      human breast tumor cells in vitro. Molecular modeling studies suggest that 1 may
      interact with binding sites within the PPARgamma ligand-binding pocket.
      Therefore, in addition to its known effects on HDAC-mediated processes,
      activation of PPARgamma-regulated gene expression may play a role in the ability
      of 1 to induce apoptosis.

PMID- 16643024
TI  - Daphniyunnines A-E, alkaloids from Daphniphyllum yunnanense.
AB  - The first chemical study on the stems and leaves of Daphniphyllum yunnanense led
      to the isolation of five new alkaloids, daphniyunnines A-E (1-5). Daphniyunnines
      B-E (2-5) are four unusual C-22 nor-Daphniphyllum alkaloids. The structures of
      these alkaloids were characterized by spectroscopic methods, especially 2D NMR
      techniques. A single-crystal X-ray diffraction analysis was used to confirm the
      structure of 1. Daphniyunnine D (4) showed cytotoxicity against two tumor cell
      lines, P-388 and A-549, with IC(50) values of 3.0 and 0.6 microM, respectively.

PMID- 16643025
TI  - Sensitivity of cardiac background inward rectifying K+ outward current (IK1) to
      the alkaloids lepadiformines A, B, and C.
AB  - Three marine alkaloids, purified from Clavelina moluccensis, were structurally
      identified as lepadiformines A, B, and C and studied on frog atrial myocytes
      I(K1), using the patch-clamp technique. Lepadiformine A (0.4 to 3.3 microM)
      blocked I(K1) dose-dependently with an apparent dissociation constant (K(D))
      equal to 1.42 microM and a stoichiometry of 0.77. The block is voltage-dependent,
      suggesting that lepadiformine A occupies a receptor site located at about two
      thirds of the membrane depth. The shortening of the aliphatic chain at position
      C13 of lepadiformine B decreased the potency of the molecule to block I(K1) but
      not the affinity (K(D) = 1.56 microM) and stoichiometry (0.72). Additional
      deletion of the oxygenated side chain at C2 in lepadiformine C markedly decreased
      the inhibitory effect of the molecule. In conclusion, lepadiformine modulates
      I(K1) response in cardiac muscle. The oxygenated side chain in C2 is implicated
      in the affinity of lepadiformine, which behaved as an amine, for a receptor
      located near or inside the I(K1) pore, and the aliphatic chain length at position
      C13 is involved in the degree of I(K1) blockage.

PMID- 16643026
TI  - A new route toward 7-Oxo-13-hydroxy-8,11,13-podocarpatrienes from labdane
      diterpenes.
AB  - Trinorlabdane 1,5-diketones (7, 10a,b, 13a,b), which are easily prepared from
      labdane diterpenes, are directly converted into the corresponding 7-oxo-13
      hydroxy-8,11,13-podocarpatrienes, immediate precursors of bioactive compounds,
      under basic treatment. Utilizing this strategy, the first enantiospecific
      synthesis of 13-hydroxy-8,11,13-podocarpatriene (20), a constituent of Taiwania
      cryptomerioides, was achieved starting from (-)-sclareol (5) after a seven-step
      sequence in 55% overall yield.

PMID- 16643027
TI  - Cytotoxic oxylipins from a marine sponge Topsentia sp.
AB  - By a bioactivity-guided fractionation, seven new oxylipins, topsentolides A(1)
      C(2) (1-7), were isolated from the MeOH extract of a marine sponge Topsentia sp.
      Detailed NMR and MS analyses established the planar structures of these
      structurally related oxylipins, which are proposed to be biosynthesized by
      lipoxygenation followed by cyclization of unsaturated fatty acids. Acetonide
      derivatives and MTPA esters were prepared to elucidate the stereochemistry of
      topsentolides B(1) (3), B(2) (4), and C(2) (7). All compounds were tested against
      a panel of five human solid tumor cell lines and displayed moderate cytotoxicity.

PMID- 16643028
TI  - Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the
      marine cyanobacterium Lyngbya majuscula.
AB  - Cytotoxicity-guided fractionation of a strain of the marine cyanobacterium
      Lyngbya majuscula collected from Papua New Guinea led to the isolation of
      aurilides B (1) and C (2). The planar structures of 1 and 2 were established by
      spectroscopic analysis, including HR-FABMS, 1D (1)H and (13)C NMR, and 2D COSY,
      HSQC, HSQC-TOCSY, and HMBC spectra. The absolute configuration was determined by
      spectroscopic analysis and chiral HPLC analysis of acid hydrolysates of 1 and 2.
      Both aurilides B and C showed in vitro cytotoxicity toward NCI-H460 human lung
      tumor and the neuro-2a mouse neuroblastoma cell lines, with LC(50) values between
      0.01 and 0.13 microM. Aurilide B (1) was evaluated in the NCI 60 cell line panel
      and found to exhibit a high level of cytotoxicity (the mean panel GI(50)
      concentration was less than 10 nM) and to be particularly active against
      leukemia, renal, and prostate cancer cell lines.

PMID- 16643029
TI  - DNA methyl transferase inhibiting halogenated monoterpenes from the Madagascar
      red marine alga Portieria hornemannii.
AB  - Three new halogenated monoterpenes, 2, 3, and 4, along with the known compounds
      halomon (1) and two analogues, 5 and 6, were isolated from the Madagascar red
      marine alga Portieria hornemannii. The structures of all three new compounds were
      determined by NMR spectroscopy in combination with mass spectrometric data
      analysis. Two of these monoterpenes (1 and 2) were low micromolar inhibitors of
      DNA methyl transferase-1.

PMID- 16643030
TI  - Metabolites from the marine-derived fungus Chromocleista sp. isolated from a deep
      water sediment sample collected in the Gulf of Mexico.
AB  - As part of our ongoing chemical investigation of biologically active metabolites
      from marine fungi, three new compounds, p-hydroxyphenopyrrozin (1) and
      diketopiperazines (3, 4), have been isolated from the marine-derived fungus
      Chromocleista sp. In addition, the fungus gave the known compound phenopyrrozin
      (2), four known diketopiperazines (6-9), N-acetyltryptamine (10), and agathic
      acid (11). Another new diketopiperazine (5) was separated and identified as a
      decomposition product of 3 and 4. The structures of the new metabolites were
      determined on the basis of mass spectroscopy, NMR experiments, and derivatization
      methods. The absolute configuration of 1 was determined by X-ray crystallography
      studies.

PMID- 16643031
TI  - Antibacterial, partially acetylated oligorhamnosides from Cleistopholis patens.
AB  - Three new (1-3) and five known (4-8) partially acetylated oligorhamnoside
      derivatives were obtained from Cleistopholis patens via high-throughput natural
      products chemistry procedures. The rapid structure elucidation and dereplication
      were performed primarily utilizing a capillary-scale NMR probe and LR-/HRESIMS
      spectroscopic methods. Compounds 1, 2, and 6 were found to possess significant in
      vitro antibacterial activity against the Gram-positive bacteria methicillin
      resistant Staphylococcus aureus ATCC 33591 and S. aureus 78-13607A with MICs of <
      or =16 microg/mL. Furthermore, 2 and 6 were found to show significant in vitro
      antibacterial activity against an expanded panel of Gram-positive pathogens
      including either ATCC strains or well-characterized clinical isolates from the
      global SENTRY Antimicrobial Surveillance Program.

PMID- 16643032
TI  - Saponins from Polygala japonica and their effects on a forced swimming test in
      mice.
AB  - Five new triterpenoid saponins, polygalasaponins E (1), F (2), G (3), H (4), and
      J (5), along with eight known ones (6-13), were isolated from the aerial parts of
      Polygala japonica. Their structures were established by chemical and
      spectroscopic means. Forced swimming tests on mice showed that saponins 1 and 4
      significantly reduce the immobility status by 58.1% and 51.3% at a dosage of 100
      mg/kg administrated orally once daily for 5 days, respectively.

PMID- 16643033
TI  - Resin glycosides from the flowers of Ipomoea murucoides.
AB  - The CHCl(3)-soluble extract from the flowers of the Mexican medicinal plant
      Ipomoea murucoides, through preparative-scale recycling HPLC, yielded murucoidins
      I-V (1-5), which are new pentasaccharides of jalapinolic acid, as well as the
      known stoloniferin I (6). Saponification of the crude resin glycoside mixture
      yielded two glycosidic acids, simonic acid B (9) and operculinic acid A (10), and
      their esterifying residues were composed of the two short-chain fatty acids, 2
      methylpropanoic and (2S)-methylbutyric acids. All the isolated compounds (1-6)
      were characterized through high-field NMR spectroscopy. Compound 4 exhibited
      marginal cytotoxicity against Hep-2 cells (ED(50) 4 microg/mL).

PMID- 16643034
TI  - Vanillic acid glycoside and quinic acid derivatives from Gardeniae Fructus.
AB  - Bioassay-directed chromatographic fractionation of an ethyl acetate extract of
      Gardenia jasminoides (Gardeniae Fructus) afforded a new vanillic acid 4-O-beta-d
      (6'-sinapoyl)glucopyranoside (1) and five new quinic acid derivatives, methyl 5-O
      caffeoyl-3-O-sinapoylquinate (2), ethyl 5-O-caffeoyl-3-O-sinapoylquinate (3),
      methyl 5-O-caffeoyl-4-O-sinapoylquinate (4), ethyl 5-O-caffeoyl-4-O
      sinapoylquinate (5), and methyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3
      methyl)glutaroylquinate (6), together with three known quinic acid derivatives,
      two flavonoids, two iridoids, and two phenolic compounds. The structures of new
      compounds were elucidated by the aid of spectroscopic methods. These compounds
      were assessed for antioxidant activity using three different cell-free bioassay
      systems and for HIV-1 integrase inhibitory activity. Five new quinic acid
      derivatives showed potent DPPH radical scavenging, superoxide anion scavenging,
      and lipid peroxidation inhibition activities. These new quinic acid derivatives
      also exhibited HIV-1 integrase inhibitory activity.

PMID- 16643035
TI  - Biotransformation of cycloartane-type triterpenes by the fungus Glomerella
      fusarioides.
AB  - Biotransformation of three cycloartane-type triterpenes, cycloartenol (1), 24
      methylenecycloartanol (2), and cycloartenone (3), by the fungus Glomerella
      fusarioides was studied. Compound 1 was converted to 3, cycloart-25-ene-3beta,24
      diol (4), and cycloartane-3beta,24,25-triol (5). Compound 2 was metabolized to
      cycloeucalenol (6) and two new compounds, 24-methylcycloartane-3beta,24,24(1)
      triol (7) and 24(1)-methoxy-24-methylcycloartane-3beta,24-diol (8). Compound 3
      was converted into two new metabolites, 4alpha,4beta,14alpha-trimethyl-9beta,19
      cyclopregnane-3,20-dione (9) and 25-hydroxy-24-methoxycycloartan-3-one (14), and
      four known compounds, viz., cycloartane-3,24-dione (10), 24-hydroxycycloart-25-en
      3-one (11), (23E)-25-hydroxycycloart-23-en-3-one (12), and 24,25
      dihydroxycycloartan-3-one (13). The structures of four new metabolites, 7, 8, 9,
      and 14, were established by spectroscopic methods.

PMID- 16643036
TI  - Caryophyllene sesquiterpenoids from a fungicolous isolate of Pestalotiopsis
      disseminata.
AB  - Three new caryophyllene-type sesquiterpene alcohols, 6-hydroxypunctaporonin E
      (1), 6-hydroxypunctaporonin B (2), and 6-hydroxypunctaporonin A (3), have been
      isolated from cultures of the fungicolous fungus Pestalotiopsis disseminata. The
      structures of 1-3 were determined mainly by analysis of 1D and 2D NMR data. The
      structure and absolute configuration of 6-hydroxypunctaporonin E (1) was
      confirmed through X-ray crystallographic analysis of its mono-bromobenzoate
      derivative. Compounds 1 and 2 showed activity against Gram-positive bacteria.

PMID- 16643037
TI  - Altenuene derivatives from an unidentified freshwater fungus in the family
      Tubeufiaceae.
AB  - Four new altenuene derivatives called dihydroaltenuenes A (1) and B (2) and
      dehydroaltenuenes A (3) and B (4), along with five known compounds, including
      isoaltenuene (5), altenuene (6), and 5'-epialtenuene (7), were isolated from
      cultures of an unidentified freshwater aquatic fungal species in the family
      Tubeufiaceae. The structures of 1-4 were determined by analysis of NMR and MS
      data. The relative stereochemistry was determined on the basis of (1)H NMR J
      values and NOE data, while the absolute configuration of a representative member
      of the group (5) was assigned by CD spectral analysis of its bis-N,N
      dimethylaminobenzoate derivative. Compounds 1, 3, 4, 5, and 6 showed antibiotic
      activity against Gram-positive bacteria.

PMID- 16643038
TI  - Hepatoprotective sesquiterpene glycosides from Sarcandra glabra.
AB  - Six new sesquiterpene glycosides, compounds 1-6, with eudesmanolide, elemanolide,
      lindenane, and germacranolide sesquiterpene aglycons, along with one known
      compound, chloranoside A (7), have been isolated from the whole plant of
      Sarcandra glabra. The structures of 1-6 were elucidated by chemical and
      spectroscopic methods including (1)H-(1)H COSY, HMQC, HMBC, and NOESY NMR
      experiments. In addition, compounds 1-7 showed pronounced hepatoprotective
      activities against D-galactosamine-induced toxicity in WB-F344 rat hepatic
      epithelial stem-like cells.

PMID- 16643039
TI  - Bioactivity profiling using HPLC/microtiter-plate analysis: application to a New
      Zealand marine alga-derived fungus, Gliocladium sp.
AB  - Using HPLC/microtiter-plate-based generation of activity profiles the extract of
      a marine alga-derived fungus, identified as Gliocladium sp., was shown to contain
      the known strongly cytotoxic metabolite 4-keto-clonostachydiol (1) and also
      clonostachydiol (2) as well as gliotide (3), a new cyclodepsipeptide containing
      several D-amino acids. The absolute configuration of 1 was elucidated by
      reduction to 2, and two further oxidized derivatives of clonostachydiol (5, 6)
      were prepared and evaluated for biological activity.

PMID- 16643040
TI  - Pregnane glycosides from Leptadenia pyrotechnica.
AB  - The whole plant of Leptadenia pyrotechnica afforded 18 new pregnane glycosides (1
      18) with sarcostin, 11-hydroxysarcostin, and deacetylmetaplexigenin as the
      aglycon moieties and acetyl, benzoyl, cinnamoyl, p-coumaroyl, and nicotinoyl
      ester moieties linked at C-12 and/or C-20 of the aglycon and hexopyranose, 6
      deoxy-3-O-methylhexopyranose, and 2,6-dideoxy-3-O-methylhexopyranose sugars
      linked at C-3 of their aglycon. The structures of these compounds were elucidated
      by spectroscopic data interpretation and from chemical evidence. The
      antiproliferative activity of all compounds was evaluated using three continuous
      murine and human culture cell lines, J774.A1, HEK-293, and WEHI-164. Compounds
      having deacethylmetaplexigenin as aglycon and a cinnamoyl ester moiety linked at
      C-12 were the most active constituents.

PMID- 16643041
TI  - Chloriolide, a 12-membered macrolide from Chloridium virescens var.
      chlamydosporum (NRRL 37636).
AB  - A new 12-membered macrolide (chloriolide; 1) was obtained from solid-substrate
      fermentation cultures of Chloridium virescens var. chlamydosporum that was
      originally isolated from decayed wood. The structure of 1 was determined by
      analysis of 1D NMR, 2D NMR, and MS data and confirmed by X-ray crystallographic
      analysis. The absolute configuration of 1 was assigned by application of the
      modified Mosher method using the (R)- and (S)-MTPA derivatives of a rearrangement
      product obtained under standard acylation conditions. The assignment made by
      analysis of the corresponding Deltadelta values was verified by X-ray
      crystallographic analysis of the (S)-MTPA derivative.

PMID- 16643042
TI  - Lophocladines, bioactive alkaloids from the red alga Lophocladia sp.
AB  - Lophocladines A (1) and B (2), two 2,7-naphthyridine alkaloids, were isolated
      from the marine red alga Lophocladiasp. collected in the Fijian Islands. Their
      structures were deduced on the basis of high-resolution mass spectra and one- and
      two-dimensional NMR spectroscopy. Lophocladine A (1) displayed affinity for NMDA
      receptors and was found to be a delta-opioid receptor antagonist, whereas
      lophocladine B (2) exhibited cytotoxicity to NCI-H460 human lung tumor and MDA-MB
      435 breast cancer cell lines. Immunofluorescence studies indicated that the
      cytotoxicity of lophocladine B (2) was correlated with microtubule inhibition.
      This is the first reported occurrence of alkaloids based on a 2,7-naphthyridine
      skeleton from red algae.

PMID- 16643043
TI  - 7alpha,20-epoxy-ent-kauranoids from Isodon parvifolius.
AB  - Nine new 7alpha,20-epoxy-ent-kaurane diterpenoids, parvifolines C-K (1-9),
      together with 12 known analogues, rabdoternin G (10), adenolin E (11), lasiodonin
      (12), lushanrubescensin F (13), parvifoliside (14), effusanin A (15), effusanin B
      (16), effusanin E (17), taibaihenryiin A (18), shikokianin (19), maoyecrystal J
      (20), and the acetonide of lasiodonin (21), were isolated from the leaves of
      Isodon parvifolius. The structures of compounds 1-9 were determined on the basis
      of spectroscopic methods including extensive 1D and 2D NMR analysis. The new
      diterpenoids (1-9) and lasiodonin (12) were evaluated for their inhibitory
      activity against A549, HT-29, and K562 cell lines.

PMID- 16643044
TI  - Nortriterpenoids from Schisandra lancifolia.
AB  - Six new nortriterpenoids, lancifodilactones I-N (1-6), as well as nine known
      ones, were isolated from the leaves and stems of Schisandra lancifolia. Their
      structures were elucidated on the basis of spectroscopic methods including 2D NMR
      analysis, and the structures of compounds 1 and 4 were further confirmed by
      single-crystal X-ray crystallography. In addition, all new compounds were tested
      for anti-HIV-1 activity.

PMID- 16643045
TI  - Antimicrobial dialkylresorcinols from Pseudomonas sp. Ki19.
AB  - Four dialkylresorcinols (1-4) were isolated from a liquid culture of Pseudomonas
      sp. Ki19. Compounds 1 and 2, 2-butyl-5-propylresorcinol and 2-hexyl-5
      methylresorcinol, respectively, have not previously been isolated from biological
      sources, whereas 3 and 4, 2-hexyl-5-propylresorcinol (DB-2073) and 2-hexyl-5
      pentylresorcinol (resorstatin), both have been found in biological systems. The
      compounds inhibited Staphyllococcus aureus at concentrations < or = 10 microg/mL
      as well as the fungi Aspergillus fumigatus and Fusarium culmorum at 50 microg/mL.
      The formation of possible antimicrobial quinone oxidation products was
      investigated under bioassay conditions, and they were not found to be responsible
      for the main antimicrobial activity.

PMID- 16643046
TI  - Bioactive exopolysaccharides from the cultured cells of tomato, Lycopersicon
      esculentum var. San Marzano.
AB  - Three exopolysaccharides, EPS(1), EPS(2), and EPS(3), were isolated from
      suspension-cultured cells of tomato (Lycopersicon esculentum, var. San Marzano).
      The partial primary structures were determined on the basis of spectroscopic
      analyses. EPS(2) was a heteropolysaccharide with a tetrasaccharide repeating unit
      constituted by sugars having one residue in alpha-manno, one residue in beta
      manno, and two different residues in beta-gluco/galacto configurations. EPS(3)
      was a heteropolysaccharide with a pentasaccharide repeating unit with sugars
      having three residues in alpha-manno, one residue in alpha-gluco/galacto, and one
      residue in beta-gluco/galacto configurations. The anticytotoxic activities of
      exopolysaccharides were tested in a brine shrimp bioassay.

PMID- 16643047
TI  - Linear sesquiterpene lactones from Anthemis auriculata and their antibacterial
      activity.
AB  - Three linear sesquiterpene lactones, anthecotulide (1), hydroxyanthecotulide (2),
      and acetoxyanthecotulide (3), were isolated from the aerial parts of Anthemis
      auriculata. Five known flavonoids, taraxa-20(30)en-3beta-ol (4), and methyl
      vanillate (5) were also isolated. The structures and the relative configuration
      of the new compounds 2 and 3 were deduced by spectroscopic methods. The in vitro
      activity of compounds 1-5 against 10 bacterial species and one fungus was tested
      using the microdilution method.

PMID- 16643048
TI  - Calocedimers A, B, C, and D from the bark of Calocedrus macrolepis var.
      formosana.
AB  - Calocedimers A, B, C, and D, together with four known compounds, platydiol, alpha
      cadinol, ferrugiol, and 6,7-dehydroferrugiol, were isolated from the bark of
      Calocedrus macrolepis var. formosana. Calocedimers A, B, C, and D are the dimers
      of abietane-O-camphane, abietane-O-cadinane, abietane-O-abietane, and abietane-O
      abietane, respectively. Their structures were elucidated from spectroscopic data.

PMID- 16643049
TI  - Granulatamides A and B, cytotoxic tryptamine derivatives from the soft coral
      Eunicella granulata.
AB  - Two new tryptamine derivatives, granulatamides A (1) and B (2), were isolated
      from the 2-propanol extract of the soft coral Eunicella granulata. Their
      structures were determined on the basis of detailed spectroscopic analysis and
      comparison with previously published data for similar compounds. Both compounds
      showed moderate in vitro cytotoxicity against a panel of 16 human tumor cell
      lines.

PMID- 16643050
TI  - Diplobifuranylones A and B, 5'-monosubstituted tetrahydro-2H-bifuranyl-5-ones
      produced by Diplodia corticola, a fungus pathogen of cork oak.
AB  - Two new 5'-monosubstituted tetrahydro-2H-bifuranyl-5-ones, named
      diplobifuranylones A and B (1 and 2), were isolated from the culture filtrates of
      Diplodia corticola, the causal agent of a canker of cork oak (Quercus suber). The
      same fungus also produced eight known metabolites, namely, the diplopyrone,
      (3S,4R)-trans- and (3R,4R)-cis-4-hydroxymellein, sapinofuranone B and its (S,S)
      enantiomer, and sphaeropsidins A-C. Diplobifuranylones A and B (1 and 2) were
      characterized, using spectroscopic and chemical methods, as two diastereomeric 5'
      (1-hydroxyethyl)-3,4,2',5'-tetrahydro-2H-[2,2']bifuranyl-5-ones. While the
      relative stereochemistry of the two metabolites (1 and 2) was deduced by NOESY
      and ROESY experiments, the absolute stereochemistry of the chiral carbon of the
      hydroxyethyl side chain at C-5', determined by application of Mosher's method,
      proved to be S and R in 1 and 2, respectively. Assayed on a nonhost plant,
      diplobifuranylones A and B did not show phytotoxic activity. In an Artemia salina
      larvae lethality bioassay neither 1 nor 2 was toxic at the highest concentration
      tested (300 microg/mL).

PMID- 16643051
TI  - Xenicane-type diterpenes with cytotoxicity from Xenia florida.
AB  - Chromatographic investigation of an acetone extract of the octocoral Xenia
      florida afforded three new xenicane diterpenes, namely, florxenilide A (1),
      florxenilide B (2), and florxenilide C (3), in addition to seven known xenicane
      diterpenes and two known cadinene sesquiterpenes. Structures were elucidated
      through spectroscopic analysis, especially 2D NMR, and chemical derivatization.
      The absolute configuration of 1 was determined by NOESY, CD, and Mosher's
      methods. Florxenilides A (1) and B (2) exhibited cytotoxicity against human colon
      cancer (WiDr) cells at 4.5 and 3.7 muM, respectively.

PMID- 16643052
TI  - Neuroprotective bibenzyl glycosides of Stemona tuberosa roots.
AB  - Three new bibenzyl glycosides characterized as stilbostemin B 3'-beta-D
      glucopyranoside (1), stilbostemin H 3'-beta-D-glucopyranoside (2), and
      stilbostemin I 2"-beta-D-glucopyranoside (3) were isolated from the roots of
      Stemona tuberosa. All three bibenzyl glycosides significantly protected human
      neuroblastoma SH-SY5Y cells from 6-hydroxydopamine-induced neurotoxicity.

PMID- 16643053
TI  - Lignan oligosaccharide esters from Eritrichium rupestre.
AB  - Three new lignan oligosaccharide esters, rupestrin A (1), rupestrin B (2), and
      rupestrin C (3), were isolated from the ethanol extract of Eritrichium rupestre.
      Their structures were elucidated on the basis of spectroscopic and chemical
      evidence.

PMID- 16643054
TI  - Cytotoxic dihydroagarofuranoid sesquiterpenes from the stem of Microtropis
      fokienensis.
AB  - Four dihydroagarofuran sesquiterpene polyesters (1-4) have been isolated from the
      stem of Microtropis fokienensis. The structures of these new compounds were
      determined through spectroscopic analyses. Compound 1, 2, 3, and 4 exhibited
      cytotoxicities (IC(50) values < 0.1 microg/mL) against P-388 and HT-29 cell lines
      in vitro.

PMID- 16643055
TI  - Neuroprotective diterpenes from the fruiting body of Antrodia camphorata.
AB  - Three new compounds, 19-hydroxylabda-8(17)-en-16,15-olide (1), 3beta,19
      dihydroxylabda-8(17),11E-dien-16,15-olide (2), and 13-epi-3beta,19-dihydroxylabda
      8(17),11E-dien-16,15-olide (3), together with four known compounds, 19
      hydroxylabda-8(17),13-dien-16,15-olide (4), 14-deoxy-11,12
      didehydroandrographolide (5), 14-deoxyandrographolide, and pinusolidic acid, were
      isolated from the fruiting bodies of Antrodia camphorata. The structures of
      compounds 1-3 were elucidated by the analysis of their spectroscopic data. The in
      vitro neuroprotective activity of all compounds was evaluated, and compounds 1-5
      protected neurons from Abeta damage by 39.2, 35.0, 36.7, 30.6, and 27.0%,
      respectively, at concentrations between 5 and 20 microM.

PMID- 16643056
TI  - Aromatic constituents of Uvaria grandiflora.
AB  - Grandiuvarone A (1) and grandiuvarins A-C (2-4) were isolated from the bark of
      Uvaria grandiflora. The structures of these new aromatic compounds were
      elucidated on the basis of spectroscopic analyses, especially 2D NMR techniques.
      Only compound 1 exhibited antileishmanial activity, with IC(50)/IC(90) values of
      0.7/1.5 microg/mL. The positive controls pentamidine and amphotericin B had
      IC(50)/IC(90) values of 1.6/6.6 and 0.17/0.34 microg/mL, respectively.

PMID- 16643057
TI  - Bisabolane sesquiterpenes from the roots of Ligularia cymbulifera.
AB  - Eight new highly oxygenated bisabolane sesquiterpenes (1-8), of which one
      contains a chlorine atom, were obtained in a phytochemical investigation of the
      roots of Ligularia cymbulifera, and their structures were elucidated by
      interpretation of spectroscopic data. Their relative configurations were
      clarified by a detailed analysis of (1)H NMR coupling constants and by NOE
      experiments. Compounds 1-8 were evaluated for antimicrobial activity against
      three bacterial cultures and a yeast culture.

PMID- 16643058
TI  - Interference by naturally occurring fatty acids in a noncellular enzyme-based
      aromatase bioassay.
AB  - Natural product drug discovery efforts frequently utilize noncellular screening
      assays. Fatty acids are commonly found in natural product extracts, and some have
      been shown to interfere with noncellular assays. Several pure fatty acids were
      tested using a noncellular aromatase assay, with the unsaturated analogues
      showing strong inhibitory activity, while the saturated analogues were inactive.
      Unsaturated fatty acids were further tested against SK-BR-3 hormone-independent
      human breast cancer cells that overexpress aromatase and were found to be
      inactive. In natural product screening efforts, especially using plant seeds, it
      is recommended that extracts active in noncellular bioassays should be
      dereplicated for the presence of fatty acids prior to bioassay-guided
      fractionation.

PMID- 16643059
TI  - 5-alkylresorcinols from Merulius incarnatus.
AB  - Two new, 5-heptadeca-8'Z,11'Z,16-trienylresorcinol (1) and 5-heptadeca
      9'E,11'Z,16-trienylresorcinol (2), and six known 5-alkylresorcinols (3-8) were
      isolated from the mushroom Merulius incarnatus. Compound 2 is the first 5
      alkylresorcinol derivative that contains a trans-cis conjugated double bond
      system. Compounds 1, 2, 5, 6, 7, and 8 were found to inhibit methacillin
      resistant Staphylococcus aureus (MRSA) with IC(50) values of 2.5, 15, 9.5, 8.0,
      5.0, and 6.5 microg/mL, respectively. Compound 1 was also active against
      leishmania, with an IC(50) value of 3.6 microg/mL, and showed no cytotoxicity in
      our Vero cell test up to a concentration of 25 microg/mL. The structures of these
      isolates were determined by spectroscopic data including 1D and 2D NMR.

PMID- 16643060
TI  - Sundaicumones A and B, polyprenylated acylphloroglucinol derivatives from
      Calophyllumsundaicum with weak activity against the glucocorticoid receptor.
AB  - Bioassay-directed fractionation using a glucocorticoid receptor assay led to the
      isolation of two new, weakly active polyprenylated acylphloroglucinol
      derivatives, sundaicumones A (1) and B (2), from the leaves of Calophyllum
      sundaicum collected in Singapore. The structures of 1 and 2, which were
      established by spectroscopic methods, contain a 3-substituted hexanoic acid unit
      not previously reported in other polyprenylated acylphloroglucinols.

PMID- 16643061
TI  - Highly substituted terphenyls as inhibitors of parasite cGMP-dependent protein
      kinase activity.
AB  - Parasite cGMP-dependent protein kinase (PKG) is one of the validated biochemical
      targets for the treatment of coccidiosis. We screened our library of natural
      product extracts for inhibitors of parasite PKG for the discovery of
      anticoccidial leads. Terferol (1) and three new terphenyls (2, 3, and 4) were
      isolated using bioassay-guided fractionation of the microbial extract of a Phoma
      sp. by a high-throughput two-step isolation method employing LH-20 and reversed
      phase HPLC. These compounds inhibited parasite PKG with IC(50) values in the
      range 0.9-5.8 microM.

PMID- 16643062
TI  - An antimalarial tetrapeptide from the entomopathogenic fungus Hirsutella sp. BCC
      1528.
AB  - Hirsutellic acid A (1), a new linear tetrapeptide possessing an anthranilic acid
      residue at the C-terminus, was isolated from a fermentation broth of the
      entomopathogenic fungus Hirsutella sp. BCC 1528. The structure of this compound
      was elucidated by NMR and MS analyses, and its absolute configuration was deduced
      by HPLC analysis of the acid hydrolysate using a chiral column. Hirsutellic acid
      A exhibits activity against the malarial parasite Plasmodium falciparum K1 with
      an IC(50) value of 8.0 microM, while it was noncytotoxic to Vero cells at a
      concentration of 95 microM.

PMID- 16643063
TI  - Isolation of gelsedine-type indole alkaloids from Gelsemium elegans and
      evaluation of the cytotoxic activity of gelsemium alkaloids for A431 epidermoid
      carcinoma cells.
AB  - Four new gelsedine-type indole alkaloids (1-4) were isolated from the leaves of
      Gelsemium elegans, together with 11 known alkaloids. The structures were
      determined as 14-acetoxygelsenicine (1), 14-acetoxy-15-hydroxygelsenicine (2), 14
      hydroxy-19-oxogelsenicine (3), and 14-acetoxygelselegine (4), respectively, by
      spectroscopic analysis. The cytotoxic effects of 14 Gelsemium alkaloids including
      two new compounds (1, 2) were evaluated using the A431 human epidermoid carcinoma
      cell line. Of these, the gelsedine-type alkaloids 14-acetoxy15-hydroxygelsenicine
      (2) [corrected] 14,15-dihydroxygelsenicine (5), gelsedine (7), and gelsemicine
      (8) showed potent cytotoxic effects.

PMID- 16643064
TI  - Prenylated flavonoids from the heartwood of Artocarpus communis with inhibitory
      activity on lipopolysaccharide-induced nitric oxide production.
AB  - A new prenylated chalcone, 3' ',3' '-dimethylpyrano[3',4']2,4,2'
      trihydroxychalcone (1), was isolated from the heartwood of Artocarpus communis.
      Two flavonoid derivatives, (-)-cycloartocarpin (9) and (-)-cudraflavone A (10),
      were isolated as new isomers. In addition, eight known flavonoids,
      isobacachalcone (2), morachalcone A (3), gemichalcones B (4) and C (5),
      artocarpin (6), cudraflavone C (7), licoflavone C (8), and (2S)-euchrenone a(7)
      (11), were isolated and identified from this plant for the first time. Compounds
      1-4, 6, and 11 exhibited potent inhibitory activity on nitric oxide production in
      RAW264.7 LPS-activated mouse macrophage cells with IC(50) values of 18.8, 6.4,
      16.4, 9.3, 18.7, and 12.3 microM, respectively. The structure of compound 1 was
      elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments.

PMID- 16643065
TI  - Botcinins E and F and Botcinolide from Botrytis cinerea and structural revision
      of botcinolides.
AB  - Botcinins E and F were isolated together with the known botcinolide. The
      structures of botcinins E and F were determined to be 3-O-deacetylbotcinin A (5)
      and 3-O-deacetyl-2-epi-botcinin A (6), respectively, by spectroscopic methods and
      chemical conversion. The structure of botcinolide was revised on the basis of
      spectroscopic data and chemical conversion. Botcinolide was originally reported
      as a nine-membered lactone (7), but the revised structure is the seco acid of
      botcinin E (13). Thus botcinolide is renamed botcinic acid, and homobotcinolide
      is renamed botcineric acid. Reinvestigation of the spectroscopic data reported
      for all botcinolide analogues indicates that 4-O-methylbotcinolide and 3-O-acetyl
      2-epibotcinolide are the same as a methyl ester of botcinic acid (13a) and
      botcinin A (1), respectively, and that 2-epibotcinolide may be the same as
      botcinin E (5). Compounds 5, 6, and 13 showed weak antifungal activity against
      Magnaporthe grisea, a pathogen of rice blast disease.

PMID- 16643066
TI  - Midterm results of aortic diameter outcomes after thoracic stent-graft
      implantation for aortic dissection: a multicenter study.
AB  - PURPOSE: To evaluate aortic diameter outcomes after stent-graft implantation for
      aortic dissection in the descending thoracic aorta. METHODS: Fifty patients with
      type A dissection after ascending aortic surgery (n = 10), type B dissection (n =
      34), or intramural hematoma (n = 6) underwent stent-graft repair in 3 centers.
      Thrombosis and aortic diameter were analyzed by computed tomographic angiography
      at different levels of the aorta before stent-graft implantation, at discharge,
      and at follow-up. Measurements were standardized. RESULTS: In all, 67 stent
      grafts were implanted for acute (n = 18) and chronic (n = 32) dissection. Stent
      graft placement was successfully performed with high technical success (100%)
      despite 4 major complications (iliac thrombosis in 2 cases, aortic rupture, and a
      type A dissection) in 3 (6%) patients. Complete thrombosis of the thoracic false
      lumen was observed in 42% and 63% of cases at discharge and at follow-up (mean 15
      months), respectively. At follow-up, the diameters of the entire aorta (mean 5
      mm, p < 0.05) and the false lumen (mean 11 mm, p < 0.0001) decreased. Diameters
      of the abdominal aorta remained stable in association with persistent false lumen
      perfusion at this level. Aortic diameter results were better in the subgroup of
      patients with intramural hematoma compared to patients with Marfan syndrome.
      Three early deaths unrelated to the stent-graft procedure occurred; 2 patients
      with partial thrombosis of the false lumen died in follow-up secondary to aortic
      diameter growth. CONCLUSION: Complete thrombosis of the false lumen by stent
      graft coverage of the entry tear results in decreased diameter of the entire
      aorta. In patients with partial thrombosis of the false lumen, the aneurysm
      continues to enlarge.

PMID- 16643067
TI  - Pilot study of dynamic cine CT angiography for the evaluation of abdominal aortic
      aneurysms: implications for endograft treatment.
AB  - PURPOSE: To utilize 40-slice electrocardiographically (ECG)-gated cine computed
      tomographic angiography (CTA) to characterize normal aortic motion during the
      cardiac cycle at relevant anatomical landmarks in preoperative abdominal aortic
      aneurysm (AAA) patients. METHODS: In 10 consecutive preoperative AAA patients (10
      men; mean age 78.8 years, range 69-86), an ECG-gated CTA dataset was acquired on
      a 40-slice CT scanner using a standard radiation dose. CTA quality was graded and
      scan time was measured. Pulsatility measurements at multiple relevant anatomical
      levels were performed in the axial plane. Changes in aortic circumference were
      determined for both the aortic wall and the luminal diameter. RESULTS: All 10 CT
      scans were of good quality. All patients could be scanned in 14 to 33 seconds
      (mean 21). At each anatomical level measured, there was a 2.2- to 3.4-mm increase
      in the aortic wall circumference per cardiac cycle. A similar increase was
      observed in luminal circumference, with a 2.4- to 3.6-mm increase per cycle.
      CONCLUSION: This study introduces the concept of dynamic cine CTA imaging of
      aortic motion, providing insight into the pathophysiology of abdominal aortic and
      iliac pulsations. Patients with AAAs selected for EVAR demonstrate changes in
      aortic circumference with each cardiac cycle that may have consequences for
      endograft sizing and future design. The potential for graft migration,
      intermittent type I endoleak, and poor patient outcome following EVAR can be
      anticipated. Complex aortic dynamics deserve increased scrutiny in an effort to
      prevent potential complications.

PMID- 16643068
TI  - Aneurysm sac pressure monitoring: effect of pulsatile motion of the pressure
      sensor on the interpretation of measurements.
AB  - PURPOSE: To determine the effect of pulsatile motion of graft-attached pressure
      sensors on the accuracy of aneurysm sac pressure measurement. METHODS: Pressure
      inside a pressure box was measured with a sensor attached to a stent-graft
      (Sensorgraft) facing a sensor in fixed position (Sensorbox). Maximum inter-sensor
      variation of Sensorgraft and Sensorbox was determined in static experiments.
      Experiments with pulsatile circulation were performed with a compliant and a
      noncompliant stent-graft at 120/80 mmHg and 160/95 mmHg. Pressure measurements in
      the box were repeated after the box pressure was increased from 0 to 120 mmHg.
      Sensorgraft motion was measured by ultrasound. Measurements with Sensorgraft were
      compared to those with Sensorbox using Pearson correlation coefficients to
      determine the concordance between the sensors. RESULTS: The maximum inter-sensor
      variation was 4 mmHg. Increased box pressure induced progressive pulsatile graft
      and sensor motion during all experiments. During the experiments with the
      compliant graft at systemic pressures of 120/80 and 160/95 mmHg, the maximum
      inter-sensor variation was exceeded at box pressures of 65 and 75 mmHg,
      respectively. The sensor motion at these box pressures was 214+/-2.70 microm and
      210+/-0.93 microm, respectively. Measurements of Sensorgraft were higher than
      Sensorbox, up to 13 mmHg at a box pressure of 120 mmHg. The Pearson correlation
      coefficients during these experiments were 0.99 and 1.00 (p < 0.001),
      respectively. In the experiments with the noncompliant graft, the maximum inter
      sensor variation was not exceeded, and sensor motion was only 7 +/- 0.46 microm
      and 26 +/- 1.48 microm, respectively. The Pearson correlation coefficient during
      these experiments was 1.00 (p < 0.001). CONCLUSION: Pulsatile sensor motion can
      influence the accuracy of pressure measurement. More compliant grafts are more
      susceptible to this phenomenon. Despite false high pressure measurements, stent
      graft-attached pressure sensors seem appropriate to follow pressure trends in the
      aneurysm sac.

PMID- 16643069
TI  - Fascia suturing of large access sites after endovascular treatment of aortic
      aneurysms and dissections.
AB  - PURPOSE: To evaluate a technique for closure of a femoral artery access in which
      the cribriform fascia covering the common femoral artery is sutured. METHODS: A
      consecutive series of 127 patients (103 men; median age 74 years, range 45- 89)
      underwent endovascular aortic aneurysm repair between August 2001 and September
      2004. Twelve patients underwent a secondary intervention for a total of 139
      procedures in the group. Sixty-one (43.9%) of the 139 operations were acute.
      Among the 257 femoral arteries used for access, a fascia suturing technique was
      performed in 131 (51.0%). Data were collected for analysis of access site
      complications, bleeding, thrombosis, pseudoaneurysm, and stenosis. A subgroup of
      72 patients had ankle-brachial indexes (ABI) recorded; another subgroup of 50
      patients were also investigated by duplex ultrasonography. RESULTS: Complications
      occurred in 18 (13.7%) of the 131 sutured cases. The majority (n = 16) arose
      within 24 hours: 8 cases of perioperative bleeding or thrombosis required open
      surgery and 8 cases were reoperated within 24 hours for bleeding (n = 4),
      thrombosis (n = 3), and 1 intimal dissection. The acute failure rate was 12.2%.
      Two patients had late complications: 1 case of neuralgia and 1 pseudoaneurysm
      that required acute surgery 28 months postoperatively. The ABI did not change
      significantly from pre- to postoperatively in the 72 patients examined. Five
      patients with stenoses did not have a reduction in ABI. In the 66 sites examined
      with ultrasound in 50 patients, 3 minor pseudoaneurysms were detected.
      CONCLUSION: The fascia suturing technique for closure of a femoral artery access
      during endovascular repair of aortic diseases is feasible, even in acute
      situations. Failures can be managed easily. Late complications requiring
      additional procedures are rare.

PMID- 16643070
TI  - Biological coating for arterial stents: the next evolutionary change in stents.
AB  - PURPOSE: To describe the in vivo results of a promising new stent-graft lined
      with peritoneum. METHODS: Eighteen dogs underwent balloon angioplasty injury to
      the bilateral iliac arteries followed by placement of either an 8-mm x 5-cm
      glutaraldehyde-fixed bovine peritoneum- lined balloon-expandable stent (PLS) or a
      similarly sized, commercially prepared, polyester-lined self-expanding stent
      (DLS) as a control. Animals were sacrificed at 1 and 6 months. Biplanar
      arteriography and intravascular ultrasound were done at the time of sacrifice,
      and the vessels were harvested after perfusion fixation for
      histology/morphometry. Immunofluorescence with CD34 and factor VIII staining was
      used to evaluate endothelialization, while alpha-actin was used to quantify
      smooth muscle cell (SMC) deposition. RESULTS: At 1 month, all vessels were patent
      in both groups. At 6 months, 8 of 9 vessels were open in the PLS group versus 6
      of 9 in the control DLS group. Vessel lumen diameter at 1 month was significantly
      greater in the PLS vessels compared to the DLS group at 1 cm above the stent
      (35.9 +/- 4.4 versus 29.4 +/- 4.7 mm2; p = 0.02) and 1 cm below the stent (37.2
      +/- 7.1 versus 25.2 +/- 3.2 mm2; p = 0.005); these results persisted to 6 months.
      Histological morphometry demonstrated progression of neointimal hyperplasia in
      the DLS stent between 30 and 180 days (8.3 +/- 1.79 versus 14.9 +/- 6.6 mm2; p =
      0.03), whereas the peritoneum-lined stent had no change during the same time
      period (4.62 +/- 0.98 versus 4.72 +/- 0.97 mm2; p = 0.85). The same patterns were
      true for the intima:media ratio. Immunohistochemistry demonstrated complete
      endothelialization at 6 months in both DLS and PLS. However, SMC staining with
      alpha-actin demonstrated more smooth muscle actin-positive cells in the DLS
      compared to the PLS (327 +/- 87 versus 262 +/- 73 counts/5 high-powered fields; p
      = 0.04). CONCLUSION: Peritoneum-lined stents offer a novel method to improve
      patency of lower extremity arterial stents.

PMID- 16643071
TI  - Combined sustained delivery of basic fibroblast growth factor and administration
      of granulocyte colony-stimulating factor: synergistic effect on angiogenesis in
      mouse ischemic limbs.
AB  - PURPOSE: To investigate whether the efficacy of a single angiogenic therapy
      (sustained delivery of basic fibroblast growth factor [bFGF] or administration of
      granulocyte colony-stimulating factor [G-CSF]) can be enhanced further by
      combining the therapies. METHODS: One day after surgical induction of hind-limb
      ischemia, groups of 6 mice were randomized to receive either no treatment,
      sustained delivery (SD) of bFGF, endothelial progenitor cell (EPC) mobilization
      with G-CSF administration, or a combination of bFGF SD + G-CSF administration.
      RESULTS: G-CSF administration increased significantly (p < 0.05) the number of
      EPC lineages (CD34 + /AC133 + cells) in both peripheral blood and bone marrow
      compared to no G-CSF administration. The bFGF SD and G-CSF administration
      individually increased the capillary and arteriole densities significantly versus
      no treatment (capillary density: 659 +/- 48/mm2 and 385 +/- 59/mm2, respectively,
      versus 280 +/- 28/mm2; p < 0.05; arteriole density: 34 +/- 9/mm2 and 41 +/-
      6/mm2, respectively, versus 15 +/- 2/mm2; p<0.05). Importantly, bFGF SD + G-CSF
      further increased the capillary and arteriole densities compared to either
      strategy alone (capillary density: 786 +/- 40/mm2 versus 659 +/- 48/mm2 and 385
      +/- 59/mm2, respectively, p < 0.05; arteriole density: 55 +/- 10/mm2 versus 34 +/
      9/mm2 and 41 +/- 6/mm2, respectively, p < 0.05). CONCLUSION: This study
      demonstrates that the combined therapy of sustained bFGF delivery and G-CSF
      administration potentiates the angiogenic efficacy of either single therapy in
      mouse hind-limb ischemia models.

PMID- 16643072
TI  - Grading of internal carotid artery stenosis: comparative analysis of different
      flow velocity criteria and multidetector computed tomographic angiography.
AB  - PURPOSE: To evaluate multidetector computed tomographic angiography (CTA) versus
      published color Doppler sonography (CDS) velocity criteria in the grading of
      internal carotid artery (ICA) stenosis. METHODS: Sixty-eight consecutive patients
      (50 men; mean age 70.2 +/- 8.1 years, range 51- 85) with known ICA stenosis and
      complete CTA and CDS data for 127 carotid arteries were enrolled in this
      retrospective analysis. The degree of stenosis was determined using CDS
      velocities according to 5 published sets of criteria, as well as the criteria
      used at the authors' institution. These outcomes were then correlated using kappa
      statistics with the results of multidetector CTA according to NASCET. RESULTS:
      The best overall agreement was achieved applying the criteria sets of Hwang
      (kappa = 0.70) and AbuRahma (kappa = 0.68). All 5 occlusions were correctly
      identified with both modalities. CTA detected 73 ICA stenoses > 70%; the best
      correlation was with the application of Hwang criteria, which correctly
      identified 69 (94.5%) > 70% stenoses. In order of increasing tendency to
      underscore the grade of stenosis, the corresponding results for the other
      criteria sets were 62 (84.9%) for Mittl, 59 (80.8%) for AbuRahma, 55 (75.3%) each
      for Nicolaides and Filis, and 50 (68.5%) for Nederkoorn. CTA detected 85 stenoses
      >50%; the sensitivity of all applied CDS criteria sets exceeded 90%. CONCLUSION:
      Grading of ICA stenosis > 70% with CDS and CTA results in clinically relevant
      discrepancies, with higher grades of stenoses assessed by CTA. The choice of CDS
      grading criteria is of significant clinical importance, especially in the
      identification of high-grade ICA stenosis.

PMID- 16643073
TI  - Endovascular treatment of soft carotid plaques: a single-center carotid stent
      experience.
AB  - PURPOSE: To report a prospective evaluation of the 30-day clinical neurological
      outcome in patients percutaneously treated for severe symptomatic and
      asymptomatic soft echolucent carotid plaques under cerebral protection from a
      proximal flow blockade system. METHODS: From December 2001 to February 2005, 84
      consecutive patients (63 men; mean age 70.7 +/- 7.1 years, range 58-81) with
      documented soft echolucent (gray scale median < 25) extracranial carotid lesions
      were enrolled in a study of percutaneous stenting under cerebral protection
      achieved by a proximal endovascular clamping device. Primary endpoint of the
      study was the all stroke and death rate at 30 days. Secondary endpoints were
      angiographic success and any complication between discharge and 30 days. All
      adverse events were analyzed by an independent neurological team. RESULTS: Total
      neurological events at 30-day follow-up included 3 transient ischemic attacks and
      1 minor stroke (4.8% neurological event rate). The 30-day rates of stroke and
      neurological death/stroke were both 1.2%; the all death/stroke rate was 2.4%.
      Clamping intolerance was observed in 5.9% of cases, but there was no interruption
      in the procedure or clinical sequelae. In 66.7% of patients, visible debris was
      collected during the procedure. CONCLUSION: Protected CAS with proximal flow
      blockage can successfully be applied in selected patients for soft carotid
      plaques at high risk for intraprocedural embolic events.

PMID- 16643074
TI  - Filter-protected carotid stenting via a minimal cervical access with transitory
      aspirated reversed flow during initial passage of the target lesion.
AB  - PURPOSE: To evaluate the preliminary results of filter-protected carotid artery
      stenting (CAS) via a minimal cervical access, with temporary common carotid
      artery (CCA) occlusion and aspiration in selected high-risk candidates for
      carotid endarterectomy. METHODS: Since February 2002, 26 patients (17 men; mean
      age 73.7 years, range 54-98) at high surgical risk according to the SAPPHIRE
      eligibility criteria underwent 29 transcervical CAS procedures under filter
      protection. Under general anesthesia, a 6-F short introducer sheath was directly
      mounted in the CCA through a small (2-4 cm) laterocervical cutdown. The CCA was
      briefly clamped, and blood was aspirated while the filter device was positioned
      above the target lesion. With the filter in place and the clamp released, nitinol
      stents were deployed under filter protection. Hemostasis was achieved by direct
      suture. RESULTS: Twenty-eight (96%) interventions were technically successful; 1
      complex lesion could not be crossed and was converted to surgery. Mean clamping
      time was 1.7 (range 1.0-3.5) minutes. Combined 30-day stroke/mortality was 0%.
      Ultrasound surveillance demonstrated a < 60% asymptomatic in-stent restenosis in
      1 (4%) patient with radiation-induced arteritis after 28 months. During a mean
      follow-up of 11.6 months (range 3-38), 1 (4%) minor ipsilateral stroke was noted
      at 6 months in a patient whose antiplatelet therapy was transitorily interrupted.
      CONCLUSION: Our preliminary observations from this small early experience suggest
      that this variant CAS technique is feasible and probably diminishes the
      neuroembolic risk during initial navigation of the ICA target stenosis.

PMID- 16643075
TI  - Assessment of flow changes in the circle of Willis after stenting for severe
      internal carotid artery stenosis.
AB  - PURPOSE: To assess flow velocities in the cerebral arteries after carotid artery
      stenting (CAS) in patients with unilateral versus bilateral lesions and analyze
      velocities in patients with neurological complications after CAS. METHODS: Ninety
      two patients (68 men; mean age 63.2 +/- 8.4 years, range 44-82) with internal
      carotid artery (ICA) stenoses were divided according to unilateral (group I, n =
      72) or bilateral (group II, n = 20) disease. Fifty age- and gender-matched
      patients without lesions in the extra- or intracranial arteries served as a
      control group. Transcranial color-coded Doppler ultrasound was performed prior to
      and within 24 hours after CAS in the test groups; systolic velocities were
      assessed ipsilateral (i) and contralateral (c) to the CAS site in the middle
      cerebral artery (MCA) and anterior cerebral artery (ACA). RESULTS: Collateral
      flow via the anterior communicating artery (ACoA) was found in all group-II
      patients and 90% of group-I patients. After CAS, collateral flow through the ACoA
      ceased, and the velocity increased by 26% in the iMCA in group I compared to
      controls (p < 0.001). In group II, iMCA flow increased by 30% (p < 0.001) and
      flow via the ACoA (p < 0.001) increased, resulting in normalization of cMCA
      velocities (p = 0.928). In 89 (96.7%) subjects, CAS was uncomplicated.
      Hyperperfusion syndrome occurred in 2 (2.2%) patients, both with bilateral ICA
      stenoses; 1 (1.1%) transient ischemic attack was seen in a patient with
      unilateral disease. In the patients with hyperperfusion syndrome, the MCA
      velocities were 2.7- and 7.4-fold higher, respectively, versus before CAS and 2
      fold higher than in controls. CONCLUSION: Uncomplicated CAS results in an iMCA
      velocity increase >25% compared to controls. MCA velocities in hyperperfusion
      syndrome were greatly increased versus before CAS and in controls.

PMID- 16643076
TI  - Rationale and design of a multidisciplinary national real-world registry on
      carotid stenting: the Italian Registry for Carotid Stenting (RISC).
AB  - The Registro Italiano per lo Stenting Carotideo (RISC, Italian Registry for
      Carotid Stenting) has been organized by Italian specialists from different
      disciplines directly involved in the prevention of stroke due to carotid plaques
      through stenting of carotid lesions. The Registry has been endorsed by the
      national societies of 4 different specialties: vascular surgery, interventional
      cardiology, radiology, and neuroradiology. Each society contributed in the
      planning stage. The basis for the registry is to collect data on carotid stenting
      procedures performed by different specialists with different techniques in a
      "real-world" setting without the limitations of a randomized clinical trial. The
      Registry was funded to enroll at least 1200 patients over a minimum period of 36
      months. The results will be analyzed using the intention-to-treat principle and
      are anticipated in late 2006. Primary endpoints of the registry are the 30-day
      combined death and stroke rate and the occurrence of restenosis and ipsilateral
      neurological deficit at 12 and 24 months. Considerable attention has been paid to
      the registry's quality control program to ensure scientific validation. An online
      database facilitates the collection of data with speed and accuracy.

PMID- 16643077
TI  - Outcome after endovascular treatment of deep femoral artery stenosis: results in
      a consecutive patient series and systematic review of the literature.
AB  - PURPOSE: To evaluate immediate and midterm clinical outcomes after percutaneous
      transluminal angioplasty (PTA) of deep femoral artery stenosis in patients with
      chronically occluded superficial femoral arteries (SFA) and to report the results
      of a systematic review of the literature in this field. METHODS: A retrospective
      analysis was conducted of 55 consecutive patients (42 men; median age 72 years,
      interquartile range [IQR] 63-79) with severe intermittent claudication (n = 38)
      or critical limb ischemia (n = 17) who underwent balloon angioplasty of deep
      femoral artery stenosis. Patients were followed with ankle-brachial index (ABI)
      measurement, estimation of maximum walking capacity, clinical staging of
      peripheral artery disease (PAD), and duplex ultrasound imaging for restenosis. A
      systematic review of the literature using MEDLINE, EMBASE, and a hand search was
      done. RESULTS: Technical success (residual stenosis < 30%) was achieved in 85%
      (47/55), with 1 (2%) minor complication. The median ABI marginally increased from
      0.48 at baseline to 0.53 post intervention without significant difference in the
      change of ABI between patients with supra- or infragenicular reconstitution of
      the femoropopliteal runoff. During a median 13-month (IQR 3-42) follow-up, no
      significant improvement in ABI or walking distance was maintained, and only 16
      (29%) patients reported a sustained clinical improvement by 1 PAD stage.
      Cumulative patency and reintervention-free survival rates were, respectively, 71%
      and 61% at 1 year and 49% and 48% at 3 years. In the literature, only case series
      were found, but no randomized trial evaluating the efficacy of deep femoral
      artery PTA. CONCLUSION: PTA of the deep femoral artery can be performed with high
      technical success rates at a low interventional risk. However, in the majority of
      patients, this technique yields no sustained hemodynamic or clinical benefit. Due
      to a high rate of late failures, it should be reserved for limb salvage in
      patients without a surgical alternative.

PMID- 16643078
TI  - Long-term results after primary stenting of distal aortic stenosis.
AB  - PURPOSE: To review the long-term results of primary stent placement in the distal
      aorta above the bifurcation. METHODS: Fourteen patients (8 men; mean age 62
      years, range 46-82) underwent primary stent implantation performed by an
      interdisciplinary radiosurgical team. In 10 patients, a long-term follow-up
      examination consisting of patient history, clinical examination, and duplex
      sonography was performed. The ankle-brachial index (ABI) for the posterior tibial
      artery was calculated on the basis of Doppler pressure measurements. RESULTS: The
      clinical success rate at the first follow-up examination (mean 2.9 months, range
      2.1-4.4) was 100% (n = 14). The mean baseline ABI of 0.64 +/- 0.12 had risen to
      1.02 +/- 0.10 (p < 0.0001). At midterm follow-up (mean 22.8 months, range 14-42)
      in 12 patients, the ABI was 0.96 +/- 0.12 (p < 0.0001 versus baseline). At a mean
      86 months (range 51-119) after stent treatment, the ABI in 10 patients was 0.90
      +/- 0.20 (p < 0.0001 versus baseline). Over the long term, the clinical success
      rate was 70%. Deterioration was due to the progression of atherosclerosis distal
      to the aorta; duplex sonography showed no aortic restenosis or occlusion.
      CONCLUSION: In view of the excellent long-term results in our small series,
      primary stent placement in focal abdominal aortic stenosis in properly selected
      patients is a durable treatment. In addition, the mortality and morbidity risks
      are markedly reduced compared with open surgery.

PMID- 16643079
TI  - Assessment of a virtual interventional simulator trainer.
AB  - PURPOSE: To assess the construct validity of the Procedicus Virtual
      Interventional Simulator Trainer (Procedicus-VIST) and its use as a training
      tool. METHODS: Two groups comprised of 8 interventional radiologists (experts)
      and 8 medical students (novices) performed 6 renal artery procedures on the
      Procedicus-VIST. All participants received a 45-minute standardized didactic
      introduction before starting the simulations. The first 2-hour session was used
      for familiarization, whereas the second session constituted the testing period.
      During each procedure, objective performance data including procedure time,
      fluoroscopic time, contrast, cine loops, lesion coverage, tool:lesion ratio,
      placement accuracy, and residual stenosis were recorded by the Procedicus-VIST
      software. Exit surveys were completed to document demographic and subjective
      data. A visual analogue scale (VAS) from 0 to 100 was used to rate total,
      guidewire, catheter, balloon, stent, fluoroscopic, and joystick realism, as well
      as the simulator's pedagogic value. RESULTS: There were no significant
      differences in performances between the 2 groups in residual stenosis, placement
      accuracy, procedure time, number of cine loops, lesion coverage, or tool:lesion
      ratio. The total fluoroscopic use was greater for the novice group (p < 0.01).
      Experts rated 6 of the 8 subjective parameters favorably, whereas the novice
      group approved of 7. CONCLUSIONS: Using this study design, the quantitative
      metrics recorded by the Procedicus-VIST software failed to stratify performances
      based upon experience level, with the exception of fluoroscopic use.
      Investigation comparing standard training to virtual reality training should be
      performed to assess any differences in actual performance in the catheterization
      laboratory.

PMID- 16643080
TI  - Endovenous ablation of incompetent saphenous veins: a large single-center
      experience.
AB  - PURPOSE: To evaluate the effectiveness of endovenous treatment of symptomatic
      varicose veins using the endovenous laser (EVL) or radiofrequency (RF) energy
      over a >3-year follow-up. METHODS: From February 2002 to August 2005, 981
      consecutive patients (770 women; mean age 51 years, range 15-90) with symptomatic
      varicose veins in 1250 lower limbs underwent endovenous ablation of 1149 great
      saphenous veins (GSV) and 101 small saphenous veins (SSV) under tumescent
      anesthesia without intravenous sedation or regional anesthesia. There were 990
      GSV and 101 SSV procedures using EVL; 159 GSVs were treated with RF energy. An
      ultrasound evaluation was performed within 2 weeks of the procedure to evaluate
      occlusion of the vein, wall thickness, and clot extension into the deep venous
      system. Follow-up from the first 200 procedures in the series included clinical
      evaluation and duplex ultrasound scanning at 6 and 12 months and annually
      thereafter. RESULTS: Of the 1149 GSVs treated, 39 (3.4%) recanalizations were
      seen in 33 of the EVL and 6 of the RF procedures for inadequate treatment as
      judged by ultrasound. There were 9 (9.0%) failures among the 101 SSVs treated
      with EVL. Overall, both EVL and RF procedures were well tolerated, with only
      minor complications. One obese patient with ulcer developed pulmonary embolus on
      the fourth postoperative day. There were no differences between EVL and RF in
      efficacy or complications. Follow-up at a mean 3 years (range 30- 42 months) in
      143 treated limbs showed no neovascularization in the groin. CONCLUSION: Outcomes
      with EVL and RF were good, with low complication rates that may be related to the
      use of local tumescent anesthesia without intravenous sedation.

PMID- 16643081
TI  - Endovascular recanalization of chronic long-segment occlusions of the inferior
      vena cava: midterm results.
AB  - PURPOSE: To report the midterm results of endovascular recanalization of chronic
      long-segment (> 5 cm) occlusions of the inferior vena cava (IVC) with stent
      placement. METHODS: Nine patients (5 men; median age 30 years, range 14-58) with
      disabling complaints for more than 6 months caused by IVC occlusions were treated
      by endovascular recanalization. Mean occlusion length was 11 cm (range 6-22);
      some occlusions extended to the iliac (n = 3) or common femoral (n = 2) veins.
      All procedures were performed under local anesthesia via a bilateral femoral (n =
      7) or popliteal (n = 2) approach. In 3 patients, combined access to the brachial
      or internal jugular vein was necessary. Patients with acute-on-chronic thrombosis
      were pretreated with urokinase. After guidewire recanalization, the chronic
      occlusions were predilated and self-expanding Wallstents were implanted. RESULTS:
      The initial technical and clinical success was 100%. The venous clinical severity
      score (pain, venous edema, inflammation, and active ulceration) decreased from a
      mean 8 +/- 2 to 5 +/- 1 after the procedure. Over a median follow-up of 9 months
      (mean 21, range 4- 110), 3 patients died. One rethrombosis occurred, and an
      asymptomatic restenosis was discovered on routine imaging. The primary patency
      rate was 78%, and the 9-month occlusion-free survival rate was 56%. CONCLUSION:
      Endovascular recanalization of chronic long-segment occlusions of the IVC is a
      safe and worthwhile technique to offer patients with debilitating symptoms.

PMID- 16643082
TI  - Successful stenting seven days after atherothrombotic occlusion of the
      intracranial internal carotid artery.
AB  - PURPOSE: To report a case of successful stenting after a subacute stroke. CASE
      REPORT: A 75-year-old man presented with sudden onset of right-sided weakness and
      difficulty speaking. Imaging revealed an occlusion of the left petrous to lacerum
      internal carotid artery (ICA) segment and slightly decreased cerebral blood flow
      in the left hemisphere; there were stenoses of the ostial and cavernous ICA
      segments on the right. On the seventh day after the stroke, he underwent
      protected carotid angioplasty of the left intracranial ICA occlusion to reduce
      the high risk of ischemic stroke owing to bilateral disease. An external
      arteriovenous shunt was established with an occluding balloon in the proximal ICA
      and a filter in the femoral vein. After protected balloon dilation of the ICA
      occlusion, a 3.5 x 18-mm balloon-expandable coronary stent was deployed across
      the residual stenotic segment. An intraluminal filling defect of the petrous ICA
      segment suggested an arterial dissection or intraluminal thrombus, so another 2
      coronary stents were deployed. Macroscopically visible materials were captured in
      the filter. The patient had a good clinical course and was discharged without
      neurological deficits on the twelfth day after the stroke. Angiography at 3
      months confirmed no restenosis of the stented vessel. CONCLUSION: This experience
      suggests that short atherothrombotic intracranial ICA occlusions can be opened in
      the subacute stroke stage without distal migration of thrombi under proximal
      protection and flow reversal.

PMID- 16643083
TI  - Renal allograft laceration treated by superselective embolization.
AB  - PURPOSE: To report an illustrative case demonstrating the efficacy of
      endovascular treatment for traumatic blunt renal allograft injury. CASE REPORT: A
      19-year-old man sustained an injury to his renal allograft after a traffic
      accident secondary to lap belt compression. Angiography revealed contrast
      extravasation from 2 disrupted upper pole renal artery branches, which were
      successfully embolized with microcoils. The creatinine level was transiently
      elevated to 4.1 mg/dL, but it improved to 2.9 mg/dL at discharge 13 days after
      admission. After 1 year, the serum creatinine level was 1.9 mg/dL. CONCLUSION: As
      in the native kidney, superselective embolization can also be used safely in the
      management of blunt injury to a renal allograft, avoiding surgery and preserving
      graft function.

PMID- 16643084
TI  - Percutaneous repair of abdominal aortic pseudoaneurysm by catheter-based delivery
      of thrombin.
AB  - PURPOSE: To present a case in which thrombin was injected percutaneously to treat
      an aortic pseudoaneurysm. CASE REPORT: A 63-year-old man developed a large
      pseudoaneurysm in the abdominal aorta after surgical fenestration and patch
      aortoplasty for acute type B aortic dissection with malperfusion syndrome.
      Transcatheter delivery of 1500 units of thrombin resulted in complete thrombosis
      of the pseudoaneurysm sac. No complications occurred. Twelve months after the
      procedure, the pseudoaneurysm was completely resolved on computed tomography.
      CONCLUSION: Thrombin continues to prove its safety and efficacy for the treatment
      of pseudoaneurysms at numerous anatomical sites, including the abdominal aorta.

PMID- 16643085
TI  - UV radiation as a potential driving force for zooplankton community structure in
      Patagonian lakes.
AB  - This article explores the potential role of UV radiation (UVR) as an influence on
      zooplankton communities. In the first section we provide a general overview of
      UVR effects on freshwater zooplankton, with an emphasis on Argentine and Chilean
      environments. In the second section we present the results of a survey involving
      53 temperate lakes across a gradient of UVR exposure to determine patterns of
      species richness and specific diversity. These community characteristics
      decreased at high potential UVR exposure (i.e. high mean water column irradiance
      or low lake optical density). A threshold value of mean water column irradiance
      of approximately 10% of the surface level seems to limit both richness and
      diversity to minimum values. On the basis of the collected evidence it is not
      possible to definitely conclude that UVR rather than another covarying factor is
      responsible for the decrease in specific diversity observed at the lowest end of
      lake optical depth. However, lakes with values above the previous threshold are
      likely to exhibit highly depauperate zooplankton communities regardless of the
      mechanism. As a cautionary note we suggest that changes in the optical
      characteristics (i.e. changes due to atmospheric conditions, precipitation
      patterns or vertical displacement of the tree line) may result in sudden shifts
      in zooplankton community structure.

PMID- 16643086
TI  - Ultraviolet B-photoprotection efficiency of mesocosm-enclosed natural
      phytoplankton communities from different latitudes: Rimouski (Canada) and Ubatuba
      (Brazil).
AB  - Photoprotection against UV-B radiation (UVBR; 280-320 nm) was examined in natural
      phytoplankton communities from two coastal environments at different latitudes:
      temperate Rimouski (Canada) and tropical Ubatuba (Brazil). Mesocosm experiments
      were performed at these sites to examine the response of phytoplankton to
      increases in UVBR that corresponded to local depletions of 30% and 60% in
      atmospheric ozone levels (low and high UVBR treatments, respectively). A
      fluorescence method using a pulse amplitude modulation fluorometer (Xe-PAM, Walz,
      Germany) with selective UV filters was used to estimate photoprotection, and
      these results were compared with an index of mycosporine-like amino acid (MAA)
      concentrations determined using spectrophotometry of methanol extracts. The
      present study provided the first evidence, to our knowledge, of the suitability
      of this in vivo fluorescence method for the estimation of UV photoprotection
      efficiency in natural phytoplankton. No significant differences were found for
      most of the variables analyzed between the light treatments used at both sites,
      but differences were found between sites throughout the duration of the
      experiments. Vertical mixing, used to maintain cells in suspension, likely
      alleviated serious UVBR-induced damage during both experiments by reducing the
      length of time of exposure to the highest UVBR irradiances at the surface. In
      Rimouski, this was the main factor minimizing the effects of treatment, because
      optical properties of the coastal seawater rapidly attenuated UVBR throughout the
      water column of the ca 2 m deep mesocosms. In this location, synthesis of MAAs
      and photoprotective pigments likely contributed to the observed phototolerance of
      phytoplankton and, hence, to their growth; however, in a comparison of the UVBR
      treatments, these variables showed no differences. In Ubatuba, where nutrient
      concentrations were significantly lower than those in Rimouski, light attenuation
      was less than that in Rimouski and UVBR reached the bottom of the mesocosms. UVBR
      penetration and the forced vertical mixing of the cells, without the possibility
      of vertical migration below this photostress zone, resulted in photo-inhibition,
      because confinement in the mesocosms forced cells to remain constantly exposed to
      high levels of irradiance during the daytime. Hence, additional effects of UVBR
      were masked in this experiment, because cells were damaged too much and
      phytoplankton populations were rapidly declining. There was also an overall
      preservation of MAAs, in contrast with chlorophyll (Chl) degradation, in spite of
      the fact that this UV screening was not sufficient to counteract photo
      inhibition, which suggests an important role for these molecules, either in the
      overall photoprotection strategy or in other physiological processes. Altogether,
      local water characteristics, namely attenuation, mixing, and nutrients
      concentration, can strongly modulate the photoprotection strategies used by
      natural phytoplankton populations in coastal environments.

PMID- 16643087
TI  - Application of time-resolved polarization fluorescence spectroscopy in the
      femtosecond range to photosynthetic systems.
AB  - Time-resolved polarization fluorescence spectroscopy in the femtosecond range was
      applied to a photosynthetic antenna system. Specific signals of excited states
      were obtained by simultaneous measurements of fluorescence rise and decay curves
      and polarized spectroscopy. Relaxation processes of carotenoids, energy transfer
      from carotenoids to chlorophyll (Chl) a, and energy migration among pigment pools
      of Chl a and Chl b were clearly resolved. Two new characteristics of carotenoid
      molecules were revealed only by anisotropy measurements. A new singlet excited
      state between the well known S2 (1Bu(+)) and S1 (2Ag(-)) states was resolved by
      an intermediary anisotropy (r(t) = 0.30) for siphonaxanthin in chloroplasts of
      Codium fragile. Time-dependent changes in anisotropy with an initial value of
      0.52 (r(0) = 0.52) were recorded during the relaxation of lutein molecules in the
      light-harvesting complexes II of Arabidopsis thaliana, and this was interpreted
      as a strong interaction between two lutein molecules in the pigment-protein
      complexes. Other examples of the application of this method were also discussed.

PMID- 16643088
TI  - Overview of theoretical and computational methods applied to the oxygen-organic
      molecule photosystem.
AB  - The challenges of using modern theoretical and computational tools to model the
      unique features of the oxygen-organic molecule photosystem are discussed from a
      historical and pedagogical perspective. This review is written for the novice,
      but the problems formulated should stimulate the expert.

PMID- 16643089
TI  - A feature-tracking model simulates the motion direction bias induced by phase
      congruency.
AB  - Here we report a new motion illusion where the prevailing motion direction is
      strongly influenced by the relative phase of the harmonic components of the
      stimulus. The basic stimulus is the sum of three sinusoidal contrast-reversing
      gratings: the first, the third, and the fifth harmonic of two square wave
      gratings that drift in opposite direction. The phase of one of the fifth
      components was kept constant at 180 deg, whereas the phase of the other fifth
      harmonic was varied over the range 0-150 deg. For each phase value of the fifth
      harmonic, the motion was strongly biased toward its direction, corresponding to
      the direction with stronger phase congruency between the three harmonics. The
      strength of the prevailing motion was assessed by measuring motion direction
      discrimination thresholds, by varying the contrast of the third and the fifth
      harmonics plaid pattern. Results show that the contrast of high harmonics had to
      be increased by more than a factor of 10, to achieve a balance of motion for
      phase differences greater than 60 deg between the 2 fifth harmonics. We also
      measured the dependence on the absolute phase of harmonic components and found
      that it is not an important parameter, excluding the possibility that local
      luminance cues could be mediating the effect. A feature-tracking model based on
      previous work is proposed to simulate the data. The model computes local energy
      function from a pair of space-time separable front stage filters and applies a
      battery of directional second stage mechanisms. It is able to simulate
      quantitatively the phase congruency dependence illusion and the insensitivity to
      overall phase. Other energy models based on directional filters fail to simulate
      the phase congruency dependency effect.

PMID- 16643090
TI  - Dynamics of attentional deployment during saccadic programming.
AB  - The dynamics of attentional deployment before saccade execution was studied with
      a dual-task paradigm. Observers made a horizontal saccade whose direction was
      indicated by a symbolic precue and had to discriminate the orientation of a Gabor
      patch displayed at different delays after the precue (but before saccade onset).
      The patch location relative to the saccadic target was indicated to observers
      before each block. Therefore, on each trial, observers were informed
      simultaneously about the respective absolute locations of the saccadic and
      perceptual targets. The main result is that orientational acuity improved over a
      period of 150-200 ms after the precue onset at the saccadic target location,
      where overall performance is best, and at distant locations. This effect is due
      to attentional factors rather than to an alerting effect. It is also dependent on
      the efficiency of the temporal masks displayed before and after the Gabor
      patches.

PMID- 16643091
TI  - Advantages and disadvantages of human dichromacy.
AB  - We compared the visual detection thresholds for cone-isolating stimuli of
      trichromats (those with normal color vision) with those of X-linked dichromats,
      who lack either the long-wavelength-sensitive (L) cones (protanopes) or middle
      wavelength-sensitive (M) cones (deuteranopes). At low (1 Hz) temporal
      frequencies, dichromats have significantly higher (twofold) thresholds for all
      colored stimuli than trichromats; whereas at high (16 Hz) temporal frequencies,
      they perform as well or better than trichromats. The advantages of dichromats in
      detecting high temporally modulated targets can be related to an increased
      number, through replacement, of the remaining L- or M-cone type. However, their
      disadvantages in detecting low temporally modulated targets, even in directions
      of color space where their increased number of cone photoreceptors might be
      expected to be beneficial, are best explained in terms of the loss of L-M cone
      opponency and the inability of the visual pathways to reorganize to allow the
      detection of low-frequency luminance modulation.

PMID- 16643092
TI  - The effect of spatial configuration on surround suppression of contrast
      sensitivity.
AB  - Contrast sensitivity is known to be strongly influenced by the target surround,
      yet the role of the surround interaction in visual processing remains unclear.
      Previously, we have shown that the surround strongly suppresses contrast
      sensitivity in the periphery when the surround spatial frequency and orientation
      match those of the target (Petrov, Carandini, & McKee, 2005). Here, we explore
      how various spatial characteristics of the iso-oriented and frequency-matched
      surround, such as surround phase and spatial layout, affect suppression. We
      manipulated surround geometry (annulus ring, half annulus, and bow tie) and its
      separation from the target (both laterally and in depth) and varied the position
      of the half-annulus and bow-tie surrounds with respect to Gabor target's
      orientation and with respect to its location in the visual field (i.e., radial
      vs. tangential surrounds). We also compared monoptic, dichoptic, and binocular
      surround suppression. Except for a significant radial-tangential anisotropy, only
      the area of the surround and the lateral separation between the surround and
      target had a significant effect on the magnitude of suppression. We showed that,
      although suppression amplitude remains constant with stimulus eccentricity, the
      lateral extent of suppression scales in proportion to the eccentricity. The most
      surprising finding was that the extent of surround suppression does not scale
      with stimulus size or spatial frequency. We suggest that the properties of
      surround suppression are best explained by a mechanism that selects salient
      targets for subsequent saccades.

PMID- 16643093
TI  - Higher level chromatic mechanisms for image segmentation.
AB  - We used a noise-masking paradigm to investigate the number and properties of
      chromatic mechanisms involved in image segmentation. Observers were presented
      with a pattern of dynamic random squares, each independently modulated along a
      certain direction in DKL color space, either in the isoluminant plane or in the L
      - M luminance plane. A signal consisting of a rectangular region of squares,
      oriented horizontally or vertically, was added to the noise. The signal squares
      were spatially and temporally aligned to the noise squares, excluding the
      possibility of phase offsets to mediate segmentation performance. Noise and
      signal color directions were independently varied, and the signal contrast was
      measured at which an observer could reliably indicate the orientation of the
      signal. In a second set of experiments, the noise was simultaneously varying in
      two directions, symmetrically arranged around the signal direction. Masking was
      generally highest when signal and noise were modulated along the same direction
      and minimal for orthogonal noise. No difference was found between signals
      modulated along cardinal directions or intermediate directions. However, measured
      tuning widths critically depended on the type of noise: Noise modulated along one
      direction results in narrow tuning, whereas two-sided noise results in broad
      tuning. A chromatic detection model with multiple broadly tuned mechanisms
      successfully accounts for the experimental findings, both for narrow and broad
      tuning curves. Models with four broadly tuned cardinal mechanisms or multiple
      narrowly tuned mechanisms failed to reproduce the data. Our results suggest an
      important role for multiple, broadly tuned mechanisms in image segmentation.

PMID- 16643094
TI  - Perceptual synchrony of audiovisual streams for natural and artificial motion
      sequences.
AB  - We investigated the conditions necessary for perceptual simultaneity of visual
      and auditory stimuli under natural conditions: video sequences of conga drumming
      at various rhythms. Under most conditions, the auditory stream needs to be
      delayed for sight and sound to be perceived simultaneously. The size of delay for
      maximum perceived simultaneity varied inversely with drumming tempo, from about
      100 ms at 1 Hz to 30 ms at 4 Hz. Random drumming motion produced similar results,
      with higher random tempos requiring less delay. Video sequences of disk stimuli
      moving along a motion profile matched to the drummer produced near-identical
      results. When the disks oscillated at constant speed rather than following
      "biological" speed variations, the delays necessary for perceptual synchrony were
      systematically less. The results are discussed in terms of real-world constraints
      for perceptual synchrony and possible neural mechanisms.

PMID- 16643095
TI  - Feature-based attentional integration of color and visual motion.
AB  - In four variants of a speeded target detection task, we investigated the
      processing of color and motion signals in the human visual system. Participants
      were required to attend to both a particular color and direction of motion in
      moving random dot patterns (RDPs) and to report the appearance of the designated
      targets. Throughout, reaction times (RTs) to simultaneous presentations of color
      and direction targets were too fast to be reconciled with models proposing
      separate and independent processing of such stimulus dimensions. Thus, the data
      provide behavioral evidence for an integration of color and motion signals. This
      integration occurred even across superimposed surfaces in a transparent motion
      stimulus and also across spatial locations, arguing against object- and location
      based accounts of attentional selection in such a task. Overall, the pattern of
      results can be best explained by feature-based mechanisms of visual attention.

PMID- 16643096
TI  - Are cone sensitivities determined by natural color statistics?
AB  - We investigate how the amount of information about colors in natural scenes
      available to the visual system depends on the spectral sensitivities of the three
      types of cones. We find that if we do not consider spatial information and low
      signal-to-noise situations, human cone spectral sensitivity curves do not provide
      the maximum possible information. This applies not only to information about all
      colors in natural scenes, but equally to information about colors of edible
      fruit. However, a significant increase in color information could only be
      obtained if the L-cone was sensitive to even longer wavelengths, at the expense
      of a reduction in spatial acuity and in the information available in dim lighting
      conditions.

PMID- 16643097
TI  - Development of an obesity prevention and management program for children and
      adolescents in a rural setting.
AB  - This study applied theory-based health behavior change constructs to childhood
      obesity prevention. Constructs such as goal setting, self-efficacy, and readiness
      for change were used within a rural community-based program designed to be
      developmentally appropriate for 6th graders. The project included 2 studies
      across 12 months. The 1st assessed the scope of the obesity problem within a 3
      county area with key stakeholders in health and education. The 2nd implemented a
      pilot community intervention program within a rural middle school. Participants
      in the intervention included 65 middle-school students and the families of 25 of
      these students. Qualitative and quantitative analyses were conducted to assess
      the effectiveness of the intervention. Changes from pre- to postintervention on
      relevant measures were statistically significant for families but not for
      students. Issues related to family versus individual behavior change are
      discussed, along with implications for managing behaviorally based activity and
      nutrition interventions within a rural community.

PMID- 16643098
TI  - Parent-child communication: a model for Hispanics on HIV prevention.
AB  - The prevalence of Acquired Immunodeficiency Syndrome has become a global epidemic
      that has affected many different racial and ethnic groups. One group that has
      lacked attention is the Hispanic population, due to its distinctive cultural
      characteristics. Many of the Human Immunodeficiency Virus (HIV) infections in
      Hispanics occur in adolescents. A protective factor for preventing HIV infections
      in adolescents is parent-child communication about sexual intercourse; however
      discussions about sexuality are uncommon in Hispanic families. When promoting
      parent-child communication among Hispanics regarding sex, it is essential to
      include cultural characteristics and the use of a model for empowering both
      parents and adolescents. The cultural characteristics examined in this article
      are allocentrism, familialism, personal space, time orientation, power distance,
      gender roles, and fatalism. A partnership model for empowering parents and
      adolescents, and 5 steps of the partnership process are discussed.

PMID- 16643099
TI  - Addressing domestic violence through maternal-child health home visiting: what we
      do and do not know.
AB  - Domestic violence (DV) has been described as a public health epidemic. Health
      care providers of all disciplines encounter victims of DV in every practice
      setting. However, the vast majority of DV health care research has focused on
      care provided to victims in traditional acute care and clinic settings. Few
      investigators have conducted studies with community health nurses (CHNs) who
      visit DV victims in their homes. CHNs, providing preventive maternal-child health
      (MCH) care through home visits with families, have been described by some as key
      providers in DV prevention. However, there is a dearth of knowledge about the
      actual practice and related outcomes of these nurses when working with families
      experiencing DV. The purpose of this article is to provide a baseline view of the
      current state of knowledge on which nurses may begin building future research
      that leads to evidence-based practice. The article describes the potential role
      of home-visiting MCH nurses in DV prevention and intervention, provides a
      critical review of the existing research, identifies primary gaps in scientific
      knowledge, proposes future research priorities, and makes recommendations for
      practice.

PMID- 16643100
TI  - Ecological influences of sexuality on early adolescent African American females.
AB  - African Americans make up the greater proportion of AIDS cases in adolescent
      girls but little is understood about the development of sexual risk behaviors
      during the early adolescent years. This article will explore ecological factors
      influencing adolescent sexual risk behaviors. In the focus groups, which were
      conducted using 28 African American mothers and their early adolescent daughters,
      2 major themes emerged: exposure and support systems. Mothers described the
      impact community had on their daughters and how monitoring and support systems
      worked together to control exposure. The girls detailed the different ways they
      were impacted by the community. Attitudes the girls adopted from their exposures
      resulted in risk-taking behaviors or a determination to positively impact the
      community. Community was shown to be the context of the acquisition of sexual
      knowledge and attitudes. These findings support the development of interventions
      to address the impact of community on the participation of sexual risk behaviors.

PMID- 16643101
TI  - Red flags during home visitation: infants and toddlers.
AB  - High-risk families remain a challenge for all who provide community-based health
      services, particularly home visitations. The purpose of this article is to
      describe red flags, that is, any physical, developmental, or psychosocial
      findings identified during a home visit that require further evaluation or
      referral. The red flags were developed to increase the community-based provider's
      ability to assess the health status of children and to support efforts to provide
      home intervention services for children at risk for abuse and neglect. These red
      flags are useful to nurses working in collaboration with nonnursing professionals
      providing home visits.

PMID- 16643105
TI  - Specters of democracy: dense objects and states of mourning.

PMID- 16643106
TI  - Why does religion turn violent? A psychoanalytic exploration of religious
      terrorism.

PMID- 16643107
TI  - Terror and truth.

PMID- 16643108
TI  - Fundamentalism, father and son, and vertical desire.

PMID- 16643109
TI  - Narcissism, sexuality, and psyche in terrorist theology.

PMID- 16643110
TI  - Bible says: the psychology of Christian fundamentalism.

PMID- 16643111
TI  - On the psychology of violent Christian fundamentalism: fighting to matter
      ultimately.

PMID- 16643112
TI  - Fundamentalism, psychoanalysis, and psychoanalytic theories.

PMID- 16643115
TI  - Introduction to the special section: Philosophy and personality disorders.

PMID- 16643116
TI  - Moral nature of the DSM-IV Cluster B personality disorders.
AB  - Moral considerations do not appear to play a large role in discussions of the DSM
      IV personality disorders and debates about their empirical validity. Yet
      philosophical analysis reveals that the Cluster B personality disorders, in
      particular, may in fact be moral rather than clinical conditions. This finding
      has serious consequences for how they should be treated and by whom.

PMID- 16643117
TI  - Person, personality, self, and identity: a philosophically informed conceptual
      analysis.
AB  - Who is the person, or self, associated with personality disorder and its
      treatment? How are we to account for a self conceptualized in terms of schemas
      and representations, that at the same time--as self--scrutinizes these schemas
      and representations (as in cognitive therapy for personality disorders)? Five
      approaches to personhood are examined: metaphysical, empirical, transcendental,
      hermeneutical, and phenomenological. An elementary sense of selfhood is tied to
      all one's experiences and activities; this sense of self is experientially
      irreducible and conceptually connected to a primordial form of self-relatedness.
      After examining these issues, I formulate four provisional conclusions: (a) the
      separation between person and roles (functions, personality features) is a modern
      fiction--persons are not neutral bearers of roles and functions; (b) the concept
      of personality in DSM-IV refers to nonhomogeneous behaviors such as feelings,
      moods, inclinations, temperaments, and habits, and these behaviors differ with
      respect to their distance to the core self; (c) there exists an enormous variety
      of ways of self-relating and this variety may affect the contents of the core
      self under certain circumstances; and (d) the concept of person may be primitive;
      that is, irreducible and referring to a background of unity and integrity.

PMID- 16643118
TI  - What is manipulative behavior, anyway?
AB  - One of the most common ways of characterizing patients diagnosed with borderline
      personality disorder is that they are manipulative. Clinical usage of the term
      varies widely but clearly carries a pejorative meaning. Furthermore, behaviors
      that look similar to those called manipulative in clinical contexts are not
      called manipulative in broader society. It is crucial to become clear on what
      manipulation is, because studies show that carers routinely perceive BPD patients
      as manipulative and so have less empathy for them. In this paper the concept of
      manipulativity is clarified and its scope narrowed by distinguishing it from a
      number of related concepts, and a number of reasons why manipulating others is
      morally objectionable are suggested. I argue that, while some BPD patients may be
      manipulative, much of their behavior can and should be understood in a different
      light. Moral and clinical values are conflated in carers' judgments of
      manipulativity, and clinicians and researchers need to clarify when and why
      manipulative behavior is dysfunctional, and when it is merely morally wrong.
      Separating these two domains will enable carers to be more empathetic and less
      blaming of their patients' behavior.

PMID- 16643119
TI  - Personality disorder as harmful dysfunction: DSM'S cultural deviance criterion
      reconsidered.
AB  - The DSM's general criteria for personality disorder (PD) attempt to define PD
      versus nondisordered personality conditions. If dimensionalization of PD occurs
      in the DSM-V (perhaps, it is suggested, with PD diagnosis moved to Axis I and
      overall personality assessment in Axis II, thus separating diagnosis from case
      formulation), general criteria likely will still be needed to prevent massive
      false positives. In this article, one of the general criteria, the cultural
      deviance requirement (CDR), is examined from the perspective of the evolution
      based harmful-dysfunction analysis of disorder. The CDR is often assumed to
      express value relativity of harm in diagnosis, but cultural values are a designed
      feature of human social functioning that influence personality formation. The CDR
      is thus argued to be an indicator of whether an individual's personality
      organization is due to an evolutionary dysfunction. Value relativity and
      evolutionary analysis thus converge.

PMID- 16643120
TI  - Normative warrant in diagnostic criteria: the case of DSM-IV-TR personality
      disorders.
AB  - This article focuses on the kinds of evaluative judgments made when applying DSM
      IV-TR diagnostic criteria within the diagnostic interview between clinician and
      patient. The authors name these kinds of value judgments in diagnosis "normative
      warrant" because they involve one or more justifications (warrants) for standard
      bearing (normative) elements involved in applying diagnostic criteria to actual
      patients. Seven types of normative warrant judgments are described (Type 1,
      Semantic-Phenomenal Matching; Type 2, Solicitation Choice; Type 3, Sociocultural
      Context; Type 4, Performance-Context Matching; Type 5, Deviance Threshold; Type
      6, Threshold Characterization; Type 7, Disvalue characterization) and the
      typology is illustrated by applying it to various DSM-IV-TR personality disorder
      criteria. A research and clinical understanding of normative warrant may well
      contribute to the refinement of criteria sets as well as the refinement of the
      clinical use of criteria sets.

PMID- 16643123
TI  - Confirmatory factor analyses of DSM-IV Cluster C personality disorder criteria.
AB  - Notwithstanding its research and clinical relevance, the dimensionality and
      validity of the DSM-IV avoidant, dependent, and obsessive-compulsive personality
      disorders (PDs) criteria is still a largely unexplored topic. The aim of this
      study was to test the factor structure for DSM-IV Cluster C PD criteria in a
      sample of 641 consecutively admitted outpatients. Factor analysis results
      suggested that avoidant, dependent, and obsessive-compulsive PDs share a common
      latent dimension, and supported the three-factor structure of both observer and
      self-report ratings of DSM-IV Cluster C PD criteria. The pattern of factor
      loadings, however, was different from the one expected according to the DSM-IV
      classification.

PMID- 16643124
TI  - Falling forever: the price of chronic shock.
AB  - Manifestations of chronic shock and annihilation anxiety-including autistic
      defenses, chaotic relationships, disorganized attachment, split-off affective
      states, and vulnerability to disintegration--exist side by side with apparent ego
      strength and high functioning, even in nonabused patients. Chronic shock stemming
      from uncontained distress and failed dependency during childhood can persist
      throughout the lifespan, creating ripples of dysfunction that mask as character
      distortion and contribute to therapeutic impasse. Patients rely on omnipotent
      defenses to provide a sense of "having skin" in the face of the fear of
      breakdown, striving to avoid vulnerability, and trying to insulate themselves
      from shock experience. Although the relinquishment of autistic defenses and
      subsequent integration of disowned affect states are overwhelming and painful,
      patients can emerge from this process with significant shifts in intrapsychic,
      interpersonal, and existential/spiritual functioning. Clinical material from one
      psychodynamic psychotherapy group tracks the group process and growth
      trajectories of seven group members struggling with chronic shock. The ability to
      recognize subtle dissociative states is a valuable tool in the repertoire of the
      group psychotherapist.

PMID- 16643125
TI  - Interpersonal feedback: a social relations perspective.
AB  - The social relations model (SRM; Kenny, 1994) is a statistical model for studying
      interpersonal perception and behavior that can be meaningfully applied to the
      group therapy situation. It consists of four primary components that correspond
      to (a) the general emotional or attitudinal climate of the group, (b) the
      perspective of the perceiver providing the feedback, (c) the group's consensual
      view of the target who receives the feedback, and (d) the unique relationship
      between the perceiver and the target. Because of its rigor and specificity, the
      components of the SRM may serve as a heuristic for thinking about interpersonal
      feedback in group therapy. A case example is used to demonstrate how an SRM
      perspective could guide therapists' ways of conceptualizing feedback.

PMID- 16643126
TI  - Use of the social relations model by group therapists: application and
      commentary.
AB  - This article presents research findings concerning the relationship of patient
      positive regard to the outcome of time-limited, short-term group therapy for
      psychiatric outpatients with complicated grief. The Social Relations Model
      (SOREMO) of David Kenny was used to investigate this relationship. While the
      patient's ratings of positive regard of others in the group, known as the
      Perceiver Effect, accounted for the most variation of the patients' ratings, the
      other patients' rating of the patient's positive regard, known as the Target
      Effect, was directly related to favorable change. In addition, a simpler method
      was used to calculate variables that were analogous to the Perceiver Effect and
      Target Effect variables of the SOREMO. These variables yielded similar outcome
      findings. Because of limitations and difficulties associated with learning and
      using the SOREMO, the simpler method represents a more feasible choice for group
      therapists who are primarily clinicians or group therapists who wish to collect a
      small amount of data on an ongoing basis. Even experienced group therapy
      researchers are likely to find the SOREMO program challenging to use.

PMID- 16643127
TI  - Don't fear the social relations model: reply to Piper, Ogrodniczuk, Lamarche, and
      Joyce.
AB  - By studying actual therapy groups and using a sophisticated design to determine
      that clients who are held in higher esteem by their fellow group members show
      greater improvement over the course of therapy, Piper, Ogrodniczuk, Lamarche, and
      Joyce (this issue) have made a significant contribution to the group
      psychotherapy literature. Unfortunately, Piper et al. focused much of their
      discussion on the difficulties they faced using the social relations model (SRM)
      and the statistical program SOREMO. Although the SRM is not simple and it takes
      practice to run SOREMO, the analytic alternative proposed by Piper et al. has a
      number of serious limitations that prevents it from being a viable alternative.
      There is much to be gained from learning the SRM; for those group therapists and
      researchers who do not want to learn the SRM, they can always consult or
      collaborate with SRM researchers.

PMID- 16643128
TI  - Forty years of group psychotherapy at the Menninger Clinic.
AB  - Despite the skepticism and indifference to group psychotherapy that existed in
      the 1950s and 1960s within the psychoanalytic community in general and among the
      staff and administration of the Menninger Clinic in Topeka, Kansas in particular,
      a few clinicians there forged ahead in pursuit of incorporating this modality as
      an accepted treatment. After gaining some acceptance first in the hospital, we
      experienced a slow rate of growth, except with our trainees who were generally
      enthusiastic about group work. Many of them were intrigued first by their
      exposure to the group dynamics seminars and later by the didactic courses and
      supervised group work that eventually came to be required by the accrediting body
      for residency programs of the American Psychiatric Association. Visiting senior
      consultants and teachers, mainly associated with the American Group Psychotherapy
      Association, as well as an esteemed clinician from the Tavistock Clinic, also
      lent credibility and legitimacy to our effort. When group treatment began to be
      adopted by units of the Menninger Hospital in the early 1970s, there was a
      significant sea change in the attitude of the organization and group
      psychotherapy became a well established modality.

PMID- 16643131
TI  - Necrotizing fasciitis: a deadly infection.
AB  - Necrotizing fasciitis (NF) is a life-threatening condition, consisting of a soft
      tissue infection with rapidly progressive, widespread fascial necrosis. NF may be
      caused by a wide variety of microbes. Indeed, NF may be an infection of one
      species of bacteria or may be polymicrobial. Prompt diagnosis and treatment are
      essential. Surgical debridement and antibiotic therapy are the primary treatment
      options.

PMID- 16643132
TI  - Adherence to treatment in patients with psoriasis.
AB  - Non-adherence to medication is a chronic problem that impacts on healthcare
      professionals and patients alike. In psoriasis, a condition that presents
      patients with frequent and disabling physical, psychological and social effects,
      studies consistently suggest that up to 40% of patients do not use their
      medication as directed. Thus it is probable that poor adherence contaminates the
      clinical picture of response effectiveness in everyday practice. This educational
      paper reviews research that investigates adherence to medication in patients with
      psoriasis. It provides an overview of contributing factors and mediating
      variables. It is proposed that three specific facets appear to optimize patient
      adherence: an effective doctor-patient relationship; optimism with the treatment
      prescribed; and a limited 'nuisance' value of treatment in terms of side-effects
      and hassle of use. Various strategies to address adherence are suggested and it
      is argued that in order to enhance our understanding of adherence in patients
      with psoriasis, there needs to be an increasing focus on patients' beliefs about
      their condition and its management.

PMID- 16643133
TI  - Self-reported skin sensitivity in a general adult population in France: data of
      the SU.VI.MAX cohort.
AB  - OBJECTIVE: This study aimed to examine the frequency of self-assessed facial skin
      sensitivity and its different patterns, and the relationship with gender and sun
      sensitivity in a general adult population. METHODS: A standardized 11-item
      questionnaire investigating reactions experienced during the past year was
      developed. The questions explored different patterns of skin sensitivity: pattern
      I (blushing related to vascular reactivity), pattern II (skin reactions to
      certain environmental conditions), pattern III (skin reactions after substance
      contact), and for women pattern IV ('breakout of spots' related to menstrual
      cycle). Additional items were addressed for women and men, including sun
      sensitivity. The questionnaire was administered to a large middle-aged population
      involved in the 'Supplement en Vitamines et Mineraux Antioxydants' (SU.VI.MAX)
      cohort. RESULTS: Sensitive facial skin was reported by 61% of the women (n =
      5074) and 32% of the men (n = 3448), and the frequency decreased with age. The
      frequency of patterns I, II and III was greater for women (78, 72 and 58%,
      respectively) than for men (56, 48 and 28%) of comparable classes of age. The
      frequency of pattern IV was reported by 49% of premenopausal women, and skin
      reactions after shaving by 41% of the men. Sun sensitivity was found to be a
      major component of skin sensitivity. Factor analysis showed that individuals with
      fair phototype frequently evoked reactions associated with pattern I, and skin
      redness and burning sensations were related to certain environmental conditions
      (pattern II). CONCLUSION: Skin sensitivity is a common concern that declines with
      age and is relevant for men as well as for women.

PMID- 16643134
TI  - Peripheral insulin resistance in patients with Behcet's disease.
AB  - In this study, we examined peripheral insulin resistance in patients with
      Behcet's disease (BD) characterized by chronic inflammation and endothelial
      dysfunction. Fourteen patients with BD and 15 healthy controls were recruited to
      the study. Insulin resistance was investigated by the hyperinsulinaemic
      euglycaemic glucose clamp technique. BD patients displayed an enhanced rate of
      insulin resistance compared to healthy controls (P = 0.014). The insulin
      sensitivity (M), measured as the glucose utilization rate under steady-state
      conditions of euglycaemia, was significantly decreased (P = 0.001) in BD patients
      compared to the controls (4.09 +/- 0.16 vs. 5.60 +/- 0.27 mg/kg/min). The C
      reactive protein (CRP) level, but not the erythrocyte sedimentation rate (ESR),
      was significantly related to the presence of insulin resistance (CRP: r(s) =
      0.589, P = 0.27; ESR: r(s) = 0444, P = 0112), whereas no relationship was found
      between the M-value and ESR or CRP. We conclude that patients with BD exhibit
      peripheral insulin resistance; this could be explained as the diverse
      consequences of inflammation and endothelial dysfunction in BD.

PMID- 16643135
TI  - Introducing a fast and simple PCR-RFLP analysis for the detection of mutant
      thiopurine S-methyltransferase alleles TPMT*3A and TPMT*3C.
AB  - BACKGROUND: Azathioprine, in combination with corticosteroids, is the first-line
      therapy of severe forms of pemphigus vulgaris. Patients with an impaired
      thiopurine S-methyltransferase (TPMT) activity are at risk of developing severe
      myelo-suppression upon treatment with thiopurines such as azathioprine. Analysis
      of the TPMT status prior to drug administration is therefore highly recommended.
      However, because of the limited availability of TPMT testing outside of
      specialized centres, pre-emptive TPMT testing is not widespread. To avoid
      laborious biochemical and sequencing assays, we evaluated a new restriction
      fragment length polymorphism (RFLP) analysis. METHODS: We designed a rapid
      genetic polymerase chain reaction (PCR)-RFLP screen for the most prevalent mutant
      TPMT*3A and TPMT*3C alleles that are known to result in reduced TPMT enzyme
      activity. RESULTS: Validating our fast system on 871 Caucasian DNA samples, we
      observed that 8.61% of our probands carried the TPMT*3A allele and 0.23% were
      heterozygous for the TPMT*3C allele, which is in concordance with previously
      reported allele frequencies. CONCLUSION: This simple and low-cost PCR-RFLP TPMT
      polymorphism testing approach can be performed in a standard laboratory. It
      should be applied to all patients prior to receiving thiopurine drug therapy to
      avoid the severe, but predictable, haematopoietic side-effects of thiopurine drug
      administration.

PMID- 16643136
TI  - Sweet's syndrome on the area of postmastectomy lymphoedema.
AB  - BACKGROUND: Sweet's syndrome (SS) has been reported in association with many
      conditions, including malignancy, infections, autoimmune disorders, pregnancy and
      drugs. MATERIALS AND METHODS: We reviewed patients with SS-like lesions on the
      lymphoedema area seen in our department. Clinical manifestations, histopathologic
      characteristics, treatment and outcome data were recorded and analysed. RESULTS:
      We report seven women with a history of surgery for breast cancer with axillary
      lymphadenectomy. Six of them were on tamoxifen. All of them had various lesions
      consistent with SS localized predominantly on the limb affected by the
      postmastectomy lymphoedema, and on the ipsilateral chest, trunk and back. One of
      them presented bullous lesions. Three of the cases underwent spontaneous
      remission, two resolved with antibiotic therapy, one healed with corticosteroids,
      and one with corticosteroids plus antibiotic. CONCLUSIONS: Erythematous tender
      plaques on the area of postmastectomy lymphoedema could be considered an unusual
      manifestation of Sweet's syndrome. We have found only three similar cases in the
      literature. Although it is difficult to elucidate the pathogenesis of this
      entity, it has been suggested that it could be due to immune surveillance
      impairment.

PMID- 16643137
TI  - Pinpoint papular variant of polymorphous light eruption: clinical and
      pathological correlation.
AB  - BACKGROUND: Polymorphous light eruption (PMLE) is the most common chronic
      idiopathic photodermatosis usually manifesting as a papular eruption along with
      several other morphological variants including a pinpoint papular variant.
      METHODS AND MATERIALS: Between June 1998 and August 2003, 10 PMLE patients
      presented to the Department of Dermatology at Henry Ford Hospital with complaints
      of a pruritic pinpoint papular eruption associated with sun exposure. In six
      patients skin biopsies were performed along with a detailed history and complete
      skin examination. We correlated the histology with the clinical course of disease
      corresponding to acute and subacute disease presentation. We also performed
      immunohistochemistry on three cases to study the immunophenotype in PMLE.
      RESULTS: The clinical, histologic and immunostain findings are summarized. Acute:
      Clinically pinpoint papules and vesicles, some with erythematous base, were seen.
      Histology showed focal vesicle formation, spongiosis, oedema, red blood cells
      extravasation, and superficial and deep perivascular and interstitial lymphocytic
      infiltrate with occasional eosinophils. Subacute: Clinically pinpoint papules
      with or without erythema were seen. Histology of the pinpoint lesion showed a
      nodular collection of lymphocytes and histiocytes with claw-like extension of
      epidermal rete ridges at the lateral boundaries of the lesion. Overlying
      epidermal atrophy with adjacent spongiosis, exocytosis, oedema and a superficial
      perivascular lymphocytic infiltrate and parakeratosis was also observed. The
      histologic differential diagnosis included lichen nitidus. Immunohistochemical
      stains revealed the following results: CD8, CD68 positive, CD4 variable (strongly
      positive to negative) and S-100 negative. CONCLUSION: (i) Pinpoint papular
      variant of PMLE is a distinct entity, which shows characteristic histology
      corresponding to the clinical course of the disease (acute and subacute). (ii)
      The histologic and immunophenotypic differential diagnosis of this variant during
      the subacute phase includes lichen nitidus.

PMID- 16643138
TI  - Rocky Mountain spotted fever.
AB  - Rocky Mountain spotted fever (RMSF) is an unusual but important dermatological
      condition to identify without hesitation. The classic triad of headache, fever,
      and a rash that begins on the extremities and travels proximally to involve the
      trunk is found in a majority of patients. The cutaneous centripetal pattern is a
      result of cell to cell migration by the causative organism Rickettsia rickettsii.
      Such individuals should receive prompt antimicrobial therapy and supportive care
      to avoid serious and potentially fatal complications.

PMID- 16643139
TI  - Familiar and environmental factors influencing atopic dermatitis in the
      childhood.
AB  - BACKGROUND: The increase in the incidence of atopic dermatitis (AD) in developed
      countries has been related to familiar and environmental factors. This survey was
      undertaken to investigate the family background, birthweight and the home
      environment of children suffering from AD in order to point out the possible
      factors that provoke the development of the disease. METHODS: The study uses data
      collected by means of self-administered questionnaires and discusses 461 cases of
      children (age 0-12) with active skin signs of AD. The control group comprised of
      343 children (age 0-12) with no skin signs or positive lifetime history of AD.
      Associations between familiar and various home environmental factors and the risk
      of AD were calculated by means of odds ratios. RESULTS: There were statistically
      significant positive associations between atopic eczema symptoms and higher
      birthweight, small households, wall-to-wall carpets, as well as indoor-kept pets.
      Day-nursery attendance, heating system and indoor smoking, however, did not
      significantly alter the risk of the disease. CONCLUSIONS: Because of the
      limitations of a retrospective questionnaire study, further research is needed to
      confirm these associations and clarify whether they are causative.

PMID- 16643140
TI  - Exercise-induced vasculitis.
AB  - BACKGROUND: Usually misdiagnosed and ignored in the literature, exercise-induced
      vasculitis (EIV) is not uncommon, occurring mostly in long-distance runners and
      in females after long walks, especially in hot weather. OBSERVATIONS: I report 23
      otherwise healthy patients (22 females, 1 male) who developed EIV after walking
      or hiking in hot weather. Erythematous, urticarial or purpuric plaques arose on
      the lower legs, not involving skin compressed by socks. Symptoms included itch,
      pain, and burning sensation. Lesions resolved after some days. Relapses were
      frequent at further muscular exercise, and could be prevented in some cases by
      compression hosiery, manual lymphatic drainage, intake of oedema protective
      agents, or steroids (local or systemic). INVESTIGATIONS: Histopathology
      demonstrated leucocytoclastic vasculitis in five biopsies, and urticarial
      vasculitis in one. Extensive blood investigations have been performed in six
      patients and were negative. No clear relation with chronic venous disease (duplex
      or Doppler) had been established in 12 patients. CONCLUSIONS: I suggest
      denominating this condition exercise-induced vasculitis. This clinical entity is
      well defined, but poorly recognized. The presentation of 23 original cases
      demonstrates its reality.

PMID- 16643141
TI  - Cutaneous plasmacytosis associated with lung and anal carcinomas.
AB  - Cutaneous plasmacytosis is a rare disorder characterized by a benign
      proliferation of mature plasma cells that appears as multiple dark-brown to
      purplish skin lesions, often associated with polyclonal hypergammaglobulinaemia.
      We present the case of a 55-year-old Caucasian man who suffered from a cutaneous
      plasmacytosis associated with two different carcinomas. Cutaneous plasmacytosis
      seems to be a reactive process because most cases reported are not associated
      with any apparent underlying disease. Nevertheless, because few reported cases
      were associated with malignancies, screening of additional neoplasms would be
      justified.

PMID- 16643142
TI  - Metastatic malignant melanoma presenting with hypercalcaemia and bone marrow
      involvement.
AB  - We report a 75-year-old female patient with a background of malignant melanoma
      who presented with hypercalcaemia to our institution. She was aggressively
      treated but declined clinically. Computed tomography head and X-ray studies were
      suggestive of multiple myeloma, but bone marrow examination was significant for
      metastatic malignant melanoma. Very few patients with melanoma present with these
      features, and it further exemplifies the importance of close follow-up and the
      aggressive nature of this disease process.

PMID- 16643143
TI  - Minocycline-induced cutaneous hyperpigmentation: confocal laser scanning
      microscope analysis.
AB  - BACKGROUND: Minocycline has a characteristic yellow-green fluorescent emission.
      This fluorescence has been previously demonstrated only in type 1 minocycline
      induced skin hyperpigmentation. OBJECTIVE: To investigate whether the
      fluorescence can be detected in other types of minocycline-induced cutaneous
      hyperpigmentation, and to study the possible mechanisms. METHODS: Biopsies of
      pigmented and nonpigmented skin from 3 patients with different types of skin
      hyperpigmentation induced by minocycline were analysed by light microscopy and
      Confocal Laser Scanning Microscope (CLSM). RESULTS: A yellow-green fluorescence
      was observed in the hyperpigmented skin of two patients with type 2, and one
      patient with type 4 minocycline-induced cutaneous hyperpigmentation. No
      fluorescence was detected in the non-pigmented skin. CONCLUSION: Minocycline can
      possibly serve as a fluorescent probe in the diagnosis of all types of
      minocycline-induced cutaneous hyperpigmentation.

PMID- 16643144
TI  - Pyoderma gangrenosum as first clinical manifestation of gastric adenocarcinoma.
AB  - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology
      characterized by typical skin ulcers. It may be related to systemic disorders but
      its association with solid tumors is very unusual. In this setting, we describe a
      patient in whom PG was the first and isolated manifestation of advanced gastric
      adenocarcinoma.

PMID- 16643145
TI  - Cutaneous, pulmonary and hepatic sarcoidosis associated with autoimmune
      complications during interferon-alpha treatment for hepatitis C virus infection.
AB  - A patient with hepatitis C virus (HCV) infection was diagnosed with cutaneous,
      pulmonary and hepatic sarcoidosis following interferon alpha therapy. There are
      only a few cases of sarcoidosis associated with this treatment. This is the first
      case who not only developed sarcoidosis, but also autoimmune hypothyroidism and
      thrombocytopenia during interferon alpha therapy due to the immunomodulatory
      effects of the drug.

PMID- 16643146
TI  - Basal cell carcinoma of the vulva.
AB  - Basal cell carcinoma (BCC), the most common human malignancy, accounting for 75%
      of all non-melanoma skin cancer, is uncommon on unexposed skin such as the
      perianal and genital regions. We describe a woman with BCC of the vulva treated
      with local resection. All margins of excision were free of disease. The patient
      recovered without complication and there have been no recurrences after 2 years
      of follow-up. Approximately 200 cases of BCC on perianal and genital skin have
      been reported in the literature. Although the aetiology of vulvar BCC is not
      known, early diagnosis is important. Because BCC in these sites sometimes seems
      innocuous, biopsy of all suspect lesions is advisable.

PMID- 16643147
TI  - Cutaneous Crohn's disease mimicking Melkersson-Rosenthal syndrome: treatment with
      methotrexate.
AB  - A woman with a 5-year history of unilateral orofacial granulomatosis required
      repeated evaluations (including sequential colonoscopies) to establish the
      diagnosis of cutaneous Crohn's disease, a condition that proved responsive to low
      doses of oral methotrexate administered weekly. To our knowledge this is the
      first report describing the use of methotrexate for treatment of orofacial
      granulomatosis caused by underlying Crohn's disease.

PMID- 16643148
TI  - Aleukaemic leukaemia cutis as an initial manifestation of myeloid/NK cell
      precursor acute leukaemia.
AB  - Aleukaemic leukaemia cutis is a rare condition characterized by infiltration of
      leukaemic cells into the skin before they appear in the peripheral blood. We
      report a case of an aleukaemic leukaemia cutis, which had a history of exposure
      to atomic bomb radiation. A 57-year-old Japanese woman initially presented with a
      20-week history of multiple red papules and plaques mainly over the trunk.
      Histological examination revealed the infiltration of atypical monocytic cells in
      the dermis, but no leukaemic cells were detected in the peripheral blood. Twenty
      three weeks after the appearance of the eruption, leukaemic cells were detected
      in the peripheral blood for the first time. The results of immunohistochemistry
      of the skin biopsy specimen and flow cytometry of the peripheral blood indicated
      the rare phenotype of myeloid/NK cell precursor acute leukaemia. This is the
      first case report of myeloid/NK cell precursor acute leukaemia presenting as
      aleukaemic leukaemia cutis in the English literature, and awareness of this
      clinical presentation may be important to reach the correct diagnosis.

PMID- 16643149
TI  - Cutaneous myospherulosis and membranous lipodystrophy: extensive presentation in
      a patient with severe steroid-induced dermal atrophy.
AB  - Myospherulosis is a rare disorder that may develop in various organs including
      the skin. It is characterized by a typical histological presentation resulting
      from the interaction between erythrocytes and lipids. We present a case of
      cutaneous myospherulosis associated with membranous lipodystrophy. The lesions
      were supervening on severe steroid-induced skin atrophy upon which ointments had
      been applied.

PMID- 16643150
TI  - Asymmetric periflexural exanthem of childhood: report of two cases with
      parvovirus B19.

PMID- 16643151
TI  - Subcutaneous granuloma annulare in an adult patient.

PMID- 16643152
TI  - Increased suicidal tendency in a case of psoriasis vulgaris under acitretin
      treatment.

PMID- 16643153
TI  - Atypical molluscum contagiosum.

PMID- 16643154
TI  - Recurrent postoperative pyoderma gangrenosum complicating pacemaker insertion.

PMID- 16643155
TI  - Multiple cutaneous leiomyomas of the nipple.

PMID- 16643156
TI  - Extensive partial unilateral lentiginosis.

PMID- 16643157
TI  - Cutaneous multifocal melanoma metastases clinically resembling herpes zoster.

PMID- 16643158
TI  - Multiple and extensive lichen planus-like keratoses: an underestimated cutaneous
      eruption observed in patients with intense sun damage.

PMID- 16643159
TI  - Grand mal seizure induced by interferon-alpha-2b.

PMID- 16643160
TI  - Prevalence of Demodex folliculorum in young adults: relation with
      sociodemographic/hygienic factors and acne vulgaris.

PMID- 16643161
TI  - Tattoo inoculation lupus vulgaris in two Indian ladies.

PMID- 16643162
TI  - Subcutaneous dirofilariasis caused by Dirofilaria immitis mimicking a large
      epidermal cyst.

PMID- 16643163
TI  - Confluent and reticulated papillomatosis and acanthosis nigricans in an obese
      girl: two distinct pathologies with a common pathogenetic pathway or a unique
      entity dependent on insulin resistance?

PMID- 16643164
TI  - POEMS syndrome characterized by glomeruloid angioma, osteosclerosis and
      multicentric Castleman disease.

PMID- 16643165
TI  - Dermoscopy of molluscum contagiosum: a useful tool for clinical diagnosis in
      adulthood.

PMID- 16643166
TI  - Is inflammatory linear verrucous epidermal naevus a form of linear naevoid
      psoriasis?

PMID- 16643167
TI  - Allergic contact dermatitis from henna temporary tattoo.

PMID- 16643168
TI  - Necrotic arachnidism from Loxosceles rufescens harboured in Crete, Greece.

PMID- 16643169
TI  - Hydroxychloroquine-induced pigmentation in two patients with systemic lupus
      erythematosus.

PMID- 16643170
TI  - Gastroesophageal reflux disease in obese patients: the role of obesity in
      management.
AB  - Gastroesophageal reflux disease (GERD) is common in obese patients. The
      implications of obesity in the etiology, management and outcomes in treatment for
      GERD have become increasingly important due to an epidemic of obesity. The
      increasing prevalence of patients with both obesity and GERD merits evaluation of
      the appropriate surgical intervention for GERD and its symptoms. With the
      additional advantages of weight loss and resolution of weight-related morbidity
      (including GERD) bariatric procedures should be the procedure of choice in
      patients with medically complicated obesity. Patients in lower obesity classes
      with body mass indices (BMI) of 30-35 kg/m2 without other substantive weight
      related comorbidity should prompt consideration of both fundoplication and
      bariatric procedures, tailoring the best approach based on the specific patient
      and future implications. Patients classified as overweight but not obese (BMI <
      30) are likely best treated with fundoplication; however, no randomized trials
      comparing fundoplication with the current antireflux bariatric procedures exist.

PMID- 16643171
TI  - Detection of human papillomavirus DNA in squamous cell carcinoma of the esophagus
      by auto-nested PCR.
AB  - The aim of the present study was to investigate the presence of human
      papillomavirus (HPV) in surgical specimens of esophageal squamous cell carcinoma.
      One hundred and sixty-five paraffin-embedded specimens of esophageal carcinoma
      were analyzed through high-sensitivity auto-nested polymerase chain reaction
      (PCR) using the consensus GP5+/GP6+ primer. Twenty-six specimens of esophageal
      mucosa without malignant disease were also studied as a control group. Two
      different specific primer sets targeting the E6 region of the HPVs 16 and 18 were
      used for typing. Direct DNA sequence analysis was conducted to confirm positive
      PCR results. HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in
      none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases,
      24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA.
      Positive PCR results were confirmed by the amplified viral sequences. Our
      findings suggest that the presence of either HPV-16 or -18 might be related to
      development of the malignant phenotype in the esophagus.

PMID- 16643172
TI  - Survival outcomes of resected patients who demonstrate a pathologic complete
      response after neoadjuvant chemoradiation therapy for locally advanced esophageal
      cancer.
AB  - A variety of strategies, using chemotherapy, radiation therapy, and surgical
      resection have been employed in the treatment of locally advanced esophageal
      cancer. No strategy has proven superior, and poor long-term survival is
      anticipated. A survival benefit has been suggested for patients who achieve a
      pathologic complete response (pCR) following neoadjuvant chemoradiation therapy.
      We examined the collective results at three institutions of patients who achieved
      a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based
      review was conducted. Kaplan-Meier calculations were used to determine overall
      and disease-free survival. Between 1995 and 2002, 229 patients were treated with
      neoadjuvant chemoradiation followed by surgery as a planned approach for locally
      advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were
      the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and
      adenosquamous/undifferentiated in two patients. Forty patients were staged by
      endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage
      of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in
      the perioperative period. The remaining patients have been followed for an
      average of 46 months. Overall survival at 5 years was 56.4% and a median survival
      has not been reached. Esophageal cancer patients who demonstrate a pCR following
      neoadjuvant chemoradiation are a select subset who demonstrate excellent long
      term survival. Identification of clinical variables or biomarkers predictive of
      pCR may therefore optimize treatment strategies of patients with locally advanced
      esophageal cancer.

PMID- 16643173
TI  - Prognosis of patients who develop cervical lymph node recurrence following
      curative resection for thoracic esophageal cancer.
AB  - Patients with esophageal cancer often display relapse at cervical nodes after
      surgery, but their prognosis and a suitable therapy remains unknown. We
      retrospectively reviewed the records for 35 patients who underwent esophagectomy
      with lymphadenectomy who then displayed relapse at the cervical lymph nodes alone
      between 1985 and 2003 in order to observe the prognostic factors for such
      patients. Median survival time from the date of recurrence for all 35 patients
      was 12 months with 1-year, 2-year, 3-year and 5-year survival rate of 47.2%,
      26.5%, 17.7% and 8.8%, respectively. With regard to the initial treatment against
      cervical node recurrence, 15 patients were treated by radiotherapy alone, eight
      by chemoradiotherapy, 11 by surgery and one by chemotherapy alone. Univariate
      analysis revealed that cervical node dissection at the prior esophagectomy
      (yes/no, P = 0.0178), time to recurrence (> 9 months or < 9 months, P = 0.0497)
      and the number of relapsed nodes (solitary/multiple, P = 0.0029) were significant
      prognostic factors. Among these factors, the number of relapsed nodes
      (solitary/multiple) was found to be the only significant prognostic factor with
      an odds ratio of 2.409 and 95% confidence interval of 1.033-5.619 by multivariate
      analysis. In conclusion, cervical node metastasis is generally considered to be
      distant organ metastasis. However, if it is a solitary node recurrence,
      substantial survival can be attained by appropriate loco-regional therapy.

PMID- 16643174
TI  - Management of locoregional stage esophageal cancer: a single center experience.
AB  - Therapeutic options for locoregional esophageal cancer (EC) include primary
      surgery, neoadjuvant or definitive chemoradiation and systemic chemotherapy. The
      role of surgery in these multimodal strategies has recently been debated and
      definitive chemoradiation is being offered as an alternative to surgery at many
      centers. We examined our results with multimodal therapy and surgery in this
      patient population. We conducted a retrospective analysis of 172 patients with
      locoregional (AJCC stages I-III) EC treated at RPCI between February 14, 1990 and
      September 20, 2002. Median age was 65 years (range, 36-95); there were 136 male
      patients. There were 100 regional (stages IIB-III), 69 local (stages I-IIA) and
      three in situ cases. Initial therapy was either combined modality (n = 122) or
      single modality (surgery) (n = 50). There was 0%, 30-day, postoperative
      mortality. Median survival for all patients was 25.3 months and was better for
      local stage with surgery alone (75 months) than with neoadjuvant (35.7 months) or
      definitive chemoradiation (19.1 months, P < 0.001). Survival for patients with
      regional disease treated with surgery alone, neoadjuvant or definitive
      chemoradiation was 21.5, 24.4 and 11.8 months, respectively (P = not
      significant). The associations of prognostic factors with overall survival were
      evaluated using Cox proportional hazards regression analysis and 2-sided Wald's
      chi-square test. On multivariate analysis, carefully selected patients treated
      with surgery alone had better outcomes compared with those treated with
      definitive chemoradiation (P < 0.001). Patients with locoregional esophageal
      cancer who are eligible for surgical resection either alone or as a part of
      multimodal therapy may have better outcomes than those treated with non-surgical
      approaches.

PMID- 16643175
TI  - Barrett's esophagus specialist clinic: what difference can it make?
AB  - A 'Barrett's specialist clinic' was set up in our institution consisting of a
      specialist nurse, research fellow, and a consultant gastroenterologist. The aim
      of our study was to examine the impact of this clinic in the management of
      patients with Barrett's esophagus (BE). Patients with the diagnosis of BE seen in
      the outpatient departments or in the endoscopy unit were referred to this clinic.
      Guidelines were introduced modelling the American College of Gastroenterology
      recommendation. Patients were assessed based on their comorbidity and willingness
      to undergo surveillance. Reflux symptom control and acid suppression was
      addressed. All patients were invited to undergo high-resolution enhanced
      magnification endoscopy (EME) and targeted biopsy to confirm the diagnosis and to
      form a management plan. During the appointment in the clinic, patients were given
      an option to fill a questionnaire that inquired about the information given to
      them regarding BE. One hundred and forty-three patients (92 men, mean age: 62
      years) with a diagnosis of BE were seen in the specialist clinic. In 16 patients
      surveillance was stopped. In 25 patients treatment was changed due to poor
      control of reflux symptoms. Sixty-five patients (51%) answered the questionnaire.
      Seventy-five patients (58%) underwent high resolution EME. Twelve patients, had a
      histological upgrade after EME, in spite of a short mean screening interval (5.5
      months). The 'Barrett's specialist clinic' introduced a more structured approach
      in our institution and changed the way these patients were managed. Our results
      indicate the need for local guidelines and Barrett's specialist clinics in the
      UK, and perhaps in the rest of the Western world, wherein the burden of this
      condition is increasing.

PMID- 16643176
TI  - Qualitative analysis of the expectations of antireflux surgical outcomes of
      patients from different nationalities.
AB  - Patient-reported outcomes have grown in importance in assessing the value of a
      variety of treatments. One of the methods of assessing patient-reported outcomes
      is qualitative analysis. The purpose of this study was to assess if qualitative
      analysis can be used to assess patient expectations for antireflux surgery in
      different nationalities. Patients referred for antireflux surgery (ARS) in the
      US, Austria and Italy were prospectively studied. Preoperatively, they were
      asked: (i) 'How do you expect the surgery to affect your symptoms?'; (ii) 'What
      do you expect the possible complications or side effects to be?' These patients
      then underwent open or laparoscopic antireflux surgery. At 2-3 months
      postoperatively, they were asked: (i) 'Are you satisfied with your surgery? If
      so, why? If not, why not?'; (ii) 'Did your surgery meet your expectations? If
      not, why not?' Twenty patients in the US, 24 in Austria, and 18 in Italy
      completed the study. Preoperatively, there were significant differences between
      the patients in demographics and objective measurements of GERD. Symptomatic
      relief was the most common expectation. There was variation in question #2, with
      Austrian and Italian patients more likely to mention conversion and postoperative
      side effects. Postoperatively, 90% of American, 88% of Austrian, and 89% of
      Italian patients were satisfied. Causes for dissatisfaction were postoperative
      complications, symptomatic recurrences, or side effects. Ninety percent of
      American, 96% of Austrian, and 94% of Italian patients said that their
      expectations were met. Patients who did not mention the possibility of side
      effects or complications were more likely to be dissatisfied. Qualitative
      analysis is a useful tool in assessing patient expectations. Expectations were
      remarkably similar. Patients who did not mention postoperative adverse events as
      possibilities preoperatively were more likely to be dissatisfied.

PMID- 16643177
TI  - Laparoscopic fundoplication in patients with an aperistaltic esophagus and
      gastroesophageal reflux.
AB  - A minority of patients with severe gastroesophageal reflux who present to
      surgeons for antireflux surgery have absent esophageal peristalsis when
      investigated before surgery with esophageal manometry. Some of these patients
      also have systemic sclerodema. While conventional wisdom suggests that these
      patients are at risk of a poor outcome if they proceed to fundoplication, some
      will have severe reflux symptoms, which are poorly controlled by medical therapy,
      and surgery will therefore offer the only chance of 'cure'. We performed this
      study to determine the outcome of laparoscopic fundoplication in the subset of
      patients with gastroesophageal reflux and an aperistaltic esophagus. From 1991 to
      2003, the operative and follow-up details for all 1443 patients who underwent a
      laparoscopic fundoplication in our Departments have been prospectively collected
      on a database. These patients were then followed yearly using a standardized
      symptom assessment questionnaire. A subset of patients whose preoperative
      esophageal manometry demonstrated complete absence of esophageal body peristalsis
      and absent lower esophageal sphincter tone (aperistaltic esophagus) were
      identified from this database, and their outcome following laparoscopic
      fundoplication was determined. Twenty-six patients with an aperistaltic esophagus
      who underwent a laparoscopic fundoplication were identified. Six of these had a
      systemic connective tissue disease (scleroderma), and 20 had an aperistaltic
      esophagus without a systemic disorder. A Nissen fundoplication was performed in
      four patients, and an anterior partial fundoplication in 22. Follow-up extended
      up to 12 years (median, 6). A good overall symptomatic outcome was achieved in
      88% at 1 year, 83% at 2 years and 93% at 5-12 years follow-up. Reflux symptoms
      were well controlled by surgery alone in 79% at 1 year, and 79% at 5-12 years. At
      2 years, 87% were eating a normal diet. Two patients underwent further surgery -
      one at 1 week postoperatively for a tight esophageal hiatus, and one at 1 year
      for recurrent reflux. Patients with troublesome reflux and an aperistaltic
      esophagus can be effectively treated by laparoscopic fundoplication. An
      acceptable outcome will be achieved in the majority of patients.

PMID- 16643178
TI  - Free radical production in the esophago-gastro-duodenal mucosa in response to
      acid and bile.
AB  - Several studies have demonstrated the role of free radicals in causing esophagus
      gastro-duodenal mucosal injury. The present study has been designed to
      investigate: whether acid, bile salts and a combination of bile + acid could
      determine the production of O2-derived free radicals by oesophageal, gastric and
      duodenal mucosa; which agent is capable of producing more free radicals and if O2
      derived free radicals production depends on the duration of contact with acid,
      bile salts and their combination. Wistar rats' gastro-intestinal mucosa were
      perfused with bile, acid and a combination of bile + acid at pH4 and pH2 for 1
      hour and 2 hours. Free radical production (FRP) was assessed by
      chemoluminescence. After 1 hour, the increase in FRP in comparison with control
      reached statistical significance (P < 0.05) at all tested pH levels in the
      duodenum, at pH1, 2 and 3 in the esophagus, and at pH1 in the stomach. Comparing
      different segments, both the esophagus and duodenum behaved similarly, producing
      more free radicals than the stomach at all pH values. However, this difference
      reached statistical significance at pH1 and 2 only. In comparison to control, FRP
      was increased by bile (pH7) infusion after 1 and 2 hours. There was increased FRP
      in all segments after the infusion of bile at pH2 and 4 in comparison to control.
      Infusion of bile at pH2 stimulates more FRP than infusion of bile at pH4 in all
      segments. This increased FRP reaches statistical significance in the esophagus
      after 2 hours of infusion, in the stomach after 1 and 2 hours of infusion, but in
      the duodenum it does not reach statistical significance. Acid, bile and bile +
      acid at pH2 and 4 can cause free radical production in esophageal, gastric and
      duodenal mucosa. Their role in producing free radicals is different according to
      the segment and the chemical composition of the solution.

PMID- 16643179
TI  - Black esophagus: report of six cases and review of the literature, 1963-2003.
AB  - Black esophagus is the uncommon endoscopic finding of extensive black
      discoloration of the esophageal mucosa, usually from acute esophageal necrosis.
      Six cases of black esophagus were seen at Mayo Clinic (Rochester, Minnesota, USA)
      from 1997 through 2003, and 46 cases were reported in the English-language
      literature from 1963 through 2003. We studied the demographics, clinical
      features, and outcomes of these 52 cases of black esophagus. Age and sex were
      known for 50 patients: the mean (SD) age was 65 years (19), and 42 patients (84%)
      were men. Symptoms were known for 51 patients: the most common symptom was upper
      gastrointestinal tract bleeding, occurring in 40 patients (78%). All 52 patients
      had at least one comorbid condition (with most having two or more), including
      duodenal ulcer in 17 (33%), cancer in 15 (29%), renal insufficiency in 15 (29%),
      and diabetes mellitus in 14 (28%). The suspected cause of black esophagus was
      reported for 40 patients: ischemia in 22 (55%); massive gastroesophageal reflux
      in seven (18%); and esophageal infection (Lactobacillus acidophilus, herpes
      simplex, Candida albicans) in four (10%). Most patients received supportive
      therapy, particularly acid suppression therapy. Of the 47 patients for whom
      outcomes were known, 17 (36%) died. There were no statistically significant
      differences between survivors and non-survivors. Black esophagus typically occurs
      in older men with at least one comorbid condition; a substantial number of
      patients die. Although the underlying mechanism leading to black esophagus is
      unknown, clinicians caring for patients with black esophagus should focus on
      optimizing perfusion, minimizing acid reflux, and treating esophageal infection
      if present.

PMID- 16643180
TI  - Sub-diaphragmatic fascia: role in the recurrence of hiatal hernias.
AB  - One of the most common causes of a failed Nissen fundoplication is disruption of
      the crural repair. We investigated the thickness of the subdiaphragmatic fascia
      overlying the right and left limb of the right crus in cadavers to determine any
      difference. Sub-diaphragmatic fascia specimens were obtained from three sites
      adjacent to the hiatus in 20 preserved cadavers. One square centimeter of fascia
      was excised 3 cm from the arch of the hiatus on each side and approximately 2-3
      mm from the edge of the hiatal opening (labeled RL and LPL). A third sample was
      taken 1 cm from the arch of the hiatus on the left side (labeled LAL). The
      thickness of these tissues was measured. The mean tissue thickness of RL, LPL and
      LAL were 0.22 mm, 0.23 mm and 0.4 mm, respectively. There was no difference in
      tissue thickness between the lower specimens on both sides (RL vs. LPL); however,
      LAL was significantly thicker than both RL and LPL (P < 0.05). The thickness of
      the subdiaphragmatic fascia overlying the right and left limb of the right crus
      does not differ significantly in the region used for crus closure during
      antireflux surgery; however, the fascia on the left is thicker anteriorly.

PMID- 16643181
TI  - Surgical repair of redundant intra-thoracic stomach after Ivor Lewis
      esophagectomy.
AB  - We present two patients with low esophagogastric anastomosis, redundant
      intrathoracic stomach, and markedly symptomatic reflux and regurgitation after
      Ivor Lewis esophagectomy. The diagnosis, technique of surgical revision, and
      outcome is discussed.

PMID- 16643182
TI  - Esophageal carcinosarcoma with intramural metastasis.
AB  - A case of esophageal carcinosarcoma is described herein. A 58-year-old man
      presented with dysphagia and was admitted to our hospital. Imaging studies
      revealed a type 3 tumor in the upper intrathoracic esophagus with direct invasion
      to the left main bronchus. Analysis of a biopsy specimen revealed carcinosarcoma.
      The patient underwent esophageal bypass and chemoradiotherapy. Eight months after
      surgery, he died of esophago-bronchial fistula. Autopsy examination revealed
      liver metastasis, peritoneal dissemination and intramural metastasis. The
      sarcomatous component was predominant in the intramural and liver metastatic
      lesions.

PMID- 16643183
TI  - Thoracoscopic resection of esophageal duplication cysts.
AB  - Esophageal duplication is a rare congenital esophageal disorder. Surgical
      excision is the standard treatment for symptomatic esophageal duplication cysts.
      Traditionally, the resection is accomplished via thoracotomy; however, a
      minimally invasive approach is possible, avoiding the long hospital stay, the
      discomfort and the long recovery time due to a thoracotomy. The authors describe
      two cases of esophageal duplication resected via a left thoracoscopic approach.

PMID- 16643186
TI  - Trends in incidence and survival of mesenchymal neoplasm of the digestive tract
      within a defined population of northern Norway.
AB  - Population-based incidence and survival data for gastrointestinal stromal tumor
      (GIST) are sparse due to the fact that GIST is a rather novel entity both
      clinically and pathologically, and has not been registered as a separate entity
      in population-based cancer registries. The aim of the present study was to
      reclassify all mesenchymal tumors within a defined population of northern Norway
      over a time-span of 30 years with the purpose of estimating trends of incidence
      and survival. One hundred and forty-one patients with mesenchymal neoplasms of
      the digestive tract were identified: 102 as GISTs, 32 as leiomyomatous tumors, 4
      as schwannomas, and 3 as fibromas. Incidence rates of GIST showed a significant
      increase over the whole period, which was not observed for the non-GIST cases.
      Analysis of GIST cases showed that cases with more than 5 mitoses per 50 high
      power fields had an increased expected mortality 4 times that of those with fewer
      mitoses, and the combination of mitotic count and size of tumor can be
      recommended for categorizing the tumors into different risk levels. The study
      confirms that GIST is by far the most frequent mesenchymal neoplasm of the
      digestive tract and that the incidence has increased over the last 30 years.

PMID- 16643187
TI  - Tumour regression and mesorectal lymph node changes after intensified neoadjuvant
      chemoradiation for carcinoma of the rectum.
AB  - Neoadjuvant radiation or chemoradiation is currently the treatment of choice for
      patients with locally advanced carcinoma of the rectum. To assess the effects of
      chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a
      consecutive series of 76 patients receiving neoadjuvant chemoradiation and a
      stage-adapted control series of 57 patients without pretreatment were studied.
      Densities of cells positive for CD4 (T-helper cells), CD8 (cytotoxic T-cells),
      CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on
      immunostains. Tumour regression was graded, and presence or absence of extramural
      tumour was recorded. The densities of CD4+ T-lymphocytes and CD83+ dendritic
      cells in the paracortex of mesorectal lymph nodes were observed to be
      significantly reduced, as were the densities of CD57+ cells in the follicles;
      densities of CD8+ T-lymphocytes did not differ. Strong, moderate and poor tumour
      regression was observed in 29, 25, and 22 cases, respectively. For 12 patients,
      absence of extramural vital or regressing tumour was recorded, indicating
      pretherapeutic overstaging. The results bring to mind that neoadjuvant
      chemoradiation as a side effect may have a negative impact on anti-tumour
      immunity. Together with the drawback of overstaging the results argue for a
      careful selection of patients.

PMID- 16643188
TI  - Influence of angiogenesis inhibitors on endothelial cell morphology in vitro.
AB  - Human umbilical vein endothelial cells (HUVEC) propagated in co-culture with
      fibroblasts form capillary-like networks of tubes. Here we characterize the
      morphology and ultrastructure of HUVEC in such co-cultures and investigate the
      influence of different angiogenesis inhibitors on endothelial cell morphology.
      Addition of angiogenesis inhibitors to the co-culture disrupted endothelial
      network formation and influenced endothelial cell morphology in two distinct
      ways. Instead of characteristic capillary-like networks, the endothelial cell
      morphology appeared as either short cords or compact cell clusters of variable
      size. Electron microscopy (EM) showed that in co-culture untreated HUVEC formed
      capillary-like tubes with lumina and retained important ultrastructural and
      physiological properties of endothelial cells in functional vessels as they
      contained both Weibel-Palade bodies and transport vesicles. Immuno-EM showed that
      the endothelial cell marker CD 31 stained endothelial membranes at cell-cell
      contacts, and at the luminal and abluminal side of the capillary-like tubes,
      although most abundantly at the luminal membranes. No ultrastructural signs of
      apoptosis were seen in HUVEC in inhibitor-treated co-cultures. Our results
      demonstrate that treatment with levamisole or anti-VEGF inhibits endothelial cell
      differentiation into tubes or instead induces formation of compact endothelial
      cell clusters. Treatment with platelet factor 4, suramin and TNP-470 results in
      formation of short endothelial cell cords. We discuss the implications of these
      findings.

PMID- 16643189
TI  - Tyrosine kinase inhibitors alter adhesivity of prostatic cancer cells to
      extracellular matrix components.
AB  - Tyrosine kinase inhibitors (TKIs) are thought to have potential as a new
      generation of anti-cancer drugs. Since invasiveness, the main characteristic of
      malignant behaviour, is believed to depend on altered cell-matrix interactions,
      we investigated the effect of two potent TKIs, genistein and tyrphostin AG-1478,
      on the interaction of prostate cancer cells with extracellular matrix components.
      PC-3 and DU-145 cells were treated with various concentrations of genistein and
      tyrphostin AG-1478. Adhesion to extracellular matrix was assayed using
      fluorescence-labelled cells seeded on collagen type I, collagen type IV,
      fibronectin, laminin and vitronectin. The expression levels of integrin beta1,
      alpha2, alpha3 and alpha5 subunits were measured using flow cytometry of cells
      labelled with monoclonal murine antibodies. Genistein treatment reduced the
      ability of both cell lines to adhere to the matrix proteins tested. This effect
      was more pronounced for PC-3 cells than for DU-145 cells. Genistein treatment
      decreased the expression of beta1 integrins by 40% in PC-3 cells and 22% in DU
      145. AG-1478 treatment slightly reduced the ability of DU-145 cells to adhere,
      but did not decrease PC-3 cell adhesion. Nevertheless, expression levels were
      reduced for most integrins tested, except the expression of alpha-5, for which no
      significant effect was measured. Our results point to a possible role of TKIs as
      suppressors of prostate carcinoma cell adhesion to extracellular matrix
      components, by acting as inhibitors of integrin expression.

PMID- 16643190
TI  - Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma
      component and leiomyosarcomatous and myofibroblastic differentiation as the
      sarcomatous component.
AB  - Gastric carcinosarcoma with neuroendocrine differentiation is a very rare
      neoplasm. In this article we present such a case. The gastroendoscopic
      examination of a 59-year-old Japanese man disclosed gastric cancer during follow
      up after operation for rectal cancer. Subsequently, total gastrectomy was carried
      out because of gastric cancer. A large tumor measuring 9.2 x 8.4 cm was observed
      in the posterior wall of the upper portion of the stomach. The tumor was composed
      of carcinoma and sarcomatous cells, and the histological transition of both
      components was observed. Immunohistochemically, carcinoma and sarcomatous cells
      were positive for cytokeratin CAM5.2. The carcinoma contained adenocarcinoma and
      malignant cells with neuroendocrine differentiation. The sarcomatous component
      showed leiomyosarcomatous and myofibroblastic differentiation. The present tumor
      is the fifth case of gastric carcinosarcoma with neuroendocrine differentiation
      and the first case of gastric carcinosarcoma with myofibroblastic
      differentiation. Pathologists should bear in mind that gastric carcinosarcoma may
      show various types of differentiation.

PMID- 16643191
TI  - Is it really important for sick people to perform exercise?

PMID- 16643192
TI  - Structural and functional features of human muscle-tendon unit.
AB  - This paper reviews the architectural details and the in vivo behavior of the
      human muscle-tendon unit with the focus on the triceps surae and quadriceps
      femoris muscles. Recent advances in experimental techniques allow in vivo
      measurements of muscle-tendon architecture and function. In particular, the use
      of ultrasonography for measurement of tendon and muscle has expanded our
      knowledge in the last decade. Furthermore, the nuclear magnetic resonance imaging
      is opening up new insights not only for three-dimensional anatomical information
      but also for examining musculo-skeletal motion in vivo. While these two
      completely non-invasive methods provide kinematic data, in vivo force
      measurements still require somewhat invasive procedures and are scarce. Thus,
      muscle forces are frequently calculated using both simple and complex models.
      These models can give us suggestions for further experimental work. There is a
      need to examine the experimental data ranging from single-fiber experiments to
      the muscle function in human movement in order to understand the muscle-tendon
      function in vivo fully. Furthermore, appreciation of the structure-function
      relationships may help us to understand the entity of muscle-tendon function both
      from the perspective of mechanical behavior and neural control.

PMID- 16643193
TI  - Effects of isometric training at different knee angles on the muscle-tendon
      complex in vivo.
AB  - The purpose of this study was to investigate the influences of isometric training
      at different joint angles on the muscle size and function of the human muscle
      tendon complex in vivo. Furthermore, we tried to gain a better understanding of
      the mechanisms involved in angle specificity after isometric training from the
      aspect of neuromuscular adaptation and the changes in the properties of the
      muscle-tendon complex. Nine males completed 12-week unilateral training program
      (70% of maximal voluntary contraction (MVC) x 15 s x six sets) on the knee
      extensors at 50 degrees (shorter muscle length: ST) and 100 degrees (longer
      muscle length: LT). The internal muscle force (mechanical stress) is higher at
      100 degrees than at 50 degrees because of the difference in the moment arm
      length, although there were no difference in the relative torque level,
      contraction and relaxation times, and repetition between ST and LT. Before and
      after training, isometric strength at eight angles and muscle volume were
      determined. Tendon elongation of knee extensors was measured by ultrasonography.
      There was no significant difference in the rate of increment of muscle volume
      between the protocols. Tendon stiffness increased significantly for LT, but not
      for ST. Although significant gain was limited to angles at or near the training
      angle for ST, increases in MVC at all angles were found for LT. These results
      suggest that only mechanical stress (internal muscle force imposed on muscle and
      tendon) contributes to adaptation in the tendon stiffness, although metabolic
      (relative torque level, etc.) and mechanical stress relate to muscle hypertrophy.
      Furthermore, increment of tendon stiffness for LT might contribute to increase
      torque output at smaller angles other than the training angle.

PMID- 16643194
TI  - Shoulder pain -- a common problem in world-class badminton players.
AB  - Badminton is a sport that requires a lot of over-shoulder motion, with the
      shoulder in abduction/external rotation. This questionnaire study on 188
      international top-level badminton players during the World Mixed Team
      Championships showed that previous or present shoulder pain on the dominant side
      was reported by 52% of the players. Previous shoulder pain was reported by 37% of
      the players and on-going shoulder pain by 20% of the players. There were no
      significant differences in the prevalence of shoulder pain between men and women.
      The majority of the shoulder pain had started gradually. The pain was usually
      associated with shoulder activity, and stiffness was a common, associated
      symptom. Furthermore, the shoulder pain was associated with consequences such as
      sleeping disturbances, changes in training and competition habits, and it also
      affected activities of daily living. The majority of the players had sought
      medical advice and had been given different kinds of treatment. The study showed
      that shoulder pain is a common and significant problem in world-class badminton
      players, and the consequences are most likely of importance for their training
      and playing capacity.

PMID- 16643195
TI  - Shoulder terminal range eccentric antagonist/concentric agonist strength ratios
      in overhead athletes.
AB  - OBJECTIVE: The agonist-antagonist strength relationship for shoulder external
      rotation and internal rotation was formerly described by the relatively more
      functional ratios of eccentric external rotator to concentric internal rotator
      moments, and eccentric internal rotator to concentric external rotator moments
      for the entire range of motion. The aim of this study was to provide descriptive
      data for terminal range eccentric antagonist/concentric agonist rotator cuff
      strength in overhead athletes. METHOD: The dominant and non-dominant shoulders of
      40 asymptomatic military overhead athletes were tested through a range of 20
      degrees of external rotation to 90 degrees of internal rotation using the Cybex
      NORM isokinetic dynamometer at a speed of 90 degrees /s. Differences between the
      dominant and non-dominant shoulders were assessed using the paired samples t
      test. RESULTS: The terminal range ratios during external rotation (20 degrees of
      internal rotation - 10 degrees of external rotation) were found to be 2.09 and
      1.58 for the dominant and non-dominant shoulders, respectively, whereas the
      terminal range ratios during internal rotation (60-90 degrees of internal
      rotation) were 1.03 and 1.19 for the dominant and non-dominant shoulders,
      respectively. These ratio differences between the dominant and non-dominant
      shoulders were significant (P<0.01 for external and internal rotation).
      CONCLUSION: The muscle torque ratios of eccentric antagonist/concentric agonist
      are different between dominant and non-dominant shoulders of skilled overhead
      athletes at terminal ranges. This functional assessment of strength testing that
      reflects dynamic shoulder joint stability during the throwing activity at these
      specific ranges may provide valuable information either during preventive
      exercise programs or in the evaluation of the injured shoulder of the overhead
      athlete. We recommended functional exercises that improve eccentric external
      rotation strength on the dominant shoulder during the rehabilitation and
      prevention programs in overhead athletes.

PMID- 16643196
TI  - A new instrument for measuring self-efficacy in patients with an anterior
      cruciate ligament injury.
AB  - It has been suggested that self-efficacy belief is of major importance for
      rehabilitation outcome after sports-related injuries. No instruments are,
      however, available to evaluate perceived self-efficacy for prognostic and outcome
      expectations in patients with an anterior cruciate ligament (ACL) injury.
      Perceived self-efficacy is defined as a judgment of one's potential ability to
      carry out a task, rather than a measure of whether or not one actually can or
      does perform the task. The purpose of this study was to develop a reliable and
      valid instrument for measuring perceived self-efficacy in patients with an ACL
      injury. A total of 210 male and female patients with an ACL injury were included
      in this study. The items were generated by health professionals with long
      clinical experience of patients with an ACL injury and by discussions with
      patients. After item analysis and item reduction, based on the results from 88
      patients, the final 22-item version of the Knee Self-Efficacy Scale (K-SES) was
      evaluated in 18 patients for test-retest reliability and in 104 patients for
      internal consistency and validity. The K-SES was compared with the
      Multidimensional Health Locus of Control (MHLC), Coping Strategies Questionnaire
      (CSQ), SF-36 and Knee Injury and Osteoarthritis Outcome Score (KOOS) instruments.
      A factor analysis was also performed on the K-SES. The test-retest revealed a
      correlation of r(s)=0.73 between test-days and an intraclass correlation
      coefficient of 0.75. No significant difference between test-days was found. The
      internal consistency was 0.94, as calculated with Cronbach's alpha. There were
      low correlations between the K-SES and MHLC and the K-SES and CSQ, respectively.
      A strong correlation was found between the K-SES and physical functioning, as
      measured by the SF-36 (r(s)=0.8). All the sub-scales in the KOOS correlated
      moderately to strongly (r(s)=0.4-0.7) to the K-SES. The factor analysis produced
      two factors of importance. Factor one was related to how patients perceived their
      present physical performance/function, while factor two was related to how
      patients perceived the future physical performance/prognosis of their knee. Good
      reliability and good face, content, construct and convergent validity were
      demonstrated for this new instrument (K-SES) for measuring perceived self
      efficacy in patients with an ACL injury. The K-SES is recommended for studies
      designed to evaluate prognostic and outcome expectations of perceived self
      efficacy in patients with an ACL-insufficient knee.

PMID- 16643197
TI  - Exercise-induced rib stress fractures: potential risk factors related to thoracic
      muscle co-contraction and movement pattern.
AB  - The etiology of exercise-induced rib stress fractures (RSFs) in elite rowers is
      unclear. The purpose of the study was to investigate thoracic muscle activity,
      movement patterns and muscle strength in elite rowers. Electromyographic (EMG)
      and 2-D video analysis were performed during ergometer rowing, and isokinetic
      muscle strength was measured in seven national team rowers with a history of RSF
      and seven matched controls (C). RSF displayed a higher velocity of the seat in
      the initial drive phase (RSF: 0.25+/-0.03, 0.25 (0.15-0.33) m/s vs C: 0.15+/
      0.06, 0.18 (-0.11-0.29) m/s P=0.028) (Mean+/-SEM, median and range). Further, RSF
      had greater co-contraction of m. serratus anterior and m. trapezius in the mid
      drive phase (RSF: 47.5+/-3.4, 48.5 (35.8-60.2)% EMG signal overlap vs C: 30.8+/
      6.5, 27.0 (11.2-61.6)%P=0.043). In addition, the RSF subjects showed a lower knee
      extension to elbow-flexion strength ratio (RSF: 4.2+/-0.22, 4.3 (3.5-5.1) vs C:
      4.8+/-0.16, 5.0 (4.2-5.3) P=0.043), indicating stronger arms relative to legs
      compared with controls. In conclusion, increased thoracic muscle co-contraction,
      altered movement patterns and reduced leg/arm strength ratio were observed in the
      RSF subjects, which may all predispose toward an increased risk of RSF.

PMID- 16643198
TI  - Nerve conduction study of ulnar nerve in volleyball players.
AB  - Ulnar neuropathy at the elbow is a common disorder seen in the throwing athlete.
      The purpose of our study was to determine whether asymptomatic physically active
      volleyball players and non-actives demonstrate distinct differences in nerve
      conduction of the ulnar nerve at the elbow. Nerve conduction studies were
      performed on both arms of 24 male volleyball players and 24 male non-actives.
      Nerve conduction velocity at the above to below elbow segment of the ulnar motor
      nerve were slower in the volleyball players compared with controls and their non
      dominant arms. There were no statistical differences in latencies and conduction
      velocity of the ulnar nerve on the forearm, both in volleyball players and in the
      controls. In the evoked responses of the ulnar nerve, the amplitude was the same
      as corresponding normal values in both sensory nerve and muscle action
      potentials. We conclude that abnormal ulnar (motor) nerve conduction at the elbow
      segment may suggest a subclinical entrapment neuropathy as a result of strenuous
      elbow movements in volleyball players.

PMID- 16643199
TI  - Stability and prediction of physical activity in 5-, 10-, and 28-year follow-up
      studies among industrial employees.
AB  - The aim of the study was to examine the stability of voluntary and household
      physical activity (PA) and to compare it with that of the use of the most common
      stimulants. The prospective cohort study comprised of follow-ups at 5, 10, and 28
      years at baseline in 1973 in four plants of an industrial corporation in Finland.
      A systematic, non-proportional sample (n=902, age range 18-64 years) stratified
      for age, gender, and occupational status was drawn from the employees. Scores of
      PA were based on a questionnaire and interviews. Logistic regression models with
      proportional odds assumptions were counted. The 5-year stability (Spearman's rho)
      of PA time was 0.44 (PA intensity 0.44), the respective 10-year coefficient was
      0.26 (0.32), and that in the 28-year follow-up was 0.18 (0.20). The stability of
      PA decreased rapidly from 1973 to 1983 and more slowly thereafter. Changes along
      the follow-up reflect a polarization of the distributions of PA within the
      sample. Age and an initially low level of activity were the strongest predictors
      of inactivity. The stability coefficient of smoking and alcohol consumption was
      twice as high as that of PA. Stimulant use was a greater factor in the
      individual's lifestyle than PA.

PMID- 16643200
TI  - Whole-body fat oxidation determined by graded exercise and indirect calorimetry:
      a role for muscle oxidative capacity?
AB  - During whole-body exercise, peak fat oxidation occurs at a moderate intensity.
      This study investigated whole-body peak fat oxidation in untrained and trained
      subjects, and the presence of a relation between skeletal muscle oxidative enzyme
      activity and whole-body peak fat oxidation. Healthy male subjects were recruited
      and categorized into an untrained (N=8, VO(2max) 3.5+/-0.1 L/min) and a trained
      (N=8, VO(2max) 4.6+/-0.2 L/min) group. Subjects performed a graded exercise test
      commencing at 60 W for 8 min followed by 35 W increments every 3 min. On a
      separate day, muscle biopsies were obtained from vastus lateralis and a 3 h
      bicycle exercise test was performed at 58% of VO(2max). Whole-body fat oxidation
      was calculated during prolonged and graded exercise from the respiratory exchange
      ratio using standard indirect calorimetry equations. Based on the graded exercise
      test, whole-body peak fat oxidation was determined. The body composition was
      determined by DEXA. Whole-body peak fat oxidation (250+/-25 and 462+/-33 mg/min)
      was higher (P<0.05) and occurred at a higher (P<0.05) relative workload (43.5+/
      1.8% and 49.9+/-1.2% VO(2max)) in trained compared with untrained subjects,
      respectively. Muscle citrate synthase activity and beta-hydroxy-acyl-CoA
      dehydrogenase activity were higher (49% and 35%, respectively, P<0.05) in trained
      compared with untrained subjects. Both lean body mass and maximal oxygen uptake
      were significantly correlated to whole-body peak fat oxidation (r(2)=0.57,
      P<0.001), but leg muscle oxidative capacity was not correlated to whole-body peak
      fat oxidation. In conclusion, whole-body peak fat oxidation occurred at a higher
      relative exercise load in trained compared with untrained subjects. Whole-body
      peak fat oxidation was not significantly related to leg muscle oxidative
      capacity, but was related to lean body mass and maximal oxygen uptake. This may
      suggest that leg muscle oxidative activity is not the main determinant of whole
      body peak fat oxidation.

PMID- 16643202
TI  - Unresolved issues in diagnosis and management of inherited bleeding disorders in
      the perinatal period: a White Paper of the Perinatal Task Force of the Medical
      and Scientific Advisory Council of the National Hemophilia Foundation, USA.
AB  - Haemophilia and inherited bleeding disorders in newborns and their carrier
      mothers pose unique challenges. The pattern of bleeding and the causes and risk
      factors for bleeding are decidedly different than an older child or an adult with
      haemophilia/inherited bleeding disorder. This document outlines the needs for
      further research and education, summarizes the state of the art background
      information and provides guidance regarding research, education and access to
      care issues in this population.

PMID- 16643203
TI  - Continuous infusion of factor concentrates in children with haemophilia A in
      comparison with bolus injections.
AB  - Although the concept of continuous infusion (CI) of factor concentrates is well
      known, prospective paediatric data are rare. We present a prospective open
      labelled non-randomized study focusing on safety, efficacy and factor VIII
      (FVIII) usage compared with bolus injections (BI) in children. In 43 consecutive
      patients (0.5-17 years; median: 9.6) undergoing different operations, CI was
      started with an initial FVIII-bolus of 70 IU kg(-1) bodyweight, followed by a
      median infusion rate of 4.4 IU kg(-1) h(-1) (range: 2.8-9.5) dose adjusted for
      daily FVIII levels (target: 60-80%). No direct serious adverse events occurred;
      however, two out of 43 patients, both from the group of four patients with less
      than 20 exposure days (ED) before starting CI, developed a high-responding
      inhibitor. Two CI patients showed mild thrombophlebitis or rash. Infusion rates
      needed to achieve adequate FVIII levels were highly predictable and could be
      reduced because of decreasing FVIII clearance. Bleeding, requiring additional
      boli, was observed in eight out of 43 patients. Therapy duration and factor usage
      of CI were influenced by the procedure, but not by the product used or
      thrombophilia. Twelve of these CI patients were compared with 12 contemporary
      consecutive age- and procedure-matched BI patients. Compared with BI patients, CI
      patients saved 30% FVIII (812.9 vs. 563.2 IU kg(-1), P < 0.006). We conclude that
      CI forms a safe and effective method for perioperative care in children and
      reduces factor usage. Because of the unknown risk of inhibitor development, we
      will use CI only in patients beyond 20 ED.

PMID- 16643204
TI  - Rituximab for adolescents with haemophilia and high titre inhibitors.
AB  - Neutralizing alloantibodies (inhibitors) to factor VIII or factor IX develop in
      approximately 25% of patients with haemophilia A and <3% of patients with
      haemophilia B treated with factor concentrate. Patients with high titre
      inhibitors, in whom immune tolerance therapy fails, have few treatment options.
      Targeted anti-B-cell therapy with rituximab (chimeric anti-CD20) has been useful
      in several antibody-mediated autoimmune states. Case reports of rituximab
      treatment in small numbers of haemophilia patients with inhibitors have been
      inconclusive. We describe three adolescent patients with severe haemophilia and
      inhibitors treated with four weekly doses of rituximab, 375 mg m(-2). Treatment
      with rituximab was effective in reducing the inhibitor titre in two of three
      patients. Rituximab may be beneficial for patients with severe haemophilia and
      inhibitors in whom standard therapies have failed, but larger prospective studies
      are required to determine safety, efficacy and predictors of success.

PMID- 16643205
TI  - An illustrative case and a review on the dosing of recombinant factor VIIa in
      congenital factor XI deficiency.
AB  - Recombinant activated factor VII (rFVIIa) has been used in a very limited number
      of patients with severe factor XI (FXI) deficiency. The dose and duration of
      treatment has varied greatly between these case reports. In a few of these cases
      there was also evidence of thrombotic complications. We present here a report on
      one additional patient with congenital FXI deficiency. For two major orthopaedic
      procedures in this patient we used rFVIIa as a single bolus dose followed by
      continuous infusion at a low rate. The data from these treatment episodes,
      together with those from a review of the published cases, lend support to the
      concept of using much lower doses than in haemophilia with inhibitors. A bolus
      dose of 20 microg kg(-1) and thereafter maintenance of the FVII activity at
      approximately 3 IU mL(-1) appears effective and safe.

PMID- 16643206
TI  - Hepatotoxicity of antiretroviral drugs in HIV HCV patients with congenital
      coagulopathies followed at an Haemophilia Unit during a decade.
AB  - The aim of the study was to assess the incidence and the cumulative probability
      of cytolytic and cholestatic hepatotoxicity during antiretroviral treatment in a
      group of HIV HCV haemophiliacs. We evaluated 47 patients that received 246
      courses of antiretroviral treatment [98 courses of pre-highly active
      antiretroviral therapy (pre-HAART) and 148 HAART treatments]. Liver function
      tests were assessed at baseline of each treatment, after 1 month and at least
      every 4 months thereafter. Cytolytic and cholestatic hepatotoxicity was recorded.
      Of the 246 treatments, 28 (12.45%) were followed by cytolytic hepatotoxicity and
      32 (13%) by cholestatic hepatotoxicity. Cytolytic hepatotoxicity was similar in
      HAART (16/148; 10.8%) and in pre-HAART treatment (12/98; 12.2%) and cholestatic
      hepatotoxicity was more frequent in HAART (29/148; 19.6%) than in pre-HAART
      treatment (3/98; 3.1%) (P < 0.001). The actuarial probability of developing
      cytolytic and cholestatic hepatotoxicity at 10 years of onset of antiretroviral
      treatments was 39% and 56%, respectively. Most enzyme elevations were
      asymptomatic, but in eight cases therapy was discontinued or changed and in one
      case a cirrhotic patient died of progressive liver failure. In HIV HCV
      haemophiliacs, the cumulative probability of developing hepatotoxicity during
      follow-up is high and although in the most cases the toxicity is mild, fatal
      cases can occur.

PMID- 16643207
TI  - Exercise may decrease further destruction in the adult haemophilic joint.
AB  - The effect of exercise on adult haemophilic joints was investigated. Forty-six
      subjects with existing joint disease were evaluated and range of motion (ROM) in
      joints was measured. The effect of exercise of large joint ROM in haemophilia was
      evaluated by comparing the ranges of motion in subjects who exercised at least
      three times weekly against those subjects who did not exercise. The exercise
      group showed improvement in the majority of joint ranges of motion compared with
      the non-exercise group (P = 0.003). Thus regular exercise may help reduce further
      destruction in haemophilic joints by strengthening muscle ligaments and tendons
      surrounding the joint thereby protecting them from damage caused by recurrent
      haemarthrotic events.

PMID- 16643208
TI  - Comparative study of validity of clinical, X-ray and magnetic resonance imaging
      scores in evaluation and management of haemophilic arthropathy in children.
AB  - To evaluate joints alterations, we performed clinical examination, X-rays and
      magnetic resonance imaging (MRI) (Denver score) in 165 joints of 40 children with
      severe (n, 32) or moderate (n, 8) haemophilia A or B. All investigated joints had
      a history of more than three bleeds. At evaluation, 25 of 40 haemophilic patients
      were on prophylaxis for the last 1-8 years (mean: 3.5 years). MRI revealed
      chronic synovitis in 55.4% and 50% of joints, which were diagnosed, as normal by
      the clinical scale and plain radiography respectively. Moreover, MRI unmasked
      more profound alterations than those observed by plain radiography in 70% of
      cases. Statistical analysis showed that the clinical and Pettersson scores in
      contrast to the Denver score provide an underestimation of arthritic changes.
      Besides, Denver score did not provide resolution in differentiating stages of
      arthropathy, because of its inherent nature; however, a score of 6 expressing
      severe synovitis seemed to be the cut-off value for the distinction of severe
      cases. Based on MRI findings we intensified prophylaxis in nine children and
      initiated it in another nine children. Five children, who were already on
      prophylaxis complied with our recommendations and eliminated haemorrhages.
      Finally, three boys with severe haemophilic arthropathy in knees underwent
      successful chemical synovectomy with rifampicin.

PMID- 16643209
TI  - Disorders of menstruation and their effect on the quality of life in women with
      congenital factor VII deficiency.
AB  - AIMS AND OBJECTIVES: To review menstrual problems in women with congenital FVII
      deficiency and to study their effect on the quality of life during menstruation
      in women with congenital FVII deficiency. METHOD: 14 women with congenital factor
      VII deficiency registered with the Haemophilia Centre at the Royal Free Hospital
      were interviewed and their case notes reviewed. All women completed Pictorial
      Blood assessment Chart (PBAC) for assessment of menstrual blood loss and a
      quality of life questionnaire during menstruation. Similar questionnaire and PBAC
      was completed by an age matched healthy control group of 23 women. RESULTS:
      Median age of study group was 35 yrs and of control group 34 yrs. Median FVII
      level of the study group was 31.5 IU/dL Two women had severe FVII deficiency
      (FVII level < 10 IU/dL) and 12 women had mild-moderate FVII deficiency. 57% women
      (8/14) from study group had menorrhagia (PBAC score > 100) compared with 17%
      (4/23) women from the control group. Six women (43%) from the study group were
      diagnosed with anaemia due to heavy periods, compared to two (9%) in the control
      group. The quality of life scores during menstruation were significantly worse in
      the women with FVII deficiency, compared to controls. CONCLUSION: Women with
      factor VII deficiency exhibit a spectrum of bleeding symptoms, menorrhagia being
      one of the commonest symptoms. This has adverse effect on their quality of life.

PMID- 16643210
TI  - A modified chromogenic assay for the measurement of very low levels of factor
      VIII activity (FVIII:C).
AB  - A precise and sensitive chromogenic assay for the measurement of very low levels
      of factor VIII (FVIII) in plasma has been developed. The assay is based on
      modifications of a commercially available chromogenic assay. The modifications
      include reduction of sample final dilution factor and prolongation of the
      development period. The modified assay allows accurate and precise measurement of
      FVIII in the range of 0.001-0.02 IU mL(-1). The detection limit is 0.0005 IU mL(
      1) and the quantitation limit is 0.0015 IU mL(-1). This assay can be used in
      research and to study the clinical efficacy of low circulating levels of FVIII in
      haemophilia A patients.

PMID- 16643211
TI  - Predicting severity of haemophilia A and B splicing mutations by information
      analysis.
AB  - Bleeding symptoms and clotting activity vary among mutations that alter mRNA
      splicing of either the factor VIII or factor IX genes. We analyzed splicing
      mutations in both genes for changes in individual information (R(i), in bits)
      involving both donor or acceptor sites. Mutations with low or negative R(i)
      values (<2.4 bits) or significant changes in R(i) (DeltaR(i) > or = 7 bits)
      exhibited either reduced protein activity, increased clotting time and bleeding
      frequency and were predictive of severe disease. Thus, information analysis of
      splicing mutations may be useful in predicting phenotypes in hemophilia.

PMID- 16643212
TI  - Insight into molecular changes of the FIX protein in a series of Italian patients
      with haemophilia B.
AB  - Deficiency or dysfunction of factor IX FIX leads to haemophilia B (HB), an X
      linked, recessive, bleeding disorder. On a molecular basis, HB is due to a
      heterogeneous spectrum of mutations spread throughout the F9 gene. In several
      instances, a cause-effect relation has been elucidated, in others predicted
      possibilities have been offered by crystallography inspection and by software
      constructed models of the protein. The aim of this study was to contribute to the
      understanding of HB molecular pathology. The F9 missense mutations we identified
      in 21 unrelated Italian HB patients by direct sequencing of the whole F9 coding
      regions were inspected for the causative effect they provoked on the ensuing
      transcript, and on the protein structure. Each alteration was studied in order
      to: (i) characterize the defect on the basis of the nature of the mutation; (ii)
      identify the predicted defect that is induced in the gene and (iii) speculate
      about the potential, detrimental effects which upset the protein functionality
      through an idealized FIX model. The resulting data may further contribute to the
      comprehension of the mechanisms underlying the disease.

PMID- 16643213
TI  - Sustained expression of Epstein-Barr virus episomal vector mediated factor VIII
      in vivo following muscle electroporation.
AB  - Haemophilia A treatment is an attractive candidate for gene therapy. The aim of
      haemophilia gene therapy is to obtain long-term therapeutic level of factor VIII
      (FVIII). We investigated Epstein-Barr virus (EBV)-based episomal vector combined
      with in vivo electroporation of naked DNA as a safe, efficient and simple method
      for correcting FVIII deficiency. A combinant FVIII expression EBV-based episomal
      vector pcDNA3-FVIII-EBVR was constructed and expressed in COS-7 cells. Then the
      naked plasmid DNA was injected into the quadriceps of mice following the electric
      pulse stimulation. Our data showed that pcDNA3-FVIII-EBVR expression in
      transfected COS-7 can maintain stably for at least 60 days and the hFVIII:Ag in
      plasma in two pcDNA3-FVIII-EBVR groups mice was higher than that in pcDNA-FVIII
      groups no matter with or without electric pulse stimulation. With the stimulating
      of electric pulse, the FVIII expression in plasma of recipient mice was increased
      two- to fourfolds and can be lasted for at least 90 days. No severe muscle damage
      was detected. So this novel strategy that FVIII expression mediated by EBV
      episomal vector following muscle electroporation is efficient, safe, simple and
      economic and may be applicable to clinical usage.

PMID- 16643214
TI  - Failure of rituximab to induce immune tolerance in a boy with severe haemophilia
      A and an alloimmune factor VIII antibody: a case report and review of the
      literature.
AB  - We report the use of rituximab (MabThera); Roche Grenzach-Wyhlen, Germany) in a 6
      year-old boy with severe haemophilia A and a high titre alloimmune factor VIII
      (FVIII) antibody, which had failed to respond to standard immune tolerance
      therapy. Rituximab was administered in 4 weekly doses with concurrent high-dose
      i.v. immunoglobulin (Flebogamma); Grifols, Barcelona, Spain) followed by daily
      high-dose recombinant FVIII concentrate (Recombinate); Baxter, CA, USA). Despite
      a fall in CD20 positive cell count to undetectable levels the inhibitor
      persisted. We discuss the possible reasons for failure of immune tolerance
      induction and review the literature concerning the use of rituximab for this
      indication.

PMID- 16643215
TI  - Von Willebrand's disease and angiodysplasia treated with thalidomide.
AB  - A 54-year-old man with type IIB VWD and severe angiodysplasia had such a large
      blood loss from the bowel that it was difficult to keep up with transfusion
      requirements. Treatment with factor eight concentrate barely slowed the loss.
      D.D.A.V.P., Octreotide, and recombinant activated Factor VII, tried separately,
      were ineffective. The use of Thalidomide at a dose of 150 mg daily has rendered
      him free from blood loss for the last six months and we suggest would be worth a
      trial in similar cases.

PMID- 16643216
TI  - Paediatric acquired von Willebrand syndrome.

PMID- 16643219
TI  - Patient injuries in response to anaesthetic procedures: cases evaluated by the
      Danish Patient Insurance Association.
AB  - BACKGROUND: In response to medical treatment, side-effects may occur and the
      patient may be injured. In Denmark, a patient is entitled to raise a claim for
      financial compensation and the validity of the claim which, based on defined
      criteria, is decided by the independent Patient Insurance Association (PIA). In
      this study, we investigated the files of the patients who were given financial
      compensation because of an injury caused by an anaesthetic procedure. We wanted
      to find the sort of injuries and the anaesthetic procedures involved and the size
      of financial compensation. METHODS: A retrospective study of the PIA database
      from 1996 to 2002 concerning the speciality anaesthesiology. RESULTS: From 1996
      to 2002, 18,917 patients made a claim and out of these 916 files were related to
      anaesthetic procedures, of which 374 cases resulted in financial compensation. In
      the same period, it is estimated that the total number of anaesthetic procedures
      was approximately 400,000 per year in Denmark. The primary causes for financial
      compensation were nerve lesions in response to regional anaesthesia (epidural,
      spinal, peripheral nerve blockade; n = 132), body positional-related injuries (n
      = 100), complications due to intravascular catheters or needles (n = 39) and
      teeth damage during airway handling (n = 31). After anaesthesia, 12 patients'
      brain functions were impaired probably as a result of prolonged peri-operative
      hypotension and hypoxaemia. Death occurred in 21 cases. The average financial
      compensation was 21,500 euros (0.3% of the total amount from all cases) and in 13
      cases the injury induced severe patient disability and therefore the compensation
      was above 1 million DKr. equal to 150,000 euros. CONCLUSION: In the 6-year period
      1996-2002, 374 patients were given in total 8.0 million euros in financial
      compensation for an injury caused by an anaesthetic procedure. Some anaesthetic
      complications may result in severe disability whereby the financial compensation
      to the suffering patients is high. In this study, we estimate that approximately
      approximately 0.2 per thousand of all patients receiving anaesthesia may develop
      complications that entitle them to financial compensation.

PMID- 16643220
TI  - Application of the mixed venous blood concentration equation in desflurane
      anesthesia.
AB  - BACKGROUND: We have previously proposed an equation derived from Fick's law and
      Lin's concept of effective blood concentration (EBC) to calculate the mixed
      venous blood concentration (MVBC) of isoflurane. Desflurane has a lower blood/air
      partition coefficient than isoflurane and, as such, promotes a faster induction
      and recovery from anesthesia. In this study, we investigated the application of
      the MVBC equation to predict the MVBC of desflurane. METHODS: We maintained
      anesthesia with a fixed inspired concentration (CI) of desflurane (10%) during
      cardiac anesthesia in 11 patients. In order to measure the real concentrations of
      desflurane in mixed venous blood, pulmonary arterial blood samples were collected
      at different time points via a Swan-Ganz catheter for gas chromatographic-mass
      spectrometric determination. The relationship between the calculated
      concentrations and the actual blood sample concentrations of desflurane in mixed
      venous blood was investigated. Lin's EBC method was also used and the results
      were compared with those of MVBC. RESULTS: The calculations from our derived MVBC
      equation and the actual blood concentrations showed a similar kinetic pattern;
      the concentration levels were approximately the same and correlated well (r =
      0.89) during anesthesia. However, the EBC method failed to accurately estimate
      the actual blood concentrations. CONCLUSIONS: The results demonstrate that our
      equation, but not the EBC method, may be useful for estimating pulmonary blood
      concentrations of desflurane. The clinical significance and the importance of the
      method merit further investigation.

PMID- 16643221
TI  - Pre-operative measurement of heart rate variability predicts hypotension during
      general anesthesia.
AB  - BACKGROUND: Peri-operative hymodynamic instability is one of the major concerns
      for anesthesiologists when performing general anesthesia for individuals with
      autonomic dysfunction. The purpose of this study was to examine the potential
      usage of pre-operative measurement of heart rate variability (HRV) in identifying
      which individuals, with or without diabetes, may be at risk of blood pressure
      (BP) instability during general anesthesia. METHODS: We studied 46 patients with
      diabetes and 87 patients without diabetes ASA class II or III undergoing elective
      surgery. Participants' cardiovascular autonomic function and HRV were assessed
      pre-operatively, and hymodynamic parameters were monitored continuously intra
      operatively by an independent observer. RESULTS: Only 6% of the participants were
      classified as having cardiovascular autonomic neuropathy (CAN) based on
      traditional autonomic function tests whereas 15% experienced hypotension. Total
      power (TP, P = 0.006), low frequency (LF, P = 0.012) and high frequency (HF, P =
      0.028) were significantly lower in individuals who experienced hypotension
      compared with those who did not. Multivariate logistic regression analysis
      revealed that TP [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.05
      0.47, P = 0.001] independently predicted the incidence of hypotension, indicating
      that each log ms2 increase in total HRV lowers the incidence of hypotension
      during general anesthesia by 0.15 times. After stepwise multiple linear
      regression analysis (R2= 11.5%), HF (beta = -11.1, SE = 2.79, P < 0.001) was the
      only independent determinant of the magnitude of systolic blood pressure (SBP)
      reduction at the 15th min after tracheal intubation. CONCLUSIONS: Spectral
      analysis of HRV is a sensitive method for detecting individuals who may be at
      risk of BP instability during general anesthesia but may not have apparent CAN
      according to traditional tests of autonomic function.

PMID- 16643222
TI  - Desflurane vs. sevoflurane as the main inhaled anaesthetic for spontaneous
      breathing via a laryngeal mask for varicose vein day surgery: a prospective
      randomized study.
AB  - BACKGROUND: Sevoflurane has become widely used in day surgery; however,
      desflurane may be a valuable alternative even in this setting. This study
      compares emergence from anaesthesia for day surgery with spontaneous breathing
      using either desflurane or sevoflurane. METHODS: This prospective, randomized,
      single-blinded study examined 70 ASA III patients undergoing elective ambulatory
      varicose vein surgery. Primary endpoint was emergence time (cessation of
      anaesthetic gas to communicating). Secondary endpoints included post-operative
      pain, nausea, time to discharge, and patient satisfaction. Patients were
      anaesthetized according to a standardized protocol including multimodal analgesia
      and antiemetic therapy and were randomized to receive sevoflurane or desflurane
      as the main anaesthetic while breathing spontaneously through a laryngeal mask
      airway. Fresh gas flow was oxygen in air 1 : 2 l/min. RESULTS: Intra-operative
      anaesthesia was uneventful apart from airway irritation observed in 5/35
      desflurane and 1/35 sevoflurane patients. Emergence was 25-40% faster in patients
      anaesthetized with desflurane. Pain and post-operative nausea and vomiting (PONV)
      were equally infrequent in both groups. Overall, patient satisfaction was high
      with no difference between the groups. CONCLUSION: Desflurane is associated with
      a faster emergence with no differences during the post-operative course except a
      somewhat higher incidence of airway irritation.

PMID- 16643223
TI  - Genetic background differences between FVB and C57BL/6 mice affect hypnotic
      susceptibility to pentobarbital, ketamine and nitrous oxide, but not isoflurane.
AB  - BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying
      much of the inherited variability in drug response. There have been several
      reports of strain-dependent anesthetic actions in rodents, indicating that
      significant genetic differences exist in the hypnotic and antinociceptive effects
      of various anesthetics. METHODS: Loss of righting reflex was used to compare the
      hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between
      two genetically different populations of mice, C57BL/6 with black hair and
      Friends virus B (FVB) with white hair. RESULTS: C57BL/6 mice were more
      susceptible than FVB mice to the hypnotic effects of ketamine, pentobarbital and
      nitrous oxide. However, the sensitivity to isoflurane did not differ between
      C57BL/6 and FVB mice. CONCLUSION: Genetic background affects the hypnotic
      susceptibility to some anesthetic agents in mice. Our results indicate that there
      may be a different genetic basis for the operation of hypnosis between isoflurane
      and other anesthetics, such as pentobarbital, ketamine and nitrous oxide.

PMID- 16643224
TI  - Evaluation of a new recommendation for improved cuffed tracheal tube size
      selection in infants and small children.
AB  - BACKGROUND: The purpose of this study was to evaluate a new recommendation for
      tracheal tube size selection using second-generation Microcuff paediatric
      endotracheal tubes (PETs) with optimized outer diameter (OD) of the distal tube.
      METHODS: With Ethics Committee approval, patients aged from birth to 5 years,
      requiring general anaesthesia with orotracheal intubation, were included.
      Tracheal tube sizes were selected as follows: internal diameter (ID) 3.0 mm,
      birth (if > or =3 kg) to <6 months; ID 3.5 mm, 6 to <18 months; ID 4.0 mm, 18
      months to <3 years; ID 4.5 mm, 3 to <5 years. Tracheal tubes with the cuff not
      inflated were classified as too large if no air leak was obtained at an airway
      pressure of < or =20 cmH2O. Post-intubation stridor requiring therapy was noted.
      RESULTS: Three hundred and fifty children were studied. Nine tracheal tubes
      (2.6%) were too large and had to be exchanged: in patients requiring tracheal
      tubes of ID 3.0 mm and 3.5 mm, three and four tracheal tubes, respectively, and,
      in patients requiring tracheal tubes of ID 4.0 mm and 4.5 mm, one tracheal tube
      in each group. In three patients (0.9%), post-intubation stridor occurred which
      required therapy. CONCLUSION: The new recommendation presented for the use of
      second-generation Microcuff PETs with improved OD to ID ratio allows the
      selection of cuffed tracheal tubes with larger IDs than previously recommended
      for small children without increased need for tracheal tube exchange or increased
      incidence of post-intubation stridor in these age groups.

PMID- 16643225
TI  - Evaluation of the new Viewmax laryngoscope in a simulated difficult airway.
AB  - BACKGROUND: In this study, we evaluated the learning curve and performance of the
      Viewmax laryngoscope during simulated difficult laryngoscopy in an intubation
      manikin (Laerdal Airway Management Trainer). METHODS: To determine the learning
      curve, 25 anaesthesiologists without previous experience with the Viewmax
      laryngoscope performed 10 successive intubations in an intubation manikin with a
      normal airway. Time to intubation and failed intubation attempts were recorded.
      Another manikin was modified to enable comparison of the Viewmax laryngoscope
      with Macintosh and McCoy laryngoscopes. The time to intubation, number of failed
      intubation attempts, modified Cormack and Lehane (MCL) laryngeal view grading,
      percentage of glottic opening (POGO score), use of gum elastic bougie and
      subjective rating of degree of difficulty were recorded. RESULTS: The learning
      curve for the Viewmax laryngoscope showed a progressive decrease in time to
      successful intubation and reached a plateau at the sixth attempt. In simulated
      difficult laryngoscopy, the Viewmax laryngoscope demonstrated significantly
      better laryngeal view than the Macintosh and McCoy laryngoscopes in terms of MCL
      grading (Macintosh, P = 0.01; McCoy, P < 0.01) and POGO score (Macintosh, P <
      0.01; McCoy, P < 0.01). The time required for intubation in simulated difficult
      laryngoscopy for the Viewmax laryngoscope was significantly longer than that for
      the Macintosh (P = 0.02) and McCoy (P < 0.01) laryngoscopes. There was no
      significant difference in the degree of difficulty, number of failed intubations
      and use of gum elastic bougie. CONCLUSION: When compared with the Macintosh and
      McCoy laryngoscopes in a manikin, the Viewmax laryngoscope appears to improve the
      view of the larynx but requires a longer time for tracheal intubation.

PMID- 16643226
TI  - Propofol formulated with long-/medium-chain triglycerides reduces the pain of
      injection by target controlled infusion.
AB  - BACKGROUND: Propofol is a widely used intravenous anesthetic although its
      injection pain is a common and unpleasant problem. Long-/medium-chain
      triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol
      content is expected to reduce injection pain compared with LCT propofol. Target
      controlled infusion (TCI) differs from conventional induction in the initial
      infusion pattern. During induction using TCI, we investigated injection pain
      caused by two propofol solutions with different triglyceride compositions.
      METHODS: Fifty patients, ASA I-II, with adequate communicative ability, were
      randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and
      with BeComSim (custom-made software) for LCT/MCT. The target blood concentration
      was set at 4 microg/ml for both groups. At 30, 60, and 120 s after the infusion,
      patients were asked questions regarding the severity of pain on a 0-10 pain
      score. The total dose of propofol and the time required to induce anesthesia were
      also investigated. RESULTS: The LCT/MCT propofol group had a larger number of
      pain-free patients and showed lower severity of pain than the LCT group [the
      number of pain-free patients being 11 and 3, respectively (P < 0.05), and median
      maximum pain being 0 and 4.5, respectively (P < 0.01)]. The dose and time
      required for induction were not significantly different between the groups (dose
      of 84 +/- 27 and 80 +/- 24 mg, respectively, and time of 119 +/- 60 and 107 +/-
      55 s, respectively). CONCLUSION: Our study showed that the frequency and severity
      of pain during TCI induction with propofol could be significantly reduced using
      LCT/MCT propofol rather than LCT propofol.

PMID- 16643227
TI  - Volatile anaesthetics depolarize neural mitochondria by inhibiton of the electron
      transport chain.
AB  - BACKGROUND: The mitochondrial membrane potential (DeltaPsim) controls the
      generation of adenosine triphosphate (ATP) and reactive oxygen species, and
      sequesteration of intracellular Ca2+[Ca2+]i. Clinical concentrations of
      sevoflurane affect the DeltaPsim in neural mitochondria, but the mechanisms
      remain elusive. The aim of the present study was to compare the effect of
      isoflurane and sevoflurane on DeltaPsim in rat pre-synaptic terminals
      (synaptosomes), and to investigate whether these agents affect DeltaPsim by
      inhibiting the respiratory chain. METHODS: Synaptosomes were loaded with the
      fluorescent probes JC-1 (DeltaPsim) and Fura-2 ([Ca2+]i) and exposed to
      isoflurane or sevoflurane. The effect of the anaesthetics on the electron
      transport chain was investigated by blocking complex I and complex V. RESULTS:
      Isoflurane 1 and 2 minimum alveolar concentration (MAC) decreased the normalized
      JC-1 ratio from 0.92 +/- 0.03 in control to 0.86 +/- 0.02 and 0.81 +/- 0.01,
      respectively, reflecting a depolarization of the mitochondrial membrane (n = 9).
      Isoflurane 2 MAC increased [Ca2+]i. In Ca2+-depleted medium, isoflurane still
      decreased DeltaPsim while [Ca2+]i remained unaltered. The effect of isoflurane
      was more pronounced than for sevoflurane. Blocking complex V of the respiratory
      chain enhanced the isoflurane- and sevoflurane-induced mitochondrial
      depolarization, whereas blocking complex I and V decreased DeltaPsim to the same
      extent in control, isoflurane and sevoflurane experiments. CONCLUSIONS:
      Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre
      synaptic mitochondria through inhibition of the electron transport chain,
      although isoflurane seems to inhibit mitochondrial function more significantly
      than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause
      ATP synthase reversal.

PMID- 16643228
TI  - Bi-level positive airway pressure ventilation maintains adequate ventilation in
      post-polio patients with respiratory failure.
AB  - BACKGROUND: Patients suffering from post-polio syndrome still contribute
      significantly to the number of patients with chronic respiratory failure
      requiring home mechanical ventilation (HMV). Many of these patients are treated
      either with invasive (tracheostomy) or non-invasive (nasal mask) controlled
      mechanical ventilation i.e. volume-controlled ventilation (VCV). In this group of
      patients, we have previously shown that bi-level pressure support ventilation (bi
      level PSV) decreases the oxygen cost of breathing. The aim of this study was to
      compare the effect of bi-level PSV, with special regard to the adequacy of
      ventilation and the oxygen cost of breathing, during the patients' ordinary VCV
      and spontaneous breathing. METHODS: Eight post-polio patients on nocturnal VCV
      were investigated. Five of them were tracheostomized and three of them used a
      nasal mask. Work of breathing was analysed by assessing differences in oxygen
      consumption (VO2) using indirect calorimetry. Blood gases were obtained regularly
      to assess adequacy of ventilation. RESULTS: Bi-level PSV decreases the oxygen
      cost of breathing in post-polio patients with respiratory failure without
      decreasing ventilation efficiency. Furthermore, PaCO2 decreased significantly
      using this mode of ventilation (P < 0.05). CONCLUSION: In this study, it was
      shown that bi-level PSV reduces the oxygen cost of breathing and gave a
      significant decrease in PaCO2 in PPS patients. These data suggest that bi-level
      PSV ventilation maintains adequate ventilation in patients who suffer from post
      polio syndrome with respiratory failure.

PMID- 16643229
TI  - Small-dose perfluorocarbon reduces the recruitment pressure needed to open
      surfactant-deficient atelectatic lungs.
AB  - BACKGROUND: This study was undertaken to investigate the effect of a small dose
      of perfluorocarbon on the recruitment pressure needed to open atelectatic lung
      areas. METHODS: In 12 Yorkshire pigs (body weight, 9 kg), lung injury was induced
      by whole lung lavage. After 1 h of conventional ventilation, an open lung
      maneuver was performed to obtain PaO2 values equal to the pre-lavage PaO2 values
      (+/-10%). After 1 h of ventilation at the lowest possible airway pressure that
      stabilized the recruited lung volume, the animals were disconnected from the
      ventilator to allow the lung to collapse. Six animals received a 5 ml/kg
      intratracheal dose of perfluorocarbon and a second open lung maneuver was
      performed. Six animals served as controls and received no perfluorocarbon but
      also underwent a second open lung maneuver. RESULTS: In both groups, an open lung
      maneuver resulted in a significant increase in oxygenation. The peak pressures
      needed to open the lung after 1 h of mechanical ventilation in the
      perfluorocarbon and control groups were 43.8 +/- 8.4 cmH2O and 46.6 +/- 4 cmH2O,
      respectively. The addition of perfluorocarbon significantly reduced the opening
      pressure to 34.5 +/- 6.3 cmH2O (P < 0.01), whereas the opening pressure in the
      control group, 45.0 +/- 0.2 cmH2O, did not change. CONCLUSION: The instillation
      of a small amount of perfluorocarbon significantly reduces the opening pressures
      needed to recruit atelectatic lung areas.

PMID- 16643230
TI  - Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total
      knee arthroplasty.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is often associated with a considerable
      amount of post-operative blood loss, necessitating the transfusion of allogeneic
      blood, which can add to the complications. Optimization of strategies to reduce
      the need for blood transfusion is desired. This study was designed to evaluate
      the efficacy of autologous platelet gel and fibrin sealant in unilateral TKA.
      METHODS: Consecutive patients were operated on and assigned to the study and
      control groups. Study group patients (n = 85) were operated on according to our
      standard TKA protocol, with the application of autologous platelet gel and fibrin
      sealant on the wound tissues at the end of surgery. Eighty patients were operated
      on according to the same protocol, but without the use of platelet gel and fibrin
      sealant, and served as the control group. All blood transfusions, occurrence of
      wound leakage, wound healing disturbances and incidences of post-operative
      infections were recorded. RESULTS: Patients in the treatment group had a
      significantly higher post-operative haemoglobin level (11.3 vs. 8.9 g/dl,
      respectively) and a decreased need for allogeneic blood products (0.17 vs. 0.52
      units, respectively) than those in the control group (P < 0.001). The incidences
      of wound leakage and wound healing disturbance were significantly less (P <
      0.001) in patients managed with platelet gel and fibrin sealant. Four patients in
      the control group, who received blood products, developed wound infection. The
      hospital stay was decreased by 1.4 +/- 1.5 days for patients in the treatment
      group (P < 0.001). CONCLUSION: Peri-operatively applied platelet gel and fibrin
      sealant may reduce the incidence of allogeneic blood transfusions and
      complications associated with TKA.

PMID- 16643231
TI  - Practical sources of error in measuring pulmonary artery occlusion pressure: a
      study in participants of a special intensivist training program of The
      Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI).
AB  - BACKGROUND: Physiological data obtained with the pulmonary artery catheter (PAC)
      are susceptible to errors in measurement and interpretation. Little attention has
      been paid to the relevance of errors in hemodynamic measurements performed in the
      intensive care unit (ICU). The aim of this study was to assess the errors related
      to the technical aspects (zeroing and reference level) and actual measurement
      (curve interpretation) of the pulmonary artery occlusion pressure (PAOP).
      METHODS: Forty-seven participants in a special ICU training program and 22 ICU
      nurses were tested without pre-announcement. All participants had previously been
      exposed to the clinical use of the method. The first task was to set up a
      pressure measurement system for PAC (zeroing and reference level) and the second
      to measure the PAOP. RESULTS: The median difference from the reference mid
      axillary zero level was - 3 cm (-8 to + 9 cm) for physicians and -1 cm (-5 to + 1
      cm) for nurses. The median difference from the reference PAOP was 0 mmHg (-3 to 5
      mmHg) for physicians and 1 mmHg (-1 to 15 mmHg) for nurses. When PAOP values were
      adjusted for the differences from the reference transducer level, the median
      differences from the reference PAOP values were 2 mmHg (-6 to 9 mmHg) for
      physicians and 2 mmHg (-6 to 16 mmHg) for nurses. CONCLUSIONS: Measurement of the
      PAOP is susceptible to substantial error as a result of practical mistakes.
      Comparison of results between ICUs or practitioners is therefore not possible.

PMID- 16643232
TI  - Platonin attenuates LPS-induced CAT-2 and CAT-2B induction in stimulated murine
      macrophages.
AB  - BACKGROUND: Platonin, a cyanine photosensitizing dye, is a potent immunomodulator
      that suppresses acute inflammation. Platonin not only inhibits interleukin (IL)
      1beta, IL-6, and tumor necrosis factor (TNF)-alpha production but also improves
      circulatory failure in septic rats. In addition, platonin reduces plasma nitric
      oxide (NO) formation during sepsis. However, the effects of platonin on inducible
      NO synthase (iNOS) and cationic amino-acid transporter (including CAT-2, CAT-2 A,
      and CAT-2B) expressions during sepsis remain uninvestigated. METHODS: Five groups
      of confluent murine macrophages (RAW264.7 cells) were randomly allocated to
      receive a 1-h pretreatment of one of five doses of platonin (0.1 microM, 1
      microM, 10 microM, 100 microM, or 1000 microM) followed by lipopolysaccharide
      (LPS; 100 ng ml(-1)). For negative, positive, and platonin control, three other
      groups of cell cultures were randomly allocated to receive phosphate-buffered
      saline, LPS, or platonin (1000 microM). The cultures were harvested after
      exposing them to LPS for 18 h or a comparable duration in those groups without
      LPS. NO production, L-arginine transport, and expression of the relevant enzymes
      were then evaluated. RESULTS: Platonin significantly attenuated LPS-induced up
      regulation of iNOS expression and NO production in stimulated murine macrophages
      in a dose-dependent manner. Platonin also significantly inhibited up-regulation
      of CAT-2 and CAT-2B expression as well as L-arginine transport in LPS-stimulated
      murine macrophages in a dose-dependent manner. In contrast, CAT-2 A expression in
      murine macrophages was not affected by LPS and/or platonin. CONCLUSIONS: Platonin
      attenuates NO production and L-arginine transport in LPS-stimulated murine
      macrophages possibly through inhibiting iNOS, CAT-2, and CAT-2B expression.

PMID- 16643233
TI  - Low vs. high concentration of levobupivacaine for post-operative epidural
      analgesia: influence of mode of delivery.
AB  - BACKGROUND: Although the use of continuous epidural infusion (CEI) and patient
      controlled epidural analgesia (PCEA) has become commonplace in pain management,
      there is still controversy regarding the relative effects of mass, volume and
      concentration of the local anaesthetic. This prospective study evaluated the
      influence of two concentrations of levobupivacaine on the quality of analgesia in
      two modes of delivery after lower abdominal surgery. METHODS: Eighty-two patients
      were randomly assigned to four groups to receive combined low thoracic epidural
      analgesia and general anaesthesia followed by post-operative CEI or PCEA using
      1.5 or 5 mg/ml levobupivacaine (15 mg/h in CEI and bolus 5 mg, lockout 20 min in
      PCEA). Sensory block, pain scores, levobupivacaine and rescue morphine
      consumption, motor blockade, haemodynamics, side-effects and patient satisfaction
      were registered within 48 h. RESULTS: The four groups were similar with regard to
      demographics, quality of analgesia, morphine consumption and satisfaction rate.
      No difference in the quality of analgesia was observed for the two modes of
      delivery with regard to the concentration of levobupivacaine, but the consumption
      of the local anaesthetic was higher in the CEI groups. The Bromage scores in the
      PCEA groups were reduced to zero for all except one patient, whereas eight
      patients presented scores of one or more in the CEI population. CONCLUSION:
      Levobupivacaine in thoracic epidurals provides an equal quality of post-operative
      analgesia in low and high volume independent of the delivery mode, i.e. CEI or
      PCEA. This is in accordance with the assumption that the total dose of the local
      anaesthetic determines the quality of analgesia.

PMID- 16643234
TI  - Effect of needle insertion site on ilioinguinal-iliohypogastric nerve block in
      children.
AB  - BACKGROUND: Three different sites of needle insertion have been proposed for
      ilioinguinal-iliohypogastric (ILIH) nerve block. This double-blind study was
      designed to assess the quality of analgesia produced from these different sites.
      METHODS: One hundred and thirty-two children of ASA grade I and II were randomly
      allocated into four groups to receive no nerve block (control group, n = 30) or
      ILIH block at 1 cm inferio-medial to the anterior superior iliac spine (ASIS) in
      group IM (n = 34), 1-2 cm medial to the ASIS in group M (n = 34) and 2 cm superio
      medial to the ASIS in group SM (n = 34) with 0.25 ml/kg of 0.25% bupivacaine
      after induction of anaesthesia. Pain was assessed using the All India Institute
      of Medical Sciences (AIIMS) pain discomfort scale (APDS) score. The amount and
      pattern of fentanyl consumed over the ensuing 24-h period was noted. RESULTS:
      APDS score and fentanyl requirement were similar in all the study groups but
      significantly higher until 8 h after surgery in the control group, P < 0.05.
      Twenty-two out of 102 children in the study groups and all patients in the
      control group received additional fentanyl during the post-operative period. Only
      6 out of 22 children required additional fentanyl supplementation beyond the 30
      min interval. Overall failure rate of ILIH nerve block was 6%. CONCLUSION: ILIH
      block can be successfully accomplished from any point if the needle bevel lies
      between the two muscle planes above and below the internal oblique.

PMID- 16643239
TI  - Unilateral bronchospasm following interpleural analgesia.

PMID- 16643240
TI  - Priapism in an infant caused by post-operative analgesia through epidural
      catheter.

PMID- 16643242
TI  - Guidelines on triage and end-of-life decisions in intensive care.

PMID- 16643243
TI  - Pneumomediastinum and retropharyngeal emphysema as complications of food-related
      anaphylactoid reaction.

PMID- 16643244
TI  - Genotoxic effects of anaesthetic agents.

PMID- 16643245
TI  - Ischemic skin lesions and microcirculatory collapse during vasopressin therapy: a
      possible role of the microcirculation?

PMID- 16643248
TI  - Acute myelopathy characterized by crus spasm and periodic foot bounce after
      cervical epidural anesthesia.

PMID- 16643249
TI  - Does computed tomography modify management of traumatic haemothorax?

PMID- 16643250
TI  - Electrical shock in the operating theatre: what to do?

PMID- 16643251
TI  - The effects of pentazocine, buprenorphine and butorphanol on human neutrophil
      functions.

PMID- 16643252
TI  - Stem cell therapy of myocardial dysfunction: are there any anaesthetic
      implications for autologous bone marrow harvest?

PMID- 16643253
TI  - Treatment of a massive pulmonary embolism using pulse-spray thrombolysis in a
      patient with central nervous system infection: a risk or the adequate choice?

PMID- 16643254
TI  - Obturator nerve blockade following '3-in-1' block--the role of motor assessment.

PMID- 16643255
TI  - Effective securement of BIS sensors for optimal monitoring.

PMID- 16643256
TI  - Does the bevel orientation of spinal needles matter?

PMID- 16643257
TI  - Fatal cerebral air embolism after endoscopic retrograde cholangiopancreatography.

PMID- 16643258
TI  - Comparing the predictive value of neural network models to logistic regression
      models on the risk of death for small-cell lung cancer patients.
AB  - Cancer is one of the leading causes of mortality in the developed world, and
      prognostic assessment of cancer patients is indispensable in medical care.
      Medical researchers are accustomed to using regression models to predict patient
      outcomes. Neural networks have been proposed as an alternative with great
      potential. Nonetheless, empirical evidence remains lacking to support the
      application of this technique as the appropriate method to investigate cancer
      prognosis. Utilizing data on patients from two National Cancer Institute of
      Canada clinical trials, we compared predictive accuracy of neural network models
      and logistic regression models on risk of death of limited-stage small-cell lung
      cancer patients. Our results suggest that neural network and logistic regression
      models have similar predictive accuracy. The distributions of individual
      predicted probabilities are very similar. On occasion, however, the prediction
      pairs are quite different, suggesting that they do not always give the same
      interpretations of the same variables.

PMID- 16643259
TI  - Patients' self-report and family caregivers' perception of quality of life in
      patients with advanced cancer: how do they compare?
AB  - This study describes the concordance between advanced cancer patients' self
      report of quality of life and their caregivers' perception of the patients'
      quality of life at two time points. It is often necessary for health
      professionals to rely on information about the patients' quality of life that is
      provided by family caregivers (proxy), even though information from the patients
      is considered 'the gold standard'. Therefore, it is important to establish how
      reliable this proxy information is. Data were collected 4-6 weeks following
      diagnosis of recurrent or progressive disease, and again 12 weeks later. Fifty
      one patients and their caregivers completed the European Organization for
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30),
      version 2.0 at both time points. Descriptive statistics were used to calculate
      patient and caregiver scores and describe the sample. The level of agreement
      between the two scores, the patients' self-report and the family caregivers'
      score, was calculated on the mean scores of each scale. In general, most
      caregivers were able to accurately rate the global quality of life, the level of
      functioning and the degree of symptom distress experienced by the person they
      were caring for, when compared with the patients' self-rating. Caregiver ratings
      for physical domains tended to be more in agreement with those of patients as
      compared with ratings of the psychosocial domains. This study suggests
      information from proxy raters is reliable when the proxy is a family caregiver,
      and this remains true over time.

PMID- 16643260
TI  - Changing trends in the number of deaths from soft tissue sarcoma in Japan, 1955
      2002.
AB  - The incidence and number of deaths from soft tissue sarcoma (STS) have been
      reported to increase in many countries. However, those in Japan have not been
      analysed over a long span of time. The objective of this study was to analyse the
      changing trends in the number of deaths from STS in Japan. We analysed the annual
      trends in the number of deaths from STS from 1955 to 2002 in Japan using the data
      from the Vital Statistics of Japan, Statistics and Information Department,
      Minister's Secretariat, Ministry of Health, Labour and Welfare. Until 2000, the
      number of deaths from STS had increased. The recent value of the annual increased
      ratio of deaths from STS was 0.5%[95% confidence interval (CI): -1.2-2.2%]. Men
      continued to have a higher number of deaths than women. The general trends in age
      standardized death rates were roughly upward before 1995, although the death
      rates tended to decrease thereafter. The number and proportion of deaths at or
      after 60 years of age were increasing. The peak age group of deaths was roughly
      the sixties before 1982, and the seventies after 1983. The individuals in their
      sixties and seventies should be the focus of health promotion activities.

PMID- 16643261
TI  - Use of antiepileptics and tricyclic antidepressants in cancer patients with
      neuropathic pain.
AB  - Using a large US health insurance claims database, we identified all persons aged
      > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or
      =2 medical encounters with diagnoses of painful neuropathies in calendar year
      (CY) 2000; persons with seizure disorders or depression were excluded. We then
      examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and
      other pain-related pharmacotherapy among these selected persons, as proxied by
      pharmacy dispenses. A total of 956 persons were identified who met all entry
      criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the
      most widely used AED (92% of all AED patients); amitriptyline was the most widely
      used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were
      similar in age, gender and the presence of metastases to those who had not
      received these medications; they were more likely to have received other pain
      related therapies, however, including short-acting opioids (73% vs. 53%; P <
      0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs
      appears to be relatively low among cancer patients with painful neuropathies.
      Further research is needed to better understand reasons for this finding, as well
      as its potential implications for pain management in this patient population.

PMID- 16643262
TI  - The role of the multidisciplinary team in recruiting to cancer clinical trials.
AB  - This research analyses factors affecting the accrual of women to two breast
      cancer trials, the British Association of Surgical Oncology (BASO) II trial (a
      treatment trial) and the International Breast cancer Intervention Study (IBIS) (a
      prevention trial). The research sought to identify the factors affecting the
      recruitment of women to breast cancer clinical trials from the multidisciplinary
      teams' and women's perspectives using multiple methods. This paper reports on the
      findings from research undertaken with multidisciplinary teams across the United
      Kingdom and highlights their role in recruiting people to cancer clinical trials.
      The findings contribute to the debate and knowledge on recruitment in a number of
      ways by including the views of key stakeholders concerned with these trials, by
      highlighting the factors affecting recruitment to these two trials, and finally,
      by making recommendations on methods to enhance recruitment.

PMID- 16643263
TI  - Group-format clinical supervision for hospice nurses.
AB  - This paper discusses the aspects of a small research study, which used mixed
      research methods. The study concerned group-format supervision as a means of
      helping five hospice nurses, four women and one man, discuss their work
      experiences. An aim of the study was to understand something of the professional
      work of hospice nurses and how they might best be supported. Ethical
      considerations and some benefits derived by group members from clinical
      supervision are summarized in the context. The research method entailed 12
      sessions of group-format clinical supervision. The discussion explores the
      forming, management and dynamics of a small clinical supervision group. Hospice
      work is emotionally demanding of nurses. Nurses throughout this small study
      thought over issues concerning serious illness, death and bereavement, as well as
      working together as a supervision group. Group-format supervision is potentially
      helpful to nurses examining professional practice. However, group work can be as
      challenging to participants as it is helpful. The discussion concludes with an
      appraisal of the potential gains for nurses from clinical supervision in group
      format. This paper proposes that supervision groups could help hospice nurses to
      identify and explore issues related to professional practice. Adequate
      preparation of nurses, organizational support and the competency of group
      facilitators should be considered critical to safe and effective management of
      professional groups.

PMID- 16643264
TI  - Does routine assessment and real-time feedback improve cancer patients'
      psychosocial well-being?
AB  - This study examined the effectiveness of giving medical oncologists immediate
      feedback about cancer patients' self-reported psychosocial well-being in reducing
      those patients' levels of anxiety, depression, perceived needs and physical
      symptoms. Cancer patients attending one cancer centre for their first visit were
      allocated to intervention (n = 42) or control (n = 38) groups. All patients
      completed a computerized survey assessing their psychosocial well-being while
      waiting to see the oncologist. Intervention patients' responses were immediately
      scored and summary reports were placed in each patient's file for follow-up. A
      total of 48 participants (25 intervention and 23 control) completed the survey
      four times. Intervention patients who reported a debilitating physical symptom at
      visit 2 were significantly less likely to report a debilitating physical symptom
      at visit 3 compared with control patients (OR = 2.8, P = 0.04). Reductions in
      levels of anxiety, depression and perceived needs among intervention patients
      were not significantly different to control patients. Repeated collection and
      immediate feedback of patient-reported health information to oncologists has
      potential to improve patients' symptom control, but has little impact upon
      emotional well-being, including those at high risk. Future research should
      consider providing the feedback to other health professionals and patients, and
      monitor the impact on the process of individual patient care.

PMID- 16643265
TI  - Patients' experiences of completing treatment for colorectal cancer in a Scottish
      District General Hospital.
AB  - A review of the cancer literature from 1990 to 2003 indicated that some patients
      with cancer felt abandoned by healthcare professionals upon completion of
      treatment. With this in mind, a small qualitative study was undertaken to explore
      the experiences of patients completing treatment for colorectal cancer within a
      Scottish District General Hospital. A small purposeful sample of eight
      participants (surgery only n = 4 and surgery with adjuvant chemotherapy n = 4)
      who had completed treatment were recruited. Semi-structured interviews, in a
      venue chosen by the participants (home n = 7; hospital n = 1), were tape-recorded
      and transcribed verbatim. The mean time since completion of treatment was 30
      weeks (range 9-95 weeks). Transcripts were read and reread several times to
      identify categories. By thematic analysis, five categories were identified:
      physical impact of treatment, completion of treatment, support of family and
      friends, impact of healthcare professionals and coping mechanisms. Despite the
      significant physical impact of treatment patients returned to their previous
      lifestyles and status. Although very optimistic and positive when treatment was
      completed, participants reflected upon their cancer recurring. Family and friends
      were the main providers of support during their experiences, and healthcare
      professionals impacted upon participants both positively and negatively. Overall,
      the completion of treatment was described as a 'great feeling' and 'relief', with
      patients reporting that they felt adequately supported by healthcare
      professionals after completion of treatment.

PMID- 16643266
TI  - Women's perceptions of events impeding or facilitating the detection,
      investigation and treatment of breast cancer.
AB  - An integrated network is currently being implemented in the province of Quebec in
      order to improve the cancer care continuum. In this context, formal trajectories
      for cancer patients through healthcare services are being established. The
      investigation of patients' perceptions of the healthcare continuum is essential
      as it allows us to identify the issue of continuity/discontinuity of health
      services. In addition, patients' perceptions of continuity of cancer care should
      be documented since they could influence the implementation of optimal
      trajectories through the healthcare services. An exploratory qualitative study
      was conducted in order to identify events, based on the perceptions of women with
      breast cancer, that made the patient progress more rapidly, facilitating events,
      or more slowly, impeding events, within the cancer care continuum. Two
      consecutive series of women receiving adjuvant radiation therapy in 2002 and 2003
      at the University Hospital of Quebec City were recruited, for a total of 120
      participants. A semi-structured interview was administered in order to identify
      women's perceptions regarding impeding and facilitating events during the
      detection, investigation and treatment periods of cancer, as well as the actors
      and reasons involved. Overall, 64% of women reported having at least one impeding
      event, while 68% reported at least one facilitating event. The periods most
      frequently affected by impeding or facilitating events were the investigation
      period, followed by the treatment period. The main stages affected by impeding or
      facilitating events were the scheduling of an appointment, during the
      investigation period, and the onset of treatment. Impeding events particularly
      affected the scheduling of mammography, the initial exam of the investigation for
      breast cancer, as well as the onset of radiation treatment. On the other hand,
      facilitating events mainly occurred at the time of the scheduling of medical
      consultations with specialists, during the investigation period, and of the onset
      of surgery. Finally, women generally perceived that impeding events were due to a
      lack in the availability of services and that facilitating events resulted from
      human intervention. Patients' perceptions, such as those regarding the importance
      of human intervention in the process of continuity of care, should be taken into
      account by healthcare authorities in charge of implementing cancer control
      programmes.

PMID- 16643267
TI  - Consequences of misdiagnosis of lymphomatoid papulosis.
AB  - We report two patients with lymphomatoid papulosis (LyP), who were initially
      diagnosed as systemic T-cell lymphoma. The patients presented with recurrent self
      healing cutaneous lesions and skin biopsies showed a lymphocytic infiltrate with
      malignant features. Clinico-pathological correlation of findings was not
      performed and results of staging investigations were misinterpreted.
      Consequently, both patients were unnecessarily treated with multi-agent
      chemotherapy, radiotherapy and stem cell/bone marrow transplants and sustained
      long-term adverse effects. The clinical and histological features of LyP are
      described and appropriate management discussed in detail. Factors leading to the
      unnecessary treatment of both patients are examined and several learning points
      highlighted such as the importance of a multidisciplinary approach.

PMID- 16643268
TI  - Forum for Applied Education and Training: Rethinking pain assessment.

PMID- 16643272
TI  - Axonal transport of microtubules: the long and short of it.
AB  - Recent studies on cultured neurons have demonstrated that microtubules are
      transported down the axon in the form of short polymers. The transport of these
      microtubules is bidirectional, intermittent, asynchronous, and occurs at the fast
      rate of known motors. The majority of the microtubule mass in the axon exists in
      the form of longer immobile microtubules. We have proposed a model called 'cut
      and run', in which the longer microtubules are mobilized by enzymes that sever
      them into shorter mobile polymers. In this view, the molecular motors that
      transport microtubules are not selective for short microtubules but rather
      impinge upon microtubules irrespective of their length. In the case of the longer
      microtubules, these motor-driven forces do not transport the microtubules in a
      rapid and concerted fashion but presumably affect them nonetheless. Here, we
      discuss the mechanisms by which the short microtubules are transported and
      suggest possibilities for how analogous mechanisms may align and organize the
      longer microtubules and functionally integrate them with each other and with the
      actin cytoskeleton.

PMID- 16643273
TI  - Microtubule plus end: a hub of cellular activities.
AB  - Microtubules (MTs) are highly dynamic polymers, which control many aspects of
      cellular architecture. Growing MT plus ends accumulate a specific set of
      evolutionary conserved factors, the so-called MT plus-end-tracking proteins
      (+TIPs). +TIPs regulate MT dynamics and the reciprocal interactions of MTs with
      the cell cortex, mitotic kinetochores or different cellular organelles. Most
      +TIPs can directly bind to MTs, but the molecular mechanisms of their specific
      targeting to the growing plus ends remain poorly understood. Recent studies
      suggest that the members of one particular +TIP family, EB1 and its homologues,
      are present in all eucaryotic kingdoms, interact directly with the majority of
      other known plus-end-associated proteins and may be responsible for their
      specific accumulation at the MT tips.

PMID- 16643274
TI  - RNA trafficking in axons.
AB  - A substantial number of studies over a period of four decades have indicated that
      axons contain mRNAs and ribosomes, and are metabolically active in synthesizing
      proteins locally. For the most part, little attention has been paid to these
      findings until recently when the concept of targeting of specific mRNAs and
      translation in subcellular domains in polarized cells emerged to contribute to
      the likelihood and acceptance of mRNA targeting to axons as well. Trans-acting
      factor proteins bind to cis-acting sequences in the untranslated region of mRNAs
      integrated in ribonucleoprotein (RNPs) complexes determine its targeting in
      neurons. In vitro studies in immature axons have shown that molecular motors
      proteins (kinesins and myosins) associate to RNPs suggesting they would
      participate in its transport to growth cones. Tau and actin mRNAs are transported
      as RNPs, and targeted to axons as well as ribosomes. Periaxoplasmic ribosomal
      plaques (PARPs), which are systematically distributed discrete peripheral
      ribosome-containing, actin-rich formations in myelinated axons, also are enriched
      with actin and myosin Va mRNAs and additional regulatory proteins. The
      localization of mRNAs in PARPs probably means that PARPs are local centers of
      translational activity, and that these domains are the final destination in the
      axon compartment for targeted macromolecular traffic originating in the cell
      body. The role of glial cells as a potentially complementary source of axonal
      mRNAs and ribosomes is discussed in light of early reports and recent
      ultrastructural observations related to the possibility of glial-axon trans
      endocytosis.

PMID- 16643275
TI  - Viral strategies for intracellular trafficking: motors and microtubules.
AB  - To overcome barriers to diffusion, many viruses utilize the microtubule
      associated molecular motor cytoplasmic dynein 1 to drive transport towards the
      nucleus of a target cell. Cytoplasmic dynein 1 generates movement towards the
      minus end of microtubules located at the microtubule organizing centre (MTOC), a
      structure that is typically in close proximity to the nucleus. Physiological
      cargoes for cytoplasmic dynein include membranous organelles, protein complexes
      and aggregates of misfolded protein. In this review, we discuss the study of
      microtubule-based translocation of viruses and raise questions about the
      mechanisms for association with and then dissociation from cytoplasmic dynein
      with a goal of understanding whether viruses are seen by the intracellular
      trafficking machinery as functional protein complexes or misfolded protein
      aggregates.

PMID- 16643276
TI  - Effects of dynactin disruption and dynein depletion on axonal microtubules.
AB  - We investigated potential roles of cytoplasmic dynein in organizing axonal
      microtubules either by depleting dynein heavy chain from cultured neurons or by
      experimentally disrupting dynactin. The former was accomplished by siRNA while
      the latter was accomplished by overexpressing P50-dynamitin. Both methods
      resulted in a persistent reduction in the frequency of transport of short
      microtubules. To determine if the long microtubules in the axon also undergo
      dynein-dependent transport, we ascertained the rates of EGFP-EB3 "comets"
      observed at the tips of microtubules during assembly. The rates of the comets, in
      theory, should reflect a combination of the assembly rate and any potential
      transport of the microtubule. Comets were initially slowed during P50-dynamitin
      overexpression, but this effect did not persist beyond the first day and was
      never observed in dynein-depleted axons. In fact, the rates of the comets were
      slightly faster in dynein-depleted axons. We conclude that the transient effect
      of P50-dynamitin overexpression reflects a reduction in microtubule
      polymerization rates. Interestingly, after prolonged dynein depletion, the long
      microtubules were noticeably misaligned in the distal regions of axons and failed
      to enter the filopodia of growth cones. These results suggest that the forces
      generated by cytoplasmic dynein do not transport long microtubules, but may serve
      to align them with one another and also permit them to invade filopodia.

PMID- 16643277
TI  - Expanding the role of the dynein regulatory complex to non-axonemal functions:
      association of GAS11 with the Golgi apparatus.
AB  - The mammalian GAS11 gene is a candidate tumor suppressor of unknown function that
      was previously identified as one of several genes upregulated upon growth arrest.
      Interestingly, although GAS11 homologs in Trypanosoma brucei (trypanin) and
      Chlamydomonas reinhardtii (PF2) are integral components of the flagellar axoneme
      and are necessary for regulating flagellar beat, the GAS11 gene was discovered
      based on its expression in cells that do not assemble a motile cilium. This
      suggests that GAS11 function might not be restricted to the cilium. To
      investigate this possibility, we generated GAS11-specific antibodies and
      demonstrate here that GAS11 is expressed in a variety of mammalian cells that
      lack a motile cilium. In COS7 cells, GAS11 is associated with the detergent
      insoluble cytoskeleton and exhibits a juxtanuclear localization that overlaps
      with the pericentrosomal Golgi apparatus. This localization is dependent upon
      intact microtubules and is cell-cycle regulated, such that GAS11 is dispersed
      throughout the cytoplasm as cells progress through mitosis. GAS11 remains
      associated with Golgi fragments following depolymerization of cytoplasmic
      microtubules but is dispersed upon disruption of the Golgi with brefeldin A.
      These data suggest that GAS11 is associated with the Golgi apparatus. In support
      of this, recombinant GAS11 binds Golgi membranes in vitro. In growth-arrested
      mIMCD3 cells, GAS11 co-localizes with gamma-tubulin at the base of the primary
      cilium. The pericentrosomal Golgi apparatus and base of the cilium both represent
      convergence points for microtubule minus ends and correspond to sites where
      dynein regulation is required. The algal GAS11 homolog functions as part of a
      dynein regulatory complex (DRC) in the axoneme (Rupp and Porter. J Cell Biol
      2003;162:47-57) and our findings suggest that components of this axonemal dynein
      regulatory system have been adapted in mammalian cells to participate in non
      axonemal functions.

PMID- 16643278
TI  - Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role
      for caveolar endocytosis.
AB  - We have investigated the targeting of caveolin to lipid bodies in adipocytes that
      express high levels of caveolins and contain well-developed lipid droplets. We
      observed that the lipid droplets isolated from adipocytes of caveolin-1 knock out
      mice contained dramatically reduced levels of cholesterol, indicating that
      caveolin is required for maintaining the cholesterol content of this organelle.
      Analysis of caveolin distribution by cell fractionation and fluorescent light
      microscopy in 3T3-L1 adipocytes indicated that addition of cholesterol rapidly
      stimulated translocation of caveolin to lipid droplets. The cholesterol-induced
      trafficking of caveolins to lipid droplets was shown to be dynamin- and protein
      kinase C (PKC)-dependent and modulated by src tyrosine kinase activation,
      suggesting a role for caveolar endocytosis in this novel trafficking pathway.
      Consistent with this, caveolae budding was stimulated by cholesterol addition.
      The present data identify lipid droplets as potential target organelles for
      caveolar endocytosis and demonstrate a role for caveolin-1 in the maintenance of
      free cholesterol levels in adipocyte lipid droplets.

PMID- 16643279
TI  - Maintaining low Ca2+ level in the endoplasmic reticulum restores abnormal
      endogenous F508del-CFTR trafficking in airway epithelial cells.
AB  - The most common mutation in cystic fibrosis, F508del, results in cystic fibrosis
      transmembrane conductance regulator protein (CFTR) that is retained in the
      endoplasmic reticulum (ER). Retention is dependent on chaperone proteins, many of
      which, like calnexin, require calcium for optimal activity. Here, we show that a
      limited and a maintained ER calcium level is sufficient to inhibit the F508del
      CFTR/calnexin interaction and to restore the cAMP-dependent CFTR chloride
      transport, thus showing the correction of abnormal trafficking. We used Western
      blot analysis, iodide efflux and calcium measurement techniques applied to the
      human airway epithelial cystic fibrosis cell line CF15 (F508del/F508del). The
      inhibition of ER calcium pump, with thapsigargin, curcumin, 2,5-di(t
      butyl)hydroquinone or cyclopiazonic acid, maintains a threshold levels of calcium
      that is correlated to the recovery of endogenous F508del-CFTR transport activity.
      In particular, cyclopiazonic acid restores a 2-aminoethyoxydiphenyl borate
      sensitive F508del-CFTR trafficking with an EC50 of 915 nm. By contrast, the 1,4,5
      trisphosphate or IP3 receptor activators, i.e., ATP and histamine, while
      transiently emptying the ER intracellular calcium store, did not affect the
      trafficking of F508del-CFTR. Our data suggest that decreasing the ER calcium
      level is not sufficient to restore the defective trafficking of F508del-CFTR,
      whereas decreasing and also maintaining low ER calcium level allow correction of
      defective biosynthetic pathway of endogenous F508del-CFTR in human airway
      epithelial cells.

PMID- 16643280
TI  - Clathrin is important for normal actin dynamics and progression of Sla2p
      containing patches during endocytosis in yeast.
AB  - Clathrin is a major vesicle coat protein involved in receptor-mediated
      endocytosis. In yeast and higher eukaryotes, clathrin is recruited to the plasma
      membrane during the early stage of endocytosis along with clathrin-associated
      adaptors. As coated pits undergo maturation, a burst of actin polymerization
      accompanies and helps drive vesicle internalization. Here, we investigate the
      dynamics of clathrin relative to the early endocytic patch protein Sla2p. We find
      that clathrin is recruited to the cortex prior to Sla2p. In the absence of
      clathrin, normal numbers of Sla2p patches form, but many do not internalize or
      are dramatically delayed in completion of endocytosis. Patches that do
      internalize receive Sla1p late, which is followed by Abp1, which appears near the
      end of Sla2p lifetime. In addition, clathrin mutants develop actin comet tails,
      suggesting an important function in actin patch organization/dynamics. Similar to
      its mammalian counterparts, the light chain (LC) subunit of yeast clathrin
      interacts directly with the coiled-coil domain of Sla2p. A mutant of Sla2p that
      no longer interacts with LC (sla2Delta376-573) results in delayed progression of
      endocytic patches and aberrant actin dynamics. These data demonstrate an
      important role for clathrin in organization and progression of early endocytic
      patches to the late stages of endocytosis.

PMID- 16643281
TI  - Src triggers circular ruffling and macropinocytosis at the apical surface of
      polarized MDCK cells.
AB  - We addressed the role of Src on cortical actin dynamics and polarized endocytosis
      in MDCK cells harboring a thermosensitive v-src mutant. Shifting monolayers
      established at 40 degrees C (non-permissive temperature) to 34 degrees C
      (permissive temperature) rapidly reactivated v-Src kinase, but tight junctions
      and cell polarity resisted for >6 h. At this interval, activated v-src was
      recruited on apical vesicles, induced cortactin-associated apical circular
      ruffles productive of macropinosomes, thereby accelerating apical pinocytosis by
      approximately fivefold. Ruffling and macropinosome formation were selectively
      abrogated by inhibitors of actin polymerization, phosphoinositide 3-kinase,
      phospholipase C, and phospholipase D, which all returned apical pinocytosis to
      the level observed at 40 degrees C, underscoring the distinct control of apical
      micropinocytosis and macropinocytosis. Src promoted microtubule-dependent fusion
      of macropinosomes to the apical recycling endosome (ARE), causing its strong
      vacuolation. However, preservation of tubulation and apical polarity indicated
      that its function was not affected. The ARE was labeled for v-src, Rab11, and
      rabankyrin-5 but not early endosome antigen 1, thus distinguishing two separate
      Rab5-dependent apical pathways. The mechanisms of Src-induced apical ruffling and
      macropinocytosis could shed light on the triggered apical enteroinvasive
      pathogens entry and on the apical differentiation of osteoclasts.

PMID- 16643282
TI  - Cytoplasmic tails of SialT2 and GalNAcT impose their respective proximal and
      distal Golgi localization.
AB  - Complex glycolipid synthesis is catalyzed by different glycosyltransferases
      resident of the Golgi complex. Most of them are type II membrane proteins
      comprising a lumenal, C-terminal domain linked to an N-terminal domain (Ntd)
      constituted by a short cytoplasmic tail (ct), a transmembrane, and a lumenal stem
      regions. They concentrate selectively in different sub-Golgi compartments, in an
      overlapped manner, acting in succession in the addition of sugars to acceptor
      glycolipids. The Ntds are sufficient to localize glycosyltransferases in the
      Golgi complex, but it is not clear whether they also confer selective
      concentration in sub-Golgi compartments. Here, we studied whether the Ntd of
      SialT2, localized in the proximal Golgi, and the one of GalNAcT, a trans/TGN
      Golgi-concentrated enzyme, concentrate reporter proteins in the corresponding sub
      Golgi compartment. The sub-Golgi concentration of the Ntds fused to spectral
      variants of the GFP was determined in CHO-K1 cells from their behavior upon
      addition of brefeldin A. Fluorescence microscopy and subcellular fractionation
      showed that the SialT2 Ntd concentrates in a proximal sub-Golgi compartment - and
      that of GalNAcT in TGN elements. Exchanging the transmembrane region and the cts
      of SialT2 and GalNAcT indicates that information for proximal or distal Golgi
      concentration is associated with the cts.

PMID- 16643283
TI  - Subcellular localization of mammalian type II membrane proteins.
AB  - Application of a computational membrane organization prediction pipeline, MemO,
      identified putative type II membrane proteins as proteins predicted to encode a
      single alpha-helical transmembrane domain (TMD) and no signal peptides. MemO was
      applied to RIKEN's mouse isoform protein set to identify 1436 non-overlapping
      genomic regions or transcriptional units (TUs), which encode exclusively type II
      membrane proteins. Proteins with overlapping predicted InterPro and TMDs were
      reviewed to discard false positive predictions resulting in a dataset comprised
      of 1831 transcripts in 1408 TUs. This dataset was used to develop a systematic
      protocol to document subcellular localization of type II membrane proteins. This
      approach combines mining of published literature to identify subcellular
      localization data and a high-throughput, polymerase chain reaction (PCR)-based
      approach to experimentally characterize subcellular localization. These
      approaches have provided localization data for 244 and 169 proteins. Type II
      membrane proteins are localized to all major organelle compartments; however,
      some biases were observed towards the early secretory pathway and punctate
      structures. Collectively, this study reports the subcellular localization of 26%
      of the defined dataset. All reported localization data are presented in the
      LOCATE database (http://www.locate.imb.uq.edu.au).

PMID- 16643284
TI  - Knowledge of Brazilian general dentists and endodontists about the emergency
      management of dento-alveolar trauma.
AB  - The purpose of this study was to determine Brazilian dentists' knowledge of
      emergency management of dento-alveolar trauma. A two-part questionnaire
      containing questions on demographic data and knowledge were mailed to 230 general
      dental practitioners (GDPs) and 70 endodontists. Questionnaires were returned by
      42.6% of the GDPs and 62.8% of the endodontists. The survey data were
      statistically analyzed using Mann-Whitney U-test for practitioners' knowledge and
      Pearson's correlation coefficient for association between knowledge scores and
      practitioner age or years since graduation. The mean knowledge score of
      endodontists was significantly greater than for GDPs (P<0.0001). Dentists with
      trauma experience in their practices and those who had attended postgraduate
      courses on dental trauma had a significant higher mean knowledge score. In
      contrast, there was a poor correlation between the knowledge score and the ages
      of the respondents (r=0.086) or the years since graduation (r=0.108). In
      conclusion, this survey showed a poor knowledge of dental trauma management among
      the surveyed dentists and highlights the need to develop strategies to improve
      the knowledge base in this area of dentistry for the benefit of the dental trauma
      patient.

PMID- 16643285
TI  - Analysis of 154 cases of teeth with cracks.
AB  - It is well known that cracked teeth occur most frequently in the mandibular
      molars with large or poor restorations, in those over 50 years of age. However,
      with increasing knowledge and experience with cracks of teeth, cracks appear to
      be found frequently in intact teeth without restorations. The aim of this study
      is to analyze the cases of tooth cracks in a dental hospital in a year, and to
      find out the characteristic features of cracks of teeth. For 1 year, each tooth
      that were identified as a cracked tooth was recorded and analyzed in terms of the
      classification of cavity and restorative material, the nature of opposing tooth,
      the location in the arch, the age and gender, and the clinical signs and
      symptoms, and treatment result. Cracked teeth were observed most frequently in
      the teeth with no restorations (60.4%) and with class I restorations (29.2%). The
      most prevalent age was in those over 40 years of age (31.2% in their 40s, 26.6%
      in their 50s) and the prevalence was similar in men (53.9%) and women (46.1%).
      Cracked teeth were found most frequently in the maxillary molars (33.8% in first
      molar, 23.4% in second molar) than in the mandibular molars (20.1% in first
      molar, 16.2% in second molar). 96.1% of the cracked teeth responded to the bite
      test, and 81.1% of the cracked teeth were observed in the mesiodistal direction.
      The prevalence of cracked tooth was highest in the intact teeth with no
      restoration, in maxillary molars, and in those over 40 years of age. When
      examining a intact maxillary posterior tooth that is sensitive to a bite and
      thermal change, crack in the mesiodistal direction need to be considered one of
      the causes.

PMID- 16643286
TI  - Physician and emergency medical technicians' knowledge and experience regarding
      dental trauma.
AB  - The purpose of the present study was to evaluate the knowledge of physicians and
      emergency medical technicians (EMT) regarding primary treatment for dental trauma
      and to assess the experience they have in treating dental injuries. The study
      population consisted of 70 military physicians and EMT during their military
      service. A questionnaire was distributed relating to demographic data, such as
      age, gender, position, and type of military service, as well as the following
      issues: past experience in treating or witnessing dental trauma, former education
      regarding diagnosis and treatment of dental trauma, assessment of knowledge
      regarding dental trauma, etc. Of all participants, only 4 (5.9%), all physicians,
      received education regarding dental trauma. Nevertheless, 42 (61.8%) reported
      they witnessed such an injury during their military service. Dental injuries were
      first seen by the EMT in 41.2% of the cases, by the physician in 25%, and by a
      dentist in only 7.3%. Overall, 58 (85.3%) of the physicians and EMT stated that
      it was important to educate the primary health care providers regarding diagnosis
      and treatment of dental trauma. Special emphasis should be given to providing
      primary caregivers with the relevant education to improve their knowledge and
      ability of dealing with diagnosis and treatment of dental trauma.

PMID- 16643287
TI  - Mouthguard utilization rates during sport activities in Ankara, Turkey.
AB  - The objective of this study was to determine the attitudes towards mouthguard use
      in Ankara, Turkey. In the first part of this study, an eight-item questionnaire
      was distributed to 22 coaches from 15 secondary schools randomly selected from
      five municipalities of Ankara, Turkey. The questionnaire sought information on
      how much coaches know regarding mouthguards and how often children and
      adolescents of the ages 11-18 use mouthguards. The second part of the study was
      based on the data obtained from direct interviews answered by 121 university
      athletes of three different sport modalities (football, ice hockey and martial
      arts). The purpose of this part of the study was to determine the rate of
      mouthguard use and the frequency and type of oral trauma in these athletes. The
      result of the coaches' questionnaires revealed that; none of the 11-18 years old
      children and adolescents used mouthguards while participating in sports. Of the
      coaches, 77.2% had seen orofacial trauma in this age group during sport
      activities and 95.5% of the coaches believed that mouthguards prevented oral
      injuries. Of the coaches, 72.7% reported that children and adolescents should use
      mouthguards in sport activities. The second part of the study showed that
      although all of the athletes owned mouth-formed type of mouthguards, the
      utilization rate was 74.4%. Of all players, 13.2% had suffered from one or more
      form of oral injury while not wearing mouthguards. The results show that in
      Turkey, the use of mouthguards has not become widespread in sports. It can be
      concluded that regular mouthguard use in sports should be encouraged in Turkey.

PMID- 16643288
TI  - Biomechanical effects of splint types on traumatized tooth: a photoelastic stress
      analysis.
AB  - This study was undertaken to assess the effect of splint type on stresses
      occurring around traumatized tooth by photoelastic stress analysis. Three semi
      rigid splint types--a wire-composite splint, fiberglass splint and titanium
      trauma splint--were utilized for comparisons. Extracted left upper central and
      lateral incisors and the canine tooth of an otherwise healthy patient were
      embedded equidistantly in photoelastic resin. For all cases studied, a static
      axial and 20 degrees oblique force of 100 N was applied on the lateral incisor in
      separate sessions. The experiments were undertaken without any splint application
      (unsplinted, control) after which the splints, adhesively bonded to the labial
      aspects of teeth, were consecutively tested. During each loading sequence,
      generation of isochromatic fringes was observed in the field of a polariscope,
      and photographed by a digital camera. Quantification of fringes was performed on
      magnified images, transferred to a PC. Under vertical loading, the highest
      stresses in the apical regions were observed for the unsplinted and ribbond
      splint groups, whereas the lowest fringes occurred with the use of orthodontic
      wire as a splinting medium. Titanium trauma splint had absolutely no effect on
      reduction of stresses, as the fringe orders were slightly higher than the
      unsplinted lateral tooth. The use of orthodontic wire resulted in lowest fringe
      orders around the traumatized tooth.

PMID- 16643289
TI  - Anterior palatal mouthguard margin location and its effect on shock-absorbing
      capability.
AB  - The purpose of this study was to evaluate the influence of a mouthguard's (MGs)
      anterior palatal margin location on its shock absorbing capability. A simulation
      study was conducted on a maxillary phantom model with maxillary teeth, bone, and
      soft tissue. Miniature strain gauges were attached to the labial and palatal
      surfaces of the right central incisor as well as the bone surface on the palatal
      side. MGs were made with ethylene vinyl acetate sheets, with thickness of 2.0,
      3.0, and 4.0 mm, using a pressure-forming machine. The locations of the anterior
      palatal MG margins were set at 4.0, 2.0, and 0 mm from the cervical margin in
      three experimental configurations. The control situation was without a MG. A
      calibrated 7N of shock was applied to the middle portions of the labial and
      palatal surfaces of the central incisor. The amount of tooth deflection was
      evaluated. The results were analyzed with one-way anova accompanied by the
      Scheffe's test and multiple regression analysis (P<0.05), designating the strain
      as the dependent value. The results indicated that the thickness rather than the
      location of the anterior palatal margin of the MG has a significant influence on
      the reduction of tooth deflection against a horizontal blow.

PMID- 16643290
TI  - Exposed human pulp caused by trauma and/or caries in primary dentition: a
      histological evaluation.
AB  - The aim of this study was to compare the pulpal reactions after exposure due to
      trauma and/or caries and to suggest the appropriate treatment options for the
      management of pulp, in the light of the histological findings in the primary
      teeth. Fifteen primary maxillary incisors with pulpal exposure were examined with
      light microscope in a blind study. After the histological evaluation, teeth were
      divided into three groups for the etiological factors due to the exposure
      according to the patient's files: trauma group, caries group and caries and
      trauma group. The inflammatory infiltration was diminished from the pulp chamber
      towards the apical third of the root canal in all of the examined teeth. Teeth in
      the trauma group presented fewer inflammatory cells in the root canal in
      comparison with other groups. It was concluded that the teeth with traumatic pulp
      exposure were considered as more likely to respond positively to pulpotomy
      technique. Pulpectomy or extraction seemed to be indicated for the decayed or
      decayed and traumatically injured teeth.

PMID- 16643291
TI  - Comparison of fracture resistance in root canals of immature sheep teeth after
      filling with calcium hydroxide or MTA.
AB  - Thirty immature sheep incisor teeth were tested for their fracture resistance
      after various treatment modalities using calcium hydroxide (CH) or a mineral
      trioxide aggregate material (MTA) as a root filling. The incisors, having
      approximately 80% of their root growth completed, were removed from jaws of
      slaughtered sheep and divided into four experimental groups. The pulps were
      extirpated from all the teeth through the open apexes. (a) Saline group: the
      teeth were preserved in saline for 100 days at 6 degrees C. (b) CH group: the
      root canals were filled with CH and sealed apically with IRM and stored as above.
      (c) MTA group: the canals were filled with MTA and stored as above. (d) CH+MTA
      group: the canals were filled with CH and sealed with IRM. After 30 days, the CH
      was replaced with MTA and stored as above. At the end of the 100-day storage
      period, all teeth were embedded in plaster of Paris and tested for fracture
      strength at the cervical area in an Instron testing machine. The results showed a
      decrease in fracture resistance (a) of the incisors with CH in the root canals
      after 100 days of storage, compared to (b) teeth stored in intracanal saline and
      (c) teeth with 30 days of CH and then filled with MTA, and (d) those filled with
      MTA in the canals. In conclusion, when CH was kept in the canals of immature
      sheep teeth for only 30 days followed by root filling with MTA there was no
      significant decrease in strength of the root within an observation period of 100
      days. This finding may be of importance in the decision of treatment plans for
      teeth with pulp necrosis and immature root formation.

PMID- 16643292
TI  - Histological evaluation of a replanted tooth retained for 49 years.
AB  - A maxillary incisor that had been replanted immediately after avulsion 49 years
      previously was evaluated histologically after extraction. The histological
      evaluation revealed resorption of the apical root surface, depositions in cement
      with different phases and mineral density, and histological changes in the
      periodontal ligament.

PMID- 16643293
TI  - Displacement and pulpal involvement of a maxillary incisor associated with a
      talon cusp: report of a case.
AB  - The talon cusp is a relatively uncommon dental anomaly manifested as an accessory
      cusp-like structure on the crown of anterior teeth. The presence of a talon cusp
      can cause clinical problems. This article reports the case of a patient
      presenting a talon cusp affecting the permanent maxillary right central incisor
      causing clinical problems related to caries, displacement of the tooth, occlusal
      position and tendency to dental traumatism. The management of this tooth included
      caries removal and reduction of the cusp. Pulp-capping with calcium hydroxide was
      required because of the presence of pulp horn extensions in the talon cusp.

PMID- 16643294
TI  - Surgical removal and immediate reattachment of coronal fragment embedded in lip.
AB  - This case describes a patient with a traumatic crown fracture of an upper
      incisor, associated with a laceration wound in the lower lip, showing local
      oedema. While palpating the tissues of the lower lip we felt the presence of a
      foreign body. This was confirmed by a radiograph of the lip that showed a
      radiopaque material, being similar to the coronal fragment of the fractured
      incisor. It was successfully surgically removed and immediately reattached using
      a composite adhesive technique. At the follow-up of 1 year later the vitality
      test on the teeth was positive and neither one of the two traumatized teeth
      showed any sign of discoloration.

PMID- 16643295
TI  - Orofacial injury in a Brazilian professional basketball player: case report.
AB  - The frequency of dental trauma has increased among children and athletes of all
      ages who play contact sports. This kind of trauma may result in irreversible
      damage to the patient. The aim of this report is to present a case of an
      orofacial trauma involving a professional basketball player who was elbowed by
      another player. The athlete reported loss of sensitivity in three teeth and
      computerized tomography showed fractures in three points of the malar bone. After
      the incident and dental follow-up, the player was made aware of the need to wear
      a mouthguard.

PMID- 16643296
TI  - The promise and the potential consequences of the global transport of mycorrhizal
      fungal inoculum.
AB  - Advances in ecology during the past decade have led to a much more detailed
      understanding of the potential negative consequences of species' introductions.
      Moreover, recent studies of mycorrhizal symbionts have led to an increased
      knowledge of the potential utility of fungal inoculations in agricultural,
      horticultural and ecological management. The intentional movement of mycorrhizal
      fungal species is growing, but the concomitant potential for negative ecological
      consequences of invasions by mycorrhizal fungi is poorly understood. We assess
      the degree to which introductions of mycorrhizal fungi may lead to unintended
      negative, and potentially costly, consequences. Our purpose is to make
      recommendations regarding appropriate management guidelines and highlight top
      priority research needs. Given the difficulty in discerning invasive species
      problems associated with mycorrhizal inoculations, we recommend the following.
      First, careful assessment documenting the need for inoculation, and the
      likelihood of success, should be conducted prior to inoculation because
      inoculations are not universally beneficial. Second, invasive species problems
      are costly and often impossible to control by the time they are recognized. We
      recommend using local inoculum sources whenever possible. Third, non-sterile
      cultures of inoculum can result in the movement of saprobes and pathogens as well
      as mutualists. We recommend using material that has been produced through sterile
      culture when local inoculum is not available. Finally, life-history
      characteristics of inoculated fungi may provide general guidelines relative to
      the likelihood of establishment and spread. We recommend that, when using non
      local fungi, managers choose fungal taxa that carry life-history traits that may
      minimize the likelihood of deleterious invasive species problems. Additional
      research is needed on the potential of mycorrhizal fungi to spread to non-target
      areas and cause ecological damage.

PMID- 16643297
TI  - Genetic evidence of frequent long-distance recruitment in a vertebrate-dispersed
      tree.
AB  - The importance of dispersal for the maintenance of biodiversity, while long
      recognized, has remained unresolved. We used molecular markers to measure
      effective dispersal in a natural population of the vertebrate-dispersed
      Neotropical tree, Simarouba amara (Simaroubaceae) by comparing the distances
      between maternal parents and their offspring and comparing gene movement via seed
      and pollen in the 50 ha plot of the Barro Colorado Island forest, Central Panama.
      In all cases (parent-pair, mother-offspring, father-offspring, sib-sib) distances
      between related pairs were significantly greater than distances to nearest
      possible neighbours within each category. Long-distance seedling establishment
      was frequent: 74% of assigned seedlings established > 100 m from the maternal
      parent [mean = 392 +/- 234.6 m (SD), range = 9.3-1000.5 m] and pollen-mediated
      gene flow was comparable to that of seed [mean = 345.0 +/- 157.7 m (SD), range
      57.6-739.7 m]. For S. amara we found approximately a 10-fold difference between
      distances estimated by inverse modelling and mean seedling recruitment distances
      (39 m vs. 392 m). Our findings have important implications for future studies in
      forest demography and regeneration, with most seedlings establishing at distances
      far exceeding those demonstrated by negative density-dependent effects.

PMID- 16643298
TI  - Variable interaction strengths stabilize marine community pattern.
AB  - High variability in the strength of species interactions is usually considered a
      source of unstable or unpredictable community patterns. However, recent
      theoretical work suggests that some types of variance in interaction strength may
      actually promote stability. Here we provide the first empirical evidence that
      highly variable, context-dependent species interaction strengths and resilient
      community patterns can be two sides of the same coin. Field experiments show that
      a persistent rocky intertidal seascape is remarkably resilient to multiple
      sources of environmental stochasticity largely because of scale dependent and
      variable species interaction strengths. Biological interactions exert a
      stabilizing effect because their intensity varies systematically with changes in
      both physical sources of mortality of established species, as well as recruitment
      of new individuals. Strong variation in species interaction strengths with
      disturbance size and environmental conditions is ubiquitous in nature.
      Elucidating when this context dependency will be stabilizing is critical to
      predict community-level responses to anthropogenic disturbances.

PMID- 16643299
TI  - Experimental support of the scaling rule for demographic stochasticity.
AB  - A scaling rule of ecological theory, accepted but lacking experimental
      confirmation, is that the magnitude of fluctuations in population densities due
      to demographic stochasticity scales inversely with the square root of population
      numbers. This supposition is based on analyses of models exhibiting exponential
      growth or stable equilibria. Using two quantitative measures, we extend the
      scaling rule to situations in which population densities fluctuate due to
      nonlinear deterministic dynamics. These measures are applied to populations of
      the flour beetle Tribolium castaneum that display chaotic dynamics in both 20-g
      and 60-g habitats. Populations cultured in the larger habitat exhibit a
      clarification of the deterministic dynamics, which follows the inverse square
      root rule. Lattice effects, a deterministic phenomenon caused by the discrete
      nature of individuals, can cause deviations from the scaling rule when population
      numbers are small. The scaling rule is robust to the probability distribution
      used to model demographic variation among individuals.

PMID- 16643300
TI  - Size and scaling of predator-prey dynamics.
AB  - We propose a scaled version of the Rosenzweig-MacArthur model using both Type I
      and Type II functional responses that incorporates the size dependence of
      interaction rates. Our aim is to link the energetic needs of organisms with the
      dynamics of interacting populations, for which survival is a result of a game
      theoretic struggle for existence. We solve the scaled model of predator-prey
      dynamics and predict population level characteristics such as the scaling of
      coexistence size ranges and the optimal predator-prey size ratio. For a broad
      class of such models, the optimal predator-prey size ratio given available prey
      of a fixed size is constant. We also demonstrate how scaling predictions of prey
      density differ under resource limitation vs. predator drawdown. Finally, we show
      how evolution of predator size can destabilize population dynamics, compare
      scaling of predator-prey cycles to previous work, as well as discuss possible
      extensions of the model to multispecies communities.

PMID- 16643301
TI  - Differential support of lake food webs by three types of terrestrial organic
      carbon.
AB  - Organic carbon inputs from outside of ecosystem boundaries potentially subsidize
      recipient food webs. Four whole-lake additions of dissolved inorganic 13C were
      made to reveal the pathways of subsidies to lakes from terrestrial dissolved
      organic carbon (t-DOC), terrestrial particulate organic carbon (t-POC) and
      terrestrial prey items. Terrestrial DOC, the largest input, was a major subsidy
      of pelagic bacterial respiration, but little of this bacterial C was passed up
      the food web. Zooplankton received <2% of their C from the t-DOC to bacteria
      pathway. Terrestrial POC significantly subsidized the production of both
      zooplankton and benthic invertebrates, and was passed up the food web to
      Chaoborus and fishes. This route supplied 33-73% of carbon flow to zooplankton
      and 20-50% to fishes in non-fertilized lakes. Terrestrial prey, by far the
      smallest input, provided some fishes with >20% of their carbon. The results show
      that impacts of cross-ecosystem subsidies depend on characteristics of the
      imported material, the route of entry into the food web, the types of consumers
      present, and the productivity of the recipient system.

PMID- 16643302
TI  - Plant pathogens drive density-dependent seedling mortality in a tropical tree.
AB  - One explanation for the extraordinary diversity of tropical forest trees is that
      density-dependent mortality from herbivores or pathogens puts locally rare
      species at an advantage. Density-dependent mortality of seeds and small seedlings
      is particularly intense in tropical forests, but its causes remain uncertain.
      Here, we show experimentally that pathogens from the Oomycota are associated with
      intense mortality in seedlings of a neotropical tree, Sebastiana longicuspis.
      Seedlings in untreated plots experienced eight times higher mortality compared
      with seedlings in plots treated with fungicide. Mortality was strongly density
      dependent: in fungicide-treated plots survival was unaffected by density, but
      survival in unsprayed plots was over three times higher at low density. Density
      dependent mortality observed in a simultaneous, non-manipulative study was highly
      transient, suggesting that short-term observational studies may underestimate the
      intensity and form of pathogen-induced mortality. If such effects are widespread,
      plant pathogens may play a key role in maintaining and structuring tropical
      diversity.

PMID- 16643303
TI  - Testing metabolic ecology theory for allometric scaling of tree size, growth and
      mortality in tropical forests.
AB  - The theory of metabolic ecology predicts specific relationships among tree stem
      diameter, biomass, height, growth and mortality. As demographic rates are
      important to estimates of carbon fluxes in forests, this theory might offer
      important insights into the global carbon budget, and deserves careful
      assessment. We assembled data from 10 old-growth tropical forests encompassing
      censuses of 367 ha and > 1.7 million trees to test the theory's predictions. We
      also developed a set of alternative predictions that retained some assumptions of
      metabolic ecology while also considering how availability of a key limiting
      resource, light, changes with tree size. Our results show that there are no
      universal scaling relationships of growth or mortality with size among trees in
      tropical forests. Observed patterns were consistent with our alternative model in
      the one site where we had the data necessary to evaluate it, and were
      inconsistent with the predictions of metabolic ecology in all forests.

PMID- 16643304
TI  - Comparing tropical forest tree size distributions with the predictions of
      metabolic ecology and equilibrium models.
AB  - Tropical forests vary substantially in the densities of trees of different sizes
      and thus in above-ground biomass and carbon stores. However, these tree size
      distributions show fundamental similarities suggestive of underlying general
      principles. The theory of metabolic ecology predicts that tree abundances will
      scale as the -2 power of diameter. Demographic equilibrium theory explains tree
      abundances in terms of the scaling of growth and mortality. We use demographic
      equilibrium theory to derive analytic predictions for tree size distributions
      corresponding to different growth and mortality functions. We test both sets of
      predictions using data from 14 large-scale tropical forest plots encompassing
      censuses of 473 ha and > 2 million trees. The data are uniformly inconsistent
      with the predictions of metabolic ecology. In most forests, size distributions
      are much closer to the predictions of demographic equilibrium, and thus,
      intersite variation in size distributions is explained partly by intersite
      variation in growth and mortality.

PMID- 16643305
TI  - Spillover edge effects: the dispersal of agriculturally subsidized insect natural
      enemies into adjacent natural habitats.
AB  - The cross-edge spillover of subsidized predators from anthropogenic to natural
      habitats is an important process affecting wildlife, especially bird, populations
      in fragmented landscapes. However, the importance of the spillover of insect
      natural enemies from agricultural to natural habitats is unknown, despite the
      abundance of studies examining movement in the opposite direction. Here, we
      synthesize studies from various ecological sub-disciplines to suggest that
      spillover of agriculturally subsidized insect natural enemies may be an important
      process affecting prey populations in natural habitat fragments. This contention
      is based on (1) the ubiquity of agricultural-natural edges in human dominated
      landscapes; (2) the substantial literature illustrating that crop and natural
      habitats share important insect predators; and (3) the clear importance of the
      landscape matrix, specifically distance to ecological edges, in influencing
      predator impacts in agroecosystems. Further support emerges from theory on the
      importance of cross-boundary subsidies for within site consumer-resource
      dynamics. In particular, high productivity and temporally variable resource
      abundance in agricultural systems are predicted to result in strong spillover
      effects. More empirical work examining the prevalence and significance of such
      natural enemy spillover will be critical to a broader understanding of
      fragmentation impacts on insect predator-prey interactions.

PMID- 16643306
TI  - Microsatellites for ecologists: a practical guide to using and evaluating
      microsatellite markers.
AB  - Recent improvements in genetic analysis and genotyping methods have resulted in a
      rapid expansion of the power of molecular markers to address ecological
      questions. Microsatellites have emerged as the most popular and versatile marker
      type for ecological applications. The rise of commercial services that can
      isolate microsatellites for new study species and genotype samples at reasonable
      prices presents ecologists with the unprecedented ability to employ genetic
      approaches without heavy investment in specialized equipment. Nevertheless, the
      lack of accessible, synthesized information on the practicalities and pitfalls of
      using genetic tools impedes ecologists' ability to make informed decisions on
      using molecular approaches and creates the risk that some will use
      microsatellites without understanding the steps needed to evaluate the quality of
      a genetic data set. The first goal of this synthesis is to provide an overview of
      the strengths and limitations of microsatellite markers and the risks, cost and
      time requirements of isolating and using microsatellites with the aid of
      commercial services. The second goal is to encourage the use and consistent
      reporting of thorough marker screening to ensure high quality data. To that end,
      we present a multistep screening process to evaluate candidate loci for inclusion
      in a genetic study that is broadly targeted to both novice and experienced
      geneticists alike.

PMID- 16643307
TI  - Patterns in body mass distributions: sifting among alternative hypotheses.
AB  - Understanding how animals interact with their environment is critical for
      evaluating, mitigating and coping with anthropogenic alteration of Earth's
      biosphere. Researchers have attempted to understand some aspects of these
      interactions by examining patterns in animal body mass distributions. Energetic,
      phylogenetic, biogeographical, textural discontinuity and community interaction
      hypotheses have been advanced to explain observed patterns. Energetic and
      textural discontinuity hypotheses focus upon the allometry of resource use. The
      community interaction hypothesis contends that biotic interactions within
      assemblages of species are of primary importance. Biogeographical and
      phylogenetic hypotheses focus on the role of constraints on the organization of
      communities. This paper examines and organizes these various propositions about
      species body mass distributions and discusses the multiple competing hypotheses,
      how their predictions vary, and possible methods by which the hypotheses can be
      distinguished and tested. Each of the hypotheses is partial, and explains some
      elements of pattern in body mass distributions. The scale of appropriate
      application, relevance and interpretation varies among the hypotheses, and the
      mechanisms underlying observed patterns are likely to be multicausal and vary
      with scale.

PMID- 16643308
TI  - EFNS guidelines on the use of neuroimaging in the management of multiple
      sclerosis.
AB  - Magnetic resonance (MR)-based techniques are widely used for the assessment of
      patients with suspected and definite multiple sclerosis (MS). However, despite
      the publication of several position papers, which attempted to define the utility
      of MR techniques in the management of MS, their application in everyday clinical
      practice is still suboptimal. This is probably related, not only, to the fact
      that the majority of published guidelines focused on the optimization of MR
      technology in clinical trials, but also to the continuing development of modern,
      quantitative MR-based techniques, that have not as yet entered the clinical
      arena. The present report summarizes the conclusions of the 'EFNS Expert Panel of
      Neuroimaging of MS' on the application of conventional and non-conventional MR
      techniques to the clinical management of patients with MS. These guidelines are
      intended to assist in the use of conventional MRI for the diagnosis and
      longitudinal monitoring of patients with MS. In addition, they should provide a
      foundation for the development of more widespread but rational clinical
      applications of non-conventional MR-based techniques in studies of MS patients.

PMID- 16643309
TI  - European Federation of Neurological Societies/Peripheral Nerve Society guideline
      on management of chronic inflammatory demyelinating polyradiculoneuropathy:
      report of a joint task force of the European Federation of Neurological Societies
      and the Peripheral Nerve Society.
AB  - Numerous sets of diagnostic criteria have sought to define chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic
      reviews of treatment have been published. The objective is to prepare consensus
      guidelines on the definition, investigation and treatment of CIDP. Disease
      experts and a patient representative considered references retrieved from MEDLINE
      and Cochrane Systematic Reviews in May 2004 and prepared statements which were
      agreed in an iterative fashion. The Task Force agreed on good practice points to
      define clinical and electrophysiological diagnostic criteria for CIDP with or
      without concomitant diseases and investigations to be considered. The principal
      treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or
      corticosteroids should be considered in sensory and motor CIDP (level B
      recommendation); (2) IVIg should be considered as the initial treatment in pure
      motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective
      plasma exchange (PE) should be considered (level A recommendation); (4) If the
      response is inadequate or the maintenance doses of the initial treatment are
      high, combination treatments or adding an immunosuppressant or immunomodulatory
      drug should be considered (Good Practice Point); (5) Symptomatic treatment and
      multidisciplinary management should be considered (Good Practice Point).

PMID- 16643310
TI  - Epidemiology of headache in Europe.
AB  - The present review of epidemiologic studies on migraine and headache in Europe is
      part of a larger initiative by the European Brain Council to estimate the costs
      incurred because of brain disorders. Summarizing the data on 1-year prevalence,
      the proportion of adults in Europe reporting headache was 51%, migraine 14%, and
      'chronic headache' (i.e. > or =15 days/month or 'daily') 4%. Generally, migraine,
      and to a lesser degree headache, are most prevalent during the most productive
      years of adulthood, from age 20 to 50 years. Several European studies document
      the negative influence of headache disorders on the quality of life, and health
      economic studies indicate that 15% of adults were absent from work during the
      last year because of headache. Very few studies have been performed in Eastern
      Europe, and there are also surprisingly little data on tension-type headache from
      any country. Although the methodology and the quality of the published studies
      vary considerably, making direct comparisons between different countries
      difficult, the present review clearly demonstrates that headache disorders are
      extremely prevalent and have a vast impact on public health. The data collected
      should be used as arguments to increase resources to headache research and care
      for headache patients all over the continent.

PMID- 16643311
TI  - Cabergoline scavenges peroxynitrite enhanced by L-DOPA therapy in patients with
      Parkinson's disease.
AB  - Long-term or high-dose L-DOPA therapy in patients with Parkinson's disease (PD)
      may accelerate degeneration of dopaminergic neurons, possibly by increasing
      oxidative stress. To investigate the effects of cabergoline on peroxynitrite
      mediated oxidative damage caused by L-DOPA, the concentration of 3-nitrotyrosine
      in cerebrospinal fluid (CSF) of 18 PD patients was compared with that in 20
      normal controls. The concentration of 3-nitrotyrosine in patients following L
      DOPA therapy was significantly higher than in untreated PD patients and controls.
      On the other hand, the concentration in PD patients after cabergoline therapy was
      significantly lower than in PD patients after L-DOPA therapy alone. These data
      suggest that cabergoline scavenges peroxynitrite induced by L-DOPA in patients
      with PD.

PMID- 16643312
TI  - Anger, hostility and aggression in the first days of acute stroke.
AB  - In acute stroke patients, anger can disturb management and rehabilitation and
      creates a stressful situation for family, health-care providers and other
      patients. We aim to describe the presence of anger and its association with
      demographic, clinical, psychiatric, lesion variables and functional outcome in
      acute stroke patients. We screened anger prospectively in 202 consecutive acute
      stroke patients (< or =4 days) using eight items from three psychiatric scales
      (Catastrophic Reaction Scale, Mania Rating Scale and Comprehensive
      Psychopathological Rating Scale). Anger was present if the patient scored in at
      least one item. Anger was detected in 71 (35%) patients and 26 of these were
      severely angry (> or =4 points). There was no association between anger and the
      considered variables. Analysis of the items extracted two factors: (i) the
      emotional-cognitive and (ii) the behavioural components of anger. These
      components were independent of each other in 26 patients. In 38 patients we found
      a dissociation between clinical observation and patients' subjective expression.
      Anger was frequent in acute stroke patients. Anger was probably triggered by the
      brain lesion, which interfered with the emotional control. The lack of an
      association with clinical and imaging variables suggests a contribution of
      psychological/psychosocial dimensions.

PMID- 16643313
TI  - Skin biopsy findings and results of neuropsychological testing in the first
      confirmed cases of CADASIL in Norway.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is characterized by mutations in the notch3 gene.
      The mutation can be demonstrated by a gene test. The first group of Norwegian
      patients with CADASIL confirmed by gene testing was recently described. The
      present study includes six of the original nine patients with demonstrated notch3
      mutation plus one patient with symptoms, who had been unwilling to go through
      gene testing. These seven patients underwent skin biopsy for electron microscopy.
      One patient was cognitively too impaired, but six went through neuropsychological
      testing. By electron microscopy characteristic granular osmiophilic material
      (GOM) was detected in all skin biopsies. The material is seen as granular
      deposits in the basal lamina of the smooth muscle layer, often making impressions
      upon adjacent smooth muscle cells. It seems important that blood vessels over a
      certain size (diameter >20 microm) are examined. A varying extent of cognitive
      decline was noted amongst all by neuropsychological testing. In cases with
      multiple infarctions reduction of perceptual speed, visuospatial skills and
      working memory could be demonstrated. Four patients showed executive dysfunction.

PMID- 16643314
TI  - Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients.
AB  - Although there is evidence for correlations between disability and magnetic
      resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of
      structural MRI abnormalities for cognitive dysfunction remains controversial. We
      performed detailed neuropsychological testing, high resolution MRI, and Tc-99m
      ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated
      independently by two investigators for the presence of white matter lesions,
      lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was
      quantified by the use of automatic morphometric assessment of the cortical
      thickness. In addition, laboratory and patients' history data were collected in
      order to assess the individual vascular risk factor profile. The differences in
      cognitive performance between the three patients are neither explained by
      structural-, or functional neuroimaging, nor by the patient-specific vascular
      risk factor profiles. The neuroradiologically least affected patient met criteria
      for dementia, whereas the most severely affected patient was in the best clinical
      and cognitive state. Conventional structural and functional neuroimaging is
      important for the diagnosis of CADASIL, but it is no sufficient surrogate marker
      for the associated cognitive decline. Detailed neuropsychological assessment
      seems to be more useful, particularly with respect to the implementation of
      reliable outcome parameters in possible therapeutic trials.

PMID- 16643315
TI  - Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy.
AB  - Our aim was to test the lateralizing value of a neuropsychological battery
      including several memory tests on a large sample of consecutive patients with
      drug-resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We
      studied 73 right-handed patients (56% males, mean age 35.3 +/- 11.2 years, 49%
      left TLE) aged 16 years or older with normal IQ who underwent a preoperative
      neuropsychological assessment including several memory tests and were seizure
      free after at least 1 year of follow-up. Forty-seven had TLE due to hippocampal
      sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver
      Operating Characteristic (ROC) analysis and discriminant function analysis were
      used to evaluate the lateralization value of selected tests and of the battery as
      a whole, respectively. In patients with TLE secondary to tumors or other lesions,
      no test showed significant lateralizing value. In patients with TLE due to
      hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey
      Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory
      ability. The battery as a whole correctly classified 82% of patients with respect
      to side of epileptogenesis. Our findings suggest that a non-invasive, relatively
      short and unexpensive neuropsychological battery based on memory tests may
      profitably complement other well-established diagnostic procedures such as video
      EEG or magnetic resonance imaging (MRI), at least in patients with drug-resistant
      TLE due to hippocampal sclerosis.

PMID- 16643316
TI  - The role of P300 in the recovery of post-stroke global aphasia.
AB  - Seventeen right-handed patients suffering from global aphasia caused by a recent
      stroke in the left-hemisphere were studied. Passive P300 auditory event related
      potential paradigm was applied every months for 6 months. Aachen subtests were
      used for evaluating comprehension. Only a minority of the patients displayed the
      P300 at the baseline. Those patients had the best outcome at the Aachen
      comprehension subtest. Latency and amplitude changed over time in an
      unpredictable way. The number of patients presenting with the P300 also
      fluctuated, since some patients could regain the potential, whereas some other
      patients could lose that from month to month. Passive P300 is a monitor of
      recovery following global aphasia. A single passive P300 recording is useful for
      prognostic purposes. Repairing mechanisms in the first 6 months have a non-linear
      trend.

PMID- 16643317
TI  - Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene
      mutations in a Danish population of early-onset Parkinson's Disease.
AB  - Autosomal recessive Parkinson's disease (PD) with early-onset may be caused by
      mutations in the parkin gene (PARK2). We have ascertained 87 Danish patients with
      an early-onset form of PD (age at onset < or =40 years, or < or =50 years if
      family history is positive) in a multicenter study in order to determine the
      frequency of PARK2 mutations. Analysis of the GTP cyclohydrolase I gene (GCH1)
      and the tyrosine hydroxylase gene (TH), mutated in dopa-responsive dystonia and
      juvenile PD, have also been included. Ten different PARK2 mutations were
      identified in 10 patients. Two of the patients (2.3%) were found to have
      homozygous or compound heterozygous mutations, and eight of the patients (9.2%)
      were found to be heterozygous. A mutation has been identified in 10.4% of the
      sporadic cases and in 15.0% of cases with a positive family history of PD. One
      patient was found to be heterozygous for both a PARK2 mutation and a missense
      mutation (A6T) in TH of unknown significance. It cannot be excluded that both
      mutations contribute to the phenotype. No other putative disease causing TH or
      GCH1 mutations were found. In conclusion, homozygous, or compound heterozygous
      PARK2 mutations, and mutations in GCH1 and TH, are rare even in a population of
      PD patients with early-onset of the disease.

PMID- 16643318
TI  - LRRK2 mutations are a common cause of Parkinson's disease in Spain.
AB  - Pathogenic mutations in the leucine-rich repeat kinase 2 gene (LRRK2; PARK8) have
      been implicated in autosomal dominant, late-onset parkinsonism. The LRRK2 6055G >
      A (G2019S) mutation is the most common reported to date, and has been observed in
      a number of different European populations. So far, only the LRRK2 4321C > G
      (R1441G) mutation has been identified in the Spanish population. Herein we have
      assessed the frequency of G2019S in a referral-based series of 225 patients with
      Parkinson's disease (PD) from the region of Asturias, Northern Spain. The mutant
      allele was identified in five (2.7%) of the sporadic late-onset patients and was
      not present in control subjects. All carriers displayed genetic profiles
      consistent with the same haplotype, as previously reported for Lrrk2 G2019S
      positive subjects. None of these patients presented with a family history of
      parkinsonism at the time of diagnosis. Thus, approximately 5% of sporadic
      patients with PD from the North of Spain have either Lrrk2 G2019S or R1441G
      substitutions.

PMID- 16643319
TI  - Lesion patterns and etiology of ischemia in the anterior inferior cerebellar
      artery territory involvement: a clinical - diffusion weighted - MRI study.
AB  - The topography and mechanism of stroke in the anterior inferior cerebellar artery
      (AICA) territory are delineated before, but the detailed clinical spectrum of
      lesions involving AICA territory was not studied by diffusion weighted imaging
      (DWI). We reviewed 1350 patients with posterior circulation ischemic stroke in
      our registry. We included patients if the diagnosis of AICA territory involvement
      was confirmed, and DWI, and magnetic resonance angiography were obtained in the 3
      days of symptoms onset. The potential feeding arteries of the AICA territory were
      evaluated on magnetic resonance imaging (MRI) using a three-dimensional rotating
      cineoangiographic method. There were 23 consecutive patients with lesion
      involving AICA territory, six with isolated lesion in the AICA territory, six
      with posterior inferior cerebellar artery, 11 with multiple posterior circulation
      infarcts (MPCIs). The clinical feature of isolated AICA infarct was vertigo,
      tinnitus, dysmetria, ataxia, facial weakness, facial sensory deficits, lateral
      gaze palsy, and sensory-motor deficits in patients with pontine involvement.
      Patients with largest lesion extending to the anterior and inferolateral
      cerebellum showed mixed symptomatology of the lateral medullary (Wallenberg's
      syndrome) and AICA territory involvement. Patients with MPCIs presented various
      clinical pictures with consciousness disturbances and diverse clinical signs
      because of involvement of different anatomical structures. Large-artery
      atherosclerotic disease in the vertebrobasilar system was the main cause of
      stroke in 12 (52%) patients, cardioembolism (CE) in one (4%), and coexisting
      large-artery disease and a source of CE in four (17%). The main cause of stroke
      was atheromatous vertebrobasilar artery disease either in the distal vertebral or
      proximal basilar artery. The outcome was usually good except those with multiple
      lesions. The new MRI techniques and clinical correlations allow better definition
      of the diverse topographical and etiological spectrum of AICA territory
      involvement and associated infarcts which was previously based on pathological
      and conventional MRI studies.

PMID- 16643320
TI  - Computed tomographic changes of the brain and clinical outcome of patients with
      seizures and epilepsy after an ischaemic hemispheric stroke.
AB  - It is not well established whether seizures and epilepsy after an ischaemic
      stroke increase the disability of patients. Seventy-two patients with delayed
      seizures after a hemispheric infarct (37 with a single seizure and 35 with
      epilepsy) were included in the study. The modified Rankin scale was used to
      compare disability of the patients at 1 month after stroke and at 2 weeks after
      single or the last seizure, in case of epilepsy. The size of the X-ray
      hypoattenuation zone was compared on computed tomographic (CT) scans, performed
      in the weeks after the stroke and 1 week after single or repeated seizures.
      Lesion size was determined by superimposing the CT slices on digital cerebral
      vascular maps, on which the contours of the infarct area were delineated. The
      extent of the infarcts was expressed as the percentage fraction of the total
      surface area of the cerebral hemisphere. Groups with a single seizure and with
      epilepsy were mutually compared. Infarcts predominated in the parieto-temporal
      cortical regions. In the overall group the median Rankin score worsened
      significantly after seizures. The average size of the X-ray hypoattenuation zone
      was also significantly increased on the CT scans after the seizures, compared
      with those after stroke, without clear evidence of recent infarction. Mutual
      comparison of patients with a single seizure episode and of those with epilepsy
      showed only a trend of more severe disability and of increase in lesion size in
      the post-stroke epilepsy group. Delayed seizures and epilepsy after ischaemic
      stroke are accompanied by an increase in lesion size on CT and by worsening of
      the disability of the patients. This study does not allow to determine whether
      this is due to stroke recurrence or due to additional damage as a result of the
      seizures themselves.

PMID- 16643321
TI  - The search for cerebral biomarkers of Huntington's disease: a review of genetic
      models of age at onset prediction.
AB  - The mutation causing Huntington's disease is an expanded CAG trinucleotide repeat
      number beyond 35 in the 5' translated region of the gene. The mutation penetrance
      varies widely and depends on the CAG expansion length, the low pathological
      triplet range (36-41) showing a very low penetrance, possibly associated with
      late ages at onset. No research has so far yielded biomarkers for accurately
      predicting either age at onset or disease progression in at risk individuals.
      Specific markers able to follow-up mutation carrier subjects from the pre
      symptomatic stages of life are crucial for testing experimental neuroprotective
      preventive therapies. Nevertheless, the factor accounting for the largest
      percentage of age at onset variation is the expanded repeat number within the
      gene. Over the years, this factor has helped in setting up models for genetically
      predicting age at onset. Once available for practical application in clinics,
      such models allowed phenotype-genotype correlations that were hitherto
      inconceivable. In this review, we discuss how these genetic models have been
      applied in clinical practice and comment on their potential value in searching
      for cerebral biomarkers of disease onset and severity and in designing trials of
      therapeutic drugs.

PMID- 16643322
TI  - Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular
      disorder of unknown etiology, characterized by weakness, muscle wasting,
      fasciculations, and increased reflexes, with conserved intellect and higher
      functions. The neuropathology of ALS is mostly confined to damage of the motor
      neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior
      horns of the spinal cord. However, there is evidence for the involvement of other
      neuronal systems in the disease. In particular, damage of the dopamine neurons
      has been shown by neurochemical and imaging studies in the brain and spinal cord
      of ALS patients. Recent reports suggest that peripheral blood mononuclear cells
      (PBMC) may represent a useful in vivo model to study neurochemical alterations
      that occur in neurodegenerative disorders. Here we demonstrate the significant
      reduction of dopamine transporter immunoreactivity in PBMC of patients affected
      by ALS with respect to healthy subjects. These results extend our knowledge of
      damage of the dopamine system in ALS to peripheral cells. Thus, the original
      concept of ALS as an isolated degeneration of motor neurons seems to extend to a
      more widespread understanding of the disease with involvement of other neuronal
      systems in the central as well as peripheral nervous system.

PMID- 16643323
TI  - Magnetic brainstem stimulation of the hypoglossal nerve in normal subjects.
AB  - Electrophysiological evaluation of motor pathways to the lingual muscles is
      technically challenging. Previous studies utilizing transcranial magnetic
      stimulation (TMS) of the parieto-occipital region with a round coil reported
      difficulties in eliciting tongue motor responses. In this study, we utilized TMS
      with a double cone coil at the posterior head region to obtain tongue motor
      evoked potentials. Our findings suggest activation at or distal to the
      hypoglossal nuclear level, but proximal to the hypoglossal canal region. Our
      method can be usefully applied in future studies of brainstem and cranial nerve
      function.

PMID- 16643324
TI  - Left common and right internal carotid artery occlusion - color-coded duplex
      sonography and magnetic resonance angiography findings.

PMID- 16643325
TI  - Hemiplegia in Lemierre syndrome: a neuroimaging strategy.

PMID- 16643326
TI  - Real-time monitoring of recanalization after intravenous thrombolysis for acute
      ischemic stroke.

PMID- 16643327
TI  - Diagnostic value of CSF 14-3-3 detection in sporadic CJD diagnosis according to
      the age of the patient.

PMID- 16643328
TI  - Impact of the duration of antiplatelet therapy after vertebrobasilar artery stent
      placement.

PMID- 16643329
TI  - Effect of selective LDL-apheresis in a Fabry patient with recurrent strokes.

PMID- 16643330
TI  - Miller Fisher syndrome associated with Burkitt's lymphoma.

PMID- 16643331
TI  - A case of cerebral nocardiosis following brief immunosuppression.

PMID- 16643332
TI  - Per-oral transgastric abdominal surgery.
AB  - Laparoscopic surgery has several advantages over traditional surgery because it
      has been shown to be less invasive. The next logical step in the evolution of
      minimally invasive surgery may be to eliminate all abdominal incisions. The
      natural orifices provide a port of entry via the gastrointestinal tract to the
      peritoneal cavity. This approach would require the creation of a perforation,
      which is considered to be a major complication of endoscopy with significant
      morbidity and mortality. However, there are several recent studies that have
      described the technical feasibility and safety of a per-oral transgastric
      approach to the peritoneal cavity using conventional endoscopes. Theoretically,
      this approach could reduce postoperative abdominal wall pain, wound infection,
      hernia formation, and adhesions. This article aims to summarize the current
      status of transgastric surgery, currently referred to as natural orifice
      transluminal endoscopic surgery (NOTES), and to address some of its future
      challenges.

PMID- 16643333
TI  - Clinical aspects of ulcerative colitis in mainland China.
AB  - Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative
      colitis (UC), is reported to be increasing in incidence and prevalence in
      provinces and cities in mainland China. This article specifically reviews
      clinical features, extra-intestinal manifestations, complications, diagnosis and
      differential diagnosis, and medical treatment of UC. Compared to patients in
      Western countries, more mild to moderate and left-sided colitis cases were
      observed in a nation-wide study in China. Complications included anal fistula,
      anal abscess, anal fissure, severe bleeding, intestinal perforation, intestinal
      obstruction and colonic carcinoma. The extra-intestinal manifestations were
      arthritis/arthralgia, eye and skin disorders and oral ulcers. The high
      specificity of antineutrophil cytoplasmic antibody may useful for distinguishing
      UC from infectious colitis; in addition, serum levels of anti-saccharomyces
      cerevisiae antibody may be helpful for distinguishing between UC and CD. Oral
      sulfasalazine and 5-aminosalicylic acid (ASA) remain the mainstays for the
      management of mild to moderate UC in China. Corticosteroids and immunosuppressive
      agents are also widely used in severe or refractory UC.

PMID- 16643334
TI  - Advances in mechanisms of postsurgical gastroparesis syndrome and its diagnosis
      and treatment.
AB  - Postsurgical gastroparesis syndrome (PGS) is a complex disorder characterized by
      post-prandial nausea and vomiting, and gastric atony in the absence of mechanical
      gastric outlet obstruction, and is often caused by operation at the upper
      abdomen, especially by gastric or pancreatic resection, and sometimes also by
      operation at the lower abdomen, such as gynecological or obstetrical procedures.
      PGS occurs easily with oral intake of food or change in the form of food after
      operation. These symptoms can be disabling and often fail to be alleviated by
      drug therapy, and gastric reoperations usually prove unsuccessful. The cause of
      PGS has not been identified, nor has its mechanism quite been clarified. PGS
      after gastrectomy has been reported in many previous studies, with an incidence
      of approximately 0.4-5.0%. PGS is also a frequent complication of pylorus
      preserving pancreatoduodenectomy (PPPD), and the complication occurs in the early
      postoperative period in 20-50% of patients. PGS caused by pancreatic cancer
      cryoablation (PCC) has been reported about in 50-70% of patients. Therefore, PGS
      has a complex etiology and might be caused by multiple factors and mechanisms.
      The frequency of this complication varies directly with the type and number of
      gastric operations performed. The loss of gastric parasympathetic control
      resulting from vagotomy contributes to PGS via several mechanisms. It has been
      reported that the interstitial cells of Cajal (ICC) may play a role in the
      pathogenesis of PGS. Recent studies in animal models of diabetes suggest specific
      molecular changes in the enteric nervous system may result in delayed gastric
      emptying. The absence of the duodenum, and hence gastric phase III, may be a
      cause of gastric stasis. It was thought that PGS after PPPD might be
      attributable, at least in part, to delayed recovery of gastric phase III, due to
      lowered concentrations of plasma motilin after resection of the duodenum. The
      damage to ICC might play a role in the pathogenesis of PGS after PCC, for which
      multiple factors are possibly responsible, including ischemic and neural injury
      to the antropyloric muscle and the duodenum after freezing of the
      pancreatoduodenal regions or reduction of circulating levels of motilin. As the
      treatment of gastroparesis is far from ideal, non-conventional approaches and non
      standard medications might be of use. Multiple treatments are better than single
      treatment. This article reviews almost all the papers related to PGS from various
      journals published in English and Chinese in recent years in order to facilitate
      a better understanding of PGS.

PMID- 16643335
TI  - Diet and gastric cancer: a case-control study in Shanghai urban districts.
AB  - OBJECTIVE: The incidence rates of gastric cancer in Shanghai urban districts have
      been markedly declining over the past three decades. From 1972 to 2001 the age
      adjusted incidence rates of gastric cancer decreased from 62.0 to 32.5 per
      100,000 in men and from 23.9 to 16.9 per 100,000 in women. This study aimed to
      investigate the relationship between environmental factors, in particular dietary
      factors, and the development of gastric cancer in those who lived in Shanghai
      urban districts for more than 15 years, and to explore the causes that led to the
      reduction of the incidence rates of gastric cancer in Shanghai. METHODS: One
      hundred and eighty-nine patients with gastric cancer and 567 age and sex-matched
      controls were surveyed with a questionnaire. SPSS software package was used to
      perform the univariate and multivariate unconditional logistic regression
      analysis modeling. RESULTS: Vitamin supplements, use of home refrigerators, high
      consumption of fresh fruits and vegetables, bean and dairy products, and good
      meal habits were protective factors against gastric cancer. However, family
      history of cancer, chronic gastric diseases, increased intake of salted, pickled,
      fried and smoked foods, poor meal habits, smoking and alcohol drinking were risk
      factors for gastric cancer. CONCLUSIONS: The reduction of the incidence of
      gastric cancer in Shanghai urban district in the past three decades is closely
      related to environmental factors, in particular dietary factors and wide use of
      home refrigerators.

PMID- 16643336
TI  - Effect of change in an inhibitory neurotransmitter of the myenteric plexus on the
      pathogenetic mechanism of irritable bowel syndrome subgroups in rat models.
AB  - OBJECTIVE: In order to investigate the effect of change in an inhibitory
      neurotransmitter of the myenteric plexus on irritable bowel syndrome (IBS)
      subgroups, the amounts of nitric oxide (NO) in constipation-predominant (C-IBS)
      and diarrhea-predominant (D-IBS) IBS models in rats were studied. METHODS: The D
      IBS model was created in rats by intracolonic instillation of acetic acid and by
      restraint stress. The D-IBS control group underwent intracolonic instillation
      with saline instead. The C-IBS model was created in rats by gastric instillation
      of 0-4 degrees C cool water daily for 14 days. The C-IBS control group underwent
      gastric instillation with saline instead. A blank control group was also made.
      Viscerosomatic sensitivity was assessed with electromyographic (EMG). Abdominal
      contractions induced by distension of a colonically inserted balloon (0-1.6 mL)
      was recorded in rats by implanting electrodes in the abdominal external oblique
      muscle. An India ink gastric instillation experiment was used to detect the bowel
      movement and fecal pellets formation. Histological analysis of colonic tissue was
      performed. Nicotinamide dinucleotide phosphate (NADPH)-diaphorase staining was
      used to detect positive NO neurons in the myenteric plexus. RESULTS: When the
      balloon was distended by high volume, there were significantly more contractions
      of abdominal muscle in D-IBS compared with C-IBS and the control groups (P <
      0.05). When the balloon was distended by low volume, there were significantly
      fewer contractions of abdominal muscle in C-IBS compared with D-IBS and the
      control groups (P < 0.05). The wet weight and water content of the feces expelled
      by the rats in the C-IBS and the C-IBS control groups were significantly lower
      than those in the blank control group (P < 0.05). The time before the first black
      stool in the C-IBS group was significantly longer than that in the blank control
      group and C-IBS control group (P < 0.05). Histological analysis of the colon
      showed no colonic inflammation in any group. The number of NO-positive neurons in
      the C-IBS group was significantly greater than in the D-IBS and control groups (P
      < 0.01), although there was no significant difference in the number of neurons
      between the D-IBS and the control groups (P > 0.05). CONCLUSIONS: Enhanced
      inhibitory neurotransmitter NO in the myenteric plexus of the colon is related to
      IBS subgroups, visceral sensitivity and motility dysfunction. The results reveal
      that NO plays a role in the pathogenetic mechanism of IBS subgroups.

PMID- 16643337
TI  - Analysis of gene expression profile in colon cancer using the Cancer Genome
      Anatomy Project and RNA interference.
AB  - OBJECTIVE: To investigate the changes in the gene expression profile in colon
      cancer to further identify gene markers that may be useful in the management of
      this disease. METHODS: Data from serial analysis of gene expression (SAGE)
      collected by the Cancer Genome Anatomy Project (CGAP) were used to detect the
      difference in gene expression between normal tissue and colon cancer, and were
      further confirmed in a sample of 20 patients using RT-PCR. To identify the
      functions of differential genes in regulating the cell growth of colon cancer,
      RNA interference (RNAi) was used to block one of these genes in the colon cancer
      cell line HCT-116. RESULTS: Expression changes of greater than twofold in two
      SAGE libraries of colon cancer compared to two of normal tissue were observed for
      216 tags of a total of 195,160 transcript tags (54 up-regulated genes and 136
      down-regulated genes). Subsequent analysis of 17 genes by RT-PCR confirmed the
      reliability of this analysis. RNAi-mediated blockage of one of these genes,
      transforming growth factor (TGF)beta1, significantly reduced the growth of a
      colon cancer cell line. CONCLUSIONS: The combination of CGAP analysis and RNAi
      provides an excellent system to rapidly define the specific genes that are up
      regulated in cancer to impact the growth of cancer cells. Further study on these
      differential overexpressed genes may provide gene markers for the detection and
      treatment of colon cancer.

PMID- 16643338
TI  - Expression of gamma-aminobutyric acid and glutamic acid decarboxylases in rat
      descending colon and their relation to epithelial differentiation.
AB  - OBJECTIVE: To detect the expression of gamma-aminobutyric acid (GABA) and
      glutamic acid decarboxylases (GADs; including two isoforms GAD65 and GAD67) in
      the epithelial growth zones of the descending colon in rats, and to investigate
      their relation to epithelial differentiation and proliferation. METHODS: The
      expression of GABA and GADs in rat descending colon was investigated by
      immunofluorescent staining and confocal laser scanning techniques, and goblet
      cells were further investigated by wheat-germ agglutinin histochemistry. In
      addition, GAD65 and GAD67 mRNAs were also detected by reverse transcription
      polymerase chain reaction. Furthermore, evaluation of cell kinetics in colonic
      epithelia was conducted by ABC immunostaining using a monoclonal antibody against
      proliferating cell nuclear antigen (PCNA). RESULTS: Immunoreactive GABA and GADs
      were distributed in the upper third of the crypts and at the luminal surface in
      the rat descending colon. Strong staining for GABA and GADs was localized mainly
      in the cytoplasm of epithelial cells near the neck of the crypts and along the
      luminal surface. In addition, GABA and GAD65 were also detected at the lamina
      propria in colonic mucosa. No staining for GABA or GADs was found in goblet
      cells. GAD65 and GAD67 mRNAs were identified in homogenates of rat descending
      colon. PCNA labeled nuclei were found in the lower two-thirds of the crypts.
      CONCLUSIONS: The expression of GABA and GADs in the maturation and function zones
      of rat descending colon suggests that GABA may be involved in the differentiation
      of colonic epithelial cells.

PMID- 16643339
TI  - Treatment of surgically induced acute liver failure by transplantation of HNF4
      overexpressing embryonic stem cells.
AB  - OBJECTIVE: Tissue-specific stem cells from differentiating embryonic stem (ES)
      cells are both pluripotent and genetically flexible. Recent observations indicate
      that ES cells can differentiate into hepatocytes. Therefore, cell-based therapy
      can potentially be a therapeutic alternative to liver transplantation. In this
      study the treatment of acute liver failure in rats by transplantation of
      hepatocyte nuclear factor 4 (HNF4)-overexpressing ES cells was investigated.
      METHODS: The HNF4 was transfected into ES cells and ES cell clones overexpressing
      HNF4 were selected. The levels of markers of hepatocyte differentiation,
      including albumin, transthyretin, glucose-6-phosphates (G-6-P) and SAPK/ERK
      kinase-1 (SEK1) mRNA, were tested in spontaneously differentiated HNF4
      overexpressing ES cells by reverse transcription-polymerase chain reaction (RT
      PCR). The ultrastructure of the spontaneously differentiated HNF4-overexpressing
      ES cells was examined by electron microscopy. To induce acute liver failure,
      Sprague-Dawley rats were subjected to 90% hepatectomy and given 5% oral dextrose.
      The rats were divided into three groups. The rats in the treatment group (n = 12)
      received intraliver injection of 2 x 10(7) undifferentiated HNF4-overexpressing
      ES cells from the same clone, the rats in control group 1 (n = 12) received 2 x
      10(7) undifferentiated ES cells, and the rats in control group 2 (n = 12)
      received the same volume of media without any cells. RESULTS: All rats in control
      group 1 and control group 2 died within 72 h, while 33% of rats that received
      undifferentiated HNF4-overexpressing ES cells transplantation survived more than
      1 month. Spontaneously differentiated HNF4-overexpressing ES cells only expressed
      transthyretin mRNA. The cells were rich in mitochondrion and catalase-containing
      peroxisomes in ultrastructure. CONCLUSIONS: Transplantation of ES cells could be
      a potential treatment in supporting life during acute liver insufficiency and
      could be a bridge to orthotopic liver transplantation.

PMID- 16643340
TI  - Evaluating the role of serum elastase 1 in the diagnosis of pancreatic cancer.
AB  - OBJECTIVE: To determine the normal value of serum elastase 1 in Chinese adults
      and evaluate its diagnostic value for pancreatic cancer. METHODS: Serum elastase
      1 and CA19-9 were measured in 132 samples, including 39 patients with pancreatic
      cancer, 48 with other gastrointestinal malignancy, 24 with gastrointestinal
      benign disease and 21 healthy adults as normal control. Multiple statistical
      methods including receiver operating characteristics curve and discriminant
      analysis were employed. RESULTS: The established normal range of serum elastase 1
      in Chinese adults was found to be under 4.36 mg/L. Serum elastase 1 increased
      markedly in patients with pancreatic carcinoma of smaller size and/or located in
      the pancreatic head. The sensitivity, specificity and overall accuracy of
      elastase 1 for diagnosis of pancreatic cancer were 61.5%, 75.3% and 71.2%,
      respectively, as compared with 71.8%, 73.1% and 72.7% for CA19-9. Discriminant
      analysis can improve the sensitivity and overall accuracy of elastase 1 to 82.0%
      and 74.2%, respectively, with a slight decline in the specificity to 71.0%.
      CONCLUSIONS: The cutoff value of serum elastase 1 in normal Chinese adults is
      4.36 mg/L. Serum elastase 1 is effective in the diagnosis of pancreatic cancer,
      especially for those of smaller size or in the pancreatic head. Use of
      appropriate statistical methods can help to make the diagnosis more accurate.

PMID- 16643341
TI  - Influence of glutamine on pancreatic blood flow and apoptosis of pancreatic
      acinar in rats with severe acute pancreatitis.
AB  - OBJECTIVE: To investigate the role of glutamine on splanchnic blood flow,
      apoptosis of pancreatic acinar and the underlying mechanism in rats with severe
      acute pancreatitis. METHODS: Forty-eight rats were randomized into two groups:
      the glutamine group (n = 24) and the severe acute pancreatitis group (n = 24).
      Jejunotomy was performed in all rats: the glutamine group also received
      glutamine, and the severe acute pancreatitis group received normal saline. Each
      group was then subdivided into three subgroups of eight rats each, with the rats
      be killed at 12, 24 and 36 h after the operation, respectively. A control group
      underwent sham operation (n = 8). The regional pancreatic microvascular blood
      flow was measured by Doppler ultrasound. The blood flow of the portal vein,
      splenic artery and superior mesenteric artery were also recorded. Apoptosis of
      pancreatic acinar cells was evaluated by TUNEL method. RESULTS: The regional
      pancreatic microvascular blood flow (KHz) decreased significantly in the severe
      acute pancreatitis group (P < 0.01), and continued to decrease after 24 h (vs. 12
      h, P < 0.01). The blood flow of the portal vein, splenic artery and superior
      mesenteric artery also decreased in the severe acute pancreatitis group. The
      glutamine group showed increased regional pancreatic microvascular blood flows,
      as well as increased blood flow of the portal vein, splenic artery and superior
      mesenteric artery (vs. the severe acute pancreatitis group, P < 0.01). The
      apoptotic index of pancreatic acinar in the glutamine group was higher than in
      the severe acute pancreatitis group (P < 0.01), and both were much higher than
      that in the control group (P < 0.01). CONCLUSIONS: Enteral administration of
      glutamine increased the splanchnic blood flow in severe acute pancreatitis rats.
      The apoptotic index of pancreatic acinar was negatively correlated with the
      severity of the disease. The interrelation between glutamine and apoptosis in
      severe acute pancreatitis is worthy of further investigation.

PMID- 16643343
TI  - 'She's manipulative and he's right off': a critical analysis of psychiatric
      nurses' oral and written language in the acute inpatient setting.
AB  - Remarks such as 'she's manipulative' and 'he's right off' are familiar to
      psychiatric nurses. This paper critiques the language nurses use in acute
      inpatient psychiatry services, highlighting the diverse discourses implicated in
      nurses' writing and speaking about patients. Based on a review of the literature,
      this paper examines ethnographic studies and discourse analyses of psychiatric
      nurses' oral and written language. A prominent debate in the literature surrounds
      nurses' use of standardized language, which is the use of set terms for symptoms
      and nursing activities. This review of spoken descriptions of patients highlights
      nurses' use of informal and local descriptions, incorporating elements of moral
      judgement, common sense language and empathy. Research into written accounts in
      patient files and records show nurses' use of objectifying language, the
      dominance of medicine and the emergence of the language of bureaucracy in health
      services. Challenges to the language of psychiatry and psychiatric nursing arise
      from fields as diverse as bioscience, humanism and social theory. Authors who
      focus on the relationship between language, power and the discipline of nursing
      disagree in regard to their analysis of particular language as a constructive
      exercise of power by nurses. Thus, particular language is in some instances
      endorsed and in other instances censured, by nurses in research and practice. In
      this paper, a Foucauldian analysis provides further critique of taken-for-granted
      practices of speech and writing. Rather than censoring language, we recommend
      that nurses, researchers and educators attend to nurses' everyday language and
      explore what it produces for nurses, patients and society.

PMID- 16643344
TI  - Staff gender ratio and aggression in a forensic psychiatric hospital.
AB  - Gender balance in acute psychiatric inpatient units remains a contentious issue.
      In terms of maintaining staff and patient safety, 'balance' is often considered
      by ensuring there are 'sufficient' male nurses present on each shift. In an
      ongoing programme of research into aggression, the authors investigated reported
      incidents of patient aggression and examined the gender ratio on each shift over
      a 6-month period. Contrary to the popular notion that a particular gender ratio
      might have some relationship with the likelihood of aggressive incidents, there
      was no statistically significant difference in the proportion of male staff
      working on the shifts when there was an aggressive incident compared with the
      shifts when there was no aggressive incident. Further, when an incident did
      occur, the severity of the incident bore no relationship with the proportion of
      male staff working on the shift. Nor did the gender of the shift leader have an
      impact on the decision to seclude the patient or the likelihood of completing an
      incident form following an aggressive incident. Staff confidence in managing
      aggression may be influenced by the presence of male staff. Further, aspects of
      prevention and management may be influenced by staff gender. However, results
      suggest there is no evidence that the frequency or severity of aggression is
      influenced by staff gender ratio.

PMID- 16643345
TI  - Verbal and social interactions in Swedish forensic psychiatric nursing care as
      perceived by the patients and nurses.
AB  - Patients and nurses in a Swedish forensic psychiatric unit filled in a
      questionnaire Verbal and Social Interactions designed to survey patients' and
      nurses' views on the frequency and importance of nursing interactions in forensic
      psychiatric care. The patients perceived the 'supportive/encouraging
      interactions' and the 'reality orientation interactions' as the most frequent
      interactions and the 'supportive/encouraging interactions' and the 'social skills
      training' as the most important interactions. The nurses perceived the
      'supportive/encouraging interactions' and the 'practical skills training' as the
      most frequent and the 'supportive/encouraging interactions', 'interpretative
      interactions' and the 'practical skills training' as the most important
      interactions. There were significant differences between patients' and nurses'
      perceptions about the frequency of all the different groups of interactions, but
      greater agreement as to the importance. In general, the patients perceived that
      the interactions occurred less frequently than the nurses. The differences
      between patients' and nurses' perceptions on the interactions as well as the
      clinical implications of these differences are discussed.

PMID- 16643346
TI  - Psychiatric nurses' ethical stance on cigarette smoking by patients: determinants
      and dilemmas in their role in supporting cessation.
AB  - It has been argued that psychiatric nurses are ideally placed to provide smoking
      cessation interventions to patients with mental illness. This assumes that
      psychiatric nurses actively support smoking cessation. The current paper
      articulates some of the reasons why this has not occurred, in particular, some of
      the ethical beliefs held by nurses that may prevent such activity. Such an
      assumption also discounts the evidence that confirms psychiatric nurses to have
      among the highest smoking rates in nursing and in the health professions in
      general. The role and impact of the institution are also considered. In-depth
      interviews with seven community and inpatient psychiatric nurses were
      thematically analysed. Extensive individual and group discussions were also held
      with inpatient nurses from open and locked psychiatric settings during
      participant observation of the settings. The findings suggest that psychiatric
      nurses can be more effective in the primary care role of supporting patients'
      smoking cessation if they receive adequate institutional support to do so.

PMID- 16643347
TI  - A conversation: challenging the relevance and wisdom of separate mental health
      legislation.
AB  - This paper explores the dilemmas encountered by mental health nurses when working
      with mental health legislation. The concerns and considerations of an expert
      mental health nurse, complemented by the opinion of an expert in health-care and
      legal issues are presented. It is argued that there is currently a distorted
      perception with regard to the function and sentiment of mental health
      legislation, and this paper aims to restore balance in interpreting and working
      with such law. Viewing mental health legislation primarily as a mechanism for
      involuntary hospitalization effectively removes any power or recourse given to
      mental health consumers by the law. Principles of mental health care and
      legislation are examined as well as the relationship the law has with
      dangerousness to self or others and mental ill health. A dialogue is established
      between the two authors to assist the exploration of these legal and clinical
      issues. The continued relevance of specific mental health legislation is brought
      into question. It is proposed that the existence of such legislation constitutes
      discrimination and contributes to stigma associated with mental illness. An
      alternative legislation for all circumstances where an individual is deemed
      incompetent is proposed as the most significant step towards mainstreaming of
      mental health care and an end to discrimination.

PMID- 16643348
TI  - Registered nurses as responsible clinicians under the New Zealand Mental Health
      (Compulsory Assessment and Treatment) Act 1992.
AB  - The objectives of this research were to determine how many registered nurses are
      working as 'responsible clinicians', under what phases of the legislation they
      are functioning, and to describe the enabling processes and barriers to nurses
      undertaking this statutory role. An anonymous descriptive survey was distributed
      to the 11 nurses who were currently responsible clinicians as well as five senior
      nurses selected from each of the 21 District Health Boards and the Auckland
      Regional Forensic Psychiatry Services (n = 121). The response rate was 88.4% (n =
      107). The survey questioned respondents on statutory roles currently undertaken.
      Respondents were asked whether the responsible clinician role was a legitimate
      one for nurses and whether they were motivated to attain it. They were also asked
      which competencies of the role they believed they met, their perceptions of
      credentialing processes and the educational requirements needed to achieve the
      role. A descriptive statistical analysis was undertaken and open-ended questions
      were analysed using content analysis. Of the approximately 395 responsible
      clinicians nationally, 11 (2.8%) are nurses. Most nurses viewed the role as
      legitimate. However, many were unaware of competencies for the role and
      credentialing processes, and were somewhat ambivalent about achieving the role
      due to current workload, role conflict and lack of remuneration. Competency
      deficits were highlighted. There are grounds to encourage nurses as responsible
      clinicians given the intent of the legislation. This will require the
      promulgation of appropriate mental health policy, and a concerted effort by major
      stakeholders in mental health service delivery.

PMID- 16643349
TI  - Conflicting agendas between consumers and carers: the perspectives of carers and
      nurses.
AB  - Increasingly, Australian government policy advances an expectation that consumer
      and carer participation will be present in all aspects of mental health service
      delivery. A review of the literature suggests that consumers and carers actively
      seek the opportunity to participate but are frequently hampered by barriers.
      However, government policy documents tend to discuss consumers and carers with
      regards to participation as though their needs and desires are essentially
      similar. This paper presents the findings of a qualitative research project
      involving in-depth interviews with carers and mental health nurses. The issue of
      conflict between the issues for consumers and carers emerged as a major theme.
      This issue is explored and discussed in light of the goals of current mental
      health policy. It is concluded that conflicting agendas are apparent and must be
      addressed if genuine participation in service delivery is possible for both
      consumers and carers.

PMID- 16643350
TI  - Treading lightly: spirituality issues in mental health nursing.
AB  - Spirituality has been recognized as an important part of nursing practice since
      its early beginnings. However, debate continues about whether and how nurses and
      other mental health professionals should include spirituality within their daily
      work. This paper aims to contribute to the discussion of spirituality within
      mental health nursing, through considering findings from a Heideggerian
      phenomenological study conducted with six people with mental illness living in
      regional Australia. This study aimed to provide a greater understanding of the
      phenomenon of spirituality by answering a primary research question, 'What does
      spirituality mean for people with a mental illness?' Participants were
      interviewed and data analysed using an iterative approach. Findings emerged
      through multiple readings and meanings were gradually constructed from the data
      into themes. The themes describe that spirituality is experienced uniquely for
      the participants, and that spirituality became vitally important to them when
      they became mentally unwell. In addition, issues of interest to mental health
      nurses were raised but not completely addressed by the study. The issues relate
      to potential interactions about spirituality between nurses and their patients.
      Although participants wanted to discuss their experiences of spirituality with
      others, they raised concerns about whether their mental health care providers
      would be accepting of their beliefs. Spirituality was deemed to be a highly
      individual phenomenon; it could be experienced as a journey and it was life
      sustaining. For these reasons, it is proposed that mental health professionals
      must be prepared to discuss patients' spiritual needs in the context of their
      health concerns.

PMID- 16643351
TI  - Outcome measures: do they fit with a recovery model?

PMID- 16643352
TI  - Validation of three-dimensional cardiac image integration: use of integrated CT
      image into electroanatomic mapping system to perform catheter ablation of atrial
      fibrillation.
AB  - INTRODUCTION: Accurate visualization of the complex left atrial (LA) anatomy and
      the location of an ablation catheter within the chamber is important in the
      success and safety of ablation for atrial fibrillation (AF). We describe the
      integration of CT into an electroanatomic mapping (EAM) system and its validation
      in patients undergoing catheter ablation for AF. METHODS AND RESULTS: Thirty
      patients (59.2 +/- 8 years, 25 M) with paroxysmal (12) and persistent (18) AF
      underwent ablation using CT image integration into an electroanatomic mapping
      system. CT registration using the pulmonary veins as markers (landmark) was
      achieved with an error of 6.4 +/- 2.8 mm with repeat registration required in two
      patients. Registration of the CT by best fit to a electroanatomic geometry
      (surface) was achieved with an error of 2.3 +/- 0.4 mm. There was no significant
      difference in the regional LA registration error at superior (1.7 +/- 0.7 mm),
      inferior (2.2 +/- 1.4 mm), septal (1.7 +/- 0.8 mm), and lateral (1.7 +/- 0.7 mm,
      P = 0.13) sites. Cardiac rhythm at the time of CT did not have a significant
      effect on total or regional surface registration accuracy (mean total 2.5 +/- 0.3
      in AF patients vs 2.3 +/- 0.5 in SR patients, P = 0.22). The integrated CT was
      used to guide the encirclement of the pulmonary veins (PV) in pairs with
      electrical isolation achieved by maintaining ablation along the ablation line in
      58 of 60 PV pairs. Postprocedural PV angiography did not demonstrate significant
      stenosis. CONCLUSION: CT image integration into an EAM system was successfully
      performed in patients undergoing catheter ablation for AF. With a greater
      appreciation of the complex and variable nature of the PV and LA anatomy this new
      technology may improve the efficacy and safety of the procedure.

PMID- 16643353
TI  - Virtual anatomy for atrial fibrillation ablation.

PMID- 16643354
TI  - The impact of posture on cardiac repolarization: more than heart rate?
AB  - INTRODUCTION: The effect of standing on heart rate and QT is well known but its
      impact on QTc is less clear. METHODS: Serial supine and standing 12-lead ECGs
      (seven pairs each day) were recorded from 54 healthy volunteers each day of a
      three-day period. ECGs were captured digitally and over-read by a cardiologist.
      RESULTS: A statistically significant shortening of RR (216 ms), QT (40 ms), and
      decreases in QTc-F (Fridericia) and QTc-LR (Framingham) were demonstrated on
      standing (8.3 and 6.9 ms, respectively). In contrast, QTc-B (Bazett's)
      significantly increased by 9.6 ms. Two subject-individualized correction methods
      were derived using each subject's supine measurements. Both showed significant
      decreases in QTc of approximately 13-14 ms upon standing. Using the bin analysis
      method, comparisons between positions using 25 ms interval RR bins revealed
      significant QT shortening of up to 15 ms upon standing. CONCLUSION: We have
      demonstrated a postural effect on cardiac repolarization independent of heart
      rate using two individualized correction methods, as well as QTc-F and QTc-LR,
      and the bin method. Characterization of postural differences in QT/QTc (other
      than QTc-B) may provide a safe and inexpensive physiological control to validate
      the ECG methodology used in clinical trials to assess potential drug-induced QT
      interval changes.

PMID- 16643355
TI  - Ablation of nonautomatic focal atrial tachycardia in children and adults with
      congenital heart disease.
AB  - INTRODUCTION: Nonautomatic focal atrial tachycardia (NAFAT) has been
      characterized in adults with structurally normal hearts. This article
      characterizes NAFAT in a population of patients with complex congenital heart
      disease. METHODS AND RESULTS: Electrophysiologic and electroanatomic mapping data
      and acute outcomes were reviewed in patients undergoing mapping and ablative
      procedures for atrial tachycardia at Children's Hospital, Boston, between January
      1999 and December 2003. Twenty-two NAFAT foci were identified in 17 patients out
      of 216 patients studied. Fourteen of these 17 patients had congenital heart
      disease. The average age of the patients with a NAFAT mechanism was 27 years and
      there was no gender predilection. The presumptive diagnosis based on clinical
      grounds and surface ECG assessment in 11 of 17 patients with NAFAT was atrial
      flutter. None of the 17 patients were suspected of having a NAFAT mechanism by
      noninvasive assessment. Four of the 10 patients had both NAFAT and macroreentrant
      atrial tachycardias. NAFAT cycle lengths varied widely (200-680 ms) between
      patients. Sixteen of the 22 NAFAT foci were mapped to the anatomic right atrium
      (RA). Acute ablative success was achieved in 17 out of 22 foci (77%). CONCLUSION:
      NAFAT is relatively uncommon in a pediatric tertiary care setting, and in that
      setting occurs most often in adults with congenital heart disease. NAFAT is
      indistinguishable from other forms of atrial tachycardia by noninvasive means and
      can mimic other forms of atrial tachycardia on electrocardiogram. The foci were
      predominantly found in the RA and were, in most cases, acutely amenable to
      catheter ablation therapy.

PMID- 16643356
TI  - Mechanisms of atrial tachyarrhythmias following surgical atrial fibrillation
      ablation.
AB  - INTRODUCTION: Typical and atypical atrial flutters (AFLs) and atrial tachycardias
      (ATs) have been reported in patients with prior surgical atrial fibrillation
      ablation. The underlying mechanisms for this group of atrial tachyarrhythmias
      have not been well characterized and the efficacy of catheter ablation in their
      treatment is unknown. METHODS AND RESULTS: Twenty patients (6 females) with a
      surface ECG diagnosis of AFL or AT following surgical atrial fibrillation
      ablation underwent 26 electrophysiology studies. Patients manifesting sustained,
      organized, and beat-by-beat reproducible atrial electrical activity underwent
      complete right and left atrial catheter mapping and catheter ablation. One
      patient had no inducible tachyarrhythmia, while 5 patients had nonmappable
      arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were
      completely characterized in 14 patients. The underlying mechanisms were macro
      reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and
      atypical right AFL (n = 1). Of the 19 completely characterized atrial
      arrhythmias, catheter ablation was performed for 18, and the procedure was
      successful for 13 of these. After a mean follow-up of 15 +/- 10 months, 15 of 20
      patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with
      AT/flutter ablation. Ten patients, including 6 following ablation, were
      maintaining sinus rhythm without antiarrhythmic medications. CONCLUSIONS:
      Patients with an ECG diagnosis of AFL or AT following surgical atrial
      fibrillation ablation may have multiple tachycardia mechanisms with the right or
      left atrium as the site of origin. Many of these rhythms may resolve with further
      maturation of surgical atrial fibrillation ablation (SAFA) lesions or be
      treatable with antiarrhythmic medication. However, persistent tachyarrhythmias
      can often be treated successfully with catheter mapping and ablation.

PMID- 16643357
TI  - Atrial tachyarrhythmias after atrial fibrillation ablation procedures: trading
      one tachycardia for another?

PMID- 16643358
TI  - The effect of induction method on defibrillation threshold and ventricular
      fibrillation cycle length.
AB  - INTRODUCTION: Since no clinical data are available on the comparison of the
      "shock on T-wave" and "high frequency burst" ventricular fibrillation (VF)
      induction modes during defibrillation threshold (DFT) testing, we aimed to
      compare these two methods during implantable cardioverter defibrillator
      implantation. METHODS: The DFT was determined with a step-down protocol using
      biphasic, anodal polarity (100%, 40%, 20% voltage control) shocks. Patients were
      randomized: VF was induced by 50 Hz burst in group B (n = 45) and T-wave shock in
      group T (n = 41). The DFT was defined as the lowest energy level that terminated
      VF; confirmed DFT (DFTc) was defined as the minimal energy level that
      consecutively terminated VF twice. Success rate of DFTc was calculated during an
      intraindividual test for the alternate induction method. RESULTS: A total of 546
      episodes of VF were induced: n = 278 (B) vs n = 268 (T). Incidence of VT during
      inductions was 9.9% (B) vs 2.7% (T), P < 0.05. Neither the DFT, 8.8 +/- 4.0 J (B)
      vs 9.7 +/- 4.2 J (T), nor the DFTc, 10.6 +/- 5.1 J (B) vs 10.8 +/- 4.2 J (T),
      proved to be significantly different. A significant correlation was found between
      VF cycle length (CL) and the concomitant DFT (r = 0.298, P < 0.05) in group T
      only. Subgroup analysis of patients under chronic class III antiarrhythmic
      treatment showed no increase of the DFT in either group and significantly lower
      incidence of VT induction in group T regardless of antiarrhythmic treatment.
      CONCLUSION: The DFT and the VFCL proved to be independent of the VF induction
      method. The T-wave shock was more unlikely to induce VT during DFT testing. These
      results suggest that both methods are reliable in DFT determination, though T
      wave shock application is a more reliable method for DFT testing.

PMID- 16643359
TI  - Organization of frequency spectra of atrial fibrillation: relevance to
      radiofrequency catheter ablation.
AB  - INTRODUCTION: We hypothesized that the frequency spectra of fibrillatory
      electrograms may reflect the complexity of activities perpetuating atrial
      fibrillation (AF). To test this hypothesis, we evaluated the frequency spectra in
      patients with paroxysmal AF in relation to catheter ablation. METHODS AND
      RESULTS: This study comprised two protocols: 25 patients undergoing pulmonary
      vein (PV) isolation in protocol I, and 20 patients undergoing mitral isthmus
      linear ablation after PV isolation in protocol II. The mean of dominant frequency
      (DF) and organization index (the ratio of the area under the DF and its harmonics
      to the total power) were determined from 32-second recordings in the coronary
      sinus. In protocol I, a PV was considered "driver" of AF if isolation of the PV
      resulted in termination or slowing of AF (decrease in DF by > or =0.25 Hz).
      Twenty-one patients had AF termination during four PV isolation. Among these 21
      patients, 13 patients with single driving PV showed significantly higher baseline
      organization index than eight patients with multiple driving PVs (0.45 +/- 0.08
      vs 0.35 +/- 0.07, P = 0.009). Patients with multiple driving PVs showed a
      significant increase in the organization index to 0.45 +/- 0.11 (P < 0.05) after
      isolation of the initial driving PVs. In protocol II, the baseline organization
      index was significantly higher in seven patients who had termination of AF during
      mitral isthmus ablation than 13 patients who did not (0.50 +/- 0.10 vs 0.38 +/-
      0.07, P < 0.008). The baseline DF was not associated with outcomes of ablation in
      both protocols. CONCLUSIONS: A higher organization index of atrial electrograms
      is associated with termination of AF during limited ablation. This parameter may
      be useful to anticipate the extent of ablation.

PMID- 16643360
TI  - The spectrum of atrial domestication.

PMID- 16643361
TI  - Decreasing pain and anxiety associated with patient-activated atrial shock: a
      placebo-controlled study of adjunctive sedation with oral triazolam.
AB  - INTRODUCTION: Implantable atrial defibrillators (IADs) have proved to be safe and
      effective in the management of atrial fibrillation. A potential limitation of
      self-activated IAD therapy is patient-reported pain and anxiety. The main
      objective of the present study was to determine whether triazolam improved
      patient perception of the shock experience or altered patient memory of shock
      discomfort relative to placebo. METHODS AND RESULTS: A total of 15 men and women
      (mean age: 59 +/- 6 years) were enrolled in this double-blind, placebo
      controlled, crossover study of triazolam. Randomized study medication was
      administered orally 75 minutes prior to scheduled atrial shock delivery. Patient
      perception of the shock experience was assessed along with sedation, memory,
      anxiety, and mood. Triazolam reduced mean pre-shock anxiety (t= 2.98, df = 14, P
      = 0.01) and shock-related pain (t= 2.74, df = 13, P = 0.01) and intensity (t=
      2.64, df = 13, P = 0.018) relative to placebo. Similarly, participants recalled
      less discomfort the morning after shock with triazolam than with placebo (t=
      2.82, df = 11, P = 0.017). CONCLUSIONS: This study was the first to investigate
      the use of an oral benzodiazepine administered prior to patient-activated shock
      delivery with an IAD. Our data indicate that oral triazolam is beneficial in
      decreasing pain and anxiety associated with self-activated atrial defibrillation.
      If triazolam provides a similar benefit in the community to that which has been
      reported here, this medication could be offered to patients as an adjunct to
      intermittent IAD therapy.

PMID- 16643362
TI  - Increased intra-QRS fragmentation in magnetocardiography as a predictor of
      arrhythmic events and mortality in patients with cardiac dysfunction after
      myocardial infarction.
AB  - INTRODUCTION: Increased intra-QRS fragmentation score (FRA) in
      magnetocardiography (MCG) has shown association with sustained ventricular
      arrhythmias in post-MI patients suggesting its relation to arrhythmia substrate.
      The aim of this study was to investigate whether increased FRA in MCG predicts
      arrhythmic events and mortality after acute myocardial infarction (MI) with
      cardiac dysfunction. METHODS AND RESULTS: A series of 158 patients with acute MI
      and left ventricular ejection fraction (LVEF) <50% were studied. Their age was 60
      +/- 10 years and LVEF 40 +/- 6%. MCG was registered and FRA was computed. For
      comparison, QRS duration in 12-lead ECG was measured. In a mean follow-up of 50
      +/- 15 months, 32 (20%) patients died and 18 (11%) had an arrhythmic event. Both
      arrhythmic event rate and all-cause mortality were significantly higher in
      patients with increased FRA (P < 0.001 for both). In contrast, increased QRS
      duration in ECG predicted all-cause mortality (P < 0.05) but not arrhythmic
      events. In multivariate analysis, FRA was an independent predictor of both
      arrhythmic events and all-cause mortality. Using a combined criterion of
      increased FRA and LVEF < 30% yielded positive and negative predictive accuracies
      of 50% and 91% for arrhythmic events. CONCLUSION: In post-MI patients with left
      ventricular dysfunction, increased intra-QRS fragmentation in high-resolution
      magnetocardiography predicts arrhythmic events, whereas QRS duration in 12-lead
      ECG predicts all-cause mortality. Analysis of intra-QRS fragmentation by MCG may
      assist in guiding therapy of post-MI patients, for example, by selecting those
      who would benefit most from prophylactic implantable cardioverter-defibrillator
      therapy.

PMID- 16643363
TI  - Magnetocardiography throws its hat in the ring.

PMID- 16643364
TI  - Esophageal temperature during radiofrequency-catheter ablation of left atrium: a
      three-dimensional computer modeling study.
AB  - INTRODUCTION: There is current interest in finding a way to minimize thermal
      injury in the esophagus during radiofrequency-catheter ablation of the left
      atrium. Despite the fact that the esophageal temperature is now being monitored
      during ablation, the influence of different anatomic and technical factors on the
      temperature rise remains unknown. METHODS AND RESULTS: We implemented a three
      dimensional computational model that included atrial tissue, epicardial fat,
      esophagus, aorta, and lung, all linked by connective tissue. The finite-element
      method was used to calculate the esophageal temperature distribution during a
      procedure of constant-temperature ablation with an 8-mm electrode, under
      different tissue conditions. Results showed that the distance between electrode
      and esophagus was the most important anatomic factor in predicting the esophageal
      temperature rise, the composition of the different tissues being of lesser
      importance. The measurement of the esophageal temperature in different sites of
      the lumen offered differences up to 3.7 degrees C, especially for a short
      electrode-esophagus distance (5 mm). The difference in the convective cooling by
      circulating blood around electrode and endocardium did not show a significant
      influence on the esophageal temperature rise. CONCLUSION: Computer results
      suggest that (1) the electrode-esophagus distance is the most important anatomic
      factor; (2) the incorrect positioning of an esophageal temperature probe could
      give a low reading for the maximum temperature reached in the esophagus; and (3)
      the different cooling effect of the circulating blood flow at different atrial
      sites has little impact on the esophageal temperature rise.

PMID- 16643365
TI  - Change in size of lesions over 3 weeks after radiofrequency ablation of left
      ventricle.
AB  - INTRODUCTION: The initial success or failure of radiofrequency ablation (RFA)
      does not always reflect the long-term outcome that can lead to complications such
      as late atrioventricular block or recurrence of accessory pathways. We
      hypothesize that these occurrences may be due to a change in lesion size over
      time. METHODS AND RESULTS: Intramural RFAs were performed on five greyhounds at
      thoracotomy using an epicardial approach into the left ventricular (LV) wall.
      Twenty-one gauge needle electrode ablations were created in the anterior aspect
      of the left ventricle. Radiofrequency energy was delivered at 600 Hz for 60
      seconds and at an electrode temperature of 90 degrees C. Eight ablations were
      created in each greyhound and the chest was closed. After 3 weeks, a further
      eight ablations were created under the same conditions in the lateral aspect of
      the LV, ensuring they were well away from the chronic lesions, and the dogs were
      sacrificed an hour later. All lesions were removed, stained with Gomori Trichrome
      and measured. There was no significant difference in lesion size detected in the
      1-hour-old lesions compared with 3-week-old lesions. Acute lesions were well
      demarcated by an area of fibrous scar and a central necrotic region. Chronic
      lesions showed chronic inflammatory cells and strands of collagen. CONCLUSIONS:
      This study shows no change in lesion dimension over time and hence a change in
      size may not contribute to a change in RFA outcome over time.

PMID- 16643366
TI  - Calmodulin antagonist W-7 prevents sparfloxacin-induced early
      afterdepolarizations (EADs) in isolated rabbit purkinje fibers: importance of
      beat-to-beat instability of the repolarization.
AB  - INTRODUCTION: The occurrence of early afterdepolarizations (EADs) has been
      related to the incidence of torsades de pointes in drug-induced long QT (LQT).
      The generation of EADs may be facilitated by Ca(2+)/calmodulin-dependent protein
      kinase II (CaM kinase). METHODS AND RESULTS: In the present study, we
      investigated a possible involvement of Ca(2+)/Calmodulin dependent protein kinase
      in the generation of sparfloxacin-induced EADs in isolated rabbit Purkinje fibers
      by means of a calmodulin antagonist W-7. EADs were evident in 8 of the 10
      preparations perfused with sparfloxacin at 1 x 10(-4) M and stimulated at 0.2 Hz.
      The induction of EADs by sparfloxacin was associated with a large prolongation of
      the duration of the action potential (APD), an increase in the triangulation, and
      the short-term instability of the repolarization. CaM kinase blockade with the
      calmodulin antagonist W-7 inhibited sparfloxacin-induced EADs in a concentration
      dependent manner (EADs were induced in 3 of 10, 1 of 10, and 0 of 8 preparations
      in the presence of W-7 at 5 x 10(-7) M, 5 x 10(-6) M, and 5 x 10(-5) M,
      respectively; P < 0.01 at 5 x 10(-6) M and 5 x 10(-5) M). The inhibition of
      sparfloxacin-induced EADs by W-7 at 5 x 10(-7) M and 5 x 10(-6) M was associated
      with a significant decrease in the beat-to-beat instability but not associated
      with a significant shortening of the APD and reduction of V(max). CONCLUSION: The
      present findings support the hypothesis that CaM kinase may be a proarrhythmic
      signaling molecule and demonstrate that CaM kinase may be involved in the
      generation of EADs in drug-induced LQT and enhanced beat-to-beat instability of
      repolarization is essential for the genesis of EADs in rabbit in vitro.

PMID- 16643367
TI  - Preexisting pulmonary vein stenosis in patients undergoing atrial fibrillation
      ablation: a report of five cases.
AB  - INTRODUCTION: Acquired pulmonary vein (PV) stenosis is a well-known complication
      following catheter ablation of atrial fibrillation (AF). However, the details of
      congenital PV stenosis have not been reported in patients who underwent catheter
      ablation of AF. METHODS AND RESULTS: A total of 178 patients (110 men, age: 54 +/
      11 years) with drug-refractory AF received MRA or multidetector CT (MDCT) before
      ablation for delineation of PV morphologies. Five PVs in 5 patients (2.8%) showed
      at least 50% stenosis before ablation. We demonstrated two types of preexisting
      PV stenosis. Type I is the external compression of PV by the descending aorta,
      observed in LIPV of the three patients. Type II is the focal narrowing of PV,
      observed in RSPV of the two patients. CONCLUSION: Preexisting stenosis of PV may
      be a consequence of congenital focal narrowing or external compression by the
      adjacent structures. Detection of this condition by 3D CT or MRA before catheter
      ablation can provide information for planning of ablation strategy and prevent
      misdiagnosis of ablation-related PV stenosis.

PMID- 16643368
TI  - Catheter ablation of ventricular fibrillation storm in patients with infiltrative
      amyloidosis of the heart.
AB  - Recent studies have demonstrated that premature ventricular contractions (PVCs)
      originating from the Purkinje system are responsible for initiation of
      ventricular fibrillation (VF) in patients with and without structural heart
      disease. Ablation of the PVCs has been shown to be feasible. We report 2 patients
      with repetitive VF associated with cardiac amyloidosis. Each episode of
      ventricular arrhythmia was preceded by monomorphic PVC. The electrical storms
      were drug resistant. Electrophysiological testing was performed and the sites of
      earliest activation were localized within the left ventricle in the absence of
      significant scar tissue. After ablation, PVCs subsided and there were no further
      VF recurrences.

PMID- 16643369
TI  - Fusion of electroanatomical activation maps and multislice computed tomography to
      guide ablation of a focal atrial tachycardia in a fontan patient.
AB  - INTRODUCTION: Ablation of atrial tachycardia (AT) occurring late after cardiac
      surgery for congenital heart disease can be challenging due to the complexity of
      the arrhythmogenic substrate. METHODS AND RESULTS: We performed an ablation
      procedure in a Fontan patient with an AT using a new approach combining 3D
      electroanatomical mapping with multislice computed tomography (MSCT). This
      technique visualizes the position of the catheter in relation to the endocardium,
      thereby improving delineation of scar tissue. The AT had a focal origin located
      between areas of scar tissue and was successfully ablated at the earliest
      activated site. CONCLUSION: Ablation of complex arrhythmias can be facilitated by
      fusion of electroanatomical map and MSCT.

PMID- 16643370
TI  - Temporary esophageal stenting allows healing of esophageal perforations following
      atrial fibrillation ablation procedures.
AB  - BACKGROUND: Left atrial catheter ablation (LACA) has emerged as a successful
      method to eliminate atrial fibrillation (AF). Recent reports have described atrio
      esophageal fistulas, often resulting in death, from this procedure. Temporary
      esophageal stenting is an established therapy for malignant esophageal disease.
      We describe the first case of successful temporary esophageal stenting for an
      esophageal perforation following LACA. CASE: A 48-year-old man with symptomatic
      drug refractory lone AF underwent an uneventful LACA. Fifty-nine ablations with
      an 8-mm tip ablation catheter (30 seconds, 70 Watts, 55 degrees C), as guided by
      3-D NavX mapping, were performed in the left atrium to isolate the pulmonary
      veins as well as a left atrial flutter and roof ablation line. In addition,
      complex atrial electrograms in AF and sites of vagal innervation were ablated.
      Two weeks later, he presented with sub-sternal chest pain, fever, and dysphagia.
      A chest CT showed a 3-mm esophageal perforation at the level of the left atrium
      with mediastinal soiling and no pericardial effusion. An urgent upper endoscopy
      with placement of a PolyFlex removable esophageal stent to seal off the esophago
      mediastinal fistula was performed. After 3 weeks of i.v. antibiotics, naso
      jejunal tube feedings, and esophageal stenting, the perforation resolved and the
      stent was removed. Over 18 months of follow-up, there have been no other
      complications, and he has returned to a physically active life and remains free
      from AF on previously ineffective anti-arrhythmic drugs. CONCLUSION: Early
      diagnosis of esophageal perforations following LACA may allow temporary
      esophageal stenting with successful esophageal healing. Prompt chest CT scans
      with oral and i.v. contrast should be considered in any patient with sub-sternal
      chest pain or dysphagia following LACA.

PMID- 16643371
TI  - The garden path.

PMID- 16643372
TI  - Giant right atrial diverticulum associated with Wolff-Parkinson-White syndrome.

PMID- 16643373
TI  - Suppression of implantable cardioverter defibrillator therapy during magnetic
      resonance imaging.

PMID- 16643374
TI  - Inherited conduction system abnormalities--one group of diseases, many genes.
AB  - The cardiac conduction system can be anatomically, developmentally, and
      molecularly distinguished from the working myocardium. Abnormalities in cardiac
      conduction can occur due to a variety of factors, including developmental and
      congenital defects, acquired injury or ischemia of portions of the conduction
      system, or less commonly due to inherited diseases that alter cardiac conduction
      system function. So called "idiopathic" conduction system degeneration may have
      familial clustering, and therefore is consistent with a hereditary basis. This
      "Molecular Perspectives" will highlight several diverse mechanisms of isolated
      conduction system disease as well as conduction system degeneration associated
      with other cardiac and non-cardiac disorders. The first part of this review
      focuses on channelopathies associated with conduction system disease. Human
      genetic studies have identified mutations in the sodium channel SCN5A gene
      causing tachyarrhythmia disorders, as well as progressive cardiac conduction
      system diseases, or overlapping syndromes. Next, the importance of embryonic
      developmental genes such as homeobox and T-box transcription factors are
      highlighted in conduction system development and function. Conduction system
      diseases associated with multisystem disorders, such as muscular and myotonic
      dystrophies, will be described. Last, a new glycogen storage cardiomyopathy
      associated with ventricular preexcitation and progressive conduction system
      degeneration will be reviewed. There are a myriad of mutations identified in
      genes encoding cardiac transcription factors, ion channels, gap junctions, energy
      metabolism regulators, lamins and other structural proteins. Understanding of the
      molecular and ionic mechanisms underlying cardiac conduction is essential for the
      appreciation of the pathogenesis of conduction abnormalities in structurally
      normal and altered hearts.

PMID- 16643376
TI  - On early afterdepolarization, triggered activity, and defibrillation shock
      failure.

PMID- 16643378
TI  - Delayed defibrillation testing after CRT-D implant--weighing competing risks.

PMID- 16643379
TI  - Cell therapy for cardiovascular disorders: coming of age?

PMID- 16643380
TI  - Regenerative medicine for cardiovascular disorders-new milestones: adult stem
      cells.
AB  - Cardiovascular disorders are the leading causes of mortality and morbidity in the
      developed world. Cell-based modalities have received considerable scientific
      attention over the last decade for their potential use in this clinical arena.
      This review was intended as a brief overview on the subject of therapeutic
      potential of adult stem cells in cardiovascular medicine with basic science
      findings and the current status of clinical applications. The historical
      perspective and basic concepts are reviewed and a description of current
      applications and potential adverse effects in cardiovascular medicine is given.
      Future improvements on cell-based therapies will likely provide remarkable
      improvement in survival and quality of life for millions of patients with
      cardiovascular disorders.

PMID- 16643381
TI  - In vivo recellularization of plain decellularized xenografts with specific cell
      characterization in the systemic circulation: histological and
      immunohistochemical study.
AB  - Decellularized biological scaffolds have been used for the tissue engineering of
      heart valves with good results in the pulmonary circulation. However, little
      information is available on the recellularization of plain decellularized
      biological scaffolds in the systemic circulation. The aim of this study was to
      determine whether plain decellularized xenografts (PDXs) can recellularize with
      specific cell characterization in the systemic circulation. The xenogenic aortic
      valved conduit grafts of rabbits were implanted in the abdominal aorta of dogs
      after decellularization. The grafts were explanted at 4, 12, or 24 weeks after
      implantation for histological, immunohistochemical examination, scanning electron
      microscope, and Western blot analysis. Although the valvular structures were
      completely lost after implantation, supravalvular conduits showed normal shapes
      and endothelialization. The PDXs were repopulated with basic vascular cell
      components in approximate natural proportions without immunological responses.
      The PDXs had been recellularized with specific cell characterization in the
      systemic circulation.

PMID- 16643382
TI  - Cultivation of endothelial progenitor cells on fibrin matrix and layering on
      dacron/polytetrafluoroethylene vascular grafts.
AB  - Completely biological tissue-engineered vascular graft is an upcoming substitute
      for damaged blood vessel, but its clinical use is currently limited due to poor
      mechanical strength. Therefore, at present, polymeric small-diameter vascular
      grafts lined with endothelial cells (ECs) to reduce graft thrombosis may be a
      more viable option. Successful construction of EC-seeded artificial grafts faces
      some challenges such as (i) retention of endothelial lining; and (ii)
      availability of differentiated autologous cells. Biomaterial surfaces that are
      modified by depositing extracellular matrix (ECM) components may stabilize cells
      in the lumen against forces of blood flow. Adult stem cells such as endothelial
      progenitor cells (EPCs) circulate in the blood and they usually attach to the
      exposed matrix at the injured blood vessel site. Depending on the signaling
      capabilities of ECM, cells may differentiate into ECs,, and if a similar
      composition of the matrix is provided in vitro, EPCs isolated from blood might
      get differentiated and thus autologous cells for tissue engineering may be
      obtained. In this in vitro study, ECM scaffold consisting of biomolecules such as
      fibrin, fibronectin, and gelatin along with growth factors is found to have
      supported differentiation of EPC into EC. Further, the ECM precoated on Dacron
      and polytetrafluoroethylene is found to have supported the formation of EC
      monolayer that synthesized nitric oxide, and resisted shear stress. Thus,
      biomimetic fibrin composite is found to be suitable not only to seed cells on
      currently available artificial grafts but also to obtain differentiated EC from
      EPC.

PMID- 16643383
TI  - Time-dependent modulation of alignment and differentiation of smooth muscle cells
      seeded on a porous substrate undergoing cyclic mechanical strain.
AB  - The orientation of cellular alignment in smooth muscle tissue engineering is
      directly related to optimal movement of engineered tissue when it is transplanted
      in vivo. Cyclic mechanical strain has been applied to modulate the alignment,
      proliferation, and differentiation of smooth muscle cells. This study was
      conducted to investigate the effects of cyclic mechanical strain on primary
      cultured myofibroblasts seeded onto three-dimensional polymeric scaffolds, and to
      determine the optimal mechanical treatment time required to produce artificial
      smooth muscle. The cells were primary cultured from rabbit esophageal smooth
      muscle layer, and a self-designed stretching chamber was used to modulate the
      cells on porous polyurethane (PU) scaffolds with 10% strain at a frequency of 1
      Hz. The applied cyclic strain induced cellular alignment. In particular, cellular
      alignment perpendicular to the direction of strain was generated in the condition
      strained over 18 h. In terms of proliferation, the strained groups differed
      significantly from the statically cultured group, but no difference was observed
      between groups that were subjected to straining for different lengths of time.
      Quantitative analysis of alpha-smooth muscle actin (SMA) showed that
      differentiation was significantly promoted at 18 h of strain. Penetration of
      primary cultured cells into the pores of PU scaffolds was shown after cyclic
      strain application, especially in 18 and 24 h of strain. Consequently, it is
      expected that myofibroblast/scaffold hybrids, cyclically strained in the defined
      time course, could be practically applied to organize functional smooth muscle
      tissues having consistent cell alignment and up-regulated SMA.

PMID- 16643384
TI  - Effect of cryopreservation techniques on aortic valve glycosaminoglycans.
AB  - This study was designed to evaluate the effect of cryopreservation on the
      glycosaminoglycan (GAG) content of the aortic allografts. Twenty-one porcine
      aortic valves were obtained. Five aortic roots were immediately analyzed without
      cryopreservation, eight were cryopreserved in closed leaflet position, and eight
      in open leaflet position. The groups were compared in terms of GAG concentration
      and subclass proportion in three different zones including the aortic root wall,
      the commissures, and the leaflets. GAG content at the commissures was
      significantly lower in the closed leaflet group than in the other groups (P =
      0.001). The electrophoretic analysis did not show any significant difference in
      the zonal distribution of GAG classes between groups. Quantitative analysis in
      various aortic valve zones suggests that cryopreservation can alter the GAG
      content. Cryopreservation of the aortic valve in an open leaflet position can
      preserve the matrix more efficiently and might prolong the durability of the
      aortic allograft.

PMID- 16643385
TI  - Regional differences in vein wall dynamics under arterial hemodynamic conditions:
      comparison with arteries.
AB  - Factors that explain the different results among veins, and causes of the
      superior performance of vein grafts for small arterial reconstructions, remain
      unclear. The aim was to compare the biomechanical behavior of veins and arteries
      from different regions and sizes under arterial conditions. In vitro pressure and
      diameter were measured in four different veins and three different ovine
      arteries. A diameter-pressure transfer function was designed, and compliance,
      viscous, and inertial indexes, and viscous energy and buffering function were
      calculated. Regional differences in vein mechanical behavior and energy
      dissipation were found. Veins and arteries vary in mechanical properties and
      buffering, but the differences were lesser when considering the smallest artery.
      The differences among veins' viscosity, compliance, and energy dissipation, but
      not in the buffering capability, could be related to different performances of
      veins when used as arterial grafts. The major biomechanical matching could
      contribute to explain veins with better results in small arteries reconstruction.

PMID- 16643386
TI  - Prometheus versus molecular adsorbents recirculating system: comparison of
      efficiency in two different liver detoxification devices.
AB  - Albumin dialysis by the molecular adsorbents recirculating system (MARS) and by
      fractionated plasma separation, adsorption, and dialysis (Prometheus[PROM])
      represent novel nonbiological liver support systems specifically designed to
      remove albumin-bound substances. Preliminary evidence suggests a favorable impact
      of MARS on the course and outcome of liver failure. This study aimed at comparing
      the detoxification capacity of both devices. For this purpose, we performed a
      retrospective analysis on data prospectively collected in patients with acute-on
      chronic liver failure treated with either the MARS (n = 9) or the PROM (n = 9)
      device on 2-5 consecutive days. Each treatment was performed for at least 5 h at
      identical blood and dialysate flows. Blood clearances were calculated during the
      first treatment session for urea nitrogen, creatinine, total bilirubin, and bile
      acids from paired arterial and venous line samples after 1, 4, and 6 h of
      treatment. Reduction ratios for all single-treatment sessions, and the overall
      treatment phase, were calculated from pretreatment and post-treatment values. For
      all markers but bile acids, the single-treatment as well as the overall treatment
      phase reduction ratios obtained with PROM were significantly higher compared with
      those obtained with MARS. PROM led at all time points to higher clearances for
      all evaluated solutes. Blood clearances of protein-bound substances declined over
      time with MARS, but not with PROM. In conclusion, a significant decline in the
      serum level of water-soluble and protein-bound toxins was achieved with both
      devices. PROM produces higher blood clearances for most toxins, which results in
      higher delivered treatment doses compared with a matching treatment with MARS.

PMID- 16643387
TI  - A modeling study of bilirubin kinetics during Molecular Adsorbent Recirculating
      System sessions.
AB  - This work presents a quantitative description, by means of a mathematical model,
      of bilirubin removal during Molecular Adsorbent Recirculating System sessions.
      The model includes four compartments: two for the patient, and two for the
      albumin circuit. Equations in each compartment express mass preservation, mass
      exchange between compartments, and bilirubin-albumin binding kinetics. Model
      development and validation are based on in vivo data of bilirubin concentration
      acquired in eight sessions at different times during the session. The accuracy of
      the model in reproducing real data is high (error in blood = -0.3 +/- 0.93
      mg/dL), if three parameters, representing the depurative efficacy of the system
      (the dialysance of the blood filter and the initial and final clearance of the
      depurative elements in the albumin circuit), are estimated on each single
      session. However, model accuracy is only slightly deteriorated (error in blood = 
      0.4 +/- 0.99 mg/dL) if a single set of parameters (fixing the three parameters at
      their mean values) is adopted. These results suggest that the model may be used a
      priori (i.e., using a single set of parameters) to achieve a satisfactory
      prediction of the overall bilirubin removal, as well as a posteriori for the
      estimation of device parameters. The latter use may allow the investigation of
      the dependence of these parameters on the operative and clinical conditions, in
      the effort to arrive at a rationalization and optimization of the treatment.

PMID- 16643388
TI  - Physiological control of blood pumps using intrinsic pump parameters: a computer
      simulation study.
AB  - Implantable flow and pressure sensors, used to control rotary blood pumps, are
      unreliable in the long term. It is, therefore, desirable to develop a
      physiological control system that depends only on readily available measurements
      of the intrinsic pump parameters, such as measurements of the pump current,
      voltage, and speed (in revolutions per minute). A previously proposed DeltaP
      control method of ventricular assist devices (VADs) requires the implantation of
      two pressure sensors to measure the pressure difference between the left
      ventricle and aorta. In this article, we propose a model-based method for
      estimating DeltaP, which eliminates the need for implantable pressure sensors.
      The developed estimator consists of the extended Kalman filter in conjunction
      with the Golay-Savitzky filter. The performance of the combined estimator-VAD
      controller system was evaluated in computer simulations for a broad range of
      physical activities and varying cardiac conditions. The results show that there
      was no appreciable performance degradation of the estimator-controller system
      compared to the case when DeltaP is measured directly. The proposed approach
      effectively utilizes a VAD as both a pump and a differential pressure sensor,
      thus eliminating the need for dedicated implantable pressure and flow sensors.
      The simulation results show that different pump designs may not be equally
      effective at playing a dual role of a flow actuator and DeltaP sensor.

PMID- 16643389
TI  - Hemodynamics of a pulsatile left ventricular assist device driven by a
      counterpulsation pump in a mock circulation.
AB  - The BCM (CardialCare, Minneapolis, MN, U.S.A.) is a pusher-plate pulsatile left
      ventricular assist device (LVAD) that is operated by counterpulsation pumps. The
      purpose of this work was to assess the fluid dynamics associated with operating
      the BCM in a mock circulation, and also to examine the similarities between
      hemodynamic parameters produced by this device in vitro and those produced by the
      left ventricle (LV) in vivo. The BCM was connected to a true size silicon rubber
      aorta and operated by an intra-aortic balloon pump. We examined the performance
      of the device at two system pressures (6.5 and 8 kPa); at three heart rates (60,
      80, and 100 bpm); and at three pumping frequencies (1:1, 1:2, 1:3). Pressure and
      flow were measured in the upper descending aorta, and wave intensity analysis was
      used to calculate the peak intensity and energy of the compression and expansion
      waves. Pressure and flow waveforms produced by the BCM LVAD in vitro under
      different loading conditions were similar to those observed in vivo under similar
      loadings. Pusher-plate-type LVADs can produce compression and expansion waves
      similar to those generated by healthy LV in vivo.

PMID- 16643390
TI  - The different mechanisms between late and very late recurrences of atrial
      fibrillation in patients undergoing a repeated catheter ablation.
AB  - INTRODUCTION: The mechanisms of late (<1 year after the ablation) and very late
      (>1 year after the ablation) recurrences of paroxysmal atrial fibrillation (AF)
      after catheter ablation have not been reported. METHODS AND RESULTS: Fifty
      consecutive patients undergoing a repeated electrophysiologic study to
      investigate the recurrence of paroxysmal AF after the first ablation were
      included. Group 1 consisted of 12 patients with very late (26 +/- 13 months) and
      group 2 consisted of 38 patients with late (3 +/- 3 months) recurrence of
      paroxysmal AF. In the baseline study, group 1 had a lower incidence of AF foci
      from the pulmonary veins (PVs) (67% vs 92%, P = 0.048) and a higher incidence of
      AF foci from the right atrium (50% vs 13%, P = 0.014) than group 2. In the
      repeated study, group 1 had a higher incidence of AF foci from the right atrium
      (67% vs 3%, P < 0.001) and a lower incidence of AF foci from the left atrium (50%
      vs 97%, P < 0.001), including a lower incidence of AF foci from the PVs (50% vs
      79%, P = 0.07) and from the left atrial free wall (0% vs 29%, P = 0.046) than
      group 2. Furthermore, most of these AF foci (64% of group 1, 65% of group 2) were
      from the previously targeted foci. CONCLUSION: The right atrial foci played an
      important role in the very late recurrence of AF, whereas the left atrial foci
      (the majority were PVs) were the major origin of the late recurrence of AF after
      the catheter ablation of paroxysmal AF.

PMID- 16643391
TI  - Recurrences of atrial fibrillation after ablation: when will this hydra meet its
      Hercules?

PMID- 16643392
TI  - A randomized comparison of permanent septal versus apical right ventricular
      pacing: short-term results.
AB  - OBJECTIVES: This study compared chronic right ventricular (RV) pacing at the
      septum versus apex. BACKGROUND: Chronic RV apical pacing may be detrimental to
      ventricular function. This randomized, pilot study examined whether, compared
      with apical, permanent septal pacing preserves cardiac function. METHODS:
      Ablation of the atrioventricular junction for permanent AF, followed by
      implantation of a DDDR pacemaker connected to two ventricular leads was performed
      in 28 patients. One lead screwed into the septum and another placed at the apex
      were connected to the atrial and ventricular port, respectively. Septum or apex
      was paced by programming AAIR or VVIR modes, respectively. Patients were randomly
      assigned, 4 months later, to pacing at one site for 3 months, and crossed over to
      the other for 3 months. New York Heart Association class, QRS width and axis,
      left ventricular ejection fraction (LVEF), exercise duration, and peak oxygen
      uptake were measured. Results in patients with LVEF > 45% and < or = 45% were
      compared. RESULTS: Septal pacing was associated with shorter QRS (145 +/- 4 msec
      vs 170 +/- 4 msec, P < 0.01) and normal axis (40 degrees +/- 10 degrees vs -71 +/
      4 degrees , P < 0.01). At 3 months, among patients with baseline LVEF < or =
      45%, LVEF was 42 +/- 5% after septal pacing versus 37 +/- 4% after apical pacing
      (P < 0.001). CONCLUSION: In contrast to RV apical pacing, chronic RV septal
      pacing preserved LVEF in patients with baseline LVEF < or = 45%.

PMID- 16643393
TI  - Electrocardiographic events preceding onset of atrial fibrillation: insights
      gained using an implantable loop recorder.
AB  - INTRODUCTION: Previous reports demonstrate that individual patients may have
      distinctive electrocardiographic patterns preceding atrial fibrillation (AF)
      onset. However, these observations are based on single recordings, and are thus
      limited by their "snapshot" derivation; it is unclear whether patterns observed
      on these recordings are consistent over time. We hypothesized that the use of an
      implantable loop recorder (ILR) would be feasible for serial, long-term
      characterization of electrocardiographic events preceding AF onset. METHODS AND
      RESULTS: An ILR was implanted in 29 patients with AF. Patients were instructed to
      activate the device immediately upon experiencing AF symptoms. Analysis focused
      on the electrocardiographic segment immediately preceding AF; each segment was
      classified as one of six patterns: short/long, normal sinus rhythm, absolute
      sinus bradycardia, relative sinus bradycardia, absolute sinus tachycardia, or
      relative sinus tachycardia. From a total of 318 device activations, 105 AF onsets
      were suitable for analysis, acquired from 21 patients over a mean follow-up
      interval of 7 months. Although AF was frequently triggered by an atrial premature
      beat that emerged during normal sinus rhythm, most patients demonstrated a
      variety of onset patterns. Degeneration of uniform atrial tachycardia to AF was
      rare. Significant delay in device activation relative to AF onset was common, as
      was activation in the absence of AF. CONCLUSIONS: Using the ILR, serial, long
      term characterization of electrocardiographic events preceding AF onset was
      feasible, and typically demonstrated a varied pattern within individuals. There
      was significant incongruity between symptomatic and electrocardiographic AF
      burden. As described here, ILR technology is inadequate for the purpose of
      accurate characterization of AF burden.

PMID- 16643394
TI  - Defibrillation energy requirements in an ICD population receiving cardiac
      resynchronization therapy.
AB  - OBJECTIVES: While defibrillation energy requirements (DERs) have been extensively
      studied in patients receiving conventional defibrillators, the DERs of patients
      receiving cardiac resynchronization therapy with defibrillation capability (CRT
      D) devices have not been well described. The purpose of this analysis was to
      characterize DERs (defined as true threshold or the presence of appropriate
      safety margins) in patients undergoing implant of a CRT-D and to determine
      whether DERs in this population were similar to those reported for patients
      undergoing implantation of conventional defibrillators. METHODS: Data were
      analyzed retrospectively from the VENTAK CHF/CONTAK CD biventricular pacing
      study. An appropriate safety margin of at least 10 J was verified with at least
      two successful conversions with 21 J or less. Multivariate logistic regression
      was performed to determine baseline predictors of failed DER testing. RESULTS: Of
      501 patients enrolled, 444 (89%) had successful DER test outcomes. Of the
      remaining 57 patients, 34 converted with energies > or = 21J, and 23 had their
      testing terminated prematurely or were not tested, primarily due to patient
      condition. Larger left ventricular internal dimension in diastole (P = 0.003) and
      prolonged procedure time (P = 0.01) were significant predictors of higher energy
      requirements. Few significant complications arose from DER testing. CONCLUSIONS:
      DER testing can be accomplished safely and successfully in the majority of CRT-D
      patients. However, safety margins cannot be ascertained in a significant number
      of these patients. Left ventricular inner diameter in diastole (LVIDd) and
      prolonged procedure time may predict higher DERs, and could be used to anticipate
      the need for a high-energy device or inclusion of a subcutaneous array.

PMID- 16643395
TI  - Three-dimensional analysis of pulmonary venous ostial and antral anatomy:
      implications for balloon catheter-based pulmonary vein isolation.
AB  - BACKGROUND: Balloon ablation catheters using various energy sources are being
      developed to perform pulmonary vein (PV) isolation to treat atrial fibrillation.
      Prior evaluations of 2D CT/MR images are limited by the frequent elliptical shape
      of the PV ostia, the nonorthogonal orientation of the PVs to the left atrial (LA)
      chamber, and difficulty in appreciating through-slice curvature. To provide
      anatomical data relevant to balloon catheter ablation, 3D surface reconstructions
      of LA-PVs were generated and analyzed to define ostial architecture and size.
      METHODS AND RESULTS: Using MRI datasets obtained from 101 paroxysmal AF patients,
      the LA-PVs were segmented to generate 3D LA-PV surface reconstructions. Using
      both external and endoluminal projections, the PV ostial and antral regions were
      identified and evaluated. In the left PVs, a common left-sided ostium was
      identified in 94 patients, with an ostial circumference of 95 +/- 15 mm.
      Branching of the left PVs occurred 0-5 mm away from the common left ostium in 43
      patients (43%), 5-15 mm away from the common os in 37 patients (37%), and >15 mm
      away from the common os in 14 patients (14%). In patients with either distinct
      left PV ostia, or common os <15 mm (87 patients), the individual LSPV/LIPV ostial
      circumferences were 67 +/- 12 mm and 58 +/- 9 mm, respectively. Mean left antral
      circumference was 114 +/- 17 mm. In the right PVs, the ostial circumferences of
      the RSPV/RIPV were 68 +/- 11 mm and 66 +/- 11 mm, respectively. Mean right antral
      circumference was 107 +/- 19 mm. Assuming ideal deformation of the LA chamber
      anatomy, the minimal diameters of a balloon ablation catheter required to isolate
      95% of the RSPV, RIPV, LSPV, LIPV, LCPV, left antrum, and right antrum are 29 mm,
      28 mm, 29 mm, 24 mm, 40 mm, 46 mm, and 47 mm, respectively. CONCLUSION: Analysis
      of 3D surface reconstructions of LA-PV anatomy reveals that balloon catheter
      based ablation of the PVs is likely feasible in most patients, but balloon
      ablation of the common PV antra would be problematic.

PMID- 16643396
TI  - Effects of right bundle branch block on the antidromic circus movement
      tachycardia in patients with presumed atriofascicular pathways.
AB  - BACKGROUND: The typical and most common tachycardia in patients with
      atriofascicular pathways is a macro reentrant tachycardia, with anterograde
      conduction over the decrementally conducting bypass tract and retrograde
      conduction over the right bundle branch-His-AV node axis resulting in a short V
      right bundle branch and short V-H interval. OBJECTIVES: To report on changes in
      rate and QRS configuration when right bundle branch block (RBBB) develops
      spontaneously during antidromic tachycardia using an atriofascicular fiber.
      METHODS: Three of 25 patients with an antidromic circus movement tachycardia
      using a right-sided atriofascicular pathway showed episodes of right bundle
      branch block (RBBB) during ventriculo-atrial conduction. Effect of retrograde
      RBBB on tachycardia rate and QRS configuration was studied using intracardiac and
      extracardiac recordings. RESULTS: All 3 patients showed prolongation of their V-A
      interval when retrograde RBBB occurred during tachycardia, resulting in a longer
      tachycardia cycle length. The VA time increase ranged from 85 to 100 msec, with a
      mean 346 +/- 5 msec. Two of the 3 patients also showed a change in QRS
      configuration due to a more leftward shift of the frontal plane QRS axis.
      CONCLUSION: Rate changes in antidromic tachycardia in patients with
      atriofascicular fibers can be based on a shift in VA conduction from one bundle
      branch to the other. This may be accompanied by changes in the frontal plane QRS
      axis because of a change in ventricular activation sequence.

PMID- 16643397
TI  - Atriofascicular pathways: fuzzy nomenclature or merely wishful thinking?

PMID- 16643398
TI  - Anatomic proximity of the esophagus to the coronary sinus: implication for
      catheter ablation within the coronary sinus.
AB  - INTRODUCTION: The anatomic proximity between the esophagus and the coronary sinus
      (CS) might render the esophagus vulnerable to thermal injury during ablation.
      Therefore, we investigated the anatomic relationship between the esophagus and
      the CS in patients with atrial fibrillation (AF). METHODS AND RESULTS: Thirty
      patients (25 males, mean age = 54 +/- 11 years) with drug-refractory paroxysmal
      AF were included. Sixteen-slice multidetector computed tomography was performed
      to depict the course of the esophagus and relationship to the CS. The esophagus
      was in direct contact with the CS in 57% (17/30) of patients (group 1). The mean
      length of the contact was 6.1 +/- 3.4 mm. In the remaining 13 patients, the
      esophagus did not come in direct contact with the CS (group 2). The shortest
      distance between the esophagus and the CS was 4.0 +/- 2.6 mm. The CS diameter
      (9.4 +/- 1.8 vs 8.5 +/- 2.4 mm, P = 0.15), esophagus width (18.6 +/- 1.6 vs 18.6
      +/- 1.7 mm, P = 0.87), anteroposterior diameter of the left atrium (35.9 +/- 3.8
      vs 35.0 +/- 3.3 mm, P = 0.58), thickness of the anterior wall of the esophagus
      (2.9 +/- 0.6 vs 2.9 +/- 0.6 mm, P = 0.97), and shortest distance from the
      esophagus to the CS ostium (19.3 +/- 5.4 vs 25.0 +/- 6.2 mm, P = 0.02) and to the
      great cardiac vein (8.5 +/- 5.3 vs 12.1 +/- 6.9 mm, P = 0.10) were compared
      between the two groups. CONCLUSIONS: In 57% of our patients, the esophagus was in
      direct contact with the CS, and a significantly shorter distance between the
      esophagus and the CS ostium was noted in these patients. It is important to
      prevent esophageal damage when applying energy within the CS.

PMID- 16643399
TI  - Progressive cardiac conduction defect is the prevailing phenotype in carriers of
      a Brugada syndrome SCN5A mutation.
AB  - INTRODUCTION: Loss-of-function mutations in the SCN5A gene encoding the cardiac
      sodium channel are responsible for Brugada syndrome (BS) and also for progressive
      cardiac conduction disease (inherited Lenegre disease). In an attempt to clarify
      the frontier between these two entities, we have characterized cardiac conduction
      defect and its evolution with aging in a cohort of 78 patients carrying a SCN5A
      mutation linked to Brugada syndrome. METHODS AND RESULTS: Families were included
      in the study if a SCN5A mutation was identified in a BS proband and if at least
      two family members were mutation carriers. Sixteen families met the study
      criteria, representing 78 carriers. Resting ECG showed a spontaneous BS ECG
      pattern in 28 of 78 (36%) gene carriers. Intraventricular conduction anomalies
      were identified in 59 of 78 gene carriers including complete (17) or incomplete
      (24) right bundle branch block, right bundle branch block plus hemiblock (6),
      left bundle branch block (1), hemiblock (1), and parietal block (10). PR and QRS
      duration were longer in the gene carrier cohort in comparison with their
      relatives carrying no mutation. Finally, in the gene carrier cohort conduction
      defect progressively aggravated with aging leading in five occasions to pacemaker
      implantations. CONCLUSION: The present study shows that the most common phenotype
      of gene carriers of a BS-type SCN5A mutation is progressive cardiac conduction
      defects similar to the Lenegre disease phenotype. In consequence, we propose that
      carriers of a SCN5A mutation need a clinical and ECG follow-up because of the
      risk associated with severe conduction defects.

PMID- 16643400
TI  - Does an overlap syndrome really exist between Brugada syndrome and progressive
      cardiac conduction defect (Lenegre syndrome)?

PMID- 16643401
TI  - Flutter localized to the anterior left atrium after catheter ablation of atrial
      fibrillation.
AB  - INTRODUCTION: Organized atrial arrhythmias following atrial fibrillation (AF)
      ablation are typically due to recovered pulmonary vein (PV) conduction or reentry
      at incomplete ablation lines. We describe the role of nonablated anterior left
      atrium (LA) in arrhythmias observed after AF ablation. METHODS: A total of 275
      consecutive patients with paroxysmal (n = 200) or chronic (n = 75) AF had PV
      isolation with/without additional linear ablation at the mitral isthmus (n =
      106), LA roof (n = 23), or both (n = 88). Organized arrhythmias occurring after
      ablation were evaluated utilizing activation and entrainment mapping. RESULTS:
      Fourteen patients (11 female, 65 +/- 13 years, 10 chronic AF, 10 structural heart
      disease) demonstrated tachycardia localized to the anterior LA, an area not
      targeted by prior ablation. Eight had ECG features during sinus rhythm suggestive
      of impaired anterior LA conduction at baseline. These arrhythmias demonstrated a
      distinctive ECG flutter morphology in 7 of 10 (70%) with discrete -/+ or +/-/+
      aspect in inferior leads. Mapping the anterior LA revealed electrograms spanning
      the entire tachycardia cycle length (325 +/- 125 msec). Entrainment was possible
      in all with a postpacing interval exceeding the tachycardia cycle length by 9 +/-
      10 msec. Electroanatomic mapping in 6 demonstrated small reentrant circuits
      rotating clockwise in 4 and counterclockwise in 2. Low-amplitude, fractionated
      mid-diastolic potentials with long duration (200 +/- 80 msec) occupying 63 +/-
      22% of the cycle length were targeted for ablation resulting in termination and
      subsequent noninducibility. CONCLUSION: Organized arrhythmias occurring after AF
      ablation can be due to reentrant circuits localized to the anterior LA,
      predominantly in females with chronic AF, structural heart disease, and abnormal
      atrial conduction. They are characterized by a distinctive surface ECG and highly
      responsive to RF ablation at the slow conduction area.

PMID- 16643402
TI  - Hemodynamics and autonomic control of heart rate turbulence.
AB  - INTRODUCTION: Late heart rate deceleration parallels the increase of systolic
      blood pressure during heart rate turbulence (HRT) after ventricular premature
      complexes (VPC). This is consistent with the involvement of baroreflex mechanism.
      Physiological background of systolic blood pressure dynamics is not known.
      Enhanced sympathetic activation and nonautonomic post-VPC changes of stroke
      volume have been speculated on. METHODS AND RESULTS: We studied 28 subjects (aged
      56 +/- 11 years; 20 males; 18 normal and 10 abnormal left ventricular (LV)
      function) with spontaneous occurrence of VPCs. HRT indices and baroreflex
      sensitivity were analyzed from the ECGs and finger arterial pressure recordings
      during 30 minutes of spontaneous respiration in supine position. Beat-by-beat
      stroke volume and peripheral vascular resistance were computed by a nonlinear,
      self-adaptive model of aortic input impedance (Modelflow, Finapres Medical
      Systems, Arnhem, The Netherlands). Indices of HRT and baroreflex sensitivity were
      highly correlated. In patients with preserved LV function, there was no
      substantial dynamics of stroke volume in the late phase after VPC, while
      peripheral vascular resistance increased significantly. In patients with impaired
      LV function, potentiated first sinus beat after VPC triggered transient
      hemodynamic alternans. Dynamics of peripheral vascular resistance was attenuated
      and stroke volume was depressed in the late phase after VPC. CONCLUSIONS: Delayed
      sympathetically mediated vasomotor response to VPC produces systolic blood
      pressure overshoot. This subsequently induces vagally mediated late heart rate
      deceleration. Under physiologic conditions, there is no evidence of other
      hemodynamic and/or mechanical effect outside the autonomic reflex arch. In
      patients with LV dysfunction, both depressed vagal and sympathetic modulation
      and, indirectly, enhanced postextrasystolic potentiation account for attenuated
      HRT.

PMID- 16643403
TI  - Effects of sildenafil citrate on defibrillation efficacy.
AB  - INTRODUCTION: Although fatal arrhythmia and sudden death have been reported in
      patients taking sildenafil citrate, its effect on defibrillation efficacy has not
      been investigated. The aim of this study was to test the hypothesis that
      sildenafil citrate increases the shock strength required to successfully
      defibrillate during ventricular fibrillation (VF). METHODS AND RESULTS: A total
      of 26 pigs (20-25 kg) were randomly assigned into three groups. In each group,
      the defibrillation threshold (DFT) was determined at the beginning of the study
      using a three-reversal up/down protocol. Each shock (RV-SVC, biphasic) was
      delivered after 10 seconds of VF. Group 1 (n = 10) received 50 mg and group 2 (n
      = 10) received 100 mg of sildenafil citrate intravenously at a rate of 2
      mL/minute for 50 minutes. Group 3 (n = 6) received 100 mL of saline intravenously
      at the same rate as in group 1. The DFT was determined again after the drug (drug
      DFT) and saline (saline-DFT) administration. For 100-mg sildenafil citrate
      infusion, the DFT (483 +/- 39 V, 18 +/- 3 J) was significantly (P < 0.003 and P <
      0.01, respectively) higher than the control-DFT (407 +/- 123 V, 13 +/- 7 J). This
      sildenafil citrate infusion increased the DFT approximately 19% by voltage, and
      approximately 38% by total energy. After 50-mg sildenafil citrate infusion, the
      DFT (454 +/- 28 V, 15 +/- 2 J) was not different than the control DFT (449 +/- 28
      V, 15 +/- 2 J). Saline infusion (391 +/- 18 V, 12 +/- 1 J) did not alter the
      control DFT (399 +/- 22 V, 12 +/- 1 J). CONCLUSION: The 100-mg sildenafil citrate
      infusion, representing a supra-therapeutic plasma level, significantly increased
      the DFT. This finding indicates that VF occurring during supra-therapeutic
      sildenafil citrate treatment would require a stronger shock to successfully
      defibrillate.

PMID- 16643404
TI  - "Doctor, why didn't you tell me about this before the ICD?".

PMID- 16643405
TI  - Transient-outward K+ channel inhibition facilitates L-type Ca2+ current in heart.
AB  - BACKGROUND: Transient outward current (I(to)) and L-type calcium current (I(Ca))
      are important repolarization currents in cardiac myocytes. These two currents
      often undergo disease-related remodeling while other currents are spared,
      suggesting a functional coupling between them. Here, we investigated the effects
      of I(to) channel blockers, 4-aminopyridine (4-AP) and heteropodatoxin-2 (HpTx2),
      on I(Ca) in cardiac ventricular myocytes. METHODS AND RESULTS: I(Ca) was recorded
      in enzymatically dissociated mouse and guinea pig ventricular myocytes using the
      whole-cell voltage clamp method. In mouse ventricular myocytes, 4-AP (2 mM)
      significantly facilitated I(Ca) by increasing current amplitude and slowing
      inactivation. These effects were not voltage-dependent. Similar facilitating
      effects were seen when equimolar Ba2+ was substituted for external Ca2+,
      indicating that Ca2+ influx is not required. Measurements of Ca2+/calmodulin
      dependent protein kinase (CaMKII) activity revealed significant increases in
      cells treated with 4-AP. Pretreatment of cells with 10 microM KN93, a specific
      inhibitor of CaMKII, abolished the effects of 4-AP on I(Ca.) To test the
      requirement of I(to), we studied guinea pig ventricular myocytes, which do not
      express I(to) channels. In these cells, 2 mM 4-AP had no effect on I(Ca)
      amplitude or kinetics. In both cell types, Ca2+-induced I(Ca) facilitation, a
      CaMKII-dependent process, was observed. However, 4-AP abolished Ca2+-induced
      I(Ca) facilitation exclusively in mouse ventricular myocytes. CONCLUSION: 4-AP,
      an I(to) blocker, facilitates L-type Ca2+ current through a mechanism involving
      the I(to) channel and CaMKII activation. These data indicate a functional
      association of I(Ca) and I(to) in cardiac myocytes.

PMID- 16643406
TI  - Do intramural virtual electrodes facilitate successful defibrillation? Model
      based analysis of experimental evidence.
AB  - INTRODUCTION: Recent computer model and experimental studies have suggested that
      microscopic intramural collagenous planes may facilitate successful
      defibrillation through the generation of shock-induced virtual electrodes deep
      within the ventricular wall. Evidence supporting the existence of intramural
      virtual electrodes has been drawn from several recent studies, which map shock
      induced membrane potential (Vm) over the cut transmural surface of dissected
      segments of porcine left ventricle (LV). The artificially created transmural
      boundary in these experiments is impermeable to intracellular current. It is not
      known how this constraint limits the interpretation of these experiments in terms
      of the shock response of the intact ventricle. METHODS AND RESULTS: This study
      uses a realistic 3D computer model of LV myocardium to aid experimental
      interpretation. The model incorporates a microstructural description of
      intramural cleavage plane discontinuities measured by confocal microscopy of rat
      LV. Electrical shocks are applied across the model tissue, with and without
      introduced transmural boundaries. Shocks of varying strength (4-40 V/cm) are also
      applied to the model and the response analyzed. Results show that shock-induced
      Vm changes (deltaVm) on a transmural tissue boundary are significantly different
      to deltaVm of the intact ventricle, and the extent of difference depends on
      boundary orientation. However, the presence and qualitative behavior of
      intramural virtual electrodes is preserved irrespective of boundary placement.
      The model also confirms experimental observations that most rapid transmural
      activation occurs for shocks of strength 5-10 V/cm. Two distinct mechanisms
      suppress virtual electrode propagation, and hence slow tissue activation, outside
      of this optimal shock strength range. CONCLUSIONS: This study supports the
      hypothesis that distributed microscopic intramural virtual electrodes contribute
      to rapid activation of the ventricular wall during defibrillation.

PMID- 16643407
TI  - Reentrant and nonreentrant forms of atrio-ventricular nodal tachycardia mimicking
      atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) manifests disorganized atrial activity and
      irregular R-R intervals on electrocardiogram (ECG). Variation in R-R intervals
      can also be seen with other supraventricular tachycardias that may mimic AF.
      OBJECTIVE: We report our observations on three patients who were referred to our
      center to undergo pulmonary vein (PV) isolation for erroneously diagnosed AF in
      the setting of dual atrio-ventricular (AV) nodal pathways manifesting as AV nodal
      reentrant tachycardia (AVNRT) and/or double response during sinus rhythm. METHODS
      AND RESULTS: These three subjects (two females) were derived from a group of 456
      consecutive patients undergoing AF ablation at our center over a 3-year period.
      All three patients had been symptomatic for over 2 years, having failed two or
      more antiarrhythmic medications. In each case AF was initially diagnosed on ECG
      and/or recordings from ambulatory monitoring. However, in all three cases the
      correct diagnosis was established during the invasive electrophysiologic study.
      In one patient during the stimulation protocol, two narrow complex tachycardias
      were serially induced (cycle lengths: 305 and 360 msecs; VA time: 60 and 240
      msecs). The latter was confirmed to be atypical AVNRT and during this
      tachycardia, block in upper pathway was observed. In the other two patients,
      sinus rhythm with repetitive runs of double response and isolated junctional
      beats were observed in the absence of retrograde conduction. Successful slow
      pathway modification was performed in each subject and all three patients have
      remained arrhythmia free over a mean follow-up of 31 +/- 16 months off
      antiarrhythmic medications. CONCLUSIONS: AF can be erroneously diagnosed in
      patients with dual AV nodal pathways manifesting double response and/or AVNRT.
      Incorporating a stimulation protocol as a part of the AF ablation procedure may
      help in diagnosing these rare clinical presentations that can be cured by slow
      pathway modification alone.

PMID- 16643408
TI  - Use of a coronary sinus lead and biventricular ICD to correct a sensing
      abnormality in a patient with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy.
AB  - Implantable cardioverter defibrillators (ICDs) are frequently offered to patients
      with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Yet ICDs
      in these patients may be complicated by poor sensed amplitudes resulting from
      fatty and fibrous tissue replacement of right ventricular myocardium. We present
      the case of a patient with ARVD/C who had inappropriate detection of ventricular
      tachycardia with a single-chamber ICD due to poor sensed right ventricular
      amplitudes. We discuss how the use of a bipolar coronary sinus lead and a
      biventricular ICD generator with a novel header configuration solved the problem.

PMID- 16643409
TI  - Substrate in the interventricular septum for left ventricular and right
      ventricular outflow tract tachycardia: ablation from the right side of the
      septum.
AB  - Simultaneous epicardial and endocardial mapping demonstrated that in a
      substantial number of ventricular tachycardias (VTs) endocardial, intramural, and
      epicardial structures are involved in the substrate of the reentrant circuits.
      Both right and left ventricular breakthrough has also been described during VT
      originating in the interventricular septum. We report the case of a patient with
      a nonischemic left ventricular aneurysm presenting with a left ventricular
      outflow tract (LVOT) tachycardia and a right ventricular outflow tract (RVOT)
      tachycardia. Mapping from the anterior interventricular vein and the endocardium
      of the RVOT revealed mid-diastolic potentials at the epicardium of the LVOT and
      the endocardium of RVOT, where the criteria of central isthmus sites could be
      demonstrated. Ablation targeting an isolated late potential during sinus rhythm
      in RVOT eliminated both the LVOT tachycardia and the RVOT tachycardia. In this
      patient with a nonischemic left ventricular aneurysm, the substrate of a LVOT
      tachycardia and RVOT tachycardia is described, and successful catheter ablation
      of the right and left ventricular tachycardia from the septal wall of RVOT is
      reported.

PMID- 16643410
TI  - Cardioinhibition secondary to ventricular pacing.

PMID- 16643411
TI  - Consecutive blocked paced atrial complexes in a patient with recurrent syncope:
      what is the mechanism?

PMID- 16643412
TI  - Vagaries of the vagus nerve: relevance to ablationists.

PMID- 16643413
TI  - Drug-induced T wave alternans.

PMID- 16643414
TI  - QT interval: how to measure it and what is "normal".

PMID- 16643415
TI  - Thorough QT/QTc not so thorough: removes torsadogenic predictors from the T-wave,
      incriminates safe drugs, and misses profibrillatory drugs.
AB  - Drug-induced QT prolongation has such a strong correlation with torsade de
      pointes (TdP) that it comes to serve as a surrogate for TdP. As a result, drugs
      that prolong QT by as little as a few ms, even without any evidence of TdP, may
      get dropped from development or blocked from approval. However, measurement of QT
      with ms accuracy may be impossible to achieve. Worse, some drugs that lengthen
      the QT interval are not only not proarrhythmic, they may even be antiarrhythmic;
      while some that shorten the QT can be strongly proarrhythmic. Indeed,
      proarrhythmia related to repolarization disturbances is caused by triangulation,
      reverse use dependence, instability, and dispersion (TRIaD). When TRIaD is
      present with QT prolongation it commonly yields TdP, but when TRIaD is combined
      with QT shortening it preferentially leads to VF instead. While TdP is lethal in
      less than 20% of instances, VF is much more morbid. Worse, available evidence
      suggests that there is more death from drug-induced fibrillation than TdP. Thus,
      QT prolongation alone is not very useful. Instead, the T-wave should be used in
      alternate ways: extraction of TRIaD.

PMID- 16643417
TI  - Dispelling the myth: appropriate use of poly-L-lactic acid and clinical
      considerations.
AB  - OBJECTIVES: Injectable poly-L-lactic acid (PLLA; Sculptra) is widely used
      throughout Europe and the USA to restore volume in depressed areas of the face by
      stimulating neocollagenesis. Injectable PLLA was previously marketed as New-Fill,
      which was often injected incorrectly and at too high a concentration, resulting
      in some physicians losing confidence in this product. Today, Sculptra is still
      regarded with a degree of scepticism by some physicians, due to direct or
      indirect experience with New-Fill. Sculptra, both in formulation and use, is
      vastly superior to New-Fill and clinical experience with this product dispels the
      myths associated with the earlier types of injectable PLLA. RESULTS: PLLA is a
      very safe, biodegradable compound that has been used in a wide range of medical
      devices for the last 30 years. In injectable form a good safety profile has been
      proven; however, when the device is overconcentrated, localized overstimulation
      of the fibroblasts can result in the formation of small lumps (subcutaneous
      papules), which are non-pathological but nevertheless palpable by the patient.
      Physicians must also be trained in the injection of this device, as incorrect
      injection technique can cause device-related adverse events. CONCLUSION: New
      product guidelines have ensured that problems with PLLA concentration have been
      countered, and tried and tested injection techniques have been shown to
      ameliorate device-related adverse events, both of which are dispelling the myths
      associated with modern injectable PLLA.

PMID- 16643418
TI  - Facial assessments: identifying the suitable pathway to facial rejuvenation.
AB  - OBJECTIVES: There are now numerous ways in which a patient can rejuvenate their
      facial appearance, including various types of expensive, invasive, surgical
      procedures, and an ever increasing gamut of products that can be inserted or
      injected beneath the skin to restore a youthful look to the face. The importance
      of facial assessments in identifying the most suitable treatment option is
      discussed here. RESULTS: Before a patient commits to any one of these corrective
      options, it is the responsibility of the physician to conduct a thorough
      assessment of the patient's face. All of the facial characteristics should be
      examined closely: underlying bone and musculature, shape, proportion, and
      features including folds, wrinkles, fine lines, volume deficits and changes in
      pigmentation. The degree of ptosis in the facial tissues should be assessed by
      light palpation. Following assessment of the face, digital photographs should be
      taken of the patient's full face and profile, allowing the physician to indicate
      areas, on a visual display, that need correction and there are now computer
      programs which can 'morph' the features of a facial photograph, providing an
      approximation of the post-treatment result. Shape and proportion are neglected
      facets in the assessment of the face prior to corrective treatment. A treatment
      or technique which rejuvenates a 'thin' face may not work so successfully on a
      'round' face and vice versa. Most importantly, the physician should aim to
      understand the patient's objective and subjective perceptions of their face and
      ascertain the results that are desired by the patient before evaluating what can
      be achieved. Appropriate corrective options can then be discussed in detail,
      highlighting the risks, side effects, costs, invasiveness, logistics and
      anticipated outcomes of each. CONCLUSION: A comprehensive assessment of the
      patient's face allows the physician to formulate a regimen of treatments that
      will reach or exceed the expectations of the patient.

PMID- 16643419
TI  - A new option for volumetric restoration: poly-L-lactic acid.
AB  - OBJECTIVES: The market for products and techniques that correct the visible signs
      of facial ageing is now huge. There is a diversity of devices and treatments now
      vying for a share of this growing marketplace, including polymer implants and
      injectable preparations that are based on an array of substances. The vast
      majority of these devices can only provide temporary correction of superficial
      lines and wrinkles, with volumetric augmentation being beyond their capabilities.
      The products and procedures suitable for the restoration of facial volume are
      discussed here. RESULTS: The restoration of facial volume has long been neglected
      in cosmetic rejuvenation as surgical procedures increase skin tension but do
      nothing to restore the underlying facial volume, which is a subtle yet important
      characteristic of the youthful face. Fortunately, devices are now available which
      can augment facial volume for long periods of time or even permanently. These
      include implants based on expanded polytetrafluoroethylene and silicone rubber,
      which provide permanent restoration of volume, but require invasive surgery and
      do not age with the surrounding tissues eventually resulting in an unnatural
      appearance. The cosmetic rejuvenation market now abounds with various injectable
      devices, including: poly-L-lactic acid (PLLA), polymethylmethacrylate, collagens,
      hyaluronic acids, silicone and calcium hydroxylapatite. The choice of which one
      to use in practice is physician led, based on facial assessments, product
      characteristics and the desires of the patient. CONCLUSION: Although there is a
      wealth of products available, injectable PLLA (Sculptra) can restore volume to
      the face providing a natural look. Not only are the results of volume
      augmentation using this device long lasting, but they are also safe.

PMID- 16643420
TI  - Poly-L-lactic acid: consultation on the injection techniques.
AB  - OBJECTIVES: When poly-L-lactic acid (PLLA) was first introduced (marketed as New
      Fill), incorrect injection technique was largely responsible for the
      manifestation of device-related adverse events in the form of subcutaneous
      papules and areas of induration. Now marketed as Sculptra, widespread clinical
      experience with injectable PLLA has resulted in a wealth of information on
      product reconstitution and correct injection technique. The injection techniques
      for the optimal use of injectable PLLA are detailed here. RESULTS: When injecting
      PLLA it is important to adhere to the product guidelines in terms of injection
      volume, depth and placement. As the material provides a gradual restoration of
      volume, PLLA should be injected conservatively, avoiding the possibility of
      overcorrection. Injections should be sufficiently deep to avoid areas of
      induration in the superficial layers of the dermis. Areas above hypermobile
      muscles should also be avoided to prevent localized coalescence of injected
      material. While utilization of a specific injection technique depends on the
      position and severity of the volume deficiency, all injections use a 26-gauge
      needle and are separated by 0.5-1.0 cm. In the lower face a 'criss-cross' and
      'tunnelling' technique should be employed, depositing the material into the deep
      dermis at the junction with the hypodermis, followed by massage every 3-4
      injections. Massage should be continued by the patient for at least a week
      following the treatment session. The 'criss-cross' and 'tunnelling' procedures
      involve the deposition of 0.1-0.2 mL of PLLA per injection. Material injected
      into the temple area should be deposited deep next to the bone with a 'depot'
      technique. Injections around the orbits or perioral region are possible, but
      should not be attempted without sufficient training. CONCLUSION: Adhering to the
      correct injection technique enables the physician to provide durable, natural
      looking volume restoration with a very low incidence of device-related adverse
      events.

PMID- 16643422
TI  - Diffuse bowel fluorodeoxyglucose uptake on positron emission tomography scan
      following allogeneic stem cell transplant.

PMID- 16643423
TI  - A case of orbital malt lymphoma with breast involvement detected by 18FDG
      positron emission tomography.

PMID- 16643424
TI  - Bruising and bleeding in infants and children--a practical approach.
AB  - Bruising and bleeding are commonly seen in children and are usually associated
      with minor injury and trauma. However, in two groups of children the bruising may
      be more significant than expected: those with an underlying haemostatic
      abnormality, such as an inherited bleeding disorder, or those who have been
      subjected to non-accidental injury (NAI). Diagnosing inherited bleeding disorders
      in children is fraught with difficulty, from venous access to interpretation of
      results; the possibility of NAI should be borne in mind, even in those children
      with proven significant bleeding disorders when the severity of the injury and
      the history are non-compatible. We describe the investigation of the haemostatic
      system in children with bruising and/or bleeding with emphasis on the key
      haemostatic disorders that need to be excluded.

PMID- 16643425
TI  - Can haematological tests predict cardiovascular risk? The 2005 Kettle Lecture.
AB  - The risk of venous or arterial thrombosis is routinely assessed by clinical
      variables (risk factors) supplemented by measurement of blood lipids and glucose
      for arterial thrombotic events. Haematological tests that might play a role in
      risk prediction include haemostatic variables, haematocrit and inflammatory
      markers (erythrocyte sedimentation rate, plasma viscosity, white cell count).
      Recent epidemiological studies of these phenotypes and related genotypes are
      reviewed. For the risk prediction of first venous thrombosis, screening for
      thrombophilias in 'high-risk' situations does not appear clinically effective or
      cost-effective; with the possible exception of women considering oral hormone
      replacement therapy. General screening after a first venous event to predict
      recurrence (or risk in asymptomatic relatives) does not appear effective; with
      the possible exception of d-dimer, which requires further study. For risk
      prediction of first arterial thrombosis, screening adds little to prediction by
      current clinical risk scores. Screening of persons after a first arterial event,
      or with atrial fibrillation (e.g. with D-dimer for stroke prediction), requires
      further study. In conclusion, haematological tests have very limited roles in the
      prediction of cardiovascular risk, and should only be used according to evidence
      based guidelines. The need for management studies is highlighted.

PMID- 16643426
TI  - Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet.
AB  - Max Schultze published the first accurate and convincing description of platelets
      as part of a study devoted mainly to the white blood cells in 1865. He recognised
      them as a normal constituent of the blood and 'enthusiastically recommended' them
      as an object for further study by 'those concerned with the in-depth study of the
      blood of humans'. In 1882, Bizzozero demonstrated the value of this
      recommendation in his much more comprehensive study. He observed them
      microscopically in the circulating blood of living animals and in the blood
      removed from the blood vessels. In well-planned experiments, he showed that they
      were the first component of the blood to adhere to damaged blood vessel walls in
      vivo and, in vitro, that they were the first components of the blood to adhere to
      threads that subsequently became covered with fibrin.

PMID- 16643427
TI  - The management of heparin-induced thrombocytopenia.
AB  - The Haemostasis and Thrombosis Task Force of the British Committee for Standards
      in Haematology has produced a concise practical guideline to highlight the key
      issues in the management of heparin-induced thrombocytopenia (HIT) for the
      practicing physician in the UK. The guideline is evidence-based and levels of
      evidence are included in the body of the article. All patients who are to receive
      heparin of any sort should have a platelet count on the day of starting
      treatment. For patients who have been exposed to heparin in the last 100 d, a
      baseline platelet count and a platelet count 24 h after starting heparin should
      be obtained. For all patients receiving unfractionated heparin (UFH), alternate
      day platelet counts should be performed from days 4 to 14. For surgical and
      medical patients receiving low-molecular-weight heparin (LMWH) platelet counts
      should be performed every 2-4 d from days 4 to 14. Obstetric patients receiving
      treatment doses of LMWH should have platelet counts performed every 2-4 d from
      days 4 to 14. Obstetric patients receiving prophylactic LMWH are at low risk and
      do not need routine platelet monitoring. If the platelet count falls by 50% or
      more, or falls below the laboratory normal range and/or the patient develops new
      thrombosis or skin allergy between days 4 and 14 of heparin administration HIT
      should be considered and a clinical assessment made. If the pretest probability
      of HIT is high, heparin should be stopped and an alternative anticoagulant
      started at full dosage unless there are significant contraindications while
      laboratory tests are performed. Platelet activation assays using washed platelets
      have a higher sensitivity than platelet aggregation assays but are technically
      demanding and their use should be restricted to laboratories experienced in the
      technique. Non-expert laboratories should use an antigen-based assay of high
      sensitivity. Only IgG class antibodies need to be measured. Useful information is
      gained by reporting the actual optical density, inhibition by high concentrations
      of heparin, and the cut-off value for a positive test rather than simply
      reporting the test as positive or negative. In making a diagnosis of HIT the
      clinician's estimate of the pretest probability of HIT together with the type of
      assay used and its quantitative result (enzyme-linked immunosorbent assay, ELISA,
      only) should be used to determine the overall probability of HIT. Clinical
      decisions should be made following consideration of the risks and benefits of
      treatment with an alternative anticoagulant. For patients with strongly suspected
      or confirmed HIT, heparin should be stopped and full-dose anticoagulation with an
      alternative, such as lepirudin or danaparoid, commenced (in the absence of a
      significant contraindication). Warfarin should not be used until the platelet
      count has recovered. When introduced in combination with warfarin, an alternative
      anticoagulant must be continued until the International Normalised Ratio (INR) is
      therapeutic for two consecutive days. Platelets should not be given for
      prophylaxis. Lepirudin, at doses adjusted to achieve an activated partial
      thromboplastin time (APTT) ratio of 1.5-2.5, reduces the risk of reaching the
      composite endpoint of limb amputation, death or new thrombosis in patients with
      HIT and HIT with thrombosis (HITT). The risk of major haemorrhage is directly
      related to the APTT ratio, lepirudin levels and serum creatinine levels. The
      patient's renal function needs to be taken into careful consideration before
      treatment with lepirudin is commenced. Severe anaphylaxis occurs rarely in
      recipients of lepirudin and is more common in previously exposed patients.
      Danaparoid in a high-dose regimen is equivalent to lepirudin in the treatment of
      HIT and HITT. Danaparoid at prophylactic doses is not recommended for the
      treatment of HIT or HITT. Patients with previous HIT who are antibody negative
      (usually so after >100 d) who require cardiac surgery should receive
      intraoperative UFH in preference to other anticoagulants that are less validated
      for this purpose. Pre- and postoperative anticoagulation should be with an
      anticoagulant other than UFH or LMWH. Patients with recent or active HIT should
      have the need for surgery reviewed and delayed until the patient is antibody
      negative if possible. They should then proceed as above. If deemed appropriate
      early surgery should be carried out with an alternative anticoagulant. We
      recommend discussion of these complex cases requiring surgery with an experienced
      centre. The diagnosis must be clearly recorded in the patient's medical record.

PMID- 16643428
TI  - Fusion of ETV6 with an intronic sequence of the BAZ2A gene in a paediatric pre-B
      acute lymphoblastic leukaemia with a cryptic chromosome 12 rearrangement.
AB  - ETV6 at 12p13 is rearranged in a variety of haematological malignancies and solid
      tumours, with more than 20 different partners having been reported. These fusions
      result in either chimeric proteins or activation of the partner gene. However,
      there are a few examples of abnormalities resulting in truncated and, most
      likely, unproductive ETV6 proteins, suggesting that haploinsufficiency of ETV6
      and/or the partner is leukaemogenic. We present a novel ETV6 rearrangement,
      identified in a paediatric pre-B acute lymphoblastic leukaemia. Fluorescence in
      situ hybridisation (FISH) and molecular genetic analyses revealed a fusion of
      ETV6 and BAZ2A (at 12q13), generated through a cryptic rearrangement between
      12p13 and 12q13, consisting of exons 1 and 2 of ETV6 and a sequence from intron 1
      of BAZ2A. This transcript is not expected to produce any chimeric protein, but
      may encode a truncated form of ETV6, containing the first 54 amino acids (aa),
      followed by 16 aa from the 3' fusion sequence, reminiscent of ETV6 fusions with
      MDS2, LOC115548, PER1, and STL. The rearrangement might also modify the
      regulation of BAZ2A by either activating a cryptic promoter or by coming under
      the control of the ETV6 promoter. The present case emphasises that 'unproductive'
      ETV6 rearrangements may play an important pathogenetic role in leukaemia.

PMID- 16643429
TI  - Promoter hypermethylation of the retinoic acid receptor beta2 gene is frequent in
      acute myeloid leukaemia and associated with the presence of CBFbeta-MYH11 fusion
      transcripts.
AB  - Silencing of the putative tumour suppressor gene retinoic acid receptor beta2
      (RARbeta2) caused by aberrant promoter hypermethylation has been identified in
      several solid tumours. In order to evaluate the extent of RARbeta2
      hypermethylation and transcription in acute myeloid leukaemia (AML) at diagnosis,
      320 patients were investigated by bisulphite-denaturing gradient gel
      electrophoresis and mRNA transcription levels were analysed in 61 of these by
      quantitative real-time polymerase chain reaction. The results were compared with
      demographic- and molecular data from the patients. While RARbeta2 was
      unmethylated in 10/10 bone marrow and 7/7 blood samples from healthy individuals,
      the gene was hypermethylated in 43% of the AML patients. The RARbeta2 degree of
      promoter methylation differed between and within individuals, and the mRNA
      transcription levels of the gene varied inter-individually by a factor of 4000. A
      significant inverse correlation between promoter hypermethylation and gene
      expression could be established (t-test, P = 0.019). Comparison of methylation
      data with a series of other molecular alterations in the same patient materials
      revealed a correlation between hypermethylation of the RARbeta2 promoter and the
      presence of CBF-MYH11 fusion transcripts (P < 0.01). Our data suggest that
      RARbeta2 promoter methylation is frequent in AML and may co-operate with the
      expression of CBF-MYH11 fusion transcripts in leukaemogenesis.

PMID- 16643430
TI  - Spectrum and significance of variants and mutations in the Fanconi anaemia group
      G gene in children with sporadic acute myeloid leukaemia.
AB  - Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi
      anaemia (FA), however, have a very high risk of developing AML. FA is a rare
      inherited disease caused by mutations in at least 12 genes, of which Fanconi
      anaemia group G gene (FANCG) is one of the commonest. To address to what extent
      FANCG variants contribute to sporadic childhood AML, we determined the spectrum
      of FANCG sequence variants in 107 children diagnosed with sporadic AML, using
      polymerase chain reaction (PCR), fluorescent single-strand conformational
      polymorphism (SSCP) and sequencing methodologies. The significance of variants
      was determined by frequency analysis and assessment of evolutionary conservation.
      Seven children (6.5%) carried variants in FANCG. Two of these carried two
      variants, including the known IVS2 + 1G>A mutation with the novel missense
      mutation S588F, and R513Q with the intronic deletion IVS12-38 (-28)_del11,
      implying that these patients might have been undiagnosed FA patients. R513Q,
      which affects a semi-conserved amino acid, was carried in two additional children
      with AML. Although not significant, the frequency of R513Q was higher in children
      with AML than unselected cord bloods. While FANCG mutation carrier status does
      not predispose to sporadic AML, the identification of unrecognised FA patients
      implies that FA presenting with primary AML in childhood is more common than
      suspected.

PMID- 16643431
TI  - Association between non-Hodgkin lymphoma and haplotypes in the TNF region.
AB  - The cytokines tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha
      (LTalpha) are known to play key roles in B-cell growth, differentiation and
      maturation. Genetic polymorphism within regulatory regions of these cytokine
      genes can alter expression levels and may be important in development of lymphoid
      malignancy. This study investigates a number of single nucleotide polymorphisms
      (SNPs) and microsatellite variants present within these genes in a large cohort
      of non-Hodgkin lymphoma (NHL) cases including 211 cases of follicular lymphoma
      (FL) and 281 cases of diffuse large B-cell lymphoma (DLBCL), and 478 unaffected
      controls. The study investigated whether particular alleles at these loci, or
      their combination across the TNF region in the form of haplotypes, may act as
      markers for predisposition and development of NHL. The study provided evidence
      for an influence of the TNF region in the susceptibility to NHL, whereby the loci
      -863, -857, TNFe and TNFd categorised five haplotype groups over which risk of
      both FL and DLBCL varied significantly. Prediction of disease risk was improved
      by the addition of loci to the haplotype, demonstrating the importance of
      considering the haplotype-specific context of the loci in genetic risk
      assessment.

PMID- 16643432
TI  - Abnormal bone remodelling and increased levels of macrophage inflammatory protein
      1 alpha (MIP-1alpha) in Waldenstrom macroglobulinaemia.
AB  - Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) and bone
      remodelling markers were evaluated in 38 patients with Waldenstrom
      macroglobulinaemia (WM) and correlated with clinical and laboratory variables.
      MIP-1alpha was elevated in WM; untreated patients had higher MIP-1alpha levels
      than patients in remission or with active disease after treatment. MIP-1alpha
      correlated with increased bone resorption, beta2-microglobulin and splenomegaly.
      Receptor activator of nuclear factor-kappaB ligand serum levels were elevated in
      WM patients; the subsequent increased bone resorption was balanced by a
      comparable elevation of osteoprotegerin production and bone formation. These
      findings may explain the absence of lytic lesions in WM patients and suggest a
      potential role of MIP-1alpha in WM.

PMID- 16643433
TI  - Overcoming graft rejection in heavily transfused and allo-immunised patients with
      bone marrow failure syndromes using fludarabine-based haematopoietic cell
      transplantation.
AB  - Allogeneic haematopoietic cell transplantation (HCT) can cure a variety of non
      malignant haematological disorders. Although transplant outcomes for selected
      patients with severe aplastic anaemia (SAA) and paroxysmal nocturnal
      haemoglobinuria (PNH) have improved, older age, allo-immunisation from
      transfusions, prior immunosuppressive therapy and a prolonged time from diagnosis
      to transplantation are associated with worse outcome. Because of its potent
      immunosuppressive effects, we investigated a fludarabine-based non-myeloablative
      conditioning regimen in patients with transfusion-dependent non-malignant
      haematological disorders at increased risk for graft rejection with conventional
      transplant conditioning. Twenty-six patients with transfusion dependent/anti
      thymocyte globulin (ATG)-refractory SAA, PNH or pure red cell aplasia underwent
      HCT from a human leucocyte antigen (HLA)-compatible relative. Transplant
      conditioning consisted of cyclophosphamide (120 mg/kg) and fludarabine (125
      mg/m2) with or without ATG. Ciclosporine, alone or combined with mycophenolate
      mofetil or methotrexate, was used as graft-versus-host disease (GVHD)
      prophylaxis. All patients achieved durable engraftment and transfusion
      independence. Twenty-four of 26 patients are alive at a median of 21 months
      following transplantation. Although a high cumulative incidence of acute (65%
      grades II-IV, 54% grades III-IV) and chronic GVHD (56%) was observed, only one
      patient died from transplant-related causes (cumulative incidence 7%). These data
      show that HCT following fludarabine-based non-myeloablative conditioning results
      in durable engraftment and excellent survival in SAA and PNH patients at high
      risk for graft rejection.

PMID- 16643434
TI  - High glucose levels enhance platelet activation: involvement of multiple
      mechanisms.
AB  - Diabetes mellitus (DM) and hyperglycaemia are associated with platelet
      activation. The present study was designed to investigate how high glucose levels
      influence platelet function. Fasting human blood was incubated with different
      concentrations of D-glucose (5, 15 and 30 mmol/l) and other sugars without or
      with in vitro stimuli. Platelet activation was monitored by whole blood flow
      cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin
      receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and
      TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30
      mmol/l L-glucose, sucrose and galactose. Hyperglycaemia also increased TRAP
      induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not
      counteract the enhancement of platelet P-selectin expression, but abolished the
      enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia.
      Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the
      hyperglycaemic enhancement of platelet P-selectin expression, but did not
      counteract the enhancement of TRAP-induced platelet fibrinogen binding.
      Hyperglycaemia did not alter platelet intracellular calcium responses to agonist
      stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3)
      kinase, or nitric oxide synthase, or the addition of insulin did not influence
      the effect of hyperglycaemia. In conclusion, high glucose levels enhanced
      platelet reactivity to agonist stimulation through elevated osmolality. This
      occurred via superoxide anion production, which enhanced platelet P-selectin
      expression (secretion), and PKC signalling, which enhanced TRAP-induced
      fibrinogen binding (aggregablity).

PMID- 16643435
TI  - The influence of anti-endothelial/antiphospholipid antibodies on fibrin formation
      and lysis on endothelial cells.
AB  - The prothrombotic mechanisms associated with antiphospholipid antibodies remain
      incompletely defined. Antibody binding to endothelial cells in vitro is a feature
      of antiphospholipid antibody-positive sera. We hypothesised that impairment of
      endothelium-dependent fibrinolysis by antiphospholipid/anti-endothelial
      antibodies is a contributory factor in the pathogenesis of thrombosis. We also
      aimed to confirm the displacement of annexin-V from endothelial cells and
      enhanced fibrin formation. Binding of immunoglobulin (Ig) from antiphospholipid
      antibody-positive sera to endothelial cells was examined using a cell-based
      enzyme-linked immunosorbent assay. Effects on fibrin formation and lysis were
      examined on cultured endothelial cell monolayers. Plasminogen activator inhibitor
      1 (PAI-1) was assayed in supernatants. We confirmed antibody binding to
      endothelial cells. With four of 14 antiphospholipid antibody-positive sera there
      was some prolongation of fibrin clot lysis time, consistent with impairment of
      endothelial fibrinolytic activity. Secretion of PAI-1 was significantly
      correlated with clot lysis time on endothelial cell monolayers incubated with
      antiphospholipid/anti-endothelial antibody-positive sera, but not with control
      sera. IgG from antiphospholipid antibody-positive sera had little effect on
      endothelial cell surface annexin-V expression. We conclude that impaired
      endothelial fibrinolysis is a potential prothrombotic mechanism in subjects with
      antiphospholipid antibodies. We were unable to confirm enhanced displacement of
      annexin-V from endothelium by antiphospholipid antibodies.

PMID- 16643436
TI  - Reversal of asymptomatic over-anticoagulation by orally administered vitamin K.
AB  - Over-anticoagulation with warfarin is common. There is good reason to reverse
      significantly high international normalised ratios (INRs), however, in practice,
      there is wide variation in the means to achieve this. Randomised controlled
      trials have provided evidence for using low dose orally administered
      phytomenadione for the reversal of asymptomatic over-anticoagulation. We devised
      an oral regimen using the intravenous preparation of phytomenadione (vitamin K1).
      Patients with an asymptomatic INR between 8.0 and 11.9 (n = 166) received 2.5 mg
      and those with an INR of 12.0-20.0 (n = 36) or >20 (n = 21) received 5 mg. Median
      INRs for the three groups of patients on day 1 (approximately 14 h) after vitamin
      K administration were 3.5, 3.0 and 2.9 respectively. In the patients given 2.5
      mg, 77% had INRs between 2.0 and 4.9 on day 1. In the patients given 5 mg, 52% of
      those presenting with INRs of 12.0-20.0 returned between 2.0 and 4.9 1 d after
      administration of vitamin K. In the INR >20 group 44% returned with an INR
      between 2.0 and 4.9. Warfarin was reintroduced once the INR was <5 and the
      majority of patients remained stable for the following 14 d. This regimen for non
      urgent correction is therefore effective and returns patients to a safe INR level
      without over-reversing anticoagulation.

PMID- 16643437
TI  - Lack of expression of the chondroitin sulphate proteoglycan neuron-glial antigen
      2 on candidate stem cell populations in paediatric acute myeloid
      leukaemia/abn(11q23) and acute lymphoblastic leukaemia/t(4;11).
AB  - It has increasingly been acknowledged that only a few leukaemic cells possess the
      capability to renew themselves and that only these self-renewing leukaemic stem
      cells are able to initiate relapses. Therefore, these leukaemic stem cells should
      be the target cells for therapy and for minimal residual disease (MRD) detection.
      Because of its presence on blasts of 11q23-rearranged high-risk leukaemic
      patients, neuron-glial antigen 2 (NG2) is thought to be a valuable marker for
      detecting leukaemic stem cells. Six acute myeloid leukaemia (AML)/abn(11q23) and
      three acute lymphoblastic leukaemia (ALL)/t(4;11) samples were analysed by four
      colour flow cytometry for NG2 expression on primitive cell populations. Candidate
      leukaemic cell populations were defined by the antigen profiles CD34+CD38- in AML
      and CD34+CD19-CD117+ in ALL. Surprisingly, in all patients these candidate stem
      cell populations were shown to lack expression of NG2. Instead, a correlation
      between the expression of the myeloid differentiation marker CD33 and increasing
      levels of NG2 on maturing cells could be demonstrated. Similarly, in ALL patients
      CD34+CD19+ cells showed a higher expression of NG2 mRNA compared with CD34+CD19-.
      Thus, NG2 appears to be upregulated with differentiation and not to be expressed
      on primitive disease-maintaining cells. This hampers the clinical use of NG2 as a
      therapeutic target and as a sensitive marker for MRD detection.

PMID- 16643438
TI  - Differential effect of leukaemogenic tyrosine kinases on cell motility is
      governed by subcellular localisation.
AB  - The chemokine, stromal cell-derived factor-1 (SDF-1) is a crucial regulator of
      stem cell homing and tethering, and potentiation of this pathway in leukaemias
      may contribute to the pathogenesis of the disease. A key second messenger in SDF
      1 signal/response coupling is phosphatidylinositol 3,4,5-triphosphate
      [PtdIns(3,4,5)P3]. SDF-1 elevated PtdIns(3,4,5)P3 levels markedly in the
      multipotent FDCP-mix stem cell line. Similarly, transfection with BCR/ABL or
      TEL/PDGFRbeta leukaemogenic tyrosine kinases chronically elevated PtdIns(3,4,5)P3
      levels. However, whilst an SDF-1 chemotactic response was observed in
      TEL/PDGFRbeta-transfected cells, in BCR/ABL cells this was markedly decreased,
      which was not due to Ras-pathway activation. Thus, multipotent cells can respond
      to SDF-1, despite chronic increases in this second messenger indicating that a
      discrete pool of SDF-1-stimulated PtdIns(3,4,5)P3 production drives the
      chemotactic response. To discern the mechanism for the differential effects of
      these oncogenes we considered subcellular localisation. As TEL/PDGFRbeta has a
      cytosolic location whilst BCR/ABL associates with actin, we removed the actin
      binding domain from BCR/ABL. We observed relocation of BCR/ABL to the cytosol and
      increased SDF-1 responses. We conclude that the localisation of BCR/ABL to the
      cytoskeleton is essential for effects on motility and moderating SDF-1 responses
      is not essential in tyrosine kinase-mediated leukaemic transformation.

PMID- 16643439
TI  - Effective treatment of a case of refractory mycosis fungoides with imatinib.

PMID- 16643440
TI  - Chronic (B cell) lymphocytic leukaemia with unusual granulation.

PMID- 16643441
TI  - A critical appraisal of the use of recombinant factor VIIa in acquired bleeding
      conditions.
AB  - Recombinant activated factor VII (rVIIa) was initially used for the treatment of
      inhibitors in patients with haemophilia. However, its localised mode of action at
      sites of damage to the vessel combined with dramatic clinical observations in
      exsanguinating patients have resulted in huge interest in its use as a global
      haemostatic agent. Although it appears safe, with no obvious excess of thrombotic
      events, its use in assorted acquired bleeding disorders, especially those
      associated with the development of complex coagulopathies, such as in the post
      trauma state, has proved to be less dramatic than hoped.

PMID- 16643442
TI  - The pathogenesis of immune thrombocytopaenic purpura.
AB  - Immune thrombocytopaenic purpura (ITP) is an autoimmune bleeding disease that is
      rarely fatal. However, in many adults treatment is unsatisfactory, with as much
      morbidity from the immunosuppressive effects of treatment as from bleeding.
      Identifying the underlying disease process should help us to identify more
      targeted therapies and improve not only the treatment but also the quality of
      life of patients with this disorder.

PMID- 16643443
TI  - William Hewson (1739-74): the father of haematology.
AB  - William Hewson has been called the father of haematology. Initially working
      alongside the Hunter brothers in London in the mid-18th century, he advanced our
      knowledge of red and white cells (but mistakenly thought some red cells started
      as white cells and could not recognise different varieties of white corpuscles),
      showed that it was fibrinogen and not the cells that led to coagulation, greatly
      advanced our knowledge of the lymphatic system in humans, fishes and amphibians,
      explored the functions of the thymus and spleen and, investigated pneumothorax
      and surgical emphysema. His life, cut short at 35 years, was often intertwined
      with those of the Hunters, Alexander Monro secundus and Benjamin Franklin. This
      paper reviews his work, his relationships and his impact on a nascent science.

PMID- 16643444
TI  - Impact of two independent bone marrow samples on minimal residual disease
      monitoring in childhood acute lymphoblastic leukaemia.
AB  - Minimal residual disease (MRD) diagnostics are used for risk group stratification
      in several acute lymphoblastic leukaemia (ALL) treatment protocols. It is,
      however, unclear whether MRD is homogeneously distributed within the bone marrow
      (BM) and whether this affects MRD diagnostics. We, therefore, analysed MRD levels
      in 141 paired BM samples (two independent punctures at different locations) from
      26 ALL patients by real-time quantitative polymerase chain reaction (PCR)
      analysis of immunoglobulin and T-cell receptor gene rearrangements. MRD levels
      were comparable in 112 paired samples (79%), whereas two samples (both taken at
      day 15) had MRD levels that differed more than threefold. In the remaining 27
      paired samples, MRD could be quantified or detected in one sample only. In four
      patients, MRD-based risk group classification was dependent on the site of BM
      puncture. Repetition of MRD analyses using 10-fold replicates instead of
      triplicates resolved most differences. In conclusion, MRD levels in paired BM
      samples were highly comparable, indicating that it is sufficient to analyse MRD
      in a single sample only. Nevertheless, MRD-based risk group classification can
      differ between paired BM samples, mainly because of variation below the
      quantitative range of the PCR assay rather than to a different distribution of
      leukaemic cells within the BM.

PMID- 16643445
TI  - Impact of age on survival after intensive therapy for multiple myeloma: a
      population-based study by the Nordic Myeloma Study Group.
AB  - The value of intensive therapy, including autologous stem cell transplantation,
      in newly diagnosed myeloma patients >60 years is not clear. We evaluated the
      impact of age (<60 years vs. 60-64 years) on survival in a prospective,
      population-based setting and compared survival with conventionally treated
      historic controls. The prospective population comprised 452 patients registered
      between 1998 and 2000. Of these, 414 received intensive therapy. The historic
      population, derived from our most recent population-based study on conventional
      therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria
      for intensive therapy. For patients undergoing intensive therapy it was found
      that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had
      independent prognostic impact on survival. However, compared with the historic
      controls a survival advantage was found both for patients <60 (median 66 months
      vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months; P =
      0.001). We conclude that in a population-based setting higher age adversely
      influences outcome after intensive therapy. Our results indicate that intensive
      therapy prolongs survival also at age 60-64 years but with less superiority than
      in younger patients.

PMID- 16643446
TI  - Ex vivo modulation of response to prednisolone in childhood acute lymphoblastic
      leukaemia.
AB  - We hypothesised that the intensity of mechanisms of glucocorticoid resistance in
      childhood acute lymphoblastic leukaemia might be decreased by concurrent ex vivo
      use of compounds with specific blocking or activating properties at different
      steps of the glucocorticoid intracellular pathway. The following modifiers were
      used: ciclosporin A, rifampicin, doxycycline, meta-iodobenzylguanidine,
      buthionine sulfoximine, ethacrinic acid, pentoxifylline, indomethacin, rotenone,
      forskolin, olomoucin, 5-aza-2'-deoxycytidine, 3-aminobenzamide, O(6)
      benzylguanidine and nitroprusside sodium. All modulators sensitised lymphoblasts
      and potentiated prednisolone cytotoxicity in most cases indicating that various
      compounds, which can influence the antileukaemic effect of prednisolone during
      anticancer therapy, might modulate some mechanisms of glucocorticoid resistance.

PMID- 16643447
TI  - Mutations of the myeloid transcription factor CEBPA are not associated with the
      blast crisis of chronic myeloid leukaemia.
AB  - The transcription factor CEBPA is crucial for normal myeloid differentiation.
      CEBPA gene mutations have been reported in patients with acute myeloid leukaemia.
      The inevitable evolution of chronic myeloid leukaemia (CML) in chronic phase (CP)
      to a fatal blast crisis (BC) is assumed to result from the acquisition of
      additional genetic changes in the leukaemic clone. Gain of CEBPA mutations might
      represent a key event causing the differentiation block observed in myeloid CML
      BC, but not in CML-CP. Here, no CEBPA mutation in 95 CML-BC patients was found,
      suggesting a limited role, if any, of CEBPA mutations in this disorder.

PMID- 16643448
TI  - The effect of red blood cells on thrombin generation.
AB  - We have developed an assay of thrombin generation in clotting whole blood.
      Because our goal was to study patients with red blood cell diseases that are
      associated with thrombosis, the initial evaluation of this assay analysed the
      effect of the haematocrit and haemolysate on the total amount of thrombin
      activity generated and the maximal concentration of thrombin achieved. Both of
      these parameters were proportional to the haematocrit throughout a wide range of
      clinically relevant cell concentrations. Red cell lysate also augmented thrombin
      generation. Because this effect was removed by filtration of the lysate, we
      propose that it was related to red cell microparticles.

PMID- 16643449
TI  - Homozygous C2362F von Willebrand factor induces intracellular retention of mutant
      von Willebrand factor resulting in autosomal recessive severe von Willebrand
      disease.
AB  - The missense mutation of cysteine 2362 to a phenylalanine in von Willebrand
      factor (VWF) has been detected in several Italian families with autosomal
      recessive, severe von Willebrand disease. We investigated how this amino acid
      change in VWF may lead to a predominantly quantitative defect. This mutation was
      studied in vitro by transient expression of the full-length mutant VWF-C2362F
      protein and in vivo by analysis of plasma VWF after infusion of 1-deamino-8-d
      arginine vasopressin (DDAVP) in a patient homozygous for this mutation. Single
      transfections of pSVHVWF-C2362F and co-transfections of mutant and wild-type
      constructs resulted in 8% and 50% VWF antigen, respectively, in conditioned
      medium. These reduced levels are in accordance with observations in homozygous
      and heterozygous carriers of the mutation. In addition, VWF-C2362F was retained
      intracellularly. Similar results were obtained for C2362F and C2362A. After
      infusion of DDAVP in a homozygous patient, a twofold decrease in half-life of
      plasma VWF-C2362F was observed. This was not explained by increased
      susceptibility of recombinant VWF-C2362F to ADAMTS13. It was concluded that VWF
      C2362F causes reduced VWF plasma levels due to impaired secretion and
      intracellular retention. Furthermore, it is the loss of cysteine 2362 rather than
      the introduction of the bulky amino acid side chain that causes these effects.

PMID- 16643450
TI  - Differential regulation of platelet aggregation and aminophospholipid exposure by
      calpain.
AB  - Aggregation, exposure of procoagulant phospholipids and shedding of
      microparticles are platelet responses that depend on activating conditions. To
      determine how these different responses are interconnected, we simultaneously
      measured fibrinogen (Fg) binding and aminophospholipid exposure on activated
      platelets by means of flow cytometry. Low calcium ionophore (A23187)
      concentrations induced Fg binding but not annexin V binding. In contrast, high
      A23187 concentrations induced annexin V binding but not Fg binding. Collagen,
      both alone and in the presence of thrombin, induced both Fg and annexin V
      binding. Dual labelling was found on 38 +/- 9% of platelets stimulated by
      thrombin plus collagen. The regulatory role of calpain in these platelet
      functions was investigated. When calpain was partially inhibited by 2 microg/ml
      calpeptin, Fg binding still occurred but aminophospholipid exposure was limited.
      By contrast, complete inhibition of calpain by 100 microg/ml calpeptin or E64d
      decreased Fg binding but enhanced aminophospholipid exposure. In these latter
      conditions, cytosolic calcium-extruding systems were inhibited. The results
      suggest that (i) conditions that favour aminophospholipid exposure tend to
      decrease the aggregation process and (ii) calpain determines the switch to either
      aggregation or aminophospholipid exposure by controlling intracellular calcium.

PMID- 16643451
TI  - Sulphydryl modifications alter scramblase activity in murine sickle cell disease.
AB  - Increased oxidant stress has been suggested to play a role in the process of
      phosphatidylserine (PS) externalization in the red blood cells of sickle cell
      patients. Inhibition of the ATP-driven translocation from outer to inner
      monolayer (flippase) by sulphydryl modification has been established. The present
      study showed that phospholipid scrambling was also sensitive to protein
      sulphydryl modification. Treatment with N-ethylmaleimide lead to enhanced PS
      exposure and a lower Ca(++) requirement for scrambling. In contrast,
      pyridyldithioethylamine treatment inhibited PS exposure. Red blood cells from a
      murine model for sickle cell disease exhibited a reduced response to both
      reagents, suggestive of previous sulphydryl modifications to the protein(s)
      involved in phospholipid scrambling. We conclude that sulphydryl modifications to
      both scramblase and flippase underlie the enhanced formation of PS-exposing cells
      in sickle cell disease.

PMID- 16643452
TI  - Pulmonary hypertension in thalassaemia major patients with normal left
      ventricular systolic function.
AB  - Pulmonary hypertension is common in adults with thalassaemia and other haemolytic
      anaemias. It was hypothesised that regular transfusions in thalassaemia major
      should both decrease the chronic haemolytic rate and be protective from pulmonary
      hypertension (PHT). To reduce the contribution of existing cardiac disease to
      PHT, the subjects were limited to patients with normal left ventricular
      shortening fractions. Associations with multiple laboratory markers of
      haemolysis, serum ferritin levels, chest X-rays findings and splenectomy status
      were also considered. We found no biochemical, transfusional, or clinical (except
      gender) differences in transfused thalassaemia patients with or without pulmonary
      hyper tension.

PMID- 16643453
TI  - Identification of an erythroid ATP-dependent aminophospholipid transporter.
AB  - The asymmetric distribution of amino-containing phospholipids in plasma membranes
      is essential for the function and survival of mammalian cells. Phosphatidylserine
      (PS) is restricted to the inner leaflet of plasma membranes by an ATP-dependent
      transport process. Exposure of PS on the surface of cells serves as a binding
      site for haemostatic factors, triggers cell-cell interaction and recognition by
      macrophages and phospholipases. Exposure of PS on the red cell surface plays a
      significant role in sickle cell pathology. We report the identification of two
      different isoforms of the aminophospholipid translocase, Atp8a1, or flippase, in
      the murine red blood cell membrane.

PMID- 16643454
TI  - Infantile pyknocytosis: a cause of haemolytic anaemia of the newborn.
AB  - This study defined the incidence, clinical and haematological characteristics of
      infantile pyknocytosis in a monocentric retrospective study of 149 blood samples
      referred for unexplained neonatal haemolytic anaemia. Pyknocytosis was diagnosed
      in 14 patients (9.4%). All patients had neonatal jaundice and severe anaemia
      (mean nadir haemoglobin: 6.8 g/dl) at a mean age of 21 d. The percentage of
      pyknocytes was 4-23%. Packed red blood cell transfusions were needed in 11 of 14
      patients. Haemoglobin levels reached normal values within a mean time of 4
      months. Infantile pyknocytosis is an unusual cause of neonatal haemolytic
      anaemia, which requires careful examination of blood smears.

PMID- 16643455
TI  - Inhibition of erythroid progenitor cell growth by anti-Ge3.

PMID- 16643456
TI  - Evidence of genetic heterogeneity in congenital dyserythropoietic anaemia type I.

PMID- 16643458
TI  - The association between FANCD1/BRCA2 mutations and leukaemia.

PMID- 16643459
TI  - Acute lymphoblastic leukaemia in Noonan syndrome.

PMID- 16643465
TI  - Current trends in the management of Wilms' tumour.

PMID- 16643466
TI  - Haematuria in prostate cancer: new solutions for an old problem.

PMID- 16643467
TI  - Laparoscopic urological surgery: mentor matters.

PMID- 16643468
TI  - Dietary advice for patients with renal stones: are we practising evidence-based
      medicine?

PMID- 16643469
TI  - Clinical trials in patients with biochemically relapsed prostate cancer.
AB  - In this section there is a wide diversity of mini-reviews, covering several areas
      of interest for readers. Authors from the USA write about clinical trials in
      patients with biochemically relapsed prostate cancer, again bridging the divide
      between medical oncologists and urologists who specialise in urological
      oncological surgery. The second paper is a joint one from Germany and the USA,
      bringing the reader up to date with advances in the treatment of stress urinary
      incontinence. Finally there are two papers from Australia describing the use of
      positron emission tomography in renal cancer and in prostate cancer.

PMID- 16643470
TI  - Advancing the treatment of stress urinary incontinence.

PMID- 16643471
TI  - Positron emission tomography (PET), immuno-PET and radioimmunotherapy in renal
      cell carcinoma: a developing diagnostic and therapeutic relationship.

PMID- 16643472
TI  - Positron emission tomography and molecular imaging of the prostate: an update.

PMID- 16643473
TI  - Renal cell carcinoma local recurrences: impact of surgical treatment and
      concomitant metastasis on survival.
AB  - OBJECTIVE: To analyse the survival benefit of resecting local recurrence (LR) of
      renal cell carcinoma (RCC) in the presence and absence of concomitant metastasis.
      PATIENTS AND METHODS: From 1989 to 2004 we identified 34 patients with LRs (2.9%)
      of the 1165 radical nephrectomies performed for T1-4N0M0 disease. Of these, 18
      (53%) had no evidence of metastasis (isolated LR incidence, 1.5%) and 16 (47%)
      had synchronous metastasis. Of the 18 patients with no metastasis, 11 had
      complete surgical resection (group I) and seven had nonsurgical therapy (group
      II). Of the 16 patients with synchronous metastasis, five had surgery (group III)
      and 11 did not (group IV). Survival was projected using the Kaplan-Meier method
      and log-rank test for each group. RESULTS: Eight of the 34 patients (24%) were
      symptomatic. The T stage of the initial nephrectomy was T1a in two cases, T1b in
      six, T2 in five, T3a in six, T3b in eight, T4 in six and unknown in one; 22
      patients (65%) had clear cell histology. There were no significant differences in
      median time to LR or the LR size among the groups. The median (range) follow-up
      was 16.9 (0.5-103.6) months. Of the 11 patients in group I, three remain with no
      evidence of disease, three are alive with metastatic disease, and five died from
      disease. By contrast, 21 of the 23 patients (91%) in groups II, III and IV died
      from disease. The overall estimated 1-, 3- and 5-year survivals were 63%, 31% and
      18%. The median survival time was 71.4 months for group I, 9.9 for II, 16.3 for
      III, and 11.8 for IV (P < 0.01) with a 5-year survival of 62% for group I and 0%
      for groups II, III, and IV. CONCLUSIONS: LR after radical nephrectomy is rare
      (2.9%) and has a poor prognosis. The presence of synchronous metastasis and
      nonoperative therapy are related to these low survival rates. However, if there
      is no metastatic disease, complete surgical resection of LRs is associated with
      improved survival.

PMID- 16643474
TI  - Comparison of outcomes in elective partial vs radical nephrectomy for clear cell
      renal cell carcinoma of 4-7 cm.
AB  - OBJECTIVE: To compare the outcomes of patients who had a elective partial
      nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma
      (RCC) of 4-7 cm. PATIENTS AND METHODS: From March 1998 to July 2004, 45 and 151
      patients underwent PN and RN, respectively, for clear cell RCC. A multivariate
      Cox model was constructed for disease-free survival with adjustment for markers
      of disease severity, and a propensity-score approach used as a confirmatory
      analysis. RESULTS: In the PN and RN cohorts the treatment failed in one and 20
      patients, respectively; the median follow-up was 21 months. The hazard ratio (95%
      confidence interval) for PN after adjusting for disease severity was 0.36 (0.05
      2.82; P = 0.3). Using planned PN as a predictor (intent-to-treat analysis) the
      hazard ratio was 1.06 (0.32-3.53; P = 0.9). In the propensity-score model,
      planned PN was associated with a hazard ratio of 1.75 (0.50-6.14; P = 0.4). The
      serum creatinine level 3 months after surgery was significantly lower in patients
      who had PN, with a difference between the means of 0.36 (0.23-0.48; P < 0.001).
      CONCLUSIONS: Renal function was preserved after PN for 4-7 cm clear cell RCC
      tumours. When comparing the outcomes of PN and RN it is important to consider the
      intended operation as an independent variable. There was no clear evidence that
      PN was associated with worse cancer control, although a continued follow-up of
      this and other cohorts is warranted.

PMID- 16643475
TI  - Incidental renal tumours: the frequency of benign lesions and the role of
      preoperative core biopsy.
AB  - OBJECTIVE: To determine the incidence of benign renal lesions in incidentally
      discovered small renal tumours, increasingly detected by the widespread use of
      abdominal imaging, and to evaluate whether preoperative renal core biopsy is
      effective in identifying benign lesions. MATERIALS AND METHODS: In a
      retrospective study, renal core biopsies for incidental tumours over a 5-year
      period were analysed. The biopsies were correlated with the final pathology of
      the nephrectomy specimens, or with patient follow-up if nephrectomy was avoided.
      RESULTS: Of 70 diagnostic core biopsies, a third of cases were considered benign.
      The sensitivity and specificity for both benign and malignant lesions when
      compared to definitive pathology was 100% in all cases subjected to nephrectomy.
      Of the 30 non-diagnostic biopsies, three were proved to be benign, and 18 likely
      to be benign. The only complication of renal biopsy was one case of bleeding
      after biopsy. CONCLUSION: A higher than previously anticipated proportion of
      incidentally detected small renal masses are benign. Given the high sensitivity
      and specificity, there is value in taking a core biopsy of small incidental renal
      lesions, a procedure with a low complication rate (1%). When analysed by a
      pathologist familiar with renal biopsy, this might avoid radical nephrectomy in
      many patients.

PMID- 16643476
TI  - Immunostaining for placental alkaline phosphatase on fine-needle aspiration
      specimens to detect noninvasive testicular cancer: a prospective evaluation in
      cryptorchid men.
AB  - OBJECTIVE: To assess, in a 12-year prospective study, the potential for early
      detection of testicular carcinoma in situ (CIS) by immunocytochemistry, using
      anti-placental alkaline phosphatase (PLAP) monoclonal antibodies on testicular
      fine-needle aspiration cytology (FNAC) specimens taken from a group of formerly
      cryptorchid patients, as such men are at greater risk of developing testicular
      cancer. PATIENTS AND METHODS: Sixty-eight men who had had orchidopexy at the
      Urological Department of the University of Padova between 1975 and 1983 were
      evaluated first in 1993, by a protocol including a history, physical examination,
      testicular ultrasonography and serum tumour markers, to eliminate the presence of
      testicular cancer. In 57 of the 68 men, specimens taken from bilateral testicular
      FNAC were stained immunocytochemically using anti-PLAP monoclonal antibodies.
      After 8 years, the same protocol was repeated on the 57 men, and the follow-up
      was prolonged until March 2005 for men with previous positive PLAP
      immunostaining. RESULTS: In 1993, six of the 57 men, (10.5%) had unilateral
      positive immunostaining for PLAP. By 2001, none of these men had developed
      testicular cancer, while of the other 51 men, only one developed a
      nonseminomatous tumour. The uninterrupted surveillance of PLAP-positive men
      showed no overt cancer until March 2005. CONCLUSION: The present findings do not
      seem to confirm the reliability of PLAP immunostaining of testicular specimens
      from FNAC for detecting CIS. These findings might depend on the geographical
      variability of both CIS and testicular cancer incidence, as well as on the
      variable relationship between CIS and successive occurrence of invasive testis
      cancer.

PMID- 16643477
TI  - Health-related quality of life and satisfaction with care among older men treated
      for prostate cancer with either radical prostatectomy or external beam radiation
      therapy.
AB  - OBJECTIVE: To analyse health-related quality of life (HRQoL) and satisfaction
      with care across potential curative treatments for older patients newly diagnosed
      with prostate cancer. PATIENTS AND METHODS: In a prospective cohort study we
      recruited 115 older patients (> or =65 years) newly diagnosed with prostate
      cancer from the urology clinics of an urban academic and a Veterans'
      Administration (VA) hospital. Patients completed generic (Short Form-36),
      prostate-specific (University of California Los Angeles Prostate Cancer Index)
      HRQoL, and Client Satisfaction with Care (CSQ-8) surveys before treatment with
      either radical prostatectomy (RP) or external beam irradiation (EBRT) and at 3, 6
      and 12 months afterward. Clinical and demographic data were obtained via medical
      chart review. A repeated-measures analysis of variance was used to examine
      changes in generic and prostate cancer-specific HRQoL between treatments. Log
      linear regression was used to analyse the factors associated with 12-month HRQoL
      scores, and Kaplan-Meier survival curves were used to compare the return to
      baseline values for HRQoL. RESULTS: The RP group had significantly higher income,
      education and better general health than the EBRT group. Age (odds ratio 0.5, 95%
      confidence interval 0.32-0.82), non-VA hospital (28.8, 2-402) and prostate
      specific antigen level at diagnosis (2.8, 1.05-7.5) were associated with RP. The
      analysis results indicated that the RP group had higher scores for generic HRQoL
      subscales of physical function (P = 0.019), role emotional (P = 0.037), vitality
      (P = 0.033) and general health (P = 0.05) than the EBRT group. A log-linear
      regression model for predicting the 12-month scores showed that RP was associated
      with higher scores for most of the generic HRQoL and bowel function (odds ratio
      1.12, P = 0.03), urinary bother (1.6, P = 0.014) and bowel bother (1.5, P =
      0.013). Being older was associated with a lower score on bowel function (0.98, P
      = 0.05) and sexual function (0.92, P = 0.05). Satisfaction with care was
      comparable between treatment groups at baseline and at the follow-up.
      CONCLUSIONS: Older patients tolerate RP well from the HRQoL perspective and thus
      decisions for therapy in this age cohort should not be based primarily on age.

PMID- 16643478
TI  - Third-generation cryotherapy for prostate cancer in the UK: a prospective study
      of the early outcomes in primary and recurrent disease.
AB  - OBJECTIVE: To present the early results of the use of third-generation
      cryotherapy in primary and recurrent prostate cancer at one UK centre. PATIENTS
      AND METHODS: Over a 14-month period 51 patients underwent cryotherapy for
      prostate cancer. In 31 patients cryotherapy was used as the primary treatment and
      in 20 as a salvage treatment after radiotherapy or hormone ablation. Data were
      collected prospectively and the median follow-up was 9 months. RESULTS: The
      prostate-specific antigen (PSA) level decreased to <0.5 ng/mL in 79% of patients
      undergoing primary treatment and in 67% of patients undergoing salvage treatment.
      A higher Gleason grade and PSA levels were associated with a poorer outcome. No
      patient developed a fistula, 4% developed urinary retention requiring
      transurethral prostatectomy and 4% had persistent incontinence. The rates of
      erectile dysfunction were high (86%). The median inpatient stay was 2 days.
      CONCLUSION: Early results suggest that cryotherapy offers a safe alternative for
      primary and recurrent prostate cancer, particularly for older and less fit
      patients. Long-term data are required to assess the durability of response and
      the effect on survival.

PMID- 16643479
TI  - Laparoscopic radical prostatectomy: minimum 3-year follow-up of the first 100
      patients in the UK.
AB  - OBJECTIVE: To present the results of the first 100 patients in the UK treated by
      laparoscopic radical prostatectomy (LRP) and with at least 3 years of follow-up,
      as LRP continues to develop as a minimally invasive alternative to open radical
      prostatectomy. PATIENTS AND METHODS: In all, 100 patients (mean age 62 years,
      range 52-72) had a transperitoneal LRP by one surgeon during a 25-month period
      from 2000 to 2002. Most (78%) patients had a prostate-specific antigen level of 4
      10 ng/mL, clinical stage T1 disease (62%), and Gleason 6 on biopsy (50%). Sixty
      four patients had unilateral or bilateral nerve preservation and 14 had pelvic
      lymphadenectomy. RESULTS: The mean operative duration was 245 min, with a 1%
      conversion rate. Three patients received a blood transfusion and three had major
      complications, including a rectal injury. The positive margin rate was 16% and
      correlated with pathological variables. At > or = 3 years of follow-up (mean 3.7)
      the overall survival rate was 99% and the biochemical progression-free survival
      was 88% in all patients, at 90% for pT2 and 75% for pT3. Ninety patients used 0-1
      pads/day (84% pad-free) and 60 undergoing nerve preservation retained erectile
      function. CONCLUSION: This series includes the first results for LRP with a > or
      = 3-year follow-up reported from the UK, with oncological control and morbidity
      comparable to those in previously published open and laparoscopic series. The
      history of open radical prostatectomy suggests that as the technique of LRP
      develops and experience with it increases, these results are likely to improve.

PMID- 16643480
TI  - Disease progression and survival in patients with prostate carcinoma and positive
      lymph nodes after radical retropubic prostatectomy.
AB  - OBJECTIVE: To determine disease progression and survival in patients with lymph
      node-positive prostate carcinoma after ascending radical retropubic prostatectomy
      (RP) and pelvic lymphadenectomy with different forms of postoperative adjuvant
      treatment. PATIENTS AND METHODS: We analysed 82 patients with lymph node
      metastases at the time of surgery and who had a RP between 1993 and 2002. Data
      from clinical records and follow-up questionnaires were used. Overall survival,
      time to clinical disease progression and time to biochemical progression were
      used as endpoints to assess the outcome. Clinical progression was defined as
      documented local recurrence or distant metastases, and biochemical as an increase
      in prostate-specific antigen (PSA) of > or = 0.4 ng/mL. Variables analysed
      included PSA level, Gleason score before and after RP, clinical and pathological
      stage, number of positive lymph nodes and hormone therapy after RP. The
      statistical assessment included univariate regression analysis, and to analyse
      the distribution of clinical findings in different groups, Mantel-Haenszel
      statistics were used to test for differences in the numbers of patients. Survival
      and progression-free interval were assessed by Kaplan-Meier estimates and
      differences between groups calculated by log-rank statistics and Cox regression
      models. RESULTS: The median (range) follow-up was 55 (10-125) months. Adjuvant
      hormonal treatment was used in 77 patients, five of whom had immediate adjuvant
      radiotherapy, and nine delayed radiotherapy because of local progression or
      symptomatic bone metastases; five had no additional treatment. The rates for 5-
      and 10-year overall survival, clinical progression-free survival and biochemical
      progression-free survival were 84% and 79%, 83% and 77%, and 70% and 60%,
      respectively. Ten patients died (12%), eight (10%) of them from the cancer; bone
      metastases were detected in nine (11%). Local recurrences developed in three (4%)
      patients, 10 (12%) had a PSA increase of > or = 0.4 ng/mL alone and 58 (71%) had
      no signs of progression, but two died from other causes. CONCLUSIONS: Most
      patients with prostate cancer who had RP and pelvic lymphadenectomy followed by
      adjuvant hormone therapy, and who had lymph node metastases at the time of
      surgery, had excellent overall and progression-free survival in the long term.

PMID- 16643481
TI  - Integral spectrophotometric analysis of 5-aminolaevulinic acid-induced
      fluorescence cytology of the urinary bladder.
AB  - OBJECTIVE: To evaluate whether tumour cells can be detected in bladder lavage
      fluid samples by an objective spectrofluorometric method, as 5-aminolaevulinic
      acid (ALA)-induced fluorescence endoscopy (AFE) and cytology are promising
      valuable tools for detecting transitional cell carcinoma of the urinary bladder
      (TCCB). MATERIALS AND METHODS: After instilling ALA into the urinary bladder,
      lavage samples were collected and their sediments analysed spectroscopically
      under blue excitation at approximately 400 nm wavelength. During AFE, biopsies
      were taken. From 62 cases, 24 patients had a histologically confirmed TCCB (group
      A), 28 had a history of TCCB but no evidence of disease (group B) and 10 were
      negative for TCCB (group C). RESULTS: Lavage sediments of all patients fluoresced
      in the green spectral range, typical of cellular autofluorescence. Sediments of
      all patients of group A caused red fluorescence peaking at 635 nm, indicating
      protoporphyrin IX (PPIX). The PPIX signals derived from bleaching spectra were
      significantly different between benign and malignant findings (P = 0.001). There
      was another red fluorescence peak at approximately 620 nm; in 19 cases its
      intensity exceeded the intensity of the PPIX signal. CONCLUSIONS:
      Spectrofluorometric analysis of lavage sample sediments can be used to detect
      tumour-associated red fluorescence of PPIX in TCCB. Immediate significant and
      objective measurements are possible, which could be further automated for the
      rapid diagnosis of TCCB.

PMID- 16643482
TI  - Efficacy and tolerability of tolterodine extended-release in men with overactive
      bladder and urgency urinary incontinence.
AB  - A group of authors from the USA evaluated the efficacy and tolerability of
      tolterodine extended-release on objective and subjective endpoints in men with an
      overactive bladder. They found that it significantly reduced incontinent episodes
      and improved patient perception of treatment benefit in men with an overactive
      bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine
      extended-release (ER) on objective and subjective endpoints in men with
      overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND
      METHODS This was a post hoc analysis of data collected from men with OAB enrolled
      in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once
      daily; tolterodine ER registration trial) and included men with urinary frequency
      (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes
      were assessed using 7-day bladder diaries. Patient perception of treatment
      benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded
      throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine
      ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical
      characteristics were similar for the two treatment groups. Compared with placebo,
      tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs
      - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving
      tolterodine ER had fewer micturitions/24 h, but this was not a significant
      difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly
      more men treated with tolterodine-ER (63%) than placebo-treated men (46%)
      reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly
      reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs
      7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and
      somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms
      suggestive of urinary retention that led to his withdrawal from the study. None
      of the men had acute urinary retention requiring catheterization. CONCLUSION: In
      men with OAB and urgency UI, tolterodine ER was well tolerated and significantly
      reduced episodes of urgency UI, and improved patient perception of treatment
      benefit.

PMID- 16643483
TI  - alpha-blocker monotherapy in the treatment of nocturia in men with lower urinary
      tract symptoms: a prospective study of response prediction.
AB  - OBJECTIVE: To determine the efficacy of an alpha-adrenoceptor antagonist,
      terazosin, in reducing nocturia in men with lower urinary tract symptoms (LUTS),
      and to identify the factors predicting treatment outcome. PATIENTS AND METHODS:
      In all, 100 patients were treated with 2 mg of terazosin once daily for the first
      7 days, and continued to receive 4 mg of terazosin once daily for the following 3
      weeks. The men were assessed at baseline and at the end of treatment using
      uroflowmetry, the International Prostate Symptom Score (IPSS), and the degree of
      nocturia estimated from a frequency-volume chart (FVC) and objectively. RESULTS:
      On the FVC, 27 patients reported that the terazosin treatment reduced their
      nocturia by more than half, and 14 reported a reduction of 25-49%. On the IPSS,
      31 patients reported that the treatment reduced their nocturia by more than half
      and 27 reported a reduction of 25-49%. On multivariate regression analysis, only
      the actual number of nightly voids on the FVC was associated with a 2.1-fold
      chance of an improvement of >25% in objective nocturia (P = 0.016). Using a
      comparable model, a greater nocturia score on the IPSS was associated with a
      higher likelihood of improvement in subjective nocturia (odds ratio, 1.653; 95%
      confidence interval, 1.079-2.533; P = 0.021). CONCLUSION: Treatment with
      terazosin can reduce patients' episodes of nocturia both subjectively and
      objectively in some men with LUTS. Our results suggest that both subjective and
      objective numbers of nocturia episodes are associated with improvements in
      subjective and objective nocturnal frequencies, respectively.

PMID- 16643484
TI  - The effects of isolated posterior compartment defects on lower urinary tract
      symptoms and urodynamic findings.
AB  - OBJECTIVES: To determine any significant patterns among subjective and/or
      objective storage or voiding variables in women with isolated rectoceles or
      posterior enteroceles. PATIENTS AND METHODS: We retrospectively reviewed the
      charts of 23 women with isolated posterior compartment defects. Patient
      histories, physical examination findings, catheterized postvoid residual urine
      volume (PVR) after uroflowmetry, and urodynamic evaluations were reviewed. Lower
      urinary tract symptoms (LUTS) were classed as pure storage (urgency, frequency,
      nocturia, etc.), pure voiding (hesitancy, straining, positional voiding, etc.),
      or mixed. RESULTS: The mean (range) age of the women was 67 (48-85) years. On
      physical examination, 15 women had a grade 3 defect, and eight a grade 2 defect.
      Thirteen women reported symptoms related to their prolapse (vaginal bulge,
      splinting with defecation): nine reported pure storage symptoms, one pure voiding
      symptoms, and 12 mixed symptoms; two women relied on catheterization for bladder
      emptying. Only one woman reported no LUTS. An elevated PVR (>100 mL) was found in
      11 women (48%). Urodynamic studies were available for 17 women, and revealed
      detrusor overactivity in nine of them. There were low maximum urinary flow rates
      (Qmax < or = 15 mL/s) in 12 of the 17 women, and high voiding pressures at Qmax
      (P(det.Qmax) > or = 20 cmH2O) in 10. Both findings were present in seven of the
      17 women. There was evidence of abdominal straining to void in nine of the 17
      women. CONCLUSIONS: The overwhelming majority of women with isolated posterior
      compartment defects reported bothersome LUTS and most had abnormal urodynamic
      variables. The findings suggest that significant posterior prolapse defects can
      cause bladder outlet obstruction.

PMID- 16643485
TI  - Flow meter urine testing: a practical proposition in patients attending for
      urodynamics?
AB  - OBJECTIVE: To find a practical way of detecting urinary tract infection (UTI)
      before invasive urodynamic testing, as UTIs after urodynamics are well
      documented, but there are no standard guidelines about when urine should be
      analysed before urodynamics. PATIENTS AND METHODS: Before urodynamics all
      patients are asked to provide a free urine flow; the patient is then catheterized
      to obtain a catheter-specimen of urine that is tested for infection by a urine
      dipstick. If the dipstick is found positive for nitrites and/or leukocytes, the
      test is abandoned and the sample sent for microscopy, culture and sensitivity. In
      the present study, patients were asked to provide a free urine flow into the
      flowmeter as usual. Between patients, the flowmeter was washed with soap and
      water and dried, so that there would be no cross-contamination between patients'
      urine results. Urine was collected as usual and tested using a dipstick, the
      patient was then catheterized and another dipstick test done on the catheter
      specimen of urine (CSU), to compare results. RESULTS: Pairs of urine samples,
      when positive for nitrite were 100% consistent, and 89% of pairs positive for
      leukocytes were the same before and after catheterization. The remaining 11% (all
      women) of the positive leukocyte group had leukocytosis on testing the flowmeter
      urine but not on the CSU, possibly due to contamination from the vagina.
      CONCLUSION: Testing urine by dipstick in the sample from the flowmeter is a
      feasible option, thus saving the patient an inappropriate catheterization, with
      the risk of bacteraemia during urodynamics, and allowing the flowrate to be
      measured.

PMID- 16643486
TI  - What is the optimum dose of type A botulinum toxin for treating neurogenic
      bladder overactivity?
AB  - OBJECTIVE: To assess the effects of two doses of botulinum toxin A (Dysport,
      Ipsen-Biotech, France; 500 and 1000 Speywood units, SU) injected into the bladder
      for treating incontinence due to a neurogenic overactive bladder. PATIENTS AND
      METHODS: In an open-label, prospective study between October 2002 and May 2004,
      in two centres, we analysed the effects of successive doses of 500 and 1000 SU of
      Dysport, endoscopically injected into the detrusor muscle. At each step, patients
      (26 women and 19 men) were re-evaluated at 1 month (clinical evaluation and
      pressure-flow study). If there was a 'good' clinical response (complete absence
      of urinary leakage) the patient was observed until incontinence recurred;
      otherwise a further injection was administered at a higher dose. RESULTS: The
      mean (sd, range) follow-up was 22 (0.75, 5-31) months; 11 of the 45 patients
      (24%) did not respond primarily at 1 month for both doses. The analysis of the
      two curves of survival with no re-injection of Dysport showed a statistically
      longer action at 1000 SU (P = 0.016). However, in this group there was one
      patient with general muscle weakness and asthenia, which could have been related
      to the injection. CONCLUSIONS: The optimum dose of Dysport for incontinence
      secondary to a neurogenic overactive bladder is not yet defined; 1000 SU probably
      has a more prolonged effect than 500 SU but exposes the patient to major
      complications. Further studies evaluating the clinical effect of 750 SU of
      Dysport are necessary.

PMID- 16643487
TI  - Effects of magnetic stimulation in the treatment of pelvic floor dysfunction.
AB  - OBJECTIVE: To correlate, in a pilot study, the clinical results of extracorporeal
      magnetic innervation therapy (ExMI) of the pelvic floor muscles with functional
      changes in the pelvic floor musculature, urodynamics and quality of life.
      PATIENTS AND METHODS: In all, 74 patients (65 women and nine men) with urge
      incontinence, urgency/frequency, stress incontinence, mixed incontinence and
      defecation problems were included in a prospective study of ExMI using a
      'electromagnetic chair'. All patients were treated twice weekly for 8 weeks.
      Digital palpation and biofeedback with a vaginal or anal probe were used for
      registration of the pelvic floor musculature. A urodynamic evaluation, a voiding
      diary, a pad-test, the King's Health Questionnaire (KHQ) and a visual analogue
      scale (VAS) were completed by the patient at baseline and at the end of the
      study. RESULTS: In the group as a whole, there were no significant differences in
      the voiding diary, pad-test, quality of life, VAS score, biofeedback registration
      and urodynamics before and after treatment. Additional stratification was applied
      to the total patient group, related to the pretreatment rest tone of the pelvic
      floor, the basal amplitude registered on electromyography, to age and to previous
      treatments. However, there were no significant differences in the data before and
      after treatment within all subgroups (stress incontinence, urge incontinence,
      urgency/frequency, defecation problems, overactive pelvic floor, age, previous
      treatments), except for the KHQ domain of 'role limitations', where there was a
      significant improvement in all groups. CONCLUSION: ExMI did not change pelvic
      floor function in the present patients. The varying outcomes of several studies
      on ExMI stress the need for critical studies on the effect and the mode of action
      of electrostimulation and magnetic stimulation. In our opinion 'the chair' is
      suitable to train awareness of the location of the pelvic floor. However, active
      pelvic floor muscle exercises remain essential.

PMID- 16643488
TI  - Incidental acute prostatic inflammation is associated with a lower percentage of
      free prostate-specific antigen than other benign conditions of the prostate: a
      prospective screening study.
AB  - OBJECTIVE: To evaluate the performance of percentage free/total prostate-specific
      antigen (f/tPSA) as a screening tool for prostate cancer, and to assess the
      impact of prostatic inflammation on f/tPSA. PATIENTS AND METHODS: Men aged 50-65
      years were invited for prostate cancer screening. Biopsies were taken from men
      with a tPSA of > or = 4 ng/mL, together with those with a tPSA of 1.1-3.99 ng/mL
      and a f/tPSA of < or = 20%. Histological evidence of prostate cancer, acute
      inflammation, chronic inflammation, and benign prostatic tissue were noted in
      biopsy cores, together with the associated f/tPSA values. RESULTS: The cancer
      detection rate was 4.3% (33/773). Evidence of inflammation was found in about
      half (87/175) of those biopsied. Men with acute inflammation (27/175, 15%) had
      significantly lower serum f/tPSA values (mean 13.4%) than those with chronic
      inflammation (mean 16.6%, P = 0.002) and benign prostatic tissue (mean 15.7%, P =
      0.034), but were similar to men with prostate cancer (mean 15.3%, P = 0.315).
      CONCLUSIONS: In this prospectively screened cohort of men, there was a high
      incidence of asymptomatic inflammation on prostatic histology; f/tPSA values were
      significantly lower in men with acute inflammation. This might explain the
      variability of f/tPSA in improving specificity when used as a screening tool for
      prostate cancer, and might also reduce its effectiveness in differentiating
      tumours with more aggressive potential.

PMID- 16643489
TI  - Interleukin-8 levels in seminal plasma in chronic prostatitis/chronic pelvic pain
      syndrome and nonspecific urethritis.
AB  - OBJECTIVE: To investigate whether a range of cytokines were detectable in the
      seminal plasma and urine of men with chronic prostatitis/chronic pelvic pain
      syndrome (CP/CPPS) and nonspecific urethritis (NSU), and whether cytokine levels
      correlated with symptom severity in CP/CPPS. PATIENTS AND METHODS: In all, 87 men
      participated, 33 with CP/CPPS, 31 with NSU, and 23 controls. Interleukin (IL)
      1beta, IL-2, IL-6, IL-8 and IL-10 were measured in seminal plasma and first pass
      urine, and the results were correlated with scores for pain, urinary symptoms and
      quality-of-life impact using a validated symptom index, the National Institutes
      of Health Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: Seminal plasma
      levels of IL-8 were higher in men with CP/CPPS and NSU than in controls (P <
      0.001), and the levels correlated with NIH-CPSI symptom scores in men with
      CP/CPPS. There were no significant differences in urinary IL-8 levels in the
      three groups, and no significant differences in levels of the other cytokines in
      either semen or urine. CONCLUSION: Semen IL-8 levels correlate with subjective
      symptoms in men with CP/CPPS. IL-8 might contribute to the pathophysiology of
      CP/CPPS and NSU, and elevated levels might be a useful marker of the condition.

PMID- 16643490
TI  - Fluid shear stress-induced nitric oxide production in human cavernosal
      endothelial cells: inhibition by hyperglycaemia.
AB  - OBJECTIVE: To investigate whether fluid shear stress (FSS) induces endothelial
      nitric oxide synthase (eNOS) activity and NO production in isolated human corpus
      cavernosal endothelial cells (HCCECs), and whether this response is altered
      during hyperglycaemia in vitro, as haemodynamic signalling during penile erection
      induces eNOS-mediated NO production in vivo. MATERIALS AND METHODS: ECs were
      cultured from HCC and characterized by the uptake of acetylated low-density
      lipoprotein and the expression of von Willebrand factor, VE-cadherin, CD31 and
      eNOS. HCCECs were exposed to FSS (1.2 Pa (12 dynes/cm2), 5 min) using a cone-and
      plate viscometer in the presence or absence of high glucose (30 mm, 48 h). The
      phosphorylation of ser1177 on eNOS and total eNOS protein expression after FSS
      was examined by Western blot. NO in the conditioned media was assessed by
      measuring nitrate and nitrite levels. RESULTS: Compared to static conditions, FSS
      induced a significant increase in the phosphorylation of eNOS on ser1177 in
      HCCECs, and the release of NO to the conditioned media. Treatment of HCCECs with
      high glucose levels did not alter the ratio FSS-induced phosphorylated eNOS/total
      eNOS, but did result in the down-regulation of total eNOS and significantly
      attenuated FSS-induced NO release. CONCLUSION: These in vitro data suggest that
      FSS contributes to eNOS activation and NO release in HCCECs, and supports in vivo
      reports suggesting a role for haemodynamic signalling in the erectile response.
      Treatment with high glucose levels prevented FSS-induced NO release, suggesting a
      mechanism that may contribute to decreased erectile function associated with
      diabetes.

PMID- 16643491
TI  - Metabolic abnormalities associated with calyceal diverticular stones.
AB  - OBJECTIVE: To review the metabolic analyses of patients with calyceal
      diverticular stones who had surgical treatment of their calculi and to examine
      the effect of selective medical therapy on stone recurrence, as recent reports
      suggest that metabolic abnormalities contribute to stone development. PATIENTS
      AND METHODS: In all, 37 patients who had endoscopic treatment of symptomatic
      calyceal diverticular calculi were retrospectively reviewed. Stone composition
      and initial 24-h urine collections (24-h urinary volumes, pH, calcium, sodium,
      uric acid, oxalate, citrate, and the number of abnormalities/patient per
      collection) were compared with 20 randomly selected stone-forming patients
      (controls) with no known anatomical abnormalities. Stone formation rates before
      and after the start of medical therapy were calculated in the patients available
      for follow-up. RESULTS: Twelve of the diverticulum patients (five men and seven
      women) had complete 24-h urine collections, all of whom had at least one
      metabolic abnormality. Seven patients had hypercalciuria, four had
      hyperuricosuria and three had mild hyperoxaluria. The most common abnormality was
      a low urine volume; 11 of the 12 patients had urine volumes of <2000 mL/day
      (range 350-1950). Ten patients had hypocitraturia in at least one of the two 24-h
      urine samples; seven had low urinary citrate levels (172-553 mg/day) on both
      samples. The findings were similar in the control group. The diverticulum
      patients had 3.1 abnormalities/patient, and the controls had 2.9
      abnormalities/patient (P > 0.05). No patients had gouty diathesis and none
      developed cystine stones. Stone analyses were similar in the two groups; both
      developed either calcium oxalate or mixed calcium oxalate/calcium phosphate
      stones. Six patients were followed for a mean of 23.1 months while on selective
      medical therapy; only one passed any additional stones, thought to be existing
      calculi, for a remission rate of five of six (83%). CONCLUSIONS: All patients
      with symptomatic calyceal diverticular stones who had comprehensive metabolic
      evaluation had metabolic abnormalities. There were similar abnormalities in the
      control random stone-formers. The abnormalities were corrected with selective
      medical therapy, as shown by the high remission rate. We recommend that, for
      patients with symptomatic calyceal diverticular calculi, a metabolic evaluation
      should be considered to determine stone forming risk factors.

PMID- 16643492
TI  - A randomized study comparing an antireflux system with a direct ureteric
      anastomosis in patients with orthotopic ileal neobladders.
AB  - OBJECTIVE: To assess the benefit of an antireflux system in patients with
      orthotopic ileal neobladders, as there is controversy about whether reflux
      prevention offers any advantages. PATIENTS AND METHODS: We conducted a randomized
      prospective study between January 2002 and March 2004, on 60 patients (53 men and
      seven women) with a mean (sd) age of 52.7 (7.3) years, who were candidates for
      orthotopic neobladders. Patients with comorbidities were excluded. Preoperative
      evaluation included intravenous urography (IVU), cystoscopic biopsy and
      radioisotope renography to evaluate the differential glomerular filtration rates
      (GFRs). Cases with normal kidneys and ureters, and with similar GFRs, were
      enrolled. Surgery comprised a standard radical cystectomy with pelvic
      lymphadenectomy. The ureters were randomized to either a direct anastomosis into
      a 5-cm ileal chimney on one side, or to be implanted using the antireflux serous
      lined extramural tunnel on the contralateral side in the same patient. Regular
      follow-up included IVU and renography every 6 months in cancer-free patients.
      RESULTS: The mean (sd) follow-up was 23 (9.6) months. There was prolonged urinary
      leak from a refluxing ureter in one patient that was treated with a temporary
      percutaneous nephrostomy. Symptomatic pelvic collections required tube drainage
      in six cases. Six ureters developed early anastomotic strictures (one direct and
      five antirefluxing), and were treated with endoscopic ureterotomy in three and
      open revision in three. Serum creatinine levels were normal in all patients
      throughout the observation period. GFRs were similar in the two groups. The mean
      GFRs before surgery and at 6, 12, 18, and 24 months after cystectomy were: 55.1,
      50.7, 49.4, 52.2 and 53.9 mL/min for the direct side; and 56.1, 53, 52.4, 53.2
      and 50.4 mL/min for renal units with antirefluxing implantation. There was a
      significant deterioration of the GFRs due to anastomotic strictures, from 48.6
      (6.7) mL/min before surgery to 31.8 (15.9) mL/min after the revision (P = 0.01).
      CONCLUSIONS: The antireflux procedures were associated with a higher incidence of
      anastomotic strictures than the direct methods and there was a significant
      deterioration of renal function after obstruction. The long-term follow-up data
      are awaited.

PMID- 16643493
TI  - Predictive factors of resolution of primary vesico-ureteric reflux: a
      multivariate analysis.
AB  - OBJECTIVE: To identify independent factors predicting the resolution of primary
      vesico-ureteric reflux (VUR) in a cohort of medically managed children. PATIENTS
      AND METHODS: Between 1977 and 2003, 506 children were diagnosed with VUR and were
      conservatively managed and prospectively followed. All of the children were
      maintained on antibiotic prophylaxis. Follow-up imaging consisted of voiding
      cysto-urethrography (VCUG) or a direct isotope cystogram at intervals of 2-3
      years. The predictive factors used are based on the patient data at the time of
      entry in the protocol. The dependent variable was VUR resolution. The criterion
      for resolution was based on a single negative VCUG or direct isotope cystogram. A
      survival analysis identified variables significantly associated with VUR
      resolution. Cox's regression model was applied to identify variables
      independently associated with the dependent variable. RESULTS: After adjustment,
      four variables remained as independent predictors of VUR resolution: nonwhite
      race, relative risk (95% confidence interval) of 1.5 (1.1-1.9; P = 0.009); mild
      grade of VUR, 3.3 (2.1-5.3; P < 0.001); absence of renal damage, 3.3 (2.4-4.5; P
      < 0.001); and absence of dysfunctional voiding, 2.0 (1.4-3.1; P < 0.001). For
      mild VUR, three variables were significantly associated: male gender, 1.7 (1.1
      2.6; P = 0.012); absence of renal damage, 3.4 (1.8-6.4; P < 0.001); and
      unilateral VUR, 1.6 (1.1-2.3; P = 0.004). For moderate/severe VUR, three
      variables were significantly associated: nonwhite race, 1.7 (1.1-2.6; P = 0.01);
      absence of renal damage, 3.0 (2.0-4.4; P < 0.001); and absence of dysfunctional
      voiding, 2.8 (1.4-5.5; P = 0.004). CONCLUSION: Few factors are amenable to
      intervention to modify the natural history of VUR. According to our findings,
      there are only two possible interventions: avoiding renal scars and managing
      voiding dysfunction.

PMID- 16643494
TI  - Differences in characteristics of nocturnal enuresis between children and
      adolescents: a critical appraisal from a large epidemiological study.
AB  - OBJECTIVE: To evaluate any differences in the characteristics of primary
      nocturnal enuresis (PNE) between younger enuretic children and adolescents.
      SUBJECTS AND METHODS: In all, 21 000 questionnaires designed to determine the
      presence or absence of bed-wetting, diurnal incontinence, frequency of wetting,
      systemic illness, and family history, were sent to children aged 5-19 years from
      67 kindergartens, primary schools and secondary schools randomly selected by a
      computer from different areas in Hong Kong. In addition, questions were asked to
      evaluate when and how the parents became aware that bed-wetting is a significant
      medical problem deserving attention in children after the age of 5 years.
      RESULTS: Of the 21,000 questionnaires distributed, 16 512 (78.6%) were completed.
      Among the respondents, 512 children (302 boys, 210 girls) had PNE; of these, 106
      (20.7%) also had daytime incontinence. There was a marked reduction in the
      overall prevalence of PNE with advancing age. At 5 years old, 16.1% of children
      had PNE (20.7% boys, 10.8% girls; at age 9 and 19 years, 3.14% and 2.2% of
      children had PNE, respectively. However, this reduction was significantly more
      apparent among those with mild enuretic symptoms (wet <3 nights/week) than in
      those with more frequent bed-wetting. Furthermore, younger enuretic children
      behaved very differently from adolescents and older patients. As age increased
      there was a significant tendency towards more severe enuretic symptoms. At age 5
      years, 14.3% of enuretic children wet 7 nights/week, compared with 48.3% at age
      19 years (P < 0.001). In addition, significantly more adolescent boys aged >10
      years had daytime urinary incontinence than had enuretic children aged < or = 10
      years (32% vs 14.6%, respectively, P < 0.001). Most (89%) parents only became
      aware that bed-wetting was a significant medical problem deserving attention
      through material in the mass media over the past 3-4 years. CONCLUSIONS: The
      present finding suggesting that PNE spontaneously resolves with increasing age
      probably applies only to those with mild enuretic symptoms. There are significant
      differences in characteristics between younger enuretic children and older
      subjects. As age increases there is an increasing proportion of enuretic patients
      with more severe bed-wetting. Enuretic children aged >10 years and adolescents
      have significantly more daytime urinary symptoms and incontinence. The previously
      reported low prevalence of PNE in Hong Kong was probably due to parental
      indifference to the problem.

PMID- 16643495
TI  - Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function
      in the same rat in vivo.
AB  - OBJECTIVE: To establish the methods, feasibility and utility of evaluating the
      impact of diabetes on bladder and erectile function in the same rat, as more than
      half of diabetic patients have bladder dysfunction, and half of diabetic men have
      erectile dysfunction, but the severity of coincident disease has not been
      rigorously assessed. MATERIALS AND METHODS: In all, 16 F-344 rats had diabetes
      induced by streptozotocin (STZ), and were divided into insulin-treated (five) and
      untreated (11), and compared with age-matched controls (10), all assessed in
      parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were
      conducted on all rats, with cavernosometric studies conducted on a subset of
      rats. RESULTS: There were insulin-reversible increases in the following
      cystometric variables; bladder weight, bladder capacity, micturition volume,
      residual volume, micturition pressure and spontaneous activity (P < 0.05, in all,
      one-way analysis of variance, anova). Cavernosometry showed a diabetes-related,
      insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal
      pressure (ICP) response at all levels of current stimulation (P < 0.05, in all
      one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity
      showed no correlation between the extent of the decline in erectile capacity and
      the magnitude of the increase in bladder capacity. CONCLUSIONS: These studies
      extend previous work to indicate that the extent of diabetes-related bladder and
      erectile dysfunction can vary in the same rat. As such, these findings highlight
      the importance of evaluating the impact of diabetes on multiple organ systems in
      the lower urinary tract. Future studies using this model system should lead to a
      better understanding of the initiation, development, progression and coincidence
      of these common diabetic complications.

PMID- 16643496
TI  - The influence of changes in extracellular and intracellular sodium concentration
      on detrusor contractility.
AB  - OBJECTIVE: To determine the role of Na+-Ca2+ exchange in the regulation of
      isolated detrusor smooth muscle contractility. MATERIALS AND METHODS: Isolated
      guinea-pig detrusor strips were used to record isometric tension generated by;
      (a) electrical-field stimulation to elicit nerve-mediated responses; and (b)
      adding carbachol or superfusing with a high-K+ solution. The [Na+] gradient
      between extracellular and intracellular compartments was altered by: (i) reducing
      superfusate [Na+] in stages from 140.2 to 10.2 mm; (ii) addition of the cardiac
      glycoside strophanthidin (200 microm). RESULTS Reducing extracellular [Na+]
      reversibly reduced the magnitude of nerve-mediated contractions but increased the
      resting tension and magnitude of carbachol-induced contracture. The mean (sd)
      [Na+] required for a half-maximum effect on attenuating contractions, at 85.9
      (6.2) mm, and developing contracture, at 59.1 (14.3) mm, were significantly
      different. The time constants of changes to nerve-mediated contractions and
      carbachol contracture were also significantly different, at 147 (5) vs 1207 (386)
      s, respectively. These differences suggest that separate mechanisms influence
      nerve-mediated contraction and contracture in low-Na+ solutions. Exposure to the
      cardiac glycoside strophanthidin produced a similar effect to low-Na+ solutions
      for carbachol contracture. Low-Na+ solutions had no significant effect on
      contractures induced by high extracellular [K+]. CONCLUSION Reducing the
      transmembrane [Na+] difference increases intracellular [Ca2+]. This increase is
      largely accommodated in intracellular stores, that can be released by exogenous
      carbachol. The results are consistent with the presence of a functional Na+-Ca2+
      exchanger in the surface membrane. The lack of effect of low-Na+ solutions on
      contractures evoked by membrane depolarization is consistent with this
      conclusion. The reduction of the nerve-mediated contraction by low-Na+ solution
      might result from blockade of the nerve action potential.

PMID- 16643497
TI  - Physiological fatigue of smooth muscle contractions in rat urinary bladder.
AB  - OBJECTIVE: To characterize the physiological fatigue in bladder smooth muscles
      that can occur within 60 s of stimulation, which is closer to the duration of
      normal voiding. MATERIALS AND METHODS: Longitudinal and transverse strips of rat
      bladder were used; the muscles were mounted in an in vitro multi-muscle chamber,
      and the decline in contractile tension recorded during continuous electrical
      stimulation at frequencies of 5-30 Hz for 60 s. The effect of muscle length on
      fatigue was assessed by monitoring the decline in tension during 30 Hz
      stimulation at rest length, and at 60% and 100% stretched lengths of the bladder
      strips. To assess some of the factors involved in the development of fatigue,
      tension responses of fatigued muscles were monitored on exposure to 80 mm
      potassium or 1 microm bethanechol. RESULTS: In both longitudinal and transverse
      bladder strips stimulated at 30 Hz, peak contractile tension declined to 50% of
      original after approximately 33 s, and to 30% after 60 s of stimulation. After 10
      s rest, 60% of the original tension was recovered. Increasing the frequency of
      fatigue stimulation from 5 to 30 Hz significantly increased the extent of the
      decline in tension and reduced the time to a 50% decrease in tension. Stretching
      the bladder strips from rest length to 100% stretched length significantly
      reduced the extent of tension decline and increased the time to a 50% decrease in
      tension. Exposure of fatigued muscles to high potassium or bethanechol generated
      more tension than electrical stimulation. CONCLUSION: Contractile fatigue occurs
      in both longitudinal and transverse strips of the bladder smooth muscles within
      the duration of normal voiding. Increasing the frequency of stimulation from 5 to
      30 Hz increased the degree and rate of fatigue. Stretching the bladder strips
      from rest length by 60-100% reduced the degree and rate of fatigue. Bladder
      fatigue may be caused by decreased depolarization of the smooth muscle membranes,
      reduced release of acetylcholine from presynaptic nerve terminals, or by other
      yet undetermined mechanisms.

PMID- 16643498
TI  - Phasic non-micturition contractions in the bladder of the anaesthetized and awake
      rat.
AB  - OBJECTIVE: To characterize the contractile activity that occurs in the bladder
      during the filling phase of the micturition cycle (non-micturition contractions,
      NMCs), which generate transient rises in intravesical pressure not associated
      with urine flow. MATERIALS AND METHODS: The experiments were conducted using
      anaesthetized (chloral hydrate) and un-anaesthetized rats. In un-anaesthetized
      rats bladder contractile activity was measured using an intravesical cannula
      implanted under full surgical anaesthesia 3 days previously. In the anaesthetized
      rats the bladder was exteriorized and a cannula inserted through the dome. In
      these experiments electrical activity within the detrusor was also measured with
      a suction electrode on the bladder surface. For each rat, the experimental
      protocol involved filling the bladder at a constant rate (10 mL/h) to evoke
      micturition cycles, or infusion of a fixed volume and recording made under
      effective isovolumetric conditions. RESULTS: In both anaesthetized and un
      anaesthetized rats there were transient rises in bladder pressure (0.5-3 cmH2O).
      In the anaesthetized rats the amplitude of the transients increased throughout
      the filling phase, with little change in frequency. The phasic NMCs generating
      these pressure transients were accompanied by electrical changes in the detrusor.
      In the middle phase of bladder filling the slow pressure changes were accompanied
      by slow waves of electrical activity which changed in the pressure cycles
      immediately before micturition to high-frequency low-amplitude signals. In the un
      anaesthetized rats there was a period immediately after voiding where there was
      no activity. As filling proceeded, low-amplitude low-frequency NMCs appeared that
      gradually increased in frequency and amplitude during the filling phase. However,
      the frequency of the transients decreased immediately before micturition despite
      an increase in amplitude. Similar responses were seen during isovolumetric
      recording. CONCLUSION: The present results show the presence of NMCs in the rat
      bladder, identify volume-dependent changes in the pattern of this activity during
      the micturition cycle, and show that NMCs are accompanied by electrical changes
      in the detrusor. The physiological significance of NMCs is not known but it might
      be linked to the generation of afferent discharge from mechanoreceptors in the
      wall, so contributing to sensations related to bladder volume.

PMID- 16643499
TI  - Different isoform patterns for vascular endothelial growth factor between clear
      cell and papillary renal cell carcinoma.
AB  - OBJECTIVE: To investigate the protein expression of vascular endothelial growth
      factor (VEGF) isoforms in relation to the clinical course in patients with
      different renal cell carcinoma (RCC) types, as angiogenesis is essential for
      tumour growth and metastasis. PATIENTS AND METHODS: Western blots were assayed of
      protein extracts from tumour and concomitant kidney cortex samples from 96
      patients. The levels of VEGF189, VEGF165, and VEGF121 isoforms were correlated
      with clinicopathological characteristics and survival. RESULTS: VEGF189 levels
      were significantly higher in kidney cortex and chromophobe RCC than in papillary
      and conventional RCC. In papillary RCCs, VEGF189 levels correlated inversely with
      tumour stage and tumour size. VEGF165 levels were higher in kidney cortex than in
      RCC, but there was no difference among the RCC types. VEGF121 expression was
      associated with less advanced tumour stage in conventional RCC. Using
      multivariate analysis, VEGF189 remained as an independent prognostic factor for
      patients with papillary RCC. CONCLUSIONS: VEGF189 was associated with tumour
      progression; in papillary RCC, VEGF189 was a significant independent prognostic
      factor. VEGF protein isoform patterns differed among the specific RCC types.
      Additional knowledge is essential to design new anti-angiogenic therapies for all
      RCC types.

PMID- 16643500
TI  - Diagnostic utility of a p63/alpha-methyl coenzyme A racemase (p504s) cocktail in
      ambiguous lesions of the prostate upon needle biopsy.
AB  - OBJECTIVE: To investigate the potential utility of a new combined immunostaining
      technique for diagnosing prostate cancer from histological analysis of needle
      biopsy specimens. MATERIALS AND METHODS: Tissue was immunostained with a
      combination of antibodies against a basal cell marker (p63), and an enzyme
      commonly overexpressed in prostate cancer (p504s), on 63 small prostate cancer
      foci (<1 mm) and 109 cases of ambiguous lesions observed in needle biopsies.
      RESULTS: After p63/p504s immunostaining, 93% of the ambiguous lesions (102/109)
      were classified. The final diagnoses retained were: 92 prostate cancers, seven
      atypical small acinar proliferations suspected of being malignant but
      undiagnosed, 21 prostatic intraepithelial neoplasia, five atypical adenomatous
      hyperplasia, and 36 atrophic benign mimickers of cancer. CONCLUSIONS: Combining
      p504s as a positive marker for prostate cancer and p63 as a negative marker might
      improve diagnostic performance, sensitivity and specificity, and lead to fewer
      false-negative results. This simple immunostaining procedure should reduce the
      percentage of residual ambiguous lesions and the need for additional biopsies.

PMID- 16643501
TI  - The effects of human chorionic gonadotrophin on normal testicular tissue of rats:
      dose-dependence and reversibility.
AB  - OBJECTIVE To investigate the effect of human chorionic gonadotrophin (hCG) on rat
      testicular tissue, and its reversibility and dose dependence. MATERIALS AND
      METHODS Male Wistar rats were assigned to groups (10 rats/group) receiving 10, 30
      or 50 IU/kg hCG subcutaneously once daily for 15 days; 10 controls received
      subcutaneous isotonic saline. At 1 and 3 months later, five rats in each group
      were killed and their testes removed. The testes were examined histologically to
      measure seminiferous tubular diameter and germinal membrane thickness. RESULTS At
      1 month after hCG administration, the mean germinal membrane thickness in the
      testicular tissues of the hCG-treated rats was significantly less than in control
      rats, and was also significantly different between all of the hCG-treated groups
      (P < 0.05). However, at 3 months after hCG administration, all histological
      variables were similar to those in control rats (P > 0.05), and the mean germinal
      membrane thickness at 3 months after hCG administration was larger than that at 1
      month (P < 0.05). There were no significant differences in the mean seminiferous
      tubular diameter between hCG-treated rats and control rats. CONCLUSION hCG
      impairs seminiferous tubule histology in the 'normal' descended testes of rats.
      This effect was dose-dependent, and the changes were reversed at 3 months after
      treatment. Thus, although hCG therapy might affect the seminiferous tubules of
      contralateral descended testes in cryptorchid boys, these effects might be
      reversible.

PMID- 16643502
TI  - Another year, another AUA.

PMID- 16643503
TI  - Perianal and intrarectal anaesthesia for transrectal biopsy of the prostate: a
      prospective randomized study comparing lidocaine-prilocaine cream and placebo.

PMID- 16643504
TI  - A case for screening for renal cancer.

PMID- 16643505
TI  - Proteinuria on dipstick urine analysis after sexual intercourse.

PMID- 16643506
TI  - Surgical atlas: anastomotic urethroplasty.

PMID- 16643507
TI  - A case for screening for renal cancer.

PMID- 16643508
TI  - A case for screening for renal cancer.

PMID- 16643509
TI  - Surgical atlas. Surgical management of penile carcinoma: the inguinal nodes.

PMID- 16643511
TI  - Spatial learning induces predominant downregulation of cytosolic proteins in the
      rat hippocampus.
AB  - Spatial learning is known to depend on protein synthesis in the hippocampus.
      Whereas the role of the hippocampus in spatial memory is established, the
      biochemical and molecular mechanisms underlying this process are poorly
      understood. To comprehend the complex pattern of protein expression induced by
      spatial learning, we analyzed alterations in the rat hippocampus proteome after 7
      days of spatial learning in the Morris water maze. Forty Wistar rats were
      randomized into two groups. Animals of group A learned to localize a hidden
      platform in the water maze. Animals of group B served as controls and spent
      exactly the same time in the water maze as animals of group A. However, no
      platform was used in this test and the rats could not learn to localize the
      target. After the last trial, hydrophilic proteins from the hippocampus were
      isolated. A proteome-wide study was performed, based on two-dimensional gel
      electrophoresis and mass spectrometry. Compared with non-learning animals, 53
      (70%) proteins were downregulated and 23 (30%) proteins were upregulated after 7
      days in rats with spatial learning. The overall changes in protein expression, as
      quantified by the induction factor, ranged from -1.62 (downregulation to 62%) to
      2.10 (upregulation by 110%) compared with controls (100%). Most identified
      proteins exhibit known functions in vesicle transport, cytoskeletal architecture,
      and metabolism as well as neurogenesis. These findings indicate that learning in
      the Morris water maze has a morphological correlate on the proteome level in the
      hippocampus.

PMID- 16643512
TI  - Defining the dopamine transporter proteome by convergent biochemical and in
      silico analyses.
AB  - Monoamine transporters play a key role in neuronal signaling by mediating
      reuptake of neurotransmitters from the synapse. The function of the dopamine
      transporter (DAT), an important member of this family of transporters, is
      regulated by multiple signaling mechanisms, which result in altered cell surface
      trafficking of DAT. Protein-protein interactions are likely critical for this
      mode of transporter regulation. In this study, we identified proteins associated
      with DAT by immunoprecipitation (IP) followed by mass spectrometry. We identified
      20 proteins with diverse cellular functions that can be classified as trafficking
      proteins, cytoskeletal proteins, ion channels and extracellular matrix-associated
      proteins. DAT was found to associate with the voltage-gated potassium channel
      Kv2.1 and synapsin Ib, a protein involved in regulating neurotransmitter release.
      An in silico analysis provided evidence for common transcriptional regulation of
      the DAT proteome genes. In summary, this study identified a network of proteins
      that are primary candidates for functional regulation of the DAT, an important
      player in mechanisms of mental disorders and drug addiction.

PMID- 16643514
TI  - Escherichia coli native valve endocarditis.
AB  - Among 36 cases of Escherichia coli native valve endocarditis (NVE) that met Duke
      criteria (31 cases in the literature between 1909 and 2002, and five cases seen
      in Paris, France), the urinary tract was the most common portal of entry. The
      majority (72.2%) of cases developed in elderly females. Overall, the proportion
      of patients aged > 70 years rose from 5.3% in 1982 to 22.9% in 2002. Persistent
      E. coli bacteraemia in the elderly in the absence of cardiac risk-factors may be
      a sign of NVE and should prompt an investigation by echocardiography.

PMID- 16643515
TI  - Role of the dual interaction of fungal pathogens with pattern recognition
      receptors in the activation and modulation of host defence.
AB  - Recognition of pathogen-associated molecular patterns (PAMPs) of microorganisms
      by pathogen recognition receptors induces signals responsible for the activation
      of genes important for an effective host defence, especially those of pro
      inflammatory cytokines. Toll-like receptors (TLRs) and lectin-like receptors are
      the most important classes of pattern-recognition receptors. In addition to their
      effects on the activation of host defence, recent studies suggest that pathogenic
      fungi can modulate or interfere with the pattern recognition mechanisms of innate
      immunity, and can use pattern recognition receptors as mechanisms of escape from
      host defence. Two major recognition receptor-mediated escape mechanisms have been
      identified during infection with fungal pathogens: immunosuppression induced by
      activation of certain pattern recognition receptors, especially induction of IL
      10 release through TLR2; and the blockade of TLR recognition by antigen
      modification during the germination of yeasts into hyphae. Thus, signals mediated
      by recognition receptors are not only beneficial to the host, but in certain
      situations can be used by pathogenic fungi to escape immune recognition and
      promote infection.

PMID- 16643516
TI  - Priorities for antibiotic resistance surveillance in Europe.
AB  - Antibiotic resistance is an increasing global problem. Surveillance studies are
      needed to monitor resistance development, to guide local empirical therapy, and
      to implement timely and adequate countermeasures. To achieve this, surveillance
      studies must have standardised methodologies, be longitudinal, and cover a
      sufficiently large and representative population. However, many fall short of
      these requirements that define good surveillance studies. Moreover, current
      efforts are dispersed among many, mostly small, initiatives with different
      objectives. These studies must be tailored to the various reservoirs of
      antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the
      community, animals and food. Two studies that could serve as examples of tailored
      programmes are the European Antimicrobial Resistance Surveillance System (EARSS),
      which collects resistance data during the diagnosis of hospitalised patients, and
      the DANMAP programme, which collects data in the veterinary sector. As already
      noted by the WHO, genetic studies that include both the typing of isolates and
      the characterisation of resistance determinants are necessary to understand fully
      the spread and development of antibiotic resistance.

PMID- 16643517
TI  - Statistical characterisation of bacterial wild-type MIC value distributions and
      the determination of epidemiological cut-off values.
AB  - MIC distribution data were obtained from a variety of international sources, and
      pooled after selection by a defined criterion. Sixty-seven of these datasets were
      subjected to a range of statistical goodness-of-fit tests. The log-normal
      distribution was selected for subsequent modelling. Cumulative counts of MIC
      distribution data were fitted to the cumulative log-normal distribution using non
      linear least squares regression for a range of data subsets from each antibiotic
      bacterium combination. Estimated parameters in the regression were the number of
      isolates in the subset, and (the log(2) values of) the mean and standard
      deviation. Optimum fits for the cumulative log-normal curve were then used to
      determine the wild-type MIC range, determined by calculating the MICs associated
      with the lower and upper 0.1% of the distribution, rounding to the nearest two
      fold dilution, and calculating the probabilities of values higher and lower than
      these values. When plotted logarithmically, histograms of MIC frequencies
      appeared normal (Gaussian), but standard goodness-of-fit tests showed that the
      two-fold dilution grouping of MICs fits poorly to a log-normal distribution,
      whereas non-linear regression gave good fits to population (histogram) log-normal
      distributions of log(2) MIC frequencies, and even better fits to log-normal
      cumulative distributions. Optimum fits were found when the difference between the
      estimated and true number of isolates in the fitted subset was minimal. Sixteen
      antibiotic-bacterium datasets were fitted using this technique, and the log(2)
      values of the means and standard deviations were used to determine the 0.1% and
      99.9% wild-type cut-off values. When rounded to the nearest two-fold dilution, >
      or = 98.5% of MIC values fall within the cut-off value range. Non-linear
      regression fitting to a cumulative log-normal distribution is a novel and
      effective method for modelling MIC distributions and quantifying wild-type MIC
      ranges.

PMID- 16643518
TI  - In-vivo impact of the MexXY efflux system on aminoglycoside efficacy in an
      experimental model of Pseudomonas aeruginosa pneumonia treated with tobramycin.
AB  - Aminoglycosides are of major importance in treating Pseudomonas aeruginosa
      pneumonia (PAP). However, their efficacy may be compromised by low-level
      resistance caused by the inducible MexXY multidrug efflux pump. In the present
      study, the impact of the MexXY efflux pump was investigated in vivo in an
      experimental model of PAP in rabbits treated with intravenous tobramycin. Three
      strains were used to induce PAP in rabbits: PAO1 (wild-type strain; MIC 1 mg/L),
      mutant 11B (mexX::Tn501; no expression of MexXY; MIC 0.5 mg/L) and mutant MutGR1
      (MexZ null; constitutive expression of MexXY; MIC 2 mg/L). Five hours after
      inoculation, treatment with tobramycin (10 mg/kg) was implemented (peak serum
      concentration 30 mg/L). The animals were killed humanely 48 h after inoculation,
      and the residual pulmonary bacterial concentration was determined. Selection of
      bacteria expressing MexXY was determined by plating lung homogenates on agar
      plates containing antibiotic. Mean bacterial counts (log(10) CFU/g) for treated
      vs. untreated rabbits were 6.26 and 8.13 (p < 0.0001), 6.00 and 8.38 (p < 0.001),
      and 7.25 and 8.79 (p 0.04) for PAO1, 11B and MutGR1, respectively, with an
      overall mortality rate of 0% vs. 8.9% (p < 0.01). MexXY-overexpressing bacteria
      were recovered from three (21%) treated rabbits. The C(max)/MIC ratio was the
      parameter that was best associated with tobramycin efficacy. The bacteria
      overexpressing MexXY, recovered from lung, occurred with a C(max)/MIC window of
      19-26. It was concluded that the experimental PAP model highlights poor
      tobramycin bacteriological efficacy in vivo, contrasting with survival gain, and
      that the contribution of the MexXY system to this low level of tobramycin
      efficacy is modest. Finally, this model appears to be suitable for the
      investigation of new anti-pseudomonal therapeutic strategies.

PMID- 16643519
TI  - Outcome of prosthetic knee-associated infection: evaluation of 40 consecutive
      episodes at a single centre.
AB  - Few studies have compared the long-term success of different surgical strategies
      in prosthetic knee-associated infection. Accordingly, a retrospective cohort
      study was performed of 40 episodes in 35 consecutive patients undergoing revision
      surgery for prosthetic knee-associated infection at a single centre between 1988
      and 2003. The median patient age was 70 (44-90) years; the median follow-up
      period was 28 (2-193) months; 45% of infections were early, 23% were delayed, and
      32% were late; and 55% of infections were caused by staphylococci. The
      probability of survival without prosthesis failure was 92.4% (95% CI, 84.1-100)
      after 1 year, and 88.7% (95% CI, 78-99.4) after 2 years. Recurrence-free survival
      was observed in 20 (95%) of 21 patients treated with debridement and retention,
      in both patients with one-stage exchange, and in 11 (85%) of 13 patients with two
      stage exchange. Patients with delayed infection had a worse outcome than those
      with early or late infection (67% vs. 97%; p < 0.03). Patients with at least
      partially adequate antimicrobial therapy had a higher success rate than those
      with inadequate treatment (94% vs. 60%; p 0.069). The outcome was similar for
      patients with a duration of therapy of 3 to < 6 months, and those with a duration
      of therapy of > or = 6 months (91% vs. 87% success). Different surgical
      procedures had similar success rates, provided that the type of infection, the
      pathogen, the stability of the implant and the local skin and soft-tissue
      condition were considered. Adherence to an algorithm defining a rational surgical
      and antibiotic treatment strategy contributed to a favourable outcome.

PMID- 16643520
TI  - Correlation of quinolone resistance levels and differences in basal and quinolone
      induced expression from three qnrA-containing plasmids.
AB  - This study investigated the effect of copy number and transcriptional level of
      the qnrA gene on plasmid-mediated quinolone resistance, and the effect of
      quinolones on qnrA expression, in three clinical isolates of Klebsiella
      pneumoniae and the corresponding Escherichia coli transconjugants. The copy
      number of plasmids containing qnrA was analysed and transcriptional studies were
      performed on transconjugants grown in the presence or absence of ciprofloxacin or
      moxifloxacin. None of the three clinical isolates was porin-deficient. One
      isolate contained a mutation in the quinolone resistance-determining region of
      the gyrA gene (Ser83Phe), but no gyrA mutations were present in the other two
      isolates, and no mutations were found in parC. Differences in qnrA copy number
      were observed in K. pneumoniae, but not in the corresponding E. coli
      transconjugants, although the qnrA gene was located in plasmids with similar
      mobility and Southern blot RFLP pattern. Differences in qnrA transcription, both
      at the basal level and following induction by quinolones, were observed among
      transconjugants. Expression of the qnrA gene correlated well with the level of
      quinolone (ciprofloxacin and moxifloxacin) resistance in E. coli transconjugants.
      These data suggest that the main factor determining the resistance level in the
      transconjugants analysed was the different levels of qnrA expression.

PMID- 16643521
TI  - Assessment of ica operon carriage and biofilm production in Staphylococcus
      epidermidis isolates causing bacteraemia in bone marrow transplant recipients.
AB  - The clinical significance of coagulase-negative staphylococci isolated from blood
      culture is typically assessed on the basis of a combination of clinical and
      microbiological criteria. However, these criteria are difficult to apply to
      haematology patients who are highly immunosuppressed and from whom blood cultures
      are obtained most frequently through a central venous catheter. This study
      analysed 112 episodes of Staphylococcus epidermidis bacteraemia that occurred in
      79 bone marrow transplant recipients. In 73 (65%) episodes, only one blood
      culture set was positive for S. epidermidis, while 39 (35%) episodes grew S.
      epidermidis from multiple blood cultures. Nine patients had two or more episodes
      of bacteraemia with the same strain, as determined by pulsed-field gel
      electrophoresis (PFGE). The PFGE method also showed that 34 (31%) isolates
      belonged to seven clusters, indicating the persistence of certain clones in the
      environment. Of the 109 isolates analysed, 59 (54%) produced biofilm and 91
      (83.5%) carried the ica operon. Isolates that produced biofilm were observed to
      colonise central venous catheters faster than non-biofilm-producing isolates (18
      vs. 37 days; p 0.03). No clinical features were associated with carriage of the
      ica operon, but the ica operon was carried more frequently by the isolates that
      formed clusters.

PMID- 16643522
TI  - Seropositivity to a major allergen of Anisakis simplex, Ani s 1, in dyspeptic
      patients with Helicobacter pylori infection: histological and laboratory findings
      and clinical significance.
AB  - Previous studies have demonstrated a high prevalence of seropositivity to the Ani
      s 1 protein in dyspeptic patients with Helicobacter pylori infection, but it is
      not known whether this represents episodes of anisakiasis misdiagnosis or
      previous exposure to the parasite without clinical relevance. To investigate the
      clinical significance of seropositivity to the Ani s 1 protein, a cohort study
      was performed with 87 consecutive dyspeptic patients who were treated for H.
      pylori infection. Fourteen (16.5%) patients were seropositive for the Ani s 1
      protein, which was associated with the consumption of uncooked fish (p 0.0002).
      There were no differences in histological findings between subjects seropositive
      or seronegative for Ani s 1, but seropositive patients had increased eosinophil
      and basophil leukocyte counts (p < 0.05). Anti-Ani s 1 IgE was associated with a
      lack of improvement in the group of patients with non-ulcer dyspepsia after
      successful eradication of H. pylori (p 0.016). Thus, in at least a subset of
      patients with H. pylori infection, seropositivity to Ani s 1 could have clinical
      relevance. In addition, these data highlight that only anisakiasis associated
      with severe allergic or gastric symptoms is currently being diagnosed.

PMID- 16643523
TI  - Lack of specificity of a single positive 50-kDa band in the electroimmunotransfer
      blot (EITB) assay for cysticercosis.
AB  - Diagnosis of the parasitic infection cysticercosis is usually confirmed by
      serological assays. The electroimmunotransfer blot (EITB) for cysticercosis is a
      sensitive and specific assay, which uses six glycoprotein antigens on a strip to
      detect antibodies to Taenia solium cysticerci. Although the appearance of bands
      at any of these six sites is considered to be a positive result, a growing body
      of evidence suggests that the presence of a single 50-kDa band in this assay may
      not indicate infection. An audit of 984 samples tested over a 3-year period
      showed that only two (15.4%) of 13 samples with a single 50-kDa band were
      associated with a diagnosis of cysticercosis. Possible reasons for this include
      technical problems, cross-reactivity with other parasites or other diseases, or
      the presence of a non-specific band. The results suggest that the finding of a
      single 50-kDa band should be interpreted with caution.

PMID- 16643524
TI  - Performance of a novel test for IgM and IgG antibodies in subjects with culture
      documented genital herpes simplex virus-1 or -2 infection.
AB  - Novel tests (BioPlex) for herpes simplex virus-1 (HSV-1) and HSV-2 IgG were
      compared with HerpeSelect HSV-1 and HSV-2 ELISAs for type-specific IgG. The
      sensitivity and specificity of BioPlex HSV-1 IgG were 94% (84/89) and 96%
      (119/124), respectively, with unselected sera, while the sensitivity and
      specificity of BioPlex HSV-2 IgG were 92% (109/118) and 98% (95/97),
      respectively. BioPlex IgM was compared with Diamedix IgM against sera from
      patients with culture-documented genital herpes. The test results were concordant
      in 81% of sera from HSV-1 patients and in 90% of sera from HSV-2 patients. Use of
      BioPlex IgM in addition to BioPlex IgG tests increased HSV-2 seroconversion
      detection from 47% of subjects to 70%. Use of Diamedix IgM in addition to Focus
      IgG ELISA increased HSV-2 detection from 40% of subjects to 70%. IgM was detected
      by BioPlex in 63% of sera from patients with early HSV-2 infection (< 30 days)
      and in 59% of sera by Diamedix. IgM was also detected in a large proportion of
      sera from subjects with established HSV-2 infection (33% by BioPlex and 29% by
      Diamedix). Addition of IgM testing substantially increased the ability to detect
      seroconversion early in infection. IgM is an indicator of recent infection only
      in subjects who lack detectable IgG.

PMID- 16643525
TI  - Diagnostic value of an ELISA using a recombinant 54-kDa species-specific protein
      from Chlamydia pneumoniae.
AB  - The aim of this study was to evaluate a 54-kDa recombinant protein encoded by the
      CPn0980 gene for use in a Chlamydia pneumoniae-specific ELISA. The ability of
      this affinity-purified protein to detect C. pneumoniae-specific antibodies was
      evaluated with a panel of 105 serum samples from 62 patients with community
      acquired pneumonia. The results of this assay were compared with those obtained
      with a direct PCR-based detection assay and an outer-membrane complex-based
      immunoassay. The 54-kDa protein induced specific antibodies following infection
      of humans, and the recombinant 54-kDa ELISA detected anti-C. pneumoniae IgG
      and/or IgM antibodies with a sensitivity of 66.7% and a specificity of 79.2%
      compared with the direct PCR-based detection assay.

PMID- 16643526
TI  - The identification of mycobacteria from solid media and directly from VersaTREK
      Myco bottles using the Sherlock Mycobacteria Identification HPLC system.
AB  - The Sherlock Mycobacteria Identification HPLC system correctly identified to the
      species level 61 (67.8%) of 90 isolates growing on solid media, and 73 (45.3%) of
      161 isolates directly from positive VersaTREK Myco bottles. When these data were
      re-analysed with a revised database, correct identifications increased to 91.1%
      and 83.2%, respectively. All Mycobacterium tuberculosis isolates were identified
      correctly, regardless of the inoculum source or database used. The use of the
      revised database with isolates obtained directly from positive VersaTREK Myco
      bottles allows the identification of most isolates within clinically relevant
      time-frames.

PMID- 16643527
TI  - Evaluation of a novel strip test, GenoType Mycobacterium CM/AS, for species
      identification of mycobacterial cultures.
AB  - A novel DNA strip assay, GenoType Mycobacterium AS, was evaluated for its ability
      to identify 219 mycobacterial isolates in combination with the GenoType
      Mycobacterium CM assay. The results were compared with those obtained by
      conventional 16S rDNA sequencing. The Genotype test correlated well (96%) with
      sequencing. However, with the CM kit alone, it was possible to identify most
      (88%) of the isolates found in clinical specimens, and the AS kit provided very
      little additional information.

PMID- 16643528
TI  - Urease genes in non-O157 Shiga toxin-producing Escherichia coli: mostly silent
      but valuable markers for pathogenicity.
AB  - The distribution of ureC was investigated among 294 Escherichia coli isolates,
      comprising 72 strains from the E. coli standard reference collection (ECOR), 62
      strains from the diarrhoeagenic E. coli (DEC) collection, and 160 clinical
      isolates of Shiga toxin-producing E. coli (STEC). The ureC gene was more frequent
      among STEC isolates harbouring eae than among those lacking eae (p < 0.0001). All
      clinical STEC isolates of serogroups O111 and O145 contained ureC, but only two
      of 294 isolates expressed urease activity. The silencing of urease expression
      could not be linked to a stop codon in ureD. The frequent occurrence of ure genes
      in eae-positive STEC isolates makes them valuable markers for virulence.

PMID- 16643529
TI  - Efficacy and safety of an anti-retroviral combination regimen including either
      efavirenz or lopinavir-ritonavir with a backbone of two nucleoside reverse
      transcriptase inhibitors.
AB  - The efficacy and safety of a combination regimen including either efavirenz or
      lopinavir-ritonavir was examined in a cohort of 65 patients positive for human
      immunodeficiency virus-1 (HIV-1). Both the efavirenz (n = 33, 18 anti-retroviral
      naive) and lopinavir-ritonavir (n = 32, 15 naive) regimens achieved significant
      changes from baseline CD4 cell counts and HIV RNA levels after 108 weeks (p <
      0.01). Despite diminished immunological and virological parameters at study
      entry, the lopinavir-ritonavir group showed greater virological effects than the
      efavirenz group after 108 weeks (median change 3.3 log(10), interquartile range
      (IQR) 2.2-3.8 log(10) vs. 2.4 log(10), IQR 0.9-3.3 log(10), respectively, p
      0.004). Use of lopinavir-ritonavir, in contrast to use of efavirenz, was
      associated with significant hypertriglyceridaemia.

PMID- 16643530
TI  - Serotypes and antimicrobial susceptibilities of 1033 pneumococci isolated from
      children in Greece during 2001-2004.
AB  - Pneumococci (n = 1033) isolated in the major paediatric hospitals of Athens
      during 2001-2004 from children with invasive infections (n = 186), non-invasive
      infections (n = 641) and healthy carriers (n = 206) were studied. The most
      prevalent serotypes were serotypes 14 (44.6%), 19F (43.5%) and 6B (22.8%) in
      invasive, non-invasive and carriage isolates, respectively. Among invasive
      isolates, the potential coverage by the seven-valent conjugate vaccine was 75.3%.
      Resistance rates to penicillin, amoxycillin, cefotaxime, erythromycin, co
      trimoxazole, clindamycin, tetracycline and chloramphenicol were 44.6%, 2.7%,
      1.2%, 43.6%, 43.5%, 12.4%, 34.7% and 5.9%, respectively. The M-phenotype
      accounted for 68.0% of the erythromycin-resistant isolates. All isolates were
      susceptible to ofloxacin.

PMID- 16643531
TI  - Serological evidence of Rickettsia infections in forestry rangers in north
      eastern Italy.
AB  - The prevalence of antibodies to Rickettsiae and other tick-borne microrganisms in
      the sera of 181 forestry rangers from Friuli-Venezia-Giulia, Italy, was examined.
      Seven (3.9%) sera were positive for Rickettsia conorii and Rickettsia helvetica,
      as single or dual infections; four of these sera had been found previously to be
      positive for Borrelia burgdorferi. Antibodies to Coxiella burnetii were detected
      in five (2.8%) sera, four of which were also positive for B. burgdorferi. These
      findings indicate that patients in this north-eastern Italian region with fever
      subsequent to tick-bite should be investigated for Rickettsia and Coxiella
      infections.

PMID- 16643532
TI  - VlsE C6 peptide and IgG ELISA antibody analysis for clinical diagnosis of Lyme
      borreliosis in an endemic area.

PMID- 16643533
TI  - Bacteraemia in cancer patients caused by colistin-resistant Gram-negative bacilli
      after previous exposure to ciprofloxacin and/or colistin.

PMID- 16643534
TI  - The effect of implementing the British Thoracic Society community-acquired
      pneumonia guidelines on antibiotic prescribing and costs in a UK teaching
      hospital.

PMID- 16643535
TI  - The relationship between caries in the primary dentition at 5 years of age and
      permanent dentition at 10 years of age - a longitudinal study.
AB  - OBJECTIVES: To explore a possible relationship between the caries experience and
      pattern in the primary dentition at 5 years of age and the permanent dentition at
      10 years of age. Further, to examine the possibility of predicting children in a
      caries-risk group at 5 years verified at 10 years of age. MATERIALS AND METHODS:
      A sample of 186 children (90 males) were clinically examined as 5-year-olds and
      re-examined as 10-year-olds by calibrated dentists. A five-graded diagnostic
      system including enamel caries was used. Bitewing radiographs were taken. A true
      risk group of children at 10 years were defined as those with at least one dentin
      or filled lesion on the mesial surface of 6-year molars, and/or on incisors,
      and/or total DMFS (decayed, missing, and filled surfaces) more than 1 SD above
      the mean. The prediction was measured in terms of OR (odds ratio),
      sensitivity/specificity, and receiver operating characteristic curves. RESULTS:
      Statistically significant correlations (r=0.5) were found between the caries
      experience in the two dentitions as well as between the primary second molars at
      baseline and the permanent teeth at 10 years. 'Primary second molars' and 'all
      primary molars' were the most powerful predictors for allocation into the risk
      group (24% of the sample). The highest achieved sum of sensitivity and
      specificity, 148%, was attained at a cut-off point above two carious surfaces in
      enamel and/or dentin in primary second molars. CONCLUSIONS: Statistically
      significant relationship in disease between the dentitions was found. More than
      two surfaces with caries experience in primary second molars are suggested as a
      clinically useful predictor at 5 years of age for being at high risk at age 10.

PMID- 16643536
TI  - Clinical randomized controlled trial of chemomechanical caries removal
      (Carisolv).
AB  - OBJECTIVES: The purpose of this study was to compare the chemomechanical caries
      removal system (Carisolv) with high-speed excavation in cavitated occlusal caries
      of primary molars. Design and setting. The study was a randomized controlled,
      clinical trial in which the two techniques were compared in each subject.
      Participants were chosen from public schools, in Maracaibo County, Zulia State,
      Venezuela. SAMPLE AND METHODS: The sample consisted of 80 primary molars selected
      from 40 children (mean age 7.7+/-0.7 years). Each patient had at least two
      contralateral primary molars with cavitated occlusal caries and approximately
      equal-size access to lesions. The outcome variables were: clinically complete
      caries removal, size of the opening of the cavity, volume of carious tissue
      removed, pain during caries removal, anaesthesia requested by the patient, caries
      removal time, and behaviour and preference of patients. RESULTS: All treated
      molars were clinically caries free whichever caries-removal procedure was used.
      When Carisolv' was used the final cavity entrance sizes were smaller (P<0.001)
      and the estimated volume of tissue removed was less (P<0.001). The time taken for
      caries removal was three times longer (7.51+/-1.83 min, P<0.001). Some pain was
      reported by seven (17.5%) participants when Carisolv was used, compared with 16
      (40%) when high-speed excavation was used (P<0.05). Using the Carisolv method
      there was a higher proportion of patients with positive behaviour (P<0.01), and
      71.0% (P<0.05) preferred this treatment. CONCLUSION: Carisolv is an effective
      clinical alternative treatment for the removal of occlusal dentinal caries in
      cavitated primary molars; it is more conservative of dental tissue and appeared
      to be more comfortable for most patients, although the clinical time spent is
      longer than when using high-speed excavation.

PMID- 16643537
TI  - Pattern of fluid consumption in a sample of Saudi Arabian adolescents aged 12-13
      years.
AB  - OBJECTIVE: To study the pattern of fluid consumption in a group of Saudi
      adolescent boys and girls aged 12-13 years. DESIGN: Prospective study. METHODS:
      Three hundred forty-four boys and girls attending school in Riyadh recorded their
      fluid intake for three consecutive days, including one weekend day, in April and
      May 2002. Types of drink/beverage and total amount consumed were analysed and
      ranked in order of amount/quantity of consumption. Independent samples t-test was
      used to compare between genders. RESULTS: Mean daily fluid intake was 1,917 mL
      (SD 287). Drinking water provided 37%, whereas carbonated soft drinks and fruit
      juice/drink accounted for 26% and 25%, respectively. Seven percent of total fluid
      intake amounting to 134 mL came from milk and 5% (103 mL) was from tea/coffee.
      Fluid intake was higher in boys (2,006 mL) than in girls (1,821 mL) (P=0.049).
      This was also true for carbonated soft drinks (P=0.050) and tea/coffee (P=0.000).
      Girls consumed more milk (P=0.001) and fruit juice/drink (P=0.001) than boys.
      CONCLUSION: Both carbonated soft drink and fruit juice/drink accounted for the
      largest proportion of total fluid intake by the sampled Saudi adolescents to the
      detriment of nutritious milk.

PMID- 16643538
TI  - Erosive effect of an antihistamine-containing syrup on primary enamel and its
      reduction by fluoride dentifrice.
AB  - AIM: This study evaluated the action of an antihistamine-containing syrup
      (Claritin D) on enamel that was subsequently submitted or not to applications of
      fluoride dentifrice. METHODS; Two hundred sixty-four slices (n=44 per subgroup)
      prepared from exfoliated primary molars were evaluated in hardness tests. Six
      subgroups were submitted to different treatments for 10 days. The controls
      underwent pH cycling with (positive control) or without (negative control) three
      daily immersions in fluoride dentifrice/distilled water slurry. The test
      subgroups related to daytime use of the antihistamine syrup underwent pH cycling
      and two 5-min applications of Claritin D, coupled or not to the three daily
      immersions in the fluoride slurry. The subgroups related to nocturnal use of the
      syrup were submitted to the same procedures of daytime subgroups, respectively,
      but with one of the applications of Claritin D lasting for 8 h. RESULTS: The
      median hardness values obtained after use of the syrup were significantly lower
      than the initial ones. Equivalent values for subgroups submitted to fluoride
      applications in addition to treatment with the syrup were significantly higher.
      CONCLUSION: It was concluded that the antihistamine-containing syrup reduced the
      hardness of primary enamel and that, in this experiment, the use of fluoride
      dentifrice was able to diminish this erosive effect.

PMID- 16643539
TI  - Periodontal treatment need of the 6th-grade Jordanian pupils.
AB  - AIM: The purpose of this study was to assess the periodontal treatment needs of
      6th-grade Jordanian pupils aged 12 years old. METHODS: Forty-eight classes
      teaching 6th-grade pupils were randomly selected from the six education zones in
      Irbid region, Jordan. The data were collected during interviews and clinical
      examinations using the Community Periodontal Index of Treatment Needs (CPITN)
      criteria. RESULTS: The findings revealed that 27.5% of the examined pupils had
      healthy periodontium, 22.9% showed gingival bleeding on probing but no calculus,
      and 31.4% had calculus deposits. Pockets in the 4-5 mm range were found in 17.6%
      and those in the>6 mm range in 0.6% of the pupils. Healthy periodontium was found
      in 2.9 sextants, whereas 2.7 sextants showed gingival bleeding and calculus.
      Periodontal pockets were demonstrated in less than 0.4 sextants. Periodontal
      therapy was not required for 27.5% of the pupils. The rest of the pupils (72.5%),
      however, needed oral hygiene improvement, and of these 50% required professional
      calculus removal. CONCLUSION: This study indicated that about 73% of the sample
      needed oral hygiene instructions and motivation, 50% needed professional scaling,
      and 0.6% needed periodontal therapy. The data of this study establish a baseline
      data, which may help in planning dental services and initiating further research.

PMID- 16643540
TI  - Total antioxidant levels of saliva in children related to caries, age, and
      gender.
AB  - AIM: The purpose of this study was to evaluate the relationship between the
      physicochemical properties of saliva such as flow rate, buffering capacity, pH,
      calcium level, total protein, total antioxidant status, and dental caries, age,
      and gender. MATERIAL AND METHODS: The antioxidant activity of saliva was
      investigated in 80 healthy children aged 7-15 years. They were divided into
      subgroups according to gender, age (7-10 years and 11-15 years), and caries
      activity (caries active=CA and caries free=CF). Unstimulated saliva samples were
      collected from all groups. Flow rates were determined, and samples analysed for
      pH, buffer capacity, calcium, total proteins, and total antioxidant status.
      Salivary total antioxidant activity (TAA) was estimated by an adaptation of the
      ABTS (2,2-azino-di (3-ethylbenzthiazoline-6-sulphonate)) assay. RESULTS: The
      results indicated that in general, although there was no linear association
      between salivary flow rate pH and buffering capacity values obtained from
      different groups, salivary calcium concentration values were found to be higher
      in caries free groups. Total protein and total antioxidant values were higher in
      caries active groups except those in the 11- to 15-year-old girls group.
      CONCLUSION: In general, total protein and total antioxidant insaliva were
      increased with caries activity. Calcium concentrations in saliva were higher in
      caries-free children. In addition, calcium concentration increased with age.
      Thus, it can be concluded that a linear association exists between calcium
      concentration age and caries activity. More clinical and laboratory studies are
      needed to determine the exact relationship between the physicochemical properties
      of saliva such as flow rate, buffering capacity, pH, calcium level, total
      protein, total antioxidant status, and dental caries, age, and gender.

PMID- 16643541
TI  - The effect of different milk formulas on dental plaque pH.
AB  - OBJECTIVES: The purposes of this study were (1) to investigate the effect of
      different milk formulas on dental plaque pH after rinsing with these three
      categories, type of protein-based formulas (milk-based, soy-based, protein
      hydrolysate), type of sugar (only lactose, lactose and other sugars, only non
      milk extrinsic sugars), and casein ratio (high and low casein), and (2) to
      observe organic acids formed by different milk formulas. METHODS: Baseline plaque
      pH and plaque pH at 2, 5, 10, 15, 20, 25, 30, and 60 min after rinsing with milk
      formulas were recorded by a combination electrode in 14 healthy subjects.
      Deionized water and 10% sucrose were used as a negative and positive control. The
      plaque sample was also analysed to identify and quantify the organic acids using
      a high-performance liquid chromatography. Parameters including minimum pH,
      maximum pH drop, and area under curve were compared by RMANOVA and paired t-test.
      RESULTS: The minimum pH was not significantly different among different protein
      based formulas, whereas, the maximum plaque pH drop of soy-based and milk-based
      formula was significantly higher than that produced by protein hydrolysate
      formula (P=0.022 and 0.03, respectively). Area under curve produced by soy-based
      and milk-based formulas was significantly larger than that created by protein
      hydrolysate formula (P=0.025 and<0.001, respectively). Milk formulas containing
      only lactose caused significantly less plaque pH change in minimum pH (P<0.001),
      maximum pH drop (P=0.003), and area under curve (P<0.001) when compared with
      formulas containing lactose and other sugar but not with special formulas
      containing only non-milk extrinsic sugar. Similarly, special formulas containing
      non-milk extrinsic sugar produced significantly lower minimum pH and smaller area
      under curve than formulas containing lactose and other sugar did (P=0.044 and
      0.009, respectively). No different results were found between high and low casein
      follow-on formulas. Lactic acid was produced more by rinsing with formulas
      containing lactose and other sugars than that produced by formulas containing
      only lactose. CONCLUSIONS: This study suggests that milk formulas containing
      added other sugars tend to cause a decrease in plaque pH.

PMID- 16643542
TI  - Is there life after Buckley's formocresol? Part II - Development of a protocol
      for the management of extensive caries in the primary molar.
AB  - OBJECTIVE: To produce a working clinical protocol for pulp therapy techniques in
      the extensively carious primary molar. INTRODUCTION: The International Agency for
      Research on Cancer has recently classified formaldehyde as carcinogenic to human
      beings. As such, a medicament that can be used to replace formocresol in clinical
      practice should be identified. METHODS: Part I of this paper explored the
      currently available alternative interventions and materials to formocresol in the
      form of a narrative review following an extensive literature search. Part II now
      presents the formation of a specialist group to establish an evidence-based
      protocol, for the management of the extensively carious primary molar.
      CONCLUSION: A protocol and key points document have been developed to assist
      clinicians in their treatment planning. Areas for further postgraduate training
      are identified.

PMID- 16643543
TI  - Hurler's syndrome: dental findings in a case treated with bone marrow
      transplantation in infancy.
AB  - Hurler's syndrome, also known as mucopolysaccharidosis I (MPS I-H), is a rare
      condition inherited as an autosomal recessive trait. It is caused by a deficiency
      in alpha-L-iduronidase, an enzyme that participates in the degradation of the
      glycosaminoglycans (GAGs) heparin sulphate and dermatan sulphate. Children with
      Hurler's syndrome appear nearly normal at birth but, left untreated, show a
      progressive mental and physical deterioration caused by a build-up of GAGs in all
      organs of the body. Death is often caused by cardiac or respiratory failure and
      usually occurs before the second decade of life. In recent years, bone marrow
      transplantation (BMT) has been employed in the management of patients with
      Hurler's syndrome. However, the dental findings observed in these cases have not
      previously been reported in the dental literature. Here we report a patient aged
      11 years and 6 months, presented to a Specialist Paediatric Dentistry Unit, who
      was successfully treated by BMT at 18 months of age.

PMID- 16643544
TI  - A case of Coffin-Lowry syndrome with premature exfoliation of primary teeth.
AB  - We present a case of a 5-year-old boy with premature exfoliation of primary
      teeth. All eight primary incisors had exfoliated by the age of 3 years, and three
      canines and one primary first molar were subsequently lost when he was 4 years
      old. None of the exfoliated teeth exhibited caries. The boy also showed
      characteristic facial changes, tapering of the fingers, and mental and motor
      retardation. Based on these findings, he was diagnosed as having Coffin-Lowry
      syndrome. Premature exfoliation of primary teeth in Coffin-Lowry syndrome has
      been described in a few reports. This manifestation of the disease would be
      helpful for diagnosis at an early stage as those previous reports suggested.

PMID- 16643545
TI  - Apert syndrome with glucose-6-phosphate dehydrogenase deficiency: a case report.
AB  - Apert syndrome is characterized by midface hypoplasia, syndactyly of the hands
      and feet, proptosis of eyes, steep and flat frontal bones, and premature union of
      cranial sutures. Maxillary hypoplasia, deep palatal vault, anterior open bite,
      crowding of the dental arch, severely delayed tooth eruption, and dental
      malocclusion are the main oral manifestations of this syndrome. In this report, a
      case of Apert syndrome with glucose-6-phosphate dehydrogenase (G(6)PD) deficiency
      is presented. The patient, a 4-year-old male and the fourth child of healthy
      parents, was admitted to our department because of delayed tooth eruption. He had
      all the cardinal symptoms of the Apert syndrome. Clinical examination revealed
      that primary centrals, canines and first molars erupted; however, primary second
      molars and laterals had not erupted. The patient had no dental caries. Preventive
      treatments were applied, and subsequently, the patient was taken to long-term
      follow up.

PMID- 16643546
TI  - Kabuki syndrome: oral and general features seen in a 2-year-old Chinese boy.
AB  - This report describes the case of a young Chinese boy with Kabuki syndrome (KS).
      KS is a congenital condition characterized by multiple anomalies, especially of
      the face, and is usually associated with mild to moderate mental retardation. The
      patient presented with the characteristic facial features of KS and some skeletal
      and neurological anomalies including a butterfly vertebrae with scoliosis,
      cerebral atrophy, and irregular dentition. Dental examination revealed
      screwdriver-shaped incisors and a high arched maxilla, features typical of
      patients with KS, as well as very poor oral hygiene and early childhood caries.
      This report includes discussion of the aetiology of KS as well as discussion of
      the long-term prognosis for this particular patient, and patients with KS in
      general, with consideration of associated dental and medical issues.

PMID- 16643547
TI  - Mandibular first and second molar tooth transposition: a case report.
AB  - A case is reported of what appears to be a transposition affecting the mandibular
      first, second, and third molars. The possible aetiology is discussed in relation
      to previously published studies. In the case described the primary actilogical
      factor appears to intraosseous migration of the developing tooth germ.

PMID- 16643548
TI  - Reliability, validity, and clinical utility of the Migraine-ACT questionnaire.
AB  - BACKGROUND: The 4-item Migraine-ACT questionnaire is an assessment tool for use
      by primary care physicians to identify patients who require a change in their
      current acute migraine treatment. It has been shown to be easy to use, and to be
      reliable and accurate in its assessments. OBJECTIVES: To further analyze the
      Migraine-ACT study database, providing additional information on the reliability,
      validity, and potential clinical utility of the questionnaire. METHODS:
      Reliability was assessed by recording the distribution of Migraine-ACT scores
      recorded at baseline and 1 week later (test-retest reliability). Analyses of
      consistency of Migraine-ACT scores were conducted on the total sample of patients
      and for the separate centers, using Pearson and Spearman correlations. Validity
      was assessed by comparing the t-discrimination values for clinically relevant
      questions within domains of the original 27-item questionnaire. Reliability and
      validity were also assessed by constructing an "alternative" (Form B) Migraine
      ACT questionnaire, derived from an analysis of the second-best items in each
      domain in the original study data. Clinical utility was assessed using Pearson
      pairwise correlations to compare Migraine-ACT scores with clinically defined
      criteria as analyzed by the SF-36 Quality of Life questionnaire, the Migraine
      Disability Assessment (MIDAS) questionnaire, and the Migraine Therapy Assessment
      (MTAQ) questionnaire. RESULTS: The distribution of Migraine-ACT scores between
      the 2 completions of the questionnaire was consistent for the total sample (test
      retest reliability, r= .81) and between the individual countries (r= .61 to .92).
      In this study, the validity (assessed as t-discrimination) of the Migraine-ACT
      "impact" and "global assessment of relief" questions were markedly higher than
      those of other endpoints used in migraine clinical studies. The Form B Migraine
      ACT questionnaire was almost as reliable and accurate as the original Form A
      questionnaire. The distribution of Migraine-ACT scores was: 0 = 12.6%, 1 = 13.7%,
      2 = 14.7%, 3 = 20.5%, and 4 = 38.4%. The change in Migraine-ACT score correlated
      with, and had a linear relationship with changes in SF-36, MIDAS, and MTAQ
      scores, and indicated that a Migraine-ACT score of <or=2 corresponded with a need
      to consider changing the patient's acute medication. About 40% of the migraine
      patients in the study scored <or=2 and may have had significant unmet treatment
      needs. CONCLUSIONS: These data confirm the excellent reliability and validity of
      the Migraine-ACT questionnaire and provide further evidence for its utility in
      clinical practice.

PMID- 16643549
TI  - Workplace absenteeism and aspects of access to health care for individuals with
      migraine headache.
AB  - OBJECTIVES: (1) To examine the relationship between access to care and the number
      of missed workdays, and (2) to determine how this relationship is confounded by
      the presence of having health insurance and health care use among migraineurs.
      DESIGN/METHODS: This retrospective, pooled, cross-sectional study used 1996 to
      1999 Medical Expenditure Panel Survey data. Employed migraineurs who were between
      18 and 65 years of age were included. Individuals reporting a neoplastic or an
      acute pain condition were excluded. An access to care index was developed using
      Rasch Partial Credit Analysis. A 2-part model was used to estimate the annual
      number of missed workdays. RESULTS: Of the 703 migraineurs, 538 (77%) reported
      missing work time. Of those who missed work, the mean (SE) annual number of
      missed workdays was 4.4 (.39). A higher level of access to care (P= .025) and
      presence of depression (P= .033) were significantly associated with missing a
      greater number of workdays. We created a proxy for migraine severity based on
      migraine-related prophylactic medication use and hospitalization(s). Severe
      migraines were significantly (OR = 2.01, SE = .51, P= .006) associated with an
      increased likelihood to miss workdays. When health insurance was included in the
      model, a higher level of access to care was significantly associated with the
      increased likelihood to miss workdays (OR = 1.04, SE = .021, P= .05). From the
      original model, the odds ratio (1.035 to 1.040) and the SE (.020 to .021)
      increased slightly. When health care use was included in the model and health
      insurance was removed, (1) emergency department visits were significantly (P=
      .006) associated with missing a greater number of workdays, and (2) access to
      care was significantly associated with missing a greater number of workdays (P=
      .028). When having health insurance and health care use were simultaneously
      included in the model, a higher level of access to care was significantly
      associated with greater likelihood to miss work (OR = 1.040, SE = .0212, P= .05)
      and missing a greater number of workdays (P= .005). However, a change of 1
      standard deviation in the score would be associated with a 12% change in the odds
      to miss work and only 8 percentage points change in the number of missed
      workdays. CONCLUSIONS: Contrary to expectations, a higher level of access to care
      is significantly associated with an increased likelihood to miss work and with
      missing a greater number of workdays. Depression, migraine severity, and health
      care use are important explanatory variables. Having health insurance may be a
      confounder between access to care and workplace absenteeism.

PMID- 16643550
TI  - Subcutaneous sumatriptan for refractory trigeminal neuralgia.
AB  - BACKGROUND: Mechanical compression of the trigeminal root by an artery is thought
      to cause trigeminal neuralgia. The 5-HT(1B/1D) receptor agonist may inhibit
      neurogenic inflammation and vasodilation near the irritated trigeminal root.
      OBJECTIVE: To examine the effectiveness of a 5-HT(1B/1D) receptor agonist,
      sumatriptan, on a paroxysmal pain in trigeminal neuralgia. METHODS: Twenty-four
      patients with trigeminal neuralgia refractory to previous treatment were
      randomized to receive subcutaneously either 3 mg (1 mL) of sumatriptan or 1 mL of
      saline placebo. Following a 7-day period, patients crossed over to receive the
      alternative treatment. Paroxysmal pain triggered by touching or moving the face
      was assessed with VAS before and 15 minutes after the treatment. Patients used a
      descriptive scale to pain-grade outcome, and asked to note whether the pain
      returned and how long after therapy it recurred. RESULTS: Subcutaneous
      sumatriptan, but not placebo, significantly decreased VAS from 8.3 +/- 2.1 to 2.4
      +/- 3.0 cm (mean +/- SD). The number of patients who described their pain as
      moderately or slightly better was 20 in the sumatriptan group and 1 in the
      placebo group. The effect of subcutaneous sumatriptan persisted for a median
      period of 7.9 hours (range: 1-20 hours). CONCLUSIONS: Subcutaneous sumatriptan
      produced prompt analgesia without serious adverse reactions in patients with
      trigeminal neuralgia refractory to previous treatment.

PMID- 16643552
TI  - Platelet levels of dopamine are increased in migraine and cluster headache.
AB  - OBJECTIVE: To measure plasma and platelet levels of dopamine in patients with
      migraine with aura, migraine without aura, and cluster headache. BACKGROUND:
      Clinical, genetic, and pharmacological evidences suggest that an abnormality of
      dopaminergic system plays a role in migraine pathogenesis. Direct evidence of an
      abnormal metabolism of dopamine in migraine, however, is lacking. METHODS: Plasma
      and platelet levels of dopamine were measured in patients with migraine with aura
      or migraine without aura during headache-free periods and in patients with
      cluster headache during the remission and active periods, as compared with
      healthy control subjects, using a multichannel electrochemical high-performance
      liquid chromatography system. RESULTS: Plasma levels of dopamine were not
      detectable with our methodology. Platelet levels of dopamine were higher in both
      types of migraine (migraine without aura = .20 +/- .17 ng/10(8) platelets;
      migraine with aura = .16 +/- .19 ng/10(8) platelets) than in control subjects
      (.10 +/- .11 ng/10(8) platelets), although in migraine with aura patients the
      difference was not significant. Patients with cluster headache showed the highest
      levels of platelet dopamine (.34 +/- .36 ng/10(8) platelets). CONCLUSIONS: Our
      results support the hypothesis that the dopaminergic system is impaired in
      migraine and cluster headache and suggest that high platelet levels of dopamine
      may represent an abnormal biochemical phenotypic trait of these primary
      headaches.

PMID- 16643553
TI  - Plasma 5-hydroxytryptamine (5-HT) in migraine during an attack-free period.
AB  - OBJECTIVE: We measured the plasma 5-HT, 5-hydroxytryptophan (5-HTP), and
      tryptophan levels in controls, migraine patients with aura (MWA), and migraine
      patients without aura (MWoA) during an attack-free period. BACKGROUND: Serotonin
      (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of
      migraine. The precise relationship between 5-HT and migraine, however, remains
      unclear. METHODS: Blood samples in controls, MWA, and MWoA patients during an
      attack-free period were collected from brachial arteries and analyzed using HPLC.
      RESULTS: The plasma tryptophan and 5-HTP levels were not significantly different
      between the controls and migraine patients (either MWA or MWoA). However, the
      plasma 5-HT level in the MWA patients was significantly lower than that in the
      controls and MWoA patients. CONCLUSIONS: The present data suggest that reduced
      levels of 5-HT in MWA may result from either a dysfunction in the enzymes
      involved in serotonin biosynthesis or a dysfunction in 5-HT release or uptake
      from platelets and lymphocytes. These findings indicate the existence of a
      serotonin metabolism dysfunction in MWA patients that may differ from the state
      of serotonin metabolism in MWoA patients.

PMID- 16643554
TI  - Endocrine function is altered in chronic migraine patients with medication
      overuse.
AB  - OBJECTIVE: To evaluate the effects of analgesic overuse on endocrine function in
      patients with chronic migraine and medication-overuse headache (CM-MOH).
      BACKGROUND: Chronic migraine is frequently associated with an overuse of
      symptomatic medications. Drugs currently used in acute migraine attacks are
      associated with several endocrine effects. At present, the endocrine effects of
      medication overuse in chronic migraine patients are unknown. METHODS: Eighteen
      patients with CM-MOH, diagnosed according to the ICHD-II criteria, and 18 healthy
      controls received an intravenous administration of GHRH, hCRH, and TRH. Plasma
      concentrations of GH, TSH, ACTH, and cortisol were measured for a 90-minute
      period after administration of the specific releasing hormones. RESULTS: Hormonal
      basal concentrations were similar in both groups. GH response to GHRH was
      significantly reduced in patients with CM-MOH in comparison with controls. TRH
      induced a reduction of TSH concentrations only at the end of the test. After hCRH
      administration, ACTH and cortisol concentrations were significantly higher in
      cases than in controls. A significant correlation between duration of the disease
      and altered hormonal response was found. CONCLUSIONS: Our study shows that both
      corticotropic and somatotropic functions are significantly impaired in CM-MOH
      patients and suggests a role for hormones in the development of chronic migraine.

PMID- 16643555
TI  - The prevalence and spectrum of sleep problems in women with transformed migraine.
AB  - OBJECTIVES: It is our clinical observation that patients with transformed
      migraine (TM) almost invariably report nonrestorative sleep. In this study we
      sought first to validate that clinical observation, then to describe the
      prevalence and spectrum of factors that might contribute to nonrestorative sleep
      in a TM population. BACKGROUND: Although headaches have been linked with sleep
      problems for over a century, there is little information about the spectrum or
      prevalence of specific sleep problems associated with TM in adults. METHODS: We
      conducted a detailed sleep interview on 147 consecutive women with TM. Subjective
      sleep quality was assessed by asking patients to describe their state upon
      awakening as "refreshed" or "tired." RESULTS: None of the 147 patients reported
      awakening "refreshed," and 83.7% stated that they awakened "tired." Sleep
      complaints were prevalent and varied in this population. CONCLUSIONS: Although
      the relationship between pain and sleep is complex and ill understood, we found a
      very high prevalence of nonrestorative sleep and a similarly high prevalence of
      modifiable poor sleep habits in patients with TM. Since behavioral approaches
      have been found effective in improving sleep quality in patients with poor sleep
      hygiene, we propose that studies be undertaken to assess the impact of such
      treatment on TM.

PMID- 16643556
TI  - Color vision but not visual attention is altered in migraine.
AB  - OBJECTIVE: To examine visual search performance in migraine and headache-free
      control groups and to determine whether reports of selective color vision
      deficits in migraine occur preattentively. BACKGROUND: Visual search is a classic
      technique to measure certain components of visual attention. The technique can be
      manipulated to measure both preattentive (automatic) and attentive processes.
      Here, visual search for colored targets was employed to extend earlier reports
      that the detection or discrimination of colors selective for the short-wavelength
      sensitive cone photoreceptors in the retina (S or "blue" cones) is impaired in
      migraine. METHOD: Visual search performance for small and large color differences
      was measured in 34 migraine and 34 control participants. Small and large color
      differences were included to assess attentive and preattentive processing,
      respectively. In separate conditions, colored stimuli were chosen that would be
      detected selectively by either the S-, or by the long- (L or "red") and middle (M
      or "green")-wavelength sensitive cone photoreceptors. RESULTS: The results showed
      no preattentive differences between the migraine and control groups. For active,
      or attentive, search, differences between the migraine and control groups
      occurred for colors detected by the S-cones only, there were no differences for
      colors detected by the L- and M-cones. The migraine group responded significantly
      more slowly than the control group for the S-cone colors. CONCLUSIONS: The
      pattern of results indicates that there are no overall differences in search
      performance between migraine and control groups. The differences found for the S
      cone colors are attributed to impaired discrimination of these colors in migraine
      and not to differences in attention.

PMID- 16643557
TI  - Use of complementary and alternative medicine by patients with chronic tension
      type headache: results of a headache clinic survey.
AB  - OBJECTIVES: This study was undertaken to evaluate the rates, pattern, and
      presence of predictors of complementary and alternative medicine use in a
      clinical population of patients with chronic tension-type headache. BACKGROUND:
      The use of complementary and alternative medicine in the treatment of headaches
      is a growing phenomenon about which little is known. METHODS: A total of 110
      chronic tension-type headache patients attending a headache clinic participated
      in a physician-administered structured interview designed to gather information
      on complementary and alternative medicine use. RESULTS: Past use of complementary
      and alternative therapies was reported by 40% of the patients surveyed (22.7% in
      the previous year). Chronic tension-type headache patients prefer complementary
      and alternative practitioner-administered physical treatments to self-treatments,
      the most frequently used being chiropractic (21.9%), acupuncture (17.8%), and
      massage (17.8%). Only 41.1% of the patients perceived complementary and
      alternative therapies to be beneficial. The most common source of recommendation
      of complementary and alternative medicine was a friend or relative (41.1%). Most
      of the chronic tension-type headache patients used complementary and alternative
      treatment as a specific intervention for their headache (77.3%). Almost 60% of
      complementary and alternative medicine users had not informed their medical
      doctors of their use of complementary and alternative medicine. The most common
      reasons given for choosing to use a complementary or alternative therapy was the
      "potential improvement of headache" it offered (45.4%). The patients who had used
      more complementary and alternative treatments were found to be those recording a
      higher lifetime number of visits to conventional medical doctors, those with a
      comorbid psychiatric disorder, those enjoying a higher (household) income, and
      those who had never tried a preventive pharmacological treatment. CONCLUSIONS:
      Our findings suggest that headache-clinic chronic tension-type headache patients,
      in their need of and quest for care, seek and explore both conventional and
      complementary and alternative therapies, even if only 41.1% of them perceived
      complementary treatments as effective. Physicians should be made aware of this
      patient-driven change in the medical climate in order to prevent misuse of health
      care resources and to be better equipped to meet patients' care requirements.

PMID- 16643558
TI  - Acupuncture for chronic headaches--an epidemiological study.
AB  - OBJECTIVE: To investigate the characteristics and outcomes of patients undergoing
      acupuncture treatment for chronic headaches under conditions of routine care
      provided within the framework of statutory health insurance in Germany.
      Furthermore, we investigated correlations between different outcomes. PATIENTS
      AND METHODS: Patients with migraine, episodic or chronic tension-type headache
      (TTH), or several other forms of chronic headache (cluster, vascular, drug
      induced headache; other specific headaches) treated with acupuncture (mean number
      of sessions 8.6 +/- 3.0) were included into an observational study. Detailed
      questionnaires including questions on headache days and instruments measuring
      disability (Pain Disability Index) and quality of life (SF-36) were completed
      before treatment, after treatment, and at 6 months after inclusion. RESULTS: A
      total of 2,022 patients (732 with migraine, 351 with episodic and 440 with
      chronic TTHs, and 499 with other diagnoses) treated by 1,418 physicians were
      included in the main analysis. Sociodemographic and baseline characteristics
      differed considerably in the four diagnostic groups. Statistically highly
      significant and clinically relevant improvements were seen for all clinical
      outcome measures in all diagnostic groups. In 52.6% of patients headache
      frequency decreased by at least 50% compared to baseline. The comparison of
      headache frequency, pain intensity, and generic outcome measures showed that some
      of these outcomes correlate only weakly. CONCLUSIONS: In this epidemiological
      study, headache patients reported clinically relevant improvements after
      receiving acupuncture. Randomized trials performed in parallel to this study
      confirm the relevant overall effect, however, the effect may largely be due to
      potent unspecific needling and placebo effects.

PMID- 16643559
TI  - Comparison of the effect of topiramate and sodium valporate in migraine
      prevention: a randomized blinded crossover study.
AB  - BACKGROUND: Topiramate and sodium valporate are anticonvulsants, demonstrated to
      be effective as monotherapy for migraine prevention in placebo-controlled trials.
      OBJECTIVES: To compare the relative efficacy of topiramate and sodium valporate
      in the prevention of migraine. PATIENTS AND METHODS: A 24-week, randomized,
      double-blind, crossover, clinical trial was conducted from October 2003 to
      September 2004. A total of 64 patients with migraine headache, aged 14 to 57
      years, were randomly allocated to the 2 treatment groups. The first group
      received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2
      months. The second group received sodium valporate (200 mg daily increment over 1
      week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16,
      and 24 weeks after start of therapy. RESULTS: Topiramate appeared to be
      equivalent in efficacy and safety to sodium valporate. A significant decrease in
      duration, monthly frequency, and intensity of headache occurred in both groups.
      Of the 32 patients treated with sodium valporate, the mean standard deviation
      (SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode
      per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale
      (VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001).
      Correspondingly, in the 32 patients treated with topiramate, the mean SD of
      monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month,
      headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3
      (8.4) to 3.9 (2.7) hours (P < .001). CONCLUSION: This study demonstrates that
      treatment with topiramate and sodium valporate both significantly reduce migraine
      headache. This effect of topiramate and sodium valporate has previously been
      shown to reduce migraine headache, and we postulate that treatment with
      topiramate and sodium valporate may have a similar benefit.

PMID- 16643560
TI  - Headache prevalence in adolescents aged 12 to 17: a student-based epidemiological
      study in Bursa.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the
      prevalence and sociodemographic characteristics of headaches among Turkish
      adolescents aged 12 to 17 years old in Bursa province of Turkey. METHODS: A
      multistep, stratified, cluster sampling method was used for subject selection.
      The estimated sample size for 12- to 14-year-old students was 1,270 and for 15-
      to 17-year-old students was 1,117. Our study sample included 6.5% of the
      secondary schools and 1.8% of the students aged 12 to 17 years old. The study was
      conducted in two phases; the questionnaire phase and the face-to-face interview
      phase. RESULTS: The prevalence of recurrent headache in the study population was
      52.2%. Girls (59.8%) had significantly more recurrent headache than boys (45.1%)
      The prevalence of recurrent headache increased from 42.2% up to 60.7% by age. In
      multivariate logistic regression analysis age and gender differed significantly
      between adolescents with and without recurrent headache groups. Frequent episodic
      tension-type headache was the most common (25.9%) headache among Turkish
      adolescents, followed by migraine (14.5%). CONCLUSIONS: Age and gender appeared
      to be demographic factors increasing adolescent headache prevalence. Frequent
      episodic-tension type headache was the most common headache followed by migraine.
      Our migraine prevalence was slightly higher than most of the previously reported
      prevalence rates. This might be due to the new classification criteria of
      headache released by International Headache Society.

PMID- 16643561
TI  - Age-dependent relationships among pain, depressive symptoms, and functional
      disability in youth with recurrent headaches.
AB  - OBJECTIVE: To assess age differences associated with depressive symptoms and
      functional disability in children and adolescents with recurrent headache.
      BACKGROUND: Research has indicated that psychological factors, especially
      depression, are related to the extent and nature of functional disability
      experienced from headaches. There is a lack of research examining how age impacts
      the relationship between pain, psychological factors, and activity restriction in
      children and adolescents with recurrent headache. METHODS: Seventy-seven
      participants from a pediatric neurology clinic completed self-report measures of
      pain intensity, depressive symptoms, and functional disability. RESULTS: Findings
      demonstrated a significant positive correlation between pain and functional
      disability, and depressive symptoms and functional disability for children.
      Correlations for adolescents failed to reach significance. Functional disability
      emerged as a mediator between headache pain and depressive symptoms for children
      but not for adolescents. CONCLUSIONS: Results indicate potentially important age
      differences when examining the impact of functional disability on depressive
      symptoms in this sample. Findings suggest that functional disability may
      contribute to depressive symptoms differently for children versus adolescents
      with recurrent headache. Age-specific interventions that differentially focus on
      the specific roles that pain, depressive symptoms, and disability have for
      children and adolescents with recurrent headache may be warranted.

PMID- 16643562
TI  - Patent foramen ovale and migraine--bringing closure to the subject.
AB  - There is increasing interest in the relationship between migraine and patent
      foramen ovale (PFO). PFO is more common in migraineurs with aura, and migraine
      with aura is more prevalent in patients with PFO. Retrospective analyses of PFO
      closure for stroke prevention and decompression illness in divers have suggested
      that migraineurs with and without aura may derive significant benefit from PFO
      closure, but to date no prospective, randomized, sham-controlled study to confirm
      this has been completed. Herein we review published data regarding the
      relationship between migraine and PFO and discuss the rationale, justification,
      and important factors to consider in the conduct of prospective, controlled,
      clinical trials designed to evaluate the efficacy and safety of percutaneous
      device closure of PFO for migraine prevention.

PMID- 16643563
TI  - Could statins be useful in the treatment of patients with migraine?
AB  - Migraine is a common and disabling neurological disorder. Studies have shown that
      patients with migraine (especially those with typical aura with migraine) have an
      unfavorable cardiovascular risk profile and an increased risk of early-onset (<45
      years) ischemic stroke. Statins are effective hypolipidemic drugs that reduce
      cardiovascular-related morbidity and death in patients with or without
      established atherosclerotic vascular disease. We report a patient whose frequent
      attacks of typical aura with migraine completely resolved after the initiation of
      treatment with a statin. In this context, we comment on the possible effects of
      statins on the pathophysiology of migraine. We suggest that statins may be useful
      drugs in the treatment of migraine because they could reduce the increased
      cardiovascular risk in these patients and also attenuate migraine attacks. Only a
      randomized prospective study in this population could provide a definite answer
      to these speculations.

PMID- 16643564
TI  - Carotidynia in a 57-year-old man.

PMID- 16643565
TI  - The headaches that awaken us.

PMID- 16643566
TI  - Exploding head syndrome followed by sleep paralysis: a rare migraine aura.
AB  - A 26-year-old patient is described with a unique migraine aura. She described an
      8-year history of episodes occurring 1 to 2 times yearly of exploding head
      syndrome followed by sleep paralysis followed by a migraine headache. She also
      had identical headaches without aura about once per week. Both aura symptoms,
      which may occur in the brainstem, resulted in activation of the trigeminovascular
      system through an unknown mechanism.

PMID- 16643567
TI  - Side-locked headache as the chief complaint of inflammatory orbital pseudotumor
      (myositic form): a case report.
AB  - The case of a 38-year-old woman with continuous unilateral side-locked headache
      is reported. She had continuous right-sided periorbital pain of mild to moderate
      intensity for the past 5 months. She also reported a few episodes of pain
      exacerbations every day. She had no autonomic features. Based on a normal CT scan
      ordered by her general physician, we started indomethacin (150 mg/day) as well as
      celecoxib (400 mg/day) for 2 weeks, without relief. Oral prednisone for 6 days
      provided important relief, and she stayed on daily use of steroids, refusing
      other forms of therapy. After 5 months she developed orbital and eyelid edema,
      with painful restrictions to eye movement. Orbital MRI and pathological exam
      demonstrated inflammatory orbital pseudotumor (myositic form).

PMID- 16643568
TI  - Chronic paroxysmal hemicrania presenting as recurrent orbital inflammation.
AB  - Patients with chronic headache associated with ocular symptoms regularly seek
      ophthalmologists' opinions. We report an unusual case of chronic paroxysmal
      hemicrania (CPH), a rare but well-described variant of cluster headache in a
      female presenting to an eye department with recurrent episodes of severe
      unilateral periorbital swelling with a chronic history of headaches. Clinical
      features, review of literature, and therapeutic response to indomethacin helped
      to establish the diagnosis as CPH. This is the first report of severe orbital
      inflammation with CPH to our knowledge.

PMID- 16643569
TI  - Frequency and features of delayed alcohol-induced headache among university
      students.
AB  - The aim of this study was to describe the frequency and features of delayed
      alcohol-induced headache (DAIH) among university students. Ninety-five students
      were administered a headache questionnaire approximately 12 hours after have
      being exposed to high alcohol intake. Headache was mostly diffuse (44.4%),
      bilateral (92.5%), and throbbing (48.1%). This headache was usually severe and
      with important morbidity. Previous migraine has significantly increased the risk
      of DAIH.

PMID- 16643570
TI  - Transdermal Lidoderm for acute headache?

PMID- 16643571
TI  - Intranasal sumatriptan for prevention of post-ECT headaches.

PMID- 16643573
TI  - Recognition and therapeutic management of migraine in 2004, in France: results of
      FRAMIG 3, a French nationwide population-based survey.
AB  - OBJECTIVE: To evaluate the proportion of migraineurs who are self-aware of their
      disease in France, to determine the factors (disability, quality of life,
      psychiatric comorbidities, and medical consultation) that may promote self
      awareness of migraine, and to assess the influence of these factors on migraine
      attacks. BACKGROUND: New recommendations for migraine diagnosis and medical
      management were released in 2003 by the French medicoeconomic evaluation service
      (ANAES). In addition, the revised classification of headache disorders recently
      issued by the International Headache Society includes probable migraine as a form
      of migraine. However, strict and probable migraine now appear to be part of the
      same spectrum of disease. METHODS: Subjects with migraine (strict or probable)
      according to the revised classification were identified by a postal questionnaire
      from a large representative sample of the French adult population. Migraine
      related disability was assessed using the MIDAS questionnaire, anxiety and
      depression by the Hospital Anxiety and Depression scale (HADS), and health
      related quality of life (HRQoL) by the 8 concepts of the Short-Form 12 (SF-12)
      questionnaire. Migraine management was assessed according to the use of
      recommended or nonrecommended treatments, and treatment efficacy according to the
      set of 4 questions designed by the ANAES. RESULTS: Of the 10,532 subjects
      interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent
      of all migraine subjects were not self-aware that they had migraine. Medical
      consultation, duration of migraine history, severe intensity of attacks, impact
      on daily living, and female gender promoted self-awareness of migraine. On the
      other hand, HRQoL and anxiety and depression scores were not different between
      subjects self-aware or not self-aware of migraine. Only 20% of all migraine
      subjects were medically followed-up. Quality of the first medical consultation
      appears determinant for continued consulting. Subjects self-aware of migraine
      more frequently used recommended acute treatments of migraine, which proved more
      effective than nonrecommended treatments as assessed according to the ANAES set
      of questions. CONCLUSIONS: Migraine medical diagnosis and follow-up remain low in
      France. Careful medical consultation is a prime factor for migraine subject self
      awareness of migraine, continued consultation, and use of recommended medications
      for the treatment of migraine attacks.

PMID- 16643574
TI  - The impact of intensive patient education on clinical outcome in a clinic-based
      migraine population.
AB  - OBJECTIVE: To determine whether the addition of patient education to routine
      medical management improves the clinical status of migraine patients and reduces
      their utilization of healthcare resources. BACKGROUND: Optimal migraine
      management typically requires effective patient education. Such education often
      is difficult to accomplish in the busy clinic setting. METHODS: One hundred
      consecutive patients with migraine presenting to an university-based headache
      clinic were randomized to receive or not receive a standardized course of
      didactic instruction regarding migraine biogenesis and management. The course
      consisted of 3 classes taught by lay migraineurs who themselves previously had
      undergone intensive training. All patients were evaluated initially and at 1, 3,
      and 6 months by a neurologist blinded as to the results of randomization.
      Clinical variables examined included headache frequency/severity, migraine
      disability assessment (MIDAS) scores, patient compliance, presence versus absence
      of analgesic use/overuse, and headache-related unscheduled visits or phone calls.
      Comparisons were made between baseline findings and findings at the 6-month
      follow-up visit, with the change in mean MIDAS score serving as the primary
      outcome variable. RESULTS: At 6 months the group randomized to receive intensive
      education exhibited a significantly greater reduction in mean MIDAS score than
      the group randomized to routine medical management only (24 vs. 14 points; P <
      .05). Those patients also experienced a reduction in mean headache days per month
      and a greater reduction in functionally incapacitating headache days per month,
      exhibited less analgesic overuse and need for abortive therapy, were more
      compliant with prophylactic therapy prescribed, and made fewer headache-related
      calls to the clinic or unscheduled visits. CONCLUSION: Intensive education of
      migraine patients by trained lay instructors may convey significant benefit to
      those patients and reduce their utilization of healthcare resources.

PMID- 16643575
TI  - Changing physician knowledge, attitudes, and beliefs about migraine: evaluation
      of a new educational intervention.
AB  - OBJECTIVE: Use a presurvey of primary care providers (PCPs) enrolled in a
      continuing medical education (CME) program on headache management to ascertain
      their existing knowledge, attitudes, and beliefs regarding migraine and use a
      postsurvey to determine the extent to which the CME program has brought
      participant knowledge, attitudes, and skills closer to conformance with best
      evidence. BACKGROUND: Migraine is a common and debilitating condition, which PCPs
      may not always manage satisfactorily. In an effort to improve management, the
      American Headache Society has developed a CME program called BRAINSTORM that
      encourages PCPs to adopt the US Headache Consortium Guidelines for headache care.
      METHODS: A 20-item questionnaire was developed that covered the essential
      elements of migraine care. The questionnaire was administered before and after a
      BRAINSTORM presentation to 254 consenting primary care clinicians attending a
      medical meeting at 1 of 6 sites. A control group of 112 comparable physicians who
      did not attend the presentation completed the same questionnaire. Prepresentation
      scores of attendees were compared to scores of nonattendees to assess the
      generalizability of results. Prepresentation scores on selected questions were
      used to assess participant baseline knowledge, attitudes, and beliefs. Pre- and
      postpresentation scores for attendees at all sites were compared using the Mantel
      Haenszel statistic to assess the effectiveness of the BRAINSTORM CME. Pre- and
      postpresentation scores were compared by site using the Breslow-Day test to
      evaluate any differential impact based on CME location. RESULTS: Prepresentation
      scores of attendees and nonattendees were found to be similar. No significant
      difference in performance was noted across sites. A chi-square analysis revealed
      a statistically significant difference between pre- and postpresentation scores
      for 16 of the test's 20 questions. In the pretest, all participants scored <66%
      on 2 questions related to prevalence, impact, and pathophysiology of migraine, 2
      questions pertaining to history taking/physical examination, and 3 migraine
      management questions. Attendee scores improved to >66% posttest on all except 2
      questions related to prevalence, impact, and pathophysiology of migraine.
      CONCLUSION: Our results indicate that PCPs need to acquire greater understanding
      about the epidemiology and pathophysiology of migraine and may require guidance
      in history taking and physical examination of migraine patients. Improvement in
      scores posttest confirms that the BRAINSTORM program has a significant immediate
      impact on the knowledge, beliefs, and attitudes of participants. The program
      could be strengthened to improve emphasis in some areas where posttest scores
      showed no improvement.

PMID- 16643576
TI  - Factors influencing migraineur-consulting behavior in a university population.
AB  - OBJECTIVE: The purpose of this study was to identify factors that contribute to
      treatment-seeking behavior in migraineurs in a large employer population.
      Specifically, the impact of psychographic variables, such as social support,
      attitudes toward medication, locus of control, and migraine-associated
      disability, are considered concomitantly with demographic and disease severity
      variables. BACKGROUND: Migraine remains an underconsulted condition. Previous
      explorations of demographic factors and headache characteristics have not
      adequately predicted migraineur physician-consulting behavior. METHODS:
      University employees and students experiencing headaches were interviewed by
      pharmacists to determine whether they suffer from migraine using the
      International Headache Society (IHS) criteria for migraine. Identified
      migraineurs were categorized into 3 groups: (1) never-consulter, (2) lapsed
      consulter, and (3) current-consulter. Each group was asked to complete an
      instrument that assesses perceived social support (Headache Social Support
      Questionnaire), medication attitudes (Beliefs about Medicines Questionnaire),
      locus of control (Headache-Specific Locus of Control Scale), and migraine
      associated disability (Migraine Disability Assessment Questionnaire). Univariate
      (ANOVA) and multivariate (logistic regression) approaches were used to identify
      factors associated with migraineur-consulting behavior. RESULTS: A total of 100
      subjects participated in the study. Eighty-two participants met IHS criteria for
      migraine, of whom 22 were never-consulters, 20 were lapsed-consulters, and 40
      were current-consulters. The consulter groups differed on scores acquired from
      the Social Support Active Involvement subscale (P= .04) and the Healthcare
      Professional Locus of Control subscale (P= .010). The logistic regression
      procedures confirmed the contributions of social support and healthcare locus of
      control in predicting migraineur-consulting behavior. CONCLUSION: Results suggest
      that attitudes concerning the role of healthcare professionals and the presence
      of a supportive social network have greater influence on migraineur-consulting
      behavior than do patient demographic characteristics, beliefs about medications,
      and migraine frequency and severity. With an understanding of the link between
      psychosocial variables and consulting behavior, healthcare professionals may be
      able to positively impact migraineur physician consultation rates, drug therapy,
      and quality of life.

PMID- 16643577
TI  - Migraine prevention: what patients want from medication and their physicians (a
      headache specialty clinic perspective).
AB  - OBJECTIVE: To document the results of a migraine patients survey, from a headache
      specialty clinic, in which patients were asked to rank, in order of importance,
      certain characteristics of migraine preventive treatment. METHODS: A 10-question
      survey was completed by 150 patients (114 females and 36 males) with a history of
      migraine who presented to the Michigan Head Pain & Neurological Institute. The
      patients were asked to rank, in order of importance, characteristics of migraine
      preventive treatment. Each characteristic was rated individually on a 1 to 10
      scale (1 being of little importance and 10 being extremely important). The mean
      rating of each characteristic was then calculated and the results analyzed.
      RESULTS/DISCUSSION: From this migraine preventive treatment survey, the most
      important thing to migraineurs, from a headache specialty clinic population, is
      that the prescribing physician involves them in the decision making of choosing a
      preventive agent. The physician taking time to explain the possible medication
      side effects is the second most highly ranked characteristic. Migraine
      preventives with published efficacy in the medical literature are also deemed
      very important. Migraineurs do not mind using more than 1 preventive agent at one
      time if greater efficacy can be achieved. Agents that may affect weight and/or
      cause sedation may be important factors as to why patients (especially females)
      may not want to take a preventive medication. Natural therapies and once-daily
      dosing are ranked lower overall but still are important characteristics of
      preventive treatment. Some gender differences are noted in the ranking of
      migraine preventive characteristics.

PMID- 16643578
TI  - Migraine care among different ethnicities: do disparities exist?
AB  - OBJECTIVE: Evaluate whether, in a primary care setting, Caucasians (C) and
      African Americans (AA) with moderately to severely disabling migraines differed
      in regards to: utilizing the health-care system for migraine care, migraine
      diagnosis and treatment, level of mistrust in the health-care system, perceived
      communication with their physician, and perceived migraine triggers. BACKGROUND:
      Research has documented ethnic disparities in pain management. However, almost no
      research has been published concerning potential disparities in utilization,
      diagnosis, and/or treatment of migraine. It is also important to consider whether
      ethnic differences exist for trust and communication between patients and
      physicians, as these are essential when diagnosing and treating migraine.
      METHODS: Adult patients with headache (n = 313) were recruited from primary care
      waiting rooms. Of these, 131 (AA = 77; C = 54) had migraine, moderate to severe
      headache-related disability, and provided socioeconomic status (SES) data.
      Participants completed measures of migraine disability (MIDAS), migraine health
      care utilization, diagnosis and treatment history, mistrust of the medical
      community, patient-physician communication (PPC), and migraine triggers. Analysis
      of covariance (controlling for SES and recruitment site), chi-square, and Pearson
      product moment correlations were conducted. RESULTS: African Americans were less
      likely to utilize the health-care setting for migraine treatment (AA = 46% vs. C
      = 72%, P < .001), to have been given a headache diagnosis (AA = 47% vs. C = 70%,
      P < .001), and to have been prescribed acute migraine medication (AA = 14% vs. C
      = 37%, P < .001). Migraine diagnosis was low for both groups, and <15% of all
      participants had been prescribed a migraine-specific medication or a migraine
      preventive medication despite suffering moderate to severe levels of migraine
      disability. African Americans had less trust in the medical community (P < .001,
      eta2 = 0.26) and less positive PPC (P < .001, eta2 = 0.11). Also, the lower the
      trust and communication, the less likely they were to have ever seen (or
      currently be seeing) a doctor for migraine care or to have been prescribed
      medication. CONCLUSIONS: Migraine utilization, diagnosis, and treatment were low
      for both groups. However, this was especially true for African Americans, who
      also reported lower levels of trust and communication with doctors relative to
      Caucasians. The findings highlight the need for improved physician and patient
      education about migraine diagnosis and treatment, the importance of cultural
      variation in pain presentation, and the importance of communication when
      diagnosing and treating migraine.

PMID- 16643579
TI  - Medications associated with probable medication overuse headache reported in a
      tertiary care headache center over a 15-year period.
AB  - OBJECTIVES: To evaluate the substances associated with medication overuse
      headache (MOH) in a headache center, over the course of the past 15 years.
      BACKGROUND: The acute treatment of migraine has substantially changed over the
      past 15 years, and therefore, the substances associated with MOH may have changed
      as well. METHODS: We randomly reviewed charts of subjects seen during the years
      of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since
      the criteria proposed by the second edition of the International Classification
      of Headache Disorders require causal attribution, demonstrated by improvement
      after withdrawal (and this was not assessed in this study), herein we refer to
      probable MOH (PMOH). We contrasted the substances associated with PMOH over the
      studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of
      interest. The proportions of subjects with a diagnosis of PMOH remained stable
      over the years, varying from 64% of all cases seen in the center in 1990, to
      59.3% in 2005. We found a significant decrease in the relative frequency of
      probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in
      probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001).
      The differences were not significant for opioid overuse headache. The relative
      frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001),
      simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute
      medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute
      medications remains an important problem in the tertiary care arena, the
      substances associated with the overuse have dramatically changed over the past 15
      years. Educational initiatives should emphasize that the newer specific acute
      migraine medications (triptans) may also be associated with PMOH.

PMID- 16643580
TI  - Acute migraine treatment: patterns of use and satisfaction in a clinical
      population.
AB  - BACKGROUND: The sequence and timing of taking migraine medications, whether
      prescription or over-the-counter, and the patient's response to their treatment,
      is unknown. OBJECTIVE: To describe the use of, response to, and satisfaction with
      acute medications for 1 migraine attack. METHODS: We performed a clinic-based
      survey of 127 patients at Jefferson Headache Center, Philadelphia. Adult patients
      who met the International Headache Society criteria for migraine with or without
      aura were included in the study. Patients were asked to complete a questionnaire.
      RESULTS: Of 109 participants who met the inclusion criteria, most waited 1 hour
      or more after the onset of symptoms to take medication. Triptans were most
      commonly used as first, second, and third medications. Triptan use was associated
      with higher 2-hour pain-free response rates compared with other agents, whether
      the triptan was used as the first, second, or third medication. Patients who were
      treated with medications other than triptans were more likely to have pain at 2
      hours (P = .36). NSAIDs had relatively low pain-free and headache relief response
      rates at 2 hours. Sixty-two participants (56.9%) had to treat a second time and
      31 (28.4%) had to treat a third time. Some participants (17.6%) had headache
      recurrence within 24 hours after becoming headache free following initial
      medication and some (23.5%) had recurrence after becoming headache free following
      their second medication. Sixty-six percent of participants reported being very
      satisfied/satisfied with their initial medication and 33% were somewhat
      dissatisfied/dissatisfied to some degree. Even though most patients were
      satisfied with their medication, 88% reported that they would be willing to try a
      new antimigraine medication. Most patients (60 [55%]) preferred a long-acting
      agent versus a rapid-onset, short-acting agent (which was preferred by 49 [45%]
      patients). CONCLUSION: Migraine patients have treatment preferences. They
      generally want a drug that provides complete headache relief, and they are often
      satisfied with the current treatment options.

PMID- 16643581
TI  - Haloperidol in the acute treatment of migraine: a randomized, double-blind,
      placebo-controlled study.
AB  - OBJECTIVE: To assess the efficacy and safety of i.v. haloperidol in treatment of
      acute migraine headache in a double-blind, randomized, placebo-controlled study
      design. BACKGROUND: Neuroleptics are mainly used as antiemetics in acute
      migraine. In a previous open trial haloperidol was effective in relieving
      migraine pain. DESIGN: Patients were randomized into 2 groups receiving
      intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of
      normal saline alone. Pain was assessed by visual analogue scale (VAS) before and
      1 to 3 hours after the infusion. If the patient felt no relief in pain intensity
      1 to 3 hours after the infusion and had received placebo, he/she then received
      haloperidol infusion as an open trial. The open trial also included 7 patients
      who refused from the placebo-controlled trial. About 1 month after the infusion
      the patients were contacted by telephone and interviewed about the side effects
      of the treatment. RESULTS: Forty patients were enrolled into the double-blind,
      placebo-controlled study. Before the infusion the VAS values were 7.7 in the
      haloperidol and 7.2 in the placebo group. After the infusion the VAS values were
      2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain
      relief was achieved in 80% of the patients treated with haloperidol, whereas only
      3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated
      with placebo without response together with 7 patients who refused from the
      placebo-controlled study participated in the open trial. In this group VAS
      declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief.
      The most common side effects caused by haloperidol were sedation and akathisia,
      the latter being more troublesome. These effects were very common in patients
      participating in the double-blind (80%) and open (88%) trials. Sixteen percent of
      the patients considered the side effects intolerable and would not like the
      migraine attacks to be treated with haloperidol in the future. Three patients
      (7%) returned to the emergency ward because of a relapse. CONCLUSIONS: This study
      shows that i.v. haloperidol is very effective in relieving migraine-associated
      pain. Because the majority of the patients had taken other medication without
      response, haloperidol appears to be an effective rescue medication even when
      other types of treatment have failed. Relapses are rare, but side effects are
      common, limiting the use of haloperidol in some patients.

PMID- 16643582
TI  - Use of a pine bark extract and antioxidant vitamin combination product as therapy
      for migraine in patients refractory to pharmacologic medication.
AB  - OBJECTIVE: To evaluate the potential benefit of a pine bark extract and
      antioxidant vitamin combination product in the treatment of migraine headache.
      BACKGROUND: This was an uncontrolled preliminary study to investigate the
      potential of an antioxidant formulation as therapy for migraine headache.
      METHODS: Twelve patients with a long-term history of migraine with and without
      aura who had failed to respond to multiple treatments with beta-blockers,
      antidepressants, anticonvulsants, and 5-hydroxytryptamine receptor agonists were
      selected for the study. They were treated with 10 capsules of an antioxidant
      formulation of 120 mg pine bark extract, 60 mg vitamin C, and 30 IU vitamin E in
      each capsule daily for 3 months. Following enrollment patients completed a
      migraine disability assessment (MIDAS) questionnaire to give a baseline measure
      of migraine impact on work, school, domestic, and social activities over the
      previous 3 months. Patients were then treated for 3 months with the antioxidant
      formulation while continuing to receive existing pharmacologic medications. A
      second MIDAS was given at the conclusion of the treatment period. RESULTS: There
      was a significant mean improvement in MIDAS score of 50.6% for the 3-month
      treatment period compared with the 3 months prior to baseline (P < .005). The
      treatment was also associated with significant reductions in number of headache
      days and headache severity score. Mean number of headache days was reduced from
      44.4 days at baseline (95% CI 28.9 to 59.8) to 26.0 days (95% CI 5.3 to 46.7; P <
      .005) after 3 months' therapy and mean headache severity was reduced from 7.5 of
      10 (95% CI 6.7 to 8.4) to 5.5 (95% CI 4.1 to 7.0; P < .005). CONCLUSION: These
      data suggest that the antioxidant therapy used in this study may be beneficial in
      the treatment of migraine possibly reducing headache frequency and severity.
      Further clinical investigation into the efficacy of antioxidant as therapy for
      chronic migraine is warranted.

PMID- 16643583
TI  - Migraine headaches and preeclampsia: an epidemiologic review.
AB  - OBJECTIVE: To summarize and evaluate available empirical research on the
      relationship between migraines and gestational hypertension or preeclampsia and
      to provide direction for future research in this area. BACKGROUND: Migraines
      affect a substantial proportion of reproductive-aged women and have been
      associated with cardiovascular risk factors and ischemic disease in this
      population. Preeclampsia is a vascular disorder of pregnancy, also linked to
      adverse cardiovascular outcomes. METHODS: Publications were identified by a
      MEDLINE search using keywords "migraine,""preeclampsia," and "gestational
      hypertension," and by examination of the reference lists of identified articles.
      RESULTS: The literature review yielded 10 studies addressing the association
      between migraines and preeclampsia or gestational hypertension. Of the 10
      studies, 8 reported a positive association between the syndromes. CONCLUSIONS:
      Available evidence suggests that migraines and preeclampsia may reflect an
      underlying predisposition toward ischemic injury. More rigorous epidemiologic
      research is warranted, after consideration of several important methodologic
      issues.

PMID- 16643584
TI  - Zonisamide prophylaxis in refractory pediatric headache.
AB  - INTRODUCTION: Currently, no medications are approved for pediatric headache
      prophylaxis in the United States. Zonisamide is an antiepileptic drug with
      preliminary studies suggesting some efficacy in the adult headache population.
      METHODS: A retrospective chart review was conducted on refractory headache
      patients in our multidisciplinary Headache Clinic who were treated with
      zonisamide, an antiepileptic drug, for headache prophylaxis. Records were
      reviewed for pertinent data including patient history, diagnosis, prior treatment
      regimens, and zonisamide response, along with headache frequency. RESULTS: Twelve
      patients were identified (8 girls); mean age was 13.5 years. Eight of the 12
      patients had a positive response to zonisamide with greater than 50% reduction in
      headaches from pretreatment values. CONCLUSION: Zonisamide had some efficacy in
      headache reduction. It was well tolerated with only minor side effects. Further
      prospective studies with zonisamide are warranted in refractory pediatric
      headache patients.

PMID- 16643585
TI  - Subacutely progressive epidural hematoma in the absence of a "lucid interval".

PMID- 16643586
TI  - Postictal headache and migraine.

PMID- 16643587
TI  - Lung cancer presenting with unilateral facial pain: remission after laryngeal
      nerve palsy.
AB  - A 39-year-old woman presented with a 2-month history of intractable, left-sided
      facial pain. A CT scan of the thorax disclosed a large lung mass surrounding
      supra-aortic vessels and hilus. The symptoms underwent a rapid and spontaneous
      remission after laryngeal nerve palsy with dysphonia developed. Referred facial
      pain secondary to the compression of the vagus nerve can rarely be the first
      manifestation of an underlying lung cancer. All cases of unexplained unilateral
      facial pain should be investigated for a mediastinal pathology, especially in
      smoker subjects.

PMID- 16643588
TI  - Reversible palinopsia and the Alice in Wonderland syndrome associated with
      topiramate use in migraineurs.
AB  - Two patients are reported who developed palinopsia while taking topiramate for
      migraine prevention which resolved or decreased in frequency or duration on lower
      doses, but recurred or increased in frequency or duration on higher doses. Both
      patients had complete resolution of palinopsia when topiramate was discontinued.
      A third patient is described who developed the "Alice in Wonderland" syndrome
      about 1 week after starting topiramate for migraine prevention with complete
      resolution of symptoms about 1 month after stopping. Topiramate use may cause
      palinopsia and may be associated with the Alice in Wonderland syndrome through an
      unknown mechanism.

PMID- 16643589
TI  - Efficacy of therapeutic intervention in headache units in patients with frequent
      headaches: the EFUNCE study.
AB  - Data confirming that therapeutic intervention in headache units is superior to
      care received by patients in other levels of the health system are scant. This is
      a pilot study that includes patients seen in 4 headache units for at least 1
      year, who had a headache frequency of more than 15 days per month. The results of
      the first 30 patients showed a significant improvement in different headache
      parameters and a high degree of satisfaction with the treatment received.

PMID- 16643592
TI  - Review of animal models for autism: implication of thyroid hormone.
AB  - Autism is a behaviorally defined disorder associated with characteristic
      impairments in social interactions and communication, as well as restricted and
      repetitive behaviors and interest. Its prevalence was once thought to be
      2/10,000, but recently several large autism prevalence reviews revealed that the
      rate of occurrence was roughly 30/10,000. While it has been considered a
      developmental disorder, little is certain about its etiology. Neuroanatomical
      studies at the histological level in the brains of autistic patients provide many
      arguments in the etiology of autism. Results from postmortem and imaging studies
      have implicated many major structures of the brain including the limbic system,
      cerebellum, corpus callosum, basal ganglia and brainstem. There is no single
      biological or clinical marker for autism. While several promising candidate genes
      have been presented, the critical loci are yet unknown. Environmental influences
      such as rubella virus, valproic acid, and thalidomide exposure during pregnancy
      are also considered important, as concordance in monozygotic twins is less than
      100% and the phenotypic expression of the disorder varies widely. It is thus
      hypothesized that non-genetic mechanisms contribute to the onset of autistic
      syndrome. In light of these ambiguities, hope is held that an animal model of
      autism may help elucidate matters. In this article, we overview most of the
      currently available animal models for autism, and propose the rat with mild and
      transient neonatal hypothyroidism as a novel model for autism.

PMID- 16643593
TI  - Micro-focus X-ray computed tomography images of the 3D structure of the cranium
      of a fetus with asymmetric double malformation.
AB  - Reconstructed micro computed tomography (Micro-CT, micro-CT) images have revealed
      the detailed three-dimensional structure of the cranium of human fetal congenital
      anomalies for the first time. The objects were a head and a cervix of female
      autosite and a parasite consisting of only a head conjoined to the scapular
      region of the autosite of an asymmetric double malformation (asymmetric conjoined
      twins, heteropagus twinning) at a gestational age of 8 months. The cranium of the
      autosite was normal, but that of the parasite was characterized by otocephaly
      (agnathia, synotia, and monorhina) and almost all the cranial bones were of an
      abnormal shape. It is suggested that a part of occipital bone (the basioccipital
      and exoccipital bones), the vomer and cribriform plate were absent and this
      resulted in the fusion and overlapping of bilateral temporal and craniofacial
      bones that should have been adjacent to them. This resulted in a reformation and
      relocation of most of the cranial bones. Micro-CT is a useful tool to visualize
      the detailed bone structure which has not been clarified by the conventional
      dissection methods and other imaging technologies and is a powerful instrument
      for studying congenital anomalies.

PMID- 16643594
TI  - Leptin deficiency causes pycnotic change in fetal cingulate cortical cells.
AB  - Leptin is an obese gene product, and leptin-deficient ob/ob mice develop
      hyperphagia and reduced locomotor activity. Leptin is thought to be related to
      brain development, because leptin receptors are widely expressed in the brain,
      and because brain weight as well as brain protein and DNA contents were reduced
      in adult ob/ob mice. In this study, we investigated the effect of leptin on the
      fetal cingulate cortex, since the leptin receptor is expressed in the neurons of
      the cingulate cortex, which is involved in emotion as well as in sensory, motor,
      and cognitive processes. The ob/ob fetuses had more pycnotic cells than wild-type
      fetuses in the cingulate cortex at embryonic day (E) 18. Many pycnotic cells were
      observed in the intermediate zone of the cingulate cortex. Most cells observed in
      this area were neuronal lineage cells, while few undifferentiated cells and
      oligodendrocyte precursor cells were found. At E18 there was no significant
      difference in the rostrocaudal length of the corpus callosum, which contains the
      neuronal projection from the cingulate cortex, between ob/ob and wild-type
      fetuses. We also showed that the length of the cerebrum was greater and the width
      of the cerebrum and cerebellum were lesser in ob/ob fetuses than in wild-type at
      E16. These results suggest an increased cell death in neuronal lineage cells in
      the intermediate zone of the cingulate cortex in leptin-deficient ob/ob mice.
      Leptin deficiency may also alter the gross morphology of the brain in
      development, but not the formation of the corpus callosum.

PMID- 16643595
TI  - Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: a
      morphological in vivo study.
AB  - It is well-known that TCDD (2,3,7,8, tetrachloridedibenzo-p-dioxin) induces cleft
      palates (CPs) in pregnant C57BL mice. However, it is unclear if TCDD is a
      possible teratogen for cleft lip. We examined maxillofacial malformations
      including cleft lip in three animal strains: A/J mice, C57BL/6J mice and ICR
      mice. The A/J mouse develops cleft lip and palate spontaneously at a 5-10% rate.
      TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes
      at 10 microg/kg, 20 microg/kg, or 40 microg/kg to examine the dose-response, and
      on a single day from GD 8.5-14.5 to examine the timing effects of TCDD
      administration on lip and palate formation. Furthermore, the palatal shelf
      movements during GD 8.5-14.5 were observed with a stereoscopic microscope. All
      embryos had cleft palates when the TCDD was administered just before
      palatogenesis (GD11.5-GD12.5). With respect to the TCDD effects, there were large
      differences among the strains. In the A/J mice, the difference between a lethal
      dose and a dose that could induce a cleft palate was close. Cleft lips were not
      induced, even when the TCDD was given just before labiogenesis. Morphologically,
      both palatal shelves contacted perfectly along their lengths, but separated and
      formed cleft palates. In conclusion, TCDD is a strong inducer of cleft palates,
      and interferes with the fusion phase of the secondary palate, but has no effect
      on the lip.

PMID- 16643596
TI  - Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with
      that of young rats.
AB  - Newborn rat studies were conducted with oral administration of 3-ethylphenol
      (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of
      no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL)
      with those from 28-day studies of young rats starting at 5-6 weeks of age. In the
      newborn rat studies, slightly lowered body weight was observed after 3EP
      treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed
      righting reflex were clearly observed after 4EP treatment. In the young rat
      studies, salivation, staggering gait, changes in the liver including high values
      of liver weight and alanine aminotransferase or total cholesterol and the lesions
      in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of
      3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than
      those in the young rat studies. As a clear toxicity of 3EP was not observed in
      newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young
      rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats
      were 3-5 times more susceptible to 3EP and 4EP than young rats.

PMID- 16643597
TI  - In vitro embryotoxicity testing of metals for dental use by differentiation of
      embryonic stem cell test.
AB  - We examined embryotoxicity using the embryonic stem cell test (EST) protocol.
      Tests were conducted using standard reagents for the atomic absorption
      measurement of 11 metal ions, silver, cobalt, chromium, copper, mercury, nickel,
      palladium, antimony, tin, vanadium, and zinc from among metals comprising dental
      alloys. In addition, for four metals like silver, cobalt, chromium, and nickel,
      the tests were also conducted using a test solution extracted from powder in the
      cell culture medium. The embryotoxic potential was obtained from a biostatistics
      based prediction model, which was calculated from three endpoints, the ID50,
      IC50ES and IC(50)3T3. Data with the standard reagents showed that chromium and
      mercury ions corresponded to class 3, that is, having a strong embryotoxicity,
      while antimony, tin, and vanadium ions exhibited a weak embryotoxicity. The other
      metal ions demonstrated no embryotoxicity. On the other hand, when extracts of
      metal powder in cell culture solutions were used, silver exhibited a weak
      embryotoxicity while all other metals exhibited no embryotoxicity. In the future,
      it will be important to clarify the embryotoxicity of the many dental materials
      that are in use today. In addition, it is necessary to develop substances to
      ensure they have no toxicity before use in dental applications.

PMID- 16643598
TI  - Population-based case-control study of oxoline acid use during pregnancy for
      birth outcomes.
AB  - The objective of the study was to check the effect of oxoline acid, a
      bactericidal drug for the treatment of urinary tract infection during pregnancy,
      on congenital abnormalities of informative offspring and fetal development. Human
      data of oxoline acid use during pregnancy have not been reported, but the use of
      this quinolone derivative is not recommended during pregnancy by the US Food and
      Drug Administration. The teratogenic and fetotoxic potential of oxoline acid was
      evaluated in the population-based large data set of the Hungarian Case-Control
      Surveillance of Congenital Abnormalities between 1980 and 1996. Observed and
      expected numbers of congenital abnormalities were compared in the newborn infants
      and fetus of case mothers with oxoline acid treatment. In addition, gestational
      age and birthweight were evaluated in control newborn infants born to mothers
      with or without oxoline acid treatment. Of 38,151 newborn infants without any
      congenital abnormalities (control group), 13 (0.03%) had mothers who were treated
      with oxoline acid, while of 22,843 cases with congenital abnormalities, five
      (0.02%) had mothers who were treated with oxoline acid during pregnancy (POR with
      95% CI: 0.6, 0.2-1.8). The comparison of observed and expected number of
      different congenital abnormalities did not show the teratogenic potential of
      oxoline acid. There was a 0.9 weak shorter gestational age without a smaller
      birthweight in the newborn infants born to mothers with oxoline acid treatment.
      Our data did not indicate teratogenic and fetotoxic effect of oxoline acid,
      however, the number of cases and controls was limited.

PMID- 16643599
TI  - Effects of maternal uninephrectomy on the development of fetal rat kidney:
      apoptosis and the expression of oncogenes.
AB  - The present study was designed to explore whether maternal uninephrectomy affects
      development of the collecting ducts in fetal kidney. Localization of DNA
      fragmented cells in the kidney of fetal rats from uninephrectomized mothers were
      examined by the terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin
      nick end labeling (TUNEL) method. Immunohistochemistry was used to examine the
      localizations of bcl-2 gene products. The gene expressions for bcl-2, p53, and
      WT1 mRNAs were examined by using the semi-quantitative reverse transcript
      polymerase chain reaction. TUNEL positive cells were more numerous in the
      medullary collecting ducts of the fetuses from uninephrectomized mothers than in
      those of the fetuses from sham-operated ones. The expressions of bcl-2, p53, and
      WT1 mRNAs were lower in the fetuses from uninephrectomized mothers than in the
      fetuses from sham-operated ones. Cells in the medullary collecting ducts showed
      positive reactions to anti-bcl-2 gene products antibody with the reactions being
      weaker in the fetuses from uninephrectomized mothers. These results showed that
      maternal uninephrectomy accelerated the development of fetal rat kidney and it
      was associated with the lowered the expression of bcl-2 in fetal rat kidney.

PMID- 16643601
TI  - Cloned mice and embryonic stem cell establishment from adult somatic cells.
AB  - Cloning methods are now well described and becoming routine. Yet the frequency at
      which cloned offspring are produced remains below 2% irrespective of nucleus
      donor species or cell type. Especially in the mouse, few laboratories can make
      clones from adult somatic cells, and most mouse strains never succeed to produce
      cloned mice. On the other hand, nuclear transfer can be used to generate
      embryonic stem (ntES) cell lines from a patient's own somatic cells. We have
      shown that ntES cells can be generated relatively easily from a variety of mouse
      genotypes and cell types of both sexes, even though it may be more difficult to
      generate clones directly. Several reports have already demonstrated that ntES
      cells can be used in regenerative medicine in order to rescue immune deficient or
      infertile phenotypes. However, it is unclear whether ntES cells are identical to
      fertilized embryonic stem (ES) cells. In general, ntES cell techniques are
      expected to be applicable to regenerative medicine, however, these techniques can
      also be used for the preservation of the genetic resources of mouse strains
      instead of preserving such resources in embryos, oocytes or spermatozoa. This
      review seeks to describe the phenotype, application, and possible abnormalities
      of cloned mice and ntES cell lines.

PMID- 16643602
TI  - Bioreactors for 3-dimensional high-density culture of human cells.
AB  - A bioreactor was developed as an instrument to culture human or animal cells that
      require attachment in a large quantity or at a high density. The purpose for
      developing such a bioreactor is two-fold: to produce a large quantity of animal
      or human cells that have been modified by gene recombination technology to
      accommodate manufacture of physiologically-active substances or human proteins on
      an industrial scale; and for research to culture animal cells to form a high
      density 3-dimensional structure as a morphological or functional tissue or organ
      entity. In the current report, the circulatory flow bioreactor and radial flow
      bioreactor (RFB) are introduced, in which the former can be scaled up. As a small
      bioreactor produced for the latter purpose, a rotary cell culture system and
      novel multicoaxial hollow-fiber bioreactor are introduced. Finally, a small RFB
      culture system that was scaled down by the present author and his collaborators
      for the study of a 3-dimensional high density culture system is described. The
      RFB can be readily scaled up for manufacturing or scaled down for research
      purposes. This is a cell culturing system that can induce the functions of human
      tissues by preparing a high density 3-dimensional organization of cells of human
      origin.

PMID- 16643603
TI  - Large DNA palindromes as a common form of structural chromosome aberrations in
      human cancers.
AB  - Breakage-fusion-bridge cycles contribute to chromosome aberrations and generate
      large DNA palindromes that facilitate oncogene amplification in cancer cells. At
      the molecular level, large DNA palindrome formation is initiated by chromosome
      breaks, and genomic architecture such as short inverted repeat sequences
      facilitates this process in mammalian cells. However, the prevalence of DNA
      palindromes in cancer cells is currently unknown. To determine the prevalence of
      DNA palindromes in human cancer cells, we have developed a new microarray-based
      approach called Genome-wide Analysis of Palindrome Formation (GAPF, Tanaka et
      al., Nat Genet 2005; 37: 320-7). This approach is based on a relatively simple
      and efficient method to purify "snap-back DNA" from large DNA palindromes by
      intramolecular base-pairing, followed by elimination of single-stranded DNA by
      nuclease S1. Comparison of Genome-wide Analysis of Palindrome Formation profiles
      between cancer and normal cells using microarray can identify genome-wide
      distributions of somatic palindromes. Using a human cDNA microarray, we have
      shown that DNA palindromes occur frequently in human cancer cell lines and
      primary medulloblastomas. Significant overlap of the loci containing DNA
      palindromes between Colo320DM and MCF7 cancer cell lines suggests regions in the
      genome susceptible to chromosome breaks and palindrome formation. A subset of
      loci containing palindromes is associated with gene amplification in Colo320DM,
      indicating that the location of palindromes in the cancer genome serves as a
      structural platform that supports subsequent gene amplification.

PMID- 16643604
TI  - Cancer stem cells in human gastrointestinal cancers.
AB  - The concept of cancer stem cell has developed in leukemia. Recently, it has
      expanded to include solid tumors such as brain or breast tumors. However, the
      descriptions are not recognized in human gastrointestinal cancers. We used flow
      cytometry and the DNA-binding dye (Hoechst 33342) to isolate side population (SP)
      cells from various human gastrointestinal system cancer cell lines. The SP cell
      fraction is considered to contain abundant stem cells. Fifteen of 16 cancer cell
      lines from the gastrointestinal system contained 0.3-2.2% SP cells. We studied
      the characteristics of the SP cells in hepatic or colon cancer cell lines. The
      results demonstrated that cancers of the gastrointestinal system do contain SP
      cells that show some characters of so-called stem cells. In this paper, we report
      our study results with a review of the literature.

PMID- 16643605
TI  - Refinement of cytokine use in the in vitro expansion of erythroid cells.
AB  - Blood transfusion is indispensable for many clinical applications. However, the
      supply of transfusable material is insufficient in many countries. Human cord
      blood contains many hematopoietic stem and progenitor cells, providing a
      promising resource for the production of transfusable material in vitro. In this
      study, we have refined a protocol to produce abundant red blood cells (RBC) from
      human cord blood in an in vitro culture system. We found that erythropoietin and
      interleukin-3 were most effective when they were added to the culture medium
      sequentially rather than simultaneously. Although insulin-like growth factor-I
      (IGF-1) has been reported to function as a positive regulator of RBC production
      in some in vitro culture systems, we found that IGF-1 had a negative effect upon
      RBC production. However, IGF-II appeared to function as a positive regulator of
      RBC production. Finally, stem cell factor functioned to both expand and
      accelerate the differentiation of immature erythroid cells.

PMID- 16643606
TI  - Human endometrial cytodifferentiation by histone deacetylase inhibitors.
AB  - Abstract Human uterine endometrium repeats proliferation, differentiation
      (decidualization) and tissue breakdown during the menstrual period. Appropriate
      secretion of ovarian steroid hormones regulates these sequential endometrial
      remodeling cycles. While progesterone replacement therapy is adopted for
      endometrial dysfunction of differentiation, including recurrent impairment of
      implantation, no obvious effective results are obtained. Histone reversible
      acetylation, regulated by histone acetyltransferases and histone deacetylases
      plays a pivotal role in gene transcription. Although, in cells cultured with
      histone deacetylase inhibitors (HDACI), the expression of only about 2% of
      expressed genes is changed twofold or more compared with untreated control cells.
      Numerous previous works have demonstrated that HDACI affect cell
      proliferation/apoptosis in a variety of types of cells. To date, several HDACI
      are in phase I or phase II clinical trials as anticancer drugs. However, no
      reports have been found that HDACI is useful for transdifferentiation in human
      endometrium. Recently, we reported that HDACI could induce the expression of
      differentiation marker proteins, morphological change and functional
      cytodifferentiation in both human endometrial stromal and epithelial cells. In
      this review, we summarize the effect of HDACI against the human endometrial
      cytodifferentiation, indicating the possibility that HDACI can be used not only
      as an anticancer drug, but also as a transdifferentiation reagent, based on a new
      strategy.

PMID- 16643607
TI  - Essential role for gene profiling analysis in the authentication of human cell
      lines.
AB  - Cross-contamination between cultured cell lines can result in the generation of
      erroneous scientific data. Hence, it is very important to eliminate cell lines
      that are of an origin different from that being claimed. Inter-species
      contamination can be detected by various established methods, such as karyotype
      and isozyme analyses. However, it has been impossible to detect intraspecies
      cross-contamination prior to the development of technology to detect differences
      between cell lines at the molecular level. Recently, profiling of short tandem
      repeat (STR) polymorphisms has been established as a method for the analyses of
      gene polymorphism. Gene profiling by STR polymorphism (STR profiling) is a simple
      and reliable method to identify individual cell lines. Each human cell line
      currently provided by the Cell Engineering Division of the RIKEN BioResource
      Center was analyzed by STR profiling to authenticate its identity. We found that
      more than 10 human cell lines out of approximately 400 were in fact identical to
      a different cell line deposited in the collection, and therefore had been
      misidentified. We conclude that STR profiling is a useful and powerful method for
      eliminating cell lines that have been misidentified by cross-contamination or by
      other causes. Hence, STR profiling of human cell lines used in published research
      will likely be a prerequisite for publication in the future, so that the problem
      of misidentification of cell lines can be eliminated.

PMID- 16643608
TI  - Urinary macromolecules and renal tubular cell protection from oxalate injury:
      comparison of normal subjects and recurrent stone formers.
AB  - AIM: To determine whether urinary macromolecules (UMM), which are the high
      molecular weight substances in urine, can provide protection against the oxalate
      associated injury to the renal tubular cells. METHODS: UMM were extracted from 24
      h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male
      patients. Urine parameters in relation to urolithiasis were measured, including
      the level of glycosaminoglycans (GAG) in the UMM. Madin-Darby canine kidney
      (MDCK) cells were used to evaluate the protective activity of UMM from oxalate
      induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium
      (MTT) assay. RESULTS: Considering urinary parameters, citrate was significantly
      higher in urine from normal subjects than stone-former subjects; the other
      parameters show no differences between the groups. Total UMM and the level of GAG
      in the UMM were also significantly higher in the normal subject group. Compared
      with normal subject and stone-former subject UMM, after cells were treated with
      the UMM and then exposed to oxalate solution, LDH release was significantly
      higher in stone-former group. In the MTT assay, we found that more viable cells
      were observed after treatment with UMM compared to control in both groups.
      Moreover, UMM from the normal subjects showed higher protective activity against
      oxalate-related cytotoxicity than UMM from the stone-former subjects. CONCLUSION:
      UMM protected renal epithelial cells from oxalate-related injury. This protective
      activity was found to be higher in normal subject UMM than stone-former UMM.
      Among other factors, a higher concentration of GAG and citrate in normal subject
      UMM might affect some parts in this finding.

PMID- 16643609
TI  - Application of cardiopulmonary bypass for resection of renal cell carcinoma and
      adrenocortical carcinoma extending into the right atrium.
AB  - AIM: The application of cardiopulmonary bypass to atrial involvement represents
      an important advance that has improved the safety and technical efficacy of a
      difficult surgical undertaking. Our experiences of the management of extended
      thrombi into the right atrium in patients with retroperitoneal malignancy using a
      cardiopulmonary bypass were discussed. METHODS: Data were reviewed for five
      patients (two men and three women; mean age, 60.4 years; range, 49-79 years) with
      retroperitoneal tumors displaying intracardiac tumor extension. Tumors originated
      in the right kidney in four patients, and in left adrenal gland in one patient.
      Cardiopulmonary bypass was used in all cases. RESULTS: Mean total blood loss was
      6059 mL. Mean operative time was 14.7 h. No intra- or postoperative complications
      due to surgical technique were encountered, and no significant bleeding occurred
      during incision of the inferior vena cava or after removal of tumor thrombus. The
      follow-up period ranged from 3 to 20 months with a mean of 12.6 months. Of the
      five patients, three died of metastatic diseases, one died of liver dysfunction
      and one remains disease free as of 18 months postoperatively. CONCLUSIONS: Our
      experience indicates that this procedure can be safely used for atrial
      involvement. Although superior long-term survival cannot be shown yet, favorable
      early results and a lack of perioperative complications were identified.

PMID- 16643610
TI  - Laparoscopic ureterolithotomy: its role and some controversial technical
      considerations.
AB  - OBJECTIVE: To define the role of laparoscopic ureterolithotomy in the management
      of urolithiasis and evaluate the controversial techniques of this operation.
      METHODS: Between July 1997 and December 2004, retroperitoneoscopic
      ureterolithotomy was performed as a primary procedure in 30 patients who had
      either large or impacted stones in the upper ureter. The other indications were
      stones which could not be fragmented by shock wave lithotripsy or the patients
      could not afford the cost of shock wave lithotripsy. The mean (range) age of the
      patients was 44.07 years (17-78) and the mean (range) stone size was 19.03 mm (10
      40). The ureter was closed with intracorporeal laparoscopic suture without
      placing a stent. RESULTS: The stone was removed in all but one case. The mean
      (range) operative time was 121.38 min (75-270). No intraoperative complications
      were recorded. The mean (range) postoperative drain removal was 2.86 days (2-10).
      Postoperative complications included prolonged urinary leakage in one patient. On
      the sixth month of follow up, all patients were stone free without any evidence
      of ureteral stricture. CONCLUSION: Laparoscopic ureterolithotomy is a minimally
      invasive treatment and may be considered as the useful first-line management for
      large impacted upper ureteric stones. The technical recommendations were
      retroperitoneal access and suturing the ureterotomy incision. Ureteral stent
      should be placed in only cases of severe inflammation of the ureter or
      inappropriate suturing.

PMID- 16643611
TI  - Identification of autoantibodies elicited in a patient with prostate cancer
      presenting as dermatomyositis.
AB  - OBJECTIVES: Dermatomyositis is an uncommon autoimmune disease distinguished by
      proximal muscle weakness and a characteristic skin rash. Dermatomyositis has also
      frequently been associated with malignancy, typically heralding the diagnosis of
      ovarian, lung, gastric, or colorectal cancer. We report an unusual case of
      prostate adenocarcinoma preceded by a diagnosis of dermatomyositis. We
      hypothesized that in this particular patient, proteins produced by the neoplastic
      prostatic tissue, which might be normally expressed in muscle tissue, were
      immunologically recognized as autoantigens. METHODS: Serum from this patient was
      used to screen a cDNA lambda phage expression library from normal prostate tissue
      for prostate protein-specific IgG. RESULTS: We identified several immunoreactive
      plaques encoding known autoantigens, and several encoding known muscle-related
      proteins, including aldolase C, eukaryotic translation elongation factor 1 alpha
      1, transgelin, and acetyl-coenzyme A acyltransferase 1. IgG specific for these
      proteins were not specifically recognized in sera from other patients with
      prostate cancer compared with male control blood donors, and were not
      specifically recognized in a small panel of sera from patients with breast or
      ovarian cancer and dermatomyositis. CONCLUSIONS: Our results demonstrate that
      this patient with prostate cancer presenting as dermatomyositis had
      autoantibodies to specific proteins, possibly associated with his autoimmune
      myopathy. Moreover, given this patient's history and the multiple treatment
      options for prostate cancer, the identification of dermatomyositis in men should
      prompt an evaluation to exclude a concurrent diagnosis of prostate cancer.

PMID- 16643612
TI  - Three-year results of treatment for prostate cancer with low-dose rate temporary
      iridium-192 brachytherapy.
AB  - AIM: To report the 3-year treatment results of definitive irradiation by using a
      temporary interstitial implant with low-dose rate iridium-192 with or without
      external beam radiotherapy in the treatment of localized prostate cancer.
      METHODS: One-hundred and forty-three patients with pathologically defined
      prostate carcinoma were treated from December 1997 to April 2003. The patients
      were classified into a low-risk group (T2, PSA<or=20 ng/mL and Gleason
      score<or=6) or a high-risk group (T3, PSA>20 ng/mL or Gleason score>or=7). Low
      risk patients were treated with low-dose-rate iridium brachytherapy as
      monotherapy delivering 70 Gy. High-risk patients were treated with the
      combination of brachytherapy and external beam radiotherapy delivering 40 Gy and
      36 Gy, respectively. Kaplan-Meier estimates of prostate-specific antigen (PSA)
      progression-free survival rate were analysed. To assess the treatment quality in
      different periods, PSA progression-free survival rates in late era (year of 2000
      and after) and in early era (before 2000) were compared. Morbidity was graded
      according to the Radiation Therapy Oncology Group grading scale. RESULTS: One
      hundred and nineteen patients were analysed, of which 86 patients underwent
      monotherapy with an iridium implant, and 33 were treated with the combination of
      external beam radiotherapy. Twenty-four patients were excluded from the analysis
      because the classification of risk group did not suit the criteria. The total
      (n=119) PSA progression-free survival rate at 3 years was 80.3%. The PSA
      progression-free survival rate at 3 years for the monotherapy group (n=86) and
      the combination therapy group (n=33) were 78.2% and 86.9%, respectively. There
      were 23 patients who were followed for more than 36 to 63 months, and, during
      this period, only 1 patient who received the monotherapy was diagnosed as PSA
      failure at 50 months. The 3-year PSA progression-free survival rate of
      monotherapy in late era was significantly higher than that in early era; however,
      no significant difference was seen in the combination treatment. Morbidity for
      the combination treatment was low; however, for the monotherapy, three patients
      developed severe rectal ulcers, and colostomies were made. CONCLUSIONS: The PSA
      progression-free survival rate after low-dose rate iridium-192 brachytherapy with
      or without external beam radiotherapy can be satisfactory and longer follow up is
      necessary to compare the efficacy of other treatments.

PMID- 16643613
TI  - Is interval from an initial biopsy a significant predictor of prostate cancer at
      repeat biopsies?
AB  - BACKGROUND: Currently, there are no clear criteria for indicating repeat biopsies
      in patients with negative results at an initial biopsy of the prostate. The aim
      of the present study is to determine the clinical and pathological parameters
      which predict prostate cancer at repeat biopsies with special attention to the
      interval between biopsies in addition to prostate specific antigen (PSA) and its
      derivatives. METHODS: We reviewed 100 patients who underwent an initial biopsy
      that proved negative for prostate cancer and required repeat biopsies between
      November 1996 and November 2003. Clinical parameters such as age, PSA and its
      derivatives, interval between biopsies, number of cores taken and initial biopsy
      histology were analyzed. RESULTS: In total, 31 patients (31.0%) were found to
      have prostate cancer, 18 (25.7%) of 70 patients by the second biopsy and 13
      (46.4%) of 28 patients by the third biopsy. Two patients underwent the fourth
      biopsy, which revealed no prostate cancer. The patients with a positive biopsy
      had a significantly longer interval between the biopsies than the patients with a
      negative biopsy (P=0.0036). Furthermore, in both univariate and multivariate
      logistic regression analysis, only the interval between the biopsies proved to be
      an independent predictor of positive results at repeat biopsies (P=0.0094 and
      0.0019). CONCLUSIONS: Only the biopsy interval was a significant predictor of
      prostate cancer at repeat biopsies in both univariate and multivariate analysis.

PMID- 16643614
TI  - Five years experience of transrectal high-intensity focused ultrasound using the
      Sonablate device in the treatment of localized prostate cancer.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive
      technique used in achieve coagulation necrosis. We evaluated biochemical disease
      free survival rates, predictors of clinical outcome and morbidity in patients
      with localized prostate cancer treated with HIFU. METHODS: A total of 181
      consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery,
      Indianapolis, IN, USA). Biochemical recurrence was defined according to the
      criteria recommended by the American Society for Therapeutic Radiology and
      Oncology Consensus Panel. The median age and pretreatment prostate-specific
      antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39
      89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The
      median follow-up period for all patients was 18.0 months (range 4-68). RESULTS:
      The biochemical disease-free survival rates at 1, 3 and 5 years in all patients
      were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates
      at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0
      ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001).
      Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent
      predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy
      appears to be a safe and efficacious minimally invasive therapy for patients with
      localized prostate cancer, especially those with a pretreatment PSA level less
      than 20 ng/mL.

PMID- 16643615
TI  - Comparison of the effects of on-pump versus off-pump coronary artery bypass
      surgery on serum prostate-specific antigen levels.
AB  - AIM: To compare the effects of coronary artery bypass operation with or without
      extracorporeal circulation on serum total prostate-specific antigen levels.
      METHODS: Seventy-six men with a mean age of 57.04+/-9.27 years (range 44-77
      years), who underwent coronary artery bypass surgery were enrolled to the study.
      In 50 patients (Group I), coronary revascularization was performed using
      extracorporeal circulation, and in 26 patients (Group II) coronary bypass
      grafting was performed on the beating heart without using extracorporeal
      circulation. All the patients had serum total prostate-specific antigen levels
      measured preoperatively and twice postoperatively in the first and fifth
      postoperative days. Differences in mean total prostate-specific antigen levels
      between the two groups in the postoperative period were analysed. RESULTS: The
      mean preoperative total prostate-specific antigen levels in Group I and Group II
      were 1.28+/-1.13 ng/mL and 1.11+/-0.93 ng/mL, respectively, and there was no
      significant difference in the preoperative total prostate-specific antigen values
      between the two groups (P=0.519). In Group I, postoperative means were 4.96+/
      6.29 ng/mL and 5.86+/-9.09 ng/mL in the first and fifth days, respectively
      (P=0.0001, P=0.0001). Total prostate-specific antigen means in the same
      postoperative period for Group II were 2.13+/-2.72 ng/mL and 2.00+/-2.20 ng/mL,
      respectively (P=0.014, P=0.024). The comparison of total postoperative prostate
      specific antigen levels between the groups showed significantly higher elevation
      in Group I (postoperative day 1: P=0.013; day 5: P=0.05). CONCLUSIONS: Coronary
      revascularization can cause a statistically significant rise in serum total
      prostate-specific antigen levels. This rise is more marked in patients undergoing
      conventional coronary revascularization.

PMID- 16643616
TI  - Serum human glandular kallikrein 2 (hK2) for distinguishing stage and grade of
      prostate cancer.
AB  - BACKGROUND: Human glandular kallikrein (hK2) has been shown to add important
      information regarding the early detection and staging of prostate cancer.
      Preliminary analysis pointed out that hK2 may discriminate between pT2 and pT3
      tumors, and that hK2 may predict Gleason grade 4/5 cancer volume, better than
      prostate-specific antigen (PSA) or percent free PSA (%fPSA). We investigated the
      role of hK2 serum values for predicting pathological stage, grade and Gleason
      score. METHODS: Prostate-specific antigen, free PSA and hK2 were measured on 222
      untreated prostate cancer patients who had received radical prostatectomy at the
      Charite Hospital, Berlin, Germany. Pathological work up revealed pT2-cancer in
      111 patients and pT3-cancer in 111 patients. Grade 2 was found in 118 patients
      whereas grade 3 tumors were found in 104 patients. RESULTS: For pT2 and pT3
      patients, the %fPSA (P=0.006), the ratios hK2/fPSA (P=0.08) and hK2xtPSA/fPSA
      (P=0.002) were all significant different whereas hK2 (P=0.143) and PSA (P=0.1)
      did not differ. Between grade 2 and grade 3 tumors, the hK2 alone (P=0.27), the
      %fPSA (P=0.13), the ratios hK2/fPSA (P=0.94) and hK2xtPSA/fPSA (P=0.12) did not
      separate, whereas PSA (P=0.039) showed a difference. The same relationships were
      found between the two groups in Gleason score<7 and >or=7. Neither the hK2 ratio,
      nor % fPSA was different. CONCLUSION: Human glandular kallikrein was not
      different between pT2 and pT3, nor between G2 versus G3 or Gleason scores<7 and
      >or=7 prostate cancer. Together with %fPSA, hK2 may only help to distinguish
      preoperatively between pT2 and pT3 prostate cancer but cannot add further
      information.

PMID- 16643617
TI  - Outcome analysis for conservative management of Peyronie's disease.
AB  - BACKGROUND: We retrospectively analysed the outcomes of conservative management
      of Peyronie's disease and determined the factors predicting successful outcome.
      METHODS: The study involved 31 patients with Peyronie's disease who were treated
      at our institute between 1985 and 2003. We assessed the efficacy of vitamin E for
      the improvement of the symptoms, and the factors which contributed to successful
      outcome with conservative management using multivariate analysis. RESULTS: There
      was no statistically significant difference in the relief rate between the
      vitamin E and no-medication groups. The overall estimated relief rate was 67.5%
      at 2 years from presentation. The multivariate analysis revealed plaque size to
      be the only significant factor predicting the relief from all symptoms in
      patients with conservative management. The rate was 100% in patients having a
      plaque size of 20 mm or smaller and 20.0% in those having a size of larger than
      20 mm (P=0.005). CONCLUSIONS: We could not confirm the benefit of vitamin E for
      Peyronie's disease. Plaque size was the only significant factor predicting the
      relief from all symptoms. Patients with larger plaque might fail to respond to
      the conservative management.

PMID- 16643618
TI  - Robotic urological surgery in patients with prior abdominal operations is not
      associated with increased complications.
AB  - BACKGROUND: The da Vinci Surgical Robotic System is being increasingly used to
      perform complex urological operations by minimally invasive techniques. Prior
      abdominal surgery associated with intra-abdominal adhesions may complicate
      robotic surgery. METHODS: We used a cohort of consecutive 49 patients undergoing
      a variety of robotic urological procedures at our institution to study the impact
      of prior abdominal operations on early perioperative complications. RESULTS: A
      total of 21/49 (43%) patients (Group A) had no history of prior abdominal surgery
      and the rest 28/49 (57%; Group B) had undergone prior abdominal surgery. The
      incidence of peritoneal adhesions was significantly higher in patients with prior
      abdominal surgery compared to the rest of the cohort, 54% versus 10% (P=0.002).
      The median operative time, estimated blood loss, postoperative drop in
      hemoglobin, time to hospital discharge, postoperative narcotic analgesic use and
      postoperative complication rate between group A and group B were not
      statistically different. The overall perioperative complication rate for the
      entire cohort was 14.3%, with 6-8% of complications occurring in each of the two
      groups (P=1.0). Comparative subset analysis of 28 patients in Group B, 15 (54%)
      and 13 (46%) with or without intra-abdominal adhesions did not reveal a
      significant difference in perioperative complication rates either. However,
      operative time was longer in patients with intra-abdominal adhesions compared to
      patients without, median of 590 (281-922) and 434 (153-723) min respectively,
      although not statistically significant (P=0.059). CONCLUSION: Our study
      demonstrates that robotic urological surgery can be performed in patients with
      prior abdominal surgery without increased perioperative complications.

PMID- 16643619
TI  - Role of uric acid in different types of calcium oxalate renal calculi.
AB  - AIM: The presence of uric acid in the beginning zone of different types of 'pure'
      calcium oxalate renal calculi was evaluated with the aim of establishing the
      degree of participation of uric acid crystals in the formation of such calculi.
      METHODS: The core or fragment of different types of 'pure' calcium oxalate renal
      calculi was detached, pulverized and uric acid extracted. Uric acid was
      determined using a high-performance liquid chromatography/mass spectrometry
      method. RESULTS: In calcium oxalate monohydrate (COM) papillary calculi with a
      core constituted by COM crystals and organic matter, 0.030+/-0.007% uric acid was
      found in the core. In COM papillary calculi with a core constituted by
      hydroxyapatite, 0.031+/-0.008% uric acid was found in the core. In COM unattached
      calculi (formed in renal cavities) with the core mainly formed by COM crystals
      and organic matter, 0.24+/-0.09% uric acid was found in the core. In COM
      unattached calculi with the core formed by uric acid identifiable by scanning
      electron microscopy (SEM) coupled to X-ray microanalysis, 20.8+/-7.8% uric acid
      was found in the core. In calcium oxalate dihydrate (COD) unattached calculi
      containing little amounts of organic matter, 0.012+/-0.004% uric acid was found.
      In COD unattached calculi containing little amounts of organic matter and
      hydroxyapatite, 0.0030+/-0.0004% of uric acid was found. CONCLUSIONS: From these
      results it can be deduced that uric acid can play an important role as inducer
      (heterogeneous nucleant) of COM unattached calculi with the core formed by uric
      acid identifiable by SEM coupled to X-ray microanalysis (these calculi constitute
      the 1.2% of all calculi) and in COM unattached calculi with the core mainly
      formed by COM crystals and organic matter (these calculi constitute the 10.8% of
      all calculi).

PMID- 16643620
TI  - Significance of Fas expression alteration during tumor progression of renal cell
      carcinoma.
AB  - BACKGROUND: In order to characterize the alteration of apoptotic regulatory
      molecule expression during tumor progression of renal cell carcinoma (RCC), we
      compared the expression between tumor and normal tissues, and evaluated the
      relationship of the expression in tumors with pathological and clinical
      characteristics. METHODS: Competitive reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry (IHC) allowed the determination of Fas
      and bcl-2 mRNA and protein expression in surgically resected tumor and normal
      tissue of 50 RCC. RESULTS: The mRNA expression of Fas and bcl-2 in RCC was
      significantly reduced compared to that in normal tissues. An IHC analysis was
      supportive of the RT-PCR results. In terms of relationships with pathological and
      clinical characteristics, the mRNA and protein expression of Fas in high-stage or
      high-grade tumors was significantly higher than that in low-stage or low-grade
      tumors. Moreover, a statistically poor prognosis was observed in tumor cases
      expressing a high amount of mRNA. In bcl-2 analysis, the mRNA and protein
      expression was significantly reduced in clear cell tumors compared to chromophobe
      cell tumors. CONCLUSION: It is suggested that the reduced expression of Fas and
      bcl-2 in RCC compared with the expression in normal kidney is a prominent
      alteration of apoptotic regulatory molecules. The alteration of the up-regulated
      Fas expression might be characterized during the tumor progression stage. It is
      also suggested that the effect of alteration of bcl-2 expression might be minimal
      during the tumor progression stage because of the reduced expression in tumors of
      the clear cell type, which is the most dominant cell type in RCC.

PMID- 16643621
TI  - Peroxisome proliferator-activated receptor gamma is frequently underexpressed in
      renal cell carcinoma.
AB  - AIM: To examine peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA
      expression quantitatively in human renal cell carcinoma (RCC) cell lines and RCC
      tissue, as well as in corresponding normal kidney tissue. METHODS: We examined
      PPARgamma mRNA expression quantitatively in six human RCC cell lines by real-time
      reverse transcription-polymerase chain reaction. In addition, we evaluated the
      relationship between cell growth inhibition by PPARgamma ligands and the level of
      PPARgamma mRNA expression. We compared the expression of PPARgamma mRNA in 47 RCC
      tissues with that in corresponding normal kidney tissue, and investigated the
      relationship between clinicopathological features and the level of PPARgamma mRNA
      expression. RESULTS: Among the six RCC cell lines, five showed decreased
      PPARgamma mRNA expression. There was no relationship between the inhibitory
      effects of PPARgamma ligands and PPARgamma mRNA expression levels. Of the tissues
      from 47 RCC patients, 25 (53%) showed decreased expression of PPARgamma mRNA
      compared to corresponding normal kidney tissue, and one was equivalent to normal
      tissue. These patients had distant metastasis at diagnosis more frequently than
      the remaining patients with high expression. There was also a trend for these
      patients to have a higher stage. CONCLUSIONS: Most RCC cell lines showed
      decreased expression of PPARgamma mRNA. However, the level of PPARgamma mRNA
      expression did not affect cell growth inhibition by PPARgamma ligands. More than
      half of the tissues from RCC patients had low expression of PPARgamma mRNA, and
      such carcinomas might have more aggressive behavior.

PMID- 16643622
TI  - Prostaglandin E2 release from isolated bladder strips in rats with spinal cord
      injury.
AB  - AIM: Recent studies have shown that various factors contribute to the increased
      excitability into the bladder afferent nerves in spinal cord injury (SCI) rats.
      It has been reported that prostaglandins (PG) act as local modulators of reflex
      micturition in pathological conditions. In the present study, we measured the
      amount of PGE2 release from the bladder of chronic SCI rats. METHODS: Spinal cord
      was transected at the level of T8-9 in adult female Sprague-Dawley rats. After 10
      weeks, specimens of the urinary bladder were obtained from SCI rats and sham
      injured control rats, and bladder strips were dissected from the bladder. Using
      an muscle-bath technique and a microdialysis procedure, the dialysate, containing
      substance released from bladder strips, was collected. Then the amount of PGE2 in
      the dialysate was measured by radioimmunoassay. RESULTS: Excretion of urinary
      PGE2 was significantly higher in SCI rats than in control rats. PGE2 release from
      bladder strips was significantly higher in SCI rats than in control rats. Removal
      of urothelium caused significant decreases in PGE2 release in both control and
      SCI rats. Stretches of the bladder strips caused significant resting tension
      dependent increases in PGE2 release from the strips with urothelium. CONCLUSIONS:
      The present data suggest that bladder urothelium partly contributes to the
      increase in PGE2 release from the bladder, and that bladder distension may cause
      increases in PGE2 release in SCI rats.

PMID- 16643623
TI  - Rapid detection of the fluoroquinolone resistance-associated ParC mutation in
      Neisseria gonorrhoeae using TaqMan probes.
AB  - BACKGROUND: In fluoroquinolone-resistant Neisseria gonorrhoeae, the amino acid
      mutations in the fluoroquinolone-resistant determining region (QRDR) of the parC
      gene are an important factor. The aim of the present study was to develop a rapid
      detection method of a serine 88 to proline substitution in parC which we
      previously showed as having significantly higher fluoroquinolone minimal
      inhibitory concentrations (MIC) using the TaqMan discrimination system. METHODS:
      We extracted DNA from 90 urine or urethral swab samples obtained from male
      patients with urethritis caused by N. gonorrhoeae. After DNA extraction, they
      were subjected to real-time polymerase chain reaction (PCR) using a TaqMan
      discrimination system and compared with the results of conventional DNA
      sequencing. RESULTS: Of the 90 samples, the TaqMan technique result showed 13
      samples that were classified as having a serine 88 to proline mutation in parC,
      and 77 samples that did not have a serine 88 to proline mutation in parC. The
      classifications of all samples completely corresponded to those determined by
      conventional DNA sequencing. We also found that N. gonorrhoeae with a serine 88
      to proline mutation in parC have a significantly higher MIC to ciprofloxacin than
      that without a serine 88 to proline mutant in parC. CONCLUSIONS: The present
      genotyping method of real-time PCR using a TaqMan discrimination system could be
      applied to the rapid detection of a serine 88 to proline amino acid mutation in
      parC of N. gonorrhoeae. This point mutation is significant for the determination
      of fluoruquinolone resistance. This rapid detection system may lead to the
      prevention of use of noneffective antimicrobial agents and a decrease of
      resistant strains.

PMID- 16643624
TI  - Interferon-related mental deterioration after craniotomy for removal of
      metastatic renal cancer.
AB  - Interferon-related severe adverse events on the central nervous system are
      relatively rare, because interferon-alpha (INF-alpha) can not cross an intact
      blood-brain barrier. We experienced remarkable mental deterioration caused by INF
      alpha administration in a 43-year-old man with renal cell carcinoma after
      surgical removal of a metastatic brain tumor. We detected a high concentration of
      INF-alpha in a cerebrospinal fluid sample, which was comparable to that in the
      serum at 24 h after the administration of INF-alpha; 5x10(6) IU i.m., suggesting
      that the blood-brain barrier was damaged somehow by the craniotomy. The mental
      deterioration improved shortly after discontinuation of the INF-alpha
      administration.

PMID- 16643625
TI  - Extraskeletal mesenchymal chondrosarcoma of the kidney.
AB  - A 61-year-old woman was referred for evaluation of an incidental mass found on
      the right kidney. Abdominal ultrasonography and computed tomography showed a 3-cm
      tumor with calcification and peripheral enhancement. Under the diagnosis of renal
      cell carcinoma, a transabdominal right radical nephrectomy was performed. The
      pathological diagnosis was extraskeletal mesenchymal chondrosarcoma of the
      kidney. No recurrence or metastasis occurred during a 6-year follow up. Primary
      renal chondrosarcoma is extremely rare, this being only the fifth case reported
      in the English literature, and the patient's extended survival is attributed to
      the small size of the tumor, as well as early diagnosis and treatment.

PMID- 16643626
TI  - Laparoscopic management of a transitional cell carcinoma arising in a right
      ectopic ureter.
AB  - Ectopic ureter is a rare abnormality, so presenting a transitional cell carcinoma
      (TCC) arising from an ectopic ureter is extremely rare. We report here a case of
      a man with an invasive transitional cell carcinoma arising from a right ectopic
      ureter and managed by laparoscopy. To our knowledge, this is the fourth case
      described in the literature, and the second case of a TCC arising in a right
      ectopic ureter.

PMID- 16643627
TI  - Uncommon complication of endoscopic ureterolithotripsy: the stone granuloma.
AB  - Endoscopic management of urolithiasis is one of the commonest urological
      procedures today. It is usually safe and effective but one of the possible
      complications is ureteral obstruction. Stone fragmentation after ballistic
      lithotripsy and ureteral wall perforation could explain the mechanism responsible
      for this occurrence. We report a case of stone granuloma, occurring after a
      ballistic ureterolithotripsy.

PMID- 16643628
TI  - Combined surgical intervention and medical management in a case of atypical
      idiopathic retroperitoneal fibrosis.
AB  - Idiopathic retroperitoneal fibrosis (RPF) is one of the causes of obstructive
      uropathy. This disease, ever since its original description in 1948, has
      undergone much trial and error in its management. We present a case of a rare
      type of idiopathic RPF causing obstructive uropathy, which is perirenal and
      different from the classical RPF seen around the great vessels. To our knowledge,
      such a type of RPF has not been described. We treated the patient by a combined
      surgical approach in the form of ureterolysis and omentoplasty, followed by
      medical management with steroids and tamoxifen. The combined regimen yielded
      excellent results, and the patient is doing well at 9 months of follow up. The
      rarity of the presentation, with predominant bilateral perirenal fibrosis, and
      response of perirenal RPF to steroids and tamoxifen, is highlighted in this case
      presentation.

PMID- 16643629
TI  - Transient anuria requiring nephrostomy after intravesical bacillus Calmette
      Guerin instillations for superficial bladder cancer.
AB  - A 76-year-old man received intravesical bacillus Calmette-Guerin (BCG)
      instillations for recurrent superficial bladder cancer. He had undergone right
      nephroureterectomy for right renal pelvic cancer 9 months previously. He
      presented with anuria and left hydronephrosis after the fourth instillation, with
      serum creatinine increasing up to 15.7 mg/dL. Percutaneous nephrostomy was
      indwelled, and antegrade pyelography showed left vesicoureteral obstruction.
      There was no sign of recurrent bladder cancer or ureteral cancer. He started
      spontaneous voiding on day 4 and the nephrostomy was removed on day 8. Most of
      the side-effects of intravesical BCG therapy are minor, and major adverse
      reactions are rare. Life-threatening ureteral obstruction would be a rare
      complication of BCG immunotherapy. Although BCG intravesical instillation after
      nephroureterectomy is a common practice, special care should be taken of renal
      function in patients with unilateral kidney during BCG therapy.

PMID- 16643630
TI  - Concurrent diagnosis of urothelial carcinoma and squamous cell carcinoma of the
      bladder in a patient with a vesicorectal fistula from invasive rectal cancer.
AB  - A 47-year-old man underwent a low anterior resection of the rectosigmoid colon
      with en bloc cystoprostatectomy for vesicorectal fistula due to a locally
      advanced rectal cancer. Histopathological examination of the bladder revealed two
      additional primary malignancies: urothelial carcinoma and squamous cell
      carcinoma. To our knowledge, this is the first reported case of two
      histologically distinct urothelial malignancies that were diagnosed during a work
      up of vesicorectal fistula due to adenocarcinoma of the rectum.

PMID- 16643631
TI  - Paraffinoma of the urinary bladder.
AB  - We present a rare case of paraffinoma of the urinary bladder. Paraffinomas
      involving the urinary tract are rare and not well described. They are usually
      associated with insertion of materials into the lower urinary tract by patients
      with psychiatric disorders. Not only can the diagnosis be delayed, but they are
      also easily misdiagnosed. They are usually discovered during work up for
      recurrent urinary tract infections. Therefore, a high index of suspicion is
      needed in patients with recurrent urinary tract infections, psychiatric
      histories, and past history of foreign object insertion. Treatment options for
      paraffinoma includes open surgical excision, possibly transurethral excision or
      dissolution, and is usually dictated by the size of the mass.

PMID- 16643632
TI  - Intravesical migration of intrauterine device resulting in pregnancy.
AB  - Spontaneous migration of an intrauterine device into the bladder is very rare. A
      29-year-old woman in whom an intrauterine device had been placed 6 years
      previously, presented complaining of chronic pelvic pain and recurrent irritative
      urinary tract symptoms. One year after insertion she had became pregnant and
      given birth without complications. Intravesical migration of the intrauterine
      device was confirmed by sonography and cystoscopy. The intrauterine device was
      removed by suprapubic cystostomy.

PMID- 16643633
TI  - Discovery of a pituitary adenoma following a gonadotropin-releasing hormone
      agonist in a patient with prostate cancer.
AB  - Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of
      choice for locally advanced and metastatic prostate cancer. We report a case of
      prostate cancer in which this treatment led to severe symptoms of intracranial
      hypertension due to the concomitant presence of an asymptomatic functional
      pituitary adenoma. A 70-year-old white man was initially evaluated for a
      multifocal adenocarcinoma, Gleason score 6 (3+3) with perineural invasion
      suggesting an extracapsular extension. A conformational external beam radiation
      (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10
      days after the administration of leuprolide the patient complained of visual
      disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic
      resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To
      relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was
      necessary. The histopathological examination revealed an invasive gonadotroph
      pituitary adenoma. Two years later, there is no sign of progression either on his
      prostatic disease (prostate-specific antigen of 0.21 ng/mL) or on his pituitary
      disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with
      values of the hypothalamic-pituitary axis in the normal range. We advocate that a
      high index of suspicion of pituitary tumor must be considered in any case of
      intracranial hypertension following the administration of GnRH agonist. Abarelix
      could have a place in such cases.

PMID- 16643634
TI  - Primary immature teratoma of the prostate with angiosarcoma component: its
      unusual response to chemotherapy.
AB  - Here, we present a case of immature teratoma of prostatic origin, which included
      an angiosarcoma component. This mass proved unresponsive against preoperative
      chemotherapy for immature teratoma. Angiosarcoma, although quite rare, should be
      included in the differential diagnosis as a component of prostatic teratoma,
      especially in cases in which the tumor proves unresponsive to well-known
      chemotherapeutic protocols. This is, to our knowledge, the first reported case of
      primary prostatic immature teratoma containing an angiosarcoma component.

PMID- 16643635
TI  - Hydatid cyst of the seminal vesicle.
AB  - We present a rare case of a hydatid cyst involving the seminal vesicle of a 48
      year-old man. Urinary retention was the initial symptom. Both imaging and
      clinical evaluation revealed a substantial retrovesical cystic mass. The
      histopathological report was 'hydatid cyst of the seminal vesicle'.

PMID- 16643636
TI  - Laparoscopic excision of seminal vesicle cyst revealed by obstruction urinary
      symptoms.
AB  - Primary diseases of the seminal vesicle are rare. Most seminal vesicle cysts are
      congenital, and two-thirds are associated with renal dysplasia or agenesis and
      ectopic ureter opening into the seminal vesicle. Acquired cysts may be due to
      genitourinary infections, surgical prostate resection or ejaculatory duct
      lithiasis. We report a case of video laparoscopic ablation of seminal vesicle
      cysts.

PMID- 16643637
TI  - Ureteral obstruction associated with pelvic inflammatory disease in a long-term
      intrauterine contraceptive device user.
AB  - We report herein a case of ureteral obstruction associated with pelvic
      inflammatory disease in a long-term intrauterine contraceptive device (IUD) user.
      A 62-year-old woman presented with a 2-week history of left flank pain and high
      fever, but no abdominal pain. She had forgotten the use of an IUD. Retrograde
      pyelography showed a stricture in the lower third of the left ureter. Magnetic
      resonance showed swelling of the uterus wall and left parametria, but did not
      reveal the presence of an IUD. Subtotal hysterectomy, bilateral salpingo
      oophorectomy and left nephronureterectomy was performed. The IUD was then found
      in the uterine cavity. The results of pathological and bacteriological findings
      for Actinomyces infection were negative. Therefore we diagnosed this case as
      ureteral obstruction associated with pelvic inflammatory disease. Ureteral
      obstruction associated with pelvic inflammatory disease in a long-term IUD user
      is extremely rare.

PMID- 16643638
TI  - Penile Kaposi's sarcomas in a circumcised and HIV-seronegative patient.
AB  - Kaposi's sarcoma (KS) limited to penis is rare and usually observed in AIDS
      patients. However, in circumcised and HIV-seronegative patients, KS confined to
      the penis is extremely rare. We present the case of an HIV-seronegative and
      circumcised 55-year-old man, who presented with two reddish papules, one 5 mm in
      diameter on the coronal sulcus near the frenulum, and the other 2 mm in diameter
      on the glans penis, which were reported as a Kaposi's sarcoma after excision of
      the lesion.

PMID- 16643639
TI  - Treatment of adult female epispadias without exstrophy in the presence of
      rhabdosphincter function.
AB  - Female epispadias without exstrophy is a very rare entity. Symptoms of female
      epispadias are primary urinary incontinence and anatomical abnormal features. A
      24-year-old married women with two children presented with primary urinary
      incontinence. Due to previous failure of correct diagnosis and ineffective
      medical treatment, the patient developed psychological problems (anxiety and
      depression). In the presence of minimal rhabdosphincter function we could achieve
      socially acceptable urinary continence by bladder neck plication and a Burch
      colposuspension. The patient did not consent to a major reconstruction.

PMID- 16643640
TI  - Osteosarcoma of the testis.
AB  - This report describes a case of primary osteosarcoma of the testis in a 60-year
      old man. Treatment consisted of an inguinal orchiectomy with no adjuvant therapy.
      The patient is alive and doing well without recurrent disease at 18 months after
      diagnosis. Only three reports have been published on primary osteosarcoma of the
      testis. The origin of this tumor from undifferentiated mesenchymal cells or from
      a malignant transformation of pre-existing teratomatous elements is still
      unclear. Management guidelines are difficult to establish due to the rarity of
      such tumors, but inguinal orchiectomy with careful follow up appears to be
      sufficient treatment.

PMID- 16643641
TI  - Usefulness of contrast-enhanced ultrasound for the diagnosis of recurrent renal
      cell carcinoma in contralateral kidney.
AB  - We studied contrast-enhanced ultrasound (CEU) for recurrence of renal cell
      carcinoma (RCC) at the contralateral kidney during postoperative follow up of
      localized renal cell carcinoma. CEU successfully detected all recurring cases,
      despite the fact that 5/6 cases were observed using conventional ultrasound; the
      remaining one case was not detected using conventional ultrasound. CEU using
      Levovisto successfully revealed renal tumors as RCC. Lesions were diagnosed as
      cystic renal tumors by Bosniac classification, and pathological findings
      demonstrated RCC, in accordance with the prior tumor.

PMID- 16643642
TI  - Influence of the blood bacterial load on the meningeal inflammatory response in
      Streptococcus pneumoniae meningitis.
AB  - BACKGROUND: Despite bacteraemia is present in the majority of patients with
      pneumococcal, little is known about the influence of the systemic infection on
      the meningeal inflammatory response. METHODS: To explore the role of systemic
      infection on the meningeal inflammation, experimental meningitis was induced by
      intracisternal injection of approximately 1 x 10(6) CFU Streptococcus pneumoniae,
      type 3, and the 26 rabbits were either provided with approximately 1 x 10(6) CFU
      S. pneumoniae intravenously at 0 hour ("bacteraemic" rabbits, n = 9), immunized
      with paraformaldehyde-killed S. pneumoniae for 5 weeks prior to the experiment
      ("immunized" rabbits", n = 8), or not treated further ("control" rabbits, n = 9).
      WBC and bacterial concentrations were determined in CSF and blood every second
      hour during a 16 hours study period together with CSF IL-8 and protein levels. We
      also studied CSF and blood WBC levels in 153 pneumococcal meningitis patients
      with and without presence of bacteraemia. RESULTS: As designed, blood bacterial
      concentrations were significantly different among three experimental groups
      during the 16 hours study period (Kruskal Wallis test, P < 0.05), whereas no
      differences in CSF bacterial levels were observed (P > 0.05). Blood WBC decreased
      in bacteraemic rabbits between approximately 10-16 hours after the bacterial
      inoculation in contrast to an increase for both the immunized rabbits and
      controls (P < 0.05). The CSF pleocytosis was attenuated in bacteraemic rabbits as
      compared to the two other groups between 12-16 hours from time of infection (P <
      0.017), despite accelerated CSF IL-8 levels in bacteraemic rabbits. In patients
      with pneumococcal meningitis, no significant difference in CSF WBC was observed
      between patients with or without bacteraemia at admission (n = 103, 1740
      cells/microL (123-4032) vs. n = 50, 1961 cells/microL (673-5182), respectively, P
      = 0.18), but there was a significant correlation between CSF and blood WBC (n =
      127, Spearman rho = 0.234, P = 0.008). CONCLUSION: Our results suggest that a
      decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal
      meningitis results in an attenuated CSF pleocytosis.

PMID- 16643643
TI  - Knowledge of modifiable risk factors of heart disease among patients with acute
      myocardial infarction in Karachi, Pakistan: a cross sectional study.
AB  - BACKGROUND: Knowledge is an important pre-requisite for implementing both primary
      as well as secondary preventive strategies for cardiovascular disease (CVD).
      There are no estimates of the level of knowledge of risk factor of heart disease
      in patients with CVD. We estimated the level of knowledge of modifiable risk
      factors and determined the factors associated with good level of knowledge among
      patients presenting with their first acute myocardial infarction (AMI) in a
      tertiary care hospital in Karachi, Pakistan. METHODS: A hospital based cross
      sectional study was conducted at the National Institute of Cardiovascular
      Disease, a major tertiary care hospital in Karachi Pakistan. Patients admitted
      with their first AMI were eligible to participate. Standard questionnaire was
      used to interview 720 subjects. Knowledge of four modifiable risk factors of
      heart disease: fatty food consumption, smoking, obesity and exercise were
      assessed. The participants knowing three out of four risk factors were regarded
      as having a good level of knowledge. A multiple logistic regression model was
      constructed to identify the determinants of good level of knowledge. RESULTS: The
      mean age (SD) was 54 (11.66) years. A mere 42% of our study population had a good
      level of knowledge. In multiple logistic regression analysis, independent
      predictors of "good" level of knowledge were (odds ratio [95% confidence
      interval]) more than ten years of schooling were 2.5 [1.30, 4.80] (verses no
      schooling at all) and nuclear family system (verses extended family system) 2.54
      [1.65, 3.89]. In addition, Sindhi ethnicity OR [3.03], higher level of exercise
      OR [2.76] and non user of tobacco OR [2.53] were also predictors of good level of
      knowledge. CONCLUSION: Our findings highlight the lack of good level of knowledge
      of modifiable risk factors for heart disease among subjects admitted with AMI in
      Pakistan. There is urgent need for aggressive and targeted educational strategies
      in the Pakistani population.

PMID- 16643644
TI  - GNU polyxmass: a software framework for mass spectrometric simulations of linear
      (bio-)polymeric analytes.
AB  - BACKGROUND: Nowadays, a variety of (bio-)polymers can be analyzed by mass
      spectrometry. The detailed interpretation of the spectra requires a huge number
      of "hypothesis cycles", comprising the following three actions 1) put forth a
      structural hypothesis, 2) test it, 3) (in)validate it. This time-consuming and
      painstaking data scrutiny is alleviated by using specialized software tools.
      However, all the software tools available to date are polymer chemistry-specific.
      This imposes a heavy overhead to researchers who do mass spectrometry on a
      variety of (bio-)polymers, as each polymer type will require a different software
      tool to perform data simulations and analyses. We developed a software to address
      the lack of an integrated software framework able to deal with different polymer
      chemistries. RESULTS: The GNU polyxmass software framework performs common (bio
      )chemical simulations-along with simultaneous mass spectrometric calculations-for
      any kind of linear bio-polymeric analyte (DNA, RNA, saccharides or proteins). The
      framework is organized into three modules, all accessible from one single binary
      program. The modules let the user to 1) define brand new polymer chemistries, 2)
      perform quick mass calculations using a desktop calculator paradigm, 3)
      graphically edit polymer sequences and perform (bio-)chemical/mass spectrometric
      simulations. Any aspect of the mass calculations, polymer chemistry reactions or
      graphical polymer sequence editing is configurable. CONCLUSION: The scientist who
      uses mass spectrometry to characterize (bio-)polymeric analytes of different
      chemistries is provided with a single software framework for his data
      prediction/analysis needs, whatever the polymer chemistry being involved.

PMID- 16643645
TI  - Transcriptional profiling of mesenchymal stromal cells from young and old rats in
      response to Dexamethasone.
AB  - BACKGROUND: Marrow-derived stromal cells (MSCs) maintain the capability of self
      renewal and differentiation into multiple lineages in adult life. Age-related
      changes are recognized by a decline in the stemness potential that result in
      reduced regeneration potential of the skeleton. To explore the molecular events
      that underline skeletal physiology during aging we catalogued the profile of gene
      expression in ex vivo cultured MSCs derived from 3 and 15 month old rats. The ex
      vivo cultured cells were analyzed following challenge with or without
      Dexamethasone (Dex). RNA retrieved from these cells was analyzed using Affymetrix
      Gene Chips to compare the effect of Dex on gene expression in both age groups.
      RESULTS: The molecular mechanisms that underline skeletal senescence were studied
      by gene expression analysis of RNA harvested from MSCs. The analysis resulted in
      complex profiles of gene expression of various differentiation pathways. We
      revealed changes of lineage-specific gene expression; in general the pattern of
      expression included repression of proliferation and induction of differentiation.
      The functional analysis of genes clustered were related to major pathways; an
      increase in bone remodeling, osteogenesis and muscle formation, coupled with a
      decrease in adipogenesis. We demonstrated a Dex-related decrease in immune
      response and in genes that regulate bone resorption and an increase in
      osteoblastic differentiation. Myogenic-related genes and genes that regulate cell
      cycle were induced by Dex. While Dex repressed genes related to adipogenesis and
      catabolism, this decrease was complementary to an increase in expression of genes
      related to osteogenesis. CONCLUSION: This study summarizes the genes expressed in
      the ex vivo cultured mesenchymal cells and their response to Dex. Functional
      clustering highlights the complexity of gene expression in MSCs and will advance
      the understanding of major pathways that trigger the natural changes underlining
      physiological aging. The high throughput analysis shed light on the anabolic
      effect of Dex and the relationship between osteogenesis, myogenesis and
      adipogenesis in the bone marrow cells.

PMID- 16643646
TI  - The prolongation of somatic support in a pregnant woman with brain-death: a case
      report.
AB  - BACKGROUND: Medical literature has increasingly reported cases of maternal brain
      death during pregnancy. This is a rare situation which demands the decision and,
      depending on the gestational age, the implementation of a set of measures to
      prolong the homeostasis of the human body after brain death for the purpose of
      maintaining the foetus alive until its viability. CASE PRESENTATION: A 40 year
      old woman suffered an intracranial haemorrhage during the 25th week of pregnancy.
      Despite neurosurgical drainage of a gross intraparenchymatous haematoma, the
      patient developed brain death. Upon confirmation of this diagnosis, she received
      full ventilatory and nutritional support, vasoactive drugs, maintenance of
      normothermia, hormone replacement and other supportive measures required to
      prolong gestation and improve the survival prognosis of her foetus. All decisions
      regarding the patient's treatment were taken in consensus with her family. She
      also received corticosteroids to accelerate foetal lung maturity. During the
      twenty-five days of somatic support, the woman's condition remained stable;
      however, during the last seven days the foetus developed oligohydramnios and
      brain-sparring, which led the medical team to take the decision to perform a
      Caesarean section at that moment. After delivery, the patient's organs were
      removed for donation. The male infant was born weighing 815 g, with an Apgar
      score of 9 and 10 at the first and fifth minutes, respectively. The infant was
      admitted to the neonatal intensive care unit, but did not require mechanical
      ventilation and had no major complications. He was discharged at 40 days of life,
      with no sequelae and weighing 1850 g. CONCLUSION: These results are in accordance
      with findings from previous studies and case reports suggesting the
      appropriateness and safety of extended somatic support during pregnancy under
      certain circumstances. They also suggest the need for prompt diagnosis of brain
      death before the occurrence of physiological degeneration, rapid evaluation of
      foetal status and the decision of the family together with the medical team to
      prolong maternal somatic support. The occurrence of maternal brain death is a
      tragedy, but it may also represent a challenging opportunity to save the life of
      the foetus and, in addition, permit donation of the maternal organs.

PMID- 16643647
TI  - Selection of a set of reliable reference genes for quantitative real-time PCR in
      normal equine skin and in equine sarcoids.
AB  - BACKGROUND: Real-time quantitative PCR can be a very powerful and accurate
      technique to examine gene transcription patterns in different biological
      conditions. One of the critical steps in comparing transcription profiles is
      accurate normalisation. In most of the studies published on real-time PCR in
      horses, normalisation occurred against only one reference gene, usually GAPDH or
      ACTB, without validation of its expression stability. This might result in
      unreliable conclusions, because it has been demonstrated that the expression
      levels of so called "housekeeping genes" may vary considerably in different
      tissues, cell types or disease stages, particularly in clinical samples
      associated with malignant disease. The goal of this study was to establish a
      reliable set of reference genes for studies concerning normal equine skin and
      equine sarcoids, which are the most common skin tumour in horses. RESULTS: In the
      present study the gene transcription levels of 6 commonly used reference genes
      (ACTB, B2M, HPRT1, UBB, TUBA1 and RPL32) were determined in normal equine skin
      and in equine sarcoids. After applying the geNorm applet to this set of genes,
      TUBA1, ACTB and UBB were found to be most stable in normal skin and B2M, ACTB and
      UBB in equine sarcoids. CONCLUSION: Based on these results, TUBA1, ACTB and UBB,
      respectively B2M, ACTB and UBB can be proposed as reference gene panels for
      accurate normalisation of quantitative data for normal equine skin, respectively
      equine sarcoids. When normal skin and equine sarcoids are compared, the use of
      the geometric mean of UBB, ACTB and B2M can be recommended as a reliable and
      accurate normalisation factor.

PMID- 16643648
TI  - MIDAS: software for analysis and visualisation of interallelic disequilibrium
      between multiallelic markers.
AB  - BACKGROUND: Various software tools are available for the display of pairwise
      linkage disequilibrium across multiple single nucleotide polymorphisms. The
      HapMap project also presents these graphics within their website. However, these
      approaches are limited in their use of data from multiallelic markers and provide
      limited information in a graphical form. RESULTS: We have developed a software
      package (MIDAS - Multiallelic Interallelic Disequilibrium Analysis Software) for
      the estimation and graphical display of interallelic linkage disequilibrium.
      Linkage disequilibrium is analysed for each allelic combination (of one allele
      from each of two loci), between all pairwise combinations of any type of
      multiallelic loci in a contig (or any set) of many loci (including single
      nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data
      are presented graphically in a novel and informative way, and can also be
      exported in tabular form for other analyses. This approach facilitates
      visualisation of patterns of linkage disequilibrium across genomic regions,
      analysis of the relationships between different alleles of multiallelic markers
      and inferences about patterns of evolution and selection. CONCLUSION: MIDAS is a
      linkage disequilibrium analysis program with a comprehensive graphical user
      interface providing novel views of patterns of linkage disequilibrium between all
      types of multiallelic and biallelic markers.

PMID- 16643649
TI  - Bovine CD2-/NKp46+ cells are fully functional natural killer cells with a high
      activation status.
AB  - BACKGROUND: Natural killer (NK) cells in the cow have been elusive due to the
      lack of specific NK cell markers, and various criteria including a CD3-/CD2+
      phenotype have been used to identify such cells. The recent characterization of
      the NK-specific NKp46 receptor has allowed a more precise definition of bovine NK
      cells. NK cells are known as a heterogeneous cell group, and we here report the
      first functional study of bovine NK cell subsets, based on the expression of CD2.
      RESULTS: Bovine CD2- NK cells, a minor subset in blood, proliferated more rapidly
      in the presence of IL-2, dominating the cultures after a few days. Grown
      separately with IL-2, CD2- and CD2+ NK cell subsets did not change CD2 expression
      for at least two weeks. In blood, CD2- NK cells showed a higher expression of
      CD44 and CD25, consistent with a high activation status. A higher proportion of
      CD2- NK cells had intracellular interferon-gamma in the cytoplasm in response to
      IL-2 and IL-12 stimulation, and the CD2- subset secreted more interferon-gamma
      when cultured separately. Cytotoxic capacity was similar in both subsets, and
      both carried transcripts for the NK cell receptors KIR, CD16, CD94 and KLRJ.
      Ligation by one out of two tested anti-CD2 monoclonal antibodies could trigger
      interferon-gamma production from NK cells, but neither of them could alter
      cytotoxicity. CONCLUSION: These results provide evidence that bovine CD2- as well
      as CD2+ cells of the NKp46+ phenotype are fully functional NK cells, the CD2-
      subset showing signs of being more activated in the circulation.

PMID- 16643650
TI  - Optimization and evaluation of surface-enhanced laser-desorption/ionization time
      of-flight mass spectrometry for protein profiling of cerebrospinal fluid.
AB  - Cerebrospinal fluid (CSF) potentially carries an archive of peptides and small
      proteins relevant to pathological processes in the central nervous system (CNS)
      and surrounding brain tissue. Proteomics is especially well suited for the
      discovery of biomarkers of diagnostic potential in CSF for early diagnosis and
      discrimination of several neurodegenerative diseases. ProteinChip surface
      enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF
      MS) is one such approach which offers a unique platform for high throughput
      profiling of peptides and small proteins in CSF. In this study, we evaluated
      methodologies for the retention of CSF proteins < 20 kDa in size, and identify a
      strategy for screening small proteins and peptides in CSF. ProteinChip array
      types, along with sample and binding buffer conditions, and matrices were
      investigated. By coupling the processing of arrays to a liquid handler
      reproducible and reliable profiles, with mean peak coefficients of variation <
      20%, were achieved for intra- and inter-assays under selected conditions. Based
      on peak m/z we found a high degree of overlap between the tested array surfaces.
      The combination of CM10 and IMAC30 arrays was sufficient to represent between 80
      90% of all assigned peaks when using either sinapinic acid or alpha-Cyano-4
      hydroxycinnamic acid as the energy absorbing matrices. Moreover, arrays processed
      with SPA consistently showed better peak resolution and higher peak number across
      all surfaces within the measured mass range. We intend to use CM10 and IMAC30
      arrays prepared in sinapinic acid as a fast and cost-effective approach to drive
      decisions on sample selection prior to more in-depth discovery of diagnostic
      biomarkers in CSF using alternative but complementary proteomic strategies.

PMID- 16643651
TI  - Neuroactive substances specifically modulate rhythmic body contractions in the
      nerveless metazoon Tethya wilhelma (Demospongiae, Porifera).
AB  - BACKGROUND: Sponges (Porifera) are nerve- and muscleless metazoa, but display
      coordinated motor reactions. Therefore, they represent a valuable phylum to
      investigate coordination systems, which evolved in a hypothetical Urmetazoon
      prior to the central nervous system (CNS) of later metazoa. We have chosen the
      contractile and locomotive species Tethya wilhelma (Demospongiae, Hadromerida) as
      a model system for our research, using quantitative analysis based on digital
      time lapse imaging. In order to evaluate candidate coordination pathways, we
      extracorporeally tested a number of chemical messengers, agonists and antagonists
      known from chemical signalling pathways in animals with CNS. RESULTS: Sponge body
      contraction of T. wilhelma was induced by caffeine, glycine, serotonine, nitric
      oxide (NO) and extracellular cyclic adenosine monophosphate (cAMP). The induction
      by glycine and cAMP followed patterns varying from other substances. Induction by
      cAMP was delayed, while glycine lead to a bi-phasic contraction response. The
      frequency of the endogenous contraction rhythm of T. wilhelma was significantly
      decreased by adrenaline and NO, with the same tendency for cAMP and
      acetylcholine. In contrast, caffeine and glycine increased the contraction
      frequency. The endogenous rhythm appeared irregular during application of
      caffeine, adrenaline, NO and cAMP. Caffeine, glycine and NO attenuated the
      contraction amplitude. All effects on the endogenous rhythm were neutralised by
      the washout of the substances from the experimental reactor system. CONCLUSION:
      Our study demonstrates that a number of chemical messengers, agonists and
      antagonists induce contraction and/or modulate the endogenous contraction rhythm
      and amplitude of our nerveless model metazoon T. wilhelma. We conclude that a
      relatively complex system of chemical messengers regulates the contraction
      behaviour through auto- and paracrine signalling, which is presented in a
      hypothetical model. We assume that adrenergic, adenosynergic and glycinergic
      pathways, as well as pathways based on NO and extracellular cAMP are candidates
      for the regulation and timing of the endogenous contraction rhythm within
      pacemaker cells, while GABA, glutamate and serotonine are candidates for the
      direct coordination of the contractile cells.

PMID- 16643652
TI  - Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.
AB  - BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads
      to hypercortisolism. Here, we report the first case of Cushing' syndrome caused
      by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover,
      diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors
      are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented
      with clinical features and biochemical tests suggestive of ectopic Cushing's
      syndrome. First, subtotal thyroidectomy was performed without remission of
      hypercortisolism, because an octreotide scan showed increased activity in the
      left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one
      of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion
      of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the
      pituitary lesion within the posterior lobe did not improve hypercortisolism and
      we continued to treat the patient with metyrapone to block cortisol production.
      At 18-months follow-up from initial presentation, we detected an ACTH-producing
      neuroendocrine carcinoma of the mesentery by using a combination of octreotide
      scan, computed tomography scan, and positron emission tomography.
      Intraoperatively, use of a gamma probe after administration of radiolabeled
      (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After
      removal of this carcinoma, the patient improved clinically. Laboratory testing
      confirmed remission of hypercortisolism. An octreotide scan 7 months after
      surgery showed normal results. CONCLUSION: This case underscores the diagnostic
      challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of
      cells, in this case of mesenteric cells that can start producing and secreting
      ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This
      case also suggests that patients with ectopic Cushing's syndrome and an
      octreotide scan positive in atypical locations may benefit from explorative
      radioguided surgery using (111)In-pentetreotide and a gamma probe.

PMID- 16643653
TI  - The silent HIV epidemic among pregnant women within rural Northern Tanzania.
AB  - BACKGROUND: Many national antenatal clinics (ANC) based HIV surveillance systems
      in sub-Saharan Africa have limited coverage of remote rural sites, a weakness
      that compromises adequate estimation, monitoring and development of effective
      preventive and care programmes. To address this void in rural Manyara and Singida
      within Northern Tanzania, we conducted antenatal clinic-based sentinel
      surveillance. METHODS: We consecutively enrolled 1377 counselled and consenting
      pregnant women attending ANC clinics for the first time during the current
      pregnancy. The study was conducted in six antenatal clinics, within three
      divisions of rural Manyara and Singida regions in 2003/2004. Interviews were
      conducted and blood samples for routine purposes were collected and tested for
      anti-HIV IgG antibody anonymously, using Bionor HIV-1 & 2 assay. RESULTS: Among
      enrollees, 94% (1296/1377) participated fully. The overall prevalence of HIV was
      2.0% (95%CI: 1.34-2.97). The highest HIV prevalence was among women aged between
      15-19 years in both rural and remote rural populations. The odds of HIV infection
      was 4.3 (95%CI: 1.42-12.77) times among women reporting more than one lifetime
      sexual partners compared with those with one partner. HIV infection was
      associated with history of genital sores or foul smelling discharge, OR 6.8
      (95%CI: 2.78-16.66) and age at first pregnancy (2.5 times higher likelihood of
      infection if before the age of 18 years versus at a later age). CONCLUSION:
      Including rural remote sites, as part of the national ANC routine surveillance,
      is crucial in order to discover imminent silent epidemics such as the one
      described in this paper. Scaling up HIV prevention efforts is mandatory to
      prevent the imminent escalation of the HIV epidemic highly associated with a
      history of sexually transmitted infections (STIs), multiple sexual partners and
      pregnancies at a younger age. Ignorance of relevant knowledge and low utilisation
      of condoms underscores the urgency for large-scale preventive efforts. Research
      to capture a wider representation of the risk factors in the general population
      should be a priority to enable further customised HIV prevention efforts.

PMID- 16643654
TI  - A coding polymorphism in matrix metalloproteinase 9 reduces risk of scarring
      sequelae of ocular Chlamydia trachomatis infection.
AB  - BACKGROUND: Trachoma, an infectious disease of the conjunctiva caused by
      Chlamydia trachomatis, is an important global cause of blindness. A dysregulated
      extracellular matrix (ECM) proteolysis during the processes of tissue repair
      following infection and inflammation are thought to play a key role in the
      development of fibrotic sequelae of infection, which ultimately leads to
      blindness. Expression and activity of matrix metalloproteinase 9 (MMP-9), a major
      effector of ECM turnover, is up-regulated in the inflamed conjunctiva of trachoma
      subjects. Genetic variation within the MMP9 gene affects in vitro MMP9 expression
      levels, enzymatic activity and susceptibility to various inflammatory and
      fibrotic conditions. METHODS: We genotyped 651 case-control pairs from trachoma
      endemic villages in The Gambia for coding single nucleotide polymorphisms (SNPs)
      in the MMP9 gene using the high-throughput Sequenom system. Single marker and
      haplotype conditional logistic regression (CLR) analysis for disease association
      was performed. RESULTS: The Q279R mutation located in exon 6 of MMP9 was found to
      be associated with lower risk for severe disease sequelae of ocular Chlamydia
      trachomatis infection. This mutation, which leads to a nonsynonymous amino-acid
      change within the active site of the enzyme may reduce MMP-9-induced degradation
      of the structural components of the ECM during inflammatory episodes in trachoma
      and its associated fibrosis. CONCLUSION: This work supports the hypothesis that
      MMP-9 has a role in the pathogenesis of blinding trachoma.

PMID- 16643655
TI  - The molecular portraits of breast tumors are conserved across microarray
      platforms.
AB  - BACKGROUND: Validation of a novel gene expression signature in independent data
      sets is a critical step in the development of a clinically useful test for cancer
      patient risk-stratification. However, validation is often unconvincing because
      the size of the test set is typically small. To overcome this problem we used
      publicly available breast cancer gene expression data sets and a novel approach
      to data fusion, in order to validate a new breast tumor intrinsic list. RESULTS:
      A 105-tumor training set containing 26 sample pairs was used to derive a new
      breast tumor intrinsic gene list. This intrinsic list contained 1300 genes and a
      proliferation signature that was not present in previous breast intrinsic gene
      sets. We tested this list as a survival predictor on a data set of 311 tumors
      compiled from three independent microarray studies that were fused into a single
      data set using Distance Weighted Discrimination. When the new intrinsic gene set
      was used to hierarchically cluster this combined test set, tumors were grouped
      into LumA, LumB, Basal-like, HER2+/ER-, and Normal Breast-like tumor subtypes
      that we demonstrated in previous datasets. These subtypes were associated with
      significant differences in Relapse-Free and Overall Survival. Multivariate Cox
      analysis of the combined test set showed that the intrinsic subtype
      classifications added significant prognostic information that was independent of
      standard clinical predictors. From the combined test set, we developed an
      objective and unchanging classifier based upon five intrinsic subtype mean
      expression profiles (i.e. centroids), which is designed for single sample
      predictions (SSP). The SSP approach was applied to two additional independent
      data sets and consistently predicted survival in both systemically treated and
      untreated patient groups. CONCLUSION: This study validates the "breast tumor
      intrinsic" subtype classification as an objective means of tumor classification
      that should be translated into a clinical assay for further retrospective and
      prospective validation. In addition, our method of combining existing data sets
      can be used to robustly validate the potential clinical value of any new gene
      expression profile.

PMID- 16643656
TI  - Primary mediastinal hemangiopericytoma.
AB  - BACKGROUND: Hemangiopericytoma is a rare mesenchymal neoplasm, accounting for
      about 1% of vascular tumors The tumor occurs most commonly in the skin,
      subcutaneous soft tissues, muscles of the extremities, retroperitoneum but rarely
      in the lung, trachea or mediastinum. CASE PRESENTATION: A rare case of primary
      mediastinal hemangiopericytoma is presented. A 72-year-old woman was treated by
      complete surgical resection of the tumor. Details of the clinical and
      radiographic feature are presented. The patient's postoperative course was
      uneventful with no evidence of recurrence 9 months after the operation.
      CONCLUSION: Hemangiopericytoma is an uncommon, potentially malignant tumor
      originating from pericytes in the small vessels and surgical radical excision is
      the treatment of choice, although the criteria for determining the area of
      resection have not been established. International literature has demonstrated
      that recurrent disease usually occurs within 2 years and therefore a long-term
      careful follow-up is required.

PMID- 16643657
TI  - A stable gene selection in microarray data analysis.
AB  - BACKGROUND: Microarray data analysis is notorious for involving a huge number of
      genes compared to a relatively small number of samples. Gene selection is to
      detect the most significantly differentially expressed genes under different
      conditions, and it has been a central research focus. In general, a better gene
      selection method can improve the performance of classification significantly. One
      of the difficulties in gene selection is that the numbers of samples under
      different conditions vary a lot. RESULTS: Two novel gene selection methods are
      proposed in this paper, which are not affected by the unbalanced sample class
      sizes and do not assume any explicit statistical model on the gene expression
      values. They were evaluated on eight publicly available microarray datasets,
      using leave-one-out cross-validation and 5-fold cross-validation. The performance
      is measured by the classification accuracies using the top ranked genes based on
      the training datasets. CONCLUSION: The experimental results showed that the
      proposed gene selection methods are efficient, effective, and robust in
      identifying differentially expressed genes. Adopting the existing SVM-based and
      KNN-based classifiers, the selected genes by our proposed methods in general give
      more accurate classification results, typically when the sample class sizes in
      the training dataset are unbalanced.

PMID- 16643658
TI  - Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian
      gene expression data.
AB  - BACKGROUND: A key step in the regulation of gene expression is the sequence
      specific binding of transcription factors (TFs) to their DNA recognition sites.
      However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been
      challenging, even when employing cross-species sequence conservation. We
      hypothesized that for human and mouse, many orthologous genes expressed in a
      similarly tissue-specific manner in both human and mouse gene expression data,
      are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs
      present within noncoding sequence conserved between these genomes. RESULTS: We
      performed automated motif searching and merging across four different motif
      finding algorithms, followed by filtering of the resulting motifs for those that
      contain blocks of information content. Applying this motif finding strategy to
      conserved noncoding regions surrounding co-expressed tissue-specific human genes
      allowed us to discover both previously known, and many novel candidate,
      regulatory DNA motifs in all 18 tissue-specific expression clusters that we
      examined. For previously known TFBS motifs, we observed that if a TF was
      expressed in the specified tissue of interest, then in most cases we identified a
      motif that matched its TRANSFAC motif; conversely, of all those discovered motifs
      that matched TRANSFAC motifs, most of the corresponding TF transcripts were
      expressed in the tissue(s) corresponding to the expression cluster for which the
      motif was found. CONCLUSION: Our results indicate that the integration of the
      results from multiple motif finding tools identifies and ranks highly more known
      and novel motifs than does the use of just one of these tools. In addition, we
      believe that our simultaneous enrichment strategies helped to identify likely
      human cis regulatory elements. A number of the discovered motifs may correspond
      to novel binding site motifs for as yet uncharacterized tissue-specific TFs. We
      expect this strategy to be useful for identifying motifs in other metazoan
      genomes.

PMID- 16643659
TI  - Modulation of integrin-linked kinase (ILK) expression in human oesophageal
      squamous cell carcinoma cell lines by the EGF and TGFbeta1 growth factors.
AB  - BACKGROUND: Integrin-linked kinase (ILK) is a ubiquitously expressed protein
      kinase that has emerged as one of the points of convergence between integrin- and
      growth factor-signalling pathways. RESULTS: In this study we identify the ILK
      isoform expressed in five human oesophageal squamous cell carcinoma cell lines of
      South African origin as ILK1, and demonstrate its cellular distribution. ILK
      expression, although similar in the majority of the cell lines, did show
      variation. Furthermore, the ILK expressed was shown to be catalytically
      functional. The effect of growth factors on ILK expression was examined. An
      increase in ILK expression, following EGF and TGFbeta1 exposure, was a trend
      across all the five oesophageal carcinoma cell lines tested. CONCLUSION: These
      results suggest that growth factor modulation of ILK expression relies on the
      internalisation/recycling of growth factor receptors and stimulation of the PI3K
      pathway, which may have implications with regards to cell adhesion and
      tumourigenesis.

PMID- 16643660
TI  - Health inequality in adolescence. Does stratification occur by familial social
      background, family affluence, or personal social position?
AB  - BACKGROUND: Two new sets of stratification indicators--family's material
      affluence and adolescent's personal social position- were compared with
      traditional indicators of familial social position based on parental occupation
      and education for their ability to detect health inequality among adolescents.
      METHODS: Survey data were collected in the Adolescent Health and Lifestyle Survey
      in 2003 from nationally representative samples of 12-, 14- and 16-year-old Finns
      (number of respondents 5394, response rate 71%). Indicators of the familial
      social position were father's socio-economic status, parents' education, parents'
      labour market position. Indicators of material affluence were number of cars,
      vacation travels, and computers in the family, own room and amount of weekly
      spending money. Adolescent's personal social position was measured as school
      performance. Measures of health were long-standing illness, overweight, use of
      mental health services, poor self-rated health and number of weekly health
      complaints. Ordinal logistic regression analysis was applied to study the
      associations between stratification indicators and health variables. RESULTS: All
      three groups of indicators of social stratification showed inequality in health,
      but the strongest associations were observed with the adolescent's personal
      social position. Health inequality was only partly identifiable by the
      traditional indicators of familial social position. The direction of the
      inequality was as expected when using the traditional indicators or personal
      social position: adolescents from higher social positions were healthier than
      those from lower positions. The indicators of family's material affluence showed
      mainly weak or no association with health and some of the indicators were
      inversely associated, although weakly. CONCLUSION: In addition to traditional
      indicators describing the socio-structural influences on the distribution of
      health among adolescents, indicators of family's material affluence should be
      further developed. Adolescents' personal social position should be included in
      the studies of health inequalities.

PMID- 16643661
TI  - Learners' decisions for attending Pediatric Grand Rounds: a qualitative and
      quantitative study.
AB  - BACKGROUND: Although grand rounds plays a major educational role at academic
      medical centers, there has been little investigation into the factors influencing
      the learners' decision to attend. Greater awareness of attendees' expectations
      may allow grand rounds planners to better accommodate the learners' perspective,
      potentially making continuing education activities more attractive and inviting.
      METHODS: We used both qualitative (part A) and quantitative (part B) techniques
      to investigate the motivators and barriers to grand rounds attendance. Part A
      investigated contextual factors influencing attendance as expressed through
      attendee interviews. Transcripts of the interviews were analyzed using grounded
      theory techniques. We created a concept map linking key factors and their
      relationships. In part B we quantified the motivators and barriers identified
      during the initial interviews through a survey of the grand rounds audience.
      RESULTS: Sixteen persons voluntarily took part in the qualitative study (part A)
      by participating in one of seven group interview sessions. Of the 14 themes that
      emerged from these sessions, the most frequent factors motivating attendance
      involved competent practice and the need to know. All sessions discussed
      intellectual stimulation, social interaction, time constraints and convenience,
      licensure, content and format, and absence of cost for attending sessions. The 59
      respondents to the survey (part B) identified clinically-useful topics (85%),
      continuing education credit (46%), cutting-edge research (27%), networking (22%),
      and refreshments (8%) as motivators and non-relevant topics (44%) and too busy to
      attend (56%) as barriers. CONCLUSION: Greater understanding of the consumers'
      perspective can allow planners to tailor the style, content, and logistics to
      make grand rounds more attractive and inviting.

PMID- 16643662
TI  - Time to positivity in blood cultures of adults with Streptococcus pneumoniae
      bacteremia.
AB  - BACKGROUND: previous studies have established that bacterial blood concentration
      is related with clinical outcome. Time to positivity of blood cultures (TTP) has
      relationship with bacterial blood concentration and could be related with
      prognosis. As there is scarce information about the usefulness of TTP, we study
      the relationship of TTP with clinical parameters in patients with Streptococcus
      pneumoniae bacteremia. METHODS: TTP of all cases of Streptococcus pneumoniae
      bacteremia, detected between January 1995 and December 2004 using the BacT/Alert
      automated blood culture system in a teaching community hospital was analyzed.
      When multiple cultures were positive only the shortest TTP was selected for the
      analysis. RESULTS: in the study period 105 patients with Streptococcus pneumoniae
      bacteremia were detected. Median TTP was 14.1 hours (range 1.2 h to 127 h).
      Immunosuppressed patients (n = 5), patients with confusion (n = 19), severe
      sepsis or shock at the time of blood culture extraction (n = 12), those with a
      diagnosis of meningitis (n = 7) and those admitted to the ICU (n = 14) had lower
      TTP. Patients with TTP in the first quartile were more frequently hospitalized,
      admitted to the ICU, had meningitis, a non-pneumonic origin of the bacteremia,
      and a higher number of positive blood cultures than patients with TTP in the
      fourth quartile. None of the patients with TTP in the 90th decile had any of
      these factors associated with shorter TTP, and eight out of ten patients with TTP
      in the 10th decile had at least one of these factors. The number of positive
      blood cultures had an inverse correlation with TTP, suggesting a relationship of
      TTP with bacterial blood concentration. CONCLUSION: Our data support the
      relationship of TTP with several clinical parameters in patients with
      Streptococcus pneumoniae bacteremia, and its potential usefulness as a surrogate
      marker of outcome.

PMID- 16643663
TI  - Self-reported safety belt use among emergency department patients in Boston,
      Massachusetts.
AB  - BACKGROUND: Safety belt use is 80% nationally, yet only 63% in Massachusetts.
      Safety belt use among potentially at-risk groups in Boston is unknown. We sought
      to assess the prevalence and correlates of belt non-use among emergency
      department (ED) patients in Boston. METHODS: A cross-sectional survey with
      systematic sampling was conducted on non-urgent ED patients age > or = 18. A
      closed-ended survey was administered by interview. Safety belt use was defined
      via two methods: a single-item and a multiple-item measure of safety belt use.
      Each was scored using a 5-point frequency scale. Responses were used to
      categorize safety belt use as 'always' or less than 'always'. Outcome for
      multivariate logistic regression analysis was safety belt use less than 'always'.
      RESULTS: Of 478 patients approached, 381 (80%) participated. Participants were
      48% female, 48% African-American, 40% White, median age 39. Among participants,
      250 (66%) had been in a car crash; 234 (61%) had a valid driver's license, and 42
      (11%) had been ticketed for belt non-use. Using two different survey measures, a
      single-item and a multiple-item measure, safety belt use 'always' was 51% and 36%
      respectively. According to separate regression models, factors associated with
      belt non-use included male gender, alcohol consumption >5 drinks in one episode,
      riding with others that drink and drive, ever receiving a citation for belt non
      use, believing that safety belt use is 'uncomfortable', and that 'I just forget',
      while 'It's my usual habit' was protective. CONCLUSION: ED patients at an urban
      hospital in Boston have considerably lower self-reported safety belt use than
      state or national estimates. An ED-based intervention to increase safety belt use
      among this hard-to-reach population warrants consideration.

PMID- 16643664
TI  - Primary histologic diagnosis using automated whole slide imaging: a validation
      study.
AB  - BACKGROUND: Only prototypes 5 years ago, high-speed, automated whole slide
      imaging (WSI) systems (also called digital slide systems, virtual microscopes or
      wide field imagers) are becoming increasingly capable and robust. Modern devices
      can capture a slide in 5 minutes at spatial sampling periods of less than 0.5
      micron/pixel. The capacity to rapidly digitize large numbers of slides should
      eventually have a profound, positive impact on pathology. It is important,
      however, that pathologists validate these systems during development, not only to
      identify their limitations but to guide their evolution. METHODS: Three
      pathologists fully signed out 25 cases representing 31 parts. The laboratory
      information system was used to simulate real-world sign-out conditions including
      entering a full diagnostic field and comment (when appropriate) and ordering
      special stains and recuts. For each case, discrepancies between diagnoses were
      documented by committee and a "consensus" report was formed and then compared
      with the microscope-based, sign-out report from the clinical archive. RESULTS: In
      17 of 25 cases there were no discrepancies between the individual study
      pathologist reports. In 8 of the remaining cases, there were 12 discrepancies,
      including 3 in which image quality could be at least partially implicated. When
      the WSI consensus diagnoses were compared with the original sign-out diagnoses,
      no significant discrepancies were found. Full text of the pathologist reports,
      the WSI consensus diagnoses, and the original sign-out diagnoses are available as
      an attachment to this publication. CONCLUSION: The results indicated that the
      image information contained in current whole slide images is sufficient for
      pathologists to make reliable diagnostic decisions and compose complex diagnostic
      reports. This is a very positive result; however, this does not mean that WSI is
      as good as a microscope. Virtually every slide had focal areas in which image
      quality (focus and dynamic range) was less than perfect. In some cases, there was
      evidence of over-compression and regions made "soft" by less than perfect focus.
      We expect systems will continue to get better, image quality and speed will
      continue to improve, but that further validation studies will be needed to guide
      development of this promising technology.

PMID- 16643665
TI  - Parameter estimation for stiff equations of biosystems using radial basis
      function networks.
AB  - BACKGROUND: The modeling of dynamic systems requires estimating kinetic
      parameters from experimentally measured time-courses. Conventional global
      optimization methods used for parameter estimation, e.g. genetic algorithms (GA),
      consume enormous computational time because they require iterative numerical
      integrations for differential equations. When the target model is stiff, the
      computational time for reaching a solution increases further. RESULTS: In an
      attempt to solve this problem, we explored a learning technique that uses radial
      basis function networks (RBFN) to achieve a parameter estimation for biochemical
      models. RBFN reduce the number of numerical integrations by replacing derivatives
      with slopes derived from the distribution of searching points. To introduce a
      slight search bias, we implemented additional data selection using a GA that
      searches data-sparse areas at low computational cost. In addition, we adopted
      logarithmic transformation that smoothes the fitness surface to obtain a solution
      simply. We conducted numerical experiments to validate our methods and compared
      the results with those obtained by GA. We found that the calculation time
      decreased by more than 50% and the convergence rate increased from 60% to 90%.
      CONCLUSION: In this work, our RBFN technique was effective for parameter
      optimization of stiff biochemical models.

PMID- 16643666
TI  - Differences in MAP kinase phosphorylation in response to mechanical strain in
      asthmatic fibroblasts.
AB  - BACKGROUND: Mechanical strain alters protein expression. It results in
      phosphorylation of MAP kinases and up-regulation of extracellular matrix
      proteins. We investigated whether phosphorylation of MAP kinase family members
      was increased in response to mechanical strain in fibroblasts from asthmatic
      patients (AF) and normal controls (NF), and whether phosphorylation of these
      signaling molecules would be different in the two cell populations. METHODS:
      Fibroblasts were obtained from mild, atopic asthmatics and non-atopic volunteers
      using endobronchial biopsy. Cells were grown on flexible, collagen I-coated
      membranes, and subjected to mechanical strain (Flexercell). MAP kinase
      phosphorylation was measured at baseline, and during one hour of strain. We also
      examined the effect of strain on proteoglycan production. RESULTS: At baseline,
      there was increased phosphorylation of ERK1/2 and p38, and decreased
      phosphorylation of JNK in AF vs NF. During strain in NF, p38 phosphorylation was
      increased. Conversely in AF, strain resulted in an increase in JNK
      phosphorylation, had no effect on phosphorylation of p38, and resulted in a
      decrease in ERK1/2 phosphorylation. There was a significant increase in versican
      protein production after 24 h strain in both AF and NF. JNK inhibition reversed
      the strain-induced increase in versican in NF, but had no effect in AF.
      CONCLUSION: These results show that there are phenotypic differences in MAP
      kinase phosphorylation in AF vs NF, and that different signaling pathways are
      involved in transducing mechanical stimuli in these two populations of cells.

PMID- 16643667
TI  - Histological staining methods preparatory to laser capture microdissection
      significantly affect the integrity of the cellular RNA.
AB  - BACKGROUND: Gene expression profiling by microarray analysis of cells enriched by
      laser capture microdissection (LCM) faces several technical challenges. Frozen
      sections yield higher quality RNA than paraffin-imbedded sections, but even with
      frozen sections, the staining methods used for histological identification of
      cells of interest could still damage the mRNA in the cells. To study the
      contribution of staining methods to degradation of results from gene expression
      profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor
      cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning
      for LCM and subsequent RNA extraction. We used microarray hybridization analysis
      to compare gene expression profiles of RNA from cell pellets with gene expression
      profiles of RNA from frozen sections that had been stained with hematoxylin and
      eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with
      the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were
      amplified with two rounds of T7-based in vitro transcription and analyzed by two
      color expression analysis on 10-K cDNA microarrays. RESULTS: The MGP-stained
      samples showed the least introduction of mRNA loss, followed by H&E and
      immunofluorescence. Nissl staining was significantly more detrimental to gene
      expression profiles, presumably owing to an aqueous step in which RNA may have
      been damaged by endogenous or exogenous RNAases. CONCLUSION: RNA damage can occur
      during the staining steps preparatory to laser capture microdissection, with the
      consequence of loss of representation of certain genes in microarray
      hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining
      solutions appears to be important in protecting RNA from loss of gene
      transcripts.

PMID- 16643668
TI  - The prevention of anaphylactoid reactions to iodinated radiological contrast
      media: a systematic review.
AB  - BACKGROUND: Anaphylactoid reactions to iodinated contrast media are relatively
      common and potentially life threatening. Opinion is divided as to the utility of
      medications for preventing these reactions. We performed a systematic review to
      assess regimes for the prevention of anaphylactoid reactions to iodinated
      contrast media. METHODS: Searches for studies were conducted in the Medline,
      EMBASE, CINAHL and CENTRAL databases. Bibliographies of included studies and
      review articles were examined and experts were contacted. Randomised clinical
      trials that examined agents given prior to iodinated contrast material for the
      prevention of anaphylactoid reactions were included in the review. The validity
      of the included studies was examined using a component approach. RESULTS: Six
      studies met the inclusion criteria, but only one of these fulfilled all of the
      validity criteria. There were four studies that examined the use of H1
      antihistamines, each was used to prevent anaphylactoid reactions to ionic
      contrast. The random effects pooled relative risk demonstrated a significant
      reduction in the overall rate of anaphylactoid reactions (RR = 0.4, 95% CI 0.18
      0.9, p = 0.027). There were insufficient studies to produce a pooled statistic
      for the use of corticosteroids, however regimes of steroids (methylprednisolone
      32 mg) given at least six hours and again two hours prior to the administration
      of contrast suggested a reduction in the incidence of anaphylactoid reactions.
      CONCLUSION: In conclusion, there are few high quality randomised clinical trials
      that have addressed the question of the optimal methods to prevent allergic type
      reactions to iodinated radiological contrast media. Allowing for these
      limitations, the results suggest that H1 antihistamines given immediately prior
      to the administration of ionic contrast may be useful in preventing reactions to
      ionic contrast and are suggestive of a protective effect of corticosteroids when
      given in two doses at least six hours prior and again two hours prior to the
      administration of contrast, both ionic and non-ionic. These agents should be
      considered for use in patients who are at high risk of an anaphylactoid reaction
      to contrast media and for who prophylactic therapy is considered necessary.
      Further research is needed before definitive recommendations can be made.

PMID- 16643669
TI  - Simplifying gene trees for easier comprehension.
AB  - BACKGROUND: In the genomic age, gene trees may contain large amounts of data
      making them hard to read and understand. Therefore, an automated simplification
      is important. RESULTS: We present a simplification tool for gene trees called
      TreeSimplifier. Based on species tree information and HUGO gene names, it
      summarizes "monophyla". These monophyla correspond to subtrees of the gene tree
      where the evolution of a gene follows species phylogeny, and they are simplified
      to single leaves in the gene tree. Such a simplification may fail, for example,
      due to genes in the gene tree that are misplaced. In this way, misplaced genes
      can be identified. Optionally, our tool glosses over a limited degree of
      "paraphyly" in a further simplification step. In both simplification steps,
      species can be summarized into groups and treated as equivalent. In the present
      study we used our tool to derive a simplified tree of 397 leaves from a tree of
      1138 leaves. Comparing the simplified tree to a "cartoon tree" created manually,
      we note that both agree to a high degree. CONCLUSION: Our automatic
      simplification tool for gene trees is fast, accurate, and effective. It yields
      results of similar quality as manual simplification. It should be valuable in
      phylogenetic studies of large protein families. The software is available at
      http://www.uni-muenster.de/Bioinformatics/services/treesim/.

PMID- 16643670
TI  - Publishing proteomic data.
AB  - Scientific publications should provide sufficient detail in terms of methodology
      and presented data to enable the community to reproduce the methodology to
      generate similar data and arrive at the same conclusion, if an identical sample
      is provided for analysis. The advent of high-throughput methods in biological
      experimentation impose some unique challenges both in data presentation in
      classical print format, as well as in describing methodology and data analysis in
      sufficient detail to conform to good publication practice. To facilitate this
      process, Proteome Science is adopting a set of methodology and data presentation
      guidelines to enable both peer reviewers, as well as the scientific community, to
      better evaluate high-throughput proteomic studies.

PMID- 16643671
TI  - Identification, cloning and functional characterization of novel sperm associated
      antigen 11 (SPAG11) isoforms in the rat.
AB  - BACKGROUND: Sperm binding proteins and their C-terminal peptides of the Sperm
      Associated Antigen 11 (SPAG11) family were found to play an important role in
      epididymal innate immunity in addition to their role in sperm maturation.
      However, the expression of Spag11 transcripts in rodents is not well documented.
      METHODS: Computational analysis was employed to identify novel Spag11 isoforms in
      the rat. RT-PCR analyses were carried out on RNAs isolated from the male
      reproductive tract tissues of rat using gene specific primers for Spag11c and
      Spag11t. The identities of PCR products were confirmed by sequencing. Tissue
      distribution, developmental expression and androgen regulation of Spag11t and
      Spag11c were studied using RT-PCR. The antimicrobial activities of recombinant
      Spag11t and Spag11c were tested against E coli in a colony forming unit assay.
      RESULTS: In this study, we identified two novel Spag11 transcripts, namely,
      Spag11t and Spag11c derived from the long arm of chromosome 16 in the rat (Rattus
      norvegicus), using both in silico and molecular biology approaches. Spag11c is
      expressed in all three regions of the epididymis, in testis and in ovary but is
      absent from the seminal vesicle. Spag11t expression is confined to the caput and
      it is not expressed in the testis, seminal vesicle or ovary. Age dependent
      expression of Spag11t and Spag11c was observed in the epididymides of rats (10-60
      day old). Their expression was found to be most abundant in the adult rat (60
      day) suggesting roles in mature reproductive function. Further, both Spag11t and
      Spag11c expression was down regulated in castrated rat epididymides and the
      expression was maintained in the testosterone replaced castrated rats. SPAG11C is
      a potent antibacterial agent. SPAG11T also displayed bactericidal capacity
      although weaker than SPAG11C and SPAG11E. CONCLUSION: The abundant expression of
      Spag11t and Spag11c in the male reproductive tract suggests an important role in
      male reproductive tract immunity. Their expression is developmentally regulated
      and androgen dependent. Characterization of novel SPAG11 isoforms will contribute
      to our understanding of the role of epididymal proteins in sperm maturation and
      innate immunity.

PMID- 16643672
TI  - Design of microarray probes for virus identification and detection of emerging
      viruses at the genus level.
AB  - BACKGROUND: Most virus detection methods are geared towards the detection of
      specific single viruses or just a few known targets, and lack the capability to
      uncover the novel viruses that cause emerging viral infections. To address this
      issue, we developed a computational method that identifies the conserved viral
      sequences at the genus level for all viral genomes available in GenBank, and
      established a virus probe library. The virus probes are used not only to identify
      known viruses but also for discerning the genera of emerging or uncharacterized
      ones. RESULTS: Using the microarray approach, the identity of the virus in a test
      sample is determined by the signals of both genus and species-specific probes.
      The genera of emerging and uncharacterized viruses are determined based on
      hybridization of the viral sequences to the conserved probes for the existing
      viral genera. A detection and classification procedure to determine the identity
      of a virus directly from detection signals results in the rapid identification of
      the virus. CONCLUSION: We have demonstrated the validity and feasibility of the
      above strategy with a small number of viral samples. The probe design algorithm
      can be applied to any publicly available viral sequence database. The strategy of
      using separate genus and species probe sets enables the use of a straightforward
      virus identity calculation directly based on the hybridization signals. Our virus
      identification strategy has great potential in the diagnosis of viral infections.
      The virus genus and specific probe database and the associated summary tables are
      available at http://genestamp.sinica.edu.tw/virus/index.htm.

PMID- 16643673
TI  - PDA: Pooled DNA analyzer.
AB  - BACKGROUND: Association mapping using abundant single nucleotide polymorphisms is
      a powerful tool for identifying disease susceptibility genes for complex traits
      and exploring possible genetic diversity. Genotyping large numbers of SNPs
      individually is performed routinely but is cost prohibitive for large-scale
      genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping
      method. However, no software has been developed for complete pooled-DNA analyses,
      including data standardization, allele frequency estimation, and
      single/multipoint DNA pooling association tests. This motivated the development
      of the software, 'PDA' (Pooled DNA Analyzer), to analyze pooled DNA data.
      RESULTS: We develop the software, PDA, for the analysis of pooled-DNA data. PDA
      is originally implemented with the MATLAB language, but it can also be executed
      on a Windows system without installing the MATLAB. PDA provides estimates of the
      coefficient of preferential amplification and allele frequency. PDA considers an
      extended single-point association test, which can compare allele frequencies
      between two DNA pools constructed under different experimental conditions.
      Moreover, PDA also provides novel chromosome-wide multipoint association tests
      based on p-value combinations and a sliding-window concept. This new multipoint
      testing procedure overcomes a computational bottleneck of conventional haplotype
      oriented multipoint methods in DNA pooling analyses and can handle data sets
      having a large pool size and/or large numbers of polymorphic markers. All of the
      PDA functions are illustrated in the four bona fide examples. CONCLUSION: PDA is
      simple to operate and does not require that users have a strong statistical
      background. The software is available at
      http://www.ibms.sinica.edu.tw/%7Ecsjfann/first%20flow/pda.htm.

PMID- 16643674
TI  - Astrocytes derived from glial-restricted precursors promote spinal cord repair.
AB  - BACKGROUND: Transplantation of embryonic stem or neural progenitor cells is an
      attractive strategy for repair of the injured central nervous system.
      Transplantation of these cells alone to acute spinal cord injuries has not,
      however, resulted in robust axon regeneration beyond the sites of injury. This
      may be due to progenitors differentiating to cell types that support axon growth
      poorly and/or their inability to modify the inhibitory environment of adult
      central nervous system (CNS) injuries. We reasoned therefore that pre
      differentiation of embryonic neural precursors to astrocytes, which are thought
      to support axon growth in the injured immature CNS, would be more beneficial for
      CNS repair. RESULTS: Transplantation of astrocytes derived from embryonic glial
      restricted precursors (GRPs) promoted robust axon growth and restoration of
      locomotor function after acute transection injuries of the adult rat spinal cord.
      Transplantation of GRP-derived astrocytes (GDAs) into dorsal column injuries
      promoted growth of over 60% of ascending dorsal column axons into the centers of
      the lesions, with 66% of these axons extending beyond the injury sites. Grid-walk
      analysis of GDA-transplanted rats with rubrospinal tract injuries revealed
      significant improvements in locomotor function. GDA transplantation also induced
      a striking realignment of injured tissue, suppressed initial scarring and rescued
      axotomized CNS neurons with cut axons from atrophy. In sharp contrast,
      undifferentiated GRPs failed to suppress scar formation or support axon growth
      and locomotor recovery. CONCLUSION: Pre-differentiation of glial precursors into
      GDAs before transplantation into spinal cord injuries leads to significantly
      improved outcomes over precursor cell transplantation, providing both a novel
      strategy and a highly effective new cell type for repairing CNS injuries.

PMID- 16643675
TI  - Mycoplasma genitalium is associated with symptomatic urethritis.
AB  - In order to further investigate the epidemiology of Mycoplasma genitalium, 680
      men attending departments of genitourinary medicine in Bristol, Bath and Truro
      were studied. M. genitalium was detected in 36 men (5.3%) and was present at all
      three clinics. Clinically, both urethritis and the presence of a urethral
      discharge and/or dysuria, but not penile irritation were independently associated
      with the detection of M. genitalium, the former being with the strongest
      association (odds ratio [OR] 10.76, 95% confidence interval [CI] [3.10-37.29], P
      < 0.0001; OR 3.01, 95% CI [1.28-7.05], P = 0.011 and OR 1.28, 95% CI [0.61-2.69],
      P = 0.51, respectively). In men with urethritis, those with a discharge and/or
      dysuria were more likely to have M. genitalium detected (OR 2.61, 95% CI [1.09
      6.25], P = 0.032). We found no association with younger age or a recent change of
      sexual partner. In conclusion, M. genitalium is associated with symptomatic
      urethritis.

PMID- 16643676
TI  - Quantifying leukocytes in first catch urine provides new insights into our
      understanding of symptomatic and asymptomatic urethritis.
AB  - We quantitatively investigated inflammatory cells in the male urethra. Leukocytes
      in the first catch urine (FCU) from 87 men with and without urethritis were
      quantitated using haemocytometer counts and stained with an anti-CD45 pan
      leukocyte antibody. An increased number of leukocytes in FCU specimens was
      associated with urethritis (P > 0.002), the presence of discharge and/or dysuria
      (P < 0.001), and detection of Chlamydia trachomatis (P < 0.001) and Neisseria
      gonorrhoeae (P < 0.001). In men with urethritis, higher leukocyte counts were
      also observed in the above groups (P = 0.07, 0.03 and P < 0.0001, respectively).
      As leukocyte number increased, the likelihood of detecting either pathogen
      increased. This study suggests that symptoms and signs are a surrogate marker for
      the degree of inflammation present, and that as urethral inflammation increases,
      the likelihood of detecting a sexually transmitted pathogen also increases. This
      would explain why men with asymptomatic urethritis are less likely to have a
      sexually transmitted infection detected than those with discharge and/or dysuria.

PMID- 16643677
TI  - Non-chlamydial non-gonococcal urethritis or undiagnosed chlamydial urethritis?
AB  - The aim of this study is to investigate the prevalence of sexually transmitted
      infections (STI) in the partners of men with non-chlamydial, non-gonococcal
      urethritis (NCNGU). Observational study of the sexual partners of men with NCNGU
      diagnosed in the Department of Genitourinary Medicine, Edinburgh between 1 June
      2002 and 31 December 2003. The diagnosis of chlamydial infection was based on
      ligase chain reaction (LCx) between June 2002 and March 2003, and on polymerase
      chain reaction (PCR) thereafter. Gonococcal infection was diagnosed with culture
      method.Sexual partners of 99 (25%) of the 403 heterosexual men diagnosed with
      NCNGU were screened. Chlamydial infection was detected in 19 (19%) of the female
      sexual partners. Higher proportion of female partners of symptomatic men (15/51)
      had chlamydial infection compared with that of partners of asymptomatic men
      (4/48) (P < 0.005).NCNGU may be related to false-negative results of chlamydial
      diagnostic tests. Screening and treatment of sexual partners of men with NCNGU is
      therefore necessary.

PMID- 16643678
TI  - Factors associated with anxiety in patients attending a sexually transmitted
      infection clinic: qualitative survey.
AB  - We used qualitative methods to explore factors, which might explain increased
      anxiety in patients attending a sexually transmitted infection (STI) clinic.
      Twenty patients, who scored significantly for anxiety on the Hospital Anxiety and
      Depression Scale (HADS) attended a 20-minute interview. This explored factors
      contributing to their current psychological symptoms. Transcripts revealed three
      main themes. First were factors related to possible STIs and the clinic visit.
      These included health anxieties about HIV or fertility and clinic factors,
      including staff attitudes and clinic location. Second were factors unrelated to
      the clinic, including previous emotional difficulties or substance misuse. Third
      were issues concerning stigma, embarrassment and shame. The origins of anxiety in
      STI patients are multifactorial and difficult to identify during brief
      appointments. Despite modern clinics and attitudes, stigma and embarrassment
      remain prominent. Interventions to address these factors could improve
      psychological health in this patient group.

PMID- 16643679
TI  - Prevalence of sexually transmitted infections among long-distance truck drivers
      in Tongling, China.
AB  - Little is known about sexually transmitted infections (STIs), including HIV,
      among truck drivers in China. A cross-sectional study was conducted among truck
      drivers in Tongling of Anhui Province. A total of 550 truck drivers were
      interviewed with a structured questionnaire, and blood samples were collected and
      tested for HIV, syphilis, and herpes simplex virus 2 (HSV-2), and urine specimens
      for Neisseria gonorrhoeae and Chlamydia trachomatis. Prevalence was 10.6% for C.
      trachomatis and 8.1% for N. gonorrhoeae. Antibodies for syphilis were found in
      0.7% and for HSV-2 in 4.4%, and none was positive for HIV. About 92 (17.4%) truck
      drivers had at least one STI. There was no statistically significant association
      between sociodemographic, occupation or behavioural variables and the presence of
      a positive test for any STI. Our study suggests a high prevalence of STIs,
      particularly bacterial infections, among the truck drivers, indicating the need
      for health education, behavioural change interventions and STI care services in
      this population.

PMID- 16643680
TI  - An investigation of concurrent sex partnering in two samples of drug users having
      large numbers of sex partners.
AB  - The objective of this study was to quantitatively measure the nature of
      concurrent sex partnering in two samples of drug users having large numbers of
      sex partners. The purpose of this study was to measure concurrent sex partnering
      and overlap in concurrent sex partners in two samples of drug users in which some
      or all participants were trading sex-for-money. Two samples having large numbers
      of sex partners were used to conduct the analyses: drug-using male sex workers
      (MSW) and male and female crack cocaine smokers (CS) having vaginal sex. To
      reflect the quality of concurrent partnering, three measures were used: the
      proportion of the samples having concurrent partners; the proportions of the
      samples having intimate, casual, and sex-for-money of partners; and overlap in
      concurrent partners. Proportions of each sample having concurrent partners were
      essentially the same. However, the kinds of concurrent partners and overlap in
      concurrent partners were significantly different. Concurrent partners in the MSW
      sample were mostly sex-for-money or sex-for-drugs partners. Most concurrent
      partners in the CS sample were initimate or casual sex partners. Overlap in
      concurrent partners was also significantly different. The measure of overlap for
      the CS sample was three times higher than that of the MSW sample. These data
      suggest that concurrent sex partnering in the two samples, beyond the proportion
      having concurrent partners, was different. The patterns of concurrent sex
      partners in each sample may reflect different reasons for engaging in concurrent
      partnering. Different reasons for engaging in concurrent partnering may also be
      reflected in different overlap scores between the two samples. Efforts should be
      made in future studies to better capture the complexities of concurrent
      partnering and to examine the implications of these for disease spread and
      control.

PMID- 16643681
TI  - Criminal prosecutions for HIV transmission: people living with HIV respond.
AB  - This paper presents an analysis of responses to the first criminal convictions
      for HIV transmission in England and Wales within a sample of people living with
      HIV. These findings represent an important contribution to the development of
      well-informed prosecution policy. The responses were collected during 20 focused
      group discussions with a community and web-recruited sample of heterosexual
      African men and women, and gay and bisexual men (n = 125) living with diagnosed
      HIV in London, Manchester and Brighton. The vast majority (90%) of comments made
      were critical of the implementation and impact of criminalization. In particular,
      respondents expressed concern about the way in which criminal convictions
      conflict with messages about shared responsibility for 'safer sex', and the
      extent to which such cases will exacerbate existing stigma and discrimination
      related to HIV. Most felt that the successes achieved by human rights approaches
      to HIV prevention, treatment, and care were placed under threat by the growing
      culture of blame encouraged by criminal prosecutions.

PMID- 16643682
TI  - Sex work practices and condom use in female sex workers in Sydney.
AB  - The aim of this study was to determine sex work practices and predictors of
      condom use among female sex workers (SWs) in Sydney. SWs from two centres
      completed a self-administered questionnaire covering demographic and sexual
      characteristics and sex work practices. One hundred and forty-eight international
      (born in Asia) and 141 local SWs (born in Australia, New Zealand or the UK) were
      recruited. Local SWs saw more clients per shift than international SWs (P =
      0.002), but international SWs worked more shifts per week than local SWs (P =
      0.001). International SWs used condoms less consistently at work than local SWs
      (P = 0.001). About 37% of international SWs never used condoms with non-paying
      partners, compared with 14% of local SWs (P = 0.01). Speaking Thai (odds ratio
      [OR] 8.9, 95% confidence interval [CI]; 3.19-24.87) or Chinese (OR 17.4; 95% CI
      4.98-60.89) (both P < 0.001) and previous sex work in Thailand (OR 10.0 95% CI
      2.31-43.52; P = 0.02) were associated with inconsistent condom use. Strategies to
      improve condom use need to be evaluated.

PMID- 16643683
TI  - Epidemiological characteristics of HIV/AIDS in west China.
AB  - China is facing a major crisis because of the increasing epidemic of HIV/AIDS,
      especially in the western areas. The purpose of this paper is to enhance
      understanding of the crisis by analysing the published literature on the
      epidemiology, demographic features, routes of infection, and risk factors of
      HIV/AIDS infection in the 12 provinces in the west of China. HIV/AIDS has
      increased rapidly in recent years. The situation is urgent and requires
      comprehensive action. China's health care system is decentralized and under
      funded, and access to treatment by the poor is seriously limited. There is a lack
      of knowledge about HIV/AIDS in the general public and health care workers. The
      HIV/AIDS epidemic emerged initially in western areas of the country by means of
      intravenous drug use, but sexual risk behaviour and mother-to-child transmissions
      in the west of China are becoming important for HIV transmission.

PMID- 16643684
TI  - Co-infection with genital gonorrhoea and genital chlamydia in female sex workers
      in Yunnan, China.
AB  - An observational study on prevalence of co-infection with gonorrhoea and
      chlamydia was conducted among female sex workers (FSWs) in Kunming, China.A total
      of 505 FSWs participated in the study. All eligible participants gave informed
      consent. Demographic, behavioural and clinical information of the participants
      was gathered by direct structured interviews. Tampon swabs were collected to test
      for Chlamydia trachomatis and Nesseria gonorrhoeae. One-hundred and twenty-four
      (24.6%) FSWs were co-infected with these two pathogens. Of the 191 FSWs with
      gonorrhea, 124 (64.9%, 95% confidence interval [CI] = 57.9-71.3%) were co
      infected with chlamydia which was significantly higher than the proportion
      (41.9%, 95% CI = 36.4-47.6%) co-infected with gonorrhoea among 296 FSWs with
      chlamydia (P < 0.001). Only 47 of 191 (24.6%) FSWs with gonococcal infection and
      28 of 124 (22.6%) with co-infection with gonorrhoea and chlamydia reported
      vaginal discharge. The results of the study justify the recommendation in the
      national sexually transmitted disease (STD) guidelines that patients infected
      with gonorrhoea also be treated routinely with an anti-chlamydial regimen.
      However, a periodic mass treatment may be considered in some circumstances in STD
      control programmes to rapidly reduce the infections in this population.

PMID- 16643686
TI  - UK National Audit of Early Syphilis Management. Clinics audit: screening for and
      management of early syphilis.
AB  - Data were provided by 131 clinics, and 56% of cases were managed in clinics in
      the London regions in 2003. Three clinics (2%) do not routinely screen new
      patients for syphilis, and 28 clinics (21%) do not routinely screen 'rebook'
      patients who have had a new partner. More than 80% of clinics routinely conduct
      cardiovascular and neurological examinations, although chest radiography is only
      performed by 50% of clinics and lumbar puncture by 13%. Only 19 (14%) clinics
      indicated not routinely using the recommended procaine penicillin G (PPG) regimen
      or one- or two-dose benzathine penicillin G (BPG) regimens for early syphilis,
      with 57% providing two doses of BPG 2.4 g, 40% providing PPG 750 mg for 10 days,
      and 15% providing one dose of BPG 2.4 g. Only seven clinics (5%) indicated that
      they provided treatment for early syphilis with PPG that is inferior to that
      recommended in the national guidelines. Only 18 clinics specified using the
      recommended dose and duration (or in excess of this) of PPG for neurosyphilis for
      cases with HIV infection. Provision for management of severe penicillin reaction
      is good, although few patients are desensitized. All clinics report that contact
      tracing for early syphilis is provided, and is mainly the responsibility of
      health advisers. Compared with auditing outcomes, audit of management policies
      overestimated performance in contact tracing and provision of dark ground
      microscopy.

PMID- 16643687
TI  - Hypercalcaemia complicating immune reconstitution in an HIV-infected patient with
      disseminated tuberculosis.
AB  - An HIV positive man being treated for disseminated tuberculosis developed
      hypercalcaemia 17 days after starting highly active antiretroviral therapy
      (HAART). Hypercalcaemia resolved with stopping HAART and was thought to be due to
      immune reconstitution inflammatory syndrome.

PMID- 16643688
TI  - Atypical disseminated leishmaniasis resembling post-kala-azar dermal
      leishmaniasis in an HIV-infected patient.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is very uncommon among HIV-positive
      patients, and very few cases have so far been documented. A case of atypical
      disseminated leishmaniasis resembling PKDL in an HIV-positive patient
      successfully treated with N-methylglucamine antimoniate is reported. The
      polymerase chain reaction performed on the skin lesions was positive for
      Leishmania infantum.

PMID- 16643689
TI  - Is voluntary counselling and testing of drug users in China feasible?

PMID- 16643690
TI  - Diagnosis of herpetic cervicitis and concurrent sexually transmitted infections
      in primary genital herpes.

PMID- 16643691
TI  - Nurse-led asymptomatic screening clinics.

PMID- 16643692
TI  - Hopelessness at the end of life: the utility of the hopelessness scale with
      terminally ill cancer patients.
AB  - OBJECTIVES: We sought to investigate the utility of the Beck Hopelessness Scale
      (HS) in a sample of terminally ill cancer patients by examining the scale
      properties. Moreover, we sought to identify and remove potentially problematic
      items in order to ascertain a "purer" index of hopelessness for this population.
      DESIGN: A cross-sectional study of 200 hospice inpatients with a life expectancy
      of less than 6 months. The HS, as well as several other distress measures, were
      administered to patients at bedside by trained clinicians. METHODS: An item
      analysis of the HS was conducted, looking specifically at item endorsement and
      item-total correlations. Three abbreviated versions (3-item 7-item, 13-item) were
      developed based on certain denoted item-total correlation cut-offs. Reliability
      and validity of the original 20-item HS was then compared to that of the newly
      developed abbreviated version. RESULTS: All scales were found to be reliable and
      valid measures of hopelessness. The three abbreviated versions were more highly
      correlated with the distress measures than the original version, and the 7-item
      and 13-item subscales outperformed the original HS in the prediction of suicidal
      ideation and desire for hastened death. CONCLUSION: The data suggest that the HS
      may be improved, when applied to a terminally ill sample, by the elimination of
      problematic items. The development of a shorter, purer measure of hopelessness
      for this population is crucial given the need to reduce the burden placed on
      those who participate in end-of-life studies, and the important role of
      hopelessness in the prediction of suicide and desire for hastened death.

PMID- 16643693
TI  - Emotions and respiratory function in asthma: a comparison of findings in everyday
      life and laboratory.
AB  - OBJECTIVES: The present study examined the influence of emotions on the
      respiratory function in asthmatic and non-asthmatic individuals in everyday life
      and the relationship to emotion-induced respiratory changes in the laboratory.
      METHODS: Affective states were induced in 10 asthmatic and 10 non-asthmatic
      participants by viewing affective picture series of either a pleasant, neutral,
      or unpleasant valence, while airway resistance (Raw) was measured with whole body
      plethysmography. Following this, individuals measured their mood, forced
      expiratory volume in the first second (FEV1), peak expiratory flow (PEF),
      physical activity, and medication use for 21 days with an electronic diary, which
      included a respiratory self-measurement device. Strong pleasant and unpleasant
      mood episodes were extracted from the diaries and compared with neutral affective
      states. RESULTS: Asthmatic patients showed increases of Raw after unpleasant and
      pleasant emotional stimulation in the laboratory, which was only found after a
      pleasant stimulation in non-asthmatic participants. In everyday life, no group
      differences were obtained. Episodes of strong unpleasant mood states were
      associated with decreases in PEF, whereas in contrast to the laboratory
      assessment, pleasant mood was associated with increases in PEF. Results for FEV1
      were comparable, but non-significant. Physical activity and medication use did
      not vary systematically between affective episodes. PEF showed no significant
      relationship with Raw. CONCLUSIONS: Unpleasant mood is associated with decreased
      respiratory function in asthmatic patients in everyday life and in laboratory
      assessments, whereas effects of pleasant mood states are inconsistent. Pulmonary
      responses to laboratory-induced emotional conditions are not predictive of
      airways reactivity during daily life.

PMID- 16643694
TI  - Illness representations of coronary artery disease: an empirical examination of
      the Illness Perceptions Questionnaire (IPQ) in patients undergoing surgery,
      angioplasty and medication.
AB  - BACKGROUND: This study sought to validate empirically, through factor analysis,
      the theoretically developed Illness Perceptions Questionnaire (IPQ) measure of
      illness representations, and investigated how illness representations varied
      within an illness condition between different treatments. METHODS: Two hundred
      and fourteen coronary artery disease (CAD) patients, 70 of whom were undergoing
      medication, 71 to undergo angioplasty and 73 to undergo coronary artery bypass
      surgery (CABG), completed the New Zealand Heart Attack Recovery Project version
      of the IPQ. The core cognitive illness representation statement responses were
      subject to principal components analyses (PCA), with oblique rotation. Identity
      data were examined regarding symptom frequency. Subscales based on factor
      structures and frequency scores were utilized to investigate treatment group
      differences in illness beliefs through analysis of covariance (ANCOVA). FINDINGS:
      PCA of the core components indicated four factors labelled: 'illness impact',
      'duration', 'control', and 'self-image', accounting for 46.5% of the variance.
      The most frequently experienced symptoms were fatigue, breathlessness and chest
      pain (angina). ANCOVAs showed significant treatment group differences in
      frequency of chest-pain experienced (medication<CABG, p<.01) and differences on
      illness 'duration' beliefs (medication>revascularization groups, p<.001).
      DISCUSSION: The results produced a modified structure for the IPQ, which appeared
      to reflect the nature of the illness under study and the possible fractionation
      of the core illness representation components. Responses on the subscales created
      were also related to the position within the 'subjective experience with the
      illness' that a patient had reached and the treatment being undertaken.

PMID- 16643695
TI  - Genetic testing and the relationship between specific and general self-efficacy.
AB  - The study examined the extent to which variations in health-specific self
      efficacy could affect general self-efficacy. In a repeated measures design, 300
      participants were administered an efficacy questionnaire, before and after an
      alleged news report, aimed at increasing or decreasing self-efficacy over genetic
      testing decision making. The results found that self-efficacy over testing was
      significantly reduced after reading the negative news report in those
      participants who felt personal efficacy over testing decisions was important.
      Levels of general self-efficacy were also significantly decreased. The findings
      suggest that being denied control over a specific area of self-efficacy can have
      a wider impact, with a lack of perceived efficacy over testing decision making
      adversely impacting on levels of general well-being. The wider implications of
      this generalization effect and the processes involved in efficacy generalization
      are discussed.

PMID- 16643696
TI  - Examination of a sociocultural model of disordered eating among male and female
      adolescents.
AB  - OBJECTIVES: The study tests a version of Stice's (1994) sociocultural model of
      disordered eating that was modified to incorporate social comparisons.
      Additionally, it examines how self-reported body-mass index and perceived weight
      status influence associations within the model. METHOD: Questionnaires were
      administered in a state secondary school; the sample consisted of 250 female and
      257 male adolescents aged 11-16 years. RESULTS: The results supported the
      sociocultural model among both male and female adolescents. Perceived pressure to
      lose weight was directly associated with eating behaviour, as well as indirectly
      associated through social comparisons, internalization and body dissatisfaction.
      However, social comparisons were most strongly related to body dissatisfaction
      among adolescents who perceived themselves as overweight. CONCLUSIONS: The
      findings indicate that models of eating disordered behaviour, developed for
      adolescent girls, are also appropriate for understanding this behaviour among
      male adolescents. The results suggest that social comparisons represent a useful
      addition to Stice's (1994) original model and a potentially fruitful target for
      interventions.

PMID- 16643697
TI  - Using past behaviour and spontaneous implementation intentions to enhance the
      utility of the theory of planned behaviour in predicting exercise.
AB  - OBJECTIVES: This study examined the utility of the theory of planned behaviour
      (TPB), past behaviour, and spontaneous implementation intentions in predicting
      exercise behaviour. The psychological correlates of spontaneous implementation
      intentions and the moderating effects of intention, perceived behavioural
      control, past behaviour, and implementation intentions at various time points
      were also examined. DESIGN: Data collection occurred over three phases with a 2-
      and 3-week interval. The attrition rate was 35.97% leaving a total of 162
      participants (63 males, 99 females). In the first wave, participants completed
      measures of TPB, spontaneous implementation intentions, and past behaviour.
      Behaviour was assessed in the second and third waves, and a follow-up measure of
      spontaneous implementation intentions was completed in Phase 3. RESULTS: Several
      regression analyses were conducted. Attitude towards exercise and perceived
      behavioural control made a significant contribution to the prediction of
      intention. Intention made a significant contribution to the prediction of
      implementation intentions. Spontaneous implementation intentions reduced the
      effect of intention and past behaviour for behaviour at 2 weeks and when indexed
      over a 5-week period. When behaviour was measured for a 3-week period (following
      an initial 2-week period), the variance that intention and past behaviour
      accounted for in exercise behaviour decreased, and spontaneous implementation
      intentions were no longer a significant predictor of behaviour. Spontaneous
      implementation intentions were found to interact with past behaviour, such that
      implementation intentions predicted exercise behaviour only among participants
      who did not exercise frequently in the past. CONCLUSIONS: Implications and future
      research directions are discussed.

PMID- 16643698
TI  - A randomized controlled trial of smoking cessation for pregnant women to test the
      effect of a transtheoretical model-based intervention on movement in stage and
      interaction with baseline stage.
AB  - OBJECTIVES: To examine whether, as predicted by the transtheoretical model (TTM),
      stage-matched interventions will be more effective than stage-mismatched
      interventions. DESIGN: Randomized controlled trial of smoking cessation advice to
      pregnant smokers. METHODS: Pregnant women currently smoking at 12 weeks gestation
      were enrolled in a pragmatic three-arm trial of TTM-based interventions to help
      them stop smoking. One arm constituted standard midwifery advice and a self-help
      leaflet on stopping smoking, which is generally appropriate for women in
      preparation. Two arms were TTM-based. Differences in positive movement in stage
      towards quitting from enrolment to 30 weeks gestation and 10 days post-partum
      were calculated for each arm of the trial. We then examined whether, as predicted
      from the TTM, the relative benefit of the TTM-based intervention was greater for
      women in precontemplation and contemplation, for whom the control intervention
      was stage-mismatched, than for women in preparation, for whom the control
      intervention was stage-matched. RESULTS: Women in the TTM-based arms were
      statistically significantly more likely to move forward in stage than were women
      in the control arm. Contrary to the TTM-derived hypothesis, the greater relative
      benefit of the TTM-based intervention was seen for women in preparation stage at
      baseline, rather than women in precontemplation and contemplation. CONCLUSIONS:
      The TTM-based intervention was more effective in stage movement, but this could
      be due to its greater intensity. The failure to confirm that stage-matching was
      important casts doubt on the validity of the TTM in explaining smoking cessation
      behaviour in pregnancy.

PMID- 16643699
TI  - Social and emotional characteristics of adults seeking a cochlear implant and
      their spouses.
AB  - OBJECTIVES: Because past research has shown that benefits of cochlear
      implantation may include a significant decrease in psychological and emotional
      difficulties, this study examined whether persons seeking cochlear implants in
      recent years differed psychologically from those referred in the early 1980s. A
      second objective was to explore mechanisms by which profound deafness could
      contribute to psychological and emotional difficulties for implant candidates and
      their spouses. METHODS: 178 cochlear implant candidates referred from 1981 to
      1998 at the University of Iowa Hospitals completed a standard battery of
      psychological tests and questionnaires. The sample was divided into six 3-year
      cohorts and compared on standardized measures of psychological and emotional
      adjustment, and in participation in social and non-social activities. Spouses of
      implant candidates completed a similar assessment. RESULTS: The sample was
      characterized by elevations in depression, social introversion, suspiciousness,
      and social anxiety and loneliness. There were no significant differences among
      cohorts across time except for an increase in expectations for implant success.
      Spouses also evidenced elevated levels of psychological distress. Hearing status
      was associated with significant differences in social activity participation. A
      paradoxical interaction was found between marital status and deafness.
      CONCLUSIONS: There was no evidence that the psychological status of implant
      candidates is changing across time, suggesting continued psychological benefit
      for persons receiving cochlear implants. Both candidates and their spouses
      participated in fewer social activities than normal controls. Findings underscore
      the complex relation between marital status, deafness, and engagement and
      participation in positive activities.

PMID- 16643700
TI  - Development of a measure of the concerns held by people with implanted
      cardioverter defibrillators: the ICDC.
AB  - OBJECTIVES: To develop a questionnaire to measure the extent and severity of the
      concerns of people with an implanted cardioverter defibrillator. DESIGN: Items
      were generated from patient interviews, expert review and the research literature
      on patients' worries and concerns. A pilot version was administered to a series
      of ICD patients and repeated for test-retest reliability 6 weeks later.
      Psychometric tests including the screen test, factor analysis and various
      reliability assessments were undertaken. It was predicted that the greater the
      extent and severity of concerns, the greater the anxiety experienced by the ICD
      patient. Scores were compared with a validated measure of anxiety and depression
      administered at the same time. RESULTS: Fifty-seven (64%) patients completed and
      returned the questionnaire and a further 22 (100% of those asked) completed the 6
      week retest. Reliability and validity appeared to be good and two factors were
      identified. Both total score and the individual factor scores correlated
      moderately with anxiety. CONCLUSIONS: The questionnaire appears to reflect
      patients' concerns and, as predicted, these were associated with the patients'
      anxiety level. The scale requires further testing to reveal if it is of use both
      clinically and for research purposes.

PMID- 16643701
TI  - Psychological distress and visual functioning in relation to vision-related
      disability in older individuals with cataracts.
AB  - OBJECTIVE: To determine whether demographic, health status and psychological
      functioning measures, in addition to impaired visual acuity, are related to
      vision-related disability. METHODS: Participants were 105 individuals (mean
      age=73.7 years) with cataracts requiring surgery and corrected visual acuity in
      the better eye of 6/24 to 6/36 were recruited from waiting lists at three public
      out-patient ophthalmology clinics. Visual disability was measured with the Visual
      Functioning-14 survey. Visual acuity was assessed using better and worse eye
      logMAR scores and the Melbourne Edge Test (MET) for edge contrast sensitivity.
      Data relating to demographic information, depression, anxiety and stress, health
      care and medication use and numbers of co-morbid conditions were obtained.
      RESULTS: Principal component analysis revealed four meaningful factors that
      accounted for 75% of the variance in visual disability: recreational activities,
      reading and fine work, activities of daily living and driving behaviour. Multiple
      regression analyses determined that visual acuity variables were the only
      significant predictors of overall vision-related functioning and difficulties
      with reading and fine work. For the remaining visual disability domains, non
      visual factors were also significant predictors. Difficulties with recreational
      activities were predicted by stress, as well as worse eye visual acuity, and
      difficulties with activities of daily living were associated with self-reported
      health status, age and depression as well as MET contrast scores. Driving
      behaviour was associated with sex (with fewer women driving), depression, anxiety
      and stress scores, and MET contrast scores. CONCLUSION: Vision-related disability
      is common in older individuals with cataracts. In addition to visual acuity,
      demographic, psychological and health status factors influence the severity of
      vision-related disability, affecting recreational activities, activities of daily
      living and driving.

PMID- 16643702
TI  - A systematic review of motivational interviewing in physical health care
      settings.
AB  - PURPOSE: Motivational interviewing (MI), a method of augmenting an individual's
      motivation to change problematic behaviours, is a patient-centred counselling
      style that seeks to help patients resolve ambivalence about behaviour change. MI
      has successfully been used in the field of addictions and has recently received
      increased interest as a means of promoting treatment adherence in physical health
      care settings. This systematic review is aimed to evaluate the effectiveness of
      MI interventions in physical health care settings. METHODS: Electronic databases
      were searched for articles specifying the use of 'motivational interviewing' in
      physical health care settings between 1966 and April 2004. Fifty-one relevant
      abstracts were yielded and data was extracted from eight relevant selected
      studies. RESULTS: Eight studies were identified in the fields of diabetes,
      asthma, hypertension, hyperlipidaemia, and heart disease. The majority of studies
      found positive results for effects of MI on psychological, physiological, and
      life-style change outcomes. Problems with research in this area include: small
      sample sizes, lack of power, use of disparate multiple outcomes, inadequate
      validation of questionnaires, poorly-defined therapy and training. CONCLUSIONS:
      While MI has high face validity across a number of domains in physical health
      care settings, the general quality of trials in this area is inadequate and
      therefore recommendations for its dissemination in this area cannot yet be made.
      More research into MI applied to health behaviour change is urgently required.

PMID- 16643703
TI  - Does changing the order of threat and efficacy information influence the
      persuasiveness of threat messages?
AB  - OBJECTIVES: The aim of this study is to investigate the impact of changing the
      conventional threat-before-efficacy order of threat messages on the
      persuasiveness of a leaflet informing women smokers of the link between smoking
      and cervical cancer. DESIGN: The study used a between-groups design in which
      women smokers were sequentially allocated to one of three groups. Two groups
      received one of two leaflets aimed at providing information about the link
      between smoking and cervical cancer: one provided threat-before-efficacy
      information; the other provided efficacy-before-threat information. The third
      group received no leaflet. METHODS: Participants (N=178) were recruited by a
      commercial survey organization. Purposeful sampling was used to ensure that women
      with a wide range of ages and educational qualifications were included. Outcomes
      were intention to stop smoking, recall of information, and threat and efficacy
      perceptions. RESULTS: Although women in the 'efficacy-before-threat' group
      recalled more efficacy information, and those in the 'threat-before-efficacy'
      group recalled more threat information, the leaflets were similarly persuasive.
      Compared with women not given a leaflet, those given either of the two leaflets
      had greater intentions to stop smoking and higher threat and efficacy
      perceptions. CONCLUSIONS: Informing women of the link between smoking and
      cervical cancer increases their intentions to stop smoking. Changing the order of
      threat and efficacy information does not influence the persuasiveness of this
      message. Order effects may be more likely in experimental contexts using weaker
      messages or those that are not novel.

PMID- 16643704
TI  - A multi-level decomposition of variance in somatic symptom reporting in families
      with adolescent children.
AB  - OBJECTIVES: This paper examines four different levels of possible variation in
      symptom reporting: occasion, day, person and family. DESIGN: In order to rule out
      effects of retrospection, concurrent symptom reporting was assessed prospectively
      using a computer-assisted self-report method. METHODS: A decomposition of
      variance in symptom reporting was conducted using diary data from families with
      adolescent children. We used palmtop computers to assess concurrent somatic
      complaints from parents and children six times a day for seven consecutive days.
      In two separate studies, 314 and 254 participants from 96 and 77 families,
      respectively, participated. A generalized multilevel linear models approach was
      used to analyze the data. Symptom reports were modelled using a logistic response
      function, and random effects were allowed at the family, person and day level,
      with extra-binomial variation allowed for on the occasion level. RESULTS:
      Substantial variability was observed at the person, day and occasion level but
      not at the family level. CONCLUSIONS: To explain symptom reporting in normally
      healthy individuals, situational as well as person characteristics should be
      taken into account. Family characteristics, however, would not help to clarify
      symptom reporting in all family members.

PMID- 16643705
TI  - The productive performance of public hospital clinics in Greece: a case study.
AB  - One of the most important and crucial issues for political and social reasons in
      Greece is the reorganization of the public sector health system--more precisely,
      the improvement of public hospital operations, both in terms of the resources
      they use and the quality and quantity of the services they provide. This study
      focuses on investigating the productivity performance of 10 clinics in a public
      hospital located in Thessaloniki. The methodology applied is the data envelopment
      analysis (DEA) to measure the Malmquist productivity index. The results indicated
      that the efficiency of the hospital clinics has improved. However, clinics'
      efficiency varies a lot from month to month. In a competitive environment, these
      differences need to be addressed, investigated and reduced in order to improve
      total efficiency.

PMID- 16643706
TI  - Building IT capability in health-care organizations.
AB  - While computer technology has revolutionized industries such as banking and
      airlines, it has done little for health care so far. Most of the health-care
      organizations continue the early-computer-era practice of buying the latest
      technology without knowing how it might effectively be employed in achieving
      business goals. By investing merely in information technology (IT) rather than in
      IT capabilities they acquire IT components--primarily hardware, software, and
      vendor-provided services--which they do not understand and, as a result, are not
      capable of fully utilizing for achieving organizational objectives. In the
      absence of internal IT capabilities, health-care organizations have relied
      heavily on the fragmented IT vendor market in which vendors do not offer an open
      architecture, and are unwilling to offer electronic interfaces that would make
      their 'closed' systems compatible with those of other vendors. They are hamstrung
      as a result because they have implemented so many different technologies and
      databases that information stays in silos. Health systems can meet this challenge
      by developing internal IT capabilities that would allow them to seamlessly
      integrate clinical and business IT systems and develop innovative uses of IT.
      This paper develops a comprehensive conception of IT capability grounded in the
      resource-based theory of the firm as a remedy to the woes of IT investments in
      health care.

PMID- 16643707
TI  - The costs and service implications of substituting intermediate care for acute
      hospital care.
AB  - Intermediate care is part of a package of initiatives introduced by the UK
      Government mainly to relieve pressure on acute hospital beds and reduce delayed
      discharge (bed blocking). Intermediate care involves caring for patients in a
      range of settings, such as in the home or community or in nursing and residential
      homes. This paper considers the scope of intermediate care and its role in
      relation to acute hospital services. In particular, it develops a framework that
      can be used to inform decisions about the most cost-effective care pathways for
      given clinical situations, and also for wider planning purposes. It does this by
      providing a model for evaluating the costs of intermediate care services provided
      by different agencies and techniques for calibrating the model locally. It finds
      that consistent application of the techniques over a period of time, coupled with
      sound planning and accounting, should result in savings to the health economy.

PMID- 16643708
TI  - Developing the electronic health record: what about patient safety?
AB  - This paper examines the development of electronic health records within the
      National Health Service (NHS) by an analysis of a series of pilot projects funded
      by the Electronic Record Development and Implementation Project (ERDIP), one
      aspect of the work of the NHS Information Authority (NHSIA) (As of 1 April 2005,
      the NHSIA ceased to operate. Much of its work is continued by Connecting for
      Health and the Health and Social Care Information Centre.) The focus of the
      analysis is on the extent to which identifying and correcting error within health
      records was explored through these projects. The inherent potential for error and
      resultant impact on patient safety is highlighted, by considering the context of
      the record, the content of the record and the process of change from paper-based
      or piecemeal electronic health records to integrated electronic health records.
      While the process of change highlights issues of data security and access, it is
      the variability in starting points for different organizations that possibly
      poses most risk to patient safety. Issues relating to the content of the record
      can to some extent be minimized by the effective use of technology, but the
      tension between coding and qualitative data requires further consideration in
      terms of its impact on patient safety. This paper concludes that the development
      of electronic health records has to be viewed within the context of governance
      and patient safety, and the implications articulated.

PMID- 16643709
TI  - Clinical leaders at the forefront of change in health-care systems: advantages
      and issues. Lessons learned from the evaluation of the implementation of an
      integrated oncological services network.
AB  - Based on lessons learned from the evaluation of the implementation of an
      integrated oncological services network in Quebec, this paper discusses the
      following question: to what extent is strong clinical leadership a propitious
      means of transforming health-care systems, especially when the change leads to
      significant evolution in inter-professional and inter-organizational relations?
      Through a qualitative case study, we analysed the exercising of leadership by
      studying over time the clinical leaders' initiatives while trying to understand
      the sources of influence, the nature of the tactics adopted and their
      consequences for the degree of integration of health services. This study seems
      to show that clinical leadership is effective but limited. We conclude that a
      constellation of clinical, administrative and political leaders found at
      different levels of the health-care system offers more promise of positive change
      for the health-care system.

PMID- 16643710
TI  - Hospital responses to pay-for-performance incentives.
AB  - Not-for-profit hospitals are complex organizations and, therefore, may face
      unique challenges in responding to financial incentives for quality. In this
      research, we explore the types of behavioural changes made by not-for-profit
      Michigan hospitals in response to a pay-for-performance system for quality. We
      also identify factors that motivate or facilitate changes in effort. We apply a
      conceptual framework based on agency theory to motivate our research questions.
      Using data derived from structured interviews and surveys administered to 86
      hospitals participating in a pay-for-performance system, we compare hospitals
      reporting and not reporting behavioural changes. Separate analyses are performed
      for hospitals reporting structure-related changes and hospitals reporting process
      related changes. Our findings confirm that hospitals respond to incentive
      payments; however, our findings also reveal that hospital responses are not
      universal. Rather, involvement by boards of trustees, willingness to exert
      leverage with physicians, and financial and competitive motivations are all
      associated with hospitals' behavioural responses to incentives. Results of this
      research will help inform payers and hospital managers considering the use of
      incentives about the nature of hospitals' responses.

PMID- 16643711
TI  - Musings about medical school: could I get in today?

PMID- 16643712
TI  - Compassion as well as clarity.

PMID- 16643713
TI  - Gestational diabetes mellitus outcome in 394 patients.
AB  - OBJECTIVE: To determine whether women with gestational diabetes mellitus (GDM)
      and their offspring have pregnancy outcomes and complications of pregnancy that
      are different from those in the general obstetric population. METHODS: Through
      medical record coding, we identified women with GDM and a singleton pregnancy
      with cephalic presentation who delivered at St. Paul's Hospital between January
      1, 1995, and December 31, 2001. In total, 394 births were analyzed and their
      outcomes compared with those of a control group of 100 non-diabetic women with
      the same gestational age (38 weeks) at delivery. RESULTS: Women with gestational
      diabetes were of lesser parity (P 0.05), appreciably older (P 0.05), and less
      likely to be Caucasian (P 0.005) than the general obstetric population. Women
      with GDM also had a higher risk of Caesarean section (P 0.05), gestational
      hypertension (P 0.05), and large for gestational age (LGA) deliveries (P 0.005).
      Of women with GDM, those treated with insulin had a higher incidence of LGA
      deliveries than those on diet therapy alone. The incidence of respiratory
      distress syndrome and of need for phototherapy was similar in babies whose
      mothers had GDM and in those whose mothers did not. CONCLUSION: Although the rate
      of complications remains low, GDM creates a predisposition to increased maternal
      and neonatal complications.

PMID- 16643714
TI  - Hamman's syndrome (spontaneous pneumomediastinum) in a parturient: a case report.
AB  - BACKGROUND: Subcutaneous emphysema and pneumomediastinum in labour and delivery
      is a rare but potentially serious occurrence that must be identified and managed
      appropriately to avoid unnecessary investigations and interventions. Published
      reports indicate that subsequent pregnancies pose no additional risk for
      recurrence. CASE: A 27-year-old primiparous patient with an uneventful pregnancy
      and delivery developed subcutaneous emphysema but remained stable clinically.
      Chest radiography confirmed a pneumomediastinum. She was managed conservatively
      with supportive measures and anxiolytics and showed complete resolution after
      five days. A future pregnancy is planned. CONCLUSION: Recognition of spontaneous
      pneumomediastinum and its potential consequences during labour and delivery
      requires vigilance. Supportive measures alone may be the only requirement for
      resolution. Recurrence of the condition is rare, but the appropriate management
      of subsequent pregnancies is unclear. Expectant management with epidural
      analgesia to minimize active pushing is suggested in a subsequent spontaneous
      vaginal delivery.

PMID- 16643715
TI  - Minimizing the urological and psychological morbidity of urinary tract fistulae
      from VBAC.
AB  - BACKGROUND: Because of the relative rarity of the condition, there is no
      consensus for the timing of surgical repair of fistulae following vaginal birth
      after Caesarean section (VBAC). CASES: Three cases of urinary tract fistulae
      following VBAC are presented. Two patients had an early repair (24-48 hours after
      delivery), and the third had a repair at four months after delivery. The surgical
      approach and intraoperative findings for the early and late repairs are
      described, and the psychological effects of early and late repair are compared.
      The early repairs were not technically difficult and were associated with less
      psychological morbidity. CONCLUSION: In the absence of contraindications, early
      repair of urinary tract fistulae diagnosed within the first few days after VBAC
      delivery is preferred. If early repair is attempted, perioperative conditions
      must be optimized; urogynaecologic or urologic expertise and assistance should be
      considered.

PMID- 16643716
TI  - Anabolic agents: a new chapter in the management of osteoporosis.
AB  - Osteoporosis in postmenopausal women has until now been treated with
      antiresorptive agents, reducing the incidence of fragility fracture by
      approximately 50%. Clinical research has led to the development of new anabolic
      therapies capable of increasing the production of bone matrix by osteoblasts and
      reversing microarchitectural deterioration, resulting in major improvements in
      both bone quality and bone quantity. Teriparatide, a recombinant human
      parathyroid hormone consisting of the first 34 of 84 amino acids in human
      parathyroid hormone, has been shown to reduce significantly the risk of both
      vertebral and non-vertebral fractures in postmenopausal women. This agent was
      recently approved for use in Canada. Strontium ranelate is a new oral agent
      capable of uncoupling bone resorption from bone formation, which results in
      increases in bone formation with reductions in bone resorption. This agent has
      also been shown to reduce the risk of both vertebral and non-vertebral fracture
      while improving bone structure. Anabolic therapies represent a major advance in
      the management of postmenopausal osteoporosis, and they may provide significant
      benefit to those patients with severe osteoporosis in whom antiresorptive therapy
      has proven insufficient. Anabolic therapies should complement the antiresorptive
      treatments currently available for use in women with postmenopausal osteoporosis.

PMID- 16643717
TI  - Early abortion in Ontario: options and costs.
AB  - OBJECTIVE: Early abortions have been predominantly surgical for many years, but
      medical options with comparable efficacy and safety are now available. This study
      compares the costs of two medical options and two surgical options. METHODS: We
      used a clinical model to compare the costs in Ontario of four options for early
      abortion: medical abortion using either mifepristone or methotrexate, and
      surgical abortion by vacuum aspiration in either a hospital or a free-standing
      clinic. The cost analysis was conducted from the perspectives of society, the
      health care system, and the patient. RESULTS: From all perspectives, total costs
      were highest for hospital surgical abortion, followed by surgical abortion in a
      clinic. From the patient's perspective, total costs were higher for surgical
      abortion but direct costs (mainly for medications) were higher for medical
      abortion. The total cost of mifepristone and methotrexate abortion was equal if
      the price of mifepristone (200 mg) was $59.52. The model was robust but was
      sensitive to the price of mifepristone. CONCLUSION: Early medical abortion costs
      less than early surgical abortion from the societal and health care system
      perspectives but more than surgical abortion from the patient's perspective.
      Surgical abortion costs more in hospitals than in free-standing clinics from the
      societal and health care system perspectives, but the costs are the same in both
      settings from the patient's perspective. No method for early abortion can be
      identified as best, and patients should be free to choose the option they prefer.

PMID- 16643718
TI  - Factors that influence length of stay for in-patient gynaecology surgery: is the
      Case Mix Group (CMG) or type of procedure more important?
AB  - OBJECTIVES: To compare the association between the Case Mix Group (CMG) code and
      length of stay (LOS) with the association between the type of procedure and LOS
      in patients admitted for gynaecology surgery. METHODS: We examined the records of
      women admitted for surgery in CMG 579 (major uterine/adnexal procedure, no
      malignancy) or 577 (major surgery ovary/adnexa with malignancy) between April
      1997 and March 1999. Factors thought to influence LOS included age, weight,
      American Society of Anesthesiologists (ASA) score, physician, day of the week on
      which surgery was performed, and procedure type. Procedures were divided into six
      categories, four for CMG 579 and two for CMG 577. Data were abstracted from the
      hospital information costing system (T2 system) and by retrospective chart
      review. Multivariable analysis was performed using linear regression with
      backwards elimination. RESULTS: There were 606 patients in CMG 579 and 101
      patients in CMG 577, and the corresponding median LOS was four days (range 1-19)
      for CMG 579 and nine days (range 3-30) for CMG 577. Combined analysis of both
      CMGs 577 and 579 revealed the following factors as highly significant
      determinants of LOS: procedure, age, physician, and ASA score. Although
      confounded by procedure type, the CMG did not significantly account for
      differences in LOS in the model if procedure was considered. Pairwise comparisons
      of procedure categories were all found to be statistically significant, even when
      controlled for other important variables. CONCLUSION: The type of procedure
      better accounts for differences in LOS by describing six statistically distinct
      procedure groups rather than the traditional two CMGs. It is reasonable therefore
      to consider changing the current CMG codes for gynaecology to a classification
      based on the type of procedure.

PMID- 16643719
TI  - Fertility and pregnancy outcomes following hysteroscopic septum division.
AB  - OBJECTIVES: We sought to evaluate retrospectively the efficacy of hysteroscopic
      metroplasty in a population of women with a history of recurrent pregnancy loss
      or infertility who were also known to have a uterine septum. METHODS:
      Hysteroscopic metroplasty was performed on 26 women with a uterine septum and a
      history of either recurrent pregnancy loss or infertility. The metroplasty was
      performed using a Versapoint bipolar needle device (in 23% of cases) or a
      resectoscopic knife electrode with cutting current (in 77% of cases). The main
      outcome measures were rates of clinical pregnancy and live birth. RESULTS:
      Nineteen women had a hysteroscopic metroplasty because of recurrent pregnancy
      loss. Postoperatively, the pregnancy rate was 95%, and the live birth rate was
      72%. The seven infertile patients had pregnancy and live birth rates of 43% and
      29%, respectively. CONCLUSION: Hysteroscopic metroplasty using either the
      Versapoint bipolar needle device or a knife electrode is both safe and effective.
      In women with recurrent pregnancy loss, future fertility is not impaired, and
      live birth rates are significantly improved.

PMID- 16643720
TI  - Vesicovaginal fistula with bladder eversion: a rare complication of third degree
      cervical descent.

PMID- 16643721
TI  - [Emphasis on the research of apoptosis in retinal degeneration diseases].
AB  - Many ocular fundus diseases such as retinitis pigmentosa and age-related macular
      degeneration are retinal degeneration diseases, which may lead to visual loss.
      The main pathologic character of such retinal degeneration diseases is apoptosis
      of retinal cells. In recent years, some progresses have been achieved on the
      prevention of apoptosis of retinal cells. In the field of ophthalmologic clinical
      and basic research, it is important to explore the use of anti-apoptotic
      approaches as novel preventive and therapeutic procedures for retinal
      degeneration diseases.

PMID- 16643722
TI  - [Guidance of regenerative axons in optic nerve regeneration in Bcl-2
      overexpressing mice].
AB  - OBJECTIVE: To determine whether optic nerve can regenerate after optic nerve
      crush and weather the regenerating axon reaches the target in the brain in Bcl-2
      overexpressing mice. METHODS: Left eye optic nerve crush was performed in wild
      type (C57Bl/6J) and Bcl-2 transgenic mouse pups at 3 days after birth (P3),
      followed immediately by the opposite eyeball enucleated. Mouse pups were killed
      at 4 days post-surgery. Optic nerve regeneration was assessed at the sections of
      optic nerve and the brain. An anterograde tracer, cholera toxin B subunit
      conjugated with fluorescein (CTB-F), was applied intraocularly, immediately after
      optic nerve crush to label retinal ganglion cell axons. Immunofluorescence
      staining with anti-GAP-43 was carried out to reveal regenerating axons in optic
      nerve sections. RESULTS: In wild-type mice, severed optic nerves failed to
      regenerate. In contrast, in all of the Bcl-2 transgenic mice examined, optic
      nerves regenerated robustly over long distances, but the regenerating fibers were
      found to deviate from the optic pathway and grew into the forebrain to form
      aberrant projection. CONCLUSION: When the opposite eyeball is removed in P3 Bcl-2
      overexpressing mice with optic nerve was crushed in one side, the guidance from
      the normal optic pathway is lost, the optic nerve could regenerate and reach the
      brain, but the regenerating axons could not reach both side of target in the
      midbrain, they grow into aberrant place of forebrain.

PMID- 16643723
TI  - [Isolation, culture and identification of rat retinal progenitor cells in vitro].
AB  - OBJECTIVE: To characterize embryonic rat retinal progenitor cells (RPCs) by flow
      cytometry (FACS), immunofluorescence and (3)H-Thymidine assay in vitro. METHODS:
      RPCs were prepared from the retina of embryonic day 19 Sprague Dawley rats and
      were cultured in DMEM: F12 medium with N2-supplement, epidermal growth factor
      (EGF), basic fibroblast growth factor (bFGF) and leukemia inhibitory factor (LIF)
      for 0 to 4 days. Cell proliferation and cluster formation were quantified by (3)H
      Thymidine assay and morphometric analysis, respectively. Antibodies used to
      characterize the RPCs included markers for neural progenitors (Nestin and Sox-2),
      astrocytes (glial fibrillary acidic protein [GFAP]), horizontal cells
      (Calretinin), ganglion cells (CD90), rods (Rhodopsin), biopolar cells (PKC) and
      amacrine cells (Syntaxin) by the use of FACS. RESULTS: In primary cells, 22.23%,
      16.04% and 19.66% of cells were found to express Nestin, Sox-2 and Calretinin,
      respectively. GFAP, CD90, Rhodopsin, PKC, Syntaxin were not detected or trail.
      Meanwhile, more than 90% cells were Nestin positive by immunofluorescence. After
      6 days culture in vitro, 43.36% cells express Nestin by FACS. Nestin and GFAP
      were expressed by use of immunofluorescence. There was significant proliferation
      of RPCs within the first 4 days as evaluated by (3)H-Thymidine assay.
      CONCLUSIONS: The results demonstrate that combine FACS, immunofluorescence and
      (3)H-Thymidine assay together could characterize RPCs. RPCs proliferate well at
      the early period of cell culture.

PMID- 16643724
TI  - [Transfer of endostatin gene for inhibition of retinal angiogenesis in mice].
AB  - OBJECTIVE: To evaluate the effect of liposome mediated plasmids encoding
      endostatin (ES) injected into the vitreous to inhibit experimental retinal
      neovascularization. METHODS: Cationic liposome mediated ES expression plasmid
      PCDNA(3)-ES was constructed. One-week-old C57Bl/6N mice were exposed to (75 +/-
      2)% oxygen for 5 days, then returned to the room air to induce retinal
      neovascularization. Cationic liposome mediated ES complex (2 microl) was injected
      into the vitreous in the treatment group. PBS 2 microl or liposome with carrier
      DNA complex were injected in the control group. The ES protein expression in the
      retina was tested with immunohistological methods at 1, 3, 7 and 14 days after
      injection. Retinal neovascularization was evaluated by angiography with injection
      of fluorescein dextran and quantification of neovascular proliferative
      retinopathy after 5 days in room air. To examine the toxicity of the liposome and
      plasmid PCDNA(3)-ES complex, the histological changes in the retina were examined
      by light and electron microscopy. RESULTS: ES protein was expressed in the retina
      24 hours after injection. Most of them presented in the retinal ganglion layer.
      This could last for 2 weeks at least. Retina of the PBS-injected eyes of retinal
      neovascular animal model showed prominent neovascular tuft and fluorescein
      leakage. Fewer neovascular tufts could be seen after ES injection. Retinal
      neovascularization in the eyes injected with ES plasmids complex was reduced as
      compared with the control group. No side effect on the retina was observed by
      light and electron microscopy. CONCLUSIONS: Liposome mediated plasmids encoding
      ES can be transferred to retinal cells by vitreous injection and can suppress
      retinal neovascularization, no side or toxic effects are presented in the retina.
      Further studies should be done to improve the treatment results.

PMID- 16643725
TI  - [Gene regulatory mechanism of hairy and enhancer of split related-1 for
      angiogenesis factors].
AB  - OBJECTIVE: To study the roles of hairy and enhancer of split related-1 (HESR-1)
      in maintenance of the mature, quiescent vessel and angiogenesis. METHODS: Human
      umbilical vein endothelial cells (HUVEC) were cultured. The full-length coding
      sequence of HESR-1 was cloned into PcDNA3.1 + using standard protocols. HESR-1
      specific siRNA was synthesized and cloned into the RNAi-Ready pSIREN-RetroQ
      ZsGreen Vector. The constructed PcDNA3.1 + HESR-1 plasmid were transfected into
      HUVEC for the overexpression of HESR-1, and HESR-1-RNAi plasmid were transfected
      into HUVEC to silence the HESR-1 gene, the expression of KDR, ALK-1 and Ang-1 in
      HUVEC were analyzed by RT-PCR and Western blot. RESULTS: The expression of KDR
      was down-regulated and ALK-1 and Ang-1 were up-regulated in HUVEC with the
      overexpression of HESR-1; The expression of KDR was up-regulated and ALK-1 and
      Ang-1 were down-regulated the HESR-1 in HUVEC by RNAi. CONCLUSION: HESR-1 may
      play an important role in maintenance of vessel in quiescent and control
      angiogenesis by the regulation of the expression of KDR, ALK-1 and Ang-1.

PMID- 16643726
TI  - [Cytoskeleton changes of cultured human retinal pigment epithelial cells in a
      mechanical stress model].
AB  - OBJECTIVE: To observe changes of the cytoskeleton of cultured human retinal
      pigment epithelium (hRPE) cells in a mechanical stress model in vitro. METHODS:
      Ferric oxide beads, coated with collagen, were added to dishes containing
      substrate-attached hRPE cells. After incubation, the cells were washed to remove
      unbound beads. The cells were pretreated by actin polymerization inhibitor
      cytochalasin D (0.05 mmol/L, 25 min). Before and 4, 8, 12 and 24 h after vertical
      magnetic force application the cells were stained for actin and vimentin using
      immunity fluorescence double labelled technique and analyzed with confocal
      microscopy. RESULTS: Four hours after force application, the polarity of hRPE
      cells was changed, and actin was polymerized into filaments in array of them
      along with the direction of the force. Cytoskeleton filaments were located mainly
      around the nucleus and the ferric oxide beads. Pretreatment with cytochalasin D,
      the same changes as described above occurred 8 h after magnetic force
      application. CONCLUSIONS: Mechanical force could induce changes of distribution
      of cytoskeleton in hRPE cells, which are some biological characteristics of
      muscle cells, and this may facilitate the cellular migration and proliferation.

PMID- 16643727
TI  - [Subretinal transplantation of human fetal lung fibroblasts expressed ciliary
      neurotrophic factor gene prevent photoreceptor degeneration in RCS rats].
AB  - OBJECTIVE: To investigate the efficacy of subretinal transplantation of CNTF gene
      transfected fibroblasts for preventing photoreceptor degeneration in RCS.
      METHODS: The human fetal lung fibroblasts with high level expression of CNTF were
      established by liposome mediated gene transfer and MTX selection. A 5 microl of
      cell suspension, containing 1 x 10(5) cells, was injected through pars plana of
      ciliary body into the subretinal space of the right eye at postnatal 4-5 weeks,
      the left eye was left without injection or injected with PBS as controls. The
      both eyes were enucleated for histopathological examinations at 2, 4, 6, 8, 10,
      12 and 15 weeks following transplantation. RESULTS: The level of CNTF protein
      (91,046.15 pg/ml) expressed in the transfected cells was determined by sandwich
      enzyme-linked immunosorbent assay (ELISA). The four of seven eyes examined by
      light microscopy and the ten of 14 eyes examined by electro microscopy showed
      rescue effect. The prolonged photoreceptor survival, reduction of apoptotic cells
      and debris were observed in transplanted eyes in comparison with untreated or
      sham-injected eyes. CONCLUSION: This study provides the first indication that
      transplanted human fibroblasts with high level expression of CNTF are able to
      rescue photoreceptor degeneration in RCS dystrophic rat retina.

PMID- 16643728
TI  - [Changes of reactive oxygen species in mitochondria of retinal endothelial cells
      and pericytes induced by high glucose].
AB  - OBJECTIVE: To study changes of reactive oxygen species (ROS) in mitochondria of
      bovine retinal endothelial cells and pericytes cultured in high-glucose and its
      relevance with the pathogenesis of diabetic retinopathy. METHODS: Bovine retinal
      endothelial cells and pericytes were cultured with selective culture media. ROS
      changes in mitochondria of retinal endothelial cells and pericytes in response to
      different concentrations of glucose were detected with scanning laser confocal
      microscope. The mitochondria membrane potential (MMP) and cell death ratio (CDR)
      were measured with flow cytometry. Expression of MnSOD and uncoupling protein
      (UCP) were detected with reverse-transcriptase PCR (RT-PCR). RESULTS: In high
      glucose, increased ROS was seen in mitochondria of retinal endothelial cells and
      pericytes. However MMP and CDR only increased in endothelial cells, no change was
      found in pericytes. UCP1, 2 mRNA expressed in cultured cells whereas UCP3 was
      negative. The expression of UCP1, 2, MnSOD mRNA changed with the variation of
      glucose concentrations. CONCLUSIONS: Increasing of ROS production in mitochondria
      of retinal endothelial cells and pericytes can be induced by high glucose. There
      is feedback accommodation mechanism between ROS increasing and MMP elevation in
      endothelial cells. The different features of endothelial cells and pericytes in
      high glucose demonstrate their roles in pathogenesis of diabetic retinopathy are
      different.

PMID- 16643729
TI  - [Clinical study on crossed disparity and uncrossed disparity in intermittent
      exotropia before and after surgery].
AB  - OBJECTIVE: To understand the clinical variety of zero disparity, crossed
      disparity and uncrossed disparity in intermittent exotropia before and after
      strabismus surgery. METHODS: 100 cases of intermittent exotropia were involved in
      the study. Before and after surgery, zero disparity stereo-acuity, crossed
      disparity and uncrossed disparity stereo-acuity were examined with stereogram
      designed by Yan Shaoming, distance fusion range and distance stereo-acuity were
      examined with traditional and random dot synoptophore stereogram. The patients
      were divided into four groups based on the results of the stereogram examination
      before surgery. RESULTS: In the 100 cases, there was no coexistence of zero
      disparity and uncrossed disparity, no coexistence of crossed and uncrossed
      disparity, and no existence of only crossed disparity or only uncrossed
      disparity. Postoperative zero disparity, crossed disparity, uncrossed disparity,
      distance fusion range and distance stereo-acuity improved significantly compared
      with the preoperative results for each group (P < 0.01). The comparison of
      distance fusion range was not prominent before and after strabismus surgery in
      the 4 groups (P > 0.05). The distribution of distance stereo-acuity was prominent
      after strabismus surgery in the 4 groups (P < 0.01). Distance stereo-acuity
      rebuilding after surgery in group 1 and group 2 was better than that in group 3
      and group 4. CONCLUSIONS: (1) In the cases with intermittent exotropia, zero
      disparity stereo-acuity, crossed disparity and uncrossed disparity stereo-acuity
      are abnormal. The sequential damage of stereopsis is uncrossed disparity, crossed
      disparity and zero disparity. The sequential rebuilding of stereopsis is zero
      disparity, crossed disparity and uncrossed disparity. (2) The serious damage or
      disappearance of uncrossed disparity stereo-acuity is the indication of
      intermittent exotropia surgery for perfect binocular vision rebuilding.

PMID- 16643730
TI  - [Implantation of phakic anterior chamber intraocular lens for the correction of
      severe myopia].
AB  - OBJECTIVE: To evaluate the efficacy, safety, and predictability of the
      implantation of phakic anterior chamber intraocular lens (PAC-IOL) for the
      correction of severe myopia. METHODS: In this prospective study, 15 cases (29
      eyes) with myopia at -15.00 - -24.50 dioperts (D) were implanted with Phakic
      6H(2) PAC-IOL. Visual acuity, refraction, intraocular pressure, corneal
      endothelium, the PAC-IOL position, contrast sensitivity, glare sensitivity,
      operative complications and poor visual symptoms were observed. RESULTS:
      Postoperative uncorrected visual acuity 0.5 or better was presented in 79.3% eyes
      (23/29) at 3 months and in 82.6% eyes (24/29) at 6 months. Best corrected visual
      acuity 0.8 or better was presented in 69.0 % eyes (20/29) at 3 months and in
      69.0% eyes (20/29) at 6 months, they were all significantly better than that of
      preoperative values (P < 0.05); and there was no statistically significant
      difference between visual acuity at 3 months and 6 months (P > 0.05). Compared
      with preoperative best corrected visual acuity, postoperative uncorrected visual
      acuity improved 2 lines or more in 70.0% of eyes (20/29) at 3 months and 72.4%
      eyes (21/29) at 6 months. The mean postoperative spherical equivalent refraction
      was -1.00D at 3 months, -1.00D at 6 months, they were significantly lower than
      that of preoperative values (P < 0.05); and there was no statistically
      significant difference of spherical equivalent refraction between 3 months and 6
      months (P > 0.05). There were no statistically significant difference between pre
      and post-operative mean intraocular pressure, corneal endothelial density (P >
      0.05) at 3 and 6 months. There was no significant difference of these data
      between 3 months and 6 months (P > 0.05). The PAC-IOL was located (2.341 +/-
      0.116) behind the central cornea, (0.841 +/- 0.140) mm in front of the
      crystalline lens. The footplates appeared to be correctly positioned in the
      anterior chamber angle in all eyes. Contrast sensitivity and glare sensitivity in
      all spatial frequencies increased at 6 months post-operatively as compared with
      those of preoperative values (best spectacle-corrected) (P < 0.05). Postoperative
      complications included a slight inflammatory deposits on the PAC-IOL surface at 3
      months in 10.3% eyes (3/29) and 6.9% eyes (2/29) at 6 months; oval pupil in 10.3%
      eyes (3/29); PAC-IOL rotation in 27.6% eyes (8/29); night glare in 17.2% eyes
      (5/29); all of the other patients were satisfied. CONCLUSIONS: PAC-IOL
      implantation for the correction of severe myopia is effective, safe and
      predictable. It can be a supplement for corneal refractive surgery, but follow-up
      is still required for the evaluation of long-term results.

PMID- 16643731
TI  - [The volume and dimensions of eyeball analyzed by MRI following encircling
      scleral buckles].
AB  - OBJECTIVE: To assess the changes of the volume and dimensions of the eyeball and
      the vitreous following encircling scleral buckle. METHODS: 26 eyes from 26
      patients received successful broad-band encircling scleral buckles for
      rhegmatogenous retinal detachment from July 2002 to December 2003. The
      examinations, A-scan ultrasonography (SONOMED A-5500, USA), Corneal topography
      and MRI, were performed preoperatively and at the first week postoperatively. The
      volume of the eyeballs and the dimensions along the three cardinal axes from 13
      eyeballs were measured with Gyroscan MR imaging system. RESULTS: The measurement
      of MRI for the 13 eyes operated with the encircling scleral buckling revealed
      that the volume of the eyeball was decreased (1.72 +/- 0.49) ml, and volume of
      vitreous was decreased (1.73 +/- 0.46) ml in the comparison with volume before
      surgery. Horizontal and vertical dimensions of eyeball were decreased (7.84 +/-
      1.86) mm, (7.70 +/- 2.79) mm respectively. The length of circumference was
      decreased to (24.42 +/- 6.68) mm, the percentage of the decrease was (33.11 +/-
      8.69)%. The average high of the buckle indentions was (3.80 +/- 0.58) mm with the
      average width of (3.82 +/- 0.60) mm in the temperal part and (3.51 +/- 0.76) mm
      in the nasal part. CONCLUSIONS: The length of the circumference at the site of
      buckling is shorted, and the volume of the vitreous was decreased after the
      surgery. The technique of MRI has an important role in the measurement and
      analysis of the volume and the dimension of the eyeball.

PMID- 16643732
TI  - [Gene and protein expression of thyrotropin-receptor in retro-bulbar tissue from
      thyroid-associated ophthalmopathy].
AB  - OBJECTIVE: To investigate gene and protein expression level of thyrotropin
      receptor (TSHR) in retro-bulbar connective tissue and fat tissue in patients with
      thyroid-associated ophthalmopathy (TAO). METHODS: Retro-bulbar tissues specimens
      were obtained from 11 cases of TAO patients and 10 control cases during the
      operation. RNA was extracted from the tissue specimens using single-step method
      of acid guanidinium-thiocyanate-phenol-chloroform extraction and TSHR mRNA was
      analyzed by reverse transcription polymerase chain reaction (RT-PCR).
      Immunochemistry staining was performed in patients expressed TSHR, using a mouse
      polyclonal anti-TSHR peptide antibody to observe protein expression level of
      TSHR. RESULTS: The size of TSHR mRNA segment is 521 bp. The rate of TSHR mRNA
      expression in TAO retro-bulbar tissue was 91% and was 20% in the control cases,
      the former was significantly greater than the later. Protein expression rate was
      66.7% in TAO patients, and was negative in the controls. CONCLUSIONS: High TSHR
      mRNA expression level and protein level in TAO retro-bulbar tissue and no
      expression in control tissue indicate that TSHR exists as a common antigen in the
      orbit and thyroid, and plays a key role in the pathogenesis of TAO.

PMID- 16643733
TI  - [Changes of tear film after recovery from acute conjunctivitis].
AB  - OBJECTIVE: To investigate tear film changes after recovery from acute
      conjunctivitis. METHODS: This study involved 73 eyes of 56 consecutive patients
      who had recovered from acute conjunctivitis after routine treatment in Zhongshan
      Ophthalmic Center between July 2002 and August 2003. Excluded other factors which
      could affect the stability of the tear film, tear film break up time (BUT),
      Schirmer I test (ST), fluorescein staining (FL) and the height of tear meniscus
      were measured on both recovered and healthy eyes of the patients at 3, 7, 14, 21
      and 30 days after recovery. RESULTS: BUT was 14.72 s in healthy eyes, 5.23, 5.11,
      7.84, 10.26 and 12.74 s in recovered eyes at 3, 7, 14, 21 and 30 days (P = 0.012,
      0.018, 0.032, 0.028 and 0.122), respectively. FL scored at 2.26 in healthy eyes,
      3.02, 6.23, 7.92, 6.37 and 3.53 at 3, 7, 14, 21 and 30 days in recovered eyes (P
      = 0.063, 0.017, 0.008, 0.024 and 0.074), respectively. ST scored at 16.30 mm in
      healthy eyes, 9.39, 11.48, 13.85, 21.24 and 17.40 mm, at 3, 7, 14, 21 and 30 days
      in recovered eyes (P = 0.025, 0.040, 0.082, 0.012 and 0.104), respectively. The
      height of tear meniscus was 0.62 mm in healthy eyes; it scored at 0.39, 0.32,
      0.44, 0.53 and 0.58 mm at 3, 7, 14, 21 and 30 days in recovered eyes (P = 0.008,
      0.015, 0.037, 0.120 and 0.182), respectively. CONCLUSIONS: Instability of tear
      film and transient dry eye can occur after recovery from acute conjunctivitis.
      However, dry eye can be avoided during the treatment of acute conjunctivitis by
      consideration of drug side effects to the tear film and minimizing the
      unnecessary use of drugs.

PMID- 16643734
TI  - [Clinical investigation of chronic blepharitis and evaporative loss dry eye].
AB  - OBJECTIVE: To investigate the relationship between chronic blepharitis and
      evaporative loss dry eye. METHODS: Forty-one patients (82 eyes) were diagnosed as
      chronic blepharitis from November 2002 to April 2003 in Beijing Tongren Eye
      Center, of which 22 cases were male and 19 female. All patients' ocular surface
      was judged by Schirmer I test, tear film break up time (BUT) and Tearscope.
      Meibomian gland secretion was used for bacteria culture and antibiotic
      sensitivity test. Thirty patients (60 eyes) of glaucoma, cataract and LASIK
      before surgery were used as control, which included 16 male and 14 female.
      Microbiological results of meibomian gland secretion were compared and the
      statistical difference was evaluated by chi(2) test. RESULTS: Of the blepharitis
      group, ST value was less than 10 mm in 30 eyes (36.6%), BUT less than 10 s in 56
      eyes (68.3%) and tear film tearscope evaluation more than 3 grade in 46 eyes
      (56.1%). The bacteria spectrum of meibomian secretion in both groups was similar,
      which included staphylococcus epidermidis, staphylococcus aureus and
      corynebacterium. However, the bacterium culture positive rate and antibiotic
      sensitivity showed significant difference (P < 0.05). CONCLUSION: The chronic
      blepharitis is one of important cause in evaporative loss dry eyes.

PMID- 16643735
TI  - [The effect of basic fibroblast growth factor and epidermal growth factor on
      corneal endothelial cells preserved in mid-term preserving medium].
AB  - OBJECTIVE: To investigate the effect of basic fibroblast growth factor (bFGF) and
      epidermal growth factor (EGF) on corneal endothelial cell preserved in mid-term
      preserving medium. METHOD: Corneal rings were preserved in mid-term preserving
      medium in control group. bFGF (5 ng/ml), bFGF (20 ng/ml), EGF and bFGF + EGF were
      added into the mid-term preserving medium in experimental groups A, B, C, D
      respectively. At the 3rd, 7th and 14th day after preservation, the viability of
      corneal endothelial cells (CECs) was assessed by trypan blue and alizarin red
      stain. The microstructure of corneal endothelial cells was observed by electron
      microscope (EM). RESULTS: At the 14th days of preservation, viability of CECs was
      (10.35 +/- 1.32)% (control group), (62.18 +/- 1.56)% (group A), (92.57 +/- 0.90)%
      (group B), (71.01 +/- 2.67)% (group C) and (82.59 +/- 1.45)% in group D
      respectively. The viability of CECs in experimental groups was much higher than
      in control group (P < 0.01). At the 14th days, corneal rings in control group
      showed edematous, cloud, defect of integrity of endothelial cells and Y type
      conjunction broken. But in experimental groups, the corneal edema and folds were
      slightly, furthermore the cornea ring was transparency and cell shape was intact,
      especially in group B and group D. Electronic microscope (EM) showed that corneal
      endothelial cells Y type conjunction in experimental groups was completely
      integrity, endothelial cells had tight conjunction and rich micro-villa on
      surface, large cells body and obvious nucleus. CONCLUSION: Addition of bFGF and
      EGF in corneal storage medium plays a significant role in maintaining CECs
      structure and viability.

PMID- 16643736
TI  - [Statistics analysis of the first authors and their institutions in Chinese
      Journal of Ophthalmology from 2002 to 2004].
AB  - OBJECTIVE: To investigate the first authors and their institutions in Chinese
      Journal of Ophthalmology from 2002 to 2004. METHOD: All of the first authors and
      their institute issued in Chinese Journal of Ophthalmology from 2002 to 2004 were
      collected in the study, the data was statistically analyzed. RESULTS: A total of
      775 articles have been issued on the journal in the period of time. There were
      ten authors who issued more than 5 articles individually at total 79, which
      covers 10.19%. There were 20 institutes in which more then 10 papers were
      published as first author in each institute, covering 60.26% (total 467). As the
      first authors from Non-ophthalmology institute issued 25 articles, covering
      3.23%. CONCLUSIONS: The authors who published the most articles in the journal
      are XIAO Li-hua, XIE Li-xin and ZHAO Jia-liang. The institutes affiliated with
      the first authors that issued the most articles are Eye Research Center of
      Zhongshan University, Eye Research Center of Peking Union Hospital, Capital
      medical university and Shandong Eye institute; Non-ophthalmology institute
      affiliated with the first author are Central Laboratory of the first people's
      hospital, Shanghai Transportation University.

PMID- 16643746
TI  - [Devoting much attention to further understanding the definition of glaucoma].
AB  - This article is intended to briefly introduce the latest new trends and the
      overall current situation surrounding the definition of glaucoma. This article
      also summarizes the difficulties in understanding the definition of glaucoma.
      Included is a theoretical discussion of how to differentiate the traditional and
      modern concepts of glaucoma and how to make glaucoma classification clinically
      practicable and understandable.

PMID- 16643747
TI  - [Three essential elements of glaucomatous optic nerve damage and discrimination
      of optic nerve rim loss].
AB  - Three essential elements of glaucomatous optic nerve damages are optic nerve rim
      loss, retinal nerve fiber layer defects (RNFLD) and optic disc linear
      hemorrhages. It's suggested that if there are two positive signs detected among
      the three elements, the diagnosis of the glaucomatous optic nerve damages can be
      established. There is no definitely described how to identify optic nerve rim
      loss in the previous textbooks, therefore it is important to know about the
      morphological features of the physical optic nerve rim and influence factors
      before discrimination of optic nerve rim loss. Most of physical optic nerve rim
      are in accordance with ISNT rule, physical large optic cups are also accord with
      ISNT rule. Exceptional cases exist in two patterns, optic nerve rim loss or
      normal optic nerve rim morphological variances. The latter includes part of small
      discs, horizontally oval optic discs, the position of the central retinal vessel
      trunk and the titled optic discs which affect the morphological feature of optic
      nerve rim as well. In some small discs, the width of inferior rim is narrower
      than that of superior rim, therefore, the inferior or the superior rim loss can
      be evaluated by comparison with nasal rim width. Concerning horizontal oval optic
      discs, the width of inferior rim and superior rim should be compared to evaluate
      whether there is the optic nerve rim loss. If those patterns of normal optic
      nerve rim variances can be recognized, it is not difficult to find the presence
      of the optic nerve rim loss. However, not all of the optic nerve rim loss is due
      to glaucomatous optic nerve damages, non-glaucomatous optic nerve damage should
      be distinguished.

PMID- 16643748
TI  - [The measurement of central corneal thickness of normal subjects and glaucomatous
      patients with optical coherence tomography].
AB  - OBJECTIVE: To evaluate central corneal thickness (CCT) of normal subjects,
      patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG)
      and ocular hypertension (OHT) using optical coherence tomography (OCT). METHODS:
      One hundred and forty-three eyes of 143 normal subjects, 36 eyes of 36 patients
      with POAG, 39 eyes of 39 patients with NTG and 40 eyes of 40 patients with OHT
      were enrolled. CCT were measured by OCT3 and analyzed using ANOVA. The
      relationship of CCT and intraocular pressure (IOP) measured by Goldmann
      applanation tonometry were analyzed by linear regression. The inter-observer and
      intra-observer agreement of CCT measurement by OCT were analyzed by interclass
      correlation coefficient (ICC). RESULTS: The average CCT of normal subjects,
      patients with POAG, NTG and OHT were (525.31 +/- 32.18) microm, (531.87 +/-
      31.58) microm, (507.61 +/- 21.56) microm and (574.09 +/- 27.84) microm,
      respectively. There was no significant difference between normal subjects and
      patients with POAG (P = 0.099). The average CCT of OHT patients was larger than
      those of other groups (P < 0.001). The average CCT of patients with NTG was less
      than those of other groups (P < 0.001). There was positive relationship between
      CCT and IOP in normal subjects (r = 0.318, R2 = 0.101, P < 0.001). The ICC of
      inter-observer and intra-observer agreement of CCT measurement by OCT were 0.995
      and 0.996 respectively. CONCLUSIONS: Central corneal thickness could be measured
      by OCT accurately. The average CCT in the patients with NTG was thinner, but the
      average CCT in the patients with OHT was thicker than that of normal subjects.
      CCT could affect IOP measurement in the application of Goldmann applanation
      tonometry but with little significant.

PMID- 16643749
TI  - [The interrelationship between the sectorial disc and the visual field changes in
      patients with normal tension glaucoma].
AB  - OBJECTIVE: To investigate the changes of the sectorial discs and visual fields,
      and their interrelationships in patients with normal tension glaucoma (NTG).
      METHODS: 26 patients with NTG were undergone the optic nerve and visual field
      examinations with HRT-II and HFA II in a time interval of less than 5 months. The
      parameters in the study including cup shape measure (CSM), rim area (RA), rim
      volume (RV), mean cup depth (MCD) and cup volume index (CVI) were compared
      between the global discs and the sectorial discs in eyes with the evidences of
      preperimetric or early visual field defect (MD < or = 4 dB). The CVI was proposed
      to be equal to CV/(DA x MCD + RA x RNFLT), where DA was disc area and RNFLT was
      retinal nerve fiber layer thickness. The linear correlations were evaluated
      between the visual field MD and each of 5 parameters in sectorial discs. RESULTS:
      The sectorial disc areas were mostly in correspondence to the damaged hemifields
      (CVI: 92.68%, RA: 87.80%, RV: 82.93%). In addition, a correlation was seen for
      CSM and MCD (63.41% and 53.66%; chi2 = 23.17, P < 0.05). The comparison between
      preperimetric and early defects were significantly difference (t = 1.735
      approximately 6.536, P < 0.05 approximately P < 0.05, one-sided t test). The
      correlation between CSM and MD was negative (r = -0.3002, P > 0.05), however the
      positive correlation was demonstrated in RA versus MD (r = 0.3105, P < 0.05).
      CONCLUSION: The examination of the 5 parameters of sectorial discs had even
      closer relationship than those of global discs scanning in the detection of early
      vision field defect and it is valuable in diagnosis of early glaucoma.

PMID- 16643750
TI  - [The action of dexamethasone on trans epithelial electrical resistance and the
      expression of aquaporin-1 in immortalized trabecular cells].
AB  - OBJECTIVE: To study the effect of dexamethasone on trans epithelial electrical
      resistance (TEER) and the expression of AQP-1 in immortalized trabecular cells.
      METHODS: Immortalized human trabecular cells were cultured on PET membrane in 24
      wells plate. The cells were treated with Dexamethasone in concentration of 10(-7)
      mol/L. After the cultured cell became confluence, TEER of the cells was detected
      to evaluate the resistance of outflow pathway at different time points. Western
      blot was used to analyze the expression of AQP-1 in the trabecular cells.
      RESULTS: The TEER and the expression of AQP-1 were much higher in the cells
      treated by Dexamethasone in comparison to control without dexamethasone exposure.
      CONCLUSIONS: The TEER and expression of AQP-1 in immortalized trabecular cells
      can be enhanced by Dexamethasone. AQP-1 upregulation induced by Glucocorticoid
      may relate with the increased resistance of outflow pathway in glaucoma.

PMID- 16643751
TI  - [Anti-proliferative effect of herpes simplex virus thymidine kinase gene system
      on human Tenon capsule fibroblasts in vitro].
AB  - OBJECTIVE: To observe anti-proliferative effect of herpes simplex virus thymidine
      kinase gene system (HSV-tk) on human Tenon capsule fibroblasts (HTFs) and it's
      mechanism. METHODS: Retroviral vector was constructed containing HSV-tk gene and
      transfer to packaging cell line PT67. The positive clones was selected with G418
      and the supernatant was collected which contains virus particles. The titer of
      the virus was also calculated. The virus particles were verified by transmission
      electron microscope (TEM). PCR was carried out to detect the integrity of tk gene
      into viral DNA genome. HTFs cells were infected with the virus and the positive
      clones were selected for propagation culture. RT-PCR and Western blot were used
      to detect tk gene expression. The anti-proliferative effect of tk gene on HTFs
      cells was determined by MTT. Apoptosis of cells was detected by Hoechst 33258 DNA
      staining and flow cytometry. The morphologic changes of the cell were observed by
      TEM. RESULTS: The retroviral vector pL (tk) SN was constructed successfully which
      was verified by enzyme cutting. The shape of virus particles derived from the
      package cells appeared to be oval or spherical under TEM with the diameter around
      100 nm. The tk gene was detected in the viral DNA genome by PCR. The virus titer
      was 4 x 10(7) cfu/ml. The expression of tk gene was detected by RT-PCR and
      Western blot both in mRNA and protein level. The anti-proliferative effect of tk
      gene on HTFs cells was dose-dependent, all cells were died 5 days after 5 x 10(
      3) g/L GCV being added, IC50 = 6 x 10(-4) g/L. Both necrosis and apoptosis were
      observed in this study and the apoptosis rate was increased with increasing dose
      of GCV. CONCLUSIONS: The proliferation of HTFs cells in vitro could be
      effectively inhibited by the killing effect of HSV-tk-GCV system through the
      pathway of necrosis and apoptosis.

PMID- 16643752
TI  - [Radiation therapy for thyroid-associated ophthalmopathy].
AB  - OBJECTIVE: To observe indication and effectiveness of radiation therapy (RT) in
      the treatment of the patients with thyroid-associated ophthalmopathy (TAO).
      METHODS: 23 patients of TAO who received RT in Sichuan University were collected
      from 1992 to 2004. Among those patients, 9 cases of infiltrative exophthalmos and
      14 cases of compressive optic neuropathy were ineffectively with glucocorticoid
      treatment or could not treated with glucocorticoid, or could not perform orbital
      decompression due to severe diabetic mellitus or hypertension, or feared to
      receive the operation, all of patients were active ophthalmopathy and with short
      duration. Outer orbital radiation was applied using linear accelerator with
      Donaldson's method, radiation treatment fields was 4 cm x 5 cm, exposure energy
      was 2 GY fractions with total of 20 GY. In 11 cases with severe inflammation
      prednisone was administered during radiotherapy. Photos and CT scan were taken
      for each patient before and after RT. RESULTS: Visual acuity (VA) of the patients
      was improved from before RT 0.04 - 0.2 to after RT 0.1 - 0.8 in 14 cases of
      compressive optic neuropathy. Extraocular muscle of patients decreased in size
      confirmed by CT scan. VA improvement was correlated with the degree of
      extraocular muscle decreased in size. Eyelid and conjunctive swelling, eyelid
      incompletely closure, exposure keratitis, limitation of motion and proptosis were
      improved after RT in 9 patients with infiltrative exophthalmos. Following up the
      patients for 1 - 3 years, it was found that VA decreased in 3 cases and
      inflammation recurred in 4 cases, eyelids could not closed in 2 cases after RT.
      CONCLUSIONS: RT could be used in severe, active cases of TAO. If there is severe
      inflammation, steroids could be combined with RT therapy.

PMID- 16643753
TI  - [Study on the growth of orbital volume in individuals at different ages by
      computed tomography].
AB  - OBJECTIVE: To study the growth aspects of orbital volume and to establish the
      normal value of orbital volume by computed tomography (CT). METHODS: One hundred
      and twenty three individuals without eye diseases (64 males, 59 females) were
      divided into 5 groups according to the age. Orbital volume and length of
      horizontal transverse axis and anterior-posterior axis of the eye were measured
      at different levels in original or reconstructive CT images. The relationship
      between orbital volume and age, gender and eyeball volume was analyzed. RESULTS:
      There was no difference between the left and right orbital volume in all age
      groups. Orbital volume grew rapidly before 20 years of old. Mean orbital volume
      in males aged 17 and females aged 13 was 23.54 and 21.75 ml, respectively, which
      reached 95% of the adult orbital volume. In normal adult, orbital volume in the
      male was larger than that of the female. The mean orbital volume of adult male
      and female was (25.04 +/- 2.37) ml and (22.89 +/- 2.67) ml, respectively. A
      strong linear correlation was presented between the age and orbital volume (P <
      0.05). The difference of orbital volume between the male and female was
      statistically non-significant before 14 years old (P = 0.315). The growth of
      eyeball volume was consistent with that of the orbital volume, the ratio of
      eyeball/orbit volume was decreased with age from 0.40 to 0.26. CONCLUSIONS: There
      is no difference between the right and left orbital volume. Orbital volume is
      correlated with age and gender. Orbital volume grows rapidly before 20 years of
      old and still grows slowly after 40 years old.

PMID- 16643754
TI  - [Visual field analysis after laser in situ keratomileusis].
AB  - OBJECTIVE: To evaluate the effects of laser in situ keratomileusis (LASIK) on the
      patients' visual field. METHODS: 92 eyes of 46 patients with mild, moderate, and
      high degrees of myopia were undergone LASIK. Perimetry was performed before and 1
      day, 1 month, 3 months, 6 months after LASIK surgery by Humphrey II-750 visual
      field analysis. The central 30 - 2 fast threshold program was used to examine the
      change in central 30 degree. Mean defect (MD) and pattern standard deviation
      (PSD) were record. All operations were performed by an experienced surgeon.
      Statistical analyses were performed by SPSS using the randomized complete block
      design ANOVA (two factors analysis of variance). Differences among variables were
      evaluated by q-test (Student-Newman-Kueuls method). RESULTS: 93.5% patients
      obtained estimated best correct visual acuity or better at six months after
      LASIK. No complications were found in the subjects. No difference was found in
      fundus examinations before and after surgery. Intraocular pressure was normal at
      all preoperative and postoperative examinations. MD was significant differences
      among preoperative and postoperative values (P < 0.05, for all comparisons) and
      was correlated with visual acuity post-LASIK significantly (P < 0.05). While PSD
      did not show significant differences before and after LASIK (P > 0.05) and was
      not correlated with visual acuity post-LASIK. The indexes of visual field were
      not correlated with the degree of myopia and the other surgical parameters (P >
      0.05). CONCLUSION: In current research, no significant visual field change was
      demonstrated pre-LASIK and post-LASIK after 6 months follow-up. The study
      suggests that LASIK does not affect the retinal physiological functions.

PMID- 16643755
TI  - [The analysis of corneal topography for keratoconus].
AB  - OBJECTIVE: To investigate the refraction and videokeratographic characteristics
      of keratoconus. METHODS: 262 eyes of 147 patients with keratoconus were examined
      using autorefractor and computerized corneal topography, which generated the
      quantitative descriptors including refraction, keratometry, corneal astigmatism,
      the surface regularity index (SRI), the surface asymmetry index (SAI), and
      morphologic description. RESULTS: All patients were classified into four groups:
      suspect, mild, moderate and advanced group. The topographical configurations of
      the lesions were divided into bow-tie pattern subdivided into symmetric and
      asymmetric pattern, and non-bow-tie pattern including nipple, oval, global and
      anomalistic pattern. The bow-tie pattern mostly appeared symmetrical and occurred
      in suspect and mild cases. The nipple and oval pattern mostly occurred in mild
      and moderate ones located in the central or inferior paracentral cornea. The
      global pattern mostly occurred in moderate and advanced ones located in the
      central cornea. The anomalistic pattern occurred in advanced ones. Bilateral
      topography showed symmetrical in majority of patients with bilateral keratoconus.
      There was no correlation between the diameter of lesion and the refraction power
      of corneal apex (r = 0.208, P = 0.092). There was negative correlation between
      the distance from corneal center to the apex of lesion and the refraction power
      of corneal apex (r = -0.400, P = 0.001). CONCLUSIONS: Corneal topography is a
      sensitive method to detect the keratoconus earlier, which helps eye doctors to
      take appropriate measures to improve patients vision and avoid patients from
      undergoing excimer laser keratorefractive surgery. In addition, it can show the
      configuration of the lesion, which guide the fitting of hard contact lens.

PMID- 16643756
TI  - [Early clinical evaluation of visual function in patients with age-related
      cataract].
AB  - OBJECTIVE: To investigate the characteristics of visual acuity, contrast
      sensitivity and glare contrast sensitivity in age-related cataract patients.
      METHODS: In this study, 115 eyes of 66 age-related cataract patients with a best
      corrected visual acuity of 0.5 or better, who had been classified into cortical
      cataract group (50 eyes of 31 subjects), nuclear sclerosis group (32 eyes of 17
      subjects), posterior subcapsular cataract group (33 eyes of 18 subjects); and
      control group (34 eyes of 34 subjects) were examined with a contrast glare tester
      to assess contrast sensitivity and glare contrast sensitivity. RESULTS: There
      were statistically significant differences among contrast sensitivity and glare
      contrast sensitivity in the cataract patients with different visual acuity at
      low, medium spatial frequency (P < 0.01); there were no statistically significant
      differences among those at high spatial frequency (P > 0.05). Cortical cataract
      was associated with the contrast sensitivity at low, medium spatial frequency,
      where the glare contrast sensitivity fell into at low, medium and high spatial
      frequency; in the patients with cataract of nuclear sclerosis was associated with
      the contrast sensitivity at low spatial frequency, where the glare contrast
      sensitivity was at low, medium and high spatial frequency; in contrast to
      posterior subcapsular cataract both the contrast sensitivity and glare contrast
      sensitivity (at low, medium, high spatial frequency) were lower than normal eyes
      (P < 0.05). Each spatial frequency of contrast sensitivity and glare contrast
      sensitivity in 57 cataract eyes with a best corrected visual acuity of 0.8 or
      better were lower than normal eyes. In those eyes the contrast sensitivity at low
      spatial frequency and glare contrast sensitivity at low and high spatial
      frequency had statistically significant difference compared with control (P <
      0.05); other spatial frequency had no statistically significant difference among
      groups (P > 0.05). The glare contrast sensitivity in cataract eyes was lower than
      contrast sensitivity at visual angle of 6.3 degrees, 4.0 degrees, 2.5 degrees,
      1.6 degrees, 1.0 degrees, the difference was statistically significant (P <
      0.01). CONCLUSION: Contrast sensitivity and glare contrast sensitivity are
      reliable in evaluating visual function in the patients with early age-related
      cataract.

PMID- 16643757
TI  - [Expression of heat shock protein 70 and heat shock protein 27 in lens epithelial
      cells induced by contusion and thermotolerance in rat model].
AB  - OBJECTIVE: To study the dynamic expression of heat shock protein (HSP) 70 and
      HSP27 in lens epithelial cells (LECs) in contused eyes of rat model and to detect
      the dynamic change of the expression of HSP70 and HSP27 after thermotolerance.
      METHODS: Forty-eight Sprague-Dawley (SD) rats were randomized into two groups:
      contusion group and thermotolerance group. Contusion eyes were induced by
      dropping a steel ball of 20 g from the height of 20 cm for 100 times.
      Thermotolerance was induced by raising the core body temperature of rat to 40.5
      41.5 degrees C for 8 min, 2-3 h before eyes contusion. HSP70 and HSP27 expression
      in the LEC were measured using one-tube RT-PCR. RESULTS: Contusion of eyes
      resulted in increase of HSP70 expression. Expression of HSP70 increased to 4.59
      +/- 0.12 at 1 h after contusion, reached the highest level of 7.72 +/- 0.27 at 3
      h after contusion, and reduced to the normal level of 1.32 +/- 0.14 at 24 h after
      contusion. Preconditioning hyperthermia resulted in significantly increase of
      HSP70 expression. There was no significant change of HSP27 expression in both
      groups. CONCLUSIONS: Increased expression of HSP70 in LECs of contused eyes
      possibly protects the proteins of lens against degeneration. Thermal
      preconditioning might suppress lens injury induced by contusion via increasing
      the expression of HSP70.

PMID- 16643758
TI  - [Experimental study on repairing damage of corneal surface by mesenchymal stem
      cells transplantation].
AB  - OBJECTIVE: To investigate the survival, migration and differentiation of the
      cultured human mesenchymal stem cells derived from bone marrow (hMSCs) after
      transplanted onto the alkaline burn rabbit cornea. METHODS: Alkaline burn on
      rabbit corneas was induced with NaOH solution. One month later, hMSCs cultured
      with a feeding of amniotic membrane were transplanted onto the surface of
      alkaline burn rabbit corneas. Amniotic membrane alone transplantation was used at
      the same time as control group. One month after transplantation, the changes of
      corneal morphology were analyzed by clinical observations and HE staining.
      Immunohistochemistry was carried out with the antibodies against human nuclei and
      cytokeratin 12 to investigate the distribution and differentiation of hMSCs.
      RESULTS: The rabbit cornea became totally opaque one month after alkaline burn.
      Blood vessels could be seen within the superficial layer and stroma. The surface
      of cornea was rough and dry. There were many goblet cells found in the corneal
      epithelial layer. One month after transplantation of hMSCs, the surface of
      alkaline burn cornea became smoother. The amount of the new blood vessels of the
      cornea reduced and the goblet cells disappeared. Anti-human nuclei antibody
      staining showed positive cells on the surface layer and superficial stroma while
      cytokeratin 12 positive cells were only present in the epithelium layer. In the
      amniotic membrane transplantation control group, no clinical improvement of the
      cornea was found. Goblet cells were still seen on the corneal surface. Both anti
      human nuclei antibody and cytokeratin 12 staining were negative. CONCLUSIONS:
      hMSCs survive and migrate to stroma after transplanted onto the surface of
      alkaline burn rabbit cornea. No rejection is detected. hMSCs on the corneal
      surface differentiate to corneal epithelium, where those migrated to the stroma
      differentiate to cells other than epithelium. hMSCs transplantation decrease
      corneal conjunctivization after alkaline burn.

PMID- 16643759
TI  - [Regeneration of optic nerve fibers following graded injuries in rats].
AB  - OBJECTIVE: To investigate the changes of retinal ganglion cell (RGC) and their
      axons, and nerve regeneration ability following graded optic nerve injury (ONI)
      in rats. METHODS: A pair of cross-action forceps with 148.0 g clipping pressure
      was used to clip rat optic nerves for 3, 6, 12, 30 and 60 s to induce graded ONI
      animal model. The RGC was counted at 0.5, 1, 2, 3 and 7 months and the axons were
      observed 1, 2 and 3 months post-injury. The regeneration process was observed by
      transmission electron microscopy. The number of optic nerve fibers in transverse
      sections was calculated in silver-stained longitudinal sections, and a
      regeneration index (RI) was calculated based on these numbers. The RI, reflecting
      the regeneration ability of injured optic nerves, was calculated as follows:
      (number of nerve fibers 0.5 mm behind injury site-number of nerve fibers 2.5 mm
      behind injury site)/(number of nerve fibers 0.5 mm retrobulbarly-number of nerve
      fibers 2.5 mm behind injury site). RESULTS: RGC and axons lost continuously after
      partial ONI. The loss of RGC was fitted with exponential pattern consisted of two
      phases, acute losing phase within first two weeks post injury and followed by
      another phase characterized by slowly reducing of RGC. The loss ratio of RGC
      increased and the survival ratio decreased with the severity of injury intensity.
      The loss of RGC and axons was aggregated in severe injury and showed a self
      limited trend in mild injury. A large amount of clustered, zonal unmyelinated
      regeneration fibers were present after injury. The RI was 1.409, 1.490, 0.916,
      1.119 and 1.224 following 3, 6, 12, 30 and 60 s clipping injury (chi2 = 281.2, P
      < 0.01), respectively. Different RI was associated to different injury intensity,
      with a greater regeneration ability in mild injury. CONCLUSIONS: The secondary
      reaction and regeneration ability vary with graded intensity of optic nerve
      injury. A self-limited secondary reaction and a more powerful regeneration
      ability are associated with a mild injury. The repair behavior and the injury may
      reach a balance and result in a successful regeneration after a certain degree of
      injury.

PMID- 16643760
TI  - [Effects of experimentally induced hyperopic optical defocus on refractive status
      of adolescent monkeys].
AB  - OBJECTIVE: To determine if chronic optical defocus alters refractive development
      in monkeys at ages corresponding to the typically developed age of myopia in
      human children. METHODS: A hyperopic anisometropia was produced in 7 adolescent
      rhesus monkeys by photorefractive keratectomy (PRK). The laser procedures were
      performed when the monkeys were 2.0 to 2.5 years old, which corresponded to
      approximately 8-10 years old in human being. The ocular effects of the induced
      anisometropia were assessed periodically by corneal topography, retinoscopy and A
      scan ultrasonography. RESULTS: By about 30 days post-PRK, the experimentally
      induced refractive errors was stabilized and the treated eyes were between +0.75
      and +2.25 D more hyperopic than their fellow eyes. Subsequently, 7 monkeys showed
      systematic reductions in the degree of anisometropia. Although some regression in
      corneal power occurred, the compensating refractive changes were primarily due to
      the differences in vitreous chamber growth (r = 0.74, P = 0.046). CONCLUSIONS:
      Vision-dependent mechanisms that are sensitive to refractive error are still
      active in adolescent primates and probably play a role in maintaining stable
      refractive errors in the two eyes. Consequently, conditions that result in
      consistent hyperopic defocus could potentially contribute to the development of
      juvenile onset myopia in children.

PMID- 16643762
TI  - [Design of a quantitative keratoscope used for ocular microsurgery].
AB  - A new quantitative keratoscope used specially for ocular microsurgery to measure
      corneal astigmatism is reported. A combined cylinder-lens, which power can be
      changed by rotating lens in anti-direction equally, was designed according to the
      principal of the crossing cylinder lens. The axis direction is fixed when the
      lens is rotated. The corneal astigmatism can be measured by changing the power of
      the combined lens to adjust the corneal ring images. The keratoscope could be
      used to measure the corneal astigmatism quantitatively specially for ocular
      microsurgery. At the work-distance of 0.025 m, the maximum power of measured
      astigmatism was up to 8.50 D. The error of the measurement was less than 0.20 D.
      The keratoscope is a portable lens to be used easily during the ocular
      microsurgery. The reporting keratoscope is a simple combined cylinder-lens that
      can be used to measure corneal astigmatism, including the power and the axis of
      astigmatism, easily during ocular microsurgery.

PMID- 16643767
TI  - [Aging and age-related macular degeneration].
AB  - Aging is a common feature of biological changes in the eye, especially in the
      retina. It is recognized that the pathogenesis of age-related macular
      degeneration (AMD) involves changes of RPE-Bruch membrane and choroid capillaries
      complex, which includes function and structure abnormal in the complex
      accompanied with aging processes. Aging may be an important event to contribute
      to the pathogenesis of AMD, but aging dose not directly led to the occurrence of
      AMD, multifactor is involved in the initiation of the pathogenesis of AMD.
      Therefore, this review is summarizing the latest concepts of the rale of aging in
      the occurrence of AMD.

PMID- 16643769
TI  - The diagnosis and management of oral herpes simplex infection.
AB  - Acute herpetic gingivostomatitis and recurrent herpes labialis are the most
      common manifestations of infection with herpes simplex virus type 1 (HSV-1). In
      primary and recrudescent HSV-associated disease, the symptoms may range from
      subclinical to debilitating and life-threatening, depending on the host's immune
      responses or competence level. In this paper, the typical and atypical
      manifestations, and the current diagnostic and treatment options for localized,
      non-complicated oro-labial HSV infection are reviewed, with attention to
      cumulative evidence for the efficacy and safety of systemic antiviral agents.
      Some recent data on HSV-1 seroprevalence, viremia, and viral shedding are
      discussed in relation to disease transmission and global importance of
      herpesvirus disease.

PMID- 16643770
TI  - The use of tympanocentesis in the diagnosis and management of acute otitis media.
AB  - Acute otitis media (AOM), when associated with a bulging or full tympanic
      membrane, has a bacterial etiology in more than 90% of cases. Not infrequently,
      the organisms present express resistance mechanisms to commonly prescribed
      antibiotic therapy. Tympanocentesis is a procedure advocated by several national
      guidelines for use in selected patients not clinically responding to
      antimicrobial treatment. In this paper we discuss the use of tympanocentesis as a
      tool to track pathogen shifts and to guide antibiotic selection. We detail the
      indications for tympanocentesis, compare guidelines endorsing the procedure, and
      describe how to implement a technique for use in the primary care setting. The
      pros and cons of using tympanocentesis in clinical trial designs are also
      presented.

PMID- 16643771
TI  - Medical and surgical treatment of peritonsillar, retropharyngeal, and
      parapharyngeal abscesses.
AB  - Peritonsillar, retropharyngeal, and parapharyngeal abscesses are the most common
      deep cervical fascial space infections. Most develop secondary to an
      oropharyngeal or dental infection. Additional factors such as smoking and
      periodontal disease may also contribute to the formation of a peritonsillar
      abscess. The CT scan is used to confirm the presence of deep neck abscesses, but
      its accuracy has some limitations. Adequate drainage with accompanying
      antimicrobial therapy and hydration are the cornerstones of management. Catheter
      or needle drainage of these abscesses may provide an alternative to open
      procedures and is the drainage method of choice for peritonsillar abscesses.
      However, in selected cases, medical therapy alone, especially in children, can
      resolve parapharyngeal and hypopharyngeal abscesses. Ancillary use of steroids
      reduces morbidity in patients with a peritonsillar abscess and there is a limited
      but useful place for immediate tonsillectomy in the treatment of this disease.

PMID- 16643772
TI  - The role of interventional pulmonary procedures in the management of post
      obstructive pneumonia.
AB  - Post-obstructive pneumonia is the result of airway obstruction, commonly due to
      lung cancer. The majority of patients with lung cancer are non-operable and
      incurable at initial presentation. The clinical course of these patients is
      steadily downhill with complicating events such as post-obstructive pneumonia,
      respiratory failure, pleural effusion, and severe debilitation. Non-invasive
      conventional options for post-obstructive pneumonia include broad-spectrum
      antibiotics, combined with attempts at relieving the obstruction using radiation
      therapy. There is scant literature on the natural course of post-obstructive
      pneumonia, disease resolution, and optimal treatment. With the recent surge in
      technologic advances in interventional pulmonology, multiple airway recanalizaton
      options are now available. In this paper, we describe the causes of post
      obstructive pneumonia, and the role of interventional pulmonary procedures in 
      establishing an open airway.

PMID- 16643773
TI  - The other siblings: respiratory infections caused by Moraxella catarrhalis and
      Haemophilus influenzae.
AB  - Respiratory infections remain substantial causes of morbidity and mortality
      globally. In this paper, two substantial players in bacterial-associated
      respiratory disease are assessed as to their respective roles in children and
      adults and in the developed and developing world. Moraxella catarrhalis, although
      initially thought to be a nonpathogen, continues to emerge as a cause of upper
      respiratory disease in children and pneumonia in adults. No vaccine is currently
      available to prevent M. catarrhalis infection. Haemophilus influenzae type b,
      originally thought to be the cause of influenza, has now been limited
      epidemiologically in the developed world due to an effective immunization but it
      continues to be a major player in the developing world. Nonencapsulated strains
      of H. influenzae still remain as significant causes of respiratory infections in
      the developing world especially in exacerbation of chronic obstructive lung
      disease. Finally, and in brief, the spectrum of Brazilian purpuric fever due to a
      specific biotype of H. influenzae is discussed.

PMID- 16643774
TI  - Pneumonitis in human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) is a beta herpes virus with a double stranded DNA
      genome of 240kbp. The virus is prevalent and establishes a latent infection in
      most adults. HCMV is an opportunistic pathogen for patients with impaired
      cellular immunity. HCMV pneumonia is a common presentation of HCMV disease in
      immunocompromised patients. The incidence of HCMV pneumonitis can be as high as
      90% in lung transplant recipients. This paper takes a fresh look at the
      challenging perspectives of molecular, immunologic, cellular, diagnostic,
      clinical, and therapeutic characteristics of HCMV infection as future targets for
      development of antiviral strategies.

PMID- 16643775
TI  - Strategies for improving pneumococcal vaccination in eligible patients.
AB  - Despite the fact that invasive Streptococcus pneumoniae remains a leading cause
      of death, current levels of immunization in the at risk population remain low and
      well below the 90% goal for Healthy People 2010. A number of intervention
      strategies to increase immunization rates (for influenza and pneumonia) have been
      demonstrated to be effective in increasing these rates when used alone or in
      combination. A summary of this literature is presented including recent data on
      the effectiveness of pay-for-performance approaches for increasing preventive
      care. Data are also presented on intervention strategies judged to be most
      effective in a large health care system, the Veterans Health Administration,
      which has essentially reached the Healthy People 2010 goal for pneumococcal
      immunization.

PMID- 16643776
TI  - HIV and aging.
AB  - Approximately one in five individuals living with HIV infection in the United
      States is 50 years of age or older. This proportion continues to increase as HIV
      incidence remains stable and potent antiretroviral therapy has reduced the
      morbidity and mortality associated with HIV infection. Newly identified HIV
      seropositive older individuals are proportionately more likely than younger
      persons to have AIDS at the time of diagnosis. Clinicians have to think about the
      possibility of HIV infection in older persons to avoid delays in diagnosis and
      treatment. Immunologic recovery in older individuals initiated on combination
      antiretroviral therapy is less robust in some studies compared with younger
      individuals. However, virologic suppression on treatment in young versus old
      antiretroviral naive patients is comparable. Co-morbid conditions and their
      treatment pose a special challenge to health care providers with regard to drug
      metabolism and interactions with HIV medications. HIV prevention should be
      discussed with all at risk individuals. The HIV epidemic will only worsen if
      medical practitioners neglect to discuss sexual risk behavior with their older
      patients.

PMID- 16643777
TI  - [Expression and immunogenicity analysis of a recombinant fusion protein of V.
      Cholera ctB and H. pylori ure I].
AB  - AIM: To express fusion protein of the cholera toxin B subunit (ctB) and the urea
      membrane channel gene (ure I) of H. pylori in E. coli, and analyze its
      immunogenicity. METHODS: The prokaryotic expression vector pET32a+/ctB/ure I was
      constructed by inserting ctB gene amplified by PCR into the 5' terminus of ure I
      gene of expression vector pET32a+/ure I. The fusion gene was verified by
      endonuclease digestion and sequence analysis. The fusion protein ctB/ure I was
      expressed in E. coli BL21(DE3), purified by His-HP affinity chromatography, and
      analyzed by SDS-PAGE, Western blot and Pro-gel analyzer 4.0. The mice were
      immunized with purified ctB/ure I, and the immunoreactivity with ctB and ure I of
      the murine sera was analyzed by indirect ELISA. RESULTS: The pET32a+/ctB/ure I
      expression vector was constructed successfully and confirmed by endonuclease
      digestion and sequence analysis. The expressed ctB/ure I protein with molecular
      weight about 58,000 was shown when induced with 1 mmol/L IPTG for 4 h at 22
      degrees C, and the protein could react with horse anti-ctB and human anti-ure I
      sera when detected with Western blot, and the purity of the purified protein was
      about 94.3%. The sera from mice immunized with purified ctB/ure I protein could
      react with ctB, ure I, and ctB/ure I when detected with indirect ELISA.
      CONCLUSION: The fusion protein expression vector pET32a+/ctB/ure I was
      constructed successfully. The fusion protein ctB/ure I was shown to have
      immunoreactivity with both anti-ctB and anti-ure I anti-sera, and could evoke
      production of anti-ctB and anti-ure I antibody in mice. Our work established a
      good foundation for further study on the new and effective H. pylori vaccines.

PMID- 16643778
TI  - [Construction of Tet-on inducible CXCR1 eukaryotic expression plasmid and
      identification of the expression character in NIH3T3 cells].
AB  - AIM: To construct tetracycline (Tet)-controlled inducible vector CXCR1-pTREhyg,
      and then detect the expression character of CXCR1 under the regulation of Dox in
      NIH3T3 cells. METHODS: A full length cDNA of human CXCR1 was cloned from sample
      of fibroblast like synovium (FLS) in rheumatoid arthritis (RA) patient by RT-PCR
      and then sub-cloned into the pTREhyg plasmid after sequence analysis. CXCR1
      pTREhyg and pTet-on was co-transfected with Lipofect2000 to NIH3T3 cells, and the
      expression of IL-8RA was detected by Western blot after given different
      concentration of Dox. RESULTS: Western blot showed that CXCR1 could be induced by
      Dox in NIH3T3 cells, and the phosphorylated Erk-1/2 level was significantly
      increased after IL-8 stimulation. CONCLUSION: Tet inducible recombinant vector of
      CXCR1-pTREhyg was successfully constructed, and it could be expressed in NIH3T3
      cells. The stimulation of IL-8 obviously changed the activity of Erk-1/2 in the
      transfected NIH3T3 cells. This work has laid foundations for further study on the
      relationship between CXCR1 and RA disease.

PMID- 16643779
TI  - [Expression of Crg-2 by a bacteria recombinant system of adenovirus].
AB  - AIM: To express an immunochemotactic and angiostatic anti-tumor molecule, CXC
      chemokine Crg-2, by E. coli recombinant system of adenovirus. METHODS: By E. coli
      recombination system of adenovirus, the shuttle vector pShuttle-cmv/crg-2 was co
      transfected into BJ5183 E. coli with adenovirus backbone plasmid pAdEasy-1. The
      recombinants were transfected into 293 packaging cells and adenovirus was
      packaged and amplified. The molecular weight and bioactivity of recombinant
      protein were determined by Western blot and chemotaxis assay, respectively.
      RESULTS: Recombinant adenovirus genome backbone bearing crg-2 gene, pAd/crg-2,
      was successfully obtained as evidenced by endonucleases digestion and PCR.
      Adenovirus was packaged and amplified to a titre of 4x10(9) TCID50/L. The
      cultured supernatant of the infected 293 cells contented a protein of nearly
      10,000 and presented a significantly chemotatic effect towards activated spleen
      lymphoblasts. CONCLUSION: Recombinant adenovirus Ad/crg-2 obtained by E. coli
      recombinant system of adenovirus can efficiently express bioactive Crg-2
      chemokine.

PMID- 16643780
TI  - [Construction of recombinant eukaryotic expression plasmid of murine chemokine
      MIP-1alpha and coimmunization with HSV-II DNA vaccine].
AB  - AIM: To construct the recombinant eukaryotic expression plasmid of murine
      macrophage inflammatory protein-1alpha (MIP-1alpha) and investigate the effect of
      MIP-1alpha as an adjuvant on immune response induced by herpes simplex virus type
      II glycoprotein D (HSV-II gD) DNA vaccine. METHODS: Using total RNA from RAW264.7
      cells stimulated with LPS, the whole code sequence of murine MIP-1alpha was
      amplified by RT-PCR and inserted into pcDNA3 at Hind III/Xba I restriction sites.
      The recombinant eukaryotic expression plasmid Pm was transiently expressed in COS
      7 cells and its specificity was demonstrated by RT-PCR and Boyden chemotaxis
      chamber assay. BALB/c mice were immunized with gD DNA vaccine and/or MIP-1alpha,
      and the effect of MIP-1alpha on gD DNA vaccine was evaluated by detecting anti
      HSV-II antibody, antigen-specific lymphoproliferative responses, and examining
      survival rates after mice were challenged intravaginally with HSV-II. RESULTS:
      The recombinant eukaryotic expression plasmid of murine MIP-1alpha was
      constructed, and it was revealed that immune responses of HSV-II gD DNA vaccine
      were enhanced by coimmunization with MIP-1alpha. CONCLUSION: The murine MIP
      1alpha can be used as an adjuvant of HSV-II gD DNA vaccine.

PMID- 16643781
TI  - [Construction of eukaryotic expression vector of siRNA specific for MAD2 and its
      effect on the growth of gastric cell line SGC7901].
AB  - AIM: To construct the RNA interference eukaryotic expression vector specific for
      human MAD2 gene and to observe its effect on the growth of gastric cancer cell
      line SGC7901. METHODS: The expression vectors of pSilencer3.1/MAD2-siRNA1 and
      pSilencer3.1/MAD2-siRNA2 were constructed by gene recombination and then were
      stably transfected into the gastric carcinoma cell line SGC7901 by liposome
      mediation. The expression of MAD2 on the levels of protein and mRNA was detected
      by Western blot and RT-PCR, and the monoclone with the highest inhibition
      efficiency was selected. The growth of the transfected cells was assessed by MTT.
      And the cells treated with 1.0 mg/L vincristine (VCR) for 24 h were analyzed by
      FCM for cell cycle. RESULTS: Sequence-specific siRNAs targeting MAD2
      significantly down regulated the expression of MAD2 in SGC7901 cells. In MAD2
      siRNA transfected cells, the rate of cell growth increased markedly and cell
      cycle couldn't be arrested in M phase induced by VCR, while the cells transfected
      with the mock vector could. CONCLUSION: Down regulation of MAD2 expression of
      SGC7901 bv sequence-specific siRNA could accelerate the cell growth and impair
      the mitosis arrest of SGC7901 induced by VCR.

PMID- 16643782
TI  - [Apoptin-induced apoptosis of human melanoma cells A375 via activation of caspase
      3].
AB  - AIM: To study whether apoptin gene induces apoptosis in human melanoma cells A375
      via the activation of caspase-3. METHODS: The human melanoma cells A375 were
      transiently transfected with recombinant pcDNAA3 plasmid, which contained apoptin
      gene, and the apoptosis was measured by DNA agarose electrophoresis, RT-PCR and
      flow cytometry. Caspase-3 relative activity was analyzed by colorimetric assay at
      various time. RESULTS: At 48 h after transfection, the apoptin gene could induce
      apoptosis of human melanoma cells A375 in vitro and the mRNA of apoptin gene
      could be detected by RT-PCR. Caspase-3 activity began to rise at 24 h after
      transfection and reached the peak at 72 h. CONCLUSION: Apoptin gene can induce
      apoptosis in human melanoma cells A375 via active caspase-3 and the activity of
      caspase-3 is time-dependent.

PMID- 16643783
TI  - [Influence of the peroxisome proliferator-activated receptor alpha on the
      development of T and B cells in mice].
AB  - AIM: To investigate the role of peroxisome proliferator-activated receptor a
      (PPARa) in the function and development of murine immune system. METHODS: Wild
      type and PPARa-null C57B/6 mice were sacrificed after 7-day dietary treatment of
      with peroxisome proliferator (PP). The changes in the weight of the thymus and
      spleen and cell numbers from the thymus and spleen were observed. The alterations
      of the cell phenotypes in bone marrow, thymus and spleen were determined by
      immunofluorescent staining using anti-mouse CD3, CD4, CD8a, CD19, IgM or
      CD45R/220 mAb through FACS analysis. The proliferation of T or B cells in
      response to ConA or LPS, respectively, was analyzed by 3H-TdR labeling. The PPARa
      mRNA expression in the bone marrow, thymus and spleen was examined by RT-PCR.
      RESULTS: PP treatment caused significant decreases in the weight and cell numbers
      of thymus and spleen and proliferative responsiveness of lymphocytes to ConA and
      LPS in wild-type mice, whereas these effects were significantly weaker in
      PPARalpha-null mice. The significant decreases of the CD4+ CD8+ population
      existed in the thymus and pro/pre-B cells and total B220+ cells in the bone
      marrow of wild-type mice with PP treatment, but not in PPARa-null mice.
      Interestingly, PPARalpha expression was detected in mouse thymus and spleen,
      rather than bone marrow. CONCLUSION: PPARalpha plays a major role in the PP
      induced immunomodulation, indirectly affecting the development of T and B cells.

PMID- 16643784
TI  - [Study of the construction and function of an eukaryotic expression plasmid of
      immunotoxin DT390 gene].
AB  - AIM: To construct a new recombinant eukaryotic expression plasmid of murine IFN
      gamma-inducible protein 10 (mIP10) gene and a truncated diphtheria toxin (DT390)
      gene and investigate its biological function. METHODS: mIP10 cDNA was cloned from
      murine liver tissue by RT-PCR and was inserted into eukaryotic expression plasmid
      SRalpha containing DT390 gene to construct plasmid SRalpha-DT390-mIP10. After
      being identified with restriction endonucleases digestion analysis and DNA
      sequencing, the recombinant plasmid was transfected into NIH3T3 cells through
      PolyFect. The expression of recombinant plasmid was detected by
      immunofluorescence assay and the bioactivity of mIP10-DT390 in cultured
      supernatant of the transfected NIH3T3 cells was detected by MTT colorimetry.
      RESULTS: A new recombinant immunotoxin expression plasmid SRalpha-DT390-mIP10 was
      constructed successfully and was expressed in NIH3T3 cells. The expressed DT390
      mIP10 killed the activated T cells effectively. CONCLUSION: A new recombinant
      eukaryotic expression plasmid SRalpha-DT390-mIP10 has been constructed and
      expressed successfully, which is useful in further studying the treatment of
      cancer and autoimmune diseases.

PMID- 16643785
TI  - [The changes of the thymocyte mitochondria mediated by nitric oxide in thymocyte
      apoptosis].
AB  - AIM: To study the changes of mitochondrial potential (delta psi m) and
      cardiolipin (CL) content during thymocyte apoptosis mediated by nitric oxide
      (NO). METHODS: SNAP was used as NO's donor to induce thymocyte apoptosis in mice
      and dexamethasone (DEX) was used as positive control drug. Three experiment
      groups were set, which were blank control group, SNAP group and DEX group. The
      ectropion of cell phosphatidylserine (PS) was detected by flow cytometry after
      stained with FITC-anti-annexin V mAb/PI. The changes of delta psi m and CL
      content during cell apoptosis were detected by DiOC6(3)/PE-anti-annexin V mAb and
      NAO/PE-anti-annexin V mAb, respectively. RESULTS: 6 hours after SNAP treatment,
      the thymocytes exhibited typical cell apoptotic characteristics and crenation
      appeared in most annexin V-positive cells. In DEX group, the delta psi m
      decreased and the rate of non-apoptotic cells was significantly higher than that
      in blank control group, but there was no significant difference between SNAP and
      control groups. 40%-50% of DiOC6(3)-negative cells in each group had the same
      size as normal cells. The percentage of the cells with reduced CL content in SNAP
      group was significantly higher than that in blank control group (P<0.01). Non
      apoptotic cells with reduced CL content were not found. In blank control group
      and SNAP group, percentage of normal-sized cells with reduced CL was (48.32+/
      3.96)% and (43.64+/-4.90)%, respectively. CONCLUSION: The process of thymocyte
      apoptosis mediated by NO in mice includes successively PS ectropion,
      mitochondrial depolarization, CL oxidation and cell crenation. As compared with
      DEX group, the mitochondrial change mediated by NO is a later event in cell
      apoptosis.

PMID- 16643786
TI  - [Inhibitory effect of CVB3-VP1 siRNA on CVB3 replication].
AB  - AIM: To inhibit the expression of CVB3 VP1 protein and the replication of CVB3
      with synthesized siRNAs. METHODS: According to the sequence and secondary
      structure of CVB3 VP1 protein, four pieces of siRNAs were designed following the
      requirement from Journal of Nature Cell Biology were synthesized in Shanghai
      GeneChem Company. Then they were transfected into HeLa cells by liposome
      (Lipofectamine 2000), but the non-transfected cells and non-specific siRNAs were
      taken as control. 48 hours later, the patho-morphous changes were observed, virus
      titer changes were examined by TCID50, CVB3-VP1 protein expression were detected
      by immunofluorescence with FITC dyeing, and CVB3-RNA level was tested by semi
      quantitative RT-PCR. RESULTS: Two pieces of the four specific synthesized siRNAs
      (VP1-1 and VP1-2) were found to have obvious inhibitory effect on CVB3
      replication and VP1 protein expression were reduced greatly. Besides, the changes
      of pathological cells were obviously mitigated. CONCLUSION: Specific siRNAs can
      effectively inhibit the expression of CVB3 VP1 protein and the replication of
      CVB3 in HeLa cells.

PMID- 16643787
TI  - [Inhibitory effect of blocking MaxiK channel on human monocyte-derived
      macrophages differentiation into foam cells].
AB  - AIM: To investigate the expression of high-conductance Ca2+-activated potassium
      channel (MaxiK channel) mRNA and protein during human monocyte-derived macrophage
      differentiation into foam cells and to study its function in foam cell formation.
      METHODS: Human peripheral blood monocytes were isolated from healthy male
      volunteers by density gradient centrifugation and then by adherent method. The
      obtained monocytes were cultured for 5 days to differentiate into macrophages.
      Based on establishment of human macrophage-derived foam cells model, the
      expression of MaxiK channel alpha-subunit was investigated by immunocytochemical
      staining, RT-PCR and Western blot. Furthermore, the effect of Paxilline, a MaxiK
      channel-specific inhibitor, on cholesterol metabolism in macrophages incepting
      oxidized low density lipoprotein (OxLDL) was studied. RESULTS: After the
      macrophages were co-incubated with 30 mg/L OxLDL at 37 degrees C for 60 hours,
      the cellular volume obviously enlarged and many red lipid granules were deposited
      in cytoplasm. The total amount of cholesterol (TC), free cholesterol (FC) and
      cholesterol ester (CE) in cells markedly increased and the ratio of CE/TC rose
      from (14.437+/-6.781)% to (57.946+/-3.507)% (n=7, P<0.05). However, the
      expression of MaxiK channel alpha-subunit had no significant change (P<0.05).
      Paxilline (5 micromol/L and 10 micromol/L) markedly reduced the content of TC, FC
      and CE in macrophages and the ratio of CE/TC decreased to (41.217+/-5.584)% (5
      micromol/L Paxilline) and (18.017+/-11.559)% (10 micromol/L Paxilline),
      respectively (n=7, P<0.05). Meanwhile, the red lipid granules deposited in the
      cytoplasm of macrophages also decreased. CONCLUSION: Blocking MaxiK channel can
      inhibit human monocyte-derived macrophage to be differentiated into foam cells.

PMID- 16643788
TI  - [The cytotoxicity and mechanism of CIK cells to breast cancer cells ZK-75-1].
AB  - AIM: To study the cytotoxicity and mechanism of cytokine-induced killer (CIK)
      cells to breast cancer cell line ZK-75-1. METHODS: The morphological changes of
      ZK-75-1 cells were observed by HE staining. The apoptosis of ZK-75-1 cell line
      was examined by TUNEL staining. The expression of P53, P16, C-myc, Bcl-2 and Bax
      was determined by immunocytochemical staining. RESULTS: The result of HE staining
      revealed that CIK cells moved toward the target cells, forming typical rosette
      cells. Granule-like substances appeared in cytoplasm of tumor cells, but only
      granule-shape patch was found in some tumor cells while breast cancer cells as
      control grew well. TUNEL staining indicated that the cells in control group were
      not stained or dyed well-distributed light blue. As the cells in experiment group
      became smaller, mucleoluser or perinuclear was dyed deep blue. The apoptotic rate
      of ZK-75-1 cells cocultured with CIK cells was increased after 4-12 hours and was
      decreased after 12-24 hours, with a significant difference compared with control
      group (P<0.01). Immunocytochemical staining showed that the expression of p53,
      p16, C-myc and Bcl-2 proteins in CIK group declined but the expression of Bax
      protein increased with the passage of time, which was significantly different
      compared with control (P<0.01). CONCLUSION: The mechanism of killing ZK-75-1
      cells by CIK cells is closely related to the downregulation of the expression of
      P53, P16, c-myc and Bcl-2 proteins and to the upregulation of the expression of
      Bax protein. It also has close relation with the time of exposure to CIK cells.

PMID- 16643789
TI  - [Effects of inosine injection in expression of myosin heavy chain in intrafusal
      and extrafusal myofibers in soleus muscle of tail-suspended rats].
AB  - AIM: To study the effects of inosine on myosin heavy chain (MHC) activity in rats
      soleus muscle after tail-suspension. METHODS: Weightlessness was simulated by
      tail-suspension of rats. Using immunohistochemistry technique, changes of
      expression of MHC in intrafusal and extrafusal fibers in soleus muscle were
      detected. RESULTS: Expression of fast MHC in intrafusal and extrafusal fibers in
      soleus muscle increased after 14 d of simulated weightlessness, whereas in tail
      suspended rats given inosine, the expression of fast MHC was not detected.
      CONCLUSION: Inosine could counteract the changes in expression of MHC in
      intrafusal and extrafusal fibers of rats soleus under simulated weightless
      situation.

PMID- 16643790
TI  - [Effects of cordyceps sinensis alcohol extractive on serum interferon-gamma level
      and splenic T lymphocyte subset in mice with viral myocarditis].
AB  - AIM: To investigate the effects of early application of cordyceps sinensis
      alcohol extractive (CSAE) on myocardial injury, level of serum IFN-gamma and
      splenic T lymphocyte subset in murine viral myocarditis (VMC). METHODS: 100 male
      BALB/c mice were divided randomly into control group (CG), infectious group (IG)
      and CSAE therapy group (CTG). Mice in IG and CTG were infected with Coxsackie
      virus B3 (CVB3). The 14-day survival rates and myocardial histopathology were
      observed. Serum IFN-gamma level was detected by ELISA and splenic CD3+, CD4+,
      CD8+ T lymphocytes were detected by flow cytometry. RESULTS: Serum IFN-gamma
      level and the percentage of splenic T lymphocyte subset in IG were decreased
      significantly, and CD4+/CD8+ T cell ratio increased significantly as compared
      with those of CG. Myocardial lesions in CIG were attenuated, while the 14-day
      survival of mice 85% (vs IG 55%, P<0.05), serum IFN-gamma and the percentage of
      splenic CD3+, CD8+ T lymphocytes in CTG were significantly higher than those in
      IG. There were no significant differences of the percentage of T lymphocyte
      subset and CD4+/CD8+ T cell ratio between CTG and CG. CONCLUSION: CSAE plays an
      important protective role against viral-induced murine myocarditis by inducing
      IFN-gamma and regulating T lymphocyte.

PMID- 16643791
TI  - [Expression of NF-kappaB/IkappaB signal pathway in renal tissues of hepatitis B
      virus-associated nephritis].
AB  - AIM: To investigate the expression of nuclear transcription factor-kappa B (NF
      kappaB)/IkappaB in renal tissues of hepatitis B virus-associated nephritis
      (HBVGN) and to study its role in the pathogenesis of HBVGN. METHODS: The
      expression of NF-kappaB p65 and IkappaB-alpha in renal tissues was examined in
      biopsy specimens from 42 HBVGN patients, 20 patients with primary membranous
      nephropathy and 5 normal subjects by immunohistochemical staining. RESULTS: The
      NF-kappaB p65 expression in glomerular and tubular of HBVGN tissues was notably
      higher than that in normal control tissues (P<0.05) and in primary membranous
      nephropathy tissues (P<0.01). The IkappaB-alpha expression in glomerular and
      tubular of HBVGN tissues was lower than that in primary membranous nephropathy
      tissues (P<0.05). CONCLUSION: There might be protein degradation of IkappaB-alpha
      and nuclear translocation of NF-kappaB in renal tissues of HBVGN, which suggests
      that NF-kappaB/IkappaB signal pathway may play an important role in the
      pathogenesis of HBVGN.

PMID- 16643792
TI  - [Establishment of immortalized B lymphoblast cell line from patients with chronic
      hepatitis B].
AB  - AIM: To establish immortalized B lymphoblast cell line (BLCL) from patients with
      chronic hepatitis B (CHB) in vitro. METHODS: The peripheral blood mononuclear
      cells (PBMC) were isolated from the patients with CHB by routine method and
      incubated with EB virus (EBV) in the presence of CpG DNA motifs and cyclosporin A
      (CysA) for about 28 days. Morphological characteristic of the established
      immortalized BLCL was observed by microscope and the expression of CD19 and CD23
      on cellular surface was determined by flow cytometry. RESULTS: BLCL was
      successfully established and could be cultured and propagated for a long time in
      vitro. CONCLUSION: EBV-immortalized BLCL provides a resource of target cells for
      further research on the cellular immunity of patients with CHB.

PMID- 16643793
TI  - [Effects of PMA on CD147 expression in cultured THP-1 cells and monocytes of RA
      patients].
AB  - AIM: To investigate the expression of CD147 both on cellular membrane and in
      culture supernatant of in vitro cultured THP-1 cells and monocytes of RA patients
      before and after stimulation with phorbol myristate acetate (PMA). METHODS: Human
      peripheral blood monocytes (HPBMs) were segregated from RA patients by adherent
      culture method. After the HPBMs and THP-1 cells were stimulated with PMA, the
      expression rate and expression intensity of CD147 on THP-1 cells and HPBMs of RA
      patients were determined by flow cytometry. The soluble CD147 levels in culture
      supernatant of in vitro cultured THP-1 cells and HPBMs were quantified by double
      antibody Sandwich ELISA. RESULTS: The soluble CD147 in the supernatant of
      cultured THP-1 cells and HPBMs was detectable before PMA stimulation. Both cells
      showed high CD147 expression. After PMA stimulation, soluble CD147 level in the
      supernatant of THP-1 cells increased. CD147 expression on THP-1 cells firstly
      increased then decreased and kept stable for several days. CD147 expression on
      HPBMs of RA patients decreased, but CD147 level in the culture supernatant of
      HPBMs of RA patients increased and kept stable for 2 days. CONCLUSION: CD147
      molecule can be shed from the membrane of THP-1 cells and HPBMs of RA patients,
      or it can be directly secreted into the culture supernatant from the two kinds of
      cells. PMA can up-regulate the level of soluble CD147.

PMID- 16643794
TI  - [Detection of HCV antigen in the serum by immunodotting].
AB  - AIM: To set up a simple and rapid screening method of early detection for HCV
      infection. METHODS: The HRP-anti-HCV monoclonal antibodies (mAbs) conjugate was
      prepared by anti-HCV-core and anti-HCV-NS3 mAb with high specificity. HCV
      antigens in the sera from hepatitis patients and normal persons were detected by
      immunodotting and compared by double antibody ELISA and RT-PCR. RESULTS: The
      positive ratio for HCV antigen was 15.4% (8/52), 1.73% (19/1099) and 1.03% (1/97)
      in hepatitis C patients, hepatitis B patients and hepatitis NA-NE patients,
      respectively. The results for HCV antigen were negative in hepatitis A patients
      (0/81), hepatitis E patients (0/67) and normal persons (0/50). There was no
      significant difference among the immunodotting and double antibody ELISA and RT
      PCR. There was definite correlation between the immunodotting and RT-PCR.
      CONCLUSION: This method, simple and rapid with high specificity, provides an
      effective way for the early diagnosis and routine detection of HCV.

PMID- 16643795
TI  - [Expression, purification and immunogenicity of a novel hepatitis E virus-like
      particle].
AB  - AIM: To express and characterize a novel hepatitis E virus (HEV) recombinant
      protein which contains HEV neutralization epitope(s). METHODS: The gene fragment
      encoding for amino acid 452-617 of HEV open reading frame 2 protein (pORF2) was
      inserted into the plasmid pET28a(+). The recombinant plasmid was used to
      transform the E. coli BL21(DE3) strain. The recombinant protein was expressed by
      IPTG induction, purified by Ni-NTA chromatography and analyzed by SDS-PAGE,
      Western blot and electronmicroscopy. Immune responses to the recombinant protein
      were determined by the immunization of mice. RESULTS: The expressed HEV
      recombinant protein was in a naturally-soluble form with a molecular weight of
      22,000. The protein assembled into a virus like particle (VLP) with a diameter of
      approximate 20 nanometers. Moreover, this novel protein was reactive to serum
      samples obtained from the patients with HEV infection. After the mice were
      immunized with the protein, they developed anti-HEV antibodies which could
      neutralize HEV infection in cell culture. CONCLUSION: An E. coli-expressed
      recombinant protein containing 166 amino acid of HEV pORF2 can form VLP with good
      immunogenicity and antigenicity. This novel HEV VLP is valuable for the
      development of HEV vaccine and new diagnostic kit.

PMID- 16643796
TI  - [The effect of HCV core protein on the expression of cyclooxygenase 2 (COX-2) in
      HepG2 cells].
AB  - AIM: To investigate the effect of Hepatitis C virus (HCV) core protein on the
      expression of cyclooxygenase 2 (COX-2). METHODS: The genes encoded HCV core
      protein were amplified from plasmid containing full length genome of HCV strain
      H77 using PCR, and were cloned into eukaryotic expression vector pcDNA3.1. The
      recombinant HCV-C/pcDNA3.1 was transiently co-transfected into HepG2 cells with
      luciferase reporter vector containing COX-2 promotor (COX2pro1.5 kb/luc). The
      luciferase activity and COX-2 protein expression were detected. RESULTS: The
      recombinants HCV-C/pcDNA3.1 have been constructed successfully. The luciferase
      activity of COX-2 promotor was activated by the expressed HCV core, and the
      increased protein expression of COX-2 in transfected HepG2 cells was detected by
      Western blot. CONCLUSION: HCV core protein can activate the COX-2 promotor and
      induce its expression, which provides a new experimental basis for further
      research on relationship between COX-2 and HCV pathogenesis.

PMID- 16643797
TI  - [Effect of cyclosporin A on the production of IFN-gamma by murine splenocytes].
AB  - AIM: To explore the effect of cyclosporine A (CsA) on the production of IFN-gamma
      by murine splenocytes after stimulation with different reagents. METHODS: Mouse
      splenocytes were prepared and cultured with anti-CD3 mAb alone, anti-CD3 mAb plus
      anti-CD28 mAb or anti-CD3 mAb plus IL-12, in the presence or absence of different
      concentrations of CsA. After stimulating for 3 days, the content of INF-gamma in
      the culture supernatant was assayed by ELISA. The effects of CsA on the
      expression of activated molecules on T cells and intracellular IFN-gamma
      production were examined at the single cell level by flow cytometry. RESULTS: The
      mouse splenocytes stimulated with anti-CD3 mAb, anti-CD3 mAb + anti-CD28 mAb or
      anti-CD3 mAb + IL-12 could produce high level of IFN-gamma, but CsA inhibited INF
      gamma production in a dose-dependent manner. The inhibitory mechanism of CsA was
      related to the activation of splenocytes. CONCLUSION: CsA can inhibit the
      expressions of CD25 and CD69 on splenocytes, as well as INF-gamma production by
      splenocytes in a dose dependent manner.

PMID- 16643798
TI  - [Effects of estradiol intervention on peripheral blood CD90+ cells and cardiac
      function in de-ovary rats before and after myocardial infarction].
AB  - AIM: To investigate the effects of estradiol intervention on peripheral blood
      CD90+ cells and cardiac function in de-ovary rats before and after myocardial
      infarction. METHODS: Thirty SD female rats were divided into the control group,
      acute myocardial infarction group, de-ovary myocardial infarction group, de-ovary
      replacement group with estradiol, and de-ovary therapy group with estradiol.
      CD90+ cell percentage was determined with flow cytometry. The left ventricle end
      systolic pressure (LVESP), left ventricle end diastolic pressure (LVEDP),
      +dp/dt(max) and -dp/dt(max) were also measured with the POWERLAB4.12 system.
      RESULTS: The percentage of peripheral blood CD90+ cells in the de-ovary
      myocardial infarction group was remarkably lower than that in the acute
      myocardial infarction group and the de-ovary replacement group with estradiol
      (P<0.01). In the de-ovary replacement group with estradiol, the percentage of
      peripheral blood CD90+ cells was remarkably elevated following the first day of
      operation (P<0.05), reaching the peak value at day 3. In the de-ovary therapy
      group with estradiol, it started to elevate at day 7 after the operation, much
      lower than that in the de-ovary replacement group with estradiol. LVESP in each
      operation group decreased, especially in the acute myocardial infarction group,
      whereas LVEDP increased in the de-ovary group and de-ovary therapy group with
      estradiol (P<0.01). CONCLUSION: Replacement with estradiol before myocardial
      infarction exerts more beneficial effects than estradiol replacement after
      myocardial infarction in de-ovary rats.

PMID- 16643799
TI  - [The effects of Th1/Th2 cells on in vitro expansion and colony forming of CD34+
      cells of aplastic anemic patient].
AB  - AIM: To investigate the effects of both Th1/Th2 imbalance and its re-attainment
      on in vitro expansion and hematopoiesis of CD34+ cells from a severe aplastic
      anemia (sAA) patient. METHODS: A preliminary-diagnosed sAA patient was studied.
      (1) Bone marrow mononuclear cells (BMMNC) were isolated and CD34+ and CD4+ cells
      were enriched by magnetic beads respectively. (2) The Th1/Th2 cell ratio within
      CD4+ subset was detected by flow cytometry (FCM). (3) Enriched-CD34+ cells were
      expanded and re-enriched for enough cells to be divided into four groups:
      control, Th cell treatment, Th cell and IFN-gamma treatment, and Th cell and IL-4
      treatment, respectively. (4) After expansion for 10 d, colony-forming unit assay
      was performed on cells in each group. (5) Patient's Th1/Th2 ratio was followed up
      by FCM after immunotherapy. RESULTS: (1) Symptom remission was achieved after
      therapy for 5 months. (2) Th1/Th2 cell ratio of the patient before and after
      remission was 22.47 and 12.27, respectively, while that of healthy controls was
      8.98+/-4.45. (3) The CD34+ cell expansion rates as well as CFU numbers, from high
      to low, were ranked as control, Th cell and IL-4 contained group, Th cell
      contained, and Th cell and IFN-gamma contained group. CONCLUSION: Predominant Th1
      cells seem to directly inhibit the self-renewal, proliferation and lineage
      differentiation of CD34+ cells in vitro, which can be counteracted by IL-4,
      probably mediated by switching Th1/Th2 balance.

PMID- 16643800
TI  - [Cloning, expression and identification of recombinant fusion protein GX1
      rmhTNFalpha].
AB  - AIM: To construct prokaryotic vector GX1-rmhTNF containing neovascular-targeting
      peptide GX1 and human TNFalpha and produce the GX1-rmhTNF protein. METHODS: We
      have previously obtained a specific phage peptide CGNSNPKSC (GX1) binding to
      vasculature of human gastric cancer. The GX1-rmhTNFalpha vector was constructed
      by merging sequence of neovascular-targeting peptide GX1 with N-terminal of new
      recombined human TNFalpha (rmhTNFalpha) using gene engineering methods. The
      expression of the fusion protein GX1-rmhTNFalpha in E. coli was induced by
      temperature. The expression of GX1-rmhTNFalpha was detected by SDS-PAGE and
      Western blot. RESULTS: A novel protein with expected molecular mass about 18,000
      was found after SDS-PAGE and gel staining. The expressed product showed a good
      binding ability to anti-TNFalpha monoclonal antibody. CONCLUSION: The prokaryotic
      vector GX1-rmhTNF was constructed and the expression of GX1-rmhTNF protein was
      successfully induced, which was helpful for further purification of GX1-rmhTNF
      protein.

PMID- 16643801
TI  - [Construction and expression of chimeric anti-human CD20 monoclonal antibody].
AB  - AIM: To construct the eukaryotic expression vector of chimeric anti-human CD20
      monoclonal antibody (mAb) and realize its expression. METHODS: The light- and
      heavy-chain genes were amplified from hybridoma cell line 1-28 secreting anti
      human CD20 mAb by RT-PCR and were cloned to T vector and sequenced. Proteins of
      mAb 1-28 were separated by reducing SDS-PAGE. Light- and heavy-chain bands were
      excised from preparative gel, digested by trypsin, and subjected to peptide mass
      fingerprinting. Software Biolynx and pepeseq were used to evaluate the score of
      probability. Correctness of the light- and heavy-chain DNA sequences was verified
      by their protein sequences. Genes of V(H) and V(L) were amplified from T vector
      and cloned into chimeric antibody expression vector (pCMV-V(H) and pCMV-V(L)),
      generating the expression vectors of chimeric anti-human CD20 mAb (C1-28)
      including light chain expression vector C1-28L and heavy chain expression vector
      C1-28H. The two plasmids were co-transfected into 293T cells with Lipofectamine
      2000. RT-PCR was used to detect the transcription at mRNA level. C1-28 expression
      was detected by Sandwich ELISA and Western blot methods. RESULTS: mAb 1-28's
      genes were successfully cloned and verified by peptide mass fingerprinting.
      Eukaryotic expression vectors of anti-human CD20 mAb were constructed and
      expressed in 293T cells with the expression amount reaching 257 mg/L and the
      molecular weight consistent with that of human IgG. CONCLUSION: These experiments
      lay solid foundation for further study on the role of chimeric CD20 antibody in
      the treatment of non-Hodgkin's lymphoma.

PMID- 16643802
TI  - [Preparation and characterization of anti-morphine vaccine antibody].
AB  - AIM: To prepare anti-morphine vaccine antibody with high titer and good
      specificity and to identify its properties. METHODS: Chemically synthesized 6
      succinylmorphine (M-6-S) was cross-linked to BSA in pH 9.0 carbonate buffer.
      After being purified by gel filtration and (NH4)2SO4 salting out, the immunogen
      was used to immunize BALB/c mice and SD rats. The titer and specificity of
      antisera were identified by ELISA and neutralization inhibition test,
      respectively. The effect of the immunization was examined by the radiant heat
      tail-flick (TF) reflex test. RESULTS: The titers of antiserum from immunized
      BALB/c mice and SD rats were up to 1:200,000 and over 1:20,000, respectively.
      Neutralization inhibition test proved that the anti-morphine vaccine antibody had
      the cross-reactions to following drugs with analogous structure as morphine: 6
      monoacetylmorphine, heroin and codeine. The TF reflex test showed: (1) TF
      reflexes were notable inhibited after intraperitoneal injection of 2 mg/kg
      morphine, and (2) percentage of the maximum possible effect (% MPE) reduced
      74.7%, (3) the TF latency recovered to the baseline level much more rapidly
      compared with the control rats. CONCLUSION: The M-6-S-BSA vaccine has been
      prepared successfully. The BALB/c mice and SD rats immunized with the vaccine can
      produce anti-morphine antibody with high titer and satisfactory specificity,
      which may significantly reduce rats' antinociception against morphine.

PMID- 16643803
TI  - [Expression of mouse lipopolysaccharide response protein LRP in E. coli and
      preparation of rabbit anti-mLRP serum].
AB  - AIM: To express mouse lipopolysaccharide response protein (mLRP) and prepare
      rabbit anti-mLRP serum. METHODS: The predicted mouse lrp cDNA sequence was
      obtained by splicing homologous ESTs by comparing human lrp cDNA with mouse ESTs.
      Then the primers were designed. mlrp cDNA from NIH3T3 cells stimulated with
      lipopolysaccharide (LPS) was amplified by RT-PCR and was cloned into prokaryotic
      expression vector pTAT to construct recombinant expression vector pTAT-mlrp. The
      His-TAT-mLRP fusion protein was expressed in E. coli BL21(DE3) and was used to
      immunize the rabbits to get rabbit anti-mLRP serum. The anti-serum was purified
      by the acetone precipitation method. The specificity of the rabbit anti-mLRP
      serum was determined by Western blot. RESULTS: The predicted length of mlrp cDNA
      was 1905 bp. The encoding region of the cloned mlrp cDNA, 1554 bp, was inserted
      into pTAT. The His-TAT-mLRP fusion protein was expressed successfully in E. coli.
      The rabbit anti-mLRP serum was prepared by immunizing the rabbit with mLRP
      protein. CONCLUSION: The successful expression of mLRP and the preparation of
      rabbit anti-mLRP serum lays the foundation for further study of the function of
      mLRP.

PMID- 16643804
TI  - [Preparation and characterization of monoclonal antibody against Vibrio cholerae
      O139].
AB  - AIM: To prepare monoclonal antibody (mAb) against Vibrio cholerae O139, which
      would be used as the gold colloidal reagent strip for rapid detection of O139,
      and to determine its biological characterization. METHODS: BALB/c mice were
      immunized by inactivated Vibrio cholerae O139. Anti-O139 mAbs were prepared by
      using hybridoma technique. The specificity of mAb was determined by indirect
      ELISA and Western blot. The indirect ELISA was used to identify Ig subgroup,
      detect its titer in ascites and relative affinity, and analyze antigen-binding
      epitope of mAbs. RESULTS: Two hybridoma cells (O4D7 and O4D10), secreting anti
      O139 mAbs were obtained. The Ig subgroups of O4D7 and O4D10 were IgG2b and IgG3,
      respectively. The mAb's titer in ascites was 1:10(7). The relative affinity of
      mAb O4D7 was more than 10(5) and that of O4D10 was more than 10(4). The result of
      additive ELISA showed that two mAbs could recognize different antigen epitopes.
      CONCLUSION: The successful preparation of two anti-O139 mAbs provides a powerful
      tool for the development of a rapid method of detecting Vibrio cholerae O139
      infection.

PMID- 16643805
TI  - [Preparation and characterization of monoclonal antibody against DCXR].
AB  - AIM: To prepare monoclonal antibodies (mAbs) against Dicarbonyl/L-xylulose
      reductase (DCXR). METHODS: Normal human liver tissues were homogenized, and
      mitochondria were isolated by differential centrifugation. The total
      mitochondrial proteins were used to immunize BALB/c mice to prepare mAbs by
      routine hybridoma technique. The mAbs were detected by ELISA, Western blot and
      immunohistochemistry. The antibody specificities were identified by mass
      spectrometry (MS) following immunoprecipitation (IP) and confirmed by Uni-ZAP
      expression library screening. RESULTS: One clone of hybridoma AFF091 secreting
      specific mAb against DCXR was obtained. The Ig subclass of the mAb was IgG1 and
      it can be used in ELISA, Western blot, immunohistochemistry, and
      immunoprecipitation. CONCLUSION: A hybridoma cell line stably secreting specific
      mAb against DCXR was established. The specific mAb against DCXR would be very
      useful for investigation of DCXR functions and distribution.

PMID- 16643806
TI  - [Application of vital dye CFDA-SE and SNARF-1 to evaluate mixed lymphocyte
      reaction].
AB  - AIM: To establish a new method for more comprehensive evaluation of responsive
      intensity in one-way mixed lymphocyte reaction (MLR). METHODS: CFDA-SE labeled
      lymphocytes from lymph nodes of BALB/cJ mice were applied as responder cells, and
      SNARF-1 labeled splenocytes from BALB/cJ or C57BL/6 mice which had been
      pretreated with mitomycin C were applied as stimulator cells to establish mixed
      lymphocyte culture (MLC). After 96 h of culture, cells were harvested and
      analyzed by flow cytometry to acquire the proliferative information of SNARF-1
      negative and CFSE positive staining responder cells. ModFit software was then
      used to get more proliferation related index. RESULTS: With increasing division
      cycles, the CFSE fluorescence was diluted to the extent that the responder cells
      could not be discriminated from stimulator cells, which was resolved by gating
      SNARF-1 positive cells out to define responder cells. Several important
      proliferation related indexes were obtained by ModFit software, such as precursor
      frequency and proliferation index, etc. CONCLUSION: Our results show that
      application of vital dye CFDA-SE and SNARF-1, combined with flow cytometry is a
      powerful tool for evaluation of responsive intensity in one-way MLR.

PMID- 16643807
TI  - [Methodological study on magnetic enzymic immunoassay for detecting free hCGbeta
      subunit].
AB  - AIM: To establish a novel magnetic enzyme immunoassay (MEIA) for detecting human
      choriogonadotropin free beta subunit (hCGbeta). METHODS: Two monoclonal
      antibodies (mAb) were used for conjugating with FITC and with alkaline
      phosphatase(AP) respectively, which incorporated magnetic solid phase separation.
      Magnetic beads were coupled with sheep anti-FITC antibody as solid phase, and
      phenolphthalein monophosphate was used as substrate to set up MEIA for detecting
      hCGbeta. RESULTS: The sensitivity of hCGbeta MEIA kit reached 0.1 IU/L. The
      intraassay variation and inter-assay variation was 8.5% and 14% respectively,
      with the average recovery rate of dilution of 92.5%. The kit showed no cross
      reactivity to LH, TSH and FSH, while a cross reactivity of 1.2% to intact hCG at
      concentration of 1000 IU/L. The time of efficacy of hCGbeta MEIA kit was longer
      than 14 months. CONCLUSION: hCGbeta MEIA kit is better than hCGbeta radio
      immunoassay and ELISA kit, which can provide a high-qualitative and cheap hCGbeta
      kit for market.

PMID- 16643808
TI  - [Chemiluminescent detection of E. coli O157:H7 in food based on magnetic enzyme
      linked immuno method].
AB  - AIM: To establish a new chemiluminescent assay with high sensitivity for
      detecting E. coli O157:H7 in food. METHODS: The assay was established based on
      the alkaline phosphatase (ALP) labeled anti-E. coli O157:H7 antibody, which
      reacted with an excellent chemiluminescent reagent, 3(2' spiroadamantane)4
      methoxy 4(3''phosphoryloxy) phenyl 1,2 dioxetane (AMPPD) buffer solution and
      emitted the photons. RESULTS: The sensitivity of chemiluminescence assay was 850,
      and the linear range was 1000-50,000. The intra- and interassay CV values (CVs)
      were respectively below 15% and 20%. The correlation coefficient was 0.9807 by
      comparing with the conventional counting method. CONCLUSION: The chemiluminescent
      immunoassay is more accurate than other methods in the detection of concentration
      of E. coli O157:H7 in samples.

PMID- 16643809
TI  - [Secretory expression of sCD14 in Pichia pastoris and its LPS binding activity].
AB  - AIM: To achieve secretory expression of mature sCD14 gene in Pichia pastoris and
      to analyze its LPS binding activity. METHODS: sCD14 gene was cloned into yeast
      expression vector pPIC9K. Recombinant plasmid was lineared by Sac I and
      transformed into Pichia pastoris GS115. Positive integrated clones were screened
      and expressed by methanol inducing. RESULTS: The mature sCD14 was expressed in
      BMMY with pH 6.5 after optimization of inducing expression condition. Western
      blot and ELISA data revealed recombinant products combined with specific
      antibody. The results from FACS showed recombinant product had biological
      activity of binding with LPS. CONCLUSION: The recombinant mature sCD14 molecules
      with favorable LPS-binding activity could be used for further study on its
      structure and functions.

PMID- 16643810
TI  - [Insulin prevents injury and enhances survival of rat hepatocytes via its anti
      inflammatory effects].
AB  - AIM: To investigate whether insulin exerts protective effects against hepatocytes
      injury indirectly induced by LPS and if so, the mechanism involved. METHODS:
      Kupffer cells and hepatocytes were isolated from male Sprague-Dawley rats by
      pronasecollagenase perfusion and cultured. Kupffer cells were stimulated by
      lipopolysaccharide (LPS) or LPS+insulin for 4 h, the supernatant of different
      groups were collected to detect TNF-alpha and IL-10 by ELISA and to stimulate the
      primary cultured rat hepatocytes with or without anti-TNF-alpha antibody. After
      the hepatocytes were stimulated for 12 h, cell survival rate and injury indexes
      were detected. RESULTS: (1) The supernatant of LPS-activated Kupffer cells caused
      significant hepatocytes injury. Treatment with insulin produced a potent
      protective effect as evidenced by decreased ALT and AST levels (P<0.01, n=8) and
      improved hepatocytes survival rate (P<0.01, n=8). (2) Compared with the LPS
      group, insulin significantly decreased TNF-alpha secretion (P<0.01, n=8) and
      increased IL-10 secretion (P<0.05, n=8) from Kupffer cell stimulated by LPS. (3)
      Incubating hepatocytes with anti-TNF-alpha antibody attenuated hepatocytes injury
      induced by the supernatant of LPS-activated Kupffer cells. But treatment with
      anti-TNF-alpha antibody and insulin did not exert additive effect compared with
      treatment with insulin alone. CONCLUSION: Insulin has protective effects on rat
      hepatocytes injury indirectly induced by LPS, which is associated with
      suppression of the pro-inflammatory cytokine TNF-alpha and increment of the anti
      inflammatory cytokine IL-10 both from Kupffer cells.

PMID- 16643811
TI  - Effect of face familiarity on age decision.
AB  - The present experiment was planned to check whether the extraction of apparent
      age is affected by face identity (familiarity) or not. According to the
      traditional view, age estimation should be carried out independently of face
      identity, because it is one of the visually derived semantic codes (like gender
      and ethnicity). However, little is known about its underlying mechanisms.
      Moreover, some recent studies have cast doubt on the parallel thesis regarding
      facial expression, facial speech, ethnicity, and gender. Given the promising
      results of a pilot experiment (n=24), 16 Caucasian participants were enrolled in
      an "age decision" task on morphed faces derived from one old and one young source
      face, in the proportion 70:30. The respondents had previously been familiarised
      with half the source faces by a learning procedure (associating the face,
      surname, occupation and city of residence of the person displayed), while the
      remaining half were unfamiliar. The results showed that age decision was affected
      by face familiarity, at least when the task was perceptually difficult enough.
      This adds support to the thesis that the identification of identity and the
      extraction of visually derived semantic codes are not made independently from
      each other. The status of age, within the visually derived semantic codes, is
      also discussed.

PMID- 16643812
TI  - Is there a useful cesarean birth measure? Assessment of the nulliparous term
      singleton vertex cesarean birth rate as a tool for obstetric quality improvement.
AB  - OBJECTIVE: This study was undertaken to assess the utility of the nulliparous
      term singleton vertex cesarean birth (NTSV CB) measure as a quality improvement
      tool for use at the hospital level. STUDY DESIGN: We prospectively collected data
      on all NTSV births in Sutter Health's 20 birthing units over a 3-year period,
      2001 through 2003, totaling 41,416 births. Hospital rates of NTSV CB, obstetric
      practices, and infant outcomes were calculated and compared by using weighted
      logistic analyses. In addition, we examined the effect of maternal age on the
      NTSV CB measure by using direct standardization with US norms for nulliparous
      women. RESULTS: There was large variation noted in the NTSV CB rate among the 20
      hospitals, with unadjusted rates ranging from 10.5% to 30.2%. Strong correlations
      were found between CB rates and labor induction rates (r = 0.57, P < .0001) and
      with early labor admission rates (r = 0.62, P < .0001). The strongest correlation
      was found between NTSV CB rates and a combined measure of induction and early
      labor admission (r = 0.73, P < .0001). Rates of term 5-minute Apgar score below 7
      were not correlated with the NTSV CB rate. Hospital nulliparous maternal age
      distribution varied markedly and direct standardization led to significant
      changes in the NTSV CB rate. CONCLUSION: NTSV CB rate is strongly influenced by
      elective obstetric practices. The addition of an easily performed maternal age
      adjustment makes it the most promising CB quality measure for use at the hospital
      level.

PMID- 16643813
TI  - Thromboxane mediates neutrophil superoxide production in pregnancy.
AB  - OBJECTIVE: We recently reported that activation of neutrophils obtained from
      pregnant women resulted in production of tumor necrosis factor-alpha by a
      thromboxane- and cyclooxygenase-2- dependent mechanism. Activated neutrophils
      also generate reactive oxygen species such as the superoxide anion, which can
      lead to oxidative damage of biomolecules. In this study, we tested the
      possibility that thromboxane plays a role in neutrophil superoxide generation in
      pregnancy via cyclooxygenase-2 by inhibiting key enzymes in the pathway leading
      to its synthesis. STUDY DESIGN: Neutrophils were isolated from normal pregnant
      women and incubated for 2 hours in phosphate-buffered saline with glucose alone
      or with treatments. Experiment 1 treatments were: (1) indomethacin at a dose
      sufficient to inhibit phospholipase A2 (100 microM); (2) aspirin (100 microM), a
      cyclooxygenase-1 and cyclooxygenase-2 inhibitor; (3) NS-398 (10 microM), a
      specific cyclooxygenase-2 inhibitor; (4) nordihydroguaiaretic acid (10 microM), a
      lipoxygenase inhibitor; and (5) pinane thromboxane, a thromboxane synthase
      inhibitor. Experiment 2 treatments were arachidonic acid (50 microM and 100
      microM) and arachidonic acid (100 microM) alone or in combination with phorbol
      myristic acid plus varying doses of pinane thromboxane (5 microM to 100 microM).
      RESULTS: Indomethacin inhibited superoxide production to one fourth of control.
      Aspirin, NS-398, and pinane thromboxane also significantly decreased neutrophil
      superoxide production. Nordihydroguaiaretic acid had no significant affect on
      neutrophil superoxide generation. Arachidonic acid stimulated superoxide
      generation by neutrophils, and this was inhibited by pinane thromboxane in a dose
      dependent manner. Pinane thromboxane also significantly inhibited superoxide
      production by neutrophils exposed to arachidonic acid plus phorbol myristic acid,
      a known activator of neutrophils. CONCLUSION: These data demonstrate that
      thromboxane is involved in the production of superoxide by neutrophils obtained
      from pregnant women. Neutrophil superoxide generation is significantly decreased
      by inhibition of thromboxane synthase, cyclooxygenase-2, or phospholipase A2. NS
      398 inhibits neutrophil superoxide generation as effectively as aspirin,
      suggesting that cyclooxygenase-2 plays an important role in neutrophil superoxide
      production mediated by thromboxane.

PMID- 16643815
TI  - Is resectoscopic treatment of atypical endometrial polyps a safe option?
AB  - OBJECTIVE: This study was undertaken to evaluate the long-term efficacy and
      prognosis of hysteroscopic resection and coagulation of the polyp base of
      endometrial polyps with focal atypia in postmenopausal women. STUDY DESIGN: In
      this observational noncomparative study, conservative treatment was offered to 16
      patients, with high anesthesiologic risk, who had endometrial polyps with focal
      atypia and a surrounding atrophic endometrium. To confirm the focality of the
      lesion, the polyps were analyzed separately from their bases. Patients with
      atypia in the polyp base were excluded. RESULTS: After 5 years of follow-up, 13
      patients are disease free, 2 underwent vaginal hysterectomy and annessiectomy due
      to other causes, and 1 died for cardiac disorders. CONCLUSION: Adenomatous polyps
      with atypia can be treated resectoscopically if the treatment is associated with
      an accurate histologic examination of the polyp base and its eventual involvement
      and the features of the remaining uterine mucosa. A thorough follow-up is
      recommended. Studies on wider casuistries of patients are needed.

PMID- 16643816
TI  - Obstetric outcomes in women with elevated maternal serum human chorionic
      gonadotropin.
AB  - OBJECTIVE: This study was undertaken to assess outcomes in unselected women with
      maternal serum human chorionic gonadotropin (MShCG) 2.0 MoM or greater. STUDY
      DESIGN: This is an observational cohort study of 309 women with MShCG 2 MoM or
      greater and 309 women of the same age and ethnicity with MShCG less than 2.0 MoM
      who were evaluated for preterm delivery (PTD), preeclampsia, stillbirth, birth
      weight 10% or less, and birth weight 90% or greater (larger for gestational age
      [LGA]). Confounding variables evaluated were nulliparity, prior PTD, chronic
      hypertension, diabetes, and maternal serum alpha-fetoprotein and estriol.
      RESULTS: There was no overall increase in adverse outcomes despite associations
      found with PTD for preeclampsia with MShCG 3.0 MoM or greater (odds ratio [OR]
      5.9, CI 1.5-23.2) and PTD for fetal indications with MShCG 4.0 MoM or greater (OR
      45.5, CI 4.1-509). There was an increase of LGA infants with MShCG 3.0-3.9 MoM
      (OR 2.5, CI 1.0-5.8). CONCLUSION: Adverse pregnancy outcome is associated with
      MShCG 3.0 MoM or greater, thus increased surveillance is not warranted with lower
      values.

PMID- 16643817
TI  - Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular
      endothelial growth factor in women with abnormal uterine artery Doppler and in
      those with fetal growth restriction.
AB  - OBJECTIVE: This study was undertaken to determine whether maternal serum
      concentration of the angiogenic factor vascular endothelial growth factor (VEGF)
      and its circulating antagonist, soluble fms-like tyrosine kinase 1 (sFlt-1),
      which have been implicated in the pathogenesis of preeclampsia (PE), are altered
      in pregnancies that subsequently develop PE and in those with established fetal
      growth restriction (FGR). STUDY DESIGN: Three groups of healthy pregnant women at
      23 to 25 weeks of gestation were examined: group A (n = 42) with normal uterine
      artery Doppler waveforms, group B (n = 49) with abnormal uterine artery Doppler
      waveforms, and group C (n = 15) with abnormal Doppler results and established
      FGR. Comparisons between multiple groups were performed by using 1-way analysis
      of variance or Kruskal-Wallis test. RESULTS: In group C, compared with group A,
      the median sFlt-1 was significantly higher (P < .0001) and VEGF was lower (P <
      .001). Group C included 3 women who had PE develop. In group B, 19 women had a
      normal outcome, 13 had PE develop, and 17 had FGR develop. There were no
      significant differences in sFlt-1 levels between any of the subgroups of group B
      and group A. CONCLUSION: Maternal serum concentration of sFlt-1 in pregnancies
      with FGR is increased but this increase is not evident in pregnancies with
      impaired placentation that subsequently had either FGR or PE develop.

PMID- 16643818
TI  - Corticosteroids and HELLP.

PMID- 16643820
TI  - Prospective risk of intrauterine death of monochorionic-diamniotic twins.
AB  - OBJECTIVE: The purpose of this study was to calculate the prospective risk of
      fetal death in monochorionic-diamniotic twins. STUDY DESIGN: We evaluated 193
      monochorionic diamniotic twin pregnancies that were followed and delivered after
      24 weeks. Surveillance included cardiotocography and sonography performed at
      least once weekly. The prospective risk of fetal death was calculated as the
      total number of deaths at the beginning of the gestational period divided by the
      number of continuing pregnancies at or beyond that period. RESULTS: The fetal
      death rate was 5 of 193 pregnancies (2.6%; 95% CI, 1.1, 5.9); the prospective
      risk of stillbirth per pregnancy after 32 weeks of gestation was 1.2% (95% CI,
      0.3% - 4.2%). CONCLUSION: Under intensive surveillance, the prospective risk of
      fetal death in monochorionic-diamniotic pregnancies after 32 weeks of gestation
      is much lower than reported and does not support a policy of elective preterm
      delivery.

PMID- 16643821
TI  - Urinary incontinence and pelvic floor dysfunction in Asian-American women.
AB  - OBJECTIVE: The objective of the study was to describe the prevalence, risk
      factors, and impact of urinary incontinence and other pelvic floor disorders
      among Asian-American women. STUDY DESIGN: This was a population-based cohort
      study of older women randomly selected from age and race strata. RESULTS: Weekly
      urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and
      urge incontinence being approximately equally common. In multivariate analysis,
      higher body mass index (greater than 25 kg/m2) was associated with both stress
      incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge
      incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians.
      Hysterectomy was a significant risk factor for stress incontinence (odds ratio
      2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly
      urinary incontinence reported ever having sought treatment. Pelvic floor
      exercises were the most common form of treatment, being used by 29% of Asian
      women with weekly incontinence. Asians were less likely then white women to
      report anal incontinence (21% versus 29%, P = .007), although this difference
      became nonsignificant after adjusting for differences in risk factors.
      CONCLUSION: Asian women share some risk factors for stress and urge urinary
      incontinence with white women. Urinary incontinence is associated with anal
      incontinence among Asian women.

PMID- 16643822
TI  - Recent use of condoms and emergency contraception by women who selected condoms
      as their contraceptive method.
AB  - OBJECTIVE: This study was undertaken to determine how consistently indigent,
      predominantly Hispanic women who had previously selected male condoms as their
      contraceptive method had used condoms and emergency contraception (EC) during the
      2 weeks before their family planning clinic visit and reasons for any nonuse.
      STUDY DESIGN: Cross-sectional survey with no personal identifiers collected.
      RESULTS: Two hundred forty-eight women were surveyed. Overall, 43.8% of sexually
      active women reported inconsistent condom use during the prior 14 days. Only 39%
      of women who had not used condoms consistently used EC at least once. The most
      common reason for nonuse of both condoms (44%) and EC (41%) was that the woman
      did not perceive that she was at risk. CONCLUSION: Inconsistent use of condoms
      and low use of EC are very frequent, even in a short-time frame. Patients may be
      reluctant to volunteer to clinicians their real contraceptive choices. Risk
      taking occurs at high rates, even among couples provided ready and free access to
      male condoms and EC.

PMID- 16643824
TI  - Variation in vaginal immune parameters and microbial hydrolytic enzymes in
      bacterial vaginosis positive pregnant women with and without Mobiluncus species.
AB  - OBJECTIVE: This study was undertaken to assess if levels of interleukin-1beta (IL
      1beta), IL-8, sialidase, prolidase and immunoglobulin A against Gardenerella
      vaginalis hemolysin (anti-Gvh IgA) in vaginal secretions differ between BV+ women
      with (M+) and without (M-) Mobiluncus spp. STUDY DESIGN: Vaginal secretions were
      obtained from 265 women at their first prenatal care visit and assessed for all
      study parameters. Gram stain evaluation using Nugent criteria was performed and
      coinfection with sexually transmitted infections determined. Differences between
      BV+/M+ and BV+/M- women were evaluated using the chi2 statistic or Mann-Whitney
      test. RESULTS: Of the 265 BV+ women, 43% (n = 113) were M+ of which 97% (n = 110)
      had Nugent scores of 9 or 10 . BV+/M+ women had elevated levels of sialidase
      (median value: 4.11 nmol vs 1.91 nmol of converted substrate; P = .003) but no
      difference in prolidase, anti-Gvh IgA, IL-1beta, IL-8, levels were found between
      the two groups. BV+/M- women had significantly higher rates of coinfection with
      Trichomonas vaginalis. CONCLUSION: BV+/M+ women have higher vaginal
      concentrations of sialidase and lower rates of T. vaginalis compared with BV+/M-
      women. Further research is needed to assess the association of this, and other,
      microbiologic profiles to risk of adverse pregnancy outcome.

PMID- 16643825
TI  - Prediction of maternal complications and adverse infant outcome at admission for
      temporizing management of early-onset severe hypertensive disorders of pregnancy.
AB  - OBJECTIVE: We explored the association between clinical parameters at admission
      and the subsequent development of major maternal complications or adverse infant
      outcome in women with hypertensive complications of pregnancy remote from term.
      STUDY DESIGN: We drew data from a randomized trial of temporizing management in
      216 patients with hemolysis, elevated liver enzymes, and low platelets syndrome;
      severe preeclampsia; eclampsia; or hypertension-related fetal growth restriction
      and gestational ages between 24 and 34 completed weeks. End points were adverse
      infant outcome (perinatal death, severe morbidity) and major maternal
      complications (major morbidity; recurrent and newly acquired hemolysis, elevated
      liver enzymes, and low platelets; eclampsia) after admission. End point
      prevalences were comparable between the treatment and control groups. The
      association with age, parity, ethnicity, body mass index, gestational age,
      estimated fetal weight, blood pressure, antihypertensive medication, pulse rate,
      hemoglobin concentration, admitting center, diagnosis at inclusion, chronic
      hypertension, and thrombophilia was explored by logistic regression analysis.
      RESULTS: Adverse infant outcome was predominantly influenced by gestational age
      (odds ratio 0.4 per week increment). Major maternal complications were correlated
      to multiparity (odds ratio 0.4) and estimated fetal weight (odds ratio 0.9 per
      100-g increment). CONCLUSION: Prediction at admission of the clinical course of
      the disease and the development of additional maternal complications was not
      feasible.

PMID- 16643826
TI  - The promise and perils of microarray analysis.
AB  - Microarray analysis has provided a novel means of identifying clues into the
      mechanisms of disease development. As a methodology, microarray analysis holds
      the promise for genome-wide screening in which 2 tissues (diseased and normal)
      are compared, and molecular pathways that defined the phenotype of the disease
      could be precisely defined. Alternatively, microarray experiments can be used to
      differentially compare pathologically similar diseased tissues to predict
      response to chemotherapy and risk of recurrence. However, the clinician should be
      aware that various sources of error can influence microarray analysis results.
      Sources of error can be minimized but not eliminated, explaining why meticulously
      conducted experiments in different laboratories or using different platforms
      result in different lists of genes. Confirmation and validation of genome-wide
      microarray results using ancillary methods remains a critical step. With proper
      confirmatory studies and cautious interpretation, microarray analysis represents
      a powerful tool for molecular discovery.

PMID- 16643827
TI  - Prenatal alcohol exposure alters GABA(A)alpha5 expression: a mechanism of alcohol
      induced learning dysfunction.
AB  - OBJECTIVE: In a model for fetal alcohol syndrome (FAS), we have previously found
      an alteration in NMDA receptors suggesting mediation, at least in part, of
      alcohol-related learning deficit. NMDA and GABA receptors interact in a
      multisynaptic circuit for the regulation of the inhibitory tone through the CNS.
      The GABA receptor subunit GABA(A)alpha5 is involved in learning and is
      developmentally regulated, as it is excitatory in the perinatal brain and
      inhibitory in the adult. We were interested to evaluate alcohol's effect on
      GABA(A)alpha5 expression to further understand alcohol-induced learning
      dysfunction. STUDY DESIGN: Timed, pregnant C57B16/J mice were treated on
      gestational day 8 with alcohol (25% alcohol, 0.03 mL/kg i.p.) or control
      (saline). Embryos and brains were harvested 10 days after treatment, and brains
      from adult offspring were collected after evaluation in the Morris Water Maze, a
      well-established test for spatial learning. Gene expression included samples from
      at least 3 litters per timepoint, and calibrator-normalized relative real-time
      polymerase chain reaction (PCR) was performed to quantify GABA(A)alpha5 with
      GAPDH standardization. Statistical analysis included analysis of variance
      (ANOVA). RESULTS: Prenatal alcohol exposure significantly decreased GABA(A)alpha5
      expression in the embryo (P < .02) and fetal brains (P < .01) 10 days after
      therapy. However, in adult brains GABA(A)alpha5 expression was increased versus
      controls (P < .01). As previously demonstrated, prenatal alcohol exposure
      resulted in deficits in adults learning the Morris Water Maze with controls
      learning faster (P < .05). CONCLUSION: Prenatal alcohol exposure alters
      developmental GABA(A)alpha5 expression. This may further explain the long-lasting
      damage of alcohol on learning skills. Both the alcohol-induced reduction in the
      GABA(A)alpha5 subunit during development and up-regulation in adult brain may be
      related to learning deficits resulting in decreased learning potential caused by
      the developmental defect and an increased inhibition of learning resulting from
      increased expression as an adult. In combination with our previous findings,
      these suggest that alcohol-induced learning impairment is likely the result of
      alterations of both NMDA and GABA expression and function.

PMID- 16643828
TI  - Unequal placental sharing and birth weight discordance in monochorionic
      diamniotic twins.
AB  - OBJECTIVE: The purpose of this study was to define the association between
      unequal placental sharing and birth weight discordance in
      monochorionic/diamniotic twin pregnancies. STUDY DESIGN: The study comprised a
      prospective cohort of monochorionic/diamniotic twin pregnancies who were
      delivered in Kaiser Permanente-Northern California, 1997-2003. Dye injection
      studies of fresh postpartum placentas were performed. Placental sharing, cord
      insertion combinations, vascular anastomoses, gestational age, and birth weights
      were recorded. Statistical comparisons of birth weight and gestational age were
      made with the Student t test. Rates of birth weight discordance were compared
      with the chi-square test. Multivariate logistic regression models analyzed the
      relationship between variables of interest. RESULTS: Mean birth weights for
      larger and smaller twins were 2400 g and 2109 g, respectively. Twenty-two percent
      of the monochorionic/diamniotic twin pairs had birth weight discordance > or =
      20%, and 8% of these pairs had twin-twin transfusion syndrome.
      Monochorionic/diamniotic twin pairs with unequal placental sharing had a 9.8
      times greater likelihood of birth weight discordance (95% CI, 5.4-17.9) as
      compared with those pairs with equal placental sharing. CONCLUSION: Unequal
      placental sharing is a significant risk factor for birth weight discordance in
      monochorionic/diamniotic twins. Antenatal diagnosis of unequal placental sharing
      would enable improved counseling in the setting of monochorionic/diamniotic
      twins.

PMID- 16643829
TI  - STAN in clinical practice--the outcome of 2 years of regular use in the city of
      Gothenburg.
AB  - OBJECTIVE: The purpose of this study was to monitor the introduction of the STAN
      methodology (Noventa Medical, Moelndal, Sweden). STUDY DESIGN: This was a
      prospective observational study covering the total population of deliveries at
      term during 2 years. Four thousand eight hundred and thirty out of 14,687 term
      pregnancies were monitored using the STAN S 21 fetal heart monitor and the
      associated clinical guidelines. Cord artery metabolic acidosis, neonatal outcome,
      and rates of operative deliveries for fetal distress were assessed. RESULTS: The
      annual rate of STAN usage increased from 28.1% to 37.7% and was associated with a
      significant reduction in metabolic acidosis rate in the total population from
      0.76% to 0.44% (P < .05). The compliance with the clinical guidelines increased
      in cases requiring intervention. The rates for moderate/severe hypoxic neonatal
      encephalopathy were consistently low, 0.55 and 0.68 per 1000 deliveries,
      respectively, and corresponding to previous findings. The rate of operative
      delivery did not change during the 2 years in the total population. CONCLUSION:
      Increasing STAN usage provided consistent improvements in fetal outcome equalling
      those noted in the Swedish randomized controlled trial (RCT) without increasing
      operative interventions for fetal distress.

PMID- 16643830
TI  - Diagnosis of lupus after stillbirth.

PMID- 16643832
TI  - Evaluation of mitochondrial membrane potential using a computerized device with a
      tetraphenylphosphonium-selective electrode.
AB  - Mitochondrial membrane potential (Deltapsi(m)) plays important roles in the
      normal function of cells and in pathobiochemical situations. The application of
      ion-selective electrodes for the measurement of Deltapsi(m) is important for
      studying normal biological reactions and pathways and mitochondrial diseases. We
      constructed and optimized a computerized device for real-time monitoring of the
      Deltapsi(m), which included modification of tetraphenylphosphonium (TPP(+))
      selective membrane that improved reproducibility of the TPP(+)-selective
      electrode. Application of MATLAB software increased the sensitivity of the
      system. We tested our improved device for membrane potential measurements of
      isolated mitochondria (in absolute scale of millivolts). In addition, we assessed
      relative changes of Deltapsi(m) (as changes in TPP(+) concentration) of digitonin
      permeabilized cells (hepatocytes, control transmitochondrial cybrids, HeLa G and
      BSC-40) after addition of substrates, inhibitors, and uncoupler of respiratory
      chain. Our system can be successfully used for studies of many aspects of the
      regulation of mitochondrial bioenergetics and as a diagnostic tool for
      mitochondrial oxidative phosphorylation disorders.

PMID- 16643833
TI  - Aluminum determination in biological fluids and dialysis concentrates via
      chelation with 8-hydroxyquinoline and solvent extraction/fluorimetry.
AB  - We describe a simple, rapid, and sensitive fluorescence method for measurement of
      aluminum (Al) in human biological fluids, in dialysis solutions, and in tap
      water, which uses 8-hydroxyquinoline for ion chelation. The fluorescence
      intensity of the toluene-extracted metal chelate (excitation wavelength, 380 nm;
      emission wavelength, 504 nm) remains unchanged for over 48 h at room temperature.
      Fluorescence intensity is a linear function of the concentration of Al in the 2
      1000 microg/L range with detection limits of 0.7-2 microg/L. A large excess of
      other ions normally found in biological fluids does not interfere in Al
      determination. The method developed was successfully used in assaying Al in serum
      and urine of reference subjects, in serum samples from patients undergoing long
      term dialysis, and in dialysis solutions. Al concentrations, measured by this
      fluorimetric procedure, were compared with those obtained by Zeeman graphite
      furnace atomic absorption spectrometry. A correlation coefficient of 0.98 was
      obtained. The proposed method could be used for routine analysis in clinical
      laboratories for accurate determination of aluminum in aqueous or biological
      fluids.

PMID- 16643834
TI  - Stimulation of polyprenyl 4-hydroxybenzoate transferase activity by sodium
      cholate and 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate.
AB  - Polyprenyl 4-hydroxybenzoate transferase (Coq2p) plays a central role in
      ubiquinone biosynthesis. Coq2p mediates the conjugation of 4-hydroxybenzoate, the
      benzoquinone ring precursor, with the completed side chain. The activity is most
      easily assayed by measuring the rate of incorporation of 4-hydroxybenzoate as
      radiolabeled substrate into polyprenyl 4-hydroxybenzoate. The in vitro assay
      requires addition of a detergent into the reaction mixture to activate enzyme
      activity, and Triton X-100 is used for this purpose in the routine assay. We have
      found that both 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate and
      sodium cholate, but not sodium deoxycholate, lysophosphatidyl choline, or
      octylglucoside, significantly stimulate the activity over that measured with
      Triton X-100. High-performance liquid chromatography analysis of lipid extracts
      revealed that the increase of specific activity resulted in a similar increase in
      reaction product, this effect is due not merely to a better lipid extraction but
      also to the actual stimulation of enzyme activity. With our improved method, we
      were able to measure Coq2p activity with much greater sensitivity in both fresh
      and frozen/thawed mitochondria and in crude homogenates obtained from cultured
      cells. Our method will simplify evaluation of Coq2p activity in scarce biological
      materials, such as cells obtained from human tissue biopsies, and thus it will
      facilitate the biochemical characterization of ubiquinone deficiencies.

PMID- 16643835
TI  - Ubiquitin-specific protease 2 as a tool for quantification of total ubiquitin
      levels in biological specimens.

PMID- 16643836
TI  - A two-step procedure for extracting genomic DNA from dried blood spots on filter
      paper for polymerase chain reaction amplification.

PMID- 16643837
TI  - Development of a high-throughput purification method and a continuous assay
      system for chlorophyllase.
AB  - In the degradation of chlorophyll, chlorophyllase catalyzes the initial
      hydrolysis of the phytol moiety from the pigment. Since chlorophyll degradation
      is a defining feature of plant senescence, compounds inhibiting chlorophyllase
      activity may delay senescence, thereby improving shelf life and appearance of
      plant products. Here we describe the development of a 96-well plate-based
      purification and assay system for measuring chlorophyllase activity. Integrated
      lysis and immobilized metal affinity chromatography plates were used for
      purifying recombinant hexahistidine-tagged Triticum aestivum (wheat)
      chlorophyllase from Escherichia coli. Chlorophyllase assays using chlorophyll as
      a substrate showed that the immobilized fusion protein displayed kinetic
      parameters similar to those of recombinant enzyme purified by affinity
      chromatography; however, the need to extract reaction products from a multiwell
      plate limits the value of this assay for high-throughput screening applications.
      Replacing chlorophyll with p-nitrophenyl-ester substrates eliminates the
      extraction step and allows for continuous measurement of chlorophyllase activity
      in a multiwell plate format. Determination of steady state kinetic constants, pH
      rate profile, the inhibitory effects of metal ions and esterase inhibitors, and
      the effect of functional group-modifying reagents validated the utility of the
      plate-based system. The combined purification and assay system provides a
      convenient and rapid method for the assessment of chlorophyllase activity.

PMID- 16643838
TI  - An assay for Fe(II)/2-oxoglutarate-dependent dioxygenases by enzyme-coupled
      detection of succinate formation.
AB  - The Fe(II)/2-oxoglutarate-dependent dioxygenases are a catalytically diverse
      family of nonheme iron enzymes that oxidize their primary substrates while
      decomposing the 2-oxoglutarate cosubstrate to form succinate and CO(2). We report
      a generic assay for these enzymes that uses succinyl-coenzyme A synthetase,
      pyruvate kinase, and lactate dehydrogenase to couple the formation of the product
      succinate to the conversion of reduced nicotinamide adenine dinucleotide to
      nicotinamide adenine dinucleotide. We demonstrate the utility of this new method
      by measuring the kinetic parameters of two bacterial Fe(II)/2-oxoglutarate
      dependent dioxygenases. Significantly, this method can be used to investigate
      both the productive turnover reactions and the nonproductive "uncoupled"
      decarboxylation reactions of this enzyme family, as demonstrated by using wild
      type and variant forms of 2-oxoglutarate-dependent taurine dioxygenase. This
      assay is amenable to miniaturization and easily adapted to a format suitable for
      high-throughput screening; thus, it will be a valuable tool to study Fe(II)/2
      oxoglutarate-dependent dioxygenases.

PMID- 16643839
TI  - [Should interval appendicectomy be performed following the resolution of an
      appendiceal abscess?].

PMID- 16643840
TI  - [Ureteric valves: a report of two cases].
AB  - Ureteric valves are a rare cause of ureteric obstruction. Fifty cases have been
      described in the literature. We report two new cases. The first is of a 12-year
      old child with left multiple ureteric valves associated to bilateral vesico
      ureteric reflux. The patient was treated by uretero-ileoplasty with unfavourable
      evolution to renal failure. The second case is that of a proximal ureteric valve
      discovered in a 30-year-old woman who had postpartum acute pyelonephritis.
      Treatment consisted in ureteric resection-anastomosis with favourable outcome.
      Based on a review of the literature, we discuss epidemiologic, etiologic,
      diagnostic and therapeutic aspects of this malformation.

PMID- 16643841
TI  - [Sequestration of the posterobasal segment of the right lower pulmonary lobe].
AB  - Pulmonary sequestration is a rare congenital malformation that receives its blood
      supply from a systemic artery. We report a case of pulmonary sequestration
      treated by ligature of the anomalous artery without pulmonary resection.
      Pulmonary sequestration must be treated surgically before the occurrence of
      severe complications.

PMID- 16643842
TI  - [Laparoscopic treatment of para-esophageal hernias].
AB  - AIM: This retrospective study aims at analyzing the functional results obtained
      in patients operated by laparoscopy for a para-esophageal hernia. PATIENTS AND
      METHODS: From 1994 to 2004, 38 patients underwent a laparoscopic procedure for a
      symptomatic para-esophageal hiatal hernia of at least 3/4 of the proximal
      stomach: 27 females and 11 males, mean age 65 years (extreme: 22-84). There was
      no case on emergency, 4 patients had have at least one episode of intrathoracic
      volvulus. The operation consisted in gastric reduction into the abdominal cavity,
      excision of the sac, suture of the crura reinforced with a mesh in 6 patients and
      the construction of a gastric wrap. A postoperative barium swallow was performed
      on POD 3 in order to confirm the anatomical result. RESULTS: Mean operating time
      was 157 minutes (75-480), no case was converted into laparotomy. Four
      postoperative complications were observed (morbidity 10.8%): one gastric
      perforation diagnosed on POD 1, 2 severe dysphagias linked to the wrap, and one
      atelectasia. There was no death in this series. Functional results were evaluated
      by the mean of a questionnaire in 33 patients who had a follow up more than 6
      months. Thirty-three questionnaires have been sent, 3 patients were lost and one
      was dead. Among the 29 patients analyzed, 14 were very satisfied, 11 were
      satisfied and 3 were deceived by the operation. Best results are obtained in
      patients with GERD, dysphagia or postprandial cardiothoracic symptoms.
      CONCLUSION: These results compared to the published data allow us to discuss
      about indications of surgery, the necessity to removal the hernia sac, and the
      advantages to reinforce the crura by the mean of a non absorbable mesh.

PMID- 16643843
TI  - The prevention of depressive symptoms in low-income, minority children: two-year
      follow-up.
AB  - We present 2-year follow-up data on the efficacy of the Penn Resiliency Program
      (PRP), a school-based depression prevention program, with low-income,
      racial/ethnic minority children. This program taught cognitive and social problem
      solving skills to 168 Latino and African American middle school children who were
      at-risk for developing depressive symptoms by virtue of their low-income status.
      We had previously reported beneficial effects of the PRP up to 6 months after the
      conclusion of the program for the Latino children, but no clear effect for the
      African American children. In this paper, we extend the analyses to 24 months
      after the conclusion of the PRP. We continue to find some beneficial effects for
      the Latino children and no differentially beneficial effect for the African
      American children. Implications of findings and future research directions are
      discussed.

PMID- 16643844
TI  - Jumping to interpretations: social anxiety disorder and the identification of
      emotional facial expressions.
AB  - A small body of research suggests that socially anxious individuals show biases
      in interpreting the facial expressions of others. The current study included a
      clinically anxious sample in a speeded emotional card-sorting task in two
      conditions (baseline and threat) to investigate several hypothesized biases in
      interpretation. Following the threat manipulation, participants with generalized
      social anxiety disorders (GSADs) sorted angry cards with greater accuracy, but
      also evidenced a greater rate of neutral cards misclassified as angry, as
      compared to nonanxious controls. The controls showed the opposite pattern,
      sorting neutral cards with greater accuracy but also misclassifying a greater
      proportion of angry cards as neutral, as compared to GSADs. These effects were
      accounted for primarily by low-intensity angry cards. Results are consistent with
      previous studies showing a negative interpretive bias, and can be applied to the
      improvement of clinical interventions.

PMID- 16643845
TI  - Differential role of p38 mitogen activated protein kinase for cellular recovery
      from attack by pore-forming S. aureus alpha-toxin or streptolysin O.
AB  - Following the observation that cells are able to recover from membrane lesions
      incurred by Staphylococcus aureus alpha-toxin and streptolysin O (SLO), we
      investigated the role of p38 in this process. p38 phosphorylation occurred in
      response to attack by both toxins, commencing within minutes after toxin
      treatment and waning after several hours. While SLO reportedly activates p38 via
      ASK1 and ROS, we show that this pathway does not play a major role for p38
      induction in alpha-toxin-treated cells. Strikingly divergent effects of p38
      blockade were noted depending on the toxin employed. In the case of alpha-toxin,
      inhibition of p38 within the time frame of its activation led to disruption of
      the recovery process and to cell death. In contrast, blockade of p38 in SLO
      permeabilized cells did not affect the capacity of the cells to replenish their
      ATP stores.

PMID- 16643846
TI  - Effects of bone marrow stromal cell injection in an experimental glaucoma model.
AB  - We investigated if bone marrow stromal cells (BMSCs) transplanted into the
      vitreous body of a glaucoma model eye could be integrated in the host retina and
      also whether they could rescue the retinal ganglion cells (RGCs) from death
      induced by the elevated intraocular pressure. Glaucoma was induced in the right
      eye of adult Wistar rats by ligating the episcleral veins. The GFP-expressing
      BMSCs (GFP-BMSCs) were injected into the vitreous body of both the control and
      the glaucomatous eyes. After transplantation, GFP-BMSCs were mostly present along
      with the inner limiting membrane and only a few cells were integrated into the
      ganglion cell layer. At 2 or 4 weeks after transplantation, GFP-BMSCs were
      observed to express various trophic factors. The BMSCs injected glaucoma model
      eyes showed less reduction in the number of RGCs compared to the glaucomatous
      eyes with PBS injection. This study suggests that BMSC transplantation may be
      worthy as a neuroprotective tool to treat glaucoma.

PMID- 16643847
TI  - Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on
      human T cells.
AB  - Co-signal receptors provide crucial activating or attenuating signals for T
      cells. The B and T lymphocyte attenuator (BTLA/CD272) is a third member of co
      inhibitory receptors, which belongs to the CD28 immunoglobulin-superfamily. Using
      monoclonal antibodies (mAbs) against human BTLA, we show that BTLA is
      constitutively expressed on most CD4+ and CD8+ T cells and its expression
      progressively decreases upon T cell activation. Polarized Th1 and Th2 cells
      contained both BTLA-positive and BTLA-negative populations, but the extended
      culture diminished BTLA expression. Cross-linking BTLA with an agonistic mAb
      inhibited T cell proliferation and the production of the cytokines IFN-gamma and
      IL-10 in response to anti-CD3 stimulation. BTLA-mediated inhibition of T cell
      activation occurred during both primary CD4+ T cell responses and secondary CD4+
      and CD8+ T cell responses, suggesting that BTLA ligation sends a constitutive
      "off" signal to T cells and thus might play an important role in the maintenance
      of T cell tolerance.

PMID- 16643848
TI  - Molecular mechanisms involved in transcriptional activation of the human Sia
      alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene
      induced by KCl in human glioblastoma cells.
AB  - In the present study, we have shown that KCl known as an inducer for
      differentiation of neuronal cells increases the human Sia-alpha2,3-Gal-beta1,4
      GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene transcription via
      phosphoinositide 3 kinase (PI-3K) in glioblastoma U-87MG cells. The induction of
      hST8Sia III by KCl is regulated at the transcriptional level in a dose- and time
      dependent manner as evidenced by reverse transcription-polymerase chain reaction
      (RT-PCR). To elucidate the mechanism underlying the regulation of hST8Sia III
      gene expression in U-87MG cells induced by KCl, we characterized the promoter
      region of the hST8Sia III gene. Functional analysis of the 5'-flanking region of
      the hST8Sia III gene by the transient expression method showed that the -1194 to 
      816 region functions as the KCl-inducible promoter in U-87MG cells. Furthermore,
      as evidenced by Western blot analysis and RT-PCR, KCl-induced expression of
      hST8Sia III gene was dependent on the PI-3K signal transduction pathway during
      the neuronal differentiation of U-87 cells, as an increase in beta-tubulin III
      known as a neuronal differentiation marker was observed. In KCl-depolarization on
      U-87 cells, the PI-3K-dependent promoter activation at the -1194 to -816 region
      up-regulated expression of hST8Sia III gene. These results suggest that the
      expression of hST8Sia III gene via the PI-3K signaling pathway is enhanced during
      KCl-induced differentiation of U-87 cells by increasing expression of beta
      tubulin III.

PMID- 16643849
TI  - Inhibition of cytochrome c oxidase subunit 4 precursor processing by the hypoxia
      mimic cobalt chloride.
AB  - Cobalt is often used as a hypoxia mimic in cell culture, because it stabilizes
      the alpha subunits of the transcription factor, HIF (hypoxia-inducible factor).
      We have previously shown that HIF stabilization due to a deficiency of the von
      Hippel Lindau protein (pVHL) in clear cell renal carcinoma (CRCC) was correlated
      to a down-regulation of oxidative phosphorylation. To better understand this
      mechanism, we have used CoCl2 in CRCC expressing stably transfected vhl. We show
      that, in addition to its effect on HIF-alpha subunits, CoCl2 prevented the normal
      processing of the precursor of cytochrome c oxidase (COX) subunit 4 and induced
      COX degradation very likely by inhibiting the mitochondrial intermediate
      peptidase (MIP) that cleaves the COX4 precursor protein. This cobalt-induced MIP
      inhibition was however not observed in other human mitochondrial precursor
      sequences as previously predicted from comparison between human and yeast
      mitochondrial precursor sequences.

PMID- 16643850
TI  - Restoration of ENaC expression by glucocorticoid receptor transfection in human
      HT-29/B6 colon cells.
AB  - The epithelial sodium channel (ENaC) controls colonic sodium absorption. So far,
      investigation of ENaC was limited by an unexplained lack of steroid-dependent
      ENaC expression in cultured intestinal cells, which we aimed to resolve. HT-29/B6
      cells constitutively expressed the alpha-ENaC subunit, while beta- and gamma-ENaC
      subunits could not be detected due to deficient basal as well as corticosteroid
      induced transcription. This was due to a lack of expression of both activating
      and inhibiting isoforms of glucocorticoid receptor (GR-alpha, -beta) and
      mineralocorticoid receptor. Stable transfection of GR-alpha restored intestine
      specific glucocorticoid upregulation of beta- and gamma-ENaC in HT-29/B6 cells,
      which was followed by intact targeting of ENaC channels to the apical cell
      membrane and dose-dependent induction of electrogenic sodium absorption. In
      conclusion, ENaC deficiency is due to a lack of steroid receptors and not the
      consequence of a crypt-like phenotype of cultured intestinal cells. By stable GR
      transfection we obtained a model, in which ENaC regulation can be studied.

PMID- 16643851
TI  - Expression of Tsga10 sperm tail protein in embryogenesis and neural development:
      from cilium to cell division.
AB  - Tsga10 has been localised in sperm tail as a fibrous sheath protein. In this
      study, we showed its expression during developmental stages of mouse embryo, in
      adult mice brain, and in some malignancies. RT-PCR and immunohistochemistry study
      show that Tsga10 expression starts in 4.5-7.5 dpc mouse embryos and continues
      throughout embryogenesis. Then we showed that the Tsga10 is expressed in adult
      brain and in the cells with neural crest origin, olfactory epithelium, and human
      germ cell tumour. It is expressed with two transcripts in sperm and whole embryos
      but just with the long transcript in brain embryo as a result of its exon 16
      splicing. Our finding of the Tsga10 perinuclear localisation and its expression
      pattern suggests that it may be involved in active cell division,
      differentiation, and migrating cells. The results of the experiments in this
      project hypothesize the presence of Tsga10 protein wherever there is a conserved
      ciliary structure.

PMID- 16643852
TI  - LoPPS: a long PCR product sequencing method for rapid characterisation of long
      amplicons.
AB  - Here, we propose an optimised protocol (LoPPS, long PCR product sequencing) which
      allows the fast, cost-attractive, and high-throughput sequencing of long PCR
      products. LoPPS constitutes an alternative to the primer-walking technology which
      is expensive and time consuming but remains the current standard procedure. It is
      based on the ultrasonic shearing, polishing, and cloning of PCR or RT-PCR
      products and is compatible with 96- or 384-well microplate systems in which
      bacterial growth, preparation of plasmid DNA, and sequencing can be automated. We
      present results obtained from 24 different RT-PCR products (2.5-4.8 kbp long)
      obtained from various RNA viruses and fully sequenced using LoPPS. The method
      proved to be robust and fast. It was successfully used on a low amount of DNA and
      allowed each target nucleotide position to be controlled twice or more, with a
      final cost which is one-third of that of primer-walking.

PMID- 16643853
TI  - Homotypic cell contact enhances insulin but not glucagon secretion.
AB  - Intra-islet interactions influence beta-cell function, and disruption of islet
      architecture results in a reduction in glucose-induced insulin secretion, whereas
      re-aggregation improves secretory responsiveness. Our studies on MIN6 cells have
      shown that by configuring beta-cells as three-dimensional islet-like structures
      there is a marked improvement in glucose-induced insulin secretion compared to
      that of their monolayer equivalents. In the present study, we have used the mouse
      glucagon-secreting alphaTC1 cell line to see whether homotypic interactions are
      important in the regulation of glucagon secretion from alpha-cells. We found no
      significant difference in the secretory responses of alphaTC1 cells maintained as
      monolayers or as cell clusters. We also found that different cell adhesion
      molecules are involved in cell interactions between alpha- and beta-cells; MIN6
      cells express ECAD, whereas alphaTC1 cells express NCAM. ECAD is necessary for
      cell cluster formation by MIN6 cells but not by alphaTC1 cells, whereas NCAM is
      not needed for the formation of cell clusters in either cell line.

PMID- 16643854
TI  - Expression of D2 dopamine receptor in the mouse brain.
AB  - The neurotransmitter, dopamine, binds to dopamine receptor (DR), and is involved
      in several functions of the brain, such as initiation and execution of movement,
      emotion, prolactin secretion, etc. Of all the five DRs, D2 dopamine receptor has
      maximal affinity for dopamine. D2 has a short isoform, D2S, and a long isoform
      D2L. D2L is longer than D2S by 29 amino acid residues. We studied the expression
      of the gene and protein of D2 receptor in the cerebral and cerebellar cortices of
      the brain of new born, developing, adult, and old male mice to find out: (i) at
      what stage of development, expression of the gene peaks and (ii) if it undergoes
      any changes as the animal ages, which may account for the neurodegenerative
      changes and symptoms of Parkinson's and other diseases seen in old age. RT-PCR
      and Western blot studies show that peak expression of D2 gene occurs in the
      cerebral and cerebellar cortices around 15-day after birth. We speculate that the
      majority of dopaminergic synapses are established and possibly become functional
      in the brain around 15-day after birth. The expression of D2 receptor is
      upregulated in the cerebral cortex in old mice. However, it is down-regulated in
      the cerebellar cortex.

PMID- 16643855
TI  - A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR
      signaling.
AB  - Toll-like receptors (TLRs) play an important role as a sensor of microbial
      pathogens in the innate immune response. TLRs transmit signals through the
      recruitment of adaptor proteins including tumor necrosis factor-associated factor
      6 (TRAF6), which mediates the activation of IkappaB kinase (IKK). TIFA (TRAF
      interacting protein with a forkhead-associated (FHA) domain) has been shown to
      bind to TRAF6 and activate IKK by promoting the oligomerization and ubiquitin
      ligase activity of TRAF6. FHA domains preferentially bind to phospho-threonine
      residues in their targets. Here, we identified a novel zinc finger protein,
      ZCCHC11, that interacts with TIFA from phosphoproteins of a macrophage cell line,
      RAW 264.7, by using affinity purification with GST-TIFA and mass spectrometric
      analysis. By a search of the EST database, we found a 200kDa full-length form
      (ZCCHC11L). ZCCHC11L was mostly located to the nucleus, but translocated into the
      cytoplasm in response to LPS and bound to TIFA. Overexpression and knockdown by
      siRNA indicated that ZCCHC11 functions as a negative regulator of TLR-mediated NF
      kappaB activation. The N-terminal region (ZCCHC11S) including C2H2-type
      [corrected] Zn-finger motif was sufficient for suppression of NF-kappaB. We
      propose that ZCCHC11 is a unique TLR signal regulator, which interacts with TIFA
      after LPS treatment and suppresses the TRAF6-dependent activation of NF-kappaB.

PMID- 16643856
TI  - Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete
      pancreatic beta-cell destruction. New evidence suggests that beta-cell
      regeneration is possible, but ongoing autoimmune damage prevents restoration of
      beta-cell mass. We tested the hypothesis that simultaneously blocking autoimmune
      cytokine damage and supplying a growth-promoting stimulus for beta-cells would
      provide a novel approach to reverse T1DM. Therefore, in this study we combined
      lisofylline to suppress autoimmunity and exendin-4 to enhance beta-cell
      proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic
      (NOD) mouse model. We found that this combined therapy effectively reversed new
      onset diabetes within a week of therapy, and even maintained euglycemia up to 145
      days after treatment withdrawal. The therapeutic effect of this regimen was
      associated with improved beta-cell metabolism and insulin secretion, while
      reducing beta-cell apoptosis. It is possible that such combined therapy could
      become a new strategy to defeat T1DM in humans.

PMID- 16643857
TI  - Over-expression in Escherichia coli and characterization of two recombinant
      isoforms of human FAD synthetase.
AB  - FAD synthetase (FADS) (EC 2.7.7.2) is a key enzyme in the metabolic pathway that
      converts riboflavin into the redox cofactor FAD. Two hypothetical human FADSs,
      which are the products of FLAD1 gene, were over-expressed in Escherichia coli and
      identified by ESI-MS/MS. Isoform 1 was over-expressed as a T7-tagged protein
      which had a molecular mass of 63kDa on SDS-PAGE. Isoform 2 was over-expressed as
      a 6-His-tagged fusion protein, carrying an extra 84 amino acids at the N-terminal
      with an apparent molecular mass of 60kDa on SDS-PAGE. It was purified near to
      homogeneity from the soluble cell fraction by one-step affinity chromatography.
      Both isoforms possessed FADS activity and had a strict requirement for MgCl(2),
      as demonstrated using both spectrophotometric and chromatographic methods. The
      purified recombinant isoform 2 showed a specific activity of 6.8+/-1.3nmol of FAD
      synthesized/min/mg protein and exhibited a K(M) value for FMN of 1.5+/-0.3microM.
      This is the first report on characterization of human FADS, and the first cloning
      and over-expression of FADS from an organism higher than yeast.

PMID- 16643858
TI  - Differential display profiling of the Nicotiana response to LPS reveals elements
      of plant basal resistance.
AB  - The identification of cDNAs, representing up-regulated genes induced by
      lipopolysaccharides from Burkholderia cepacia, was achieved by differential
      display of mRNAs isolated from tobacco cells. In addition to up-regulation of
      superoxide dismutase, involved in the production of the signalling and defense
      molecule, hydrogen peroxide; differentially expressed cDNAs, indicative of the
      operation of an innate immune recognition system and expression of basal
      resistance, were identified. These include homologs to a receptor-like protein
      kinase; a binding protein for the type III secreted effector protein, harpin; a
      virus resistance N gene; an endogenous pararetrovirus and the Pto kinase. The
      altered gene expression may be responsible for activation of surveillance
      mechanisms and enhancement of the non-self recognition capacity. The putative
      roles of these transcripts in LPS-induced responses are discussed in relation to
      emerging concepts of innate immunity.

PMID- 16643860
TI  - Relevance of astrocytic activation to reductions of astrocytic GABAA receptors.
AB  - Although astrocytes express gamma-aminobutyric acid subtype-A (GABAA) receptors
      in the mature brain, GABAA receptor expression in a cultivation state remains
      controversial. In this study, we investigated the alteration of astrocytic GABAA
      receptor expression in in vitro and in vivo studies to elucidate the relevance of
      astrocytic activation to reductions of astrocytic GABAA receptors. The GABA
      evoked Cl- current (GABAA response) in cultured astrocytes was determined by
      recording in the whole-cell mode using a conventional patch-clamp technique under
      voltage-clamp conditions. The respective amplitudes of GABAA responses on days in
      vitro 1, 3-5, 7-10, and 12-15 were 1019+/-97, 512+/-76, 84+/-21, and 22+/-9 pA,
      respectively, suggesting that the GABAA response subsequently diminished with in
      vitro aging. In immunohistochemical and biochemical analyses, the expression of
      GABAA receptor beta-subunit decreased, whereas expressions of glial fibrillary
      acidic protein (GFAP) and S100B, hallmarks of astrocytic activation, increased
      dramatically in the cultured astrocytes with in vitro aging. With the use of
      [3H]SR95531, a GABAA-specific ligand, at 24 h after transient focal ischemia,
      binding was significantly reduced in the astrocytic fractions without affecting
      the synaptosomal fractions, and decreases in the mRNA expression level of GABAA
      receptor beta-subunits were concurrently observed. Interestingly, the loss of
      GABAA response in cultured astrocytes was mitigated by co-culturing with neurons
      or treatments with monoclonal S100B antibodies. These results indicate that
      astrocytic GABAA receptors are reduced with in vitro aging and cerebral ischemia,
      presumably through the overproduction of S100B in activated astrocytes.

PMID- 16643859
TI  - Cross-talk between angiotensin II and glucagon receptor signaling mediates
      phosphorylation of mitogen-activated protein kinases ERK 1/2 in rat glomerular
      mesangial cells.
AB  - We have recently shown that the pancreatic hormone glucagon-induced
      phosphorylation of mitogen-activated protein (MAP) kinase ERK 1/2 as well as
      growth and proliferation of rat glomerular mesangial cells (MCs) via activation
      of cAMP-dependent protein kinase A (PKA)- and phospholipase C (PLC)/Ca2+-mediated
      signaling pathways. Since circulating glucagon and tissue angiotensin II (Ang II)
      levels are inappropriately elevated in type 2 diabetes, we tested the hypothesis
      that glucagon induces phosphorylation of ERK 1/2 in MCs by interacting with Ang
      II receptor signaling. Stimulation of MCs by glucagon (10 nM) induced a marked
      increase in intracellular [Ca2+]i that was abolished by [Des-His1, Glu9]-glucagon
      (1 microM), a selective glucagon receptor antagonist. Both glucagon and Ang II
      induced ERK 1/2 phosphorylation (glucagon: 214+/-14%; Ang II: 174+/-16%; p<0.001
      versus control), and these responses were inhibited by the AT1 receptor blocker
      losartan (glucagon + losartan: 77+/-14%; Ang II + losartan: 84+/-18%; p<0.01
      versus glucagon or Ang II) and the AT2 receptor blocker PD 123319 (glucagon + PD:
      78+/-7%; Ang II + PD: 87+/-7%; p<0.01 versus glucagon or Ang II). Inhibition of
      cAMP-dependent PKA with H89 (1 microM) or PLC with U73122 (1 microM) also
      markedly attenuated the phosphorylation of ERK 1/2 induced by glucagon (glucagon
      + U73122: 109+/-15%; glucagon + H89: 113+/-16%; p<0.01 versus glucagon) or Ang II
      (Ang II + U73122: 111+/-13%; Ang II + H89: 86+/-10%; p<0.01 versus Ang II).
      Wortmannin (1 microM), a selective PI 3-kinase inhibitor, also blocked glucagon-
      or Ang II-induced ERK 1/2 phosphorylation. These results suggest that AT1
      receptor-activated cAMP-dependent PKA, PLC and PI 3-kinase signaling is involved
      in glucagon-induced MAP kinase ERK 1/2 phosphorylation in MCs. The inhibitory
      effect of PD 123319 on glucagon-induced ERK 1/2 phosphorylation further suggests
      that AT2 receptors also play a similar role in this response.

PMID- 16643861
TI  - Adrenaline contributes to prenatal respiratory maturation in rat medulla-spinal
      cord preparation.
AB  - Adrenaline is a potent respiratory regulator. However, adrenergic contribution to
      the developing respiratory center has not been studied extensively. Adrenaline
      application on embryonic day 17 medulla-spinal cord block preparations abolished
      non-respiratory activity and enhanced respiratory frequency. Phentolamine
      application on neonatal blocks that produced stable neonatal respiration resulted
      in respiratory destabilization. These results suggest that central adrenergic
      modulation is involved in fetal respiratory development and maintenance of stable
      respiration.

PMID- 16643862
TI  - The effects of erythropoietin on auditory processing following neonatal hypoxic
      ischemic injury.
AB  - Neonatal hypoxia-ischemia (HI) is a common cause of brain damage and subsequent
      behavioral deficits in premature/term infants. Rapid auditory processing deficits
      have been suggested to play a role in later language impairments in this
      population. We have previously shown auditory deficits in rats with neonatal HI
      injury and now report novel effects of behavioral sparing and neuroprotection
      following treatment with a low dose of Erythropoietin using this HI injury model.

PMID- 16643863
TI  - Temporal dynamics of attentional control settings in patients with spatial
      neglect.
AB  - Patients with spatial neglect show disproportionately slow reactions to a
      contralesional stimulus presented shortly after an ipsilesional cue. We examined
      whether this attentional bias reflects purely automatic capture of attention by
      the cue or whether it is contingent on the similarity between cue and target.
      Patients with spatial neglect reacted to letters presented in the left or right
      visual field. These target letters were pre-cued by the same letter (similar cue)
      or a different letter (dissimilar cue) presented 100 or 1000 ms prior to target
      onset in the same or the opposite visual field. At the short interval, similar
      and dissimilar ipsilesional cues captured attention comparably and strongly
      slowed reactions to contralesional targets. In contrast, while similar
      ipsilesional cues still captured attention at the long interval dissimilar cues
      ceased to affect performance. In contrast, the different cueing conditions
      induced only small and insignificant differences in reaction times to
      ipsilesional targets. These findings suggest that attention of neglect patients
      is initially captured by all ipsilesional cues in a reflexive, stimulus-driven
      fashion, but that prolonged attentional capture may only be observed when cues
      share a property with the target.

PMID- 16643864
TI  - Expression of purinergic receptors in the hypothalamus of the rat is modified by
      reduced food availability.
AB  - ATP-sensitive P2 receptors are suggested to play an important role in the
      cerebral signal transduction. We examined the expression of the P2Y1 receptor and
      the possibly downstream-related neuronal nitric oxide synthase (nNOS) in the
      hypothalamus of rats food-restricted for 3 or 10 days and rats refed after a
      restriction of 10 days. The restriction caused a reduction of the body weight and
      plasma triacylglyceride, an increase of non-esterified fatty acid levels
      correlating with a decrease of leptin levels and an enhancement of plasma
      corticosterone. All changes returned to basal levels after refeeding. The
      restriction induced an enhanced intake within 30 min after food presentation and
      a reduction in the latency. Interestingly, the latter was not abolished by
      refeeding. The daily food intake induced by refeeding was enhanced at the first
      day only. The expression of hypothalamic P2Y1 receptor/nNOS mRNA and protein and
      of leptin receptor mRNA were enhanced after restricted feeding. These changes
      were abolished after 3 days of refeeding. Immunofluorescence studies indicated
      that P2Y1 receptor and nNOS immunoreactivities are present in the dorsomedial,
      ventromedial and lateral hypothalamus and in the nucleus arcuatus. P2Y1 receptor
      positive cells were partially also nNOS-positive. The P2Y1 receptor labeling was
      restricted to cell bodies of obviously non-glial cells, whereas nNOS labeling
      could be detected also at cellular processes of these cells. In the nucleus
      arcuatus, astrocytes were identified, expressing P2Y1 receptors at cell bodies
      and cellular processes. The data suggest that restricted feeding may enhance the
      sensitivity of the hypothalamus to extracellular ADP/ATP by regulation of the
      expression of P2Y1 receptors and possibly of their signal transduction pathway
      via nitric oxide production.

PMID- 16643866
TI  - Chronic restraint stress decreases the expression of glutathione S-transferase
      pi2 in the mouse hippocampus.
AB  - Chronic restraint stress in mice affects hippocampal structure and function. Mice
      were subjected to daily restraint for 3 weeks, and gene expression in hippocampus
      was compared to controls using large-scale cDNA microarrays. We found that 444
      genes were differentially expressed, and further analysis of 6 genes by real-time
      reverse transcription PCR confirmed that 3 of them were downregulated by stress.
      These 3 genes, growth factor receptor-bound protein 2 (Grb2),
      phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (Pip5k1b), and glutathione
      S-transferase, pi2 (Gstp2), were also analyzed by in situ hybridization. The
      downregulation of Gstp2 may induce an increase of oxidative damage in the
      pyramidal cells of the CA1 and CA3 regions and granular layer of the dentate
      gyrus, leading to structural and functional damage. Those regions are affected by
      stress, and our results could help understand further the mechanisms involved in
      the occurrence of stress-related disorders.

PMID- 16643865
TI  - Cells, molecules and morphogenesis: the making of the vertebrate ear.
AB  - The development and evolution of mechanosensory cells and the vertebrate ear is
      reviewed with an emphasis on delineating the cellular, molecular and
      developmental basis of these changes. Outgroup comparisons suggests that
      mechanosensory cells are ancient features of multicellular organisms. Molecular
      evidence suggests that key genes involved in mechanosensory cell function and
      development are also conserved among metazoans. The divergent morphology of
      mechanosensory cells across phyla is interpreted here as 'deep molecular
      homology' that was in parallel shaped into different forms in each lineage. The
      vertebrate mechanosensory hair cell and its associated neuron are interpreted as
      uniquely derived features of vertebrates. It is proposed that the vertebrate otic
      placode presents a unique embryonic adaptation in which the diffusely distributed
      ancestral mechanosensory cells became concentrated to generate a large
      neurosensory precursor population. Morphogenesis of the inner ear is reviewed and
      shown to depend on genes expressed in and around the hindbrain that interact with
      the otic placode to define boundaries and polarities. These patterning genes
      affect downstream genes needed to maintain proliferation and to execute ear
      morphogenesis. We propose that fibroblast growth factors (FGFs) and their
      receptors (FGFRs) are a crucial central node to translate patterning into the
      complex morphology of the vertebrate ear. Unfortunately, the FGF and FGFR genes
      have not been fully analyzed in the many mutants with morphogenetic ear defects
      described thus far. Likewise, little information exists on the ear histogenesis
      and neurogenesis in many mutants. Nevertheless, a molecular mechanism is now
      emerging for the formation of the horizontal canal, an evolutionary novelty of
      the gnathostome ear. The existing general module mediating vertical canal growth
      and morphogenesis was modified by two sets of new genes: one set responsible for
      horizontal canal morphogenesis and another set for neurosensory formation of the
      horizontal crista and associated sensory neurons. The dramatic progress in
      deciphering the molecular basis of ear morphogenesis offers grounds for optimism
      for translational research toward intervention in human morphogenetic defects of
      the ear.

PMID- 16643867
TI  - Neural networks of response shifting: influence of task speed and stimulus
      material.
AB  - Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to
      measure brain activation, while response shifting was performed. In the
      activation phase, subjects were asked to shift their attention between two
      different types of visually presented stimuli. In the baseline phase, subjects
      were required to attend to one stimulus type only. Subjects responded by pressing
      a left or right key according to the side of presentation of the target stimuli.
      In a verbal task, subjects were required to switch between letters and numbers.
      In a figural task, subjects reacted to round and square shapes. Stimuli were
      presented for 750 or 1500 ms. Response shifting revealed significantly increased
      activation compared to non-switching in the bilateral superior parietal cortex,
      right occipital cortex, left inferior frontal cortex, left and right striatum,
      and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and
      occipital cortex activation may be due to spatial analysis during response
      shifting. Subvocal rehearsal of the task instructions may have led to activation
      in the left inferior frontal cortex. Activation in the striatum was related to
      prefrontal activation and may represent the association between basal ganglia and
      prefrontal activation during executive control. However, the most important brain
      region involved in the execution of response shifting was the bilateral DLPFC.
      Higher task speed increased executive top-down attentional control and,
      therefore, significantly increased activity in the bilateral DLPFC. Brain
      activation did not differ significantly between verbal and figural stimulus
      material. This result suggests that brain activation in the present study
      illustrates the brain regions involved in the basic cognitive mechanisms of
      response shifting.

PMID- 16643868
TI  - Human brain tissue microarrays as a platform to investigate diseases of the
      nervous system.
AB  - We constructed tissue microarray (TMA) blocks containing post-mortem human brain
      tissue from subjects with clinically and neuropathologically verified Alzheimer's
      disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy,
      Lewy body disease, multisystem atrophy (MSA) as well as an age matched control.
      Fifteen donor blocks were merged into two TMA blocks containing 72, 2-mm punch
      core samples with representative brain regions generally affected in degenerative
      disorders. Hyperphosphorylated-gamma, alpha-synuclein and beta-amyloid-related
      pathologies were estimated. The diseases were easily recognized by evaluating the
      two TMA sections and the results assessing TMA sections were comparable with the
      assessment of the whole brain sections. The assessment of TMA sections revealed
      concomitant multifocal alpha-synuclein pathology in AD, mild tau-involvement in
      the case of MSA and a slight AD-type pathology in the case of CBD. These findings
      emphasize the importance of searching for a variety of pathologies in "the whole
      brain" rather than restricting the examination to a few vulnerable regions.
      Furthermore, the TMA methodology clearly reduced the number of sections needed
      for evaluating the whole brain, it increased the amount of research material
      generated and furthermore no detailed neuroanatomical knowledge was required for
      assessment of data.

PMID- 16643869
TI  - Pectin-like acidic polysaccharide from Panax ginseng with selective antiadhesive
      activity against pathogenic bacteria.
AB  - Previous studies have revealed the inhibitory effects of an acidic polysaccharide
      purified from the root of Panax ginseng against the adhesion of Helicobacter
      pylori to gastric epithelial cells and the ability of Porphyromonas gingivalis to
      agglutinate erythrocytes. In this study, this acidic polysaccharide from P.
      ginseng, PG-F2, was investigated further, in order to characterize its
      antiadhesive effects against Actinobacillus actinomycetemcomitans,
      Propionibacterium acnes, and Staphylococcus aureus. The minimum inhibitory
      concentrations (MIC) were found to be in a range of 0.25-0.5mg/mL. However,
      results showed no inhibitory effects of PG-F2 against Lactobacillus acidophilus,
      Escherichia coli, or Staphylococcus epidermidis. PG-F2 is a pectin-type
      polysaccharide with a mean MW of 1.2 x 10(4) Da, and consists primarily of
      galacturonic and glucuronic acids along with rhamnose, arabinose, and galactose
      as minor components. The complete hydrolysis of PG-F2 via chemical or
      carbohydrolase enzyme treatment resulted in the abrogation of its antiadhesive
      activity, but limited hydrolysis via treatment with pectinase (EC. 3.2.1.15)
      yielded an oligosaccharide fraction, with activity comparable to the precursor PG
      F2 (the MIC of ca. 0.01 mg/mL against H. pylori and P. gingivalis). Our results
      suggest that PG-F2 may exert a selective antiadhesive effect against pathogenic
      bacteria, while having no effects on beneficial and commensal bacteria.

PMID- 16643870
TI  - Synthesis of a library of fucopyranosyl-galactopyranosides consisting of a
      complete set of anomeric configurations and linkage positions.
AB  - A library composed of a complete set of fucopyranosyl-galactopyranosides was
      synthesized. A perbenzylated phenylthio fucopyranoside and a series of tri-O
      benzyl-galactopyranosyl fluorides having single hydroxyl groups at the 2-, 3-, 4
      , and 6-positions were used as the glycosyl donor and glycosyl acceptors,
      respectively. The chosen set of functionalities at the anomeric centers enabled
      rapid access to the oligosaccharides based on chemoselective activation. The
      first coupling reaction was achieved by the action of
      dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST). The resulting
      disaccharide fluoride was readily activated by hafnocene
      bistrifluoromethanesulfonate [Cp2Hf(OTf)2] and glycosidated with n-octanol.

PMID- 16643871
TI  - Synthesis of cancer-associated glycoantigens: stage-specific embryonic antigen 3
      (SSEA-3).
AB  - The synthesis of the tumor-associated carbohydrate antigens SSEA-3 and Gb3 in a
      semi-convergent fashion using building blocks bearing a S-thiazolinyl (STaz)
      moiety is reported. Complete stereoselective control of a difficult alpha-(1-->4)
      galactosylation and high overall yields were achieved.

PMID- 16643872
TI  - On the nitrile effect in L-rhamnopyranosylation.
AB  - It is shown that the use of 5% acetonitrile or propionitrile in dichloromethane
      functions to increase the beta-selectivity of a number of L-rhamnopyranosylation
      reactions conducted by the thioglycoside method with activation by the 1
      benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride couple. The use of
      more significant quantities of acetonitrile or propionitrile results in the
      formation of complex reaction mixtures containing little coupled product, but
      from which Ritter-type products can be isolated.

PMID- 16643873
TI  - Structural investigation of a fucoidan containing a fucose-free core from the
      brown seaweed, Hizikia fusiforme.
AB  - A fucoidan, obtained from the hot-water extract of the brown seaweed, Hizikia
      fusiforme, was separated into five fractions by DEAE Sepharose CL-6B and
      Sepharose CL-6B column chromatography. All five fractions contained predominantly
      fucose, mannose and galactose and also contained sulfate groups and uronic acid.
      The fucoidans had MWs from 25 to 950 kDa. The structure of fraction F32 was
      investigated by desulfation, carboxyl-group reduction, partial hydrolysis,
      methylation analysis and NMR spectroscopy. The results showed that the sugar
      composition of F32 was mainly fucose, galactose, mannose, xylose and glucuronic
      acid; sulfate was 21.8%, and the MW was 92.7 kDa. The core of F32 was mainly
      composed of alternating units of -->2)-alpha-D-Man(1--> and -->4)-beta-D-GlcA(1-
      >, with a minor portion of -->4)-beta-D-Gal(1--> units. The branch points were at
      C-3 of -->2)-Man-(1-->, C-2 of -->4)-Gal-(1--> and C-2 of -->6)-Gal-(1-->. About
      two-thirds of the fucose units were at the nonreducing ends, and the remainder
      were (1-->4)-, (1-->3)- and (1-->2)-linked. About two-thirds of xylose units were
      at the nonreducing ends, and the remainder were (1-->4)-linked. Most of the
      mannose units were (1-->2)-linked, and two-thirds of them had a branch at C-3.
      Galactose was mainly (1-->6)-linked. The absolute configurations of the sugar
      residues were alpha-D-Manp, alpha-L-Fucp, alpha-D-Xylp, beta-D-Galp and beta-D
      GlcpA. Sulfate groups in F32 were at C-6 of -->2,3)-Man-(1-->, C-4 and C-6 of -
      >2)-Man-(1-->, C-3 of -->6)-Gal-(1-->, C-2, C-3 or C-4 of fucose, while some
      fucose had two sulfate groups. There were no sulfate groups in either the GlcA or
      xylose residues.

PMID- 16643874
TI  - Total synthesis of two isoflavone C-glycosides: genistein and orobol 8-C-beta-D
      glucopyranosides.
AB  - Genistein and orobol 8-C-beta-D-glucopyranosides (1 and 3) were firstly
      synthesized in overall yields of 39% and 41% from 2,4-di-O
      benzylphloroacetophenone (4), as follows: (1) the formation of the chalcone (6,
      7) by aldol condensation of the benzyl-protected C-glycosylphloroacetophenone
      (5), a key intermediate of the total synthesis of 1 and 3 and synthesized by a C
      glycosylation method involving the O-->C glycoside rearrangement of 4 in 96%
      yield; (2) the formation of isoflavones (10, 11 and 12, 13) by the formation of
      acetals by oxidative rearrangement of the protected chalcones (8 and 9) using
      Tl(NO3)3, followed by acid-catalyzed cyclization; (3) a final debenzylation by
      hydrogenolysis.

PMID- 16643875
TI  - Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in
      monocyte chemoattractant protein-1 (MCP-1)-induced cardiomyopathy.
AB  - OBJECTIVE: Infiltrating inflammatory cells within the myocardium have been shown
      to be apoptotic, but the significance of apoptotic inflammatory cells to the
      development of cardiomyopathy remains undefined. Transgenic mice with cardiac
      specific expression of MCP-1 exhibit extensive apoptosis of infiltrating
      mononuclear cells and develop heart failure. Here, we tested the hypothesis that
      in vivo selective inhibition of apoptosis of infiltrating mononuclear cells would
      preserve cardiac structure and function and improve survival in this murine
      model. METHODS: Mice with cardiac-specific expression of MCP-1 and monocyte
      specific expression of Bcl-2 were generated by cross-breeding MCP-1 transgenic
      mice with hMRP8-Bcl-2 mice that over-express Bcl-2 in the monocytes. Structural
      and functional parameters and the inflammatory response of the heart were
      evaluated and compared between the wild-type and transgenic mice. RESULTS:
      Expression of Bcl-2 in monocytes results in superior preservation of myocardial
      structure, cardiac function and a significant prolongation of survival of MCP-1
      transgenic mice. The beneficial effects of monocyte-specific Bcl-2 expression are
      associated with inhibition of apoptosis of infiltrating mononuclear cells,
      normalization of circulating C-reactive protein levels, attenuation of cellular
      infiltrates, macrophage activation and production of proinflammatory cytokines,
      tumor necrosis factor (TNF-alpha), interleukin (IL)-1 beta and IL-6 in the
      hearts. CONCLUSIONS: These results demonstrate that apoptosis of infiltrating
      mononuclear cells plays a detrimental role in the development of heart failure in
      this murine model, suggesting that modulation of apoptosis of infiltrating
      mononuclear cells may be of clinical benefit in heart failure.

PMID- 16643876
TI  - Competitive binding of pentraxins and IgM to newly exposed epitopes on late
      apoptotic cells.
AB  - A random distribution of phospholipids among the inner and outer leaflet of the
      cell membrane occurs during apoptosis and is known as membrane flip-flop. Flip
      flopped cells have binding sites for various plasma proteins, such as IgM and the
      pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP). In this
      study, we investigated whether pentraxins and IgM antibodies recognize the same
      binding sites on apoptotic cells, and whether phospholipids constitute these
      binding sites. Except for SAP which also bound to early apoptotic cells,
      pentraxins and IgM preferentially bound to late apoptotic cells. Competition
      experiments with different phosphatemonoesters revealed that CRP and SAP as well
      as part of the IgM bound to the phospholipids head groups, SAP mainly to
      phosphorylethanolamine, CRP to phosphorylcholine and phosphorylethanolamine and
      to a lesser extent to phosphorylserine, and IgM to phosphorylcholine and
      phosphorylserine. These results were confirmed in experiments in which proteins
      were adsorbed from plasma with artificial phospholipids particles. IgM and the
      pentraxins variably competed for the same binding sites on late apoptotic cells,
      SAP having the highest and CRP the lowest apparent affinity. We conclude that
      CRP, SAP, and part of the IgM bind to the phospholipid head groups exposed on
      apoptotic cells. This shared specificity as well as their shared capability to
      activate complement, suggest that IgM and the pentraxins CRP and SAP exert
      similar functions in the removal of apoptotic cells.

PMID- 16643877
TI  - Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in
      rats.
AB  - Antioxidants are one of the key players in tumorigenesis, several natural and
      synthetic antioxidants were shown to have anticancer effects. In the present
      investigation the efficacy of silymarin on the antioxidant status of N
      nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in Wistar albino male
      rats were assessed. The animals were divided into five groups. The animals in the
      groups 1 and 3 were normal control and silymarin control, respectively. Groups 2,
      4 and 5 were administered with 0.01% NDEA in drinking water for 15 weeks to
      induce hepatocellular carcinoma (HCC). Starting 1 week prior to NDEA
      administration group 4 animals were treated with silymarin in diet for 16 weeks,
      10 weeks after NDEA administration group 5 animals were treated with silymarin
      and continued till the end of the experiment period (16 weeks). After the
      experimental period the body weight, relative liver weight, number of nodules,
      size of nodules, the levels of lipid peroxidation, glutathione (GSH), and the
      activities of antioxidant enzymes were assessed in both haemolysate and liver
      tissue. In group 2 hepatocellular carcinoma induced animals there was an increase
      in the number of nodules, relative liver weight. The levels of lipid peroxides
      were elevated with subsequent decrease in the body weight, (glutathione) GSH,
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD). In
      contrast, silymarin + NDEA treated groups 4 and 5 animals showed a significant
      decrease in the number of nodules with concomitant decrease in the lipid
      peroxidation status. The levels of GSH and the activities of antioxidant enzymes
      in both haemolysate and liver were improved when compared with hepatocellular
      carcinoma induced group 2 animals. The electron microscopy studies were also
      carried out which supports the chemopreventive action of the silymarin against
      NDEA administration during liver cancer progression. These findings suggest that
      silymarin suppresses NDEA induced hepatocarcinogenesis by modulating the
      antioxidant defense status of the animals.

PMID- 16643878
TI  - Normal mode analysis of gamma form of oleic acid.
AB  - Oleic acid is one of the major components of a variety of oils and its spectra
      are very complex due to the presence of a large number of conformational states
      (alpha, beta, gamma). In the present communication, an attempt has been made to
      unravel the complex spectra by calculating the normal modes and examining the
      spectral features such as line position, line width, band intensity, group
      frequency concept and spectral relationship between the finite and infinite
      systems.

PMID- 16643879
TI  - Urinary pseudouridine in patients with lymphoma: comparison with other clinical
      parameters.
AB  - BACKGROUND: Some patients with malignant lymphoma do not manifest superficial
      lymphadenopathy. In such cases, clinical parameters that indicate the number of
      tumor cells are important for the assessment of tumor growth and choice of proper
      treatment. We evaluated urinary pseudouridine (U-PU) as an indicator of the
      growth of malignant lymphoma by comparing its levels with serum concentrations of
      other clinical parameters in patients with various lymphomas at various stages.
      METHODS: Urine was obtained from 67 patients with lymphoma. U-PU was assayed by
      recombinant Fab-based inhibition ELISA. Serum soluble IL2 receptor (sIL2R), serum
      deoxythymidine kinase (dTK), serum beta-2 microglobulin (beta2MG) and serum
      lactate dehydrogenase (LDH) were also assayed. RESULTS: U-PU concentrations
      showed good correlations with serum concentrations of beta2MG, LDH, sIL2R and
      dTK. The level of U-PU was higher in stage IV than in stages I (P=0.023), II
      (P=0.006) and III (P=0.036). CONCLUSION: U-PU concentration correlates with the
      clinical stage of lymphoma and is a useful tool to assess the growth of lymphoma.

PMID- 16643880
TI  - WITHDRAWN: Clinical Chemistry: 50 years of stimulating changes and more to come.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16643881
TI  - The analysis of densitometry image of bone tissue based on computer simulation of
      X-ray radiation propagation through plate model.
AB  - In this work, we have presented an attempt at the computer modelling of the
      attenuation effect of X-ray radiation which occurs in the densitometry test. The
      purpose of the modelling is to examine the extent to which the parameters of the
      plate model of bone tissue affect bone mineral density (BMD) parameter. In the
      modelling the fundamental functions realised by a densitometry device have been
      taken into consideration. Certain necessary assumptions simplifying the
      computation of the complex physical processes that occur during the transition of
      X-ray radiation through an object have been made. In order to compute the image
      produced by interaction of radiation the attenuation law is applied. The
      modelling of an object consists in defining its dimensions and its material
      characteristics. In the presented simulation the material characteristics of the
      object are limited to its attenuation coefficient. A different value of the
      coefficient can be defined for each voxel. The result image is produced by the
      calculation of partial attenuation in the individual voxels. The levels of grey
      in the image represent the value of the computed radiation intensity which is
      recorded in the "detector" after transition through the object. The simulation
      has been performed for the plate model representing trabecular bone tissue with
      0.1mm porosity compartments. The results of the simulation of the plate model are
      presented. It can be observed that for certain modelled porosity compartments the
      size, structure and spatial arrangement are not properly recorded in the two
      dimensional "detector". The recorded simulation results may be found useful for
      explaining difference that has been noticed between the BMD obtained from the
      densitometry test and the bone susceptibility to fracture.

PMID- 16643882
TI  - Notch pathway repression by vestigial is required to promote indirect flight
      muscle differentiation in Drosophila melanogaster.
AB  - Drosophila dorsal longitudinal muscles develop during metamorphosis by fusion of
      myoblasts with larval templates. It has been shown that both vestigial and Notch
      are crucial for correct formation of these muscles. We investigated the
      relationship between vestigial and the Notch pathway during this process. Using
      Enhancer of Split Region Transcript m6 gene expression as a reporter of Notch
      pathway activity, we were able to demonstrate that this pathway is only active in
      myoblasts. Moreover, close examination of the cellular location of several of the
      main actors of the N pathway (Notch, Delta, neuralized, Serrate, Mind bomb1 and
      fringe) during dorsal longitudinal muscle development enabled us to find that
      Notch receptor can play multiple roles in adult myogenesis. We report that the
      locations of the two Notch ligands (Delta and Serrate) are different.
      Interestingly, we found that fringe, which encodes a glycosyltransferase that
      modifies the affinity of the Notch receptor for its ligands, is expressed in
      muscle fibers and in a subset of myoblasts. In addition, we demonstrate that
      fringe expression is essential for Notch pathway inhibition and muscle
      differentiation. Lastly, we report that, in vestigial mutants, fringe expression
      is lost, and when fringe is overexpressed, a significant rescue of indirect
      flight muscle degeneration is obtained. Altogether, our data show that a
      vestigial-differentiating function is achieved through the inhibition of the
      Notch pathway.

PMID- 16643883
TI  - Laminin isoforms and lung development: all isoforms are not equal.
AB  - Laminins are a major component of basement membranes. Each laminin molecule is a
      heterotrimeric glycoprotein composed of one alpha, one beta, and one gamma chain.
      Fifteen laminin isoforms exist, assembled from various combinations of 5alpha,
      3beta, and 3gamma chains. The embryonic lung has abundant laminin isoforms.
      Increasing evidence suggests that different laminin isoforms have unique
      functions in lung development. Studies of embryonic lung explants and organotypic
      co-cultures show that laminin alpha1 and laminin 111 are important for epithelial
      branching morphogenesis and that laminin alpha2 and laminin 211 have a role in
      smooth muscle cell differentiation. In vivo studies of laminin alpha5-deficient
      mice indicate that this laminin chain, found in laminins 511 and 521, is
      essential for normal lobar septation in early lung development and normal
      alveolization and distal epithelial cell differentiation and maturation in late
      lung development. However, not all of the laminin chains present in the
      developing lung appear to be necessary for normal lung development since laminin
      alpha4 null mice do not have obvious lung abnormalities and laminin gamma2 null
      mice have only minimal changes in lung development. The mechanisms responsible
      for the lung phenotypes in mice with laminin mutations are unknown, but it is
      clear that multiple laminin isoforms are crucial for lung development and that
      different laminin isoforms exhibit specific, non-overlapping functions.

PMID- 16643884
TI  - Activin A is an endogenous inhibitor of ureteric bud outgrowth from the Wolffian
      duct.
AB  - Development of metanephric kidney begins with ureteric bud outgrowth from the
      Wolffian duct (WD). GDNF is believed to be a crucial positive signal in the
      budding process, but the negative regulation of this process remains unclear.
      Here, we examined the role of activin A, a member of TGF-beta family, in bud
      formation using an in vitro WD culture system. When cultured with the surrounding
      mesonephros, WDs formed many ectopic buds in response to GDNF. While the activin
      signaling pathway is normally active along the non-budding WD (as measured by
      expression of activin A and phospho-Smad2/3), activin A was absent and phospho
      Smad2/3 was undetectable in the ectopic buds induced by GDNF. To examine the role
      of activin A in bud formation, we attempted to inactivate activin action.
      Interestingly, the addition of neutralizing anti-activin A antibody potentiated
      GDNF action. To further clarify the role of activin A, we also tested the effect
      of activin blockade on the WD cultured in the absence of mesonephros. WDs without
      mesonephros did not form ectopic buds even in the presence of GDNF. In contrast,
      blockade of activin action with a variety of agents acting through different
      mechanisms (natural antagonist, neutralizing antibodies, siRNA) enabled GDNF to
      induce ectopic buds. Inhibition of GDNF-induced bud formation by activin A was
      accompanied by inhibition of cell proliferation, reduced expression of Pax-2, and
      decreased phosphorylation of PI3-kinase and MAP kinase in the WD. Our data
      suggest that activin A is an endogenous inhibitor of bud formation and that
      cancellation of activin A autocrine action may be critical for the initiation of
      this process.

PMID- 16643885
TI  - Yolk proteolysis and aquaporin-1o play essential roles to regulate fish oocyte
      hydration during meiosis resumption.
AB  - In marine fish, meiosis resumption is associated with a remarkable hydration of
      the oocyte, which contributes to the survival and dispersal of eggs and early
      embryos in the ocean. The accumulation of ions and the increase in free amino
      acids generated from the cleavage of yolk proteins (YPs) provide the osmotic
      mechanism for water influx into the oocyte, in which is involved the recently
      identified, fish specific aquaporin-1o (AQP1o). However, the timing when these
      processes occur during oocyte maturation, and the regulatory pathways involved,
      remain unknown. Here, we show that gilthead sea bream AQP1o (SaAQP1o) is
      synthesized at early vitellogenesis and transported towards the oocyte cortex
      throughout oocyte growth. During oocyte maturation, shortly after germinal
      vesicle breakdown and before complete hydrolysis of YPs and maximum K(+)
      accumulation is reached, SaAQP1o is further translocated into the oocyte plasma
      membrane. Inhibitors of yolk proteolysis and SaAQP1o water permeability reduce
      sea bream oocyte hydration that normally accompanies meiotic maturation in vitro
      by 80% and 20%, respectively. Thus, yolk hydrolysis appears to play a major role
      to create the osmotic driving force, while SaAQP1o possibly facilitates water
      influx into the oocyte. These results provide further evidence for the role of
      AQP1o mediating water uptake into fish oocytes, and support a novel model of fish
      oocyte hydration, whereby the accumulation of osmotic effectors and AQP1o
      intracellular trafficking are two highly regulated mechanisms.

PMID- 16643886
TI  - Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon,
      and bone development.
AB  - The mature heart valves are dynamic structures composed of highly organized cell
      lineages and extracellular matrices. The discrete architecture of connective
      tissue within valve leaflets and supporting structures allows the valve to
      withstand life-long functional demands and changes in hemodynamic forces and
      load. The dysregulation of ECM organization is a common feature of heart valve
      disease and can often be linked to genetic defects in matrix protein structure or
      developmental regulation. Recent studies have identified specific regulatory
      pathways that are active in the developing valve structures and also control
      cartilage, tendon, and bone development. This review will focus on the regulatory
      hierarchies that control normal and abnormal heart valve development in parallel
      with other connective tissue cell types.

PMID- 16643887
TI  - Dpp and Gbb exhibit different effective ranges in the establishment of the BMP
      activity gradient critical for Drosophila wing patterning.
AB  - Morphogen gradients ensure the specification of different cell fates by dividing
      initially unpatterned cellular fields into distinct domains of gene expression.
      It is becoming clear that such gradients are not always simple concentration
      gradients of a single morphogen; however, the underlying mechanism of generating
      an activity gradient is poorly understood. Our data indicate that the relative
      contributions of two BMP ligands, Gbb and Dpp, to patterning the wing imaginal
      disc along its A/P axis, change as a function of distance from the ligand source.
      Gbb acts over a long distance to establish BMP target gene boundaries and a
      variety of cell fates throughout the wing disc, while Dpp functions at a shorter
      range. On its own, Dpp is not sufficient to mediate the low-threshold responses
      at the end points of the activity gradient, a function that Gbb fulfills. Given
      that both ligands signal through the Tkv type I receptor to activate the same
      downstream effector, Mad, the difference in their effective ranges must reflect
      an inherent difference in the ligands themselves, influencing how they interact
      with other molecules. The existence of related ligands with different functional
      ranges may represent a conserved mechanism used in different species to generate
      robust long range activity gradients.

PMID- 16643888
TI  - The in vivo effect of adrenomedullin on rat dural and pial arteries.
AB  - Adrenomedullin is related to the calcitonin gene-related peptide (CGRP) family
      and is present in cerebral blood vessels. It may be involved in migraine
      mechanisms. We measured the change in dural and pial artery diameter, mean
      arterial blood pressure and local cerebral blood flow flux (LCBF(Flux)) after
      intravenous (i.v.) infusion of adrenomedullin. The study was performed in the
      presence or absence of the CGRP1 (calcitonin-receptor-like-receptor
      (CALCRL)/receptor activity-modifying protein-1 (RAMP1)) receptor antagonists
      BIBN4096BS, CGRP-(8-37) and the adrenomedullin receptor antagonist adrenomedullin
      (22-52). I.v. infusion of 15 mug kg(-1) adrenomedullin (n=8) induced dilatation
      of dural (32+/-7.5%) and pial (18+/-5.5%) arteries, a reduction in mean arterial
      blood pressure (19+/-3%) and an increase in LCBF(Flux) (16+/-8.4%). The duration
      of the responses was 25 min for the dural artery, while the response of the pial
      artery lasted for 15 min. The CGRP1-receptor antagonists BIBN4096BS and CGRP-(8
      37) and the adrenomedullin receptor antagonist adrenomedullin-(22-52)
      significantly inhibited the effect of adrenomedullin (n=7, P<0.05 for both
      arteries) on dural and pial artery diameter and mean arterial blood pressure. No
      significant inhibition of LCBF(Flux) was found. The antagonist alone had no
      effect on mean arterial blood pressure or LCBF(Flux). In conclusion, we suggest
      that adrenomedullin in the rat cranial circulation dilates dural and pial
      arteries, reduces mean arterial blood pressure and increases LCBF(Flux), probably
      via a CGRP1-receptor.

PMID- 16643889
TI  - Effects of adenosine A(3) receptor agonist on bone marrow granulocytic system in
      5-fluorouracil-treated mice.
AB  - The purpose of the experiments reported was to investigate effects of N(6)-(3
      iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), a selective adenosine A(3)
      receptor agonist, on the granulocytic system in femoral marrow of mice depleted
      by the cytotoxic drug 5-fluorouracil. In the phase of the highest cell depletion
      IB-MECA was injected i.p. at single doses of 200 nmol/kg given either once or
      twice daily in 2- and 4-day regimens starting on day 1 after 5-fluorouracil
      administration; the effects were evaluated on days 3 and 5, respectively. The
      general effect of IB-MECA in all these experiments was an enhancement of the
      counts of morphologically recognizable proliferative granulocytic cells,
      interpreted as evidence of the differentiation of committed progenitor cells. A
      more expressive effect was observed after IB-MECA injected twice daily. It was
      found that the induction of the strong differentiation pressures by IB-MECA given
      twice daily shortly after 5-fluorouracil treatment can be counterproductive due
      to the preponderance of differentiaton processes over the proliferation control.
      In additional experiments, it has been shown that the use of the 2-day
      administration of IB-MECA given twice daily in the recovery phase, i.e., on days
      5 and 6 after 5-fluorouracil administration, does not induce stimulatory effects.
      Thus, the dosing and timing of IB-MECA treatment determines its effectivity in
      stimulating granulopoiesis under conditions of myelosuppression.

PMID- 16643890
TI  - Raloxifene promotes adipocyte differentiation of 3T3-L1 cells.
AB  - To explore the possibility that raloxifene might influence an adipocyte
      differentiation and lipogenesis, we studied the effects of raloxifene on the
      expression of adiponectin and other peroxisome proliferator-activated receptor
      gamma targeting genes using the 3T3-L1 adipocytes. With standard adipogenic
      inducers, we added raloxifene at various doses for the adipocyte differentiation.
      Higher doses of raloxifene facilitated lipid accumulation of the 3T3-L1 cells. We
      next examined the differentiating and differentiated adipocytes and found that
      raloxifene augmented mRNA levels of adiponectin, adipocyte-specific fatty acid
      binding protein, and lipoprotein lipase dose-dependently in both. These effects
      were opposite those of 17beta-estradiol treatment. These findings suggest that
      raloxifene promotes adipocyte differentiation, providing a novel insight into the
      treatment of postmenopausal metabolic syndrome with hypoadiponectinemia.

PMID- 16643891
TI  - Antibody-directed targeting of angiostatin's receptor annexin II inhibits Lewis
      Lung Carcinoma tumor growth via blocking of plasminogen activation: possible
      biochemical mechanism of angiostatin's action.
AB  - Angiostatin, the N-terminal four kringles (K1-4) of parent molecule plasminogen,
      is reported to block Lewis Lung Carcinoma (LLC) tumor growth and metastasis.
      However, angiostatin's mechanism of action is unclear. We earlier reported that
      angiostatin binds to cell surface annexin II through the lysine-binding domain
      (kringles 1-4) [Tuszynski, G.P., Sharma, M., Rothman, V.L., Sharma, M.C., 2002.
      Angiostatin binds to tyrosine kinase substrate annexin II through the lysine
      binding domain in endothelial cells. Microvasc. Res. 64:448-462.]). We now show
      that annexin II on the cell surface of LLC cells regulates conversion of
      plasminogen to plasmin. Activation of plasminogen to plasmin is time-dependent,
      with the linear activation lasting up to 120 min. Monoclonal antibodies to
      annexin II reduced plasminogen activation by 92.6%, suggesting a specific role of
      annexin II in plasmin generation. Angiostatin also reduced plasmin generation by
      81.6%, suggesting that angiostatin may be competing with plasminogen through
      lysine-binding domain. epsilon-Aminocaproic acid, a lysine analogue, effectively
      blocked plasminogen activation indicating that, indeed, the lysine-binding site
      of the kringles domain is required for activation. These data suggest that
      annexin II may be a receptor target for angiostatin's action. Therefore, we
      tested the effect of high affinity monoclonal antibody to annexin II in mouse
      model of LLC. A single dose of antibody treatment inhibited LLC tumor growth
      almost 70% with concomitant inhibition of circulating plasmin generation and its
      proteolytic activity. Taken together, it is possible that inhibition of LLC tumor
      growth and metastasis reported by angiostatin therapy may be due to blocking of
      annexin-II-dependent plasmin generation. Plasmin is known to influence
      angiogenic, invasive and metastatic capability of tumors.

PMID- 16643892
TI  - Angiogenesis-associated protein annexin II in breast cancer: selective expression
      in invasive breast cancer and contribution to tumor invasion and progression.
AB  - Many advanced human tumors including breast cancer overproduce plasmin that is
      known to promote angiogenesis and metastasis. The mechanism of this effect is
      poorly understood. Here we report that annexin II, an endothelial co-receptor for
      tPA (tissue-type plasminogen activator) and plasminogen, was undetectable in
      normal and hyperplastic ductal epithelial cells and ductal complexes. By
      contrast, it was consistently expressed in invasive breast cancer and ductal
      carcinoma in situ (DCIS) indicating its involvement in breast cancer. Using the
      well established invasive/metastatic MDA-MB231 cell line and the
      noninvasive/nonmetastatic MCF-7 human breast cancer cell line, we investigated
      the mechanism by which annexin II regulates breast cancer progression and
      metastasis. Western and Northern blot analyses demonstrate selective expression
      of annexin II in MDA-MB231 cells but not in poorly invasive MCF-7 cells
      suggesting its participation in invasive breast cancer. Since annexin II is a
      receptor for plasminogen, we tested whether MDA-MB231 cells are capable of
      producing plasmin in vitro. MDA-MB231 cell membranes induced plasmin generation
      in a time-dependent manner while those from MCF-7 cells failed to convert
      plasminogen to plasmin. The generated plasmin is capable of degrading ECM
      consequently facilitating cell invasion and migration, biological functions
      required for angiogenesis and metastasis. Plasmin generation and its dependent
      invasion and migration can be blocked by a monoclonal antibody to annexin II or
      angiostatin, potent inhibitors of angiogenesis, breast cancer, and metastasis.
      Our findings indicate that annexin II-dependent localized plasmin generation by
      human breast cancer cells could contribute to angiogenesis and metastasis. These
      results suggest that annexin II may be an attractive target for new anti
      angiogenic and anti-breast cancer therapies.

PMID- 16643893
TI  - The activated form of gelatinase B/matrix metalloproteinase-9 is associated with
      diabetic vitreous hemorrhage.
AB  - We aimed to investigate the presence and activation status of matrix
      metalloproteinase (MMP)-2 and MMP-9 in vitreous samples from proliferative
      diabetic retinopathy (PDR) patients. Paired vitreous and serum samples were
      obtained from patients undergoing vitrectomy for the treatment of rhegmatogenous
      retinal detachment (RD) (65 patients) and PDR (67 patients). PDR patients were
      diagnosed for the presence of hemorrhage and/or patent new vessels. Quantitative
      assays were performed for vitreous protein content, MMP-2, MMP-9, tissue
      inhibitor of metalloproteinases-1 (TIMP-1) and hemoglobin. Qualitative evaluation
      of the MMP-2 and MMP-9 activation status was performed by zymography. Vitreous
      samples contained proMMP-2 but levels were unselectively related to total protein
      content. ProMMP-9 and activated MMP-9 levels were significantly increased in PDR
      patients (p<0.001 for both comparisons). In addition, TIMP-1 levels were
      significantly increased in PDR patients (p=0.004) and functionally inhibited
      activation of MMP-9 in vitreous samples. None of the parameters significantly
      differed between PDR patients with patent new vessels and those with inactive
      disease. However, activated MMP-9 levels in vitreous samples of PDR patients with
      hemorrhage (75.7+/-106.3 scanning units per 2 microl) were significantly higher
      than those in PDR patients without hemorrhage (7.1+/-16.2 scanning units per 2
      microl) (p<0.001) and strongly correlated with hemoglobin levels (r=0.7525;
      p<0.001). Activated MMP-9 was not detected in paired serum samples. We conclude
      that activated MMP-9 might be involved in hemorrhagic transformation in patients
      with PDR.

PMID- 16643894
TI  - Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber
      congenital amaurosis.
AB  - TUB is the first identified member of the TULP family of four proteins with
      unknown function. A spontaneous mutation in murine tub causes retinal
      degeneration, obesity, and deafness. Mutations in another member of the TULP
      family, TULP1, are a cause of autosomal recessive retinitis pigmentosa (RP).
      These findings prompted us to investigate TUB as a candidate gene for RP and
      Leber congenital amaurosis (LCA). A mutation screen of the entire coding region
      of the TUB gene in 159 unrelated patients with autosomal recessive RP, 114
      unrelated patients with simplex RP, and 21 unrelated patients with LCA uncovered
      18 sequence variations. Of these, seven were missense mutations, six were
      isocoding changes, and five were intronic polymorphisms. All seven missense
      mutations were identified as heterozygous changes and no defect could be found in
      the other allele. None of the isocoding variants or intronic polymorphisms are
      predicted to create or destroy splice donor or acceptor sites based on splice
      site prediction software. Although variant alleles of the TUB gene were found,
      none could be definitively associated with a specific retinal disease.

PMID- 16643895
TI  - Aberrant retinal tight junction and adherens junction protein expression in an
      animal model of autosomal dominant Retinitis pigmentosa: the Rho(-/-) mouse.
AB  - Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited diseases
      that are characterised by primary degeneration of rod photoreceptors and
      secondary degeneration of cone photoreceptors in the retina. Additional
      pathological changes include vascular changes and invasion of the inner retina by
      retinal pigment epithelial (RPE) cells. RP represents a major cause of
      progressive retinal disease worldwide. Using a mouse model of autosomal dominant
      Retinitis pigmentosa (adRP) with retinopathy induced by targeted disruption of
      the rhodopsin gene Rho(-/-), we have analysed the levels of expression of a range
      of tight and adherens junction associated proteins, in order to further elucidate
      the pathogenic mechanisms occurring at an early stage of this condition. Using
      western blot analysis and indirect immunostaining of retinal cryosections from 6
      week-old mice from a C-129 background we have determined changes, if any, in the
      levels of expression and localisation of a series of tight and adherens junction
      associated proteins, including Zonula Occludens-1 (ZO-1), occludin, N-Cadherin,
      p120-Catenin, alpha-Catenin, gamma-Catenin, beta-Catenin, and E-Cadherin. We have
      found an up-regulation of the tight junction and adherens junction associated
      protein Zonula Occludens-1 (ZO-1) in the neural retina of 6-week-old Rho(-/-)
      knockout mice compared with 6-week-old Wild-Type (WT) mice. Following
      immunohistochemistry, however, it appears, that ZO-1, beta-Catenin and p120
      Catenin expression at the Outer Limiting Membrane (OLM) of the Rho(-/-) retina is
      compromised, in part, compared to WT animals of the same age. We hypothesise that
      these retinal changes following photoreceptor cell death may contribute to the
      pathogenesis of adRP. Our findings of changes in the levels of expression of ZO-1
      and associated adherens junction proteins beta-Catenin and p120-Catenin at the
      OLM in 6-week-old Rho(-/-) mice provide evidence for tight junction and adherens
      junction associated protein modifications in an animal model of autosomal
      dominant RP (adRP).

PMID- 16643896
TI  - Temporal changes in the tear menisci following a blink.
AB  - This study investigated tear meniscus formation after a blink. Multiple images of
      the inferior and superior menisci, viewed en-face, were sequentially captured
      using a video-slitlamp that permitted the measurement of tear meniscus height
      (TMH). In a similar manner, tangentially viewed images were obtained of the
      inferior meniscus so changes in cross-sectional radius of curvature (TMR) with
      time could be determined. Additionally, the relationship between inferior TMH and
      tear volume was quantified by the successive instillation of small aliquots of
      fluid. In this latter experiment the inflow and outflow of tears were controlled
      by anaesthetizing the ocular surface and inner nose, and use of punctal plugs.
      The TMH of both menisci rose after a blink (p<0.01) by a similar amount (p=0.59).
      This suggests that capillarity is dominant over gravity in tear drainage,
      however, it may simply reflect that these influences are small compared to the
      large flow resistances that occur in thin films, hydraulic connectivity between
      the two menisci, or differences in their anterior-posterior width leading to
      unequal volume-height relationships. TMR increased with time after a blink
      (p<0.0001); immediately on eye opening the curvature of the inferior meniscus was
      approximately circular but this soon became eccentric, with the radius of its
      upper half exceeding that of its lower half. The growth rate of the two menisci
      slowed with time and this, based on theoretical considerations, is predicted to
      have occurred primarily because localized thinning of the tear film adjacent to
      the menisci markedly raised flow resistance. Inferior TMH increased linearly with
      the cumulative volume of instilled fluid (r2=0.98), supporting its use in the
      diagnosis and classification of tear anomalies, although the gradient of this
      relationship varied between subjects.

PMID- 16643897
TI  - Exogenous leukemia inhibitory factor (LIF) attenuates retinal vascularization
      reducing cell proliferation not apoptosis.
AB  - To study the effect of leukemia inhibitory factor (LIF) on rat retinal vascular
      development, Sprague-Dawley rats at postnatal age 3 days (p3) were given
      intraperitoneal (IP) LIF and analysis performed at p6 (p3/6). p7 rats were given
      intravitreous (IV) LIF and analysis performed at p9 (p7/9). Control animals were
      PBS injected. At the time of analysis retinal flatmounts were prepared and
      stained with Griffonia lectin and activated caspase-3. The retinal peripheral
      avascular area was measured and number of apoptotic cells counted. In vitro,
      human retinal microvascular endothelial cells (RMVECs) were cultured in media
      containing LIF, with and without neutralizing antibody to LIF. Cells were stained
      with activated caspase-3 and apoptotic cells counted. Proliferation was measured
      by counting cell numbers, and cell cycle stage was determined using propidium
      iodide staining and FACS analysis. LIF injected either IP or IV had no effect on
      body weight or total retina area, but significantly increased the peripheral
      retinal avascular area. In both IP and IV injected groups there was no difference
      in the number of apoptotic cells between PBS- or LIF-injected groups; although in
      the p7/9 retinas, both injected groups had significantly more apoptotic cells
      than the non-injected group. In vitro, there was no effect of LIF on RMVEC
      apoptosis; however, cell counts were significantly lower in the LIF-treated
      group. Antibody to LIF restored the cell counts to untreated levels. LIF reduced
      the number of cells in S phase. LIF attenuates retinal vascular development in
      vivo through growth arrest, and not apoptosis, of endothelial cells.

PMID- 16643898
TI  - Requirement of CD80+ costimulation for rejection of ocular tumors and termination
      of immune privilege.
AB  - Immune privilege in the anterior chamber of the eye is very effective at
      preventing elimination of ocular tumors that express weak tumor antigens. We
      previously demonstrated that DBA/2 mice immunized in the flank with a P815 tumor
      cell vaccine that expressed CD80/IL-12 was unable to terminate immune privilege
      and prevent tumor growth in the anterior chamber. In the present study, we
      determined whether expression of costimulatory signals on tumor cells injected
      via an ocular route would terminate immune privilege. We observed that CD80
      positive tumors were always rejected from the anterior chamber. However, the
      pattern of tumor rejection was dramatically different depending upon whether the
      mice were either naive, or immunized in flank against the tumor cells. Naive mice
      that received an anterior chamber injection of CD80-positive tumors did not
      develop immune privilege and displayed strong delayed hypersensitivity (DH)
      against the tumor cells. Moreover, the ocular tumors were rejected by ischemic
      necrosis that induced atrophy of the eye and phthisis. When immunized mice
      received an identical injection of tumor cells in the anterior chamber, they also
      did not develop immune privilege and displayed strong DH. However, tumor
      rejection was considerably different and occurred without destruction of normal
      ocular tissue, or phthisis. To determine if immune privilege was restored in
      these eyes, mice received a second injection of P815 cells (CD80-negative) into
      the anterior chamber 2weeks after the first CD80-positive tumors were eliminated.
      Surprisingly, immune privilege was not restored and the P815 tumors were
      eliminated completely, again without phthisis. We conclude that specific
      rejection of ocular tumors with minimal destruction of the eye requires systemic
      immunization and expression of CD80 costimulatory signals on tumors within the
      eye.

PMID- 16643899
TI  - Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine
      expression, MAPK activation in the corneal epithelium in experimental dry eye.
AB  - We investigated the effects of corticosteroid and doxycycline on expression of
      matrix metalloproteinase (MMP)-9 and inflammatory cytokines and activation of
      mitogen-activated protein kinase (MAPK) signaling pathways, c-jun N-terminal
      kinases (JNK), extracellular-regulated kinases (ERK) and p38, in experimental
      murine dry eye. Experimental dry eye (EDE) was created in C57BL6 mice, with or
      without or topical treatment consisting of 1% methylprednisolone, 0.025%
      doxycycline or balanced salt solution four times per day. MMP-9 expression in the
      cornea epithelia was evaluated by laser scanning confocal microscopy. Gelatinase
      activity in the cornea was evaluated by in situ zymography and MMP-9 activity in
      tear washings was evaluated by gelatin zymography. Total and phosphorylated MAPKs
      (JNK1/2, ERK1/2, p38) were detected by Luminex immunobead assay. Levels of MMP-9,
      interleukin (IL)-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha RNA
      transcripts were evaluated by real-time PCR. MMP-9 immunoreactivity was localized
      to the apical corneal epithelial cell membranes in normal control eyes.
      Desiccating stress significantly increased production of MMP-9 by the corneal
      epithelium and increased its activity in the corneal epithelium and tear fluid.
      Dryness also increased expression of IL-1alpha, IL-1beta and TNF-alpha mRNA and
      stimulated phosphorylation of JNK1/2, ERK1/2 and p38 MAPKs in the corneal
      epithelium. Both methylprednisolone and doxycycline reduced expression and
      activity of MMP-9, decreased levels of inflammatory cytokines transcripts and
      reduced activation of MAPKs in the corneal epithelium in response to EDE.
      Desiccating stress stimulates expression of MMP-9, IL-1alpha, IL-1beta and TNF
      alpha mRNA , as well as activates MAPK signaling pathways in the corneal
      epithelium. Both corticosteroid and doxycycline suppressed this molecular stress
      response.

PMID- 16643900
TI  - Role of the unfolded protein response (UPR) in cataract formation.
AB  - Cataract is a multifactorial disease, and a large variety of stressors induce
      cataracts. Many cataractogenic stressors and endoplasmic reticulum (ER) stressors
      induce the unfolded protein response (UPR) in various cell types. The UPR is
      known to produce reactive oxygen species (ROS) prior to the inducement of
      apoptosis. We investigated whether ER stressors induce the UPR in lens epithelial
      cells (LECs) or whole rat lenses. Our results showed that higher levels of ER
      stressors activated Bip/GRP78, ATF4, and caspase-12. In addition, ROS were
      produced, free glutathione was decreased, and apoptosis was induced. LECs in the
      mitotic zone were the most susceptible to the UPR while the central LECs were the
      most resistant. The UPR induced the production of ROS in the ER and probably in
      the mitochondria. The detectable ROS production in cultured lenses is limited to
      the epithelial cells. These findings indicate that ER stressors induce the UPR in
      LECs with and without the induction of apoptosis, and we conclude that the UPR is
      probably one of the initiating factors of many types of cataracts.

PMID- 16643901
TI  - Multiple stem cell traits of expanded rat bone marrow stromal cells.
AB  - Bone marrow stromal cells (BMSC) exhibit many traits of a stem cell population.
      Knowing that BMSC have the ability to self-renew, proliferate and differentiate
      into a variety of cell types, questions may arise as to whether these traits
      differ between the cells that have different expansion times. In this study, we
      examined the stem cell potentiality of BMSC through their characterization,
      proliferative capacity and the ability to differentiate into multiple lineages in
      the cultured 2nd passage cells and 10th passage cells. The results were as
      follows: (1) the 10th passage cells had a larger and more flatted morphology than
      the 2nd passage cells and also exhibited a decreased labeling for BMSC-related
      antigens such as CD90, CD73. (2) The cell proliferative capacity was
      approximately 2 times greater in the 2nd passage cells, and the apoptosis
      phenomenon was detected in the 10th passage cells. (3) The ability to
      differentiate into mesodermal tissue (osteocytes, adipocytes), as well as into
      ectodermal tissue (neurons) was more effective in the 2nd passage cells. Taken
      together, early stage BMSC would be a valuable cell source for various in vitro
      applications, as well as cell therapy.

PMID- 16643902
TI  - The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and degradation of
      SOCS6 associated proteins.
AB  - The suppressor of cytokine signaling (SOCS) proteins are thought to exert their
      function through the recruitment of interacting-proteins to the
      ubiquitin/proteasome degradation pathway. All SOCS proteins bind an Elongin BC E3
      ubiquitin ligase complex through the common Socs-box. Here, we show that haem
      oxidized IRP2 ubiquitin ligase-1 (HOIL-1), another E3 ubiquitin ligase, interacts
      with SOCS6. The Ubl domain of HOIL-1 and the SH2 and Socs-box domains of SOCS6
      are required for the interaction. HOIL-1 expression stabilizes SOCS6 and induces
      the ubiquitination and degradation of proteins associated with SOCS6. These data
      suggest that SOCS proteins may interact with different E3 ubiquitin ligases in
      addition to a common Elongin BC E3 complex.

PMID- 16643903
TI  - Mycothiol-dependent mycobacterial response to oxidative stress.
AB  - The effect of exogenous oxidative stress on mycothiol (MSH) levels and redox
      balance was investigated in mycobacteria. Both the thiol-specific oxidant diamide
      and hydrogen peroxide induced up to 75% depletion of MSH to form the disulfide
      form, mycothione (MSSM), in Mycobacterium bovis BCG. In comparison, Mycobacterium
      smegmatis, a saprophytic mycobacterium, displays a greater tolerance towards
      these oxidants, reflected by the lack of fluxes in MSH levels and redox ratios
      upon oxidative stress treatments. The basal ratio of MSH to MSSM was established
      to be 50:1 in M. bovis BCG and 200:1 in M. smegmatis.

PMID- 16643904
TI  - Binding of antibiotic amphotericin B to lipid membranes: a 1H NMR study.
AB  - The (1)H NMR technique was applied to study binding of AmB, an antifungal drug,
      to lipid membranes formed with egg yolk phosphatidylcholine. The analysis of (1)H
      NMR spectra of liposomes, containing also cholesterol and ergosterol (at 40
      mol%), shows that AmB binds preferentially to the polar headgroups. Such a
      binding restricts molecular motion of the choline fragment in the hydrophilic
      region at the surface of liposomes but increases the segmental motional freedom
      in the hydrophobic core. The same effects are also observed in the sterol
      containing membranes, except that the effect on the hydrophobic core was
      exclusively observed in the membranes containing ergosterol.

PMID- 16643905
TI  - Involvement of Na+/H+ exchanger in the calcium signaling in epimastigotes of
      Trypanosoma cruzi.
AB  - We studied the effect of Na(+) extracellular on Ca(2+) mobilization from
      intracellular store evoked by carbachol in Trypanosoma cruzi. We report that slow
      component of Ca(2+) signaling evoked by agonist is dependent on extracellular
      Na(+) but not on InsP(3) increase. Moreover, this Ca(2+) signaling progressively
      increased when pH of the medium changed from 7.0 to 7.8. In addition, we found
      that it was regulated by PKC. The agonist was also able to induce the
      alkalinization of the acidic compartment, and both Ca(2+) signaling and
      alkalinization were inhibited by the EIPA-inhibitor of the Na(+)/H(+) exchanger.
      These results demonstrated the alkalinization of acidic vacuoles and PKC are
      involved in the triggering of the epimastigote Ca(2+) signaling.

PMID- 16643906
TI  - Visualization and sensing of intermolecular interactions with two-color
      fluorescent probes.
AB  - We developed a new generic fluorescence sensing technology based on the change of
      relative intensities between two well-separated emission bands of the novel
      functional 3-hydroxychromone (3HC) dyes. A greatly enhanced self-calibrating
      wavelength-ratiometric response is obtained to all major types of non-covalent
      interactions that can be used in sensing--to polarity, hydrogen bonding ability
      and to local electrostatic fields. This technology may find a broad range of
      applications--from homogeneous assays in solutions to microarrays, microfluidic
      devices, nanosensors and whole cell imaging systems. It allows transforming
      micelles or phospholipid vesicles into nanosensor devices. In cellular research a
      high sensitivity to membrane potentials can be obtained and the membrane changes
      during apoptosis detected.

PMID- 16643907
TI  - Crystal structure of dimeric FabZ of Plasmodium falciparum reveals conformational
      switching to active hexamers by peptide flips.
AB  - The crystal structure of beta-hydroxyacyl acyl carrier protein dehydratase of
      Plasmodium falciparum (PfFabZ) has been determined at a resolution of 2.4 A.
      PfFabZ has been found to exist as a homodimer (d-PfFabZ) in the crystals of the
      present study in contrast to the reported hexameric form (h-PfFabZ) which is a
      trimer of dimers crystallized in a different condition. The catalytic sites of
      this enzyme are located in deep narrow tunnel-shaped pockets formed at the dimer
      interface. A histidine residue from one subunit of the dimer and a glutamate
      residue from the other subunit lining the tunnel form the catalytic dyad in the
      reported crystal structures. While the position of glutamate remains unaltered in
      the crystal structure of d-PfFabZ compared to that in h-PfFabZ, the histidine
      residue takes up an entirely different conformation and moves away from the
      tunnel leading to a His-Phe cis-trans peptide flip at the histidine residue. In
      addition, a loop in the vicinity has been observed to undergo a similar flip at a
      Tyr-Pro peptide bond. These alterations not only prevent the formation of a
      hexamer but also distort the active site geometry resulting in a dimeric form of
      FabZ that is incapable of substrate binding. The dimeric state and an altered
      catalytic site architecture make d-PfFabZ distinctly different from the FabZ
      structures described so far. Dynamic light scattering and size exclusion
      chromatographic studies clearly indicate a pH-related switching of the dimers to
      active hexamers.

PMID- 16643908
TI  - YIL042c and YOR090c encode the kinase and phosphatase of the Saccharomyces
      cerevisiae pyruvate dehydrogenase complex.
AB  - In Saccharomyces cerevisiae the pyruvate dehydrogenase (PDH) complex is regulated
      by reversible phosphorylation of its Pda1p subunit. We here provide evidence that
      Pda1p is phosphorylated by the mitochondrial kinase Yil042cp. Deletion of
      YOR090c, encoding a putative mitochondrial phosphatase, results in a decreased
      PDH activity, indicating that Yor090cp acts as the corresponding PDH phosphatase.
      We demonstrate by means of blue native gel electrophoresis and tandem affinity
      purification that both enzymes are associated with the PDH complex.

PMID- 16643909
TI  - Absence of follicular phase defect in women with recurrent miscarriage.
AB  - OBJECTIVE: The study was designed to compare the follicular phase of women with
      recurrent pregnancy loss and a healthy control group. It is possible that a
      defective or aberrant follicular phase may be associated with poor oocyte quality
      leading to a production of an embryo with compromised quality and hence early
      pregnancy loss. DESIGN: Prospective case-control study. SETTING: A tertiary care
      hospital of Sheffield, UK. PATIENT(S): Thirty-four women with recurrent
      miscarriage and 10 women with no previous history of miscarriage and regular
      menstrual cycles (control group) were recruited. INTERVENTION(S): The
      characteristics studied included Doppler assessment of blood flow to the follicle
      and the endometrium. Simultaneously, serum concentrations of biochemical markers
      such as anti-Mullerian hormone, inhibin B, FSH, LH, and P were compared in the
      two groups. MAIN OUTCOME MEASURE(S): Differences in the two groups. RESULT(S): We
      were unable to detect significant differences in various biochemical and
      ultrasound measurements in the follicular phase between women with recurrent
      miscarriage and a control group; however, the expected correlation between
      ovarian and pituitary hormones, which was observed in the control group, was
      absent in women with recurrent miscarriage. CONCLUSION(S): There may be subtle
      derangements of the feedback mechanism responsible for regulation of follicle
      development in this group of women. However, there were no obvious differences in
      the follicular phase of women with recurrent miscarriage and a healthy control
      group.

PMID- 16643910
TI  - Expression of vascular endothelial growth factor messenger ribonucleic acid and
      protein in human preimplantation embryos.
AB  - In contrast to a previous report by Krussel et al., with the inclusion of larger
      numbers of unfertilized oocytes and normal embryos and more sensitive
      immunofluorescence, this study shows that expression of vascular endothelial
      growth factor messenger ribonucleic acid can be detected from the oocyte to the
      blastocyst stage and that protein can be detected from the 3-cell stage to the
      blastocyst stage in human preimplantation embryos.

PMID- 16643911
TI  - Membranous and structural damage that occur during cryopreservation of human
      sperm may be time-related events.
AB  - OBJECTIVE: To evaluate sperm cryopreservation-induced injuries using sperm plasma
      membrane protein P34H and alpha-tubulin as two different subcellular compartment
      markers. DESIGN: Prospective experimental study. SETTING: Academic hospital
      research center and fertility clinic. PATIENT(S): Semen samples obtained from
      healthy donors attending the fertility clinic. Sperm samples were either directly
      processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and Western blot experiments (control group) or cryopreserved in liquid
      nitrogen for different periods of time before being analyzed. INTERVENTION(S):
      SDS-PAGE, Western blotting, and densitometric quantification of P34H and alpha
      tubulin before and after cryopreservation. MAIN OUTCOME MEASURE(S): Changes in
      protein quantification between the different groups as a result of sperm
      cryopreservation. RESULT(S): In the 31 sperm samples processed for P34H
      evaluation, a 50% decrease is observed after sperm cryopreservation as compared
      to the control group. The alpha-tubulin immunoblotting of 41 sperm samples
      revealed a 200% increase in the protein detection in the group of cryopreserved
      sperm as compared to the control group. Contrary to the P34H detection, this
      change in alpha-tubulin immunodetected levels appears to be related to the
      cryopreservation period as it increases during storage. CONCLUSION(S): These
      findings indicate that cryopreservation of human semen induces damages at
      different cellular levels. Moreover, some cryoinjuries are immediate although
      others seem to take place over time stored in liquid nitrogen.

PMID- 16643912
TI  - Preliminary counseling with age-related fertility rates does not influence
      whether women undergo reversal of sterilization.
AB  - Our objective was to assess the influence of preliminary counseling that provided
      information about age-related fertility rates on the decision of women to undergo
      reversal of sterilization. There was no apparent influence; this raises the
      question as to whether couples seeking fertility therapy base their decision
      making on factual information provided by the clinician.

PMID- 16643913
TI  - Mediation of the behavioral, endocrine and thermoregulatory actions of ghrelin.
AB  - The action of ghrelin on telemetrically recorded motor activity and the
      transmission of the effects of this neuropeptide on spontaneous and exploratory
      motor activity and some related endocrine and homeostatic parameters were
      investigated. Different doses (0.5-5 microg) of ghrelin administered
      intracerebroventricularly caused significant increases in both square crossing
      and rearing activity in the "open-field" apparatus, while only the dose of 5
      microg evoked a significant increase in the spontaneous locomotor activity
      recorded by telemetry. Ghrelin also induced significant increases in
      corticosterone release and core temperature. To determine the transmission of
      these neuroendocrine actions, the rats were pretreated with different
      antagonists, such as a corticotropin-releasing hormone (CRH) antagonist (alpha
      helical CRH(9-41)), the nitric oxide synthase inhibitor Nomega-nitro-L-arginine
      methyl ester (L-NAME), haloperidol, cyproheptadine or the cyclooxygenase
      inhibitor noraminophenazone (NAP). The open-field and biotelemetric observations
      revealed that the motor responses were diminished by pretreatment with the CRH
      antagonist and haloperidol. In the case of HPA (hypothalamic pituitary adrenal)
      activation, only cyproheptadine pretreatment proved effective; haloperidol and L
      NAME did not modify the corticosterone response. NAP had only a transient, while
      cyproheptadine elicited a more permanent impact on the hyperthermic response
      evoked by ghrelin; the other antagonists proved to be ineffective. The present
      data suggest that both CRH release and dopaminergic transmission may be involved
      in the ghrelin-evoked behavioral responses. On the other hand, ghrelin appears to
      have an impact on the HPA response via a serotonergic pathway and on the
      hyperthermic response via a cyclooxygenase and a serotonergic pathway.

PMID- 16643914
TI  - Ghrelin concentrations and cardiac vagal tone are decreased after pharmacologic
      and cognitive-behavioral treatment in patients with bulimia nervosa.
AB  - Patients with bulimia nervosa (BN) have bulimic and depressive symptoms, which
      have been associated with abnormalities in the neuroendocrine and vagal systems.
      Subjects included twenty-four female drug-free outpatients with BN that were
      selected from patients seeking treatment for eating behavior in our hospital
      along with twenty-five age-matched healthy females who served as controls. We
      investigated ghrelin and leptin levels, cardiac vagal tone and sympathovagal
      balance, frequency of sets of binge-eating and vomiting episodes per week and the
      Profile of Mood States (POMS) depression scale in BN before and after a 16-week
      administration of the serotonin selective reuptake inhibitor (SSRI) paroxetine
      combined with cognitive-behavioral therapy. Compared to controls, the BN group
      had higher ghrelin levels and resting cardiac vagal tone, and lower leptin levels
      and resting cardiac sympathovagal balance before treatment, although there was a
      significant difference between the two groups for the body mass index (BMI). The
      elevated ghrelin levels (301.7 +/- 18.9 pmol/l, mean +/- SEM vs. 202.8 +/- 15.6
      pmol/l, P < 0.01), cardiac vagal tone (2246.4 +/- 335.5 ms(2) vs. 1128.5 +/-
      193.3 ms(2), P < 0.01), frequency of sets of binge-eating and purging episodes
      and T scores for the POMS depression scale were all significantly decreased after
      treatment despite similar BMI, percent body fat and leptin levels. In close
      association with cardiac vagal function and ghrelin recoveries, abnormal eating
      behavior and depressive symptoms improved, indicating the usefulness of these
      indexes in the assessment of clinical condition and therapeutic efficacy in BN.

PMID- 16643915
TI  - Neuropeptide binding reflects convergent and divergent evolution in species
      typical group sizes.
AB  - Neuroendocrine factors that produce species differences in aggregation behavior
      ("sociality") are largely unknown, although relevant studies should yield
      important insights into mechanisms of affiliation and social evolution. We here
      focused on five species in the avian family Estrildidae that differ selectively
      in their species-typical group sizes (all species are monogamous and occupy
      similar habitats). These include two highly gregarious species that independently
      evolved coloniality; two territorial species that independently evolved
      territoriality; and an intermediate, modestly gregarious species that is a
      sympatric congener of one of the territorial species. Using males and females of
      each species, we examined binding sites for (125)I-vasoactive intestinal
      polypeptide (VIP), (125)I-sauvagine (SG; a ligand for corticotropin releasing
      factor, CRF, receptors) and a linear (125)I-V(1a) vasopressin antagonist (to
      localize receptors for vasotocin, VT). VIP, CRF and VT are neuropeptides that
      influence stress, anxiety and/or various social behaviors. For numerous areas
      (particularly within the septal complex), binding densities in the territorial
      species differed significantly from binding in the more gregarious species, and
      in most of these cases, binding densities for the moderately gregarious species
      were either comparable to the two colonial species or were intermediate to the
      territorial and colonial species. Such patterns were observed for (125)I-VIP
      binding in the medial bed nucleus of the stria terminalis, medial septum,
      septohippocampal septum, and subpallial zones of the lateral septum; for (125)I
      SG binding in the infundibular hypothalamus, and lateral and medial divisions of
      the ventromedial hypothalamus; and for the linear (125)I-V(1a) antagonist in the
      medial septum, and the pallial and subpallial zones of the caudal lateral septum.
      With the exception of (125)I-SG binding in the infundibular hypothalamus, binding
      densitites are positively related to sociality.

PMID- 16643916
TI  - Progestin facilitation of lordosis in rodents involves adenylyl cyclase activity
      in the ventral tegmental area.
AB  - Increasing cAMP, or activating dopamine type 1 (D(1)) or GABA(A)/benzodiazepine
      receptor complexes (GBRs), in the ventral tegmental area (VTA) enhances lordosis
      of rodents. Whether D(1)- and/or GBR-mediated increases in progestin-facilitated
      lordosis involve the cAMP-synthesizing enzyme, adenylyl cyclase, in the VTA, was
      investigated. In Experiment 1, ovariectomized estradiol (E(2); 10 microg at h
      0)+progesterone (P; 250 microg at h 45)-primed hamsters first received bilateral
      infusions of the adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine (DDA; 12
      microM/side), or vehicle, and then were infused with the D(1) agonist, SKF38393
      (100 ng/side), the GBR agonist, muscimol (100 ng/side), or vehicle, to the VTA.
      Lordosis was evaluated before and 30 min after each infusion. In Experiment 2,
      ovariectomized, E(2)-primed (10 microg at h 0) rats received VTA infusions of DDA
      (12 microM/side) or vehicle; SKF38393 (100 ng/side), muscimol (100 ng/side), or
      vehicle; and the neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha
      THP; 100 or 200 ng/side), or beta-cyclodextrin vehicle. Lordosis was assessed
      before the series of infusions, immediately after drug infusions and 10 or 60 min
      after 3alpha,5alpha-THP infusions. Progestin- or progestin plus SKF38393-or
      muscimol-mediated increases in lordosis were blocked by DDA pretreatment. Thus,
      in the VTA, progestins' membrane action may involve adenylyl cyclase.

PMID- 16643917
TI  - Comments on "Surgical and psychosocial outcomes in the rural injured, a follow up
      study of 2001 earthquake victims" [Int. J. Care Injured 36 (2005) 927-934].

PMID- 16643918
TI  - Delayed primary closure of fasciotomy wounds with Wisebands, a skin- and soft
      tissue-stretch device.
AB  - BACKGROUND: Fasciotomy incisions for limb compartment syndrome usually cannot be
      closed primarily. The conventional method of wound closure with split-thickness
      skin grafting is effective, but it results in an insensate and disfiguring wound
      and is associated with donor site morbidity. We present our experience in delayed
      primary closure of fasciotomy wounds with Wisebands (WB), a skin- and soft tissue
      stretching device. PATIENTS: Between 2000 and 2003, we treated 16 patients with
      extremity fasciotomy wounds for which primary closure was not feasible. RESULTS:
      The Wisebands devices achieved controlled stretching of the wound edges,
      including skin and underlying soft tissue, until primary closure was feasible.
      Fourteen patients (88%) had successful wound closure, two patients (12%) had
      minor wound complications that did not necessitate the removal of the device, and
      two patients had local wound complications (infection, intractable pain) and
      their devices were removed prematurely. Delayed primary closure was achieved at
      the initial surgery using intraoperative skin stretching in 3 of the 14 cases
      (21%). After a 2-year follow-up (1.3-4 years), the treated area showed stable
      scarring with good aesthetic outcome and no functional deficit. CONCLUSIONS: The
      Wisebands device facilitates closure of fasciotomy wounds with low complication
      rates and good functional and aesthetic outcome. Its application is simple and
      safe and requires a short learning curve. Nevertheless, appropriate patient
      selection, intraoperative judgment and close postoperative supervision are
      essential for optimal results.

PMID- 16643919
TI  - The Pakistan earthquake: a British trainee's experience.

PMID- 16643920
TI  - Peripheral nerve palsies associated with closed fractures and dislocations.
AB  - We have studied 178 consecutive cases of 203 patients admitted to this unit
      between 1999 and 2003 with diagnosis of peripheral nerve palsies associated with
      closed fractures and dislocations in the upper and lower limbs. Fifty-one nerves
      were explored, 25 of which were found partly or completely transected.
      Indications for surgery were high-energy transfer injury, severe neuropathic
      pain, failure to progress and a static Tinel's sign. Spontaneous recovery was
      good in only 25 of the 51 non-operated cases of high-energy transfer injury to
      the circumflex, radial and common peroneal nerves. Good spontaneous recovery is
      closely related to low-energy transfer injury, and is associated with an
      advancing Tinel's sign. Absence of the Tinel's sign indicates conduction block;
      neurophysiological investigation confirms it. We stress the particular value of
      the Tinel's sign, and note that severe neuropathic pain indicates continuing
      damage to the nerve and gives a strong reason for operation.

PMID- 16643921
TI  - Tobacco use amongst nursing and physiotherapy students: a cross sectional
      questionnaire survey.
AB  - AIM: The aim of this research was to evaluate the prevalence, knowledge and
      attitudes of tobacco use in the students of the School of Health Sciences in the
      Campus of Ponferrada (University of Leon, Spain). Two-hundred and sixty-six
      (88.3% of respondents) students were assessed by a confidential questionnaire,
      which was distributed, completed by the students and collected in the same
      session. METHODS: This was a descriptive quantitative survey research design to
      examine the tobacco use among nursing and physiotherapy students. RESULTS: The
      global prevalence was 29.3%. In relation to academic courses we have observed
      statistical significance (p=0.006). Therefore students increased tobacco use
      while their training at the school. Seventy (89.7%) of students were smokers
      prior to commencing degree. Nursing students declared were unfamiliar with
      strategies and methods to help people to quit. The first academic course students
      (78.6%) significantly differed (p=0.009) from second and third course. We have
      found scores statistically significant (p=0.04) about the students opinion about
      health professionals social role function. CONCLUSION: Tobacco consumption in
      university health students in the third year was higher than people aged 16-24
      years old reported from the National Health Survey. The findings showed a great
      need to improve the curricular content in the area of tobacco including
      information, prevention, and treatment.

PMID- 16643922
TI  - Genotyping of Toxoplasma gondii by multilocus PCR-RFLP markers: a high resolution
      and simple method for identification of parasites.
AB  - It was generally believed that Toxoplasma gondii had a clonal population
      structure with three predominant lineages, namely types I, II and III. This was
      largely based on genotyping of more than 100 T. gondii isolates originating from
      a variety of human and animal sources in North America and Europe. Recent
      genotyping studies on T. gondii strains from wild animals or human patients from
      different geographical regions revealed the high frequency of non-archetypal
      genotypes, suggesting the overall diversity of the T. gondii population might be
      much higher than we thought. However, as most genotyping studies had relied on a
      few biallelic markers, the resolution and discriminative power of identifying
      parasite isolates were quite low. To date, there is no commonly used set of
      markers to genotype T. gondii strains and it is not feasible to compare results
      from different laboratories. Here, we developed nine PCR-restriction fragment
      length polymorphism markers with each of them capable of distinguishing the three
      archetypal T. gondii alleles in one restriction-enzyme reaction by agarose gel
      electrophoresis. Genotyping 46 T. gondii isolates from different sources using
      these markers showed that they could readily distinguish the archetypal from
      atypical types and reveal the genetic diversity of the parasites. In addition,
      mixed strains in samples could be easily detected by these markers. Use of these
      markers will facilitate the identification of T. gondii isolates in
      epidemiological and population genetic studies.

PMID- 16643923
TI  - Effect of individualizing starting doses of a statin according to baseline LDL
      cholesterol levels on achieving cholesterol targets: the achieve cholesterol
      targets fast with atorvastatin stratified titration (ACTFAST) study.
AB  - AIMS: To investigate whether selecting the starting dose of atorvastatin
      according to baseline and target (<2.6 mmol/L) LDL-cholesterol (LDL-C) values
      would allow high-risk subjects to achieve target LDL-C concentration within 12
      weeks, with the initial dose or a single uptitration. METHODS AND RESULTS: Twelve
      week, prospective, open-label trial that enrolled 2117 high-risk subjects (statin
      free [SF] or statin-treated [ST]). Subjects with LDL-C >2.6 mmol/L (100mg/dL) but
      <or=5.7 mmol/L (220 mg/dL) were assigned a starting dose of atorvastatin (10, 20,
      40 or 80 mg/day) based on LDL-C and status of statin use at baseline, with a
      single uptitration at 6 weeks, if required. There was no washout for ST subjects.
      At study end, 80% of SF (82%, 82%, 83% and 72% with 10, 20, 40 and 80 mg,
      respectively) and 59% of ST (60%, 61% and 51% with 20, 40 and 80 mg,
      respectively) subjects reached LDL-C target. In the ST group, an additional 21
      41% reduction in LDL-C was observed over the statin used at baseline.
      Atorvastatin was well tolerated. CONCLUSION: This study confirms that
      individualizing the starting dose of atorvastatin according to baseline and
      target LDL-C values (i.e. the required LDL-C reduction), allows a large majority
      of high-risk subjects to achieve target safely, within 12 weeks, with the initial
      dose or with a single titration.

PMID- 16643924
TI  - Biomechanical characterization and clinical implications of artificially induced
      crouch walking: Differences between pure iliopsoas, pure hamstrings and
      combination of iliopsoas and hamstrings contractures.
AB  - The purpose of this study was to characterize biomechanically three different
      crouch walking patterns, artificially induced in eight neurologically intact
      subjects and to compare them to selected cases of pathological crouch walking.
      The subjects were equipped with a lightweight mechanical exoskeleton with
      artificial muscles that acted in parallel with hamstrings and iliopsoas muscles.
      They walked at a speed of approximately 1m/s along the walkway under four
      experimental conditions: normal walking (NW), hamstrings contracture emulation
      (HAM), iliopsoas contracture emulation (IPS) and emulation of both hamstrings and
      iliopsoas contractures (IPSHAM). Reflective markers and force platform data were
      collected and ankle, knee and hip-joint angles, moments and powers were
      calculated. HAM and IPSHAM shifted ankle-angle rotation profiles into
      dorsiflexion during midstance compared to IPS and NW where ankle-angle
      trajectories were similar. HAM, IPS and IPSHAM shifted the knee angle of rotation
      profiles into flexion during stance, compared to NW. IPS and IPSHAM shifted hip
      angle of rotation profiles toward pronounced flexion while HAM shifted hip angle
      of rotation profile toward extension, compared to NW. HAM and IPSHAM
      significantly increased ankle moment during midstance, compared to IPS and NW
      where ankle moment profiles were similar. All experimental conditions exhibited
      similar behavior in the knee-moment profiles during midstance while IPS and
      IPSHAM knee-moment profiles exhibited significantly higher knee-extension moment
      during terminal stance and pre-swing. In the hip joint all experimental
      conditions exhibited similar shape of hip moment profiles throughout the gait
      cycle. HAM and IPS kinematic and kinetic patterns were qualitatively compared to
      two selected clinical cases, showing considerable similarity. This implies that
      distinct differences in kinematics and kinetics between HAM, IPS and IPSHAM may
      be clinically relevant in helping determine the relative contribution of
      hamstrings and iliopsoas muscles contractures to particular crouch walking.

PMID- 16643925
TI  - Determination of strain energy function for arterial elastin: Experiments using
      histology and mechanical tests.
AB  - The long-range reversible deformation of vertebrate arteries is primarily
      mediated by elastin networks that endure several million deformation cycles
      without appreciable fatigue. To determine how elastin contributes to the
      composite arterial properties, we studied the three-dimensional microstructure
      and biomechanics of isolated elastin. We initially estimated the sensitivity of
      these studies by comparing two elastin isolation protocols, autoclaving and
      alkali-extraction, and measured their effect on isolated elastin using uniaxial
      tests and histology. These studies show that autoclaved tissues have a trend for
      higher modulus (900.79+/-678.02 kPa) than alkali-extracted samples (417.74+/
      162.23 kPa)albeit with higher collagen-proteoglycan impurities, and (2) greater
      optical density (78.6+/-9.1%) than alkali-extracted groups (46.2+/-5.9%),
      suggesting that autoclaving is superior to alkali-extraction for biomechanical
      tests on elastin. Using these data we show that an isotopic Mooney-Rivlin model
      cannot adequately represent arterial elastin. The neo-Hookean model, with
      coefficient 162.57 (+/-115.44) kPa for autoclaved and 76.94 (+/-27.76) kPa for
      alkali-extracted samples, fits the uniaxial data better. Autoclaved elastins also
      show linear stress-strain response and equal stiffness in circumferential and
      axial directions suggesting equal number of layers in these directions and that
      elastin may help distribute tensile stresses during vessel inflation. Histology
      of autoclaved and control porcine arteries reveals axial elastin fibers in
      intimal and adventitial layers but circumferential medial fibers. We propose an
      orthotropic material symmetry for arterial elastin with two orthogonally oriented
      and symmetrically placed mechanically equivalent fibers. An exact form of the
      constitutive equation will be obtained in a future study.

PMID- 16643926
TI  - Coordination of thumb joints during opposition.
AB  - Thumb opposition plays a vital role in hand function. Kinematically, thumb
      opposition results from composite movements from multiple joints moving in
      multiple directions. The purpose of this study was to examine the coordination of
      thumb joints during opposition tasks. A total of 15 female subjects with
      asymptomatic hands were studied. Three-dimensional angular kinematics of the
      carpometacarpal (CMC), metacarpophalangeal (MCP) and interphalangeal (IP) joints
      were obtained by a marker-based motion analysis system. Thumb opposition revealed
      coordination among joints in a specific direction (inter-joint coordination) and
      among different directions within a joint (intra-joint coordination). In
      particular, linear couplings existed between the flexion and pronation at the CMC
      joint, and between the flexion of the CMC joint and flexion of the MCP joint.
      Principal component analysis showed that only two principal components adequately
      represented the thumb opposition data of seven movement directions. A term
      functional degrees of freedom by virtue of principal component analysis was
      proposed to uncover the extent of movement coordination in functional tasks.

PMID- 16643927
TI  - Effect of temperature on the retention of ionizable compounds in reversed-phase
      liquid chromatography: application to method development.
AB  - The analysis of pharmaceutical compounds is often a difficult challenge which
      requires mathematical tools to improve the quality of the separation method. This
      work is an attempt to rationalize the anomalous variation of the logarithm of the
      retention factor with temperature in case of ionizable compounds. The effect of
      temperature on ionizable compounds was studied within a large range of
      temperature, ranging from 30 to 130 degrees C. The determination of the so-called
      chromatographic pKa and the study of its variation with temperature allow to
      explain why the forms of the van't Hoff curves are so different depending on the
      type of solute, the type of buffer and the type of the mobile phase. A retention
      model along with a computation procedure is proposed to optimize both temperature
      and mobile phase composition and to provide good and robust conditions as shown
      by illustrative examples.

PMID- 16643928
TI  - Study on capillary electrophoresis-amperometric detection profiles of different
      parts of Morus alba L.
AB  - A high-performance capillary electrophoresis with amperometric detection (CE-AD)
      method has been developed for the determination of the pharmacologically active
      ingredients in different parts of Morus alba L. after a relatively simple
      extraction procedure. This method was also used in the comparison of bioactive
      constituent difference in the five parts, based on their electropherograms or
      characteristic "CE-AD profiles". The effects of several factors such as the
      acidity and concentration of running buffer, separation voltage, applied
      potential and injection time were investigated to find the optimum conditions.
      Method detection limits (S/N = 3) ranged from 1.5 x 10(-7) to 1.4 x 10(-8)g/mL
      for all 10 analytes, and the assay results were satisfactory.

PMID- 16643929
TI  - A comparison of three algorithms for chromatograms alignment.
AB  - In this paper the performance of three alignment algorithms, correlation
      optimized warping, parametric time warping and semi-parametric time warping, is
      compared on real chromatograms. Among these, parametric time warping is the
      simplest and fastest; generally less than 1s is required to align two
      chromatograms. It does not require the optimization of input parameters and
      allows the alignment of peak shifts in only one direction, or non-complex peak
      shifts in both directions. With correlation optimized warping and semi-parametric
      time warping complex peak shifts in both directions can be corrected but at the
      expense of the optimization of two input parameters. Semi-parametric time warping
      requires the selection of the proper number of B-splines in the warping function
      and, if necessary, the optimization of the penalty parameter. Often the default
      values can be used to obtain aligned signals. The optimization of the input
      parameters for correlation optimized warping (section length, slack) is not easy
      and time-consuming. Moreover, dependent on the input parameters, the computation
      time of the correlation optimized warping algorithm can be twice as long as for
      semi-parametric time warping for which computation times up to 23 s are required.
      However, the performance of both algorithms is equally good considering the
      improvement of the precision of the peak retention times and correlation
      coefficients between the chromatograms, after alignment. For the data aligned in
      this study, the average retention time precision and the lowest correlation
      before warping were 14 and 0.17, and were improved to three and 0.83, and six and
      0.87 after warping, with correlation optimized warping and semi-parametric time
      warping, respectively.

PMID- 16643930
TI  - Coupled two-step microextraction devices with derivatizations to identify
      hydroxycarbonyls in rain samples by gas chromatography-mass spectrometry.
AB  - Coupling a two-step liquid-phase microextraction (LPME) with O-(2,3,4,5,6
      pentafluorobenzyl)-hydroxylamine/bis(trimethylsilyl)trifluoroacetamide
      (PFBHA)/(BSTFA) derivatization was developed to detect hydroxycarbonyls in
      rainwater samples using gas chromatography-mass spectrometry (GC-MS). LPME
      provides a fast and inexpensive pre-concentration, and miniaturized extraction to
      analyze the target compounds rainwater samples. Derivatization techniques offer a
      clear method to identify target compounds. The hydroxycarbonyls were determined
      using two-step derivatizations. Dynamic-LPME was applied in the first
      derivatization, and head-space single drop derivatization was employed in the
      second reaction. The LODs varied from 0.023 to 4.75 microg/l. The calibration
      curves were linear for at least two orders of magnitude with R2>or=0.994. The
      precision was within 6.5-12%, and the relative recoveries in rainwater were more
      than 89% (the amount added ranged from 0.3 to 15 microg/l). A field sample was
      found to contain 2.54 microg/l of hydroxyacetone and 0.110 microg/l of 3-hydroxy
      2-butanone. Hydroxyacetone was also detected in one of the tested samples at a
      concentration of 2.39 microg/l.

PMID- 16643931
TI  - Electrophoretic behavior of plasmid DNA in the presence of various intercalating
      dyes.
AB  - In the present study, the electrophoretic behavior of linear, supercoiled and
      nicked circular plasmid DNA in the presence of various intercalating dyes was
      characterized using pGL3 plasmid DNA as a model. The enzymatic digestion of pGL3
      plasmid DNA with HindIIIwas monitored by capillary electrophoresis coupled with
      laser-induced fluorescence detection (CE-LIF). Nicked circular plasmid DNA was
      found to be relatively sensitive to enzymes, and was almost digested into the
      linear conformer after 10-min incubation, indicating that nicked circular plasmid
      DNA has little chance of targeting and entering the cell nucleus. Partly digested
      plasmid DNA containing only linear and supercoiled conformers can be used as a
      standard to confirm the migration order of plasmid DNA. In methylcellulose (MC)
      solution with YO-PRO-1 or YOYO-1, linear plasmid DNA eluted first, followed by
      supercoiled and nicked plasmid DNA, and nicked plasmid DNA eluted as a broad
      peak. With SYBR Green 1, nicked plasmid DNA eluted first as three sharp peaks,
      followed by linear and supercoiled plasmid DNA. The nuclear plasmid DNA from two
      transfected cell lines was successfully analyzed using the present procedure.
      Similar results were obtained with an analysis time of seconds using microchip
      electrophoresis with laser-induced fluorescence detection (mu-CE-LIF). To our
      knowledge, these results represent the first reported analysis of nuclear plasmid
      DNA from transfection cells by CE-LIF or mu-CE-LIF without pre-preparation,
      suggesting that the present procedure is a promising alternative method for
      evaluating transfection efficiency of DNA delivery systems.

PMID- 16643932
TI  - Nonaqueous capillary electrophoresis method for the enantiomeric purity
      determination of S-timolol using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta
      cyclodextrin: validation using the accuracy profile strategy and estimation of
      uncertainty.
AB  - Nonaqueous capillary electrophoresis (NACE) was successfully applied to the
      enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O
      methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) as chiral selector. With a
      background electrolyte made up of a methanolic solution of 0.75 M formic acid, 30
      mM potassium camphorsulfonate and containing 30 mM HDMS-beta-CD, the
      determination of 0.1% of R-timolol in S-timolol could be performed with an
      enantiomeric resolution of 8.5. Pyridoxine was selected as internal standard. The
      NACE method was then fully validated by applying a novel strategy using accuracy
      profiles. It is based on beta-expectation tolerance intervals for the total
      measurement error which includes trueness and intermediate precision. The
      uncertainty of measurements derived from beta-expectation tolerance intervals was
      estimated at each concentration level of the validation standards. To confirm the
      suitability of the developed and validated method, several real samples of S
      timolol maleate containing R-timolol maleate at different concentrations were
      analysed and the results were compared to those obtained by liquid
      chromatography.

PMID- 16643933
TI  - Synthesis, characterization, and sorption properties of silica gel-immobilized
      pyrimidine derivative.
AB  - 5-Benzylidene-2-thiobarbituric acid (BzTBA), a pyrimidine derivative, was used to
      modify the surface of silica gel-chloropropyltrimethoxysilane (Si-Cl) via
      chemical immobilization to produce a new pyrimidine silica phase (Si-BzTBA).
      Identification of the surface modification was characterized and performed on the
      basis of infrared as well as elemental analysis. Thermal desorption method was
      found to give 0.129-0.143 mmol g(-1) as surface coverage values. Metal sorption
      properties of Si-BzTBA were also studied and the evaluated results refer to the
      high metal sorption of Si-BzTBA for copper(II), mercury(II), cadmium(II), and
      lead(II) with the same order. These four Si-BzTBA-metal complexes were also
      synthesized and the stoichiometric ratios were identified as 1:1 except lead
      complex was found to give a 1:2 ratio. Electron impact-mass spectrometric
      analysis (EI-MS) with 70 eV ionization energy was used as a potential thermal
      method for the confirmation of surface modification of Si-BzTBA and its metal
      complexes based on fragmentation elucidation of thermally desorbed ion peaks. The
      EI-MS of Si-BzTBA was found to show several characteristic fragment ion peaks
      that are directly related to the chemical binding of BzTBA to SiCl phase.
      Differential scanning calorimetry study (DSC) was also performed to evaluate the
      various kinetic and thermodynamic parameters of thermal degradation processes and
      have been enumerated. The results of EI-MS and DSC are very similar in many
      respects.

PMID- 16643934
TI  - One-dimensional assemblies of platinum nanoparticles on a graphite surface using
      nonionic/ionized mixed hemicylindrical micelle templates.
AB  - One-dimensional (1-D) self-assemblies of Pt nanoparticles on a graphite surface
      have been synthesized via a template-directed sintering process of individual
      nanoparticles, using nonionic/cationic mixed hemicylindrical micelle templates of
      dodecyldimethylamine oxide surfactant at graphite/solution interfaces. The
      dimension and morphology of Pt nanoparticles can be widely controlled by the
      concentration of Pt ions equivalent to the mixing ratio of nonionic and cationic
      species in the surfactant micelle. This approach could be extended to fabricate a
      wide range of self-assembling metallic nanostructures on surfaces using various
      nonionic/cationic mixed micelle-like self-assemblies carrying metal ions at
      interfaces, while providing a fundamental insight into a 1-D self-assembly from
      individual nanoparticles.

PMID- 16643935
TI  - Successive interaction of pairs of soluble organics with nanosilica in aqueous
      media.
AB  - Successive interaction of different pairs of water-soluble polymers
      (poly(ethylene glycol) (PEG), poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol)
      (PVA)), proteins (bovine serum albumin (BSA), ovalbumin, gelatin, and ossein),
      and smaller organics such as lecithin (1-stearoyl-2-oleoyl phosphatidylcholine,
      SOPC) and Aethonium (1,2-ethylene-bis(N-dimethyl carbodecyl oxymethyl) ammonium
      dichloride) with nanosilicas A-300 (S(BET)=232 and 297 m(2) g(-1)) and A-50
      (S(BET)=52 m(2)g(-1)) was studied using dynamic light scattering, adsorption, and
      infrared (FTIR) spectroscopy methods. Time-dependent rearrangement of particle
      size distributions (PSDs) depicts appearance of both smaller and larger
      aggregates for silica/PEG(I-first adsorbate)/BSA(II-second adsorbate) and
      silica/PVP(I)/BSA(II) (i.e., BSA adsorbs onto PEG/silica or PVP/silica) than that
      for silica/organic compound I. However, in the cases of PVA(I)-BSA(II) and PVA(I)
      SOPC(II) a similar effect is not observed because only increased aggregation
      occurs. The successive equilibrium adsorption of similar pairs shows a diminution
      of the adsorption of the second compound (gelatin, ovalbumin) with increasing
      amount of the first adsorbed polymer (PEG or PVP).

PMID- 16643936
TI  - Sequestration of amitriptyline by liposomes.
AB  - We study the uptake of amitriptyline, which is a common cause of overdose-related
      fatalities, in aqueous solutions by 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC) liposomes and liposomes composed of a mixture of DMPC and 1,2-dioleoyl-sn
      glycero-3-[phospho-rac(1-glycerol)] (DOPG) lipids. The effect of drug
      concentration, liposomal charge, pH, salt, and protein presence on the drug
      uptake is investigated using two different methodologies, a precipitation and a
      centrifugation method. Furthermore, the time scale of the drug uptake is studied
      through qualitative observations at high pH and through conductivity measurements
      at neutral pH and found to be <5 s. The results of the quantitative studies show
      that the fractional drug uptake decreases with increasing drug concentration, and
      for a given concentration it increases with the pH and decreases in the presence
      of salt. We find that a larger amount of drug is sequestered by negatively
      charged liposomes (those containing DOPG) than liposomes with no net charge
      (DMPC). We speculate that the mechanism of drug uptake is due to both
      electrostatic interactions as well as hydrophobic effects. The fractional uptake
      by DMPC:DOPG in a 70:30 ratio is as high as 95% in water and about 90% in
      physiological buffer. The fractional uptake is also measured in presence of 2%
      (w/w) bovine serum albumin (BSA), which is approximately the protein
      concentration in the intercellular fluid. In presence of protein the fractional
      uptakes by 70:30 DMPC:DOPG liposomes and 50:50 DMPC:DOPG liposomes are 82 and
      90%, respectively, at 125 muM drug amitriptyline. In the absence of liposomes,
      67% of the drug is taken up by the protein in a 2% (w/w) BSA, 125 muM
      amitriptyline solution. Thus, addition of 50:50 DMPC:DOPG liposomes reduces the
      free drug concentration by a factor of about 3.5, making them attractive
      candidates for drug detoxification.

PMID- 16643937
TI  - Viscous-gravity spreading of time-varying liquid drop volumes on solid surfaces.
AB  - Viscous-gravity spreading of liquid drops of time-dependent volume over a solid
      surface is considered. A self-similar solution for the drop configuration is
      obtained, in the case the liquid drop volume varies as a power-law function of
      time, along with the spreading laws in both cases of cylindrical and axisymmetric
      geometries. Results compare favorably with published experimental results and
      previous theoretical work. The limitations of the model are discussed, along with
      a comparison with viscous gravity spreading of oil on water. The validity of
      using approximate spreading laws is considered, and an approximate method is
      suggested to provide the dynamics of spreading in the general case where the drop
      volume does not necessarily vary as a power-law function of time.

PMID- 16643938
TI  - Removal of phosphate from aqueous solution by zeolite synthesized from fly ash.
AB  - Fifteen Chinese fly ashes were converted hydrothermally into zeolites, and
      phosphate immobilization capacity (PIC) of the synthesized zeolites and the
      corresponding raw fly ashes were determined using an initial phosphate
      concentration of 1000 mg/L. Results showed that there was a remarkable increase
      in PIC (from 1.2 to 7.6 times) following the synthesis process. Fractionation of
      immobilized phosphorus indicated that Fe+Al-P increased most significantly and
      consistently among all the phosphorus fractions following the conversion of fly
      ash to zeolite. The PIC and Ca+Mg-P were closely related to Ca content (with r
      values of 0.9683 and 0.9651, respectively) rather than Mg content (with r values
      of 0.3920 and 0.3212, respectively). The r values of PIC and Fe+Al-P with Fe
      content (with r values of 0.4686 and 0.6385, respectively) were higher than those
      with Al content (with r values of -0.7857 and -0.3770, respectively). Although
      calcium and iron components were mainly involved in phosphate immobilization,
      there was no significant change of Ca and Fe content following the conversion of
      fly ash to zeolite. Increase in dissociated Fe(2)O(3) and specific surface area
      probably accounted for the enhancement in PIC of synthesized zeolites compared
      with corresponding fly ashes. The PIC value of zeolites showed a significant
      correlation with dissociated Fe(2)O(3) (r=0.6186). The specific surface area
      increased 26.0-89.4 times as a result of the conversion of fly ash to zeolite.
      The maximum removal of phosphate occurred within different pH ranges for zeolites
      which were synthesized from high, medium and low calcium fly ashes and this
      behavior was explained by the reaction of phosphate with calcium and iron
      components.

PMID- 16643939
TI  - Fabrication of UV-blocking nanohybrid coating via miniemulsion polymerization.
AB  - A novel convenient approach to fabricate ZnO@polystyrene nanohybrid coating on
      cotton fabrics is reported. The as-prepared core-shell nanohybrid coating was
      characterized by scanning electron microscope (SEM), transmission electron
      microscope (TEM), energy dispersive X-ray (EDX), and UV-blocking. The cotton
      fabrics treated in this study provided ultrahigh UV protection and superior wash
      fastness. Therefore, this new nanohybrid material and its synthesis method are
      highly potential to various functional treatments of flexible surfaces.

PMID- 16643940
TI  - Comment on "Electrorheological behavior of copper phthalocyanine-doped mesoporous
      TiO2 suspensions".
AB  - We comment on the electrorheological (ER) behavior of copper phthalocyanine
      (CuPC)-doped mesoporous TiO(2) suspensions. Our Cole-Cole plot not only fits the
      dielectric spectra of the two CuPC-doped mesoporous TiO(2) templated ER fluids
      with CuPC/cetyltrimethylammonium (CTAB) molar ratios of 0.10 and 0.15,
      respectively, but also provides a better explanation of their polarizability by
      differentiating their ER performance.

PMID- 16643941
TI  - Phase behavior of mixtures of polyoxyethylene(10) stearyl ether (Brij-76), 1
      butanol, isooctane, and mixed polar solvents I. Water and formamide (or N,N
      dimethyl formamide).
AB  - The isothermal phase diagram of the quaternary system polyoxyethylene(10) stearyl
      ether (Brij-76)/1-butanol/isooctane/water has been constructed at 30 degrees C
      with equal amounts of oil and water. A regular fishtail diagram was obtained,
      confirming the establishment of hydrophile-lipophile balance (HLB) in the system.
      Mixing of formamide (FA) [or N,N-dimethyl formamide (DMF)] with water as a
      cosolvent altered the HLB and decreased the solubilization capacity of the
      quaternary system. No three-phase body appeared at high FA or DMF content.
      Similar observations were noted for temperature-induced phase diagrams. The
      effect of DMF was more pronounced than that of FA in reducing the maximum
      solubilization capacity. The results have been summarized on the basis of HLB and
      mutual solubility of the components.

PMID- 16643942
TI  - Kinetics of phosphate adsorption on goethite: comparing batch adsorption and ATR
      IR measurements.
AB  - The adsorption kinetics of phosphate on goethite has been studied by batch
      adsorption experiments and by in situ ATR-IR spectroscopy at different pH,
      initial phosphate concentrations and stirring rates. Batch adsorption results are
      very similar to those reported by several authors, and show a rather fast initial
      adsorption taking place in a few minutes followed by a slower process taking
      place in days or weeks. The adsorption kinetics could be also monitored by
      integrating the phosphate signals obtained in ATR-IR experiments, and a very good
      agreement between both techniques was found. At pH 4.5 two surface complexes, the
      bidentate nonprotonated (FeO)(2)PO(2) and the bidentate protonated (FeO)(2)(OH)PO
      complexes, are formed at the surface. There are small changes in the relative
      concentrations of these species as the reaction proceeds, and they seem to evolve
      in time rather independently. At pH 7.5 and 9 the dominating surface species is
      (FeO)(2)PO(2), which is accompanied by an extra unidentified species at low
      concentration. They also seem to evolve independently as the reaction proceeds.
      The results are consistent with a mechanism that involve a fast adsorption
      followed by a slow diffusion into pores, and are not consistent with surface
      precipitation of iron phosphate.

PMID- 16643943
TI  - Effect of oxygen plasma treatment on the surface properties of tin-doped indium
      oxide substrates for polymer LEDs.
AB  - The effect of oxygen plasma treatment on the surface properties of tin-doped
      indium oxide (ITO) substrates and the changes in surface properties of treated
      ITO substrates with ageing time were investigated by X-ray photoelectron
      spectroscopy (XPS), contact angle and surface free energy measurements.
      Experimental results show that oxygen plasma treatment increases the oxygen
      concentration, decreases the carbon concentration, and enhances the surface free
      energy and polarity, and thereby improves the surface properties of ITO
      substrates. However, the improved ITO surface properties tended to decay and the
      surface free energy decreased, with ageing time. In addition, the ageing effect
      of treated ITO substrates on the performance of polymer light-emitting diodes
      (LEDs) was studied with respect to the driving voltage, electroluminescent
      luminance and efficiency. We observe that the ITO substrates aged for various
      times result in significant differences in optical and electrical characteristics
      which become worse as the ageing time increases. The optical and electrical
      performance of polymer LEDs is closely related to the surface properties of ITO
      substrate and the interface characteristics of ITO/polymer.

PMID- 16643944
TI  - Effect of ion-exchange nanofiber fabrics on water splitting in bipolar membrane.
AB  - In the present study, the effect of ion-exchange fiber fabric made by
      electrospray deposition (ESD) on water splitting in a composite bipolar membrane
      (CBM) was investigated. Cation- and anion-exchange fiber (CEF and AEF) fabrics,
      which were composed of very thin fibers, were prepared by ESD and postdeposition
      chemical modification and then used as the intermediate layer of a CBM. The
      current-voltage characteristics under reverse bias conditions showed that the AEF
      fabrics enhanced water splitting. The water dissociation is accelerated by the
      AEF fabric, which contains both tertiary pyridyl groups and quaternary pyridinium
      groups and has a high specific surface area. On the other hand, the CEF fabric,
      which contains sulfonic acid groups and has an insufficient specific surface
      area, reduced water splitting. These results indicate that fiber fabric with
      catalytic activity and a high surface area obtained by ESD can improve the
      performance of a CBM.

PMID- 16643945
TI  - Biochemical basis of specialization for dispersal vs. reproduction in a wing
      polymorphic cricket: morph-specific metabolism of amino acids.
AB  - The biochemical basis of specializations for dispersal vs. reproduction is an
      understudied aspect of dispersal polymorphism in insects. Using a radiolabelled
      amino acid, we quantified differences in in vivo amino acid metabolism between
      morphs of the wing-polymorphic cricket, Gryllus firmus, that trade-off early age
      reproduction and dispersal capability. Studies were conducted in crickets fed a
      variety of diets expected to influence amino acid and lipid metabolism. On the
      day of molt to adulthood, prior to the morph-specific trade-off between ovarian
      growth and biochemical preparation for flight (e.g. biosynthesis of triglyceride
      flight fuel), morphs did not differ in any aspect of amino acid metabolism.
      However, on day 5 of adulthood, when the morph-specific trade-off between ovarian
      growth and flight fuel production was manifest, the morphs differed substantially
      in each of the three aspects of amino acid metabolism studied: conversion to
      protein, oxidation, and conversion to lipid. Morphs also differed in degree of
      allocation of products of amino acid metabolism to ovaries vs. the soma. Most
      importantly, morphs differed in the relative metabolism of radiolabelled glycine
      through these pathways (i.e. biochemical trade-offs), and in the relative
      allocation of end products of amino acid metabolism to the soma vs. ovaries
      (allocation trade-offs). A functionally important interaction between amino acid
      and lipid metabolism was noted: greater oxidation of amino acids in the flight
      capable morph spared fatty acids for enhanced conversion into triglyceride flight
      fuel. By contrast, greater oxidation of fatty acids by the flightless morph
      spared amino acids for enhanced conversion into ovarian protein. Diet
      significantly affected amino acid metabolism. However, MORPHxDIET interactions
      were rare and morphs differed in amino acid metabolism to a similar degree under
      the range of diets tested.

PMID- 16643946
TI  - Sub-microsecond protein folding.
AB  - We have investigated the structure, equilibria, and folding kinetics of an
      engineered 35-residue subdomain of the chicken villin headpiece, an ultrafast
      folding protein. Substitution of two buried lysine residues by norleucine
      residues stabilizes the protein by 1 kcal/mol and increases the folding rate
      sixfold, as measured by nanosecond laser T-jump. The folding rate at 300 K is
      (0.7 micros)(-1) with little or no temperature dependence, making this protein
      the first sub-microsecond folder, with a rate only twofold slower than the
      theoretically predicted speed limit. Using the 70 ns process to obtain the
      effective diffusion coefficient, the free energy barrier height is estimated from
      Kramers theory to be less than approximately 1 kcal/mol. X-ray crystallographic
      determination at 1A resolution shows no significant change in structure compared
      to the single-norleucine-substituted molecule and suggests that the increased
      stability is electrostatic in origin. The ultrafast folding rate, very accurate X
      ray structure, and small size make this engineered villin subdomain an ideal
      system for simulation by atomistic molecular dynamics with explicit solvent.

PMID- 16643947
TI  - Behavioral inhibition system (BIS), behavioral activation system (BAS) and
      schizophrenia: relationship with psychopathology and physiology.
AB  - OBJECTIVE: The Behavioral Inhibition System (BIS) and the Behavioral Activation
      System (BAS) have been conceptualized as two neural motivational systems that
      regulate sensitivity to punishment (BIS) and reward (BAS). Imbalance in BIS and
      BAS levels has been reported to be related to various forms of psychopathology.
      Since sensitivity to stress has been supposed to be a pathway for the development
      of psychotic symptoms, the aim of this study is to examine BIS and BAS scores in
      schizophrenia and their relationship with psychopathology and physiology. METHOD:
      Forty-two patients with schizophrenia (26 men, 16 women), stable on atypical
      antipsychotics, and 37 healthy controls (17 men, 20 women) were assessed with the
      use of the Behavioral Inhibition and Behavioral Activation scales. Since
      increased average heart rate (HR) and decreased heart rate variability (HRV) have
      been reported in patients with schizophrenia and have been shown to correlate
      with inhibited behaviour, these psychophysiological measures were also obtained.
      The BIS/BAS data and HR/HRV data were both analyzed by a (M)ANOVA. Correlation
      coefficients were computed for associations between BIS/BAS data, HR/HRV data,
      and patient variables. RESULTS: On the BIS, patients showed higher sensitivity to
      threat than control subjects. Higher BIS sensitivity correlated with longer
      duration of illness, and lower negative symptoms on the PANSS. The BAS scores did
      not reveal differences between patients and controls. In patients, low BAS
      sensitivity correlated with low dosage of medication. On the physiological
      measures patients showed a significantly higher HR and lower HRV compared to
      controls, which was limited to clozapine treated patients. No correlations were
      found between HR/HRV scores and BIS/BAS scores or patient variables. CONCLUSIONS:
      Male as well as female patients with schizophrenia are more sensitive to threat
      than healthy controls. This may reflect a trait-related characteristic, and is
      not reflected in state-related psychophysiological measures.

PMID- 16643948
TI  - Childhood traumas and hallucinations: an analysis of the National Comorbidity
      Survey.
AB  - Data from the National Comorbidity Survey were used to estimate the relationship
      between occurrences of childhood trauma and self-reported experiences of
      hallucinations. Variables representing (1) childhood neglect, (2) childhood
      physical abuse, (3) rape under the age of 16, and (4) molestation under the age
      of 16 were used to predict experiences of visual, auditory and tactile
      hallucinations. After controlling for background variables (sex, age, depression,
      family history of depression, urbanicity, income, drug, and alcohol dependence),
      a history of childhood rape and molestation were significantly associated with
      visual, auditory and tactile hallucinations. Additionally, neglect was associated
      with visual hallucinations and physical abuse with tactile hallucinations.
      Experiencing multiple types of trauma was associated with increases in the
      likelihood of reporting each of the three types of hallucinations. Hallucinatory
      experiences are possible indicators of a traumatic childhood history.

PMID- 16643949
TI  - Are there protective treatments for cognitive decline in MS?
AB  - Despite its frequency and high functional impact, very little is known about
      effective strategies for managing cognitive impairment in multiple sclerosis
      (MS). Disease-modifying drugs, such as beta-interferons and glatiramer acetate,
      may prevent or reduce the progression of cognitive dysfunction by containing the
      development of new cerebral lesions. To date, clinical trials have provided
      inconsistent results, with neuropsychological effects documented only in one
      trial. Moreover, pilot studies have tested symptomatic therapies for fatigue, a
      frequent symptom in MS, which may share a common physiopathological substrate
      with cognitive dysfunction. Small trials with amantadine, pemoline, 4
      aminopyridine and 3-4 aminopyridine have provided mainly negative results.
      Acetylcholinesterase inhibitors (AChEI) used to treat Alzheimer's disease (AD)
      such as donepezil, rivastigmine, and galantamine-have recently been tested in
      other cognitive disorders, including MS. The majority of pilot trials with AchEI
      in MS have provided promising results, and the donepezil study recently published
      by Krupp et al. represents a major development in this field. As for non
      pharmacological interventions based on cognitive rehabilitation, few studies have
      used an experimental approach and, in general, results have been disappointingly
      negative. Further research is clearly needed in this area.

PMID- 16643950
TI  - Anti-Hu antibody and refractory nonconvulsive status epilepticus.

PMID- 16643951
TI  - Cognitive impairment and decline in different MS subtypes.
AB  - This paper presents results of two studies conducted to investigate cognition in
      different MS subtypes. First, the results of a study that has previously been
      published will be discussed. This was a cross-sectional study with 108 relapsing
      remitting (RR), 71 secondary progressive (SP), 55 primary progressive (PP) MS
      patients, and 67 healthy controls [S.C.J. Huijbregts, N.F. Kalkers, L.M.J. de
      Sonneville, V. de Groot, I.E.W. Reuling, C.H. Polman, Differences in cognitive
      impairment of relapsing-remitting, secondary and primary progressive MS.
      Neurology 63 (2004) 335-339]. The second study involved a follow-up assessment
      after 2 years and included 30 SPMS patients, 25 PPMS patients, and 33 controls.
      The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used for all
      cognitive assessments. All patient groups demonstrated cognitive deficits
      compared to healthy controls. RRMS patients were less affected compared to
      patients with progressive MS subtypes on the Paced Auditory Serial Addition Task
      (PASAT) and the Symbol Digit Modalities Test (SDMT). These differences were
      attenuated after control for physical disability level as measured by the
      Expanded Disability Status Scale. RRMS and SPMS patients were more severely
      impaired than PPMS patients on the 10/36 Spatial Recall Task and Word List
      Generation. Results of the follow-up study indicated that both progressive MS
      subtypes showed a lack of improvement compared to controls on the PASAT and the
      SDMT, but not on the other tasks of the BRB-N, indicating that performance on
      tasks requiring multiple abilities concurrently, i.e. visuo-spatial ability and
      processing speed (SDMT) or working memory and processing speed (PASAT), is most
      likely to decline across time.

PMID- 16643952
TI  - Mood disorders in multiple sclerosis and the effects on cognition.
AB  - BACKGROUND: Depression and cognitive dysfunction are common in patients with
      multiple sclerosis. However, it is unclear whether depression may cause or
      exacerbate cognitive problems as data remain equivocal. The current review
      attempts to clarify the relationship between these behavioral disorders. METHOD:
      The literature pertaining to the influence of depression on cognition in MS
      patients has been reviewed. RESULTS: Early studies consistently failed to find an
      association and concluded that cognitive dysfunction in MS patients occurred
      independently of depression. A more recent literature has found fault with this,
      citing numerous methodological flaws in the studies undertaken. Newer data now
      suggests that core symptoms of depression reduce cognitive capacity, in
      particular exerting an adverse effect on the executive function component of
      working memory. CONCLUSIONS: Depression may exacerbate cognitive dysfunction in
      MS patients. Whether treating depression will lead to cognitive improvement is
      not yet known, but warrants further exploration.

PMID- 16643953
TI  - Multiple sclerosis-related cognitive changes: a review of cross-sectional and
      longitudinal studies.
AB  - Prevalence estimates of cognitive impairment in multiple sclerosis (MS) range
      from 40% to 65%, depending on the research setting. Cognitive dysfunction
      virtually encompasses all the disease stages and types of clinical course,
      although it is generally less frequent in relapsing-remitting (RR) patients
      compared with secondary progressive (SP) patients, and tends to be less frequent
      in primary progressive (PP) patients. Moreover, it causes role limitations in
      work and social life, independently of the degree of physical disability.
      Relatively little is known about the evolution of cognitive impairment in MS,
      particularly starting from the early stages of the disease. Controlled studies,
      however, have clearly shown that cognitive deterioration tends to progress over
      time. Among clinical predictors, incipient cognitive decline seems to be the
      major risk factor for further deterioration in the short-term. In the long-term,
      the likelihood increases that also patients with initial cognitive preservation
      may deteriorate. As for magnetic resonance imaging (MRI), there are consistent,
      albeit moderate, correlations between the progression of cognitive impairment and
      increasing brain lesion load and brain atrophy. The aim of this paper is to
      provide a review of existing cross-sectional and longitudinal studies on
      cognitive deterioration in MS.

PMID- 16643954
TI  - The adaptive filter of the yeast galactose pathway.
AB  - In the yeast Saccharomyces cerevisiae, the interplay between galactose, Gal3p,
      Gal80p and Gal4p determines the transcriptional status of the genes required for
      galactose utilization. After an increase in galactose concentration, galactose
      molecules bind onto Gal3p. This event leads via Gal80p to the activation of
      Gal4p, which then induces GAL3 and GAL80 gene transcription. Here we propose a
      qualitative dynamical model, whereby these molecular interaction events represent
      the first two stages of a functional feedback loop that closes with the capture
      of activated Gal4p by newly synthesized Gal3p and Gal80p, decreasing
      transcriptional activation and creating again the protein complex that can bind
      incoming galactose molecules. Based on the differential time-scales of faster
      protein interactions versus slower biosynthetic steps, this feedback loop
      functions as a derivative filter where galactose is the input step signal, and
      released Gal4p is the output derivative signal. One advantage of such a
      derivative filter is that GAL genes are expressed in proportion to cellular
      requirements. Furthermore, this filter adaptively protects the cellular receptors
      from saturation by galactose, allowing cells to remain sensitive to variations in
      galactose concentrations rather than to absolute concentrations. Finally, this
      feedback loop, by allowing phosphorylation of some active Gal4p, may be essential
      to initiate the subsequent long-term response.

PMID- 16643955
TI  - Recombinant human thioredoxin suppresses lipopolysaccharide-induced
      bronchoalveolar neutrophil infiltration in rat.
AB  - Human thioredoxin (TRX) is a multifunctional redox-active protein. We previously
      reported that the intraperitoneal administration of recombinant human thioredoxin
      (rhTRX) attenuates inflammatory cytokine- or bleomycin-induced lung injury in
      mice. In this study, the effect of rhTRX injected intravenously after
      lipopolysaccharide (LPS) injection was analyzed in rats. Rats were injected with
      LPS followed by treatment with rhTRX. Although the bolus injection exerted no
      protective effect, continuous intravenous administration of rhTRX significantly
      suppressed percentage number of neutrophils in bronchoalveolar lavage fluid.
      Histological examination also showed that rhTRX decreased neutrophil infiltration
      in the lung tissues. Administered rhTRX was mainly excreted into the urine and
      the tissue accumulation of rhTRX in the lung was marginal. LPS-induced oxidative
      stress in the lung was slight in this model. These results demonstrated that
      continuous intravenous administration of rhTRX suppresses LPS-induced
      bronchoalveolar neutrophil infiltration by an anti-chemotactic effect.
      Administration of rhTRX did not promote the tumor growth nor affect
      chemosensitivity in the xenotransplantation model, suggesting the safety of rhTRX
      therapy for cancer patients.

PMID- 16643956
TI  - Expression of COX-2 and hsp72 in peritoneal macrophages after an acute ochratoxin
      A treatment in mice.
AB  - Ochratoxin A (OTA) is a secondary fungal metabolite produced by Aspergillus and
      Penicillium strains that elicits a broad spectrum of toxicological effects in
      animals and man. A single oral OTA administration (10 mg/kg) in mice induced
      after 24 h oxidative damage and polymorphonuclear leukocyte (PMN) infiltration in
      parenchymal organs. In fact, OTA treatment increased lipid peroxidation (via
      malondialdehyde formation) in kidney and liver and PMN accumulation in duodenum,
      as shown by myeloperoxidase activity. Following in vivo OTA treatment an increase
      of cyclooxygenase-2 and of heat shock protein 72 expression was evidenced in
      peritoneal macrophage lysates by Western blot. That OTA modulates these proteins
      involved in the inflammatory process indicates that the mycotoxin is able to
      activate immune cells. This study suggests that the oxidative stress, the
      neutrophil accumulation in parenchymal tissues and the modulation of inflammatory
      parameters in peritoneal macrophages induced by OTA are involved in its toxicity,
      and represent early events related to several aspects of OTA mycotoxicosis.

PMID- 16643957
TI  - In vitro pharmacological actions of sinomenine on the smooth muscle and the
      endothelial cell activity in rat aorta.
AB  - Vasodilating actions of sinomenine were examined using rat aorta ring strips.
      Sinomenine (0.1 to 100 microM) dilated norepinephrine (NE, 5 microM)-induced
      vasoconstriction in a concentration-dependent manner reaching 68.8+/-5.1% (n=6,
      P<0.01) at a concentration of 100 microM. Sinomenine (100 microM) also attenuated
      KCl (60 mM) and phorbol 12, 13-dibutyrate (PDB, a protein kinase C, PK-C,
      activator, 300 nM)-induced vasoconstriction by 86.9+/-8.5% (n=6, P<0.01) and
      49.9+/-9.8% (n=6, P<0.01), respectively. Pretreatment with nicardipine (a Ca2+
      channel antagonist), staurosporine (a PK-C inhibitor), NG-monomethyl-L-arginine
      acetate (L-NMMA, a nitric oxide, NO, synthesis inhibitor), and indomethacin (a
      cyclooxygenase inhibitor) were carried out. Nicardipine (0.1 microM) led to a
      significant decrease in the vasodilating potential of sinomenine (at 100 microM,
      68.8+/-5.1% vs. 35.5+/-6.9%; n=5, P<0.001). Pretreatment with staurosporine (30
      nM) reduced sinomenine-associated vasodilation from 68.8+/-5.1% to 49.5+/-7.7%
      (n=5, P<0.001), and L-NMMA (100 microM) and indomethacin (10 microM), to 25.3+/
      2.3% (n=5, P<0.001) and to 37.1+/-9.3% (n=5, P<0.001), respectively. The
      responses were almost similar to the results without endothelium. Therefore,
      these results indicate that sinomenine causes the vasorelaxation by the
      mechanisms involved with the inhibitions of Ca2+ channel and PK-C activity, and
      also with the activations of NO and prostaglandin (PG) I2 syntheses in
      endothelium.

PMID- 16643958
TI  - Midkine is a potent regulator of the catecholamine biosynthesis pathway in mouse
      aorta.
AB  - To discover regulatory pathways dependent on midkine (Mk the gene, MK the
      protein) signaling, we compared the transcriptional profiles of aortae obtained
      from Mk -/- and wild type (WT, +/+) mice; the comparison demonstrated an
      extraordinary high level expression of tyrosine hydroxylase (12-fold), the rate
      limiting enzyme in catecholamine biosynthesis, DOPA decarboxylase (73-fold), and
      dopamine beta-hydroxylase (75-fold) in aortae of Mk -/- mice compared with aortae
      of WT (+/+) mice. Phenylethanolamine-N-methyltransferase, the enzyme catalyzing
      the conversion of norepinephrine into epinephrine, was not detected in either Mk 
      /- and WT (+/+) mouse aorta. The protein levels of tyrosine hydroxylase, DOPA
      decarboxylase and dopamine beta-hydroxylase confirmed the analysis of the
      transcriptional profiles. Surprisingly, MK failed to regulate the enzymes of the
      catecholamine biosynthesis pathway in 10 other tissues studied. Furthermore, the
      expression levels of the enzymes of catecholamine biosynthesis in aortae of Mk -/
      mice were effectively the same as those in aortae of Pleiotrophin (Ptn the gene,
      PTN the protein) genetically deficient (Ptn -/-) mice when compared with WT (+/+)
      mice. The remarkable increases in levels of expression of tyrosine hydroxylase,
      DOPA decarboxylase and dopamine beta-hydroxylase suggest that MK together with
      PTN are very important regulators of the catecholamine pathway in mouse aorta and
      may critically regulate catecholamine biosynthesis and function in inflammatory
      and the other pathological conditions in which Mk or Ptn are upregulated. The
      data also establish that norepinephrine is effectively the only catecholamine
      synthesized in mouse aorta.

PMID- 16643959
TI  - Stress-induced breakdown of intestinal barrier function in the rat: reversal by
      wood creosote.
AB  - Our previous studies demonstrated that wood creosote (Seirogan) inhibits
      intestinal secretion and normalizes the transport of electrolytes and water in
      rats subjected to restraint stress. The goal of the present study was to examine
      whether wood creosote has a protective effect against stress-induced breakdown of
      intestinal barrier function. F-344 rats were subjected to 90-min water avoidance
      stress (WAS) with wood creosote (30 mg/kg) or vehicle administered
      intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote
      or vehicle treatment but did not experience the WAS. All rats were euthanized at
      the end of the WAS or sham-stress and the jejunum and colon were isolated.
      Epithelial transport was studied in modified Ussing chambers. Spontaneous
      secretion was assessed by electrophysiological measurement of the short circuit
      current (I(sc)) while electrical conductance (G) was calculated from the
      potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was
      defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS
      significantly elevated basal I(sc) and G and increased epithelial permeability to
      HRP in the jejunum but not in the colon. Wood creosote resulted in a significant
      reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal
      flux of HRP compared to the vehicle-treated group. Wood creosote caused no
      significant effects in sham-stressed rats. The results suggest that oral
      administration of wood creosote may prevent stress-induced diarrhea by preventing
      aversive effects on small intestinal secretion and barrier function.

PMID- 16643960
TI  - Pre-systemic metabolism prevents in vivo antikinetoplastid activity of N1,N4
      substituted 3,5-dinitro sulfanilamide, GB-II-150.
AB  - We previously showed that N1-phenyl-3,5-dinitro-N4,N4-di-n-butylsulfanilamide
      (denoted GB-II-150) possesses selective antimicrotubule activity against
      Leishmania donovani and Trypanosoma brucei in vitro [Bhattacharya, G., Herman,
      J., Delfin, D., Salem, M.M., Barszcz, T., Mollet, M., Riccio, G., Brun, R.,
      Werbovetz, K.A., 2004. Synthesis and antitubulin activity of N(1)- and N(4)
      substituted 3,5-dinitro sulfanilamides against African trypanosomes and
      Leishmania. Journal of Medicinal Chemistry 47, 1823-1832]. When GB-II-150 was
      administered orally to male Sprague-Dawley rats, extensive first-pass metabolism
      of the compound was observed and the oral bioavailability was zero. GB-II-150
      displayed a half-life of 170 min and a clearance of 31.5 mL/min/kg in rats when
      administered intravenously. In vitro metabolism studies indicated that less than
      5% of GB-II-150 remained intact after a 60-min incubation with rat liver S9
      fraction. As expected, the compound was extensively metabolized, with the major
      products resulting from N1-ring oxidation, N4-alkane oxidation, N4-oxidation, and
      nitro reduction. These data indicate that GB-II-150 undergoes rapid and extensive
      first-pass metabolism, precluding the attainment of effective systemic drug
      concentrations and explaining the lack of in vivo antitrypanosomal activity of
      this compound.

PMID- 16643961
TI  - New insights from age determination on toxic element accumulation in striped and
      bottlenose dolphins from Atlantic and Mediterranean waters.
AB  - This study aimed at comparing toxic element (Hg, Cd) bioaccumulation in relation
      to age for bottlenose (Tursiops truncatus) and striped dolphins (Stenella
      coeruleoalba) from Mediterranean and Atlantic waters. Metal concentrations were
      also measured in selected prey to infer metal exposure through the diet. As
      expected, Mediterranean prey exhibited the highest Hg levels, probably as a
      consequence of the Hg enrichment of the Mediterranean Sea. Comparing the
      predators from each area and taking age into account, Mediterranean bottlenose
      dolphins displayed higher Hg levels than Atlantic dolphins (p = 0.032), whereas
      Mediterranean striped dolphins did not (p = 0.691). The consumption of Myctophid
      fish, which showed the highest Hg levels (105+/-80 ngg(-1) w.wt.) among Atlantic
      prey, may explain the high Hg levels in the liver of the Atlantic striped
      dolphins and suggested a preferential offshore feeding behaviour in this area.
      Concerning Cd, no clear differences were found between geographical areas.

PMID- 16643962
TI  - A 3D hydrodynamic fate and transport model for herbicides in Sacca di Goro
      coastal lagoon (Northern Adriatic).
AB  - Sacca di Goro is a shallow coastal microtidal lagoon with a surface area of 26
      km2, and an average depth of about 1.5m. Fresh water pollutant loads from Po
      River branches and several drainage canals lead to anthropogenic eutrophication,
      frequent summer anoxia crises and chemical contamination. Such events not only
      affect the lagoon ecosystem but also cause serious economic losses, the lagoon
      being the second largest producer of clams in Italy. The present work aims at
      using a fate model coupled with COHERENS 3D hydrodynamic model to simulate and to
      explain the spatial distribution and temporal variations of s-triazines
      herbicides in the Sacca di Goro lagoon. The simulation results of spatial and
      temporal dynamic behaviour of atrazine, simazine and terbuthylazine have been
      compared with experimental data obtained during an annual monitoring programme.

PMID- 16643963
TI  - Residue levels of DDTs and toxic evaluation of polychlorinated biphenyls (PCBs)
      in Scyliorhinus canicula liver from the Mediterranean Sea (Italy).

PMID- 16643964
TI  - Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function.
AB  - The previously described Chinese hamster cell mutant V-C8 that is defective in
      Brca2 shows a very complex phenotype, including increased sensitivity towards a
      wide variety of DNA damaging agents, chromosomal instability, abnormal
      centrosomes and impaired formation of Rad51 foci in response to DNA damage. Here,
      we demonstrate that V-C8 cells display biallelic nonsense mutations in Brca2, one
      in exon 15 and the other in exon 16, both resulting in truncated Brca2 proteins.
      We generated several independent mitomycin C (MMC)-resistant clones from V-C8
      cells that had acquired an additional mutation leading to the restoration of the
      open reading frame of one of the Brca2 alleles. In two of these revertants, V-C8
      Rev 1 and V-C8-Rev 6, the reversions lead to the wild-type Brca2 sequence. The V
      C8 revertants did not gain the entire wild-type phenotype and still show a 2.5
      fold increased sensitivity to mitomycin C (MMC), higher levels of spontaneous and
      MMC-induced chromosomal aberrations, as well as abnormal centrosomes when
      compared to wild-type cells. Our results suggest that Brca2 heterozygosity in
      hamster cells primarily gives rise to sensitivity to DNA cross-linking agents,
      especially chromosomal instability, a feature that might also be displayed in
      BRCA2 heterozygous mutation carriers.

PMID- 16643965
TI  - In vitro and in vivo characterization of F-97013-GD, a partial 5-HT1A agonist
      with antipsychotic- and antiparkinsonian-like properties.
AB  - In order to better define the role of 5-HT(1A) receptors in the modulation of
      extrapyramidal motor functions, we investigated the effect of 5-HT(1A) agonists
      on tacrine-induced tremulous jaw movements (TJM) in rats, a putative model of
      parkinsonian tremor. Acute injection of 5-HT(1A) agonists 8-OH-DPAT and buspirone
      dose-dependently counteracted the tacrine-induced oral movements (ED(50)=0.04 and
      1.0mg/kg, respectively), an effect reversed by the selective 5-HT(1A) antagonist
      WAY 100,635. In contrast to classical antipsychotics, the atypical antipsychotics
      risperidone (ED(50)=0.3mg/kg) and clozapine (ED(50)=1.5mg/kg) blocked the oral
      movements induced by the cholinomimetic agent at or below the doses required for
      suppression of conditioned avoidance response. The compound F-97013-GD (6-methyl
      2-[4-(naphtylpiperazin-1-yl)butyl]-3-(2H)-pyridazinone), a putative antipsychotic
      drug that in functional in vitro and in vivo assays behaved as a mixed dopamine
      D(2)-antagonist and 5-HT(1A)-partial agonist, also displayed a potent
      antitremorgenic effect in this paradigm (ED(50)=0.5mg/kg). Interestingly,
      pretreatment with WAY 100,635 blocked the inhibitory effect of F-97013-GD but not
      that of clozapine. The 5-HT depleting agent para-chlorophenylalanine (PCPA)
      partially attenuated tacrine-induced TJM but did not block the suppressive effect
      of 5-HT(1A) agonists. In addition, only high doses of F-97013-GD induced
      catalepsy in rodents and, like 8-OH-DPAT and clozapine, the compound reversed the
      haloperidol-induced catalepsy in rats. These results show that 5-HT(1A) receptors
      play a role in the regulation of tacrine-induced TJM and suggest that their
      activation by novel antipsychotics may not only reduce the extrapyramidal side
      effects EPS liability, but also be effective in the treatment of parkinsonian
      tremor.

PMID- 16643966
TI  - Increased occurrence of left-handedness after severe childhood bacterial
      meningitis: support for the pathological left-handedness hypothesis.
AB  - The hypothesis that brain damage during infancy causes pathological left
      handedness was tested by assessing handedness in 182 survivors of childhood non
      Hemophilus influenza type b bacterial meningitis in the Netherlands (mean age of
      9.7 years). These children were selected randomly after clustering them into
      those with or without parental report on academic and behavioural problems.
      Medical records were obtained from the hospitals, while handedness and
      neurodevelopmental outcome were assessed at school age. Logistic regression
      analysis was used to study the relationship between a severity score of bacterial
      meningitis and handedness. Fifteen percent were left-handed. Severity of
      childhood bacterial meningitis was related to left-handedness (Odds ratio (OR)
      6.2, 95% confidence interval (CI) 2.0-18.6 for those with a total severity score
      above the median as compared to those below). Compared to non-left-handed
      children, left-handed children had lower IQ (mean difference -6.6, 95% CI -12 to 
      1.2), tended to have lower vocabulary scores on WISC-r (-1.0, -2.1 to 0), and
      lower Beery scores on visual-motor integration (-4.9, -10.1 to 0.4). Left-handed
      children also tended to have more combined academic and behavioural limitations
      (OR 2.7, 95% CI 0.9-8.6), lower manual speed of the dominant hand (mean
      difference -9 taps, p < 0.05) and better manual steadiness in the non-dominant
      hand (mean difference of contact's time -2.7 s, p < 0.05). Left-handed post
      meningitic children generally have worse neurodevelopmental outcome than non-left
      handed survivors. Our results support the role of early life brain damage in left
      handedness.

PMID- 16643967
TI  - The contribution of familiarity to associative memory in amnesia.
AB  - In Experiment 1, using the remember/know paradigm with control participants, we
      compared the contribution of recollection and familiarity to associative
      recognition for compound stimuli and for unrelated word pairs. It was
      demonstrated that familiarity makes a greater contribution to associative
      recognition of compound stimuli than to associative recognition of unrelated word
      pairs. In Experiment 2, we examined associative recognition memory in medial
      temporal lobe amnesics, diencephalic amnesics, and control participants for the
      stimuli employed in Experiment 1. Whereas associative recognition for compounds
      and unrelated words was nearly identical in control participants, associative
      recognition was higher for compounds than for unrelated word pairs in amnesic
      patients. This pattern was observed in the medial temporal amnesic group as well
      as in the diencephalic amnesic group. These results suggest that associative
      recognition in amnesia is enhanced to the extent that performance can be
      supported by study-induced familiarity for the studied pair.

PMID- 16643968
TI  - Illusory conjunctions in simultanagnosia: coarse coding of visual feature
      location?
AB  - Simultanagnosia is a disorder characterized by an inability to see more than one
      object at a time. We report a simultanagnosic patient (ED) with bilateral
      posterior infarctions who produced frequent illusory conjunctions on tasks
      involving form and surface features (e.g., a red T) and form alone. ED also
      produced "blend" errors in which features of one familiar perceptual unit
      appeared to migrate to another familiar perceptual unit (e.g., "RO" read as
      "PQ"). ED often misread scrambled letter strings as a familiar word (e.g., "hmoe"
      read as "home"). Finally, ED's success in reporting two letters in an array was
      inversely related to the distance between the letters. These findings are
      consistent with the hypothesis that ED's illusory reflect coarse coding of visual
      feature location that is ameliorated in part by top-down information from object
      and word recognition systems; the findings are also consistent, however, with
      Treisman's Feature Integration Theory. Finally, the data provide additional
      support for the claim that the dorsal parieto-occipital cortex is implicated in
      the binding of visual feature information.

PMID- 16643969
TI  - Theory of mind following traumatic brain injury: the role of emotion recognition
      and executive dysfunction.
AB  - A number of studies have now documented that traumatic brain injury (TBI) is
      associated with deficits in the recognition of basic emotions, the capacity to
      infer mental states of others (theory of mind), as well as executive functioning.
      However, no study to date has investigated the relationship between these three
      constructs in the context of TBI. In the current study TBI participants (N=16)
      were compared with demographically matched healthy controls (N=17). It was found
      that TBI participants' recognition of basic emotions, as well as their capacity
      for mental state attribution, was significantly reduced relative to controls.
      Performance on both of these measures was strongly correlated in the healthy
      control, but not in the TBI sample. In contrast, in the TBI (but not the control)
      sample, theory of mind was substantially correlated with performance on phonemic
      fluency, a measure of executive functioning considered to impose particular
      demands upon cognitive flexibility and self-regulation. These results are
      consistent with other evidence indicating that deficits in some aspects of
      executive functioning may at least partially underlie deficits in social
      cognition following TBI, and thus help explain the prevalence of social
      dysfunction in TBI.

PMID- 16643970
TI  - Salt consumption increases blood pressure and abolishes the light/dark rhythm in
      angiotensin AT1a receptor deficient mice.
AB  - Experiments were performed to study the role of angiotensin (Ang) AT1a receptors
      in dietary sodium-induced changes in blood pressure (BP). We measured light/dark
      rhythms in BP, heart rate (HR) and drinking behavior in Ang AT1a deficient (AT1a 
      /-) and wild type (AT1a +/+) mice with arterial telemetric catheters. Mice were
      given ad libitum access to a high salt diet (8% NaCl, HSD for 8 days) and tap
      water. The major finding was that the Ang AT1a -/- mice showed enhanced sodium
      sensitivity. This was seen by a greater percentage increase in BP (+21% vs. +12%)
      and an earlier onset of BP change (increase on day 5 vs. day 8) in AT1a -/- vs.
      AT1a +/+. The normal light/dark BP rhythm was abolished in AT1a -/- after 5 days
      of HSD. HSD produced an increase in water intake (drinking activity and volume
      consumed) in both groups with no difference in the percentage increase or the
      light/dark drinking rhythm. HSD produced no changes in plasma osmolality,
      hematocrit or body weight in either group. Evidence shows that a deficiency of
      Ang AT1a receptors results in an enhancement in sodium sensitivity along with a
      disruption of the normal light/dark BP rhythm. The data combined with previous
      findings suggests that activation of other components of the renin angiotensin
      system and/or sympathetic pathways may be responsible for the cardiovascular
      changes in AT1a deficient mice.

PMID- 16643971
TI  - Activity and heart rate in semi-domesticated reindeer during adaptation to
      emergency feeding.
AB  - Although reindeer are well adapted to limited food resources during winter, semi
      domesticated reindeer are regularly fed when snow conditions are bad in order to
      prevent starvation. Feeding sometimes results in health problems and loss of
      animals. This study was made to assess if activity pattern in reindeer could be
      used as a tool for the reindeer herder in early detection of animals that are not
      adapting to feeding. The frequency of 10 behavioural categories was recorded in
      five groups of penned, eight-month-old, female semi-domesticated reindeer. Three
      reindeer per group were fitted with heart rate monitors. Lying was the most
      frequent behaviour, whilst there were few cases of agonistic behaviour. Heart
      rate varied during the day, with peaks during feeding and low heart rates in the
      early morning. Restricted feed intake resulted in more locomotion and seeking but
      less ruminating compared to feeding ad libitum. This was followed by a generally
      lower heart rate in reindeer in the restricted groups compared to controls.
      Subsequent feeding with different combinations of lichens, silage and pellets ad
      libitum resulted initially in significantly more of the animals lying curled up,
      compared to controls, combined with increased heart rates. As the experiment
      continued the general activity pattern, as well as the heart rate, gradually
      became more similar in all groups. Lying curled was the behavioural indicator
      most consistently affected by feed deprivation and adaptation to feeding and may
      thus be a useful indicator to distinguish individual reindeer that are not
      adjusting to feeding.

PMID- 16643972
TI  - Gene expression profiling in liver and testis of rats to characterize the
      toxicity of triazole fungicides.
AB  - Four triazole fungicides were studied using toxicogenomic techniques to identify
      potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14
      days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon.
      Following exposure, serum was collected for hormone measurements, and liver and
      testes were collected for histology, enzyme biochemistry, or gene expression
      profiling. Body and testis weights were unaffected, but liver weights were
      significantly increased by all four triazoles, and hepatocytes exhibited
      centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and
      decreased sperm motility, but no treatment-related testis histopathology was
      observed. We hypothesized that gene expression profiles would identify potential
      mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR
      (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal
      cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function
      of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous
      CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as
      well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For
      some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on
      expression, suggesting possible common mechanisms of action. Many of these CYP,
      XME and transporter genes are regulated by xeno-sensing nuclear receptors, and
      hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities
      of toxicogenomic responses in liver between all four triazoles and in testis
      between myclobutanil and triadimefon. Triazoles also affected expression of
      multiple genes involved in steroid hormone metabolism in the two tissues. Thus,
      gene expression profiles helped identify possible toxicological mechanisms of the
      triazole fungicides.

PMID- 16643973
TI  - Differentiation of the roles of NO from airway epithelium and inflammatory cells
      in ozone-induced lung inflammation.
AB  - Mice lacking inducible nitric oxide synthase (NOS2-/-) are more susceptible to
      ozone-induced lung inflammation and injury than their isogenic wild-type
      (NOS2+/+) counterparts, demonstrating an apparent protective effect for NOS2 in
      murine lungs. We hypothesized that nitric oxide (NO) generated from either NOS2
      in the airway epithelial cells or the bone-marrow-derived inflammatory cells was
      responsible for the protective effect of NOS2. To test this hypothesis, we
      prepared chimeric mice by killing their endogenous bone marrow cells by whole
      body irradiation followed by bone marrow transplantation from a heterologous
      donor mouse. We exposed C57BL/6 (NOS2+/+), NOS2-/-, and chimeric NOS2 mice (NOS2
      /+, NOS2+/-) to 1 ppm of ozone for 3 consecutive nights. NOS2-/- mice were more
      severely injured after exposure to ozone than C57BL/6 mice, including a more
      robust inflammatory cell influx (4.14 x 10(5) +/- 2.19 x 10(5) vs. 2.78 x 10(5)
      +/- 1.36 x 10(5) cells respectively; P = 0.036) and greater oxidation of total
      protein sulfhydryls (R-SH) in their blood plasma. Chimeric NOS2-/+ mice, which
      had bone marrow from NOS2-/- mice transplanted into C57BL/6 recipients, had a
      significantly greater response to ozone (increased numbers of neutrophils in lung
      lavage and decreased concentrations of exhaled NO) as compared to the reciprocal
      chimeric strain (NOS2+/-). We conclude that NOS2 has a protective effect against
      acute lung injury caused by ozone inhalation, which may be mediated, in part, by
      NO generated by NOS2 from inflammatory cells, predominantly neutrophils,
      recruited into the lung.

PMID- 16643974
TI  - Correlation between SIV Tat evolution and AIDS progression in cerebrospinal fluid
      of morphine-dependent and control macaques infected with SIV and SHIV.
AB  - Morphine abuse has been associated with higher virus replication and accelerated
      disease progression in a non-human primate model of AIDS. In our previous report,
      we have shown that 50% of morphine-addicted macaques progress rapidly and that
      2/3 of the rapid progressors exhibit severe neuropathogenesis. In this report, we
      examined the sequence evolution of the SIV Tat protein, known to participate in
      AIDS neuropathology, in the cerebrospinal fluid (CSF) of morphine-dependent and
      control macaques over the first 20 weeks of infection. The CSF SIV Tat evolution
      was found to be inversely related with disease progression, and the highly
      neuropathogenic inoculum clone sequence was the prevalent CSF form in rapid
      progressors. Divergence from the inoculum clone was significantly greater in both
      morphine-dependent normal progressors and control macaques than in the morphine
      dependent rapid progressors. Furthermore, we also found evidence of a trend that
      morphine alters the type of mutation, resulting in an enhanced ratio of
      transitions to transversions (Ts:Tv). Rapid disease exacerbates this trend and
      appears to influence the distribution of nonsynonymous changes in the first exon
      of SIV tat, with a clear majority of mutations occurring in the C-terminal half
      of the protein where the known functionally important domains reside. Thus,
      morphine abuse may change the nature and extent of mutations that drive viral
      evolution.

PMID- 16643975
TI  - Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction
      of HIV-1.
AB  - Cyclophilin A (Cyp A) binds the human immunodeficiency virus type 1 (HIV-1)
      capsid (CA) protein and contributes to the early events in virus replication in
      some cells. The retroviral restriction factor TRIM5alpha can inhibit the early,
      post-entry phase of infection by associating with the incoming viral capsid. Cyp
      A has been proposed to prevent restriction factor binding in human cells, thus
      enhancing HIV-1 infectivity, and to potentiate restriction of HIV-1 in monkey
      cells. Here we show that the positive effects of Cyp A-CA binding on HIV-1
      infectivity do not depend on human TRIM5alpha. Disruption of Cyp A binding to CA
      partially relieved the block to HIV-1 infection imposed by several TRIM5alpha
      variants, but Cyp A-CA binding was not absolutely required for TRIM5alpha
      antiviral activity. Inhibition of Cyp A function by cyclosporine significantly
      decreased the efficiency of TRIM5alpha-mediated restriction only when the
      restricted virus capsid interacted with Cyp A.

PMID- 16643976
TI  - Interaction of packaging motor with the polymerase complex of dsRNA
      bacteriophage.
AB  - Many viruses employ molecular motors to package their genomes into preformed
      empty capsids (procapsids). In dsRNA bacteriophages the packaging motor is a
      hexameric ATPase P4, which is an integral part of the multisubunit procapsid.
      Structural and biochemical studies revealed a plausible RNA-translocation
      mechanism for the isolated hexamer. However, little is known about the structure
      and regulation of the hexamer within the procapsid. Here we use hydrogen
      deuterium exchange and mass spectrometry to delineate the interactions of the P4
      hexamer with the bacteriophage phi12 procapsid. P4 associates with the procapsid
      via its C-terminal face. The interactions also stabilize subunit interfaces
      within the hexamer. The conformation of the virus-bound hexamer is more stable
      than the hexamer in solution, which is prone to spontaneous ring openings. We
      propose that the stabilization within the viral capsid increases the packaging
      processivity and confers selectivity during RNA loading.

PMID- 16643977
TI  - Survival of parvovirus B19-infected cells by cellular autophagy.
AB  - Human parvovirus B19 (B19) is a well-known pathogenic agent which causes
      apoptosis in erythrocyte lineage cells. Here, we provide the first evidence that
      mitochondrial autophagy is specifically found in the B19-infected cells. The
      protein expression ratio for LC3-II/LC3-I increased significantly in infected
      cells, indicating possible involvement of cellular autophagy in the infection
      process. Immunofluorescence confocal microscopy analyses revealed that B19
      infection induced an intracellular autophagosome as judged by endogenous LC3
      staining. Moreover, inhibition of autophagy by 3-MA significantly facilitated B19
      infection-mediated cell death. These results suggest a novel mechanism by which
      B19-infected cells survive by cellular autophagy.

PMID- 16643978
TI  - The ltp gene of temperate Streptococcus thermophilus phage TP-J34 confers
      superinfection exclusion to Streptococcus thermophilus and Lactococcus lactis.
AB  - The ltp gene, located within the lysogeny module of temperate Streptococcus
      thermophilus phage TP-J34, has been shown to be expressed in lysogenic strain S.
      thermophilus J34. It codes for a lipoprotein, as demonstrated by inhibition of
      cleavage of the signal sequence by globomycin. Exposure of Ltp on the surface of
      Lactococcus lactis protoplasts bearing a plasmid-encoded copy of ltp has been
      demonstrated by immunogold labeling and electron microscopy. Expression of ltp in
      prophage- and plasmid-cured S. thermophilus J34-6f interfered with TP-J34
      infection. While plating efficiency was reduced by a factor of about 40 and lysis
      of strain J34-6f in liquid medium was delayed considerably, phage adsorption was
      not affected at all. Intracellular accumulation of phage DNA was shown to be
      inhibited by Ltp. This indicates interference of Ltp with infection at the stage
      of triggering DNA release and injection into the cell, indicating a role of Ltp
      in superinfection exclusion. Expression of ltp in L. lactis Bu2-60 showed that
      the same superinfection exclusion mechanism was strongly effective against phage
      P008, a member of the lactococcal 936 phage species: no plaque-formation was
      detectable with even 10(9) phage per ml applied, and lysis in liquid medium did
      not occur. In Lactococcus also, Ltp apparently inhibited phage DNA release and/or
      injection. Ltp appears to be a member of a family of small, secreted proteins
      with a 42 amino acids repeat structure encoded by genes of Gram-positive
      bacteria. Some of these homologous genes are part of the genomes of prophages.

PMID- 16643979
TI  - The temporal and spatial limits of compensation for fixational eye movements.
AB  - High-fidelity eye tracking is combined with a perceptual grouping task to provide
      insight into the likely mechanisms underlying the compensation of retinal image
      motion caused by movement of the eyes. The experiments describe the covert
      detection of minute temporal and spatial offsets incorporated into a test
      stimulus. Analysis of eye motion on individual trials indicates that the temporal
      offset sensitivity is actually due to motion of the eye inducing artificial
      spatial offsets in the briefly presented stimuli. The results have strong
      implications for two popular models of compensation for fixational eye movements,
      namely efference copy and image-based models. If an efference copy model is
      assumed, the results place constraints on the spatial accuracy and source of
      compensation. If an image-based model is assumed then limitations are placed on
      the integration time window over which motion estimates are calculated.

PMID- 16643980
TI  - Electrokinetic enhancement removal of heavy metals from industrial wastewater
      sludge.
AB  - An enhanced electrokinetic process for removal of metals (Cr, Cu, Fe, Ni, Pb, Zn)
      from an industrial wastewater sludge was performed. The electrokinetic
      experiments were conducted under a constant potential gradient (1.25 V cm(-1))
      with processing fluids of tap water (TW), sodium dodecylsulfate (SDS) and citric
      acid (CA) for 5 days. Results showed that metal removal efficiency of heavy
      metals for EK-TW, EK-SDS and EK-CA systems are 11.2-60.0%, 37.2-76.5%, and 43.4
      78.0%, respectively. A highest metal removal performance was found in EK-CA
      system. The removal priority of investigated metals from sludge by EK process was
      found as: Cu > Pb > Ni > Fe > Zn > Cr. The results of sequential extraction
      analysis revealed that the binding forms of heavy metals with sludge after
      electrokinetic process were highly depend upon the processing fluid operated. It
      was found that the binding forms of metals with sludge were changed from the more
      difficult extraction type (residual and sulfate fractions) to easier extraction
      types (exchangeable, sorbed, and organic fraction) after treatment by
      electrokinetic process. Results imply that if a proper treatment technology is
      followed by this EK process to remove metals more effectively, this treated
      sludge will be more beneficial for sludge utilization afterwards. Before it was
      reused, the risk associated with metals of more mobile forms to the environment
      need to be further investigated. The cost analysis was also evaluated for the
      investigated electrokinetic systems.

PMID- 16643981
TI  - Importance of cholinesterase kinetic parameters in environmental monitoring using
      estuarine fish.
AB  - The aim of the present study was to determine the kinetic parameters and
      cholinesterase (ChE) activity in two teleost fish, the white mouth croaker
      Micropogonias furnieri (Scianidae) and the Madamango sea catfish Cathorops spixii
      (Ariidae), to verify their suitability as sentinel species of aquatic pollution
      by anticholinergic compounds. Individuals of each species were captured in one
      reference and one polluted site in the Southern Brazilian coast. Brain tissue was
      used as enzyme source. Inhibition kinetic parameters indicated that ChE from C.
      spixii collected at the reference site showed more affinity (Ka) for eserine that
      from those collected at the polluted site. The opposite was observed for the
      carbamylation constants (Kc). Thus, similar inhibition constants (Ki) were
      observed. M. furnieri brain showed an extremely low sensitivity to in vitro
      inhibition by eserine, indicating that it is not a suitable biomarker to be
      employed in environmental monitoring of anticholinergic compounds. Results from
      the present study also point to the need for considering kinetic analysis when
      cholinesterase activity is employed as a biomarker.

PMID- 16643982
TI  - Impact of sewage sludge spreading on heavy metal speciation in tropical soils
      (Reunion, Indian Ocean).
AB  - This study was designed to evaluate the impact of sewage sludge spreading on
      tropical soilborne heavy metal speciation. Sludgeborne heavy metal speciation was
      also assessed, and the potential mobility of the elements was classified as
      follows: Zn>Ni>>Cu approximately Cr. Two sequential extraction procedures were
      applied to study Cr, Cu, Ni and Zn speciation in control soils and sludge-amended
      soils. We demonstrated that sewage sludge spreading over a 2-year period did not
      have an impact on soilborne heavy metal concentrations but affected speciation of
      the most mobile fractions of Ni and Zn. Both protocols were consistent for the
      organic matter fractions, with an increase in Cu, Zn and Cr concentrations in the
      amended soil as compared to the control soil. In addition, we highlighted that
      the two protocols characterized different pools of organic matter and that
      organic compounds remained in the solid matrix after extraction. With respect to
      the reducible fraction, completely opposite results were obtained with the two
      protocols and the solid residue study revealed that the two schemes were
      ineffective in characterizing iron and manganese fractions.

PMID- 16643983
TI  - Influence of sulfide (S2-) on preservation and speciation of inorganic arsenic in
      drinking water.
AB  - Generally, H2SO4, HNO3, HCl or the combination of ethylenediaminetetraacetate
      with acetic acid (EDTA-HAc) have been used to preserve arsenite and arsenate
      species prior to analysis. When these acidic preservatives are added in sulfidic
      water, instantaneous precipitation of poorly crystalline orpiment, As2S3(am),
      occurs, thereby lowering the total arsenic, As(Tot), analysis. A new method for
      the determination of As(Tot) was developed in which acid-preserved sulfidic water
      samples were oxidized with NaOCl, converting As2S3(am) and thioarsenic species to
      arsenate. A new method was also developed for the separation of uncharged
      arsenite and charged thioarsenic species in fresh, unpreserved sulfidic water by
      adsorbing the charged thioarsenic species while allowing uncharged arsenite to
      pass through a strong-base resin unhindered. The adsorbed thioarsenic species
      could be eluted efficiently with 0.16 M NaOCl solution.

PMID- 16643984
TI  - Dye-sensitized photodegradation of the fungicide carbendazim and related
      benzimidazoles.
AB  - The present work studies the visible-light-promoted photodegradation of the
      colorless fungicide carbendazim (methyl 2-benzimidazolecarbamate) and several 2
      substituted benzimidazoles (SBZ's), in water or water-methanol solution, in the
      presence of air and, as a photosensitizer, the synthetic xanthene dye Rose Bengal
      (RB) or the natural pigment riboflavin (Rf). The results indicate that the
      degradation of each particular SBZ depends on its chemical structure and on the
      sensitizer employed. In the presence of RB, the degradation always operates via a
      singlet molecular oxygen (O(2)((1)Delta(g)))-mediated mechanism, through a highly
      efficient process, as deduced from the comparison of the rate constants for
      physical and chemical quenching of O(2)((1)Delta(g)). In the presence of Rf, the
      visible-light irradiation of any of the studied SBZ's produces a series of
      competitive processes that depend on the relative concentrations of Rf and SBZ.
      These processes include the quenching of excited singlet and triplet Rf states by
      the SBZ and the generation of both O(2)((1)Delta(g)) and superoxide radical anion
      (O(2)(-)), the latter generated by electron transfer from excited Rf species to
      the dissolved oxygen. The overall result is the photodegradation of the SBZ and
      the photoprotection of the sensitizer.

PMID- 16643985
TI  - Pituitary removal in adult mice increases life span.
AB  - Dwarf mutations reduce levels of pituitary hormones and increase life span in
      mice. But because these dwarf mutations confer life-long hormone deficits that
      alter development and dramatically reduce fecundity, the relevance of these
      models to normal aging has been questioned. We examined effects of pituitary
      hormone withdrawal at different ages using hypophysectomy (surgical removal of
      the pituitary). Hypophysectomy at 1 month of age extended life span significantly
      (15%), but hypophysectomy at 9 months of age extended life span to the greatest
      magnitude (21%) of any age we tested. These results demonstrate pituitary hormone
      withdrawal can extend life span even if these hormones are removed relatively
      late in life.

PMID- 16643986
TI  - Migration of fallout radiocaesium in a grassland soil from 1986 to 2001. Part II:
      evaluation of the activity-depth profiles by transport models.
AB  - The vertical migration of (134)Cs, deposited by the Chernobyl fallout (1986), and
      (137)Cs, deposited by the Chernobyl and the global fallout, in the soil of an
      undisturbed Bavarian grassland in Germany was investigated from 1986 to 2001. The
      activity-depth profiles of both isotopes at ten sampling dates were evaluated by
      the classical convection-dispersion equation and a random walk particle model. In
      both models, the apparent migration velocity v and the apparent dispersion
      coefficient D were assumed to be independent of time. However, optimized values
      of v and D were significantly different for the different locations sampled at
      different times. If nevertheless constant values of v and D were used, the
      simulated activity densities per soil layer were out of the range of the spatial
      variability of the observed activity densities determined in 2001. It is
      concluded that without further simultaneous investigations e.g. on bioturbation
      at the study site, migration parameters of radiocaesium determined by classical
      transport models based on convection and dispersion during the first years after
      the deposition of the activity cannot be used for predictive purposes.

PMID- 16643987
TI  - An enzyme-linked immunosorbent assay for rare minnow (Gobiocypris rarus)
      vitellogenin and comparison of vitellogenin responses in rare minnow and
      zebrafish (Danio rerio).
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) was developed to
      determine vitellogenin (Vtg) in rare minnow (Gobiocypris rarus) based on the
      separation and purification of rare minnow Vtg (r-Vtg) as well as the production
      of polyclonal antibody against r-Vtg in rabbits. Three different ELISAs for
      measuring r-Vtg were then compared: (1) indirect ELISA with the antibody against
      carp (Cyprinus carpio) Vtg (c-Vtg) (IC-ELISA); (2) competitive ELISA with the
      antibody against c-Vtg, and using r-Vtg for coating the plates and preparing
      standard curve (CC-ELISA); (3) competitive ELISA with the antibody against r-Vtg,
      and using r-Vtg for coating the plates and preparing standard curve (CR-ELISA).
      The result showed that the homologous CR-ELISA was the most sensitive among the
      three assays for quantifying r-Vtg. The sensitivities to 17alpha-ethinylestradiol
      (EE(2)) of rare minnow and zebrafish (Danio rerio) were compared upon the
      establishment of homologous competitive ELISA. The lowest observed effect
      concentrations (LOECs) to induce Vtg were found to be 0.8 ng EE(2) l(-1) for rare
      minnow and 4 ng EE(2) l(-1) for zebrafish respectively. Afterwards, CR-ELISA was
      applied to measure Vtg concentration in whole body homogenate (WBH) of juvenile
      rare minnow fed by three diets (tubifex from wastewater treatment plant, Artemia
      nauplii and commercial pellet food), and the agreements between bioassay and GC
      MS analysis demonstrated that rare minnow was a sensitive fish model for
      assessing estrogenic effects of endocrine disrupting compounds in aquatic
      environment.

PMID- 16643988
TI  - Water quality and macroinvertebrate community response following pesticide
      applications in a banana plantation, Limon, Costa Rica.
AB  - Pesticides used in banana production may enter watercourses and pose ecological
      risks for aquatic ecosystems. The occurrence and effects of pesticides in a
      stream draining a banana plantation was evaluated using chemical
      characterization, toxicity testing and macrobenthic community composition. All
      nematicides studied were detected in the surface waters of the banana plantation
      during application periods, with peak concentrations following applications.
      Toxicity tests were limited to the carbofuran application and no toxicity was
      observed with the acute tests used. However, since pesticide concentrations were
      generally below the lowest LC50 value for crustaceans but above calculated
      aquatic quality criteria, there remains a risk of chronic toxicity. Accurate
      ecological assessments of pesticide use in banana plantations are currently
      limited by the lack of local short-term chronic toxicity tests and tests using
      sensitive native species. Relatively constant levels of four pesticides
      (imazalil, thiabendazole, chlorpyrifos and propiconazole), which had toxic
      effects according to the 96h hydra and 21d daphnia chronic test, were recorded in
      the effluent of the packing plant throughout the study, indicating that the solid
      waste trap used in this facility was not effective in eliminating toxic
      chemicals. Certain taxa, such as Heterelmis sp. (Elmidae), Heteragrion sp.
      (Megapodagrionidae, Odonata), Caenis sp. (Caenidae, Ephemerotera), and Smicridea
      sp. (Hidropsychidae, Trichoptera), were more abundant at reference sites than in
      the banana farm waters, and may be good candidates for toxicity testing.
      Multivariate analyses of the macroinvertebrate communities clearly showed that
      the banana plantation sites were significantly different from the reference
      sites. Moreover, following the pesticide applications, all the banana plantation
      sites showed significant changes in community composition, with the same genera
      being affected at all sites and for all pesticides (terbufos, cadusafos and
      carbofuran). Consequently, the results presented here show that multivariate
      analysis of community composition was more sensitive in distinguishing pesticide
      effects than the toxicity tests and richness and composition measures used. We
      conclude that monitoring macroinvertebrate communities can be a powerful tool in
      the assessment of ecological effects of banana production.

PMID- 16643989
TI  - Reproductive outcomes of maternal contamination with cyclodiene insecticides,
      hexachlorobenzene and beta-benzene hexachloride.
AB  - The effects of organochlorines on human reproduction have been recently under
      scrutiny. Some negative effects on animal reproduction have been reported. In
      this study we aimed to evaluate the effect of maternal contamination with a
      certain group of organochlorines, which are cyclodienes, HCB (hexachlorobenzene)
      and beta-BHC (beta-hexachlorocyclohexane) on human reproduction. Breast milk
      samples from 815 eligible Victorian mothers were used for measuring maternal
      contamination and the reproductive outcomes such as birth weight, head
      circumference and prematurity were taken from health files. Our study did not
      show any significant negative effect on outcomes such as birth weight, small for
      gestation age, previous miscarriage or still birth, head circumference or sex
      ratio. An inconsistent increase across oxychlordane exposure levels for
      prematurity was found. We also found an inverse association between the highest
      levels of HCB and oxychlordane with previous miscarriage or still birth; but this
      was based on small numbers and may be explained by loss of contaminants through
      the aborted fetus. These results suggest that the declining contamination levels
      of these chemicals do not impose a threat to human reproduction.

PMID- 16643990
TI  - Evaluation of dissipation mechanisms by Lolium perenne L, and Raphanus sativus
      for pentachlorophenol (PCP) in copper co-contaminated soil.
AB  - Though phytoremediation is widely studied in remediation of metal contaminated
      soils or organic contaminated soils, little information is available regarding
      the effectiveness and processes of phytoremediation of sites co-contaminated with
      organic and metal pollutants. Sites co-contaminated with organic and metal
      pollutants are common and considered to be a more complex problem as the two
      components often cause a synergistic effect on cytotoxicity as measured both by
      growth inhibition and colony-forming ability. In this paper, the dissipation
      mechanisms for pentachlorophenol (PCP) in copper co-contaminated soil by Lolium
      perenne L, and Raphanus sativus was investigated in a greenhouse experiment by
      monitoring the growth response of plants, evaluating the removal efficiency of
      extractable PCP, differentiating PCP residuals in strongly and loosely adhering
      rhizosphere soils, and analyzing the microbial activity in the rhizosphere. In
      copper co-contaminated soil with the initial PCP concentration of 50 mg/kg,
      plants grew better with the increment of soil Cu level (0, 150, 300 mg/kg), which
      implied that combinations of inorganic and organic pollutants sometimes exerted
      antagonistic effects on plant cytotoxicity. The observed higher PCP dissipation
      in soil spiked with 50 mg/kg PCP in the presence of Cu and the less difference of
      PCP residual between strongly and loosely adhering soils further suggests the
      occurrence of Cu-PCP interaction and the enhanced degradation and mass flow are
      two possible explanations. In copper co-contaminated soil with the initial PCP
      concentration of 100 mg/kg, however, both plant growth and microbial activity
      were inhibited with the increment of soil Cu level. The lowered degrading
      activity of microorganisms and the reduced mass flow were probably responsible
      for the significantly lower levels of PCP dissipation in copper co-contaminated
      soil. These results showed that remediation of sites co-contaminated with organic
      and metal pollutants is a complex problem and a more thorough understanding of
      the extent and mechanisms by which metals inhibit organic degradation is needed
      to develop phytoremediation of co-contaminated sites.

PMID- 16643991
TI  - How green is my river? A new paradigm of eutrophication in rivers.
AB  - Although the process of eutrophication is reasonably well understood in lakes,
      there is currently no conceptual understanding of how eutrophication develops in
      rivers. This issue is addressed here. A review of the main processes controlling
      the development of eutrophication in lakes has been carried out as a precursor to
      considering the effect in rivers. The importance of hydraulic flushing in
      controlling algal growth suggests that short-retention-time rivers will show
      different effects compared to long retention-time, impounded rivers. The latter
      are likely to operate like lakes, moving from macrophyte domination to
      phytoplankton domination whereas the former move to benthic and filamentous algal
      domination. Subsequently, a conceptual model of the development of eutrophic
      conditions in short-retention-time rivers is developed. Although there is general
      agreement in the literature that an increase in nutrients, particularly
      phosphorus, is a pre-requisite for the eutrophic conditions to develop, there is
      little evidence in short-retention-time rivers that the plant (macro and micro)
      biomass is limited by nutrients and a good case can be made that the interaction
      of hydraulic drag with light limitation is the main controlling factor. The light
      limitation is brought about by the development of epiphytic algal films on the
      macrophyte leaves. The implications of this conceptual model are discussed and a
      series of observable effects are predicted, which should result if the model is
      correct.

PMID- 16643992
TI  - Lipoprotein (a) in patients with spontaneous venous thromboembolism.
AB  - INTRODUCTION: Elevated lipoprotein (a) (Lp (a)) has been established as a risk
      factor of coronary heart disease and stroke. Findings concerning the risk of
      venous thromboembolism (VTE) in adults are contradictory. The aim of our study
      was to investigate, whether elevated Lp (a) levels are an independent risk factor
      of spontaneous symptomatic venous thromboembolism (VTE). Our study was further
      designed to detect differences in risk profiles between thrombosis patients with
      and without symptomatic PE. MATERIALS AND METHODS: We investigated Lp (a) in 128
      patients with spontaneous symptomatic deep vein thrombosis (DVT, group 1), 105
      with spontaneous symptomatic pulmonary embolism with or without DVT (PE, group 2)
      and 122 healthy controls. Lp (a) was measured with an immunoturbidimetric assay
      (Tina-quant(R), Roche, Grenzach-Wyhlen, Germany) on a Hitachi-Modular system.
      RESULTS: Lp (a) levels (mg/L) were not significantly different among groups,
      median levels (25th-75th percentiles) were 170 (51-386) in group 1, 140 (<20-427)
      in group 2 and 126 (54-331) in controls, respectively. As continuous variable,
      odds ratios for VTE for a 100 mg/L increase of Lp (a) were 1.1 [95% confidence
      interval 0.98-1.2] for group 1 versus controls and 1.1 [0.95-1.2] for group 2
      versus controls. The prevalence of Lp (a) above 300 mg/L was not significantly
      different among patients and controls (group 1: 30%, group 2: 32% and controls:
      25%, p=0.4, p=0.2, respectively). CONCLUSIONS: In conclusion we found no
      association between Lp (a) and VTE regardless whether DVT occurred together with
      PE or not.

PMID- 16643993
TI  - Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line
      therapy for patients with suboptimally debulked, advanced epithelial ovarian
      cancer. A phase II trial of sequential doublets. The GO-First Study.
AB  - OBJECTIVES: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer
      with minimal overlapping toxicity. We studied the efficacy and toxicity of this
      combination in patients with advanced ovarian cancer when given prior to
      carboplatin and paclitaxel. METHODS: Chemonaive patients with epithelial ovarian
      cancer and measurable disease were eligible for the study. Treatment consisted of
      gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every
      21 days (GO) for 4 cycles. This was followed by carboplatin AUC = 6 and
      paclitaxel 175 mg/m2 on day 1 every 21 days (CP) for 4 cycles. RESULTS: Twenty
      patients, median age 62 years (range 39-78), FIGO stages III (16) and IV (4)
      received treatment. The response rate (RR) after 4 cycles of GO was 80% (95%CI 61
      99%) (4 complete responses (CR), 12 partial responses (PR)). Interval debulking
      surgery was performed in 7 patients (35%). After CP chemotherapy, RR increased to
      85% (95%CI 68-100%) (CR = 13, PR = 4). Median time to progression was 14.5
      months. Estimated median overall survival was 31.5 months. Toxicities of GO were
      mild; grade 3/4 nausea in 3 patients (15%) and vomiting in 2 patients (10%),
      grade 3/4 neutropenia in 5 patients (25%). Grade 2/3 peripheral neuropathy
      occurred in 5 patients (25%). After sequential administration of CP, grade 2/3
      neuropathy occurred in 13 patients (72%). CONCLUSION: The sequential doublet
      regimen of GO followed by CP resulted in unacceptable neurotoxicity and is not
      recommended for further study; however, the doublet gemcitabine and oxaliplatin
      has significant activity in the first line treatment of patients with ovarian
      cancer.

PMID- 16643994
TI  - Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal
      cancer: a phase II study of the Gynecologic Oncology Group.
AB  - OBJECTIVES: To evaluate the safety and efficacy of cisplatin plus gemcitabine in
      persistent or recurrent platinum-resistant ovarian and primary peritoneal cancer.
      STUDY DESIGN: Eligible, consenting subjects with measurable disease and one prior
      platinum-based regimen, but no prior gemcitabine, were to receive intravenous
      cisplatin followed by gemcitabine on days 1 and 8 every 28 days. RESULTS: Between
      December 2000 and March 2003, 59 patients were enrolled from 24 institutions; two
      were ineligible. During the first stage of accrual, 27 subjects received
      cisplatin 30 mg/m2 and gemcitabine 750 mg/m2. In the second stage, gemcitabine
      was reduced to 600 mg/m2 because of hematologic toxicity at the higher dose.
      There were 4 complete and 5 partial responses for an overall response rate of 16%
      (9/57). Thirty-one women (54%) had stable disease. Median time to progression was
      5.4 months. Overall survival was 14.9+ months. Grade 4 toxicities were
      hematologic, except one cutaneous reaction. CONCLUSIONS: Cisplatin plus
      gemcitabine, in the doses and schedule employed, has modest activity in this
      patient population.

PMID- 16643995
TI  - Uterine leiomyosarcoma with osteoclast like giant cells and long standing
      systemic symptoms.
AB  - INTRODUCTION: The leiomyomatous type of uterine sarcoma with osteoclast-type
      giant cell component is a rare variant of uterine tumors with poor prognosis. The
      histological diagnosis of these rare tumors can be problematic and only five such
      tumors have been published previously. CASE REPORT: A 54-year-old woman presented
      with fever and weight loss for 7 months and laboratory findings suggestive of
      inflammation. After extensive clinical investigation, a uterine tumor was found,
      which was considered to be an incidental finding and was thought to be unlikely
      to explain the symptoms. After hysterectomy, the patient had a surprising and
      quick recovery with the complete relief of systemic symptoms and normalization of
      laboratory changes. The tumor was a dedifferentiated leiomyosarcoma with
      osteoclast-like giant cells and contained extensive necrosis. The patient
      continues to do well and is tumor-free 1 year after the operation. DISCUSSION: To
      our knowledge, this is the first report of a patient being alive and disease-free
      12 months after surgery with a dedifferentiated uterine leiomyosarcoma with
      osteoclast-like giant cells.

PMID- 16643996
TI  - Desmoplastic small round cell tumour: obstetric and gynecological presentations.
AB  - BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare sarcoma
      primarily affecting young men. We report two cases in young women mimicking
      gynaecological malignancy. CASES: A 23-year-old woman underwent caesarean section
      for obstructed labour. At surgery, multiple tumour deposits were found throughout
      abdomen and pelvis. Histology and PCR confirmed DSRCT. Despite chemotherapy, the
      patient relapsed and died 27 months after diagnosis. A 29-year-old woman
      presented with abdominal distension and elevated Ca125. Imaging demonstrated
      widespread tumour within abdomen and pelvis. Histology confirmed DSRCT. Although
      attaining a complete response to chemotherapy, she relapsed within 2 months and
      died 11 months after diagnosis. CONCLUSION: DSRCT should be considered in the
      differential diagnosis of young women presenting with abdominal distension and
      multiple masses on imaging.

PMID- 16643997
TI  - Treatment with 8-OH-DPAT attenuates the weight loss associated with activity
      based anorexia in female rats.
AB  - Serotonin (5-HT) plays an important role in controlling food intake and
      regulating body weight. In addition, clinical studies suggest a possible role for
      5-HT in the etiology of anorexia nervosa. Recently, we have examined the effects
      of pharmacological manipulation of the 5-HT system in female rats exposed to
      conditions that promote activity-based anorexia (ABA). In this animal model of
      anorexia nervosa, rats are food restricted (2 h access/day) while given the
      opportunity to exercise in running wheels. These conditions promote symptoms of
      anorexia nervosa including hypophagia, hyperactivity, progressive weight loss,
      and disruptions of the ovarian reproductive cycle. Previously, we demonstrated
      that increased 5-HT activity increased the weight loss associated with ABA in
      female rats. Here, we investigated whether decreased 5-HT activity would
      attenuate symptoms of ABA. Food-restricted female rats received injections of 8
      OH-DPAT, a drug that reduces serotonergic neurotransmission, or saline vehicle 40
      min prior to food access. During this restricted-feeding phase, food intake was
      similar between groups; however, 8-OH-DPAT prevented the hyperactivity observed
      in saline-treated rats. This resulted in less weight loss in 8-OH-DPAT-treated
      rats, suggesting that decreased activation of the 5-HT system attenuates the
      development of ABA.

PMID- 16643998
TI  - Effects of nicotine withdrawal on performance under a progressive-ratio schedule
      of sucrose pellet delivery in rats.
AB  - Although numerous studies have examined the motivational effects of nicotine
      withdrawal using intracranial self-stimulation (ICSS) threshold assays,
      relatively few have employed other methods for assessing motivation that use
      naturally reinforcing stimuli (e.g., food). The objective of the present study
      was to determine the effects of nicotine withdrawal on motivation using a
      progressive-ratio (PR) schedule of sucrose pellet delivery. Rats were trained to
      respond for sucrose pellets under a PR schedule. When stable breaking points and
      response rates were achieved, PR sessions were suspended and rats were exposed to
      a continuous infusion of saline or nicotine (3.2 or 8.0 mg/kg/day of the base)
      via subcutaneous osmotic minipump for nine days. On day nine, pumps were removed.
      PR sessions resumed 22 h later and continued daily for five consecutive days.
      Only rats exposed to 8.0 mg/kg/day nicotine exhibited a significant decrease in
      breaking point and overall response rate compared to saline-exposed rats on day
      one of nicotine withdrawal. These rats also showed an increasing trend in
      breaking point and overall response rate over the course of withdrawal, such that
      these measures were significantly increased on day five of withdrawal compared to
      baseline. Response rates under each ratio in the PR progression in rats exposed
      to 8.0 mg/kg/day did not differ from baseline or from those in saline-treated
      rats, suggesting suppression of breaking points and overall response rates were
      not attributable to nonspecific motor impairment. In addition, changes in
      performance throughout the protocol were not associated with changes in body
      weight. Consistent with findings from ICSS studies, the present study
      demonstrates that nicotine withdrawal can produce a motivational deficit as
      indexed under a PR schedule. However, in contrast to ICSS, PR performance appears
      to be sensitive to increases in motivation late in the withdrawal period.
      Therefore, PR schedules of natural reinforcement may provide information on the
      motivational effects of nicotine withdrawal complimentary to that obtained from
      ICSS threshold studies.

PMID- 16643999
TI  - Health practices and leukocyte DNA damage in Japanese hard-metal workers.
AB  - OBJECTIVES: To investigate associations between total lifestyles and levels of
      leukocyte DNA damage in healthy Japanese workers. METHODS: Eight health practices
      were investigated in 118 Japanese hard-metal workers by questionnaire in Osaka,
      Japan, in July 2004. Peripheral leukocyte DNA damage levels, as expressed by
      comet parameters, were determined using an alkaline comet assay. RESULTS: After
      crediting one point to each of the health practices and accumulating them into a
      health practice index (HPI: 0-8 points), subjects with poor health practices (HPI
      = 0-3 points) showed a significantly higher tail moment than those with moderate
      (HPI = 4, 5 points) or good health practices (HPI = 6-8 points) (P < 0.01). Risk
      estimates for tail moment above the 75th percentile showed that, compared to
      those with good health practices, subjects with moderate health practices had an
      odds ratio of 1.76 (95% CI: 0.52, 5.91), and those with poor health practices had
      an odds ratio of 6.75 (95% CI: 1.80, 25.27) (P(trend) < 0.01). Multiple
      regression analysis showed that HPI was a significant predictor of the decreased
      tail moment (P < 0.01). CONCLUSION: Poor lifestyles demonstrate a cumulative
      association with leukocyte DNA damage in these Japanese hard-metal workers.

PMID- 16644000
TI  - Validation of the sperm mobility assay in boars and stallions.
AB  - The sperm mobility assay used in the present study measures the rate of sperm
      penetration in a biologically inert cell-separation solution (Accudenz). When a
      sample of sperm is overlaid in a cuvette containing Accudenz, sperm penetrate the
      solution and absorbance of the sample can be measured with a spectrophotometer.
      This assay has been successfully used to select chicken and turkey semen donors.
      We validated this assay for semen from boars and stallions. Absorbance was
      measured after overlaying fresh semen from each species in prefilled cuvettes for
      1, 5, 10, 15, 20, and 40 min. There were no significant differences when sperm
      were incubated in prewarmed cuvettes at 37, 39, or 41 degrees C. However, a
      minimum concentration of 5x10(7) viable sperm/mL was needed to evaluate the rate
      of sperm penetration in boars. Absorbance was half-maximal at 5.4 and 14.1 min
      for boar and stallion sperm, respectively. Frequency analysis suggested a normal
      distribution of mobility values for boar sperm. There were positive correlations
      between mobility values and several computer-aided sperm analysis (CASA)
      parameters. In addition, there was medium repeatability for multiple ejaculates
      from single males. We concluded that the mobility assay can be used for mammalian
      sperm and there seemed to be phenotypic variation among boars in mobility
      estimates.

PMID- 16644001
TI  - Vasectomy effect on canine seminal plasma biochemical components and their
      correlation with seminal parameters.
AB  - Three semen samples were collected at 48 h intervals from 20 mature research dogs
      previously conditioned to manual semen collection. Vasectomy was performed in all
      dogs, and 15 days after surgery, another three ejaculates were similarly
      collected. The semen was evaluated, and centrifuged to obtain seminal plasma for
      measurement of pH, and concentrations of total proteins (TP), total chlorides
      (Cl), calcium (Ca), potassium (K), and sodium (Na). The seminal plasma protein
      profile was evaluated by SDS-PAGE; molecular weights and the integrated optical
      density (IOD) of each band were estimated. There was a negative correlation
      between K concentration and progressive motility (r = -0.49, P = 0.027), sperm
      vigor (r = -0.60, P = 0.0053), and plasma integrity, evaluated by both the hypo
      osmotic swelling test (r = -0.50, P = 0.026) and a fluorescent stain (r = -0.45,
      P = 0.046). Positive correlations between Na and K pre- and post-vasectomy (r =
      0.88, P < 0.001; r = 0.56, P < 0.01, respectively) were verified. There were a
      total of 37 bands pre-vasectomy and 35 post-vasectomy (range, 100.6-3.6 kDa).
      Bands B9 and B13 (42.6 and 29.2 kDa) were not present post-vasectomy. The IOD of
      band B3 (73.5 kDa) was higher (P = 0.03) pre-vasectomy, compared to post
      vasectomy; conversely, the IODs of bands B29 and B37 (7.8 and 3.6 kDa) increased
      (P = 0.026 and 0.047). Pre-vasectomy, there was a positive correlation (r = 0.49,
      P = 0.029) between band B37 band (3.6 kDa) and the Na:K ratio. In conclusion, K
      appeared to be involved in sperm motility in dogs and could be a tool to evaluate
      sperm function. The prostate contributed several elements to canine seminal
      plasma. Vasectomy changed Ca concentrations and the protein profile of the
      seminal plasma. Further studies must be performed to clarify the function of
      these elements on the in vivo fertility of dogs.

PMID- 16644002
TI  - Improved felid embryo development by group culture is maintained with
      heterospecific companions.
AB  - Domestic cat embryos of excellent quality appear to improve development of
      conspecific embryos when cultured together, providing an avenue for improving
      development of embryos from valuable species or individuals. To have relevance to
      rare species, it would be useful to understand if this advantage could be
      conferred by heterospecific companions because there usually are severely limited
      numbers of conspecific embryos available from wildlife donors. In the first
      study, we incubated single test cat embryos alone (controls) or with 10 cat
      embryos or 10 or 20 mouse embryos under similar regimented conditions (each group
      shared 20 microl medium). In the second study, single test cat embryos were
      cultured alone, with 10 conspecific or 20 mouse embryos or 10 cattle embryos
      (each group shared 20 microl medium). Single test embryos in all treatment groups
      achieved similar (P>0.05) stages of compaction and blastocyst development. In the
      first study, only the test embryos incubated with 10 cat or 20 mouse companion
      embryos achieved blastocyst expansion. The average total cell number within test
      embryos incubated with 10 cat or 20 mouse companions was greater (P<0.05) than
      controls or those placed with 10 mouse embryos. In the second study, test embryos
      in all groups achieved blastocyst expansion and had more (P<0.05) total cells per
      embryo than the solitary controls. Inner cell mass to trophoblast cell ratio did
      not differ among treatments in either study. Thus, companion mouse and cattle
      embryos selected for excellent quality confer a benefit to singleton cat embryos,
      although the number of companions necessary to grant an advantage may be species
      dependent. If this phenomenon can be extrapolated across species, this may be an
      avenue for 'common animal embryos' to improve developmental potential of embryos
      from rare, unrelated taxa.

PMID- 16644003
TI  - The impact and potential etiology of teratospermia in the domestic cat and its
      wild relatives.
AB  - Teratospermia (production of >60% morphologically abnormal sperm/ejaculate) is
      relatively common among various species in the family Felidae, which is comprised
      of 37 species. Over two decades of research in this area have produced a
      significant understanding of the phenotypic expression, its impacts on sperm
      function and etiology. There is good evidence suggesting that a reduction in
      genetic diversity contributes to this phenomenon. Results to date demonstrate
      that spermatozoa from teratospermic donors are compromised in the ability to
      undergo capacitation and the acrosome reaction, penetrate the zona-pellucida,
      fertilize conspecific oocytes and survive cryopreservation. Recent studies also
      reveal abnormalities in chromatin integrity in sperm from teratospermic donors,
      which, interestingly, fails to impact fertilization or embryo development after
      intracytoplasmic sperm injection. Through planned inbreeding studies, we now have
      established that teratospermic cats also produce more spermatozoa by virtue of
      more sperm producing tissue, more germ cells per Sertoli cell and reduced germ
      cell loss during spermatogenesis. Overall, it now is clear that gain in sperm
      quantity is achieved at the expense of sperm quality, suggesting an extensive
      disruption of normal testicular function in teratospermic donors. Preliminary
      studies on testicular gene expression in teratospermic cats have also revealed
      abnormal expression patterns. These findings have markedly increased our
      understanding of testis biology in the teratospermic donor and reaffirm the value
      of cats, including wild species, as models for studying novel regulatory
      mechanisms controlling spermatogenesis and spermiogenesis.

PMID- 16644004
TI  - Spatial variations of DMS, DMSP and phytoplankton in the Bay of Bengal during the
      summer monsoon 2001.
AB  - Data on the distribution of dimethylsulphide (DMS) and
      dimethylsulphoniopropionate (DMSP) in relation to phytoplankton abundance in
      different oceanic environments is important to understand the biogeochemistry of
      DMS, which plays an important role in the radiation balance of the earth. During
      the summer monsoon of 2001 measurements were made for DMS and DMSPt (total DMSP)
      together with related biological parameters in the Bay of Bengal. Both DMS and
      DMSPt were restricted to the upper 40 m of the water column. Diatoms accounted
      for more than 95% of the phytoplankton and were the major contributors to the DMS
      and DMSPt pool. The mean concentration of DMS in the upper 40 m was observed to
      be around 1.8+/-1.9 nM in the study area, while DMSPt concentrations varied
      between 0.7 nM and 40.2 nM with a mean of 10.4+/-8.2 nM. The observed lower DMSPt
      in the northern Bay in spite of higher mean primary productivity, chlorophyll a
      and phytoplankton cell counts seemed to result from grazing. Though salinity
      divides the Bay into different biogeochemical provinces there is no relation
      between salinity and DMS or DMSPt. On the other hand DMS was linearly related to
      chlorophyll a:phaeopigments ratio. The results suggest the need for deeper
      insight into the role of diatoms in the biogeochemical cycling of DMS.

PMID- 16644005
TI  - Distribution and sources of surfzone bacteria at Huntington Beach before and
      after disinfection on an ocean outfall-- a frequency-domain analysis.
AB  - Fecal indicator bacteria (FIB) were measured approximately 5 days a week in ankle
      depth water at 19 surfzone stations along Huntington Beach and Newport Beach,
      California, from 1998 to the end of 2003. These sampling periods span the time
      before and after treated sewage effluent, discharged into the coastal ocean from
      the local outfall, was disinfected. Bacterial samples were also taken in the
      vicinity of the outfall during the pre- and post-disinfection periods. Our
      analysis of the results from both data sets suggest that land-based sources,
      rather than the local outfall, were the source of the FIB responsible for the
      frequent closures and postings of local beaches in the summers of 2001 and 2002.
      Because the annual cycle is the dominant frequency in the fecal and total
      coliform data sets at most sampling stations, we infer that sources associated
      with local runoff were responsible for the majority of coliform contamination
      along wide stretches of the beach. The dominant fortnightly cycle in enterococci
      at many surfzone sampling stations suggests that the source for these relatively
      frequent bacteria contamination events in summer is related to the wetting and
      draining of the land due to the large tidal excursions found during spring tides.
      Along the most frequently closed section of the beach at stations 3N-15N, the
      fortnightly cycle is dominant in all FIBs. The strikingly different spatial and
      spectral patterns found in coliform and in enterococci suggest the presence of
      different sources, at least for large sections of beach. The presence of a
      relatively large enterococci fortnightly cycle along the beaches near Newport
      Harbor indicates that contamination sources similar to those found off Huntington
      Beach are present, though not at high enough levels to close the Newport beaches.

PMID- 16644006
TI  - Mussel colonization of a high flow artificial benthic habitat: byssogenesis holds
      the key.
AB  - Water flow is an important characteristic determining the settlement and growth
      of macro-invertebrates in the marine environment. Intake systems of coastal power
      stations offer a unique opportunity to study the effect of water flow on benthic
      organisms under field conditions. The cooling water intake system of a tropical
      coastal power station is used as an experimental facility to study the effect of
      flow on the recruitment and growth of three mussel species, viz, Brachidontes
      variabilis, B. striatulus, and Modiolus philippinarum. The study was prompted by
      earlier observation that these mussels were numerically abundant in the
      biofouling community present inside the seawater intake tunnel of the power
      station, even though their occurrence in the benthic community in the coastal
      waters outside was only nominal. Recruitment data showed that the three mussel
      species very successfully colonised surfaces exposed to the intake mouth
      (characterised by relatively high flow) of the power station. Significant
      difference was observed in the recruitment recorded at the intake point and the
      ambient environment outside. Under high flow condition, the growth rates of all
      the three mussel species were uniformly enhanced. It is argued that recruitment
      of the different species is related to the number of byssus threads produced by
      each mussel and the strength of the byssus threads. The results indicate that
      byssus number and byssus strength of the mussels are important criteria that
      decide successful colonization and establishment in high flow environments.

PMID- 16644007
TI  - Elastic modulus and stress-strain response of human enamel by nano-indentation.
AB  - Nano-indentation with a sharp (Berkovich) and two spherical indenters with
      nominal tip radii of 5 and 20 microm was used to determine the elastic modulus
      and stress-strain response of human enamel. Indentation tests were made over a
      wide range of peak loads from 1 to 450 mN in two orthogonal directions, i.e.,
      parallel and perpendicular to enamel prisms. The elastic modulus and hardness
      (mean contact pressure) versus depth of penetration were determined for the three
      indenters. From the spherical indentation data, stress-strain curves (H-tantheta
      curve) of enamel were determined in the two orthogonal directions and were found
      to be different. The elastic modulus showed load dependence for both orientations
      of the enamel rod structure that depended on the indenter. However, these
      differences could be normalized upon considering the contact diameter. The
      indented sample was imaged with an SEM to investigate the near surface damage. In
      conclusion, prism-sheath structure played an important role in determining the
      mechanical properties as well as the localized fracture of enamel.

PMID- 16644008
TI  - Autoactivation of blood factor XII at hydrophilic and hydrophobic surfaces.
AB  - Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer
      solution is shown not to be specific for anionic hydrophilic procoagulants as
      proposed by the accepted biochemistry of surface activation. Rather, FXII
      activation in the presence of plasma proteins leads to an apparent specificity
      for hydrophilic surfaces that is actually due to a relative diminution of the
      FXII-->FXIIa reaction at hydrophobic surfaces. FXII activation in neat-buffer
      solution was effectively instantaneous upon contact with either hydrophilic
      (fully water-wettable clean glass) or hydrophobic (poorly water-wettable
      silanized glass) procoagulant particles, with greater FXIIa yield obtained by
      activation with hydrophobic procoagulants. In sharp contrast, both activation
      rate and yield was found to be significantly attenuated at hydrophobic surfaces
      in the presence of plasma proteins. Putative FXIIa produced by surface activation
      with both hydrophilic and hydrophobic procoagulants was shown to hydrolyze blood
      factor XI (FXI) to the activated form FXIa (FXIFXIIa-->FXIa) that causes FXI
      deficient plasma to rapidly coagulate.

PMID- 16644009
TI  - Residual anastomoses after fetoscopic laser surgery in twin-to-twin transfusion
      syndrome: frequency, associated risks and outcome.
AB  - Fetoscopic laser coagulation of placental vascular anastomoses is considered to
      be the treatment of choice in severe twin-to-twin transfusion syndrome. The aim
      of fetoscopic laser surgery is to separate completely the inter-twin placental
      circulation. Incomplete laser coagulation may result in residual vascular
      anastomoses. The incidence and clinical implications of residual anastomoses in
      twin-to-twin transfusion syndrome treated with fetoscopic laser surgery has not
      yet been studied. We examined all placentas treated with fetoscopic laser surgery
      and delivered at our center between June 2002 and December 2005 with vascular
      injection using colored dyes. Presence of residual anastomoses was studied in
      association with adverse outcome and inter-twin hemoglobin difference at birth.
      Adverse outcome was defined as fetal demise, neonatal death or severe cerebral
      injury. The relation between residual anastomoses and placental localization
      (anterior or posterior uterine wall) was evaluated. A total of 52 laser-treated
      placentas were studied. Residual anastomoses were detected in 33% (17/52) of
      placentas. Adverse outcome was similar in the groups with and without residual
      anastomoses, 18% (6/34) and 29% (20/70), respectively (p=0.23). Large inter-twin
      hemoglobin differences (>5g/dL) were found in 65% (11/17) of cases with residual
      anastomoses and 20% (7/35) of cases without residual anastomoses (p<0.01).
      Anterior placental localization was not associated with a more frequent presence
      of residual anastomoses. In conclusion, residual anastomoses at our institution
      are seen in one-third of monochorionic placentas treated with fetoscopic laser
      surgery. Although residual anastomoses in our study were not associated with
      adverse outcome, they were often associated with neonatal hematological
      complications.

PMID- 16644010
TI  - CART expression in limbic regions of rat brain following forced swim stress: sex
      differences.
AB  - Our previous studies showed the modulation of cocaine and amphetamine regulated
      transcript (CART) positive neurons and CART mRNA by adrenalectomy and
      corticosterone replacement in hypothalamic nuclei of male rat brain. More
      recently, we have shown by CART immunohistochemistry that restraint and forced
      swim (FS) stress have sexually dimorphic and regionally specific effects on CART
      expression in the hypothalamic nuclei of male and female Sprague-Dawley rats.
      This study aimed to evaluate the effects of FS stress on CART peptide expression
      in hypothalamus, amygdala and hippocampus of male and female (in or near estrus)
      Sprague-Dawley rats. Initially basal CART levels in regions of interest were
      determined in male and female rats; no sex differences were observed. In FS test,
      rats were forced to swim on two consecutive days, in a Plexiglas cylinder for 15
      and 6 min, respectively. Rats were decapitated on the second day, 10 min after
      the stress procedure. Hypothalami, amygdalae and hippocampi were dissected and
      homogenized. CART peptide expression in these regions was measured by Western
      blotting. In males, FS increased CART expression in hypothalamus and amygdala. On
      the other hand, in females, FS lowered CART expression in amygdala. CART
      expression in hippocampus was not affected by the stress procedure in either sex.
      Our results suggest sexually dimorphic modulation of CART expression in
      hypothalamus and amygdala by FS procedure. Although modulation of the CART
      peptide by glucocorticoids and gonadal hormones appears likely, future studies
      are needed to elucidate the underlying mechanisms in the involvement of CART
      peptide in stress response.

PMID- 16644011
TI  - Alternaria aerosol during a bovine respiratory syncytial virus infection alters
      the severity of subsequent re-infection and enhances IgE production.
AB  - BACKGROUND: Previous studies with cattle and rodent models have shown that bovine
      and human RSV infections influence the immune response to inhaled allergen. In
      the present study, we extended these observations to examine the effect of fungal
      allergen Alternaria alternata aerosol exposure (prior to and during BRSV
      infection) on the immune response and clinical outcome of a secondary BRSV
      infection. METHODS: Calves were either Alternaria (Alt)/mock Alt (mAlt) and
      BRSV/mBRSV exposed. Exposures began on day -6 and continued every other day until
      day 6 post infection. A second set of aerosols/infection began on day 103 and
      continued as before. Clinical outcome during infections was measured in each
      group. IgG1, IgA, and IgE responses to Alternaria were measured in serum or
      bronchiolar alveolar lavage fluid (BALF). Cytokine responses, including IL-4,
      were also measured. RESULTS: Alternaria did not influence primary infection;
      however, the Alt/BRSV group had less disease than mAlt/BRSV group (median
      clinical score 8 vs 476.5; p<or=0.01) after secondary infection. Exposure to
      Alternaria facilitated IgE antibody production in BRSV infected calves. IgE
      responses to Alternaria were higher in Alt/BRSV than Alt/mBRSV animals on day 10
      (mean baseline fold increase 1.97 vs 1.06; p=0.013) and 109 (1.40 vs 0.810;
      p=0.008). Comparatively, Alt/BRSV calves had less Alternaria specific IgG1 than
      Alt/mBRSV calves on days 0, 107, 109, 113, 115, and 120 (p<or=0.05) with more
      lung eosinophils and IL-4 secreting PBMCs. CONCLUSION: Alternaria aerosols during
      primary and secondary BRSV infections decreased disease in secondary infections;
      however, BRSV infection enhanced Th2 responses against inhaled Alternaria.

PMID- 16644012
TI  - Autism and environmental genomics.
AB  - Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical
      history and observation but have no biomarkers and are presumably, etiologically
      and biologically heterogeneous. Given brain abnormalities and high monozygotic
      concordance, ASDs have been framed as neurobiologically based and highly genetic,
      which has shaped the research agenda and in particular criteria for choosing
      candidate ASD genes. Genetic studies to date have not uncovered genes of strong
      effect, but a move toward "genetic complexity" at the neurobiological level may
      not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and
      immune), increasing rates and less than 100% monozygotic concordance support a
      more inclusive reframing of autism as a multisystem disorder with genetic
      influence and environmental contributors. We review this evidence and also use a
      bioinformatic approach to explore the possibility that "environmentally
      responsive genes" not specifically associated with the nervous system, but
      potentially associated with systemic changes in autism, have not hitherto
      received sufficient attention in autism genetics investigations. We overlapped
      genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics
      Database, and the SeattleSNPs database of genes relevant to the human immune and
      inflammatory response with linkage regions identified in published autism genome
      scans. We identified 135 genes in overlap regions, of which 56 had never
      previously been studied in relation to autism and 47 had functional SNPs (in
      coding regions). Both our review and the bioinformatics exercise support the
      expansion of criteria for evaluating the relevance of genes to autism risk to
      include genes related to systemic impact and environmental responsiveness. This
      review also suggests the utility of environmental genomic resources in
      highlighting the potential relevance of particular genes within linkage regions.
      Environmental responsiveness and systems impacts consistent with system-wide
      findings in autism are thus supported as important considerations in identifying
      the numerous and complex modes of gene-environment interaction in autism.

PMID- 16644013
TI  - Neurobehavioral function in children with low blood lead concentrations.
AB  - Debate continues as to whether low blood lead level, even below 5 microg/dl,
      impairs neurodevelopmental function in children. This study assessed the
      association between neurodevelopmental performance and lead exposure below 5
      microg/dl in Korean children. Data were collected from 61 children, aged 7-16
      years with a mean blood lead level of 2.9 microg/dl, who participated with their
      mothers. Neurodevelopmental function was measured with computer-based
      neurobehavioral tests. The analyzed data included children's performances on five
      neurobehavioral tests as the dependent variables, and children's blood lead
      level, sex, age, and mother's performance as the four independent variables. For
      simple reaction time and digit span, which, respectively reflect attention and
      short-term memory, there was a small and significant association between the
      children's neurodevelopmental performance and their blood lead levels (p=0.05,
      0.08, respectively). Our study suggests that low blood lead below 5 microg/dl can
      influence children's neurobehavioral performance.

PMID- 16644014
TI  - Application of pharmacokinetic data to the risk assessment of inhaled manganese.
AB  - There is increased interest within the scientific community concerning the
      neurotoxicity of manganese owing in part to the use of methylcyclopentadienyl
      manganese tricarbonyl (MMT) as a gasoline fuel additive and an enhanced awareness
      that this essential metal may play a role in hepatic encephalopathy and other
      neurologic diseases. Neurotoxicity generally arises over a prolonged period of
      time and results when manganese intake exceeds its elimination leading to
      increases in brain manganese concentration. Neurotoxicity can occur following
      high dose oral, inhalation, or parenteral exposure or when hepatobiliary
      clearance of this metal is impaired. Studies completed during the past several
      years have substantially improved our understanding of the health risks posed by
      inhaled manganese by determining exposure conditions that lead to increased
      concentrations of manganese within the central nervous system and other target
      organs. Many of these studies focused on phosphates, sulfates, and oxides of
      manganese since these are formed and emitted following MMT combustion by an
      automobile. These studies have evaluated the role of direct nose-to-brain
      transport of inhaled manganese and have examined differences in manganese
      toxicokinetics in potentially sensitive subpopulations (e.g., fetuses, neonates,
      individuals with compromised hepatic function or sub-optimal manganese intake,
      and the aged). This manuscript reviews the U.S. Environmental Protection Agency's
      current risk assessment for inhaled manganese, summarizes these contemporary
      pharmacokinetic studies, and considers how these data could inform future risk
      assessments of this metal following inhalation.

PMID- 16644015
TI  - Dinuclear zinc(II) complex with novel tripodal polyamine ligand: synthesis,
      structure and kinetic study of carboxy ester hydrolysis.
AB  - An imidazole-containing tripodal polyamine ligand N(1)-(2-aminoethyl)-N(1)-(2
      imidazol-1-ylethyl)-ethane-1,2-diamine (L) was prepared and its dinuclear
      zinc(II) complex [Zn(L)(H(2)O)](2)(ClO(4))(4).4H(2)O (1) was obtained and
      examined as a catalyst for the hydrolysis of 4-nitrophenyl acetate (NA). X-ray
      crystal structure analysis of the complex revealed that the complex features a
      dinuclear cation unit with a Zn...Zn distance of 8.34A and both Zn(II) centers
      adopt distorted trigonal-bipyramid geometry. The solution complexation
      investigation performed at 25 degrees C by means of potentiometric titration
      revealed that the mononuclear species [ZnL](2+) is predominating in the pH rage
      of 7.0-9.7 in the solution and the pK(a1) for the Zn-bound water is 8.50+/-0.01.
      Complex 1 promoted hydrolysis of NA showed a second-order rate constant of
      0.046+/-0.004 M(-1)s(-1) at pH 9.0 in 10% (v/v) CH(3)CN aqueous solution at 25
      degrees C. The pH-rate profile for the second-order rate constant of NA
      hydrolysis with complex 1 gave a sigmoidal curve. And the results show that in
      the hydrolysis process the two Zn(II) centers of the dinuclear deprotonated
      species do not cooperate with each other and the Zn-bound hydroxide servers as
      reactive nucleophile toward the ester.

PMID- 16644016
TI  - B cells in the pathophysiology of autoimmune neurological disorders: a credible
      therapeutic target.
AB  - There is evidence that B cells are involved in the pathophysiology of many
      neurological diseases, either in a causative or contributory role, via production
      of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells
      leading to T cell activation. Clonal expansion of B cells either in situ or
      intrathecally and circulating autoantibodies are critical elements in multiple
      sclerosis (MS), Devic's disease, paraneoplastic central nervous system disorders,
      stiff-person syndrome, myasthenia gravis, autoimmune demyelinating neuropathies
      and dermatomyositis. The pathogenic role of B cells and autoantibodies in central
      and peripheral nervous system disorders, as reviewed here, provides a rationale
      for investigating whether depletion of B cells with new agents can improve
      clinical symptomatology and, potentially, restore immune function. Preliminary
      results from several clinical studies and case reports suggest that B cell
      depletion may become a viable alternative approach to the treatment of autoimmune
      neurological disorders.

PMID- 16644017
TI  - Molecular diversity, trafficking and subcellular localization of GABAB receptors.
AB  - GABAB receptors are the G-protein coupled receptors for the main inhibitory
      neurotransmitter in the brain, gamma-aminobutyric acid (GABA). While native
      studies predicted pharmacologically distinct GABAB receptor subtypes, molecular
      studies failed to identify the expected receptor varieties. Mouse genetic
      experiments therefore addressed whether the cloned receptors can account for the
      classical electrophysiological, biochemical and behavioral GABAB responses or
      whether additional receptors exist. Among G-protein coupled receptors, GABAB
      receptors are unique in that they require 2 distinct subunits for functioning.
      This atypical receptor structure triggered a large body of work that investigated
      the regulation of receptor assembly and trafficking. With the availability of
      molecular tools, substantial progress was also made in the analysis of the
      receptor protein distribution in neuronal compartments. Here, we review recent
      studies that shed light on the molecular diversity, the subcellular distribution
      and the cell surface dynamics of GABAB receptors.

PMID- 16644018
TI  - Proteome analysis to study signal transduction of G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCR) play an important role in drug development.
      Although many classical signal transduction pathways have been elucidated, more
      and more cross-talk to other cascades, e.g. MAP-kinase have been reported. In
      order to identify the overall function of receptor stimulation in a specific cell
      type or under certain conditions proteome analysis has been shown to be a very
      successful and powerful approach. Here, we will summarize the current state of
      the art of proteome analysis applied to GPCR.

PMID- 16644019
TI  - Transplantation of autologous sympathetic neurons as a potential strategy to
      restore metabolic functions of the damaged nigrostriatal dopamine nerve terminals
      in Parkinson's disease.
AB  - Grafting of catecholamine-producing cells can be a possible therapeutic strategy
      for attenuating motor symptoms in Parkinson's disease (PD). The potential of
      autologous sympathetic neurons has been investigated as a donor for cell therapy
      of PD. The clinical trials of autotransplantation of sympathetic ganglion cells
      in PD have revealed that the grafts increase the duration of L-DOPA (L-dihydroxy
      phenyl alanine)-induced beneficial effects, and that the graft-mediated effect is
      detectable during a follow-up period of at least 1 year postgrafting. In an in
      vitro analysis of the ability of human sympathetic neurons to release
      catecholamines, although DA was not detectable under basal conditions, DA levels
      were significantly increased upon exposure to exogenous L-DOPA. Furthermore,
      animal experiments with xenografting of human sympathetic ganglionic neurons in
      the DA-denervated striatum of rats demonstrated that a significant increase in
      striatal DA levels is noted after systemic L-DOPA treatment, and that the DA
      levels remain high for longer periods of time in the grafted rats than in control
      animals with sham surgery. The L-DOPA-induced rise of striatal DA levels was
      significantly attenuated when given reserpine pretreatment. This suggests that DA
      derived from exogenously administered L-DOPA is subjected to, at least in part,
      vesicular storage in grafted sympathetic neurons. Histological examinations
      indeed showed that the grafts express aromatic-L-amino acid decarboxylase and
      vesicular monoamine transporter-2, both of which are important molecules for the
      synthesis and the storage of DA, respectively. Taken together, grafted
      sympathetic neurons can provide a site for both the conversion of exogenous L
      DOPA to DA and the storage of the synthesized DA in the DA-denervated striatum.
      This might be an explanation for a mechanism by which sympathetic neuron
      autografts can increase the duration of L-DOPA effects in PD patients. This
      review article summarizes the clinical effect of transplantation of autologous
      sympathetic neurons in PD and discusses the underlying mechanism for the effect
      based on experimental evidence previously obtained.

PMID- 16644020
TI  - Comparative study of integrating cavity absorption meters.
AB  - Integrating spheres (IS) are widely used for recording spectra of scattering
      samples by placing the specimen inside or outside the sphere. An unusual
      application of integrating spheres has been also demonstrated earlier where the
      liquid sample completely filled the spherical cavity; such a device is often
      called an integrating cavity absorption meter (ICAM). In the present work,
      integrating cavities with different coatings are compared. The spheres were made
      of glass, covered by metal or white paint, and their surfaces were prepared for
      diffuse or specular reflectance. The spheres were evaluated by recording kinetic
      traces following a short light pulse with the aid of time-correlated single
      photon counting (TCSPC), and by recording steady-state spectra through single
      photon counting (SPC) detection. The relative efficiencies of the spheres were
      determined by comparing the steady-state spectra. Possible reasons for
      differences in the performance are discussed.

PMID- 16644021
TI  - Predictive validation study of the Edinburgh Postnatal Depression Scale in the
      first week after delivery and risk analysis for postnatal depression.
AB  - BACKGROUND: Postnatal depression is a major public health problem. The aim of
      this study is to validate the use of the Edinburgh Postnatal Depression Scale
      (EPDS) in the early postpartum, and to identify the markers for risk of postnatal
      depression. METHODS: 815 women filled out an EPDS and general information
      questionnaire between the third and the fifth day postpartum. The women with an
      EPDS score of >8 and a randomized control group from those with scores of <8 were
      contacted 8 weeks postpartum. 363 women therefore had a structured diagnostic
      interview by telephone at 8 weeks postpartum (MINI-DSM-IV), without knowledge of
      their EPDS scores, to screen for a major or minor depressive episode. RESULTS:
      The sensitivity of EPDS was measured as 0.82 [0.78-0.86], with a positivity
      threshold of 9.5/30. For an estimated prevalence for all depressive episodes of
      16.1%, the positive predictive value of EPDS was measured as 42.8% [39.1-46.5%].
      Multivariate risk analysis using logistical regression identified the following
      as risk markers for postnatal depression: previous history of depression
      (postnatal or other), unemployment, premature delivery or stopping breast-feeding
      in the first month for non-medical reasons. CONCLUSION: The use of EPDS between
      the third and fifth day postpartum is valid. An EPDS score of >10 should be
      completed by a clinical assessment and suitable management. The risk markers
      identified here are clinical indices that can be used for first-line early
      screening by non-psychiatric health workers.

PMID- 16644022
TI  - Inhibitors of kB-like gene polymorphisms in rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene
      polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan.
      METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls
      were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing
      was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G,
      and -62 A/T. PCR/restriction fragment length polymorphism was used to determine
      the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421
      was significantly different between DR4(+) RA patients and DR4(+) controls (p =
      0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA
      patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The
      allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+)
      RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4
      147.0). We also found that the allele frequency of IkBL -62 T was significantly
      higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1).
      The allele carriage frequency of IkBL -62 T tended to be increased in RA patients
      (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL
      -421 8T/-62 T tended to be increased in RA patients compared with controls (p =
      0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated
      with the development of RA in Taiwan. The IkBL -421 8T may also be related to
      susceptibility to RA in HLA-DR4(+) individuals. This study shows that the
      estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility
      to RA in Taiwan.

PMID- 16644023
TI  - Immunological studies of mitoxantrone in primary progressive MS.
AB  - Mitoxantrone (MX) has demonstrated efficacy in multiple sclerosis (MS), but its
      immunologic mechanisms of action are poorly understood. Furthermore, no study has
      examined the immunological effects of MX in primary progressive MS (PPMS). This
      study investigated the immunological effects of MX therapy in PPMS patients.
      Lymphocyte phenotypes and chemokine receptor (CCR) expression were evaluated by
      flow cytometry on fresh PBMC from 20 PPMS patients enrolled in a placebo (PLC)
      controlled trial of MX. Longitudinal data were collected at weeks 0, 12, 24, 36
      and short-term data (pre-/post-infusion) were collected at weeks 0 and 36. CXCR3,
      CCR1, CCR2 and CCR5 on CD4 and CD8 T cells and CD14 monocytes were evaluated. MX
      therapy induced a significant increase in the proportion of CD8 T cells (CD45RO(
      )) over 9 months. Expression of several CCR increased following MX treatment. Two
      of the eight MX-treated patients demonstrated dramatic upregulation (70-76%) of
      CCR2 on monocytes. These two patients were the only MX-treated patients to
      demonstrate active inflammation by magnetic resonance imaging (MRI). PLC patients
      did not show significant changes in CCR expression. MX therapy was not associated
      with selective loss of CD4, CD8 or CD14 cells 1 month after treatment or over 9
      months. These results suggest that MX therapy leads to a longitudinal increase in
      CD8 T cells and may increase CCR in patients with inflammation on MRI. Overall,
      MX did not show extensive immune changes in PPMS, although patients with active
      disease (gadolinium enhancing lesions) may identify a subset of PPMS subjects who
      respond immunologically to MX therapy. An improved understanding of MX may help
      identify markers of disease activity and response to therapy.

PMID- 16644024
TI  - Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and
      T cell migration into the spinal cord in experimental autoimmune
      encephalomyelitis.
AB  - Lipoic acid (LA) suppresses and treats murine experimental autoimmune
      encephalomyelitis (EAE), which models multiple sclerosis. However, the mechanisms
      by which LA mediates its effects in EAE are only partially known. In the present
      study, LA (25, 50 and 100 microg/ml) inhibited upregulation of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      tumor necrosis factor-alpha (TNF-alpha) stimulated cultured brain endothelial
      cells. Immunohistochemical analysis of spinal cords from SJL mice that had
      received LA (100 mg/kg/day) following immunization to induce EAE exhibited
      markedly reduced expression of ICAM-1 and VCAM-1 compared with that of EAE mice
      receiving saline. Co-localization analysis showed that ICAM-1 and VCAM-1
      expression increased over endothelial cells (staining positive for von Willebrand
      factor, vWF) in EAE and that LA decreased the expression levels to that observed
      in naive mice. Spinal cords from mice receiving LA had significantly reduced
      inflammation (decreased CD4 and CD11b staining) as compared to EAE mice that
      received saline. Overall, our data suggest that the anti-inflammatory effects of
      LA in EAE may be partly due to inhibition of ICAM-1 and VCAM-1 expression by
      central nervous system (CNS) endothelial cells.

PMID- 16644025
TI  - Improving the sensitivity of single-strand conformation polymorphism (SSCP) to
      study the variability of PLMVd.
AB  - Single-strand conformation polymorphism (SSCP) was used to characterize viroids.
      Eight cDNA clones, which showed identical profiles in preliminary existing SSCP
      analysis but had different sequences, were chosen to develop a sensitive SSCP
      technique for identifying the variability of Peach latent mosaic viroid (PLMVd).
      Polyacrylamide Gel Electrophoresis (PAGE) conditions were optimized to improve
      the sensitivity of the existing SSCP, and a modified SSCP protocol was developed.
      The results indicated that the modified SSCP protocol provided an overall
      sensitivity in identifying the variability of these clones, and showed higher
      resolution than the existing one and its improved versions. As shown by sequence
      analyses of cDNA clones of PLMVd and the modified SSCP profiles, there is no
      close correlation between the number of base changes and variation of the
      modified SSCP band patterns. The potential use of the modified SSCP analysis is
      discussed as a tool for viroids characterization.

PMID- 16644026
TI  - Development and validation of a direct homologous quantitative sandwich ELISA for
      fathead minnow (Pimephales promelas) vitellogenin.
AB  - Vitellogenin (Vtg) is an established and sensitive endpoint for analysis of
      exposure to (anti-)oestrogens and their mimics in fish [Sumpter, J.P., 1995.
      Feminized responses in fish to environmental estrogens. Toxicol. Lett. 82, 737
      742; Arukwe, A., Goksoyr, A., 2003. Eggshell and egg yolk proteins in fish:
      hepatic proteins for the next generation: oogenetic, population, and evolutionary
      implications of endocrine disruption. Comp. Hepatol. 2, 4. ]. In some instances,
      links have been drawn between high level induction of Vtg and adverse health
      effects in fish [Herman, R.L., Kincaide, H.L., 1988. Pathological effects of
      orally administered estradiol to rainbow trout. Aquaculture 72, 165-172;
      Schwaiger, J., Spieser, O.H., Bauer, C., Ferling, H., Mallow, U., Kalbfus, W.,
      Negele, R.D., 2000. Chronic toxicity of nonylphenol and ethinyloestraiol:
      haematological and histopathological effects in juvenile common carp (Cyprinus
      carpio). Aquat. Toxicol. 51, 69-78]. The widespread use of Vtg as a biomarker has
      led to the development of a variety of assays to quantitatively measure Vtg
      concentrations in tissue samples from fish, and hence a need for a
      standardization of the performance criteria and validation of such assays
      [Goksoyr, A., Eidem, J.K., Kristiansen, S.I., Nilsen, B.M., 2003. On the need for
      a standardized set-up for validation studies of fish vitellogenin assays as an
      endpoint in endocrine disruptor testing and screening-a proposal. ]. One of the
      most popular test fish species for assessing chemical effects is the fathead
      minnow (Pimephales promelas), which is now used widely for studies into endocrine
      disruption [Panter, G.H., Hutchinson, T.H., Lange, R., Lye, C.M., Sumpter, J.P.,
      Zerulla, M., Tyler, C.R., 2002. Utility of a juvenile fathead minnow screening
      assay for detecting (anti)estrogenic substances. Environ. Toxicol. Chem. 21, 319
      326; Hutchinson, T.H., Yokota, H., Hagino, S., Ozato, K., 2003. Development of
      fish tests for endocrine disruptors. Pure Appl. Chem. 75, 2343-2353]. This paper
      describes the development and validation of a new, homologous enzyme-linked
      immunosorbent assay (ELISA) for quantification of Vtg in this fish species.

PMID- 16644027
TI  - Assessing the occurrence of a stress syndrome in mussels (Mytilus edulis) using a
      combined biomarker/gene expression approach.
AB  - A combination of biomarkers and gene expression analyses was used to investigate
      the occurrence of a stress syndrome in mussels (Mytilus edulis) caged along a
      copper pollution gradient in the Visnes fjord, Norway. The stress level in
      mussels, as calculated by a novel algorithm (the "Expert System") from a set of
      seven biomarkers, was compared with gene expression changes utilising a low
      density oligonucleotide microarray, employing 24 different genes involved in both
      cellular homeostasis and stress-related responses. The biomarker battery included
      lysosomal membrane stability, lysosomal accumulation of neutral lipids and
      lipofuscin, lysosomal/cytoplasm volume ratio, Ca(2+)-ATPase and catalase
      activities, and total metallothionein content. Integration of the biomarkers into
      the Expert System ranked individuals sampled at site 2 as unstressed, mussels
      sampled at site 3 as being subject to low stress, and those from site 4, which is
      adjacent to what used to be a copper mine, as being highly stressed, with respect
      to specimens sampled from the reference site. Microarray analyses demonstrated
      that at the two innermost and mostly polluted sites, gene expression patterns
      where severely altered. In particular, some genes exhibited a linear activation
      response along the copper gradient, e.g. metallothioneins mt 20 and mt 10, and
      catalase. In addition, stress responsive kinase (krs), glutathione transferase
      (gst), major vault protein and histones (h1, h2a and h4) were significantly up
      regulated at the innermost site. In conclusion, these results demonstrated that
      sites could be discriminated using both a physiological and a molecular approach.
      The development of a stress syndrome along the pollution gradient was evidenced
      with a novel mussel microarray, both in terms of numbers of regulated genes and
      level of gene response.

PMID- 16644028
TI  - Heterologous expression of proteins from Plasmodium falciparum: results from 1000
      genes.
AB  - As part of a structural genomics initiative, 1000 open reading frames from
      Plasmodium falciparum, the causative agent of the most deadly form of malaria,
      were tested in an E. coli protein expression system. Three hundred and thirty
      seven of these targets were observed to express, although typically the protein
      was insoluble. Sixty-three of the targets provided soluble protein in yields
      ranging from 0.9 to 406.6 mg from one liter of rich media. Higher molecular
      weight, greater protein disorder (segmental analysis, SEG), more basic
      isoelectric point (pI), and a lack of homology to E. coli proteins were all
      highly and independently correlated with difficulties in expression.
      Surprisingly, codon usage and the percentage of adenosines and thymidines (%AT)
      did not appear to play a significant role. Of those proteins which expressed,
      high pI and a hypothetical annotation were both strongly and independently
      correlated with insolubility. The overwhelmingly important role of pI in both
      expression and solubility appears to be a surprising and fundamental issue in the
      heterologous expression of P. falciparum proteins in E. coli. Twelve targets
      which did not express in E. coli from the native gene sequence were codon
      optimized through whole gene synthesis, resulting in the (insoluble) expression
      of three of these proteins. Seventeen targets which were expressed insolubly in
      E. coli were moved into a baculovirus/Sf-21 system, resulting in the soluble
      expression of one protein at a high level and six others at a low level. A
      variety of factors conspire to make the heterologous expression of P. falciparum
      proteins challenging, and these observations lay the groundwork for a rational
      approach to prioritizing and, ultimately, eliminating these impediments.

PMID- 16644029
TI  - Bifunctional role of the leishmanial antimonate reductase LmACR2 as a protein
      tyrosine phosphatase.
AB  - LmACR2 is the first identified antimonate reductase responsible for the reduction
      of pentavalent antimony in pentostam to the active trivalent form of the drug in
      Leishmania. LmACR2 is a homologue of the yeast arsenate reductase Acr2p and Cdc25
      phosphatases and has the HC[X]5R phosphatase motif. Purified LmACR2 exhibited
      phosphatase activity in vitro and was able to dephosphorylate a phosphotyrosine
      residue from a synthetic peptide. This phosphatase activity was inhibited by
      classical inhibitors such as orthovanadate. LmACR2-catalyzed phosphatase activity
      was inhibited by either antimonate or arsenate. Site-directed mutagenesis
      experiments showed that the H74C[X]5R81 motif was involved in catalysis. This is
      the first report of a metalloid reductase with a bifunctional role in protein
      tyrosine phosphatase activity. Leishmania is never exposed to metalloids during
      its life cycle. It is therefore unlikely that it would evolve an enzyme
      exclusively for drug activation. We propose that the physiological function of
      LmACR2 is to dephosphorylate phosphotyrosine residues in leishmanial proteins.

PMID- 16644030
TI  - Histone mediated gene activation in Toxoplasma gondii.
AB  - DNA processes, including transcriptional activation, are largely governed by
      histone modifications. For most eukaryotes, chromatin-remodeling machines have
      been identified that move, replace, or decorate histones. Recent studies have
      shed some important light on similar machinery operating in apicomplexan
      parasites, including the opportunistic pathogen Toxoplasma gondii. Here we
      present a synthesis of the current knowledge of histone mediated gene expression
      in Toxoplasma, particularly in the context of parasite differentiation.

PMID- 16644031
TI  - Translational initiation in Leishmania tarentolae and Phytomonas serpens
      (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5' sequence
      context.
AB  - To investigate the influence of sequence context of translation initiation codon
      on translation efficiency in Kinetoplastida, we constructed a library of
      expression plasmids randomized in the three nucleotides prefacing ATG of a
      reporter gene encoding enhanced green fluorescent protein (EGFP). All 64 possible
      combinations of pre-ATG triplets were individually stably integrated into the
      rDNA locus of Leishmania tarentolae and the resulting cell lines were assessed
      for EGFP expression. The expression levels were quantified directly by measuring
      the fluorescence of EGFP protein in living cells and confirmed by Western
      blotting. We observed a strong influence of the pre-ATG triplet on the level of
      protein expression over a 20-fold range. To understand the degree of evolutionary
      conservation of the observed effect, we transformed Phytomonas serpens, a
      trypanosomatid parasite of plants, with a subset of the constructs. The pattern
      of translational efficiency mediated by individual pre-ATG triplets in this
      species was similar to that observed in L. tarentolae. However, the pattern of
      translational efficiency of two other proteins (red fluorescent protein and
      tetracycline repressor) containing selected pre-ATG triplets did not correlate
      with either EGFP or each other. Thus, we conclude that a conserved mechanism of
      translation initiation site selection exists in kinetoplastids that is strongly
      influenced not only by the pre-ATG sequences but also by the coding region of the
      gene.

PMID- 16644032
TI  - Ghrelin response to protein and carbohydrate meals in relation to food intake and
      glycerol levels in obese subjects.
AB  - Obese subjects have lower basal and an attenuated decrease of postprandial plasma
      ghrelin following carbohydrate-rich meals, while the response to protein is
      unknown. Therefore, plasma ghrelin levels were examined after ingestion of
      satiating amounts of a protein- or carbohydrate-rich meal in relation to food and
      energy intake and hunger/satiety ratings in 30 obese subjects followed 240 min
      later by ad lib sandwiches. Food intake and hunger/satiety ratings were identical
      while energy intake was significantly greater after bread (861 +/- 62.7 vs. 441
      +/- 50.4 kcal, p < 0.001). Second meal food and energy intake were not different.
      Ghrelin decreased after bread, but increased by 50 pg/ml (p < 0.001) after meat.
      The corresponding increase of insulin was 55 vs. 9 microU/ml (p < 0.001).
      Glycerol levels decreased significantly less after the protein meal compared to
      carbohydrates. After protein glycerol was significantly correlated to the rise of
      ghrelin but not insulin. These data demonstrate that, in obese subjects, protein
      has no different satiating effect than carbohydrate despite divergent ghrelin
      levels. Energy intake corresponds to energy density of the respective food items.
      Ghrelin response to both meals is qualitatively similar but quantitatively
      attenuated compared to normal weight subjects. The relationship between ghrelin
      and glycerol would support recent observations of a possible role of ghrelin in
      fat metabolism.

PMID- 16644033
TI  - Glucose regulates expression of the nerve growth factor (NGF) receptors TrkA and
      p75NTR in rat islets and INS-1E beta-cells.
AB  - BACKGROUND: The function and survival of pancreatic beta-cells strongly depend on
      glucose concentration and on autocrine secretion of peptide growth factors. NGF
      and its specific receptors TrkA and p75NTR play a pivotal role in islet survival
      and glucose-dependent insulin secretion. We therefore investigated whether or not
      glucose concentration influences expression of TrkA and p75NTR in rat islets and
      in INS-1E beta-cells at the mRNA and protein level (INS-1E). METHODS: Gene
      expression of the NGF receptors TrkA and p75NTR but also of the metabolic gene
      liver-type pyruvate kinase (L-PK) and the neurotrophin receptors TrkB and TrkC
      was studied by semi-quantitative PCR and by real-time PCR in islets and INS-1E
      beta-cells. RESULTS: In rat islets, high glucose exposure (25 mmol/l) increased
      gene expression of TrkA, p75NTR and L-PK. Expression of TrkA, p75NTR and L-PK
      reflected insulin secretion at the respective glucose concentration. In rat INS
      1E insulinoma cells, expression of L-PK and p75NTR was suppressed by low glucose
      as in the islets, while expression of TrkA was strongly increased by low glucose
      levels and thus was regulated differently than in islets. Expression of TrkB and
      TrkC was not regulated by glucose concentration at all. TrkA protein was
      regulated in the same fashion as its mRNA expression, while p75NTR protein was
      not significantly regulated within 24 h. CONCLUSION: Glucose interacts with gene
      expression of TrkA and p75NTR that are strongly involved in beta-cell growth and
      glucose-dependent insulin secretion. The fact that TrkA expression is regulated
      the opposite way in islets and in INS-1E beta-cells might reflect their specific
      grade of differentiation and tendency to proliferate.

PMID- 16644034
TI  - Corticosteroids induce the differential expression of TGFbeta isoforms, receptors
      and signaling in the gastric mucosa of suckling rats.
AB  - Glucocorticoids inhibit the cell proliferation in the gastric epithelium, and
      induce differentiation, migration and death. The mechanism by which these effects
      are triggered and controlled is still discussed and can involve the transcription
      and activation of transforming growth factor beta (TGFbeta). The present study
      was conducted to evaluate the effect of hydrocortisone short-term treatment on
      tissue level and distribution of TGFbeta isoforms, receptors and signaling
      through Smad2/3. To achieve that, 18-day-old rats were injected with
      hydrocortisone (50 mg/Kg b.wt.) for 0, 1 and 3 h. The stomachs were collected and
      processed for immunohistochemistry and western blotting. We observed that the
      treatment for 3 h increased the number of labeled epithelial cells for TGFbeta1
      (p < 0.05), decreased the distribution of TGFbeta2 (p < 0.05) and did not alter
      TGFbeta3, TbetaRI and TbetaRII status. The levels of TGFbeta1 and receptors were
      checked by western blotting and results corroborate the immunodetection. We also
      found that phosphorylation of Smad2/3 into Smad2P increased after 3 h (p < 0.05),
      indicating that the high level TGFbeta1 was active on the cells. We suggest that
      glucocorticoids differentially regulate the expression of TGFbeta isoforms,
      receptors and signaling, and so TGFbeta1 might be involved in the inhibitory
      pathway triggered by the hormone.

PMID- 16644035
TI  - Isoproterenol stimulates monocyte chemoattractant protein-1 expression and
      secretion in 3T3-L1 adipocytes.
AB  - Recently, monocyte chemoattractant protein (MCP)-1 has been characterized as a
      novel adipocytokine upregulated in obesity and insulin resistance which impairs
      insulin signaling in muscle and fat in vitro. Growing evidence, on the other
      hand, suggests that increased activity of the sympathetic nervous system is an
      integral part in the development of insulin resistance. In the current study, the
      impact of the beta-adrenergic agonist isoproterenol on MCP-1 mRNA synthesis and
      secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol
      increased MCP-1 secretion 3-fold. Furthermore, 10 microM isoproterenol acutely
      induced MCP-1 mRNA by up to 5.3-fold in a time-dependent fashion with significant
      stimulation seen at concentrations as low as 0.3 microM effector. Studies using
      pharmacological inhibitors suggested that basal and isoproterenol-induced MCP-1
      expressions are mediated via beta-adrenergic receptors and protein kinase A.
      Moreover, acute activation of adenylyl cyclase by forskolin was sufficient to
      mimic the effects of isoproterenol. Taken together, our results demonstrate that
      isoproterenol induces MCP-1 expression and secretion via a classical GS-protein
      coupled pathway and support the notion that MCP-1 might be an interesting novel
      candidate linking obesity and insulin resistance.

PMID- 16644036
TI  - DC cardioversion of persistent atrial fibrillation: a comparison of two
      protocols.
AB  - BACKGROUND: Current guidelines for transthoracic direct-current cardioversion
      (DCCV) of atrial fibrillation (AF) recommend a step-up energy protocol. The aim
      of this study was to compare such a protocol with a protocol involving a high
      initial energy shock, anteroposterior paddle position and reversal of shock
      polarity, on cardioversion efficacy, total energy delivery, use of sedation and
      patient tolerability. METHODS: 261 patients (mean age 71+/-10 years, 62% male)
      referred for elective DCCV of persistent AF were enrolled. Patients were
      randomised to either protocol A: (1) 200 J anteroapical, (2) 360 J anteroapical,
      (3) 360 J anteroposterior; or protocol B: (1) 360 J anteroapical, (2) 360 J
      anteroposterior, and (3) 360 J posteroanterior. All procedures were performed
      under sedation with intravenous diazepam. RESULTS: Protocol B improved shock
      success rates (protocol A first shock success rate=42%, protocol B=68%, p<0.001;
      protocol A second shock success rate=72%, protocol B 86%, p=0.006; protocol A
      third shock success rate=83%, protocol B=92%, p=0.03) and required fewer shocks
      to achieve sinus rhythm (1.3+/-0.6) compared with protocol A (1.6+/-0.7,
      p<0.001). There were no differences in cumulative energy used (protocol A 473+/
      286 J, protocol B 436+/-273 J, p=0.24) or sedation requirements (protocol A
      diazepam 22.1+/-9.0 mg, protocol B 21.7+/-8.9 mg, p=0.75). Both protocols were
      equally well tolerated by patients. CONCLUSION: High initial energy increased
      success rates and decreased the number of shocks but resulted in similar
      cumulative energy delivery, sedation use and patient tolerability compared with a
      conventional step-up protocol.

PMID- 16644037
TI  - Ankle-arm index as a predictor of lesion morphology and risk classification for
      coronary artery disease undergoing angioplasty.
AB  - BACKGROUND: Low ankle-arm systolic blood pressure index is strongly correlated
      with various cardiovascular risk factors. However, although the potential hazards
      of resulting coronary artery disease (CAD) are well established, no data is
      available regarding how ankle-arm index (AAI) and CAD severity are related.
      METHODS: This study enrolled 477 patients and all patients underwent coronary
      angiography and AAI measurements. Based on AAI values, patients were divided into
      study (AAI value of <0.9, 126 patients) and control groups (AAI value of >or=0.9,
      351 patients). RESULTS: Among baseline characteristics, the study group showed a
      significantly older and higher female ratio than the control group. The presence
      of hypertension, diabetes mellitus (DM), current smoking status and LDL
      cholesterol level differed significantly between these two groups. Mean number of
      lesions and target vessel involvement were significant different between the
      study and control group (2.6+/-1.1 vs. 1.9+/-1.0, p<0.0001; 2.0+/-0.8 vs. 1.6+/
      0.7, p<0.0001). Percentages of lesion sites on ostial and proximal portions were
      markedly high in the study group than in the control group. Significant
      differences also emerged in the complex stenotic lesions (B2 or C) and lesion
      morphology (calcified, chronic total occlusion, irregular, bifurcation and
      diffuse) of these two groups. Multivariate logistic regression analysis, showed
      that AAI is a statistically significant independent predictor for lesion site,
      complex stenotic lesions and lesion morphology with Odds ratios (ORs) of,
      respectively, 1.728, 2.880 and 2.71. CONCLUSIONS: The AAI is a useful non
      invasive tool for the prediction of CAD severity.

PMID- 16644038
TI  - Regional ventricular dynamics during acute coronary occlusion: a comparison of
      invasive with non-invasive echocardiographic markers to detect and quantify
      myocardial ischaemia-observations made during off-pump coronary surgery.
AB  - OBJECTIVES: To investigate the performance of non-invasive markers used in stress
      echocardiography to detect the presence and depth of myocardial ischaemia. We
      therefore sought to compare these non-invasive markers during acute coronary
      occlusion in humans. METHODS: 27 patients with stable angina and normal LV cavity
      size were studied during off-pump coronary artery bypass grafting to the left
      anterior descending coronary artery using transoesophageal echocardiography and
      simultaneous high fidelity LV pressure. Regional power development of the
      anterior wall was plotted throughout the cardiac cycle, allowing the measurement
      of its time course, peak value and time integral (intrinsic work). Regional
      effective myocardial work was calculated and its reduction during acute occlusion
      was used as the invasive standard for ischaemic dysfunction. RESULTS: In all
      patients acute coronary occlusion led to a delay in the onset of regional wall
      thickening which persisted after aortic valve closure. These time intervals of
      myocardial thickening had the highest qualitative concordance with the gold
      standard of a fall in effective work. Regression models identified three
      significant predictors of the depth of myocardial ischaemia; the interval from Q
      wave to the onset of regional thickening, duration of post-ejection thickening
      and peak thickening rate. Objective wall thickening and thinning rates were not
      significant predictors. CONCLUSIONS: The regional timing of myocardial thickening
      and peak thickening rate accurately predicted the presence and indicated the
      depth of local ischaemia during acute coronary occlusion. These markers may
      complement subjective wall motion scores aimed at predicting the presence of
      epicardial coronary artery disease. CONDENSED ABSTRACT: We compared non-invasive
      markers commonly used in stress echocardiography using measurements of the fall
      in regional myocardial work with coronary occlusion as a standard. 27 patients
      were studied using transoesophageal echocardiography and simultaneous high
      fidelity left ventricular pressure during off-pump coronary surgery. Delayed
      myocardial thickening had the highest qualitative concordance with the gold
      standard of a fall in effective work, while regression models identified three
      significant predictors; the interval Q wave to the onset of regional thickening,
      duration of post-ejection thickening and peak thickening rate. These markers may
      complement current non-invasive indices of ischaemia during clinical stress
      testing.

PMID- 16644039
TI  - Ductus-associated proximal pulmonary artery stenosis in patients with right heart
      obstruction.
AB  - Proximal pulmonary artery stenosis is a common acquired lesion in infants treated
      for congenital heart disease. We hypothesized that a large number of stenoses
      develop at the site of ductal insertion in patients with right ventricular
      outflow tract obstruction (RVOTO) and that these patients are at risk for
      developing hypoplasia of the ipsilateral pulmonary artery. The surgical and
      cardiac catheterization databases at our institution during the years 1988-2000
      were searched for all patients under 1 year of age carrying a diagnosis of
      pulmonary atresia with intact ventricular septum (PA), tetralogy of Fallot (TOF)
      or pulmonary stenosis (PS), yielding 700 patients (62 PA, 373 TOF, 265 PS). The
      cardiac catheterization database was also searched for all patients with any
      diagnosis under 1 year of age found at catheterization to have proximal pulmonary
      artery stenosis. Proximal pulmonary artery stenosis associated with the ductal
      insertion site was diagnosed at catheterization in 33 infants (18 with PA, 5 with
      TOF, 6 with PS, 4 other diagnoses). This represents 29% of patients with PA, 1%
      with TOF and 2% with PS. Among patients with RVOTO and ductal insertion site
      associated stenosis, there was a high prevalence (59%) of associated distal
      pulmonary arterial hypoplasia, defined as diameter of the stenosed vessel at
      first distal branch < or = 80% the diameter of the contralateral vessel.
      Symptomatology failed to identify this lesion; therefore, a high index of
      suspicion is necessary if proximal pulmonary artery stenosis is to be detected
      early in these patients.

PMID- 16644040
TI  - Blood rheological properties are strongly related to the metabolic syndrome in
      middle-aged Chinese.
AB  - The current investigation sought to evaluate the relation between hemorheological
      properties and the metabolic syndrome. 1400 office workers aged 35 to 59 years
      were enrolled in this study. Waist circumference and blood pressure were
      determined. Plasma high-density lipoprotein (HDL cholesterol), triglyceride,
      fasting blood glucose, plasma insulin and whole blood viscosity (WBV) at a high
      shear rate of 200 s(-1) were measured at the attendance. Metabolic syndrome was
      defined according to National Cholesterol Education Program (NCEP)/ATP III
      guidelines. The metabolic syndrome was identified in 18% of this sedentary
      population. Mean WBV was 4.71+/-0.56 mPa s. One-way ANOVA indicated WBV increased
      across subjects with 0-4 metabolic syndrome components (F=3.86, p<0.01). The
      highest vs. lowest quartiles of WBV occurred significantly more often among
      subjects as the number of metabolic syndrome components increased. Across five
      categories of the metabolic syndrome, the frequencies of the occurrence of the
      highest vs. lowest quartiles were: 0.40, 0.87, 1.31, 1.92, and 4.80,
      respectively, showing a significant correlation (R=0.817, p<0.05). Univariate
      logistic regression analysis showed that the prevalence of hyperviscosity was
      predicted positively by waist circumference (OR=1.018, 95% CI: 1.002-1.035,
      p<0.05) and negatively by HDL cholesterol (OR=0.295, 95% CI: 0.133-0.680,
      p<0.01), independently of age, sex, and smoking status. In summary, this study
      has shown that WBV is strongly related to the severity of the metabolic syndrome.
      We suggest that the hemorheological parameters could potentially be used as an
      additional indicator of the metabolic syndrome.

PMID- 16644041
TI  - Tru9 I restriction polymorphism in vitamin D receptor may cause failure of PCR
      amplification in Bsm I polymorphism.

PMID- 16644042
TI  - B-type natriuretic peptide and assessment of jeopardised myocardium in acute
      myocardial infarction.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is used as prognostic marker in
      acute coronary syndromes. It is unknown whether BNP reflects the amount of
      jeopardised myocardium in the initial phase of acute ST-elevation myocardial
      infarction (STEMI). METHODS: Patients admitted for percutaneous coronary
      intervention in the acute phase of STEMI were studied. Samples for BNP were taken
      at the time of coronary intervention and were correlated with the amount of
      jeopardised myocardium. This was defined on coronary angiography as the vascular
      region distal to the infarct-related lesion and was expressed by a vascular
      score. The extend of epicardial injury on ECG was evaluated by: summation of ST
      segment elevation in the infarct-related leads, number of leads with > or = 1 mm
      ST-segment elevation and number of leads with > or = 1 mm ST-segment
      depression/elevation. RESULTS: A total of 113 patients (median age (25th, 75th
      percentile) 61 (54, 69)) were studied. Median BNP was 27 pg/ml (12, 62) and was
      assessed 225 min (150, 315) after onset of pain. There was no significant
      relation between BNP and vascular score (r=0.026, p=0.8). The only independent
      variable of BNP was time delay between onset of pain and sample collection.
      Stepwise regression identified the extent of ST-segment elevation as independent
      predictor of the vascular score. CONCLUSION: At initial presentation of STEMI,
      BNP measurement does not allow a correct prediction of jeopardised myocardium. In
      contrast, ST-segment analysis, in particularly the extent of ST-segment
      elevation, provides useful information about the extent of jeopardised
      myocardium.

PMID- 16644043
TI  - Contractile effects of angiotensin and endothelin in failing and non-failing
      human hearts.
AB  - BACKGROUND: Angiotensin II (Ang II) and endothelin-1 (ET-1) share their effects
      on growth of myocardial cells but have been shown to elicit different effects on
      myocardial function. However, these effects vary markedly among species, cardiac
      regions (atrium or ventricle) and failing or non-failing myocardium. We therefore
      investigated the effects of both peptides on contractile function of isolated
      human myocytes from failing and non-failing hearts. METHODS AND RESULTS:
      Cardiomyocytes were enzymatically isolated and electrically stimulated (15 V, 0.2
      Hz). Ang II elicited a positive inotropic effect (PIE) mediated by activation of
      protein kinase C (PKC) in atrial but no effect in ventricular myocytes. ET-1 (10(
      8) M) increased cell-shortening by 146+/-9.3% (p<0.05) in atrial myocytes, by
      99.1+/-16.5% (p<0.05) in non-failing ventricular but only by 40.5+/-6.4% (p<0.05)
      in failing ventricular myocytes. The PIE of ET-1 in failing myocytes was more
      pronounced at low extracellular pH (+112.6+/-27% at pH 7.0 vs. +40.5+/-6.4% at pH
      7.4, p<0.05). Amiloride, a sodium-hydrogen-exchange inhibitor, inhibited two
      thirds of the PIE of ET-1 in failing myocytes. The PKC-inhibitor decreased the
      PIE by 50% from 113% to 64% in ventricular myocytes under acidotic conditions.
      CONCLUSION: Ang II and ET-1 elicited PIE in atrial myocytes, whereas in
      ventricular myocytes Ang II did not induce PIE in contrast to ET-1. The PIE of ET
      1 was markedly attenuated in failing myocytes. Under acidotic conditions, the PIE
      of ET-1 was more pronounced in failing myocytes, indicating that ET-1 may
      activate signaling processes in failing myocytes, which are not activated in
      normal myocytes.

PMID- 16644044
TI  - Analyses of dose-response in radiotherapy for patients with mature T/NK-cell
      lymphomas according to the WHO classification.
AB  - BACKGROUND AND PURPOSE: This study was conducted to analyze the influence of
      radiotherapy doses and chemotherapy doses and clinical parameters on in-field
      disease control in order to assess the optimal radiation doses for treatment of
      mature T/NK-cell lymphomas according to the newly proposed WHO classification.
      PATIENTS AND METHODS: Subjects consisted of 62 patients with mature T/NK-cell
      lymphomas treated with radiotherapy at four Japanese institutions between 1983
      and 2002. We reevaluated all histopathological specimens of non-Hodgkin's
      lymphomas (NHL), using the WHO classification. Radiation therapy was usually
      delivered to the involved field. The majority of patients also received
      adriamycin-based chemotherapy such as CHOP, modified CHOP, or more intensive
      chemotherapy. RESULTS: There were no significant differences in radiosensitivity
      among subtypes of mature T/NK-cell lymphomas, at least between extranodal NK/T
      cell lymphomas, nasal type and peripheral T-cell lymphomas, unspecified. There
      was a radiation dose-response in non-bulky mature T/NK-cell lymphomas, indicating
      that radiation doses of more than 52 Gy may be required to obtain in-field
      control. However, it was difficult to obtain local control of bulky T-cell
      lymphomas, even with high doses of irradiation. CONCLUSIONS: Mature T/NK-cell
      lymphomas were more radioresistant than B-cell lymphomas such as diffuse large B
      cell lymphomas (DLBCL). The chemotherapy including adriamycin did not improve the
      in-field control of mature T/NK-cell lymphomas. These results were obtained by
      using non-randomized data and the significance of these results is limited by
      bias in data. However, our results suggest that the treatment strategy which is
      usually used for DLBCL, that is, a combined modality of CHOP and around 40 Gy of
      radiotherapy, may not be sufficiently effective for mature T/NK-cell lymphomas.

PMID- 16644045
TI  - Effects of visual stimulation on cortico-spinal coherence during isometric hand
      contraction in humans.
AB  - The effects of visual stimuli on cortico-spinal synchronization were investigated
      by measuring the coherence between electroencephalogram (EEG) and electromyogram
      (EMG) during isometric contraction of the first dorsal interosseous muscle of the
      right hand. Because a spinal motoneuron and the corresponding muscle fibers form
      a motor unit with one-to-one correspondence of their action potentials, the EMG
      indirectly measures the activity of the corresponding spinal neuronal group. The
      tasks were isometric contraction (Control condition); and isometric contraction
      with concurrent ignoring of visual stimuli (VS condition). By comparing the
      Control and VS conditions, the following results were obtained. The coherence
      increased significantly in magnitude, but was unchanged in frequency range (beta
      band) and scalp location; the EEG and EMG spectral power in the beta band were
      unchanged in amplitude; and the alpha and gamma bands of EEG spectral power were
      significantly increased and decreased, respectively. These findings suggest that
      the cortico-muscular coherence reflects the cognitive effort needed to maintain
      isometric muscle contraction. When visual stimuli need to be ignored, the
      cognitive effort and cortico-spinal coherence are enhanced.

PMID- 16644046
TI  - Neuroscience is awaiting for a breakthrough: an essay bridging the concepts of
      Descartes, Einstein, Heisenberg, Hebb and Hayek with the explanatory formulations
      in this special issue.
AB  - The paper presents gedankenmodels which, based on the theories and models in the
      present special issue, describe the conditions for a breakthrough in brain
      sciences and neuroscience. The new model is based on contemporary findings which
      show that the brain and its cognitive processes show super-synchronization.
      Accordingly, understanding the brain/body-mind complex is possible only when
      these three are considered as a wholistic entity and not as discrete structures
      or functions. Such a breakthrough and the related perspectives to the brain/body
      mind complex will involve a transition from the mechanistic Cartesian system to a
      nebulous Cartesian system, one that is basically characterized by parallel
      computing and is further parallel to quantum mechanics. This integrated outlook
      on the brain/body-mind, or dynamic functionality, will make the treatment of also
      the meta-cognitive processes and the greater part of the iceberg, the
      unconscious, possible. All this will be possible only through the adoption of a
      multidisciplinary approach that will bring together the knowledge and the
      technology of the four P's which consist of physics, physiology, psychology and
      philosophy. The genetic approach to the functional dynamics of the brain/body
      mind, where the oscillatory responses were found to be laws of brain activity, is
      presented in this volume as one of the most recent perspectives of neuroscience.

PMID- 16644047
TI  - Heterogeneity of posterior limbic perfusion in very early Alzheimer's disease.
AB  - PURPOSE: This study was designed to quantify the heterogeneity of cerebral
      perfusion on SPECT images in elderly controls and Alzheimer's disease (AD)
      patients in mild stage using a three-dimensional fractal analysis (3D-FA).
      MATERIAL AND METHOD: Seventy-five patients with possible and probable AD based on
      the NINCDS/ADRDA criteria, and thirty-one elderly controls underwent 99mTc-HMPAO
      SPECT scanning. Dementia severity was assessed using the clinical dementia rating
      (CDR). Patients with CDR scores of 0.5 (n=33) were classified as "very early" and
      those with CDR 1 (n=42) as "early". We delineated the SPECT images using 2
      cutoffs (35% and 50% cutoffs of the maximal voxel radioactivity) and measured the
      number of voxels in the areas included by the contours obtained with each cutoff
      level. The fractal dimension (FD) was calculated by relating the logarithms of
      cutoff level and the number of voxels. Posterior limbic images were reconstructed
      at 30 degrees positive to the coronal plane, and posterior limbic FD was
      calculated. RESULT: Posterior limbic FD for early AD, very early AD, and control
      groups were 1.03+/-0.16, 1.02+/-0.17, and 0.87+/-0.14 (P=0.001 versus early AD
      group, P=0.001 versus very early AD). Use of the posterior limbic FD and the
      ratio of posterior limbic FD to total FD separated very early AD patients from
      controls with a sensitivity of 76% and a specificity of 81%. CONCLUSION: 3D-FA
      indicated significant differences in the heterogeneity of CBF distribution
      between patients with AD in mild stage and elderly controls. Posterior limbic FD
      may be useful for easily and objectively distinguishing patients with very early
      AD from aging people.

PMID- 16644048
TI  - Identification and functional significance of polymorphisms in the mu-opioid
      receptor gene (Oprm) promoter of C57BL/6 and DBA/2 mice.
AB  - C57BL/6J and DBA/2J mice demonstrate differences in morphine preference when
      tested in a two-bottle choice paradigm. Quantitative trait loci (QTL) mapping
      suggested the proximal region of chromosome 10 was responsible for 41% of the
      observed genetic variance. The mu-opioid receptor (MOR) gene (Oprm) maps to this
      region and is a prime candidate for explaining the QTL. We hypothesized that
      variations in Oprm between these strains are responsible for differences in
      morphine preference. We identify five single nucleotide polymorphisms (SNPs) in
      the Oprm promoter; three within or near putative transcription factor binding
      sites. Promoter fragments were amplified from genomic DNA by polymerase chain
      reaction (PCR) and subcloned into luciferase reporter vectors. A significant
      difference in basal Oprm promoter activity was seen with C57BL/6 and DBA/2
      approximately 1675 constructs in MOR-positive BE(2)-C cells, but not in MOR
      negative Neuro-2a cells. In BE(2)-C cells, average DBA/2 approximately 1675
      construct activity was 1.3-2.0x greater than average C57BL/6 activity suggesting
      that the SNPs might alter MOR expression in these two mouse strains. Significant
      differences in promoter activities between the two cell lines suggest that cell
      type-specific transcription factors are involved. No significant differences in
      construct activity were found between untreated and morphine-treated BE(2)-C or
      Neuro-2a cells, suggesting that morphine does not regulate transcription of Oprm.

PMID- 16644049
TI  - Chemically surface modified gel (CSMG): an excellent enzyme-immobilization matrix
      for industrial processes.
AB  - Invertase from S. cerevisiae has been immobilized on porous silica matrix, formed
      using sol-gel chemistry, with surface area of approximately 650 m(2)/g. The co
      condensation of silica sol with 3-aminopropyl(triethoxy)silane produced an amino
      chemically surface modified silica gel (N-CSMG) with a very high ligand loading
      of 3.6 mmol/g SiO(2); significantly higher than commercially available matrices.
      Surface amine groups were activated with glutaraldehyde to produce GA-N-CSMG, and
      invertase covalently attached by the aldehyde. Invertase was used as a model
      enzyme to measure the immobilizing character of the GA-N-CSMG material. Using an
      optimized immobilization protocol, a very high loading of 723 mg invertase per
      gram GA-N-CSMG is obtained; 3-200-fold higher than values published in
      literature. The reproducible, immobilized activity of 246,000 U/g GA-N-CSMG is
      also greater than any other in literature. Immobilized invertase showed almost
      99% retention of free enzyme activity and no loss in catalytic efficiency. The
      apparent kinetic parameters K(M) and V(M) were determined using the Michealis
      Menten kinetic model. K(M) of the free invertase was 1.5 times greater than that
      of the immobilized invertase--indicating a higher substrate affinity of the
      immobilized invertase. These findings show considerable promise for this material
      as an immobilization matrix in industrial processes.

PMID- 16644050
TI  - Engineering increased thermostability in the thermostable GH-11 xylanase from
      Thermobacillus xylanilyticus.
AB  - Enzymatic hydrolysis constitutes an attractive strategy for biorefining of
      abundant, low-cost agricultural by-products such as wheat bran and straw.
      However, to adopt such an approach, efficient enzymes are required, in particular
      xylanases. To promote heat-induced disorganization of the complex cell wall
      network in wheat bran and thus increase enzymatic hydrolysis, we have attempted
      to improve the thermoresistance of a GH-11 xylanase that is already moderately
      thermostable. Using a previously described engineering strategy that involves the
      introduction of disulphide bridges, a mutant (Tx-xyl-SS3) displaying enhanced
      thermostability and thermoactivity was obtained. The half life at 70 degrees C
      (180 min) of Tx-xyl-SS3 is 10-fold greater than that of the wild type enzyme and
      its specific activity is almost doubled (3500 IU mg(-1)). Despite these
      improvements, Tx-xyl-SS3 was unsuitable for use at significantly higher reaction
      temperatures (i.e. 85-95 degrees C) and thus the initial objective of this study
      remained unaccomplished. However, unexpectedly even at the normal hydrolytic
      temperature (60 degrees C), Tx-xyl-SS3 was able to solubilize 50% of the wheat
      bran arabinoxylans, 10 points more than the wild type enzyme in parallel
      reactions. The data presented here show that this improvement is not directly
      linked to the increase in thermostability and/or thermoactivity, but rather to
      other unidentified changes to physico-chemical properties that may allow Tx-xyl
      SS3 to better penetrate the cell wall network in wheat bran.

PMID- 16644051
TI  - The effect of polysaccharide-degrading wine yeast transformants on the efficiency
      of wine processing and wine flavour.
AB  - Commercial polysaccharase preparations are applied to winemaking to improve wine
      processing and quality. Expression of polysaccharase-encoding genes in
      Saccharomyces cerevisiae allows for the recombinant strains to degrade
      polysaccharides that traditional commercial yeast strains cannot. In this study,
      we constructed recombinant wine yeast strains that were able to degrade the
      problem-causing grape polysaccharides, glucan and xylan, by separately
      integrating the Trichoderma reesei XYN2 xylanase gene construct and the
      Butyrivibrio fibrisolvens END1 glucanase gene cassette into the genome of the
      commercial wine yeast strain S. cerevisiae VIN13. These genes were also combined
      in S. cerevisiae VIN13 under the control of different promoters. The strains that
      were constructed were compared under winemaking conditions with each other and
      with a recombinant wine yeast strain expressing the endo-beta-1,4-glucanase gene
      cassette (END1) from B. fibrisolvens and the endo-beta-1,4-xylanase gene cassette
      (XYN4) from Aspergillus niger, a recombinant strain expressing the pectate lyase
      gene cassette (PEL5) from Erwinia chrysanthemi and the polygalacturonase-encoding
      gene cassette (PEH1) from Erwinia carotovora. Wine was made with the recombinant
      strains using different grape cultivars. Fermentations with the recombinant VIN13
      strains resulted in significant increases in free-flow wine when Ruby Cabernet
      must was fermented. After 6 months of bottle ageing significant differences in
      colour intensity and colour stability could be detected in Pinot Noir and Ruby
      Cabernet wines fermented with different recombinant strains. After this period
      the volatile composition of Muscat d'Alexandria, Ruby Cabernet and Pinot Noir
      wines fermented with different recombinant strains also showed significant
      differences. The Pinot Noir wines were also sensorial evaluated and the tasting
      panel preferred the wines fermented with the recombinant strains.

PMID- 16644052
TI  - Tobamovirus infection is independent of HSP101 mRNA induction and protein
      expression.
AB  - Heat shock protein 101 (HSP101) has been implicated in tobamovirus infections by
      virtue of its ability to enhance translation of mRNAs possessing the 5'Omega
      leader of Tobacco mosaic virus (TMV). Enhanced translation is mediated by HSP101
      binding to a CAA-repeat motif in TMV Omega leader. CAA repeat sequences are
      present in the 5' leaders of other tobamoviruses including Oilseed rape mosaic
      virus (ORMV), which infects Arabidopsis thaliana. HSP101 is one of eight HSP100
      gene family members encoded by the A. thaliana genome, and of these, HSP101 and
      HSP98.7 are predicted to encode proteins localized to the cytoplasm where they
      could potentially interact with TMV RNA. Analysis of the expression of the
      HSP100s showed that only HSP101 mRNA transcripts were induced significantly by
      ORMV in A. thaliana. The induction of HSP101 mRNA was also correlated with an
      increase in its protein levels and was independent of defense-related signaling
      pathways involving salicylic acid, jasmonic acid, or ethylene. A. thaliana
      mutants lacking HSP101, HSP98.7, or both supported wild-type levels of ORMV
      replication and movement. Similar results were obtained for TMV infection in
      Nicotiana benthamiana plants silenced for HSP101, demonstrating that HSP101 is
      not necessary for efficient tobamovirus infection.

PMID- 16644053
TI  - Sequence analysis of coat protein gene of Wuhan nodavirus isolated from insect.
AB  - Wuhan nodavirus (WhNV) particles are isometric, non-enveloped, and about 29 nm in
      diameter. In the previous study, we determine its physiochemical characterization
      and the nucleotide sequence of the larger genomic segment, RNA1 and identify it a
      nodavirus. WhNV RNA1 is 3,149 nt in length, encoding protein A, catalytic subunit
      of RNA-dependent RNA polymerase (RdRp). In this report, we complete the sequence
      determination of the smaller genomic segment, RNA2 of WhNV. WhNV RNA2 is
      determined to be 1,562 nt long, containing a 430-amino-acid open reading frame
      (ORF) encoding the coat protein of WhNV with a calculated molecular mass of
      47,856 Da. The homology of the coat protein of WhNV and the homologous proteins
      of other nodaviruses either alphanodaviruses or betanodaviruses is very low. WhNV
      coat protein shares the highest identity (24%) with that of Lates calcarifer
      encephalitis virus (LCEV), a betanodavirus, and shares less than 16% identical
      amino acids with each of the alphanodaviruses. Furthermore, the prediction of
      WhNV capsid structure by 3D-PSSM shows that the capsid structure of WhNV
      resembles that of tomato bushy stunt virus (TBSV), a tombusvirus, which contains
      two domains, rather than the expected single-domain capsid protein of insect
      nodaviruses. The phylogenetic analysis indicates that WhNV is the most distantly
      related of both the alphanodaviruses and betanodaviruses, which provides
      significant new data for understanding the evolution of the nodavirus family.

PMID- 16644054
TI  - Sustained release of nanosized complexes of polyethylenimine and anti-TGF-beta 2
      oligonucleotide improves the outcome of glaucoma surgery.
AB  - The purpose of this study was to design microspheres combining sustained delivery
      and enhanced intracellular penetration for ocular administration of antisense
      oligonucleotides. Nanosized complexes of antisense TGF-beta2 phosphorothioate
      oligonucleotides (PS-ODN) with polyethylenimine (PEI), and naked PS-ODN were
      encapsulated into poly(lactide-co-glycolide) microspheres prepared by the double
      emulsion solvent evaporation method. The PS-ODN was introduced either naked or
      complexed in the inner aqueous phase of the first emulsion. We observed a marked
      influence of microsphere composition on porosity, size distribution and PS-ODN
      encapsulation efficiency. Mainly, the presence of PEI induced the formation of
      large pores observed onto microsphere surface. Introduction of NaCl in the outer
      aqueous phase increased the encapsulation efficiency and reduced microsphere
      porosity. In vitro release kinetic of PS-ODN was also investigated. Clearly, the
      higher the porosity, the faster was the release and the higher was the burst
      effect. Using an analytical solution of Fick's second law of diffusion, it was
      shown that the early phase of PS-ODN and PS-ODN-PEI complex release was primarily
      controlled by pure diffusion, irrespectively of the type of microsphere. Finally,
      microspheres containing antisense TGF-beta2 nanosized complexes were shown, after
      subconjunctival administration to rabbit, to significantly increase intracellular
      penetration of ODN in conjunctival cells and subsequently to improve bleb
      survival in a rabbit experimental model of filtering surgery. These results open
      up interesting prospective for the local controlled delivery of genetic material
      into the eye.

PMID- 16644055
TI  - Elevated temperature accelerated release testing of PLGA microspheres.
AB  - Drug release from four different poly(lactic-co-glycolic) acid (PLGA) microsphere
      formulations was evaluated under "real-time" (37 degrees C) and accelerated
      release testing conditions of elevated temperature (45, 53, 60 and 70 degrees C)
      and increase in flow rate (4-35 ml/min) using United States Pharmacopeia (USP)
      apparatus 4. Formulation 5 K (composed of low Mw PLGA) exhibited diffusion
      controlled kinetics in "real-time". Whereas, formulations 25 K, 28 K and 70 K
      (composed of medium and high Mw PLGA) followed erosion-controlled kinetics at 37
      degrees C. Temperature-induced degradation of the microspheres was studied by
      monitoring drug release rates, change in molecular weight and morphological
      changes. Drug release rates at elevated temperature were used to predict "real
      time" release applying the Arrhenius equation. The energy of activation for
      dexamethasone release from PLGA microspheres was calculated as 19.14 kcal/mol.
      Molecular weight change measured by gel permeation chromatography followed first
      order kinetics for both "real-time" and accelerated release. All four
      formulations exhibited morphological changes (such as surface pore closing and
      geometry change) at elevated temperature with consequent reduction in burst
      release.

PMID- 16644056
TI  - Evaluation of a new blood glucose monitoring system with auto-calibration for
      home and hospital bedside use.
AB  - A new self-calibrating blood glucose monitoring system (BGMS) was evaluated in a
      series of clinical studies with both ambulatory subjects and with hospitalized
      patients. The new BGMS requires a 0.6microL sample volume, provides results in
      15s, and uses a glucose dehydrogenase chemistry that is oxygen independent. In
      the first study, Ascensia Contour meters calibrated to whole blood were tested by
      health care professionals (HCP) and lay users at two clinical sites. Both HCPs
      and lay users obtained results that fulfilled the ISO 15197:2003 criteria that
      95% of self-monitoring blood glucose (SMBG) measurements should fall within +/
      20% (for blood glucose (BG) concentrations> or =4.2mmol/L or +/-0.83mmol/L for BG
      concentrations<4.2mmol/L) of the laboratory value. Lay users and HCPs obtained
      97.2 and 96.7% of glucose results within ISO criteria, respectively. In a second
      study, HCPs assayed blood samples from patients at the hospital bedside using
      meters calibrated to give whole blood glucose and meters calibrated to give
      plasma glucose results. Overall, 94.7% of the measurements met the ISO 15197:2003
      criteria. Most lay subjects rated the BGMS as either excellent or very good in a
      questionnaire, and were able to use it properly without training. These findings
      indicate that this new BGMS is a convenient and accurate instrument system
      suitable for both hospital bedside use by HCPs and for SMBG by people who
      routinely monitor their blood glucose.

PMID- 16644057
TI  - Diagnostic thresholds for diabetes: the association of retinopathy and
      albuminuria with glycaemia.
AB  - AIM: We examined the association of fasting plasma glucose (FPG), 2-h plasma
      glucose (2hPG) and HbA1c with retinopathy and microalbuminuria using both deciles
      of glycaemia and change point models, to validate current diagnostic criteria for
      diabetes and to identify therapeutic thresholds for glycaemic control. METHODS:
      The Australian Diabetes Obesity and Lifestyle study (AusDiab), conducted in 1999
      2000, included adults aged > or =25 years from 42 randomly selected areas of
      Australia. Retinopathy and albuminuria were assessed in participants identified
      as having diabetes (based on self report and oral glucose tolerance test),
      impaired fasting glucose, impaired glucose tolerance and in a random sample with
      normal glucose tolerance. Data were available for 2,182 participants with retinal
      photographs and 2,389 with urinary albumin/creatinine results. RESULTS: The
      prevalence of retinopathy in the first 8 deciles of FPG and HbA1c and the first 9
      deciles of 2hPG were 7.2, 6.6, and 6.3%, respectively and showed no variation
      with increasing glucose or HbA1c. Above these levels, the prevalence rose
      markedly to 18.6% in the top 2 deciles of FPG, 21.3% in the top 2 deciles of
      HbA1c and 10.9% in the top decile of 2hPG. The thresholds for increasing
      prevalence of retinopathy were 7.1 mmol/l for FPG, 6.1% for HbA1c and 13.1 mmol/l
      for 2hPG. The prevalence of microalbuminuria rose gradually across deciles of
      each glycaemic measure. Thresholds were less clear than for retinopathy, but were
      seen at a FPG of 7.2 mmol/l and HbA1c of 6.1%, with no evidence of a threshold
      effect for 2hPG. CONCLUSIONS: The prevalence of retinopathy rose dramatically in
      the highest deciles of each glycaemic measure, while for microalbuminuria the
      increase of prevalence was more gradual. The FPG values corresponded well with
      the WHO diagnostic cut-point for diabetes, however the 2hPG value did not. HbA1c
      thresholds were similar for both retinopathy and microalbuminuria and compared
      well to values shown in other studies. These results support current targets for
      FPG and HbA1c in preventing microvascular complications.

PMID- 16644058
TI  - Cooperative IFN-gamma production of mouse liver B cells and natural killer cells
      stimulated with lipopolysaccharide.
AB  - BACKGROUND/AIMS: Although mouse liver contains a large population of B cells,
      little is known about how hepatic B cells respond to bacterial lipopolysaccharide
      (LPS). METHODS: The cytokine and IgM productions of hepatic B cells were compared
      with those of splenic B cells. The effect of LPS-treated hepatic B cells on IFN
      gamma production from co-cultured NK1.1+ cells was also examined by irradiation
      and transwell experiments. RESULTS: Hepatic B cells stimulated with LPS produced
      substantial amounts of IFN-gamma and IL-12 but a small amount of IgM, while
      splenic B cells did not produce any of these cytokines but produced a large
      amount of IgM. The hepatic B cells expressed surface markers similar to those on
      spleen B cells but expressed more C-X-C chemokine receptor 3 than spleen B cells.
      Notably, depletion of B220+ cells from liver MNCs (but not from spleen MNCs)
      greatly decreased LPS-induced IFN-gamma production. Furthermore, LPS-treated
      hepatic B cells stimulated liver NK1.1+ cells to produce a remarkable amount of
      IFN-gamma, not only through their soluble factors but also through direct cell
      cell contact. CONCLUSIONS: Liver B cells may play an important role in the
      defense against gram-negative bacterial infections by inducing IFN-gamma
      production from liver NK cells.

PMID- 16644059
TI  - Gene expression profiling of renal dysfunction in rats with experimental
      cirrhosis.
AB  - BACKGROUND/AIMS: Renal dysfunction is a frequent complication in advanced
      cirrhosis. The mechanisms underlying this complication have classically been
      addressed through conventional methods of study of candidate genes, but never on
      a genome-wide scale. In this investigation, we used microarrays to monitor global
      gene expression changes in the kidney of cirrhotic rats. METHODS: Renal samples
      were obtained from control and carbon tetrachloride-induced cirrhotic rats. RNA
      samples were reverse-transcribed into Cy5-labeled cDNA, combined with a Cy3
      labeled reference and hybridized to oligonucleotide microarrays. Microarrays were
      scanned in a Genepix 4000B and data analyzed by Luminator v2.0 software. RESULTS:
      A total of 620 genes were differentially regulated (354 up and 266 down) in the
      cirrhotic kidney, accounting for approximately 11% of all analyzed transcripts.
      Functional grouping of these genes revealed that 47 were related to the category
      of vascular tone and 85 to transporters/channels. Among these, we identified
      genes and pathways already associated with renal dysfunction as well as a new
      subset of genes previously unknown to participate in this complication, including
      a G protein-coupled receptor that binds apelin, a protein phosphatase
      (calcineurin B) and a number of neuropeptide receptors and growth factors.
      CONCLUSIONS: These findings furnish new data for mechanistic investigation into
      renal dysfunction in cirrhosis.

PMID- 16644060
TI  - Purinergic P2Y2 receptors promote hepatocyte resistance to hypoxia.
AB  - BACKGROUND/AIMS: ATP stimulation of purinergic P2 receptors (P2YR and P2XR)
      regulates several hepatic functions. Here we report the involvement of ATP
      mediated signals in enhancing hepatocyte tolerance to lethal stress. METHODS: The
      protection given by purinergic agonists was investigated in rat hepatocytes
      exposed to hypoxia. RESULTS: ATP released after hypotonic stress (200 mOsm/L) as
      well as P2YR agonists prevented hepatocyte killing by hypoxia with efficiency
      ranking UTP > ATPgammaS > ADPbetaS, whereas the P2XR agonist, methylene-adenosine
      5'-triphosphate, was ineffective. Adenosine-5'-O-3-thiotriphosphate (ATPgammaS;
      100 micromol/L) also prevented Na+ -overload in hypoxic cells by inhibiting the
      Na+/H+ exchanger, without interfering with hypoxic acidosis. ATPgammaS activated
      Src and promoted a Src-dependent stimulation of both ERK1/2 and p38MAPK. Blocking
      p38MAPK with SB203580 reverted the protection given by ATPgammaS on both cell
      viability and Na+ accumulation, whereas ERK1/2 inhibition with PD98058 was
      ineffective. An increased phosphorylation of ERK1/2 was also evident in untreated
      hypoxic hepatocytes. PD98058 ameliorated Na+ accumulation and cell death caused
      by hypoxia. Hepatocyte pre-treatment with ATPgammaS reverted ERK1/2 activation in
      hypoxic cells. SB203580 blocked the effects of ATPgammaS on both ERK1/2 and
      Na+/H+ exchanger. CONCLUSIONS: The activation of p38MAPK by P2Y2R increases
      hepatocyte resistance to hypoxia by down-modulating ERK1/2-mediated signals that
      promote Na+ influx through the Na+/H+ exchanger.

PMID- 16644061
TI  - Evaluation of ischemic injury of the cardiac tissue by using the principal
      component analysis of an epicardial electrogram.
AB  - Monitoring and control of the heart tissue viability is of crucial importance
      during heart surgery operations. In most cases the heart tissue suffers from an
      ischemic injury that causes a decrease in the velocity of electrical excitation
      propagation in it and influences the shape of the excitation wave front that
      spreads over the injured area. It is reflected in a more complex shape of the
      registered epicardial electrogram as compared to normal. A method for
      quantitative evaluation of the complexity of the shape of the epicardial
      electrogram based on the principal component analysis is here proposed for
      evaluation of the ischemic injury of the cardiac tissue. A minimal, yet
      sufficient, number of the principal components (the optimal basis functions) for
      truncated expansion of the epicardial electrogram signals could be used as an
      estimate of signal complexity. The method for determination of such a minimal,
      yet sufficient, number of principal components were developed by using epicardial
      electrograms registered during in situ experiments on dogs in which local
      ischemia was evoked by ligation of a coronary vessel.

PMID- 16644062
TI  - Lung cancer with chest wall involvement: predictive factors of long-term survival
      after surgical resection.
AB  - Multimodal management of lung cancer extending to chest wall and type of surgical
      procedure to be performed are still debated. The aim of this retrospective
      analysis was to analyze the predictive factors of long-term survival after
      surgery, focusing on depth of infiltration, type of surgical intervention and
      possible role of preoperative therapies, comparing survival of these patients
      with that of a group of patients affected by a Pancoast tumour and surgical
      treated in the same period. MATERIALS AND METHODS: We reviewed records of 83
      consecutive patients with NSCLC in stage T3 (owing to direct extension to chest
      wall), who underwent surgical resection in our Thoracic Surgery Unit between
      January 1994 and December 2003. Patients were classified in two groups: pancoast
      tumours (PT) or chest wall extending tumours (CW): survival and prognostic
      factors of each category were analyzed. RESULTS: In the CW group we had 68
      patients: 45 were in stage IIB (pT3N0), 23 in stage IIIA (pT3-N1-2). Histology
      revealed adenocarcinoma in 23 cases, squamous cell carcinoma in 34, large cells
      anaplastic carcinoma in 8, adenosquamous carcinoma in 3. An involvement of chest
      wall tissues beyond the endothoracic fascia was found in 21 patients, while in
      the remaining 47 the invasion of chest wall tissues was confined to the parietal
      pleura. An extrapleural dissection was performed in 48 patients while combined
      pulmonary and chest wall en bloc resection was required in 20 patients. Resection
      was incomplete in three cases. In the PT group we had 15 patients: 11 were in
      stage IIB and 4 in stage IIIA. Histological type was adenocarcinoma in 10 cases,
      squamous cell carcinoma in 4 and adenosquamous carcinoma in 1. A univariate
      analysis performed in the CW group showed that survival was significantly
      affected by nodal status, stage, extension of chest wall invasion, type of lung
      resection and residual disease. In a multivariate analysis we found that nodal
      status, completeness of resection and extension of chest wall involvement
      maintained a significant prognostic value. There was no difference between the
      survival curve of CW and PT group: considering the two subset of CW patients, on
      the basis of depth of infiltration, survival of PT patients was significantly
      better than that of CW patients with involvement of muscular tissues and ribs
      (p=0.02). CONCLUSION: Nodal status, radical resection and depth of chest wall
      infiltration are the main predictive factors affecting long-term survival, while
      surgical procedure does not impact on it if margins of resection are free from
      disease. The better survival observed in PT patients let us to hypothesize that
      an induction chemo-radiation therapy, as routinely administered to PT patients,
      could have a potential benefit in survival of patients with CW tumour extending
      beyond parietal pleura.

PMID- 16644063
TI  - Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia
      cell lines.
AB  - Thymosin alpha1 (Talpha1), a 28-amino acid peptide, is a well-known immune system
      enhancer for the treatment of various diseases. In the present investigation, the
      effects of Talpha1 on the proliferation and apoptosis of human leukemia cell
      lines (HL-60, K562 and K562/ADM) were studied. The proliferation was
      significantly depressed after 96 h of treatment with Talpha1, and obvious signs
      of apoptosis, i.e., cell morphology, nuclei condensation and Annexin V binding,
      were observed thereafter. Moreover, the up-regulation of Fas/Apol (CD95) and
      decrease in bcl-2 anti-apoptotic gene expression were observed in apoptotic
      cells. The expression and the function of P-glycoprotein (P-gp) can be slightly
      inhibited by Talpha1. It is noteworthy that K562 and K562/ADM were more sensitive
      than HL-60 cells when subjected to Talpha1. Furthermore, HepG-2, the human
      hepatoma cell line, displayed significant less sensitivity to Talpha1 than all
      the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine
      receptors (nAChRs) antagonist, significantly antagonized the inhibition effects
      induced by Talpha1, whereas atropine, a muscarinic acetylcholine receptor
      antagonist, did not exhibit such effects. All the results indicate that Talpha1
      was able to significantly suppress proliferation and induce apoptosis in human
      leukemia cell lines.

PMID- 16644064
TI  - Electroacupuncture suppresses expression of gastric ghrelin and hypothalamic NPY
      in chronic food restricted rats.
AB  - Electroacupuncture (EA) has been reported to reduce body weight in overweight
      subjects in clinical practice, as well as in rats and mice with diet-induced
      obesity. In the present study, this effect of EA was tested in lean rats
      subjected to long-term food restriction (FR, food was offered only 1 h/day). Two
      hertz EA administered once every other day produced a further reduction in body
      weight in FR rats. Exploration of the mechanism involved revealed significant
      downregulation of the orexigenic peptides: ghrelin in the stomach, and
      neuropeptide Y (NPY) but not Agouti-related peptide (AgRP) in the hypothalamus,
      which was in line with the reduction in food intake in rats receiving EA
      stimulation as compared with those receiving restraint only. Uncoupling protein 3
      (UCP3), involved in accelerating energy expenditure, was not significantly
      altered. These results suggest that the EA-induced body weight reduction was due
      mainly to a decrease in food intake rather than an increase in energy
      expenditure. A reduction in the orexigenic peptides ghrelin and NPY may be
      involved in the underlying mechanism.

PMID- 16644065
TI  - Computational approaches for predicting CYP-related metabolism properties in the
      screening of new drugs.
AB  - The site of biotransformation, the extent and rate of metabolism and the number
      of active metabolic pathways are among the most important characteristics of the
      pharmacokinetics of a drug. The catalytic activity of drug metabolizing enzymes
      is likely the most influential determinant of the pharmacokinetic variability.
      Metabolic stability is the prerequisite for sustaining the therapeutically
      relevant concentrations. Metabolic inhibition and induction can give rise to
      clinically important drug-drug interactions. A variety of computational
      approaches are currently available for predicting different cytochrome P450 (CYP)
      related metabolism endpoints. The present review will describe these approaches
      and their impact on drug development process. Indications on the available
      software for the implementation will also be given.

PMID- 16644066
TI  - [The concept of allergy surveillance: action of the allergy surveillance
      network].

PMID- 16644067
TI  - [53rd French Congress of Internal Medicine, Nancy, France, 15-17 June 2006.
      Proceedings and abstracts].

PMID- 16644068
TI  - [Cutaneous leishmaniasis in polymyositis].
AB  - INTRODUCTION: The prevalence of cutaneous leishmaniasis is increasing, especially
      in immunocompromized subjects. CASE RECORD: We report a case of particular
      interest, where a patient with steroid refractory polymyositis developed
      cutaneous leishmaniasis. Clinical outcome was favorable after institution of
      intralesional antimony therapy. DISCUSSION: Cutaneous leishmaniasis is still
      recognized to be an opportunistic infection. Its frequency is indeed higher in
      immunocompromized subjects, mainly HIV-infected patients. In our patient, both
      polymyositis and steroid therapy were predisposing factors of cutaneous
      leishmaniasis onset; prednisone therapy has been postulated to be associated with
      immune dysfunction leading to: reduced blood T cells' levels (CD4 et CD8) as well
      as decreased cytokine synthesis (e.g. interferon gamma).

PMID- 16644069
TI  - [Contribution of molecular biology to the diagnosis and treatment of allergies].

PMID- 16644070
TI  - Immunisation of a cohort Pacific children living in New Zealand over the first 2
      years of life.
AB  - Pacific children have had consistently evidenced low rates for routine childhood
      immunisations. Using the Pacific Islands Families: First 2 Years of Life cohort
      study, we investigated the immunisation rate of Pacific infants residing in New
      Zealand at 24-months postpartum. Full immunisation was reported for 89% of
      infants, substantially increased from the 53% found in the 1992 national survey
      and closer to the New Zealand Ministry of Health's target of 95%. Increased
      parity and maternal smoking were associated with incomplete child immunisation
      status. Initiatives to increase immunisation rates amongst Pacific children
      appear to be succeeding and warrant continuation.

PMID- 16644071
TI  - Influenza vaccination in healthy children.

PMID- 16644072
TI  - Assessment of state-of-the-art models for predicting the remobilisation of
      radionuclides following the flooding of heavily contaminated areas: the case of
      Pripyat River floodplain.
AB  - The performances of models are assessed to predict the wash-off of radionuclides
      from contaminated flooded areas. This process should be accounted for in the
      proper management of the aftermath of a nuclear accident. The contamination of
      the Pripyat River water following the inundation of a floodplain heavily
      contaminated by (90)Sr and (137)Cs of Chernobyl origin is used as the basis for
      modelling. The available experimental evidence demonstrated that remobilisation
      of radiostrontium is an important process implying a significant secondary
      radioactive load of water flowing over the contaminated floodplain. On the
      contrary, there is no empirical evidence of a similar behaviour for radiocaesium.
      In general, state-of-the-art models properly predicted the remobilisation of
      strontium, whereas they significantly overestimated radiocaesium concentrations
      in water. The necessary model improvements for a more accurate prediction of
      radiocaesium contamination levels include a reassessment of the values of the
      model parameters controlling the remobilisation process.

PMID- 16644073
TI  - The politics of evidence as the basis for change.

PMID- 16644074
TI  - The distribution of bone islands and juxta-articular bone cysts in the growing
      hand.
AB  - Bone islands and juxta-articular bone cysts are relatively common incidental
      findings when X-rays are taken for other purposes. We have identified that the
      incidence of bone islands in the hands of asymptomatic children between the ages
      of 5 and 13 years is 3.8% and the incidence of cysts in the same population is
      2.8%. Bone islands were most common in the scaphoid, whilst juxta-articular bone
      cysts were most common in the capitate. The age at which they appear has not been
      reported previously. This study first identifies their presence in the hands of
      children of age 10 years and 2 months (bone islands) and 10 years 0 months (juxta
      articular bone cysts). Most of the lesions were already present on the first
      radiograph taken. New bone islands appeared in five cases between the ages of 13
      years and 1 month and 15 years and 3 months. New juxta-articular bone cysts were
      observed to appear in five cases between the ages of 10 years 10 months and 15
      years 0 months. No island or cyst changed in size during the review period.

PMID- 16644075
TI  - Scaphotrapeziotrapezoid osteoarthritis associated with minor radial longitudinal
      deficiency.

PMID- 16644076
TI  - Ensuring quality of in vitro alternative test methods: Current practice.
AB  - In Vitro toxicology methods are being validated and adopted by regulatory
      agencies for use as alternatives to animal testing. Such methods may use ex vivo
      tissues or bioconstructs, some of which may be proprietary. Users of the data
      from these methods need to be reassured that the assays or assay components used
      in their studies provide consistent, good quality data over time, matching the
      standards achieved during the validation process. This paper presents an overview
      of approaches currently used by representatives of a manufacturer and a contract
      testing laboratory to ensure that the results from in vitro alternative methods
      are reproducible and of high quality over time. These approaches include full
      characterization of cells or tissues, sampling of each lot of manufactured
      bioconstructs for performance, and regular use of controls and benchmark
      chemicals to provide assurance of consistency of assay performance.

PMID- 16644077
TI  - Sex differences in the effect of education on depression: resource multiplication
      or resource substitution?
AB  - Does education improve psychological well-being more for one sex than for the
      other? Resource substitution theory hypothesizes that education improves well
      being more for women, because socioeconomic disadvantage makes them depend more
      on education to achieve well-being. Resource multiplication implies the opposite,
      that education improves well-being more for men, because they get bigger labor
      market payoffs from it such as authority and earnings. Data from a 1995 survey of
      US adults with follow-ups in 1998 and 2001 support the resource substitution
      hypothesis. Depression decreases more steeply for women than for men as the level
      of education increases. The gender gap in depression essentially disappears among
      persons with a college degree or higher. Two mediating interactions appear to
      account for the convergence. Education increases work creativity more sharply for
      women than for men, thereby reducing depression. Education increases the sense of
      control for both sexes equally, but depression declines more steeply for women as
      sense of control increases. Growth curve analyses of depression vectors confirm
      the resource substitution pattern. The adulthood life course pattern of
      depression levels and changes depends more strongly on education for women than
      for men.

PMID- 16644078
TI  - What "Dr. Mom" ordered: a community-based exploratory study of parental self-care
      responses to children's ADHD symptoms.
AB  - Little is known about family initiated self-care interventions in response to
      symptoms of attention deficit/hyperactivity disorder (ADHD), and how self-care
      may co-exist with professional treatments. This paper explores parental self-care
      strategies for children with hyperactivity or attention problems, and examines
      factors and domains that influence their use from the mixed method perspective.
      As part of a longitudinal cohort study of ADHD detection and service use,
      caregivers of a representative US community sample of 266 children at high risk
      for ADHD completed a questionnaire that assessed five self-care strategies
      (behavior modification, coping, diet, over-the-counter medication use and
      religious practices), and made open-ended inquiry about discipline changes in
      response to behavioral concerns. Questionnaire responses were analyzed using
      logistic regression approaches. Open-ended answers were open coded; secondary
      analysis followed Spradley's model of domain analysis. Quantitative findings
      showed that behavior modification was the most commonly tried self-care strategy,
      followed by coping, diet, and religious practices. Over-the-counter trial was
      least common. The parents of professionally treated children were more likely to
      have employed behavior modification, coping strategies and over-the-counter
      medications than the parents of untreated children. Two-thirds of parents had
      changed their disciplinary action within three domains that were identified
      through qualitative analysis, including changes related to (a) the prevention of
      disciplinary problems (e.g., sustain eye contact, activation, consistency, clear
      instructions), (b) the solution of disciplinary problems (e.g., time-outs;
      privilege removal), and (c) parental coping associated with disciplinary problems
      (e.g., control own emotions, become less judgmental and more tolerant, and
      develop more appropriate expectations). These findings suggest that self-care
      strategies are commonly employed and appear to co-exist with professional
      treatment. Therefore, healthcare providers should actively explore parents' use
      of such strategies as some of them may interfere with prescribed treatments
      (e.g., over-the-counter) or absorb parental resources without likely benefit
      (e.g., diet).

PMID- 16644079
TI  - The influence of maternal childhood and adulthood social class on the health of
      the infant.
AB  - The aim of this study is to investigate how maternal childhood and adulthood
      social class contribute to social inequalities in low birth weight, neonatal
      mortality and postneonatal mortality. In particular I consider the combined
      influence of childhood and adult class, and compare outcomes with regard to the
      time distance from birth. Analyses were performed on a large sample of Swedish
      births from 1973 to 1990, restricted to infants of women with both childhood and
      adult class, classified as manual or non-manual. Logistic regression is used to
      compare odds ratios for social classes. The results indicate that manual maternal
      childhood class is consistently associated with higher risks for low birth weight
      and neonatal mortality, even when adult class was adjusted for. The influence of
      adult class was greater than that of childhood class for all health outcomes.
      Compared to higher/middle non-manual workers, unskilled workers in the service
      sector and workers in the manufacturing sector displayed the highest odds ratios
      for all adverse health outcomes. When both childhood and adult class were taken
      into account, social differences were greater for low birth weight and neonatal
      mortality than for postneonatal mortality. Maternal childhood class had more
      influence on low birth weight and neonatal mortality than on postneonatal
      mortality. I conclude that maternal childhood and adulthood social class are both
      independently associated with inequalities in health-related birth outcomes, and
      that social differences are greater for health outcomes closer to birth.

PMID- 16644080
TI  - Understandings of Down's syndrome: a Q methodological investigation.
AB  - Down's syndrome has been, and continues to be, a central focus of prenatal
      testing technology. However, there has been surprisingly little examination of
      how parental understandings of the condition relate to prenatal testing choices.
      This study, carried out at the University of Leeds, uses Q methodology to
      identify 'competing equivalent stories' of Down's syndrome and to highlight the
      shared and distinct themes within these stories. Seventy-six people were selected
      as being likely to represent a diverse range of views about Down's syndrome,
      approximately half of whom had some known experience or expertise related either
      to the condition or to prenatal testing. The participants were asked to Q sort 50
      propositions about Down's syndrome that were selected to reflect different views
      about the condition in terms of its impact on the affected person, on families
      with an affected child, and on society. Using Principal Components Analysis, five
      statistically independent factors were extracted that reflected a range of views
      towards, and experiences of, people with Down's syndrome. Despite a virtual
      consensus about the rights of existing people with Down's syndrome to healthcare,
      an education, and inclusion in their community, there were significant
      differences in how participants believed they personally would adjust to an
      affected child. Furthermore, whether or not people with Down's syndrome were seen
      to be within 'a continuum of normality' sheds light on how views about the
      condition may be linked to views about prenatal testing and termination of
      pregnancy. The study demonstrates that people hold complex and sometimes
      seemingly contradictory views about Down's syndrome, and that these are likely to
      influence their prenatal testing decisions. Antenatal settings currently provide
      little opportunity for people to discuss and explore their beliefs about
      disability. It is argued that this may affect the ability of some individuals to
      make decisions that are informed by their own views and values.

PMID- 16644081
TI  - US state- and county-level social capital in relation to obesity and physical
      inactivity: a multilevel, multivariable analysis.
AB  - Although social capital has been linked to a variety of health outcomes, its
      association with obesity has yet to be elucidated. This study explored the
      relations between social capital measured at the US state and county levels and
      individual obesity and leisure-time physical inactivity. Individual-level data
      were drawn from the 2001 Behavioral Risk Factor Surveillance System survey, while
      data from other surveys and administrative sources were used to construct
      contextual measures. Two state-level social capital scales were derived from 10
      indicators and two county-level scales from five indicators. In 2-level analyses
      of over 167,000 adults nested within 48 states plus the District of Columbia,
      residence in a state above the median on one or both state social capital scales
      (vs. neither scale) was associated with lower relative odds of obesity and
      physical inactivity, controlling for individual-level covariables and state-level
      estimates of mean household income, the Gini coefficient, and the percentage of
      Black residents. In 3-level analyses, the adjusted odds ratio (OR) for physical
      inactivity associated with residence in a county above the median on one or both
      county social capital scales was significantly below 1, while the association
      with obesity was not significant. Significantly weaker inverse ORs for the
      relations between state- and county-level social capital and obesity were
      observed among American Indians/Alaska Natives compared to Whites. Meanwhile,
      little support was found for mediation by social capital of the associations of
      urban sprawl and income inequality with obesity or physical inactivity. Overall,
      this study provides some evidence for the promotion of social capital as a
      potential strategy for addressing the burgeoning obesity epidemic.

PMID- 16644082
TI  - High-dose of multiple antipsychotics and cognitive function in schizophrenia: the
      effect of dose-reduction.
AB  - We evaluated the effect of antipsychotic dose-reduction on the neurocognitive
      function of 17 schizophrenic patients (11 male and 6 female, mean age=42.4+/
      11.3) who have been taking high-doses of multiple conventional antipsychotics.
      The mean (+/-SD) of total daily antipsychotic doses (in mg/day, chlorpromazine
      equivalent) was 2,253 (+/-668) at baseline, which was reduced to 1,315 (+/-276).
      Possible changes in neurocognitive function were assessed using Wisconsin card
      sorting test (WCST) and continuous performance test (CPT). As controls, we
      examined WCST and CPT in 6 schizophrenic patients (4 male and 2 female, mean
      age=47.7+/-14.2) who had been taking high-doses of multiple antipsychotics (mean
      daily antipsychotic dose=1,753+/-165 mg) and declined to change their
      antipsychotic regimen. In WCST, the mean number of total correct answers
      significantly increased (53.2+/-16.3 vs. 63.8+/-19.6, P=0.035, Wilcoxon signed
      rank test); perseverative errors significantly decreased (54.4+/-27.3 vs. 35.4+/
      20.1, P=0.013, Wilcoxon signed rank test) after the antipsychotic dose-reduction.
      In contrast, the control group showed no significant difference between the two
      WCST performances conducted with a three-month interval. The improvements in WCST
      performance significantly correlated with the decreases in PANSS negative
      syndrome score in the subject patients. No significant change was observed in CPT
      performances in either group. Our preliminary data shows that, in schizophrenic
      patients taking high-doses of multiple conventional antipsychotics, dose
      reduction might lead to improvements in cognitive functions.

PMID- 16644083
TI  - Midbrain binding of [123I]nor-beta-CIT in atypical depression.
AB  - BACKGROUND: Altered serotonin (SERT) and dopamine transporter (DAT) densities
      have been recorded in major depression. Atypical depression (ATD) has been
      suggested to be connected to decreased serotonergic transmission, but no studies
      have been published on the association between brain serotonin transporter
      density and ATD. METHODS: PATIENTS with depression (n=29) were divided into three
      groups according to DSM-IV criteria: atypically depressed, melancholic patients,
      and "undifferentiated" patients. Depressive symptoms were evaluated with the 29
      item Hamilton Depression Rating Scale (HAM-D-29). Single photon emission computed
      tomography (SPECT) with [(123)I]nor-beta-CIT was used to evaluate serotonin
      transporter density (SERT) in the midbrain and dopamine transporter density (DAT)
      in the striatum of patients and healthy controls (n=18). RESULTS: All subgroups
      except those with undifferentiated depression had lower SERT densities compared
      to controls. No significant differences were found in the densities between the
      subgroups. Atypical scores of HAM-D-29 were associated with SERT densities in the
      midbrain (beta=-0.40, t=-2.3, p=0.03), even after adjustment for age, gender and
      HAM-D-21 scores (beta=-0.39, t=-2.32, p=0.03). CONCLUSIONS: The association
      between atypical scores of HAM-D-29 and midbrain SERT densities suggests a
      relationship between serotonergic dysfunction and ATD.

PMID- 16644084
TI  - The four-plates test: anxiolytic or analgesic paradigm?
AB  - The four-plates test (FPT) is an animal model of anxiety in which the exploration
      of the novel surroundings is suppressed by the delivery of a mild electric foot
      shock. The anti-nociceptive system has been reported to be activated by a variety
      of stressful stimuli such as footshock. The present study was thus designed to
      compare effects of drugs in the FPT and in the hot-plate test (an animal model of
      pain), in order to disambiguate the drug-induced anti-punishment effects obtained
      in the FPT from alterations in pain sensitivity. Various compounds, known to be
      implicated in anxiety states as well as nociception, have been studied. Although
      morphine induced a strong anti-nociceptive effect, it did not modify the number
      of shocks received in the FPT. Alprazolam and diazepam induced an anxiolytic-like
      effect in the FPT, at doses that did not induce any effect in the hot-plate test.
      The antidepressants previously reported anxiogenic (desipramine, maprotiline) in
      the FPT were found to be analgesic at the same doses. Milnacipran, venlafaxine
      and paroxetine did not modify the pain threshold, whereas they have previously
      been shown to induce anxiolytic-like effects in the FPT. The dopaminergic
      antidepressant agent nomifensine was without effect on both tests. Our results
      suggest that the reported drug-induced anti-punishment effects in the FPT are not
      related to modifications of pain threshold but to a pure anxiolytic-like effect.

PMID- 16644085
TI  - Abnormal neurological signs, visual contrast sensitivity, and the deficit
      syndrome of schizophrenia.
AB  - This study was designed to investigate the relationship between abnormal
      neurological signs, visual contrast sensitivity, and the deficit syndrome of
      schizophrenia. Visual contrast sensitivity for counterphase-modulated low spatial
      frequency gratings was measured in 32 non-deficit and 12 deficit schizophrenia
      patients and 20 healthy controls subjects. Abnormal neurological signs were
      evaluated with the Neurological Evaluation Scale (NES). Compared with the
      controls, patients with schizophrenia displayed impaired visual contrast
      sensitivity, which was associated with sensory integration deficits, as measured
      with the NES. The deficit syndrome was predicted by negative symptoms and sensory
      integration deficits. These results suggest that early-stage perceptual
      dysfunctions, which may reflect the abnormality of precortical magnocellular
      visual pathways, are related to a specific group of abnormal neurological signs.

PMID- 16644086
TI  - Mirtazapine inhibits salivary cortisol concentrations in anorexia nervosa.
AB  - The antidepressant mirtazapine has been demonstrated to acutely inhibit cortisol
      concentrations in healthy subjects and depressed patients. Since both depressed
      and anorectic patients are characterized by hyperactivity of the hypothalamo
      pituitary-adrenocortical (HPA) system, the clinical usefulness and the
      endocrinological effects of mirtazapine were investigated in anorexia nervosa
      (AN). Five female patients suffering from AN restricting subtype (DSM-IV
      criteria) were admitted to a closed ward and treated with mirtazapine for three
      weeks receiving 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg
      mirtazapine per day from day 2 up to the end of the study (day 21). Besides
      weekly determination of clinical parameters (Body Mass Index [BMI], Hamilton
      Depression Rating Scale [21-HAMD]), salivary cortisol concentrations were
      measured before treatment (day - 1), at the beginning of treatment (day 0), after
      1 week (day 7), and after 3 weeks (day 21) of treatment with mirtazapine. Saliva
      samples were collected hourly from 0800 up to 1,400 h. Repeated-measures ANOVA
      revealed a significant inhibition of salivary cortisol levels during 3-week
      treatment with mirtazapine (p<0.05) which became obvious already after the first
      mirtazapine administration (day 0). Moreover, a trend for an increase in BMI was
      seen (p=0.063), whereas no significant changes in 21-HAMD sum scores could be
      demonstrated. Double-blind, placebo-controlled studies are needed to clarify the
      question whether the observed changes in BMI are related to the mirtazapine
      induced attenuation of HPA axis activity or whether they are due to monitoring of
      food intake and purgative behaviour on the closed ward.

PMID- 16644087
TI  - Neurotoxicity of Coscinium fenestratum stem, a medicinal plant used in
      traditional medicine.
AB  - Coscinium fenestratum is a common medicinal plant widely used in the Indochina
      region, but scientific data on its safety is very limited. This study aimed to
      observe the effect of this plant on neurotoxicity and neurobehavior. Oral
      administration of plant alcoholic extract at dosages of 5, 10 and 20 mg/kgBW for
      14 days increased the rats body weight and decreased the neuron density in the
      cerebral cortex, hippocampus and striatum. The plant extract significantly
      increased stereotyped behavior in licking but did not cause anxiolytic activity,
      anti-depression, sensory motor co-ordination impairment and ataxia. It is
      concluded that the plant possesses neurotoxicity and is able to induce
      neurobehavioral changes in rats. Therefore, the application of this plant as
      either drug or supplementary food should be reconsidered.

PMID- 16644088
TI  - Differential response of iron metabolism to oxidative stress generated by
      antimycin A and nitrofurantoin.
AB  - The close interrelationship of oxidative stress and iron is evident by the
      influence of intracellular reactive oxygen species on iron metabolism. Oxygen
      radicals can lead to release of iron from iron-sulfur proteins and ferritin, and
      can damage iron-containing enzymes such as mitochondrial aconitase. Treatment of
      HepG2 human hepatoma cells with antimycin A has two effects relating to iron
      depending on the concentrations of antimycin A: increase of the labile iron pool
      and stimulation of non-transferrin-bound iron uptake. Whereas the first could
      also be generated with nitrofurantoin, the stimulation of non-transferrin-bound
      iron uptake was only seen with antimycin A and needed considerably higher
      concentrations. Pretreatment of the cells with ebselen, which scavenges
      peroxides, reverted only the effect of nitrofurantoin on the labile iron pool.
      Depletion with iron chelators before or after treatment with antimycin A
      diminished the stimulation of non-transferrin-bound iron uptake. We conclude that
      the generation of oxygen radicals in the mitochondria leads to the liberation of
      iron from mitochondrial enzymes, which enters the labile iron pool. But high
      concentrations of antimycin A leading to the stimulation of non-transferrin-bound
      iron uptake is possibly not related to the inhibition of the respiratory chain.

PMID- 16644089
TI  - Decoding errors and the involvement of the E-site.
AB  - Life depends on the faithful translation of the genetic information into
      proteins. Ribosomes have developed remarkable mechanisms to ensure the accurate
      synthesis of proteins. In the first part of this review various types of
      ribosomal errors and their importance for cell-life are surveyed, while in the
      second part two important aspects of the ribosomal E-site for the accuracy of
      translation are considered: (i) The fact that usually misincorporations are not
      harmful for the cell, since only one in about 400 misincorporations will affect
      the structure and/or function of a protein, is a function of the E-site. (ii) In
      contrast, an extremely harmful translational error is a loss of the reading
      frame, resulting in an immediate loss of the genetic information. Maintenance of
      the reading frame is one of the most remarkable achievements of the ribosome;
      only once in about 30,000 elongation cycles is the reading frame lost. A cognate
      tRNA at the E-site is an essential prerequisite for this high precision.

PMID- 16644090
TI  - Decreased lactoferrin levels in peritoneal fluid of women with minimal
      endometriosis.
AB  - OBJECTIVE: The aim of the study was to evaluate for the presence of lactoferrin
      (LTF) in peritoneal fluid (PF) of women with and without endometriosis. PATIENTS:
      Seventy-eight women were studied, including 49 women with endometriosis and, as a
      reference group, 29 patients with functional follicle ovarian cysts. RESULTS:
      Lactoferrin levels were detectable in all peritoneal fluid samples. Women with
      minimal endometriosis had lower PF lactoferrin concentrations compared to both
      patients with high revised American Fertility Society classification scores and
      women with follicle ovarian cysts. No significant difference in the peritoneal
      LTF levels was found between patients with stage II endometriosis, stage III or
      IV endometriotic disease and women with functional cysts of ovaries. CONCLUSIONS:
      Owing to its antibacterial properties lactoferrin is probably an important
      defense factor in the peritoneal cavity, however its role in the pathogenesis of
      endometriosis remains enigmatic.

PMID- 16644091
TI  - A density functional theory study on the role of His-107 in arylamine N
      acetyltransferase 2 acetylation.
AB  - Arylamine N-acetyltransferases (NATs, EC 2.3.1.5) catalyze an acetyl group
      transfer from acetyl coenzyme A (AcCoA) to primary arylamines, and are
      responsible for the biotransformation and metabolism of drugs, carcinogens, etc.
      Structure analysis revealed that His-107 was likely the residue accountable for
      mediating acetyl transfer. We have examined the full catalytic mechanism of this
      system by means of DFT method. The results indicate that if the acetyl group
      directly transferred from the donor, p-nitrophenyl acetate, to the acceptor,
      cysteine, the high activation energy will be a great hindrance. These energies
      have dropped a little in a range of 20-25 kJ/mol when His-107 is assisting the
      transfer process. However, when protonated His-107 is mediating the reaction, the
      activation energies have dropped about 70-85 kJ/mol. Our calculations strongly
      support an enzymatic acetylation mechanism that experiences a thiolate
      imidazolium pair, which have verified the presumption from experiments.

PMID- 16644092
TI  - In memory of Julian Munson Sturtevant.

PMID- 16644093
TI  - Hemothorax after percutaneous cryoablation of the kidney.
AB  - Pleural effusions have not been reported after percutaneous cryoablation of the
      kidney. In our initial experience, we identified and treated two patients who had
      the complication of hemothorax after percutaneous cryoablation for renal
      malignancy. The occurrence of pleural effusions is frequently related to
      technical aspects of the procedure. The pathogenesis of this serious complication
      is discussed and preventive measures are highlighted.

PMID- 16644094
TI  - The metabolic syndrome and erectile dysfunction: multiple vascular risk factors
      and hypogonadism.

PMID- 16644095
TI  - Whole genome analysis of non-optimal codon usage in secretory signal sequences of
      Streptomyces coelicolor.
AB  - Non-optimal (rare) codons have been suggested to reduce translation rate and
      facilitate secretion in Escherichia coli. In this study, the complete genome
      analysis of non-optimal codon usage in secretory signal sequences and non
      secretory sequences of Streptomyces coelicolor was performed. The result showed
      that there was a higher proportion of non-optimal codons in secretory signal
      sequences than in non-secretory sequences. The increased tendency was more
      obvious when tested with the experimental data of secretory proteins from
      proteomics analysis. Some non-optimal codons for Arg (AGA, CGU and CGA), Ile
      (AUA) and Lys (AAA) were significantly over presented in the secretary signal
      sequences. It may reveal that a balanced non-optimal codon usage was necessary
      for protein secretion and expression in Streptomyces.

PMID- 16644096
TI  - A delayed prey-predator system with parasitic infection.
AB  - This paper analyzes a prey-predator system in which some members of the prey
      population and all predators are subjected to infection by a parasite. The
      predator functional response is a function of a weighted sum of prey abundances.
      Persistence and extinction criteria are derived. The stability of the interior
      equilibrium point is discussed. The role of delay is also addressed. Lastly the
      results are verified through computer simulation. Numerical simulation suggests
      that the delay has a destabilizing effect.

PMID- 16644097
TI  - Mice, melatonin and the circadian system.
AB  - Melatonin effects are discussed by reviewing results from mice with intact or
      disrupted melatonin signaling. Melatonin, the neuroendocrine hand of the clock
      produced in the pineal gland during night, acts upon two receptor subtypes.
      Melatonin receptors are found in the suprachiasmatic nuclei (SCN), hypophysial
      pars tuberalis (PT) and adrenal gland. In SCN, melatonin interacts with PACAP, a
      neuropeptide of the retinohypothalamic tract. Moreover, melatonin acts on the SCN
      to modulate the activity of the sympathetic nervous system. Melatonin is not
      required to maintain rhythmic clock gene expression in SCN. By contrast, the
      rhythmic clock gene expression in PT depends on a melatonin signal interacting
      with adenosine. Melatonin may also affect clock gene protein levels in the
      adrenal cortex and influence adrenal functions. In conclusion, melatonin may
      serve the synchronization of peripheral oscillators by interacting with other
      neuroactive substances. A stress-reducing potency of melatonin needs to be
      explored in further studies.

PMID- 16644098
TI  - The p38 MAPK signaling pathway: a major regulator of skeletal muscle development.
AB  - Skeletal muscle development is regulated by extracellular growth factors that
      transmit largely unknown signals into the cell affecting the muscle-transcription
      program. One intracellular signaling pathway activated during the differentiation
      of myogenic cell lines is p38 mitogen-activated protein kinase (MAPK). As a
      result of modifying the activity of p38 in myoblasts, the pathway proved
      essential for the expression of muscle-specific genes. P38 affects the activities
      of transcription factors from the MyoD and MEF2 families and participates in the
      remodeling of chromatin at specific muscle-regulatory regions. P38 cooperates
      with the myogenic transcription factors in the activation of a subset of late
      transcribed genes, hence contributing to the temporal expression of genes during
      differentiation. Recent developmental studies with mouse and Xenopus embryos,
      substantiated and further extended the essential role of p38 in myogenesis.
      Evidence exists supporting the crucial role for p38 signaling in activating MEF2
      transcription factors during somite development in mice. In Xenopus, p38
      signaling was shown to be needed for the early expression of Myf5 and for the
      expression of several muscle structural genes. The emerging data indicate that
      p38 participates in several stages of the myogenic program.

PMID- 16644099
TI  - Transcription of gonadotropin beta subunit genes involves cross-talk between the
      transcription factors and co-regulators that mediate actions of the regulatory
      hormones.
AB  - The gonadotropins LH and FSH have distinct temporal patterns of expression as a
      result of differential regulation by hormones such as GnRH, steroids and activin.
      This specific regulation is due to diverse sets of transcription factors that are
      recruited to the promoters of these genes, and recruit specific co-activator
      complexes which function to stabilize interactions with the general transcription
      factors and RNA polymerase II, and also to induce covalent modifications of the
      histone tails at these gene loci. As these molecular mechanisms are elucidated,
      the nature of nuclear cross-talk between the various hormonally induced pathways
      is becoming evident, revealing both negative and positive effects of interacting
      transcription factors and co-regulators. This paper will review current knowledge
      on the transcriptional regulation of gonadotropin beta subunit gene expression in
      the chromatin setting, and will present new data pertaining to nuclear cross-talk
      between the various endocrine-induced pathways regulating gonadotropin gene
      transcription.

PMID- 16644100
TI  - The steroidogenic effect of single-chain bovine LH analogs in cultured bovine
      follicular cells.
AB  - Single-chain gonadotropin analogs had been constructed for the purpose of
      structure-function studies and analog design. Incorporation of a spacer derived
      from the carboxyl terminal peptide (CTP) of the choriogonadotropin (CG) beta
      subunit between the tethered subunit domains of the human gonadotropins is
      beneficial for the secretion of the single-chain variants without compromising
      biocactivity. Although the CGbeta subunit containing the CTP domain is expressed
      only in primates and equids, a CTP-like sequence exists in the untranslated
      region of the LHbeta gene of several mammalian species, including the bovine
      species. The CTP encrypted in the bovine LHbeta DNA (designated as 'boCTP') and
      the CTP derived from the human CGbeta subunit (denoted as 'huCTP') served as a
      linker sequence in the design of bovine single-chain luteinizing hormone (LH)
      analogs. The purpose of the present study was to evaluate steroidogenesis in
      cultured bovine theca cells following stimulation with these single-chain
      analogs. The concentration of the LHbetaboCTPalpha and LHbetahuCTPalpha analogs
      in the conditioned media of the expressing CHO cells was three- to six-fold
      higher than that of the "linkerless" LHbetaalpha and LHbeta111alpha variants. The
      four analogs induced androstenedione and progesterone secretion from the primary
      theca cells in a dose-dependent manner, but differences in the steroidogenic
      response were observed. The LHbetaboCTPalpha analog (10 ng/ml) effectively
      induced androstenedione and progesterone secretion over unstimulated levels (4.0-
      and 4.4-fold increase for androstenedione and progesterone, respectively). The
      response to the pituitary bovine LH standard (10 ng/ml) was less pronounced for
      both steroids (two- to three-fold increase over basal levels). The activities of
      LHbetahuCTPalpha, LHbetaalpha and LHbeta111alpha were comparable and sightly
      reduced relative to the LHbetaboCTPalpha activity. The data suggested that
      LHbetaboCTPalpha was ranked as the most potent and this was even more prominent
      when analogs were used at a lower dose (1 ng/ml). These data suggest that the
      design, including the huCTP or boCTP linker, is favorable for the production of
      single-chain bovine LH analogs. Furthermore, spacing of the tethered subunit
      domains with the cryptic boCTP sequence that originated from the bovine LHbeta
      gene appears advantageous for the purpose of stimulating steroid production in
      the species-specific bioassay. Thus, an effective strategy to produce bioactive
      single-chain LH analogs in non-primate, non-equid species would be the mutatation
      of the LHbeta genes with the aim of expressing the cryptic CTP sequence as a
      spacer derived from the DNA of the same organism.

PMID- 16644101
TI  - Gene expression patterns for GDNF and its receptors in the human putamen affected
      by Parkinson's disease: a real-time PCR study.
AB  - Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming
      growth factor-beta superfamily, is a potent trophic factor for dopaminergic
      neurons of the ventral midbrain, which are known to degenerate during Parkinson's
      disease (PD). The neuroprotective, neurorestorative, and stimulatory properties
      of GDNF has prompted numerous suggestions that this trophic factor may be a
      potential therapeutic tool to treat PD, and it has also been widely speculated
      that altered GDNF expression levels may be involved in the pathophysiology of the
      disease. In this study, we have investigated if mRNA expression levels for GDNF
      and/or its receptors are altered during PD in the human putamen, a target area
      for dopamine neurons of the substantia nigra compacta. Expression levels were
      analyzed with quantitative real-time reverse transcriptase polymerase reaction
      (RT qPCR) in post-mortem tissues from PD patients and aged matched controls.
      Primer pairs specific for GDNF (isoforms I and II), and its receptor molecules,
      GFRalpha1 and cRET were utilized. GDNF, cRET and GFRalpha1 mRNA expression was
      clearly detected in the putamen of control and Parkinson's disease patients. A
      modest but significant upregulation of GDNF mRNA levels (Isoform I) was observed
      in the putamen of Parkinson's disease patients with a marked loss of nigral
      neurons. No significant changes were observed for the expression of cRet and
      GFRa1. These data suggest that the extensive loss of dopaminergic neurons in the
      substantia nigra, and concomitant loss of striatal dopamine, may induce
      compensatory changes in the expression of target derived GDNF, but not its
      receptor system.

PMID- 16644103
TI  - Diffusion-weighted MR imaging improves diagnosis of CNS lymphomas. A report of
      four cases with common and uncommon imaging features.
AB  - The frequency of CNS lymphomas is increasing in immunocompetent as well as in
      immunocompromised patients and its incidence accounts for approximately 1-2% of
      all primary cerebral neoplasms. It is a challenge to recognize CNS lymphomas by
      MR imaging as early as possible in order to dispose an optimal therapy. The aim
      of this report is to demonstrate, how diffusion-weighted MR imaging improves the
      accuracy of the differential diagnosis of CNS lymphomas.

PMID- 16644104
TI  - Application of a methylation gene panel by quantitative PCR for lung cancers.
AB  - Detection of lung cancer at early stages could potentially increase survival
      rates. One promising approach is the application of suitable lung cancer-specific
      biomarkers to specimens obtained by non-invasive methods. Thus far, clinically
      useful biomarkers that have high sensitivity have proven elusive. Certain genes,
      which are involved in cellular pathways such as signal transduction, apoptosis,
      cell to cell communication, cell cycles and cytokine signaling are down-regulated
      in cancers and may be considered as potential tumor suppressor genes. Aberrant
      promoter hypermethylation is a major mechanism for silencing tumor suppressor
      genes in many kinds of human cancers. Using quantitative real time PCR, we tested
      11 genes (3-OST-2, RASSF1A, DcR1, DcR2, P16, DAPK, APC, ECAD, HCAD, SOCS1, SOCS3)
      for levels of methylation within their promoter sequences in non-small cell lung
      cancers (NSCLC), adjacent non-malignant lung tissues, in peripheral blood
      mononuclear cells (PBMC) from cancer free patients, in sputum of cancer patients
      and controls. Of all the 11 genes tested 3-OST-2 showed the highest levels of
      promoter methylation in tumors combined with lowest levels of promoter
      methylation in control tissues. 3-OST-2 followed by, RASSF1A showed increased
      levels of methylation with advanced tumor stage (P<0.05). Thus, quantitative
      analysis of 3-OST-2 and RASSF1A methylation appears to be a promising biomarker
      assay for NSCLC and should be further explored in a clinical study. Our
      preliminary data on the analysis of sputum DNA specimens from cancer patients
      further support these observations.

PMID- 16644105
TI  - A conjugate of camptothecin and a somatostatin analog against prostate cancer
      cell invasion via a possible signaling pathway involving PI3K/Akt,
      alphaVbeta3/alphaVbeta5 and MMP-2/-9.
AB  - Camptothecin (CPT) was conjugated to the N-terminal of a somatostatin analog
      (SSA) directly via a carbamate group and a basic N-terminal linking motif, D-Lys
      D-Tyr-Lys-D-Tyr-D-Lys. This new CPT-SSA conjugate termed JF-10-81 was evaluated
      as a receptor-specific delivery system for its anti-invasive and anti-angiogenic
      activities. It was found that, in addition to blocking migration and invasion of
      highly invasive prostate cancer PC-3 cells, this conjugate also inhibited in
      vitro capillary-like tube formation of endothelial cells and in vivo angiogenesis
      in C57B1/6N female mice. JF-10-81 was found to block PC-3 cell attachment to
      various extracellular matrix components, mainly to vitronectin, the ligand of
      cell surface receptors integrin alphaVbeta3 and alphaVbeta5. Additionally, JF-10
      81 reduced expression of integrins alphaVbeta3 and alphaVbeta5 on PC-3 cell
      surfaces, without effects on beta1 or any alphabeta1 heterodimers. This conjugate
      also inactivated phosphorylation of protein kinase B (PKB/Akt), down-regulated
      the expression of latent matrix metalloproteinase (MMP) -2 and MMP-9, but had
      little effect on MMP-3/-10. Meanwhile, membrane type-1 matrix metalloproteinase
      (MT1-MMP) and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) were
      not detectable in PC-3 cells. alphaVbeta3/alphaVbeta5 and MMP-2/-9 are known to
      be highly expressed in many tumor cells and play an important role in tumor
      progression. Our results support that this conjugate could possibly inhibit
      prostate cancer PC-3 cell invasion through a signaling pathway involving
      PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9, and this SSA could be used as an
      efficient vector to deliver CPT or other cytotoxic agents to target sites for
      cancer therapy.

PMID- 16644106
TI  - Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4
      benzoxazin-3-one (DIBOA), two naturally occurring benzoxazinones contained in
      sprouts of Gramineae are potent aneugens in human-derived liver cells (HepG2).
AB  - Benzoxazinoids (BAs) are toxic constituents of sprouts of Gramineae such as
      wheat, maize and rye and are part of the plant defence system against pests. In
      the last years, sprouts have been increasingly consumed as health foods and are
      also used for the production of dietary supplements. In the present study we
      investigated the mutagenic activities of the two most abundant BAs, namely 2,4
      dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4
      benzoxazin-3-one (DIBOA) in the Salmonella/microsome assay and additionally, in
      micronucleus (MN) assay and single cell gel electrophoresis (SCGE) assay in a
      human-derived liver cell line (HepG2). DIBOA caused significant induction of
      his(+) revertants in all three strains in the range between 0.02 and 0.50
      mg/plate; the highest activity was observed in TA100 (fivefold increase over the
      background at the highest dose level). The effect in YG1024 (a derivative of TA98
      with increased acetyltransferase activity) was only slightly higher than the
      effect in the parental strain indicating that acetylation plays no crucial role
      in the activation of this BA. DIMBOA was in general less active and a positive
      result was only seen in the base substitution strain (TA100). Addition of rat
      liver homogenate (S9-mix) led to a significant (ca. twofold) increase of the
      mutagenic activities of both BAs. In SCGE assays with HepG2 cells consistently
      negative results were obtained with both compounds whereas in MN assays
      significant dose dependent effects were observed under similar experimental
      conditions. DIMBOA caused significant effects already at concentrations > or =1
      microM; at the highest dose (20 microM) the MN frequency was sevenfold higher
      than the background level. DIBOA caused weaker effects and was positive at doses
      > or =2.5 microM, the maximal induction (twofold over background) was observed
      with 20 microM. Overall, DIMBOA was ca. 30-fold more active as DIBOA. Subsequent
      experiments with pancentromeric probes showed that >80% of the MN induced at the
      highest doses gave a centromere positive signal indicating that both BAs are
      aneugenic. This is an interesting observation as it is assumed that aneuploidy is
      a key event in cancer induction and at present no other aneugenic plant-derived
      substances of dietary relevance are known.

PMID- 16644107
TI  - Radio-responsive gene therapy for malignant glioma cells without the
      radiosensitive promoter: Caspase-3 gene therapy combined with radiation.
AB  - Caspase-3 plays a critical role as an executioner of apoptosis. The aim of this
      study is to evaluate the potential of the combination of caspase-3 gene therapy
      and radiation treatment. We prepared a plasmid (pCI-CSP3) that contained the
      human caspase-3 gene and the cytomegalovirus promoter. We introduced this plasmid
      into U251 and U87 human glioma cells and subjected the cells to radiation
      treatment. The degree of cell death and apoptosis were evaluated. None of the
      cell lines underwent apoptosis by the overexpression of caspase-3 alone, but the
      degree of cell death and apoptosis were markedly enhanced by the addition of
      radiation treatment. Next, we prepared another plasmid (EGR-CSP3) that contained
      the caspase-3 gene and a radiation-sensitive promoter. Each treatment system
      using either pCI-CSP3 or EGR-CSP3 showed radio response. The treatment system
      using pCI-CSP3 more effectively induced apoptosis than that using EGR-CSP3.
      Caspase-3 gene therapy in combination with radiation treatment has the potential
      to serve as a radio-responsive gene therapy without any radiation-sensitive
      promoter.

PMID- 16644108
TI  - Regulation of MDK expression in human cancer cells modulates sensitivities to
      various anticancer drugs: MDK overexpression confers to a multi-drug resistance.
AB  - MDK is a heparin-binding growth factor associated with cancer development. Here,
      we sought to examine the association of MDK expression with resistance and
      sensitivity to different chemotherapeutic agents. We established stable HeLa cell
      transfectants (HeLa-MDK) and tested for decreased sensitivity to chemotherapeutic
      agents (5-FU, doxorubicin, and cisplatin). In addition, we used siRNA to block
      MDK expression in SNU-638 human gastric cancer cells and examined the
      chemosensitizing effect. HeLa-MDK cells treated with 5-FU, doxorubicin, and
      cisplatin showed a fold increase in the average IC(50) and an increased cell
      survival. siRNA-based knockdown of MDK expression in SNU-638 cells decreased the
      average IC(50) by 18-44% in cells treated with three drugs. Further
      investigations on the molecular mechanism should be clarified, but these results
      indicate that MDK up- and down-regulation appears to be capable of changing the
      chemosensitivities of cancer cells and MDK may have possible importance as a
      candidate therapeutic molecule.

PMID- 16644109
TI  - Docetaxel-induced growth inhibition and apoptosis in androgen independent
      prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3.
AB  - Pre-treatment with high-dose 1alpha,25-dihydroxyvitamin D(3) (1,25-VD) enhanced
      the antitumor activity of docetaxel in the androgen-independent prostate cancer
      cell line, PC-3. The effect manifested as an increasing population of apoptotic
      cells and amount of pro-apoptotic protein, Bax, under combined treatment compared
      with single treatment of either 1,25-VD or docetaxel alone. We further
      demonstrated that pre-treatment with 1,25-VD reduced the expression of multidrug
      resistance-associated protein-1 at both the mRNA and protein levels. This
      suggests pre-treatment with 1,25-VD can potentiate cytotoxicity of docetaxel in
      PC-3 due to 1,25-VD reducing multidrug resistance-associated protein-1
      expression.

PMID- 16644110
TI  - Genetic and epigenetic analysis of the TIMP-3 gene in ovarian cancer.
AB  - Chromosome 22q shows a high frequency of loss of heterozygosity (LOH) in ovarian
      cancers suggesting the existence of one or more important tumor suppressor genes
      (TSGs). The tissue inhibitor of metalloproteinase-3 (TIMP-3) is a plausible TSG
      candidate since it is often encompassed within these regions of LOH. TIMP-3 has
      not previously been investigated for somatic mutations or promoter
      hypermethylation in ovarian cancer. We analyzed 65 ovarian cancers for both
      somatic genetic mutations and TIMP-3 promoter hypermethylation. Screening of all
      coding exons of TIMP-3 did not reveal any somatic genetic mutations and only 1/65
      showed TIMP-3 methylation. Our data indicate that inactivation of TIMP-3 by
      somatic mutation or promoter hypermethylation is rare in ovarian cancer.

PMID- 16644111
TI  - Prevalence of mucosal types of human papillomavirus in skin lesions in north part
      of Iran.
AB  - Human papillomaviruses (HPVs) consist of more than 100 types and are known to be
      associated with numerous malignant tumors, including carcinomas of the mucosal
      and cutaneous epithelium. Non-melanoma skin cancer (NMSC) is the most frequently
      occurring malignancy worldwide in the Caucasian population. Some studies have
      shown that NMSC biopsy specimens harbor cutaneous as well as mucosal human
      papillomavirus, suggesting that mucosal types may play a role in development and
      progression of the tumor in skin. To investigate the presence of mucosal HPV
      types in skin lesions, we performed a retrospective study in which 288 paraffin
      embedded biopsies from benign and malignant skin lesions (NMSC) were collected.
      Using nested PCR with MY09/11 and GP5+/6+ primers mucosal HPVs were detected in
      25.7% of malignant specimens, but just in 0.7% of benign lesions. Direct
      sequencing revealed HPV18 as the most frequent type, which was found in 75% of
      HPV-positive specimens. HPV16 and HPV56 were also detected, 22.3 and 2.7%,
      respectively. These findings suggest that, high-risk mucosal HPV types recently
      identified as significant risk factors for cervical cancer, may also represent a
      risk factor for non-melanoma skin cancer.

PMID- 16644112
TI  - Transient recovery of synaptic transmission is related to rapid energy depletion
      during hypoxia.
AB  - Transient recovery (TR) of evoked synaptic potential during the late stage of
      hypoxic hypoglycemia (HH) insult was investigated in rat hippocampal slices using
      extracellular recording methods. TR was observed in association with a rapid
      deterioration of antidromic population spikes (aPSs) following HH insult. TR was
      not elicited in normoglycemic hypoxia (NH), in which a gradual and delayed
      deterioration of aPSs was noted. TR was not modulated by either Ca(2+)- or PKC
      dependent processes. When a glycolytic inhibitor was added, NH resulted in a
      rapid deterioration of aPSs and prompted appearance of TR. TR was also seen in
      slices using lactate to generate energy via oxidative phosphorylation, when
      hypoxic conditions were subsequently created. Other pharmacological interventions
      that aimed to cause rapid deterioration of aPSs without depleting energy stores
      failed to reproduce TR. The evidence thus suggests that the underlying mechanisms
      of TR appearance during HH insult are highly correlated with rapid energy
      depletion.

PMID- 16644113
TI  - The nicotinic agonist RJR-2403 compensates the impairment of eyeblink
      conditioning produced by the noncompetitive NMDA-receptor antagonist MK-801.
AB  - The classical conditioning of eyelid responses using trace paradigms is a
      hippocampal-related model of associative learning, involving the activation of N
      methyl-D-aspartate (NMDA) receptors. We have evaluated here the effects of NMDA
      receptor blockage with the selective noncompetitive antagonist (5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate
      (dizocilpine, MK-801). Mice were implanted with stimulating electrodes on the
      supraorbitary nerve and with recording electrodes in the ipsilateral orbicularis
      oculi muscle. Animals were conditioned with a trace shock-SHOCK paradigm. MK-801
      injected animals (0.02 mg/kg) seemed unable to acquire this type of associative
      learning task, but the latency and amplitude of their unconditioned eyelid
      responses was not affected by drug administration. The administration of the
      nicotinic agonist (E)-N-methyl-4-(3-pyridinyl)-3-buten-1-amine (RJR-2403; 2
      mg/kg) was able to restore completely the acquisition of the conditioned response
      when administered both before and after MK-801. In vitro recordings of field
      excitatory postsynaptic potentials (fEPSPs) evoked in the hippocampal CA1 area by
      the electrical stimulation of the Schaffer collateral pathway indicates that RJR
      2403 application to the bath enhance the release of glutamate by a presynaptic
      mechanism. These findings reveal that nicotinic acetylcholine receptors enhance
      glutamatergic transmission in hippocampal circuits involved in the acquisition of
      associative learning.

PMID- 16644114
TI  - Effect of acute and chronic administration of caffeine on pain-like behaviors in
      rats with partial sciatic nerve injury.
AB  - Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine
      A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic
      caffeine administration in rats after partial sciatic nerve injury. The hindpaw
      response to mechanical or cold stimulation was assessed following photochemically
      induced sciatic nerve injury which leads to hypersensitivity to these stimuli.
      Caffeine was administered i.p. acutely or in the drinking water chronically. The
      mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose
      dependently alleviated by acute systemic administration of caffeine (10-80
      mg/kg). The effect of caffeine was, however, associated with side effects
      including locomotor stimulation or depression. Chronic oral administration
      (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine
      starting at the time of nerve injury did not significantly affect the development
      of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced
      neuropathic pain state in nerve-injured rats, but only at very high doses. The
      potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have
      been compensated for by an antinociceptive effect of caffeine through antagonism
      of A2A receptors and tolerance development.

PMID- 16644115
TI  - Transplantation of Schwann cells to subarachnoid space induces repair in contused
      rat spinal cord.
AB  - Schwann cell transplantation is well known to induce repair in the injured spinal
      cord which disables millions of injured patients throughout the world. An ideal
      route of delivering the grafted Schwann cells to the spinal cord should neither
      cause more injury nor reinitiate inflammatory events and also provide a favorable
      milieu to the grafted cells. In this study, we have utilized subarachnoid route
      to transplant Schwann cells and evaluated their effects in a contusive model of
      spinal cord injury. Adult rats weighing 100-140 g were experimentally injured by
      crushing the spinal cord with a titanium clip and then divided into four groups
      (Tracing, Control, Medium-treated and Schwann cell-treated). Cultured Schwann
      cells (5x10(4) cells in 5 microl) or medium were injected to the animals of
      corresponding groups via subarachnoid space at the injured site 7 days after
      injury. In tracing group, Schwann cells (labeled with Hoechst) demonstrated their
      presence within spinal cord 7 days after transplantation. Evaluation of locomotor
      performance of animals for 60 days after injury showed that animals treated with
      Schwann cells had significant improvement (P<0.01). Similarly, the axon density
      at the site of injury was significantly higher. The results indicate the efficacy
      of subarachnoid route for the transplantation of Schwann cells in inducing repair
      of the contused spinal cord. We conclude that this route can be useful for the
      transplantation of Schwann cells and offers a hope for the patients suffering
      from spinal cord injury.

PMID- 16644116
TI  - In vitro and in vivo neuroprotection by gamma-glutamylcysteine ethyl ester
      against MPTP: relevance to the role of glutathione in Parkinson's disease.
AB  - Glutathione is an abundant intracellular thiol antioxidant whose levels are
      reduced both in Parkinson's disease itself and in a widely used animal model of
      the disorder, systemic MPTP administration. Previous in vitro work from our
      laboratory has suggested that glutathione depletion may be directly responsible
      for mitochondrial dysfunction, which ultimately leads to dopaminergic cell death
      associated with the disease. Here, we demonstrate the ability of gamma
      glutamylcysteine ethyl ester, a lipid permeable derivative of the major substrate
      for scavenger glutathione synthesis, to counteract glutathione loss and
      neurodegeneration associated with in vitro and in vivo administration of MPTP or
      its derivatives. This data suggests that prevention of glutathione depletion is a
      likely therapeutic target for the disease.

PMID- 16644117
TI  - Differential effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on
      BDNF mRNA expression in rat frontal cortex and hippocampus.
AB  - The serotonergic neurotoxin 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
      produces rapid serotonin (5-HT) depletion in different areas of the forebrain
      after acute administration to rats and other animal species. We previously found
      that 5-HT depletion induced by acute MDMA treatment was transient in the frontal
      cortex, but not in the hippocampus, and recovery of cortical 5-HT levels
      correlated with an induction of CRE-binding activity and increased expression of
      tryptophan-hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis. As
      the brain-derived neurotrophic factor (BDNF) stimulates the growth and sprouting
      of serotonergic neurons, we sought the possible involvement of this neurotrophin
      in the region-specific increase in TPH mRNA expression induced by MDMA. We here
      report that, 24-48 h after acute MDMA treatment, the expression of BDNF in the
      frontal cortex is increased by approximately 33-70%, and the levels of the
      transcription factor phospho-CREB are also increased. In the hippocampus,
      however, a time-dependent decrease in BDNF mRNA expression (maximal decrease of
      approximately 73%) is found in all subfields examined 2-7 days after treatment in
      spite of increased phospho-CREB levels, perhaps as a consequence of
      corticosterone release by the serotonergic neurotoxin. The differential
      regulation of BDNF mRNA expression in the two brain regions examined appears to
      account for the enhanced TPH expression and the recovery of 5-HT levels in the
      frontal cortex, but not in the hippocampus, after neurotoxin treatment.

PMID- 16644118
TI  - Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple
      sclerosis.
AB  - Axonal degeneration in multiple sclerosis (MS) may be caused by mitochondrial
      dysfunction and is associated with decreased levels of N-acetylaspartate (NAA) as
      measured with 1H-magnetic resonance spectroscopy (MRS). Fluoxetine stimulates
      astrocytic glycogenolysis, which serves as an energy source for axons. Eleven
      patients with MS received fluoxetine orally 20 mg a day during the first week,
      and 40 mg a day during the second week. The mean NAA/Creatine ratio in cerebral
      white matter of the MS patients increased from 1.77 at baseline to 1.84 at the
      end of the second week (p=0.007). These findings show evidence for a reversible
      axonal dysfunction in patients with MS and provide a rationale for investigating
      whether fluoxetine has neuroprotective effects in MS.

PMID- 16644119
TI  - Amyloid beta-peptide1-42 alters tight junction protein distribution and
      expression in brain microvessel endothelial cells.
AB  - Alzheimer's disease is characterised by neuronal loss, numerous intraneuronal
      deposits of neurofibrillary tangles, senile plaques, and cerebrovascular amyloid
      deposits. The major component of senile plaques and cerebrovascular deposits is
      the 39-43 amino acid beta-amyloid peptide (Abeta). The effects of Abeta on
      cerebral endothelium and thus the blood-brain barrier remain unclear. Utilising
      endothelial cells isolated from rat cerebral cortex microvessels, we have
      examined effects of Abeta peptides on tight junction protein behaviour. The
      transmembrane tight junction proteins occludin, claudin-1 and claudin-5, as well
      as the cytoplasmic accessory proteins ZO-1 and ZO-2 displayed a continuous
      distribution at cell boundaries. Endothelial cells exposed to Abeta1-42 (20
      microM) for 3 days showed a disrupted plasma membrane pattern of claudin-5 and ZO
      2 with relocation to the cytoplasm. These effects were not seen with Abeta25-35
      or Abeta1-40[Gln22] (Dutch type). Abeta1-42 treatment altered also protein
      expression: occludin was lower at 1st day, claudin-1 increased at all times, and
      ZO-2 increased after 1 day and then decreased. These data suggest that Abeta1-42
      effects on tight junction protein complexes may alter blood-brain barrier
      integrity and contribute to the neuropathological sequelae of Alzheimer's
      disease.

PMID- 16644120
TI  - Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice:
      involvement of endogenous bradykinin.
AB  - Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP)
      SLIGRL-NH2 slowly develops visceral hypersensitivity to i.col. capsaicin in ddY
      mice. Thus, we further analyzed roles of PAR2 in colonic hypersensitivity, using
      the novel potent PAR2AP, 2-furoyl-LIGRL-NH2 and PAR2-knockout (KO) mice. In ddY
      mice, i.col. 2-furoyl-LIGRL-NH2 produced delayed (6 h later) facilitation of
      capsaicin-evoked visceral nociception, an effect being much more potent than
      SLIGRL-NH2. Such effects were mimicked by i.col. trypsin. In wild-type (WT), but
      not PAR2-KO, mice of C57BL/6 background, i.col. PAR2 agonists caused delayed
      facilitation of sensitivity to capsaicin. The PAR2-triggered visceral
      hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140.
      Our data thus provide ultimate evidence for role of PAR2 in colonic
      hypersensitivity, and suggest involvement of the bradykinin-B2 pathway.

PMID- 16644121
TI  - Involvement of mu- and delta-opioid receptors in the antinociceptive effects
      induced by AMPA receptor antagonist in the spinal cord of rats.
AB  - The present study was performed to explore the involvement of opioid receptors in
      the antinociception induced by a-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA) receptor antagonist in rats. The hindpaw withdrawal latency (HWL) to
      noxious thermal and mechanical stimulation was assessed by hot plate test and the
      Randall Selitto Test. Intrathecal injection of 20 nmol of 1,2,3,4-tetrahydro-6
      nitro-2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX) disodium, a competitive AMPA
      receptor antagonist, increased significantly the HWLs to both thermal and
      mechanical stimulation in rats. The increased HWLs induced by NBQX were dose
      dependently attenuated by the opioid receptor antagonist naloxone, while naloxone
      itself had no marked influences on the HWL of rats. Furthermore, the increased
      HWLs induced by NBQX were inhibited by the mu-opioid antagonist beta
      funaltrexamine (beta-FNA) or the delta-opioid antagonist naltrindole, but not by
      the kappa-opioid antagonist nor-binaltorphimine (nor-BNI). The results suggest
      that mu- and delta-opioid receptors, not kappa-opioid receptor, are involved in
      the antinociception induced by AMPA antagonist in the spinal cord of rats.

PMID- 16644122
TI  - A combined effect of the KPNA3 and KPNB3 genes on susceptibility to
      schizophrenia.
AB  - Recent studies suggest that both the KPNB3 gene and the KPNA3 gene in the long
      arm of chromosome 13 (13q) are associated with schizophrenia. Because these two
      genes belong to the same family of karyopherins, their combined effect on illness
      was investigated among 238 Chinese family trios consisting of fathers, mothers
      and affected offspring with schizophrenia. We detected three single nucleotide
      polymorphisms (SNPs), including rs626716 at the KPNB3 locus, and rs3782929 and
      rs3736830 at the KPNA3 locus. The transmission disequilibrium test (TDT) showed
      allelic association for rs626716 (X2=10.77, P=0.001) and for rs3782929 (X2=4.89,
      P=0.027) but not for rs3736830 (X2=0.29, P=0.59). Although the conditional test
      did not show association either for the rs626716-rs3782929 combinations
      (X2=1.329, d.f.=2, P=0.514) or for the rs626716-rs3736830 combinations (X2=0.606,
      d.f.=2, P=0.739), the 1-d.f. test showed association for the rs626716(C)
      rs3782929(G) combination (X2=10.79, P=0.001) and for the rs626716(C)-rs3736830(G)
      combination (X2=8.64, P=0.003). The present work suggests that the combination of
      the KPNA3 gene and the KPNB3 gene may increase a genetic risk for schizophrenia.

PMID- 16644123
TI  - Glycogen content in the cerebral cortex increases with sleep loss in C57BL/6J
      mice.
AB  - We hypothesized that a function of sleep is to replenish brain glycogen stores
      that become depleted while awake. We have previously tested this hypothesis in
      three inbred strains of mice by measuring brain glycogen after a 6h sleep
      deprivation (SD). Unexpectedly, glycogen content in the cerebral cortex did not
      decrease with SD in two of the strains and was even found to increase in mice of
      the C57BL/6J (B6) strain. Manipulations that initially induce glycogenolysis can
      also induce subsequent glycogen synthesis thereby elevating glycogen content
      beyond baseline. It is thus possible that in B6 mice, cortical glycogen content
      decreased early during SD and became elevated later in SD. In the present study,
      we therefore measured changes in brain glycogen over the course of a 6 h SD and
      during recovery sleep in B6 mice. We found no evidence of a decrease at any time
      during the SD, instead, cortical glycogen content monotonically increased with
      time-spent-awake and, when sleep was allowed, started to revert to control
      levels. Such a time-course is opposite to the one predicted by our initial
      hypothesis. These results demonstrate that glycogen synthesis can be achieved
      during prolonged wakefulness to the extent that it outweighs glycogenolysis.
      Maintaining this energy store seems thus not to be functionally related to sleep
      in this strain.

PMID- 16644124
TI  - Kynurenic acid has a dual action on AMPA receptor responses.
AB  - Glutamate is the predominant excitatory neurotransmitter in the central nervous
      system. The receptors that bind glutamate, including N-methyl-D-aspartate (NMDA)
      and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor
      subtypes, are strongly implicated in higher cognitive processes, especially
      learning and memory. Loss of glutamate receptor function impairs the ability to
      acquire and retain information in some patients subsequent to stroke or brain
      injury, and positive allosteric modulators of glutamate receptors can restore
      learning and memory in some of these patients. Here we demonstrate that kynurenic
      acid (KYNA), an endogenous tryptophan metabolite, acts upon heterologous AMPA
      receptors via two distinct mechanisms. Low (nanomolar to micromolar)
      concentrations of KYNA facilitate AMPA receptor responses, whereas high
      (millimolar) concentrations of KYNA competitively antagonize glutamate receptors.
      Low concentrations of KYNA appear to increase current responses through
      allosteric modulation of desensitization of AMPA receptors. These findings
      suggest the possibility that low concentrations of endogenous KYNA acting at AMPA
      receptors may be a positive modulator of excitatory synaptic transmission.

PMID- 16644125
TI  - Forebrain D1 function and sensorimotor gating in rats: effects of D1 blockade,
      frontal lesions and dopamine denervation.
AB  - Prefrontal D1 hypoactivity is implicated in the pathophysiology of schizophrenia,
      and might contribute to sensorimotor gating deficits in schizophrenia patients,
      based on evidence that D1 blockade in the medial prefrontal cortex (MPFC) reduces
      prepulse inhibition of startle (PPI) in animal models. PPI is disrupted by
      systemic and intra-MPFC infusion of the D1 antagonist, SCH23390. We investigated
      the role of the MPFC in the PPI-disruptive effects of systemic SCH23390
      administration, and more generally, in the dopaminergic regulation of PPI. PPI
      was measured in rats after forebrain manipulations, including systemic
      administration of SCH23390, ibotenic acid lesions of the MPFC, and 6OHDA-induced
      dopamine (DA) depletion from MPFC or nucleus accumbens. Systemic SCH23390
      disrupted PPI; these effects were not opposed by ibotenic acid lesions of the
      MPFC. PPI remained intact after MPFC DA depletion, but--as predicted by Bubser
      and Koch [M. Bubser, M. Koch, Prepulse inhibition of the acoustic startle
      response of rats is reduced by 6 hydroxydopamine lesions of the medial prefrontal
      cortex, Psychopharmacology 113 (1994) 487-492]--a reduction in PPI from pre- to
      post-surgery correlated significantly with MPFC DA loss. The effects of systemic
      SCH23390 were not opposed by NAC DA depletion. D1 receptors regulate PPI in rats,
      but this effect does not appear to be mediated either by the MPFC or by increased
      mesolimbic DA activity.

PMID- 16644126
TI  - Ulva conglobata, a marine algae, has neuroprotective and anti-inflammatory
      effects in murine hippocampal and microglial cells.
AB  - It has been reported that inflammatory processes are associated with the
      pathophysiology of Alzheimer's disease (AD), and the treatment of AD using anti
      inflammatory agents slows the progress of AD. Marine algae have been utilized in
      food products as well as in medicine products for a variety of purposes. In this
      study, we investigated the neuroprotective effects of methanol extracts of Ulva
      conglobata (U. conglobata), a marine algae, on glutamate-induced neurotoxicity in
      the murine hippocampal HT22 cell line and the anti-inflammatory effects on
      interferon gamma (IFN-gamma)-induced microglial activation in BV2 cells. U.
      conglobata methanol extracts significantly attenuated the neurotoxicity induced
      by glutamate in HT22 cells and inhibited nitric oxide production induced by IFN
      gamma in BV2 cells. U. conglobata methanol extract treatments were also examined
      and it was found that they almost completely suppressed the expression of the
      proinflammatory enzyme cyclooxygenase 2 (COX-2) and inducible nitric oxide
      synthase (iNOS). These results suggest that U. conglobata possesses therapeutic
      potential for combating neurodegenerative diseases associated with
      neuroinflammation.

PMID- 16644127
TI  - Pain coping and recovery from whiplash: new data on an important problem.

PMID- 16644128
TI  - Parental catastrophizing about their child's pain. The parent version of the Pain
      Catastrophizing Scale (PCS-P): a preliminary validation.
AB  - Numerous studies have found evidence for the role of catastrophizing about pain
      in adjustment to pain in both adults and children. However, the social context
      influencing pain and pain behaviour has been largely ignored. Especially in
      understanding the complexities of childhood pain, family processes may be of
      major importance. In line with the crucial role of pain catastrophizing in
      explaining adjustment and disability in adults and children, this study
      investigates the role of parental catastrophic thinking about their child's pain
      in explaining child disability and parental distress. To study parental
      catastrophizing, a parent version of the Pain Catastrophizing Scale (PCS-P) was
      developed. An oblique three-factor structure emerged to best fit the data in both
      a sample of parents of schoolchildren (N=205) and in a sample of parents of
      children with chronic pain (N=107). Moreover, this three-factor structure was
      found to be invariant across both parent samples. Further, in the clinical
      sample, parents' catastrophic thinking about their child's pain had a significant
      contribution in explaining (a) childhood illness-related parenting stress,
      parental depression and anxiety, and (b) the child's disability and school
      attendance, beyond the child's pain intensity.

PMID- 16644129
TI  - Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity
      to mechanical and cooling stimuli induced by spinal nerve ligation.
AB  - There is compelling evidence for a strong facilitatory drive modulating spinal
      nociceptive transmission. This is in part via serotonergic pathways and
      originates from the rostroventral medulla. We previously demonstrated that
      neuropathic pain is associated with an enhanced descending facilitatory drive
      onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT
      acting at spinal 5-HT3 receptors. Furthermore, depletion of spinal 5-HT has been
      shown to reduce the at-level mechanical allodynia that follows spinal cord
      injury. To further clarify the role and direction of effect of endogenous 5-HT,
      we investigated the effects of depleting spinal 5-HT, via intrathecal injection
      of 5,7di-hydroxytryptamine (5,7DHT), on pain behaviours after spinal nerve
      ligation (SNL). Depletion of spinal 5-HT in normal animals leads to reductions in
      mechanical and thermal evoked responses of deep dorsal horn neurones implying
      that spinal 5-HT has a predominant facilitatory function. After nerve injury, the
      frequency of paw withdrawals to low intensity mechanical and cooling stimulation
      of the ipsilateral hindpaw in the SNL-5,7DHT group was significantly attenuated
      when compared with the SNL-saline group from day seven post-nerve injury. Sham
      5,7DHT and sham-saline animals showed very little response sensitivity on either
      hindpaw. This 5-HT-mediated difference in behaviour was independent of both the
      up-regulation of the NK1 receptor and spinal microglial activation produced by
      nerve injury. These data suggest that supraspinal serotonergic influences under
      these conditions are facilitatory and are implicated in the maintenance of spinal
      cord neuronal events leading to the behavioural hypersensitivity manifested after
      peripheral nerve damage.

PMID- 16644130
TI  - Multiple pathways for noxious information in the human spinal cord.
AB  - To investigate the pathways of noxious information in the spinal cord in humans,
      we recorded cortical potentials following the stimulation of A-delta fibers using
      a YAG laser applied to two cutaneous points on the back at the C7 and Th10 level,
      4cm to the right of the vertebral spinous process. A multiple source analysis
      showed that four sources were activated; the primary somatosensory cortex (SI),
      bilateral parasylvian region (Parasylvian), and cingulate cortex. The activity of
      the cingulate cortex had two components (N2/P2). The mean peak latencies of the
      activities obtained by C7 and Th10 stimulation were 166.9 and 186.0 ms (SI),
      144.3 and 176.8 ms (contralateral Parasylvian), 152.7 and 185.5 ms (ipsilateral
      Parasylvian), 186.2 and 215.8 ms (N2), and 303.0 and 332.3 ms (P2). Estimated
      spinal conduction velocities (CVs) of the respective activities were 16.8, 9.3,
      8.7, 10.1 and 10.7 m/s. CV of SI was significantly faster than the others
      (P<0.05). Therefore, our results suggested that noxious signals were conveyed
      through at least two distinct pathways of the spinal cord probably reaching
      distinct groups of thalamic nuclei. Further studies are required to clarify the
      functional significance of these two pathways.

PMID- 16644131
TI  - Sex differences in adolescent chronic pain and pain-related coping.
AB  - Sex differences exist in pain and the strategies used to cope with pain. Although
      it is has been proposed that such differences become apparent around puberty,
      somewhat surprisingly very little research has specifically investigated sex as a
      moderator of pain within adolescents. The primary aim of the current study was to
      investigate sex differences in pain and coping within a group of 46 male and 115
      female adolescent chronic pain sufferers. All were aged between 11 and 19 years
      and had been referred to the Pain Management Unit at the Royal National Hospital
      for Rheumatic Diseases, United Kingdom. Patients completed a battery of measures
      including pain experiences and a pain coping questionnaire. No sex differences
      were found in pain chronicity, although males and females did differ in self
      reported pain experiences (females reported higher pain). Sex differences were
      also found in coping behaviours. Females used more social support, positive
      statements and internalizing/catastrophizing, whereas males reported engaging in
      more behavioural distraction. Of these strategies internalizing/catastrophizing
      was found to mediate the relationship between sex and pain. This suggests that
      not only do sex differences exist in the pain experiences and pain-coping
      strategies of adolescents with chronic pain, but that
      internalizing/catastrophizing may be an important mechanism in understanding such
      differences. More research examining potential sex differences in children and
      adolescents is recommended.

PMID- 16644132
TI  - Adult attachment, anxiety, and pain self-efficacy as predictors of pain intensity
      and disability.
AB  - Pain self-efficacy and anxiety have each been shown to contribute substantially
      to pain intensity and pain-related disability. Although adult attachment theory
      has been related separately to chronic pain, anxiety, and self-efficacy, it has
      not before been investigated with either pain self-efficacy or anxiety in the
      context of chronic pain. This study investigated the interrelations between these
      aspects of the chronic pain experience and their relative contributions towards
      pain intensity and disability. A clinical sample of 152 chronic pain patients
      participated in this study, completing self-report measures of attachment, self
      efficacy, pain intensity, and disability, prior to attending a multidisciplinary
      pain clinic. Results revealed that fearful and preoccupied (anxious) attachment
      categories were associated with low pain self-efficacy, while high scores on the
      attachment dimension of comfort with closeness were linked with high pain self
      efficacy, particularly for males. Insecure attachment (whether defined in terms
      of categories or dimensions) was related to higher levels of anxiety. Pain self
      efficacy proved a stronger predictor of pain intensity than did anxiety and was a
      stronger predictor of disability than pain intensity or anxiety. In addition,
      comfort with closeness moderated the associations between pain self-efficacy and
      disability, pain self-efficacy and pain intensity, and anxiety and disability.
      Together, these findings support the value of adopting an attachment theoretical
      approach in the context of chronic pain. Treatment considerations and future
      research directions are considered.

PMID- 16644133
TI  - The role of pain coping strategies in prognosis after whiplash injury: passive
      coping predicts slowed recovery.
AB  - Pain coping strategies are associated with pain severity, psychological distress
      and physical functioning in populations with persistent pain. However, there is
      little evidence regarding the relationship between coping styles and recovery
      from recent musculoskeletal injuries. We performed a large, population-based
      prospective cohort study of traffic injuries to assess the relationship between
      pain coping strategies and recovery from whiplash injuries. Subjects were
      initially assessed within 6 weeks of the injury, with structured telephone
      interview follow-up at 6 weeks, and 3, 6, 9 and 12 months post-injury. Coping was
      measured at 6 weeks using the Pain Management Inventory and recovery was assessed
      at each subsequent follow-up period, using a global self-report question.
      Multivariable Cox proportional hazards models showed that early use of passive
      coping strategies was independently associated with slower recovery. Depressive
      symptomatology (CES-D) was an effect modifier of this relationship. Without
      depressive symptomatology, those using high levels of passive coping recovered
      37% slower than those using low levels of passive coping (HRR=0.63; 95% CI 0.44
      0.91). However, in the presence of depressive symptomatology, those using high
      levels of passive coping recovered 75% more slowly than those who coped less
      passively (HRR=0.25; 95% CI 0.17-0.39). In other words, those with depressive
      symptoms but who used few passive coping strategies recovered four times more
      quickly than those with depressive symptoms who used high levels of passive
      coping. Active coping showed no independent association with recovery. These
      findings highlight the importance of early assessment of both coping behaviors
      and depressive symptomatology.

PMID- 16644134
TI  - Response to editorial on Albrecht et al. (2006).

PMID- 16644135
TI  - Posttraumatic stress symptoms and smoking to reduce negative affect: an
      investigation of trauma-exposed daily smokers.
AB  - The present investigation examined the relations among posttraumatic stress
      symptoms and smoking motives. Participants included 100 daily smokers recruited
      from the community and university settings who reported exposure to at least one
      traumatic event that met criterion A for posttraumatic stress disorder.
      Consistent with prediction, higher levels of posttraumatic stress symptoms were
      associated with smoking to reduce negative affect; this relation was observed
      after controlling for variance accounted for by number of cigarettes smoked per
      day and gender. Results are discussed in terms of the implications of smoking to
      regulate affect among daily smokers who have been exposed to traumatic events.

PMID- 16644136
TI  - Disruption in Th1/Th2 immune response in young adult smokers.
AB  - Interferon (IFN)-gamma and IL-10 cytokines, measures of Th1 and Th2 immunity,
      were examined in 20 healthy nonsmokers (12 males, 8 females) and 19 smokers (11
      males, 8 females), aged 19-41 years (23.46+/-0.82 years). Nonsmokers came to the
      laboratory once; smokers came to the laboratory after ad lib smoking and
      following 24-h smoking abstinence. Salivary cotinine and expired CO confirmed
      smoking status. Plasma was collected at the end of each lab session and assayed
      for peripheral IFN-gamma and IL-10 levels. Among smokers, peripheral IFN-gamma,
      IL-10, or IFN-gamma/IL-10 ratio levels did not change in response to 24-h smoking
      abstinence. IFN-gamma levels and IFN-gamma/IL-10 ratios were higher among female
      smokers while smoking and following 24-h abstinence compared to male smokers in
      both conditions and compared to male and female nonsmokers. There was no sex or
      smoking status difference in IL-10 levels. Results suggest that cigarette smoking
      may have at least short-term damaging effects on the body's normal immune
      balance, particularly for women.

PMID- 16644137
TI  - Using the brain P300 response to identify novel phenotypes reflecting genetic
      vulnerability for adolescent substance misuse.
AB  - We used a novel approach to identify candidate alternative phenotypes for
      investigating genetic influence underlying substance use disorders (SUDs) in
      adolescents. The existing literature suggests that P300 amplitude reduction (P3
      AR) observed in brain event-related potentials is associated with risk for SUDs
      generally, not just alcoholism. Using data from a community-based sample of 17
      year-old male and female twins, we fit biometric models to P3 amplitude data to
      show that it is strongly heritable, especially in boys. The extant evidence
      coupled with our findings strongly supports treating P3-AR as an endophenotype
      indexing SUD risk. We then examined a set of 15 potential alternative phenotypes
      (e.g., frequent use of cannabis) to determine whether they were associated with
      P3-AR. The results indicated that almost all of these alternative phenotypes were
      associated with P3-AR, with larger effect sizes observed for boys. Given the
      strong association of these use phenotypes with P3-AR, which is itself an index
      of genetic risk for SUDs, we conclude that these use phenotypes may provide tools
      for finding vulnerability genes in adolescents who have yet to pass through the
      age of risk for SUDs.

PMID- 16644138
TI  - Hormone fatty acid modifications: gram negative bacteria and vertebrates
      demonstrate common structure and function.
AB  - Bacteria are known to regulate diverse physiological processes through a
      mechanism called quorum sensing (QS). Prokaryotes communicate by extracellular
      signalling compounds, i.e. autoinducers (acyl homoserine lactone, AHL of Gram
      negative bacteria) or pheromones (post-translationally modified peptides of Gram
      positive bacteria), which activate genetic pathways when they reach a sufficient
      concentration (QS). A large number of Gram-negative quorum-sensing systems
      studied so far utilize N-acyl homoserine lactones as signal molecules. In
      vertebrates small synthetic molecules called growth hormone secretagogues (GHSs)
      stimulate the release of growth hormone (GH) from the pituitary. GH release is
      stimulated by hypothalamic GH-releasing hormone (GHRH) and ghrelin (endogenous
      ligand of the GHS-receptor, GHS-R). Ghrelin is a 28-amino acid peptide, in which
      the serine-3 (Ser3) is n-octanoylated, and this modification is essential for
      ghrelin's activity. Ghrelin is the first known case of a peptide hormone modified
      by a fatty acid. The major active form of ghrelin is a 28-amino acid peptide with
      octanoylated Ser3; one of the more represented bacterial autoinducers is the N
      Octanoyl-DL-homoserine lactone (C8-HL) molecule. The authors hypothesize that
      Gram-negative bacteria and vertebrates have a functional similarity in the search
      of food and an important structural homology of AHL and ghrelin for the highly
      conserved Serine-acylated motive in both molecules. Our suggestions could help
      one to understand the convergent origin and the biologic meaning of the Serine
      acylated group in these organisms, a biologic meaning very important due to the
      high conservation in two kingdoms which are so different.

PMID- 16644139
TI  - Schizophrenia and cancer risk: can the CCR5-delta 32 chemokine receptor gene
      mutation play a role?

PMID- 16644140
TI  - Statins and tissue mineralization: putative involvement of alkaline phosphatase.
AB  - Many clinical trials have clearly demonstrated the benefit of statins in the
      prevention of coronary heart disease. Although other effects have subsequently
      been described, the so-called pleiotropic effects of statins, there is a tendency
      to relate all those effects, more or less directly, to inhibition of 3-hydroxy-3
      methylglutaryl coenzyme A. Several clinical and laboratory studies show an
      association between statins and increased bone formation and/or density, but no
      clear explanation for that statin effect has emerged. We therefore hypothetized
      that statins may have an effect on alkaline phosphatase activity (ALP), an enzyme
      with an important role in bone mineralization and that may also contribute to
      pathological mineralization in other tissues, such as vascular calcification. Our
      experience with drug effects on ALP lead us to admit the possibility of finding a
      statin with an ALP increasing effect on bone but not on vascular tissue, or with
      a more marked effect upon one of the ALP isoforms or isoenzymes. That information
      would allow the design of clinical trials to confirm the suitability of a
      specific statin to a specific clinical condition.

PMID- 16644141
TI  - Evolutionary neuropathology & congenital mental retardation: environmental cues
      predictive of maternal deprivation influence the fetus to minimize cerebral
      metabolism in order to express bioenergetic thrift.
AB  - This article will propose that humans have an adaptive vulnerability to certain
      forms of mental retardation, specifically, neuropathological disorders that cause
      decreased energy expenditure in the hippocampus and the cerebral cortex. This
      hypothesis will be analyzed in terms of the thrifty phenotype paradigm according
      to which adverse prenatal events can cause differential gene expression resulting
      in a phenotype that is better suited, metabolically, for a deprived environment.
      For example, a malnourished mother has an increased propensity to give birth to
      offspring that feature a "thrifty phenotype" which permits highly efficient
      calorie utilization, increased fat deposition and a sedentary nature. This
      article interprets several prenatal occurrences, including maternal
      malnourishment, low birth weight, multiparity, short birth interval, advanced
      maternal age and maternal stress--which are currently identified by the
      epidemiological literature as risk factors for neuropathology--to be
      environmental cues that communicate to the fetus that, because it will be
      neglected of maternal investment, developing a metabolically conservative brain
      will be the most effective ecological strategy. Success in hunting and foraging
      in mammals, primates and especially humans is known to be dependent on prolonged
      maternal investment. Low levels of maternal care are known to result in low
      survivorship of offspring, largely because the offspring are forced to subsist
      using simple, low-yield foraging strategies. A predictive, adaptive response,
      marked by cerebral hypometabolism, may produce a level of metabolic conservancy
      that mitigates the risks associated with low levels of maternal care. This
      article will suggest that certain, human neuropathological phenotypes would have
      been well suited for an ecological niche that closely resembled the less skill
      intensive niche of our less encephalized, primate ancestors. The forms of
      congenital neuropathology discussed in this article do not cause damage to vital
      homeostatic systems; most simply decrease the size and energy expenditure of the
      cerebral cortex and the hippocampus, the two structures known to show plasticity
      during changes in ecological rigor in vertebrates. Also, many disorders that
      present comorbidly with neuropathology, such as tendency toward obesity,
      decrement in anabolic hormones, hypotonic musculature, up-regulation of the
      hypothalamic-pituitary-adrenal axis, and decreased thyroid output are associated
      with energy conservancy and the thrifty phenotype, further implicating
      neuropathology in an ecological strategy. Determining the relative impact of
      evolutionary causation on neuropathological disease should prove informative for
      medical and gene therapeutic treatment modalities. Furthermore, use of the
      maternal deprivation paradigm presented here may help researchers more precisely
      identify the risk factors that determine cognitive trajectory.

PMID- 16644142
TI  - Nucleotide substitution pattern in rice paralogues: implication for negative
      correlation between the synonymous substitution rate and codon usage bias.
AB  - Understanding the correlation between synonymous substitution rate and GC content
      is essential to decipher the gene evolution. However, it has been controversial
      on their relationship. We analyzed the GC content and synonymous substitution
      rate in 1092 paralogues produced by two large-scale duplication events in the
      rice genome. According to the GC content at the third codon sites (GC3), the
      paralogues were classified into GC3-rich and GC3-poor genes. By referring to
      their outgroup sequences, we inferred the last common ancestor of sister
      paralogues and, consequently, calculated the average synonymous substitution rate
      for two gene classes. The results suggest that average synonymous substitution
      rate is lower in GC3-rich genes than that in GC3-poor genes, indicating that the
      synonymous substitution rate is negatively correlated with GC content in the rice
      genome. Through characterizing the synonymous nucleotide substitution pattern, we
      found a strong synonymous nucleotide substitution frequency bias from AT to GC in
      GC3-rich genes. This indicates possible limitations of commonly used methods
      developed to estimate the synonymous substitution rate. Their estimates might
      produce misleading results on correlation between the synonymous substitution
      rate and GC content.

PMID- 16644143
TI  - Molecular characterization, structure and developmental expression of Megane bHLH
      factor.
AB  - We report here the full-length sequence identification, molecular
      characterization, detailed demarcation expression analysis relevant to
      morphological marker genes and mapping of a bHLH transcription gene, referred to
      as Megane (Mgn). Mgn protein is structurally related to the neurogenic Drosophila
      hairy and Enhancer of split (h/E(spl)) proteins. The unique structural properties
      of Mgn factor in several characteristic residues define the gene as related to
      h/E(spl), but distinguish it from previously identified mammalian members of the
      family. Mgn is a single copy gene on mouse chromosome 8 and encodes a 27kDa
      protein that functions in the nucleus. First expression of Mgn is detected at
      mouse embryonic day 9.5 within the most rostral part of the cephalic flexure of
      the developing midbrain. Later, Mgn expression extends into other alar areas of
      the midbrain and forebrain, developmentally controlled in a regional specific
      pattern.

PMID- 16644144
TI  - Cloning the genes and DNA binding properties of High Mobility Group B1 (HMGB1)
      proteins from the human blood flukes Schistosoma mansoni and Schistosoma
      japonicum.
AB  - The parasitic helminth Schistosoma mansoni contains three HMGB proteins, HMGB1,
      HMGB2 and HMGB3, of primary amino acid sequences highly similar to vertebrate
      proteins. In this report we describe the characterization of the HMGB1 proteins
      and their genes from S. mansoni and Schistosoma japonicum. The deduced amino acid
      sequences of HMGB1 proteins from both schistosome species are identical, and
      comprise 176 residues. The proteins contain the two evolutionarily highly
      conserved HMG-box domains, A and B, exhibiting 60% similarity to mammalian HMGB1.
      Unlike the human HMGB1 which contains an unbroken run of 30 glutamic or aspartic
      residues, the SmHMGB1 or SjHMGB1 proteins possess unusually short acidic C
      terminal tails (5 acidic residues interrupted by 2 serines). Southern
      hybridization and DNA sequencing revealed a single copy HMGB1 gene, composed of 3
      exons and two introns, in S. mansoni. The exon/intron boundaries are identical to
      those of the human HMGB1 gene, with the exception that the second exon of the
      SmHMGB1 gene which is not split into two exons as in the human HMGB1 gene. RNA
      blot analysis revealed that the SmHMGB1 gene is constitutively expressed in
      similar levels both in male and female worms. The single-sized mRNA for SmHMGB1
      is consistent with the size derived from the cDNA. Although DNA binding
      properties of SmHMGB1 (or SjHMGB1) protein seem to be similar to those previously
      reported with human HMGB1, i.e., preferential binding to supercoiled DNA over
      linear DNA, specific recognition of DNA four-way junctions, DNA-induced
      supercoiling in the presence of topoisomerase I, and DNA bending, we have
      observed two important differences relative to those observed with the human
      HMGB1: (i) the inability of the isolated SmHMGB1 domain A to bend DNA (as
      revealed by T4 ligase-mediated circularization assay), and (ii) higher DNA
      supercoiling and bending potential of the SmHMGB1 protein as compared to its
      human counterpart. The latter finding may indicate that the long acidic C-tail of
      human HMGB1 has much stronger repressive role on DNA bending or DNA supercoiling
      by topoisomerase I at physiological ionic strength than the short C-tail of the
      SmHMGB1 protein. Considering the important role of HMGB1 in DNA replication,
      transcription, recombination, and in particularly, the mediation of inflammation
      responses in mammalian cells, further studies on schistosome HMGB proteins may
      provide valuable information related to schistosomiasis, where inflammation plays
      a critical role in this disease.

PMID- 16644145
TI  - Regional differences among the Finns: a Y-chromosomal perspective.
AB  - Twenty-two Y-chromosomal markers, consisting of fourteen biallelic markers
      (YAP/DYS287, M170, M253, P37, M223, 12f2, M9, P43, Tat, 92R7, P36, SRY-1532, M17,
      P25) and eight STRs (DYS19, DYS385a/b, DYS388, DYS389I/II, DYS390, DYS391,
      DYS392, DYS393), were analyzed in 536 unrelated Finnish males from eastern and
      western subpopulations of Finland. The aim of the study was to analyze regional
      differences in genetic variation within the country, and to analyze the
      population history of the Finns. Our results gave further support to the
      existence of a sharp genetic border between eastern and western Finns so far
      observed exclusively in Y-chromosomal variation. Both biallelic haplogroup and
      STR haplotype networks showed bifurcated structures, and similar clustering was
      evident in haplogroup and haplotype frequencies and genetic distances. These
      results suggest that the western and eastern parts of the country have been
      subject to partly different population histories, which is also supported by
      earlier archaeological, historical and genetic data. It seems probable that early
      migrations from Finno-Ugric sources affected the whole country, whereas
      subsequent migrations from Scandinavia had an impact mainly on the western parts
      of the country. The contacts between Finland and neighboring Finno-Ugric,
      Scandinavian and Baltic regions are evident. However, there is no support for
      recent migrations from Siberia and Central Europe. Our results emphasize the
      importance of incorporating Y-chromosomal data to reveal the population
      substructure which is often left undetected in mitochondrial DNA variation. Early
      assumptions of the homogeneity of the isolated Finnish population have now proven
      to be false, which may also have implications for future association studies.

PMID- 16644146
TI  - Identification of cis and trans-acting transcriptional regulators in
      chondroinduced fibroblasts from the pre-phenotypic gene expression profile.
AB  - Cell differentiation is regulated via expression of successive sets of genes. In
      an in vitro model of chondrocyte differentiation, human dermal fibroblasts (hDFs)
      cultured in collagen sponges are induced to express cartilage matrix genes after
      7 days' culture with demineralized bone powder (DBP). A shift in expression of
      many other genes occurs within 3 days, before chondroblast phenotypic genes are
      detectable. In this study, the pre-chondrogenic gene expression profile was used
      as a starting point to derive information on transcriptional regulation of
      chondrocyte differentiation induced by DBP. Putative cis regulatory elements were
      identified by comparing promoter regions from three genes that are highly
      upregulated in chondroinduced hDFs (BIGH3, COL1A2, and FN1) [Zhou, S., Glowacki,
      J., Yates, K.E, 2004. Comparison of TGF-beta/BMP pathways signaled by
      demineralized bone powder and BMP-2 in human dermal fibroblasts. J. Bone Min.
      Res. 19, 1732-1741] and whose products are known to interact in the matrix [Kim,
      J.E., et al., 2002. Molecular properties of wild-type and mutant betaIG-H3
      proteins. Investig. Ophthalmol. Vis. Sci. 43, 656-661]. The effect of DBP on
      nuclear protein binding to cis elements was measured with an array-based assay.
      Nuclear extracts from hDFs cultured in DBP/collagen sponges for 3 days showed
      increased binding to several cis elements belonging to the families that were
      identified by promoter analysis. Of note, those elements represented targets of
      both signal-activated and developmentally regulated transcription factors. Direct
      measurement of mRNAs showed increased gene expression of both types of
      transcription factors in chondroinduced hDFs, including NFKB2 (290% of control),
      RELA (160%), and GATA2 (190%). Moreover, DBP increased gene expression of
      chondrogenic transcription factors SOX9 (160% of control) and RUNX2 (180%).
      Immunoblot analysis showed that DBP increased both expression (200% of control)
      and phosphorylation (300%) of the Creb protein, a transcription factor that is
      downstream of several signal transduction pathways. Inhibition of protein kinase
      A, protein kinase C, or MAP kinase in hDFs cultured in DBP/collagen sponges
      reduced induction of BIGH3 to approximately 50% of control. These results suggest
      that both signal-activated and developmentally controlled transcriptional
      mechanisms contribute to chondroinduction of hDFs by DBP.

PMID- 16644147
TI  - Morbilliviral infection in a pygmy sperm whale (Kogia breviceps) from Taiwanese
      waters.
AB  - Morbilliviral infection was diagnosed in an adult male pygmy sperm whale (Kogia
      breviceps) from southwestern Taiwan on the basis of pathological findings,
      immunohistochemical staining, and reverse transcription-polymerase chain
      reaction. The whale was found alive stranded on the beach and died after 5 days
      of medical care. It was thin and had dozens of nematode in the first stomach. The
      lungs were dark red and heavy. Histopathological examination revealed diffuse,
      moderate bronchointerstitial pneumonia. Intranuclear and intracytoplasmic
      inclusions with occasional syncytial cell formation were noted in the lungs,
      lymph nodes, and spleen. The RNA extracted from lung tissue was subjected to
      morbilliviral gene amplification. After priming with specific oligonucleotides,
      the cDNA covering the phosphoprotein (P) gene was copied and then amplified by
      PCR. The gene fragment amplified from the lung tissue was sequenced. Phylogenetic
      analysis of partial P gene revealed 97.6% sequence identity to the dolphin
      morbillivirus and 90.2% similarity to the pilot whale morbillivirus.
      Morbilliviral antigens were detected in the lungs, lymph nodes, and spleen by
      immunohistochemistry using polyclonal antibody against rinderpest virus. This is
      the first report of morbilliviral infection with genetic evidence in a pygmy
      sperm whale from the Western Pacific Ocean around Taiwan.

PMID- 16644148
TI  - Effect of cysteamine supplementation of in vitro matured bovine oocytes on
      chilling sensitivity and development of embryos.
AB  - In vitro techniques for production of bovine embryos including in vitro oocyte
      maturation (IVM), fertilization (IVF) and culture (IVC) are becoming increasingly
      employed for a variety of research purposes. However, decreased viability
      following cryopreservation by conventional methods has limited commercial
      applications of these technologies. A practical alternative to facilitate
      transport would be to arrest development by chilling without freezing. The
      present research was undertaken to evaluate chilling sensitivity of IVM-IVF
      embryos at different stages of development, and to determine possible beneficial
      effects of cysteamine treatment during IVM, previously shown to enhance embryo
      development in culture, on survival following chilling at different stages.
      Embryos produced by standard IVM-IVF-IVC methods were chilled to 0 degrees C for
      30 min at 2-cell (30-34 h post-insemination, hpi), 8-cell (48-52 hpi) or
      blastocyst (166-170 hpi) stages. Viability after chilling was assessed by IVC
      with development to expanded blastocyst stage determined on days 7 and 8 post
      insemination (pi) and hatching blastocyst stage determined on days 9 and 10 pi.
      Control embryos at the same stages were handled similarly, but without chilling,
      and development during culture similarly assessed. The effect of cysteamine
      supplementation (100 microM) of the IVM medium was determined for both chilled
      and non-chilled (control) embryos. Cysteamine supplementation during IVM had no
      significant effect on oocyte maturation or fertilization, but increased the
      proportions of oocytes developing to blastocyst stage by day 7 (13.7+/-0.9%
      versus 7.2+/-0.9%; P<0.05), total blastocysts (20.5+/-0.9% versus 15.3+/-1.3%;
      P<0.05), and hatching blastocysts (16.8+/-1.6% versus 12.0+/-1.5%; P<0.05). The
      greater survival in terms of hatching (78.6+/-7.0) following chilling of
      blastocysts produced by IVM-IVF of oocytes matured in media supplemented with
      cysteamine offers promise for applications requiring short-term storage to
      facilitate transport of in vitro produced bovine embryos.

PMID- 16644149
TI  - Cryosurvival of bovine blastocysts is enhanced by culture with trans-10 cis-12
      conjugated linoleic acid (10t,12c CLA).
AB  - An excessive lipid content in embryo cells is a consequence of embryo culture in
      the presence of serum which is suggested to be responsible for their high
      susceptibility to cryopreservation. The objective of the present study was to
      examine the effects of supplementing serum-containing culture media with trans-10
      cis-12 conjugated linoleic acid (10t,12c CLA) on embryo lipid accumulation and
      its subsequent cryopreservation. Abattoir-derived oocytes were matured and
      fertilized in vitro (IVF=day 0). On day 1, presumptive zygotes (n=3390) were
      randomly placed in: (I) (MS), granulosa cell monolayer cultured with M199 and 10%
      serum; (II) (SCLA), granulosa cell monolayer cultured with M199, 10% serum and
      100 microM 10t,12c CLA and (III) (SOF), modified synthetic oviduct fluid, where
      embryo culture proceeded for 8 days. Cleavage rates or D7/D8 embryo quality did
      not vary among treatments. D7/D8 embryo production rate was significantly
      (P<0.001) lower in SOF (17.9+/-1.6%) than in groups MS (29.8+/-2.5%) and SCLA
      (27.8+/-2.0%). After cytoplasmic lipid droplets observation under Nomarski
      microscopy, classified embryos were the leanest when cultured in SOF,
      intermediate in SCLA and the fattest in MS (P<0.02). Post-thawing intact
      blastocyst rates where significantly higher in the SCLA group (84.7+/-4.1%) than
      in SOCS (50.3+/-4.8%, P=0.0007) or SOF (65.3+/-6.9%, P=0.03) groups. Post-thawing
      re-expanding rates were significantly lower when embryos were cultured in MS
      (34.7+/-3.7%) than in SCLA (63.7+/-5.3%, P=0.0006) or SOF (49.0+/-4.6%, P=0.04).
      Moreover, re-expanding rates were lower (P=0.05) in SOF than in SCLA cultured
      embryos. These results clearly show that addition of CLA to serum-containing
      media reduced lipid accumulation during in vitro culture and significantly
      improved cryopreservation survival.

PMID- 16644151
TI  - Release characteristics of quinupramine from the ethylene-vinyl acetate matrix.
AB  - An ethylene-vinyl acetate (EVA) matrix containing quinupramine was prepared in an
      attempt to develop a controlled delivery system for quinupramine. Permeation
      studies of quinupramine through the EVA copolymer membrane were carried out using
      a two-chamber diffusion cell. The rate of drug permeation through the EVA
      membrane was proportional to the PEG 400 volume fraction. The release of
      quinupramine from the EVA matrix was examined using a modified Franz diffusion
      cell. A plasticizer was added to prepare the pore structure of the EVA matrix in
      order to increase the rate of drug release. The effects of PEG 400, membrane
      thickness, drug concentration, temperature, and plasticizer on drug release rate
      were investigated. The drug release rate from the EVA matrix increased with
      increasing PEG 400 volume fraction, temperature and drug loading dose. The
      activation energy for drug release was 5.91, 5.39, 4.68 and 4.52 kcal/mol for a
      loading dose of 0.5%, 1%, 1.5%, and 2%, respectively. Among the plasticizers
      used, diethyl phthalate showed the best results. The release of quinupramine from
      the EVA matrix follows a diffusion-controlled model, where the quantity released
      per unit area is proportional to the square root of time. The controlled release
      of quinupramine was achieved using the EVA polymer including a plasticizer.

PMID- 16644150
TI  - In vitro maturation and intracytoplasmic sperm injection of oocytes collected
      from hormonally stimulated common wombats, Vombatus ursinus.
AB  - Porcine FSH/LH stimulation successfully induced development of multiple large
      (>or=4mm) antral follicles in 10 of 11 common wombats. A mean of 5.5 metaphase II
      (MII) oocytes were aspirated from wombats that were stimulated during the
      follicular phase of the oestrous cycle (n=3) or after pouch young removal (n=3).
      Three subadults (n=3) and two anoestrus adults did not produce MII oocytes
      despite pFSH/pLH administration. In vitro maturation of immature oocytes at the
      time of aspiration doubled the number of MII oocytes that could be collected from
      pFSH/pLH stimulated wombats. Immature oocytes with cumulus attached, matured more
      readily to the MII stage than immature oocytes without cumulus. Following
      intracytoplasmic sperm injection (ICSI), approximately 5% of the oocytes that
      were MII at the time of collection cleaved. Approximately 5% of those that were
      matured by in vitro maturation (IVM) formed two polar bodies following ICSI,
      although they not cleave. Parthenogenesis cannot be excluded. This demonstrates
      that assisted reproductive technologies may be applicable to the common wombat.

PMID- 16644152
TI  - Investigation to find a suitable reference material for use as an inverse gas
      chromatography system suitability test.
AB  - The purpose of this study was to find a suitable material for use as a system
      suitability test material for inverse gas chromatography (IGC). The purpose of a
      system check is to measure the variability of the instrument being used rather
      than the material being analysed. Having such a system check for IGC enables a
      basic GMP requirement to be met. IGC results can then be used in regulatory
      submissions to support other already established techniques for characterising
      pharmaceutical materials. Alpha-alumina was chosen because it is inorganic,
      stable at high temperatures, resistant to hydration and is already established as
      a system check material for surface area determination by nitrogen adsorption.
      Two columns (1 and 2) packed from the same reference sample jar of alpha-alumina
      and analysed under the same conditions yielded dispersive surface energies of
      34.8+/-0.8 and 35.3+/-0.8 mJ/m(2), respectively, at 15% RH. Column 1 was analysed
      on a second IGC system, and gave a dispersive surface energy of 34.7+/-0.2
      mJ/m(2). No significant change was evident after 7 months storage under
      laboratory ambient conditions. Analysis of material from a second reference
      sample jar of alpha-alumina produced results not noticeably different to those of
      the first, yielding a dispersive surface energy of 35.3+/-0.1 mJ/m(2). A change
      was seen to occur in the surface properties alpha-alumina when the humidity was
      varied, but the change appeared to be consistent across the two columns reported.
      Based upon the data in this experimental, alpha-alumina appears to be a suitable
      material for use as a system suitability test material for IGC.

PMID- 16644155
TI  - A retrospective study of the spectral probability of spontaneous otoacoustic
      emissions: rise of octave shifted second mode after infancy.
AB  - The recording of otoacoustic emissions (OAEs) is today a widely used tool in
      medical diagnosis. The mechanisms of OAE generation in the cochlea and their
      transmission to the external ear canal, however, are not well understood and a
      matter of long-standing debates. Here, the frequency distribution of 1660
      spontaneous otoacoustic emissions (SOAEs) from three surveys, covering 296 human
      subjects, is analyzed. Neonates show a monomodal distribution with a peak at 4
      kHz, but both children (5-11 y) and adults show an identical bimodal
      distribution, with two peaks in an octave distance (1.5 and 3 kHz). For the
      combined children and adult data, distribution density at the two peak tops is
      2.8 and 2.7 times as high as at the low between them. Mean SOAE amplitudes are
      unrelated to the two peaks, but show a significant narrow-band dip precisely at
      the low in between at 2140 Hz (P<0.008). External ear canal resonance can explain
      the single 4 kHz mode at birth and the 3 kHz mode in children and adults. The
      octave shifted 1.5 kHz mode remains without mechanical explanation. It may
      reflect descending neural influence from central octave band processing. The
      results are relevant for the interpretation of OAE levels in medical diagnosis.

PMID- 16644154
TI  - Analysis of responses to noise in the ventral cochlear nucleus using Wiener
      kernels.
AB  - Responses to noise were recorded in ventral cochlear nucleus (VCN) neurons of
      anesthetized chinchillas and cats, then analyzed using Wiener-kernel theory.
      First-order kernels, which are proportional to reverse-correlation functions, of
      primary-like (PL) and primary-like with notch (PLN) neurons having low
      characteristic frequency (CF) are similar to those obtained in auditory nerve
      fibers (ANFs). Such kernels consist of lightly damped transient oscillations with
      frequency equal to the neuron's CF. The first-order kernel of high-CF PL and PLN
      neurons displays no evidence of tuning to CF. Second-order kernels of the
      aforementioned VCN neuron types also resemble those in the nerve, irrespective of
      CF. In general, first- and second-order Wiener kernels of chopper neurons are
      similar to those obtained in high-CF ANFs. This is likely the consequence of the
      poor phase-locking capabilities to near-CF tones exhibited by chopper neurons. By
      analyzing second-order kernels using singular-value decomposition, it was
      possible to estimate group delays for the entire neuronal population, regardless
      of the neuron's type or CF. This was done by analyzing the highest-ranking
      singular vector (FSV). Amplitude values of FSVs in chopper neurons in the cat are
      substantially larger than in high-spontaneous ANFs.

PMID- 16644153
TI  - Effects of sound level on fMRI activation in human brainstem, thalamic and
      cortical centers.
AB  - The dependence of fMRI activation on sound level was examined throughout the
      auditory pathway of normal human listeners using continuous broadband noise, a
      stimulus widely used in neuroscientific investigations of auditory processing,
      but largely neglected in neuro-imaging. Several specialized techniques were
      combined here for the first time to enhance detection of brainstem activation,
      mitigate scanner noise, and recover temporal resolution lost by the mitigation
      technique. The main finding was increased activation with increasing level in
      cochlear nucleus, superior olive, inferior colliculus, medial geniculate body and
      auditory cortical areas. We suggest that these increases reflect monotonically
      increasing activity in a preponderance of individual auditory neurons responsive
      to broadband noise. While the time-course of activation changed with level, the
      change was subtle and only significant in a part of the cortex. To our knowledge,
      these are the first fMRI data showing the effects of sound level in subcortical
      centers or for a non-tonal, non-speech stimulus at any stage of the pathway. The
      present results add to the body of parametric data in normal human listeners and
      are fundamental to the design of any fMRI experiment employing continuous noise.

PMID- 16644156
TI  - The role of GABAergic inhibition in shaping duration selectivity of bat inferior
      collicular neurons determined with temporally patterned sound trains.
AB  - A previous study has shown that duration selectivity of neurons in the inferior
      colliculus (IC) of the big brown bat, Eptesicus fuscus becomes sharper with
      increasing pulse repetition rate (PRR). The present study examines the role of
      GABAergic inhibition in improving duration selectivity of bat IC neurons with PRR
      by means of iontophoretic application of GABA as well as its antagonist,
      bicuculline. Duration selectivity of IC neurons is studied by plotting the
      duration tuning curves with the number of impulses per pulse against the pulse
      duration. Duration tuning curves of IC neurons are described as band-, short-,
      long- and all-pass in terms of filtering properties to sound duration.
      Bicuculline application produces more pronounced broadening of duration tuning
      curves at high than at low PRR. Conversely, GABA application produces more
      pronounced narrowing of duration tuning curves at low than at high PRR. In either
      case, sharpening of duration selectivity of IC neurons with increasing PRR is
      abolished during drug application. The duration tuning curves of IC neurons
      progressively broadens with recording depth. Broadening of duration tuning curves
      during bicuculline application is more pronounced for neurons at upper than at
      deep IC. This progressive decrease in duration selectivity with recording depth
      is discussed in relation to spatial distribution gradient of GABAA receptors in
      the IC. Possible biological significance of these findings relevant to bat
      echolocation is discussed.

PMID- 16644157
TI  - Effect of interphase gap and pulse duration on electrically evoked potentials is
      correlated with auditory nerve survival.
AB  - We investigated the effect of pulse duration (PD) and interphase-gap (IPG) on the
      electrically-evoked auditory brain stem response (EABR) and viiith nerve compound
      action potential (ECAP) of deafened guinea pigs in order to test the hypothesis
      that the extent of change in these neural responses is affected by the
      histological status of the auditory nerve. Fifteen guinea pigs were deafened by
      co-administration of kanamycin and furosemide. Animals were acutely implanted
      with an 8-band electrode array at 1, 4 or 12 weeks following deafening. EABR and
      ECAP input/output functions were recorded in response to charge balanced biphasic
      current pulses. We determined the change in current required to equalize; (i) the
      EABR amplitude when the duration of the current pulse was doubled (104-208
      micros/phase); and (ii) the EABR and ECAP amplitudes when the IPG was increased
      from 8 to 58 micros using a 104 micros/phase current pulse. Following the
      completion of each experiment the cochleae were examined quantitatively for
      spiral ganglion neuron survival. As expected, the current level required to evoke
      an EABR with equal amplitude was lower when the animal was stimulated with
      current pulses of 208 compared with 104 micros/phase. Moreover, the current level
      required to evoke EABR/ECAPs with equal amplitude was lower when current pulses
      had an IPG of 58 versus 8 micros. Importantly, there was a reduction in the
      magnitude of this effect with greater neural loss; the reduced efficacy of
      changing both PD and IPG on these electrically-evoked potentials was
      statistically correlated with neural survival. These results may provide a tool
      for investigating the contribution of auditory nerve survival to clinical
      performance among cochlear implant subjects.

PMID- 16644158
TI  - Age-related changes in the response properties of cartwheel cells in rat dorsal
      cochlear nucleus.
AB  - The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show
      neurotransmitter and functional age-related changes suggestive of a
      downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory
      circuits implicated in these changes include vertical and D-multipolar cells.
      Cartwheel cells comprise a large additional population of DCN inhibitory neurons.
      Cartwheel cells receive excitatory inputs from granule cell parallel fibers and
      provide a source of glycinergic inhibitory input onto apical dendrites of DCN
      fusiform cells. The present study compared the response properties from young and
      aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit
      recordings from aged cartwheel cells revealed significantly higher thresholds,
      increased spontaneous activity and significantly altered rate-level functions
      characterized by hyperexcitability at higher intensities. Aged cartwheel cells
      showed a significant reduction in off-set suppression. Collectively, these
      findings suggest a loss of tonic and perhaps response inhibition onto aged DCN
      cartwheel neurons. These changes likely reflect a compensatory downregulation of
      synaptic inhibition in response to a loss of excitatory drive from auditory and
      non-auditory excitatory inputs via granule cells. The impact of increased
      excitability of cartwheel cells on DCN output neurons is likely to be complex,
      influenced by loss of glycinergic release and/or subunit receptor changes which
      would only partially off-set age-related loss of inhibition onto the somata and
      basal dendrites of fusiform cells.

PMID- 16644159
TI  - Redistribution of synaptic AMPA receptors at glutamatergic synapses in the dorsal
      cochlear nucleus as an early response to cochlear ablation in rats.
AB  - This study investigated whether unilateral deafferentation of the presynaptic
      neuron is key in the control of morphology and the subunit composition and
      expression of AMPA type glutamate receptors (GluRs) in neurons of the dorsal
      cochlear nucleus (DCN). Data showed that there are morphological changes at the
      postsynaptic sites which precede presynaptic changes at the auditory nerve (AN)
      synaptic ending in response to peripheral damage, in particular that the
      postsynaptic densities (PSD) of the AN on fusiform cells (FC) are thicker after
      denervation. Moreover, GluR2, GluR3 and GluR4 AMPA receptor subunits were
      redistributed, not only at the synapse of FCs receiving direct contact with the
      AN, but also at the glutamatergic synapse of the parallel fibers on FC and on
      cartwheel cells (CwC) which are indirectly innervated by the AN. Interestingly,
      the same synapses in the DCN contralateral to the lesion and with a normal AN
      synaptic input also redistributed AMPA receptor subunits at the synapse in
      respond to deafferentation. In these synapses, there was an increase of
      immunogold labeling for GluR2/3 subunits but not for GluR2 at 2 days after
      deafferentation.

PMID- 16644160
TI  - Correlation index: a new metric to quantify temporal coding.
AB  - The standard procedure to study temporal encoding of sound waveforms in the
      auditory system has been Fourier analysis of responses to periodic stimuli. We
      introduce a new metric--correlation index (CI)--which is based on a simple
      counting of spike coincidences. It can be used for responses to aperiodic stimuli
      and does not require knowledge of the stimulus. Moreover, the basic procedure of
      comparing spiketimes in spiketrains is more physiological than currently used
      methods for temporal analysis. The CI is the peak value of the normalized
      shuffled autocorrelogram (SAC), which provides a quantitative summary of temporal
      structure in the neural response to arbitrary stimuli. We illustrate the CI and
      SACs by comparing temporal coding in the auditory nerve and output fibers of the
      cochlear nucleus.

PMID- 16644161
TI  - Contributions of Aage Moller in the study of the cochlear nucleus.
AB  - At a time when little was known about processing in the auditory system, Aage
      Moller undertook an extensive investigation of the response properties of
      cochlear nucleus (CN) neurons. With an excellent background in physiological
      acoustics and a command of computational techniques he systematically explored
      neural tuning, rate-level functions, and receptive fields of CN neurons using
      microelectrode recordings. He chose to employ more natural stimuli than just pure
      tones and employed a variety of stimuli consisting of tones, clicks, noise,
      amplitude- and frequency-modulated signals to document both intensity and
      temporal response characteristics. The response to noise stimuli was quantified
      using linear systems analysis which was very innovative at that time. By choosing
      to perform the studies in the white rat rather than cat, he provided important
      comparative data on this first center of the central auditory system. Over a span
      of ten years he provided a significant body of observations of CN units
      properties that has rarely been equaled.

PMID- 16644162
TI  - Effect of aqueous bark extract of Garuga pinnata Roxb. in streptozotocin
      nicotinamide induced type-II diabetes mellitus.
AB  - A study was undertaken to evaluate the antihyperglycemic activity of aqueous
      extract of bark of Garuga pinnata Roxb. (Burseraceae). The various parameters
      studied included fasting blood sugar levels, serum lipid levels, liver glycogen
      content, serum insulin level and glycated hemoglobin in diabetic and normal rats.
      Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus.
      Treatment with the extract at two dose levels showed a significant increase in
      the liver glycogen and serum insulin level and a significant decrease in fasting
      blood glucose and glycated hemoglobin levels. The total cholesterol and serum
      triglycerides levels were also significantly reduced and the HDL cholesterol
      levels were significantly increased upon treatment with the extract thus proving
      the potent antidiabetic property of the plant.

PMID- 16644163
TI  - Factor V Leiden mutation, deficiency of antithrombin III and elevation of factor
      VIII in a child with ischemic stroke: a case report.
AB  - A 4-year-old boy was admitted with left hemiplegia. Thrombophilia marker
      examination resulted with factor V Leiden mutation heterozygosity, a deficiency
      of antithrombin III and a high level of factor VIII. Cranial computed tomography
      scan revealed an ischemic infarct in the region of right anterior cerebral
      artery. In the literature, combinations of multiple thrombophilia risk factors
      that trigger cerebral ischemic stroke in children have been emphasized. To our
      knowledge, this is the first child with these combinations of thrombophilia risk
      factors and ischemic stroke to be reported in the literature.

PMID- 16644164
TI  - [Microbial description of bacteriuria in long-term care facilities: a prospective
      study in the French Teaching Hospital of Strasbourg].
AB  - OBJECTIVE: The authors had for aim to assess, the incidence of symptomatic
      bacteriuria and the level of antibiotic resistance in bacteria identified in long
      term care facilities (LTC). DESIGN: Symptomatic bacteriuria cases were
      prospectively collected, during 9 months in the two LTC of the Strasbourg French
      Teaching Hospital (196 beds). RESULTS: One hundred and eleven bacteriuria cases
      were included. They concerned 67 of the 274 residents (cumulative incidence:
      2.07/1,000 patients-day). A gram-negative bacillus was identified in 85% of the
      symptomatic bacteriuria cases, and Escherichia coli in 40%. Sixty percent of the
      identified bacterial strain was resistant to amoxicillin (Amx-R) and 42% to the
      clavulanic acid combination (AmC-R). Third generation cephalosporins (3GC) were
      effective in 90% of Urinary tract infections (UTIs) and fluoroquinolones in 65%
      (Fq). Four bacterias with broad beta-lactamase spectrum were identified (0.04%)
      including 3 Enterobacter aerogenes. No yeast infection was diagnosed. E. coli
      strains were 65% Amx-R and 50% AmC-R. Concerning the Fq-R strains (15%), 50% were
      cotrimoxazole resistant (Stx-R) and 70% Amx-R; 3GC remained effective (82%).
      CONCLUSION: In LTC, multi-drug resistance bacteria are rare and 3GCs seem to be
      the best first line treatment. Nevertheless, Fq-R is increasing (15 vs 8%), and
      attention must be paid to the antibiotic therapy used.

PMID- 16644165
TI  - Drainage pathways in the middle cranial fossa.

PMID- 16644166
TI  - The lollipop sign: a new cross-sectional sign of hepatic epithelioid
      hemangioendothelioma.
AB  - In four cases of hepatic epithelioid hemangioendothelioma (HEHE), multiple liver
      lesions were depicted on enhanced computed tomography (CT) and/or magnetic
      resonance imaging (MRI) scans. A peculiar sign, a hepatic or portal vein
      terminating at or just within the periphery of some of the liver lesions, was
      noted in all four; the images look like a lollipop. Imaging findings of HEHE can
      suggest other diseases, but this sign buttressed by other radiological findings,
      seems to be specific for this entity.

PMID- 16644167
TI  - Right ovarian vein drainage variant: is there a relationship with pelvic varices?
AB  - OBJECTIVE: To correlate right ovarian vein (ROV) variations that drain into the
      right renal vein (RRV) with the presence of pelvic varices. MATERIALS AND
      METHODS: Routine abdominal multidetector-row computed tomography scans of 324
      women were analyzed for the presence and type of ROV variations in this
      retrospective study. The subjects were divided into 2 groups: those with ROV
      variations and those without such variations. The diameters of the subjects' ROV,
      left ovarian vein (LOV), and parauterine veins were measured. Pelvic varices and
      the presence and degree of ovarian vein reflux were noted and compared between
      the 2 groups. The chi2-test and the Pearson correlation test were used for
      statistical analysis. RESULTS: Thirty-two (9.9%) of 324 women studied exhibited
      ROV variant that drained into the right renal vein, and the remaining subjects
      (90.1%) exhibited a normal pattern of ROV drainage that flowed directly into the
      inferior vena cava. Pelvic varices were identified in 59 (18%) of the subjects.
      Reflux was not observed in any patient without pelvic varices. Fifty-seven of 59
      women exhibited ovarian vein reflux. In 56 of those 57 individuals, reflux
      occurred only in the LOV, and in 1 subject, reflux was noted predominantly in the
      ROV. No significant relationship between the presence of an ROV that drained into
      the right renal vein and pelvic varices was noted. CONCLUSION: Although right
      sided pelvic varices associated with right ovarian vein drainage variations are
      rare, anatomic variations of the right ovarian vein are not. This study did not
      find an association between the presence of right ovarian vein and pelvic
      varices.

PMID- 16644168
TI  - Distribution of three genes involved in the PJM1 iron-sequestering system in
      various Vibrio anguillarum serogroups.
AB  - Gene sequences with high homologies to the two genes fatA and fatD, associated
      with the pJM1 virulence plasmid-encoded iron-sequestering system (anguibactin) in
      Vibrio anguillarum serogroup O1 strains, were found in a range of serogroup O2a
      strains and one NT 4 strain that either contained no plasmids or only small-sized
      plasmids. None of these strains contained the angR gene responsible for
      regulation of the anguibactin synthesis. DNA sequences of presumed fatA and fatD
      fragments from one O2a strain and one NT4 strain were identical to each other.
      The fatA sequence of these strains included 35 nucleotide substitutions and 7
      amino acid substitutions out of 555 nucleotides when compared with the fatA
      sequence of the O1 strain 76775. The fatD sequence included 10 nucleotide
      substitutions and 1 amino acid substitution out of 543 nucleotides when compared
      with 76775. The fact that the majority of nucleotide substitutes in the fatA and
      fatD fragments did not result in amino acid substitutes suggest that these
      sequences may to some degree be preserved by selective pressure. The functional
      role of these genes in the O2a serogroup is most likely different from their role
      in the pJM1 system.

PMID- 16644169
TI  - Evaluation of gene expression analysis using RNA-targeted partial genome arrays.
AB  - Highly parallel cDNA targeting microarrays have been established over the last
      years as the quasi-standard for genome wide expression profiling in pro- and
      eukaryotes. Protocols for the direct detection of RNA or aRNA (amplified RNA) are
      currently emerging. This allows to circumvent the bias introduced by enzymatic
      target molecule preparation. To systematically evaluate the extent of non
      specific target binding on oligonucleotide microarrays designed for total RNA
      expression profiling, a model system of 70-mer probes targeting genes involved in
      magnetosome formation (mam genes) of the bacterium Magnetospirillum
      gryphiswaldense was established utilizing wild-type strain MSR-1 and an isogenic
      deletion mutant MSR-1B that lacks all mam genes. An optimized protocol for the
      direct chemical labelling of total cellular RNAs was used. A linear correlation
      between the amount of applied RNA and the mean global background intensity was
      found which enables a simple and unbiased way of normalizing the data. The
      results obtained with the mam deletion mutant MSR-1B revealed a significant
      number of false positive signals, even under optimal hybridization conditions.
      This indicates a high degree of non-specific binding in microarray experiments
      when using longer oligo- or polynucleotides and RNA as target molecule.
      Comparative microarray analysis of an MSR-1B culture and two MSR-1 wild-type
      cultures grown under different conditions was done via a three-colour
      hybridization assay. The additional information provided by the MSR-1B
      transcriptome revealed differential gene expression in the two MSR-1 cultures,
      which was otherwise undetectable.

PMID- 16644170
TI  - Candidatus "Anammoxoglobus propionicus" a new propionate oxidizing species of
      anaerobic ammonium oxidizing bacteria.
AB  - The bacteria that mediate the anaerobic oxidation of ammonium (anammox) are
      detected worldwide in natural and man-made ecosystems, and contribute up to 50%
      to the loss of inorganic nitrogen in the oceans. Two different anammox species
      rarely live in a single habitat, suggesting that each species has a defined but
      yet unknown niche. Here we describe a new anaerobic ammonium oxidizing bacterium
      with a defined niche: the co-oxidation of propionate and ammonium. The new
      anammox species was enriched in a laboratory scale bioreactor in the presence of
      ammonium and propionate. Interestingly, this particular anammox species could out
      compete other anammox bacteria and heterotrophic denitrifiers for the oxidation
      of propionate in the presence of ammonium, nitrite and nitrate. We provisionally
      named the new species Candidatus "Anammoxoglobus propionicus".

PMID- 16644171
TI  - Qualification and application of a surface plasmon resonance-based assay for
      monitoring potential HAHA responses induced after passive administration of a
      humanized anti Lewis-Y antibody.
AB  - A sensitive, surface plasmon resonance (SPR)-based assay monitoring potential
      human-anti-human antibody (HAHA) reactions against the monoclonal antibody (mAb)
      IGN311 is presented. The latter is a fully humanized Lewis-Y carbohydrate
      specific mAb that is currently tested in a passive immune therapy approach in a
      clinical phase I trial. For the SPR experiments a BIACORE 3000 analyzer was used.
      The ligand IGN311 was covalently coupled to the carboxy-methylated dextran matrix
      of a CM5 research grade chip (BIACORE). In the course of a fully nested
      experimental design, a four parameter logistic equation was identified as
      appropriate calibration model ranging from 0.3 microg/mL (lower limit of
      quantitation, LLOQ) to 200 microg/mL (upper limit of quantitation, ULOQ) using an
      anti-idiotypic mAb ('HAHA mimic') as calibrator. The bias ranged from -2.4% to
      5.5% and the intermediate precision expressed as 95% CI revealed values from 5.6%
      to 8.3%. Specificity was evaluated using six human serum matrices from healthy
      donors spiked with calibrator at the limit of quantitation (LOQ) with >80% of
      values being recovered with less than 25% relative error. The qualified assay was
      applied to monitor potentially induced HAHA reactivity in 11 patients from a
      clinical phase I trial with passively administered IGN311. Of the 11 patients,
      one high HAHA responder and several low responders were identified. Protein-G
      depletion experiments with human serum samples revealed that the observed
      response is predominantly caused by IgG binding to the ligand. The
      characteristics of these HAHA responses were all of the so-called 'Type I' which
      is defined by a peak response around day 15 that decreases from this point
      steadily suggesting that some kind of tolerance is established. Therefore, this
      type of HAHA response is regarded as non critical for the patient's safety.

PMID- 16644172
TI  - Application of coulometric electrode array detection to the analysis of
      isoflavonoids and lignans.
AB  - A comprehensive review of the available methods for the analysis of isoflavonoids
      and lignans in biological matrices based on coulometric electrode array detection
      (CEAD) is presented. Different aspects such as sample extraction and purification
      procedures as well as instrumental settings and method validation are discussed.
      Comparisons with other available protocols using different detection techniques
      such as mass spectrometry or immunoassay are also reported to underline the
      versatility and reliability of the detector. Practical notes and tips for
      scientists working with CEAD are also provided.

PMID- 16644173
TI  - Bioavailabilty and pharmacokinetics of four active alkaloids of traditional
      Chinese medicine Yanhuanglian in rats following intravenous and oral
      administration.
AB  - Corydalis saxicola Bunting (Yanhuanglian) is an important component in various
      prescriptions in traditional Chinese medicine. Yanhuanglian has been demonstrated
      to possess many pharmacological activities, including antibacterial, antiviral
      and anticancer activities. The active fractions are dehydrocavidine, coptisine,
      dehydroapocavidine and tetradehydroscoulerine. The purpose of the present study
      was to examine in vivo pharmacokinetics and tissue distribution in rats by using
      high-performance liquid chromatography (HPLC) coupled with tandem mass
      spectrometry. Systemic clearance of the four active alkaloids in plasma was over
      93% of hepatic blood flow, indicating they may be quickly eliminated via hepatic
      clearance. Less than 10% drugs was excreted via urine following intravenous and
      oral administration, suggesting that these four alkaloids may undergo significant
      metabolism in the body or the drug may be excreted via other routes other than
      urine. There was significantly lower excretion of these four alkaloids following
      oral than intravenous administration, suggesting a significant first pass effect
      after oral administration. There appeared to be wide distribution of those four
      alkaloids in rats as demonstrated by the higher apparent volume of distribution.
      Our results have also demonstrated that the four alkaloids can be absorbed
      following oral administration although there were less than 15% of drugs absorbed
      into systemic circulation. In summary, the favorable oral bioavailability
      properties of those four active alkaloids in rats make Yanhuanglian extract worth
      further investigation for improving oral bioavailability.

PMID- 16644174
TI  - LC-UV and LC-MS evaluation of stress degradation behaviour of avizafone.
AB  - It has been known for many years that benzodiazepine compounds effectively
      antagonize seizures induced by organophosphorous nerve agents. In the event of
      poisoning, a combination of three drugs is commonly used: an anticholinergic drug
      (e.g. atropine), an oxime used as cholinesterase reactivator (e.g. pralidoxime or
      HI-6) and an anticonvulsant (i.e. benzodiazepine). Most of anticholinergics and
      oximes are freely soluble in water, whereas many benzodiazepines are not.
      However, a water-soluble prodrug form of diazepam, avizafone, has been adopted by
      French armed forces for the immediate treatment of nerve agent seizure. The
      degradation behaviour of this new drug was investigated under different stress
      degradation conditions (hydrolytic, oxidative, photolytic and thermal) as
      recommended by International Conference on Harmonization. Successful separation
      of the active pharmaceutical ingredient from decomposition products formed under
      stress conditions was achieved using liquid chromatography. The method was
      validated with respect to specificity, linearity, precision and accuracy.

PMID- 16644175
TI  - Enhancing patient participation by training radiation oncologists.
AB  - OBJECTIVE: Several studies have shown that patients' active participation to
      their medical interaction is beneficial for their information processing and
      their quality of life. Unfortunately, cancer patients often act rather passively
      in contact with their oncologists. We investigated whether cancer patients'
      participation in radiation therapy consultations could be enhanced by specific
      communicative behaviours of the radiation oncologists (ROs). METHODS: Eight ROs
      and 160 patients participated; 80 patients in the pre training group and 80
      patients in the post training group. The ROs were trained to use specific
      communicative behaviours that are supposed to encourage patient participation. In
      the training special attention was paid to communicative requirements in the
      first minutes of the consultation. The communicative behaviours of the ROs and
      the cancer patients were measured by the Roter Interaction Analysis System, and
      compared before and after the RO training. RESULTS: From the start throughout the
      entire consultation, patients in the post training group participated more in
      interactions than patients in the pre training group: they discussed more
      psychosocial issues, expressed more concerns and contributed more to decision
      making. CONCLUSION: Cancer patients' participation in the initial radiation
      oncology consultations can be increased by training of ROs. PRACTICE
      IMPLICATIONS: The results suggest that doctors working with cancer patients
      should receive communication training and feedback on a regular base.

PMID- 16644176
TI  - Radiological review of specimen radiographs after breast localisation biopsy is
      not always necessary.
AB  - INTRODUCTION: The use of specimen radiographs to confirm the presence of the
      radiological abnormality in a breast specimen after localisation biopsy is
      standard practice. This study aims to show that a trained surgeon may assess
      breast specimen radiographs with similar efficacy as a radiologist. METHODS: This
      retrospective study assessed all patients who had localisation breast surgery
      using wire or ultrasound (US) techniques between January 2002 and March 2003.
      Histopathological records and mammographic details were recorded from the
      hospital notes. A consultant radiologist and surgeon reviewed the specimen
      radiographs, identifying mammographic abnormalities and assessing margins.
      RESULTS: Localisation surgery was performed on 101 patients with US used to
      localize 68. The median specimen weight was 64g. A malignant diagnosis was made
      in 86 patients. In 23, the histological resection margins were considered to be
      close or involved by tumour and re-excision was performed in eight patients.
      Sixty-one specimen radiographs were reviewed. The radiologist identified every
      mammographic abnormality, and the surgeon identified the lesion in 58. The
      positive predictive value of specimen radiographs to identify histologically
      involved margins was 75 and 74% by the radiologist and the surgeon, respectively.
      Where good radiograph margins were reported in 40 and 35 patients by the
      radiologist and surgeon, respectively, 11 and 7 had histologically involved
      margins. CONCLUSIONS: This study shows that a suitably trained or experienced
      surgeon can assess specimen radiographs effectively without the need for
      intraoperative radiological input although complete histological resection is not
      guaranteed despite specimen radiographs demonstrating clear margins.

PMID- 16644177
TI  - Advanced thyroid carcinoma: an experience of 385 cases.
AB  - AIMS: To report clinical outcomes of a large series of cases with advanced
      thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC
      stages III and IV were selected for the study with thyroid cancer. RESULTS:
      Papillary carcinoma and sclerosing carcinoma have better survival than the
      Hurthle cell and insular types. Lymphatic metastasis does not appear to worsen
      the prognosis. All the tumour forms offer the chance of long survival.
      CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma.
      The combined treatments of surgery, metabolic beam therapy, suppressive hormone
      therapy, radiotherapy and chemotherapy cure a high percentage of patients with
      the tumour at an advanced stage.

PMID- 16644178
TI  - Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing
      RINm5F cells.
AB  - Fatty acids have been shown to cause death of rat and human primary pancreatic
      beta cells and of insulin-producing cell lines. These studies focused mainly on
      saturated and monounsaturated FA such as palmitic, stearic and oleic acids. In
      this study, we have performed a comparison of the toxicity of a wider range of
      FA. The toxicity of different FA to insulin-producing RINm5F cells was assessed
      by flow cytometry measuring loss of plasma membrane integrity and increase in DNA
      fragmentation. Additionally, the FA induced neutral lipid accumulation and the FA
      composition were determined. Palmitic, linoleic, gamma-linolenic, oleic, stearic,
      and eicosapentaenoic acid caused DNA fragmentation of insulin-producing RINm5F
      cells. Loss of membrane integrity was mainly caused by linoleic and gamma
      linolenic acid. There was no correlation between cytotoxicity and the abundance
      of the FA in the cells as determined by HPLC analysis. Taken as whole, the toxic
      effect of the FA on insulin-producing RINm5F cells varied irrespective of the
      chain length and the degree of unsaturation. In these cells PA and LA exhibited
      the highest toxicity, whereas AA was not toxic. In addition, the toxicity of most
      tested FA was inversely related to low NLA, except for AA and EPA. The results of
      this study contribute to the understanding of the role of FA in the impairment of
      pancreatic beta cell function that occurs in type 2 diabetes and obesity.

PMID- 16644179
TI  - The bovine IGF2 gene is differentially methylated in oocyte and sperm DNA.
AB  - The insulin-like growth factor 2 gene (IGF2) encodes an essential growth factor
      and is imprinted in various mammalian species. Differentially methylated regions
      (DMRs) are often located within CpG islands and are critically involved in the
      regulation of monoallelic Igf2 expression in the mouse. Only partial sequence
      information is available for the bovine IGF2 gene and no DMR has currently been
      identified. The goal of this study was to identify a DMR within the bovine IGF2
      gene as a prerequisite for further studies on gene-specific methylation patterns
      during preimplantation development. Here we describe the sequence analysis of a
      CpG-rich DNA fragment from the 5' untranslated region spanning exons and introns
      4 and 5 and the identification of a previously unknown DMR in exon 10 of the
      bovine IGF2 gene. Bisulfite analysis revealed that this DMR is differentially
      methylated in mature oocytes and sperm. The identification of an intragenic DMR
      within a developmentally important gene such as the bovine IGF2 gene provides a
      useful tool to evaluate the methylation patterns of embryos derived in vivo and
      in vitro. Our study is the first report of a differentially methylated region in
      a bovine imprinted gene discovered by the analysis of female and male gametes.

PMID- 16644180
TI  - Bacterial lipopolysaccharide-induced oxidative stress in the impairment of
      steroidogenesis and spermatogenesis in rats.
AB  - Microbial infections, localized as well as systemic, are known to cause
      transitive or permanent male infertility. However, the mechanisms of infection
      induced infertility are largely unknown. Earlier reports showed that
      steroidogenesis and spermatogenesis are affected during bacterial
      lipopolysaccharide (LPS)-induced acute inflammation. The present study used an
      LPS rat model to investigate the role of oxidative stress in spermatogenesis.
      Intraperitoneal administration of bacterial LPS (5mg/kg body weight) to adult
      male albino rats elevated testicular malondialdehyde (MDA) and 4-hydroxy-2
      nonenal (HNE), and decreased the activities of testicular antioxidant enzymes
      such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione
      reductase. The GSH/GSSG ratio also decreased significantly. Time series analysis
      revealed transitory oxidative stress and expression of inflammatory mediators
      such as interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS), and
      cyclooxygenase-2 (COX-2) from 3h to 12h after LPS. Testicular expression of
      steroidogenic acute regulatory (StAR) protein decreased to 24h, in correlation
      with damage to spermatogenesis. These data are consistent with oxidative stress
      as a major causal factor in altered steroidogenesis, spermatogenesis, and perhaps
      male infertility during endotoxin-induced acute inflammation.

PMID- 16644181
TI  - Real-time reverse transcription-multiplex PCR for simultaneous and specific
      detection of rfbE and eae genes of Escherichia coli O157:H7.
AB  - A real-time reverse transcription multiplex polymerase chain reaction (rRT-MPCR)
      was developed for detection of mRNA encoded by rfbE and eae genes of
      enterohemorrhagic Escherichia coli (EHEC) O157:H7. A 129-bp and a 106-bp sequence
      specific to rfbE and eae, respectively, were targeted for reverse transcription,
      amplification, and real-time detection. A single-step RT-PCR kit containing a
      mixture of reverse transcriptases converted mRNA into cDNA, which was
      subsequently amplified by Taq polymerase included in the same kit. The real-time
      detection of amplification products was achieved by incorporating rfbE(O157)- and
      eae(O157:H7)-specific TaqMan probes in rRT-MPCR. The ability of two sets of
      primers and probes for specific detection of rfbE(O157) and eae(O157:H7) was
      initially verified by screening RNA of eight E. coli serotypes possessing
      different O antigens and eae alleles. These two sets of primers and probes were
      also tested in a standard real-time PCR (rPCR) using DNA prepared from several E.
      coli and non-E. coli strains to verify that only rfbE(O157)- and eae(O157:H7)
      specific sequences were amplified and detected. The rRT-MPCR was then evaluated
      for detecting low-level contamination of EHEC O157:H7 in feces. When RNA prepared
      from bovine feces, which were artificially seeded with EHEC O157:H7 cells and
      cultured for five hours, was tested in rRT-MPCR as low as 1cfu/g of feces could
      be detected. The detection range for the two genes in fecal cultures was 5.1 x
      10(-1)-5.1 x 10(4) cfu/g of feces. Thus, the described procedure could be applied
      to rapid detection of very low levels of EHEC O157:H7 using total RNA as a
      template. Since the presence of rfbE(O157)- and eae(O157:H7)-specific mRNA is
      dependent on replicating cells, rRT-MPCR could provide important information
      about the viability of EHEC O157:H7 in feces.

PMID- 16644182
TI  - A multiplexed real-time PCR assay for rapid detection of Chlamydia trachomatis
      and identification of serovar L-2, the major cause of Lymphogranuloma venereum in
      New York.
AB  - Lymphogranuloma venereum (LGV) is caused by a rare form of Chlamydia trachomatis
      that is difficult to diagnose, since culture is not readily available, and since
      other methods are not reliable or lack sensitivity. We report here a rapid,
      sensitive, and specific real-time multiplex polymerase chain reaction (PCR) assay
      capable of detecting C. trachomatis and identifying serovar L-2 in the same
      reaction, directly from rectal swabs. The analytical sensitivity of the assay was
      25 genome copies for C. trachomatis, and 50 genome copies for L-2. The analytical
      specificity was 100%, as demonstrated with a diverse range of C. trachomatis
      serovars and other site-specific bacterial pathogens. With the use of a rapid DNA
      extraction method, a blinded validation of spiked rectal swabs correctly
      identified 30 samples containing C. trachomatis cells, L-2 DNA, or negative
      samples. The multiplexed PCR assay also identified serovar L-2 in 13 of 70 rectal
      swab samples taken from symptomatic patients. Twelve additional samples were
      positive for C. trachomatis only, and omp1 sequencing determined these samples as
      either serovar D, E, G, J, or K. This assay represents the first real-time PCR
      method capable of detecting C. trachomatis DNA, and of simultaneously identifying
      C. trachomatis infection as serovar L-2.

PMID- 16644183
TI  - Comparison of chicken gut colonisation by the pathogens Campylobacter jejuni and
      Clostridium perfringens by real-time quantitative PCR.
AB  - We compared the colonisation of the chicken gut by the two important pathogens
      Campylobacter jejuni (frequent food-borne pathogen) and alpha-toxin gene
      containing Clostridium perfringens (causative agent of necrotic enteritis in
      chickens) using a new high-throughput automated DNA purification method for
      microbial biodiversity analyses. The method gave high reproducibility (standard
      deviation of 1.1 C(T)-values for a universal 16S rDNA real-time PCR), and
      inhibition was observed in only 0.9% of the individual DNA purifications (n =
      753). We analysed 253 randomly collected chicken caecal samples (sampled in 2001
      and 2003) from Norwegian chicken flocks by real-time quantitative PCR. Our
      results showed positive correlation (P = 0.009) in chicken caecal colonisation
      between C. jejuni and Cl. perfringens. We also found that there was a significant
      underrepresentation (P = 0.008) of chickens containing high levels of Cl.
      perfringens and low levels of C. jejuni. This indicates a possible interaction
      between these bacteria. Potential interaction between pathogens and other
      bacteria in the gut will certainly be important research fields in the future. As
      demonstrated here, the development of new tools for high-throughput analyses will
      be of key importance for these studies.

PMID- 16644184
TI  - Anticonvulsant action of allopregnanolone in immature rats.
AB  - Anticonvulsant activity of allopregnanolone, a neurosteroid allosterically
      modulating GABA(A) receptor was tested in a model of motor seizures elicited by
      pentetrazol in immature rats. Rats 7, 12, 18, 25 or 90 days old were pretreated
      with allopregnanolone in doses from 5 to 40 mg/kg i.p. and 15 min later
      pentetrazol was injected subcutaneously in a dose of 100 mg/kg. Rats were
      observed in isolation for 30 min. Allopregnanolone dose-dependently suppressed
      both generalized tonic-clonic and minimal clonic seizures with the highest
      efficacy in 12-day-old rats. Anticonvulsant action was least expressed in adult
      animals. Duration of anticonvulsant action tested after a dose of 20 mg/kg in 12-
      and 90-day-old rats demonstrated markedly longer effects in young rats.
      Allopregnanolone compromised motor performance of rats but duration of this
      unwanted effect in 12-day-old rats was shorter than duration of anticonvulsant
      action. This difference can be important for possible clinical use of
      neurosteroids.

PMID- 16644185
TI  - Facial emotion recognition from moving and static point-light images in
      schizophrenia.
AB  - It is well established that schizophrenia is associated with difficulties
      recognising facial expressions of emotion. It has been suggested that this
      impairment could be specific to moving faces [Archer, J., Hay, D., Young, A.,
      1994. Movement, face processing and schizophrenia: evidence of a differential
      deficit in expression analysis. British Journal of Clinical Psychology, 33, 517
      528]. The current study used point-light images to assess whether people with
      schizophrenia can interpret emotions from isolated patterns of facial movement in
      the absence of featural cues. Emotion recognition from moving and static images
      was assessed using a forced choice design with two sets of three emotions (anger,
      sadness and surprise; disgust, fear and happiness). The schizophrenia group was
      significantly better at recognising the emotions from moving images than static
      images. Although the control group was more accurate overall than the
      schizophrenia group, both groups presented the same characteristic patterns of
      performance across tasks. For example, in terms of which emotions were better
      recognised than others and the types of misidentifications that were made. Hence,
      it is concluded that people with schizophrenia are sensitive to the motion
      patterns which underlie individual expressions of emotion and can use this
      information to accurately recognise emotions.

PMID- 16644186
TI  - Hailey-Hailey disease with affective disorder: report of a case with novel ATP2C1
      gene mutation.

PMID- 16644187
TI  - Rapid pacing of embryoid bodies impairs mitochondrial ATP synthesis by a calcium
      dependent mechanism--a model of in vitro differentiated cardiomyocytes to study
      molecular effects of tachycardia.
AB  - Tachycardia may cause substantial molecular and ultrastructural alterations in
      cardiac tissue. The underlying pathophysiology has not been fully explored. The
      purpose of this study was (I) to validate a three-dimensional in vitro pacing
      model, (II) to examine the effect of rapid pacing on mitochondrial function in
      intact cells, and (III) to evaluate the involvement of L-type-channel-mediated
      calcium influx in alterations of mitochondria in cardiomyocytes during rapid
      pacing. In vitro differentiated cardiomyocytes from P19 cells that formed
      embryoid bodies were paced for 24 h with 0.6 and 2.0 Hz. Pacing at 2.0 Hz
      increased mRNA expression and phosphorylation of ERK1/2 and caused cellular
      hypertrophy, indicated by increased protein/DNA ratio, and oxidative stress
      measured as loss of cellular thiols. Rapid pacing additionally provoked
      structural alterations of mitochondria. All these changes are known to occur in
      vivo during atrial fibrillation. The structural alterations of mitochondria were
      accompanied by limitation of ATP production as evidenced by decreased endogenous
      respiration in combination with decreased ATP levels in intact cells. Inhibition
      of calcium inward current with verapamil protected against hypertrophic response
      and oxidative stress. Verapamil ameliorated morphological changes and dysfunction
      of mitochondria. In conclusion, rapid pacing-dependent changes in calcium inward
      current via L-type channels mediate both oxidative stress and mitochondrial
      dysfunction. The in vitro pacing model presented here reflects changes occurring
      during tachycardia and, thus, allows functional analyses of the signaling
      pathways involved.

PMID- 16644188
TI  - Anti-amyloidogenic effects of antioxidants: implications for the prevention and
      therapeutics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one of the most common dementing disorders and has
      profound medical and social consequences. The initiating molecular event is
      unknown, and its pathophysiology is highly complex. However, free radical injury
      appears to be a fundamental process contributing to the neuronal death seen in
      this disorder, and many studies using surrogate markers of oxidative damage have
      provided evidence supporting this hypothesis. Various compounds with antioxidant
      ability attenuated the oxidative stress induced by amyloid beta-protein (Abeta)
      in studies done in vitro and in vivo. Moreover, various antioxidants have been
      reported to inhibit the formation and extension of beta-amyloid fibrils (fAbeta),
      as well as to destabilize preformed fAbeta in vitro. In cell culture experiments,
      destabilized fAbeta were suggested to be less toxic than intact fAbeta. In
      transgenic mice model studies, some antioxidant compounds reduced plaque burden
      in vivo. In this article, we review the recent advances in the research on the
      antioxidants that inhibit the formation of fAbeta, as well as destabilize
      preformed fAbeta. Although the mechanisms by which these compounds inhibit fAbeta
      formation from Abeta, and destabilize preformed fAbeta are still unclear, they
      could be key molecules for the development of preventives and therapeutics for
      AD.

PMID- 16644189
TI  - Interaction between X-Delta-2 and Hox genes regulates segmentation and patterning
      of the anteroposterior axis.
AB  - In vertebrates, the paraxial mesoderm already exhibits a complex Hox gene pattern
      by the time that segmentation occurs and somites are formed. The anterior
      boundaries of the Hox genes are always maintained at the same somite number,
      suggesting coordination between somite formation and Hox expression. To study
      this interaction, we used morpholinos to knockdown either the somitogenesis gene
      X-Delta-2 or the complete Hox paralogous group 1 (PG1) in Xenopus laevis. When X
      Delta-2 is knocked down, Hox genes from different paralogous groups are
      downregulated from the beginning of their expression at gastrula stages. This
      effect is not via the canonical Notch pathway, as it is independent of the Notch
      effector Su(H). We also reveal for the first time a clear role for Hox genes in
      somitogenesis, as loss of PG1 gene function results in the perturbation of somite
      formation and downregulation of the X-Delta-2 expression in the PSM. This effect
      on X-Delta-2 expression is also observed during neurula stages, before the
      somites are formed. These results show that somitogenesis and patterning of the
      anteroposterior axis are closely linked via a feedback loop involving Hox genes
      and X-Delta-2, suggesting the existence of a coordination mechanism between
      somite formation and anteroposterior patterning. Such a mechanism is likely to be
      functional during gastrulation, before the formation of the first pair of
      somites, as suggested by the early X-Delta-2 regulation of the Hox genes.

PMID- 16644190
TI  - Foot formation in Hydra: a novel gene, anklet, is involved in basal disk
      formation.
AB  - We isolated a novel gene by a differential-display RT-PCR method comparing basal
      disk tissue and peduncle tissue in a species of Hydra, Pelmatohydra robusta, and
      we referred to it as anklet. The putative anklet product has a signal sequence in
      its N-terminus, and it has one MAC/PF domain and one EGF domain. In normal hydra,
      the expression of anklet was restricted in the periphery of the basal disk and
      the lowest region of the peduncle. In foot-regenerating animals, anklet was first
      expressed in the newly differentiated basal disk gland cells at the regenerating
      basal end, and then expression became restricted at the periphery of the
      regenerated basal disk and in the lowest region of the peduncle. This spatially
      specific expression pattern suggested that the product of the anklet gene plays a
      role in basal disk formation. We therefore examined the role played by the
      protein product of the anklet gene by suppressing the transcription level of
      anklet using an RNA-mediated interference (RNAi) method. Suppression of the level
      of expression of the anklet gene led to a decrease in basal disk size in normal
      hydra, and to a delay in basal disk regeneration in foot-amputated animals. These
      results suggested that anklet is involved in the formation and maintenance of the
      basal disk in hydra.

PMID- 16644191
TI  - Reaction of layered sodium disilicate SKS-6 with calcium chloride solution as
      revealed by solid state NMR spectroscopy: exploring the calcium ion extracting
      mechanism of SKS-6.
AB  - Solid-state 1H, 29Si NMR and 23Na MQMAS NMR spectroscopy combined with X-ray
      powder diffraction (XRD) technique was used to study the reaction between layered
      sodium disilicate SKS-6 and calcium chloride solution with different
      concentrations. Based on the experimental results the calcium ion extracting
      mechanism of SKS-6 was demonstrated to be via ion replacement, during which
      calcium ions replace sodium ions and combine with the non-bridging oxygen in SKS
      6 for charge compensation, and simultaneously sodium ions leave the interlayer.
      This ion-replacement process was greatly influenced by the substitution of sodium
      ions by protons as well as the calcium ions concentration. Increasing calcium
      ions concentration favors the replacement of sodium ions by calcium ions, but
      prevents sodium ions from being substituted by protons.

PMID- 16644192
TI  - Purification and characterization of an extracellular, uracil specific
      ribonuclease from a Bizionia species isolated from the marine environment of the
      Sundarbans.
AB  - The first ribonuclease (RNase) from the Cytophaga-Flavobacterium-Bacteroides
      phylum, dominant in the marine environment, and also from the first Bizionia
      species isolated from the tropics was purified and characterized. Extracellular
      RNase production occurred when the culture medium contained 5-7% (w/v) NaCl. The
      53.0 kDa enzyme was purified 29 folds with a recovery of 4% and specific activity
      of 630unit/mg protein. The pH and temperature optima are 6.5 and 35 degrees C,
      respectively and the enzyme retains more than half of its activity (relative to
      optimal assay conditions) after 1h pre-incubation separately with 5% (w/v) NaCl
      or from pH 5.0 to 8.5 or at 50 degrees C. Dithiothreitol and beta-mercaptoethanol
      do not inhibit whereas human placental RNase inhibitor protein halves the RNase
      activity. While Mg(2+), Ba(2+) and Ca(2+) enhanced the enzyme activity, Fe(2+),
      Cu(2+) and Hg(2+) inactivated it. This RNase degrades uracil containing nucleic
      acids only. Our isolate could be a novel renewable source of deoxyribonuclease
      (DNase)--free RNase enzyme.

PMID- 16644193
TI  - Isolation, purification and properties of new restriction endonucleases from
      Bacillus badius and Bacillus lentus.
AB  - We tentatively named two enzymes as BbaI and BleI, which were isolated and
      purified from Gram-positive mesophilic bacteria Bacillus badius 1458 and Bacillus
      lentus 1689 respectively, by ammonium sulphate precipitation, phosphocellulose
      and heparin-sepharose column chromatography. SDS-PAGE protein profiles for BbaI
      and BleI showed denatured molecular weights of 52 and 48 kDa, respectively. BbaI
      hydrolyzed pUC18 DNA into 1900 and 700 bp, pBR322 DNA into two fragments of 2800
      and 1500 bp and Phix174 DNA into 3800 and 1600 bp. BleI hydrolyzed pUC18 DNA into
      1800 and 800 bp, pBR322 DNA into two fragments of 2700 and 1600 bp and Phix174
      DNA into 3700 and 1700 bp. The effects of temperature, ionic strength, pH and
      Mg2+ ion concentrations were studied to demonstrate some biochemical properties
      of BbaI and BleI. Maximum activities of these enzymes were observed at 37 degrees
      C (pH 8.0) with 100 mM NaCl and 10 mM Mg2+ concentrations.

PMID- 16644194
TI  - An outer membrane protein A (ompA) homologue from the photosynthetic purple
      sulfur bacterium Allochromatium vinosum.
AB  - A 991 bp DNA fragment, consisting of a 225 amino acid reading frame homologous to
      outer membrane protein coding ompA gene, was cloned from a purple sulfur
      bacterium Allochromatium vinosum. The homology analysis revealed up to 51%
      similarity to other bacterial species. The absence of branching within
      diazotrophs or other taxonomically related groups shows the structural importance
      of the protein regardless of the metabolism and evolution of the species.

PMID- 16644195
TI  - Identification and over-expression of a thermostable lipase from Geobacillus
      thermoleovorans Toshki in Escherichia coli.
AB  - A newly isolated thermophilic strain producing thermostable lipase was identified
      based on 16S rRNA sequencing, where phylogenetic analysis revealed its closeness
      to Geobacillus thermoleovorans. Thermostable lipase from this bacterium was
      cloned using consensus degenerate PCR primers. For over-expression in Escherichia
      coli, the lipase gene was sub-cloned in pET 15b vector with a strong T7 promotor.
      Lipase activity was approximately 4.5-fold higher than in the wild-type strain.
      The lipase enzyme was thermostable at 60 degrees C and pH 8, whereas a 30%
      residual activity was retained when incubated for 1h at 100 degrees C. Optimum
      lipase expression was obtained in 2 x YT medium after 70min of induction by IPTG.

PMID- 16644196
TI  - No effect of a traditional Chinese medicine, Hochu-ekki-to, on antibody titer
      after influenza vaccination in man: a randomized, placebo-controlled, double
      blind trial.
AB  - BACKGROUND: It was shown that a traditional Chinese medicine, Hochu-ekki-to
      (HET), had adjuvant effects in influenza vaccination in an animal experiment.
      This, however, could not be assessed in a clinical study. METHODS: Thirty-two
      healthy subjects were randomly assigned to two groups (control and HET groups) in
      a double-blind manner. HET subjects (n=17) took 7.5 g of HET/day for two weeks;
      control subjects took the same amount of indistinguishable placebo. Then subjects
      were vaccinated against influenza (H1N1, H3N2 and B/Shandong). Hemagglutinin
      titers and natural killer (NK) activity were measured at weeks 0, 1, 2, 4, and
      12. RESULTS: Antiinfluenza titers against the three viruses were increased
      continuously for the first two weeks and leveled off. However, there were no
      significant differences in any titers between the two groups. NK activity peaked
      at week 2 without any inter-group differences. CONCLUSION: We could not find any
      adjuvant effects of HET in this experimental condition.

PMID- 16644197
TI  - Anticoagulant effects of a Cannabis extract in an obese rat model.
AB  - Blood coagulation studies were conducted to determine the possible anti
      /prothrombotic effect of an organic cannabis extract and the three major
      cannabinoids, THC, CBD and CBN. The in vitro effect of the cannabis extract on
      thrombin activity produced an IC50 value of 9.89 mg/ml, compared to THC at 1.79
      mg/ml. It was also found that the extract, THC and CBN showed considerable
      inhibition of thrombin-induced clot formation in vitro with IC50 values of 600,
      87 and 83 microg/ml for the extract, THC and CBN respectively. In an in vivo
      model used to determine clotting times of lean and obese rats treated with a
      cannabis extract, 50% clotting times were found to be 1.5 and 2 fold greater than
      their respective control groups, supporting the results obtained in the in vitro
      model. The study thus shows that Cannabis sativa and the cannabinoids, THC and
      CBN, display anticoagulant activity and may be useful in the treatment of
      diseases such as type 2 diabetes in which a hypercoagulable state exists.

PMID- 16644198
TI  - Role of amino acids in insulin signaling in adipocytes and their potential to
      decrease insulin resistance of adipose tissue.
AB  - Recently, our knowledge concerning the role of amino acids in signal transduction
      in mammals has greatly improved. This significant advance is mainly due to the
      remarkable discovery that the mammalian target of rapamycin (mTOR) protein
      kinase, known to be activated in response to a large number of hormones, growth
      factors and cytokines, is also under the tight control of branched-chain amino
      acids. Actually, both inputs are necessary to fully activate the mTOR pathway,
      the main function of which is to increase cell size, via the regulation of
      translational processes. However, amino acids are able to modulate other
      biological effects and appear to have unexpected actions, as evidenced by our
      recent work in rat adipocytes. The aim of this review is to summarize novel
      findings on the role of mTOR and amino acids in insulin signaling in adipocytes.
      A possible beneficial impact of the use of amino acids in the treatment of
      insulin resistance is discussed, and hypotheses about the molecular mechanisms
      underlying their effect are proposed.

PMID- 16644199
TI  - Interaction of vitamin E and exercise training on oxidative stress and
      antioxidant enzyme activities in rat skeletal muscles.
AB  - It has been shown that free radicals are increased during intensive exercise. We
      hypothesized that vitamin E (vit E) deficiency, which will increase oxidative
      stress, would augment the training-induced adaptation of antioxidant enzymes.
      This study investigated the interaction effect of vit E and exercise training on
      oxidative stress markers and activities of antioxidant enzymes in red quadriceps
      and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were
      divided into trained vit E-adequate, trained vit E-deficient, untrained vit E
      adequate, and untrained vit E-deficient groups. The two trained groups swam 6
      h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E
      free diet for 8 weeks. Vitamin E-training interaction effect was significant on
      thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX),
      and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group
      showed the highest TBARS and GPX activity and the lowest SOD activity in both
      muscles. A significant vit E effect on glutathione reductase and catalase was
      present in both muscles. Glutathione reductase and catalase activities were
      significantly lower in the two vit E-adequate groups combined than in the two vit
      E-deficient groups combined in both muscles. This study shows that vit E status
      and exercise training have interactive effect on oxidative stress and GPX and SOD
      activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise
      induced elevation in GPX activity while inhibiting exercise-induced SOD activity,
      possibly through elevated oxidative stress.

PMID- 16644200
TI  - Comparison of amperometric biosensors fabricated by palladium sputtering,
      palladium electrodeposition and Nafion/carbon nanotube casting on screen-printed
      carbon electrodes.
AB  - Different strategies, including palladium electrodeposition (Pd(CV)), Pd
      sputtering (Pd(S)) and Nafion-solubilized carbon nanotube casting (Nafion/CNT),
      were used to modify screen-printed carbon electrodes (SPCEs) for the fabrication
      of amperometric enzyme biosensors. The electrochemical properties of the bare and
      modified SPCEs and the optimal conditions for surface modification were
      determined. The electrochemical response of the bare SPCE to H(2)O(2) under the
      potential of 0.3 V could be improved about 100-fold by Pd modification by
      electrodeposition or sputtering. By contrast, the electrochemical response of the
      bare SPCE was enhanced by only about 11-fold by Nafion/CNT casting. Moreover, the
      Pd(CV)-SPCEs exhibited better reproducibility of electrochemical response (a
      relative standard deviation (R.S.D.)<6.0%) than freshly prepared Pd(S)-SPCEs
      (R.S.D.>10%). The glucose biosensor fabricated from Pd-modified electrodes could
      be stored for up to 108 days without loosing significant activity. The Pd(CV)
      SPCE also showed very reliable signal characteristics upon 50 consecutively
      repeated measurements of ascorbic acid. The electrocatalytic detection of the Pd
      SPCE was combined with additional advantages of resistance to surface fouling and
      hence good stability. In conclusion, this study demonstrated that deposition of
      Pd thin film on SPCEs by electrodeposition or sputtering provided superior
      enhancement of electrochemical properties compared to Nafion/CNT-SPCEs. Despite
      their high electrochemical response, Pd(S)-SPCEs required an activation process
      to improve stability and Pd(CV)-SPCEs suffered from poor between electrode
      reproducibility.

PMID- 16644201
TI  - Potential role of CCL27 and CCR10 expression in melanoma progression and immune
      escape.
AB  - Aim of this study was to investigate using immunohistochemistry techniques the
      interrelation between T immunoreactive cells and the expression of CCR10 and its
      ligand CCL27 in 59 cutaneous melanocytic lesions. In malignant melanomas, T
      lymphocyte density was significantly decreased from thin melanomas to
      intermediate and thick ones (P<0.0005). CCR10 expression was found both in benign
      and malignant lesions and it was directly correlated with the Breslow depth
      (P=0.0298) and inversely with T lymphocyte density (P=0.0231). Moreover, cases
      with positive sentinel lymph node tended to have a higher CCR10 expression
      compared to cases with negative sentinel lymph node (P=0.0281). When CCR10 and
      CCL27 expression were evaluated together, CCR10-/CCL27-melanomas tended to have a
      higher mean density of CD3+ and CD8+ lymphocytes. Our results suggest that in
      human melanomas CCR10 and CCL27 may act to increase the ability of neoplastic
      cells to grow, invade tissue, disseminate to lymph nodes and to escape the host
      immune response.

PMID- 16644202
TI  - Thimet oligopeptidase (EC 3.4.24.15) activates CPI-0004Na, an extracellularly
      tumour-activated prodrug of doxorubicin.
AB  - CPI-0004Na is a tetrapeptidic extracellularly tumour-activated prodrug of
      doxorubicin. The tetrapeptide structure ensures blood stability and selective
      cleavage by unidentified peptidase(s) released by tumour cells. The purpose of
      this work was to identify the enzyme responsible for the first rate-limiting step
      of CPI-0004Na activation, initially attributed to a 70 kDa acidic (pI=5.2)
      metallopeptidase active at neutral pH that was subsequently purified from HeLa
      cell homogenates. Two electrophoretic bands were isolated and identified by
      matrix-assisted laser desorption ionisation-time of flight (MALDI-tof) and
      electrospray ionisation-quadrupole-time of flight (ESI-Q-tof) mass spectrometry
      as thimet oligopeptidase (TOP). The identity of the CPI-0004Na activating enzyme
      and TOP was further supported by the similar substrate specificity of the
      purified enzyme and recombinant TOP, by thiol stimulation of CPI-0004Na cleavage
      by cancer cell conditioned media (unique characteristic of TOP) and by the
      inhibition of CPI-0004Na activation by specific inhibitors or
      immunoprecipitation. Although other enzymes can be involved, TOP clearly appears
      to be a likely candidate for extracellular activation of the CPI-0004Na prodrug.

PMID- 16644203
TI  - Strategies to eliminate cancer stem cells: clinical implications.
AB  - Over the past two decades, major advances in our understanding of cancer have
      translated into only modest increments in survival for the majority of cancer
      patients. Recent data suggesting cancers arise from rare self-renewing stem cells
      that are biologically distinct from their more numerous differentiated progeny
      may explain this paradox. Current anticancer therapies have been developed to
      decrease the bulk of the tumour mass (i.e. the differentiated cancer cells).
      Although treatments directed against the bulk of the cancer may produce dramatic
      responses, they are unlikely to result in long-term remissions if the rare cancer
      stem cells are also not targeted. Conversely, treatments that selectively attack
      cancer stem cells will not immediately eliminate the differentiated cancer cells,
      and might therefore be prematurely abandoned if clinical activity is judged
      solely by traditional response criteria that reflect changes in the bulk of the
      tumour. Re-examining both our pre-clinical and clinical drug development
      paradigms to include the cancer stem cell concept has the potential to
      revolutionize the treatment of many cancers.

PMID- 16644204
TI  - BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated
      risks to relatives.
AB  - Pathological mutations in BRCA1, BRCA2 and TP53 are associated with an increased
      risk of breast cancer. This study evaluated mutation frequency of these genes in
      early-onset breast cancer patients, and correlated this with family history and
      determined relative risks to family members. Patients with breast adenocarcinoma
      diagnosed 30 years were ascertained between 1980 and 1997. Family history was
      established and mutation screening of BRCA1, BRCA2 and TP53 genes was performed.
      Estimates of penetrance and relative risk were undertaken. DNA was obtained from
      100/139 women. 17/36 familial cases had a BRCA1, BRCA2 or TP53 mutation. Of 64
      non-familial cases, one BRCA2, two BRCA1 and two TP53 mutations were detected.
      Penetrance estimates (by age 70) for breast cancer were 84% for BRCA1 mutations
      and 91% for BRCA2 mutations and for ovarian cancer, 60% and 26%, respectively.
      Relative risks associated with mutations were consistent with previous studies.
      BRCA1 and BRCA2 mutations in patients with breast cancer 30 years are predicted
      strongly by family history. The majority of families with ovarian cancer were due
      to mutations in BRCA1/2 whereas these mutations only accounted for 30-50% of the
      excess breast cancers.

PMID- 16644205
TI  - Profiling cancer stem cells using protein array technology.
AB  - Since cancer cells and somatic stem cells share the biological characteristics of
      self-renewal and proliferation, it has been suggested that the principles of stem
      cell biology can be applied to improve our understanding of cancer biology.
      Recent studies have shown that the majority of cancers appear to originate from a
      small subset of cells that have the ability of self-renewal and to proliferate,
      namely 'cancer stem cells'. The isolation of cancer stem cells has been
      demonstrated using cell surface markers in haematopoietic and non-haematopoietic
      malignancies. Advances in protein array technologies have enabled the use of
      minuscule amounts of biological materials to profile these cells at the molecular
      level. Using a combination of protein arrays and cancer stem cell isolation
      techniques, a higher resolution molecular profiling can be performed, which might
      improve therapies targeting the cancer stem cells.

PMID- 16644206
TI  - Stem cell properties and epithelial malignancies.
AB  - The growth and repair of normal tissues depends on a small sub-population of
      cells termed somatic stem cells whose primary characteristic is an ability for
      indefinite self-renewal. Epithelial stem cells divide to produce cells, termed
      transient amplifying cells, that undergo a few rounds of more rapid division
      before they terminally differentiate. Evidence that the growth of tumours, as for
      normal tissues, is ultimately dependent on a subpopulation of the proliferatively
      competent cells was first shown for leukaemias by isolation of small sub
      populations of phenotypically distinct 'tumour-initiating cells'. Differing cell
      surface phenotypes also prospectively identify tumour-initiating sub-populations
      in solid tumours. Even cell lines derived from tumours retain hierarchical stem
      cell patterns demonstrable as differing clonogenic abilities related to cellular
      properties such as size, adhesiveness, dye exclusion, and patterns of gene
      expression. Malignant stem cells appear to form the primary targets of therapy,
      but how differences between malignant stem and other cells affect therapeutic
      responses remains unclear. However, transplantation methods exist for their
      analysis and the in vitro persistence of stem cell patterns may provide systems
      for developing new therapeutic approaches.

PMID- 16644207
TI  - Telomeres and telomerase in cancer stem cells.
AB  - Alterations in telomere dynamics both suppress and facilitate malignant
      transformation by regulating genomic stability and cell lifespan. Checkpoints
      induced by telomere dysfunction play a major role in tumour suppression, whereas
      telomere shortening contributes to the initiation of cancer by inducing
      chromosomal instability. Since stem cells are exposed to various tumourigenic
      agents and stresses throughout their lifetime, the ageing stem cell is a major
      target of malignant transformation. This review summarises our knowledge of
      telomere length and telomerase activity in stem cells during ageing and
      carcinogenesis.

PMID- 16644208
TI  - Intentional and non-intentional non-adherence to medication amongst breast cancer
      patients.
AB  - This study aimed to investigate the prevalence of and factors associated with non
      adherence to medication amongst a sample of breast cancer patients. 131 women
      with stable disease were interviewed and completed standardised psychological
      measures. 55% of women reported non-adherence to medication frequently or
      occasionally, with younger women and those who disliked taking their medication
      being significantly less adherent (P = 0.015, P = 0.001). Women who deliberately
      omitted taking their tablets occasionally or frequently had significantly lower
      scores, indicative of a weaker influence, on 'internal' and 'powerful others'
      dimensions of health locus of control (P = 0.032, P = 0.009). Despite a life
      threatening diagnosis, patients may not adhere to medication representing a
      potential missed opportunity for health gain and waste of resources. Furthermore,
      interpretation of clinical trial data may be misleading without adherence
      information. More research is needed to identify those at risk for non-adherence.
      If other routes of administration are available these options should be discussed
      with patients to maximise efficacy of therapy.

PMID- 16644209
TI  - Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci.
AB  - Previous in vitro experiments showed that both, Taenia crassiceps and Taenia
      solium cysticerci have the ability to metabolize exogenous androstenedione to
      testosterone. Here we evaluate on the capacity of both cysticerci to synthesize
      several sex steroid hormones, using different hormonal precursors. Experiments
      using thin layer chromatography (TLC) showed that both cysticerci were able to
      produce (3)H-hydroxyprogesterone, (3)H-androstenedione and (3)H-testosterone when
      (3)H-progesterone was used as the precursor. They also synthesized (3)H
      androstenediol and (3)H-testosterone when (3)H-dehydroepiandrosterone was the
      precursor. In addition, both cysticerci interconverted (3)H-estradiol and (3)H
      estrone. These results, strongly suggest the presence and activity of the Delta4
      and Delta5 steroid pathway enzymes, 3beta-hydroxysteroid dehydrogenase/Delta(5-4)
      isomerase-like enzyme (3beta-HSD), that converts androstenediol into
      testosterone; and the 17beta-hydroxysteroid dehydrogenase that interconverts
      estradiol and estrone, in both types of cysticerci.

PMID- 16644210
TI  - Effect of organic and metal ion concentration on the simultaneous biological
      removal of NH4+ and NO3- under anaerobic condition.
AB  - A bacterial strain of Pseudomonas aeruginosa AE-1-3, isolated from soil was used
      to remove NH4+ and NO3- simultaneously in an anaerobic environment containing
      0.1% NH4NO3 and 3% glucose in the medium. After preliminary screening, eight
      isolates were obtained, which were evaluated for their potential to decompose
      NH4+ and NO3-. Each experimental investigation was carried out for 15 days under
      controlled laboratory conditions by varying the concentrations of glucose (0-3%).
      The bacterial strain, AE-1-3 showed 100% removal of both NH4+ and NO3-. The
      effect of metal ions in combinations of Cu2+, Zn2+, Sn2+ were also studied to
      ascertain the performance. The results revealed that NO3- could be removed
      completely in 9 days at 3 microM concentrations of the three metal ions, while
      33% of NH4+ remained in 0.1% NH4NO3 medium with 0.5% glucose in the absence of
      these three ions.

PMID- 16644211
TI  - Isolation and characterization of Cr(VI) reducing Cellulomonas spp. from
      subsurface soils: implications for long-term chromate reduction.
AB  - Microbial enrichments from Cr(VI) contaminated and uncontaminated US Department
      of Energy Hanford Site sediments produced Cr(VI) reducing consortia when grown in
      the presence of Cr(VI) with acetate, D-xylose or glycerol as a carbon and energy
      source. Eight of the nine isolates from the consortia were Gram positive and four
      of these were identified by 16S rRNA sequence homology and membrane fatty acid
      composition as belonging to the genus Cellulomonas. Two strains, ES6 and WS01,
      were further examined for their ability to reduce Cr(VI) under growth and non
      growth conditions. During fermentative growth on D-xylose, ES6 and WS01 decreased
      aqueous Cr(VI) concentrations from 0.04 mM Cr(VI) to below the detection limit
      (0.002 mM Cr(VI)) in less than three days and retained their ability to reduce
      Cr(VI) even after four months of incubation. Washed ES6 and WS01 cells also
      reduced Cr(VI) under non-growth conditions for over four months, both with and
      without the presence of an exogenous electron donor. K-edge XANES spectroscopy
      confirmed the reduction of Cr(VI) to Cr(III). The ability to reduce Cr(VI) after
      growth had stopped and in the absence of an external electron donor, suggests
      that stimulation of these types of organisms may lead to effective long-term, in
      situ passive reactive barriers for Cr(VI) removal. Our results indicate that
      Cr(VI) reduction by indigenous Cellulomonas spp. may be a potential method of in
      situ bioremediation of Cr(VI) contaminated sediment and groundwater.

PMID- 16644212
TI  - Antidyslipidemic activity of furano-flavonoids isolated from Indigofera
      tinctoria.
AB  - Flavonoids appear to play a major role in reducing the risk of cardiovascular
      diseases by decreasing the blood lipid levels. In continuation of our drug
      discovery program on antidyslipidemic agents we have isolated three furano
      flavones 1-3 and a rare flavonol glycoside 4 from the aerial parts of Indigofera
      tinctoria. Our results disclose that the treatment with diastereomeric flavonoid
      mixture 1 and 2 (80:20) significantly decreased the plasma triglycerides (TG) by
      60%, total cholesterol (TC) 19%, glycerol (Gly) 13%, and free fatty acid (FFA)
      25% accompanied with increase in high density lipoproteins-cholesterol (HDL-C) by
      8% and HDL-C/TC ratio 36% in high fat diet (HFD) fed dyslipidemic hamsters at the
      dose of 50 mg/kg body weight. The flavonoid 3 has exhibited moderate
      antidyslipidemic activity.

PMID- 16644213
TI  - Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-acyl aromatic
      alpha-amino acids.
AB  - A series of lysine sulfonamide analogues bearing Nepsilon-acyl aromatic amino
      acids were synthesized using an efficient synthetic route. Evaluation of these
      novel protease inhibitors revealed compounds with high potency against wild-type
      and multiple-protease inhibitor-resistant HIV viruses.

PMID- 16644214
TI  - DNA sequence recognition by an imidazole-containing isopropyl-substituted
      thiazole polyamide (thiazotropsin B).
AB  - We have used DNA footprinting and fluorescence melting experiments to study the
      sequence specific binding of an imidazole-containing isopropyl-substituted
      thiazole polyamide (thiazotropsin B) to DNA. While the parent compound
      (thiazotropsin A) binds to the hexanucleotide sequence ACTAGT, changing one of
      the N-methylpyrrole groups to N-methylimidazole changes the preferred binding
      sequence to (A/T)CGCG(T/A). Experiments with DNA fragments that contain variants
      of this sequence suggest that the ligand can also bind, with lower affinity, to
      sequences which differ from this by 1bp in any position.

PMID- 16644215
TI  - Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase
      inhibitors.
AB  - Using a scaleable, directed library approach based on orthogonally protected
      advanced intermediates, we have prepared a series of potent keto-1,2,4
      oxadiazoles designed to explore the P(2) binding pocket of human mast cell
      tryptase, while building in a high degree of selectivity over human trypsin and
      other serine proteases.

PMID- 16644216
TI  - Synthesis and structure-activity studies of antibacterial oxazolidinones
      containing dihydrothiopyran or dihydrothiazine C-rings.
AB  - A new series of antimicrobial oxazolidinones bearing unsaturated heterocyclic C
      rings is described. Dihydrothiopyran derivatives were prepared from the saturated
      tetrahydrothiopyran sulfoxides via a Pummerer-rearrangement/elimination sequence.
      Two new synthetic approaches to the dihydrothiazine ring system were explored,
      the first involving a novel trifluoroacetylative-detrifluoroacetylative Pummerer
      type reaction sequence and the second involving direct dehydrogenation of
      tetrahydrothiopyran S,S-dioxide intermediates. Final analogs such as 4 and 13
      represent oxidized congeners of recent pre-clinical and clinical oxazolidinones.

PMID- 16644217
TI  - Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as
      inhibitors of the fatty acid transporter FATP4.
AB  - Several potent, cell permeable 4-aryl-dihydropyrimidinones have been identified
      as inhibitors of FATP4. Lipophilic ester substituents at the 5-position and
      substitution at the para-position (optimal groups being -NO(2) and CF(3)) of the
      4-aryl group led to active compounds. In two cases racemates were resolved and
      the S enantiomers shown to have higher potencies.

PMID- 16644218
TI  - Heteroaryl substituted bis-trifluoromethyl carbinols as malonyl-CoA decarboxylase
      inhibitors.
AB  - A series of heteroaryl-substituted bis-trifluoromethyl carbinols were prepared
      and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Some thiazole-based
      derivatives showed potent in vitro MCD inhibitory activities and significantly
      increased glucose oxidation rates in isolated working rat hearts.

PMID- 16644219
TI  - Synthesis and antibacterial activity of new fluoroquinolones containing a
      substituted N-(phenethyl)piperazine moiety.
AB  - N-(Phenethyl)piperazinyl quinolone derivatives that bear a methoxyimino
      substituent have been synthesized and evaluated for antimicrobial activity
      against Gram-positive and Gram-negative microorganisms. In addition, to define
      structure-activity relationships, ciprofloxacin derivatives containing 2-oxo-2
      phenylethyl or 2-hydroxyimino-2-phenylethyl moieties at N-4 position of
      piperazine ring were prepared and tested. Ciprofloxacin derivatives, containing a
      N-(chloro-substituted phenethyl) residue, showed in vitro Gram-positive and Gram
      negative activity generally comparable or superior to that of reference
      quinolones.

PMID- 16644220
TI  - Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3.
AB  - In an effort to identify new protein kinase inhibitors with increased potency and
      selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4
      f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B,
      CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the
      micromolar range. Molecular modeling studies suggest that the most selective GSK
      3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond
      interaction with Val135 and target the specific hydrophobic backpocket of the
      enzyme.

PMID- 16644221
TI  - Discovery and SAR of oxindole-pyridine-based protein kinase B/Akt inhibitors for
      treating cancers.
AB  - We describe a series of potent and selective oxindole-pyridine-based protein
      kinase B/Akt inhibitors. The most potent compound 11n in this series demonstrated
      an IC(50) of 0.17nM against Akt1 and more than 100-fold selectivity over other
      Akt isozymes. The selectivity against other protein kinases was highly dependent
      on the C-3 substitutions at the oxindole scaffold, with unsubstituted 9e or 3
      furan-2-ylmethylene (11n) more selective and 3-(1H-pyrrol-2-yl)methylene (11f) or
      3-(1H-imidazol-2-yl)methylene (11k) less selective. In a mouse xenograft model,
      9d, 11f, and 11n inhibited tumor growth but with accompanying toxicity.

PMID- 16644222
TI  - Microwave-enhanced nucleophilic fluorination in the synthesis of fluoropyridyl
      derivatives of [3,2-c]pyrazolo-corticosteroids, potential glucocorticoid receptor
      mediated imaging agents.
AB  - Fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids have high affinity
      for the glucocorticoid receptor (GR) and are highly active glucocorticoids. They
      are thus considered to be excellent candidates for PET imaging of GR containing
      tissues when labeled with fluorine-18 (t(1/2)=110 min). Previously reported
      syntheses of these fluorinated glucocorticoids were accomplished by conventional
      thermal nucleophilic halogen exchange reactions with chloropyridyl precursors.
      These reactions were found to proceed at rates too slow for feasible application
      to radiosynthesis using [(18)F]fluoride. We have applied microwave-heating
      methods to these reactions and found that significant rate enhancements can be
      realized. Kinetic experiments showed an average relative rate ratio of 3/1 for
      microwave versus conventional heating and preparative experiments showed an
      average relative conversion ratio of 4.5/1 during the initial 120 min, a period
      approximating one half-life of the isotope. The microwave method described was
      used to prepare previously unreported 2'-(2-fluoro-4-pyridyl)-11beta,17,21
      trihydroxy-16alpha-methyl-20-oxo-pregn-4-eno-[3,2-c]-pyrazole, which was
      evaluated for biological activity.

PMID- 16644223
TI  - Effect of 4-substitution on psychotomimetic activity of 2,5-dimethoxy
      amphetamines as studied by means of different substituent parameter scales.
AB  - Electron-withdrawing substituents at position 4 of 2,5-dimethoxy-substituted
      amphetamines increase, whereas electron-donating substituents decrease the
      psychotomimetic activity. The origin of this clearly localized effect is
      discussed. The uses of modified Hammett substituent scales (sigma(-) and
      sigma(+)), and especially the good sigma(+) correlation, strongly suggest that
      electron-donating substituents decrease the biological activity through a
      specific effect relating to the extent of the conjugative electron release from
      the 5-methoxy group to the phenyl ring.

PMID- 16644224
TI  - A prospective, randomised study comparing two techniques of autologous
      chondrocyte implantation for osteochondral defects in the knee: Periosteum
      covered versus type I/III collagen covered.
AB  - INTRODUCTION: The results for autologous chondrocyte implantation (ACI) in the
      treatment of full thickness chondral defects in the knee are encouraging. At
      present two techniques have been described to retain the chondrocyte suspension
      within the defect. The first involves using a periosteal cover (ACI-P) and the
      second involves using a type I/III collagen membrane (ACI-C). To the authors
      knowledge there are no comparative studies of these two techniques in the current
      literature. We have therefore undertaken such a study to establish if there is a
      difference between the 2 techniques based on a clinical and arthroscopic
      assessment. METHODS: A total of 68 patients with a mean age of 30.52 years with
      symptomatic articular cartilage defects were randomised to have either ACI-P (33
      patients) or ACI-C (35 patients). The mean defect size was 4.54 cm2. All patients
      were followed up at 24 months. RESULTS: A clinical and functional assessment
      showed that 74% of patients had a good or excellent result following the ACI-C
      compared with 67% after the ACI-P at 2 years. Arthroscopy at 1 year also
      demonstrated similar results for both techniques. However, 36.4% of the ACI-P
      grafts required shaving for hypertrophy compared with none for the ACI-C grafts
      at 1 year. DISCUSSION: This study has shown no statistical difference between the
      clinical outcome of ACI-C versus ACI-P at 2 years. A significant number of
      patients who had the ACI-P required shaving of a hypertrophied graft. We conclude
      that there is no advantage in using periosteum as a cover for retaining
      chondrocytes within an osteochondral defect; as a result we advocate the use of
      an alternative cover such as a manufactured type I/III collagen membrane.

PMID- 16644225
TI  - Precision of computer-assisted core decompression drilling of the knee.
AB  - INTRODUCTION: Core decompression by exact drilling into the ischemic areas is the
      treatment of choice in early stages of osteonecrosis of the femoral condyle.
      Computer-aided surgery might enhance the precision of the drilling and lower the
      radiation exposure time of both staff and patients. The aim of this study was to
      evaluate the precision of the fluoroscopically based VectorVision-navigation
      system in an in vitro model. MATERIALS AND METHODS: Thirty sawbones were prepared
      with a defect filled up with a radiopaque gypsum sphere mimicking the
      osteonecrosis. 20 sawbones were drilled by guidance of an intraoperative
      navigation system VectorVision (BrainLAB, Munich, Germany). Ten sawbones were
      drilled by fluoroscopic control only. RESULTS: A statistically significant
      difference with a mean distance of 0.58 mm in the navigated group and 0.98 mm in
      the control group regarding the distance to the desired mid-point of the lesion
      could be stated. Significant difference was further found in the number of
      drilling corrections as well as radiation time needed. CONCLUSION: The
      fluoroscopic-based VectorVision-navigation system shows a high feasibility and
      precision of computer-guided drilling with simultaneously reduction of radiation
      time and therefore could be integrated into clinical routine.

PMID- 16644226
TI  - A novel antimicrobial epoxide isolated from larval Galleria mellonella infected
      by the nematode symbiont, Photorhabdus luminescens (Enterobacteriaceae).
AB  - A novel antimicrobial epoxide, 2-isopropyl-5-(3-phenyl-oxiranyl)-benzene-1,3-diol
      (1), was identified from larval Galleria mellonella infected by a symbiotically
      associated bacterium-nematode complex (Photorhabdus luminescens C9
      Heterorhabditis megidis 90). Its structure was determined with spectroscopic
      analysis and confirmed by chemical synthesis starting from a known antibiotic, 2
      isopropyl-5-(2-phenylethenyl)-benzene-1,3-diol (2). Epoxide 1 was active against
      Bacillus subtilis, Escherichia coli, Streptococcus pyogenes, and a drug
      resistant, clinical strain of Staphylococcus aureus (RN4220) with minimum
      inhibitory concentrations in the range of 6.25-12.5 microg/ml. Epoxide 1 was
      cytotoxic against human cancer cell lines, MCF-7 wt, H460, and Jurkat, with
      GI(50) of 2.14, 0.63, and 0.42 microM, respectively, but was less toxic on
      normal, mouse splenic lymphocytes with a GI(50) of 45.00 microM.

PMID- 16644227
TI  - Synthesis, cannabinoid receptor activity, and enzymatic stability of reversed
      amide derivatives of arachidonoyl ethanolamide.
AB  - Retroanandamide (2f) and its 10 analogues (1a-e, 2a-e) were synthesized and
      evaluated for the cannabinoid receptor activation by a [35S]GTPgammaS binding
      assay using rat cerebellar membranes, and Chinese hamster ovary cell membranes
      expressing human CB2 receptors. The primary goal of the study was to develop
      cannabinoid receptor agonists having improved enzymatic stability compared to
      endogenous N-arachidonoyl ethanolamide (AEA). Furthermore, by reversing the amide
      bond of AEA, the formation of arachidonic acid would be prevented. Finally, an
      effect of the carbonyl carbon position on the cannabinoid receptor activity was
      explored by synthesizing retroanandamide analogues having different chain lengths
      (1a-e, C19; 2a-f, C20). All the synthesized compounds, except 2c, behaved as
      partial agonists for the both cannabinoid receptors. In rat brain homogenate, the
      reversed amides possessed significantly higher stability against FAAH induced
      degradation than AEA. Therefore, the reversed amide analogues of AEA may serve as
      enzymatically stable structural basis for the drug design based on the endogenous
      cannabinoids.

PMID- 16644228
TI  - Ultrastructural study of the ovary of the sugarcane spittlebug Mahanarva
      fimbriolata (Hemiptera).
AB  - The present study describes the ultrastructure of meroistic telotrophic ovaries
      of the sugarcane spittlebug Mahanarva fimbriolata. In this type of ovary, nurse
      cells, oogonia, and prefollicular tissue are located at the terminal (distal)
      regions or tropharium of ovarioles. Oocytes in different developmental stages,
      classified from I to V, are observed in the vitellarium. Stage I oocytes do not
      exhibit intercellular spaces in the follicular epithelium, suggesting that
      synthesis and production of yolk during this stage occurs only through endogenous
      processes. Small yolk granules of different electron densities are present in the
      cytoplasm. Few lipid droplets are observed. Stage II oocytes exhibit small
      intercellular spaces in the follicular epithelium. More protein as well as lipid
      yolk granules are observed in the cytoplasm. In stage III oocytes, intercellular
      spaces in the follicular epithelium are larger than those observed in the
      previous stage. Electrondense protein granules of various sizes, larger than
      those observed in stage II oocytes predominate in the cytoplasm. Smaller lipid
      droplets are also present. In stage IV oocytes, the follicular epithelium
      exhibits large intercellular spaces. Our data clearly indicate that the opening
      of these spaces in the follicular epithelium of M. fimbriolata oocytes increases
      as the intake of exogenous proteins intensifies, that is, in stages IV and V
      oocytes. During these stages, granular yolk becomes viscous due to the lysis of
      granules. In stage V oocytes, viscous yolk predominates in the cytoplasm. This
      type of yolk, however, has not been described for other orders of insects. The
      chorion of M. fimbriolata oocytes consists of an external layer (exochorion) and
      an internal one (endochorion), which is in direct contact with the oocyte.
      Numerous small pores that probably facilitate oxygenation of the internal
      structures inside the eggs are observed in the exochorion.

PMID- 16644229
TI  - Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in
      which recessive mutations cause ataxia and dominant mutations cause motor neuron
      disease.
AB  - A severe recessive cerebellar ataxia, Ataxia-Oculomotor Apraxia 2 (AOA2) and a
      juvenile onset form of dominant amyotrophic lateral sclerosis (ALS4) result from
      mutations of the Senataxin (SETX) gene. To begin characterization this disease
      protein, we developed a specific antibody to the DNA/RNA helicase domain of SETX.
      In murine brain, SETX concentrates in several regions, including cerebellum,
      hippocampus and olfactory bulb with a general neuronal expression profile,
      colocalizing with NeuN. In cultured cells, we found that SETX was cytoplasmically
      diffuse, but in the nucleus, SETX was punctate, colocalizing with fibrillarin, a
      marker of the nucleolus. In differentiated non-cycling cells, nuclear SETX was
      not restricted to the nucleolus but was diffuse within the nucleoplasm,
      suggesting cell-cycle-dependent localization. SETX missense mutations cluster
      within the N-terminus and helicase domains. Flag tagging at the N-terminus caused
      protein mislocation to the nucleoplasm and failure to export to the cytoplasm,
      suggesting that the N-terminus may be essential for correct SETX localization. We
      report here the first characterization of SETX protein, which may provide future
      insights into a new mechanism leading to neuron death.

PMID- 16644230
TI  - Responses of citrus plants to ozone: leaf biochemistry, antioxidant mechanisms
      and lipid peroxidation.
AB  - The effects of ozone upon 3-year-old trees of Clementina mandarin (Citrus
      clementina Hort. ex Tan.) cv. Marisol exposed for 12 months to ambient (10 nl l(
      1)) and high (30 and 65 nl l(-1)) concentrations in open top chambers (OTCs) were
      investigated. The data showed that in leaves, ozone reduced total chlorophylls,
      carotenoid and carbohydrate concentration, and increased 1-aminocyclopropane-1
      carboxylic acid (ACC) content and ethylene production. In treated plants, the
      ascorbate leaf pool was decreased, while lipid peroxidation and solute leakage
      were significantly higher than in ozone-free controls. The data indicated that
      ozone triggered protective mechanisms against oxidative stress in citrus.

PMID- 16644231
TI  - Involvement of phospholipases C and D in early response to SAR and ISR inducers
      in Brassica napus plants.
AB  - Phospholipid signaling is an important component in eukaryotic signal
      transduction pathways. In plants, it plays a key role in growth and development
      as well as in responses to environmental stresses, including pathogen attack. We
      investigated the involvement of both phospholipase C (PLC, EC 3.1.4.11) and D
      (PLD, EC 3.1.4.4) in early responses to the treatment of Brassica napus plants
      with the chemical inducers of systemic acquired resistance (SAR): salicylic acid
      (SA), benzothiadiazole (BTH), and with the inducer mediating the induced systemic
      resistance (ISR) pathway, methyl jasmonate (MeJA). Rapid activation (within 0.5-6
      h treatment) of the in vitro activity level was found for phosphatidyl inositol
      4,5 bisphosphate (PIP2)-specific PLC (PI-PLC) and three enzymatically different
      forms of PLD: conventional PLDalpha, PIP2-dependent PLD beta/gamma, and oleate
      stimulated PLDdelta. The strongest response was found in case of cytosolic PIP2
      dependent PLD beta/gamma after BTH treatment. PLDdelta was identified in B. napus
      leaves and was very rapidly activated after MeJA treatment with the highest
      degree of activation compared to the other PLD isoforms. Interestingly, an
      increase in the amount of protein was observed only for PLDgamma and/or delta
      after ISR induction, but later than the activation occurred. These results show
      that phospholipases are involved in very early processes leading to systemic
      responses in plants and that they are most probably initially first activated on
      post translational level.

PMID- 16644232
TI  - Analysis of mechanical stress in reconstruction plates for bridging mandibular
      angle defects.
AB  - INTRODUCTION: The objective of the present study was to evaluate the mechanical
      stress in reconstruction plates and the screw-plate-bone interface used in
      bridging a mandibular angle defect by means of the finite element method (FEM).
      The influence of plate geometry as well as the configuration and the diameter of
      the screws on the mechanical stress distribution was to be determined at the same
      time and was used as the basis for developing suggestions to optimize the design
      of the reconstruction plates. MATERIAL: Based on the geometrical data of a human
      mandible, an angle defect bridged by a titanium reconstruction plate was
      generated and exposed to chewing force. First a reconstruction plate was tightly
      fixed with M2.7 titanium screws. Then, plate design, screw configuration and
      screw diameter were varied. The mechanical stress was calculated according to von
      Mises stress hypothesis. RESULTS: In the standard reconstruction plate, the
      result of the finite element analysis revealed stress resulting from the
      simulated functional loadings which far exceeded the strengths of the components.
      Possible clinical consequences could be a fatigue fracture of the plate itself,
      gradual loosening of the osteosynthesis screws and loss of bone. The stress can
      be reduced to less than half by increasing the diameter of the screw threads 1.5
      fold. CONCLUSION: Maximizing the interface between bone and reconstruction plate
      had a favourable effect. As a consequence of the large interface and a triangular
      or square configuration of the screws, the stresses could be substantially
      reduced, the plate could be made thinner and thus better adapted to the mandible.
      As a preliminary result, the newly designed reconstruction plate could be thinned
      in areas subject to less mechanical stress.

PMID- 16644233
TI  - Silicone rubber mould cast polyethylmethacrylate-hydroxyapatite plate used for
      repairing a large skull defect.
AB  - INTRODUCTION: Reconstruction of the cranial vault is performed for various
      reasons and precise repair of the defect is important. A modified method of
      cranioplasty is presented using three-dimensional (3D) models and
      polyethylmethacrylate mixed with hydroxyapatite, cast in a silicone rubber mould.
      PATIENT AND METHOD: A large custom made cranial implant was produced using data
      acquired from 3D computer tomography, rapid prototyping and cast in a silicone
      rubber mould. This plate was then applied to a 53 year-old man who had undergone
      a decompressive fronto-parieto-temporo-occipital craniotomy. The bone flap had
      been lost due to infection. The cranioplasty was performed at 1 year after the
      initial operation. RESULTS: The cranial plate fitted precisely into the defect
      and needed no correction at the time of surgery. The stability of the
      reconstruction plate was increased by the presence of thin margins allowed by
      silicone rubber elasticity. No complications occurred and the final functional
      and aesthetic results were good. CONCLUSION: The use of 3D imaging and rapid
      prototyping allow precise repair of large skull defects, with good aesthetic and
      functional results. At the same time, silicone rubber moulds permit the
      production of very thin details needed not only for cosmetic reasons but for
      reconstruction plate stability as well.

PMID- 16644234
TI  - Adipose tissue lipolysis as a metabolic pathway to define pharmacological
      strategies against obesity and the metabolic syndrome.
AB  - Adipose tissue lipolysis is the catabolic process leading to the breakdown of
      triglycerides stored in fat cells and release of fatty acids and glycerol. Recent
      work has revealed that lipolysis is not a simple metabolic pathway stimulated by
      catecholamines and inhibited by insulin. There have been new discoveries on the
      endocrine and paracrine regulation of lipolysis and on the molecular mechanisms
      of triglyceride hydrolysis. Catecholamines modulate lipolysis through lipolytic
      beta-adrenoceptor and antilipolytic alpha2-adrenoceptor. Recent studies have
      allowed a better understanding of the relative contribution of the two types of
      receptors and provided evidence for the in vivo involvement of alpha2
      adrenoceptors in the physiological control of subcutaneous adipose tissue
      lipolysis. A puzzling observation is the characterization of a residual
      catecholamine-induced lipolysis in mice deficient in beta-adrenoceptors. A novel
      lipolytic system has been characterized in human fat cells. Natriuretic peptides
      stimulate lipolysis through a cGMP-dependent pathway. There are other lipolytic
      pathways active in human fat cells which importance is not fully understood.
      Forty years after the description of the antilipolytic effect of nicotinic acid,
      the receptors have been identified. Adrenomedullin which is produced by
      adipocytes exert an antilipolytic effect through an indirect mechanism involving
      nitric oxide. The molecular details of the lipolytic reaction are not fully
      understood. The role of the lipases has been re-evaluated with the cloning of
      adipose triglyceride lipase. Hormone-sensitive lipase appears as the major lipase
      for catecholamine and natriuretic peptide-stimulated lipolysis whereas adipose
      triglyceride lipase mediates the hydrolysis of triglycerides during basal
      lipolysis. Translocation of hormone-sensitive lipase bound to the adipocyte lipid
      binding protein to the lipid droplet seems to be an important step during
      lipolytic activation. Re-organization of the lipid droplet coating by perilipins
      facilitates the access of the enzyme. The role of other lipid-interacting
      proteins in lipolysis is still unclear. The proteins involved in the lipolytic
      process constitute drug targets for the treatment of obesity and the metabolic
      syndrome. The oldest example is nicotinic acid (niacin) used as a hypolipidaemic
      drug. A first approach consists in molecules stimulating lipolysis and oxidation
      of the released fatty acids to decrease fat stores. A second approach is a
      chronic inhibition of lipolysis to diminish plasma fatty acid level which is a
      central feature of the metabolic syndrome.

PMID- 16644235
TI  - Anti-ischaemic effect of ivabradine.
AB  - Ivabradine, the first representative of a new class of exclusive heart rate
      reducing agents, selectively inhibits the I(f) current in the sinoatrial node.
      The direct electrophysiological consequence of this inhibition is a reduction in
      the slope of the diastolic depolarisation curve and a decrease in heart rate.
      Pharmacological inhibition of the I(f) current with ivabradine has been shown to
      preserve coronary vasodilatation upon exercise, i.e., myocardial perfusion, with
      no negative inotropic effects and maintenance of cardiac contractility.
      Ivabradine protects the myocardium during ischaemia, improves left ventricular
      function in congestive heart failure, and reduces remodelling subsequent to
      myocardial infarction. Pure heart rate reduction by specific and selective I(f)
      inhibition decreases oxygen demand, improves myocardial energetics and improves
      perfusion of the ischaemic myocardium. We can expect distinct clinical benefits
      from long-term heart rate reduction in patients with chronic ischaemic disease.

PMID- 16644236
TI  - Effects of estrogen variation on neural correlates of emotional response
      inhibition.
AB  - Despite behavioral evidence that variation in ovarian hormones is associated with
      changes in affect, the neural basis of these processes is poorly understood. We
      combined functional magnetic resonance imaging (fMRI) with quantitative analysis
      of ovarian hormones in a within-subject design to investigate brain activation
      patterns during affective response inhibition, comparing activation between the
      early follicular (low estrogen and progesterone) and mid-luteal (high estrogen
      and progesterone) phases of the menstrual cycle in healthy women. There was
      significantly increased activation in the anterior cingulate and dorsolateral
      prefrontal cortex (DLPFC) while inhibiting response to positive words during the
      luteal, compared to the follicular phase. Furthermore, luteal phase estradiol
      level positively correlated with DLPFC activation while inhibiting response to
      positive words and negatively correlated with activation in several structures
      while inhibiting response to negative words, supporting estrogen's modulation of
      affective processing.

PMID- 16644237
TI  - Three dimensional optical imaging of blood volume and oxygenation in the neonatal
      brain.
AB  - Optical methods provide a means of monitoring cerebral oxygenation in newborn
      infants at risk of brain injury. A 32-channel optical imaging system has been
      developed with the aim of reconstructing three-dimensional images of regional
      blood volume and oxygenation. Full image data sets were acquired from 14 out of
      24 infants studied; successful images have been reconstructed in 8 of these
      infants. Regional variations in cerebral blood volume and tissue oxygen
      saturation are present in healthy preterm infants. In an infant with a large
      unilateral intraventricular haemorrhage, a corresponding region of low oxygen
      saturation was detected. These results suggest that optical tomography may
      provide an appropriate technique for investigating regional cerebral
      haemodynamics and oxygenation at the cotside.

PMID- 16644238
TI  - Multi-resolution Bayesian regression in PET dynamic studies using wavelets.
AB  - In the kinetic analysis of dynamic PET data, one usually posits that the
      variation of the data through one dimension, time, can be described by a
      mathematical model encapsulating the relevant physiological features of the
      radioactive tracer. In this work, we posit that the remaining dimension, space,
      can also be modeled as a physiological feature, and we introduce this concept
      into a new computational procedure for the production of parametric maps. An
      organ and, in the instance considered here, the brain presents similarities in
      the physiological properties of its elements across scales: computationally, this
      similarity can be implemented in two stages. Firstly, a multi-scale decomposition
      of the dynamic frames is created through the wavelet transform. Secondly, kinetic
      analysis is performed in wavelet space and the kinetic parameters estimated at
      low resolution are used as priors to inform estimates at higher resolutions.
      Kinetic analysis in the above scheme is achieved by extension of the Patlak
      analysis through Bayesian linear regression that retains the simplicity and speed
      of the original procedure. Application to artificial and real data (FDG and
      FDOPA) demonstrates the ability of the procedure to reduce remarkably the
      variance of parametric maps (up to 4-fold reduction) without introducing sizeable
      bias. Significance of the methodology and extension of the procedure to other
      data (fMRI) and models are discussed.

PMID- 16644239
TI  - The neural correlates of cross-modal interaction in speech perception during a
      semantic decision task on sentences: a PET study.
AB  - Speech perception in face-to-face conversation involves processing of speech
      sounds (auditory) and speech-associated mouth/lip movements (visual) from a
      speaker. Using PET where no scanner noise was present, brain regions involved in
      speech cue processing were investigated with the normal hearing subjects with no
      previous lip-reading training (N = 17) carrying out a semantic plausibility
      decision on spoken sentences delivered in a movie file. Multimodality was ensured
      at the sensory level in all four conditions. Sensory-specific speech cue of one
      sensory modality, i.e., auditory speech (A condition) or mouth movement (V
      condition), was delivered with a control stimulus of the other modality whereas
      speech cues of both sensory modalities (AV condition) were delivered during
      bimodal condition. In comparison to the control condition, extensive activations
      in the superior temporal regions were observed bilaterally during the A condition
      but these activations were reduced in extent and left lateralized during the AV
      condition. Polymodal region such as left posterior superior temporal sulcus
      (pSTS) involved in cross-modal interaction/integration of audiovisual speech was
      found to be activated during the A and more so during the AV conditions but not
      during the V condition. Activations were observed in Broca's (BA 44), medial
      frontal (BA 8), and anterior ventrolateral prefrontal (BA 47) regions in the left
      during the V condition, where lip-reading performance was less successful.
      Results indicated that the speech-associated lip movements (visual speech cue)
      rendered suppression on the activity in the right auditory temporal regions.
      Overadditivity (AV > A + V) observed in the right postcentral region during the
      bimodal condition relative to the sum of unimodal speech conditions was also
      associated with reduced activity during the V condition. These findings suggested
      that visual speech cue could exert an inhibitory modulatory effect on the brain
      activities in the right hemisphere during the cross-modal interaction of
      audiovisual speech perception.

PMID- 16644240
TI  - Processing the acoustic effect of size in speech sounds.
AB  - The length of a vocal tract is reflected in the sound it is producing. The length
      of the vocal tract is correlated with body size and humans are very good at
      making size judgments based on the acoustic effect of vocal tract length only.
      Here we investigate the underlying mechanism for processing this main auditory
      cue to size information in the human brain. Sensory encoding of the acoustic
      effect of vocal tract length (VTL) depends on a time-stabilized spectral scaling
      mechanism that is independent of glottal pulse rate (GPR, or voice pitch); we
      provide evidence that a potential neural correlate for such a mechanism exists in
      the medial geniculate body (MGB). The perception of the acoustic effect of
      speaker size is influenced by GPR suggesting an interaction between VTL and GPR
      processing; such an interaction occurs only at the level of non-primary auditory
      cortex in planum temporale and anterior superior temporal gyrus. Our findings
      support a two-stage model for the processing of size information in speech based
      on an initial stage of sensory analysis as early as MGB, and a neural correlate
      of the perception of source size in non-primary auditory cortex.

PMID- 16644241
TI  - Language experience shapes fusiform activation when processing a logographic
      artificial language: an fMRI training study.
AB  - The significant role of the left midfusiform cortex in reading found in recent
      neuroimaging studies has led to the visual word form area (VWFA) hypothesis. This
      hypothesis suggests that years of experience reading native language change the
      visual expertise of this region to be especially sensitive to the visual form of
      native language. The present study aimed at testing this hypothesis by exploring
      the role of language experience in shaping the fusiform activation. We designed a
      logographic artificial language (LAL) using the visual form and pronunciation of
      Korean Hangul characters (but their correspondence was shuffled) and assigning
      arbitrary meanings to these characters. Twelve native Chinese Mandarin speakers
      (6 male and 6 female, 18 to 21 years old) with no prior knowledge of Korean
      language were trained in the visual form of these characters for 2 weeks,
      followed by 2 weeks each of phonological and semantic training. Behavioral data
      indicated that training was effective in increasing the efficiency of visual form
      processing and establishing the connections among visual form, sounds, and
      meanings. Imaging data indicated that at the pre-training stage, subjects showed
      stronger activation in the fusiform regions for LAL than for Chinese across both
      one-back visual matching task and the passive viewing task. Visual form training
      significantly decreased the activation of bilateral fusiform cortex and the left
      inferior occipital cortex, whereas phonological training increased activation in
      these regions, and the right fusiform remained more active after semantic
      training. Increased activations after phonological and semantic training were
      also evident in other regions involved in language processing. These findings
      thus do not seem to be consistent with the visual-expertise-induced-sensitivity
      hypothesis about fusiform regions. Instead, our results suggest that visual
      familiarity, phonological processing, and semantic processing all make
      significant but different contributions to shaping the fusiform activation.

PMID- 16644242
TI  - Molecular phylogeny and a chronology of diversification for "phractocephaline"
      catfishes (Siluriformes: Pimelodidae) based on mitochondrial DNA and nuclear
      recombination activating gene 2 sequences.
AB  - The Maracaibo basin in northwestern Venezuela is home to over 108 species of
      freshwater fishes, over half of which occur nowhere else. The rise of the Merida
      Andes between 8 and 10 million years ago is believed to have divided a
      preexisting biota and facilitated allopatric speciation. The distinctive
      "phractocephaline" clade of pimelodid catfishes has a distribution that includes
      the Maracaibo historically and today is represented by Perrunichthys (Maracaibo
      endemic), Leiarius, Phractocephalus, and Steindachneridion. A resolved and well
      supported phylogeny was obtained from the phylogenetic analysis of over 3.4kb
      (including cytochrome b, NADH dehydrogenase subunit 1, recombination activating
      gene subunit 2). Rates of divergence among "phractocephalines" were calibrated
      with fossil material and the Merida uplift. These independent calibrators
      provided different node-age estimates when the rates were applied separately to
      the gene partitions (mtDNA and rag2). Node-age discrepancies were particularly
      evident at older nodes. This is due to two factors: (1) multiple substitution of
      mtDNA underestimates the amount of change and therefore time since cladogenesis,
      whereas (2) calibration of an ancient node with fossils produces an artificially
      slow rate (due to the masking of divergence through multiple substitution) that
      overestimates time when applied to younger nodes. Node-age estimates provided by
      the more slowly evolving rag2 sequences were more consistent with other sources
      of historical inference, e.g., paleogeography and the fossil record. Given these
      points, we provide a synthetic chronology of diversification and discuss the
      reasons for its preference. The phylogeny and synthetic chronology suggest
      Perrunichthys perruno (Maracaibo endemic) and Leiarius pictus (Orinoco and
      Guianas) to be a vicariant species pair that last shared a common ancestor during
      the period of Merida uplift.

PMID- 16644243
TI  - Molecular phylogeny of silkmoths reveals the origin of domesticated silkmoth,
      Bombyx mori from Chinese Bombyx mandarina and paternal inheritance of Antheraea
      proylei mitochondrial DNA.
AB  - Molecular phylogeny of some of the economically important silkmoths was derived
      using three mitochondrial genes, 12S rRNA, 16S rRNA, and COI, and the control
      region (CR). Maximum likelihood (ML) analyses showed two distinct clades, one
      consisting of moths from Bombycidae family and the other from Saturniidae family.
      The mitochondrial CR showed length polymorphisms with indels. The ML analyses for
      complete mitochondrial genome sequences of Bombyx mori (strains Aojuku, C108,
      Backokjam, and Xiafang), Japanese and Chinese strains of B. mandarina (Japanese
      mandarina and Chinese mandarina) and, Antheraea pernyi revealed two distinct
      clades, one comprising of B. mori strains and the other with B. mandarina, and A.
      pernyi forming an outgroup. Pairwise distances revealed that all of the strains
      of B. mori studied are closer to Chinese than to Japanese mandarina. Phylogenetic
      analyses based on whole mitochondrial genome sequences, the finding of a tandem
      triplication of a 126bp repeat element only in Japanese mandarina, and chromosome
      number variation in B. mandarina suggest that B. mori must have shared its recent
      common ancestor with Chinese mandarina. Another wild species of the Bombycidae
      family, Theophila religiosa, whose phylogenetic status was not clear, clustered
      together with the other bombycid moths in the study. Analysis of the
      interspecific hybrid, A. proylei gave evidence for paternal inheritance of
      mitochondrial DNA.

PMID- 16644244
TI  - Genetic diversity within the Albugo candida complex (Peronosporales, Oomycota)
      inferred from phylogenetic analysis of ITS rDNA and COX2 mtDNA sequences.
AB  - Albugo candida is a destructive fungus infecting brassicaceous hosts. The genetic
      diversity within the A. candida complex from various host plants was investigated
      by sequence analysis of the internal transcribed spacer (ITS) region of rDNA and
      the cytochrome c oxidase subunit II (COX2) region of mtDNA. The aligned
      nucleotide sequences of A. candida shared significantly high distances, up to
      20.4 and 8.9%, in two genes. The phylogenetic trees, obtained using the Bayesian
      method and maximum parsimony analysis, showed two separate groups that
      corresponded to the host genera. Group I included A. candida isolates infecting
      Arabis, Autrieta, Berteroa, Biscutella, Brassica, Cardaminopsis, Diplotaxis,
      Eruca, Erysimum, Heliophila, Iberis, Lunaria, Raphanus, Sinapis, Sisymbrium, and
      Thlaspi. Group II contained all isolates from Capsella, Descurainia,
      Diptychocarpus, Draba, and Lepidium. The genetic similarities between the two
      genes among isolates within Group I were 99.0-100% and 99.6-100%, while those
      within Group II were 90.4-100% and 91.1-100%, respectively, showing considerably
      lower values than for Group I. The A. candida isolates from Capsella bursa
      pastoris in Korea are clearly separated by sequence analysis for the two genes
      compared to those from Wales, England, and the USA. Based on the molecular data
      from the two genes, we suggest the high degree of genetic diversity exhibited
      within A. candida complexes warrants their division into several distinct
      species.

PMID- 16644245
TI  - Reliability of an efficient MRI-based method for estimation of knee cartilage
      volume using surface registration.
AB  - OBJECTIVE: To aid in detection of osteoarthritis (OA) progression in serial
      magnetic resonance (MR) scans, we assessed feasibility and accuracy of rapid 3D
      image registration of the tibial plateau in normal and arthritic subjects, and
      inter-scan reliability of semi-automated cartilage volume measurement from these
      images. DESIGN: Two T1 fat-suppressed knee MR scans were obtained 2 weeks apart
      in healthy adults (n = 9, age 23-48 years). Four scans of each of three patients
      with established OA were obtained over 2 years. At baseline, the tibial surface
      was digitized by semi-automated edge detection and medial tibial plateau
      cartilage volume was calculated from high-intensity voxels within a manually
      drawn region of interest (ROI). In subsequent scans, the digitized tibial surface
      was registered to the baseline location by photogrammetric 3D coordinate
      transformation, and cartilage volume was automatically recalculated by reuse of
      the ROI. We measured registration accuracy by root mean square (RMS) distance
      between registered tibial surfaces. RESULTS: In normals, RMS distance between
      tibial surfaces in baseline and subsequent scans was 1/3 voxel length (0.121 mm),
      and medial tibial plateau cartilage volumes varied by 1.4+/-3.2%. Despite change
      in cartilage volumes by up to 20% over 2 years in arthritic patients, surface
      registration accuracy was unaffected (0.122 mm). User-supervised processing time
      was 15 min at baseline and 7 min in subsequent scans. CONCLUSION: Tibial surfaces
      on magnetic resonance imaging (MRI) can be rapidly and accurately co-registered,
      even in arthritic knees, allowing direct visualization of changes over time.
      Compared to most current methods, cartilage volume measurement in registered
      images is faster and has equivalent inter-scan reliability in initially normal
      subjects.

PMID- 16644246
TI  - Expression of the PTH/PTHrP receptor in chondrogenic cells during the repair of
      full-thickness defects of articular cartilage.
AB  - OBJECTIVE: We studied the accumulation of parathyroid hormone (PTH)/PTHrP
      receptor-positive mesenchymal cells using double immunohistochemistry and
      examined whether this correlated with the subsequent regeneration of 3-mm
      diameter full-thickness defects of articular cartilage. MATERIALS AND METHODS:
      Cylindrical full-thickness articular cartilage defects (3 mm) were artificially
      created in the femoral trochlea of male adolescent Japanese white rabbits (n =
      210) with a hand-drill. Recombinant human PTH(1-84) was then administered into
      the defect cavities with an osmotic pump for either 2 or 4 weeks post-injury.
      Following PTH treatment, the repair processes in the cartilage defects were
      histologically examined. Double immunostaining analyses for the PTH/PTH-related
      peptide (PTHrP) receptor and proliferating cell nuclear antigen (PCNA) in the
      regenerating tissues were then performed. RESULTS: Activation of PTH/PTHrP
      receptor signaling by hPTH(1-84) results in the inhibition of chondrogenic
      differentiation in full-thickness articular cartilage defects. At the conclusion
      of the 2-week PTH treatment, the defect cavities were filled with
      undifferentiated mesenchymal cells, which were similar to the controls. In
      addition, almost all of these cells localized at the center of the injuries were
      both PTH/PTHrP receptor- and PCNA-positive. In contrast, after prolonged PTH
      treatment for 4 weeks, there was no indication of a cartilaginous repair response
      and cells that had migrated to the defect cavities were found to have
      irreversibly lost expression of the PTH/PTHrP receptor. CONCLUSIONS: The
      chondrogenic capacity of cells that had migrated to the area of these defect
      cavities is closely associated with their ability to express the PTH/PTHrP
      receptor. Moreover, these cells maintain their chondrogenic potential within only
      a limited time-span of 2 weeks.

PMID- 16644247
TI  - Esterase-activated chromane-sydnonimine prodrug hybrids.
AB  - The preparation and characterization of two vitamin E analogs-sydnonimine
      conjugates, delta-tocopheryloxycarbonyl-3-morpholinosydnonimine (2) and
      troloxoxycarbonyl-3-morpholinosydnonimine (3), in which the hydroxyl group of the
      tocopheryl moieties is linked via an enzymatically cleavable urethane group to
      the sydnone moiety is described. In the presence of porcine liver esterase, these
      tocopheryl-sydnonimine conjugates generated the expected antioxidant moieties,
      i.e., delta-tocopherol or Trolox, and were found to convert oxyhemoglobin to
      methemoglobin at 37 degrees C in 50 mM phosphate buffer at pH 7.4, thus providing
      evidence for nitric oxide release. Their potency as antioxidants was indirectly
      studied by associating the two products of the hydrolysis, SIN-1, and delta
      tocopherol or Trolox. Our findings suggest that unlike the other members of the
      sydnonimine family these chromane-sydnonimine derivatives do not act as
      peroxynitrite donors, and require enzymatic bioactivation before nitric oxide or
      nitroxyl anion (NO(-)) can be released.

PMID- 16644248
TI  - Effects of poly(ADP-ribose) polymerase inhibition on dysfunction of non
      adrenergic non-cholinergic neurotransmission in gastric fundus in diabetic rats.
AB  - Diabetes mellitus compromises nitric oxide (NO)-mediated endothelium-dependent
      relaxation of blood vessels, which has been linked to the excessive generation of
      reactive oxygen species. There are also deleterious effect on nitrergic
      innervation, contributing to autonomic neuropathy symptoms such as impotence and
      gastroporesis. Poly(ADP-ribose) polymerase (PARP) is a nuclear protein stimulated
      by DNA damage, caused, for example, by oxidative stress. Activation has been
      linked to impaired endothelial nitric oxide synthase (eNOS)-mediated vasodilation
      in experimental diabetes. There is no information on the potential role of PARP
      in nitrergic nerve dysfunction, therefore, the aim was to examine the effects of
      PARP inhibition, using 3-aminobenzamide (3-AB) on neurally mediated gastric
      fundus relaxation in streptozotocin-induced diabetic rats. Eight weeks of
      diabetes caused a 42.5% deficit in maximum relaxation of in vitro gastric fundus
      strips to electrical stimulation of the non-adrenergic non-cholinergic
      innervation. This was largely prevented or corrected (4 weeks of treatment
      following 4 weeks of untreated diabetes) by 3-AB. Diabetes also markedly
      attenuated the maintenance of relaxation responses to prolonged stimulation, and
      this was partially corrected by 3-AB treatment. Experiments in the presence of
      the NOS inhibitor, N(G)-nitro-L-arginine, and/or blockade of the co-transmitter,
      vasoactive intestinal polypeptide, by alpha-chymotrypsin, showed that the
      beneficial effects of 3-AB were primarily due to improved nitrergic
      neurotransmission. Thus, PARP plays an important role in defective nitrergic
      neurotransmission in experimental diabetes, which may have therapeutic
      implications for treatment of aspects of diabetic autonomic neuropathy.

PMID- 16644249
TI  - Exploring the limits of polarization transfer efficiency in homonuclear three
      spin systems.
AB  - The limits of polarization transfer efficiency are explored for systems
      consisting of three isotropically coupled spins 1/2 in the absence of relaxation.
      An idealized free evolution and control Hamiltonian is studied, which provides an
      upper limit of transfer efficiency (in terms of transfer amplitude and transfer
      time) for realistic homonuclear spin systems with arbitrary Heisenberg-type
      coupling constants J12, J13, and J23. It is shown that optimal control based
      pulse sequences have significantly improved transfer efficiencies compared to
      conventional transfer schemes. An experimental demonstration of optimal
      polarization transfer is given for the case of the carbon spin system of fully
      13C labelled alanine at 62.5 MHz Larmor frequency.

PMID- 16644250
TI  - A 'just-in-time' HN(CA)CO experiment for the backbone assignment of large
      proteins with high sensitivity.
AB  - Among the suite of commonly used backbone experiments, HNCACO presents an
      unresolved sensitivity limitation due to fast 13CO transverse relaxation and
      passive 13Calpha-13Cbeta coupling. Here, we present a high-sensitivity 'just-in
      time' (JIT) HN(CA)CO pulse sequence that uniformly refocuses 13Calpha-13Cbeta
      coupling while collecting 13CO shifts in real time. Sensitivity comparisons of
      the 3-D JIT HN(CA)CO, a CT-HMQC-based control, and a HSQC-based control with
      selective 13Calpha inversion pulses were performed using a 2H/13C/15N labeled
      sample of the 29 kDa HCA II protein at 15 degrees C. The JIT experiment shows a
      42% signal enhancement over the CT-HMQC-based experiment. Compared to the HSQC
      based experiment, the JIT experiment is 16% less sensitive for residues
      experiencing proper 13Calpha refocusing and13Calpha-13Cbeta decoupling. However,
      for the remaining residues, the JIT spectrum shows a 106% average sensitivity
      gain over the HSQC-based experiment. The high-sensitivity JIT HNCACO experiment
      should be particularly beneficial for studies of large proteins to provide 13CO
      resonance information regardless of residue type.

PMID- 16644251
TI  - Spin-diffusion approach for relaxation in bi-spaced periodic one-dimensional
      systems.
AB  - A theoretical model for 1H-1H dipolar nuclear spin relaxation for a bi-spaced
      periodic one-dimensional array of spin 1/2 nuclei has been developed. A diffusion
      equation is formed for such a system by assuming nearest-neighbor interaction and
      isotropic random molecular reorientations. Under spin-diffusion conditions
      (omegatauc>>1), this equation has been solved using Laplace transform for an
      infinite chain. The results are presented for the boundary conditions described
      for truncated driven Nuclear Overhauser effect experiments. The solution is
      further generalized by making the inter-spin spacing as a random variable with a
      Gaussian distribution.

PMID- 16644252
TI  - Fast magnetic resonance imaging and velocimetry for liquids under high flow
      rates.
AB  - We here demonstrate the use of NMR velocity imaging techniques to measure flow in
      a free falling jet of water at speeds up to and on the order of 1m/s. In
      particular, we show how to adapt the RARE imaging method, based on a CPMG
      multiple rf pulse train, so that the real and imaginary parts of the signal may
      be suitably acquired, enabling pulsed gradient spin echo encoding for flow. We
      term this method "soft-pulse-quadrature-cycled PGSE-RARE" or SPQC-PGSE-RARE. We
      further demonstrate the use of a one-dimensional (slice selective) imaging method
      which takes advantage of the cylindrical symmetry of the flow, and considerably
      shortens the image acquisition time.

PMID- 16644253
TI  - Fast empirical pKa prediction by Ewald summation.
AB  - pK(a) calculations for macromolecules are normally performed by solving the
      Poisson-Boltzmann equation, accounting for the different dielectric constants of
      solvent and solute, as well as the ionic strength. Despite the large number of
      successful applications, there are some situations where the current algorithms
      are not suitable: (1) large scale, high-throughput analysis which requires
      calculations to be completed within a fraction of a second, e.g. when permanently
      monitoring pK(a) shifts during a molecular dynamics simulation; (2) prediction of
      pK(a)s in periodic boundaries, e.g. when reconstructing entire protein crystal
      unit cells from PDB files, including the correct protonation patterns at
      experimental pH. Such in silico crystals are needed by 'self-parameterizing'
      molecular dynamics force fields like YASARA YAMBER, that optimize their
      parameters while energy-minimizing high-resolution protein crystals. To address
      both problems, we define an empirical equation that expresses the pK(a) as a
      function of electrostatic potential, hydrogen bonds and accessible surface area.
      The electrostatic potential is evaluated by Ewald summation, which captures
      periodic crystal environments and the uncertainty in atom positions using
      Gaussian charge densities. The empirical proportionality constants are derived
      from 217 experimentally determined pK(a)s, and despite its simplicity, this pK(a)
      calculation method reaches a high overall jack-knifed accuracy, and is fast
      enough to be used during a molecular dynamics simulation. A reliable null-model
      to judge pK(a) prediction accuracies is also presented.

PMID- 16644254
TI  - Cloning and expression of insulin-like growth factors I and II in the shi drum
      (Umbrina cirrosa).
AB  - Insulin-like growth factors (IGFs) are evolutionarily ancient polypeptides, with
      potent metabolic actions, affecting cell development and growth. The IGF system
      consists of two ligands: IGF-I and IGF-II, several binding proteins and high
      affinity transmembrane receptors. To understand growth regulation in the teleost
      shi drum, Umbrina cirrosa, we cloned IGF-I and IGF-II cDNAs, studied their
      expression and determined the cellular localization of IGF-II peptide by
      immunohistochemistry. A fragment of 1110 nucleotides, coding for U. cirrosa IGF-I
      (ucIGF-I), was cloned from liver by PCR. It includes an open reading frame of 561
      nucleotides, encoding a 187 amino acid preproIGF-I. A fragment of 938 nucleotides
      that includes part of the coding sequence and the 3' UTR of IGF-II (ucIGF-II) was
      cloned as well. Sequence analysis of ucIGF-I and ucIGF-II showed a high degree of
      homology with known fish IGF-I and IGF-II. Real-Time PCR showed a higher
      expression of IGF-I and IGF-II in liver, compared to all other tissues analysed.
      IGF-II peptide was detected in larval liver, intestine, gills and heart
      musculature. After metamorphosis, reactivity was particularly evident in the
      kidney and in red fibres of skeletal muscle. These results add novel information
      on the nucleotide sequence of IGF-I and IGF-II in a marine teleost, the shi drum,
      that was recently introduced to the mariculture industry in southern Europe and
      emphasizes the conservation in the 5' UTR of IGF-I among teleosts. Furthermore,
      this study suggests, on the basis of a combined approach of RT-PCR, Real-Time PCR
      and immunohistochemistry that IGF-I and IGF-II are involved in the regulation of
      somatic growth in the shi drum.

PMID- 16644255
TI  - Astaxanthin binding protein in Atlantic salmon.
AB  - The rubicund pigmentation in salmon and trout flesh is unique and is due to the
      deposition of dietary carotenoids, astaxanthin and canthaxanthin in the muscle.
      The present study was undertaken to determine which protein was responsible for
      pigment binding. Salmon muscle proteins were solubilized by sequential
      extractions with non-denaturing, low ionic strength aqueous solutions and
      segregated as such into six different fractions. Approximately 91% of the salmon
      myofibrillar proteins were solubilized under non-denaturing conditions using a
      protocol modified from a method described by Krishnamurthy et al. [Krishnamurthy,
      G., Chang, H.S., Hultin, H.O., Feng, Y., Srinivasan, S., Kelleher. S.D., 1996.
      Solubility of chicken breast muscle proteins in solutions of low ionic strength.
      J. Agric. Food Chem. 44: 408-415.] for the dissolution of avian muscle. To our
      knowledge, this is the first time this solubilization approach has been applied
      to the study of molecular interactions in myofibrillar proteins. Astaxanthin
      binding in each fraction was determined using an in vitro binding assay. In
      addition, SDS-PAGE and quantitative densitometry were used to separate and
      determine the relative amounts of each of the proteins in the six fractions. The
      results showed that alpha-actinin was the only myofibrillar protein correlating
      significantly (P<0.05) with astaxanthin binding. Alpha-actinin was positively
      identified using electrophoretic techniques and confirmed by tandem mass
      spectroscopy. Purified salmon alpha-actinin bound synthetic astaxanthin in a
      molar ratio of 1.11:1.00. The study was repeated using halibut alpha-actinin,
      which was found to have a molar binding ratio of astaxanthin to alpha-actinin of
      0.893:1. These results suggest that the difference in pigmentation between white
      fish and Atlantic salmon is not due to binding capacity in the muscle, but rather
      differences in the metabolism or transport of pigment.

PMID- 16644256
TI  - Exercising in the cold inhibits growth hormone secretion by reducing the rise in
      core body temperature.
AB  - OBJECTIVE: Ambient temperature alters exercise induced GH secretion. It is
      unknown whether temperature affects GH secretion at exercise intensities above
      the anaerobic threshold when other factors may override the relationship seen at
      lower intensities. METHODS:  DESIGN: Cross-over study of ambient temperature on
      exercise induced GH in swimmers and rowers. SETTING: St Thomas Hospital, London.
      SUBJECTS: Ten healthy men (age 21.7+/-0.8 yrs). Five swimmers and five rowers.
      INTERVENTION: Forty-minute exercise test at 105% of anaerobic threshold at room
      temperature (RT) and at 4 degrees C. MEASUREMENTS: Cutaneous and core body
      temperature. Serum GH concentration. RESULTS: Cutaneous body temperature
      increased during exercise at RT but decreased in the cold. Although core
      temperature rose in both settings, the rise was greater at RT (p=0.021). GH
      increased at both temperatures but the onset was delayed by the cold. Peak GH
      tended to be higher at RT (17.4+/-3.6 microg/L vs. 9.5+/-1.5 microg/L, p=0.07).
      Total GH secretion was greater at RT (353.3+/-99.1 microg min/L) than 4 degrees C
      (128.3+/-21.0 microg min/L), p=0.038. Change in core temperature correlated with
      log peak GH (r=0.66, p=0.039) and log incremental GH (r=0.67, p=0.032) when
      exercising at 4 degrees C. There was no difference between swimmers and rowers.
      CONCLUSIONS: Exercise at 4 degrees C reduces GH secretion during exercise at
      intensities above the anaerobic threshold. A change in core body temperature may
      be one mechanism by which exercise induces GH secretion. The difference in GH
      between swimmers and rowers during their respective events relates to the
      conditions under which they compete.

PMID- 16644257
TI  - SMIT1 haploinsufficiency causes brain inositol deficiency without affecting
      lithium-sensitive behavior.
AB  - Two leading hypotheses to explain lithium action in bipolar disorder propose
      either inositol depletion or inhibition of GSK-3 as mechanisms of action.
      Behavioral effects of lithium are mimicked in Gsk-3beta+/- mice, but the
      contribution of inositol depletion to these behaviors has not been tested.
      According to the inositol depletion hypothesis, lithium-sensitive behavior is
      secondary to impaired phosphatidylinositol synthesis caused by inositol
      deficiency. By disrupting the sodium myo-inositol transporter1 gene, SMIT1, we
      show that depletion of brain myo-inositol in SMIT1+/- mice has no effect on
      lithium-sensitive behavior. These findings, taken together with our previous work
      showing that SMIT-/- mice have an even greater depletion of inositol in brain
      with no reduction in phosphatidylinositol levels, are difficult to reconcile with
      the current formulation of the inositol depletion hypothesis.

PMID- 16644258
TI  - Retrospective determination of ceruloplasmin in newborn screening blood spots of
      patients with Wilson disease.
AB  - Wilson disease is an autosomal recessive disorder of copper transport, caused by
      the reduced or absent function of the Wilson disease gene ATP7B on chromosome 13.
      The disease is characterized by reduced incorporation of copper into the
      ceruloplasmin protein and reduced excretion of copper into the bile. Wilson
      disease is effectively treated if detected early. Our study goals were to
      determine the feasibility of a population screening for Wilson disease using
      dried blood spots and to characterize the base-line ceruloplasmin concentration
      in newborn blood spots of patients with Wilson disease. Ceruloplasmin was
      analyzed in dried blood spots obtained from 353 Mayo Clinic pediatric volunteers
      aged from 3 months to 18 years and from 1045 anonymous newborn screening
      specimens using a sandwich enzyme-linked immunosorbent assay. The original
      newborn screening blood spots were retrieved from two patients with Wilson
      disease along with age-matched controls for ceruloplasmin determination. The mean
      (+/-SD) concentration of ceruloplasmin in the pediatric blood spots was 40.0+/
      14.4 mg/dL (range 13.1 to >60 mg/dL) and newborn blood spots was 47.2+/-15.5mg/dL
      (range 6.5 to >60 mg/dL). Ceruloplasmin in the newborn blood spots from two
      Wilson disease patients were 2.6 and 2.8 mg/dL, respectively. The newborns
      affected with Wilson disease had significantly lower ceruloplasmin levels in
      blood spots than unaffected newborns. These findings support that presymptomatic
      screening for Wilson disease using dried blood spots could be possible, even in
      the newborn period.

PMID- 16644259
TI  - [Recommendations for clinical practice. Prevention in maternofetal Rh
      immunization (December 2005)].

PMID- 16644260
TI  - [Openness on results of assisted reproductive techniques: yes].

PMID- 16644261
TI  - Sonolysis of chlorinated compounds in aqueous solution.
AB  - To examine the reaction rates of sonochemical degradation of aqueous phase carbon
      tetrachloride, trichloroethylene and 1,2,3-trichloropropane at various
      temperatures, power intensities, and saturating gases, the batch tests were
      carried out. The degradations of chlorinated hydrocarbons were analyzed as pseudo
      first order reactions and their reaction rate constants were in the range of 10(
      1)-10(-3)/min. The reaction was fast at the low temperature with higher power
      intensity. Also, the reaction went fast with the saturating gas with high
      specific heat ratio, high solubility and low thermal conductivity. The main
      mechanism of destruction of chemicals was believed the thermal combustion in the
      bubble.

PMID- 16644262
TI  - Plaque development, vessel curvature, and wall shear stress in coronary arteries
      assessed by X-ray angiography and intravascular ultrasound.
AB  - The relationships among vascular geometry, hemodynamics, and plaque development
      in the coronary arteries are complex and not yet well understood. This paper
      reports a methodology for the quantitative analysis of in vivo coronary
      morphology and hemodynamics, with particular emphasis placed on the critical
      issues of image segmentation and the automated classification of disease
      severity. We were motivated by the observation that plaque more often developed
      at the inner curvature of a vessel, presumably due to the relatively lower wall
      shear stress at these locations. The presented studies are based on our validated
      methodology for the three-dimensional fusion of intravascular ultrasound (IVUS)
      and X-ray angiography, introducing a novel approach for IVUS segmentation that
      incorporates a robust, knowledge-based cost function and a fully optimal, three
      dimensional segmentation algorithm. Our first study shows that circumferential
      plaque distribution depends on local vessel curvature in the majority of vessels.
      The second study analyzes the correlation between plaque distribution and wall
      shear stress in a set of 48 in vivo vessel segments. The results were conclusive
      for both studies, with a stronger correlation of circumferential plaque thickness
      with local curvature than with wall shear stress. The inverse relationship
      between local wall shear stress and plaque thickness was significantly more
      pronounced (p<0.025) in vessel cross sections exhibiting compensatory enlargement
      (positive remodeling) without luminal narrowing than when the full spectrum of
      disease severity was considered. The inverse relationship was no longer observed
      in vessels where less than 35% of vessel cross sections remained without luminal
      narrowing. The findings of this study confirm, in vivo, the hypothesis that
      relatively lower wall shear stress is associated with early plaque development.

PMID- 16644263
TI  - Fluorescence enhancement of yttrium(III)-rutin by nucleic acids in the presence
      of cetyltrimethylammonium bromide.
AB  - It is found that nucleic acids can enhance the fluorescence intensity of
      yttrium(III) (Y(3+))-rutin in presence of cetyltrimethylammonium bromide (CTMAB)
      system. In hexamethylenetetramine (HMTA)-HCl buffer, the maximum enhanced
      fluorescence is produced, with maximum excitation and emission wavelengths at 452
      and 520 nm, respectively. Based on this, a new fluorimetric method of
      determination of nucleic acids is proposed. Under optimum conditions, the
      enhanced fluorescence intensity is proportion to the concentration of nucleic
      acids in the range of 1.0 x 10(-7) to 1.0 x 10(-5)g/ml for fish sperm DNA
      (fsDNA), 1.0 x 10(-7) to 4.6 x 10(-6)g/ml for yeast RNA (yRNA), their detection
      limits (S/N=3) are 7.5 x 10(-8), 8.0 x 10(-8)g/ml, respectively. The interaction
      mechanism is also studied.

PMID- 16644264
TI  - Trinuclear lanthanide complexes of a compartmental ligand N,N'-bis(2-pyridinyl)
      2,6-pyridinedicarboxamide: a spectroscopic investigation.
AB  - Trinuclear lanthanide complexes of the formula
      [Ln(3)(PPDA)(NO(3))(6)(H(2)O)(2)].NO(3).2H(2)O where Ln=La(III), Pr(III),
      Sm(III), Nd(III), Eu(III) Gd(III) Tb(III), Dy(III) and Y(III); H(2)PPDA=N,N'
      bis(2-pyridinyl)-2,6-pyridinedicarboxamide, have been isolated. The complexes
      were characterized by elemental analyses, conductivity measurements, magnetic
      susceptibility measurements and spectral (IR, NMR, UV-vis, fluorescence, FAB and
      EPR) and thermal studies.

PMID- 16644265
TI  - Molecular exciton theory calculations based on experimental results for
      Solophenyl red 3BL azo dye-surfactants interactions.
AB  - The influence of anionic surfactant: sodium dodecyl sulfate (SDS) and cationic
      surfactants: cetyltrimethylammonium bromides (C16TAB) and cetylpyridinium
      chloride (CPC) on the electronic spectrum of Solophenyl red 3BL azo dye (C.I.
      Direct 80) in aqueous solution was studied by means of UV-vis spectroscopy.
      Since, Solophenyl red 3BL azo dye was an anionic soluble dye, therefore, did not
      observed any interaction between SDS and 3BL dye. On the other hand, in the case
      of C16TAB, aggregation was reflected by a hyosochromic shift of the main
      absorption band and dye H-aggregation was responsible for the short wavelength
      absorption band. Also, UV-vis spectra showed that micelle formation occurs for
      C16TAB surfactant in 3BL dye aqueous solution in lower concentration in
      comparison with C16TAB in aqueous solution lonely. Micelle formation was
      indicated by a red shift of the whole spectra with respect to monomer location.
      The importance of hydrophobic interactions was revealed by the dependence of
      aggregation on the cationic surfactant structure. Further results showed that dye
      H-aggregation was occurred under the cationic surfactant CPC as well, but in this
      case micelle formation could not occur. Addition of CPC surfactant into the J
      aggregate dye solution in highly acidic aqueous solution was also caused
      completely disaggregating of dimer molecules, which may be related to occuring an
      acid-base reaction between them. Applicability of the molecular exciton (Kasha)
      theory in order to interpret of aggregation results and to estimate dimer
      structure of 3BL dye under C16TAB and CPC surfactants addition was very poor and
      the calculated data based on this model showed that this simple point-dipole
      model could not describe our experimental results.

PMID- 16644266
TI  - Fourier transform-infrared and Raman spectra, ab initio calculations and
      assignments for 6-methyl-4-bromomethylcoumarin.
AB  - Fourier transform-infrared (4000-400 cm-1) and Raman (3500-50 cm-1) spectral
      measurements have been made for 6-methyl-4-bromomethylcoumarin. Equilibrium
      structures, harmonic vibrational frequencies, infrared intensities, and
      depolarization ratios have been computed at RHF/6-31G* and B3LYP/6-31G* levels of
      theory. Twisting CH2Br moiety in the geometry optimization leads to the most
      stable conformer lacking symmetry (C1). This is reflected in the richness of
      bands in the experimental spectra. A complete assignments of the bands, aided by
      the ab initio calculations, has been proposed for the 6-methyl-4
      bromomethylcoumarin. Due to lack of symmetry, several normal vibrations have been
      found to be mixed ones.

PMID- 16644267
TI  - Phosphatidylinositol 3-phosphate recognition and membrane docking by the FYVE
      domain.
AB  - The FYVE domain is a small zinc binding module that recognizes
      phosphatidylinositol 3-phosphate [PtdIns(3)P], a phospholipid enriched in
      membranes of early endosomes and other endocytic vesicles. It is usually present
      as a single module or rarely as a tandem repeat in eukaryotic proteins involved
      in a variety of biological processes including endo- and exocytosis, membrane
      trafficking and phosphoinositide metabolism. A number of FYVE domain-containing
      proteins are recruited to endocytic membranes through the specific interaction of
      their FYVE domains with PtdIns(3)P. Structures and PtdIns(3)P binding modes of
      several FYVE domains have recently been characterized, shedding light on the
      molecular basis underlying multiple cellular functions of these proteins. Here,
      structural and functional aspects and the current mechanism of the multivalent
      membrane anchoring by monomeric or dimeric FYVE domain are reviewed. This
      mechanism involves stereospecific recognition of PtdIns(3)P that is facilitated
      by non-specific electrostatic contacts and modulated by the histidine switch, and
      is accompanied by hydrophobic insertion. Contributions of each component to the
      FYVE domain specificity and affinity for PtdIns(3)P-containing membranes are
      discussed.

PMID- 16644268
TI  - Wiggling ears: an unusual EEG artifact caused by muscle activity.

PMID- 16644269
TI  - Test-retest reproducibility of 50 kHz linear-electrical impedance myography.
AB  - OBJECTIVE: Electrical impedance myography (EIM) is a method for evaluating muscle
      in which high-frequency, low-intensity alternating current is applied to a body
      region and the resulting surface voltage pattern over a muscle of interest is
      measured. In this study, the reproducibility for the simplest of these
      techniques, 50 kHz linear-EIM, was assessed for three muscles. METHODS: Fifty
      kilohertz linear-EIM was performed on the biceps, quadriceps, and tibialis
      anterior of 30 normal subjects ranging in age from 21 to 90 years, and the major
      outcome variable, the spatially averaged phase (thetaavg), measured. The
      measurements were repeated within 250 days and comparisons between the two data
      sets made. RESULTS: Reproducibility, as measured by the intraclass correlation
      coefficients for all three muscles, was very high at 0.970, 0.971, and 0.938 for
      biceps, quadriceps, and tibialis anterior, respectively. Variability between
      measurements was on average 4.2% for all muscle combined, with an upper limit of
      16.8%. CONCLUSIONS: Fifty kilohertz linear-EIM demonstrates excellent test-retest
      reproducibility. SIGNIFICANCE: These results support the view that 50 kHz linear
      EIM has the potential to be used as a simple, fast, and non-invasive measurement
      for the assessment of disease status, either as part of individual patient care
      or as a surrogate outcome measure in clinical trials work.

PMID- 16644270
TI  - Automated single-trial measurement of amplitude and latency of laser-evoked
      potentials (LEPs) using multiple linear regression.
AB  - OBJECTIVE: Laser stimulation of Adelta-fibre nociceptors in the skin evokes
      nociceptive-specific brain responses (laser-evoked potentials, LEPs). The largest
      vertex complex (N2-P2) is widely used to assess nociceptive pathways in
      physiological and clinical studies. The aim of this study was to develop an
      automated method to measure amplitudes and latencies of the N2 and P2 peaks on a
      single-trial basis. METHODS: LEPs were recorded after Nd:YAP laser stimulation of
      the left hand dorsum in 7 normal volunteers. For each subject, a basis set of 4
      regressors (the N2 and P2 waveforms and their respective temporal derivatives)
      was derived from the time-averaged data and regressed against every single-trial
      LEP response. This provided a separate quantitative estimate of amplitude and
      latency for the N2 and P2 components of each trial. RESULTS: All estimates of LEP
      parameters correlated significantly with the corresponding measurements performed
      by a human expert (N2 amplitude: R2=0.70; P2 amplitude: R2=0.70; N2 latency:
      R2=0.81; P2 latency: R2=0.59. All P<0.0001). Furthermore, regression analysis was
      able to extract an LEP response from a subset of the trials that had been
      classified by the human expert as without response. CONCLUSIONS: This method
      provides a simple, fast and unbiased measurement of different components of
      single-trial LEP responses. SIGNIFICANCE: This method is particularly desirable
      in several experimental conditions (e.g. drug studies, correlations with
      experimental variables, simultaneous EEG/fMRI and low signal-to-noise ratio data)
      and in clinical practice. The described multiple linear regression approach can
      be easily implemented for measuring evoked potentials in other sensory
      modalities.

PMID- 16644271
TI  - Source localization of small sharp spikes: low resolution electromagnetic
      tomography (LORETA) reveals two distinct cortical sources.
AB  - OBJECTIVE: We have investigated the cortical sources and electroencephalographic
      (EEG) characteristics of small sharp spikes (SSS) by using statistical non
      parametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA).
      METHODS: We analyzed 7 SSS patterns (501 individual SSS) in 6 patients who
      underwent sleep EEG studies with 29 or 23 scalp electrodes. The scalp signals
      were averaged time-locked to the SSS peak activity and subjected to SNPM of
      LORETA values. RESULTS: All 7 SSS patterns (mean 72 individual SSS, range 11-200)
      revealed a very similar and highly characteristic transhemispheric oblique scalp
      voltage distribution comprising a first negative field maximum over ipsilateral
      lateral temporal areas, followed by a second negative field maximum over the
      contralateral subtemporal region approximately 30 ms later. SNPM-LORETA
      consistently localized the first component into the ipsilateral posterior insular
      region, and the second component into ipsilateral posterior mesial temporo
      occipital structures. CONCLUSIONS: SSS comprise an amalgam of two sequential,
      distinct cortical components, showing a very uniform and peculiar EEG pattern and
      cortical source solutions. As such, they must be clearly distinguished from
      interictal epileptiform discharges in patients with epilepsy. SIGNIFICANCE: The
      awareness of these peculiar EEG characteristics may increase our ability to
      differentiate SSS from interictal epileptiform activity. The finding of a
      posterior insular source might serve as an inspiration for new physiological
      considerations regarding these enigmatic waveforms.

PMID- 16644272
TI  - Predictability of the target stimulus for sensory-guided movement modulates early
      somatosensory cortical potentials.
AB  - OBJECTIVE: To investigate the role of sensory modulation in the control of
      sensory-guided behaviour. Specifically, we hypothesized that early somatosensory
      evoked potentials (SEPs) would be facilitated during performance of continuous
      sensory-guided movement requiring sustained attention. METHODS: Median nerve SEPs
      were elicited via electrical stimulation and recorded from scalp electrodes while
      subjects performed tasks requiring continuous sensory-motor transformations.
      Subjects received a predictable (rhythmic amplitude modulation) or unpredictable
      (random amplitude modulation) amplitude varying tactile stimulus (frequency
      constant at 20 Hz) delivered to the tip of the index finger either alone or with
      the requirement to track it by modulating the isometric grip force produced by
      the opposite hand. RESULTS: Early SEP (N20-P27) amplitudes were differentially
      modulated during unpredictable tracking compared to sensory-motor controls.
      Specifically, N20 amplitudes were attenuated and P27 amplitudes were enhanced
      during sensory-guided tracking. CONCLUSIONS: Sustained attention to task-relevant
      sensory stimuli differentially modulates areas within primary somatosensory
      cortex (S1) during a continuous sensory-motor transformation. SIGNIFICANCE: These
      data have implications for understanding the role of attention in regulating
      somatosensory cortices during sensory-motor behaviour.

PMID- 16644273
TI  - Predicted current densities in the brain during transcranial electrical
      stimulation.
AB  - OBJECTIVE: We sought an electrical modeling approach to evaluate the potential
      application of finite element method (FEM) modeling to predict current pathways
      and intensities in the brain after transcranial electrical stimulation. METHODS:
      A single coronal MRI section through the head, including motor cortex, was
      modeled using FEM. White matter compartments with both anatomically realistic
      anisotropies in resistivity and with a homogeneous resistivity were modeled.
      Current densities in the brain were predicted for electrode sites on the scalp
      and after theoretical application of a conductive head restraint device. RESULTS:
      Localized current densities were predicted for the model with white matter
      anisotropies. Differences in predicted peak current densities were related to
      location of stimulation sites relative to deep sulci in the brain and scalp
      shunting that was predicted to increase with inter-electrode proximity. A
      conductive head restraint device was predicted to shunt current away from the
      brain when a constant current source was used. CONCLUSIONS: The complex geometry
      of different tissue compartments in the head and their contrasting resistivities
      may jointly determine the strength and location of current densities in the brain
      after transcranial stimulation. This might be predictable with FEM incorporating
      white matter anisotropies. Conductive head restraint devices during surgery may
      be contraindicated with constant current stimulation. SIGNIFICANCE: Individually
      optimized tcMEP monitoring and localized transcranial activation in the brain
      might be possible through FEM modeling.

PMID- 16644274
TI  - Automated neonatal seizure detection.

PMID- 16644275
TI  - Postural adaptation to walking on inclined surfaces: II. Strategies following
      spinal cord injury.
AB  - OBJECTIVE: To investigate the postural adaptations to inclined walking in spinal
      cord injured (SCI) subjects. METHODS: Eight subjects with an incomplete spinal
      cord injury and eight age- and sex-matched healthy control subjects walked on a
      treadmill at five different grades (from -10 to 10%) without any assistance. The
      movements of the trunk and pelvis were recorded with four high-resolution
      cameras. RESULTS: The SCI subjects walked with greater forward tilt of both trunk
      and pelvic segments during level or inclined walking and could not adapt their
      body orientation to the inclination of the support surface as observed in healthy
      control subjects. Trunk and pelvic rotations as well as lateral excursions were
      maintained constant during inclined walking in both groups of subjects but total
      excursions were always greater in the SCI subjects. CONCLUSIONS: We argue that
      the forward bending posture observed in SCI subjects at any treadmill grade is
      adopted to compensate for a certain degree of instability due to lower-limb
      deficits and is a postural adaptation to the daily use of ambulatory assistive
      devices. SIGNIFICANCE: The bent posture adopted by SCI subjects is not adequate
      when performing level or downhill walking and can lead to a loss of balance or a
      fall in these subjects.

PMID- 16644276
TI  - Involvement of the human cerebellum in short-term and long-term habituation of
      the acoustic startle response: a serial PET study.
AB  - OBJECTIVE: Numerous studies have shown an involvement of the human cerebellum in
      motor learning, but little is known about the role of the cerebellum in learning
      of unspecific aversive reactions. The present study sought to distinguish which
      areas of the human cerebellum and brain-stem are involved in short-term
      habituation (STH) and long-term habituation (LTH) of the acoustic startle
      response. METHODS: On 5 consecutive days 42 acoustic startle stimuli were applied
      each day in 8 male healthy subjects. On the first and on the fifth day of the
      experiment [15O]H2O PET scans were performed. RESULTS: Electromyographic
      recordings revealed a significant decrease of the startle response within each
      day (STH) and across the 5 days of the experiment (LTH). On both days a decrease
      of regional cerebral blood flow (rCBF) across PET scans was found in the medial
      cerebellum most probably reflecting reduced sensory feedback during STH. Between
      days an increase of rCBF in the dorsomedial pons, in the mesencephalon and in an
      area of the medial cerebellum was observed. These activations may reflect
      increased inhibition of the startle response during LTH and correspond to
      previous animal lesion studies. Furthermore, during LTH an increase of rCBF
      within the lateral cerebellum in lobule HVI/Crus I was detected. CONCLUSIONS:
      These results suggest that distinct parts of the medial and lateral cerebellum
      are involved in habituation of the acoustic startle response. Lobule HVI/Crus I
      most likely plays a more general role in implicit learning processes considering
      its involvement in several conditioning paradigms. SIGNIFICANCE: The results of
      the present study contribute to the understanding of cerebellar involvement in
      learning of unspecific aversive reactions.

PMID- 16644277
TI  - Homeostatic effects of plasma valproate levels on corticospinal excitability
      changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy.
AB  - OBJECTIVE: The preliminary results of noninvasive brain stimulation for epilepsy
      treatment have been encouraging, but mixed. Two important factors may contribute
      to this heterogeneity: the altered brain physiology of patients with epilepsy and
      the variable presence of antiepileptic drugs. Therefore, we aimed to study the
      effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile
      myoclonic epilepsy (JME) in two different conditions: low- or high-plasma
      valproate levels. METHODS: Fifteen patients with JME and 12 age-matched healthy
      subjects participated in this study. Corticospinal excitability before and after
      1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate
      levels; and these results were compared with those in healthy subjects. RESULTS:
      In patients with chronic use of valproate and low-plasma concentrations, 1 Hz
      rTMS had a similar significant inhibitory effect on corticospinal excitability as
      in healthy subjects. However, in the same patients when the serum valproate
      concentration was high, 1 Hz rTMS increased the corticospinal excitability
      significantly. In addition, there was a significant positive correlation between
      plasma valproate levels and the motor threshold changes after 1 Hz rTMS.
      CONCLUSIONS: Our findings can be accounted for by mechanisms of homeostatic
      plasticity and illustrate the dependency of the modulatory effects of rTMS on the
      physiologic state of the targeted brain cortex. SIGNIFICANCE: The therapeutic use
      of rTMS in epilepsy should take into consideration the interaction between rTMS
      and drugs that change cortical excitability.

PMID- 16644278
TI  - Absent event-related potential (ERP) word repetition effects in mild Alzheimer's
      disease.
AB  - OBJECTIVE: We hypothesized that an ERP word repetition paradigm, which reliably
      elicits and modulates the P600 and N400 components, would be particularly
      sensitive to the memory deficits and altered synaptic plasticity in mild
      Alzheimer's disease (AD). The P600 (a late positive component, or 'LPC'), and the
      N400, are sensitive indices of memory encoding and semantic processing,
      respectively. METHODS: We studied 11 patients with mild AD (mean MMSE=22.9) and
      11 elderly (mean age=77.1) normal controls (NC) on a paradigm in which
      semantically 'congruous' category statement/exemplar pairs (50%) and
      'incongruous' category statement/non-exemplar pairs (50%) repeat at 10-140 s
      intervals. A minimum of 19 channels ERP data were recorded and submitted to split
      plot ANOVAs. RESULTS: Normal ERP data showed: (1) a significant word repetition
      effect for congruous words, with a wide-spread late positivity between
      approximately 300 and 800 ms post-stimulus (P600) that is larger for New than Old
      words; (2) a significant N400 repetition effect for incongruous words, with a
      right posterior negativity that is reduced for Old relative to New words. By
      contrast, neither of these word repetition effects was reliably present in the
      mild AD group. Good group discrimination was achieved by requiring that both
      these repetition effects were > or = the 10th percentile, with 100% sensitivity
      and 82% specificity. CONCLUSIONS: We found significant abnormalities of the N400
      and P600 in mild AD, with both potentials showing markedly reduced sensitivity to
      word repetition. SIGNIFICANCE: The absence of normal N400 and LPC/P600 word
      repetition effects suggests impaired functioning of their neural generators,
      several of which are located in medial temporal lobe predilection sites (e.g.
      anterior fusiform, parahippocampal gyrus, hippocampus) for AD/tau pathology.

PMID- 16644279
TI  - Normative values calculated with the inverse Gaussian and the lognormal
      distributions.

PMID- 16644280
TI  - The sigmaB regulon in Staphylococcus aureus and its regulation.
AB  - The Staphylococcus aureus genome codes for a sigma factor that shows close
      sequence similarity to the alternative sigma factor sigmaB of Bacillus subtilis.
      However, of the proteins controlling the activity of sigmaB in B. subtilis only
      RsbU, RsbV, and RsbW are encoded in the staphylococcal genome. Therefore, the
      regulation of the sigmaB activity must differ between these two bacterial
      species. The present study was designed (i) to describe the sigmaB regulon and
      (ii) to identify stimuli leading to an activation of sigmaB-dependent
      transcription. All conditions under which sigmaB was activated in S. aureus (heat
      shock, addition of MnCl2 or NaCl, alkaline shock) required the presence of RsbU,
      a positive regulator of sigmaB. In contrast to B. subtilis, a drop in the
      cellular ATP level caused by the addition of carbonyl cyanide m
      chlorophenylhydrazone did not lead to an activation of sigmaB in S. aureus.
      Moreover, ethanol, a strong inductor of sigmaB activity in B. subtilis, also
      failed to induce sigmaB in S. aureus. Expression of sigB and sigmaB-dependent
      genes was enhanced following entry into stationary phase of cells grown in
      complex medium (LB medium). Our DNA microarray data indicated that 122 genes are
      positively regulated by sigmaB under alkaline stress conditions. Interestingly,
      only 12% of these genes have an orthologue in the B. subtilis sigmaB regulon,
      suggesting that the function of the sigmaB regulon in S. aureus is different from
      that in B. subtilis. We could show that sigmaB of S. aureus, in contrast to B.
      subtilis, may have a function in more basic cellular processes such as cell
      envelope composition, membrane transport processes and intermediary metabolism.
      sigmaB-dependent genes identified by the DNA microarray approach were subjected
      to detailed transcriptional analyses using primer extension and Northern blot
      techniques. These analyses confirmed our DNA microarray data and furthermore
      revealed different regulatory groups of sigmaB-dependent genes.

PMID- 16644281
TI  - Determinants of aflatoxin levels in Ghanaians: sociodemographic factors,
      knowledge of aflatoxin and food handling and consumption practices.
AB  - Aflatoxins are among the most potent of carcinogens found in staple foods such as
      groundnuts, maize and other oil seeds. This study was conducted to measure the
      levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1)
      (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming
      region of Ghana and to examine the association between aflatoxin levels and
      several socio-demographic factors and food handling and consumption practices. A
      cross-sectional study was conducted in four villages in the Ejura Sekyedumase
      district of Ghana. A socio-demographic survey was administered to 162
      participants. Blood samples were collected from 140 and urine samples from 91 of
      the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in
      urine were measured. High AFB(1) albumin-adduct levels were found in the plasma
      (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg;
      median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/
      2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg;
      median=472.67pg/mg) of most of the participants. There was a statistically
      significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in
      plasma and AFM(1) levels in urine. Several socio-demographic factors, namely,
      educational level, ethnic group, the village in which participants lived, number
      of individuals in the household, and number of children in the household
      attending secondary school, were found to be significantly associated with AFB(1)
      albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic
      group (p=0.04), the village in which participants live (p=0.02), and the number
      of individuals in the household (p=0.01), were significant predictors of high
      AFB(1) albumin-adducts. These findings indicate strongly that there is need for
      specifically targeted post-harvest and food handling and preparation
      interventions designed to reduce aflatoxin exposure among the different ethnic
      groups in this region of Ghana.

PMID- 16644282
TI  - The situation of tuberculosis and tuberculosis control in animals of economic
      interest.
AB  - The need to focus international attention on the continuing problem of
      tuberculosis in animals of economic interest, can hardly be over-emphasized.
      Mycobacterium bovis, is the most universal pathogen among the mycobacteria and
      produces progressive disease in most domestic animals (especially those of
      economic interest) and in humans. The prevalence of animal tuberculosis
      therefore, has relevance for both human and veterinary medical practitioners and
      decision makers on the strategic approach to be adopted in the control of the
      disease. There is the tendency to underestimate the ability of M. bovis to
      produce tuberculosis or to assume that it has been totally eliminated and that
      potential exposure to this pathogen may be a remote occurrence. This perception
      could have a direct implication for the control of the disease at source, that is
      in domestic animals. The current epidemic of human immunodeficiency virus (HIV)
      infection raises the issue of what future impact this epidemic may have if the
      incidence of M. bovis infection in humans increases, when control in livestock
      especially cattle, is neglected by both developed and developing countries.

PMID- 16644283
TI  - Expression of tuberculosis antigen ESAT-6 in Nicotiana tabacum using a potato
      virus X-based vector.
AB  - A good candidate antigen to create a therapeutic vaccine against TB is the ESAT-6
      protein. Antigens produced in plants have already been successfully used as
      experimental vaccines, and small single-stranded RNA plant viruses have emerged
      as promising tools to rapidly express large amounts of foreign proteins in
      susceptible host plants. Here, we present the expression of ESAT-6 protein in
      Nicotiana tabacum using a vector based on potato virus X (PVX). The complete ESAT
      6 open reading frame is expressed as a fusion protein with the 2A peptide of Foot
      and Mouth Disease Virus and the amino terminal of the PVX coat protein (CP)
      (PVXESAT-6). This strategy allows the production of free CP and ESAT-6 as well as
      fused ESAT-2A-CP to obtain recombinant chimaeric virions expressing ESAT-6 at the
      surface to be used as particulate antigen in vaccination. ESAT-6 expression was
      tested in agroinfiltrated tobacco leaves and products of the expected molecular
      masses corresponding to cleaved CP and ESAT-2A-CP fusion protein were observed,
      with ESAT-6 yields ranging from 0.5% to 1% of total soluble protein. Our study
      describes for the first time the expression of the ESAT-6 protein in tobacco
      plants using a PVX-derived vector. This strategy should serve as a convenient,
      rapid, low-cost expression system and can also be used for the assessment of ESAT
      6 production and function prior to stable plant transformation.

PMID- 16644284
TI  - Detecting genetic variability among different Mycobacterium tuberculosis strains
      using DNA microarrays technology.
AB  - Recent advances in functional and comparative genomics have improved our
      understanding of genetic diversity among the Mycobacterium tuberculosis complex.
      In this study, we investigated the genetic polymorphism of M. tuberculosis using
      whole-genome microarray analysis. Amplified fragments of 15 M. tuberculosis
      strains (from two different geographical origins) and the reference strain H37Rv
      were produced by random amplification of polymorphic DNA (RAPD) using three
      different primers. The RAPD products were labeled with fluorescent dyes (Cy3 and
      Cy5) and hybridized to a TB DNA microarray representing nearly all open reading
      frames (ORFs) of H37Rv. The final results were analyzed using bioinformatic
      tools. Some genetic variability was found among the 16 M. tuberculosis strains.
      The majority of the highly polymorphic DNA sequences were observed in ORFs
      representing non-essential genes of the bacterium. The future use of comparative
      genomics based on DNA microarray technology should prove a powerful tool for
      understanding phenotypic variability among M. tuberculosis isolates of similar
      genetic composition. It is also a promising approach to provide important
      insights into evolution, virulence and pathogenesis of M. tuberculosis.

PMID- 16644285
TI  - Streptomyces as host for recombinant production of Mycobacterium tuberculosis
      proteins.
AB  - The 45/47 kDa APA protein (Rv1860) of Mycobacterium tuberculosis was produced by
      Streptomyces lividans. The recombinant protein could be recovered from the
      culture medium of an S. lividans clone containing the apa gene under control of
      the promoter and signal sequence of the Streptomyces coelicolor agarase gene. The
      recombinant protein production was further scaled-up using fermentation
      conditions. The APA protein was subsequently purified from the culture
      supernatant by means of immunochromatography. About 80 mg of recombinant protein
      were obtained per liter of culture media. In vivo tests with the APA protein
      purified from S. lividans TK24/pRGAPA1 revealed that the recombinant protein was
      antigenic and could induce high titers of specific antibodies in the mouse
      biological model. Results obtained concerning heterologous production of APA, its
      immunogenic and antigenic capacity, demonstrated the potential of S. lividans as
      a valuable host for the production of recombinant proteins from M. tuberculosis.

PMID- 16644286
TI  - Dimensions of the Somatic Health Complaints Questionnaire (SHCQ) in a sample of
      myocardial infarction patients.
AB  - A short health complaints measure may provide information on the degree of
      recovery from acute myocardial infarction. The present study therefore evaluated
      a questionnaire-called the Somatic Health Complaints Questionnaire (SHCQ)-that
      includes 13 items concerning health problems common in cardiac patients. The
      sample included 114 patients in total, 37 women and 77 men, who had suffered a
      first-time myocardial infarction 5months prior to the testing. Confirmatory
      factor analysis was performed to examine whether the factor structure replicated
      the hypothesized hierarchical model. The results indicated that SHCQ represents
      four dimensions: breathlessness, fatigue, pain and unrest. It was also found that
      SHCQ may be treated as one general concept. It is a brief and easily administered
      questionnaire and may therefore be a useful tool in secondary prevention work,
      identifying patients at risk for possible negative consequences of a first-time
      myocardial infarction.

PMID- 16644287
TI  - Analysis of human sera that are polyreactive in an addressable laser bead
      immunoassay.
AB  - BACKGROUND: Following the introduction of addressable laser bead immunoassays
      (ALBIA) into our clinical laboratory, it was noted that certain sera would
      exhibit reactivity to numerous antigens in the array. To further understand the
      nature of this reactivity, we analyzed the reactivity of sequential sera that
      were identified over a 1 year period. METHODS: Sera that demonstrated reactivity
      to 6 or more of the 8 antigens in an ALBIA kit (QuantaPlex 8: chromatin, Sm, RNP,
      Scl-70, ribosomal P protein, SS-A/Ro, SS-B/La, Jo-1) were tested for
      autoantibodies by indirect immunofluorescence (IIF) on HEp-2 cell substrates, for
      IgG, IgM and IgA rheumatoid factor, chromatin and ribosomal P protein by ELISA
      and by LINE immunoassay (LIA) and immunoblotting (IB). RESULTS: In one calendar
      year, 40/4096 (0.8%) sera analyzed in a routine clinical laboratory setting
      demonstrated reactivity to 6 or more antigens in the QuantaPlex 8 kits. There was
      no common IIF pattern that could be attributed to the polyreactive sera. There
      was no apparent correlation of polyreactivity with IIF titers, indeed, 4/40 (10%)
      sera had a negative ANA at the screening dilution of 1/160. When subjected to IB,
      LIA and ELISA, polyreactivity to three or more antigens was confirmed for 12/40
      (30%) of sera while 8/40 (20%) had reactivity to 1-2 antigens and 20 (50%) did
      not react with any antigens in these assays. Overall agreement of positive or
      negative tests between the ALBIA and IB, LIA and ELISA was 75% for chromatin, 50%
      for SS-A, 27.5% for Sm, 25% for Rib-P, 22.5% for RNP, 20% for Scl-70, 15% for Jo
      1 and 7.5% for SS-B. 17/40 (42.5%) had a positive IgM, IgG or IgA rheumatoid
      factor, and 12/40 (30%) had all three isotype rheumatoid factors. CONCLUSIONS: On
      average, the agreement between ALBIA and other assays in this study of
      polyreactive sera was 30%. Approximately, one-half of sera that demonstrate
      reactivity to multiple autoantigens in a commercial ALBIA were confirmed to have
      reactivity to at least one autoantigen in another diagnostic assay and 30% could
      be regarded as polyreactive. Other sera, some of which had rheumatoid factor,
      appeared to have high background binding without demonstrating specific binding
      to any of the cognate antigens.

PMID- 16644288
TI  - Modulation of the systemic inflammatory response by recombinant human interleukin
      11: a prospective randomized placebo controlled clinical study in patients with
      hematological malignancy.
AB  - The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11)
      were investigated in a clinical trial among patients with hematological
      malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy.
      Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were
      measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients
      receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3
      1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days
      [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days
      without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A
      similar pattern in CRP concentrations was observed. Multivariate analysis
      indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of
      infectious episodes and other factors. 7 patients (all receiving placebo) of 40
      had elevated TNFalpha levels. IL-6 and IL-8 levels were not substantially
      affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin
      (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in
      dampening the deleterious effects of a hyperactive TNFalpha environment, rhIL-11
      induced upregulation of sTNFRI shedding is a potentially important mechanism for
      modulating immune and inflammatory responses in humans.

PMID- 16644289
TI  - Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by
      ocular subretinal injection.
AB  - AAV2 delivery of the RPE65 gene to the retina of blind RPE65-deficient animals
      restores vision. This strategy is being considered for human trials in RPE65
      associated Leber congenital amaurosis (LCA), but toxicity and dose efficacy have
      not been defined. We studied ocular delivery of AAV-2/2.RPE65 in RPE65-mutant
      dogs. There was no systemic toxicity. Ocular examinations showed mild or moderate
      inflammation that resolved over 3 months. Retinal histopathology indicated that
      traumatic lesions from the injection were common, but thinning within the
      injection region occurred only at the two highest vector doses. Biodistribution
      studies at 3 months postinjection showed no vector in optic nerve or visual
      centers in the brain and only isolated non-dose-related detection in other
      organs. We also performed biodistribution studies in normal rats at about 2 weeks
      and 2 months postinjection and vector was not widespread outside the injected
      eye. Dose-response results in RPE65-mutant dogs indicated that the highest 1.5
      log unit range of vector doses proved efficacious. The efficacy and toxicity
      limits defined in this study lead to suggestions for the design of a subretinal
      AAV-2/2.RPE65 human trial of RPE65-associated LCA.

PMID- 16644290
TI  - Bioenergetics of aging and calorie restriction.
AB  - Aging is a physiological process that involves a multi-factorial set of
      deleterious changes. These alterations are caused by an exponential increase in
      damage to macromolecules. This process is likely due to the cumulative effects of
      oxidative stress over time. One area of ongoing research in gerontology has
      focused on determining why there is an age-dependent decrease in cellular
      bioenergetics. The aim of this review is to summarize the recent findings on the
      effects of aging and calorie restriction on energy metabolism. The effect of
      calorie restriction on age-associated changes in bioenergetic parameters will be
      examined.

PMID- 16644291
TI  - Genetic dissection of vertebrate 53BP1: a major role in non-homologous end
      joining of DNA double strand breaks.
AB  - 53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly
      recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in
      the DNA damage response, we generated 53BP1(-/-) cells from the chicken DT40 cell
      line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to
      ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in
      mammalian cells, DT40 53BP1(-/-) cells had normal intra S phase and G2/M
      checkpoints. G1 specific radiosensitivity and a higher sensitivity to
      topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in
      DT40 53BP1(-/-) cells. Genetic analyses confirm this suggestion as we have
      demonstrated an epistatic relationship between 53BP1 and the NHEJ genes, Ku70 and
      Artemis, but not with Rad54, a gene essential for repair of DSBs by homologous
      recombination. We conclude that the major role of 53BP1 in supporting survival of
      DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ.

PMID- 16644292
TI  - Defining the salt effect on human RAD51 activities.
AB  - Previous work by Sung and colleagues identified unusual salt requirements for
      hRAD51 strand exchange compared to RecA [S. Sigurdsson, K. Trujillo, B. Song, S.
      Stratton, P. Sung, Basis for avid homologous DNA strand exchange by human Rad51
      and RPA, J. Biol. Chem. 276 (2001) 8798-8806]. Later studies showed that this
      salt [(NH4)2SO4] appeared to enhance the ability of hRAD51 to distinguish ssDNA
      from dsDNA [Y. Liu, A.Z. Stasiak, J.Y. Masson, M.J. McIlwraith, A. Stasiak, S.C.
      West, Conformational changes modulate the activity of human RAD51 protein, J.
      Mol. Biol. 337 (2004) 817-827]. The mechanism of this salt effect remains
      enigmatic. Here, we detail the properties of several neutral salts on hRAD51
      activities. We found that the cation identity correlated with the stimulatory
      effect of these neutral salts on hRAD51 ATPase and strand exchange activities.
      The salt effect appears to be related to the size of the cation, which may be
      largely mimicked with the cesium ion. These results are consistent with the
      hypothesis that stimulating cations induce an important conformation and/or
      transition state in hRAD51. In the presence of an optimal ammonium-based salt
      (NaNH4HPO4), hRAD51 mediated strand exchange was successfully performed using a
      simplified protocol. We confirmed and extend the observation that efficient
      strand exchange correlated with preferential binding of ssDNA over dsDNA. In
      addition we observed an induced stability of the hRAD51-DNA complex in the
      presence of ATP that becomes unstable following ATP hydrolysis (the ADP form or
      nucleotide free form). These salt-induced characteristics of hRAD51 increasingly
      resemble RecA-mediated recombinase activities, which should help in dissecting
      the mechanism of these proteins in homologous recombination.

PMID- 16644293
TI  - Features of the milk whey protein partitioning in polyethyleneglycol-sodium
      citrate aqueous two-phase systems with the goal of isolating human alpha-1
      antitrypsin expressed in bovine milk.
AB  - Partitioning behaviour of the bovine whey proteins (bovine serum albumin, alpha
      lactoalbumin and beta-lactoglobulin) and human alpha-1 antitrypsin in aqueous two
      phase systems prepared with polyethyleneglycol (molecular masses: 1000, 1450 and
      3350)-sodium citrate was analysed at pH 5.2, 6.2 and 8.2. Alpha lactoalbumin
      concentrated in the polyethyleneglycol rich-phase, while beta-lactoglobulin,
      bovine serum albumin and alpha-1 antitrypsin showed affinity for the citrate rich
      phase. In aqueous two-phase systems of high medium pH and high polyethyleneglycol
      molecular mass the protein partitioning equilibrium is displaced to the citrate
      rich-phase. The polyethyleneglycol 1450-pH 5.2 system with a top/bottom phase
      volume ratio of 3 showed to have the best capability of recovering the alpha-1
      antitrypsin from a mixture prepared with natural milk whey and human alpha-1
      antitrypsin. The recovery of this protein in the bottom phase was of 90% and the
      purity of the obtained product was of 98%. The method appears to be suitable as a
      starting point to isolate other human proteins expressed in transgenic bovine
      milk.

PMID- 16644294
TI  - Sensitive microanalysis of gabapentin by high-performance liquid chromatography
      in human serum using pre-column derivatization with 4-chloro-7-nitrobenzofurazan:
      Application to a bioequivalence study.
AB  - Most of the published methods for analysis of gabapentin, an antiepileptic agent,
      in human serum require automated o-phthalaldehyde derivatization of the drug and
      immediate injection of the unstable derivatives formed. A new, very sensitive and
      simple high-performance liquid chromatographic method for quantitation of the
      drug in human serum using 4-chloro-7-nitrobenzofurazan (NBD-Cl) as a fluorescent
      labeling agent is presented. In this method the sensitivity was significantly
      improved and the limit of quantification of 0.002 microg/ml was obtained using
      100 microl serum sample and 10 microl injection. However, the LOQ can be improved
      by increasing the sampling volume. The procedure involved protein precipitation
      of serum by acetonitrile followed by derivatization with NBD-Cl. Amlodipine was
      used as internal standard and chromatographic separation was performed on a
      Shimpack CLC-C18 (150 mm x 4.6 mm) column. The fluorescence derivative of the
      drug was monitored at excitation and emission wavelengths of 470 and 537 nm,
      respectively. A mobile phase consisting of methanol and sodium phosphate buffer
      (0.05 M; pH 2.5) containing 1 ml/l triethylamine (65:35, v/v) was used. The
      calibration curve was linear over the concentration range of 0.002-15 microg/ml.
      No interferences were found from commonly co-administrated antiepileptic drugs.
      The method was applied in a randomized cross-over bioequivalence study of two
      different gabapentin preparations in 24 healthy volunteers.

PMID- 16644295
TI  - Characterization of the stability of a fully human monoclonal IgG after prolonged
      incubation at elevated temperature.
AB  - The susceptible degradation sites of therapeutic proteins are routinely assessed
      under accelerated conditions such as exposure to chemicals or incubation at
      elevated temperature or a combination of both. A fully human monoclonal IgG(1)
      antibody was characterized after incubation at 40 degrees C for 6 months by
      employing mass spectrometry and chromatography analyses. It was found that
      deamidation, fragmentation and N-terminal glutamate cyclization to form
      pyroglutamate are the major degradation pathways. Three major deamidation sites
      were identified and one site in a small tryptic peptide accounted for more than
      80% of the total. Peptide cleavage was observed at several positions between
      different pairs of amino acids. Most of the cleavage sites were located in the
      hinge or other flexible regions of the IgG molecule.

PMID- 16644296
TI  - Relationship between risk factors and QUS in a European Population: The OPUS
      study.
AB  - There are many risk factors associated with low bone mineral density.
      Quantitative ultrasound (QUS) is a generally accepted method for measurement of
      bone and has been shown to be strongly associated with future fracture risk. The
      Osteoporosis and Ultrasound Study (OPUS) is a multi-centre European wide study
      examining 5 different QUS scanners (4 calcaneal, 1 finger device). The aim of
      this paper was to examine the relationship between risk factors (as assessed by
      questionnaire) and QUS measurements. 449 younger women (aged 20 to 39 years) and
      2283 older women (aged 55 to 79 years) were included in this analysis. As
      expected, those with a self-reported previous fracture had lower QUS measurements
      than those without (P < 0.001). However, no significant difference was seen
      between those reporting a maternal hip fracture and those who did not report such
      an event. Differences were found for smokers vs. non-smokers for SOS but not for
      BUA measurements. Weight was positively correlated with all BUA variables but
      only with some SOS variables. We determined which risk factors were most strongly
      associated with QUS measurements by using step-wise multiple regression. Models
      for each QUS measurement were calculated, and the R2 values ranged from 0.18 to
      0.28 for SOS, 0.27 to 0.32 for BUA and 0.31 to 0.42 for the finger QUS device.
      The most common risk factors across all models were age, use of hormone
      replacement therapy, self-reported previous fracture, self-reported diagnosis of
      osteoporosis, current weight, pulse rate and self-reported estimated height at
      age 20 years. We analysed relationships across the 5 centres and detected some
      geographical differences in the prevalence of the risk factors. In conclusion,
      similar relationships are seen with QUS measurements as are found for bone
      mineral density. However, the strength of the association is dependent on the
      type of QUS device and variable measured.

PMID- 16644297
TI  - Strength of cancellous bone trabecular tissue from normal, ovariectomized and
      drug-treated rats over the course of ageing.
AB  - Hormone therapy (HT) drugs and bisphosphonates prevent osteoporosis by inhibiting
      osteoclastic bone resorption. However, the effects of osteoporosis and anti
      resorptive drugs on the mechanical behavior of the bone tissue constituting
      individual trabeculae have not yet been quantified. In this study, we test the
      hypothesis that the mechanical properties of bone trabecular tissue will differ
      for normal, ovariectomized and drug-treated rat bones over the course of ageing.
      Microtensile testing is carried on individual trabeculae from tibial bone of
      ovariectomized (OVX) rats, OVX rats treated with tibolone and placebo-treated
      controls. The method developed minimizes errors due to misalignment and stress
      concentrations at the grips. The local mineralization of single trabeculae is
      compared using micro-CT images calibrated for bone mineral content assessment.
      Our results indicate that ovariectomy in rats increases the stiffness, yield
      strength, yield strain and ultimate stress of the mineralized tissue constituting
      trabecular bone relative to normal; we found significant differences (P < 0.05)
      at 14, 34 and 54 weeks of treatment. These increases are complemented by a
      significant increase in the mineral content at the tissue level, although overall
      bone mineral density and mass are reduced. With drug treatment, the properties
      remain at, or slightly below, the placebo-treated controls levels for 54 weeks.
      The higher bone strength in the OVX group may cause the trabecular architecture
      to adapt as seen during osteopenia/osteoporosis, or alternately it may compensate
      for loss of trabecular architecture. These findings suggest that, in addition to
      the effects of osteoporosis and subsequent treatment on bone architecture, there
      are also more subtle processes ongoing to alter bone strength at the tissue
      level.

PMID- 16644298
TI  - Transgenic mice with osteoblast-targeted insulin-like growth factor-I show
      increased bone remodeling.
AB  - To determine the effects of locally-expressed insulin-like growth factor (IGF-I)
      on bone remodeling, a transgene was produced in which murine IGF-I cDNA was
      cloned downstream of a gene fragment comprising 3.6 kb of 5' upstream regulatory
      sequence and most of the first intron of the rat Col1a1 gene. The construct was
      expressed at the mRNA and protein level in transfected osteoblasts. Five lines of
      transgenic mice were generated by embryo microinjection. Transgene mRNA levels
      were highest in calvaria, long bone and tendon, and lower in skin. Serum IGF-I
      and body weight were increased in males and females only in the highest
      expressing line. Histomorphometry showed that transgenic calvaria were wider and
      had greater marrow area and bone area. Transgenic calvaria had increased
      osteoclast number per bone surface. Percent collagen synthesis and cell
      replication were increased in transgenic calvaria. Femur length, cortical width
      and cross-sectional area were increased in transgenic femurs of the highest
      expressing line, while femoral trabecular bone volume was little affected. Thus,
      broad overexpression of IGF-I in cells of the osteoblast lineage increased
      indices of bone formation and resorption.

PMID- 16644299
TI  - Pamidronate does not adversely affect bone intrinsic material properties in
      children with osteogenesis imperfecta.
AB  - Cyclical intravenous pamidronate therapy increases bone mass in children with
      osteogenesis imperfecta (OI), but the effect on the intrinsic material properties
      of bone is unknown at present. Thus, a possible influence of pamidronate
      treatment on bone quality at the material level might negate the beneficial
      effects of the gain in bone mass and lead to bone fragility in the long term. In
      the present study, we used transiliac bone biopsy samples and assessed the
      intrinsic material properties of the bone tissue at the micron-level by combined
      backscattered electron imaging and nanoindentation. Paired iliac bone samples
      from 14 patients (age 3 to 17 years) with severe OI before and after 2.5 +/- 0.5
      years (mean +/- SD) of pamidronate treatment as well as age-matched controls were
      examined. Bone histomorphometry was performed in all samples and confirmed an
      increase of bone mass in treated patients. Backscattered electron imaging was
      used to measure the weighted mean calcium content (Ca(Mean)), the most frequent
      calcium content (Ca(Peak)), the variation in mineralization (Ca(Width)) and the
      amount of lowly mineralized areas (Ca(Low)) that correspond to sites of primary
      mineralization. Nanoindentation was performed in a subgroup of 6 patients and 6
      controls to determine hardness and elastic modulus. Compared to controls,
      untreated OI patients had a significantly higher degree of bone matrix
      mineralization (Ca(Peak) +7%, P < 0.001) and a strong reduction of Ca(Low) (-38%,
      P < 0.001) despite enhanced bone formation, as well as increased hardness (+21%,
      P < 0.01) and elastic modulus (+13%, P < 0.01). However, none of these parameters
      was significantly altered by the subsequent pamidronate treatment. This shows
      that OI bone is stiffer and more mineralized and that, despite the enhanced bone
      formation rate in these patients, areas of primary mineralization are hardly
      visible. We also conclude that pamidronate treatment in children with OI does not
      have an adverse effect on the intrinsic material properties of bone and, as a
      consequence, that a long-term administration of the drug might not increase
      brittleness and fragility of the bone matrix. The antifracture effectiveness of
      pamidronate treatment in OI, as shown in previous clinical studies, has to be
      explained by the increase of mainly cortical bone volume.

PMID- 16644300
TI  - Homocysteine enhances apoptosis in human bone marrow stromal cells.
AB  - INTRODUCTION: High plasma homocysteine (Hcy) levels have been associated with
      increased risk of fracture. Since Hcy has been shown to induce apoptosis in many
      cell types, including vascular endothelial cells, we hypothesized that Hcy would
      have a similar apoptotic effect on osteoblasts, leading to osteoporosis by
      reducing bone formation. MATERIALS AND METHODS: Using primary human bone marrow
      stromal cells (hBMSC) and HS-5 cell line (human bone marrow stromal cell line),
      we investigated the effects of Hcy on these cells by cell viability assay and
      analysis of cytoplasmic histone-associated DNA fragments. Caspase activity assay,
      Western blots, and electrophoresis mobility shift assay (EMSA) were performed to
      find the mechanism of apoptosis. Intracellular reactive oxygen species (ROS) were
      measured by spectrometry using dichlorofluorescein diacetate, and cellular total
      glutathione level was determined by a commercially available kit. N
      acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) were used as tools
      for investigating the role of ROS and nuclear factor-kappaB (NF-kappaB),
      respectively. RESULTS: Hcy induced apoptosis in primary human bone marrow stromal
      cells and the HS-5 cell line, and this apoptotic effect was caspase-dependent. In
      addition, Hcy increased cytochrome c release into the cytosol, and activated
      caspase-9 and caspase-3, but not caspase-8, indicating that Hcy induces apoptosis
      via the mitochondria pathway. Hcy increased ROS, and NAC inhibited the apoptotic
      effect of Hcy. Western blot and EMSA showed that Hcy activated the NF-kappaB
      pathway. PDTC blocked Hcy-induced caspase-3 activation and apoptosis. CONCLUSION:
      These results suggest that Hcy induces apoptosis via the ROS-mediated
      mitochondrial pathway and NF-kappaB activation in hBMSCs, and that Hcy may
      contribute to the development of osteoporosis by reducing bone formation.
      Antioxidants may have a role in preventing bone loss in individuals with
      hyperhomocysteinemia.

PMID- 16644301
TI  - Elevated serum FGF23 concentrations in plasma cell dyscrasias.
AB  - Fibroblast growth factor 23 (FGF23) is now recognized as a key regulator of
      phosphate metabolism. Numerous reports have found elevated serum FGF23
      concentrations in oncogenic osteomalacia associated with mesenchymal tumors.
      Hypophosphatemic osteomalacia more rarely occurs in non-mesenchymal tumors. We
      identified elevated serum FGF23 levels in one patient with chronic lymphatic
      leukemia (CLL) and hypophosphatemia, prompting us to examine FGF23 concentrations
      in other patients with B-cell neoplasms. FGF23 levels were elevated in several
      patients with myeloma and monoclonal gammopathy of undetermined significance
      (MGUS), and were significantly associated with serum paraprotein and beta-2
      microglobulin concentrations in these patients. Hypophosphatemia was not observed
      even in those patients with elevated FGF23, and a weak positive correlation was
      noted between serum FGF23 and phosphate concentrations. Malignant plasma cells in
      bone marrow trephines from patients with myeloma showed cytoplasmic expression of
      FGF23, similar to the cytoplasmic localization of FGF23 already described in
      mesenchymal tumors associated with oncogenic osteomalacia. Our findings
      contribute to an expanding literature regarding abnormal FGF/FGF receptor
      signaling in myeloma. The absence of hypophosphatemia in these cases suggests
      either that FGF23 produced by clonal B-cells lacks systemic bioactivity or that
      other factors contribute to maintain serum phosphate. We suggest that the
      relationship between FGF23 and skeletal disease associated with plasma cell
      dyscrasias deserves further study.

PMID- 16644302
TI  - Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin)
      versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus
      Atorvastatin (VYVA) Study.

PMID- 16644303
TI  - The vulnerable endothelium: priming the vascular endothelium for thrombosis with
      unfractionated heparin: biologic plausibility for observations from the Superior
      Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein
      IIb/IIIa Inhibitors (SYNERGY) trial (Am J Heart 2005;150:189-92).

PMID- 16644304
TI  - Inflammatory response after intervention assessed by serial C-reactive protein
      measurements correlates with restenosis in patients treated with coronary
      stenting.

PMID- 16644306
TI  - The nonspecific anti-inflammatory therapy with methotrexate for patients with
      chronic heart failure.

PMID- 16644308
TI  - Schizophrenia and increased risk of cardiovascular disease.

PMID- 16644309
TI  - Coronary artery imaging with multidetector computed tomography: a call for an
      evidence-based, multidisciplinary approach.
AB  - Modern multidetector computed tomography systems are capable of a comprehensive
      assessment of the cardiovascular system, including noninvasive assessment of
      coronary anatomy. Multidetector computed tomography is expected to advance the
      role of noninvasive imaging for coronary artery disease, but clinical experience
      is still limited. Clinical guidelines are necessary to standardize scanner
      technology and appropriate clinical applications for coronary computed
      tomographic angiography. Further evaluation of this evolving technology will
      benefit from cooperation between different medical specialties, imaging
      scientists, and manufacturers of multidetector computed tomography systems,
      supporting multidisciplinary teams focused on the diagnosis and treatment of
      early and advanced stages of coronary artery disease. This cooperation will
      provide the necessary education, training, and guidelines for physicians and
      technologists assuring standard of care for their patients.

PMID- 16644310
TI  - Management of elderly patients with congestive heart failure--design of the Trial
      of Intensified versus standard Medical therapy in Elderly patients with
      Congestive Heart Failure (TIME-CHF).
AB  - BACKGROUND: Little is known about the management of elderly patients with
      congestive heart failure (CHF) although they represent the majority of the CHF
      population. Therefore, the TIME-CHF study was set up (1) to evaluate the medical
      management of very old patients (> or = 75 years) with CHF compared with younger
      patients (60-74 years), (2) to compare an intensified with a standard treatment
      approach, and (3) to differentiate between systolic and diastolic dysfunction
      (ejection fraction < or = 45% vs > 45%). METHODS: In a prospective single-blinded
      multicenter trial, 824 symptomatic patients, CHF hospitalization within the last
      year and elevated NT-BNP, are randomized to an intensified versus a standard
      medical therapy. Treatment strategies follow the published guidelines with the
      aim to reduce symptoms to NYHA class < or = II (standard) or, additionally, NT
      BNP levels below twice the upper limit of normal (intensified). The primary end
      points are 18-month hospitalization-free survival and quality of life. RESULTS:
      By the end of 2004, 297 patients have been included, 147 randomized to
      intensified and 150 to standard therapy. Mean age in the older age group was 82
      +/- 4 years (n = 174) and 69 +/- 4 years in the younger group (n = 123),
      respectively. Ejection fraction was > 45% in 26% and 10%, respectively.
      Significant comorbidities were present in 93% of patients. CONCLUSION: TIME-CHF
      will be the first prospective randomized trial to comprehensively study the
      management of elderly patients with CHF. It will provide unique information
      comparing two treatment strategies in two age groups irrespective of ejection
      fraction regarding prognosis, quality of life, as well as resource utilization
      and costs.

PMID- 16644311
TI  - The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in
      Patients with Atrial Fibrillation) trial.

PMID- 16644312
TI  - 24-hour ambulatory blood pressure monitoring.

PMID- 16644313
TI  - Missed opportunities in the secondary prevention of myocardial infarction: an
      assessment of the effects of statin underprescribing on mortality.
AB  - BACKGROUND: The benefits of statins for the secondary prevention of coronary
      heart disease are well established. Previous research indicates that patients at
      the greatest risk of cardiovascular events are the least likely to receive
      statins. We explored the potential reduction in mortality at the population level
      that could result from improving statin prescribing among patients least likely
      to be prescribed a statin after acute myocardial infarction (AMI). METHODS:
      Simulation analysis of detailed clinical data for a population-based sample of
      7285 AMI survivors discharged from 102 hospitals between April 1, 1999, and March
      31, 2001 in Ontario, Canada, was done. Using estimates obtained from randomized
      controlled trials, we estimated the reduction in 3-year all-cause mortality
      associated with improved statin prescribing at hospital discharge. RESULTS:
      Overall, 35.6% of patients received a statin prescription at hospital discharge.
      We estimate that increasing statin prescribing among patients least likely to
      receive them (ie, the lowest quintile of propensity to receive a prescription at
      discharge) from the current rate of 7.8% to the rate among all patients (35.6%)
      could decrease AMI mortality by 83 deaths in Ontario per year (2.1% of all post
      AMI deaths within 3 years of discharge). Increasing statin prescribing to 70%
      among all patients with AMI could avert 312 deaths per year in Ontario. Factoring
      in low rates of adherence to statin therapy would reduce these estimates to 33
      and 126, respectively. CONCLUSIONS: Modest increases in statin prescribing for
      patients least likely to receive one could decrease post-AMI mortality at the
      population level.

PMID- 16644314
TI  - Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target
      levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using
      Rosuvastatin therapY (MERCURY) II.
AB  - BACKGROUND: National Cholesterol Education Program Adult Treatment Panel III
      guidelines for patients at a high risk of coronary heart disease set a low
      density lipoprotein cholesterol (LDL-C) target of < 100 mg/dL. This target can be
      difficult to attain with diet and current therapy. METHODS: In a 16-week
      multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20
      mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40
      mg for 8 weeks. Patients either remained on starting treatment or switched to
      lower or milligram-equivalent doses of rosuvastatin for 8 more weeks. RESULTS: At
      16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin
      10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20
      mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients
      to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001)
      or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients
      achieved an LDL-C target of < 70 mg/dL when changed to rosuvastatin from
      atorvastatin or simvastatin (within-arm comparisons P < .01). More
      hypertriglyceridemic patients (triglycerides > or = 200 mg/dL) met LDL-C, non
      high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by
      changing to rosuvastatin. Switching to rosuvastatin produced greater reductions
      in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All
      treatments were well tolerated, with no differences among treatment groups in
      skeletal muscle, hepatic, or renal toxicity. CONCLUSION: Rosuvastatin 10 or 20 mg
      is an effective and safe therapeutic option for high-risk patients to achieve
      their lipid and apolipoprotein targets.

PMID- 16644315
TI  - Statins are associated with lower risk of gastrointestinal bleeding in patients
      with unstable coronary syndromes: analysis of the Orbofiban in Patients with
      Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI
      16) trial.
AB  - BACKGROUND: It has recently been shown that statins increase the myocardial
      content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of
      PG production may protect the gastric mucosa and prevent gastrointestinal (GI)
      bleeding. We hypothesized that statins would lower the risk of GI bleeding
      associated with antiplatelet therapy in patients with acute coronary syndromes
      (ACS). METHODS: We retrospectively analyzed data on 10288 patients with ACS
      included in the OPUS-TIMI 16 trial and received aspirin and either the oral
      IIb/IIIa inhibitor orbofiban or placebo. RESULTS: Inhospital GI bleeding rate was
      significantly lower in patients who were receiving lipid-lowering drugs before
      admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout
      10 months of follow-up, GI bleeding occurred in 1.8% of non-statin users compared
      with 1.0% of statin users (P = .001). Statin use was associated with less overall
      bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups
      (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with
      statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P =
      .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression
      analysis showed that age > 65 years, orbofiban treatment, Killip class > 1,
      history of cerebrovascular disease, and calcium-channel blocker use were
      associated with higher risk of GI bleeding, whereas statin therapy was associated
      with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). CONCLUSIONS:
      Statins may exert protective effect against GI bleeding in patients with ACS.
      Additional studies are warranted to explore this additional potential benefit of
      statins.

PMID- 16644316
TI  - Lack of effect of enteric coating on aspirin-induced inhibition of platelet
      aggregation in healthy volunteers.
AB  - BACKGROUND: Aspirin inhibits platelet aggregation and is widely used in the
      treatment of cardiovascular disease. Some individuals are less responsive to
      aspirin's antiplatelet effect, a phenomenon termed aspirin resistance. It is not
      known whether the antiplatelet effect is fully preserved with the enteric-coated
      (EC) formulation. METHODS: We performed a prospective randomized trial of 50
      healthy volunteers using a crossover design to compare the EC with the standard
      aspirin formulations. The subjects received a 7-day course of each aspirin
      formulation (81-mg) (Bayer Corporation, Morristown, NJ) separated by a 3-week
      washout period. Platelet function was measured before and after each course using
      optical aggregometry (with arachidonic acid and adenosine diphosphate as
      agonists) and a point-of-care platelet assay. RESULTS: The assays were
      reproducible, and the variation in baseline platelet function was small to
      moderate between the subjects. There was no difference in the extent of platelet
      inhibition between the EC and standard formulations with any of the 3 assays.
      With the point-of-care platelet assay, the mean aspirin effect favoring the
      standard formulation (more aggregation inhibition) compared with the EC
      formulation was 1.6% +/- 15.8% (P = .60 for difference between the formulations).
      The corresponding optical aggregometry values were -3.4% +/- 39.5% (P = .97) and 
      1.4% +/- 16.6% (P = .75) for arachidonic acid and adenosine diphosphate,
      respectively. CONCLUSIONS: Compared with standard aspirin, EC aspirin appears to
      exhibit similar inhibition of platelet aggregation in healthy volunteers.
      Furthermore, point-of-care platelet assessment correlated well with the gold
      standard of laboratory-based optical platelet aggregometry.

PMID- 16644317
TI  - Periodontal infections cause changes in traditional and novel cardiovascular risk
      factors: results from a randomized controlled clinical trial.
AB  - BACKGROUND: Chronic infections, such as periodontitis, are associated with
      increased risk of systemic diseases driven by a persistent low-grade systemic
      inflammation and metabolic changes. Severity of periodontitis has also been
      associated with increased systolic blood pressure (BP). However, the issue
      remains poorly investigated. We aimed to estimate the effect of periodontal
      therapy on traditional and novel cardiovascular risk factors in systemically
      healthy individuals who have periodontitis. METHODS: We enrolled 40 otherwise
      healthy patients with severe chronic generalized periodontitis in a 6-month pilot
      intervention trial. Individuals were randomized either to a standard course of
      periodontal therapy (subgingival scaling and root planing) or an intensive one
      (including the adjunctive use of a locally delivered antimicrobial, IPT).
      RESULTS: Compared to control, IPT produced significant reductions in a cluster of
      inflammatory markers at 1 (P = .0406) and 2 (P = .0060) months together with an
      improvement in lipid markers at 2 (P = .0320) and 6 (P = .0432) months after
      therapy. Intensive periodontal therapy produced greater reductions in IL-6 at 1
      (0.4 +/- 0.2 ng/L difference, 95% CI 0.03-0.9, P = .0284) and 2 months (0.3 +/-
      0.2 ng/L difference, 95% CI 0.1-0.8, P = .0284), together with decreases in C
      reactive protein (0.4 +/- 0.2 mg/L difference, 95% CI 0.01-0.8, P = .0438) and
      total cholesterol (0.3 +/- 0.1 mmol/L difference, 95% CI 0.04-0.6, P = .0254).
      Moreover, a 7 +/- 3-mm Hg decrease in systolic BP was observed at 2 months in the
      IPT group (95% CI 1-12, P = .0211), and this difference was greater in current
      smokers (14 +/- 5 mm Hg 95% CI 3-25, P = 0.0124). Intensive periodontal therapy
      subjects exhibited a 1.53% +/- 1.20% (95% CI 1.05-2.24, P = .0290) and 2.00% +/-
      1.42% (95% CI 0.98-4.09, P = .0568) decreases in cardiovascular risk scores
      (Framingham) at 2 and 6 months, respectively, when compared to those in the
      standard group. CONCLUSIONS: Our findings suggest that intensive periodontal
      treatment reduces systemic inflammatory markers and systolic BP, and improves
      lipid profiles with subsequent changes in cardiovascular risk when compared to
      standard therapy.

PMID- 16644318
TI  - Prevention of atrial fibrillation in patients with symptomatic chronic heart
      failure by candesartan in the Candesartan in Heart failure: assessment of
      Reduction in Mortality and morbidity (CHARM) program.
AB  - BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart
      failure (CHF). Experimental and small patient studies have demonstrated that
      blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM
      program, the effects of the angiotensin receptor blocker candesartan on
      cardiovascular mortality and morbidity were evaluated in a broad spectrum of
      patients with symptomatic CHF. CHARM provided the opportunity to prospectively
      determine the effect of candesartan on the incidence of new AF in this CHF
      population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved
      left ventricular systolic function were randomized to candesartan (target dose 32
      mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM.
      The major outcomes were cardiovascular death or CHF hospitalization and all-cause
      mortality. The incidence of new AF was a prespecified secondary outcome. Median
      follow-up was 37.7 months. A conditional logistic regression model for stratified
      data was used. RESULTS: 6446 patients (84.8%) did not have AF on their baseline
      electrocardiogram. Of these, 392 (6.08%) developed AF during follow-up, 177
      (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio
      0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates,
      the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no
      heterogeneity of the effects of candesartan in preventing AF between the 3
      component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor
      blocker candesartan reduced the incidence of AF in a large, broadly-based,
      population of patients with symptomatic CHF.

PMID- 16644319
TI  - Relationship of dose of background angiotensin-converting enzyme inhibitor to the
      benefits of candesartan in the Candesartan in Heart failure: Assessment of
      Reduction in Mortality and morbidity (CHARM)-Added trial.
AB  - BACKGROUND: Whether an angiotensin receptor blocker is of benefit when added to a
      full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF)
      is uncertain. METHODS: The effect of candesartan, compared with placebo, in 2548
      patients randomized in the CHARM-Added trial was analyzed according to (i) ACE
      inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii)
      combination treatment with ACE inhibitor and beta-blocker at baseline. The main
      outcome was the composite of cardiovascular death or HF hospitalization. RESULTS:
      The benefit of candesartan was not modified by the dose of ACE inhibitor. In all
      patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary
      outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended
      dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95;
      interaction P value .26). In patients taking a Food and Drug Administration
      designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57
      0.98; interaction P value .29). The benefit of candesartan was preserved in
      patients taking beta-blockers in addition to a higher dose of ACE inhibitor and
      in patients maintaining a high dose of ACE inhibitor throughout follow-up.
      CONCLUSIONS: These clinical findings support the pharmacologic evidence that ACE
      inhibitors and angiotensin receptor blockers have distinct mechanisms of action
      and show that their combined use improves outcomes in patients with HF more than
      an evidence-based dose of ACE inhibitor alone.

PMID- 16644320
TI  - Multifaceted intervention to promote beta-blocker use in heart failure.
AB  - BACKGROUND: Despite a survival benefit and guideline recommendation for beta
      blockers in left ventricular systolic dysfunction, beta-blockers are underused in
      clinical practice. METHODS: Medical practices with > or = 15 patients with heart
      failure (HF) in the Duke Databank for Cardiovascular Disease (DDCD) were
      identified for a prospective, randomized study using a multifaceted intervention
      to improve beta-blocker use. Intervention practices received provider education,
      patient education materials, feedback on beta-blocker use of their patients with
      HF, and access to telephone consultation with an HF expert. The primary outcome
      was a comparison between intervention and control practices of the proportion of
      patients with HF self-reporting beta-blocker use on their first routine DDCD
      follow-up in the postintervention year. A random effects model was used for the
      analysis. RESULTS: Post intervention, 2631 patients (1701 in 23 intervention
      practices and 930 in 22 control practices) completed DDCD follow-up. No
      significant difference in the proportion of patients with HF reporting beta
      blocker use was found in the intervention versus control groups (OR 1.16, 95% CI
      0.94-1.43, P = .2), although more patients in the intervention group started a
      beta-blocker than stopped a beta-blocker during the study period (P = .02).
      CONCLUSIONS: This multifaceted intervention did not significantly increase the
      mean proportion of patients taking beta-blockers within practices exposed to the
      intervention, although favorable trends were observed. Further studies are needed
      to identify and evaluate strategies for translating evidence into clinical
      practice to reduce the global health burden associated with HF.

PMID- 16644321
TI  - How obesity affects the cut-points for B-type natriuretic peptide in the
      diagnosis of acute heart failure. Results from the Breathing Not Properly
      Multinational Study.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is valuable in diagnosing heart
      failure (HF), but its utility in obese patients is unknown. Studies have
      suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however,
      there is an inverse relation between BNP levels and body mass index. We evaluated
      differential cut-points for BNP in diagnosing acute HF across body mass index
      levels to determine whether alternative cut-points can improve diagnosis.
      METHODS: The Breathing Not Properly Multinational Study was a 7-center,
      prospective study of 1586 patients who presented to the Emergency Department with
      acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and
      weight data were available for 1368 participants. The clinical diagnosis of HF
      was adjudicated by 2 independent cardiologists who were blinded to BNP results.
      RESULTS: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL)
      in lean, overweight/obese, and severely/morbidly obese patients were 643, 462,
      and 247 for patients with acute HF, and 52, 35, and 25 in those without HF,
      respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic
      peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL
      for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in
      severely/morbidly obese patients. CONCLUSIONS: Body mass index influences the
      selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP >
      or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity.
      A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to
      increase specificity.

PMID- 16644322
TI  - Gray zone BNP levels in heart failure patients in the emergency department:
      results from the Rapid Emergency Department Heart Failure Outpatient Trial
      (REDHOT) multicenter study.
AB  - OBJECTIVES: The study purpose was to examine "gray zone" B-type natriuretic
      peptide (BNP) levels (100-500 pg/mL) in terms of associated clinical factors,
      perceived severity, and outcomes in patients with established congestive heart
      failure (CHF). BACKGROUND: Although gray zone BNP levels may have diagnostic
      ambiguity, the implications of these levels in patients with an established
      diagnosis of CHF have not been examined. METHODS: REDHOT was a national
      prospective study in which 464 patients seen in the emergency department with
      dyspnea had BNP levels drawn. Entrance criteria included a BNP > 100 pg/mL;
      however, physicians were blinded to the actual BNP level. Patients were followed
      up for 90 days. RESULTS: Thirty-three percent had gray zone BNP levels. There was
      no difference in perceived New York Heart Association class (P = .32) or
      admission rates (P = .76) between the gray zone and non-gray zone groups; 62% of
      patients with a gray zone BNP were identified as class III or IV CHF. Despite
      this perceived severity, the 90-day event rate was lower in the gray zone group
      (19.2% vs 32.9%, respectively, P = .002). Although patients in the gray zone had
      more symptoms of concomitant pulmonary disease, multivariate analysis could not
      demonstrate any variable that worsened the prognosis of patients with a gray zone
      BNP level. CONCLUSIONS: In patients with established CHF, those with gray zone
      BNP levels have a better prognosis than those with non-gray zone levels despite
      being perceived by physicians as having New York Heart Association class III or
      IV CHF.

PMID- 16644323
TI  - Low prevalence of B-type natriuretic peptide levels < 100 pg/mL in patients with
      heart failure at hospital discharge.
AB  - BACKGROUND: In patients with acute heart failure (HF) presenting at the emergency
      department, a B-type natriuretic peptide (BNP) level < 100 pg/mL was found in
      only 10% of the patients. However, in a more stable outpatient HF population from
      another study, a BNP level < 100 pg/mL was found in as many as 21% of the
      patients. Therefore, we aimed to investigate the prevalence and characteristics
      of stabilized patients with BNP levels < 100 pg/mL before discharge after
      admission for decompensated heart failure HF. METHODS: We investigated 601
      patients with HF who were part of a large-scale multicenter study in The
      Netherlands. All patients had been admitted for decompensated HF, and their BNP
      levels were measured before discharge when they had been clinically stabilized.
      Clinical characteristics of patients with BNP levels < 100 and > or = 100 pg/mL
      were compared. RESULTS: Patients were 70 +/- 12 years old, 61% were men, and mean
      left ventricular ejection fraction was 0.34 +/- 0.14. Of these patients, 10% had
      BNP levels < 100 pg/mL. Patients with a BNP level < 100 pg/mL were similar in age
      and sex but had higher left ventricular ejection fraction (0.41 +/- 0.14 vs 0.33
      +/- 0.13, P < .001), body mass index, and hemoglobin and hematocrit
      concentrations compared with those with BNP levels > or = 100 pg/mL. CONCLUSIONS:
      In clinically stable patients with a recent admission for decompensated HF, only
      10% had BNP levels > or = 100 pg/mL. These patients with low BNP levels seemed to
      have less severe HF and more frequently had preserved systolic function compared
      with patients with BNP levels > or = 100 pg/mL.

PMID- 16644324
TI  - Intrafamilial variability of noncompaction of the ventricular myocardium.
AB  - BACKGROUND: Noncompaction of the ventricular myocardium (NVM) is a relatively
      uncommon form of cardiomyopathy characterized by a highly trabeculated
      myocardium. This report describes the clinical and genetic evaluation of a 3
      generation kindred. METHODS: Family members were initially evaluated by 2
      dimensional echocardiography. Most family members with signs of NVM were further
      evaluated by magnetic resonance imaging. Genetic analyses included mutational
      screening of the taffazin (TAZ) and alpha-dystrobrevin (DTNA) genes. RESULTS:
      Eight family members had signs of NVM. Considerable interindividual variation was
      noted in terms of spatial distribution and severity of affected regions and
      ventricular dysfunction. Depending on which of 2 previously proposed quantitative
      diagnostic criteria were used and where ventricular myocardial measurements were
      taken, between 4 and 7 of these individuals had findings that were considered
      diagnostic. Magnetic resonance imaging served as a useful adjunct for confirming
      or establishing diagnoses in all 8 individuals. No mutation was found in TAZ or
      DTNA. CONCLUSIONS: This kindred demonstrates the remarkably wide phenotypic
      spectrum that can be seen in familial cases of NVM, ranging from
      prenatal/neonatal lethality to a complete lack of symptoms. The fact that all 8
      affected individuals either have shown improvement in ventricular function or
      symptoms during childhood or have been asymptomatic indicates that NVM can have a
      relatively benign course. The degree and nature of cardiac involvement are also
      quite varied, and there is a weak correlation with ventricular function and
      symptoms. Evaluation of families with NVM requires careful assessment that uses a
      combination of imaging techniques and diagnostic criteria.

PMID- 16644325
TI  - Hospital cost effect of a heart failure disease management program: the
      Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) trial.
AB  - BACKGROUND: Determine the effect on hospitalization cost of a heart failure
      disease management (HFDM) program delivered within a diverse provider network as
      demonstrated in the SPAN-CHF randomized controlled trial. METHODS: The SPAN-CHF
      trial was a prospective randomized assessment of the effectiveness of HFDM
      delivered for 90 days across a diverse provider network in a heterogeneous
      population of 200 patients. Baseline clinical and demographic data were obtained
      on each patient, mortality was monitored, and hospitalizations were tracked for
      90 days. Cost estimates for each hospitalization were based on a subsample of
      patients seen at Tufts-New England Medical Center for whom hospitalization costs
      were calculated. Heart failure disease management program costs were estimated
      using a programmatic budget model. Hospital utilization and cost data were
      combined to estimate medical costs for intervention and control groups. RESULTS:
      Heart failure disease management had a favorable effect on heart failure
      hospitalization, which was partially offset by noncardiac hospitalizations. The
      relative odds of at least one all-cause hospitalization during the intervention
      period trended less for the intervention group compared with the control group
      (0.76 [95% CI 0.38-1.51]). The point estimate of the differential hospitalization
      cost between control and intervention groups was a reduction in cost of $375 per
      patient. The net effect including the costs of the program was an increase of
      $488 per patient for the intervention group compared with the control group. The
      program would have been cost saving if HFDM costs had been 24% lower. CONCLUSION:
      The HFDM intervention, administered over 90 days to patients hospitalized for
      heart failure, succeeded in reducing the rate of heart failure hospitalizations,
      although this effect was partially offset by an increase in non-heart failure
      hospitalizations. The resulting modest reduction in all-cause hospitalization
      costs was exceeded by the cost of the intervention. Thus, although the reduction
      in heart failure may be interpreted as an improvement in health status, it could
      not be considered cost saving.

PMID- 16644326
TI  - Sirolimus-eluting coronary stents in small vessels.
AB  - BACKGROUND: This prospective multicenter study compared angiographic in-lesion
      late lumen loss in de novo native coronary artery lesions (vessel diameter range
      2.25-2.75 mm, length range > or = 15 to < or = 30 mm) 8 months after the
      implantation of a sirolimus-eluting stent with that of similar vessels with the
      same drug-eluting stent or a bare stent of the SIRIUS study (historical
      controls). METHODS AND RESULTS: One hundred one patients (study group) were
      matched and compared with 323 patients receiving the bare stent (bare control
      group) and with 350 receiving the Cypher stent (Cypher control group) in the
      SIRIUS trial. Mean in-lesion late loss in the study group was lower than that in
      the bare control group (0.20 versus 0.76 mm, P < .0001) and not inferior to that
      in the Cypher control group (0.27 mm, P = .3). Adverse event rates (death and
      myocardial infarction) were similar between groups. At 8 months, target lesion
      revascularization rates were 0% in the study group, 13.2% in the bare control
      group (P < .001), and 4.6% in the Cypher control group (P = .03). CONCLUSIONS:
      The Cypher Bx Velocity stent was confirmed to be superior to the bare Bx Velocity
      stent in small coronary vessels in terms of in-lesion late loss 8 months after
      implantation.

PMID- 16644327
TI  - Coronary plaque composition of nonculprit lesions, assessed by in vivo
      intracoronary ultrasound radio frequency data analysis, is related to clinical
      presentation.
AB  - BACKGROUND: Identification of subclinical high-risk plaques is potentially
      important because they may have greater likelihood of rupture and subsequent
      thrombosis. The purpose of this study was to assess the relationship between
      plaque composition determined by intravascular ultrasound (IVUS) radio frequency
      (RF) data analysis and clinical presentation. METHODS: In 55 patients, a
      nonculprit vessel with < 50% diameter stenosis was studied with IVUS. Tissue maps
      were reconstructed from RF data using IVUS-Virtual Histology software. RESULTS:
      Mean percentage of the different plaque components were 0.99% +/- 0.9%, calcium;
      68.04% +/- 9.8%, fibrous; 19.31% +/- 7.3%, fibrolipidic; and 9.43% +/- 6.6%,
      lipid core. Mean lipid core percentage was significantly larger in patients with
      acute coronary syndrome (ACS) when compared with stable patients (12.26% +/- 7.0%
      vs 7.40% +/- 5.5%, P = .006). In addition, stable patients showed more fibrotic
      vessels (70.97% +/- 9.3% vs 63.96% +/- 9.1%, P = .007). There was no significant
      difference for either mean calcium (1.20% +/- 1.1% vs 0.83% +/- 0.7%, P = .124)
      or fibrolipidic (20.57% +/- 6.9% vs 18.40% +/- 7.6%, P = .281) percentages in ACS
      and stable patients, respectively. Vessel area obstruction did not differ between
      groups (46.49% +/- 10.9% vs 42.83% +/- 11.8%, P = .221). There was a significant,
      albeit weak, positive correlation between lipid core percentage and stenosis
      severity as determined by vessel area obstruction (r = 0.34, P = .015).
      CONCLUSIONS: In this study, plaque characterization of nonculprit vessels using
      spectral analysis of IVUS RF data analysis was significantly related to clinical
      presentation. Percentage of lipid core, a feature related to acute coronary
      events and worse prognosis, was significantly larger in patients with ACS.
      Conversely, stable patients showed more fibrotic content.

PMID- 16644328
TI  - In vivo relationship between compositional and mechanical imaging of coronary
      arteries. Insights from intravascular ultrasound radiofrequency data analysis.
AB  - OBJECTIVE: We sought to explore in vivo the relation between mechanical and
      compositional properties of matched cross sections (CSs) using novel catheter
      based techniques. BACKGROUND: Intravascular ultrasound (IVUS) palpography allows
      the assessment of local mechanical tissue properties. Spectral analysis of IVUS
      radiofrequency data (IVUS-VH) is a tool to assess plaque morphology and
      composition. METHODS AND RESULTS: Palpography analysis defined high- and low
      strain regions. One hundred twenty-three CSs (27 vessels) were colocalized. The
      mean strain value was higher in CSs with necrotic core (NC) in contact with the
      lumen than in CSs with no NC contact with the lumen (1.03 +/- 0.5 vs 0.86 +/-
      0.4, P = .06). Mean relative calcium (1.61 +/- 2.5% vs 0.25 +/- 0.7%, P = .001)
      and NC (15.64 +/- 10.6% vs 2.8 +/- 3.9%, P < .001) content were significantly
      higher in the CSs with NC in contact with the lumen, whereas the inverse was seen
      for the fibrotic component of the plaque (64.16 +/- 11.6% vs 75.75 +/- 13.7, P <
      .001). The sensitivity, specificity, positive predictive value, and negative
      predictive value of IVUS-VH to detect high strain were 75.0%, 44.4%, 56.3%, and
      65.1%, respectively. A significant inverse relationship was present between
      calcium and strain levels (r = -0.20, P = .03). After adjusting for univariate
      predictors, the contact of NC with the lumen was identified as the only
      independent predictor of high strain (OR 5.0, 95% CI 1.7-14.1, P = .003).
      CONCLUSION: In the present study, IVUS-VH showed an acceptable sensitivity to
      detect high strain. In turn, the specificity was low. Of interest, a significant
      inverse relationship was present between calcium and strain levels.

PMID- 16644329
TI  - Influence of sex on in-hospital outcomes and long-term survival after
      contemporary percutaneous coronary intervention.
AB  - BACKGROUND: Early studies suggested that morbidity and mortality after
      percutaneous coronary intervention (PCI) were greater for women than men.
      However, in recent reports, sex-related differences in short-term outcome have
      decreased as outcomes among women have improved. OBJECTIVE: The aim of the study
      was to evaluate the effect of sex on long-term mortality among a large cohort of
      patients undergoing PCI in the contemporary era. METHODS: Three hospitals in New
      York City contributed prospectively defined data elements on 4284 consecutive
      patients undergoing PCI in 1998 to 1999. All-cause mortality at a mean follow-up
      of 3 years was the primary end point. RESULTS: Of the 4284 patients, 1331 (31%)
      were women. Women were significantly older than men (mean age 67 vs 62 years, P <
      .001) and less often white (72% vs 80%, P < .001). Hypertension (78% vs 66%, P <
      .001) and diabetes (36% vs 22%, P < .001) were more prevalent in women. Prior
      cardiac surgery (14% vs 19%, P = .001) and previous myocardial infarction (MI)
      (33% vs 36%, P = .08) were less common among women. Presentation with unstable
      angina was more frequent in women (45% vs 41%, P = .034), whereas presentation
      with acute MI did not differ by sex. Congestive heart failure developed more
      commonly among women (7.1% vs 4.1%, P < .001). The extent of coronary disease (1
      , 2-, or 3-vessel disease) did not differ between women and men. Mean ejection
      fraction was 52% in women and 50% in men (P < .001). Stents were placed in 77% of
      both groups. Procedural success was 97% for both women and men. Inhospital
      adverse outcomes including death, post-PCI MI, emergency bypass surgery, abrupt
      closure, and stent thrombosis were uncommon and not different between groups.
      Mortality at 3 years was 10% for women and 8.9% for men (P = .197). However,
      using Cox proportional hazards analysis to adjust for comorbidities and possible
      confounders, female sex was associated with a significant independent reduction
      in the hazard of long-term mortality (hazard ratio 0.78, 95% CI 0.620-0.969, P =
      .02). CONCLUSIONS: Despite more high-risk characteristics, female sex conferred a
      long-term survival advantage after PCI.

PMID- 16644330
TI  - Preprocedural statin use is associated with a reduced hazard of postprocedural
      myonecrosis in patients undergoing rotational atherectomy--a propensity-adjusted
      analysis.
AB  - Incidence of myonecrosis in patients undergoing rotational atherectomy was
      evaluated by preprocedural statin use. The incidence of any myonecrosis (24.1% vs
      52.3%, P < .001) or significant myonecrosis (7.5% vs 21.8%, P < .001) was
      significantly lower among patients pretreated with statins. This difference
      remained significant after multivariable and propensity adjustment.

PMID- 16644331
TI  - Ischemic and bleeding outcomes in women treated with bivalirudin during
      percutaneous coronary intervention: a subgroup analysis of the Randomized
      Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.
AB  - BACKGROUND: Outcomes in women undergoing percutaneous coronary intervention (PCI)
      in the contemporary era are poorly defined. The REPLACE-2 trial demonstrated that
      bivalirudin with provisional glycoprotein IIb/IIIa (GpIIb-IIIa) blockade is
      noninferior to heparin with planned GpIIb-IIIa blockade during PCI, with regard
      to ischemic and bleeding end points. OBJECTIVES: The aim of this study was to
      define sex-based clinical ischemic and bleeding outcomes from the REPLACE-2
      trial. METHODS: A retrospective sex-based subgroup analysis of the REPLACE-2
      trial comparing clinical ischemic and inhospital bleeding end points was
      conducted. RESULTS: Compared with men in REPLACE-2, women were older, had more
      diabetes, congestive heart failure and hypertension, and less prior
      revascularization and myocardial infarction. Female sex was a univariate
      predictor of death and bleeding complications. Among women treated with either
      bivalirudin or heparin, there was no significant difference in the individual or
      composite ischemic end points of death, myocardial infarction, or urgent
      revascularization at 30 days or 6 months. Protocol-defined major bleeding, minor
      bleeding, and access site bleeding were less frequent with bivalirudin compared
      with heparin. Multivariable modeling found no significant interactions between
      sexes, with the composite ischemic end point, major bleeding, or 1-year
      mortality. CONCLUSIONS: Women remain at higher risk for poorer outcomes with
      contemporary PCI, likely because of comorbidities. Bivalirudin with provisional
      GpIIb-IIIa confers similar protection against ischemic end points compared with
      heparin and planned GpIIb-IIIa blockade and significantly reduces the inherent
      bleeding risk of women undergoing contemporary PCI.

PMID- 16644332
TI  - Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine for the
      prevention of contrast nephropathy in diabetics.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of
      contrast-associated nephropathy irrespective of their baseline creatinine (Cr).
      We tested the efficacy of N-acetylcysteine (NAC) relative to hydration in
      unselected patients (irrespective of baseline Cr) with DM. METHODS: We conducted
      a randomized open-label study comparing hydration alone (combined oral and rapid
      intravenous hydration, n = 69) to NAC plus hydration (similar hydration protocol
      plus NAC 600 mg BID x 4 doses, n = 68) in diabetic patients (mean age 65 +/- 10
      years, 65% men) undergoing elective coronary angiography. The primary end point
      was the mean change in serum Cr measured up to 96 hours postangiography. RESULTS:
      Baseline Cr was 1.14 +/- 0.43 mg/dL (Cr > or = 1.3 mg/dL in 37 subjects).
      Baseline characteristics including blood urea nitrogen, Cr, and contrast volume
      were similar between the 2 groups. The mean Cr change in the NAC group was 0.14
      +/- 0.47 versus 0.08 +/- 0.11 mg/dL in the hydration only group (P = NS).
      Contrast-associated nephropathy, defined as a > or = 0.5 mg/dL increase in Cr,
      was significantly more common in the NAC group, 9.2% versus 1.4%, P = .043.
      Similar results were found in the subgroup of participants with either an
      increased baseline serum Cr (> or = 1.3 mg/dL) or in those receiving high
      contrast volumes (> 100 mL). CONCLUSIONS: N-Acetylcysteine provides no benefit
      over an aggressive hydration protocol in patients with DM undergoing coronary
      angiography.

PMID- 16644333
TI  - Effects of a statewide physician-led quality-improvement program on the quality
      of cardiac care.
AB  - BACKGROUND: Several states have implemented mandatory public reporting of
      outcomes of cardiac revascularization procedures. Washington is the first to
      develop a nonmandatory, physician-led reporting program with public
      accountability and universal hospital participation. The purpose of this study
      was to determine whether quality improvement interventions resulted in the
      correction of data deficiencies and performance outliers for cardiac
      revascularization procedures. METHODS: From 1999 through 2003, there were 18
      hospitals with coronary bypass surgery and interventional cardiology programs and
      12 with only the latter. All patients > or =18 years undergoing 24372 isolated
      coronary bypass surgeries and 59,656 percutaneous coronary interventions were
      included. After 1999 to 2001 data were analyzed in early 2002, the Clinical
      Outcomes Assessment Program implemented a 6-step quality-improvement intervention
      to measure and remeasure data quality, process compliance, and performance.
      RESULTS: In 2003, 4 of the 18 surgery programs had 1 statistical outlier with
      respect to 4 performance measures, whereas 2 of 30 coronary intervention programs
      were mortality outliers. For bypass surgery, all programs maintained full
      compliance with program standards by adhering to timely and reliable submission
      of data, developing plans to address performance outliers, and demonstrating that
      outlier status did not persist from baseline to remeasurement. For coronary
      interventions, 1 program was a persistent outlier for mortality in 2002 and 2003.
      CONCLUSIONS: The Clinical Outcomes Assessment Program has successfully monitored
      cardiac care patterns in Washington State over a 5-year period. Most hospitals
      that perform coronary revascularization procedures meet acceptable performance
      standards.

PMID- 16644334
TI  - Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation.
      Maintenance of sinus rhythm after conversion to sinus rhythm.
AB  - BACKGROUND: Azimilide dihydrochloride (azimilide) is an investigational
      antiarrhythmic drug that has been tested in patients with a variety of
      arrhythmias. In patients with atrial fibrillation, it has shown excellent
      efficacy in some previous trials and minimal efficacy in others. METHODS:
      Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months
      were eligible for this multicenter, randomized, placebo-controlled clinical
      trial. Patients were admitted to a hospital and randomly assigned to receive
      either azimilide 125 mg or a matched placebo twice daily for 3 days and then once
      daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm
      restored by electric cardioversion on day 4 were discharged from the hospital.
      Recurrence of atrial fibrillation was documented by electrocardiogram. In the
      primary efficacy analysis, time to recurrence in the 2 treatment groups was
      compared with the log-rank test in the subgroup of patients with structural heart
      disease. Safety was assessed as deaths, adverse events, and serious adverse
      events. RESULTS: A total of 446 patients were randomized in the study; 314 were
      in the subgroup with structural heart disease. The median time to arrhythmia
      recurrence in both treatment groups with structural heart disease was 13 days,
      and the difference between treatments was not significant (P = .4596, n = 314).
      The relative risk for recurrence (placebo:azimilide) was 1.104 (95% CI 0.849
      1.436). There was 1 death in the placebo group and 3 in the azimilide group.
      CONCLUSIONS: Azimilide did not demonstrate clinically important or statistically
      significant efficacy in reducing the risk for arrhythmia recurrence in patients
      with structural heart disease who were in atrial fibrillation and converted to
      sinus rhythm.

PMID- 16644335
TI  - Randomized comparison of simultaneous biventricular stimulation versus optimized
      interventricular delay in cardiac resynchronization therapy. The
      Resynchronization for the HemodYnamic Treatment for Heart Failure Management II
      implantable cardioverter defibrillator (RHYTHM II ICD) study.
AB  - BACKGROUND: The clinical value of interventricular (V-V) delay optimization in
      patients with chronic congestive heart failure (CHF) undergoing implantation of a
      device for cardiac resynchronization therapy (CRT) has not been clearly
      demonstrated. METHODS: RHYTHM II was a single-blind randomized trial including
      121 recipients of a device for CRT with cardioverter/defibrillator capabilities
      (CRT-D) randomly assigned in a 1:3 ratio to simultaneous (n = 30) versus
      optimized (OPT) (n = 91) biventricular pacing. V-V delay was optimized by
      echocardiography. The study end points were (1) freedom from CRT-D system-related
      complications and (2) changes between preimplant and 6 months of follow-up in (a)
      New York Heart Association CHF functional class, (b) distance covered during a 6
      minute hall walk, and (c) quality of life (QOL). RESULTS: In the OPT group, the V
      V delay ranged from 0 to 80 milliseconds, with 28.4% of patients stimulated at an
      OPT V-V delay of 0 milliseconds. The overall 6-month survival free of adverse
      events requiring invasive interventions was 81.8%. In the whole cohort, 6 months
      of CRT-D was associated with a significant decrease in New York Heart Association
      class, increase in the distance covered during the 6-minute hall walk, and
      improvement in QOL (each P < .0001). The effects of CRT-D on these end points
      were similar in both study groups. CONCLUSIONS: Cardioverter-defibrillator
      capabilities was associated with a significant alleviation of CHF symptoms,
      increase in functional capacity, and improvement in QOL. The optimization of the
      V-V delay conferred no additional benefit compared with simultaneous
      biventricular stimulation.

PMID- 16644336
TI  - Diagnostic conclusions from the EASI-derived 12-lead electrocardiogram as
      compared with the standard 12-lead electrocardiogram in children.
AB  - BACKGROUND: Fewer electrodes on more easily located places would facilitate
      electrocardiogram (ECG) recording. To investigate the possibility of simplifying
      ECG recording in children, we compared the diagnostic conclusions when
      interpreting standard versus EASI-derived 12-lead ECGs. Our hypothesis was that
      the variation of the interpretation of standard versus EASI-derived 12-lead ECGs
      was not greater than the intrareader variation of the interpretation of standard
      ECGs. METHODS: The study included 221 children. The 2 lead systems were recorded
      simultaneously. Two experienced pediatric cardiologists interpreted the ECGs.
      First, the reader interpreted a set of 221 ECGs with randomly allocated standard
      and EASI-derived 12-lead ECGs. Next, the reader interpreted the complementary ECG
      set without having access to the first set. Finally, the reader reinterpreted the
      standard ECGs from 98 children. RESULTS: The variation of the interpretation of
      standard versus EASI-derived 12-lead ECGs was only slightly larger than the
      intrareader variation of the interpretation of standard ECGs. CONCLUSIONS: For
      most of the electrocardiographic diagnoses, the conclusions from EASI-derived 12
      lead ECGs were similar to those from standard ECGs. These findings support the
      suggestion that the EASI lead system is a potential alternative to the standard
      ECG in children.

PMID- 16644337
TI  - Comparison of long-term mortality across the spectrum of acute coronary
      syndromes.
AB  - BACKGROUND: Data are sparse regarding comparative long-term mortality across the
      spectrum of patients presenting with acute coronary syndrome (ACS). METHODS: We
      identified all patients hospitalized with suspected myocardial ischemia in an
      urban academic hospital from 1991 to 1992. We compared presenting
      characteristics, treatment, and long-term mortality between patients with
      unstable angina (UA), minor myocardial damage (MMD), definite non-ST-elevation
      myocardial infarction (NSTEMI), and STEMI. RESULTS: Of 760 patients (mean age 68
      years, 35% women), 22% had UA, 35% had MMD, 26% had NSTEMI, and 17% had STEMI.
      During a mean follow-up of 9.5 years, unadjusted mortality was highest in
      patients with MMD and NSTEMI (mortality for UA 43%, MMD 68%, NSTEMI 62%, STEMI
      44%; P < .001). Patients with MMD and NSTEMI were older than patients with STEMI
      or UA, had more comorbid conditions (diabetes, prior myocardial infarction,
      congestive heart failure), and were less likely to receive aspirin,
      unfractionated heparin, or revascularization therapies during the index
      hospitalization. After multivariable adjustment for all significant covariates,
      mortality increased sequentially along the spectrum of ACS (hazards ratios for UA
      1.0 [referent], MMD 1.12 [95% CI 0.84-1.49], NSTEMI 1.28 [0.95-1.72], and STEMI
      1.52 [1.06-2.19]). CONCLUSIONS: Patients presenting with MMD and definite NSTEMI
      had a worse unadjusted long-term prognosis up to 10 years after index
      hospitalization than patients with STEMI. This mortality excess for MMD/NSTEMI
      was associated with more comorbid conditions and decreased use of basic therapies
      for ACS. After controlling for baseline differences, STEMI patients had the
      highest mortality.

PMID- 16644338
TI  - Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients
      -findings from the International Verapamil SR/Trandolapril Study (INVEST).
AB  - BACKGROUND: People of Hispanic origin are the fastest growing ethnic minority in
      the United States and often have hypertension and other comorbidities which
      increase the risk associated with coronary artery disease (CAD). METHODS AND
      RESULTS: An analysis of the 8045 Hispanic patients enrolled in INVEST was
      conducted, and comparisons were made to the 14,531 non-Hispanic patients. INVEST
      was a prospective, randomized, open, blinded end point study in CAD patients with
      hypertension. After 61,835 patient-years of follow-up, treatment with either a
      verapamil sustained release (SR) or atenolol antihypertensive strategy resulted
      in greater blood pressure control in Hispanic patients, and Hispanic patients
      were at significantly lower risk of experiencing a nonfatal myocardial
      infarction, nonfatal stroke, or death (hazard ratio [HR] 0.87, 95% CI 0.78-0.97).
      Hispanic ethnicity was associated with an increase (HR 1.19, 95% CI 1.04-1.36),
      and randomization to the verapamil SR strategy was associated with a decrease (HR
      0.85, 95% CI 0.76-0.95), in the risk of new-onset diabetes. Use of trandolapril
      in the verapamil SR strategy was associated with reduced risk of new-onset
      diabetes, whereas increasing doses of atenolol and hydrochlorothiazide in the
      atenolol strategy were associated with increased risk of new-onset diabetes.
      CONCLUSIONS: The Hispanic cohort of INVEST had better blood pressure control and
      lower risk of adverse cardiovascular outcomes compared with the non-Hispanic
      cohort. A verapamil SR strategy is an alternative to an atenolol strategy for the
      treatment of Hispanic patients with hypertension and CAD and can reduce the risk
      of new-onset diabetes.

PMID- 16644339
TI  - Electrocardiographic abnormalities predict deaths from cardiovascular disease and
      ischemic heart disease in Pima Indians with type 2 diabetes.
AB  - BACKGROUND: The association between electrocardiographic (ECG) abnormalities and
      deaths from cardiovascular diseases (CVD) and ischemic heart disease (IHD) has
      been reported in the general population, but there is little information
      regarding persons with type 2 diabetes. METHODS: Minor and major ECG
      abnormalities were identified and classified according to the Minnesota Code in a
      longitudinal study of 1605 Pima Indians aged > or =35 years with type 2 diabetes.
      Underlying causes of death were determined by review of all available clinical
      records, autopsy reports, medical examiners' findings, and death certificates.
      RESULTS: During a median follow-up of 14.1 years (range 0.1 to 33.8 years), there
      were 190 CVD deaths, 135 (71.1%) of which were attributable to IHD. The age
      adjusted CVD death rates in men with none, minor, and major ischemic ECG
      abnormalities were 7.3, 12.2 and 27.8, and in women, 4.3, 4.8 and 12.5 per 1000
      person-years, respectively. After adjustment for other co-variables in a multiple
      proportional hazards model, subjects with minor and major ischemic abnormalities
      on ECG had 1.22 (95% CI, 0.76-1.97) and 1.83 (95% CI, 1.21-2.76) times the CVD
      death rate, and 1.32 (95% CI, 0.70-2.50) and 2.12 (95% CI, 1.26-3.57) times the
      IHD death rate of those with no ischemic ECG abnormalities, respectively.
      CONCLUSIONS: The CVD and IHD death rates were higher in men and in subjects with
      major ischemic ECG abnormalities. Major ischemic abnormalities on ECG predicted
      death after accounting for other cardiovascular risk factors, including
      proteinuria.

PMID- 16644340
TI  - Increased cardiovascular risk associated with diabetes in Dallas County.
AB  - BACKGROUND: Diabetes mellitus is a major public health problem in the United
      States. We assess the prevalence of diabetes in Dallas County, quantify the
      association between diabetes and subclinical cardiovascular disease, and assess
      the use of evidence-based cardiovascular disease risk-modifying therapies.
      METHODS: This study uses data from 3392 participants aged 30 to 65 years from the
      Dallas Heart Study, a probability-based, multiethnic sample of residents living
      in Dallas County, Texas. Three primary outcomes were examined: (1) diabetes
      prevalence, (2) adjusted odds ratios for detectable coronary calcium stratified
      by diabetes diagnosis status, and (3) rates of use of evidence-based
      cardiovascular disease risk-modifying therapies among subjects with diabetes
      stratified by diabetes diagnosis status. RESULTS: The estimated prevalence of
      diabetes in Dallas County was 7.8%, with >40% of diabetic patients undiagnosed
      before participation in the Dallas Heart Study. Both previously diagnosed and
      previously undiagnosed diabetes were independently associated with the presence
      of coronary artery calcium (diagnosed: OR 3.55, 95% CI 1.56-8.05) (undiagnosed:
      OR 2.98, 95% CI 1.39-6.39). The rates of use of aspirin, angiotensin-converting
      enzyme inhibitors, and statins were suboptimal, and blood pressure and low
      density lipoprotein cholesterol targets were rarely met, especially among
      subjects with previously undiagnosed diabetes. CONCLUSIONS: Diabetes is prevalent
      and is associated with subclinical cardiovascular disease; this association is
      present even at the time of diagnosis. Despite the cardiovascular risk associated
      with diabetes, evidence-based risk-modifying therapies continue to be underused,
      and therapeutic targets remain unmet, especially among people unaware of their
      diabetes diagnosis.

PMID- 16644341
TI  - NT-probrain natriuretic peptide predicts complexity and severity of the coronary
      lesions in patients with non-ST-elevation acute coronary syndromes.
AB  - NT-probrain natriuretic peptide (NT-proBNP) has been associated with left
      ventricular (LV) dysfunction and adverse outcome in patients with non-ST
      elevation acute coronary syndromes (NSTEACS). However, the underlying
      pathophysiological mechanisms responsible for this association have not been well
      established. We sought to explore the relation between NT-proBNP levels and
      extension of coronary artery disease (CAD) and the presence of more complex and
      severe coronary lesions. METHODS: This prospective, multicenter angiographic
      substudy included 585 patients admitted with NSTEACS. Blinded measurements of NT
      proBNP and troponin T were performed at a median time of 3 hours after admission
      and analyzed centrally. Angiograms were read at a core laboratory by 2
      independent readers blinded to patient data. Complex coronary lesion was defined
      as the presence of at least one of the following: thrombus (+), TIMI flow < 2, or
      ulcerated plaque. RESULTS: NT-probrain natriuretic peptide levels increased
      proportionally as LV function decreased. The levels of NT-proBNP were directly
      related to the extent of the CAD. This association was maintained when we
      analyzed patients with normal LV function (n = 257). Patients with complex
      coronary lesions or those with at least one of its individual component had
      higher levels of NT-proBNP compared with those without complex coronary lesions.
      After adjusting for clinical and electrocardiographic variables and other
      biomarkers, positive troponin (OR 2.20, 95% CI 1.50-3.22, P < .0001) and
      supramedian NT-proBNP levels (OR 1.72, 95% CI 1.19-2.47, P = .003) independently
      contributed to the prediction of complex coronary lesions. CONCLUSION: In this
      study of patients with NSTEACS, NT-proBNP levels progressively increase with the
      severity of CAD and degree of LV dysfunction. Increased levels of NT-proBNP
      independently predict the presence of more complex coronary lesions.

PMID- 16644342
TI  - Effect of comorbidity on coronary reperfusion strategy and long-term mortality
      after acute myocardial infarction.
AB  - BACKGROUND: Chronic comorbidity is a prognostic determinant in ST-segment
      elevation myocardial infarction (STEMI). This study was aimed at determining to
      what extent this effect is independent or derives from adoption of different
      therapeutic strategies. METHODS: Seven hundred forty patients with STEMI
      hospitalized within 12 hours of symptom onset were enrolled in a population-based
      registry, in a health district comprising 1 teaching hospital with and 5 district
      hospitals without percutaneous coronary intervention (PCI) facilities. Three
      categories of increasing chronic comorbidity score (CS-1, n = 259; CS-2, n = 235;
      CS-3, n = 246) were identified from age-adjusted associations of comorbidities
      with 1-year survival. RESULTS: Higher CS was associated with lower direct
      admission or transferal rates to hospital with PCI. Coronary reperfusion therapy
      (PCI in 91.5% of 470 cases) was adopted less frequently (P < .001) in CS-3
      (41.9%) than CS-2 (69.4%) or CS-1 (78.8%). Compared with conservative therapy (n
      = 270), reperfusion therapy reduced 1-year mortality in the whole series not
      significantly (P = .816) in CS-1 but significantly in CS-2 (P = .012) and CS-3 (P
      = .001). This trend persisted after adjusting for age, Killip class, and acute
      myocardial infarction location (hazard ratio [HR] = 0.63 [95% CI 0.14-2.80], HR =
      0.62 [95% CI 0.31-1.25], and HR = 0.47 [95% CI 0.26-0.86] in CS-1, CS-2, and CS
      3, respectively). By hypothesizing an extension of coronary reperfusion therapy
      utilization rate in CS-2 and CS-3 to that in CS-1, from 21 (crude analysis) to 20
      (adjusted analysis) deaths were classified as potentially avoidable. CONCLUSION:
      Increased mortality in patients with chronic comorbidity and STEMI derives, at
      least in part, from underutilization of coronary reperfusion therapy, and might
      be reduced with a more aggressive therapeutic approach.

PMID- 16644343
TI  - Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of
      all-cause mortality, cardiac mortality, and myocardial infarction.
AB  - BACKGROUND: Matrix metalloproteinases and their inhibitors have been implicated
      in both vascular and ventricular remodeling, and in atherosclerotic plaque
      rupture. The prognostic value of plasma tissue inhibitor of metalloproteinase-1
      (TIMP-1) levels in patients with established or suspected coronary artery disease
      is unknown. METHODS: Tissue inhibitor of metalloproteinase-1 and matrix
      metalloproteinase-9 (MMP-9) levels, along with a number of other established
      biomarkers, were measured in 389 male patients undergoing coronary angiography at
      a Veterans Administration Medical Center. The patients were then followed
      prospectively for the occurrence of all-cause mortality, cardiac mortality, and
      myocardial infarction (MI). RESULTS: Follow-up data at 24 months were available
      for 97% of the patients. For the entire cohort of patients, TIMP-1 was the only
      biomarker to independently predict all-cause mortality and MI. In addition, the
      ratio of TIMP-1 to matrix metalloproteinase-9 was independently predictive of
      cardiac mortality at 24 months. The 24-month survival rates for patients in the
      lower quartile (< 66.5 ng/mL), interquartile (66.5-100 ng/mL), and upper quartile
      (> 100 ng/mL) of plasma TIMP-1 values were 95.3%, 89.3%, and 72.2%, respectively
      (P < .001). Furthermore, when patients with chest pain were risk stratified into
      those with and without an acute coronary syndrome, TIMP-1 remained an independent
      predictor of all-cause mortality in both subgroups. CONCLUSIONS: In a cohort of
      male patients undergoing coronary angiography, a single baseline determination of
      plasma TIMP-1 is independently predictive of the subsequent risk of death and MI.

PMID- 16644344
TI  - Platelet microaggregation inhibition in patients with acute myocardial infarction
      pretreated with tirofiban and relationship with angiographic and clinical
      outcome.
AB  - BACKGROUND: The relationship between the level of platelet aggregation inhibition
      in patients with acute myocardial infarction and their clinical outcome is
      unknown. METHODS: In patients with acute myocardial infarction included in the On
      TIME trial and transferred to the primary percutaneous coronary intervention
      (PCI) center of Zwolle, who were pretreated with tirofiban on top of
      acetylsalicylic acid and heparin, platelet microaggregation inhibition was
      assessed on admission and immediately after PCI, using the Sysmex K4500 (Sysmex
      Corp, Kobe, Japan) platelet microaggregation measurement. The level of platelet
      microaggregation inhibition was compared with angiographic and clinical outcome.
      Patients were randomized to early prehospital initiation of tirofiban or to
      initiation in the catheterization laboratory. Therefore, the effect of tirofiban
      on platelet microaggregation inhibition could additionally be determined by
      measuring baseline platelet microaggregation also at entrance into the hospital.
      RESULTS: In 412 (89%) of 463 patients, platelet microaggregation inhibition was
      measured after receiving tirofiban. There was no difference between the 4
      quartiles of the level of platelet microaggregation inhibition with regard to
      distal embolization, TIMI-3 flow and blush grade 3 after PCI, mean corrected TIMI
      frame count, ejection fraction, enzymatic infarct size, and percentage ST-segment
      resolution (P values .91, .97, .46, .94, .73, .33, and .72, respectively). The
      baseline platelet microaggregation inhibition in patients treated with tirofiban
      was 38% +/- 25% (mean +/- SD), and in the patients treated with placebo, 14% +/-
      22% (P < .001). CONCLUSIONS: We found no correlation between the level of
      platelet microaggregation inhibition after tirofiban and outcome, whereas only a
      modest increase in platelet microaggregation inhibition was observed after a
      commonly used dose of tirofiban.

PMID- 16644345
TI  - Handgrip-enhanced myocardial fractional flow reserve for assessment of coronary
      artery stenoses.
AB  - BACKGROUND: Fractional flow reserve (FFR) may yield false-negative results in up
      to 12% of lesions tested, and there is a zone of uncertainty at borderline
      values. METHODS: Forty-eight patients were investigated by means of dobutamine
      stress echocardiography (DSE), coronary angiography, and FFR assessment of 48
      coronary lesions before, during, and immediately after handgrip exercise.
      RESULTS: Mean FFR values were lower during and immediately after handgrip
      exercise as compared with baseline (0.86 +/- 0.09 vs 0.87 +/- 0.08 vs 0.88 +/-
      0.08, P < .05, respectively). The sensitivity of FFR < or = 0.75 for predicting
      myocardial ischemia on DSE was 17.6% before handgrip exercise, 52.9% during, and
      35.5% immediately after exercise. The specificity of FFR < or = 0.75 before,
      during, and immediate after exercise was 100%, 93.5%, and 96.8%, respectively. In
      10 patients, FFR values > 0.75 before handgrip became < or = 0.75 during or
      immediately after handgrip exercise (P = .01). All these patients had angina
      and/or DSE indicating ischemia in the territory of the vessel studied, and
      underwent coronary intervention. At 6 months follow-up, all patients were
      asymptomatic with negative DSE tests. CONCLUSIONS: The addition of handgrip
      exercise can significantly lower the FFR and potentially improve its ability to
      detect physiologically significant stenoses.

PMID- 16644346
TI  - Sestamibi single photon emission computed tomography immediately after primary
      percutaneous coronary intervention identifies patients at risk for large
      infarcts.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction results in TIMI 3 flow in most patients. However, despite
      TIMI 3 flow, some patients do not achieve adequate tissue perfusion and have
      large infarctions. Techniques that, in the acute setting, could identify these
      patients at increased risk would potentially enable specific interventions to
      enhance perfusion. The object of the present study was to test whether corrected
      TIMI frame count (CTFC), myocardial blush grade (MBG), ST-segment resolution, and
      myocardial perfusion imaging (MPI) can identify those patients who, despite
      successful treatment with primary PCI for ST-elevation myocardial infarction, are
      at risk for large infarcts. METHODS: In 61 patients with TIMI 3 flow after
      primary PCI, CTFC, MBG, ST-segment resolution, and quantitative MPI by technetium
      Tc 99m sestamibi single photon emission computed tomography were estimated
      immediately after primary PCI. Infarct size was assessed by peak lactate
      dehydrogenase (LDH) and by MPI after 3 months. RESULTS: Infarct size by MPI was
      12% (4, 23), and peak LDH was 1410 U/L (870, 2220); these measures correlated
      (rho = 0.80, P < .001). The acute perfusion defect predicted infarct size using
      either method (MPI rho = 0.88, P < .001; LDH rho = 0.77, P < .001); ST-segment
      residual correlated weakly to infarct size, whereas CTFC and MBG did not. In
      multivariate analysis, the acute perfusion defect was the only significant
      predictor of infarct size. CONCLUSION: Myocardial perfusion imaging performed
      immediately after successful PCI can identify patients at increased risk for
      large infarcts due to impaired tissue perfusion. Acute MPI might serve as a tool
      for early identification of patients, who, despite epicardial TIMI 3 flow, have
      inadequate tissue level perfusion.

PMID- 16644347
TI  - Elevated plasma N-terminal pro-brain natriuretic peptide levels in acute ischemic
      stroke.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is a neurohormone secreted mainly in
      the cardiac ventricles in response to volume expansion and pressure overload. The
      aim of this study was to assess plasma N-terminal proBNP (NT-proBNP) changes in
      acute ischemic stroke (AIS). METHODS: The study group consisted of 57 (37 women
      aged 64 +/- 12 years) patients who had their first AIS and no history or signs of
      cardiovascular disease. An age-matched control group was also included (n = 57,
      36 women aged 61 +/- 6 years). NT-proBNP, troponin I (TnI), and creatine kinase
      MB were evaluated. A thorough cardiovascular and neurological investigation,
      including imaging techniques and lesion size determination, was also performed.
      RESULTS: The log NT-proBNP peak levels, TnI, and creatine kinase-MB levels were
      significantly higher in AIS compared with controls (7.25 +/- 1.77 vs 3.48 +/-
      0.76 pg/mL, P < .0001; 0.76 +/- 0.54 vs 0.5 +/- 0.0 ng/mL, P < .001; 57 +/- 37 vs
      13 +/- 4 U/L, P < .001, respectively). The log NT-proBNP correlated positively
      with TnI (r = 0.29, P = .03) and heart rate (r = 0.41, P = .002), and negatively
      with left ventricular ejection fraction (r = -0.67, P < .0001). Patients with
      signs of marked myocardial ischemia and patients with insular cortex involvement
      had even higher NT-proBNP levels. After adjustment for relevant factors, the
      relation between the log NT-proBNP and AIS as well as insular cortex involvement
      was observed to be insignificant (P > .05 for both). CONCLUSIONS: Our results
      show that NT-proBNP plasma levels are significantly elevated in AIS and might be
      of clinical importance as a supplementary tool for the assessment of
      cardiovascular function in patients with AIS.

PMID- 16644348
TI  - Depression symptoms predict heart rate recovery after treadmill stress testing.
AB  - BACKGROUND: Altered autonomic nervous system (ANS) functioning may help to
      explain the relationship between depression and cardiac mortality. Heart rate
      (HR) recovery after the cessation of a treadmill stress test assesses ANS
      functioning and predicts mortality. This study examined the relationship between
      depression symptoms and HR recovery among patients entering phase II cardiac
      rehabilitation. METHODS: Two hundred sixty patients were assessed at the time of
      their enrollment in cardiac rehabilitation. Patients completed a ramped-protocol
      treadmill stress test, providing an assessment of exercise capacity and HR
      recovery at 2 minutes post exercise. Depression symptoms were measured using the
      Beck Depression Inventory. Other medical information was obtained by chart
      review. RESULTS: Patients with higher Beck Depression Inventory scores exhibited
      slower HR recovery after exercise. This remained true after controlling for age,
      sex, and beta-blocker usage. Controlling for exercise capacity rendered the
      relationship between depression score and HR recovery non significant, suggesting
      that exercise capacity may partly account for this relationship. CONCLUSIONS:
      These findings confirm that depression is characterized by dysregulation of the
      ANS and implicate impaired exercise capacity as a potential mechanism.

PMID- 16644349
TI  - Association of peripheral artery disease with treatment and outcomes in acute
      coronary syndromes. The Global Registry of Acute Coronary Events (GRACE).
AB  - BACKGROUND: National guidelines recommend the use of secondary prevention
      modalities for patients with peripheral artery disease (PAD) and coronary artery
      disease. The effect of prior PAD on the treatment and outcomes of patients with
      acute coronary syndromes (ACS), however, is not well characterized. The
      objectives of this study were to assess treatment practices and hospital outcomes
      in patients with ACS and prior PAD. METHODS: Data were analyzed from 41,108
      patients aged > or =18 years with ACS and enrolled in the large multinational
      GRACE between 1999 and 2004. RESULTS: Of the 41,108 patients, 4003 (9.7%) had
      prior PAD. Patients with PAD were older, more likely to be men, to have a variety
      of prior comorbidities, and to present with non-ST-segment elevation myocardial
      infarction and a higher Killip class than patients without PAD. Patients with PAD
      were less likely to be treated with effective cardiac medications than patients
      without PAD. At the time of hospital presentation, patients with prior PAD had
      low rates of use of beneficial cardiac medications, including angiotensin
      converting enzyme inhibitors, aspirin, beta-blockers, and lipid-lowering agents.
      Patients with PAD were significantly more likely to experience the composite
      hospital end point (death, shock, recurrent angina, stroke) than patients without
      prior PAD (adjusted OR 1.17; 95% CI 1.08-1.26). CONCLUSIONS: Patients with prior
      PAD received less aggressive treatment with proven cardiac medications during
      hospitalization for an ACS than patients without PAD. Utilization of beneficial
      medical therapies in patients with PAD before hospitalization with ACS was also
      less than optimal. Given the poorer hospital outcomes in patients with PAD, our
      findings suggest considerable opportunity to improve care for these high-risk
      patients.

PMID- 16644350
TI  - Assessment of patent foramen ovale in carcinoid heart disease.
AB  - BACKGROUND AND OBJECTIVE: Carcinoid syndrome may involve right carcinoid heart
      disease (CHD), secondary to the release of vasoactive substances. Left CHD is
      rare, as the inactivation of serotonin by the lung protects the left heart. We
      attempted to evaluate the prevalence of CHD and patent foramen ovale (PFO) with
      serial contrast transthoracic echocardiographic studies and to determine the
      markers of right and left CHD progression. METHODS: Forty-one consecutive
      patients with proved digestive endocrine tumor and carcinoid syndrome were
      prospectively enrolled. All patients underwent serial conventional and contrast
      transthoracic echocardiographic studies. Right and left CHD, PFO, radiological
      examinations, and biological carcinoid markers were systematically assessed.
      RESULTS: Left CHD was present in 5 patients at baseline and in 13 patients (32%)
      during follow-up (P = .03). The 13 patients with left CHD also had PFO, and no
      left CHD occurred without PFO (P < .0001). Right CHD was present in 16 patients
      (39%) at baseline and in 25 patients (61%) at the end of follow-up (P = .04). The
      prevalence of right and left CHD was significantly higher in patients with PFO
      (88% and 76%, respectively; P < .04). A progression of right and left CHD was
      present, respectively, in 19 and 9 patients but was mainly found in patients with
      PFO (15 and 9 patients; P < .0001). The main marker of CHD progression was the
      presence of PFO (odds ratio 44.2, 95% confidence interval 4.4-447.7; P = .001).
      CONCLUSIONS: PFO is a new marker of CHD progression and should be systematically
      assessed with routine contrast transthoracic echocardiography in patients with
      carcinoid syndrome to determine patients at high risk of CHD progression.

PMID- 16644351
TI  - Analysis of factors related to successful transcatheter closure of secundum
      atrial septal defects using the HELEX septal occluder.
AB  - BACKGROUND: The HELEX septal occluder is a new transcatheter atrial septal defect
      occlusion device. This study analyzes the data collected from the first US
      clinical trials with this device to determine the most significant factors in
      successful use of the device. METHODS: Tables of subsets of data were constructed
      in categories of possibly significant patient and device variables compared with
      important outcomes. Chi2 analysis was used to determine which variables had
      significant impact on outcomes. RESULTS: The device was successfully implanted in
      87% of patients (298/342). A major adverse event occurred in 5.8% (mostly device
      removal for various reasons). A significant residual leak persisted at 1 year in
      2.6%. A fracture of the wire frame occurred in 8%--all were asymptomatic and only
      1 required treatment. Overall composite success (no significant leak and no major
      adverse event) was seen in 91.5%. Patient age, body surface area, and device size
      had no significant influence on outcomes, except that wire frame fractures were
      more likely with the 35-mm device. Defect stretch diameter had the largest
      influence on outcomes, and implantation was possible in only 67% if the stretched
      diameter of the defect was >20 mm. Device-defect ratio also had a significant
      effect on delivery success and composite success. CONCLUSIONS: The HELEX septal
      occluder is best suited for small to moderate atrial septal defects with a
      stretch diameter <20 mm. Although composite success was achieved in 80% of
      patients when a device-defect ratio <1.6 was necessitated or elected, use of a
      device that provided a ratio >2 resulted in 95% composite success, and is
      recommended when possible.

PMID- 16644353
TI  - Optimizing techniques for musculoskeletal imaging of the postoperative patient.
AB  - Knowledge of imaging principles and parameter modifications of advanced imaging
      techniques--nuclear medicine, ultrasound, CT, and MR--aid musculoskeletal
      radiologists in selecting the appropriate examination for clinical questions;
      tailoring imaging parameters results in better image quality, thus more confident
      diagnoses. CT can evaluate for subtle fractures often better than conventional
      radiographs. Adjusting the area of interest, increasing the peak kilovoltage
      (kVp), and viewing images with postprocessing software allow better CT image
      quality. Proper modification of MR imaging parameters also provides useful
      information including visualizing the extent of osteolysis better than
      conventional radiographs. Fast spin echo imaging should be used, gradient echo
      avoided, and fast inversion recovery used instead of frequency-selective fat
      suppression.

PMID- 16644354
TI  - Postoperative imaging of the shoulder.
AB  - The management of the postoperative shoulder has improved, in part because of
      advances in imaging techniques. As disability and pain may occur or persist after
      shoulder surgery, it is imperative that clinicians have a detailed anatomic
      delineation before further treatment. Variations in surgical techniques, surgical
      distortion of native anatomy, and metallic artifacts decrease the accuracy of
      postoperative imaging. Pitfalls may be avoided with knowledge of postoperative
      alterations of the rotator cuff, labrum and capsule.

PMID- 16644355
TI  - Postoperative imaging of the hip.
AB  - The number and type of operative procedures involving the hip continue to
      increase, placing a greater emphasis on characterizing patient postoperative
      condition accurately. Optimal postoperative imaging evaluation may involve
      multiple modalities, including conventional radiography, radionuclide
      scintigraphy, and cross-sectional imaging. Many of the surgical procedures
      involve the placement of metallic joint replacements or fixation that can make
      the imaging evaluation of the postoperative anatomy challenging. Clinical
      examination of patients combined with the type of procedure performed direct the
      appropriate imaging evaluation; adequate clinical knowledge of these procedures
      and how to optimally image them provide an opportunity to attain the most
      accurate evaluation possible.

PMID- 16644356
TI  - Postoperative imaging of the knee.
AB  - The knee is a frequently injured joint and, thus, a common focus of operative
      intervention. As operative techniques and imaging modalities evolve, radiologists
      must be aware of the expected postoperative appearance after knee surgeries that
      are performed commonly and also must be comfortable recognizing complications
      encountered commonly in the immediate and delayed postoperative period. Drawing
      on the large amount of attention this subject has received of late in the
      radiologic and orthopedic literature, this article reviews the knee surgeries
      performed most commonly and the expected normal and most frequently encountered
      abnormal postoperative imaging findings with an emphasis on MR imaging.

PMID- 16644357
TI  - Postoperative imaging of the ankle and foot.
AB  - This article describes the relevant surgical detail and MR imaging appearance of
      common operations performed in the foot and ankle. To evaluate postsurgical
      patients critically, it is important to understand the primary clinical
      diagnosis, surgical treatment undergone, the interval since surgery, and
      patients' current clinical symptoms. Radiography is the most common imaging
      modality for evaluation of the postoperative ankle and foot. MR imaging may be
      useful for evaluating the soft tissues and osseous structures in the postsurgical
      foot and ankle.

PMID- 16644358
TI  - Imaging of the postoperative spine.
AB  - Spinal instrumentation techniques have expanded dramatically during the past
      several decades, but the search for the perfect operative approach and fixation
      system continues. Fixation devices are designed for the cervical, thoracic,
      lumbar, and sacral segments using anterior, posterior, transverse,
      videoarthroscopic, and combined approaches. In most cases, bone grafting also is
      performed, because instrument failure occurs if solid bony fusion is not
      achieved. Radiologists must understand the operative and instrumentation options.
      Knowledge of expected results, appearance of graft material, and different forms
      of instrumentation is critical for evaluating position of implants and potential
      complications associated with operative approaches and spinal fixation devices.

PMID- 16644359
TI  - Imaging of joint replacement procedures.
AB  - Joint replacement procedures have improved dramatically during the past 30 years
      fueled by the changes in techniques for hips and knees. Joint replacements in
      other anatomic regions also have become more popular. It is essential to
      understand the importance of pre- and postoperative imaging for evaluating
      patients. Preoperative images are used in concert with clinical data to select
      the appropriate patients and components. Postoperative imaging is critical for
      evaluating position and potential complications. Appropriate selection of imaging
      modalities is essential to provide optimal, cost-effective patient care.

PMID- 16644360
TI  - Postoperative infection.
AB  - Infectious disease complicating surgery involving the musculoskeletal system is
      one of the most important causes of postoperative morbidity and mortality. Timely
      detection and accurate localization of infectious processes have important
      clinical implications and are critical to appropriate patient management. Imaging
      studies can play an important role in the detection of infection and can help
      guide appropriate clinical management. The diagnosis of postoperative infection
      can be made by a variety of imaging modalities. This article reviews the various
      methods and modalities available for the detection of postoperative infection.

PMID- 16644361
TI  - Bone graft materials and synthetic substitutes.
AB  - Bone graft materials quickly are becoming a vital tool in reconstructive
      orthopedic surgery and demonstrate considerable variability in their imaging
      appearance. Functions of bone graft materials include promoting osseous ingrowth
      and bone healing, providing a structural substrate for these processes, and
      serving as a vehicle for direct antibiotic delivery. The three primary types of
      bone graft materials are allografts, autografts, and synthetic bone graft
      substitutes.

PMID- 16644362
TI  - Soft tissue tumors: post-treatment imaging.
AB  - As the radiologic evaluation of soft tissue masses has changed dramatically with
      the advent of MR imaging, the effect of MR imaging is even more striking in the
      assessment of patients after treatment. In cases of local tumor recurrence, MR
      imaging has become the standard of care. Using a few basic principles, even small
      local recurrences can be detected accurately, and recurrence can be distinguished
      from postoperative or post-treatment change. This review presents a fundamental
      approach to the evaluation of patients, following treatment for soft tissue
      tumors and highlighting MR imaging.

PMID- 16644363
TI  - A sick eye in a sick body? Systemic findings in patients with primary open-angle
      glaucoma.
AB  - Despite intense research, the pathogenesis of primary open-angle glaucoma (POAG)
      is still not completely understood. There is ample evidence for a
      pathophysiological role of elevated intraocular pressure; however, several
      systemic factors may influence onset and progression of the disease. Systemic
      peculiarities found in POAG include alterations of the cardiovascular system,
      autonomic nervous system, immune system, as well as endocrinological,
      psychological, and sleep disturbances. An association between POAG and other
      neurodegenerative diseases, such as Alzheimer disease and Parkinson disease, has
      also been described. Furthermore, the diagnosis of glaucoma can affect the
      patient's quality of life. By highlighting the systemic alterations found in
      POAG, this review attempts to bring glaucoma into a broader medical context.

PMID- 16644364
TI  - A review of anterior segment dysgeneses.
AB  - The anterior segment dysgeneses are an ill-defined group of ocular developmental
      abnormalities that share some common features and have a high prevalence of
      glaucoma. Current classification of what are and what are not anterior segment
      dysgeneses seems to vary and our knowledge of them is incomplete. As the limits
      of classical clinical medicine based on evaluation of signs and symptoms are
      reached, further advancements increasingly will come from molecular medicine and
      genetics. In this article we review the normal and abnormal development of the
      anterior segment (concentrating primarily upon neural crest derived dysgeneses),
      describe the various clinical entities produced and their diagnosis, and discuss
      the current knowledge of the genetics of these disorders. We also suggest a new
      approach to the classification of anterior segment dysgeneses, based upon the
      embryological contribution to the formation of the anterior segment of the eye.

PMID- 16644365
TI  - Progressive cone and cone-rod dystrophies: phenotypes and underlying molecular
      genetic basis.
AB  - The cone and cone-rod dystrophies form part of a heterogeneous group of retinal
      disorders that are an important cause of visual impairment in children and
      adults. There have been considerable advances made in recent years in our
      understanding of the pathogenesis of these retinal dystrophies, with many of the
      chromosomal loci and causative genes having now been identified. Mutations in 12
      genes, including GUCA1A, peripherin/RDS, ABCA4 and RPGR, have been described to
      date; and in many cases detailed functional assessment of the effects of the
      encoded mutant proteins has been undertaken. This improved knowledge of disease
      mechanisms has raised the possibility of future treatments for these disorders,
      for which there are no specific therapies available at the present time.

PMID- 16644366
TI  - Virtual reality in ophthalmology training.
AB  - Current training models are limited by an unstructured curriculum, financial
      costs, human costs, and time constraints. With the newly mandated resident
      surgical competency, training programs are struggling to find viable methods of
      assessing and documenting the surgical skills of trainees. Virtual-reality
      technologies have been used for decades in flight simulation to train and assess
      competency, and there has been a recent push in surgical specialties to
      incorporate virtual-reality simulation into residency programs. These efforts
      have culminated in an FDA-approved carotid stenting simulator. What role virtual
      reality will play in the evolution of ophthalmology surgical curriculum is
      uncertain. The current apprentice system has served the art of surgery for over
      100 years, and we foresee virtual reality working synergistically with our
      current curriculum modalities to streamline and enhance the resident's learning
      experience.

PMID- 16644367
TI  - The ticking time bomb.
AB  - A man with orbital myositis and optic neuritis tested positive serologically for
      multiple tick-borne diseases. Erlichiosis, babesiosis, and Lyme disease may occur
      together and affect the eye or orbit.

PMID- 16644368
TI  - A rare case of atypical chondroid syringoma of the lower eyelid and review of the
      literature.
AB  - A 46-year-old man presented with a painless firm mass in the eyelid margin of the
      left lower eyelid, which had been present for 9 years. Biopsy nine years
      previously had not established a diagnosis. We performed excisional biopsy of the
      lesion and lateral advancement skin flap for reconstruction of the skin defect.
      Histopathologic and immunohistochemical findings were consistent with atypical
      chondroid syringoma with eccrine differentiation. The systemic metastatic work-up
      was negative, and no recurrence or metastasis was present at 30-month follow-up.
      Chondroid syringoma is a rare skin tumor that occurs, very rarely, in the
      eyelids, especially the lower eyelid. Only 26 cases of chondroid syringoma in the
      periorbital area, including our case, have been reported, with various
      characteristics. Chondroid syringomas are classified as two types, the apocrine
      type characterized by tubular and cystic branching lumina lined by two layers of
      epithelial cells, and the eccrine type, which has small tubular lumina lined by a
      single layer of epithelial cells. The tumor can have benign, atypical, and
      malignant variants. Our patient had the atypical variant, which is characterized
      by benign cytological features, as well as the presence of infiltrative margins
      and/or satellite nodules. Even benign chondroid syringomas, if incompletely
      excised, can recur with malignant transformation; thus, complete excision and
      regular follow-up is recommended for all chondroid syringomas.

PMID- 16644369
TI  - Techniques of intraocular lens suspension in the absence of capsular/zonular
      support.

PMID- 16644370
TI  - Scleritis.

PMID- 16644390
TI  - Non-calcified plaques of coronary arteries with obvious outward remodeling
      demonstrated by multislice computed tomography.

PMID- 16644391
TI  - One month follow-up C-reactive protein may be a useful predictor of angiographic
      restenosis and long-term clinical outcomes after bare metal stent implantation.
AB  - We report C-reactive protein (CRP) measured 1 month after stenting was an
      independent predictor of angiographic restenosis, and patients with both elevated
      preprocedural CRP and CRP 1 month after stenting had the worst long-term clinical
      outcomes. Measurement of CRP during follow-up in addition to preprocedural CRP
      may improve risk stratification after coronary stenting.

PMID- 16644392
TI  - Viral myocarditis is a frequent cause of idiopathic dilated cardiomyopathy.

PMID- 16644394
TI  - [Status of lysosomal diseases amongst metabolic diseases].
AB  - Lysosomal diseases belong to the group of diseases which disturb the synthesis,
      catabolism or processing of complex molecules. These are the most common
      metabolic diseases, as they account for about one-third of all known metabolic
      diseases. They can be expressed as early as the intra-uterine stage of life, or
      appear after birth at any age, including during adulthood. They develop
      gradually, evolve independently of any intercurrent catabolic event and are
      independent of diet. Although they have long been associated with an inevitably
      fatal outcome, several can now be treated effectively, either by enzyme
      replacement therapy which increases catabolism of the overloaded substance thanks
      to an input of the deficient enzyme, or by drugs which reduce the synthesis of
      the overloaded substance.

PMID- 16644395
TI  - [Clinical aspects of early-stage neurological forms of Gaucher disease].
AB  - Pooling and in-depth analysis of cases taken from the literature and from French
      experience of patients suffering from early-stage neurological forms of Gaucher
      disease have made it possible to demonstrate the existence of more than two
      neurological forms which differ in terms of their natural history, clinical
      picture and response to enzyme therapy. The perinatal, lethal form is
      characterised by foetal and placental anasarca, foetal death, prematurity or life
      threatening distress at birth. The specific clinical signs include ichtyosis,
      muscle and tendon retraction and facial dysmorphism. Type 2 Gaucher disease
      affects infants and leads to death before the age of 2 years. Organ damage is
      characterised by the severity of pneumopathy. Neurological signs are of
      particular importance and include hyperextension of the neck and disorders
      affecting oculomotricity, sucking and swallowing. Most patients also develop
      episodes of apnoea which become increasingly lengthy and frequent as the disease
      progresses. Myoclonic epilepsy, which appears to be scarcely susceptible to
      enzyme therapy, and psychomotor regression are less common and are mainly seen in
      the rare cases of prolonged survival and in type 3 Gaucher disease.

PMID- 16644396
TI  - [Clinical study of the French cohort of Gaucher disease patients].
AB  - A census is currently being carried out of the French cohort of Gaucher disease
      patients. This article describes its preliminary results, obtained by analysing
      the records of 101 patients for whom clinical and laboratory data were accessible
      while they were receiving enzyme therapy. At the time of diagnosis, all patients
      presented with splenomegaly, 70% had asthenia and one in three was already
      affected by major bone damage. After 1 year of enzyme therapy, splenomegaly had
      diminished by half and the different scores (asthenia, bone pain and abdominal
      pain, etc.) had markedly improved, as had the biochemical markers. As for the 6
      patients affected by type 3 Gaucher disease and treated with enzyme therapy after
      the onset of neurological signs, a stabilisation or even some improvement of the
      disease was observed. In-depth study of the French cohort should make it possible
      to formulate consensus recommendations for the future, based on well-established
      data.

PMID- 16644397
TI  - [Current and future biochemical markers for Gaucher disease].
AB  - The biochemical markers secreted by Gaucher's cells are numerous, but none of
      those identified to date has offered all the expected qualities of a biomarker.
      Chitotriosidase and chemokine CCL18 are the most useful markers to follow enzyme
      replacement therapy. The identification of new biomarkers in the near future
      should enable a clearer understanding of the pathophysiology of this complex
      disease, which involves numerous cell processes.

PMID- 16644398
TI  - [Gaucher disease and chitotriosidase].
AB  - The course of chitotriosidase levels was studied in 4 patients with type 1
      Gaucher disease during treatment or during modifications to dosage or the
      frequency of administration. It proved to be a good marker of disease
      progression, before and during treatment. In the 4 patients treated by enzyme
      therapy, an increase in chitotriosidase levels before treatment and then its
      rapid and persistent decrease after treatment initiation closely followed the
      efficacy of the latter. When doses were reduced, the activity of chitotriosidase
      made it possible to check on the persisting efficacy of treatment and to detect
      at an early stage any insufficient dosage or poor compliance with treatment
      before any clinical complications arose. During any discontinuation of treatment
      (e.g. for pregnancy), its assay made it possible to plan a rapid resumption of
      treatment if necessary. For this reason, it is useful to assay this marker before
      initiating any treatment, and to regularly monitor changes in its levels and
      concentration, notably in the event of a dosage change or increase in the
      interval between intakes.

PMID- 16644399
TI  - Phenotype variations in Gaucher disease.
AB  - The Gaucher phenotype is very complex and it cannot be simply evaluated on the
      basis of blood counts or splenomegaly, but by the analysis of all disease
      compartments. To establish the diagnosis of Gaucher disease, biochemical assay of
      glucocerebrosidase activity is the most reliable method. However, it can be
      supplemented by molecular diagnosis, which may be helpful to predict the severity
      and the rate of progression of clinical manifestations. The genotype-phenotype
      correlations are very complex with a high inter-individual variability in the
      severity of clinical manifestations within a same genotype. Genetic modifiers may
      play an important role in determining the eventual Gaucher phenotype. Despite of
      some devastating complications, which can arise with advancing age, Gaucher
      disease worsen progressively in the majority of patients homozygous for the N370S
      mutation. The analysis of the data of the International Collaborative Gaucher
      Group registry should provide a better understanding of the natural history of
      the Gaucher disease.

PMID- 16644400
TI  - Therapeutic goals in Gaucher disease.
AB  - Evidence-based therapeutic goals have been developed by several European and
      American experts in Gaucher disease in order to attempt to reverse the entire
      Type 1 Gaucher phenotype, prevent complications, improve quality of life and
      prevent life-threatening complications. Patients with Gaucher disease will
      benefit by maximum enzyme replacement treatment (ERT) efficiency if it is given
      at the optimal time i.e. generally during the asymptomatic phase of the disease.
      Currently, Cerezyme is the standard of care for all severities of type 1 Gaucher
      disease due to its high efficiency at ameliorating bleeding tendencies, reversing
      organomegaly and part of skeletal damages and eliminating bone crises. ERT has
      also demonstrated a remarkable safety profile with tolerability at 3 years
      greater than 99%. Treatment of Gaucher disease is a long-life treatment that the
      patient should not interrupt without a careful monitoring of the disease
      evolution.

PMID- 16644403
TI  - Retrospective study of 23 pathologically proven cases of central nervous system
      tuberculomas.
AB  - INTRODUCTION: Extrapulmonary manifestations of tuberculosis involving the central
      nervous system (CNS) due to haematogenous spread are not a rare entity. It
      presents as meningitis or tuberculoma. Tuberculoma is a granulomatous
      inflammatory process mimicking a neoplasm radiologically, so usually a biopsy is
      performed. MATERIAL AND RESULTS: Our study consisted of 23 pathologically proven
      cases of tuberculomas between 1988 and 2003. Patients were discussed clinically,
      radiologically and histologically. Headache, fever, weight loss and weakness are
      the most common clinical manifestations. Our patient's ages vary from 3 to 67
      years with a mean of 31.8 years. Ninety-five percent of patients had bad social,
      economic and nutritional conditions. None of them were infected by human
      immunodeficiency virus (HIV). All patients had similar contrast-enhancing lesions
      radiologically. The majority of tuberculomas were located supratentorially. Only
      one patient presented two foci of (cerebral and cerebellar) tuberculomas.
      Nineteen tuberculomas were intracerebral; two were located in the cerebellum and
      one was intramedullary. Among those lesions, one cavernous sinus tuberculoma and
      one sellar tuberculoma were identified. Only two patients underwent stereotactic
      biopsy and 21 patients underwent surgical excision. Histopathologic examination
      revealed granulomatous inflammation with central caseous necrosis in all
      patients. DISCUSSION: Diagnosis of tuberculoma can be difficult, and in most of
      our cases, the clinical diagnosis was 'neoplasm'. For this reason, clinicians
      must always be aware of it and consider it in the differential diagnosis of
      central nervous system mass lesions.

PMID- 16644404
TI  - Epilepsia partialis continua in a patient with Behcet's disease.
AB  - Behcet's disease (BD) is a multisystemic, recurrent, inflammatory disorder of
      unknown aetiology. Neurological involvement is characterised either by primary
      parenchymal lesions or secondary to major vascular involvement. Seizures are
      rarely seen in BD and their occurrence can be related to seizure provoking
      factors or exacerbation of the disease. We experienced a case of neuro-BD
      presenting with subacutely developing mental and behavioral changes, followed by
      left dominant tetraparesis with bilateral pyramidal signs, fever and left hand
      focal motor seizures with elementery clonic motor signs which later evolved into
      right hand epilepsia partialis continua (EPC) of Kojevnikov. The seizures were
      very resistant to antiepileptic drugs and 8 months after neurological involvement
      the patient died. The EPC evolving after neurological involvement is associated
      with high mortality rate.

PMID- 16644405
TI  - Contralateral acute epidural haematoma following evacuation of a chronic subdural
      haematoma with burr-hole craniostomy and continuous closed system drainage: a
      rare complication.
AB  - Chronic subdural haematoma (CSDH) is one of the most frequent causes for
      neurosurgical intervention. Although the prognosis is generally good and
      treatment modalities are well established, some devastating intracranial
      haematomas can complicate its evacuation. The authors report here a case of an
      acute epidural haematoma occurring after evacuation of a contralateral chronic
      subdural haematoma (CSDH) with burr-hole craniostomy and continuous closed system
      drainage without irrigation. Since this is a rare, but potentially life
      threatening, complication, clinicians should suspect its occurrence when an
      unexpected postoperative course is demonstrated.

PMID- 16644406
TI  - Cortical myoclonus due to hypocalcemia 12 years after thyroidectomy.
AB  - Although seizures have been described in hypocalcemia, myoclonus has been rarely
      reported. We report the first case of a patient with hypocalcemic cortical
      myoclonus due to hypoparathyroidism following a previous thyroidectomy. The
      patient was an 84-year-old woman who presented with multifocal myoclonus, which
      was predominant in the upper extremities, neck, jaw, and facial muscles.
      Electrophysiological studies revealed enlarged somatosensory evoked potentials,
      cortical reflexes evoked by peripheral nerve stimulation, and a cerebral
      potential preceding myoclonic jerks determined by jerk-locked averaging. All
      these findings were consistent with cortical myoclonus. The myoclonic state
      disappeared as serum calcium level became normal. Hypocalcemia should be
      considered in patients who had had a thyroidectomy, even if it was performed more
      than 10 years previously.

PMID- 16644407
TI  - Neurobrucellosis mimicking cerebral tumor: case report and literature review.
AB  - We are reporting a case of neurobrucellosis that was clinically and
      radiologically indistinguishable from a cerebral tumor. The histological
      diagnosis was granulomatous encephalitis. The diagnosis was established by enzyme
      linked immunosorbent assay (ELISA), detecting high levels of Ig G and Ig M
      Brucella antibodies in the serum and the cerebrospinal fluid. We suggest that
      patients with granulomatous encephalitis, without a clear etiological agent,
      should be studied for Brucella.

PMID- 16644408
TI  - Oculopharyngeal somatic myopathy in a patient with a novel large-scale 3,399 bp
      deletion and a homoplasmic T5814C transition of the mitochondrial DNA.
AB  - We report a 65-year-old woman with a sporadic form of progressive oculopharyngeal
      somatic myopathy due to a novel large-scale 3,399 base pair (bp) deletion of the
      mitochondrial DNA (mtDNA) and co-occurrence of a homoplasmic T5814C transition.
      The onset of myopathy began from chronic progressive external ophthalmoplegia
      (CPEO) at age of 20 years. Bulbar weakness, neck and proximal limb paralysis,
      slowly progressed to eventual respiratory failure. The plasma levels of pyruvate
      (1.5 mg/dL) and lactate (20.2 mg/dL) were elevated. Muscle biopsy showed
      decreased enzymatic activity of cytochrome c oxidase, but no ragged-red fibers.
      Electron microscopy showed "parking-lot" paracrystalline inclusions in the
      enlarged mitochondria suggestive for mitochondrial myopathy. Sequencing of the
      whole mitochondrial genome of the patient's muscle and leukocytes showed 3,399 bp
      deletion of the mtDNA from nucleotide position 8,024 to 11,423 and a homoplasmic
      thymidine to cytosine transition at nucleotide position 5,814 of the tRNA(Cys)
      gene of mtDNA (T5814C). T5814C was absent in the white blood cells of the
      patient's daughter and in 205 normal controls. We conclude that a large-scale
      deletion may coexist with T5814C transition in patients with sporadic form of
      mitochondrial cytopathy manifested by slowly progressive oculopharyngeal somatic
      myopathy.

PMID- 16644409
TI  - Miliary tuberculomas of the brain: case report.
AB  - Tuberculosis (TB) of the central nervous system (CNS) is still prevalent in many
      developing countries. Tuberculoma is always considered in the differential
      diagnosis of enhancing intra-axial lesions of the brain. Brain tuberculomas can
      present in many different clinical and radiological patterns, disseminated or
      miliary brain tuberculomas are very rare. We describe the case of a 25-year-old
      immunocompetent female with miliary brain tuberculomas. She presented with a
      history of progressive headache and unsteady gait. Serial Magnetic resonance
      imaging (MRI) studies revealed growing, multiple small enhancing lesions in the
      brain, most lesions measured approximately 2mm in diameter, in both the
      supratentorial and infratentorial compartments. Her investigation failed to
      reveal any evidence of TB outside the CNS. Open biopsy revealed multiple
      caseating granulomas and mycobacterin tuberculosis was cultured. She improved
      clinically and radiologically after starting anti-tuberculous pharmacotherapy.
      The clinical course, radiological images and pathological studies of this patient
      are presented. In conclusion miliary brain tuberculomas are rare and unique
      clinical and radiological entity. It may affect immunocompetent individuals with
      no other signs of other systemic involvement.

PMID- 16644410
TI  - Probably anti-Tr associated paraneoplastic cerebellar degeneration as initial
      presentation of a squamous cell carcinoma of the lung.
AB  - Paraneoplastic cerebellar degeneration (PCD) is the most frequent paraneoplastic
      syndrome affecting the brain. Until now, anti-Tr associated PCD was only seen in
      patients with Hodgkin's disease. We report a male patient who presented with a
      progressive ataxia, affecting predominantly the lower limbs and a cerebellar
      dysarthria. Extensive diagnostic approach initially showed no evidence of tumor.
      The patient was found to have anti-Tr antibodies in his serum. Fourteen months
      after onset of symptoms a whole body PET-scan showed a pathological focus at the
      right hilus of the lungs. A mediastinoscopy was performed and peribronchial node
      sampling was done. The anatomopathological analysis revealed a non-well
      differentiated squamous cell carcinoma. This is the first report about the
      association between an anti-Tr associated PCD and squamous cell carcinoma.

PMID- 16644411
TI  - A case of Bickerstaff's brainstem encephalitis; the evidence of cerebellum
      involvement by SPM analysis using PET.
AB  - Although the clinical manifestations such as drowsiness, brisk reflexes, extensor
      plantar responses and hemisensory disturbance usually are considered to suggest
      Bickerstaff's brainstem encephalitis (BBE) rather than Miller Fisher syndrome
      (MFS), the nosological relationship between BBE and MFS has yet to be
      established. Herein, we report upon a 58-year-old man who showed ophthalmoplegia,
      ataxia and consciousness disturbance. In the absence of any abnormality on brain
      MRI, electrophysiological studies and SPM analysis using (18)F-FDG PET showed
      evidence of brainstem and cerebellum involvements.

PMID- 16644412
TI  - Cerebellar gliofibroma with numerous psammoma bodies.
AB  - A case of psammoma body rich gliofibroma is reported. Computed tomography (CT)
      showed a high-density mass without contrast enhancement in the right cerebellar
      hemisphere. Magnetic resonance images (MRI) demonstrated a mass with a mixture of
      high- and iso-intensity regions without meningeal attachment on both T1- and T2
      weighted images. Pathological examinations revealed a biphasic pattern consisting
      of tumor cells in sparce cellularity and dense fibrous connective tissue.
      Numerous psammoma bodies of uniform size were found in the stroma. The tumor
      cells expressed glial fibrillary acidic protein and S-100, but not p53, vimentin
      and EMA. This is the first report describing a case of psammomatous gliofibroma.

PMID- 16644413
TI  - Nonsurgical treatment of a patient with a Class III malocclusion.
AB  - A patient with a bilateral Class III molar relationship came to the Department of
      Orthodontics clinic at Case Western Reserve University. Our first choice for
      treatment was a combination of orthodontic therapy and orthognathic surgery. The
      patient, however, opted for a nonsurgical approach that took 34 months and
      involved the extraction of 4 first premolars and a remaining deciduous tooth, and
      Class III vertical elastics. Although orthodontic treatment was considered to be
      a second-line alternative, the results suggest that, for some surgical patients,
      orthodontic treatment alone might be a better choice because of the favorable
      cost/benefit ratio.

PMID- 16644414
TI  - AJO-DO Product Resource Guide.

PMID- 16644416
TI  - Early treatment 2005: deja vu all over again.

PMID- 16644417
TI  - The timing of early treatment: an overview.

PMID- 16644418
TI  - Patients' and parents' expectations from early treatment.

PMID- 16644419
TI  - Managing the patient with missing or malformed maxillary central incisors.

PMID- 16644420
TI  - Is early treatment for Class II malocclusion effective? Results from a randomized
      controlled trial.

PMID- 16644421
TI  - The timing of Class II treatment.

PMID- 16644422
TI  - Long-term adaptations to changes in the transverse dimension in children and
      adolescents: an overview.

PMID- 16644423
TI  - Maxillomandibular expansion: short-term relapse potential and long-term
      stability.

PMID- 16644424
TI  - Differential diagnosis and treatment planning for early mixed dentition
      malocclusions.

PMID- 16644425
TI  - Early treatment of Class III malocclusion: is it worth the burden?

PMID- 16644426
TI  - Impacted and ankylosed teeth: why, when, and how to intervene.

PMID- 16644428
TI  - American Society of Echocardiography minimum standards for the cardiac
      sonographer: a position paper.

PMID- 16644429
TI  - Effects of radial left ventricular dyssynchrony on cardiac performance using
      quantitative tissue Doppler radial strain imaging.
AB  - Our objective was to test the hypothesis that novel angle-corrected radial strain
      imaging can quantify left ventricular dyssynchrony associated with contractile
      impairment and improved with biventricular pacing. Eight open-chest dogs were
      studied by novel angle-corrected color-coded radial strain imaging and high
      fidelity pressure-conductance catheters recording pressure-volume loops. Heart
      rate was controlled by right atrial pacing and all timing intervals were
      corrected by R-R interval (corrected interval = measured interval/(R-R
      interval)(1/2)). Left bundle branch block, simulated by right ventricular free
      wall pacing, resulted in marked radial dyssynchrony, which we defined as maximal
      time difference between peak segmental strain, from 39 +/- 17 to 354 +/- 49
      milliseconds and stroke work decreased from 157 +/- 40 to 60 +/- 37 mJ, (P < .005
      vs baseline). Depression of contractility by high-dose esmolol (end-systolic
      pressure-volume relationship from 5.7 +/- 2.4 to 3.6 +/- 1.0 mm Hg/mL) was
      associated with augmented dyssynchrony to 388 +/- 53 milliseconds (P < .05 vs
      baseline right ventricular pacing). Biventricular pacing improved dyssynchrony to
      55 +/- 19 milliseconds and stroke work to 143 +/- 33 mJ (P < .05 vs right
      ventricular pacing). Changes in radial dyssynchrony correlated significantly with
      6-site average regional strain (r = -0.93 +/- 0.05 individually, r = 0.80
      overall) and stroke work (r = -0.88 +/- 0.12 individually, r = -0.82 overall).
      Angle-corrected radial strain imaging has clinical potential to quantify
      mechanical dyssynchrony and effects of biventricular pacing.

PMID- 16644430
TI  - Traditional and color M-mode parameters of left ventricular diastolic function
      during low-dose dobutamine stress echocardiography: relations to contractility
      reserve.
AB  - BACKGROUND: Cross-sectional studies reported that left ventricular (LV) systolic
      and diastolic functions are correlated. However, whether changes in wall-motion
      score index (WMSI) or 2-dimensional ejection fraction (EF) predict changes of
      Doppler parameters of LV diastolic function is unclear. METHODS: Patients with
      known or suspected history of coronary artery disease underwent assessment of LV
      systolic function (WMSI, EF) and diastolic function at baseline and during stress
      echocardiography by low-dose dobutamine (LDD) (peak infusion 10 microg/kg/min).
      Peak velocities of early (E) and late (A) LV filling waves and E wave
      deceleration time were measured according to standard protocol. E wave
      propagation rate (EVp) was assessed by color Doppler M-mode across the mitral
      valve. Tei index was calculated as: (A wave to E wave time - ejection
      time)/ejection time. Changes at LDD were calculated as: 100 x (value at LDD -
      value at baseline)/baseline. RESULTS: The study group comprised 66 patients, mean
      age 61 +/- 10 years, 80% men. Worse LV systolic function was associated with more
      severely impaired LV diastolic function both at baseline and at LDD. However,
      percent change of WMSI and change in EF did not correlate with percent change of
      EVp and E/E wave propagation rate, but with percent change of Tei index. At LDD,
      patients with myocardial viability did not show greater percent change of LV
      diastolic function parameters but significantly lower Tei index. CONCLUSIONS: In
      patients with suspected or known coronary artery disease, assessment of diastolic
      function reserve by LDD stress echocardiography using traditional and color M
      mode Doppler may add quantitative information on myocardial function beyond
      traditional assessment of contractility reserve by WMSI or EF.

PMID- 16644431
TI  - Isolated left ventricular diastolic dysfunction: implications for exercise left
      ventricular performance in patients without congestive heart failure.
AB  - OBJECTIVE: Clinical relevance of left ventricular (LV) diastolic dysfunction in
      the absence of congestive heart failure (CHF) and LV systolic dysfunction is not
      fully established. METHODS: Asymptomatic outpatients, sedentary, with
      cardiovascular risk factors but no history of cardiovascular events, underwent
      echocardiographic evaluation of LV structure and function by standard Doppler,
      color M-mode, and Doppler tissue methods, and exercise testing with simultaneous
      noninvasive assessment of LV stroke index and cardiac index. LV ejection fraction
      less than 50% and significant valvular disease or stress test suggestive of
      coronary disease were additional exclusion criteria. RESULTS: In 70 patients
      selected (40 +/- 10 years old, 63% men, 34% hypertensive, 34% diabetic, 4%
      diabetic and hypertensive, 11% with LV hypertrophy), LV diastolic dysfunction was
      detected in 26%, which was associated with hypertension, higher LV mass index,
      lower systolic function, lower peak exercise heart rate, and chronotropic reserve
      (all P < .05), and with lower peak exercise stroke index and cardiac index (both
      covariates adjusted P < .05), but not with lower peak exercise metabolic
      equivalents (P > .5). Abnormal LV relaxation was independently correlated with
      lower peak exercise cardiac index and stroke index (both P < .05). Peak exercise
      systolic and cardiac indices were comparable between patients with CHF risk
      factors (74%) versus those without. CONCLUSIONS: Isolated LV diastolic
      dysfunction was independently associated with lower peak exercise LV systolic
      performance in patients without CHF. Its diagnosis may provide a target for
      aggressive CHF risk management.

PMID- 16644432
TI  - Transesophageal echocardiographic acquisition of mitral annulus motion during
      monitoring of left ventricular function in anesthetized patients.
AB  - OBJECTIVE: We investigated the feasibility and reproducibility of transesophageal
      (TE) recordings of displacements and velocities of 4 sites of the mitral annulus
      in anesthetized patients. Correlations to transthoracic measures and influence of
      the respiratory cycle were also investigated. METHODS: A total of 24 patients
      without heart disease were included. Another 10 patients were enrolled for the
      reproducibility study. Systolic and diastolic velocities and amplitude of motion
      were extracted from color-coded Doppler tissue recordings. RESULTS: The
      reproducibility was not acceptable for the anterior site or for late diastolic
      velocities. Transthoracic values were higher than TE values. A somewhat higher
      displacement during inspiration in spontaneous respiration and during expiration
      in positive pressure ventilation was seen. CONCLUSIONS: The anterior site should
      be omitted when TE recordings of the mitral annulus are used. TE values are about
      15% lower than transthoracic values. There is no need to take the respiratory
      cycle into account.

PMID- 16644433
TI  - Right heart function in scleroderma: insights from myocardial Doppler tissue
      imaging.
AB  - To use Doppler tissue imaging to evaluate heart function and to predict
      rehospitalization rate in progressive systemic sclerosis, we studied 40 patients
      (limited in 24 patients, diffuse in 16 patients) with chest roentgenography,
      pulmonary function test, routine echocardiography, and myocardial Doppler tissue.
      Another 45 volunteers without any sign of heart failure served as the control
      group. Significant difference of echocardiographic parameters was found in peak
      transmitral early diastolic velocity, right ventricular (RV) ejection fraction
      (EF) (RVEF), pulmonary artery systolic pressure, and Doppler tissue parameters of
      the RV and septum (peak transmitral early diastolic velocity, P = .012; RVEF, P <
      .0001; pulmonary artery systolic pressure, P < .0001). The parameters derived by
      pulsed wave Doppler tissue decreased in RV, including peak systolic myocardial
      velocity (Sm), early diastolic velocity, late diastolic velocity, and myocardial
      performance index. RVEF and left ventricular EF were estimated by Simpson's
      method. RV-Sm could be used to identify RV failure. Receiver operating
      characteristic area under the curve for RV-Sm was 0.935. RV-Sm less than 11 cm/s
      indicted RVEF less than 40% with sensitivity of 87% and specificity of 86%.
      Contrary to expectation, pulmonary artery systolic pressure was not so well
      correlated with RV function. The frequency of admission was reverse correlated
      with decrement of RV-Sm in patients with RV-Sm less than 12 cm/s. We conclude
      that in progressive systemic sclerosis, RV systolic dysfunction is common and
      appears to be a result of pulmonary hypertension, disturbance of myocardial
      microcirculation, and myocardial fibrosis. Pulmonary hypertension was not well
      correlated with RV dysfunction; it suggested pulmonary hypertension was not the
      only cause of RV failure. Primary right heart involvement was the other possible
      cause. By myocardial Doppler tissue imaging, we can predict the frequency of
      hospitalization; it suggests simultaneous involvement of heart, skin, lung, and
      other organs. RV-Sm more than 12 cm/s predicted a decreased likelihood of
      readmission to the hospital.

PMID- 16644434
TI  - Impact of preload and afterload on global and regional right ventricular function
      and pressure: a quantitative echocardiography study.
AB  - BACKGROUND: Several quantitative echocardiographic measures of global and
      regional right ventricular (RV) function have been proposed, but knowledge of the
      impact of increases in preload and afterload is limited. METHODS: Seventeen
      healthy participants were exposed to increased preload by rapid infusion of 30
      mL/kg of saline over 15 minutes, and to increased afterload simulated in an 16-
      to 18-hour stay in a controlled hypoxic environment (fractional concentration of
      oxygen in inspired gas = 12.3%). Two-dimensional, Doppler, and Doppler tissue
      echocardiography evaluations were performed to evaluate global and regional RV
      function, with changes evaluated by paired analysis. RESULTS: Peak tricuspid
      regurgitation velocity increased in both conditions, whereas the RV end-diastolic
      diameter and acceleration time of the pulmonary forward flow only increased with
      increased preload and afterload, respectively. Estimates of RV function and
      contractility remained stable: no changes in the RV isovolumic acceleration (1.6
      +/- 0.6 vs 1.6 +/- 0.4 and 1.3 +/- 0.4 cm/s2) or tricuspid annular plane systolic
      excursion (2.5 +/- 0.4 vs 2.5 +/- 0.3 and 2.6 +/- 0.3 cm) were seen (baseline
      compared with increased afterload and preload, respectively). The RV index of
      myocardial performance was increased with increased afterload (0.26 +/- 0.08 vs
      0.34 +/- 0.13, P < .05), whereas no changes with increased preload were seen.
      Changes in loading conditions did not affect the regional strain. CONCLUSION:
      Moderate volume and pressure loading of the RV induces detectable changes in the
      RV pressure and morphology. Modern echocardiographic measures of systolic RV
      function seem stable with moderate increases in preload and afterload.

PMID- 16644435
TI  - Risk stratification in chronic heart failure: independent and incremental
      prognostic value of echocardiography and brain natriuretic peptide and its N
      terminal fragment.
AB  - BACKGROUND: It was the aim of this study to compare the prognostic impact of
      echocardiography and brain natriuretic peptide and its N-terminal fragment (NT
      proBNP) in patients with chronic heart failure (CHF). METHODS: In all, 73
      patients with CHF underwent conventional 2-dimensional/Doppler echocardiography
      and Doppler tissue analysis of systolic, early and late diastolic mitral annular
      velocities. The mitral filling pattern was classified as restrictive or
      nonrestrictive. NT-proBNP measurements were carried out on a bench-top analyzer.
      A cardiac event (rehospitalization caused by worsening CHF, cardiac death, urgent
      cardiac transplantation) was defined as combined study end point. RESULTS: During
      follow-up of 226 +/- 169 days, 27 patients had an event (rehospitalization
      because of CHF, n = 18; cardiac death, n = 7; urgent transplantation, n = 2). On
      multivariate Cox regression analysis, a restrictive filling pattern, NT-proBNP,
      the ratio of peak early diastolic mitral flow to mitral annular E' velocity were
      independent prognostic predictors. A risk stratification model based on the 3
      strongest independent predictors separated groups into those with good,
      intermediate, and poor outcome (event-free survival of 78%, 46%, and 0%,
      respectively). CONCLUSIONS: In patients with CHF, Doppler echocardiography,
      Doppler tissue imaging, and NT-proBNP provide independent and incremental
      prognostic information. A combined use of echocardiography and NT-proBNP may help
      to improve risk stratification in this patient population.

PMID- 16644436
TI  - The effect of carvedilol therapy on myocardial functional reserve in patients
      with advanced heart failure caused by nonischemic dilated cardiomyopathy.

PMID- 16644437
TI  - Efficacy of ultrasound-assisted stress testing using a hand-carried ultrasound
      device for diagnosis of coronary artery disease.
AB  - BACKGROUND: Exercise echocardiography is an effective means of noninvasively
      detecting coronary artery disease (CAD), and hand-carried cardiac ultrasound
      (HCU) devices are now being used to diagnose CAD in emergency rooms and at
      bedsides. OBJECTIVE: To compare the efficacies of exercise echocardiography with
      an HCU device (EchoCG-HCU) and exercise electrocardiography (ECG) in the
      diagnosis of CAD. METHODS: Fifty-eight patients underwent symptom-limited
      treadmill exercise testing. Two-dimensional echocardiographic images were
      obtained from standard parasternal and apical windows at rest and immediately
      after exercise using an HCU device (180 PLUS SonoSite Inc, Bothell, Wash). Wall
      motion was scored for each of 16 left ventricular segments using a 5-point
      grading system. The development of new or worsening wall motion was considered to
      be indicative of ischemia. RESULTS: When identifying CAD using exercise ECG, the
      sensitivity ws 63%, the specificity was 72%, and the diagnostic accuracy was 69%.
      By comparison, with exercise EchoCG-HCU the sensitivity was 68%, the specificity
      was 90%, and the diagnostic accuracy was 83%. Moreover, the specificity of
      exercise EchoCG-HCU was significantly higher than that of exercise ECG (p < .05).
      CONCLUSION: Exercise EchoCG-HCU is at least as useful as exercise ECG for
      diagnosing CAD.

PMID- 16644438
TI  - Feasibility of using a real-time 3-dimensional technique for contrast dobutamine
      stress echocardiography.
AB  - This is the first feasibility study using real-time 3-dimensional (3D) (RT3D)
      transthoracic contrast echocardiography with full-volume acquisition to evaluate
      left ventricular wall motion in patients undergoing dobutamine stress
      echocardiography. RT3D contrast and noncontrast 3D images were obtained at rest
      and peak dose dobutamine infusion and reviewed for image quality. A total of 14
      patients underwent complete rest and stress RT3D contrast and noncontrast
      imaging. Ultrasound contrast significantly increased the proportion of segments
      adequately visualized during rest and peak dobutamine infusion (91%-98%, P =
      .001, and 87%-99%, P = .001, respectively). With contrast there was almost
      complete concordance between observers (96.9% at rest and 98.2% at peak stress
      with almost no interobserver variability), whereas noncontrast studies had much
      lower agreement (84.4% at rest and 79.9% at peak stress with kappa values < 0.4).
      Three-dimensional contrast studies compared favorably with standard 2-dimensional
      imaging. Time for acquisition of all data sets with and without contrast was less
      than 90 seconds. RT3D dobutamine contrast stress echocardiography is feasible,
      greatly improves image quality compared with noncontrast images, and quickly
      acquires full data sets for subsequent analysis.

PMID- 16644439
TI  - Detection of residual infarct-related coronary artery stenosis and multivessel
      disease after thrombolysis: comparison between myocardial contrast
      echocardiography and single photon emission computed tomography.
AB  - BACKGROUND: Detection of residual infarct-related artery (IRA) stenosis and
      multivessel disease (MVD) after thrombolysis has important therapeutic and
      prognostic implications. Technetium 99m sestamibi single photon emission computed
      tomography (SPECT) is used for detection of flow-limiting coronary artery disease
      (CAD). Myocardial contrast echocardiography (MCE) is a new technique developed to
      assess CAD. We aimed to compare the relative accuracy of vasodilator stress MCE
      and SPECT for detection of IRA stenosis and MVD after acute myocardial
      infarction. METHODS: Accordingly, 72 patients underwent simultaneous MCE and
      SPECT 7 +/- 2 days after thromobolysis. Coronary angiography was performed in all
      patients. RESULTS: Of the 72 patients, 60 demonstrated significant myocardial
      viability of which 55 (92%) showed significant IRA stenosis (> 50%). MVD was
      present in 30 (42%) of the 72 patients. MCE was more accurate than SPECT for
      detection of both IRA stenosis (85% vs 62%, P = .02) and MVD (85% and 64%, P =
      .004). CONCLUSION: MCE was comparable to SPECT for the detection of IRA stenosis
      and MVD after thrombolysis.

PMID- 16644440
TI  - Noninvasive diagnosis of ischemic and nonischemic cardiomyopathy using coronary
      flow velocity measurements of the left anterior descending coronary artery by
      transthoracic Doppler echocardiography.
AB  - OBJECTIVES: The purpose of this study was to assess the feasibility and
      usefulness of coronary flow velocity measurements of the left anterior descending
      coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) to
      differentiate ischemic cardiomyopathy (ICM) from non-ICM in patients. BACKGROUND:
      ICM and non-ICM have similar 2-dimensional echocardiographic features, left
      ventricular dilatation, and diffuse wall-motion abnormalities. TTDE may be useful
      to differentiate ICM from non-ICM by detecting significant LAD stenosis based on
      LAD flow signal analysis. METHODS: TTDE was performed in 52 consecutive patients
      with left ventricular dilatation and diffuse wall-motion abnormalities of unknown
      origin. Peak and averaged systolic and diastolic flow velocities of the distal
      LAD flow could be recorded and measured from 44 patients (85%). Peak and mean
      diastolic/systolic velocity ratio (DSVR) were calculated. RESULTS: By coronary
      angiogram, 13 patients were given the diagnosis of ICM and 31 of non-ICM. Left
      ventricular end-diastolic and end-systolic volumes and ejection fraction were
      similar between ICM and non-ICM. On the other hand, peak DSVR (1.47 +/- 0.38 vs
      2.34 +/- 0.67, P < .0001) and mean DSVR (1.40 +/- 0.42 vs 2.24 +/- 0.61, P <
      .0001) were significantly lower in patients with ICM than non-ICM. Either peak
      DSVR less than 1.8 or mean DSVR less than 1.8 had a sensitivity of 77% and a
      specificity of 77% for detecting the presence of severe LAD stenosis and,
      therefore, the diagnosis of ICM. CONCLUSION: TTDE is a useful noninvasive method
      to differentiate ICM from non-ICM.

PMID- 16644441
TI  - A novel echocardiographic Doppler method for estimation of pulmonary arterial
      pressures.
AB  - BACKGROUND: Current noninvasive methods for estimating diastolic and mean
      pulmonary artery pressures (PAp) in children are cumbersome and have limited
      accuracy. We hypothesized that systolic PAp correlates with diastolic and mean
      PAp, and that this correlation can be used to estimate diastolic and mean PAp
      from Doppler flow data. METHODS: We recorded PAp in 112 patients 30 years or
      younger catheterized for heart failure, heart transplant, pulmonary hypertension,
      or congenital heart disease. We derived the relationship of systolic PAp to
      diastolic and mean PAp. We then applied these relations to systolic PAp measured
      by tricuspid regurgitation (TR) Doppler flow in a subset of 17 patients with
      pulmonary hypertension to predict mean and diastolic PAp, and correlated the
      results. RESULTS: An excellent linear relation was found between systolic PAp and
      both the diastolic and mean PAp measured at cardiac catheterization (r = 0.95, P
      < .0001; r = 0.98, P < .0001, respectively). The calculated diastolic PAp
      calculated from TR Doppler correlated well with invasive data (31 +/- 13 vs 30 +/
      11 mm Hg, respectively, not significant; r = 0.85, P < .0001) and surpassed
      existing methods that are based on pulmonary regurgitation for predicting
      diastolic PAp. Similarly, mean PAp calculated from TR Doppler flow correlated
      well with invasive data (r = 0.86, P < .0001). CONCLUSION: A strong linear
      relationship between systolic and diastolic PAp allows for easy and accurate
      noninvasive estimation of diastolic and mean PAp from TR Doppler flow.

PMID- 16644442
TI  - In vivo echocardiographic imaging of transplanted human adult stem cells in the
      myocardium labeled with clinically applicable CliniMACS nanoparticles.
AB  - OBJECTIVES: Intramyocardial transplantation of bone marrow-derived cells is
      currently under clinical evaluation as a therapy of heart failure. A major
      limitation of all clinical studies dealing with myocardial cell engraftment is
      the inability to track the fate of the transplanted cells. We present a
      clinically applicable technique using transesophageal echocardiography (TEE) of
      CliniMACS nanoparticle labeled transplanted CD133+ cells in ischemic hearts.
      METHODS AND RESULTS: CD133+ cells were isolated from human bone marrow by
      CliniMACS magnetic bead selection. Positive (5 x 10(6) cells) cells were
      transplanted into porcine ischemic myocardium (n = 6). Control animals (n = 5)
      received medium injection. TEE was performed to demonstrate the distribution of
      the cells during and 8 weeks after the procedure. Accumulations of labeled CD133+
      cells of adjacent injections in the myocardium were discriminatively identified
      by TEE. CONCLUSIONS: TEE is an elegant method for real-time documentation of
      successful transplantation and cell colony localization of magnetically labeled
      CD133+ cells in the ischemic myocardium. Our method should be of special interest
      for TEE-guided transcatheter injection of cells.

PMID- 16644443
TI  - A new window of opportunity in echocardiography.
AB  - BACKGROUND: Improvements in echocardiographic technology have made technically
      difficult studies a rare entity. However, physical barriers such as bandages,
      inability for patients to turn because of intubation, arterial lines, and organ
      and life support machines make echocardiographic imaging challenging. METHODS: We
      performed echocardiographic imaging from left and right posterior thoracic
      approach using acoustic properties of pleural fluid to assist in obtaining good
      imaging windows in patients who had pleural effusion (PE). In this study we
      describe one author's (T. Z. N.) experience with the mid to lower posterior
      thoracic window in 18 patients who had PE and in whom conventional transthoracic
      windows either provided suboptimal images or incomplete clinical information.
      RESULTS: The posterior approach allowed excellent differentiation of pericardial
      effusion versus PE, detection of pericardial disease and pericardial
      infiltration, and excellent endocardial border definition of left and right
      ventricle in those with poor anterior transthoracic windows. Native and
      prosthetic aortic valve gradients could be assessed adequately as a result of
      perfectly parallel Doppler alignment beam to left ventricular outflow tract and
      aortic valve. In addition, right posterior thoracic window provided views
      comparable with subcostal view and allowed visualization of inferior vena cava,
      right atrium, and liver. CONCLUSION: In patients with PE, imaging from low to
      midposterior thorax can provide additional diagnostic echocardiographic images
      and should be used in patients in whom conventional images are technically
      difficult or require additional information.

PMID- 16644444
TI  - Behcet's aortitis mimicking aortic valve endocarditis with subaortic
      complications.
AB  - Behcet's disease is a systemic inflammatory disease with rare cardiac
      involvement. We present a case of Behcet's aortitis involving the aortic and
      mitral valves with vegetations resembling aortic valve endocarditis with
      subaortic complications. Recurrent aortitis after aortic valve replacement
      resulted in an aortic pseudoaneurysm formation with moderate perivalvular aortic
      regurgitation that stabilized with immunosuppressive therapy and without the need
      for additional cardiac operation.

PMID- 16644445
TI  - Spontaneous retraction of an intramyocardial dissecting hemorrhage and multiple
      left ventricular thrombus formations in subacute myocardial infarction and
      antiphospholipid syndrome: a case report with long-term follow-up.
AB  - This report describes a 68-year-old patient with a subacute myocardial infarction
      and antiphosholipid syndrome. He developed an intramyocardial dissecting
      hemorrhage involving the left ventricular apex and multiple left ventricular
      thrombus formations, documented by contrast echocardiography and magnetic
      resonance imaging. By use of transthoracic echocardiography, spontaneous
      retraction of the dissecting hemorrhage could be detected. Severe coronary 3
      vessel disease was successfully treated by coronary artery bypass grafting.
      During follow-up of 16 months, the dissecting hematoma could not been detected.
      Under initiation of anticoagulant treatment with Coumadin, the patient was in
      stable clinical condition and improved in New York Heart Association class from
      III to II. The pathophysiology, diagnosis, and management of this potentially
      highly lethal complication is reviewed.

PMID- 16644446
TI  - Perforated periaortic valve abscess presents as acute pericarditis and patient
      died in transesophageal echocardiographic study.
AB  - Rupture of infective endocarditis-associated perivalvular abscess of left
      ventricular outlet leading to death is a rare complication of transesophageal
      echocardiography. We report a case of impending rupture periaortic valve abscess
      of left ventricular outlet that was initially diagnosed as acute pericarditis at
      the emergency department in which the patient suddenly collapsed during the
      ongoing procedure of transesophageal echocardiography. Emergency surgical
      intervention was performed, but in vain. Destructive aortic valve and rupture of
      the periaortic valve abscess were found.

PMID- 16644447
TI  - Esophageal dissection complicating transesophageal echocardiogram--the lesson to
      be learned: do not force the issue.
AB  - Transesophageal echocardiogram is a very safe procedure, however, it is not
      devoid of complications. We report a case of esophageal dissection complicating
      transesophageal echocardiogram in a 52-year-old man who was treated
      conservatively. Moreover, we review briefly the complications of transesophageal
      echocardiogram.

PMID- 16644448
TI  - Pulmonary regurgitant flow and detection of dip plateau.

PMID- 16644451
TI  - Preparations and prokinetics.
AB  - The evaluation of the importance of bowel preparations, prokinetics and postural
      tricks for bowel cleanliness, completeness of evaluation, and ultimately for the
      diagnostic yield of VCE is hampered by several factors. First, most studies are
      published in abstract form. Second, the methodological quality of the studies is
      rather low, because randomized comparisons are only a small minority. Third,there
      is no accepted and validated scale to evaluate bowel cleanliness. For all of
      these reasons, comparisons between studies are very difficult, and drawing
      general conclusions is almost impossible. As a consequence, at the Fifth
      International Conference on Capsule Endoscopy [9], only a limited measure of
      consensus could be reached on the fact that preparations/prokinetics probably
      improve the quality of small bowel cleanliness. It also was agreed that it is
      possible that preps/prokinetics improve GTT, SBTT and completeness of
      examination, and that keeping the patients recumbent in the right lateral
      position may shorten the GTT. It was noted, however, that the best type of
      preparation, and dose and time of administration remain to be determined.
      Additionally, data on prokinetics and postural tricks are insufficient to reach a
      firm conclusion. Unanswered questions concern the effect of medications on the
      diagnostic yield of VCE, whether prokinetics increase the miss rate, whether
      preparations/prokinetics cause adverse effects and the influence of medications
      on patient acceptance.

PMID- 16644452
TI  - Capsule endoscopy--transit abnormalities.
AB  - This article describes capsule endoscopy of the small bowel. It describes typical
      esophageal and gastric passage and the possibility of capsule retention. The
      article also highlights means of avoiding retention, diagnosing possible
      retention, and means of management.

PMID- 16644453
TI  - Capsule endoscopy: a meta-analysis for use with obscure gastrointestinal bleeding
      and Crohn's disease.
AB  - In this study, CE was superior to push enteroscopy and small bowel radiography
      for diagnosing small bowel pathology in patients who had OGIB, and its yield may
      be comparable to intraoperative endoscopy. Incremental yield of CE over push
      enteroscopy and barium radiography is greater than 30% for clinically significant
      findings, primarily because visualization of additional vascular and inflammatory
      lesions is possible by CE.CE was also found to be superior to small bowel barium
      radiography, colonoscopy with ileoscopy, CT enterography, and push enteroscopy
      for diagnosing nonstricturing small bowel CD. These findings primarily result
      from a marked improvement in yield with the use of CE over all other methods in
      patients who had established CD and were evaluated for a small bowel recurrence.
      Because this analysis was designed to evaluate trials that examined the yield of
      various methods for the diagnosis of OGIB and CD, it is unknown whether these
      results will translate into improved patient outcomes with the use of CE versus
      alternate methods. Randomized controlled trials will be necessary to clarify this
      issue.

PMID- 16644454
TI  - Bleeding update.
AB  - Obscure bleeding is a consolidated indication to CE, which when used as a first
      line exploration is the most efficient strategy as regards diagnosis in these
      patients. Patient selection and timing of the procedure are of paramount
      importance in the high diagnostic yield of CE. When integrated into a global
      patient care plan, CE is helpful in achieving effective decision-making
      concerning subsequent investigations and treatments. Although most studies appear
      to indicate a positive influence of CE diagnosis on clinical outcome of OGIB
      patients, large prospective trials are warranted to assess what is the most
      effective therapeutic strategy in patients with vascular lesions.

PMID- 16644455
TI  - Small bowel tumors.
AB  - WCE is a noninvasive diagnostic technique that visualizes the entire small
      intestine and identifies lesions in parts of the small bowel not reached by
      traditional endoscopy. Although further studies are needed to define the exact
      role of WCE for diagnosing and managing small bowel tumors, its sensitivity has
      been shown to be superior to PE and small bowel follow-through in regard to
      diagnosing patients who have obscure GI bleeding, the most common indication for
      capsule endoscopy in the authors' series of patients with documented small bowel
      tumors. As more material is published, capsule endoscopy likely will be confirmed
      to be the diagnostic procedure of choice in patients with suspected small bowel
      tumors.

PMID- 16644456
TI  - Portal hypertensive enteropathy.
AB  - The available data on the use of VCE in patients who have cirrhosis and portal
      hypertension are inadequate to reach a firm conclusion about the usefulness of
      this diagnostic tool in this patient population. In fact, only retrospective case
      series exist, in which the characteristics of the patients are heterogeneous in
      terms of severity of liver disease and of portal hypertension, etiology of
      cirrhosis, and indication for VCE. In addition, the controls included in the
      studies are heterogeneous or poorly described. In spite of this, it appears that
      in patients with portal hypertension, the small bowel frequently shows mucosal
      abnormalities. Such abnormalities appear to be particularly frequent in patients
      who have severe portal hypertension and in those with low hemoglobin levels. The
      clinical significance of these findings remains undefined, however, especially in
      view of the fact that small bowel lesions also have been found in about 10% of
      patients with arthritis not taking nonsteroidal anti-inflammatory drugs and in
      13.8% of healthy subjects [41,42]. Therefore,large prospective studies are needed
      to evaluate the prevalence and clinical significance of small bowel mucosal
      changes in patients who have cirrhosis. Such studies should compare patients who
      have cirrhosis with healthy subjects. A comparison between cirrhotic patients
      with a history of intestinal bleeding and bleeding patients without cirrhosis
      also would be interesting.

PMID- 16644457
TI  - The role of PillCam endoscopy in Crohn's disease: the European experience.
AB  - The European experience of wireless capsule endoscopy (WCE) inCrohn's disease
      (CD) is presented. Evidence from prospectivestudies comparing WCE with standard
      methods speaks in favor ofWCE as the method with the highest sensitivity for
      diagnosingsmall intestinal CD. WCE is likely to be helpful in diagnosing CD,in
      determining the extent of the disease, and in providing infor-mation on which of
      the current treatment approaches are specifi-cally effective within the small
      intestine. Although the invention ofthe patency capsule was helpful for
      diagnosing and characterizingsmall bowel strictures, the problem of capsule
      retention in CDpatients remains a controversial issue.

PMID- 16644458
TI  - Use of capsule endoscopy for established Crohn's disease.
AB  - There remains significant uncertainty regarding the role of capsule endoscopy in
      the setting of known inflammatory bowel disease (IBD). Capsule endoscopy should
      be considered for patients who have indeterminate colitis, who are failing
      medical therapy or who may require colectomy, who have truly unexplained symptoms
      based on standard endoscopy and radiography, and who have IBD and obscure
      bleeding. Although capsule endoscopy clearly detects small bowel pathology with
      greater sensitivity than other methods, the implications of these lesions are not
      fully understood. At this time, use of capsule endoscopy as a tool for the
      evaluation of mucosal healing or for prognostication of post-operative recurrence
      remains investigational.

PMID- 16644459
TI  - Capsule endoscopy in celiac disease: diagnosis and management.
AB  - Celiac disease occurs in about 1% of the population. Although diarrhea is the
      classical presentation, the diagnosis of celiac disease is frequently not
      considered as part of the differential diagnosis of a variety of different
      symptoms. It is,therefore, imperative that physicians who perform capsule
      endoscopy, and those who review the images, are aware of the variety of mucosa
      appearances inpatients who have celiac disease. In addition, studies are needed
      to determine the role of capsule endoscopy in the diagnosis and management of
      celiac disease.

PMID- 16644460
TI  - Monitoring nonresponsive patients who have celiac disease.
AB  - Because of the wide variations in the clinical presentation of celiac disease and
      because treatment exists that is effective in most cases, screening of the
      general population for celiac disease has been considered. There is still no
      evidence that patients who have symptom-free celiac disease are at increased risk
      of small intestinal lymphoma or other complications. Prevention of osteoporosis
      seems to be the strongest indicator for widespread screening today [22]. The
      major cause of failure to respond to a gluten-free diet is continuing ingestion
      of gluten, but other underlying diseases must be considered. Many different drugs
      (eg, anti-tumor necrosis factor [TNF]-alpha) have been used in patients who have
      RCD [23]. Steroid treatment has been reported to be effective even in patients
      who have underlying early EATL. Histologic recovery in patients who have celiac
      disease usually takes several months but can take up to 1 year, even if the
      patient remains on a strict gluten-free diet. Some patients report celiac-related
      symptoms for months after a single gluten intake. The definitions for RCD in
      literature vary. The authors consider the definition give by Daum and colleagues
      [24] suitable. They defined true RCD as villous atrophy with crypt hyperplasia
      and increased IELs persisting for more than 12 months in spite of a strict gluten
      free diet. If a patient is not responding well to a gluten-free diet, three
      considerations are necessary: (1) the initial diagnosis of celiac disease must be
      reassessed;(2) the patient should be sent to a dietician to check for errors in
      diet or compliance problems, because problems with the gluten-free diet are the
      most important cause for persisting symptoms; (3) other reasons for persisting
      symptoms (eg, pancreatic insufficiency, irritable bowel syndrome, bacterial
      overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis,
      protein-losing enteropathy,T-cell lymphoma, fructose intolerance, cavitating
      lymphadenopathy, and tropical sprue) should be considered. Other causes for
      villous atrophy are Crohn's disease, collagenous sprue, and autoimmune
      enteropathy. Abdulkarim and colleagues [25] examined 55 patients who had a
      diagnosis of nonresponsive celiac disease. He found that 6 did not have celiac
      disease, and25 still had some gluten ingestion.Tursi and colleagues [26] reported
      15 patients who had celiac disease with persisting symptoms. Because histology
      improved in all patients after several months, RCD was excluded. Of the 15
      patients, 10 had small intestinal bacterial overgrowth, 2 showed lactose
      malabsorption causing the described symptoms, 1 had mistakenly taken an
      antibiotic containing gluten, and 1 patient each had Giardia lamblia and Ascaris
      lumbricoides. Thus, other entities must be considered in patients who have celiac
      disease and ongoing symptoms. In a follow-up clinical trial, 158 patients who had
      celiac disease underwent follow-up small intestine biopsies within 2 years after
      starting a gluten-free diet. Eleven patients (7.0%) with persisting (partial)
      villous atrophy were considered to have RCD; 5 of them developed EATL [27].RCD
      type I is characterized by normal expression of T-cell antigens and polyclonal
      TCR gene rearrangement.RCD type II is characterized by an abnormal IEL phenotype
      with the expression of intracytoplasmic CD3e, surface CD103, and the lack of
      classic surface T-cell markers such as CD8, CD4, and TCR-alpha/beta. This clonal
      IEL population can be considered crypt IEL [24]. RCD II has a poor prognosis,
      which is a problem for therapy. Clonal TCR gene rearrangements and loss of T-cell
      antigens such as CD8 and TCR-beta in IELs may indicate the development of an EATL
      in patients who have RCD. The markers for an overt EATL are a positive stool
      blood test, increased lactate dehydrogenase, or beta2-microglobulin [24]. If an
      overt lymphoma is suspected, upper and lower endoscopy, an ear, nose, and throat
      work-up, CT scan, capsule endoscopy, and possibly double-balloon enteroscopy
      should be performed. Most reports of the difficulties in treating patients who
      have true RCE are casereports. Turner and colleagues [28] reported on an
      induction of remission by useof the anti-TNF-alpha antibody infliximab and
      maintenance with prednisoloneand azathioprine. Olaussen and colleagues [29] and
      Mandal and colleagues [30]tried a nonimmunogenic elemental diet. Gillet and
      colleagues [31] reported successful treatment of a patient who hadRCD using anti
      TNF-alpha antibodies (infliximab) for induction and azathioprinefor maintenance.
      Maurino and colleagues [32] studied seven consecutive patients diagnosed ashaving
      refractory sprue and no response to oral or parenteral steroids. Aftertreatment
      with azathioprine (2 mg/kg/d) and oral prednisone (1 mg/kg/d), fivepatients had a
      complete clinical remission. Two patients who did not respond totreatment at any
      time died. Goerres and colleagues [33] described 18 patients who had RCD, 10 of
      whomhad type I RCD, and 8 of whom had type II RCD. Treatment consisted
      ofazathioprine combined with prednisone for 1 year. Consistent with reports
      byother investigators, the response rates in the two groups differed. Eight of
      the10 patients who had type I RCD had a histologic response. Seven of the
      eightpatients who had type II RCD died, and six of the eight developed a
      lymphoma. At present there is no effective treatment for type II RCD.Fig. 3
      presents a proposed algorithm for monitoring patients who have ce-liac disease.

PMID- 16644461
TI  - Contraindications to capsule endoscopy: do any still exist?
AB  - In patients requiring WCE most contraindications are relative and the procedure
      can be performed safely in almost all clinical settings. The only true remaining
      contraindications to capsule endoscopy are obstruction/pseudo-obstruction and
      pregnancy. Informed consent of the risks and benefits, including NNE, should be
      discussed with all patients undergoing WCE examination.

PMID- 16644462
TI  - The economics of PillCam.
AB  - Evaluation of the economics of PillCam technology is in its infancy. Most studies
      of the use of the PillCam, both small bowel and esophageal, have focused only on
      the capsules' diagnostic characteristics. Although the results have compared
      favorably with other more invasive and sometimes less accurate modalities, the
      true cost effectiveness of PillCam is not yet fully known. The few cost
      effectiveness assessments performed suggest that PillCam compares favorably with
      traditional diagnostic methods in Crohn's disease and in screening for
      complications of GERD and for esophageal varices. The data included in these
      models are quite limited, however. Sensitivity analyses can permit assessment of
      a wide range of possibilities regarding cost and diagnostic efficacy. Still,
      these models need to be anchored by robust and reproducible data input. Large
      scale studies with long-term follow-up are needed. Capture of both direct and
      indirect medical costs accrued by using PillCam or other diagnostic tests in
      these studies will permit more robust economic analyses. As data accrue,they may
      give clinicians more confidence that PillCam use will realize economic savings
      and improve patient outcomes.

PMID- 16644463
TI  - Double-balloon endoscopy: from concept to reality.
AB  - The history of the double-balloon endoscope from conception to development and
      practical application has been described. The theory itself is quite simple, and
      there were opinions doubting its practicality at the early stage of
      development.Double-balloon endoscopes, however, are commercially available now.
      They have been used widely, and their usefulness has been recognized. When
      development of the double-balloon endoscope was progressing, development of
      capsule endoscopes also was progressing. The authors often heard opinions that,
      since capsule endoscopes were expected to become commercially available in the
      near future, it was out-of-date to devise a method to insert an enteroscope into
      the small intestine. The authors, however, believed that if the use of capsule
      endoscopes spread, the necessity of an enteroscope that can reach the entire area
      in the small intestine would not disappear, but become even bigger. If any
      abnormal finding is detected by a capsule endoscope, the necessity of enteroscopy
      for a detailed examination increases. This is being proven at present.

PMID- 16644464
TI  - Therapeutic uses of double-balloon enteroscopy.
AB  - In spite of initial skepticism toward the practicability of double-balloon
      enteroscopy, this technology will become an integral part of endoscopy and is
      likely to find expanded applications in the future. One strong reason to support
      this technique is the capacity to deliver endoscopic therapies, and thereby
      minimize aggressive surgical options. With increasing acceptance of capsule
      endoscopy by the medical community, more small-bowel lesions will be found and
      more directed endoscopic interventions will be needed. Like many new procedures,
      reimbursement issues will possibly prevent it from gaining well-deserved
      popularity. Unlike other common endoscopies, double-balloon enteroscopy is an
      expensive procedure. It requires fluoroscopy, extended anesthesia support, long
      procedure time, significant capital investment, and a team of threeor four people
      (endoscopist, anesthesiologist, nurse). Gastroenterologists and their patients
      will have to work together to convince insurance carriers that this isa valuable
      and cost-effective technology worthy of appropriate reimbursement.

PMID- 16644465
TI  - European experiences with push-and-pull enteroscopy in double-balloon technique
      (double-balloon enteroscopy).
AB  - This article describes research concerning push-and-pull enteroscopy. Clear and
      possible indications for this technique are highlighted.

PMID- 16644466
TI  - Twice-daily high-dose-rate brachytherapy for medically inoperable uterine cancer.
AB  - PURPOSE: Medically inoperable patients with uterine cancer pose a therapeutic
      challenge. We developed a twice-daily schedule of high-dose-rate brachytherapy
      (HDRB) after a single insertion procedure that required a hospitalization of 3
      days. METHODS AND MATERIALS: Favorable patients were offered brachytherapy alone,
      and all other patients received HDRB after pelvic external beam radiation therapy
      (EBRT). The prescribed dose was 7Gyx5 fractions and 4-5Gyx4-5 fractions for those
      treated after EBRT. HDRB was delivered with a b.i.d. schedule (4-6-h interval).
      RESULTS: Twenty-two patients (21 Stage I, 1 Stage IIB) were deemed medically
      inoperable. Sixteen patients received EBRT followed by HDRB, and six received
      HDRB alone. There were no procedural complications or significant acute toxicity.
      No thromboembolic events occurred within 30 days of the implant. CONCLUSIONS:
      This technique allows patients to be treated using a single procedure for
      insertion, with brief hospitalization for twice-daily HDRB.

PMID- 16644467
TI  - PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical
      failure: a study of 295 patients with a minimum 3-year followup.
AB  - PURPOSE: To assess the frequency and features of the PSA bounce phenomenon in a
      series of patients treated with permanent implant brachytherapy for prostate
      cancer, and to evaluate the percentage of cases in which this bounce could have
      mimicked a biochemical relapse according to the American Society for Therapeutic
      Radiology and Oncology consensus criteria. METHODS AND MATERIALS: From January
      1999 to December 2001, 295 patients were treated with a permanent prostate
      implantation (real-time technique, with free (125)I seeds) by the Paris Institut
      Curie/Hospital Cochin/Hospital Necker Paris group. Duration of followup is 40.3
      months (9-66 months). PSA level was reported at intervals not exceeding 6 months.
      Bounce was defined by temporary elevation in PSA level, followed by a spontaneous
      decrease. RESULTS: In our series, 161 patients (55%) showed a transitory PSA
      increase (bounce) of at least 0.1 ng/mL; 145 patients (49%) a bounce of 0.2
      ng/mL; 93 patients (32%) a bounce of 0.4 ng/mL; and 43 patients (15%) a bounce of
      at least 1 ng/mL. Mean PSA bounce was 0.8 ng/mL (0.1-4.1), and mean time to
      bounce was 19 months. Thirty-two patients (11% of total) presented three
      successive PSA increases, and therefore were to be considered as experiencing a
      biochemical relapse according to the American Society for Therapeutic Radiology
      and Oncology (ASTRO) consensus criteria. Among those 32 patients, 18 (56%)
      subsequently showed, without any treatment, a complete normalization of their
      PSA. In multivariate analysis, age <70 (p<0.0001) and D90>200Gy (p<0.003) were
      identified as independent factors for a PSA bounce of at least 0.4 ng/mL.
      CONCLUSIONS: The observed rate of 32% of patients showing a PSA bounce of at
      least 0.4 ng/mL in our series is in good agreement with what has been previously
      reported in the literature. Among 32 patients fulfilling the classical ASTRO
      criteria for a biochemical relapse, 18 (56%) subsequently showed a spontaneous
      PSA decrease, questioning the ASTRO consensus for the biochemical followup of
      patients undergoing permanent implant prostate brachytherapy.

PMID- 16644468
TI  - Migration of prostate brachytherapy seeds to the vertebral venous plexus.
AB  - PURPOSE: We report two cases of seed migration to the vertebral venous plexus
      after iodine-125 (I-125) transperineal interstitial permanent prostate
      brachytherapy. METHODS AND MATERIALS: Case 1: A 67-year-old Japanese man
      underwent percutaneous transperineal interstitial permanent prostate
      brachytherapy at our institution. Three months after brachytherapy, routine
      followup kidney-urinary bladder (KUB) radiography showed two seeds that had
      migrated to the pelvic area and were overlapped by sacral bone. It was very
      difficult to detect the seeds by visceral CT, because seeds were in contact with
      to vertebral bone, and seeds and bone were of the same CT value in visceral CT.
      But bone CT could distinguish seeds and bone, and it showed seed migration to the
      vertebral venous plexus in the sacral vertebral canal. Case 2: A 75-year-old
      Japanese man underwent percutaneous transperineal interstitial permanent prostate
      brachytherapy at our institution. The day after seed implantation, routine
      followup KUB radiography showed that a seed had migrated to the pelvic area and
      was overlapped by sacral bone. Bone CT clearly showed seed migration to the
      vertebral venous plexus in the vertebral canal in comparison with visceral CT.
      RESULTS: Seeds that have migrated to the vertebral venous plexus are difficult to
      be detected by visceral CT or KUB radiography. In visceral CT, it is difficult to
      distinguish seed and bone, especially when they are touching each other because
      they have the same CT value in visceral CT. It is therefore necessary to perform
      bone CT to detect such migrating seeds. CONCLUSIONS: To our knowledge, this is
      the first report of seed migration to the vertebral venous plexus after prostate
      brachytherapy. We thought that seeds migrate to the vertebral plexus via the
      pelvic venous pathway. If seed migration to the pelvic area and the overlapped
      sacral bone area is found after brachytherapy, bone CT should be performed,
      especially when it is difficult to detect the seed in visceral CT.

PMID- 16644469
TI  - Medical malpractice in the age of technology: how specialty societies can make a
      difference.
AB  - In the United States, medical malpractice litigation, and the rising cost of
      malpractice insurance, is a crisis that threatens to restrict patient access to
      high-risk services, especially obstetrics and certain surgical procedures.
      Radiation Oncology, though a small specialty, is very technologically oriented.
      Because the history of product liability and malpractice litigation in this
      country parallels the technologic revolution, practitioners of this specialty are
      clearly at risk for litigation. Because legislative relief is unlikely to be
      forthcoming in the near future, many specialty societies have assumed the
      responsibility for devising means to protect members from frivolous law suits,
      without compromising a patient's right to due process. To date, Radiation
      Oncology societies have not taken a leadership role in this movement, preferring
      instead to cede this responsibility to the American College of Radiology.
      Opportunities exist for specialty societies to define standards of care and
      establish guidelines for expert witness testimony. To date, the courts have been
      supportive of these efforts. Herein, we summarize some of the salient issues of
      the malpractice crisis facing Radiation Oncology and offer suggestions for change
      within the specialty to better address the malpractice problem.

PMID- 16644470
TI  - Commentary on "Medical malpractice in the age of technology: how specialty
      societies can make a difference (Anscher and Anscher)".

PMID- 16644471
TI  - Therapeutic targeting of pattern-recognition receptors.
AB  - Innate immune system could recognize the pathogen-associated molecular patterns
      by pattern-recognition receptors like Toll-like receptor (TLR) and nucleotide
      binding oligomerisation domain (NOD) protein. Information regarding the structure
      and signalling pathways of TLRs and NODs could provide opportunities for new
      therapeutic approaches to modulate the innate immunity. Therapeutic targeting
      could be done by prevention of ligand binding to leucine-rich repeats domains of
      receptors, blocking the interactions between receptors (like Toll/interleukin-1
      receptor domains of TLRs) and adaptors in signalling pathways, blocking the
      enzymes in signalling pathways, and immunostimulation with vaccine adjuvants.
      These therapeutic approaches could be useful in the treatment of different human
      diseases like immunological disorders, infections, and cancers. Further research
      on these receptors and their signalling pathways could help scientists to
      identify new candidates for therapeutic targeting.

PMID- 16644472
TI  - Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing
      Lewis lung carcinoma.
AB  - Phyllanthus urinaria, a widely used herb medicine in Asia, was tested for its
      anti-tumor effect in vivo for the first time. The anti-tumor activity in P.
      urinaria extract was evaluated by its effect on tumor developed in C57BL/6J mice
      with implantation of Lewis lung carcinoma cells. The oral administration of P.
      urinaria to mice caused significant inhibition of tumor development with lower
      occurrence rate and markedly reduced tumor size. Neither the total body weight of
      mouse nor the weights of organs including heart, lung, liver, spleen and kidney
      revealed any difference between two groups, suggesting limited in vivo cytotoxic
      effect of P. urinaria in mice. TUNEL assay demonstrated the increase of apoptosis
      in tumor sections prepared from P. urinaria-treated mice compared with control
      mice. It is worth of note that the neovascularization in tumor was inhibited in
      P. urinaria-treated mice, which implicated the potential anti-angiogenic effect
      of P. urinaria. Further study using an in vitro matrix-induced tube formation of
      HUVECs again confirmed the anti-angiogenic action of P. urinaria. P. urinaria
      exerted no inhibitory effect on the growth of HUVECs, however, the migration of
      HUVECs as analyzed using transwell assay was suppressed markedly by P. urinaria
      in a dose-dependent manner. All together, the present study indicated that P.
      urinaria extract is an anti-tumor and anti-angiogenic agent, which can be used
      safely in animals.

PMID- 16644473
TI  - Modulation of antigen-specific T cell response by a non-mitogenic anti-CD3
      antibody.
AB  - Suppression of T cell response is the key to enhance graft survival and control
      autoimmune diseases. A mitogenic anti-CD3 monoclonal antibody (mAb), OKT3, has
      been used for decades to control acute rejection in organ transplantation.
      Although effective, the clinical use was limited by its side effects, such as
      cytokine release mediated by T cell activation. A low mitogenic humanized OKT3
      with reduced FcR-binding (hgammaOKT3 Ala-Ala) was generated and tested in several
      clinical studies. Although hgammaOKT3 Ala-Ala demonstrated maintained efficacy
      and better safety it still activated T cells. To investigate if a non-mitogenic
      anti-CD3 mAb can be equally effective in immune suppression, a chimeric non-FcR
      binding anti-mouse CD3 mAb (anti-CD3 IgG2a Ala-Ala) was generated. Unlike the
      hgammaOKT3 Ala-Ala, the mouse IgG2a Ala-Ala anti-CD3 mAb did not induce T cell
      activation as measured by proliferation, cytokine production and apoptosis.
      Nevertheless, the IgG2a Ala-Ala anti-CD3 mAb was equally effective in the
      inhibition of antigen-specific CD4+ T cell activation in vitro to that of the
      mitogenic anti-CD3 mAb (Anti-CD3 IgG2a). In vivo, the IgG2a Ala-Ala anti-CD3 mAb
      only induced transient reduction of peripheral and spleen T cells and did not
      trigger detectable cytokine release. Nonetheless, this non-mitogenic anti-CD3 mAb
      significantly prolonged islet graft survival as effectively as the mitogenic anti
      CD3 mAb in an allogenic islet transplantation model. These results demonstrated
      that a non-mitogenic anti-CD3 mAb could be used as an effective immune modulator.
      It may also indicate that a true non-mitogenic version of OKT3 could further
      improve its safety profile for clinical use.

PMID- 16644474
TI  - Estrogen down-regulates nicotine-induced adhesion molecule expression via
      nongenomic signal pathway in endothelial cells.
AB  - Although gonadal hormone mostly causes genotropic actions through the members of
      nuclear receptor family, it also can regulate these actions via membrane
      receptor. To explore the possibility of plasma membrane estrogen receptors (mER)
      mediating genotropic events, we have investigated estrogen's effect on nicotine
      stimulated adhesion molecule expression and evaluated whether this effect depends
      on calcium, MAPK signal pathway. Fluorescence Spectroscopy analysis of Ca2+ from
      human umbilical vein endothelial cells (HUVECs) showed through mER, estrogen
      induced a rapid rise of intracellular free Ca2+ concentration and this rise could
      not be inhibited by tamoxifen (classic ER inhibitor). In the context of nicotine
      stimulating, however, estrogen attenuated phosphorylation of mitogen-activated
      protein kinase (MAPK) family members, extracellular signal regulated kinase 1/2
      (ERK1/2), p38 but not c-Jun-N-terminal kinase (JNK) in HUVECs and this effect
      could not still be prevented by tamoxifen. In the meantime, estrogen also down
      regulated surface/soluble vascular cell adhesion molecule (VCAM-1, sVCAM-1) and
      endothelial selectin (E-selectin, sE-selectin) levels, which was not abolished by
      tamoxifen either. Moreover, calcium chelator BAPTA, ERK1/2 inhibitor PD98059, p38
      inhibitor SB203580 significantly reduced the production of nicotine-activated
      surface/soluble VCAM-1 and E-selectin and both of the remained levels were no
      longer regulated by estrogen. Our study here provides the information of decrease
      effect of mER-mediated estrogen through Ca2+ and ERK1/2, p38 MAPK signaling
      pathway on nicotine-stimulated expression of surface/soluble VCAM-1 and E
      selectin in HUVECs.

PMID- 16644475
TI  - A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion
      lowers production of tumor necrosis factor-alpha and interferon-gamma in mice.
AB  - In a wide range of human diseases of inflammatory nature like Crohn's disease,
      pathology is mediated in part by pro-inflammatory cytokines like tumor necrosis
      factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic
      antidepressant bupropion, in wide use worldwide to treat depression in humans for
      a decade now, profoundly lowers levels of TNF, interferon-gamma, and interleukin
      1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model.
      Mice challenged with an otherwise lethal dose of LPS were protected by bupropion
      and levels of the anti-inflammatory cytokine interleukin-10 were increased.
      Previous data in rodents and humans indicate antidepressant effects of bupropion
      are mediated by its weak reuptake inhibition of norepinephrine and dopamine.
      Concordant with this, TNF suppression by bupropion in our mouse LPS model was
      largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not
      by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with
      intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either
      beta-adrenoreceptors or D1 dopaminergic receptors result in increased cAMP but
      stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress
      TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1
      receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is
      well tolerated also in non-psychiatric populations and has less risk with long
      term use than current anti-inflammatory, immunosuppressive or TNF suppressive
      treatments such as prednisone, azathioprine, infliximab, or methotrexate. New
      anti-inflammatory treatments are needed. We believe a new chapter in
      antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's
      use for this in humans should be explored.

PMID- 16644476
TI  - Enhancement of cytokine-mediated NF-kappaB activation by phosphatidylinositol 3
      kinase inhibitors in monocytic cells.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays crucial
      roles in inflammation and immunity. Understanding the positive and negative
      regulation of NF-kappaB activity is therefore of fundamental importance. A few
      previous studies reported that inhibition of the phosphatidylinositol 3-kinase
      (PI3K)-Akt pathway enhances lipopolysaccharide (LPS)-induced activation of NF
      kappaB. However, many aspects of the PI3K negative regulation of NF-kappaB
      activation remain to be clarified. The present study was conducted to shed light
      on cell-type specificity, stimulus specificity, and upstream mechanisms of the
      enhanced NF-kappaB activation by PI3K inhibitors. Gel shift assays showed that
      LY294002 (LY29) potently increased interleukin (IL)-1-induced NF-kappaB DNA
      binding in human monocytic THP-1 cells. Moreover, another PI3K inhibitor 3
      methyladenine also strongly enhanced IL-1-induced NF-kappaB DNA binding, while
      LY303511, an inactive analogue of LY29, did not increase the NF-kappaB DNA
      binding. Compared with LY29, wortmannin (WM) effected only a marginal enhancement
      of NF-kappaB DNA binding. LY29 treatment also augmented tumor necrosis factor
      (TNF)-mediated NF-kappaB DNA binding. Furthermore, LY29, but not WM, increased
      cyclooxygenase (COX)-2 mRNA expression by IL-1 or TNF in THP-1 cells. Likewise,
      prostaglandin E2 production by IL-1 was increased by LY29, but not by WM. Western
      blot analysis demonstrated that IkappaB kinase (IKK) activation as well as
      IkappaB-alpha degradation and NF-kappaB nuclear translocation was elevated by
      LY29 and WM. Among the tested cell lines (HL-60, ECV304, Hep-2, and Molt-4), only
      HL-60, a promyelocytic cell line, showed enhanced NF-kappaB DNA binding by LY29.
      These results suggest that pharmacological inhibition of PI3K enhances the NF
      kappaB-activating pathways by IL-1 through augmentation of IKK activation in
      myeloid/monocytic cells and the NF-kappaB enhancement is more robustly achieved
      by LY29 than by WM.

PMID- 16644477
TI  - Suppression of interleukin-6 production in macrophages by furonaphthoquinone NFD
      37.
AB  - Furonaphthoquinone compounds have been reported to exhibit anticancer,
      antibacterial and antiviral properties. The molecular basis for these diverse
      properties is not known. 2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone
      [2,3-b]furan-4,9-dione (NFD-37) is a synthetic furonaphthoquinone compound. In
      the present study, NFD-37 was found to inhibit interleukin (IL)-6 production in
      lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7. Further, NFD-37
      attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS
      induced IL-6 promoter activity. Since nuclear factor (NF)-kappaB activation has
      been shown to play a key role in LPS-induced IL-6 expression, the effect of NFD
      37 on LPS-induced NF-kappaB activation was further analyzed. NFD-37 exhibited a
      dose-dependent inhibitory effect on LPS-induced phosphorylation of inhibitory
      kappaB alpha protein (IkappaB alpha), and subsequently inhibited LPS-induced
      IkappaB alpha degradation as well as NF-kappaB transcriptional activity. In
      another experiment, NFD-37 inhibited both IL-6 promoter activity and NF-kappaB
      transcriptional activity elicited by an expression vector encoding IkappaB kinase
      beta. Taken together, NFD-37 down-regulated LPS-induced IL-6 expression through
      NF-kappaB activation, which could provide a pharmacological basis for the anti
      inflammatory properties of furonaphthoquinone analogs.

PMID- 16644478
TI  - Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids
      and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear
      cells from patients with antineutrophil cytoplasmic antibody-associated
      vasculitis and nephrosis.
AB  - Successful immunosuppressive therapy is critical for the treatment of patients
      with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and
      nephrosis. However, a considerable number of patients have shown clinical
      resistance to therapy. Bacterial infection might influence the clinical response
      of patients to immunosuppressive drugs, but few studies have been carried out to
      investigate the effect of bacterial superantigens on the efficacy of the drugs in
      these patients. We evaluated the suppressive efficacy of prednisolone,
      methylprednisolone, cyclosporine, and tacrolimus on the blastogenesis of PBMCs
      obtained from 12 ANCA-associated vasculitis patients (ANCA patients), eight
      patients with nephrotic syndrome, and eight healthy subjects. PBMC-stimulation
      index was calculated from the formula: [3H]thymidine incorporated in the presence
      of stimulant (dpm)/[3H]thymidine incorporated in the absence of stimulant (dpm).
      In vitro drug concentrations giving 50% inhibition (IC50s) of PBMC blastogenesis
      stimulated with concanavalin A (con A) or toxic shock syndrome toxin 1 (TSST-1)
      derived from Staphylococcus aureus (S. aureus) were calculated. The IC50 values
      for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher
      than those evaluated in con A-stimulated PBMCs in both ANCA patients and
      nephrosis patients (p<0.012-0.044). Whereas, the IC50 values for these
      immunosuppressive drugs, except methylprednisolone, were not significantly
      different between con A- and TSST-1-stimulated PBMCs in healthy subjects. The
      stimulation index was not significantly different between the con A- and TSST-1
      stimulated PBMCs in either of the subject groups. These observations raise the
      possibility that TSST-1 induced by S. aureus infection attenuates the clinical
      efficacy of glucocorticoids and calcineurin inhibitors in ANCA patients and
      nephrosis patients.

PMID- 16644479
TI  - Decreased intracellular TLR9 confers hyporesponsiveness of RAW264.7 cells to
      subsequent CpG ODN challenge.
AB  - Low-dose CpG ODN pretreatment is known to induce effective protective immunity
      against acute infectious diseases. In the present study, using primary murine
      peritoneal macrophages and the macrophage-like cell line, RAW264.7, we
      investigated whether low-dose CpG ODN pretreatment would induce
      hyporesponsiveness in response to a subsequent high-dose CpG ODN challenge and
      further investigated the molecular mechanisms underlying this event. Our results
      showed that pretreatment with a low dose of CpG ODN inhibits TNF-alpha production
      stimulated by later high-dose CpG ODN stimulation in a dose- and time-dependent
      manner. Interestingly, anti-mouse TLR9 blocking antibody added prior to CpG ODN
      pretreatment did not affect TNF-alpha release, but antibody added after CpG ODN
      pretreatment augmented the pretreatment effect of CpG ODN. This difference
      suggests that cell-surface TLR9 is indeed functional on activated cells. Flow
      cytometry revealed that low-dose CpG ODN pretreatment decreased cell-surface
      binding and internalization of a subsequent high-dose stimulation, suggesting
      that decreased internalization of succeeding CpG ODN is associated with reduced
      TNF-alpha release. Although both intracellular and cell-surface TLR9 expression
      are observed, low dose of CpG ODN pretreatment increased only cell-surface TLR9
      levels. Importantly, low-dose CpG ODN pretreatment also significantly inhibited
      the activation of NF-kappaB, an important downstream regulator of various
      proinflammatory cytokines. In summary, our results demonstrate that suppression
      of TNF-alpha production by low dose of CpG ODN pretreatment correlates with
      decreased binding and internalization of subsequent CpG ODN, decreased
      intracellular content of TLR9, and inhibition of NF-kappaB activation.

PMID- 16644480
TI  - cAMP-PKA signaling pathway regulates bone resorption mediated by processing of
      cathepsin K in cultured mouse osteoclasts.
AB  - Cathepsin K (Cat K) is the major cysteine protease expressed in osteoclast and is
      thought to play a key role in matrix degradation during bone resorption. It is
      shown that the intracellular maturation of Cat K was prevented by the cAMP
      antagonist, Rp-cAMP, and the protein kinase A (PKA) inhibitors of KT5720 and H89.
      In contrast, forskolin, an adenylate cyclase agonist, rather induced Cat K
      processing and maturation in osteoclast. Furthermore, to determine whether Cat K
      processing and maturation signaling involves protein kinase C (PKC), mouse total
      bone cells were treated with calphostin C, a specific inhibitor of PKC, however,
      no effect was observed, indicating that PKC calphostin C did not affect to
      osteoclast-mediated Cat K processing and maturation in osteoclast. Thus, it is
      indicated that the cAMP-PKA signaling pathway regulate Cat K maturation in
      osteoclast. Since secreted proenzymes have the potential to reenter the cell via
      M6P receptor, to prevent this possibility, we tested cAMP antagonist Rp-cAMP and
      the PKA inhibitors KT5720 and H89 in the absence or presence of M6P. Inhibition
      of Cat K processing by Rp-cAMP, KT5720 or H89 was observed in a dose-dependent
      manner. Furthermore, the addition of M6P resulted in enhanced potency of Rp-cAMP,
      KT5720 and H89, which dose-dependently inhibited in vitro bone resorption with
      potency similar to that observed for inhibition of Cat K processing.

PMID- 16644481
TI  - Differences of gene expression in bovine alveolar macrophages infected with
      virulent and attenuated isogenic strains of Mycobacterium bovis.
AB  - Infection with Mycobacterium bovis is a significant human and animal health
      problem in many parts of the world. The first stage of pulmonary tuberculosis
      occurs after inhalation of the bacilli into an alveolus where they are ingested
      by resident macrophages. DNA microarray analysis was used to detect genes
      expressed in bovine lung alveolar macrophages infected with two isogenic strains
      of M. bovis, a virulent strain, ATCC35723 and an attenuated strain, WAg520
      derived from ATCC35723. Chemokines, interleukin-8 and monocyte chemotactic
      protein 1, were more strongly expressed in ATCC35723-infected macrophages
      compared to WAg520-infected macrophages. Conversely, a group of genes, including
      fibrinogen-like protein 2 and legumain, were expressed at a higher level in
      macrophages infected with WAg520 compared to ATCC35723. Quantitative real-time
      PCR of a selected group of these differentially expressed genes confirmed
      enhanced levels of IL-8 mRNA in ATCC35723-infected macrophages compared to WAg520
      infected macrophages. Microarray analysis of gene expression in macrophages
      infected with attenuated isogenic strains of M. bovis may identify key genes
      involved in early and protective immune responses to tuberculosis.

PMID- 16644482
TI  - Expression of non-muscle myosin heavy chain in rat heart after immunosuppressive
      treatment.
AB  - Myosins constitute a large family of molecular motors, hydrolyzing ATP and
      producing cellular movement. To date, a large number of novel isoforms have been
      found in muscle and non-muscle cells. Among non-muscle myosins, non-muscle myosin
      heavy chain (NMHC) II-A and II-B have been well characterized. An additional
      member of NMHC II-B, with a molecular weight of 220 kDa, was recently identified
      in bovine skeletal muscle. NMHC II-B proteins, in particular, have been suggested
      to be a useful early molecular marker for the detection of pathological
      conditions during acute or chronic organ rejection in which fibrotic changes
      occur. Since it is known that treatment with cyclosporine A (CsA), an
      immunosuppressive drug successfully used for preventing organ rejection and
      autoimmune diseases, is often associated with several side effects (hypertension
      and nephrotoxicity), the aims of this study were: (1) to demonstrate the homology
      of the new NMHC protein (220 kDa) in other mammalian species, such as Wistar
      rats; (2) to evaluate, by morphological and immunohistochemical studies, the
      possible changes induced by CsA treatment in NMHC protein (220 kDa) cellular
      localization and/or in its expression levels in myocardial tissue. First of all,
      our results showed a greater homology of the new NMHC within the same isoforms
      across species and between isoforms in the same specie; moreover, we observed
      that this protein increased following CsA treatment. This could be explained as a
      tentative of cardiac tissue to maintain the structural integrity of intercalated
      disks and so the contraction/relaxation process.

PMID- 16644483
TI  - Safety and efficiency of an anti-(+)-methamphetamine monoclonal antibody in the
      protection against cardiovascular and central nervous system effects of (+)
      methamphetamine in rats.
AB  - The purpose of these studies was to determine if a high-affinity, anti-(+)
      methamphetamine (METH) monoclonal antibody (mAb6H4; KD=11 nM) protects against
      METH-induced central nervous and cardiovascular system effects in rats. Rats (n=5
      per group) received one of three anti-METH mAb6H4 doses, equal to 0.32, 0.56 or 1
      times the mole equivalent (mol-eq) amount of METH in the body following a 1 mg/kg
      i.v. METH dose. Each rat was challenged with METH (1 mg/kg, i.v.) 1 and 4 days
      after the anti-METH mAb dose. The 1 mol-eq anti-METH mAb dose significantly
      reduced the duration of METH-induced locomotor activity (horizontal locomotion
      and rearing events), heart rate and blood pressure effects from 2 to 3 h to about
      an hour. This resulted in a significant reduction in total locomotor activity and
      the area under the hemodynamic effect vs. time curve for heart rate and blood
      pressure. In addition, the time to peak locomotor activity was decreased after
      the 1 mol-eq mAb dose vs. the lower doses. These changes were limited to the
      first METH challenge. The responses to the second METH challenge were not
      different from baseline. The peak hemodynamic and locomotor activity values were
      unchanged after both challenges. These results indicate anti-METH mAb6H4 can
      safely reduce the hemodynamic and locomotor effects of METH given one day after
      anti-METH IgG, and that the mAb is safe when administered in the absence of METH.
      These results are important because they indicate these antibody medications have
      simultaneous beneficial effects in multiple organ systems.

PMID- 16644484
TI  - Suppressive effect of verproside isolated from Pseudolysimachion longifolium on
      airway inflammation in a mouse model of allergic asthma.
AB  - Allergic inflammation of the airways has a critical role in asthma development.
      We investigated a suppressive effect of verproside (3,4-dihydroxy catalpol)
      isolated from the extract of Pseudolysimachion longifolium on asthmatic
      parameters--such as immunoglobulin E (IgE) level, cytokine release, eosinophilia,
      airway hyperresponsiveness and mucus hypersecretion--in an OVA
      sensitized/challenged mouse model. Verproside significantly inhibited the
      increase of total IgE and the cytokines IL-4 and IL-13 in plasma and
      bronchoalveolar lavage fluid, and also effectively suppressed airway
      hyperresponsiveness, eosinophilia and mucus hypersecretion in OVA-induced
      asthmatic mice. The efficacy of verproside was comparable to montelukast, an anti
      asthmatic drug that is currently available. These results suggest that verproside
      could be a major marker in herbal medicines that are used for asthma treatment,
      and could also act as a lead for anti-asthmatic drugs.

PMID- 16644485
TI  - JNK inhibitor SP600125 reduces COX-2 expression by attenuating mRNA in activated
      murine J774 macrophages.
AB  - Inducible prostaglandin synthase (cyclooxygenase-2, COX-2) is highly expressed in
      inflammation. The signaling mechanisms involved in the up-regulation of COX-2 are
      not known in detail. In the present study we investigated the role of c-Jun NH2
      terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK)
      family in COX-2 expression and prostaglandin (PG) E2 production in murine J774
      macrophages activated by bacterial lipopolysaccharide (LPS). LPS caused a
      transient activation of JNK which was followed by increased COX-2 expression.
      Anthra(1,9-cd)pyrazol-6(2H)-one (SP600125), an inhibitor of JNK, inhibited
      phosphorylation of c-Jun with an IC50 of 5-10 microM. At the same concentrations
      SP600125 suppressed also LPS-induced COX-2 protein levels and PGE2 production.
      SP600125 did not alter LPS-induced COX-2 mRNA levels when measured 3 h after
      addition of LPS, whereas mRNA levels were significantly reduced in SP600125
      treated cells when measured 24 h after addition of LPS. LPS-induced COX-2 mRNA
      levels reduced faster in cells treated with SP600125 than in control cells.
      Cycloheximide (that is known to activate JNK) enhanced COX-2 expression and its
      effect was inhibited by SP600125. The present results suggest that JNK pathway is
      involved in the up-regulation of COX-2 expression possibly by a mechanism related
      to the stability of COX-2 mRNA.

PMID- 16644486
TI  - Expression and localisation of kinin receptors in colorectal polyps.
AB  - Kinins increase vascular permeability as well as mitogenesis and proliferation,
      hence they have a potential to promote neoplasmatic transformation. In the
      present study we investigated the expression profile and localization of kinin B1
      and B2 receptors in colorectal polyps. The biopsy samples from various polyps
      were obtained during endoscopy in tubular (n=18), villous (n=15) and hyperplasic
      polyps (n=15). The expression of genes encoding B1 and B2 was estimated by QRT
      PCR TaqMan analysis. In second series B1 and B2 receptors were visualized by
      immunohistochemical staining in tissue specimens from colonic polyps and adjacent
      normal tissue. We found the highest expression of gene encoding B1 in tubular
      adenomas (1891 number of copies mRNA/microg total RNA+/-312 SE) which is
      significantly higher as compared with controls (683+/-197 SE, p<0.013). In
      contrast, the expression of gene for B2 was significantly increased in
      hyperplastic polyps (3852+/-936 SE) as compared with controls (843+/-263 SE,
      p<0.0016). In normal colon a well as in hyperplasic polyps B1 and B2 receptors
      were immunohistochemically localized in enterocytes, however in hyperplastic
      polyps the intensity of staining was more prominent for B2 comparing to the
      control group. In contrast, in tubular adenomas staining reaction for B1 was more
      intense than in control samples. Increased level of B1 in adenoma suggests that
      kinins may play a role in abnormal cellular transformation; whereas higher B2
      level in hyperplasic polyp suggests its protective role. Our data may indicate
      that the overall effect of kinins on cellular proliferation depends on the
      relative level of B1 and B2 receptor expression.

PMID- 16644487
TI  - Xiao chai hu tang inhibits CVB1 virus infection of CCFS-1 cells through the
      induction of Type I interferon expression.
AB  - Coxsackie B virus type 1 (CVB1) infection is known to cause high morbidity and
      mortality in children, however, there is no effective drug for treating this
      disease. The present study aimed to examine the antiviral activity of xiao chai
      hu tang (XCHT), a popular herbal drug for treating viral and bacterial
      infections, against CVB1 infection and its mechanisms of action. Our data showed
      that XCHT neutralized the CVB1-induced cytopathic effect in human neonatal
      foreskin fibroblast cell line (CCFS-1/KMC), with IC50 (virus-induced cytopathic
      effect by 50%) and EC50 (concentration of 50% effectiveness) values around 12.39
      and 50.93 microg/ml, respectively. Its CC50 (concentration of 50% cellular
      cytotoxicity) and SI (selective index) values were 945.75 microg/ml and 18.92,
      respectively. These results suggest that XCHT possessed anti-CVB1 activity, and
      showed no effect on CCFS-1 cell viability and growth at concentration 250
      microg/ml. The time-of-addition studies showed that XCHT (50, 100 and 200
      microg/ml) added at various time of preinfection (-1 to -3 h), coinfection (0 h)
      and postinfection (1 approximately 3 h) could inhibit CVB1 infection.
      Interestingly, XCHT also showed an inhibition on viral replication through the
      induction of IFN-alpha/beta expression. In conclusion, XCHT possessed antiviral
      activity against CVB1 infection. It interfered the early stage of viral
      replication (prophylactic effect) and viral replication after infection
      (therapeutic effect) through the induction of Type I interferon expression.

PMID- 16644488
TI  - Reduction of lipopolysaccharide-induced interleukin-6 production by the kappa
      opioid U50,488 in a mouse monocyte-like cell line.
AB  - Several studies demonstrate that opioids modulate the immune response via opioid
      receptors expressed directly on the immune cells themselves. Recently, it has
      been suggested that the kappa opioid system has a modulatory role in various
      inflammatory diseases including rheumatoid arthritis. This modulation may occur
      via changes in cytokine secretion by monocyte-derived cells. To further study
      this opioid-immune relationship, we stimulated P388D1 cells, a mouse monocyte
      like cell line, with lipopolysaccharide (LPS) in the presence or absence of the
      kappa opioid-selective ligand, U50,488. Pretreatment with U50,488 significantly
      reduced LPS-stimulated interleukin-6 (IL-6) production as measured by ELISA. This
      effect was mediated by the kappa opioid receptor, because nor-binaltorphimine
      (nor-BNI), a kappa-selective antagonist, blocked this inhibition. It is likely
      that this reduction of IL-6 protein by U50,488 treatment is attributed to
      decreases in IL-6 mRNA. RT-PCR experiments demonstrated that U50,488 treatment
      significantly reduced the LPS-mediated increase in IL-6 mRNA and that this effect
      was also blocked by nor-BNI. Understanding the mechanism behind the reduction of
      proinflammatory cytokine production by opioids may lead to the development of
      more effective therapeutics for inflammatory diseases.

PMID- 16644489
TI  - Human NK cell IFN-gamma production is regulated by endogenous TGF-beta.
AB  - NK cells are an important component of innate immunity, and they can promote CTL
      and Th1 cell development and macrophage activation via cytokines. TGF-beta is
      believed to be an important immunoregulatory molecule, and for this reason
      several TGF-beta inhibitors are currently in clinical development. However, the
      modulation of specific innate immune responses by endogenous human TGF-beta
      remains unclear. In this study, we demonstrate that blocking the action of
      endogenous TGF-beta resulted in an increase in both the percentage of responding
      NK cells and the amount of IFN-gamma produced by human NK cells when stimulated
      by monokines and TLR agonists. Blocking endogenous TGF-beta resulted in
      significant NK cell IFN-gamma production under suboptimal stimulation conditions.
      Our findings also suggest that TGF-beta associated with other blood cells may be
      involved in limiting NK cell activation. Thus, inhibiting endogenous TGF-beta
      provides a means to shift NK cell activation and promote cellular immunity.

PMID- 16644490
TI  - Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and
      transforming growth factor-beta1.
AB  - The neuropharmacological properties of cocaine are known to be associated with
      the activation of sigma-1 receptors. Cocaine also has been shown to alter both
      cytokine production and HIV-1 expression in mononuclear phagocytes, including
      microglial cells. This study tested the hypothesis that sigma-1 receptors and
      transforming growth factor (TGF)-beta1 are involved in cocaine-induced up
      regulation of HIV-1 expression in microglial cell cultures. Treatment of
      microglial cells with cocaine resulted in a concentration-dependent increase in
      viral expression assessed by measurement of p24 antigen levels in culture
      supernatants. This cocaine-mediated stimulation of HIV-1 expression was blocked
      by treatment of microglia with inhibitors of sigma-1 receptors (BD1047) and TGF
      beta1 (SB-431542 and anti-TGF-beta1 antibodies). Microglia were also shown to
      constitutively express sigma-1 receptor mRNA. Thus, the results of this study
      support the notion that neuroimmunopharmacological properties of cocaine involve
      sigma-1 receptors and cytokines.

PMID- 16644491
TI  - IL-2 increased RANTES production and CD25 expression in cultured PBMCs only from
      antiretroviral treated HIV-1+ patients with detectable viral loads.
AB  - In order to better understand the possible beneficial effects of intermittent IL
      2 treatment as complement of antiretroviral therapy in HIV-1+ patients, we have
      measured the levels of RANTES in the supernatants and the CD25 expression in
      cultured PBMCs obtained from HIV-1+ individuals in presence of IL-2. The results
      showed a significant increases in RANTES production and in the expression of
      CD25+ in the cultures with IL-2 of PBMC obtained from HIV-1+ patients with a
      detectable viral load in comparison with both, HIV-1+ patients with no detectable
      viral loads and with healthy individuals. These results suggest that therapeutic
      IL-2 administered in addition to highly active anti-retroviral therapy (HAART)
      may contribute to increase the effect of this therapy by rising both RANTES
      production and CD25 expression only in HIV-1+ patients with detectable viral
      loads.

PMID- 16644492
TI  - [Monoclonal antibodies: technology around the clock for new therapeutic hopes].
AB  - Engineering monoclonal antibodies, now widely used in the clinic, has made it
      possible to develop a new generation of antibodies with optimized functional
      properties. These antibodies should allow a significant improvement of the
      treatment of diseases where only few drugs are available, if any. However, the
      cost of treatments with monoclonal antibodies requires further improvements in
      production and purification technologies, and raises the question of generic
      antibodies. The present review summarizes some of the technological past and
      present challenges in the field.

PMID- 16644493
TI  - [Monoclonal antibodies in the treatment of rheumatoid arthritis: toward a
      therapeutic revolution].
AB  - The progress of immunopathology allowed the development of targeted drugs or
      biotherapies. Among them, monoclonal antibodies against T or B lymphocytes or
      against a cytokine are reported. Monoclonal anti-TNF antibodies are a major
      therapeutic advance because they can stop the clinical, biological and
      radiographic evolution of rheumatoid arthritis (RA). Monoclonal anti-CD20
      lymphocytes give promising results; they are able to induce prolonged remissions.
      Monoclonal anti-IL6 receptors are currently being evaluated. They are efficacious
      in adult RA and in Still's disease. Because of the infectious risk linked to
      these drugs, the ratio benefit/risk must be carefully evaluated before the
      prescription of a biotherapy.

PMID- 16644494
TI  - Monoclonal antibody as therapy for malignant lymphomas.
AB  - Rituximab was the first monoclonal antibody to have been registered for the
      treatment of B-cell lymphomas. Randomized studies have demonstrated its activity
      in follicular lymphoma, mantle-cell lymphoma, and diffuse large B-cell lymphoma
      in untreated or relapsing patients. Because of its high activity and low toxicity
      ratio, rituximab has transformed the outcome of patients with B-cell lymphoma. A
      combination of rituximab plus chemotherapy, R-CHOP, has the highest efficacy ever
      described with any chemotherapy in diffuse large B-cell lymphoma and follicular
      lymphoma. The role of radio-labelled antibodies is still to be defined.

PMID- 16644495
TI  - Principles of the therapeutic use of monoclonal antibodies in oncology.
AB  - Monoclonal antibodies have reached the stage of therapeutic agents, mostly in
      oncology, as illustrated by their wide use in lymphoma, breast cancer or
      colorectal cancer. The unravelling of their mechanisms of action and their
      interactions with their cellular receptors allows us to engineer new classes of
      therapeutic antibodies with increased efficacy. The identification of some of the
      tumour escape mechanisms may also help to define new approaches for patient
      selection and immunomonitoring. The present review addresses these various
      aspects.

PMID- 16644496
TI  - Induction of immunological tolerance using monoclonal antibodies: applications to
      organ transplantation and autoimmune disease.
AB  - Immunologic tolerance is a state of immune paralysis specific to a given antigen
      (the tolerogen) coexisting with the maintenance of normal immunocompetence
      towards other antigens. Anti-T cell monoclonal antibodies allow its induction in
      organ transplantation and autoimmune disease essentially through the stimulation
      of regulatory T cells. Very promising results obtained in animals have been
      recently confirmed in the human in recent-onset insulin-dependent diabetes
      mellitus with an anti-CD3 antibody (with long-term remission of the disease
      following a treatment of only six days).

PMID- 16644497
TI  - [Use of monoclonal antibodies in therapeutics. Conclusion].

PMID- 16644498
TI  - Highlighting ontogenetic shifts in habitat use by nocturnal coral reef fish.
AB  - The lagoon of Moorea Island was characterised by 12 distinct reef zones. Visual
      censuses allowed us to document the spatial distributions of recently settled
      juveniles vs adults of 17 nocturnal fish species among the 12 reef zones. Five
      distinct patterns in habitat use were found: an increase in the number of reef
      zones used during the adult stage (four species); a decrease in the number of
      reef zones adults used compared to recently settled juveniles (two species); the
      use of different reef zones (one species); the use of same reef zones but with
      relative densities different (one species); and no change in habitat use (nine
      species). Overall, this study is the first to explore the use of space by a broad
      range of nocturnal fish taxa to document the patterns and determinism of habitat
      shifts between juvenile and adult life stages.

PMID- 16644499
TI  - Phospholipid changes in seqA and dam mutants of Escherichia coli.
AB  - SeqA and Dam proteins were known to be responsible for regulating the initiation
      of replication and to affect the expression of many genes and metabolisms. We
      have examined here the fatty acids composition and phospholipids membrane in dam
      and/or seqA mutants. The dam mutant showed an accumulation of the acidic
      phospholipids cardiolipin, whereas, the seqA mutant showed a higher proportion of
      phosphatidylglycerol compared with the wild-type strain. The seqA dam double
      mutant showed an intermediate proportion of acidic phospholipids compared with
      the wild-type strain. Based on these observations, we discuss the role of Dam and
      SeqA proteins in the regulation of phospholipids synthesis.

PMID- 16644500
TI  - Marine mammal strandings in the New Caledonia region, Southwest Pacific.
AB  - Four hundred twenty three marine mammals, in 72 stranding events, were recorded
      between 1877 and 2005 in New Caledonia, the Loyalty Islands, and Vanuatu in the
      southwest Pacific. Sixteen species were represented in this count, including:
      minke whale, Balaenoptera acutorostrata (1 single stranding), sei whale, B.
      borealis (1 single stranding), blue whale, B. musculus (1 single stranding),
      humpback whale, Megaptera novaeangliae (2 single strandings), giant sperm whale,
      Physeter macrocephalus (18 single strandings, 2 pair strandings), pygmy sperm
      whale, Kogia breviceps (5 single strandings), dwarf sperm whale, K. sima (2
      single strandings, 1 triple stranding), Blainville's beaked whale, Mesoplodon
      densirostris (2 single strandings), short-finned pilot whale, Globicephala
      macrorhynchus (4 strandings, 56 individuals), melon-headed whale, Peponocephala
      electra (1 single stranding and 2 mass strandings totalling 231 individuals),
      common dolphin, Delphinus delphis (1 single stranding), spinner dolphin, Stenella
      longirostris (1 pair stranding and 2 mass strandings of groups of approximately
      30 individuals each), Indian Ocean bottlenose dolphin, Tursiops aduncus (2 single
      strandings), dugong, Dugong dugon (14 single strandings), and New Zealand fur
      seal, Arctocephalus forsteri (3 single strandings). A stranded rorqual identified
      as an Antarctic minke whale (B. bonaerensis), with coloration patterns that did
      not match known descriptions, was also reported. Sei whale was recorded for the
      first time in the tropical Southwest Pacific region and Antarctic minke whale,
      melon-headed whale, and Indian Ocean bottlenose dolphin were recorded for the
      first time in New Caledonia. Strandings of sperm whales were most frequent in the
      spring, but also occurred in autumn months, suggesting a seasonal pattern of
      occurrence possibly related to seasonal migration. One stranded humpback whale
      bore the scars of a killer whale's attack and one dugong was injured by a shark.
      Scars left by propellers were noted on several stranded animals including one
      Antarctic minke whale, one pygmy sperm whale, one dwarf sperm whale, and four
      dugongs. Collisions with vessels were suspected to be a frequent cause of death
      for dugong.

PMID- 16644501
TI  - Mountain scorpions: a new genus and species from Tibet (China).
AB  - A new genus and species of mountain liochelid scorpion are described on the basis
      of a single specimen collected in Tibet (China). This is the first liochelid
      scorpion found in the high Himalayan Mountains of Tibet, and the first example of
      the family to be collected out of its typical tropical and subtropical areas of
      distribution. Some considerations on mountain scorpions are proposed.

PMID- 16644502
TI  - Prognostic value of angiogenesis evaluated with high-frequency and colour Doppler
      sonography for preoperative assessment of primary cutaneous melanomas:
      correlation with recurrence after a 5 year follow-up period.
AB  - OBJECTIVE: To study the value of high-frequency sonography (HFS) and colour
      Doppler sonography (CDS) in evaluating the 5 year metastatic potential of primary
      cutaneous melanomas (CM). MATERIALS AND METHODS: 111 CM were studied before
      surgical resection and 107 were depicted on HFS. The maximal HFS thickness was
      measured and compared with the Breslow thickness. A CDS study was performed in
      each tumour. RESULTS: HFS thickness ranged from 0.26 to 8.0 mm and Breslow
      thickness from 0.15 to 8.0 mm. HFS and Breslow thickness correlated strongly (r >
      0.93). Intratumour vessels were depicted in 43 of the 107 CM, of which 40 were
      thicker than 2 mm. The median follow-up was 61 months and 27 patients developed
      relapses. In the univariate analyses, neovascularization visualized with CDS,
      sonographic thickness and the Breslow thickness were significantly linked to
      relapses (p < 0.0001), as were lymph node status and ulceration (p = 0.007 and
      0.004). CONCLUSION: Vascularization was observed mainly in thick primary
      melanoma. A median follow-up of 5 years showed the prognostic value of
      angiogenesis evaluated by CDS.

PMID- 16644503
TI  - Defining the radiation target on a daily basis.
AB  - The delineation of the target volume for irradiation is a critical step in the
      radiotherapy process. Delivery of radiotherapy occurs over a fractionated course
      of many treatments. Variations in the position of the target volume may occur on
      a daily basis during treatment and so the procedure for defining the target
      volume on a single initial 'snapshot' computed tomography scan has been re
      evaluated. Newer technologies of image-guided radiotherapy allow the development
      of on-line daily definition of the target volume prior to radiotherapy delivery.

PMID- 16644504
TI  - Medical advances from science and engineering.

PMID- 16644505
TI  - Randomized controlled trial to determine the effectiveness of the Nivatvongs
      technique versus conventional local anaesthetic infiltration for outpatient
      haemorrhoidectomy.
AB  - BACKGROUND: Conventional local anaesthesia in outpatient haemorrhoidectomy, using
      a diamond-shaped perianal block, is reliable, safe and inexpensive. It allows for
      early ambulation and short hospital stay. However, without sedation, local
      infiltration is perceived to be both uncomfortable and painful. Nivatvongs
      described a technique in which the anaesthetic is injected intra-anally into the
      insensitive area above the dentate line, allegedly causing less pain. METHODS:
      This randomized, controlled, parallel-group, single-blind clinical trial compared
      the effectiveness of the conventional and Nivatvongs techniques in reducing the
      pain of anaesthetic infiltration in adult patients undergoing outpatient
      haemorrhoidectomy. A total of 112 patients were randomized into either treatment
      (n=57) or control groups (n=55). Assigned surgeon-anaesthetists performed the
      local anaesthetic infiltration. The Milligan-Morgan technique was used for
      haemorrhoidectomy. Pain was assessed using a standardized visual analogue scale.
      Patient and surgeon satisfaction were measured with a pre-validated
      questionnaire. RESULTS: Median scores for pain assessment during local
      anaesthetic infiltration were 2 and 3 in the control and treatment groups,
      respectively. Patient satisfaction with the method of anaesthetic infiltration
      and the procedure itself were 3 and 2, respectively, for both groups. The
      surgeon's overall satisfaction with the technique of anaesthetic infiltration was
      similar in the two groups. There was no significant difference in any of the
      outcomes measured. CONCLUSION: Both local anaesthetic techniques for outpatient
      haemorrhoidectomy were generally effective and well tolerated. The Nivatvongs
      technique did not confer any significant additional benefit.

PMID- 16644506
TI  - Comparative study of tailor-made mesh plug herniorrhaphy versus Lichtenstein
      herniorrhaphy versus Bassini operation: a prospective clinical trial.
AB  - OBJECTIVE: Operations to cure inguinal hernia are among the most common surgical
      procedures. However, the most effective surgical technique for inguinal hernia
      repair is unknown, and the recurrence at 5 years varies between 1% and 10%.
      Surgical techniques and implanted materials are crucial to the result of and
      costs associated with hernia repair. The objective of this study was to determine
      whether the tailor-made mesh plug for inguinal hernia repair was as effective and
      safe as other methods of herniorrhaphy. METHODS: Of 94 patients who had a primary
      diagnosis of inguinal hernia prospectively included in the study, 25 were treated
      with tailor-made mesh plug herniorrhaphy, 26 with Lichtenstein herniorrhaphy and
      36 with the Bassini operation. The primary outcome was the recurrence of hernia
      at 1 year, and secondary outcomes included surgical complications and hospital
      stay. RESULTS: There was no postoperative mortality in this study. Three patients
      had recurrence after Bassini operation, but there was no recurrent hernia after
      Lichtenstein or mesh plug herniorrhaphy. Groin swelling and ecchymosis were found
      in two patients (1 tailor-made mesh plug, 1 Lichtenstein herniorrhaphy). No
      surgical site infection occurred. Mean operating time was 60 minutes (range, 45
      75 minutes) for tailor-made mesh plug herniorrhaphy, 82 minutes (range, 30-120
      minutes) for Lichtenstein herniorrhaphy, and 82 minutes (range, 30-135 minutes)
      for the Bassini operation. CONCLUSION: Tailor-made mesh plug herniorrhaphy is a
      safe operation. The mesh plug material (Mersilene) was cheap. The recurrence rate
      was lower with tailor-made mesh plug herniorrhaphy than with the Bassini
      operation, but equal to that with Lichtenstein herniorrhaphy. Postoperative
      complications did not differ among all operations.

PMID- 16644507
TI  - Effect of four crystalloid cardioplegias on immature rabbit hearts during global
      ischaemia.
AB  - OBJECTIVE: Controversy surrounds the reported beneficial effects of crystalloid
      cardioplegic solutions in the immature myocardium. In the present study, we
      investigated the efficacy of four clinical cardioplegic solutions in the immature
      myocardium to determine if cardioplegic protection could be demonstrated and, if
      yes, the relative efficacy of the four solutions. METHODS: Isolated, working
      hearts (n=6 per group) from neonatal rabbits (age, 7-14 days) were perfused
      aerobically (37 C) for 15 minutes in the Langendorff mode and 30 minutes in the
      working mode before a 2-minute infusion of one of four cardioplegic solutions:
      the modified St. Thomas' Hospital no. 1 cardioplegic solution, Tyers solution,
      Bretschneider solution or Roe solution. Hearts were then rendered globally
      ischaemic for 120 minutes at 14C before reperfusion for 15 minutes in the
      Langendorff mode and 30 minutes in the working mode. The post-ischaemic recovery
      of cardiac function and leakage of myocardial enzymes (GOT, CK, CK-MB, LDH, LDH1)
      were compared with results in non-cardioplegic control hearts. RESULTS: Good
      protection was observed with modified St. Thomas' Hospital and Tyers solutions:
      postischaemic recovery of cardiac output was increased from 80.43+/-3.62% in the
      non-cardioplegic group to 85.19+/-3.12% and 70.66+/-3.48% in the St. Thomas'
      Hospital and Tyers groups (p<0.05), respectively. In contrast, no obvious
      protection was observed with either the Bretschneider or Roe solutions: cardiac
      output recovered to 45.08+/-3.16% and 30.06+/-2.59%, respectively. Post-ischaemic
      CK leakage was 19.83+/-2.14 IU/mL and 21.17+/-2.32 IU/mL in the St. Thomas'
      Hospital and Tyers groups (p>0.05). In the Bretschneider group, CK leakage
      increased to 30.00+/-3.16 IU/mL (p<0.01 vs. non-cardioplegic control hearts), and
      in the Roe group, CK leakage was 31.00+/-5.10 IU/mL (p<0.05 vs. cardioplegic-free
      hearts). Post-ischaemic ATP was 1.98+/-0.54 micromol/g*dry weight and 1.35+/-0.39
      micromol/g*dry weight in the St. Thomas' Hospital and Tyers groups (p<0.01 vs.
      non-cardioplegic control group), respectively. In the Bretschneider group, ATP
      decreased to 0.91+/-0.16 micromol/g*dry weight (p<0.05 vs. non-cardioplegic
      control hearts), and in the Roe group to 0.88+/-0.10 micromol/g*dry weight
      (p<0.01 vs.cardioplegic-free hearts). CONCLUSION: In conclusion, cardioplegic
      protection can be achieved in the immature rabbit myocardium with both St.
      Thomas' Hospital and Tyers solutions, but acalcaemic solutions such as
      Bretschneider and Roe solutions increased damage. The reported lack of
      cardioplegic efficacy in the immature myocardium may, therefore, reflect the
      choice of cardioplegic solution rather than a greater vulnerability to injury in
      the neonatal heart.

PMID- 16644508
TI  - Pulmonary embolism: a frequent occurrence in Indian patients with symptomatic
      lower limb venous thrombosis.
AB  - OBJECTIVE: Pulmonary embolism (PE) is the most severe complication of deep venous
      thrombosis (DVT). There have been very few studies to assess the prevalence of PE
      in Asian patients. The objective of this study was to define the prevalence of PE
      in patients presenting with suspected lower limb DVT. METHODS: This was a
      prospective cohort study at Sir Ganga Ram Hospital, a large multispecialty
      hospital in New Delhi, India. From January 2001 to July 2004, 1,552 consecutive
      inpatients and outpatients who presented with clinically suspected lower limb DVT
      were enrolled in the study. Combined ascending radionuclide venography and lung
      perfusion scan was performed in all patients. Patients with evidence of pulmonary
      perfusion defects underwent ventilation lung scan. RESULTS: Radionuclide
      venography-detectable DVT was noted in 744 patients, of whom 521 (70%) had
      suprapopliteal DVT. Of patients with DVT, 294 (39.5%) showed a high-probability
      lung scan and 135 (18.1%) had an intermediate-probability lung scan. Overall, 47%
      of patients with a high-probability scan had no clinical manifestations
      suggestive of PE. CONCLUSION: PE occurs frequently in Indian patients with
      symptomatic DVT. Increasing awareness will provide us with clearer ideas about
      the prevalence of venous thromboembolism in Asian countries.

PMID- 16644509
TI  - Contrast CT in localization of acute lower gastrointestinal bleeding.
AB  - Localization of the source of acute lower gastrointestinal bleeding is of
      paramount importance in its management as it allows for planned segmental
      resection rather than a "blind" abdominal total colectomy. Various methods of
      localization with radionuclide scan, mesenteric angiography and colonoscopy have
      been utilized, but none has been shown to be superior to others. The recent use
      of contrast-enhanced multislice computed tomography (MSCT) has generated much
      interest as it is rapid, noninvasive and readily accessible, and allows for
      excellent reformation on different planes. These are clear advantages in an
      emergency setting for accurate localization prior to surgery. We report a case
      where the use of MSCT resulted in prompt and accurate localization in a patient
      who presented acutely with massive lower gastrointestinal bleed. We believe that
      contrast-enhanced MSCT has the potential of accurately localizing the source of
      bleeding in an emergency setting, and should be part of the algorithm in the
      management of acute lower gastrointestinal bleeding.

PMID- 16644510
TI  - Mucinous adenocarcinoma of the rectum with breast and ocular metastases.
AB  - We present the case of a 32-year-old woman who, 10 months after abdominoperineal
      resection and total mesorectal excision for a locally advanced mucinous
      adenocarcinoma of the rectum, presented with local recurrence and metastases to
      the breast, spine, the left eye and orbit. Following surgery, due to the
      patient's personal reasons, adjuvant chemoradiation was not given. The patient
      died 2 months later, with disseminated cancer. To the best of our knowledge,
      breast as well as ocular metastasis in a patient with mucinous adenocarcinoma of
      the rectum has never been reported and, therefore, needs to be documented.

PMID- 16644511
TI  - Massive dissecting intramural duodenal haematoma following endoscopic haemostasis
      of a bleeding duodenal ulcer.
AB  - Intramural duodenal haematoma is a rare injury of the duodenum. Most reported
      cases are secondary to blunt trauma to the abdomen. Such injury following
      endoscopic intervention is even rarer, and there are no definite guidelines for
      its management. We report a case where endoscopic haemostasis of a bleeding
      duodenal ulcer resulted in a massive dissecting intramural duodenal haematoma
      with gastric outlet obstruction and obstructive jaundice.

PMID- 16644512
TI  - Forehead flap method for total nasal reconstruction.
AB  - One of the very first recorded methods developed over the ages to correct the
      mutilating deformity of rhinectomy was the forehead flap. While many other
      techniques have also been devised, this surgical method has stood the test of
      time better than any other. Further refined during the 20th century, it has now
      become the gold standard for obtaining the best results in nasal reconstruction.
      We present an illustrative case of a young man who was assaulted outside a night
      club and who suffered a clean separation of the nasal pyramid from the facial
      plane. We highlight the novel use of osseous, as opposed to cartilaginous,
      reconstruction of the upper lateral cartilages, which has not previously been
      reported in the literature.

PMID- 16644513
TI  - Spectrum of features in pterygium syndrome.
AB  - Pterygium syndrome is a complex and rare congenital deformity that consists of
      contractures involving multiple flexural surfaces and associated craniofacial
      anomalies. It often has associated conditions, including anomalies of the
      cardiovascular, respiratory, gastrointestinal and genitourinary systems. It may
      present in different forms, including multiple pterygium syndrome of Escobar,
      lethal multiple pterygium syndrome, popliteal pterygium syndrome, lethal
      popliteal syndrome (Bartsocas-Papas syndrome) and arthrogryposis multiplex
      congenita. The clinical presentation, multidisciplinary management and the long
      term outcome in three patients with this condition are presented.

PMID- 16644514
TI  - Bilateral congenital dacryocystocoeles with concurrent intranasal mucocoeles
      causing respiratory distress in a neonate.
AB  - Congenital dacryocystocoeles are uncommon, presenting as a fluctuant bluish mass
      inferior to the medial canthus. Even more rarely, these dacryocystocoeles are
      complicated by intranasal extension. We present a case of a newborn infant with
      bilateral dacryocystocoeles with intranasal extension (intranasal mucocoeles)
      causing respiratory distress and feeding difficulties. Prompt surgical correction
      was performed, with the mucocoeles being de-roofed, leading to the resolution of
      the dacryocystocoeles. The aetiology, clinical features, and therapeutic options
      are discussed.

PMID- 16644515
TI  - Middle-finger reflex.
AB  - A new reflex is described: middle-finger extensor reflex elicited by percussion
      of tendon insertion of musculus extensor digitorum communis in forearm. Following
      percussion using a reflex hammer, two EMG responses from the belly of the muscle
      were recorded: a short latency monosynaptic reflex with a latency of 31.4 +/- 1.5
      ms (M1), and a long-latency middle-finger reflex with a mean latency of 64.8 +/-
      6.31 ms (M2), the former being a monosynaptic extensor reflex, and the latter
      belonging to a spino-cortico-spinal reflex circuitry. It was suggested that the
      middle-finger extensor reflex elicited by radial nerve afferents and efferents
      (C7-C8) would be of clinical and theoretical importance.

PMID- 16644516
TI  - Disparity for disinhibitory and excitatory effects during cortical
      reorganization.
AB  - Inhibitory and excitatory transmission have been shown to be two dominant forces
      in the process of injury-induced cortical reorganization. However, the
      contributions of each individual neurotransmitter system have been difficult to
      characterize, mainly because they often affect overlapping domains of the
      reorganizing cell's receptive field (RF). The present work differentiates the
      effects of either neurotransmitter system by studying reorganizing neurons where
      pharmacological intervention directed at glutamatergic or GABAergic networks
      affected spatially non-overlapping subfields within a cell's RF.
      Microiontophoresis was used to apply glutamate and bicuculline, a selective GABA
      A receptor antagonist, to cells in the deafferented cortex at various post
      amputation times, that ranged from 2 to 37 weeks. It was found that at all post
      amputation times studied, glutamate increased the neural activity that could be
      evoked from mechanical stimulation over the wound area, in addition to decreasing
      the threshold for activation. Disinhibition with bicuculline application often
      lowered the response threshold for subfields within the reorganized RF, usually
      located on the digits, and could also expand RF area. Interestingly, the effects
      of GABAergic transmission to the process of reorganization appeared later than
      those mediated through glutamatergic networks. These findings suggest that
      recruitment of inhibition in reorganizing cells relies on activity-dependent
      mechanisms, with reinstatement of GABAergic transmission being secondary to the
      formation of novel glutamatergic drives.

PMID- 16644517
TI  - GAA repeat polymorphism in Turkish Friedreich's ataxia patients.
AB  - Friedreich's ataxia (FRDA), the most common subtype of early onset hereditary
      spinocerebellar ataxia (SCA), is an autosomal recessive neurodegenerative
      disorder caused by unstable GAA tri-nucleotide expansions in the first intron of
      FRDA gene located at 9q13-q21.1 position. Results of GAA repeat polymorphism in
      80 Turkish SCA patients and 38 family members of 11 typical FRDA patients were
      reported. GAA triplet repeat size ranged from approximately 7 to 34 in normal
      alleles and from approximately 66 to 1300 in mutant alleles. Twenty six patients
      were homozygous for GAA expansion and size of expanded alleles differed from
      approximately 425 to 1300 repeats. Children 2 and 6 years old (showing no ataxia
      symptoms) of one family had homozygous GAA expansions reaching approximately 925
      repeats. All 11 families studied had at least 1 afflicted child and 9 parents and
      2 siblings were carrier (heterozygous) with mutant alleles ranging from 66 to 850
      repeats. Family studies confirmed the meiotic instability and stronger effect of
      expansion in the smaller alleles on phenotype and a negative correlation between
      GAA repeat expansion size and onset-age of the disease.

PMID- 16644518
TI  - Increases in COX II mRNA in the rat spinal cord induced by cauda equina traction.
AB  - This article investigated the time response of COX II induction by traction of
      the cauda equina assessed by a quantified RT-PCR method. Under deep GOI
      anesthesia, male Wistar rats were fixed in the prone position and a laminectomy
      of the dorsal part of the first and second sacral vertebrae was performed.
      Following, COX II-mRNA levels in the cervical, thoracic, lumbar, sacral, and
      caudal segments were measured at 2, 4, 6, and 24 h after traction by a quantified
      RT-PCR method. After cauda equina traction, significant levels of COX II mRNA
      were detected in all segments of the spinal cord examined. Maximum levels in each
      segment were determined 4 h after traction of the cauda equina. Particularly in
      the sacrocaudal segments significantly higher levels of COX II mRNA were measured
      24 h after traction. These results indicate that significant induction of spinal
      COX II mRNA was caused by cauda equina traction and that such induction plays a
      regulatory role in the nociceptive pain pathway.

PMID- 16644519
TI  - Kainic acid activates oxytocinergic neurons through non-nmda glutamate receptors.
AB  - The present study assessed if kainic acid activates oxytocinergic neurons and
      this activation is blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Dual
      immunohistochemistry for oxytocin and c-Fos showed that oxytocin neurons in SON
      and PVN express c-Fos following kainic acid administration, a significant
      increase when compared to the control group. Administration of CNQX prior to
      kainic acid caused a significant reduction. The results suggested the
      participation of non-NMDA receptors in the regulation of oxytocin neurons because
      the administration of kainic acid activates these neurons and this activation is
      blocked by CNQX administration.

PMID- 16644520
TI  - Effects of valsartan on stress-induced changes of serum vascular endothelial
      growth factor and nitric oxide in mice.
AB  - This study investigated the effects of renin-angiotensin system (RAS) blockade on
      stress-induced changes of serum vascular endothelial growth factor (VEGF) and
      nitric oxide (NO) in mice. Chronic stress increased the serum NO levels
      significantly compared to control group (p = .0172). Valsartan, an angiotensin II
      receptor antagonist, alone, did not make significant difference versus control
      group. In chronic stress + valsartan group, serum NO levels decreased
      nonsignificantly compared to chronic stress group. There was a nonsignificant
      increase in serum VEGF levels after chronic stress. Valsartan alone or with
      chronic stress did not significantly affect the serum VEGF levels. In conclusion,
      there was no correlation between NO and VEGF changes during the stress response.
      In this respect, there may be other mechanisms to explain the stress-induced NO
      increase.

PMID- 16644521
TI  - The clinical utility of the Mattis Dementia Rating Scale in assessing cognitive
      decline in Alzheimer's disease.
AB  - The progression of cognitive decline in Alzheimer's disease (AD) was studied by
      examining patterns of test performance on successive administrations of the
      Mattis Dementia Rating Scale (DRS) in a sample of 63 participants who were
      diagnosed with probable AD. Assessments were performed at intervals ranging
      approximately from 3 to 38 months apart. Results indicated that the pattern of
      progression and sequence of neuropsychological decline in AD is influenced by sex
      and age of disease onset. Results offered support for the clinical staging of AD
      and further substantiated the clinical utility of the Mattis Dementia Rating
      Scale in staging degree of dementia.

PMID- 16644522
TI  - Polyneuropathies in the elderly: a clinico pathological study of 74 cases.
AB  - In elderly patients, peripheral neuropathies are common and may lead to
      disability. In order to investigate the relative incidence of different
      polyneuropathies in the elderly focusing on the contribution of nerve biopsy to
      their diagnosis, the authors studied 74 patients over 65 years of age with
      clinical, laboratory, electrophysiological, and sural nerve biopsy findings of
      different types of polyneuropathy. Vasculitic polyneuropathy seemed to be the
      most common cause of disabling neuropathy in the elderly, followed by
      paraneoplasia and diabetes. The possible diagnosis of idiopathic axonal
      neuropathy in the nine cases with neuropathy of unknown origin is discussed.

PMID- 16644523
TI  - Motor-evoked potentials following imagery and limb disuse.
AB  - This article investigated whether mental imagery training could reduce the
      detrimental effects produced by limb disuse. Subjects learned a task requiring
      fifth finger abduction. Motor-evoked potentials (MEPs) were obtained from the
      abductor digiti minimi muscle using transcranial magnetic stimulation. The arm
      was casted and the experimental group then practiced using imagery. After seven
      days, variable error scores increased. The immobilization treatment decreased MEP
      scores in both groups, with no difference between groups. It is concluded that
      limb immobilization produces a decrement in the area of motor cortex dedicated to
      this muscle as a result of disuse. Imagery failed to ameliorate the disuse
      related changes.

PMID- 16644524
TI  - Dysexecutive agraphia: a major executive dysfunction sign.
AB  - Different types of writing disorders associated with brain pathology have been
      described. Limited mention the writing disturbances associated with prefrontal
      pathology, however, is found. Clinical observations of patients not only with
      focal prefrontal pathology but also with other conditions affecting the frontal
      system (e.g., traumatic head injury, dementia) confirm the assumption that these
      patients present an overt decrease in the ability to express ideas in writing. It
      is proposed that complex aspects of writing, such as planning, narrative
      coherence, and maintained attention, are significantly disturbed in cases of
      impairments of executive functions. Frontal lobe patients not only have
      difficulties in keeping the effort required for writing, but also to organize the
      ideas in the written texts. The term dysexecutive agraphia is proposed to refer
      to this writing disorder. Three illustrative cases are presented. It is finally
      suggested that questions regarding the ability to write should be included in
      dementia questionnaires and executive functioning testing.

PMID- 16644525
TI  - Chemical constituents of the Vietnamese inedible mushroom Xylaria intracolorata.
AB  - Investigation of the methanolic extract of Vietnamese inedible Xylariaceous
      mushroom Xylaria intracolorata resulted in the isolation of two new compounds
      named coloratin A [3,5-dimethoxy-2-(6-oxo-5-pentyl-6H-pyran-3-carbonyl)-benzoic
      acid] (1) and coloratin B (2-carbomethoxyl-3,5-dimethoxybenzoic acid) (2). Their
      structures were elucidated by 2D-NMR, MS, IR, and UV spectroscopy. Coloratin A
      (1) showed strong antimicrobial activity.

PMID- 16644526
TI  - Antimicrobial potentiality of Phyllanthus amarus against drug resistant
      pathogens.
AB  - The antimicrobial potentiality of the methanolic extract of Phyllanthus amarus
      (Family: Euphorbiaceae) was studied against some drug resistant pathogenic
      bacterial strains by disc diffusion and agar dilution method. The extract showed
      significant concentration-dependent antibacterial activity particularly against
      gram-negative microbes. The study illustrated the claim of the usefulness of the
      plant in dysenteric and diarrheal infections and also suggested its use in fever.
      The antibacterial action was mainly due to the isolated phyllanthin.

PMID- 16644527
TI  - Potential cancer chemopreventive agents from Arbutus unedo.
AB  - A phytochemical study of the petroleum ether and ethyl acetate extracts of the
      entire plant of Arbutus unedo led to the isolation of a new sterol, 7beta
      hydroxystigmast-4-en-3-one (1), and nine known compounds of the flavan, steroid,
      and terpenoid types. The structure of 1 was determined by spectroscopic data
      interpretation in combination with molecular modeling calculations. The absolute
      stereochemistry of C-7 was assigned as S for compound 1 based on the obtained CD
      spectral data. Activity in the JB6 cell transformation assay was found for
      pomolic acid 3-acetate (4). All isolates obtained were evaluated in a
      cyclooxygenase-2 (COX-2) inhibition assay.

PMID- 16644528
TI  - Biflavonoids inhibited phosphatase of regenerating liver-3 (PRL-3).
AB  - Two biflavonoids, ginkgetin (1) and sciadopitysin (2), were isolated from the
      MeOH extract of the young branches of Taxus cuspidata, which inhibited
      phosphatase of regenerating liver-3 (PRL-3) with IC50 values of 25.8 and 46.2
      microM, respectively. This is the first report on PRL-3 inhibitors, isolated from
      natural sources.

PMID- 16644529
TI  - Phenolic constituents from Perovskia atriplicifolia.
AB  - Perovskoate, an isorinic acid derivative (1) and perovskoside, the catechol
      derivative (2) have been isolated from the ethyl acetate soluble fraction of the
      whole plant of Perovskia atriplicifolia and assigned the structure 3(7
      hydroxyphenyl)-2-hydroxy propanoic acid; (R)-form, 2-O-(6',7'-dihydroxy-E
      cinnamoyl) (1) and 2-methoxy-4-(undecyl-4'-O-beta-D-glucopyranosyl) phenol (2).
      In addition, caffeic acid (3) and ferulic acid (4) have been reported for the
      first time from this species. The structures of these compounds were assigned on
      the basis of 1D and 2D NMR techniques. The compound 1 showed significant
      inhibitory activity against lipoxygenase and weak to moderate activity against
      cholinesterases.

PMID- 16644530
TI  - Furoquinoline alkaloids from Melicope bonwickii (F.Muell.) T.Hartley.
AB  - Investigation on the leaves of Melicope bonwickii (F.Muell.) T.Hartley (Rutaceae)
      afforded a new 7-(2'-hydroxy-3'-chloroprenyloxy)-4-methoxyfuroquinoline (1)
      together with the known 7-(2',3'-epoxyprenyloxy)-4-methoxyfuroquinoline (2),
      evellerine (3) kokusaginine (4) and an amide aurantiamide acetate (5). Compounds
      1 and 2 showed significant activity against cervical cell lines (Hela).

PMID- 16644531
TI  - Synthesis and inhibitory activity of 8-substituted 2-deoxy-beta-KDO against CMP
      KDO synthetase.
AB  - 3-Deoxy-D-manno-octulosonate cytidyltransferase (CMP-KDO synthetase) is involved
      in the biosynthesis of lipopolysaccharide (LPS) which is an essential component
      of the outer membrane of gram-negative bacteria. New CMP-KDO synthetase
      inhibitors, 8-substituted derivatives of 2-deoxy-beta-KDO (2) have been prepared.
      Compounds 8, 11, 15 and 16 in which the 8-hydroxyl group of 2 is replaced by
      guanidine, di(carbamoylethyl)amino, p-methoxy- or p-nitro-benzyloxycarbonylamino,
      respectively affect moderately the CMP-KDO synthetase activity.

PMID- 16644532
TI  - Biocontrol efficacy of Cestrum diurnum L. (Solanaceae: Solanales) against the
      larval forms of Anopheles stephensi.
AB  - Cestrum diurnum L. (Solanaceae: Solanales) is a multistemmed shrub that is also
      known as 'Day Jasmine'. The efficacy of the plant as a strong biocontrol agent of
      the larval anopheline mosquito was evaluated in the laboratory and bioactive
      ingredients were characterized by thin layer chromatography (TLC) and infrared
      (IR) analysis. Thin layer chromatographic analysis revealed the presence of
      steroidal compound as a bioactive ingredient and IR analysis reported the
      presence of O-H group, C-S bond as a -CH2S group, H bonded -C=O group and
      carbonyl stress of esters. The LC50 value of the active ingredient was determined
      as 0.70, 0.89, 0.90 and 1.03 mg/100 mL-1, for 1st, 2nd, 3rd and 4th instar larva
      respectively in 24 h study period. The active component was analyzed by GLC and
      GLC-MS and altogether 14 components were detected.

PMID- 16644533
TI  - Cytotoxic sterols from marine-derived fungus Pennicillium sp.
AB  - A new sterol, ergosta-8(14), 22-diene-3,5,6,7-tetraol(3beta, 5alpha, 6beta,
      7alpha, 22E) (1), together with four known sterols ergosta-8(9), 22-diene-3,5,6,7
      tetraol (3beta, 5alpha, 6beta, 7alpha, 22E) (2), 5alpha,8alpha-epidioxy-24(S)
      methylcholesta-6,22-diene-3beta-ol (3), 5alpha,8alpha-epidioxy-24(S)
      methylcholesta-6,9(11), 22-triene-3beta-ol (4), 3beta,5alpha,9alpha
      trihydroxyergosta-7,22-diene-6-one (5) was isolated from marine fungus
      Pennicillium sp. Their structures were determined based on chemical analysis and
      spectral methods (IR, 1D and 2D NMR, HR-FAB-MS). Compounds 1-5 were evaluated for
      cytotoxicity against human liver cancer cell (Hep G), and most of them exhibited
      potent activity. Compound 1 display the highest potency with IC50 values 10.4
      microg mL-1.

PMID- 16644534
TI  - A new steroidal saponin from Agave shrevei.
AB  - A new steroidal saponin was isolated from the leaves of Agave shrevei. Its
      structure was established as 3-[O-beta-D-glucopyranosyl-(1-->2)-O-[O-beta-D
      glucopyranosyl-(1-->4)-O-[O-beta-D-glucopyranosyl-(1-->6)]-O-beta-D
      glucopyranosyl-(1-->4)-beta-D-galactopyranosyl)-oxy]-(3beta,5alpha,25R)
      spirostane. The structural identification was performed using detailed analyses
      of 1H- and 13C-NMR spectra including 2D NMR spectroscopic techniques (COSY,
      HETCOR, HMBC, and HMQC) and chemical conversions. The haemolytic activity of the
      steroidal saponin was evaluated using an in vitro assay.

PMID- 16644535
TI  - Antifilarial activity in vitro of polycarpol and 3-O-acetyl aleuritolic acid from
      cameroonian medicinal plants against Onchocerca gutturosa.
AB  - Previous results have revealed the antifilarial activities of crude extracts and
      pure compounds from some Cameroonian medicinal plants against Onchocerca volvulus
      and Onchocerca gutturosa. In our efforts to find new filaricidal agents against
      adult male O. gutturosa worms, we have isolated and screened three compounds:
      polycarpol and polyveoline from Polyalthia suaveolens (Annonaceae) and 3-O-acetyl
      aleuritolic acid from Discoglypremna caloneura (Euphorbiaceae). Only polycarpol
      and 3-O-acetyl aleuritolic acid exhibited significant inhibitory activities on
      the vitality of adult male worms of O. gutturosa using Amocarzine as positive
      control compound. The motility reduction values were 28.6 and 57.1%, and the
      inhibition of MTT reduction values 80.0 and 64.8% respectively.

PMID- 16644536
TI  - Philinopsides E and F, two new sulfated triterpene glycosides from the sea
      cucumber Pentacta quadrangularis.
AB  - Two new sulfated triterpene glycosides, philinopside E (1) and F (2), have been
      isolated from the sea cucumber Pentacta quadrangularis. Their structures have
      been established by extensive spectral analysis (NMR and MS) and chemical
      evidence. Glycoside 1 showed significant cytotoxicity (Ed(50) 0.75-3.50 microg
      mL(-1)) against ten tumor cell lines.

PMID- 16644537
TI  - Cucurbitacin glucosides from Citrullus colocynthis.
AB  - A new cucurbitacin glucoside 2-O-beta-D-glucopyranosyl-16alpha-20R-dihydroxy
      cucurbita-1,5,23E,25(26)-tetraen-3,11,22-trione (1) has been isolated from the
      methanolic extract of the fruits of Citrulluscolocynthis. The structure has been
      assigned on the basis of spectral analysis including 1D and 2D NMR techniques. In
      addition 2-O-beta-D-glucopyranosyl-cucurbitacin B (arvenin I) (2) and 2,25-di-O
      beta-D-glucopyranosyl-cucurbitacin L (3) are reported for the first time from
      this species.

PMID- 16644538
TI  - A geranylacetophenone from the leaves of Melicope ptelefolia.
AB  - The leaves of Melicope ptelefolia (Rutaceae) afforded a new acetophenone named
      2,4,6-trihydroxy-3-geranylacetophenone. The structure of the compound was
      established by mass and NMR spectroscopy.

PMID- 16644539
TI  - Comparative analysis of the oil and supercritical CO(2) extract of Artemisia
      arborescens L. and Helichrysum splendidum (Thunb.) Less.
AB  - Isolation of volatile concentrate from the dried leaves of Artemisia arborescens
      and of Helichrysum splendidum has been obtained by supercritical extraction with
      carbon dioxide. To obtain a pure volatile extract devoid of cuticular waxes, the
      extraction products were fractionated in two separators operating in series. A
      good extraction process was obtained operating at 90 bar and 50 degrees C in the
      extraction vessel, at 90 bar and at -5 degrees C in the first separator and at a
      pressure between 20 and 15 bar and temperatures in the range 10-20 degrees C in
      the second one. The composition of the volatile concentrate has been analyzed by
      GC/MS. The volatile concentrate of A. arborescens was found to contain: trans
      thujone (13.96%), camphor (6.15%) and chamazulene (5.95%). The main constituents
      in the extract of H. splendidum were: germacrene D-4-ol (17.08%), germacrene D
      (9.04%), bicyclogermacrene (8.79%) and delta-cadinene (8.43%). A comparison with
      the oils obtained by hydrodistillation is also given. The differences observed
      between the composition of the SFE volatile concentrates and of the
      hydrodistilled (HD) oils were relevant. Indeed, the HD oils had a blue color
      whereas the volatile concentrates were pale yellow. The HD oil of H. splendidum
      had a blue color due to the presence of guaiazulene (0.42% vs 0%), whereas the
      coloration of HD oil of A. arborecens was due to the high concentration of
      chamazulene (26.64% vs 3.37%).

PMID- 16644540
TI  - Evidence of cyanamide production in hairy vetch Vicia villosa.
AB  - Cyanamide (NH(2)CN) has recently been isolated as a plant growth inhibitor from
      Vicia villosa, which is the first discovery of cyanamide from natural sources. To
      reveal the presence of the biosynthesized cyanamide in plants, 3.4 mM potassium
      ((15)N)nitrate was administered to 15- to 35-day-old plants of V. villosa, from
      which the cyanamide was purified and subjected to GC/MS analysis. The isotopic
      ratio (15)N/((14)N + (15)N) of the cyanamide was calculated to be 0.143, while
      that of the cyanamide extracted from V. villosa grown in the presence of a
      natural N source was 0.0065. The (15)N-enrichment proved de novo biosynthesis of
      cyanamide.

PMID- 16644541
TI  - Sesquiterpene lactones from Crepis cameroonica (Asteraceae).
AB  - In addition to one known compound, 3beta,8alpha-dihydroxyguaian
      4(15),10(14),11(13)-trien-6,12 olide (8-desacylcynaropicrin) (3), two new
      sesquiterpene lactones have been isolated from the aerial parts of Crepis
      cameroonica. By means of spectroscopic analysis, the structures and relative
      configurations of the new compounds were established as 3beta,9beta
      dihydroxyguaian-4(15),10(14),11(13)-trien-6,12 olide (1) and 8alpha-hydroxy
      4alpha(13),11beta(15)-tetrahydrozaluzanin C (2). The in vitro antimicrobial
      spectrum of pure compounds and crude extracts are also reported.

PMID- 16644542
TI  - Lignans from Arnica species.
AB  - From four Arnica species (A. angustifolia Vahl ssp. attenuata (Greene) Maguire,
      A. lonchophylla Greene ssp. lonchophylla Maguire (flowerheads), A. chamissonis
      Less. ssp. foliosa (Nutt.) Maguire, A. montana L. (roots and rhizomes)) a total
      of twelve lignans of the furofuran-, dibenzylbutyrolactone- and
      dibenzylbutyrolactol-type were isolated. No report on lignans as constituents of
      Arnica species exists so far. Besides the known pinoresinol, epipinoresinol,
      phillygenin, matairesinol, nortrachelogenin and nortracheloside, six
      dibenzylbutyrolactol derivatives with different stereochemistry and substitution
      at C-9 were isolated and their structures elucidated by NMR spectroscopic and
      mass spectral analysis.

PMID- 16644543
TI  - Comparative analysis of the oil and supercritical CO(2) extract of Cymbopogon
      citratus Stapf.
AB  - Dried and ground leaves of lemon grass (Cymbopogon citratus Stapf.) were used as
      a matrix for supercritical extraction of essential oil with CO(2). The objective
      of this study was to analyze the influence of pressure on the supercritical
      extraction. A series of experiments were carried out, for 360 min, at 50 degrees
      C and at different pressures: 90, 100, 110 and 120 bar. Extraction conditions
      were chosen to maximize citral content in the extract oil. The collected extracts
      were analysed by GC-MS and their composition was compared with that of the
      essential oil isolated by hydrodistillation and by steam distillation. At higher
      solvent density the extract aspect changes passing from a characteristic yellow
      essential oil to yellowish semi-solid mass because of the extraction of high
      molecular mass compounds. The optimum conditions for citral extraction were 90
      bar and 50 degrees C, at these conditions citral represent more than 68% of the
      essential oil and the extraction yield was 0.65% while the yield obtained from
      hydrodistillation was 0.43% with a content of citral of 73%.

PMID- 16644544
TI  - ET743: Chemical analysis of the sea squirt Ecteinascidia turbinata ecosystem.
AB  - The sea squirt Ecteinascidia turbinata produces the powerful drug ET743. In this
      study Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) and
      Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS) are
      systematically used to measure elemental and molecular species in a Florida Keys
      mangrove ecosystem that contains the sea squirt. ICP-AES is used to measure the
      concentration of 27 elements down to the parts per billion level in 16 organisms
      and 3 sediment samples that reside in the mangrove ecosystem including turtle
      grass, blue crabs, fire sponge, and lettuce slugs. MALDI-MS is used to search for
      ET743 in these same organisms and sediment samples. A mass spectral feature
      corresponding to ET743 is identified in the extract of the sea squirt, red
      mangrove root (Rhizophera mangle), the schoolmaster snapper (Lutjanus griseus),
      and a sediment sample taken from the ecosystem. We use MALDI-MS to study the
      impact that various environmental conditions, such as UV light, I(2), cation
      binding (Fe(+3), Zn(+2), Pb(+2), Cu(+2)), metal oxide nanoparticles (FeO, CuO,
      TiO(2), ZnO, Al(2)O(3)), a common mineral (CaCO(3)), and extremes in acidity (0.1
      M HCl, 0.1 M NaOH) have on the ET743 structure. The data provide potential
      structures (degradation products, metal-ligand complexes, etc.) that might be
      present in organism or sedimentary extracts that are similar to ET743. We are
      studying the marine geochemistry of this ecosystem so a broth can be developed
      and tested for producing this marine natural product.

PMID- 16644545
TI  - The variability of composition of the volatile fraction of olive oil.
AB  - Aroma of olive oil is a very complex mixture of components. Analysis of head
      space of a series of virgin olive oil samples indicate a great variability of
      volatile substances composition in olives and these data probably should be
      related to the story of olives after collecting.

PMID- 16644546
TI  - Isolation and NMR spectroscopic clarification of the alkaloid 1,3,7
      trimethylguanine from the ascidian Eudistoma maculosum.
AB  - The alkaloid 1,3,7-trimethylguanine was isolated from the ascidian Eudistoma
      maculosum, and differences in the NMR spectroscopic data for this compound
      compared with data in the literature are due to ammonium salt formation.

PMID- 16644547
TI  - Inophyllin A, a new pyranoxanthone from Calophyllum inophyllum (Guttiferae).
AB  - In the authors' continuing search for new natural products, their recent studies
      on the roots of Calophyllum inophyllum (Guttiferae) have yielded a new prenylated
      pyranoxanthone, Inophyllin A together with the common triterpenes friedelin and
      stigmasterol. Structural elucidations of these compounds were achieved through
      (1)H, (13)C, DEPT, COSY, HSQC and HMBC experiments. The molecular mass was
      determined using MS techniques. The authors report here the isolation of and
      structural elucidation for Inophyllin A as well as its toxicity test result. The
      discovery of this new natural product from the unexploited Malaysian forest will
      certainly contribute to the search for potential natural larvicides.

PMID- 16644548
TI  - Two new benzylisoquinoline alkaloids from Papaver triniifolium.
AB  - From the aerial parts of Papaver triniifolium Boiss. (Papaveraceae) collected
      from Erzincan (Eastern Anatolia), two new benzylisoquinoline alkaloids,
      miltanthoridine and miltanthoridinone were isolated. Their structures were
      established through the use of UV, EIMS, and NMR techniques.

PMID- 16644549
TI  - Epibatidine and its analogues as nicotinic acetylcholine receptor agonist: an
      update.
AB  - Epibatidine (EPB) (1), an alkaloid isolated from the skin of the Ecuadorian
      poison frog, Epipedobates tricolor has attracted attention because of its
      exceptionally powerful analgesic properties: several hundred times greater than
      those of morphine, and the fact that it acts at nicotine rather than opiate
      receptors. Although the substance is toxic, it does serve as a lead compound in
      the development of drugs for pain relief as well as treatment of disorders whose
      pathogenesis involves nicotinic receptors. In this article, isolation, synthetic
      methods, effect on neuronal and neuromuscular nicotinic receptors, therapeutic
      potential, toxicity, nicotinic pharmacophore structural modifications related
      issues of 1 are discussed.

PMID- 16644550
TI  - Plant growth inhibitory activity of azo- and azoxyformamides from Calvatia
      craniiformis and Lycoperdon hiemale.
AB  - 4-Methoxybenzene-1-ONN-azoxyformamide (1), 4-methoxybenzene-1-azoformamide (2), 4
      hydroxyben-zene-1-azoformamide (3) and 4-hydroxybenzene-1-ONN-azoxyformamide (4)
      were isolated from the fruiting bodies of Calvatia craniiformis and Lycoperdon
      hiemale, respectively. Compounds 1 and 4 showed radicle growth inhibitory
      activities against the lettuce seedlings by more than 50% at 5.0 x 10(-1) mM,
      suggesting that the azoxy moiety contributes to the inhibitory activity. The
      plant growth inhibitory activities of 1, 2 and 4 against the barnyard millet
      seedlings were also measured.

PMID- 16644551
TI  - Taxonomical markers in two endemic plants of Sardinia: Verbascum conocarpum and
      Scrophularia trifoliata.
AB  - The monoterpenoid composition of Verbascum conocarpum and Scrophularia
      trifoliata, both endemic plants of Sardinia, was examined. The main
      chemotaxonomic markers of Scrophulariaceae, the iridoids aucubin, verbascoside
      and catalpol, were isolated.

PMID- 16644553
TI  - 3D-QSAR study on heterocyclic topoisomerase II inhibitors using CoMSIA.
AB  - Selective topoisomerase II (Topo II) inhibitors have interested to a great extent
      for the design of new antitumoral compounds in recent years. Comparative
      molecular similarity indices analysis (CoMSIA) was performed on a series of
      previously synthesized benzoxazole, benzimidazole, and oxazolo(4,5-b)pyridine
      derivatives as eukaryotic Topo II inhibitors. A training set of 16 heterocyclic
      compounds was used to establish the CoMSIA model. They were constructed and
      geometrically optimized using SYBYL v7.0. The predictive ability of the model was
      assessed using a test set of 7 compounds. The best model has demonstrated a good
      fit having r2 value of 0.968 and cross-validated coefficient q2 value as 0.562
      including steric and hydrophobic fields. The hydrophobic interactions showed a
      dominant role for increasing Topo II inhibitor activity and hydrophilic
      substituent was found more important than hydrophobic one on the 5 or 6 position
      of benzazole moiety. The model obtained from the present study can be useful for
      the modification and/or evaluation of the development of new Topo II inhibitors
      as potential antitumor compounds.

PMID- 16644554
TI  - A combined QSAR and partial order ranking approach to risk assessment.
AB  - QSAR generated data appear as an attractive alternative to experimental data as
      foreseen in the proposed new chemicals legislation REACH. A preliminary risk
      assessment for the aquatic environment can be based on few factors, i.e. the
      octanol-water partition coefficient (Kow), the vapour pressure (VP) and the
      potential biodegradability of the compound in combination with the predicted no
      effect concentration (PNEC) and the actual tonnage in which the substance is
      produced. Application of partial order ranking, allowing simultaneous inclusion
      of several parameters leads to a mutual prioritisation of the investigated
      substances, the prioritisation possibly being further analysed through the
      concept of linear extensions and average ranks. The ranking uses endpoint values
      (log Kow and log VP) derived from strictly linear 'noise-deficient' QSAR models
      as input parameters. Biodegradation estimates were adopted from the BioWin module
      of the EPI Suite. The population growth impairment of Tetrahymena pyriformis was
      used as a surrogate for fish lethality.

PMID- 16644555
TI  - Validation of a QSAR model for acute toxicity.
AB  - In the present study, a quantitative structure--activity relationship (QSAR)
      model has been developed for predicting acute toxicity to the fathead minnow
      (Pimephales promelas), the aim being to demonstrate how statistical validation
      and domain definition are both required to establish model validity and to
      provide reliable predictions. A dataset of 408 heterogeneous chemicals was
      modelled by a diverse set of theoretical molecular descriptors by using
      multivariate linear regression (MLR) and Genetic Algorithm-Variable Subset
      Selection (GA-VSS). This QSAR model was developed to generate reliable
      predictions of toxicity for organic chemicals not yet tested, so particular
      emphasis was given to statistical validity and applicability domain. External
      validation was performed by using OECD Screening Information Data Set (SIDS) data
      for 177 High Production Volume (HPV) chemicals, and a good predictivity was
      obtained (=72.1). The model was evaluated according to the OECD principles for
      QSAR validation, and compliance with all five principles was established. The
      model could therefore be useful for the regulatory assessment of chemicals. For
      example, it could be used to fill data gaps within its chemical domain and
      contribute to the prioritization of chemicals for aquatic toxicity testing.

PMID- 16644556
TI  - QSPRs for the prediction of photodegradation half-life of PCBs in n-hexane.
AB  - By partial least squares (PLS) regression analysis, a quantitative structure
      property relationship (QSPR) model was developed for photodegradation half-life
      (t1/2) of polychlorinated biphenyls (PCBs) in n-hexane solution under UV
      irradiation. Quantum chemical descriptors computed by PM3 Hamiltonian were used
      as predictor variables. The cross-validated value for the optimal QSPR model was
      0.589, indicating good predictive capability for log t1/2 values of PCBs in n
      hexane. The QSPR results show that standard heat of formation (DeltaHf), total
      energy (TE), and molecular weight (Mw) have dominant effect on t1/2 values of
      PCBs in n-hexane. Increasing DeltaHf and TE values or decreasing Mw values of the
      PCBs leads to decrease of log t1/2 values. In addition, increasing the largest
      negative atomic charge on a carbon atom and dipole moment of the PCBs leads to
      decrease of log t1/2 values.

PMID- 16644557
TI  - Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse
      transcriptase mutants.
AB  - Nevirapine (Viramune) belongs to the first generation of non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). Its efficiency is limited by drug resistant
      mutations, such as K103N and Y181C, so, the aim of this work was to design novel
      nevirapine analogues insensitive to the K103N and Y181C HIV-1 RT. 360 Nevirapine
      derivatives were designed using a combinatorial library design approach and these
      compounds were docked into the binding pocket of mutant HIV-1 RT enzyme
      structures, using the GOLD program. 124 Compounds having a GoldScore higher than
      that of nevirapine (55.00 and 52.00 for K103N and Y181C mutants, respectively)
      were first retrieved and submitted to a topological analysis with the SILVER
      program. Consequently, 31 compounds presenting a significant percentage of the
      surfaces buried upon binding (>80%) and exhibiting hydrogen bonds to either N103
      or C181 residues of the HIV-RT were selected. To ensure that these compounds had
      hydrogen bonding interaction to either N103 or C181 residues, their interaction
      energies were estimated by quantum chemical calculations (QCCs). Finally, QCCs
      represent an alternative method for performing post docking procedure.

PMID- 16644558
TI  - Prediction of estrogenicity: validation of a classification model.
AB  - (Q)SAR models can be used to reduce animal testing as well as to minimise the
      testing costs. In particular, classification models have been widely used for
      estimating endpoints with binary activity. The aim of the present study was to
      develop and validate a classification-based quantitative structure-activity
      relationship (QSAR) model for endocrine disruption, based on interpretable
      mechanistic descriptors related to estrogenic gene activation. The model predicts
      the presence or absence of estrogenic activity according to a pre-defined cut-off
      in activity as determined in a recombinant yeast assay. The experimental data was
      obtained from the literature. A two-descriptor classification model was developed
      that has the form of a decision tree. The predictivity of the model was evaluated
      by using an external test set and by taking into account the limitations
      associated with the applicability domain (AD) of the model. The AD was determined
      as coverage of the model descriptor space. After removing the compounds present
      in the training set and the compounds outside of the AD, the overall accuracy of
      classification of the test chemicals was used to assess the predictivity of the
      model. In addition, the model was shown to meet the OECD Principles for (Q)SAR
      Validation, making it potentially useful for regulatory purposes.

PMID- 16644559
TI  - Ecotoxicity prediction by adaptive fuzzy partitioning: comparing descriptors
      computed on 2D and 3D structures.
AB  - Classification models were established on four endpoints, i.e. trout, daphnia,
      quail and bee, including from 100 to 300 pesticides subdivided into 3 toxicity
      classes. For each species, five separate sets of molecular descriptors, computed
      by several software, were compared, including parameters related to 2D or 3D
      structures. The most relevant descriptors were selected with help of a procedure
      based on genetic algorithms. Then, structure-activity relationships were built by
      Adaptive Fuzzy Partition (AFP), a recursive partitioning method derived from
      Fuzzy Logic concepts.Globally, satisfactory results were obtained for each animal
      species. The best cross-validation and test set scores reached values of about 70
      75%. More important, the relationships derived from the descriptors calculated
      from 2D structures were superior or similar to those computed from 3D structures.
      These results underline that the long computational time employed to compute 3D
      descriptors is often useless to improve the prediction ability of the ecotoxicity
      models. Finally, the differences in the prediction ability between the different
      software used were quite reduced and show the possibility to use different
      descriptor packages for obtaining similar satisfactory models.

PMID- 16644560
TI  - Theory of mind and the right cerebral hemisphere: refining the scope of
      impairment.
AB  - The neuropsychological and functional characterisation of mental state
      attribution ("theory of mind" (ToM)) has been the focus of several recent
      studies. The literature contains opposing views on the functional specificity of
      ToM and on the neuroanatomical structures most relevant to ToM. Studies with
      brain-lesioned patients have consistently found ToM deficits associated with
      unilateral right hemisphere damage (RHD). Also, functional imaging performed with
      non-brain-injured adults implicates several specific neural regions, many of
      which are located in the right hemisphere. The present study examined the
      separation of ToM impairment from other deficits associated with brain injury. We
      tested 11 patients with unilateral right hemisphere damage (RHD) and 20 normal
      controls (NC) on a humour rating task, an emotion rating task, a graded (first
      order, second-order) ToM task with non-mentalistic control questions, and two
      ancillary measures: (1) Trails A and B, in order to assess overall level of
      impairment and set-shifting abilities associated with executive function, and (2)
      a homograph reading task to assess central coherence skills. Our findings
      indicate that RHD can result in a functionally specific deficit in attributing
      intentional states, particularly those involving second-order attributions.
      Performance on ToM questions was not reliably related to measures of cognitive
      impairment; however, performance on non-ToM control questions was reliably
      predicted by Trails A and B. We also discuss individual RHD patients' performance
      with attention to lesion locus. Our findings suggest that damage to the areas
      noted as specialised in neuroimaging studies may not affect ToM performance, and
      underscore the necessity of combining lesion and imaging studies in determining
      functional-anatomical relations.

PMID- 16644561
TI  - Cortical laminar thickness and column spacing in human temporal and inferior
      parietal lobes: intra-individual anatomical relations.
AB  - Harasty, Seldon, Chan, Halliday, and Harding (2003) and Seldon (2005) have
      proposed a "balloon model" which suggests that myelin growth stretches the
      cerebral cortex, causing the cortical thickness to decrease and the columnar
      spacing to increase, in turn affecting the cortical capacity to differentiate
      afferent signals. This has been tested using temporal lobe (area TA) and inferior
      parietal lobule (areas PG, PF) histological specimens from human donors. The
      temporal and inferior parietal regions differ in ways that have never been
      described. Correlations between the thickness of laminae II-III and columnar
      spacing in lamina III within individual cytoarchitectonic areas in both
      hemispheres of each donor were calculated. Those in areas PG/PF are predominantly
      negative in both hemispheres, as predicted by the model. This is also true for
      the left hemisphere TA, but the right hemisphere TA shows no correlations between
      thickness and spacing. Comparisons of thickness and spacing between left and
      right hemispheres in PG/PF of each donor show no consistent direction, whereas
      those in TA fairly consistently show thinner laminae and wider column intervals
      on the left. In the left area TA, females have thinner laminae than males. Thus,
      intra-area predictions of the balloon model are supported in most areas, whereas
      the hemispheric asymmetry predictions appear to hold for TA, but not for the
      inferior parietal lobe.

PMID- 16644562
TI  - Dichotic listening performance predicts language comprehension.
AB  - Dichotic listening performance is considered a reliable and valid procedure for
      the assessment of language lateralisation in the brain. However, the
      documentation of a relationship between language functions and dichotic listening
      performance is sparse, although it is accepted that dichotic listening measures
      language perception. In particular, language comprehension should show close
      correspondence to perception of language stimuli. In the present study, we tested
      samples of reading-impaired and normally achieving children between 10 and 13
      years of age with tests of reading skills, language comprehension, and dichotic
      listening to consonant-vowel (CV) syllables. A high correlation between the
      language scores and the dichotic listening performance was expected. However,
      since the left ear score is believed to be an error when assessing language
      laterality, covariation was expected for the right ear scores only. In addition,
      directing attention to one ear input was believed to reduce the influence of
      random factors, and thus show a more concise estimate of left hemisphere language
      capacity. Thus, a stronger correlation between language comprehension skills and
      the dichotic listening performance when attending to the right ear was expected.
      The analyses yielded a positive correlation between the right ear score in DL and
      language comprehension, an effect that was stronger when attending to the right
      ear. The present results confirm the assumption that dichotic listening with CV
      syllables measures an aspect of language perception and language skills that is
      related to general language comprehension.

PMID- 16644563
TI  - Handedness as a major determinant of functional cradling bias.
AB  - Cradling is an interactive activity, involving a manual component that is very
      often an integral part of cradling. Cradling, while doing something else with the
      free hand, is referred to here as functional cradling. This study examined the
      relationship between a person's handedness and what arm he or she prefers to use
      when functionally cradling a baby doll that resembles a newborn infant. A total
      of 765 participants took part in the experiment, 403 women and 362 men, between
      the ages of 4 and 86 years. Left- and mixed-handers were actively recruited. The
      sample consisted of 64.3% right-handed, 24.7% mixed-handed, and 11.0% left-handed
      participants. The results showed a clear tendency for participants to cradle in
      their non-dominant arm (p < .001). Furthermore, this tendency increased with age
      and it was present in both sexes, although significantly stronger in women than
      in men. On the other hand, experience with young children through younger
      siblings and/or being a parent did not increase the likelihood to cradle in the
      non-dominant arm. It is concluded that humans have a clear functional cradling
      preference for the non-dominant arm because this enables the dominant arm to
      engage in other tasks. This might also explain why previous studies have reported
      a universal left cradling bias because a right-handed majority (intuitively)
      keeps the dominant hand free when cradling.

PMID- 16644564
TI  - When advertising turns "cheeky"!
AB  - Portraits typically exhibit leftward posing biases, with people showing more of
      their left cheek than their right. The current study investigated posing biases
      in print advertising to determine whether the product advertised affects the
      posing bias. As the posing bias may be decreasing over time, we also investigated
      changes in posing biases over a span of more than 100 years. The current
      investigation coded 2664 advertisements from two time periods; advertisements
      were coded for target group of advertisement (men, women, both) and posing bias
      (rightward, leftward, or central). Unlike other studies that typically observe a
      leftward posing bias, print advertisements exhibit a rightward posing bias,
      regardless of time-frame. Thus, print advertisements differ greatly from
      portraits, which may relate to the purpose of advertisements and the role of
      attractiveness in advertising.

PMID- 16644565
TI  - Orientation of the stethoscope around the neck: a random phenomenon or an
      indicator of cerebral lateralisation? Cross-sectional survey.
AB  - This study aimed to determine whether the orientation of the stethoscope when
      placed around the neck by physicians is a random occurrence or if this represents
      a lateral preference. A cross-sectional questionnaire survey was conducted,
      recruiting 186 medical doctors of all grades from the University Hospital of
      Wales, Cardiff. Stethoscope orientation preference, and seven other measures of
      lateral preference (handedness, footedness, eyedness, earedness, hand clasping,
      arm folding, and leg crossing), were assessed. The percentage of right-type, left
      type, and indifferent-type orientation for each of the eight lateral preferences
      was determined, and 60%, 35%, and 5% of participants demonstrated right, left,
      and indifferent stethoscope orientation types, respectively. Stethoscope
      orientation preference correlated with handedness, footedness, earedness, and
      hand-clasping, but not with eyedness, arm-folding, or leg-crossing. Stethoscope
      orientation preference is not a chance phenomenon and may be an expression of
      cerebral dominance.

PMID- 16644567
TI  - Radiation induced brachial plexopathies.

PMID- 16644568
TI  - Epidemiology and etiology of non-Hodgkin lymphoma--a review.
AB  - The etiology of non-Hodgkin lymphoma, as well as its global dramatic rise in
      incidence during the past decades, remains largely unexplained. However, there is
      increasing awareness that this group of malignancies may entail not only
      clinical, morphological and molecular heterogeneity, but also considerable
      variations in terms of etiologic factors. In this review, epidemiologic patterns
      are summarized as well as current evidence of associations between various known
      or suspected risk factors for non-Hodgkin lymphoma overall or for any of its
      subtypes. Central pathogenetic mechanisms include immunosuppression, especially
      in relation to T-cell function and loss of control of latent EBV infection, and
      chronic antigen stimulation. Some degree of familiar aggregation also implies a
      role for genetic susceptibility. A number of recent investigations of non-Hodgkin
      lymphoma etiology will hopefully lead to a better understanding of the causes of
      these malignancies.

PMID- 16644569
TI  - Stable incidence of childhood and adult glioma in The Netherlands, 1989-2003.
AB  - Time trends in the incidence of glioma may reflect changes in the prevalence of
      environmental risk factors for glioma. We therefore investigated trends in the
      incidence of childhood and adult glioma in The Netherlands from 1989 to 2003. We
      used population-based incidence data from the Netherlands Cancer Registry. We
      calculated European standardised incidence rates for glioma, and stratified for
      age, gender and glioma subgroups. Changes in the incidence were estimated by
      calculating the Estimated Annual Percentage Change. Similar to other countries,
      the overall incidence of glioma was fairly stable in The Netherlands during the
      period 1989 to 2003, for both children and adults. In adult astrocytic glioma, a
      significantly increasing incidence of high-grade astrocytoma was balanced by
      simultaneous decreases of low-grade astrocytoma, astrocytoma with unknown
      malignancy grade and glioma of uncertain histology. Most of these time trends can
      be explained by improving detection and diagnostic precision. Stable incidence
      rates of adult and childhood glioma suggest that no major changes in
      environmental risk factors have occurred, which influenced the incidence of
      glioma in the studied period.

PMID- 16644570
TI  - Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant
      irradiation of patients with breast cancer--a review.
AB  - In order to increase the availability of adjuvant radiotherapy of breast cancer
      patients and make it more convenient and cheaper, in numerous cancer centres, the
      dose per fraction has been increased from 2 Gy to 2.25-2.75 Gy and the total dose
      has been decreased from 50 Gy to 40-45 Gy. The risk of developing any late
      complications after conventionally fractionated megavoltage radiotherapy is
      estimated to be below 1%. The aim of this review is to determine whether
      hypofractionated regimens increase the risk of damage to the brachial plexus. A
      review of the published literature shows that the use of doses per fraction in
      the range from 2.2 Gy to 4.58 Gy with the total doses between 43.5 Gy and 60 Gy
      causes a significant risk of brachial plexus injury which ranged from 1.7% up to
      73%. The risk of radiation induced brachial plexopathy was smaller than 1% using
      regimens with doses per fraction between 2.2 and 2.5 Gy with the total doses
      between 34 and 40 Gy. Surgical manipulations in the axilla and chemotherapy have
      to be taken into account as additional factors which may increase the risk of
      brachial plexopathy.

PMID- 16644571
TI  - Visual outcome, local tumour control, and eye preservation after 106Ru/Rh
      brachytherapy for choroidal melanoma.
AB  - To study the visual outcome, local tumour control, and eye preservation 5 years
      after ruthenium/rhodium 106 brachytherapy for choroidal melanoma. The study
      included 55 consecutive patients treated by 106Ru/Rh brachytherapy for a
      choroidal melanoma during the period 1988-2000 and followed through 2004. The 5
      year probability for not losing at least 5 Snellen lines was 59% (n = 45), for
      retaining a visual acuity of 0.33 or better was 28% (n = 34), and for retaining
      better than 0.1 was 40% (n = 45). The 5-year probability for no local recurrence
      was 73% and for eye preservation 72% (n = 55). 106Ru/Rh brachytherapy for
      choroidal melanoma resulted in a clinically significant vision loss, no local
      recurrence, and eye preservation in most patients after 5 years. 106Ru/Rh
      brachytherapy can be regarded as a good treatment option for small and medium
      sized tumours but not for large tumours.

PMID- 16644572
TI  - The Danish national guidelines for treatment of oral squamous cell carcinoma.
AB  - The treatment strategy for oral squamous cell carcinoma in Denmark has
      traditionally varied between the different head and neck oncology centres. A
      study group within the Danish Society for Head and Neck Oncology (DSHHO) was
      formed with the aim of optimising and standardising the treatment strategy. The
      approach was to use single modality treatment for stage I, stage II and some
      stage III and combined modality treatment for stage III and IV. Surgery was the
      preferred treatment when it was considered possible to perform a radical excision
      of the tumour and possible lymph node metastases with acceptable aesthetic and
      functional outcome. The implementation of a recognised national guideline
      facilitates prospective studies on a large well-characterised cohort. This
      increases the possibility of obtaining valid data on parameters such as
      morbidity, loco-regional control and survival. In addition the establishment of a
      reference program facilitates national monitoring of the treatment using defined
      indicators and standards.

PMID- 16644573
TI  - p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in
      xenografted human squamous cell carcinomas from head and neck.
AB  - To investigate the response of tumour growth to cisplatin treatment, in relation
      to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies
      from seven xenografted human squamous cell carcinomas from the head and neck were
      analysed with immunohistochemistry for p53 expression and cyclin D1 expression.
      Polymerase chain reaction-singlestranded conformation polymorphism was used to
      determine p53 mutations. Fluorescence in situ hybridization was performed to
      analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls)
      or cisplatin. After injection the tumour volume were measured. The inhibition of
      tumour growth by cisplatin was defined as the area under the growth curves, and
      compared with the growth curves of the tumours in the control group. Xenografts
      with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001)
      and also tumours with cyclin D1 amplification showed significantly higher
      resistance (p < 0.001).

PMID- 16644574
TI  - The effects of the vascular disrupting agents combretastatin A-4 disodium
      phosphate, 5,6-dimethylxanthenone-4-acetic acid and ZD6126 in a murine tumour: a
      comparative assessment using MRI and MRS.
AB  - The aim of this study was to use magnetic resonance (MR) techniques to non
      invasively compare the effects of the three leading vascular disrupting agents,
      namely combretastatin A-4 disodium phosphate (CA4DP), 5,6-dimethylxanthenone-4
      acetic acid (DMXAA) and ZD6126. A C3H mouse mammary carcinoma grown in the right
      rear foot of female CDF1 mice was used and treatments performed when tumours had
      reached 200 mm3 in volume. Drugs were prepared fresh before each experiment and
      intraperitoneally injected into restrained non-anaesthetised mice. Tumour
      response was evaluated using 31P-MR spectroscopy and T1- and T2- weighted imaging
      with a 7-Tesla, horizontal bore magnet, before and up to 24 hours after
      treatment. All three drugs significantly decreased bioenergetic status and pH,
      and did so in a time and dose dependent fashion, but there were differences; the
      decrease by CA4DP occurred more rapidly than for DMXAA or ZD6126, while DMXAA had
      a narrow window of activity compared to CA4DP and ZD6126. Changes in T1 weighted
      images for all three agents suggested a dose dependent increase in tumour oedema
      within three hours after treatment, consistent with an increase in vessel
      permeability. Using T2 weighted images there was some evidence of haemorrhagic
      necrosis by DMXAA, but such necrosis was limited following treatment with CA4DP
      or ZD6126.

PMID- 16644575
TI  - Suppression of VEGF transcription in renal cell carcinoma cells by pyrrole
      imidazole hairpin polyamides targeting the hypoxia responsive element.
AB  - Hypoxia inducible factor (HIF), a master regulator of critical genes for cell
      survival under hypoxic conditions, is known to be related to tumorigenesis and
      progression of renal cell carcinoma. N-methylpyrrole (Py)-N-methylimidazole (Im)
      hairpin polyamides are synthetic organic compounds that recognize and bind to the
      minor grooves of specific DNA sequences. We synthesized three Py-Im hairpin
      polyamides targeting the flanking sequences of hypoxia responsive element (HRE; a
      binding site of HIF) in the promoter region of the vascular endothelial growth
      factor (VEGF) gene. The effects of the polyamides on HIF-induced transcription
      were evaluated by a luciferase assay using a reporter plasmid containing a VEGF
      promoter. Real time reverse-transcriptase polymerase chain reaction and enzyme
      linked immunosorbent assay were performed to examine the effects of the
      polyamides on the transcription and secretion of VEGF in A498 renal cell
      carcinoma cells, which have a frame-shift mutation in the von Hippel-Lindau gene.
      A combination of three Py-Im hairpin polyamides suppressed HIF-induced
      transcription in reporter assays using 293 cells and successfully suppressed
      transcription and translation of the VEGF gene in A498 cells. Inhibition of the
      HIF-HRE interaction was confirmed by an electrophoresis mobility shift assay. An
      approach using Py-Im hairpin polyamides may be a new strategy for the treatment
      of renal cell carcinoma.

PMID- 16644576
TI  - How palliative care of cancer patients is organised between a university hospital
      and primary care in Finland.
AB  - The aim of this study was to find out how palliative care is organised between
      the Helsinki University Central Hospital (University Hospital) and primary care.
      The study consisted of 102 patients whose oncological treatment was terminated
      and the responsibility of palliative care was transferred to primary care. The
      patients were interviewed by phone using a structured questionnaire. Another
      questionnaire form was sent to the primary care physicians. Half of the patients
      were treated in more than one primary care unit. One third of the outpatients
      were unaware who was responsible for the care. Most of the patients wanted to be
      at home but this was achieved in less than half of the cases. Most patients were
      symptomatic while leaving the University Hospital and no improvement was seen
      thereafter. Every third patient reported of poor quality of palliative care in
      the primary care. Also the physicians reported a need for training in palliative
      care.

PMID- 16644577
TI  - Papillary carcinoma in a thyroglossal duct.

PMID- 16644578
TI  - "Burned out" phenomenon of the testis in retroperitoneal seminoma.

PMID- 16644579
TI  - Treatment and treatment considerations in a patient with advanced breast cancer
      and acute intermittent porphyria.

PMID- 16644580
TI  - Mutational analysis of PDPK1 kinase domain in gastric, colorectal and lung
      carcinomas.

PMID- 16644581
TI  - Absence of DKC1 exon 3 mutation in common human cancers.

PMID- 16644582
TI  - Acute small bowel perforation following preoperative radiotherapy and
      abdominoperineal resection: a case report.

PMID- 16644583
TI  - Treatment with valproic acid, all-trans retinoic acid (ATRA) and theophyllamine
      for 9 days caused a persistent increase in peripheral blood platelet counts for a
      patient with acute myelogenous leukemia.

PMID- 16644584
TI  - The role of Swedish tonal word accents in children with language impairment.
AB  - The present study was designed to examine the production of the Swedish tonal
      accents in children with language impairment and normal controls in order to
      verify previous findings. The productions of 25 children with linguistic
      impairment and their matched controls, aged 4;4-10;0 (mean age 5;11) were
      evaluated by ratings of fundamental frequency patterns, and by perceptual
      analysis by ten linguistically naive listeners to assess the distinctiveness of
      the accents. These methods give a more detailed description of the children's
      productions of tonal word accents. The results show that 60.8% of the children
      with language impairment have difficulties to produce the contrast of tonal word
      accents according to the F(0) patterns. The difference in the rating of the F(0)
      curves between the children with LI and their matched controls was significant.
      There is a significant positive correlation between the perceptual results and
      the F(0)-rating, indicating that the better a child was perceived, the better
      his/her F(0) production was rated. We conclude that the distinction between the
      tonal word accents is a difficult feature to acquire for Swedish children, which
      is shown both by acoustic and perceptual evaluations.

PMID- 16644585
TI  - An investigation of weak syllable processing in deaf children with cochlear
      implants.
AB  - In this study the influence of prosodic foot structure on the processing of weak
      syllables in children with cochlear implants (CI) was investigated. A battery of
      tests investigating processing of weak syllables in single and multi-word
      utterances was carried out on four groups of children: 15 children with CI
      developing spoken language as expected (Main CI); five children with CI reported
      to have additional speech and language problems; 15 age matched; and 15 language
      matched (LM) children with normal hearing (NH). Children in the main CI and, to a
      lesser extent, the LM groups processed footed weak syllables preferably over
      unfooted weak syllables (particularly as memory load increased). Thus, these
      children with CI appear to possess a similar Prosodic Hierarchy (PH) to their LM
      peers with NH, and possibly due to the impact of delayed and constrained exposure
      to audition on the development of linguistic processing and short-term memory,
      are influenced by its foot structure in the processing of weak syllables.

PMID- 16644586
TI  - Typically developing and speech-impaired children's adherence to the sonority
      hypothesis.
AB  - During phonological development, children frequently produce consonant clusters
      as consonant singletons, a process commonly referred to as cluster reduction. The
      principles of sonority may provide a theoretical basis for explaining patterns of
      cluster reduction evident in children's speech. Two studies were conducted to
      investigate whether children's word-initial cluster reductions adhered to the
      sonority hypothesis. Study one involved 16 children with typically developing
      speech, and study two involved 40 children with impaired speech. The children's
      consonant cluster productions characterized by a cluster reduction were analysed.
      When both groups of participants reduced word-initial clusters to a target
      consonant, the sonority hypothesis was adhered to; but when the clusters were
      reduced to a non-target consonant, the sonority hypothesis was violated. Analysis
      of target and non-target reductions revealed that some reductions of the
      individual clusters, and those within specific cluster categories, adhered to the
      sonority hypothesis while others did not. In light of these findings, it is
      suggested that although sonority is a valuable concept, it may not account for
      all patterns of cluster reduction evident in children's speech.

PMID- 16644587
TI  - Syllables per word in typical and delayed speech acquisition.
AB  - A number of authors have presented data on the word length (measured in
      syllables) in the spontaneous speech of children across the developmental period.
      These data suggest a developmental trend of increasing length with age. The
      current study sought to examine this possibility in more detail. Conversational
      speech data from 320 children with normal (or normalized) speech confirmed that
      the number of syllables per word in conversational speech increases significantly
      from age 3-8 years. Data from the conversational speech of 202 children with
      speech delay however showed no such trend. Reasons for the differences between
      the two groups are discussed.

PMID- 16644588
TI  - Measuring the intelligibility of conversational speech in children.
AB  - Conversational speech is the most socially-valid context for evaluating speech
      intelligibility, but it is not routinely examined. This may be because it is
      difficult to reliably count the number of words in the unintelligible portions of
      the sample. In this study four different approaches to dealing with this problem
      are examined. Each is based on the assumption that it is possible to perceive
      syllables in unintelligible strings even when the target words are unknown; these
      unintelligible syllables can then be used to estimate the number of
      unintelligible words in these samples using at least four different approaches.
      Preliminary data are presented for each of the four approaches based on
      conversational speech from two convenience samples including 320 children with
      normal (or normalized) speech and 202 children with speech delay. Differences
      among the four approaches are discussed.

PMID- 16644590
TI  - Impact of extraction conditions on the content of acrylamide in model systems and
      food.
AB  - It has recently been suggested that the analytical methods that have been
      developed to date for the determination of acrylamide (AA) may underestimate the
      concentration of AA in certain foods, because significantly higher results were
      obtained upon extraction of the food matrix under alkaline conditions. The
      present study employs food (potato, rye) and chemical model systems to better
      understand the tentative release of AA under high pH extraction conditions. The
      experimental design is based on the generation of AA in an environment containing
      an AA-isotopomer, and by comparing the ratio of AA, respectively the AA
      isotopomer, after extraction at pHs 7 and 12. The results show that the
      additional AA released is not due to improved extractability of AA from the food
      matrix, and should therefore be regarded as an extraction artefact. Strongly
      alkaline conditions seem to induce net formation of AA from water-soluble
      precursors formed during thermolysis.

PMID- 16644591
TI  - Structural elucidation of a tadalafil analogue found as an adulterant of a herbal
      product.
AB  - A tadalafil analogue and hydroxyhomosildenafil were isolated from a herbal
      product marketed for erectile dysfunction. The structure of the tadalafil
      analogue was elucidated using LC-UV, high resolution MS, ESI-MS/MS, IR, and NMR.
      The compound was determined to be (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)
      2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6] pyrido[3,4-b]indole-1,4-dione. This
      compound should be included as a target compound when screening for adulterants
      in herbal products. This is the first published paper on a tadalafil analogue and
      hydroxyhomosildenafil found as adulterants of a herbal product.

PMID- 16644592
TI  - Effect of fast green dye on some biophysical properties of thymocytes and
      splenocytes of albino mice.
AB  - Although fast green (FG) is widely used as food colorant by the cosmetics and
      drug industries, there is no evidence about whether FG affects leukocytes. The
      aim was to investigate the effect of FG on leukocytes. Male albino mice were
      subdivided into five equal groups: four of them were given 125, 250, 375 and 500
      mg kg(-1) bw day(-1) FG in drinking water for 44 days. The fifth (control group)
      was given pure water only. During the experimental period changes in body weight,
      lymphoid organs weight (absolute and relative) as well as the total count and
      viability of lymphoid cells for the treated groups showed that FG was an
      immunotoxic agent. The structural effects induced by FG on thymocytes and
      splenocytes were investigated through measurements of their dielectric spectra in
      the frequency range 20-100,000 Hz. The estimated dielectric parameters of the
      treated groups reflected the changes occurring to lymphocytes by FG
      administration and indicated that FG dye is an immunotoxic agent. It is shown
      that the dielectric methodology can be used for the identification of lymphocyte
      modification induced by food colorants.

PMID- 16644593
TI  - Effects of light level, time of harvest and position within field on the
      variability of tissue nitrate concentration in commercial crops of lettuce
      (Lactuca sativa) and endive (Cichorium endiva).
AB  - Seven commercial crops of lettuce and one crop of endive were sampled in order to
      study the variability in plant tissue nitrate concentration (TNC). Assuming that
      an appropriate sampling pattern was employed, ten plants were sufficient to give
      an acceptable estimate of the mean TNC. Short-term shading (24-48 h) had no
      significant effects on mean TNC, unlike the increase in TNC known to occur
      following dull periods 10-14 days before harvest. The effect on TNC of time of
      day harvested was significant, but there was no obvious pattern of diurnal
      variation. Averaged over all experiments, the coefficient of variation for TNC
      was in the order of 35%. Increasing the sample size from ten to 40 plants would
      only be expected to decrease the standard error of measurement of TNC from 16 to
      12% of the mean because of the underlying analytical error, which would remain
      constant.

PMID- 16644594
TI  - Simultaneous determination of four coccidiostats in eggs and broiler meat:
      validation of an LC-MS/MS method.
AB  - A published confirmatory method for the quantitative determination of four
      ionophoric coccidiostats (lasalocid, monensin, salinomycin and narasin) in eggs
      and broiler meat has been further developed. It is proposed for replacement of
      liquid chromatography methods previously used in analysis of ionophoric
      coccidiostats. The samples were extracted with acetonitrile and purified on a
      silica solid phase extraction column. Purified samples were analysed by liquid
      chromatography-mass spectrometry and the method, was validated according to the
      Commission Decision 2002/657/EC. The validation parameters selectivity,
      linearity, specificity, precision, recovery, decision limit (CCalpha) and
      detection capability (CCbeta) were determined. The recoveries of coccidiostats
      analysed ranged from 64-99% in eggs and 62-100% in broiler meat. CCalpha varied
      from 0.8-1.4 microg/kg in eggs and from 1.5-2.5 microg/kg in broiler meat. CCbeta
      varied from 0.9 microg/kg to 2.0 microg/kg in eggs and from 1.7-3.2 microg/kg in
      broiler meat.

PMID- 16644595
TI  - The determination of lead in sugar and sweets without digestion by electrothermal
      atomic absorption spectrometry (ETAAS) with a rhodium chemical modifier.
AB  - Reference methods for determining lead in food are usually time-consuming. This
      paper reports a straightforward procedure using electrothermal atomic absorption
      spectrometry (ETAAS), to determine lead (Pb) in fat-free sweets. Several chemical
      modifiers were examined and results showed that it is not necessary to digest the
      samples, when a rhodium (Rh) modifier was used. The samples were dissolved in
      nitric acid and the determination of Pb was performed by ETAAS, using Rh chemical
      modifier at a pyrolysis temperature of 900 degrees C and an atomization
      temperature of 1,500 degrees C. No ashing step was employed and aqueous standards
      were used, in the range 2-10 microg l(-1). The limit of quantification was 0.095
      mg kg(-1), and the accuracy of the method was verified by analysing certified
      reference materials.

PMID- 16644596
TI  - Uptake of thallium from naturally-contaminated soils into vegetables.
AB  - Thallium transfer from naturally (pedogeochemically) contaminated soils into
      vegetables was studied. Three different types of top-soil (heavy, medium, and
      light) were used for pot experiments. The soils were collected from areas with
      low, medium, and high levels of pedogeochemical thallium (0.3, 1.5 and 3.3 mg kg(
      1)). The samples of vegetables were collected and analysed. The total content of
      thallium in soil and the type of soil (heavy, medium and light), plant species
      and plant variety were found to be the main factors influencing thallium uptake
      by plants. The uptake of thallium from soils with naturally high pedogeochemical
      content of this element can be high enough to seriously endanger the food chain.
      These findings are very important because of the high toxicity of thallium and
      the absence of threshold limits for thallium in soils, agricultural products,
      feedstuffs and foodstuffs in most countries, including the Czech Republic.

PMID- 16644597
TI  - Distribution and elimination of fumonisin analogues in weaned piglets after oral
      administration of Fusarium verticillioides fungal culture.
AB  - The distribution and elimination of fumonisins after oral administration of 50 mg
      FB(1), 20 mg FB(2) and 5 mg FB(3) per animal day(-1) for 22 days was studied in
      weaned barrows. At the end of the trial, the lung, heart, liver, kidney, spleen,
      brain, serum, bile, muscle, fat, urine and faeces samples were collected and
      their content of fumonisins (FB(1), FB(2)) determined by LC-MS. The highest FB(1)
      concentrations were found in the liver (99.4 +/- 37.5 ng g(-1)) and kidneys (30.6
      +/- 10.1 ng g(-1)), whilst the highest average amount of FB(2) was in the liver
      (1.4 +/- 2.3 ng g(-1)) and fat (2.6 ng g(-1) +/- 4.8) samples. Comparing the
      FB(1)/FB(2) ratio in different organs (19/1), it was found that the ratio in the
      abdominal and subcutaneous fat samples (4/1) was markedly different from those in
      all other tissues, namely the relative proportion of FB(2) was higher in latter
      cases. Of the total quantity of FB(1), the 13% taken up during 5 days was
      excreted unchanged with the faeces and urine. On average, in the urine and
      faeces, FB(1) was detected in nine- and 14-fold quantities, as compared with
      FB(2).

PMID- 16644598
TI  - Aflatoxins, patulin and ergosterol contents of dried figs in Turkey.
AB  - Dried figs of three different categories, palatable, fluorescent, and cull, were
      investigated for their contents of aflatoxins (B(1), B(2), G(1) and G(2)),
      patulin, and ergosterol. Samples were obtained from four fig processing plants
      located in a major fig producing area in the Aegean Region in Turkey. Affinity
      column clean-up methods were employed for aflatoxins. All aflatoxins, patulin,
      and ergosterol were determined using high performance liquid chromatography.
      Palatable figs contaminated with trace amounts of aflatoxins, patulin, and
      ergosterol, so they posed no risk for the consumer when national and/or
      international regulatory limits were considered. Fluorescent figs were
      contaminated with high (117.9-471.9 ppb) aflatoxin levels and cull figs with high
      patulin (39.3-151.6 ppb) and ergosterol (4.5-18 ppm) levels. The total aflatoxins
      content was significantly correlated with the patulin content (r(2) = 0.813, p <
      0.002) and the ergosterol content (r(2) = 0.920, p < 0.002) only in fluorescent
      figs. However there was no significant correlation between patulin and ergosterol
      contents of fluorescent figs. Furthermore, there were no significant correlations
      between the contents of any two of the three substances in cull figs. This is the
      first report on the presence of patulin and its co-occurrence with aflatoxin in
      dried figs.

PMID- 16644599
TI  - A toxicokinetic model for the carry-over of dioxins and PCBs from feed and soil
      to eggs.
AB  - A mathematical model for the kinetics of carry-over of dioxins and dioxin-like
      PCBs from feed mixed with contaminated oil to eggs has been developed. This model
      incorporates uptake of the compounds over the gut wall and their subsequent
      transport by blood, distribution over the body, hepatic metabolism and excretion
      through egg yolk fat. The model is analysed with respect to the possibility of
      identifying as yet unknown model parameters by fitting these to the experimental
      data. The model was fitted to the experimental data on the carry-over from feed
      to eggs. The calibrated model was applied to calculate the steady-state
      concentrations in eggs which were compared to European Maximum Residue Levels for
      dioxins in feed and eggs, showing that these limits do not match. The feed limit
      of 0.75 ng TEQ/kg should be reduced to about 0.17 ng TEQ/kg in order to guarantee
      egg levels below the residue limit of 3 pg TEQ/g fat. Experimental results of
      carry-over from contaminated soil were used to estimate the absorption of dioxin
      like compounds from soils as compared to the absorption from feed, resulting in a
      value around 40 to 60% absorption from soil as compared to around 90% absorption
      from feed.

PMID- 16644600
TI  - Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination
      levels-- influence of mycotoxin binders on the carry-over from feed to eggs.
AB  - Laying hens were fed with compound feed containing six different levels of
      dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was
      followed by a period of 56 days on clean feed. Dioxin levels in feed varied from
      background levels to three times the current EU tolerance limit of 0.75 ng
      TEQ/kg. At all dose levels a rapid increase was observed in the dioxin levels in
      eggs. There was a clear linear dose-response relationship between the dioxin
      levels in eggs and feed. The feed containing 0.4 ng TEQ dioxins per kg resulted
      in egg levels just above the EU limit of 3 pg TEQ/g fat. Dioxin-like and
      indicator PCB residues followed a pattern very similar to that of dioxins.
      Exposure to the highest indicator PCB level of 32 microg/kg resulted in egg
      levels around 300 ng/g fat. Exposure to dioxins through contaminated soil, mixed
      at 10% into the feed, resulted in a similar carry-over as from feed. Mycotoxin
      binders, mixed at 0.5% into the feed, had little effect on the carry-over of
      dioxins from the feed to the egg. It can be concluded that consumption of feed or
      soil with even moderate levels of dioxins and dioxin-like PCBs rapidly results in
      increased levels in eggs. The current EU dioxin limit for feed cannot guarantee
      egg dioxin levels below the EU-limit.

PMID- 16644601
TI  - Approach to stochastic modelling of consumer exposure for any substance from
      canned foods using simulant migration data.
AB  - A two-dimensional probabilistic model was constructed to estimate the short-term
      dietary exposure of UK consumers to any generalized migrant from coated light
      metal food packaging. Using three UK National Dietary and Nutrition Surveys
      (NDNS) comprising 4-7-day dietary surveys for different age and gender groups,
      actual body weights and survey years, a sample representative of the dietary
      consumption of the UK population was obtained comprising around 4,200 food items.
      Interrogation of the raw data showed that the per capita consumption of food and
      beverage for an adult was 2.9 kg per person day(-1), which is comparable with the
      US FDA value of 3.0 kg. The packaging type of each food item was assigned from
      the survey descriptions or by sampling from distributions based upon market share
      information and expert judgement. Each food item was assigned to the relevant
      food simulant: A (aqueous), B (acidic) or D (fatty), so that simulant migration
      data could be used. The exposure model was used to evaluate exposure for a given
      level of migration and, conversely, the level of migration that could be
      tolerated whilst keeping within a target threshold exposure level. As examples,
      migration at 10 microg dm(-2) into fatty foods only resulted in an exposure
      ranging from 0.06 to 0.22 microg kg(-1) body (actual) weight day(-1) depending on
      the scenario. The model revealed that if migration from metal coatings was only
      into fatty foods, migration in the range 1.83-4.95 microg dm(2) (97.5th
      percentile, depending on the scenario) would give an exposure of less than 1.5
      microg per person day(-1). This is a toxicological threshold limit used in the
      USA. If migration into simulants A and B is also considered to be at the same
      level as that for simulant D, then the level of migration for the threshold to be
      reached is, not surprisingly, lower (0.64-0.87 microg dm(-2)) than that if
      migration were only into fatty foods. In this case, clearly the main contributors
      to the exposure were foodstuffs represented by simulants A and B because of their
      importance in the diet. These estimates are based on 4- or 7-day food diaries and
      chronic exposure over the long-term would be expected to be lower.

PMID- 16644602
TI  - Atovaquone plus cholestyramine in patients coinfected with Babesia microti and
      Borrelia burgdorferi refractory to other treatment.
AB  - Ten percent of US patients with Lyme disease are coinfected with Babesia microti.
      A double-blind, placebo-controlled, crossover trial enrolled 25 patients with
      confirmed Borrelia burgdorferi/B microti coinfection, abnormal visual contrast
      sensitivity (VCS), and persistent symptoms despite prior treatment with
      atovaquone and azithromycin. Patients were randomly assigned to atovaquone
      suspension or placebo plus cholestyramine for 3 weeks, were crossed over for 3
      weeks, and then received open-label atovaquone and cholestyramine for 6 weeks.
      Symptoms and VCS scores were recorded at baseline and after weeks 3, 6, 9, and
      12. Improvements in symptoms and VCS deficits were observed only after at least 9
      weeks of treatment. At week 12, 5 patients were asymptomatic, and 16 had a
      notable reduction in the number of symptoms. The entire cohort demonstrated
      significant increases in VCS scores. Adverse effects were rare. Patients
      coinfected with B burgdorferi and B microti derive measurable clinical benefit
      from prolonged treatment with atovaquone and cholestyramine. Longer-term
      combination therapy may be indicated.

PMID- 16644603
TI  - Tau protein as a serum marker of brain damage in mild traumatic brain injury:
      preliminary results.
AB  - The objective of this study was to investigate the diagnostic value of serum tau
      protein in determining the severity of traumatic brain injury in patients with
      mild traumatic brain injury (mTBI) and high-risk patients. Adult patients who
      presented to our emergency department (ED) with mTBI over 1 year were
      prospectively enrolled. Patients underwent cranial computed tomography (CT) and
      were subdivided into high- and low-risk groups, according to the probability of
      resultant intracranial injury. Serum tau levels of 60 patients and 20 healthy
      volunteers, who served as a control group, were measured. The mean age of the 60
      patients (45 males, 15 females) was 32.5 years (range, 15-66 y). Mean Glasgow
      Coma Scale (GCS) score was 14+/-0.6. CT scans demonstrated intracranial injury in
      11 patients (18.3%) and depressed fracture in 4 patients (6.7%). Serum tau levels
      of patients (188+/-210 pg/mL), compared with those of controls (86+/-48 pg/mL),
      were relatively higher; however, differences were not statistically significant
      (P=.445). Also, serum tau levels of high-risk patients (307+/-246 pg/mL) were
      significantly higher than those of low-risk patients (77+/-61 pg/mL) (P=.001). A
      total of 48 patients (80%) were accessible for follow-up after 6 months.
      Postconcussive syndrome was observed in 8 patients, 5 of whom had serum tau
      protein levels that were higher than those of the other 3 patients. However, no
      statistically significant difference was observed (P>.05). Investigators of the
      present study noted that serum tau levels in patients with mTBI were increased.
      Therefore, it is believed that this biomarker may prove helpful in identifying
      high-risk patients with mTBI. However, additional studies are needed to establish
      the diagnostic value of serum tau in detecting traumatic brain injury in patients
      with mTBI.

PMID- 16644604
TI  - Interferon-alpha2b may impair myelinization of rat optic nerve.
AB  - This story investigated the effects of interferon-alpha-2b (IFN-alpha2b) on the
      optic nerves of 17 adult male Wistar albino rats. Animals were divided into 3
      groups: 6 rats (group 1) received 7.5 units (5 mIU/m2) IFN-alpha2b-a normal
      treatment dose, and 6 (groups 2) received 30.0 units (20 mIU/m2)-a high dose; 5
      rats (control group) received 0.5 mL saline. Test substances were delivered by
      intraperitoneal injection 3 times a week for 3 weeks with animals under
      inhalation anesthesia. After the rats were sacrificed, their optic nerves were
      dissected, sectioned, and examined under an electron microscope. The mean
      thicknesses of the basal membranes of blood vessels were 86.354 nm in the control
      group, 104.297 nm in group 1, and 140.181 nm in group 2. Basal membrane changes
      in IFN groups were dose dependent. Mitochondrial swelling, degeneration,
      increased diameter of vacuoles, and vacuolization in the cytoplasm of
      oligodendrocytes and astrocytes were also observed. IFN-alpha2b has
      histopathologic effects on blood vessels and cells of the optic nerve.

PMID- 16644605
TI  - Comparing the relaxing effects of desflurane and sevoflurane on oxytocin-induced
      contractions of isolated myometrium in both pregnant and nonpregnant rats.
AB  - In this study, the effects of 2 volatile anesthetics, desflurane and sevoflurane,
      on oxytocin-induced contractions of isolated myometrium in pregnant and
      nonpregnant rats were compared. Twenty pregnant and 20 nonpregnant Wistar albino
      rats were studied at 19 to 20 days' gestation (term, 22 days). A total of 40
      myometrial strips were obtained from pregnant and nonpregnant rats, and each of
      these was randomly assigned to 1 of 4 groups (n=10, each group). After
      spontaneous myometrial contractions were induced in the De Jalon solution, the
      effects of 0.5, 1, and 2 minimum alveolar anesthetic concentrations (MAC) of
      desflurane or sevoflurane, in the absence and presence of oxytocin (2 x 10(-9)
      M), were investigated. Oxytocin significantly increased the amplitude and
      duration of spontaneous contractions in longitudinal myometrial strips (P<.05),
      but not the frequency. Both agents (except for 0.5 MAC in the nonpregnant group)
      inhibited the duration, amplitude, and frequency of induced contractions in a
      dose-dependent manner. The inhibitory potencies of desflurane and sevoflurane
      were similar. It was found that isolated strips of pregnant rat myometrium were
      more sensitive to the inhibitory effects of both agents than were the nonpregnant
      rat myometrial strips.

PMID- 16644606
TI  - Emergency service use by older people in Samsun, Turkey.
AB  - During the first 50 years of the 21st century, the world population aged 65 and
      older is expected to triple. Proper care of the older patient is one of the major
      priorities of many health care systems. In this descriptive study, patients
      treated and transported by 112 Emergency Help and Rescue Service in Samsun
      Province during the year 2004 were surveyed through review of command center
      records. All patients who were 65 years of age and older were included in the
      study. Collected data included patient sex and age, number of patients accessing
      emergency medical service (EMS) per hours of the day and per season, clinical
      diagnosis, and patient outcomes. In all, 2210 patients aged 65 years and older
      were identified; this group accounted for 24.5% of all records reviewed (n=9015).
      The rate of EMS use was highest in those older than 65 years of age (26 of
      1000/y). Similar associations of ambulance transportation with older age and off
      hour presentation were noted, as was increased usage during colder months of the
      year. Cardiovascular, neurologic, and respiratory problems were the 3 most
      frequent reasons for use of EMS. In almost three fourths of cases, outcome was
      recorded as transport to the hospital. Data presented here highlight the need for
      continued monitoring of EMS usage patterns so that planners will be prepared to
      accommodate the needs of the increasingly aging population.

PMID- 16644607
TI  - Resource utilization and costs of blood management services associated with knee
      and hip surgeries in US hospitals.
AB  - This article assesses the use and costs of blood transfusion during knee and hip
      surgery through a retrospective observational study of 92,223 discharged
      inpatients who had undergone knee or hip surgery from July 1, 2003, through June
      30, 2004; a sample of US hospitals that participated in the Perspective
      Comparative Database (Premier Inc., Charlotte, NC) was used. Descriptive and
      multivariate analyses were performed to determine the use and costs of allogeneic
      blood transfusion (ABT). The average cost of ABT per user ranged from $387
      (SD=$952) for red blood cells to $6585 (SD=$11,162) for cryoprecipitate.
      Utilization rates in the sample were as follows: antifibrinolytics, 0.14%;
      topical sealants, 3.24%; volume expanders, 3.89%; erythropoietin agents, 5.08%;
      and hypotensive anesthesia, 22.28%. Patients who were given volume expanders
      ($133.73, SD=$23.00, P<.01) or erythropoietin ($177.72, SD=$34.61, P<.01) had
      higher costs associated with ABT than did those who did not use volume expanders
      or erythropoietin. Patients who received hypotensive anesthesia (odds ratio
      [OR]=1.96; 95% confidence interval [CI], 1.87-2.06), a volume expander (OR=1.71;
      95% CI, 1.57- 1.85), a topical sealant (OR=1.61; 95% CI, 1.45-1.79), or an
      erythropoietic agent (OR=2.30; 95% CI, 2.06-2.57) had a greater likelihood of
      ABT. Investigators concluded that most transfusion reduction techniques are
      underused, or they do not reduce the burden of ABT associated with knee or hip
      surgery.

PMID- 16644608
TI  - Prospective comparative switch study from timolol 0.5% and latanoprost 0.005% to
      bimatoprost 0.03%.
AB  - This prospective study compared intraocular pressure (IOP) control,
      cardiorespiratory function, and adverse effects in 50 patients with glaucoma and
      ocular hypertension. Patients on topical combination timolol-latanoprost therapy
      were recruited. After they had used this combination for at least 2 months, they
      were switched to bimatoprost monotherapy. Full ocular examination and spirometric
      testing were performed; a questionnaire concerned with ocular symptoms was
      completed, and pulse rate was recorded. Two months later, mean IOP was similar
      with the combination (17.2 mm Hg) and with bimatoprost (16.4 mm Hg), but mean
      peak expiratory flow rate, ratio of forced expiratory volume in 1 second to
      forced vital capacity, and heart rate had increased significantly after the
      switch was made to bimatoprost. Adverse effects generally were similar with these
      regimens; however, the incidence of hyperemia doubled after the switch had been
      made. Bimatoprost and the timolol-latanoprost combination were equally
      efficacious in lowering IOP; bimatoprost had less of an effect on
      cardiorespiratory function.

PMID- 16644609
TI  - Efficacy and safety of prednisolone in patients with autoimmune hepatitis.
AB  - A retrospective cohort study involving 29 Japanese patients with autoimmune
      hepatitis (AIH) was performed to clarify factors that predict the efficacy of
      prednisolone and the occurrence of various serious adverse effects. Independent
      predictors were identified by logistic analysis and with use of the Cox
      proportional hazard model. Responses to prednisolone were noted in 28 patients,
      who were classified into the complete remission group (52%) or the relapse group
      (48%). Multivariate analysis identified alanine aminotransferase, alkaline
      phosphatase, and immoglobulin G levels as independent predictors of relapse. The
      adverse effects most frequently observed were diabetes mellitus (37.9%),
      psychiatric/ neurologic symptoms (34.5%), and circulatory symptoms (34.5%).
      Predictive factors included lactate dehydrogenase, albumin, and fasting blood
      glucose levels for diabetes mellitus, alkaline phosphatase and C-reactive protein
      for psychiatric/ neurologic symptoms, and autoimmune hepatitis score and lactate
      dehydrogenase for circulatory symptoms. Selection of an optimal treatment method
      for individual patients may be possible after the risks of relapse and adverse
      effects have been estimated.

PMID- 16644610
TI  - Antibiotic therapy for patients with spinal cord injury undergoing urologic
      procedures.
AB  - This prospective study was performed to determine whether gentamicin can be
      prescribed routinely to patients with spinal cord injury undergoing urologic
      procedures, or whether antibiotic therapy must be selected on the basis of recent
      urine microbiologic test results. Between January 2004 and June 2005, procedures
      were performed on 38 patients, all of whom were prescribed antibiotics on the
      basis of a microbiology report. Sixteen patients who underwent urologic surgery
      during 2003 and received gentamicin empirically served as a control group. The
      patients' clinical course was monitored for postprocedure sepsis. Only 12
      patients received gentamicin as the sole antibiotic; 10 patients required an
      additional antimicrobial for urine samples that grew more than 1 organism and
      contained bacteria resistant to gentamicin; 26 patients needed antibiotics other
      than gentamicin for gentamicin-resistant uropathogens. Three patients with
      organisms sensitive to gentamicin as well as another antibiotic received an agent
      considered less nephrotoxic than gentamicin. After the procedure, sepsis occurred
      in only 1 patient, a man with chronic lymphocytic leukemia and small cell
      carcinoma of the urinary bladder. Three control group patients developed a fever
      in excess of 39 degrees C. One of these patients did not require a change of
      antibiotic, another patient recovered after 3 changes of antibiotic, and the
      third patient recovered from septicemia after receiving ventilatory support.
      Antibiotics should be prescribed on the basis of recent urine microbiologic test
      results, and empiric therapy with gentamicin should be avoided in patients with
      spinal cord injury who are scheduled to undergo urologic procedures.

PMID- 16644611
TI  - Local irritant effects of topical oral sprays on oral mucosa in mice.
AB  - Topical oral sprays are frequently used to prevent and manage oropharyngeal
      inflammation and lesions. This study investigated the histopathologic changes
      noted in the oral mucosa of mice after topical application of 3 widely prescribed
      antibacterial products. The 25 animals were divided into 5 groups and treated for
      10 days with 2 sprays daily, as follows: group 1-chlorhexidine gluconate 0.12% +
      benzydamine hydrochloride 0.15%; group 2-benzydamine 0.27 mg/0.18 mL x 30 mL;
      group 3-chlorhexidine 0.2%; group 4-fusafungine 1%; and group 5 (cohort)
      physiologic serum. On day 10 after drug administration, biopsy specimens were
      taken from the oropharyngeal mucosa of the tongue, the cheek mucosa, and the
      tongue base; these were examined under a light microscope and were classified as
      normal or pathologic. All topical oral sprays produced some degree of
      histopathologic change, such as hyperplasia, fibrosis, low-grade dysplasia,
      congestion, or edema. The local irritant effects of topical oral sprays should be
      considered when treatment is selected for patients with oropharyngeal disorder.

PMID- 16644612
TI  - Efficacy and safety of once- and twice-daily formulations of molsidomine in
      patients with stable angina pectoris: double-blind and open-label studies.
AB  - Molsidomine, a sydnonimine acting as a heterocyclic direct nitric oxide donor,
      has been used for many years in several European countries for the treatment of
      patients with stable angina pectoris. The efficacy and tolerability of a novel
      once-daily 16-mg formulation of molsidomine (M16) were compared with those of the
      currently used twice-daily 8-mg molsidomine tablet (M8) in 666 patients. Study 1,
      a multicenter, randomized, double-blind, placebo-controlled, twin crossover
      study, involved 533 patients given acute and 2-week treatment with each drug
      formulation. Study 2, a multicenter, open-label, sequential, add-on trial,
      compared M16 and M8 in 133 patients. Drug effects on exercise capacity (study 1
      only), frequency of anginal attacks and consumption of short-acting
      itroderivatives, and incidence of adverse events (AEs) were evaluated. Compared
      with placebo, M16 increased exercise capacity by 15% (P<.001) at the start of
      study 1 and by 13% (P<.001) after 2 weeks' treatment, and was not inferior to M8.
      In terms of anginal attack frequency and nitroderivative consumption, M16 was not
      inferior to M8 in either study. Moreover, compared with M8, M16 produced a
      statistically and clinically significant reduction in the incidence of anginal
      attacks in elderly (>/=75 y) but not in younger patients (<75 y) (study 2), nor
      in patients from study 1. No significant difference from M8 was found in either
      study in short-acting nitroderivative consumption. No tolerance to M8 or M16 was
      observed after 2-week treatment. No statistically significant differences in
      incidences of all AEs and drug-related AEs were observed between M16 and M8 in
      either study. The same held true for proportions of patients experiencing AEs and
      drug-related AEs on M16 vs M8: in study 1-14.3% and 11.8% for all AEs (P=.218),
      6.9% and 5.4% for drug-related AEs (P=.280); in study 2-1.3% and 1.3% for all
      AEs, 0% and 1.3% for drug-related AEs (P>.10) in young patients; and in the
      elderly, 3.6% and 0% for drug-related AEs (P>.10). Only the proportion of elderly
      patients with all AEs was significantly higher with M16 than with M8: 14.5% vs
      1.8% (P=.039). M16 once daily was effective and well tolerated in investigated
      patients with stable angina pectoris, particularly the elderly, affording 24
      hours of therapeutic activity. M16 was not inferior to M8 given twice daily in
      terms of efficacy, safety profile, and tolerability.

PMID- 16644613
TI  - Effect of smoking on pregnancy-associated plasma protein A, free beta-human
      chorionic gonadotropin, and nuchal translucency in the first trimester of
      pregnancy.
AB  - Data were collected from 1275 pregnant Turkish women screened prospectively for
      chromosomal anomalies to determine whether first-trimester levels of maternal
      serum pregnancy-associated plasma protein A (PAPP-A) and free beta-human
      chorionic gonadotropin (beta-hCG) and the thickness of nuchal translucency are
      affected by smoking and other covariables. Only normal singleton pregnancies were
      included. After weight correction, comparisons were made between smokers and
      nonsmokers. Mean values of PAPP-A and beta-hCG were reduced in women who smoked 5
      or more cigarettes a day compared with nonsmokers. The median beta-hCG level
      decreased significantly as gravidity and parity increased; no effect was noted on
      PAPP-A. Median PAPP-A and beta-hCG levels tended to increase, but not
      significantly in women who had had 2 or more miscarriages. Smoking alters
      maternal levels of serum analytes, with the magnitude of the impact related to
      the number of cigarettes smoked per day. This effect can be detected in the first
      trimester of pregnancy.

PMID- 16644614
TI  - Vitiligo associated with pegylated interferon and ribavirin treatment of patients
      with chronic hepatitis C: a case report.
AB  - The use of pegylated interferon (PEG-IFN) and ribavirin is considered standard
      therapy for patients with chronic hepatitis C. Many adverse effects of IFN appear
      to be of autoimmune origin. Vitiligo is a hypomelanotic disease, whose cause,
      despite many investigations, remains unknown, although some evidence points to an
      autoimmune pathogenesis. This report describes a case of vitiligo that occurred
      during the third month of treatment with PEG-IFN and ribavirin. The sustained
      virologic response was the result of a 52-week regimen; however, hypomelanotic
      cutaneous patches persisted. Autoimmune adverse effects of IFN therapy, which may
      include vitiligo, should be carefully monitored. The decision about whether to
      discontinue treatment should be discussed with the patient, who must be informed
      that the lesions may persist.

PMID- 16644615
TI  - Application of physiology-based pharmacokinetic and pharmacodynamic modeling to
      individualized target-controlled propofol infusions.
AB  - This study compared the ability of the physiology-based pharmacokinetic (PBPK)
      model with that of compartmental models used in propofol infusion devices to
      predict the pharmacokinetics and pharmacodynamics of propofol in various patient
      groups (children, pregnant women, young men, normal weight adults, and obese
      adults). With a PBPK model, loss of consciousness (LOC) and recovery of
      consciousness (ROC) corresponded to a narrow range of brain tissue concentrations
      (2.2-4.0 mg/L). With the compartmental models, predicted effect concentrations
      were also within a narrow range at LOC, but were outside the range at ROC. In
      individuals of normal weight, coefficients of variation (CV) of the predicted
      brain or effect concentrations at LOC were in a similar range-between 18% and
      32%. In obese individuals, however, interindividual CV values for brain or effect
      concentrations were 41% (PBPK) and 93% (compartmental). This comparison suggests
      the increased flexibility of PBPK models over compartmental models, the latter of
      which rely heavily on the patient group from which the model was derived. The
      incorporation of PBPK models may provide target-controlled infusions with
      enhanced ability to predict response in a wide variety of patients.

PMID- 16644616
TI  - Inguinal approach in adult hydrocele surgery: preliminary randomized study.
AB  - This prospective study compared the effects of scrotal and inguinal approaches in
      hydrocele repair. Thirty-two adult patients, enrolled between January 1994 and
      May 2000, were randomly assigned to an inguinal (n=17) or a scrotal (n=15)
      approach. Scrotal size (at the surgical site) was measured preoperatively and
      postoperatively. Edema, infection, and hematoma formation were evaluated on the
      first, second, and third days after operation. Hematoma occurred in 4 patients in
      the scrotal approach group and in 1 patient in the inguinal approach group.
      Scrotal size was significantly smaller in the scrotal approach group on all
      postoperative evaluation days. Three months after surgery, all patients in both
      groups were free of hydrocele. The inguinal approach is a feasible option in the
      surgical treatment of adults with hydrocele; it results in less edema than is
      noted with the scrotal approach. Larger studies are needed to confirm these
      results.

PMID- 16644617
TI  - Adult ileal intussusception: an unusual emergency condition.
AB  - Adult intussusception occurs infrequently and differs from the childhood
      condition in its presentation, cause, and treatment. Nonspecific symptoms can
      delay diagnosis; most cases are diagnosed at emergency laparotomy. Increased use
      of computed tomographic scanning to evaluate patients with abdominal pain can
      enhance reliable preoperative diagnosis. Treatment entails simple bowel resection
      in most cases. Reduction is controversial, especially in cases of colonic
      intussusception. This report describes the diagnosis and management of a case of
      adult ileal intussusception caused by an inflammatory fibroid polyp-a rare lesion
      of the gastrointestinal tract.

PMID- 16644618
TI  - Treatment of patients with venous insufficiency with fresh plant horse chestnut
      seed extract: a review of 5 clinical studies.
AB  - Extracts from the seed of the horse chestnut (Aesculus hippocastanum L.) have
      traditionally been used to treat patients with chronic venous insufficiency and
      to alleviate its associated symptoms, including lower leg swelling. The efficacy
      of preparations that contain horse chestnut seed extract (HCSE) is believed to be
      due largely to an inhibitory effect on the catalytic breakdown of capillary wall
      proteoglycans. Aesculaforce is a fresh plant HCSE that is available as an oral
      tincture, as tablets (20 mg or 50 mg), and as topical gel. Four clinical trials
      in patients with chronic venous insufficiency and 1 study in patients with
      varicose veins demonstrated the effectiveness of these preparations through the
      objective measure of reduction in lower leg edema and the subjective alleviation
      of leg pain, heaviness, and itching. Safe, well tolerated, and acceptable to
      patients, the fresh plant HCSE preparation Aesculaforce offers a real alternative
      in the treatment of patients with mild to moderate venous insufficiency.

PMID- 16644619
TI  - Safety and tolerance of ester-C compared with regular ascorbic acid.
AB  - The goal of this randomized, double-blind crossover clinical trial in 50 healthy
      volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium
      ascorbate causes fewer epigastric adverse effects than are produced by regular
      ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The
      study comprised an observation period of 9 days (phase 1 medication for 3
      consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3
      consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1
      of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice
      versa. During the course of the study, 3 examinations for the evaluation of
      epigastric adverse effects were performed (on days 0, 3, and 9). Participants
      used a diary to record epigastric adverse effects on a daily basis. In total, 28
      (56%) of 50 participants reported 88 epigastric adverse effects of mild to
      moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake
      of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of
      Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very
      good" by only 54%. This difference is statistically significant (P<.05).
      Investigators concluded that Ester-C compared with AA caused significantly fewer
      epigastric adverse effects in participants sensitive to acidic foods and that
      Ester-C is much better tolerated.

PMID- 16644620
TI  - Tc-99m MIBI uptake in traumatic vertebral fractures and metastatic vertebral
      lesions: comparison with Tc-99m MDP.
AB  - This study compared technetium-99m-hexakis-2-methoxyisobutyl-isonitrile (Tc-99m
      MIBI) with technetium-99m methylene iphosphonate (Tc-99m MDP) to determine
      whether Tc-99m MIBI could distinguish vertebral metastases from traumatic
      vertebral fractures. Twenty patients with traumatic vertebral fracture (and no
      malignant disease) and 14 patients with metastatic vertebral lesions were
      evaluated. Three to 4 hours after intravenous injection of Tc-99m MDP, images of
      the vertebrae in all patients were obtained. Corresponding Tc-99m MIBI images
      were acquired within 4 days after the Tc-99m MDP bone images were obtained.
      Computed tomography and magnetic resonance imaging demonstrated 24 vertebral
      traumatic fractures and 44 vertebral metastases. On conventional bone scans, Tc
      99m MDP activity was increased in 92% of vertebral fractures and in 100% of
      vertebral metastases. However, on MIBI scans, no abnormal findings were observed
      in the vertebrae with fracture, although increased activity was seen in 73% of
      vertebral metastases. In this study, traumatic vertebral fractures tended to
      display no pathologic increases in Tc-99m MIBI uptake, whereas bone metastases
      usually appeared with high uptake. In light of the excellent specificity of Tc
      99m MIBI scans compared with Tc-99m MDP bone scans, imaging studies that use Tc
      99m MIBI scans may play an important complementary role in differentiating
      vertebral metastases from traumatic vertebral fractures.

PMID- 16644621
TI  - Structured personal diabetes care in primary health care affects only women's
      HbA1c.
AB  - OBJECTIVE: Diabetic men and women differ in lifestyle and attitudes toward
      diabetes and may benefit differently from interventions to improve glycemic
      control. We explored the relation between HbA1c (A1C), sex, treatment allocation,
      and their interactions with behavioral and attitudinal characteristics in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Six years after their
      diabetes diagnosis, a population-based sample of 874 primary care patients
      cluster-randomized to receive structured personal care or routine care reported
      lifestyle, medication, social support, diabetes-related consultations, and
      attitudes toward diabetes. Multivariate analyses were applied, split by sex.
      RESULTS: A marked intervention effect on A1C was confined to the structured
      personal care women. The median A1C was 8.4% in structured personal care women
      and 9.2% in routine care women (P < 0.0001) and 8.5% in structured personal care
      men and 8.9% in routine care men (P = 0.052). Routine care women had a 1.10 times
      higher A1C than structured personal care women, (P < 0.0001, adjusted analysis).
      Structured personal care women had relatively more consultations than routine
      care women, but neither number of consultations nor other covariates helped to
      explain the sex difference in A1C. Irrespective of treatment allocation, women
      had more adaptive attitudes toward diabetes but lacked support compared with men.
      CONCLUSIONS: In this study, the observed effect of structured personal care on
      A1C was present only among women, possibly because they were more inclined to
      comply with regular follow-up and had a tendency to have a more adaptive attitude
      toward diabetes.

PMID- 16644622
TI  - A clinical screening tool identifies autoimmune diabetes in adults.
AB  - OBJECTIVE: Latent autoimmune diabetes in adults (LADA) is defined as adult-onset
      diabetes with circulating islet antibodies but not requiring insulin therapy
      initially. Diagnosing LADA has treatment implications because of the high risk of
      progression to insulin dependency. Currently, there are no recommendations for
      islet antibody testing in adult-onset diabetes. In this study, we aimed to
      develop a clinical screening tool to identify adults at high risk of LADA who
      require islet antibody testing. RESEARCH DESIGN AND METHODS: Subjects with LADA
      (n = 102, GAD antibody [GADA]+) and type 2 diabetes (n = 111, GADA-) (aged 30-75
      years) were interviewed retrospectively. The clinical features documented were
      age of onset, acute symptoms of hyperglycemia, BMI, and personal and family
      history of autoimmune disease. Any clinical feature that was significantly more
      frequent in LADA was designated as a distinguishing clinical feature. In each
      subject, a "LADA clinical risk score," based on the total number of
      distinguishing features, was calculated. A prospective study of adults with newly
      diagnosed diabetes (n = 130) was used to determine whether the LADA clinical risk
      score could identify LADA. RESULTS: In the retrospective study, five clinical
      features were more frequent in LADA compared with type 2 diabetes at diagnosis:
      1) age of onset <50 years (P < 0.0001), 2) acute symptoms (P < 0.0001), 3) BMI
      <25 kg/m2 (P = 0.0004), 4) personal history of autoimmune disease (P = 0.011),
      and 5) family history of autoimmune disease (P = 0.024). In the prospective
      study, the presence of at least two of these distinguishing clinical features
      (LADA clinical risk score > or =2) had a 90% sensitivity and 71% specificity for
      identifying LADA and a negative predictive value for a LADA clinical risk score <
      or =1 of 99%. CONCLUSIONS: At least two distinguishing clinical features are
      found in a majority of patients with LADA at diagnosis and can be used to
      identify adults with diabetes at higher risk for LADA.

PMID- 16644623
TI  - Consumption of both resistant starch and beta-glucan improves postprandial plasma
      glucose and insulin in women.
AB  - OBJECTIVE: Consumption of a meal high in resistant starch or soluble fiber (beta
      glucan) decreases peak insulin and glucose concentrations and areas under the
      curve (AUCs). The objective was to determine whether the effects of soluble fiber
      and resistant starch on glycemic variables are additive. RESEARCH DESIGN AND
      METHODS: Ten normal-weight (43.5 years of age, BMI 22.0 kg/m2) and 10 overweight
      women (43.3 years of age, BMI 30.4 kg/m2) consumed 10 tolerance meals in a Latin
      square design. Meals (1 g carbohydrate/kg body wt) were glucose alone or muffins
      made with different levels of soluble fiber (0.26, 0.68, or 2.3 g beta-glucan/100
      g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g
      muffin). RESULTS: Overweight subjects had plasma insulin concentrations higher
      than those of normal-weight subjects but maintained similar plasma glucose
      levels. Compared with low beta-glucan-low resistant starch muffins, glucose and
      insulin AUC decreased when beta-glucan (17 and 33%, respectively) or resistant
      starch (24 and 38%, respectively) content was increased. The greatest AUC
      reduction occurred after meals containing both high beta-glucan-high resistant
      starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight
      women were somewhat more insulin resistant than control women. CONCLUSIONS:
      Soluble fiber appears to have a greater effect on postprandial insulin response
      while glucose reduction is greater after resistant starch from high-amylose
      cornstarch. The reduction in glycemic response was enhanced by combining
      resistant starch and soluble fiber. Consumption of foods containing moderate
      amounts of these fibers may improve glucose metabolism in both normal and
      overweight women.

PMID- 16644624
TI  - Diet of adolescents with and without diabetes: Trading candy for potato chips?
AB  - OBJECTIVE: To compare the dietary intake of adolescents with type 1 diabetes with
      that of adolescents without diabetes matched on age, sex, and year in school and
      to compare the diets of both groups with recommendations. RESEARCH DESIGN AND
      METHODS: Participants were 132 adolescents with type 1 diabetes, recruited from
      Children's Hospital of Pittsburgh, and 131 adolescents without diabetes ranging
      in age from 10.70 to 14.21 years. Dietary intake was assessed with three 24-h
      recall interviews with each participant and one parent. Percentage of calories
      from protein, carbohydrates, and total fat; amount of each type of fat; and
      amount of cholesterol, fiber, and sugar were calculated as averages across 3
      days. RESULTS: Adolescents with diabetes took in less total energy than
      recommended. The percentage of calories from carbohydrates and protein were
      within recommendations for adolescents with and without diabetes, but adolescents
      with diabetes exceeded the recommended fat intake. The diet of adolescents with
      diabetes consisted of a greater percentage of fat and protein and a smaller
      percentage of carbohydrates relative to adolescents without diabetes. Adolescents
      without diabetes consumed more sugar, while adolescents with diabetes took in
      more of all components of fat than adolescents without diabetes. Male subjects
      with diabetes had an especially high intake of saturated fat. CONCLUSIONS:
      Adolescents with type 1 diabetes consume fewer calories from carbohydrates but
      more calories from fat than adolescents without diabetes and exceed the
      recommended levels of fat intake. These findings are of concern given the risk
      that type 1 diabetes poses for cardiovascular disease.

PMID- 16644625
TI  - A new wound-based severity score for diabetic foot ulcers: A prospective analysis
      of 1,000 patients.
AB  - OBJECTIVE: Several well-accepted classification systems are available for
      diabetic foot ulcers. However, there are only a few and scientifically not
      validated severity scores. The aim of this study was to establish a new wound
      based clinical scoring system for diabetic foot ulcers suitable for daily
      clinical practice anticipating chances for healing and risk of amputation.
      RESEARCH DESIGN AND METHODS: Four clinically defined parameters, namely palpable
      pedal pulses, probing to bone, ulcer location, and presence of multiple
      ulcerations, were prospectively assessed in 1,000 consecutive patients. In the
      next step, a new diabetic ulcer severity score (DUSS) was created from these
      parameters. Palpable pedal pulses were categorized by the absence (scored as 1)
      or presence (scored as 0) of pedal pulses, while probing to bone was defined as
      yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe
      (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations
      were graded as 1 compared with those with single ulcers (scored as 0). The DUSS
      was calculated by adding these separate gradings to a theoretical maximum of 4.
      Wounds were followed-up for 365 days or until healing or amputation if earlier.
      Probability of healing and risk of amputation were calculated by the Kaplan-Meier
      method. RESULTS: Uni- and multivariate analyses showed a significantly higher
      probability of healing for patients with palpable pulses, no probing to bone, toe
      ulcers, and absence of multiple ulcerations. When patients were divided into
      subgroups with the same DUSS, we found significantly different probabilities for
      healing. We showed a decreasing probability of healing for ulcers with a high
      DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one
      score point reduced the chance for healing by 35%. Similarly, the higher the
      ulcer score, the larger the initial wound area, the longer the wound history, and
      the more likely the need for surgery or hospitalization. CONCLUSIONS: The DUSS
      categorizes different ulcers into subgroups with specific severity and similar
      clinical outcome. Using this score, the probabilities for healing, amputation,
      need for surgery, and hospitalization are predictable with high accuracy. This
      might be useful for the anticipation of health care costs and for comparison of
      subgroups of patients in clinical studies.

PMID- 16644626
TI  - Parent perceptions of caring for adolescents with type 2 diabetes.
AB  - OBJECTIVE: No studies have been performed to examine parent perceptions of caring
      for adolescents with type 2 diabetes. In this qualitative study, we examined
      parent perceptions of barriers and strategies to address barriers to self-care in
      adolescents with type 2 diabetes. RESEARCH DESIGN AND METHODS: Families of
      adolescents with type 2 diabetes were recruited from a pediatric diabetes clinic.
      Focus groups were used to elicit parent experiences and perceptions of diabetes
      management of their adolescents with type 2 diabetes. Questions concerning
      barriers to self-care behaviors were asked by trained group facilitators.
      Transcripts were coded into themes by three reviewers. Qualitative analyses were
      conducted using NVIVO software. RESULTS: Between 2003 and 2005, six focus groups
      were conducted with a total of 27 parents or guardians. Parents identified many
      barriers to and practical strategies for positive adolescent self-management.
      Five domains that influence self-management were identified: the role of others
      with diabetes, parenting skills, perceived lack of normalcy, environment, and
      adolescent development. Parents identified many barriers to dietary and exercise
      habits that were unique to the circumstances of adolescents with type 2 diabetes.
      CONCLUSIONS: Parents identified many barriers to self-management that may be
      unique to adolescents with type 2 diabetes. The importance of others and
      environmental influences in the self-management behavior of adolescents with type
      2 was evident. Interventions that are designed to improve self-management should
      include components that address multiple influences such as peers, school
      professionals, parents, siblings, and/or family systems.

PMID- 16644627
TI  - Blood glucose and coronary artery disease in nondiabetic patients.
AB  - OBJECTIVE: Nondiabetic patients were studied to determine whether modest
      elevations in blood glucose may be associated with a greater incidence of
      coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Baseline morning
      blood glucose determinations were evaluated with respect to subsequent coronary
      disease using records from 24,160 nondiabetic patients. CAD was identified from
      myocardial infarction, new diagnoses of angina, or new prescriptions for
      nitroglycerin that occurred more than a year after baseline glucose
      determinations. RESULTS: Of 24,160 patients studied, 3,282 patients developed CAD
      over a total analysis time at risk of 77,048 years. Higher baseline morning
      glucose (100-126 vs. <100 mg/dl) was associated with a 53.9% greater myocardial
      infarction incidence rate, an 18.6% greater acute coronary syndrome incidence
      rate, and a 26.4% greater number of new prescriptions for nitrates (all P <
      0.05). A Cox proportional hazards model with adjustment for age, BMI, sex,
      creatinine, lipids, smoking, and medications showed that elevated fasting glucose
      was associated with an increased hazard for new CAD (hazard ratio 1.13 [95% CI
      1.05-1.21], glucose >100 vs. <100 mg/dl). Kaplan-Meier analysis showed that
      elevated baseline glucose was associated with a progressive increase risk of CAD
      with time. CONCLUSIONS: Patients with higher baseline blood glucose levels in the
      absence of diabetes and after adjustment for covariants have a significantly
      greater risk for development of CAD.

PMID- 16644628
TI  - Mealtime interactions relate to dietary adherence and glycemic control in young
      children with type 1 diabetes.
AB  - OBJECTIVE: This study examined the relationships between parent-child mealtime
      interactions and dietary adherence and glycemic control in young children with
      type 1 diabetes. It was hypothesized that young children who exhibited disruptive
      mealtime behaviors would have more dietary deviations (poorer dietary adherence)
      and poor glycemic control. It was also hypothesized that parents of young
      children who used ineffective/coercive parenting strategies at mealtimes would
      have children with more dietary deviations and poor glycemic control. RESEARCH
      DESIGN AND METHODS: A total of 35 families of children (aged 2.2-7.9 years) with
      type 1 diabetes were recruited from a pediatric hospital. Families had at least
      three meals videotaped in their home, which were coded for parent, child, and
      eating behaviors, using the Dyadic Interaction Nomenclature for Eating.
      Children's dietary adherence was assessed according to deviations from the
      prescribed number of carbohydrate units per meal. Children's average glycemic
      excursion was assessed prospectively for 2 weeks, using a standardized home blood
      glucose meter. RESULTS: Findings demonstrated significant positive relationships
      between children's mealtime behavior, dietary deviations, and glycemic control.
      An examination of parent behaviors revealed significant positive correlations
      between parents' use of ineffective/coercive parenting strategies and children's
      dietary deviations and glycemic control. CONCLUSIONS: This was the first study to
      examine the relationship between parent-child mealtime interactions and health
      outcomes in young children with type 1 diabetes. The mealtime problems examined
      can be improved through specific behavioral interventions. Future research is
      needed to examine how parent-child interactions at mealtimes relate to children's
      health outcomes to inform clinical care.

PMID- 16644629
TI  - Diabetes as a tracer condition in international benchmarking of health systems.
AB  - OBJECTIVE: To assess the performance of health systems using diabetes as a tracer
      condition. RESEARCH DESIGN AND METHODS: We generated a measure of "case-fatality"
      among young people with diabetes using the mortality-to-incidence ratio (M/I
      ratio) for 29 industrialized countries using published data on diabetes incidence
      and mortality. Standardized incidence rates for ages 0-14 years were extracted
      from the World Health Organization DiaMond study for the period 1990-1994; data
      on death from diabetes for ages 0-39 years were obtained from the World Health
      Organization mortality database and converted into age-standardized death rates
      for the period 1994-1998, using the European standard population. RESULTS: The
      M/I ratio varied >10-fold. These relative differences appear similar to those
      observed in cohort studies of mortality among young people with type 1 diabetes
      in five countries. A sensitivity analysis showed that using plausible assumptions
      about potential overestimation of diabetes as a cause of death and
      underestimation of incidence rates in the U.S. yields an M/I ratio that would
      still be twice as high as in the U.K. or Canada. CONCLUSIONS: The M/I ratio for
      diabetes provides a means of differentiating countries on quality of care for
      people with diabetes. It is solely an indicator of potential problems, a basis
      for stimulating more detailed assessments of whether such problems exist, and
      what can be done to address them.

PMID- 16644630
TI  - The use of insulin pumps with meal bolus alarms in children with type 1 diabetes
      to improve glycemic control.
AB  - OBJECTIVE: The aim of this study was to determine whether the use of meal bolus
      alarms would result in fewer missed meal boluses per week in youth with type 1
      diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH
      DESIGN AND METHODS: This was a randomized trial of 48 youth using CSII, who were
      in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%. Twenty-four
      subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus
      alarms (experimental group), while the other 24 subjects continued use of their
      current insulin pumps (control group) without meal bolus alarms. RESULTS: After 3
      months of study, the number of missed meal boluses per week was significantly
      lower in the experimental group (from 4.9 +/- 3.7 to 2.5 +/- 2.5; P = 0.0005) but
      not significantly lower in the control group (from 4.3 +/- 2.7 to 4.2 +/- 3.9; P
      = 0.7610). Also after 3 months, the mean A1C value of the experimental group
      declined significantly (from 9.32 +/- 1.12 to 8.86 +/- 1.10; P = 0.0430). No
      significant decline in A1C was present for the control group (from 8.93 +/- 1.04
      to 8.67 +/- 1.17; P = 0.1940). After 6 months of study, the significant decline
      in A1C from baseline in the experimental group was no longer present. Pooling of
      all available data from the control and experimental groups showed that at
      baseline and 3 and 6 months, the number of missed meal boluses per week was
      significantly correlated with A1C values. CONCLUSIONS: While meal bolus alarms
      may have the potential to improve suboptimal glycemic control in youth using
      CSII, our results demonstrated that these alarms had only a transient, modest
      effect in doing so.

PMID- 16644631
TI  - Improvement of glycemic control, triglycerides, and HDL cholesterol levels with
      muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor
      activator, in patients with type 2 diabetes inadequately controlled with
      metformin monotherapy: A double-blind, randomized, pioglitazone-comparative
      study.
AB  - OBJECTIVE: We sought to evaluate the effects of muraglitazar, a dual
      (alpha/gamma) peroxisome proliferator-activated receptor (PPAR) activator within
      the new glitazar class, on hyperglycemia and lipid abnormalities. RESEARCH DESIGN
      AND METHODS: A double-blind, randomized, controlled trial was performed in 1,159
      patients with type 2 diabetes inadequately controlled with metformin. Patients
      received once-daily doses of either 5 mg muraglitazar or 30 mg pioglitazone for a
      total of 24 weeks in addition to open-label metformin. Patients were continued in
      a double-blind fashion for an additional 26 weeks. RESULTS: Analyses were
      conducted at week 24 for HbA1c (A1C) and at week 12 for lipid parameters. Mean
      A1C at baseline was 8.12 and 8.13% in muraglitazar and pioglitazone groups,
      respectively. At week 24, muraglitazar reduced mean A1C to 6.98% (-1.14% from
      baseline), and pioglitazone reduced mean A1C to 7.28% (-0.85% from baseline; P <
      0.0001, muraglitazar vs. pioglitazone). At week 12, muraglitazar and pioglitazone
      reduced mean plasma triglyceride (-28 vs. -14%), apolipoprotein B (-12 vs. -6%),
      and non-HDL cholesterol (-6 vs. -1%) and increased HDL cholesterol (19 vs. 14%),
      respectively (P < 0.0001 vs. pioglitazone for all comparisons). At week 24,
      weight gain (1.4 and 0.6 kg, respectively) and edema (9.2 and 7.2%, respectively)
      were observed in the muraglitazar and pioglitazone groups; at week 50, weight
      gain and edema were 2.5 and 1.5 kg, respectively, and 11.8 and 8.9%,
      respectively. At week 50, heart failure was reported in seven patients (five with
      muraglitazar and two with pioglitazone), and seven deaths occurred: three from
      sudden death, two from cerebrovascular accident, and one from pancreatic cancer
      in the muraglitazar group and one from perforated duodenal ulcer in the
      pioglitazone group. CONCLUSIONS: We found that 5 mg muraglitazar resulted in
      greater improvements in A1C and lipid parameters than a submaximal dose of 30 mg
      pioglitazone when added to metformin. Weight gain and edema were more common when
      muraglitazar was compared with a submaximal dose of pioglitazone.

PMID- 16644632
TI  - Monitoring kidney function in type 2 diabetic patients with incipient and overt
      diabetic nephropathy.
AB  - OBJECTIVE: The purpose of this study was to assess agreement between glomerular
      filtration rate (GFR) and the decline in GFR estimated with the Modification of
      Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula
      and measured by the plasma clearance of 51Cr-EDTA. RESEARCH DESIGN AND METHODS:
      We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years
      with four measurements of GFR and another cohort of 227 type 2 diabetic patients
      with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22)
      measurements of GFR. RESULTS: For patients with microalbuminuria, mean +/- SD
      baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103
      +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P <
      0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to
      30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2
      measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per
      1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with
      overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD
      equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault
      formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation)
      and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/-
      4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1)
      per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). CONCLUSIONS:
      Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly
      underestimated with wide limits of agreement by the MDRD equation as well as by
      the Cockcroft-Gault formula. The rate of decline in GFR is also significantly
      underestimated with both equations. This makes GFR estimations based upon these
      equations unacceptable for monitoring kidney function in type 2 diabetic patients
      with incipient and overt diabetic nephropathy.

PMID- 16644633
TI  - Increased plasma amylin in type 1 diabetic patients after kidney and pancreas
      transplantation: A sign of impaired beta-cell function?
AB  - OBJECTIVE: In response to hyperglycemia, beta-cells release insulin and C
      peptide, as well as islet amyloid pancreatic polypeptide, which is involved in
      glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type
      1 diabetic patients may revert to a nondiabetic metabolism without exogenous
      insulin therapy and re-secrete all beta-cell hormones. RESEARCH DESIGN AND
      METHODS: Using mathematical models, we investigated hormone (amylin, insulin, C
      peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell
      sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11
      nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2
      years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic
      patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3
      men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1
      kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance
      test (OGTT). RESULTS: PKT patients had higher fasting amylin (19 +/- 3 vs.
      control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10
      +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed
      increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In
      PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs.
      control subjects). Amylin clearance was comparable in all groups. Amylin's plasma
      concentrations and area under the concentration curve were up to twofold higher
      in PKT patients during OGTT (P < 0.05). OGIS was not significantly different
      between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (
      64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell
      sensitivity to glucose (r = -0.543, P < 0.004). CONCLUSIONS: After successful
      PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting
      and post-glucose load plasma amylin, which appears to be linked to impaired beta
      cell function. Thus, higher amylin release in proportion to insulin might also
      reflect impaired beta-cell function in type 1 diabetic patients after PKT.

PMID- 16644634
TI  - Effects of pioglitazone on endothelial function, insulin sensitivity, and glucose
      control in subjects with coronary artery disease and new-onset type 2 diabetes.
AB  - OBJECTIVE: About one of five patients with coronary artery disease (CAD) suffers
      from previously unknown, predominantly postprandial type 2 diabetes. In the
      process of atherogenesis and the subsequent increased cardiovascular mortality of
      diabetic patients, endothelial dysfunction is suspected to play an important
      role, and it is observed in diabetic as well as insulin-resistant states. Thus,
      the aim of our study was to investigate the effect of pioglitazone on endothelial
      dysfunction, insulin sensitivity, and glucose control in newly detected type 2
      diabetic patients with CAD. RESEARCH DESIGN AND METHODS: We investigated 42
      patients (39 men and 3 women, age 60.25 +/- 7.5 years, HbA1c 6.1 +/- 0.5%) with
      manifest CAD and newly detected type 2 diabetes. A randomized, double-blind,
      placebo-controlled, parallel study with pioglitazone (30 mg/day for 12 weeks) was
      performed. At study entry and end, we performed an oral glucose tolerance test
      and measurements of endothelial dysfunction by photoplethysmographic pulse wave
      analysis. RESULTS: Endothelial dysfunction was severely impaired at baseline in
      both groups. After 12 weeks, endothelial dysfunction was significantly better in
      the pioglitazone group (change of reflection index 6.5 +/- 5.1 vs. 1.6 +/- 2.9%,
      P = 0.002) compared with placebo. Insulin sensitivity, as assessed by homeostasis
      model assessment (2.20 +/- 1.62 vs. 3.61 +/- 1.87, P = 0.01), or the change of
      insulin sensitivity index from baseline to study end (0.021 +/- 0.023 vs. -0.003
      +/- 0.012 micromol x kg(-1) x min(-1) per pmol/l, P = 0.0001) and beta-cell
      function (57.42 +/- 49.86 vs. 21.78 +/- 18.54 mU/l per mmol/l, P = 0.0014)
      significantly improved in the pioglitazone group, with no change observed after
      placebo. CONCLUSIONS: Pioglitazone improves endothelial dysfunction independently
      from the observed benefits on insulin sensitivity and beta-cell function in
      patients with newly diagnosed type 2 diabetes and CAD.

PMID- 16644635
TI  - Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2
      Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian
      subjects: Evidence for heterogeneity.
AB  - OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor
      (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South
      Asians. RESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n =
      457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai,
      India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was
      determined using restriction fragment-length polymorphism. Insulin responsiveness
      to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects.
      RESULTS: The Caucasian diabetic subjects had significantly lower prevalence of
      PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs.
      9%, P = 0.006). However, there were no significant differences between diabetic
      and nondiabetic subjects with reference to the Pro12Ala polymorphism among the
      South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although
      Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of
      OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml,
      respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin
      concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala
      polymorphism and those with the wild-type genotype at either Chennai or Dallas.
      CONCLUSIONS: Although further replication studies are necessary to test the
      validity of the described genotype-phenotype relationship, our study supports the
      hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against
      diabetes in Caucasians but not in South Asians.

PMID- 16644636
TI  - The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated
      receptor-gamma2 gene on glucose/insulin metabolism interact with prenatal
      exposure to famine.
AB  - OBJECTIVE: An adverse fetal environment may permanently modify the effects of
      specific genes on glucose tolerance, insulin secretion, and insulin sensitivity.
      In the present study, we assessed a possible interaction of the peroxisome
      proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal
      exposure to famine on glucose and insulin metabolism. RESEARCH DESIGN AND
      METHODS: We measured plasma glucose and insulin concentrations after an oral
      glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term
      singletons born around the time of the 1944-1945 Dutch famine. RESULTS: A
      significant interaction effect between exposure to famine during midgestation and
      the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired
      glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was
      associated with a higher prevalence of impaired glucose tolerance and type 2
      diabetes but only in participants who had been prenatally exposed to famine
      during midgestation. Similar interactions were found for area under the curve for
      insulin and insulin increment ratio, which were lower for Ala carriers exposed to
      famine during midgestation. CONCLUSIONS: The effects of the PPAR-gamma2 Pro12Ala
      polymorphism on glucose and insulin metabolism may be modified by prenatal
      exposure to famine during midgestation. This is possibly due to a combined
      deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment
      and carrier type of the Ala allele in the PPAR-gamma2 gene.

PMID- 16644637
TI  - Burden of infection and insulin resistance in healthy middle-aged men.
AB  - OBJECTIVE: We hypothesized that burden of infection could be associated with
      chronic low-grade inflammation, resulting in insulin resistance. We aimed to
      study the effect of exposure to four infections on insulin sensitivity in
      apparently healthy middle-aged men (n = 124). RESEARCH DESIGN AND METHODS: By
      inclusion criteria, all subjects were hepatitis C virus antibody seronegative.
      Each study subject's serum was tested for specific IgG class antibodies against
      herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae
      through the use of quantitative in vitro enzyme-linked immunosorbent assays.
      Insulin sensitivity was evaluated using minimal model analysis. RESULTS: The HSV
      2 titer was negatively associated with insulin sensitivity even after controlling
      for BMI, age, and C-reactive protein (CRP). The associations were stronger when
      considering the infection burden. In particular, in those subjects who were
      seropositive for C. pneumoniae, the relationship between the quantitative
      seropositivity index (a measure of the exposure to various pathogens) and insulin
      sensitivity was strengthened (r = -0.50, P < 0.0001). We also observed decreasing
      mean insulin sensitivity index with increasing seropositivity score in subjects
      positive for enteroviruses. In the latter, the relationship between insulin
      sensitivity and seropositivity was especially significant (r = -0.71, P <
      0.0001). In a multivariate regression analysis, both BMI and quantitative
      seropositivity index (7%) independently predicted insulin sensitivity variance in
      subjects with C. pneumoniae seropositivity. When controlling for CRP, this
      association was no longer significant. CONCLUSIONS: Pathogen burden showed the
      strongest association with insulin resistance, especially with enteroviruses and
      C. pneumoniae seropositivity. We hypothesize that exposure to multiple pathogens
      could cause a chronic low-grade inflammation, resulting in insulin resistance.

PMID- 16644638
TI  - Antihypertensive medications and the risk of incident type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the association between the
      use of different classes of antihypertensive medications and the risk of incident
      type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective study of
      three cohorts: the Nurses' Health Study (NHS) I and II and the Health
      Professionals Follow-up Study (HPFS). Antihypertensive medication use was
      ascertained by biennial questionnaires. After excluding participants who reported
      a history of diabetes at baseline, 41,193 older women (NHS I), 14,151 younger
      women (NHS II), and 19,472 men (HPFS), all with hypertension, were followed for
      8, 10, and 16 years, respectively. RESULTS: We documented 3,589 incident cases of
      diabetes. After adjustment for age, BMI, physical activity, the use of other
      antihypertensive medications, and other risk factors, the multivariate relative
      risk (RR) of incident diabetes in participants taking a thiazide diuretic
      compared with those not taking a thiazide was 1.20 (95% CI 1.08-1.33) in older
      women, 1.45 (1.17-1.79) in younger women, and 1.36 (1.17-1.58) in men. The
      multivariate RR in participants taking a beta-blocker compared with those not
      taking a beta-blocker was 1.32 (1.20-1.46) in older women and 1.20 (1.05-1.38) in
      men. ACE inhibitors and calcium channel blockers were not associated with risk.
      CONCLUSIONS: Thiazide diuretic and beta-blocker use were independently associated
      with a higher risk of incident diabetes. Increased surveillance for diabetes in
      patients treated with these medications may be warranted.

PMID- 16644639
TI  - Effect of rosiglitazone on endothelial function and inflammatory markers in
      patients with the metabolic syndrome.
AB  - OBJECTIVE: The aim of this study was to assess the effect of rosiglitazone on
      endothelial function and inflammatory markers in patients with the metabolic
      syndrome. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind,
      controlled clinical trial. One hundred subjects (54 men and 46 women) with the
      metabolic syndrome, as defined by the Adult Treatment Panel III, were followed
      for 12 months after random assignment to rosiglitazone (4 mg/day) or placebo.
      Primary end points were flow-mediated dilation and high-sensitivity C-reactive
      protein (hs-CRP) levels; secondary end points were lipid and glucose parameters,
      homeostasis model assessment (HOMA) of insulin sensitivity, endothelial function
      score, and circulating levels of interleukin (IL)-6, IL-18, and adiponectin.
      RESULTS: Compared with 60 control subjects matched for age and sex, patients with
      the metabolic syndrome had decreased endothelial function, raised concentrations
      of inflammatory markers, and reduced insulin sensitivity. After 12 months,
      subjects with the metabolic syndrome receiving rosiglitazone showed improved flow
      mediated vasodilation (4.2%, P < 0.001) and reduced hs-CRP levels (-0.7 mg/dl, P
      = 0.04), compared with the placebo group. Moreover, HOMA (-0.8, P = 0.01) and
      serum concentrations of IL-6 (-0.5 pg/ml, P = 0.045) and IL-18 (-31 pg/ml, P =
      0.036) were significantly reduced in subjects receiving rosiglitazone, whereas
      adiponectin levels showed a significant increment (2.3 microg/ml, P = 0.02). High
      density lipoprotein-cholesterol levels increased more and triglyceride levels
      decreased more in the rosiglitazone group compared with the placebo group. At 1
      year of follow-up, 30 subjects receiving rosiglitazone still had features of the
      metabolic syndrome, compared with 45 subjects receiving placebo (P < 0.001).
      CONCLUSIONS: Rosiglitazone might be effective in reducing the prevalence of the
      metabolic syndrome.

PMID- 16644640
TI  - Association of elevated serum ferritin levels and the risk of gestational
      diabetes mellitus in pregnant women: The Camden study.
AB  - OBJECTIVE- We examined the influence of a moderately elevated serum ferritin
      level at entry to care on the risk of gestational diabetes mellitus (GDM) and a
      possible mechanism (increased iron stores versus inflammation). RESEARCH DESIGN
      AND METHODS- In a prospective observational study with 1,456 healthy pregnant
      women in Camden, New Jersey, serum ferritin and anthropometric measurements were
      determined. Serum C-reactive protein (CRP) concentration was measured in a nested
      case-control study of 172 subjects. RESULTS- Women who developed GDM had a higher
      concentration of serum ferritin than women who did not develop GDM (P < 0.001).
      Elevated serum ferritin level (highest quintile) was significantly and positively
      correlated with prepregnant BMI and skinfold measurements. Women in the highest
      quintile of serum ferritin had a twofold increased risk of developing GDM
      adjusted for several known risk factors (adjusted odds ratio, 2.02 [95% CI 1.04
      3.92], P < 0.05). Similar results were obtained with a nested case-control study,
      in which women in the highest tertile of serum ferritin (2.35 [1.06-5.22], P <
      0.05) or CRP (2.67 [1.16-6.17], P < 0.001) had a greater than twofold increased
      risk of GDM. However, these effects were modified and became nonstatistically
      significant after additional adjustment for prepregnant BMI. CONCLUSIONS-
      Elevated serum ferritin concentrations early in gestation are associated with an
      increased risk of GDM. The association, at least in part, is mediated by the
      maternal fat mass and obesity. These data suggest a possible link between
      elevated serum ferritin and low-grade inflammation.

PMID- 16644641
TI  - Metformin improves endothelial vascular reactivity in first-degree relatives of
      type 2 diabetic patients with metabolic syndrome and normal glucose tolerance.
AB  - OBJECTIVE: Endothelial dysfunction is an early marker of atherosclerosis seen in
      type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2
      diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We
      aimed to investigate the vascular effects of metformin in first-degree relatives
      with metabolic syndrome of type 2 diabetic patients. RESEARCH DESIGN AND METHODS:
      The study included 31 subjects (age 38.3 +/- 7.6 years and BMI 36.3 +/- 5.2
      kg/m2), who were first-degree relatives of type 2 diabetic patients and who had
      metabolic syndrome and normal glucose tolerance. The subjects were randomly
      assigned 1:1 in a double-blind fashion to receive placebo (n = 15) or metformin
      (n = 16). Endothelial function was assessed by venous occlusion plethysmography,
      measuring forearm blood flow (FBF) and vascular resistance responses to three
      intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30
      microg/min) and independent (sodium nitroprusside 2, 4, and 8 microg/min)
      vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and
      laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were
      assessed at baseline and after treatment. RESULTS: The metformin and placebo
      groups did not differ in anthropometric, clinical, laboratory, and vascular
      measurements at baseline. The metformin group had decreased weight, BMI, systolic
      blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF
      responses were also improved, without any effect on endothelium-independent
      responses. There was no correlation between the improvement on FBF responses and
      the observed changes on anthropometric, clinical, and laboratory parameters.
      CONCLUSIONS: We concluded that metformin improved vascular endothelial reactivity
      in first-degree relatives with metabolic syndrome of type 2 diabetic patients,
      independently of its known antihyperglycemic effects.

PMID- 16644642
TI  - Common presence of non-transferrin-bound iron among patients with type 2
      diabetes.
AB  - OBJECTIVE: Recently, we reported increased cardiovascular disease mortality among
      supplemental vitamin C users with type 2 diabetes in a prospective cohort study.
      Because vitamin C may cause oxidative stress in the presence of redox active
      iron, we hypothesized that non-transferrin-bound iron (NTBI), a form of iron
      susceptible to redox activity, may be present in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: We measured serum NTBI levels using high-performance
      liquid chromatography in 48 patients with known diabetes (at least 5 years
      duration since diagnosis), 49 patients with newly diagnosed diabetes, and 47
      healthy control subjects (frequency matched on age and sex). RESULTS: NTBI was
      commonly present in diabetes: 59% in newly diagnosed diabetes and 92% in advanced
      diabetes. Mean NTBI values varied significantly between the three groups, with
      the highest values being observed in patients with known diabetes and the lowest
      in the control subjects (0.62 +/- 0.43 vs. 0.24 +/- 0.29 vs. 0.04 +/- 0.13
      micromol/l Fe). Serum total iron or percent transferrin saturation were very
      similar among the three groups, yet NTBI was strongly associated with serum total
      iron (r = 0.74, P < 0.01) and percent transferrin saturation (r = 0.70, P < 0.01)
      among the patients with known diabetes. CONCLUSIONS: Consistent with our
      hypothesis, these data demonstrate the common existence of NTBI in type 2
      diabetic patients with a strong gradient with severity. Prospective cohort
      studies are required to clarify the clinical relevance of increased NTBI levels.

PMID- 16644643
TI  - Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic
      hepatitis C patients: A case-control study.
AB  - OBJECTIVE: The purpose of this study was to explore the initial pathogenic
      mechanisms of diabetes associated with hepatitis C virus (HCV) infection.
      RESEARCH DESIGN AND METHODS: Insulin resistance, proinflammatory cytokines, and
      beta-cell function were evaluated in a case-control study. A total of 28
      consecutive nondiabetic patients with chronic hepatitis C were included in the
      study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV
      infection served as the control group (anti-HCV-). Both groups were closely
      matched by the main clinical variables associated with insulin resistance and the
      degree of liver fibrosis. In addition, there were no differences between groups
      regarding hepatic insulin extraction measured by calculating the ratio between C
      peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis
      factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and
      interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin
      resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR])
      and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral
      glucose tolerance test, standard food intake, and intravenous glucagon) were
      determined by previously validated mathematic indexes. RESULTS: HOMA-IR was
      higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74;
      P = 0.01). All the proinflammatory cytokines analyzed were significantly higher
      in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2
      were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide
      responses after the intravenous glucagon test were significantly higher in anti
      HCV+ patients than in anti-HC- patients. CONCLUSIONS: Insulin resistance mediated
      by proinflammatory cytokines, but not a deficit in insulin secretion, could be
      the primary pathogenic mechanism involved in the development of diabetes
      associated with HCV infection.

PMID- 16644644
TI  - Is the association between dietary glycemic index and type 2 diabetes modified by
      waist circumference?

PMID- 16644645
TI  - Association of breast-feeding and early childhood overweight in children from
      mothers with gestational diabetes mellitus.

PMID- 16644646
TI  - Immune reactivity to a glb1 homologue in a highly wheat-sensitive patient with
      type 1 diabetes and celiac disease.

PMID- 16644647
TI  - Plasma sRAGE is independently associated with urinary albumin excretion in type 2
      diabetes.

PMID- 16644648
TI  - Is peripheral neuropathy associated with retinopathy and albuminuria in
      individuals with impaired glucose metabolism? The 1999-2000 AusDiab.

PMID- 16644649
TI  - Association of nephrin gene polymorphisms with type 2 diabetes in a Japanese
      population: The Funagata study.

PMID- 16644650
TI  - Contrasting testosterone concentrations in type 1 and type 2 diabetes.

PMID- 16644651
TI  - A proposal for the cutoff point of waist circumference for the diagnosis of
      metabolic syndrome in the Japanese population.

PMID- 16644652
TI  - Metabolic syndrome and risk of coronary, cerebral, and peripheral vascular
      disease in a large Dutch population with familial hypercholesterolemia.

PMID- 16644653
TI  - Incidence of type 2 diabetes in individuals with central obesity in a rural
      Japanese population: The Tanno and Sobetsu study.

PMID- 16644654
TI  - Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis
      of impaired glucose tolerance and impaired fasting glucose.
AB  - Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are
      intermediate states in glucose metabolism that exist between normal glucose
      tolerance and overt diabetes. Epidemiological studies demonstrate that the two
      categories describe distinct populations with only partial overlap, suggesting
      that different metabolic abnormalities characterize IGT and IFG. Insulin
      resistance and impaired beta-cell function, the primary defects observed in type
      2 diabetes, both can be detected in subjects with IGT and IFG. However, clinical
      studies suggest that the site of insulin resistance varies between the two
      disorders. While subjects with IGT have marked muscle insulin resistance with
      only mild hepatic insulin resistance, subjects with IFG have severe hepatic
      insulin resistance with normal or near-normal muscle insulin sensitivity. Both
      IFG and IGT are characterized by a reduction in early-phase insulin secretion,
      while subjects with IGT also have impaired late-phase insulin secretion. The
      distinct metabolic features present in subjects with IFG and IGT may require
      different therapeutic interventions to prevent their progression to type 2
      diabetes.

PMID- 16644655
TI  - Glucose abnormalities in patients with hepatitis C virus infection: Epidemiology
      and pathogenesis.

PMID- 16644656
TI  - Diabetic ketoacidosis in infants, children, and adolescents: A consensus
      statement from the American Diabetes Association.

PMID- 16644657
TI  - Cardiovascular disease.

PMID- 16644658
TI  - Antihypertensive therapy and the risk of new-onset diabetes.

PMID- 16644659
TI  - Point: impaired fasting glucose: The case for the new American Diabetes
      Association criterion.

PMID- 16644660
TI  - Counterpoint: impaired fasting glucose: The case against the new American
      Diabetes Association guidelines.

PMID- 16644661
TI  - The Biogun: A novel way of eradicating methicillin-resistant Staphylococcus
      aureus colonization in diabetic foot ulcers.

PMID- 16644662
TI  - Integrating pediatric diabetes education into routine clinical care: The
      Families, Adolescents and Children's Teamwork Study (FACTS).

PMID- 16644663
TI  - Prostatic cancer, hypogonadism, and insulin resistance: A case report.

PMID- 16644664
TI  - Retinopathy predicts future cardiovascular events among type 2 diabetic patients:
      The Valpolicella Heart Diabetes Study.

PMID- 16644665
TI  - A case of type 1 diabetes followed by methimazole-induced hypersensitivity
      syndrome.

PMID- 16644666
TI  - Favorable effects of early insulin secretion by nateglinide on postprandial
      hyperlipidemia in patients with type 2 diabetes.

PMID- 16644667
TI  - Association of hGrb10 genetic variations with type 2 diabetes in Caucasian
      subjects.

PMID- 16644668
TI  - Transient diabetes associated with withdrawal of lithium therapy.

PMID- 16644669
TI  - Change in HbA1c as a measure of quality of diabetes care.

PMID- 16644670
TI  - Metformin-induced pancreatitis: A possible adverse drug effect during acute renal
      failure.

PMID- 16644671
TI  - Glucose-dependent transcriptional regulation by an evolutionarily conserved
      glucose-sensing module.
AB  - We report here a novel mechanism for glucose-mediated activation of carbohydrate
      response element binding protein (ChREBP), a basic helix-loop-helix/leucine
      zipper (bHLH/ZIP) transcription factor of Mondo family that binds to carbohydrate
      response element in the promoter of some glucose-regulated genes and activates
      their expression upon glucose stimulation. Structure-function analysis of ChREBP
      in a highly glucose-sensitive system using GAL4-ChREBP fusion constructs revealed
      a glucose-sensing module (GSM) that mediates glucose responsiveness of ChREBP.
      GSM is conserved among Mondo family members; MondoA, a mammalian paralog of
      unknown function, and the GSM region of a Drosophila homolog were also found to
      be glucose responsive. GSM is composed of a low-glucose inhibitory domain (LID)
      and a glucose-response activation conserved element (GRACE). We have identified a
      new mechanism accounting for glucose responsiveness of ChREBP that involves
      specific inhibition of the transactivation activity of GRACE by LID under low
      glucose concentration and reversal of this inhibition by glucose in an
      orientation-sensitive manner. The intramolecular inhibition and its release by
      glucose is a regulatory mechanism that is independent of changes of subcellular
      localization or DNA binding activity, events that also appear to be involved in
      glucose responsiveness. This evolutionally conserved mechanism may play an
      essential role in glucose-responsive gene regulation.

PMID- 16644672
TI  - Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic
      beta-cell mass.
AB  - The glucoincretin hormone glucagon-like peptide-1 (GLP-1) increases pancreatic
      beta-cell proliferation and survival through sequential activation of the
      epidermal growth factor receptor (EGFR), phosphatidylinositol-3 kinase (PI 3
      kinase), and Akt. We investigated the role of transcription factor FoxO1 in the
      proliferative and antiapoptotic actions of GLP-1 in beta-cells. GLP-1 inhibited
      FoxO1 through phosphorylation-dependent nuclear exclusion in pancreatic beta
      (INS832/13) cells. The effect of GLP-1 was suppressed by inhibitors of EGFR
      (AG1478) and PI 3-kinase (LY294002). In contrast, LY294002 but not AG1478
      suppressed insulin-induced FoxO1 phosphorylation. Expression of constitutively
      nuclear FoxO1 in beta-cells prevented the proliferative and antiapoptotic actions
      of GLP-1 in cultured beta-cells and the increase in pancreatic beta-cell mass in
      response to Exendin4 in transgenic mice. Gene expression and chromatin
      immunoprecipitation assays demonstrated that GLP-1 increases pancreatic and
      duodenal homeobox gene-1 and Foxa2 expression and inhibits FoxO1 binding to both
      promoters. We propose that FoxO1 mediates the pleiotropic effects of the
      glucoincretin hormone on cell proliferation and survival.

PMID- 16644673
TI  - Impact of mitochondrial reactive oxygen species and apoptosis signal-regulating
      kinase 1 on insulin signaling.
AB  - Tumor necrosis factor (TNF)-alpha inhibits insulin action; however, the precise
      mechanisms are unknown. It was reported that TNF-alpha could increase
      mitochondrial reactive oxygen species (ROS) production, and apoptosis signal
      regulating kinase 1 (ASK1) was reported to be required for TNF-alpha-induced
      apoptosis. Here, we examined roles of mitochondrial ROS and ASK1 in TNF-alpha
      induced impaired insulin signaling in cultured human hepatoma (Huh7) cells. Using
      reduced MitoTracker Red probe, we confirmed that TNF-alpha increased
      mitochondrial ROS production, which was suppressed by overexpression of either
      uncoupling protein-1 (UCP)-1 or manganese superoxide dismutase (MnSOD). TNF-alpha
      significantly activated ASK1, increased serine phosphorylation of insulin
      receptor substrate (IRS)-1, and decreased insulin-stimulated tyrosine
      phosphorylation of IRS-1 and serine phosphorylation of Akt, and all of these
      effects were inhibited by overexpression of either UCP-1 or MnSOD. Similar to TNF
      alpha, overexpression of wild-type ASK1 increased serine phosphorylation of IRS-1
      and decreased insulin-stimulated tyrosine phosphorylation of IRS-1, whereas
      overexpression of dominant-negative ASK1 ameliorated these TNF-alpha-induced
      events. In addition, TNF-alpha activated c-jun NH(2)-terminal kinases (JNKs), and
      this observation was partially inhibited by overexpression of UCP-1, MnSOD, or
      dominant-negative ASK1. These results suggest that TNF-alpha increases
      mitochondrial ROS and activates ASK1 in Huh7 cells and that these TNF-alpha
      induced phenomena contribute, at least in part, to impaired insulin signaling.

PMID- 16644674
TI  - Mature-onset obesity in interleukin-1 receptor I knockout mice.
AB  - Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its
      biological activities through the IL-1 type I receptor (IL-1RI). The body weights
      of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice
      at 5-6 months of age and were 20% higher at 9 months of age. Visceral and
      subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic
      resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and
      crown-rump length were also slightly (11 and 5%, respectively) increased, as was
      serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by
      hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To
      elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(
      /-) mice were investigated. They showed decreased suppression of body weight and
      food intake in response to systemic leptin treatment. The decreased leptin
      responsiveness was even more pronounced in older obese animals. Moreover,
      spontaneous locomotor activity and fat utilization, as measured by respiratory
      quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL
      1RI-mediated biological activity causes mature-onset obesity. This obese
      phenotype is preceded by decreased leptin sensitivity, fat utilization, and
      locomotor activity.

PMID- 16644675
TI  - The class I HLA repertoire of pancreatic islets comprises the nonclassical class
      Ib antigen HLA-G.
AB  - Selective expression of the human class Ib HLA molecule HLA-G in immunologically
      protected sites and its function in the inhibition of NK and T-cell effector
      functions support an important role of this molecule in immunoregulation. Here,
      we demonstrate that HLA-G is constitutively expressed in the endocrine
      compartment of the human pancreas. Surface expression of this HLA determinant in
      endocrine cells is regulated in response to growth and inflammatory stimuli.
      Furthermore, we provide evidence that HLA-G expressed in this tissue may
      associate with a subset of insulin-containing granules and may be shuttled to the
      cell surface in response to secretory stimuli. Thus, HLA-G presentation by
      endocrine cells may be regulated in concert with their secretory activity. These
      results identify the expression of a major histocompatibility complex locus with
      putative regulatory functions in human pancreatic islets, a finding with
      potentially important implications for the progression of autoimmunity as well as
      for the establishment of transplant tolerance to this tissue.

PMID- 16644676
TI  - Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets.
AB  - The ubiquitin-proteasome pathway is crucial for protein turnover. Part of the
      pathway involves deubiquitination, which is carried out by cystein proteases
      known as ubiquitin COOH-terminal hydrolases. The isoform Uch-L1 was found to be
      present in large amounts in rat islets by immunostaining, Western blot analysis,
      and RT-PCR. Culturing islets in high glucose concentrations (16.7 mmol/l) for 24
      h led to decreased gene expression. Exposure to chronic hyperglycemia following
      90% partial pancreatectomy also led to reduced Uch-L1 expression. Expression of
      other members of the ubiquitin-proteasome pathway studied after culturing islets
      at high glucose concentrations revealed little change except for modest declines
      in parkin, human ubiquitin-conjugating enzyme 5 (UbcH5), and beta-TRCP
      (transducin repeat-containing protein). With the pancreatectomy model, expression
      of polyubiquitin-B and c-Cbl were increased and E6-associated protein was
      reduced. Further insight about the proteasome pathway was obtained with the
      proteasome inhibitor lactacystin, which in short-term 2-h experiments enhanced
      glucose-induced insulin secretion. An important role for the ubiquitin-proteasome
      pathways in beta-cells is suggested by the findings that changes in glucose
      concentration influence expression of genes in the pathway and that blockade of
      the proteasome degradation machinery enhances glucose-stimulated insulin
      secretion.

PMID- 16644677
TI  - 2-(8-hydroxy-6-methoxy-1-oxo-1h-2-benzopyran-3-yl) propionic acid, an inhibitor
      of angiogenesis, ameliorates renal alterations in obese type 2 diabetic mice.
AB  - One of the mechanisms involved in the progression of diabetic nephropathy, the
      most common cause of end-stage renal failure, is angiogenic phenomenon associated
      with the increase of angiogenic factors such as vascular endothelial growth
      factor (VEGF)-A and angiopoietin (Ang)-2, an antagonist of Ang-1. In the present
      study, we examined the therapeutic efficacy of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2
      benzopyran-3-yl) propionic acid (NM-3), a small molecule isocoumarin with
      antiangiogenic activity, using diabetic db/db mice, a model of obese type 2
      diabetes. Increases in kidney weight, glomerular volume, creatinine clearance,
      urinary albumin excretion, total mesangial fraction, glomerular type IV collagen,
      glomerular endothelial area (CD31(+)), and monocyte/macrophage accumulation
      (F4/80(+)) observed in control db/db mice were significantly suppressed by daily
      intraperitoneal injection of NM-3 (100 mg/kg, for 8 weeks). Increases in renal
      expression of VEGF-A, Ang-2, fibrogenic factor transforming growth factor (TGF)
      beta1, and chemokine monocyte chemoattractant protein-1 but not tumor necrosis
      factor-alpha were also inhibited by NM-3 in db/db mice. Furthermore, decreases of
      nephrin mRNA and protein levels in db/db mice were recovered by NM-3. In
      addition, treatment of db/db mice with NM-3 did not affect body weight, blood
      glucose, serum insulin, or food consumption. NM-3 significantly suppressed the
      increase of VEGF induced by high glucose in cultured podocytes and also
      suppressed the increase of VEGF and TGF-beta induced by high glucose in cultured
      mesangial cells. Taken together, these results demonstrate the potential use of
      NM-3 as a novel therapeutic agent for renal alterations in type 2 diabetes.

PMID- 16644678
TI  - Human vascular smooth muscle cells from diabetic patients are resistant to
      induced apoptosis due to high Bcl-2 expression.
AB  - An emerging body of evidence suggests that vascular remodeling in diabetic
      patients involves a perturbation of the balance between cell proliferation and
      cell death. Our aim was to study whether arteries and vascular smooth muscle
      cells (VSMCs) isolated from diabetic patients exhibit resistance to apoptosis
      induced by several stimuli. Internal mammary arteries (IMAs) were obtained from
      patients who had undergone coronary artery bypass graft surgery. Arteries from
      diabetic patients showed increasing levels of Bcl-2 expression in the media
      layer, measured by immunofluorescence and by Western blotting. Human IMA VSMCs
      from diabetic patients showed resistance to apoptosis, measured as DNA
      fragmentation and caspase-3 activation, induced by C-reactive protein (CRP) and
      other stimuli, such as hydrogen peroxide and 7beta-hydroxycholesterol. The
      diabetic cells also exhibited overexpression of Bcl-2. Knockdown of Bcl-2
      expression with Bcl-2 siRNA in cells from diabetic patients reversed the
      resistance to induced apoptosis. Consistent with the above, we found that
      pretreatment of nondiabetic VSMCs with high glucose abolished the degradation of
      Bcl-2 induced by CRP. Moreover, cell proliferation was increased in diabetic
      compared with nondiabetic cells. This differential effect was potentiated by
      glucose. We conclude that the data provide strong evidence that arterial
      remodeling in diabetic patients results from a combination of decreased apoptosis
      and increased proliferation.

PMID- 16644679
TI  - Diabetes-induced activation of canonical and noncanonical nuclear factor-kappaB
      pathways in renal cortex.
AB  - Evidence of diabetes-induced nuclear factor-kappaB (NF-kappaB) activation has
      been provided with DNA binding assays or nuclear localization with
      immunohistochemistry, but few studies have explored mechanisms involved. We
      examined effects of diabetes on proteins comprising NF-kappaB canonical and
      noncanonical activation pathways in the renal cortex of diabetic mice. Plasma
      concentrations of NF-kappaB-regulated cytokines were increased after 1 month of
      hyperglycemia, but most returned to control levels or lower by 3 months, when the
      same cytokines were increased significantly in renal cortex. Cytosolic content of
      NF-kappaB canonical pathway proteins did not differ between experimental groups
      after 3 months of diabetes, while NF-kappaB noncanonical pathway proteins were
      affected, including increased phosphorylation of inhibitor of kappaB kinase-alpha
      and several fold increases in NF-kappaB-inducing kinase and RelB, which were
      predominantly located in tubular epithelial cells. Nuclear content of all NF
      kappaB pathway proteins was decreased by diabetes, with the largest change in
      RelB and p50 (approximately twofold decrease). Despite this decrease, measurable
      increases in protein binding to DNA in diabetic versus control nuclear extracts
      were observed with electrophoretic mobility shift assay. These results provide
      evidence for chronic NF-kappaB activation in the renal cortex of db/db mice and
      suggest a novel, diabetes-linked mechanism involving both canonical and
      noncanonical NF-kappaB pathway proteins.

PMID- 16644680
TI  - Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type
      2 diabetes in the Japanese population.
AB  - Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor known as a key
      molecule in the development and functions of the beta-cells. In a previously
      performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed
      linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A
      gene is located. Recent studies have reported associations between type 2
      diabetes and polymorphisms in the P2 promoter region specific to beta-cells. In
      this study, we attempted to assess whether the HNF4A gene plays a role in the
      genetic susceptibility to type 2 diabetes in the Japanese population by analyzing
      polymorphisms and haplotypes of the HNF4A gene. Linkage disequilibrium across the
      P2 promoter region was preserved in the Japanese population, consistent with
      previous reports. Although none of the individual polymorphisms examined showed
      any significant association with type 2 diabetes, we found very strong evidence
      of the association between type 2 diabetes and the haplotype consisting of two
      polymorphisms in the P2 promoter region of the HNF4A gene (P = 3.82 x 10(-4)). In
      contrast, there was no association between type 2 diabetes and haplotypes
      consisting of polymorphisms not located in the P2 promoter region, suggesting
      that the type 2 diabetes susceptibility loci are localized in the P2 promoter
      region of the HNF4A gene. The association was replicated using two additional
      cohorts (P = 1.51 x 10(-4) and 0.019, respectively). The results of the present
      analysis revealed that the HNF4A gene might be a type 2 diabetes susceptibility
      gene common to different ethnic groups. The study also suggested the possible
      existence of an as-yet-unidentified but functional polymorphism in the P2
      promoter region of the HNF4A gene that directly influences susceptibility to type
      2 diabetes.

PMID- 16644681
TI  - Multi-SNP analysis of MHC region: remarkable conservation of HLA-A1-B8-DR3
      haplotype.
AB  - Technology has become available to cost-effectively analyze thousands of single
      nucleotide polymorphisms (SNPs). We recently confirmed by genotyping a small
      series of class I alleles and microsatellite markers that the extended haplotype
      HLA-A1-B8-DR3 (8.1 AH) at the major histocompatibility complex (MHC) is a common
      and conserved haplotype. To further evaluate the region of conservation of the
      DR3 haplotypes, we genotyped 31 8.1 AHs and 29 other DR3 haplotypes with a panel
      of 656 SNPs spanning 4.8 Mb in the MHC region. This multi-SNP evaluation revealed
      a 2.9-Mb region that was essentially invariable for all 31 8.1 AHs. The 31 8.1
      AHs were >99.9% identical for 384 consecutive SNPs of the 656 SNPs analyzed.
      Future association studies of MHC-linked susceptibility to type 1 diabetes will
      need to account for the extensive conservation of the 8.1 AH, since individuals
      who carry this haplotype provide no information about the differential effects of
      the alleles that are present on this haplotype.

PMID- 16644682
TI  - The ATGL gene is associated with free fatty acids, triglycerides, and type 2
      diabetes.
AB  - Adipose triglyceride lipase (ATGL) was recently described to predominantly
      perform the initial step in triglyceride hydrolysis and therefore seems to play a
      pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the
      first study investigating genetic variations within the ATGL gene in humans, 12
      polymorphisms identified via sequencing and database search were studied in 2,434
      individuals of European ancestry from Utah. These polymorphisms and their
      haplotypes were analyzed in subjects not taking diabetes medication for
      association with plasma free fatty acids (FFAs) as primary analysis, as well as
      triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190,
      respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an
      outcome. FFA concentrations were significantly associated with several single
      nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003),
      consistent with additive inheritance. The pattern was similar when considering
      triglyceride concentrations. Furthermore, two SNPs showed associations with
      glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype
      analysis supported and extended the shown SNP association analyses. These results
      complement previous findings of functional studies in mammals and elucidate a
      potential role of ATGL in pathways involved in components of the metabolic
      syndrome.

PMID- 16644683
TI  - Metabolic sensors mediate hypoglycemic detection at the portal vein.
AB  - The current study sought to ascertain whether portal vein glucose sensing is
      mediated by a metabolic fuel sensor analogous to other metabolic sensors presumed
      to mediate hypoglycemic detection (e.g., hypothalamic metabosensors). We examined
      the impact of selectively elevating portal vein concentrations of lactate,
      pyruvate, or beta-hydroxybutyrate (BHB) on the sympathoadrenal response to
      insulin-induced hypoglycemia. Male Wistar rats (n = 36), chronically cannulated
      in the carotid artery (sampling), jugular vein (infusion), and portal vein
      (infusion), underwent hyperinsulinemic-hypoglycemic ( approximately 2.5 mmol/l)
      clamps with either portal or jugular vein infusions of lactate, pyruvate, or BHB.
      By design, arterial concentrations of glucose and the selected metabolite were
      matched between portal and jugular (NS). Portal vein concentrations were
      significantly elevated in portal versus jugular (P < 0.0001) for lactate (5.03 +/
      0.2 vs. 0.84 +/- 0.08 mmol/l), pyruvate (1.81 +/- 0.21 vs. 0.42 +/- 0.03
      mmol/l), or BHB (2.02 +/- 0.1 vs. 0.16 +/- 0.03 mmol/l). Elevating portal lactate
      or pyruvate suppressed both the epinephrine (64% decrease; P < 0.01) and
      norepinephrine (75% decrease; P < 0.05) responses to hypoglycemia. In contrast,
      elevating portal BHB levels failed to impact epinephrine (P = 0.51) or
      norepinephrine (P = 0.47) levels during hypoglycemia. These findings indicate
      that hypoglycemic detection at the portal vein is mediated by a sensor responding
      to some metabolic event(s) subsequent to the uptake and oxidation of glucose.

PMID- 16644684
TI  - Insulin signaling and glucose transport in skeletal muscle from first-degree
      relatives of type 2 diabetic patients.
AB  - Aberrant insulin signaling and glucose metabolism in skeletal muscle from type 2
      diabetic patients may arise from genetic defects and an altered metabolic milieu.
      We determined insulin action on signal transduction and glucose transport in
      isolated vastus lateralis skeletal muscle from normal glucose-tolerant first
      degree relatives of type 2 diabetic patients (n = 8, 41 +/- 3 years, BMI 25.1 +/-
      0.8 kg/m(2)) and healthy control subjects (n = 9, 40 +/- 2 years, BMI 23.4 +/-
      0.7 kg/m(2)) with no family history of diabetes. Basal and submaximal insulin
      stimulated (0.6 and 1.2 nmol/l) glucose transport was comparable between groups,
      whereas the maximal response (120 nmol/l) was 38% lower (P < 0.05) in the
      relatives. Insulin increased phosphorylation of Akt and Akt substrate of 160 kDa
      (AS160) in a dose-dependent manner, with comparable responses between groups.
      AS160 phosphorylation and glucose transport were positively correlated in control
      subjects (R(2) = 0.97, P = 0.01) but not relatives (R(2) = 0.46, P = 0.32). mRNA
      of key transcriptional factors and coregulators of mitochondrial biogenesis were
      also determined. Skeletal muscle mRNA expression of peroxisome proliferator
      activated receptor (PPAR) gamma coactivator (PGC)-1alpha, PGC-1beta, PPARdelta,
      nuclear respiratory factor-1, and uncoupling protein-3 was comparable between
      first-degree relatives and control subjects. In conclusion, the uncoupling of
      insulin action on Akt/AS160 signaling and glucose transport implicates defective
      GLUT4 trafficking as an early event in the pathogenesis of type 2 diabetes.

PMID- 16644685
TI  - Methylglyoxal impairs the insulin signaling pathways independently of the
      formation of intracellular reactive oxygen species.
AB  - Nonenzymatic glycation is increased in diabetes and leads to elevated levels of
      advanced glycation end products (AGEs), which link hyperglycemia to the induction
      of insulin resistance. In hyperglycemic conditions, intracellularly formed alpha
      ketoaldehydes, such as methylglyoxal, are an essential source of intracellular
      AGEs, and the abnormal accumulation of methylglyoxal is related to the
      development of diabetes complications in various tissues and organs. We have
      previously shown in skeletal muscle that AGEs induce insulin resistance at the
      level of metabolic responses. Therefore, it was important to extend our work to
      intermediates of the biosynthetic pathway leading to AGEs. Hence, we asked the
      question whether the reactive alpha-ketoaldehyde methylglyoxal has deleterious
      effects on insulin action similar to AGEs. We analyzed the impact of
      methylglyoxal on insulin-induced signaling in L6 muscle cells. We demonstrate
      that a short exposure to methylglyoxal induces an inhibition of insulin
      stimulated phosphorylation of protein kinase B and extracellular-regulated kinase
      1/2, without affecting insulin receptor tyrosine phosphorylation. Importantly,
      these deleterious effects of methylglyoxal are independent of reactive oxygen
      species produced by methylglyoxal but appear to be the direct consequence of an
      impairment of insulin-induced insulin receptor substrate-1 tyrosine
      phosphorylation subsequent to the binding of methylglyoxal to these proteins. Our
      data suggest that an increase in intracellular methylglyoxal content hampers a
      key molecule, thereby leading to inhibition of insulin-induced signaling. By such
      a mechanism, methylglyoxal may not only induce the debilitating complications of
      diabetes but may also contribute to the pathophysiology of diabetes in general.

PMID- 16644686
TI  - Imaging of insulin signaling in skeletal muscle of living mice shows major role
      of T-tubules.
AB  - Insulin stimulates glucose transport in skeletal muscle by glucose transporter
      GLUT4 translocation to sarcolemma and membrane invaginations, the t-tubules.
      Although muscle glucose uptake plays a key role in insulin resistance and type 2
      diabetes, the dynamics of GLUT4 translocation and the signaling involved are not
      well described. We have now developed a confocal imaging technique to follow
      trafficking of green fluorescent protein-labeled proteins in living muscle fibers
      in situ in anesthetized mice. Using this technique, by imaging the dynamics of
      GLUT4 translocation and phosphatidylinositol 3,4,5 P(3) (PIP(3)) production in
      response to insulin, here, for the first time, we delineate the temporal and
      spatial distribution of these processes in a living animal. We find a 10-min
      delay of maximal GLUT4 recruitment and translocation to t-tubules compared with
      sarcolemma. Time-lapse imaging of a fluorescent dye after intravenous injection
      shows that this delay is similar to the time needed for insulin diffusion into
      the t-tubule system. Correspondingly, immunostaining of muscle fibers shows that
      insulin receptors are present throughout the t-tubule system. Finally, PIP(3)
      production, an early event in insulin signaling, progresses slowly along the t
      tubules with a 10-min delay between maximal PIP(3) production at sarcolemma
      compared with deep t-tubules following the appearance of dye-labeled insulin. Our
      findings in living mice indicate a major role of the t-tubules in insulin
      signaling in skeletal muscle and show a diffusion-associated delay in insulin
      action between sarcolemma and inner t-tubules.

PMID- 16644687
TI  - Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal
      for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin
      induced diabetic heart.
AB  - We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)
      dependent activation of Akt is essential for the expression of cardiac heat-shock
      protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)
      induced diabetic heart. STZ-induced male diabetic rats were treated with insulin
      (STZ-insulin group, n = 26) or vehicle (STZ-vehicle group, n = 61) for 3 weeks.
      Whole-body hyperthermia (43 degrees C for 20 min) was applied, and the heart was
      isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72
      expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart.
      Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and
      phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia
      treated STZ-vehicle heart showed poor left ventricular functional recovery during
      reperfusion after no-flow global ischemia compared with hyperthermia-treated
      control heart. Insulin treatment restored HSP72 expression and reperfusion
      induced functional recovery. In cultured neonatal rat cardiomyocytes,
      hyperthermia-induced HSP72 expression was enhanced by insulin, together with
      tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited
      hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results
      indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential
      for hyperthermia-induced HSP72 expression in association with cardioprotection,
      suggesting impairment of this signaling pathway in the STZ-induced diabetic
      heart, probably due to insulin deficiency.

PMID- 16644688
TI  - Intestinal insulin resistance and aberrant production of apolipoprotein B48
      lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia:
      evidence for activation of protein tyrosine phosphatase-1B, extracellular signal
      related kinase, and sterol regulatory element-binding protein-1c in the fructose
      fed hamster intestine.
AB  - Postprandial dyslipidemia is recognized as an important complication of insulin
      resistant states, and recent evidence implicates intestinal lipoprotein
      overproduction as a causative factor. The mechanisms linking intestinal
      lipoprotein overproduction and aberrant insulin signaling in intestinal
      enterocytes are currently unknown. Intestinal insulin sensitivity and lipid
      metabolism were studied in a fructose-fed hamster model of insulin resistance and
      metabolic dyslipidemia. Intestinal lipoprotein production in chow-fed hamsters
      was responsive to the inhibitory effects of insulin, and a decrease in
      circulating levels of triglyceride-rich apolipoprotein (apo)B48-containing
      lipoproteins occurred 60 min after insulin administration. However, fructose-fed
      hamster intestine was not responsive to the insulin-induced downregulation of
      apoB48-lipoprotein production, suggesting insulin insensitivity at the level of
      the intestine. Enterocytes from the fructose-fed hamster exhibited normal
      activity of the insulin receptor but reduced levels of insulin receptor substrate
      1 phosphorylation and mass and Akt protein mass. Conversely, the protein mass of
      the p110 subunit of phosphatidylinositol 3-kinase, protein tyrosine phosphatase
      1B, and basal levels of phosphorylated extracellular signal-related kinase (ERK)
      were significantly increased in the fructose-fed hamster intestine. Modulating
      the ERK pathway through in vivo inhibition of mitogen-activated protein/ERK
      kinase 1/2, the upstream activator of ERK1/2, we observed a significant decrease
      in intestinal apoB48 synthesis and secretion. Interestingly, enhanced basal ERK
      activity in the fructose-fed hamster intestine was accompanied by an increased
      activation of sterol regulatory element-binding protein. In summary, these data
      suggest that insulin insensitivity at the level of the intestine and aberrant
      insulin signaling are important underlying factors in intestinal overproduction
      of highly atherogenic apoB48-containing lipoproteins in the insulin-resistant
      state. Basal activation of the ERK pathway may be an important contributor to the
      aberrant insulin signaling and lipoprotein overproduction in this model.

PMID- 16644689
TI  - Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in
      the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA.
AB  - Fatty acid metabolism in the hypothalamus has recently been shown to regulate
      feeding. The selective estrogen receptor modulator tamoxifen (TMX) exerts a
      potent anorectic effect. Here, we show that the anorectic effect of TMX is
      associated with the accumulation of malonyl-CoA in the hypothalamus and
      inhibition of fatty acid synthase (FAS) expression specifically in the
      ventromedial nucleus of the hypothalamus (VMN). Furthermore, we demonstrate that
      FAS mRNA expression is physiologically regulated by fasting and refeeding in the
      VMN but not in other hypothalamic nuclei. Thus, the VMN appears to be the
      hypothalamic site where regulation of FAS and feeding converge. Supporting the
      potential clinical relevance of these observations, reanalysis of a primary
      breast cancer prevention study showed that obese women treated with TMX gained
      significantly less body weight over a 6-year period than obese women given
      placebo. The finding that TMX can modulate appetite through alterations in FAS
      expression and malonyl-CoA levels suggests a link between hypothalamic sex
      steroid receptors, fatty acid metabolism, and feeding behavior.

PMID- 16644690
TI  - Sex-discordant associations with adiponectin levels and lipid profiles in
      children.
AB  - In adults, lower circulating levels of the adipocyte-derived hormone adiponectin
      are associated with obesity, type 2 diabetes, and cardiovascular disease risks.
      Its use as a risk marker in children is less clear. In 839 children aged 8 years
      from a representative birth cohort, circulating adiponectin levels were
      associated with body weight, BMI, waist circumference, and fasting and 30-min
      insulin levels, but the associations were opposite in boys, with positive
      associations, and girls, with inverse associations (P = 0.008-0.00001 for
      interaction with sex). Girls had overall higher adiponectin, higher total
      cholesterol, lower HDL cholesterol, and higher triglyceride levels than boys,
      even after adjustment for BMI. With increasing BMI, girls showed steeper declines
      in HDL cholesterol (P = 0.01 for interaction) and adiponectin levels (P = 0.0005
      for interaction) and a steeper increase in triglyceride levels (P = 0.009 for
      interaction) compared with boys. In conclusion, plasma adiponectin is not a
      simple marker of central fat and insulin sensitivity in children. With increasing
      BMI, decreasing adiponectin levels in girls could contribute to their faster
      deterioration in lipid profiles in comparison with boys. Our data suggest a
      complex age- and sex-related regulation of adiponectin secretion or clearance.

PMID- 16644691
TI  - NFATc4 and ATF3 negatively regulate adiponectin gene expression in 3T3-L1
      adipocytes.
AB  - Expression of adiponectin decreases with obesity and insulin resistance. At
      present, the mechanisms responsible for negatively regulating adiponectin
      expression in adipocytes are poorly understood. In this investigation, we
      analyzed the effects of 5' serial deletion constructs on the murine adiponectin
      promoter. Here, we identified the repressor region located between -472 and -313
      bp of the promoter. Removal of the putative nuclear factor of activated T-cells
      (NFATs) binding site increased the promoter activity, and overexpression of
      NFATc4 reduced the promoter activity. Treatment with the calcium ionophore
      A23187, an activator of NFAT, reduced mRNA as well as promoter activity. The
      binding of NFATc4 to the promoter was associated with increased recruitment of
      histone deacetylase 1 and reduced acetylation of histone H3 at the promoter site.
      In addition, binding of activating transcription factor 3 (ATF3) to the putative
      activator protein-1 site located adjacent to the NFAT binding site also repressed
      the promoter activity. Treatment with thapsigargin, an inducer of ATF3, reduced
      both mRNA and promoter activity. Importantly, the binding activities of NFATc4
      and ATF3, increased significantly in white adipose tissues of ob/ob and db/db
      mice compared with controls. Taken together, this study demonstrates for the
      first time that NFATc4 and ATF3 function as negative regulators of adiponectin
      gene expression, which may play critical roles in downregulating adiponectin
      expression in obesity and type 2 diabetes.

PMID- 16644692
TI  - Regional differences in adipose tissue metabolism in women: minor effect of
      obesity and body fat distribution.
AB  - Studies comparing adipose tissue metabolism in central versus peripheral fat
      depots have generated equivocal data. We examined whether regional differences in
      abdominal subcutaneous and omental adipose tissue metabolism in women exist and
      whether they persist across the spectrum of body fatness and abdominal adiposity
      values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal,
      isoproterenol-, forskolin-, and dibutyryl cAMP-stimulated lipolysis in adipose
      tissue or mature adipocytes isolated from the omental and subcutaneous fat depots
      in a sample of 55 healthy women undergoing elective gynecological surgery.
      Measures of body fat mass and body fat distribution were also obtained by dual
      energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were
      significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed
      as a function of cell number was significantly higher in subcutaneous versus
      omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl
      cAMP-stimulated (10(-3) mol/l) and forskolin-stimulated (10(-5) mol/l) lipolysis
      (expressed as a function of cell number) were all significantly higher in
      subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the
      response of omental adipocytes to lipolytic stimuli tested (fold increase over
      basal level) was significantly greater in magnitude compared with subcutaneous
      adipocytes (P < 0.01). These differences were relatively constant across total
      body fat mass and visceral adipose tissue area tertiles. In conclusion, compared
      with adipocytes from the omental fat compartment, subcutaneous adipocytes are
      larger, have higher LPL activity, and are more lipolytic on an absolute basis,
      which may reflect a higher fat storage capacity in this depot in women. In
      contrast, omental adipocytes display greater relative responsiveness to both
      adrenergic receptor-and postreceptor-acting agents compared with subcutaneous
      adipocytes. Overall and visceral obesity have only minor effects on regional
      differences in adipose tissue metabolism.

PMID- 16644693
TI  - Effect of donor age on function of isolated human islets.
AB  - This study intended to evaluate the impact of donor age on the function of
      isolated islets. Analysis of human islets from cadaveric donors (age 16-70 years)
      was performed using glucose-stimulated insulin release (GSIR) (n = 93), islet ATP
      content (n = 27), diabetic nude mouse bioassay (n = 72), and the insulin
      secretory function after single-donor clinical islet allotransplantation (n = 7).
      The GSIR index was significantly higher in younger donors (age < or =40 years)
      than in older donors and negatively correlated with the donor age (r = -0.535).
      Islet ATP was higher in younger donors (115.7 +/- 17.7 vs. 75.7 +/- 6.6
      pmol/microg DNA). The diabetes reversal rate of mice with 2,000 IE was
      significantly higher in younger donors (96 vs. 68%). C-peptide increment to
      glucose during intravenous glucose tolerance test at days 90-120 after clinical
      transplantation showed negative correlation with donor age (r = -0.872) and
      positive correlation with the islet mass (r = 0.832). On the other hand, acute
      insulin response to arginine only showed correlation with the islet mass and not
      with donor age. These results show that insulin secretory response to glucose
      deteriorates with increasing age and that it may be related to changes in ATP
      generation in beta-cells.

PMID- 16644694
TI  - Activation of glucagon-like peptide-1 receptor signaling does not modify the
      growth or apoptosis of human pancreatic cancer cells.
AB  - Glucagon-like peptide (GLP)-1 promotes beta-cell proliferation and survival
      through stimulation of its specific G-protein-coupled receptor; however, the
      potential for GLP-1 receptor (GLP-1R) agonists to promote growth and
      proliferation of human pancreatic-derived cells remains poorly understood. We
      identified five human pancreatic cancer cell lines that express the GLP-1R and
      analyzed cell growth and survival in response to GLP-1R activation. Although
      cholera toxin (an activator of Galphas) and forskolin (an activator of adenylyl
      cyclase) increased levels of intracellular cAMP in all cell lines, the GLP-1R
      agonist exendin-4 (Ex-4) increased cAMP only in CFPAC-1 cells. Conversely, Ex-4
      induced extracellular regulated kinase (ERK) 1/2 activation in PL 45 cells in a
      GLP-1R-and epidermal growth factor receptor-dependent manner, whereas Ex-4
      inhibited ERK1/2 phosphorylation in Hs 766T and CAPAN-1 cells. Ex-4 did not
      modulate the proliferation of these cell lines in vitro and did not inhibit
      apoptosis after exposure of cells to cytotoxic agents such as cycloheximide,
      indomethacin, LY294002, or cyclopamine. Furthermore, daily Ex-4 treatment for 4
      weeks had no effect on the propagation of CFPAC-1 or PL 45 tumor cells evaluated
      in nude mice in vivo. Thus, acute or chronic (4 weeks) GLP-1R stimulation does
      not modify the growth or survival of human pancreatic cancer cells.

PMID- 16644695
TI  - Dexamethasone induces cell death in insulin-secreting cells, an effect reversed
      by exendin-4.
AB  - Glucocorticoid excess induces hyperglycemia, which may result in diabetes. The
      present experiments explored whether glucocorticoids trigger apoptosis in insulin
      secreting cells. Treatment of mouse beta-cells or INS-1 cells with the
      glucocorticoid dexamethasone (0.1 micromol/l) over 4 days in cell culture
      increased the number of fractionated nuclei from 2 to 7 and 14%, respectively, an
      effect that was reversed by the glucocorticoid receptor antagonist RU486 (1
      micromol/l). In INS-1 cells, dexamethasone increased the number of transferase
      mediated dUTP nick-end labeling-staining positive cells, caspase-3 activity, and
      poly-(ADP-) ribose polymerase protein cleavage; decreased Bcl-2 transcript and
      protein abundance; dephosphorylated the proapoptotic protein of the Bcl-2 family
      (BAD) at serine155; and depolarized mitochondria. Dexamethasone increased PP-2B
      (calcineurin) activity, an effect abrogated by FK506. FK506 (0.1 micromol/l) and
      another calcineurin inhibitor, deltamethrin (1 micromol/l), attenuated
      dexamethasone-induced cell death. The stable glucagon-like peptide 1 analog,
      exendin-4 (10 nmol/l), inhibited dexamethasone-induced apoptosis in mouse beta
      cells and INS-1 cells. The protective effect of exendin-4 was mimicked by
      forskolin (10 micromol/l) but not mimicked by guanine nucleotide exchange factor
      with the specific agonist 8CPT-Me-cAMP (50 micromol/l). Exendin-4 did not protect
      against cell death in the presence of cAMP-dependent protein kinase (PKA)
      inhibition by H89 (10 micromol/l) or KT5720 (5 micromol/l). In conclusion,
      glucocorticoid-induced apoptosis in insulin-secreting cells is accompanied by a
      downregulation of Bcl-2, activation of calcineurin with subsequent
      dephosphorylation of BAD, and mitochondrial depolarization. Exendin-4 protects
      against glucocorticoid-induced apoptosis, an effect mimicked by forskolin and
      reversed by PKA inhibitors.

PMID- 16644696
TI  - L-cysteine inhibits insulin release from the pancreatic beta-cell: possible
      involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter.
AB  - Hydrogen sulfide (H(2)S) was historically recognized as a toxic gas generated by
      natural resources. However, its enzymatic production from L-cysteine has recently
      been demonstrated in mammals. Cystathionine beta-synthase and cystathionine gamma
      lyase, both of which can produce H(2)S, were expressed in mouse pancreatic islet
      cells and the beta-cell line, MIN6. L-cysteine and the H(2)S donor NaHS inhibited
      glucose-induced insulin release from islets and MIN6 cells. These inhibitory
      effects were reproduced when insulin release was stimulated by alpha
      ketoisocaproate, tolbutamide, or high K+. L-cysteine and NaHS inhibited glucose
      potentiated insulin release in the copresence of diazoxide and high K+. Real-time
      imaging of intracellular Ca2+ concentration ([Ca2+](i)) demonstrated that both L
      cysteine and NaHS reversibly suppressed glucose-induced [Ca2+](i) oscillation in
      a single beta-cell without obvious changes in the mean value. These substances
      inhibited Ca2+ - or guanosine 5'-0-3-thiotriphosphate-induced insulin release
      from islets permeabilized with streptolysin-O. L-cysteine and NaHS reduced ATP
      production and attenuated glucose-induced hyperpolarization of the mitochondrial
      membrane potential. Finally, L-cysteine increased H(2)S content in MIN6 cells. We
      suggest here that L-cysteine inhibits insulin release via multiple actions on the
      insulin secretory process through H(2)S production. Because the activities of
      H(2)S-producing enzymes and the tissue H(2)S contents are known to increase under
      diabetic conditions, the inhibition may participate in the deterioration of
      insulin release in this disease.

PMID- 16644697
TI  - Pro- and antiapoptotic proteins regulate apoptosis but do not protect against
      cytokine-mediated cytotoxicity in rat islets and beta-cell lines.
AB  - Type 1 diabetes results from islet beta-cell death and dysfunction induced by an
      autoimmune mechanism. Proinflammatory cytokines such as interleukin-1beta and
      gamma-interferon are mediators of this beta-cell cytotoxicity, but the mechanism
      by which damage occurs is not well understood. In the current study, we present
      multiple lines of evidence supporting the conclusion that cytokine-induced
      killing of rat beta-cells occurs predominantly by a nonapoptotic mechanism,
      including the following: 1) A rat beta-cell line selected for resistance to
      cytokine-induced cytotoxicity (833/15) is equally sensitive to killing by the
      apoptosis-inducing agents camptothecin and etoposide as a cytokine-sensitive cell
      line (832/13). 2) Overexpression of a constitutively active form of the
      antiapoptotic protein kinase Akt1 in 832/13 cells provides significant protection
      against cell killing induced by camptothecin and etoposide but no protection
      against cytokine-mediated damage. 3) Small interfering RNA-mediated suppression
      of the proapoptotic protein Bax enhances viability of 832/13 cells upon exposure
      to the known apoptosis-inducing drugs but not the inflammatory cytokines. 4)
      Exposure of primary rat islets or 832/13 cells to the inflammatory cytokines
      causes cell death as evidenced by the release of adenylate kinase activity into
      the cell medium, with no attendant increase in caspase 3 activation or annexin V
      staining. In contrast, camptothecin- and etoposide-induced killing is associated
      with robust increases in caspase 3 activation and annexin V staining. 5)
      Camptothecin increases cellular ATP levels, whereas inflammatory cytokines lower
      ATP levels in both beta-cell lines and primary islets. We conclude that
      proinflammatory cytokines cause beta-cell cytotoxicity primarily through a
      nonapoptotic mechanism linked to a decline in ATP levels.

PMID- 16644698
TI  - Complete protection against interleukin-1beta-induced functional suppression and
      cytokine-mediated cytotoxicity in rat pancreatic islets in vitro using an
      interleukin-1 cytokine trap.
AB  - Cytokines, particularly interleukin (IL)-1beta, have been postulated to cause
      beta-cell destruction in type 1 diabetes. We tested the efficacy of an IL-1
      cytokine trap in counteraction of suppressive and toxic effects after exposure of
      rat pancreatic islets in vitro to IL-1beta. The IL-1 cytokine trap used herein
      comprised extracellular domains of the IL-1 receptor accessory protein and the
      human IL-1 receptor 1 arranged inline and fused to the Fc portion of human IgG1.
      Groups of isolated rat pancreatic islets were maintained in medium culture with
      or without IL-1beta (150 pmol/l) for 48 hours in the absence or presence of the
      IL-1 trap at 1-, 10-, or 100-fold excess the molar concentration of the cytokine.
      IL-1beta alone induced a strong inhibition of insulin secretion and glucose
      oxidation rate and a marked increase in medium nitrite accumulation as an
      indicator of nitric oxide generation. When the IL-1 trap was used at a ratio 10:1
      or 100:1, a complete protection against these effects were observed. Moreover,
      the IL-1 trap (100:1) blocked the increased islet cell death seen in islets
      treated with a combination of IL-1beta + tumor necrosis factor-alpha + interferon
      gamma as well as functional suppression induced by the cytokine combination. In
      conclusion, we show that addition of an IL-1 trap can protect rat pancreatic
      islets in vitro against noxious effects induced by IL-1beta. Exploring the IL-1
      trap in relevant animal models of type 1 diabetes represents an interesting
      future intervention strategy.

PMID- 16644699
TI  - Blockade of beta1 integrin-laminin-5 interaction affects spreading and insulin
      secretion of rat beta-cells attached on extracellular matrix.
AB  - When attached on a matrix produced by a rat bladder carcinoma cell line (804G
      matrix), rat pancreatic beta-cells spread in response to glucose and secrete more
      insulin compared with cells attached on poly-l-lysine. The aim of this study was
      to determine whether laminin-5 and its corresponding cell receptor beta1 integrin
      are implicated in these phenomena. By using specific blocking antibodies, we
      demonstrated that laminin-5 is the component present in 804G matrix responsible
      for the effect of 804G matrix on beta-cell function and spreading. When
      expression of two well-known laminin-5 ligands, beta1 and beta4 integrin, was
      assessed by Western blot and RT-PCR, only the beta1 integrin was detected in beta
      cells. Anti-beta1 integrin antibody reduced the spreading of beta-cells on 804G
      matrix. Blockade of the interaction between beta1 integrins and laminin-5
      resulted in a reduction in glucose-stimulated insulin secretion. Blocking anti
      beta1 integrin antibody also inhibited focal adhesion kinase phosphorylation
      induced by 804G matrix. In conclusion, anti-beta1 integrin and -laminin-5
      antibodies interfere with spreading of beta-cells, resulting in decreased insulin
      secretion in response to glucose. Our findings indicate that outside-in signaling
      via engagement of beta1 integrins by laminin-5 is an important component of
      normal beta-cell function.

PMID- 16644700
TI  - Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose
      tolerance.
AB  - Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic
      vesicle priming. We recently showed that Munc13-1 is expressed in rodent and
      human islet beta-cells and that its levels are reduced in islets of type 2
      diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes
      to the abnormal insulin secretion in diabetes. To unequivocally demonstrate the
      role of Munc13-1 in insulin secretion, we studied heterozygous Munc13-1 knockout
      mice (+/-), which exhibited elevated glucose levels during intraperitoneal
      glucose tolerance tests with corresponding lower serum insulin levels. Munc13
      1(+/-) mice exhibited normal insulin tolerance, indicating that a primary islet
      beta-cell secretory defect is the major cause of their hyperglycemia.
      Consistently, glucose-stimulated insulin secretion was reduced 50% in isolated
      Munc13-1(+/-) islets and was only partially rescued by phorbol ester
      potentiation. The corresponding alterations were minor in mice expressing one
      allele of a Munc13-1 mutant variant, which does not bind DAG (H567K/+).
      Capacitance measurements of Munc13-1(+/-) and Munc13-1(H567k/+) islet beta-cells
      revealed defects in granule priming, including the initial size and refilling of
      the releasable pools, which become accentuated by phorbol ester potentiation. We
      conclude that Munc13-1 plays an important role in glucose-stimulated insulin
      secretion and that Munc13-1 deficiency in the pancreatic islets as occurs in
      diabetes can reduce insulin secretion sufficient to cause abnormal glucose
      homeostasis.

PMID- 16644701
TI  - Insulin secretion and action in subjects with impaired fasting glucose and
      impaired glucose tolerance: results from the Veterans Administration Genetic
      Epidemiology Study.
AB  - This study was conducted to observe changes in insulin secretion and insulin
      action in subjects with impaired fasting glucose (IFG) and/or impaired glucose
      tolerance (IGT). A total of 319 subjects were studied with an oral glucose
      tolerance test (OGTT). Fasting plasma glucose and insulin concentrations were
      measured at baseline and every 30 min during the OGTT. Fifty-eight subjects also
      received a euglycemic-hyperinsulinemic clamp. Insulin sensitivity was calculated
      as the total glucose disposal (TGD) during the last 30 min of the clamp.
      Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from
      fasting plasma glucose and insulin concentrations. Subjects with IFG had TGD
      similar to normal glucose-tolerant subjects, while subjects with IGT and combined
      IFG/IGT had significantly reduced TGD. HOMA-IR in subjects with IFG was similar
      to that in subjects with combined IFG/IGT and significantly higher than HOMA-IR
      in subjects with IGT or NGT. Insulin secretion, measured by the insulinogenic
      index (DeltaI(0-30)/DeltaG(0-30)) and by the ratio of the incremental area under
      the curve (AUC) of insulin to the incremental AUC of glucose (0-120 min), was
      reduced to the same extent in all three glucose-intolerant groups. When both
      measurements of beta-cell function were adjusted for severity of insulin
      resistance, subjects with IGT and combined IFG/IGT had a significantly greater
      reduction in insulin secretion than subjects with IFG. Subjects with IGT and IFG
      have different metabolic characteristics. Differences in insulin sensitivity and
      insulin secretion may predict different rates of progression to type 2 diabetes
      and varying susceptibility to cardiovascular disease.

PMID- 16644702
TI  - Obesity blunts insulin-mediated microvascular recruitment in human forearm
      muscle.
AB  - We have previously shown that skeletal muscle capillaries are rapidly recruited
      by physiological doses of insulin in both humans and animals. This facilitates
      glucose and insulin delivery to muscle, thus augmenting glucose uptake. In obese
      rats, both insulin-mediated microvascular recruitment and glucose uptake are
      diminished; however, this action of insulin has not been studied in obese humans.
      Here we used contrast ultrasound to measure microvascular blood volume (MBV) (an
      index of microvascular recruitment) in the forearm flexor muscles of lean and
      obese adults before and after a 120-min euglycemic-hyperinsulinemic (1 mU . min(
      1) . kg(-1)) clamp. We also measured brachial artery flow, fasting lipid profile,
      and anthropomorphic variables. Fasting plasma glucose (5.4 +/- 0.1 vs. 5.1 +/-
      0.1 mmol/l, P = 0.05), insulin (79 +/- 11 vs. 38 +/- 6 pmol/l, P = 0.003), and
      percent body fat (44 +/- 2 vs. 25 +/- 2%, P = 0.001) were higher in the obese
      than the lean adults. After 2 h of insulin infusion, whole-body glucose infusion
      rate was significantly lower in the obese versus lean group (19.3 +/- 3.2 and
      37.4 +/- 2.6 mumol . min(-1) . kg(-1) respectively, P < 0.001). Compared with
      baseline, insulin increased MBV in the lean (18.7 +/- 3.3 to 25.0 +/- 4.1, P =
      0.019) but not in the obese group (20.4 +/- 3.6 to 18.8 +/- 3.8, NS). Insulin
      increased brachial artery diameter and flow in the lean but not in the obese
      group. We observed a significant, negative correlation between DeltaMBV and BMI
      (R = -0.482, P = 0.027) in response to insulin. In conclusion, obesity eliminated
      the insulin-stimulated muscle microvascular recruitment and increased brachial
      artery blood flow seen in lean individuals.

PMID- 16644703
TI  - Zonulin upregulation is associated with increased gut permeability in subjects
      with type 1 diabetes and their relatives.
AB  - Zonulin, a protein that modulates intestinal permeability, is upregulated in
      several autoimmune diseases and is involved in the pathogenesis of autoimmune
      diabetes in the BB/Wor animal model of the disease. To verify the association
      between serum zonulin levels and in vivo intestinal permeability in patients with
      type 1 diabetes, both parameters were investigated in different stages of the
      autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal
      serum zonulin levels, as compared with age-matched control subjects. The
      increased zonulin levels correlated with increased intestinal permeability in
      vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while
      no changes were detected in ZO1 and occludin genes expression. When tested in
      serum samples collected during the pre-type 1 diabetes phase, elevated serum
      zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the
      onset of the disease in those patients who went on to develop type 1 diabetes.
      Combined, these results suggest that zonulin upregulation is associated with
      increased intestinal permeability in a subgroup of type 1 diabetic patients.
      Zonulin upregulation seems to precede the onset of the disease, providing a
      possible link between increased intestinal permeability, environmental exposure
      to non-self antigens, and the development of autoimmunity in genetically
      susceptible individuals.

PMID- 16644704
TI  - Elevated activity of transcription factor nuclear factor of activated T-cells 5
      (NFAT5) and diabetic nephropathy.
AB  - The expression of aldose reductase is tightly regulated by the transcription
      factor tonicity response element binding protein (TonEBP/NFAT5) binding to three
      osmotic response elements (OREs; OREA, OREB, and OREC) in the gene. The aim was
      to investigate the contribution of NFAT5 to the pathogenesis of diabetic
      nephropathy. Peripheral blood mononuclear cells (PBMCs) were isolated from the
      following subjects: 44 Caucasoid patients with type 1 diabetes, of whom 26 had
      nephropathy and 18 had no nephropathy after a diabetes duration of 20 years, and
      13 normal healthy control subjects. In addition, human mesangial cells (HMCs)
      were isolated from the normal lobe of 10 kidneys following radical nephrectomy
      for renal cell carcinoma. Nuclear and cytoplasmic proteins were extracted from
      PBMCs and HMCs and cultured in either normal or high-glucose (31 mmol/l D
      glucose) conditions for 5 days. NFAT5 binding activity was quantitated using
      electrophoretic mobility shift assays for each of the OREs. Western blotting was
      used to measure aldose reductase and sorbitol dehydrogenase protein levels. There
      were significant fold increases in DNA binding activities of NFAT5 to OREB (2.06
      +/- 0.03 vs. 1.33 +/- 0.18, P = 0.033) and OREC (1.94 +/- 0.21 vs. 1.39 +/- 0.11,
      P = 0.024) in PBMCs from patients with diabetic nephropathy compared with
      diabetic control subjects cultured under high glucose. Aldose reductase and
      sorbitol dehydrogenase protein levels in the patients with diabetic nephropathy
      were significantly increased in PBMCs cultured in high-glucose conditions. In
      HMCs cultured under high glucose, there were significant increases in NFAT5
      binding activities to OREA, OREB, and OREC by 1.38 +/- 0.22-, 1.84 +/- 0.44-, and
      2.38 +/- 1.15-fold, respectively. Similar results were found in HMCs exposed to
      high glucose (aldose reductase 1.30 +/- 0.06-fold and sorbitol dehydrogenease
      1.54 +/- 0.24-fold increases). Finally, the silencing of the NFAT5 gene in vitro
      reduced the expression of the aldose reductase gene. In conclusion, these results
      show that aldose reductase is upregulated by the transcriptional factor NFAT5
      under high-glucose conditions in both PBMCs and HMCs.

PMID- 16644705
TI  - Insulin resistance and microalbuminuria: a cross-sectional, case-control study of
      158 patients with type 2 diabetes and different degrees of urinary albumin
      excretion.
AB  - Microalbuminuria is a risk factor for renal and cardiovascular disease. A role
      for insulin resistance in the pathogenesis of microalbuminuria has been suggested
      but is still unproven. In this case-control, cross-sectional study, we compared
      glucose disposal rate (GDR), measured by hyperinsulinemic-euglycemic clamp, in 50
      pairs of matched type 2 diabetic patients with micro- or normoalbuminuria (main
      study) and in 29 matched pairs of diabetic patients with macro- or
      microalbuminuria (substudy). In the main study, GDR was approximately 25% lower
      in micro- than in normoalbuminuric patients (5.20 +/- 1.91 vs. 6.86 +/- 2.88 mg .
      kg(-1) . min(-1), P < 0.05) and was independently associated with
      microalbuminuria (P = 0.002), with each 1 mg . kg(-1) . min(-1) decrease
      predicting approximately 40% increased prevalence (odds ratio 1.37 [95% CI 1.14
      1.70]). Microalbuminuria was threefold more frequent in patients with GDR < or
      =7.50 +/- 2.56 mg . kg(-1) . min(-1) than in those with higher GDR (60% vs. 20%,
      P < 0.005). In the substudy, GDR in macro- and microalbuminuric patients was
      comparable (5.52 +/- 2.56 vs. 5.16 +/- 1.61 mg . kg(-1) . min(-1)) and
      independent of macroalbuminuria. GDR was significantly correlated with urinary
      albumin excretion rate in the main study (P = 0.004) but not in the substudy (P =
      0.60). In type 2 diabetes, more severe insulin resistance is independently
      associated with microalbuminuria. Longitudinal studies are needed to clarify the
      role of insulin resistance in the pathogenesis of microalbuminuria and related
      complications.

PMID- 16644706
TI  - The 30-year natural history of type 1 diabetes complications: the Pittsburgh
      Epidemiology of Diabetes Complications Study experience.
AB  - Declining incidences in Europe of overt nephropathy, proliferative retinopathy,
      and mortality in type 1 diabetes have recently been reported. However, comparable
      data for the U.S. and trend data for neuropathy and macrovascular complications
      are lacking. These issues are addressed using the prospective observational
      Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study.
      Participants were stratified into five cohorts by diagnosis year: 1950-1959, 1960
      1964, 1965-1969, 1970-1974, and 1975-1980. Mortality, renal failure, and coronary
      artery disease (CAD) status were determined on the complete cohort (n = 906) at
      20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and
      neuropathy were assessed at 20 and 25 years on the subset of participants with a
      clinical examination. There was a decreasing trend by diagnosis year for
      mortality, renal failure, and neuropathy across all time intervals (P < 0.05),
      with the 1950-1959 cohort having a fivefold higher mortality at 25 years than the
      1970s' cohorts. Proliferative retinopathy and overt nephropathy showed
      nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no
      change at 25 years. CAD event rates, which were lower than the other
      complications, also showed no trend. Although some type 1 diabetes complications
      (mortality, renal failure, and neuropathy) are declining, others (CAD, overt
      nephropathy, and proliferative retinopathy) show less favorable changes by 30
      years.

PMID- 16644707
TI  - Effects of basic fibroblast growth factor on experimental diabetic neuropathy in
      rats.
AB  - Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural
      cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in
      streptozotocin-induced diabetic rats. Diabetic rats were treated with human
      recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular
      injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH),
      and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve
      conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity
      to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow
      (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves,
      hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by
      intravenous administration of bFGF after 10, but not 30, days. Intramuscular
      injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and
      SNBF after 10 and 30 days, but caudal MNCV was not improved. However,
      intramuscular injection of bFGF with saline had no significant effects. bFGF did
      not significantly alter RBF in either normal or diabetic rats. These observations
      suggest that bFGF could have therapeutic value for diabetic neuropathy and that
      CGH could play important roles as a carrier of bFGF.

PMID- 16644708
TI  - Aldose reductase pathway inhibition improved vascular and C-fiber functions,
      allowing for pressure-induced vasodilation restoration during severe diabetic
      neuropathy.
AB  - Pressure-induced vasodilation, a neurovascular mechanism relying on the
      interaction between mechanosensitive C-fibers and vessels, allows skin blood flow
      to increase in response to locally nonnociceptive applied pressure that in turn
      may protect against pressure ulcers. We expected that severe neuropathy would
      dramatically affect pressure-induced vasodilation in diabetic mice, and we aimed
      to determine whether pressure-induced vasodilation alteration could be reversed
      in 8-week diabetic mice. Control and diabetic mice received no treatment or
      sorbinil, an aldose reductase inhibitor, or alagebrium, an advanced glycation end
      product breaker, the last 2 weeks of diabetes. Laser Doppler flowmetry was used
      to evaluate pressure-induced vasodilation and endothelium-dependent vasodilation
      after iontophoretic delivery of acetylcholine (ACh). We assessed the nervous
      function with measurements of motor nerve conduction velocity (MNCV) as well as
      the C-fiber-mediated nociception threshold. Pressure-induced vasodilation,
      endothelial response, C-fiber threshold, and MNCV were all altered in 8-week
      diabetic mice. None of the treatments had a significant effect on MNCV. Although
      sorbinil and alagebrium both restored ACh-dependent vasodilation, sorbinil was
      the sole treatment to restore the C-fiber threshold as well as pressure-induced
      vasodilation development. Therefore, the inhibition of aldose reductase pathway
      by sorbinil improved vascular and C-fiber functions that allow pressure-induced
      vasodilation restoration that could limit neuropathic diabetic cutaneous pressure
      ulcers.

PMID- 16644709
TI  - Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose
      requires a functional glucagon-like peptide 1 receptor.
AB  - Nondigestible fermentable dietary fibers such as oligofructose (OFS) exert an
      antidiabetic effect and increase the secretion of glucagon-like peptide 1 (GLP
      1). To determine the importance of GLP-1 receptor-dependent mechanisms for the
      actions of OFS, we studied high-fat-fed diabetic mice treated with OFS for 4
      weeks in the presence or absence of the GLP-1 receptor antagonist exendin 9-39
      (Ex-9). OFS improved glucose tolerance, fasting blood glucose, glucose-stimulated
      insulin secretion, and insulin-sensitive hepatic glucose production and reduced
      body weight gain. Ex-9 totally prevented the beneficial effects of OFS.
      Furthermore, GLP-1 receptor knockout mice (GLP-1R(-/-)) were completely
      insensitive to the antidiabetic actions of OFS. At the molecular level, the
      effects of OFS on endogenous glucose production correlated with changes of
      hepatic IRS (insulin receptor substrate)-2 and Akt phosphorylation in an Ex-9
      dependent manner. As inflammation is associated with diabetes and obesity, we
      quantified nuclear factor-kappaB and inhibitor of kappaB kinase beta in the
      liver. The activity of both intracellular inflammatory effectors was reduced by
      OFS but, importantly, this effect could not be reverted by Ex-9. In summary, our
      data show that the antidiabetic actions of OFS require a functional GLP-1
      receptor. These findings highlight the therapeutic potential of enhancing
      endogenous GLP-1 secretion for the treatment of type 2 diabetes.

PMID- 16644710
TI  - Plasma phospholipid transfer protein activity is decreased in type 2 diabetes
      during treatment with atorvastatin: a role for apolipoprotein E?
AB  - Plasma phospholipid transfer protein (PLTP) plays an important role in
      lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a
      condition with strongly elevated risk for coronary heart disease. The aim of this
      study was to test the hypothesis that statins reduce PLTP activity and to examine
      the potential role of apolipoprotein E (apoE). PLTP activity and apoE were
      measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin
      Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled
      trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was
      positively correlated with waist circumference, HbA(1c), glucose, and apoE (all P
      < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg
      atorvastatin: -8.3%, P < 0.05; 80 mg atorvastatin: -12.1%, P < 0.002). Plasma
      apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was
      strongly related to the decrease in PLTP activity (r = 0.565, P < 0.001). The
      change in apoE remained the sole determinant of the change in PLTP activity in a
      multivariate model. The activity of PLTP in type 2 diabetes is decreased by
      atorvastatin. The association between the decrease in PLTP activity and apoE
      during statin treatment supports the hypothesis that apoE may prevent PLTP
      inactivation.

PMID- 16644711
TI  - A functional Tyr1306Cys variant in LARG is associated with increased insulin
      action in vivo.
AB  - Diminished insulin sensitivity is a characteristic feature of type 2 diabetes.
      Inhibition of insulin action, resulting in reduced skeletal muscle glucose
      uptake, is mediated in part through stimulation of RhoA activity. One regulator
      of RhoA activity is leukemia-associated Rho guanine nucleotide exchange factor
      (LARG). The LARG gene maps to a region on chromosome 11q23-24 that shows genetic
      linkage to BMI and type 2 diabetes in Pima Indians. Because of its role in RhoA
      activation, the LARG gene was analyzed as a positional candidate gene for this
      linkage. Sequencing of the LARG gene and genotyping of variants identified
      several polymorphisms that were associated with in vivo rates of insulin-mediated
      glucose uptake, at both physiological and maximally stimulating insulin
      concentrations, among 322 nondiabetic Pima Indians who had undergone a
      hyperinsulinemic-euglycemic clamp. The strongest association with rate of glucose
      uptake was found with a Tyr1306Cys polymorphism (P < 0.0001, adjusted for age,
      sex, percent body fat, and nuclear family membership). In transient transfection
      studies in NIH3T3 cells, the LARG(Cys1306) protein had reduced activity compared
      with LARG(Tyr1306) protein (P < 0.05). We propose that the Tyr1306Cys
      substitution in LARG, through its differential activation of RhoA, increases
      insulin sensitivity in nondiabetic Pima Indians.

PMID- 16644712
TI  - Variation in the UCP2-UCP3 gene cluster predicts the development of type 2
      diabetes in healthy middle-aged men.
AB  - The impact of the UCP2 -866G>A and UCP3 -55C>T variants on prospective risk of
      type 2 diabetes was examined over 15 years in 2,936 healthy middle-aged men (mean
      age 56 years). Conversion to diabetes (n = 169) was associated with higher BMI,
      blood pressure, cholesterol, triglycerides and C-reactive protein. The hazard
      ratio (HR) for diabetes of a BMI >30 kg/m(2) was 3.96 (95% CI 2.87-5.47).
      Homozygosity for the UCP2A or UCP3T alleles accelerated the onset of diabetes,
      with significant differences in risk of diabetes at 10 years (HR [95% CI] UCP2AA
      vs. GA+GG 1.94 [1.18-3.19], P = 0.009; UCP3TT vs. CC+ CT 2.06 [1.06-3.99], P =
      0.03) but less so at 15 years (UCP2AA 1.42 [0.92-2.19], P = 0.1; UCP3TT 1.57
      [0.87-2.04], P = 0.13). Men who were homozygous for both UCP2AA and UCP3TT (1.5%
      of men) had a risk for diabetes at 10 years of 4.20 (1.70-10.37), P = 0.002.
      These genotype effects were additive with obesity, and men with a BMI >30 kg/m(2)
      and this genotype combination had a 10-year risk of diabetes of 19.23 [5.63
      63.69], P < 0.0001. Functional promoter variants UCP2 and UCP3 increase the
      prospective risk of diabetes. Although the mechanism of the UCP2 effect is likely
      to be caused by increased expression in the pancreas and subsequent reduced
      insulin secretion, the mechanism of the UCP3 effect is currently unknown. Both
      effects are exacerbated by obesity.

PMID- 16644713
TI  - Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in
      patients with type 2 diabetes.
AB  - Adiponectin is an adipocyte-derived hormone that has shown anti-inflammatory and
      antiatherogenic effects. We assessed the associations of variants in the
      adiponectin gene (ADIPOQ) with circulating adiponectin levels and cardiovascular
      risk among women with type 2 diabetes. Of 989 diabetic women from the Nurses'
      Health Study, 285 developed cardiovascular disease (CVD) during follow-up through
      2000. We genotyped five ADIPOQ polymorphisms in the CVD case and control
      subjects. A promoter polymorphism -11365C-->G was significantly associated with
      lower plasma adiponectin levels (P = 0.004). The homozygotes of allele -4034C
      were significantly associated with approximately 60% increased cardiovascular
      risk (odds ratio 1.62 [95% CI 1.07-2.45]). Adjustment for age, BMI, and other
      covariates did not appreciably change the associations. In addition, a common
      haplotype possessing allele +276T (CAATT) was associated with a significantly
      lower CVD risk than the most common haplotype (CAATG) (0.70 [0.50-0.98]). In our
      meta-analysis of 827 CVD case and 1,887 CVD-free control subjects, polymorphism
      +276G-->T was significantly associated with approximately 45% (20-62%) decreased
      CVD risk under a recessive inheritance mode in diabetic patients. In conclusion,
      ADIPOQ promoter polymorphism -11365C-->G was associated with plasma adiponectin
      levels, whereas polymorphisms -4034A-->C and +276G-->T were associated with CVD
      risk in diabetic patients.

PMID- 16644714
TI  - Differential transmission of type 1 diabetes from diabetic fathers and mothers to
      their offspring.
AB  - We studied the incidence of type 1 diabetes in the offspring of patients with
      childhood- and adolescent-onset type 1 diabetes and several risk factors
      predicting the risk. We defined the diabetes status in the offspring of all
      probands who were included in the nationwide register of Finnish type 1 diabetic
      patients diagnosed at the age of < or =17 years from 1965 to 1979. A total of
      5,291 offspring at risk contributed 72,220 person-years of follow-up between 1970
      and 2003. Of them, 259 offspring developed type 1 diabetes by the end of 2003,
      giving a cumulative incidence of 6.7% (95% CI 5.9-7.5) by the age of 20 years.
      The incidence of type 1 diabetes in the offspring between the years 1980 and 2003
      was 35.3, 44.6, and 44.6 per 10,000 person-years for the age-groups 0-4, 5-9, and
      10-14 years, respectively. Poisson regression analyses showed a marked increase
      in incidence of 5.3% per year from 1983 to 2003. The greatest increase occurred
      in the youngest offspring, aged 0-4 years. Of the offspring of male probands,
      7.8% were affected by the age of 20 years compared with 5.3% of the offspring of
      female probands (relative risk 1.7 [95% CI 1.3-2.2]). The young age at onset of
      diabetes increased the risk of type 1 diabetes in the offspring of diabetic
      fathers but not in the offspring of diabetic mothers. In conclusion, our findings
      revealed that in the offspring of type 1 diabetic patients, the increase in the
      recurrence risk of type 1 diabetes was not more rapid compared with that in the
      background population. In the multivariate analyses, statistically significant
      predictors of type 1 diabetes in the offspring were male sex of the diabetic
      parent, young age at diagnosis in the male parent, and the more recent year of
      birth of the offspring.

PMID- 16644715
TI  - No evidence for association of OAS1 with type 1 diabetes in unaffected siblings
      or type 1 diabetic cases.
AB  - Type 1 diabetes is a common autoimmune disorder that is strongly clustered in
      families. As the sharing of alleles of the HLA class II genes cannot explain all
      of this aggregation, alleles of multiple other loci are involved. Recently, it
      was reported that an A/G splice-site single nucleotide polymorphism (SNP;
      rs10774671) in the OAS1 gene, encoding 2'5'-oligoadenylate synthetase, was
      associated with a protective effect against type 1 diabetes in unaffected
      siblings, and yet affected siblings showed random transmission. Since this
      finding is difficult to explain biologically, we genotyped the OAS1 SNP in 1,552
      type 1 diabetic families from the U.K., U.S., Romania, and Norway and in 4,287
      type 1 diabetic cases and 4,735 control subjects from the U.K. We found no
      evidence of association in either unaffected (relative risk 1.00; P = 0.94) or
      affected (1.00; P = 0.96) siblings or in the case-control study (odds ratio 0.99;
      P = 0.83). These results suggest that additional evidence of association of a low
      penetrance effect in common disease should be sought when the primary result
      comes from unaffected siblings in the absence of any effect in cases.

PMID- 16644716
TI  - Variants of the interleukin-10 promoter gene are associated with obesity and
      insulin resistance but not type 2 diabetes in caucasian italian subjects.
AB  - Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been
      associated with obesity and type 2 diabetes. The three polymorphisms -1082G/A, 
      819C/T, and -592C/A in the IL10 promoter were reported to influence IL10
      transcription. We investigated whether these polymorphisms were associated with
      type 2 diabetes and related traits in a cohort of Italian Caucasians comprising
      551 type 2 diabetic and 1,131 control subjects. The -819C/T and -592C/A
      polymorphisms were in perfect linkage disequilibrium (r(2) = 1.0). The -1082G/A
      polymorphism was not associated with type 2 diabetes or related traits. Although
      the -592C/A polymorphism was not associated with type 2 diabetes, nondiabetic
      homozygous carriers of the A allele showed increased BMI and insulin resistance
      and lower plasma IL-10 levels compared with the other genotypes. In the
      nondiabetic group, the ATA haplotype was associated with an increased risk for
      obesity (odds ratio 1.28 [95% CI 1.02-1.60]; P = 0.02). The ATA/ATA composite
      genotype was associated with an increased risk for obesity (1.96 [1.16-3.31]; P =
      0.01) and insulin resistance (1.99 [1.12-3.53]; P = 0.01). This study suggests
      that polymorphisms and haplotypes of the IL10 promoter may be associated with
      obesity and insulin resistance in a large sample of Italian Caucasians.

PMID- 16644718
TI  - Childhood injuries caused by falling televisions.
AB  - OBJECTIVES: To obtain a detailed description of the injury scene in an attempt to
      identify methods for prevention and to describe the morbidity and mortality of
      children who present to an urban pediatric emergency department (ED) with an
      injury caused by a falling television. METHODS: A retrospective descriptive study
      from a prospectively created database was conducted over one year. All adults
      accompanying a child younger than 13 years of age who was injured by a falling
      television were directly interviewed, and the patient medical charts were
      reviewed. RESULTS: Twenty-eight children were eligible, and 26 children were
      analyzed. The median age was 40 months (25th and 75th quartiles: 31, 51 months).
      None of the televisions, or the furniture that they were placed on, were secured.
      Most parents (85%) reported that they were unaware that injuries could occur by
      this mechanism. Fourteen children suffered head injuries, and nine children
      injured an extremity. Nine children were hospitalized, including two patients
      admitted to the intensive care unit (ICU). CONCLUSIONS: Children may present to
      the ED with injuries caused by falling televisions. These injuries are usually
      not severe; however, the potential for severe injury exists, and some children
      may require ICU monitoring. Our data indicate a lack of parental awareness and an
      absence of primary prevention as a root cause for this problem. Thus, more
      aggressive education to warn parents about the risk of injury must be implemented
      so that more families will take the time to place their televisions safely.

PMID- 16644720
TI  - Functional proteomics identifies protein-tyrosine phosphatase 1B as a target of
      RhoA signaling.
AB  - Rho GTPases are signal transduction effectors that control cell motility, cell
      attachment, and cell shape by the control of actin polymerization and tyrosine
      phosphorylation. To identify cellular targets regulated by Rho GTPases, we
      screened global protein responses to Rac1, Cdc42, and RhoA activation by two
      dimensional gel electrophoresis and mass spectrometry. A total of 22 targets were
      identified of which 19 had never been previously linked to Rho GTPase pathways,
      providing novel insight into pathway function. One novel target of RhoA was
      protein-tyrosine phosphatase 1B (PTP1B), which catalyzes dephosphorylation of key
      signaling molecules in response to activation of diverse pathways. Subsequent
      analysis demonstrated that RhoA enhances post-translational modification of
      PTP1B, inactivates phosphotyrosine phosphatase activity, and up-regulates
      tyrosine phosphorylation of p130Cas, a key mediator of focal adhesion turnover
      and cell migration. Thus, protein profiling reveals a novel role for PTP1B as a
      mediator of RhoA-dependent phosphorylation of p130Cas.

PMID- 16644721
TI  - Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1.
AB  - Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes. Mutations in Btk
      cause X-linked agammaglobulinemia in humans. However, the mechanism of activation
      and signaling of this enzyme has not been fully investigated. We have here shown
      that the peptidylprolyl cis/trans isomerase (PPIase) Pin1 is a negative regulator
      of Btk, controlling its expression level by reducing its half-life, whereas the
      catalytic activity of Btk was unaffected. The negative regulatory effect of Pin1
      was observed both in cell lines and in Pin(-/-) mice and was found to be
      dependent on a functionally intact Btk. This may constitute a feedback loop for
      the regulation of Btk. The target region in Btk was localized to the pleckstrin
      homology domain suggesting that interphase phosphorylation of serine 115 (Ser
      115) in Btk is required, whereas mitosis phosphorylation of serine 21 (Ser-21) is
      critical. Accordingly, Pin 1 was shown to associate with Btk through binding to
      Ser-21 and -115, respectively, both of which lie in a classical Pin1-binding
      pocket. Using a phosphomitotic antibody, it was found that Btk harbors a bona
      fide MPM2 epitope corresponding to a phosphorylated serine or threonine residue
      followed by a proline. Our results indicate that the peptidylprolyl isomerase
      Pin1 interacts with Btk in a cell cycle-dependent manner, regulating the Btk
      expression level.

PMID- 16644722
TI  - Identification and characterization of a new class of bilin lyase: the cpcT gene
      encodes a bilin lyase responsible for attachment of phycocyanobilin to Cys-153 on
      the beta-subunit of phycocyanin in Synechococcus sp. PCC 7002.
AB  - Synechococcus sp. PCC 7002 and all other cyanobacteria that synthesize
      phycocyanin have a gene, cpcT, that is paralogous to cpeT, a gene of unknown
      function affecting phycoerythrin synthesis in Fremyella diplosiphon. A cpcT null
      mutant contains 40% less phycocyanin than wild type and produces smaller
      phycobilisomes with red-shifted absorbance and fluorescence emission maxima.
      Phycocyanin from the cpcT mutant has an absorbance maximum at 634 nm compared
      with 626 nm for the wild type. The phycocyanin beta-subunit from the cpcT mutant
      has slightly smaller apparent molecular weight on SDS-PAGE. Purified phycocyanins
      from the cpcT mutant and wild type were cleaved with formic acid, and the
      products were analyzed by SDS-PAGE. No phycocyanobilin chromophore was bound to
      the peptide containing Cys-153 derived from the phycocyanin beta-subunit of the
      cpcT mutant. Recombinant CpcT was used to perform in vitro bilin addition assays
      with apophycocyanin (CpcA/CpcB) and phycocyanobilin. Depending on the source of
      phycocyanobilin, reaction products with CpcT had absorbance maxima between 597
      and 603 nm as compared with 638 nm for the control reactions, in which
      mesobiliverdin becomes covalently bound. After trypsin digestion and reverse
      phase high performance liquid chromatography, the CpcT reaction product produced
      one major phycocyanobilin-containing peptide. This peptide had a retention time
      identical to that of the tryptic peptide that includes phycocyanobilin-bound,
      cysteine 153 of wild-type phycocyanin. The results from characterization of the
      cpcT mutant as well as the in vitro biochemical assays demonstrate that CpcT is a
      new phycocyanobilin lyase that specifically attaches phycocyanobilin to Cys-153
      of the phycocyanin beta-subunit.

PMID- 16644723
TI  - The glucocorticoid receptor represses cyclin D1 by targeting the Tcf-beta-catenin
      complex.
AB  - The ability of glucocorticoids (GCs) to regulate cell proliferation plays an
      important role in their therapeutic use. The canonical Wnt pathway, which
      promotes the proliferation of many cancers and differentiated tissues, is an
      emerging target for the actions of GCs, albeit existing links between these
      signaling pathways are indirect. By screening known Wnt target genes for their
      ability to respond differently to GCs in cells whose proliferation is either
      positively or negatively regulated by GCs, we identified c-myc, c-jun, and cyclin
      D1, which encode rate-limiting factors for G(1) progression of the cell cycle.
      Here we show that in U2OS/GR cells, which are growth-arrested by GCs, the
      glucocorticoid receptor (GR) represses cyclin D1 via Tcf-beta-catenin, the
      transcriptional effector of the canonical Wnt pathway. We demonstrate that GR can
      bind beta-catenin in vitro, suggesting that GC and Wnt signaling pathways are
      linked directly through their effectors. Down-regulation of beta-catenin by RNA
      interference impeded the expression of cyclin D1 but not of c-myc or c-jun and
      had no significant effect on the proliferation of U2OS/GR cells. Although these
      results revealed that beta-catenin and cyclin D1 are not essential for the
      regulation of U2OS/GR cell proliferation, considering the importance of the Wnt
      pathway for proliferation and differentiation of other cells, the repression of
      Tcf-beta-catenin activity by GR could open new possibilities for tissue-selective
      GC therapies.

PMID- 16644724
TI  - Cytoplasmic IRE1alpha-mediated XBP1 mRNA splicing in the absence of nuclear
      processing and endoplasmic reticulum stress.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates an
      intracellular signal transduction program termed the unfolded protein response
      (UPR). In mammalian cells, the UPR is signaled in part through dimerization of ER
      membrane-localized IRE1alpha to activate its protein kinase and endoribonuclease
      activities. Activated IRE1alpha cleaves XBP1 mRNA at two sites to initiate an
      unconventional splicing reaction. The 5' and 3' fragments are subsequently joined
      by an RNA ligase activity, thereby removing a 26-base intron. This splicing
      reaction creates a translational frameshift to produce a functional XBP1
      transcription factor. However, the cellular location and physiological processes
      required for splicing of XBP1 mRNA are not well characterized. To study these
      processes, XBP1 mRNAs were engineered in which translation of enhanced green
      fluorescence protein or luciferase required splicing of the XBP1 intron. Using
      cell lines that continuously or transiently express these reporter constructs, we
      show that cytoplasmic unspliced XBP1 mRNA is efficiently spliced by activated
      IRE1alpha and requires ongoing cellular transcription but not active translation.
      The XBP1 intron was effectively removed from RNA substrates transcribed from T7
      RNA polymerase or delivered directly to the cytoplasm by RNA transfection, thus
      indicating that the splicing reaction does not require nuclear processing of the
      RNA substrate. Analysis of nuclear and cytoplasmic RNA fractions demonstrated
      that XBP1 mRNA splicing occurs in the cytoplasm. Moreover, an artificial F(v)
      IRE1alphaDeltaN was engineered that was able to splice XBP1 mRNA upon chemical
      induced dimerization. These findings demonstrate that IRE1alpha dimerization is
      sufficient to activate XBP1 mRNA splicing in the absence of the UPR. We propose
      that XBP1 mRNA cytoplasmic splicing provides a novel mechanism to rapidly induce
      translation of a transcription factor in response to a specific stimulus.

PMID- 16644725
TI  - Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing
      factor (AIF) isoform with NADH oxidase activity.
AB  - Apoptosis-inducing factor (AIF) is a bifunctional NADH oxidase involved in
      mitochondrial respiration and caspase-independent apoptosis. Three alternatively
      spliced mRNA isoforms of AIF have been identified previously: AIF, AIF-exB, and
      AIFsh. Here, we report the cloning and the biochemical characterization of a new
      isoform named AIF short 2 (AIFsh2). AIFsh2 transcript includes a previously
      unknown exon placed between exons 9 and 10 of AIF. The resulting AIFsh2 protein,
      which localizes in mitochondria, corresponds to the oxidoreductase domain of AIF.
      In this way, AIFsh2 exhibits similar NADH oxidase activity to AIF and generates
      reactive oxygen species. Like AIF, AIFsh2 is released from mitochondria to
      cytosol after an apoptotic insult in a calpain or cathepsin-dependent manner.
      However, in contrast to AIF, AIFsh2 does not induce nuclear apoptosis. Thus, it
      seems that the reactive oxygen species produced by the oxidoreductase domain of
      AIF/AIFsh2 are not important for AIF-dependent nuclear apoptosis. In addition, we
      demonstrate that the AIFsh2 mRNA is absent in normal brain tissue, whereas it is
      expressed in neuroblastoma-derived cells, suggesting a different regulation in
      normal and transformed cells from the brain lineage. Together, our results reveal
      that AIF yields an original and independent genetic regulation of the two AIF
      functions. This is an important issue to understand the physiological role of
      this protein.

PMID- 16644726
TI  - Regulation of rat hepatic L-pyruvate kinase promoter composition and activity by
      glucose, n-3 polyunsaturated fatty acids, and peroxisome proliferator-activated
      receptor-alpha agonist.
AB  - Carbohydrate regulatory element-binding protein (ChREBP), MAX-like factor X
      (MLX), and hepatic nuclear factor-4alpha (HNF-4alpha) are key transcription
      factors involved in the glucose-mediated induction of hepatic L-type pyruvate
      kinase (L-PK) gene transcription. n-3 polyunsaturated fatty acids (PUFA) and
      WY14643 (peroxisome proliferator-activated receptor alpha (PPARalpha) agonist)
      interfere with glucose-stimulated L-PK gene transcription in vivo and in rat
      primary hepatocytes. Feeding rats a diet containing n-3 PUFA or WY14643
      suppressed hepatic mRNA(L-PK) but did not suppress hepatic ChREBP or HNF-4alpha
      nuclear abundance. Hepatic MLX nuclear abundance, however, was suppressed by n-3
      PUFA but not WY14643. In rat primary hepatocytes, glucose-stimulated accumulation
      of mRNA(LPK) and L-PK promoter activity correlated with increased ChREBP nuclear
      abundance. This treatment also increased L-PK promoter occupancy by RNA
      polymerase II (RNA pol II), acetylated histone H3 (Ac-H3), and acetylated histone
      H4 (Ac-H4) but did not significantly impact L-PK promoter occupancy by ChREBP or
      HNF-4alpha. Inhibition of L-PK promoter activity by n-3 PUFA correlated with
      suppressed RNA pol II, Ac-H3, and Ac-H4 occupancy on the L-PK promoter. Although
      n-3 PUFA transiently suppressed ChREBP and MLX nuclear abundance, this treatment
      did not impact ChREBP-LPK promoter interaction. HNF4alpha-LPK promoter
      interaction was transiently suppressed by n-3 PUFA. Inhibition of L-PK promoter
      activity by WY14643 correlated with a transient decline in ChREBP nuclear
      abundance and decreased Ac-H4 interaction with the L-PK promoter. WY14643,
      however, had no impact on MLX nuclear abundance or HNF4alpha-LPK promoter
      interaction. Although overexpressed ChREBP or HNF-4alpha did not relieve n-3 PUFA
      suppression of L-PK gene expression, overexpressed MLX fully abrogated n-3 PUFA
      suppression of L-PK promoter activity and mRNA(L-PK) abundance. Overexpressed
      ChREBP, but not MLX, relieved the WY14643 inhibition of L-PK. In conclusion, n-3
      PUFA and WY14643/PPARalpha target different transcription factors to control L-PK
      gene transcription. MLX, the heterodimer partner for ChREBP, has emerged as a
      novel target for n-3 PUFA regulation.

PMID- 16644727
TI  - Composition of perineuronal net extracellular matrix in rat brain: a different
      disaccharide composition for the net-associated proteoglycans.
AB  - We developed a method to extract differentially chondroitin sulfate proteoglycans
      (CSPGs) that are diffusely present in the central nervous system (CNS) matrix and
      CSPGs that are present in the condensed matrix of perineuronal nets (PNNs). Adult
      rat brain was sequentially extracted with Tris-buffered saline (TBS), TBS
      containing detergent, 1 m NaCl, and 6 m urea. Extracting tissue sections with
      these buffers showed that the diffuse and membrane-bound CSPGs were extracted in
      the first three buffers, but PNN-associated CSPGs remained and were only removed
      by 6 m urea. Most of the CSPGs were extracted to some degree with all the
      buffers, with neurocan, brevican, aggrecan, and versican particularly associated
      with the stable urea-extractable PNNs. The CSPGs in stable complexes only
      extractable in urea buffer are found from postnatal day 7-14 coinciding with PNN
      formation. Disaccharide composition analysis indicated a different
      glycosaminoglycan (GAG) composition for PGs strongly associated with
      extracellular matrix (ECM). For CS/dermatan sulfate (DS)-GAG the content of
      nonsulfated, 6-O-sulfated, 2,6-O-disulfated, and 4,6-O-disulfated disaccharides
      were higher and for heparan sulfate (HS)-GAG, the content of 6-O-sulfated, 2-N-,
      6-O-disulfated, 2-O-, 2-N-disulfated, and 2-O-, 2-N-, 6-O-trisulfated
      disaccharides were higher in urea extract compared with other buffer extracts.
      Digestions with chondroitinase ABC and hyaluronidase indicated that aggrecan,
      versican, neurocan, brevican, and phosphacan are retained in PNNs through binding
      to hyaluronan (HA). A comparison of the brain and spinal cord ECM with respect to
      CSPGs indicated that the PNNs in both parts of the CNS have the same composition.

PMID- 16644728
TI  - Protective effects of catalase overexpression on UVB-induced apoptosis in normal
      human keratinocytes.
AB  - UV-induced apoptosis in keratinocytes is a highly complex process in which
      various molecular pathways are involved. These include the extrinsic pathway via
      triggering of death receptors and the intrinsic pathway via DNA damage and
      reactive oxygen species (ROS) formation. In this study we investigated the effect
      of catalase and CuZn-superoxide dismutase (SOD) overexpression on apoptosis
      induced by UVB exposure at room temperature or 4 degrees C on normal human
      keratinocytes. Irradiation at low temperature reduced UV-induced apoptosis by 40%
      in normal keratinocytes independently of any change in p53 and with a decrease in
      caspase-8 activation. Catalase overexpression decreased apoptosis by 40% with a
      reduction of caspase-9 activation accompanied by a decrease in p53. Keeping cells
      at low temperature and catalase overexpression had additive effects. CuZn-SOD
      overexpression had no significant effect on UVB-induced apoptosis. UVB induced an
      increase in ROS levels at two distinct stages: immediately following irradiation
      and around 3 h after irradiation. Catalase overexpression inhibited only the late
      increase in ROS levels. We conclude that catalase overexpression has a protective
      role against UVB irradiation by preventing DNA damage mediated by the late ROS
      increase.

PMID- 16644729
TI  - DdPDE4, a novel cAMP-specific phosphodiesterase at the surface of dictyostelium
      cells.
AB  - Dictyostelium discoideum cells possess multiple cyclic nucleotide
      phosphodiesterases that belong either to class I enzymes that are present in all
      eukaryotes or to the rare beta-lactamase class II. We describe here the
      identification and characterization of DdPDE4, the third class I enzyme of
      Dictyostelium. The deduced amino acid sequence predicts that DdPDE4 has a leader
      sequence, two transmembrane segments, and an extracellular catalytic domain that
      exhibits a high degree of homology with human cAMP-specific PDE8. Expression of
      the catalytic domain of DdPDE4 shows that the enzyme is a cAMP-specific
      phosphodiesterase with a K(m) of 10 microm; cGMP is hydrolyzed at least 100-fold
      more slowly. The full-length protein is shown to be membrane-bound with catalytic
      activity exposed to the extracellular medium. Northern blots and activity
      measurements reveal that expression of DdPDE4 is low during single cell stages
      and increases at 9 h of starvation, corresponding with mound stage. A function
      during multicellular development is confirmed by the phenotype of ddpde4(-) knock
      out strains, showing normal aggregation but impaired development from the mound
      stage on. These results demonstrate that DdPDE4 is a unique membrane-bound
      phosphodiesterase with an extracellular catalytic domain regulating intercellular
      cAMP during multicellular development.

PMID- 16644730
TI  - Role of MyD88 in phosphatidylinositol 3-kinase activation by flagellin/toll-like
      receptor 5 engagement in colonic epithelial cells.
AB  - Bacterial flagellin, recognized by Toll-like receptor (TLR) 5, is suggested to be
      involved in colonic inflammation. However, the detailed signaling mechanisms
      mediated by flagellin/TLR5 engagement are not clear. Here we dissected the
      biochemical mechanism by which TLR5 engagement mediates phosphatidylinositol 3
      kinase (PI3K) activation in colonic epithelial cells. We demonstrate that
      silencing TLR5 expression in nontransformed human colonic epithelial cells blocks
      flagellin-induced PI3K activation, indicating specific activation of PI3K by
      flagellin/TLR5 engagement. Moreover, we determine that TLR5 recruits the p85
      regulatory subunit of PI3K to its cytoplasmic TIR domain in response to
      flagellin. However, the Src homology binding "YXXM" motif in the cytoplasmic TIR
      domain of TLR5 is not involved in p85 recruitment, implying that TLR5 indirectly
      recruits p85. Indeed, we demonstrate that the adaptor molecule MyD88 associates
      with TLR5 and silencing MyD88 expression blocks PI3K activation by disrupting the
      association between TLR5 and p85. Furthermore, we show that MyD88 associates with
      p85 in response to flagellin. Additionally, we determine that blocking PI3K
      activation reduces interleukin-8 production induced by flagellin in human colonic
      epithelial cells. Together, MyD88 bridges TLR5 engagement to PI3K activation in
      response to flagellin.

PMID- 16644731
TI  - Nuclear localization in the biology of the CD40 receptor in normal and neoplastic
      human B lymphocytes.
AB  - CD40 is a tumor necrosis factor (TNF) receptor superfamily, (TNFR; TNFRSF-5)
      member, that initiates important signaling pathways mediating cell growth,
      survival, and differentiation in B-lymphocytes. Although CD40 has been
      extensively studied as a plasma membrane-associated growth factor receptor, we
      demonstrate here that CD40 is present not only in the plasma membrane and
      cytoplasm but also in the nucleus of normal and neoplastic B-lymphoid cells.
      Confocal microscopy showed that transfected CD40-green fluorescent fusion protein
      entered B-cell nuclei. The CD40 protein contains a nuclear localization signal
      sequence that, when mutated, blocks entry of CD40 into the nucleus through the
      classic karyopherins (importins-alpha/beta) pathway. Nuclear fractionation
      studies revealed the presence of CD40 protein in the nucleoplasm fraction of
      activated B cells, and chromatin immunoprecipitation assays demonstrated that
      CD40 binds to and stimulates the BLyS/BAFF promoter, another TNF family member
      (TNFSF-13B) involved in cell survival in the B cell lineage. Like other nuclear
      growth factor receptors, CD40 appears to be a transcriptional regulator and is
      likely to play a larger and more complex role than previously demonstrated in
      regulating essential growth and survival pathways in B-lymphocytes.

PMID- 16644732
TI  - Identification of a co-repressor that inhibits the transcriptional and growth
      arrest activities of CCAAT/enhancer-binding protein alpha.
AB  - We used a yeast two-hybrid screening approach to identify novel interactors of
      CCAAT/enhancer-binding protein alpha (C/EBPalpha) that may offer insight into its
      mechanism of action and regulation. One clone obtained was that for CA150, a
      nuclear protein previously characterized as a transcriptional elongation factor.
      In this report, we show that CA150 is a widely expressed co-repressor of C/EBP
      proteins. Two-hybrid and co-immunoprecipitation analyses indicated that CA150
      interacts with C/EBPalpha. Overexpression of CA150 inhibited the transactivation
      produced by C/EBPalpha and was also able to reverse the enhancing effect of the
      co-activator p300 on C/EBPbeta-mediated transactivation. Analysis of C/EBPalpha
      mutants indicated that CA150 interacts with C/EBPalpha primarily through a domain
      spanning amino acids 135-150. Chromatin immunoprecipitation assays showed that
      CA150 was present on a promoter that is repressed by C/EBPalpha but not present
      on a promoter that is activated by C/EBPalpha. Finally, we showed that in cells
      in which growth arrest had been induced by ectopic expression of C/EBPalpha,
      CA150 was able to release them from growth arrest. Interestingly, CA150 could not
      reverse the growth arrest produced by the minimal growth-arrest domain of
      C/EBPalpha (amino acids 175-217), suggesting that the effect of CA150 was
      directed at a region of C/EBPalpha outside of this minimal domain, consistent
      with our two-hybrid analysis. Taken together, these data indicate that CA150 is a
      co-repressor of C/EBP proteins and provides a possible mechanism for how
      C/EBPalpha can repress transcription of specific genes.

PMID- 16644733
TI  - Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain
      interactions.
AB  - RhoGEFs are central controllers of small G-proteins in cells and are regulated by
      several mechanisms. There are at least 22 human RhoGEFs that contain SH3 domains,
      raising the possibility that, like several other enzymes, SH3 domains control the
      enzymatic activity of guanine nucleotide exchange factor (GEF) domains through
      intra- and/or intermolecular interactions. The structure of the N-terminal SH3
      domain of Kalirin was solved using NMR spectroscopy, and it folds much like other
      SH3 domains. However, NMR chemical shift mapping experiments showed that this
      Kalirin SH3 domain is unique, containing novel cooperative binding site(s) for
      intramolecular PXXP ligands. Intramolecular Kalirin SH3 domain/ligand
      interactions, as well as binding of the Kalirin SH3 domain to the adaptor protein
      Crk, inhibit the GEF activity of Kalirin. This study establishes a novel
      molecular mechanism whereby intramolecular and intermolecular Kalirin SH3
      domain/ligand interactions modulate GEF activity, a regulatory mechanism that is
      likely used by other RhoGEF family members.

PMID- 16644734
TI  - Differential regulation of the human tyrosine hydroxylase isoforms via
      hierarchical phosphorylation.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of the
      catecholamines dopamine, noradrenaline, and adrenaline. In response to short term
      stimuli TH activity is primarily controlled by phosphorylation of serine 40. We
      have previously shown that phosphorylation of serine 19 in TH can indirectly
      activate TH via a hierarchical mechanism by increasing the rate of
      phosphorylation of serine 40. Here we show that phosphorylation of serine 31 in
      rat TH increases the rate of serine 40 phosphorylation 9-fold in vitro.
      Phosphorylation of serine 31 in intact bovine chromaffin cells potentiated the
      forskolin-induced increase in serine 40 phosphorylation and TH activity more than
      2-fold. Humans are unique in that they contain four TH isoforms but to date no
      significant differences have been shown in the regulation of these isoforms.
      Phosphorylation of the human TH isoform 1 at serine 31 by extracellular signal
      regulated protein kinase (ERK) also produced a 9-fold increase in the rate of
      phosphorylation of serine 40, whereas little effect was seen in the TH isoforms 3
      and 4. ERK did not phosphorylate human TH isoform 2. The effect of serine 19
      phosphorylation on serine 40 (44 in TH2) phosphorylation is stronger in TH2 than
      in TH1. Thus hierarchical phosphorylation provides a mechanism whereby the two
      major human TH isoforms (1 and 2) can be differentially regulated with only
      isoform 1 responding to the ERK pathway, whereas isoform 2 is more sensitive to
      calcium-mediated events.

PMID- 16644735
TI  - The adaptor molecule Lnk negatively regulates tumor necrosis factor-alpha
      dependent VCAM-1 expression in endothelial cells through inhibition of the ERK1
      and -2 pathways.
AB  - Lnk, with APS and SH2-B (Src homology 2-B), belongs to a family of SH2-containing
      proteins with potential adaptor functions. Lnk regulates growth factor and
      cytokine receptor-mediated pathways implicated in lymphoid, myeloid, and platelet
      homeostasis. We have previously shown that Lnk is expressed and up-regulated in
      vascular endothelial cells (ECs) in response to tumor necrosis factor-alpha
      (TNFalpha). In this study, we have shown that, in ECs, Lnk down-regulates the
      expression, at both mRNA and protein levels, of the proinflammatory molecules
      VCAM-1 and E-selectin induced by TNFalpha. Mechanistically, our data indicated
      that, in response to TNFalpha, NFkappaB/p65 phosphorylation and translocation as
      well as IkappaBalpha phosphorylation and degradation were unchanged, suggesting
      that Lnk does not modulate NFkappaB activity. However, Lnk activates
      phosphatidylinositol 3-kinase (PI3K) as reflected by Akt phosphorylation. Our
      results identify endothelial nitric-oxide synthase as a downstream target of Lnk
      mediated activation of the PI3K/Akt pathway and HO-1 as a new substrate of Akt.
      We found that sustained Lnk-mediated activation of PI3K in TNFalpha-activated ECs
      correlated with the inhibition of ERK1/2 phosphorylation, whereas phosphorylation
      of p38 and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinases
      (MAPKs) was unchanged. ERK1/2 inhibition decreases VCAM-1 expression in TNFalpha
      treated ECs. Collectively, our results identify the adaptor Lnk as a negative
      regulator in the TNFalpha-signaling pathway mediating ERK inhibition and suggest
      a role for Lnk in the interplay between PI3K and ERK triggered by TNFalpha in
      ECs.

PMID- 16644736
TI  - Repletion of atypical protein kinase C following RNA interference-mediated
      depletion restores insulin-stimulated glucose transport.
AB  - The role of atypical protein kinase C (aPKC) in insulin-stimulated glucose
      transport in myocytes and adipocytes is controversial. Whereas studies involving
      the use of adenovirally mediated expression of kinase-inactive aPKC in L6
      myocytes and 3T3/L1 and human adipocytes, and data from knock-out of aPKC in
      adipocytes derived from mouse embryonic stem cells and subsequently derived
      adipocytes, suggest that aPKCs are required for insulin-stimulated glucose
      transport, recent findings in studies of aPKC knockdown by small interfering RNA
      (RNAi) in 3T3/L1 adipocytes are conflicting. Moreover, there are no reports of
      aPKC knockdown in myocytes, wherein insulin effects on glucose transport are
      particularly relevant for understanding whole body glucose disposal. Presently,
      we exploited the fact that L6 myotubes and 3T3/L1 adipocytes have substantially
      different (30% nonhomology) major aPKCs, viz. PKC-zeta in L6 myotubes and PKC
      lambda in 3T3/L1 adipocytes, that nevertheless can function interchangeably for
      glucose transport. Accordingly, in L6 myotubes, RNAi-targeting PKC-zeta, but not
      PKC-lambda, markedly depleted aPKC and concomitantly inhibited insulin-stimulated
      glucose transport; more importantly, these depleting/inhibitory effects were
      rescued by adenovirally mediated expression of PKC-lambda. Conversely, in 3T3/L1
      adipocytes, RNAi constructs targeting PKC-lambda, but not PKC-zeta, markedly
      depleted aPKC and concomitantly inhibited insulin-stimulated glucose transport;
      here again, these depleting/inhibitory effects were rescued by adenovirally
      mediated expression of PKC-zeta. These findings in knockdown and, more
      convincingly, rescue studies, strongly support the hypothesis that aPKCs are
      required for insulin-stimulated glucose transport in myocytes and adipocytes.

PMID- 16644737
TI  - Cholesterol accumulation sequesters Rab9 and disrupts late endosome function in
      NPC1-deficient cells.
AB  - Niemann-Pick type C disease is an autosomal recessive disorder that leads to
      massive accumulation of cholesterol and glycosphingolipids in late endosomes and
      lysosomes. To understand how cholesterol accumulation influences late endosome
      function, we investigated the effect of elevated cholesterol on Rab9-dependent
      export of mannose 6-phosphate receptors from this compartment. Endogenous Rab9
      levels were elevated 1.8-fold in Niemann-Pick type C cells relative to wild type
      cells, and its half-life increased 1.6-fold, suggesting that Rab9 accumulation is
      caused by impaired protein turnover. Reduced Rab9 degradation was accompanied by
      stabilization on endosome membranes, as shown by a reduction in the capacity of
      Rab9 for guanine nucleotide dissociation inhibitor-mediated extraction from
      Niemann-Pick type C membranes. Cholesterol appeared to stabilize Rab9 directly,
      as liposomes loaded with prenylated Rab9 showed decreased extractability with
      increasing cholesterol content. Rab9 is likely sequestered in an inactive form on
      Niemann-Pick type C membranes, as cation-dependent mannose 6-phosphate receptors
      were missorted to the lysosome for degradation, a process that was reversed by
      overexpression of GFP-tagged Rab9. In addition to using primary fibroblasts
      isolated from Niemann-Pick type C patients, RNA interference was utilized to
      recapitulate the disease phenotype in cultured cells, greatly facilitating the
      analysis of cholesterol accumulation and late endosome function. We conclude that
      cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick
      type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor
      trafficking.

PMID- 16644738
TI  - Local unfolding in a destabilized, pathogenic variant of superoxide dismutase 1
      observed with H/D exchange and mass spectrometry.
AB  - Hydrogen exchange monitored by mass spectrometry has been used to study the
      structural behavior of the pathogenic A4V variant of superoxide dismutase 1
      (SOD1) in the metal-free (apo) form. Mass spectrometric data revealed that in the
      disulfide-intact (S-S) form, the A4V variant is destabilized at residues 50-53,
      in the disulfide subloop of the dimer interface, but many other regions of the
      A4V protein exhibited hydrogen exchange properties identical to that of the wild
      type protein. Additionally, mass spectrometry revealed that A4V apoSOD1(S-S)
      undergoes slow localized unfolding in a large segment of the beta-barrel that
      included beta3, beta4, and loops II and III. In the disulfide-reduced form, A4V
      apoSOD1 exchanged like a "random coil" polypeptide at 20 degrees C and began to
      populate folded states at 4 degrees C. These local and global unfolding events
      could facilitate intermolecular protein-protein interactions that cause the
      aggregation or neurotoxicity of A4V SOD1.

PMID- 16644739
TI  - Distinct properties of the five UDP-D-glucose/UDP-D-galactose 4-epimerase
      isoforms of Arabidopsis thaliana.
AB  - Plant genomes contain genetically encoded isoforms of most nucleotide sugar
      interconversion enzymes. Here we show that Arabidopsis thaliana has five genes
      encoding functional UDP-D-glucose/UDP-D-galactose 4-epimerase (named UGE1 to
      UGE5). All A. thaliana UDP-d-glucose 4-epimerase isoforms are dimeric in
      solution, maximally active in vitro at 30-40 degrees C, and show good activity
      between pH 7 and pH 9. In vitro, UGE1, -3, and -5 act independently of externally
      added NAD+, whereas cofactor addition stimulates the activity of UGE2 and is
      particularly important for UGE4 activity. UGE1 and UGE3 are most efficiently
      inhibited by UDP. The five isoforms display kcatUDP-Gal values between 23 and 128
      s(-1) and KmUDP-Gal values between 0.1 and 0.3 mm. This results in enzymatic
      efficiencies ranging between 97 and 890 mm(-1) s(-1) for UGE4 = UGE1 < UGE3 <
      UGE5 < UGE2. The KmUDP-Glc values, derived from the Haldane relationship, were
      0.76 mm for UGE1, 0.56 mm for UGE4, and between 0.13 and 0.23 mm for UGE2, -3,
      and -5. The expression of UGE isoforms is ubiquitous and displays developmental
      and cell type-dependent variations. UGE1 and -3 expression patterns globally
      resemble enzymes involved in carbohydrate catabolism, and UGE2, -4, and -5
      expression is more related to carbohydrate biosynthesis. UGE1, -2, and -4 are
      present in the cytoplasm, whereasUGE4 is additionally enriched close to Golgi
      stacks. All UGE genes tested complement the UGE4rhd1 phenotype, confer increased
      galactose tolerance in planta, and complement the galactose metabolization
      deficiency in the Saccharomyces cerevisiae gal10 mutant. We suggest that plant
      UGE isoforms function in different metabolic situations and that enzymatic
      properties, gene expression pattern, and subcellular localization contribute to
      the differentiation of isoform function.

PMID- 16644740
TI  - Chaperoning drug development with PET.

PMID- 16644741
TI  - Nuclear localizing sequences: an innovative way to improve targeted radiotherapy.

PMID- 16644742
TI  - Metabolic imaging of anterior capsular stimulation in refractory obsessive
      compulsive disorder: a key role for the subgenual anterior cingulate and ventral
      striatum.
AB  - High-frequency anterior capsular stimulation is a new, promising, and reversible
      neuromodulatory treatment in the research stage for patients with refractory
      obsessive-compulsive disorder (OCD). The mechanism of action is unknown but
      hypothesized to be secondary to interruption of the corticothalamostriatocortical
      circuit. METHODS: (18)F-FDG PET was performed on 6 consecutive OCD patients
      preoperatively and after stimulation. The results were compared with those of 20
      age- and sex-matched healthy volunteers by using both a standardized volume-of
      interest-based approach for subcortical areas and statistical parametric mapping.
      Correlations were investigated with Yale-Brown Obsessive Compulsive Scale scores
      (Y-BOCS) and Hamilton Depression Rating Scale scores (HAM-D). RESULTS: Chronic
      anterior capsular electrostimulation resulted in a further decrease of prefrontal
      metabolic activity, especially in the subgenual anterior cingulate (P < 0.001).
      Correlation analysis demonstrated that decreases in Y-BOCS and HAM-D with
      anterior capsular electrostimulation were inversely related to the metabolic
      activity changes in the left ventral striatum, left amygdala, and left
      hippocampus (P < 0.01). Preoperative resting metabolic activity in the subgenual
      anterior cingulate was predictive of therapeutic response (P = 0.001).
      CONCLUSION: These observations provide evidence that the subgenual anterior
      cingulate and ventral striatum have a key role in the neuronal circuitry involved
      in the pathophysiology of OCD with associated major depression and in the
      neuromodulatory mechanism of anterior capsular stimulation.

PMID- 16644743
TI  - Safety, biodistribution, and dosimetry of 123I-IMPY: a novel amyloid plaque
      imaging agent for the diagnosis of Alzheimer's disease.
AB  - (123)I-IMPY (6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2-a]pyridine) is a
      novel radiopharmaceutical that selectively binds to Alzheimer's disease (AD)
      amyloid plaques. As a first step toward validating this radiopharmaceutical as an
      imaging biomarker for AD, we measured the whole-body biokinetics and radiation
      dosimetry of (123)I-IMPY in AD patients and cognitively normal control subjects.
      The pharmacologic safety profile of the compound was simultaneously assessed.
      METHODS: The sample included 9 subjects ranging in age from 44 to 80 y. Whole
      body images were obtained for each subject (mean +/- SD, 9.0 +/- 3.2 scans per
      subject) for up to 48 h after the intravenous administration of 185 MBq (5 mCi)
      of (123)I-IMPY. The fraction of administered activity in 12 regions of interest
      was quantified from the attenuation-corrected geometric mean counts in conjugate
      views. Multiexponential functions were iteratively fit to each time-activity
      curve using a nonlinear, least-squares regression algorithm. These curves were
      numerically integrated to yield cumulated activity values for source organs.
      Radiation doses were then estimated with the MIRD technique. RESULTS: The
      radiotracer had no pharmacologic effects (produced no changes in heart rate,
      blood pressure, or laboratory results) on any of the subjects. Radiation
      dosimetry estimates indicated that the dose-limiting organ was the gallbladder,
      which received an average of 0.135 mGy/MBq (range, 0.075-0.198 mGy/MBq). The
      effective dose equivalent and effective dose for (123)I-IMPY were 0.042 +/- 0.003
      mSv/MBq and 0.035 +/- 0.001 mSv/MBq, respectively. The mean effective dose for
      (123)I-IMPY was similar to that for (111)In-diethylenetriaminepentaacetic acid
      (0.035 mGy/MBq), less than half that for (111)In-pentetreotide (0.81 mGy/MBq),
      and approximately twice that for (123)I-IMP (0.018 mGy/MBq). No significant
      differences were found between men and women or between AD patients and control
      subjects. CONCLUSION: (123)I-IMPY may be a safe radiotracer with appropriate
      biokinetics for imaging amyloid plaques in AD patients.

PMID- 16644744
TI  - 18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged
      N0 by clinical examination and CT/MRI.
AB  - (18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role
      in patients with clinically and radiographically negative necks (N0) is less
      clear. In particular, the value of combined PET/CT has not been determined in
      this group of patients. METHODS: In a prospective study, 31 patients with oral
      cancer and no evidence of lymph node metastases by clinical examination or CT/MRI
      underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were
      recorded by neck side (left or right) and lymph node level. PET/CT findings were
      compared with histopathology of dissected nodes, which was the standard of
      reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a
      total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of
      765 dissected lymph nodes harbored metastases. Histopathology revealed nodal
      metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal
      levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative
      in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The
      3 false-negative findings occurred in metastases smaller than 3 mm or because of
      inability to distinguish between primary tumor and adjacent metastasis. TP and
      false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2
      +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on
      the basis of neck sides and 67% and 95% on the basis of number of nodal levels,
      respectively. If a decision regarding the need for neck dissection had been based
      solely on PET/CT, 3 false-negative necks would have been undertreated, and 4
      false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT
      can identify lymph node metastases in a segment of patients with oral cancer and
      N0 neck. A negative test can exclude metastatic deposits with high specificity.
      Despite reasonably high overall accuracy, however, the clinical application of
      PET/CT in the N0 neck may be limited by the combination of limited sensitivity
      for small metastatic deposits and a relatively high number of false-positive
      findings. The surgical management of the N0 neck should therefore not be based on
      PET/CT findings alone.

PMID- 16644745
TI  - PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha
      v beta3 expression.
AB  - (18)F-Galacto-RGD is a new tracer for PET imaging of alpha v beta3, a receptor
      involved in a variety of pathologic processes including angiogenesis and
      metastasis. Our aim was to study the dosimetry of (18)F-galacto-RGD in humans.
      METHODS: Eighteen patients with various tumors (musculoskeletal tumors [n = 10],
      melanoma [n = 5], breast cancer [n = 2], or head and neck cancer [n = 1]) were
      examined. After injection of 133-200 MBq of (18)F-galacto-RGD, 3 consecutive
      emission scans from the thorax to the pelvis were acquired at 6.7 +/- 2.9, 35.6
      +/- 7.6, and 70.4 +/- 12.2 min after injection. Blood samples (n = 4) for
      metabolite analysis were taken 10, 30, and 120 min after injection. The OLINDA
      1.0 program was used to estimate the absorbed radiation dose. RESULTS: Reversed
      phase high-performance liquid chromatography of serum revealed that more than 95%
      of tracer was intact up to 120 min after injection. (18)F-Galacto-RGD showed
      rapid clearance from the blood pool and primarily renal excretion. Background
      activity in lung and muscle tissue was low (percentage injected dose per liter at
      71 min after injection, 0.56 +/- 0.15 and 0.69 +/- 0.25, respectively). The
      calculated effective dose was 18.7 +/- 2.4 microSv/MBq, and the highest absorbed
      radiation dose was in the bladder wall (0.22 +/- 0.03 mGy/MBq). CONCLUSION: (18)F
      Galacto-RGD demonstrates high metabolic stability, a favorable biodistribution,
      and a low radiation dose. Consequently, this tracer can safely be used for
      noninvasive imaging of molecular processes involving the alpha v beta3 integrin
      and for the planning and monitoring of therapeutic approaches targeting alpha v
      beta3.

PMID- 16644746
TI  - 18F-FDG PET reduces unnecessary hemithyroidectomies for thyroid nodules with
      inconclusive cytologic results.
AB  - Fine-needle aspiration biopsy (FNAB) is inconclusive in up to 20% of patients
      with solitary thyroid nodules. In these cases, hemithyroidectomy is necessary,
      but only 20% of the nodules prove to be thyroid carcinoma. The aim of this study
      was to explore the potential of (18)F-FDG PET to reduce the number of unnecessary
      hemithyroidectomies in the preoperative assessment of thyroid nodules with
      inconclusive FNAB results. METHODS: Forty-four consecutive patients, scheduled
      for hemithyroidectomy because of inconclusive FNAB findings, participated in this
      prospective study. (18)F-FDG PET of the thyroid region was performed before
      hemithyroidectomy, and standardized uptake values were calculated. The final
      histopathologic diagnosis served as a standard of reference. RESULTS:
      Histopathologic examination of the surgical specimens revealed 7 well
      differentiated thyroid carcinomas in 6 patients, all accumulating (18)F-FDG
      (negative predictive value, 100%). (18)F-FDG accumulated in 13 of 38 benign
      nodules. The pre-PET probability for cancer in this study population was 14%
      (6/44), and the post-PET probability increased to 32% (6/19). The percentage of
      unnecessary hemithyroidectomies in a hypothetical algorithm using (18)F-FDG PET
      was only 30% (13/44), compared with 86% (38/44) without (18)F-FDG PET. (18)F-FDG
      PET reduced the number of futile hemithyroidectomies by 66% (25/38) (95%
      confidence interval, 49%-80%; Fisher's exact test, P = 0.0038). Semiquantitative
      analysis using standardized uptake values did not help to further reduce this
      number. CONCLUSION: In addition to data in the literature demonstrating accurate
      detection of thyroid cancer by (18)F-FDG PET, this study showed that (18)F-FDG
      PET should play an important role in the management of patients with inconclusive
      cytologic diagnosis of a thyroid nodule. (18)F-FDG PET reduced the number of
      futile hemithyroidectomies by 66%. Although PET is a relatively costly procedure,
      this cost outweighs the costs and risks associated with unnecessary thyroid
      surgery.

PMID- 16644747
TI  - 18F-FET PET differentiation of ring-enhancing brain lesions.
AB  - The aim of this study was to explore the differential diagnostic value of PET
      using the amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) in patients
      with newly diagnosed solitary intracerebral lesions showing ring enhancement on
      contrast-enhanced MRI. METHODS: (18)F-FET PET analyses were performed on 14
      consecutive patients with intracerebral ring-enhancing lesions. Eleven of the
      patients were additionally studied with (18)F-FDG PET. In all patients, the main
      differential diagnosis after MRI was a malignant lesion, in particular
      glioblastoma multiforme, versus a benign lesion, in particular brain abscess. A
      malignant tumor was suspected for lesions showing increased (18)F-FET uptake on
      PET images with a mean lesion-to-brain ratio of at least 1.6 ((18)F-FET PET
      positive). A nonneoplastic lesion was suspected in cases of minimal or absent
      (18)F-FET uptake, with a mean lesion-to-brain ratio of less than 1.6 ((18)F-FET
      PET negative). Histologic diagnosis was obtained by serial biopsies in 13 of the
      14 patients. One patient refused the biopsy, but follow-up indicated an abscess
      because his lesion regressed under antibiotic therapy. RESULTS: Histology and
      clinical follow-up showed high-grade malignant gliomas in 5 patients and
      nonneoplastic lesions in 9 patients. The findings of (18)F-FET PET were positive
      in all 5 glioma patients and in 3 of 9 patients with nonneoplastic lesions,
      including 2 patients with brain abscesses and 1 patient with a demyelinating
      lesion. The findings of (18)F-FDG PET were positive (mean lesion-to-gray matter
      ratio > or = 0.7) in 4 of 4 glioma patients and 3 of 7 patients with
      nonneoplastic lesions. CONCLUSION: Although (18)F-FET PET has been shown to be
      valuable for the diagnostic evaluation of brain tumors, our data indicate that,
      like (18)F-FDG PET, (18)F-FET PET has limited specificity in distinguishing
      between neoplastic and nonneoplastic ring-enhancing intracerebral lesions. Thus,
      histologic investigation of biopsy specimens remains mandatory to make this
      important differential diagnosis.

PMID- 16644748
TI  - SPECT quantification of benzodiazepine receptor concentration using a dual-ligand
      approach.
AB  - The distribution of benzodiazepine receptors in the human brain has been widely
      studied with SPECT using (123)I-iomazenil and semiquantitative approaches, but
      these methods do not allow quantification of the total receptor site
      concentration available for binding (B'(max)) and of the apparent equilibrium
      dissociation constant (K(d)/V(R)). One of the major obstacles to full
      quantitative studies is that pharmacologic effects preclude the administration to
      humans of the high doses of iomazenil required to displace the labeled ligand
      from the receptors. In this study, we applied a dual-ligand protocol using the
      unlabeled ligand flumazenil, which lacks pharmacologic effects, to quantify all
      binding parameters of the benzodiazepine receptor-(123)I-iomazenil interactions.
      METHODS: (123)I-Iomazenil SPECT and MRI were acquired in 8 healthy volunteers,
      one of whom had participated in a (11)C-flumazenil PET experiment. The
      experimental protocol consisted of injections of (123)I-iomazenil and/or
      unlabeled flumazenil. We developed a kinetic model to integrate the different
      pharmacokinetics of these 2 ligands. To simplify the model, we assumed linear
      relationships between iomazenil and flumazenil parameters and adjusted them using
      a coupled fitting procedure. The resulting constrained 5-parameter model was then
      used to quantify the biologic parameters. RESULTS: Across regions, we obtained
      B'(max) values ranging from 7 to 69 pmol/mL and K(d)V(R) values for IMZ from 2.3
      to 3.7 pmol/mL. There was a close correlation in the B'(max) values calculated in
      the same volunteer using (123)I-iomazenil SPECT and (11)C-flumazenil PET.
      CONCLUSION: The dual-ligand approach can be used to quantify all model parameters
      with acceptable SEs. This work demonstrates a theoretic framework and initial
      application of SPECT to quantify binding parameters.

PMID- 16644749
TI  - Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG
      PET.
AB  - We compared (68)Ga-DOTA-F(ab')(2)-herceptin (DOTA is 1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [HER2 PET]) and (18)F-FDG
      PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor
      17-allylamino-17-demethoxygeldanamycin (17AAG). METHODS: Mice bearing BT474
      breast tumor xenografts were scanned with (18)F-FDG PET and HER2 PET before and
      after 17AAG treatment and then biweekly for up to 3 wk. RESULTS: Within 24 h
      after treatment, a significant decrease in HER2 was measured by HER2 PET, whereas
      (18)F-FDG PET uptake, a measure of glycolysis, was unchanged. Marked growth
      inhibition occurred in treated tumors but became evident only by 11 d after
      treatment. Thus, Her2 downregulation occurs independently of changes in
      glycolysis after 17AAG therapy, and Her2 reduction more accurately predicts
      subsequent tumor growth inhibition. CONCLUSION: HER2 PET is an earlier predictor
      of tumor response to 17AAG therapy than (18)F-FDG PET.

PMID- 16644750
TI  - Coronary CT angiography.
AB  - Advances in multidetector CT (MDCT) technology with submillimeter slice
      collimation and high temporal resolution permit contrast-enhanced imaging of
      coronary arteries and coronary plaque during a single breath hold. Appropriate
      patient preparation, detailed technical and technological knowledge with regard
      to recognition of typical imaging artifacts (such as beam hardening or motion
      artifacts), and the adequate choice of postprocessing techniques to detect
      stenosis and plaque are prerequisites to achieving diagnostic image quality. A
      growing number of studies have suggested that 64-slice coronary CT angiography is
      highly accurate for the exclusion of significant coronary artery stenosis (>50%
      luminal narrowing), with negative predictive values of 97%-100%, in comparison
      with invasive selective coronary angiography. In addition, several studies have
      indicated that MDCT also can detect calcified and noncalcified coronary
      atherosclerotic plaques, especially in proximal vessel segments, showing a good
      correlation with intracoronary ultrasound. Studies on clinical utility, cost, and
      cost-effectiveness are now warranted to demonstrate whether and how this
      technique can change and improve the current management of patients with
      suspected or confirmed coronary artery disease.

PMID- 16644751
TI  - Electron- and positron-emitting radiolanthanides for therapy: aspects of
      dosimetry and production.
AB  - All lanthanides have similar chemical properties regarding labeling. Therefore,
      radiolanthanides that have been used for therapy, such as (153)Sm and (177)Lu,
      might easily be replaced with other radiolanthanides. The aim of this work was to
      investigate the suitability of electron- and positron-emitting radiolanthanides
      for radionuclide therapy with reference to dosimetry and production
      possibilities. METHODS: Radiolanthanides with half-lives of 1 h to 15 d, stable
      or long-lived daughters, and limited photon emission were selected. The ratio of
      the absorbed dose rate to the tumors and the normal tissue (TND) was calculated
      for different tumor sizes and compared with the TND values for (90)Y and (131)I.
      The normal tissue and tumors were simulated as an ellipsoid and spheres,
      respectively. The TND values depend on the physical parameters of the
      radionuclides, the tumor size, and the ratio between the activity concentrations
      in the tumor and normal tissue (TNC). RESULTS: (153)Sm, (161)Tb, (169)Er,
      (175)Yb, and (177)Lu had the highest TND values for most of the tumor sizes
      studied. Among these radiolanthanides, (161)Tb and (177)Lu are the only ones that
      can be produced no-carrier-added (nca) and with high specific activities. The
      Auger-electron emitters (161)Ho and (167)Tm had high TND values for tumors
      weighing less than 1 mg and can be produced nca and with high specific
      activities. (142)Pr, (145)Pr, and (166)Ho showed TND values similar to those of
      (90)Y. (166)Ho is generator produced and can be obtained nca and at high specific
      activities. (143)Pr, (149)Pm, (150)Eu, (159)Gd, (165)Dy, (176m)Lu, and (179)Lu
      had higher TND values than did (90)Y for all tumor sizes studied, but only
      (149)Pm can be produced nca and at high specific activities. The other electron
      emitting radiolanthanides and the positron-emitting radiolanthanides showed low
      TND values for all tumor sizes because of the high photon contribution.
      CONCLUSION: The low-energy electron emitters (161)Tb, (177)Lu, and (167)Tm might
      be suitable for radionuclide therapy. The Auger-electron emitter (161)Ho might
      not be suitable for systemic radionuclide therapy (intravenous injection) because
      of its short half-life but might be suitable for local therapy (e.g., in body
      cavities). If higher electron energy is needed, (149)Pm or (166)Ho might be
      suitable for radionuclide therapy.

PMID- 16644752
TI  - Estimation of serotonin transporter parameters with 11C-DASB in healthy humans:
      reproducibility and comparison of methods.
AB  - The aim of the present study was to define the optimal analytic method to derive
      accurate and reliable serotonin transporter (SERT) receptor parameters with (11)C
      3-amino-4-(2-[(dimethylamino)methyl]phenylthio)benzonitrile ((11)C-DASB).
      METHODS: Nine healthy subjects (5 females, 4 males) underwent two (11)C-DASB PET
      scans on the same day. Five analytic methods were used to estimate binding
      parameters in 10 brain regions: compartmental modeling with 1- and 2-tissue
      compartment models (1TC and 2TC), data-driven estimation of parametric images
      based on compartmental theory (DEPICT) analysis, graphical analysis, and the
      simplified reference tissue model (SRTM). Two variations in the fitting procedure
      of the SRTM method were evaluated: nonlinear optimization and basis function
      approach. The test/retest variability (VAR) and intraclass correlation
      coefficient (ICC or reliability) were assessed for 3 outcome measures:
      distribution volume (V(T)), binding potential (BP), and specific to nonspecific
      equilibrium partition coefficient (V(3)''). RESULTS: All methods gave similar
      values across all regions. The variability of V(T) was excellent (< or =10%) in
      all regions, for the 1TC, 2TC, DEPICT, and graphical approaches. The variability
      of BP and V(3)'' was good in regions of high SERT density and poorer in regions
      of moderate and lower densities. The ICC of all 3 outcome measures was excellent
      in all regions. The basis function implementation of SRTM demonstrated improved
      reliability compared with nonlinear optimization, particularly in moderate and
      low-binding regions. CONCLUSION: The results of this study indicate that (11)C
      DASB can be used to measure SERT parameters with high reliability and low
      variability in receptor-rich regions of the brain, with somewhat less reliability
      and increased variability in regions of moderate SERT density and poor
      reproducibility in low-density regions.

PMID- 16644753
TI  - Nuclear localizing sequences promote nuclear translocation and enhance the
      radiotoxicity of the anti-CD33 monoclonal antibody HuM195 labeled with 111In in
      human myeloid leukemia cells.
AB  - Our objective was to evaluate the toxicity of the anti-CD33 monoclonal antibody
      HuM195 modified with peptides (CGYGPKKKRKVGG) harboring the nuclear localizing
      sequence (NLS; underlined) of simian virus 40 large T antigen and labeled with
      (111)In against acute myeloid leukemia (AML) cells. METHODS: HuM195 was
      derivatized with sulfosuccinimidyl-4-(N-maleimidomethyl)-cyclohexane-1
      carboxylate (sulfo-SMCC) to introduce maleimide groups for reaction with NLS
      peptides and then conjugated with diethylenetriaminepentaacetic acid for labeling
      with (111)In. The immunoreactivity of NLS-HuM195 was evaluated by its ability to
      displace the binding of (111)In-HuM195 to HL-60 leukemia cells. Nuclear
      localization was measured in HL-60 cells by subcellular fractionation. The
      antiproliferative effects of (111)In-NLS-HuM195 and (111)In-HuM195 on HL-60,
      U937, or K562 cells with high, intermediate, or minimal CD33 expression,
      respectively, were studied. The survival of HL-60 cells or patient AML specimens
      treated with (111)In-NLS-HuM195 or (111)In-HuM195 was studied. Normal tissue
      toxicity was evaluated in BALB/c mice injected intravenously with of 3.7 MBq (22
      microg) of (111)In-NLS-HuM195 or (111)In-HuM195. RESULTS: NLS-HuM195 exhibited
      relatively preserved CD33 binding affinity (dissociation constant [K(d)] = 4.3 +/
      1.7 x 10(-9) mol/L to 6.9 +/- 1.3 x 10(-9) mol/L). Nuclear uptake increased from
      10.5% +/- 0.5% for (111)In-HuM195 to 28.5% +/- 4.1% or 65.9% +/- 1.5% for (111)In
      HuM195 substituted with 4 or 8 NLS-peptides, respectively. The inhibitory
      concentrations of 50% (IC(50)) and 90% (IC(90)) for HL-60 cells treated with
      (111)In-NLS-HuM195 were 37 kBq per 10(3) cells and 77-81 kBq per 10(3) cells,
      respectively. The IC(50) and IC(90) values for (111)In-HuM195 were 92 kBq per
      10(3) cells and 203 kBq per 10(3) cells. Growth inhibition was correlated with
      the level of CD33 expression. The survival of HL-60 cells was reduced from 232 +/
      22 colonies (control) to 7 +/- 1 colonies with 1.48 mBq per cell of (111)In-NLS
      HuM195; no colonies were found at 3.33 mBq per cell. The surviving fraction
      decreased >2-fold in 7 of 9 AML specimens treated with an excess of (111)In-NLS
      HuM195 and >10-fold in 2 of these specimens. There were no decreases in body
      weight or hematologic parameters or increases in alanine aminotransferase or
      creatinine in mice administered 3.7 MBq (22 microg) of (111)In-NLS-HuM195 or
      (111)In-HuM195. There was no morphologic damage to the liver or kidneys.
      CONCLUSION: We conclude that NLS-peptides routed (111)In-HuM195 to the nucleus of
      AML cells, where the emitted Auger electrons were lethal. (111)In-NLS-HuM195 is a
      promising targeted radiotherapeutic agent for AML.

PMID- 16644754
TI  - In vitro evaluation of adenosine 5'-monophosphate as an imaging agent of tumor
      metabolism.
AB  - Adenosine appears to play an important role in tumor growth and metastasis.
      Synthesized (11)C-adenosine 5'-monophosphate (AMP) has recently been reported as
      a potential tumor-imaging radiotracer. METHODS: A variety of human tumor cell
      lines (SKOV-3, SCC-15, U251, U87, Raji, and Daudi) were incubated with 3.7 kBq
      (0.1 microCi) of [2-(3)H]AMP ((3)H-AMP), [5,6-(3)H]FDG ((3)H-FDG), or [2
      (3)H]adenosine ((3)H-adenosine) in low-physiologic-glucose serum-free medium.
      Selected cells were exposed to caffeine, dipyridamole, adenosine 5'-(alpha,beta
      methylene)diphosphate (APCP), or unlabeled adenosine before exposure to the
      radiotracer. R-phycoerythrin-conjugated mouse antihuman monoclonal antibody to
      human CD73 was used for immunophenotyping. High-performance liquid chromatography
      was used to characterize the intracellular metabolites of (3)H-AMP after
      intracellular uptake. RESULTS: Intracellular uptake of (3)H-AMP was significant
      10 to 100 times the uptake of (3)H-FDG, depending on the particular tumor cell
      line. Preexposure of SKOV-3 cells to caffeine, a competitive inhibitor of
      adenosine receptors, did not affect cellular uptake of (3)H-AMP. However,
      preexposure of SKOV-3 cells to dipyridamole, an equilibrative nucleoside
      transporter inhibitor; APCP, a CD73 (ecto-5'-nucleotidase) inhibitor; or cold
      adenosine significantly inhibited cellular uptake of (3)H-AMP. SKOV-3 uptake of
      (3)H-adenosine was inhibited by dipyridamole but not APCP. U251 uptake of (3)H
      AMP was significantly inhibited by dipyridamole and APCP. U87 uptake of (3)H-AMP
      was only partially inhibited by dipyridamole and APCP. However, Raji and Daudi
      cells had significantly lower uptake of (3)H-AMP than of (3)H-FDG but had
      significantly increased uptake of (3)H-adenosine, which was inhibited by
      dipyridamole. Raji and Daudi cells were negative, but the SKOV-3 cells positive,
      for CD73 cell-surface expression. (3)H-Adenosine metabolites were persistently
      retained after influx into the cell, predominantly as (3)H-adenosine triphosphate
      and (3)H-adenosine diphosphate. CONCLUSION: Cancer cell lines evaluated in vitro
      had significantly elevated uptake of radiolabeled AMP, on the order of 10- to 100
      fold, in comparison to radiolabeled FDG. The mechanism of intracellular uptake
      depends predominantly on equilibrative nucleoside transporters after conversion
      of AMP to adenosine by CD73 in SKOV-3, SCC-15, and U251 cells. Intracellular
      retention is due to phosphorylation to adenosine triphosphate and adenosine
      diphosphate. Raji and Daudi cells have low uptake of radiolabeled AMP because of
      a lack of CD73 expression. This in vitro evaluation using (3)H-AMP with tumor
      cell lines supports the potential of (11)C-AMP for use in targeting the
      nucleoside transport pathway in PET imaging of tumors.

PMID- 16644755
TI  - 111In-benzyl-DTPA-ZHER2:342, an affibody-based conjugate for in vivo imaging of
      HER2 expression in malignant tumors.
AB  - Data on expression of the HER2 (erbB-2) receptor in breast carcinoma make it
      possible to select the most efficient treatment. There are strong indications
      that HER2 expression possesses prognostic and predictive values in ovarian,
      prostate, and lung carcinomas as well. Visualization of HER2 expression using
      radionuclide targeting can provide important diagnostic information. The Affibody
      Z(HER2:342) is a short (approximately 7 kDa) phage-display-selected protein that
      binds HER2 with an affinity of 22 pmol/L. The goal of this study was to evaluate
      whether (111)In-labeled HER2:342 can be used for imaging of HER2 overexpression
      in vivo. METHODS: Z(HER2:342) was labeled with (111)In via isothiocyanate-benzyl
      DTPA (DTPA is diethylenetriaminepentaacetic acid) and the conjugate was
      characterized in vitro and in vivo. RESULTS: (111)In-Benzyl-DTPA-Z(HER2:342)
      preserved the capacity to bind living HER2-expressing cells specifically. The
      affinity of In-benzyl-DTPA-Z(HER2:342) to HER2 was 21 pmol/L according to surface
      plasmon resonance measurements. In nude mice bearing HER2-expressing SKOV-3
      xenografts, a tumor uptake of 12% +/- 3% injected activity per gram and a tumor
      to-blood ratio of about 100 were obtained 4 h after injection. Tumor uptake in
      vivo was receptor specific, as it could be blocked with an excess of nonlabeled
      Z(HER2:342). HER2-expressing xenografts were clearly imaged 4 h after injection
      using a gamma-camera. CONCLUSION: (111)In-Benzyl-DTPA-Z(HER2:342) is a promising
      candidate for visualization of HER2 expression in carcinomas, using the single
      photon detection technique.

PMID- 16644756
TI  - Radioiodine therapy of hepatoma using targeted transfer of the human
      sodium/iodide symporter gene.
AB  - We investigated the feasibility of radioiodine therapy targeting hepatoma cells
      (MH3924A) by tissue-specific expression of the human sodium/iodide symporter
      (hNIS) gene directed by the murine albumin enhancer and promoter (mAlb). METHODS:
      The cell-specific transcriptional activity of mAlb was examined by a luciferase
      assay in several transiently transfected cell lines. MH3924A cells were stably
      transfected with the recombinant retroviral vector, in which hNIS complementary
      DNA expression was driven by mAlb and coupled to hygromycin resistance gene using
      an internal ribosomal entry site (IRES). Functional hNIS expression in hepatoma
      cells was confirmed by an iodide uptake assay. In imaging studies, the tumor
      bearing ACI rats were intravenously injected with (131)I and imaged with a gamma
      camera. Biodistribution was studied at 30 min and at 1, 3, 6, and 25 h after
      injection of (131)I. Toxic effects of (131)I on hepatoma cells were studied in
      vitro and in vivo. RESULTS: Stably transfected MH3924A cells concentrated (125)I
      up to 240-fold higher than the wild-type cells. The iodide uptake in stably
      transfected cells was inhibited by ouabain and sodium perchlorate but increased
      by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. An in vitro clonogenic assay
      revealed an 86% decrease in colony number in stably transfected cells after
      exposure to 3.7 MBq/mL of (131)I and only about 8% in hNIS-negative control
      cells. Furthermore, the in vivo study showed intense tracer accumulation in hNIS
      expressing tumors after administration of (131)I. At 3 h after intraperitoneal
      injection, the transfected tumors accumulated (131)I 19.2-fold higher than the
      parental tumors in a biodistribution study. Moreover, administration of a
      therapeutic dose of (131)I resulted in an inhibition of hNIS-expressing tumor
      growth, whereas control tumors continued to increase in size. CONCLUSION: A
      therapeutic effect of (131)I on hepatoma cells in vitro and in vivo has been
      demonstrated after tumor-specific iodide uptake induced by mAlb-directed hNIS
      gene expression. Because a stable transformed cell line has been used in these
      experiments, the clinical potential of this strategy must be evaluated after in
      vivo transfection of hepatoma cells.

PMID- 16644757
TI  - A catheter-based intravascular radiation detector of vulnerable plaques.
AB  - Detection of vulnerable plaques before rupture is important in preventing acute
      coronary events such as myocardial infarction. Although therapeutic strategies
      such as percutaneous transluminal coronary angioplasty appear to prevent coronary
      occlusion and consequently may lead to improved prognosis in these patients, a
      method of detecting vulnerable plaques has not been established. A nuclear method
      that uses an intravascular radiation detector (IVRD) with the plaque-avid tracer
      (18)F-FDG is one of the most promising methods. The catheter-based IVRD consists
      of a catheter probe (a scintillator and flexible optic fibers), photomultipliers,
      a controller, and an automatic pullback unit and personal computer. A phantom
      study demonstrated that this detector was highly sensitive to (18)F and enabled
      the detection of (18)F point sources. However, details of the detection system in
      vivo remain unclear. METHODS: To evaluate vulnerable plaques in vivo, we
      investigated a canine femoral artery and coronary artery using this detector
      system. Our goal was to estimate the ability of this device to navigate through
      these arteries and to detect (18)F point sources fixed on their adventitia.
      RESULTS: In the study using a canine femoral artery, the IVRD could detect the
      point sources with good repeatability. In the study using an open-chest canine
      model, the catheter probe could easily be advanced into the left descending
      coronary artery, and the IVRD could detect target sources attached externally to
      the coronary artery (7- to 15-mm intervals) with good resolution. CONCLUSION:
      This newly developed catheter-based IVRD was able to detect, with good
      resolution, the slight radioactivity from (18)F point sources attached to the
      femoral artery and the coronary adventitia. These results show that catheter
      based detection of coronary vulnerable plaques may be feasible.

PMID- 16644758
TI  - Imaging experimental atherosclerotic lesions in ApoE knockout mice: enhanced
      targeting with Z2D3-anti-DTPA bispecific antibody and 99mTc-labeled negatively
      charged polymers.
AB  - In vivo molecular imaging may be improved if specific radioactivity at the target
      site could be increased while maintaining low background activity. Bispecific
      antibody complexes and (99m)Tc-labeled negatively charged chelating polymers that
      react specifically with the capture arm of the bispecific antibody complex were
      used to demonstrate the feasibility of imaging very small atherosclerotic lesions
      in ApoE knockout mice. METHODS: Left femoral artery denudation in ApoE(-/-) mice
      on a hyperlipidemic diet was used to induce accelerated atherosclerotic lesions.
      Approximately 40 microg of bispecific antibodies were injected intravenously
      after 2 wk of endothelial denudation. The next day, approximately 15.0 MBq
      (99m)Tc-DTPA-succinyl-polylysine (2 microg; DTPA is diethylenetriaminepentaacetic
      acid) were injected intravenously. RESULTS: In vivo gamma-images showed that
      lesions were observed unequivocally by 2-3 h. Sham-operated right femoral regions
      showed no radiotracer accumulation. Ex vivo gamma-scintillation counting
      corrected for sham-operated nonspecific activity and lesion mass showed that the
      mean lesion activity was 10.10 +/- 6.76 %ID/g (percentage injected dose per
      gram), whereas nonspecific human IgG bispecific control (NSB control) also
      corrected similarly was 0.939 +/- 0.877 %ID/g (P < 0.03). Atherosclerotic lesions
      were confirmed by immunohistochemical staining. Computer planimetry of
      immunohistograms showed the mean lesion size to be 2.64 +/- 2.46 mg. CONCLUSION:
      Use of bispecific antibody complexes and (99m)Tc-DTPA-succinyl-polylysine enabled
      in vivo visualization of very small atherosclerotic lesions in ApoE knockout
      mice.

PMID- 16644759
TI  - Serial in vivo imaging of the lung metastases model and gene therapy using HSV1
      tk and ganciclovir.
AB  - Noninvasive imaging in lung metastatic tumor models is used infrequently because
      of technical limitations in detecting metastases. We have previously used 2'
      fluoro-2'-deoxy-5-iodo-1-beta-d-arabinofuranosyluracil labeled with (131)I
      ((131)I-FIAU) and demonstrated the applicability of noninvasive imaging for
      monitoring cancer gene therapy in an experimental animal model of herpes simplex
      virus type 1 thymidine kinase (HSV1-tk)-expressing tumor xenografts. We have now
      used the same animal model to effectively and noninvasively monitor the location,
      magnitude, and duration of therapeutic gene expression over time for the lung
      metastases model. METHODS: To improve the detectability of lung metastases, an
      experimental blood-borne lung metastases model in mice was established using
      intravenously administered HSV1-tk-expressing NG4TL4 fibrosarcoma cells (NG4TL4
      TK) and simulated the clinical application of HSV1-tk plus ganciclovir (GCV)
      prodrug activation gene therapy. The efficacy of noninvasively monitoring the
      sites of development of lung metastatic lesions and their GCV-induced regression
      were assessed by SPECT with (131)I-FIAU. RESULTS: The results of this study
      showed that the lung metastases model of NG4TL4-TK cells could be successfully
      detected as early as 24 h after intravenous injection of tumor cells radiolabeled
      with (131)I-FIAU and also subsequently detected by extended monitoring with the
      intravenous injection of (131)I-FIAU on day 10. In mice treated with GCV, gamma
      camera imaging demonstrated a significant growth inhibition of NG4TL4-TK cells of
      primary tumors and lung metastases on day 7 after initiating treatment.
      CONCLUSION: We conclude that this in vivo imaging approach will be useful for
      future studies of the lung metastases model and for the assessment of novel
      anticancer and antimetastatic therapies.

PMID- 16644760
TI  - Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0.

PMID- 16644763
TI  - Alzheimer therapeutics-what after the cholinesterase inhibitors?

PMID- 16644764
TI  - Pharmacodynamic activity of garenoxacin against ciprofloxacin-resistant
      Streptococcus pneumoniae.
AB  - BACKGROUND: The pharmacodynamic parameter that best correlates with
      bacteriological eradication for fluoroquinolones is the free (f) area under the
      24 h serum concentration curve (AUC24) to MIC (fAUC24/MIC) ratio. This study
      assessed garenoxacin fAUC24/MIC against ciprofloxacin-resistant Streptococcus
      pneumoniae using an in vitro pharmacodynamic model. METHODS: A total of 14 S.
      pneumoniae including 1 fluoroquinolone-susceptible and 13 ciprofloxacin-resistant
      S. pneumoniae (ParC, efflux, ParC with efflux, and ParC and GyrA) were studied.
      The quinolone-resistance determining regions (QRDRs) of parC and gyrA were
      sequenced and efflux was assessed using a reserpine assay. S. pneumoniae with
      garenoxacin MICs (mg/L) [number of strains] studied were: 0.03 [1], 0.06 [2],
      0.12 [2], 0.25 [2], 0.5 [3], 1 [2] and 2 [2]. The in vitro pharmacodynamic model
      was inoculated with 1 x 10(6) cfu/mL and garenoxacin was dosed once daily at 0
      and 24 h to simulate fAUC24 and t1/2 obtained after standard oral doses in
      healthy volunteers (400 mg once daily, free AUC24 20 mg.h/L, t1/2 16 h). Sampling
      was performed over 48 h to assess viable growth. RESULTS: Garenoxacin fAUC24/MIC
      achieved in the model ranged from 12 to 800. Garenoxacin fAUC24/MIC 200-800 was
      bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h against ciprofloxacin
      resistant S. pneumoniae mutants including ParC mutants only, efflux mutants only
      and ParC/efflux mutants. Garenoxacin fAUC24/MIC 48-96 was bactericidal (> or = 3
      log(10) killing) at 24 and 48 h against all ciprofloxacin-resistant S. pneumoniae
      mutants. Garenoxacin fAUC24/MIC < or = 24 (against ParC and GyrA mutants)
      resulted in a bacteriostatic effect with regrowth at 24 and 48 h. CONCLUSIONS:
      Garenoxacin was bactericidal against ciprofloxacin-resistant S. pneumoniae at
      fAUC24/MIC > or = 48. Garenoxacin fAUC24/MIC < or = 24 resulted in a
      bacteriostatic effect with regrowth at 24 and 48 h.

PMID- 16644765
TI  - Improving depression outcome: new concepts, strategies and technologies.

PMID- 16644766
TI  - Remission in depression: definition and initial treatment approaches.
AB  - Although remission is recognized as the optimal outcome of treatment for
      depression, remission lacks a universally accepted definition. This is partly due
      to the lack of objective biologic markers or tests that confirm a response to
      treatment and no well-defined end points of treatment. Significant symptoms may
      still exist even though patients may have a full response as measured by
      currently available standardized psychiatric rating scales. In addition, many
      patients may experience marked improvement in depressive symptoms but still have
      impaired psychosocial and work function. Wellness should be determined by
      evaluating a combination of three key domains: symptoms, functional status and
      pathophysiologic changes. In choosing an initial medication for depression,
      physicians are often guided by a mix of evidence-based medicine and unvalidated
      or even inaccurate clinical lore. In general, most available agents have
      comparable effectiveness; however, the subtype of depression and age of the
      patient should be considered.

PMID- 16644767
TI  - Augmentation and combination strategies for depression.
AB  - Treatment-resistant depression represents a common problem, with the vast
      majority of depressed patients showing incomplete response to antidepressant
      trials. Augmentation and combination strategies are commonly employed to address
      this problem, but there are few randomized, controlled studies to guide treatment
      choice. Indeed, some of the most common augmentation strategies in depression are
      those with the least controlled evidence. The popularity of bupropion,
      psychostimulants and atypical antipsychotics as augmentors may not be warranted
      by existing controlled studies, whereas two less commonly used augmentors-lithium
      and thyroid hormone- have substantial controlled evidence to support their use.
      This paper summarizes the state of the evidence for commonly used augmenting
      strategies and explores preliminary findings for more investigational approaches.

PMID- 16644768
TI  - Enhancing the efficacy of antidepressants with psychotherapy.
AB  - Even after optimal treatment with and response to antidepressant medications
      during acute treatment of major depressive disorder, residual symptoms are
      common. Patients with residual symptoms are at increased risk of relapse and
      recurrence. Research suggests that psychotherapy may play an important role in
      enhancing the effects of antidepressant drug therapy and improving patients' long
      term prognosis. Psychotherapy targets specific symptoms associated with relapse
      (e.g., guilt, hopelessness, negativity, low self-esteem) that antidepressants may
      not, reduces residual symptoms (e.g., irritability), improves coping skills for
      long-term disease management and promotes sustained, healthy cognitive changes.
      In addition, neuroimaging data suggest that psychotherapy and pharmacotherapy
      target different primary sites of the cortical-limbic pathway with differential
      top-down and bottom-up effects, resulting in modulation of critical common
      targets and facilitation of disease remission. The use of adjunctive
      psychotherapy in the acute phase of depression treatment appears to provide only
      a modest increase in response rates, although combined pharmaco-psychotherapy may
      prevent or delay relapse. Simultaneous application of pharmacotherapy and
      psychotherapy during the maintenance phase does not consistently provide a clear
      advantage over maintenance pharmacotherapy. In contrast, sequential use of
      psychotherapy after induction of remission with acute antidepressant drug therapy
      may confer a better long-term prognosis in terms of preventing relapse or
      recurrence and, for some patients, may be a viable alternative to maintenance
      medication therapy.

PMID- 16644769
TI  - Pharmacological approaches to the treatment of residual symptoms.
AB  - Despite the efficacy of currently available antidepressant treatment, residual
      symptoms are common among individuals treated for major depressive disorder and
      are associated with an increased risk of relapse and poor psychosocial
      functioning. However, distinguishing treatment-emergent side effects from
      residual symptoms can be challenging for clinicians. Anxiety, sleep disturbance,
      somnolence/fatigue, apathy and cognitive dysfunction are among the more frequent
      residual symptoms. Approaches to the management of residual symptoms include
      addressing treatment-emergent side effects and co-morbid conditions, optimizing
      antidepressant dosing and using augmentation therapy. Clinicians are often guided
      in their decisions by anecdotal impressions. Studies assessing the evaluation and
      treatment of residual symptoms and side effects will contribute importantly to
      the optimal acute and long-term management of depression.

PMID- 16644770
TI  - Neurostimulation in resistant depression.
AB  - Drugs and psychotherapy are inadequate for relieving depressive symptoms in a
      substantial portion of severely depressed patients. In that patient group,
      neurostimulation techniques such as electroconvulsive therapy, transcranial
      magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation and deep
      brain stimulation could be lifesaving therapies. Neurostimulation is a physical
      intervention that utilizes application of either electric current or a magnetic
      field to directly stimulate the brain or central nervous system. This article
      presents an overview of currently available neurostimulatory techniques for
      depression, including a review of their efficacy and safety. Further development
      and evaluation of non-pharmacological antidepressant therapies are needed, with
      the hope of improving treatment of refactory depression.

PMID- 16644771
TI  - A Friday afternoon case of apparent anti-glomerular basement nephritis.

PMID- 16644772
TI  - Complete renal tubular acidosis late after kidney transplantation.
AB  - BACKGROUND: Neither the prevalence nor the associated risk factors of late post
      transplant renal tubular acidosis (RTA) are known. METHODS: We conducted a cross
      sectional study with 576 patients for more than 12 months after kidney
      transplantation, and a glomerular filtration rate (GFR) >40 ml/min. RTA was
      diagnosed by measurement of the urine anionic gap, urine pH and plasma potassium
      during acidosis, and fractional bicarbonate excretion after bicarbonate loading.
      Uni- and multi-variable analysis were used to isolate factors associated with
      post-transplant RTA, and with the different RTA subtypes. RESULTS: All patients
      (n = 76) had distal post-transplant RTA. A significant association with the
      presence of RTA was found for the intake of tacrolimus or renin-angiotensin
      aldosterone blockers, the Parathyroid hormone level and the GFR. Type Ia
      (classic, distal), type Ib (hyperkalaemic, voltage-dependent), rate-limited and
      type IV RTA were present in 37, 14, 21 and 28% of the patients. Acute transplant
      rejection was the only significant different parameter between the RTA subtypes
      and more often present in patients with type Ia or Ib RTA. CONCLUSIONS: We
      conclude that a significant fraction of stable long-term renal transplant
      recipients with adequate graft function develop post-transplant RTA, with a
      preponderance for type Ia and type IV, and absence of type II. In addition, acute
      transplant rejection seems to have an influence on the subtype of RTA present
      post-transplantation.

PMID- 16644773
TI  - Immunohistochemical evidence of activated lectin pathway in kidney allografts
      with peritubular capillary C4d deposition.
AB  - BACKGROUND: Complement 4d (C4d) deposition in the peritubular capillary (PTC) in
      the kidney allograft is a useful diagnostic marker for humoral rejection. C4d is
      produced not only by the classical pathway but also by the lectin pathway of the
      complement activation cascade. We have recently reported the in situ role of the
      later phase of the complement cascade in renal allografts with C4d deposition;
      however, the initial process prior to C4d deposition is yet to be resolved.
      METHODS: To clarify the early phases of the complement activation cascade, we
      evaluated the deposition of initial proteins of the above two pathways; IgG, IgM,
      mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine
      protease (MASP)-1 and MASP-2 in kidney allografts with PTC C4d deposition.
      RESULTS: Sixty kidney allograft specimens were divided into two groups on the
      basis of the presence of C4d deposition in PTC. The C4d-positive group (n = 18)
      included nine ABO-identical and nine ABO-incompatible cases, and the C4d-negative
      group (n = 42) had 34 ABO-identical and eight ABO-compatible (but not identical)
      cases. In the C4d-positive group, 16 of 18 cases showed diffuse H-ficolin and IgM
      deposition in PTC. In contrast, H-ficolin and IgM were not detected in PTC in the
      C4d-negative group. Other initial proteins were not detected in all cases.
      CONCLUSIONS: Our study suggested for the first time that the lectin pathway
      activated by H-ficolin may be involved in C4d deposition on PTC in the kidney
      allograft.

PMID- 16644774
TI  - Discontinuation of immunosuppression in proliferative lupus nephritis: is it
      possible?

PMID- 16644775
TI  - Fetuin-A and kidney function in persons with coronary artery disease--data from
      the Heart and Soul Study.
AB  - BACKGROUND: Fetuin-A is a serum protein that inhibits ectopic vascular
      calcification and is present in lower concentrations in end-stage renal disease
      than in healthy controls. Whether fetuin-A concentrations are also lower in the
      setting of mild-to-moderate chronic kidney disease (CKD) is unknown. METHODS: We
      evaluated the associations of several parameters of kidney function including
      measured 24 h urinary creatinine clearance (CrCl), estimated glomerular
      filtration rate (GFR) by the Mayo Clinic quadratic GFR equation (qGFR), serum
      cystatin-C concentrations, and urinary albumin-to-creatinine ratio with serum
      fetuin-A concentrations in 970 outpatients with coronary artery disease. We used
      general linear models to determine the adjusted mean fetuin-A concentrations
      within each kidney function category. RESULTS: The mean age of the study sample
      was 67 years, 82% were male, 71% had hypertension and 26% had diabetes mellitus.
      In adjusted analysis, we observed no significant differences in mean fetuin-A
      concentrations across groups defined by CrCl, qGFR, or albumin-to-creatinine
      ratio groups. For example, adjusted mean fetuin-A concentrations were 0.66 g/l in
      participants with CrCl > 90, 60-90 and 45-60 ml/min/1.73 m(2), and 0.65 g/l in
      participants with CrCl < 45 ml/min/1.73 m(2). Higher serum cystatin-C (indicating
      worse kidney function) was associated with higher adjusted mean serum fetuin-A
      concentrations (lowest quartile 0.62 g/l, highest quartile 0.68 g/l; P for trend
      <0.001). CONCLUSIONS: Among ambulatory patients with coronary artery disease,
      there is no evidence that mild-to-moderate CKD is associated with lower
      concentrations of serum fetuin-A compared with persons with normal renal
      function. The mechanisms explaining the association between CKD and vascular
      calcification remain elusive.

PMID- 16644776
TI  - Detection of donor-specific antibodies using HLA-coated microspheres: another
      tool for kidney transplant risk stratification.
AB  - BACKGROUND: Sensitive techniques are able to detect low levels of circulating
      antibodies. For many newer techniques, the clinical consequences of these
      antibodies are unknown. We hoped to determine the significance of antibodies
      detected through the use of Luminex microsphere-based assay. METHODS: Patients
      who received kidney transplants between March 2003 and May 2004 with negative
      anti-human globulin-augmented complement-dependent cytotoxicity (AHG-CDC)
      crossmatches were retested for pre-transplant panel reactive antibodies (PRA)
      using Luminex microspheres and stored sera. Patients were considered to have
      circulating antibodies if either class I or class II Luminex PRA was >or=15%.
      These patients were then analysed for pre-transplant donor-specific antibodies
      (DSA). Clinical outcomes were compared in patients with and without DSAs.
      RESULTS: Out of 136 patients who underwent transplantation, 55 had Luminex PRA
      >or=15%. Of these 55 patients, only 16 had a standard PRA >or=30% and 75% had a
      history of a sensitizing event. Twenty out of 55 patients were DSA+. Patients
      with DSA detected by Luminex had higher rates of primary non-function (PNF),
      delayed graft function, biopsy-proven acute rejection, and lower rates of graft
      survival at 6 months. A combined endpoint of immunological and clinical events
      was far more common in patients with DSA. CONCLUSION: The detection of DSAs by
      Luminex microspheres was associated with significantly higher rates of graft
      dysfunction and immunological events. Conversely, the presence of antibodies but
      no DSA by Luminex was associated with excellent outcomes. In patients with
      negative AHG-CDC crossmatches, the occurrence of low-level DSA by Luminex could
      assist in identifying patients that require more aggressive immune monitoring or
      immunosuppressive strategies.

PMID- 16644777
TI  - Renal function and 25-hydroxyvitamin D concentrations predict parathyroid hormone
      levels in renal transplant patients.
AB  - BACKGROUND: Recent guidelines suggest supplementation with ergocalciferol
      (vitamin D(2)) in chronic kidney disease stages 3 and 4 patients with elevated
      parathyroid hormone (PTH) levels and 25-hydroxyvitamin D (25OHD) levels <75
      nmol/l. These guidelines are also applied to renal transplant patients. However,
      the prevalence rates of 25OHD deficiency and its association with PTH levels in
      renal transplant populations have not been extensively examined. We aimed to
      document the prevalence rates of 25OHD deficiency [defined by serum levels <40
      nmol/l (<16 ng/ml)] and insufficiency [<75 nmol/l (<30 ng/ml)] in a single renal
      transplant centre, and examine its relationship with PTH levels. METHODS: Serum
      25OHD and PTH concentrations were measured in 419 transplant patients attending a
      single renal transplant clinic over a 4-month period. Demographic and biochemical
      data were also collected, including serum creatinine, calcium, phosphate and
      albumin. Simple and multiple linear regression analysis were performed. RESULTS:
      In 27.3% of the patients, 25OHD deficiency was present, and 75.5% had
      insufficiency. On univariate analysis, 25OHD, serum albumin and estimated
      glomerular filtration rate (eGFR) were significantly associated with PTH levels
      (P < 0.0001, P = 0.004 and P < 0.0001, respectively). Multiple linear regression
      demonstrated that only 25OHD, eGFR and serum phosphate were significantly
      predictive of PTH levels (R(2) = 0.19, P < 0.0001). In this model, a 75 nmol/l
      increase in 25OHD will only result in a maximal reduction in PTH of 2.0 pmol/l.
      CONCLUSIONS: We conclude that 25OHD deficiency and insufficiency are common in
      renal transplant patients and may exacerbate secondary hyperparathyroidism.
      However, 25OHD, eGFR and phosphate only account for 19% of the variability in PTH
      levels. In addition, even a large increase in serum 25OHD levels is likely to
      result in only a small reduction in PTH. Therefore, alternative approaches to
      managing hyperparathyroidism in renal transplant recipients rather than
      supplementation with ergocalciferol are warranted.

PMID- 16644778
TI  - Mortality risk factors in chronic haemodialysis patients with infective
      endocarditis.
AB  - BACKGROUND: It is well documented that infective endocarditis (IE) is strongly
      associated with morbidity and mortality in haemodialysis (HD) patients. Less
      clear are the mortality risk factors for IE, particularly in an urban African
      American dialysis population. METHODS: IE patients were identified from the
      medical records for the period from January 1999 to February 2004 and confirmed
      by Duke criteria. The patients were classified as 'survivors' and 'non-survivors'
      depending on in-hospital mortality, and risk factors for IE mortality were
      determined by comparing the two cohorts. Survivors were followed as out-patients
      with death as the endpoint. RESULTS: A total of 52 patients with 54 episodes of
      IE were identified. A catheter was the HD access in 40 patients (74%). Mitral
      valve (50%) was the commonest valve involved, and Gram-positive infections
      accounted for 87% of IE. In-hospital mortality was high (37%) and valve
      replacement was required for 13 IE episodes (24%). On logistic regression
      analyses, mitral valve disease [P = 0.002; odds ratio (OR) = 15.04; 95%
      confidence interval (CI) = 2.70-83.61] and septic embolism (P = 0.0099; OR =
      9.56; 95% CI = 1.72-53.21) were significantly associated with in-hospital
      mortality. Using the Cox proportional hazards model, mitral valve involvement (P
      = 0.0008; hazard ratio 4.05; 95% CI = 1.78-9.21) and IE related to drug-resistant
      organisms such as methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococcus sp. (P = 0.016; hazard ratio 2.43; 95% CI = 1.18-5.00)
      were associated with poor outcome after hospital discharge. CONCLUSIONS: IE was
      associated with high mortality in our predominantly African-American dialysis
      population, when the mitral valve was involved, or septic emboli occurred and if
      MRSA or VRE were the causal organisms.

PMID- 16644779
TI  - Decline in kidney function before and after nephrology referral and the effect on
      survival in moderate to advanced chronic kidney disease.
AB  - BACKGROUND: The burden of chronic kidney disease (CKD) is high, but its natural
      history and the benefit of routine nephrology care is unclear. This study
      investigated the decline in kidney function prior to and following nephrology
      referral and its association with mortality. METHODS: This study provides a
      retrospective review of the individual rates of glomerular filtration rate (GFR)
      decline (millilitre per minute per 1.73 m(2)/year) for the 5 years before and
      after referral in 726 new referrals with stages 3-5 CKD to one renal unit between
      1997 and 2003. Blood pressures are averages at referral, 1 and 3 years post
      referral. Logistic regression and Cox's models tested factors predicting post
      referral GFR decline and the impact on mortality. RESULTS: Mean (SD) age was 72
      (14), and 389 (54%) patients had stages 4-5 CKD. GFR decline slowed significantly
      from -5.4 ml/min/1.73 m(2)/year (-13. to -2) before to -0.35 ml/min/1.73
      m(2)/year (-3 to +3) after referral (P < 0.001). Blood pressure also reduced
      significantly (155/84 to 149/80, P < 0.05) with most changes occurring within 1
      year of referral. Factors predicting a non-progressive post-referral decline
      included a lower systolic blood pressure at referral and 1 year after referral, a
      CKD diagnosis other than diabetic nephropathy, less baseline proteinuria and a
      non-progressive pre-referral GFR decline. A non-progressive post-referral GFR
      decline was independently associated with significantly better survival (hazard
      ratio 0.55, 95% CI 0.40-0.75, P <or = 0.001) after adjustment for known risk
      factors. CONCLUSIONS: Following nephrology referral, GFR decline slowed
      significantly and was associated with better survival. Earlier detection of
      patients with progressive CKD and interventions to slow progression may have
      benefits on both kidney and patient survival.

PMID- 16644780
TI  - Public-private partnership in Hungarian dialysis care.

PMID- 16644781
TI  - Remission of polyomavirus-induced graft nephropathy treated with low-dose
      leflunomide.

PMID- 16644782
TI  - Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly
      onset rheumatoid arthritis.
AB  - BACKGROUND: Polymyalgia rheumatica (PMR) may create some difficulties in the
      differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA
      with PMR-like onset (EORA/PMR). AIM: To investigate possible differences between
      three groups of patients, with regard to serum levels of inflammatory cytokines
      and steroidal hormones at baseline and after 1 month of treatment with
      glucocorticoids (prednisone 7.5-12.5 mg/day). PATIENTS AND METHODS: 14 patients
      with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched
      controls were analysed. Tumour necrosis factor alpha (TNFalpha), interleukin
      (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate
      (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. RESULTS: Serum levels
      of both TNFalpha and IL6 were significantly higher in all three groups of
      patients than in controls (p<0.01). Serum IL6 levels were significantly higher in
      patients with both PMR and EORA/PMR than in patients with EORA (p<0.05). IL1Ra
      serum levels were significantly higher in patients with EORA than in controls
      (p<0.001) and in patients with PMR and EORA/PMR (p<0.05). DHEAS was significantly
      lower in patients with EORA/PMR than in those with EORA (p<0.05). PRG was
      significantly higher in all patient groups (p<0.05). After glucocorticoid
      treatment, serum TNFalpha and IL6 levels significantly decreased in all patient
      groups; IL1Ra significantly increased in patients with PMR and in those with
      EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR
      and in those with EORA/PMR (p<0.05). CONCLUSIONS: Different cytokine and
      steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR
      seem to be have a more intensive inflammatory reaction and are more efficient
      responders to glucocorticoid treatment than patients with EORA.

PMID- 16644783
TI  - Performance of response criteria for assessing peripheral arthritis in patients
      with psoriatic arthritis: analysis of data from randomised controlled trials of
      two tumour necrosis factor inhibitors.
AB  - BACKGROUND: In recent clinical trials in patients with psoriatic arthritis (PsA),
      the response criteria and disease activity measures that have been used were
      those developed for rheumatoid arthritis. However, these have not yet been
      validated in PsA. OBJECTIVE: To compare the responsiveness and discriminative
      capacity of the psoriatic arthritis response criteria (PsARC), American College
      of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response
      criteria and the Disease Activity Score (DAS) and core-set measures in patients
      with PsA and peripheral arthritis, using the data from two randomised placebo
      controlled trials of tumour necrosis factor inhibitors. METHODS: In an infliximab
      trial, 104 patients with active PsA were randomised to receive placebo or
      infliximab for 16 weeks. In an etanercept trial, 60 patients with active PsA were
      randomised to receive placebo or etanercept for 12 weeks. Data from baseline and
      the end of the intervention phase were used from each study. Responsiveness was
      assessed using the standardised response mean and effect size. Capacity to
      discriminate between the active drug and placebo was assessed using t values or a
      chi2 test. Measures were ranked in order of their t value or chi2 value. RESULTS:
      The EULAR criteria performed better in discriminating the active drug from
      placebo than the ACR20 improvement criteria, which in turn performed better than
      the PsARC. It was also found that the pooled indices (DAS and DAS28) were
      generally more responsive, and performed better in discriminating active drug
      from placebo, than the single core-set measures. CONCLUSION: Response criteria
      and pooled indices developed for rheumatoid arthritis are useful for the
      assessment of arthritis in PsA clinical trials.

PMID- 16644784
TI  - Sex differences in gout epidemiology: evaluation and treatment.
AB  - BACKGROUND: Little is known about the characteristics, evaluation and treatment
      of women with gout. OBJECTIVE: To examine the epidemiological differences and
      differences in treatment between men and women in a large patient population.
      METHODS: The data from approximately 1.4 million people who were members of seven
      managed care plans in the USA for at least 1 year between 1 January 1999 and 31
      December 2003 were examined. Adult members who had pharmacy benefits and at least
      two ambulatory claims specifying a diagnosis of gout were identified. In
      addition, men and women who were new users of urate-lowering drugs (ULDs) were
      identified to assess adherence with recommended surveillance of serum urate
      levels within 6 months of initiating urate-lowering treatment. RESULTS: A total
      of 6133 people (4975 men and 1158 women) with two or more International
      Classification of Disease-9 codes for gout were identified. As compared with men
      with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had
      comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of
      new users of urate-lowering treatment had appropriate surveillance of serum urate
      levels post-initiation of urate-lowering treatment. After controlling for age,
      comorbidities, gout treatments, number of ULD dispensings and health plan, women
      were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to
      receive the recommended serum urate level testing. CONCLUSIONS: Women with gout
      were older, had greater comorbidities and more often used diuretics and received
      appropriate surveillance of serum urate levels, suggesting that the factors
      leading to gout as well as monitoring of treatment are very different in women
      and men.

PMID- 16644785
TI  - Increased disease activity is associated with a deteriorated lipid profile in
      patients with ankylosing spondylitis.
AB  - BACKGROUND: Cardiovascular mortality is increased in patients with ankylosing
      spondylitis. A possible explanation might be a more prevalent atherogenic lipid
      profile in patients with ankylosing spondylitis than in the general population.
      It has been postulated that inflammation deteriorates the lipid profile, thereby
      increasing cardiovascular risk. OBJECTIVE: To explore the association between
      disease activity and lipid profile in patients with ankylosing spondylitis.
      METHODS: Disease activity parameters for ankylosing spondylitis and lipid levels
      (total cholesterol, high-density lipoprotein cholesterol (HDLc) and
      triglycerides) were measured in 45 patients with ankylosing spondylitis for 6
      months after starting treatment with leflunomide or placebo. Findings in this
      treatment group were compared with those in 10 patients with ankylosing
      spondylitis treated with etanercept. A specialised regression model, adjusting
      for repeated measurements, age and sex, was used to assess the influence of the
      disease activity variables on the lipid levels. RESULTS: Multilevel regression
      analyses showed significant associations between disease activity parameters and
      lipid levels-for instance, an increase of 30 mm at the end of the first hour in
      erythrocyte sedimentation rate was associated with a decrease of about 6% in
      total cholesterol level and a decrease of about 11% in HDLc levels. Similar
      significant associations were found between other disease activity parameters and
      lipid levels. CONCLUSION: Increase in disease activity was associated with
      decreases in lipid levels. The decrease in HDLc levels tended to be almost twice
      as large as the decrease in total cholesterol levels, resulting in a more
      atherogenic lipid profile. Hence, effective treatment of disease activity in
      patients with ankylosing spondylitis may lower the cardiovascular risk by
      improving the lipid profile.

PMID- 16644786
TI  - Radiation synovectomy with yttrium-90 for persisting arthritis has direct harmful
      effects on human cartilage that cannot be prevented by co-administration of
      glucocorticoids: an in vitro study.
AB  - BACKGROUND: It was recently shown that radiation synovectomy with yttrium-90
      (90Y) and glucocorticoids is not superior to intra-articular glucocorticoids
      alone in the treatment of persistent gonarthritis. In that study, it seemed that
      in patients treated by radiation synovectomy, progression of radiographic joint
      damage occurred. OBJECTIVE: To test in vitro the direct effects of radiation
      synovectomy with 90Y on human cartilage. METHODS: Human cartilage tissue was
      exposed to 90Y, glucocorticoids or the combination. 1:2000 to 1:20 dilutions of
      the clinical dose of 5 mCi/ml 90Y and 20 mg/ml glucocorticoids were used. After a
      4-day exposure and a subsequent 12-day recovery period, proteoglycan synthesis,
      proteoglycan release and proteoglycan content were measured. In addition, human
      synovial tissue was cultured for 4 days with 90Y or glucocorticoids. Culture
      supernatants were analysed for cartilage-destructive activity. RESULTS: 90Y,
      glucocorticoids and the combination inhibited proteoglycan synthesis considerably
      and dose dependently, an effect that sustained for at least 12 days. Proteoglycan
      release was transiently increased by 90Y, an effect that was not changed by
      addition of glucocorticoids, which had no effect on its own. Proteoglycan content
      was eventually adversely affected by 90Y, an effect hardly influenced by
      glucocorticoids. Neither 90Y nor glucocorticoids changed the cartilage
      destructive properties of synovial tissue. CONCLUSIONS: 90Y, but not
      glucocorticoids, has direct harmful effects on cartilage in vitro. Indirect
      beneficial effects of 90Y via inhibition of cartilage-destructive properties of
      synovial tissue could not be shown. These observations may explain the possible
      radiographic joint damage on radiation synovectomy.

PMID- 16644787
TI  - Transcriptional expression of survivin and its splice variants in endometriosis.
AB  - Survivin is a novel inhibitor of apoptosis (IAP), and the two splice variants of
      survivin (survivin-2B and survivin-EX3) have been identified. Gene expression
      levels of survivin, survivin-2B and survivin-EX3 in 56 ectopic (16 peritoneal red
      and 16 peritoneal black lesions and 24 ovarian endometriomata) and 13 eutopic
      endometrial tissues surgically obtained from 42 women with endometriosis (group
      A) were compared with those in 16 control eutopic endometrium from 16 women
      without endometriosis (group B) by quantitative RT-PCR analysis. Survivin mRNA
      expression levels in ectopic endometriotic tissues were significantly higher than
      those in eutopic endometrium of groups A and B over the whole cycle. Red
      peritoneal lesions had higher gene expression levels of survivin than black
      lesions. In contrast, all tissue samples examined showed relatively lower gene
      expression levels of survivin-2B and survivin-EX3. No cyclic variation was found
      in survivin and the two splice variants, both in ectopic and in eutopic
      endometrium. Although there was no significant difference in the ratio of
      survivin-2B/survivin between ectopic and eutopic endometrium, the ratio of
      survivin-EX3/survivin in peritoneal endometriotic lesions was significantly
      higher than that of eutopic endometrium of groups A and B. These results suggest
      that survivin and survivin-EX3 may be closely linked to escape from apoptosis and
      the development of endometriosis.

PMID- 16644788
TI  - Identification of humoral immune responses in protein microarrays using DNA
      microarray data analysis techniques.
AB  - MOTIVATION: We present a study of antigen expression signals from a newly
      developed high-throughput protein microarray technique. These signals are a
      measure of antibody-antigen binding activity and provide a basis for
      understanding humoral immune responses to various infectious agents and
      supporting vaccine and diagnostic development. RESULTS: We investigate the
      characteristics of these expression profiles and show that noise models,
      normalization, variance estimation and differential expression analysis
      techniques developed in the context of DNA microarray analysis can be adapted and
      applied to these protein arrays. Using a high-dimensional dataset containing
      measurements of expression profiles of antibody reactivity against each protein
      (295 antigens and 9 controls) in 42 malaria (Plasmodium falciparum) protein
      arrays derived from 22 donors with various clinical presentations of malaria, we
      present a methodology for the analysis and identification of significantly
      expressed antigens targeted by immune responses for individual sera, groups of
      sera and across stages of infection. We also conduct a short study highlighting
      the top immunoreactive antigens where we identify three novel high priority
      antigens for future evaluation. AVAILABILITY: All software programs (in R) used
      for the analysis described in this paper are freely available for academic
      purposes at www.igb.uci.edu/servers/servers.html.

PMID- 16644789
TI  - Method for identifying transcription factor binding sites in yeast.
AB  - MOTIVATION: Identifying transcription factor binding sites (TFBSs) is helpful for
      understanding the mechanism of transcriptional regulation. The abundance and the
      diversity of genomic data provide an excellent opportunity for identifying TFBSs.
      Developing methods to integrate various types of data has become a major trend in
      this pursuit. RESULTS: We develop a TFBS identification method, TFBSfinder, which
      utilizes several data sources, including DNA sequences, phylogenetic information,
      microarray data and ChIP-chip data. For a TF, TFBSfinder rigorously selects a set
      of reliable target genes and a set of non-target genes (as a background set) to
      find overrepresented and conserved motifs in target genes. A new metric for
      measuring the degree of conservation at a binding site across species and methods
      for clustering motifs and for inferring position weight matrices are proposed.
      For synthetic data and yeast cell cycle TFs, TFBSfinder identifies motifs that
      are highly similar to known consensuses. Moreover, TFBSfinder outperforms well
      known methods. AVAILABILITY: http://cg1.iis.sinica.edu.tw/~TFBSfinder/.

PMID- 16644790
TI  - An online literature mining tool for protein phosphorylation.
AB  - A web-based version of the RLIMS-P literature mining system was developed for
      online mining of protein phosphorylation information from MEDLINE abstracts. The
      online tool presents extracted phosphorylation objects (phosphorylated proteins,
      phosphorylation sites and protein kinases) in summary tables and full reports
      with evidence-tagged abstracts. The tool further allows mapping of phosphorylated
      proteins to protein entries in the UniProt Knowledgebase based on PubMed ID
      and/or protein name. The literature mining, coupled with database association,
      allows retrieval of rich biological information for the phosphorylated proteins
      and facilitates database annotation of phosphorylation features.

PMID- 16644791
TI  - How accurately can we control the FDR in analyzing microarray data?
AB  - SUMMARY: We want to evaluate the performance of two FDR-based multiple testing
      procedures by Benjamini and Hochberg (1995, J. R. Stat. Soc. Ser. B, 57, 289-300)
      and Storey (2002, J. R. Stat. Soc. Ser. B, 64, 479-498) in analyzing real
      microarray data. These procedures commonly require independence or weak
      dependence of the test statistics. However, expression levels of different genes
      from each array are usually correlated due to coexpressing genes and various
      sources of errors from experiment-specific and subject-specific conditions that
      are not adjusted for in data analysis. Because of high dimensionality of
      microarray data, it is usually impossible to check whether the weak dependence
      condition is met for a given dataset or not. We propose to generate a large
      number of test statistics from a simulation model which has asymptotically (in
      terms of the number of arrays) the same correlation structure as the test
      statistics that will be calculated from the given data and to investigate how
      accurately the FDR-based testing procedures control the FDR on the simulated
      data. Our approach is to directly check the performance of these procedures for a
      given dataset, rather than to check the weak dependency requirement. We
      illustrate the proposed method with real microarray datasets, one where the
      clinical endpoint is disease group and another where it is survival.

PMID- 16644792
TI  - Evolutionary trace report_maker: a new type of service for comparative analysis
      of proteins.
AB  - : Evolutionary trace report_maker offers a new type of service for researchers
      investigating the function of novel proteins. It pools, from different sources,
      information about protein sequence, structure and elementary annotation, and to
      that background superimposes inference about the evolutionary behavior of
      individual residues, using real-valued evolutionary trace method. As its only
      input it takes a Protein Data Bank identifier or UniProt accession number, and
      returns a human-readable document in PDF format, supplemented by the original
      data needed to reproduce the results quoted in the report.

PMID- 16644793
TI  - Map2mod--a server for evaluation of crystallographic models and their agreement
      with electron density maps.
AB  - Here we report on recent developments of the map2mod server. It has been designed
      for validation of protein models created by X-ray data interpretation. It can
      also be used during the refinement process since it is able to indicate problem
      regions in the model. Apart from evaluation of model quality, it has an option to
      remove atoms of side chains, which are not consistent with the maps as well as
      improperly placed water molecules. There are two additional options: checking the
      B-factors of atoms in the provided model and comparison of R and R(free) values
      obtained as the result of refinement with the averages characteristic for the
      data resolution shell.

PMID- 16644794
TI  - Mifepristone (RU38486) influences the core temperature response of term pregnant
      rats to intraperitoneal lipopolysaccharide.
AB  - Pregnancy alters the cytokine, prostanoid and core temperature responses of rats
      to infectious stimuli at a time when blood levels of the endogenous
      glucocorticoid corticosterone are elevated. Given that glucocorticoids attenuate
      bacterial pyrogen-induced fever in rats, the present experiments were carried out
      to test the hypothesis that administration of RU38486, a glucocorticoid type II
      receptor antagonist, would restore the febrile response to E. coli
      lipopolysaccharide (LPS) in pregnant rats on day 21 of gestation. Pregnant rats
      were randomly allocated to one of four experimental groups depending upon whether
      they received RU38486 (20 mg kg(-1) intragastric) or vehicle followed by E. coli
      LPS (160 microg kg(-1)i.p.; a minimal dose that elicits maximal febrile response
      in non-pregnant rats) or vehicle. Basal core temperature was not altered by
      intragastric administration of RU38486 or vehicle. Following intragastric
      administration of vehicle, intraperitoneal administration of E. coli LPS produced
      a significant hypothermia with latency, duration and magnitude of 0.5 h, 2 h and 
      1.3 degrees C, respectively. Following intragastric administration of RU38486,
      however, intraperitoneal administration of E. coli LPS elicited only a minimal
      decrease in core temperature which was not significantly different from control
      values. Thus, our data provide evidence that endogenous glucocorticoids play a
      role in modulating the early core temperature response to a relatively large dose
      of bacterial pyrogen in rats at term of pregnancy.

PMID- 16644795
TI  - Forearm vascular responses to combined muscle metaboreceptor activation in the
      upper and lower limbs in humans.
AB  - Our previous studies showed that venous occlusion or passive stretch of the lower
      limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non
      exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb.
      In this study, we investigated whether a metabolic stimulus to the lower limb
      induces a similar response. Eight subjects performed a 2 min static handgrip
      exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the
      upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30%
      MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb
      alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non
      exercised arm decreased significantly, whereas during combined PEMI of the upper
      and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb
      was attenuated. Forearm blood flow and FVC were significantly greater during
      combined PEMI of the upper and lower limbs than during PEMI of the upper limb
      alone. When PEMI of the lower limb was released after combined PEMI of the upper
      and lower limbs (only PEMI of the upper limb was maintained continuously), the
      attenuated decreases in FBF and FVC observed during combined PEMI of the upper
      and lower limbs was not observed. Thus, forearm vascular responses differ when
      muscle metaboreceptors are activated in the upper limb and when there is combined
      activation of muscle metaboreceptors in both the upper and lower limbs.

PMID- 16644796
TI  - Effect of dopamine on rat diaphragm apoptosis and muscle performance.
AB  - The purpose of this study was to determine whether dopamine (DA) decreases
      diaphragm apoptosis and attenuates the decline in diaphragmatic contractile
      performance associated with repetitive isometric contraction using an in vitro
      diaphragm preparation. Strenuous diaphragm contractions produce free radicals and
      muscle apoptosis. Dopamine is a free radical scavenger and, at higher
      concentrations, increases muscle contractility by simulating beta2
      adrenoreceptors. A total of 47 male Sprague-Dawley rats weighing 330-450 g were
      used in a prospective, randomized, controlled in vitro study. Following animal
      anaesthetization, diaphragms were excised, and muscle strips prepared and placed
      in a temperature-controlled isolated tissue bath containing Krebs-Ringer solution
      (KR) or KR plus 100 microm DA. The solutions were equilibrated with oxygen (O2)
      at 10, 21 or 95% and 5% carbon dioxide, with the balance being nitrogen.
      Diaphragm isometric twitch and subtetanic contractions were measured
      intermittently over 65 min. The diaphragms were then removed and, using a nuclear
      differential dye uptake method, the percentages of normal, apoptotic and necrotic
      nuclei were determined using fluorescent microscopy. There were significantly
      fewer apoptotic nuclei in the DA group diaphragms than in the KR-only group
      diaphragms in 10 and 21% O2 following either twitch or subtetanic contractions.
      Dopamine at 100 microm produced only modest increases in muscle performance in
      both 10 and 21% O2. The attenuation of apoptosis by DA was markedly greater than
      the effect of DA on muscle performance. Dopamine decreased diaphragmatic
      apoptosis, perhaps by preventing the activation of intricate apoptotic pathways,
      stimulating antiapoptotic mechanisms and/or scavenging free radicals.

PMID- 16644797
TI  - CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+
      channels in the rat and mouse thalamus.
AB  - Although T-type Ca(2+) channels in the thalamus play a crucial role in
      determining neuronal excitability and are involved in sensory processing and
      pathophysiology of epilepsy, little is known about the molecular mechanisms
      involved in their regulation. Here, we report that reducing agents, including
      endogenous sulfur-containing amino acid l-cysteine, selectively enhance native T
      type currents in reticular thalamic (nRT) neurons and recombinant Ca(V)3.2
      (alpha1H) currents, but not native and recombinant Ca(V)3.1 (alpha1G)- and
      Ca(V)3.3 (alpha1I)-based currents. Consistent with this data, T-type currents of
      nRT neurons from transgenic mice lacking Ca(V)3.2 channel expression were not
      modulated by reducing agents. In contrast, oxidizing agents inhibited all native
      and recombinant T-type currents non-selectively. Thus, our findings directly
      demonstrate that Ca(V)3.2 channels are the main molecular substrate for redox
      regulation of neuronal T-type channels. In addition, because thalamic T-type
      channels generate low-threshold Ca(2+) spikes that directly correlate with burst
      firing in these neurons, differential redox regulation of these channels may have
      an important function in controlling cellular excitability in physiological and
      pathological conditions and fine-tuning of the flow of sensory information into
      the central nervous system.

PMID- 16644798
TI  - Myosin heavy chain isoform composition and stretch activation kinetics in single
      fibres of Xenopus laevis iliofibularis muscle.
AB  - Skeletal muscle is composed of specialized fibre types that enable it to fulfil
      complex and variable functional needs. Muscle fibres of Xenopus laevis, a frog
      formerly classified as a toad, were the first to be typed based on a combination
      of physiological, morphological, histochemical and biochemical characteristics.
      Currently the most widely accepted criterion for muscle fibre typing is the
      myosin heavy chain (MHC) isoform composition because it is assumed that
      variations of this protein are the most important contributors to functional
      diversity. Yet this criterion has not been used for classification of Xenopus
      fibres due to the lack of an effective protocol for MHC isoform analysis. In the
      present study we aimed to resolve and visualize electrophoretically the MHC
      isoforms expressed in the iliofibularis muscle of Xenopus laevis, to define their
      functional identity and to classify the fibres based on their MHC isoform
      composition. Using a SDS-PAGE protocol that proved successful with mammalian
      muscle MHC isoforms, we were able to detect five MHC isoforms in Xenopus
      iliofibularis muscle. The kinetics of stretch-induced force transients (stretch
      activation) produced by a fibre was strongly correlated with its MHC isoform
      content indicating that the five MHC isoforms confer different kinetics
      characteristics. Hybrid fibre types containing two MHC isoforms exhibited stretch
      activation kinetics parameters that were intermediate between those of the
      corresponding pure fibre types. These results clearly show that the MHC isoforms
      expressed in Xenopus muscle are functionally different thereby validating the
      idea that MHC isoform composition is the most reliable criterion for vertebrate
      skeletal muscle fibre type classification. Thus, our results lay the foundation
      for the unequivocal classification of the muscle fibres in the Xenopus
      iliofibularis muscle and for gaining further insights into skeletal muscle fibre
      diversity.

PMID- 16644799
TI  - Graded recruitment and inactivation of single InsP3 receptor Ca2+-release
      channels: implications for quantal [corrected] Ca2+release.
AB  - Modulation of cytoplasmic free Ca2+ concentration ([Ca2+]i) by receptor-mediated
      generation of inositol 1,4,5-trisphosphate (InsP3) and activation of its receptor
      (InsP3R), a Ca2+-release channel in the endoplasmic reticulum, is a ubiquitous
      signalling mechanism. A fundamental aspect of InsP3-mediated signalling is the
      graded release of Ca2+ in response to incremental levels of stimuli. Ca2+ release
      has a transient fast phase, whose rate is proportional to [InsP3], followed by a
      much slower one even in constant [InsP3]. Many schemes have been proposed to
      account for quantal Ca2+ release, including the presence of heterogeneous
      channels and Ca2+ stores with various mechanisms of release termination. Here, we
      demonstrate that mechanisms intrinsic to the single InsP3R channel can account
      for quantal Ca2+ release. Patch-clamp electrophysiology of isolated insect Sf9
      cell nuclei revealed a consistent and high probability of detecting functional
      endogenous InsP3R channels, enabling InsP3-induced channel inactivation to be
      identified as an inevitable consequence of activation, and allowing the average
      number of activated channels in the membrane patch (N(A)) to be accurately
      quantified. InsP3-activated channels invariably inactivated, with average
      duration of channel activity reduced by high [Ca2+]i and suboptimal [InsP3].
      Unexpectedly, N(A) was found to be a graded function of both [Ca2+]i and [InsP3].
      A qualitative model involving Ca2+-induced InsP3R sequestration and inactivation
      can account for these observations. These results suggest that apparent
      heterogeneous ligand sensitivity can be generated in a homogeneous population of
      InsP3R channels, providing a mechanism for graded Ca2+ release that is intrinsic
      to the InsP3R Ca2+ release channel itself.

PMID- 16644800
TI  - AMP-activated protein kinase--development of the energy sensor concept.
AB  - The LKB1-->AMPK cascade is switched on by metabolic stresses that either inhibit
      ATP production (e.g. hypoxia, hypoglycaemia) or that accelerate ATP consumption
      (e.g. muscle contraction). Any decline in cellular energy status is accompanied
      by a rise in the cellular AMP: ATP ratio, and this activates AMPK by a complex
      and sensitive mechanism involving antagonistic binding of the nucleotides to two
      sites on the regulatory gamma subunits of AMPK. Once activated by metabolic
      stress, AMPK activates catabolic pathways that generate ATP, while inhibiting
      cell growth and biosynthesis and other processes that consume ATP. While the AMPK
      system probably evolved in single-celled eukaryotes to maintain energy balance at
      the cellular level, in multicellular organisms its role has become adapted so
      that it is also involved in maintaining whole body energy balance. Thus, it is
      regulated by hormones and cytokines, especially the adipokines leptin and
      adiponectin, increasing whole body energy expenditure while regulating food
      intake. Some hormones may activate AMPK by an LKB1-independent mechanism
      involving Ca2+/calmodulin dependent protein kinase kinases. Low levels of
      activation of AMPK are likely to play a role in the current global rise in
      obesity and Type 2 diabetes, and AMPK is the target for the widely used
      antidiabetic drug metformin.

PMID- 16644801
TI  - Activation of the cGMP/PKG pathway inhibits electrical activity in rabbit
      urethral interstitial cells of Cajal by reducing the spatial spread of Ca2+
      waves.
AB  - In the present study we used a combination of patch clamping and fast confocal
      Ca2+ imaging to examine the effects of activators of the nitric oxide (NO)/cGMP
      pathway on pacemaker activity in freshly dispersed ICC from the rabbit urethra,
      using the amphotericin B perforated patch configuration of the patch-clamp
      technique. The nitric oxide donor, DEA-NO, the soluble guanylyl cyclase activator
      YC-1 and the membrane-permeant analogue of cGMP, 8-Br-cGMP inhibited spontaneous
      transient depolarizations (STDs) and spontaneous transient inward currents
      (STICs) recorded under current-clamp and voltage-clamp conditions, respectively.
      Caffeine-evoked Cl- currents were unaltered in the presence of SP-8-Br-PET-cGMPs,
      suggesting that activation of the cGMP/PKG pathway does not block Cl- channels
      directly or interfere with Ca2+ release via ryanodine receptors (RyR). However,
      noradrenaline-evoked Cl- currents were attenuated by SP-8-Br-PET-cGMPs,
      suggesting that activation of cGMP-dependent protein kinase (PKG) may modulate
      release of Ca2+ via IP3 receptors (IP3R). When urethral interstitial cells (ICC)
      were loaded with Fluo4-AM (2 microm), and viewed with a confocal microscope, they
      fired regular propagating Ca2+ waves, which originated in one or more regions of
      the cell. Application of DEA-NO or other activators of the cGMP/PKG pathway did
      not significantly affect the oscillation frequency of these cells, but did
      significantly reduce their spatial spread. These effects were mimicked by the
      IP3R blocker, 2-APB (100 microm). These data suggest that NO donors and
      activators of the cGMP pathway inhibit electrical activity of urethral ICC by
      reducing the spatial spread of Ca2+ waves, rather than decreasing wave frequency.

PMID- 16644802
TI  - Activation of AMP-activated protein kinase in the liver: a new strategy for the
      management of metabolic hepatic disorders.
AB  - It is now becoming evident that the liver has an important role in the control of
      whole body metabolism of energy nutrients. In this review, we focus on recent
      findings showing that AMP-activated protein kinase (AMPK) plays a major role in
      the control of hepatic metabolism. AMPK integrates nutritional and hormonal
      signals to promote energy balance by switching on catabolic pathways and
      switching off ATP-consuming pathways, both by short-term effects on
      phosphorylation of regulatory proteins and by long-term effects on gene
      expression. Activation of AMPK in the liver leads to the stimulation of fatty
      acid oxidation and inhibition of lipogenesis, glucose production and protein
      synthesis. Medical interest in the AMPK system has recently increased with the
      demonstration that AMPK could mediate some of the effects of the fat cell-derived
      adiponectin and the antidiabetic drugs metformin and thiazolidinediones. These
      findings reinforce the idea that pharmacological activation of AMPK may provide,
      through signalling and metabolic and gene expression effects, a new strategy for
      the management of metabolic hepatic disorders linked to type 2 diabetes and
      obesity.

PMID- 16644803
TI  - Influence of ageing and physical activity on vascular morphology in rat skeletal
      muscle.
AB  - Key structural and functional properties of the skeletal muscle vasculature that
      underlie diminished vascular conductance with ageing remain obscure. The purpose
      of this investigation was to test the hypotheses that (1) reduced levels of
      spontaneous physical activity in old rats are associated with skeletal muscle
      vascular remodelling (e.g. arterial rarefaction), and (2) consequent to a
      vascular remodelling, calculated shear stress is maintained in feed arteries of
      aged muscle at levels commensurate with that in young. Activity during daily
      light and dark cycles (12-12 h) was measured at 30-s intervals for 2 weeks in
      young (6 months; n = 9) and old (24 months; n = 9) Fisher 344 rats via telemetry.
      Subsequently, the gastrocnemius complex and soleus muscles were excised and all
      feed arteries were counted, isolated, cannulated and maximally dilated for
      measurement of luminal diameter. Resting blood flow was also measured to estimate
      vessel wall shear-stress in the feed arteries perforating the soleus and
      gastrocnemius muscles. Overall, young rats were approximately 1.6 times more
      active during dark periods and approximately 4 times more active during light
      periods than old rats. In addition, young rats had approximately one additional
      feed artery perforating both the soleus (young, 3.3 +/- 0.2; old, 2.6 +/- 0.2
      vessels; P < 0.05) and gastrocnemius (young, 8.8 +/- 0.1; old, 7.5 +/- 0.2
      vessels, P < 0.05) muscles compared with old rats. However, average vessel wall
      shear stress at rest was similar between young and old rats (soleus: Y, 65 +/- 5;
      O, 64 +/- 5 dynes cm(-2); gastrocnemius: Y, 329 +/- 22; O, 327 +/- 27 dynes cm(
      2)) resulting from a larger vessel diameter in arteries from old rats. In
      conclusion, lower activity levels of old rats likely contribute to resistance
      artery rarefaction and, consequently, this provides a plausible mechanism for the
      altered blood flow patterns observed during exercise in aged skeletal muscle.

PMID- 16644804
TI  - Functional consequence of mutation in rat cardiac troponin T is affected
      differently by myosin heavy chain isoforms.
AB  - Cardiac troponin T (cTnT) is an essential component of the thin filament
      regulatory unit (RU) that regulates Ca2+ activation of tension in the heart
      muscle. Because there is coupling between the RU and myosin crossbridges, the
      functional outcome of cardiomyopathy-related mutations in cTnT may be modified by
      the type of myosin heavy chain (MHC) isoform. Ca2+ activation of tension and
      ATPase activity were measured in muscle fibres from normal rat hearts containing
      alpha-MHC isoform and propylthiouracil (PTU)-treated rat hearts containing beta
      MHC isoform. Muscle fibres from normal and PTU-treated rat hearts were
      reconstituted with two different mutations in rat cTnT; the deletion of Glu162
      (cTnT(E162DEL)) and the deletion of Lys211 (cTnT(K211DEL)). Alpha-MHC and beta
      MHC isoforms had contrasting impact on tension-dependent ATP consumption (tension
      cost) in cTnT(E162DEL) and cTnT(K211DEL) reconstituted muscle fibres. Significant
      increases in tension cost in alpha-MHC-containing muscle fibres corresponded to
      17% (P < 0.01) and 23% (P < 0.001) when reconstituted with cTnT(E162DEL) and
      cTnT(K211DEL), respectively. In contrast, tension cost decreased when these two
      cTnT mutants were reconstituted in muscle fibres containing beta-MHC; by
      approximately 24% (P < 0.05) when reconstituted with cTnT(E162DEL) and by
      approximately 17% (P = 0.09) when reconstituted with cTnT(K211DEL). Such
      differences in tension cost were substantiated by the mechano-dynamic analysis of
      cTnT mutant reconstituted muscle fibres from normal and PTU-treated rat hearts.
      Our observation demonstrates that qualitative changes in MHC isoform alters the
      nature of cardiac myofilament dysfunction induced by mutations in cTnT.

PMID- 16644805
TI  - Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid
      oxidation in L6 myotubes.
AB  - We investigated the role of fatty acid availability on AMPK signalling and fatty
      acid oxidation in skeletal muscle. Incubating L6 skeletal muscle myotubes with
      palmitate (a saturated fatty acid) or linoleate (a polyunsaturated fatty acid)
      increased AMPK activity by 56 and 38%, respectively, compared with untreated
      cells. Consistent with these changes, AMPK Thr172 and acetyl-CoA carboxylase beta
      Ser218 phosphorylation were increased in fatty acid treated cells. Pre-incubating
      cells with palmitate or linoleate increased subsequent fatty acid oxidation by 86
      and 92%, respectively. The enhanced AMPK signalling occurred in the absence of
      detectable changes in free AMP and glycogen content. The activity of the upstream
      kinase LKB1 was decreased by fatty acid treatment indicating that AMPK activation
      was not a consequence of LKB1 activation. Instead, fatty acids enhanced LKB1
      phosphorylation of AMPK. Fatty acids did not alter LKB1 activity when either
      synthetic peptide or AMPK alpha(1-312) catalytic fragment was used as substrate
      indicating that the betagamma subunits were required for the fatty acid
      activation. Infection of cells with a dominant-negative AMPK adenovirus reduced
      basal fatty acid oxidation and inhibited the stimulatory effects of fatty acid
      pretreatment on fatty acid oxidation. These results indicate that increasing
      fatty acid availability increases AMPK activity independent of changes in the
      cellular energy charge and support the view that fatty acids may modulate AMPK
      allosterically, making it a better substrate for LKB1.

PMID- 16644808
TI  - How should we rate research?

PMID- 16644806
TI  - The cation-chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat
      hippocampus.
AB  - Earlier studies indicate a crucial role for the interconnected network of
      intrinsically bursting CA3 pyramidal neurons in the generation of in vivo
      hippocampal sharp waves (SPWs) and their proposed neonatal in vitro counterparts,
      the giant depolarizing potentials (GDPs). While mechanisms involving ligand- and
      voltage-gated channels have received lots of attention in the generation of CA3
      network events in the immature hippocampus, the contribution of ion-transport
      mechanisms has not been extensively studied. Here, we show that bumetanide, a
      selective inhibitor of neuronal Cl- uptake mediated by the Na+-K+-2Cl-
      cotransporter isoform 1 (NKCC1), completely and reversibly blocks SPWs in the
      neonate (postnatal days 7-9) rat hippocampus in vivo, an action also seen on GDPs
      in slices (postnatal days 1-8). These findings strengthen the view that GDPs and
      early SPWs are homologous events. Gramicidin-perforated patch recordings
      indicated that NKCC1 accounts for a large ( approximately 10 mV) depolarizing
      driving force for the GABAA current in the immature CA3 pyramids. Consistent with
      a reduction in the depolarization mediated by endogenous GABAA-receptor
      activation, bumetanide inhibited the spontaneous bursts of individual neonatal
      CA3 pyramids, but it slightly increased the interneuronal activity as seen in the
      frequency of spontaneous GABAergic currents. An inhibitory effect of bumetanide
      was seen on the in vitro population events in the absence of synaptic GABAA
      receptor-mediated transmission, provided that a tonic GABAA receptor-mediated
      current was present. Our work indicates that NKCC1 expressed in CA3 pyramidal
      neurons promotes network activity in the developing hippocampus.

PMID- 16644809
TI  - Creative destruction in the NHS.

PMID- 16644810
TI  - Depression should be managed like a chronic disease.

PMID- 16644811
TI  - Cure of cutaneous melanoma.

PMID- 16644813
TI  - Paired kidney transplants to start in the United Kingdom.

PMID- 16644814
TI  - Payment offered to injured trial participants has strings attached.

PMID- 16644815
TI  - The public needs better understanding of drug regulation.

PMID- 16644818
TI  - Generic medicines could rescue EU governments' spending.

PMID- 16644819
TI  - A few health insurers monopolise US market.

PMID- 16644821
TI  - Bush administration promotes health savings accounts.

PMID- 16644822
TI  - France urged to close high risk operating theatres.

PMID- 16644825
TI  - Bird flu adds to Sudans woes as UN warns of risk to aid operations.

PMID- 16644826
TI  - Legalising assisted dying does not affect palliative care, says US expert.

PMID- 16644828
TI  - Diagnosis and treatment of chronic hepatitis C infection.

PMID- 16644829
TI  - The patient's journey: living with diabetes.

PMID- 16644830
TI  - Normal skull suture variant mimicking intentional injury.

PMID- 16644831
TI  - Principles of control of cancer pain.

PMID- 16644833
TI  - Should we screen for depression?

PMID- 16644834
TI  - The case for psychological treatment centres.

PMID- 16644835
TI  - New UK policy on overseas doctors: thank God for the American Dream.

PMID- 16644836
TI  - New UK policy on overseas doctors: has far reaching effects.

PMID- 16644837
TI  - New UK policy on overseas doctors: also affects international medical graduates
      graduating from UK institutions.

PMID- 16644838
TI  - New UK policy on overseas doctors: international medical graduates invest 7500
      pounds sterling in getting first job.

PMID- 16644839
TI  - New UK policy on overseas doctors: what future for international medical
      graduates in the NHS?

PMID- 16644840
TI  - Role of MRI in diagnosing multiple sclerosis: early diagnosis using MRI and early
      treatment delays disease conversion.

PMID- 16644841
TI  - Role of MRI in diagnosing multiple sclerosis: magnetic resonance imaging is
      valuable.

PMID- 16644843
TI  - Mobile phone use and risk of glioma in adults: conclusions are questionable.

PMID- 16644844
TI  - Mobile phone use and risk of glioma in adults: study has many flaws.

PMID- 16644845
TI  - Mobile phone use and risk of glioma in adults: results are difficult to interpret
      because of limitations.

PMID- 16644846
TI  - Textbook of Pharmaceutical Medicine warns of trial risks.

PMID- 16644847
TI  - Clinical research in primary care needs urgent boost.

PMID- 16644848
TI  - Predictive value of metabolic syndrome is not clear.

PMID- 16644849
TI  - Fetuses can feel pain.

PMID- 16644850
TI  - Herbst/multibracket appliance treatment of Class II division 1 malocclusions in
      early and late adulthood. a prospective cephalometric study of consecutively
      treated subjects.
AB  - A prospective study of 23 consecutive adult Class II division 1 malocclusion
      subjects (19 female and 4 male) treated with the Herbst/multibracket (MB)
      appliance is presented. The skeletal, dental, and facial profile changes were
      evaluated in addition to the mechanism of Class II correction during the Herbst
      phase and the settling of the occlusion during the MB phase. The mean pre
      treatment age of the subjects was 21.9 years (15.7-44.4 years). Lateral head
      films in habitual occlusion from before treatment (T1) and after the Herbst (T2)
      and MB (T3) phases were analysed using standard cephalometrics and the sagittal
      occlusion analysis. For the standard cephalometrics, normal growth standards were
      utilized as control parameters. All patients were treated successfully to a Class
      I occlusal relationship with a normal overjet and overbite. The mandibular
      variables (SNB and SNPg) showed an angular increase (1.22 and 0.93 degrees,
      respectively) during T2-T1 followed by an angular reduction (0.40 and 0.23
      degrees, respectively) during T3-T2. Compared with normal growth standards, all
      mandibular parameters were affected favourably by Herbst/MB treatment. Both the
      skeletal and soft tissue profile convexities were significantly reduced. Over the
      entire observation period (T3-T1), the largest amount of profile convexity
      reduction was seen for the soft tissue profile excluding the nose (mean 3.14
      degrees). Class II correction was achieved by both skeletal and dental changes:
      overjet correction by 13 per cent skeletal and 87 per cent dental changes, and
      molar correction by 22 per cent skeletal and 78 per cent dental changes. In
      conclusion, on a short-term basis, the Herbst/MB appliance combination was found
      to be a powerful tool for non-surgical, non-extraction, treatment of Class II
      division I subjects in early and late adulthood.

PMID- 16644851
TI  - Foetal alcohol syndrome: a dental and skeletal age analysis of patients and
      controls.
AB  - Foetal alcohol syndrome (FAS) consists of multisystem abnormalities and is caused
      by the excessive intake of alcohol during pregnancy. The teratogenic effect of
      alcohol on the human foetus has now been established beyond reasonable doubt and
      FAS is one of the most important human teratogenic conditions known today. The
      purpose of this study was to assess the dental age (DA) and skeletal age (SA) of
      children with FAS and compare them with matched controls. The samples of 90
      children diagnosed with FAS and 90 controls were matched for age, gender, and
      social class. The mean chronological age (CA) of the FAS subjects was 8.95 years,
      with the controls slightly older at 9.04 years. This difference was not
      significant. Dental maturity was determined by assessing the stage of tooth
      formation and SA assessment was made from hand-wrist radiographs for the patients
      and controls by assigning a SA and comparing it with standard plates. The means
      and standard deviations of CA and DA for the stages of calcification were
      calculated and the Pearson ranked order correlation coefficient was applied to
      measure the associations between skeletal maturity indicators and DA. t-tests
      were used to test for group differences between independent groups, and paired t
      tests to determine paired group differences. This study provided evidence of a
      positive association between DA and SA in both the FAS children and the controls.
      The data suggest that both DA and SA may be a reflection of general somatic
      growth. It must be acknowledged that growth of individuals is often irregular,
      when any norms of development based on central tendencies and variabilities of
      healthy children are applied. Some aspects of growth and development for healthy
      children may show a variable pattern of growth. Therefore, correlation of these
      aspects of growth and development will often not show the degree of correlation
      that theoretically exists between different areas of growth and development. A
      more complete appraisal of the entire skeleton and an evaluation of the entire
      dentition, rather than just the mandibular teeth, might improve the correlation
      between the variables.

PMID- 16644852
TI  - Evaluation of the centroid method of occlusion for studying mandibular and
      maxillary growth.
AB  - The aim of this study was to evaluate the centroid method of occlusion for
      studying mandibular growth and development. This novel technique comparatively
      expresses the direction of growth of the maxilla and mandible as a single unit.
      The centroid 'G' was geometrically calculated from the triangle Deltaabc, which
      comprised the palatal, articulare-gnathion (Ar-Gn), and A-B planes. The plane
      angles and positional relationship of the centroid with the upper first molar was
      investigated, focusing on differences between genders and malocclusions. Lateral
      cephalograms were obtained of 26 males and 51 females with a 'normal' Class I
      occlusion, 216 females with a Class III incisor relationship, and 230 females,
      all aged >18 years, with a Class II incisor relationship. Bolton standards and
      Sakamoto's data were used to determine changes in the angle of the palatal plane
      to the Ar-Gn plane. Non-significant levels of variation were observed in the
      angle of the palatal plane to the Ar-Gn plane during the developmental period
      from childhood to adulthood. Among Class I adult subjects, Deltaabc was similar
      between genders and the centroid G was located near the occlusal surface of the
      upper first molar. There was no difference in the area of Deltaabc between
      malocclusion types. The positional relationship of the centroid G with the upper
      first molar revealed a shift of the centroid mesially and cervically during the
      transition from Class III to Class I to Class II. These findings indicate that
      the centroid method can contribute to orthopaedic diagnosis and the planning of
      treatment strategies.

PMID- 16644853
TI  - Rhythm control strategies for "symptomatic" persistent atrial fibrillation: is
      achieving sinus rhythm enough?
AB  - A significant proportion of symptomatic patients who undergo DC cardioversion for
      persistent atrial fibrillation are unable to correctly perceive their rhythm
      shortly afterwards. Restoration of sinus rhythm does not necessarily result in
      improvement in symptoms.

PMID- 16644854
TI  - Wide spectrum of presentation and variable outcomes of isolated left ventricular
      non-compaction.
AB  - OBJECTIVES: To investigate diagnostic routes, echocardiographic substrates,
      outcomes and prognostic factors in patients with isolated ventricular non
      compaction (IVNC) identified by echocardiographic laboratories with referral from
      specialists and primary care physicians. PATIENTS AND DESIGN: Since 1991, all
      patients with suspected IVNC were flagged and followed up on dedicated databases.
      Patients were divided into symptom-based and non-symptom-based diagnostic
      subgroups. RESULTS: 65 eligible patients were followed up for 6-193 months (mean
      46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of
      left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%)
      LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom
      based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was
      characterised by younger age, lower prevalence of ECG abnormalities, better
      systolic function and lower left atrial size, whereas the extent of non
      compaction was not different. No major cardiovascular events occurred in the non
      symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients
      experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan-Meier
      analysis). Independent predictors of cardiovascular death or heart
      transplantation were New York Heart Association class III-IV, sustained
      ventricular arrhythmias and left atrial size. CONCLUSIONS: IVNC is associated
      with a broad spectrum of clinical and pathophysiological findings, and the
      overall natural history and prognosis may be better than previously thought.
      Adult patients with incidental or familial discovery of IVNC have an encouraging
      outlook, whereas those who have symptoms of heart failure, a history of sustained
      ventricular tachycardia or an enlarged left atrium have an unstable course and
      more severe prognosis.

PMID- 16644855
TI  - Rapid screening for major depression in post-myocardial infarction patients: an
      investigation using Beck Depression Inventory II items.
AB  - OBJECTIVE: To determine the ability of three questions from the Beck Depression
      Inventory II (BDI-II) to detect major depressive disorder (MDD) in a cohort of
      patients hospitalised for acute myocardial infarction (MI). DESIGN: Prospective
      observational study. SETTING: Coronary care unit and cardiac step-down unit of an
      urban academic medical centre. PATIENTS: 131 post-MI patients within 72 h of
      symptom onset. INTERVENTIONS: Patients were administered the BDI-II and
      participated in a structured diagnostic interview for MDD. Three individual BDI
      II items (regarding sadness, loss of interest and loss of pleasure) were examined
      individually and in two-question combinations to determine their ability to
      screen for MDD. MAIN OUTCOME MEASURES: Sensitivity, specificity, negative and
      positive predictive values and proportion of patients with MDD correctly
      identified. RESULTS: The individual items and two-question combinations had good
      sensitivity (76-94%), specificity (70-88%) and negative predictive values (97
      99%). Item 1 (sadness) performed the best of the individual items (48% with a
      positive response to the item had MDD; 3% with a negative response had MDD; over
      80% of patients with MDD were correctly identified). A combination of questions
      about sadness and loss of interest performed best among the two-question
      combinations (37% with positive response had MDD v 1% with a negative response;
      94% of patients with MDD were identified). CONCLUSIONS: One to two questions
      regarding sadness and loss of interest serve as simple and effective screening
      tools for post-MI depression.

PMID- 16644856
TI  - Long-term impact of multivessel disease on cause-specific mortality after ST
      elevation myocardial infarction treated with reperfusion therapy.
AB  - OBJECTIVES: To investigate the long-term impact of multivessel coronary artery
      disease (MVD) on cause-specific mortality in patients with ST elevation
      myocardial infarction (STEMI) treated with reperfusion therapy. METHODS AND
      RESULTS: Patients with STEMI (n = 395) treated with primary angioplasty or
      thrombolysis in the setting of a randomised clinical trial were enrolled in the
      study. Follow up was 8 (2) years. For patients who died all available records
      were reviewed to assess the specific cause of death. MVD was present in 57% of
      patients. Patients with MVD were older and more of them had diabetes and previous
      myocardial infarction. Compared with the non-MVD group, residual left ventricular
      ejection fraction was lower (45.9% v 49.6%, p = 0.001) and total mortality was
      higher in patients with MVD (32% v 19%, p = 0.002). After adjustment for
      potential confounders this association was not significant (hazard ratio 1.4, 95%
      confidence interval (CI) 0.9 to 2.2). When the specific cause of death was
      considered, sudden death was comparable between patients with and without MVD
      (10% v 8%, p = 0.49) but death caused by heart failure was significantly higher
      in patients with MVD (hazard ratio 7.4, 95% CI 1.7 to 32.2). CONCLUSION: Patients
      with STEMI and MVD have a higher long-term mortality than do patients with non
      MVD. MVD is not an independent predictor of long-term total mortality or sudden
      death. However, MVD is a very strong and independent predictor of long-term death
      caused by heart failure.

PMID- 16644857
TI  - Stenting of hypoplastic aortic segments with mild pressure gradients and arterial
      hypertension.
AB  - OBJECTIVE: To determine the safety, feasibility and effectiveness of stent
      expansion of hypoplastic aortic segments with pressure gradients in patients with
      arterial hypertension. DESIGN: Non-randomised prospective clinical trial.
      SETTING: Tertiary referral centre, congenital cardiac unit. PATIENT SELECTION: 20
      consecutive patients (median age 14.5 years, range 11.6-38.8 years) with arterial
      hypertension and a hypoplastic segment of the aorta. Seventeen patients had
      successful previous arch interventions in a coarctation site. INTERVENTIONS:
      Stent deployment in hypoplastic arch segments. MAIN OUTCOME MEASURES: Gradient
      across the aortic arch; complications early and during follow up; residual
      hypertension. RESULTS: 23 stents were deployed: 13 in the cross and 10 in the
      isthmus. The mean gradient across the aortic arch decreased from 16 (SD 6)
      (median 17) to 3 (4) (median 1) mm Hg (p < 0.001). In a few patients a mild
      gradient persisted just distal to the left carotid artery due to residual
      orificial narrowing or acute angulation. No complications occurred during or
      after the procedure. During follow up of 2.2 years (range 0.2-4.8 years) arterial
      hypertension resolved in 10 patients and 10 required residual drug treatment with
      better control of blood pressures. CONCLUSIONS: Pressure loss due to residual
      hypoplastic aortic segments can be treated effectively and safely with stent
      expansion. Some patients remain mildly hypertensive and require additional drug
      treatment.

PMID- 16644858
TI  - Infective endocarditis in a Finnish teaching hospital: a study on 326 episodes
      treated during 1980-2004.
AB  - OBJECTIVES: To evaluate potential changes of infective endocarditis (IE) in
      patients treated in a Finnish teaching hospital during the past 25 years.
      PATIENTS: 326 episodes of IE in 303 patients treated during 1980-2004 were
      evaluated for clinical characteristics and their changes over time. RESULTS: The
      mean age of the patients increased with time (from 47.2 to 54.5 years, p =
      0.003). Twenty-five (7.7%) episodes were associated with intravenous drug use
      (IVDU), with a significant increase of these episodes after 1996 (from 0 to 19
      (20%), p < 0.001). Viridans streptococci were the most common causative agents of
      IE during 1980-1994, but after that Staphylococcus aureus was the most common
      pathogen (p = 0.015). The proportion of IE of the aortic valve decreased during
      the study (from 30 (49%) to 26 (27%), whereas the proportions of mitral (11 (18%)
      to 33 (35%) and tricuspid valve IE (0 to 13 (14%) increased correspondingly (p =
      0.001). This was mainly due to more patients with IVDU. Chronic dialysis for
      renal failure as an underlying condition increased over time (from 0 to 7 (7.4%),
      p = 0.015) but no other predisposing conditions changed. Complications such as
      neurological manifestations and heart failure did not change in frequency, but
      the incidence of lung emboli increased (from 0% to 10.5%, p < 0.001); 83% of
      these emboli occurred in patients with IVDU. The proportion of patients requiring
      surgical treatment and mortality due to IE did not change. CONCLUSIONS: During
      these 25 years, the causative agents, affected valves and complications of IE
      changed to some degree. These changes were mainly attributed to the increase of
      IVDU-associated IE. Except for the increase in age, the clinical presentation and
      outcome in non-addicts remained substantially unchanged.

PMID- 16644859
TI  - Exercise does not cause an arm-leg blood pressure gradient in healthy children.

PMID- 16644860
TI  - Magnitude and consequences of undertreatment of high-risk patients with non-ST
      segment elevation acute coronary syndromes: insights from the DESCARTES Registry.
AB  - OBJECTIVE: To analyse intensity of treatment of high-risk patients with non-ST
      elevation acute coronary syndromes (NSTEACS) included in the DESCARTES
      (Descripcion del Estado de los Sindromes Coronarios Agudos en un Registro
      Temporal Espanol) registry. PATIENTS AND SETTING: Patients with NSTEACS (n =
      1877) admitted to 45 randomly selected Spanish hospitals in April and May 2002
      were studied. DESIGN: Patients with ST segment depression and troponin rise were
      considered high risk (n = 478) and were compared with non-high risk patients (n =
      1399). RESULTS: 46.9% of high-risk patients versus 39.5% of non-high-risk
      patients underwent angiography (p = 0.005), 23.2% versus 18.8% (p = 0.038)
      underwent percutaneous revascularisation, and 24.9% versus 7.4% (p < 0.001) were
      given glycoprotein IIb/IIIa inhibitor. In-hospital and six-month mortality were
      7.5% versus 1.1% and 17% versus 4.6% (p < 0.001), respectively. A treatment score
      (> or = 4, 2-3 and < 2) was defined according to the number of class I
      interventions recommended in clinical guidelines: aspirin, clopidogrel, beta
      blockers, angiotensin-converting enzyme inhibitors, statins and
      revascularisation. Independent predictors of six-month mortality were age (odds
      ratio (OR) 1.07, 95% confidence interval (CI) 1.04 to 1.10, p < 0.001), diabetes
      (OR 1.92, 95% CI 1.14 to 3.22, p = 0.014), previous cardiovascular disease (OR
      4.17, 95% CI 1.63 to 10.68, p = 0.003), high risk (OR 2.20, 95% CI 1.30 to 3.71,
      p = 0.003) and treatment score < 2 versus > or = 4 (OR 2.87, 95% CI 1.27 to 6.52,
      p = 0.012). CONCLUSIONS: Class I recommended treatments were underused in high
      risk patients in the DESCARTES registry. This undertreatment was an independent
      predictor of death of patients with an acute coronary syndrome.

PMID- 16644861
TI  - Reverse remodelling in heart failure with cardiac resynchronisation therapy.
AB  - This review examines the use of cardiac resynchronisation therapy (CRT) for
      chronic, severe, systolic heart failure. Left ventricular (LV) remodelling is the
      final common pathway of systolic heart failure and portends a poor prognosis. It
      is characterised by progressive LV dilatation, deterioration of ventricular
      contractile function and distortion of LV cavity shape. The LV remodelling
      process is triggered by prolonged pressure or volume overload, loss of
      contracting myocytes from myocardial infarction, genetic abnormalities of
      contractile proteins or exposure to cardiotoxic agents. Current therapeutic
      strategies for systolic heart failure aim to slow or halt the remodelling
      process. "Reverse remodelling" is a relatively new concept, where progressive LV
      dilatation and deterioration in contractile function are not simply arrested, but
      partially reversed. Cardiac resynchronisation therapy is a novel and effective
      treatment for systolic heart failure, and is associated with reverse remodelling
      of the LV.

PMID- 16644862
TI  - Atm-deficient mice: an osteoporosis model with defective osteoblast
      differentiation and increased osteoclastogenesis.
AB  - Atm is a Ser/Thr kinase involved in DNA damage response and is required for
      genome integrity and stem cell renewal. Here, we report an additional role for
      Atm in bone remodeling. Atm-/- mice showed reduced bone mass, especially at the
      trabecular bones, accompanied by a decrease in bone formation rate and defective
      differentiation of osteoblasts, but normal numbers of osteoprogenitor cells and
      osteoblasts. Atm might affect osteoblast differentiation by modulating the
      expression of osterix, a lineage-specific transcription factor essential for
      osteoblast maturation, likely via the bone morphogenetic proteins pathway. Atm-/-
      mice also displayed a marked increase in osteoclastogenesis and bone resorption,
      although Atm had no cell-autonomous effect on osteoclast differentiation and
      resorption. Increased osteoclastogenesis could be caused by a substantial
      reduction in testosterone and estradiol levels in male and female mice,
      respectively. The steroid hormone deficiency is a result of gonad developmental
      defects, which led to an increase in serum gonadotrophic hormone, FSH via a
      feedback regulation. Overall, these results indicate that Atm deficiency leads to
      osteoporosis mainly as a result of hypogonadism-induced bone resorption together
      with compromised osteoblast differentiation, and that Atm plays a positive role
      in regulating expression of osteoblast-specific transcription factor, osterix.

PMID- 16644863
TI  - Direct detection of null alleles in SNP genotyping data.
AB  - Pinpointing genetic associations in the human genome relies heavily on the
      accuracy of the underlying genotype data. Null alleles can generate significant
      inaccuracies in genotype data and can negatively affect the statistical power of
      a study. Existing quality control (QC) tests, including tests of Hardy-Weinberg
      equilibrium, are not sensitive enough to detect the presence of even moderately
      frequent null alleles in the data. We show that direct analysis of raw data from
      a quantitative genotyping platform can detect up to 75% of null alleles, even at
      frequencies below the sensitivity of more traditional methods. Detecting
      unexpected null alleles not only has benefits in QC of genotype data but may also
      be valuable in detecting rare, functional null alleles that would otherwise be
      missed.

PMID- 16644864
TI  - Neurofibromin is a novel regulator of RAS-induced signals in primary vascular
      smooth muscle cells.
AB  - Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the
      NF1 tumor suppressor gene. Neurofibromin is encoded by NF1 and functions as a
      negative regulator of Ras activity. NF1 patients develop renal artery stenosis
      and arterial occlusions resulting in cerebral and visceral infarcts. Further, NF1
      patients develop vascular neurofibromas where tumor vessels are invested in a
      dense pericyte sheath. Although it is well established that aberrations in Ras
      signaling lead to human malignancies, emerging data generated in genetically
      engineered mouse models now implicate perturbations in the Ras signaling axis in
      vascular smooth muscular cells (VSMCs) as central to the initiation and
      progression of neointimal hyperplasia and arterial stenosis. Despite these
      observations, the function of neurofibromin in regulating VSMC function and how
      Ras signals are terminated in VSMCs is virtually unknown. Utilizing VSMCs
      harvested from Nf1+/- mice and primary human neurofibromin-deficient VSMCs, we
      identify a discrete Ras effector pathway, which is tightly regulated by
      neurofibromin to limit VSMC proliferation and migration. Thus, these studies
      identify neurofibromin as a novel regulator of Ras activity in VSMCs and provide
      a framework for understanding cardiovascular disease in NF1 patients and a
      mechanism by which Ras signals are attenuated for maintaining VSMC homeostasis in
      blood vessel walls.

PMID- 16644865
TI  - Genetic variation in IL6 gene and type 2 diabetes: tagging-SNP haplotype analysis
      in large-scale case-control study and meta-analysis.
AB  - Interleukin-6 (IL-6, gene symbol IL6) is a proinflammatory cytokine. High
      circulating IL-6 levels have been associated with insulin resistance and greater
      risk of type 2 diabetes. Using a linkage disequilibrium (LD)-based approach, we
      sought to investigate the associations of the common polymorphisms
      comprehensively defining the genetic variability at the IL6 locus with diabetes
      risk. We conducted a case-control study of 2691 cases of type 2 diabetes (1692
      women and 999 men) and 3237 control subjects (2238 women and 999 men) from the
      Nurses' Health Study and the Health Professional Follow-up Study. Pairwise LD
      analysis indicated that all the IL6 polymorphisms (rs2069827, rs1800797,
      rs1800795, rs1554606, rs2069849, rs2069861 and rs1818879) were in strong LD. We
      did not find significant associations between IL6 polymorphisms and the risk of
      type 2 diabetes in women or men, individually or in haplotypes. In addition, none
      of the IL6 polymorphisms was significantly associated with the plasma levels of
      IL-6 in the control subjects. Our meta-analysis of 5383 diabetes case and 12 069
      controls indicated a null association between the best-studied 5' promoter
      polymorphism--174G>C (rs1800795)--and diabetes risk. Diversity in adiposity, age
      and sex could not account for the heterogeneity across different studies. In
      summary, the data in this study do not support substantial associations between
      the common polymorphisms in IL6 gene and circulating IL-6 levels and the risk of
      type 2 diabetes.

PMID- 16644866
TI  - The role of PI3K/AKT, MAPK/ERK and NFkappabeta signalling in the maintenance of
      human embryonic stem cell pluripotency and viability highlighted by
      transcriptional profiling and functional analysis.
AB  - Understanding the molecular mechanism by which pluripotency is maintained in
      human embryonic stem cells (hESC) is important for the development of improved
      methods to derive, culture and differentiate these into cells of potential
      therapeutic use. Large-scale transcriptional comparison of the hES-NCL1 line
      derived from a day 8 embryo with H1 line derived from a day 5 embryo (WiCell
      Inc.) showed that only 0.52% of the transcripts analysed varied significantly
      between the two cell lines. This is within the variability range that has been
      reported when hESC derived from days 5-6 embryos have been compared with each
      other. This implies that transcriptional differences between the cell lines are
      likely to reflect their genetic profile rather than the embryonic stage from
      which they were derived. Bioinformatic analysis of expression changes observed
      when these cells were induced to differentiate as embryoid bodies suggested that
      quite a few of the downregulated genes were components of signal transduction
      networks. Subsequent analysis using western blotting, flow cytometry and antibody
      arrays implicated components of the PI3K/AKT kinase, MAPK/ERK and NFkappabeta
      pathways and confirmed that these components are decreased upon differentiation.
      Disruption of these pathways in isolation using specific inhibitors resulted in
      loss of pluripotency and/or loss of viability suggesting the importance of such
      signalling pathways in embryonic stem cell maintenance.

PMID- 16644867
TI  - Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice.
AB  - Prohormone convertase 1 (PC1) mutations lead to obesity in humans. However, Pc1
      knockout mice do not become obese; in fact, they are runted due to a defect in
      growth-hormone releasing hormone processing, leading to the speculation that PC1
      subserves different functions between mouse and human. Here, we report a novel
      allele of mouse Pc1 (N222D) that leads to obesity, abnormal proinsulin processing
      and multiple endocrinological defects. Increased energy intake and a more
      efficient metabolism contribute to the obesity in Pc1(N222D/N222D) mice.
      Defective proinsulin processing leads to glucose intolerance, but neither insulin
      resistance nor diabetes develop despite obesity. The obesity is associated with
      impaired autocatalytic activation of mature PC1 and reduced hypothalamic alpha
      MSH. This is the first characterization of Pc1 mutation in a model organism that
      mimics human PC1 deficiency.

PMID- 16644868
TI  - Pharmacologic and genetic inhibition of hsp90-dependent trafficking reduces
      aggregation and promotes degradation of the expanded glutamine androgen receptor
      without stress protein induction.
AB  - The molecular chaperone hsp90 has emerged as an important therapeutic target in
      cancer and neurodegenerative diseases, including the polyglutamine expansion
      disorders, because of its ability to regulate the activity, turnover and
      trafficking of many proteins. For neurodegenerative disorders associated with
      protein aggregation, the rationale has been that inhibition of hsp90 by
      geldanamycin and related compounds activates heat shock factor 1 (HSF1) to induce
      the production of the chaperones hsp70 and hsp40 that promote disaggregation and
      protein degradation. However, we show here that geldanamycin blocks the
      development of aggregates of the expanded glutamine androgen receptor (AR112Q) of
      Kennedy disease in Hsf1(-/-) mouse embryonic fibroblasts where these chaperones
      are not induced. Geldanamycin is additionally known to inhibit hsp90-dependent
      protein trafficking and to promote proteasomal degradation of client proteins.
      Overexpression of the hsp90 cochaperone p23 also promotes AR112Q degradation, and
      inhibits both AR trafficking and AR112Q aggregation without altering levels of
      hsp70 or hsp40. The hsp90-dependent trafficking mechanism has been defined, and
      it is shown that key immunophilin (IMM) components of the trafficking machinery
      are present in polyglutamine aggregates in cell and mouse models of Kennedy
      disease. Our results indicate that inhibition of the hsp90-dependent trafficking
      mechanism prevents aggregation of the expanded glutamine androgen receptor,
      thereby opening a variety of novel therapeutic approaches to these
      neurodegenerative disorders.

PMID- 16644869
TI  - Origination and evolution of a human-specific transmembrane protein gene, c1orf37
      dup.
AB  - A transmembrane protein gene, c1orf37-dup, was identified as a young gene
      specific to humans. It was derived from the conserved c1orf37 gene through
      retroposition after the divergence of human and chimpanzee. This gene has evolved
      rapidly driven by positive Darwinian selection as evident from a significantly
      high ratio of non-synonymous substitution rate to synonymous substitution rate
      (K(a)/K(s)=2.08) between the new c1orf37-dup and the parental c1orf37 genes.
      Population genetics analysis disclosed a very low level of polymorphism in the
      c1orf37-dup gene and its neighboring regions, thus providing support for the
      occurrence of a recent selective sweep. The GFP experiments revealed that it
      encodes a transmembrane protein associated with cell membranes. Non-random
      distribution of amino acid changes indicates the C1ORF37-DUP protein may have
      evolved diverged functions in the presumably functionally important N-terminal
      region in the cytoplasm and the extracellular loop. These lines of evidence
      support that the functional adaptation of c1orf37-dup has occurred in humans.
      Unlike its ubiquitously expressed parental gene, c1orf37-dup expresses
      selectively in several human tissues including brain. It is suggested that
      c1orf37-dup encodes a novel transmembrane protein in humans which potentially
      endows new properties to cell surface interactions.

PMID- 16644870
TI  - Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and
      neurodegeneration in INCL.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage
      disorder of childhood, is caused by mutations in the palmitoyl-protein
      thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated
      (palmitoylated) proteins and its mutation causes abnormal intracellular
      accumulation of fatty-acylated proteins and peptides leading to INCL
      pathogenesis. Although apoptosis is the suggested cause of neurodegeneration in
      INCL, the molecular mechanism(s) of apoptosis remains unclear. Using the PPT1
      knockout (PPT1-KO) mice that mimic INCL, we previously reported that one
      mechanism of apoptosis involves endoplasmic reticulum (ER) stress-induced caspase
      12 activation. However, the human caspase-12 gene contains several mutations,
      which make it functionally inactive. Thus, it has been suggested that human
      caspase-4 is the counterpart of murine caspase-12. Here we report that in the
      human INCL brain ER stress-induced activation of unfolded protein response (UPR)
      mediates caspase-4 and caspase-3 activation and apoptosis. Moreover, we show that
      the INCL brain contains high level of growth-associated protein-43 (GAP-43),
      which is known to undergo palmitoylation. We also demonstrate that transfection
      of cultured INCL cells with a green fluorescent protein-GAP-43 cDNA construct
      shows abnormal localization of this protein in the ER. Further, INCL cells
      manifest evidence of ER stress and UPR (elevated levels of Grp-78/Bip and
      GADD153), caspase-4 as well as caspase-3 activation and cleavage of poly(ADP)
      ribose polymerase, a compelling sign of apoptosis. Most importantly, we show that
      inhibition of caspase-4 activity protects INCL cells from undergoing apoptosis.
      Our results provide insight into at least one of the molecular mechanisms of
      apoptosis in INCL and may allow the identification of potential targets for
      therapeutic intervention.

PMID- 16644871
TI  - The MALDI-TOF mass spectrometric view of the plasma proteome and peptidome.
AB  - BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) and the related technique, surface-enhanced laser
      desorption/ionization (SELDI)-TOF MS, are being applied widely to analyze serum
      or plasma specimens for potential disease markers. METHODS: Reports on the basic
      principles and applications of MALDI-TOF MS were reviewed and related to
      information on abundance and masses of major plasma proteins. OUTCOMES: MALDI-TOF
      MS is a particle-counting method that responds to molar abundance, and ranking of
      plasma proteins by molar abundance increases the rank of small proteins relative
      to traditional ranking by mass abundance. Detectors for MALDI-TOF MS augment the
      bias for detecting smaller components by yielding stronger signals for an
      equivalent number of small vs large ions. Consequently, MALDI-TOF MS is a
      powerful tool for surveying small proteins and peptides comprising the peptidome
      or fragmentome, opening this new realm for analysis. It is complementary to
      techniques such as electrophoresis and HPLC, which have a bias for detecting
      larger molecules. Virtually all of the potential markers identified by MALDI-TOF
      MS to date represent forms of the most abundant plasma proteins. CONCLUSIONS:
      Analyses of serum or plasma by MALDI-TOF MS provide new information mainly about
      small proteins and peptides with high molar abundance. The spectrum of observed
      proteins and peptides suggests value for applications such as assessment of
      cardiovascular risk, nutritional status, liver injury, kidney failure, and
      systemic immune responses rather than early detection of cancer. Extending
      analysis by MALDI-TOF MS to lower abundance components, such as markers for early
      stage cancers, probably will require more extensive specimen fractionation before
      analysis.

PMID- 16644872
TI  - Serum and urine tissue kallikrein concentrations in male-to-female transsexuals
      treated with antiandrogens and estrogens.
AB  - BACKGROUND: The expression of human tissue kallikrein genes is regulated by
      steroid hormones, but most studies have been conducted with cancer cell lines.
      Our purpose was to examine serum and urinary tissue kallikrein concentration
      changes in male-to-female transsexuals before and after treatment with
      antiandrogens and estrogens. METHODS: Thirty-five male-to-female transsexuals
      receiving cyproterone acetate and estrogens (orally or transdermally) were
      included in this study. Serum and urine samples were collected before initiation
      of therapy and 4 and 12 months post therapy. ELISAs were used to measure multiple
      kallikreins in serum and urine. RESULTS: After antiandrogen and estrogen therapy,
      serum testosterone concentrations decreased dramatically, as did serum and
      urinary concentrations of human glandular kallikrein (hK2) and prostate-specific
      antigen (PSA; hK3). Statistically significant but relatively small changes in
      serum and urinary concentrations of many other kallikreins were also seen.
      Kallikreins in serum and urine were correlated before and after treatment.
      CONCLUSIONS: The concentrations of hK2 and hK3, but not of any other kallikreins,
      decrease dramatically after combined antiandrogen and estrogen treatment in male
      to-female transsexuals. The smaller responses of the other kallikreins presumably
      reflect their expression in multiple tissues.

PMID- 16644873
TI  - Multiplex ligation-dependent probe amplification for rapid detection of
      proteolipid protein 1 gene duplications and deletions in affected males and
      carrier females with Pelizaeus-Merzbacher disease.
AB  - BACKGROUND: Pelizaeus-Merzbacher disease is a rare X-linked neurodegenerative
      disorder caused by sequence variations in the proteolipid protein 1 gene (PLP1).
      PLP1 gene duplications account for approximately 50%-75% of cases and point
      variations for approximately 15%-20% of cases; deletions and insertions occur
      infrequently. We used multiplex ligation-dependent probe amplification (MLPA) to
      detect PLP1 gene alterations, especially gene duplications and deletions.
      METHODS: We performed MLPA on 102 samples from individuals with diverse PLP1 gene
      abnormalities and from controls, including 50 samples previously characterized
      for the PLP1 gene by quantitative PCR but which were anonymized for prior results
      and sex. RESULTS: All males with PLP1 gene duplications (n = 13), 1 male with a
      triplication, 2 males with whole gene deletions, and all controls (n = 72) were
      unambiguously assigned to their correct genotype. Of 4 female carriers tested by
      MLPA and quantitative PCR, 3 were duplication carriers by both methods, and 1 was
      a triplication carrier by MLPA and a duplication carrier by quantitative PCR. For
      1 sample with a partial deletion, MLPA showed exon 3 deleted but PCR showed exons
      3 and 4 deleted. Sequence analysis of 2 samples with reduced dosage for exons 3
      and 5 revealed point variations overlapping the annealing site for the
      corresponding MLPA probe. The precision of MLPA analysis was excellent and
      comparable to or better than quantitative PCR, with CVs of 4.3%-9.8%.
      CONCLUSIONS: MLPA is a rapid and reliable method to determine PLP1 gene copies.
      Samples with partial PLP1 gene dosage alterations require confirmation with a non
      MLPA method.

PMID- 16644874
TI  - Integrated single-label liquid-phase assay of APOE codons 112 and 158 and a
      lipoprotein study in British women.
AB  - BACKGROUND: Apolipoprotein E (APOE) is an important element of lipid metabolism
      and, hence, cardiovascular disorders. APOE has 3 main allelic variants: epsilon3,
      epsilon4, and epsilon2. Of these, epsilon3 is the most common, followed by
      epsilon4 and epsilon2. The associations of these isoforms with cardiovascular
      disorders and Alzheimer disease have been widely studied in different
      populations. Most of the genotyping in these studies has been performed with gel
      based methods, which have important limitations, particularly for large
      epidemiologic studies. We therefore developed an integrated "one-tube" liquid
      phase assay. METHODS: To measure APOE isoforms, we developed an integrated single
      label liquid-phase fluorescence assay containing 2 PCR primers, 2 probes, and 2
      quencher oligonucleotides. We used a 384-well LightTyper, but the assay would be
      generically applicable for use with any fluorescence detector with thermal ramp
      control. We validated this method and applied it in the British Women's Heart and
      Health Study. RESULTS: There were 4 melting peaks, at 41, 56, 61, and 69 degrees
      C, which generated 6 distinctive patterns representing genotypic combinations of
      epsilon3, epsilon4, and epsilon2. The magnitude and direction of the associations
      found with total cholesterol, HDL-cholesterol, triglycerides, and estimated LDL
      cholesterol were consistent with previous reports. CONCLUSION: The one-tube
      LightTyper assay presented here enables accurate, convenient, and economical
      genotyping of APOE and can be used for large epidemiologic studies.

PMID- 16644875
TI  - Best practice in primary care pathology: review 5.
AB  - This fifth best practice review examines three series of common primary care
      questions in laboratory medicine: (1) minor liver function test abnormalities;
      (2) laboratory monitoring of patients receiving lithium; and (3) investigation of
      possible venous thromboembolism. The review is presented in question-answer
      format, referenced for each question series. The recommendations represent a
      precis of guidance found using a standardised literature search of national and
      international guidance notes, consensus statements, health policy documents and
      evidence-based medicine reviews, supplemented by Medline Embase searches to
      identify relevant primary research documents. They are not standards but form a
      guide to be set in the clinical context. Most are consensus-based rather than
      evidence-based. They will be updated periodically to take account of new
      information.

PMID- 16644876
TI  - Three cases of pancreatic serous cystadenoma and endocrine tumour.
AB  - AIMS: To report three cases of serous cystadenoma and endocrine tumour in the
      same pancreas, to review the literature and to evaluate the clinicopathological
      features of the tumours. CASES: Three women (71, 57 and 31 years old) were
      admitted to hospital, two for diseases unrelated to the pancreas and the third
      for increasing obstructive jaundice in von Hippel-Lindau disease. Preoperative
      examination showed two distinct lesions in the first patient and only cystic
      lesions in the other two. RESULTS: Histological examination of the pancreas
      showed one serous oligocystic adenoma associated with a benign, well
      differentiated endocrine tumour, one serous oligocystic adenoma associated with
      an endocrine microadenoma, and a von Hippel-Lindau-related cystic neoplasm with a
      well-differentiated endocrine carcinoma. CONCLUSIONS: Serous cystadenoma
      associated with endocrine tumour shows some clinicopathological differences with
      respect to the two tumours considered separately, and with respect to von Hippel
      Lindau-related cases, although there is no convincing evidence at present to
      justify considering this association as a separate entity.

PMID- 16644878
TI  - Adjusting copper concentrations for caeruloplasmin levels in routine clinical
      practice.
AB  - BACKGROUND: An investigation on copper metabolism usually includes the
      measurement of serum levels of copper and caeruloplasmin. Using these levels,
      some laboratories derive levels of non-caeruloplasmin-bound copper (NCC);
      however, a considerable number of patients may show negative values, which is not
      physiologically possible. AIM: To derive an equation for adjusted copper in a
      manner similar to that widely accepted for adjusted calcium. METHODS: A linear
      regression equation for the relationship between caeruloplasmin and copper was
      used: [copper] (micromol/l) = 0.052x[caeruloplasmin] (mg/l). An equation for
      copper adjusted for caeruloplasmin was derived using this equation and the
      reference interval of 10-25 micromol/l for copper. RESULTS: The derived equation
      was [adjusted copper] (micromol/l) = [total copper]
      (micromol/l)+0.052x[caeruloplasmin] (mg/l)+17.5 (micromol/l). The adjusted copper
      concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 micromol/l,
      respectively, with the population having a gaussian distribution. The
      relationship between NCC and the adjusted copper concentrations is linear and
      independent of caeruloplasmin concentration. CONCLUSION: Calculation of copper
      adjusted for caeruloplasmin uses the same variables as those for NCC.
      Accordingly, the problems that are caused by the lack of specificity of
      caeruloplasmin immunoassays are the same as those identified for NCC. This
      calculation, however, overcomes the negative values that are found in a
      considerable minority of patients with NCC, as well as age and sex differences in
      the caeruloplasmin reference interval. As the concept is already familiar to non
      laboratory healthcare professionals in the form of calcium adjusted for albumin,
      this method is potentially less confusing than that for NCC.

PMID- 16644877
TI  - Gastric histology, serological markers and age as predictors of gastric acid
      secretion in patients infected with Helicobacter pylori.
AB  - BACKGROUND: Acid secretion is intimately associated with most upper
      gastrointestinal diseases. Helicobacter pylori infection is a major environmental
      factor modifying acid secretion. AIM: To study the association between the
      pattern of H pylori gastritis and gastric secretory function in a large number of
      subjects without specific upper gastrointestinal disease. METHODS AND MATERIALS:
      Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing
      normal endoscopy. Activity and severity of gastritis, atrophy and H pylori
      infection were assessed in body and antral biopsies. The correlations of
      histological parameters as well as age, sex, height, weight, smoking, serum
      gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple
      linear regression was used to show the best possible predictors of MAO. RESULTS:
      Negative relationships: Body atrophy and body-combined (active and chronic)
      inflammatory scores showed a potent inverse correlation with MAO (correlation
      coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis
      ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age
      (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at
      both antral and body sites had negative relationships with acid output with CC =
      0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H
      pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of
      0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density:
      combined inflammation of both antrum and body positively correlated with MAO (CC
      = 0.29 and 0.38, respectively). Male sex and patient height also positively
      correlated with acid output. Modelling showed that body combined inflammatory
      score, body atrophy, age and serum pepsinogen I are independent predictors of
      acid output (R(2) = 0.62). CONCLUSION: Combination of body gastritis, body
      atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory
      state in populations infected with H pylori.

PMID- 16644879
TI  - No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in
      carotid artery atherosclerosis.
AB  - BACKGROUND: That infections with certain pathogens, by initiating an inflammatory
      response, may contribute to the development of atherosclerosis is suggested by
      clinical and experimental evidence. AIM: To analyse atherosclerotic plaques of
      the carotid artery, samples of apparently healthy greater saphenous veins and
      circulating leucocytes from the same individual patients for the presence of
      Helicobacter pylori and Mycoplasma pneumoniae. METHODS: Samples from 36 patients
      undergoing carotid endarterectomy for symptomatic carotid artery stenosis were
      analysed by polymerase chain reaction for the presence of DNA specific for H.
      pylori and M. pneumoniae. IgG antibody titres against H. pylori and M pneumoniae
      and plasma levels of soluble E-selectin, soluble intercellular adhesion molecule
      1 and soluble vascular cell adhesion molecule-1 were determined. RESULTS: M.
      pneumoniae-specific DNA was detected in the atherosclerotic plaques of 13 of 36
      (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the
      leucocytes of 27 of 36 (75%) patients. No salient association was observed
      between the presence of M. pneumoniae-specific DNA in leucocytes and
      atherosclerotic plaques or veins. A marked correlation between the presence of M.
      pneumoniae in the respective specimens and the studied inflammatory markers or
      the presence of anti-M. pneumoniae antibodies was not observed. H. pylori
      specific DNA could not be detected in the specimens tested. CONCLUSIONS: The
      absence of H. pylori and the random distribution of M. pneumoniae in tissue
      samples obtained from patients with symptomatic carotid artery stenosis do not
      support a role for these pathogens in the development of atherosclerosis due to a
      direct interaction of the bacteria with the vasculature.

PMID- 16644880
TI  - The relationship between an inflammation-based prognostic score (Glasgow
      Prognostic Score) and changes in serum biochemical variables in patients with
      advanced lung and gastrointestinal cancer.
AB  - BACKGROUND: The Glasgow Prognostic Score (GPS), an inflammation-based prognostic
      score formed from standard thresholds of C reactive protein (CRP) and albumin,
      has prognostic value in patients with advanced cancer. Little is known about the
      general biochemical disturbance associated with the systemic inflammatory
      response in cancer. AIM: To examine the relationship between the GPS and blood
      biochemistry in patients with advanced lung and gastrointestinal cancer. METHODS:
      The GPS (albumin <35 g/l = 1 and CRP >10 mg/l = 1 combined to form a prognostic
      score of 0 (normal) and 1 or 2 (abnormal)) and a variety of biochemical variables
      were examined in patients (n = 50) with advanced lung or gastrointestinal cancer
      and in a healthy control group (n = 13). RESULTS: The GPS was normal in all the
      controls, but abnormal in 78% of the cancer group. Serum levels of sodium,
      chloride, creatine kinase, zinc and vitamin D were lower in the cancer group (all
      p<0.01), whereas levels of calcium, copper (both p<0.05), alkaline phosphatase,
      gamma-glutamyl transferase (both p<0.001) and lactate dehydrogenase (p<0.10) were
      raised. In the patient group, with increasing GPS, there was a median reduction
      in Karnofsky Performance Status (25%), haemoglobin (22%), sodium (3%), zinc (15%)
      and survival (93%, all p<0.05) and a median increase in white cell count (129%),
      alkaline phosphatase (217%), gamma-glutamyl transferase (371%) and lactate
      dehydrogenase (130%, all p<0.05). CRP levels were strongly and similarly
      correlated with alkaline phosphatase and gamma-glutamyl transferase, accounting
      for more than 25% of the variation in their activities. CONCLUSION: Several
      correlations were seen between biochemical variables and increasing GPS. In
      particular, chronic activation of the systemic inflammatory response in cancer
      was associated with increase in gamma-glutamyl transferase and alkaline
      phosphatase activity in patients with advanced lung and gastrointestinal cancer.

PMID- 16644881
TI  - Comparison of gene-expression profiles in parallel bone marrow and peripheral
      blood samples in acute myeloid leukaemia by real-time polymerase chain reaction.
AB  - BACKGROUND: Gene signatures (Indicator genes) in bone marrow that provide more
      precise prognostication in haematological malignancy have been identified by
      microarray expression studies. It would be beneficial to measure these diagnostic
      signatures in peripheral blood. AIMS: To determine the degree of correspondence
      of gene expression for a set of Indicator genes between bone marrow and
      peripheral blood in acute myeloid leukaemia (AML). METHODS: Parallel bone marrow
      aspirate and peripheral blood samples were obtained from 19 patients diagnosed
      with AML and mononuclear cells isolated from both sample types. mRNA was globally
      amplified by polyadenylated real-time polymerase chain reaction (polyA RT-PCR);
      the expression of 15 AML Indicator genes, identified from previous microarray
      studies, was measured by RT-PCR. All values were normalised to the mean
      expression of three housekeeping genes (IF2-beta, GAP and RbS9) and were
      statistically compared using SPSS software. RESULTS: No significant difference in
      expression between bone marrow and peripheral blood was observed for 10 of the
      genes (leptin receptor, CD33, adipsin, proteoglycan 1, MB-1, cyclin D3, hSNF2b,
      proteasome iota, HkrT-1 and E2A), indicating its possible use in monitoring
      disease activity in peripheral blood samples, whereas c-myb, HOXA9, LYN, cystatin
      c and LTC4s showed significantly different expression between bone marrow and
      peripheral blood samples. CONCLUSION: These results indicate a possible use for
      the method in monitoring AML in peripheral blood by RT-PCR measurement of
      Indicator genes. In addition, the initial use of polyA PCR facilitates
      translation to very small clinical samples, including fractionated cell
      populations, of particular importance for monitoring haematological malignancy.

PMID- 16644883
TI  - Why I became a haematopathologist.

PMID- 16644882
TI  - Molecular biology of squamous cell carcinoma of the head and neck.
AB  - Squamous cell carcinoma of the head and neck (HNSCC) is a heterogeneous but
      largely preventable disease with complex molecular abnormalities. It arises from
      a premalignant progenitor followed by outgrowth of clonal populations associated
      with cumulative genetic alterations and phenotypic progression to invasive
      malignancy. These genetic alterations result in inactivation of multiple tumour
      suppressor genes and activation of proto-oncogenes, including p16(ink4A), p53,
      cyclin D1, p14(ARF), FHIT, RASSF1A, epidermal growth factor receptor (EGFR), and
      Rb. Intramucosal migration and clonal expansion of transformed cells with
      formation of abnormal genetic fields appear to be responsible for local
      recurrences and development of second primary tumours.

PMID- 16644884
TI  - An audit of the indications for the reporting of blood films: results from the
      National Pathology Benchmarking Study.
AB  - BACKGROUND: The National Pathology Benchmarking Review has completed seven years
      of analysis of the workload of haematology laboratories in the United Kingdom.
      OBJECTIVE: To audit criteria that laboratories use for preparing blood films
      against guidelines published by the International Consensus Group for Haematology
      Review. METHODS: Each laboratory completed a standard questionnaire about the
      number of blood counts and blood films done each year. Information was collected
      on the criteria that were used for preparing a blood film and the manufacturer of
      the equipment used to carry out the full blood count. RESULTS: 46 NHS trusts (93
      laboratory sites) participated in the study. There was wide variation in the
      criteria used for preparing blood films when compared with the consensus
      guidelines. The variation in practice appeared to be irrespective of the type of
      hospital or the manufacturer of the equipment used for the blood count.
      CONCLUSIONS: There is a wide range in laboratory practice in preparing blood
      films. The publication of the consensus guidelines should help to standardise
      practice in this area. The next step in the study is to determine what the film
      review rate should be if these guidelines are implemented. This will then provide
      a benchmark of good practice which laboratories can use to assess their
      performance.

PMID- 16644885
TI  - Targeted screening for genetic haemochromatosis: a combined phenotype/genotype
      approach.
AB  - OBJECTIVE: To evaluate the clinical utility of a targeted screening approach for
      the detection of genetic haemochromatosis. METHODS: Screening by measuring
      fasting serum transferrin saturation (TS) and gene testing was carried out in
      patients in whom a raised serum alanine amino transferase (ALT) activity and
      raised random serum TS had been found on routine blood testing. RESULTS: During
      the 29 month study period, 32 patients homozygous for the C282Y genotype were
      detected from a catchment population of 330,000 by screening blood samples
      referred initially for routine laboratory liver function tests. By comparison,
      during the same period of time and within the same population, only seven
      patients were found by clinical suspicion alone. The patients in the study, after
      treatment by venesection, have shown both clinical and biochemical improvement.
      CONCLUSIONS: The study shows that from a population of patients in whom a routine
      liver function profile had been requested, it is possible to detect subjects
      homozygous for the C282Y HFE genotype who have clinical or biochemical markers of
      iron overload.

PMID- 16644886
TI  - Solid mesenchymal hamartoma in an adult: a case report.
AB  - Mesenchymal hamartoma of the liver (MHL) is an uncommon tumour composed of
      architecturally abnormal bile ducts in an uncommitted myxoid stroma. Most MHL are
      diagnosed in childhood and few cases have been reported in adults. This report
      describes a case of a well defined solid mass in the right lobe of the liver in a
      51 year old man. Preoperative radiological examination revealed a large
      completely solid mass. Biopsy showed a dense fibrous stroma with hyalinisation
      and some bile ducts. A provisional diagnosis of MHL was made. Surgical excision
      was impossible and liver transplantation was undertaken. Definitive pathology
      confirmed the diagnosis. Review of published reports shows this to be the fourth
      case of MHL treated by liver transplantation.

PMID- 16644887
TI  - Adrenal cortical carcinoma metastatic to the breast.
AB  - A 56 year old woman was diagnosed with adrenal cortical carcinoma in May 2003,
      for which she underwent left radical adrenalectomy. Eight months later, in
      January 2004, she presented with a solitary, well delineated, left breast mass
      with central pleomorphic calcifications on mammographic examination. A diagnosis
      of metastatic adrenal cortical carcinoma was made on core biopsy. Subsequently,
      the patient underwent a lumpectomy of the mass, which confirmed the diagnosis. To
      our knowledge, this is the first case report of adrenal cortical carcinoma
      metastatic to the breast.

PMID- 16644888
TI  - An unusual cause of granulomatous inflammation: eosinophilic abscess in
      Langerhans cell histiocytosis.
AB  - Eosinophilic abscess inciting a granulomatous response has rarely been reported
      and appears not to have been described in the setting of a neoplasm. In this
      report, a case is described where a granulomatous response occurred around
      eosinophilic abscesses in a patient with Langerhans cell histiocytosis, an
      association which has not previously been documented. On histology, the excised
      lymph node showed the presence of eosinophilic abscess and necrosis surrounded by
      granulomas, which in turn were surrounded by Langerhans cells, a feature
      confirmed on immunohistochemistry. Although rare, this case highlights the
      importance of careful examination of eosinophilic abscess with granulomatous
      inflammation in order to exclude an underlying neoplasm.

PMID- 16644889
TI  - Haptoglobin polymorphism in a HIV-1 seropositive Brazilian population.
AB  - BACKGROUND: Haptoglobin (Hp) is a plasma protein with antioxidant and
      immunomodulatory properties. Three main genotypes/phenotypes (Hp1-1, Hp2-1, Hp2
      2) show distinctive efficiencies in their activities and have been related to
      susceptibility and outcome in different diseases, including HIV infection.
      OBJECTIVE: To compare Hp genotype distribution between HIV-1 seropositive
      patients and healthy controls. METHODS: 387 Brazilian HIV-1 seropositive
      patients, subclassified as A, B, and C according to the Centers for Disease
      Control, were compared with 142 healthy controls. The influence of the
      polymorphism on iron status (serum iron, ferritin, transferrin, transferrin
      saturation), acute phase proteins (Hp, C reactive protein, fibrinogen, albumin),
      the HIV-1 viral load, and CD4+ T lymphocyte counts was examined. RESULTS: Apart
      from finding lower Hp concentrations among individuals with genotype Hp2-2, no
      other significant difference was observed. CONCLUSIONS: No association was found
      between Hp genotype and either HIV status or indices of HIV progression.

PMID- 16644890
TI  - Histopathology audit of chronic gastritis in India: need for objectivity and
      training.

PMID- 16644891
TI  - Increased troponin I in "wet" beriberi.

PMID- 16644892
TI  - Effective screening of pathology tests controls costs: thrombophilia testing.

PMID- 16644893
TI  - Conditions leading to high CO2 (>5 kPa) in waterlogged-flooded soils and possible
      effects on root growth and metabolism.
AB  - AIMS: Soil waterlogging impedes gas exchange with the atmosphere, resulting in
      low P(O2) and often high P(CO2). Conditions conducive to development of high
      P(CO2) (5-70 kPa) during soil waterlogging and flooding are discussed. The scant
      information on responses of roots to high P(CO2) in terms of growth and
      metabolism is reviewed. SCOPE: P(CO2) at 15-70 kPa has been reported for flooded
      paddy-field soils; however, even 15 kPa P(CO2) may not always be reached, e.g.
      when soil pH is above 7. Increases of P(CO2) in soils following waterlogging will
      develop much more slowly than decreases in P(O2); in soil from rice paddies in
      pots without plants, maxima in P(CO2) were reached after 2-3 weeks. There are no
      reliable data on P(CO2) in roots when in waterlogged or flooded soils. In
      rhizomes and internodes, P(CO2) sometimes reached 10 kPa, inferring even higher
      partial pressures in the roots, as a CO2 diffusion gradient will exist from the
      roots to the rhizomes and shoots. Preliminary modelling predicts that when P(CO2)
      is higher in a soil than in roots, P(CO2) in the roots would remain well below
      the P(CO2) in the soil, particularly when there is ventilation via a well
      developed gas-space continuum from the roots to the atmosphere. The few available
      results on the effects of P(CO2) at > 5 kPa on growth have nearly all involved
      sudden increases to 10-100 kPa P(CO2); consequently, the results cannot be
      extrapolated with certainty to the much more gradual increases of P(CO2) in
      waterlogged soils. Nevertheless, rice in an anaerobic nutrient solution was
      tolerant to 50 kPa CO2 being suddenly imposed. By contrast, P(CO2) at 25 kPa
      retarded germination of some maize genotypes by 50%. With regard to metabolism,
      assuming that the usual pH of the cytoplasm of 7.5 was maintained, every increase
      of 10 kPa CO2 would result in an increase of 75-90 mM HCO3(-) in the cytoplasm.
      pH maintenance would depend on the biochemical and biophysical pH stats (i.e.
      regulatory systems). Furthermore, there are indications that metabolism is
      adversely affected when HCO3(-) in the cytoplasm rises above 50 mM, or even
      lower; succinic dehydrogenase and cytochrome oxidase are inhibited by HCO3(-) as
      low as 10 mM. Such effects could be mitigated by a decrease in the set point for
      the pH of the cytoplasm, thus lowering levels of HCO3(-) at the prevailing P(CO2)
      in the roots. CONCLUSIONS: Measurements are needed on P(CO2) in a range of soil
      types and in roots of diverse species, during waterlogging and flooding. Species
      well adapted to high P(CO2) in the root zone, such as rice and other wetland
      plants, thrive even when P(CO2) is well over 10 kPa; mechanisms of adaptation, or
      acclimatization, by these species need exploration.

PMID- 16644894
TI  - Long term health complaints following the Amsterdam Air Disaster in police
      officers and fire-fighters.
AB  - BACKGROUND: On 4 October 1992, a cargo aircraft crashed into apartment buildings
      in Amsterdam, the Netherlands. Fire-fighters and police officers assisted with
      the rescue work. OBJECTIVES: To examine the long term health complaints in rescue
      workers exposed to a disaster. METHODS: A historical cohort study was performed
      among police officers (n = 834) and fire-fighters (n = 334) who performed at
      least one disaster related task and reference groups of their non-exposed
      colleagues (n = 634 and n = 194, respectively). The main outcome measures
      included digestive, cardiovascular, musculoskeletal, nervous system, airway,
      skin, post-traumatic stress, fatigue, and general mental health complaints;
      haematological and biochemical laboratory values; and urinalysis outcomes.
      RESULTS: Police officers and fire-fighters who were professionally exposed to a
      disaster reported more physical and mental health complaints, compared to the
      reference groups. No clinically relevant statistically significant differences in
      laboratory outcomes were found. CONCLUSIONS: This study is the first to examine
      long term health complaints in a large sample of rescue workers exposed to a
      disaster in comparison to reference groups of non-exposed colleagues. Findings
      show that even in the long term, and in the absence of laboratory abnormalities,
      rescue workers report more health complaints.

PMID- 16644895
TI  - Occupational exposure to organic solvent mixtures during pregnancy and the risk
      of non-syndromic oral clefts.
AB  - OBJECTIVES: To examine the association between maternal occupational exposure to
      mixtures of organic solvents during pregnancy and the risk of non-syndromic oral
      clefts. METHODS: A case-control study (164 cleft lip with/without cleft palate
      (CL/P), 76 cleft palate (CP), 236 controls) was conducted in France to
      investigate the role of maternal occupational exposure to organic solvents at the
      beginning of pregnancy in the risk of non-syndromic oral clefts. An expert
      chemist, guided by a detailed description of the women's occupational tasks,
      assessed exposure for each. Analysis of the findings used logistic regression.
      RESULTS: In the control group, 39% of the women who reported working during
      pregnancy were exposed to at least one type of organic solvent. The risk of oral
      clefts was associated with oxygenated (for CL/P: OR = 1.8, 95% CI 1.1 to 2.9; and
      for CP, OR = 1.4, 95% CI 0.7 to 2.7), chlorinated (OR = 9.4, 95% CI 2.5 to 35.3;
      OR = 3.8, 95% CI 0.7 to 20.7), and petroleum (OR = 3.6, 95% CI 1.5 to 8.8; OR =
      1.2, 95% CI 0.3 to 4.9) solvents. The risk of oral clefts increased linearly with
      level of exposure within the three subgroups of oxygenated solvents we considered
      (aliphatic alcohols, glycol ethers, and other oxygenated solvents, including
      esters, ketones, and aliphatic aldehydes). CONCLUSIONS: Results suggest that
      maternal occupational exposure to organic solvents during pregnancy may play a
      role in the aetiology of oral clefts. The limited number of subjects and the
      problem of multiple exposures require that these results be interpreted
      cautiously.

PMID- 16644896
TI  - Occupational trichloroethylene exposure and non-Hodgkin's lymphoma: a meta
      analysis and review.
AB  - METHODS: Meta-analysis and review of 14 occupational cohort and four case-control
      studies of workers exposed to trichloroethylene (TCE) to investigate the relation
      between TCE exposure and the risk of non-Hodgkin's lymphoma (NHL). Studies were
      selected and categorised based on a priori criteria, and results from random
      effects meta-analyses are presented. RESULTS: The summary relative risk estimates
      (SRRE) for the group of cohort studies that had more detailed information on TCE
      exposure was 1.29 (95% CI 1.00 to 1.66) for the total cohort and 1.59 (95% CI
      1.21 to 2.08) for the seven studies that identified a specific TCE exposed sub
      cohort. SRREs for three studies with cumulative exposure information were 1.8
      (95% CI 0.62 to 5.26) for the lowest exposure category and 1.41 (95% CI 0.61 to
      3.23) for the highest category. Comparison of SRREs by levels of TCE exposure did
      not indicate exposure-response trends. The remaining cohort studies that
      identified TCE exposure but lacked detailed exposure information had an SRRE of
      0.843 (95% CI 0.72 to 0.98). Case-control studies had an SRRE of 1.39 (95% CI
      0.62 to 3.10). Statistically significant findings for the Group 1 studies were
      driven by the results from the subgroup of multiple industry cohort studies
      (conducted in Europe) (SRRE = 1.86; 95% CI 1.27 to 2.71). The SRRE for single
      industry cohort studies was not significantly elevated (SRRE = 1.25; 95% CI 0.87
      to 1.79). CONCLUSIONS: Interpretation of overall findings is hampered by
      variability in results across the Group 1 studies, limited exposure assessments,
      lack of evidence of exposure response trends, lack of supportive information from
      toxicological and mechanistic data, and absence of consistent findings in
      epidemiologic studies of exposure and NHL. Although a modest positive association
      was found in the TCE sub-cohort analysis, a finding attributable to studies that
      included workers from multiple industries, there is insufficient evidence to
      suggest a causal link between TCE exposure and NHL.

PMID- 16644897
TI  - Reducing sick leave by minimal postal intervention: a randomised, controlled
      intervention study.
AB  - BACKGROUND: The lack of efficient medical interventions for combating increasing
      sickness absence rates has lead to the introduction of alternative measures
      initiated by the Norwegian National Insurance Service or at workplaces. AIM: To
      determine whether minimal postal intervention had any effect on the length of
      sick leave. METHODS: Randomised, controlled trial with a one year follow up in
      Northern Norway in 1997 and 1998; 990 consecutive newly sick-listed persons with
      musculoskeletal or mental disorders were studied. Within the intervention group,
      495 eligible sick-listed persons received a general information letter and a
      questionnaire as their sick leave passed 14 days. Possible intervention effects
      were analysed by survival analysis of the probability of returning to work within
      one year, and logistic regressions with benefits at one year as the dependent
      variable. RESULTS: The overall reduction of 8.3 (95% CI -22.5 to 6.0) calendar
      days in mean length of sick leaves in the intervention group compared to
      controls, was not statistically significant. However, intervention significantly
      reduced length of sick leaves in subgroups with mental disorders, and with
      rheumatic disorders and arthritis, and overall for sick leaves lasting 12 weeks
      or more. Young people with low back pain showed an adverse effect to
      intervention. The overall relative risk of receiving benefits due to sickness
      after one year in the intervention group was 0.69 (95% CI 0.51 to 0.93) compared
      to controls. CONCLUSION: The results should encourage employers, insurance
      institutions, and authorities to initiate challenges as questions on the length
      of sick leave and possible modified work measures, during the first few weeks of
      sick leave, for at least some groups of sick-listed persons.

PMID- 16644898
TI  - The prognostic value of depressive symptoms, fear-avoidance, and self-efficacy
      for duration of lost-time benefits in workers with musculoskeletal disorders.
AB  - BACKGROUND: The psychological factors of depressive symptoms, fear-avoidance, and
      self-efficacy are deemed to be important in the work disability process. However,
      the prognostic value of these factors for time on benefit is not well understood.
      AIMS: To analyse the prognostic value of psychological factors for the number of
      days on total compensation benefit over a 12 month period. METHODS: In a
      longitudinal study of 187 workers receiving total compensation benefits due to
      musculoskeletal disorders, the prognostic value of psychological factors measured
      4-5 weeks post-injury for duration on total compensation benefit over 12 months
      was analysed. Cox proportional hazard regression analyses were conducted. Special
      emphasis was given to variable selection and to the analysis of confounding
      effects of potential prognostic variables. RESULTS: The final model indicated
      that increased depressive symptoms and poorer physical health significantly
      increase the number of days on total benefit. Confounders included in the final
      model were pain and fear of income loss. In the final model the impact of fear
      avoidance ceased to be significant when work related variables were included in
      the fully adjusted model. This illustrates that interrelationships between
      variables must be taken into account when building multivariate prognostic
      models. The addition of work related variables to the model did not result in any
      major changes in the adjusted model, which suggests that when measured 4-5 weeks
      post-injury, psychological and physical health factors are strong predictors of
      time on benefits, while work conditions are less important. CONCLUSION: Results
      suggest that the presence of depressive symptoms and poor physical health in
      workers on benefit due to musculoskeletal disorders increases the number of days
      on total compensation benefits significantly, when controlling for confounding
      variables.

PMID- 16644899
TI  - Role of matrix metalloproteinases in intestinal inflammation.
AB  - Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue
      inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several
      structural cells. The balance between MMPs and TIMPs is essential for many
      physiological processes in the gut. However, imbalance between MMPs and TIMPs
      plays an important role in the pathophysiology of diverse intestinal inflammatory
      conditions. We reviewed the role of the MMP/TIMP system in the pathogenesis of
      intestinal inflammatory diseases and pharmacologic perspectives for the use of
      compounds that restore the MMP/TIMP balance.

PMID- 16644900
TI  - Tissue distribution and metabolism of the tyrosine kinase inhibitor ZD6474
      (Zactima) in tumor-bearing nude mice following oral dosing.
AB  - ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]
      quinazolin-4-amine; Zactima] is a tyrosine kinase inhibitor with antiangiogenic
      and antitumor activity currently undergoing human trials for cancer treatment.
      Pharmacokinetic studies in animal models are an important component in the
      clinical development of this agent to relate preclinical studies to patient
      treatment. In the studies presented here, the pharmacokinetics of ZD6474 was
      determined in plasma and tissues of MCF-7 tumor-bearing nude mice following
      single p.o. doses at 10, 25, and 50 mg/kg. Plasma area under the curve and Cmax
      were linear, increasing proportionally with dose. Tissue analysis showed that
      ZD6474 is extensively distributed to tissues, with liver and lung accumulating
      concentrations of 212 microg/g (approximately 450 microM) and 161 microg/g
      (approximately 340 microM), respectively. Tumor levels ranged from 27 to 71
      microg/g at Cmax levels across the three dose ranges, and ZD6474 was distributed
      to all of the tissues in a dose-dependent manner. Analysis of putative ZD6474
      metabolites in feces found four, with the N-demethyl-piperidinyl-ZD6474
      metabolite being the most prominent but still accounting for less than 2% of the
      total amount of ZD6474 present. The lack of significant metabolism of ZD6474 is
      consistent with the relatively long half-life in mice (approximately 30 h), as
      well as that seen in humans (approximately 120 h), and the primary method of drug
      elimination appears to be unchanged in the feces (approximately 25%). The
      incorporation of an empirical approach to dosing in mouse models of cancer in
      preclinical studies may allow for better prediction of clinical efficacy for
      ZD6474 alone and in combination with other therapeutic modalities based on
      equivalent drug exposure.

PMID- 16644901
TI  - Neuroproteomics of the synapse and drug addiction.
AB  - Proteomic analyses of brain tissues are becoming an integral component of
      neuroscientific research. In particular, the essential role of the synapse in
      neurotransmission and plasticity has brought about extensive efforts to identify
      its protein constituents. Recent studies have used a combination of subcellular
      fractionation and proteomic techniques to identify proteins associated with
      different components of the synapse. Thus, a coherent map of the synapse proteome
      is rapidly emerging, and a timely review of these data is warranted. In the first
      part of this review, neuroproteomic techniques that have been used to analyze the
      synapse proteome are described. We then summarize the results from several recent
      proteomic analyses of mammalian synapses and discuss the similarities and
      differences in their profiling of synaptic proteins. Important advances in this
      field of research include the use of proteomics to analyze synaptic function and
      drug effects on synaptic proteins. This article presents an overview of proteomic
      analyses of the phosphorylation states of synaptic proteins and recent
      applications of neuroproteomic techniques to the study of drug addiction.
      Finally, we discuss the challenges in comparing proteomic studies of drug
      addiction and the future directions of this field in furthering our understanding
      of the molecular mechanisms underlying synaptic function and drug addiction.

PMID- 16644902
TI  - Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice.
AB  - This study investigated the blood glucose-lowering effect and antioxidant
      capacity of caffeic acid in C57BL/KsJ-db/db mice. Caffeic acid induced a
      significant reduction of the blood glucose and glycosylated hemoglobin levels
      than the control group. The plasma insulin, C-peptide, and leptin levels in
      caffeic acid group were significantly higher than those of the control group,
      whereas the plasma glucagon level was lower. Increased plasma insulin by caffeic
      acid was attributable to an antidegenerative effect on the islets. Caffeic acid
      also markedly increased glucokinase activity and its mRNA expression and glycogen
      content and simultaneously lowered glucose-6-phosphatase and phosphoenolpyruvate
      carboxykinase activities and their respective mRNA expressions, accompanied by a
      reduction in the glucose transporter 2 expression in the liver. In contrast to
      the hepatic glucose transporter 2, adipocyte glucose transporter 4 expression was
      greater than the control group. In addition, caffeic acid significantly increased
      superoxide dismutase, catalase, and glutathione peroxidase activities and their
      respective mRNA levels, while lowering the hydrogen peroxide and thiobarbituric
      acid reactive substances levels in the erythrocyte and liver of db/db mice. These
      results indicate that caffeic acid exhibits a significant potential as an
      antidiabetic agent by suppressing a progression of type 2 diabetic states that is
      suggested by an attenuation of hepatic glucose output and enhancement of
      adipocyte glucose uptake, insulin secretion, and antioxidant capacity.

PMID- 16644903
TI  - Pharmacological and molecular characterization of the mechanisms involved in
      prostaglandin E2-induced mouse paw edema.
AB  - The present study evaluated some of the mechanisms underlying prostaglandin E2
      (PGE2)-induced paw edema formation in mice. Intraplantar (i.pl.) injection of
      PGE2 (0.10-10.0 nmol/paw) into the hindpaw elicited a dose-related edema
      formation, with a mean ED50 value of 0.42 nmol/paw. The coinjection of selective
      E-prostanoid (EP)3 [(2E)-N-[(5-bromo-2-methoxyphenyl)-sulfonyl]-3-[5-chloro-2-(2
      naphthylmethyl)phenyl]acrylamide; L826266), but not EP2 or EP4 (all 10 nmol/paw),
      receptor antagonists significantly inhibited PGE2-induced paw edema. Like
      L826266, the PGE2-induced paw edema was markedly reduced by treatment with
      pertussis toxin and phospholipase C (PLC) inhibitor 1-[6-[[17beta-methoxyestra
      1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122). Likewise, the
      selective neurokinin (NK)1 receptor antagonist N-[(4R)-4-hydroxy-1-(1-methyl-1H
      indol-3-yl)carbonyl-l-prolyl]-N-methyl-N-phenyl-methyl-3-(2-aphthyl)-l
      alaninamide (FK888) and the antagonist of vanilloid receptor (TRPV1) receptors 4'
      chloro-3-methoxycinnamanilide (SB366791) (both 1 nmol/paw) also significantly
      inhibited PGE2-mediated paw edema. Conversely, the selective NK2, NK3, and
      calcitonin gene-related peptide (CGRP) CGRP(8-37) receptor antagonists all failed
      to interfere with PGE2-induced paw edema. The neonatal treatment of mice with
      capsaicin was also able to reduce PGE2-induced paw edema. The inhibitors of
      protein kinase C (PKC) 3-[1-[3-(dimethylaminopropyl]-1H-indol-3-yl]-4-(1H-indol-3
      yl)-1H-pyrrole-2,5-dione monohydrochloride (GF109203X) and mitogen protein
      activated kinases (MAPKs; 30 nmol/paw) c-Jun NH2-terminal kinase (JNK)
      (anthra[1,9-cd]pyrazol-6(2H)-one; SP600125), extracellular signal-regulated
      kinase (PD98059), and p38 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)1H-imidazole; SB203580], but not protein kinase A, markedly decreased the
      PGE2-mediated edema formation. The i.pl. injection of PGE2 (3 nmol/paw) induced a
      significant activation of MAPKs, namely, JNK and p38, an effect that was largely
      prevented by the selective EP3 receptor antagonist L826266 (10 nmol/paw).
      Collectively, these findings indicate that edematogenic responses elicited by
      PGE2 are mediated by EP3 receptor activation, also involving the stimulation of
      PLC, PKC, and MAPKs pathways and the participation of TRPV1 and NK1 receptors.
      These results make a considerable contribution to our comprehension of the
      mechanisms involved in PGE2-mediated inflammatory responses in mice.

PMID- 16644904
TI  - Amphetamine analogs increase plasma serotonin: implications for cardiac and
      pulmonary disease.
AB  - Elevations in plasma serotonin (5-HT) have been implicated in the pathogenesis of
      cardiac and pulmonary disease. Normally, plasma 5-HT concentrations are kept low
      by transporter-mediated uptake of 5-HT into platelets and by metabolism to 5
      hydroxyindoleacetic acid (5-HIAA). Many abused drugs (e.g., substituted
      amphetamines) and prescribed medications (e.g., fluoxetine) target 5-HT
      transporters and could thereby influence circulating 5-HT. We evaluated the
      effects of amphetamines analogs [(+/-)-fenfluramine, (+/-)-3,4
      methylenedioxymethamphetamine, (+)-methamphetamine, (+)-amphetamine, phentermine]
      on extracellular levels (i.e., plasma levels) of 5-HT and 5-HIAA in blood from
      catheterized rats. Effects of the 5-HT uptake blocker fluoxetine were examined
      for comparison. Drugs were tested in vivo and in vitro; plasma indoles were
      measured using a novel microdialysis method in whole blood. We found that
      baseline dialysate levels of 5-HT are approximately 0.22 nM, and amphetamine
      analogs evoke large dose-dependent increases in plasma 5-HT ranging from 4 to 20
      nM. The ability of drugs to elevate plasma 5-HT is positively correlated with
      their potency as 5-HT transporter substrates. Fluoxetine produced small, but
      significant, increases in plasma 5-HT. Although the drug-evoked 5-HT
      concentrations are below the micromolar levels required for contraction of
      pulmonary arteries, they approach concentrations reported to stimulate
      mitogenesis in pulmonary artery smooth muscle cells. Additional studies are
      needed to determine the effects of chronic administration of amphetamines on
      circulating 5-HT.

PMID- 16644905
TI  - Trends in the treatment of breast cancer in Southeast England following the
      introduction of national guidelines.
AB  - There is little published evidence on trends in the treatment of breast cancer in
      England following the publication of the Calman-Hine report in 1995. Reliable
      national data are available for women with screen-detected breast cancer, but
      data on women presenting symptomatically have been difficult to collect. Using
      data from both a clinical audit database and a population-based cancer register,
      we show that between 1996 and 2003 the rates of mastectomy and chemotherapy
      treatment for women with breast cancer in Southeast England have increased
      marginally, whereas there has been a steady decline in the use of hormone therapy
      and radiotherapy recorded within 6 months of diagnosis.

PMID- 16644906
TI  - Maternal glucocorticoids and prenatal programming of hypertension.
AB  - Maternal glucocorticoids have been postulated to play an important role in
      prenatal programming for adult hypertension in the offspring. However, we have
      shown previously that offspring hypertension caused by maternal dexamethasone
      subcutaneous administration at 100 microg x kg(-1) x day(-1) can be accounted for
      by the corresponding reduction in food intake that these mothers experience. The
      present studies were designed to determine whether there is a lower dose of
      dexamethasone that does not reduce maternal food intake yet still causes
      hypertension in the adult offspring. Pregnant rats were treated with subcutaneous
      dexamethasone at 50 (D50) or 25 (D25) microg x kg(-1) x day(-1) on days 15-20 of
      pregnancy. An additional group was untreated or received vehicle injections
      (control). D25 and D50 dams reduced their food intake by 17% during and after
      treatment and gained 31% less weight than control over the course of gestation.
      In adulthood ( approximately 21 wk), chronically instrumented male offspring of
      D50 and D25 had normal blood pressures (D50: 131 +/- 2 mmHg and D25: 127 +/- 3
      mmHg vs. 127 +/- 2 mmHg in control). Qualitatively similar results were found in
      female offspring. Thus neither dexamethasone per se at these doses nor the
      accompanying modest reductions in maternal food intake and weight gain have blood
      pressure programming effects. As far as has been tested, there does not appear to
      be a dose of dexamethasone that, given over this time period in the rat, programs
      offspring hypertension without reducing maternal food intake and weight gain.
      These data do not support the hypothesis that maternal glucocorticoids program
      offspring hypertension directly.

PMID- 16644907
TI  - Activation of adenosine A2A receptors alters postsynaptic currents and
      depolarizes neurons of the supraoptic nucleus.
AB  - Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to
      various physiological stimuli (e.g., lactation/suckling, dehydration). Released
      near fenestrated capillaries of the neurohypophysis, these peptides enter the
      blood and travel to peripheral target organs. The pervasive neuromodulator
      adenosine, acting at A1 receptors, is an important inhibitory regulator of
      magnocellular neuroendocrine cell activity. Another high-affinity adenosine
      receptor exists in this system, however. We examined the physiological effects of
      adenosine A2A receptor activation and determined its localization among various
      cell types within the SON. In whole cell patch-clamp recordings from rat brain
      slices, application of the selective adenosine A2A receptor agonist CGS-21680
      caused membrane depolarizations in SON neurons, often leading to increased firing
      activity. Membrane potential changes were persistent (>10 min) and could be
      blocked by the selective A2A receptor antagonist ZM-241385, or GDP-beta-S, the
      latter suggesting postsynaptic sites of action. However, +/--alpha-methyl-(4
      carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary
      actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680
      caused a slight increase (approximately 8%) in high-frequency clusters of
      excitatory postsynaptic currents. With the use of specific antibodies, adenosine
      A2A receptors were immunocytochemically localized to both the magnocellular
      neurons and astrocytes of the SON. Ecto-5'nucleotidase, an enzyme involved in the
      metabolism of ATP to adenosine, was also localized to astrocytes of the SON.
      These results demonstrate that adenosine acting at A2A receptors can enhance the
      excitability of SON neurons and modulate transmitter release from glutamatergic
      afferents projecting to the nucleus. We suggest that adenosine A2A receptors may
      function in neuroendocrine regulation through both direct neuronal mechanisms and
      via actions involving glia.

PMID- 16644908
TI  - Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin.
AB  - The interaction between ghrelin and bombesin or amylin administered
      intraperitoneally on food intake and brain neuronal activity was assessed by Fos
      like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 microg/kg ip)
      increased food intake compared with the vehicle group when measured at 30 min
      (g/kg: 3.66 +/- 0.80 vs. 1.68 +/- 0.42, P < 0.0087). Bombesin (8 microg/kg)
      injected intraperitoneally with ghrelin (13 microg/kg) blocked the orexigenic
      effect of ghrelin (1.18 +/- 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8
      microg/kg ip) exerted a dose-related nonsignificant reduction of food intake
      (g/kg: 1.08 +/- 0.44, P > 0.45 and 0.55 +/- 0.34, P > 0.16, respectively). By
      contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 +/- 0.56 g/kg
      vs. vehicle 0.82 +/- 0.59, P < 0.004) was not altered by amylin (1 and 5
      microg/kg ip) (g/kg: 4.37 +/- 1.12, P > 0.69, and 3.01 +/- 0.78, respectively, P
      > 0.37). Ghrelin increased the number of FLI-positive neurons/section in the
      arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008).
      Bombesin alone (4 and 8 microg/kg ip) did not induce FLI neurons in the
      paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin
      did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 microg/kg)
      with ghrelin significantly increased neuronal activity in the PVN approximately
      threefold compared with vehicle and approximately 1.5-fold compared with the
      ghrelin group. Bombesin (8 microg/kg) with ghrelin injected intraperitoneally
      induced Fos expression in 22.4 +/- 0.8% of CRF-immunoreactive neurons in the PVN.
      These results suggest that peripheral bombesin, unlike amylin, inhibits
      peripheral ghrelin induced food intake and enhances activation of CRF neurons in
      the PVN.

PMID- 16644910
TI  - Locus coeruleus is a central chemoreceptive site in toads.
AB  - The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in
      mammals. This nucleus is a mesencephalic structure of the amphibian brain and is
      probably homologous to the LC in mammals. There are no data available for the
      role of LC in the central chemoreception of amphibians. Thus the present study
      was designed to investigate whether LC of toads (Bufo schneideri) is a CO2/H+
      chemoreceptor site. Fos immunoreactivity was used to verify whether the nucleus
      is activated by hypercarbia (5% CO2 in air). In addition, we assessed the role of
      noradrenergic LC neurons on respiratory and cardiovascular responses to
      hypercarbia by using 6-hydroxydopamine lesion. To further explore the role of LC
      in central chemosensitivity, we examined the effects of microinjection of
      solutions with different pH values (7.2, 7.4, 7.6, 7.8, and 8.0) into the
      nucleus. Our main findings were that 1) a marked increase in c-fos-positive cells
      in the LC was induced after 3 h of breathing a hypercarbic gas mixture; 2)
      chemical lesions in the LC attenuated the increase of the ventilatory response to
      hypercarbia but did not affect ventilation under resting conditions; and 3)
      microinjection with acid solutions (pH = 7.2, 7.4, and 7.6) into the LC elicited
      an increased ventilation, indicating that the LC of toads participates in the
      central chemoreception.

PMID- 16644911
TI  - Outcome of ICSI with ejaculated spermatozoa in a series of men with distinct
      ultrastructural flagellar abnormalities.
AB  - BACKGROUND: Severe sperm motility impairment results in human infertility, which
      can be overcome by ICSI. Whether some particular, possibly genetic, flagellar
      abnormalities can influence embryonic development is a matter of debate. METHODS:
      Analysis of ultrastructural flagellar abnormalities and ICSI outcomes with
      ejaculated spermatozoa in a series of 21 infertile patients with
      asthenozoospermic or dyskinetic spermatozoa due to a primary and specific
      flagellar abnormality was carried out. RESULTS: Patients were sorted into six
      categories according to flagellar ultrastructural defects. Oocyte fertilization
      occurred in the 21 couples with a mean 2PN fertilization rate reaching 61.85%. No
      difference was observed in the kinetics of in vitro development or in the
      morphological quality of the embryos between the different types of flagellar
      abnormalities. Pregnancy occurred in 12 couples (57.1%) and delivery in nine
      couples (42.86%). Both the implantation rate and the clinical pregnancy rate per
      cycle were lower in type III abnormalities and in patients with an initial sperm
      motility less than 5%. CONCLUSIONS: The rate of ICSI success may be influenced by
      the type of flagellar abnormality. ICSI provides a suitable solution for patients
      with sperm flagellar defects but raises the question of the consequences of a
      specific (and primary flagellar) abnormality on oocyte fertilization, on embryo
      and fetal development as well as on live birth.

PMID- 16644912
TI  - Recurrence of ovarian endometrioma after laparoscopic excision.
AB  - BACKGROUND: To analyse risk factors that influence the recurrence of endometrioma
      after laparoscopic excision. METHODS: A total of 224 patients who had a minimum
      of 2 years of post-operative follow-up after laparoscopic ovarian endometrioma
      excision were studied retrospectively. Recurrence was defined as the presence of
      endometrioma more than 2 cm in size, detected by ultrasonography within 2 years
      of surgery. Fourteen variables (age, presence of infertility, pain, uterine
      myoma, adenomyosis, previous medical treatment of endometriosis, previous surgery
      for ovarian endometriosis, single or multiple cysts, the size of the largest cyst
      at laparoscopy, unilateral or bilateral involvement, co-existence of deep
      endometriosis, revised American Society for Reproductive Medicine (ASRM) score,
      post-operative medical treatment and post-operative pregnancy) were evaluated to
      assess their independent effects on the recurrence using logistic regression
      analysis. RESULTS: The overall rate of recurrence was 30.4% (68/224). Significant
      factors that were independently associated with higher recurrence were previous
      medical treatment of endometriosis [odds ratio (OR) = 2.324, 95% confidence
      interval (95% CI) = 1.232-4.383, P = 0.0092) and larger diameter of the largest
      cyst (OR = 1.182, 95% CI = 1.004-1.391, P = 0.0442). Post-operative pregnancy was
      associated with lower recurrence (OR = 0.292, 95% CI = 0.028-0.317, P = 0.0181).
      CONCLUSIONS: Previous medical treatment of endometriosis or large cyst size was a
      significant factor that was associated with higher recurrence of the disease.
      Post-operative pregnancy is a favourable prognostic factor.

PMID- 16644913
TI  - A randomized double-blind controlled study on the efficacy of laser zona
      pellucida thinning on live birth rates in cases of advanced female age.
AB  - BACKGROUND: It is conceivable that defective embryo hatching plays a part in the
      mechanisms involved in the decrease of embryo implantation rates with advancing
      age. In an effort to test this hypothesis, we tested the effectiveness of
      assisted hatching (AH) in women > or =37 years of age. METHODS: We prospectively
      studied 103 IVF-embryo transfer patients undergoing 103 embryo transfers. All of
      them were > or =37 years of age and had <3 previous IVF-embryo transfer attempts.
      Laser-AH of transferred embryos was either performed (AH group, n = 49) or not
      (control group, n = 54) according to randomized and double-blind methodology.
      Primary outcome was live birth rate. RESULTS: Population characteristics were
      comparable in AH and control groups as well as the mean number of embryos
      transferred (2.7 +/- 0.6 versus 2.7 +/- 0.6) and the prevalence of top quality
      embryos transferred (65 versus 59%, respectively). We failed to find any
      statistically significant difference between AH and control groups with regard to
      implantation (16.1 versus 16.7%, respectively) and live birth rates (22.4 versus
      29.6%, respectively). CONCLUSION: The present study indicates that AH does not
      improve IVF-embryo transfer outcome in women aged > or =37 years.

PMID- 16644914
TI  - Engineered antibody-drug conjugates with defined sites and stoichiometries of
      drug attachment.
AB  - The chimeric anti-CD30 IgG1, cAC10, conjugated to eight equivalents of monomethyl
      auristatin E (MMAE) was previously shown to have potent antitumor activity
      against CD30-expressing tumors xenografts in mice. Moreover, the therapeutic
      index was increased by lowering the stoichiometry from 8 drugs/antibody down to 2
      or 4. Limitations of such 'partially-loaded' conjugates are low yield (10-30%) as
      they are purified from mixtures with variable stoichiometry (0-8 drugs/antibody),
      and heterogeneity as the 2 or 4 drugs are distributed over eight possible
      cysteine conjugation sites. Here, the solvent-accessible cysteines that form the
      interchain disulfide bonds in cAC10 were replaced with serine, to reduce the
      eight potential conjugation sites down to 4 or 2. These Cys-->Ser antibody
      variants were conjugated to MMAE in near quantitative yield (89-96%) with defined
      stoichiometries (2 or 4 drugs/antibody) and sites of drug attachment. The
      engineered antibody-drug conjugates have comparable antigen-binding affinities
      and in vitro cytotoxic activities with corresponding purified parental antibody
      drug conjugates. Additionally, the engineered and parental antibody-drug
      conjugates have similar in vivo properties including antitumor activity,
      pharmacokinetics and maximum tolerated dose. Our strategy for generating antibody
      drug conjugates with defined sites and stoichiometries of drug loading is
      potentially broadly applicable to other antibodies as it involves engineering of
      constant domains.

PMID- 16644915
TI  - Role of the exchange protein directly activated by cyclic adenosine 5'
      monophosphate (Epac) pathway in regulating proglucagon gene expression in
      intestinal endocrine L cells.
AB  - Although proglucagon gene expression and the synthesis of proglucagon encoded
      peptide hormones could be activated by protein kinase A (PKA) activators such as
      forskolin/3-isobutyl-1-methylxanthine (IBMX) and cholera toxin, whether the
      activation is entirely attributed to PKA has not been previously examined. We
      found that forskolin/IBMX also activate ERK1/2 phosphorylation in intestinal and
      pancreatic proglucagon-producing cell lines. The MEK inhibitors PD98059 and U0126
      were found to repress the expression of proglucagon promoter as well as
      endogenous proglucagon mRNA in two intestinal proglucagon-producing cell lines
      and to block the stimulatory effect of forskolin/IBMX on proglucagon mRNA
      expression. The repressive effect of the PKA-specific inhibitors H-89 and KT
      5720, however, was either not observable or much less potent. Forskolin could
      activate ERK1/2 phosphorylation and proglucagon gene transcription on its own,
      whereas forskolin plus IBMX are required to effectively activate the PKA pathway
      in the proglucagon-producing cells. Exchange protein directly activated by cyclic
      AMP 2 (Epac2, or cAMP-binding guanine nucleotide exchange factor-2) was found to
      be expressed in gut and pancreatic proglucagon-producing cell lines, whereas the
      Epac-pathway-specific cAMP analog, 8-pMeOPT-2'O-Me-cAMP, effectively stimulated
      ERK1/2 phosphorylation as well as proglucagon mRNA expression. We therefore
      suggest that cAMP at least partially regulates proglucagon gene expression via
      the Epac-Ras/Rap-Raf-MEK-ERK signaling pathway.

PMID- 16644916
TI  - Role of insulin receptor in the regulation of glucose uptake in neonatal
      hepatocytes.
AB  - The liver plays a major role in the regulation of glucose homoeostasis. Evidence
      from liver-specific insulin receptor knockout mice (LIRKO) suggested that
      insulin's direct and indirect effects on glucose utilization by the liver both
      require the presence of hepatic insulin receptors (IR). To address this issue, we
      have generated immortalized neonatal hepatocytes bearing (HIR LoxP) or not (HIR
      KO) IR. The lack of IR significantly decreased basal glucose uptake in neonatal
      hepatocytes from 3- to 14-d-old mice, and the expression of glucose transporter 1
      (GLUT1), GLUT2, and glucokinase (GK) remained unchanged throughout development.
      HIR KO reconstituted hepatocytes with IRA but not with IRB isoform and restored
      basal glucose uptake up to the levels observed in HIR LoxP cells. However, both
      IR isoforms associated with GLUT1 or GLUT2. Overexpression of IGF-I receptor (IGF
      IR) increased basal glucose uptake in neonatal hepatocytes lacking or not IR.
      This effect was also accompanied by its association with GLUT1 or GLUT2.
      Exogenous expression of GLUT4 had no effect on basal glucose uptake in neonatal
      hepatocytes. However, HIR LoxP hepatocytes expressing exogenous GLUT4 increased
      glucose uptake in the presence of insulin without showing association between
      GLUT4 and IR. Our data clearly indicate that IR plays a direct role in the
      regulation of basal glucose uptake/transport by the hepatocytes, and either type
      A IR or IGF-IR works on glucose uptake as a GLUT1- or GLUT2-associated
      cotransporter. Thus, IR mediates glucose uptake through its specific association
      with endogenous, but not with exogenous, glucose transporters in neonatal
      hepatocytes.

PMID- 16644917
TI  - Sterol regulatory element-binding protein 1 mediates liver X receptor-beta
      induced increases in insulin secretion and insulin messenger ribonucleic acid
      levels.
AB  - Liver X receptors (LXRalpha and LXRbeta) regulate glucose and lipid metabolism.
      Pancreatic beta-cells and INS-1E insulinoma cells express only the LXRbeta
      isoform. Activation of LXRbeta with the synthetic agonist T0901317 increased
      glucose-induced insulin secretion and insulin content, whereas deletion of the
      receptor in LXRbeta knockout mice severely blunted insulin secretion. Analysis of
      gene expression in LXR agonist-treated INS-1E cells and islets from LXRbeta
      deficient mice revealed that LXRbeta positively regulated expression of ATP
      binding cassette transporter A1 (ABCA1), sterol regulatory element-binding
      protein 1 (SREBP-1), insulin, PDX-1, glucokinase, and glucose transporter 2
      (Glut2). Down-regulation of SREBP-1 expression with the specific small
      interfering RNA blocked basal and LXRbeta-induced expression of pancreatic
      duodenal homeobox 1 (PDX-1), insulin, and Glut2 genes. SREBP-1 small interfering
      RNA also prevented an increase in insulin secretion and insulin content induced
      by T0901317. Moreover, 5-(tetradecyloxy)-2-furoic acid, an inhibitor of the SREBP
      1 target gene acetyl-coenzyme A carboxylase, blocked T0901317-induced stimulation
      of insulin secretion. In conclusion, activation of LXRbeta in pancreatic beta
      cells increases insulin secretion and insulin mRNA expression via SREBP-1
      regulated pathway. These data support the role of LXRbeta, SREBP-1, and
      cataplerosis/anaplerosis pathways in the control of insulin secretion in
      pancreatic beta-cells.

PMID- 16644918
TI  - Postnatal remodeling of dendritic structure and spine density in gonadotropin
      releasing hormone neurons.
AB  - The GnRH neurons represent the output cells of the neuronal network controlling
      gonadal function. Their activation initiates the onset of puberty, but the
      underlying mechanisms remain unclear. Using a GnRH-green fluorescent protein
      mouse model, we have been able to fill individual GnRH neurons with biocytin in
      the acute brain slice preparation to examine their morphological characteristics
      across puberty. GnRH neurons in prepubertal male mice [postnatal d 10-15 (PND10
      15)] exhibited half as many dendritic and somal spines as adult male mice
      (>PND60; P < 0.05) but, surprisingly, a much more complex dendritic tree with 5
      fold greater branch points (P < 0.05). Experiments examining somal and proximal
      dendritic spine numbers in vivo, in perfusion-fixed tissue from GnRH-green
      fluorescent protein mice, revealed the same pattern of approximately twice as
      many spines on adult GnRH neurons compared with PND10 male mice (P < 0.01). In
      contrast to the spine density alterations, reflecting changing excitatory input,
      confocal immunofluorescence studies revealed no differences in the numbers of
      vesicular gamma-aminobutyric acid transporter-immunoreactive elements adjacent to
      GnRH soma or proximal dendrites in prepubertal and adult male mice. Experiments
      evaluating dendritic tree structure in vivo (PND3, -10, and -35 and adult)
      revealed that GnRH neurons located in the rostral preoptic area, but not the
      medial septum, exhibited a more complex branching pattern at PND10, but that this
      was adult-like by PND35. These studies demonstrate unexpected dendritic tree
      remodeling in the GnRH neurons and provide evidence for an increase in direct
      excitatory inputs to GnRH neurons across the time of puberty.

PMID- 16644919
TI  - Differentiation of human embryonic stem cells into bipotent mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitors that can be found in
      many connective tissues, including fat, bone, cartilage, and muscle. We report
      here a method to reproducibly differentiate human embryonic stem cells (hESCs)
      into MSCs that does not require the use of any feeder layer. The cells obtained
      with this procedure are morphologically similar to bone marrow MSCs, are contact
      inhibited, can be grown in culture for about 20 to 25 passages, have an
      immunophenotype similar to bone marrow MSCs (negative for CD34 and CD45 and
      positive for CD13, CD44, CD71, CD73, CD105, CD166, human leukocyte antigen [HLA]
      ABC, and stage-specific embryonic antigen [SSEA]-4), can differentiate into
      osteocytes and adipocytes, and can be used as feeder cells to support the growth
      of undifferentiated hESCs. The ability to produce MSCs from hESCs should prove
      useful to produce large amounts of genetically identical and genetically
      modifiable MSCs that can be used to study the biology of MSCs and for therapeutic
      applications.

PMID- 16644920
TI  - Proximal prostatic stem cells are programmed to regenerate a proximal-distal
      ductal axis.
AB  - Prostate carcinoma and benign prostatic hypertrophy may both originate in stem
      cells, highlighting the importance of the characterization of these cells. The
      prostate gland contains a network of ducts each of which consists of a proximal
      (adjacent to the urethra), an intermediate, and a distal region. Here, we report
      that two populations of cells capable of regenerating prostatic tissue in an in
      vivo prostate reconstitution assay are present in different regions of prostatic
      ducts. The first population (with considerable growth potential) resides in the
      proximal region of ducts and in the urethra, and the survival of these cells does
      not require the presence of androgens. The second population (with more limited
      growth potential) is found in the remaining ductal regions and requires androgen
      for survival. In addition, we find that primitive proximal prostate cells that
      are able to regenerate functional prostatic tissue in vivo are also programmed to
      re-establish a proximal-distal ductal axis. Similar to their localization in the
      intact prostate, cells with the highest regenerative capacity are found in the
      proximal region of prostatic ducts formed in an in vivo prostate reconstitution
      assay. The primitive proximal cells can be passaged through four generations of
      subrenal capsule grafts. Together, these novel findings illustrate features of
      primitive prostate cells that may have implications for the development of
      therapies for treating proliferative prostatic diseases.

PMID- 16644921
TI  - Mouse embryonic stem cells form follicle-like ovarian structures but do not
      progress through meiosis.
AB  - Several recent studies have suggested that mouse embryonic stem cells (ESCs) can
      differentiate into female and male germ cells in vitro. The meiotic process in
      germ cell-like cells derived from ESCs has not been studied in detail, but it has
      been reported that synaptonemal complex protein-3 (SYCP3) is expressed in these
      cells. Here, we have carefully evaluated the meiotic process in germ cell-like
      cells derived from ESCs, using a panel of meiosis-specific markers that identify
      distinct meiotic signatures unique to meiotic prophase I development in vivo. We
      find that whereas SYCP3 is expressed in germ cell-like cells, other meiotic
      proteins, such as SYCP1, SYCP2, STAG3 (stromal antigen 3), REC8 (meiotic protein
      similar to the rad21 cohesins), and SMC1 (structural maintenance of chromosomes
      1)-beta, are not expressed. The nuclear distribution of SYCP3 in the germ cell
      like cells is highly abnormal and not associated with the chromosomes of these
      cells. Fluorescence in situ hybridization analysis shows that the SYCP3-positive
      germ cell-like cells do not contain synapsed homologous chromosomes but instead
      display a chromosomal organization normally found in somatic cells. The absence
      of expression of essential meiotic proteins and a normal meiotic chromosomal
      organization strongly suggests that the germ cell-like cells formed from ESCs
      fail to progress through meiosis.

PMID- 16644922
TI  - Combined immunosuppressive agents or CD4 antibodies prolong survival of human
      neural stem cell grafts and improve disease outcomes in amyotrophic lateral
      sclerosis transgenic mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a target for cell-replacement therapies,
      including therapies based on human neural stem cells (NSCs). These therapies must
      be first tested in the appropriate animal models, including transgenic rodents
      harboring superoxide dismutase (SOD1) mutations linked to familial ALS. However,
      these rodent subjects reject discordant xenografts. In the present investigation,
      we grafted NSCs from human embryonic spinal cord into the ventral lumbar cord of
      2-month-old SOD1-G93A transgenic mice. Animals were immunosuppressed with FK506,
      FK506 plus rapamycin, FK506 plus rapamycin plus mycophenolate mofetil, or CD4
      antibodies. With FK506 monotherapy, human NSC grafts were rejected within 1 week,
      whereas combinations of FK506 with one or two of the other agents or CD4
      antibodies protected grafts into end-stage illness (i.e., more than 2 months
      after grafting). The combination of FK506 with rapamycin appeared to be optimal
      with respect to efficacy and simplicity of administration. Graft protection was
      achieved via the blockade of CD4- and CD8-cell infiltration and attenuation of
      the microglial phagocytic response from the host. Surviving NSCs differentiated
      extensively into neurons that began to establish networks with host nerve cells,
      including alpha-motor neurons. Immunosuppressed animals with live cells showed
      later onset and a slower progression of motor neuron disease and lived longer
      compared with immunosuppressed control animals with dead NSC grafts. Our findings
      indicate that combined immunosuppression promotes the survival of human NSCs
      grafted in the spinal cord of SOD1-G93A mice and, in doing so, allows the
      differentiation of NSCs into neurons and leads to the improvement of key
      parameters of motor neuron disease.

PMID- 16644923
TI  - High yield of cells committed to the photoreceptor fate from expanded mouse
      retinal stem cells.
AB  - The purpose of the present work was to generate, from retinal stem cells (RSCs),
      a large number of cells committed toward the photoreceptor fate in order to
      provide an unlimited cell source for neurogenesis and transplantation studies. We
      expanded RSCs (at least 34 passages) sharing characteristics of radial glial
      cells and primed the cells in vitro with fibroblast growth factor (FGF)-2 for 5
      days, after which cells were treated with the B27 supplement to induce cell
      differentiation and maturation. Upon differentiation, cells expressed cell type
      specific markers corresponding to neurons and glia. We show by
      immunocytochemistry analysis that a subpopulation of differentiated cells was
      committed to the photoreceptor lineage given that these cells expressed the
      photoreceptor proteins recoverin, peripherin, and rhodopsin in a same ratio.
      Furthermore, cells infected during the differentiation procedure with a
      lentiviral vector expressing green fluorescent protein (GFP) under the control of
      either the rhodopsin promoter or the interphotoreceptor retinoid-binding protein
      (IRBP) promoter, expressed GFP. FGF-2 priming increased neuronal differentiation
      while decreasing glia generation. Reverse transcription-polymerase chain reaction
      analyses revealed that the differentiated cells expressed photoreceptor-specific
      genes such as Crx, rhodopsin, peripherin, IRBP, and phosphodiesterase-alpha.
      Quantification of the differentiated cells showed a robust differentiation into
      the photoreceptor lineage: Approximately 25%-35% of the total cells harbored
      photoreceptor markers. The generation of a significant number of
      nondifferentiated RSCs as well as differentiated photoreceptors will enable
      researchers to determine via transplantation studies which cells are the most
      adequate to integrate a degenerating retina.

PMID- 16644924
TI  - Flt3-ligand-mobilized peripheral blood, but not Flt3-ligand-expanded bone marrow,
      facilitating cells promote establishment of chimerism and tolerance.
AB  - Facilitating cells (CD8+/TCR-) (FCs) enhance engraftment of limiting numbers of
      hematopoietic stem cells (HSCs). The primary component of FCs is precursor
      plasmacytoid dendritic cells (p-preDCs), a tolerogenic cell expanded by Flt3
      ligand (FL). In this study, we evaluated the function and composition of FL
      expanded FCs. FL treatment resulted in a significant increase of FCs in bone
      marrow (BM) and peripheral blood (PB). When FL-expanded FCs were transplanted
      with c-Kit+/Sca-1+/Lin- (KSL) cells into allogeneic recipients, BM-FCs exhibited
      significantly impaired function whereas PB-FCs were potently functional. A
      significant upregulation of P-selectin expression and downregulation of VCAM-1
      (vascular cell adhesion molecule 1) were present on FL-expanded PB-FCs compared
      with FL BM-FCs. Stromal cell-derived factor-1 (SDF-1), and CXCR4 transcripts were
      significantly increased in FL PB-FCs and decreased in FL BM-FCs. Supernatant from
      FL PB-FCs primed HSC migration to SDF-1, confirming production of the protein
      product. The FL PB-FCs contained a predominance of p-preDCs and natural killer
      (NK)-FCs, and NK-FCs were lacking in FL BM-FCs. The impaired function for BM-FCs
      was restored within 5 days after cessation of treatment. Taken together, these
      data suggest that FCs may enhance HSC homing and migration via the SDF-1/CXCR4
      axis and adhesion molecule modulation. These findings may have implications in
      development of strategies for retaining function of ex vivo manipulated FCs and
      HSCs.

PMID- 16644925
TI  - In vitro characteristics and in vivo immunosuppressive activity of compact bone
      derived murine mesenchymal progenitor cells.
AB  - In contrast to the considerable amount of data that documents the biological
      properties of mesenchymal progenitor cells from human and other species, there is
      still paucity of information about mouse counterparts, as their purification and
      culture expansion procedures remain rudimentary. In the present study, murine
      mesenchymal progenitor cell (muMPC) culture was developed by explant culture of
      collagenase-digested bone fragments after removal of the released cells. During
      cultivation, fibroblastoid cells sprouted and migrated from the fragments,
      followed by adherent monolayer development. The cells exhibited homogenous
      surface antigen profile and presented in vitro multipotential differentiation
      along osteocyte, chondrocyte, and adipocyte lineages, as evaluated by matched
      cell or matrix staining and reverse transcription polymerase chain reaction
      techniques. Also, the surface antigenic epitope changed and potential of
      proliferation and multidifferentiation decreased with successive subculturing.
      Functional investigations demonstrated that these cells supported in vitro
      hematopoiesis and suppressed lymphocyte cell proliferation triggered by ConA or
      allogeneic splenocytes. Furthermore, muMPCs prolonged the mean survival time of
      skin grafts across the major histocompatibility barrier (H2(b) --> H2(d)),
      suggestive of the immunosuppressive effects in vivo. The findings demonstrate
      that muMPCs obtained with this simple protocol are similar in property to their
      marrow counterparts, and thus, the protocol described here could be used for
      further investigations in mouse physiological and pathological models.

PMID- 16644926
TI  - Perceived health status and use of healthcare services among children and
      adolescents.
AB  - BACKGROUND: The aim of the present study was to analyse the use of healthcare
      services according to health status in a population of children and adolescents,
      taking into account family socio-demographic characteristics and characteristics
      of the proxy respondent. METHODS: A total of 836 interviews of proxy respondents
      for children aged 5-14 years from the Barcelona Health Interview Survey carried
      out in 2000 were included. Dependent variables were visits to a healthcare
      professional, visits to the emergency room, and hospitalization. Independent
      variables were: report of medical conditions, health status of the child measured
      by the Child Health and Illness Profile-Child Edition, Parent Report Form (CHIP
      CE/PRF), the educational level of the head of household, social class, child's
      healthcare coverage, and proxy-related variables [mental health status by means
      of the General Health Questionnaire-12 items version (GHQ-12), and other].
      Logistic regression analysis was used to estimate prevalence ratio (PR) to
      compare the use of healthcare services among different categories of independent
      variables. RESULTS: Children having worse health status were more likely to have
      visited a healthcare professional [PR = 1.68; 95% confidence interval (95% CI) =
      1.09-3.83], whereas children with a reported medical condition were more likely
      to have made a visit to the emergency service (PR = 1.47; 95% CI = 1.27-2.55) and
      were hospitalized more frequently (PR = 2.50; 95% CI = 1.12-5.57). Higher
      likelihood of visits to the emergency room was associated with children having
      both public and private coverage and a proxy respondent scoring 3 or higher on
      the GHQ-12. CONCLUSIONS: Use of healthcare services differed by health needs but
      not by social class. Double healthcare coverage and mental distress of the proxy
      respondent influenced the use of emergency services.

PMID- 16644927
TI  - Heatwaves and public health in Europe.
AB  - Public health measures need to be implemented to prevent heat-related illness and
      mortality in the community and in institutions that care for elderly or
      vulnerable people. Heat health warning systems (HHWS) link public health actions
      to meteorological forecasts of dangerous weather. Such systems are being
      implemented in Europe in the absence of strong evidence of the effectiveness of
      specific measures in reducing heatwave mortality or morbidity. Passive
      dissemination of heat avoidance advice is likely to be ineffective given the
      current knowledge of high-risk groups. HHWS should be linked to the active
      identification and care of high-risk individuals. The systems require clear lines
      of responsibility for the multiple agencies involved (including the weather
      service, and the local health and social care agencies). Other health
      interventions are necessary in relation to improved housing, and the care of the
      elderly at home and vulnerable people in institutions. European countries need to
      learn from each other how to prepare for and effectively cope with heatwaves in
      the future. Including evaluation criteria in the design of heatwave early warning
      systems will help ensure effective and efficient system operation.

PMID- 16644928
TI  - Russian medicine and the Nuremberg trials.

PMID- 16644929
TI  - A TL-based anthropomorphic benchmark for verifying 3-D dose distributions from
      external electron beams calculated by radiotherapy treatment planning systems.
AB  - Initial results are reported of a Polish-Finnish project to verify electron dose
      distributions calculated by treatment planning systems (TPSs), CadPlan v.6.3.2
      and Theraplan v.3.5, which use different electron beam dose distribution
      algorithms. Treatment of gross tumour volumes representing lung and parotid
      cancer was simulated in an Alderson anthropomorphic phantom with
      thermoluminescent detectors (TLDs) (Li(2)B(4)O(7):Mn,Si) placed at selected
      measurement points inside its volume. The observed discrepancy between relative
      values of dose calculated and measured by TLDs at each of the measurement points
      and those calculated by the different TPSs at the same points is discussed.

PMID- 16644930
TI  - A family of statistical distributions for modelling occupational radiation doses
      in low dose occupations.
AB  - New statistical distributions have been defined to describe occupational
      exposures to ionising radiation. These distributions are particularly useful in
      modelling occupations where most doses are low. The maximum likelihood method was
      used for parameter estimation and has been adapted to allow doses that are
      recorded as zero to be included in the calculations. The method can then be
      applied to estimate true doses from the complete set of recorded dose values when
      the a priori dose distribution and the dose measurement distributions have been
      derived previously. This application is important in epidemiological cohort
      studies where it can improve the accuracy of excess relative risk estimates.

PMID- 16644931
TI  - A new methodology for the assessment of hand protection from ultraviolet
      exposure.
AB  - A number of industrial applications and public services involve occupational
      exposure to ultraviolet radiation (UVR) from a variety of lamps and lasers. The
      aim of this study was to develop a methodology for the assessment of the UV
      protection level for disposable gloves. Glove UV protection factor is defined as
      a time-scale increase in exposure permitted for the hand protected by a glove
      with respect to an unprotected hand. Our study showed that for all tested gloves
      a change in UVR attenuation with stretching is characteristic for the type of
      glove material and can be included as a scaling factor in the definition of UVR
      protection. Glove material has a bigger effect on UVR protection level than
      variations in the glove thickness or its colour. Examples of assessment of the
      'worst case scenario' are compared with the protection level against a number of
      sources, together with the guidance on a simplified evaluation protocol. An
      application-specific assessment, illustrated for 'SmartWater' forensic
      examinations and biological trans-illuminators, demonstrates that some gloves
      provide inadequate protection against occupational UV exposure.

PMID- 16644932
TI  - Evaluation of the EDR-2 film for relative dosimetry of high-energy photon and
      electron beams.
AB  - A sensitometric study of Kodak XV and EDR-2 radiographic films (Eastman Kodak
      Company, Rochester, NY) was performed using photons ranging from 75 kV to 18 MV
      and electrons ranging from 6 to 20 MeV. To investigate the applicability of the
      EDR-2 film for clinical radiation dosimetry, percentage depth-doses, profiles and
      distributions in open and dynamically wedged fields were measured using film and
      compared with data from a linear diode. Moreover, conventional quality assurance
      dose parameters were measured, including open-field dose profiles to determine
      flatness and symmetry of photon and electron beams. Finally, film was employed to
      validate dose distributions produced by complex computerised treatment planning
      techniques. Our conclusion is that the EDR-2 film is an effective tool for
      relative dosimetry of photon and electron beams.

PMID- 16644933
TI  - Comparison of the distribution of doses summarised over different periods of
      time.
AB  - Track dosemeters are very useful devices for dose assessment. The low cost and
      relatively simple procedures of dose calculation allow the mass distribution of
      track dosemeters in the population of exposed people. Because of the large number
      of measurements, observations may be made that would not be possible if the
      number of measurements were low. One such observation is the unexpected
      difference between the parameters of the annual dose distribution and the
      distribution of short-term doses. This difference may have a strong impact on
      lifetime dose or risk calculations. Much epidemiological data are based on the
      extrapolation of the distribution of short-term doses into the distribution of
      the lifetime dose. How the distribution of lifetime doses is spread is more
      complicated. The answer depends on the period of the single measurement.

PMID- 16644934
TI  - The sunlight OSL response of a commercially available alpha-Al2O3:C personnel
      dosimetry material.
AB  - Carbon-doped, anion-defective aluminium oxide has become a widely used and
      effective medium for personnel dosimetry applications using optically stimulated
      luminescence (OSL) techniques. Though the commercial products currently using
      this material employ light-tight packaging to prevent light-induced effects on
      the OSL signal, the material could be employed in environments where package
      integrity cannot be assured. This paper reports on the results of an experiment
      performed to quantify the effects of sunlight exposure on alpha-Al2O3:C. Samples
      of commercially available Luxel material were exposed to carefully recorded
      levels of sunlight both before and after irradiations to determine the nature and
      magnitude of both activation and fading phenomena in this material. The results
      confirm that both fading and activation processes are seen in this material and
      indicate that the material reaches an equilibrium dose level in response to
      prolonged sunlight exposure equivalent to a dose of approximately 15 mGy under
      the experimental test conditions.

PMID- 16644935
TI  - The simple SDD.
AB  - We describe the fabrication and characterisation of the SIMPLE superheated
      droplet detector, a 10 g active mass device of C(2)ClF(5) in 1-3% weight
      concentrations currently employed in a direct search for spin-dependent
      astroparticle dark matter candidates.

PMID- 16644936
TI  - Superheated drop neutron detectors used at the ESRF.
AB  - The ESRF operates a 6 GeV electron storage ring to produce X-rays. The
      experimental hall is classified as a free access area in terms of radiation
      protection. Interlocked radiation monitors guarantee the corresponding dose
      constraint. Measurements have shown that the radiation field outside the storage
      ring is dominated by neutrons. Apfel REMbrandt superheated drop detectors have
      been chosen. In total, 64 monitors are installed around the storage ring,
      interlocked to the accelerator personnel safety system. Since the radiation
      fields are highly pulsed, the response of the REMbrandt monitors to pulsed
      radiation was measured and compared with theoretical predictions. Dose recordings
      from the bubble detectors are shown, illustrating the good correlation between
      beam losses and dose rates, as well as showing the correspondence between neutron
      and photon dose values. Finally, around the beamline hutches, REMbrandt neutron
      monitors have been used to evaluate the ratio between neutron and photon dose
      rates.

PMID- 16644937
TI  - Etched tracks and serendipitous dosimetry.
AB  - Nuclear tracks in detectors that just happened to be there can be found in
      unexpected places. Eyeglasses, household glass, minerals, objects that were
      exposed to nuclear explosions, and space equipment on the moon are examples. Such
      materials allow us to measure doses of past radon exposures, cosmic-ray fluences,
      fission rates and neutrons. Incidental results include measuring mountain
      building rates and deciding where finding oil is likely (or unlikely); in another
      case erosion rates of surface materials in space are found. New results that
      assess the effects of hydration layers on the leaching out from glass surfaces of
      imbedded alpha-recoil nuclei imply that long-term, retrospective radon
      measurements can be made more reliable by selecting only glass with compact
      hydration layers.

PMID- 16644938
TI  - Highly sensitive thermoluminescent carbon doped nanoporous aluminium oxide
      detectors.
AB  - In this work we present the synthesis, characterisation and the
      thermoluminescence (TL) response of nanoporous carbon doped aluminium oxide
      Al2O3:C produced by anodic oxidation of aluminium in organic and inorganic
      solvents. The X-ray and scanning electron microscopy (SEM) measurements reveal
      that the synthesised samples are amorphous and present highly ordered structures
      with uniform pore distribution with diameter of the order 50 nm. The
      photoluminescence and spectroscopic analysis in the visible and infrared regions
      show that the luminescence properties presented by the samples prepared in
      organic acid are due to carboxylate species, incorporated in anodic alumina films
      during the synthesis process. After an annealing treatment, part of the
      incorporated species decomposes and is incorporated into the structure of the
      aluminium oxide yielding a highly thermoluminescent detector (TL) . The results
      for X-ray irradiation in the range from 21 to 80 keV indicate a linear TL
      response with the dose in the range from 5 mGy to 1 Gy, suggesting that
      nanoporous aluminium oxide produced in the present route of synthesis is a
      suitable detector for radiation measurements.

PMID- 16644939
TI  - Ion diffusion modelling of Fricke-agarose dosemeter gels.
AB  - In Fricke-agarose gels, an accurate determination of the spatial dose
      distribution is hindered by the diffusion of ferric ions. In this work, a model
      was developed to describe the diffusion process within gel samples of finite
      length and, thus, permit the reconstruction of the initial spatial distribution
      of the ferric ions. The temporal evolution of the ion concentration as a function
      of the initial concentration is derived by solving Fick's second law of diffusion
      in two dimensions with boundary reflections. The model was applied to magnetic
      resonance imaging data acquired at high spatial resolution (0.3 mm) and was found
      to describe accurately the observed diffusion effects.

PMID- 16644940
TI  - Defect complexes in Re3+-doped magnesium sulphate phosphors.
AB  - A series of magnesium sulphate phosphors MgSO4:RE3+,X ( RE = Dy, Tm, Eu and X =
      P, Mn) have been prepared and studied. Based on the experimental results of
      thermoluminescence (TL) emission spectra and dose responses studies, it is
      proposed that in these phosphors large defect complexes are formed, which include
      intrinsic imperfections and dopants. These defect complexes were formed in the
      course of preparation of phosphors and could be regarded as basic elements in the
      TL multi-stage processes. This defect model might be applicable to the most of TL
      materials.

PMID- 16644941
TI  - Development of a high range TLD dosemeter.
AB  - Global Dosimetry Solutions Inc. has developed a high range TLD dosemeter capable
      of measuring high-energy photon doses to 1 KGy. Additional correction factors
      have been established for as many as 10 various X ray and beta sources, allowing
      for high range monitoring of other sources and energies from 500 to 1000 Gy. The
      product utilizes TLD-100 and TLD-700 chips, available in three different
      configurations of very small size, and is offered at an economical price. Data
      analysis is quick, providing results within 24 h in most cases. This report
      describes the testing completed to support this product, primarily the
      determination of the supralinearity corrections necessary for doses up to 1 KGy.
      The test results are considered preliminary due to minimal data points between
      0.5 and 1.0 KGy. Additional irradiations are being conducted to establish a more
      accurate statistical curve at this high dose level. Due to the high dose residual
      these dosimeters are considered for single use only.

PMID- 16644942
TI  - Dose evaluation in lung-equivalent media in high-energy photon external
      radiotherapy.
AB  - In high-energy photon external radiotherapy treatment planning systems (TPSs) are
      used to calculate the dose to the target volume and the dose distribution around
      it. Commonly used TPSs include algorithms based on measurements in water and
      often fail in the estimate of dose in the presence of heterogeneities. In this
      study TL detectors were used to study the reliability of the Cadplan (Varian) TPS
      in the presence of low-density heterogeneities such as the lung for 6 and 18 MV
      photon beams at different field sizes. TL measurements were compared with TPS
      calculations and Monte Carlo simulations performed with the PENELOPE MC code. In
      a phantom with lung heterogeneity, TL measurements and MC simulations agreed,
      with an average deviation inside the lung of 2%. In contrast, TPS results
      overestimated the dose inside the lung, with a maximum deviation of 39% for the
      18 MV photon beam and a field size of 2 x 2 cm(2).

PMID- 16644943
TI  - Confocal fluorescent imaging of tracks from heavy charged particles utilising new
      Al2O3:C,Mg crystals.
AB  - A completely optical, non-destructive imaging of tracks in a fluorescent crystal
      provides a new way to detect and to assess doses from heavy charged particles and
      neutrons. The technique combines confocal fluorescent microscopy with a new
      radiation-sensitive, luminescent material based on aluminium oxide single
      crystals doped with carbon, magnesium and having aggregate oxygen vacancy defects
      (Al2O3:C,Mg). Radiation-induced colour centres in the new material have an
      absorption band at 620 nm and produce fluorescence at 750 nm with a high quantum
      yield and a short, 75 +/- 5 ns, fluorescence lifetime. Three-dimensional spatial
      distribution of fluorescent intensity allows one to obtain depth-dose
      distributions and to discriminate between high- and low-linear energy transfer
      radiations. Images of single tracks produced by different types of radiation have
      been obtained. Irradiations with a calibrated 241Am alpha source showed high
      efficiency for track detection. Thermal neutrons were detected using a nuclear
      reaction with a 6LiF radiator and production of alpha particles and tritium ions.
      Fast neutrons were detected using recoil protons produced in a polyethylene
      radiator installed in front of the crystalline detector. Three-dimensional
      reconstruction of a recoil proton propagating through the crystal was
      demonstrated.

PMID- 16644944
TI  - Performance of Harshaw TLD-100H two-element Dosemeter.
AB  - One of the advantages of LiF based thermoluminescent (TL) materials is its tissue
      equivalent property. The Harshaw TLD-100H (LiF:Mg,Cu,P) material has demonstrated
      that it has a near-flat photon energy response and high sensitivity. With the
      optimized dosemeter filters built into the holder, the Harshaw TLD-100H two
      element dosemeter can be used as a whole body personnel dosemeter for gamma, X
      ray and beta monitoring without the use of an algorithm or correction factor.
      This paper presents the dose performance of the Harshaw TLD-100H two-element
      dosemeter against the ANSI N13.11-2001 standard and the results of tests that are
      required in IEC 1066 International Standard.

PMID- 16644945
TI  - Experimental determination of the dose deposition profile of a 90Sr beta source.
AB  - Three different methods for characterising the dose deposition profile of a
      (90)Sr/(90)Y radioactive source are described: GAFChromic film dosimetry,
      Thermoluminescence (TL) and Optically Stimulated Luminescence (OSL). For the film
      measurements, GAFChromic film samples were stacked at different depths between
      polyethylene terephthalate (PET) foils. For TL, the thickness of a TLD-500
      dosemeter was gradually reduced by polishing and the TL from chips of different
      thickness was used in conjunction with a mathematical model based on the
      exponential attenuation of dose inside the crystal to determine the decay
      constant for the dose-depth profile. Finally, an OSL reader with confocal
      stimulation / detection capabilities was used to map the two-dimensional dose
      distribution in TLD-500 dosemeters as a function of depth. The shapes of the dose
      deposition profiles obtained from all the investigated methods are in good
      agreement.

PMID- 16644946
TI  - Measurements of the optical density and the thermoluminescent response of
      LiF:Mg,Ti exposed to high doses of 60Co gamma rays.
AB  - The absorption spectra and glow curves of LiF:Mg,Ti exposed to high doses of 60Co
      gamma rays as well as the optical density curves and thermoluminescent (TL)
      response as a function of dose were measured. Absorption peaks around 442 nm (2.8
      eV), 307 nm (4.0 eV) and 248 nm (5.0 eV) were observed. The optical density is a
      linear function of dose up to 2500 Gy and then sublinear for the 5.0 eV band, and
      for the 4.0 eV band it is sublinear with a filling constant of 2.1 x 10(-4) and
      6.2 x 10(-4) Gy(-1). The dose response of the 2.8 eV band is linear from 2500 Gy
      to 10 kGy with a slope of 1.0 x 10(-5) Gy(-1). Once the absorption spectra were
      obtained, the glow curves and the TL response were obtained. In the dose range,
      290-10,000 Gy, the TL response of peaks 5 and 7 was supralinear-sublinear.

PMID- 16644947
TI  - Radiation dosimetry for microbial experiments in the International Space Station
      using different etched track and luminescent detectors.
AB  - The laboratory of Microbiology at SCK.CEN, in collaboration with different
      universities, participates in several ESA programmes with bacterial experiments
      that are carried out in the International Space Station (ISS). The main objective
      of these programmes is to study the effects of space flight conditions such as
      microgravity and cosmic radiation on the general behaviour of model bacteria. To
      measure the radiation doses received by the bacteria, different detectors
      accompanied the microbiological experiments. The results obtained during two
      space flight missions are discussed. This dosimetry experiment was a
      collaboration between different institutes so that the doses could be estimated
      by different techniques. For measurement of the high linear energy transfer (LET)
      doses (>10 keV microm(-1)), two types of etched track detectors were used. The
      low LET part of the spectrum was measured by three types of thermoluminescent
      detectors ((7)LiF:Mg,Ti; (7)LiF:Mg,Cu,P; Al(2)O(3):C) and by the optically
      stimulated luminescence technique using Al(2)O(3):C detectors.

PMID- 16644948
TI  - Use of composites of topaz-glass as TSEE and TL dosemeters.
AB  - The properties of the thermally stimulated exoelectron emission (TSEE) and
      thermoluminescent (TL) emission of topaz-glass composites were studied with the
      aim of using them as solid-state dosemeters. The TSEE response was studied as a
      function of radiation energy and as a function of absorbed dose. Topaz-glass
      composites presented a linear TL and TSEE response to dose within a range of 0.01
      1 Gy. The topaz-glass composites presented higher TSEE peaks than topaz-Teflon
      pellets. In the dosimetry of radiotherapic fields normally the responses of the
      topaz-glass dosemeters are comparable to topaz-Teflon pellets. The results
      confirmed that these new dosemeters can be useful in monitoring the quality of
      the radiation sources. This dose mapping technique is particularly useful in
      investigating dose distribution throughout a planned target volume.

PMID- 16644949
TI  - Miniature semiconductor detectors for in vivo dosimetry.
AB  - Silicon mini-semiconductor detectors are found in wide applications for in vivo
      personal dosimetry and dosimetry and microdosimetry of different radiation
      oncology modalities. These applications are based on integral and spectroscopy
      modes of metal oxide semiconductor field effect transistor and silicon p-n
      junction detectors. The advantages and limitations of each are discussed.

PMID- 16644950
TI  - Optical absorption, TL and IRSL of basic plagioclase megacrysts from the pinacate
      (Sonora, Mexico) quaternary alkalic volcanics.
AB  - The paper presents the first results of an investigation on optical absorption
      (OA), thermally and infrared stimulated luminescence (TL and IRSL) of the
      Pinacate plagioclase (labradorite). The OA spectra reveal two bands with maxima
      at 1.0 and 3.2 eV connected with absorption of the Fe3+ and Fe2+ and IR
      absorption at wavelengths longer than 2700 nm. The ultraviolet absorption varies
      exponentially with the photon energy following the 'vitreous' empirical Urbach
      rule indicating exponential distribution of localised states in the forbidden
      band. The natural TL is peaked at 700 K. Laboratory beta irradiation creates a
      very broad TL peak with maximum at 430 K. The change of the 430 K TL peak shape
      under the thermal cleaning procedure and dark storage after irradiation reveals a
      monotonous increasing of the activation energy that can be explained by the
      exponential distribution of traps. The IRSL response is weak and exhibits a
      typical decay behaviour.

PMID- 16644951
TI  - Superlinear dose dependence of high temperature thermoluminescence peaks in
      Al2O3:C.
AB  - We report on strong superlinearity of high temperature (300-700 degrees C)
      thermoluminescence (TL) peaks in alpha-Al2O3:C powder. The main dosimetric peak
      at approximately 200 degrees C, previously found to exhibit slight
      superlinearity, is now shown to yield a slope of approximately 1.15 on a
      log(intensity) vs. log(dose) curve. Higher temperature peaks at approximately
      320, 450 and 650 degrees C, previously reported following UV and X-ray
      excitation, have now been observed after beta irradiation and showed stronger
      superlinearity. Using a blue filter, the weak peak at approximately 320 degrees C
      started about quadratically and the slope on the log-log scale decreased
      gradually from 2 to about unity at approximately 100 Gy. The two higher
      temperature peaks at approximately 450 and approximately 650 degrees C also
      exhibited a strong superlinear dose dependence in this dose range, with an
      average slope of approximately 2. Roughly similar behaviour has been found when a
      UV filter was used. The possible explanation of the strong superlinearity is
      discussed.

PMID- 16644952
TI  - Optically and thermally stimulated luminescence characteristics of MgO:Tb3+.
AB  - In this paper main optically stimulated luminescence (OSL) and thermoluminescence
      (TL) characteristics are presented of a newly synthesised material MgO doped with
      terbium (Tb) developed at the Institute of Nuclear Science, Vinca. A thermally
      stimulated emission spectrum showed the characteristic lines of Tb3+ in a wide
      range of wavelengths. The TL sensitivity of the main TL glow peak at 315 degrees
      C is 1.7 times higher than the TL of Al2O3:C. The highest OSL sensitivity was
      obtained under green lamp (500-570 nm) stimulation. The fast component in the OSL
      decay curve is 2.4 times faster than Al2O3:C. The OSL signal is linear with dose
      up to 10 Gy. The lower limit of detection was found to be 100 microGy. These
      first results show that the newly synthesised material has some promising
      properties for the application in radiation dosimetry.

PMID- 16644953
TI  - On the dose response of some CVD diamond thermoluminescent detectors.
AB  - The linearity of dose response of chemical vapour deposition (CVD) diamonds grown
      at the Institute for Materials Research at Limburg University, Belgium, was
      investigated over a dose range relevant for radiotherapy. The following CVD
      diamonds were investigated: (1) a batch of square 3 x 3 mm2 detectors cut from a
      CVD wafer and (2) an as-grown CVD wafer of 6 cm diameter. A total of 20 CVD
      square detectors were irradiated with 137Cs gamma rays over the dose range from
      200 mGy to 25 Gy. The CVD wafer, used as a large-area thermoluminescent (TL)
      detector, was exposed to a 226Ra needle. Very few square detectors showed
      linearity over a limited dose range, followed by saturation of the TL signal. The
      dose range of linearity was found to be strongly affected by the thermal
      annealing procedure of the detector. Owing to its high sensitivity and
      homogeneity of response, the large CVD diamond wafer was found to be very
      suitable as a large-area detector for 2-D dose mapping of the 226Ra brachytherapy
      source, possibly for Quality Assurance purposes.

PMID- 16644954
TI  - Monte Carlo simulation of the photon beam characteristics from medical linear
      accelerators.
AB  - The MCNPX code has been employed on a personal computer to calculate the
      dosimetric characteristics of the photon beams from the 6 MV Siemens MX2 and the
      10 MV Varian Clinac 2100C linear accelerators. A model of the treatment head
      includes the major geometric structure within the beam path. The model was used
      to calculate the energy spectra of the photon beam, percentage depth dose and the
      dose profiles. The accuracy of the calculated results is examined by comparing
      them with the measured dose distributions for the two machines. The computed and
      measured depth dose curves agree to within 2% for all the depths beyond the build
      up region for both treatment machines. The calculations agree to within 2% of the
      measured profiles within the 100-50% dose level. It has been found that the MCNPX
      code is an effective tool for simulating the clinical photon beam.

PMID- 16644955
TI  - Neutron detection and dosimetry using polycrystalline CVD diamond detectors with
      high collection efficiency.
AB  - Polycrystalline chemical vapour deposited (CVD) diamond film is an interesting
      material for neutron detection and dosimetry. However, the use of CVD diamond
      detectors is still limited by the low-level signal pulse produced because of the
      high energy required to produce an electron-hole pair in diamond (13.2 eV) and by
      the reduced charge collection efficiency owing to several types of traps for
      electrons and holes in CVD films. A new type of CVD diamond detector with high
      gain (HG) contacts was produced as part of the collaboration between the ENEA
      Fusion Division and the Faculty of Engineering of Rome 'Tor Vergata' University.
      In this paper the performance of the HG CVD diamond detector is presented and
      possible applications of CVD diamond detectors to neutron dosimetry are also
      discussed.

PMID- 16644956
TI  - Use of commercial alanine and TL dosemeters for dosimetry intercomparisons among
      Italian radiotherapy centres.
AB  - In the implementation of a large-scale dosimetry intercomparison one of the main
      constraints is the availability of large number of dosemeters of the highest
      quality. Therefore, ISS tested the possibility of using commercially available
      dosemeters, alanine pellets and thermoluminescence (TL) dosimetry chips, for
      transfer dosimetry within the Italian intercomparison programme. In this work the
      characterisation of commercial alanine and TL dosemeters along with the ISS dose
      assessment procedure used in the Italian intercomparison are reported. Results
      demonstrate the feasibility of the ISS approach to transfer dosimetry since it is
      possible to measure 10 Gy with a combined uncertainty of 1% (1sigma) and 1 Gy
      with a combined uncertainty of 1.7% (1sigma) with alanine and TL dosemeters,
      respectively.

PMID- 16644957
TI  - Electron dose radiation response of dyed PMMA detectors developed at IPEN.
AB  - Dyed polymethylmethacrylate (PMMA) detectors using yellow, red, blue and green
      colouring compounds, commercially available in Brazil, were originally developed
      and characterised using the optical absorption (OA) technique for gamma
      radiation, with the aim of obtaining a sensitive, useful, practical and cheap
      dosemeter for use in the quality control of industrial gamma radiation
      processing. In this work these detectors were evaluated for electron OA response,
      for use in the quality control of electron accelerator radiation processing. The
      studied parameters were the absorption spectra, dose-rate dependence between 2.66
      and 45.22 kGy s(-1); dose response between 1.2 and 110 kGy; and energy dependence
      of response between 0.8 and 1.5 MeV electron energy.

PMID- 16644958
TI  - Calibration of a TLD-100 powder dosimetric system to verify the absorbed dose to
      water imparted by 137Cs sources in low dose rate brachytherapy at the oncology
      unit in the Hospital General de Mexico.
AB  - A thermoluminescence dosimetry (TLD) system was characterised at SSDL-ININ to
      verify the air-kerma strength (S(K)) and dose-to-water (D(W)) values for (137)Cs
      sources used in low dose rate (LDR) brachytherapy treatments at the Hospital
      General de Mexico (HGM). It consists of a Harshaw 3500 reader and a set of TLD
      100 powder capsules. The samples of TLD-100 powder were calibrated in terms of
      D(W) vs. nC or nC mg(-1), and their dose response curves were corrected for
      supralinearity. The D(W) was calculated using the AAPM TG-43 formalism using S(K)
      for a CDCSM4 (137)Cs reference source. The S(K) value was obtained by using a NE
      2611 chamber, and with two well chambers. The angular anisotropy factor was
      measured with the NE 2611 chamber for this source. The HGM irradiated TLD-100
      powder capsules to a reference dose D(W) of 2 Gy with their (137)Cs sources. The
      percent deviations between the imparted and reference doses were 1.2% < or =
      Delta < or = 6.5%, which are consistent with the combined uncertainties: 5.6% <
      or = u(c) < or = 9.8% for D(W).

PMID- 16644959
TI  - Photon and fast neutron dosimetry using aluminium oxide thermoluminescence
      dosemeters.
AB  - Al(2)O(3):Mg,Y thermoluminescence (TL) dosemeters were used to measure photon and
      fast neutron doses in a fast neutron beam recently implemented at the Portuguese
      Research Reactor, Nuclear and Technological Institute, Portugal. The activation
      of Al(2)O(3):Mg,Y by fast neutrons provides information about the fast neutron
      component by measuring the activity of the reaction products and the self-induced
      TL signal. Additionally, the first TL reading after irradiation determines the
      photon dose. The elemental composition of the dosemeters was determined by
      instrumental neutron activation analysis and by particle induced X-ray emission.
      Results demonstrate that Al(2)O(3):Mg,Y is an adequate material to discriminate
      photon and fast neutron fields for reactor dosimetry purposes.

PMID- 16644960
TI  - Energy responses of the LiF series TL pellets to high-energy photons in the
      energy range from 1.25 to 21 MV.
AB  - The energy responses for the KLT-300(LiF:Mg,Cu,Na,Si, Korea), GR-200(LiF:Mg,Cu,P,
      China) and MCP-N(LiF:Mg,Cu,P, Poland) thermoluminescence(TL) pellets were studied
      for a photon radiation with energies from 1.25 MeV(60Co) to 21 MV (Microtron) to
      verify the usefulness of the calibration for the radiotherapy beams. The
      International Atomic Energy Agency (IAEA) and the World Health Organization (WHO)
      have performed thermoluminescence dosimetry (TLD) audits to verify the
      calibration of the beams by TL powder, but TL pellets were used in this study
      because the element correction factor (ECF), defined as the factor to correct the
      variations that all TL dosemeters cannot be manufactured to have exactly the same
      TL efficiency, for each TL pellet could be accurately derived and be handled
      conveniently when compared with the powder. Also several works for the energy
      response of the TLDs were done for the low-energy photon beams up to 60Co, but
      they will be extended in this experiment to the high photon energies (up to 20
      MV), which are widely used in the therapy level of a radiation. The PTW 30006
      ionisation chamber was calibrated by the Korea primary standards to establish the
      air-kerma rates and the TL pellets were irradiated in a specially designed
      waterproof pellet holder in a water phantom (30 x 30 x 30 cm3) just like the IAEA
      postal audits programme. This result was compared with that of another type of
      phantom [10 (W) x 10 (L) x 10 (H) cm3 PMMA Perspex phantom for the 60Co and 6 MV
      photon, and 10 x 10 x 20 (H) cm3 for the 10 and 21 MV photon] for its convenient
      use and easy handling and installation in a hospital. The results show that the
      differences of the responses for the water phantom and PMMA Perspex phantom were
      negligible, which is contrary to the general conception that a big difference
      would be expected. For an application of these results to verify the therapy
      beams, an appropriate energy correction factor should be applied to the energies
      and phantom types in use.

PMID- 16644961
TI  - Direct dark matter search using large-mass superheated droplet detectors in the
      PICASSO experiment.
AB  - The PICASSO experiment investigates the presence and nature of dark matter in the
      Universe. The experiment is based on the detection of acoustic signals generated
      in explosive phase transitions induced by dark matter particles. This technique
      is an alternative more traditional detection technique like scintillation and
      ionisation, which are largely employed for dark matter search. One of the main
      advantages of this technique, besides its sensitivity to very low nuclear recoil
      energies (few keV), is its excellent background suppression features. A pilot
      experiment consisting of six superheated droplet detectors (40 g of active mass)
      is presently taking data at the Sudbury Neutrino Observatory (SNO) at a depth of
      2000 m. We discuss the operation, calibration and data acquisition of the
      experiment and also the ongoing work to increase the sensitivity and the active
      mass of the detectors.

PMID- 16644962
TI  - Dose evaluation in paediatric radiology and adult bone densitometry examinations.
AB  - Dose measurements are acknowledged to be a vital part of the quality assurance
      process in diagnostic radiology, and the use of thermoluminescence dosemeters
      (TLDs) is a recommended method of entrance dose evaluation. Measurement of doses
      in radiographic examinations is widely adopted in clinical practice for adults as
      well as for children. Phantoms can be used to simulate different parts of the
      body, depending on the materials used to build them. In this work two different
      sets of phantoms have been prepared with acrylic blocks. The first set was used
      to simulate children of different ages. The second set was used to simulate the
      adult spine. The dosimetric measurements have been carried out using TLD and an
      ionising chamber. Measurements were performed in three X-ray equipments in
      Aracaju, Brazil. The entrance, half thickness and exit surface doses were
      analysed.

PMID- 16644963
TI  - On measuring the output of an IORT mobile dedicated accelerator.
AB  - In the present work, dose-to-water values derived from Fricke (operated by the
      Italian Primary Standard Dosimetry Laboratory) and alanine (operated by the
      Istituto Superiore di Sanita, Italy) measurements in IORT electron beams
      characterised by a high dose per pulse were compared to show the extent of
      equivalence of the two dosimetry systems. This study demonstrates agreement
      (within 2%) of the two dosimetry systems for plane-base IORT applicators, but in
      the case of small diameter (40 mm) and bevelled (22.5 degrees ) applicators,
      Fricke dosemeters underestimated doses by 2.4%. For base bevelled IORT
      applicators (22.5 degrees or more) with small diameter ( approximately 40 mm or
      less) reduced dimensions of the dosemeter are needed. Under these measurement
      conditions, the alanine dosemeter gives better accuracy in beam output
      determination compared with the Fricke dosemeter used.

PMID- 16644964
TI  - Monte Carlo simulation of a medical linear accelerator for radiotherapy use.
AB  - A Monte Carlo code MCNPX (Monte Carlo N-particle) was used to model a 25 MV
      photon beam from a PRIMUS (KD2-Siemens) medical linear electron accelerator at
      the Centre Antoine Lacassagne in Nice. The entire geometry including the
      accelerator head and the water phantom was simulated to calculate the dose
      profile and the relative depth-dose distribution. The measurements were done
      using an ionisation chamber in water for different square field ranges. The first
      results show that the mean electron beam energy is not 19 MeV as mentioned by
      Siemens. The adjustment between the Monte Carlo calculated and measured data is
      obtained when the mean electron beam energy is approximately 15 MeV. These
      encouraging results will permit to check calculation data given by the treatment
      planning system, especially for small fields in high gradient heterogeneous
      zones, typical for intensity modulated radiation therapy technique.

PMID- 16644965
TI  - Method of Monte Carlo simulation verification in hadron therapy with non-tissue
      equivalent detectors.
AB  - In hadron therapy the spectra of secondary particles can be very broad in type
      and energy. The most accurate calculations of tissue equivalent (TE) absorbed
      dose and biological effect can be achieved using Monte Carlo (MC) simulations
      followed by the application of an appropriate radiobiological model. The
      verification of MC simulations is therefore an important quality assurance (QA)
      issue in dose planning. We propose a method of verification for MC dose
      calculations based on measurements of either the integral absorbed dose or the
      spectra of deposited energies from single secondary particles in non-TE material
      detectors embedded in a target of interest (phantom). This method was tested in
      boron neutron capture therapy and fast neutron therapy beams.

PMID- 16644966
TI  - Properties of the 4.45 eV optical absorption band in LiF:Mg,Ti.
AB  - The optical absorption (OA) and thermoluminescence (TL) of dosimetric LiF:Mg,Ti
      (TLD-100) as well as nominally pure LiF single crystal have been studied as a
      function of irradiation dose, thermal and optical bleaching in order to
      investigate the role of the 4.45 eV OA band in low temperature TL. Computerised
      deconvolution was used to resolve the absorption spectrum into individual
      gaussian bands and the TL glow curve into glow peaks. Although the 4.45 eV OA
      band shows thermal decay characteristics similar to the 4.0 eV band its dose
      filling constant and optical bleaching properties suggest that it cannot be
      associated with the TL of composite peaks 4 or 5. Its presence in optical grade
      single crystal LiF further suggests that it is an intrinsic defect or possibly
      associated with chance impurities other than Mg, Ti.

PMID- 16644967
TI  - Search for ionisation density effects in the radiation absorption stage in
      LiF:Mg,Ti.
AB  - Optical absorption (OA) dose-response of LiF:Mg,Ti (TLD-100) is studied as a
      function of electron energy (ionisation density) and irradiation dose. Contrary
      to the situation in thermoluminescence dose-response where the supralinearity is
      strongly energy-dependent, no dependence of the OA dose filling constants on
      energy is observed. This result is interpreted as indicating a lack of
      competitive process in the radiation absorption stage. The lack of an energy
      dependence of the dose filling constant also suggests that the charge carrier
      migration distances are sufficiently large to smear out the differences in the
      non-uniform distribution of ionisation events created by the impinging
      gamma/electron radiation of various energies.

PMID- 16644968
TI  - On the relationship between dose-, energy- and LET-response of thermoluminescent
      detectors.
AB  - Measurements of the response of thermoluminescent (TL) detectors after gamma ray
      doses high enough to observe signal saturation provide input to microdosimetric
      models which relate this gamma-ray response with the energy response after low
      doses of photons (gamma rays and low-energy X rays) and after high-LET
      irradiation. To measure their gamma ray response up to saturation, LiF:Mg,Ti (MTS
      7 and MTT), LiF:Mg,Cu,P (MCP-7), CaSO4:Dy (KCD) and Al2O3:C detectors were
      irradiated with 60Co gamma rays over the range 1-5000 Gy. The X-ray photon energy
      response and TL efficiency (relative to gamma rays) after doses of beta rays and
      alpha particles, were also measured, for CaSO4:Dy and for Al2O3:C.
      Microdosimetric and track structure modelling was then applied to the
      experimental data. In a manner similar to LiF:Mg,Cu,P, the experimentally
      observed under response of alpha-Al2O3:C to X rays <100 keV, compared with cross
      section calculations, is explained as a microdosimetric effect caused by the
      saturation of response of this detector without prior supralinearity (saturation
      of traps along the tracks). The enhanced X-ray photon energy response of CaSO4:Dy
      is related to the supralinearity observed in this material after high gamma ray
      doses, similarly to that in LiF:Mg,Ti. The discussed model approaches support the
      general rule relating dose-, energy- and ionisation density-responses in TL
      detectors: if their gamma ray response is sublinear prior to saturation, the
      measured photon energy response is lower, and if it is supralinear, it may be
      higher than that expected from the calculation of the interaction cross sections
      alone. Since similar rules have been found to apply to other solid-state detector
      systems, microdosimetry may offer a valuable contribution to solid-state
      dosimetry even prior to mechanistic explanations of physical phenomena in
      different TL detectors.

PMID- 16644969
TI  - Influence of absorbed dose and deep traps on thermoluminescence response: a
      numerical simulation.
AB  - Numerical simulations based on standard rate equations are carried out to study
      the dependence of the thermoluminescence (TL) response on the absorbed dose. The
      model, which includes thermally stimulated exoelectronic emission (TSEE), uses
      three electron traps--two active and one thermally disconnected (TD)--and one
      deep hole trap acting as a recombination centre. After instantaneous creation of
      a given dose of electron-hole pairs, one first follows isothermal recombination
      and trap filling before simulating the TL readout. Influence of TD traps and
      specific effects due to trap saturation are illustrated. A systematic study of
      the TL response is performed in wide ranges of the determining parameters. The
      dose dependence is found to be quadratic, linear or intermediate according to
      their relative values. Results are explained in terms of recombination-trapping
      competition, trap occupancy and in relation with the presence of TSEE.

PMID- 16644970
TI  - Correlation between thermoluminescence and mechanoluminescence of gamma
      irradiated Dy activated potassium and magnesium mixed sulphate.
AB  - Thermoluminescene (TL) and mechanoluminescence (ML) properties of gamma
      irradiated Dy activated potassium and magnesium mixed sulphate have been studied.
      (K2Mg2:Dy) (SO4)3 samples having different concentrations of Dy were prepared by
      solid-state diffusion method. Two distinct peaks, the first approximately 130
      degrees C and the second approximately 273 degrees C, are observed in the TL glow
      curve. It is also observed that TL intensities of both peaks decrease when TL
      glow curves were recorded after deforming the irradiated samples. Only one peak
      is observed in the ML intensity vs. time curve and the ML intensity decreases
      markedly with the post-irradiation annealing (to remove 130 degrees C TL peak) of
      the sample. Both ML and TL intensities have been observed optimum for 1 mol% of
      Dy in the mixed sulphate system. It is suggested that the recombination of
      electrons with the free radicals (anion radicals produced by gamma irradiation)
      released from the traps during the thermal or mechanical excitation is
      responsible for luminescence in this system.

PMID- 16644971
TI  - A real-time, high-resolution optical fibre dosemeter based on optically
      stimulated luminescence (OSL) of KBr:Eu, for potential use during the
      radiotherapy of cancer.
AB  - A real-time optically stimulated luminescence (OSL) dosimetry system for
      potential in vivo use during radiotherapy treatments is proposed. Single-crystal
      europium-doped KBr samples were grown in a Bridgman furnace, and characterised
      using optical absorption techniques. An algorithm for the processing of the OSL
      signal was defined for use in real-time measurements, and its performance was
      studied on data obtained with a home-built reader, using optical-fibre-coupled
      dosemeters. OSL dose-response, fading properties and temperature dependence of
      the signal were investigated in correlation with the concentration of Eu(2+)
      dopant in the sample.

PMID- 16644972
TI  - Thermoluminescence emission spectra for the LiF:Mg,Cu,Na,Si thermoluminescent
      materials with various concentrations of the dopants (3-D measurement).
AB  - The thermoluminescence (TL) emission spectra from LiF TL materials, called KLT
      300 (LiF:Mg,Cu,Na,Si) with various dopant concentrations are measured and
      analysed. These KLT-300 materials were developed by the Korea Atomic Energy
      Research Institute (KAERI) to achieve an enhancement of the thermal stability in
      TL readings. Six types of samples are prepared with different dopant
      concentrations in the following ranges; Mg (0-0.20 mol%), Cu (0-0.05 mol%), Na
      and Si (0-0.9 mol%). The spectra measurements are carried out for the six types
      of samples using a TL emission spectra measurement device. The spectra
      measurement device consists of a monochromator, photomultiplier tube and
      temperature control unit to thermally stimulate the samples. The measured data
      shows the light emission during heating of the sample as a function of
      temperature and wavelength (three-dimensional TL spectra). The spectra were
      analysed using a method of deconvolution based on gaussian curve. The wavelength
      of a main peak of the emission spectra changes depending on the existence of the
      Cu dopant, while intensity of the spectra rapidly changes with the Cu dopant
      concentrations. The 385 nm emission is mainly observed in all the spectra from
      the samples with the Cu dopant, but in those from the samples without the Cu
      dopant a very weak 401 nm emission is mainly observed. However, any change in the
      wavelength at a main peak of the TL emission spectra from the sample materials
      with Na and Si dopants is not observed but that in the intensity at a peak of the
      spectra is observed.

PMID- 16644973
TI  - An algorithm for real-time dosimetry in intensity-modulated radiation therapy
      using the radioluminescence signal from Al2O3:C.
AB  - Although the radioluminescence (RL) signal from optical fibre Al(2)O(3):C
      dosemeters used in medical applications is essentially proportional to dose rate,
      the crystals used so far are imperfect in the sense that their RL sensitivity
      changes with accumulated dose. A computational algorithm has been developed that
      corrects for these sensitivity changes. We further report on a new system that
      effectively separates the RL signal generated in the crystal from fluorescence
      and Cerenkov emission generated in the optical fibre cable using a gating
      technique in connection with pulsed linear accelerator radiation beams. The
      dosimetry system has been used for dose measurements in a phantom during an
      intensity-modulated radiation therapy (IMRT) treatment with 6 MV photons. The RL
      measurement results are in excellent agreement (i.e. within 1%) with both the OSL
      results and the dose delivered according to the treatment planning system. RL
      signals from Al(2)O(3):C can be used for real-time dose rate measurements with a
      time resolution of approximately 0.1 s and a spatial resolution only limited by
      the size of the detector (<0.5 mm).

PMID- 16644974
TI  - Non-monotonic dose dependence of thermoluminescence.
AB  - The thermoluminescence (TL) intensity in different materials is usually a
      monotonic increasing function of the dose, which quite often reaches a saturation
      value. In several materials, however, non-monotonic dose dependence has been
      observed. The TL intensity reached a maximum at a certain dose and decreased at
      higher ones. Some authors refer to this effect as 'radiation damage'. In the
      present work, we show that the non-monotonic dependence can easily be
      demonstrated to result from competition between transitions model with two
      trapping states and two kinds of recombination centres. Two kinds of competition
      are considered. One in which competition during excitation dominates, the filling
      of the active luminescence centre is non-monotonic, and the resulting TL is non
      monotonic. In the other, the filling of traps and centres is monotonically
      increasing, but the competition during heating causes TL intensity to reach a
      maximum and decline at higher doses.

PMID- 16644975
TI  - A method for measuring tissue-equivalent dose using a pin diode and activation
      foil in epithermal neutron beams with EN < 100 keV.
AB  - Silicon (Si) pin diodes can be used for neutron dosimetry by observing the change
      in forward bias voltage caused by neutron induced displacement damage in the
      diode junction. Pin diode energy response depends on Si displacement damage KERMA
      (K(Si)). It is hypothesised that tissue-equivalent (TE) neutron dose could be
      expressed as a linear combination of K(Si) and foil activation terms. Monte Carlo
      simulations (MCNP) of parallel monoenergetic neutron beams incident on a
      cylindrical TE phantom were used to calculate TE dose, K(Si) and Au, Cu and Mn
      foil activations along the central axis of the phantom. For spectra with neutron
      energies <100 keV, it is possible to estimate the TE kerma based on silicon
      damage kerma and Cu or Mn foil measurements. More accurate estimates are possible
      for spectra where the maximum neutron energy does not exceed 30 keV.

PMID- 16644976
TI  - Application of different TL detectors for the photon dosimetry in mixed radiation
      fields used for BNCT.
AB  - Different approaches for the measurement of a relatively small gamma dose in
      strong fields of thermal and epithermal neutrons as used for Boron Neutron
      Capture Therapy (BNCT) have been studied with various thermoluminescence
      detectors (TLDs). CaF(2):Tm detectors are insensitive to thermal neutrons but not
      tissue-equivalent. A disadvantage of applying tissue-equivalent (7)LiF detectors
      is a strong neutron signal resulting from the unavoidable presence of (6)Li
      traces. To overcome this problem it is usual to apply pairs of LiF detectors with
      different (6)Li content. The experimental determination of the thermal neutron
      response ratio of such a pair at the Geesthacht Neutron Facility (GeNF) operated
      by PTB enables measurement of the photon dose. In the experimental mixed field of
      thermal neutrons and photons of the TRIGA reactor at Mainz the photon dose
      measured with different types of (7)LiF/(nat)LiF TLD pairs agree within a
      standard uncertainty of 6% whereas the CaF(2):Tm detectors exhibit a photon dose
      by more than a factor of 2 higher. It is proposed to determine suitable photon
      energy correction factors for CaF(2):Tm detectors with the help of the
      (7)LiF/(nat)LiF TLD pairs in the radiation field of interest.

PMID- 16644977
TI  - Ferrous-Ferric Ion exchange dosemeter.
AB  - In this work a three-dimensional ferrous-ferric ion exchange dosemeter is
      proposed and the dose response measured. The dosemeter consists of strong acid
      cation exchange resin beads in the H form in water. Amberlyst 15 Wet beads with a
      harmonic mean diameter of 0.600-0.850 mm were prepared by soaking them in an
      aqueous solution of ferrous ammonium sulphate to exchange ferrous ions for H(+)
      ions. The beads were rinsed with distilled water and packed in glass vials. Sets
      of samples with ferrous ion concentrations of 0.5 and 1.0 mM were dosed with 6 MV
      X rays from a Varian 2100C linac. The spin-lattice relaxation time constants (T1)
      for the samples were measured using an Apollo spectrometer (Tecmag, Houston, TX)
      interfaced to a 1.5 T magnet (Magnex, Abingdon, UK). Each sample had two T1
      values; a long T1 at 1200 ms that did not significantly change with dose and a
      short T1 that ranged from 56 ms at 0 Gy to 36 ms at 100 Gy. The R1 vs. dose
      responses were linear with slopes of 0.066 and 0.079 s(-1) Gy(-1).

PMID- 16644978
TI  - Theoretical and experimental investigation of the f(D)max-(S/S0)max anomaly in
      LiF:Mg,Ti.
AB  - Previous investigations in the framework of the Unified Interaction Model (UNIM)
      have demonstrated the difficulty in theoretically predicting both f(D)max and
      [S(Ds)/S(0)]max with the same set of UNIM parameters. This anomaly is re
      investigated and an alternative explanation, based on experimental measurements
      combined with UNIM analysis, is given. This explanation is based on the
      assumption that N(LC), the total number of available luminescent centres is
      changed by the sensitisation dose or anneal or both. Allowing N(LC) to increase
      as the sensitisation dose is increased, a good fit to both f(D) and S(Ds)/S0 is
      obtained.

PMID- 16644979
TI  - Application of TL as a geochemical sensor.
AB  - Two-dimensional thermoluminescence (TL) and spectroscopy of rock samples were
      measured to identify a mass transport front in rock matrix. Samples were selected
      from the Kamaishi Mine including the hydrothermal mineral veins and the
      surrounding altered zone. Results showed some different distribution of TL
      intensity between the altered and unaltered zones. Minerals in the altered zone
      showed stronger TL than those in the unaltered zone, and different phenomena for
      wavelength could be observed between them. Therefore, it could possibly be shown
      that TL can be used as a chemical sensor, which identifies mass change (transport
      front in rocks), by using these TL methods.

PMID- 16644980
TI  - Comparison of two extremity dosemeters based on LiF:Mg,Cu,P thin detectors for
      mixed beta-gamma fields.
AB  - Two types of thin LiF:Mg,Cu,P detectors, GR-200F and MCP-Ns, have been
      characterised for use in the design of an extremity dosemeter for mixed beta
      photon radiation fields. Both detectors consist of an extremely thin layer of
      sensitive material with effective thicknesses of 5 and 8 mg cm(-2), respectively,
      held in a 5 mg cm(-2) PVC ring holder. Dosimetric performance was analysed
      according to the ISO 12794 standard and compared with 240 mg cm(-2) TLD-100
      measurements. In particular, the energy response was obtained for ISO narrow X
      ray spectra, (137)Cs, (60)Co, (204)Tl and (90)Sr/(90)Y. From these measurements a
      mean calibration factor was calculated to estimate H(p)(0.07). Subsequently, the
      performance of the dosemeters was checked for a set of 10 different mixed photon
      and beta-photon fields. The study shows that the proposed dosemeters can estimate
      H(p)(0.07) in a wide range of mixed beta-photon fields with a maximum deviation
      from the given dose of 30% and an overall uncertainty of the order of 25% (k =
      1). However, the results also highlight a large variability among the different
      thin detectors and, thus, the standard TLD-100 material is recommended whenever
      the workplace does not include low-energy beta radiation.

PMID- 16644981
TI  - Time-resolved spectroscopy of LiF:Mg,Cu,P.
AB  - Time-resolved spectroscopy measurements of LiF:Mg,Cu,P luminescence are presented
      to obtain a better understanding of the emission characteristics of this
      material. The intensities and decay of the emission bands were studied as a
      function of annealing temperature and ionising radiation (gamma) dose. Two peaks
      in the emission were observed at 367 and 466 nm when excited by the 266 nm laser
      radiation. The luminescence spectrum under band-to-band X-ray excitation shows a
      dominant emission approximately 390-400 nm, which resembles the reported
      thermoluminescence emission and is clearly different from the spectrum obtained
      using the 266 nm pulsed laser excitation. Annealing of the material to 300
      degrees C increases the intensity of the 367 and 466 nm emission bands by an
      order of magnitude as well as changes the relative intensity of the bands.
      Additional emission bands, which are not evident in the thermoluminescence
      emission spectra, are seen at longer wavelengths that also increase with dose.
      Possible explanations for the observed emission spectra are discussed in this
      paper.

PMID- 16644982
TI  - Thermoluminescence glow curves and optical stimulated luminescence of undoped
      alpha-Al2O3 crystals.
AB  - The characteristics of thermoluminescence (TL) and optical stimulated
      luminescence (OSL) in undoped alpha-Al2O3 single crystals were studied. The TL
      glow curves of the crystal samples irradiated at various dose levels were
      measured by RisO TL/OSL-DA-15B/C reader with U-340 or 7-59 filters at different
      heating rates. The glow peaks measured with U-340 at approximately 210 degrees C
      of the undoped alpha-Al2O3 can be well fitted by first-order kinetic equation
      whereas the glow peaks measured with 7-59 filters are a composite of two first
      order glow peaks. It indicates that the TL glow curves are dependent upon the
      filter used in the reader that is related to the emission spectra of luminescence
      materials. The OSL were also measured and fitted by two exponential functions to
      get the luminescence intensities. The TL and OSL dose responses of the undoped
      alpha-Al2O3 crystal were obtained in the dose range of 0.12-248 Gy and fitted by
      the composite action dose-response function to get nonlinear characteristic
      parameters. The TL and OSL dose responses are linear-sublinear.

PMID- 16644983
TI  - TL and OSL of SrSO4 phosphors doped with Eu.
AB  - The thermoluminescence (TL) and optically stimulated luminescence (OSL) of
      SrSO4:Eu (0.1 mol%) powder sample were studied. The TL and OSL emission spectrum
      are measured after irradiation (absorbed dose 100 Gy) of 90Sr source; both of
      them showed that the emission wavelength is at approximately 375 nm, which
      indicates that TL and OSL have the same luminescence centres, and the
      luminescence comes from transitions between the energy levels of Eu2+. The TL
      glow curves and OSL decay curves illustrate that there is only one main TL peak
      but two main components in OSL curves. By a comparative study of TL and OSL it is
      concluded that OSL traps are different from TL traps. The TL and OSL dose
      responses of SrSO4:Eu phosphor were measured, and it showed that phosphor has
      similar dose responses for OSL and TL.

PMID- 16644984
TI  - Thermoluminescence behaviour of KCL(1-x)Br(x):Pb2+ exposed to gamma radiation.
AB  - The thermoluminescence (TL) behaviour of solid solutions of lead doped KCl(1
      x)Br(x) (X = 0.02, 0.35, 0.50, 0.65, 0.85, 1) mixed crystals exposed to gamma
      radiation at different doses from 60Co is reported. The TL glow curves of KCl(1
      x)Br(x):Pb2+ crystal exposed in the range of 0-140 Gy is strongly dependent on
      composition X. The maximum temperature of the main TL glow peak was found to
      shift towards lower temperatures as composition X increased and a significant
      enhancement of the TL efficiency in KCl(1-x)Br(x):Pb2+ was found for X = 0.50
      which is attributed to an increase in the vacancy concentration of the mixed
      halides at middle composition. The participation of the F-centre in the TL
      phenomenon particularly related to the main TL glow peak observed in mixed
      samples was also confirmed.

PMID- 16644985
TI  - The use of optically stimulated luminescence from AL2O3:C in the dosimetry of
      high-energy heavy charged particle fields.
AB  - This paper presents two different approaches of quantifying the optically
      stimulated luminescence (OSL) response of Al(2)O(3):C to high-energy heavy
      charged particles (HCPs). The OSL efficiency of Al(2)O(3):C exposed to different
      HCPs is defined as the sensitivity of the material to HCPs normalised by the
      sensitivity to gamma. In this paper, we investigate the possibility of
      introducing a 'mean efficiency' eta(mean), which when used in conjunction with
      the total gamma dose D(gamma) measured for a mixed radiation exposure allows for
      the determination of the absorbed dose without the need to determine the
      individual contributions of different types of radiation to the OSL signal. We
      tested the hypothesis that information regarding the 'mean efficiency' eta(mean)
      is contained in the shape of the OSL decay curve, using several approaches in the
      analysis of the OSL data. This analysis was applied to various mixed field
      irradiations performed at the HIMAC facility, Chiba, Japan. The results of this
      analysis are discussed.

PMID- 16644986
TI  - Defect analysis in natural quartz from Brazilian sites for ionising radiation
      dosimetry.
AB  - The impurity-related point defects and the dosimetry properties of quartz
      irradiated with gamma- and X-rays doses were investigated for natural crystals
      taken from different geologies. The specimens were initially irradiated with
      gamma particles from (137)Cs to determine the sensitivity and repeatability of
      thermoluminescence (TL) emission at approximately 503 K. The dose response was
      investigated in the range 1-20 mGy. The energy dependence was considered in the
      range 16-65 keV with X rays and with gamma rays from 137Cs and 60Co. It was found
      that quartz material from two geologies exhibit a linear relationship between TL
      intensities and absorbed doses with high angular coefficients. Its sensitivities
      are higher than that found for LiF TLD-100 dosemeters irradiated in the same
      conditions. The results were discussed in relation to pre-existing impurity
      contents and the formation of Al-hole centres.

PMID- 16644987
TI  - The ENEA neutron personal dosimetry service.
AB  - The ENEA Radiation Protection Institute has been operating the only neutron
      personal dosimetry service in Italy since the 1970s. Since the 1980s the service
      has been based on PADC (poly allyl diglycol carbonate) for fast neutron
      dosimetry, while thermal neutron dosimetry has been performed using
      thermoluminescence (TL) dosemeters. Since the service was started, a number of
      aspects have undergone evolution. The latest and most important changes are as
      follows: in 1998 a new PADC material was introduced in routine, since 2001 TL
      thermal dosimetry has been based on LiF(Mg,Cu,P) [GR-200] and (7)LiF(Mg,Cu,P) [GR
      207] detectors and since 2003 a new image analysis reading system for the fast
      neutron dosemeters has been used. Herein an updated summary of how the service
      operates and performs today is presented. The approaches to calibration and
      traceability to estimate the quantity of H(p)(10) are mentioned. Results obtained
      at the performance test of dosimetric services in the EU member states and
      Switzerland sponsored by the European Commission and organised by Eurados in 1999
      are reported. Last but not least, quality assurance (QA) procedures introduced in
      the routine operation to track the whole process of dose evaluation (i.e. plastic
      QA, acceptance test, test etching bath reproducibility and 'dummy customer'
      (blind test) for each issuing monitoring period) are presented and discussed.

PMID- 16644988
TI  - The implementation in routine of the ENEA new personal photon dosemeter.
AB  - The ENEA photon dosemeter, introduced in 1995, consisting of two differently
      filtrated LiF(Mg,Cu,P) detectors, has been modified recently. The ABS
      (acrylonitrile butadiene styrene) plastic support has been replaced by a new
      aluminium card supporting the same two detectors (LiF(Mg,Cu,P) GR200). The new
      card, fully developed at the ENEA-Radiation Protection Institute (which is going
      to be patented), can now be processed through a Harshaw Model 6600 Automated TLD
      Reader, a hot gas reader. This paper reports the results of the individual
      calibration of approximately 60,000 LiF(Mg,Cu,P) GR200 detectors inserted on the
      new aluminium cards. Before the implementation in routine of the new cards, the
      reader has been characterised. Steps and tests to be made to use the card in
      routine (i.e. reader stability, linearity, reproducibility, etc.) are reported.
      The whole dosimetric system now combines the very good performances of the
      Harshaw Model 6600 reader and that of LiF(Mg,Cu,P) thermoluminescent material.

PMID- 16644989
TI  - Radiation damage induced by krypton ions in sintered alpha-Al2O3.
AB  - Alpha-alumina is a useful thermoluminescence (TL) dosemeter. The knowledge of its
      behaviour under irradiation is thus of primary importance. The purpose of this
      paper is to characterise the radiation damage produced by swift krypton ions
      using various experimental methods, namely TL, optical absorption, fluorescence
      and electron paramagnetic resonance (EPR). After ion irradiation, the TL
      intensity is shown to decrease, whereas the optical absorption rises in the whole
      studied wavelength range. These two phenomena seem to be related to one another.
      Furthermore, optical absorption measurements highlight the appearance of new
      absorption bands probably owing to oxygen vacancies. Induced defects are also
      observed in the EPR spectra of irradiated pellets. They are likely related to
      electronic holes trapped on oxygen ions. The concentration of these defects
      increases with ion fluence and fluorescence measurements indicate that some pre
      existing defects such as F2(2+) centres follow the same trend up to approximately
      4.1 x 10(13) ions cm(-2).

PMID- 16644990
TI  - Correlation of phase transition with the change in TL characteristics in CaSO4:Dy
      phosphor--effect of thermal treatment.
AB  - The study is aimed at optimising the glow curve structure of CaSO4:Dy phosphor
      for dosimetric purpose and also to understand the observed changes owing to
      thermal treatment in the thermoluminescence (TL) sensitivity and glow curve
      structure. The reversible changes in the intensities of the lower temperature
      satellite peak and the main dosimetric glow peak with temperature of thermal
      treatment in the temperature range 400-700 degrees C indicates the
      interconversion of defect complexes responsible for the glow peaks in CaSO4:Dy.
      Phosphor samples subjected to thermal treatment in temperature range beyond 800
      degrees C, showed irreversible changes in the intensities of the lower
      temperature and dosimetric peaks. The changes in TL characteristics of the
      phosphor for thermal treatments >800 degrees C are attributed to the partial
      phase transition in the phosphor as confirmed by the XRD and TG/DTA analysis of
      the phosphor.

PMID- 16644991
TI  - Glow peak temperature, supralinearity and LET dependence of TLDs--correlation
      studies.
AB  - The study of the well separated low and high temperature glow peaks in CaSO4:Dy
      and CaF2:Tm was undertaken to develop comparative data on supralinearity of low
      and high temperature glow peaks for their use in the estimation of elapsed time
      of exposure and to analyse their responses to low and high-linear energy transfer
      (LET) radiation. In CaSO4:Dy, unlike its dosimetric peak, the structure of glow
      peaks at approximately 140 and 400 degrees C remains unchanged (peak position
      changes within 4 degrees C) with 60Co gamma-ray exposure up to 1 kGy air kerma.
      The glow peaks at 140 degrees C exhibited higher supralinearity than that of the
      peaks at 240 and 400 degrees C. In CaF2:Tm, 110 degrees C glow peak exhibited
      higher supralinearity and higher response to high-LET radiation as compared with
      150 degrees C glow peak. No correlation between glow peak temperature and
      supralinearity or the LET response was observed.

PMID- 16644992
TI  - The MATROSHKA facility--dose determination during an EVA.
AB  - On 29 January 2004 the MATROSHKA facility was launched with a Russian Progress to
      the International Space Station. MATROSHKA is an ESA project, which has been
      achieved under the direction of the German Aerospace Center (DLR). The project is
      a cooperation of >16 research institutes from all over the world and is currently
      the biggest international experiment in radiation dosimetry ever performed in
      space. The facility simulates, as exact as possible, an astronaut during an
      extravehicular activity. It was successfully installed outside the Russian
      segment 'Zvezda' on 26 February 2004 and will remain there for a 1.5 year
      exposure period. The main task of the facility is to measure particle fluence and
      energy spectra, dose and dose rates outside and inside--including organ dose
      determination--in an anthropomorphic phantom mounted on the outside of the Space
      Station with passive and active dosemeter systems.

PMID- 16644993
TI  - Electronic neutron personal dosemeters: their performance in mixed radiation
      fields in nuclear power plants.
AB  - This work describes spectral distributions of neutrons obtained as function of
      energy and direction at four workplace fields at the Krummel reactor in Germany.
      Values of personal dose equivalent H(p)(10) and effective dose E are determined
      for different directions of a person's orientation in these fields and readings
      of personal neutron dosemeters--especially electronic dosemeters--are discussed
      with respect to H(p)(10) and E.

PMID- 16644994
TI  - In vivo EPR dosimetry to quantify exposures to clinically significant doses of
      ionising radiation.
AB  - As a result of terrorism, accident or war, populations potentially can be exposed
      to doses of ionising radiation that could cause direct clinical effects within
      days or weeks. There is a critical need to determine the magnitude of the
      exposure to individuals so that those with significant risk can have appropriate
      procedures initiated immediately, while those without a significant probability
      of acute effects can be reassured and removed from the need for further
      consideration in the medical/emergency system. It is extremely unlikely that
      adequate dosemeters will be worn by the potential victims, and it also will be
      unlikely that prompt and accurate dose reconstruction at the level of individuals
      will be possible. Therefore, there is a critical need for a method to measure the
      dose from radiation-induced effects that occur within the individual. In vivo EPR
      measurements of radiation-induced changes in the enamel of teeth is a method,
      perhaps the only such method, which can differentiate among doses sufficiently to
      classify individuals into categories for treatment with sufficient accuracy to
      facilitate decisions on medical treatment. In its current state, the in vivo EPR
      dosemeter can provide estimates of absorbed dose of +/- 0.5 Gy in the range from
      1 to >10 Gy. The lower limit and the precision are expected to improve, with
      improvements in the resonator and the algorithm for acquiring and calculating the
      dose. In its current state of development, the method is already sufficient for
      decision-making action for individuals with regard to acute effects from exposure
      to ionising radiation for most applications related to terrorism, accidents or
      nuclear warfare.

PMID- 16644995
TI  - Evaluation of a new self-developing instant film for imaging and dosimetry.
AB  - Radiation sensitive films are standard dosimetric tools in radiation therapy.
      Films are used for machine quality assurance (QA) and treatment planning software
      evaluation. With the advent of intensity modulated radiation therapy (IMRT),
      simple and fast imaging technology is needed for patient-specific verification of
      radiation fields. Conventional radiographic films are often used. Radiochromic
      films, e.g. Gafchromic films, were recently introduced to the market. But these
      films have some disadvantages. JP Laboratories have developed a prototype
      radiochromic film, called SIFID (self-developing, instant film for imaging and
      dosimetry) with superior performance such that SIFID is unaffected by ambient
      light for months, stable up to 90 degrees C and can be archived. SIFID is made of
      polymerisable diacetylene. The film develops blue colour instantly upon absorbing
      radiation. We evaluated the film for radiation therapy applications. Our
      preliminary data demonstrate its feasibility as a dosimetric tool for IMRT QA as
      well as for other applications.

PMID- 16644996
TI  - Track structure approach to the calculation of peak 5a to peak 5 (TLD-100)
      relative intensities following heavy charged particle irradiation.
AB  - A track structure approach to the calculation of the relative strength of
      localised and delocalised recombination mechanisms leading to composite glow peak
      5 in LiF:Mg,Ti following heavy charged particle irradiation is described.

PMID- 16644997
TI  - A Novel real-time dosimetry technique based on radiation-induced surface
      activation.
AB  - A novel real-time dosimetry technique based on radiation-induced surface
      activation (RISA) phenomenon has been proposed that is similar to ultraviolet
      surface activation known typically in anatase-type titanium dioxide. It has been
      found that the RISA phenomenon occurs on the surface of an oxidised semiconductor
      or oxidised metal film by radiation incidence. The RISA dosemeter has the
      following advantageous characteristics: (1) output of the RISA dosemeter is
      proportional to the dose equivalent rate in harsh environments, (2) fluctuation
      of output of the RISA dosemeter irradiated by (60)Co gamma-rays is <2.5% beyond
      the total dose equivalent of 1.8 MSv, (3) the transient current observed in
      simple insulators for a few seconds or more after onset of irradiation was not
      detected in the RISA dosemeter and (4) this dosemeter worked well even at high
      temperatures.

PMID- 16644998
TI  - Ionisation density dependence of the optically stimulated luminescence dose
      response of AL2O3:C to low-energy charged particles.
AB  - The optically stimulated luminescence (OSL) response of Al2O3:C to high doses of
      gamma or beta irradiation can be used to predict the response of this material to
      charged particles as a function of particle fluence, particle energy and/or
      linear energy transfer (LET). In particular, it is predicted that track
      interaction effects at high particle fluences should result in linear-sublinear
      growth of the OSL signal. Similar considerations also predict a dependence of the
      fluence at which sublinearity starts upon the energy of the particles. In this
      work the OSL response of Al2O3:C to low-energy charged particles was investigated
      using protons (1, 2 and 4 MeV), carbon ions (13 MeV) and oxygen ions (10 MeV).
      The sublinear growth predicted above was qualitatively confirmed, but the energy
      dependence prediction was not. Furthermore, the efficiency of OSL production in
      the material after charged particle irradiation, compared to that obtained for
      gamma irradiation, is determined from the dose-response curves by fitting to a
      simple saturating exponential function. The efficiency values so obtained using
      this method are compared with those obtained from a conventional single-point
      measurement in the linear portion of the curve and found to be in good agreement.
      In general, the efficiency decreases as the LET of the particle increases. The
      present data are compared with published data obtained using high-energy charged
      particles and the results show that the efficiency is not a unique function of
      LET.

PMID- 16644999
TI  - Deep-trap competition model for TL in alpha-Al2O3:C heating stage.
AB  - The present report deals with the experimental observations of the thermally
      stimulated migration of charge carriers from trapping centres responsible for the
      main thermoluminescence (TL) peak at 450 K to a deep trap and, also, the
      optically stimulated transport of carriers from the deep trap to the main trap,
      which gives rise to the phototransferred TL at 450 K, in anion-defective alpha
      Al2O3 crystals. The obtained results provide an experimental proof to the
      adequacy of the assumptions made in the model of the mutual interaction of the
      main and deep traps in the crystals under study.

PMID- 16645000
TI  - A study of the irradiation temperature coefficient for L-alanine and DL-alanine
      dosemeters.
AB  - Alanine dosimetry is now well established both as a reference and routine
      dosemeter for industrial irradiation processing. Accurate dosimetry under the
      relatively harsh conditions of industrial processing requires a characterisation
      of the parameters that influence the dosemeter response. The temperature of the
      dosemeter during irradiation is a difficult quantity to measure so that the
      accuracy of the temperature coefficient that governs the dosemeter response
      becomes a critical factor. Numerous publications have reported temperature
      coefficients for several types of alanine dosemeters. The observed differences in
      the measured values were commonly attributed to the differences in the polymer
      binder or the experimental design of the measurement. However, the data
      demonstrated a consistent difference in the temperature coefficients between l
      alanine and dl-alanine. Since there were no commonalities in the dosemeter
      composition or the measurement methods applied, a clear conclusion is not
      possible. To resolve this issue, the two isomeric forms of alanine dosemeters
      were prepared and irradiated in an identical manner. The results indicated that
      the dl-alanine temperature coefficient is more than 50% higher than the l-alanine
      temperature coefficient.

PMID- 16645001
TI  - Indoor radon concentration in the rural dwellings of Chhattisgarh state (India).
AB  - Inhalation of radon and its daughter products is the major contributor to the
      total exposure of the population to natural radiation. An indoor radon survey has
      been carried out in the state of Chhattisgarh (80.26 degrees N to 84.41 degrees N
      and 17.8 degrees E to 24.1 degrees E), India under the national coordinated radon
      project of the Department of Atomic Energy. In the frame of this project indoor
      radon concentration has been measured in 105 dwellings situated in different
      villages of Chhattisgarh state. Houses were selected for measurements to cover
      the most common type of houses generally existing in the rural areas.
      Measurements have been done on quarterly integrating cycle for one full year in
      each dwelling using radon cup dosemeter employing LR-115, type-II (pelliculable),
      solid-state nuclear track detectors. The gamma radiation level was also checked
      in each dwelling using a gamma survey meter. It was found that the annual average
      indoor radon concentration in these dwellings varies from 9.91 to 87.84 Bq m(-3)
      with overall mean value of 26.48 Bq m(-3). Gamma level in these rural dwellings
      varies from 14.84 to 26.56 microR h(-1) with mean value of 18.68 microR h(-1). We
      observed that the radon concentration is relatively higher in the houses where
      the floor is bare but relatively lower in those houses where the floor is tiled
      or cemented.

PMID- 16645002
TI  - Study of materials for mixed field dosimetry by EPR spectroscopy.
AB  - EPR dose reconstruction after accidental photon exposure based on materials
      irradiated in the vicinity of the victim (sucrose, medicine tablets, etc.) was
      used successfully in several cases referenced in the literature. However,
      accidental exposure may also occur with a neutron component such as in the Tokai
      Mura criticality accident. The aim of this work is to investigate the
      potentiality of EPR dosimetry for mixed photon and neutron field exposure with
      different organic materials already used for photon exposure (sucrose) or with
      potential dosimetric properties (ascorbic acid, sorbitol, glucose, galactose,
      fructose, lactose and mannose). To assess the neutron sensitivity, the materials
      were exposed to a mixed radiation field of an experimental reactor with different
      neutron to photon ratios. The relative neutron sensitivity was found to range
      from 12 to 43% according to the materials. The potentiality of these materials
      for mixed field EPR dosimetry is discussed.

PMID- 16645003
TI  - On changes and passings.

PMID- 16645004
TI  - Defective nitric oxide-dependent, deaminative cleavage of glypican-1 heparan
      sulfate in Niemann-Pick C1 fibroblasts.
AB  - Exit of recycling cholesterol from late endosomes is defective in Niemann-Pick C1
      (NPC1) and Niemann-Pick C2 (NPC2) diseases. The traffic route of the recycling
      proteoglycan glypican-1 (Gpc-1) may also involve late endosomes and could thus be
      affected in these diseases. During recycling through intracellular compartments,
      the heparan sulfate (HS) side chains of Gpc-1 are deaminatively degraded by
      nitric oxide (NO) derived from preformed S-nitroso groups in the core protein. We
      have now investigated whether this NO-dependent Gpc-1 autoprocessing is active in
      fibroblasts from NPC1 disease. The results showed that Gpc-1 autoprocessing was
      defective in these cells and, furthermore, greatly depressed in normal
      fibroblasts treated with U18666A (3-beta-[2-(diethylamino)ethoxy]androst-5-en-17
      one), a compound widely used to induce cholesterol accumulation. In both cases,
      autoprocessing was partially restored by treatment with ascorbate which induced
      NO release, resulting in deaminative cleavage of HS. However, when NO-dependent
      Gpc-1 autoprocessing is depressed and heparanase-catalyzed degradation of HS
      remains active, a truncated Gpc-1 with shorter HS chains would prevail, resulting
      in fewer NO-sensitive sites/proteoglycan. Therefore, addition of ascorbate to
      cells with depressed autoprocessing resulted in nitration of tyrosines. Nitration
      was diminished when heparanase was inhibited with suramin or when Gpc-1
      expression was silenced by RNAi. Gpc-1 misprocessing in NPC1 cells could thus
      contribute to neurodegeneration mediated by reactive nitrogen species.

PMID- 16645005
TI  - Environmental chemicals and thyroid function.
AB  - There is growing evidence that environmental chemicals can disrupt endocrine
      systems. Most evidence originates from studies on reproductive organs. However,
      there is also suspicion that thyroid homeostasis may be disrupted. Several groups
      of chemicals have potential for thyroid disruption. There is substantial evidence
      that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in
      exposed animals and that environmentally occurring doses affect human thyroid
      homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH)
      levels in rodents, but human studies are scarce. Studies also indicate thyroid
      disruptive properties of phthalates, but the effect of certain phthalates seems
      to be stimulative on TH production, contrary to most other groups of chemicals.
      Thyroid disruption may be caused by a variety of mechanisms, as different
      chemicals interfere with the hypothalamic-pituitary-thyroid axis at different
      levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid
      peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular
      uptake mechanisms. The peripheral metabolism of the THs can be affected through
      effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in
      thyroid homeostasis may adversely affect human health, and especially fetal
      neurological development may be vulnerable. It is therefore urgent to clarify
      whether the animal data showing effects of chemicals on thyroid function can be
      extended to humans.

PMID- 16645006
TI  - Peroxisome proliferator-activated receptor gamma agonists in renal disease.
AB  - Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only
      few oral antidiabetic drugs can be used for treating type 2 diabetes in patients
      with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser,
      and peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such
      as rosiglitazone and pioglitazone. These compounds are metabolised in the liver,
      therefore accumulation of the drug and the risk of severe and prolonged
      hypoglycaemia are minimised. PPARgamma receptors are expressed in many tissues
      including the kidney. Recently, numerous healthful effects of PPARgamma agonists
      on several aspects related to renal function have been increasingly reported.
      These drugs have shown to possess many advantageous anti-inflammatory,
      haemodynamic, vascular and metabolic effects. In the present paper we have
      reviewed the more recent experimental studies that evaluated these potential
      beneficial effects of PPARgamma agonists on renal function and revised the
      results of their utilisation in patients with different degrees of renal
      impairment, in dialysis patients, and in patients with diabetes mellitus after
      kidney transplantation. Finally, tolerability and safety profile of PPARgamma
      agonists in patients with reduced glomerular filtration rate are also analysed.

PMID- 16645007
TI  - The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20
      antibody therapy as a novel treatment option.
AB  - We have reviewed the immunology of thyroid autoimmunity with special reference to
      the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves'
      disease (GD), thus providing a framework for the hypothesis that B cell depletion
      may be beneficial in GD. Additionally, after reviewing the efficacy and safety in
      other autoimmune diseases, we propose that treatment with the B cell-depleting
      agent Rituximab may become a clinically relevant treatment option in selected
      cases of GD, particularly when complicated with thyroid-associated
      ophthalmopathy.

PMID- 16645008
TI  - Is there a need to redefine the upper normal limit of TSH?
AB  - Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been
      discussed as being a risk factor for the development of overt thyroid dysfunction
      and for a number of clinical disorders. The diagnosis critically depends on the
      definition of the upper normal limit of serum TSH as, by definition, free
      thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have
      been conventionally used to diagnose an elevated TSH serum concentration. Recent
      data from large population studies have suggested a much lower TSH cut-off with
      an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of
      subjects from the general population studies aiming at assessing TSH reference
      intervals (no personal or family history of thyroid disease, no thyroid
      antibodies and a normal thyroid on ultrasonography) did not result in an
      unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the
      available evidence for lowered upper TSH cut-off values and their potential
      therapeutic implications there is presently insufficient justification to lower
      the upper normal limit of TSH and, for practical purposes, it is still
      recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying
      subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as
      intervening with thyroxine treatment in such subjects, is probably doing more
      harm than good.

PMID- 16645009
TI  - A pituitary carcinoma secreting TSH and prolactin: a non-secreting adenoma gone
      awry.
AB  - To our knowledge, only one case of a TSH-secreting carcinoma has previously been
      reported. We describe here a second patient with a pituitary carcinoma producing
      TSH and prolactin (PRL). A 37-year-old male underwent a left frontotemporal
      craniotomy in 1996 for a sellar mass. Except for mildly increased PRL and
      elevated alpha-subunit, hormone evaluation was normal. Pathologic examination
      revealed a chromophobe adenoma with increased mitotic forms. The patient
      completed a course of external beam radiation to the pituitary and was prescribed
      l-thyroxine, bromocriptine, and hydrocortisone. He was lost to follow-up but did
      well for 6 years, until 2002, when he presented with TSH-dependent thyrotoxicosis
      and hyperprolactinemia. The patient was started on bromocriptine and
      propylthiouracil and was, again, lost to follow-up. In 2004, 9 years after his
      initial presentation, he presented after falling. Magnetic resonance imaging
      showed two brain masses with associated midline shift. Emergent resection of the
      larger mass revealed a pituitary cancer with positive staining for PRL, but not
      for TSH. Nine months later, the patient underwent further debulking of metastatic
      disease. Although development of a carcinoma from a pituitary adenoma is very
      rare (<0.5%), macroadenomas that become hormonally active should be suspect for
      transformation into pituitary cancer.

PMID- 16645010
TI  - Thyroid autoimmunity in patients with malignant and benign breast diseases before
      surgery.
AB  - BACKGROUND: Previous studies have demonstrated a high prevalence of
      thyroperoxidase antibodies (TPOAb) and autoimmune hypothyroidism in breast cancer
      (BC). These studies have been performed in BC patients generally 20-30 days after
      mastectomy. It is known that stress may have an influence on the immune system
      and a relation between stressful events and the onset or worsening of autoimmune
      thyroid disorders has been reported by several authors. The aim of the study was
      to evaluate the prevalence of autoimmune thyroid disease in patients with nodular
      breast disease selected for surgery before any treatment. Our hypothesis was that
      the high prevalence of thyroid autoimmune disorders in BC is independent of
      stressful events represented by surgery and/or anaesthetic procedures. METHODS:
      Our series included 61 consecutive women aged 52.8 +/- 10.2 yrs (mean age +/-
      s.d.) with nodular breast disease selected for breast surgery: 36 out of 61 of
      them (59%) had BC and 25 out of 61 had benign breast disease (BBD). Controls
      included 100 healthy age-matched women. All patients and control subjects were
      submitted to clinical, ultrasound thyroid evaluation and serum-free thyroxine
      (FT4), serum-free tri-iodothyronine (FT3), TSH, TPOAb and thyroglobulin
      antibodies (TgAb) determination. RESULTS: Mean FT3, FT4 and TSH concentration
      showed no differences between BC patients, BBD patients and controls. The
      prevalence of TPOAb in BC patients (12/36: 33.33%) was significantly higher than
      in BBD patients (5/25: 20%) (P < 0.01) and in controls (8/100: 8%) (P < 0.01).
      Similarly, the prevalence of TgAb in BC patients was 12 out of 36 (33.33%)
      significantly higher than that detected in BBD patients (4/25: 16%) (P < 0.01)
      and in controls (12/100: 12%) (P < 0.01). Of the 36 BC patients, 20 showed a
      diffuse hypoechogenicity of the thyroid gland to ultrasound evaluation,
      significantly higher than in BBD (7/25: 28%) (P = 0.03). Of the 20 BC patients
      who showed a hypoechogenic pattern of thyroid gland, 10 (50%) were associated
      with antithyroid antibodies positivity (TAb). This finding was present in two of
      seven BBD (28.57%) (P < 0.0001). Only two controls showed focal hypoechogenicity
      of the thyroid gland. Generally, 24 out of 36 (66.7%) of BC and 9 out of 25 (36%)
      of BBD (P = 0.02) had signs of thyroid autoimmunity consistent with the
      hypoechogenic pattern of thyroid gland associated or not with TAb; 2 out of 36
      (5.55%) of BC and 1 out of 25 (4%) of BBD patients had autoimmune hypothyroidism
      and no hypothyroidism was found in controls. CONCLUSIONS: The results of this
      study confirm the strong relation between thyroid autoimmunity and BC. This
      finding is independent of stressful events represented by surgery or anaesthetic
      procedures. The present data call attention to the usefulness of screening for
      autoimmune thyroid disorders in patients with nodular breast disease selected for
      surgery.

PMID- 16645011
TI  - Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not
      associated with hyper- or hypothyroidism per se, but is specifically sustained by
      the autoimmune, inflammatory process.
AB  - OBJECTIVE: Serum CXCL10 (an interferon-gamma-inducible chemokine) levels
      (sCXCL10) are increased in several autoimmune conditions, including Graves'
      disease (GD) and autoimmune thyroiditis (AT). Longitudinal assessment of sCXCL10
      in autoimmune hypo- or hyperthyroidism has not yet been performed. DESIGN AND
      METHODS: We longitudinally assayed sCXCL10 in the following groups: thirty-three
      GD and 11 toxic nodular goiter (TNG) patients when hyperthyroid (Hyper) and when
      reaching euthyroidism (Eu) with methimazole therapy (MMI) sixty-six AT (33
      hypothyroid (Hypo) and 33 Eu) patients, basally and after reaching EU (for Hypo)
      with levothyroxine (L-T4) therapy twenty-two patients with thyroid cancer (CA)
      under L-T4-suppressive treatment, of whom 11 were re-evaluated after L-T4
      withdrawal for diagnostic WBS, and 11 after recombinant TSH (rhTSH)
      administration thirty-three healthy controls. RESULTS: At initial evaluation,
      Hyper GD and AT (Hypo significantly higher than Eu) showed significantly higher
      mean sCXCL10 than all other groups. MMI treatment led to a significant decrease
      in sCXCL10 only in GD (not in TNG), while restoration of Eu, in Hypo AT, by L-T4
      was not accompanied by significant sCXCL10 change. CA showed sCXCL10 comparable
      to controls, and both Hypo after L-T4 withdrawal and rhTSH injection had no
      effect on sCXCL10. CONCLUSIONS: Treatment of Hyper leads to a significant
      decrease in sCXCL10 only in GD, and this probably depends upon the MMI
      immunomodulatory effect. L-T4 correction of Hypo is not accompanied by
      significant modification of sCXCL10 in AT. Increased sCXCL10 is not associated
      with Hyper or Hypo per se, but is specifically sustained by the autoimmune
      inflammatory event occurring in both GD and AT.

PMID- 16645012
TI  - Ghrelin test for the assessment of GH status in successfully treated patients
      with acromegaly.
AB  - OBJECTIVE: Posttreatment assessment of disease activity and definition of cure of
      acromegaly, using measurement of GH secretion, remains problematic. Furthermore,
      with our efforts to achieve tight biochemical control of the disease it is
      foreseeable that a proportion of patients may be rendered GH deficient, thus
      requiring testing for GH deficiency. The aim of our study was to evaluate
      residual GH secretion in cured patients with acromegaly. DESIGN AND METHODS: At
      baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri
      glycerides) levels were measured in 33 acromegalic patients nine years after
      treatment with surgery of whom 6 were additionally irradiated. Two tests were
      performed: the GH suppression test--oral glucose tolerance test (OGTT) and the GH
      provocation test--ghrelin test (1 microg/kg i.v. bolus) and the results were
      compared with 11 age- and sex-matched control subjects. RESULTS: According to the
      consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 microg/l), 21
      treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir
      values during OGTT, while 6 had persistent acromegaly. After the GH provocative
      test with ghrelin (cut-off for severe GH deficiency is GH <3 microg/l), we
      detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic
      patients. Mean GH peak (+/-s.e.m.) response to the ghrelin test in GHD
      acromegalics was significantly lower compared with acromegalics with sufficient
      GH secretory capacity and control subjects (1.2 +/- 0.2 microg/l vs 20.1 +/- 2.4
      microg/l vs 31.1 +/- 2.5 microg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3
      levels were not different between GHD and GH-sufficient cured acromegalics.
      Leptin levels and body mass index (BMI) were significantly higher in GHD male
      acromegalics compared with GH-sufficient male acromegalics. GHD female
      acromegalics tended to have higher BMIs while leptin levels were not different.
      CONCLUSIONS: The assessment of residual GH secretory capacity by the GH
      provocation test is necessary in the long-term follow-up of successfully treated
      acromegalics since a large proportion of these patients are rendered GH
      deficient.

PMID- 16645013
TI  - Free fatty acids decrease circulating ghrelin concentrations in humans.
AB  - OBJECTIVE: Concentrations of the orexigenic peptide ghrelin is affected by a
      number of hormones, which also affect circulating levels of free fatty acids
      (FFAs). The present study was therefore designed to determine the direct effect
      of FFAs on circulating ghrelin. DESIGN: Eight lean, healthy men were examined for
      8 h on four occasions using variable infusion rates (0, 3, 6 and 12 microl/kg per
      min) of intralipid to create different plasma FFA concentrations. Constant levels
      of insulin and GH were obtained by administration of acipimox (250 mg) and
      somatostatin (300 microg/h). At the end of each study day a hyperinsulinaemic
      euglycaemic clamp was performed. RESULTS: Four distinct levels of FFAs were
      obtained at the end of the lipid infusion period (FFA(LIPID): 0.03 +/- 0.00 vs:
      0.49 +/- 0.04, 0.92 +/- 0.08 and 2.09 +/- 0.38 mmol/l; ANOVA P < 0.0001) and
      during hyperinsulinaemia (FFA(LIPID+INSULIN): 0.02 +/- 0.00 vs: 0.34 +/- 0.03,
      0.68 +/- 0.09 and 1.78 +/- 0.32 mmol/l; ANOVA P < 0.0001). Whereas, somatostatin
      infusion alone reduced ghrelin concentration by approximately 67%, concomitant
      administration of increasing amounts of intralipid reduced circulating ghrelin by
      a further 14, 19 and 19% respectively (change in ghrelin: 0.52 +/- 0.05 vs: 0.62
      +/- 0.06, 0.72 +/- 0.09 and 0.71 +/- 0.05 microg/l; ANOVA P = 0.04). No further
      reduction in ghrelin concentration was observed during hyperinsulinaemia.
      CONCLUSION: FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin
      levels independent of ambient GH and insulin levels.

PMID- 16645014
TI  - Transsphenoidal pituitary surgery via the endoscopic technique: results in 35
      consecutive patients with Cushing's disease.
AB  - OBJECTIVE AND DESIGN: The endoscopic technique has been recently introduced in
      the field of transsphenoidal pituitary surgery. This technique allows inspection
      of sellar, supra- and parasellar structures and removal of the tumor under direct
      visualization, is minimally traumatic and permits easier reoperations. This is
      the first report on the results of endoscopic surgery for patients with Cushing's
      disease. Our aim was to retrospectively analyze the results of pituitary surgery
      in 35 consecutive patients with Cushing's disease operated in our hospital after
      the introduction of the endoscopic technique (1998-2004). METHODS: Remission was
      defined as suppression of plasma cortisol (< or =50 nmol/L) after 1 mg
      dexamethasone overnight determined in the first 3 months after surgery and
      disappearance of clinical signs and symptoms of hypercortisolism. The patients
      were followed for an average of 27 months (range 4 to 81 months, median 20
      months). RESULTS: Pituitary MRI showed a macroadenoma in 6 patients, a
      microadenoma in 17 patients and no adenoma in 12 patients. After the initial
      surgery 27 patients (77%) were in remission. None of the patients had a relapse
      during follow-up. In the remaining 8 patients hypercortisolemia persisted after
      surgery. Three of them had a second endoscopic pituitary surgery resulting in
      remission in two patients. In one patient a second endoscopic pituitary surgery
      will soon follow. The remaining four patients were treated with radiotherapy
      postoperatively. Two of them were at the time of data collection in remission.
      One patient from the remission group had a serious epistaxis and three patients
      had cerebrospinal fluid leakage, one requiring an external lumbar drain, shortly
      after surgery. No complications were recorded in the failure group.
      Postoperatively 34% of all patients required substitution with levothyroxine, 40%
      required substitution with glucocorticoids, 17% received estrogens or
      testosterone and 6% still required desmopressin. CONCLUSIONS: Endoscopic
      transsphenoidal pituitary surgery resulted in our series of patients with
      Cushings disease in an excellent postoperative remission rate. A randomized
      clinical trial, comparing endoscopic and conventional pituitary surgery in
      patients with Cushings disease, is needed to determine the pros and cons of both
      techniques.

PMID- 16645015
TI  - DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis
      in five patients.
AB  - OBJECTIVE: Mutations in the gene coding for the orphan nuclear receptor DAX1
      cause X-linked adrenal hypoplasia congenita (AHC). Affected boys usually present
      with primary adrenal failure in early infancy or childhood. Impaired sexual
      development due to hypogonadotropic hypogonadism becomes manifest at the time of
      puberty. Moreover, evidence from Dax1 knockout mice and a limited number of
      patients with AHC, suggests that mutations in DAX1 may directly cause
      abnormalities in spermatogenesis. The aim of this study was to characterize
      clinically and genetically five patients with AHC. DESIGN: DNA sequencing
      analysis, endocrine testing, testicular ultrasound and semen analysis with 1-year
      follow-up after gonadotropin treatment. METHODS: We report on five men with
      classic AHC manifestations. Genomic DNA was extracted from patients' peripheral
      blood leukocytes and the coding region, splice sites, and promoter (-240 bp)
      region of DAX1 were directly sequenced. RESULTS: Three known and two novel
      mutations were detected in the DAX1 coding sequence in these patients. Semen
      analysis was performed in four of the five patients and showed azoospermia.
      Twelve-month treatment with gonadotropins did not restore fertility in these
      patients. All patients showed a normal testicular Doppler ultrasound, in contrast
      with that observed in Dax1-deficient mice, which display abnormalities in the
      rete testis. CONCLUSIONS: These cases further expand the number of DAX1 mutations
      reported in the literature, as well as our clinical knowledge of this rare
      disease.

PMID- 16645016
TI  - Increased T-helper interferon-gamma-secreting cells in obese children.
AB  - OBJECTIVE: Leptin, an adipocyte-secreted hormone, has emerged as a potential
      candidate for the link between obesity and the proinflammatory state.
      Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with
      the secretion of proinflammatory cytokines. The aim of this study was to evaluate
      the Th1/Th2 balance in obese children and its relation with hormonal and
      metabolic features. STUDY DESIGN: In 50 obese children and 20 control children,
      we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or
      interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index
      of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index
      (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases,
      leptin and ghrelin. Obese children also underwent dual energy X-ray
      absorptiometry scan measurements, and liver ultrasound scanning. RESULTS:
      Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese
      children were not significantly different from those found in control children.
      However, the geometric mean percentage of CD4-positive T cells secreting IFN
      gamma was significantly higher in the obese than in the control (P < 0.0001, t
      test) group. Within the entire group of study children, the percentage of IFN
      gamma-positive cells was positively associated with leptin (P = 0.002), insulin
      (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these
      associations were restricted to the group of obese subjects, insulin and HOMA-IR
      values, but not leptin, retained statistical significance. Yet, in the obese
      group, the percentage of IFN-gamma-positive cells was associated with
      nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index
      standard deviation score and total body fat mass. CONCLUSIONS: In obese children,
      a shift to Th1-cytokine profile dominated by the production of IFN-gamma is
      related to insulin resistance as well as to NASH independently of anthropometric
      features and other metabolic characteristics. The prevalent Th1 pattern of
      secreted cytokines may be regarded as a mechanism contributing to inflammation in
      obesity.

PMID- 16645017
TI  - Opposite associations of age-dependent insulin-like growth factor-I standard
      deviation scores with nutritional state in normal weight and obese subjects.
AB  - OBJECTIVE: Insulin-like growth factor-I (IGF-I) has been suggested to be a
      prognostic marker for the development of cancer and, more recently,
      cardiovascular disease. These diseases are closely linked to obesity, but reports
      of the association of IGF-I with measures of obesity are divergent. In this
      study, we assessed the association of age-dependent IGF-I standard deviation
      scores with body mass index (BMI) and intra-abdominal fat accumulation in a large
      population. DESIGN: A cross-sectional, epidemiological study. METHODS: IGF-I
      levels were measured with an automated chemiluminescence assay system in 6282
      patients from the DETECT study. Weight, height, and waist and hip circumference
      were measured according to the written instructions. Standard deviation scores
      (SDS), correcting IGF-I levels for age, were calculated and were used for further
      analyses. RESULTS: An inverse U-shaped association of IGF-I SDS with BMI, waist
      circumference, and the ratio of waist circumference to height was found. BMI was
      positively associated with IGF-I SDS in normal weight subjects, and negatively
      associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of
      22.5-25 kg/m2 in men (+0.08), and at a BMI of 27.5-30 kg/m2 in women (+0.21).
      Multiple linear regression models, controlling for different diseases,
      medications and risk conditions, revealed a significant negative association of
      BMI with IGF-I SDS. BMI contributed most to the additional explained variance to
      the other health conditions. CONCLUSIONS: IGF-I standard deviation scores are
      decreased in obesity and underweight subjects. These interactions should be taken
      into account when analyzing the association of IGF-I with diseases and risk
      conditions.

PMID- 16645018
TI  - Are serum leptin and the Gln223Arg polymorphism of the leptin receptor
      determinants of bone homeostasis in elderly men?
AB  - OBJECTIVE: Across studies it has been suggested that leptin intervenes as a
      regulator of bone metabolism. This study assesses the contribution in elderly men
      of leptin and the Gln223Arg leptin receptor gene (LEPR) polymorphism to the
      variation in bone homeostasis, in relation to body composition and free estradiol
      as major confounders. DESIGN: We performed cross-sectional (n = 270) and
      longitudinal (mean follow-up 3.4 years, n = 214) evaluations in elderly men.
      METHODS: Serum leptin, LEPR genotype, baseline bone mineral density (BMD),
      longitudinal BMD changes at the hip and forearm, and biochemical markers of bone
      turnover were determined. RESULTS: In cross-sectional analyses absolute fat mass
      was the index of body composition most strongly associated with leptin (r = 0.74;
      P < 0.001). LEPR genotypes and serum leptin were not associated. Serum bone
      specific alkaline phosphatase (S-BAP) was associated with LEPR genotypes (P =
      0.05) and urinary C-terminal telopeptides of type I collagen (U-CTX) were
      associated with leptin levels (P = 0.03), independently from age, fat mass and
      free estradiol. Baseline BMD at the hip and forearm was neither associated with
      leptin nor with LEPR genotypes. Prospectively assessed BMD loss was not
      associated with serum leptin at the hip, whereas BMD loss was positively
      associated with leptin at the forearm (P = 0.01), independently from age, fat
      mass and free estradiol. Longitudinal changes in hip or forearm BMD were not
      associated with LEPR genotypes. CONCLUSION: The findings suggest a possible role
      for leptin as determinant of bone homeostasis in elderly men, but with only
      modest impact independently from body composition and free estradiol.

PMID- 16645019
TI  - An insulin-like growth factor-I gene polymorphism modifies the risk of
      microalbuminuria in subjects with an abnormal glucose tolerance.
AB  - OBJECTIVE: Microalbuminuria (MA) is related to cardiovascular disease both in
      diabetic patients and non-diabetic subjects. DESIGN: We investigated whether a
      polymorphism near the promoter region of the IGF-I gene was related to the
      development of MA. METHODS: For this study, 1069 participants of the Rotterdam
      study were selected (440 participants with an abnormal glucose tolerance (AGT),
      220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595
      subjects with a normal glucose tolerance (NGT). RESULTS: 787 subjects were
      carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant
      carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT
      the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2-7.7);
      P = 0.02) in variant carriers with AGT than in carriers of the wild type of this
      IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2-4.0); P = 0.009). Compared with
      wild type carriers with AGT, the relative risk for MA was unadjusted and non
      significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8-2.9).
      However, after adjustment for possible confounding factors (age, gender, mean
      blood pressure, fasting insulin, fasting glucose and smoking) this risk became
      significant (OR: RR 2.1; 95% CI:1.1-4.4; P = 0.04). CONCLUSIONS: In subjects with
      AGT, a higher risk for MA was observed in variant carriers than in carriers of
      the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily
      associated with cardiovascular disease in subjects with AGT, our study suggests
      that variant carriers have a higher risk for cardiovascular disease than carriers
      of the wild type when they develop an AGT.

PMID- 16645020
TI  - An alternative spliced variant of circulating soluble tumor necrosis factor-alpha
      receptor-2 is paradoxically associated with insulin action.
AB  - OBJECTIVE: Serum concentrations of soluble tumor necrosis factor-alpha (TNF
      alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent
      study, we provided evidence for the existence of a biologically active form of
      sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether
      this circulating DS-TNFR2 is associated with insulin action in humans. DESIGN AND
      METHODS: Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in
      monocytes. 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. Insulin sensitivity was
      measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model
      of assessment (HOMA) value in a replication study of 223 subjects. RESULTS: Real
      time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy
      subjects. A significant and positive association was found between serum DS-TNFR2
      concentration and insulin sensitivity (P = 0.032, n = 76). This association was
      most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002).
      The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than
      those with undetectable DS-TNFR2 (42.12+/-22.08 vs 31.71+/- 16.95 micromol x kg(
      1) x min(-1), P = 0.039). DS-TNFR2 was inversely associated with body mass index,
      waist-to-hip ratio, systolic and diastolic blood pressure, fasting serum glucose,
      serum triglycerides and serum uric acid concentration and with the HOMA value (P
      = 0.03) in the replication study. Circulating DS-TNFR2 declined with increased
      number of components of the metabolic syndrome. CONCLUSION: Native sTNFR2 and DS
      TNFR2 show opposite associations with insulin action. DS-TNFR2 might play a role
      as a counterpart of the proinflammatory environment associated with insulin
      resistance.

PMID- 16645021
TI  - Effects of free fatty acids on ACTH and cortisol secretion in anorexia nervosa.
AB  - OBJECTIVE: Free fatty acids (FFAs) exert a stimulatory effect on the hypothalamic
      pituitary-adrenal (HPA) axis in animals and inhibit spontaneous ACTH and cortisol
      secretion in humans. Patients with anorexia nervosa display concomitant HPA axis
      hyperactivity and increased lipolysis. We studied the effects of a lipid load on
      ACTH and cortisol secretion in patients with anorexia nervosa in comparison with
      normal subjects. DESIGN: Eight women with anorexia nervosa (ANW; means +/-
      s.e.m.: 23.9 +/- 2.3 years of age; body mass index (BMI): 14.9 +/- 0.6 kg/m2) and
      seven normal women (NW; 25.6 +/- 2.3 years of age; BMI: 22.8 +/- 1.9 kg/m2) had
      FFA, ACTH, cortisol, glucose and insulin levels measured in the morning every 30
      min for 180 min during i.v. saline or lipid-heparin emulsion (LHE) infusion.
      RESULTS: During saline infusion, ACTH and cortisol levels decreased spontaneously
      in both groups, ACTH and cortisol levels in ANW being higher than in NW. LHE
      infusion led to increased FFA levels in both groups (P < 0.005). The ACTH and
      cortisol decrease in NW was more marked than during saline infusion (P < 0.05).
      LHE infusion in ANW was associated with a more pronounced decrease in ACTH levels
      than during saline infusion (P < 0.05), while cortisol levels were unchanged. At
      the end of the LHE infusion, a progressive decrease in FFA levels was associated
      with an increase in ACTH and cortisol concentrations in NW (P < 0.05) but not in
      ANW in whom FFA levels decreased to a lesser extent (P < 0.05). CONCLUSIONS: This
      study showed that corticotroph sensitivity to the inhibitory effect of an FFA
      load is preserved in patients with anorexia nervosa, in spite of persistent
      adrenal hyperactivity.

PMID- 16645022
TI  - Mutations and sequence variants in GDF9 and BMP15 in patients with premature
      ovarian failure.
AB  - BACKGROUND AND OBJECTIVE: Mutations in bone morphogenic protein 15 (BMP15) and
      growth/differentiation factor 9 (GDF9) lead to altered fertility in animal
      models. In the human, a heterozygous point mutation of BMP15 has been associated
      with premature ovarian failure (POF). SUBJECT AND METHODS: We have directly
      sequenced both genes in a cohort of 203 POF patients presenting with primary or
      secondary amenorrhea and high FSH levels and in a control population including 54
      women with regular menstrual cycles who had at least one child. RESULTS: We have
      identified several heterozygous variants. One alteration in GDF9 (S186Y) and one
      in BMP15 (L148P) may have pathogenic effects as both positions are conserved in
      vertebrate species, ranging from the chicken to mammals. These variants were
      absent in the control samples. We also found synonymous and neutral
      substitutions. CONCLUSIONS: We propose that although mutations in BMP15 and GDF9
      are not a major cause of ovarian insufficiency, they may be involved in POF.

PMID- 16645023
TI  - High-dose glucocorticoids increase serum levels of soluble IL-6 receptor alpha
      and its ratio to soluble gp130: an additional mechanism for early increased bone
      resorption.
AB  - OBJECTIVE: Glucocorticoids (GCs) at pharmacological doses stimulate bone
      resorption. Mechanisms of this action are unclear. The osteoclastogenic cytokine
      interleukin (IL)-6 acts through an oligomeric receptor consisting of two
      subunits, gp80 (or IL-6 receptor alpha, IL-6Ralpha) and gp130; both exist in
      membrane and soluble forms. Soluble IL-6Ralpha (sIL-6Ralpha) enhances, while
      sgp130 inhibits IL-6 signalling. In vitro, GCs enhance many effects of IL-6 by up
      regulation of IL-6Ralpha. The aim of the present study was to assess acute
      changes of IL-6 system in the peripheral blood of patients given high-dose GCs.
      SUBJECTS AND METHODS: Serum levels of IL-6, sIL-6Ralpha, sgp130 and bone turnover
      markers were assessed before and each day during treatment in 24 multiple
      sclerosis (MS) patients undergoing high-dose (prednisolone, 15 mg/kg per day),
      short-term (3 to 5 days) intravenous GC therapy for relapse at the Regional
      Multiple Sclerosis Centre. RESULTS: An immediate and marked fall of osteocalcin
      and an early increase of C-terminal telopeptide of type I collagen were already
      noticed at day 2 (P < 0.001 and P < 0.02, respectively); both became more
      apparent in the subsequent days. IL-6 was always below or near the detection
      limit of our ELISA. sgp130 showed a slight increase. sIL-6Ralpha significantly
      increased, peaking at day 4 (P < 0.01). However, inter-individual variability of
      response was noticed. Four patients showed a slight decrease, while no change was
      observed in one patient and an increase was noticed in the remaining nineteen
      (maximum change ranging from +10% to +67% with respect to baseline). In these
      patients, a significant increase of sIL-6Ralpha/sgp130 ratio was apparent. No
      correlation was found between bone turnover markers and any measured component of
      the IL-6 system. CONCLUSIONS: sIL-6Ralpha and sIL-6Ralpha/sgp130 ratio are
      precociously increased in the peripheral blood of the vast majority of patients
      given high-dose, intravenous GCs. The increase of systemically available sIL
      6Ralpha conceivably results in the enhancement of IL-6-dependent
      osteoclastogenesis. The role of such a mechanism in the bone loss observed in
      inflammatory and immune-mediated diseases (where abundancy of IL-6 in the bone
      microenvironment is expected) requires further investigation.

PMID- 16645024
TI  - Subclinical adenomas in postmortem pituitaries: classification and correlations
      to clinical data.
AB  - OBJECTIVE: The aim of this study was to examine pituitary adenomas in a series of
      postmortem pituitaries by use of modern technologies of immunostaining, to
      classify the adenomas according to the current WHO classification and to analyse
      the possible associations to the available clinical data. METHODS: In this study,
      pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991
      2004 were examined. RESULTS: A total of 334 pituitary adenomas were found in 316
      pituitaries. One hundred and thirty-two sparsely granulated prolactin cell
      adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were
      diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19
      sparsely granulated) and one adenoma composed of Crooke's cells were detected.
      Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four
      sparsely granulated, three densely granulated), one mixed GH cell-PRL cell
      adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four
      plurihormonal adenoma type II and two alpha-subunit-only adenomas were seen. Six
      adenomas remained unclassified because the tissue was not contained in all
      sections for immunohistochemistry. Seventeen pituitaries included multiple
      tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76
      adenomas (22.7%), which had a tumour size of > or = 3 mm, only three tumours were
      macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation
      of the available clinical data showed 99 cases of hypertension, 65 cases of
      diabetes mellitus, six patients with hyperthyroidism and four with
      hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were
      reported. The statistical correlations to clinical data were discussed.
      CONCLUSIONS: Adenomas in postmortem pituitaries differ from those in surgical
      series in proportion of adenoma types and biological behaviour.

PMID- 16645025
TI  - Commentary: the attainability of causal knowledge of genetic effects in complex
      human traits.

PMID- 16645026
TI  - Commentary: the analysis of variance and the social complexities of genetic
      causation.

PMID- 16645027
TI  - Commentary: heritability estimates--long past their sell-by date.

PMID- 16645028
TI  - Commentary: the analysis of variance is an analysis of causes (of a very
      circumscribed kind).

PMID- 16645029
TI  - Socioeconomic, environmental, and behavioural risk factors for leprosy in North
      east Brazil: results of a case-control study.
AB  - BACKGROUND: Brazil reports almost 80% of all leprosy cases in the Americas. This
      study aimed to identify socioeconomic, environmental, and behavioural factors
      associated with risk of leprosy occurrence in the endemic North-eastern region.
      METHODS: A case-control study in four municipalities. CASES: cases of leprosy
      diagnosed in the previous 2 years, with no other known, current, or past case of
      leprosy in the household or in the neighbourhood. CONTROLS: individuals
      presenting for reasons other than skin problems to the health unit where the case
      was diagnosed and who lived in the same municipality as the case with whom it was
      matched. For each case four controls were selected. A semi-structured
      questionnaire was used to collect demographic, socioeconomic, environmental, and
      behavioural data. A multivariate hierarchical analysis was performed according to
      a previously defined framework. RESULTS: 226 cases and 857 controls were
      examined. Low education level, ever having experienced food shortage, bathing
      weekly in open water bodies (creek, river and/or lake) 10 years previously, and a
      low frequency of changing bed linen or hammock (>or=biweekly) currently were all
      significantly associated with leprosy. Having a BCG vaccination scar was found to
      be a highly significant protective factor. CONCLUSIONS: Except for BCG
      vaccination, variables that remained significant in the hierarchical analysis are
      cultural or linked to poverty. They may act on different levels of the
      transmission of Mycobacterium leprae and/or the progress from infection to
      disease. These findings give credit to the hypothesis that person-to-person is
      not the only form of M. leprae transmission, and that indirect transmission might
      occur, and other reservoirs should exist outside the human body.

PMID- 16645031
TI  - Commentary: utilizing information on causes of neonatal deaths in less-developed
      countries.

PMID- 16645033
TI  - The analysis of variance and the analysis of causes. 1974.

PMID- 16645034
TI  - GABA controls the level of quorum-sensing signal in Agrobacterium tumefaciens.
AB  - The concentration of GABA increases rapidly in wounded plant tissues, but the
      implication of this GABA pulse for plant-bacteria interactions is not known. Here
      we reveal that GABA stimulated the inactivation of the N-(3
      oxooctanoyl)homoserine lactone (OC8-HSL) quorum-sensing signal (or "quormone") by
      the Agrobacterium lactonase AttM. GABA induced the expression of the attKLM
      operon, which was correlated to a decrease in OC8-HSL concentration in
      Agrobacterium tumefaciens cultures. The Agrobacterium GABA transporter Bra was
      required for this GABA-signaling pathway. Furthermore, transgenic tobacco plants
      with elevated GABA levels were less sensitive to A. tumefaciens C58 infection
      than were wild-type plants. These findings indicate that plant GABA may modulate
      quorum sensing in A. tumefaciens, thereby affecting its virulence on plants.
      Whereas GABA is an essential cell-to-cell signal in eukaryotes, here we provide
      evidence of GABA acting as a signal between eukaryotes and pathogenic bacteria.
      The GABA signal represents a potential target for the development of a strategy
      to control the virulence of bacterial pathogens.

PMID- 16645035
TI  - Force-dependent chemical kinetics of disulfide bond reduction observed with
      single-molecule techniques.
AB  - The mechanism by which mechanical force regulates the kinetics of a chemical
      reaction is unknown. Here, we use single-molecule force-clamp spectroscopy and
      protein engineering to study the effect of force on the kinetics of
      thiol/disulfide exchange. Reduction of disulfide bonds through the
      thiol/disulfide exchange chemical reaction is crucial in regulating protein
      function and is known to occur in mechanically stressed proteins. We apply a
      constant stretching force to single engineered disulfide bonds and measure their
      rate of reduction by DTT. Although the reduction rate is linearly dependent on
      the concentration of DTT, it is exponentially dependent on the applied force,
      increasing 10-fold over a 300-pN range. This result predicts that the disulfide
      bond lengthens by 0.34 A at the transition state of the thiol/disulfide exchange
      reaction. Our work at the single bond level directly demonstrates that
      thiol/disulfide exchange in proteins is a force-dependent chemical reaction. Our
      findings suggest that mechanical force plays a role in disulfide reduction in
      vivo, a property that has never been explored by traditional biochemistry.
      Furthermore, our work also indicates that the kinetics of any chemical reaction
      that results in bond lengthening will be force-dependent.

PMID- 16645036
TI  - Multivortex micromixing.
AB  - The ability to mix liquids in microchannel networks is fundamentally important in
      the design of nearly every miniaturized chemical and biochemical analysis system.
      Here, we show that enhanced micromixing can be achieved in topologically simple
      and easily fabricated planar 2D microchannels by simply introducing curvature and
      changes in width in a prescribed manner. This goal is accomplished by harnessing
      a synergistic combination of (i) Dean vortices that arise in the vertical plane
      of curved channels as a consequence of an interplay between inertial,
      centrifugal, and viscous effects, and (ii) expansion vortices that arise in the
      horizontal plane due to an abrupt increase in a conduit's cross-sectional area.
      We characterize these effects by using confocal microscopy of aqueous fluorescent
      dye streams and by observing binding interactions between an intercalating dye
      and double-stranded DNA. These mixing approaches are versatile and scalable and
      can be straightforwardly integrated as generic components in a variety of lab-on
      a-chip systems.

PMID- 16645037
TI  - The N-Terminal A/B domain of the thyroid hormone receptor-beta2 isoform
      influences ligand-dependent recruitment of coactivators to the ligand-binding
      domain.
AB  - Thyroid hormone receptors (TRs), expressed as TRalpha1, TRbeta1, and TRbeta2
      isoforms, are members of the steroid hormone nuclear receptor gene superfamily,
      which comprises ligand-dependent transcription factors. The TR isoforms differ
      primarily in their N-terminal (A/B) domains, suggesting that the A/B regions
      mediate distinct transcriptional activation functions in a cell type-dependent or
      promoter-specific fashion. The nuclear receptor ligand-binding domain (LBD)
      undergoes a conformational change upon ligand binding that results in the
      recruitment of coactivators to the LBD. For glucocorticoid receptor and estrogen
      receptor-alpha, the same coactivator can contact both the LBD and A/B domains,
      thus leading to enhanced transcriptional activation. Very little is known
      regarding the role of the A/B domains of the TR isoforms. The A/B domain of
      TRbeta2 exhibits higher ligand-independent transcriptional activity than the A/B
      regions of TRalpha1 or TRbeta1. Thus, we examined the role of the A/B domain and
      the LBD of rat TRbeta2 in integrating the transcriptional activation function of
      the A/B and LBD domains by different coactivators. Both domains are essential for
      a productive functional interaction with cAMP response element-binding protein
      (CREB)-binding protein (CBP), and we found that CBP binds to the A/B domain of
      TRbeta2 in vitro. In contrast, steroid receptor coactivator-1a (SRC-1a) interacts
      strongly with the LBD but not the A/B domain. The coactivator NRC (nuclear
      receptor coactivator) interacts primarily with the LBD, although a weak
      interaction with the A/B domain further enhances ligand-dependent binding with
      TRbeta2. Our studies document the interplay between the A/B domain and the LBD of
      TRbeta2 in recruiting different coactivators to the receptor. Because NRC and SRC
      1a bind CBP, and CBP enhances ligand-dependent activity, our studies suggest a
      model in which coactivator recruitment of NRC (or SRC-1a) occurs primarily
      through the LBD whereas the complex is further stabilized through an interaction
      of CBP with the N terminus of TRbeta2.

PMID- 16645038
TI  - Nature of functional estrogen receptors at the plasma membrane.
AB  - Although rapid signaling by estrogen at the plasma membrane is established, it is
      controversial as to the nature of the receptor protein. Estrogen may bind
      membrane proteins comparable to classical nuclear estrogen receptors (ERs), but
      some studies identify nonclassical receptors, such as G protein-coupled receptor
      (GPR)30. We took several approaches to define membrane-localized estrogen-binding
      proteins. In endothelial cells (ECs) from ERalpha/ERbeta combined-deleted mice,
      estradiol (E2) failed to specifically bind, and did not activate cAMP, ERK, or
      phosphatidyinositol 3-kinase or stimulate DNA synthesis. This is in contrast to
      wild-type ECs, indicating the lack of any functional estrogen-binding proteins in
      ERalpha/ERbeta combined-deleted ECs. To directly determine the identity of
      membrane and nuclear-localized ER, we isolated subcellular receptor pools from
      MCF7 cells. Putative ER proteins were trypsin digested and subjected to tandem
      array mass spectrometry. The output analysis identified membrane and nuclear E2
      binding proteins as classical human ERalpha. We also determined whether GPR30
      plays any role in E2 rapid actions. MCF7 (ER and GPR30 positive) and SKBR-3 (ER
      negative, GPR30 positive) cells were incubated with E2. Only MCF7 responded with
      significantly increased signaling. In MCF7, the response to E2 was not different
      in cells transfected with small interfering RNA to green fluorescent protein or
      GPR30. In contrast, interfering RNA to ERalpha or ER inhibition prevented rapid
      signaling and resulting biology in MCF7. In breast cancer and ECs, nuclear and
      membrane ERs are the same proteins. Furthermore, classical ERs mediate rapid
      signals induced by E2 in these cells.

PMID- 16645039
TI  - The role of the general transcription factor IIF in androgen receptor-dependent
      transcription.
AB  - The androgen receptor (AR) is a member of the steroid receptor subfamily of
      nuclear receptors and is important for normal male sexual differentiation and
      fertility. The major transactivation function of the AR, termed activation
      function 1 (AF1), is modular in structure and has been mapped to the N terminus
      of the protein. To understand better the mechanisms whereby the AR activates
      transcription, we have established a novel cell-free transcription assay. This is
      based on the use of a dual reporter gene template, containing promoter proximal
      and distal G-less cassettes, which result in different size transcripts that can
      be easily detected and quantified. The promoter proximal transcript gives an
      indication of transcription initiation and promoter escape, whereas the relative
      levels of the distal transcript indicate elongation efficiency. The AR-AF1-Lex
      protein enhanced production of both transcripts whereas, in the absence of DNA
      binding, the AF1 domain squelched both initiation and elongation. Mutations in
      the transactivation domain that impaired transactivation and/or binding of the
      general transcription factor IIF (TFIIF) were found to reduce the ability of AR
      AF1 to squelch transcription. Addition of recombinant TFIIF reversed squelching
      of the promoter-proximal but not the -distal G-less transcript, whereas addition
      of TATA-binding protein failed to reverse squelching of either transcript. Taken
      together, these results demonstrate that the AR N-terminal transactivation
      function, AF1, has the potential to regulate transcription at both the level of
      initiation and elongation, and that interactions with TFIIF are important during
      preinitiation complex assembly/open complex formation and/or promoter escape.

PMID- 16645040
TI  - Dependence of electrical activity and calcium influx-controlled prolactin release
      on adenylyl cyclase signaling pathway in pituitary lactotrophs.
AB  - Pituitary lactotrophs in vitro fire extracellular Ca2+-dependent action
      potentials spontaneously through still unidentified pacemaking channels, and the
      associated voltage-gated Ca2+influx (VGCI) is sufficient to maintain basal
      prolactin (PRL) secretion high and steady. Numerous plasma membrane channels have
      been characterized in these cells, but the mechanism underlying their pacemaking
      activity is still not known. Here we studied the relevance of cyclic nucleotide
      signaling pathways in control of pacemaking, VGCI, and PRL release. In mixed
      anterior pituitary cells, both VGCI-inhibitable and -insensitive adenylyl cyclase
      (AC) subtypes contributed to the basal cAMP production, and soluble guanylyl
      cyclase was exclusively responsible for basal cGMP production. Inhibition of
      basal AC activity, but not soluble guanylyl cyclase activity, reduced PRL
      release. In contrast, forskolin stimulated cAMP and cGMP production as well as
      pacemaking, VGCI, and PRL secretion. Elevation in cAMP and cGMP levels by
      inhibition of phosphodiesterase activity was also accompanied with increased PRL
      release. The AC inhibitors attenuated forskolin-stimulated cyclic nucleotide
      production, VGCI, and PRL release. The cell-permeable 8-bromo-cAMP stimulated
      firing of action potentials and PRL release and rescued hormone secretion in
      cells with inhibited ACs in an extracellular Ca2+-dependent manner, whereas 8
      bromo-cGMP and 8-(4-chlorophenylthio)-2'-O-methyl-cAMP were ineffective. Protein
      kinase A inhibitors did not stop spontaneous and forskolin-stimulated pacemaking,
      VGCI, and PRL release. These results indicate that cAMP facilitates pacemaking,
      VGCI, and PRL release in lactotrophs predominantly in a protein kinase A- and
      Epac cAMP receptor-independent manner.

PMID- 16645041
TI  - Identification of a basic helix-loop-helix transcription factor expressed in
      mammary gland alveolar cells and required for maintenance of the differentiated
      state.
AB  - The development of mammary glands relies on complicated signaling pathways that
      control cell proliferation, differentiation, and apoptotic events through
      transcriptional regulatory circuits. A key family of transcription factors used
      in mammary gland development is the helix-loop-helix/basic helix-loop-helix
      (HLH/bHLH) protein family. In this study, we identify Mist1 as a tissue
      restricted Class II bHLH transcription factor expressed in lactating mammary
      glands. Mouse and human mammary glands accumulated Mist1 protein exclusively in
      secretory alveolar cells, and Mist1 transcripts were differentially expressed in
      mouse SCp2 cells induced to differentiate by addition of lactogenic hormones.
      Mist1 null (Mist1(KO)) lactating mammary glands were defective in normal
      lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen
      and premature activation of the signal transducer and activator of transcription
      3 signaling pathway. These cells also failed to maintain expression of the gap
      junction proteins connexin26 and connexin32, leading to the loss of gap
      junctions. Our findings suggest that loss of Mist1 impairs the maintenance of the
      fully differentiated alveolar state and, for the first time, places Mist1 within
      the hierarchy of known HLH/bHLH proteins that control mammary epithelial cell
      development.

PMID- 16645042
TI  - Ligand-controlled interaction of histone acetyltransferase binding to ORC-1
      (HBO1) with the N-terminal transactivating domain of progesterone receptor
      induces steroid receptor coactivator 1-dependent coactivation of transcription.
AB  - Modulators of cofactor recruitment by nuclear receptors are expected to play an
      important role in the coordination of hormone-induced transactivation processes.
      To identify such factors interacting with the N-terminal domain (NTD) of the
      progesterone receptor (PR), we used this domain as bait in the yeast Sos-Ras two
      hybrid system. cDNAs encoding the C-terminal MYST (MOZ-Ybf2/Sas3-Sas2-Tip60
      acetyltransferases) domain of HBO1 [histone acetyltransferase binding to the
      origin recognition complex (ORC) 1 subunit], a member of the MYST acetylase
      family, were thus selected from a human testis cDNA library. In transiently
      transfected CV1 cells, the wild-type HBO1 [611 amino acids (aa)] enhanced
      transcription mediated by steroid receptors, notably PR, mineralocorticoid
      receptor, and glucocorticoid receptor, and strongly induced PR and estrogen
      receptor coactivation by steroid receptor coactivator 1a (SRC-1a). As assessed by
      two-hybrid and glutathione-S-transferase pull-down assays, the HBO1 MYST
      acetylase domain (aa 340-611) interacts mainly with the NTD, and also contacts
      the DNA-binding domain and the hinge domains of hormone-bound PR. The HBO1 N
      terminal region (aa 1-340) associates additionally with PR ligand-binding domain
      (LBD). HBO1 was found also to interact through its NTD with SRC-1a in the absence
      of steroid receptor. The latter coassociation enhanced specifically activation
      function 2 activation function encompassed in the LBD. Conversely, the MYST
      acetylase domain specifically enhanced SRC-1 coupling with PR NTD, through a
      hormone-dependent mechanism. In human embryonic kidney 293 cells expressing human
      PRA or PRB, HBO1 raised selectively an SRC-1-dependent response of PRB but failed
      to regulate PRA activity. We show that HBO1 acts through modification of an LBD
      controlled structure present in the N terminus of PRB leading to the modulation
      of SRC-1 functional coupling with activation function 3-mediated transcription.
      Importantly, real-time RT-PCR analysis also revealed that HBO1 enhanced SRC-1
      coactivation of PR-dependent transcription of human endogenous genes such as
      alpha-6 integrin and 11beta-hydroxydehydrogenase 2 but not that of amphiregulin.
      Immunofluorescence and confocal microscopy of human embryonic kidney-PRB cells
      demonstrated that the hormone induces the colocalization of HBO1 with PR-SRC-1
      complex into nuclear speckles characteristic of PR-mediated chromatin remodeling.
      Our results suggest that HBO1 might play an important physiological role in human
      PR signaling.

PMID- 16645043
TI  - Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose
      overexpression leads to estrogen-independent growth of human breast cancer cells.
AB  - Estrogen receptor (ER)alpha activity is controlled by the balance of coactivators
      and corepressors contained within cells that are recruited into transcriptional
      complexes. The metastasis-associated protein (MTA) family has been demonstrated
      to be associated with breast tumor cell progression and ERalpha activity. We
      demonstrate that MTA2 expression is correlated with ERalpha protein expression in
      invasive breast tumors. We show that the MTA2 family member can bind to ERalpha
      and repress its activity in human breast cancer cells. Furthermore, it can
      inhibit ERalpha-mediated colony formation and render breast cancer cells
      resistant to estradiol and the growth-inhibitory effects of the antiestrogen
      tamoxifen. MTA2 participates in the deacetylation of ERalpha protein, potentially
      through its associated histone deacetylase complex 1 activity. We hypothesize
      that MTA2 is a repressor of ERalpha activity and that it could represent a new
      therapeutic target of ERalpha action in human breast tumors.

PMID- 16645044
TI  - Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of
      APP and Notch by HIF-1 and hypoxia.
AB  - The proteolytic cleavage of Alzheimer beta-amyloid precursor protein (APP) and
      signaling receptor Notch is mediated by the PS/gamma-secretase complex, which
      consists of presenilins, nicastrin, APH-1, and PEN-2. Although the four
      components are known to coordinately regulate each other at the protein level,
      information regarding their transcription regulation is scarce. Here we
      characterized the 5'-flanking region of the human APH-1A gene and identified a
      271-bp fragment containing the transcription initiation site for the promoter
      activity. Sequence analysis, mutagenesis, and gel shift studies revealed a
      binding of AP4 and HIF-1 to the promoter, which affects the promoter activity.
      Activation of HIF-1 by short-term NiCl2 treatments (a condition of chemical
      hypoxia) dramatically increased APH-1A mRNA and protein expression, accompanied
      by increased secretion of Abeta and decreased APP CTFs formation, indicative of
      an increase in gamma-secretase activity. NiCl2 treatments had little effect on
      APP and the other three components of the gamma-secretase complex. The cellular
      concentration of Notch intracellular domain (NICD) was also increased by the
      hypoxic treatment. Our results demonstrate that APH-1A expression and the gamma
      secretase mediated Abeta and Notch NICD generation are regulated by HIF-1, and
      the specific control of APH-1A expression may imply physiological functions
      uniquely assigned to APH-1A.

PMID- 16645045
TI  - Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to
      microtubules.
AB  - Neurofibrillary tangles (NFTs), consisting of abnormally hyperphosphorylated tau,
      are implicated in the pathogenesis of several neurodegenerative diseases
      including Alzheimer's disease (AD). The molecular mechanisms underlying the
      regulation of tau phosphorylation are largely unknown. While the PI3K/Akt pathway
      has been shown to regulate multiple cellular events pertinent to AD pathogenesis,
      potential functions of tumor suppressor phosphatase and tensin homologue deleted
      on chromosome 10 (PTEN) in AD pathogenesis have not been explored. Here, we
      examine the effects of PTEN on tau phosphorylation, its microtubule association
      and formation of aggregates, and consequentially neuronal morphology. In cultured
      cells, overexpression of wild-type (WT) PTEN alters tau phosphorylation at
      several sites, increases tau-microtubule association and decreases formation of
      tau aggregates. In addition, the phosphatase-null PTEN increases tau aggregation
      and impairs tau binding to microtubule and neurite outgrowth of neurons
      expressing the mutant PTEN. We also found a significant loss of PTEN in AD
      patient brains correlated with a dramatically increased concentration of phospho
      tau at Ser-214 in NFTs. Together, our results demonstrate that PTEN regulates tau
      phosphorylation, binding to microtubules and formation of aggregates and neurite
      outgrowth. These findings suggest a link between malfunction of PTEN and
      tauopathy, and imply PTEN as a therapeutic target for tauopathy.

PMID- 16645046
TI  - Presenilin/gamma-secretase activity regulates protein clearance from the
      endocytic recycling compartment.
AB  - The presenilin (PS)/gamma-secretase complex proteolytically cleaves more than 20
      different proteins in addition to the amyloid precursor protein (APP). These
      substrates are almost exclusively type I membrane proteins. Many undergo
      internalization from the cell surface followed by degradation or recycling back
      to the plasma membrane through the endocytic recycling compartment (ERC).
      Evidence shows that the PSs also regulate intracellular trafficking of APP and
      its C-terminal fragments (CTFs). To investigate whether PS/gamma-secretase
      activity is required for normal endosomal recycling, we performed live cell
      imaging experiments with fluorescently labeled transferrin, reported to
      specifically traffic through the ERC. By using pharmacological gamma-secretase
      inhibitors or cell lines lacking functional PS/gamma-secretase, here we show that
      PS/gamma-secretase activity is required for clearance of transferrin from the
      ERC. Interestingly, lack of PS/gamma-secretase function also resulted in the
      accumulation of APP and APP-CTFs in the ERC in addition to the cell surface.
      Familial Alzheimer's disease mutations in APP-CTFs did not affect endocytic
      recycling of these proteins. Our results suggest that PS/gamma-secretase activity
      is required for normal endosomal recycling of soluble and membrane-associated
      proteins through the ERC and propose a new mechanism by which impaired PS/gamma
      secretase function may eventually contribute to neurodegeneration.

PMID- 16645047
TI  - Isoelectric points and post-translational modifications of connexin26 and
      connexin32.
AB  - The isoelectric points of the gap junction proteins connexin26 (Cx26) and
      connexin32 (Cx32) were determined by isoelectric focusing in free fluids. The
      isoelectric points were significantly more acidic than predicted from amino acid
      sequences and different from each other, allowing homomeric channels to be
      resolved separately. The isoelectric points of the homomeric channels bracketed
      the isoelectric points of heteromeric Cx26/Cx32 channels. For heteromeric
      channels, Cx26 and Cx32 were found in overlapping, pH-focused fractions,
      indicating quaternary structure was retained. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry was used to identify post
      translational modifications of Cx26 and Cx32 cytoplasmic domains, including the
      first reported post-translational modifications of Cx26. Suspected modifications
      were hydroxylation and/or phosphorylation near the amino terminus of both
      connexins, gamma-carboxyglutamate residues in the cytoplasmic loop of both
      connexins, phosphorylation in the carboxyl-terminal domain of Cx32, and
      palmitoylation at the carboxyl-terminus of Cx32. These modifications contribute
      to the measured acidic isoelectric points of Cx26 and Cx32, whereas their low
      molecular masses would not appreciably change connexin SDS-PAGE mobility. Most of
      these modifications have not previously been identified for connexins and may be
      instrumental in guiding and understanding novel aspects of channel trafficking
      and molecular mechanisms of channel regulation.

PMID- 16645048
TI  - Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts.
AB  - Ceramide is a key lipid molecule necessary to regulate some cellular processes,
      including apoptosis and cell differentiation. In this context, its production has
      been shown to occur via sphingomyelin hydrolysis or sphingosine acylation. Here,
      we show that in human fibroblasts, plasma membrane ceramide is also produced from
      ganglioside GM3 by detachment of sugar units. Membrane-bound glycosylhydrolases
      have a role in this process. In fact, the production of ceramide from GM3 has
      been observed even under experimental conditions able to block endocytosis or
      lysosomal activity, and the overexpression of the plasma membrane ganglioside
      sialidase Neu3 corresponded to a higher production of ceramide in the plasma
      membrane. The increased activity of Neu3 was paralleled by an increase of GM3
      synthase mRNA and GM3 synthase activity. Neu3-overexpressing fibroblasts were
      characterized by a reduced proliferation rate and higher basal number of
      apoptotic cells in comparison with wild-type cells. A similar behavior was
      observed when normal fibroblasts were treated with exogenous C2-ceramide.

PMID- 16645049
TI  - CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.
AB  - Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC)
      channels following Ca2+ release from intracellular stores. We performed a genome
      wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that
      inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified
      CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC
      currents. We characterized the human ortholog of CRACM1, a plasma membrane
      resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did
      not affect CRAC currents, RNAi-mediated knockdown disrupted its activation.
      CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the
      CRAC signaling machinery.

PMID- 16645050
TI  - Emergent properties of reduced-genome Escherichia coli.
AB  - With the use of synthetic biology, we reduced the Escherichia coli K-12 genome by
      making planned, precise deletions. The multiple-deletion series (MDS) strains,
      with genome reductions up to 15%, were designed by identifying nonessential genes
      and sequences for elimination, including recombinogenic or mobile DNA and cryptic
      virulence genes, while preserving good growth profiles and protein production.
      Genome reduction also led to unanticipated beneficial properties: high
      electroporation efficiency and accurate propagation of recombinant genes and
      plasmids that were unstable in other strains. Eradication of stress-induced
      transposition evidently stabilized the MDS genomes and provided some of the new
      properties.

PMID- 16645051
TI  - Lamin A-dependent nuclear defects in human aging.
AB  - Mutations in the nuclear structural protein lamin A cause the premature aging
      syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in
      normal aging is unknown. We show that the same molecular mechanism responsible
      for HGPS is active in healthy cells. Cell nuclei from old individuals acquire
      defects similar to those of HGPS patient cells, including changes in histone
      modifications and increased DNA damage. Age-related nuclear defects are caused by
      sporadic use, in healthy individuals, of the same cryptic splice site in lamin A
      whose constitutive activation causes HGPS. Inhibition of this splice site
      reverses the nuclear defects associated with aging. These observations implicate
      lamin A in physiological aging.

PMID- 16645052
TI  - Wnt gradient formation requires retromer function in Wnt-producing cells.
AB  - Wnt proteins function as morphogens that can form long-range concentration
      gradients to pattern developing tissues. Here, we show that the retromer, a
      multiprotein complex involved in intracellular protein trafficking, is required
      for long-range signaling of the Caenorhabditis elegans Wnt ortholog EGL-20. The
      retromer functions in EGL-20-producing cells to allow the formation of an EGL-20
      gradient along the anteroposterior axis. This function is evolutionarily
      conserved, because Wnt target gene expression is also impaired in the absence of
      the retromer complex in vertebrates. These results demonstrate that the ability
      of Wnt to regulate long-range patterning events is dependent on a critical and
      conserved function of the retromer complex within Wnt-producing cells.

PMID- 16645053
TI  - Re-aim blame for NIH's hard times.

PMID- 16645054
TI  - Archaeology. New carbon dates support revised history of ancient Mediterranean.

PMID- 16645055
TI  - Stem cells. Court rules in favor of California stem cell institute.

PMID- 16645057
TI  - Planetary science. Simulation suggests peaceful origin for giant planet's weird
      spin.

PMID- 16645056
TI  - Scientific community. University clears Chinese biophysicist of misconduct.

PMID- 16645058
TI  - France. Chemist claims innocence to spying charge.

PMID- 16645059
TI  - Oceanography. Korea and Japan clash over surveys.

PMID- 16645060
TI  - Genetics. Parasite-resistant mosquitoes: a natural weapon against malaria?

PMID- 16645061
TI  - Biomedical research. Bone disease gene finally found.

PMID- 16645062
TI  - Microbiology. Environmentally sensitive protein proves key to making yeast
      pathogenic.

PMID- 16645063
TI  - Cell biology. Picking up the pieces after Hwang.

PMID- 16645064
TI  - Biomedical research. Fragile X's unwelcome relative.

PMID- 16645065
TI  - Biomedical research. A fix for fragile X syndrome?

PMID- 16645066
TI  - Alice Dautry profile. After the storm, new Pasteur chief treads softly.

PMID- 16645067
TI  - Agriculture. New disease endangers Florida's already-suffering citrus trees.

PMID- 16645074
TI  - Ongoing threats to endemic species.

PMID- 16645075
TI  - A scientific supercourse.

PMID- 16645076
TI  - Marine parks need sharks?

PMID- 16645077
TI  - A not-so-abrupt departure.

PMID- 16645078
TI  - Mechanisms for resistance in soil.

PMID- 16645079
TI  - Comment on "Reconstructing past climate from noisy data".
AB  - von Storch et al. (Reports, 22 October 2004, p. 679) criticized the ability of
      the "hockey stick" climate field reconstruction method to yield realistic
      estimates of past variation in Northern Hemisphere temperature. However, their
      conclusion was based on incorrect implementation of the reconstruction procedure.
      Calibration was performed using detrended data, thus artificially removing a
      large fraction of the physical response to radiative forcing.

PMID- 16645080
TI  - Computer simulations. Technological advances in inquiry learning.

PMID- 16645081
TI  - Biophysics. Lonely voltage sensor seeks protons for permeation.

PMID- 16645082
TI  - Planetary science. Ice among the rocks.

PMID- 16645083
TI  - Atmosphere. Plant respiration in a warmer world.

PMID- 16645084
TI  - Evolution. Size does not matter for mitochondrial DNA.

PMID- 16645085
TI  - Astronomy. Pulsar magnetospheres and pulsar death.

PMID- 16645086
TI  - Neuroscience. A neuronal receptor for botulinum toxin.

PMID- 16645087
TI  - Reefs of the deep: the biology and geology of cold-water coral ecosystems.
AB  - Coral reefs are generally associated with shallow tropical seas; however, recent
      deep-ocean exploration using advanced acoustics and submersibles has revealed
      unexpectedly widespread and diverse coral ecosystems in deep waters on
      continental shelves, slopes, seamounts, and ridge systems around the world.
      Advances reviewed here include the use of corals as paleoclimatic archives and
      their biogeological functioning, biodiversity, and biogeography. Threats to these
      fragile, long-lived, and rich ecosystems are mounting: The impacts of deep-water
      trawling are already widespread, and effects of ocean acidification are
      potentially devastating.

PMID- 16645088
TI  - Santorini eruption radiocarbon dated to 1627-1600 B.C.
AB  - Precise and direct dating of the Minoan eruption of Santorini (Thera) in Greece,
      a global Bronze Age time marker, has been made possible by the unique find of an
      olive tree, buried alive in life position by the tephra (pumice and ashes) on
      Santorini. We applied so-called radiocarbon wiggle-matching to a carbon-14
      sequence of tree-ring segments to constrain the eruption date to the range 1627
      1600 B.C. with 95.4% probability. Our result is in the range of previous, less
      precise, and less direct results of several scientific dating methods, but it is
      a century earlier than the date derived from traditional Egyptian chronologies.

PMID- 16645089
TI  - Optical spectroscopy of individual single-walled carbon nanotubes of defined
      chiral structure.
AB  - We simultaneously determined the physical structure and optical transition
      energies of individual single-walled carbon nanotubes by combining electron
      diffraction with Rayleigh scattering spectroscopy. These results test fundamental
      features of the excited electronic states of carbon nanotubes. We directly
      verified the systematic changes in transition energies of semiconducting
      nanotubes as a function of their chirality and observed predicted energy
      splittings of optical transitions in metallic nanotubes.

PMID- 16645090
TI  - Biologically inspired artificial compound eyes.
AB  - This work presents the fabrication of biologically inspired artificial compound
      eyes. The artificial ommatidium, like that of an insect's compound eyes, consists
      of a refractive polymer microlens, a light-guiding polymer cone, and a self
      aligned waveguide to collect light with a small angular acceptance. The ommatidia
      are omnidirectionally arranged along a hemispherical polymer dome such that they
      provide a wide field of view similar to that of a natural compound eye. The
      spherical configuration of the microlenses is accomplished by reconfigurable
      microtemplating, that is, polymer replication using the deformed elastomer
      membrane with microlens patterns. The formation of polymer waveguides self
      aligned with microlenses is also realized by a self-writing process in a
      photosensitive polymer resin. The angular acceptance is directly measured by
      three-dimensional optical sectioning with a confocal microscope, and the detailed
      optical characteristics are studied in comparison with a natural compound eye.

PMID- 16645091
TI  - Iron-rich post-perovskite and the origin of ultralow-velocity zones.
AB  - The boundary layer between the crystalline silicate lower mantle and the liquid
      iron core contains regions with ultralow seismic velocities. Such low
      compressional and shear wave velocities and high Poisson's ratio are also
      observed experimentally in post-perovskite silicate phase containing up to 40
      mol% FeSiO3 endmember. The iron-rich post-perovskite silicate is stable at the
      pressure-temperature and chemical environment of the core-mantle boundary and can
      be formed by core-mantle reaction. Mantle dynamics may lead to further
      accumulation of this material into the ultralow-velocity patches that are
      observable by seismology.

PMID- 16645092
TI  - Chronology for the Aegean Late Bronze Age 1700-1400 B.C.
AB  - Radiocarbon (carbon-14) data from the Aegean Bronze Age 1700-1400 B.C. show that
      the Santorini (Thera) eruption must have occurred in the late 17th century B.C.
      By using carbon-14 dates from the surrounding region, cultural phases, and
      Bayesian statistical analysis, we established a chronology for the initial Aegean
      Late Bronze Age cultural phases (Late Minoan IA, IB, and II). This chronology
      contrasts with conventional archaeological dates and cultural synthesis:
      stretching out the Late Minoan IA, IB, and II phases by approximately 100 years
      and requiring reassessment of standard interpretations of associations between
      the Egyptian and Near Eastern historical dates and phases and those in the Aegean
      and Cyprus in the mid-second millennium B.C.

PMID- 16645093
TI  - Population size does not influence mitochondrial genetic diversity in animals.
AB  - Within-species genetic diversity is thought to reflect population size, history,
      ecology, and ability to adapt. Using a comprehensive collection of polymorphism
      data sets covering approximately 3000 animal species, we show that the widely
      used mitochondrial DNA (mtDNA) marker does not reflect species abundance or
      ecology: mtDNA diversity is not higher in invertebrates than in vertebrates, in
      marine than in terrestrial species, or in small than in large organisms. Nuclear
      loci, in contrast, fit these intuitive expectations. The unexpected mitochondrial
      diversity distribution is explained by recurrent adaptive evolution, challenging
      the neutral theory of molecular evolution and questioning the relevance of mtDNA
      in biodiversity and conservation studies.

PMID- 16645094
TI  - Proapoptotic BAX and BAK modulate the unfolded protein response by a direct
      interaction with IRE1alpha.
AB  - Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an
      adaptive stress response-termed the unfolded protein response (UPR)-mediated by
      the ER transmembrane protein kinase and endoribonuclease inositol-requiring
      enzyme-1alpha (IRE1alpha). We investigated UPR signaling events in mice in the
      absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout
      (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the
      liver, with extensive tissue damage and decreased expression of the IRE1
      substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells
      showed deficient IRE1alpha signaling. BAX and BAK formed a protein complex with
      the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation.
      Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and
      to provide a physical link between members of the core apoptotic pathway and the
      UPR.

PMID- 16645095
TI  - Natural malaria infection in Anopheles gambiae is regulated by a single genomic
      control region.
AB  - We surveyed an Anopheles gambiae population in a West African malaria
      transmission zone for naturally occurring genetic loci that control mosquito
      infection with the human malaria parasite, Plasmodium falciparum. The strongest
      Plasmodium resistance loci cluster in a small region of chromosome 2L and each
      locus explains at least 89% of parasite-free mosquitoes in independent pedigrees.
      Together, the clustered loci form a genomic Plasmodium-resistance island that
      explains most of the genetic variation for malaria parasite infection of
      mosquitoes in nature. Among the candidate genes in this chromosome region, RNA
      interference knockdown assays confirm a role in Plasmodium resistance for
      Anopheles Plasmodium-responsive leucine-rich repeat 1 (APL1), encoding a leucine
      rich repeat protein that is similar to molecules involved in natural pathogen
      resistance mechanisms in plants and mammals.

PMID- 16645096
TI  - Autophagic fungal cell death is necessary for infection by the rice blast fungus.
AB  - Rice blast is caused by the fungus Magnaporthe grisea, which elaborates
      specialized infection cells called appressoria to penetrate the tough outer
      cuticle of the rice plant Oryza sativa. We found that the formation of an
      appressorium required, sequentially, the completion of mitosis, nuclear
      migration, and death of the conidium (fungal spore) from which the infection
      originated. Genetic intervention during mitosis prevented both appressorium
      development and conidium death. Impairment of autophagy, by the targeted mutation
      of the MgATG8 gene, arrested conidial cell death but rendered the fungus
      nonpathogenic. Thus, the initiation of rice blast requires autophagic cell death
      of the conidium.

PMID- 16645097
TI  - Global control of dimorphism and virulence in fungi.
AB  - Microbial pathogens that normally inhabit our environment can adapt to thrive
      inside mammalian hosts. There are six dimorphic fungi that cause disease
      worldwide, which switch from nonpathogenic molds in soil to pathogenic yeast
      after spores are inhaled and exposed to elevated temperature. Mechanisms that
      regulate this switch remain obscure. We show that a hybrid histidine kinase
      senses host signals and triggers the transition from mold to yeast. The kinase
      also regulates cell-wall integrity, sporulation, and expression of virulence
      genes in vivo. This global regulator shapes how dimorphic fungal pathogens adapt
      to the mammalian host, which has broad implications for treating and preventing
      systemic fungal disease.

PMID- 16645099
TI  - Arthroplasty of the shoulder.

PMID- 16645100
TI  - Incidence and aetiology of anterior knee pain after intramedullary nailing of the
      femur and tibia.

PMID- 16645101
TI  - Assessment of reproducibility and accuracy in templating hybrid total hip
      arthroplasty using digital radiographs.
AB  - In 20 patients undergoing hybrid total hip arthroplasty, the reproducibility and
      accuracy of templating using digital radiographs were assessed. Digital images
      were manipulated using either a ten-pence coin as a marker to scale for
      magnification, or two digital-line methods using computer software. On-screen
      images were templated with standard acetate templates and compared with
      templating performed on hard-copy digital prints. The digital-line methods were
      the least reliable and accuracy of sizing compared with the inserted prostheses
      varied between -1.6% and +10.2%. The hard-copy radiographs showed better
      reproducibility than the ten-pence coin method, but were less accurate with 3.7%
      undersizing. The ten-pence coin method was the most accurate, with no significant
      differences for offset or acetabulum, and undersizing of only 0.9%. On-screen
      templating of digital radiographs with standard acetate templates is accurate and
      reproducible if a radiopaque marker such as a ten-pence coin is included when the
      original radiograph is taken.

PMID- 16645102
TI  - Acetabular revision with morsellised allogenic bone graft and a cemented metal
      backed component.
AB  - Failure of total hip arthroplasty with acetabular deficiency occurred in 55
      patients (60 hips) and was treated with acetabular revision using morsellised
      allograft and a cemented metal-backed component. A total of 50 patients (55 hips)
      were available for clinical and radiological evaluation at a mean follow-up of
      5.8 years (3 to 9.5). No hip required further revision of the acetabular
      component because of aseptic loosening. All the hips except one had complete
      incorporation of the allograft demonstrated on the radiographs. A complete
      radiolucent line of > 1 mm was noted in two hips post-operatively. A good to
      excellent result occurred in 50 hips (91%). With radiological evidence of aseptic
      loosening of the acetabular component as the end-point, the survivorship at a
      mean of 5.8 years after surgery was 96.4%. The use of impacted allograft chips in
      combination with a cemented metal-backed acetabular component and screw fixation
      can achieve good medium-term results in patients with acetabular bone deficiency.

PMID- 16645103
TI  - Treatment of the young active patient with osteoarthritis of the hip. A five- to
      seven-year comparison of hybrid total hip arthroplasty and metal-on-metal
      resurfacing.
AB  - We compared the five- to seven-year clinical and radiological results of the
      metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in
      two groups of 54 hips, matched for gender, age, body mass index and activity
      level. Function was excellent in both groups, as measured by the Oxford hip
      score, but the Birmingham hip resurfacings had higher University of California at
      Los Angeles activity scores and better EuroQol quality of life scores. The total
      hip arthroplasties had a revision or intention-to-revise rate of 8%, and the
      Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on
      surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear
      and osteolysis under observation, and 8% of Birmingham hip resurfacings showed
      migration of the femoral component. Polyethylene wear was present in 48% of the
      hybrid hips without osteolysis. Of the femoral components in the Birmingham hip
      resurfacing group which had not migrated, 66% had radiological changes of unknown
      significance.

PMID- 16645104
TI  - Accuracy of a computer-assisted navigation system for total knee replacement.
AB  - The object of this study was to develop a method to assess the accuracy of an
      image-free total knee replacement navigation system in legs with normal or
      abnormal mechanical axes. A phantom leg was constructed with simulated hip and
      knee joints and provided a means to locate the centre of the ankle joint.
      Additional joints located at the midshaft of the tibia and femur allowed
      deformation in the flexion/extension, varus/valgus and rotational planes. Using a
      digital caliper unit to measure the coordinates precisely, a software program was
      developed to convert these local coordinates into a determination of actual leg
      alignment. At specific points in the procedure, information was compared between
      the digital caliper measurements and the image-free navigation system. Repeated
      serial measurements were undertaken. In the setting of normal alignment the mean
      error of the system was within 0.5 degrees . In the setting of abnormal plane
      alignment in both the femur and the tibia, the error was within 1 degrees . This
      is the first study designed to assess the accuracy of a clinically-validated
      navigation system. It demonstrates in vitro accuracy of the image-free navigation
      system in both normal and abnormal leg alignment settings.

PMID- 16645105
TI  - Peri-prosthetic bone mineral density after total knee arthroplasty. Cemented
      versus cementless fixation.
AB  - We compared peri-prosthetic bone mineral density between identical cemented and
      cementless LCS rotating platform total knee arthroplasties. Two matched cohorts
      had dual energy x-ray absorptiometry scans two years post-operatively using a
      modified validated densitometric analysis protocol, to assess peri-prosthetic
      bone mineral density. The knee that was not operated on was also scanned to
      enable the calculation of a relative bone mineral density difference. Oxford Knee
      and American Knee Society scores were comparable in the two cohorts. Statistical
      analysis revealed no significant difference in absolute, or relative peri
      prosthetic bone mineral density with respect to the method of fixation. However,
      the femoral peri-prosthetic bone mineral density and relative bone mineral
      density difference were significantly decreased, irrespective of the method of
      fixation, particularly in the anterior distal portion of the femur, with a mean
      reduction in relative bone mineral density difference of 27%. There was no
      difference in clinical outcome between the cemented and cementless LCS total knee
      arthroplasty. However, both produce stress-shielding around the femoral implants.
      This leads us to question the use of more expensive cementless total knee
      components.

PMID- 16645106
TI  - Outcome of osteochondral autograft transplantation for type-V cystic
      osteochondral lesions of the talus.
AB  - The treatment of osteochondral lesions of the talus has evolved with the
      development of improved imaging and arthroscopic techniques. However, the outcome
      of treatment for large cystic type-V lesions is poor, using conventional
      grafting, debridement or microfracture techniques. This retrospective study
      examined the outcomes of 50 patients with a cystic talar defect who were treated
      with arthroscopically harvested, cored osteochondral graft taken from the
      ipsilateral knee. Of the 50 patients, 45 (90%) had a mean good to excellent score
      of 80.3 (52 to 90) in the Karlsson-Peterson Ankle Score, at a mean follow-up of
      36 months (24 to 83). A malleolar osteotomy for exposure was needed in 26
      patients and there were no malleolar mal- or nonunions. One patient had symptoms
      at the donor site three months after surgery; these resolved after arthroscopic
      release of scar tissue. This technique is demanding with or without a malleolar
      osteotomy, but if properly performed has a high likelihood of success.

PMID- 16645107
TI  - Electromyographic comparison of various exercises to improve elbow flexion
      following intercostal nerve transfer.
AB  - We compared the quantitative electromyographic activity of the elbow flexors
      during four exercises (forced inspiration, forced expiration, trunk flexion and
      attempted elbow flexion), following intercostal nerve transfer to the
      musculocutaneous nerve in 32 patients who had sustained root avulsion brachial
      plexus injuries. Quantitative electromyographic evaluation of the mean and
      maximum amplitude was repeated three times for each exercise. We found that mean
      and maximum elbow flexor activity was highest during trunk flexion, followed by
      attempted elbow flexion, forced inspiration and finally forced expiration. The
      difference between each group was significant (p < 0.001), with the exception of
      the difference between trunk flexion and attempted elbow flexion. Consequently,
      we recommend trunk flexion exercises to aid rehabilitation following intercostal
      nerve transfer.

PMID- 16645108
TI  - Arthroplasty for advanced Kienbock's disease using a radial bone flap with a
      vascularised wrapping of pronator quadratus.
AB  - We have performed a form of lunate replacement arthroplasty, which included
      excision of the lunate and insertion of a vascularised radial bone flap wrapped
      in pronator quadratus, for stage IIIB or stage IV Kienbock's disease, in 41
      patients who have been followed up for more than three years. All patients
      reported an improvement in their symptoms, and 20 of the 41 became free of pain
      after the operation. Extension and flexion of the wrist were increased by a mean
      of 9 degrees and 6 degrees , respectively (p < 0.05). The radioscaphoid angle and
      the carpal height ratio were not significantly changed and only minimal
      deterioration was observed due to degenerative change. The size, density or
      location of the inserted bone did not change with time. A vascularised radial
      bone flap wrapped in pronator quadratus can be a reliable treatment option for
      advanced Kienbock's disease, when the pedicled bone and muscle envelope acts as a
      stable spacer for the excised lunate.

PMID- 16645109
TI  - Percutaneous vertebroplasty for vertebral compression fractures with and without
      intravertebral clefts.
AB  - We present the clinical and radiological results of percutaneous vertebroplasty
      in the treatment of 58 vertebral compression fractures in 51 patients at a
      minimum follow-up of two years. Group 1 consisted of 39 patients, in whom there
      was no associated intravertebral cleft, whilst group 2 comprised 12 patients with
      an intravertebral cleft. The Oswestry disability index (ODI) and visual analogue
      scale (VAS) scores were recorded prospectively. The radiological evidence of
      kyphotic deformity, vertebral height, leakage of cement and bone resorption
      around the cement were studied retrospectively, both before and after operation
      and at the final follow-up. The ODI and VAS scores in both groups decreased after
      treatment, but the mean score in group 2 was higher than that in group 1 (p =
      0.02 (ODI), p = 0.02 (VAS)). There was a greater initial correction of the
      kyphosis in group 2 than in group 1, although the difference was not
      statistically significant. However, loss of correction was greater in group 2.
      Leakage of cement was seen in 24 (41.4%) of 58 vertebrae (group 1, 32.6% (15 of
      46); group 2, 75% (9 of 12)), mainly of type B through the basal vertebral vein
      in group 1 and of type C through the cortical defect in group 2. Resorption of
      bone around the cement was seen in three vertebrae in group 2 and in one in group
      1. There were seven adjacent vertebral fractures in group 1 and one in group 2.
      Percutaneous vertebroplasty is an effective treatment for osteoporotic
      compression fractures with or without an intravertebral cleft. Nonetheless,
      higher rates of complications related to the cement must be recognised in
      patients in the presence of an intravertebral cleft.

PMID- 16645110
TI  - Familial chordoma. A report of two cases.
AB  - We have treated 175 patients with a chordoma over a ten-year period. Only two had
      a family history of the condition and we describe these in this paper. In one
      patient the tumour was at the craniocervical junction and in the other the lesion
      affected the sacrum. We have undertaken a literature review of familial chordoma
      and have identified chromosomal abnormalities associated with the condition.

PMID- 16645111
TI  - Combined injuries of the brachial plexus and spinal cord.
AB  - A total of 11 patients with combined traumatic injuries of the brachial plexus
      and spinal cord were reviewed retrospectively. Brachial plexus paralysis in such
      dual injuries tends to be diagnosed and treated late and the prognosis is usually
      poor. The associated injuries, which were all on the same side as the plexus
      lesion, were to the head (nine cases), shoulder girdle (five), thorax (nine) and
      upper limb (seven). These other injuries were responsible for the delayed
      diagnosis of brachial plexus paralysis and the poor prognosis was probably
      because of the delay in starting treatment and the severity of the associated
      injuries. When such injuries are detected in patients with spinal cord trauma, it
      is important to consider the possibility of involvement of the brachial plexus.

PMID- 16645112
TI  - Displaced fractures of the neck of the radius in adults. An excellent long-term
      outcome.
AB  - We have reviewed 20 women and three men aged 22 to 73 years, who had sustained a
      Mason type-IIb fracture of the neck of the radius 14 to 25 years earlier. There
      were 19 patients with displacement of the fractures of 2 mm to 4 mm, of whom 13
      had been subjected to early mobilisation and six had been treated in plaster for
      one to four weeks. Of four patients with displacement of 4 mm to 8 mm, three had
      undergone excision and one an open reduction of the head of radius. A total of 21
      patients had no subjective complaints at follow-up, but two had slight impairment
      and occasional elbow pain. The mean range of movement and strength of the elbow
      were not impaired. The elbows had a higher prevalence of degenerative changes
      than the opposite side, but no greater reduction of joint space. Mason type-IIb
      fractures have an excellent long-term outcome if operation is undertaken when the
      displacement of the fracture exceeds 4 mm.

PMID- 16645113
TI  - Salvage of the radial head in chronic adult Monteggia fractures. Report of four
      cases.
AB  - Four men who presented with chronic dislocation of the radial head and nonunion
      or malunion of the ulna were reviewed after open reduction of the radial head and
      internal fixation of the ulna in attempted overcorrection. Their mean age was 37
      years (28 to 46) and the mean interval between injury and reconstruction was nine
      months (4 to 18). The mean follow-up was 24 months (15 to 36). One patient who
      had undergone secondary excision of the radial head was also followed up for
      comparison. The three patients who had followed the treatment protocol had nearly
      normal flexion, extension and supination and only very occasional pain. All had
      considerable loss of pronation which did not affect patient satisfaction.
      Preservation of the radial head in chronic adult Monteggia fractures appears to
      be a promising mode of treatment.

PMID- 16645114
TI  - Non-invasive distal femoral expandable endoprosthesis for limb-salvage surgery in
      paediatric tumours.
AB  - We report our early experience with the use of a non-invasive distal femoral
      expandable endoprosthesis in seven skeletally immature patients with osteosarcoma
      of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the
      time of surgery. The prosthesis was lengthened at appropriate intervals in
      outpatient clinics, without anaesthesia, using the principle of electromagnetic
      induction. The patients were functionally evaluated using the Musculoskeletal
      Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The
      prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean
      knee flexion of 110 degrees (100 degrees to 120 degrees ). The mean
      Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed
      in two patients; one developed a flexion deformity of 25 degrees at the knee
      joint, which was subsequently overcome and one died of disseminated disease. The
      early results from patients treated with this device have been encouraging. The
      implant avoids multiple surgical procedures, general anaesthesia and assists in
      maintaining leg-length equality.

PMID- 16645115
TI  - Constrained total hip arthroplasty in a paediatric patient with cerebral palsy
      and painful dislocation of the hip. A case report.
AB  - We describe a patient with cerebral palsy, of normal intelligence, who could not
      walk but who by the age of 16 had been successfully managed with a staged
      bilateral total hip arthroplasty using a constrained liner.

PMID- 16645116
TI  - Osteofibrous dysplasia of the tibia. Is there a need for a radical surgical
      approach?
AB  - Osteofibrous dysplasia is an unusual developmental condition of childhood, which
      almost exclusively affects the tibia. It is thought to follow a slowly
      progressive course and to stabilise after skeletal maturity. The possible link
      with adamantinoma is controversial and some authors believe that they are part of
      one histological process. We retrospectively reviewed 16 patients who were
      diagnosed as having osteofibrous dysplasia initially or on the final histological
      examination. Their management was diverse, depending on the severity of symptoms
      and the extent of the lesion. Definitive (extraperiosteal) surgery was localised
      "shark-bite" excision for small lesions in five patients. Extensive lesions were
      treated by segmental excision and fibular autograft in six patients, external
      fixation and bone transport in four and proximal tibial replacement in one. One
      patient who had a fibular autograft required further excision and bone transport
      for recurrence. Six initially underwent curettage and all had recurrence. There
      were no recurrences after localised extraperiosteal excision or bone transport.
      There were three confirmed cases of adamantinoma. The relevant literature is
      reviewed. We recommend extraperiosteal excision in all cases of osteofibrous
      dysplasia, with segmental excision and reconstruction in more extensive lesions.

PMID- 16645117
TI  - Occipital condylar fractures. Review of the literature and case report.
AB  - Fractures of the occipital condyle are rare. Their prompt diagnosis is crucial
      since there may be associated cranial nerve palsies and cervical spinal
      instability. The fracture is often not visible on a plain radiograph. We report
      the case of a 21-year-old man who sustained an occipital condylar fracture
      without any associated cranial nerve palsy or further injuries. We have also
      reviewed the literature on this type of injury, in order to assess the incidence,
      the mechanism and the association with head and cervical spinal injuries as well
      as classification systems, options for treatment and outcome.

PMID- 16645118
TI  - Fractures of the acetabulum in osteogenesis imperfecta.
AB  - We describe two patients aged 16 and 25 years with osteogenesis imperfecta who
      sustained displaced fractures of the acetabulum following minor trauma. The
      femoral heads were deformed by impact against the acetabular margin and both
      cases underwent surgical reconstruction. The quality of the bone and soft tissues
      made the operations challenging. There were potential complications specific to
      osteogenesis imperfecta, including bleeding, the creation of secondary fracture
      lines and shredding of the soft-tissue. The cases provide useful guidelines for
      addressing these difficulties.

PMID- 16645119
TI  - Recurrent synovial chondromatosis of the knee after radical synovectomy and
      arthrodesis.
AB  - We describe a case of highly refractory synovial chondromatosis, which recurred
      despite four arthroscopic synovectomies, a chemical synovectomy, two open
      synovectomies and an arthrodesis. A review of the literature revealed one similar
      case. Both presented with marked joint stiffness suggesting a poor prognosis.
      Although arthrodesis may relieve short-term symptoms it does not prevent further
      recurrence of disease.

PMID- 16645120
TI  - Neglected trans-scaphoid trans-styloid volar dislocation of the lunate. Late
      result following open reduction and K-wire fixation.
AB  - A rare case of radiocarpal dislocation is presented. The lunate and proximal pole
      of the scaphoid were displaced in a volar and proximal direction. The injury was
      missed initially and the patient was subsequently operated on six weeks later.
      Open reduction and internal fixation of the scaphoid was performed and this was
      followed by an uneventful postoperative period, with a satisfactory functional
      outcome at the eight-year follow-up, despite carpal instability non-dissociative
      dorsal intercalated segmental instability configuration of the carpus. We believe
      that although open reduction in neglected cases carries the potential risks of
      avascular necrosis and nonunion of the affected carpal bones, an attempt should
      be made to restore the anatomy of the carpus.

PMID- 16645121
TI  - An immunohistological study of the integration at the bone-tendon interface after
      reconstruction of the anterior cruciate ligament in rabbits.
AB  - We studied bone-tendon healing using immunohistochemical methods in a rabbit
      model. Reconstruction of the anterior cruciate ligament was undertaken using
      semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were
      performed at one, two, four and eight weeks after the operation. The expression
      of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the
      bone-tendon interface was very similar to that in the endochondral ossification.
      Some of the type-III collagen in the outer layer of the graft, which was
      deposited at a very early phase after the operation, was believed to have matured
      into Sharpey-like fibres. However, remodelling of the tendon grafted into the
      bone tunnel was significantly delayed when compared with this ossification
      process. To promote healing, we believe that it is necessary to accelerate
      remodelling of the tendon, simultaneously with the augmentation of the
      ossification.

PMID- 16645122
TI  - Cartilage-bone mismatch in the dysplastic trochlea. An MRI study.
AB  - Trochlear dysplasia is an important anatomical abnormality in symptomatic
      patellar instability. Our study assessed the mismatch between the bony and
      cartilaginous morphology in patients with a dysplastic trochlea compared with a
      control group. MRI scans of 25 knees in 23 patients with trochlear dysplasia and
      in 11 patients in a randomly selected control group were reviewed retrospectively
      in order to assess the morphology of the cartilaginous and bony trochlea. Inter-
      and intra-observer error was assessed. In the dysplastic group there were 15
      women and eight men with a mean age of 20.4 years (14 to 30). The mean bony
      sulcus angle was 167.9 degrees (141 degrees to 203 degrees), whereas the mean
      cartilaginous sulcus angle was 186.5 degrees (152 degrees to 214 degrees; p <
      0.001). In 74 of 75 axial images (98.7%) the cartilaginous contour was different
      from the osseous contour on subjective assessment, the cartilage exacerbated the
      abnormality. Our study shows that the morphology of the cartilaginous trochlea
      differs markedly from that of the underlying bony trochlea in patients with
      trochlear dysplasia. MRI is necessary in order to demonstrate the pathology and
      to facilitate surgical planning.

PMID- 16645123
TI  - The role of the dorsal vertebral cortex in the stability of transpedicular
      screws. A biomechanical study in human cadaveric vertebrae.
AB  - The aim of this biomechanical study was to investigate the role of the dorsal
      vertebral cortex in transpedicular screw fixation. Moss transpedicular screws
      were introduced into both pedicles of each vertebra in 25 human cadaver
      vertebrae. The dorsal vertebral cortex and subcortical bone corresponding to the
      entrance site of the screw were removed on one side and preserved on the other.
      Biomechanical testing showed that the mean peak pull-out strength for the
      inserted screws, following removal of the dorsal cortex, was 956.16 N. If the
      dorsal cortex was preserved, the mean peak pullout strength was 1295.64 N. The
      mean increase was 339.48 N (26.13%; p = 0.033). The bone mineral density
      correlated positively with peak pull-out strength. Preservation of the dorsal
      vertebral cortex at the site of insertion of the screw offers a significant
      increase in peak pull-out strength. This may result from engagement by the final
      screw threads in the denser bone of the dorsal cortex and the underlying
      subcortical area. Every effort should be made to preserve the dorsal vertebral
      cortex during insertion of transpedicular screws.

PMID- 16645124
TI  - A novel class of positive allosteric modulators of metabotropic glutamate
      receptor subtype 1 interact with a site distinct from that of negative allosteric
      modulators.
AB  - We recently reported a novel class of compounds, represented by 3-cyano-N-(1,3
      diphenyl-1H-pyrazol-5-yl)benzamide (CD-PPB), that act as positive allosteric
      modulators (potentiators) of metabotropic glutamate receptor (mGluR) subtype 5.
      Studies of CDPPB analogs revealed that some compounds in this series serve also
      as positive allosteric modulators of mGluR1. Although CDPPB is selective for
      mGluR5 relative to other mGluR subtypes, several CDPPB analogs also showed 2.5
      fold potentiation of glutamate-induced calcium transients in cells expressing
      mGluR1 at 10 muM, with 4-nitro-N-(1,4-diphenyl-1H-pyrazol-5-yl)benzamide (VU-71)
      being selective for mGluR1. In previous studies, we found that two structural
      classes of mGluR5-selective allosteric potentiators, including CDPPB, share a
      common binding site with the allosteric mGluR5 antagonist 2-methyl-6
      (phenylethynyl)pyridine. Negative allosteric modulators of mGluR1, regardless of
      structural class, have been reported to bind to a common allosteric antagonist
      site on this receptor. However, neither the novel CDPPB analogs nor previously
      identified allosteric mGluR1 potentiators [e.g., (S)-2-(4-fluorophenyl)-1
      (toluene-4-sulfonyl)pyrrolidine (Ro 67-7476), ethyl diphenylacetylcarbamate (Ro
      01-6128), and butyl (9H-xanthene-9-carbonyl)carbamate (Ro 67-4853)] displaced the
      binding of [(3)H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1
      ethanone (R214127), a high-affinity radioligand for the allosteric antagonist
      site on mGluR1 at concentrations several orders of magnitude higher than those
      required to induce allosteric potentiation of mGluR1 responses. These data
      suggest that allosteric potentiators of mGluR1 act at a site that is distinct
      from that of allosteric antagonists of mGluR1. Site-directed mutagenesis revealed
      that valine at position 757 in transmembrane V of mGluR1a is crucial for the
      activity of multiple classes of allosteric mGluR1 potentiators.

PMID- 16645125
TI  - Oligomerization of recombinant and endogenously expressed human histamine H(4)
      receptors.
AB  - In this study, we report the homo- and hetero-oligomerization of the human
      histamine H(4)R by both biochemical (Western blot and immobilized metal affinity
      chromatography) and biophysical [bioluminescence resonance energy transfer and
      time-resolved fluorescence resonance energy transfer (tr-FRET)] techniques. The
      H(4)R receptor is the most recently discovered member of the histamine family of
      G-protein-coupled receptors. Using specific polyclonal antibodies raised against
      the C-terminal tail of the H(4)R, we demonstrate the presence of H(4)R oligomers
      in human embryonic kidney 293 and COS-7 cells heterologously overexpressing
      H(4)Rs and putative native H(4)R oligomers in human phytohaemagglutinin blasts
      endogenously expressing H(4)Rs. Moreover, we show that H(4)R homo-oligomers are
      formed constitutively, are formed at low receptor densities (300 fmol/mg of
      protein), and are present at the cell surface, as detected by tr-FRET. The
      formation of these oligomers is independent of N-glycosylation and is not
      modulated by H(4)R ligands, covering the full spectrum of agonists, neutral
      antagonists, and inverse agonists. Although we show H(4)R homo-oligomer formation
      at physiological expression levels, the detection of H(1)R-H(4)R hetero-oligomers
      was achieved only at higher H(1)R expression levels and are most likely not
      physiologically relevant.

PMID- 16645126
TI  - Carotid artery stenting before CABG: a better alternative to treat concomitant
      coronary and carotid artery disease.

PMID- 16645127
TI  - Low-dose aspirin for stroke prevention.

PMID- 16645128
TI  - Does the MOSES study provide sufficient evidence for Eprosartan against
      Nitrendipine?

PMID- 16645129
TI  - Shunt-associated migraines respond favorably to changes in work conditions.

PMID- 16645130
TI  - Meta-analysis of antidepressant treatment for patients with poststroke
      depression.

PMID- 16645131
TI  - Blood-brain barrier disruption by low-frequency ultrasound.
AB  - BACKGROUND AND PURPOSE: A recent study showed a dramatic increase in cerebral
      hemorrhage comprising atypical locations with low-frequency ultrasound-mediated
      recombinant tissue plasminogen activator-thrombolysis in humans. Here, we provide
      a possible explanation for this phenomenon by a side effect observed in a study
      using the similar ultrasound device. METHODS: The study was originally undertaken
      to investigate by transcranial Doppler sonography, positron emission tomography
      and perfusion MRI whether transcranial application of wide-field low-frequency
      ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral
      small vessel disease. RESULTS: Showing no clear positive effect on cerebral
      hemodynamics in 4 patients and on cerebral perfusion (positron emission
      tomography) in 2 patients, the study has been terminated early because of a
      remarkable side effect in the first patient (a 62 year-old man) undergoing
      perfusion-MRI: detection of frontoparietal extravasation of Gadolinium contrast
      agent (applied during MRI perfusion imaging preinsonation) on MRI immediately
      postinsonation. CONCLUSIONS: Abnormal permeability of the human blood-brain
      barrier can be induced by wide-field low-frequency insonation. The observed
      excessive bleeding rate with low-frequency sonothrombolysis might thus be
      attributable to primary blood-brain barrier disruption by ultrasound.

PMID- 16645132
TI  - Model of hospital-supported discharge after stroke.
AB  - BACKGROUND AND PURPOSE: Readmission rate within 6 months after a stroke is 40% to
      50%. The purpose of the project was to evaluate whether an interdisciplinary
      stroke team could reduce length of hospital stay, readmission rate, increase
      patient satisfaction and reduce dependency of help. METHODS: One hundred and
      ninety-eight patients with acute stroke were randomized into 103 patients whose
      discharge was supported by an interdisciplinary stroke team and 95 control
      patients who received standard aftercare. Baseline characteristics were
      comparable in the 2 groups. The patients were evaluated after 6 and 12 months
      regarding functional status and need for help. RESULTS: Length of hospital
      admission was insignificantly shorter in the intervention compared with the
      control group (35.2 versus 39.8 days). There was no significant difference in
      readmission, GP-visits, and primary health care services. Furthermore, there was
      no significant difference in functional scores or patient satisfaction.
      CONCLUSIONS: In this setting we could not show benefit of an interdisciplinary
      stroke team supporting patients at discharge perhaps because standard aftercare
      was very efficient already.

PMID- 16645133
TI  - Clinical features and outcome in North American adults with moyamoya phenomenon.
AB  - BACKGROUND AND PURPOSE: To describe baseline clinical features and outcomes of
      adults with moyamoya phenomenon treated at a single North American institution.
      METHODS: We identified 34 adults with moyamoya phenomenon by review of
      angiographic records. Clinical presentation and baseline stroke risk factors were
      obtained by chart review. Follow-up was obtained prospectively. A 5-year Kaplan
      Meier stroke risk was calculated. RESULTS: The median age was 42 (range 20 to 79)
      years. Twenty-five were women. The initial symptom was ischemia, hemorrhage, or
      asymptomatic in 24, 7, and 3 patients, respectively. Twenty-two had bilateral
      involvement and 12 had unilateral moyamoya vessels. Baseline stroke risk factors
      were similar between groups. The median follow-up in 31 living patients was 5.1
      (range 0.2 to 19.6) years. Fourteen patients were treated with surgical
      revascularization (20 total hemispheres). In medically treated symptomatic
      hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the
      initial symptom and 27% after angiographic diagnosis. Patients with bilateral
      involvement presenting with ischemic symptoms were at the highest risk of
      subsequent stroke (n=17, 5-year risk of stroke with medical treatment after first
      symptom of 82%). In surgically treated hemispheres, the 5-year risk of
      perioperative or subsequent ipsilateral stroke or death was 17%. This was
      significantly different compared with medical treatment after first symptom
      (P=0.02) but not after angiographic diagnosis. CONCLUSIONS: Moyamoya phenomenon
      in North American adults is associated with a high risk of recurrent stroke,
      particularly those with bilateral involvement and ischemic symptoms. These data
      suggest a potential benefit with surgery if diagnosis could be made earlier.

PMID- 16645134
TI  - Cilostazol protects against brain white matter damage and cognitive impairment in
      a rat model of chronic cerebral hypoperfusion.
AB  - BACKGROUND AND PURPOSE: White matter lesions contribute to cognitive impairment
      in poststroke patients. The present study was designed to assess the
      neuroprotective mechanisms of cilostazol, a potent inhibitor of type III
      phosphodiesterase, through signaling pathways that lead to activation of
      transcription factor cAMP-responsive element binding protein (CREB)
      phosphorylation using rat chronic cerebral hypoperfusion model. METHODS: Rats
      underwent bilateral common carotid artery ligation. They were divided into the
      cilostazol group (n=80) and the vehicle (control) group (n=80). Performance at
      the Morris water maze task and immunohistochemistry for 4-hydroxy-2-nonenal
      (HNE), glutathione-S-transferase-pi (GST-pi), ionized calcium-binding adaptor
      molecule 1, phosphorylated CREB (p-CREB), Bcl-2, and cyclooxygenase-2 (COX-2)
      were analyzed at baseline and at 3, 7, 14, 21, and 28 days after hypoperfusion.
      RESULT: Cilostazol significantly improved spatial learning memory (6.8+/-2.3
      seconds; P<0.05) at 7 days after hypoperfusion. Cilostazol markedly suppressed
      accumulation of HNE-modified protein and loss of GST-pi-positive oligodendrocytes
      in the cerebral white matter during the early period after hypoperfusion
      (P<0.05). Cilostazol upregulated p-CREB and Bcl-2 (P<0.05), increased COX-2
      expression, and reduced microglial activation in the early period of
      hypoperfusion. CONCLUSIONS: Our results indicate that cilostazol exerts a brain
      protective effect through the CREB phosphorylation pathway leading to
      upregulation of Bcl-2 and COX-2 expressions and suggest that cilostazol is
      potentially useful for the treatment of cognitive impairment in poststroke
      patients.

PMID- 16645135
TI  - Stroke rehabilitation in Europe: what do physiotherapists and occupational
      therapists actually do?
AB  - BACKGROUND AND PURPOSE: Physiotherapy (PT) and occupational therapy (OT) are key
      components of stroke rehabilitation. Little is known about their content. This
      study aimed to define and compare the content of PT and OT for stroke patients
      between 4 European rehabilitation centers. METHODS: In each center, 15 individual
      PT and 15 OT sessions of patients fitting predetermined criteria were videotaped.
      The content was recorded using a list comprising 12 therapeutic categories. A
      generalized estimating equation model was fitted to the relative frequency of
      each category resulting in odds ratios. RESULTS: Comparison of PT and OT between
      centers revealed significant differences for only 2 of the 12 categories:
      ambulatory exercises and selective movements. Comparison of the 2 therapeutic
      disciplines on the pooled data of the 4 centers revealed that ambulatory
      exercises, transfers, exercises, and balance in standing and lying occurred
      significantly more often in PT sessions. Activities of daily living, domestic
      activities, leisure activities, and sensory, perceptual training, and cognition
      occurred significantly more often in OT sessions. CONCLUSIONS: This study
      revealed that the content of each therapeutic discipline was consistent between
      the 4 centers. PT and OT proved to be distinct professions with clear demarcation
      of roles.

PMID- 16645136
TI  - Cortical perfusion measurement by indocyanine-green videoangiography in patients
      undergoing hemicraniectomy for malignant stroke.
AB  - BACKGROUND AND PURPOSE: Assessment of cerebral perfusion during neurosurgical
      procedures would be beneficial to identify areas at risk and to guide placement
      of monitoring probes. Therefore, we have adapted near-infrared indocyanine-green
      (ICG) videoangiography to assess cortical perfusion intraoperatively. METHODS:
      ICG videoangiography was performed intraoperatively in 6 patients after
      decompressive hemicraniectomy for middle cerebral artery stroke. Flow maps of
      cortical perfusion were generated with IC-CALC 1.1 software by calculating the
      ratio of difference in fluorescence intensity and rise time. RESULTS: Excellent
      visualization of cerebral arteries, cortical perfusion and collateral circulation
      via leptomeningeal anastomoses could be demonstrated in all cases. Flow maps
      revealed high spatial resolution and showed heterogeneous maple-leaf-shaped
      hypoperfusion. 26.5+/-13.7% and 29.0+/-9.1% of the exposed cortical surface
      (141+/-18 cm2) demonstrated core and penumbral flow, respectively. CONCLUSIONS:
      ICG videoangiography appears to be a valuable tool to precisely detect relative
      cortical tissue perfusion. Thus, it may provide useful research data on the
      pathophysiology of human stroke, help surgeons to maintain adequate brain
      perfusion intraoperatively, and simplify adequate placement of tissue probes to
      monitor critically hypoperfused brain tissue.

PMID- 16645137
TI  - Statin use and sex-specific stroke outcomes in patients with vascular disease.
AB  - BACKGROUND AND PURPOSE: Although statins reduce the risk of stroke in patients
      with coronary heart disease, possible differing effects of statins on stroke
      outcomes based on sex remain uncertain. We investigated the relationships between
      statin use and sex-specific stroke incidence, severity, and mortality. METHODS:
      Data from 3 trials of oral glycoprotein IIb/IIIa inhibitors (first and second
      Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events
      postacute cOroNary sYndromes [SYMPHONY] and Blockade of the glycoprotein IIb/IIIa
      Receptor to Avoid Vascular Occlusion [BRAVO]) were pooled and stroke outcomes
      compared among 8191 baseline statin users versus 14,752 nonusers. Time-to-event
      data were modeled with proportional hazards regression. Stroke severity was
      assessed retrospectively with the Canadian Neurological Scale (CNS) based on
      records with scoreable neurological examinations. RESULTS: A total of 217
      subjects had strokes (0.95%). Statin users had a lower risk of stroke in
      unadjusted (hazard ratio [HR], 0.69; 95% CI, 0.51 to 0.92) and risk-adjusted
      models (HR, 0.72; 95% CI, 0.53 to 0.97). There was no difference in stroke
      mortality with statin use (P=0.8). CNS scores could be assigned to 106 of the
      subjects, with no difference in severity among statin users and nonusers (median
      CNS=10.5 in users versus CNS=9.75 in nonusers; P=0.14). Women had more severe
      strokes than men (median CNS=10.5 in men versus 9.5 in women; Poisson regression
      P=0.035). Women had more severe strokes after adjustment for statin use (P=0.03)
      and the combination of statin use, atrial fibrillation, and age (P=0.03).
      CONCLUSIONS: In patients included in these clinical trials of oral glycoprotein
      IIb/IIIa inhibitors, statin use is associated with a reduced risk of stroke but
      not severity or mortality. Women had more severe strokes than men, a difference
      that was not explained by baseline characteristics or statin use.

PMID- 16645138
TI  - Persistent infarct hyperintensity on diffusion-weighted imaging late after stroke
      indicates heterogeneous, delayed, infarct evolution.
AB  - BACKGROUND AND PURPOSE: Some infarcts have persistently hyperintense areas on
      diffusion-weighted MRI (DWI) even at 1 month after stroke, whereas others have
      become isointense to normal brain. We hypothesized that late DWI hyperintensity
      reflected different infarct evolution compared with areas that were isointense by
      1 month. METHODS: We recruited patients prospectively with ischemic stroke,
      performed DWI and perfusion-weighted MRI (PWI) on admission, at 5 days, 14 days,
      and 1 month after stroke, and assessed functional outcome at 3 months (Rankin
      Scale). Patient characteristics and DWI/PWI values were compared for patients
      with or without "still hyperintense" infarct areas on 1-month DWI. RESULTS: Among
      42 patients, 27 (64%) had "still hyperintense" infarct regions at 1 month, mostly
      in white matter. Patients with "still hyperintense" regions at 1 month had lower
      baseline apparent diffusion coefficient ratio (ADCr; mean+/-SD 0.76+/-0.12 versus
      0.85+/-0.12; hyperintense versus isointense; P<0.05), prolonged reduction of ADCr
      (repeated-measures ANOVA; P<0.01), no difference in baseline perfusion but
      delayed normalization of mean transit time (P<0.05) and cerebral blood flow
      ratios (repeated measures ANOVA; P<0.05), initially more severe stroke, and worse
      3-month outcome than patients whose lesions were isointense by 1 month.
      CONCLUSIONS: The late DWI lesion hyperintensity emphasizes the heterogeneity in
      temporal evolution of stroke injury and suggests ongoing "ischemia." Lower
      baseline ADCr precedes delayed perfusion normalization, suggesting that worse
      cell swelling impedes reperfusion. Further study is required to determine
      underlying mechanisms and any potential for subacute intervention to improve
      recovery.

PMID- 16645139
TI  - Motor cortex activation during treatment may predict therapeutic gains in paretic
      hand function after stroke.
AB  - BACKGROUND AND PURPOSE: Functional brain imaging after stroke offers insight into
      motor network adaptations. This exploratory study examined whether motor cortical
      activation captured during arm-focused therapy can predict paretic hand
      functional gains. METHODS: Eight hemiparetic patients had serial functional MRI
      (fMRI) while performing a pinch task before, midway, and after 2 weeks of
      constraint-induced therapy. The Wolf Motor Function Test (WMFT) was performed
      before and after intervention. RESULTS: There was a linear reduction in
      ipsilateral (contralesional) primary motor (M1) activation (voxel counts) across
      time. The midpoint M1 Laterality Index anticipated post-therapeutic change in
      time to perform the WMFT. The change in ipsilateral M1 voxel count (pre- to mid-)
      correlated with the change in mean WMFT time (pre- to post-). CONCLUSIONS: The
      relationship between brain activation during treatment and functional gains
      suggests a use for serial fMRI in predicting the success and optimal duration for
      a focused therapeutic intervention.

PMID- 16645140
TI  - Increased expression of cyclooxygenase-2 mediates enhanced contraction to
      endothelin ETA receptor stimulation in endothelial nitric oxide synthase knockout
      mice.
AB  - The aim of this study was to determine whether prolonged loss of NO activity, in
      endothelial NO synthase knockout (eNOS(-/-)) mice, influences endothelin (ET) ETA
      receptor-mediated smooth muscle contraction and, if so, to define the underlying
      mechanism(s). In isolated endothelium-denuded abdominal aortas, contractions to
      the selective ETA receptor agonist ET-1(1-31) were significantly increased in
      aortas from eNOS(-/-) compared with wild-type (WT) mice. In contrast,
      contractions to the alpha1-adrenergic agonist phenylephrine or the thromboxane
      (TX) A2 analog U-46619 were similar between eNOS(-/-) and WT mice.
      Immunofluorescent and Western blot analysis demonstrated that the aortic
      expression of ETA receptors was decreased in eNOS(-/-) compared with WT mice.
      Contractions evoked by ET-1(1-31), but not phenylephrine, were reduced by
      inhibition of cyclooxygenase-2 (COX-2) (indomethacin or celecoxib) or of
      TXA2/prostaglandin H2 receptors (SQ-29548). After COX inhibition, contractions to
      ET-1(1-31) were no longer increased and were actually decreased in eNOS(-/-)
      compared with WT aortas. Western blot analysis revealed that endothelium-denuded
      abdominal aortas express COX-2, but not COX-1, and that expression of COX-2 was
      significantly increased in eNOS(-/-) compared with WT mice. Contractions to the
      COX substrate arachidonic acid were also increased in eNOS(-/-) aortas.
      Furthermore, ET-1(1-31) but not phenylephrine stimulated production of the TXA2
      metabolite TXB2, which was increased in eNOS(-/-) compared with WT aortas.
      Therefore, COX-2 plays a crucial and selective role in ETA-mediated smooth muscle
      contraction. Furthermore, COX-2 expression is increased in eNOS(-/-) mice, which
      overcomes a reduced expression of ETA receptors and enables a selective increase
      in contraction to ETA receptor stimulation.

PMID- 16645141
TI  - Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via
      Akt-endothelial nitric oxide synthase activation and prevent neointimal
      hyperplasia.
AB  - We investigated whether the mobilization of endothelial progenitor cells (EPCs)
      by exogenous erythropoietin (Epo) promotes the repair of injured endothelium.
      Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire
      injury of the femoral artery of mice. Neointimal formation was inhibited by Epo
      to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold
      increase in reendothelialized area of day 14 denuded vessels, 55% of which was
      derived from bone marrow (BM) cells. Epo increased the circulating Sca-1(+)/Flk
      1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO dependently. BM
      replacement by GFP- or beta-galactosidase-overexpressing cells showed that Epo
      stimulated both differentiation of BM-derived EPCs and proliferation of resident
      ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) in the Epo-induced
      neoendothelium, where the expression of Epo receptor was upregulated. Epo induced
      Akt/eNOS phosphorylation and NO synthesis on EPCs and exerted an antiapoptotic
      action on wire-injured arteries. In conclusion, Epo treatment inhibits the
      neointimal hyperplasia after arterial injury in an NO-dependent manner by acting
      on the injured vessels and mobilizing EPCs to the neo-endothelium.

PMID- 16645142
TI  - Extracellular matrix remodeling and organization in developing and diseased
      aortic valves.
AB  - Heart valve disease is an important cause of morbidity and mortality worldwide.
      Little is known about valve disease pathogenesis, but increasing evidence
      implicates a genetic basis for valve disease, suggesting a developmental origin.
      Although the cellular and molecular processes involved in early valvulogenesis
      have been well described, less is known about the regulation of valve
      extracellular matrix (ECM) organization and valvular interstitial cell (VIC)
      distribution that characterize the mature valve structure. Histochemistry,
      immunohistochemistry, and electron microscopy were used to examine ECM
      organization, VIC distribution, and cell proliferation during late valvulogenesis
      in chicken and mouse. In mature valves, ECM organization is conserved across
      species, and developmental studies demonstrate that ECM stratification begins
      during late embryonic cusp remodeling and continues into postnatal life. Cell
      proliferation decreases concomitant with ECM stratification and VIC
      compartmentalization. Explanted, stenotic bicuspid aortic valves (BAVs) from
      pediatric patients were also examined. The diseased valves exhibited disruption
      of the highly organized ECM and VIC distribution seen in normal valves. Cusps
      from diseased valves were thickened with increased and disorganized collagens and
      proteoglycans, decreased and fragmented elastic fibers, and cellular disarray
      without calcification or cell proliferation. Taken together, these studies show
      that normal valve development is characterized by spatiotemporal coordination of
      ECM organization and VIC compartmentalization and that these developmental
      processes are disrupted in pediatric patients with diseased BAVs.

PMID- 16645143
TI  - Arachidonate 5-lipoxygenase variants in atherosclerosis, obesity, and bone
      traits.

PMID- 16645144
TI  - A new role for calmodulin in ion channel biology.

PMID- 16645145
TI  - Silent inward rectifier K+ channels in hypercholesterolemia.

PMID- 16645146
TI  - Partnering up for cardiac hypertrophy.

PMID- 16645147
TI  - Smad3 mediates angiotensin II- and TGF-beta1-induced vascular fibrosis: Smad3
      thickens the plot.

PMID- 16645148
TI  - Synergism of hematopoietic cytokines for infarct repair.

PMID- 16645149
TI  - Compartmentation of cyclic nucleotide signaling in the heart: the role of A
      kinase anchoring proteins.
AB  - The activation of the cyclic nucleotide protein kinase A (PKA) and PKG by their
      respective second messengers is responsible for the modulation of many cellular
      functions in the heart including cardiac hypertrophy, strength of contraction,
      and ion flux. However, several studies have revealed that a general increase in
      cyclic nucleotide concentration in the cell is not sufficient for the specific
      regulation of target proteins. These studies found that PKA and PKG must be
      colocalized with their targets to ensure spatial-temporal control of substrate
      phosphorylation. This compartmentation of cyclic nucleotide signaling is
      accomplished by tethering the protein kinases with their respective substrates
      through the association with scaffolding proteins. For cAMP signaling, A-kinase
      anchoring proteins (AKAPs) provide a molecular mechanism for cAMP
      compartmentation, allowing for the precise control of PKA-mediated
      phosphorylation events. (cAMP, PKA, AKAP, PKG).

PMID- 16645150
TI  - Stem cells as a source of regenerative cardiomyocytes.
AB  - The realization of regenerative cardiac medicine depends on the availability of
      cardiomyocytes in sufficient numbers for transplantation of cardiac tissue and
      the accompanying blood vessels. Embryonic stem (ES) cells, bone marrow (BM) stem
      cells, and tissue-derived stem cells are all potential cell sources. Although ES
      cells are highly proliferative and suitable for mass production, an efficient
      protocol is yet to be established to ensure selective cardiomyocyte induction
      using these cells. Recent advances in developmental biology have clarified the
      involvement of critical factors in cardiomyocyte differentiation, including bone
      morphogenic protein and Wnt signaling proteins, and such factors have the
      potential to improve the efficiency of stem cell induction. Initial studies of
      the intracoronary administration of BM mononuclear cells after myocardial
      infarction has yielded promising results; however, intensive investigation of the
      underlying molecular mechanisms at play as well as double-blinded clinical trials
      will be necessary to establish the extent of both migration of the BM stem cells
      into the damaged cardiac tissue and their differentiation into cardiomyocytes.
      Several types of cardiac tissue stem cells have also been reported, but an
      accurate and extensive comparison of these cells with regard to their
      characteristics and multipotency remains to be done. An integrative study
      involving developmental biology, stem cell biology, and tissue engineering is
      required to achieve the full potential of cardiac regeneration.

PMID- 16645152
TI  - Less effect of intranasal than oral hormone therapy on factors associated with
      venous thrombosis risk in healthy postmenopausal women.
AB  - OBJECTIVE: To compare the effects of intranasal and oral administration of 17beta
      estradiol (E2) and norethisterone(acetate) [NET(A)] in healthy postmenopausal
      women on activated protein C (APC) resistance and other hemostatic parameters
      associated with venous thrombosis. METHODS AND RESULTS: In this 2-center,
      randomized, double-blind, 1-year trial, 90 postmenopausal women (56.6+/-4.7 years
      of age) received daily either an intranasal spray with 175 microg/275 microg
      E2/NET (n=47) or 1 mg/0.5 mg oral E2/NETA (n = 43). Normalized APC sensitivity
      ratios (nAPCsr) were determined with a thrombin generation-based APC resistance
      test. After 1 year, the increase in nAPCsr was smaller in the intranasal than in
      the oral group: 11% (95% CI, 1% to 22%) versus 53% (95% CI, 37% to 72%). Overall,
      the decrease in antithrombin and increase in prothrombin fragment 1+2 (F1+2) were
      smaller and the decrease in free protein S larger in the intranasal compared with
      the oral group after 1 year. In both groups, the decreases in protein C and
      prothrombin, and the increase in d-dimer were similar. CONCLUSIONS: Compared with
      oral E2/NETA therapy, intranasal administration of E2/NET had less effect on APC
      resistance and on a number of other parameters associated with venous thrombosis.
      This observation suggests the possibility of a lower venous thrombosis risk for
      intranasal E2/NET compared with oral therapy.

PMID- 16645151
TI  - Signaling and functions of angiopoietin-1 in vascular protection.
AB  - Angiopoietin-1 (Ang1) has powerful vascular protective effects: suppressing
      plasma leakage, inhibiting vascular inflammation, and preventing endothelial
      death. Preclinical studies indicate that Ang1 may be therapeutically useful in a
      number of situations, including treatment of edema, endotoxemia, and transplant
      arteriosclerosis. However, the ligand has also been implicated in vessel
      remodeling, induction of angiogenesis and pulmonary hypertension, indicating that
      strategies to minimize any deleterious effects while optimizing vessel protection
      are likely to be needed. This review surveys the published data on vascular
      protective effects of Ang1 and highlights the therapeutic potential of this
      ligand, as well as possible limitations to its use. We also consider the data on
      Ang1 receptors and speculate on how to maximize therapeutic benefit by targeting
      the Tie receptors.

PMID- 16645153
TI  - Cardiomyocyte-specific overexpression of NO synthase-3 protects against
      myocardial ischemia-reperfusion injury.
AB  - OBJECTIVE: The protective effect of NO synthase-3 (eNOS)-derived NO in limiting
      myocardial ischemia-reperfusion (MI-R) injury is well established. We reported
      previously that systemic genetic overexpression of eNOS attenuates MI-R injury.
      The purpose of the current study was to investigate tissue-specific genetic
      overexpression of the human eNOS gene. METHODS AND RESULTS: To accomplish this,
      we used 2 distinct murine models of transgenic overexpression, a cardiomyocyte
      specific eNOS overexpresser (CS eNOS-Tg) under the control of the alpha-myosin
      heavy chain promoter, and a systemic eNOS transgenic mouse (SYS eNOS-Tg) under
      control of the native eNOS promoter with an upstream endothelial enhancer
      element. Mice were subjected to 30 or 45 minutes of left coronary artery ischemia
      and 24 or 72 hours of reperfusion. CS eNOS-Tg mice displayed significantly
      decreased infarct size beyond that of mice with systemic overexpression.
      Additionally, CS eNOS-Tg mice exhibited better preservation of cardiac function
      compared with SYS eNOS-Tg mice after myocardial infarction. CONCLUSIONS: These
      results provide evidence that site-specific targeting of eNOS gene therapy may be
      more advantageous in limiting MI-R injury and subsequent cardiac dysfunction.

PMID- 16645154
TI  - Involvement of the antimicrobial peptide LL-37 in human atherosclerosis.
AB  - OBJECTIVE: Antimicrobial peptides are effector molecules of the innate immune
      system. To understand the function of vascular innate immunity in
      atherosclerosis, we investigated the role of LL-37, a cathelicidin antimicrobial
      peptide, in the disease process. METHODS AND RESULTS: Using real-time polymerase
      chain reaction, we found a 6-fold increase in human cationic antimicrobial
      protein 18/LL-37 transcript in human atherosclerotic lesions compared with normal
      arteries. Immunohistochemical analysis of atherosclerotic plaques showed that LL
      37 was expressed mainly by macrophages and some endothelial cells. Western blot
      demonstrated existence of active LL-37 peptide and abundant proprotein in
      atheroma specimens. To understand the functional implication of LL-37 production
      in atherosclerosis, the transcription profile was assessed in endothelial cells
      treated with LL-37. Our data show that LL-37 induces expression of the adhesion
      molecule intercellular adhesion molecule-1 and the chemokine monocyte
      chemoattractant protein 1 in endothelial cells. Intriguingly, Chlamydia
      pneumoniae withstood the antimicrobial activity of LL-37 in vitro, although
      inflammatory response was induced on infection. CONCLUSIONS: LL-37 is produced in
      atherosclerotic lesions, where it may function as an immune modulator by
      activating adhesion molecule and chemokine expression, thus enhancing innate
      immunity in atherosclerosis.

PMID- 16645155
TI  - Nitric oxide and endoplasmic reticulum stress.
AB  - Nitric oxide (NO) is a multifunctional biomolecule involved in a variety of
      physiological and pathological processes, including regulation of blood vessel
      dilatation and anti-arteriosclerotic effects. However, a large amount of NO is
      toxic to the host and causes several diseases such as apoptosis, septic shock,
      and diabetes mellitus. Inducible-form NO synthase is induced in inflammatory
      diseases, including insulitis and arteriosclerosis. Endoplasmic reticulum (ER)
      stress pathway was first identified as a cellular response pathway induced by the
      accumulation of unfolded proteins in ER to preserve ER functions. Later it was
      found that ER stress pathway is also activated by various cellular stresses to
      protect cells, but when stresses are severe, apoptosis is induced to remove
      damaged cells. It is reported that NO and reactive oxygen species disturb ER
      functions, then ER stress-mediated apoptosis pathway is activated. CHOP/GADD153,
      which belongs to C/EBP transcription factor family, is induced in this process
      and mediates apoptosis. ER stress pathway induced by NO can be involved in the
      pathogenesis of various vascular diseases.

PMID- 16645156
TI  - Protection of endothelial survival by peroxisome proliferator-activated receptor
      delta mediated 14-3-3 upregulation.
AB  - OBJECTIVE: To determine the role of prostacyclin (PGI2) in protecting endothelial
      cells (ECs) from apoptosis and elucidate the protective mechanism. METHODS AND
      RESULTS: To evaluate the effect of PGI2 on EC survival, we treated ECs with Ad
      COX1/PGIS (Ad-COPI), which augmented selectively PGI2 production or
      carbaprostacyclin (cPGI2) followed by H2O2 for 4 hours. Ad-COPI inhibited annexin
      V-positive cells and blocked caspase 3 activation. cPGI2 inhibited apoptosis in a
      concentration-dependent manner. L-165041 had a similar effect, suggesting the
      involvement of peroxisome proliferator-activated receptor-delta (PPARdelta). ECs
      expressed functional PPARdelta. PPARdelta overexpression enhanced whereas
      PPARdelta knockdown by small interfering RNA abrogated the antiapoptotic action
      of cPGI2 and L-165041. Our results show for the first time that PGI2 stimulated
      14-3-3alpha expression via PPARdelta activation. cPGI2 and L-165041 induced
      binding oaf PPARdelta to PPAR response elements located between -1426 and -1477
      of 14-3-3alpha promoter region, thereby activating 14-3-3alpha promoter activity
      and protein expression. Upregulation of 14-3-3alpha proteins resulted in an
      increase in Bad binding to 14-3-3alpha and a reduction in Bad translocation to
      mitochondria. CONCLUSIONS: PGI2 protects ECs from H2O2-induced apoptosis by
      inducing PPARdelta binding to 14-3-3alpha promoter, thereby upregulating 14-3
      3alpha protein expression. Elevated 14-3-3alpha augments Bad sequestration and
      prevents Bad-triggered apoptosis.

PMID- 16645157
TI  - Contribution of gene sequence variations of the hepatic cytochrome P450 3A4
      enzyme to variability in individual responsiveness to clopidogrel.
AB  - OBJECTIVE: Metabolic activity of cytochrome P450 (CYP) 3A4 has been associated
      with clopidogrel response variability. Because metabolic activity of CYP3A4 is
      genetically regulated, we hypothesized that genetic variations of this enzyme may
      contribute to clopidogrel response variability. METHODS AND RESULTS: The
      CYP3A4*1B, CYP3A4*3, IVS7+258A>G, IVS7+894C>T, and IVS10+12G>A polymorphisms of
      the CYP3A4 gene were assessed in 82 patients in a steady phase of clopidogrel
      therapy. Glycoprotein (platelet glycoprotein (GP) IIb/IIIa receptor activation
      and platelet aggregation were assessed. A cohort of 45 clopidogrel-naive patients
      was studied to determine the modulating effects of these polymorphisms after
      loading dose (300 mg) administration. Only the IVS7+258A>G, IVS7+894C>T, and
      IVS10+12G>A polymorphisms were sufficiently polymorphic. During the steady phase
      of clopidogrel treatment, IVS10+12A allele carriers had reduced GP IIb/IIIa
      activation (P=0.025) and better responsiveness (P=0.02); similarly, clopidogrel
      naive patients carriers of the IVS10+12A allele had reduced GP IIb/IIIa
      activation during the first 24 hours after a loading dose (P=0.025), increased
      platelet inhibition (P=0.006), and a more optimal drug response (P=0.003). This
      polymorphism did not influence platelet aggregation profiles. No association was
      observed between the other polymorphisms and clopidogrel responsiveness.
      CONCLUSIONS: The IVS10+12G>A polymorphism of the CYP3A4 gene modulates platelet
      activation in patients treated with clopidogrel and may therefore contribute to
      clopidogrel response variability.

PMID- 16645158
TI  - Comparative effects of paclitaxel and rapamycin on smooth muscle migration and
      survival: role of AKT-dependent signaling.
AB  - OBJECTIVE: Advances in stent technology have enabled the delivery of drugs to
      improve outcomes after stent deployment. However, the optimal payloads for stents
      are not clear, and the appropriate stent-based therapies for high-risk patients,
      such as diabetics, have not been clearly established. METHODS AND RESULTS: We
      used smooth muscle cell culture models to compare the activities of rapamycin and
      paclitaxel. Smooth muscle cells were grown in normal or high glucose to induce
      insulin resistance. Both paclitaxel and rapamycin activate mitogen-activated
      protein kinase pathways similarly. However, rapamycin potently activates AKT
      dependent signaling, an effect that overrides the downregulation of this pathway
      by insulin resistance and that causes phosphorylation of the AKT-dependent
      transcription factor FOXO1. This effect is associated with attenuation of the
      anti-migratory effects of rapamycin under high glucose conditions that are not
      observed with paclitaxel, as well as with increased protection against ceramide
      induced cytotoxicity, both of which are dependent on FOXO1 phosphorylation.
      CONCLUSIONS: Differences between the ability of rapamycin and paclitaxel to
      activate AKT may account for their differential cell survival and antichemotactic
      activities. These observations may provide a basis for understanding clinical
      differences between rapamycin- and paclitaxel-coated stents. The approaches used
      in these studies can be expanded to other candidate stent payloads as a method
      for triage in preclinical studies.

PMID- 16645159
TI  - Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow
      cell implantation for functional therapeutic angiogenesis.
AB  - OBJECTIVE: Autologous bone marrow mononuclear cell (BM-MNC) implantation into
      ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration
      is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is
      requisite for vascular maturation during angiogenesis. We examined the impacts of
      combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on
      therapeutic angiogenesis in a rabbit model of hind limb ischemia. METHODS AND
      RESULTS: Rabbits were divided into 4 groups: phosphate-buffered saline (control),
      500 microg Ang-1 plasmid (Ang-1), 1 x 10(6) autologous BM-MNCs (BMC), and Ang-1
      plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic
      score and capillary density compared with the control (P<0.05), but the Ang-1
      gene therapy alone did not improve transcutaneous oxygen pressure (TcO2) and skin
      ulcer score. However, the combination group showed a significant improvement in
      not only angiographic score and capillary density (P<0.05) but also TcO2 (P<0.05)
      and skin ulcer score. These efficacies were greater in the combination group
      compared with the BMC group. CONCLUSIONS: This Ang-1 gene and BM-MNC combination
      therapy enhances not only quantitative but also qualitative angiogenesis in
      ischemic tissues. Moreover, the combination therapy will enable a reduction in
      the amount of BM aspiration required for significant therapeutic angiogenesis.

PMID- 16645160
TI  - Enhanced excitability and suppression of A-type K+ current of pancreas-specific
      afferent neurons in a rat model of chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is a relatively common disorder, characterized by
      glandular insufficiency and chronic, often intractable, pain. The mechanism of
      pain in CP is poorly understood. We have previously developed a model of
      trinitrobenzene sulphonic acid (TNBS)-induced CP that results in nociceptive
      sensitization in rats. This study was designed to examine changes in the
      excitability and alteration of voltage-gated K(+) currents of dorsal root ganglia
      (DRG) neurons innervating the pancreas. CP was induced in adult rats by an
      intraductal injection of TNBS. DRG neurons innervating the pancreas were
      identified by 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate
      fluorescence labeling. Perforated patch-clamp recordings were made from acutely
      dissociated DRG neurons from control and TNBS-treated rats. Pancreas-specific DRG
      neurons displayed more depolarized resting potentials in TNBS-treated rats than
      those in controls (P < 0.02). Some neurons from the TNBS-treated group exhibited
      spontaneous firings. TNBS-induced CP also resulted in a dramatic reduction in
      rheobase (P < 0.05) and a significant increase in the number of action potentials
      evoked at twice rheobase (P < 0.05). Under voltage-clamp conditions, neurons from
      both groups exhibited transient A-type (I(A)) and sustained outward rectifier
      K(+) currents (I(K)). Compared with controls, the average I(A) but not the
      average I(K) density was significantly reduced in the TNBS-treated group (P <
      0.05). The steady-state inactivation curve for I(A) was displaced by
      approximately 20 mV to more hyperpolarized levels after the TNBS treatment. These
      data suggest that TNBS treatment increases the excitability of pancreas-specific
      DRG neurons by suppressing I(A) density, thus identifying for the first time a
      specific molecular mechanism underlying chronic visceral pain and sensitization
      in CP.

PMID- 16645161
TI  - IL-1beta signaling in cat lower esophageal sphincter circular muscle.
AB  - In a cat model of acute experimental esophagitis, resting in vivo lower
      esophageal sphincter (LES) pressure and in vitro tone are lower than in normal
      LES, and the LES circular smooth muscle layer contains elevated levels of IL
      1beta that decrease the LES tone of normal cats. We now examined the mechanisms
      of IL-1beta-induced reduction in LES tone. IL-1beta significantly reduced
      acetylcholine-induced Ca(2+) release in Ca(2+)-free medium, and this effect was
      partially reversed by catalase, demonstrating a role of H(2)O(2) in these
      changes. IL-1beta significantly increased the production of H(2)O(2), and the
      increase was blocked by the p38 MAPK inhibitor SB-203580, by the cytosolic
      phospholipase A(2) (cPLA(2)) inhibitor AACOCF3, and by the NADPH oxidase
      inhibitor apocynin, but not by the MEK1 inhibitor PD-98059. IL-1beta
      significantly increased the phosphorylation of p38 MAPK and cPLA(2). IL-1beta
      induced cPLA(2) phosphorylation was blocked by SB-203580 but not by AACOCF3,
      suggesting sequential activation of p38 MAPK-phosphorylating cPLA(2). The IL
      1beta-induced reduction in LES tone was partially reversed by AACOCF3 and by the
      Ca(2+)-insensitive PLA(2) inhibitor bromoenol lactone (BEL). IL-1beta
      significantly increased cyclooxygenase (COX)-2 and PGE(2) levels. The increase in
      PGE(2) was blocked by SB-203580, AACOCF3, BEL, and the COX-2 inhibitor NS-398 but
      not by PD-98059 or the COX-1 inhibitor valeryl salicylate. The data suggested
      that IL-1beta reduces LES tone by producing H(2)O(2), which may affect Ca(2+)
      release mechanisms and increase the synthesis of COX-2 and PGE(2). Both H(2)O(2)
      and PGE(2) production depend on sequential activation of p38 MAPK and cPLA(2).
      cPLA(2) activates NADPH oxidases, producing H(2)O(2), and may produce arachidonic
      acid, converted to PGE(2) via COX-2.

PMID- 16645162
TI  - Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer
      subjects using solid-state high-resolution manometry.
AB  - This study aimed to use a novel high-resolution manometry (HRM) system to
      establish normative values for deglutitive upper esophageal sphincter (UES)
      relaxation. Seventy-five asymptomatic controls were studied. A solid-state HRM
      assembly with 36 circumferential sensors spaced 1 cm apart was positioned to
      record from the hypopharynx to the stomach. Subjects performed ten 5-ml water
      swallows and one each of 1-, 10-, and 20-ml volume swallows. Pressure profiles
      across the UES were analyzed using customized computational algorithms that
      measured 1) the relaxation interval (RI), 2) the median intrabolus pressure
      (mIBP) during the RI, and 3) the deglutitive sphincter resistance (DSR) defined
      as mIBP/RI. The automated analysis succeeded in confirming bolus volume
      modulation of both the RI and the mIBP with the mean RI ranging from 0.32 to 0.50
      s and mIBP ranging from 5.93 to 13.80 mmHg for 1- and 20-ml swallows,
      respectively. DSR was relatively independent of bolus volume. Peak pharyngeal
      contraction during the return to the resting state postswallow was almost 300
      mmHg, again independent of bolus volume. We performed a detailed analysis of
      deglutitive UES relaxation with a novel HRM system and customized software. The
      enhanced spatial resolution of HRM allows for the accurate, automated assessment
      of UES relaxation and intrabolus pressure characteristics, in both cases
      confirming the volume-dependent effects and absolute values of these parameters
      previously demonstrated by detailed analysis of concurrent manometry/fluoroscopy
      data. Normative values were established to aid in future clinical and
      investigative studies.

PMID- 16645164
TI  - Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required
      for beta-globin transcription.
AB  - The locus control region (LCR) was thought to be necessary and sufficient for
      establishing and maintaining an open beta-globin locus chromatin domain in the
      repressive environment of the developing erythrocyte. However, deletion of the
      LCR from the endogenous locus had no significant effect on chromatin structure
      and did not silence transcription. Thus, the cis-regulatory elements that confer
      the open domain remain unidentified. The conserved DNaseI hypersensitivity sites
      (HSs) HS-62.5 and 3'HS1 that flank the locus, and the region upstream of the LCR
      have been implicated in globin gene regulation. The flanking HSs bind CCCTC
      binding factor (CTCF) and are thought to interact with the LCR to form a
      "chromatin hub" involved in beta-globin gene activation. Hispanic thalassemia, a
      deletion of the LCR and 27 kb upstream, leads to heterochromatinization and
      silencing of the locus. Thus, the region upstream of the LCR deleted in Hispanic
      thalassemia (upstream Hispanic region [UHR]) may be required for expression. To
      determine the importance of the UHR and flanking HSs for beta-globin expression,
      we generated and analyzed mice with targeted deletions of these elements. We
      demonstrate deletion of these regions alone, and in combination, do not affect
      transcription, bringing into question current models for the regulation of the
      beta-globin locus.

PMID- 16645163
TI  - Constitutive activation of Akt contributes to the pathogenesis and survival of
      mantle cell lymphoma.
AB  - To determine whether the PI3K/Akt signaling pathway is involved in the
      pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation
      status of Akt and multiple downstream targets in primary MCL cases and cell
      lines. Akt was phosphorylated in 12 of 12 aggressive blastoid MCL variants and in
      4 of 4 MCL cell lines. In contrast, phosphorylated Akt was present in only 5 of
      16 typical MCL, 3 at comparable levels to the blastoid cases, and 2 at low
      levels. The presence of p-Akt was accompanied by the phosphorylation of
      p27(kip1), FRKHL-1, MDM2, Bad, mTOR, and p70S6K. Inhibition of the PI3K/Akt
      pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt,
      p27(kip1), FRKHL-1, MDM2, Bad, mTOR, GSK-3beta, IkappaB, and led to cell-cycle
      arrest and apoptosis. Six MCL cases (5 with activated Akt and 1 with inactive
      Akt) and 3 of 4 cell lines showed loss of PTEN expression. PIK3CA mutations were
      not detected. We conclude that constitutive activation of the PI3K/Akt pathway
      contributes to the pathogenesis of MCL and preferentially occurs in blastoid
      variants. One possible mechanism of activation is loss of PTEN expression. These
      data suggest that PI3K/Akt inhibitors may be effective in the treatment of Akt
      activated MCL.

PMID- 16645165
TI  - Fondaparinux is a safe alternative in case of heparin intolerance during
      pregnancy.
AB  - Heparin is the drug of choice for the treatment or the prevention of
      thromboembolic disease during pregnancy. However, treatment options are limited
      when heparin cannot be used because of hypersensitivity skin reactions. Despite
      the recent availability of new anticoagulant agents, data relating to their use
      during pregnancy are lacking. This report describes the successful management
      with fondaparinux, during 150 days, of a pregnant patient with protein S
      deficiency and prior deep vein thrombosis (DVT) who developed heparin and
      danaparoid hypersensitivity.

PMID- 16645166
TI  - Reproductive capability in dogs with canine leukocyte adhesion deficiency treated
      with nonmyeloablative conditioning prior to allogeneic hematopoietic stem cell
      transplantation.
AB  - Nonmyeloablative conditioning regimens are increasingly replacing myeolablative
      conditioning prior to allogeneic hematopoietic stem cell transplantation (SCT).
      The recent advent of these conditioning regimens has limited the assessment of
      the long-term effects of this treatment, including analysis of reproductive
      function. To address the question of reproductive function after nonmyeloablative
      transplantation, we analyzed a cohort of young dogs with the genetic disease
      canine leukocyte adhesion deficiency that were treated with a nonmyeloablative
      dose of 200 cGy total body irradiation followed by matched-littermate SCT. Five
      males and 5 females entered puberty; all 5 males and 4 females subsequently sired
      or delivered litters following transplantation. We demonstrate that fertility is
      intact and dogs have uncomplicated parturitions following nonmyeloablative
      conditioning for SCT. These results are encouraging for children and adults of
      childbearing age who receive similar conditioning regimens prior to allogeneic
      transplantation.

PMID- 16645167
TI  - Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant
      FIP1L1-PDGFRalpha T674I mutant.
AB  - The FIP1L1-PDGFRA oncogene is a common cause of chronic eosinophilic leukemia
      (CEL), and encodes an activated tyrosine kinase that is inhibited by imatinib.
      FIP1L1-PDGFRA-positive patients with CEL respond to low-dose imatinib therapy,
      but resistance due to acquired T674I mutation has been observed. We report here
      the identification of sorafenib as a potent inhibitor of the FIP1 like 1-platelet
      derived growth factor receptor alpha (FIP1L1-PDGFRalpha) (T674I) mutant.
      Sorafenib inhibited the proliferation of FIP1L1-PDGFRalpha and FIP1L1
      PDGFRalpha(T674I)-transformed Ba/F3 cells and induced apoptosis of the EOL-1 cell
      line at a low nanomolar concentration. Western blot analysis confirmed that these
      effects were due to a direct effect on FIP1L1-PDGFRalpha and FIP1L1
      PDGFRalpha(T674I). Sorafenib was recently approved for the treatment of renal
      cell carcinoma. Our data suggest that low doses of sorafenib could be efficient
      for the treatment of FIP1L1-PDGFRA-positive CEL and could be used to overcome
      resistance to imatinib associated with the T674I mutation.

PMID- 16645168
TI  - C/EBPalpha directs monocytic commitment of primary myeloid progenitors.
AB  - C/EBPalpha is required for generation of granulocyte-monocyte progenitors, but
      the subsequent role of C/EBPalpha in myeloid lineage commitment remains
      uncertain. We transduced murine marrow cells with C/EBPalpha-estradiol receptor
      (ER) or empty vector and subjected these to lineage depletion just prior to
      culture in estradiol with myeloid cytokines. This protocol limits biases due to
      lineage-specific effects on developmental kinetics, proliferation, and apoptosis.
      Also, lowering the dose of estradiol reduced activated C/EBPalpha-ER to near the
      physiologic range. C/EBPalpha-ER increased Mac1(+)/Gr1(-)/MPO(-)/low monocytes
      1.9-fold while reducing Mac1(+)/Gr1(+)/MPO(hi) granulocytes 2.5-fold at 48 hours,
      even in 0.01 microM estradiol. This pattern was confirmed morphologically and by
      quantitative polymerase chain reaction (PCR) assay of lineage markers. To
      directly assess effects on immature progenitors, transduced cells were cultured
      for 1 day with and then in methylcellulose without estradiol. A 2-fold increase
      in monocytic compared with granulocytic colonies was observed in IL-3/IL-6/SCF or
      GM-CSF, but not G-CSF, even in 0.01 microM estradiol. C/EBPalpha-ER induced PU.1
      mRNA, and PU.1-ER stimulated monocytic development, suggesting that
      transcriptional induction of PU.1 by C/EBPalpha contributes to monopoiesis. A
      C/EBPalpha variant incapable of zippering with c-Jun did not induce monopoiesis,
      and a variant unable to bind NF-kappaB p50 stimulated granulopoiesis, suggesting
      their cooperation with C/EBPalpha during monocytic commitment.

PMID- 16645169
TI  - Loss of memory B cells impairs maintenance of long-term serologic memory during
      HIV-1 infection.
AB  - Circulating memory B cells are severely reduced in the peripheral blood of HIV-1
      infected patients. We investigated whether dysfunctional serologic memory to non
      HIV antigens is related to disease progression by evaluating the frequency of
      memory B cells, plasma IgG, plasma levels of antibodies to measles, and
      Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting
      cells in patients with primary, chronic, and long-term nonprogressive HIV-1
      infection. We also evaluated the in vitro production of IgM and IgG antibodies
      against measles and S pneumoniae antigens following polyclonal activation of
      peripheral blood mononuclear cells (PBMCs) from patients. The percentage of
      memory B cells correlated with CD4+ T-cell counts in patients, thus representing
      a marker of disease progression. While patients with primary and chronic
      infection had severe defects in serologic memory, long-term nonprogressors had
      memory B-cell frequency and levels of antigen-specific antibodies comparable with
      controls. We also evaluated the effect of antiretroviral therapy on these
      serologic memory defects and found that antiretroviral therapy did not restore
      serologic memory in primary or in chronic infection. We suggest that HIV
      infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated
      antigens and this defect is initiated early in infection. This may have important
      consequences for the response of HIV-infected patients to immunizations.

PMID- 16645170
TI  - Definitive-like erythroid cells derived from human embryonic stem cells coexpress
      high levels of embryonic and fetal globins with little or no adult globin.
AB  - Human embryonic stem cells are a promising tool to study events associated with
      the earliest ontogenetic stages of hematopoiesis. We describe the generation of
      erythroid cells from hES (H1) by subsequent processing of cells present at early
      and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic
      marker emergence suggest that CD45+ hematopoiesis peaks at late D14EB
      differentiation stages, although low-level CD45- erythroid differentiation can be
      seen before that stage. By morphologic criteria, hES-derived erythroid cells were
      of definitive type, but these cells both at mRNA and protein levels coexpressed
      high levels of embryonic (epsilon) and fetal (gamma) globins, with little or no
      adult globin (beta). This globin expression pattern was not altered by the
      presence or absence of fetal bovine serum, vascular endothelial growth factor,
      Flt3-L, or coculture with OP-9 during erythroid differentiation and was not
      culture time dependent. The coexpression of both embryonic and fetal globins by
      definitive-type erythroid cells does not faithfully mimic either yolk sac
      embryonic or their fetal liver counterparts. Nevertheless, the high frequency of
      erythroid cells coexpressing embryonic and fetal globin generated from embryonic
      stem cells can serve as an invaluable tool to further explore molecular
      mechanisms.

PMID- 16645171
TI  - IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a
      STAT-dependent mechanism and induces the expansion of these cells in vivo.
AB  - IL-2 plays a critical role in the maintenance of CD4+CD25+ FOXP3(+) regulatory T
      cells (Tregs) in vivo. We examined the effects of IL-2 signaling in human Tregs.
      In vitro, IL-2 selectively up-regulated the expression of FOXP3 in purified
      CD4+CD25+ T cells but not in CD4+CD25- cells. This regulation involved the
      binding of STAT3 and STAT5 proteins to a highly conserved STAT-binding site
      located in the first intron of the FOXP3 gene. We also examined the effects of
      low-dose IL-2 treatment in 12 patients with metastatic cancer and 9 patients with
      chronic myelogenous leukemia after allogeneic hematopoietic stem cell
      transplantation. Overall, IL-2 treatment resulted in a 1.9 median fold increase
      in the frequency of CD4+CD25+ cells in peripheral blood as well as a 9.7 median
      fold increase in FOXP3 expression in CD3+ T cells. CD56+CD3- natural killer (NK)
      cells also expanded during IL-2 therapy but did not express FOXP3. In vitro
      treatment of NK cells with 5-aza-2'-deoxycytidine restored the IL-2 signaling
      pathway leading to FOXP3 expression, suggesting that this gene was constitutively
      repressed by DNA methylation in these cells. Our findings support the clinical
      evaluation of low-dose IL-2 to selectively modulate CD4+CD25+ Tregs and increase
      expression of FOXP3 in vivo.

PMID- 16645172
TI  - Pulmonary function after exposure to the World Trade Center collapse in the New
      York City Fire Department.
AB  - RATIONALE: On September 11, 2001, the World Trade Center collapse created an
      enormous urban disaster site with high levels of airborne pollutants. First
      responders, rescue and recovery workers, and residents have since reported
      respiratory symptoms and developed pulmonary function abnormalities. OBJECTIVES:
      To quantify respiratory health effects of World Trade Center exposure in the New
      York City Fire Department. MEASUREMENTS: Longitudinal study of pulmonary function
      in 12,079 New York City Fire Department rescue workers employed on or before
      09/11/2001. Between 01/01/1997 and 09/11/2002, 31,994 spirometries were obtained
      and the FEV(1) and FVC were analyzed for differences according to estimated World
      Trade Center exposure intensity. Adjusted average FEV(1) during the first year
      after 09/11/2001 was compared with the 5 yr before 09/11/2001. Median time
      between 09/11/2001 and a worker's first spirometry afterwards was 3 mo; 90% were
      assessed within 5 mo. MAIN RESULTS: World Trade Center-exposed workers
      experienced a substantial reduction in adjusted average FEV(1) during the year
      after 09/11/2001 (372 ml; 95% confidence interval, 364-381 ml; p < 0.001) This
      exposure-related FEV(1) decrement equaled 12 yr of aging-related FEV(1) decline.
      Moreover, exposure intensity assessed by initial arrival time at the World Trade
      Center site correlated linearly with FEV(1) reduction in an exposure intensity
      response gradient (p = 0.048). Respiratory symptoms also predicted a further
      FEV(1) decrease (p < 0.001). Similar findings were observed for adjusted average
      FVC. CONCLUSIONS: World Trade Center exposure produced a substantial reduction in
      pulmonary function in New York City Fire Department rescue workers during the
      first year after 09/11/2001.

PMID- 16645173
TI  - Effects of smoking cessation on lung function and airway inflammation in smokers
      with asthma.
AB  - RATIONALE: Active smoking in asthma is associated with worsening of symptoms,
      accelerated decline in lung function, and impaired response to corticosteroids.
      OBJECTIVES: To examine the short-term effects of smoking cessation on lung
      function, airway inflammation, and corticosteroid responsiveness in smokers with
      asthma. METHODS AND MEASUREMENTS: Smokers with asthma were given the option to
      quit or continue smoking. Both groups underwent spirometry and induced sputum at
      baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical
      beclometasone, airway response to oral prednisolone, and sensitivity of
      peripheral blood lymphocytes to corticosteroids were measured before smoking
      cessation and at 6 wk. MAIN RESULTS: Of 32 subjects recruited, 11 opted to
      continue smoking (smoking control group). Of 21 subjects who opted for smoking
      cessation, 10 quit smoking for 6 wk (quit group). In the comparison of quitters
      with smokers at 6 wk, the mean (confidence interval [CI]) difference in FEV(1)
      was 407 ml (21, 793), p = 0.040, and the proportion of sputum neutrophils was
      reduced by 29 (51, 8), p = 0.039. Total cutaneous vasoconstrictor response score
      to topical beclometasone improved after smoking cessation with a mean (CI)
      difference of 3.56 (0.84, 6.28), p = 0.042, between quitters and smokers. There
      was no change in airway corticosteroid responses after smoking cessation.
      CONCLUSIONS: By 6 wk after smoking cessation, subjects who quit smoking had
      achieved considerable improvement in lung function and a fall in sputum
      neutrophil count compared with subjects who continued to smoke. These findings
      highlight the importance of smoking cessation in asthma.

PMID- 16645174
TI  - Vascular endothelial growth factor modulates matrix metalloproteinase-9
      expression in asthma.
AB  - RATIONALE: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase
      9 (MMP-9) are mediators of airway inflammation and remodeling in asthma.
      OBJECTIVES: This study investigates a potential relationship between VEGF and MMP
      9, and the mechanisms by which VEGF signaling regulates MMP-9 expression in
      asthma. METHODS: We evaluated whether levels of VEGF correlated with levels of
      MMP-9 in the sputum of asthma patients, and the effect of VEGF receptor
      inhibitors on MMP-9 expression in murine model of asthma. MEASUREMENTS AND MAIN
      RESULTS: We have found that levels of VEGF and MMP-9 are significantly higher in
      the sputum of patients with asthma than in healthy control subjects, and a
      significant correlation is found between the levels of VEGF and MMP-9. This study
      with the ovalbumin-induced model of asthma revealed the following typical
      pathophysiologic features of asthma in the lungs: increased numbers of
      inflammatory cells of the airways, airway hyperresponsiveness, increased vascular
      permeability, and increased levels of MMP-9 and VEGF. Administration of VEGF
      receptor inhibitors reduced the pathophysiologic signs of asthma and decreased
      the increased expression of MMP-9 after ovalbumin inhalation. CONCLUSIONS: These
      results indicate that there is a close relationship between VEGF and MMP-9
      expression and that inhibition of VEGF receptor down-regulates the expression of
      MMP-9. These findings suggest that VEGF signaling regulates MMP-9 expression and
      plays a critical role in initiation and maintenance of asthma.

PMID- 16645175
TI  - Ischemia and reperfusion increases susceptibility to ventilator-induced lung
      injury in rats.
AB  - OBJECTIVES: Hemorrhagic shock followed by resuscitation (HSR) commonly triggers
      an inflammatory response that leads to acute respiratory distress syndrome.
      HYPOTHESIS: HSR exacerbates mechanical stress-induced lung injury by rendering
      the lung more susceptible to ventilator-induced lung injury. METHODS: Rats were
      subjected to HSR, and were randomized into an HSR + high tidal volume and zero
      positive end-expiratory pressure (PEEP) or a HSR + low tidal volume with 5 cm
      H(2)O PEEP. A sham-operated rat + high tidal volume and zero PEEP served as a
      control. RESULTS: HSR increased susceptibility to ventilator-induced lung injury
      as evidenced by an increase in lung elastance and the wet/dry ratio and a
      reduction in Pa(O(2)) as compared with the other groups. The lung injury observed
      in the HSR + high tidal volume group was associated with a higher level of
      interleukin 6 in the lung and blood, increased epithelial cell apoptosis in the
      kidney and small intestine villi, and a tendency toward high levels of alanine
      aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and
      creatinine in plasma. CONCLUSIONS: HSR priming renders the lung and kidney more
      susceptible to mechanical ventilation-induced organ injury.

PMID- 16645176
TI  - Ion and fluid transport properties of small airways in cystic fibrosis.
AB  - RATIONALE: Small airways constitute a major site of pathology in cystic fibrosis
      (CF) and provide most of the surface area of the conducting airways of the lung.
      Little is known, however, about the impact of CF on ion and fluid transport in
      small (bronchiolar) airways. OBJECTIVES: To describe the ion and fluid transport
      properties of CF bronchiolar epithelium. METHODS: Primary cultures of human
      bronchial and bronchiolar (non-CF and CF) epithelial cells were obtained. The
      bioelectric properties were studied in Ussing chambers and the airway surface
      liquid (ASL) height was measured with confocal microscopy. MAIN RESULTS: Primary
      cultures of DeltaF508 CF bronchiolar epithelial cells displayed higher
      transepithelial resistance than non-CF cultures, whereas baseline short circuit
      current and amiloride-inhibitable short circuit current were similar in both
      preparations. The ASL height was significantly smaller in CF compared with non-CF
      preparations. In the presence of amiloride, addition of forskolin increased short
      circuit current in non-CF but not in CF bronchiolar cultures, and the ATP-induced
      increase in short circuit current was lower in CF than in non-CF cultures. Non-CF
      bronchiolar preparations displayed larger short circuit current and fluid
      secretion in responses to forskolin than non-CF bronchial preparations,
      suggesting that CFTR-dependent Cl(-) transport may play a more important role in
      the regulation of fluid transport in small airways than in large airways.
      CONCLUSION: In CF small airways, defective Cl(-) secretion combined with
      unregulated (persistent) Na(+) absorption results in ASLdepletion.

PMID- 16645177
TI  - Prone position augments recruitment and prevents alveolar overinflation in acute
      lung injury.
AB  - RATIONALE: Mechanical ventilation in the prone position may be an effective means
      of recruiting nonaerated alveolar units and minimizing ventilation-induced lung
      injury. OBJECTIVES: To evaluate and quantify regional lung volume alterations
      when patients with lobar or diffuse acute lung injury (ALI) were turned prone
      after a recruitment maneuver. METHODS: In 21 patients with ALI, a recruitment
      maneuver was applied in the supine position followed by a multislice spiral
      computed tomography (CT) scan; then, patients were turned prone and a second CT
      scan was performed. MAIN RESULTS: Both the recruitment maneuver and prone
      position resulted in improved oxygenation in patients with lobar ALI. Prone
      position also resulted in increased respiratory system compliance and decreased
      Pa(CO(2)) in lobar ALI. In lobar ALI, the proportion of overinflated and
      nonaerated areas declined, whereas the proportion of well-aerated areas increased
      in the prone position. The decrease in overinflated areas was observed mainly in
      the ventral areas. The dorsal regions showed a decrease in nonaerated areas and
      an increase in well-aerated areas. Recruitment maneuver and prone position
      improved oxygenation but had no effect either on Pa(CO(2)) or on the respiratory
      system compliance of patients with diffuse ALI. These patients responded to prone
      position with a decrease in nonaerated areas. CONCLUSIONS: Prone position
      recruited the edematous lung further than recruitment maneuvers and reversed
      overinflation, resulting in a more homogeneous distribution of aeration. The
      effects of the prone position were more pronounced in patients with lobar ALI.

PMID- 16645178
TI  - Persistent effects induced by IL-13 in the lung.
AB  - IL-13 overexpression in the lung induces inflammatory and remodeling responses
      that are prominent features of asthma. Whereas most studies have concentrated on
      the development of IL-13-induced disease, far fewer studies have focused on the
      reversibility of IL-13-induced pathologies. This is particularly important
      because current asthma therapy appears to be poor at reversing lung remodeling.
      In this manuscript, we used an externally regulatable transgenic system that
      targets expression of IL-13 to the lung with the aim of characterizing the
      reversibility process. After 4 wk of doxycycline (dox) exposure, IL-13 expression
      resulted in mixed inflammatory cell infiltration, mucus cell metaplasia, lung
      fibrosis, and airspace enlargement (emphysema). After withdrawal of dox, IL-13
      protein levels were profoundly reduced by 7 d and below baseline by 14 d. During
      this time frame, the level of lung eosinophils returned to near normal, whereas
      macrophages, lymphocytes, and neutrophils remained markedly elevated. IL-13
      induced mucus cell metaplasia significantly decreased (91%) 3 wk after withdrawal
      of dox, showing strong correlation with reduced eosinophil levels. In contrast,
      IL-13-induced lung fibrosis did not significantly decline 4 wk after dox
      withdrawal. Importantly, IL-13-induced emphysema persisted, but modestly declined
      4 wk after dox. Examination of transcript expression profiles identified a subset
      of genes that remained increased weeks after transgene expression was no longer
      detected. Notably, numerous IL-13-induced cytokines and enzymes were reversible
      (IL-6 and cathepsins), whereas others were sustained (CCL6 and chitinases) after
      IL-13 withdrawal, respectively. Thus, several hallmark features of IL-13-induced
      lung pathology persist and are dissociated from eosinophilia after IL-13
      overexpression ceases.

PMID- 16645179
TI  - Gob-5 contributes to goblet cell hyperplasia and modulates pulmonary tissue
      inflammation.
AB  - Gob-5 is a member of the calcium-activated chloride channel family and has been
      associated with allergic response in mouse models of pulmonary inflammation. Gene
      expression of Gob-5 has been shown to be induced in allergic airways and has been
      strongly associated with mucin gene regulation and goblet cell hyperplasia. We
      investigated the physiologic role of Gob-5 in murine models of pulmonary
      inflammation using mice deficient in Gob-5. After sensitization and aerosol
      challenge with ovalbumin (OVA), Gob-5 knockout mice exhibit significantly
      increased bronchoalveolar lavage (BAL) inflammation as compared with wild-type
      controls. The augmented inflammation in BAL consisted predominantly of
      neutrophils. Examination of perivascular inflammation revealed that tissue
      inflammation was decreased in OVA-challenged Gob-5-/- mice. OVA-challenged Gob-5
      knockout mice also had decreased goblet cell hyperplasia as well as decreased
      mucus production. These mice also had decreased airway hypersensitivity after
      cholinergic provocation with methacholine. Gob-5 knockout mice were also
      challenged via intranasal LPS, a TLR-4 agonist. Gob-5-/- mice responded with
      increased neutrophilic BAL inflammation and decreased perivascular tissue
      inflammation as compared with wild-type controls. There was little effect on
      goblet cell hyperplasia and mucus production after LPS challenge. These
      observations reinforce findings that associate Gob-5 with goblet cell hyperplasia
      and mucus production in the allergic immune response, but also implicate Gob-5 in
      the regulation of tissue inflammation in the innate immune response.

PMID- 16645180
TI  - Transcriptional regulation of lung cytidylyltransferase in developing transgenic
      mice.
AB  - Lung development is associated with a surge in surfactant phosphatidylcholine
      (PC) production to prepare the newborn for extrauterine breathing. This process
      is associated with a marked increase in the activity of the rate-regulatory
      surfactant enzyme, CTP:phosphocholine cytidylyltransferase (CCTalpha). To
      investigate the molecular basis for developmental activation of CCTalpha, we
      analyzed expression of endogenous CCTalpha and a reporter gene, beta
      galactosidase, in fetal, newborn, and adult promoter-reporter transgenic mice.
      Transgenics harboring approximately 2 kb of the CCTalpha promoter linked upstream
      of a beta-galactosidase reporter gene displayed relatively high expression in
      distal lung epithelia. Endogenous lung CCTalpha and beta-galactosidase
      activities, protein content, and transcript levels displayed maximal expression
      within the newborn period. CCTalpha and beta-galactosidase activities and enzyme
      levels increased with time in cultured fetal lung explants isolated from
      transgenics. Transfectional analysis using CCTalpha promoter-reporter constructs
      in developing rat type II cells revealed that a region encompassing -169/+71
      contained the DNA elements required for perinatal activation. The studies
      demonstrate that developmental induction of surfactant phospholipid is due, at
      least in part, to transcriptional activation of the CCTalpha gene.

PMID- 16645181
TI  - Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice.
AB  - Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as
      a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune
      response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and
      intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged
      with PA developed a cellular immune response characterized by elevations in Th1
      cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung
      lavage fluid, and peribronchovascular granulomatous inflammation composed of T-
      and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage
      fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice
      challenged with Staphylococcus epidermidis (SE), another gram-positive commensal
      of human skin, and BALB/c mice challenged with PA, showed only a modest induction
      of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in
      the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed
      C57BL/6 mice within 24 h after exposure, suggesting that induction of innate
      immunity by PA contributes to the robust, polarized Th1 immune response elicited
      by this bacterium. These findings suggest that PA-induced pulmonary inflammation
      may be a useful model for testing the contributions of both bacterial and host
      factors in the development, maintenance, and resolution of granulomatous
      inflammation in the lung.

PMID- 16645183
TI  - Adapting efficacious interventions: advancing translational research in HIV
      prevention.
AB  - The Human Immunodeficiency Virus (HIV) has infected approximately 1.5 million
      people in the United States. Type 1 translation research (basic research, methods
      development, and efficacy trials) has yielded multiple efficacious behavioral HIV
      prevention programs. Type 2 translation research (dissemination and effectiveness
      studies) has been less prevalent or successful. Adaptation of efficacious
      interventions for culturally diverse populations has received increasing
      researcher attention, and empirical validation of adaptation procedures promises
      to help bridge the gap between Type 1 and Type 2 studies. In this article, the
      authors briefly discuss the development, testing, and dissemination of
      efficacious HIV prevention programs and then focus on research-based principles
      and processes that can guide researchers'adaptation efforts and steps that
      researchers can take to help empower practitioners to conduct science-based
      adaptation. Greater collaboration between researchers and service providers to
      test adaptation frameworks promises to benefit both research and practice.

PMID- 16645184
TI  - Challenges to implementing and sustaining comprehensive mental health service
      programs.
AB  - The President's New Freedom Commission recently concluded that the nation's
      mental health service delivery system is ill equipped to meet the complex needs
      of persons with mental illness. A major contributor to this service quality
      crisis has been the longstanding divergence of research efforts and clinical
      programs. In this article, the authors begin by describing the unique needs of
      persons with serious and persisting psychiatric disorders and the evolution of
      the mental health service system that has attempted to meet these needs. They
      then discuss recent efforts to upgrade services by emphasizing the use of
      evidence-based practices (EBPs) and the research underlying their development.
      Next, they describe the difficulties of using traditional research methods to
      develop and test interventions for persons receiving services at public mental
      health agencies. Finally, they outline the challenges confronted when trying to
      disseminate these EBPs to the wider clinical community.

PMID- 16645185
TI  - Translational research in childhood obesity prevention.
AB  - This article explores the state of translational research in childhood obesity
      prevention. Five phases of translational research and emerging findings from
      basic science that could be useful in the design of obesity prevention programs
      are described. Few intervention studies have been published, and these are
      dominated by Phase 3 trials (efficacy), conducted in school settings, with a
      limited number of studies finding significant effects on Body Mass Index or
      adiposity. Cost-benefit analyses are lacking. Research is needed to translate
      basic science findings into novel interventions (Phases 1 and 2) and to translate
      programs with known behavior change capability into dissemination trials (Phase
      5). Translation can be facilitated by enhanced communication between basic
      science and prevention science researchers, the development of interventions for
      underused settings, using novel strategies, support by institutions and funding
      agencies for translation, and the design of interventions with translation in
      mind.

PMID- 16645186
TI  - Translation in tobacco and drug abuse prevention research.
AB  - The purpose of this article is to describe the translation of research on tobacco
      and drug abuse prevention from basic science to program development to large
      scale program dissemination, and from animal to human studies. Where relevant,
      continuity of translation is discussed by referring to two variables that have
      been studied for their potential relationship to drug use risk in both animals
      and humans: sensation and novelty seeking and low impulse control. Review of the
      research indicates relatively slow translation until the early 1990s. The authors
      recommend several mechanisms to promote more rapid translation across types of
      research that encourage reciprocal rather than unidirectional transmission of
      knowledge to expedite the development and diffusion of more timely, targeted drug
      abuse prevention programs.

PMID- 16645187
TI  - Transforming growth factor-beta1-induced endothelial barrier dysfunction involves
      Smad2-dependent p38 activation and subsequent RhoA activation.
AB  - Lung edema due to increased vascular permeability is a hallmark of acute lung
      injury and acute respiratory distress syndrome. Both p38 and RhoA signaling
      events are involved in transforming growth factor (TGF)-beta1-increased
      endothelial permeability; however, the mechanism by which these pathways
      cooperate is not clear. In this study, we hypothesized that TGF-beta1-induced
      changes in endothelial monolayer permeability and in p38 and RhoA activation are
      dependent on Smad2 signaling. We assessed the role of Smad2 in p38 activation and
      the role of p38 in RhoA activation by TGF-beta1. We found that TGF-beta1 caused
      Smad2 phosphorylation between 0.5 and 1 h of exposure in endothelial cells.
      Knockdown of Smad2 protein prevented TGF-beta1-induced p38 activation and
      endothelial barrier dysfunction. Furthermore, TGF-beta1-enhanced RhoA activation
      was dependent on p38 activation. Inhibition of the RhoA-Rho kinase signaling
      pathway blunted TGF-beta1-induced adherens junction disruption and focal adhesion
      complex formation. In addition, depletion of heat shock protein 27, a downstream
      signaling molecule of p38, did not prevent TGF-beta1-induced endothelial barrier
      dysfunction. Finally, inhibition of de novo protein expression blunted TGF-beta1
      induced RhoA activation and endothelial barrier dysfunction. Our data indicate
      that TGF-beta1 induces endothelial barrier dysfunction involving Smad2-dependent
      p38 activation, resulting in RhoA activation by possible transcriptional
      regulation.

PMID- 16645188
TI  - Stochastic behavior of atrial and ventricular intrinsic cardiac neurons.
AB  - To quantify the concurrent transduction capabilities of spatially distributed
      intrinsic cardiac neurons, the activities generated by atrial vs. ventricular
      intrinsic cardiac neurons were recorded simultaneously in 12 anesthetized dogs at
      baseline and during alterations in the cardiac milieu. Few (3%) identified atrial
      and ventricular neurons (2 of 72 characterized neurons) responded solely to
      regional mechanical deformation, doing so in a tightly coupled fashion (cross
      correlation coefficient r = 0.63). The remaining (97%) atrial and ventricular
      neurons transduced multimodal stimuli to display stochastic behavior.
      Specifically, ventricular chemosensory inputs modified these populations such
      that they generated no short-term coherence among their activities (cross
      correlation coefficient r = 0.21 +/- 0.07). Regional ventricular ischemia
      activated most atrial and ventricular neurons in a noncoupled fashion. Nicotinic
      activation of atrial neurons enhanced ventricular neuronal activity. Acute
      decentralization of the intrinsic cardiac nervous system obtunded its neuron
      responsiveness to cardiac sensory stimuli. Most atrial and ventricular intrinsic
      cardiac neurons generate concurrent stochastic activity that is predicated
      primarily upon their cardiac chemotransduction. As a consequence, they display
      relative independent short-term (beat-to-beat) control over regional cardiac
      indexes. Over longer time scales, their functional interdependence is manifest as
      the result of interganglionic interconnections and descending inputs.

PMID- 16645189
TI  - Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no
      effect on mucus secretion in the ferret trachea.
AB  - Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters
      involved in the regulation of bronchial and pulmonary vascular tone. Published
      studies of the effects of VIP on airway mucus secretion have yielded conflicting
      results. The purpose of this study was to determine the effect of VIP on mucus
      secretion in the ferret trachea and if this effect was influenced by NO. We used
      a sandwich enzyme-linked lectin assay to measure mucin secretion and a
      turbidimetric assay to measure lysozyme (serous cell) secretion from ferret
      tracheal segments. VIP (10(-7) M) increased mucin secretion over 2 h. VIP (10(-9)
      to 10(-5) M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced
      mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric
      VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor
      antagonist) at a 10-fold excess concentration. At all concentrations tested,
      neither NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, nor S
      nitroso-N-acetyl-penicillamine, an NO donor, had any significant effect on
      constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated
      mucin and lysozyme secretion was both time dependent and dose dependent and that
      NO neither stimulates nor inhibits mucus secretion in the ferret trachea.

PMID- 16645190
TI  - Capsaicin-induced activation of pulmonary vagal C fibers produces reflex
      laryngeal closure in the rat.
AB  - Our recent studies show that intravenous administration of capsaicin induces
      enhancement of the intralaryngeal thyroarytenoid (TA) branch but a reduction of
      the intralaryngeal abducent branch, suggesting that the glottis is likely closed
      by capsaicin. The aim of the present study was to examine whether the glottis is
      adducted by intravenous administration of capsaicin. Electromyographic (EMG)
      activity of the TA muscle, subglottal pressure (SGP), and glottal behavior were
      evaluated before and after intravenous administration of capsaicin in male Wistar
      rats that were anesthetized and tracheostomized. Catheters were placed in the
      femoral artery and vein, as well as in the right jugular vein. Low and high doses
      of capsaicin (0.625 and 1.25 microg/kg) produced apnea and increases in the
      amplitude of the TA EMG. This enhancement of the TA EMG was observed during apnea
      as well as during recovery from apnea. Moreover, the onset of the TA EMG was
      advanced such that it commenced earlier during inspiration. Concomitantly, the
      SGP substantially increased. Increases in both the TA EMG and SGP were abolished
      after bilateral sectioning of the recurrent laryngeal nerve. In some animals,
      movement of the vocal folds was recorded by taking a motion picture with a
      digital camera under a surgical microscope. With intravenous administration of
      capsaicin, a tight glottal closure, decreases in blood pressure, and bradycardia
      were observed. These results strongly suggest that glottal closure is reflexively
      induced by intravenous administration of capsaicin and that closure of the
      glottis is beneficial for the defense of the airway and lungs when an animal is
      exposed to environmental irritants.

PMID- 16645191
TI  - Point: cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16645193
TI  - Transduction mechanisms in airway sensory nerves.
AB  - The induction of action potentials in airway sensory nerves relies on events
      leading to the opening of cation channels in the nerve terminal membrane and
      subsequent membrane depolarization. If the membrane depolarization is of
      sufficient rate and amplitude, action potential initiation will occur. The action
      potentials are then conducted to the central nervous system, leading to the
      initiation of various sensations and cardiorespiratory reflexes. Triggering
      events in airway sensory nerves include mechanical perturbation, inflammatory
      mediators, pH, temperature, and osmolarity acting through a variety of ionotropic
      and metabotropic receptors. Action potential initiation can be modulated
      (positively or negatively) through independent mechanisms caused mainly by
      autacoids and other metabotropic receptor ligands. Finally, gene expression of
      sensory nerves can be altered in adult mammals. This neuroplasticity can change
      the function of sensory nerves and likely involve both neurotrophin and use
      dependent mechanisms. Here we provide a brief overview of some of the
      transduction mechanisms underlying these events.

PMID- 16645192
TI  - Central pathways of pulmonary and lower airway vagal afferents.
AB  - Lung sensory receptors with afferent fibers coursing in the vagus nerves are
      broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting
      stretch receptors and bronchopulmonary C fibers. Central terminations of each
      group are found in largely nonoverlapping regions of the caudal half of the
      nucleus of the solitary tract (NTS). Second order neurons in the pathways from
      these receptors innervate neurons located in respiratory-related regions of the
      medulla, pons, and spinal cord. The relative ease of selective activation of
      SARs, and to a lesser extent RARs, has allowed for more complete physiological
      and morphological characterization of the second and higher order neurons in
      these pathways than for C fibers. A subset of NTS neurons receiving afferent
      input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and
      inhibits neurons receiving afferent input from RARs. P-cells and second order
      neurons in the RAR pathway also provide inputs to regions of the ventrolateral
      medulla involved in control of respiratory motor pattern, i.e., regions
      containing a predominance of bulbospinal premotor neurons, as well as regions
      containing respiratory rhythm-generating neurons. Axon collaterals from both P
      cells and RAR interneurons, and likely from NTS interneurons in the C-fiber
      pathway, project to the parabrachial pontine region where they may contribute to
      plasticity in respiratory control and integration of respiratory control with
      other systems, including those that provide for voluntary control of breathing,
      sleep-wake behavior, and emotions.

PMID- 16645195
TI  - Medullary lateral tegmental field neurons influence the timing and pattern of
      phrenic nerve activity in cats.
AB  - In an effort to characterize the role of the medullary lateral tegmental field
      (LTF) in regulating respiration, we tested the effects of selective blockade of
      excitatory (EAA) and inhibitory amino acid (IAA) receptors in this region on
      phrenic nerve activity (PNA) of vagus-intact and vagotomized cats anesthetized
      with dial-urethane. We found distinct patterns of changes in central respiratory
      rate, duration of inspiratory and expiratory phases of PNA (Ti and Te,
      respectively), and I-burst amplitude after selective blockade of EAA and IAA
      receptors in the LTF. First, blockade of N-methyl-D-aspartate (NMDA) receptors
      significantly (P < 0.05) decreased central respiratory rate primarily by
      increasing Ti but did not alter I-burst amplitude. Second, blockade of non-NMDA
      receptors significantly reduced I-burst amplitude without affecting central
      respiratory rate. Third, blockade of GABAA receptors significantly decreased
      central respiratory rate by increasing Te and significantly reduced I-burst
      amplitude. Fourth, blockade of glycine receptors significantly decreased central
      respiratory rate by causing proportional increases in Ti and Te and significantly
      reduced I-burst amplitude. These changes in PNA were markedly different from
      those produced by blockade of EAA or IAA receptors in the pre-Botzinger complex.
      We propose that a proper balance of excitatory and inhibitory inputs to several
      functionally distinct pools of LTF neurons is essential for maintaining the
      normal pattern of PNA in anesthetized cats.

PMID- 16645194
TI  - Advancing age alters the expression of the ryanodine receptor 3 isoform in adult
      rat superior cervical ganglia.
AB  - Sympathetic nerves arising from the superior cervical ganglion (SCG) protect the
      cerebrovasculature during periods of acute hypertension and may play a role in
      homeostasis of target organs. The functions of these nerves depend on calcium
      release triggered by activation of ryanodine receptor (RyR) channels. The
      function of RyR channels is in part dependent on genetic expression and
      regulation by numerous protein modulators such as neuronal nitric oxide synthase
      (nNOS) neurons also found in the SCG. We have shown that release of calcium in
      SCG cells is altered during late maturation and advancing age. However, the
      underlying molecular mechanisms that may in part account for these data are
      elusive. Therefore we used molecular techniques to test the hypothesis that
      advancing age alters the pattern of genetic expression and/or protein levels of
      RyRs and their modulation by nNOS in the SCG in F344 rats aged 6, 12, and 24 mo.
      Surprisingly, ryr1 expression was undetectable in all age groups and ryr2 and
      ryr3 are the predominantly transcribed isoforms in the adult rat SCG. mRNA and
      protein levels for RyR2 isoform did not change with advancing age. However, ryr3
      mRNA levels increased from 6 to 12 mo and declined from 12 to 24 mo. Similarly,
      RyR3 receptor protein levels also increased from 6 to 12 mo and declined from 12
      to 24 mo. Because nNOS and the phosphorylation of the RyRs have been shown to
      modulate the function of RyRs, total phosphorylation and nNOS protein levels were
      analyzed in all age groups. Phosphorylation levels of the RyRs were similar in
      all age groups. However, nNOS protein levels increased from 6 to 12 mo followed
      by decline from 12 to 24 mo. These data suggest that advancing age selectively
      impacts the genetic expression and protein levels of RyR3 as well as modulatory
      nNOS protein levels. In addition, these data may part provide some insight into
      the possible changes in the function of RyRs that may occur with the normal aging
      process.

PMID- 16645196
TI  - Plethysmographic estimation of thoracic gas volume in apneic mice.
AB  - Electrical stimulation of intercostal muscles was employed to measure thoracic
      gas volume (TGV) during airway occlusion in the absence of respiratory effort at
      different levels of lung inflation. In 15 tracheostomized and mechanically
      ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing
      effort available in the early phase of the experiments (TGVsp) was compared with
      those resulting from muscle stimulation (TGVst) at transrespiratory pressures of
      0, 10, and 20 cmH2O. A very strong correlation (r2= 0.97) was found, although
      with a systematically (approximately 16%) higher estimation of TGVst relative to
      TGVsp, attributable to the different durations of the stimulated (approximately
      50 ms) and spontaneous (approximately 200 ms) contractions. Measurements of TGVst
      before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in
      six mice resulted in good agreement between the change in TGVst and the injected
      volume (r2= 0.98). In four mice, TGVsp and TGVst were compared at end expiration
      with air or a helium-oxygen mixture to confirm the validity of isothermal
      compression in the alveolar gas. The TGVst values measured at zero
      transrespiratory pressure in all CBA/Ca mice [0.29 +/- 0.05 (SD) ml] and in
      C57BL/6 (N = 6; 0.34 +/- 0.08 ml) and BALB/c (N = 6; 0.28 +/- 0.06 ml) mice were
      in agreement with functional residual capacity values from previous studies in
      which different techniques were used. This method is particularly useful when TGV
      is to be determined in the absence of breathing activity, when it must be known
      at any level of lung inflation or under non-steady-state conditions, such as
      during pharmaceutical interventions.

PMID- 16645197
TI  - Krabbe disease: psychosine-mediated activation of phospholipase A2 in
      oligodendrocyte cell death.
AB  - Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological
      disorder caused by the pathogenomic accumulation of psychosine
      (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside
      beta-galactosidase. This study underscores the mechanism of action of psychosine
      in the regulation of oligodendrocyte cell death via the generation of
      lysophosphatidylcholine (LPC) and arachidonic acid (AA) by the activation of
      secretory phospholipase A2 (sPLA2). There was a significant increase in the level
      of LPC, indicating a phospholipase A2 (PLA2)-dependent pathobiology, in the
      brains of Krabbe disease patients and those of twitcher mice, an animal model of
      Krabbe disease. In vitro studies of the treatment of primary oligodendrocytes and
      the oligodendrocyte MO3.13 cell line with psychosine also showed the generation
      of LPC and the release of AA in a dose- and time-dependent manner, indicating
      psychosine-induced activation of PLA2. Studies with various pharmacological
      inhibitors of cytosolic phospholipase A2 and sPLA2 and psychosine-mediated
      induction of sPLA2 enzymatic activity in media supernatant suggest that
      psychosine-induced release of AA and generation of LPC is mainly contributed by
      sPLA2. An inhibitor of sPLA2, 7,7-dimethyl eicosadienoic acid, completely
      attenuated the psychosine-mediated accumulation of LPC levels, release of AA, and
      generation of reactive oxygen species, and blocked oligodendroyte cell death, as
      evident from cell survival, DNA fragmentation, and caspase 3 activity assays.
      This study documents for the first time that psychosine-induced cell death is
      mediated via the sPLA2 signaling pathway and that inhibitors of sPLA2 may hold a
      therapeutic potential for protection against oligodendrocyte cell death and
      resulting demyelination in Krabbe disease.

PMID- 16645198
TI  - Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell
      Function.
AB  - The recent Keystone Symposium on Lipid Rafts and Cell Function (March 23-28, 2006
      in Steamboat Springs, CO) brought together biophysicists, biochemists, and cell
      biologists to discuss the structure and function of lipid rafts. What emerged
      from the meeting was a consensus definition of a membrane raft: "Membrane rafts
      are small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid
      enriched domains that compartmentalize cellular processes. Small rafts can
      sometimes be stabilized to form larger platforms through protein-protein and
      protein-lipid interactions." This definition helps to clarify current thinking in
      a field that has been plagued by the heterogeneous and sometimes ephemeral nature
      of its subject.

PMID- 16645199
TI  - FISH analysis for the detection of lymphoma-associated chromosomal abnormalities
      in routine paraffin-embedded tissue.
AB  - Over the last decade, fluorescence in situ hybridization (FISH) has become a
      firmly established technique in the diagnosis and assessment of lymphoid
      malignancies. However, this technique is not wide-ly used in the routine
      diagnostic evaluation of paraffin-embedded biopsies, most likely because of a
      perception that it is technically more demanding. There are also uncertainties
      regarding diagnostic thresholds and the way in which results should be
      interpreted. In this Review, we describe practical strategies for using FISH
      analysis to detect lymphoma-associated chromosomal abnormalities in routine
      paraffin-embedded lymphoma biopsies. Furthermore, we provide proposals on how
      FISH results should be interpreted (including how to calculate cutoff levels for
      FISH probes), recorded, and reported. An online appendix (available at
      http://jmd.amjpathol.org) details various simple, yet robust procedures for
      paraffin FISH analysis; it also provides additional information on the production
      of FISH probes, evaluating and reporting FISH results, sources for reagents and
      equipment, and troubleshooting. We hope that these suggestions will make FISH
      technology for the study of lymphoma biopsies more accessible to routine
      diagnostic and research laboratories.

PMID- 16645200
TI  - Quantitative DNA methylation analysis: the promise of high-throughput epigenomic
      diagnostic testing in human neoplastic disease.

PMID- 16645201
TI  - RCL2, a new fixative, preserves morphology and nucleic acid integrity in paraffin
      embedded breast carcinoma and microdissected breast tumor cells.
AB  - Methacarn and RCL2, a new noncrosslinking fixative, were compared to formalin
      fixed or frozen tissue samples of the same invasive breast carcinoma and were
      evaluated for their effects on tissue morphology and immunohistochemistry as well
      as DNA and RNA integrity. The histomorphology of methacarn- or RCL2-fixed
      paraffin-embedded tumors was similar to that observed with the matched formalin
      fixed tissues. Immunohistochemistry using various antibodies showed comparable
      results with either fixative, leading to accurate breast tumor diagnosis and
      determination of estrogen and progesterone receptors, and HER2 status. Methacarn
      and RCL2 fixation preserved DNA integrity as demonstrated by successful
      amplification and sequencing of large DNA amplicons. Similarly, high-quality RNA
      could be extracted from methacarn- or RCL2-fixed paraffin-embedded MCF-7 cells,
      whole breast tumor tissues, or microdissected breast tumor cells, as assessed by
      electropherogram profiles and real-time reverse transcriptase-polymerase chain
      reaction quantification of various genes. Moreover, tissue morphology and RNA
      integrity were preserved after 8 months of storage. Altogether, these results
      indicate that methacarn, as previously shown, and RCL2, a promising new fixative,
      have great potential for performing both morphological and molecular analyses on
      the same fixed tissue sample, even after laser-capture microdissection, and can
      open new doors for investigating small target lesions such as premalignant breast
      lesions.

PMID- 16645202
TI  - Detection of the single hotspot mutation in the JH2 pseudokinase domain of Janus
      kinase 2 in bone marrow trephine biopsies derived from chronic myeloproliferative
      disorders.
AB  - The recent discovery of a single point mutation in the JH2 pseudokinase domain of
      Janus kinase 2 (JAK2) in a considerable fraction of patients has shed light on
      the molecular pathomechanism in Philadelphia chromosome-negative chronic
      myeloproliferative disorders (Ph- CMPDs). We established a robust and reliable
      method for detection of the JAK2 mutation in bone marrow cells derived from
      archival bone marrow trephines based on polymerase chain reaction and subsequent
      restriction site analysis. In a series of proven Ph- CMPDs classified according
      to World Health Organization criteria (n = 79), we detected the JAK2 mutation in
      90% of polycythemia vera, 22% of cellular prefibrotic chronic idiopathic
      myelofibrosis, 60% of advanced chronic idiopathic myelofibrosis, and 27% of
      essential thrombocythemia. JAK2 mutation was not detected in Ph+ chronic myeloid
      leukemia (n = 5), acute myeloid leukemia (n = 10), acute lymphoblastic leukemia
      (n = 10), secondary erythrocytosis (n = 10), or normal bone marrow (n = 10).
      Restriction site analysis was also suitable for unfixed cell populations derived
      from peripheral blood and bone marrow aspirates. Besides providing support in the
      differential diagnosis of reactive versus neoplastic myeloproliferations, this
      newly developed assay reveals considerable overlaps between histologically
      different disease entities, indicating that additional genetic alterations might
      be responsible for the established differences of CMPD subentities.

PMID- 16645203
TI  - Microsatellite stable colorectal cancers in clinically suspected hereditary
      nonpolyposis colorectal cancer patients without vertical transmission of disease
      are unlikely to be caused by biallelic germline mutations in MYH.
AB  - Microsatellite analysis and immunohistochemistry are commonly used initial
      screening tests for hereditary nonpolyposis colorectal cancer. However, tumors in
      roughly one-half of the patients fulfilling the Bethesda guidelines are
      microsatellite stable. In addition, normal mismatch repair protein expression in
      these tumors suggests that a defect in the mismatch repair system is unlikely.
      Because biallelic MYH mutations occur in patients with both high and low numbers
      of adenomas, we hypothesized that MYH is involved in the tumorigenesis of
      microsatellite stable colorectal cancers in patients without vertical
      transmission of disease and who fulfill the Bethesda guidelines. MYH was analyzed
      in 50 cancer patients and 116 healthy controls by complete genomic DNA
      sequencing. No biallelic germline mutations were identified. One patient was a
      heterozygous carrier for the p.G382D missense mutation, and another patient was a
      heterozygous carrier for the novel missense mutation p.Q484H. We identified six
      common variants, three in the coding region (p.V22M, p.Q324H, and p.S501F) and
      three in adjacent intronic regions (c.157+30A>G, c.462+35G>A, and c.1435-40G>C).
      In summary, biallelic germline mutations of MYH are unlikely to cause colorectal
      cancer in patients sharing clinical features with hereditary nonpolyposis
      colorectal cancer families without mismatch repair defect and therefore cannot
      fill the molecular diagnostic gap in this subgroup of Bethesda-positive patients.

PMID- 16645204
TI  - In vitro transcription amplification and labeling methods contribute to the
      variability of gene expression profiling with DNA microarrays.
AB  - The effect of different amplification and labeling methods on DNA microarray
      expression results has not been previously delineated. To analyze the variation
      associated with widely accepted T7-based RNA amplificationand labeling methods,
      aliquots of the Stratagene Human Universal Reference RNA were labeled using three
      eukaryotic target preparation methods followed by uniform replicate array
      hybridization (Affymetrix U95Av2). Method-dependent variability was observed in
      the yield and size distribution of labeled products, as well as in the gene
      expression results. A significant increase in short transcripts, when compared to
      unamplified mRNA, was observed in methods with long in vitro transcription
      reactions. Intramethod reproducibility showed correlation coefficients >0.99,
      whereas intermethod comparisons showed coefficients ranging from 0.94 to 0.98 and
      a nearly twofold increase in coefficient of variation. Fold amplification for
      each method positively correlated with the number of genes present. Our
      experiments uncovered two factors that introduced significant bias in gene
      expression data: the number of labeled nucleotides, which introduces sequence
      dependent bias, and the length of the in vitro transcription reaction, which
      introduces transcript size-dependent bias. This study provides evidence that
      variability in expression data may be caused, in part, by differences in
      amplification and labeling protocols.

PMID- 16645205
TI  - Analysis of molecular alterations in left- and right-sided colorectal carcinomas
      reveals distinct pathways of carcinogenesis: proposal for new molecular profile
      of colorectal carcinomas.
AB  - To clarify distinct genetic profiles of colorectal cancers based on tumor
      location (left- and right-sided), we evaluated the status of loss of
      heterozygosity (LOH), CpG islands methylation phenotype (CIMP), microsatellite
      instability (MSI), and mutations of p53, Ki-ras, and APC genes in 119 colorectal
      cancers. Statuses of LOH (at 5q, 8p, 17p, 18q, and 22q), MSI, and CIMP (MINT1,
      MINT2, MINT31, MLH-1, MGMT, p14, p16, and RASSF1A) were determined using
      microsatellite polymerase chain reaction and methylation-specific polymerase
      chain reaction coupled with a crypt isolation method, respectively. In addition,
      mutations of p53, Ki-ras, and APC genes were also examined. LOH, MSI, and CIMP
      status allowed us to classify samples into two groups: low or negative and high
      or positive. Whereas the frequency of p53 mutations in the LOH-high status was
      significantly higher in left-sided cancers than in right-sided cancers, CIMP-high
      in the LOH-high status and MSI-positive status were more frequently found in
      right-sided cancers compared with left-sided cancers. Finally, location-specific
      methylated loci were seen in colorectal cancers: type I (dominant in right-sided
      cancer) and type II (common in both segments of cancer). Our data confirm that
      distinct molecular pathways to colorectal cancer dominate in the left and right
      sides of the bowel.

PMID- 16645206
TI  - Examination of gene fusion status in archival samples of alveolar
      rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a
      report from the Children's Oncology Group.
AB  - Alveolar rhabdomyosarcoma (ARMS) is a soft tissue cancer in which chromosomal
      translocations generate PAX3-FKHR and PAX7-FKHR gene fusions. To improve the
      approach for fusion detection in archival samples, we developed a real-time
      reverse transcriptase-polymerase chain reaction assay for these fusion
      transcripts. By incorporating consensus primers and gene-specific probes, both
      presence and subtype of the fusion were determined in one assay. We applied this
      approach to a convenience sample of 78 formalin-fixed, paraffin-embedded ARMS
      tumors from the Intergroup Rhabdomyosarcoma Study (IRS)-III clinical trial and
      obtained satisfactory results in 59 (76%) cases. The distribution of fusion types
      was 35 (59%) PAX3-FKHR, 11 (19%) PAX7-FKHR, and 13 fusion-negative (22%). In a
      subsequent clinical analysis, we found that IRS-III ARMS cases analyzed for
      fusion status had a significantly improved outcome compared to IRS-III ARMS cases
      that were not available for fusion analysis. The basis of this outcome could not
      be explained by known prognostic clinical factors, and multivariate analysis
      confirmed that our convenience sample was not representative of the whole IRS-III
      cohort. In conclusion, although these robust assays provide new opportunities for
      correlative studies of archival material, our first application illustrates an
      important limitation of using a convenience sample for molecular-clinical
      correlative studies.

PMID- 16645208
TI  - Establishment and study of different real-time polymerase chain reaction assays
      for the quantification of cells with deletions of chromosome 7.
AB  - The evaluation of residual disease, which has prognostic value in the treatment
      of hematological malignancies, is currently assessed by scoring a limited number
      of cells by karyotyping and molecular cytogenetics. Real-time polymerase chain
      reaction (PCR) is an easier and more sensitive technique, enables analysis of a
      larger number of cells, and decreases sampling error. However, real-time PCR has
      been applied only to target transcripts of fusion genes. Here, we considered two
      real-time PCR strategies to quantify a number of cells carrying a partial
      deletion of chromosome 7 mixed with normal disomic cells. The first strategy was
      based on the amplification of two sequences, one on chromosome 7 and the other on
      chromosome 14. In the second strategy residual disease was assessed by the ratio
      between the two alleles of a bi-allelic marker, mapped on chromosome 7, measured
      with allele-specific assays. Precision and accuracy of the two approaches were
      tested by reference samples with nominal values of residual disease ranging from
      2 to 95%. As expected the second strategy resulted in more precise and accurate
      monitoring within the range from 5 to 95%. Furthermore, this method may be
      applied to assess the number of dysplastic or neoplastic clones carrying any
      unbalanced chromosome changes.

PMID- 16645207
TI  - Precision and performance characteristics of bisulfite conversion and real-time
      PCR (MethyLight) for quantitative DNA methylation analysis.
AB  - Assays to measure DNA methylation, which are important in epigenetic research and
      clinical diagnostics, typically rely on conversion of unmethylated cytosine to
      uracil by sodium bisulfite. However, no study has comprehensively evaluated the
      precision and performance characteristics of sodium bisulfite conversion and
      subsequent quantitative methylation assay. We developed quantitative real-time
      polymerase chain reaction (MethyLight) to measure percentage of methylated
      reference (PMR, ie, degree of methylation) for the MGMT, MLH1, and CDKN2A (p16)
      promoters. To measure the precision of bisulfite conversion, we bisulfite-treated
      seven different aliquots of DNA from each of four paraffin-embedded colon cancer
      samples. To assess run-to-run variation, we repeated MethyLight five times.
      Bisulfite-to-bisulfite coefficient of variation (CV) of PMR ranged from 0.10 to
      0.38 (mean, 0.21), and run-to-run CV of PMR ranged from 0.046 to 0.60 (mean,
      0.31). Interclass correlation coefficients were 0.74 to 0.84 for the three loci,
      indicating good reproducibility. DNA mixing study with methylated and
      unmethylated DNA showed good linearity of the assay. Of 272 colorectal cancers
      evaluated, most showed PMR either <1 or >10, and promoter methylation (PMR >4)
      was tightly associated with loss of respective protein expression (P < 10(-16)).
      In conclusion, sodium bisulfite conversion and quantitative MethyLight assays
      have good precision and linearity and can be effectively used for high-throughput
      DNA methylation analysis on paraffin-embedded tissue.

PMID- 16645209
TI  - Rapid and sensitive real-time polymerase chain reaction method for detection and
      quantification of 3243A>G mitochondrial point mutation.
AB  - Maternally inherited diabetes and deafness and mitochondrial encephalomyopathy,
      lactic acidosis with stroke-like episodes result from the 3243A>G mitochondrial
      point mutation. Current methods to detect the presence of the mutation have
      limited sensitivity and may lead to potential misclassification of patients with
      low levels of heteroplasmy. Here, we describe development and validation of a
      rapid real-time polymerase chain reaction (PCR) method for detection and
      quantification of levels of heteroplasmy in a single assay. Standard curve
      analysis indicated that the sensitivity of detection was less than 0.1%. Time
      from sample loading to data analysis was 110 minutes. We tested 293 samples
      including 23 known positives, 40 known negatives, and 230 samples from patients
      clinically classified as having type 2 diabetes. All positive samples were
      correctly detected, and of those samples previously quantified, heteroplasmy
      levels determined using the real-time assay correlated well (r(2) = 0.88 and
      0.93) with results from fluorescently labeled PCR-restriction fragment length
      polymorphism and pyrosequencing methods. Screening of 230 patients classified as
      having type 2 diabetes revealed one patient with 0.6% heteroplasmy who had
      previously tested negative by PCR-restriction fragment length polymorphism. Real
      time PCR provides rapid simultaneous detection and quantification of the 3243A>G
      mutation to a detection limit of less than 0.1%, without post-PCR manipulation.

PMID- 16645210
TI  - Molecular monitoring of chronic myelogenous leukemia: identification of the most
      suitable internal control gene for real-time quantification of BCR-ABL
      transcripts.
AB  - Monitoring breakpoint cluster region-Abelson kinase (BCR-ABL) levels in patients
      treated for chronic myelogenous leukemia (CML) has become an integral part of
      patient management. Real-time reverse transcriptase-polymerase chain reaction is
      the method of choice for this purpose because of its high analytical sensitivity
      and reproducibility. Given the variation of RNA quality and quantity in clinical
      specimens, accurate quantitative assessment of BCR-ABL depends on normalization
      of the BCR-ABL signal to an appropriate internal reference. However, the controls
      used by different laboratories vary, and there is no clear consensus on an ideal
      reference due to limited investigations. In this study, we compared nine commonly
      used control genes for three criteria: mRNA abundance, levels in CML and non-CML
      cells, and their degradation kinetics in comparison with BCR-ABL. We found that
      beta-glucuronidase (GUSB) is the most suitable among the nine genes tested.
      Although ABL is most widely used, our data suggest that the amount of ABL is
      different in CML and non-CML cells. Moreover, ABL levels are regulated by
      cellular stress. These findings have a direct impact on current clinical
      laboratory practice and patient care because the use of a proper control gene
      affects the reported levels of BCR-ABL transcripts used for patient management
      decisions.

PMID- 16645211
TI  - Diagnosis of human congenital cytomegalovirus infection by amplification of viral
      DNA from dried blood spots on perinatal cards.
AB  - Congenital human cytomegalovirus (HCMV) infection affects 1% of children and is
      the most common infectious cause of sensorineural hearing loss. Due to the
      difficulty of diagnosing deafness and other neurological disorders in infants,
      affected individuals may not be recognized until much later when active infection
      has resolved and culture is no longer informative. To overcome this problem,
      congenital HCMV infection was diagnosed retrospectively by testing residual blood
      samples collected from newborns and dried on perinatal cards as part of the North
      Carolina Newborn Screening Program. We modified the Qiagen method for purifying
      DNA from dried blood spots to increase the sample size and recovery of the
      lysate. A multiplex, real-time TaqMan polymerase chain reaction assay on an ABI
      7900 instrument measured a highly conserved segment of the HCMV polymerase gene
      and the APOB human control gene. HCMV DNA was detected in blood dried on
      perinatal cards from all seven infants with culture-proven congenital infection,
      and all 24 negative control cases lacked detectable HCMV DNA. Our findings
      suggest that it is possible to diagnose congenital HCMV infection using dried
      blood collected up to 20 months earlier. Further studies are warranted on
      patients with hearing loss or other neurological deficits to determine the
      percentage that is attributable to congenital HCMV infection.

PMID- 16645212
TI  - Validation of a novel ultra-short immunolabeling method for high-quality mRNA
      preservation in laser microdissection and real-time reverse transcriptase
      polymerase chain reaction.
AB  - Laser microdissection allows isolation of tiny samples from tissue sections for
      analysis of gene expression by real-time quantitative polymerase chain reaction
      (PCR). Although immunohistochemical labeling is often required to identify target
      structures, it drastically degrades mRNA so that shortened protocols are needed.
      Here, we present a novel method that allows fluorescence double labeling to be
      performed in only one incubation of 5 minutes. Fab fragments directly coupled to
      fluorochromes are linked to primary antibodies before these complexes are applied
      to sections. We quantified the influences of fixatives, labeling solutions, and
      incubation time on the mRNA yield and compared our method with previously
      proposed protocols. While tissue components, ie, vimentin and Ki67 antigen, were
      sufficiently stained after only 5 minutes of incubation, the new method produced
      a minute loss of mRNA that did not significantly differ from that of untreated
      sections. In contrast, incubation times of 15 and 30 minutes reduced the mRNA
      yield by 99.8 to 99.9%. Furthermore, incubation periods longer than 5 minutes
      critically affected the ratio between the target and housekeeping genes tested by
      factors of up to 10.6. In conclusion, the novel method described here reduces
      mRNA loss and potential ratio shifts to a level that does not significantly
      differ from that of unlabeled samples.

PMID- 16645213
TI  - Denaturing high-performance liquid chromatography: a valid approach for
      identifying NPM1 mutations in acute myeloid leukemia.
AB  - NPM1 gene mutations are the most frequent genetic lesion in the 60% of adult
      acute myeloid leukemias (AMLs) with normal karyotype and no evidence of typical
      fusion genes (BCR/ABL1, PML/RARA, AML1/ETO, CBFB/MYH11, DEK/CAN). Using direct
      sequencing we previously identified six different heterozygous mutants within
      exon 12 encoding the nucleophosmin C-terminus. Because of these mutations the
      shuttling protein nucleophosmin is aberrantly delocalized in the cytoplasm of
      leukemic cells (NPMc+). Here, we designed and tested a denaturing high
      performance liquid chromatography (DHPLC) assay to detect NPM1 mutated variants.
      To assess specificity, sensitivity, reliability, and reproducibility, we analyzed
      DNA from 120 primary adult AMLs and compared DHPLC results with
      immunohistochemistry and sequencing. All electropherogram profiles in the 26
      NPMc+ leukemias were different from the wild type, indicating 100% sensitivity.
      Sequencing categorized mutations A, B, and D, and all mutation A cases gave
      identical elution profiles. The other mutations showed typical chromatograms,
      with mutations B and D differing for one nucleotide. Elution profiles and
      sequencing also identified four new variants. Our results suggest that DHPLC
      detects NPM1mutations as well as direct sequencing and immunohistochemistry,
      providing a helpful approach in the diagnosis of NPMc+ AML.

PMID- 16645214
TI  - The development of a fluorescence in situ hybridization assay for the detection
      of dysplasia and adenocarcinoma in Barrett's esophagus.
AB  - The goal of this study was to identify a set of fluorescence in situ
      hybridization probes for the detection of dysplasia and adenocarcinoma in
      patients with Barrett's esophagus. We examined 170 brushing specimens from 138
      patients with Barrett's esophagus or a history of Barrett's esophagus using
      fluorescence in situ hybridization with probes to 5p15, 5q21-22, centromere 7,
      7p12, 8q24.12-13, centromere 9, 9p21, centromere 17, 17p13.1, 17q11.2-12,
      20q13.2, and centromere Y. Receiver-operator curves were used to determine the
      sensitivity and specificity of various four-probe combinations for detecting low
      grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Endoscopic
      biopsy results were used as the gold standard. Numerous four-probe combinations
      provided a similarly high sensitivity and specificity. Of these, a set consisting
      of probes to 8q24, 9p21, 17q11.2, and 20q13.2 was found to have a sensitivity and
      specificity, respectively, of 70% and 89% for low-grade dysplasia, 84% and 93%
      for high-grade dysplasia, and 94% and 93% for esophageal adenocarcinoma. This
      probe set was chosen for future prospective clinical evaluations based on its
      high sensitivity and specificity, its ability to distinguish adenocarcinoma and
      high-grade or low-grade dysplasia from lesser diagnostic categories, and the
      favorable signal quality for each of the probes.

PMID- 16645215
TI  - Glioma test array for use with formalin-fixed, paraffin-embedded tissue: array
      comparative genomic hybridization correlates with loss of heterozygosity and
      fluorescence in situ hybridization.
AB  - Array-based comparative genomic hybridization (aCGH) is a powerful, high
      throughput tool for whole genome analysis. Until recently, aCGH could only be
      reproducibly performed on frozen tissue samples and with significant tissue
      amounts. For brain tumors however, paraffin-embedded tissue blocks from small
      stereotactic biopsies may be the only tissue routinely available. The development
      of methods to analyze formalin-fixed, paraffin-embedded (FFPE) material therefore
      has the potential to impact molecular diagnosis in a significant way. To this
      end, we constructed a BAC array representing chromosomes 1, 7, 19, and X because
      1p/19q deletion and EGFR gene amplification provide clinically relevant
      information for glioma diagnosis. We also optimized a two-step labeling procedure
      using an amine-modified nucleotide for generating aCGH probes. Using this
      approach, we analyzed a series of 28 FFPE oligodendroglial tumors for alterations
      of chromosomes 1, 7, and 19. We also independently assayed these tumors for
      1p/19q deletion by fluorescence in situ hybridization and by loss of
      heterozygosity analyses. The concordance between aCGH, standard loss of
      heterozygosity and fluorescence in situ hybridization was nearly 100% for the
      chromosomes analyzed. These results suggest that aCGH could offer an improved
      molecular diagnostic approach for gliomas because of its ability to detect
      clinically relevant molecular alterations in small FFPE specimens.

PMID- 16645216
TI  - Detection of common disease-causing mutations in mitochondrial DNA (mitochondrial
      encephalomyopathy, lactic acidosis with stroke-like episodes MTTL1 3243 A>G and
      myoclonic epilepsy associated with ragged-red fibers MTTK 8344A>G) by real-time
      polymerase chain reaction.
AB  - The 3243A>G mutation in the MTTL1 (tRNA(Leu)) gene and the 8344A>G mutation in
      the MTTK (tRNA(Lys)) gene are the most common mutations found in mitochondrial
      encephalomyopathy, lactic acidosis with stroke-like episodes and myoclonic
      epilepsy associated with ragged-red fibers, respectively. These mitochondrial DNA
      mutations are usually detected by conventional polymerase chain reaction followed
      by restriction enzyme digestion and gel electrophoresis. We developed a
      LightCycler real-time polymerase chain reaction assay to detect these two
      mutations based on fluorescence resonance energy transfer technology and melting
      curve analysis. Primers and fluorescence-labeled hybridization probes were
      designed so that the sensor probe spans the mutation site. The observed melting
      temperatures differed in the mutant and wild-type DNA by 9 degrees C for the
      MTTL1 gene and 6 degrees C for the MTTK gene. This method correctly identified
      all 10 samples that were 3243A>G mutation-positive, all 4 samples that were
      8344A>G mutation-positive, and all 30 samples that were negative for both
      mutations, as previously identified by traditional gel-based methods. This
      LightCycler assay is a rapid and reliable technique for molecular diagnosis of
      these mitochondrial gene mutations.

PMID- 16645217
TI  - Rapid one-step carrier detection assay of mucolipidosis IV mutations in the
      Ashkenazi Jewish population.
AB  - Two mutations in the MCOLN1 mucolipidosis IV (ML IV) gene represent approximately
      95% of the mutations in Ashkenazi-Jewish patients with ML IV. The mutations, a
      splice site mutation (IVS3-2A>G) and an approximately 6.4-kb deletion
      (511del6434), account for 72% and 23% of ML IV alleles in this population,
      respectively. An automated high-throughput assay was developed using the 5'
      nuclease (TaqMan) method for the simultaneous detection of both mutations in a
      single reaction. Three fluorescent probes specifically detected wild-type, IVS3
      2A>G, and 511del6434 alleles in each reaction real-time. Data collected were
      automatically analyzed, and genotype results were uploaded into a laboratory
      information management system. The assay was validated using genomic controls,
      demonstrating high robustness and accuracy. Carrier screening of 10,527 samples
      revealed 77 heterozygote carriers of IVS3-2A>G, 25 heterozygote carriers of
      511del6434, and two compound heterozygote of both mutant alleles. The frequency
      of mutated alleles was 0.73% for IVS3-2A>G and 0.24% for 511del6434. The combined
      carrier frequency was 1:103 with predicted disease incidence of 1:42,436
      individuals in this population, slightly lower than previously described
      frequencies. This automated high-throughput assay is labor saving, because two
      mutations can be detected in a single reaction. The method has potential for use
      in other assays requiring simultaneous detection of two mutations.

PMID- 16645218
TI  - Cytogenetic changes associated with myelodysplastic syndrome affecting bone
      marrow engraftment analysis.
AB  - In vitro amplification of polymorphic genetic markers, especially short tandem
      repeats (STRs), has become standard laboratory practice in the monitoring of
      allogeneic bone marrow transplant patients. After initial analysis of donor and
      recipient samples at multiple loci before transplantation, one or more loci are
      used to follow engraftment status in subsequent specimens. We describe an unusual
      pattern of STRs in a transplanted patient with a prior history of refractory
      acute myelogenous leukemia. DNA chimerism studies showed a lack of engraftment at
      1 and 2 months after transplantation. Atypical minor peaks occurred at each of
      three STR loci in the pre-transplant and 2-month post-transplant recipient
      samples. However, these peaks were of equal amplitude as the major corresponding
      allele in the 1-month post-transplant sample. A history of myelodysplasia with
      specific chromosomal deletions before the patient's acute myelogenous leukemia
      diagnosis appears to explain the spurious peaks. STR analysis of blood and
      archival paraffin-embedded tissues collected from the patient at various time
      points before transplantation reflected the evolution, progression, and response
      to therapy of the myelodysplasia. The case illustrates the need for comprehensive
      evaluation of pertinent clinical and laboratory data during engraftment
      monitoring to identify potential sources for error in interpretation of STR
      analysis.

PMID- 16645220
TI  - Allergens.
AB  - What makes an antigen an allergen? This question has been at the core of much
      research regarding the basic mechanisms of allergy as well as the development of
      diagnostic and therapeutic allergen products. Great strides have been made since
      Kjell Aas asked this question in his classic review in Allergy (1), but we appear
      no closer to the answer. The mechanisms leading to allergic reactions have been
      well described in recent years and our understanding of it at the molecular level
      has greatly improved. Conversely, the molecular structures responsible for these
      allergic reactions are not as well understood. Techniques for the isolation,
      identification, and epitope mapping of allergens have greatly enhanced our
      ability to test old and new ideas about what makes an antigen an allergen. We
      continue to search for "major allergens," and when we identify them, we hope to
      delineate "allergenic determinants" and "immunodominant epitopes." Even now,
      unique structural motifs or determinants responsible for allergenicity have not
      yet been identified, and we will probably never find them.

PMID- 16645221
TI  - Structural characterization of pollen allergens.
AB  - The molecular characterization of allergens has accelerated significantly since
      the widespread implementation of modern analytical methods. The combination of
      gene cloning and heterologous protein expression has generated an extensive array
      of allergens that is available for comparative analysis, as well as clinical
      applications. Several internet-accessible allergen databases integrate the
      accumulated information from biomedical research and clinical practice.
      Innovations in classical biophysical methods, such as mass spectrometry, X-ray
      crystallography, and nuclear magnetic resonance spectroscopy, have rendered
      complex biological macromolecules amenable to detailed structural analysis. The
      modern scientific era has realized the synthesis of bioinformatics, molecular
      biology, biochemistry, biophysics, and immunology, and given us the means needed
      to decipher the remaining mysteries of allergies. This article addresses how the
      synergism of modern scientific techniques has hastened our understanding of
      allergies, how these techniques are applied in the identification and
      characterization of allergens, and how these methods assist the rational
      development of clinical tools for allergy diagnosis and treatment.

PMID- 16645222
TI  - T-cell epitopes of food allergens.
AB  - During recent years, a great deal of research has focused on the identification
      of food allergens, their characterization at the molecular level, and the
      investigation of immunological mechanisms responsible for food hypersensitivity.
      Allergen-reactive T-helper 2 cells play a central role in the pathophysiology of
      allergic diseases. After activation with allergens, this subset of CD4(+) T
      lymphocytes produces a spectrum of cytokines that induce high serum levels of
      immunoglobulin E and eosinophilia, which, in turn, mediate the clinical symptoms.
      Furthermore, T-helper 2 cells are present in target organs during the late
      response to allergen exposure. The analysis of the allergic T-cell response,
      including cytokine production and the identification of T-cell epitopes, provides
      important information on the characteristics of food allergens. Therefore, in
      vitro cultures of allergen-specific T-cells derived from peripheral blood or
      different target organs have been of indispensable help. Results obtained from
      such studies may not only contribute to the understanding of cellular mechanisms
      underlying different types of food allergy but also to the development of novel
      strategies for immunotherapy of food allergy.

PMID- 16645223
TI  - Hymenoptera venom allergens.
AB  - Hymenoptera venoms each contain a variety of protein allergens. The major
      components have all been characterized, and most of the amino acid sequences are
      known. This article concentrates on the use of contemporary techniques including
      cloning, mass spectrometry and genomics in the characterization of venom
      allergens, and newer separation techniques for protein isolation. Examples of the
      use of these techniques with venom proteins are presented.

PMID- 16645224
TI  - Innate immune responses to environmental allergens.
AB  - Aero-allergens, including plant pollens, house dust mite particles, fungal
      spores, and mycelium fragments, are continuously inhaled and deposited on the
      airway mucosa. These particles and their soluble components actively interact
      with innate recognition systems present in the mucosal layer (e.g., surfactant
      proteins) and with various receptors present on a diversity of cells in the
      airways. Deposited particles are first removed by active transportation, the rate
      of which is either enhanced or inhibited by components present in the inhaled
      substances. Cleaning further depends on innate recognition, beginning with (a)
      soluble factors released into the mucosal surface layer that bind different bio
      organic components; (b) innate receptors on phagocytic cells, alveolar
      macrophages, and dendritic monocytes; and (c) innate receptors on airway
      epithelial cells. Different innate receptor families (Toll-like receptors [TLRs],
      nucleotide-binding oligomerization domain receptors, and protein-activated
      receptors [PARs]) have been demonstrated on airway cells, including alveolar
      macrophages, monocytes, dendritic cells, and airway tissue cells (e.g.,
      epithelial cells and mast cells). However, although the functional role of these
      receptors has been studied for infectious diseases, the functional role for
      reaction of airways to inhaled bio-organic substances, including allergens, is
      largely unexplored. Indirect evidence for functional interactions has come from
      in vivo animal studies, as well as in vitro studies with monocytes, macrophages,
      and epithelial cells, which have demonstrated release of cytokines and chemokines
      after contact with allergens such as house dust mite, cat, pollen, and fungi.
      Most allergens show direct activation of airway epithelial cells, suggesting a
      role for the innate receptors. However, the role of TLRs, PARs, and other
      receptors was studied for only a limited number of allergens. Current studies
      indicate synergistic interactions between members of the same receptor family
      (TLRs) as well as synergistic interactions between members of different families
      (TLRs, PARs, and nucleotide-binding oligomerization domain receptors), modulating
      responses into feed-forward or inhibitory actions. Study of these synergistic
      interactions and their genetic variations will provide insight regarding how the
      innate immune system determines the inflammatory reactions of the airways and the
      outcome of the T-helper-1- and T-helper-2-type responses to inhaled allergens.

PMID- 16645225
TI  - Advances in the treatment of locally advanced non-nasopharyngeal squamous cell
      carcinoma of the head and neck region.
AB  - Over the past decade important advances have been made in the treatment of
      locally advanced squamous cell carcinoma of the head and neck (SCCHN).
      Traditionally, chemotherapy has been incorporated in the treatment of SCCHN
      either before local treatment as induction, concomitantly with radiation, or
      following local treatment as adjuvant therapy. A number of randomized trials and
      meta-analyses have demonstrated that induction chemotherapy (usually based on the
      combination of cisplatin and 5-d continuous infusion of fluorouracil) followed by
      local treatment or concomitant chemoradiotherapy (CCRT) each prolongs survival
      and results in organ preservation in a significant number of patients. Survival
      rates appear to be higher when CCRT with cisplatin is used. Furthermore,
      accelerated fractionation radiation regimens have shown improved local control
      rates in randomized trials. Recently, new therapeutic strategies such as
      induction chemotherapy followed by CCRT or the incorporation of newer agents such
      as taxanes are under intense investigation and preliminary results are promising.
      Advances in molecular biology have led to the elucidation of molecular mechanisms
      that initiate and maintain the malignant phenotype in SCCHN. The identification
      of molecular targets has revolutionized our approach to cancer therapy and
      resulted in the introduction of novel targeted therapies. Cyclin-dependent
      kinases, the tumor suppressor p53 gene, and epidermal growth factor receptor are
      some of the molecular targets of such therapies in patients with SCCHN.

PMID- 16645226
TI  - T-cell prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive post-thymic
      malignancy with poor response to conventional treatment and short survival. It
      can readily be distinguished from other T-cell leukemias on the basis of the
      distinctive morphology, immunophenotype, and cytogenetics. Consistent chromosomal
      translocations involving the T-cell receptor gene and one of two protooncogenes
      (TCL-1 and MTCP-1) are seen in the majority of cases and are likely to be
      involved in the pathogenesis of the disorder. The CD52 antigen is expressed at
      high density on the malignant T-cells and therapy with alemtuzumab, a humanized
      IgG1 antibody that targets this antigen, has produced promising results. In
      relapsed/refractory patients overall and complete response rates have been seen
      in up to 76% and 60%, respectively. In previously untreated patients, complete
      remission rates of 100% have been reported. These responses are durable and
      translate into improved survival for responders. However, relapse is inevitable
      and strategies using both autologous and allogeneic stem cell transplantation are
      currently being explored. Additional clinical trials are investigating the use of
      alemtuzumabin combinations with chemotherapy, either concurrent or sequential. In
      the future we hope to have a betterunderstanding of how best to integrate these
      therapeutic approaches to further prolong survival for patients with T-PLL.

PMID- 16645227
TI  - The diagnostic plot: a concept for identifying different states of iron
      deficiency and monitoring the response to epoetin therapy.
AB  - Iron balance is regulated by the rate of erythropoiesis and the size of the iron
      stores. Anemia that accompanies infection, inflammation, and cancer (anemia of
      chronic disease) features normal or increased iron stores, although patients may
      have functional iron deficiency, namely, an imbalance between iron requirements
      of the erythroid marrow and the actual supply. The proportion of hypochromic red
      cells and the hemoglobin content of reticulocytes are direct indicators of
      functional iron deficiency. Biochemical markers, especially the soluble
      transferrin receptor/log ferritin ratio (ferritin index), are useful indicators
      of the iron supply to erythropoiesis. The relationship between functional iron
      deficiency (reticulocyte hemoglobin content) and iron supply to erythropoiesis
      (ferritin index) can be described in a diagnostic plot. In normoproliferative and
      hypoproliferative erythropoiesis, the plot allows the differentiation of classic
      iron deficiency from anemia of chronic disease and the combined state of
      functional iron deficiency with anemia of chronic disease. The therapeutic
      implications of the plot are to differentiate patients into those who should be
      administered iron supplements, epoetin, or a combination of epoetin and iron. In
      patients receiving epoetin therapy, the plot is an important tool for monitoring
      erythropoietic activity, functional iron deficiency, and adequate iron stores for
      new red cell production. Enhanced erythropoiesis is reflected quantitatively by
      the ferritin index vector. A transgression of the 1.5 (3.2) cut-off value for the
      ferritin index indicates that extra doses of iron need to be administered to
      increase the body's iron stores. A lack of increase or a reticulocyte hemoglobin
      content below 28 picograms indicates functional iron deficiency. The diagnostic
      plot is a model for differentiating iron-deficient states and predicting those
      patients who will respond to epoetin therapy.

PMID- 16645228
TI  - Impact of growth factors in the regulation of apoptosis in low-risk
      myelodysplastic syndromes.
AB  - Increased apoptosis of hematopoietic progenitors is a hallmark of myelodysplastic
      syndromes (MDS) and results in ineffective hematopoiesis. Erythroid apoptosis is
      thought to be the main mechanism underlying the severe anemia observed in the low
      risk subgroups, refractory anemia (RA) and RA with ringed sideroblasts (RARS).
      Treatment with erythropoietin (Epo) alone or in combination with granulocyte
      colony-stimulating factor (G-CSF) may significantly improve anemia and reduce
      bone marrow apoptosis. A synergistic effect between Epo and G-CSF has been
      observed in the clinic, in particular in RARS. However, the molecular mechanisms
      beyond the anti-apoptotic effect of these growth factors have not been fully
      understood. This paper outlines the potential mechanisms underlying the augmented
      apoptosis during the erythroid differentiation in low-risk MDS as well as the
      anti-apoptotic effect of the growth factors.

PMID- 16645229
TI  - Jaw complications associated with bisphosphonate use in patients with plasma cell
      dyscrasias.
AB  - Osteonecrosis of the jaw has been linked with bisphosphonate use in breast cancer
      and multiple myeloma patients. We report 17 cases of patients with plasma cell
      dyscrasia being treated with bisphosphonate who developed
      osteonecrosis/osteomyelitis of the jaw. Seventeen patients evaluated at our
      institution between 1998 and 2005 are reported. All were being treated with
      bisphosphonates for a median of 5 mo prior to the onset of jaw symptoms. Sixteen
      of the 17 patients are 51 yr or older. None of the patients had been irradiated
      in the jaw nor had obvious osseous manifestation of multiple myeloma in the jaw.
      Thirteen patients were receiving zoledronic acid and four patients were receiving
      pamidronate at the onset of jaw symptoms. Six of the 17 did receive both agents
      at some time and all of these individuals were receiving zoledronic acid at
      diagnosis. Microorganisms were isolated in 7/17 patients with the most common
      organism being actinomycosis. We have initiated the following guidelines in an
      effort to ameliorate the incidence of this complication. Patients should have a
      full dental examination at the time of diagnosis of the plasma cell dyscrasia
      especially if bisphosphonates are to be considered as part of the therapy. In
      addition, bisphosphonates are held for a period of 3 mo prior to invasive dental
      procedures to allow for the osteoclastic recovery, therefore enhanced debris
      removal and lessening the chance of creating a fertile bacterial medium.
      Following the dental procedure we would re-introduce bisphosphonates only after
      the healing process is complete. Finally, multiple myeloma patients diagnosed
      with jaw osteonecrosis probably have a concurrent infection and should be
      aggressively treated with antibiotics.

PMID- 16645230
TI  - Epiphora (excessive tearing) and other ocular manifestations related to weekly
      docetaxel: underestimated dose-limiting toxicity.
AB  - PURPOSE: Epiphora due to canalicular stenosis is a recently described side effect
      of weekly docetaxel. We prospectively evaluated the incidence of this
      complication and other ocular manifestations in patients treated at our medical
      center. PATIENTS AND METHODS: Twenty-one consecutive patients (breast cancer: 14;
      metastatic non-small cell lung cancer: 6; metastatic nasopharyngeal carcinoma: 1)
      (female/male: 14/7; age range: 34-78 yr) were treated with weekly docetaxel (35
      mg/m2/wk iv for 6 wk, cycles repeated every 49 d). A standard questionnaire
      regarding epiphora was completed before each dose of docetaxel. Patients who
      complained of excessive tearing underwent a thorough ophthalmologic evaluation
      before receiving the next dose. RESULTS: Epiphora due to stenosis of the lacrimal
      puncti and canaliculi developed in seven (33%) patients following a cumulative
      dose of 208-645 mg/m2 (median: 400 mg/m2). Two patients developed complete
      canalicular stenosis requiring surgery. Epiphora was accompanied by madarosis and
      ectodermalization of the palpebral and bulbar conjunctiva, complete in five
      patients. Treatment was discontinued due to epiphora in two (10%) patients. After
      a median follow-up of 11 mo, four patients still had epiphora. CONCLUSION:
      Epiphora due to canalicular stenosis is a frequent complication of weekly
      docetaxel and might be dose limiting. Irreversible damage requiring surgical
      intervention may develop despite close monitoring.

PMID- 16645231
TI  - Contribution of the MDRD equation and of cystatin C for renal function estimates
      in cancer patients.
AB  - BACKGROUND: Serum creatinine (SCr) and Cockcroft-Gault creatinine clearance (CG
      CrCL) are used to estimate glomerular filtration rate (GFR). Other markers have
      been proposed including serum cystatin C (cysC) and the Modification of Diet in
      Renal Disease (MDRD) study equation. PATIENTS AND METHODS: We have compared the
      diagnostic performances of SCr, cysC, CG CrCL, and the MDRD equation in 144
      cancer patients. For reference we used either the measured or the predicted
      carboplatin clearance, which is around the GFR + 25 mL/min. RESULTS: CysC was
      more sensitive than SCr (70.1% vs 13.4%) but was not very specific (61% for a cut
      off = 0.95 mL). CysC values were higher in 40 cancer patients vs 40 healthy
      controls with a similar and normal mean CG CrCL (1.08 vs 0.71 mg/L; p < 0.001).
      CG and the MDRD equations gave similar values for Pearson's coefficient, ROC-plot
      AUC, and precision, except for patients with poor general status, where the MDRD
      equation was better (MAPE: 12.4% vs 19.6%, p < 0.001; R: 0.908 vs 0.813).
      CONCLUSIONS: In cancer patients, cysC is a more sensitive indicator of the
      glomerular filtration rate than SCr, but its diagnostic performance is lower than
      for CG CrCL. There may be no advantage in replacing the CG equation by the MDRD
      equation except for patients with severe malnutrition and/or inflammation.

PMID- 16645232
TI  - Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic
      radiotherapy.
AB  - PURPOSE: Radiation pneumonitis (RP) is a serious complication in patients
      undergoing thoracic radiotherapy (TRT). Serum KL-6 and SP-D have been shown to
      increase in several kinds of interstitial pneumonia. To evaluate their clinical
      usefulness in detecting RP, we serially measured them in patients receiving TRT.
      MATERIALS AND METHODS: Thirty-nine patients, who received TRT for lung cancer
      between July 1999 and April 2004, were prospectively studied. Serum levels of KL
      6 and SP-D were measured using enzyme-linked immunosorbent assays. Patients were
      followed up until August 2004 or their deaths. RESULTS: During the period, RP
      occurred in 19 patients. In five patients with diffuse RP extended outside the
      radiation field, serum KL-6 levels increased, reaching more than 1,000 U/mL.
      Serum KL-6 levels at 40 Gy in patients who developed RP were higher than those
      without it (p = 0.0363, Mann-Whitney U test). In addition, serum KL-6 levels at
      40 Gy in patients who developed RP were higher than those of pretreatment (p =
      0.0126, Wilcoxon signed rank test). On the other hand, there were no statistical
      differences between sp-d at 40 Gy and those before TRT (P = 0.1165). CONCLUSIONS:
      Increased KL-6 at 40 Gy compared with those before treatment in patients
      undergoing TRT may be of clinical significance. KL-6 proved to be a useful
      indicator for estimating RP, while usefulness of SP-D was not confirmed in this
      study.

PMID- 16645234
TI  - Advanced colon cancer: antiprogressive immunotherapy using an autologous
      hemoderivative.
AB  - INTRODUCTION: Advanced colon cancer patients, acquired-chemotherapy resistant and
      in progression, are therapeutically terminal. We tested a recently described
      medical procedure using a thermostable autologous hemoderivative purported to
      inhibit tumor growth possibly through an immunological mechanism of action.
      PATIENTS AND METHODS: Metastatic colon cancer patients chemotherapy-resistant,
      high CEA plasma levels, in progression, were 2-group randomized. Group 1 received
      the test procedure and Group 2 adequate control measures. During an 8-mo follow
      up period (n = 101), tumor growth, number of cases attaining clinical
      nonprogressive status, and mortality were assessed monthly. Immunological effect
      was assessed by delayed-type hypersensitivity test and lymphocyte proliferation
      assay. Responding-tumors histopathologies were studied. RESULTS AND DISCUSSION:
      In a significant number of cases, the test procedure promoted inhibition of tumor
      growth, nonprogressive disease status, and lower cumulative mortality. These
      clinical results were associated with polyvalent immunization against several
      tested antigens: the hemoderivative used for treatment, the blood tumor markers,
      and the regulatory lymphocyte population (CD4+CD25+). Interference with this
      regulatory activity could explain the selective autoimmunity suggested by the
      histopathology findings in responding tumors. CONCLUSION: The autologous
      hemoderivative tested is antigenically polyvalent and promotes a polytargeted
      immune response associated with a tumor antiprogressive effect, consequently,
      acting as an autologous hemoderivative cancer vaccine.

PMID- 16645233
TI  - Ki-67 proliferative marker in lymph node aspirates of patients with non-Hodgkin's
      lymphoma.
AB  - Proliferative activity of lymphoma cells was tested by immunocytochemical
      staining with Ki-67 monoclonal antibody in 63 aspirates of peripheral lymph nodes
      sampled from patients suffering from non-Hodgkin's lymphoma. Referring to the
      dominant cell population in nodal aspirates, a rising trend of Ki-67
      proliferative marker was noted from the small cells (X = 13.20) and small cells
      with notched nucleus (X = 43.52) and large cells (X = 79.47) with histopathologic
      equivalents corresponding to aggressive lymphoma. Statistical testing of the
      difference in the Ki-67 proliferative marker against demographic and clinical
      laboratory characteristics of the studied patients revealed the levels of
      significance for the performance status, bone marrow infiltration, and albumin
      serum value. Correlation of cytomorphological and immunocytochemical results was
      tested against International Prognostic Index (IPI). Statistically significant
      correlation of Ki-67 with cytomorphology and REAL-immunocytochemical
      classification of lymphoma was confirmed, but not with the IPI index. In order to
      determine the prognostic importance of Ki-67 marker, the patients were classified
      into those with low Ki-67 (<20% of proliferating cells), mean proliferation index
      Ki-67 (range 20-59%), and high proliferative index Ki-67 (positive in over 60% of
      lymphoma cells). Testing Ki-67 with survival we have found that the low
      proliferative index was associated with the longest survival, median about 36 mo;
      for proliferative marker values ranging between 20 and 59%, the median survival
      was 30.4 mo; and survival of patients with the high proliferative index was only
      12.9 mo.

PMID- 16645235
TI  - In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline,
      arginine, and green tea extract on human fibrosarcoma cells HT-1080.
AB  - Current treatment of fibrosarcoma, an aggressive cancer of the connective tissue,
      is generally associated with poor prognosis. Matrix metalloproteinases (MMPs),
      vascular endothelial growth factor (VEGF), and constituents of the extracellular
      matrix (ECM), such as fibronectin, play a critical role in angiogenesis and
      underlie neoplastic invasion and metastasis. This and anticancer properties of
      lysine, proline, arginine, ascorbic acid, and green tea extract (NM) prompted us
      to investigate the effect of these nutrients in vitro on human fibrosarcoma cells
      HT-1080 by measuring cell proliferation, modulation of MMP-2 and MMP-9, and
      invasive potential. In vivo, we studied the growth of human fibrosarcoma HT-1080
      cells in athymic nude mice and the expression of MMPs and VEGF. Cell
      proliferation was evaluated by MTT assay, MMP expression by gelatinase
      zymography, and invasion through Matrigel and migration by scratch assay. Tumors
      were excised, weighed, and processed for histology in both the control and
      nutrient-supplemented groups. Results showed NM inhibited the growth and reduced
      the size of tumors in nude mice; decreased MMP-9 and VEGF secretion was found in
      the supplemented group tissues. NM inhibited invasion through Matrigel and
      migration with total inhibition at 1,000 microg/mL. These results offer promise
      in the therapeutic use of the nutrient mixture of lysine, proline, arginine,
      ascorbic acid, and green tea extract tested in the treatment of fibrosarcoma.

PMID- 16645236
TI  - The carcinogenic role of oncogenic HPV and p53 gene mutation in cervical
      adenocarcinomas.
AB  - Thirty tumors were collected from our archive of cervical adenocarcinomas. They
      were examined with respect to the content of oncogenic HPV and presence of
      mutations in the p53 gene exons 5 through 8. Furthermore, available clinical
      information on the cases was reviewed. For the detection of p53 gene and presence
      of oncogenic HPV, PCR followed by direct sequence analysis of the amplified DNA
      was employed. Seventeen tumors were identified as HPV-positive, comprising both
      HPV types 18 and 16. Six cases showed a p53 gene mutation, of which five were of
      the missence and one of the silent type. No statistical correlation between the
      occurrence of oncogenic HPV and presence of p53 gene mutation (p = 0.67) was
      recorded. Among the tumors with p53 gene mutation, three were HPV-positive and
      three were HPV-negative. The determination of p53 gene mutations was not related
      to clinical findings such as the stage of the tumor or presence of metastases of
      the lymph nodes. However, p53 gene mutations were somewhat more prevalent in low
      differentiated tumors (p < 0.02). The results indicate that oncogenic HPV and p53
      gene mutations have independent carcinogenic roles in cervical adenocarcinomas.

PMID- 16645237
TI  - Drug-induced hepatitis in a patient with malignant melanoma treated with
      interferon alfa 2b adjuvantly who had been administered gemfibrozil in therapy.
AB  - A well-known side effect of chemotherapy, covering a wide range of drugs, is drug
      induced hepatitis. We are reporting on a 61-yr-old female patient whose malignant
      melanoma had been surgically removed, and on whom adjuvant therapy with
      interferon alfa 2b was initiated. The patient had mild hyperlipidemia, of which
      she had been aware for several years, but which had gone untreated with medicinal
      intervention. After the patient was started on interferon alfa therapy,
      continuously increasing values of triglyceride were measured. Therefore, 3 mo
      after the introduction of adjuvant therapy, gemfibrozil was prescribed at a dose
      of 600 mg per day. Within a few days after the patient had been taking this
      combined therapy, the clinical and laboratory values of drug-induced hepatitis
      developed. Soon after discontinuance of treatment by both drugs, the signs and
      symptoms of hepatitis disappeared. Adjuvant interferon therapy was not continued
      afterward owing to the patient's wish. We do not know if the hepatitis was the
      side effect to gemfibrozil alone, or the side effect was a result of an
      interaction between the two drugs. As far as we could find, this is the first
      case report of possible negative interaction between interferon alfa 2b and
      gemfibrozil. Our intention in this article is to point out that prescription of
      any drugs, especially new ones, should be balanced and carefully monitored
      because of possible side effects.

PMID- 16645238
TI  - Improvement of chronic pulmonary graft-vs-host disease manifesting as
      bronchiolitis obliterans organizing pneumonia following extracorporeal
      photopheresis.
AB  - Despite use of combined immunosuppressive agents, prognosis of patients
      developing pulmonary manifestations of chronic graft-vs-host disease (cGVHD)
      following allogeneic stem cell transplantation (SCT) still remains poor. We
      present a male patient who developed pulmonary cGVHD in the form of bronchiolitis
      obliterans organizing pneumonia (BOOP) following allogeneic SCT for acute
      myelogenous leukemia. The patient developed progressive course despite use of a
      combination of immunosuppressive agents including high-dose prednisone,
      cyclosporin-A, and mycophenolate mofetil in addition to steroid-related
      complications. A remarkable clinical response to extracorporeal photopheresis
      (ECP) was observed, allowing minimization of immunosuppressive therapy and
      discontinuation of cyclosporin-A. Pulmonary functions and carbon monoxide
      diffusion capacity (DLCO) gradually improved and stabilized, but did not return
      to pretransplant baseline levels.

PMID- 16645239
TI  - Unusual IgD+/CD38-follicular lymphoma with leukemic presentation.
AB  - Follicular lymphoma (FL) is a low-grade lymphoma, with rare presentation of
      leukemic phase in peripheral blood at the diagnosis. We describe a 49-yr-old
      woman who developed leukemic phase of FL in a 3 mo period after histological
      diagnosis of peripheral lymph node. To confirm the final diagnosis, flow
      cytometry (FCM) of peripheral blood, nested PCR with bcl-2 rearrangement, and
      cytogenetic analysis of peripheral blood and bone marrow cells were done.
      Lymphoma cells were negative for CD38 and expressed monoclonal surface
      immunoglobulins with relatively strong and "bright" IgD and "dim" kappa-chain by
      FCM analysis. Although the patient presented with generalized lymphadenopathy,
      massive peripheral blood and bone marrow involvement, she achieved complete
      clinical response after first-line chemotherapy COP and rituximab. She is still
      in a good condition with follow up over 2 yr.

PMID- 16645240
TI  - Alemtuzumab therapy for severe autoimmune hemolysis in a patient with B-cell
      chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is the most common cause of
      autoimmune hemolytic anemia (AIHA), and a subgroup of these patients who develop
      both these conditions fail to respond to corticosteroids, cytotoxic drugs,
      splenectomy, and iv immunoglobulins. Alemtuzumab is a humanized anti-CD52
      monoclonal antibody that is an effective therapy for B-CLL, mycosis fungoides,
      and T-cell prolymphocytic leukemia. Here we present a case report of a 78-yr-old
      woman with B-CLL and progressive life-threatening AIHA with hemoglobin count 5.5
      g/dL following fludarabine treatment, who was treated successfully with
      alemtuzumab. The anemia was completely reversed and hemoglobin count remains at
      14 g/dL after 15 mo of unmaintained follow-up. No infectious complications were
      noted during or after alemtuzumab therapy. We conclude that alemtuzumab may be
      indicated for the treatment of AIHA in B-CLL patients who have failed other
      treatments.

PMID- 16645241
TI  - Peripheral T-cell lymphoma and Job's syndrome: a rare association.
AB  - Job's syndrome or hyper-immunoglobulin E syndrome is a primary immunodeficiency
      characterized by recurrent staphylococcal abscesses and markedly elevated serum
      immunoglobulin E concentrations. Here we report a case of a woman with hyper
      immunoglobulin E syndrome with a diagnosis of peripheral T-cell lymphoma, and we
      review the pertinent literature.

PMID- 16645242
TI  - Travel-associated legionnaires' disease in Europe: 2004.
AB  - Six hundred and fifty five cases of travel-associated legionnaires' disease with
      onset in 2004 have been reported to the EWGLINET surveillance scheme by 25
      countries. A total of 84.9% of cases were diagnosed by the urinary antigen test,
      and 37 cultures were obtained. Thirty seven deaths were reported, giving a case
      fatality rate of 5.6%. Eighty six new clusters were detected, 45% of which would
      not have been detected without the EWGLINET scheme. Ninety four accommodation
      sites were investigated and the names of four sites were published on the EWGLI
      website. Fifteen sites were associated with additional cases after a report was
      received to say that investigations and control measures had been satisfactorily
      carried out. Further improvements could be made in the data collected on deaths
      due to travel-associated legionnaires' disease, and on the number of samples
      taken for culture throughout Europe.

PMID- 16645244
TI  - Two outbreaks of measles in Germany 2005.
AB  - Measles re-emerged in some counties in Germany in 2005, despite increasing
      vaccination coverage rates in children at school entry in recent years, which had
      led to decreasing incidence (with the lowest incidence ever recorded, 0.2 cases
      per 100,000 inhabitants in 2004). Regional outbreaks have been detected by the
      mandatory reporting system in the states of Hesse and Bavaria. Although both
      outbreaks led to similar incidences in the affected areas (14 and 12 cases
      respectively per 100,000 inhabitants) they differed in age distribution,
      transmission patterns and measles virus genotype. In Hesse, 223 cases were
      submitted, from which 160 belonged to 41 clusters mainly defined by ,000).
      Results of measles virus diagnosis showed genotype D4 and identical nucleotide
      sequences for all analysed cases from Hesse. In Bavaria, 279 cases were
      submitted, most of which had occurred in schools and preschool facilities. Age
      specific attack rate was highest in children aged between 5-9 years (129 per
      100,000). Laboratory diagnosed viruses were identified as genotype D6 and were
      identical at the nucleotide level. In both outbreaks the vast majority of cases
      (95% in Hesse and 98% in Bavaria) were in unvaccinated children, but vaccination
      coverage differed in the affected areas and was slightly lower in Bavaria than in
      Hesse. Local accumulation of unvaccinated children and their concentration in
      schools and kindergarten preceded the outbreak in Bavaria. Despite high average
      vaccination coverage levels, local variations may lead to regionally limited
      outbreaks.

PMID- 16645245
TI  - SurvNet@RKI--a multistate electronic reporting system for communicable diseases.
AB  - In 2001 Germany implemented a new electronic reporting system for surveillance of
      notifiable infectious diseases (SurvNet@RKI). The system is currently being used
      in all 431 local health departments (LHD), the 16 state health departments (SHD)
      and the Robert Koch-Institut (RKI), the national agency for infectious disease
      epidemiology. The SurvNet@RKI software is written in MS Access 97 and Visual
      Basic and it supports MS Access as well as MS SQL Server database management
      systems as a back-end. The database is designed as a distributed, dynamic
      database for 73 reporting categories with more than 600 fields and about 7000
      predefined entry values. An integrated version management system documents
      deletion, undeletion, completion and correction of cases at any time and entry
      level and allows reproduction of previously conducted queries. Integrated
      algorithms and help functions support data quality and the application of case
      definitions. RKI makes the system available to all LHDs and SHDs free of charge.
      RKI receives an average of 300,000 case reports and 6240 outbreak reports per
      year through this system. A public web-based query interface, SurvStat@RKI,
      assures extensive and timely publication of the data. During the 5 years that
      SurvNet@RKI has been running in all LHDs and SHDs in Germany it has coped well
      with a complex federal structure which makes this system particularly attractive
      to multinational surveillance networks. The system is currently being migrated to
      Microsoft C#/.NET and transport formats in XML. Based on our experiences, we
      provide recommendations for the design and implementation of national or
      international electronic surveillance systems.

PMID- 16645246
TI  - Outbreak of E. coli O157 infection in the south west of the UK: risks from
      streams crossing seaside beaches.
AB  - In August 2004 seven cases of Escherichia coli O157 infection were identified in
      children on holiday in Cornwall, southwest England, all of whom had stayed at
      different sites in the area. Isolates from all seven cases were confirmed as E.
      coli serogroup O157 phage type 21/28. We carried out a case-control study among
      holidaymakers who visited the beach. A standardised questionnaire was
      administered by telephone to parents. They were asked where on the beach the
      children had played, whether they had had contact with the stream that flowed
      across the beach, and about their use of food outlets and sources of food eaten.
      Cases were more likely to have played in the stream than controls (OR [1.72-
      undefined]). The time spent in the stream by cases was twice spent there by
      controls. Cases and controls were equally exposed to other suspected risk
      factors. PFGE profiles for all the cases were indistinguishable. Increased
      numbers of coliforms were found in the stream prior to the outbreak. Cattle were
      found grazing upstream. We suggest that the vehicle of infection for an outbreak
      of acute gastrointestinal illness caused by E. coli O157 was a contaminated
      freshwater stream flowing across a seaside beach. The onset dates were consistent
      with a point source. Heavy rainfall in the days preceding the outbreak might have
      lead to faeces from the cattle potentially contaminated by E. coli O157
      contaminating the stream, thereby leading to the outbreak. Control measures
      included fencing off the part of the stream in which children played, and putting
      up warning signs around the beach.

PMID- 16645247
TI  - Cryptosporidium outbreak linked to interactive water feature, UK: importance of
      guidelines.
AB  - A need for national guidelines relating to interactive water features was
      highlighted following three outbreaks of cryptosporidiosis in the United Kingdom,
      all of which were related to public water features. In August 2003 the Health
      Protection Agency South West of England was notified of an outbreak of
      cryptosporidiosis associated with an interactive water feature designed for water
      play within an adventure park. The water feature was implicated following samples
      with a high coliform count and the presence of faecal coliforms. A case was
      defined as any child (younger than 16 years of age) who had visited the park
      during August and who subsequently had gastrointestinal symptoms and a faecal
      sample positive for cryptosporidium. Seventy one children were identified in the
      cohort. This outbreak of cryptosporidiosis was characterised by a very high
      attack rate (89%), relatively severe in duration (median 8 days) and had a
      relatively high hospital admission (16% of cases). The epidemic curve was
      consistent with a point source of infection, which corresponded to the date 80%
      of the cohort visited the park. This outbreak has similarities to two other
      cryptosporidiosis outbreaks reported in England in 2003 that involved public
      water features. These outbreaks raise issues about the operation and maintenance
      of water-based recreational attractions that very often involve children. The
      paper reflects on the basic control measures that can be taken and highlights the
      need for guidelines, especially since such attractions are becoming increasingly
      common. The Pool Water Treatment Advisory Group in United Kingdom has now
      produced guidelines.

PMID- 16645248
TI  - Infection risks from water in natural and man-made environments.

PMID- 16645249
TI  - The ID23-1 structural biology beamline at the ESRF.
AB  - The demand for access to macromolecular crystallography synchrotron beam time
      continues to increase. To meet this demand the ESRF has constructed a dual
      station beamline using a canted undulator system as the X-ray source. The first
      phase of the beamline to be constructed is ID23-1, a tunable MAD-capable station
      with a mini-focus X-ray beam. The beamline makes use of well characterized
      optical elements: a channel-cut monochromator with a high-precision toroidal
      mirror to focus the X-ray beam. The beamline has been conceived with the aim of
      providing high levels of automation to create an industrial-like environment for
      protein crystallography. A new software suite has been developed to permit
      reliable easy operation for the beamline users and beamline staff. High levels of
      diagnostics are built in to allow rapid trouble-shooting. These developments are
      now being exported to the ESRF macromolecular crystallography beamline complex
      and have been made in a modular fashion to facilitate transportability to other
      synchrotrons.

PMID- 16645250
TI  - On the feasibility of large-aperture Fresnel lenses for the microfocusing of hard
      X-rays.
AB  - Like visible light, X-rays can also be focused by refraction in transmission
      lenses. For visible light this requires convex lenses while for X-rays one needs
      to use concave lenses instead. Both lens types can be lightened by the material
      removal strategy introduced by Fresnel, which results in a lens subdivided into
      zones. Until now, for the focusing of X-rays, stacks of standard lenses and of
      Fresnel lenses have mostly been produced. The first are dubbed compound
      refractive lenses, abbreviated as CRL. State-of-the-art systems of this kind now
      achieve almost theoretical performance for the focus size and the transmission.
      On the other hand, the latter Fresnel systems, which promise to provide larger
      apertures, are still in their infancy. This report discusses systematically the
      properties of two possible schemes for their realisation. It then compares the
      optimized apertures of these two schemes with those for CRLs. The best Fresnel
      lenses in this study are found to provide experimentally more than 50% of the
      expected refraction efficiency at 8.5 keV photon energy. The photon flux in their
      focus is then almost identical to that of perfect Be CRLs with the same focal
      length. This report will also interpret experimental data reported previously for
      other Fresnel lenses.

PMID- 16645251
TI  - Optimizing the signal-to-noise ratio for X-ray photon correlation spectroscopy.
AB  - An analysis is presented of how to optimize the experimental beamline
      configuration for achieving the best possible signal-to-noise ratio (SNR) in X
      ray photon correlation spectroscopy experiments using area detectors. It is shown
      that there exists an optimum detector distance; namely, the highest SNR is
      achieved by matching the angular pixel size with the angular source size. Binning
      several pixels together can increase the SNR by permitting to match the shape of
      a detector pixel to the shape of the source. It is also shown that collimating
      slits several times wider than the effective transverse coherence length are
      optimal; further, it is demonstrated that the energy dependence of the SNR is
      dictated by the energy dependence of detector efficiency and source brilliance.
      Ultimately the effects of focusing and low longitudinal coherence are discussed.

PMID- 16645252
TI  - Evaluation of imaging performance of a taper optics CCD; FReLoN' camera designed
      for medical imaging.
AB  - The purpose of this work was to assess the imaging performance of an indirect
      conversion detector (taper optics CCD; FReLoN' camera) in terms of the modulation
      transfer function (MTF), normalized noise power spectrum (NNPS) and detective
      quantum efficiency (DQE). Measurements were made with a synchrotron radiation
      laminar beam at various monochromatic energies in the 20-51.5 keV range for a
      gadolinium-based fluorescent screen varying in thickness; data acquisition and
      analysis were made by adapting to this beam geometry protocols used for
      conventional cone beams. The pre-sampled MTFs of the systems were measured using
      an edge method. The NNPS of the systems were determined for a range of exposure
      levels by two-dimensional Fourier analysis of uniformly exposed radiographs. The
      DQEs were assessed from the measured MTF, NNPS, exposure and incoming number of
      photons. The MTF, for a given screen, was found to be almost energy independent
      and, for a given energy, higher for the thinnest screen. At 33 keV and for the 40
      (100) microm screen, at 10% the MTF is 9.2 (8.6) line-pairs mm(-1). The NNPS was
      found to be different in the two analyzed directions in relation to frequency.
      Highest DQE values were found for the combination 100 microm and 25 keV (0.5); it
      was still equal to 0.4 at 51.5 keV (above the gadolinium K-edge). The DQE is
      limited by the phosphor screen conversion yield and by the CCD efficiency. At the
      end of the manuscript the results of the FReLoN characterization and those from a
      selected number of detectors presented in the literature are compared.

PMID- 16645253
TI  - X-ray diffractometer combining synchrotron radiation and pulsed magnetic fields
      up to 40 T.
AB  - A synchrotron X-ray diffractometer incorporating a pulsed field magnet for high
      fields up to 40 T has been developed and a detailed description of this
      instrument is reported. The pulsed field magnet is composed of two coaxial coils
      with a gap of 3 mm at the mid-plane for passage of the X-rays. The pixel detector
      PILATUS 100K is used to store the diffracted X-rays. As a test of this
      instrument, X-ray diffraction by a powder sample of the antiferromagnet CoO is
      measured below the Neel temperature. A field-dependent lattice distortion of CoO
      due to magnetostriction is observed up to 38 T.

PMID- 16645254
TI  - Temperature-resolved in situ X-ray absorption spectroscopic study on the
      reduction of nanostructured Fe(2)O(3) within the pore system of mesoporous carbon
      CMK-1.
AB  - Results of in situ X-ray absorption spectroscopy experiments on the reduction of
      thin-layered nanostructured X-ray amorphous iron(III) oxides inside the pore
      system of mesoporous carbon CMK-1 are presented. These in situ measurements were
      carried out using 4% hydrogen in nitrogen as reduction gas over a 300-1000 K
      temperature range. The thermochemical behaviour of the nanostructured materials
      was compared with that of the bulk phases. The spectra series examined by factor
      analysis gave a good insight into the reduction products of iron oxide
      nanoparticles occurring in mesoporous carbon CMK-1.

PMID- 16645255
TI  - Nearly perfect large-area quartz: 4 meV resolution for 10 keV photons over 10
      cm(2).
AB  - The perfection of two commercial top-grade quartz crystal wafers has been
      investigated using Bragg reflection at theta(B)=89.77 degrees of a 2.0 meV
      bandwidth beam of 9.979 keV X-rays by the (7?bar4?bar34) lattice planes.
      Topographic images show small defect concentrations (<or=5 cm(-2)). Energy scan
      widths are below 3 meV over 8 mm x 8 mm areas and 4 meV over the whole wafer (
      approximately 11 cm(2)). This suggests that quartz can be a useful optical
      material.

PMID- 16645256
TI  - High-resolution powder diffraction study of purple membrane with a large Guinier
      type camera.
AB  - X-ray diffraction patterns from a film of oriented purple membranes, which
      comprise two-dimensional crystals of bacteriorhodopsin (BR) trimers, were
      recorded with a 1 m-pathlength Guinier-type camera at SPring-8 BL40B2. A well
      focused X-ray beam and a camera with a high angular resolution of 0.024 degrees
      enabled a powder diffraction profile with very sharp and well separated peaks to
      be obtained up to a resolution of 2.3 A. Using integrated diffraction intensities
      up to a Bragg spacing of 4.2 A, a cluster of bulky amino acid residues and the
      head group of the BR chromophore are apparent in the electron density map
      projected along the membrane normal. Thus, a combination of synchrotron X-rays
      and large Guinier camera can be used for analyzing the conformational changes of
      BR in the intact state. In addition, the method might be extended to the
      structural analysis of film materials composed of two-dimensional arrays of
      nanoparticles.

PMID- 16645257
TI  - Comments on: A new model for statistical error analysis in XAS: about the
      distribution function of the absorption coefficient by E. Curis & S. Benazeth
      (2001). J. Synchrotron Rad.8, 264-266.

PMID- 16645262
TI  - Angiotensin-converting enzyme gene polymorphism in children with idiopathic
      nephrotic syndrome.
AB  - AIMS: To investigate the genetic polymorphism of angiotensin-converting enzyme
      (ACE) insertion/deletion (I/D) in children with idiopathic nephrotic syndrome
      (INS), as well as its relationship with patient's clinical response to steroid
      therapy. METHODS: Fifty-nine patients with INS were recruited and divided into 2
      groups according to their clinical response to steroids: steroid-sensitive (SS)
      with 19 patients and non-SS with 40 patients, which was further divided into
      steroid-dependent (SD) and steroid-resistant (SR) groups with 35 and 5 patients,
      respectively. Seventy-nine children without previous renal diseases and negative
      proteinuria were enrolled as a control group. The genotypes for ACE I/D
      polymorphism, including DD, ID, and II, were analyzed. RESULTS: The distribution
      of ACE DD, ID, and II genotypes in INS patients were 52.5, 10.2 and 37.3%,
      respectively; the corresponding numbers for the control group were 2.5, 25.3 and
      72.2%, respectively. Patients with INS had a significantly higher percentage of
      DD genotype (p <0.001) than the control group. This higher incidence of the DD
      genotype was observed in both the SS and non-SS groups. A higher percentage of
      the DD genotype in the non-SS group and in the SD group as compared to the SS
      group (both p < 0.05) was also noted. CONCLUSION: Our data shows that INS is
      associated with a higher incidence of the DD genotype, especially in non-SS
      patients. This finding suggests that the DD genotype may be a risk factor for INS
      and play a role in the clinical response to steroids.

PMID- 16645263
TI  - Effect of cyclosporine a on glucose interstitial concentration in renal cortex
      and medulla from rats.
AB  - AIM: To standardize microdialysis in rat kidneys and address cyclosporine A (CsA)
      effects on renal cortex and medulla interstitial glucose. METHODS: Munich-Wistar
      rats were treated with vehicle or CsA (15 mg/kg/day) for 3 weeks. Glucose was
      assessed by spectrophotometry in dialysate samples from cortex, medulla and
      arterial plasma. Plasma insulin was measured by radioimmunoassay. Renal blood
      flow (RBF) was measured by Doppler ultrasound. Creatinine and urea were measured
      by spectrophotometry. RESULTS: CsA significantly increased the plasma levels of
      urea and creatinine (1.5 +/- 0.20 vs. 0.73 +/- 0.03 mg/dl in controls, p < 0.05).
      Medullary glucose in control was 44% lower than arterial glucose (56 +/- 6 vs.
      101 +/- 8 mg/dl, p < 0.05). At the same time, CsA increased arterial (163 +/- 35
      vs. 101 +/- 8 mg/dl in controls, p < 0.05) and medullary interstitial glucose
      (100 +/- 18 vs. 56 +/- 6 mg/dl in controls, p < 0.05), but did not affect
      cortical glucose (114 +/- 21 vs. 90 +/- 11 mg/dl in controls). These changes
      occurred in the presence of a decreased plasma insulin level (2.7 +/- 0.2 vs. 9.3
      +/- 0.4 microU/ml in controls, p < 0.05). The increment in medullary glucose in
      CsA group occurred despite a reduction in RBF (4.6 +/- 0.8 vs. 6.5 +/- 1.0
      ml/min/kidney in controls, p < 0.05). CONCLUSIONS: Microdialysis was an adequate
      tool to investigate in vivo regulation of renal glucose metabolism. Renal glucose
      uptake was dependent on medullary cells and CsA treatment induced diabetogenic
      effects on renal medulla in situ.

PMID- 16645264
TI  - Salt sensitivity and hypertension after menopause: role of nitric oxide and
      angiotensin II.
AB  - Hypertension is a major risk factor for cardiovascular disease and renal disease.
      After menopause, the incidence of hypertension increases in women to levels that
      equal or exceed that in men, suggesting a protective role of female sex hormones.
      Salt sensitivity of blood pressure is associated with an increased risk for
      development of hypertension and cardiovascular disease. We and others have
      demonstrated that after menopause, the prevalence of salt sensitivity increases,
      suggesting that female sex hormones influence renal sodium handling and blood
      pressure regulation. A homeostatic balance between the counteracting effects of
      nitric oxide (NO) and angiotensin (Ang) II on pressure natriuresis, renal
      hemodynamics, tubular sodium reabsorption, and oxidative stress plays an
      important role in modulating salt sensitivity as well as hypertensive end-organ
      injury. Estrogens modulate the activity and expression of NO and Ang II. We infer
      that after menopause, estrogen deficiency promotes an unbalance between NO and
      Ang II, resulting in disturbed renal sodium handling, oxidative stress, and
      hypertension, particularly in genetically prone women. A better understanding of
      the mechanisms underlying the development of postmenopausal hypertension and
      associated cardiovascular and renal diseases should provide insights into
      preventive and therapeutic strategies.

PMID- 16645265
TI  - Gene expression of the Na-Ca2+ exchanger, SERCA2a and calsequestrin after
      myocardial ischemia in the neonatal rabbit heart.
AB  - BACKGROUND: Neonatal hearts are less susceptible to developing myocardial
      dysfunction after hypoxia and/or ischemia than adult hearts. Differences in
      intracellular calcium homeostasis may be responsible for reduced calcium overload
      of the immature myocardium leading to the observed protection against ischemia.
      OBJECTIVE: To assess differences in baseline and post-ischemic gene expression of
      calcium handling proteins after ischemia in neonatal and adult rabbit hearts.
      METHODS: We used isolated antegrade perfused rabbit hearts (age 2 days, 28 days,
      n = 32), which were exposed to ischemia and hypothermia simulating myocardial
      stunning comparable to neonatal asphyxia. Gene and protein expression of the
      sodium-calcium exchanger (NCX), the sarco-endoplasmatic reticulum Ca2+-ATPase 2a
      (SERCA) and calsequestrin (CSQ) were measured using quantitative real-time PCR
      and Western blotting. RESULTS: After ischemia and reperfusion in neonatal and
      adult hearts, a significant decrease in myocardial performance was recorded. At
      the mRNA level, significant differences in the baseline expression of NCX, SERCA
      and CSQ between neonatal and adult hearts were observed. In neonatal post
      ischemic hearts, NCX and CSQ expression were significantly higher at the mRNA
      level than in controls. In contrast, SERCA expression remained unchanged in
      neonatal hearts and decreased in adult hearts compared to the non-ischemic
      controls. CONCLUSION: These findings suggest that changes in gene expression of
      calcium handling proteins may be involved in the different susceptibility of
      neonatal compared to adult hearts to developing myocardial dysfunction after
      ischemia.

PMID- 16645266
TI  - Elimination of piperacillin and tazobactam by renal replacement therapies with
      AN69 and polysulfone hemofilters: evaluation of the sieving coefficient.
AB  - BACKGROUND/AIM: Piperacillin-tazobactam is commonly used to treat infections in
      ICU patients. Controversial data have been published about the sieving/saturation
      coefficient (Sc/Sa) of piperacillin during continuous renal replacement therapies
      (CRRT). The objective was to evaluate the Sc/Sa of piperacillin-tazobactam during
      continuous venovenous hemofiltration (CVVH) and continuous venovenous
      hemodialysis (CVVHD) using AN69 and polysulfone. METHODS: Ringer lactate, BSA
      containing Ringer lactate and plasma were circulated at 150 ml/min. The
      ultrafiltrate/dialysis flow was kept at 1,500 ml/min. A bolus was injected and
      samples were taken. Drugs were measured using HPLC. Sc/Sa was calculated
      according to standard formula. RESULTS: Free passage of drugs through the
      membranes was reported with protein free solutions. In the presence of proteins
      the Sc/Sa lowered and correlated to protein free fraction. Polysulfone had a
      significantly higher permeability than AN69 during CVVH. CONCLUSION: Drug binding
      to albumin contributes to the decrease of the Sc/Sa of piperacillin but it does
      not completely justify the in vivo value obtained by some authors.

PMID- 16645267
TI  - Antiplatelet cilostazol is effective in the prevention of pneumonia in ischemic
      stroke patients in the chronic stage.
AB  - We have previously reported that the phosphodiesterase inhibitor cilostazol, an
      antiplatelet agent, is effective and safe for secondary prevention of recurrent
      cerebral infarction (Cilostazol Stroke Prevention Study; CSPS). We now report the
      efficacy of this drug in the prevention of pneumonia in the chronic stage of
      cerebral infarction as a part of our CSPS subgroup analysis. The analysis was
      conducted in 1,049 subjects; 524 in the cilostazol group and 525 in the placebo
      group. The incidences of pneumonia during the 3.3-year follow-up were 2.86% (15
      in 525 patients) in the placebo group and 0.57% (3 in 524 patients) in the
      cilostazol group, with a significant reduction in the cilostazol group. The rates
      of complications and pneumonia risk factors showed no difference between the two
      groups. We conclude that the administration of cilostazol to patients with
      cerebral infarction in the chronic stage does not only reduce the recurrence of
      infarction but also the incidence of pneumonia at least in Japanese patients.

PMID- 16645268
TI  - Poststroke dementia.
AB  - The association between stroke and dementia is frequent. The prevalence of
      poststroke dementia (PSD) ranges from 6 to 32%, depending on the population
      studied, the criteria used for the diagnosis of dementia, and the time interval
      between the stroke and the neuropsychological assessment. The risk of PSD is high
      immediately after stroke and remains higher than in controls in stroke patients
      nondemented 3 months after stroke. Not all cases of PSD are vascular in origin,
      with about one third of demented patients diagnosed as having Alzheimer's disease
      plus stroke. The pathophysiology of PSD is probably multifactorial, with an
      influence of vascular lesions, associated Alzheimer's lesions and white matter
      changes. The risk of dementia is higher in older patients and in patients with
      preexisting cognitive decline - no dementia, severe stroke, a history of stroke,
      white matter changes and cerebral atrophy. The influence of stroke location,
      vascular risk factors and silent infarcts remains to be determined. PSD adversely
      influences the outcome in stroke patients.

PMID- 16645269
TI  - Moyamoya-like vascular abnormality in pulmonary sarcoidosis.

PMID- 16645270
TI  - Differential susceptibility to etoposide in clones derived from a human ovarian
      cancer cell line.
AB  - OBJECTIVES: To identify parameters/factors that may contribute to the
      differential sensitivity to etoposide in two clones isolated from the human
      ovarian carcinoma SKOV-3 cell line, which does not express p53 and is resistant
      to platinum-based regimens. METHODS: Differential sensitivity of the cells to
      etoposide was monitored by microscopy to observe morphological changes, by flow
      cytometry analyses to detect cell cycle perturbations, and by
      molecular/biochemical assays to identify events involved in induction of
      apoptosis. RESULTS: Etoposide treatment (1) induced apoptosis in one clone, ES,
      but not in another clone, ER, (2) had no effect on the expression of the
      antiapoptotic proteins Bcl-2 and Bcl-X(L) in both cell clones, whereas the
      proapoptotic proteins Bak and Bax were dramatically upregulated in ES, but not ER
      cells, and (3) induced more extensive processing of procaspase-8, procaspase-9,
      and the caspase-3-targeted substrates, topoisomerase I and PARP, in ES cells.
      Ectopic overexpression of Bcl-2 in ES cells failed to inhibit etoposide-induced
      apoptosis. CONCLUSIONS: The differential susceptibility of ES and ER cells to
      etoposide-induced apoptosis is associated with differences in several events
      rather than with a specific single genetic regulator of the apoptotic machinery.
      We propose that the differential response of ovarian cancer patients to etoposide
      treatment is associated with the number of etoposide-sensitive cells in the
      tumor.

PMID- 16645271
TI  - Mid-term efficacy of beraprost, an oral prostacyclin analog, in the treatment of
      distal CTEPH: a case control study.
AB  - BACKGROUND: Prostanoids are a well-established therapy for pulmonary arterial
      hypertension (PAH), and observational studies suggest their efficacy even in
      chronic thromboembolic pulmonary hypertension (CTEPH) patients. OBJECTIVE: To
      compare the effects of 6 months of treatment with beraprost, an orally-active
      prostacyclin analog, in patients with distal CTEPH and PAH. DESIGN: Case-control
      study. POPULATION: Sixteen patients with severe pulmonary hypertension (NYHA II
      IV), eight with distal CTEPH matched with eight patients with idiopathic PAH for
      similar effort tolerance. METHODS: All patients were in stable clinical and
      hemodynamic condition for 3 months with maximal standard therapy. During the
      titration phase (4 weeks) beraprost was increased to maximal tolerated dose (mean
      daily dosage: CTEPH 275 +/- 47 microg, PAH 277 +/- 47 microg) in adjunction of
      standard therapy, patients were followed-up for 6 months. MAIN OUTCOME MEASURES:
      World Heart Organization (WHO) functional class, exercise capacity measured by
      distance walked in 6 min, and systolic pulmonary pressure (echocardiography),
      were evaluated at baseline, and at 1-, 3- and 6-month interval. RESULTS: At 6
      months WHO class decreased significantly in both groups (CTEPH from 2.7 +/- 0.6
      to 2.0 +/- 0.24, p < 0.05; PAH from 3.0 +/- 0.26 to 2.1 +/- 0.25, p < 0.05),
      similarly the 6-min walk distance increased significantly from baseline (CTEPH
      from 312 +/- 31 to 373 +/- 29 m, p < 0.003; PAH from 303 +/- 31 to 347 +/- 29, p
      < 0.0003). Systolic pulmonary artery pressure showed a trend toward lower value
      (CTEPH from 85 +/- 7 m to 81 +/- 6 mm Hg, p = NS; PAH from 89 +/- 7 to 82 +/- 5,
      p = NS). During the observation period we did not have any death. The drug was
      well-tolerated with minor side-effects. CONCLUSION: In patients with CTEPH
      beraprost had similar mid-term clinical and hemodynamic improvements than in
      patients with PAH.

PMID- 16645272
TI  - Brief informant screening test for mild cognitive impairment and early
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: Recent research has attempted combinations of instruments to
      improve screening accuracy for mild cognitive impairment (MCI) and early
      Alzheimer's disease (AD). We compared Mini-Mental State Examination (MMSE),
      Immediate and Delayed Recall (Logical Memory I and II; LM-I and LM-II,
      respectively), a single-item informant report of memory problem (IRMP), and a
      four-item Instrumental Activities of Daily Living (4IADL) scale, and combinations
      of these tests. METHOD: The tests were administered together with Clinical
      Dementia Rating (CDR) to subjects who were cognitively intact (CDR = 0, n = 88),
      and with diagnoses of MCI (CDR = 0.5, n = 37) and early AD (CDR = 1-2, n = 19).
      RESULTS: Screening accuracy (receiver operating characteristic area under curve,
      AUC) for identifying MCI or MCI-AD was lowest for MMSE (AUC 67.6% for MCI or
      77.9% for MCI-AD), and better for IRMP (79.5 or 83.2%), 4IADL (76.9 or 84.7%), LM
      I (81.2 or 87.1%) and LM-II (86.1 or 90.8%). Combining IRMP, 4IADL and LM-II was
      most accurate (AUC 91.7% for MCI or 94.5% for MCI-AD); sensitivity: 86.5 or
      89.3%; specificity: 86.4 or 88.6%. However, combining IRMP and 4IADL gave nearly
      as good accuracy (AUC 87.2 or 91.6%); sensitivity: 86.5 or 85.7%; specificity:
      79.5 or 85.2%. CONCLUSION: A brief instrument combining an IRMP and 4IADL items
      is potentially useful in screening for MCI and early AD.

PMID- 16645273
TI  - Is mortality increased in mildly cognitively impaired individuals? A systematic
      literature review.
AB  - Numerous studies have focused on the effect of mild cognitive impairment in
      elderly people. However, the impact of mild cognitive impairment on mortality has
      rarely been considered so far. This paper reviews recent work on mild cognitive
      impairment and its mortality risk. Relevant articles were identified by a
      systematic search of the literature published since 1990 using the databases
      PubMed, Web of Science and PSYNDEXplus, bibliographies of articles identified and
      of earlier reviews. Those studies were considered which predominantly included
      persons aged 65 and over and which relied on population-based samples. Thus only
      eight studies could be identified. In general, the relative risk (RR) for
      subjects with mild cognitive impairment according to different concepts in
      comparison to non-affected persons varies from 1.0 to 1.9. However, only few
      studies are available, and a comparison of the literature is problematic, due to
      variations in criteria and methodology.

PMID- 16645274
TI  - Differences in risk factors for dementia with neurodegenerative traits and for
      vascular dementia.
AB  - In 229 patients with dementia and in 144 control subjects, polymorphisms of
      apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein,
      alpha(2)-macroglobulin, interleukin (IL) 1beta, angiotensin-converting enzyme and
      of methylene tetrahydrofolate reductase genes were investigated. In plasma,
      antibodies against Chlamydia pneumoniae and lipids were determined. Dementia was
      classified as probable Alzheimer's disease (AD), probable dementia of vascular
      origin (VaD) and mixed dementia (MD). An association of the disease with ApoE and
      IL-1beta polymorphism and increased levels of LDL cholesterol were observed in AD
      and in MD but not in VaD.

PMID- 16645275
TI  - Microbleeds in Alzheimer disease are more related to cerebral amyloid angiopathy
      than cerebrovascular disease.
AB  - Cerebral amyloid angiopathy (CAA) is one of the cardinal pathological features in
      the vascular components of Alzheimer's disease (AD). CAA itself results in
      disrupted microvasculature, mainly in the cerebral cortex, eventually leading to
      a brain cortical or subcortical hemorrhage in a population of elderly people, but
      clinically overt brain hemorrhages are not so frequent in AD patients. Here we
      assessed 50 AD patients and 26 controls to detect latent brain hemorrhages with
      gradient-echo T(2)*-weighted images, a sensitive magnetic resonance imaging
      technique to detect hemosiderin components in the brain. Microbleeds, demarcated
      as low-intensity spots in T(2)*-weighted images, were detected in 16.7% of AD
      patients without cerebrovascular disease (CVD) and in 12.5% of those with CVD,
      while no microbleeding was detected in the control subjects. No significant
      difference was observed between the microbleed-positive group and the microbleed
      negative counterpart in their clinical background, such as hypertension, the use
      of antiplatelet drugs and smoking. In addition, white matter high intensities in
      the T(2)-weighted image were significantly more confluent in the microbleed
      positive AD group than its negative counterpart. In conclusion, our evaluation of
      AD brains revealed that latent microbleeds in AD patients are more frequent than
      in normal controls. Microbleeds not being related to common hemorrhagic risk
      factors, but being significantly related to white matter pathologies suggested
      that microbleeds in AD may be associated with CAA, but not with hypertension or
      CVD.

PMID- 16645276
TI  - Apolipoprotein E epsilon4 allele frequency in vascular dementia.
AB  - AIM: The aim of the study was to investigate whether possession of the epsilon4
      allelic form of the apolipoprotein E (APOE) gene increases the risk of developing
      vascular dementia (VaD). METHODS: APOE allele and genotype frequencies were
      determined by PCR in 89 patients with possible and probable VaD and compared with
      those in 97 patients with possible and probable Alzheimer's disease (AD) of
      similar age of disease onset and ethnic background, and with 766 control subjects
      drawn from the same geographical region. RESULTS: The APOE epsilon4 allele
      frequency in all 97 patients with possible and probable AD was significantly
      higher (p < 0.001) than that in control subjects. However, the APOE epsilon4
      allele frequency in all 89 patients with possible and probable VaD was also
      significantly higher (p < 0.001) than that in control subjects, but not
      significantly different from that in AD. The APOE epsilon4 allele frequency was
      similarly, and still significantly (p < 0.001), increased when only those
      patients with probable AD or probable VaD were considered. CONCLUSION: Possession
      of APOE epsilon4 allele increases the risk of VaD.

PMID- 16645278
TI  - Short- and long-term outcomes of spontaneous CSF hypovolemia.

PMID- 16645280
TI  - Dejerine-Sottas disease (progressive hypertrophic polyneuropathy).

PMID- 16645284
TI  - Is gastrin partially responsible for body weight reduction after gastric bypass?
AB  - BACKGROUND: The rationale for bariatric surgery is to reduce food intake by
      gastric restriction and/or malabsorption by intestinal bypass. Unlike ghrelin,
      gastrin is released in response to food intake. Here we studied the possible role
      of gastrin in the reduction of body weight after gastric bypass surgery. METHODS:
      Rats were divided into four experimental groups and were subjected to different
      treatments: sham operation, gastric bypass, sham operation + gastrin infusion,
      and gastric bypass + gastrin infusion. The gastric bypass was done by
      anastomosing the esophagus to the duodenal bulb without bypassing the intestine.
      Gastrin-17 was infused continuously for 2 months via subcutaneously implanted
      osmotic minipumps. Body weights were recorded; serum gastrin and ghrelin levels
      were measured, and the stomachs were analyzed morphologically. RESULTS: Gastric
      bypass resulted in reducing the body weight, stomach weight, thickness of the
      oxyntic mucosa, serum gastrin concentration, and activity of the ECL cells.
      Gastrin infusion prevented mucosal atrophy and ECL cell inactivation, and
      attenuated the body weight reduction that occurred following gastric bypass.
      Circulating ghrelin and ghrelin-producing A-like cells in stomachs that had
      undergone gastric bypass were unchanged with or without gastrin infusion and are
      thus unlikely to be responsible for the reduced body weight. CONCLUSION: We
      suggest that hypogastrinemia and impaired ECL cell function in the oxyntic mucosa
      of the stomach might be partially responsible for the reduction in body weight
      that occurs after gastric bypass.

PMID- 16645285
TI  - [Complementary medicine and the ":human factor"].

PMID- 16645286
TI  - Physicians' philosophy of care: a comparison of complementary and conventional
      medicine.
AB  - BACKGROUND: This project is part of an evaluation of complementary and
      alternative medicine (CAM) aimed at providing a scientific basis for the Swiss
      Government to include 5 CAM methods in basic health coverage: anthroposophic
      medicine, homeopathy, neural therapy, phytotherapy and Traditional Chinese
      Medicine (TCM). OBJECTIVES: The objective was to explore the philosophy of care
      (convictions and values, priorities in medical activity, motivation for CAM,
      criteria for the practice of CAM, limits of the used methods) of conventional and
      CAM general practitioners (GPs) and to determine differences between both groups.
      MATERIALS AND METHODS: This study was a cross-sectional survey of a
      representative sample of 623 GPs who provide complementary or conventional
      primary care. A mailed questionnaire with open-ended questions focusing on the
      philosophy of care was used for data collection. An appropriate methodology using
      a combination of quantitative and qualitative approaches was developed. RESULTS:
      Significant differences between both groups include philosophy of care (holistic
      versus positivistic approaches), motivation for CAM (intrinsic versus extrinsic)
      and priorities in medical activity. Both groups seem to be aware of limitations
      of the therapeutic methods used. The study reveals that conventional physicians
      are also using complementary medicine. DISCUSSION: Our study provides a wealth of
      data documenting several aspects of physicians' philosophy of care as well as
      differences and similarities between conventional and complementary care.
      Implications of the study with regard to quality of care as well as ethical and
      health policy issues should be investigated further.

PMID- 16645287
TI  - Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of
      sinusitis.
AB  - BACKGROUND: The herbal formula BNO-101 (containing Gentianae radix, Primulae
      flos, Rumicis herba, Sambuci flos and Verbenae herba; ratio 1:3:3:3:3) has been
      widely employed as a 'mucoactive' agent in Germany for 70 years for the symptoms
      of respiratory infections. This paper reviews the clinical evidence of BNO-101 in
      sinusitis. METHODS: The systematic search identified 22 studies with BNO-101. Out
      of these, 6 controlled trials on sinusitis were reassessed according to
      predefined criteria. 4 trials had almost identical designs and could be examined
      by meta-analysis. RESULTS: The database comprised approximately 900 patients,
      mostly young adult males. After 2 weeks of treatment, verum was significantly
      superior to placebo (2 RCTs, 159 vs. 160 patients, both add-on to antibacterial
      treatment). The benefit regards the patients' assessment ('cured': verum = 61.1%,
      placebo = 34.5%), reduction of drain obstruction, headache and radiological signs
      (all p < 0.05). Comparing BNO-101 to ambroxol (2 RCTs, 151 vs. 150 patients, add
      on to antibacterials in 13% of the cases) the patients' assessment after 2 weeks
      showed no difference, although it favoured BNO-101 in chronic cases ('cured' BNO
      101 = 37.1%, ambroxol = 12.5%; p < 0.05). It also favoured BNO-101 concerning
      pyorrhoea and headache (p < 0.05). No significant differences were reported in 2
      open randomised trials vs. N-acetyl-cysteine and vs. the herbal product Myrtol
      std. CONCLUSIONS: BNO-101, combined with standard antibacterial therapy,
      significantly reduces the acute symptoms and signs of sinusitis. The effects are
      of the same order of magnitude as observed with other mucoactive agents. In the
      trials investigated BNO-101 had a favourable risk/benefit ratio, with an
      incidence of adverse events similar to placebo.

PMID- 16645288
TI  - Why do parents take their children to homeopaths? -- an exploratory qualitative
      study.
AB  - BACKGROUND: There has been a threefold increase in the proportion of children
      among patients visiting homeopaths in Norway from 1985 to 1998. As no study has
      investigated the reasons for this increase, the aim of the present study was to
      explore why parents take their children to homeopaths. PARTICIPANTS AND METHODS:
      In this qualitative study, parents who had taken their child to a homeopath for
      the first time during the last 3 months were interviewed in depth using a semi
      structured interview guide. The interviews were analysed using thematic analysis
      based on techniques from grounded theory. RESULTS: 9 parents were interviewed.
      Parents consulted a medical doctor to clarify how serious their child's health
      condition was, and sought treatment from a homeopath if the symptoms were not
      dangerous. Personal recommendations or personal experience of homeopathy were
      identified as being a main factor that triggered seeking treatment specifically
      from a homeopath. The reasons they sought an alternative, or rather complement,
      to conventional medical treatment were: they did not wish to give their child
      allopathic medication; they wanted to find an alternative treatment to their
      child's currently prescribed allopathic medication; they had ceased conventional
      medication due to its side effects; to obtain treatment whilst waiting for a
      problem to be assessed; or they were not offered any treatment by their medical
      doctor. CONCLUSION: Parents took their child to a homeopath due to experiences
      with the medical encounter or treatment and due to recommendations or own
      personal experience.

PMID- 16645289
TI  - Palliative in-patient cancer treatment in an anthroposophic hospital: I.
      Treatment patterns and compliance with anthroposophic medicine.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) and most of all
      anthroposophic medicine (AM) are important features of cancer treatment in
      Switzerland. While the number of epidemiological investigations into the use of
      such therapies is increasing, there is a distinct lack of reports regarding the
      combination of conventional and CAM methods. PATIENTS AND METHODS: 144 in
      patients with advanced epithelial cancers were enrolled in a prospective quality
      of-life (QoL) study at the Lukas Klinik (LK), Arlesheim, Switzerland. Tumor
      related treatment was assessed 4 months prior to admission, during
      hospitalization and 4 months after baseline. OBJECTIVE: We aimed at giving a
      detailed account of conventional, AM and CAM treatment patterns in palliative
      care, before, during and after hospitalization, with emphasis on compliance with
      AM after discharge. RESULTS: Certain conventional treatments featured less during
      hospitalization than before but were resumed after discharge (chemotherapy,
      radiotherapy, sleeping pills, psychoactive drugs). Hormone therapy,
      corticosteroids, analgesics WHO III and antidepressants remained constant. AM
      treatment consisted of Iscador? (mistletoe), other plant- or mineral-derived
      medication, baths, massage, eurythmy, art therapy, counseling and lactovegetarian
      diet. Compliance after discharge was highest with Iscador (90%) and lowest with
      art therapy (14%). Many patients remained in the care of AM physicians. Other CAM
      and psychological methods were initially used by 39.9% of patients. After 4
      months, the use had decreased with few exceptions. CONCLUSION: During holistic
      palliative treatment in an anthroposophic hospital, certain conventional
      treatments featured less whereas others remained constant. After discharge,
      chemotherapy returned to previous levels, AM compliance remained high, the use of
      other CAM therapies low.

PMID- 16645290
TI  - Treatment in a randomized multicenter trial of acupuncture for migraine (ART
      migraine).
AB  - BACKGROUND: This paper aims to describe the characteristics of physicians and
      interventions of a large, multicenter randomized trial of acupuncture for
      migraine (ART Migraine) in order to enable acupuncturists to assess the study
      interventions. PATIENTS AND METHODS: 302 patients suffering from migraine were
      randomized to 12 sessions of semi-standardized acupuncture (6 predefined basic
      points, recommendations for optional individual choice of additional points
      given), standardized minimal acupuncture (superficial needling of at least 5 of
      10 predefined, distant non-acupuncture points) or a waiting list. 30 physicians
      trained and experienced in acupuncture from 18 centers in Germany participated in
      the trial. RESULTS: The median duration of acupuncture training of trial
      physicians was 500 h (range 140-1350). Physicians had acupuncture experience for
      10 (<1 to 25) years and had treated 200 (60 to >1000) patients with acupuncture
      in the year preceding trial participation. The 6 basic points were needled in 76
      93% of sessions. Compliance with treatment instructions varied considerably among
      centers in the acupuncture group. In contrast, compliance with the minimal
      acupuncture protocol was very good. 6 of the 30 physicians stated that they would
      have treated patients somewhat differently outside the trial, 1 completely
      differently. The trial found a significant effect of those treated with
      acupuncture compared to those on the waiting list for treatment, but minimal
      acupuncture was as effective as acupuncture. CONCLUSIONS: The treatment protocols
      for acupuncture and minimal acupuncture in ART Migraine appeared an adequate
      compromise in the specific situation and for the predefined purposes. However, a
      relevant minority of participating physicians would have treated patients
      differently outside the trial.

PMID- 16645291
TI  - Acupuncture in the treatment of painful dysfunction of the temporomandibular
      joint -- a review of the literature.
AB  - OBJECTIVE: The aim of the present study was to analyze the results of randomized
      clinical trials on the efficacy of acupuncture in the treatment of painful
      dysfunction of the temporomandibular joint. MATERIALS AND METHODS: A literature
      search of 3 electronic databases was performed, and only randomized studies
      comparing acupuncture-treated patients with either untreated or conservatively
      treated control groups were included. For this purpose, results were compared in
      narrative and tabular form. RESULTS: To date, only 8 publications representing 6
      randomized clinical trials have looked into the efficacy of acupuncture in the
      treatment of craniomandibular dysfunction. With the exception of one, all studies
      were published in Sweden, between 1985 and 1992. A more recent US study was the
      only one to apply sham acupuncture to test the efficacy of acupuncture. All
      studies share methodological shortcomings, including a lack of detailed
      descriptions of the randomization procedures, point selection, possible dropouts
      and undesirable events as well as attempts to identify a possible placebo effect
      of the acupuncture. Only 1 study investigated long-term results. Although based
      on the improvement of subjective and objective criteria, all studies consider
      acupuncture as an effective treatment for painful dysfunction of the
      temporomandibular joint, the good results achieved must be interpreted with
      caution because of the methodological shortcomings identified. CONCLUSION:
      Acupuncture appears to be a suitable complementary treatment method in the
      management of craniomandibular dysfunction. However, its significance has to be
      further evaluated in future studies.

PMID- 16645292
TI  - [Complementary treatment of pneumonia with pleural effusion].
AB  - A 43-year-old male patient was diagnosed with acute sinistral pleuropneumonia and
      a pronounced thoracic pain syndrome. Despite of his painful ailments the patient
      refused antibiotic treatment. A complementary therapy comprising physiotherapy,
      hydrotherapy, herbal therapy and vitamin C, cupping and QiGong was initiated. A
      cantharidin blister was applied topically to the left thorax in order to treat
      the pain syndrome. The multimodal CAM treatment resulted in a rapid clinical and
      x-ray resolution of pneumonia, and cantharidin treatment effectively relieved
      pain. The case and the potential of topical cantharidin in pain syndromes are
      discussed.

PMID- 16645293
TI  - A five-week exercise program can reduce falls and improve obstacle avoidance in
      the elderly.
AB  - BACKGROUND: Falls in the elderly are a major health problem. Although exercise
      programs have been shown to reduce the risk of falls, the optimal exercise
      components, as well as the working mechanisms that underlie the effectiveness of
      these programs, have not yet been established. OBJECTIVE: To test whether the
      Nijmegen Falls Prevention Program was effective in reducing falls and improving
      standing balance, balance confidence, and obstacle avoidance performance in
      community-dwelling elderly people. METHODS: A total of 113 elderly with a history
      of falls participated in this study (exercise group, n = 79; control group, n =
      28; dropouts before randomization, n = 6). Exercise sessions were held twice
      weekly for 5 weeks. Pre- and post-intervention fall monitoring and quantitative
      motor control assessments were performed. The outcome measures were the number of
      falls, standing balance and obstacle avoidance performance, and balance
      confidence scores. RESULTS: The number of falls in the exercise group decreased
      by 46% (incidence rate ratio (IRR) 0.54, 95% confidence interval (CI) 0.36-0.79)
      compared to the number of falls during the baseline period and by 46% (IRR 0.54,
      95% CI 0.34-0.86) compared to the control group. Obstacle avoidance success rates
      improved significantly more in the exercise group (on average 12%) compared to
      the control group (on average 6%). Quiet stance and weight-shifting measures did
      not show significant effects of exercise. The exercise group also had a 6%
      increase of balance confidence scores. CONCLUSION: The Nijmegen Falls Prevention
      Program was effective in reducing the incidence of falls in otherwise healthy
      elderly. There was no evidence of improved control of posture as a mechanism
      underlying this result. In contrast, an obstacle avoidance task indicated that
      subjects improved their performance. Laboratory obstacle avoidance tests may
      therefore be better instruments to evaluate future fall prevention studies than
      posturographic balance assessments.

PMID- 16645294
TI  - Age-related changes of the cutaneous microcirculation in vivo.
AB  - BACKGROUND: The architectural frameworks of the skin microcirculation are rather
      complex and change continuously with aging. But these changes are yet poorly
      documented in vivo. OBJECTIVES: Using non-invasive methods belonging to the field
      of biometrology, the study aimed to investigate quantitatively the changes of the
      cutaneous microvasculature in different anatomic sites with age. METHODS:
      Measurements were performed on crow's feet, forehead, volar forearm and dorsum of
      hand in 50 women (aged 20-74 years who consisted of 10 probands in each live
      decades). The superficial vascular plexus was scanned by videocapillaroscopy and
      assessed with the software Capilab Toolbox. The subpapillary vascular plexus was
      explored with laser Doppler flowmetry. The skin color a* was analyzed by
      chromametry. RESULTS: A marked site and age effect on the skin microcirculation
      has been demonstrated. The density of capillary loops in the eldest group
      decreased by about 40-70% compared with the youngest group whereas the vascular
      length increased by 35-156%. The capillary density in the back of the hand was 4
      times higher than in the crow's feet. The vascular length in the crow's feet was
      3 times longer than in the back of the hand. Both blood flow and skin redness
      (a*) increased also with age. CONCLUSION: Both morphology and quantification of
      the cutaneous microvasculature showed changes with site and age.
      Videocapillaroscopy associated to an image processing and laser Doppler flowmetry
      revealed different vascular layers. So the combination of both instruments offers
      an easy way to observe the architectural frameworks in vivo.

PMID- 16645295
TI  - Is hand-held dynamometry useful for the measurement of quadriceps strength in
      older people? A comparison with the gold standard Bodex dynamometry.
AB  - BACKGROUND: The lower limb muscle strength is an important determinant of
      physical function in older people. However, measurement in clinical and
      epidemiological settings has been limited because of the requirement for large
      scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD)
      has been developed to measure the quadriceps strength in a supine position.
      OBJECTIVE: The objective of this study was to assess the validity of this new
      methodology for measuring the lower limb muscle strength compared to the gold
      standard Biodex dynamometer. METHODS: The supine quadriceps strength was measured
      twice with each of the Biodex and the HHD in 20 men and women, aged 61-81 years,
      on their non-dominant leg. The agreement between the peak torques obtained by
      Biodex and HHD was analyzed. RESULTS: The mean peak Biodex and HHD results were
      83.4 +/- (SD) 28.0 Nm and 68.9 +/- 19.6 Nm, respectively. The HHD undermeasured
      the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to
      the Biodex, and this effect was most marked in the strongest participants.
      Nevertheless, there was a good correlation between the measures (r = 0.91, p <
      0.0001). Classification of individuals into tertiles of muscle strength showed
      good agreement between the two methods (Kappa = 0.69, p < 0.0001). CONCLUSIONS:
      Our findings suggest that the HHD using a supine positioning offers a feasible,
      inexpensive, and portable test of quadriceps muscle strength for use in healthy
      older people. It underestimates the absolute quadriceps strength compared to the
      Biodex particularly in stronger people, but is a useful tool for ranking muscle
      strength of older people in epidemiological studies. It may also be of value for
      quick and objective assessment of physical function in the clinical setting.

PMID- 16645296
TI  - Food habits and intake of nutrients in elderly patients with Parkinson's disease.
AB  - BACKGROUND: Weight loss is reported frequently in patients with Parkinson s
      disease also early during the disease. OBJECTIVE: To investigate food habits and
      nutrient intake in elderly Parkinson s disease patients compared with matched
      controls, as well as to compare PD patients with and without weight loss.
      METHODS: Twenty-six elderly free-living patients with PD, and 26 sex- and age
      matched healthy controls, were assessed twice with one year interval between. All
      food consumed was recorded over 3 consecutive days. Food habits were assessed
      with the Food Based Concept for Classification of Eating Episodes and intakes of
      energy and nutrients were calculated. PD symptoms, olfaction, swallowing
      function, daily activities and serum concentration of different nutrients were
      investigated. RESULTS: After 1 year, the PD patients decreased their intakes of
      daily high quality snacks from 0.5 +/- 0.7 to 0.3 +/- 0.3 (p < 0.05) and their
      prepared complete meals from 0.8 +/- 0.3 to 0.6 +/- 0.3 (p < 0.05), while their
      daily number of prepared incomplete meals increased from 0.2 +/- 0.2 to 0.3 +/-
      0.3 (p < 0.01). PD patients with weight loss increased their daily intakes of fat
      by 12 +/- 34 g and their energy intake per kg body weight increased by 21 +/- 31
      kJ (p < 0.05), respectively, and this was higher than in those without weight
      loss (p < 0.01). PD patients required more help with buying and cooking food
      compared with the controls. CONCLUSIONS: PD patients' food habits changed so that
      they consumed a lower number of prepared complete meals. PD patients with weight
      loss had a higher intake of fat and energy than those without weight loss,
      although this was obviously not sufficient to prevent weight loss. Impaired
      absorption of fat in PD should be discussed.

PMID- 16645297
TI  - Outcome of older critically ill patients: a matched cohort study.
AB  - BACKGROUND: Admission of older patients to intensive care units is a
      controversial issue. OBJECTIVE: To estimate age-associated mortality of
      critically ill patients. METHODS: A prospective matched cohort study in the
      Medical-Surgical Intensive Care Unit of a tertiary hospital was conducted. We
      included 100 consecutive patients older than 70 years admitted to the intensive
      care unit (cases) and 100 patients younger than 70 years (controls). The matching
      criterion was the severity of illness at admission to the intensive care unit as
      estimated by the simplified acute physiological score (SAPS II) without including
      age in its calculation. RESULTS: Mortality in the intensive care unit was higher,
      but not statistically significant, in the older group: 26% vs. 19% (p = 0.23).
      Patients older than 70 years had a longer duration of mechanical ventilation
      (median 7 vs. 3 days) and longer stay in the intensive care unit (median 8 vs. 5
      days). There were no differences in organ dysfunctions, except for a higher
      incidence of respiratory failure in the older group (p < 0.001). The use of
      invasive procedures was similar in both groups. There were more orders for the
      withholding/withdrawal of treatment in patients older than 70 years (9 vs. 3%, p
      = 0.07). CONCLUSION: In our study, age was not related with a significant higher
      mortality. In the older patients included in our study the survival was greater
      than 70% with a similar resource utilization except for a longer stay in the
      intensive care unit.

PMID- 16645298
TI  - Footwear characteristics and risk of indoor and outdoor falls in older people.
AB  - BACKGROUND: Footwear characteristics have been shown to influence balance in
      older people; however, the relationship between footwear and falls is unclear.
      OBJECTIVE: To determine the relationships between footwear characteristics and
      the risk of indoor and outdoor falls in older people. METHODS: Footwear
      characteristics (shoe type, heel height, heel counter height, heel width,
      critical tipping angle, method of fixation, heel counter stiffness, sole rigidity
      and flexion point, tread pattern and sole hardness) were assessed in 176 people
      (56 men and 120 women) aged 62-96 (mean age 80.1, SD 6.4) residing in a
      retirement village. Falls were recorded over a 12-month follow-up period and
      comparisons made between fallers and non-fallers. RESULTS: 50 participants (29%)
      fell indoors and 36 (21%) fell outdoors. After controlling for age, gender,
      demographic characteristics, medication use, physiological falls risk factors and
      foot problems, those who fell indoors were more likely to go barefoot or wear
      socks inside the home (OR = 13.74; 95% CI 3.88-48.61, p < 0.01). However, there
      were no significant differences in indoor or outdoor footwear characteristics
      between fallers and non-fallers. Five indoor fallers (10%) and three outdoor
      fallers (8%) stated that their shoes contributed to their fall. CONCLUSION:
      Footwear characteristics were not significantly associated with falls either
      inside or outside the home. Risk of falling indoors was associated with going
      barefoot or wearing socks. Older people at risk of falling should therefore be
      advised to wear shoes indoors where possible.

PMID- 16645299
TI  - Social contacts and their relationship to loneliness among aged people - a
      population-based study.
AB  - BACKGROUND: Emotional loneliness and social isolation are major problems in old
      age. These concepts are interrelated and often used interchangeably, but few
      studies have investigated them simultaneously thus trying to clarify their
      relationship. OBJECTIVES: To describe the prevalence of loneliness among aged
      Finns and to study the relationship of loneliness with the frequency of social
      contacts, with older people's expectations and satisfaction of their human
      relationships. Especially, we wanted to clarify whether emotional loneliness is a
      separate concept from social isolation. METHODS: The data were collected with a
      postal questionnaire. Background information, feelings of loneliness, number of
      friends, frequency of contacts with children, grandchildren and friends, the
      expectations of frequency of contacts as well as satisfaction of the contacts
      were inquired. The questionnaire was sent to a random sample of 6,786 aged people
      (>74 years) in various urban and rural areas in Finland. We report here the
      results of community-dwelling respondents (n = 4,113). MAIN RESULTS: More than
      one third of the respondents (39.4%) suffered from loneliness. Feeling of
      loneliness was not associated with the frequency of contacts with children and
      friends but rather with expectations and satisfaction of these contacts. The most
      powerful predictors of loneliness were living alone, depression, experienced poor
      understanding by the nearest, and unfulfilled expectations of contacts with
      friends. CONCLUSION: Our findings support the view that emotional loneliness is a
      separate concept from social isolation. This has implications for practice.
      Interventions aiming at relieving loneliness should be focused on enabling an
      individual to reflect her own expectations and inner feelings of loneliness.

PMID- 16645300
TI  - An instrument to measure engagement in life: factor analysis and associations
      with sociodemographic, health and cognition measures.
AB  - BACKGROUND: It has been proposed that active engagement with life may protect
      against cognitive decline. However, existing instruments for measuring life
      engagement have covered limited domains. OBJECTIVE: To present a new instrument
      to measure engagement with life; the RIASEC Activities List draws on activities
      categorised according to interest categories previously developed by Holland:
      Realistic, Investigative, Artistic, Social, Enterprising and Conventional
      (RIASEC). METHODS: Participants in a longitudinal, community-based survey were
      drawn from 3 age groups: 2,404 participants aged 20-24; 2,530 aged 40-44, and
      2,551 aged 60-64 years. They provided information on which of 54 selected
      activities they had performed in the 6 months prior to their survey interview.
      Other information obtained from participants included measures of
      sociodemographic characteristics, personality attributes and mental and physical
      health. Two measures of cognition were also examined. Analyses were conducted
      separately for men and women in each of the 3 age groups. RESULTS: Confirmatory
      factor analyses identified six scales of activity types corresponding to
      Holland's six interest categories. The number of activities of any type
      undertaken in the past 6 months was significantly associated with cognitive
      measures, better physical health, and better mental health although these
      findings varied for men and women across the 3 age groups. Further, for both men
      and women in all age groups, performing activities of any type was associated
      with having higher extraversion and mastery scores, and lower levels of
      neuroticism. Associations were also found between performing specific types of
      activities and cognitive measures. CONCLUSIONS: This instrument has the potential
      to identify more clearly types of activities that may offer cognitive benefits
      and warrants further testing in longitudinal studies.

PMID- 16645301
TI  - Complete cytoreduction combined with early postoperative intraperitoneal
      chemotherapy for ovarian carcinosarcoma. Report of two cases.
AB  - BACKGROUND/AIMS: The purpose of the study is to report two long-term survivors
      with ovarian carcinosarcomas, which are rare intrapelvic malignancies with
      unfavorable prognosis. METHODS: Two middle-aged women with palpable abdominal
      tumors underwent complete cytoreductive surgery and no macroscopic tumor was left
      behind. Early postoperative intraperitoneal chemotherapy with doxorubicin was
      used as an adjuvant treatment. RESULTS: The patients are disease-free 2 and 3
      years, respectively after the initial therapy. CONCLUSION: Complete cytoreduction
      combined with early postoperative intraperitoneal chemotherapy seems to be an
      effective treatment for ovarian carcinosarcoma with peritoneal spread. Further
      studies are required to define the value of intraperitoneal chemotherapy in
      ovarian carcinosarcoma.

PMID- 16645302
TI  - NAD dependent 11beta-hydroxysteroid dehydrogenase activity in human endometrium
      and endometrial tumors.
AB  - BACKGROUND: The isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD)
      types 1 and 2, regulated by ovarian steroids, catalyze the interconversion of
      glucocorticoids and their 11-keto metabolites. The role of these enzymes in
      malignancies of human endometrium is unknown. We compare NAD dependent 11beta-HSD
      (type 2) activity levels among normal human endometrium and endometrial
      carcinomas of differing grades and histologies. METHODS: NAD dependent 11beta-HSD
      activity was determined in endometrial tissue obtained from patients undergoing
      hysterectomy for benign or malignant disease (endometroid, serous and
      carcinosarcomas). Student's t test was utilized with p < 0.05 considered
      significant. Data are presented as mean +/- SD. RESULTS: NAD dependent 11beta-HSD
      activity was present in all endometrial samples. The activities were 0.61+/- 0.27
      in normal (n = 9), 0.43 +/- 0.29 in endometrioid endometrial carcinoma (n = 14),
      0.50 +/- 0.26 in uterine serous carcinoma (n = 6) and 0.25 +/- 0.37 in
      carcinosarcomas (n = 9). NAD dependent 11beta-HSD activity was lower in the
      carcinosarcoma group as compared to normal endometrial tissue (p = 0.03).
      CONCLUSIONS: NAD dependent type 2 11beta-HSD activity was demonstrated in all
      normal and endometrial tumors. Enzyme activity in endometroid and uterine serious
      carcinoma tumors was similar to enzyme activity in normal endometrium. In
      contrast, carcinosarcomas show significantly lower enzyme activity compared to
      normal tissue.

PMID- 16645303
TI  - Does the hyperfiltration of minoxidil result in increased proteinuria and loss of
      renoprotection conferred by angiotensin inhibition?
AB  - The objective of the present study was to retrospectively examine whether the
      addition of minoxidil to patients who were already treated with maximum doses of
      angiotensin-converting enzyme inhibitors and angiotensin receptor blockers but
      who had not achieved target blood pressures, has any detrimental effect on
      proteinuria or renal function or whether its effect on blood pressure prove
      salutary. The clinical records of the patients seen at the Hypertension,
      Nephrology, Dialysis and Transplantation Clinic from June 1982 through May 2005
      were reviewed to identify 54 patients (78% men, 82% African-American) who had
      taken minoxidil (with and without angiotensin inhibition and blockade) and who
      had documented 24-hour urines for creatinine clearance and quantification of
      proteinuria before the initiation of minoxidil and after the blood pressure had
      stabilized on its final dose. The study was done at the Hypertension, Nephrology,
      Dialysis and Transplantation Clinic, the regional referral center for renal
      problems in eastern Alabama, USA. Minoxidil, whether alone or in combination with
      maximum doses of ACEIs and ARBs, was very successful in reduction of mean
      arterial pressure, but there was a tendency towards an increase in proteinuria.
      When minoxidil was given alone, patients demonstrated a trend towards reduction
      of proteinuria associated with blood pressure reduction; however, when minoxidil
      was added after the maximal doses of ACEIs and ARBs had been reached there was a
      significant increase in proteinuria (p = 0.017) on paired comparison in the same
      patients whose proteinuria had already demonstrated a significant decrease (p =
      0.02) on the ACEI and ARB alone despite further significant reduction of blood
      pressure with the minoxidil (p = 0.003). Renal function deterioration to end
      stage renal disease correlated with increase in proteinuria (p = 0.03). We
      conclude that minoxidil was very effective in lowering systemic blood pressure
      but when given to patients already on maximum doses of ACEI and ARBs, there was
      an increase in proteinuria which could be interpreted as a detrimental effect
      having in mind that the blood pressure was significantly lowered.

PMID- 16645304
TI  - Mycophenolate mofetil ameliorates accelerated progressive nephropathy in rat.
AB  - BACKGROUND: Renal ischemia and hypertension have been suggested to be involved in
      the progression of renal diseases. Recently, we developed a model of accelerated
      major histocompatibility complex-independent renal injury, where high-renin
      hypertension aggravates functional and morphological changes induced by
      ischemia/reperfusion (I/R). In this model, we evaluated the effect of
      immunosuppressant mycophenolate mofetil (MMF) to test its capability to slow the
      progression of accelerated nephropathy. METHODS: 34 anesthetized
      uninephrectomized hypertensive transgenic (mREN2)27 rats (TGR) received a clamp
      on the renal pedicle for 45 min. Animals were treated with MMF 10 mg/kg/day (n =
      10), 20 mg/kg/day (n = 10) or placebo (n = 10) orally via gavage for 12 weeks.
      Four animals were sham operated and not treated. Proteinuria and blood pressure
      were evaluated throughout the experiment. At the end of the experiment, kidney
      function was evaluated and kidneys harvested for morphological analysis and
      immunohistochemistry (CD4+, CD8+ lymphocytes and specific rat monocyte/macrophage
      marker ED-1+ cells). RESULTS: At week 12, both MMF-treated groups had lower
      proteinuria as compared to the placebo group (MMF 10: 22.4 +/- 9.8, MMF 20: 20.9
      +/- 5.6 vs. 126.7 +/- 35.8; p < 0.01; sham 28.1 +/- 1.4 mg/day) and reduced
      glomerulosclerosis (MMF 10: 11.4 +/- 7.8, MMF 20: 5.2 +/- 2.7 vs. 20.9 +/- 10.9;
      p < 0.05; sham 15.7 +/- 9.2%). There were no differences in systolic blood
      pressure among groups. MMF-treated rats had lower CD4+ (MMF 10: 61.2 +/- 46.4,
      MMF 20: 29.3 +/- 18.2 vs. 125.3 +/- 42.8; p < 0.01, sham 84.9 +/- 6.1 cells/field
      of view) and CD8+ (MMF 10: 13.7 +/- 10.2, MMF 20: 10.0 +/- 8.1 vs. 37.8 +/- 14.3;
      p < 0.01; sham: 31.8 +/- 7.6 cells/field of view) lymphocytes infiltration and ED
      1 macrophages infiltration (MMF 10: 5.5 +/- 6.4, MMF 20: 2.5 +/- 2.8 vs. 16.7 +/-
      4.1; p < 0.01; sham 12.2 +/- 4.6 cells/field of view) than placebo-treated rats.
      CONCLUSION: Our results thus support the hypothesis about the key role of immune
      mechanisms in progression of chronic nephropathies.

PMID- 16645305
TI  - Structure of functional modules from energy-transducing complexes in prokaryotes:
      examples for molecular machines.

PMID- 16645306
TI  - Biochemical and structural analysis of the Bacillus subtilis ABC transporter OpuA
      and its isolated subunits.
AB  - Adaptation of microorganisms to changing osmotic conditions is a prerequisite for
      survival and cellular vitality for most microorganisms. In the Gram-positive soil
      bacterium Bacillus subtilis, five transport systems catalyze the uptake of
      compatible solutes across the plasma membrane that allow the growth of B.
      subtilis over a wide range of osmotic conditions. Focus of this review is the
      osmoprotectant uptake A (OpuA) transporter, a member of the family of substrate
      binding protein (SBP)-dependent ATP-binding cassette (ABC) transporters that
      mediates the uptake of the compatible solutes glycine betaine and proline
      betaine. OpuA is composed of three subunits: a nucleotide-binding domain (OpuAA)
      located in the cytosol, a transmembrane domain (OpuAB), and a SBP (OpuAC), which
      binds glycine betaine and proline betaine with high specificity and targets it to
      OpuAB for ATP-dependent translocation across the plasma membrane. After a brief
      introduction in the field of bacterial osmoadaptation, we will summarize our
      recent findings about the biochemical and structural analysis of the components
      of the OpuA systems. Our studies covered both the isolated subunits of the OpuA
      transporter and initial investigations of the whole transporter in vitro.

PMID- 16645307
TI  - Energy-converting [NiFe] hydrogenases: more than just H2 activation.
AB  - The well-characterized [NiFe] hydrogenases have a key function in the H2
      metabolism of various microorganisms. A subfamily of the [NiFe] hydrogenases with
      unique properties has recently been identified. The six conserved subunits that
      build the core of these membrane-bound hydrogenases share sequence similarity
      with subunits that form the catalytic core of energy-conserving NADH:quinone
      oxidoreductases (complex I). The physiological role of some of these hydrogenases
      is to catalyze the reduction of H+ with electrons derived from reduced
      ferredoxins or polyferredoxins. This exergonic reaction is coupled to energy
      conservation by means of electron-transport phosphorylation. Other members of
      this hydrogenase subfamily mainly function in providing the cell with reduced
      ferredoxin using H2 as electron donor in a reaction driven by reverse electron
      transport. These hydrogenases have therefore been designated as energy-converting
      [NiFe] hydrogenases.

PMID- 16645308
TI  - Sodium ion pumps and hydrogen production in glutamate fermenting anaerobic
      bacteria.
AB  - Anaerobic bacteria ferment glutamate via two different pathways to ammonia,
      carbon dioxide, acetate, butyrate and molecular hydrogen. The coenzyme B12
      dependent pathway in Clostridium tetanomorphum via 3-methylaspartate involves
      pyruvate:ferredoxin oxidoreductase and a novel enzyme, a membrane-bound
      NADH:ferredoxin oxidoreductase. The flavin- and iron-sulfur-containing enzyme
      probably uses the energy difference between reduced ferredoxin and NADH to
      generate an electrochemical Na+ gradient, which drives transport processes. The
      other pathway via 2-hydroxyglutarate in Acidaminococcus fermentans and
      Fusobacterium nucleatum involves glutaconyl-CoA decarboxylase, which uses the
      free energy of decarboxylation to generate also an electrochemical Na+ gradient.
      In the latter two organisms, similar membrane-bound NADH:ferredoxin
      oxidoreductases have been characterized. We propose that in the hydroxyglutarate
      pathway these oxidoreductases work in the reverse direction, whereby the
      reduction of ferredoxin by NADH is driven by the Na+ gradient. The reduced
      ferredoxin is required for hydrogen production and the activation of radical
      enzymes. Further examples show that reduced ferredoxin is an agent, whose
      reducing energy is about 1 ATP 'richer' than that of NADH.

PMID- 16645309
TI  - Prokaryotic Kdp-ATPase: recent insights into the structure and function of KdpB.
AB  - P-type ATPases are amongst the most abundant enzymes that are responsible for
      active transport of ions across biological membranes. Within the last 5 years a
      detailed picture of the structure and function of these transport ATPases has
      emerged. Here, we report on the recent progress in elucidating the molecular
      mechanism of a unique, prokaryotic member of P-type ATPases, the Kdp-ATPase. The
      review focuses on the catalytic parts of the central subunit, KdpB. The structure
      of the nucleotide-binding domain was solved by NMR spectroscopy at high
      resolution and a model of the nucleotide-binding mode was presented. The
      nucleotide turned out to be 'clipped' into the binding pocket by a pi-pi
      interaction to F377 on one side and a cation-pi interaction to K395 on the other.
      The 395KGXXD/E motif and thus the nucleotide-binding mode seems to be conserved
      in all P-type ATPases, except the heavy metal-transporting (class IB) ATPases.
      Hence, it can be concluded that KdpB is currently misgrouped as class IA.
      Mutational studies on two highly conserved residues (D583 and K586) in the
      transmembrane helix 5 of KdpB revealed that they are indispensable in coupling
      ATP hydrolysis to ion translocation. Based on these results, two possible
      pathways for the reaction cycle are discussed.

PMID- 16645310
TI  - Dearomatizing benzene ring reductases.
AB  - The high resonance energy of the benzene ring is responsible for the relative
      resistance of aromatic compounds to biodegradation. Nevertheless, bacteria from
      nearly all physiological groups have been isolated which utilize aromatic growth
      substrates as the sole source of cell carbon and energy. The enzymatic
      dearomatization of the benzene nucleus by microorganisms is accomplished in two
      different manners. In aerobic bacteria the aromatic ring is dearomatized by
      oxidation, catalyzed by oxygenases. In contrast, anaerobic bacteria attack the
      aromatic ring by reductive steps. Key intermediates in the anaerobic aromatic
      metabolism are benzoyl-CoA and compounds with at least two meta-positioned
      hydroxyl groups (resorcinol, phloroglucinol and hydroxyhydroquinone). In
      facultative anaerobes, the reductive dearomatization of the key intermediate
      benzoyl-CoA requires a stoichiometric coupling to ATP hydrolysis, whereas
      reduction of the other intermediates is readily achieved with suitable electron
      donors. Obligately anaerobic bacteria appear to use a totally different
      enzymology for the reductive dearomatization of benzoyl-CoA including
      selenocysteine- and molybdenum- containing enzymes.

PMID- 16645311
TI  - Structure and function of the betaine uptake system BetP of Corynebacterium
      glutamicum: strategies to sense osmotic and chill stress.
AB  - The soil bacterium Corynebacterium glutamicum has to cope with frequent
      fluctuations of the external osmolarity and temperature. The consequences of
      hyperosmotic and chill stress seem to differ, either causing dehydration of the
      cytoplasm or leading to impairment of cellular functions due to low temperature.
      Nevertheless, a particular type of regulatory response, namely the accumulation
      of so-called compatible solutes, is induced under both conditions. Compatible
      solutes are known to stabilize the native conformation of enzymes, which may be
      affected by osmotic and chill stress. BetP is a high-affinity uptake carrier for
      the compatible solute glycine betaine in C. glutamicum. BetP includes, besides
      its catalytic function, the ability to sense hyperosmotic conditions and chill
      stress. As a consequence, the carrier is activated in dependence of the extent of
      these types of stress. The signal input related to these changes of the
      environmental conditions is based on at least two different mechanisms. In case
      of hyperosmotic stress, BetP responds to the internal potassium concentration as
      a measure for hypertonicity, whereas chill stress is detected by an independent
      signal, most probably changes of the physical state of the membrane.

PMID- 16645312
TI  - Biogenesis of the bacterial respiratory CuA, Cu-S enzyme nitrous oxide reductase.
AB  - Nitrous oxide reductase (NosZ, EC 1.7.99.6) is the terminal oxidoreductase of a
      respiratory electron transfer chain that transforms nitrous oxide to dinitrogen.
      The enzyme carries six Cu atoms. Two are arranged in the mixed-valent binuclear
      CuA site, and four make up the mu4-sulfide-bridged Cu cluster, CuZ. The
      biogenesis of a catalytically active NosZ requires auxiliary functions for metal
      center assembly in the periplasm. Both Tat and Sec pathways share the task to
      transport the various Nos proteins to their functional sites. Biogenesis of NosZ
      requires an ABC transporter complex and the periplasmic Cu chaperone NosL.
      Sustaining whole-cell NosZ function depends on the periplasmic, FAD-containing
      protein NosX, and the membrane-bound iron-sulfur flavoprotein NosR. Most
      components with a biogenetic function are now amenable to structural studies.

PMID- 16645313
TI  - Bioenergetics of archaea: ATP synthesis under harsh environmental conditions.
AB  - Archaea are a heterogeneous group of microorganisms that often thrive under harsh
      environmental conditions such as high temperatures, extreme pHs and high
      salinity. As other living cells, they use chemiosmotic mechanisms along with
      substrate level phosphorylation to conserve energy in form of ATP. Because some
      archaea are rooted close to the origin in the tree of life, these unusual
      mechanisms are considered to have developed very early in the history of life
      and, therefore, may represent first energy-conserving mechanisms. A key component
      in cellular bioenergetics is the ATP synthase. The enzyme from archaea represents
      a new class of ATPases, the A1A0 ATP synthases. They are composed of two domains
      that function as a pair of rotary motors connected by a central and peripheral
      stalk(s). The structure of the chemically-driven motor (A1) was solved by small
      angle X-ray scattering in solution, and the structure of the first A1A0 ATP
      synthases was obtained recently by single particle analyses. These studies
      revealed novel structural features such as a second peripheral stalk and a collar
      like structure. In addition, the membrane-embedded electrically-driven motor (A0)
      is very different in archaea with sometimes novel, exceptional subunit
      composition and coupling stoichiometries that may reflect the differences in
      energy-conserving mechanisms as well as adaptation to temperatures at or above
      100 degrees C.

PMID- 16645314
TI  - [NiFe]-hydrogenases of Ralstonia eutropha H16: modular enzymes for oxygen
      tolerant biological hydrogen oxidation.
AB  - Recent research on hydrogenases has been notably motivated by a desire to utilize
      these remarkable hydrogen oxidation catalysts in biotechnological applications.
      Progress in the development of such applications is substantially hindered by the
      oxygen sensitivity of the majority of hydrogenases. This problem tends to inspire
      the study of organisms such as Ralstonia eutropha H16 that produce oxygen
      tolerant [NiFe]-hydrogenases. R. eutropha H16 serves as an excellent model system
      in that it produces three distinct [NiFe]-hydrogenases that each serve unique
      physiological roles: a membrane-bound hydrogenase (MBH) coupled to the
      respiratory chain, a cytoplasmic, soluble hydrogenase (SH) able to generate
      reducing equivalents by reducing NAD+ at the expense of hydrogen, and a
      regulatory hydrogenase (RH) which acts in a signal transduction cascade to
      control hydrogenase gene transcription. This review will present recent results
      regarding the biosynthesis, regulation, structure, activity, and spectroscopy of
      these enzymes. This information will be discussed in light of the question how do
      organisms adapt the prototypical [NiFe]-hydrogenase system to function in the
      presence of oxygen.

PMID- 16645315
TI  - Structure determination of secondary transport proteins by electron
      crystallography: two-dimensional crystallization of the betaine uptake system
      BetP.
AB  - Structure determination at high resolution is still a challenge for membrane
      proteins in general, but in particular for secondary transporters due to their
      highly dynamic nature. X-ray structures of ten secondary transporters have
      recently been determined, but a thorough understanding of transport mechanisms
      necessitates structures at different functional states. Electron cryo-microscopy
      of two-dimensional (2D) crystals offers an alternative to obtain structural
      information at intermediate resolution. Electron crystallography is a
      sophisticated way to study proteins in a natural membrane environment and to
      track conformational changes in situ. Furthermore, basic interactions between
      protein and lipids can be investigated. Projection and 3-dimensional maps of six
      secondary transporters from different families have been determined by electron
      crystallography of 2D crystals at a resolution of 8 A and better. In this review,
      we give an overview about the principles of 2D crystallization, in particular of
      secondary transporters, and summarize the important steps successfully applied to
      establish and improve the 2D crystallization of the high-affinity glycine betaine
      uptake system from Corynebacterium glutamicum, BetP.

PMID- 16645316
TI  - A possible role for iron-sulfur cluster N2 in proton translocation by the NADH:
      ubiquinone oxidoreductase (complex I).
AB  - The proton-pumping NADH:ubiquinone oxidoreductase, the respiratory complex I,
      couples the transfer of electrons from NADH to ubiquinone with the translocation
      of protons across the membrane. The enzyme mechanism is still unknown due to the
      lack of a high-resolution structure and its complicated composition. The complex
      from Escherichia coli is made up of 13 subunits called NuoA through NuoN and
      contains one FMN and nine iron-sulfur (Fe/S) clusters as redox groups. The pH
      dependence of the midpoint redox potential of the Fe/S cluster named N2 and its
      spin-spin interaction with ubiquinone radicals made it an ideal candidate for a
      key component in redox-driven proton translocation. During the past years we have
      assigned the subunit localization of cluster N2 to subunit NuoB by site-directed
      mutagenesis and predicted its ligation by molecular simulation. Redox-induced FT
      IR spectroscopy has shown that its redox reaction is accompanied by the
      protonation and deprotonation of individual amino acid residues. These residues
      have been identified by site-directed mutagenesis. The enzyme catalytic activity
      depends on the presence of cluster N2 and is coupled with major conformational
      changes. From these data a model for redox-induced conformation-driven proton
      translocation has been derived.

PMID- 16645317
TI  - Key bacterial multi-centered metal enzymes involved in nitrate and sulfate
      respiration.
AB  - Many essential life processes, such as photosynthesis, respiration, nitrogen
      fixation, depend on transition metal ions and their ability to catalyze multi
      electron redox and hydrolytic transformations. Here we review some recent
      structural studies on three multi-site metal enzymes involved in respiratory
      processes which represent important branches within the global cycles of nitrogen
      and sulfur: (i) the multi-heme enzyme cytochrome c nitrite reductase, (ii) the
      FAD, FeS-enzyme adenosine-5'-phosphosulfate reductase, and (iii) the siroheme,
      FeS-enzyme sulfite reductase. Structural information comes from X-ray
      crystallography and spectroscopical techniques, in special cases catalytically
      competent intermediates could be trapped and characterized by X-ray
      crystallography.

PMID- 16645318
TI  - Brain natriuretic peptide and N-terminal proBNP in chronic haemodialysis
      patients.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are
      released into circulation as a result of congestive heart failure (HF). As HF and
      water overload are frequent complications in haemodialysis (HD) patients, we
      decided to study the levels of BNP and NT-proBNP and their changes during HD.
      METHODS: BNP and NT-proBNP levels were determined in 94 HD patients before and
      after a regular 4-h HD. We followed changes in these peptides during HD depending
      on age, sex, HF (NYHA classification and left ventricular ejection fraction
      [LVEF]), duration on HD, presence of hypertension, coronary artery disease, type
      of membrane used for HD [low-flux (LFx) or high-flux (HFx)] and body mass change
      during HD. Furthermore, patients basic medication and creatinine levels and
      presence of diabetes mellitus were monitored. RESULTS: Respectively,94% and 100%
      of the patients had pre-dialysis concentrations of BNP and NT-proBNP above the
      cut-off values for HF. The marker levels correlated significantly both before and
      after HD (r = 0.903 and 0.888, respectively, p < 0.001). BNP levels significantly
      decreased (p < 0.0001), whereas NT-proBNP significantly increased (p < 0.0001)
      during HD on LFx membranes. HD on HFx membranes caused greater decrease of BNP
      (compared to LFx membranes, p < 0.001), but also a decrease of NT-proBNP (p <
      0.001).We did not find any significant differences in marker levels for HF and
      non-HF patients (NYHA classification). However, both peptides reached higher
      levels in the group with LVEF < or = 50% (p < 0.001 for both peptides). Body mass
      change during HD negatively correlated only with the change of NT-proBNP (r = 
      0.27, p < 0.05). In the multiple regression model, the change of both peptides
      during HD was significantly influenced by membrane type (p = 0.003 for BNP and p
      = 0.001 for NT-proBNP). NT-proBNP change during HD was further significantly
      influenced by LVEF (p = 0.012), sex (p = 0.002) and duration on HD (p = 0.006).
      CONCLUSIONS: Both BNP and NT-proBNP levels were significantly increased in HD
      patients prior to dialysis. The change in concentrations of both peptides during
      HD is influenced by membrane type. HD probably triggers increased production of
      both peptides and this increase is emphasized by impaired LVEF. This fact can be
      clinically observed only on NT-proBNP levels, because BNP levels are biased by
      significant removal of this protein during HD.

PMID- 16645319
TI  - Barriers to autopsy: Creutzfeldt-Jakob disease in New York state.
AB  - Surveillance of Creutzfeldt-Jakob disease (CJD) monitors trends and ensures
      timely identification of variant CJD and other emergent prion diseases. Brain
      tissue is needed to definitively diagnose these diseases. A survey of
      neurologists and pathologists in New York State was conducted to understand
      neurologists' and pathologists' views on autopsy and CJD. Neurologists reported
      using autopsy rarely or never. Over half of the pathologists worked in facilities
      that did not perform autopsies when CJD was suspected. Barriers to autopsy
      included family reluctance, infection control concerns, and local facilities
      unable to perform brain autopsy. More accurate, complete recognition of CJD and
      variant forms depends on physician awareness of the manifestations of CJD and its
      diagnosis, access to pathologists and facilities willing and able to perform
      brain biopsies and autopsies, and family acceptance of such procedures.

PMID- 16645320
TI  - Trends in risk of stroke in patients with a hospital diagnosis of nonvalvular
      atrial fibrillation: National Cohort Study in Denmark, 1980-2002.
AB  - AIM: We examined trends in incidence of stroke of any nature (ischemic and/or
      hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial
      fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions
      of comorbidity. METHODS: We identified all individuals, aged 40-89 years, with an
      incident hospital diagnosis of atrial fibrillation or flutter and no history of
      stroke or heart valve disease in the Danish National Registry of Patients, and
      subjects were followed in the Danish National Registry of Patients for occurrence
      of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic)
      and in the Danish Civil Registration System (emigration and vital status). We
      used multivariate Cox proportional hazard regression analysis to estimate trends
      in incidence of stroke. RESULTS: Nonvalvular atrial fibrillation or flutter was
      diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up
      15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke
      in the last 3-year period compared to the first 5-year period, adjusted for 10
      year age group, conditions of comorbidity, and general stroke trend in the Danish
      population were 0.78 (95% CI 0.70-0.86) in men, and 0.80 (95% CI 0.72-0.88) in
      women. The reduction in risk of stroke by calendar year was most prominent in
      patients aged 40-74 years. CONCLUSION: We observed a modest decrease in risk of
      stroke in subject with atrial fibrillation in Denmark during calendar years 1980
      2002. However, we could not control for any changes in diagnostic performance,
      admission practice, and medical management of patients with atrial fibrillation.

PMID- 16645321
TI  - Seasonal variation in stroke and stroke-associated mortality in patients with a
      hospital diagnosis of nonvalvular atrial fibrillation or flutter. A population
      based study in Denmark.
AB  - AIM: There are few data on seasonal variation in stroke and seasonal variation in
      mortality after stroke in patients with atrial fibrillation. We examined the
      seasonal pattern in stroke occurrence and the effect of the season on mortality
      after stroke in patients with a history of nonvalvular atrial fibrillation.
      METHODS: We identified all individuals, aged 40-89 years, with an incident
      diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980-2002
      period and no history of heart valve disease and a previous or concomitant
      diagnosis of atrial fibrillation or flutter in the Danish National Registry of
      Patients. Subjects were followed in the Danish Civil Registration System for
      emigration and vital status. We used periodic regression models to estimate the
      peak-trough ratio stratified by sex, age and comorbid medical conditions.
      Seasonal effect on mortality after stroke was analyzed in a Cox proportional
      hazards model. RESULTS: The relative incidence of stroke estimated as the ratio
      of the incidence in the month of the peak (January) to the incidence in the month
      of the trough (July) was 1.11 (95% confidence interval: 1.07-1.15). The relative
      incidence of stroke was similar for men and women, did not differ by age
      (stratified by age 75 years) and was essentially similar for comorbid conditions
      considered. There was no seasonal effect on mortality after stroke. CONCLUSIONS:
      The occurrence of stroke in patients with atrial fibrillation is modestly higher
      during the winter. Stroke-associated mortality does not vary by season.

PMID- 16645322
TI  - Effects of indoxylsulfate on the in vitro hepatic metabolism of various compounds
      using human liver microsomes and hepatocytes.
AB  - BACKGROUND: Alterations of hepatic drug metabolism in patients with renal failure
      are poorly understood. In this study, the effects of uremic substances that can
      be removed by hemodialysis on in vitrohepatic drug metabolism were studied using
      human liver microsomes and hepatocytes. METHODS: The metabolism of various
      compounds that undergo oxidation and glucuronidation in the liver was studied
      using human liver microsomes and hepatocytes in the presence of 11 uremic
      substances removable by hemodialysis. RESULTS: The formation of resorufin from
      ethoxyresorufin was inhibited by 3-indoxylsulfate and 3-indoleacetic acid. The
      formation of 6beta-hydroxytestosterone from testosterone was inhibited only by 3
      indoxylsulfate. These uremic substances reduced the maximum metabolic rate but
      not the affinity, suggesting that the inhibitory mechanism was noncompetitive.
      The inhibition of formation of resorufin and 6beta-hydroxytestosterone by 3
      indoxylsulfate was also observed in human hepatocytes. The elimination of
      nicardipine in liver microsomes was decreased significantly in the presence of 3
      indoxylsulfate and 3-indoleacetic acid. CONCLUSION: The hepatic metabolism of
      certain drugs may be inhibited directly by uremic substances such as 3
      indoxylsulfate that accumulate in the plasma in patients with chronic renal
      failure.

PMID- 16645323
TI  - Multicenter phase II study of gemcitabine and oxaliplatin (GEMOX) as second-line
      chemotherapy in colorectal cancer patients pretreated with 5-fluorouracil plus
      irinotecan.
AB  - PURPOSE: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin
      (GEMOX) combination as second-line chemotherapy for patients with advanced
      colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5
      FU)/leucovorin (LV) regimen. PATIENTS AND METHODS: Patients with documented
      disease progression during or after first-line treatment with CPT-11 and 5-FU/LV
      were enrolled. Gemcitabine (1,000 mg/m(2) days 1 and 8) and oxaliplatin (100
      mg/m(2) day 1) were administered every 3 weeks. RESULTS: Partial responses were
      observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis;
      overall response rate: 17.7%; 95% confidence interval 4.8-30.5%). Eight (23.5%)
      patients experienced disease stabilization and 20 (59%) disease progression
      (tumor growth control rate = 41.2%). The median duration of response was 5.5
      months, and the median time to tumor progression 2.7 months. The median overall
      survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and
      thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other
      severe non-hematologic toxicities were rare. CONCLUSION: The interesting tumor
      growth control rate and the favorable toxicity profile of the GEMOX regimen in
      pretreated patients with advanced CRC strongly suggest that this regimen may
      provide an alternative therapeutic option for this group of patients.

PMID- 16645324
TI  - Pretreatment serum levels of cytokines and cytokine receptors in patients with
      non-small cell lung cancer, and correlations with clinicopathological features
      and prognosis. M-CSF - an independent prognostic factor.
AB  - OBJECTIVES: Cytokines are potential new serum markers, especially desirable for
      malignancies with poor prognosis like non-small cell lung cancer (NSCLC).
      METHODS: Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6
      and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1
      receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic
      fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony
      stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA),
      squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera
      of 103 untreated NSCLC patients, and these cytokines and tumor markers were
      referred to clinical parameters of the disease and to the overall survival of
      patients evaluated during a 6-year follow-up. RESULTS: Most of the factors
      analyzed were found to be elevated in the sera of NSCLC patients, and increases
      in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I
      patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than
      the standard tumor markers; IL-6 and IL-1ra levels were significantly different
      in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related
      to the tumor size, while IL-6 and M-CSF levels significantly increased with
      disease progression. A significant prognostic value of pretreatment serum M-CSF
      and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an
      independent prognostic factor. CONCLUSIONS: Increased pretreatment serum M-CSF
      level is a significant independent predictor of poor survival in patients with
      NSCLC.

PMID- 16645325
TI  - Expression of polo-like kinase 1 (PLK1) protein predicts the survival of patients
      with gastric carcinoma.
AB  - OBJECTIVE: To assess the prognostic value of polo-like kinase 1 (PLK1), an
      important regulator of cell cycle progression, in patients with gastric
      carcinoma. METHODS: PLK1 expression was determined in 160 gastric carcinoma
      patients by immunohistochemistry and compared with p53 expression and the
      proliferating cell nuclear antigen-labeling index (PCNA-LI) to evaluate the
      effect of PLK1 on tumor progression. Furthermore, PLK mRNA expression was
      determined in 26 advanced gastric cancer patients by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: PLK mRNA expression was detected in
      25 (96.2%) patients by RT-PCR. Immunohistochemical staining revealed PLK1
      expression in 84 (52.5%) patients. There were no significant relationships
      between PLK1 expression and various clinicopathological factors. PLK1 expression
      was significantly correlated with the PCNA-LI, but not p53 expression. The
      prognosis of patients with PLK1-positive tumors was significantly worse than that
      of patients with PLK1-negative tumors (p < 0.05). Moreover, multivariate analysis
      revealed that PLK1 expression was an independent prognostic factor. Patients with
      PLK1-positive and high PCNA-LI tumors showed a significantly poorer prognosis
      than patients with PLK1-negative and/or low PCNA-LI tumors. Furthermore, the
      prognosis of patients with PLK1- and p53-positive tumors was significantly worse
      than that of patients with PLK1- and p53-negative or PLK1-negative and p53
      positive tumors. CONCLUSION: PLK1 expression may be a critical indicator of a
      poor prognosis in patients with gastric carcinoma.

PMID- 16645326
TI  - A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients
      with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas.
AB  - Only a few drugs are active in the treatment of well-differentiated endocrine
      carcinomas (WDEC). We evaluated the combination of the so-called 'de Gramont
      schedule' and irinotecan in these tumors in a phase II study. METHODS: 20
      patients were enrolled in the study. The combination regimen included irinotecan,
      180 mg/m(2) on day 1, followed by 200 mg/m(2) folinic acid in a 2-hour infusion,
      an intravenous 10-min bolus of 400 mg/m(2) 5-fluorouracil (5FU) and finally 600
      mg/m(2) 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2.
      Clinical, biological and morphological parameters were assessed by CT every 8
      weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3
      cases and other sites in 7 cases. Sixteen patients had previously received
      chemotherapy, and 6 of them had had two lines of treatment. Six patients had
      previously been treated with chemoembolization. RESULTS: The median number of
      cycles administered was 8. Grade 3-4 neutropenia was observed in 8 patients, and
      1 patient experienced febrile neutropenia. There was no toxicity-related death.
      No complete symptomatic response was observed in 7 evaluable patients; 4 patients
      had an objective biological response. One patient achieved a morphological
      objective response, stabilization was observed in 15, but progression occurred in
      3 patients. Median survival was 15 months. CONCLUSION: The above-mentioned
      combination of LV5FU2 + irinotecan does not yield major activity in heavily
      pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant
      toxicity was observed.

PMID- 16645327
TI  - Reduced incidence of severe palmar-plantar erythrodysesthesia and mucositis in a
      prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40
      mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer.
AB  - PURPOSE: The aim of this study was to assess whether the reduction in the total
      dose of pegylated liposomal doxorubicin (PLD) per cycle from 50 mg/m(2) every 4
      weeks to 40 mg/m(2) every 4 weeks can effectively lower the incidence of
      treatment-related palmar-plantar erythrodysesthesia (PPE) and mucositis. METHODS:
      Patients received PLD 40 mg/m(2) every 4 weeks, and were evaluated for toxicity
      prior to each treatment and for response every 8 weeks. RESULTS: All patients
      were previously treated with at least one chemotherapy regimen for metastatic
      disease, and 72% of the patients had a prior exposure to an anthracycline. Forty
      six evaluable patients received a median of four PLD cycles, with a median dose
      intensity of 10 mg/m(2)/week and a median cumulative dose of 160 mg/m(2). No
      National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 PPE was
      observed in these patients. NCI-CTC grade 3 or 4 mucositis occurred in 4.3% of
      patients, only. Response rates and survival results observed here were comparable
      to those observed with PLD 50 mg/m(2) every 4 weeks in a matched patient
      population. However, patients treated with PLD 40 mg/m(2) every 4 weeks
      experienced less PPE and mucositis and required clearly less dose reductions and
      treatment delays. CONCLUSION: The favorable safety profile observed in this study
      leads us to recommend the use of PLD 40 mg/m(2) every 4 weeks for patients with
      advanced breast cancer.

PMID- 16645328
TI  - Zoledronic acid (Zometa) enhances the cytotoxic effect of gemcitabine and
      fluvastatin: in vitro isobologram studies with conventional and nonconventional
      cytotoxic agents.
AB  - OBJECTIVES: To identify synergistic combinations of clinically available agents
      with zoledronic acid which would enhance antitumor activity as measured by median
      effect isobologram analysis and apoptosis assays in vitro. METHODS: The
      interaction of zoledronic acid as a doublet with either carboplatin, cisplatin,
      5'DFUR, docetaxel, epirubicin, fluvastatin, gemcitabine, imatinib, paclitaxel,
      trastuzumab, or vinorelbine was studied in a 72-hour in vitro system using
      defined human cancer cell lines grown as a monolayer in exponential phase. Drug
      effect on growth was measured by a standard MTT assay. Median effect isobologram
      analysis was applied to the results to determine the presence of synergism,
      additive effects, or antagonism of drug combinations. Synergistic combinations
      were also assayed by a cytoplasmic histone-associated DNA fragmentation apoptosis
      assay to verify that the effect was not cytostatic. RESULTS: Zoledronic acid with
      gemcitabine demonstrated global cytotoxic synergy across 7 of 8 cell lines.
      Clinically achievable concentrations of fluvastatin with zoledronic acid also
      demonstrated synergy in 7 of 8 cell lines. All the breast cancer cell lines were
      sensitive. Zoledronic acid and epirubicin were antagonistic in all 4 breast cell
      lines studied. CONCLUSIONS: Combinations of zoledronic acid with either
      gemcitabine or fluvastatin may have a therapeutic role in treatment of bone
      metastasis of selected malignancies.

PMID- 16645329
TI  - Phase II trial of docetaxel therapy in patients with advanced hepatocellular
      carcinoma.
AB  - OBJECTIVES: We assessed the safety and efficacy of docetaxel, a microtubule
      inhibitor, in patients with advanced hepatocellular carcinoma (HCC). METHODS: HCC
      patients that were not suitable for local therapy, but who possessed measurable
      disease, good performance status and adequate organ function were eligible.
      Docetaxel was administered every 3 weeks at a dose of 100 mg/m(2) (or 75 mg/m(2)
      if transaminase levels were between 1.5 and 3.5 times the upper normal limit).
      Efficacy was assessed radiologically every three cycles of chemotherapy. RESULTS:
      Fifteen patients were enrolled: 11 males and 4 females; their median age was 64
      years (range, 42-72 years). Nine patients had underlying cirrhosis. Four patients
      had been surgically treated before relapse (liver resection in 3 cases and
      transplantation in 1), 3 had been treated with arterial chemoembolization and 1
      with arterial chemotherapy (doxorubicin). A total of 57 cycles of docetaxel were
      delivered (median 3, range 1-6). Significant toxicity was observed: mostly grade
      3-4 neutropenia and fatigue (6 and 4 patients, respectively). Treatment had to be
      stopped because of toxicity in 6 patients, all having underlying cirrhosis. An
      important partial response was obtained in 1 patient, a result that enabled liver
      transplantation; this patient is still alive after 34 months. Five patients had
      transient stable disease. CONCLUSION: When used in this schedule, docetaxel does
      not appear to be safe and effective enough in patients with advanced HCC and
      cirrhosis.

PMID- 16645330
TI  - Delta-sleep-inducing peptide potentiates anticonvulsive activity of valproate
      against metaphit-provoked audiogenic seizure in rats.
AB  - The effect of delta-sleep-inducing peptide (DSIP) on the anticonvulsive activity
      of a nonprotective valproate (VPA) dose in a metaphit model of generalized,
      reflex audiogenic seizures in adult Wistar rats was studied. The animals that
      received metaphit (10 mg/kg) were exposed to audiogenic stimulation (100 +/- 3
      dB, 60 s) at hourly intervals. Metaphit-treated rats displaying seizures in 8
      previous tests were i.p. injected with VPA (50 mg/kg) or DSIP (1.0 mg/kg) or
      their combination. Latency to seizure was behaviorally assessed. The EEGs and
      power spectra were recorded and analyzed. Neurotoxicity was evaluated by the
      chimney test. DSIP or VPA alone expressed no significant effect on the latency
      duration, but their combination significantly prolonged latency to seizure during
      6 h after injection, while inducing no significant motor impairment. Neither the
      applied drugs nor their combination abolished metaphit-provoked EEG epileptiform
      activity. The results show that DSIP potentiated anticonvulsive effects of a
      nonprotective VPA dose in a metaphit model of audiogenic seizures without
      influencing its neurotoxicity.

PMID- 16645331
TI  - Immunohistochemical study of caveolin-1 and -2 in the rat retina.
AB  - The expression of caveolin-1 and -2 in the retina was examined; Western blot
      analysis showed that both were present. Immunohistochemistry indicated that
      caveolin-1 was expressed in the majority of retinal layers, including the
      ganglion cell layer, inner plexiform layer, outer plexiform layer, and in the
      vascular endothelial cells of the retina. Caveolin-2 was primarily immunostained
      in the vessels, but in a few other elements as well. This is the first
      demonstration of caveolin differential expression in the retina of rats, and
      suggests that caveolin plays an important role in signal transduction in glial
      cells and neuronal cells.

PMID- 16645332
TI  - Topical application of epidermal growth factor accelerates wound healing by
      myofibroblast proliferation and collagen synthesis in rat.
AB  - Recombinant human epidermal growth factor (rhEGF) stimulates the proliferation
      and migration of epithelial cells in human cell culture systems and animal models
      of partial-thickness skin wounds. This study investigated the effect of a topical
      rhEGF ointment on the rate of wound healing and skin re-epithelialization in a
      rat full thickness wound model, and verified whether or not the rhEGF treatment
      affected both myofibroblast proliferation and collagen synthesis in the dermis.
      When rhEGF (10 microgram/g ointment) was applied topically twice a day for 14
      days, there was significantly enhanced wound closure from the 5th to the 12th day
      compared with the control (ointment base treatment) group. A histological
      examination at the postoperative 7th day revealed that the rhEGF treatment
      increased the number of proliferating nuclear antigen immunoreactive cells in the
      epidermis layer. In addition, the immunoreactive area of alpha-smooth muscle
      actin and the expression of prolyl 4-hydroxylase were significantly higher than
      those of the control group. Overall, a topical treatment of rhEGF ointment
      promotes wound healing by increasing the rate of epidermal proliferation and
      accelerating the level of wound contraction related to myofibroblast
      proliferation and collagen deposition.

PMID- 16645333
TI  - Development of immunoassays for the detection of kanamycin in veterinary fields.
AB  - Monoclonal antibody against kanamycin was prepared, and competitive direct ELISA
      and immunochromatographic assay were developed using the antibody to detect
      kanamycin in animal plasma and milk. The monoclonal antibody produced was
      identified to be IgG1, which has a kappa light chain. No cross-reactivity of the
      antibody was detected with other aminoglycosides, indicating that the monoclonal
      antibody was highly specific for kanamycin. Based on competitive direct ELISA,
      the detection limits of kanamycin were determined to be 1.1 ng/ml in PBS, 1.4
      ng/ml in plasma, and 1.0 ng/ml in milk. The concentration of intramuscularly
      injected kanamycin was successfully monitored in rabbit plasma with competitive
      direct ELISA. Based on the colloidal gold-based immunochromatographic assay, the
      detection limits of kanamycin were estimated to be about 6-8 ng/ml in PBS,
      plasma, and milk. The immunochromatographic assay would be suitable for rapid and
      simple screening of kanamycin residues in veterinary medicine. Screened positives
      can be confirmed using a more sensitive laboratory method such as competitive
      direct ELISA. Therefore, the assays developed in this study could be used to
      complement each other as well as other laboratory findings. Moreover, instead of
      slaughtering the animals to obtain test samples, these methods could be applied
      to determine kanamycin concentration in the plasma of live animals.

PMID- 16645334
TI  - Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves
      (Bubalus bubalis).
AB  - The pharmacokinetics and dosage regimen of cefotaxime following its single
      subcutaneous administration (10 mg/kg) were investigated in buffalo calves.
      Plasma and urine samples were collected over 10 and 24 h post administration,
      respectively. Cefotaxime in plasma and urine was estimated by microbiological
      assay technique using E. coli as test organism. The pharmacokinetic profiles
      fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48
      +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The
      absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/-
      0.02 h, respectively. The apparent volume of distribution and total body
      clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The
      urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total
      administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in
      buffalo calves would be 13 mg/kg repeated at 12 h intervals.

PMID- 16645335
TI  - Effect of Fasciola gigantica excretory secretory antigen on rat hematological
      indices.
AB  - The present study was undertaken to investigate the effect of Fasciola gigantica
      excretory secretory antigen (Fg-ESA) on rat hematological indices. Fg-ESA was
      prepared by keeping thoroughly washed 40 F. gigantica flukes in 100 ml phosphate
      buffer saline (PBS) for 2 h at 37 degrees C, and centrifuging the supernatant at
      12,000 g at 4 degrees C for 30 min. The protein content of Fg-ESA was adjusted to
      1.8 mg/ml. The rats were randomly divided into two groups of six rats each. Rats
      in group A received 0.5 ml of Fg-ESA intraperitoneally (i.p.) for 7 days, whereas
      control rats in group B received 0.5 ml of PBS i.p. for 7 days. Hemograms of both
      groups were studied initially and on days 0, 2, 4, 14 and 21 after the final
      injection of Fg-ESA or PBS. Progressive and significant (p < 0.01) declines in
      the values of hemoglobin, hematocrit, and total erythrocyte count were observed
      without significant (p > 0.05) changes in the values of mean corpuscular
      hemoglobin, mean corpuscular hemoglobin concentration, or mean corpuscular volume
      in group A. Thus, we conclude that Fg-ESA induces normocytic normochromic anemia
      in rats.

PMID- 16645336
TI  - Excitability scores of goats administered ascorbic acid and transported during
      hot-dry conditions.
AB  - In this study, we investigated the effect of ascorbic acid (AA) administration on
      goat excitability due to transportation. Ten goats administered AA (p.o.) at 100
      mg/kg of body weight before transportation served as the experimental group, and
      seven goats administered only 10 ml/kg of sterile water (p.o.) served as
      controls. Excitability scores were recorded for each goat; when weighed, before,
      immediately after, and 3 h after 8 h of transportation. A score of one to four
      was allocated to each goat; higher scores represent greater excitability.
      Immediately after transportation, excitability scores decreased significantly,
      especially those of control goats (p < 0.001). At 3 h posttransportation, the
      excitability scores of animals in the experimental group were not significantly
      (p > 0.05) different from their pre-transportation normal values, whereas those
      of control goats were significantly lower (p < 0.01). The correlation i.e. the
      relationship between excitability score values and percent excitability
      (percentage of goat with particular excitability score) for different
      excitability score group 3 h post-transportation was positive and highly
      significant (p < 0.001), in both experimental and control goats. Our results
      indicate that road transportation induces considerable stress (depression) in
      goats as evidenced by a lower excitability score posttransportation. Moreover,
      the administration of AA pretransportation facilitated the transition from a
      state of depression to excitation. In conclusion, AA administration to animals
      prior to transportation may ameliorate the depression often encountered after
      road transportation.

PMID- 16645337
TI  - Neuropharmacological effects of deltamethrin in rats.
AB  - This study examined the effect of deltamethrin on some of the
      neuropharmacological paradigms in a rat brain such as the motor co-ordination
      test using a rotarod, the pentobarbitone-induced sleeping time and
      pentylenetetrazole (PTZ)-induced convulsion as well as the gamma aminobutyric
      acid (GABA) level. Albino Wistar rats were used as the experimental animals.
      Different neuropharmacological paradigms such as the motor co-ordination by the
      rotarod, pentobarbitone-induced sleeping time and the PTZinduced convulsion were
      examined after administering deltamethrin orally at two doses, 150 mg/kg (LD50)
      and 15 mg/kg (1/10 LD50). The GABA level in the rat brain was estimated by HPLC
      after a single oral dose of 150 mg/kg deltamethrin. Deltamethrin significantly
      reduced the motor coordination, decreased the onset time and increased the
      sleeping time duration induced by pentobarbitone. In addition, it also decreased
      the onset time and increased the duration of convulsions induced by PTZ at 150
      mg/kg (LD50) and 15 mg/kg (1/10 LD50), respectively. Further deltamethrin
      administration decreased the GABA levels in the cerebellum as well as in the
      whole brain (except the cerebellum) significantly at the LD50 dose level. There
      was some correlation between the effect of deltamethrin on the central GABA
      levels and its neuropharmacological effects.

PMID- 16645338
TI  - Experimental peritonitis induced by oral administration of indomethacin in
      Mongolian gerbils.
AB  - The possibility of inducing peritoneal inflammation in three murine species
      (gerbils, rats and mice) via the oral administration of indomethacin was
      investigated with the overall aim of developing an experimental animal model for
      human peritonitis. Gerbils given high doses of indomethacin at a rate of 30 mg
      and 40 mg/kg body weight showed swelling of the abdomen, depression and dyspnea
      within 4 days after the treatment. The severity of the clinical symptoms
      increased with time. The animals were confirmed as having developed peritonitis
      based on the pathological features including inflammation of the peritoneum, and
      fibrinous adhesion of the abdominal organs in the abdominal cavity. The severity
      of peritonitis increased with increasing dose of indomethacin, and was not
      related to the gender of the animal. On the other hand, peritoneal inflammation
      did not develop in the rats and mice even at high doses. Therefore, the
      administration of 30 mg/kg body weight of indomethacin is an effective and simple
      method of inducing peritonitis in 5-week-old Mongolian gerbils. The animal
      peritonitis model used in this study can be used as an effective tool for
      examining potential therapeutic compounds for preventing peritoneal damage during
      peritonitis, and provide insight into the pathophysiology of peritonitis.

PMID- 16645339
TI  - Alteration of nitrergic neuromuscular transmission as a result of acute
      experimental colitis in rat.
AB  - Nitric oxide (NO) is a non-adrenergic, non-cholinergic neurotransmitter found in
      the enteric nervous system that plays a role in a variety of enteropathies,
      including inflammatory bowel disease. Alteration of nitrergic neurons has been
      reported to be dependent on the manner by which inflammation is caused. However,
      this observed alteration has not been reported with acetic acid-induced colitis.
      Therefore, the purpose of the current study was to investigate changes in
      nitrergic neuromuscular transmission in experimental colitis in a rat model.
      Distal colitis was induced by intracolonic administration of 4 % acetic acid in
      the rat. Animals were sacrificed at 4 h and 48 h postacetic acid treatment.
      Myeloperoxidase activity was significantly increased in the acetic acid-treated
      groups. However, the response to 60 mM KCl was not significantly different in the
      three groups studied. The amplitude of phasic contractions was increased by
      Nomega-nitro-L-arginine methyl ester (L-NAME) in the normal control group, but
      not in the acetic acid-treated groups. Spontaneous contractions disappeared
      during electrical field stimulation (EFS) in normal group. However, for the
      colitis groups, these contractions initially disappeared, and then reappeared
      during EFS. Moreover, the observed disappearance was diminished by L-NAME; this
      suggests that these responses were NO-mediated. In addition, the number of NADPH
      diaphorase positive nerve cell bodies, in the myenteric plexus, was not altered
      in the distal colon; whereas the area of NADPH-diaphorase positive fibers, in the
      circular muscle layer, was decreased in the acetic acidtreated groups. These
      results suggest that NO-mediated inhibitory neural input, to the circular muscle,
      was decreased in the acetic acid-treated groups.

PMID- 16645340
TI  - Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly
      administered cefepime in rabbits.
AB  - This study examined the effect of experimentally induced fever on the
      pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six
      rabbits. The study was carried out in two consecutive phases separated by a two
      week washout period. An infection was induced by an intravenous inoculation of 5
      x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic
      investigation. A quantitative microbiological assay was employed to measure the
      plasma cefepime concentrations using an agar-gel diffusion method with Bacillus
      subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection,
      the rectal temperature in the infected animals increased by 1 degrees C. There
      was a significant reduction in the elimination halflife by 21.8 % in the febrile
      rabbits compared to healthy animals. In addition, the infection significantly
      increased the peak plasma concentrations by 11.9 %, the mean residence time by
      19.9 %, the area under the plasmaconcentration-time curve by 53.6 % and the area
      under the moment curve by 62.3 %. In conclusion, the endotoxin-induced febrile
      state produced significant changes in the plasma levels as well as some of the
      pharmacokinetic variables of cefepime in rabbits.

PMID- 16645341
TI  - Modulatory effects of chitosan adipate on the T and B lymphocyte subsets in mice.
AB  - This study examined the subsets of T lymphocytes in the thymus, spleen and
      mesenteric lymph nodes as well as the subsets of B lymphocytes in the spleen and
      mesenteric lymph nodes in mice administered chitosan adipate (20 mg/kg)
      intraperitoneally once or four times at 24 h intervals. The results showed that
      chitosan adipate decreased the percentage of immature CD4+CD8+ thymic T cells and
      increased the percentage of mature CD4+ and CD8+ thymocytes. The most significant
      stimulating effect was observed after four injections. A single exposure to
      chitosan adipate increased the percentage of CD4+ mesenteric lymph node cells,
      but four injections of the drug increased the percentage of CD4+ and CD8+
      mesenteric lymph node cells. Chitosan adipate had no effect on the subset of
      splenic T cells. In contrast, chitosan adipate administered either once or four
      times increased the percentage of CD19+ splenocytes but had no effect on the
      percentage of CD19+ mesenteric lymph node cells. Overall, chitosan adipate
      induces the maturation and differentiation of thymocytes, and regulates the
      number of B splenic cells and lymph node T cells irrespective of the number of
      doses.

PMID- 16645342
TI  - Advancing parity is associated with high milk production at the cost of body
      condition and increased periparturient disorders in dairy herds.
AB  - The objectives of this study were to determine the effects of parity on milk
      production, body condition change, periparturient health, and culling in Korean
      dairy herds. The data utilized included; milk yield, body condition score, cow
      parity, calving condition, periparturient disorders, culling, and reproductive
      status, which were recorded from 1290 calvings in eight dairy herds. The mean
      milk yield in cows over 305 days increased with increasing parity (p < 0.01).
      Cows with parities of 3, 4, and 5 or higher lost more body condition than those
      with a parity of 1 during month 1 of lactation (p < 0.01), and body condition
      recovery by cows with parities of 4 and 5 or higher was slower (p < 0.01) than
      recovery by cows with parities of 1, 2, or 3 until month 3 of lactation. The risk
      of retained placenta, metabolic disorder, and endometritis also increased with
      advancing parity (p < 0.05). Moreover, the incidence of ovarian cysts was lower
      in cows with a parity of one than in cows with greater parities (p < 0.01).
      Culling rate due to reproductive failure also increased with advancing parity (p
      < 0.01). These results suggest that parity increases milk yield, body condition
      loss during early lactation, the risk of periparturient disorders, and culling
      due to reproductive failure in dairy herds.

PMID- 16645343
TI  - Characterization of Chinook head salmon embryo phenotypes of infectious salmon
      anemia virus by real-time RT-PCR.
AB  - We have previously described the development of a onetube SYBR Green real-time RT
      PCR assay for the detection and quantitation of infectious salmon anemia virus
      (ISAV) in various biological samples. The twofold aim of the present study was to
      verify that the optimized SYBR Green real-time RT-PCR conditions could detect
      ISAV isolates of different geographic origins, and to analyze the growth patterns
      of the selected ISAV isolates in the Chinook head salmon embryo (CHSE) -214 cells
      by this assay to better characterize their CHSE-phenotypes. A total of 24 ISAV
      isolates were used in this study. The results indicated that the SYBR Green real
      time RT-PCR could detect ISAV of different geographic origins or laboratory
      sources. The capacity of ISAV isolates to cause cytopathic effects (CPE) in the
      CHSE-214 cell line, viral titration of the infected CHSE-cell harvests, and
      analysis of viral RNA levels in CHSE-214 cells at post-infection day zero, 7 and
      14 by SYBR Green real-time RT-PCR confirmed the existence of three CHSE
      phenotypes of ISAV: replicating cytopathic, replicating non-cytopathic, and non
      replicating non-cytopathic. The identification of these three CHSE- phenotypes of
      ISAV has important implications from diagnostic and biological points of view.

PMID- 16645344
TI  - Evaluation of a Bacillus stearothermophilus tube test as a screening tool for
      anticoccidial residues in poultry.
AB  - A Bacillus stearothermophilus var. calidolactis C953 tube test was evaluated for
      its ability in detecting the residue of selected anticoccidial drugs in poultry,
      specially sulfamethazine, furazolidone, and amprolium. Various concentrations of
      each drug were injected into chicken liver and kidney tissues and these tissues
      were tested to determine the drug detection limits for each drug. The detection
      limit was defined as the drug concentration at which 95 % of the test results
      were interpreted as positive. The limits of detection in liver tissue were 0.35
      microgram/ml for furazolidone, 0.70 microgram/ml for sulfamethazine and 7.80
      microgram/ml for amprolium. In kidney tissues, they were 0.30 microgram/ml for
      furazolidone, 0.54 microgram/ml for sulfamethazine, and 7.6 microgram/ml for
      amprolium. It was concluded that this tube test could be used to screen for the
      residue of these three drugs in poultry.

PMID- 16645345
TI  - Random amplified polymorphic DNA (RAPD) analysis of Mycobacterium tuberculosis
      strains in India.
AB  - The usefulness of random amplification of polymorphic DNA (RAPD) analysis for
      typing Indian strains of M. tuberculosis was investigated. M. tuberculosis H37Rv,
      M. tuberculosis DT and 42 clinical isolates of M. tuberculosis were subjected to
      RAPD-PCR using 7 random decamer primers. All 7 primers were found to be
      differentiated and produced specific RAPD profiles. The polymorphic amplicons
      served as RAPD markers for M. tuberculosis. The dendrograms, obtained by
      different primers, showed the discriminatory ability of the primers. RAPD
      analysis provided a rapid and easy means of identifying polymorphism in M.
      tuberculosis isolates, and it was found to be a valuable alternative
      epidemiological tool. In addition, the results of the present study showed
      heterogeneity in the M. tuberculosis strains in the population studied.

PMID- 16645346
TI  - Matricaria chamomilla CH12 decreases handling stress in Nelore calves.
AB  - Matricaria chamomilla CH12 is a phytotherapeutic or homeopathic product, which
      has been used to reduce stress. Here, we examined its effect on preventing
      handling stress in bovines. Sixty Nelore calves were randomly distributed into
      two equal groups. One group was administered Matricaria chamomilla CH12 in diet
      and the other the 'control' was not. Animals in both groups were maintained
      unstressed for 30 days to adjust to the feeding system and pasture, and were then
      stressed by constraint on the 31th, 38th, 45th and 60th experimental days. Blood
      samples were taken on these days after animals had been immobilization in a trunk
      contention for 5 min. Stress was followed by analyzing serum cortisol levels.
      These peaked on the 45th day and then decreased, but not to baseline, on the 60th
      day. On the 45th day cortisol levels were significantly lower in animals fed
      Matricaria chamomilla CH12, suggesting that this product reduces stress. These
      effects may be a consequence of its inhibiting cortisol production and its
      calming and anxiolytic effects.

PMID- 16645347
TI  - Echocardiographic indices in normal German shepherd dogs.
AB  - Sixty clinically normal German shepherd dogs, 31 males and 29 females, ranging in
      age from 1 and 5 years and with a body weight ranging from 22 to 37.2 kg, were
      examined by the two-dimensional mode, M-mode, and Doppler echocardiography. In
      Doppler mode, the mitral valve flows were obtained, where the aim was to
      determine the velocity peaks and ratios of the E and A waves and the mitral E
      wave deceleration time. The velocity peaks were obtained for the tricuspid,
      pulmonary and aortic valves. On the left ventricular outflow tract flow, the time
      velocity integral and aortic cross-sectional area was used to calculate the
      cardiac output. A statistically significant correlation with the body weight was
      found for the systolic left atrial and diastolic aortic diameter on two
      dimensional mode. On M-mode, there was a significant correlation between the body
      weight and the systolic left atrium and diastolic aortic dimension, systolic and
      diastolic left ventricular, septal and posterior wall dimensions. Doppler
      echocardiography showed that there was no significant correlation between the
      body weight and the mitral, tricuspid, pulmonary and aortic valves flows. These
      results demonstrate that it is important to know the normal echocardiographic
      values for German shepherd dogs because there are some characteristics peculiar
      to this particular breed. The data obtained is expected to be helpful for studies
      on small animal cardiology.

PMID- 16645348
TI  - Mediastinal lymphoma in a young Turkish Angora cat.
AB  - An 8-month old intact male Turkish Angora cat was referred to the veterinary
      Medical Teaching Hospital (VMTH), Seoul National University, for an evaluation of
      anorexia and severe dyspnea. The thoracic radiographs revealed significant
      pleural effusion. A cytology evaluation of the pleural fluid strongly suggested a
      lymphoma containing variable sized lymphocytes with frequent mitotic figures and
      prominent nucleoli. The feline leukemia virus and feline immunodeficiency virus
      tests were negative. The cat was euthanized at his owner's request and a necropsy
      was performed. A mass was detected on the mediastinum and lung lobes. A
      histopathology evaluation confirmed the mass to be a lymphoma.
      Immunohistochemistry revealed the mass to be CD3 positive. In conclusion, the cat
      was diagnosed as a T-cell mediastinal lymphoma.

PMID- 16645349
TI  - Application of ventriculoperitoneal shunt as a treatment for hydrocephalus in a
      dog with syringomyelia and Chiari I malformation.
AB  - A twenty-month-old Chihuahua male dog was presented to us suffering with ataxia.
      Based on the physical examination, X-ray and magnetic resonance imaging (MRI)
      examinations, we diagnosed the dog with hydrocephalus, Chiari I malformation and
      syringomyelia. Treatment consisted of internal medical treatment and the
      placement of a ventriculoperitoneal (VP) shunt. The ventricular dilatation was
      relieved and the dog improved neurologically; however, the Chiari I malformation
      and syringomyelia remained after surgically positioning the VP shunt.

PMID- 16645350
TI  - Balantidiasis in the gastric lymph nodes of Barbary sheep (Ammotragus lervia): an
      incidental finding.
AB  - A 4-year-old female Barbary sheep (Ammotragus lervia) was found dead in the
      Gwangju Uchi Park Zoo. The animal had previously exhibited weakness and lethargy,
      but no signs of diarrhea. The carcass was emaciated upon presentation. The main
      gross lesion was characterized by severe serous atrophy of the fat tissues of the
      coronary and left ventricular grooves, resulting in the transformation of the fat
      to a gelatinous material. The rumen was fully distended with food, while the
      abomasum evidenced mucosal corrugation with slight congestion. Microscopic
      examination revealed the presence of Balantidium coli trophozoites within the
      lymphatic ducts of the gastric lymph node and the abdominal submucosa. On rare
      occasions, these organisms may invade extra-intestinal organs, in this case the
      gastric lymph nodes and abomasum.

PMID- 16645351
TI  - "Back to the future" with the Journal of Cardiovascular Medicine (formerly
      Italian Heart Journal)!

PMID- 16645352
TI  - Welcome address: From the President.

PMID- 16645353
TI  - The drug-eluting stent dilemma: comparing the effectiveness of Cypher versus
      Taxus.

PMID- 16645354
TI  - Effectiveness of continuous infusions of loop diuretics for severe heart failure.
AB  - Heart failure is a growing worldwide epidemic resulting in frequent
      hospitalizations and increased resource utilization. A major cause of
      hospitalization is congestive symptoms and impaired functional capacity due to
      sodium and water retention. Diuretic resistance, which is common among patients
      with severe heart failure, may inhibit diuresis, thus prolonging
      hospitalizations. The current evidence suggests that continuous infusions are a
      potentially effective method for delivering high daily doses of diuretics and
      rapidly removing large amounts of excess sodium and water. In our experience,
      continuous intravenous infusions of furosemide are well tolerated and may shorten
      hospitalizations, which in turn reduces overall costs. Although the current
      evidence is largely limited to observational reports and small uncontrolled
      studies, the consistent findings of efficacy and safety warrant the further
      investigation of this treatment strategy in randomized controlled trials.

PMID- 16645355
TI  - Aortic dilatation in patients with bicuspid aortic valve.
AB  - The association of a bicuspid aortic valve (BAV) with abnormalities of the
      proximal thoracic aorta, including dilatation, aneurysm and dissection, has been
      previously described, leading to the hypothesis of a common underlying
      developmental defect involving the aortic valve and the aortic wall.
      Consequently, any patient with BAV should receive a careful assessment not only
      of the valve function, but also of the aortic root and the ascending aorta.
      Dilatation of the proximal thoracic aorta is a common finding in patients with
      BAV and is believed to be related to aortic rupture and dissection. Because
      progressive dilatation can occur, careful long-term surveillance of the aortic
      dimensions is required. Prophylactic surgical repair of the dilated aorta should
      be recommended more aggressively for patients with BAV than for those with a
      tricuspid aortic valve. However, the optimal timing of aortic surgery in BAV
      patients remains uncertain because of the limited data available on the natural
      history of asymptomatic aortic dilatation.

PMID- 16645356
TI  - Clinical imaging of the vulnerable plaque in the coronary arteries: new
      intracoronary diagnostic methods.
AB  - Rupture of a vulnerable plaque is the main cause of acute coronary syndromes and
      myocardial infarction. The features of rupture-prone atherosclerotic plaques have
      been previously described by pathologists. However, identification of vulnerable
      plaques in vivo is essential to study their natural history and to evaluate
      potential treatment modalities. Coronary angiography is the gold standard for the
      diagnosis of coronary artery disease, but it is unable to distinguish between
      stable and unstable plaques and to accurately predict future cardiac events. This
      current perspective describes the recently developed invasive imaging techniques
      to detect atherosclerotic vulnerable plaques in the coronary tree.

PMID- 16645357
TI  - Rationale and design of the GISSI-Atrial Fibrillation Trial: a randomized,
      prospective, multicentre study on the use of valsartan, an angiotensin II AT1
      receptor blocker, in the prevention of atrial fibrillation recurrence.
AB  - BACKGROUND: The possibility of preventing atrial fibrillation recurrence with
      anti-arrhythmic agents is very limited, given the discouraging results obtained
      with current drugs in many patients. Data from experimental studies suggest that
      angiotensin II AT1-receptor blockers can influence atrial remodelling, a key
      factor in atrial fibrillation initiation and maintenance. Moreover, some
      preliminary clinical data show that angiotensin II AT1 -receptor blockers can
      prevent atrial fibrillation episodes. The GISSI-Atrial Fibrillation (AF) trial is
      a randomized, prospective, parallel group, placebo-controlled, multicentre study
      designed to test whether angiotensin II AT1-receptor blockers can reduce atrial
      fibrillation recurrence. OBJECTIVES AND METHODS: The primary objective of the
      study is to demonstrate that, in patients with a history of recent atrial
      fibrillation who are treated with the best recommended therapies, the addition of
      the angiotensin II AT1-receptor blocker valsartan (titrated up to 320 mg) is
      superior to placebo in reducing atrial fibrillation recurrence. A substudy will
      analyse the effect of valsartan on left atrial dimensions and on neurohormones.
      The study population consists of patients with symptomatic atrial fibrillation
      (at least two electrocardiogram documented atrial fibrillation episodes in the
      previous 6 months or successful cardioversion in the last 2 weeks) with
      underlying cardiovascular diseases or comorbidities. With approximately 100
      centres participating in Italy, a total of 1402 patients are randomized in a 1 :
      1 ratio to receive valsartan or placebo. The enrolment period will last 12 months
      and the patients will be followed for 12 months from study entry. CONCLUSIONS:
      The GISSI-AF is the largest trial aimed at assessing the role of angiotensin
      receptor blockade in reducing the recurrence of atrial fibrillation and its
      possible mechanisms of action in terms of its effects on atrium remodelling and
      neurohormones.

PMID- 16645358
TI  - Seven-year follow-up after catheter ablation of atrioventricular nodal re-entrant
      tachycardia.
AB  - BACKGROUND: Radiofrequency catheter ablation is considered to be a curative
      therapy for patients with atrioventricular nodal re-entrant tachycardia (AVNRT).
      Nevertheless, there is little information available with respect to long-term
      results and the consequences of catheter ablation. The present study aimed to
      assess the long-term results (a minimum of 5 years) and clinical events. PATIENTS
      AND METHODS: The recurrence rate of AVNRT, the development of late
      atrioventricular block and the presence of other arrhythmias (atrial flutter and
      fibrillation) were assessed in 131 consecutive patients who were undergoing
      catheter ablation between January 1992 and December 1998. RESULTS: During a mean
      follow-up of 7.2 +/- 2.5 years, tachycardia recurred in 13 patients (10%) after a
      median time of 6 months (interquartile range 4-24 months) and a second procedure
      was perfomed. Atrioventricular block occurred in two patients (1.5%) after 1 and
      13 months. Atrial fibrillation recurred in seven (44%) of 16 patients in whom
      atrial fibrillation or flutter was present before ablation after a median of 12
      months (interquartile range 9-15 months). Overall, all these events occurred
      after a median of 9 months (interquartile range 4-17 months). Subsequently, no
      event related to the arrhythmia or to the procedure was observed. A new onset
      atrial fibrillation, probably not related to AVNRT, occurred late in the follow
      up in a further three patients. CONCLUSIONS: Arrhythmic events are not infrequent
      after catheter ablation of AVNRT during the early years after ablation, but they
      are unlikely during the subsequent long-term follow-up.

PMID- 16645359
TI  - Effect of the new diagnostic criteria for ST-elevation and non-ST-elevation acute
      myocardial infarction on 4-year hospitalization: an analysis of hospital
      discharge records in the Veneto Region.
AB  - OBJECTIVE: To assess the burden of hospitalization for acute coronary syndrome
      (ACS) and the impact of the new diagnostic criteria for acute myocardial
      infarction on epidemiology of ACSs. METHODS: We analysed the hospital discharge
      record archives of the Veneto Region in the period 2000-2003, including
      admissions of regional residents outside the study area. We defined a list of ICD
      9-CM codes for the identification of different types of ACS. We examined trends
      in standardized hospitalization rates as well as patient characteristics (age,
      sex) and pattern of care (setting, invasive revascularization, length of hospital
      stay, in-hospital mortality). RESULTS: The hospitalization rate for non-ST
      elevation myocardial infarction increased by about 70%, with a parallel decrease
      in hospitalizations for unstable angina, whereas the hospitalization rate for ST
      elevation myocardial infarction remained unchanged. These trends are likely
      influenced by the new diagnostic criteria for acute myocardial infarction. At the
      end of the study period, although the main patient characteristics did not vary
      substantially, the pattern of care turned out to be more aggressive. CONCLUSIONS:
      Despite some limitations, our results indicate that the new diagnostic criteria
      for acute myocardial infarction have a major impact on epidemiological
      evaluation. These data may be relevant when comparing epidemiological data of
      different periods and planning healthcare policies. Further studies are needed in
      order to evaluate the accuracy of ICD-9-CM codes in the diagnosis of ACSs.

PMID- 16645360
TI  - Cardiac imaging improves risk stratification in high-risk patients undergoing
      surgical revascularization.
AB  - OBJECTIVE: In patients with ischaemic left ventricular dysfunction, multivessel
      disease and dominance of necrotic myocardium, perioperative mortality due to
      coronary artery bypass grafting is still a rather unclear issue. The aim of this
      study was to analyse the impact of different imaging variables in predicting
      perioperative mortality. METHODS: We selected a group of 259 patients who had
      preoperatively been defined as 'high-risk patients' and who showed a mostly
      necrotic myocardium as detected by thallium-201 myocardial scintigraphy. RESULTS:
      Mean ejection fraction was 0.26 +/- 0.07. In a 16-segment model, the mean number
      of scintigraphic necrotic myocardial segments was 5.07 +/- 1.09,
      echocardiographic end-diastolic diameter was 29.41 +/- 2.38 mm/m2 and wall motion
      score index was 2.29 +/- 0.19. Perioperative mortality increased along with the
      increase in the number of necrotic segments: 5/105 (5%), 4/63 (6%), 8/52 (15%)
      and 8/39 (20%) patients with four, five, six and seven necrotic segments,
      respectively. The analysis of additional variables in survived vs. deceased
      patients demonstrated a significant difference in echocardiographic end-diastolic
      diameter (27 +/- 8 vs. 31.9 +/- 1.9 mm/m2, P < 0.001) and in wall motion score
      index (2.2 +/- 0.1 vs. 2.4 +/- 0.2, P < 0.001). CONCLUSIONS: In high-risk
      patients, the extension of scintigraphic myocardial scar has a significant impact
      on perioperative mortality. For similar values of ejection fraction at rest,
      additional imaging variables, such as echocardiographic end-diastolic diameter
      and wall motion score index, may contribute to select those patients in whom
      mortality may exceed 15%.

PMID- 16645361
TI  - Minimally invasive mitral valve repair as a routine approach in selected
      patients.
AB  - OBJECTIVE: To report our experience with minimally invasive mitral valve repair.
      METHODS: From 1999 to 2003,104 patients underwent mitral valve repair through a
      right anterolateral minithoracotomy. Most of them were in New York Heart
      Association functional class I-Il, had normal ejection fraction and were in sinus
      rhythm. Eighty-five patients suffered from severe mitral regurgitation due to
      degenerative disease (n = 82) or healed endocarditis (n = 3) and 19 patients had
      severe mitral stenosis. Sixty-two patients underwent edge-to-edge repair due to
      anterior/bileaflet prolapse, 23 had a quadrangular resection of the posterior
      leaflet and 19 a commissurotomy. RESULTS: No conversions to sternotomy were
      necessary. Mean cardiopulmonary bypass and aortic cross-clamp times were 75 +/-
      14 and 54 +/- 8 min, respectively. Median mechanical ventilation and intensive
      care unit stay times were 6 and 13 h, respectively. No in-hospital deaths and no
      major postoperative complications occurred. At a mean follow-up of 27.4 +/- 10.6
      months, all patients but two were in New York Heart Association functional class
      I. The survival rate was 100% and freedom from reoperation was 95.2 +/- 3.3% at 4
      years. No or mild residual mitral regurgitation was detected at echocardiography
      in 100 patients (96%) and moderate insufficiency was found in two (1.9%). The
      degree of satisfaction in terms of cosmetic result and postoperative discomfort
      was very high. CONCLUSIONS: Mitral valve repair can be effectively performed
      through a minimally invasive approach achieving excellent mid-term results and a
      high degree of patient satisfaction in terms of comfort, cosmetic result and
      prompt recovery. At our institution, this approach has now become the standard
      procedure for mitral valve disease in young and active patients.

PMID- 16645362
TI  - Rat carotid arteriotomy: c-myc is involved in negative remodelling and apoptosis.
AB  - OBJECTIVE: c-myc is the main proto-oncogene responsible for restenosis in
      cardiovascular surgery. The aim of our study was to evaluate the effects of c-myc
      antisense (AS) phosphorothioate oligodeoxynucleotides (ODNs) in the remodelling
      process induced by surgical carotid arteriotomy on an experimental rat model.
      METHODS: Fifty-five rats with carotid stenosis and apoptosis induced by
      arteriotomy were submitted to gene expression analysis 4 h after surgery, to
      TUNEL assay 48 h after surgery and to histological analysis 30 days later.
      RESULTS: AS ODNs induced a 60% decrease in target c-myc mRNA in injured carotid
      arteries compared to control sense and scrambled ODN-treated carotid arteries (P
      < 0.05). Histological evaluation revealed that stenosis stimulated by arteriotomy
      was mainly due to adventitial constrictive remodelling rather than to neointimal
      hyperplasia, observed only in a limited number of samples. Morphometric analysis
      showed that lumen area in c-myc AS ODN-treated carotid arteries was 35% greater
      than in control arteries (P < 0.05), whereas the media/lumen area ratio showed a
      63% reduction in AS ODN-treated carotid arteries in comparison to control
      arteries (P < 0.05). Surgical injury affected the expression of apoptosis-related
      genes Bcl-2, Bax, Bcl-xL and Bcl-xS, inducing a mean 3.5-fold decrease in the Bcl
      2/ Bax ratio and a 9-fold decrease in the Bcl-xL/S ratio 4 h after injury as
      compared with uninjured carotid arteries. TUNEL assay experiments revealed
      increased apoptosis in AS ODN-treated carotid arteries in comparison to control
      carotid arteries. CONCLUSIONS: c-myc AS ODNs reduce the negative remodelling
      induced by arteriotomy. The imbalance between proliferative stimulus represented
      by surgery and the c-myc mRNA decrease induced greater apoptosis in AS ODN
      treated carotid arteries without further affecting mRNA levels of Bcl-2, Bax, Bcl
      xL and Bcl-xS genes.

PMID- 16645363
TI  - Spontaneous coronary artery dissection after heavy lifting in a 25-year-old man
      with coronary risk factors.
AB  - Spontaneous coronary artery dissection (SCAD) is a clinical condition rarely
      leading to acute myocardial infarction (AMI). We report the case of SCAD
      presenting AMI in a 25-year-old man with coronary risk factors after strenuous
      exercise, who was successfully treated with systemic thrombolysis. Coronary
      angiography revealed spiral dissection of the proximal part of the left anterior
      descending artery. The present case supports the occurrence of SCAD as a cause of
      AMI in young male patients who have coronary risk factors, after heavy lifting.

PMID- 16645364
TI  - Spontaneous coronary artery dissection: when spontaneous means unknown.

PMID- 16645365
TI  - Late-onset arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial
      pathology usually diagnosed at a young age. Although ARVC is characterized by
      well-known clinical and instrumental features, the diagnosis in older patients
      can sometimes be difficult, due to the frequent left ventricular involvement and
      possible concomitant coronary artery disease. In the present study, we describe
      two female patients in whom morphological and kinetic abnormalities of the right
      ventricle, in keeping with the diagnosis of ARVC, appeared when they were aged in
      their fifties. These two cases indicate that clinical screening should be
      continued throughout adult life in people who are at risk of ARVC.

PMID- 16645366
TI  - 22q11 deletion syndrome: a review of some developmental biology aspects of the
      cardiovascular system.
AB  - The morphology and molecular genetics of the 22q11 deletion syndrome
      cardiovascular anomalies are reviewed. Special emphasis is given to TBX1,
      recently identified and considered to be the potential key gene for this clinical
      syndrome. The TBX1 downstream molecular pathways modulating the normal
      development of the pharyngeal apparatus are also discussed, and emphasis is given
      to the possible, equally fundamental role of downstream molecular pathway
      disruption in causing the clinical 22q11 deletion phenotype features.

PMID- 16645367
TI  - Myocardial preconditioning and cardioprotection by volatile anaesthetics.
AB  - The biological bases and the clinical applications of ischaemic and anaesthetic
      preconditioning are reviewed. Ischaemic preconditioning is an endogenous
      defensive phenomenon of the myocardium in which brief periods of ischaemia
      followed by reperfusion reduce the infarct size induced by longer ischaemic
      stimuli; both an early and a late phase may be distinguished. In the early phase,
      the mediators released activate ATP-dependent potassium channels and kinase
      cascade; these enzymes migrating at the level of various subcellular structures
      phosphorylate some end-effectors responsible for cardioprotection. Several
      molecules that are involved in the regulation of cell death during ischaemia
      reperfusion injury have been proposed for such a role, including mitochondrial
      ATP-dependent potassium channels, connexins and cytoskeletal and mitochondrial
      proteins. In the late phase, the triggers and mediators themselves, plus nitric
      oxide, are responsible for the genetic reprogramming providing a protective
      effect via ex-novo synthesis of proteins. Volatile halogenated anaesthetics may
      induce a particular sort of pharmacological preconditioning, anaesthetic
      preconditioning, which presents some differences in the biochemical signalling
      mechanism but is able to give protection comparable to the ischaemic form.
      Anaesthetic preconditioning presents obvious advantages compared to ischaemic
      preconditioning, and researchers have tried to take advantage of this in the
      clinical setting, in cardiac surgical patients, in neuroprotection and to prolong
      the survival of organs destined for transplantation.

PMID- 16645368
TI  - Medical and surgical treatment of chronic mitral regurgitation.
AB  - Chronic severe mitral regurgitation is a progressive disease that can lead to
      left ventricular dysfunction. New information on the natural history of the
      disease, along with advances in surgical techniques, has changed the roles of
      medical and surgical therapies. There is no well-defined role for medical therapy
      in chronic mitral regurgitation. The goal of the treating physician is therefore
      to identify the optimal timing for surgical intervention. The timing of surgical
      intervention depends primarily on two factors: (i) clinical symptoms and (ii) the
      left ventricular response to volume overload. However, the aetiology of mitral
      regurgitation, the likelihood of surgical repair, the occurrence of atrial
      fibrillation and the presence of pulmonary hypertension, together with the
      haemodynamic response to exercise, are important factors in the optimal surgical
      timing. New concepts in the understanding of the natural history of the disease
      coupled with success of mitral repair have recently resulted in a widespread
      evolution towards earlier surgery.

PMID- 16645369
TI  - Coronary revascularization for non-ST elevation acute coronary syndrome: state of
      the art.
AB  - Immediate as well as early revascularization may be beneficial in patients with
      acute coronary syndromes (ACS) without ST elevation, but has traditionally
      employed as an 'ischemia-guided' strategy. A number of randomized trials
      (including more than 10 000 patients) and observational studies have compared
      routine invasive versus selective invasive treatment in patients with an acute
      coronary syndrome without ST elevation. Most randomized trials are limited by a
      high cross-over rate, whereas observational studies are limited by selection
      bias. Data from registries have demonstrated benefits with an invasive approach.
      The results from randomized trials are less clear regarding mortality reduction,
      although long-term survival after hospital discharge may be better after the
      invasive approach. In the randomized trials, there was a decreased risk of death
      or myocardial infarction after the invasive approach (odds ratio = 0.88, 95%
      confidence interval = 0.76-1.0). Despite the optimal timing of angiography and
      subsequent revascularization, if appropriate, angiography and revascularization
      should be considered in every patient admitted with an ACS without ST elevation,
      particularly in patients with high-risk characteristics, such as ST segment
      depression > 0.1 mV, accelerated angina in the prior 2 months, nitrate use in the
      prior week before admission and elevated troponin.

PMID- 16645370
TI  - Bridge to transplantation with the MicroMed DeBakey ventricular assist device
      axial pump: a single centre report.
AB  - OBJECTIVE: Left ventricular assist devices (VADs) are an accepted therapy to
      bridge patients with end-stage heart failure to heart transplantation. The
      DeBakey VAD, a continuous axial flow pump weighing 93 g, has been introduced into
      clinical practice as a bridge to transplant. METHODS: Starting from April 2000,17
      patients (12 males, five females, mean age 44.3 +/- 12.8 years; 11 dilated
      idiopathic cardiomyopathy, five ischaemic cardiomyopathy, one pulsatile device
      failure) with end-stage heart failure were implanted with a DeBakey VAD as a
      bridge to transplantation at our institution. Before implant, all patients
      suffered from severe heart failure (New York Heart Association functional class
      IV) despite optimal medical therapy and were put on the waiting list for heart
      transplantation. Mean cardiac index was 1.59 +/- 0.51 l/min/m2. RESULTS: Fourteen
      patients were successfully transplanted after 99 +/- 117 days of assistance
      (range 11-443 days). Two patients died during assistance of multiorgan failure,
      one patient is still on VAD. No patient needed additional right ventricular
      mechanical support. Left ventricular/left VAD thrombosis occurred in one patient
      who was successfully treated conservatively. No clinical elevation of plasma free
      haemoglobin was detected. Neither device, driveline, abdominal pocket infection
      nor device failure occurred. CONCLUSIONS: In our experience with the continuous
      axial flow DeBakey VAD, a high success rate was obtained associated with a low
      risk of complications. All the patients tolerated continuous blood flow for
      extended periods that makes this device a valuable alternative to pulsatile VADs
      as a bridge to transplantation.

PMID- 16645371
TI  - Treatment of pulmonary hypertension in patients undergoing cardiac surgery with
      cardiopulmonary bypass: a randomized, prospective, double-blind study.
AB  - OBJECTIVE: Pulmonary hypertension can already be present in patients undergoing
      cardiac surgery or can be exacerbated by cardiopulmonary bypass. Postoperative
      treatment is still a challenge for physicians. The aim of this study was to
      evaluate the effects of inhaled prostacyclin (iPGI2) and nitric oxide (iNO)
      compared with those of intravenous vasodilators. METHODS: This prospective,
      randomized, double-blind study included 58 patients affected by severe mitral
      valve stenosis and pulmonary hypertension with high pulmonary vascular resistance
      (> 250 dynes x s x cm(-5)) and a mean pulmonary artery pressure > 25 mmHg. All
      patients were monitored by central venous, radial arterial and Swan-Ganz
      catheters. Data were recorded at six different time points, before induction of
      anaesthesia, during and after surgery. Prostacyclin and nitric oxide were
      administered by inhalation 5 min before weaning from cardiopulmonary bypass and
      continued in the intensive care unit. Right ventricular function was evaluated by
      transoesophageal echocardiography. RESULTS: Hospital mortality was 3.4%. After
      drug administration, the mean pulmonary artery pressure and pulmonary vascular
      resistance were significantly decreased in the iNO and iPGI2 groups with respect
      to the baseline values (P < 0.05) and such a decrease was maintained throughout
      the study; this was not observed in the control group. In the iNO and iPGI2
      groups we demonstrated a significant increase in cardiac indices and right
      ventricular ejection fraction after drug administration with respect to baseline.
      Furthermore, patients in the inhaled drug groups were weaned easily from
      cardiopulmonary bypass (P = 0.04) and had a shorter intubation time (P = 0.03)
      and intensive care unit stay (P = 0.02) than the control group. CONCLUSIONS: Our
      data suggest that both iNO and iPGI2 are effective in the treatment of pulmonary
      hypertension. iPGI2 has a number of advantages over iNO, including its easy
      administration and lower cost. Intravenous vasodilator treatment, on the other
      hand, is effective in terms of mortality but has a higher morbidity rate.

PMID- 16645372
TI  - Is pretreatment with ibutilide useful for atrial fibrillation cardioversion when
      combined with biphasic shock?
AB  - OBJECTIVE: Cardioversion of atrial fibrillation by means of a monophasic
      transthoracic shock is facilitated by pretreatment with ibutilide. The aim of
      this study was to randomly and prospectively compare the energy requirements of
      transthoracic biphasic cardioversion of atrial fibrillation with and without
      ibutilide pretreatment. METHODS: Fifty patients were enrolled and randomized into
      two groups: immediate cardioversion with biphasic shock (group 1) or ibutilide
      pretreatment followed by cardioversion with biphasic shock (group 2). In group 2,
      ibutilide was administered intravenously in 10 min at a dose of 0.01 mg/kg. A
      pause of 10 min was observed before the patients underwent cardioversion.
      RESULTS: All patients of both groups were successfully cardioverted (100%).
      Energy and number of shocks were significantly lower in group 2 than in group 1
      (P< 0.02). Eleven of 25 patients (44%) in group 1 and 15 of 23 patients (65%) in
      group 2 were cardioverted at the first attempt with 50 J. The number of patients
      cardioverted at the first attempt with 50 J was significantly higher in group 2
      than in group 1 (P = 0.018). CONCLUSIONS: Although not essential for a successful
      outcome, pretreatment with ibutilide can lower energy requirements in
      transthoracic biphasic cardioversion.

PMID- 16645373
TI  - Cardiovascular risk during physical activity in the mountains.
AB  - OBJECTIVE: Several previous studies evaluated the cardiovascular risk associated
      with exercise, but only a few papers considered this risk during physical
      activity in the mountains. The aim of this study was to assess the cardiovascular
      risk in a population practising physical activity in the mountains. METHODS: We
      used an observational study design. We estimated the population by integrating
      the data of presences in the accommodation establishments with data from
      telephone and on-field interviews. As survey sources of cardiovascular events we
      used the reports of the Mountain Rescue teams and of the emergency physicians and
      pathologists operating in the hospitals of the considered mountain area. RESULTS:
      We estimated that the duration of exposure to risk for the study population was,
      averagely per year, 12 449 877 person-days. During the study period, we recorded
      117 cardiovascular events, namely 38 sudden cardiac deaths, 13 acute coronary
      syndromes, and five strokes. The remaining 61 events were non-traumatic events
      with a probable cardiovascular origin. We calculated one cardiovascular event per
      319 000 person-days of physical activity in the mountains, one sudden cardiac
      death per 980 000 and one acute coronary syndrome per 2 895 000 person-days.
      CONCLUSIONS: The risk of cardiovascular events in the population practising
      physical activity in the mountains is very low and essentially limited to men
      over the age of 40, particularly if they do not practise regularly physical
      activity. For these subjects the risk seems to be associated with physical
      activity, but not with altitude and other typical aspects of mountains, such as
      low temperature and difficulties of terrain.

PMID- 16645374
TI  - Coronary artery spasm induced by capecitabine.
AB  - Capecitabine is a new chemotherapeutic agent considered highly specific for
      sensitive tumour cells, which convert the drug to 5-fluorouracil. Capecitabine is
      administered on an ambulatory basis for the treatment of metastatic breast and
      colorectal cancer, and both general practitioners and specialists are likely to
      deal with patients treated with this drug. We describe the case of a 44-year-old
      woman, with no cardiovascular risk factors, who started therapy with capecitabine
      for relapsing of breast carcinoma. She subsequently developed effort angina.
      Standard electrocardiogram and echocardiography were normal, whereas ST-segment
      elevation and angina were induced during exercise stress test. Capecitabine was
      withdrawn and therapy with diltiazem and transdermal nitroglycerine was started.
      The patient became asymptomatic and repeated symptom-limited exercise stress test
      did not induce any ST-segment changes or angina, even after withdrawal of anti
      ischaemic therapy, thus confirming the hypothesis of capecitabine-induced
      coronary artery spasm as the cause of patient's symptoms.

PMID- 16645375
TI  - Effective intracoronary thrombectomy with the X-sizer catheter of the right
      coronary artery and left anterior descending artery in a patient with acute
      inferior and right ventricular infarction complicated by hypotension and diffuse
      intracoronary thrombosis.
AB  - Intracoronary thrombosis of non infarct-related arteries during an episode of
      acute myocardial infarction can be correlated with a general thrombogenic state
      and precipitated by prolonged hypotension. We report the case of a patient with
      acute inferior and right ventricular infarction with acute thrombotic obstruction
      of the proximal right coronary artery and associated sessile thrombus in the
      proximal left anterior descending artery, both successfully treated by
      thromboaspiration with the X-Sizer catheter (ev3, Inc., Plymouth, Minnesota,
      USA).

PMID- 16645376
TI  - Upgrade of a single chamber endo-epicardial to a triple chamber biventricular
      implantable cardioverter-defibrillator.
AB  - In patients with heart failure implanted with conventional pacemakers, cardiac
      resynchronization therapy results in significant benefits. The upgrade of
      previously implanted devices to biventricular pacing may be technically
      challenging. We report one case of upgrade to biventricular pacing and describe
      the related technical implications and the therapeutic solutions adopted.

PMID- 16645377
TI  - High-risk percutaneous coronary intervention using the intracardiac microaxial
      pump 'Impella recover'.
AB  - Patients with multivessel coronary artery disease and severe left ventricular
      dysfunction are considered to be at high risk for percutaneous coronary
      intervention, and often are poor surgical candidates because of severe
      comorbidity. We report a case of high-risk percutaneous coronary intervention in
      a 67-year-old man with a severe left ventricular dysfunction and three-vessel
      coronary artery disease using a novel left ventricular assist device.

PMID- 16645378
TI  - The Titan can help titin: from micro to macro myocardial elasticity.
AB  - Heart failure of different etiologies is due to changes in cardiac structure and
      function. During normal diastolic filling, the passive stretch of the ventricular
      myocardium is modulated by titin, a giant elastic protein that acts as a
      molecular spring and leads to the recapitulation of single cell mechanics at
      global ventricular level. The mechanics of a dilated failing heart are at least
      partially determined by variations in the passive filling properties of the
      myocardium that impair contraction. Current volume reduction surgery is based on
      Laplace's law and obtained by rigid means that may impair diastolic function. We
      postulate that inserting one or more elastic elements at different levels of a
      failing ventricle (the mitral annulus, equator and apex) could improve cardiac
      performance. We describe our invention for the first time by presenting the
      results of two animal experiments.

PMID- 16645379
TI  - Use of glycoprotein IIb/IIIa inhibitors in invasively-treated patients with non
      ST elevation acute coronary syndrome.
AB  - Background In patients with non-ST elevation acute coronary syndrome (NST-ACS)
      that is treated invasively, glycoprotein (GP) IIb/IIIa inhibitors can be used
      either as upstream treatment in a coronary care unit or as downstream provisional
      treatment in selected patients who are undergoing percutaneous coronary
      intervention (PCI). The relative advantage of either strategy is unknown. The
      purpose of this study was to assess 30-day outcome of patients enrolled in a
      prospective NST-ACS registry and treated invasively with either of these two
      therapeutic strategies. Methods Patients treated invasively (coronary
      arteriography within 4 days of admission), in the prospective registry ROSAI-2,
      were divided into two groups according to the upstream use of GPIIb/IIIa
      inhibitors (n = 241), or not (n = 548). In the latter group, 76 (14%) patients
      received GPIIb/IIIa in association with a PCI procedure. Clinical and
      angiographic characteristics as well as in-hospital and 30-day outcome of these
      two groups of patients were compared. Results The two groups were similar with
      respect to age, sex, presence of hypertension, diabetes, number of PCI
      procedures. However, patients treated with upstream GPllb/llla blockers had more
      frequently ST-segment depression (P = 0.002), a high TIMI risk score (P = 0.01)
      and were more frequently admitted to centres with Cath Lab facilities (P =
      0.001). At 30-day follow-up, the composite of death, acute myocardial infarction
      and stroke, as well as major bleeding, was not significantly different between
      the two groups, although it occurred more frequently in patients who received
      upstream GPIIb/IIIa blockers (9.5% versus 5.7% and 1.7% versus 0.2%,
      respectively). By multivariate analysis, diabetes [odds ratio (OR) = 2.22, 95%
      confidence interval (CI) = 1.2-4.09] and a diagnosis on admission of non-Q-wave
      myocardial infarction (OR = 2.0, 95% Cl = 1.10-3.6) were independently related to
      outcome. No additional risk or benefit was related to upstream GPIIb/IIIa
      inhibitor treatment (OR = 1.5, 95% Cl = 0.84-2.68). Conclusions Among invasively
      treated patients with NST-ACS, upstream treatment with GPIIb/IIIa inhibitors was
      used in those with a higher clinical risk profile, whereas downstream treatment
      was reserved for a limited number of patients undergoing PCI. Thirty-day outcome
      was similar in the two groups, irrespective of the treatment strategy used.

PMID- 16645380
TI  - Proper use of glycoprotein IIb/IIIa inhibitors in patients with non-sT elevation
      acute coronary syndromes undergoing coronary angiography: frankly, my dear, I
      don't give a damn.

PMID- 16645381
TI  - Performing versus deferring coronary angioplasty based on functional evaluation
      of vessel stenosis by pressure measurements: a clinical outcome study.
AB  - AIM: The present study aimed to prospectively evaluate whether application of the
      concept of fractional flow reserve (FFR) guides the immediate decision to perform
      or to defer coronary angioplasty in unselected consecutive patients with one or
      more angiographically intermediate (50-70%) stenoses and non-conclusive or
      lacking non-invasive testing. METHODS: We studied 112 patients (81 males and 31
      females, aged 31-81 years) including 71 multivessel disease patients (63%) and 30
      patients (27%) with unstable symptoms. FFR was measured with the use of a
      pressure-wire after adenosine-induced hyperaemia and compared with quantitative
      coronary angiography in 171 stenoses. Coronary angioplasty was performed in the
      presence of an FFR < 0.75 and deferred if FFR was > or = 0.75. Cardiac events
      including death, myocardial infarction, recurrent angina or symptoms requiring
      repeated hospitalization and target vessel revascularization (TVR) were recorded
      during a median period of 34 months (interquartile range 9-54 months). RESULTS:
      Coronary angioplasty was deferred based on FFR results in 54 patients (group I).
      In the remaining 58 patients, angioplasty was performed in one or more stenoses
      that were significant by FFR and deferred in non-significant stenoses (group II).
      Overall, coronary angioplasty was performed in 71 vessels (41%) and deferred in
      100 (59%). Cumulative cardiac events occurred in 12.9% of group I patients and in
      24.1% of group II patients (chi-squared = 1.57, P = 0.20). TVR was required in 5%
      of the stenoses untreated based on FFR result in both groups and in 12.6% of
      stenoses that underwent coronary angioplasty (chi-squared = 3.25, P = 0.07;
      relative risk = 2.5, 95% confidence interval = 0.88-8.61). CONCLUSIONS: In
      patients with angiographically intermediate stenoses, functional evaluation by
      FFR to select lesions that do not need to be treated invasively is safe.
      Unnecessary angioplasty and stenting may be saved in more than one half of
      individual coronary stenoses. The risk of major cardiac events and TVR of
      functionally non-significant stenoses is lower than the risk associated with
      coronary angioplasty. Our observations further support the use of pressure wire
      for physiological assessment of coronary artery stenosis in the catheterization
      room.

PMID- 16645382
TI  - Transcatheter closure of complex atrial septal defects: feasibility and mid-term
      results.
AB  - OBJECTIVE: Transcatheter closure of atrial septal defects (ASDs) is currently a
      reliable alternative to surgery, even though challenging in the case of complex
      septal anatomy. The aim of this study was to evaluate the feasibility and mid
      term results of percutaneous closure of complex ASDs in a tertiary referral
      centre compared with simple ASD closure. METHODS: Between April 2000 and November
      2004, 209 patients were submitted to transcatheter ASD closure; 83 patients
      (39.7%) presented with a complex defect (large ASDs with a deficient rim or a
      multifenestrated/aneurysmal septum) and were treated using different devices
      tailored to the atrial septal anatomy. RESULTS: The transcatheter procedure was
      successful in 72 patients (86.8%), using a single device in 69 patients and two
      devices in the remaining three patients. Overall, 71 Amplatzer septal occluders,
      two multifenestrated Amplatzer septal occluders and two Cardioseal/Starflex
      devices were used. Procedural and fluoroscopy times were 141 +/- 45 min and 28 +/
      22 min, respectively (P < 0.0001 vs. simple ASD closure for both comparisons).
      Procedure-related complications were recorded in nine patients (12.5%) (P < 0.01
      vs. simple ASD closure). One patient required surgical repair of a femoral
      arteriovenous fistula and another developed mitral valve dysfunction. Immediate
      ASD occlusion was recorded in 59.7% of patients, reaching 95.9% at the last
      follow-up control (P = NS vs. simple ASD closure for both comparisons).
      CONCLUSIONS: Percutaneous closure of complex ASDs may be considered technically
      feasible, relatively safe and highly effective, although the procedure is still
      significantly more demanding than transcatheter closure of simple ASDs.

PMID- 16645383
TI  - Usefulness of cardiac calcification on two-dimensional echocardiography for
      distinguishing ischaemic from nonischaemic dilated cardiomyopathy: a preliminary
      report.
AB  - BACKGROUND: Aortic valve calcification (AVC) and/or mitral annulus calcification
      (MAC) is considered to be a marker of atherosclerosis and has been demonstrated
      to predict cardiovascular morbidity and mortality. AIM: We hypothesized that the
      presence of cardiac calcification by echocardiography can be used in the
      differential diagnosis between ischaemic (DCMI+) and nonischaemic dilated
      cardiomyopathy (DCMI-). METHODS: We evaluated 62 patients with DCM (38 males,
      mean age 66 +/- 10 years, LVEF < 40%), without any prior history of myocardial
      infarction or coronary intervention, who were undergoing coronary angiography for
      aetiological diagnosis. DCMI+ was considered present when a > or = 70% stenosis
      of at least one coronary artery was found. AVC, MAC, aortic wall and papillary
      muscle calcifications were semiquantitatively assessed by two-dimensional
      echocardiographic examination with a calcium score ranging from 0 (no
      calcifications) to 8 (calcium in all four sites). RESULTS: DCMI+ was found in 20
      out of 62 patients. As expected, there were no differences in LVEF and LV end
      diastolic diameters between DCMI+ and DCMI--patients (29 +/- 8% versus 31 +/- 10%
      and 66 +/- 6 versus 68 +/- 8 mm, respectively; not significant). Regional wall
      motion abnormalities and conventional risk factors for atherosclerosis, such as
      hypertension and hypercholesterolaemia, were significantly more frequent in the
      DCMI+ compared to the DCMI- group. On the other hand, the calcium echo score was
      4.6 +/- 2 (range 1.7-7.3) in DCMI+ patients and 0.8 +/- 0.95 (range 0-4) in DCMI-
      patients (P < 0.05). A calcium score > or = 3 was observed in 18 out of 20 (90%)
      DCMI+ patients and only in three of 42 (8%) DCMI--patients. CONCLUSIONS: The
      assessment of cardiac calcification by two-dimensional echocardiography could
      represent a simple, noninvasive and inexpensive approach to assess the aetiology
      (ischaemic versus nonischaemic) of dilated cardiomyopathy.

PMID- 16645384
TI  - The role of cardiac calcification detected by echocardiography in diagnosis of
      ischaemic dilated cardiomyopathy.

PMID- 16645385
TI  - Distribution of potential cardiac sources of embolism in young and older stroke
      patients: implications for recurrent vascular events.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) has improved the diagnostic
      evaluation of ischemic stroke patients, permitting detection of potential cardiac
      sources of embolism. The present study aimed to evaluate the distribution of
      potential cardioembolic sources in young versus older stroke patients and their
      clinical implication for recurrent vascular events. Two hundred and twenty-eight
      patients with undetermined ischemic stroke were enrolled in the study. METHODS:
      All patients were submitted to transthoracic and to TEE examination. The mean
      follow-up period was 43 +/- 19 months. RESULTS: The overall detection of cardiac
      sources of embolism was significantly higher in younger than in older patients (P
      = 0.006). Atrial septal abnormalities were more prevalent in the younger than in
      the older population (P = 0.006), whereas complicated aortic plaques were
      detected more often in older patients. During the follow-up period of 4-5 years,
      we identified 40 recurrent stroke episodes or vascular deaths. As expected, there
      was a significant difference in recurrent vascular events and death of older
      patients compared to the younger ones (P = 0.025). CONCLUSIONS: The present study
      demonstrates that atrial septal abnormalities and aortic atheromas are the most
      prevalent echocardiographic findings in young and elderly stroke patients,
      respectively. Complicated aortic atheroma is strictly correlated with recurrent
      cerebral vascular events or death.

PMID- 16645386
TI  - Early mobilization after pacemaker implantation.
AB  - BACKGROUND: There are no international guidelines indicating how long a patient
      should stay strictly in bed after pacemaker implantation. In the present study,
      we tested a new protocol concerning the mobilization of patients 3 h after
      receiving a single or a dual-chamber pacemaker. METHODS: Consecutive patients who
      underwent single or dual-chamber pacemaker implantation were randomized to a 3 or
      24 h immobilization protocol. Only bipolar passive fixation leads were computed.
      After the implant, an elastic bandage was put on the homolateral shoulder of all
      patients for 24 h. A complete clinical and electronic follow-up was performed
      before discharge and repeated 2 months later. End-points considered were the
      displacement of the lead, high pacing thresholds (> 3.5 V/0.4 ms at the discharge
      or > 2.5 V/0.4 ms at the 2-month follow-up), sensing defects not corrigible by
      programming and clinical complications of the pocket RESULTS: One hundred and
      thirty-four patients were included in the study: 57 in group A (mobilization
      after 3 h) and 77 in group B (24 h). In group A, one haematoma and two
      displacements occurred in three patients. In group B, we registered one
      haematoma, one subclavian vein thrombosis, three displacements and three high
      stimulation thresholds. No statistical differences were observed between the end
      points of group A versus B. CONCLUSIONS: The present study shows that an early
      mobilization protocol is feasible because no statistical differences resulted
      from the two groups of study as regards clinical outcome, complications and
      electronic measurements of the implanted devices, which have been followed up for
      2 months.

PMID- 16645387
TI  - A computer protocol to evaluate subjects with chest pain in the emergency
      department: a multicenter study.
AB  - OBJECTIVE: Chest pain is a frequent cause of medical admission to the emergency
      department and the main differential diagnosis is between coronary and non
      coronary chest pain. We elaborated a computer protocol for the management of
      patients with chest pain. METHODS: The computer protocol was made of three
      sections according to clinical, electrocardiographic and biochemical data. Each
      section was coded by a letter indicating the probability of coronary chest pain
      for each section. The combination of the three letters formed a score string used
      to assign patients to four subgroups of overall probability of coronary chest
      pain (low, medium-low, medium-high, and high). Low-probability patients were
      discharged from the emergency department, whereas high-probability patients were
      admitted to the coronary care unit. The medium-probability patients underwent
      further evaluation by means of a stress test and were re-classified as having a
      final low probability (negative test) or high probability (positive test).
      RESULTS: We evaluated 472 patients (mean age 64 years, range 18-97 years; 47%
      female). The incidence of coronary events in patients with low, medium-low,
      medium-high and high overall probability was 1.9, 12.8,13.5 and 68.0%,
      respectively (P < 0.05). The positive and negative predictive values of the
      protocol were 64.7 and 97.1%, respectively. CONCLUSIONS: Our computer protocol
      represents a reliable method for the management of patients with chest pain and a
      non-diagnostic electrocardiogram.

PMID- 16645388
TI  - Video-assisted thoracoscopic clipping of patent ductus arteriosus: close to the
      gold standard and minimally invasive competitor of percutaneous techniques.
AB  - OBJECTIVE: To review our 12-year experience in video-assisted thoracoscopic
      surgery (VATS) for patent ductus arteriosus. METHODS: VATS was performed in 743
      patients. Three groups were compared: 24 low-birth-weight infants (LBWIs), 676
      children between 2.5-25 kg and 43 boys > 25 kg. A diameter of > 8 mm was the main
      contraindication. For 85 consecutive patients, hospital stay underwent cost
      analysis. RESULTS: Median age was 1.6 years (range 5 days-33 years) and median
      weight 9.0 kg (range 1.2-65 kg). Mortality was nil. Median operative time was 20
      min and hospital stay 2 days. Residual patency at discharge was 0% in LBWIs, 0.7%
      in children, and 4.7% in boys (P = NS) and 0, 0.3, and 4.7% at follow-up (P =
      0.001). Persistent recurrent laryngeal nerve dysfunction was recorded in 4.2% of
      LBWIs, 0.3% of children and 0% of boys (P = 0.012). Total mean cost was Euro 5954
      +/- 2110. CONCLUSIONS: The success rate of VATS clipping compares favorably with
      the thoracotomic approach but without chest wall trauma and it may have a very
      favorable cost-effective therapeutic balance compared to transcatheter
      techniques.

PMID- 16645389
TI  - D-dimer serum levels in a case of type B aortic dissection. A rapid test for the
      early diagnosis of acute aortic disease?
AB  - This article reports on a case of acute type B aortic dissection presenting with
      electrocardiographic abnormalities mimicking an acute coronary syndrome,
      associated with high D-dimer levels in the acute phase and normalization in the
      chronic phase of the disease process. This case report is consistent with recent
      data from the literature suggesting that D-dimer levels might be a useful
      biochemical tool in the diagnostic work-up of patients with suspected acute
      aortic dissection.

PMID- 16645390
TI  - An unusual case of cardiac tamponade.
AB  - A case of a 67-year-old woman with cardiac tamponade caused by toothpick
      ingestion is presented. At clinical presentation, it mimicked postinfarction
      ventricular free wall rupture and the diagnosis was not made until the operation.
      Ingested toothpicks have often been reported as a cause of intestinal injuries,
      but in this rare case the toothpick migrated into the pericardium and caused
      laceration of the right coronary artery.

PMID- 16645391
TI  - An uncommon cause of acute pericardial disease. The changing aetiology of
      traumatic pericardial disease.

PMID- 16645392
TI  - Aortic intramural hematoma: a case report of spontaneous resolution.
AB  - Aortic intramural hematoma is an acute aortic syndrome caused by hemorrhage
      within the aortic wall and characterized by the absence of an intimal tear and
      false lumen, which are the main features of classic aortic dissection. Although
      surgical intervention represents the standard management of type A aortic
      intramural hematoma, the possibility of treating some patients with medical
      therapy associated with serial imaging evaluations at follow-up has recently been
      demonstrated.

PMID- 16645393
TI  - Introduction.

PMID- 16645394
TI  - Does sports activity enhance the risk of sudden cardiac death?
AB  - Vigorous physical exercise may precipitate acute fatalities in both adults and
      young competitive athletes with concealed heart diseases. However, the risk
      benefit ratio of physical exercise differs among these two age groups. In adults,
      physical activity can be regarded as a 'double-edged sword': vigorous exertion
      increases the incidence of acute coronary events in individuals who did not
      exercise regularly, whereas habitual physical activity reduces the overall risk
      of myocardial infarction and sudden coronary death by preventing development and
      progression of atherosclerotic coronary artery disease. On the other hand, in
      adolescents and young adults sports activity is associated with a significant
      increase of the risk of sudden death. Sport is not per se the cause of the
      enhanced mortality in this age group; rather, it acts as a trigger of cardiac
      arrest in those athletes who are affected by silent cardiovascular conditions,
      mainly cardiomyopathy, premature coronary artery disease and congenital coronary
      anomalies, which predispose to life-threatening ventricular arrhythmias during
      physical exercise.

PMID- 16645395
TI  - Can a child who has been operated on for congenital heart disease participate in
      sport and in which kind of sport?
AB  - Exercise training and sports participation is an important part of the physical,
      psychological and metabolic growth of any child and adolescent, and this is also
      true for patients with congenital heart disease (CHD). As one can expect,
      exercise tolerance varies widely according to the CHD and to the treatment
      received, but the functional result achieved in the single patient is more
      important. Individual counselling is necessary and should be based on
      observations/results of thorough cardiovascular assessment. Exercise testing is
      the ideal tool to identify patients in whom exercise may induce arrhythmias or
      haemodynamic instability. In general, some degree of aerobic, isometric exercise
      training can be granted to most patients operated on for CHD. Serial evaluations
      may be required because of changing haemodynamic and functional status with time.

PMID- 16645396
TI  - Brugada-like electrocardiogram pattern: how to stratify the risk for sudden
      cardiac death. Is sports activity contraindicated?
AB  - Brugada syndrome is associated with a considerable risk of sudden death in young
      and otherwise healthy adults. The syndrome is estimated to be responsible for at
      least 4% of all sudden deaths and at least 20% of sudden deaths in patients with
      structurally normal hearts. The diagnosis of Brugada syndrome is based on
      peculiar electrocardiogram (ECG) abnormalities classified by the European Society
      of Cardiology in three types: type 1 (coved-type) is the diagnostic pattern; type
      2 (saddle-back type); and type 3 are considered significant if there is a
      conversion to a type 1, spontaneously or during administration of class I A/C
      anti-arrhythmic drugs (flecainide, etc.). There is a general agreement about the
      high risk of sudden death in patients with previous cardiac arrest, for whom an
      implantable defibrillator (ICD) is recommended. In contrast, controversy exists
      on the correct clinical behaviour in individuals without a history of previous
      cardiac arrest. To stratify the risk in patients with type 1 pattern, three major
      factors have been suggested: typical ECG pattern in the basal state; a history of
      syncope; and inducible ventricular tachycardia/ventricular fibrillation during
      electrophysiological study (EPS). However, the indication and usefulness of an
      EPS is debatable. In patients with a type 2 or 3 pattern a pharmacological test
      is indicated in the presence of symptoms or of a familial history. With regard to
      sports eligibility, patients with a history of cardiac arrest should have an ICD
      and they can practise (low intensity) sport only after the implant of the device.
      Patients without documented cardiac arrest but at high risk (basal type 1 ECG
      pattern, syncope and/or positive EPS) should also have an ICD and they can
      practise (low intensity) sport only after the implant of the device. In patients
      at low risk (type 1 ECG pattern in the absence of symptoms, without family
      history and negative EPS) the behaviour regarding sport eligibility is not a
      matter of debate. In cases with type 2 or 3 pattern, in the absence of familial
      history and symptoms, a permissive behaviour should be assumed.

PMID- 16645397
TI  - Arrhythmogenic right ventricular cardiomyopathy is a life-threatening disease at
      high risk for cardiac arrest during effort. Minor forms are as dangerous as major
      forms?
AB  - The aim of the present study was the evaluation of physical activity likely to
      lead to the onset of life-threatening ventricular arrhythmias in subjects
      affected by arrhythmogenic right ventricular cardiomyopathy. In particular,
      strenuous physical activity can be dangerous in patients with minor or
      'concealed' forms of the disease, in whom no previous diagnosis has been made. In
      these patients preventive strategies cannot be adopted due to the lack of a
      clinical diagnosis, and so physical effort can be responsible for the first
      noticeable symptom of the disease.

PMID- 16645398
TI  - Long QT syndrome and short QT syndrome: how to make correct diagnosis and what
      about eligibility for sports activity.
AB  - Cardiologists are involved in evaluating the eligibility of athletes to practise
      competitive sport and they should therefore be able to identify the
      electrocardiographic markers of long QT syndrome (LQTS) and short QT syndrome
      (SQTS). An overview of the clinical criteria to perform measurement of QT
      interval on 12-lead electrocardiogram is provided herein and several instances in
      which the diagnosis of either LQTS or SQTS may leave the clinician uncertain are
      discussed. A critical appraisal of current recommendations for eligibility to
      competitive sport is also provided as well as some of the authors' personal
      opinions on the practice of recreational activities in patients with abnormal
      repolarization.

PMID- 16645399
TI  - The athlete's heart and hypertrophic cardiomyopathy: two conditions which may be
      misdiagnosed and coexistent. Which parameters should be analysed to distinguish
      one disease from the other?
AB  - According to the statements from the International Cardiological Committees on
      Eligibility for Sports, athletes with a clinical diagnosis of hypertrophic
      cardiomyopathy (HCM) should be excluded from most competitive sports, with the
      possible exception of those of low intensity. Clinical distinctions between
      physiological athlete's heart and pathological conditions such as HCM have
      critical implications especially for trained athletes. Even if the standard two
      dimensional echocardiography represents an irreplaceable method in the evaluation
      of cardiac adaptations to physical exercise, the data currently available suggest
      the usefulness of Doppler myocardial imaging (DMI) in the assessment of the
      myocardial systolic and diastolic function of the athlete's heart. On this
      ground, the combined use of standard two-dimensional echocardiography and DMI may
      be taken into account for a valid, non-invasive and easily repeatable evaluation
      of both physiological and pathological ventricular hypertrophy, and in selecting
      a subgroup of HCM patients at higher risk of cardiac events. In particular, DMI
      analysis in the trained individual has demonstrated an interesting opportunity
      for: (1) the differential diagnosis from pathological left ventricular
      hypertrophy due to HCM; (2) the prediction of cardiac performance during physical
      effort; (3) the evaluation of bi-ventricular interaction; (4) the analysis of
      myocardial adaptations to various training protocols; and (5) the early
      identification of specific genotypes associated with cardiomyopathies.

PMID- 16645400
TI  - The genetics of left ventricular remodeling in competitive athletes.
AB  - Left ventricular (LV) remodeling in competitive athletes is a complex phenomenon,
      in which genetic and environmental determinants are implicated. In recent years,
      several investigations have demonstrated an association between LV remodeling and
      the angiotensin-converting enzyme (ACE I/D) and/or angiotensinogen (AGT M/T)
      polymorphism, with athletes with the DD and/or TT alleles, respectively, showing
      the greatest increase in LV mass, independent from other determinants. However,
      the impact of the known genetic determinants on LV remodeling is at present
      incomplete, and comparative assessment of the genetic and environmental factors,
      such as the type and intensity of athletic conditioning, suggests that genetic
      determinants may explain up to one-quarter of the overall variability of LV
      dimensions. A better understanding of genetic factors may provide an insight into
      the pathways producing physiological cardiac remodeling, and will be important in
      understanding the intrinsic nature and clinical significance of the extreme LV
      morphologic changes observed in highly trained and elite athletes.

PMID- 16645401
TI  - The Wolff-Parkinson-White electrocardiogram pattern in athletes: how and when to
      evaluate the risk for dangerous arrhythmias. The opinion of the paediatric
      cardiologist.
AB  - Although diagnostic assessment and treatment have been described in detail in
      patients with symptomatic Wolff-Parkinson-White (WPW) syndrome, the management of
      asymptomatic subjects remains controversial. Usually they are assumed to have a
      benign prognosis, although they do very occasionally present with ventricular
      fibrillation (VF) as the first manifestation of the syndrome. Discovering a WPW
      pattern in a previously asymptomatic athlete on a routine electrocardiogram (ECG)
      identifies the necessity for more accurate screening tests. However, non-invasive
      methods (Holter monitoring, exercise treadmill testing) seem to be relatively
      incomplete for risk stratification, especially for athletes. Current guidelines
      do not always recommend a routine electrophysiological study (EPS) in patients
      with an asymptomatic WPW ECG pattern, especially in children younger than 12
      years. Individuals who engage in high-risk occupations or those patients who have
      a pre-excitation pattern which precludes them from following their chosen career
      or activities may be exceptions. The presence of inducible reciprocating
      tachycardia during EPS, especially when it triggers atrial fibrillation with
      short RR interval, can represent a specific risk marker of dangerous arrhythmias.

PMID- 16645402
TI  - Idiopathic ventricular arrhythmias in athletes: their causes and when to grant
      sports eligibility.
AB  - The clinical assessment of ventricular tachyarrhythmias in trained athletes is of
      particular significance because of the recognition that young and otherwise
      healthy athletes may have unsuspected and potentially lethal cardiovascular
      disease, which can result in sudden arrhythmic death. Therefore, the risk
      associated with competitive sports and training in athletes with ventricular
      tachyarrhythmias is still not completely resolved. Ventricular arrhythmias are
      common in trained athletes and are usually not associated with underlying
      cardiovascular abnormalities. Recent studies have shown that such arrhythmias (in
      the absence of heart disease) do not convey adverse clinical significance and
      probably do not per se justify disqualification from competitive sports.

PMID- 16645403
TI  - Bicuspid aortic valve: an innocent finding or a potentially life-threatening
      anomaly whose complications may be elicited by sports activity?
AB  - The bicuspid aortic valve is the most frequent congenital anomaly of the heart in
      adults. Since the 1970s, with the advent of two-dimensional echocardiography, the
      in-vivo diagnosis of bicuspid aortic valve has become easier and greater
      attention has been paid to this anomaly in normal young people, particularly in
      sportsmen because, from a theoretical point of view, physical exercise may stress
      the abnormal aortic valve, favouring an early deterioration of the valve itself,
      as well as a dilation of the ascending aorta. Although the bicuspid aortic valve
      may remain without clinical consequences for a lifetime, it may be responsible
      for severe complications such as aortic stenosis, aortic insufficiency,
      endocarditis and aortic dilation/dissection, sometimes requiring surgery.
      Moreover, the bicuspid aortic valve may be associated with other cardiovascular
      anomalies, mainly aortic coarctation. At present there are no prospective studies
      dealing with effect of physical training and competitive sports on the natural
      course of the bicuspid aortic valve. However, in order to take any decision about
      sports eligibility, sports physicians should perform an initial accurate staging
      of the bicuspid aortic valve, taking into account haemodynamic factors, aortic
      complications and associated significant cardiovascular anomalies. A strict
      follow-up, with serial cardiological controls, is mandatory as well as antibiotic
      prophylaxis for endocarditis, particularly in subjects engaged in contact sports.

PMID- 16645404
TI  - Should sports activity be encouraged or contraindicated in hypertensive subjects?
AB  - Hypertension is considered one of the major risk factors for cardiovascular
      disease. There are a number of different approaches to the prevention, control
      and treatment of hypertension. One of these provides lifestyle modification as a
      means to facilitate drug step-down or drug withdrawal in hypertensive patients
      subjected to a pharmacological treatment, but also as a means to control blood
      pressure and reduce the risk of developing hypertension in subjects that have
      abnormal blood pressure but are not candidates for drug therapy. Lifestyle
      modification includes physical activity, and there is an ever-increasing amount
      of evidence that physical activity can modify the history of hypertension, acting
      as a reducer either of blood pressure or of the other cardiovascular risk
      factors. The aim of this article was to analyse the effects of exercise on blood
      pressure (neuro-hormonal, hormonal and vessel effects), illustrate which are the
      influences of age and gender on exercise-induced reduction of blood pressure,
      indicate how much exercise (in terms of intensity, frequency and duration) is
      required to induce positive modification of blood pressure and evaluate current
      Italian criteria for sports ability in athletes with hypertension.

PMID- 16645405
TI  - What to suggest after coronary angioplasty or bypass surgery procedures: a
      sedentary lifestyle, moderate physical activity or sports activity?
AB  - Patients undergoing coronary percutaneous revascularization are usually sedentary
      individuals. It is well known that physical activity has central and peripheral
      benefit in subjects with or without coronary heart disease. The physiological
      principles of physical activity, which are essential during rehabilitation
      activity, have led to an evolution in the concept of sports therapy with a
      preventive and therapeutic efficacy even in groups of moderately advanced age.
      The training effect must be adequate in the ischaemic patient during baseline
      conditions with increased intra-ventricular pressure regimens and with
      arrhythmological potential. Metabolic, muscular and general adaptation in the
      ischaemic patient is essential for improved economy of effort. It is necessary to
      stratify patients to identify low to moderate risk in order to prepare training
      programmes and eventually sports activity. Sports activity and training programme
      selection must be performed by a cardiologist who understands the problemmes and
      potentials of physical training that can be performed even in a gym.

PMID- 16645406
TI  - Myocarditis: when to suspect and how to diagnose it in athletes.
AB  - Myocarditis should be suspected in athletes with unexplained cardiac arrhythmias
      and dysfunction, especially if preceded by a flu-like syndrome. An early
      diagnosis is desirable in order to avoid the risk of fatal consequences, since
      physical activity can enhance the inflammatory process. Although several
      diagnostic tools can be useful for the diagnosis of myocarditis, endomyocardial
      biopsy is still the gold standard. Athletes with myocarditis should be withdrawn
      from all competitive sports for at least 6 months and resume training when
      ventricular function and cardiac dimensions return to normal and the clinically
      relevant arrhythmias disappear. In the presence of life-threatening arrhythmias
      or rapidly progressive cardiac dysfunction an antiviral or an immunosuppressive
      treatment should be considered depending on whether a viral agent is present or
      absent, respectively, in the myocardium.

PMID- 16645407
TI  - Plasma levels of metalloproteinases-9 and -2 in the acute and subacute phases of
      type A and type B aortic dissection.
AB  - OBJECTIVES: Aortic dissection is characterized by an acute phase of medial
      dissection and a subacute-chronic phase of vessel wall repair. Matrix
      metalloproteinases (MMPs), through degradation of extracellular matrix, may play
      an important role in these processes. Elevation of MMPs might represent an
      opportunity to diagnostically characterize acute or chronic aortic processes. We
      examined the potential diagnostic role of MMP-9 and MMP-2 in different phases of
      aortic dissection. METHODS: Plasma levels of MMPs were evaluated by enzyme-linked
      immunosorbent assay technique in 13 patients affected by acute aortic dissection
      (nine type A, four type B). Ten healthy subjects were used as controls. In
      patients with type B aortic dissection treated medically, plasma curves (1, 3, 6,
      12, 24, 48 and 96 h; 1 and 2 weeks; and 2 months from symptom onset) were also
      assessed. Aortic tissue samples obtained during surgery were evaluated by
      immunohistochemistry and western blot for MM-9 and tissue inhibitor of
      metalloproteinase-1 expression. RESULTS: MMP-9 plasma levels were increased in
      patients affected by type A and type B aortic dissection presenting within 1 h
      from onset of symptoms compared to controls (29.3 +/- 16.1 and 16.7 +/- 2.1 ng/ml
      versus 7.74 +/- 1.6 ng/ml, P < 0.03, respectively). No differences were detected
      in MMP-2 plasma levels compared to controls (4.84 +/- 1.2 ng/ml for type A and
      6.16 +/- 0.6 ng/ml versus 3.17 +/- 1.0 ng/ml for controls, P = NS, respectively).
      In type B aortic dissection, mean MMP-9 plasma levels increased significantly
      from hospital admission to 2-month follow-up (16.7 +/- 2.1 ng/ml versus 58.0 +/-
      8.2 ng/ml, P < 0.0001). Conversely, no difference in MMP-2 plasma levels was
      evident during follow-up (6.16 +/- 0.6 ng/ml versus 4.28 +/- 0.4 ng/ml, P = NS,
      respectively). Low-moderate (+/++) expression of MMP-9 was evident at
      immunohistochemistry in the acute phase whereas a marked expression (++++) was
      detected in the subacute phase. CONCLUSIONS: This pilot study suggests that the
      acute and subacute phase of both type A and type B aortic dissection is
      characterized by an increase of MMP-9 plasma levels. A marked increase is also
      evident in the subacute phase of medically treated type B aortic dissection as an
      expression of aortic wall remodelling. An increase of proteolytic activity could
      accompany attempts of the dissected aorta to heal itself but such a phenomena
      might further weaken the aortic wall, predisposing it to dilation and/or rupture.

PMID- 16645408
TI  - Alpha- and beta-adrenergic receptor polymorphisms in hypertensive and
      normotensive offspring.
AB  - BACKGROUND: The offspring of hypertensive families are characterized by higher
      arterial blood pressure values and a depressed autonomic control of heart rate.
      The present study aimed to verify whether these differences are associated with a
      different genotype distribution of functionally relevant polymorphisms of the
      alpha- and beta-adrenergic receptor (AR) genes. METHODS: We selected 109 age- and
      sex-matched young normotensive subjects with (FH+, n = 56) and without (FH-, n =
      53) a family history of hypertension who underwent evaluation of arterial
      pressure; 24-h electrocardiogram monitoring to assess time-domain parameters of
      autonomic heart rate control [i.e. mean RR interval (NN), SD of RR intervals
      (SDNN) and mean square root of the differences of consecutive RR intervals
      (rMSSD)]; spectral baroreflex sensitivity measurement; and echo-Doppler to assess
      diastolic function and left ventricular mass. They were also characterized for
      the following polymorphisms by means of polymerase chain reaction-restriction
      fragment polymorphism analysis: Arg492Cys in the alpha1a-AR; Del301-303 in the
      alpha2b-AR; Ser49Gly and Arg389Gly in the beta1-AR; and the 5' leader cistron
      Arg19Cys, Arg16Gly and Gln27Glu in the beta2-AR. RESULTS: FH+ individuals showed
      a higher systolic pressure, a lower SDNN and a greater isovolumic relaxation time
      compared to normotensive offspring. No differences were found between the two
      groups when genotype distribution of the studied polymorphisms was considered.
      Subjects carrying alpha1a-AR Cys492 allelic variant showed lower values of NN,
      SDNN and rMSSD, independent of age, gender and body mass index. CONCLUSIONS: The
      functionally relevant polymorphisms of alpha2b-, beta1- and beta2-AR genes are
      not associated with a family history of essential hypertension. The Arg492Cys
      polymorphism of the alpha1a-AR gene, although not associated with a family
      history of hypertension, was strongly related to autonomic control of heart rate.

PMID- 16645409
TI  - Slow coronary flow and stress myocardial perfusion imaging. Different patterns in
      acute patients.
AB  - OBJECTIVE: We investigated myocardial perfusion in acute patients with slow
      coronary flow (SCF) at angiography. Whether impaired myocardial perfusion occurs
      in acute patients with SCF is unknown. METHODS: We enrolled 28 consecutive
      patients with SCF in the epicardial coronary arteries with no evidence of
      significant stenosis. SCF affected a single coronary artery in 14 patients (group
      A) and all three coronary vessels in 14 others (group B). Coronary angiography
      was repeated after dipyridamole infusion and single photon emission computed
      tomography was performed using dipyridamole as the stress agent. The Thrombolysis
      in Myocardial Infarction frame count was measured in SCF vessels at baseline and
      after dipyridamole infusion. RESULTS: Mean Thrombolysis in Myocardial Infarction
      frame count significantly decreased after dipyridamole in both groups. At
      baseline, mean values of the single photon emission computed tomography score
      were 31.5 +/- 1.6 and 25.1 +/- 2.1 in groups A and B, respectively. After
      dipyridamole, they increased from 31.5 +/- 1.6 to 37.8 +/- 1.4 (P < 0.001) in
      group A, whereas a further decrease to 15.0 +/- 1.2 (P < 0.005) was observed in
      group B. CONCLUSIONS: An opposite behavior of myocardial perfusion was observed
      after dipyridamole infusion: a normal response in patients with SCF affecting one
      single coronary artery versus an ischemic-like response in those with CSF
      affecting all three coronary arteries.

PMID- 16645410
TI  - Comparison between four-slice computed tomography and coronary angiography for
      the assessment of coronary stents.
AB  - BACKGROUND: The present study aimed to evaluate the diagnostic accuracy of four
      slice computed tomography for the detection, localization and patency assessment
      of metal coronary stents in a general population referred for coronary
      angiography late after coronary angioplasty. METHODS: Twenty-four consecutive
      patients with 34 coronary stents underwent multislice computed tomography within
      24 h before a clinically driven coronary angiography performed 245 +/- 92 days
      after coronary stent implantation. For each patient, two independent operators
      were asked to evaluate the overall number of stents, the treated coronary vessels
      and segments, the presence of side-branches in the stented segment, the vessel
      patency, and the presence of binary in-stent restenosis. RESULTS: Four-slice
      computed tomography was feasible in 23 out of 24 patients (96%). Diagnostic
      accuracy was 94% for stent detection, 96% for the recognition of the stented
      coronary vessel and 97% for the identification of the stented segment. Accuracy
      in detection of side-branches in the stented segment, vessel patency and in-stent
      restenosis was 86%, 88% and 50%, respectively. CONCLUSIONS: Four-slice computed
      tomography is accurate in the identification of the stented coronary vessel and
      segment. By contrast, accuracy is low in the detection of vessel patency and in
      stent restenosis. Such a technique does not appear to be useful as a screening
      tool before invasive diagnostic procedures.

PMID- 16645411
TI  - Enhanced external counterpulsation for treatment of refractory angina pectoris.
AB  - OBJECTIVE: Enhanced external counterpulsation (EECP) is a noninvasive, well
      tolerated treatment, effective for managing patients with refractory angina
      pectoris. The aim of this study was to evaluate the efficacy of EECP to relieve
      symptoms, to decrease myocardial ischaemia and to improve cardiac performance in
      patients with intractable angina, refractory to surgical and medical treatment.
      METHODS: Twenty-five patients (24 men and one woman, mean age 65 years) with
      persistent ischaemia notwithstanding optimal medical therapy or after
      interventional or surgical procedure, received EECP sessions for 35 h. Each
      patient underwent dobutamine stress echocardiography before and after treatment.
      We evaluated modifications in either cardiac systolic or diastolic function, and
      in wall motion score index. RESULTS: Eighty-four percent of patients showed an
      increase in at least one functional angina class. We did not observe any
      significant changes in fractional shortening and diastolic function. Thirty-six
      percent of patients had a reduction in the area of inducible ischaemia at
      dobutamine stress echocardiography after treatment. Unfortunately, because of the
      small sample size, we did not find any statistically significant difference.
      There was a trend showing that patients who benefited the most were those with
      the worst systolic function and with severely compromised segmental kinesis (P =
      NS). CONCLUSIONS: EECP is effective in relieving symptoms in patients with
      refractory angina and may reduce inducible ischaemia at dobutamine stress
      echocardiography, especially in patients with reduced systolic function and
      compromised segmental kinesis.

PMID- 16645412
TI  - Estimation of infarct size by single measurements of creatine kinase levels in
      patients with a first myocardial infarction.
AB  - OBJECTIVE: Enzymatic estimation of infarct size is desirable in the reperfusion
      era, because a possible discrepancy with the observed asynergic area of the left
      ventricle may suggest the presence of stunned myocardium. Unfortunately, timely
      myocardial reperfusion produces a rapid washout of creatine kinase (CK) in blood
      flow, which overestimates infarct size. In this perspective, we investigated
      whether the mid-terminal portion of the CK time-activity curve could predict
      infarct size more reliably. METHODS: Enzymatic infarct size was calculated by
      peak CK levels, the CK area under the curve and by single CK values, in 103
      patients with a first ST-elevation myocardial infarction, and compared to the
      left ventricular akinetic area. The wall motion asynergy score at follow-up was
      considered as the actual infarct size. RESULTS: In patients with peak CK within
      10 h of symptom onset, CK levels at 30 h showed a high independent correlation (r
      = 0.83; P < 0.001) with infarct size. In patients with late peak CK (> 10 h), CK
      levels at 12 h turned out to be the best predictor of infarct size (r = 0.55; P <
      0.01). At multivariate regression analysis, peak CK was the best predictor of
      infarct size in the whole population (r = 0.61; P < 0.001). CONCLUSIONS: In
      patients with ST-elevation myocardial infarction and early peak CK, infarct size
      at follow-up could be better estimated with single values of the mid-terminal
      portion of the CK time-activity curve.

PMID- 16645413
TI  - Vitamin E increases the risk of developing heart failure after myocardial
      infarction: Results from the GISSI-Prevenzione trial.
AB  - OBJECTIVE: Although results from basic science suggested a protective role of
      vitamin E treatment in the prevention of cardiovascular disease, recent evidence
      indicates increased cardiovascular mortality due to vitamin E treatment.
      Recently, the HOPE trial showed an increment of the incidence of congestive heart
      failure (CHF) in patients treated with vitamin E. METHODS: We explored the effect
      of vitamin E on development of CHF in 8415 postinfarction patients without CHF at
      baseline, with an echocardiographic measure of left ventricular ejection
      fraction, who have been followed up for 3.5 years in the GISSI-Prevenzione trial.
      CHF during follow-up was defined as hospitalization or death for CHF. Cox
      regression models adjusted for relevant prognostic indicators were fitted.
      RESULTS: Main clinical characteristics were balanced in the 4202 and 4213
      patients allocated vitamin E and control group, respectively. During follow-up,
      220 patients (2.6%) developed CHF. Patients allocated vitamin E had a
      nonsignificant 20% (95% confidence intervals 0.92-1.56, P = 0.18) increased risk
      of developing CHF. Vitamin E treatment, however, was associated with a
      significant 50% increase (95% confidence intervals 1.03-2.20, P = 0.034) of CHF
      in patients with left ventricular dysfunction (ejection fraction < 50%).
      CONCLUSIONS: Our results confirm and extend previous evidence on the possible
      harmful effect of vitamin E on ventricular function in patients with
      cardiovascular disease. Available evidence should discourage the use of vitamin E
      in patients with left ventricular dysfunction.

PMID- 16645414
TI  - Effect of the increase in valve area after aortic valve replacement with a 19-mm
      aortic valve prosthesis on left ventricular mass regression in patients with pure
      aortic stenosis.
AB  - OBJECTIVES: Although patients with aortic stenosis, who receive 19-mm valves, are
      at high risk for prosthesis-patient mismatch, most of them show a significant
      left ventricular mass (LVM) regression postoperatively. The aim of this study was
      to identify factors predicting postoperative relative LVM regression in this
      subgroup of patients. METHODS: A population of 44 patients operated on for pure
      aortic stenosis and receiving a 19-mm valve was studied by echocardiography at
      1.4 +/- 0.5 years postoperatively. RESULTS: The mean relative LVM regression was 
      19.3 +/- 18.9%, the mean gradient drop was -31.6 +/- 13.3 mmHg, and the mean
      Delta increase in aortic area index (postoperative aortic area index minus
      preoperative aortic area index) was 0.30 +/- 0.14 cm/m. Thirty-two patients had
      an indexed effective orifice area of less than 0.8 cm/m. At multivariate analysis
      (r = 0.63; r = 40%; P < 0.0001) preoperative LVM (P = 0.006), hypertension (P =
      0.018) and Delta aortic area index (P = 0.049) were independent predictors of
      relative LVM regression. CONCLUSIONS: Our study shows that, at least 1 year
      postoperatively, in patients receiving a 19-mm valve, LVM regression is
      influenced by several parameters, in particular preoperative LVM, hypertension
      and the magnitude of the increase in aortic area.

PMID- 16645415
TI  - Late cure after radiofrequency catheter ablation in a pediatric patient.
AB  - A 12-year-old female with the Wolff-Parkinson-White syndrome underwent an
      electrophysiologic study followed by radiofrequency catheter ablation of the left
      lateral accessory pathway. After several unsuccessful attempts, the procedure was
      stopped because of early recurrence of accessory pathway conduction. Twenty-four
      hours after the procedure, the patient was found without ventricular pre
      excitation pattern on the electrocardiogram. During a 12-month follow-up, the
      Wolff-Parkinson-White pattern was no longer present. A transesophageal
      electrophysiologic study showed no further tachycardia induction and the patient
      is still asymptomatic. This report raises the issue that ablation-induced lesions
      may evolve considerably during the first few days after ablation, leading to
      either recurrent accessory pathway conduction or long-lasting complete cure.

PMID- 16645416
TI  - Aortic valve repair for papillary fibroelastoma.
AB  - We report the case of aortic valve-papillary fibroelastoma in a 66-year-old
      Belgian woman with a previous single episode of cerebral transient ischemic
      attack. Transthoracic two-dimensional echocardiography revealed a small mass
      adherent to the noncoronary cusp of the valve, which was confirmed by
      transesophageal echocardiography. Indication for surgery was performed because of
      a previous cerebral transient ischemic attack and for its potential risk of
      cerebral and coronary embolization. Surgical excision of the mass was performed
      with the need for glutaraldehyde-treated autologous pericardial patch repair of
      the aortic cusp. Intraoperative and postoperative transesophageal
      echocardiography both showed the valve to be competent. Postoperative recovery
      was uneventful. After a review of the literature, we conclude that, even if
      asymptomatic, and independent of their size, aortic valve papillary
      fibroelastomas justify surgical excision for their potential to systemic
      embolization. Moreover, we believe that a valve-sparing approach might be
      feasible with no recurrence after complete excision.

PMID- 16645417
TI  - Emergency repair of coronary perforation following percutaneous transluminal
      coronary angioplasty failure: A high-risk choice?
AB  - Coronary perforation is a recognized hazard following cardiac catheterization and
      may lead to a catastrophic outcome. Prompt decision-making following diagnosis is
      of key importance. Whether to perform prolonged attempts at percutaneous repair
      or to promptly refer the patient for emergency surgery soon after diagnosis still
      remains a matter of debate. We report the case of a 78-year-old woman suffering
      from coronary artery perforation during left anterior descending coronary artery
      percutaneous transluminal coronary angioplasty-stenting, who underwent
      unsuccessful multiple prolonged attempts at percutaneous repair followed by
      subsequent successful emergency surgery.

PMID- 16645418
TI  - Rotational atherectomy in the distal left anterior descending coronary artery
      through an internal mammary artery graft.
AB  - We report the case of a 53-year-old white man who began complaining of dyspnoea
      and angina 19 months after coronary artery bypass graft surgery. Coronary
      angiography revealed the presence of a long and critical stenosis in the native
      left anterior descending coronary artery, shortly after distal anastomosis of the
      left internal mammary artery. After failed predilatations with standard or
      cutting balloons, we successfully used the rotablator system, which allowed us to
      implant a bare-metal stent in the native left anterior descending coronary
      artery. However, stent deployment caused long linear graft dissection, which was
      reduced by drug-eluting stent implantation in the proximal and distal segments of
      the left internal mammary artery.

PMID- 16645419
TI  - Papillary fibroelastoma of the right atrium as an unusual source of recurrent
      pulmonary embolism.
AB  - Papillary fibroelastoma is the most common primary tumour of cardiac valves, with
      the potential for embolic events and obstructive effects. Location in non
      valvular endocardium is extremely rare. Transthoracic and transoesophageal
      echocardiography have greatly increased the ability to make the diagnosis of
      these surgically treatable tumours in a timely fashion. We report the case of a
      70-year-old woman with symptoms and ventilation-perfusion scan evidence of
      pulmonary embolization from a papillary fibroelastoma of the right atrium.
      Initial transthoracic echocardiography failed to identify the tumour, whereas
      transoesophageal echocardiography demonstrated a mobile echodense mass attached
      to the right atrial free wall. After surgical excision, histopathology revealed
      papillary fibroelastoma. The epidemiology, aetiology, localization, macroscopy,
      histopathology, immunohistochemistry, clinical presentation, diagnosis and
      management of cardiac papillary fibroelastoma are reviewed. The case is unusual
      with respect to the site of origin of the papillary fibroelastoma as well as its
      clinical presentation, which is clearly related to pulmonary embolization.

PMID- 16645420
TI  - Cardiovascular monitoring of HIV-infected patients.

PMID- 16645422
TI  - Pharmaceutical companies and medical therapeutics education.

PMID- 16645423
TI  - Impact of therapy initiation with amlodipine or losartan on hemodynamic endpoints
      and JNC-VI blood pressure stage.
AB  - The relative efficacy of long-acting calcium channel antagonists and angiotensin
      II receptor blocking agents has been described in clinical trials; however, their
      effectiveness in an actual practice setting has not been well studied. This study
      assessed the effectiveness of 2 commonly prescribed antihypertensives, amlodipine
      and losartan, either as monotherapy or as add-on for patients insufficiently
      controlled on beta-blocker or diuretic therapy. This was a retrospective,
      observational study that utilized electronic medical records. Hypertensive
      patients more than 40 years old who were new users of amlodipine or losartan were
      included in the study. Patients with congestive heart failure or those using
      antihypertensives other than diuretics or beta-blockers were excluded. Blood
      pressure (BP) readings were followed up to 6 months after enrollment. Univariate
      and multivariate regression models were used to assess the impact of amlodipine
      or losartan therapy on hemodynamic end points and on JNC-VI BP stage. A total of
      346 patients met the entry criteria. Of these, 275 (79.5%) amlodipine and 71
      (20.5%) were prescribed losartan. Mean changes in systolic and diastolic blood
      pressure were greater for patients receiving amlodipine in univariate and
      multivariate analyses (reduction of 20/8 and 11/4 mm Hg, respectively; P<0.05).
      Mean change in pulse pressure trended strongly in favor of amlodipine (11.8 mm Hg
      vs. 7 mm Hg, P = 0.08). Univariate analysis indicated that amlodipine-treated
      patients were more likely to move to a better JNC-VI BP stage, where as losartan
      treated patients, on average, moved to a worse stage. Amlodipine therapy was
      superior to losartan therapy among this population of hypertensive patients.

PMID- 16645424
TI  - Prevention of thiazide-induced hypokalemia without magnesium depletion by
      potassium-magnesium-citrate.
AB  - Thiazide can cause magnesium depletion, which may exaggerate renal potassium
      wasting and hypokalemia. The purpose of this double-blind, randomized trial was
      to compare the metabolic effects of potassium-magnesium-citrate (K-Mg-citrate)
      and potassium chloride (KCl) during long-term treatment with thiazide. Twenty-two
      normal volunteers received hydrochlorothiazide 50 mg/d. Ten subjects concurrently
      took K-Mg-citrate (42 mEq K/d and 21 mEq Mg/d), and 12 subjects were given KCl 42
      mEq/d. Serum potassium concentration remained unchanged during K-Mg-citrate
      supplementation, with a change from baseline of 21.7% over 6 months, compared
      with 26.4% with KCl supplementation. Serum electrolytes were normal and not
      significantly different between K-Mg-citrate and KCl. During K-Mg-citrate
      treatment, serum magnesium increased significantly by about 10%, associated with
      an adequate increase in urinary magnesium and a nonsignificant increase in
      monocyte and free muscle magnesium. Serum magnesium was unchanged, and monocyte
      and free muscle magnesium showed a nonsignificant decline during KCl
      supplementation. K-Mg-citrate provided an alkali load, increasing urinary pH, and
      reducing urinary undissociated uric acid. It also increased urinary citrate and
      tended to lower the saturation of calcium oxalate. KCl supplementation lacked
      these actions. K-Mg-citrate prevents thiazide-induced hypokalemia without
      provoking metabolic alkalosis. It seems to prevent magnesium depletion. By
      providing an alkali load, it retards the propensity for the crystallization of
      uric acid and probably of calcium oxalate. Though not conclusive, KCl
      supplementation may be less effective than K-Mg-citrate in maintaining
      normokalemia because of a subtle magnesium wasting. Moreover, KCl is devoid of
      protective action toward crystallization of stone-forming salts.

PMID- 16645425
TI  - Prevalence and causes of persistent use of hormone replacement therapy among
      postmenopausal women: a follow-up study.
AB  - In a previous study analyzing data from September 2002 to February 2003, we
      showed that, despite the Women's Health Initiative trial results, many women
      still remained on hormone replacement therapy (HRT) in an internal medicine
      practice. However, it is not known whether such use has persisted over time. We
      performed a retrospective chart analysis of 1000 postmenopausal women seen at the
      same internal medicine practice from January 2004 to May 2004 to establish
      whether the prevalence of HRT use had declined, remained stable, or increased
      when compared with our previous data and to determine the reasons for continued
      HRT use. Among 1000 postmenopausal women, mean age 66+/-9 years, 116 (12%)
      remained on HRT (HRT users) in 2004. The prevalence of HRT users declined from
      16% to 12% (P<0.01) over a period of 15 months. Among HRT users, the main reasons
      for continued use were severe menopausal symptoms in 39 (34%), patient preference
      in 17 (15%), osteoporosis or osteopenia in 14 (12%), failed attempt at
      discontinuation in 13 (11%), taper in progress in 12 (10%), gynecologist
      recommendation in 10 (9%), not documented in 8 (7%), and other reasons in 3 (3%).
      The use of HRT declined over time in an internal medicine clinic since the
      publication of the Women's Health Initiative study. However, 12% of the women
      still remained on HRT in 2004. The severity of menopausal symptoms, patient
      preference, and osteoporosis or osteopenia played a prominent role in the
      decision to remain on HRT.

PMID- 16645426
TI  - Valproic acid and risk of acute pancreatitis: a population-based case-control
      study.
AB  - To examine whether acute pancreatitis is associated with use of valproic acid.
      Through the population-based hospital discharge registries we identified all
      patients with an incident hospitalization of acute pancreatitis in the counties
      of North Jutland (data 1991 to 2003), Aarhus (data 1996 to 2003), and Viborg
      (data 1998 to 2003), Denmark. From the Danish Civil Registration System, we
      selected 10 sex-matched and age-matched population controls per case on the basis
      of risk set sampling. All prescriptions of valproic acid and other antiepileptic
      drugs within 90 days (present users) or 91 to 365 days (past users) before
      hospital admission with acute pancreatitis, or index date among controls, were
      collected from the prescription databases in the counties. We performed
      conditional logistic regression to estimate the relative risk of acute
      pancreatitis after exposure to valproic acid or other antiepileptic drugs,
      adjusting for gallstone diseases, alcohol-related diseases, hyperlipidemia, and
      hypercalcemia. We included 3083 cases of acute pancreatitis and 30,830 population
      controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of
      valproic acid was 1.9 [95% confidence interval (CI), 1.1-3.3); for past users,
      the adjusted OR was 2.6 (95% CI, 0.8-8.7). For users of other antiepileptic
      drugs, the corresponding adjusted ORs were 1.6 (95% CI, 1.2-2.2) and 1.8 (95% CI,
      1.1-3.0). Use of valproic acid is associated with an elevated relative risk
      estimate for acute pancreatitis, but it was not materially different from past
      use or use of other antiepileptic drugs. Therefore, our data challenge the
      hypothesis that valproic acid is an independent risk factor for acute
      pancreatitis.

PMID- 16645427
TI  - Management of anemic effects of chloramphenicol using amino acids on albino rats
      infected with Salmonella typhi.
AB  - Chloramphenicol is an antibiotic originally extracted from the fungus
      Streptomyces venezuelae, but it is now synthesized. It is a drug of choice for
      many of its toxicity in the blood-forming organs. The main objective of this
      study is to find out how to reduce the anemic effects of chloramphenicol and to
      increase its therapeutic efficacy using amino acid. In albino-rats infected with
      Salmonella typhi the results indicate that the rats became anemic after treatment
      with chloramphenicol. They also show that the combined treatment of
      chloramphenicol with amino acid yielded positive results in the management of
      anemia caused by chloramphenicol.

PMID- 16645428
TI  - Treatment of mild to moderate psoriasis with Relieva, a Mahonia aquifolium
      extract--a double-blind, placebo-controlled study.
AB  - Psoriasis is usually treated with local and systemic medications that have
      varying degrees of efficacy and safety profiles. We investigated the efficacy and
      safety of an alternative treatment from natural sources, Mahonia aquifolium, for
      the management of mild to moderate psoriasis. Two hundred subjects participated
      in a randomized, double-blind, placebo-controlled study using either the topical
      cream Relieva (a homeopathic product containing a proprietary M. aquifolium
      extract) or control (placebo) twice a day for 12 weeks. Efficacy and safety were
      assessed using the Psoriasis Area Severity Index (PASI) and the Quality of Life
      Index (QLI) questionnaires at different times throughout the 12-week study. The
      PASI was evaluated by the physician at the beginning (week 0) and end (week 12)
      of the study. The QLI was assessed by patients at weeks 0, 4, 8, and 12. The
      results indicate statistically significant (P < 0.05) improvements in PASI and
      QLI in the Mahonia-treated group, compared with the control group. The side
      effects reported were infrequent, < 1% and minor; the most frequent side effects
      were rash, a burning sensation when applying the cream, and clothing stain. These
      data indicate that Relieva, a proprietary form of M. aquifolium, is effective and
      well tolerated in patients with mild to moderate psoriasis.

PMID- 16645429
TI  - Quality of Japanese clinical trials estimated from good clinical practice audit
      findings.
AB  - To describe qualitatively recent changes in the Japanese clinical trial
      environments, we compared the results of the Good Clinical Practice (GCP) audits
      conducted from April 1997 to March 2000 (FY1997 to FY1999) with those from April
      2002 to March 2003 (FY2002). In addition, the audit results were compared between
      the United States and Japan. The audit findings in the former period were based
      on the official audits by the Organization for Pharmaceutical Safety and Research
      (OPSR) that covered 331 hospitals and 775 trials. The audits by the OPSR in the
      latter period targeted 136 hospitals and 226 trials. The total number of
      deficiencies detected in the Good Clinical Practice audits in the former 3-year
      period (FY1997 to FY1999) was 1529, and the number in the single year (FY2002)
      was 1627. The total number of deficiencies detected and reported was about 3-fold
      on an annual basis between the periods. By category of deficiencies, there were 2
      remarkable changes in the OPSR's audit findings between FY1997-FY1999 and FY2002.
      One was an increase in the proportion of protocol deviations from 14.7%
      (225/1529) in FY1997-FY1999 to 48.2% (785/1627) in FY2002, and the other was a
      decrease in the proportion of case report form-related deficiencies from 43.6%
      (666/1529) to 16.0% (260/1627). The high prevalence of protocol nonadherence and
      the relatively few findings of informed consent errors were important
      characteristics of Japanese trials inferred from the audit result reported by the
      OPSR in FY2002. In the United States, relatively high proportions of protocol
      nonadherence and informed consent errors were observed in the audit finding
      reported in 1997. Although the audit results for clinical trials between the
      United States and Japan are not strictly comparable, our results suggest that
      protocol deviations are a compelling issue for quality improvement in the conduct
      of clinical trials for the 2 regions.

PMID- 16645430
TI  - Risk and short-term prognosis of myocardial infarction among users of
      antidiabetic drugs.
AB  - Old sulphonylureas have been linked with adverse cardiovascular effects; however,
      data on the clinical implications are sparse. We examined the association between
      use of sulphonylureas and other antidiabetic drugs and the risk and case fatality
      rate (CFR) of myocardial infarction (MI) in a population-based case-control and
      follow-up study, respectively. A total of 6738 cases of first-time MI and 67,374
      age- and gender-matched population controls were identified from the Hospital
      Discharge Registry and the Civil Registration System of North Jutland County,
      Denmark, in the period 1994 through 2002. Prescriptions for antidiabetic drugs
      before the index date were retrieved from a prescription database. We estimated
      odds ratios (ORs) of MI (case-control study) and 30-day CFR (follow-up study)
      associated with antidiabetic drug use adjusted for possible confounding factors
      and using nondiabetic subjects as the reference group. The risk of MI appeared
      higher among users of old sulphonylureas (adjusted OR, 2.07; 95% confidence
      interval (CI), 1.81-2.37) than among users of new sulphonylureas (adjusted OR,
      1.36; 95% CI, 1.01-1.84). The adjusted ORs among users of nonsulphonylurea oral
      antidiabetic drugs, insulin, and patients with diabetes not receiving
      pharmacotherapy were 1.38 (95% CI, 0.90-2.11), 2.56 (95% CI, 2.16-3.03), and 3.51
      (95% CI, 2.92-4.22), respectively. The overall 30-day CFR was 24.6%, but varied
      between 9.5% and 37.0% among the different categories. New sulphonylureas may be
      associated with a lower risk of MI than old sulphonylureas. Furthermore, the 30
      day CFR may vary according to type of antidiabetic drug. These differences
      indicate the need for further examination of the cardiovascular safety of
      antidiabetic drugs.

PMID- 16645431
TI  - Preclinical development of new drugs that enhance thyroid hormone metabolism and
      clearance: inadequacy of using rats as an animal model for predicting human risks
      in an IND and NDA.
AB  - New drugs that enhance metabolism or clearance of thyroid hormones in rats often
      trigger a sequence of toxicity events during chronic administration: reduction of
      thyroxine, elevation of thyroid-stimulating hormone (TSH) levels, and thyroid
      gland hyperfunction/growth. Hepatocellular hypertrophy and thyroid follicular
      hyperplasia are often observed with increased liver and thyroid organ weights.
      This unique toxicity profile seems to be species-specific because the thyroxine
      in rodents is metabolized rapidly, without thyroid hormone-binding globulin that
      serves as a reserve, as in humans. Thus, elevations of TSH were not reported in
      humans for drugs such as delavirdine, fluvastatin, nicardipine, phenobarbital,
      simvastatin, and spironolactone, all of which produce thyroid hyperplasia or
      tumors in rats. Further, the human thyroid is less sensitive to prolonged TSH
      stimulation than that of the rat (eg, endemic goiter patients with high TSH due
      to iodine deficiency do not develop thyroid cancer). In view of the species
      difference in sensitivity of the thyroid between rodents and humans, using the
      rat as an animal model to explore target organs of toxicity for a new drug that
      significantly enhances thyroid hormone metabolism/clearance and increases TSH
      levels would not be adequate. In this case, a compromised and dysfunctional
      hypothalamo-pituitary-thyroid system would confound the toxicity profile explored
      in preclinical toxicity testing and render the model an inadequate risk predictor
      for the new drug in humans. Under such conditions, IND and NDA sponsors of drugs
      exhibiting this activity profile should be encouraged to use alternative animal
      species for toxicity exploration to provide a more meaningful human risk
      prediction.

PMID- 16645432
TI  - Management of the cardinal features of andropause.
AB  - There are several problems facing aging men, especially sexual dysfunction,
      hypogonadism, and psychologic changes. This constellation of changes is sometimes
      referred to as "manopause" or "andropause." Unlike the dramatic changes in the
      hormonal milieu occurring during menopause in women, the age-related changes in
      reproductive hormones of men are subtle and occur gradually throughout the years
      of mature life. It has been estimated that circulating testosterone (T) declines
      longitudinally from age 19 at an average rate of 1% per year. The free or
      dialyzable fraction of serum T and the bioavailable (the sum of free fraction and
      loosely bound to albumin fraction) T decline more rapidly with age. Although the
      essential role of androgens in reproductive tissue development and emergence of
      secondary sex characteristics is well known, their role in adult sexual function
      seems to be primarily facultative. The effect of T on the central nervous system
      extends beyond sexual behavior. T has been shown to alter mood, memory, ability
      to concentrate, and the overall sense of vigor and well being that may interact
      with a host of other psychologic changes associated with aging. Disordered
      erectile function is not generally an endocrine problem but rather vascular,
      neurologic, and psychogenic in origin. It also may be the first sign of systemic
      vascular disease. The clinical management of andropause requires an
      individualized approach. In some men, the main problem may be psychologic,
      whereas in others, hypogonadism may play an important role. Many with erectile
      failure, suffer silently regardless of its etiology. In this review, we suggest
      some practical guidelines for the management of these conditions.

PMID- 16645433
TI  - Hydroxocobalamin as a cyanide antidote.

PMID- 16645434
TI  - Androgen receptor as a therapeutic target for androgen independent prostate
      cancer.
AB  - Prostate cancer is the leading cause of nonskin malignancy and the second leading
      cause of cancer death in men. Androgen deprivation therapy is the first-line of
      systemic therapy against advanced prostate cancer. All advanced prostate cancers
      eventually grow despite castrate levels of testosterone. We review the evidence
      that androgen independent prostate cancer continues to require androgen receptor
      activity for growth, the mechanisms of androgen receptor activation in the
      castrate setting, and possible points of intervention for novel therapies
      targeting the androgen receptor and prostate cancer.

PMID- 16645435
TI  - Resolving hyperlipidemia after liver transplantation in a patient with primary
      sclerosing cholangitis.
AB  - A 64-year-old man with primary sclerosing cholangitis (PSC) and resultant liver
      failure presented to our hospital with severe dyslipidemia (total cholesterol,
      525 mg/dL; low-density lipoprotein (LDL) cholesterol, 489 mg/dL; high-density
      lipoprotein (HDL) cholesterol, 13 mg/dL; triglycerides, 114 mg/d) and coronary
      artery disease. The abnormal lipid profile of patients with cholestatic liver
      disease, such as PSC, includes an abnormal atherogenic LDL called lipoproteinX.
      The patient's dyslipidemia persisted despite treatment with a statin. Lipids
      normalized only after liver transplantation (total cholesterol, 135 mg/dL; LDL
      cholesterol, 60 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL;
      triglycerides, 130 mg/dL). To the best of our knowledge, the dramatic improvement
      in the lipid profile after liver transplantation represents the first such
      published report for PSC. The recognition of dyslipidemia and atherosclerosis in
      those with cholestatic liver disease and the normalization of lipid profile after
      liver transplantation warrant further study. We present a review of dyslipidemia
      in cholestatic liver disease, its relationship to atherosclerosis, and its
      treatment.

PMID- 16645436
TI  - Rare case of rhabdomyolysis with therapeutic doses of phendimetrazine tartrate.
AB  - Phendimetrazine tartrate is a newer drug that acts as a central stimulant and
      indirectly acting sympathomimetic with a host of uses similar to the class
      amphetamines. Its main use is as an anorectic in the short-term treatment of
      obesity, although stimulants are no longer indicated for this purpose. This drug
      appeals to the younger American population for immediate weight loss through
      decreased appetite and early satiety. The European Union markets have already
      withdrawn this medication as well as other countries, but phendimetrazine is
      still used within the United States. Rhabdomyolysis is a potentially life
      threatening complication reported with higher doses of amphetamines. We present a
      case of rhabdomyolysis and myoglobinuria developing in a 23-year-old patient
      after oral administration of phendimetrazine tartrate for 3 days in suggested
      therapeutic doses. The medication was taken for short-term treatment of obesity,
      and patient did not have any predisposing factors to precipitate rhabdomyolysis.
      Rhabdomyolysis resolved within 5 days. To our knowledge, this is the first
      reported case of rhabdomyolysis from administration of therapeutic amounts of
      phendimetrazine tartrate. The purpose of this case report is to create an
      awareness among physicians about the potentially life-threatening complications
      associated with phendimetrazine use as an anorectic even in suggested therapeutic
      doses as was the case in our patient. Additional awareness is needed to educate
      their patients about the side effects associated with these drugs and to strongly
      discourage their unsupervised use.

PMID- 16645438
TI  - Physiologic transfusion triggers: do we have to use (our) brain?

PMID- 16645439
TI  - Is there value in obtaining a patient's willingness to pay for a particular
      anesthetic intervention?

PMID- 16645440
TI  - Perspectives on the genetic basis of opioid-induced hyperalgesia.

PMID- 16645441
TI  - Fresh blood and aged stored blood are equally efficacious in immediately
      reversing anemia-induced brain oxygenation deficits in humans.
AB  - BACKGROUND: Erythrocytes are transfused to treat or prevent imminent inadequate
      tissue oxygenation. 2,3-diphosphoglycerate concentration decreases and oxygen
      affinity of hemoglobin increases (P50 decreases) with blood storage, leading some
      to propose that erythrocytes stored for 14 or more days do not release sufficient
      oxygen to make their transfusion efficacious. The authors tested the hypothesis
      that erythrocytes stored for 3 weeks are as effective in supplying oxygen to
      human tissues as are erythrocytes stored for less than 5 h. METHODS: Nine healthy
      volunteers donated 2 units of blood more than 3 weeks before they were tested
      with a standard, computerized neuropsychological test (digit-symbol substitution
      test [DSST]) on 2 days, 1 week apart, before and after acute isovolemic reduction
      of their hemoglobin concentration to 7.4 and 5.5 g/dl. Volunteers randomly
      received autologous erythrocytes stored for either less than 5 h ("fresh") or 3
      weeks ("stored") to return their hemoglobin concentration to 7.5 g/dl (double
      blinded). Erythrocytes of the alternate storage duration were transfused on the
      second experimental day. The DSST was repeated after transfusion. RESULTS: Acute
      anemia slowed DSST performance equivalently in both groups. Transfusion of stored
      erythrocytes with decreased P50 reversed the altered DSST (P < 0.001) to a time
      that did not differ from that at 7.4 g/dl hemoglobin during production of acute
      anemia (P = 0.88). The erythrocyte transfusion-induced DSST improvement did not
      differ between groups (P = 0.96). CONCLUSION: Erythrocytes stored for 3 weeks are
      as efficacious as are erythrocytes stored for 3.5 h in reversing the
      neurocognitive deficit of acute anemia. Requiring fresh rather than stored
      erythrocytes for augmentation of oxygen delivery does not seem warranted.

PMID- 16645442
TI  - Electroencephalographic approximate entropy changes in healthy volunteers during
      remifentanil infusion.
AB  - BACKGROUND: The aim of this study was to investigate the independent effect of
      remifentanil on the approximate entropy (ApEn) in frontoparietal montages. The
      authors investigated which montages were relevant to assess the remifentanil
      effect on the electroencephalogram. Spectral edge frequency and the canonical
      univariate parameter were used as comparators. METHODS: Twenty-eight healthy
      volunteers were enrolled. With recording of the electroencephalogram at the F3,
      F4, Cz, P3, and P4 montages, remifentanil was infused at the rate of 1-8 mug . kg
      . min for 15-20 min. The relation between remifentanil concentration and the
      electroencephalographic parameters were tested by Spearman correlation. Signal-to
      noise ratio, artifact robustness, coefficient of variation of the median baseline
      and maximal electroencephalographic effects, and ratio of average maximal
      electroencephalographic effect to interindividual baseline variability were
      measured. The performance of ApEn as an index of remifentanil effect site
      concentrations was tested by prediction probability. RESULTS: Approximate entropy
      showed significant correlation (R = -0.6465, P < 0.0001) with remifentanil
      concentration. It provided comparable signal-to-noise ratio, artifact robustness,
      and ratio of average maximal electroencephalographic effect to interindividual
      baseline variability to 95% spectral edge frequency. The coefficients of
      variation of the median baseline and maximal electroencephalo graphic effects
      were smallest in ApEn. Parietal montages showed higher ratios of average maximal
      electroencephalographic effect to interindividual baseline variability for all
      electroencephalographic parameters and lower coefficients of variation of the
      baseline values for ApEn and 95% spectral edge frequency than frontal montages.
      The prediction probability of ApEn was 0.7730. CONCLUSIONS: Approximate entropy
      derived from a parietal montage is appropriate for the assessment of the
      remifentanil effect on the electroencephalogram.

PMID- 16645443
TI  - Comparison of mucosal pressures induced by cuffs of different airway devices.
AB  - BACKGROUND: High pressures exerted by balloons and cuffs of conventional
      endotracheal tubes, the Combitube (Tyco Healthcare Nellcor Mallinckrodt,
      Pleasanton, CA), the EasyTube (Teleflex Ruesch, Kernen, Germany), the Laryngeal
      Mask Airway (LMA North America, San Diego, CA), the Intubating Laryngeal Mask
      Airway (Fastrach; LMA North America), the ProSeal (LMA North America), and the
      Laryngeal Tube (LT; VBM Medizintechnik, Sulz, Germany) may traumatize the
      pharyngeal mucosa. The aim of this study was to compare pressures exerted on the
      pharyngeal, tracheal, and esophageal mucosa by different devices designed for
      securing the patient's airways. METHODS: Nineteen fresh cadavers were included.
      To measure mucosal pressures, microchip sensors were fixed on the anterior,
      lateral, and posterior surfaces of the proximal balloon and the distal cuff of
      the investigated devices. Depending on the respective airway device, the cuff
      volume was increased in 10-ml increments at the proximal balloon starting from 0
      to a maximum of 100 ml, and in 2-ml increments at the distal cuff starting from 0
      up to 12 ml. RESULTS: Tracheal mucosal pressures were significantly higher using
      the Combitube compared with the endotracheal tube and the EasyTube. Maximal
      esophageal pressures were significantly higher using the EasyTube compared with
      the Combitube. Using cuff volumes according to the manufacturers' guidelines, we
      found the highest pharyngeal pressures with the Intubating Laryngeal Mask Airway
      versus all other devices. At maximal volumes, the Laryngeal Mask Airway, the
      Intubating Laryngeal Mask Airway, and the ProSeal induced significantly higher
      pharyngeal pressures compared with all other devices. Using a pharyngeal cuff
      volume of 40 ml, the Intubating Laryngeal Mask Airway followed by the Laryngeal
      Mask Airway exerted significantly higher pressures compared with the other
      devices. CONCLUSIONS: Although some devices exhibit a somewhat higher mucosal
      pressure when compared with others, the authors believe that the observed
      differences of the cuff pressures do not suggest a clinically relevant danger,
      because the investigated devices, except the endotracheal tubes, are not intended
      for prolonged use.

PMID- 16645444
TI  - Influence of the descending thoracic aortic cross clamping on bispectral index
      value and plasma propofol concentration in humans.
AB  - BACKGROUND: In this study, the authors investigated changes in Bispectral Index
      (BIS) values and plasma propofol concentrations (Cp) after aortic cross clamping
      in the descending thoracic aortic aneurysm repair surgery during propofol
      anesthesia. METHODS: Prospectively, in 10 patients undergoing thoracic aortic
      surgery during total intravenous anesthesia with propofol, BIS values were
      recorded during cross clamping of the descending thoracic aorta. In this study,
      the rate of propofol infusion was controlled to keep the BIS value between 30 and
      60 throughout surgery. Simultaneously, Cp values in the blood samples taken from
      the right radial artery (area proximal to cross clamping) and the left femoral
      artery (area distal to cross clamping) were measured. RESULTS: Approximately 15
      min after initiating aortic cross clamping, BIS values in all cases started to
      decrease abruptly. Cp values of samples taken from the radial artery after cross
      clamping of the aorta were significantly (P < 0.05) increased compared with pre
      cross clamp values (1.8 +/- 0.4 microg/ml), and the mean Cp after aortic cross
      clamping varied between 3.0 and 5.3 microg/ml. In addition, there were
      significant differences in the Cp values between radial arterial and femoral
      arterial blood samples throughout aortic cross clamping. Cp values in samples
      from the radial artery were approximately two to seven times higher than those
      from the femoral artery. CONCLUSIONS: This study showed that Cp values increased
      and BIS values decreased rapidly after aortic cross clamping in thoracic aortic
      aneurysm repair surgery during propofol anesthesia. These findings suggested that
      all anesthesiologists should control the infusion rate carefully, taking the
      abrupt changes in its pharmacokinetics into consideration, especially during
      cross clamping of the descending thoracic aorta.

PMID- 16645445
TI  - Mild hypercapnia increases subcutaneous and colonic oxygen tension in patients
      given 80% inspired oxygen during abdominal surgery.
AB  - BACKGROUND: Supplemental perioperative oxygen increases tissue oxygen tension and
      decreases incidence of wound infection in colorectal surgery patients. Mild
      intraoperative hypercapnia also increases subcutaneous tissue oxygen tension.
      However, the effect of hypercapnia in patients already receiving supplemental
      oxygen is unknown, as is the effect of mild hypercapnia on intestinal oxygenation
      in humans-although the intestines are presumably the tissue of interest for colon
      surgeries. The authors tested the hypothesis that mild intraoperative hypercapnia
      increases both subcutaneous tissue and intramural intestinal oxygen tension in
      patients given supplemental oxygen. METHODS: Patients undergoing elective colon
      resection were randomly assigned to normocapnia (n = 15, end-tidal carbon dioxide
      tension 35 mmHg) or mild hypercapnia (n = 15, end-tidal carbon dioxide tension 50
      mmHg). Intraoperative inspired oxygen concentration was 80%. The authors measured
      subcutaneous tissue oxygen tension in the right upper arm and intramural oxygen
      tension in the left colon. Measurements were averaged over time within each
      patient and, subsequently, among patients. Data were compared with chi-square,
      unpaired t, or Mann-Whitney rank sum tests; P < 0.05 was significant. RESULTS:
      Morphometric characteristics and other possible confounding factors were similar
      in the groups. Intraoperative tissue oxygen tension in hypercapnic patients was
      significantly greater in the arm (mean +/- SD: 116 +/- 29 mmHg vs. 84 +/- 25
      mmHg; P = 0.006) and colon (median [interquartile range]: 107 [81-129] vs. 53 [41
      104] mmHg; P = 0.020). CONCLUSIONS: During supplemental oxygen administration,
      mild intraoperative hypercapnia increased tissue oxygen tension in the arm and
      colon. Previous work suggests that improved tissue oxygenation will reduce
      infection risk via the proposed pathomechanism, although only an outcome study
      can confirm this.

PMID- 16645446
TI  - Geographic regional differences in rocuronium bromide dose-response relation and
      time course of action: an overlooked factor in determining recommended dosage.
AB  - BACKGROUND: Geographic location is not acknowledged as a stratifying factor that
      can directly affect drug potency, because drugs are still licensed with the same
      recommended dose for different geographic regions. The aim of the current study
      was to compare the potency and duration of action of rocuronium bromide in 54
      patients in three countries with different life habits, diet, and ambient
      conditions, namely white Austrians, white North Americans, and Han Chinese in
      China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium
      incremental doses followed by 300 microg/kg was evaluated using the Relaxometer
      mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves
      were created using log-dose-probit transformation. The authors compared
      rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%,
      and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times
      from last incremental dose administration until 25% first twitch and 0.8 train-of
      four ratio recovery, respectively) in patients of the three countries. RESULTS:
      Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients
      (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/
      59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148
      +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8
      were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8
      min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with
      American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively).
      CONCLUSIONS: The authors demonstrated a significant difference in rocuronium
      potency and duration of action among patients in the three countries. Larger
      studies are required for determining dosage recommendations for different
      geographic regions.

PMID- 16645447
TI  - Determination of endotracheal tube size in a perinatal population: an anatomical
      and experimental study.
AB  - BACKGROUND: This study aimed at correlating anatomical dimensions of the larynx
      and trachea to age and weight in a prenatal population. Endotracheal tube size
      determination was then proposed according to these considerations. METHODS:
      Anatomical measurements were obtained during 150 fetal and infant postmortem
      examinations. The optimal endotracheal tube size was determined by three methods:
      clinically, by a pressure method using calibrated inextensible balloons, and
      anatomically by comparing the laryngotracheal perimeter to the tube perimeters.
      Based on these results, recommended tube sizes were calculated. RESULTS: In
      premature babies before 37 weeks gestation, the optimal tube size according to
      pressure estimation was significantly greater than that determined by anatomical
      measurement alone. This difference was no longer valid after 40 weeks gestation.
      CONCLUSIONS: This study identified the elasticity of laryngeal structures in
      premature babies, allowing intubation with tube sizes greater than predicted by
      anatomical measurements with an increasing injury risk located in the posterior
      part of the glottic plane. This elasticity disappears near 40 weeks gestation,
      and the injury risk then predominates in the subglottic region. These results
      lead the authors to recommend that the size of the endotracheal tube used in the
      perinatal population should be based on anatomical and experimental data to limit
      the injury risks.

PMID- 16645448
TI  - Ropivacaine decreases inflammation in experimental endotoxin-induced lung injury.
AB  - BACKGROUND: Endotoxin causes acute lung injury, which can lead to acute
      respiratory distress syndrome. Because local anesthetics are known to attenuate
      inflammatory reactions, ropivacaine was tested for its possible antiinflammatory
      effect in lipopolysaccharide-induced lung injury in rat alveolar epithelial cells
      (AECs) and rat pulmonary artery endothelial cells (RPAECs) in vitro and in vivo.
      METHODS: AECs and RPAECs were stimulated for 4 h with lipopolysaccharide or
      lipopolysaccharide and 1 mum ropivacaine. Messenger RNA (mRNA) for intercellular
      adhesion molecule 1 was assessed. Isolated neutrophils were incubated with
      stimulated target cells to quantify adhesion and neutrophil-induced cytotoxicity
      in AECs and RPAECs. In vivo, lipopolysaccharide was instilled intratracheally
      with or without 1 mm intratracheally or intravenously administered ropivacaine.
      Bronchoalveolar lavage was performed 5 h later to determine neutrophil and
      albumin content, as well as concentrations of inflammatory mediators. RESULTS: In
      AECs and RPAECs, ropivacaine attenuated lipopolysaccharide-induced up-regulation
      of mRNA for intercellular adhesion molecule 1 by 41% and 24%, respectively (P <
      0.05). In the presence of ropivacaine, increased neutrophil adhesion was down
      regulated by 58% and 44% (P < 0.005), whereas cytotoxicity in AECs and RPAECs was
      diminished by 28% and 33%, respectively (P < 0.05). Enhanced neutrophil count in
      lipopolysaccharide lungs was reduced by 56% in the presence of intratracheally
      instilled ropivacaine (81% with intravenous ropivacaine; P < 0.005). Albumin was
      decreased by 46% with intratracheal ropivacaine (38% with intravenous
      ropivacaine; P < 0.05), and inflammatory mediators were decreased by 48-59% (69
      81% with intravenous ropivacaine; P < 0.01). CONCLUSIONS: Ropivacaine
      intervention substantially attenuated the inflammatory response in acute lung
      injury and thus may carry an interesting potential for antiinflammatory
      treatment.

PMID- 16645449
TI  - Propofol-induced activation of protein kinase C isoforms in adult rat ventricular
      myocytes.
AB  - BACKGROUND: Myocardial protection by anesthetics is known to involve activation
      of protein kinase C (PKC). The authors' objective was to identify the PKC
      isoforms activated by propofol in rat ventricular myocytes. They also assessed
      the intracellular location of individual PKC isoforms before and after treatment
      with propofol. METHODS: Freshly isolated ventricular myocytes were obtained from
      adult rat hearts. Immunoblot analysis of cardiomyocyte subcellular fractions was
      used to assess translocation of individual PKC isoforms before and after exposure
      to propofol. An enzyme-linked immunosorbent assay kit was used for measuring PKC
      activity. Immunocytochemistry and confocal microscopy were used to visualize the
      intracellular location of the individual PKC isoforms. RESULTS: Under baseline
      conditions, PKC-alpha, PKC-delta, and PKC-zeta were associated with both the
      cytosolic and membrane fractions, whereas PKC-epsilon was exclusively located in
      the cytosolic fraction. Propofol (10 microM) caused translocation of PKC-alpha,
      PKC-delta, PKC-epsilon, and PKC-zeta from cytosolic to membrane fraction and
      increased total PKC activity (211 +/- 17% of baseline; P = 0.003) in a dose
      dependent manner. Immunocytochemical localization of the individual PKC isoforms
      demonstrated that propofol caused translocation of PKC-alpha to the intercalated
      discs and z-lines; PKC-delta to the perinuclear region; PKC-epsilon to sites
      associated with the z-lines, intercalated discs, and the sarcolemma; and PKC-zeta
      to the nucleus. CONCLUSIONS: These results demonstrate that propofol causes an
      increase in PKC activity in rat ventricular myocytes. Propofol stimulates
      translocation of PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta to distinct
      intracellular sites in cardiomyocytes. This may be a fundamentally important
      cellular mechanism of anesthesia-induced myocardial protection in the setting of
      ischemia-reperfusion injury.

PMID- 16645450
TI  - Propofol decreases myofilament Ca2+ sensitivity via a protein kinase C-, nitric
      oxide synthase-dependent pathway in diabetic cardiomyocytes.
AB  - BACKGROUND: The authors' objective was to assess the role of protein kinase C
      (PKC) and nitric oxide synthase (NOS) in mediating the effects of propofol on
      diabetic cardiomyocyte contractility, intracellular free Ca2+ concentration
      ([Ca2+]i), and myofilament Ca2+ sensitivity. METHODS: Freshly isolated
      ventricular myocytes were obtained from normal and diabetic rat hearts. [Ca2+]i
      and cell shortening were simultaneously measured in electrically stimulated,
      ventricular myocytes using fura-2 and video-edge detection, respectively.
      Actomyosin adenosine triphosphatase activity and troponin I (TnI) phosphorylation
      were assessed in [32P]orthophosphate-labeled myofibrils. Western blot analysis
      was used to assess expression of PKC and NOS. RESULTS: Propofol (10 microM)
      decreased peak shortening by 47 +/- 6% with little effect on peak [Ca2+]i (92 +/-
      5% of control) in diabetic myocytes. Maximal actomyosin adenosine triphosphatase
      activity was reduced by 43 +/- 7% and TnI phosphorylation was greater (32 +/- 6%)
      in diabetic myofibrils compared with normal. Propofol reduced actomyosin
      adenosine triphosphatase activity by 17 +/- 7% and increased TnI phosphorylation
      in diabetic myofibrils. PKC inhibition prevented the propofol-induced increase in
      TnI phosphorylation and decrease in shortening. Expression of PKC-alpha, PKC
      delta, PKC-epsilon, and constitutive NOS were up-regulated and inducible NOS was
      expressed in diabetic cardiomyocytes. NOS inhibition attenuated the propofol
      induced decrease in shortening. CONCLUSION: Myofilament Ca2+ sensitivity and, to
      a lesser extent, peak [Ca2+]i are decreased in diabetic cardiomyocytes. Increases
      in PKC and NOS expression in combination with TnI phosphorylation seem to
      contribute to the decrease in [Ca2+]i and myofilament Ca2+ sensitivity. Propofol
      decreases [Ca2+]i and shortening via a PKC-, NOS-dependent pathway.

PMID- 16645451
TI  - The common inhalation anesthetic isoflurane induces apoptosis and increases
      amyloid beta protein levels.
AB  - BACKGROUND: The common inhalation anesthetic isoflurane has previously been
      reported to enhance the aggregation and cytotoxicity of the Alzheimer disease
      associated amyloid beta protein (Abeta), the principal peptide component of
      cerebral beta-amyloid deposits. METHODS: H4 human neuroglioma cells stably
      transfected to express human full-length wild-type amyloid precursor protein
      (APP) were exposed to 2% isoflurane for 6 h. The cells and conditioned media were
      harvested at the end of the treatment. Caspase-3 activation, processing of APP,
      cell viability, and Abeta levels were measured with quantitative Western
      blotting, cell viability kit, and enzyme-linked immunosorbent assay sandwich. The
      control condition consisted of 5% CO2 plus 21% O2 and balanced nitrogen, which
      did not affect caspase-3 activation, cell viability, APP processing, or Abeta
      generation. RESULTS: Two percent isoflurane caused apoptosis, altered processing
      of APP, and increased production of Abeta in H4 human neuroglioma cell lines.
      Isoflurane-induced apoptosis was independent of changes in Abeta and APP
      holoprotein levels. However, isoflurane-induced apoptosis was potentiated by
      increased levels of APP C-terminal fragments. CONCLUSION: A clinically relevant
      concentration of isoflurane induces apoptosis, alters APP processing, and
      increases Abeta production in a human neuroglioma cell line. Because altered
      processing of APP leading to accumulation of Abeta is a key event in the
      pathogenesis of Alzheimer disease, these findings may have implications for use
      of this anesthetic agent in individuals with excessive levels of cerebral Abeta
      and elderly patients at increased risk for postoperative cognitive dysfunction.

PMID- 16645452
TI  - Isoflurane neuroprotection in rat hippocampal slices decreases with aging:
      changes in intracellular Ca2+ regulation and N-methyl-D-aspartate receptor
      mediated Ca2+ influx.
AB  - BACKGROUND: Most in vitro neuroprotection studies with isoflurane have involved
      cells obtained during the embryonic or early postnatal period. However, in mature
      rodents, isoflurane neuroprotection does not persist. The authors determined
      whether neuroprotection of hippocampal slices with isoflurane decreases with
      aging and is due to decreased intracellular Ca regulation and survival protein
      phosphorylation. METHODS: Hippocampal slices from 5-day-old, 1-month-old, and 19-
      to 23-month-old rats were deprived of oxygen and glucose for 5-30 min in media
      bubbled with 1% isoflurane. Cell death was assessed in the CA1, CA3, and dentate
      regions, and intracellular Ca concentration was measured in CA1 neurons. N-methyl
      d-aspartate receptor (NMDAR)-dependent Ca influx was measured and the
      phosphorylation of NMDARs, and the survival proteins Akt and mitogen-activated
      protein kinase p42/44 were quantified. RESULTS: Twenty minutes of oxygen and
      glucose deprivation killed approximately 40-60% of neurons in CA3 and dentate in
      all age groups. Isoflurane, 1%, reduced death of CA1, CA3, and dentate neurons in
      slices from 5-day-old rats but not those from 23-month-old rats. In 5-day slices,
      isoflurane attenuated NMDAR-mediated Ca influx, whereas in aging slices, Ca
      influx was increased protein kinase C. In aging slices, isoflurane did not
      increase the phosphorylation of Akt and p42/44. CONCLUSIONS: Isoflurane
      neuroprotection of hippocampal slices during oxygen and glucose deprivation
      decreases with age. Isoflurane does not prevent large increases in intracellular
      Ca concentration during oxygen and glucose deprivation and does not induce the
      phosphorylation of the prosurvival proteins in aging slices. A protein kinase C
      mediated increase in NMDAR activity may result in increased excitotoxicity and
      decreased neuroprotection by volatile anesthetics in the aging brain.

PMID- 16645453
TI  - Infarct-remodeled myocardium is receptive to protection by isoflurane
      postconditioning: role of protein kinase B/Akt signaling.
AB  - BACKGROUND: Postinfarct remodeled myocardium exhibits numerous structural and
      biochemical alterations. So far, it is unknown whether postconditioning elicited
      by volatile anesthetics can also provide protection in the remodeled myocardium.
      METHODS: Myocardial infarct was induced in male Wistar rats by ligation of the
      left anterior descending coronary artery. Six weeks later, hearts were buffer
      perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion.
      Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some
      experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was
      coadministered with isoflurane. Masson's trichrome staining,
      immunohistochemistry, Western blot analysis, and reverse-transcription polymerase
      chain reaction served to confirm remodeling. In buffer-perfused hearts,
      functional recovery was recorded, and acute infarct size was measured using 1%
      triphenyltetrazolium chloride staining and lactate dehydrogenase release during
      reperfusion. Western blot analysis was used to determine phosphorylation of
      reperfusion injury salvage kinases including protein kinase B/Akt and its
      downstream targets after 15 min of reperfusion. RESULTS: Infarct hearts exhibited
      typical macroscopic and molecular changes of remodeling. Isoflurane
      postconditioning improved functional recovery and decreased acute infarct size,
      as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/-
      3% in anesthetic postconditioning; P < 0.05) and lactate dehydrogenase release.
      This protection was abolished by LY294002, which inhibited phosphorylation of
      protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta,
      endothelial nitric oxide synthase, and p70S6 kinase. CONCLUSIONS: Infarct
      remodeled myocardium is receptive to protection by isoflurane postconditioning
      via protein kinase B/Akt signaling. This is the first time to demonstrate that
      anesthetic postconditioning retains its marked protection in diseased myocardium.

PMID- 16645454
TI  - Mechanisms underlying the QT interval-prolonging effects of sevoflurane and its
      interactions with other QT-prolonging drugs.
AB  - BACKGROUND: Sevoflurane prolongs ventricular repolarization in patients, but the
      mechanisms are not fully characterized. The effects of sevoflurane on many cloned
      human cardiac ion channels have not been studied, and the interactions between
      sevoflurane and other drugs that prolong cardiac repolarization have not been
      detailed. METHODS: The effects of sevoflurane on action potentials and L-type Ca
      channels in guinea pig myocytes were examined. Sevoflurane's effects on cloned
      human cardiac K channels and the cloned human cardiac Na channel were studied.
      The consequences of combining sevoflurane and the class III antiarrhythmic drugs
      sotalol or dofetilide on action potential duration were also examined. RESULTS:
      Sevoflurane produced an increase in action potential duration at concentrations
      of 0.3-1 mm. Contrary to most drugs that delay ventricular repolarization,
      sevoflurane was without effect on the human ether-a-go-go-related gene cardiac
      potassium channel but instead produced a reduction in KvLQT1/minK K channel
      currents and inhibited the Kv4.3 K channel by speeding its apparent rate of
      inactivation. Sevoflurane had little effect on Na and Ca channel currents at
      concentrations of 1 mm or less. When the authors coadministered sevoflurane with
      sotalol or dofetilide, synergistic effects on repolarization were observed,
      resulting in large increases in action potential duration (up to 66%).
      CONCLUSION: Prolonged ventricular repolarization observed with administration of
      sevoflurane results from inhibition of KvLQT1/minK and Kv4.3 cardiac K channels.
      Combining sevoflurane with class III antiarrhythmic drugs results in supra
      additive effects on action potential duration. The results indicate that
      sevoflurane, when administered with this class of drug, could result in excessive
      delays in ventricular repolarization. The results suggest the need for further
      clinical studies.

PMID- 16645455
TI  - Orexins increase cortical acetylcholine release and electroencephalographic
      activation through orexin-1 receptor in the rat basal forebrain during isoflurane
      anesthesia.
AB  - BACKGROUND: Cholinergic arousal system plays an important role in the maintenance
      of consciousness. The authors investigated whether the intrabasalis injection of
      orexin-A or orexin-B and the electrically stimulated pedunculopontine tegmentum
      nuclei (PPTg: the origin of cholinergic ascending pathways) may alter
      acetylcholine efflux and electroencephalographic activity in the somatosensory
      cortex in relation to the orexinergic system in isoflurane-anesthetized rats.
      METHODS: Either orexin-A (10, 30, or 100 pmol) or orexin-B (10, 30, or 100 pmol)
      (n = 6 each) was injected into the basal forebrain while the electroencephalogram
      was measured during 1.0 minimum alveolar concentration (1.2%) isoflurane
      anesthesia. Injection of Ringer's solution was used as a control. The PPTg was
      electrically stimulated twice with the following conditions: 1-s stimulus train
      (0.2 ms, 100 Hz, 400 microA) per min for 20 min. Twenty minutes before the second
      PPTg stimulation, Ringer's solution or 20 microg SB334867, an orexin-1 receptor
      antagonist (n = 5 each) was injected into the basal forebrain. RESULTS: Injection
      of orexin-A (30 and 100 pmol) and orexin-B (100 pmol) significantly increased the
      acetylcholine efflux in the somatosensory cortex (P < 0.05). Injection of orexin
      A (10, 30, 100 pmol) and orexin-B (30, 100 pmol) changed the burst and
      suppression patterns to arousal electroencephalogram. Compared with orexin-B,
      injection of a lower dose of orexin-A induced increase in the acetylcholine
      efflux and arousal electroencephalogram. SB334867 significantly attenuated the
      increases in the acetylcholine efflux and electroencephalographic activation
      evoked by PPTg stimulation. CONCLUSION: The authors demonstrated that orexin-A
      was more potent than orexin-B in producing alteration of cholinergic basal
      forebrain neuronal activity and that the cortical activation induced by the PPTg
      stimulation against isoflurane anesthesia may be mediated through the orexin-1
      receptors in the basal forebrain.

PMID- 16645456
TI  - Effect of postoperative experiences on willingness to pay to avoid postoperative
      pain, nausea, and vomiting.
AB  - BACKGROUND: The authors assessed the willingness to pay (WTP) for "perfect"
      prophylactic antiemetics and analgesics in patients who were scheduled to undergo
      surgery during general anesthesia. Furthermore, they determined whether
      postoperative experiences of pain and nausea and vomiting (PONV) changed
      patients' WTP. METHODS: Data were collected alongside a randomized clinical trial
      that investigated the incidence of PONV in patients anesthetized with either
      inhalation anesthesia or total intravenous anesthesia. A subset of 808
      consecutive patients participating in the trial completed WTP questionnaires 1
      day before and 2 weeks after surgery. The outcome measure was the maximum amount
      of money that patients were willing to pay for "perfect" antiemetics and
      analgesics. Preoperative WTP and individual WTP changes after surgery were
      analyzed in relation to baseline characteristics and postoperative pain and PONV
      experiences. RESULTS: Prevention of postoperative pain was valued higher than
      prevention of PONV. The median preoperative WTP for analgesics was US dollar 35
      (interquartile range, dolalr 7-69) vs. US dollar 17 (interquartile range, dollar
      7-69) for antiemetics. Individual WTP changes for antiemetics were not related to
      PONV experience, whereas severe postoperative pain (numerical rating score > or =
      8) was associated with an increase in the WTP for analgesics. CONCLUSIONS: Severe
      postoperative pain experiences increased patients' WTP for analgesics, but PONV
      did not increase WTP for antiemetics. The elicited WTP values were lower than
      those reported in previous studies, which is possibly related to differences in
      market culture or patients' attitudes toward postoperative pain, nausea, and
      vomiting.

PMID- 16645457
TI  - A multicenter dose-escalation study of the analgesic and adverse effects of an
      oral cannabis extract (Cannador) for postoperative pain management.
AB  - BACKGROUND: Cannabinoids have dose-related antinociceptive effects in animals.
      This clinical study aimed to investigate whether a single oral dose of cannabis
      plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany)
      could provide pain relief with minimal side effects for postoperative pain.
      METHODS: Patients (aged 18-75 yr) were recruited and consented before surgery if
      patient-controlled analgesia was planned for provision of postoperative pain
      relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or
      she had at least moderate pain after stopping patient-controlled analgesia.
      Starting with 5 mg, dose escalation was based on the number of patients
      requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and
      side effects were recorded over 6 h and analyzed using tests for trend with dose.
      RESULTS: Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg,
      15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15
      mg Cannador (log rank test for trend in time to rescue analgesia with dose P <
      0.001). There were also significant trends across the escalating dose groups for
      decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and
      more adverse events (P = 0.002). The number needed to treat to prevent one rescue
      analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95%
      confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7),
      respectively. The study was terminated because of a serious vasovagal adverse
      event in a patient receiving 15 mg. CONCLUSION: These significant dose-related
      improvements in rescue analgesia requirements in the 10 mg and 15 mg groups
      provide a number needed to treat that is equivalent to many routinely used
      analgesics without frequent adverse effects.

PMID- 16645458
TI  - Efficacy of single-dose, multilevel paravertebral nerve blockade for analgesia
      after thoracoscopic procedures.
AB  - BACKGROUND: Although video-assisted thoracoscopic surgery for pulmonary resection
      is increasingly chosen over thoracotomy, the optimal analgesia regimen for
      thoracoscopy is unknown. The purpose of this trial was to compare the efficacy of
      analgesia from preoperative bupivacaine paravertebral nerve blockade with that
      from placebo injections. METHODS: Eighty adult patients undergoing unilateral
      thoracoscopic procedures were enrolled in a prospective, double-blinded,
      randomized clinical trial of preoperative, multilevel, single-dose paravertebral
      nerve blockade. Patients received six paravertebral injections with 5 ml of
      either 0.5% bupivacaine with 0.0005% epinephrine (treated, n = 40) or
      preservative-free saline (control, n = 40). Cumulative weight-adjusted
      intraoperative fentanyl and postoperative patient-controlled morphine usage,
      visual analog pain scores, and spirometry were used to compare efficacy of
      analgesia between groups. RESULTS: The treated group received significantly less
      intraoperative fentanyl compared with the control group (P = 0.003) and had a 31%
      smaller cumulative patient-controlled morphine dose (P = 0.03) in the 6 h after
      block placement. Within 6 h, treated patients also reported lower maximum pain
      scores (P = 0.02) and demonstrated less pain score variability (P = 0.01). No
      statistically significant difference in cumulative morphine usage existed at 12
      or 18 h after block placement. No significant difference in spirometry, cortisol
      levels, or cytokine production was found between treatments. CONCLUSIONS: Single
      dose paravertebral nerve blockade with bupivacaine is effective in reducing pain
      after thoracoscopic surgery, but only during the first 6 h after nerve blockade.
      Because of the limited duration of effect with currently available local
      anesthetic agents, the current data suggest that, at present, this technique is
      not indicated in the setting of thoracoscopic surgery.

PMID- 16645459
TI  - A genetic analysis of opioid-induced hyperalgesia in mice.
AB  - BACKGROUND: Opioid-induced hyperalgesia (OIH) is a syndrome of increased
      sensitivity to noxious stimuli, seen after both the acute and chronic
      administration of opioids, that has been observed in humans and rodent models.
      This syndrome may reduce the clinical utility of opioids in treating acute and
      chronic pain. METHODS: In these studies, the authors measured the propensity of
      15 strains of inbred mice to develop mechanical manifestations of OIH. These data
      were subjected to in silico genetic analysis, which resulted in the association
      of haplotypic blocks within or near several known genes. Both pharmacologic
      agents and transgenic mice were used to confirm the functional association of the
      most strongly linked gene with OIH. RESULTS: Both baseline mechanical nociceptive
      thresholds and the percentage changes in these thresholds after 4 days of
      morphine treatment were found to be highly strain dependent. The haplotypic
      blocks most strongly associated with the mechanical OIH data were located within
      the beta2 adrenergic receptor gene (beta2-AR). Using the selective beta2-AR
      antagonist butoxamine, the authors observed a dose-dependent reversal of OIH.
      Furthermore, deletion of the beta2-AR gene sharply reduced the mechanical
      allodynia present after morphine treatment in the wild-type mouse strain.
      Analysis of the associated beta2-AR haplotypic block identified single nucleotide
      polymorphisms potentially explaining in part the strain specific differences in
      OIH. CONCLUSIONS: Genetic variants of the beta2-AR gene seem to explain some part
      of the differences between various strains of mice to develop OIH. The
      association of this gene with OIH suggests specific pharmacologic strategies for
      reducing the impact of OIH on patients consuming opioids.

PMID- 16645460
TI  - Major histocompatibility complex haplotype is associated with postherpetic pain
      in mice.
AB  - BACKGROUND: Postherpetic neuralgia is one of the major complications of herpes
      zoster caused by the reactivation of varicella-zoster virus and is characterized
      by severe pain. The authors previously showed the association of a human major
      histocompatibility complex (MHC) haplotype with postherpetic neuralgia. This
      study was performed to experimentally confirm the role of MHC haplotype in the
      development of postherpetic pain using a mouse model of postherpetic pain, which
      corresponds to postherpetic neuralgia. METHODS: BALB/c mice (MHC haplotype: H-2),
      C57BL/6 mice (MHC haplotype: H-2), and BALB/b mice, a congenic BALB/c strain with
      H-2, were used. Herpes simplex virus type I was transdermally inoculated on the
      hind paw. Unilaterally zosteriform skin lesion and pain-related responses (acute
      herpetic pain) were caused, and some mice showed pain-related responses
      (postherpetic pain) after the cure of skin lesions. Herpes simplex virus type I
      antigen and CD3-positive cells were immunostained in the dorsal root ganglion in
      the acute phase. RESULTS: The incidence (78%) of postherpetic pain in C57BL/6
      mice was significantly higher than that (35%) in BALB/c mice (P = 0.004, odds
      ratio = 6.7). Furthermore, the incidence of postherpetic pain in BALB/b (H-2) was
      similar to that in C57BL/6. Herpes simplex virus type I antigen-positive cells
      were less in the dorsal root ganglion of C57BL/6 mice than that of BALB/c mice.
      CD3-positive T cells were more in the dorsal root ganglion of C57BL/6 mice than
      BALB/c mice. CONCLUSIONS: These results suggest that the MHC haplotype (H-2) is
      involved in the incidence of postherpetic pain, and CD3-positive T cells may play
      a role in its pathogenesis.

PMID- 16645461
TI  - Impact of hypothermia on the response to neuromuscular blocking drugs.
AB  - Muscle strength is reduced during hypothermia, both in the presence and in the
      absence of neuromuscular blocking drugs. A 2 degrees C reduction in body
      temperature may double the duration of neuromuscular blockade. Central body and
      muscle temperatures decline in parallel, as long as peripheral vasoconstriction
      does not occur. A reduction in muscle strength must be expected at a body
      temperature less than 36 degrees C (corresponding to a muscle temperature of
      approximately 35 degrees C). Local cooling of the hand may make adductor pollicis
      twitch tension monitoring less useful during clinical anesthesia. The efficacy of
      neostigmine is maintained during mild hypothermia. The use of a nerve stimulator
      is strongly recommended to monitor the effect of neuromuscular blocking drugs
      during intraoperative hypothermia.

PMID- 16645462
TI  - Practice guidelines for the perioperative management of patients with obstructive
      sleep apnea: a report by the American Society of Anesthesiologists Task Force on
      Perioperative Management of patients with obstructive sleep apnea.

PMID- 16645463
TI  - Who better than anesthesiologists? The 44th Rovenstine lecture.

PMID- 16645464
TI  - Obstetric anesthesia: the 1982 American College of Obstetricians and
      Gynecologists standards and the role of Robert E. Johnstone, M.D.

PMID- 16645466
TI  - Bring rapidly degradable hydroxyethyl starch to the United States.

PMID- 16645468
TI  - Proper priority please.

PMID- 16645469
TI  - Package inserts are a must read for anesthesiologists.

PMID- 16645471
TI  - Labeling (package insert): meaning by the Food and Drug Administration of not
      recommended, not indicated, and off-label use.

PMID- 16645472
TI  - Drug labels should evolve with medical knowledge.

PMID- 16645474
TI  - Botulinum toxin type a therapy and human serum albumin.

PMID- 16645475
TI  - The Datex-Ohmeda M-NMT Module: a potentially confusing user interface.

PMID- 16645477
TI  - Unforeseen esophageal misplacement of airway exchange catheter leading to gastric
      perforation.

PMID- 16645478
TI  - The use of safety needles in anesthesia.

PMID- 16645479
TI  - Use of ketamine to facilitate opioid withdrawal in a child.

PMID- 16645482
TI  - The role of bacteria in airway inflammation in exacerbations of chronic
      obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: Bacteria cause approximately half of all chronic obstructive
      pulmonary disease exacerbations. The purpose of this review is to evaluate the
      status of research on the role of bacteria in airway inflammation during
      exacerbations and the mechanisms by which bacterial antigens induce inflammation.
      RECENT FINDINGS: Bacteria in the airways of adults with chronic obstructive
      pulmonary disease release antigens including endotoxin, peptidoglycan fragments,
      lipoproteins, and other molecules into the airways. These bacterial antigens
      induce potent inflammatory effects in the airways. Bacterial exacerbations are
      associated with systemic inflammation. Studies of Haemophilus influenzae, the
      most common bacterial cause of exacerbations, reveal that strains associated with
      exacerbations induce more inflammation compared to colonizing strains. H.
      influenzae antigens induce production of interleukin-8 and tumor necrosis factor
      alpha, activate Toll-like 2 receptors, activate NFkappaB and p38 mitogen
      activated protein signaling pathways, and have other inflammatory effects.
      SUMMARY: Research on the role of bacteria in causing inflammation in chronic
      obstructive pulmonary disease has been neglected for decades. Research should be
      directed at further evaluating the role of bacterial antigens in airway
      inflammation. Reducing or modulating bacterial infection of the airways in
      chronic obstructive pulmonary disease has the potential to reduce airway
      inflammation by eliminating an important inciting cause.

PMID- 16645483
TI  - The role of high mobility group box-1 protein in severe sepsis.
AB  - PURPOSE OF REVIEW: Despite medical advances, mortality in severe sepsis remains
      high. As our understanding of the innate immune system has expanded, clinical
      trials have focused on inhibiting cytokines present early in the infectious
      process such as interleukin-1 and tumor necrosis factor-alpha, although with
      disappointing results. There is evidence that the nuclear protein high mobility
      group box-1 protein, when released extracellularly, acts as a persistent mediator
      of sepsis and is therefore a promising candidate for therapeutic intervention.
      This review summarizes current knowledge of the protein and highlights recent
      relevant findings. RECENT FINDINGS: High mobility group box-1 protein may be
      released into the circulation either due to necrosis of cells or by active
      release from macrophages and endothelial cells. Models of experimental sepsis in
      mice have shown a strong association between extracellular high mobility group
      box-1 protein and lethality. Treatments against the biological activities of high
      mobility group box-1 protein reduce lethality in these models. Other studies have
      shown high mobility group box-1 protein as a key regulator in acute and chronic
      inflammation. Recent findings confirm that high mobility group box-1 protein is
      persistently elevated in human patients with severe sepsis. SUMMARY: Despite all
      efforts, mortality in severe sepsis remains high. A massive amount of evidence
      indicates high mobility group box-1 protein as a delayed and important propagator
      of inflammation. Recent studies confirm persisting high levels of high mobility
      group box-1 protein in serum up to 1 week after hospitalization. Reducing levels
      of the protein by anti-high mobility group box-1 protein treatment may be one way
      to moderate uncontrolled inflammation seen in sepsis.

PMID- 16645484
TI  - Pathophysiology of interleukin-1 receptor-associated kinase-M: implications in
      refractory state.
AB  - PURPOSE OF REVIEW: The pseudo-kinase interleukin-1 receptor-associated kinase-M
      has emerged as a critical molecule in the down-regulation of inflammatory
      responses. Dysregulation of the toll-like receptor-interleukin-1 receptor
      associated kinase system, and in particular interleukin-1 receptor-associated
      kinase-M up-regulation, are associated with a number of pathologies. This review
      highlights recent findings on interleukin-1 receptor-associated kinase-M reported
      in biomedical literature. RECENT FINDINGS: Interleukin-1 receptor-associated
      kinase-M plays a critical role in generating a refractory state of the immune
      system following monocytes/macrophages encounter with bacteria or tumor cells.
      This state has been demonstrated so far in patients who suffer from sepsis,
      leukemia, and acute coronary syndrome, and seems to be associated with
      interleukin-1 receptor-associated kinase-M overexpression in their circulating
      monocytes. In addition, the pseudo-kinase represents a central regulator of
      osteoclast differentiation and activation, and might thus be related to the onset
      of osteoporosis. SUMMARY: Interleukin-1 receptor-associated kinase-M is involved
      in the control of endotoxin tolerance in monocytes, in osteoporosis, as well as
      in the deactivation of tumor-infiltrating macrophages. Additionally, patients who
      suffer from several pathologies related to inflammatory responses express high
      levels of this molecule in their circulating monocytes. Human monocytes treated
      with a nitric oxide donor also express large amounts of interleukin-1 receptor
      associated kinase-M, apparently under the control of tumor necrosis factor-alpha.
      This mechanism could explain the induction of interleukin-1 receptor-associated
      kinase-M in monocytes from patients who suffer from an inflammatory pathology.

PMID- 16645485
TI  - Rationale and safety of anti-interleukin-23 and anti-interleukin-17A therapy.
AB  - PURPOSE OF REVIEW: Interleukin-12 is a heterodimeric cytokine and an important
      mediator of the cellular immune response. The recent discovery of the novel
      cytokine interleukin-23 has led to a re-evaluation of interleukin-12 biology, as
      both cytokines use a common p40 subunit. This review discusses understanding of
      what distinguishes these related cytokines and the infection risks associated
      with targeting these cytokine pathways during treatment of inflammatory diseases.
      RECENT FINDINGS: Recent work has shown that interleukin-23 stimulates the
      development of a distinct subset of effector T cells that produce interleukin
      17A. These interleukin-17A-producing cells are critical mediators of the
      inflammatory response in several mouse models of autoimmunity. Although it is
      well established that interleukin-12 is a critical mediator of host defense, the
      role of the interleukin-23/interleukin-17A axis during infections has only
      recently been evaluated. SUMMARY: Interleukin-12 and interleukin-23 have distinct
      roles in mediating host defense and autoimmune inflammation. Although targeting
      interleukin-12 and interleukin-23 simultaneously against the common p40 subunit
      is efficacious in clinical trials for human autoimmune diseases, targeting of
      interleukin-23 alone or the downstream effector cytokine interleukin-17A may be
      an effective treatment strategy for organ-specific autoimmune diseases. It is
      likely that targeting interleukin-23 or interleukin-17A alone, as opposed to
      targeting interleukin-12 and interleukin-23 together, will reduce the patients'
      risk of developing treatment-related infections.

PMID- 16645486
TI  - Antenatal infection and inflammation: what's new?
AB  - PURPOSE OF REVIEW: Recently antenatal infection and inflammation have received
      significant attention because of their potential role in promoting premature
      labour and in causing morbidity in preterm infants including the development of
      chronic lung disease of prematurity and cerebral white matter changes. This
      review highlights recent developments in this field. RECENT FINDINGS: Recent
      reports have improved our understanding of the inflammatory responses to
      antenatal infection although questions remain about the exact relationship
      between antenatal infection and inflammation. Although microbial invasion of the
      intrauterine cavity is confirmed, strategies to prevent onset of premature labour
      have not been successful. The association between antenatal infection and
      development of chronic lung disease has been confirmed and many mechanisms
      further explored for development of chronic lung disease and cerebral white
      matter changes. Ureaplasma species have been revisited for their role in both
      preterm labour and neonatal morbidity, especially as modern molecular methods
      have eased their identification. SUMMARY: Antenatal infection and inflammation
      are strongly implicated in the pathogenesis of preterm labour and in the
      development of neonatal morbidity, specifically chronic lung disease and white
      matter damage. Ureaplasma species are being increasingly studied for their role
      in these disorders. The challenge is to develop effective therapies to prevent
      these conditions.

PMID- 16645487
TI  - Genetic susceptibility to neonatal infection.
AB  - PURPOSE OF REVIEW: To review current data on genetic factors contributing to the
      striking susceptibility of neonates to infectious diseases and other adverse
      outcomes. RECENT FINDINGS: Although few studies address genetic determinants of
      neonatal infectious disease susceptibility, several variants in genes involved in
      the innate immune response have been associated with differential risk for
      neonatal infection. The most consistent results relate to polymorphisms of tumour
      necrosis factor-alpha, whereas other gene polymorphisms, such as those of
      interleukin-6, have yielded conflicting findings. Similar genetic factors may be
      involved in other inflammatory neonatal diseases. Recent data suggest that
      genetic variation may influence the pace of immunologic maturation. SUMMARY:
      Despite the enormous human and financial costs of infection for neonatal
      mortality and morbidity worldwide, it remains unclear why neonates are so
      susceptible. Genetic epidemiologic studies may assist in the identification of
      critical protective and pathogenic pathways. Despite the current relative lack of
      robust data, such studies are likely to facilitate the development of
      interventions that ultimately decrease the significant morbidity and mortality of
      this highly vulnerable population.

PMID- 16645488
TI  - The innate immune system and its relevance to neonatal sepsis.
AB  - PURPOSE OF REVIEW: The advent of human Toll-like receptors has revolutionized our
      understanding of innate immunity. This review summarizes recent discoveries about
      the role of Toll-like receptors and innate immunity in neonatal sepsis with a
      particular emphasis on the paradigmatic organism S. agalactiae. RECENT FINDINGS:
      S. agalactiae stimulates phagocytes to excessive formation of inflammatory
      cytokines such as tumor necrosis factor, and Toll-like receptors are essential
      for this response both in vivo and in vitro. On the molecular level, distinct
      signaling pathways are engaged by released S. agalactiae toxins such as
      lipoteichoic acid (Toll-like receptor-2 dependent) and cell-bound toxins (Toll
      like receptor-2 independent). In contrast, complement receptors and Fc receptors,
      but not Toll-like receptors, are directly involved in phagocytosis and therefore
      elimination of S. agalactiae. Notably, neonatal phagocytes potently activate
      cytokines in response to S. agalactiae but are deficient in S. agalactiae uptake
      and killing. Interference with the Toll-like receptor-dependent mitogen activated
      protein kinase cJun N-terminal Kinase improves outcome in a neonatal model of S.
      agalactiae sepsis by inhibiting cytokine formation but preserving clearance of S.
      agalactiae. SUMMARY: Recent progress in the understanding of S. agalactiae
      recognition and phagocytic signaling in neonatal sepsis suggests intermediates in
      the Toll-like receptor pathways as valuable targets for adjunctive sepsis
      therapy.

PMID- 16645489
TI  - Prospects for prevention of childhood infections by maternal immunization.
AB  - PURPOSE OF REVIEW: To review the literature on using maternal immunization as a
      strategy to prevent infections in young infants aged below 6 months RECENT
      FINDINGS: Maternal immunization continues to reduce the incidence of neonatal
      tetanus worldwide. Despite increased influenza-related morbidity and mortality in
      pregnant women and in infants aged less than 6 months, compliance with US
      recommendations for immunization against influenza in pregnancy is poor.
      Polysaccharide vaccines against Haemophilus influenzae type b, Streptococcus
      pneumoniae and Neisseria meningitidis are safe and immunogenic in pregnancy.
      Protein conjugate vaccines against these infections would be likely to induce
      higher maternal antibody levels and improve placental transport, thereby further
      reducing the maternal and infant disease burden. Further studies of acellular
      pertussis vaccines for use in adolescents and adults should evaluate if maternal
      immunization could prevent life-threatening pertussis in young infants. Maternal
      immunization against group B streptococcus is projected to be superior to
      screening and/or chemoprophylaxis strategies in decreasing infant disease.
      SUMMARY: Maternal immunization, with the passage of protective antibody to
      infants, is a potential strategy to prevent infection in infants who have not
      completed their primary immunization series from both specific infections of
      infancy and vaccine-preventable illnesses. Further evaluation of this strategy is
      supported by medical literature, but liability and educational barriers exist.

PMID- 16645490
TI  - Probiotics and neonatal intestinal infection.
AB  - PURPOSE OF REVIEW: Necrotizing enterocolitis remains an enigmatic and potentially
      devastating condition with high morbidity and mortality. This review explores
      ways in which bacterial pathogens, together with gut microflora, influence the
      pathophysiology of necrotizing enterocolitis. Specifically, it examines the role
      of gut microbial colonization and its 'normalization' with probiotics vis a vis
      its contribution to intestinal bacterial invasion. RECENT FINDINGS: Recent
      studies have demonstrated that prophylactic administration of probiotics to
      preterm neonates decreases both the incidence and severity of subsequent
      necrotizing enterocolitis. SUMMARY: Probiotics represent a therapeutic effort to
      bolster natural host defenses via the 'normalization' of abnormal gut microflora
      of the premature infant at risk, thereby reducing the subsequent threat of
      necrotizing enterocolitis. The appeal of probiotics in neonatology is threefold.
      First, their safety record renders them an attractive alternative to many of the
      more aggressive therapeutic options; second, they represent a simple, noninvasive
      attempt to recreate a natural or normal flora rather than a disruption of nature.
      Third, probiotics are used mainly for disease prevention and are naturally
      occurring. As such, they are not considered to be drugs, but rather food
      supplements. To date, very few other strategies have been proven definitively to
      be efficacious in decreasing the incidence of necrotizing enterocolitis.

PMID- 16645491
TI  - The significance of Ureaplasma urealyticum as a pathogenic agent in the
      paediatric population.
AB  - PURPOSE OF REVIEW: Ureaplasma urealyticum is a frequent commensal in the lower
      genital tract of sexually active women. It may be transmitted perinatally from
      the colonized mother to her offspring, often resulting in prematurity and
      neonatal disease. The microorganism also sustains a causative role for infectious
      diseases in older children. RECENT FINDINGS: U. urealyticum infection can be
      diagnosed by culture, polymerase chain reaction, and the detection of specific
      antibodies. Neonatal infection has been implicated in various pathological
      conditions including pneumonia, chronic lung disease, central nervous system
      disorders, sepsis, osteomyelitis and even death. Older children may present with
      wheezing, pneumonitis, pertussis-like syndrome and different forms of arthritis.
      Large well-designed trials have demonstrated that the regular administration of
      antibiotics to vaginally colonized women are not beneficial in terms of
      preventing preterm labour. Macrolide-containing antibiotic regimens are, however,
      recommended for preterm premature rupture of the membranes. Erythromycin
      treatment of ureaplasma respiratory colonized premature infants shows no
      reduction in the incidence of chronic lung disease. Treatment of central nervous
      system infections, sepsis and arthritides includes tetracyclines,
      fluoroquinolones and anti-inflammatory agents, respectively. SUMMARY: This review
      covers recent evidence concerning the role of U. urealyticum as a pathogen during
      childhood. It also includes an evaluation of contemporary diagnostic techniques
      and optimal therapeutic approaches.

PMID- 16645493
TI  - Bibliography. Current world literature. Pathogenesis and immune response.

PMID- 16645492
TI  - Neonatal infection and long-term neurodevelopmental outcome in the preterm
      infant.
AB  - PURPOSE OF REVIEW: The relationship between infection, the inflammatory response
      and adverse neurodevelopmental outcome in preterm infants is slowly being
      elucidated. The developing brain, particularly the periventricular white matter,
      is vulnerable to cytotoxic and hypoxic/ischemic injury, which places these
      infants at increased risk for abnormal cognitive and motor functioning. This
      review summarizes current data evaluating associations between infection and
      neurodevelopmental outcome in the preterm infant. RECENT FINDINGS: Preterm
      infants are at risk for intrauterine and postnatal infections. Recent studies
      have linked infection/inflammation associated with chorioamnionitis, sepsis and
      necrotizing enterocolitis with adverse neurodevelopmental outcome and impaired
      growth in preterm infants. Investigators have also shown associations between
      infection and brain injury, including severe intraventricular hemorrhage and
      periventricular leukomalacia. Very-low-birth-weight preterm infants are at
      substantial risk for neonatal infection, with associated morbidity and mortality.
      It is postulated that exposure of the preterm brain to inflammatory mediators
      during infectious episodes contributes to brain injury and poor developmental
      outcome. SUMMARY: Enhanced understanding of the interaction of infection,
      inflammation and brain injury will be critical to developing strategies to
      improve neurodevelopmental outcome in preterm infants.

PMID- 16645494
TI  - Staying alert about NAPS.

PMID- 16645497
TI  - Carotid artery stenting: new hope for blocked vessels.

PMID- 16645498
TI  - What's causing your patient's chest pain?

PMID- 16645499
TI  - Knowledge and practices relating to the 2004 acute otitis media clinical practice
      guideline: a survey of practicing physicians.
AB  - OBJECTIVE: To identify primary care physicians' familiarity with the 2004 acute
      otitis media (AOM) clinical practice guideline and to compare their practices
      with its recommendations. DESIGN: Mail survey October through December 2004 to
      all active physician members of the Slone Center Office-based Research Network, a
      national, practice-based, pediatric research network. RESULTS: The response rate
      was 276 of 469 (58.8%). Overall, 90.5% had read the guideline or summaries of it.
      Pneumatic otoscopy was always used by 16.2%, used half the time or more by 23.1%,
      used less than half the time by 34.6% and never used by 26.2%. Observation is
      considered a reasonable option for some AOM cases by 88.0% and, over the previous
      3 months, these physicians used observation a median of 10% of the time (25th and
      75th percentiles, 5% and 25%, respectively). In terms of concern that the
      observation option may increase AOM complications, 75.6% were not at all or only
      slightly concerned; 24.4% were moderately or very concerned. In general, these
      physicians have altered their antibiotic prescribing practices for AOM towards
      the guideline's recommendations since its publication. However, antibiotic
      choices deviated most widely from the guideline in cases of AOM with severe
      illness, where only 17.9% follow the recommendation for high-dose amoxicillin
      clavulanate, and in cases of children who fail treatment with amoxicillin
      clavulanate, where only 27.7% favor the recommended intramuscular ceftriaxone.
      CONCLUSIONS: Most physicians in this survey are familiar with the AOM guideline,
      but many do not follow its diagnostic and antibiotic recommendations. Observation
      for selected cases is acceptable to most of these physicians and is currently
      used in a small proportion of cases.

PMID- 16645500
TI  - SEN virus infection in children in Taiwan: transmission route and role in blood
      transfusion and liver diseases.
AB  - BACKGROUND: SEN virus (SENV) is a newly discovered DNA virus. We conducted this
      study to evaluate potential modes of SENV transmission and the pathogenic effect
      of SENV on liver diseases in children. METHODS: Polymerase chain reaction was
      used to detect 2 SENV variant (SENV-D and SENV-H) DNA in sera from healthy
      individuals and diseased children. Nucleotide sequence of SENV was determined by
      direct sequencing. RESULTS: SENV infection was assessed in healthy individuals,
      including 50 newborns (sera collected from the umbilical cord), 24 infants, 46
      preschool children (aged 1-6 years), 42 school children of an age before that of
      the first sexual experience (aged 7-12 years), 62 adolescents (13-18 years), 72
      young adults (19-30 years) and 32 adults (>30 years). The prevalence of SENV-D
      and/or SENV-H (SENV-D/H) viremia in each group was 0%, 17%, 24%, 24%, 27%, 33%
      and 40%, respectively. The prevalence of SENV-D/H viremia in 18 children with non
      A to E hepatitis, 64 thalassemic children, 80 children transfused during cardiac
      surgery, 30 children with chronic hepatitis B, 9 children with chronic hepatitis
      C and 32 infants with biliary atresia was 11%, 61%, 80%, 83%, 67% and 50%,
      respectively. SENV was found more frequently in all patient groups than in 174
      age-matched controls (P < 0.01), with the exception of non-A to E hepatitis (11%
      versus 24% in the control group; P = 0.27). In 2 infants with proven intrauterine
      hepatitis B viral infection, identical SENV-D nucleotide sequence existed in both
      the maternal and neonate serum. Elevated alanine aminotransferase concentrations
      were rarely observed in children who acquired isolated SENV viremia because of
      transfusion for surgery. Infection with SENV in children with chronic hepatitis C
      virus or hepatitis B viral infection was not associated with higher peak alanine
      aminotransferase values. CONCLUSION: SENV is transmitted mainly via nonparenteral
      daily contact and frequently occurs early in life. Transfusion can significantly
      increase the rate of SENV viremia. SENV does not appear to cause hepatitis in
      children.

PMID- 16645501
TI  - Multistate surveillance for laboratory-confirmed, influenza-associated
      hospitalizations in children: 2003-2004.
AB  - BACKGROUND: Increasing use of rapid influenza diagnostics facilitates laboratory
      confirmation of influenza infections. We describe laboratory-confirmed, influenza
      associated hospitalizations in a population representing almost 6% of children in
      the United States. METHODS: We conducted population-based surveillance for
      influenza-associated hospitalizations between October 1, 2003, and March 31,
      2004, in 54 counties in 9 states (4.2 million children) participating in the
      Emerging Infections Program Network. Clinical characteristics, predictors of
      intensive care unit admission and geographic and age-specific incidence were
      evaluated. RESULTS: Surveillance identified 1,308 case-patients; 80% were <5
      years and 27% were <6 months of age. Half of the patients and 4 of 5 pediatric
      deaths did not have a medical indication for influenza vaccination and were
      outside the 6- to 23-month age group. Twenty-eight percent of case-patients had
      radiographic evidence of a pulmonary infiltrate, 11% were admitted to intensive
      care and 3% received mechanical ventilation. The median length of hospital stay
      was 2 days. Community-acquired invasive bacterial coinfections (1% of patients)
      were associated with intensive care admission (adjusted odds ratio, 16.9; 95%
      confidence interval, 5.0-56.8). Thirty-five percent of patients >or=6 months old
      had received at least one influenza vaccine dose that season. The overall
      incidence of influenza-associated hospitalizations was 36 per 100,000 children
      (range per state, 10 per 100,000 to 86 per 100,000). CONCLUSIONS: Influenza was
      an important cause of hospitalizations in children during 2003-2004.
      Hospitalizations were particularly common among children <6 months of age, a
      group for whom influenza vaccine is not licensed. Continued surveillance for
      laboratory-confirmed influenza could inform prevention strategies.

PMID- 16645502
TI  - Effectiveness of inactivated influenza vaccine for prevention of otitis media in
      children.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness of
      inactivated influenza vaccine in preventing acute otitis media (AOM) and otitis
      media with effusion (OME) in children aged 6 to 60 months who attend day care.
      STUDY DESIGN: This prospective, single-blind study was conducted in 8 day care
      centers in Ankara, Turkey. One hundred nineteen (61 vaccinated and 58
      unvaccinated against influenza) healthy children were examined at study entry and
      at 6-week intervals for 6 months by the same 2 otorhinolaryngologists who were
      blinded about the vaccination status of the children. The frequency of AOM and
      OME is compared between the 2 groups and the effect of influenza season on
      frequency of episodes was evaluated. Based on national influenza laboratory data,
      the influenza season was determined to be the period between December 15, 2003,
      and January 31, 2004. RESULT: The frequencies of AOM, OME and total otitis media
      episodes in vaccinated children were 2.3%, 22.8% and 25.2%, respectively, and
      these frequencies were 5.2%, 31.1% and 36.3% in the unvaccinated group. The
      difference was statistically significant (P < 0.01). This difference was
      especially prominent in the influenza season (P < 0.05). CONCLUSION: Influenza
      vaccine is effective in reducing AOM and OME episodes in 6- to 60-month-old day
      care children, especially during influenza season.

PMID- 16645503
TI  - Pharmacokinetics of rifapentine in children.
AB  - BACKGROUND: Rifapentine is a rifamycin antibiotic approved for the treatment of
      pulmonary infections caused by Mycobacterium tuberculosis. Although the
      pharmacokinetics of rifapentine has been investigated in adolescents and adults,
      no studies have assessed the pharmacokinetics of this drug in children or
      infants. METHODS: Twenty-four children (7.1 +/- 3.3 years; mean +/- 1 SD, 27.9 +/
      11.9 kg) were enrolled in this open label study. Children received a single oral
      dose (10 to <30 kg body weight received 150 mg; 30 to <60 kg body weight received
      300 mg), followed by repeated blood sampling (n = 11) for 32 hours. Rifapentine
      and 25-desacetyl rifapentine were quantitated by a validated high-pressure liquid
      chromatography method. Pharmacokinetic parameters were determined using a model
      independent approach. RESULTS: A significant difference in dose-normalized area
      under the curves (AUC0-n and AUC0-infinity) was observed between children
      receiving the 150 and 300 mg doses, which was accounted for by differences in age
      between the dosing arms. In separate analyses, including data from adults,
      further age-dependence in total body exposure (reflected by AUC) and elimination
      was observed. Adverse events associated with rifapentine were mild and included
      gastric distress (n = 1) and vomiting (n = 2). CONCLUSIONS: Given a comparable
      weight-normalized dose, rifapentine exposure estimates are lower in children than
      those reported in adults, suggesting that a larger weight-normalized (ie, mg/kg)
      dose of rifapentine is needed in children.

PMID- 16645504
TI  - T280M variation of the CX3C receptor gene is associated with increased risk for
      severe respiratory syncytial virus bronchiolitis.
AB  - BACKGROUND: Recent data suggest that immunologic response during respiratory
      syncytial virus (RSV) infection is partially modified through interaction of
      viral G glycoprotein with the host's chemokine receptor, CX3CR1. We hypothesized
      that two nonsynonymous, single-nucleotide polymorphisms of the CX3CR1 gene
      (CX3CR1-V249I and CX3CR1-T280M) that disrupt the affinity of CX3CR1 for its
      natural ligand (fractalkine) could also affect the G glycoprotein-CX3CR1 pathway.
      METHODS: To test the hypothesis, DNA samples were obtained from 82 children
      hospitalized for RSV bronchiolitis in a 1-year period. One hundred twenty sex
      matched healthy adults, without a history of severe lower respiratory tract
      infections, formed the control group. RESULTS: Epidemiologic data showed an
      increase in the RSV infection rate during the late winter season, with a peak
      rate in early spring. Genotyping revealed predominance of the 280M-containing
      genotypes (M/M or T/M) in cases compared with controls (37.8% versus 20.8%,
      respectively; odds ratio, 2.03; 95% confidence interval, 1.1-3.9; P = 0.025),
      demonstrating an association between the common CX3CR1-T280M variations and
      increased risk of severe RSV bronchiolitis. CONCLUSIONS: Our findings support the
      hypothesis of the pivotal role of the G glycoprotein CX3CR1 pathway in the
      pathogenesis of RSV bronchiolitis and propose CX3CR1 as a potential therapeutic
      target.

PMID- 16645505
TI  - The epidemiology of Haemophilus influenzae type b meningitis in Burkina Faso.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) disease burden studies are
      important to conduct in African countries that plan to introduce vaccine so that
      vaccine impact can be documented. METHODS: We implemented population-based
      meningitis surveillance in 3 districts of Burkina Faso for 12 months each during
      2002-2003 and 2004-2005 using polymerase chain reaction, culture and antigen
      detection. RESULTS: Lumbar puncture was performed on 1686 patients and 112 had
      Hib identified. Persons <1, <5, 5-14 and 15+ years of age had annual Hib
      meningitis incidences of 97, 34, 2.1 and 0.55 per 100,000, respectively; overall
      case fatality proportion was 25%. During the historic meningitis epidemic season
      months of December through April, the proportion of purulent cerebrospinal fluid
      among children aged <5 years that yielded Hib was 27% compared with 30% during
      other months. Twenty-five of 98 persons with information available were treated
      with only one or 2 doses of oily chloramphenicol. Among children age <5 years
      with Hib meningitis, 28% were pretreated with antimalarials and antimalarial
      pretreatment was associated with delay in hospitalization. CONCLUSIONS: In
      Burkina Faso, Hib meningitis incidence and case fatality proportion are high and
      thus vaccine could have a substantial impact. While awaiting well-implemented
      routine infant Hib vaccination, empiric case management for pediatric meningitis
      in sub-Saharan Africa must recognize that Hib is likely even during the epidemic
      season. In malaria-endemic areas, pediatric Hib meningitis case management may be
      adversely affected by the similar presentation of these 2 diseases.

PMID- 16645506
TI  - Outcomes for human immunodeficiency virus-1-infected infants in the United
      kingdom and Republic of Ireland in the era of effective antiretroviral therapy.
AB  - BACKGROUND: There are few data about disease progression and response to
      antiretroviral therapy (ART) in vertically HIV-infected infants in the era of
      effective therapy. DESIGN: Cohort study. METHODS: We examined progression to
      acquired immunodeficiency syndrome (AIDS) and death over calendar time for
      infants reported to the National Study of HIV in Pregnancy and Childhood in the
      United Kingdom/Ireland. The use of ART and CD4 and HIV-1 RNA responses were
      assessed in a subset in the Collaborative HIV Pediatric Study. RESULTS: Among 481
      infants, mortality was lower in those born after 1997 (HR 0.30; P < 0.001), with
      no significant change in progression to AIDS. Of 174 infants born since 1997 in
      the Collaborative HIV Pediatric Study, 41 (24%) were followed from birth, 77
      (44%) presented pre-AIDS and 56 (32%) presented with AIDS. Of 125 (72%) children
      on 3- or 4-drug ART by the age of 2 years, 59% had HIV-1 RNA <400 at 12 months;
      median CD4 percentage increased from 24% to 35%. Among 41 infants followed from
      birth, 12 progressed to AIDS (5 while ART naive) and 3 died; 1 of 10 infants
      initiating ART before 3 months of age progressed clinically. CONCLUSION:
      Mortality in HIV-infected infants is significantly lower in the era of effective
      ART, but symptomatic disease rates remain high. Infrequent clinic attendance and
      poor compliance with cotrimoxazole prophylaxis and/or ART in infants born to
      diagnosed HIV-infected women and late presentation of infants identified after
      birth appear to be major contributors. Poor virologic response to ART during
      infancy is of concern because of increased likelihood of early development of
      resistance.

PMID- 16645507
TI  - Detection of lipoatrophy in human immunodeficiency virus-1-infected children
      treated with highly active antiretroviral therapy.
AB  - BACKGROUND: Highly active antiretroviral therapy has been associated with
      lipodystrophy in adults. Much is unknown about its characteristics, especially in
      children. OBJECTIVE: To obtain an objective case definition of the lipodystrophy
      syndrome. METHODS: This was a cross-sectional study. One investigator rated
      clinical lipodystrophy. Body composition was measured using body mass index, skin
      fold thickness and circumference of arm, leg, waist and hip. Samples for human
      immunodeficiency virus (HIV)-1 RNA, CD4 cell count, fasting lipids and glucose
      variables were drawn. HIV-infected children with lipodystrophy were compared with
      HIV-infected children without lipodystrophy (controls). RESULTS: Thirty-four
      children were included: 28 controls, 2 nonassigned, and 4 with the lipoatrophic
      phenotype. Lipohypertrophy or mixed syndrome were not observed. All children with
      lipoatrophy were pubertal; they had used stavudine and didanosine longer.
      Children with lipoatrophy had significantly smaller arm and leg circumference,
      and their skin folds were thinner. The torso-to-arm ratio was 3 times higher in
      lipoatrophic children, but the difference did not reach significance. The waist
      to-hip ratio was higher (P = 0.005). None of the laboratory values differed
      significantly between the two groups, but all children with lipoatrophy had an
      increased C-peptide level above the upper limit of normal. All children with
      lipoatrophy could be distinguised from controls by an increased C-peptide level,
      a waist-to-hip ratio z score of 1 standard deviation or higher and a sum of skin
      folds z score below -1 standard deviation. CONCLUSIONS: All children with
      lipoatrophy can be distinguished by using anthropometric measurements and C
      peptide measurement in serum. This method is simple, readily available and
      inexpensive.

PMID- 16645508
TI  - Psychiatric disorders in youth with perinatally acquired human immunodeficiency
      virus infection.
AB  - BACKGROUND: Clinical reports from the United States indicate substantive mental
      health problems in perinatally human immunodeficiency virus (HIV)-infected youth
      that pose substantial barriers to optimizing their health. This pilot study
      explores rates and types of psychiatric and substance use disorders, as well as
      emotional and behavioral functioning in perinatally HIV-infected children and
      adolescents. METHODS: Forty-seven perinatally-infected youths (9-16 years of age)
      and their primary caregivers recruited from a pediatric HIV clinic were
      interviewed using standardized assessments of youth psychiatric disorders and
      emotional and behavioral functioning, as well as measures of health and caregiver
      mental health. RESULTS: According to either the caregiver or child report, 55% of
      youths met criteria for a psychiatric disorder. The most prevalent diagnoses were
      anxiety disorders (40%), attention deficit hyperactivity disorders (21%), conduct
      disorders (13%), and oppositional defiant disorders (11%). However, the majority
      of caregivers and children scored in the normative range on the symptom
      questionnaires on emotional and behavioral functioning. None of the demographic
      or child health variables or measures of caregiver mental health was
      significantly associated with presence of a child psychiatric disorder. There was
      an association between caregiver mental health and child emotional and behavioral
      functioning. CONCLUSIONS: Standardized assessments of mental health identified
      very high rates of psychiatric disorders, primarily in the anxiety and behavioral
      domains, in this sample of youth with perinatal HIV infection. Mental health
      interventions should be integrated into medical care to help members of this
      highly vulnerable population optimize their health and well-being.

PMID- 16645509
TI  - Risk factors for developing nosocomial infections among pediatric patients.
AB  - BACKGROUND: Nosocomial infections (NIs) are important causes of morbidity and
      mortality in pediatric hospitals. Multiple factors contribute towards exposing
      children to the risk of infection when hospitalized, and some of them differ from
      those in adults. METHODS: This was a prospective study in a tertiary-level
      teaching pediatric hospital in Salvador, Bahia, Brazil, conducted from January to
      July, 2003, to describe the epidemiologic characteristics of NIs. Centers for
      Disease Control's standard definitions were used and the data recorded included
      intrinsic and extrinsic risk factors. RESULTS: We evaluated 808 patients. There
      were 143 episodes of NI in 124 patients (15.4%). The overall incidence of NI
      cases was 9.2 per 1,000 patient-days, with higher rates among children aged less
      than 1 year (P < 0.001) and those with nonsurgical clinical diseases (P < 0.001).
      Gastrointestinal infections (39.2%) and eye, ear, nose, throat or mouth
      infections (29.4%) were most common. The factors most closely associated with
      higher incidence of NI were respiratory disease on admission (incidence density
      ratio [IDR], 4.0; 95% confidence interval [CI], 2.83-5.72), another disease
      associated with admission diagnosis (IDR, 3.5; 95% CI, 2.41-5.02), nonsurgical
      clinical disease (IDR, 5.9; 95% CI, 3.92-8.85) and pediatric intensive care unit
      residence (IDR, 3.5; 95% CI, 1.91-6.28). The lengths of hospital stay for
      patients with and without nosocomial infection were, respectively, 14.1 days (SD,
      20.5 days) and 5.1 days (SD, 6.6 days) (t = 121.76; P < 0.001). CONCLUSIONS:
      Nosocomial infections are a frequent complication in pediatrics. They are not
      necessarily related to invasive procedures but certainly are related to a group
      of factors that have particular characteristics in the pediatric age group.

PMID- 16645510
TI  - Parainfluenza viruses: an underappreciated cause of pediatric respiratory
      morbidity.

PMID- 16645511
TI  - Antibiotic lock technique to reduce central venous catheter-related bacteremia.

PMID- 16645512
TI  - Temporal and geographic trends of rotavirus activity in the United States, 1997
      2004.
AB  - Rotavirus (RV) has a characteristic seasonal pattern in the 48 contiguous states
      of the continental United States, and climatologic factors have been implicated
      though not confirmed. Since 1997, three significant events occurred, including
      strong El Nino and La Nina climatologic phenomena, and the brief introduction of
      a rotavirus (RV) vaccine. We examined trends in RV activity in the continental
      United States between 1997 and 2004, using data from a network of over 70
      laboratories that voluntarily report weekly RV detection rates within the
      National Respiratory and Enteric Virus Surveillance System (NREVSS). Analysis of
      NREVSS data indicates characteristic winter activity that begins in the Southwest
      in December or January, moves across the country, and ends in the Northeast in
      April or May. This pattern was not affected by the brief use of RV vaccine nor by
      periods of climate change associated with the El Nino and La Nina phenomena. The
      temporal and geographic pattern of RV spread in the United States has persisted
      since its initial description and defies easy explanation. An impact of the RV
      vaccine was not observed, either because of the limited uptake of the vaccine or
      the inherent variability of the system. NRVESS permits a gross assessment of RV
      geographic and temporal trends in the United States, but underscores the need for
      additional assessment mechanisms.

PMID- 16645513
TI  - Invasive pneumococcal disease burden in Hong Kong children.
AB  - In a retrospective, population-based study, we estimated the age-specific
      incidence of invasive pneumococcal disease in Hong Kong between 1995 and 2004.
      The incidence rates per 100,000 were 18.3 (95% confidence interval [CI], 13.9
      23.3) for children aged <or=2 years, 15.6 (95% CI, 12.8-18.6) for children aged
      <or=5 years and 1 (95% CI, 0.52-1.7) for children aged 6-14 years. The findings
      indicate a significant disease burden.

PMID- 16645514
TI  - Rotavirus gastroenteritis among children under five years of age in Valencia,
      Spain.
AB  - The population-based incidence of rotavirus gastroenteritis in children <5 years
      of age in Valencia, Spain, over a 1-year period (December 1, 2003, to November
      30, 2004) was determined.A total of 553 episodes of gastroenteritis in children
      <5 years of age (mean age, 22.8 +/- 14.5 months) were recorded (annual incidence
      of 138 per 1,000). A positive enzyme-linked immunoadsorbant assay result for
      rotavirus antigen was obtained in 15% of the samples. The incidence of rotavirus
      gastroenteritis was 15 per 1,000 children <5 years of age, being the highest
      incidence in children <or=12 months of age (31 per 1,000). Eighty percent of
      rotavirus gastroenteritis occurred during the winter months (January-March).
      Genotype G1 was detected in 86% of the samples and G4 in the other 14%.

PMID- 16645515
TI  - Complex clonal features in an mycobacterium tuberculosis infection in a two-year
      old child.
AB  - The focus of this report is to describe the highly complex clonal features of the
      Mycobacterium tuberculosis (MTB) isolates cultured from a 2-year-old child with
      no risk factors for tuberculosis. Molecular analysis showed that she was
      coinfected by 2 MTB isolates. The coinfecting isolates showed only subtle genetic
      differences and shared equivalent infectivity in vitro; however, they were
      infecting independent anatomic sites (compartmentalized infection). One of the
      MTB isolates was cultured only from respiratory specimens, whereas the other was
      isolated from extrarespiratory site (central nervous system).

PMID- 16645516
TI  - Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in
      patients admitted to Driscoll Children's Hospital.
AB  - A nasal swab specimen was collected for culture within 48 hours of admission and
      a questionnaire was completed using a convenience sample of 350 patients admitted
      to Driscoll Children's Hospital between February 15 and March 15, 2005. Of the
      350 patients enrolled, 125 (36%) patients were colonized with Staphylococcus.
      aureus and 76 (61%) of the 125 S. aureus isolates were methicillin-resistant.

PMID- 16645517
TI  - The use of combination subtyping in the forensic evaluation of a three-year-old
      girl with gonorrhea.
AB  - The use of pulsed field gel electrophoresis and neisserial lipoprotein gene
      sequencing for subtyping Neisseria gonorrhoeae has not been reported in the
      evaluation of sexually abused children. We report the application and
      implications of combining pulsed field gel electrophoresis and lipoprotein
      subtyping in the evaluation of a 3-year-old girl with N. gonorrhoeae infection.

PMID- 16645518
TI  - Recurrent aseptic encephalitis in periodic fever, aphthous stomatitis,
      pharyngitis and adenopathy (PFAPA) syndrome.
AB  - An 11-year-old boy with episodes of periodic fever, aphthous stomatitis,
      pharyngitis and adenitis (PFAPA) is reported. Two PFAPA episodes were associated
      with aseptic encephalitis and seizures. Recurrent acute aseptic encephalitis or
      seizures have never been reported during the febrile episodes of PFAPA. This
      possible association is discussed within the context of the etiology of PFAPA.

PMID- 16645519
TI  - Primary intestinal aspergillosis after high-dose chemotherapy and autologous stem
      cell rescue.
AB  - Primary invasive aspergillosis of the gut is a rare event and is associated with
      high mortality. We report for the first time on a patient who had isolated
      aspergillosis of the small bowel after autologous stem cell transplantation.
      Diagnosis of invasive aspergillosis of the gut was based on abdominal pain,
      galactomannan antigenemia and isolation of Aspergillus fumigatus from the stool
      and was later confirmed by pathohistologic examination. No other site of invasive
      aspergillosis was evident. The patient was successfully treated with early
      surgery and combination antifungal therapy.

PMID- 16645520
TI  - Mazzotti reaction after presumptive treatment for schistosomiasis and
      strongyloidiasis in a Liberian refugee.
AB  - We report a case of the Mazzotti reaction in a 13-year-old Liberian refugee after
      presumptive treatment of schistosomiasis and strongyloidiasis with ivermectin,
      praziquantel and albendazole. The patient was hospitalized with fever, urticaria,
      abdominal pain and angioedema. Twelve hours after treatment with intravenous
      methylprednisolone he had complete resolution of his symptoms.

PMID- 16645521
TI  - Lower extremity furunculosis in a female adolescent.

PMID- 16645522
TI  - Simkania negevensis and pneumonia in children.

PMID- 16645523
TI  - Fungal resistance in Cambodian children with acquired immunodeficiency syndrome.

PMID- 16645525
TI  - Doctor, can you order that menopause test?

PMID- 16645526
TI  - Hormone therapy and breast cancer risk: trumping fear with facts.

PMID- 16645527
TI  - Black cohosh: will there ever be an answer or answers?

PMID- 16645528
TI  - Progesterone: a "weight watcher's pill" for reproductively aging women.

PMID- 16645529
TI  - Androgens and menopause: more fuel for the fire.

PMID- 16645530
TI  - Limitations of follicle-stimulating hormone in assessing menopause status:
      findings from the National Health and Nutrition Examination Survey (NHANES 1999
      2000)*.
AB  - OBJECTIVE: We used data from the National Health and Nutrition Examination Survey
      (NHANES 1999-2000) to: establish new population-based estimates for follicle
      stimulating hormone (FSH) and luteinizing hormone (LH); identify factors
      associated with FSH; and assess its efficacy in distinguishing among women in the
      reproductive, menopause transition, and postmenopausal stages. DESIGN: Nationally
      representative sample of 576 women aged 35 to 60 years examined during NHANES
      1999-2000. RESULTS: Levels of FSH and LH increased significantly with
      reproductive stage. (Geometric mean FSH levels for successive stages:
      reproductive, 7.0 mIU/mL, SE 0.4; menopause transition, 21.9 mIU/mL, SE 3.7; and
      postmenopause, 45.7 mIU/mL, SE 4.3). There was considerable overlap, however,
      among distributions of FSH by stage. Only age and reproductive stage were
      significantly associated with FSH in multivariable analysis. FSH cutoff points
      between the reproductive and menopause transition stages [FSH = 13 mIU/mL,
      sensitivity 67.4% (95% CI 50.0-81.1), specificity 88.1% (95% CI 81.1-92.8)] and
      between the menopause transition and postmenopause stages [FSH = 45 mIU/mL,
      sensitivity 73.6% (95% CI 60.1-83.7), specificity 70.6% (95% CI 52.4-84.0)] were
      neither sensitive nor very specific. CONCLUSIONS: Age and reproductive stage are
      the most important determinants of FSH levels in US women; however, FSH by itself
      has limited utility in distinguishing among women in different reproductive
      stages.

PMID- 16645531
TI  - Hormone therapy and breast cancer: what factors modify the association?
AB  - OBJECTIVE: To determine factors that may modify the association between hormone
      therapy (HT) and breast cancer risk. DESIGN: Prospective cohort study (the
      Melbourne Collaborative Cohort Study) of 24,479 women aged 40 to 69 years.
      History of HT use was collected at baseline and 4 years later by questionnaire.
      By June 2002, 336 cases of breast cancer were diagnosed among 13,444 women
      postmenopausal at baseline. Association of breast cancer risk with history of HT
      use was analyzed using proportional hazards models. RESULTS: The hazard ratio
      (HR) for recent HT use (current or stopped within the last year) was elevated (HR
      1.51; 95% CI, 1.16-1.98) but was not significantly increased for past HT users
      (HR 1.19; 95% CI, 0.86-1.64). Recent HT use was associated with better
      differentiated tumors but was not more likely to be associated with estrogen
      receptor-positive / progesterone receptor-positive tumors. There was little
      evidence of interactions between recent HT use and body mass index, alcohol
      intake, parity, and smoking, although the HR for recent HT use in categories of
      alcohol consumption was greatest in women consuming the most alcohol (HR 2.37;
      95% CI, 1.45-3.88 for those consuming > or = 10 g/d versus HR 1.33; 95% CI, 0.85
      2.08 for nondrinkers, P interaction = 0.32). CONCLUSIONS: The risk of breast
      cancer for recent users of HT in this Australian population is increased by
      approximately 50%. Our results suggest that any potential modifying effect of the
      association between HT and breast cancer risk by factors such as alcohol intake
      and body mass index is likely to be modest.

PMID- 16645532
TI  - Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa,
      and various blood parameters in postmenopausal women: a double-blind, placebo
      controlled, and conjugated estrogens-controlled study.
AB  - OBJECTIVES: In this study, the effects of the Cimicifuga racemosa (CR)
      preparation CR BNO 1055 on markers of bone metabolism, hormones, sex hormone
      binding globulin (SHBG), lipometabolism, vaginal maturity, and routine laboratory
      parameters were compared with those of conjugated estrogens (CE) and placebo.
      DESIGN: Sixty-two postmenopausal women were included in this double-blind study.
      Treatment duration with CR (daily dose corresponds to 40 mg of herbal drug), CE
      (0.6 mg/day), or placebo was 12 weeks. Markers of bone turnover (bone-specific
      alkaline phosphatase, CrossLaps), estradiol, follicle-stimulating hormone,
      leuteinizing hormone, SHBG, triglycerides, total cholesterol, high-density
      cholesterol, low-density cholesterol, and routine clinical chemistry parameters
      were determined from blood samples. Vaginal "maturity index" was determined from
      vaginal smears. RESULTS: The analyses of bone turnover markers indicated
      beneficial effects for CR and CE on bone metabolism. CR stimulated osteoblast
      activity, whereas CE inhibited osteoclast activity. Whereas CE showed strong
      estrogenic effects on vaginal mucosa, CR showed weak estrogen-like activity. No
      significant effects were seen on coagulation markers and liver enzymes in the
      blood. CR was well tolerated. CONCLUSION: These results suggest that CR has
      beneficial bone remodeling and weak estrogen-like effects in the vaginal mucosa.

PMID- 16645533
TI  - Cyclic progestin administration increases energy expenditure and decreases body
      fat mass in perimenopausal women.
AB  - OBJECTIVE: The menopause transition is characterized by luteal phase defect
      anovulatory cycles, and changes in body weight and body composition. Resting
      metabolic rate (RMR) is increased in the luteal phase of the menstrual cycle. We
      evaluated whether progestin administration increases RMR and influences body
      composition of perimenopausal women. DESIGN: Thirty-six perimenopausal women were
      randomly allocated to receive either calcium (1 g/day) continuously plus the
      progestin nomegestrol acetate (NOMAc; 5 mg/day for 10 days x month for 12 months)
      or calcium alone. Body composition, RMR, energy intake, and climacteric and
      psychological symptoms were evaluated at baseline and after 12 months. In the
      NOMAc group, body composition and RMR analyses were performed twice during the
      first month of treatment. One evaluation was performed after almost 8 days of
      NOMAc adjunct, and an another before or almost 15 days after NOMAc
      administration. RESULTS: Resting metabolic rate was increased by NOMAc
      administration of 54.5 +/- 73.8 kcal/24 h (P < 0.01). In women treated with
      NOMAc, fat mass decreased by 1.2 +/- 0.6 kg (P < 0.001). In comparison with
      controls, body weight (P < 0.05) and body mass index (P < 0.05) were also reduced
      after 12 months of therapy with NOMAc. CONCLUSIONS: In perimenopausal women the
      use of NOMAc increases RMR. During the menopause transition, cyclic NOMAc
      administration may contribute to reduce negative modification of body
      composition.

PMID- 16645534
TI  - Efficacy of hormone therapy with and without methyltestosterone augmentation of
      venlafaxine in the treatment of postmenopausal depression: a double-blind
      controlled pilot study.
AB  - OBJECTIVE: This study evaluated the augmentation of venlafaxine with hormone
      therapy in the treatment of postmenopausal depression. The hormones evaluated
      were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg)
      and methyltestosterone (2.5 mg). DESIGN: Seventy-two menopausal women (mean age:
      53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression
      Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of
      the following hormone therapy combinations, in a double-blind regimen: estrogen +
      medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen +
      medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3,
      n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks.
      Primary efficacy outcome was remission according to the MADRS, whereas secondary
      efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman
      Index, and Women's Health Questionnaire (WHQ). RESULTS: Forty-eight patients
      completed the study. All groups showed significant improvement from baseline.
      Group 3 demonstrated significant improvement on the MADRS compared with placebo
      (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83;
      15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had
      significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and
      44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI
      scores among the groups. CONCLUSIONS: Methyltestosterone 2.5 mg had the highest
      effect size compared with placebo, but the high dropout rate prevented its
      efficacy from being determined. Estrogen plus medroxyprogesterone, combined with
      methyltestosterone or otherwise, demonstrated a trend toward increased efficacy
      of venlafaxine. Further larger-scale clinical trials are needed to elucidate the
      findings of this pilot study.

PMID- 16645535
TI  - Increased urinary cortisol levels during the menopausal transition.
AB  - OBJECTIVE: To determine whether cortisol levels change prospectively during the
      menopausal transition (MT); whether these changes are associated with changes in
      the hypothalamic-pituitary-ovarian axis (follicle-stimulating hormone [FSH] and
      estrone glucuronide [E1G]), stressors, or menopause symptoms; and whether women
      who experienced a rise in cortisol levels during the transition had behavioral
      practices, stressors, vasomotor symptoms, or mood or sleep disturbances that
      affected hypothalamic-pituitary-adrenal axis function. DESIGN: One hundred sixty
      nine women in the middle or late MT or early postmenopause stages provided
      monthly urine specimens for cortisol, FSH, and E1G, and rated symptoms and stress
      levels as part of a longitudinal study of the MT. Of these women, 91 completed a
      transition to the next MT stage: from early to middle (n = 30), middle to late (n
      = 39), or late to postmenopause (n = 22) and were eligible for inclusion in the
      analyses. RESULTS: Cortisol increased from 7 to 12 months before the late MT
      stage to 7 to 12 months after onset of the late MT stage. There were no
      differences before and after the middle MT stage or the final menstrual period.
      Women with increased cortisol (>10 ng/mg creatinine) during the late MT stage had
      more severe vasomotor symptoms than those without changes, but did not differ in
      terms of age, body mass index, levels of FSH or E1G, health practices, exercise,
      mood, sleep, cognition, or stress levels. CONCLUSIONS: Cortisol levels rise with
      age, but have not been linked to stages of the MT. Increased cortisol levels
      during the late MT stage, when menstrual irregularities are greatest, suggests
      increases in adrenal androgens and intraabdominal fat with menopause, and may
      influence risk of cardiovascular disease, vasomotor symptoms, mood, cognition,
      and bone loss.

PMID- 16645536
TI  - Estradiol in micellar nanoparticles: the efficacy and safety of a novel
      transdermal drug-delivery technology in the management of moderate to severe
      vasomotor symptoms.
AB  - OBJECTIVE: To assess the efficacy and safety of topical micellar nanoparticle
      estradiol emulsion (MNPEE; Estrasorb; Novavax, Inc., Malvern, PA) in
      postmenopausal women with moderate to severe vasomotor symptoms. DESIGN: A
      multicenter, randomized, double-blind, placebo-controlled study was conducted in
      200 postmenopausal women with seven or more moderate to severe hot flushes per
      day. The study consisted of a 3-week screening period followed by a 1-week
      placebo emulsion run-in period and a 12-week active or placebo treatment period.
      Women were randomized (1:1) to receive MNPEE (3.45 g daily dose of emulsion
      containing 8.6 mg estradiol) or matching placebo emulsion. The primary efficacy
      variable was the change from baseline in the frequency of moderate and severe hot
      flushes at weeks 4 and 12. Adverse events were monitored throughout the trial.
      RESULTS: Topical micellar nanoparticle estradiol emulsion was statistically
      significantly superior to placebo emulsion in reducing the mean frequency of
      moderate to severe vasomotor symptoms by week 3 (P = 0.003), with superiority to
      placebo maintained from weeks 4 to 12 (P < 0.001). At week 12 (peak benefit),
      MNPEE reduced mean daily frequency of hot flush count by 11.1 (P < 0.001 vs
      placebo). MNPEE significantly reduced mean symptom severity from weeks 4 to 12 (P
      < 0.001) compared with placebo. At endpoint, mean serum concentrations of
      estradiol and estrone were 63 and 89 pg/mL, respectively, in the MNPEE group. The
      mean endpoint ratio of estradiol to estrone in these patients was 0.774. MNPEE
      was safe and well tolerated. CONCLUSION: Once-daily application of 3.45 g of
      micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe
      and effective in providing significant relief of vasomotor symptom frequency and
      severity in postmenopausal women.

PMID- 16645537
TI  - Effects of tibolone on estrogen biosynthesis in the mammary tissue of
      postmenopausal monkeys.
AB  - OBJECTIVE: To evaluate the long-term effects of tibolone on estrone sulfate (E1S)
      sulfatase activity in breast tissue in a primate model (Macaca fascicularis) in
      comparison with conventional hormone therapies. DESIGN: Ovariectomized female
      animals (n = 112) were randomized into five groups and treated for 2 years.
      Treatment included tibolone at 0.05 mg/kg (LoTib, n = 23) or 0.2 mg/kg (HiTib, n
      = 23), conjugated equine estrogens at 0.042 mg/kg (CEE, n = 24), CEE +
      medroxyprogesterone acetate at 0.167 mg/kg (CEE+MPA, n = 21), or placebo
      (controls, n = 21). E1S-sulfatase activity was evaluated by incubating
      homogenized breast tissue with [H]-E1S. Thin-layer chromatography was performed
      to separate the products estrone (E1) and estradiol (E2). Histomorphometry was
      performed to measure the amount of epithelial and fat tissue in the mammary
      gland. RESULTS: Significantly more E2 than E1 was produced in all groups. E1S
      sulfatase activity did not differ among the groups. E1S-sulfatase activity was
      highest in HiTib animals with less fatty breasts (5.9 fmol total estrogen/mg of
      protein/min; P < or =0.05) and lowest in HiTib animals with more fatty breasts
      (2.8 fmol total estrogen/mg of protein/min; P = 0.004 relative to less fatty
      breasts). CONCLUSIONS: We conclude that tibolone had a differential effect on
      local estrogen biosynthesis in animals with high and low breast fat content.
      Therefore, breast tissue composition affects the steroidogenic response to
      hormonal treatment.

PMID- 16645538
TI  - Prevalence of natural health product use in healthy postmenopausal women.
AB  - OBJECTIVES: Population studies examining dietary supplement use reveal that users
      are more likely to be women of older age, yet there are few focused studies among
      postmenopausal women. The purpose of this study was to determine the prevalence
      of natural health product (NHP) use, as well as the attitudes and motivations
      associated with NHP use, among postmenopausal women. DESIGN: Healthy
      postmenopausal women were recruited from shopping malls and community centers to
      complete a questionnaire that collected information regarding use of NHPs;
      attitudes and motivations about NHPs; and demographic, health, and lifestyle
      characteristics. RESULTS: The prevalence of NHP use among the 204 subjects was
      83.3%. There were no significant differences in characteristics between NHP users
      and non-users, with the exception of a lower body mass index among NHP users (P =
      0.01). The most commonly consumed NHP was calcium, followed by
      multivitamins/minerals, vitamin C, and vitamin E. Almost all NHP users (98.8%)
      believed that NHPs improved their overall health, and most (70.6%) attributed
      specific positive effects to their NHPs. Three quarters of NHP users believed
      that their NHPs could not cause adverse effects, and 64.2% believed that their
      NHPs could not interact negatively with medications. The most common source of
      NHP information was magazines/books, and 71.8% of NHP users indicated they did
      not need further information about their NHPs. CONCLUSIONS: In this study, we
      found that the prevalence of NHP use among a sample of 204 healthy postmenopausal
      women was 83.3% and that, apart from body mass index, there were no variables
      that predicted NHP use.

PMID- 16645539
TI  - Clinical studies of red clover (Trifolium pratense) dietary supplements in
      menopause: a literature review.
AB  - Red clover (Trifolium pratense L., Fabaceae) botanical dietary supplements have
      received much attention recently for their potential use in the treatment of
      menopause symptoms, maintenance/improvement of bone and cardiovascular health,
      and reported benign effects on the breast and endometrium. Literature searches of
      four computerized databases were run to identify clinical studies of red clover
      botanical dietary supplements. The manufacturer of the red clover products used
      in the majority of the studies was contacted for unpublished information and/or
      clarification regarding the chemical content of their products. Red clover
      studies were reviewed that pertained to women's health or menopause. Clinical
      evidence is presently lacking to support the efficacy of semipurified red clover
      isoflavone extracts for alleviation of climacteric vasomotor symptoms or
      reduction of low-density lipoprotein levels in the blood. Furthermore, the safety
      of use of red clover isoflavone supplements in patients with breast or
      endometrial cancer has not been established. Limited evidence suggests possible
      efficacy in maintenance of bone health and improvement of arterial compliance, a
      risk factor for atherosclerosis. This literature review covers red clover
      botanical dietary supplement clinical studies having a possible impact on the
      health care of mature and menopausal women, and provides historical perspective
      regarding the traditional uses of red clover.

PMID- 16645540
TI  - Postmenopausal status and early menopause as independent risk factors for
      cardiovascular disease: a meta-analysis.
AB  - OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous
      estrogens is suggested to enhance cardiovascular disease risk and related death
      after menopause. The aim was to obtain valid estimates of the cardiovascular
      disease risk associated with postmenopausal status and early menopause. DESIGN: A
      literature search of observational studies was performed using PubMed and EMBASE
      (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at
      menopause in relation to cardiovascular disease were selected. Six studies
      investigated menopausal status, nine studies investigated menopausal age, and
      three studied both. General variance-based methods were used to pool relative
      risk estimates and corresponding 95% confidence intervals. Stratification was
      performed for study design, type of menopause, outcome, and adjustment for age
      and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus
      premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In
      the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after
      controlling for age and smoking. The pooled effect of bilateral oophorectomy on
      cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and
      cardiovascular disease, with the menopausal age category containing 50 years as a
      reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the
      stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after
      controlling for age and smoking. The pooled effect of bilateral oophorectomy on
      cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there
      was no convincing relationship between postmenopausal status and cardiovascular
      disease. However, there was a modest effect of early menopause on cardiovascular
      disease. The effect was more pronounced for women with an artificial menopause
      than for women with a natural menopause.

PMID- 16645541
TI  - Association between menopause status and central adiposity measured at different
      cutoffs of waist circumference and waist-to-hip ratio.
AB  - OBJECTIVE: To assess the association between menopause status and central
      adiposity measured using two different cutoffs of waist circumference and waist
      to-hip ratio, while controlling for body mass index and other confounding
      factors. DESIGN: Cross-sectional study of a representative population-based
      sample of 358 women from Passo Fundo, Southern Brazil. Medical students performed
      standardized interviews and anthropometric measurements under supervision.
      Menopause status was categorized as premenopausal for those with no change in
      menstrual frequency or flow; menopause transition for those who had these
      changes; and postmenopausal after 12 months of amenorrhea or bilateral
      oophorectomy. Obesity was defined by body mass index (BMI) equal or greater than
      30 kg/m, whereas central adiposity was defined as a waist circumference equal or
      greater than 80 or 88 cm and a waist-to-hip-ratio equal or greater than 0.80 or
      0.86. RESULTS: The anthropometric assessment showed that compared with
      postmenopausal women, premenopausal women were taller, had a thinner waist
      circumference, and had a lower waist-to-hip ratio. Postmenopausal women had five
      times the chance of having central adiposity than premenopausal women, even after
      controlling for BMI and other confounding factors. Women in the menopause
      transition had an increased BMI, but there was no independent association with
      central obesity. CONCLUSION: Postmenopausal women are at greater risk of central
      adiposity as detected by both waist circumference and waist-to-hip ratio.

PMID- 16645542
TI  - Changes in serum level and metabolism of cholesterol with plant stanol esters in
      postmenopausal women with and without coronary artery disease.
AB  - OBJECTIVE: Especially in women, serum cholesterol lowering with cholesterol
      malabsorption using plant sterol ester margarine has revealed controversial
      results. Accordingly, in this retrospective study, we evaluated whether plant
      stanol (3 g/d) ester margarine consumption for 6 and 12 weeks lowers serum
      cholesterol levels in mildly hypercholesterolemic women without (n = 38) and with
      (n = 22) coronary heart disease. DESIGN: The study population was selected from
      two of our earlier studies correspondingly matched for age, body mass index, and
      serum cholesterol and triglyceride levels. In addition, the long-term effect (12
      months) of plant stanol ester with a dose reduction after 6 months (from 3-2 g
      stanol/d) was studied in the noncoronary group. RESULTS: At baseline, the
      coronary and noncoronary groups had similar serum lathosterol (synthesis marker)
      and campesterol and sitosterol (absorption markers) ratios to cholesterol, but
      high-density lipoprotein cholesterol was lower and serum squalene and desmosterol
      ratios to cholesterol were significantly higher in the coronary versus
      noncoronary groups. Short-term plant stanol ester consumption reduced serum
      cholesterol by 8.7% (P < 0.001) in the coronary group from the control margarine
      period, and in the noncoronary group by 11% from the control group (P < 0.001).
      The cholesterol-lowering effect sustained unchanged in the noncoronary subjects
      during one year consumption despite reduction of the plant stanol intake from 3
      g/d to 2 g/d. CONCLUSION: Plant stanol ester margarine consumption effectively
      reduced serum cholesterol in postmenopausal women with and without coronary
      artery disease in short-term and for at least 1 year in the noncoronary group,
      suggesting that stanol ester margarine might be used in the long-term for
      cholesterol lowering in women.

PMID- 16645543
TI  - Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative
      stress in ovariectomized rats.
AB  - OBJECTIVE: We investigated whether the effect of estrogen therapy on vascular
      endothelial function is mediated through increasing the bioavailability of
      tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized
      (Ovx) rats. DESIGN: Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy
      (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity.
      Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity,
      aortic superoxide anion (O2.), and BH4 contents were determined. RESULTS:
      Vascular reactivity, assessed on isolated aortic segments, indicated that
      phenylephrine-induced contraction in the Ovx group was significantly greater than
      that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine
      (10 to 10 M) and L-arginine (L-Arg; 10 M) in the sham and Ovx + ET groups were
      significantly greater than those in the Ovx group. Pretreatment with BH4 (10 M)
      enhanced the vasodilator responses to L-Arg in the Ovx group compared with the
      untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6
      hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L
      Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2.
      production in aortic tissues and decreased plasma NO metabolites levels, whereas
      ET significantly prevented these effects. Pretreatment with BH4 also
      significantly decreased aortic O2. production in the Ovx group; both plasma total
      antioxidant capacity and aortic BH4 contents in the Ovx group decreased
      significantly compared with those in the sham group, which were also improved by
      ET. There were no significant differences in the protein expression of
      endothelial NO synthase in aortas in these groups. CONCLUSIONS: ET increases the
      availability of vascular BH4 to attenuate O2. production and restores total
      antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.

PMID- 16645544
TI  - Differences between middle cerebral artery blood velocity waveforms of young and
      postmenopausal women.
AB  - OBJECTIVE: We characterized middle cerebral artery (MCA) blood flow velocity
      waveforms measured by transcranial Doppler ultrasonography in premenopausal (26.6
      +/- 6.1 years, mean +/- SD) and postmenopausal (54.0 +/- 3.6 years) women, of
      whom six were receiving hormone therapy (PM-HT) and seven were not (PM-non-HT).
      We hypothesized that feature points on MCA waveforms are altered in
      postmenopausal women compared with those in young women. DESIGN: A short protocol
      involved maintaining end-tidal PO2 at euoxia (88 mm Hg) and end-tidal PCO2 at 1.5
      mm Hg above eucapnic values using a dynamic end-tidal forcing system. Doppler
      data for the velocity spectral outline (Vp) were collected every 10 ms, and
      velocity waveform analyses were done on a beat-by-beat basis. Waveform features
      were identified over each cardiac cycle, including the average Vp (VCYC), maximum
      acceleration (AMAX), and the ratio of the velocity at the reflected wave and the
      velocity at peak systole (VR:VMAX). RESULTS: VCYC was unchanged between
      premenopausal and postmenopausal women (69.4 +/- 9.6 and 67.5 +/- 11.1 cm/s,
      respectively). AMAX was significantly higher (P = 0.007) in premenopausal women
      (987.9 +/- 280.7 cm/s) compared with postmenopausal women (743.1 +/- 100.3).
      Conversely, VR:VMAX was significantly smaller (P < 0.001) in premenopausal women
      (0.90 +/- 0.09) compared with postmenopausal women (1.11 +/- 0.05). In
      postmenopausal women, the reflected wave is higher than the maximum velocity at
      peak systole, suggesting the presence of a shoulder in the MCA waveform.
      CONCLUSIONS: Further investigations are required to assess whether this waveform
      analysis can provide insight into pathophysiologic changes in cerebral
      hemodynamics with aging.

PMID- 16645545
TI  - Undercarboxylated osteocalcin concentration in postmenopausal women receiving
      hormone therapy daily and on alternate days.
AB  - OBJECTIVE: Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin
      K status. The authors examined the difference in serum ucOC concentrations in
      postmenopausal women receiving hormone therapy (HT) daily and on alternate days,
      and assessed the association between ucOC and triglyceride concentrations, which
      are related to the transport of vitamin K. DESIGN: Seventy-three postmenopausal
      women were recruited for this study. Thirty-seven women received 0.625 mg of
      conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA)
      daily, and 36 women received 0.625 mg of CEE and 2.5 mg of MPA on alternate days.
      The concentrations of serum ucOC, bone turnover markers, lipid profiles, and
      hormones were measured before and after 12 months of HT. RESULTS: The ucOC
      concentration in women taking HT daily was significantly (P < 0.01) lower than
      that in women taking HT on alternate days. Serum ucOC concentrations during HT
      showed a significant (P < 0.01) inverse correlation with estradiol concentrations
      during HT. Serum estradiol concentrations during HT showed a significant (P <
      0.01) positive correlation with triglyceride concentrations during HT.
      Furthermore, ucOC concentrations during HT showed a significant (P < 0.05)
      inverse correlation with triglyceride concentrations in women receiving HT.
      CONCLUSIONS: The effect of HT on alternate days on ucOC concentration was weaker
      than the effect of HT daily. In addition, ucOC concentration after 12 months of
      HT daily might be decreased due to the conversion of ucOC to carboxylated OC by
      the effect of vitamin K through increased triglyceride levels induced by oral
      CEE.

PMID- 16645546
TI  - An increase in viral replicative capacity drives the evolution of protease
      inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs.
AB  - Little is known about the factors which drive the evolution of protease inhibitor
      resistant human immunodeficiency virus type-1 in the absence of drugs. To examine
      if viral replicative capacity (RC) is an important determinant, we performed in
      vitro evolution experiments in the absence of drugs with a unique panel of 6 drug
      resistant human immunodeficiency virus type-1 recombinant protease variants with
      a range of different RC. The experiments revealed that an increase in viral RC
      was indeed an important determinant of evolution. Initial protease inhibitor
      resistant viruses with only a few protease mutations and a lowered RC evolved
      into viruses with an increased RC, either by reversion of primary resistance
      mutations or by the acquisition of compensatory mutations. For these viruses with
      a lowered RC, higher fitness peaks are most likely available in the sequence
      space. Evolution of these viruses in the absence of drugs will therefore drive
      them to new fitness peaks. In contrast, viruses with an RC comparable to wild
      type or even higher than wild type did not show any evolution. In the case of
      these viruses, it is not so likely that higher fitness peaks are present within
      the sequence space, and therefore, these variants will persist in the absence of
      drug pressure.

PMID- 16645547
TI  - Nonnegligible increasing temporal trends in unprotected anal intercourse among
      men who have sexual relations with other men in montreal.
AB  - OBJECTIVE: To determine temporal trends in unprotected anal intercourse (UAI)
      among men who have sex with men (MSM) participating in the Omega Cohort Study,
      1997 through 2003. METHODS: The Omega Cohort Study was a longitudinal study of
      HIV-negative MSM aged 16 years or older and living in Montreal. Participants
      completed self-administered questionnaires and interviews every 6 months. Trend
      analysis using the generalized estimating equation was done for length of cohort
      membership (visits) and by calendar time for all visits per type of sexual
      partner. Odds ratios (ORs) were calculated to measure the odds of increasing UAI
      per 6-month period. RESULTS: Among subjects who were followed for at least 4
      years, UAI increased with regular seroconcordant partners (OR = 1.06, 95%
      confidence interval [CI]: 1.04 to 1.09) and any type of partner (OR = 1.05, 95%
      CI: 1.03 to 1.07). There was a nonnegligible increase in UAI with casual partners
      (OR = 1.05, 95% CI: 1.01 to 1.09). For the analysis by calendar time, there were
      increases in UAI between regular seroconcordant partners (OR = 1.04, 95% CI: 1.02
      to 1.05) and any type of partner (OR = 1.03, 95% CI: 1.02 to 1.04). There were
      nonnegligible increases in UAI with casual partners (OR = 1.03, 95% CI: 1.00 to
      1.05) and with any type of partner except a regular seroconcordant partner from
      15.7% to 18.8% (OR = 1.02, 95% CI: 1.00 to 1.04). CONCLUSIONS: There was a
      nonnegligible and consistent increase in UAI among Omega Cohort Study
      participants between 1997 and 2003. Continuous trend analysis is important
      because it allows us to follow UAI closely and to implement intervention
      strategies that may help to stop or reduce the present trend.

PMID- 16645548
TI  - Combining PMTCT with active case finding for tuberculosis.
AB  - Tuberculosis (TB) is the preeminent manifestation of HIV infection and has become
      a leading cause of maternal mortality and morbidity in high HIV-prevalence
      settings. Active TB in pregnant women has potentially serious consequences for
      fetuses and newborns. In Soweto, South Africa, there is a more than 90% uptake of
      voluntary counseling and HIV testing during routine antenatal care, and almost
      one third of pregnant women are HIV-infected. The posttest counseling session of
      the prevention of mother-to-child transmission program provides an opportunity to
      screen HIV-infected pregnant women for TB. In this study, 370 HIV-infected
      pregnant women were screened for symptoms of active TB by lay counselors at the
      posttest counseling session. If symptomatic, they were referred to nurses who
      investigated them further. Eight women were found to have previously undiagnosed,
      smear-negative, culture-confirmed TB (2160/100,000). The mean CD4 count in those
      with active TB compared to those without TB was 276 x 10(6) cells per liter vs
      447 x 10(6) cells per liter (P = 0.051). Symptoms most associated with active TB
      were hemoptysis and fever. We conclude that rates of TB in HIV-infected pregnant
      women are high, and screening for TB during routine antenatal care should be
      implemented in high HIV-prevalence settings.

PMID- 16645549
TI  - Model projections on the required coverage of syringe distribution to prevent HIV
      epidemics among injecting drug users.
AB  - BACKGROUND: Although syringe distribution is effective in preventing HIV
      transmission among injecting drug users (IDUs), there is little evidence on the
      required coverage to substantially reduce HIV transmission. METHODS: A
      mathematical model is developed to explore the relationship between the endemic
      HIV prevalence among IDUs and the coverage of syringe distribution. Data from IDU
      populations in the United Kingdom and Belarus are used to explore the
      implications of increasing coverage and the effect of changes in other behaviors.
      RESULTS: Projections suggest that there is a coverage threshold, which, if
      reached, could lead to substantial decreases in HIV prevalence. The threshold
      largely depends on the frequency that IDUs inject and (safely) reuse their
      syringes, and corresponds to less than 4 syringe-sharing events per IDU per
      month. Other factors, such as the injecting cessation rate and efficacy of
      syringe cleaning, only have substantial impact near threshold coverage levels.
      CONCLUSIONS: Our results support a policy of increasing the coverage of syringe
      distribution but highlight the difficulty in producing a universal coverage
      target. Great public health benefit could be conferred by encouraging the safe
      reuse of an IDU's own syringes and small stable injecting groups. Policies that
      discourage this will negate the impact of syringe distribution interventions.

PMID- 16645550
TI  - Rescue therapy with once-daily atazanavir-based regimens for antiretroviral
      experienced HIV-infected patients.

PMID- 16645551
TI  - Does partner selection contribute to sex differences in sexually transmitted
      infection rates among African American adolescents in San Francisco?
AB  - INTRODUCTION: Little is known regarding whether partner characteristics explain
      sex differences in sexually transmitted infection (STI) rates in nonclinic-based,
      school-aged African American youth. MATERIALS AND METHODS: A random digit dial
      household sample of 14- to 19-year-old youth in San Francisco reported the total
      number, age, race, and perceived history of incarceration, gang membership, and
      level of sexual activity of their partners. Youth were tested for gonorrhea and
      chlamydia. RESULTS: Female participants were more likely than male participants
      to have a partner who was older or had been incarcerated and less likely to have
      a non-African American partner. Controlling for partner number, female's odds
      ratio (OR) for having an STI was 1.39 (95% confidence interval [CI] = 0.98-1.98;
      P = 0.07). Controlling for partner incarceration and number of partners, the
      borderline sex difference was eliminated (OR = 1.07; 95% CI = 0.70-1.63).
      CONCLUSION: Sex differences in STI rates among African American adolescents may
      be determined more by the risk of the partner than the risk of the individual.

PMID- 16645552
TI  - Periodic presumptive treatment for cervical infections in service women in 3
      border provinces of Laos.
AB  - OBJECTIVES: The objectives of this study were to determine whether periodic
      presumptive treatment (PPT) for sexually transmitted infections (STIs) in service
      women could be implemented in 3 border provinces of Laos and whether its
      implementation was associated with a reduction in the prevalence of cervical
      infections. STUDY DESIGN: Four hundred forty-two service women were interviewed
      using a standardized questionnaire in 3 border provinces at baseline (day 1) and
      419 3 months (day 90) later. Azithromycin at a dosage of 1 g was administered at
      monthly intervals over 3 months in Khammouane province, on days 1, 30, and 90 in
      Oudomxai and days 1, 60, and 90 in Savannakhet. Urine samples were collected at
      baseline and day 90 for gonorrhea and chlamydia testing. RESULTS: Baseline
      samples showed very high levels of both gonorrhea and/or chlamydia of 42.7% in
      Oudomxai, 39.9% in Khammouane, and 22.7% in Savannakhet. At day 90, after 2 or 3
      rounds of PPT, these were, respectively, 12.3%, 21.9%, and 17.0%. Overall, the
      prevalence of any cervical infection decreased by 45% from 32.4% (95% confidence
      interval [CI] = 28.1-36.9) at day 1 to 18.0% (95% CI = 14.5-22.1) at day 90 (P <
      0.001). CONCLUSIONS: Lower prevalences of cervical infections were observed after
      2 to 3 rounds of PPT. The optimal time between rounds of PPT is uncertain, but
      while these high STI rates prevail, a 1- to 2-month gap is recommended. After the
      introduction of this PPT project, costs of STI drugs reduced 5-fold making PPT a
      sustainable intervention in Laos for service women until user-friendly services
      are developed.

PMID- 16645553
TI  - Gonorrhea prevention and clinical care in the private sector: lessons learned and
      priorities for quality improvement.
AB  - We reviewed literature on gonorrhea prevention and clinical care in the private
      sector, the setting where most gonorrhea cases in the United States are now
      diagnosed. Although most private-sector health settings had a low prevalence of
      gonorrhea (0.1-2.5%), some private emergency departments and specialty clinics
      that serve a large number of high-risk or infected patients had prevalences
      ranged from 1.7% to 11.0%. Studies of diverse settings and populations suggest
      that, in general, diagnostic testing of symptomatic patients (69-83%),
      appropriate treatment (61-100%), and case reporting (64-94%) are delivered more
      commonly than risk assessment for asymptomatic patients (15-28%), routine
      screening of pregnant women (31-77%), risk-reduction counseling (35-78%), and sex
      partner management (0-82%). To sustain the recent declines in gonorrhea incidence
      in the United States, private-sector providers and health systems must continue
      to offer gonorrhea prevention and clinical services and consider implementing
      interventions to improve delivery of risk assessment, risk-reduction counseling,
      and partner management services.

PMID- 16645554
TI  - [Treatment of genital prolapse with a polypropylene mesh inserted via the vaginal
      route. Anatomic and functional outcome in women aged less than 50 years].
AB  - OBJECTIVES: We evaluated the results of surgical insertion of a polypropylene
      mesh via the vaginal route in young women presenting genital prolapse. MATERIAL
      AND METHODS: Retrospective study concerning 20 women under age 50 who underwent
      between July 2000 and December 2003 surgical insertion of an anterior (n=14),
      posterior (n=3) or double (anterior and posterior) (n=3) polypropylene mesh via
      the vaginal route. A minimum follow-up of 6 months was required for inclusion in
      the study. Anatomical results were assessed using the Pelvic Organ Prolapse
      Quantification (POP-Q) according to ICS (International Continence Society)
      recommendations. To document the functional results, the patients answered 3
      validated self-assessment questionnaires related to pelvic symptoms, sexual
      behaviors and quality of life. RESULTS: Mean follow-up was 21 months (6 to 52
      months). A vaginal erosion of the mesh occurred in 2 women (10%). Cystocele
      recurred in one woman among the 17 patients who had an anterior polypropylene
      mesh (Gynemesh, Gynecare, Ethicon). Seventeen women were sexually active before
      the surgical procedure and 19 post-operatively. Among these women, 5 (26%)
      reported alteration of sexual activity after surgery (with dyspareunia in 4 cases
      (21%)), and 14 women (74%) reported no changes or improvement in sexual activity.
      CONCLUSION: Surgical management of genital prolapse using a polypropylene mesh
      inserted via the vaginal route has proven its anatomical efficacy in young women.
      The potential adverse consequences on sexual life would require clinical research
      concerning the surgical approach (abdominal or vaginal route) and synthetic
      materials used in prolapse surgery for young women.

PMID- 16645555
TI  - [Uterine cervical lesions during pregnancy: diagnosis and management].
AB  - OBJECTIVES: To define a practical attitude for the management of pregnant women
      with cervical intraepithelial neoplasia (CIN) and cervical cancer. MATERIALS AND
      METHODS: Review of the literature indexed in Medline. RESULTS: The prevalence of
      the HPV infections is unchanged among pregnant women with infection by low risk
      viruses. The viral load increases at the time of the pregnancy, and decreases in
      the post-partum period. Cervical cytology is easily to perform with reliable
      results: among the 5% of pathological cervical smears, low grade lesions
      predominate. The high grade smears require colposcopic exploration, usefully
      completed by directed biopsies to rule out invasive lesions. Surveillance of high
      grade CIN is required during pregnancy with post-partum control; most regress. In
      France during the year 2000, 189 cancers of the uterine cervix were detected
      during 774.782 pregnancies. Clinical diagnosis is delayed by the non specific
      clinical signs and the histological aspects of the lesions which are identical
      with those observed in young woman. The intrinsic outcome of cancer is not
      modified by pregnancy, and the cesarean section is often preferred (vaginal
      delivery likely facilitates vascular dissemination). For fetal reasons, a
      therapeutic delay can be proposed for small sized lesions with a favourable
      histological subtype and no progression after 20 weeks of gestation. CONCLUSION:
      Pregnancy offers the opportunity to perform cervical smears in women not
      regularly followed. A conservative attitude with a revaluation in postpartum can
      be proposed in the event of diagnosis of CIN during pregnancy. Pregnancy has
      little influence on invasive cervical cancers. Management decisions must be made
      on a case-by-case basis.

PMID- 16645556
TI  - [Progress in ambulatory anesthesia applied to gynecological surgery].
AB  - Ambulatory gynecological surgery enables fast recovery of vital functions,
      ambulation and a relational life of quality. Patients whose disease is well
      controlled at the anesthesia consultation can benefit from ambulatory procedures.
      Improved material and surgical practices broaden potential indications, limiting
      the risk of postoperative pain which can be controlled with simple analgesic
      protocols. The choice of the anesthesic techniques or the agents used during the
      intervention ensures fast recovery of higher functions. Nausea and vomiting,
      which may develop after returning home and compromise oral drug intake, must be
      prevented. More ambulatory gynecological procedures can be expected in the near
      future, pointing out the importance of developing more adapted medical
      structures.

PMID- 16645557
TI  - [What about fellowship for French residents in obstetrics and gynecology?].
AB  - OBJECTIVES: Evaluation of French fellowship positions in Obstetrics and
      Gynecology (OG). MATERIALS AND METHODS: We sent a questionnaire to the
      representative of the French OG training association (Association des
      Gynecologues-Obstetriciens en Formation, AGOF) of the 26 regions of France. We
      counted the fellowship positions in university and non university teaching
      hospitals. We also enumerated the French residents in OG. This gave an estimate
      of how many French residents in OG will accede to a fellowship position in
      university and non university teaching hospitals. RESULTS: We counted 876 French
      residents in OG and 257 fellowship positions: 154 in university hospitals and 103
      in non university hospitals. We estimated that 43.9% of French residents in OG
      will accede to a fellowship position in university hospitals and 73.2% in non
      university hospitals. CONCLUSION: 73.3% of French residents in OG will accede to
      a fellowship position, with 43.9% in a university hospital.

PMID- 16645558
TI  - [Accidental exposure to blood by midwives in French maternity units: results of
      the national surveillance 2003].
AB  - OBJECTIVE: Midwives appear to be the health care workers exposed to the highest
      rates of bloodborne injury. In this paper - based on a national survey - we
      describe the bloodborne injuries occurring in this profession. MATERIAL AND
      METHOD: During the year 2003, 241 hospitals took part in a national survey of
      bloodborne injuries. Employees registered anonymous standardized reports of
      bloodborne events with the Occupational Medicine Unit. The data were processed by
      the coordination center for the fight against nosocomial infections (C. CLIN)
      which is in charge of the national analysis of all the events reported in this
      database. RESULTS: 169 of the 6973 bloodborne events reported during 2003 (2.4%),
      were signed by midwives or midwife students. The first three most frequent
      accidents reported were: ocular projections during childbirth, pricks when
      repairing episiotomy, pricks or cuts when handling soiled instruments.
      CONCLUSION: Improving knowledge of risk as well as promotion of
      protection/prevention measures well adapted to this profession should be helpful
      in optimizing future attitudes.

PMID- 16645559
TI  - [Changes in the methods of practitioners of fetal medicine after the Perruche
      judgement and the law passed on the 4th of March 2002].
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of the "Perruche
      case" and that of law issued on the 4th of March 2002 in order to moderate the
      effect of the case on the daily practice of prenatal diagnosis and fetal
      medicine. MATERIALS AND METHODS: We sent questionnaires to the 186 sonologists of
      two French regions. Changes in their daily practice, as well as communication
      with the parents to-be, teaching, and stake in a discussion about the future of
      their specialty were evaluated. RESULTS: We received 54 answers (29%). Diagnosis
      and prognosis of fetal anomalies have become more difficult to expose than before
      for 40% of them. Written information as well as medical reports or explanation
      about ability and limits of ultrasound have been improved, in content for 64% and
      in use for 42%. For 45% of practitioners, it has become particularly important to
      carefully chose words used with patients. Some clinicians stopped or limited
      second (60%) and third (45%) trimester scans. They expressed their need to learn
      about legal regulations (50%) or improve communication skills (44%). About 60%
      felt the Perruche case and the subsequent law help to improve reflection about
      the future of fetal medicine and prenatal scans. CONCLUSION: While the law was
      poorly perceived by many physicians, it has enabled a careful reorganization and
      formalization of fetal medicine and particularly prenatal scans. Further debate
      is needed on the objectives of fetal sonography. Practitioners themselves should
      initiate this discussion.

PMID- 16645560
TI  - [Delivery of a macrosomic infant: factors predictive of failed labor].
AB  - OBJECTIVE: To determine risk factors of failed labor in case of fetal macrosomia.
      MATERIALS AND METHODS: Medical charts of two hundred and forty six women who
      delivered macrosomic infants (>4,000g) between January 2004 and May 2005 were
      reviewed. Maternal and obstetrical data were analyzed by mode of delivery.
      Univariate and multivariate (logistic regression analysis) were performed to
      identify risk factors of failed labor. RESULTS: Rate of cesarean delivery was
      18.3%. Indications for cesarean were: failure to progress in 55.6%, arrest in
      fetal descent in 22.2%, fetal distress in 6.7%, and other in 8.9%. There was a
      higher risk of failed labor in nulliparous women (p<0.001), in case of a
      symphysio-fundal measurements>34cm (p=0.004), in nulliparity associated with
      symphysio-fundal measurements>34cm (p<0.001), in case of previous cesarean
      delivery (p=0.004), in cases of maternal height<1.65m (p=0.02), and with ocytocin
      use (p=0.05). In multivariate analysis, nulliparity associated with symphysio
      fundal measurements>34cm (OR=5.2; CI 1.5-18.4), previous cesarean section
      (OR=3.7; CI 1.1-12.4) and maternal height<1.65m (OR=2.6; CI 1.2-5.5) were
      independent factors of failed labor. CONCLUSION: Failure of labor in case of
      macrosomia can be predicted in the event of previous cesarean section, shorter
      maternal height, and association of nulliparity and symphysio-fundal
      measurements>34cm.

PMID- 16645561
TI  - [Mirror pre-eclampsia: Ballantyne's syndrome. Two cases].
AB  - We report two cases of Ballantyne's syndrome which was first described in
      association with foeto-placental hydrops caused by rhesus isoimmunization. Our
      two cases occurred in association with materno-fetal parvovirus infection.
      Although the pathogenic mechanism remains to be fully elucidated, fluid retention
      and hyperplacentation are the main features. Together with these two case
      reports, a literature review confirmed the diverse nonimmunological etiologies
      associated with Ballantyne's syndrome. Clinicians should be aware of this
      particular presentation of hydrops fetalis resulting from a mechanism different
      from hypotrophic placentation because specific etiological treatment can avoid
      unnecessary pregnancy termination. Pre-conception counselling is also different.

PMID- 16645562
TI  - [Dissection of renal artery aneurysm in a pregnant woman with Elhers-Danlos
      disease type IV].
AB  - Recall the clinical signs and personal and family medical history suggestive of
      Elhers-Danlos syndrome, mainly type IV. Review of literature and presentation of
      a clinical case observed in a female patient with Elhers-Danlos disease type IV
      who developed dissection of a renal artery during pregnancy. The prevalence of
      the syndrome is increasing, reaching, according to the latest publications
      1/5,000 births. It is important to determine the type of syndrome to assess
      prognosis. In the classic type and in the hyper mobile type, pregnancy is
      generally well tolerated although certain complications linked to connective
      tissue dysfunction such as pelvic instability, premature delivery, bleeding
      postpartum and perineal lacerations, may develop. Ehlers-Danlos syndrome can be
      associated with serious and even fatal complications for these patients: vascular
      dissection or uterine rupture. It is important for obstetricians to be aware of
      the clinical signs and symptoms suggestive of Elhers-Danlos syndrome in a
      pregnant patient and to know the diagnostic possibilities and potential risks. If
      a typeIV syndrome is diagnosed, it is very important to inform the patient about
      the potential implications for pregnancy and maternal health, as well as the risk
      of transmission to the child and the possibility of antenatal diagnosis.

PMID- 16645563
TI  - [Pelvic Burkitt lymphoma mimicking an ovarian tumor].
AB  - Primary malignant lymphoma of the ovary is a rare tumor (1,5% of ovarian tumors).
      Clinically, it occurs as an abdominal mass with pain which can be confused with
      an epithelial ovary tumor. Most tumors are observed during the fourth decade.
      Burkitt lymphoma, is sporadic in western countries, usually with abdominal
      involvement. Diagnosis is guided by biological analysis and imaging. Prognosis
      depends on medullary and neuromeningeal involvement. Polychemotherapy is
      required. We report a case of a young woman who developed abdominal Burkitt
      Lymphoma mimicking advanced-stage bilateral ovarian cancer.

PMID- 16645564
TI  - [Acute per-partum feto-fetal transfusion. A case study on two sets of twins].
AB  - Description of acute per-partum feto-fetal transfusion. The risk of twin-twin
      transfusion syndrome in monochorionic twin pregnancies is well known. This
      pathology starts in the second trimester and has a chronic course. Acute per
      partum feto-fetal transfusion seems to be less frequent and has not been studied.
      In the study, we described two cases of acute per-partum feto-fetal transfusion.
      The outcomes of the pregnancies were as follows: following a successful delivery,
      the first set of twins presented hypovolemic shock at birth due to an acute
      anemia. The second set of twins was polyglobulic, but otherwise healthy at birth.
      The risk of hypovolemic shock seems to be unpredictable, even if the pregnancy is
      monitored. Obstetricians and pediatricians must keep this pathology in mind when
      dealing with this kind of pregnancy. Moreover, it would be interesting to obtain
      systematically a full blood count of each set of twins of monochorionic
      pregnancies, in order to detect every case of feto-oetal transfusion.

PMID- 16645565
TI  - [Intravesical migration of intrauterine device resulting in stone formation].
AB  - The migration into the bladder of an intrauterine contraceptive device (IUCD) by
      uterine perforation is a rare complication. We report two cases of IUCD which
      migrated into the bladder and subsequently became calcified. The two patients
      having had their IUCD respectively for 3 and 13 years. Revealing signs were
      related to bladder irritation for the first patient and hematuria for the second.
      The diagnosis was suggested on the plain abdominal X-ray and on ultrasound and
      was confirmed by cystoscopy. Ballistic lithotripsy of the bladder stone with
      endoscopic extraction of the IUCD was then performed. Performing a transvaginal
      sonographic examination of the pelvic organs, especially of the uterine anatomy
      is interesting before insertion of an intrauterine contraceptive device (IUCD),
      and repeat transvaginal sonographic examinations immediately after the insertion
      and 4-12 weeks later are advisable. This approach would permit early detection of
      any complications related to insertion of the IUCD.

PMID- 16645567
TI  - [The surgical mask and type A streptococcus in the maternity ward].

PMID- 16645568
TI  - [About the article: "Use of antithrombotic agents in pregnant women" (J Gynecol
      Obstet Biol Reprod, no 8-2005)].

PMID- 16645569
TI  - Nonfatal occupational injuries and illnesses among workers treated in hospital
      emergency departments--United States, 2003.
AB  - CDC's National Institute for Occupational Safety and Health (NIOSH) collects data
      on nonfatal occupational injuries and illnesses through the National Electronic
      Injury Surveillance System (NEISS), an emergency department (ED)-based
      surveillance system. This report summarizes data for 2003. The overall number and
      rate of occupational injuries and illnesses did not change substantially during
      the 5-year period since data were last reported in 1998. In 2003, age-, sex-, and
      diagnosis-related patterns of injury and illness among workers treated in EDs (ED
      treated injuries/illnesses) were similar to those reported in 1998. To achieve
      substantial decreases in these injuries and illnesses, prevention efforts must
      focus on effective, targeted workplace-safety interventions for diverse
      occupations.

PMID- 16645570
TI  - Fatalities among volunteer and career firefighters--United States, 1994-2004.
AB  - Approximately 800,000 firefighters in the United States are volunteer
      firefighters and 300,000 are career firefighters. Volunteer firefighters
      primarily serve communities with fewer than 25,000 inhabitants, whereas most
      career firefighters serve communities of more than 25,000 persons. To
      characterize fatalities among volunteer and career firefighters, CDC analyzed
      data from the U.S. Fire Administration (USFA). This report summarizes the results
      of that analysis and, to illustrate the most common types of volunteer and career
      firefighter fatalities, describes two cases investigated by the National
      Institute for Occupational Safety and Health (NIOSH) Firefighter Fatality
      Investigation and Prevention Program. Fifty-three percent (610 of 1,141) of U.S.
      firefighters who died while on duty during 1994-2004 were volunteers, and 32%
      (368) were career firefighters. The remaining 15% (163) of deaths were among
      other firefighters (e.g., wildland, paid on-call, and part-time paid
      firefighters). Among volunteer firefighters, sudden cardiac death (e.g., from
      myocardial infarction or arrhythmia) and motor vehicle (MV) crashes during
      emergency response were the leading causes of fatality. Among career
      firefighters, sudden cardiac death and asphyxiation were leading causes of death.
      Adoption and enforcement of existing fire-service recommendations regarding
      fitness standards, mandatory medical evaluations with appropriate work
      restrictions, and emergency vehicle response protocols are needed to prevent
      these fatalities among firefighters.

PMID- 16645571
TI  - Health hazard evaluation of police officers and firefighters after Hurricane
      Katrina--New Orleans, Louisiana, October 17-28 and November 30-December 5, 2005.
AB  - In the weeks after Hurricane Katrina struck the U.S. Gulf Coast on August 29,
      2005, reports of increased injuries and symptoms of physical illness and
      psychological strain among New Orleans police officers and firefighters prompted
      CDC to conduct a health hazard evaluation of these two groups. Questionnaires
      were distributed to members of the New Orleans Police Department (NOPD) and New
      Orleans Fire Department (NOFD) 7-13 weeks after the hurricane. This report
      summarizes the results of that evaluation, which determined that upper
      respiratory and skin rash symptoms were the most common physical symptoms
      reported by police officers and firefighters and lacerations and sprains were the
      most common injuries. In addition, approximately one third of the respondents
      reported either depressive symptoms or symptoms of posttraumatic stress disorder
      (PTSD), or both. These results underscore the need to incorporate the safety and
      health of emergency responders into existing disaster preparedness plans and to
      provide periodic responder training and education in tasks unique to disaster
      situations. Clinical follow-up of the physical and psychological health of
      emergency responders should be conducted to better understand, monitor, and treat
      their health conditions.

PMID- 16645572
TI  - Progress toward interruption of wild poliovirus transmission--worldwide, January
      2005-March 2006.
AB  - Progress toward global poliomyelitis eradication was made in 2005, despite the
      diversion of major financial and human resources to control outbreaks resulting
      from wild poliovirus (WPV) importations primarily from Nigeria. The number of
      countries with endemic polio has decreased to four, compared with 125 in 1988,
      when the Polio Eradication Initiative was initiated by the World Health Assembly
      . In Africa and Asia, only eight of the 22 previously polio-free countries that
      were reinfected since 2003 reported WPV transmission after July 2005, and
      transmission was curtailed substantially in all eight of these countries except
      Somalia. Of the three remaining polio-endemic countries in Asia (Afghanistan,
      India, and Pakistan), India and Pakistan also moved closer to eradication in
      2005, reporting approximately half as many cases in 2005, compared with 2004.

PMID- 16645574
TI  - Investigation of avian influenza (H5N1) outbreak in humans--Thailand, 2004.
AB  - INTRODUCTION: Beginning in late 2003, a substantial outbreak of influenza A
      (H5N1) virus spread among poultry in Thailand. On January 23, 2004, the Ministry
      of Public Health (MPH) detected the first confirmed human case of H5N1 infection
      in humans. METHODS: During February-November 2004, the MPH's Bureau of
      Epidemiology and provincial health offices worked together to investigate the
      H5N1 outbreak in humans. Two studies were conducted: a descriptive study to
      describe clinical manifestations and epidemiologic characteristic of the cases
      and a matched case-control study to determine risk factors for persons who might
      subsequently become ill with H5N1. RESULTS: A total of 16 patients with confirmed
      H5N1 were identified for the case-control study. Fever and respiratory symptoms
      predominated. Leucopenia and thrombocytopenia were present respectively in nine
      (100%) and four (44%) persons aged <15 years. Direct touching of unexpectedly
      dead poultry was the most significant risk factor (odds ratio = 29.0; 95%
      confidence interval = 2.7-308.2). Overall mortality was 75%; mortality for
      persons aged <15 years was 90%, compared with 57% for persons aged > or =15
      years. CONCLUSION: Avian influenza was more severe in children, who should avoid
      handling dead poultry during epizootics. Early avian influenza in children
      resembled the more common dengue fever, but presence of cough and absence of
      hemoconcentration distinguished avian influenza, which often progressed rapidly
      to acute respiratory distress syndrome, requiring intensive care.

PMID- 16645575
TI  - Occupational injuries among workers in the cleansing section of the City
      Council's Health Services Department--Bulawayo, Zimbabwe, 2001-2002.
AB  - INTRODUCTION: During 2001-2002, a total of 97 occupational injuries occurred
      among workers in the cleansing section of the Bulawayo, Zimbabwe, City Council's
      Health Services Department. This report describes a study that was conducted to
      describe the nature of these injuries and determine the associated risk factors.
      METHODS: A retrospective, descriptive cross-sectional survey was conducted
      concerning occupational injuries incurred by workers in the cleansing section
      during 2001-2002. A total of 153 workers who had been in the section as of
      January 1, 2001, and 23 senior managers and section supervisors were interviewed,
      the occupational injury register was reviewed, and a walk-through survey was
      conducted to estimate risk factors. RESULTS: The occupational injury register
      indicated that during the study period, 62 workers sustained 67 injuries,
      including one that was fatal. Of these 67 injuries, 27 (40%) involved workers who
      sustained cuts inside a box-type refuse removal truck, and 11 (16%) involved
      workers who had sprained ankles and wrists as a result of improper lifting.
      Workers aged 18-25 years were more likely to incur an injury than workers aged
      >25 years. Working as a bin loader and not having received preemployment training
      were associated with injuries. None of the bin loaders had received preemployment
      training. Hazards identified during the walk-through survey included use of small
      jacks in workshops, contact with biologic and chemical materials on trucks and
      landfill sites, and poor use of protective clothing. Supervisors cited worker
      negligence as the main cause of injury, whereas 72 (84%) workers cited lack of
      adequate protective clothing as a source of injury, and eleven (7%) workers cited
      use of inappropriate equipment. CONCLUSION: On the basis of the modifiable risk
      factors for injury identified in this study, the Bulawayo City Council drafted a
      new health and safety training manual. New recruits now receive training before
      starting work on refuse collection trucks.

PMID- 16645576
TI  - Progress toward tuberculosis control and determinants of treatment outcomes-
      Kazakhstan, 2000-2002.
AB  - INTRODUCTION: In Kazakhstan, during 1995-2002, the annual notification rate per
      100,000 population for new cases of tuberculosis (TB) increased from 67.1 to
      165.1. Beginning in 1998, public health authorities have used the national case
      management strategy (DOTS) promulgated by the World Health Organization (WHO) to
      control TB. Intended goals of DOTS include achieving a cure rate of >85% for
      persons with newly detected pulmonary TB sputum-smear-positive (PTB+) cases and
      having PTB+ represent >65% of all PTB cases among adults. Surveillance data
      collected during 2000-2002 were analyzed to evaluate progress toward achieving
      these goals and identify factors associated with specific treatment outcomes.
      METHODS: Surveillance data included the following nonidentifiable information on
      persons with newly reported cases of PTB: dates of disease onset and treatment
      initiation; methods of diagnosis; treatment outcomes; HIV status; and selected
      demographic, socioeconomic, and behavioral characteristics. Cure rates and
      proportions of PTB+ cases were calculated on the basis of the TB case definition
      and treatment outcome classification format outlined in DOTS guidelines issued by
      WHO. Denominator data to calculate rates were obtained from the National Census
      Office of Kazakhstan. Logistic regression was employed to investigate factors
      associated with treatment outcomes using Epi Info version 3.2. RESULTS: During
      2000-2002, a total of 65,011 new cases of PTB were detected in Kazakhstan. The
      average annual countrywide notification rate per 100,000 population was 146.0;
      provincial notification rates varied (range: 65.1-274.0). The countrywide cure
      rate for newly detected PTB+ was 72.2%; provincial rates varied (range: 65%-81%).
      Of 59,905 cases of PTB among adults during 2000-2002, a total of 26,804 (44.7%)
      were PTB+. Unfavorable treatment outcome of new PTB+ cases was associated with
      alcohol abuse, homelessness, and previous incarceration. CONCLUSION: The cure
      rate for new PTB+ cases and the proportion of cases of PTB+ among all adults with
      PTB were below targeted goals. This might, in part, be explained by the 1998
      adoption of DOTS. Improving program indicators requires evaluation of detection
      efforts, laboratory diagnostic capabilities, and adherence to treatment regimens,
      especially in provinces in which rates are high and among persons at high risk
      for unfavorable treatment outcomes.

PMID- 16645577
TI  - Estimation of measles vaccination coverage using the Lot Quality Assurance
      Sampling (LQAS) method--Tamilnadu, India, 2002-2003.
AB  - INTRODUCTION: As part of the global strategic plan to reduce the number of
      measles deaths in India, the state of Tamilnadu aims at > or =95% measles
      vaccination coverage. A study was conducted to measure overall coverage levels
      for the Poondi Primary Health Center (PPHC), a rural health-care facility in
      Tiruvallur District, and to determine whether any of the PPHC's six health
      subcenters had coverage levels <95%. METHODS: The Lot Quality Assurance Sampling
      (LQAS) method was used to identify health subcenters in the PPHC area with
      measles vaccination coverage levels <95% among children aged 12-23 months.
      Lemeshow and Taber sampling plans were used to determine that the measles
      vaccination status of 73 children aged 12--23 months had to be assessed in each
      health subcenter coverage area, with a 5% level of significance and a decision
      value of two. If more than two children were unvaccinated, the null hypothesis
      (i.e., that coverage in the health subcenter was low [<95%]) was not rejected. If
      the number of unvaccinated children was two or fewer, the null hypothesis was
      rejected, and coverage in the subcenter was considered to be good (i.e., > or
      =95%). All data were pooled in a stratified sample to estimate overall total
      coverage in the PPHC area. RESULTS: For two (33.3%) of the six health subcenters,
      more than two children were unvaccinated (i.e., coverage was <95%). Combining
      results from all six health subcenters generated a coverage estimate of 97.7%
      (95% confidence interval = 95.7-98.8) on the basis of 428 (97.7%) of 438 children
      identified as vaccinated. CONCLUSION: LQAS techniques proved useful in
      identifying small health areas with lower vaccination coverage, which helps to
      target interventions. Monthly review of vaccination coverage by subcenter and
      village is recommended to identify pockets of unvaccinated children and to
      maintain uniform high coverage in the PPHC area.

PMID- 16645578
TI  - Bacterial meningitis among cochlear implant recipients--Canada, 2002.
AB  - INTRODUCTION: In July 2002, a cluster of bacterial meningitis (BM) cases was
      identified among European cochlear implant recipients (CIRs), prompting Health
      Canada to conduct a retrospective cohort study to determine the rate of BM
      infection among Canadian CIRs and to identify risk factors for acquiring BM.
      METHODS: A survey was mailed to 1,432 Canadian CIRs who had received implants
      during January 1995-July 2002 to assess occurrence of postimplant BM infection.
      Data collection included demographics, episodes of meningitis, and vaccination
      status. RESULTS: A total of 1,024 (72%) surveys were completed. Median age of
      CIRs at implantation was 16 years (range: 7 months-81 years). Five (0.5%) cases
      of BM infection were reported (two pneumococcal, one meningococcal, and two of
      unknown etiology); one CIR died. Four cases occurred among children aged <18
      years. Time between implantation and BM infection varied (range: 7 months-7.7
      years; median: 11 months). The rate of BM infection per 1,000 person-years was
      0.7 among CIRs aged > or =18 years and 2.9 among those aged <18 years. The
      proportion of CIRs vaccinated against pneumococcal and meningococcal disease was
      low (46% and 41%, respectively). Preimplant meningitis was identified as a risk
      factor for postimplant BM (p = 0.002). No other risk factors evaluated were
      associated with an increased risk for BM infection. CONCLUSION: CIRs have a high
      rate of postimplant BM infection. Preimplant BM infection was identified as a
      risk factor. Cases of BM infection might have been prevented through vaccination.

PMID- 16645579
TI  - Risk factors for neonatal tetanus--Busoga region, Uganda, 2002-2003.
AB  - BACKGROUND: Uganda has not achieved the 2005 neonatal tetanus (NNT) global
      elimination target set by the World Health Organization (WHO). The Busoga region
      has the highest recorded level of NNT incidence in Uganda. To understand the
      reasons for this high incidence, a study was conducted to identify NNT risk
      factors. METHODS: During March-May 2004, a matched case-control study was
      conducted in the Busoga region for a 2-year study period (2002-2003). Matching
      variables were sex, residence, and date of birth. A total of 24 cases of NNT
      (according to the WHO case definition) were identified from hospital records, and
      96 community controls (children who survived the neonatal period) were selected.
      RESULTS: Bivariate analysis indicated that neonates with NNT were more likely to
      have been delivered outside a health facility, on an unclean surface, without use
      of gloves, or by unskilled attendants. Mothers of these neonates were less likely
      to report vaccination during previous pregnancies, administration of 2 doses of
      tetanus toxoid (TT) during the study pregnancy, or use of certain intravaginal
      substances (most commonly, herbs) at onset of labor. Multivariate analysis
      indicated that unclean delivery surfaces (odds ratio [OR] = 38.8; 95% confidence
      interval [CI] = 2.9-518.1) and primigravidae mothers (OR = 79.5; CI = 1.8
      3,472.2) were associated with NNT. Administration of 2 doses of TT during
      pregnancy, vaccination during previous pregnancies, and intravaginal application
      of certain substances were protective against NNT. CONCLUSION: These findings
      underscore the importance of having clean delivery surfaces and of mothers
      receiving 2 doses of TT during pregnancy. Implementation of these measures might
      help eliminate NNT from the Busoga region of Uganda.

PMID- 16645580
TI  - Risk factors for brucellosis--Leylek and Kadamjay districts, Batken Oblast,
      Kyrgyzstan, January-November, 2003.
AB  - INTRODUCTION: Brucellosis is a zoonotic disease that is associated with chronic
      serious sequelae in humans. During 1997-2002, the reported incidence of human
      brucellosis in Kyrgyzstan increased nearly twofold, from 20 to 36 per 100,000
      population. In 2002, the highest incidence of brucellosis was reported in two
      rural districts of Batkan Oblast: Leylek (106 per 100,000 population) and
      Kadamjay (80 per 100,000 population). During January-November 2003, trainees from
      the Applied Epidemiology Training program in Central Asia conducted a matched,
      hospital-based, case-control study to identify risk factors for brucellosis and
      describe the epidemiology of disease in these two districts. METHODS: Brucellosis
      cases were defined on the basis of epidemiologic, clinical, and laboratory
      criteria. During January-November 2003, a total of 100 persons with confirmed
      brucellosis were identified in the infectious disease wards of the two district
      hospitals; these persons were matched by age and date of admission to 100
      controls who were admitted to other hospital wards for unrelated conditions. Data
      on socioeconomic and occupational factors and history of exposure to animals and
      animal products were collected by using a structured questionnaire. Conditional
      logistic regression was used to study the association between exposure variables
      and brucellosis. RESULTS: Among the 100 persons with confirmed brucellosis during
      the study period, 86 (86%) owned farm animals, and 45 (45%) became ill during
      April-May, the birthing season for farm animals. Multivariate analysis indicated
      that brucellosis was associated with exposure to aborted farm animals in the
      household (odds ratio [OR] = 29.8; 95% confidence interval [CI] = 4.4-203.4) and
      consumption of home-made milk products obtained from bazaars or neighbors (OR =
      11.4; CI = 1.6-83.9). Knowledge of the mode of brucellosis transmission appeared
      to be protective against disease transmission (OR = 0.2; CI = 0.03-0.8).
      DISCUSSION: Exposure to aborted home-owned animals and consumption of home-made
      milk products obtained from bazaars or neighbors were identified as probable
      sources of human brucellosis infections in the study districts. This finding
      suggests that brucellosis spreads among farm animals in the area and that home
      made milk products are not adequately pasteurized. CONCLUSION: To reduce the
      burden of brucellosis in Batken Oblast, veterinary services should be improved,
      and health education programs should be increased. Implementing these measures
      should minimize exposure to farm animals and reduce the risk for infection from
      locally produced milk products.

PMID- 16645581
TI  - Salmonellosis outbreak among factory workers--Huizhou, Guangdong Province, China,
      July 2004.
AB  - INTRODUCTION: During July 9--14, 2004, an outbreak of gastroenteritis occurred
      among workers at an electronics factory in Huizhou, Guangdong Province, China;
      199 cases were reported. A case-control investigation was initiated to identify
      the agent and the mode of transmission. METHODS: Stool samples were collected
      from 142 workers and food handlers and cultured for enteric pathogens. A
      questionnaire concerning meals and foods eaten in the factory cafeteria during
      July 11--13 was administered to 92 ill workers and 100 controls. RESULTS: Of
      approximately 2,000 workers who worked during the outbreak, 197 (10%) had illness
      consistent with the case definition. Salmonella enteritidis was identified from
      44 (31%) of 142 stool samples collected from ill workers. Ill workers were more
      likely than controls to have eaten breakfast in the factory cafeteria during July
      11--13. Of eight foods served at breakfast in the factory cafeteria, three were
      associated with illness: cake, bread (on July 12 only), and congee (i.e., rice
      porridge). Stratification of bread and congee exposure by cake consumption
      indicated that only bread eaten on July 12 was associated with gastroenteritis.
      The cake was baked on July 11, and a mixture that included raw eggs was poured on
      top; the cake was then stored at room temperature and served for breakfast on 3
      consecutive days (July 11--13). The bread was stored together with the cake on
      July 11 and 12. No leftover food was tested. DISCUSSION: The investigation
      indicated that an outbreak of S. enterica serotype Enteritidis resulted from
      consumption of an unusual food vehicle (i.e., cake) that had been contaminated
      from a more typical source (i.e., raw eggs). The bread was stored at room
      temperature together with cake on which a mixture made from raw eggs had been
      poured. The bread was probably contaminated by contact with the cake. CONCLUSION:
      Food handlers should be instructed that intact fresh eggs can harbor S.
      enteritidis, foods made from eggs must be cooked, and prepared food must be
      stored under refrigeration.

PMID- 16645582
TI  - Varicella outbreak among primary school students--Beijing, China, 2004.
AB  - INTRODUCTION: On June 9, 2004, a varicella outbreak was reported in a Beijing
      primary school affecting approximately 80% of children in one preschool
      classroom. An outbreak investigation was initiated to identify factors
      contributing to the high rate of transmission and to assess the effectiveness of
      control measures. METHODS: A varicella case was defined as onset of a
      generalized, vesicular pruritic rash lasting >4 days in a student at the school
      during January 1-June 26, 2004. Parents of all students in the four lowest grades
      (K-2) were questioned concerning varicella illness before January 1, 2004.
      Exposure and vaccination histories of 111 ill students and 120 control students
      with no history of varicella were compared. RESULTS: During January 1-June 26,
      2004, of 1,407 students, 138 (9.8%) had varicella; 488 (35%) K-2 students had no
      history of varicella before the outbreak. In five classrooms in which attack
      rates (ARs) were high (>40%), a primary-case student had remained in school 2
      days while ill with a rash. The secondary attack rate (SAR) in these classrooms
      was 21%, compared with 1.7% in classrooms in which the first ill student was sent
      home immediately (risk ratio [RR] = 10; 95% confidence interval [CI] = 3.7-29.0).
      A total of 111 (70%) ill students rode the school bus daily, compared with 120
      (33%) control students (odds ratio [OR] =4.9; CI = 2.7-9.0). A total of 73 (33%)
      ill students had a history of varicella vaccination before January 1, 2004,
      compared with 32 (69%) control-students (OR = 0.22; CI = 0.08-0.59). CONCLUSION:
      Students who were not excluded from school on the first day of rash were key
      contributors to the spread of varicella in their classrooms. High susceptibility
      to varicella at school entry indicates that vaccination of susceptible students
      might be the only effective measure to control this recurrent problem.

PMID- 16645583
TI  - Polyarginine-mediated protein delivery to dendritic cells presents antigen more
      efficiently onto MHC class I and class II and elicits superior antitumor
      immunity.
AB  - Protein transduction domains (PTDs) have been used increasingly to deliver
      reagents to a variety of cell types in vitro and in vivo. We have previously
      shown that HIV TAT-PTD-containing whole protein antigens (Ags)-transduced
      dendritic cells (DCs) stimulated Ag-specific CD8+ and CD4+ T cells. Although the
      cytotoxic T lymphocytes (CTL) activity generated was sufficient to prevent
      engraftment of mice with Ag-expressing tumors, treatment of tumor-bearing mice
      with TAT-PTD Ag-transduced DCs resulted in tumor regression in some animals.
      Recently, several other PTDs were reported to promote higher transduction
      efficiencies than TAT-PTD. To evaluate the role of individual PTDs in induction
      of immune responses in tumor vaccination studies, we engineered recombinant
      fusion Ovalbumin (OVA) that contained three differrent PTDs, including the most
      efficacious known PTD (polyarginine (R9)-PTD). Our results demonstrated that R9
      PTD-containing OVA transduced DCs most efficiently, and that transduction
      efficacy was closely correlated with the extent of Ag-specific CD4+ and CD8+ T
      cell activation in vitro and in vivo. Repeated vaccination with R9-PTD-OVA
      transduced DC in (OVA-expressing) tumor-bearing mice induced enhanced antitumor
      immunity, and elicited complete rejection of tumors when DC was co-injected with
      adjuvants. This vaccination strategy may be clinically applicable, and offers
      theoretical and practical advantages to those that are in current use.

PMID- 16645584
TI  - Number of nevi at a specific anatomical site and its relation to cutaneous
      malignant melanoma.
AB  - The risk of cutaneous malignant melanoma (CMM) is strongly associated with total
      number of nevi. Scanty information is available on the association between CMM at
      a specific anatomical site and number of nevi at the same site. We analyzed data
      from a case-control study conducted in Italy between 1992 and 1994, on 542 cases
      of CMM and 538 hospital controls. Cases and controls were examined by trained
      dermatologists who counted the number of melanocytic nevi. We derived
      multivariate odds ratios (ORs) and 95% confidence intervals (95% CIs) of site
      specific risk of CMM for high versus low number of nevi at the corresponding
      site. The ORs of CMM for the highest versus the lowest tertile of number of nevi
      at the corresponding site was 1.4 (95% CIs: 0.7-2.8) at face and neck, 2.3 (95%
      CIs: 1.1-4.9) at anterior trunk, 4.9 (95% CIs: 2.9-8.4) at posterior trunk, 2.9
      (95% CIs: 1.2-6.6) at upper limbs and 5.0 (95% CIs: 2.9-8.5) at lower limbs. In a
      case-case analysis, comparing CMM cases at a specific site and CMM cases at all
      other sites, the only excess risk was found for the posterior trunk, the ORs
      being 2.1 (95% CIs: 1.2-3.6) for the highest versus the lowest tertile of number
      of nevi. Our data do not support the hypothesis of a specific effect of nevi at
      each single anatomical site.

PMID- 16645585
TI  - Comparison of wound closure after burn and cold injury in human skin equivalents.

PMID- 16645586
TI  - Severe acne vulgaris and tobacco smoking in young men.
AB  - As the relationship between tobacco smoking and acne remains unclear, we examined
      the relationship between cigarette smoking and severe acne in a large cohort of
      young men. Trained nurses interviewed subjects upon discharge from compulsory
      military service, regarding family history, habits, and tobacco smoking habits.
      Data was correlated with severe acne status, as diagnosed and coded by board
      certified dermatologists. In total, 27,083 male subjects participated in the
      study from 1983 to 2003, of which 237 (0.88%) had severe acne, 11,718 (43.27%)
      were active smokers, and 15,365 (56.73%) were nonsmokers at the time of
      interviews. Active smokers showed a significantly lower prevalence of severe acne
      (0.71%) than nonsmokers (1.01%) (P = 0.0078). An inverse dose-dependent
      relationship between severe acne prevalence and daily cigarette consumption
      became significant from 21 cigarettes a day (chi2 and trend test: P < 0.0001),
      odds ratio: 0.2 (95% CI: 0.06-0.63). The study did not aim to establish a
      temporal correlation, and passive smoking and acne treatments were not measured.
      Previous in vitro and clinical studies strongly support an association with
      nicotine. We suggest a trial with topical nicotine treatment for acne to further
      investigate this association.

PMID- 16645587
TI  - Epidermal morphogenesis: the transcriptional program of human keratinocytes
      during stratification.
AB  - The epidermis serves to protect the body against environmental assaults and at
      the same time is able to survive and replenish itself under harsh conditions. The
      epidermis accomplishes this feat via a well-orchestrated program of
      stratification and terminal differentiation that provides barrier against
      infection, radiation, and water loss. Despite significant progress in skin
      biology, many molecules and pathways that are involved in stratification and
      barrier formation remain unknown. Here, we employed tissue-engineered models of
      complete versus impaired epidermal stratification to discover the genes that may
      be important in this process. Transcriptional profiling at different stages of
      development showed significant differences in transcription, signaling, and most
      important metabolism-associated genes between fully stratified and poorly
      stratified epithelia. These transcriptional changes correlated well with
      functional data on cell proliferation, expression of adhesion molecules, and
      utilization of metabolic pathways, ultimately leading to different phenotypes.
      Our data identified genes that were not previously known to play a role in
      epidermis and established a link between metabolism and morphogenesis in skin
      epithelium.

PMID- 16645588
TI  - Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor
      suppressive functions in highly metastatic melanoma cells.
AB  - The loss of cell cycle control in malignant melanomas is thought to be due to a
      lack of retinoblastoma protein (pRb) activity. We have recently reported a
      progressive deficiency of the retinoblastoma-binding protein 2-homolog 1 (RBP2
      H1) in advanced and metastatic melanomas in vivo, suggesting a role of RBP2-H1 in
      loss of pRb-mediated control. Therefore, in this study, we re-established the pRb
      modulating function of RBP2-H1 in highly metastatic A375-SM melanoma cells by re
      expressing its C-term (cRBP2-H1). As previously shown, the corresponding domains
      comprise the pRb-binding region of the RBP2-H1 protein (non-T/E1A-pRb-binding
      domain (NTE1A)). As a result, we detected pRb-hypophosphorylation selectively at
      Ser795, but not at Ser780 and Ser807/811 throughout the G1 phase of the cell
      cycle. As a further consequence, a block in G1/S transition was observed
      accompanied by a significant decrease of DNA replication and cellular
      proliferation. As demonstrated by cDNA microarrays of cRBP2-H1-transduced cells
      and confirmed by quantitative TaqMan reverse transcriptase-PCR, differential
      expression of melanoma-progression-related genes was observed, among them bone
      morphogenetic protein 2, follistatin, transforming growth factor alpha,
      hepatocyte growth factor, transcription factor 4 and microphthalmia-associated
      transcription factor. Conclusively, these data suggest that RBP2-H1 exerts a
      broad tumor-suppressive function partially mediated by pRb modulation. Therefore,
      re-establishing of RBP2-H1 could evolve as an interesting novel approach in
      developing experimental treatments for metastatic melanomas.

PMID- 16645589
TI  - Innovative liposomes as a transfollicular drug delivery system: penetration into
      porcine hair follicles.
AB  - Liposomes had been widely used for drug delivery in the past. In this study, five
      different liposomes were used as a follicular delivery system in pig ear skin.
      The liposomes mainly differed in their sphere diameter, lipid composition, and
      surface charge. A novel class of liposomes being amphoteric in their charge
      behavior are compared to established anionic and cationic liposomes. Two
      different fluorescent dyes, hydrophilic carboxyfluoresceine or lipophilic
      curcumin, were enclosed in the liposomes and used as model drugs. The fluorescent
      dyes were also applied in a standard formulation for reference. The penetration
      depth of the dyes was measured by laser scanning microscopy in histological
      sections. One hour, 3, 5, and 7 days after application, biopsies were taken and
      the penetration depth into the hair follicle was measured in longitudinal
      sections. The liposomes showed a higher penetration depth compared to the
      standard formulation. The relative penetration depth of the dyes, applied in the
      standard formulation, averaged 30% of the full follicle length during the whole
      observation period, whereas the liposomal formulations penetrated considerably
      deeper into the hair follicles. Amphoteric and cationic liposomes reached an
      average relative penetration depth of approximately 70% of the full hair follicle
      length.

PMID- 16645590
TI  - The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in
      cutaneous T-cell lymphoma cell lines through the AKT pathway.
AB  - Enzastaurin displays pro-apoptotic properties against a spectrum of malignancies
      and is currently being investigated in clinical trials. We have investigated the
      effects of enzastaurin on the viability of the cutaneous T-cell lymphoma cell
      lines HuT-78 and HH by using 3-(4,5-dimethylthiazol-2-yl)-5(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, cell cycle
      analysis, propidium iodide and annexin-V staining, and caspase-3-mediated
      proteolytic activation. Enzastaurin-treatment decreased cell viability, increased
      annexin V-FITC-positive cells, and increased the proportion of sub-G1 populations
      in both cell lines that was not reversed by the T-cell growth stimulating
      cytokines IL-2, IL-7, IL-15. Enzastaurin-induced cell death involved caspase-3
      activated cleavage of poly(ADP-ribose) polymerase that was inhibited by the pan
      caspase inhibitor ZVAD-fmk, whereas the increase in sub-G1 population was only
      partially inhibited by ZVAD-fmk. Furthermore, enzastaurin downregulated AKT
      activity and its downstream effectors GSK3beta and ribosomal protein S6. The
      phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the
      growth and survival of hematologic malignancies and inhibition of this pathway is
      considered as a therapeutic target. Protein kinase C activation contributes to
      PI3K/AKT activation, but it is unknown how enzastaurin may interfere with
      signaling through this pathway. These results demonstrate that enzastaurin, at
      clinically achievable concentrations, induces apoptosis and affects AKT
      signaling, and provide a rationale for further in vivo studies addressing the
      therapeutic efficacy in cutaneous T-cell lymphoma patients.

PMID- 16645591
TI  - Hair cycle control by vanilloid receptor-1 (TRPV1): evidence from TRPV1 knockout
      mice.

PMID- 16645592
TI  - Identification of gene expression changes induced by chemical allergens in
      dendritic cells: opportunities for skin sensitization testing.
AB  - Cellular changes within resident skin dendritic cells (DCs) after allergen uptake
      and processing are critical events in the acquisition of skin sensitization. Here
      we describe the development of a set of selection criteria to derive a list of
      potential target genes from previous microarray analyses of human peripheral
      blood-derived (peripheral blood mononuclear cells (PBMCs)-DCs) treated with
      dinitrobenzene sulfonic acid for predicting skin-sensitizing chemicals. Based on
      those criteria, a probing evaluation of the target genes has been conducted using
      an extended chemical data set, comprising five skin irritants and 11 contact
      allergens. PBMCs-DCs were treated for 24 hours with various concentrations of
      chemicals and in each instance the expression of up to 60 genes was examined by
      real-time PCR analysis. Consistent allergen-induced changes in the expression of
      many genes were observed and further prioritization of the targets was conducted
      by analysis of the same genes in DCs treated with non-sensitizing chemicals to
      determine their specificity for skin sensitization. Real-time PCR analyses of
      multiple chemical allergens, irritants, and non-sensitizers have identified 10
      genes that demonstrate reproducibly high levels of selectivity, specificity, and
      dynamic range consistent with providing the basis for robust and sensitive
      alternative approaches for the identification of skin-sensitizing chemicals.

PMID- 16645593
TI  - Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis:
      Gene regulation and cellular effects.
AB  - We assessed expression of IL-20 and its receptors in psoriasis, given the recent
      implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin
      consistently expressed more IL-20 mRNA than nonlesional (NL) skin.
      Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized
      to infiltrating CD68+/CD11c+ (myeloid-derived) dermal leukocytes. Because this
      contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA
      expression in a variety of cells in vitro, and confirmed a myeloid-derived
      cellular source (monocytes). Plastic adhesion, activation of beta2 integrins, and
      incubation with tumor necrosis factor-alpha stimulated expression in these cells.
      IL-20 receptor (IL-20R)alpha and IL-20Rbeta mRNA was decreased in LS versus NL
      skin, which also contrasted with earlier findings. To investigate the
      relationship between IL-20 and disease activity, we examined psoriasis patients
      treated with the CD2-targeted agent alefacept. In therapeutic responders,
      lesional IL-20 mRNA decreased to NL levels, suggesting that CD2+ leukocytes may
      proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays
      to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease
      related and IFN-gamma-induced genes. Hence, IL-20 may influence inflammation
      through IFN-like effects. Together, these data indicate that IL-20 may be an
      important effector cytokine in psoriasis, and that its inhibition may represent a
      potential therapeutic target.

PMID- 16645594
TI  - Distinct roles for IL-1 receptor type I signaling in early versus established
      Leishmania major infections.
AB  - IL-1alpha/beta released by infected dendritic cells (DC) plays a critical role in
      the development of protective immunity against Leishmania major. Previous studies
      demonstrated that treatment of susceptible BALB/c mice with IL-1alpha during T
      cell priming (days 1-3 post-infection) induced T helper (Th)1-mediated
      protection. In contrast, we now demonstrate that prolonged treatment with IL
      1alpha (for 3 weeks) worsened disease outcome. To characterize the receptor
      involved, L. major infections in IL-1 receptor type I (IL-1RI) knockout mice were
      studied. In C57BL/6 IL-1RI-/- mice, the IL-1alpha-mediated protective effect was
      abrogated. The course of high-dose infection (2 x 10(5) parasites) in IL-1RI-/-
      mice was not different from controls. Surprisingly, in low-dose infections (10(3)
      parasites), IL-1RI-/- mice developed approximately 50% smaller lesions compared
      to wild types, decreased parasite loads and increased IFNgamma/IL-4 ratios.
      Interestingly, naive Th0 and Th2, but not Th1, cells expressed IL-1RI ex vivo. We
      conclude that IL-1RI mediates the effect of IL-1alpha in leishmaniasis in C57BL/6
      mice. In addition, IL-1 appears to play distinct roles in Th education and
      maintenance. In early phases of physiologically relevant, low-dose L. major
      infections, IL-1 facilitates Th1 development from Th0 cells, whereas later on IL
      1RI signaling promotes Th2 expansion and worsens disease outcome. Effects of IL-1
      on disease outcome may be related to levels of IL-1RI on Th subpopulations.

PMID- 16645596
TI  - Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in
      the mouse skin model adopted for epidermal powdered immunization.
AB  - Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles
      ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely
      that the relative volumetric distribution of LCs and keratinocytes within the
      epidermis impacts on the efficacy of Gene Gun immunization protocols. This study
      quantified the three-dimensional (3D) distribution of LCs and keratinocytes in
      the mouse skin model with a near-infrared multiphoton laser-scanning microscope
      (NIR-MPLSM). Stratum corneum (SC) and viable epidermal thickness measured with
      MPLSM was found in close agreement with conventional histology. LCs were located
      in the vertical plane at a mean depth of 14.9 microm, less than 3 mum above the
      dermo-epidermal boundary and with a normal histogram distribution. This likely
      corresponds to the fact that LCs reside in the suprabasal layer (stratum
      germinativum). The nuclear volume of keratinocytes was found to be approximately
      1.4 times larger than that of resident LCs (88.6 microm3). Importantly, the ratio
      of LCs to keratinocytes in mouse ear skin (1:15) is more than three times higher
      than that reported for human breast skin (1:53). Accordingly, cross-presentation
      may be more significant in clinical Gene Gun applications than in pre-clinical
      mouse studies. These interspecies differences should be considered in pre
      clinical trials using mouse models.

PMID- 16645595
TI  - Defining the regulatory elements in the proximal promoter of DeltaNp63 in
      keratinocytes: Potential roles for Sp1/Sp3, NF-Y, and p63.
AB  - p63, a homolog of the tumor suppressor p53, plays an important role in the
      formation of stratified epithelium such as those in the epidermis of the skin.
      The p63 gene gives rise to multiple functionally distinct protein isoforms,
      including the DeltaNp63 class of isoforms, which lacks the N-terminal
      transactivation domain and is synthesized from an internal promoter. DeltaNp63
      proteins are the predominant isoforms expressed in keratinocytes and are thought
      to be important for maintenance of the proliferative capacity of these cells.
      Here, we have examined the transcriptional control mechanisms that govern the
      expression DeltaNp63 in keratinocytes. We first performed DNase I hypersensitive
      site mapping and demonstrated that the promoter region of DeltaNp63 is in open
      chromatin state in keratinocytes. To identify the cis-elements that regulate
      DeltaNp63, we have performed transient transfection assays in keratinocytes with
      several DeltaNp63 promoter constructs. This identified a short evolutionarily
      conserved fragment that harbors most of the transcriptional activity of the
      DeltaNp63 promoter. Biochemical studies of this element have revealed critical
      roles for CCAAT-box-binding factor (CBF/NF-Y) and Sp1/Sp3 family of proteins. In
      addition, our data suggest that DeltaNp63 is recruited to and can activate its
      own promoter, possibly through protein-protein interactions, thus providing an
      auto-regulatory loop of self-regulation. These studies support the notion that
      unique and distinct pathways control the expression of individual p53 family
      members and their various isoforms.

PMID- 16645597
TI  - The epidemiology of nevi and signs of skin aging in the adult general population:
      Results of the KORA-survey 2000.
AB  - Nevi can approximate the melanoma risk and demographic changes will increase the
      meaning of signs of skin aging (SSA). However, little is known about the
      epidemiology of nevi and SSA in the general adult population. We aimed to
      estimate the prevalence and age distribution of common and atypical nevi and SSA
      as well as gender differences in a large population-based sample. Within the
      Cooperative Health Research in the Augsburg Region (KORA) in Germany, a
      population-based survey was performed. Data were gathered by interview and the
      number of pigmented lesions and presence of SSA were obtained by dermatological
      examination. A total of 2,823 adults (mean age 49 years, 50% women) participated
      (response 67%). Most subjects (60.3%) exhibited 11 to 50 common nevi and 5.2% had
      at least one atypical nevus. 51.9% were diagnosed with elastosis (Cutis
      rhomboidalis nuchae, 18.3%; Morbus Favre Racouchot 1.4%). Ephelides were seen in
      16%, lentigines solaris in 62.4%, and lentigines seniles in 33.2%. All signs of
      skin aging increased significantly with age and so did lentigines solaris,
      seniles, and actinic keratoses. In contrast, common and atypical nevi and
      ephelides decreased significantly with age. Signs of skin aging are frequent and
      increase, in contrast to common and atypical nevi, with age.

PMID- 16645598
TI  - MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas.
AB  - In this study, we assessed the role of melanocortin 1 receptor (MC1R) variants
      and of two patched (PTCH) polymorphisms (c.3944C>T (P1315L), insertion 18 bp IVS1
      83) as risk factors for basal cell carcinoma (BCC) in the French population. The
      population investigated comprised 126 BCC patients who were enrolled on the basis
      of specific criteria (multiple and/or familial BCC and/or onset before the age of
      40 years and/or association with another tumor)--and 151 controls matched for
      ethnicity, age, and sex. MC1R variants appeared as a moderate risk factor for BCC
      (odds ratio (OR) for one and two variants, 2.17 [1.28-3.68] and 7.72 [3.42
      17.38], respectively), independently of pigmentation characteristics (OR = 2.53
      [1.34-4.8]). Interestingly, in addition to the predictable red hair color (RHC)
      alleles, two non-RHC alleles (V60L and V92M) were also closely associated with
      BCC risk (OR 3.21 [1.91-5.38] and 2.87 [1.5-5.48], respectively), which differs
      from the situation in the Celtic population. In addition, the PTCH c.3944C/C
      genotype was also associated with BCC risk (OR 1.94 [1.2-3.1]), especially in the
      subgroup of patients with multiple tumors (OR 2.16 [1.3-3.6]). Thus, our data
      show that MC1R and PTCH variants are associated with BCC risk in the French
      population. We further suggest that assessing MC1R and PTCH status could be
      useful, combined with the assessment of clinical risk factors, in identifying
      high-risk patients to be targeted for prevention or more rigorous surveillance.

PMID- 16645604
TI  - Too invasive for routine use.

PMID- 16645606
TI  - OLAW issues guidance on the use of telecommunications for IACUC meetings.

PMID- 16645607
TI  - Punctual professor using passe procedures. Answer unclear.

PMID- 16645608
TI  - Punctual professor using passe procedures.

PMID- 16645609
TI  - Punctual professor using passe procedures. Cut the funds.

PMID- 16645610
TI  - Punctual professor using passe procedures. Contrary to the 3 Rs.

PMID- 16645611
TI  - Marked swelling with coalescing ecchymoses of the lower mandible in a Xenopus
      laevis frog.

PMID- 16645613
TI  - Pain and distress: what really matters?
AB  - Federal regulations mandate the minimization of both pain and distress in
      laboratory animals. That no clear definition exists for 'distress' complicates
      its recognition, quantification, and alleviation. The author argues that IACUCs
      and investigators should shift their focus from pain to distress, and that in
      doing so both problems will be better dealt with. She discusses criteria for
      defining 'significant' distress, and offers suggestions for the conduct of
      studies to determine levels of distress.

PMID- 16645614
TI  - Fishing for genes influencing vertebrate behavior: zebrafish making headway.
AB  - The zebrafish (Danio rerio) has been a favorite model of developmental biologists
      and geneticists, but only recently have investigators begun to appreciate its
      usefulness in behavior genetics. Papers focusing on the behavior or brain
      function of this species were once extremely rare, but during the past decade
      rapid growth has taken place. Despite the increased interest, however, the number
      of studies devoted to the analysis of the behavior of this species is still
      orders of magnitude less than those conducted on more traditional laboratory
      subjects including the rat and the mouse. The authors review selected literature
      and demonstrate that zebrafish is an excellent subject for behavior genetics
      research, especially in the area of forward genetics (mutagenesis).

PMID- 16645615
TI  - Bone marrow aspiration from rats: a minimally invasive procedure.

PMID- 16645616
TI  - AALAS certification exam study guidance.

PMID- 16645617
TI  - Genome-wide analysis of mammalian promoter architecture and evolution.
AB  - Mammalian promoters can be separated into two classes, conserved TATA box
      enriched promoters, which initiate at a well-defined site, and more plastic,
      broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to
      several hundred thousand transcription start sites (TSSs) in the mouse and human
      genomes, allowing precise analysis of the sequence architecture and evolution of
      distinct promoter classes. Different tissues and families of genes differentially
      use distinct types of promoters. Our tagging methods allow quantitative analysis
      of promoter usage in different tissues and show that differentially regulated
      alternative TSSs are a common feature in protein-coding genes and commonly
      generate alternative N termini. Among the TSSs, we identified new start sites
      associated with the majority of exons and with 3' UTRs. These data permit genome
      scale identification of tissue-specific promoters and analysis of the cis-acting
      elements associated with them.

PMID- 16645618
TI  - IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen
      derived peptides or recombinant protein effectively stimulate specific Type-1
      CD4+ T-cell responses from normal donors and melanoma patients in vitro.
AB  - Although CD4(+) Type-1T helper (Th1) cells secreting interferon-gamma (IFN-gamma)
      appear to play an essential role in promoting durable antitumor immunity, we have
      previously shown that patients with cancer exhibit dysfunctional Th1-type
      responses against epitopes derived from tumor antigens, such as MAGE-A6. Here, we
      engineered human dendritic cells (DCs) to secrete high levels of the IFN-gamma
      inducing cytokines, interleukin (IL)-12p70 and IL-18, via recombinant adenoviral
      infection to generate an in vitro stimulus capable of promoting previously
      deficient patient Th1-type responses. Dendritic cells co-infected with Ad.IL-12
      and Ad.IL-18 (DC.IL-12/18) were more effective at stimulating MAGE-A6-specific
      Th1-type CD4(+) T-cell responses than DCs infected with either of the cytokine
      vectors alone, control Ad.Psi5 virus or uninfected DCs. Furthermore, we show that
      DC.IL-12/18 loaded with recombinant MAGE-A6 protein (rMAGE) and used as in vitro
      stimulators promote Th1-type immunity that is frequently directed against
      multiple MAGE-A6-derived epitopes. The superiority of DC.IL-12/18-based
      stimulations in melanoma patients was independent of disease stage or current
      disease status. Based on these results, we believe this modality may prove
      clinically useful as a vaccine platform to promote the recovery of tumor antigen
      specific, Th1-type CD4(+) T-cell responses in patients with cancer.

PMID- 16645619
TI  - A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor
      prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated
      modification of CD34+ peripheral blood cells with O6-methylguanine DNA
      methyltransferase.
AB  - Administration of chemotherapy is often limited by myelosuppression. Expression
      of drug-resistance genes in hematopoietic cells has been proposed as a means to
      decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a
      retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to
      transduce hematopoietic progenitors, which were subsequently used in the setting
      of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis
      brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral
      blood progenitor cells were collected by apheresis and enriched for CD34+
      expression. Nine subjects were infused with CD34+-enriched cells treated in a
      transduction procedure involving a 4-day exposure to cytokines with vector
      exposure on days 3 and 4. No major adverse event was related to the gene therapy
      procedure. Importantly, the engraftment kinetics of the treated product was
      similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo
      manipulation did not significantly reduce engrafting progenitor cell function.
      Gene-transduced cells were detected in all subjects. Although the level and
      duration was limited, patients receiving cells transduced using fibronectin
      'preloaded' with virus supernatant appeared to show improved in vivo marking
      frequency. These findings demonstrate the feasibility and safety of utilizing
      MGMT-transduced CD34+ peripheral blood progenitor cells in the setting of
      chemotherapy.

PMID- 16645620
TI  - Enhancement of antitumor activity of herpes simplex virus gamma(1)34.5-deficient
      mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide.
AB  - Current oncolytic viruses exert only limited antitumor activity on their own.
      There is a need to increase their oncolytic capability. We evaluated the effect
      of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor
      activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for
      human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide
      increased the viral yield, especially at a low input multiplicity of infection
      (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene
      bisacetamide treatment promoted the cytopathic effect of R849 and increased the
      proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic
      cells in R849-infected cells as compared with parental HSV-1(F)-infected cells.
      The growth of oral SCC xenografts in nude mice was markedly suppressed by
      treatment with R849 in combination with HMBA, and the survival of the co-treated
      animals was significantly prolonged as compared with that of animals treated with
      R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and
      trigeminal neurons, but not in brain, lung, liver, and kidney. These results
      indicate that HMBA enhances the antitumor activity of R849 through the expression
      of immediate early genes without increasing its toxicity. Hexamethylene
      bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1
      mutants.

PMID- 16645621
TI  - Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen
      generate long-term tumor-specific immunity.
AB  - Alphavirus vectors have emerged as a promising strategy for the development of
      cancer vaccines and gene therapy applications. In this study, we used the
      replication-defective vaccine vector SIN replicon particles from a new packaging
      cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT)
      linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein.
      The linkage of CRT to E7 in SIN replicon particles resulted in a significant
      increase in E7-specific CD8(+) T-cell precursors and a strong antitumor effect
      against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon
      particles enhanced presentation of E7 through the major histocompatibility
      complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and
      pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons.
      Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon
      particles also generated significant reduction of lung tumor nodules, suggesting
      that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7
      replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long
      term in vivo tumor protection effects and antigen-specific memory immunities. We
      concluded that the CRT strategy used in the context of SIN replicon particles
      facilitated the generation of a highly effective vaccine for cancer prophylaxis
      and immunotherapy.

PMID- 16645622
TI  - Evidence of Waite-Beetham lines in the corneas of diabetic patients as detected
      by in vivo confocal microscopy.

PMID- 16645623
TI  - Evidence-based practice in acute ophthalmology.
AB  - AIM: To study the overall level of evidence-based practice in an accident and
      emergency eye unit in the UK and evaluate the extent of evidence-based practice
      by ophthalmologists and nurse practitioners (NPs). METHODS: The case notes of all
      new patients attending our accident and emergency department for a period of 1
      week were reviewed prospectively. For each case, the diagnosis at presentation
      and its intervention was ascertained. A literature search using Medline and
      Cochrane library was performed to assess the level of evidence provided for each
      diagnosis-intervention pair. Each diagnosis-intervention pair was evaluated and
      graded to assess the best level of evidence provided. RESULTS: A total of 474 new
      patients attended the eye casualty during the study period. No diagnosis was made
      in 27 cases and they were excluded from the analysis. Out of 447 patients, 308
      (68.9%) cases were managed by NPs and 139 (31.1%) by doctors. A total of 294
      (65.8%) patient interventions were based on evidence from systematic reviews,
      meta-analysis and randomised-controlled trials, of which 223 were managed by NPs
      and 71 by ophthalmologists. This difference was statistically significant with
      P<0.001. One hundred and seven (23.9%) interventions were supported by evidence
      from prospective and retrospective trials. CONCLUSION: This study demonstrated
      that two-thirds of interventions were based on the highest level of evidence and
      was comparable to studies performed in other specialities. It also highlights the
      advanced role of trained NPs in acute ophthalmology.

PMID- 16645624
TI  - Third nerve paralysis as a presenting sign of essential thrombocythaemia.

PMID- 16645625
TI  - Reversible pupillary dilation following botulinum toxin injection to the lateral
      rectus.

PMID- 16645626
TI  - Horner's syndrome: an atypical presentation in a child with neurofibromatosis
      type 2.

PMID- 16645627
TI  - Unusual ultrasound biomicroscopy appearance after non-penetrating trabecular
      surgery with SK gel implant.

PMID- 16645628
TI  - Corneal thickness and visual field damage in glaucoma patients.
AB  - PURPOSE: To verify whether there was a significant correlation between central
      corneal thickness (CCT) and visual field damage in patients with primary open
      angle glaucoma (POAG). METHODS: A total of 99 eyes with POAG were consecutively
      recruited. Patients were classified as glaucomatous based on visual field and
      optic nerve head damage. All underwent applanation tonometry, Humphrey perimetry,
      and measurement of CCT with ultrasonic pachymetry. Based on CCT value, the sample
      was split at the mode in two groups (group 1<535 microm, n=49; group 2>or=535
      microm, n=50). RESULTS: Entire cohort: mean CCT 554 microm+/-45.03; mean
      deviation (MD) -6.68 dB+/-7.32; pattern standard deviation (PSD) 5.33+/-3.75;
      intraocular pressure (IOP) 17.91+/-4.16 mmHg with treatment. Group 1: CCT was
      504.8 microm+/-30.8; MD -9.01 dB+/-8.72; PSD 6.38+/-3.99; IOP 18.02 mmHg+/-4.66.
      Group 2: mean CCT 574.6 microm+/-35.03; MD -4.39 dB+/-4.70; PSD 4.25+/-3.19; IOP
      17.79 mmHg+/-3.57. A significant difference was found between the two groups for
      both MD and PSD. Linear regression analysis showed a significant correlation
      between CCT and PSD (P<0.001). CONCLUSIONS: Our data show that patients with a
      thinner cornea had a worse MD and PSD. As a thinner CCT causes an underestimation
      of the true IOP, there may be a delay in the diagnosis of POAG or an inadequate
      estimate of the clinical course despite apparently desirable IOP applanation
      readings.

PMID- 16645629
TI  - Dilated examination of patients referred with minor lid complaints--is it
      necessary?
AB  - OBJECTIVE: To evaluate whether dilated fundus examination is necessary on
      patients presenting to clinic with lid complaints and normal vision. METHODS:
      Patients with lid complaints were recruited from general and emergency clinics.
      Patients with visual symptoms or previous ophthalmic history were excluded.
      Subjects were examined by a junior ophthalmologist with slit-lamp biomicroscopy
      and Goldmann tonometry. Dilated posterior segment examination was performed with
      a Volk lens and the peripheral retina was examined with a three-mirror contact
      lens. RESULTS: A total of 100 patients (200 eyes) were recruited, 63 females and
      37 males with an average age of 45 years (SD of 19 years). The majority of lid
      abnormalities were chalazia (66) and papilloma (21). Posterior segment findings
      were early cataracts in five cases (eight eyes), macular drusen in three cases
      (five eyes), peripheral retinal lattice degeneration in two cases (three eyes),
      retinal pigment epithelial changes in one case (two eyes), a choroidal naevus in
      one eye, choroidal atrophy in one eye, and one case with asymmetric disc cupping.
      Six patients were seen by senior ophthalmologists and all were discharged after
      the first visit. CONCLUSIONS: In our sample of 100 patients presenting with lid
      complaints and normal visual acuity, dilated examination revealed no sight
      threatening conditions that required further treatment or regular follow-up.
      Therefore, a single episode of screening for nonspecified retinal disease in a
      group with no particular risk factors is an inefficient screening method.

PMID- 16645630
TI  - Increased and persisted subretinal haemorrhage after photodynamic therapy for
      choroidal neovascularization secondary to angioid streaks.

PMID- 16645631
TI  - Unusual acute angle closure after air descemetopexy.

PMID- 16645632
TI  - p73 cooperates with Ras in the activation of MAP kinase signaling cascade.
AB  - The p73 gene is capable of inducing cell cycle arrest, apoptosis, senescence,
      differentiation and to cooperate with oncogenic Ras in cellular transformation.
      Ras can be considered as a branch point in signal transduction, where diverse
      extracellular stimuli converge. The intensity of the mitogen-activated protein
      kinase (MAPK) cascade activation influences the cellular response to Ras. Despite
      the fundamental role of p53 in Ras-induced growth arrest and senescence, it
      remains unclear how the Ras/MEK/ERK pathway induces growth arrest in the absence
      of p53. We report here that oncogenic Ras stabilizes p73 resulting in p73
      accumulation and enhancement of its activity. p73, in turn, induces a sustained
      activation of the MAP kinase cascade synergizing with oncogenic Ras. We also
      found that inhibition of p73 function modifies the cellular outcome to Ras
      activation inhibiting Ras-dependent differentiation. Here, we show for the first
      time that there is a signaling loop between Ras-dependent MAPK cascade activation
      and p73 function.

PMID- 16645633
TI  - NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to
      delay Wallerian degeneration.
AB  - The slow Wallerian degeneration protein (Wld(S)), a fusion protein incorporating
      full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays
      axon degeneration caused by injury, toxins and genetic mutation. Nmnat1
      overexpression is reported to protect axons in vitro, but its effect in vivo and
      its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice
      whose Nmnat activities closely match that of Wld(S) mice. Nmnat1 overexpression
      in five lines of transgenic mice failed to delay Wallerian degeneration in
      transected sciatic nerves in contrast to Wld(S) mice where nearly all axons were
      protected. Transected neurites in Nmnat1 transgenic dorsal root ganglion explant
      cultures also degenerated rapidly. The delay in vincristine-induced neurite
      degeneration following lentiviral overexpression of Nmnat1 was significantly less
      potent than for Wld(S), and lentiviral overexpressed enzyme-dead Wld(S) still
      displayed residual neurite protection. Thus, Nmnat1 is significantly weaker than
      Wld(S) at protecting axons against traumatic or toxic injury in vitro, and has no
      detectable effect in vivo. The full protective effect of Wld(S) requires more N
      terminal sequences of the protein.

PMID- 16645634
TI  - BH3-only proteins in cell death initiation, malignant disease and anticancer
      therapy.
AB  - Induction of apoptosis in tumour cells, either by direct activation of the death
      receptor pathway using agonistic antibodies or recombinant ligands, or direct
      triggering of the Bcl-2-regulated intrinsic apoptosis pathway by small molecule
      drugs, carries high hopes to overcome the shortcomings of current anticancer
      therapies. The latter therapy concept builds on a more detailed understanding of
      how Bcl-2-like molecules maintain mitochondrial integrity and how BH3-only
      proteins and Bax/Bak-like molecules can undermine it. Means to unleash the
      apoptotic potential of BH3-only proteins in tumour cells, or bypass the need for
      BH3-only proteins by blocking possible interactions of Bcl-2-like prosurvival
      molecules with Bax and/or Bak allowing their direct activation, constitute
      interesting options for the design of novel anticancer therapies.

PMID- 16645635
TI  - Novel synergistic mechanism for sst2 somatostatin and TNFalpha receptors to
      induce apoptosis: crosstalk between NF-kappaB and JNK pathways.
AB  - Somatostatin is a multifunctional hormone that modulates cell proliferation,
      differentiation and apoptosis. Mechanisms for somatostatin-induced apoptosis are
      at present mostly unsolved. Therefore, we investigated whether somatostatin
      receptor subtype 2 (sst2) induces apoptosis in the nontransformed murine
      fibroblastic NIH3T3 cells. Somatostatin receptor subtype 2 expression induced an
      executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src
      homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B
      (NF-kappaB) activity and subsequent inhibition of the mitogen-activated protein
      kinase JNK. Tumor necrosis factor alpha (TNFalpha) stimulated both NF-kappaB and
      c-Jun NH2-terminal kinase (JNK) activities, which had opposite action on cell
      survival. Importantly, sst2 sensitized NIH3T3 cells to TNFalpha-induced apoptosis
      by (1) upregulating TNFalpha receptor protein expression, and sensitizing to
      TNFalpha-induced caspase-8 activation; (2) enhancing TNFalpha-mediated activation
      of NF-kappaB, resulting in JNK inhibition and subsequent executioner caspase
      activation and cell death. We have here unraveled a novel signaling mechanism for
      a G protein-coupled receptor, which directly triggers apoptosis and crosstalks
      with a death receptor to enhance death ligand-induced apoptosis.

PMID- 16645636
TI  - Comparison of chemical inhibitors of antiapoptotic Bcl-2-family proteins.

PMID- 16645637
TI  - Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy.
AB  - Ischemia and reperfusion (I/R) injury is associated with extensive loss of
      cardiac myocytes. Bnip3 is a mitochondrial pro-apoptotic Bcl-2 protein which is
      expressed in the adult myocardium. To investigate if Bnip3 plays a role in I/R
      injury, we generated a TAT-fusion protein encoding the carboxyl terminal
      transmembrane deletion mutant of Bnip3 (TAT-Bnip3DeltaTM) which has been shown to
      act as a dominant negative to block Bnip3-induced cell death. Perfusion with TAT
      Bnip3DeltaTM conferred protection against I/R injury, improved cardiac function,
      and protected mitochondrial integrity. Moreover, Bnip3 induced extensive
      fragmentation of the mitochondrial network and increased autophagy in HL-1
      myocytes. 3D rendering of confocal images revealed fragmented mitochondria inside
      autophagosomes. Enhancement of autophagy by ATG5 protected against Bnip3-mediated
      cell death, whereas inhibition of autophagy by ATG5K130R enhanced cell death.
      These results suggest that Bnip3 contributes to I/R injury which triggers a
      protective stress response with upregulation of autophagy and removal of damaged
      mitochondria.

PMID- 16645638
TI  - Bim, Bad and Bmf: intrinsically unstructured BH3-only proteins that undergo a
      localized conformational change upon binding to prosurvival Bcl-2 targets.
AB  - All BH3-only proteins, key initiators of programmed cell death, interact tightly
      with multiple binding partners and have sequences of low complexity, properties
      that are the hallmark of intrinsically unstructured proteins (IUPs). We show,
      using spectroscopic methods, that the BH3-only proteins Bim, Bad and Bmf are
      unstructured in the absence of binding partners. Detailed sequence analyses are
      consistent with this observation and suggest that most BH3-only proteins are
      unstructured. When Bim binds and inactivates prosurvival proteins, most residues
      remain disordered, only the BH3 element becomes structured, and the short alpha
      helical molecular recognition element can be considered to behave as a 'bead on a
      string'. Coupled folding and binding is typical of many IUPs that have important
      signaling roles, such as BH3-only proteins, as the inherent structural plasticity
      favors interaction with multiple targets. This understanding offers promise for
      the development of BH3 mimetics, as multiple modes of binding are tolerated.

PMID- 16645639
TI  - ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its
      apoptotic activity.
AB  - In mammals and Drosophila, apoptotic caspases are under positive control of the
      CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen,
      we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The
      ark mutants are loss-of-function alleles characterized by reduced developmental
      apoptosis. Using the phenotypic series of these alleles, we identified helical
      domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic
      activity. Interestingly, the WD40 region may also have an unanticipated positive
      requirement for the apoptotic activity of ARK. Considering structural
      information, we discuss the roles of these domains for assembly and activity of
      the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the
      absence of apoptotic signals, and pro-apoptotic in the presence of such signals.
      Furthermore, a defined null allele reveals that ark is required for most, but not
      all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.

PMID- 16645640
TI  - Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB
      expressing and chemoresistant cells.
AB  - The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4
      thiadiazolidine (P(3)-25) is known to possess anti-bacterial, anti-fungal, anti
      tubercular, and local anesthetic activities. We studied the anti-tumorigenic
      activity of P(3)-25 and the role of nuclear transcription factor kappaB (NF
      kappaB) in this process. In constitutive NF-kappaB-expressing cells, treatment
      with P(3)-25 inhibited the expression of NF-kappaB-dependent reporter gene,
      adhesion molecules, and cyclooxygenase. It downregulated phosphorylation of p65
      by inhibiting upstream kinases, such as protein kinase A and casein kinase II,
      but did not alter NF-kappaB DNA-binding activity. Alone, P(3)-25 induced
      apoptosis in NF-kappaB-expressing and doxorubicin-resistant breast cancer cells,
      and in the presence of other chemotherapeutic agents, it potentiated apoptosis.
      Overall, our results suggest that P(3)-25 exerts antitumorigenic activity by
      inhibiting phosphorylation of p65, the transcriptionally active subunit of NF
      kappaB by inhibiting its upstream kinases, and potentiates apoptosis mediated by
      chemotherapeutic agents. These results suggest novel approaches for designing of
      anticancer drugs for combination chemotherapy.

PMID- 16645641
TI  - Intracellular domains of amyloid precursor-like protein 2 interact with CP2
      transcription factor in the nucleus and induce glycogen synthase kinase-3beta
      expression.
AB  - Amyloid precursor protein (APP) is a member of a gene family that includes two
      APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2
      undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in
      the release of an approximately 6 kDa intracellular C-terminal domain (ICD),
      which can translocate into the nucleus. In this study, we demonstrate that the
      APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus
      and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which
      has broad-ranged substrates such as tau- and beta-catenin. The significance of
      this finding is substantiated by the in vivo evidence of the increase in the
      immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK
      3beta in the AD patients' brain. Taken together, these results suggest that APLP2
      ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through
      the interaction with CP2 transcription factor in the nucleus.

PMID- 16645642
TI  - The effector caspases drICE and dcp-1 have partially overlapping functions in the
      apoptotic pathway in Drosophila.
AB  - Caspases are essential components of the apoptotic machinery in both vertebrates
      and invertebrates. Here, we report the isolation of a mutant allele of the
      Drosophila effector caspase drICE as a strong suppressor of hid- (head involution
      defective-) induced apoptosis. This mutant was used to determine the apoptotic
      role of drICE. Our data are consistent with an important function of drICE for
      developmental and irradiation-induced cell death. Epistatic analysis suggests
      that drICE acts genetically downstream of Drosophila inhibitor of apoptosis
      protein 1 (Diap1). However, although cell death is significantly reduced in drICE
      mutants in all assays, it is not completely blocked. A double-mutant analysis
      between drICE and death caspase-1 (dcp-1), another effector caspase, reveals that
      some cells (type I) strictly require drICE for apoptosis, whereas other cells
      (type II) require either drICE or dcp-1. Thus, these data demonstrate a barely
      appreciated complexity in the apoptotic pathway, and are consistent with current
      models about effector caspase regulation in both vertebrates and invertebrates.

PMID- 16645643
TI  - Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced
      apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB.
AB  - There is growing evidence that the insulin-like growth factor-binding protein 3
      (IGFBP-3) can have IGF-independent effects on cell growth. However, despite the
      fact that IGFBP-3 has been reported to be both antiproliferative and
      proapoptotic, the molecular mechanisms underlying the action of IGFBP-3 have not
      been elucidated. We report that although addition of IGFBP-3 (either synthetic or
      secreted protein) had no effect on cell survival, IGFBP-3 (100 ng/ml)
      significantly enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cell
      death in colonic carcinoma-derived cell lines (20-30% depending on cell line),
      whereas it had no effect on the survival of the TRAIL-resistant adenoma-derived
      cells. Both addition of IGFBP-3 protein to cell cultures or enforced expression
      of IGFBP-3 in the HT29 carcinoma cell line inhibited nuclear factor kappa B (NF
      kappaB) activation in response to the induction of apoptosis by TRAIL. We propose
      that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an
      adjuvant in the treatment of colon cancer.

PMID- 16645645
TI  - Chronic aspirin therapy for the prevention of cardiovascular events: a waste of
      time, or worse?

PMID- 16645666
TI  - Surgery insight: Current advances in percutaneous heart valve replacement and
      repair.
AB  - Several advances have been made in interventional cardiology, particularly in the
      field of valvular heart disease. Among the procedures for which technologies are
      available, percutaneous replacement of the pulmonary and aortic valves, and
      percutaneous repair of the mitral valve, via annuloplasty or the Alfieri method,
      are the best known. Along with the excitement generated by these new
      subspecialties, however, there has also been skepticism. In this article we focus
      on the current innovations that have been applied to the procedures in humans,
      and discuss the advantages and disadvantages of the different strategies.

PMID- 16645667
TI  - Technology insight: Cardiac CT angiography.
AB  - Noninvasive coronary angiography has been the holy grail of cardiovascular
      medicine for decades. Cardiac CT angiography obtained with multislice CT
      technology is finally reaching the high standard in spatial resolution that is
      achieved by invasive X-ray coronary angiography. The latest 64-slice CT
      technology is a fast and safe modality for imaging the heart and coronary
      arteries, with scans taking seconds to complete. The temporal resolution of
      cardiac CT is still inferior, however, to that of invasive angiography,
      echocardiography or cardiac MRI. As such, this technique is still highly
      susceptible to motion artifacts created by the beating heart, and blooming
      artifacts due to the presence of calcium in the atherosclerotic plaque and to
      metallic implants. The routine use of agents to lower the heart rate before
      scanning is still required in most patients, and the timing of the contrast
      injection is critical for obtaining high-quality diagnostic cardiac images.
      Furthermore, cardiac CT angiography exposes the patient to substantial amounts of
      ionizing radiation and nephrotoxic contrast agents and, therefore, patients must
      be carefully selected based on a thorough understanding of the current clinical
      indications. In this review, I discuss the current multidetector row CT
      technology, safety issues, imaging protocols, clinical applications, and some of
      the challenges that still lie ahead with this modality.

PMID- 16645668
TI  - Mechanisms of disease: Genetic mechanisms of atrial fibrillation.
AB  - Atrial fibrillation is the most common cardiac arrhythmia, and it increases in
      prevalence with advancing age to about 6% in people older than 65 years. The
      chance of developing atrial fibrillation at age 40 years or older is about 25% in
      men and women. This arrhythmia accounts for about one-third of all strokes, and
      30% of all patients with atrial fibrillation have a family history of the
      disease. In 1997, Brugada et al. identified the first locus for familial atrial
      fibrillation on chromosome 10q22-24 in three different Spanish families. Since
      that time, seven further loci have been mapped and four relevant genes
      identified. All these genes encode potassium-channel subunits. The mechanism of
      action by which all four genes induce atrial fibrillation is via shortening of
      the action potential duration and atrial effective refractory period. The
      consistency of the mechanism of action beckons the development of therapy
      specifically targeted to prevent these molecular events. In addition to monogenic
      diseases, patients with structural heart disease are predisposed to atrial
      fibrillation by inherited DNA polymorphisms. The development of chips with
      hundreds of thousands of single-nucleotide polymorphisms to perform genome-wide
      scans will elucidate over the next few years the single-nucleotide polymorphisms
      that predispose to atrial fibrillation. Within the next decade, most of the genes
      responsible for atrial fibrillation and the single-nucleotide polymorphisms that
      confer predisposition will probably be identified, and therapies will be
      developed on the basis of individuals' genomic profiles. In this review I provide
      an overview of the understanding of the relevant genetic mutations that have been
      identified so far, and briefly discuss what implications this information might
      have for practice.

PMID- 16645669
TI  - Ventricular pseudoaneurysm associated with severe mitral regurgitation.
AB  - BACKGROUND: A 77-year-old man presented with non-ST-segment elevation myocardial
      infarction, congestive heart failure and cardiogenic shock. In the coronary care
      unit, the patient was initially stabilized by diuresis and afterload reduction.
      Six months previously he had experienced an episode of severe dyspnea, orthopnea
      and chest heaviness. INVESTIGATIONS: Echocardiography and coronary angiography.
      DIAGNOSIS: Ventricular pseudoaneurysm associated with mitral regurgitation after
      myocardial infarction. MANAGEMENT: Pseudoaneurysm repair using a bovine
      pericardial patch, coronary artery bypass grafting of the left anterior
      descending and circumflex coronary artery and management of mitral regurgitation
      by ventricular remodeling.

PMID- 16645671
TI  - [Psychotropic medication consumption in the Buenos Aires general population].
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence of
      psychotropic drug consumption among the general population of the city of Buenos
      Aires. METHODS: A survey was conducted among 1,777 respondents in different
      neighborhoods of the city. RESULTS: At the time of the survey 15,5% of the
      general population was using some kind of psychotropic medication, and life-time
      prevalence of use was 29,4%. Utilization was higher in woman and the elderly.
      There were significant consumption differences by level of educational attainment
      but no by social class. More than 12% of the population was using benzodiazepines
      and 3% antidepressants. Almost 25% of the consumers was using the medication
      without medical advice. Twenty five percent of the users recognized themselves as
      very dependent on these medications. CONCLUSIONS: Psychotropic drug use is very
      extended among the general population of the city of Buenos Aires. Measures to
      restrict the irrational use of these medications and to control them adequately
      should be implemented.

PMID- 16645672
TI  - [Morbidity by drug use, in the emergency room of the general hospital].
AB  - The data were collected by an epidemiological sounding on the emergency room in
      nine representative hospitals of the Province of Buenos Aires. 8.4% of the cases
      of emergencies were related to the abuse of psychoactive substances.
      Approximately two of each ten of these cases are expressed like a violence
      situation towards others or itself and specially affects the population of less
      than 20 years. Alcohol drinks are referred in more than half of the answers on
      substances consumed during the six hours previous to the emergency consultation.
      These results indicate the convenience of maintaining a system of fast soundings
      as central element of the epidemiological monitoring network on consumption of
      psychoactive substances.

PMID- 16645673
TI  - [Sodomites, homosexuals, gay: from persecution to demedicalization].
AB  - Since 1895, when Oscar Wilde was put on trial, almost 80 years passed until the
      beginning of the process that led to delete homosexuality from DSM (APA) and
      contributed to its despenalization. Over that period, moral and legal persecution
      and mass killings in concentrations camps gave way to gay pride. Here we analyze
      this process in relation to DSM and we search for answers to the question of why
      homosexuality between consenting adults was far more persecuted than sexual
      behaviors that clearly affects the rights of other persons as paedophilia or
      rape.

PMID- 16645674
TI  - [Sexuality and death].
AB  - It is intented to show two apparently antithetic poles: Sexuality and Death, in
      fact interpenetrate themselves, disguising the fear of death, or the desire to
      die, Eros' world. Different expressions of culture are analyzed, especially the
      one known as The Profane Time, the time for work, which is characterized by the
      submission to interdicts (prohibitions) and, on the other hand, the Time for Joy
      or The Sacred Time, characterized by the transgression of such prohibitions. Its
      relationship with the interdicts'violations in the sexual as well as in the death
      arena is analyzed in order to connect the human being's fear in the presence of
      the unrestraint, the overflow and the abandonment of the time established for
      work that would imply free sexuality. The latter is connected with some
      conclusions that could be considered useful in the field of Sexual Therapies,
      with a certain critical look at the mechanist settlement applied to those
      treatments.

PMID- 16645675
TI  - [The evolution of the operated transsexual people].
AB  - The objective of the present article is the evaluation of the scientific
      literature on the evolution of operated transsexual people and the consequences
      of the hormonal and surgical treatments. It seems crystal clear that both
      treatments produce much more positive effects than expected by the physicians and
      the psychologists in the past. Together with an appropiated follow-up and a
      correct assessment of the psychological vulnerability, these elements make
      acceptable the demand of sex change. Studies on the "psychological risk profile"
      are necessary to evaluate the factors of further adaptability and also to propose
      preventive steps at the beginning of the hormonal and surgical treatment.

PMID- 16645676
TI  - [Assessment of sexual function from a psychopharmacological viewpoint].
AB  - The aim of this paper is to discuss aspects linked to the assessment of sexual
      activity in mental health patients. Traditionally, and to this day, this
      assessment has received insufficient consideration by intervening professionals.
      Emphasis is made on determining the onset of sexual dysfunction with respect to
      the disorder prompting the visit. Schizophrenia is taken as the paradigm of the
      pathology least considered as regards assessment of the sexual activity of those
      suffering from this disorder.

PMID- 16645677
TI  - [Sexuality and dementia: a case study].
AB  - In this paper we will discuss about sexuality in people with dementia, trying to
      show difficulties that arise and that affect the patient, his or her partner, the
      family and the geriatric institute if the patient lives there. Five clinical
      cases are described and deeply analyzed. Many times psychotropic medications are
      central in the treatment plan for people with dementia and some kind of sexual
      difficulty; but this is not enough. We think that it is necessary to combine
      pharmacologic approaches with others from human sciences that fit with our
      patients' difficulties.

PMID- 16645678
TI  - [Sexual behavior in patients with schizophrenia: a review of the literature and
      survey in patients attending a rehabilitation program].
AB  - Sexual functioning of patients with a severe psychotic illness such as
      schizophrenia has received little attention from clinicians. Sexual dysfunctions
      are an important contributing factor to a poor quality of life in this population
      and important factor in non-adherence to pharmacological treatment. A high
      percentage of individuals with schizophrenia reported to have no sexual
      intercourse or showed evidence of sexual dysfunction (28%; to 40%; in females and
      40%; to 60%; in males), which has different etiology, like the illness itself
      (12%; to 15%;), aging (35%; to 41%;), or side effects from the psychiatric
      medication (26%; to 36%;). We alert about this problems and show the preliminary
      results of a survey in an adult chronic population (ranging between 27 to 57
      years of age, with an equal sex distribution, attending in a psychiatric
      rehabilitation program in a half-way house. RESULTS: a 36%; of the patients
      reported to have sexual difficulties, the 50%; of the sample has had sexual
      intercourse with some regularity, only the 32%; of the sample reported to have
      sex in the last month, and less than a 5%; of this population reported to have a
      regular partner, among others suggestions of sexual dysfunction.

PMID- 16645679
TI  - [Weak or absent sexual sens towards the opposite sex, replaced by a sexual
      tendency towards the same sex (homosexual or inverted sens)].

PMID- 16645680
TI  - [Reporting on psychoanalytic clinic].
AB  - As mediation between absolute reserve (which is inherent in the psychoanalytic
      session) and communication of this experience to third parties (as supervisors,
      colleagues, public), psychoanalytic clinical accounts require and acquire a
      narrative procedure with its own specificity. So much so, that it can be said
      that this token consecrates a particular testimony as valid for scientific
      discussion. The present work makes reference to the moment in history since when
      Psychoanalysis departs from traditional psychiatry and progressively conquers an
      autonomy that dwells upon such procedure. The transmission in words, be it oral o
      written, of what went on during the sessions shares many common grounds with
      Literature. Regarding these, some points are raised as to the style that may be
      more germane to this purpose, and queries come up whether or not clinical
      accounts can ever enter the realm of letters as a literary subclass on its own.

PMID- 16645681
TI  - Bicycle protection laws in Singapore: are more compelling data still needed?

PMID- 16645682
TI  - Hermann von Helmholtz (1821-1894): inventor of the ophthalmoscope.

PMID- 16645683
TI  - Tocolytic treatment for the management of preterm labour: a systematic review.
AB  - Spontaneous preterm labour and delivery accounts for approximately one-third of
      preterm births, which is the predominant cause of perinatal mortality and
      morbidity. This review aims to evaluate the evidence on the benefits and harms of
      five classes of tocolytic therapy, namely: betamimetics, calcium channel
      blockers, magnesium, non-steroidal anti-inflammatory agents, and atosiban. We
      performed a systematic review of the effectiveness of tocolytics to stop uterine
      contractions (first-line therapy). Reports of randomised controlled trials from
      searches of MEDLINE, bibliographies of review articles, Cochrane Collaboration
      and its Pregnancy and Childbirth Review Group between 1966 and 2003 were
      identified, using the search terms "randomised controlled trial" (RCT), "preterm
      labor", "tocolysis", "betamimetics", "ritodrine", "prostaglandin synthetase
      inhibitors", "indomethacin", "calcium channel blockers", "nifedipine", "oxytocin
      receptor blockers", "atosiban", and "magnesium sulphate". Studies on women with
      preterm labour comparing the effects of a tocolytic with a placebo or no
      treatment that met our inclusion criteria, were included. To our knowledge, the
      trials were conducted mainly before 1999 and there were no placebo-controlled
      trials after that. Of the 86 articles identified and evaluated, 14 first-line
      studies met more stringent requirements for meta-analyses. Tocolytics were
      associated with significant decreases in the odds of delivery within 24 hours
      (odds-ratio [OR] 0.54, 95 percent confidence interval [CI] 0.32-0.91) and 48
      hours (OR 0.47, 95 percent CI 0.30-0.75). These effects were significant for beta
      agonists, atosiban and indomethacin, but not magnesium sulphate. Maternal side
      effects significantly associated with betamimetics were pulmonary oedema, cardiac
      arrhthymias and hypokalaemia. Although calcium antagonists have not been
      evaluated against placebo, comparative trials with beta-agonists have shown more
      favourable neonatal outcomes and better prolongation of gestation. In conclusion,
      the management of threatened preterm labour with first-line tocolytic therapy can
      prolong gestation. However, the time gained in-utero need to be optimised. There
      is no clear first-line tocolytic agent. The use of tocolytic agents should be
      individualised and based on maternal condition, potential side-effects and
      gestational age.

PMID- 16645684
TI  - Helmet use and bicycle-related trauma in patients presenting to an acute hospital
      in Singapore.
AB  - INTRODUCTION: To describe the relationship between bicycle helmet use and injury
      pattern sustained by patients presenting to an emergency department (ED) in
      Singapore for bicycle-related trauma. METHODS: Data was collected from all
      individuals treated for bicycle-related trauma between September 1, 2004 and May
      31, 2005 using a closed-ended questionnaire. RESULTS: 160 bicyclists with mean
      age of 34.4 years (range 10 to 89 years) were surveyed. Among them, 80 percent
      were male and 30.6 percent were non-residents. Helmets were worn by 10.6 percent
      of the patients. Alcohol was clinically detected in 11.3 percent of bicyclists.
      There was no difference in bicycle helmet use between Singaporeans and non
      residents (p-value is 0.275). However, compared to younger bicyclists, bicyclists
      aged 30 years or older (p-value is less than 0.05), and compared to recreational
      or sport bicyclists, those who commute by bicycle, tended not to wear helmets (p
      value is less than 0.01). Compared to Singaporeans (p-value is less than 0.05),
      non-residents and bicyclists aged 30 years or older (p-value is 0.011) believed
      that helmets did not protect against head injury. Comparing the helmeted group
      with the non-helmeted group, injury patterns by body region were: head injury 5.9
      percent versus 40.0 percent (p-value is less than 0.01); facial injury 5.9
      percent versus 37.1 percent (p-value is less than 0.05). Not wearing a helmet,
      being hit by a motor vehicle and age were significantly associated with higher
      injury severity scores, after adjusting for several potential confounding
      factors. CONCLUSION: Bicycle helmet use was low in our sample of injured
      patients. When worn, protection against injury was demonstrated. A campaign to
      promote use of bicycle helmets should be targeted at non-residents and older
      bicyclists. Authorities should consider compulsory helmet laws for bicyclists and
      expanding anti-drunk driving campaigns to target alcohol-intoxicated bicyclists.

PMID- 16645685
TI  - Heelys injuries in children.
AB  - INTRODUCTION: Heelys, a type of shoes with stealth wheels, are extremely popular
      among children in Singapore. The widespread availability of cheap imitations has
      led to a proliferation of young users. Coupled with a total lack of safety
      equipment and instructions, these shoes can lead to significant injuries. The
      purpose of this study was to examine the incidence and type of injuries sustained
      by children using Heelys. METHODS: During a seven-month period from February to
      August 2004, all children treated at the Paediatric Orthopaedic Department of the
      KK Women's and Children's Hospital, were asked if the injury was sustained while
      "heeling". All the patients were reviewed by the authors. A total of 37 patients
      with significant injuries sustained while "heeling" were identified. Their
      radiographs and clinical charts were reviewed. The patients and/or their parents
      were also interviewed to obtain additional information. RESULTS: Upper limb
      injuries were by far the most common. Distal radius fractures and elbow injuries
      predominated. None of the children used safety gear. CONCLUSION: "Heeling" can
      lead to serious injuries despite the relatively low velocity involved. Children
      and their parents need to be educated on the use of safety gear.

PMID- 16645686
TI  - Unintentional injuries in infants in Singapore.
AB  - INTRODUCTION: To describe the risk factors, causes and outcome of infant injuries
      so as to guide the formulation of injury prevention strategies specific for
      Singapore babies less than one year old. METHODS: Demographical, socio-economic
      data, and data on the circumstances of injury, nature, severity of injury and
      clinical outcome of all infants less than one year old and who sought medical
      attention for or died from unintentional childhood injuries or poisoning, at the
      Emergency Departments of three SingHealth hospitals, two SingHealth primary care
      polyclinics and the Forensic Medicine Department, Health Sciences Authority
      during a six-month period, were extracted from a larger Childhood Injuries
      Surveillance database and analysed. RESULTS: 405 cases of accidental injury and
      poisoning in infants aged less than one year were seen from February to July
      2002. 40.5 percent of injuries occurred when infants were left alone. Most
      infants were aged between nine months to one year (37 percent), male (57.3
      percent), first-born (57.3 percent) and Chinese (69 percent), with no past
      medical history (96.1 percent). 91 percent of the injuries occurred at home, of
      which 60.5 percent occurred in the bedroom. Falls were the major mechanism of
      injury (77 percent). A total of 431 injuries were sustained. 63 percent were head
      injuries - mainly stable head injuries, which made up 93.1 percent of all the
      head injuries. 67.5 percent of the cases were discharged without follow-up, while
      17.9 percent required hospital admission, mostly to the general ward (98.6
      percent of total admissions), and to the neurosurgery department (84.9 percent of
      total admissions). There were two fatalities in this study population. The
      mechanisms and patterns of injury changed with increasing motor ability of the
      infants. CONCLUSION: Parents and caregivers of infants should be taught and
      reminded about the age specific measures in injury prevention as their wards go
      through the various developmental stages in the first year of life. Emphasis
      should be placed on close caregiver supervision, identifying potential injury
      hazards in the home, fall prevention, adopting safe infant care practices and the
      safe use of infant care products.

PMID- 16645687
TI  - Percutaneous endoscopic gastrostomy outcomes: can patient profiles predict
      mortality and weaning?
AB  - INTRODUCTION: The benefits of percutaneous endoscopic gastrostomy (PEG) remain
      controversial. Patient selection is important to identify those who will benefit
      from PEG. This study aims to identify patient factors that may help in patient
      selection for PEG. METHODS: Patients who underwent PEG at the Gastroenterology
      Unit of Tan Tock Seng Hospital, Singapore, from January 1998 to December 1999,
      were identified. Multiple logistic regression was used to predict patient's
      outcomes. RESULTS: There were 106 (61 male) patients with a mean follow-up period
      of 465 days (range 3-1,410 days). The mean patient age was 64.5 years (range 17
      94 years). The 30-day, six-month, one-year and two-year mortality rates were 7.5
      percent, 26.4 percent, 35.8 percent and 46.2 percent, respectively. Older age (p
      value is 0.023), presence of bedsores (p-value is 0.042) and abnormal nutritional
      status based on body mass index less than 20 kg/square metres (p-value is 0.001)
      were predictive of mortality. 26 percent of patients were able to wean off PEG in
      an average period of 185 days (range 3-870 days). Patients were generally younger
      (p-value is 0.003) and had better renal function (p-value is 0.047). CONCLUSION:
      Older age, poor nutritional status and presence of bedsores were predictors of
      poor outcome. Younger age and preserved renal function were significant
      predictors of weaning off PEG feeding.

PMID- 16645688
TI  - Urological complications in renal transplantation.
AB  - INTRODUCTION: Renal transplantation has gained much wider acceptance as a
      treatment option for local patients with end-stage renal failure in the last
      three decades. However, there are no local reports regarding the associated
      urological complications and their management. This paper aims to explore these
      complications in the local setting. METHODS: This is a retrospective review of
      440 consecutive renal transplantations performed in Singapore General Hospital
      over a ten-year period. From the retrieved clinical records of transplant
      recipients, the occurrence of various urological complications and their
      management were studied. RESULTS: The overall incidence of urological
      complications among transplant recipients was 7.7 percent. Urological
      complications included urinary leakage, ureteric strictures, symptomatic
      lymphocoeles, malignancies, urolithiasis, double-J stent fragmentation as well as
      haemorrhagic cystitis, and their incidences were 1.4 percent, 2.0 percent, 1.8
      percent, 2.3 percent, 0.2 percent, 0.2 percent and 0.2 percent, respectively.
      Among the malignancies, 70 percent were renal cell carcinomas in the native
      kidneys. CONCLUSION: The incidence of urological complications in our series was
      comparable to those in the various major centres. However, there was a
      significantly higher incidence of native renal cell carcinoma in our series,
      which was likely to be secondary to the prolonged period of dialysis prior to
      renal transplantation.

PMID- 16645689
TI  - Risk factors for developing sleep-disordered breathing in patients with recent
      ischaemic stroke.
AB  - INTRODUCTION: There are several studies that reported a higher frequency of sleep
      disordered breathing (SDB) among ischaemic stroke patients with increasing
      evidence linking SDB and cardiovascular complications. Many showed prevalence
      between 43 percent and 72 percent, taking the apnoea-hypopnoea index (AHI) equal
      to or greater than ten. The main objective of this study was to determine the
      frequency of SDB in recent ischaemic stroke patients admitted to Hospital
      Universiti Kebangsaan Malaysia (HUKM) and the relationship between SDB and known
      risk factors of ischaemic stroke. METHODS: This was a cross-sectional,
      prospective study involving 28 consecutive acute ischaemic stroke patients
      admitted to HUKM over three months. Sleep studies were done within one to four
      weeks after stroke onset. Demographical data and associated risk factors were
      recorded and data were analysed. RESULTS: There were 20 men and eight women, with
      mean age of 60.3 +/- 8.9 years. There were eight Malay, 16 Chinese and four
      Indian patients. The prevalence of SDB in ischaemic stroke depending on the AHI
      cut-off was: 92.8 percent for AHI greater than or equal to five, 78.5 percent for
      AHI greater than or equal to ten, 44.5 percent for AHI greater than or equal to
      15, and 37.7 percent for AHI greater than or equal to 20. We discovered that
      diabetes mellitus and smoking history were important factors predicting
      significant SDB (AHI greater than or equal to 15) in recent ischaemic stroke
      cases. CONCLUSION: There was a high prevalence of SDB in recent ischaemic stroke
      patients in HUKM, comparable to other studies. Diabetes mellitus and smoking
      history were strong predictors of the occurrence of SDB after an ischaemic
      stroke.

PMID- 16645690
TI  - The prognostic value of tissue factor levels in acute ischaemic stroke.
AB  - INTRODUCTION: There is no biological marker that can accurately predict the
      prognosis after an acute ischaemic stroke. The main objective of this study was
      to evaluate the prognostic value of tissue factor (thromboplastin) levels in
      first ischaemic stroke. METHODS: This was a prospective study of all patients
      with first ischaemic stroke conducted from October 2003 to February 2004. Plasma
      for tissue factor levels was kept at -80 degrees Celsius and was analysed at the
      end of the study period by an independent person. The activities of daily living
      (ADL) were assessed by using the Barthel index (BI) on admission and at one month
      after the stroke onset. Any death or recurrent events were recorded. RESULTS: 50
      patients were recruited into the study. The median tissue factor level was 184.5
      +/- 97.3 pg/ml. Only age (p-value is 0.027) and middle cerebral artery (MCA)
      infarcts (p-value is 0.038) were found to be significant independent predictors
      for severe disability at one month with BI equal to or less than 9. There was no
      correlation of tissue factor level with BI at one month post-stroke (r equals 
      0.028, p-value is 0.846) and there was also no significant relationship between
      levels of tissue factor and recurrent events (p-value is 0.41). CONCLUSION: There
      is no correlation between tissue factor levels with acute ischaemic stroke
      outcome.

PMID- 16645691
TI  - Is there any effect of Ramadan fasting on stroke incidence?
AB  - INTRODUCTION: Over one billion Muslims fast worldwide during the month of
      Ramadan. Fasting during Ramadan is a radical change in lifestyle for the period
      of a lunar month. The objective of this study was to investigate whether Ramadan
      fasting has any effect on the incidence of stroke and its outcome in a
      geographically-defined population. METHODS: We retrospectively reviewed a 13-year
      stroke database and studied the data on Muslim patients who were hospitalised
      with stroke over a 13-year period from January 1991 to December 2003. Patients
      were divided according to the time of presentation in relation to the month of
      Ramadan, one month before, during, and one month after Ramadan. The number of
      hospitalisations for stroke in various time periods was analysed. The age of
      presentation, gender, cardiovascular risk factor profiles (smoking status,
      hypertension, hypercholesterolaemia, diabetes mellitus, and pre-existing
      cardiovascular disease) were analysed. We also studied the trends of in-hospital
      mortality, morbidity and acute medical care provided. RESULTS: Overall, 335
      Muslim patients were hospitalised for stroke. Their mean age and standard
      deviation were 56.99 and 13.9 years, respectively. The number of hospitalisations
      for stroke was not significantly different in the month of Ramadan (29 cases),
      when compared to the month before Ramadan (30 cases) and the month after Ramadan
      (29 cases). Risk factors included for stroke were not significantly different in
      Ramadan when compared to the month before and after Ramadan. These associated
      diseases were hypertension, diabetes mellitus, hypercholesterolaemia, acute
      myocardial infarction, and congestive heart failure. CONCLUSION: This study
      demonstrated that no significant difference was found in the number of
      hospitalisations for stroke while fasting during the month of Ramadan when
      compared to the non-fasting months.

PMID- 16645692
TI  - The changes of metabolic profile and weight during Ramadan fasting.
AB  - INTRODUCTION: Ramadan is the holiest month in the Islamic calendar and Muslims
      fast during this month. We designed this study to evaluate the effect of Ramadan
      fasting on plasma lipids and lipoproteins. METHODS: This cohort study was
      performed during Ramadan in December 2002 (Islamic year 1423). The subjects were
      81 students of Tehran University of Medical Sciences. We evaluated weight, body
      mass index (BMI), glucose, triglyceride (TG), cholesterol, low density
      lipoprotein (LDL), high density lipoprotein (HDL), and very low density
      lipoprotein (VLDL), before and after Ramadan. RESULTS: Body weight and BMI both
      decreased during Ramadan fasting in both genders. Glucose and HDL decreased and
      LDL increased significantly during fasting in Ramadan, but there was no
      significant change in total cholesterol, TG and VLDL. We did not find any
      association between TG, cholesterol, LDL, VLDL, HDL and the following variables:
      sex, body weight changes, and two or three instances of meals before Ramadan.
      Triglyceride level also increased in students with normal BMI while it decreased
      in overweight subjects. CONCLUSION: This study indicated that Ramadan fasting led
      to a decrease in glucose and weight. Although there was a significant reduction
      in meal frequency, a significant increase in LDL and decrease in HDL was noted
      during Ramadan. It seems that the effect of Ramadan fasting on serum lipid levels
      may be closely related to the nutritional diet or biochemical response to
      starvation.

PMID- 16645693
TI  - Foreign body aspiration in adults.
AB  - Foreign body aspiration is not an uncommon problem, particularly in children, the
      elderly, and those with predisposing factors like neurological impairment. In
      adults, regional differences exist in the type of foreign body aspirated. We
      report four cases of foreign body aspiration in South Asian adults, three of
      which were related to the widespread habit of chewing stimulant seeds such as
      betel nuts (two) and tamarind seed (one). It is important for clinicians to
      maintain a high index of suspicion for the diagnosis of foreign body inhalation
      in the appropriate clinical setting. Bronchoscopy is necessary not only for the
      diagnosis but also for the removal of foreign body from the bronchial tree. Once
      the foreign body is removed, the improvement in symptoms is usually dramatic,
      making it rewarding for any physician to manage.

PMID- 16645694
TI  - Primary anterior abdominal wall actinomycosis.
AB  - Actinomycosis of the anterior abdominal wall is rare. We report a 50-year-old
      diabetic man who presented with a left hypochondrial mass of three weeks duration
      associated with fever. Abdominal computed tomography showed a 2 x 4 cm mass
      projecting from the internal abdominal wall associated with surrounding
      inflammation. The mass did not decrease after a week of intravenous antibiotics.
      Excision of the mass and primary closure of the abdominal wall were performed.
      The mass involved the deep muscles of anterior abdominal wall. The omentum was
      adherent to the parietal peritoneum underneath the mass. Microscopical
      examination of the mass was consistent with actinomycosis. The postoperative
      period was uneventful and the patient recovered completely. The patient received
      penicillin for six months.

PMID- 16645695
TI  - Transient palsy of peripheral cranial nerves following open heart surgery.
AB  - A 32-year-old man developed hoarseness of voice, inability to swallow and
      restricted movement of the tongue after open heart surgery. Peripheral injury of
      the cranial nerves IX, X and XII was suspected, and it was thought that the
      duration of the surgery together with the endotracheal tube cuff and trans
      oesophageal echocardiography probe pressure, as well as the head and neck
      position might have been the causes of this complication.

PMID- 16645696
TI  - Clinics in diagnostic imaging (109). Nocardial adrenal abscess.
AB  - A 34-year-old man presented with a two-month history of intermittent fever and
      left loin pain. A large left suprarenal mass was detected on computed tomography
      and magnetic resonance imaging. Blood pressure, serum electrolytes, serum
      cortisol and urinary catecholamines were normal. Laparoscopic adrenalectomy was
      planned but the mass was found to be an isolated adrenal abscess due to
      Nocardiosis. He was later found to have AIDS. The clinical utility of various
      imaging modalities and management of adrenal cysts are reviewed.

PMID- 16645697
TI  - Electrocardiographical case. A young man with chest pain.
AB  - A 31-year-old Chinese man presented with complaint of acute chest pain. 12-lead
      electrocardiogram (ECG) showed sinus rhythm, with widespread upward concave ST
      segment elevations. The ECG changes along with a history of acute chest pain in a
      young man with minimal coronary risk factors are suggestive of acute
      pericarditis. He subsequently developed a pericardial effusion. Diagnosis,
      treatment and complications of acute percarditis are discussed.

PMID- 16645698
TI  - The early history of pharmacy in Singapore.

PMID- 16645699
TI  - Centennial Of Medical Education: jottings on the history of dentistry in
      Singapore.

PMID- 16645701
TI  - Dr Gwee Ah Leng, July 17, 1920 - March 31, 2006. A tribute to our first Editor.

PMID- 16645704
TI  - Cheek pouch use in relation to interspecific competition and predator risk for
      three guenon monkeys (Cercopithecus spp.).
AB  - Forest guenons (Cercopithecus spp.) are often found in polyspecific associations
      that may decrease predator risk while increasing interspecific competition for
      food. Cheek pouch use may mitigate interspecific competition and predator risk by
      reducing the time spent in areas of high competition/predator risk. I
      investigated these ideas in three forest guenons: Campbell's monkey
      (Cercopithecus campbelli), spot-nosed monkey (C. petaurista), and Diana monkey
      (C. diana). I present 13 months of scan sample data from Tai Forest, Cote
      d'Ivoire, including 3,675, 3,330, and 5,689 records of cheek pouch distention, to
      quantify cheek pouch use, for Campbell's, spot-nosed, and Diana monkeys,
      respectively. Cheek pouches are often used to hold fruit, so I first predicted
      that the most frugivorous species, Diana monkeys, would have the most cheek pouch
      distension. Spot-nosed monkeys ate the least amount of fruit over the study
      period and had the least distended cheek pouches, suggesting the importance of
      frugivory in relation to cheek pouch distension for this species. This was not a
      sufficient explanation for Campbell's monkeys; Campbell's ate fruit less than
      Diana monkeys, but had more distended cheek pouches, suggesting that cheek pouch
      use was not simply a reflection of high frugivory. From the interspecific
      competition hypothesis, I predicted that Campbell's monkeys would have more
      distended cheek pouches than Diana and spot-nosed monkeys, and more distended
      cheek pouches when associated with Diana because Campbell's monkeys have the
      highest potential for interspecific competition with dominant Diana monkeys. From
      the predator risk hypothesis, I predicted that Campbell's would have more
      distended cheek pouches when not associated with highly vigilant Diana monkeys.
      Campbell's monkeys had the most distended cheek pouches overall, but had more
      distended cheek pouches when not in association with Diana, suggesting the
      greater importance of predator risk rather than interspecific competition in
      Campbell's cheek pouch use.

PMID- 16645705
TI  - Influence of group size on reproductive success of female ring-tailed lemurs:
      distinguishing between IGFC and PFC hypotheses.
AB  - Based on data obtained over a period of 11 years from female ring-tailed lemurs
      (Lemur catta), we analyzed the correlation between group size and female
      reproductive parameters. The birth rate and mean number of surviving infants 1
      year after birth per adult female generated an inverted U-shaped curve when
      plotted against group size (although not significant) and number of adult female
      members. Infant mortality rate did not have a consistent correlation with group
      size and number of adult female members. Thus, our findings were similar to the
      predictions of Wrangham's inter-group feeding competition hypothesis.

PMID- 16645706
TI  - [Primary metastatic renal metastatic carcinoid tumor in a young male patient: a
      contribution to the differential diagnosis of neuroendocrine tumors].
AB  - Primary renal carcinoid tumors originating in normal kidney are extremely rare.
      We report a case of primary renal carcinoid tumor with an aggressive clinical
      course and multiple metastases in the paraaortal lymph nodes and the liver as
      well as a pulmonary metastasis, in a 30-year-old patient. A CT scan of the
      abdomen revealed a large mass in the right kidney and multiple tumor suspect
      areas in the liver and paraaortal lymph nodes. The patient did not have clinical
      manifestations of carcinoid syndrome. Histologically, the tumor was composed of
      trabecular, solid or anastomosing ribbon-like nests, identical to the features of
      neuroendocrine tumors from other locations. Immunohistochemical staining was
      positive for cytokeratin, neurospecific enolase, and chromogranin. Electron
      microscopically, tonofibrils, primitive desmosomes, and dense-core granules with
      a neuroendocrine appearance were present. The pathological features of this case
      are briefly reviewed in comparison with those of previously reportet in terms of
      certain clinical aspects, prognostic factors and the WHO-classification (2004) of
      this rare neoplasia.

PMID- 16645708
TI  - Intralenticular intraocular foreign body after stone impact: CT and US findings.
AB  - INTRODUCTION: Intraocular foreign body (IOFB) is a relatively common entity in
      emergency departments worldwide. Appropriate ocular assessment is mandatory if an
      intraocular foreign body is suspected because it is associated with an increased
      risk of endophtalmitis and a wide range of complications including hyphaema,
      cataract, vitreous hemorrhage, and retinal tears and detachment. CASE REPORT: We
      present a case of intralenticular intraocular foreign body after stone impact.
      DISCUSSION: Ultrasonography (US) and computed tomography (CT) show an accurate
      location of the foreign body inside the lens. This finding enabled the surgeon to
      perform a phacoemulsification lens extraction with removal of the foreign body,
      the optimal method of removing intralenticular IOFB. To our knowledge, this is
      the first US and CT imaging report.

PMID- 16645710
TI  - Radical surgery after chemotherapy: a new therapeutic strategy to envision in
      grade II glioma.
AB  - While surgery is proned in low-grade glioma (LGG), the invasion of functional
      areas frequently prevents a complete resection. We report the first case of a
      patient operated on for a left frontal LGG, diagnosed because of seizures, with
      partial resection due to an invasion of the controlateral hemisphere.
      Chemotherapy enabled a regression of this controlateral extension.
      Postchemotherapy surgery performed with intraoperative functional mapping then
      allowed a complete resection, without sequelae. The patient has a normal socio
      professional life, with no seizure. No other treatment was given. There was no
      recurrence, with a follow-up of 2 years since the second surgery (3.5 years since
      the first symptom). We propose a new therapeutic strategy in unresectable LGG,
      with preoperative chemotherapy, to make a radical surgery possible in a second
      step, while preserving the quality of life.

PMID- 16645711
TI  - Development and rapid growth of a desmoid tumor in the surgical corridor after
      suboccipital craniotomy for recurrent low-grade astrocytoma.
AB  - Desmoid tumors are histologically benign but locally invasive tumors that can
      occur in the head and neck. We present the rare case of a desmoid tumor that
      occurred in the surgical corridor after suboccipital craniotomy for recurrent low
      grade astrocytoma. A 30-year-old woman underwent a repeat suboccipital craniotomy
      for recurrent low-grade astrocytoma. A gross total resection was achieved. Nine
      months later, a firm, palpable mass was noted near the surgical scar. No new
      neurologic deficits were noted on exam. A magnetic resonance imaging scan
      demonstrated a homogeneously enhancing lesion superficial to the dural graft.
      Surgical resection of the lesion was performed through the original midline
      incision. The mass was resected en bloc. Histology demonstrated clear surgical
      margins and a tumor of low cellularity consistent with a desmoid tumor. Desmoid
      tumors should be considered in the differential diagnosis for superficial masses
      occurring in the surgical bed after posterior cervical surgery.

PMID- 16645712
TI  - A case of neurolymphomatosis involving cranial nerves: MRI and fusion PET-CT
      findings.

PMID- 16645713
TI  - Isolated recurrence of intracerebral granulocytic sarcoma in acute lymphoblastic
      leukemia: a case report.
AB  - Intracranial granulocytic sarcoma (chloroma) may occur rarely in leukemia. A 27
      year-old male presented with an isolated recurrence of granulocytic sarcoma
      manifesting as an intraaxial mass 27 months after complete remission of acute
      lymphoblastic leukemia. He was admitted due to a severe headache and blurred
      vision. Brain magnetic resonance imaging demonstrated an enhanced mass which was
      initially interpreted as an extraaxial tumor in the right temporal region.
      Because of increased intracranial pressure and the mass effect, open biopsy with
      surgical resection was performed. The biopsy result indicated that intraaxial
      lymphoblastic leukemia infiltration had caused CNS relapse. Although granulocytic
      sarcoma occurs primarily in patients with acute myelogenous leukemia, the authors
      report a rare case of intraparenchymal granulocytic sarcoma in acute
      lymphoblastic leukemia.

PMID- 16645714
TI  - Complications of a temozolomide overdose: a case report.
AB  - PURPOSE AND BACKGROUND: This is a report of a 53 year-old man with a glioblastoma
      multiforme (GBM) treated with an excessive dose of temozolomide (TMZ). METHODS:
      This is a single case review of all clinically relevant records. O6-methylguanine
      DNA methyltransferase activity was determined by a biochemical assay. RESULTS:
      Following conventional radiotherapy (RT) without concurrent chemotherapy, the
      patient received 5,500 mg of TMZ over 2 days. At the standard dose of 200
      mg/m2/day his total 5-day dose should have been 1,940 mg. Acutely he had nausea,
      vomiting and diarrhea for 2 days which cleared. The dominant severe toxicity was
      pancytopenia between one and four weeks after TMZ which was complicated by
      secondary infections that were successfully managed. Transient transaminitis
      occurred but there were no significant pulmonary, renal or other systemic
      toxicities. His progression free survival was 22 months and overall survival 24
      months. CONCLUSION: His outcome suggests that TMZ may prove to be a good agent
      for dose-escalation trials with hematopoietic stem cell rescue.

PMID- 16645715
TI  - Radiotherapy plus concomitant and adjuvant temozolomide for leptomeningeal
      pilomyxoid astrocytoma: a case study.

PMID- 16645716
TI  - Gemistocytes in astrocytomas: are they a significant prognostic factor?
AB  - Our aim was to retrospectively evaluate the influence of gemistocytic astrocytes,
      cellular proliferation indices, immunoexpression of proteins p53 and bcl-2 in the
      clinical outcome of 39 patients with WHO grade II and III astrocytomas with the
      presence of gemistocytes. The mean proportion of gemistocytes was 18.7% and the
      mean proliferative index was 3.3%. Immunoexpression of p53 was detected in 29
      cases (74.4%) and all cases (100%) were positive for bcl-2. The median overall
      survival was 97.2 months and the progression-free survival was 43.1 months.
      Estimated 1-, 5- and 10-year overall survival rates were 94.3%, 69.5% and 46.4%;
      1-, 5- and 10-year progression-free survival rates were 91.1%, 26.1% and 13.1%.
      Out of 24 who presented clinical and neuroimaging worsening, characterized as
      tumor progression or recurrence, 16 had histological confirmation and were also
      analyzed. We could not detect significant differences when comparing all the
      indices between WHO grade II and III and also between the first and second
      biopsies. We also could not detect significant differences in progression-free
      and overall survival when analyzing the gemistocyte index and the
      immunohistochemical labeling indices p53, bcl-2 and MIB-1, as well as patientsa9
      age (median value, up to 34 vs. over 34 years) and histological grade (II or
      III). Our finding confirms recent reports that question the role of gemistocytes
      as a prognostic factor in diffuse astrocytomas. The significance and role of
      gemistocytes in astrocytomas has yet to be defined and warrants further study.

PMID- 16645717
TI  - Surgical treatment for severe visual compromised patients after pituitary
      apoplexy.
AB  - BACKGROUND: Pituitary apoplexy is a rare neurovascular insult. Early surgical
      decompression is the most effective treatment, especially for rapid deterioration
      of visual acuity or for altered consciousness. The timing of rapidly expanded
      mass was strongly related to the treatment outcome. METHODS: Thirteen patients
      who presented with severe visual defect after pituitary apoplexy were enrolled
      retrospectively. Six patients without severe underlying diseases were considered
      non-complicated and were treated early. Another seven patients who received
      delayed treatment after medical problems were stabilized and/or conservative
      management failed were considered to be complicated. The visual acuity of each
      individual eye was evaluated and organized into six grades based on visual
      acuity. Twelve patients received transsphenoidal surgery and one craniotomy was
      performed for tumor removal. RESULTS: The delay of surgical treatment was 3.5
      days and 8.7 days in the two groups, respectively. Overall, 19 out of 26 eyes
      (73%) improved after surgery; 100% in non-complicated group and 50% in
      complicated group. The average grade of visual improvement was 2.66 vs. 0.71 by
      each individual eye, and the difference was statistically significant (P<0.000).
      The ratio of regained useful vision was significant in non-complicated patients
      (P<0.000). The incidence of requirement long-term hormone replacement was high in
      the complicated group (2/6 vs. 6/7). The resection rate was total in 8 patients,
      subtotal in 3, partial in 1, with one loss of image follow-up. CONCLUSIONS: Early
      decompression significantly improved visual outcomes and the need for hormone
      replacement was minimal. We postulated old age, underlying malignant diseases,
      and coagulation disorders played the predisposing factors of poor outcome in
      these cases.

PMID- 16645718
TI  - Maintenance treatment with interferon-gamma and low-dose cyclophosphamide for
      pediatric high-grade glioma.
AB  - BACKGROUND: The prognosis of high-grade glioma in children is poor. PURPOSE:
      Interferon-gamma may increase the immune surveillance of glioma cells. Earlier
      clinical evidence had shown that low dose cyclophosphamide (CPM) increased immune
      response. METHODS: After induction treatment with simultaneous radiation and
      chemotherapy, patients were treated with individually increasing interferon-gamma
      (IFN-gamma) doses starting from 25 microg/m2/d s.c. increasing up to a maximum of
      175 microg/m2/d within 7 weeks. Cyclophosphamide was given at 300 mg/m2 i.v.
      every 21 days. Forty pediatric glioma patients were enrolled (median age: 8.5
      year, male: n = 22). Tumor locations included cerebral cortex (n = 8), basal
      ganglia (n = 4), brainstem (n = 24), cerebellum (n = 3), spinal cord (n = 1).
      Histologies were GBM (n = 14), AA (n = 14), LGG (n = 2, diffuse intrinsic pontine
      glioma). There was grade IV toxicity for thrombocytopenia (10%) and leucopenia
      (2.5%), grade III toxicity for central nervous (2.5%) and hepatic (5%) side
      effects, no toxic death. The observation time of the six surviving patients was:
      1.2, 1.9, 4.2, 4.4, 4.6 and 4.7 years respectively. The median overall survival
      (1 year) was not significantly different from a historical control group (0.8
      years). The survival of pontine gliomas appeared even inferior when compared to
      the previous protocol (n.s.). CONCLUSION: Maintenance treatment with IFN-gamma
      and low dose CPM has no sufficient beneficial effect for the treatment of high
      grade glioma.

PMID- 16645719
TI  - Glioblastoma multiforme of the pineal region.
AB  - Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal
      region. We present three cases in which patients presented with a
      pineal/posterior third ventricular region mass and review all the previously
      reported cases in the literature. Pineal region GBM seems to be a very aggressive
      tumor with a high rate of leptomeningeal and ependymal metastatic disease.
      Patients usually present with signs and symptoms of hydrocephalus and Parinaud's
      syndrome. The clinical and radiological characteristics of pineal GBM do not
      differentiate it from other malignancies of this region, thus surgical biopsy is
      generally required for definitive diagnosis. Glioblastoma should be considered in
      the differential diagnosis of the pineal region tumors, especially when evidence
      of leptomeningeal or ependymal metastatic disease is present.

PMID- 16645720
TI  - Carboplatin and etoposide (CE) chemotherapy in patients with recurrent or
      progressive oligodendroglial tumors.
AB  - BACKGROUND: Oligodendroglial tumors are rare and chemosensitive diseases; but the
      overall results with current chemotherapy regimens cannot be considered
      satisfactory and other active treatments are necessary. We decided to determine
      the efficacy and toxicity profile of the carboplatin and etoposide (CE) regimen
      in this setting. METHODS: In this phase II trial we evaluated the response rate
      of first or second line CE regimen (Carboplatin AUC 5 on day 1 and Etoposide 120
      mg/m2 on days 1-3 every 28 days) in patients with recurrent/progressive
      oligodendroglial tumors. RESULTS: Thirty-two patients were enrolled. Median age
      was 42 years (range 22-66); median ECOG PS was 0 (range 0-2); 9 patients had
      oligodendroglioma, 3 patients had oligoastrocytoma, 11 patients had anaplastic
      oligodendroglioma, 9 patients had anaplastic oligoastrocytoma. CE regimen showed
      a response rate of 46.9% with 5 complete responses (15.6%) and 10 partial
      responses (31.3%). Eleven patients (34.4%) had stable disease. Median time to
      progression was 8 months, progression-free survivals at 6 and 12 months were 80%
      and 46.9%, respectively. Toxicity was mainly hematological, with grade 3-4
      neutropenia in 5 (15.6%) patients. CONCLUSIONS: In this trial CE regimen has
      shown relevant activity with a favourable safety profile.

PMID- 16645721
TI  - Gene expression profiles of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2
      chloroethyl)-3-nitrosourea (ACNU)-resistant C6 rat glioma cells.
AB  - Chemotherapy in itself is suspected to cause the development or selection of drug
      resistant tumor cells, which have more aggressive phenotypes. The authors
      investigated the differential changes of gene expression in the 1-(4-amino-2
      methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant
      subline of the C6 rat glioma (C6AR2), which was established from C6 rat glioma
      cells by exposure to ACNU in vitro. The resistance to ACNU of C6AR2 was confirmed
      by MTS assay. The increased expression of O6-methylguanine-DNA methyltransferase
      in C6AR2 cells was shown using RT-PCR. C6AR2 cells displayed a higher
      proliferative activity relative to C6 cells. Analysis with cDNA array showed that
      19 genes were transcriptionally up-regulated and 16 genes down-regulated in C6AR2
      cells compared to C6 cells. They belonged to various functional classes of genes
      beside the drug-resistant system. Among them, the down-regulation of several
      genes in C6AR2 cells, including c-kit, pleiotrophin, platelet-derived growth
      factor receptor-alpha, peripheral myelin protein-22 and NG2 chondroitin sulfate
      proteoglycan, which are expressed originally in developmental glial lineages,
      were verified using semi-quantitative RT-PCR. In addition, the gene expression of
      astroglial intermediate filament proteins, including GFAP, vimentin and nestin,
      were decreased in C6AR2 cells relative to C6 cells in semi-quantitative RT-PCR
      and immunocytochemistry. These findings may represent an undifferentiated state
      of ACNU-resistant glioma cells and a more aggressive phenotype in recurrent
      tumors following chemotherapy.

PMID- 16645722
TI  - Suberoylanilide hydroxamic acid is effective in preclinical studies of
      medulloblastoma.
AB  - PURPOSE: Suberoylanilide hydroxamic acid (SAHA) has been studied in adult solid
      and hematologic malignancies. However, little information has been reported on
      the effects of SAHA on central nervous system (CNS) tumors including
      medulloblastoma, the most common malignant brain tumor in children. We
      investigated SAHA in preclinical medulloblastoma models to determine its anti
      cancer efficacy as well as its ability to affect intracranial lesions when
      administered systemically. EXPERIMENTAL DESIGN AND RESULTS: Tissue culture
      studies were performed treating primary human fibroblasts, established
      medulloblastoma cell lines, and primary human medulloblastoma tumors with SAHA.
      At 10 microM concentration, SAHA had little effect on normal fibroblasts but
      caused >90% apoptosis in cultured medulloblastoma cells. Primary medulloblastomas
      from patients were sensitive to SAHA compared to vehicle alone in ex vivo
      studies. In athymic mice with medulloblastoma xenograft tumors, oral SAHA
      resulted in apoptosis of tumor tissue and significantly slowed tumor growth. In
      the ND2:Smo transgenic mouse medulloblastoma model, SAHA treatment caused
      significant apoptosis in these cerebellar tumors. CONCLUSIONS: SAHA effectively
      induces cell death in established medulloblastoma cell lines, human patient
      primary tumor cultures, medulloblastoma xenografts and intracranial spontaneous
      medulloblastomas. Fibroblasts in culture and mice treated with SAHA did not
      reveal prohibitive toxicity profiles. These findings support the advancement of
      SAHA to pediatric clinical trials.

PMID- 16645723
TI  - Extraneural metastasis in intracranial tumors in children: the experience of a
      single center.
AB  - Our aim is to evaluate the clinical features and outcomes of children with
      primary central nervous system (CNS) tumors who develop extraneural metastasis
      (ENM). We retrospectively evaluated children diagnosed with primary CNS tumors
      treated at our institution between 1972 and 2004. Of 1,011 patients these tumors,
      10 (0.98%) developed ENM. The histopathologic diagnosis was medulloblastoma in
      six patients, germ cell tumors in two patients, and ependymoma and atypical
      teratoid rhabdoid tumor (ATRT) in one patient each. In six patients, the primary
      tumor was located in the posterior fossa; it had a supratentorial location in the
      patient with ATRT, was located in the sellar and suprasellar region in the two
      patients with germ cell tumors, and was found in the distal spinal cord in the
      patient with an ependymoma. In two patients ENM was detected at the time of
      diagnosis. In other patients ENM developed between 9 and 25 months after
      diagnosis. Metastatic sites included bone, bone marrow, lung, cervical lymph
      nodes, liver, and paranasal sinuses. Of the 10 patients who developed ENM, 8 died
      of their disease 0.27-16.2 months (median, 2.60 months) after it was detected.
      One patient with dysgerminoma is alive, without disease, 117.80 months after
      diagnosis of the ENM. One patient with germ cell tumor is alive with disease 11.3
      months after diagnosis of the ENM. Systemic metastasis to other extraneural sites
      is extremely rare in children with intracranial tumors. In our series the rate of
      ENM is 0.98%. The liver and lung are the most common site for metastasis,
      followed by the bone and bone marrow. The outcome is poor in patients with CNS
      tumors with ENM.

PMID- 16645724
TI  - Involvement of nuclear factor of activated T cells 3 (NFAT3) in cyclin D1
      induction by B[a]PDE or B[a]PDE and ionizing radiation in mouse epidermal Cl 41
      cells.
AB  - The results from animal studies have shown that mouse skin is highly susceptible
      to both ionizing radiation and benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE).
      Previous studies have also indicated that cyclin D1 plays a crucial role in
      controlling cell proliferation and tumorigenesis. We, therefore, investigated
      here the effect of ionizing radiation and B[a]PDE on cyclin D1 transcription and
      potential involvement of NFAT3 in regulation of cyclin D1 transcription in mouse
      epidermal Cl 41 cells. We found that B[a]PDE exposure induced a high level of
      NFAT activation and cyclin D1 transcription in mouse epidermal Cl 41 cells.
      Ionizing radiation exhibited an enhancement for NFAT activation and cyclin D1
      induction by B[a]PDE, even though ionizing radiation by itself had only a
      marginal effect. By stably knockdown of NFAT3 protein expression using specific
      NFAT3 small interfering RNA (siRNA), we found that cyclin D1 induction by B[a]PDE
      or B[a]PDE plus ionizing radiation was dramatically impaired. These results
      indicate that ionizing radiation is able to enhance cyclin D1 transcription
      induced by B[a]PDE, and NFAT3 is involved in the regulation of cyclin D1
      transcription by B[a]PDE or B[a]PDE plus ionizing radiation.

PMID- 16645725
TI  - Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in
      prostate cancer cells (PC-3).
AB  - BACKGROUND: Cancer metastasis, involving multiple processes and various
      cytophysiological changes, is a primary cause of cancer death and may complicate
      the clinical management, even lead to death. Quercetin is a flavonoid and widely
      used as an antioxidant and recent studies have revealed its pleiotropic
      anticancer and antiproliferative capabilities. Gelatinases A and B
      (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion
      and metastases. In this study, we observed the precise involvement of quercetin
      role on these proteinases expression and activity. DESIGN AND METHODS: PC-3 cells
      were treated with quercetin at various concentrations (50 and 100 microM), for 24
      h period and then subjected to western blot analysis to investigate the impact of
      quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions.
      Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected
      to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin
      zymography was also performed in quercetin treated PC-3 cells. RESULTS: The
      results showed that quercetin treatment decreased the expressions of MMP-2 and
      MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in
      the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory
      role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed
      the decreased activities of MMP-2 and MMP-9 in quercetin treated cells.
      CONCLUSION: Hence, we speculated that inhibition of metastasis-specific MMPs in
      cancer cells may be one of the targets for anticancer function of quercetin, and
      thus provides the molecular basis for the development of quercetin as a novel
      chemopreventive agent for metastatic prostate cancer.

PMID- 16645726
TI  - Characterization of a BODIPY-labeled fluorescent fatty acid analogue. Binding to
      fatty acid-binding proteins, intracellular localization, and metabolism.
AB  - The BODIPY-labeled fatty acid analogues are a useful addition to the tools
      employed to study the cellular uptake and metabolism of lipids. In this study, we
      show that BODIPY FL C(16) binds to purified liver and intestinal fatty acid
      binding proteins with high affinity at a site similar to that for the
      physiological fatty acid oleic acid. Further, in human intestinal Caco-2 cells
      BODIPY FL C(16) co-localizes extensively with mitochondria, endoplasmic
      reticulum/Golgi, and L-FABP. Virtually no esterification of BODIPY FL C(16) was
      observed under the experimental conditions employed. We conclude that BODIPY FL
      C(16) may be a useful tool for studying the distribution and function of FABPs in
      a cellular environment.

PMID- 16645727
TI  - Third promoter and differential regulation of mouse and human fatty acid
      translocase/CD36 genes.
AB  - Fatty acid translocase (FAT)/CD36 is a multi-functional membrane protein
      participating in uptake of long-chain fatty acids and oxidized low density
      lipoprotein, playing an important role in lipid homeostasis. We reported the dual
      promoter structures of the mouse and human FAT/CD36 genes in relation to the
      tissue-specific expression and regulation by peroxisome proliferator-activated
      receptors (PPARs) (Sato et.al. J. Biol. Chem. 277, 15703-15711, 2002). However,
      these structures alone could not explain a large induction of the mRNA by a PPAR
      ligand in the mouse intestine. To learn more about the tissue-specific
      transcriptional regulation of the FAT/CD36 gene for lipid homeostasis at the
      whole body level, we cloned the cDNA for the induced mRNA in the mouse intestine
      and identified third promoter close to the first common exon of the gene. The
      human gene also has essentially the same gene organization. RT-PCR and Northern
      blot analyses showed that the three promoters are differentially used in various
      mouse tissues and the cultured human cells. The physiological significance of
      these complex promoter structures was suggested by the differential
      responsiveness to a peroxisome proliferator-activated receptor ligand and the
      differences in translational efficiencies or stabilities of the mRNA among the
      isoforms.

PMID- 16645728
TI  - Thiamine attenuates the hypertension and metabolic abnormalities in CD36
      defective SHR: uncoupling of glucose oxidation from cellular entry accompanied
      with enhanced protein O-GlcNAcylation in CD36 deficiency.
AB  - BACKGROUND AND OBJECTIVES: The spontaneous hypertensive rat (SHR) is a widely
      studied model of hypertension that exhibits metabolic abnormalities, which share
      features with the human metabolic syndrome. Genetic linkage studies have revealed
      a defective CD36 gene, encoding a membrane fatty acid (FA) transporter, in
      hyperinsulinemia of the SHR. However, there is no unifying mechanism that can
      explain these phenotypes as a consequence of a defective CD36 gene. Impaired
      fatty acid uptake is compensated by increased glucose uptake. We hypothesized
      that (1) the abundant intracellular glucose is not oxidized proportionally and
      (2) the correction of the uncoupling of glucose oxidation to its cellular entry
      might be effective against the pathophysiology of CD36-defective SHR. Therefore,
      we attempted to activate glucose oxidation with the repletion of thiamine, a
      coenzyme for multiple steps of glucose metabolism. METHODS AND RESULTS: In one
      series of experiments, intracellular glucose fate was assessed by the ratio of
      [(14)C]glucose/[(3)H]deoxyglucose radioactivity, which suggested that glucose
      oxidation was uncoupled from its cellular entry in SHR. Protein O-GlcNAcylation
      was intense in the hearts of CD36-defective SHR compared with that of wild-type
      CD36 rats [Wister Kyoto rats (WKY)], indicating the shunt of glucose through the
      hexosamine biosynthetic pathway (HBP). In another series of studies, 4-week-old
      SHR were maintained with water containing 0.2% thiamine for 10 weeks. Systolic
      blood pressure, plasma insulin and norepinephrine levels were significantly lower
      in the thiamine-group, as compared with the untreated-group. In epididymal
      adipose tissue, thiamine repletion down-regulated the expression levels of mRNA
      transcripts for UDP-N-acetylglucosamine:peptide glycosyltransferase,
      angiotensinogen, angiotensin type 1 receptor, transforming growth factor-beta1
      and plasminogen activator inhibitor-1. CONCLUSIONS: The hearts of CD36-defective
      SHR exhibited uncoupling of glucose oxidation from its cellular entry,
      accompanied with the enhanced protein O-GlcNAcylation, suggesting increased
      glucose shunt through the HBP. Thiamine repletion in CD36-defective SHR resulted
      in (1) the correction of the uncoupling of glucose oxidation to its cellular
      entry, concomitant with reduced protein O-GlcNAcylation, (2) the down-regulation
      of the expression of mRNAs involved in HBP, the renin-angiotensin system and
      adipokines in epididymal adipose tissue, and (3) the attenuation of the
      hypertension and hyperinsulinemia. We propose that interventions targeting
      glucose oxidation with thiamine repletion may provide a novel adjunctive approach
      to attenuate metabolic abnormalities and related hypertension.

PMID- 16645729
TI  - Comparative antioxidant activity of tocotrienols and the novel chromanyl
      polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells.
AB  - Oxidative stress plays a pivotal role in the pathogenesis of several chronic
      diseases and antioxidants may represent potential tools for the prevention of
      these diseases. Here, we investigated the antioxidant efficiency of different
      tocotrienol isoforms (alpha-, delta-, gamma-tocotrienols), and that of FeAox-6, a
      novel synthetic compound which combines, by a stable covalent bond, the chroman
      head of vitamin E and a polyisoprenyl sequence of four conjugated double bonds
      into a single molecule. The antioxidant efficiency was evaluated as the ability
      of the compounds to inhibit lipid peroxidation, reactive oxygen species (ROS)
      production, heat shock protein (hsp) expression in rat liver microsomal membranes
      as well as in RAT-1 immortalized fibroblasts challenged with different free
      radical sources, including 2,2'-azobis(2-amidinopropane) (AAPH), tert-butyl
      hydroperoxide (tert-BOOH) and H2O2. Our results show that individual tocotrienols
      display different antioxidant potencies. Irrespective of the prooxidant used, the
      order of effectiveness was:delta-tocotrienol > gamma-tocotrienol = alpha
      tocotrienol in both isolated membranes and intact cells. This is presumably due
      to the decreased methylation of delta-tocotrienol chromane ring, which allows the
      molecule to be more easily incorporated into cell membranes. Moreover, we found
      that FeAox-6 showed an antioxidant potency greater than that of delta
      tocotrienol. Such an efficiency seems to depend on the concomitant presence of a
      chromane ring and a phytyl chain in the molecule, which because of four
      conjugated double bonds, may induce a greater mobility and a more uniform
      distribution within cell membrane. In view of these results, FeAox-6 represents a
      new potential preventive agent in chronic diseases in which oxidative stress
      plays a pathogenic role.

PMID- 16645738
TI  - Optical recording of electrical activity.

PMID- 16645739
TI  - Nano to micro -- fluorescence measurements of electric fields in molecules and
      genetically specified neurons.
AB  - Our central nervous system is based on the generation and propagation of
      electrical signals along the neuronal pathways. These variations of the membrane
      potential are arranged by the concerted action of ion channels in the neuronal
      membrane. Therefore, the exact measurement of the electric field in the central
      nervous system is the focus of intensive investigation. While
      electrophysiological methods provide exact measurements on the single-cell or
      single-molecule level with high temporal resolution, they are limited in their
      spatial resolution ranging from a few single cells to a single molecule. To
      thoroughly understand how the voltage-dependent ion channels sense the membrane
      potential and are precisely gated by it, the electric field within the protein
      has to be investigated. Likewise, the propagation of electrical impulses in a
      network of neurons involves a large number of cells, which have to be monitored
      simultaneously. For these endeavors, optical methods have proven to be useful due
      to their scalability, temporal and spatial resolution. Here, we will summarize
      the properties of the optical probes that we used to determine the electrical
      field strength within voltage-sensitive ion channels and discuss the hybrid
      approach to detect membrane potential changes in genetically specified neurons in
      terms of design, limitations and future developments.

PMID- 16645740
TI  - Wavelength- and time-dependence of potentiometric non-linear optical signals from
      styryl dyes.
AB  - Second harmonic generation (SHG) imaging microscopy is an important emerging
      technique for biological research, complementing existing one- and two-photon
      fluorescence (2PF) methods. A non-linear phenomenon employing light from mode
      locked Ti:sapphire or fiber-based lasers, SHG results in intrinsic optical
      sectioning without the need for a confocal aperture. Furthermore, as a second
      order process SHG is confined to loci lacking a center of symmetry, a constraint
      that is readily satisfied by lipid membranes with only one leaflet stained by a
      dye. Of particular interest is "resonance-enhanced" SHG from styryl dyes in
      cellular membranes and the possibility that SHG is sensitive to transmembrane
      potential. We have previously confirmed this, using simultaneous voltage-clamping
      and non-linear imaging of cells to find that SHG is up to four times more
      sensitive to potential than fluorescence. In this work, we have extended these
      results in two directions. First, with a range of wavelengths available from a
      mode-locked Ti:sapphire laser and a fiber-based laser, we have more fully
      investigated SHG and 2PF voltage-sensitivity from ANEP and ASTAP chromophores,
      obtaining SHG sensitivity spectra that are consistent with resonance
      enhancements. Second, we have modified our system to coordinate the application
      of voltage-clamp steps with non-linear image acquisition to more precisely
      characterize the time dependence of SHG and 2PF voltage sensitivity, finding
      that, at least for some dyes, SHG responds more slowly than fluorescence to
      changes in transmembrane potential.

PMID- 16645741
TI  - Changes in FAD and NADH fluorescence in neurosecretory terminals are triggered by
      calcium entry and by ADP production.
AB  - We measured changes in the intrinsic fluorescence (IF) of the neurosecretory
      terminals of the mouse neurohypophysis during brief (1-2 s) trains of stimuli.
      With fluorescence excitation at either 350 +/- 20 or 450 +/- 50 nm, and with
      emission measured, respectively, at 450 +/- 50 or > or = 520 nm, DeltaF/F(o) was
      approximately 5-8 % for a 2 s train of 30 action potentials. The IF changes
      lagged the onset of stimulation by approximately 100 ms and were eliminated by 1
      microM tetrodotoxin (TTX). The signals were partially inhibited by 500 microM
      Cd(2+), by substitution of Mg(2+) for Ca(2+), by Ca(2+)-free Ringer's with 0.5 mM
      EGTA, and by 50 microM ouabain. The IF signals were also sensitive to the
      mitochondrial metabolic inhibitors CCCP (0.3 microM), FCCP (0.3 microM), and
      NaN(3) (0.3 mM), and their amplitude reflected the partial pressure of oxygen
      (pO(2)) in the bath. Resting fluorescence at both 350 nm and 450 nm exhibited
      significant bleaching. Flavin adenine dinucleotide (FAD) is fluorescent, while
      its reduced form FADH(2) is relatively non-fluorescent; conversely, NADH is
      fluorescent, while its oxidized form NAD is non-fluorescent. Thus, our
      experiments suggest that the stimulus-coupled rise in [Ca(2+)](i) triggers an
      increase in FAD and NAD as FADH(2) and NADH are oxidized, but that elevation of
      [Ca(2+)](i), alone cannot account for the totality of changes in intrinsic
      fluorescence.

PMID- 16645742
TI  - Properties of new, long-wavelength, voltage-sensitive dyes in the heart.
AB  - Membrane potential measurements using voltage-sensitive dyes (VSDs) have made
      important contributions to our understanding of electrophysiological properties
      of multi-cellular systems. Here, we report the development of long wavelength
      VSDs designed to record cardiac action potentials (APs) from deeper layers in the
      heart. The emission spectrum of styryl VSDs was red-shifted by incorporating a
      thienyl group in the polymethine bridge to lengthen and retain the rigidity of
      the chromophore. Seven dyes, Pittsburgh I to IV and VI to VIII (PGH I-VIII) were
      synthesized and characterized with respect to their spectral properties in
      organic solvents and heart muscles. PGH VSDs exhibited 2 absorption, 2 excitation
      and 2 voltage-sensitive emission peaks, with large Stokes shifts (> 100 nm).
      Hearts (rabbit, guinea pig and Rana pipiens) and neurohypophyses (CD-1 mice) were
      effectively stained by injecting a bolus (10-50 microl) of stock solution of VSD
      (2-5 mM) dissolved in in dimethylsulfoxide plus low molecular weight Pluronic
      (16% of L64). Other preparations were better stained with a bolus of VSD (2-5 mM)
      Tyrode's solution at pH 6.0. Action spectra measured with a fast CCD camera
      showed that PGH I exhibited an increase in fractional fluorescence, DeltaF/F =
      17.5 % per AP at 720 nm with 550 nm excitation and DeltaF/F = - 6% per AP at 830
      nm with 670 nm excitation. In frog hearts, PGH1 was stable with approximately 30%
      decrease in fluorescence and AP amplitude during 3 h of intermittent excitation
      or 1 h of continuous high intensity excitation (300 W Xe-Hg Arc lamp), which was
      attributed to a combination of dye wash out > photobleaching > dynamic damage >
      run down of the preparation. The long wavelengths, large Stokes shifts, high
      DeltaF/F and low baseline fluorescence make PGH dyes a valuable tool in optical
      mapping and for simultaneous mapping of APs and intracellular Ca(2+).

PMID- 16645743
TI  - Optical imaging and functional characterization of the transverse tubular system
      of mammalian muscle fibers using the potentiometric indicator di-8-ANEPPS.
AB  - Potentiometric dyes are useful tools for studying membrane potential changes from
      compartments inaccessible to direct electrical recordings. In the past, we have
      combined electrophysiological and optical techniques to investigate, by using
      absorbance and fluorescence potentiometric dyes, the electrical properties of the
      transverse tubular system in amphibian skeletal muscle fibers. In this paper we
      expand on recent observations using the fluorescent potentiometric indicator di-8
      ANEPPS to investigate structural and functional properties of the transverse
      tubular system in mammalian skeletal muscle fibers. Two-photon laser scanning
      confocal fluorescence images of live muscle fibers suggest that the distance
      between consecutive rows of transverse tubules flanking the Z-lines remains
      relatively constant in muscle fibers stretched to attain sarcomere lengths of up
      to 3.5 microm. Furthermore, the combined use of two-microelectrode
      electrophysiological techniques with microscopic fluorescence spectroscopy and
      imaging allowed us to compare the spectral properties of di-8-ANEPPS fluorescence
      in fibers at rest, with those of fluorescence transients recorded in stimulated
      fibers. We found that although the indicator has excitation and emission peaks at
      470 and 588 nm, respectively, fluorescence transients display optimal fractional
      changes (13%/100 mV) when using filters to select excitation wavelengths in the
      530-550 nm band and emissions beyond 590 nm. Under these conditions, results from
      tetanically stimulated fibers and from voltage-clamp experiments suggest strongly
      that, although the kinetics of di-8-ANEPPS transients in mammalian fibers are
      very rapid and approximate those of the surface membrane electrical recordings,
      they arise from the transverse tubular system membranes.

PMID- 16645745
TI  - Comparison of responses to electrical stimulation and whisker deflection using
      two different voltage-sensitive dyes in mouse barrel cortex in vivo.
AB  - We examined the spatial structure of noise in optical recordings made with two
      commonly used voltage-sensitive dyes (RH795 and RH1691) in mouse barrel cortex in
      vivo, and determined that the signal-to-noise ratio of the two dyes was
      comparable when averaging over barrel-sized areas, or at single pixels distant
      from large blood vessels. We examined the spatiotemporal development of whisker-
      and electrically-evoked optical responses by quantifying the area of activated
      cortical surface as a function of time. Whisker and electrical stimuli activated
      cortical areas between 0.2-2.0 mm(2) depending on intensity. More importantly,
      both types of activation recruited cortical area at similar rates and showed a
      linear relationship between the maximal activated area and the peak rate of
      increase of the activated area. We propose a general rule of supragranular
      cortical activation in which the initial spreading speed of the response
      determines the total activated area, independent of the type of activation.
      Finally, despite comparable single-response kinetics, we observed greater paired
      pulse depression of whisker-evoked responses relative to electrically-evoked
      responses.

PMID- 16645746
TI  - Primary vagal projection to the contralateral non-NTS region in the embryonic
      chick brainstem revealed by optical recording.
AB  - Using multiple-site optical recording with the voltage-sensitive dye, NK2761, we
      found that vagus nerve stimulation in the embryonic chick brainstem elicits
      postsynaptic responses in an undefined region on the contralateral side. The
      characteristics of the contralateral optical signals suggested that they
      correspond to the monosynaptic response that is related to the vagal afferent
      fibers. The location of the contralateral response was different from the vagal
      motor nucleus (the dorsal motor nucleus of the vagus nerve) and sensory nucleus
      (the nucleus of the tractus solitarius), and other brainstem nuclei that receive
      primary vagal projection. These results show that the vagus nerve innervates and
      makes functional synaptic connections in a previously unreported region of the
      brainstem, and suggest that sensory information processing mediated by the vagus
      nerve is more complex than expected.

PMID- 16645744
TI  - Initiation of sodium spikelets in basal dendrites of neocortical pyramidal
      neurons.
AB  - Cortical information processing relies critically on the processing of electrical
      signals in pyramidal neurons. Electrical transients mainly arise when excitatory
      synaptic inputs impinge upon distal dendritic regions. To study the dendritic
      aspect of synaptic integration one must record electrical signals in distal
      dendrites. Since thin dendritic branches, such as oblique and basal dendrites, do
      not support routine glass electrode measurements, we turned our effort towards
      voltage-sensitive dye recordings. Using the optical imaging approach we found and
      reported previously that basal dendrites of neocortical pyramidal neurons show an
      elaborate repertoire of electrical signals, including backpropagating action
      potentials and glutamate-evoked plateau potentials. Here we report a novel form
      of electrical signal, qualitatively and quantitatively different from
      backpropagating action potentials and dendritic plateau potentials. Strong
      glutamatergic stimulation of an individual basal dendrite is capable of
      triggering a fast spike, which precedes the dendritic plateau potential. The
      amplitude of the fast initial spikelet was actually smaller that the amplitude of
      the backpropagating action potential in the same dendritic segment. Therefore,
      the fast initial spike was dubbed "spikelet". Both the basal spikelet and plateau
      potential propagate decrementally towards the cell body, where they are reflected
      in the somatic whole-cell recordings. The low incidence of basal spikelets in the
      somatic intracellular recordings and the impact of basal spikelets on soma-axon
      action potential initiation are discussed.

PMID- 16645754
TI  - Joint application of independent component analysis and non-stationary
      fluctuation analysis for studying the mechanisms of the early phase of long-term
      potentiation in the rat hippocampus.
AB  - Interest in studies of synaptic plasticity have led to the development of
      specific methods for analyzing evoked postsynaptic currents: quantum analysis,
      component analysis, non-stationary fluctuation analysis, etc. However, the use
      and interpretation of these methods are not always consistent, which leads to the
      acquisition of contradictory results from similar experiments. In the present
      study, simulations were used to analyze the influences of the heterogeneity of
      the shapes of postsynaptic currents on the results obtained by non-stationary
      fluctuation analysis. Assessment of postsynaptic channel conductivity was found
      to depend on the number of synapses involved in generating the response. It is
      hypothesized that the increase in the assessment of AMPA channel conductivity
      reported in the literature in conditions of long-term potentiation may be related
      to changes in the synaptic composition of postsynaptic currents. The hypothesis
      was tested using a new method for independent component analysis. Studies using
      the simulation showed that the joint application of this method and non
      stationary fluctuation analysis avoids errors of this type. The procedures
      developed here were applied to data obtained from physiological experiments; the
      results of this exercise provided general support for the hypothesis.

PMID- 16645755
TI  - Limited plasticity of difference neurons in the visual cortex and hippocampus in
      rabbits during the oddball (random substitutions) test.
AB  - The activity of 41 visual cortex neurons and 20 hippocampal field CA1 neurons was
      studied in rabbits during application of the oddball stimulation paradigm using
      color stimuli of different intensities. Among these cells, about one third were
      plastic cells (34% of cortical cells and 37% of hippocampal cells). These neurons
      showed significant increases in late responses, at times 200-500 and 200-1000
      msec for visual cortex neurons and 300-550 msec for hippocampal neurons, to rare
      deviant stimuli of lesser intensity as compared with responses to the frequent
      standard stimuli of greater intensity. The initial peak of the response (40-120
      msec), the "difference discharge," remained stable in responses to deviant and
      standard stimuli throughout the experiment. It is suggested that the
      strengthening of the late components of neuron responses to rare deviant stimuli
      (limited plasticity) reflects inclusion of the mechanisms of the orientational
      reflex.

PMID- 16645756
TI  - Effects of partial intraspecies deprivation of rats on short-term image memory.
AB  - An individual's zoosocial experience plays a significant role in the formation of
      adaptive behavior in animals. Published data show that significant restriction of
      intraspecies interactions induces impairments of higher nervous activity,
      including such functions as learning, memory, and the control of emotions. These
      changes are particularly marked when deprivation of zoosocial interactions occurs
      in the early stage of the animal's postnatal development. We have previously
      demonstrated that psychogenic stress in rats reared from an early age (from 14
      days after birth) in conditions of visual and tactile deprivation leads to
      impairment of long-term (conditioned reflex) memory functions, this being
      accompanied by significant suppression of self-regulatory brain activity. The aim
      of the present work was to investigate the effects of partial intraspecies
      deprivation in early ontogenesis on overall behavior and short-term memory in
      adult rats.

PMID- 16645757
TI  - Sensory innervation of the brain (primary interoceptor neurons of the brain and
      their asynaptic dendrites).
AB  - Published data and our own studies on the sensory innervation of the brain are
      summarized. Primary interoceptive sensory neurons were analyzed: brain neurons
      bearing cilia; supraependymal plexuses and intraependymal neurons in contact with
      the cerebrospinal fluid; Cajal-Retzius neurons in the boundary layer of the
      cerebral cortex; Dolgo-Saburov paravasal neurons in the brain and spinal cord;
      Lugaro cells in the cerebellum; and various synaptically NO-positive neurons in
      the cerebral cortex, whose asynaptic dendrites innervate the precapillary space.
      Consideration of the lack of pain sensitivity of the brain and the parenchymatous
      tissues of the internal organs, which contain local primary sensory neurons
      similar to intramural metasympathetic sensory neurons of Dogel type II, led to
      the hypothesis that brain and other intraorgan tissue receptors are involved in
      short "autonomic" reflex arcs controlling only local metabolism but not pain
      reactions.

PMID- 16645758
TI  - Plasticity of secretory neurons in the supraoptic and paraventricular nuclei of
      the hypothalamus on exposure to light.
AB  - Light and electron microscopic methods were used to analyze changes in secretory
      neurons in the supraoptic (SON) and paraventricular (PVN) nuclei in the
      hypothalamus in 100 adult male rats at time points from the first minutes to 180
      days after 48 hours of full-time exposure to bright light. At the early time
      points after exposure, the cellular formulae of the SON and PVN shifted towards
      functionally active neurons with minimal quantities of secretory granules, large
      nuclei and nucleoli, low RNA contents, small numbers of rough endoplasmic
      reticulum cisterns, vacuoles, and lysosomes in the perikarya. The number of cells
      depositing secretion was greater than in controls at 24 h in the SON and PVN and
      at 10 days in the SON. Normalization of the cellular formula and the structural
      organization of the protein-synthesizing apparatus of PVN neurons occurred at 10
      30 days, with normalization in the SON at 30-180 days. These data provide
      evidence that the range of plasticity of neurons in the PVN on exposure to full
      time bright light was more significant than that in the SON.

PMID- 16645759
TI  - Spatial organization and morphometric characteristics of histaminergic neurons in
      the rat brain.
AB  - We report here a study addressing the spatial organization, densities, numbers,
      sizes, and shapes of histaminergic neurons in the rat hypothalamus. Studies were
      performed on 50 rats using histochemical and morphometric methods, computer image
      analysis, and three-dimensional reconstruction of the histaminergic nuclei of the
      hypothalamus. The results demonstrated that the total bilateral volume of the
      histaminergic nuclei of the rat brain amounts to 0.5 mm(3): the E2 nucleus
      occupies 40% of the total volume, E4 occupies 35%, E3 occupies 13%, E5 occupies
      9%, and E1 occupies 3%. The distribution density of monoamine oxidase B neurons
      in the histaminergic nuclei of the rat hypothalamus decreased in the order E1 >
      E3 > E2 (the "compact" nuclei) > E4 (an "intermediate" density nucleus) > E5 (the
      "diffuse part"). The mean number of histaminergic neurons in the rat hypothalamus
      was 37200 +/- 2800; the E2 nucleus contained 54% of these cells, E3 contained
      23%, E4 contained 6%, E1 contained 7%, and E5 contained 0.32%. The E1-E3 nuclei
      were dominated by small and intermediate-sized neurons, round in shape, and the
      E5 nucleus was dominated by intermediate and large neurons, fusiform in shape. A
      subpopulation of giant histaminergic neurons was detected in the E4-E5 nuclei.

PMID- 16645760
TI  - Formation of the structural and ultrastructural organization of the striatum in
      early postnatal ontogenesis of rats in altered conditions of embryonic
      development.
AB  - Light (Nissl and Golgi methods) and electron microscopy methods were used to
      study the formation of the structure of the striatum during the first two weeks
      after birth in rats subjected to acute hypoxia at different times of
      embryogenesis. The dynamics of the physiological development of the same
      population of rats were studied in parallel. Hypoxia at day 13.5 of embryogenesis
      was found to lead to delayed neurogenesis (delayed establishment of elements of
      the neuropil and differentiation of cells) and abnormalities in the structure of
      the striatum (degeneration, particularly chromatolysis, of neurons and the
      appearance of glial nodes). Morphometric analysis demonstrated a decrease in the
      total number of cells in the striatum; small changes in large neurons were seen.
      Hypoxia at day 18.5 of embryogenesis produced no significant changes. Structural
      abnormalities were accompanied by changes in the process of the animals'
      physiological development. The data obtained here show that changes in the
      conditions of embryogenesis (hypoxia) during the period of the most intense
      proliferation of neuroblasts in the forebrain lead to impairment of the process
      of formation of striatal nervous tissue and the body as a whole in the period of
      early postnatal ontogenesis.

PMID- 16645761
TI  - The weight and linear dimensions of the human cerebellum.
AB  - Data on the weights and linear dimensions of the cerebella from the corpses of 80
      women and 140 men aged 20-90 years were studied, using standard methods for
      statistical data analysis. A relationship was found between differences in the
      weight and the linear dimensions of the cerebellum and differences in skull size.
      Cerebellar weight and transverse dimensions were greater in males than in
      females. There were decreases in the weight and linear dimensions of the
      cerebellum after age 60 years.

PMID- 16645762
TI  - Regeneration of the rat spinal cord after thoracic segmentectomy: restoration of
      the anatomical integrity of the spinal cord.
AB  - Segmentectomy of the spinal cord (SC) was performed in 28 rats at the level of
      the tenth thoracic vertebra. Scar formation at the operation site was studied,
      along with the completeness of the anatomical integrity of the SC, in control
      animals (group 1) and after filling of the defect with the neural matrix
      Spherogel (group 2) and with Spherogel containing embryonic nerve cells (group
      3). The defect in the SC in animals of the control group was filled with fibrin
      masses by 1-2 weeks, while connective tissues scars were already formed by this
      time in rats of experimental groups 2 and 3. By 10-11 weeks, these animals showed
      partial recovery of movement in the three lower limb joints. The scar tissue and
      adjacent zones of the SC showed large quantities of regenerating fine myelinated
      nerve fibers. These were clearly evident in the zones of the cranial and caudal
      margins, to the extent of the appearance of typical SC tissue. In preparations
      obtained from control animals, fine myelinated fibers were noted in the immediate
      vicinity of SC substance, while nerve fibers were few in number in scar tissue
      and the cellular bands of the transitional zone.

PMID- 16645763
TI  - Morphofunctional characteristics of neurons in the spinal ganglia of the dog in
      the post-distraction period.
AB  - The aims of the present work were to study the morphofunctional state of neurons
      in the spinal ganglia and to perform a comparative analysis of changes in neuron
      glial relationships after lengthening of the hindlimb of mongrel dogs by 14-16%
      of initial at different rates. Longitudinal serial sections of thickness 5 microm
      of the L6, L7, and S1 ganglia (n = 36) stained with thionine and cresyl violet by
      the Nissl method and hallocyanine and chromic alum by the Einarson method were
      examined. Reversible transformations of the structure of some neurons were seen
      at 45-48 days, these consisting of hyperchromia of the cytoplasm and nucleus,
      peripheral chromatolysis, displacement of the nucleolus, and increases in the
      quantities of perineuronal and interneuronal gliocytes. Changes were most marked
      in the ganglia on the side of limb lengthening at a rate of 3 mm/day, while the
      smallest changes were seen on the side contralateral to limb lengthening at a
      rate of 1 mm/day.

PMID- 16645764
TI  - Eye-rotation-induced spatial reorganization of horizontal connections in field 17
      of the cat cortex.
AB  - Six cats with rotation of one or both eyes (strabismus) produced surgically in
      the early postnatal period demonstrated torsional deviation of the eyes by 10-20
      degrees in addition to the rotation. The spatial distribution of retrograde
      labeled neurons in field 17 was studied by microiontophoretic administration of
      horseradish peroxidase into individual cortical columns in fields 17 and 18.
      These studies showed that rotation of the eyes increased the extent of horizontal
      neuronal connections in field 17 along the projection of the vertical meridian of
      the field of vision. It is suggested that this reorganization of neuronal
      connections may support functional changes compensating for eye rotation, as
      described in the literature.

PMID- 16645765
TI  - Neural stem cells and their role in recovery processes in the nervous system.
AB  - Published data and our own results on the identification, cultivation, and
      potential therapeutic utilization of regional stem cells from humans and animals
      are reviewed. Pluripotent stem cells have been shown to proliferate in the
      subventricular zone of the lateral ventricles and the subgranular zone of the
      dentate gyrus of the hippocampal formation in adult human and animal brains. Data
      on the hierarchical organization of genetic networks in controlling individual
      development suggest a possible functional role for repeat mini-and microsatellite
      DNA sequences in stem cell differentiation. Methods of using human bone marrow as
      a source of stem cells for restoring damaged tissue in the brain are discussed.
      Heat-shock proteins have been found to block the formation of glial scars after
      neural transplantation. The viability of stem cells after transplantation can be
      increased by transfer of genes for neurotrophic growth factors into the genomes
      of the neurons undergoing transplantation.

PMID- 16645766
TI  - Formation of the neocortex in mice developing in conditions of prenatal serotonin
      deficiency.
AB  - We report here detailed studies of structural changes occurring in the mouse
      neocortex formed and stratified in conditions of prenatal experimental blockade
      of serotonin synthesis. Studies were performed using F1(C57BL/CBA) hybrid mice.
      Endogenous serotonin levels were decreased by exposure of the mice to
      parachlorophenylalanine, which inhibits the key serotonin synthesis enzyme
      tryptophan hydroxylase. Offspring brains were studied at 1, 5 and 10 days (n = 10
      15 for each time point) of postnatal development. Controls consisted of intact
      animals at the same periods of development. These experiments showed that
      prenatal blockade of serotonin synthesis leads to impaired formation of all
      neocortical layers, impaired growth, development, and differentiation of neurons,
      and alterations in neuron shape and size. As postnatal development proceeded,
      significant numbers of neurons died in the brain structures of these animals.

PMID- 16645767
TI  - Neuronal organization of the reticular nucleus of the thalamus in adult humans.
AB  - The neuronal composition of the thalamic reticular nucleus was studied in serial
      sections of the sagittal and frontal projections impregnated with silver nitrate
      by the Golgi method. The neuronal composition of the reticular nucleus of the
      human thalamus was wider than has previously been described in animals and
      humans. This nucleus, apart from two types of large, sparsely branched, long
      dendrite, reticular, aspiny, neurons, i.e., types R1 and R2, contained cells with
      spines. Intermediate and small, sparsely-branched, short-dendrite neurons and
      densely-branched cells with spines were demonstrated. The principles of the
      organization of the reticular nucleus of the human thalamus are described.

PMID- 16645768
TI  - Apoptosis of hypothalamic neurosecretory cells in stress mice at different stages
      of ontogenesis.
AB  - The aim of the present work was to identify the role of cycloferon in the
      apoptosis of cells in the neurosecretory centers of the hypothalamus in young and
      old mice in conditions of immobilization stress. Apoptotic cells were identified
      by staining with ethidium bromide. The optical density of the detection product
      of the antiapoptotic protein Bcl-2 was also studied in cells of the supraoptic
      and paraventricular (PVN) nuclei. Cycloferon was found to decrease the level of
      apoptosis in the neurosecretory centers of the hypothalamus via a Bcl-2
      independent pathway. Administration of cycloferon before stress had no effect on
      the number of apoptotic cells, except in the PVN of old mice, where apoptosis was
      inhibited.

PMID- 16645769
TI  - Distribution of DNA, proteins, and lipids in cells of the olfactory bulb in rats
      of different ages.
AB  - Luminescence and absorption stains specific for DNA (acridine orange, ethidium
      bromide), proteins (silver nitrate), and lipids (Sudan III) were used to study
      the distribution of DNA, proteins, and lipids in sections of the olfactory bulb
      in rats, studies being performed after fixation of brains with paraformaldehyde.
      DNA was found to be more abundant in the glomerular cell layer than the mitral
      cell layer. Higher quantities of DNA were present in the granular layer, located
      beneath the mitral layer. The characteristics of cell layers in the olfactory
      bulb were studied in rats aged two days and one month. There were differences
      between the layers of rats of different ages in terms of the content and
      distribution of DNA, though there were no differences in the total protein or
      lipid contents. Glomeruli were immature in two-day-old rats.

PMID- 16645770
TI  - Modification of histogenetic processes in rat nervous tissue after administration
      of dexamethasone during prenatal development.
AB  - Experiments on rats using confocal microscopy and immunocytochemistry showed that
      single doses of the synthetic corticosteroid hormone dexamethasone to pregnant
      females during the period of elevated sensitivity of the developing fetal nervous
      system (day 13 of intrauterine development) led to modification of histogenetic
      processes in the brain, reflected as changes in its structural-functional
      characteristics during postnatal ontogenesis.

PMID- 16645771
TI  - Primary sensory neurons in the central nervous system.
AB  - Published data and our own results relating to exteroceptor and a variety of
      interceptor neurons in the brain and spinal cord, such as intraspinal Hesse
      ocelli and light-sensitive epiphyseal and ependymal neurons, are presented. Light
      sensitive ganglion neurons in invertebrates are also described, along with
      intrinsic spinal cord bipolar sensory neurons within the spinal cord, primary
      chemo-and thermosensitive neurons, and sensory unipolar neurons associated with
      the three fine "central nerves" of Motavkin, which perforate the sheath of the
      spinal cord and ending with bush-like receptors close to vessels or near the
      ependyma of the central canal. Data on all known intracortical interoceptors in
      vertebrates are generalized into a single scheme. It is hypothesized that the
      brains of animals and humans have an intrinsic sensory innervation comparable
      with the innervation of other organs and containing local primary sensory neurons
      and their asynaptic dendrites, which can be divided into two groups: interceptor
      and exteroceptor.

PMID- 16645772
TI  - Sensory innervation of the brain - myth or reality?
AB  - This article provides a critical analysis of the concepts of the sensory
      innervation of the brain and spinal cord presented in Sotnikov's articles in
      issues 2 and 3 of this volume. Criteria for the identification of intracerebral
      primary sensory neurons and the possible roles of neuronal cilia are discussed.
      The significance of asynaptic dendrites and bipolar cells is considered. The
      importance of the correct use of a variety of terms is emphasized, and the need
      for using combined morphological and electrophysiological analysis in
      investigating sensory intracerebral exteroceptors is noted.

PMID- 16645773
TI  - Comparative analysis of the baseline spike activity of neurons in the fastigial
      nucleus of the cerebellum at different durations of exposure to vibration.
AB  - Acute experiments on Nembutal-anesthetized (40 mg/kg, i.p.) white rats with
      extracellular recording and analysis of baseline spine activity of neurons in the
      fastigial nucleus of the cerebellum were performed in normal conditions and after
      exposure to vibration for 5, 10, and 15 days. The distribution of neurons in
      terms of the regularity and dynamics of spike flows and the modality of
      interspike interval histograms were determined, along with the mean neuron spike
      frequency and the coefficient of variation of interspike intervals. The results
      showed that the most significant changes in neuron activity in fastigial nucleus
      cells were formed during the first ten days of vibration. On day 15, there was a
      tendency for measures to return to control levels.

PMID- 16645774
TI  - Adrenocortical and thyroid systems of rats during the initial period of
      nociceptive influences.
AB  - Two phases were identified in the initial period of formation of the
      adrenocortical reaction to acute nociception. The first phase (at 10-15 sec)
      consisted of an "urgent" mobilization of the " basal" reserves of hormonally
      active substances and was characterized by suppression of corticoliberin activity
      in the hypothalamus and extrahypothalamic brain structures in rats, with a
      parallel increase in the plasma concentration of adrenocorticotropic hormone,
      draining of corticosteroid reserves in the adrenals, and decreases in blood
      corticosterone levels on the background of increases in corticosterone levels in
      target organs. The second phase, the hypercompensation phase, involved
      progressive increases in the titers of study substances. Significant changes in
      adrenal and blood aldosterone levels were seen only 2.5 min after nociception.
      Rearrangements of thyroid status were also biphasic. However, unlike the primary
      adrenocortical response, the first phase of the stress-related thyroid response
      involved a marked increase in plasma thyroxine and triiodothyronine, while the
      second involved a selective decrease in the thyroxine concentration to normal
      levels.

PMID- 16645775
TI  - Effects of an NO synthase inhibitor on aggressive and sexual behavior in male
      crickets.
AB  - The mechanisms of the effects of some types of behavior on others have received
      little study. The present investigation addresses the phenomenon present in male
      crickets of the species Gryllus bimaculatus, consisting of the powerful
      activation by transient flight (3 min) of aggression to another male and of the
      female courtship program. We found that flight did not evoke these behavioral
      changes in males injected with the NO synthase inhibitor LNNA. The intensity and
      duration of fights with another male, the frequency of ritual singing by the
      victor, and the intensity with which the victor pursued the vanquished only
      increased significantly after flight in control male crickets injected with
      Ringer's solution, but not in experimental crickets. Similarly, flown males
      injected with LNNA were no different from unflown males in terms of the intensity
      of female courtship (the latent period and relative duration of courtship
      singing); in controls, the latent period was significantly shorter and the
      duration of singing was significantly greater in flown crickets. LNNA had no
      effect on aggressive or sexual behavior in unflown males. These results
      demonstrate that flight may increase NO synthesis, making a significant
      contribution to the formation of the flight-evoked behavioral state.

PMID- 16645776
TI  - The dynamism of cutaneous lupus erythematosus: mild discoid lupus erythematosus
      evolving into SLE with SCLE and treatment-resistant lupus panniculitis.
AB  - We present a 47-year-old Caucasian female who initially presented with mild
      discoid lupus erythematosus that evolved into systemic lupus erythematosus with
      subacute cutaneous LE and treatment-recalcitrant lupus panniculitis. Conventional
      therapy with antimalarials, systemic steroids, azathioprine, cyclophosphamide,
      methotrexate, and pulse doses of methylprednisolone did not control the course of
      the disease. Cyclosporin-A treatment led to clinical improvement and maintained
      remission.

PMID- 16645777
TI  - IOF World Congress on Osteoporosis, 2-6 June 2006, Toronto, Canada. Abstracts.

PMID- 16645781
TI  - RIKEN structural genomics beamlines at the SPring-8; high throughput protein
      crystallography with automated beamline operation.
AB  - RIKEN Structural Genomics Beamlines, BL26B1 & BL26B2 at the SPring-8, have been
      constructed for the structural genomics research. The main feature of the
      beamline is full automation of the successive data collections to maximize the
      beam-time efficiency. The beamline optics adopted a standard design commonly used
      for the SPring-8 bending magnet beamlines. Beamline instruments are operated by
      centralized control system through the computer network to achieve the automatic
      operation. The core part of the beamline development is a sample management
      system composed of sample changer robots for laboratory and beamline, and a
      networked sample database. BL26B1 has started user operation, and the automatic
      operation with the sample management system has been implemented at BL26B2.

PMID- 16645783
TI  - Motor functions but not learning and memory are impaired upon repeated exposure
      to sub-lethal doses of methyl parathion.
AB  - Our previous work showed that repeated exposure to methyl parathion (MP) caused a
      prolonged inhibition of acetylcholinesterase (AChE) activity (approximately 80%)
      and down-regulation of M(1) and M(2) muscarinic receptors (up to 38%) in rats at
      brain regions, including frontal cortex, striatum, hippocampus and thalamus. In
      the present neurobehavioral study, we found this repeated MP treatment had
      suppressant effects on rat's locomotor activity. However, we observed no evidence
      of long-term effects of MP on associative learning and memory. Our data
      demonstrated that repeated exposure to MP caused some functional deficits in CNS,
      but motor activity and associative learning/memory process might differ in the
      sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be
      mediated via reciprocal balance between cholinergic and dopaminergic systems at
      striatum following cholinergic over-stimulation. Our findings also suggest that
      the CNS deficits induced by repeated exposure to MP or other organophosphate (OP)
      pesticides cannot be attributed entirely to the inhibition of AChE. To accurately
      assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP,
      novel biomarkers besides in vivo anticholinesterase potency are needed.

PMID- 16645784
TI  - Outpatient use of systemic antibiotics in Croatia.
AB  - According to the results of the European Surveillance of Antimicrobial
      Consumption (ESAC), outpatient antibiotic use in Croatia in 2001 (17.6 DDD per
      1000 inhabitants per day) was comparable to the median use of 24 European
      countries, which were able to deliver valid data.

PMID- 16645787
TI  - CT appearance of isolated dextroversion.
AB  - We present the multidetector CT appearance of a case of isolated dextroversion.
      Dextroversion is a rare anomaly characterized by extreme right-sided rotation of
      the heart resulting in dextrocardia with the left ventricle anterior and to the
      left of the right ventricle. The diagnosis is easily made with ECG-gated
      multidetector CT.

PMID- 16645788
TI  - Eight-row multidetector computed tomography coronary angiography evaluation of
      significant coronary artery disease in patients with severe aortic valve
      stenosis.
AB  - BACKGROUND: The aim of this study was to evaluate whether 8-row multidetector
      computed tomography coronary angiography (MDCT-CA) could replace invasive
      conventional coronary angiography (CCA) in patients with acquired severe aortic
      valve stenosis (AS). Coronary artery disease (CAD) diagnosis should be obtained
      with a noninvasive method in patients with AS undergoing valvular replacement. We
      evaluated the diagnostic accuracy of MDCT-CA in detecting high-grade (> or =50%)
      stenoses in the main coronary arteries in patients with AS. METHODS: Twenty-three
      patients with acquired severe AS underwent both CCA and MDCT-CA. We calculated
      the total and volumetric calcium scores and evaluated the image quality of each
      coronary segment as assessable or nonassessable for stenosis. The images of the
      arteries were evaluated for the occurrence of artifacts and the presence of high
      grade stenoses (> or =50%) by visual estimation and comparison with that of CCA.
      RESULTS: Of the 322 segments screened 224 were assessable for stenosis. Heavy
      calcium load rendered 37 (38%) of the 98 coronary segments nonassessable.
      Compared to CCA, MDCT-CA had a sensitivity of 63%, a specificity of 96%, a
      positive predictive value of 52%, and a negative predictive value of 98% for > or
      =50% stenoses in the main coronary arteries. CONCLUSIONS: Eight-row MDCT-CA
      revealed a low sensitivity in detecting significant coronary artery disease in
      patients with acquired severe AS. High calcium burden decreased visualization of
      the lumen and complicated most often a correct assessment. In this patient group,
      CCA should still remain the primary pre-surgical test to rule out coronary
      lesions requiring revascularization.

PMID- 16645789
TI  - Potential interest of intra-aorta ultrasound imaging for the diagnosis of aortic
      penetrating atherosclerotic ulcer.
AB  - A 72-year-old man was admitted to our hospital for acute back pain.
      Transesophageal echocardiography (TEE), computed tomography (CT) and magnetic
      resonance imaging (MRI) all showed the presence of intramural hematoma (IMH)
      located in the descending aorta, with bilateral pleural effusions. The patient
      was initially referred for medical therapy and 'watchful waiting'. However, he
      continued to have back pain, so we decided to perform invasive aortography
      examination and intra-aortic ultrasound (IAU) imaging. No penetrating aortic
      ulcer (PAU) was found on multiple angiographic views, but intra-aorta ultrasound
      imaging clearly showed a PAU measuring 3x1 mm(2) in connection with the
      intramural hematoma. Even retrospective analysis of CT images failed to reveal
      this PAU. Therefore, we think that IAU imaging may be a useful tool in the
      diagnosis of PAU.

PMID- 16645791
TI  - Discovering new classes of Brugia malayi asparaginyl-tRNA synthetase inhibitors
      and relating specificity to conformational change.
AB  - SLIDE software, which models the flexibility of protein and ligand side chains
      while docking, was used to screen several large databases to identify inhibitors
      of Brugia malayi asparaginyl-tRNA synthetase (AsnRS), a target for anti-parasitic
      drug design. Seven classes of compounds identified by SLIDE were confirmed as
      micromolar inhibitors of the enzyme. Analogs of one of these classes of
      inhibitors, the long side-chain variolins, cannot bind to the adenosyl pocket of
      the closed conformation of AsnRS due to steric clashes, though the short side
      chain variolins identified by SLIDE apparently bind isosterically with adenosine.
      We hypothesized that an open conformation of the motif 2 loop also permits the
      long side-chain variolins to bind in the adenosine pocket and that their
      selectivity for Brugia relative to human AsnRS can be explained by differences in
      the sequence and conformation of this loop. Loop flexibility sampling using
      Rigidity Optimized Conformational Kinetics (ROCK) confirms this possibility,
      while scoring of the relative affinities of the different ligands by SLIDE
      correlates well with the compounds' ranks in inhibition assays. Combining ROCK
      and SLIDE provides a promising approach for exploiting conformational flexibility
      in structure-based screening and design of species selective inhibitors.

PMID- 16645793
TI  - Genetic tools, Kuhnean theoretical shift and the geneticization process.
AB  - The growing use of genetic tests in medical practice has a strong influence on
      some widespread notions of health and unhealth. Two consequences of this
      phenomenon are: (i) important changes in the meaning of these current notions
      and, therefore, (ii) the arrival of a new taxonomy or rearrangement for the so
      called "health-concepts". This paper attempts to demonstrate that both facts fuel
      a theoretical change that might be considered a model of scientific Kuhnean
      change in a fundamental aspect. On the other hand, this theoretical shift process
      offers the basis for approaching a present-day controversy, i.e. whether Western
      society is going through a period of geneticization or not, from a new
      perspective.

PMID- 16645794
TI  - Motivating donors to genetic research? Anthropological reasons to rethink the
      role of informed consent.
AB  - In this article we explore the contribution from social anthropology to the
      medical ethical debates about the use of informed consent in research, based on
      blood samples and other forms of tissue. The article springs from a project
      exploring donors' motivation for providing blood and healthcare data for genetic
      research to be executed by a Swedish start-up genomics company. This article is
      not confined to empirical findings, however, as we suggest that anthropology
      provides reason to reassess the theoretical understanding of autonomy as
      generally defined by Beauchamp and Childress. Careful consideration of the trust
      expressed by donors through the act of donation, furthermore, suggests that there
      is reason to redirect the ethical scrutiny from informed consent to issues
      concerning institutional arrangements and social responsibility. In particular,
      we suggest that an anthropological approach could facilitate a reconsideration of
      the political implications of using informed consent as a regulatory practice in
      tissue-based research.

PMID- 16645795
TI  - Deafness, genetics and dysgenics.
AB  - It has been argued by some authors that our reaction to deaf parents who choose
      deafness for their children ought to be compassion, not condemnation. Although I
      agree with the reasoning proposed I suggest that this practice could be regarded
      as unethical. In this article, I shall use the term "dysgenic" as a culturally
      imposed genetic selection not to achieve any improvement of the human person but
      to select genetic traits that are commonly accepted as a disabling condition by
      the majority of the social matrix; in short as a handicap. As in eugenics,
      dysgenics can be achieved in a positive and a negative way. Positive dysgenics
      intends to increase the overall number of people with a particular genetic trait.
      Marriage between deaf people or conceiving deaf children through reproductive
      technology are examples of positive dysgenics. Negative dysgenics can be obtained
      through careful prenatal or pre-implantation selection and abortion (or
      discarding) of normal embryos and foetuses. Only deaf children would be allowed
      to live. If dysgenics is seen as a programmed genetic intervention that
      undesirably shapes the human condition--like deliberately creating deaf or dwarf
      people--the professionals involved in reproductive technologies should answer the
      question if this should be an accepted ethical practice because the basic human
      right to an open future is violated.

PMID- 16645796
TI  - 'Medicine's next goldmine?' The implications of new genetic health technologies
      for the health service.
AB  - There is considerable uncertainty about the implications of the new genetics for
      health services. These are the enthusiasts who argue that molecular genetics will
      transform health care and others argue that the scope for genetic interventions
      is limited. The aim of this paper is to examine some of the questions, tensions
      and difficulties which face health care providers particularly in developed
      countries as they try to come to terms with the dilemmas raised by new genetic
      health care technologies (NGHTs). It identifies questions for research which may
      help the development of robust and flexible strategies for implementation.

PMID- 16645797
TI  - Genetic testing and private insurance--a case of "selling one's body"?
AB  - Arguments against the possible use of genetic test results in private health and
      life insurance predominantly refer to the problem of certain gene carriers
      failing to obtain affordable insurance cover. However, some moral intuitions
      speaking against this practice seem to be more fundamental than mere concerns
      about adverse distributional effects. In their perspective, the central ethical
      problem is not that some people might fail to get insurance cover because of
      their 'bad genes', but rather that some people would manage to get insurance
      cover because of their 'good genes'. This paper tries to highlight the ethical
      background of these intuitions. Their guiding idea appears to be that, by
      pointing to his favourable test results, a customer might make an attempt to
      'sell his body'. The rationale of this concept is developed and its applicability
      to the case at issue is critically investigated. The aim is to clarify an
      essential objection against the use of genetic information in private insurance
      which has not yet been openly addressed in the academic debate of the topic.

PMID- 16645798
TI  - Catharsis and moral therapy I: a Platonic account.
AB  - This paper aims at analysing the ancient Greek notions of catharsis (clearing up,
      cleaning), to holon (the whole) and therapeia (therapy, treatment, healing) to
      assess whether they may be of help in addressing a set of questions concerning
      the didactics of medical ethics: What do medical students actually experience and
      learn when they attend classes of medical ethics? How should teachers of medical
      ethics proceed didactically to make students benefit morally from their teaching?
      And finally, to what extent and in what forms and formats can the kind of
      cathartic treatment envisaged by Plato still be considered a necessary
      preliminary to moral learning? The three questions will be addressed by means of
      a reconstructive analysis and assessment of the Platonic notions of catharsis and
      holistic therapy present in the Charmides and the Sophist. Besides, the didactic
      potential of Plato's dialogue form and moral regimen will be tried out. The
      ultimate aim is to investigate the possibilities of developing a therapeutic
      conception of medical ethics.

PMID- 16645799
TI  - An argument for the use of Aristotelian method in bioethics.
AB  - The main claim of this paper is that the method outlined and used in Aristotle's
      Ethics is an appropriate and credible one to use in bioethics. Here "appropriate"
      means that the method is capable of establishing claims and developing concepts
      in bioethics and "credible" that the method has some plausibility, it is not open
      to obvious and immediate objection. It begins by suggesting why this claim
      matters and then gives a brief outline of Aristotle's method. The main argument
      is made in three stages. First, it is argued that Aristotelian method is credible
      because it compares favourably with alternatives. In this section it is shown
      that Aristotelian method is not vulnerable to criticisms that are made both of
      methods that give a primary place to moral theory (such as utilitarianism) and
      those that eschew moral theory (such as casuistry and social science approaches).
      As such, it compares favourably with these other approaches that are vulnerable
      to at least some of these criticisms. Second, the appropriateness of Aristotelian
      method is indicated through outlining how it would deal with a particular case.
      Finally, it is argued that the success of Aristotle's philosophy is suggestive of
      both the credibility and appropriateness of his method.

PMID- 16645800
TI  - Human tissue samples and ethics--attitudes of the general public in Sweden to
      biobank research.
AB  - PURPOSE: To survey the attitudes of the general public in Sweden to biobank
      research and to discuss the findings in the light of some well-known ethical
      principles. METHODS: A questionnaire was used to survey the opinions of the
      general public in Sweden, and an ethical analysis (using the principles of
      autonomy, non-maleficence, beneficence and justice) was performed to discuss the
      possible conditions of such research. FINDINGS: Between 3 and 9% answered that
      they did not want their samples to be collected and stored in a biobank. Many
      respondents required information about the purpose of the research and wanted to
      be able to consent or refuse. About one third of the respondents said they would
      have answered differently if financial gain was involved and those who commented
      indicated a more negative attitude. The principle of autonomy maintains that the
      right to self-determination should be respected, and the principles of non
      maleficence and beneficence that the probable harms and benefits resulting from a
      particular project by using samples from a biobank should be balanced. The
      general public disagree about how these principles are to be balanced.
      INTERPRETATION: In the light of the findings different interpretations of the
      situation as well as possible alternatives are discussed in this paper.

PMID- 16645801
TI  - Life extension research: an analysis of contemporary biological theories and
      ethical issues.
AB  - Many opinions and ideas about aging exist. Biological theories have taken hold of
      the popular and scientific imagination as potential answers to a "cure" for
      aging. However, it is not clear what exactly is being cured or whether aging
      could be classified as a disease. Some scientists are convinced that aging will
      be biologically alterable and that the human lifespan will be vastly extendable.
      Other investigators believe that aging is an elusive target that may only be
      "statistically" manipulatable through a better understanding of the operational
      principles of systems situated within complex environments. Not only is there
      confusion over definitions but also as to the safety of any potential
      intervention. Curing cell death, for example, may lead to cell cancer. The search
      for a cure for aging is not a clearly beneficial endeavour. This paper will
      first, describe contemporary ideas about aging processes and second, describe
      several current life extension technologies. Third, it analyses these theories
      and technologies, focusing on two representative and differing scientific points
      of view. The paper also considers the public health dilemma that arises from life
      extension research and examines two issues, risk/benefit ratio and informed
      consent, that are key to developing ethical guidelines for life extension
      technologies.

PMID- 16645802
TI  - Organizing the public health-clinical health interface: theoretical bases.
AB  - This article addresses the issue of the interface between public health and
      clinical health within the context of the search for networking approaches geared
      to a more integrated delivery of health services. The articulation of an
      operative interface is complicated by the fact that the definition of networking
      modalities involves complex intra- and interdisciplinary and intra- and
      interorganizational systems across which a new transversal dynamics of
      intervention practices and exchanges between service structures must be
      established. A better understanding of the situation is reached by shedding light
      on the rationale underlying the organizational methods that form the bases of the
      interface between these two sectors of activity. The Quebec experience
      demonstrates that neither the structural-functionalist approach, which emphasizes
      remodelling establishment structures and functions as determinants of
      integration, nor the structural-constructivist approach, which prioritizes
      distinct fields of practice in public health and clinical health, adequately
      serves the purpose of networking and integration. Consequently, a theoretical
      reframing is imperative. In this regard, structuration theory, which fosters the
      simultaneous study of methods of inter-structure coordination and inter-actor
      cooperation, paves the way for a better understanding of the situation and, in
      turn, to the emergence of new integration possibilities.

PMID- 16645803
TI  - Psychiatry under pressure: reflections on psychiatry's drift towards a
      reductionist biomedical conception of mental illness.
AB  - We argue that contemporary psychiatry adopts a defensive strategy vis-a-vis
      various external sources of pressure. We will identify two of these sources--the
      plea for individual autonomy and the idea of Managed Care--and explain how they
      have promoted a strict biomedical conception of disease. The demand for
      objectivity, however, does not take into account the complexity of mental
      illness. It ignores that the psychiatrist's profession is essentially
      characterized by fragility: fluctuating between scientific reduction and the
      irreducible complexity of reality. Therefore, the psychiatrist is not in need of
      hard and fast rules, but of judgment. At the end, we suggest that philosophy
      could inject some healthy uncertainty within psychiatry in order to restore its
      fragile identity. Our examples are drawn from the Dutch situation but we are
      confident that they apply to other countries as well.

PMID- 16645804
TI  - Autonomy, wellbeing, and the case of the refusing patient.
AB  - A moral problem arises when a patient refuses a treatment that would save her
      life. Should the patient be treated against her will? According to an influential
      approach to questions of biomedical ethics, certain considerations pertaining to
      individual autonomy provide a solution to this problem. According to this
      approach, we should respect the patient's autonomy and, since she has made an
      autonomous decision against accepting the treatment, she should not be treated.
      This article argues against the view that our answer to the question of whether
      or not the refusing patient ought to be treated should be based on these kinds of
      considerations pertaining to individual autonomy and maintains that finding a
      plausible answer to this question presupposes that we resolve questions
      concerning subjectivity and objectivity of individual wellbeing.

PMID- 16645811
TI  - Accuracy of optimized chemical-exchange parameters derived by fitting CPMG R2
      dispersion profiles when R2(0a) not = R2(0b).
AB  - The transverse relaxation rate, R2, measured as a function of the effective field
      (R2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well
      suited to detect conformational exchange in proteins. The dispersion data are
      commonly fitted by a two-site (sites a and b) exchange model with four
      parameters: the relative population, pa, the difference in chemical shifts of the
      two sites, deltaomega, the correlation time for exchange, tau(ex), and the
      intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of
      chemical exchange), R2(0). Although the intrinsic relaxation rates of the two
      sites, R2(0a) and R2(0b), can differ, they are normally assumed to be the same
      (i.e., R2(0a) = R2(0b) = R2(0)) when fitting dispersion data. The purpose of this
      investigation is to determine the magnitudes of the errors in the optimized
      exchange parameters that are introduced by the assumption that R2(0a) = R2(0b).
      In order to accomplish this goal, we first generated synthetic constant-time CPMG
      R2 dispersion data assuming two-site exchange with R2(0a) not equal R2(0b), and
      then fitted the synthetic data assuming two-site exchange with R2(0) = R2(0a) =
      R2(0b). Although all the synthetic data generated assuming R2(0a) not equal
      R2(0b) were well fitted (assuming R2(0a) = R2(0b)), the optimized values of pa
      and tau(ex) differed from their true values, whereas the optimized values of
      deltaomega values did not. A theoretical analysis using the Carver-Richards
      equation explains these results, and yields simple, general equations for
      estimating the magnitudes of the errors in the optimized parameters, as a
      function of (R2(0a) - R2(0b)).

PMID- 16645812
TI  - Structural studies of Bcl-xL/ligand complexes using 19F NMR.
AB  - Fluorine atoms are often incorporated into drug molecules as part of the lead
      optimization process in order to improve affinity or modify undesirable metabolic
      and pharmacokinetic profiles. From an NMR perspective, the abundance of
      fluorinated drug leads provides an exploitable niche for structural studies using
      19F NMR in the drug discovery process. As 19F has no interfering background
      signal from biological sources, 19F NMR studies of fluorinated drugs bound to
      their protein receptors can yield easily interpretable and unambiguous structural
      constraints. 19F can also be selectively incorporated into proteins to obtain
      additional constraints for structural studies. Despite these advantages, 19F NMR
      has rarely been exploited for structural studies due to its broad lines in
      macromolecules and their ligand complexes, leading to weak signals in 1H/19F
      heteronuclear NOE experiments. Here we demonstrate several different experimental
      strategies that use 19F NMR to obtain ligand-protein structural constraints for
      ligands bound to the anti-apoptotic protein Bcl-xL, a drug target for anti-cancer
      therapy. These examples indicate the applicability of these methods to typical
      structural problems encountered in the drug development process.

PMID- 16645813
TI  - Computational and empirical trans-hydrogen bond deuterium isotope shifts suggest
      that N1-N3 A:U hydrogen bonds of RNA are shorter than those of A:T hydrogen bonds
      of DNA.
AB  - Density functional theory calculations of isolated Watson-Crick A:U and A:T base
      pairs predict that adenine 13C2 trans-hydrogen bond deuterium isotope shifts due
      to isotopic substitution at the pyrimidine H3, (2h)Delta13C2, are sensitive to
      the hydrogen-bond distance between the N1 of adenine and the N3 of uracil or
      thymine, which supports the notion that (2h)Delta13C2 is sensitive to hydrogen
      bond strength. Calculated (2h)Delta13C2 values at a given N1-N3 distance are the
      same for isolated A:U and A:T base pairs. Replacing uridine residues in RNA with
      5-methyl uridine and substituting deoxythymidines in DNA with deoxyuridines do
      not statistically shift empirical (2h)Delta13C2 values. Thus, we show
      experimentally and computationally that the C7 methyl group of thymine has no
      measurable affect on (2h)Delta13C2 values. Furthermore, (2h)Delta13C2 values of
      modified and unmodified RNA are more negative than those of modified and
      unmodified DNA, which supports our hypothesis that RNA hydrogen bonds are
      stronger than those of DNA. It is also shown here that (2h)Delta13C2 is context
      dependent and that this dependence is similar for RNA and DNA.

PMID- 16645814
TI  - Combining NMR relaxation with chemical shift perturbation data to drive protein
      protein docking.
AB  - The modeling of biomolecular complexes by computational docking using the known
      structures of their constituents is developing rapidly to become a powerful tool
      in structural biology. It is especially useful in combination with even limited
      experimental information describing the interface. Here we demonstrate for the
      first time the use of diffusion anisotropy in combination with chemical shift
      perturbation data to drive protein-protein docking. For validation purposes we
      make use of simulated diffusion anisotropy data. Inclusion of this information,
      which can be derived from NMR relaxation rates and reports on the orientation of
      the components of a complex with respect to the rotational diffusion tensor,
      substantially improves the docking results.

PMID- 16645815
TI  - Band-selective 13C homonuclear 3D spectroscopy for solid proteins at high field
      with rotor-synchronized soft pulses.
AB  - We demonstrate improved 3D 13C-13C-13C chemical shift correlation experiments for
      solid proteins, utilizing band-selective coherence transfer, scalar decoupling
      and homonuclear zero-quantum polarization transfer. Judicious use of selective
      pulses and a z-filter period suppress artifacts with a two-step phase cycle,
      allowing higher digital resolution in a fixed measurement time. The novel
      correlation of C(ali)-C(ali)-CX (C(ali) for aliphatic carbons, CX for any carbon)
      reduces measurement time by an order of magnitude without sacrificing digital
      resolution. The experiment retains intensity from side-chain carbon resonances
      whose chemical shift dispersion is critical to minimize spectral degeneracy for
      large proteins with a predominance of secondary structure, such as beta-sheet
      rich fibrillar proteins and alpha-helical membrane proteins. We demonstrate the
      experiment for the beta1 immunoglobulin binding domain of protein G (GB1) and
      fibrils of the A30P mutant of alpha-synuclein, which is implicated in Parkinson's
      disease. Selective pulses of duration comparable the rotor period give optimal
      performance, but must be synchronized with the spinning in non-trivial ways to
      minimize chemical shift anisotropy recoupling effects. Soft pulses with a small
      bandwidth-duration product are best for exciting the approximately 70 ppm
      bandwidth required for aliphatic-only dimensions.

PMID- 16645816
TI  - Identification of zinc-ligated cysteine residues based on 13Calpha and 13Cbeta
      chemical shift data.
AB  - Although a significant number of proteins include bound metals as part of their
      structure, the identification of amino acid residues coordinated to non
      paramagnetic metals by NMR remains a challenge. Metal ligands can stabilize the
      native structure and/or play critical catalytic roles in the underlying
      biochemistry. An atom's chemical shift is exquisitely sensitive to its electronic
      environment. Chemical shift data can provide valuable insights into structural
      features, including metal ligation. In this study, we demonstrate that overlapped
      13Cbeta chemical shift distributions of Zn-ligated and non-metal-ligated cysteine
      residues are largely resolved by the inclusion of the corresponding 13Calpha
      chemical shift information, together with secondary structural information. We
      demonstrate this with a bivariate distribution plot, and statistically with a
      multivariate analysis of variance (MANOVA) and hierarchical logistic regression
      analysis. Using 287 13Calpha/13Cbeta shift pairs from 79 proteins with known
      three-dimensional structures, including 86 13Calpha and 13Cbeta shifts for 43 Zn
      ligated cysteine residues, along with corresponding oxidation state and secondary
      structure information, we have built a logistic regression model that
      distinguishes between oxidized cystines, reduced (non-metal ligated) cysteines,
      and Zn-ligated cysteines. Classifying cysteines/cystines with a statistical model
      incorporating all three phenomena resulted in a predictor of Zn ligation with a
      recall, precision and F-measure of 83.7%, and an accuracy of 95.1%. This model
      was applied in the analysis of Bacillus subtilis IscU, a protein involved in iron
      sulfur cluster assembly. The model predicts that all three cysteines of IscU are
      metal ligands. We confirmed these results by (i) examining the effect of metal
      chelation on the NMR spectrum of IscU, and (ii) inductively coupled plasma mass
      spectrometry analysis. To gain further insight into the frequency of occurrence
      of non-cysteine Zn ligands, we analyzed the Protein Data Bank and found that 78%
      of the Zn ligands are histidine and cysteine (with nearly identical frequencies),
      and 18% are acidic residues aspartate and glutamate.

PMID- 16645820
TI  - Laser flash photolysis study on antioxidant properties of hydroxycinnamic acid
      derivatives.
AB  - The antioxidant properties of hydroxycinnamic acid derivatives (HCA) were studied
      by laser flash photolysis. The transient species with maximum absorption at 360
      nm were assigned to the phenoxyl radical of HCA. The SO (4) (.-) induced
      oxidation of HCA was also investigated. It was shown that the interaction of SO
      (4) (.-) with HCA resulted in the formation of HCA phenoxyl radicals with rate
      constants of 2.0-3.9 x 10(9 )M(-1) s(-1). The reactions of HCA with triplet state
      of benzophenone were analyzed and quenching rate constants of 4.3-7.8 x 10(9 )M(
      1) s(-1) were determined.

PMID- 16645821
TI  - Cloning, purification, and characterization of chitosanase from Bacillus sp.
      DAU101.
AB  - A chitosanase-producing Bacillus sp. DAU101 was isolated from Korean traditional
      food. This strain was identified on the basis of phylogenetic analysis of the 16S
      rDNA sequence, gyrA gene, and phenotypic analysis. The gene encoding chitosanase
      (csn) was cloned and sequenced. The csn gene consisted of an open reading frame
      of 837 nucleotides and encodes 279 amino acids with a deduced molecular weight of
      31,420 Da. The deduced amino acid sequence of the chitosanase from Bacillus sp.
      DAU101 exhibits 88 and 30 % similarity to those from Bacillus subtilis and
      Pseudomonas sp., respectively. The chitosanase was purified by glutathione S
      transferase fusion purification system. The molecular weight of purified enzyme
      was about 27 kDa, which suggests the deletion of a signal peptide by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The pH and temperature optima
      of the enzyme were 7.5 and 50 degrees C, respectively. The enzyme activity was
      increased by about 1.6-fold by the addition of 5 or 10 mM Ca(2+). However, Hg(2+)
      and Ni(+) ions strongly inhibited the enzyme. The enzyme produced, GlcN(2-4),
      were the major products from a soluble chitosan.

PMID- 16645822
TI  - Growth of Escherichia coli MG1655 on LB medium: determining metabolic strategy
      with transcriptional microarrays.
AB  - Expression profiles of genes related to stress responses, substrate assimilation,
      acetate metabolism, and biosynthesis were obtained by monitoring growth of
      Escherichia coli MG1655 in Luria-Bertani (LB) medium with transcriptional
      microarrays. Superimposing gene expression profiles on a plot of specific growth
      rate demonstrates that the cells pass through four distinct physiological states
      during fermentation before entering stationary phase. Each of these states can be
      characterized by specific patterns of substrate utilization and cellular
      biosynthesis corresponding to the nutrient status of the medium. These data allow
      the growth phases of the classical microbial growth curve to be redefined in
      terms of the physiological states and environmental changes commonly occurring
      during bacterial growth in batch culture on LB medium.

PMID- 16645823
TI  - [Unusual orbital trauma with diplopia].

PMID- 16645836
TI  - Atypical abdominal paediatric lymphangiomatosis: diagnosis aided by diffusion
      weighted MRI.
AB  - We report a 4-year-old child with a mesenteric mass, which on ultrasound, CT and
      conventional MRI appeared solid, raising lymphoma as a possible diagnosis.
      Diffusion weighted MRI (DW-MRI), however, suggested a low-cellularity lesion,
      making lymphoma less likely. Biopsy confirmed lymphangioma. DW-MRI may be a
      useful adjunct to conventional imaging, even in the abdomen.

PMID- 16645839
TI  - [(111)In]DOTATOC as a dosimetric substitute for kidney dosimetry during
      [(90)Y]DOTATOC therapy: results and evaluation of a combined gamma camera/probe
      approach.
AB  - PURPOSE: During [(90)Y]DOTATOC therapy, for determination of kidney doses a
      conventional approach using co-injected [(111)In]DOTATOC was evaluated for
      validity, reliability and reproducibility as well as for the influence of
      methodological variations and bremsstrahlung. Biologically effective doses were
      estimated by calculating the relative effectiveness (RE) of kidney doses.
      METHODS: Fractionated [(90)Y]DOTATOC therapy (n=20 patients, 3.1+/-0.7
      GBq/therapy cycle, 45 therapy cycles) included co-injection of 157+/-37 MBq
      [(111)In]DOTATOC and a nephroprotective infusion regimen. From serial gamma
      camera/probe measurements, individual region of interest (ROI) sets were
      established and kidney doses were determined according to MIRDOSE3 (corrected for
      individual kidney mass) by use of three methodological variants: (1) correction
      for interfering organs (liver/spleen) and background activity, (2) correction for
      interfering organs alone and (3) no corrections. A phantom study was performed
      with (111) In alone and with (111)In +(90)Y to estimate the influence of (90)Y
      bremsstrahlung. RESULTS: Mean kidney dose (method 1, n=20 patients, 20 therapy
      cycles) was 1.51+/-0.60 Gy/GBq [(90)Y]DOTATOC (1.41+/-0.48 Gy/GBq for n=20
      patients, 45 therapy cycles). With partial correction (method 2) or no correction
      (method 3) for interfering activity, kidney doses increased significantly, to
      2.71+/-1.26 Gy/GBq and 3.15+/-1.22 Gy/GBq, respectively. The span of REs ranged
      from 1.02 to 1.24. Inter-observer variability was as high as +/-32% (+/-2SD).
      (90)Y bremsstrahlung accounted for a 4-11% underestimation of obtained target
      activity. CONCLUSION: The obtained kidney doses are highly influenced by
      methodological variations. Full correction for interfering activity clearly
      underestimates kidney doses. By comparison, (90)Y bremsstrahlung and variability
      in the relative effectiveness of kidney doses cause minor bias. Inter-observer
      variability must be considered when interpreting kidney doses.

PMID- 16645840
TI  - Evaluation of (123)I-orthoiodohippurate single kidney clearance rate by renal
      sequential scintigraphy in a large cohort of likely normal subjects aged between
      0 and 18 years.
AB  - PURPOSE: Age-related values of (123)I-orthoiodohippurate (OIH) single kidney
      clearance rate (Cl) were estimated in a large cohort of likely normal children
      aged between 0 and 18 years. METHODS: Among 4,111 children examined in the past
      10 years, 917 were selected with the following inclusion criteria: (a) mild
      ultrasonographic hydronephrosis with right differential renal function (DRF) <53%
      and >47% (498 pts), (b) known or suspected urinary tract infection with normal
      ultrasound, serum creatinine and DMSA and DRF <53% and >47% (419 pts). (123)I-OIH
      Cl was assessed using a validated gamma camera method. Children were divided into
      21 age classes: from 0 to 2 years, eight 3-month classes; from 2 to 14 years,
      twelve 1-year classes; from 14 to 18 years, one 4-year class. RESULTS: Cl,
      plotted against age, was fitted using an increasing function (y=a-be-cx). Mean
      (123)I-OIH-Cl of 1,834 kidneys was 306+/-22 ml/min/1.73 m(2) BSA. Mean (123)I-OIH
      Cl of the right and left kidneys was 307+/-23 and 305+/-22 ml/min/1.73 m(2) BSA,
      respectively (p<0.002). The best-fitting (123)I-OIH-Cl growing function was:
      Cl=311-230e-0.69xAge (months). (123)I-OIH-Cl improved progressively starting from
      birth, reaching 96% and 98% of the mature value at 1 and 1.5 years, respectively.
      (123)I-OIH-Cl at birth (age=0) was 81 ml/min/1.73 m(2) BSA. After 18.6 days of
      life, the renal function had doubled its starting value, and it reached a plateau
      of 311 ml/min/1.73 m(2) BSA at 2 years. CONCLUSION: This work represents a
      systematic evaluation of ERPF by a gamma camera method in a large cohort of
      selected likely normal paediatric subjects.

PMID- 16645841
TI  - ATM/ATR-related checkpoint signals mediate arsenite-induced G2/M arrest in
      primary aortic endothelial cells.
AB  - Epidemiological studies have demonstrated a high association of inorganic arsenic
      exposure with vascular disease. Our recent in vitro studies have linked this
      vascular damage to vascular endothelial dysfunction induced by arsenic exposure.
      However, cell-cycle arrest induced by arsenic and its involvement in vascular
      dysfunction remain to be clarified. In this study, we employed primary porcine
      aortic endothelial cells to investigate regulatory mechanisms of G2/M phase
      arrest induced by arsenite. Our study revealed that lower concentrations of
      arsenite (1 and 3 microM) increased cell proliferation, whereas higher
      concentrations of arsenite (10, 20, and 30 microM) inhibited cell proliferation
      together with correlated increases in G2/M phase arrest. We found that this
      arsenite-induced G2/M phase arrest was accompanied by accumulation and/or
      phosphorylation of checkpoint-related molecules, including p53, Cdc25B, Cdc25C,
      and securin. Inhibition of activations of these checkpoint-related molecules by
      caffeine significantly attenuated the 30-microM arsenite-induced G2/M phase
      arrest by 93%. Our data suggest that the DNA damage responsive kinases ATM
      (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) play critical
      roles in arsenite-induced G2/M phase arrest in aortic endothelial cells possibly
      via regulation of checkpoint-related signaling molecules including p53, Cdc25B,
      Cdc25C, and securin.

PMID- 16645842
TI  - Cadmium restores in vitro splicing activity inhibited by zinc-depletion.
AB  - Zinc (Zn)-depletion inhibits the second step of RNA splicing, namely exon
      ligation. To investigate the effects of cadmium (Cd) and other metal ions on RNA
      splicing inhibited by Zn-depletion, we measured in vitro splicing activities in
      the presence of these metals. Zn-depletion in the splicing reaction mixture was
      achieved by addition of a Zn-chelator, 1,10-phenanthroline. Cd(II) at 1, 5 and 10
      microM restored the splicing activity to 2, 24 and 72% of that in the control
      reaction mixture, while higher concentrations of Cd(II) decreased the splicing
      activity, and more than 50 microM Cd(II) showed a complete absence of spliced
      products. Hg(II) also restored the splicing activity, albeit to a lesser extent,
      since 5 and 10 microM Hg(II) restored the splicing activity to 3 and 4% of the
      control value. The other metal ions examined in this study, Co(II), Cu(II),
      Mg(II) and Mn(II), did not show any restoration of the splicing activity. We
      concluded that Cd(II) could restore the in vitro splicing activity inhibited by
      Zn-depletion, although higher concentrations of Cd(II) prevented progress of the
      RNA splicing reaction. These results suggest that Cd(II) has a bifunctional
      property regarding RNA splicing, and is stimulatory at low concentrations and
      inhibitory at high concentrations.

PMID- 16645843
TI  - White matter abnormalities in the anterior temporal lobe suggest the side of the
      seizure foci in temporal lobe epilepsy.
AB  - INTRODUCTION: White matter abnormalities in the anterior temporal lobe (WAATL)
      are sometimes observed on magnetic resonance (MR) images of patients with
      temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could
      indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in
      TLE patients. METHODS: We reviewed 112 consecutive patients with medically
      intractable TLE. We compared the side of seizure foci on EEG (preoperative and
      intraoperative) and MR images. RESULTS: Both loss of gray-white matter
      demarcation and increased signal intensity changes in the anterior white matter
      (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were
      present on the same side as the seizure foci on preoperative intracranial EEG
      with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG)
      in all the patients. In 47 patients, MR images showed WAATL and focal lesions
      that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure
      foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45
      patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion
      were on the same side. In three patients, no focal lesions were seen but WAATL
      were present on the same side as the seizure foci on sEEG and ECG. In four
      patients, MR images showed focal lesions for which epileptogenicity was
      questionable, and WAATL on the same side as the seizure foci on EEG. CONCLUSION:
      WAATL are clinically useful because they indicate the side of the seizure foci.

PMID- 16645846
TI  - Kolmogorov's differential equations and positive semigroups on first moment
      sequence spaces.
AB  - Spatially implicit metapopulation models with discrete patch-size structure and
      host-macroparasite models which distinguish hosts by their parasite loads lead to
      infinite systems of ordinary differential equations. In several papers, a this
      related theory will be developed in sufficient generality to cover these
      applications. In this paper the linear foundations are laid. They are of own
      interest as they apply to continuous-time population growth processes (Markov
      chains). Conditions are derived that the solutions of an infinite linear system
      of differential equations, known as Kolmogorov's differential equations, induce a
      C0-semigroup on an appropriate sequence space allowing for first moments. We
      derive estimates for the growth bound and the essential growth bound and study
      the asymptotic behavior. Our results will be illustrated for birth and death
      processes with immigration and catastrophes.

PMID- 16645851
TI  - Mitochondrial D-loop (CA)n repeat length heteroplasmy: frequency in a German
      population sample and inheritance studies in two pedigrees.
AB  - Sequence analysis of the human mitochondrial genome (mtDNA) has proven to be a
      valuable tool in forensic identity testing and the analysis of crime scene
      stains. In contrast to the very expensive sequencing technique, typing of
      different length variants can greatly facilitate screening of a large number of
      traces for their relevance during casework. Within the mitochondrial control
      region, a dinucleotide (CA)( n ) repeat locus is present. To assess the
      discrimination power of this marker, we have determined (CA)( n ) allele
      distribution and the frequency of heteroplasmy in a population sample of 2,458
      Germans. The inclination to develop heteroplasmic mixtures (CA)( n )/(CA)( n-1)
      was positively correlated with the number of CA repeats in the mtDNA. In
      addition, we have studied the inheritance patterns of (CA)( n ) repeat sequence
      heteroplasmy in two pedigrees. In one pedigree, we also found a length
      heteroplasmy in the homopolymeric C-tract (nt 303-309). Our data show stable
      inheritance of heteroplasmy within the homopolymeric C-stretch, but rather
      unstable inheritance regarding the (CA)( n ) repeat locus.

PMID- 16645849
TI  - P2 receptors and neuronal injury.
AB  - Extracellular adenosine 5'-triphosphate (ATP) was proposed to be an activity
      dependent signaling molecule that regulates glia-glia and glia-neuron
      communications. ATP is a neurotransmitter of its own right and, in addition, a
      cotransmitter of other classical transmitters such as glutamate or GABA. The
      effects of ATP are mediated by two receptor families belonging either to the P2X
      (ligand-gated cationic channels) or P2Y (G protein-coupled receptors) types. P2X
      receptors are responsible for rapid synaptic responses, whereas P2Y receptors
      mediate slow synaptic responses and other types of purinergic signaling involved
      in neuronal damage/regeneration. ATP may act at pre- and postsynaptic sites and
      therefore, it may participate in the phenomena of long-term potentiation and long
      term depression of excitatory synaptic transmission. The release of ATP into the
      extracellular space, e.g., by exocytosis, membrane transporters, and connexin
      hemichannels, is a widespread physiological process. However, ATP may also leave
      cells through their plasma membrane damaged by inflammation, ischemia, and
      mechanical injury. Functional responses to the activation of multiple P2
      receptors were found in neurons and glial cells under normal and
      pathophysiological conditions. P2 receptor-activation could either be a cause or
      a consequence of neuronal cell death/glial activation and may be related to
      detrimental and/or beneficial effects. The present review aims at demonstrating
      that purinergic mechanisms correlate with the etiopathology of brain insults,
      especially because of the massive extracellular release of ATP, adenosine, and
      other neurotransmitters after brain injury. We will focus in this review on the
      most important P2 receptor-mediated neurodegenerative and neuroprotective
      processes and their beneficial modulation by possible therapeutic manipulations.

PMID- 16645853
TI  - A systematic analysis of disease-associated variants in the 3' regulatory regions
      of human protein-coding genes I: general principles and overview.
AB  - The 3' regulatory regions (3' RRs) of human genes play an important role in
      regulating mRNA 3' end formation, stability/degradation, nuclear export,
      subcellular localization and translation and are consequently rich in regulatory
      elements. Although 3' RRs contain only approximately 0.2% of known disease
      associated mutations, this is likely to represent a rather conservative estimate
      of their actual prevalence. In an attempt to catalogue 3' RR-mediated disease and
      also to gain a greater understanding of the functional role of regulatory
      elements within 3' RRs, we have performed a systematic analysis of disease
      associated 3' RR variants; 121 3' RR variants in 94 human genes were collated.
      These included 17 mutations in the upstream core polyadenylation signal sequence
      (UCPAS), 81 in the upstream sequence (USS) between the translational termination
      codon and the UCPAS, 6 in the left arm of the 'spacer' sequence (LAS) between the
      UCPAS and the pre-mRNA cleavage site (CS), 3 in the right arm of the 'spacer'
      sequence (RAS) or downstream core polyadenylation signal sequence (DCPAS) and 7
      in the downstream sequence (DSS) of the 3'-flanking region, with 7 further
      mutations being treated as isolated examples. All the UCPAS mutations and the
      rather unusual cases of the DMPK, SCA8, FCMD and GLA mutations exert a
      significant effect on the mRNA phenotype and are usually associated with
      monogenic disease. By contrast, most of the remaining variants are polymorphisms
      that exert a comparatively minor influence on mRNA expression, but which may
      nevertheless predispose to or otherwise modify complex clinical phenotypes.
      Considerable efforts have been made to validate/elucidate the mechanisms through
      which the 3' untranslated region (3' UTR) variants affect gene expression. It is
      hoped that the integrative approach employed here in the study of naturally
      occurring variants of actual or potential pathological significance will serve to
      complement ongoing efforts to identify all functional regulatory elements in the
      human genome.

PMID- 16645854
TI  - ["Fast-track surgery": Perioperative management].
AB  - The multimodal therapeutic concept of fast-track surgery is directed against the
      pathophysiologic functional changes following elective surgery. This concept has
      been proven to reduce postoperative morbidity and convalescence. This benefit is
      based on an interdisciplinary approach by surgeons, anaesthesiologists, nurses,
      and physiotherapy staff to optimise perioperative care in order to decrease
      surgically-induced stress. Fast-track surgery after elective colorectal surgery
      has been shown to reduce the rate of postoperative complications and shorten
      hospital stay significantly. A prerequisite for successfully implementing this
      concept is the willingness of the participating surgeons to abandon conventional
      traditions. In addition to abdominal procedures, the basic concept of fast-track
      surgery has been successfully instituted in other surgical fields, such as
      urology.

PMID- 16645855
TI  - Demographic effects of extreme winter weather in the barn owl.
AB  - Extreme weather events can lead to immediate catastrophic mortality. Due to their
      rare occurrence, however, the long-term impacts of such events for ecological
      processes are unclear. We examined the effect of extreme winters on barn owl
      (Tyto alba) survival and reproduction in Switzerland over a 68-year period
      (approximately 20 generations). This long-term data set allowed us to compare
      events that occurred only once in several decades to more frequent events. Winter
      harshness explained 17 and 49% of the variance in juvenile and adult survival,
      respectively, and the two harshest winters were associated with major population
      crashes caused by simultaneous low juvenile and adult survival. These two winters
      increased the correlation between juvenile and adult survival from 0.63 to 0.69.
      Overall, survival decreased non-linearly with increasing winter harshness in
      adults, and linearly in juveniles. In contrast, brood size was not related to the
      harshness of the preceding winter. Our results thus reveal complex interactions
      between climate and demography. The relationship between weather and survival
      observed during regular years is likely to underestimate the importance of
      climate variation for population dynamics.

PMID- 16645860
TI  - Preservation of caprine preantral follicle viability after cryopreservation in
      sucrose and ethylene glycol.
AB  - Caprine preantral follicles within ovarian fragments were cryopreserved in the
      absence or presence of 0.5 M sucrose with or without 1 M dimethyl sulfoxide
      and/or 1 M ethylene glycol (EG). After being thawed, they were washed in minimum
      essential medium with or without 0.3 M sucrose. Histological analysis of follicle
      integrity immediately after cryopreservation showed consistent beneficial effects
      of including sucrose in the three cryoprotectant solutions analyzed when tissue
      was thawed without sucrose (53.9+/-14.8-82.4+/-3.2% normal vs 27.6+/-1.6-36.6+/
      6.5%, P<0.05). However, in further studies, the addition of sucrose to the thaw
      solutions proved detrimental or of no benefit. An analysis of the cryopreserved
      material with calcein-AM and ethidium homodimer (markers for living and dead
      cells, respectively) gave comparable results to those obtained by histology.
      Follicles cryopreserved in EG, EG plus sucrose, or sucrose alone were cultured in
      vitro for 24 h following warming. During this culture period, viability fell most
      rapidly in material cryopreserved in sucrose alone and was no longer correlated
      with either the viability or integrity estimates made immediately after warming.
      By contrast, the viability of follicles cryopreserved in EG with sucrose and then
      cultured for 24 h was not significantly different from the cultured non-frozen
      controls. These results indicate that cryopreservation in 1 M EG plus 0.5 M
      sucrose combined with thawing without sucrose is effective for caprine ovarian
      tissue.

PMID- 16645861
TI  - Compound subretinal prostheses with extra-ocular parts designed for human trials:
      successful long-term implantation in pigs.
AB  - BACKGROUND: Subretinal implants aim to replace photoreceptor function in patients
      suffering from degenerative retinal disease like retinitis pigmentosa by
      topically applying electrical stimuli in the subretinal space. This study-as a
      last step before upcoming human trials-explored a newly developed surgical
      technique for permanent implantation of complex subretinal implants with extra
      ocular parts. METHODS: The implant consisted of a microphoto-diode array (MPDA)
      with 1550 electrodes and a 4x4 array of gold electrodes for direct electrical
      stimulation; both were mounted onto a polyimide foil for transscleral placement
      into the subretinal space. The foil carried connection lanes to a silicone cable
      that was implanted under the skin and led to a stimulator box in the animal's
      neck. Surgery was performed in 11 domestic pigs. Improved vitreo-retinal surgical
      technique consisted of a 180 degrees peripheral retinotomy and use of diathermy
      to penetrate the choroid in order to avoid choroidal haemorrhage. Subretinal
      forceps were used to place the implant safely onto the retinal pigment epithelium
      before the retina was flattened, peripheral laser photocoagulation was applied
      and the eye was filled with silicon oil. The implant was stabilized by a scleral
      fixation patch, use of a metal clamp with bone screws on the animal's skull and a
      tissue ring under the animal's skin in the neck. Behaviour was observed in the
      freely moving animals after direct subretinal electrical stimulation and
      funduscopy, optical coherence tomography, fluorescein angiography and histology
      were performed. RESULTS: All implants were successfully placed subretinally. In
      three animals a proliferative vitreo-retinopathy was observed after approximately
      2 weeks. Otherwise, funduscopy and OCT demonstrated complete retinal attachment
      and FA showed no retinal vascular abnormalities over and around the implant. The
      animals showed clear behavioural reactions to electrical stimulation over the
      whole examination period. Histological examination failed to show any voltage
      induced alteration in the cellular architecture of the retina overlying the
      stimulation electrodes. CONCLUSIONS: This study demonstrates the feasibility of a
      new surgical procedure for highly safe and controlled implantation of complex
      subretinal devices with extra-ocular parts. The new implant design proved to be
      safely implantable in free-moving pigs for an observation period of 4 weeks.

PMID- 16645863
TI  - Clinicopathological characteristics, microsatellite instability, and expression
      of mucin core proteins and p53 in colorectal mucinous adenocarcinomas in relation
      to location.
AB  - It has been suggested that right-sided and left-sided colorectal cancer may arise
      by different mechanisms. However, there have been few studies of mucinous
      adenocarcinoma (MA) in relation to location. Therefore, we analyzed
      clinicopathological characteristics, microsatellite instability (MSI), and
      expression of MUC1, MUC2, MUC5AC mucin core proteins, and p53 by
      immunohistochemistry in relation to tumor location. Ninety-six consecutive
      colorectal MAs and ninety-eight nonmucinous adenocarcinomas (nMAs) were
      investigated. Right-sided MAs, by comparison with those on the left side, were
      characterized by older age, larger tumor size, lower stage at presentation,
      peritumoral lymphocytic response, background of serrated adenoma, MSI-H
      phenotype, higher MUC2 and MUC5AC expression, and lower p53 protein
      overexpression. Right-sided nMAs, relative to those on the left side, were
      associated with MSI-H phenotype, higher MUC2 and MUC5AC expression, and lower p53
      protein overexpression. Thus, MSI-H phenotype, expression of MUC2 and MUC5AC, and
      infrequent p53 protein overexpression are associated with right-sided location as
      well as mucinous histology. In univariate analysis, right-sided location had a
      favorable effect on disease specific survival of the patients with MA, although
      it is not an independent predictor of survival. Our results indicate that MA is a
      distinctive form of colorectal cancer and has different phenotypes depending on
      tumor location.

PMID- 16645865
TI  - [It is never too late--nutrition in the elderly].
AB  - Increasing life expectancy is associated with the hope for independent and
      healthy living in old age. Autonomy and quality of life until old age are goals
      of health policy. A good nutritional status is an essential premise for that.
      Although the aetiology of many chronic diseases has not been studied to the last
      detail yet, one can state that a diet covering needs and age-appropriate physical
      activity increasingly help people to experience old age in a physically and
      mentally good constitution. In the "middle-aged" and young seniors,
      overweight/obesity and related conditions dominate. In old and oldest seniors,
      malnutrition poses a problem caused by unnoticed deficits in nutrient and fluid
      intake. They are often connected with conditions like dementia and should not be
      underestimated. The dietary situation of seniors living independently is normally
      better than that of seniors in nursing homes. Since the therapy of malnutrition
      in old age is very difficult and cumbersome, prevention plays a crucial role.
      Against this background, particular effort is required especially in senior
      housing facilities to ensure a diet covering needs, which preserves the pleasure
      of eating and drinking.

PMID- 16645866
TI  - [Outpatient and inpatient medical care of the elderly].
AB  - This contribution discusses the outpatient and inpatient medical care of elderly
      patients in Germany. The paper first focuses on the increasing utilization of the
      two care sectors especially by the very old in the sense of a "geriatrization" of
      the system followed by a detailed analysis of the costs associated with a higher
      frequency of contact with the medical care system. On the one hand, the
      determining factor for outpatient treatment costs is more likely to be the
      patient's age rather than the type of disease. On the other hand it was found
      that inpatient treatment costs are associated more with closeness to death than
      with patient's age. A third central point beside these quantitative aspects
      continues to be the discussion about current deficits in the care of elderly
      patients. While the discussion on the outpatient medical care centers on
      physician-related factors and their influence on the quality of care exemplified
      by depression and dementia, the discussion on inpatient care focuses on
      structural problems. This is followed by the discussion of central organizational
      and research needs in the medical care of the elderly.

PMID- 16645867
TI  - [Aging and sexuality].
AB  - This contribution describes sexual desire, activity and satisfaction of people
      aged 45-91 years on the basis of an empirical study conducted in the German
      speaking part of Switzerland. Sexual desire and activity diminish with age but
      there is a great variability. Sexual satisfaction remains stable in elderly
      people. Physical, hormonal and neuronal changes cause a greater vulnerability for
      sexual problems but relationship, psychosocial and biographical factors as well
      as coping strategies have a strong moderating effect. The medicalization of the
      sexuality of aging people is critically depicted. Recommendations for health care
      practitioners are given.

PMID- 16645868
TI  - [Transient global amnesia (TGA) during an oral provocation test].
AB  - After the oral administration of the COX 2 inhibitor rofecoxib (Vioxx) as part of
      an oral provocation test, a 64-year-old woman developed acute anterograde and
      retrograde amnesia which lasted for several hours. The patient did not show
      symptoms of anaphylaxis. Neurological examination did not reveal focal symptoms
      or an epileptic seizure. Diffusion-weighted magnetic resonance imaging only
      showed a small region of increased signal intensity in the left hippocampus. The
      patient thus had no anaphylactic drug reaction, but a transient global amnesia
      (TGA) or amnestic episode. TGA is an acute, reversible, cerebral dysfunctional
      state which lasts from 1 h up to maximally 24 h and which is associated with
      anterograde and retrograde amnesia. While about half of the cases appear to occur
      spontaneously, other cases are preceded by physically or emotionally stressful
      events. In our patient it may have been the emotional distress caused by the oral
      provocation testing that has triggered the TGA. When TGA occurs during oral
      challenge of drugs, we recommend repeating the oral challenge of the tested drug.

PMID- 16645869
TI  - Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450
      enzymes.
AB  - OBJECTIVE: Medroxyprogesterone acetate (MPA), frequently used in contraception
      and chemotherapy, was involved in a report of drug-drug interaction (DDI) when co
      administrated with phenytoin, doxifluridine and cyclophosphamide. In order to
      clarify the mechanism of such interaction, an in vitro study was undertaken to
      evaluate MPA's potential to inhibit cytochrome P450 (CYP) enzymes. METHODS:
      Inhibitory effects of MPA on seven CYPs, including CYP1A2, CYP2A6, CYP2C8,
      CYP2C9, CYP2D6, CYP2E1 and CYP3A4, were conducted in human liver microsomes. Time
      and NADPH-dependent inhibitions were also tested. DDI potential was predicted
      according to the [I]/K ( i ) value. RESULTS: MPA was found to inhibit CYP2C9 and
      CYP3A4; half inhibition concentration (IC(50)) was 16.1 microM and 31.5 microM,
      respectively. Slight inhibition was observed on CYP1A2, CYP2A6, CYP2C8 and CYP2D6
      with IC(50) of more than 100 microM. MPA exhibited activation rather than
      inhibition on CYP2E1. Further study revealed that MPA showed a noncompetitive
      inhibition on CYP2C9 and a competitive inhibition on CYP3A4 with K ( i ) of 9.0
      microM and 36 microM, respectively. In addition, MPA was not a mechanism-based
      inhibitor to any of seven isoforms tested. By using predicted concentration of
      MPA in liver, [I]/K ( i ) was estimated to be 0.24 and 0.06 for CYP2C9 and
      CYP3A4, respectively. The concentration of phenytoin co-administrated with MPA
      was calculated to increase by 24%. CONCLUSION: Based on our results, MPA can
      possibly cause clinically relevant DDI via the inhibition of CYP2C9.

PMID- 16645871
TI  - [Severe drug hepatitis caused by Chelidonium].
AB  - We report the case of a 58-year-old male patient who was admitted with severe
      acute cholestatic hepatitis. Liver biopsy showed signs of drug-induced hepatitis.
      Other causes of acute hepatitis were excluded. Therefore, the ingestion of a
      Chelidonium-containing preparation (celandine) was thought to be responsible for
      the hepatitis. Shortly after stopping the administration of Chelidonium, the
      highly pathological levels of several liver parameters began to normalise. As no
      autoantibodies were detectable, an idiosyncratic reaction as the cause of drug
      induced hepatitis is probable. In cases of unknown hepatitis, herbal medications
      should be taken into account as a possible cause.

PMID- 16645876
TI  - The type of visual information mediates eye and hand movement bias when aiming to
      a Muller-Lyer illusion.
AB  - Aiming bias typically influences perception but action towards the illusory
      stimulus is often unaffected. Recent studies, however, have shown that the type
      of information available is a predictor for the expression of action bias. In the
      present cyclical aiming experiment, the type of information (retinal and extra
      retinal) was manipulated in order to investigate the differential contributions
      of different cues on both eye and hand movements. The results showed that a
      Muller-Lyer illusion caused very similar perturbation effects on hand and eye
      movement amplitudes and this bias was mediated by the type of information
      available on-line. Interestingly, the impact of the illusion on goal-directed
      movement was smaller, when information about the figure but not the hand was
      provided for on-line control. Saccadic information did not influence the size of
      the effect of a Muller-Lyer illusion on hand movements. Furthermore, the
      illusions did not alter the eye-hand coordination pattern. The timing of saccade
      termination was strongly linked to hand movement kinematics. The present results
      are not consistent with current dichotomous models of perception and action or
      movement planning and on-line control. Rather, they suggest that the type of
      information available for movement planning mediates the size of the illusory
      effects. Overall, it has been demonstrated that movement planning and control
      processes are versatile operations, which have the ability to adapt to the type
      of information available.

PMID- 16645877
TI  - Long-term results of interstitial brachytherapy (LDR-Brachytherapy) in the
      treatment of patients with prostate cancer.
AB  - Permanent interstitial brachytherapy represents the most conformal form of
      radiation therapy of the prostate and the number of patients with prostate
      cancers treated with permanent radioactive implants is increasing world wide. In
      the meanwhile long-term data on tumor control and treatment morbidity become
      available. Biochemical and clinical tumor control appears to be as effective as
      after radical prostatectomy or external beam radiation therapy in early prostate
      cancer. The risk of postreatment urinary incontinence and bowel dysfunction is
      low and erectile function can be preserved in the majority of patients. However,
      prostate brachytherapy requires a careful selection of patients as pretreatment
      factors predict for long-term outcome. The need for combined modality approaches
      in intermediate and high-risk patients remains controversely discussed. The
      continous refinement of intraoperative planning techniques and the elucidation of
      the etiology of urinary, sexual, and bowel dysfunction should result in further
      improvements in biochemical outcomes and decreased morbidity. Improved and
      standardized postimplantation evaluation will make outcome data more reliable and
      comparable.

PMID- 16645880
TI  - Motion misperception caused by feedback connections: a neural model simulating
      the Frohlich effect.
AB  - When asked to indicate the starting position of a fast moving stimulus, observers
      do not indicate the actual starting position but a later position on the motion
      trajectory. This perceptual illusion is known as the "Frohlich effect". We
      present a neural model aimed at simulating this phenomenon based on feedforward
      and feedback connections. The basic simulation mechanisms seem to be compatible
      with the attentional and the motion extrapolation account. A comparison between
      simulated and empirical results showed that the model is capable of generating
      the same main effects as those found in the empirical data.

PMID- 16645881
TI  - [Minimally invasive total hip arthroplasty. Anterior approach].
AB  - Minimally invasive surgery aims at reducing soft tissue trauma to reduce blood
      loss and postoperative pain, to shorten the necessary stay in hospital, to
      accelerate the rehabilitation and to improve the cosmesis of the scar. The
      article describes the technique of minimally invasive total hip arthroplasty via
      an anterior approach utilizing the interval between the tensor fasciae latae,
      gluteus medius et minimus muscle laterally and the sartorius and rectus femoris
      muscle medially. The proposed method is a safe procedure, which allows correct
      placement of cup and stem. It may be performed within a reasonable time and blood
      loss is low. The procedure leads to cosmetically pleasing scars. As the patients
      usually do not suffer from considerable postoperative pain and experience
      accelerated rehabilitation, they agree to early discharge.

PMID- 16645883
TI  - Fresh frozen plasma and platelet concentrates may increase plasma anti-diphtheria
      toxin IgG concentrations: Implications for diphtheria fusion protein therapy.
AB  - We are developing two fusion proteins consisting of a diphtheria toxin (DT)
      linked to either granulocyte macrophage colony stimulating factor (DT388-GMCSF)
      or interleukin-3 (DT388-IL3). In trials, patients with anti-DT IgG concentrations
      >2.5 microg/ml had significantly lower concentrations of either fusion protein.
      DT389-IL2 is currently FDA approved for the treatment of cutaneous T-cell
      lymphomas. We noted increased concentrations of anti-DT IgG after administration
      of platelet concentrates (PC). Because many of these patients require
      transfusions, we measured the anti-DT IgG content of FFP and PC. We assayed 14
      bags of FFP and 12 bags of single-donor PCs for anti-DT IgG by an
      enzymoimmunoassay against DT389-IL2, DT388-IL3, DT388-GMCSF. The median (percent
      of samples positive) of anti-DT IgG concentrations in PC against DT388-GMCSF,
      DT388-IL3, DT389-IL2 was 0.8 microg/ml (83%), 0.7 microg/ml (83%), and 0.3
      microg/ml (58%), respectively. The median (percent of samples positive) anti-DT
      IgG concentration in FFP against DT388-GMCSF, DT388-IL3, and DT389-IL2 was 2.1
      microg/ml (86%), 1.9 microg/ml (93%), and 1.4 microg/ml (86%), respectively.
      There was a strong association between anti-DT389IL2 IgG, anti-DT388IL3 IgG, and
      anti-DT388GMCSF IgG concentrations in both the FFP (95.6%) and PC (76.3%).
      Assuming a plasma volume of 3 l in a 70 kg patient, a single FFP unit would
      increase the plasma anti-DT389IL2 IgG, anti-DT388IL3 IgG, and anti-DT388GMCSF IgG
      by 0.13 microg/ml, 0.17 microg/ml, and 0.19 microg/ml, respectively. For PC, a
      single unit would increase plasma anti-DT389-IL2 IgG, anti-DT388-IL3 IgG, and
      anti-DT388-GMCSF IgG by 0.03 microg/ml, 0.06 microg/ml, and 0.07 microg/ml,
      respectively. In conclusion, a single FFP or PC appears to minimally increase
      anti-DT IgG concentrations, but multiple units may significantly do such.

PMID- 16645884
TI  - Walter Heiligenberg: the jamming avoidance response and beyond.
AB  - Walter Heiligenberg (1938-1994) was an exceptionally gifted behavioral
      physiologist who made enormous contributions to the analysis of behavior and to
      our understanding of how the brain initiates and controls species-typical
      behavioral patterns. He was distinguished by his rigorous analytical approach
      used in both behavioral studies and neuroethological investigations. Among his
      most significant contributions to neuroethology are a detailed analysis of the
      computational rules governing the jamming avoidance response in weakly electric
      fish and the elucidation of the principal neural pathway involved in neural
      control of this behavior. Based on his work, the jamming avoidance response is
      perhaps the best-understood vertebrate behavior pattern in terms of the
      underlying neural substrate. In addition to this pioneering work, Heiligenberg
      stimulated research in a significant number of other areas of ethology and
      neuroethology, including: the quantitative assessment of aggressivity in cichlid
      fish; the ethological analysis of the stimulus-response relationship in the
      chirping behavior of crickets; the exploration of the neural and endocrine basis
      of communicatory behavior in weakly electric fish; the study of cellular
      mechanisms of neuronal plasticity in the adult fish brain; and the phylogenetic
      analysis of electric fishes using a combination of morphology, electrophysiology,
      and mitochondrial sequence data.

PMID- 16645885
TI  - Sensory acquisition in active sensing systems.
AB  - A defining feature of active sensing is the use of self-generated energy to probe
      the environment. Familiar biological examples include echolocation in bats and
      dolphins and active electrolocation in weakly electric fish. Organisms that
      utilize active sensing systems can potentially exert control over the
      characteristics of the probe energy, such as its intensity, direction, timing,
      and spectral characteristics. This is in contrast to passive sensing systems,
      which rely on extrinsic energy sources that are not directly controllable by the
      organism. The ability to control the probe energy adds a new dimension to the
      task of acquiring relevant information about the environment. Physical and
      ecological constraints confronted by active sensing systems include issues of
      signal propagation, attenuation, speed, energetics, and conspicuousness. These
      constraints influence the type of energy that organisms use to probe the
      environment, the amount of energy devoted to the process, and the way in which
      the nervous system integrates sensory and motor functions for optimizing sensory
      acquisition performance.

PMID- 16645886
TI  - Non-visual environmental imaging and object detection through active
      electrolocation in weakly electric fish.
AB  - Weakly electric fish orient at night by employing active electrolocation. South
      American and African species emit electric signals and perceive the consequences
      of these emissions with epidermal electroreceptors. Objects are detected by
      analyzing the electric images which they project onto the animal's
      electroreceptive skin surface. Electric images depend on size, distance, shape,
      and material of objects and on the morphology of the electric organ and the
      fish's body. It is proposed that the mormyrid Gnathonemus petersii possesses two
      electroreceptive "foveae" at its Schnauzenorgan and its nasal region, both of
      which resemble the visual fovea in the retina of many animals in design,
      function, and behavioral use. Behavioral experiments have shown that G. petersii
      can determine the resistive and capacitive components of an object's complex
      impedance in order to identify prey items during foraging. In addition, fish can
      measure the distance and three-dimensional shape of objects. In order to
      determine object properties during active electrolocation, the fish have to
      determine at least four parameters of the local signal within an object's
      electric image: peak amplitude, maximal slope, image width, and waveform
      distortions. A crucial parameter is the object distance, which is essential for
      unambiguous evaluation of object properties.

PMID- 16645888
TI  - Static and dynamic patient characteristics as predictors of criminal recidivism:
      A prospective study in a Dutch forensic psychiatric sample.
AB  - If clinicians in forensic psychiatry want to reduce risk of reoffending in their
      patients, they require insight into dynamic risk factors, and evidence that these
      add predictive power to static risk indicators. Predictors need to be evaluated
      under clinically realistic circumstances. This study aimed to validate dynamic
      and static variables as predictors of reconviction in a naturalistic outcome
      study. Data on static and dynamic risk factors were collected for 151 patients
      discharged from Dutch forensic psychiatric hospitals. Community follow-up was
      prospective, with a 5.5 year minimum. A prediction model was developed using Cox
      regression analysis. The magnitude of the predictive power of this model was
      estimated using receiver operating characteristic (ROC) analysis. The final
      prediction model contained four static and no dynamic predictors. The model's ROC
      area under the curve was .79 (95% CI .69-.89). Clinical risk ratings were non
      predictive. Post hoc analyses exploring the influence of subgroups of patients
      did not yield better models. It is concluded that a small set of static
      predictors yielded a good estimate of future reconvictions; inclusion of dynamic
      predictors did not add predictive power.

PMID- 16645894
TI  - Epinephrine biosynthesis: hormonal and neural control during stress.
AB  - 1. Stress contributes to the pathophysiology of many diseases, including
      psychiatric disorders, immune dysfunction, nicotine addiction and cardiovascular
      illness. Epinephrine and the glucocorticoids, cortisol and corticosterone, are
      major stress hormones. 2. Release of epinephrine from the adrenal medulla and
      glucocorticoids from the adrenal cortex initiate the biological responses
      permitting the organism to cope with adverse psychological, physiological and
      environmental stressors. Following its massive release during stress, epinephrine
      must be restored to replenish cellular pools and sustain release to maintain the
      heightened awareness and sequelae of responses to re-establish homeostasis and
      ensure survival. 3. Epinephrine is regulated in part through its biosynthesis
      catalyzed by the final enzyme in the catecholamine pathway, phenylethanolamine N
      methyltransferase (E.C. 2.1.1.28, PNMT). PNMT expression, in turn, is controlled
      through hormonal and neural stimuli, which exert their effects on gene
      transcription through protein stability. 4. The pioneering work of Julius Axelrod
      forged the path to our present understanding of how the stress hormone and
      neurotransmitter epinephrine, is regulated, in particular via its biosynthesis by
      PNMT.

PMID- 16645898
TI  - Time spent in the United States and breast cancer screening behaviors among
      ethnically diverse immigrant women: evidence for acculturation?
AB  - The current study was designed to investigate the relations between time spent in
      the United States and breast cancer screening in a large sample (N=915) of
      ethnically diverse immigrant women living in New York City. Previous research
      among Hispanic women has suggested that acculturation positively influences
      health beliefs and preventive health behaviors. However, research has not yet
      extended to other growing immigrant groups, including women from Haiti and the
      English-speaking Caribbean, and has not tested whether time spent in the United
      States differentially impacts breast screening across groups that are known to
      vary in their health beliefs. As expected, time spent in the United States was
      associated with a greater number of mammograms and clinical breast exams.
      Importantly, these relations held even when controlling for (a) age, income,
      education, marital status; (b) morbidity, health insurance, physician's
      recommendation, physical exams; and (c) ethnicity. Moreover, time spent in the
      United States interacted with being Haitian to predict the number of clinical
      breast exams. Even though Haitians were less likely to utilize breast cancer
      screening overall, time spent in the United States had a stronger effect on the
      number of clinical breast exams for Haitian women. Results are discussed in terms
      of the ethnic-specificity of health beliefs, how they may change over time and
      their implications for preventive health behaviors.

PMID- 16645895
TI  - Norlaudanosoline and nicotine increase endogenous ganglionic morphine levels:
      nicotine addiction.
AB  - 1. Given the presence of morphine, its metabolites and precursors, e.g.,
      norlaudanosoline, in mammalian and invertebrate tissues, it became important to
      determine if exposing normal excised ganglia to norlaudanosoline would result in
      increasing endogenous morphine levels. 2. Mytilus edulis pedal ganglia contain
      2.2 +/- 0.41 ng/g wet weight morphine as determined by high pressure liquid
      chromatography coupled to electrochemical detection and radioimmunoassay. 3.
      Incubation of M. edulis pedal ganglia with norlaudanosoline, a morphine
      precursor, resulted in a concentration- and time-dependent statistical increase
      in endogenous morphine levels (6.9 +/- 1.24 ng/g). 4. Injection of animals with
      nicotine also increased endogenous morphine levels in a manner that was
      antagonized by atropine, suggesting that nicotine addiction may be related to
      altering endogenous morphine levels in mammals. 5. We surmise that
      norlaudanosoline is being converted to morphine, demonstrating that invertebrate
      neural tissue can synthesize morphine.

PMID- 16645899
TI  - Gastric H,K-ATPase as a drug target.

PMID- 16645900
TI  - Comparison of HCMV IE and EF-1 promoters for the stable expression of beta
      subunit of hexosaminidase in CHO cell lines.

PMID- 16645901
TI  - Navigating social class roles in community research.
AB  - This paper describes the first author's attempt to collect data in a homeless
      shelter without attending to her role in the social class hierarchy of the
      organization. The author's egalitarian approach towards the homeless clients, and
      her lack of involvement in "staff-only" activities, transgress the social class
      norms within the organizational structure. While the author is successful in
      gaining the trust of the homeless clients, her approach alienates shelter staff,
      especially those in the higher echelons of the social hierarchy. The concepts of
      classism, world views, and Social Identity Theory, are utilized to discuss the
      dilemma faced by researchers who want to challenge, or work outside, a setting's
      status quo.

PMID- 16645902
TI  - Alcohol, tobacco and caffeine use: spouse similarity processes.
AB  - Spouse similarity research has been largely descriptive yet is of theoretical and
      empirical importance to understanding individual differences in substance use.
      The present study considers phenotypic assortment versus social homogamy
      processes for alcohol, tobacco, and caffeine consumption traits using an extended
      twin-spouse design. Whereas both assortment processes were supported for quantity
      of alcohol consumed, phenotypic assortment was supported for quantity of tobacco
      and caffeine consumed, and social homogamy for tobacco use status. Moderate
      heritable influences were found for all traits though no shared environmental
      influences were found beyond those due to social background influences, i.e.
      those pertaining to social homogamy. Swedish government policies in effect at the
      time of marriage selection may explain the presence of social homogamy for
      quantity of alcohol versus quantity of tobacco and caffeine consumed. Social
      homogamy may be more important for some substance use traits such as alcohol
      consumption and tobacco use status but not others.

PMID- 16645903
TI  - Quality of care for depressed elders in post-acute care: variations in needs met
      through services.
AB  - This paper addresses quality of post-acute care for older adults going home after
      hospitalization for depression. Quality was conceptualized and assessed in terms
      of services received for four domains of need: psychiatric, medical, functional,
      and psychosocial. At discharge, needs for care was assessed using medical
      records, standardized instruments, and patient interviews; quality of care was
      assessed by whether or not needs were met by services through the first 6 weeks
      of post-acute care. Quality of care varied across type of need: psychiatric needs
      were most likely, and psychosocial needs were least likely, to be met. Urban
      elders received better psychiatric care than did rural elders. Elders in worse
      physical health received better medical and psychosocial care, but poorer
      psychiatric care. Elders with psychoses and living with others had better care
      for functional dependencies. The competing demands perspective suggests that
      medical illness may take priority over psychiatric care.

PMID- 16645904
TI  - Consumer and case manager perspectives of service empowerment: relationship to
      mental health recovery.
AB  - This study examines the relationship between service empowerment and recovery.
      Service empowerment is defined as the extent to which consumers participate in
      service decisions and the level of reciprocity and respect within the
      relationship with their case managers. Assessments were made from two
      perspectives: consumers and their case managers. Structural equation models were
      developed to examine the direct and indirect effects of service empowerment on
      four recovery outcomes: Quality of Life, Level of Functioning, Consumer-Reported
      Symptomatology, and Case Manager-Reported Symptomatology. Consumers' perceptions
      of service empowerment were the most powerful predictor of recovery outcomes
      across the four models. Consumers' and case managers' perceptions were related
      but the magnitude of the relationship was small, indicating that considerable
      differences exist between their perceptions of service empowerment.

PMID- 16645905
TI  - Organizational management: what service providers are doing while researchers are
      disseminating interventions.
AB  - Much of the recent discussion about how to make interventions with demonstrated
      effectiveness more routinely available to clients emphasizes the role of change
      agents in promoting service providers' use of new interventions. This study
      provides a complimentary perspective; it describes what happens in service
      provider organizations as they go about making changes in the services they
      provide. The data used in this study come from quarterly progress reports of
      participants in the National Child Traumatic Stress Network. The results provide
      a roadmap for anticipating the types of efforts and extent of changes that may
      need to occur for organizations to learn about interventions, form favorable
      opinions toward them, and integrate them into the services they offer.

PMID- 16645906
TI  - Toward the implementation of mental health consumer provider services.
AB  - Encouraged by the New Freedom Commission, mental health systems such as the
      Veteran Administration (VA) are now becoming more recovery-oriented. Consumer
      providers (CPs)--those with serious mental illness who are further along in
      recovery who provide services to others with similar mental health problems--are
      viewed as a key part of this change. However, organizational change theories
      suggest that careful consideration of implementation issues is critical when
      disseminating new and sometimes controversial services into existing
      organizations. Therefore, to guide the dissemination of CP services, the
      literature on the effectiveness of CPs was reviewed, and interviews, focus
      groups, and a brief survey of 110 administrators, providers, and patients were
      conducted at three large VA clinics in Southern California. Questions focused on
      their perceptions of feasibility and acceptability of CP services. Using
      literature and study findings, an organizational change framework and other
      strategies to overcome potential implementation challenges of CP services are
      suggested.

PMID- 16645907
TI  - MHSPY: a children's health initiative for maintaining at-risk youth in the
      community.
AB  - The Massachusetts Mental Health Services Program for Youth (MHSPY) is a home
      based clinical intervention that seeks to maintain youth with severe functional
      impairment in the community via delivery of integrated primary care, mental
      health, substance abuse, and social services. Using blended public agency
      funding, traditional and nontraditional services are provided within a private,
      not-for-profit, managed care organization. Individualized, comprehensive care
      plans are developed by an MHSPY care manager, who works intensively with the
      family and the Care Planning Team to identify needs and resources. Data on
      clinical functioning are collected at baseline and every six months during the
      program. Service utilization and cost are measured on a quarterly basis. Family,
      youth, and agency satisfaction ratings are collected at disenrollment. Aggregate
      analyses based on four years of data show that MHSPY participants have improved
      clinical functioning, including significant reduction in risk to self and others.
      They also experience reduced service utilization and cost and high rates of
      family satisfaction.

PMID- 16645908
TI  - The use of logistic regression to enhance risk assessment and decision making by
      mental health administrators.
AB  - Development of policies and procedures to contend with the risks presented by
      elopement, aggression, and suicidal behaviors are long-standing challenges for
      mental health administrators. Guidance in making such judgments can be obtained
      through the use of a multivariate statistical technique known as logistic
      regression. This procedure can be used to develop a predictive equation that is
      mathematically formulated to use the best combination of predictors, rather than
      considering just one factor at a time. This paper presents an overview of
      logistic regression and its utility in mental health administrative decision
      making. A case example of its application is presented using data on elopements
      from Missouri's long-term state psychiatric hospitals. Ultimately, the use of
      statistical prediction analyses tempered with differential qualitative weighting
      of classification errors can augment decision-making processes in a manner that
      provides guidance and flexibility while wrestling with the complex problem of
      risk assessment and decision making.

PMID- 16645909
TI  - A comparison of mothers with co-occurring disorders and histories of violence
      living with or separated from minor children.
AB  - Data from the Women with Co-occurring Disorders and Histories of Violence Study
      are used to examine characteristics distinguishing mothers currently providing
      care for all their minor children (n = 558) from mothers separated from one or
      more minor children (n = 1396). Mothers are described and compared on background
      characteristics and experiences, well-being and current functioning, situational
      context, and services used. Analyses control for number of children, race, and
      years of education. Mothers separated from children have more children, less
      education, have more often been homeless, in juvenile detention or jail, and have
      lower incomes than mothers living with all their children. Mothers separated from
      children have more extensive experiences of traumatic and stressful life events,
      and the groups differ in current functioning and patterns of services used. While
      cross-sectional data do not allow causal inferences, challenges faced by mothers
      have significant implications for policy and programs.

PMID- 16645910
TI  - Evidence-based treatments in the field: a brief report on provider knowledge,
      implementation, and practice.
AB  - This study examined familiarity, perceived effectiveness, and implementation of
      evidence-based treatments for children in community settings. A sample of service
      providers in agencies affiliated with federal programs to improve children's
      mental health services was identified using a snowball sampling procedure. Forty
      four percent of the sample (n = 616) responded to a Web-based survey designed to
      collect data on evidence-based treatments. High familiarity with, relatively high
      perceived effectiveness, and generally high use of evidence-based treatments were
      reported. Partial implementation of treatment protocols within the context of few
      agency mandates and widely ranging supports for the implementation of evidence
      based treatments was found. Results support the inclusion of more complex models
      of diffusion, dissemination and implementation in research, and development
      efforts for evidence-based treatments.

PMID- 16645911
TI  - Measuring use of health services for at-risk drinkers: how brief can you get?
AB  - This study examines the validity, utility, and costs of using a brief telephone
      administered instrument, the Brief Health Services Questionnaire (BHSQ), for self
      reported health care provider contacts relative to collection and abstraction of
      complete medical records. The study sample was 441 community-dwelling at-risk
      drinkers who participated in an 18-month longitudinal study. Agreement between
      BHSQ self-reports and abstracted provider contacts was good to very good for
      general medical (79% agreement, kappa = .50) and specialty mental health contacts
      (93% agreement, kappa = .62), but low for "other" miscellaneous health contacts
      (61% agreement, kappa = .04). Average cost to collect and abstract complete
      medical records was 424 US dollars per study participant, whereas average cost to
      administer only the BHSQ was 31 US dollars per participant. Although it is not
      possible to conduct a formal cost-effectiveness analysis, results suggest the
      BHSQ is a viable option for collecting self-reported health provider contacts in
      a sample of at-risk drinkers, with definite cost advantages over more elaborate
      data collection methods.

PMID- 16645912
TI  - A neuroscientist-consumer alliance to transform mental health care.
AB  - The field of mental health has long suffered from a lack of convergence of
      disciplines that deal with the mind, the brain, and behavior. This mind-brain
      dualism has been particularly detrimental for consumers and their families who
      daily face stigma and discrimination. The understanding of the brain and its
      dysfunctions has benefited from the study of the human genome and, in particular,
      of the mutations and variations in its code. This analysis permits a better
      understanding of the biological basis of mental disease and will soon inform a
      generation of new diagnostic tools and individualized pharmacological therapies.
      A biological perspective on mental illness will be complemented by the analysis
      of the social factors influencing people's behavior and their impact on brain
      biology and gene function. Neurobiology has progressed to a level for which the
      knowledge that is generated, even if still colored with uncertainty, could
      represent a catalyst for the creation of an alliance between neuroscientists and
      consumers. This partnership has the potential to benefit both parties but will
      require some concrete steps that might be outside of the usual courses of action
      for both consumers and scientists. It is by building collaborations based on
      personal contact and information sharing that a transformation of the mental
      health care system can occur.

PMID- 16645921
TI  - Contrasting soil ciliate species richness and abundance between two tropical
      plant species: a test of the plant effect.
AB  - We still have a rudimentary understanding about the mechanism by which plant
      roots may stimulate soil microbial interactions. A biochemical model involving
      plant-derived biochemical fractions, such as exudates, has been used to explain
      this "rhizosphere effect" on bacteria. However, the variable response of other
      soil microbial groups, such as protozoa, to the rhizosphere suggests that other
      factors could be involved in shaping their communities. Thus, two experiments
      were designed to: (1) determine whether stimulatory and/or inhibiting factors
      associated with particular plant species regulate ciliate diversity and abundance
      and (2) obtain a better understanding about the mechanism by which these plant
      factors operate in the rhizosphere. Bacterial and chemical slurries were
      reciprocally exchanged between two plant species known to differ in terms of
      ciliate species richness and abundance (i.e., Canella winterana and plantation
      Tectona grandis). Analysis of variance showed that the bacteria plus nutrients
      and the nutrients only treatment had no significant effect on overall ciliate
      species richness and abundance when compared to the control treatment. However,
      the use of only colpodean species increased the taxonomic resolution of treatment
      effects revealing that bacterial slurries had a significant effect on colpodean
      ciliate species richness. Thus, for particular rhizosphere ciliates, biological
      properties, such as bacterial diversity or abundance, may have a strong influence
      on their diversity and possibly abundance. These results are consistent with a
      model of soil bacteria-mediated mutualisms between plants and protozoa.

PMID- 16645922
TI  - Ultrastructural analysis of the extracellular matter secreted by the
      psychrotolerant bacterium Pseudoalteromonas antarctica NF3.
AB  - The psychrotolerant strain Pseudoalteromonas antarctica NF3, a Gram-negative
      bacterium isolated from muddy soil samples of Antarctica, secretes large amounts
      of a mucoid exopolymer with a high protein content. It has self-assembly
      properties and capacity to coat and protect liposomes against surfactants. We
      examined the ultrastructure of P. antarctica and the extracellular matter it
      secretes by transmission electron microscopy (TEM) after high-pressure freezing,
      freeze substitution (HPF-FS), and Epon embedding, and compared this with
      information obtained by conventional methods. The improvements brought about by
      HPF-FS to the ultrastructural preservation of the extracellular matter allowed us
      to establish for the first time, in P. antarctica NF3, the presence of two
      components: a large amount of cell-derived outer membrane vesicles containing
      proteins and a capsular polymer around the cells.

PMID- 16645923
TI  - Protozoan grazing increases mineralization of naphthalene in marine sediment.
AB  - Bacterial decomposition of organic matter is frequently enhanced when protozoa
      are present. Various mechanisms have been proposed to account for this
      phenomenon, including effects associated with grazing by protozoa (such as
      increased recycling of limiting nutrients, removal of senescent cells, or
      reduction of competition among bacteria) and indirect effects of grazers (such as
      excretion of bacterial growth factors). Few studies have examined the role of
      protozoa in bacterial degradation of xenobiotic compounds in sediment containing
      a natural community of microbes. The effect of protozoa on mineralization of
      naphthalene was investigated in this study. Laboratory experiments were conducted
      using field-contaminated estuarine sediment, with the indigenous microbial
      populations. Mineralization of naphthalene was up to four times greater in
      treatments with actively grazing protozoa than in treatments containing the
      grazing inhibitor cytochalasin B. Control experiments confirmed that the grazing
      inhibitor was not toxic to ciliates but did prevent them from grazing. The
      grazing inhibitor did not affect growth rates of a mixed culture of sediment
      bacteria or a pure polycyclic-aromatic-hydrocarbon-degrading strain. Once grazing
      had been inhibited, supplementing treatments with inorganic N and P, glucose, or
      additional protozoa failed to stimulate naphthalene mineralization. Naphthalene
      degrading bacteria were four to nine times less abundant when protozoan grazing
      was suppressed. We suggest that protozoa enhance naphthalene mineralization by
      selectively grazing on those sediment bacteria that ordinarily would outcompete
      naphthalene-degrading bacteria.

PMID- 16645924
TI  - Dissolved organic nitrogen release and bacterial activity in the upper layers of
      the Atlantic Ocean.
AB  - The variability of the percentage of extracellular dissolved organic nitrogen
      (DON) release (PER), along with the relationship between DON release and
      bacterioplankton activity, was examined during five oceanographic cruises,
      carried out in the upwelling region of the NW Iberian Peninsula, the SW Bay of
      Biscay, and a latitudinal transect in the Atlantic Ocean (50 degrees N-35 degrees
      S). Rates of nitrogen uptake, DON release, and bacterial production were measured
      at 66 stations and sampled between August 1998 and October 2000. The percentage
      of DON release relative to the gross uptake of ammonium (PERNH4+) ranged from 3
      to 46%, whereas that relative to total nitrogen (NH4+ + NO3- + urea) gross uptake
      (PERtotal) varied between 21 and 82%. The highest values for both PERNH4+ and
      PER(total) were found in oligotrophic oceanic waters (< 0.25 mg chlorophyll a m(
      3)). In oceanic environments, a positive relationship was found between nitrogen
      uptake and DON release rates, with a log-log linear regression slope
      significantly lower than 1, suggesting an inverse relationship between PER and
      gross nitrogen uptake rates. In contrast, in areas with higher productivity
      levels (> 6 mg chlorophyll a m(-3)), such as the continental shelf off the NW
      Iberian Peninsula, PER held constant as nitrogen uptake increased. These results
      suggest the dominance of different processes controlling DON release in oceanic
      and neritic zones. DON release rates accounted for less than 15% of the
      variability observed in bacterial production rates, suggesting a weak response of
      bacterioplankton to phytoplankton on short time scales (hours). Furthermore,
      nitrogen budgets showed an excess of DON release in relation to bacterial
      requirements.

PMID- 16645925
TI  - Denaturing gradient gel electrophoresis can rapidly display the bacterial
      diversity contained in 16S rDNA clone libraries.
AB  - Two different strategies for molecular analysis of bacterial diversity, 16S rDNA
      cloning and denaturing gradient gel electrophoresis (DGGE), were combined into a
      single protocol that took advantage of the best attributes of each: the ability
      of cloning to package DNA sequence information and the ability of DGGE to display
      a community profile. In this combined protocol, polymerase chain reaction
      products from environmental DNA were cloned, and then DGGE was used to screen the
      clone libraries. Both individual clones and pools of randomly selected clones
      were analyzed by DGGE, and these migration patterns were compared to the
      conventional DGGE profile produced directly from environmental DNA. For two
      simple bacterial communities (biofilm from a humics-fed laboratory reactor and
      planktonic bacteria filtered from an urban freshwater pond), pools of 35-50
      clones produced DGGE profiles that contained most of the bands visible in the
      conventional DGGE profiles, indicating that the clone pools were adequate for
      identifying the dominant genotypes. However, DGGE profiles of two different pools
      of 50 clones from a lawn soil clone library were distinctly different from each
      other and from the conventional DGGE profile, indicating that this small number
      of clones poorly represented the bacterial diversity in soil. Individual clones
      with the same apparent DGGE mobility as prominent bands in the humics reactor
      community profiles were sequenced from the clone plasmid DNA rather than from
      bands excised from the gel. Because a longer fragment was cloned (approximately
      1500 bp) than was actually analyzed in DGGE (approximately 350 bp), far more
      sequence information was available using this approach that could have been
      recovered from an excised gel band. This clone/DGGE protocol permitted rapid
      analysis of the microbial diversity in the two moderately complex systems, but
      was limited in its ability to represent the diversity in the soil microbial
      community. Nonetheless, clone/DGGE is a promising strategy for fractionating
      diverse microbial communities into manageable subsets consisting of small pools
      of clones.

PMID- 16645926
TI  - A bioreactor for growth of sulfate-reducing bacteria: online estimation of
      specific growth rate and biomass for the deep-sea hydrothermal vent thermophile
      Thermodesulfatator indicus.

PMID- 16645927
TI  - Microcystins induce morphological and physiological changes in selected
      representative phytoplanktons.
AB  - Dissolved microcystins (MCs) are regularly present in water dominated by
      microcystin-producing, bloom-forming cyanobacteria. In vitro experiments with
      environmentally feasible concentrations (5 x 10(-7) M) of the three most common
      microcystins, MC-LR, MC-RR, and MC-YR, revealed that they influence the
      metabolism of different representative phytoplanktons. At light intensities that
      are close to the cyanobacterial bloom environment (50 micromol m(-2) s(-1)), they
      produce morphological and physiological changes in both microcystin-producing and
      -nonproducing Microcystis aeruginosa strains and also have similar effects on the
      green alga Scenedesmus quadricauda that is frequently present in cyanobacterial
      blooms. All three microcystin variants tested induce cell aggregation, increase
      in cell volume, and overproduction of photosynthetic pigments. All three effects
      appear to be related to each other but are not necessarily caused by the same
      mechanism. The biological activity of microcystins toward the light-harvesting
      complex of photobionts can be interpreted as a signal announcing the worsening of
      light conditions due to the massive proliferation of cyanobacteria. Although the
      function of microcystins is still unknown, it is evident that they have numerous
      effects on phytoplankton in nature. These effects depend on the individual
      organism as well as on the various intracellular and extracellular signaling
      pathways. The fact that dissolved microcystins also influence the physiology of
      microcystin-producing cyanobacteria leads us to the conclusion that the role of
      microcystins in the producing cells differs from the role in the water
      environment.

PMID- 16645928
TI  - Distribution of extensive nifH gene diversity across physical soil
      microenvironments.
AB  - The diversity of nitrogen-fixing bacteria is well described for aquatic
      environments; however, terrestrial analyses remain mostly biased to rhizobial
      plant-microbe associations. We maximized the level of resolution for this study
      through the use of nucleotide sequence information extracted from a series of
      soil microenvironments, ranging from macroaggregates at 2000 microm to the clay
      fraction at < 75 microm in diameter. In addition, we attempted to create an
      overview of the distribution of terrestrial nitrogen fixers across such
      microenvironments by combining culture-independent techniques with a suite of
      natural soil environments from uniquely different origins. Soil diazotroph
      diversity was analyzed phylogenetically for 600 terrestrial nifH sequences from
      12 midsized clone libraries based on microenvironments of three separate soils
      across a global scale. Statistical analyses of nifH gene clone libraries were
      used to estimate coverage, establish degrees of sequence overlap, and compare
      cluster distributions. These analyses revealed an extensive diversity in a
      tropical (19 phylotypes) and an arctic soil (17 phylotypes), and moderate
      diversity in a temperate soil (11 phylotypes). Within each soil, comparisons
      across aggregate size fractions delineated nifH gene cluster shifts within
      populations and degrees of sequence overlap that ranged from significantly
      different (arctic, tropical) to significantly similar (temperate). We suggest
      that this is due to population separation across aggregates of different size
      classes, which results from differences in the temporal stability of aggregates
      as niches for microbial communities. This study not only provides new knowledge
      of the arrangement of diazotrophic communities at the soil microscale, but it
      also contributes to the underrepresented knowledge of soil nifH sequences in the
      public databases.

PMID- 16645929
TI  - Cypris habitat selection facilitated by microbial films influences the vertical
      distribution of subtidal barnacle Balanus trigonus.
AB  - The potential driving force(s) of the vertical distribution of subtidal barnacle
      Balanus trigonus Darwin were investigated using both field and laboratory
      experiments. Early juveniles (approximately 24 h old) placed in intertidal
      [approximately 0.5 m above mean low water level (MLWL)] and subtidal
      (approximately 3 m below MLWL) habitats survived equally well, indicating that
      the intertidal absence of B. trigonus in Hong Kong waters was not determined by
      differential mortality. However, enhanced attachment of cyprids in subtidal
      habitats indicated the importance of differential larval choice in determining
      their vertical distribution. In the laboratory, cyprids preferred to attach in
      response to subtidal microbial films, which may implicate microbial films as a
      primary cue in driving the adult vertical distribution. Microbial films developed
      in these two habitats differed in their biomass (= total organic carbon),
      abundance of bacteria and diatoms (determined by fluorescence microscopy), and
      bacterial diversity (determined by DNA fingerprinting analysis). For example, 6
      day films in subtidal habitat had a significantly higher biomass than in films
      from intertidal habitat (P < 0.05). There was no difference in the biomass of
      films from these two habitats in 9-day films (P > 0.05); however, bacterial
      abundance was greater in subtidal films than in intertidal films, irrespective of
      the age of the film, although there was no difference in diatom abundance in
      films from these two habitats. Neither the abundance of bacteria and diatoms nor
      the biomass correlated with the attachment preferences of cyprids. This study has
      not provided any data to prove the existence of inductive and inhibitive (to
      cyprid attachment) bacterial species in subtidal and intertidal films,
      respectively; however, results indicate that bacterial community provided
      qualitative information that might explain the preferential attachment of B.
      trigonus cyprids in subtidal habitat.

PMID- 16645934
TI  - 1H HR-MAS NMR of carotenoids in aqueous samples and raw vegetables.
AB  - Carotenoids are linear C40 tetraterpenoid hydrocarbons and represent a wide
      category of natural pigments. They are components of the pigment system of
      chloroplasts and are involved in the primary light absorption and the photon
      canalization of photosynthesis. Moreover, they also behave as quenchers of
      singlet oxygen, protecting cells and organisms against lipid peroxidation.
      Carotenoids have a strong lipophilic character and are usually analyzed in
      organic solvents. However, because of their biological activity, the
      characterization of these compounds in an aqueous environment or in the natural
      matrix is very important. One of the most important dietary carotenoids is beta
      carotene, which has been extensively studied both in vivo and in model systems,
      but because of the low concentration and strong interaction with the biological
      matrix, beta-carotene has never been observed by NMR in solid aqueous samples.In
      the present work, a model system has been developed for the detection and
      identification of beta-carotene in solid aqueous samples by 1H HR-MAS NMR. The
      efficiency of the model has led to the identification of beta-carotene in a raw
      vegetable matrix.

PMID- 16645935
TI  - Complete assignments of 1H and 13C NMR spectra of leucanthoside A, a new
      triterpenoid saponin from Cephalaria leucantha L.
AB  - Leucanthoside A, a new allose-containing triterpenoid saponin (1), was isolated
      from the aerial parts of Cephalaria leucantha L. Its structure was determined by
      electrospray ionization mass spectrometry and NMR spectroscopy. Complete
      assignments of the 1H and 13C NMR chemical shifts were achieved by two
      dimensional NMR experiments: DQF-COSY, NOESY, TOCSY, HSQC, DINE-HSQC, HMBC, 13C
      1H 2D-J-resolved spectroscopy, and 1,1-ADEQUATE.

PMID- 16645936
TI  - A population-based study of the association between coronary artery bypass graft
      surgery (CABG) and cognitive decline: the Cache County study.
AB  - BACKGROUND: The relationship between coronary artery bypass graft (CABG) surgery
      and cognitive decline remains uncertain, in particular with regard to whether
      there is delayed cognitive decline associated with this procedure. METHODS: This
      was a population-based cohort study involving participants in the Cache County
      Study of Memory Health and Aging. At baseline the study enrolled 5,092 persons
      age 65 and older and followed them up three years later and again four years
      after that. Individuals who reported having undergone CABG surgery at study
      baseline or had this surgery in between follow-up waves were compared to
      individuals who never reported having the surgery. The main outcome measure was
      the Modified Mini Mental State (3MS). Multilevel models were used to examine the
      relationship between CABG surgery and cognitive decline over time. RESULTS: Study
      participants who had CABG surgery evidenced 0.95 points of greater decline
      relative to baseline on the 3MS at the first follow-up interview after CABG, and
      an average of 1.9 points of greater decline at the second follow-up interview,
      than those without CABG (t = -2.51, df = 2,316, p = 0.0121), after adjusting for
      several covariates, including number of vascular conditions. This decline was
      restricted to individuals who were more than five years past the procedure and
      was not evident in the early years after the surgery. CONCLUSIONS: CABG surgery
      is associated with accelerated cognitive decline more than five years after the
      procedure in a long-lived population. This decline is small and its clinical
      significance is uncertain. We could not find an association between CABG and
      decline in the first five post-operative years.

PMID- 16645937
TI  - Deliberate self-harm in people aged 60 years and over: characteristics and
      outcome of a 20-year cohort.
AB  - BACKGROUND: Little information is available about older deliberate self-harm
      (DSH) patients and their outcome. METHODS: This study is a prospective
      investigation and follow-up of 730 consecutive patients (459 females and 271
      males) aged 60 years and over who presented to a general hospital following DSH
      over a 20-year period, 1978-1997. Outcome has been examined in terms of
      repetition of DSH, and deaths by the end of 2000 identified through official
      death registers. RESULTS: DSH involved self-poisoning in 88.6% of cases, 49.3% of
      the overdoses including paracetamol (acetaminophen), 24.0% minor tranquillizers,
      and 15.9% antidepressants. Nearly three-quarters of episodes involved high
      suicidal intent. Common problems preceding DSH were physical illness (46.1%),
      social isolation (33.5%), relationship problems with family (29.4%) or partner
      (25.9%), and bereavement or loss (16.7%). Repetition of DSH occurred in 15.3% of
      cases, 8.2% in the first year following DSH. By the end of 2000, 432/661 (65.4%)
      of traced patients had died. There were 30 suicides and open verdicts, which were
      49 times and 33 times more frequent respectively than expected from general
      population death rates. Prior DSH before initial presentation was the main risk
      factor for suicide, with some evidence of high suicide intent being another
      factor. There were also excess deaths due to several types of physical disorder.
      CONCLUSIONS: DSH in older people is closely related to suicide, both in terms of
      suicidal intent and risk of eventual suicide, especially when DSH is repeated.
      The range of problems experienced by older DSH patients requires extensive and
      multidisciplinary clinical interventions.

PMID- 16645938
TI  - The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a
      study of micronutrients and cognitive function in a homebound elderly population.
AB  - BACKGROUND: Micronutrient status can affect cognitive function in the elderly;
      however, there is much to learn about the precise effects. Understanding
      mediating factors by which micronutrient status affects cognitive function would
      contribute to elders' quality of life and their ability to remain in the home.
      OBJECTIVES: The Nutrition, Aging, and Memory in Elders (NAME) Study is designed
      to advance the current level of knowledge by investigating potential mediating
      factors by which micronutrient status contributes to cognitive impairment and
      central nervous system abnormalities in the elderly. NAME targets homebound
      elders because they are understudied and particularly at risk for poor
      nutritional status. METHODS: Subjects are community-based elders aged 60 and
      older, recruited through area Aging Services Access Points. The NAME core data
      include demographics; neuropsychological testing and activities of daily living
      measures; food frequency, health and behavioral questionnaires; anthropometrics;
      gene status; plasma micronutrients, homocysteine, and other blood determinants. A
      neurological examination, psychiatric examination, and brain MRI and volumetric
      measurements are obtained from a sub-sample. RESULTS: Preliminary data from first
      300 subjects are reported. These data show that the NAME protocol is feasible and
      that the enrolled subjects are racially diverse, at-risk, and had similar basic
      demographics to the population from which they were drawn. CONCLUSION: The goal
      of the NAME study is to evaluate novel relationships between nutritional factors
      and cognitive impairment. These data may provide important information on
      potential new therapeutic strategies and supplementation standards for the
      elderly to maintain cognitive function and potentially reduce the public health
      costs of dementia.

PMID- 16645939
TI  - Correlational study of the Chinese version of the executive interview (C-EXIT25)
      to other cognitive measures in a psychogeriatric population in Hong Kong Chinese.
AB  - OBJECTIVES: This study is designed to pilot test the feasibility and
      correlational properties of the adapted Chinese version of Executive Interview (C
      EXIT25) to other cognitive measures in a psychogeriatric population in Hong Kong
      Chinese. METHOD: Eighty-five community dwelling elders from different levels of
      residential care facilities were assessed with C-EXIT25, Cantonese version of
      Mini-Mental State Examination (C-MMSE), Chinese version of Mattis Dementia Rating
      Scale (CDRS) and Nelson's Modified Card Sorting Test (MCST). RESULTS: The C
      EXIT25 has high internal consistency (Cronbach's alpha = 0.7995) and inter-rater
      reliability (r = 0.91). The C-EXIT25 has superior correlational property to
      performance indices of MCST than the C-MMSE and CDRS, after adjusting for age,
      gender and educational level. It also discriminates among subjects at different
      stages on Clinical Dementia Rating. CONCLUSIONS: The C-EXIT25 is a potentially
      feasible and valid bedside tool for assessment of executive cognitive functions
      in the psychogeriatric population in Hong Kong Chinese.

PMID- 16645940
TI  - Nonaqueous versus aqueous capillary electrophoresis of alpha-helical
      polypeptides: effect of secondary structure on separation selectivity.
AB  - The CE separation of alpha-helical polypeptides composed of 14-31 amino acid
      residues has been investigated using aqueous and nonaqueous BGEs. The running
      buffers were optimized with respect to pH. Generally, higher separation
      selectivities were observed in nonaqueous electrolytes. This may be explained by
      a change in the secondary structure when changing from water to organic solvents.
      Circular dichroism spectra revealed a significant increase in helical structures
      in methanol-based buffers compared to aqueous buffers. This change in secondary
      structure of the polypeptides contributed primarily to the different separation
      selectivity observed in aqueous CE and NACE. For small oligopeptides of two to
      five amino acid residues no significant effect of the solvent was observed in
      some cases while in other cases a reversal of the migration order occurred when
      changing from aqueous to nonaqueous buffers. As these peptides cannot adopt
      secondary structures the effect may be attributed to a shift of the pKa values in
      organic solvents compared to water.

PMID- 16645941
TI  - A simple light-emitted diode-induced fluorescence detector using optical fibers
      and a charged coupled device for direct and indirect capillary electrophoresis
      methods.
AB  - We constructed a simple fluorescence detector for both direct and indirect CE
      methods using a blue light-emitted diode (470 nm) as excitation source, a
      bifurcated optical fiber as a waveguide, and a CCD camera as a detector. The
      connection of all the components is fairly easy even for nonexperts and the use
      of a CCD camera improves the applicability of this detector compared to the
      others using PMTs because it permits the recording of 2-D electropherograms or
      phosphorescence measurements. This detector provides a compact, low cost, and
      rapid system for the determination of native fluorescence compounds which have
      high quantum yields by CE with direct fluorescence detection, showing an LOD of
      2.6 x 10(-6) M for fluorescein; the determination of fluorescence derivative
      compounds by CE with direct fluorescence detection, showing an LOD of 1.6 x 10(
      7) M for FITC-labeled 1,6-diaminohexane; and nonfluorescence compounds by CE with
      indirect fluorescence detection with an LOD of 2.7 x 10(-6) M for gallic acid.

PMID- 16645942
TI  - Rapid detection of Staphylococcus aureus by a combination of monoclonal antibody
      coated latex and capillary electrophoresis.
AB  - The rapid detection of pathogenic bacteria is extremely important in
      biotechnology and clinical diagnosis. CE has been utilized in the field of
      bacterial analysis for many years, but to some extent, simultaneous separation
      and identification of certain microbes from complex samples by CE coupled with UV
      detector is still a challenge. In this paper, we propose a new strategy for rapid
      separation and identification of Staphylococcus aureus (S. aureus) in bacterial
      mixtures by means of specific mAb-coated latex coupled with CZE. An appropriate
      set of conditions that selectively isolated S. aureus from the microorganisms
      Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were
      established. S. aureus could be differentiated from the others by unique peaks in
      the electropherograms. The validity was also confirmed by LIF with antibodies
      specific to both the latex and the microbial cells. The LOD is as low as 9.0 x
      10(5) colony forming unit/mL. We have also utilized this technology to identify
      S. aureus in a stool sample coming from a healthy volunteer spiked successfully
      with S. aureus. This CZE-UV technique can be applied to rapid diagnosis of
      enteritis caused by S. aureus or other bacterial control-related fields needing
      rapid identification of target pathogens from microbial mixtures. In theory, this
      method is suitable for the detection of any bacterium as long as corresponding
      bacterium-specific antibody-coated latex is available.

PMID- 16645943
TI  - Study on pharmacokinetics and tissue distribution of norvancomycin in rats by CE
      with electrochemical detection.
AB  - In this paper, we developed a sensitive and simple method to study the
      pharmacokinetics and tissue distribution of norvancomycin (NVCM) in experimental
      animals by using CE with electrochemical detection. Pharmacokinetics
      investigation was performed by the collection of blood samples at timed intervals
      following administration of NVCM. Pharmacokinetic parameters were calculated by
      the 3P87 pharmacokinetic program. The elimination half-life of NVCM was 42.4742
      min with a clearance rate of 0.0233 mL x kg(-1) x min(-1). Additionally, drug
      distribution was studied by measuring the NVCM levels in kidney, lung, stomach,
      intestine, spleen, heart, liver, and cerebrum. Electrophoresis conditions such as
      buffer solution, working potential, separation voltage, and sampling time were
      also discussed. The linear range was from 0.8 to 540 microg/mL with a correlation
      coefficient of 0.9991. The detection limit was 0.3 microg/mL. This method was for
      the first time applied to study the pharmacokinetics and tissue distributions of
      NVCM in experimental animals.

PMID- 16645944
TI  - Unconventional detection methods for microfluidic devices.
AB  - The direction of modern analytical techniques is to push for lower detection
      limits, improved selectivity and sensitivity, faster analysis time, higher
      throughput, and more inexpensive analysis systems with ever-decreasing sample
      volumes. These very ambitious goals are exacerbated by the need to reduce the
      overall size of the device and the instrumentation - the quest for functional
      micrototal analysis systems epitomizes this. Microfluidic devices fabricated in
      glass, and more recently, in a variety of polymers, brings us a step closer to
      being able to achieve these stringent goals and to realize the economical
      fabrication of sophisticated instrumentation. However, this places a significant
      burden on the detection systems associated with microchip-based analysis systems.
      There is a need for a universal detector that can efficiently detect sample
      analytes in real time and with minimal sample manipulation steps, such as lengthy
      labeling protocols. This review highlights the advances in uncommon or less
      frequently used detection methods associated with microfluidic devices. As a
      result, the three most common methods - LIF, electrochemical, and mass
      spectrometric techniques - are omitted in order to focus on the more esoteric
      detection methods reported in the literature over the last 2 years.

PMID- 16645945
TI  - Functionalized magnetic micro- and nanoparticles: optimization and application to
      micro-chip tryptic digestion.
AB  - The preparation of an easily replaceable protease microreactor for micro-chip
      application is described. Magnetic particles coated with poly(N
      isopropylacrylamide), polystyrene, poly(2-hydroxyethyl methacrylate-co-ethylene
      dimethacrylate), poly(glycidyl methacrylate), [(2-amino
      ethyl)hydroxymethylen]biphosphonic acid, or alginic acid with immobilized trypsin
      were utilized for heterogeneous digestion. The properties were optimized, with
      the constraint of allowing immobilization in a microchannel by a magnetic field
      gradient. To obtain the highest digestion efficiency, sub-micrometer spheres were
      organized by an inhomogeneous external magnetic field perpendicularly to the
      direction of the channel. Kinetic parameters of the enzyme reactor immobilized in
      micro-chip capillary (micro-chip immobilized magnetic enzyme reactor (IMER)) were
      determined. The capability of the proteolytic reactor was demonstrated by five
      model (glyco)proteins ranging in molecular mass from 4.3 to 150 kDa. Digestion
      efficiency of proteins in various conformations was investigated using SDS-PAGE,
      HPCE, RP-HPLC, and MS. The compatibility of the micro-chip IMER system with total
      and limited proteolysis of high-molecular-weight (glyco)proteins was confirmed.
      It opens the route to automated, high-throughput proteomic micro-chip devices.

PMID- 16645947
TI  - Free-solution electrophoresis of DNA modified with drag-tags at both ends.
AB  - In end-labeled free-solution electrophoresis (ELFSE), DNA molecules are labeled
      with a frictional modifier or "drag-tag", allowing their size-based
      electrophoretic separation in free solution. Among the interesting observations
      from early work with dsDNA using streptavidin as a drag-tag was that the drag
      induced by including a streptavidin label at both ends was significantly more
      than double that from a single streptavidin (Heller, C. et al.., J. Chromatogr. A
      1998, 806, 113-121). This finding was assumed to be in error, and subsequent work
      focused on experiments in which only a single drag-tag is appended to one end of
      the DNA molecule. Recent theoretical work (McCormick, L. C., Slater, G. W.,
      Electrophoresis 2005, 26, 1659-1667) has examined the contribution of end-effects
      to the free-solution electrophoretic mobility of charged-uncharged polymer
      conjugates, reopening the question of enhanced drag from placing a drag-tag at
      both ends. In this study, this effect is investigated experimentally, using
      custom-synthesized ssDNA oligonucleotides allowing the attachment of drag-tags to
      one or both ends, as well as dsDNA PCR products generated with primers
      appropriate for the attachment of drag-tags at one or both ends. A range of sizes
      of drag-tags are used, including synthetic polypeptoid drag-tags as well as
      genetically engineered protein polymer drag-tags. The enhanced drag arising from
      labeling both ends has been confirmed, with 6-9% additional drag for the ssDNA
      and 10-23% additional drag for the dsDNA arising from labeling both ends than
      would be expected from simply doubling the size of the drag-tag at one end. The
      experimental results for ssDNA labeled at both ends are compared to the
      predictions of the recent theory of end-effects, with reasonably good
      quantitative agreement. These experimental findings demonstrate the feasibility
      of enhancing ELFSE separations by labeling both ends of the DNA molecule, leading
      to greater resolving power and a wider range of applications for this technique.

PMID- 16645948
TI  - Intramolecular controls for the generation of clinical-quality SNP genotypes and
      the assessment of normal heterozygote imbalance.
AB  - We present an inventive method that generates intramolecular controls for SNP
      analysis, termed Mirror SNPs. Using the ovine diseases of callipyge and scrapie
      as examples, we describe the PCR-driven production of balanced heterozygote
      copies of the various SNPs implicated in these diseases. In the absence of a
      callipyge-positive control DNA, we generated a balanced heterozygote Mirror SNP
      that represents both the wild-type and mutant forms of the causal polymorphism.
      Simultaneous analysis of this artificial Mirror SNP and the Real (target) SNP was
      used to prove the absence of the mutant form of the nucleotide at the Real SNP
      position in tested samples. Scrapie susceptibility was assessed using a PCR
      driven system which generated four separate Mirror SNPs, and these enabled the
      confirmation of an apparent departure from 'balanced' heterozygote appearance at
      Real SNPs tested. Mirror SNP technology is generic and will enable the accurate
      assessment of rare and medically important SNP variants, more accurate frequency
      determinations, and the potential assessment of SNPs in 'mixed template' samples
      common in forensic analyses.

PMID- 16645949
TI  - Isolation, identification and characterisation of starch-interacting proteins by
      2-D affinity electrophoresis.
AB  - A 2-D affinity electrophoretic technique (2-DAE) has been used to isolate
      proteins that interact with various starch components from total barley endosperm
      extracts. In the first dimension, proteins are separated by native PAGE. The
      second-dimensional gel contains polysaccharides such as amylopectin and glycogen.
      The migration of starch-interacting proteins in this dimension is determined by
      their affinity towards a particular polysaccharide and these proteins are
      therefore spatially separated from the bulk of proteins in the crude extract.
      Four distinct proteins demonstrate significant affinity for amylopectin and have
      been identified as starch branching enzyme I (SBEI), starch branching enzyme IIa
      (SBEIIa), SBEIIb and starch phosphorylase using polyclonal antibodies and
      zymogram activity analysis. In the case of starch phosphorylase, a protein spot
      was excised from a 2-DAE polyacrylamide gel and analysed using Q-TOF MS/MS,
      resulting in the alignment of three internal peptide sequences with the known
      sequence of the wheat plastidic starch phosphorylase isoform. This assignment was
      confirmed by the determination of the enzyme's function using zymogram analysis.
      Dissociation constants (Kd) were calculated for the three enzymes at 4 degrees C
      and values of 0.20, 0.21 and 1.3 g/L were determined for SBEI, SBEIIa and starch
      phosphorylase, respectively. Starch synthase I could also be resolved from the
      other proteins in the presence of glycogen and its identity was confirmed using a
      polyclonal antibody and by activity analysis. The 2-DAE method described here is
      simple, though powerful, enabling protein separation from crude extracts on the
      basis of function.

PMID- 16645950
TI  - Breast cancer proteomics by laser capture microdissection, sample pooling, 54-cm
      IPG IEF, and differential iodine radioisotope detection.
AB  - The presence of progesterone receptor (PR) in estrogen receptor (ER)-positive
      breast cancer is associated with a good prognosis, and indicates that tumors are
      likely to respond to tamoxifen. However, ER+/PR- tumors respond less well. To
      reveal the potential molecular mechanism of this phenomenon, we sought to
      identify differential protein abundances between invasive ductal carcinoma cells
      from cryopreserved ER+/PR+ and ER+/PR- mammary tumor specimens. Because current
      proteomics methods are hampered in the examination of most primary human tumor
      samples by the extreme tissue heterogeneity, we used laser capture
      microdissection (LCM) to isolate tumor cells and developed a sample pooling
      strategy to analyze small sample protein lysates. Proteins from LCM-harvested
      tumors were pooled into four sub-pools from each condition of three tumors/sub
      pool, and proteins from respective paired sub-pools were co-electrophoresed by 2
      DE using 54-cm IEF over pH 4-9. Abundance ratios were accurately quantified by a
      differential multiplex radioactive ProteoTope method at low attomole levels (
      approximately 3.6 microg protein per labeling reaction, <180 ng per multiplex
      protein sample per 54-cm gel). Applying this approach, differentially displayed
      proteins were identified by MS using comigrating non-radioactively labeled tumor
      proteins. They include decreased cytochrome b5 and transgelin, and more abundant
      CRABP-II, cyclophilin A, Neudesin, and hemoglobin in ER+/PR+ tumors versus ER+/PR
      providing a possible explanation for differential susceptibility against
      tamoxifen as a result of deregulated cytochrome b5-dependent metabolism. This
      study demonstrates the potential of ProteoTope and LCM to enable extremely
      sensitive and precise differential analyses from well-defined primary clinical
      specimen.

PMID- 16645953
TI  - Determination of thyroxine in pharmaceuticals using flow injection with luminol
      chemiluminescence inhibition detection.
AB  - A simple flow injection method is reported for the determination of thyroxine,
      based on its inhibition effect on luminol-iron(II) chemiluminescence in alkaline
      medium in the presence of molecular oxygen. The detection limits (2s) for d- and
      l-thyroxine are 0.08 and 0.1 mg/L, respectively, with a sample throughput of
      100/h. The calibration data for d- and l-thyroxine over the range 0.2-1.0 mg/L
      gives correlation coefficients (r(2)) of 0.9915 and 0.984 with relative standard
      deviations (RSD; n = 4) in the range 1.2-2.8%. The effects of some organic
      compounds was studied on luminol-iron(II) CL system for thyroxine determination.
      The method was applied to pharmaceutical thyroxine tablets and the results
      obtained (in the range 50.5 +/- 2.0-51.6 +/- 1.2 microg l-thyroxine/tablet) were
      in reasonable agreement with the value quoted.

PMID- 16645954
TI  - On-line preparation of peroxymonocarbonate and its application for the study of
      energy transfer chemiluminescence to lanthanide inorganic coordinate complexes.
AB  - It has been shown that peroxymonocarbonate ion (HCO(4) (-)) is a potent oxidant.
      In this study, a flow-injection system was developed in order to prepare on-line
      HCO(4) (-) ion and the optimum conditions for the on-line preparation of HCO(4) (
      ) were studied in detail. We used 99% (13)C-enriched NaHCO(3) to examine
      peroxymonocarbonate by (13)C-NMR at 25 degrees C. An ultra-weak chemiluminescence
      (CL) was observed after mixing H(2)O(2) and sodium bicarbonate in an organic co
      solvent that can accelerate the formation of HCO(4) (-) ion. When lanthanide
      inorganic coordinate complex, Eu(II)-EDTA, was added into this HCO(4) (-) system,
      the CL intensity was significantly enhanced. The CL mechanism was investigated by
      various methods. The experimental results indicate that peroxymonocarbonate
      oxidizes Eu(II) to Eu(III) and produces singlet oxygen; meanwhile, the energy
      originating from dimers of singlet oxygen is accepted by the Eu(III)-EDTA(-)
      complex. The excited Eu(III) ions undergo radiative deactivation and emit CL.

PMID- 16645955
TI  - Improvement of the acridine orange-protein-surfactant system for protein
      estimation based on aromatic ring stacking effect of sodium dodecyl benzene
      sulphonate.
AB  - The fluorescence of acridine orange (AO) is greatly quenched by the anionic
      surfactant sodium dodecyl benzene sulphonate (SDBS), but when protein is added
      into the AO-SDBS system, the fluorescence intensity of the latter is enhanced
      again. Based on this, a new fluorimetric method of determination of protein was
      developed. Under optimum conditions, the enhanced intensity of fluorescence is in
      proportion to the concentration of protein, such as bovine serum albumin (BSA),
      human serum albumin (HSA) and egg albumin (EA), over a wide range with detection
      limits at the 10(-9) g/mL level. This method has been satisfactorily used for the
      determination of protein in samples. We compared results using 280 nm and 490 nm
      excitation wavelengths and the mechanism of the assay.

PMID- 16645956
TI  - Inhibition and enhancement by organic compounds of luminol-KIO4-H2O2
      chemiluminescence.
AB  - The effects of 36 organic compounds on luminol-KIO(4)-H(2)O(2) chemiluminescence
      (CL) were studied. It was found that most of the tested compounds could inhibit
      or enhance the CL intensity. The activities of such inhibitors or enhancers were
      related to the pH of the CL system and the number and position of functional
      groups such as -OH and -NH(2) on aromatic rings. The mechanism of the CL
      inhibition and enhancement was considered. Based on the CL inhibition or
      enhancement, the possibility of analytical applications was explored. The results
      demonstrated that numerous compounds were detectable at the ng/mL level using the
      CL system.

PMID- 16645957
TI  - The sensitive determination of nucleic acids using a fluorescence-quenching
      method.
AB  - Experiments indicated that nucleic acids can quench the fluorescence of the Eu3+ 
      2-thenoyltrifluoroacetone (TTA)-1,10-phenanthroline (Phen) system. Based on this,
      a sensitive method for the determination of nucleic acids was proposed. The
      experiments indicated that under the optimum conditions, the quenched
      fluorescence intensity was in proportion to the concentration of nucleic acids in
      the range 1.0 x 10(-11)-1.0 x 10(-6) g/mL for yeast RNA (yRNA), 5.0 x 10(-11)-5.0
      x 10(-7) g/mL for fish sperm (fsDNA) and 1.0 x 10(-10)-1.5 x 10(-6) g/mL for calf
      thymus DNA (ctDNA). Their detection limits were 3.0 x 10(-12), 4.0 x 10(-12) and
      5.0 x 10(-11) g/mL, respectively. Therefore, the proposed method is one of the
      most sensitive methods available. The interaction between nucleic acids and Eu3+ 
      TTA-Phen is also discussed.

PMID- 16645958
TI  - Evaluation of 31P high-resolution magic angle spinning of intact tissue samples.
AB  - The first detailed evaluation is presented of high-resolution (31)P MRS using
      magic angle spinning (MAS) of intact tissue samples and comparison with the
      conventional method of studying tissue extracts. The main motivation is that MAS
      leaves the sample intact at the end of the study for histopathological
      evaluation. While MAS of tissue samples has previously been demonstrated for (1)H
      MRS, (31)P MRS is better suited to study of the phospholipid metabolites of
      importance in cancer. Samples of rhabdomyosarcoma and RIF-1 experimental tumours
      were maintained at 4 degrees C, spun at 3 kHz and measured in 28-min acquisitions
      at 11.7 and 14 T. Metabolite stability was evaluated using four sequential 28-min
      acquisitions. High-resolution MRS was performed on extracts of the same tissue
      samples. (31)P HR-MAS yielded well-resolved high-resolution spectra, showing
      peaks from phosphoethanolamine (PE), phosphocholine (PC), inorganic phosphate,
      glycerophosphoethanolamine and glycerophosphocholine, with linewidths in the
      range 3-20 Hz. In tumour samples there was no significant change in peak areas
      over a 2-h period, while peaks sensitive to pH (inorganic phosphate, PE and PC)
      showed a small change in chemical shift, corresponding to a change of 0.13 +/-
      0.06 pH units. Tissue metabolite concentrations showed good agreement with
      concentrations measured from extracts of the same pieces of tissue. For
      calculation of metabolite concentrations, the measurement of a reference compound
      in a separate measurement is more robust than using the signal from a reference
      compound in the rotor with the sample. Compared with performing tissue extracts,
      use of MAS of intact tissue samples requires less preparation, is quicker and
      permits the same sample to be used for subsequent histopathology. The methodology
      has particular application in studying phospholipid metabolism in cancer and in
      monitoring tumour response to treatment, where concentrations of phospholipid
      related metabolites are found to alter following response to a wide range of anti
      cancer therapies.

PMID- 16645959
TI  - A comparison of the presumptive luminol test for blood with four non
      chemiluminescent forensic techniques.
AB  - Presumptive blood detection tests are used by forensic investigators to detect
      trace amounts of blood or to investigate suspicious stains. Through the years, a
      number of articles have been published on the popular techniques of the day.
      However, there is no single paper that critiques and compares the five most
      common presumptive blood detection tests currently in use: luminol,
      phenolphthalein (Kastle-Meyer), leucomalachite green, Hemastix and the forensic
      light source. The present authors aimed to compare the above techniques with
      regard to their sensitivity, ease of use and safety. The luminol test was
      determined to be the most sensitive of the techniques, while Hemastix is a
      suitable alternative when the luminol test is not appropriate.

PMID- 16645960
TI  - Alteration of monocytic cell oxidative burst caused by methacrylic monomers
      present in dental materials: a chemiluminescence study.
AB  - Methacrylates are present in dental composite resins used in clinical practice.
      Methacrylates are photo-polymerized, but this reaction is never complete, so
      release of uncured monomers in the periapical tissues and in biological fluids
      may happen and, potentially, alter the repair of pulpal and of periapical lesions
      by interfering with local phagocytes. The aim of this study was the evaluation of
      the functional activity of the monocyte-macrophage system after incubation with
      methacrylic monomers. The oxidative burst of two cellular systems was analysed
      using the chemiluminescence technique. Data were collected and statistically
      analysed. Monomers were found to reduce the in vitro oxidative burst of
      phagocytes independently from their cytotoxicity. These findings demand further
      evaluation of the effects of oxidative burst alteration in monocyte-macrophage
      function and may prompt the inclusion of the described chemiluminescence test in
      biocompatibility preliminary studies of dental materials.

PMID- 16645961
TI  - Determination of iodide using flow injection with acidic potassium permanganate
      chemiluminescence detection.
AB  - A simple and rapid flow-injection method is described for the determination of
      iodide, based on potassium permanganate chemiluminescence detection via oxidation
      of formaldehyde in aqueous hydrochloric acid. The calibration graph was linear
      over the range 1.0-12 x 10(-6) mol/L (r2 = 0.9955) with relative standard
      deviations (n = 4) in the range 1.0-3.5%. The detection limit (3sigma) was 1.0 x
      10(-7) mol/L, with sample throughput of 120/h. The effect of interfering cations
      [Ca(II), Mg(II), Ni(II), Fe(II), Fe(III) and Pb(II)] and anions (Cl-, SO4(2-),
      PO4(3-), NO3-, NO2-, F- and SO3(2-)) were studied. The method was applied to
      iodized salt samples and the results obtained in the range 0.03 +/- 0.005 - 0.10
      +/- 0.006 mg I/g were in reasonable agreement with the amount labelled. The
      method was statistically compared with the results obtained by titration; no
      significant disagreement at 95% confidence was observed.

PMID- 16645962
TI  - Protein-protein interactions in actin-myosin binding and structural effects of
      R405Q mutation: a molecular dynamics study.
AB  - Detailed residue-wise interactions involved in the binding of myosin to actin in
      the rigor conformation without nucleotides have been examined using molecular
      dynamics simulations of the chicken skeletal myosin head complexed with two actin
      monomers, based on the cryo-microscopic model of Holmes et al. (Nature
      2003;425:423-427). The overall interaction is largely electrostatic in nature,
      because of the charged residues in the four loops surrounding the central primary
      binding site. The 50k/20k loop, disordered in crystal structures and in
      simulations of free myosin in solution, was found to be in a conformation
      stabilized with 1 - 2 internal salt bridges. The cardiomyopathy loop forms 2 - 3
      interprotein salt bridges with actin monomers upon binding, whereas its Arg405
      residue, the mutation site associated with the hypertrophic cardiomyopathy, forms
      a strong salt bridge with Glu605 in the neighboring helix away from actin in the
      actin-bound myosin. The myopathy loop of the R405Q mutant maintains a high degree
      of two-strand beta-sheet character when bound to actin with the corresponding
      salt bridges broken.

PMID- 16645963
TI  - Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators,
      and aging collide.

PMID- 16645964
TI  - Contribution of angiogenic genes to the complex genetic trait underlying Kawasaki
      disease.

PMID- 16645965
TI  - Methotrexate pharmacogenetics: the first step toward individualized therapy in
      rheumatoid arthritis.

PMID- 16645966
TI  - Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory
      drugs: high-risk subgroups and time course of risk.
AB  - OBJECTIVE: Controversy persists regarding the cardiovascular risks of treatment
      with selective cyclooxygenase 2 inhibitors (coxibs) and nonselective nonsteroidal
      antiinflammatory drugs (NSAIDs). This study was undertaken to examine, in a large
      group of new users of coxibs and NSAIDs, the rate of cardiovascular events, their
      time course, and whether baseline cardiovascular risk modified the rate ratios
      (RRs) for future events. METHODS: This cohort study included Medicare
      beneficiaries who enrolled in a state-run prescription drug plan that fully
      covered NSAIDs and coxibs without restriction. All study patients started use of
      a coxib or NSAID after January 1, 1999. The primary composite end point was a
      hospital admission for either myocardial infarction or ischemic stroke.
      Predefined exposure groups included the 3 coxibs available in the US during the
      study period (celecoxib, rofecoxib, and valdecoxib), as well as oral formulations
      of diclofenac, ibuprofen, naproxen, and a composite of all other NSAIDs. We
      compared the rate of cardiovascular events associated with each of these agents
      with that in a reference group of patients who did not use NSAIDs or coxibs, but
      started other medications unrelated to cardiovascular risk. Daily exposure to all
      study drugs was assessed based on filled prescription data. A Cox proportional
      hazards model stratified on calendar year that included other baseline
      cardiovascular risk factors constituted the primary analysis. RESULTS: We
      identified 74,838 users of NSAIDs or coxibs, and 23,532 comparable users of other
      drugs comprised the reference group. Adjusted models demonstrated a significant
      elevation in the event rate for rofecoxib (RR 1.15, 95% confidence interval [95%
      CI] 1.06-1.25) and a significant reduction in the rate for naproxen (RR 0.75, 95%
      CI 0.62-0.92). No other coxib or NSAID was associated with a significant increase
      or decrease in cardiovascular event rate. The increased rate associated with
      rofecoxib was seen in the first 60 days of use (adjusted RR 1.14, 95% CI 1.01
      1.29) and thereafter (adjusted RR 1.14, 95% CI 1.02-1.28). Kaplan-Meier event
      curves showed a similar pattern of risk (early and persistent separation of the
      event curves) among long-term rofecoxib users at low or high baseline
      cardiovascular risk. CONCLUSION: We found an increased cardiovascular event rate
      among users of rofecoxib, and a decreased rate with naproxen use. Other coxibs
      and NSAIDs did not appear to be associated with a difference in event rate
      compared with users of other drugs. The increase in rate associated with
      rofecoxib was seen within the first 60 days and persisted. There was no important
      modification of the event rate based on the patient's baseline cardiovascular
      risk.

PMID- 16645967
TI  - Combination treatment with methotrexate, cyclosporine, and intraarticular
      betamethasone compared with methotrexate and intraarticular betamethasone in
      early active rheumatoid arthritis: an investigator-initiated, multicenter,
      randomized, double-blind, parallel-group, placebo-controlled study.
AB  - OBJECTIVE: To investigate whether disease control can be achieved in early active
      rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular
      betamethasone, and whether the addition of cyclosporine to the regimen has any
      additional effect. METHODS: Patients (n = 160) were randomized to receive
      methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day
      (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At
      weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected
      into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if
      synovitis was present, the methotrexate dosage was increased stepwise up to 20
      mg/week, with a subsequent stepwise increase in the cyclosporine or placebo
      cyclosporine dosage up to 4 mg/kg. RESULTS: At 52 weeks, 20% improvement
      according to the American College of Rheumatology criteria (ACR20) was achieved
      in 85% of the combination therapy group versus 68% of the monotherapy group (P =
      0.02). The median individual overall ACR response (ACR-N) in the 2 groups was
      80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%),
      respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in
      35% of the combination therapy group and 28% of the monotherapy group.
      Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9
      (mean +/- SD) in the combination therapy and monotherapy groups, respectively.
      Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent,
      in the combination therapy group. CONCLUSION: Combined treatment with
      methotrexate and intraarticular glucocorticoid showed excellent disease control
      and stopped the progression of erosions in patients with early active RA, who had
      a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N
      responses, whereas the ACR50 and ACR70 responses, remission rates, and
      radiographic changes did not differ between the 2 study groups.

PMID- 16645968
TI  - Preliminary evidence for a structural benefit of the new bisphosphonate
      zoledronic acid in early rheumatoid arthritis.
AB  - OBJECTIVE: Bisphosphonates inhibit osteoclast activity, which is central to the
      development of bone damage in rheumatoid arthritis (RA). The aim of this study
      was to assess whether treatment with zoledronic acid, compared with placebo,
      could achieve a > or = 50% reduction in the development of new erosions on
      magnetic resonance imaging (MRI) in patients with early RA. METHODS: In this
      proof-of-concept study, 39 patients with early RA and clinical synovitis of the
      hand/wrist were randomized to receive infusions with either zoledronic acid (5
      mg) or placebo, administered at baseline and week 13. Patients in both groups
      received methotrexate (MTX) at a dosage of 7.5-20 mg/week. MRI and plain
      radiography were performed at baseline and week 26. RESULTS: At week 26, the mean
      +/- SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid
      group compared with the placebo group (0.9 +/- 1.63 versus 2.3 +/- 3.09; P =
      0.176). The mean +/- SD increase in the number of hand and wrist bones with
      erosions was 0.3 +/- 0.75 for zoledronic acid compared with 1.4 +/- 1.77 for
      placebo (P = 0.029). The proportion of patients in whom new MRI-visualized bone
      edema developed was smaller in the zoledronic acid group compared with the
      placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean
      change in the number of radiographic erosions of 0.1 compared with 0.5 for the
      placebo group (P = 0.677). The safety profile of zoledronic acid was similar to
      that of placebo. CONCLUSION: The results of this study suggest a structural
      benefit associated with zoledronic acid therapy in patients with RA, as
      demonstrated by consistent results in structural end points in favor of
      zoledronic acid plus MTX compared with MTX alone.

PMID- 16645969
TI  - The effect of therapeutic glucocorticoids on the adrenal response in a randomized
      controlled trial in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To measure the effect of low-dose systemic glucocorticoid treatment on
      the adrenal response to adrenocorticotropic hormone (ACTH) in patients with
      rheumatoid arthritis (RA). METHODS: Patients with RA who took part in a
      randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9
      mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with
      injection of ACTH (tetracosactide hexaacetate) at baseline and the day after
      completing the 3-month treatment program. Plasma cortisol measurements at
      baseline and 3 months were compared within and between the treatment groups.
      Individual patients were classified as normal responders to ACTH or as abnormal
      responders if changes were >2 SD below the pretreatment value in the entire group
      of study patients. RESULTS: Short tests with ACTH injection were performed on 139
      patients before beginning the study medication and on 134 patients after
      cessation of the medication. There were no changes in the placebo group. Mean
      plasma cortisol levels following treatment were reduced in all active treatment
      groups. In addition, mean values were significantly reduced for the 30-minute and
      60-minute responses to ACTH. The maximum reduction (35%) occurred in the
      prednisolone group at 60 minutes. Following treatment, 34% of patients taking
      budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the
      normal maximum cortisol response to ACTH. Four patients failed to achieve the
      normal percentage increase in cortisol levels, but only 1 patient failed to meet
      both criteria. CONCLUSION: Low doses of a glucocorticoid resulted in depression
      of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy.
      Although the responsiveness of the hypothalamic-pituitary-adrenal axis in
      individual patients generally remained within the normal range, these changes
      should be investigated further.

PMID- 16645970
TI  - Followup radiographic data on patients with rheumatoid arthritis who participated
      in a two-year trial of prednisone therapy or placebo.
AB  - OBJECTIVE: In a previous clinical trial of patients with early rheumatoid
      arthritis (RA), it was determined that patients who received 10 mg of prednisone
      per day for 2 years had less radiographic joint damage compared with those who
      received placebo. Our goal was to investigate whether this beneficial effect
      persisted after the end of the trial. METHODS: A blinded assessment of
      radiographic joint damage was performed approximately 3 years after the end of
      the original 2-year study. Twenty-four patients from the original prednisone
      group (60%) and 28 patients from the original placebo group (68%) participated in
      this followup study. At the end of the original trial, prednisone dosages were
      tapered down in the prednisone group and stopped, if possible. Patients from the
      original prednisone group took prednisone during 35% of the followup period
      (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients
      from the original placebo group started taking prednisone during followup.
      Radiographs of the hands and feet were scored according to the van der Heijde
      modification of the Sharp method. RESULTS: During 3 additional years of followup,
      radiographic scores showed significantly less progression in the original
      prednisone group than in the original placebo group. Radiographic damage in the
      original prednisone group did not show an accelerated rate of progression during
      the followup period. CONCLUSION: The inhibition of radiographic joint damage in
      patients with early active RA treated with 10 mg of prednisone per day for 2
      years seems to persist after the end of prednisone therapy.

PMID- 16645971
TI  - Guillain-Barre and Miller Fisher syndromes occurring with tumor necrosis factor
      alpha antagonist therapy.
AB  - OBJECTIVE: Diverse neurologic syndromes have been described in association with
      tumor necrosis factor alpha (TNFalpha) antagonist therapy for inflammatory
      arthritides and Crohn's disease. The objective of this study was to review the
      occurrence and clinical features of Guillain-Barre syndrome and its variant, the
      Miller Fisher syndrome, during TNFalpha antagonist therapy. METHODS: The
      postmarketing database of the US Food and Drug Administration (FDA) was searched,
      following our experience with a patient with rheumatoid arthritis in whom the
      Miller Fisher syndrome variant of the Guillain-Barre syndrome developed while he
      was receiving infliximab therapy. RESULTS: Our index patient had a neurologic
      illness defined initially by ataxia and dysarthria, which fluctuated in relation
      to each subsequent infliximab infusion and, after 6 months, culminated in
      areflexic flaccid quadriplegia. In addition, 15 patients in whom Guillain-Barre
      syndrome developed following TNFalpha antagonist therapy were identified from the
      FDA database. Guillain-Barre syndrome developed following infliximab therapy in 9
      patients, following etanercept therapy in 5 patients, and following adalimumab
      therapy in 1 patient. Among the 13 patients for whom followup data were
      available, 1 patient experienced no resolution, 9 patients had partial
      resolution, and 3 patients had complete resolution of Guillain-Barre syndrome
      following therapy. CONCLUSION: An association of Guillain-Barre syndrome with
      TNFalpha antagonist therapy is supported by the worsening of neurologic symptoms
      that occurred in our index patient following each infusion of infliximab, and by
      the temporal association of this syndrome with TNFalpha antagonist therapy in 15
      other patients. An acute or subacute demyelinating polyneuropathy should be
      considered a potential adverse effect of TNFalpha antagonist therapy.

PMID- 16645972
TI  - Leflunomide use and the risk of interstitial lung disease in rheumatoid
      arthritis.
AB  - OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients
      with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying
      antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we
      conducted a population-based epidemiologic study. METHODS: A cohort of 62,734
      patients with RA to whom a DMARD had been dispensed between September 1, 1998 and
      December 31, 2003 was formed using the PharMetrics claims database. A nested case
      control design was used, in which each case of serious ILD requiring
      hospitalization was matched to 100 controls according to age (calendar time) and
      equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of
      serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious
      ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of
      ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence
      interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and
      no history of ILD, the risk associated with leflunomide treatment was not
      elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining
      subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as
      likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The
      reports of ILD associated with leflunomide use are likely the result of
      channeling of high-risk patients to leflunomide treatment, particularly those
      with a history of methotrexate use or preexisting ILD. Patients with no history
      of ILD and no previous methotrexate use show no excess risk of developing ILD
      with leflunomide treatment.

PMID- 16645973
TI  - Radiographic joint space width in the fingers of patients with rheumatoid
      arthritis of less than one year's duration.
AB  - OBJECTIVE: To determine the radiographic joint space width (JSW) in undamaged
      metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients
      with early rheumatoid arthritis (RA) and to identify important clinical
      determinants of JSW. METHODS: Radiographs of patients with RA of <1 year's
      duration, from an early arthritis cohort at a tertiary care rheumatology clinic,
      were obtained. JSW was analyzed by joint, finger, age, sex, height, and a number
      of other clinically relevant variables. Multivariate analysis was also performed,
      to account for possible confounding between variables. RESULTS: Thirty-eight
      patients were included in the study. We found that JSW was greater in the MCP
      joint than the PIP joint (P < 0.0001). JSW was significantly greater in men (P <
      0.0001) and increased with increasing height (P < 0.003), but was not associated
      with age (P < 0.21). In multivariate analyses, sex was shown to be the most
      important predictor of JSW. CONCLUSION: In patients with early RA, MCP and PIP
      JSW is significantly associated with sex and height. In studies of RA in which
      JSW measurements are included as an outcome, these differences may need to be
      accounted for in the analysis.

PMID- 16645974
TI  - Performance of an automated computer-based scoring method to assess joint space
      narrowing in rheumatoid arthritis: a longitudinal study.
AB  - OBJECTIVE: To compare the diagnostic performance of a computer-based method for
      measuring joint space width with the Sharp joint space narrowing (JSN) scoring
      method in patients with rheumatoid arthritis (RA). METHODS: A random sample of
      patients with early RA, for whom sequential hand radiographs and Sharp scores
      were available, was selected from the National Data Bank for Rheumatic Diseases.
      Hand joint space width was measured using an automated, computer-based method in
      random order and with blinding for clinical information. We constructed a
      receiver operating characteristic curve and compared the diagnostic performance
      of the computer-based and Sharp methods based on the areas under the curve.
      RESULTS: One hundred twenty-nine patients with early RA who underwent serial
      radiography were included. Changes in the computer-based and Sharp methods were
      highly correlated (r = 0.75, P < 0.001). The computer-based method was
      significantly more discriminant than the Sharp JSN subscale. The area under the
      curve of the computer-based method was 0.96 (95% confidence interval [95% CI]
      0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P =
      0.024). At the most discriminant cutoff, specificity of the computer-based method
      was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was
      87.6% for the computer-based method compared with 82.2% for Sharp subscale (P =
      0.19). The signal-to-noise ratio for the computer-based method was 83% compared
      with 70% for the Sharp subscale (P = 0.013). CONCLUSION: The computer-based
      method for measuring joint space width is more discriminant than the
      semiquantitative Sharp JSN subscale.

PMID- 16645975
TI  - Capillary electrophoresis-mass spectrometry of a new cross-linker with acrylic
      functionality.
AB  - Analytical characterization of dimethacrylate-tyrosine-lysine-tyrosine (DMTLT, a
      new biodegradable acrylic cross-linker synthesized at our laboratory) is carried
      out using CE-MS. DMTLT is a pseudopeptide composed by tyrosine-lysine-tyrosine
      amino acids linked through urea bonds with two methacrylic groups, one at each
      end of the molecule, making this compound an excellent cross-linker for
      polymerization reactions and for obtaining new biodegradable materials. A new CE
      MS method is developed for the characterization of DMTLT and its products of
      degradation after basic hydrolysis. In order to carry out an exhaustive
      examination of such degradation products methods based on CE coupled to IT and
      TOF-MS are employed. Based on CE-IT-MS results and the elemental composition of
      the degradation products obtained by CE-TOF-MS, conclusions on the mechanism and
      kinetic of hydrolysis of DMTLT are obtained confirming both the usefulness of CE
      MS to characterize new biomaterials and the applicability of DMTLT for preparing
      new biodegradable polymers. These results are corroborated through the CE-MS
      detection of the identified products of degradation in a dimethyl acrylamide
      polymer cross-linked with DMTLT.

PMID- 16645976
TI  - Analysis of arsenic compounds by capillary electrophoresis using indirect UV and
      mass spectrometric detections.
AB  - CE with indirect UV and mass-spectrometric detection was used for the
      simultaneous determination of arsenic acid (As(V)), arsenous acid (As(III)),
      monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide
      (TMAO), tetramethylarsonium ion (TMA(+)), arsenobetaine (AB), and arsenocholine
      (AC). In the CE-indirect UV analysis, a baseline separation of arsenic species
      was successfully achieved by using a basic background solution (BGS) for anions
      and an acidic BGS for cations, respectively. The LOD values in CE-indirect UV for
      the individual analytes were 7.8, 12.5, 7.8, 12.5, 62.5, 125, 250, and 62.5 ppm,
      respectively. To achieve sensitive and selective analysis, CE coupled with ESI-MS
      was applied to the determination of arsenic compounds. The organic arsenic
      species were successfully separated with a higher sensitivity by CE-MS using the
      acidic BGS. The LODs in CE-MS for MMA, DMA, TMAO, TMA(+), AB, and AC were 1.0,
      0.1, 0.01, 0.1, 0.01, and 0.01 ppm, respectively. In contrast, the analysis of
      inorganic arsenic species (As(V) and As(III)) resulted in a lower detectability
      in CE-MS compared to that obtained with the CE-indirect UV analysis. However, the
      speciation of eight arsenics by CE-MS was successfully achieved in a single run
      by switching the ESI polarity during MS detection.

PMID- 16645977
TI  - Analysis of polymerase chain reaction amplifications through phosphate detection
      using an enzyme-based microbiosensor in a microfluidic device.
AB  - An electrochemical method was developed for analyzing PCR amplification through
      the detection of inorganic phosphates (Pi). This method coupled a microchip to a
      nanoparticle comprising poly-5,2'-5',2''-terthiophene-3'-carboxylic acid (poly
      TTCA)/pyruvate oxidase (PyO) modified microbiosensor. It detects Pi produced from
      the pyrophosphate (PPi), which is released as a byproduct of PCR. After
      completion of PCR, PPi is hydrolyzed to Pi by inorganic pyrophosphatase. On the
      microbiosensor surface, pyruvate was converted to H2O2 by PyO in the presence of
      Pi and oxygen, and subsequently, the anodic current of enzymatically generated
      H2O2 was detected at +0.5 V versus Ag/AgCl. The CE-EC analysis was completed
      within 2 min in a coated channel with 75.0 mm separation length at the field
      strength of -200 V/cm. Excellent operation stability of poly-TTCA/PyO was
      observed for a long period of analysis. The reproducibility of the analysis
      yielded an RSD of 3.4% (n = 22) for the peak areas and 1.8% (n = 22) for the
      migration times. The sensitivity of the analysis was 0.59 +/- 0.01 nA/cycle with
      a regression coefficient of 0.971.

PMID- 16645978
TI  - Sample pretreatment on a microchip with an integrated electrospray emitter.
AB  - This study presents a microbead-packed PDMS microchip with an integrated
      electrospray emitter for sample pretreatment prior to sheathless ESI-MS. We prove
      the concept of analytical functions integrated onto a cm-sized area of a single
      bulk material. The microchip consists of two PDMS substrates replicated from SU-8
      fabricated silicon wafer masters, bonded together after oxidation by corona
      discharge treatment. The channel within the microchip contains a grid structure
      that was used to trap 5 microm hypercross-linked polystyrene beads. The beads
      acted as a medium for sample desalting and enrichment. Electrical contact for the
      sheathless ESI process was achieved by coating the integrated emitter with
      conductive graphite powder after applying a thin layer of PDMS as glue. The
      coating as well as the bond of the PDMS structures showed excellent durability. A
      continuous spray was obtained from the microchip for over 800 h in a long-term
      electrospray stability experiment. Desalting and enrichment of neuropeptides from
      a physiological salt solution was successful by loading the sample onto the
      packed beads, followed by a washing and an eluting step. The results were
      obtained and evaluated using a TOF MS. An LOD of approximately 20 fmol (loaded
      onto the beads) for angiotensin II was obtained from a sample of neuropeptides
      dissolved in physiological salt solution.

PMID- 16645979
TI  - Sheathless capillary electrophoresis-mass spectrometry using a pulsed
      electrospray ionization source.
AB  - A sheathless interface has been developed for coupling CE with electrospray IT
      mass spectrometer. This interface utilized a pulsed ESI source. The use of a
      pulsed electrospray source allows the use of a sprayer with larger orifice, and
      thus alleviates the problem of column clogging during conductive coating and CE
      analysis. A pulsed ESI source operated at 20 Hz and 20% duty cycle was found to
      produce the optimal signals. For better signals, the maximum ion injection time
      in the IT mass spectrometer has to be set to a value close to the actual spraying
      time (10 ms). Using a sprayer with 50 microm od, more stable and enhanced signals
      were obtained in comparison with continuous CE-ESI-MS under the same flow rate
      (150 nL/min). The utility of this design is demonstrated with the analysis of
      synthetic drugs by CE-MS.

PMID- 16645980
TI  - Biomarker discovery by CE-MS enables sequence analysis via MS/MS with platform
      independent separation.
AB  - CE-MS is a successful proteomic platform for the definition of biomarkers in
      different body fluids. Besides the biomarker defining experimental parameters, CE
      migration time and molecular weight, especially biomarker's sequence identity is
      an indispensable cornerstone for deeper insights into the pathophysiological
      pathways of diseases or for made-to-measure therapeutic drug design. Therefore,
      this report presents a detailed discussion of different peptide sequencing
      platforms consisting of high performance separation method either coupled on-line
      or off-line to different MS/MS devices, such as MALDI-TOF-TOF, ESI-IT, ESI-QTOF
      and Fourier transform ion cyclotron resonance, for sequencing indicative
      peptides. This comparison demonstrates the unique feature of CE-MS technology to
      serve as a reliable basis for the assignment of peptide sequence data obtained
      using different separation MS/MS methods to the biomarker defining parameters, CE
      migration time and molecular weight. Discovery of potential biomarkers by CE-MS
      enables sequence analysis via MS/MS with platform-independent sample separation.
      This is due to the fact that the number of basic and neutral polar amino acids of
      biomarkers sequences distinctly correlates with their CE-MS migration
      time/molecular weight coordinates. This uniqueness facilitates the independent
      entry of different sequencing platforms for peptide sequencing of CE-MS-defined
      biomarkers from highly complex mixtures.

PMID- 16645981
TI  - Simultaneous enantioseparation and sensitive detection of eight beta-blockers
      using capillary electrochromatography-electrospray ionization-mass spectrometry.
AB  - The feasibility of using vancomycin chiral stationary phase (CSP) and polar
      organic eluent is investigated for simultaneous enantioseparation of eight beta
      blockers using CEC coupled to ESI mass spectrometric detection (ESI-MS). The
      internally tapered capillaries were utilized to pack CEC-MS columns. As compared
      to externally tapered columns, the use of internally tapered columns demonstrated
      enhanced stability, durability, and reproducibility. A mixture containing
      methanol/ACN/acetic acid/triethylamine at 70:30:1.6:0.2 v/v/v/v was considered as
      optimum mobile phase since it provided a good compromise between resolution and
      analysis time. As expected, sheath liquid and ESI-MS parameters mainly influenced
      the detection sensitivity. Interestingly, structural information of beta-blockers
      was available by varying the MS fragmentor voltage using in-house CID in the scan
      mode. In order to maximize the chiral/achiral resolution, various column-coupling
      approaches using teicoplanin as complementary CSP to vancomycin were tested.
      Several changes in the elution order of beta-blockers were observed using
      multimodal CSPs with some improvement in chiral or achiral resolution. The
      quantitative aspects of the CEC-MS method were demonstrated using R- and S
      talinolol as internal standards. The calibration curves of beta-blockers showed
      good linearity in the range of 3-600 microM. The enantiomer of beta-blockers at a
      concentration of 30 nM was detectable. Furthermore, both 0.1 and 1% of the S
      enantiomer could be precisely quantified in the presence of 99.9 and 99% of the R
      isomer of beta-blocker.

PMID- 16645982
TI  - Progress in capillary electrophoresis coupled to matrix-assisted laser
      desorption/ionization - time of flight mass spectrometry.
AB  - In this review the most important techniques developed to hyphenate CE to MALDI
      TOF-MS are summarized. The principles of the different interfaces and ways to
      solve the hyphenation problem are explained and discussed in detail. The most
      important applications especially in the proteomic field are reviewed, and the
      advantages of CE-MALDI-TOF-MS for the analysis of these compounds compared to
      other techniques such as ESI-MS are exhaustingly discussed from a critical point
      of view. CE coupled to MALDI-TOF-MS has started to overpass traditionally used CE
      coupling techniques, especially CE-ESI-MS, offering the possibility to analyze
      samples of interest even weeks after CE analysis and using multiplexing systems
      for high-sample throughput.

PMID- 16645983
TI  - Selective binding and enrichment for low-molecular weight biomarker molecules in
      human plasma after exposure to nanoporous silica particles.
AB  - The present manuscript describes a biomarker capturing strategy based on
      nanoporous silica particles. The method is shown to enrich the yield of species
      in the low-molecular weight proteome (LMWP), allowing detection of small peptides
      in the low-nanomolar range. Plasma samples were exposed to the silica particles,
      and the captured molecular species were profiled using MALDI-TOF. Mass spectra of
      the silica-treated human plasma samples showed a significant enrichment in MALDI
      TOF protein profiles in the LMWP. Preliminary results indicated good level of
      reproducibility in plasma profiles with CVs on peak heights ranging from 6.3 to
      14.7%. The MALDI-TOF signature changed significantly when the characteristics of
      the nanoporous silica were altered. The facile sample pretreatment before MS
      analysis, coupled to the potential for tailoring the surface properties of silica
      supports, hold promise for improving the recovery of low-abundance serum
      biomarkers.

PMID- 16645984
TI  - Suppression of human selenium-binding protein 1 is a late event in colorectal
      carcinogenesis and is associated with poor survival.
AB  - The purpose of this study was to analyze altered protein expression in cancer
      tissues and determine its relationship to prognosis in colorectal carcinomas. We
      performed proteomic expression analysis on 14 colorectal carcinomas and matched
      nontumorous colonic mucosa by 2-DE and MALDI-TOF-MS. Comparative analysis of the
      respective spot patterns on 2-DE showed 14 spots that were markedly changed in
      the colorectal carcinomas. Among them, selenium-binding protein 1 (SELENBP1) was
      markedly decreased in 12 (85%) carcinomas. The reduced expression of SELENBP1 was
      further supported by Western blot analysis and immunohistochemistry. Suppression
      of SELENBP1 was further analyzed in another eight-paired adenomas and carcinomas
      from the same patients using Western blot analysis and immunohistochemistry, and
      revealed that one adenoma and seven carcinomas exhibited markedly reduced
      SELENBP1 expression. Patients with low levels of SELENBP1 expression had
      significantly lower overall survival rates (72 vs. 85%, p = 0.021) among the 240
      stages II and III colorectal carcinomas by using tissue microarray analysis. Our
      findings indicate that suppression of SELENBP1 is a frequent and late event in
      colorectal carcinogenesis, and may contribute to the rapid progression of
      colorectal carcinoma.

PMID- 16645985
TI  - Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared
      from the group B strain NZ98/254.
AB  - In the absence of a suitable carbohydrate-based vaccine, outer membrane vesicle
      (OMV) vaccines have been used to disrupt outbreaks of serogroup B meningococcal
      disease for more than 20 years. Proteomic technology provides physical methods
      with the potential to assess the composition and consistency of these complex
      vaccines. 2-DE, combined with MS, were used to generate a proteome map of an OMV
      vaccine, developed to disrupt a long-running outbreak of group B disease in New
      Zealand. Seventy four spots from the protein map were identified including the
      outer membrane protein (OMP) antigens: PorA, PorB, RmpM and OpcA. Protein
      identification indicates that, in addition to OMPs, OMV vaccines contain
      periplasmic, membrane-associated and cytoplasmic proteins. 2-D-DIGE technology
      highlighted differences between preclinical development batches of vaccines from
      two different manufacturers.

PMID- 16645986
TI  - Depletion efficiency and recovery of trace markers from a multiparameter
      immunodepletion column.
AB  - The selective removal of high-abundance proteins is considered to be an important
      prerequisite for a sensitive proteome analysis in plasma. In this study, we
      examined the "multiaffinity removal system", an immunoaffinity depletion column
      targeted against six plasma proteins. As determined by sandwich ELISA, the
      depletion rate for each target protein is >99% over 200 cycles of regeneration.
      Our data give evidence that two column antibodies are slowly inactivated during
      the repeated use of the column; however, the individual depletion rate meets the
      specification of the manufacturer. To estimate a potential loss of analytes after
      the immunodepletion, we performed spiking/recovery experiments with a selection
      of tumor markers at concentrations in the lower to medium ng/mL range. The
      average recovery of 9 out of 11 markers is 78%. A significant proportion of two
      other markers binds to the column. Based on the average marker recovery and a
      depletion of ;85% of the total protein we estimate a five-fold enrichment of a
      potential biomarker by the use of this depletion column. We conclude that the
      selective depletion of plasma proteins by immunoaffinity chromatography is a
      valid strategy for the enrichment of potential biomarkers sought by proteomics
      methodologies.

PMID- 16645987
TI  - Development of a preliminary index that predicts adverse events after total knee
      replacement.
AB  - OBJECTIVE: We undertook this study to assess the relationships between hospital
      characteristics, volume of procedures, and perioperative outcomes after total
      knee replacement (TKR), and to use this information to construct a simple
      predictive index for perioperative outcomes that incorporates hospital- and
      patient-level characteristics. METHODS: We studied Medicare beneficiaries who
      underwent TKR in 4 US states in 2000. Orthopedic surgery administrators from
      hospitals caring for patients in this sample were surveyed about a range of
      hospital characteristics. The relationships between these hospital
      characteristics, patient variables, and 90-day postoperative adverse events
      (including death, pulmonary embolus, pneumonia, deep wound infection, and acute
      myocardial infarction) were assessed using generalized estimating equations
      adjusting for hospital volume. These relationships were assessed in low- and high
      risk patient groups. Variables from the final multivariate model were used to
      create an index that was tested against 90-day adverse event rates. RESULTS:
      Three hundred twenty-seven (3.6%) of the patients undergoing TKR in our sample
      experienced an adverse event. In the final multivariate regression models,
      variables that predicted adverse perioperative events included low hospital
      volume (fewer than 23 TKRs in the Medicare population per year), absence of a
      preoperative teaching program, fewer TKRs conducted in a dedicated orthopedic
      surgery operating room, patient age >70 years, male sex, and at least 1 comorbid
      condition. The effect of volume on perioperative adverse events was evident both
      in patients with few risk factors and in patients with several risk factors. An
      index including the 6 patient and hospital variables discriminated well, with
      adverse events occurring in 2.0% (95% confidence interval [95% CI] 1.4-2.7%) of
      patients in the lowest risk category and in 7.4% (95% CI 4.5-12.3%) of patients
      in the highest risk category (P for trend < 0.001). The index predicted adverse
      event rates both in hospitals with a low volume of TKRs and in those with a high
      volume of TKRs. CONCLUSION: Characteristics of hospital care, procedure volume,
      and patient-level factors are all associated with perioperative outcomes of TKR.
      A preliminary index combining hospital characteristics and volume is moderately
      predictive of adverse perioperative outcomes. The index is predictive of outcome
      in low- and high-volume hospitals.

PMID- 16645988
TI  - Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91
      pathway in systemic lupus erythematosus.
AB  - OBJECTIVE: A deficiency in a subcomponent of C1q can result in increased
      susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE).
      The monocyte endocytic receptor CD91 is implicated in the endocytosis of
      apoptotic neutrophils via interactions with C1q and calreticulin. In this
      clinical study, we studied the binding of C1q to leukocytes and determined
      whether C1q bound specifically to calreticulin and CD91 on cells undergoing
      apoptosis in SLE. METHODS: Proximal antibody phage display, calreticulin
      transfected cells, and immunocytochemical and confocal techniques were used in a
      comprehensive analysis of direct binding of C1q to apoptotic neutrophils that
      were obtained from healthy individuals and from patients with SLE. In addition,
      apoptotic cellular systems were assessed in vitro. RESULTS: C1q appeared to
      colocalize to apoptotic blebs on the surface of leukocytes in association with
      both calreticulin and CD91, as determined by phage display and transfected cell
      studies. However, C1q did not bind to apoptotic cells isolated from SLE patients,
      despite the positivity of the cells for both calreticulin and CD91. Surface
      expression of calreticulin decreased on neutrophils as they aged, but increased
      on monocytes. In an apoptotic phagocytic assay, the addition of C1q and
      calreticulin significantly enhanced the phagocytosis of apoptotic cell debris by
      monocyte-derived cells. CONCLUSION: These observations indicate that neutrophils
      from SLE patients have a reduced ability to be recognized and removed by the
      C1q/calreticulin/CD91-mediated apoptotic pathway, despite the presence of main
      apoptotic recognition partners. This suggests that an additional component, as
      yet unidentified, acts as a C1q binding partner on apoptotic cells, and this
      component may be lacking in cells isolated from SLE patients.

PMID- 16645989
TI  - "Endogenous adjuvant" activity of the RNA components of lupus autoantigens Sm/RNP
      and Ro 60.
AB  - OBJECTIVE: Most lupus patients produce autoantibodies against small
      ribonucleoproteins such as Sm/RNP and Ro 60 (containing U1 and Y1-Y5 RNAs,
      respectively). We undertook this study to investigate whether the RNA components
      of these antigens, which contain extensive tracts of single- and double-stranded
      RNA, signatures of viral infection, activate innate immunity. METHODS: U1 and Y
      RNAs were affinity purified from K562 cells. Murine bone marrow-derived dendritic
      cells (DCs), human HEK 293 cells, and murine RAW264.7 cells were stimulated with
      U1 RNA and other known Toll-like receptor (TLR) ligands. Expression of the
      interferon (IFN)-inducible gene Mx1 and other genes was quantified using real
      time polymerase chain reaction, and cytokine production was measured by enzyme
      linked immunosorbent assay. DC maturation was assessed using flow cytometry.
      RESULTS: Purified U1 and Y1-Y5 RNAs and synthetic stem-loop II of U1 RNA
      stimulated type I IFN (IFN-I) production by cell lines and murine bone marrow
      derived DCs and promoted DC maturation (CD86 expression). U1 RNA-stimulated, but
      not TLR-3 ligand-stimulated, IFN-I was blocked by bafilomycin A1, indicating that
      immunostimulation by U1 RNA requires endosomal acidification. Myeloid
      differentiation factor 88-deficient cells responded poorly to U1 RNA, suggesting
      that an endosomal TLR, probably TLR-7, mediates the stimulatory effects of U1
      RNA. U1 RNA-induced IFN-I and interleukin-6 production also were protein kinase R
      (PKR) dependent (abrogated by 2-aminopurine and greatly reduced in PKR-/- cells).
      CONCLUSION: We conclude that the RNA components of the Ro 60 (Y1-Y5 RNA) and
      Sm/RNP (U1 RNA) small ribonucleoproteins act as endogenous adjuvants that could
      play a role in the pathogenesis of autoimmunity by stimulating DC maturation and
      IFN-I production.

PMID- 16645990
TI  - Antibodies to ribosomal P proteins: a potential serologic marker for lupus
      membranous glomerulonephritis.
AB  - OBJECTIVE: To evaluate the relevance of antibodies to ribosomal P proteins (anti
      P antibodies) in discriminating histopathologic patterns of lupus nephritis.
      METHODS: The study group comprised 81 consecutive patients with systemic lupus
      erythematosus who underwent renal biopsy and for whom frozen serum was available
      at the time of biopsy. All biopsy specimens were reviewed in a blinded manner,
      according to the 2004 criteria of the International Society of Nephrology and the
      Renal Pathology Society. Anti-P antibodies were detected by enzyme-linked
      immunosorbent assay (ELISA)/immunoblot analysis, and anti-double-stranded DNA
      (anti-dsDNA) was detected by indirect immunofluorescence/ELISA. RESULTS: Anti-P
      antibodies were detected in 18 patients (22%). The demographic and clinical
      features of patients with and those without anti-P antibodies were similar.
      Remarkably, analyses of biopsy specimens revealed that the frequency of anti-P
      antibodies in patients with class V lupus nephritis was higher than the frequency
      among patients with other classes of renal disease (72% versus 28%; P = 0.005).
      Accordingly, anti-P antibody-positive patients had a higher mean (+/-SD)
      proteinuria level compared with anti-P antibody-negative patients (6.4 +/- 4.8
      versus 4.7 +/- 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7
      patients who had both isolated anti-P antibodies and class V lupus nephritis. In
      contrast, anti-dsDNA was associated with proliferative-class lupus nephritis (P =
      0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients
      with isolated anti-P antibodies had class V lupus nephritis, and, more
      importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern.
      Conversely, a tendency toward the predominance of class V lupus nephritis (67%)
      with concomitant proliferative lesions was observed when anti-P antibody was
      associated with anti-dsDNA. CONCLUSION: Our data introduce anti-P antibody as a
      novel serologic marker for membranous lupus nephritis and support the notion that
      the presence of isolated anti-P antibodies may discriminate patients with pure
      class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA
      antibodies suggests class V disease with concomitant proliferative lesions.

PMID- 16645991
TI  - Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem
      mass spectra of poly(butylene adipate).
AB  - Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem
      mass spectrometry (MALDI-TOF/TOF-MS/MS) was employed to analyze four
      poly(butylene adipate) (PBAd) oligomers and to investigate their fragmentation
      pathways as a continuation of our work on the MALDI-TOF/TOF-MS/MS study of
      synthetic polymers. MALDI-TOF/TOF-MS/MS analysis was performed on oligomers
      terminated by carboxyl and hydroxyl groups, methyl adipate and hydroxyl groups,
      dihydroxyl groups, and dicarboxyl groups. The sodium adducts of these oligomers
      were selected as precursor ions. Different end groups do not influence the
      fragmentation of sodiated polyester oligomers and similar series of product ions
      were observed in all the MALDI-TOF/TOF-MS/MS spectra. According to the structures
      of the most abundant product ions identified in the present work, three
      fragmentation pathways have been proposed to occur most frequently in PBAd: beta
      hydrogen-transfer rearrangement, leading to the selective cleavage of the --O-
      CH(2)-- bonds; --CH(2)--CH(2)-- (beta--beta) bond cleavage in the adipate moiety;
      and ester bond scission.

PMID- 16645992
TI  - Lupus-like disease and high interferon levels corresponding to trisomy of the
      type I interferon cluster on chromosome 9p.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with type I
      interferons (IFNs) and can be induced by IFNalpha treatment. This study looked
      for evidence of autoimmunity in a pedigree consisting of 4 family members with a
      balanced translocation 9;21 and 2 members with an unbalanced translocation
      resulting in trisomy of the short (p) arm and part of the long (q) arm of
      chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster.
      METHODS: Subjects were evaluated clinically and serologically for autoimmune
      disease. Expression levels of IFNalpha4, IFNbeta, the type I IFN-inducible gene
      Mx1, the type I IFN receptor, interleukin-6, and tumor necrosis factor alpha were
      determined by real-time polymerase chain reaction. Circulating plasmacytoid
      dendritic cells, the main IFN-producing cells, were quantified by flow cytometry.
      RESULTS: Both subjects with trisomy of chromosome 9p had a lupus-like syndrome
      with joint manifestations and antinuclear antibodies: one had anti-RNP and
      antiphospholipid autoantibodies, and the other had anti-Ro 60. The 3 family
      members with a balanced translocation 9;21 had no clinical or serologic evidence
      of autoimmunity, similar to that in relatives who were unaffected by the
      chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of
      IFNalpha/beta (comparable with those found in patients with SLE), increased
      signaling through the IFN receptor (as indicated by high Mx1 expression), and low
      levels of circulating plasmacytoid dendritic cells (as observed in patients with
      SLE) were evident. These abnormalities were not seen in individuals with a
      balanced translocation. CONCLUSION: Trisomy of the type I IFN cluster of
      chromosome 9p was associated with lupus-like autoimmunity and increased
      IFNalpha/beta and IFN receptor signaling. The data support the idea that abnormal
      regulation of type I IFN production is involved in the pathogenesis of SLE.

PMID- 16645993
TI  - Nuclear Ptdlns(3,4,5)P3 signaling: an ongoing story.
AB  - Phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P(3)) is linked to a
      variety of cellular functions, such as growth, cell survival, and
      differentiation. Ptdlns(3,4,5)P(3) is primarily synthesized by class I
      phosphoinositide 3-kinases and its hydrolysis by two 3-phosphoinositide 3
      phosphatases, PTEN and SHIP proteins, leads to the production of two other second
      messengers, Ptdlns(4,5)P(2) and Ptdlns(3,4)P(2), respectively. Evidence
      accumulated over the last years strongly suggest that Ptdlns(3,4,5)P(3) is an
      important component of signaling pathway operating within the nucleus. Moreover,
      recent advances indicated that nuclear translocation of cell surface receptors
      could activate nuclear phosphoinositide 3-kinase suggesting a new mode of signal
      transduction. The aim of this review is intended to summarize the state of our
      knowledge on nuclear Ptdlns(3,4,5)P(3) and its metabolizing enzymes, and to
      highlight the emerging roles for intranuclear Ptdlns(3,4,5)P(3).

PMID- 16645994
TI  - Systemic lupus erythematosus in a multiethnic US cohort. XXXIII. Clinical
      [corrected] features, course, and outcome in patients with late-onset disease.
AB  - OBJECTIVE: To examine the clinical differences and the type and extent of organ
      damage in late- versus early-onset systemic lupus erythematosus (SLE). METHODS: A
      nested case-control study was performed in the context of LUMINA (LUpus in
      MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort.
      Patients who developed SLE at or after the age of 50 years were considered cases.
      Two controls (patients who developed SLE at age < or = 49 years) per case,
      matched for sex and disease duration, were randomly chosen. Selected baseline
      socioeconomic/demographic, behavioral, and psychological features, self-reported
      quality of life, and cumulative clinical data (clinical manifestations,
      laboratory data, disease activity, damage, and mortality) were compared between
      cases and controls. Multivariable analyses with late-onset lupus, damage accrual,
      and mortality as dependent variables were then performed. RESULTS: Two hundred
      seventeen patients were studied. Of them, 73 were cases. Cases were more likely
      to have neurologic involvement, arterial thrombotic events, osteoporosis, and
      hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less
      frequent. Disease activity at baseline was lower among cases. Cases also
      exhibited more cardiovascular and ocular damage. Late-onset lupus was an
      independent predictor of damage accrual (t-test = 2.23, P = 0.028), any damage at
      last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98-141.56)
      (P < 0.001), and mortality (OR 10.74, 95% CI 3.07-37.56) (P < 0.001). CONCLUSION:
      Patients with late-onset lupus exhibit distinct clinical features. Although
      disease activity tends to be lower in these patients, they tend to accrue more
      damage and experience higher mortality than patients with early-onset lupus.
      These findings probably reflect the contribution exerted by other comorbid
      conditions in the overall impact of lupus in these patients.

PMID- 16645995
TI  - Vascular endothelial growth factor gene haplotypes in Kawasaki disease.
AB  - OBJECTIVE: To investigate whether common genetic variants in the vascular
      endothelial growth factor (VEGF) gene are associated with Kawasaki disease (KD)
      and the subsequent development of coronary artery lesions. METHODS: Common
      genetic variants in the VEGF gene were analyzed in an association study in a
      Dutch cohort of 170 KD patients and 300 healthy Dutch Caucasian controls.
      Genotyping was done with 5'-nuclease TaqMan assays and 3'-hybridization-triggered
      fluorescence minor groove binder Eclipse assays. RESULTS: An association with
      susceptibility to KD was observed with 2 of the 6 single-nucleotide polymorphisms
      analyzed in VEGF: -2594 A>C (rs699947) and the 236 bp 3' of STP C>T (rs3025039).
      Also for an 18-bp deletion in the promoter of VEGF a significant difference in
      the genotype and allele frequencies was observed between the KD patients and the
      controls. The haplotype CGCC (based on rs699947, rs2010963, rs25648, and
      rs3025039) was significantly associated with the development of KD (hap score
      3.8; P = 0.0002). VEGF plasma levels were significantly higher in patients with
      the early phase of KD than in the healthy controls, and there was a trend toward
      higher VEGF plasma levels in KD patients with the -2594 CC and 236 bp 3' of STP
      CC genotypes. CONCLUSION: Our results suggest that polymorphisms of the VEGF gene
      may play a role in the pathogenesis of KD.

PMID- 16645996
TI  - A Bayesian dynamic model for influenza surveillance.
AB  - The severe acute respiratory syndrome (SARS) epidemic, the growing fear of an
      influenza pandemic and the recent shortage of flu vaccine highlight the need for
      surveillance systems able to provide early, quantitative predictions of epidemic
      events. We use dynamic Bayesian networks to discover the interplay among four
      data sources that are monitored for influenza surveillance. By integrating these
      different data sources into a dynamic model, we identify in children and infants
      presenting to the pediatric emergency department with respiratory syndromes an
      early indicator of impending influenza morbidity and mortality. Our findings show
      the importance of modelling the complex dynamics of data collected for influenza
      surveillance, and suggest that dynamic Bayesian networks could be suitable
      modelling tools for developing epidemic surveillance systems.

PMID- 16645997
TI  - Fast gas chromatography-negative-ion chemical ionization mass spectrometry with
      microscale volume sample preparation for the determination of benzodiazepines and
      alpha-hydroxy metabolites, zaleplon and zopiclone in whole blood.
AB  - Fast gas chromatography/negative-ion chemical ionization mass spectrometric
      (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is
      presented for the simultaneous determination of benzodiazepines and alpha-hydroxy
      metabolites, zaleplon and zopiclone in whole blood. The compounds were extracted
      from 100 microl of whole blood by simultaneous multitube, microscale liquid
      liquid extraction (LLE) and derivatized by N-methyl-N-(tert
      butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time
      consuming concentration stage. In the analytical separation, various parameters
      of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a
      high carrier gas velocity, a small film thickness of the analytical column, fast
      MS data acquisition, fast temperature ramping, and high initial and final
      temperatures of GC column. Sensitive identification, screening and quantitation
      of 18 compounds of interest were achieved in chromatographic separation in only
      4.40 min. Accurate and reproducible results were obtained by using five different
      and carefully selected deuterated analogues on the basis of the chemical
      properties of the target analytes. Nevertheless, for alpha-OH-midazolam, and for
      bromazepam and flunitrazepam at low concentrations, the results can be considered
      only semiquantitative on the basis of the validation data. The extraction
      efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from
      1 to 100 ng ml(-1). Rapid sample preparation and fast chromatographic separation
      allowed cost-efficient, reliable and high sample-throughput analyses with a low
      amount of manual work. The method was fully validated and accredited according to
      EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and
      quantitative determination of benzodiazepines, zaleplon and zopiclone, e.g. in
      clinical and forensic toxicology.

PMID- 16645998
TI  - Predictors of disease course and remission in systemic juvenile idiopathic
      arthritis: significance of early clinical and laboratory features.
AB  - OBJECTIVE: To determine whether the disease course in systemic juvenile
      idiopathic arthritis (JIA) can be characterized as monophasic, polycyclic, or
      persistent, and to determine whether early clinical and laboratory
      characteristics can be used to predict the disease course and time to remission.
      METHODS: Forty-five children with systemic JIA diagnosed between 1996 and 2000
      were followed up with a standardized data collection protocol, including data on
      clinical and laboratory features (mean followup 4.9 years). Disease was
      considered inactive if the clinical and laboratory features were normal. Three
      definitions of remission were applied to classify disease course. Predictors of
      disease course were evaluated using multiple logistic regression. Predictors of
      time to remission were evaluated using Cox proportional hazards regression.
      RESULTS: When applying a definition of remission requiring inactive disease while
      not receiving any medications for a period of 3 months, 42.2%, 6.7%, and 51.1% of
      the patients were classified as having monophasic, polycyclic, and persistent
      disease, respectively. Fever and active arthritis at 3 months (R2 = 0.42, area
      under the receiver operating characteristics curve [AUC] = 0.76) and an
      erythrocyte sedimentation rate (ESR) >26 mm/hour and corticosteroid use at 6
      months (R2 = 0.49, AUC = 0.92) were predictive of a nonmonophasic course. Absence
      of active arthritis, an ESR of <26 mm/hour, and no requirement for corticosteroid
      therapy at 3 and 6 months were predictors of an earlier time to remission.
      CONCLUSION: The disease course in systemic JIA can be characterized as
      monophasic, polycyclic, or persistent using a definition of remission requiring 3
      months of inactive disease while not receiving any therapy. Features at 3 and 6
      months are predictive of the disease course and time to remission.

PMID- 16646000
TI  - Non-enzymatic model glycation reactions--a comprehensive study of the reactivity
      of a modified arginine with aldehydic and diketonic dicarbonyl compounds by
      electrospray mass spectrometry.
AB  - Non-enzymatic glycation (Maillard reaction) of long-lived proteins is a major
      contributor to the pathology of diabetes, and possibly aging and Alzheimer's
      disease. Among the amino residues in proteins arginine plays an important role,
      and its modification by sugar moieties generates the so-called advanced glycation
      end products (AGEs). Moreover, alpha-dicarbonyl compounds have been found as the
      main participants in those modifications. Four alpha-dicarbonyl compounds,
      aldehydic and ketonic, were reacted with the modified amino acid N(alpha)-acetyl
      L-arginine (AcArg), in an attempt to establish structure/activity relationships
      for the reactivity of alpha-dicarbonyls with the amine compound. Electrospray
      ionization mass spectrometry (ESI-MS), combined with tandem mass spectrometry
      (MS/MS), was used to identify and characterize reagents, intermediates and
      reaction products. The fragmentation patterns of precursor ions showed
      similarities in all reaction systems studied, in which fragmentation of the amino
      acid residue prevails, especially for the dehydrated and/or multiple dehydrated
      precursor ions. For the non-hydrated ion species, fragmentation of the arginyl
      guanidino group was mainly observed. Specific information regarding the nature of
      the ions formed, in which the dicarbonyl electrophile character played an
      important role, was obtained. As an example, singly and doubly hydrated acetyl
      argpyrimidine ions were detected for the methylglyoxal reaction only. For
      symmetrical dicarbonyls, glyoxal and diacetyl, the importance of steric
      contributions with respect to the energetic ones is discussed. Furthermore, the
      dehydrated acetyl-tetrahydropyrimidine ions for methylglyoxal and phenylglyoxal
      reactions revealed fragment ion compositions including the protonated molecules
      of acetyl-argpyrimidine, -hydroimidazolone and -5-methylimidazolone. An
      explanation for the acetyl-argpyrimidine formation from the acetyl
      hydroimidazolone formation reaction is proposed. Aspects such as the amount of
      acetyl-hydroimidazolone formed, the response of the hydration equilibria of the
      dicarbonyl forms to the new unhydrated dicarbonyls introduced by the reversal of
      the acetyl-hydroimidazolone formation reaction and the stability of the
      dicarbonyl intermediate involved in the acetyl-argpyrimidine formation are
      proposed, as being responsible to control the formation of acetyl-argpyrimidine.

PMID- 16646001
TI  - Application of the WHO alert level framework to cyanobacterial monitoring of Lake
      Champlain, Vermont.
AB  - The increasing incidence of toxic cyanobacteria blooms worldwide has created a
      need for practical and efficient monitoring in order to protect public health. We
      developed a monitoring and alert framework based on World Health Organization
      (WHO) recommendations and applied it on Lake Champlain during the summers of 2002
      2004. The protocol began with collection of net samples of phytoplankton in order
      to maximize the chance of finding potential toxin-producing cyanobacteria.
      Samples were collected lake-wide in partnership with ongoing monitoring efforts,
      but because open water sample sites did not capture conditions along the
      shoreline, we added near-shore and shoreline stations in problem areas. Samples
      were examined qualitatively until potential toxin-producing taxa were found. Then
      quantitative analyses began, using a rapid screening method to estimate cell
      density based on colony size. A final cell density of 4000 cells/mL triggered
      toxin analyses. Primary analysis was for microcystins using ELISA methods. Cell
      densities, locations of colonies, and toxin concentrations were reported weekly
      to public health officials. We found that screening for potential toxin-producing
      cyanobacteria and then measuring toxin concentrations when cell densities reached
      critical levels worked well to identify problem locations. Although the WHO
      recommends using chlorophyll a concentration, it was not a good indicator of
      problem densities of potential toxin-producing cyanobacteria. Our cell density
      screening method missed no developing blooms but produced less precise density
      estimates at high cell counts. Overall, our framework appears to provide an
      efficient and effective method for monitoring cyanotoxin risks.

PMID- 16646002
TI  - Analysis of paralytic shellfish toxins in Aphanizomenon DC-1 from Lake Dianchi,
      China.
AB  - Lake Dianchi is in Yunnan Province in southwestern China. In recent years,
      significant cyanobacterial blooms have occurred in this lake nearly every year
      because of eutrophication. Monitoring data for the past 5 years acquired by our
      research group showed that phytoplankton composition alternated between species
      of Microcystis sp. during warm seasons and those of Aphanizomenon sp. during cool
      seasons. In March 2003, when phytoplankton composition was highly dominated by
      Aphanizomenon sp., samples were taken from the lake for toxin detection and
      immediate strain isolation. A mouse bioassay with extracts from the lyophilized
      field material showed obvious intoxication from paralytic shellfish poisons
      (PSPs), and all mice died within 30 min. Further analysis of both field and
      isolated algal strain Aphanizomenon DC-1 by the postcolumn HPLC-FLD method
      confirmed its PSP-producing ability. The analogues found in the extracts from the
      field material were neoSTX, dcSTX, and dcGTX3, with contents of 2.279, 1.135, and
      0.547 ng/mg DW, respectively. Under laboratory culture condition, toxin content
      in the Aphanizomenon strain DC-1 varied greatly during different growth phases,
      with two peaks: in the early-exponential and late-stationary growth phases. When
      the culture grew at a relatively high rate during the mid- to late-exponential
      growth phase, toxin content declined gradually. Moreover, the types of toxin in
      the DC-1 strain varied greatly during a single culture cycle. The HPLC results
      showed that dcSTX was the only toxin isomer detected throughout the culture
      period, and its level remained stable. On the other hand, dcGTX2 and GTX4 were
      the major toxins during the early-exponential and stationary phases,
      respectively. This article presents the first data on the identification and
      detection of paralytic shellfish toxins from cyanobacteria in Lake Dianchi. As
      far as we know, this is also the first report of this type of toxin in inland
      water bodies in China. Our study indicates the threat associated with PSP toxins
      in Lake Dianchi and suggests that necessary measures and programs for control are
      urgently needed to prevent the spread of toxic cyanobacterial blooms.

PMID- 16646003
TI  - A comparison of response criteria to evaluate therapeutic response in patients
      with juvenile idiopathic arthritis treated with methotrexate and/or anti-tumor
      necrosis factor alpha agents.
AB  - OBJECTIVE: There are no validated criteria to evaluate clinical response in
      juvenile idiopathic arthritis (JIA). The purpose of this study was to compare 4
      sets of criteria (2 from the American College of Rheumatology [ACR] and 2 from
      the European League Against Rheumatism [EULAR]) for clinical response evaluation
      in JIA patients treated with methotrexate and/or anti-tumor necrosis factor alpha
      drugs. METHODS: Seventy-five patients with JIA were evaluated at baseline and
      after 6 months of therapy with second-line drugs. Mean age at study onset was
      12.8 years (range 2-32.9 years). Diagnoses were systemic JIA (n = 16), rheumatoid
      factor-positive JIA (n = 5), rheumatoid factor-negative JIA (n = 9), persistent
      oligoarticular JIA (n = 10), extended oligoarticular JIA (n = 33), and psoriatic
      arthritis (n = 2). Clinical response was evaluated with the ACR Pediatric 30
      criteria and the ACR 20% response criteria (ACR20), and with the EULAR Disease
      Activity Score (DAS) and 28-joint DAS (DAS28). Patients with EULAR criteria
      responses of "good" or "moderate" were classified as responders. Responders and
      nonresponders according to the different criteria were then compared. RESULTS:
      For patients younger than 16 years, Cohen's kappa varied between 0.51 and 0.72,
      with a good-to-excellent reproducibility index for all comparisons, except for
      the DAS28/ACR20 comparison. The best agreement was obtained by comparing the DAS
      and the ACR Pediatric 30. For patients older than 16 years, the reproducibility
      index was good or excellent in only 2 cases, i.e., comparing the DAS and the ACR
      Pediatric 30 and comparing the DAS and the DAS28 (as expected). CONCLUSION: Our
      study shows a good agreement overall for the different criteria tested. The
      highest concordance was observed between the DAS and the ACR Pediatric 30, the
      lowest between the DAS28 and the ACR20. Our data suggest that the ACR Pediatric
      30 criteria can be used also in adult patients affected by JIA, and that the
      original DAS can be an alternative to the ACR Pediatric 30 in both children and
      young adults with JIA.

PMID- 16646004
TI  - Solid malignancies among patients in the Wegener's Granulomatosis Etanercept
      Trial.
AB  - OBJECTIVE: Etanercept is a soluble fusion protein designed to inhibit tumor
      necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial
      (WGET), a placebo-controlled trial of etanercept given in addition to standard
      therapy for remission induction and maintenance, more solid malignancies were
      observed in the etanercept group than in the group treated with standard therapy
      alone. This study was undertaken to further explore the potential association
      between anti-TNF therapy and the development of malignancy in these patients.
      METHODS: One hundred eighty patients with active WG were enrolled and followed up
      for a median of 27 months. At enrollment, disease characteristics, treatment
      history, specific medical history items, and information about previous WG
      treatments and risk factors for malignancy were recorded. During the trial, the
      occurrence of malignancies and other adverse events was recorded prospectively.
      RESULTS: All 6 solid malignancies observed during the WGET occurred in the
      etanercept group (P = 0.01 versus placebo group); based on a comparison of age-
      and sex-specific incidence rates, 1.92 solid malignancies would have been
      expected in this group. The solid malignancies included 2 cases of mucinous
      adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell
      carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no
      differences between the 2 treatment groups in sex distribution, disease severity,
      personal or family history of cancer, or tobacco and alcohol use. The etanercept
      group was older at baseline and less likely to be newly diagnosed with WG at the
      time of randomization. Patients who developed solid tumors were older than
      patients who did not. All etanercept-treated patients who developed solid tumors
      were also treated with cyclophosphamide during the trial. However, there were no
      differences between the groups in the amount of cyclophosphamide received during
      the trial or the percentage who had received cyclophosphamide before enrollment.
      There were also no differences in the mean duration of daily cyclophosphamide
      therapy or the maximum daily cyclophosphamide dosage before enrollment.
      CONCLUSION: Data from the WGET, the first substantial reported experience of the
      combined use of etanercept and cyclophosphamide in the treatment of WG, indicate
      that the combination of TNF inhibition and cyclophosphamide may heighten the risk
      of cancer beyond that observed with cyclophosphamide alone.

PMID- 16646005
TI  - Induced smoothing for rank regression with censored survival times.
AB  - Adaptions of weighted rank regression to the accelerated failure time model for
      censored survival data have been successful in yielding asymptotically normal
      estimates and flexible weighting schemes to increase statistical efficiencies.
      However, for only one simple weighting scheme, Gehan or Wilcoxon weights, are
      estimating equations guaranteed to be monotone in parameter components, and even
      in this case are step functions, requiring the equivalent of linear programming
      for computation. The lack of smoothness makes standard error or covariance matrix
      estimation even more difficult. An induced smoothing technique overcame these
      difficulties in various problems involving monotone but pure jump estimating
      equations, including conventional rank regression. The present paper applies
      induced smoothing to the Gehan-Wilcoxon weighted rank regression for the
      accelerated failure time model, for the more difficult case of survival time data
      subject to censoring, where the inapplicability of permutation arguments
      necessitates a new method of estimating null variance of estimating functions.
      Smooth monotone parameter estimation and rapid, reliable standard error or
      covariance matrix estimation is obtained.

PMID- 16646006
TI  - In vitro and in vivo evaluation of WK-X-34, a novel inhibitor of P-glycoprotein
      and BCRP, using radio imaging techniques.
AB  - Overexpression of the multidrug resistance proteins P-glycoprotein (Pgp) and
      breast cancer resistance protein (BCRP) results in treatment failure of many
      malignancies including ovarian cancer. Dual inhibition of Pgp and BCRP may
      restore the sensitivity of resistant cells to anticancer drugs. We report the
      synthesis and characterization of a novel anthranilic-acid based Pgp and BCRP
      modulator, WK-X-34. In vitro inhibition of Pgp activity was evaluated using 99mTc
      Sestamibi and daunorubicin accumulation in Pgp overexpressing human ovarian
      cancer cells (A2780/Adr) and its sensitive counterpart (A2780/wt). Interaction
      with BCRP was examined with a mitoxantrone-efflux assay in BCRP-overexpressing
      MCF7/mx cells, with flow cytometry. Interactions with the multidrug resistance
      associated proteins (MRP) were evaluated in transfected MRP1, MRP2 and MRP3 cell
      lines, using a 5-CFDA efflux assay. In vivo 99mTc-Sestamibi imaging of human
      ovarian cancer xenografts was used to evaluate the in vivo efficacy of WK-X-34 in
      mice. Daunorubicin accumulation in A2780/Adr cells was inhibited by WK-X-34 at
      nanomolar concentrations (IC50: 82.1 +/- 6 nM). WK-X-34 inhibited mitoxantrone
      accumulation in BCRP-overexpressing cells at micromolar concentrations (IC50 =
      26.5 +/- 4.6 microM), whereas WK-X-34 did not significantly alter 5-CFDA
      accumulation in MRP transfected cells. In vivo, uptake of 99mTc-Sestamibi was
      significantly increased in A2780/Adr xenograft tumors, brain and intestine
      (AUCs(0-4h) 136%, 147% and 138%; p < 0.05) in mice dosed with WK-X-34 (20 mg/kg
      i.p.). WK-X-34 selectively modulates Pgp and BCRP in vitro and in vivo in
      multidrug resistant ovarian cancer cells, and thus may have potential utility in
      the treatment of multidrug resistant tumors.

PMID- 16646008
TI  - HRTEM of dislocation cores and thin-foil effects in metals and intermetallic
      compounds.
AB  - Examples of the observation and analysis of dislocation cores and dislocation
      fine structure in metals and intermetallics using high resolution transmission
      electron microscopy are discussed. Specific examples include the 60 degrees
      dislocations in aluminum, a011 edge dislocations in NiAl, and screw dislocations
      in Ni3Al. The effect of the thin TEM foils on the structure and imaging of these
      dislocations is discussed in light of embedded atom method calculations for
      several configurations and coupled with image simulations. Some generalizations
      based on these calculations are discussed. These analyses enables determination
      of the spreading or decomposition of the edge component of the cores, both in and
      out of the glide plane, which can have significant implications for the modeling
      of macroscopic behavior.

PMID- 16646009
TI  - Atom probe tomography characterization of solute segregation to dislocations.
AB  - The extent and level of solute segregation to individual dislocations may be
      quantified by atom probe tomography. The technique is best applied to materials
      with high dislocation densities, such as cold worked, mechanically alloyed, or
      neutron-irradiated materials. Dislocations may be observed in field ion images by
      a change of the normal concentric atom terraces at crystallographic poles to
      spirals. Solute segregation is evident in field ion images by brightly imaging
      atoms near the core of the dislocation. Dislocations are evident in atom maps in
      the three-dimensional atom probe by linear regions of enhanced solute
      concentration. The maximum separation envelope and tracer methods may be used to
      quantify the levels of solute at the dislocation at the subnanometer scale.
      Examples of interstitial and substitutional element segregation in a mechanically
      alloyed, oxide dispersion strengthened ferrite steel and phosphorus segregation
      to dislocations in neutron-irradiated pressure vessel steels are presented.

PMID- 16646010
TI  - Scanning electron microscopy imaging of dislocations in bulk materials, using
      electron channeling contrast.
AB  - The imaging and characterization of dislocations is commonly carried out by thin
      foil transmission electron microscopy (TEM) using diffraction contrast imaging.
      However, the thin foil approach is limited by difficult sample preparation, thin
      foil artifacts, relatively small viewable areas, and constraints on carrying out
      in situ studies. Electron channeling imaging of electron channeling contrast
      imaging (ECCI) offers an alternative approach for imaging crystalline defects,
      including dislocations. Because ECCI is carried out with field emission gun
      scanning electron microscope (FEG-SEM) using bulk specimens, many of the
      limitations of TEM thin foil analysis are overcome. This paper outlines the
      development of electron channeling patterns and channeling imaging to the current
      state of the art. The experimental parameters and set up necessary to carry out
      routine channeling imaging are reviewed. A number of examples that illustrate
      some of the advantages of ECCI over thin foil TEM are presented along with a
      discussion of some of the limitations on carrying out channeling contrast
      analysis of defect structures.

PMID- 16646011
TI  - Nanometric crystal defects in transmission electron microscopy.
AB  - Transmission electron microscopy (TEM) is revisited in order to define methods
      for the identification of nanometric defects. Nanometric crystal defects play an
      important role as they influence, generally in a detrimental way, physical
      properties. For instance, radiation-induced damage in metals strongly degrades
      mechanical properties, rendering the material stronger but brittle. The
      difficulty in using TEM to identify the nature and size of such defects resides
      in their small size. TEM image simulations are deployed to explore limits and
      possible ways to improve on spatial resolution and contrast. The contrast of
      dislocation loops, cavities, and a stacking fault tetrahedra (SFT) are simulated
      in weak beam, interfering reflections (HRTEM), and scanned condensed electron
      probe (STEM) mode. Results indicate that STEM is a possible way to image small
      defects. In addition, a new objective aperture is proposed to improve resolution
      in diffraction contrast. It is investigated by simulations of the weak beam
      imaging of SFT and successfully applied in experimental observations.

PMID- 16646012
TI  - Atomic scale defect analysis in the scanning transmission electron microscope.
AB  - Z-contrast imaging and electron energy loss spectroscopy in the scanning
      transmission electron microscope provide the ability to investigate the structure
      composition-property relationship at individual defects on the atomic scale. In
      this article, the main principles behind the techniques will be described. The
      application of these methods to the analysis of individual dislocations in GaN
      will also be discussed. In this case, the atomic scale methods indicate that many
      of the structural and electronic properties of dislocations are modified by the
      presence of impurities, such as oxygen.

PMID- 16646013
TI  - Defect analysis in crystals using X-ray topography.
AB  - A brief review of X-ray topography--a nondestructive method for direct
      observation and characterization of defects in single crystals--is presented
      here. The origin and development of this characterization method and the
      different techniques derived from it are described. Emphasis is placed on
      synchrotron X-ray topography and its application in studying various crystal
      imperfections. Mechanisms of contrast formation on X-ray topographs are
      discussed, with emphasis on contrast associated with dislocations. Determination
      of Burgers vectors and line directions of dislocations from analysis of X-ray
      topographs is explained. Contrast from inclusions is illustrated, and their
      differentiation from dislocations is demonstrated with the aid of simulated
      topographs. Contrast arising from the deformation fields associated with cracks
      is also briefly covered.

PMID- 16646014
TI  - AFM study of the plastic deformation of polysynthetically-twinned (PST) TiAl
      crystals in soft orientation.
AB  - PST TiAl samples with a nominal composition of Ti52Al48 were deformed at room
      temperature with compression axis inclined to the lamellar interfaces by 45
      degrees and one of the side surface normal directions set to be (112). The
      deformation structures on the free surfaces of the deformed samples were
      investigated using Atomic Force Microscope (AFM). It was found that in-plane
      shear (shear in planes parallel to lamellar interfaces) is the dominant
      deformation mode in all gamma domains and most of the deformation traces on the
      free surfaces are parallel to lamellar interfaces. Out-of-plane shear (shear in
      planes inclined to lamellar interfaces) also occurs but contributes much less to
      the macroscopic strain. This selective activation of deformation modes leads to a
      highly anisotropic deformation behavior in PST crystals with this orientation.

PMID- 16646015
TI  - Microbial genotoxicity as an environmental indicator for near-coastal sediment
      pore waters.
AB  - The genotoxic potential of sediment pore water collected from coastal areas in
      the Gulf of Mexico has not been reported frequently in the literature. This
      report summarizes a study of the microbial mutagenicity of 31 pore water samples
      obtained from sediment affected by non-point source runoff and compares the
      results with those for more traditional chemical and biological indicators of
      sediment quality. Genotoxicity was determined pre- and post-enzyme activation
      using a proprietary short-term microbial assay for pore water centrifuged from
      sediment collected adjacent to a Florida coastal golf complex and from an
      urbanized bayou-estuary. Sediment and the associated pore water also were
      analyzed for acute toxicity to Hyallela azteca, Palaemonetes pugio, or
      Americamysis bahia and for benthic macroinvertebrate diversity (sediment only).
      Genotoxicity (direct and enzyme-activated) was detected in 4 of 17 (golf complex)
      and in 10 of 14 (urbanized bayou) pore water samples. The lowest toxic pore water
      concentrations were between 1.8% and 44.4% (direct) and between 2.6% and 25%
      (enzyme-activated). The results of the genotoxic assay paralleled those based on
      exceedance of proposed sediment quality guidelines, pore water acute toxicity and
      Shannon-Wiener diversity index values for 81%, 58%, and 65% of the comparisons,
      respectively.

PMID- 16646016
TI  - Changes in concentrations of microcystins in rainbow trout, freshwater mussels,
      and cyanobacteria in Lakes Rotoiti and Rotoehu.
AB  - Microcystin concentrations in cyanobacteria and their accumulation in rainbow
      trout (Oncorhynchus mykiss) and freshwater mussels (Hyridella menziesi) in Lakes
      Rotoiti and Rotoehu (New Zealand) were investigated. Hatchery rainbow trout were
      added to an enclosure in Lake Rotoiti where concentrations of microcystins in the
      phytoplankton and cyanobacterial cell concentrations could be closely monitored.
      Rainbow trout that were free to roam in the entire area of each lake were also
      included in the study. Freshwater mussels were suspended subsurface in cages in
      the enclosure. Phytoplankton samples, rainbow trout liver and muscle tissue, and
      the tissues of mussels were analyzed for microcystins using the ADDA-ELISA
      method, and selected samples were analyzed using LC-MS. A maximum concentration
      of microcystins in the phytoplankton samples of 760 microg L(-1) was recorded in
      Te Weta Bay, Lake Rotoiti, in March 2004. ELISA results confirmed microcystin
      immunoreactivity in rainbow trout liver and muscle tissues and in freshwater
      mussels. The microcystin congeners LR, YR, RR, AR, FR, LA, and WR were detected
      by LC-MS in caged freshwater mussels in Lake Rotoiti but were not detected in
      either muscle or liver tissue of rainbow trout. The daily tolerable intake limit
      of microcystins for human consumption recommended by the World Health
      Organisation is 0.04 microg kg(-1) day(-1). Modeling was carried out for the
      human intake of microcystin compounds from rainbow trout muscle tissue, and the
      potential health risks were estimated, assuming the ADDA-ELISA was determining
      compounds of toxicity equivalent to microcystin-LR.

PMID- 16646017
TI  - Development of an in vitro blood-brain barrier model to study the effects of
      endosulfan on the permeability of tight junctions and a comparative study of the
      cytotoxic effects of endosulfan on rat and human glial and neuronal cell
      cultures.
AB  - Endosulfan, an organochlorine (OC) insecticide that belongs to the cyclodiene
      group, is one of the most commonly used pesticides to control pests in
      vegetables, cotton, and fruits. Porcine brain microvascular endothelial cells
      were used to develop a model to study the effects of endosulfan on the
      permeability of tight junctions in the blood-brain barrier (BBB). BBB
      permeability, measured as transendothelial electrical resistance, decreased in a
      dose- and time-dependent manner when treated with alpha-endosulfan, beta
      endosulfan, or endosulfan sulfate. Cytotoxicity testing revealed that the three
      endosulfans did not cause cell death at concentrations of 10 microM and below.
      The ratio of the average permeability of the filter-grown endothelial cell
      monolayer to 14C-endosulfan (Pe) going from the outer to the inner compartments
      with that going from the inner to the outer compartments was approximately 1:1.2
      2.1 after exposure to concentrations of 0.01-10 microM. alpha-Endosulfan, beta
      endosulfan, and endosulfan sulfate had cytotoxic effects on rat glial (C6) and
      neuronal (PC12) cell cultures as well as on human glial (CCF-STTG1) and neuronal
      (NT2) cell cultures. The effects of alpha-endosulfan were highly selective, with
      a wide range of LC50 values found in the different cultures, ranging from 11.2
      microM for CCF-STTG1 cells to 48.0 microM for PC12 cells. In contrast, selective
      neurotoxicity was not so manifest in glial and neuronal cell cultures after
      exposure to endosulfan sulfate, as LC50 values were in the range of 10.4-21.6
      microM. CCF-STTG1 cells were more sensitive to alpha-endosulfan and endosulfan
      sulfate, whereas NT2 cells were more sensitive to beta-endosulfan.

PMID- 16646018
TI  - Summer changes in cyanobacterial bloom composition and microcystin concentration
      in eutrophic Czech reservoirs.
AB  - In mid-July and August 2003 and 2004, 18 reservoirs in the Czech Republic were
      sampled for phytoplankton species composition and concentration of intracellular
      microcystins (MCs). As a consequence of high nutrient loading, most of the
      reservoirs experienced cyanobacterial blooms of various intensities, with the
      prevalence of cyanobacteria increasing markedly in August, along with a
      conspicuous shift in species composition toward dominance of Microcystis spp.
      Microcystins were detected in 90% of the samples, and their amount also increased
      considerably in August, reflecting the cyanobacterial biomass. In Microcystis
      dominated samples, a significantly higher amount of MCs (p < 0.001) occurred than
      in samples in which other taxa prevailed. Microcystins were positively correlated
      with chlorophyll a and cyanobacterial biovolume (p < 0.05, R2 = 0.61 and 0.66,
      respectively), with the strongest correlation found for Microcystis spp.
      biovolume (p < 0.001, R2 = 0.87). This taxon was the most important producer of
      MCs in Czech reservoirs. The main structural variants of MCs were MC-LR, MC-RR,
      and MC-YR. This study's data also indicate that the relative share of MC variants
      (MC-LR and MC-RR) varies considerably with time, most likely as a consequence of
      different species and strain compositions during the summer. This study clearly
      demonstrates a high prevalence of MC-producing cyanobacteria in Czech reservoirs.
      Therefore, regular monitoring of these reservoirs is highly desirable in an
      effort to minimize potential health risks to the human population.

PMID- 16646019
TI  - Tributyltin contamination of bivalves in coastal areas around northern Kyushu,
      Japan.
AB  - We determined tributyltin (TBT) concentrations in bivalve samples of blue mussel
      (Myitlus edulis), Manila clam (Ruditapes philippinarum) and pen shell (Atrina
      pectinata) collected from coastal areas around northern Kyushu in 1998 and 2001.
      TBT was detected in all bivalve samples collected, ranging in concentration from
      0.008 to 0.135 microg/g wet wt. In Hakata Port, which is an industrial area, high
      TBT concentrations were detected in bivalves (blue mussel, maximum concentration
      of 0.135 microg/g wet wt). In the Ariake Sea, which is an important bivalve
      habitat, TBT concentrations in Manila clams ranged from 0.062 to 0.125 microg/g
      wet wt in 1998 and from 0.008 to 0.033 microg/g wet wt in 2001. In addition,
      concentrations of TBT in pen shells collected from the Ariake Sea in 2001 ranged
      from 0.009 to 0.095 microg/g wet wt. These results clearly demonstrate that,
      despite the regulation of TBT usage since 1990 in Japan, contamination of
      bivalves by TBT has persisted in coastal areas around northern Kyushu.

PMID- 16646020
TI  - Evaluating genotoxicity associated with microcystin-LR and its risk to source
      water safety in Meiliang Bay, Taihu Lake.
AB  - In recent years cyanobacteria blooms have become a severe problem in Taihu Lake,
      a large shallow eutrophic lake in China. Microcystins produced by certain genera
      of cyanobacteria can affect public health in this area because of their acute and
      chronic toxic effects. In this study, samples of cyanobacteria were collected and
      extracted by two solvent systems. The extracts were tested with three short-term
      genotoxicity assays, the ara test, the Ames test, and the SOS/umu test. In
      addition, temporal variation in the concentrations of microcystin-LR in the water
      samples was determined and monitored by an ELISA assay. Then the concentration of
      microcystin-LR in the drinking water was estimated. The risk of microcystin-LR
      exposure by drinking water was assessed according to tolerable daily intake
      (TDI). The three genotoxicity assays showed negative results regardless of the
      solvent system used, and there were clear inconsistencies in the spatiotemporal
      profiles of genotoxic potential and microcystin concentrations in Taihu Lake.
      Risk assessment showed that the drinking water from Taihu Lake was not safe from
      the end of July to the beginning of November because of a high concentration of
      microcystin-LR. Our study indicated the drinking water from Taihu Lake posed a
      risk because of the microcystin-LR, although it was neither genotoxic nor
      associated with genotoxicity of the lake water.

PMID- 16646021
TI  - Aquatic herbicides and herbicide contaminants: In vitro cytotoxicity and cell
      cycle analysis.
AB  - Concerns have arisen about the possible effects of herbicide contamination in
      aquatic ecosystems. Crop herbicides are introduced into the aquatic environment
      both inadvertently through runoff events and intentionally through the use of
      those registered for use in waterways. Acetochlor and atrazine are two
      agricultural crop herbicides that have often been reported to contaminate waters.
      Diquat and fluridone are both registered aquatic management herbicides. In this
      study, a mammalian in vitro cell cytotoxicity assay was used to evaluate the
      cytotoxicity of these four commonly used herbicides. The ranked order of the
      cytotoxicity was: diquat (C(1/2) = 0.036 mM +/- 0.011) > acetochlor (C(1/2) =
      0.060 mM +/- 0.010) > fluridone (C(1/2) = 0.172 mM +/- 0.029) atrazine (C(1/2) =
      0.581 mM +/- 0.050). In addition, flow cytometric analysis was conducted on CHO
      cells to investigate the potential impact of these four herbicides on the cell
      cycle. Acetochlor and diquat had the greatest impact on the cell cycle. Acetochor
      exposure resulted in a decreased number of cells in the G1 phase of the cell
      cycle, whereas diquat exposure resulted in a decreased number of cells in both
      the G1 and G2 phases. Both atrazine and fluridone resulted in a decrease in cells
      in the G2 phase. The agricultural crop herbicides and aquatic management
      herbicides gave similar results in cytotoxicity and in the cell-cycle assay at
      the end points tested.

PMID- 16646022
TI  - Comparative evaluation of genotoxicity of captan in amphibian larvae (Xenopus
      laevis and Pleurodeles waltl) using the comet assay and the micronucleus test.
AB  - Captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) is a fungicide
      used to inhibit the growth of many types of fungi on plants used as foodstuffs.
      The toxic and genotoxic potentials of captan were evaluated with the micronucleus
      test (MNT; AFNOR,2000) and the comet assay (CA) using amphibian larvae (Xenopus
      laevis and Pleurodeles waltl). Acute toxicity results showed that captan was
      toxic (1) to Xenopus larvae exposed to from 2 mg/L to 125 or 62.5 microg/L,
      depending on the nature of the water [reconstituted water containing mineral
      salts or mineral water (MW; Volvic, Danone, France)] and (2) to Pleurodeles
      exposed to from 2 mg/L to 125 microg/L in both types of water. The MNT results
      obtained in MW showed that captan (62.5 microg/L) was genotoxic to Xenopus but
      not genotoxic to Pleurodeles at all concentrations tested. CA established that
      the genotoxicity of captan to Xenopus and Pleurodeles larvae depended on the
      concentration, the exposure times, and the comet parameters (tail DNA, TEM, OTM,
      and TL). The CA and MNT results were compared for their ability to detect DNA
      damage at the concentrations of captan and the exposure times applied. CA showed
      captan to be genotoxic from the first day of exposure. In amphibians, CA appears
      to be a sensitive and suitable method for detecting genotoxicity such as that
      caused by captan.

PMID- 16646023
TI  - Mediation of endothelial cell damage by serine proteases, but not superoxide,
      released from antineutrophil cytoplasmic antibody-stimulated neutrophils.
AB  - OBJECTIVE: To evaluate potential mediators of endothelial cell injury in systemic
      vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs), we
      investigated the factors controlling the neutrophil respiratory burst and
      endothelial release of von Willebrand factor (vWF) during neutrophil-endothelial
      cell interactions. METHODS: Superoxide release from neutrophils binding to
      purified P-selectin or to tumor necrosis factor-activated endothelial cells was
      measured under flow or static conditions using the superoxide dismutase (SOD)
      inhibitable reduction of ferricytochrome c. Neutrophils were activated with fMLP,
      normal IgG, or ANCA IgG. Enzyme-linked immunosorbent assay was used to measure
      vWF. Serine protease activity was measured enzymatically. RESULTS: ANCA IgG or
      fMLP induced superoxide release when perfused over neutrophils that were rolling
      over P-selectin, but not those that were binding to endothelial cells. In static
      assays, endothelial cells inhibited superoxide production by neutrophils.
      Adenosine inhibited the respiratory burst, and, in cocultures, adenosine
      deaminase overcame the inhibitory effects of endothelial cells. Serine proteases
      were released during activated neutrophil-endothelial cell coculture. There was
      enhanced release of vWF during activated neutrophil-endothelial cell coculture;
      this was not inhibited by diphenyleneiodonium or by SOD plus catalase, but was
      inhibited by diisopropylfluorophosphate. CONCLUSION: Endothelial cells inhibit
      superoxide generation by fMLP and ANCA-activated neutrophils. The release of vWF
      occurs during coculture and is sensitive to serine protease, but not NADPH
      oxidase inhibition. Serine proteases may play a more important role than reactive
      oxygen species as mediators of endothelial injury during ANCA-associated systemic
      vasculitis.

PMID- 16646024
TI  - Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory
      arthritis.
AB  - OBJECTIVE: Intraarticular corticosteroids are frequently used as successful
      adjuvant therapy for inflammatory arthritides, but little is known about their
      effects on molecules that regulate bone biology. We undertook this study to
      investigate the effect of intraarticular corticosteroids on the synovial
      expression of RANKL and osteoprotegerin (OPG). METHODS: We evaluated RANKL, OPG,
      and surface marker expression by immunohistochemical methods in synovial knee
      biopsy samples obtained from 13 patients with inflammatory arthritis before and 2
      weeks following intraarticular injection of triamcinolone hexacetonide. We
      further investigated the effect of dexamethasone (DEX) on RANKL expression by
      lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow
      cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL
      and OPG expression in osteoblast-like cells, by Western blotting. RESULTS:
      Intraarticular corticosteroids induced a decrease in the number of synovial T
      cells without influencing the number of macrophages, evaluated as both CD68+ and
      CD163+ cells. This change was paralleled by a decrease of synovial RANKL
      expression with a concomitant reduction of the RANKL:OPG ratio. DEX down
      regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro
      pretreatment of osteoblast-like cells with tumor necrosis factor favored an
      antiresorptive effect of DEX treatment through a similar down-regulation of RANKL
      expression. CONCLUSION: The decrease in inflammation attributed to intraarticular
      corticosteroids is accompanied by down-modulation of bone destruction markers.
      These findings offer a rationale for the beneficial effect of corticosteroids on
      joint erosion in arthritis.

PMID- 16646025
TI  - Mouse monoclonal anti-human thrombomodulin antibodies bind to and activate
      endothelial cells through NF-kappaB activation in vitro.
AB  - OBJECTIVE: To clarify whether mouse monoclonal antibodies (mAb) against human
      thrombomodulin (TM), which react with human TM present on the endothelial cell
      (EC) surface, have anti-endothelial cell antibody (AECA) activity and influence
      antiinflammatory properties of human TM expressed on the EC surface in vitro.
      METHODS: Three preparations of mouse mAb against human TM that react with
      different sites of the human TM epidermal growth factor-like domain were tested
      for their ability to 1) bind to ECs, 2) modulate cytokine secretion from ECs, EC
      adhesion molecule expression, and neutrophil adhesion to ECs, and 3) stimulate
      nuclear translocation of NF-kappaB through the degradation of cytoplasmic IkappaB
      in ECs. Recombinant human interleukin-1beta (IL-1beta) was used as a positive
      control, and mouse IgG1 and mouse IgG2a were used as negative controls. RESULTS:
      The 3 preparations of mouse mAb against human TM that bind to unfixed EC
      monolayers enhanced IL-6 and IL-8 secretion from ECs, up-regulated expression of
      endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and
      intercellular adhesion molecule 1 on EC monolayers, and enhanced neutrophil
      adhesion to ECs to a degree similar to that observed with IL-1beta stimulation,
      but they did not induce the secretion of tumor necrosis factor alpha or IL-1beta
      from ECs throughout the incubation period. The 3 preparations stimulated nuclear
      translocation of NF-kappaB through the degradation of cytoplasmic IkappaB. Mouse
      IgG1 and mouse IgG2a did not exhibit such effects. CONCLUSION: These results
      suggest the possibility that AECA can react with antigens such as TM that are
      present on the EC surface and activate ECs. Such events on ECs may lead to
      vascular inflammation and damage in patients with connective tissue diseases and
      vasculitis in which AECA are present.

PMID- 16646026
TI  - Alefacept in combination with methotrexate for the treatment of psoriatic
      arthritis: results of a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of alefacept in combination with
      methotrexate (MTX) for the treatment of psoriatic arthritis (PsA). METHODS:
      Patients were eligible for this randomized, double-blind, placebo-controlled
      trial if they were ages 18-70 years and had active PsA (> or = 3 swollen joints
      and > or = 3 tender joints) despite treatment with MTX for > or = 3 months (a
      stable dosage for > or = 4 weeks prior to enrollment). Patients were stratified
      according to psoriasis body surface area (BSA) involvement (> or = 3% or < 3%).
      Alefacept (15 mg) or placebo was administered intramuscularly once weekly for 12
      weeks in combination with MTX, followed by 12 weeks of observation during which
      only MTX treatment was continued. The primary efficacy end point was the
      proportion of patients achieving a 20% improvement in disease activity according
      to the American College of Rheumatology criteria (an ACR20 response) at week 24.
      RESULTS: One hundred eighty-five patients were randomly assigned to receive
      alefacept plus MTX (n = 123) or placebo plus MTX (n = 62). At week 24, 54% of
      patients in the alefacept plus MTX group achieved an ACR20 response, compared
      with 23% of patients in the placebo plus MTX group (P < 0.001). Mean reductions
      in tender and swollen joint counts in patients receiving alefacept plus MTX were 
      8.0 and -6.3, respectively. In patients with psoriasis involving > or = 3% BSA (n
      = 87), a 50% reduction from the baseline Psoriasis Area Severity Index at week 14
      was achieved by 53% of patients receiving alefacept plus MTX compared with 17% of
      those receiving placebo plus MTX (P < 0.001). Most adverse events were mild to
      moderate in severity. In the alefacept plus MTX group, the incidence of serious
      adverse events was low (1.6%), and no opportunistic infections or malignancies
      were reported. CONCLUSION: Alefacept in combination with MTX may be an effective
      and safe treatment for PsA.

PMID- 16646027
TI  - Childhood acute lymphoblastic leukaemia in relation to population mixing around
      the time of birth in South Hungary.

PMID- 16646028
TI  - Fas activation of a proinflammatory program in rheumatoid synoviocytes and its
      regulation by FLIP and caspase 8 signaling.
AB  - OBJECTIVE: The expansion of an aggressive population of fibroblast-like
      synoviocytes (FLS) in rheumatoid arthritis (RA) synovium occurs despite their
      expression of functional death receptors and exposure to death receptor ligands.
      FLS can survive Fas challenge because of the constitutive expression of FLIP
      apoptosis inhibitor. We investigated whether Fas signaling plays a pathogenetic
      role by activating a nonapoptotic proinflammatory program in RA FLS. METHODS:
      Cultured RA FLS were stimulated with an agonistic anti-Fas antibody in the
      presence or absence of the caspase inhibitor Z-VAD-FMK or after RNA interference
      with a short hairpin RNA expression plasmid directed against FLIP. NF-kappaB and
      activator protein 1 (AP-1) activation was studied by electrophoretic mobility
      shift assays and p65 immunofluorescence analysis, and expression of messenger RNA
      (mRNA) for monocyte chemoattractant protein 1, interleukin-8, IkappaB alpha, and
      matrix metalloproteinases (MMPs) 1, 9, and 13 was examined by reverse
      transcription-polymerase chain reaction. Chemotactic activity of Fas-activated
      FLS-conditioned media was studied in Transwell migration assays. RESULTS: Fas
      stimulation activated NF-kappaB and AP-1, and this response required caspase
      activity, since Z-VAD-FMK inhibitor precluded it. FLIP was processed to p43
      protein after Fas stimulation in a caspase-dependent manner, and inhibition of
      FLIP expression resulted in reduced Fas-triggered NF-kappaB activation. Fas
      stimulation increased expression of mRNA for IkappaB alpha, MMPs, and chemokines,
      and Fas-activated RA FLS displayed increased chemotactic activity for monocytic
      cells. CONCLUSION: Fas triggering may contribute to the proinflammatory features
      of RA FLS by activating NF-kappaB and AP-1 and by expression of relevant target
      genes, such as MMPs and chemokines. Fas proinflammatory signaling is dependent
      upon caspase activity and FLIP expression. These data implicate FLIP as a
      potentially important molecular switch that turns the Fas signaling away from
      apoptosis and toward induction of a proinflammatory phenotype in RA FLS.

PMID- 16646029
TI  - Linkage analysis of rheumatoid arthritis in US and UK families reveals
      interactions between HLA-DRB1 and loci on chromosomes 6q and 16p.
AB  - OBJECTIVE: HLA is the most strongly associated locus in rheumatoid arthritis
      (RA), accounting for up to one-third of the genetic contribution. Conditioning on
      the effect of true disease loci such as HLA can lead to increased power to detect
      effects at other loci and, in addition, allows investigation of the underlying
      disease models, including interactions. The aim of this study was to detect
      susceptibility loci for RA by conditioning on HLA in a large sample of affected
      sibling pairs (ASPs) and to test for evidence of interaction between novel loci
      and HLA. METHODS: Genotype data from 3 whole-genome linkage scans for RA in a US
      population and a UK population were pooled, resulting in a combined data set of
      886 ASPs. This pooling of data increased the power to detect loci showing low
      levels of heterogeneity. Nonparametric linkage analysis was performed to identify
      regions of interest. Joint 2-locus analysis was then performed for HLA and each
      of the loci that demonstrated evidence of linkage in the 886 ASPs. RESULTS:
      Evidence for linkage was most significant at HLA (P = 4 x 10(-16)), with 7 non
      HLA loci showing some evidence for linkage (P = 0.05-0.003). Joint modeling of
      these loci with HLA provided evidence for linkage at a genome-wide significance
      level for loci on 6q (P = 2.7 x 10(-6)) and 16p (P = 2 x 10(-4)). CONCLUSION:
      These data provide the most convincing evidence to date that 6q and 16p harbor
      susceptibility genes. In addition, these loci may interact with HLA, facilitating
      the search for candidate genes within this region.

PMID- 16646030
TI  - Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive
      rheumatoid arthritis.
AB  - OBJECTIVE: To examine whether single-nucleotide polymorphisms (SNPs) of the
      interleukin-4 receptor gene IL4R influence susceptibility to, or radiographic
      progression in, rheumatoid arthritis (RA). METHODS: The contribution of 2 SNPs
      (I50V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed
      by allele-specific polymerase chain reaction in a case-control study of 471 RA
      patients and 371 healthy controls. Patients with available radiographs of the
      hands and feet obtained 2 years after disease onset (n = 302) were stratified
      retrospectively according to radiologic outcome into an erosive and a nonerosive
      group to evaluate the association between IL4R SNPs and disease progression.
      RESULTS: No differences in the genotype and allele frequencies of the I50V or
      Q551R SNPs were identified between the RA patients and healthy controls. In
      contrast, significant differences in the distribution of I50V IL4R SNP genotypes
      between patients with erosive and nonerosive disease were observed (chi2 = 15.68,
      P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1%
      of patients homozygous for the V50 allele compared with 37.0% of patients
      homozygous for the I50 allele (odds ratio 3.86, P < 0.0001). This association was
      independent of individual factors previously associated with severe disease, such
      as rheumatoid factor or the HLA-DR shared epitope. On a cellular level, the V50
      allele conferred significantly reduced responsiveness to interleukin-4, providing
      a possible mechanism for the association of the I50V IL4R polymorphism with early
      erosions in RA. CONCLUSION: Our data identify the I50V IL4R SNP as a novel
      genetic marker in RA, showing high predictive value for early joint destruction.

PMID- 16646031
TI  - Tissue-specific up-regulation of the proteasome subunit beta5i (LMP7) in
      Sjogren's syndrome.
AB  - OBJECTIVE: Sjogren's syndrome (SS) is characterized by autoimmune infiltration
      and focal accumulation of lymphocytes in the exocrine glands, with a predominance
      of CD4-positive T cells. Since these histologic findings are nonspecific,
      determination of clinical and serologic abnormalities contribute to the
      diagnosis. The aim of this study was to identify a novel, disease-specific,
      immunologically relevant marker for SS. METHODS: To analyze disease-related and
      tissue-specific expression of candidate markers, we examined biopsied minor
      salivary glands and peripheral blood mononuclear cells from patients with primary
      and secondary SS (n = 26) as well as from patients with sicca symptoms without
      autoimmune sialadenitis (n = 15). Expression of the Th1/Th2-related chemokines
      CCL3 (macrophage inflammatory protein 1alpha) and CCL2 (monocyte chemoattractant
      protein 1), CXCL7 (neutrophil-activating peptide 2 [NAP-2]), interleukin-1beta,
      inducible costimulator, and the proteasome subunits alpha3 (C9) and beta5i (LMP7)
      was analyzed at the messenger RNA (mRNA) level using real-time polymerase chain
      reaction techniques. Immunohistochemical analysis was used to identify the beta5i
      (LMP7)-expressing cell populations in minor salivary glands. RESULTS: The
      expression profiles revealed a significant up-regulation of beta5i (LMP7)
      exclusively in the salivary glands of SS patients. Immunohistochemistry confirmed
      expression of the immunoproteasome subunit beta5i (LMP7) within the acinar and
      ductal epithelial cells. No significant difference in the distinct histologic
      focus scores was evident for the expression of the markers investigated. In the
      peripheral blood compartment, the expression of CXCL7 was up-regulated both in
      primary and in secondary SS. CONCLUSION: Tissue-specific up-regulation of beta5i
      (LMP7) mRNA was shown to be characteristic of SS, indicating a disease-specific
      modulation of the proteasome system. Expression of beta5i (LMP7) represents an
      independent parameter that can be used in addition to the focus score to
      distinguish SS in biopsied labial salivary glands.

PMID- 16646032
TI  - Pervasive developmental disorders in Prader-Willi syndrome: the Leuven experience
      in 59 subjects and controls.
AB  - In the present study we investigated the co-morbidity of pervasive developmental
      disorder (PDD) in 59 Prader-Willi syndrome (PWS) individuals and in 59 non
      specific mentally retarded controls, matched for IQ, gender, and age. The
      'Pervasive Developmental Disorder Mentally Retardation Scale' (PDD-MRScale), a
      screening questionnaire based on the DSM-III-R criteria for PDD, has been applied
      in the PWS group and in the control group. Results of the present study revealed
      a striking autistic-like behavioral phenotype in the majority of the PWS
      individuals, particularly deficits in the quality of language and communication
      and of imagination and interests. This intersection with autistic symptomatology
      is an important addition to the behavioral phenotype in PWS persons. A first
      approach to delineate subtypes of autistic symptomalogy among PWS persons was
      performed. Nineteen percent of the PWS group did meet the full diagnostic DSM-III
      R criteria for PDD in comparison with 15% in the control group. Results revealed
      that a higher IQ in PWS does not protect to develop genuine PDD and that
      uniparental disomy/imprinting mutation as genetic origin seems to be an
      additional risk factor for developing genuine PDD. The results of the present
      study suggest the importance of reconsidering the commonly recognized obsessive
      compulsive like behavior in PWS persons within the broader spectrum of autism
      disorders.

PMID- 16646033
TI  - Major reduction in spinal inflammation in patients with ankylosing spondylitis
      after treatment with infliximab: results of a multicenter, randomized, double
      blind, placebo-controlled magnetic resonance imaging study.
AB  - OBJECTIVE: To determine whether the effects of anti-tumor necrosis factor alpha
      (TNFalpha) in reducing the signs and symptoms of ankylosing spondylitis (AS)
      coincide with a reduction in spinal inflammation as detected by magnetic
      resonance imaging (MRI). METHODS: Pre- and postgadolinium T1 and STIR MR images
      of the spine were acquired at baseline and at week 24 in patients with AS who
      participated in a multicenter, randomized, double-blind, placebo-controlled
      study. Patients were randomly assigned at an 8:3 ratio to receive infusions of
      infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6 and then every 6 weeks
      thereafter. MR images were obtained and evaluated independently by 2 readers who
      were blinded to the treatment allocation and time sequence of the images.
      RESULTS: A total of 194 patients in the infliximab group and 72 patients in the
      placebo group had evaluable images at baseline and week 24. About 80% of the
      patients had at least 1 active spinal lesion at baseline, as assessed by MRI. The
      improvement in the MRI Activity Score after 6 months was significantly greater in
      the patients who received infliximab (mean 5.02, median 2.72) than in those who
      received placebo (mean 0.60, median 0.0) (P < 0.001). Almost complete resolution
      of spinal inflammation was seen in most patients who received infliximab,
      irrespective of baseline activity. CONCLUSION: Patients with AS who received
      infliximab therapy showed a decrease in spinal inflammation as detected by MRI,
      whereas those who received placebo showed persistent inflammatory spondylitis.

PMID- 16646034
TI  - WAGR(O?) syndrome and congenital ptosis caused by an unbalanced
      t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH.
AB  - Aniridia usually occurs in isolation, but may also occur as part of the WAGR
      contiguous gene deletion syndrome, which includes Wilms tumor, aniridia,
      genitourinary abnormalities, and mental retardation. The aniridia and
      predisposition for Wilms tumor seen in WAGR are caused by haploinsufficiency for
      PAX 6 and WT1, respectively. We present a female infant with aniridia, bilateral
      ptosis, bilateral posterior capsular cataracts, nystagmus, left-sided glaucoma,
      microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor
      delay consistent with a clinical diagnosis of WAGR syndrome. In addition, weight
      for-height ratio at 12 months is at the 94th centile, raising the possibility of
      a diagnosis of WAGRO (WAGR + Obesity). Chromosome analysis revealed a
      translocation (11;15)(p13;p11.2) which has not been previously associated with a
      diagnosis of WAGR. Subsequent clinical WAGR fluorescent in situ hybridization
      (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A
      complete FISH-mapping of the breakpoints on chromosome 11 revealed a 7 Mb
      deletion within 11p13-11p14. The patient is examined in light of other reported
      patients with deletions and/or translocations involving the regions between 11p12
      --> 11p14 including patients with WAGR + obesity (WAGRO) as well as with other
      reported patients with aniridia and congenital ptosis.

PMID- 16646035
TI  - Connective tissue growth factor/CCN2 overexpression in mouse synovial lining
      results in transient fibrosis and cartilage damage.
AB  - OBJECTIVE: Characteristics of osteoarthritis (OA) include cartilage damage,
      fibrosis, and osteophyte formation. Connective tissue growth factor (CTGF; also
      known as CCN2), is found in high levels in OA chondrocytes and is frequently
      involved in fibrosis, bone formation, and cartilage repair. The present study was
      therefore undertaken to investigate the potential role of CTGF in OA
      pathophysiology. METHODS: We transfected the synovial lining of mouse knee joints
      with a recombinant adenovirus expressing human CTGF and measured synovial
      fibrosis and proteoglycan content in cartilage on days 1, 3, 7, 14, and 28.
      Messenger RNA (mRNA) expression in synovium and cartilage was measured on days 3,
      7, and 21. RESULTS: CTGF induced synovial fibrosis, as indicated by accumulation
      of extracellular matrix and an increase in procollagen type I-positive cells. The
      fibrosis reached a maximum on day 7 and had reversed by day 28. Levels of mRNA
      for matrix metalloproteinase 3 (MMP-3), MMP-13, ADAMTS-4, ADAMTS-5, tissue
      inhibitor of metalloproteinases 1 (TIMP-1), and transforming growth factor beta
      were elevated in the fibrotic tissue. TIMP-1 expression was elevated on day 3,
      while expression of other genes did not increase until day 7 or later. CTGF
      induced proteoglycan depletion in cartilage as early as day 1. Maximal depletion
      was observed on days 3-7. Cartilage damage was reduced by day 28. A high level of
      MMP-3 mRNA expression was found in cartilage. CTGF overexpression did not induce
      osteophyte formation. CONCLUSION: CTGF induces transient fibrosis that is
      reversible within 28 days. Overexpression of CTGF in knee joints results in
      reversible cartilage damage, induced either by the high CTGF levels or via
      factors produced by the CTGF-induced fibrotic tissue.

PMID- 16646036
TI  - A novel role for suppressor of cytokine signaling 3 in cartilage destruction via
      induction of chondrocyte desensitization toward insulin-like growth factor.
AB  - OBJECTIVE: An important mechanism contributing to cartilage destruction in
      arthritis is chondrocyte desensitization toward its main anabolic factor, insulin
      like growth factor 1 (IGF-1). In this study, we sought to determine the role of
      suppressor of cytokine signaling 3 (SOCS-3) in the induction of IGF-1
      desensitization of murine chondrocytes. METHODS: Chondrocyte responsiveness to
      IGF-1 was assessed by 35S-sulfate incorporation into proteoglycans (PGs), via
      aggrecan messenger RNA expression, using quantitative real-time polymerase chain
      reaction or insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation
      (Western blot analysis). IGF-1 desensitization of patellar chondrocytes was
      studied in zymosan-induced arthritis. IGF-1 desensitization was induced in
      patellar cartilage explants or the H4 chondrocyte cell line, exposed to
      interleukin-1alpha (IL-1alpha). SOCS-3 protein expression was assessed by
      immunohistochemistry or by Western blot analysis of protein extracts. The role of
      SOCS-3 in IGF-1 signaling was elucidated by adenoviral overexpression. RESULTS:
      Exposure of murine articular cartilage to IL-1 caused a significant decrease in
      IGF-1-induced PG synthesis. This effect also occurred in inducible nitric oxide
      synthase-knockout mice, revealing the involvement of a secondary IL-1-induced
      factor other than nitric oxide. We showed that IL-1 significantly up-regulated
      SOCS-3 transcription and protein synthesis in H4 chondrocytes. In contrast, IL-18
      was unable to induce SOCS-3 expression and failed to induce chondrocyte IGF-1
      desensitization. Histologic analysis of samples from arthritic knee joints
      revealed high expression of SOCS-3 in chondrocytes. Through adenoviral
      overexpression of SOCS-3, we obtained direct evidence that SOCS-3 inhibits IGF-1
      mediated cell signaling, since IRS-1 phosphorylation was reduced. CONCLUSION:
      This study demonstrates that IL-1-induced SOCS-3 expression is a novel mechanism
      of IGF-1 desensitization in chondrocytes; in conjunction with nitric oxide it can
      contribute to cartilage damage during arthritis.

PMID- 16646037
TI  - Increase in bone marrow lesions associated with cartilage loss: a longitudinal
      magnetic resonance imaging study of knee osteoarthritis.
AB  - OBJECTIVE: Although bone marrow lesions (BMLs) are powerful predictors of joint
      space loss as visualized on radiographs, the natural history of these lesions,
      their relationship to cartilage loss, and the association between change in these
      lesions and cartilage loss are unknown. These questions were tested using
      longitudinal magnetic resonance imaging (MRI) data in a natural history study of
      symptomatic knee osteoarthritis (OA). METHODS: MRI of the knee was performed at
      baseline, 15 months, and 30 months in 217 patients with primary knee OA (122 men,
      95 women; mean +/- SD age 66.4 +/- 9.4 years). To assess mechanical alignment,
      long-limb films were obtained at 15 months. Subchondral bone marrow
      abnormalities, graded in the medial and lateral tibiofemoral joints, were defined
      as poorly marginated areas of increased signal intensity in the marrow on fat
      suppressed, T2-weighted images. Cartilage morphologic features in the medial and
      lateral tibiofemoral joints were scored at all time points using a
      semiquantitative scale. For each of the medial and lateral compartments,
      generalized estimating equations were used to evaluate the longitudinal
      relationship of tibiofemoral BMLs to the tibiofemoral cartilage score, with
      adjustment for malalignment. RESULTS: Fifty-seven percent of knees had BMLs at
      baseline, of which 99% remained the same or increased in size at followup. Knee
      compartments with a higher baseline BML score had greater cartilage loss. An
      increase in BMLs was strongly associated with further worsening of the cartilage
      score. Enlarging or new BMLs occurred mostly in malaligned limbs, on the side of
      the malalignment (e.g., new medial BMLs in varus-aligned knees). The association
      of BML change with medial tibiofemoral cartilage loss was not significant after
      adjusting for alignment. CONCLUSION: Lesions of the bone marrow are unlikely to
      resolve and often get larger over time. Compared with BMLs that stay the same,
      enlarging BMLs are strongly associated with more cartilage loss. Furthermore, any
      change in BML is mediated by limb alignment.

PMID- 16646038
TI  - Functional characterization of a soluble gp130 isoform and its therapeutic
      capacity in an experimental model of inflammatory arthritis.
AB  - OBJECTIVE: Soluble gp130 is the naturally occurring antagonist of the interleukin
      6 (IL-6)/soluble IL-6 receptor (sIL-6R) complex and selectively inhibits IL-6
      trans-signaling. Several isoforms of soluble gp130 have been identified,
      including an autoantigenic form termed gp130-RAPS (for gp130 of the rheumatoid
      arthritis antigenic peptide-bearing soluble form) that is present in the serum
      and synovial fluid of patients with rheumatoid arthritis. The aim of this study
      was to evaluate the functional properties of gp130-RAPS. METHODS: To define a
      role for gp130-RAPS in arthritis, a recombinant version was generated using a
      baculovirus expression system, and its activities were tested in vitro and in
      vivo. RESULTS: Gp130-RAPS was shown to bind with high affinity to the stable IL
      6/sIL-6R complex, hyper-IL-6, and to effectively modulate leukocyte migration in
      murine acute peritonitis. A single intraarticular injection of gp130-RAPS
      suppressed chronic antigen-induced arthritis in association with a reduction in
      local activation of signal transducer and activator of transcription 3. Although
      gp130-RAPS contains the previously identified autoantigenic sequence Asn-Ile-Ala
      Ser-Phe (NIASF), no increase in the prevalence of anti- gp130-RAPS antibodies was
      observed in serum or synovial fluid obtained from patients with rheumatoid
      arthritis. CONCLUSION: The use of inhibitory antibodies to block IL-6 responses
      has shown considerable clinical promise. However, the results presented herein
      suggest that selective targeting of IL-6 trans-signaling may represent a viable
      alternative to this strategy. In this respect, our present results suggest that
      the soluble gp130 isoform gp130-RAPS may be useful in the treatment of chronic
      inflammatory arthritis.

PMID- 16646039
TI  - Hyaluronan molecular reflection by synovial lining is concentration dependent and
      reduced in dilute effusions in a rabbit model.
AB  - OBJECTIVE: Hyaluronan (HA) has a major role in regulating synovial fluid volume.
      This role depends on the synovium functioning as an ultrafilter that reflects HA
      during trans-synovial fluid drainage. Reflection boosts the HA concentration on
      the membrane surface, leading to osmotic retention of synovial fluid
      ("buffering"). In arthritic effusions, however, HA concentration and osmotic
      buffering are greatly reduced. We tested the hypothesis that reflection is
      reduced (escape increased) when the HA concentration falls below the molecular
      entanglement concentration (C*). METHODS: HA at 0.2 mg/ml (<C*) or 1.5 mg/ml
      (>C*) was infused continuously into rabbit knee joints to set up a steady trans
      synovial filtration. Joint-derived lymph was sampled over 3 hours, and
      subsynovial fluid was sampled at the end of the 3-hour period. HA was quantified
      by high-performance liquid chromatography to evaluate the reflected fraction. C*
      was determined by viscometry. RESULTS: Viscometry showed that 0.2 mg/ml HA was
      below C* and 1.5 mg/ml was above it. At 0.2 mg/ml, the mean +/- SEM HA reflected
      fraction was 0.66 +/- 0.04 (n = 7). At 1.5 mg/ml the reflection increased to 0.88
      +/- 0.04 (n = 5) (P < 0.005). HA permeation increased almost 3-fold, from 12% to
      34%, at the lower concentration. CONCLUSION: Chain-chain interaction at >C*
      increases effective molecular domain size and hence HA reflection, promoting
      effective conservation of synovial fluid in normal joints. HA can fall below C*
      (approximately 1 mg/ml) in arthritic effusions, promoting loss of HA. The
      attendant failure of outflow buffering facilitates fluid escape and periarticular
      edema.

PMID- 16646040
TI  - Importance of genetic influences on chronic widespread pain.
AB  - OBJECTIVE: To estimate the relative importance of genetic and environmental
      factors in chronic widespread pain, and to assess whether there are sex
      differences in the type or magnitude of these influences. METHODS: Data were
      collected from a national sample of twins > or = 42 years of age, all of whom
      were participants in the Swedish Twin Registry. The presence of chronic
      widespread pain was assessed via computer-assisted telephone interviews, which
      were conducted between 1998 and 2002, using the American College of Rheumatology
      criteria for fibromyalgia. No clinical examinations were performed. In
      preliminary analyses, probandwise concordance rates and tetrachoric correlations
      were calculated. Structural equation modeling was then performed to estimate
      additive genetic, shared environmental, and nonshared environmental sources of
      variability in susceptibility for the development of chronic widespread pain.
      RESULTS: Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the
      interview. Both members of 15,950 pairs responded to the items regarding pain
      symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic,
      and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain
      was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance
      rates and tetrachoric correlations suggested modest genetic influences for both
      women and men. Genetic and shared environmental influences explained
      approximately half of the total variance, with no indication of sex differences
      in either the type or magnitude of these influences. CONCLUSION: Individual
      differences in the likelihood of developing chronic widespread pain reflect
      modest genetic influences. There are no significant sex differences in the type
      or expression of the genes responsible for chronic widespread pain or in the
      magnitude of the relative importance of these influences on chronic widespread
      pain.

PMID- 16646041
TI  - Brachio-cervical inflammatory myopathies: clinical, immune, and myopathologic
      features.
AB  - OBJECTIVE: To characterize patients with inflammatory myopathies who present with
      weakness in the proximal regions of the arms. METHODS: Clinical, laboratory, and
      myopathologic features were evaluated in 10 patients, identified consecutively
      over 12 years, with inflammatory myopathies and weakness that was most severe in
      the proximal regions of the arms. The features of these brachio-cervical
      inflammatory myopathy (BCIM) syndromes were compared with those of other
      inflammatory and immune-mediated myopathies evaluated during the same period.
      RESULTS: Patients with BCIM developed progressive weakness at ages 24-82 years
      (mean +/- SD age 55 +/- 9 years). Posterior neck weakness occurred in 60% of
      patients, while motor neuron disease was the referring diagnosis in 30%. All
      patients had other systemic autoimmune disorders, including myasthenia gravis
      (40%) and rheumatoid arthritis (20%). Antinuclear antibodies were present in all
      patients. Serum creatine kinase levels were usually moderately high (mean 910
      IU/liter). Active myopathy was identified in muscle biopsy samples from the
      patients. Focal collections of mononuclear cells, some predominantly B cells,
      were present in perivascular and perimysial regions. MxA- and CD123-positive
      dendritic cells were present in the endomysium. C5b-9 components of complement
      were present diffusely in endomysial connective tissue. Most patients improved in
      strength after receiving corticosteroids. CONCLUSION: Patients with BCIM
      syndromes have progressive weakness in the proximal regions of the arms and neck.
      The predominant myopathologic findings are active myopathy, C5b-9 staining of
      endomysium, focal perivascular and perimysial inflammation, often with a
      prominent B cell component, and endomysial dendritic cells. Corticosteroid
      treatment of BCIM is often followed by improvement in strength.

PMID- 16646042
TI  - Recovery from deafness in a patient with Muckle-Wells syndrome treated with
      anakinra.
AB  - Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease
      characterized by rashes, fever, arthralgia, sensorineural deafness, and the
      possible development of systemic AA amyloidosis. We used anakinra to treat a 22
      year-old patient with MWS who had deafness and a high serum level of C-reactive
      protein (CRP). Following treatment with anakinra, the patient's CRP level
      normalized, and she recovered from deafness. The fact that this occurrence has
      never been previously reported strengthens the role of anakinra in MWS but also
      raises new questions about the physiopathology of such deafness.

PMID- 16646043
TI  - Anti-cyclic citrullinated peptide antibodies in psoriasis patients without
      arthritis.

PMID- 16646044
TI  - Systemic lupus erythematosus in a multiethnic US cohort: XXXVI. Influence of
      mannose-binding lectin exon 1 polymorphisms in disease manifestations, course,
      and outcome.

PMID- 16646045
TI  - Familial thoracic aortic aneurysms and dissections: three families with early
      onset ascending and descending aortic dissections in women.
AB  - Ascending thoracic aortic aneurysms leading to type A dissections can be
      inherited in an autosomal dominant manner with variable age of onset and
      decreased penetrance, primarily in women. Three families are described with
      autosomal dominant inheritance of either ascending aortic aneurysms leading to
      type A dissections or type B dissections, and a young age of onset of aortic
      dissections in both men and women. Pedigree analysis suggests that a de novo
      mutation is responsible for the disease in one family. The discordant age of
      onset of aortic disease in a monozygotic twin pair in a different family
      indicates that environmental or stochastic factors may influence the variable
      expression of disease. Genetic analysis of one family excluded linkage to known
      loci for TAAD (TAAD1, TAAD2, FAA1, or FBN1) and sequence analysis failed to
      identify mutations in TGFBR2, the gene encoding transforming growth factor beta
      receptor type II. Thus, a novel unidentified loci may be responsible for the
      phenotype in these three families.

PMID- 16646046
TI  - Flow cytometry analysis of gap junction-mediated cell-cell communication:
      advantages and pitfalls.
AB  - BACKGROUND: Since the first morphological description of the gap junctions use
      electron microscopy, a considerable number of techniques has been introduced to
      evaluate gap junction channel functionality, many of which use dye transfer
      techniques, such as dye injection and fluorescent dye transfer, analyzed by flow
      cytometry. METHODS: To analyze dye transfer, generally one population of cells is
      incubated with calcein-AM (0.5 microM) for 30 min at 37 degrees C, and the other
      population was incubated with the lipophilic dye DiIC(18) (3) (10 microM) for 1 h
      at 37 degrees C; after incubation, these cells were washed five times with PBS
      and cocultured for different times, and then the dye transfer was analyzed by
      flow cytometry. RESULTS: In this short overview, we focus on some advantages and
      disadvantages of flow cytometry as a technique to investigate gap junction
      mediated intercellular communication (GJIC). In addition, we point out some
      technical pitfalls that we have encountered when applying this technique to study
      gap junctions in immune system cells. CONCLUSIONS: Analysis of fluorescent dye
      transfer by flow cytometry is a useful tool to investigate GJIC. However, some
      points must be taken into consideration before using this methodology, which are
      discussed herein.

PMID- 16646047
TI  - Novel method for cell debris removal in the flow cytometric cell cycle analysis
      using carboxy-fluorescein diacetate succinimidyl ester.
AB  - BACKGROUND: Cell cycle analysis with flow cytometry using propidium iodide (PI)
      can be difficult in some cases because of the cell debris. Here, we introduce
      debris removal using intranuclear protein staining (DRIPS), a novel method for
      separating intact nuclei and cell debris to different populations using carboxy
      fluorescein diacetate succinimidyl ester (CFSE). METHODS: To study the apoptosis
      sensitivity, chicken DT40 B cell lymphoma cell line was gamma irradiated. After
      the irradiation, the cells were incubated up to 8 h and the stages of the cell
      cycle were followed with flow cytometry. RESULTS: CFSE staining, done
      simultaneously with PI, stained the cell debris brighter than intact nuclei and
      could be excluded from the histogram with a simple gating procedure. The method
      is reliable and reproducible and can be executed within 15 min. CONCLUSIONS:
      DRIPS-method greatly enhances the analysis of difficult cell cycle samples.

PMID- 16646048
TI  - Automated fluorescent in situ hybridization (FISH) analysis of t(9;22)(q34;q11)
      in interphase nuclei.
AB  - BACKGROUND: For chronic myeloid leukemia, the FISH detection of t(9;22)(q34;q11)
      in interphase nuclei of peripheral leukocytes is an alternative method to bone
      marrow karyotyping for monitoring treatment. With automation, several drawbacks
      of manual analysis may be circumvented. In this article, the capabilities of a
      commercially available automated image acquisition and analysis system were
      determined by detecting t(9;22)(q34;q11) in interphase nuclei of peripheral
      leukocytes. METHODS: Three peripheral blood samples of normal adults, 21 samples
      of CML patients, and one sample of a t(9;22)(q34;q11) positive cell-line were
      used. RESULTS: Single nuclei with correctly detected signals amounted to 99.6% of
      nuclei analyzed after exclusion of overlapping nuclei and nuclei with incorrect
      signal detection. A cut-off value of 0.84 mum was defined to discriminate between
      translocation positive and negative nuclei based on the shortest distance between
      signals. Using this value, the false positive rate of the automated analysis for
      negative samples was 7.0%, whereas that of the manual analysis was 5.8%.
      Automated and manual results showed strong correlation (R(2) = 0.985), the mean
      difference of results was only 3.7%. CONCLUSIONS: A reliable and objective
      automated analysis of large numbers of cells is possible, avoiding interobserver
      variability and producing statistically more accurate results than manual
      evaluation.

PMID- 16646049
TI  - Identification of organ-specific T cell populations by analysis of multiparameter
      flow cytometry data using DNA-chip analysis software.
AB  - BACKGROUND: The analysis of cells from multiple experimental groups by
      multiparameter flow cytometry leads to the generation of complex data sets, for
      which adequate analysis tools are not commonly available. We report here that
      software designed for transcriptomics applications can be used in multiparameter
      flow cytometry. METHODS: Lymphocytes isolated from nine different mouse organs
      were stained and subjected to 10-parameter flow cytometry. The resulting data set
      contained 594 different T cell subsets per organ per mouse and was organized into
      a so-called flow cytometry array (FCA). RESULTS: Computation of a hierarchical
      tree revealed that lymph nodes and spleen were populated by similar T cell
      subsets, while T cells from peripheral organs displayed a diverse subset
      composition. Furthermore, organ-specific T cell subsets were identified.
      CONCLUSIONS: This new FCA concept in flow cytomics proved to be a valuable tool
      for the fast and unbiased analysis of complex multiparameter flow cytometry data
      sets. It can be used for assessing disease progression and therapeutic
      intervention, and for the association of disease-related biomarkers on the
      protein level.

PMID- 16646050
TI  - Breast cancer risk in relation to abortion: Results from the EPIC study.
AB  - The role of spontaneous and induced abortion on breast cancer risk is examined
      among 267,361 women recruited into the European Prospective Investigation into
      Cancer and nutrition between 1992 and 2000. The data were collected from 20
      centers, across 9 countries, and included information on a total of 4,805 women
      with breast cancer, of whom 1,657 reported having ever had any type of abortion.
      Overall, the relative risk of breast cancer in women who reported ever having had
      a spontaneous abortion was not significantly elevated when compared with women
      who reported never having had such an abortion (RR = 1.07, 95% CI = 0.99-1.14).
      However, there was some evidence of a slight increase in the risk of breast
      cancer among women who reported having had 2 or more spontaneous abortions (1.20,
      1.07-1.35). The relative risk of breast cancer among women who reported ever
      having had an induced abortion when compared to women who reported never having
      had an induced abortion was 0.95 (0.87-1.03). Overall, the findings provide
      further unbiased evidence of the lack of an adverse effect of induced abortion on
      breast cancer risk.

PMID- 16646051
TI  - Body weight and postmenopausal breast cancer risk defined by estrogen and
      progesterone receptor status among Swedish women: A prospective cohort study.
AB  - Although obesity is one of the established risk factors for postmenopausal breast
      cancer, it is not clear whether this positive association differs across estrogen
      receptor (ER) and progesterone receptor (PR) status of breast tumors. We
      evaluated the association between body weight and ER/PR defined breast cancer
      risk stratified by postmenopausal hormone (PMH) use and a family history of
      breast cancer in the population-based Swedish Mammography Screening Cohort
      comprising 51,823 postmenopausal women. Relative body weight was measured by body
      mass index (kg/m2) based on self-reported weight and height collected in 1987 and
      1997. Relative risks (RRs) were estimated by hazard ratios derived from Cox
      proportional hazards regression models. During an average of 8.3-year follow-up,
      1,188 invasive breast cancer cases with known ER and PR status were diagnosed.
      When comparing to normal weight group, we observed a positive association between
      obesity and risk for the development of ER+ PR+ tumors (RR = 1.67, 95% CI = 1.34
      2.07) and an inverse association for the development of all PR- tumors (RR =
      0.68, 95% CI = 0.47-0.98). Statistically significant heterogeneity was observed
      in the RRs between ER+ PR+ tumors and all PR- tumors (p(heterogeneity) < 0.0001).
      The positive association of obesity with the development of ER+ PR+ tumors was
      confined to never-users of PMHs (RR = 1.90 (CI 95%:1.38-2.61)) and to those
      without a family history of breast cancer (RR = 1.82 (CI 95%:1.45-2.29)). Our
      results support the hypothesis that excess endogenous estrogen due to obesity
      contributes to an increased risk of ER+ PR+ postmenopausal breast cancer.

PMID- 16646052
TI  - High birth weight increases mammary tumorigenesis in rats.
AB  - Epidemiological studies have investigated whether a high birth weight is
      associated with increased breast cancer risk, but the results remain
      inconclusive. This study was designed to determine whether high birth weight
      increases later susceptibility to carcinogen-induced mammary tumorigenesis in an
      animal model and to determine mechanisms mediating this association. Pregnant
      female Sprague Dawley rats were fed either a control or a high-fat diet during
      the extent of gestation. Maternal exposure to the high-fat diet increased
      pregnancy leptin levels and offspring's birth weight, but had no effect on
      pregnancy estradiol or insulin-like growth factor 1 levels. Changes in the
      offspring's mammary gland morphology and protein expression were assessed. The
      mammary epithelial tree of the high-birth-weight offspring was denser, contained
      more terminal end buds and exhibited higher number of proliferating cells.
      Further, their mammary glands expressed lower levels of ER-alpha, but higher
      levels of activated MAPK. No alterations in apoptosis were noted. High-birth
      weight rats developed 7,12-dimethylbenz[a]anthracene-induced mammary tumors
      significantly earlier, and tumors grew larger than in the controls. The tumors in
      this group expressed higher levels of leptin receptor and activated Akt, and
      contained fewer apoptotic cells than those in the controls. Our results indicate
      that high birth weight is related to shortened latency to develop mammary tumors-
      perhaps reflecting an increase in activated MAPK levels and increased tumor
      growth--perhaps caused by a lower apoptotic response due to higher leptin
      receptor and activated Akt levels in the tumors.

PMID- 16646053
TI  - Serum concentrations of Dickkopf-1 protein are increased in patients with
      multiple myeloma and reduced after autologous stem cell transplantation.
AB  - Dickkopf-1 (DKK-1) protein, a soluble inhibitor of Wnt signalling, has been
      implicated in the pathogenesis of myeloma bone disease through the suppression of
      osteoblast differentiation. In this study, serum concentrations of DKK-1 were
      measured in 50 myeloma patients (32 at diagnosis and 18 before and after
      autologous stem cell transplantation (ASCT), 18 patients with monoclonal
      gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum
      DKK-1 levels were increased in MM at diagnosis compared with MGUS (mean +/- SD:
      67 +/- 54 ng/mL vs. 38 +/- 13 ng/mL; p = 0.006) and controls (31 +/- 11 ng/mL; p
      = 0.02), while there was no difference between MGUS patients and controls.
      Although patients with stage 2 and 3 myeloma had higher DKK-1 values than stage 1
      patients (79 +/- 63 vs. 40 +/- 13; p = 0.005), no significant correlation between
      serum DKK-1 and myeloma bone disease was observed. Myeloma patients before ASCT
      also had increased levels of DKK-1 (63 +/- 77 ng/mL; p = 0.03) compared with
      controls, supporting the notion that DKK-1 may be responsible for the suppressed
      osteoblast activity even in patients with low tumor burden. After ASCT, there was
      a sustained decrease in DKK-1 levels over time, while bone formation markers
      elevated, suggesting that the reduction of DKK-1 levels after ASCT may correlate
      with the normalization of osteoblast function. These results could provide the
      basis for developing agents that block DKK-1, thus restoring osteoblast function
      and counteracting the increased osteoclastogenesis observed in myeloma.

PMID- 16646054
TI  - Dietary folate is associated with p16(INK4A) methylation in head and neck
      squamous cell carcinoma.
AB  - Inactivation of the p16(INK4A) (CDKN2A) gene in the Rb pathway is among the most
      common somatic alterations observed in tobacco-related solid tumors, including
      head and neck squamous cell carcinoma (HNSCC). In addition, a low folate diet is
      an important risk factor for HNSCC. Decreased dietary folate in an animal model
      of hepatocellular carcinoma has been associated with the induction of epigenetic
      silencing of the p16(INK4A) gene. In an ongoing population-based study of HNSCC,
      we sought to extend this observation to human disease testing the hypothesis that
      p16(INK4A) methylation is associated with decreased dietary folate. We also
      investigated the association of methylation silencing with functional
      polymorphisms in the folate metabolism enzyme methylene tetrahydrofolate
      reductase (MTHFR). In 169 HNSCCs, the odds ratio for p16(INK4A) methylation among
      those with low dietary folate intake was 2.3 (95% CI = 1.1-4.8) when compared
      with those with high folate intake. Furthermore, this increased risk for
      epigenetic silencing at p16(INK4A) was modified by the MTHFR alleles previously
      associated with diminished serum folate levels. Hence, in HNSCC low dietary
      intake of folate is associated with p16(INK4A) methylation, and this relationship
      is modified by the MTHFR genotype. Our data provides important evidence for a
      mechanism of action of folate deficiency in cancer.

PMID- 16646055
TI  - High salt diets dose-dependently promote gastric chemical carcinogenesis in
      Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin
      production from glandular to surface mucous cells.
AB  - Intake of salt and salty food is known as a risk factor for gastric
      carcinogenesis. To examine the dose-dependence and the mechanisms underlying
      enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea
      (MNU), Helicobacter pylori and food containing various concentrations of salt,
      and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori,
      the incidences of glandular stomach cancers were 15% in the normal diet group and
      33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent
      increase (p < 0.01). Intermittent intragastric injection of saturated NaCl
      solution, in contrast, did not promote gastric carcinogenesis. In gerbils
      infected with H. pylori, a high salt diet was associated with elevation of anti
      H. pylori antibody titers, serum gastrin levels and inflammatory cell
      infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the
      amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori
      colonization, despite no increment of MUC5AC mRNA, while H. pylori infection
      itself had an opposing effect, stimulating transcription of MUC6 and increasing
      the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased
      the amount of GMCM, which acts against H. pylori infection. In conclusion, the
      present study demonstrated dose-dependent enhancing effects of salt in gastric
      chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with
      alteration of the mucous microenvironment. Reduction of salt intake could thus be
      one of the most important chemopreventive methods for human gastric
      carcinogenesis.

PMID- 16646057
TI  - Does obesity play a role in functional capacity and inflammation in patients with
      lupus? Comment on the article by Oeser et al.

PMID- 16646060
TI  - Chemokine receptor expression by peripheral blood B lymphocytes in patients with
      primary Sjogren's syndrome: comment on the article by Hansen et al.

PMID- 16646062
TI  - Effect of folic acid supplementation on the efficacy of methotrexate treatment in
      rheumatoid arthritis: comment on the article by Khanna et al.

PMID- 16646064
TI  - Giant cell arteritis revealed by positron emission tomography.

PMID- 16646066
TI  - Biocompatibility of elastin-like polymer poly(VPAVG) microparticles: in vitro and
      in vivo studies.
AB  - Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of
      proteinaceous polymer belonging to the Elastin-like family. These polymers are
      based on the recurrence of certain short peptide monomers that are considered as
      "building blocks" in the natural elastin. This smart thermoresponsive polymer has
      the ability to self-associate at physiological temperature to form aggregates
      with about 60% in water. This ability can be harnessed to prepare microparticles
      loaded with an active substance. The aim of this report is to evaluate, from the
      results of the experiment conducted, the biocompatibility of microparticles
      prepared from poly(VPAVG). We have studied the cytotoxic effects of
      microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in
      rats (n = 6), and also intraocular tolerance after the intravitreal injection of
      2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer
      did not induce any cytotoxicity or nonspecific depression of cellular respiration
      on macrophages under the range of polymer concentrations investigated in this
      study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to
      microparticles after subcutaneous injection in the hind-paw of rats, with no
      significant differences between the control group (PBS) and experimental groups.
      Anterior and posterior segment signs were evaluated after intraocular injection
      of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group
      presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of
      the eyes receiving microparticles showed tractional retinal detachment. The
      results observed in this work suggested certain fibroblastic activity induced by
      poly(VPAVG) microparticles after their intraocular injection.

PMID- 16646067
TI  - Silicon addition to hydroxyapatite increases nanoscale electrostatic, van der
      Waals, and adhesive interactions.
AB  - The normal intersurface forces between nanosized probe tips functionalized with
      COO(-)-terminated alkanethiol self-assembling monolayers and dense,
      polycrystalline silicon-substituted synthetic hydroxyapatite (SiHA) and phase
      pure hydroxyapatite (HA) were measured via a nanomechanical technique called
      chemically specific high-resolution force spectroscopy. A significantly larger
      van der Waals interaction was observed for the SiHA compared to HA; Hamaker
      constants (A) were found to be A(SiHA) = 35 +/- 27 zJ and A(HA) = 13 +/- 12 zJ.
      Using the Derjaguin-Landau-Verwey-Overbeek approximation, which assumes linear
      additivity of the electrostatic double layer and van der Waals components, and
      the nonlinear Poisson-Boltzmann surface charge model for electrostatic double
      layer forces, the surface charge per unit area, sigma (C/m(2)), was calculated as
      a function of position for specific nanosized areas within individual grains.
      SiHA was observed to be more negatively charged than HA with sigma(SiHA) = -0.024
      +/- 0.013 C/m(2), two times greater than sigma(HA) = -0.011 +/- 0.006 C/m(2).
      Additionally, SiHA was found to have increased surface adhesion (0.7 +/- 0.3 nN)
      compared to HA (0.5 +/- 0.3 nN). The characterization of the nanoscale variations
      in surface forces of SiHA and HA will enable an improved understanding of the
      initial stages of bone-biomaterial bonding.

PMID- 16646068
TI  - Down-regulation of ASY/Nogo transcription associated with progression of adult T
      cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human
      leukemia/lymphoma. Although this disease is initiated by infection with human T
      lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long
      period without aggressive illness, suggesting that other factors may play roles
      in the progression of ATLL to an aggressive state. However, the mechanism
      involved in this progression still remains unclear. Previously, we have reported
      that ASY/Nogo mRNA was markedly down-regulated in human small-cell lung
      carcinomas, whereas it was expressed in normal tissues and other lung carcinomas,
      such as adenocarcinoma and squamous cell carcinoma. To understand whether or not
      ASY/Nogo gene is involved in the progression of ATLL, we examined the expression
      of ASY/Nogo mRNA in smoldering, chronic and aggressive ATLL, and found that the
      expression level of ASY/Nogo mRNA was markedly reduced in clinically aggressive
      ATLL. HTLV-1 Tax expression was not affected by the down-regulation of ASY/Nogo
      mRNA. These results indicate that the ASY/Nogo gene may act as a suppressor
      against ATLL progression, independent of Tax expression.

PMID- 16646069
TI  - Genetic polymorphisms of the XPG and XPD nucleotide excision repair genes in
      sarcoma patients.
AB  - There are more than 50 subtypes of soft tissue sarcomas, among which 30% are
      associated with specific genetic alterations, including translocations. Several
      studies have reported associations between cancer risk and polymorphisms of DNA
      repair genes from the nucleotide excision repair (NER) pathway. NER involves more
      than 20 proteins whose inactivation leads to xeroderma pigmentosum (XP) or
      cockayne syndrome (CS), among which XPD, a helicase allowing DNA strand excision
      by the endonuclease XPG. DNA from 93 patients with synovial sarcomas, myxoid
      liposarcomas, dermatofibrosarcomas protuberans (DFSP), malignant fibrous
      histiocytomas and leiomyosarcomas were genotyped for both XPD Lys751Gln and XPG
      Asp1104His polymorphisms. Departure from Hardy-Weinberg was highly significant
      for the XPG polymorphism with an excess of heterozygotes in synovial sarcomas (p
      = 1.5 x 10(-5)), myxoid liposarcomas (p = 1.5 x 10(-4)) and to a lesser extent in
      DFSP (p = 0.028). In the case of XPD, a significant deviation was observed in
      synovial sarcomas (p = 3 x 10(-6)) and DFSP (p = 0.0014). When tumors were pooled
      according to their genetic alterations, the proportion of carriers of the variant
      XPG allele was significantly increased in sarcomas with specific translocations
      as compared to sarcomas with complex genetics (p < 10(-9)). No difference was
      found for XPD. Genotyping of the tumor samples in synovial sarcomas and myxoid
      liposarcomas revealed frequent loss of heterozygosity for XPG, mostly due to the
      loss of the frequent allele. For XPD, both alleles were lost with a similar
      frequency. Our results raise the potential implication of the XPG Asp1104His
      polymorphism in the occurrence of chromosomal translocations associated with
      specific subtypes of sarcomas.

PMID- 16646070
TI  - Time to clearance of human papillomavirus infection by type and human
      immunodeficiency virus serostatus.
AB  - Persistent infection with high-risk human papillomavirus (HPV) is central to
      cervical carcinogenesis. Certain high-risk types, such as HPV16, may be more
      persistent than other HPV types, and type-specific HPV persistence may differ by
      HIV serostatus. This study evaluated the association between HPV type and
      clearance of HPV infections in 522 HIV-seropositive and 279 HIV-seronegative
      participants in the HIV Epidemiology Research Study (HERS, United States, 1993
      2000). Type-specific HPV infections were detected using MY09/MY11/HMB01-based PCR
      and 26 HPV type-specific probes. The estimated duration of type-specific
      infections was measured from the first HPV-positive visit to the first of two
      consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals
      (CIs) for HPV clearance were calculated using Cox models adjusted for study site
      and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections
      were detected in 801 women with 4.4 years median follow-up. HRs for clearance of
      HPV16 and related types versus low-risk HPV types were 0.79 (95% CI: 0.64-0.97)
      in HIV-positive women and 0.86 (95% CI: 0.59-1.27) in HIV-negative women. HRs for
      HPV18 versus low-risk types were 0.80 (95% CI: 0.56-1.16) and 0.57 (95% CI: 0.22
      1.45) for HIV-positive and -negative women, respectively. HPV types within the
      high-risk category had low estimated clearance rates relative to low-risk types,
      but HRs were not substantially modified by HIV serostatus.

PMID- 16646071
TI  - Accuracy of epidermal growth factor receptor mutation analysis on the basis of
      small biopsy specimens in patients with nonsmall cell lung cancer.

PMID- 16646072
TI  - ARLTS1 variants and melanoma risk.
AB  - Variants in the tumor suppressor gene ARLTS1 (ADP-ribosylation factor-like tumor
      suppressor gene 1) have been shown to influence familial cancer risk. Both
      Cys148Arg and Trp149Stop were associated with an increased risk of familial or
      high-risk familial breast cancer, respectively. We studied the impact of these
      gene variants on melanoma risk, investigating 351 melanoma patients and 804
      control subjects. While ARLTS1 Trp149Stop did not influence melanoma risk (OR =
      0.83, 95% CI = 0.37-1.88, p = 0.65), Cys148Arg revealed a statistically
      significant association with an increased risk for heterozygous carriers (OR =
      1.43, 95% CI = 1.05-1.95, p = 0.02). An additional risk enhancement, though
      statistically non-significant, was observed in individuals with multiple
      melanomas (OR = 2.33, 95% CI = 0.87-6.26, p = 0.08).

PMID- 16646073
TI  - Risk factors for prostate cancer: A national case-control study.
AB  - Statutory notification of cancer in New Zealand provided an opportunity to
      investigate risk factors for prostate cancer in a large national population-based
      case-control study. We analyzed data obtained from telephone interviews with 923
      cases and 1,224 controls. For inclusion in the study, all subjects had to have
      been married at some time. We found an increased risk of prostate cancer among
      those with a history of prostate cancer in first degree relatives (RR 2.6; 95%
      CI, 1.9-3.7) and an increased risk of prostate cancer with length of marriage
      among men married only once and still married at interview. For a consecutive
      subgroup of 550 cases and 819 controls, data on height and weight at age 20 and
      at 5 years before interview were collected. Men less than or equal to 1.7 m in
      height at age 20 years had a lower risk of prostate cancer than men taller at
      that age. There was no association between weight or body mass index and risk of
      prostate cancer.

PMID- 16646074
TI  - Multi-target fluorescence in situ hybridization in bladder washings for
      prediction of recurrent bladder cancer.
AB  - The objective of this study was to evaluate the diagnostic value of chromosomal
      analysis by fluorescence in situ hybridization (FISH) for predicting recurrence
      of urothelial carcinoma (UC) after transurethral resection. One hundred and
      thirty-eight patients (median age 68.5 years) with a history of UC were eligible
      for this prospective study. FISH was applied to cytospin specimens prepared from
      bladder washings taken during a negative control cystoscopy. The multi-target
      FISH test UroVysion (Abbott/Vysis) containing probes to the centromeres of
      chromosomes 3, 7, 17 and the 9p21 locus was used. UC recurrence was defined as a
      positive biopsy during follow-up. The median follow-up time was 19.2 (4-52)
      months. FISH was positive in 50 (36%) patients and negative in 88 (64%) patients.
      A recurrence occurred in 39% of the patients with a positive FISH test and in 21%
      of patients with a negative FISH test. FISH positivity according to
      manufacturer's criteria, at the time of a negative cystoscopy, was not
      significantly associated with the risk of recurrence (p = 0.12). However, the
      sensitivity of the FISH test to predict recurrence was significantly improved by
      considering specimens with rare (< or =10) tetraploid cells as negative (p <
      0.006). In addition, presence of 9p21 deletion was significantly associated with
      recurrence (p < 0.01). Notably, positive standard cytology was an independent
      factor for subsequent recurrence in this study (p < 0.001). Taken together, multi
      target FISH may help to stratify the risk of recurrence of UC at the time of a
      negative follow-up cystoscopy. Defining the optimal threshold for FISH positivity
      requires consideration of tetraploid pattern and 9p21 deletion. Our results also
      emphasize the paramount importance of conventional cytology for UC surveillance.

PMID- 16646075
TI  - Benign ovarian cysts and breast cancer risk.
AB  - Benign ovarian cysts have been suggested to influence breast cancer risk. To
      provide a comprehensive picture of the relation between ovarian cysts and breast
      cancer, we analyzed the data of 3 case-control studies conducted in northern
      Italy and the Swiss Canton of Vaud between 1983 and 2001. These studies included
      6,315 incident, histologically confirmed breast cancer cases and 6,038 hospital
      based controls. Odds ratios (OR) and the corresponding 95% confidence intervals
      (CI) were estimated using unconditional multiple logistic regression models,
      including terms for sociodemographic, menstrual and reproductive factors.
      Overall, 4.9% of breast cancer cases and 6.6% of controls reported a history of
      ovarian cysts, with a multivariate OR of 0.72 (95% CI 0.62-0.85). The inverse
      association between ovarian cysts and breast cancer was consistent in separate
      strata of age at menarche, parity, age at menopause status and family history of
      breast cancer. No meaningful differences were also found across strata of
      menstrual cycle length, oral contraceptive use, history of oophorectomy and body
      mass index. Thus, the inverse relation between ovarian cysts and breast cancer
      risk was not accounted for by earlier menopause, or by any difference in
      reproductive and menstrual characteristics. Although some hormonal correlates of
      ovarian cysts may have a role on breast cancer risk, a biological explanation of
      this inverse association is still unclear.

PMID- 16646076
TI  - 2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing
      tumors by suppressing matrix metalloproteinase-9.
AB  - Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is
      identical with an angiogenic factor, platelet-derived endothelial cell growth
      factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated
      by TP activity, has been suggested to be a downstream mediator of TP function. 2
      Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of
      angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that
      nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival
      times than those injected with control KB/CV cells. KB/TP tumors were also more
      highly invasive than KB/CV tumors in mice. The expression levels of matrix
      metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in
      KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of
      KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors.
      Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells,
      and the invasive activity of the cells. L-dRib may be useful for the suppression
      of invasion of TP-expressing tumor cells.

PMID- 16646077
TI  - Clinically tolerable concentrations of arsenic trioxide induce p53-independent
      cell death and repress NF-kappa B activation in Ewing sarcoma cells.
AB  - Ewing sarcoma (ES), a highly malignant pediatric tumor, is consistently
      associated with translocations that fuse the EWS gene with a member of the ETS
      family gene, most commonly FLI-1. Despite significant advances with multiagent
      chemotherapy, surgery and radiotherapy, about 40% of ES patients still die from
      the disease. It is therefore necessary to explore novel agents for possible
      treatment of this tumor. Here the authors investigated the sensitivity of ES
      cells to clinically tolerable concentrations of arsenic trioxide (As2O3), a
      compound known to induce differentiation and apoptosis of other types of
      malignant cells. The authors report that As2O3 uniformly induced death of 6 ES
      derived cell lines irrespective of their p53 status. As2O3 resulted in an
      apoptotic phenotype which was inhibited by the broad-spectrum caspase inhibitor
      ZVAD-fmk. These effects correlated with prolonged c-jun N-terminal kinase
      activation, which is a signal for apoptosis in ES cells. As2O3 also decreased
      basal and cytokine-induced NF-kappa B activity. Since the authors previously
      demonstrated that NF-kappa B exerts an antiapoptotic action in ES cells, As2O3
      treatment may also result in a sensitization of these cells to other drugs used
      in combination therapy. These effects, combined with its antiangiogenic action,
      define As2O3 as a good candidate for future protocols to improve treatments of
      Ewing sarcomas, irrespective of the p53 status of the tumor.

PMID- 16646078
TI  - CD8 T-cell recognition of human 5T4 oncofetal antigen.
AB  - The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas,
      including colorectal, ovarian and gastric carcinomas. The restricted expression
      of 5T4 on tumor tissues as well as its implication in tumor progression and bad
      prognosis makes 5T4 a promising new candidate for immunotherapy. An MVA vaccine
      encoding 5T4 antigen has been successfully evaluated in preclinical studies in a
      murine tumor model. Here, we report the generation of human CD8 T cells specific
      for the 5T4 antigen by stimulation with autologous monocyte derived DC infected
      with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4). Analysis
      of several donors confirms a repertoire of such CD8 responses. In a parallel
      approach, incorporating the results of proteasome-mediated digestion of 5T4
      derived 35-mer peptides and the potential high affinity epitopes predicted by a
      computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC
      class I epitopes of 5T4 antigen. Two of these generated specific CD8 T cells
      after restimulation with peptide loaded autologous DC and assay by cytotoxicity
      and IFN gamma ELISPOT. Moreover these particular peptide generated T cells
      recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201
      as judged by IFN gamma ELISPOT or ELISA. Also, HLA-A*0201 CD8 T cells recognized
      these peptides in a DC-Ad5T4 polyclonal response. In conclusion, there is a
      repertoire of CD8 T cell recognition of 5T4 in normal human donors and some
      candidate HLA-A*0201 epitopes have been identified.

PMID- 16646079
TI  - Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to V alpha
      24+ NKT cell-mediated cytotoxicity.
AB  - There is an increasing awareness of the therapeutic potential for combining
      immune-based therapies with chemotherapy in the treatment of malignant diseases,
      but few published studies evaluate possible cytotoxic synergies between
      chemotherapy and cytotoxic immune cells. Human V alpha 24+/V beta 11+ NKT cells
      are being evaluated for use in cell-based immunotherapy of malignancy because of
      their immune regulatory functions and potent cytotoxic potential. In this study,
      we evaluated the cytotoxicity of combinations of chemotherapy and NKT cells to
      determine whether there is a potential to combine these treatment modalities for
      human cancer therapy. The cytotoxicity of NKT cells was tested against solid
      tumor derived cell lines NCI-H358, DLD-1, HT-29, DU-145, TSU-Pr1 and MDA-MB231,
      with or without prior treatment of these target cells, with a range of
      chemotherapy agents. Low concentrations of chemotherapeutic agents led to
      sensitization of cell lines to NKT-mediated cytotoxicity, with the greatest
      effect being observed for prostate cancer cells. Synergistic cytotoxicity
      occurred in an NKT cell in a dose-dependent manner. Chemotherapy agents induced
      upregulation of cell surface TRAIL-R2 (DR5) and Fas (CD95) expression, increasing
      the capacity for NKT cells to recognize and kill via TRAIL- and FasL-mediated
      pathways. We conclude that administration of cytotoxic immune cells after
      chemotherapy may increase antitumor activities in comparison with the use of
      either treatment alone.

PMID- 16646080
TI  - Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus
      casei induces E7-specific antitumor effects in C57/BL6 mice.
AB  - The mounting of a specific immune response against the human papillomavirus type
      16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing
      cancer cells from the cervical mucosa. To induce a mucosal immune response by
      oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface
      of Lactobacillus casei by employing a novel display system in which the poly
      gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus
      subtilis (chungkookjang) was used as an anchoring motif. After surface expression
      of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and
      immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7.
      E7-specific serum IgG and mucosal IgA productions were enhanced after oral
      administration and significantly enhanced after boosting. Systemic and local
      cellular immunities were significantly increased after boosting, as shown by
      increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells
      [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN
      gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse
      tumor model, animals receiving orally administered L. casei-PgsA-E7 showed
      reduced tumor size and increased survival rate versus mice receiving control (L.
      casei-PgsA) immunization. These results collectively indicate that the oral
      administration of E7 displayed on lactobacillus induces cellular immunity and
      antitumor effects in mice.

PMID- 16646081
TI  - The major subtypes of human B-cell lymphomas lack mutations in BCL-2 family
      member BAD.
AB  - Members of the BCL-2 gene family are well known for their role in the
      pathogenesis of B-cell lymphomas in humans and in mouse models. A recent report
      that knockout mice deficient for the proapoptotic BCL-2 family member gene BAD
      frequently develop B-cell lymphomas prompted us to analyze a large collection of
      human B-cell lymphomas for inactivating mutations in the BAD gene. All 3 exons of
      the BAD gene were amplified and directly sequenced. The 81 lymphomas analyzed
      included 16 cases of B-cell chronic lymphocytic leukemia, 11 mantle-cell
      lymphomas, 10 follicular lymphomas, 7 MALT lymphomas, 8 Burkitt's lymphoma cell
      lines, 3 cell lines of multiple myeloma, 15 cases and 4 cell lines of diffuse
      large B-cell lymphoma and 7 Hodgkin's lymphoma lines. No mutations were found in
      any of the cases. We conclude that mutations in the BAD gene do not play a role
      in the pathogenesis of the major subtypes of human B-cell lymphomas.

PMID- 16646082
TI  - Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53
      proteins in prostate cancer cells.
AB  - The role of cyclooxygenase-2 (COX-2) and the mechanism by which it influences the
      development and behavior of prostate cancer is unclear. Selective COX-2
      inhibitors may be effective against prostate cancer via COX-2-independent
      mechanisms. But administration of high doses of COX-2 inhibitors over longer
      period of time may not be devoid of side effects. There is increasing interest in
      using COX-2 inhibitors in combination with other chemopreventive agents to
      overcome the issue of toxicity. However, the molecular mechanisms underlying
      their combined actions are not well understood. Therefore, the present study was
      designed to determine the effects of low doses of docosahexaenoic acid (DHA) in
      combination with celecoxib on the molecular targets at the proteins level in rat
      prostate cancer cells. Two-dimensional gel electrophoresis, in combination with
      mass spectrometry analysis, was used for protein identification. Western blot
      analysis confirmed the proteins identified. Paraffin-embedded tissue sections
      from the rat prostate tumor were used to detect base level expression of heat
      shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited
      more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses
      (2.5 microM each). A total number of twelve proteins were differentially
      expressed by the combined action of DHA and celecoxib at low doses. It was
      interesting to note that these agents activated both HSP70 and p53 proteins.
      Activation of HSP70 by the combined actions of DHA and celecoxib in the presence
      of wild-type p53 reveals a unique COX-2 independent mode of action against
      prostate cancer.

PMID- 16646083
TI  - A20 inhibits oxidized low-density lipoprotein-induced apoptosis through negative
      Fas/Fas ligand-dependent activation of caspase-8 and mitochondrial pathways in
      murine RAW264.7 macrophages.
AB  - A20 was originally characterized as a TNF-inducible gene in human umbilical vein
      endothelial cells. As an NF-kappaB target gene, A20 is also induced in many other
      cell types by a wide range of stimuli. Expression of A20 has been shown to
      protect from TNF-induced apoptosis and also functions via a negative-feedback
      loop to block NF-kappaB activation induced by TNF and other stimuli. To date,
      there are no reports on whether A20 can protect OxLDL-induced apoptosis in
      macrophages. For the first time we report that A20 expression blocks OxLDL
      mediated cell toxicity and apoptosis. OxLDL induced the expression of Fas and
      FasL, and the subsequent caspase-8 cleavage and treatment with a neutralizing ZB4
      anti-Fas antibody blocked apoptosis induced by OxLDL. Expression of dominant
      negative FADD efficiently prevented OxLDL-induced apoptosis and caspase-8
      activation. A20 expression significantly attenuated the increased expression of
      Fas and FasL, and Fas-mediated apoptosis. These findings suggest that A20
      mediated protection from OxLDL may occur at the level of Fas/FADD-caspase-8 and
      be FasL dependent. Treatment of RAW264.7 cells with OxLDL induces a series of
      time-dependent events, including the release of cytochrome c, Smac and Omi from
      the mitochondria to the cytosol, activation of caspase-9, -6, -2, and -3, which
      are blocked by A20 expression. No cleaved form of Bid was detected, even
      treatment with OxLDL for 48 h. Expression of dominant negative FADD also
      efficiently prevented OxLDL-induced the above apoptotic events. The release of
      cyto c, Smac and Omi from mitochondria to cytosol, activated by OxLDL treatment,
      and the activation of caspase-9 may not be a downstream event of caspase-8
      mediated Bid cleavage. Therefore, the protective effect of A20 on mitochondrial
      apoptotic pathway activated by OxLDL may be dependent on FADD. A20 expression
      reversed OxLDL-mediated G(0)/G(1) stage arrest by maintaining the expression of
      cyclin B1, cyclin D1, and cyclin E, and p21 and p73. Thus, A20 expression blocks
      OxLDL-mediated apoptosis in murine RAW264.7 macrophages through disrupting
      Fas/FasL-dependent activation of caspase-8 and the mitochondria pathway.

PMID- 16646084
TI  - Degradation of C/EBPbeta in cultured myotubes is calpain-dependent.
AB  - Members of the C/EBP transcription factor family regulate cell differentiation
      and multiple other cellular functions. The cellular levels of C/EBPalpha, gamma,
      delta, epsilon, and Gadd153/CHOP are regulated in part by proteasome-dependent
      degradation. In contrast, mechanisms regulating the degradation of C/EBPbeta are
      poorly understood. We tested the hypothesis that the degradation of C/EBPbeta is
      calpain-dependent. Studies were performed in cultured L6 myotubes (a rat skeletal
      muscle cell line) because we have found previously that C/EBPbeta may be involved
      in the regulation of muscle proteolysis. Treatment of cultured L6 myotubes with
      the calpain inhibitors calpeptin and Calpain Inhibitor I and II resulted in
      increased C/EBPbeta concentrations but did not influence cellular levels of the
      other C/EBP transcription factor family members. Transfection of myoblasts with a
      plasmid expressing the endogenous calpain inhibitor calpastatin resulted in
      increased cellular levels of C/EBPbeta whereas the opposite result was observed
      in myoblasts overexpressing micro- or m-calpain. Co-immunoprecipitation provided
      evidence for protein-protein interaction between C/EBPbeta and micro- and m
      calpain suggesting that C/EBPbeta may be a calpain substrate. This notion was
      supported by experiments in which immunoprecipitated C/EBPbeta was incubated with
      purified micro-calpain in a cell-free system. The increase in C/EBPbeta levels
      caused by inhibition of calpain activity was accompanied by increased C/EBPbeta
      DNA-binding and gene activation. The present results suggest that C/EBPbeta is
      degraded by a calpain-dependent mechanism in skeletal muscle cells and that the
      role of calpains is specific for C/EBPbeta among different members of the C/EBP
      transcription factor family.

PMID- 16646085
TI  - Human fibroblasts undergo oxidative stress-induced apoptosis without
      internucleosomal DNA fragmentation.
AB  - In order to evaluate the reliability of fibroblasts as a cell model for studying
      apoptosis, we tested the response of normal human fibroblasts to the oxidative
      stress inducers H(2)O(2) and 2-deoxy-D-ribose (dRib). Our results showed that
      fibroblasts treated with dRib and H(2)O(2) are induced to undergo apoptosis as
      demonstrated by reduction in total cell number, chromatin condensation,
      phosphatidylserine (PS) exposure, activation of caspase-3 and 7, changes in
      mitochondrial membrane potential and increase in the number of terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive
      nuclei. However we only found a slight increase in the percentage of cells in the
      sub-G1 region evaluated by flow cytometry, and we did not observe DNA
      fragmentation by agarose gel electrophoresis. Early in apoptosis, DNA cleavage
      generates high molecular weight (HMW) fragments which can be detected by TUNEL
      assay; successively followed by a pronounced DNA brake down into low molecular
      weight (LMW) fragments, detected as a "DNA ladder" by conventional agarose gel
      electrophoresis and as an hypodiploid peak by propidium iodide (PI) flow
      cytometry assay. Our results thus suggest that only HMW fragmentation occurs in
      fibroblasts exposed to dRib or H(2)O(2) and the lack of internucleosomal DNA
      fragmentation may depend on the peculiar characteristics of human fibroblasts
      themselves, irrespective of the apoptotic stimulus used. The existence of
      distinct events leading to cell death in different cell types makes it necessary
      to use a combination of strategies and techniques to evaluate the occurrence of
      apoptosis.

PMID- 16646086
TI  - High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a
      dismal outcome and ectopic expression of HLXB9.
AB  - The t(7;12)(q36;p13) is a recurrent translocation involving the ETV6/TEL gene
      (12p13) and a heterogeneous breakpoint at 7q36. A fusion transcript between HLXB9
      and ETV6 in AML with t(7;12) is occasionally found. To study the incidence of
      t(7;12) in infant and childhood acute leukemia, we screened 320 cases <36 months
      using FISH. Additionally, 28 pediatric cases >36 months with cytogenetic
      breakpoints at 12p and 7q were investigated. We studied the presence of an HXLB9
      ETV6 fusion transcript and quantified the expression of various genes located in
      the 7q36 breakpoint region. In total, six AML patients carried the t(7;12) of
      which five were infants and one child of 18 months. Only one out of 99 infant ALL
      patients harbored the t(7;12). No t(7;12) was found in older children with AML or
      ALL. AML patients carrying a t(7;12) had a poor outcome with a 3-year EFS of 0%.
      A fusion of HLXB9 to ETV6 was found in four AML cases with t(7;12). The 7q36
      genes NOM1, LMBR1, RNF32, and SHH were equally expressed among t(7;12)-positive
      AML versus t(7;12)-negative AML, t(7;12)-negative ALL, or normal bone marrow.
      However, the HLXB9 expression was highly increased in t(7;12)-positive cases,
      including those with an HLXB9-ETV6 fusion. We conclude that the t(7;12) is almost
      exclusively present in infant AML and covers 30% of infant AML, while it is
      extremely rare in infant ALL and older children. The t(7;12) is associated with a
      poor outcome and an ectopic expression of HLXB9 is commonly involved in this
      genetic subtype of leukemia.

PMID- 16646087
TI  - Ionizing radiation enhances adenoviral vector expressing mda-7/IL-24-mediated
      apoptosis in human ovarian cancer.
AB  - Ovarian cancer is the fifth most common cause of cancer-related death in women.
      Current interventional approaches, including debulking surgery, chemotherapy,
      and/or radiation have proven minimally effective in preventing the recurrence
      and/or mortality associated with this malignancy. Subtraction hybridization
      applied to terminally differentiating human melanoma cells identified melanoma
      differentiation associated gene-7/interleukin-24 (mda-7/IL-24), whose unique
      properties include the ability to selectively induce growth suppression,
      apoptosis, and radiosensitization in diverse cancer cells, without causing any
      harmful effects in normal cells. Previously, it has been shown that adenovirus
      mediated mda-7/IL-24 therapy (Ad.mda-7) induces apoptosis in ovarian cancer
      cells, however, the apoptosis induction was relatively low. We now document that
      apoptosis can be enhanced by treating ovarian cancer cells with ionizing
      radiation (IR) in combination with Ad.mda-7. Additionally, we demonstrate that
      mda-7/IL-24 gene delivery, under the control of a minimal promoter region of
      progression elevated gene-3 (PEG-3), which functions selectively in diverse
      cancer cells with minimal activity in normal cells, displays a selective
      radiosensitization effect in ovarian cancer cells. The present studies support
      the use of IR in combination with mda-7/IL-24 as a means of augmenting the
      therapeutic benefit of this gene in ovarian cancer, particularly in the context
      of tumors displaying resistance to radiation therapy.

PMID- 16646088
TI  - Effect of arachidonic and eicosapentaenoic acid metabolism on RAW 264.7
      macrophage proliferation.
AB  - Prostaglandins (PGs) and leukotrienes (LTs) derived from arachidonic acid (AA)
      are potent mediators of inflammation and cell proliferation. Dietary intake of
      eicosapentaenoic acid (EPA) appears beneficial to both inflammatory processes and
      cell proliferation. However, there is no clear mechanism explaining these
      effects. In this study, we investigated the effect of EPA on the AA incorporation
      in phospholipid membranes, on AA release and metabolism, and consequently, on PG
      synthesis. Our results showed not only that [(3)H]AA and [(14)C]EPA were similar
      incorporated into RAW 264.7 macrophage membranes, but also that the
      redistribution pattern between phospholipids was alike. [(3)H]AA or [(14)C]EPA
      release was induced by fetal bovine serum (FBS) in a similar fashion with AA
      metabolizing 3-fold more than EPA. In this way, we observed that AA could be
      metabolized by cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase (5-LOX) whereas
      EPA was metabolized by COX-2 and 5-LOX pathways. Moreover, both fatty acids were
      able to induce COX-2 expression. When we incubated [(3)H]AA labeled cells with
      exogenous EPA, we observed that EPA did not modify FBS-induced [(3)H]AA release
      but that the presence of EPA decreased [(3)H]AA metabolism and therefore PGE(2)
      synthesis. Moreover, we studied the effect of AA and EPA metabolites on
      macrophage proliferation. Our results showed that PGE(3) stimulated cell growth
      with a potency similar to that of PGE(2), whereas LTB(5) was less effective than
      LTB(4). These data suggest that the effects of EPA on cell growth might be
      attributable, at least in part, to the marked decrease of eicosanoid release.

PMID- 16646089
TI  - Neuronal control of the cardiac responses to osmotic stress in the gastropod
      limpet Patella caerulea.
AB  - Mediterranean limpets Patella caerulea were exposed to different salinity
      conditions and treated with drugs interfering with neuronal control of heartbeat.
      Heart rate was monitored using a non-invasive method. Limpets were superfused
      with control (33 g l(-1)), hyposaline (0 and 10 g l(-1)) or hypersaline (56 and
      66 g l(-1)) artificial seawater. Under osmotic stress the limpets showed an
      initial increase of heart rate, followed by acardia, particularly under
      hyposalinity. The tachycardia observed after exposure to 56 g l(-1) was abolished
      in the animals injected with a selective sodium channel blocker, tetrodotoxin
      (TTX), or with a serotoninergic antagonist, methysergide. Injection of TTX also
      partly prevented the acardia occurring at 0 g l(-1). The acardia was completely
      prevented after injection with atropine and benzoquinonium, two selective
      cholinergic antagonists. These findings indicate that cardiac responses of P.
      caerulea to variations in external salinity are regulated by an extrinsic
      neuronal control involving the serotoninergic and the cholinergic systems in the
      tachycardic and acardic responses, respectively.

PMID- 16646090
TI  - LacO-LacI interaction in affinity adsorption of plasmid DNA.
AB  - Current approaches for purifying plasmids from bacterial production systems
      exploit the physiochemical properties of nucleic acids in non-specific capture
      systems. In this study, an affinity system for plasmid DNA (pDNA) purification
      has been developed utilizing the interaction between the lac operon (lacO)
      sequence contained in the pDNA and a 64mer synthetic peptide representing the DNA
      binding domain of the lac repressor protein, LacI. Two plasmids were evaluated,
      the native pUC19 and pUC19 with dual lacO3/lacOs operators (pUC19(lacO3/lacOs)),
      where the lacOs operator is perfectly symmetrical. The DNA-protein affinity
      interaction was evaluated by surface plasmon resonance using a Biacore system.
      The affinity capture of DNA in a chromatography system was evaluated using LacI
      peptide that had been immobilized to Streamline adsorbent. The KD-values for
      double stranded DNA (dsDNA) fragments containing lacO1 and lacO3 and lacOS and
      lacO3 were 5.7 +/- 0.3 x 10(-11) M and 4.1 +/- 0.2 x 10(-11) M respectively,
      which compare favorably with literature reports of 5 x 10(-10)-1 x 10(-9) M for
      native lacO1 and 1-1.2 x 10(-10) M for lacO1 in a saline buffer. Densitometric
      analysis of the gel bands from the affinity chromatography run clearly showed a
      significant preference for capture of the supercoiled fraction from the feed pDNA
      sample. The results indicate the feasibility of the affinity approach for pDNA
      capture and purification using native protein-DNA interaction.

PMID- 16646091
TI  - Optical switching of self-assembly: micellization and micelle-hollow-sphere
      transition of hydrogen-bonded polymers.

PMID- 16646092
TI  - Fluorescent quantum dots with boronic acid substituted viologens to sense glucose
      in aqueous solution.

PMID- 16646093
TI  - Cyclophanes within cyclophanes: the synthesis of a pyromellitic diimide-based
      macrocycle as a structural unit in a molecular tube and its inclusion phenomena.

PMID- 16646094
TI  - Total synthesis of (+)-machaeriol D with a key regio- and stereoselective S(N)2'
      reaction.

PMID- 16646095
TI  - Platinum-functionalized octahedral silica nanocages: synthesis and
      characterization.

PMID- 16646096
TI  - Copper-catalyzed preparation of ketones bearing a stereogenic center in alpha
      position.

PMID- 16646097
TI  - Ultrahigh resolution in proton solid-state NMR spectroscopy at high levels of
      deuteration.

PMID- 16646098
TI  - Surface plasmon resonances of free-standing gold nanowires fabricated by
      nanoskiving.

PMID- 16646099
TI  - Designed CO2-philes stabilize water-in-carbon dioxide microemulsions.

PMID- 16646100
TI  - Orthogonal glycosylation reactions on solid phase and synthesis of a library
      consisting of a complete set of fucosyl galactose isomers.

PMID- 16646101
TI  - Short synthesis of skeletally and stereochemically diverse small molecules by
      coupling petasis condensation reactions to cyclization reactions.

PMID- 16646102
TI  - Towards a general scale of nucleophilicity?

PMID- 16646103
TI  - High thermoelectric figure of merit and nanostructuring in bulk p-type Na1
      xPbmSbyTem+2.

PMID- 16646105
TI  - The puzzling properties of supercooled and glassy water.

PMID- 16646104
TI  - Organocatalytic conjugate addition of malonates to alpha,beta-unsaturated
      aldehydes: asymmetric formal synthesis of (-)-paroxetine, chiral lactams, and
      lactones.

PMID- 16646106
TI  - [Munchner screening of auditory perception disorders (MAUS)].
AB  - BACKGROUND: The diagnosis of APD (Auditory Perception Disorder) is a time
      consuming procedure. In Germany at the present, no screening test for APD exists
      which makes it possible to differentiate between children who are not likely to
      suffer from an APD and those who need to be diagnosed in detail. METHOD: The
      Munich Auditory Screening of Perception Disorders (MAUS) contains the following
      subtests: Series of Syllables, Words in Noise and Identification and
      Differentiation of Phonemes (test duration: 15 minutes). PATIENTS: The MAUS was
      standardized using 359 primary school children between 6 and 11 years of age.
      Furthermore, the MAUS was used in addition to the complete, extensive APD
      diagnostics in testing 52 children (36 with APD and 16 without APD) within the
      age group mentioned. RESULTS: T-scores for each subtest were established by the
      standardization of the MAUS. The internal consistency of the test was sufficient.
      The intercorrelation between subtests was very slight. Therefore, each subtest
      seems to play an independent part in defining the construct of APD. Because of
      the results of the pilot study which formed the basis for the development of the
      screening instrument used, and because of the sensitivity scores reached in
      testing a group of 36 children with diagnosed APD, it can be expected that the
      MAUS will show a high sensitivity with regard to APD. CONCLUSION: Using the MAUS,
      it can be determined if and to what extent the test results of an individual
      deviate from those of the normal primary school population. The MAUS can identify
      children at risk of having an APD and can differentiate these children from those
      who are unlikely to suffer from an APD.

PMID- 16646107
TI  - [Ethisorb/Ethisorb durapatch for the transnasal duraplasty procedure?].
AB  - BACKGROUND: Defects of the dura in the rhinobasal area can be closed
      transnasally. Various procedures with autologous or alloplastic material can be
      chosen. METHOD: From 2001 to 2004, we closed a rhinobasal dura defect with
      Ethisorb or Ethisorb durapatch in sandwich technique in 8 patients. After
      smoothing the bone edges, Ethisorb is applied under microscopic or endoscopic
      view endocranially, extradurally as "underlay" to seal and absorb the liquor
      pressure pillar. Additionally, another Ethisorb implant as "underlay" is applied
      extracranially from endonasally as "underlay", and sealed with a further layer of
      nasal concha mucosa with fibrin glue. RESULTS: All patients were successfully
      treated with this technique. There were no evidences for persisting
      rhinoliquorrhoe after the period of wound healing. For hemostasia, a nasal
      package was applied for compression at the donor site of the inferior nasal
      concha. The former dura defect was at all times freely accessible in order to be
      able to recognize a possible new rhinoliquorrhoea early and to prevent a possible
      congestive secretion with superinfection. DISCUSSION: The material of Ethisorb
      and Ethisorb durapatch is stiff and can be easily modelled, so it is an
      alternative as an alloplastic material for endonasal closure of defined
      substantial defects of the dura with rhinoliquorrhoe.

PMID- 16646108
TI  - [Multidisciplinary management of skull base and craniocervical chordoma].
AB  - BACKGROUND: Craniocervical chordomas often only become manifest in an advanced
      stage. The localisation and locally-destructive growth require a
      multidisciplinary diagnostic and therapeutic concept early on. The goal of the
      present study was to present a reproducible strategy for quality assurance.
      PATIENTS AND METHOD: We retrospectively analysed the hospital records of 10
      consecutive patients (4 women and 6 men) whom we had treated during a period of 7
      years. RESULTS: The first step in therapy was tumour resection in 9 cases. One
      patient initially underwent stereotactic radiation. Postoperative radiation was
      not included a priori, but discussed individually depending on the degree of
      resection, the patient's age and physical condition. After an average 5 years
      follow up, 100 % of patients are alive. In all patients, tumour control was
      achieved. CONCLUSIONS: The prognosis for patients with chordomas of the skull
      base has improved considerably in recent years. New technologies like
      intraoperative navigation and improved radiation procedures have contributed to
      this improvement. The basis for treatment remains, however, the greatest possible
      surgical exstirpation with minimal surgical morbidity. Special attention should
      be paid in this connection to the stability of the cervical spine and the
      craniocervical transition border. In advanced tumour growth, complete resection
      is often not possible. Proton and heavy-ion radiation are promising new forms of
      therapy, which can also be applied after conventional radiation has been
      performed. A directed multidisciplinary procedure guarantees years of survival
      with good quality of life in many cases.

PMID- 16646109
TI  - [Chromosome 1q syndrome and hearing loss: an unusual case].
AB  - INTRODUCTION: The interstitial deletion of chromosome 1q is a disease of rare
      incidence, which might be hereditary or caused by spontaneous changes within the
      chromosome respectively. The phenotype in most cases is based on the loss of
      macrochromosomal material within the long arm of chromosome 1. The
      characteristics of this syndrome include pre- and postnatal growth retardation,
      severe psychomotor retardation, microbrachycephaly, sparse fine scalp hair and
      eyebrows, deformity of skull with cleft of lips and palate, scoliosis, small
      hands and feet hernias, genital defects, clinodactyly of the fifth fingers and
      campylodactyly. Other morphological characteristics that have been reported are
      mainly kidney and cardiac abnormalities. The number of symptoms are related to
      the loss of genetic material. To our knowledge this is the first description of a
      patient with interstitial deletion of chromosome 1 (q23-q31). PATIENT: We report
      an eleven year old boy with interstitial deletion of chromosome 1(q23-q31). In
      addition to the known skeletal, orofacial disorders, hypothrophia and retardation
      we discovered a unilateral high-graded and contralateral middle-graded hearing
      loss. CONCLUSION: In infants with chromosome 1q syndrome adequate diagnostic
      procedures have to be employed to unveil sensineural hearing losses that might be
      overseen because of mental retardation. In particular a brainstem electric
      response audiometry should be considered for early diagnosis and treatment of a
      possible hearing-loss.

PMID- 16646110
TI  - [Cutaneous form of sarcoidosis at the auricle].
AB  - Sarkoidosis is a disease of so far unknown etiology that can affect potentially
      every organ. Sarcoidosis of the lung is the most common form, nevertheless in
      more than one third of the cases the head and neck area is affected.
      Manifestations of the disease can be present in lymph nodes of the neck, the
      middle ear, the pars petrosa of the temporal bone and in the paranasal sinuses as
      well as in the larynx and pharynx. We would like to present two rare
      manifestations of sarkoidosis of the ear lobe. The cutaneous form of sarcoidosis
      is characterized by a spectrum of skin changes. Aside from the physical
      presentation and observation of the disease progress the diagnosis is confirmed
      histologically. A multidisciplinary care of the affected patients is needed to
      diagnose the systemic extend of the disease on one side and to provide the
      patient with an effective therapeutic regimen that includes surgical and
      conservative measures on the other.

PMID- 16646111
TI  - [Clarification of alternative methods of therapy before operating a neck tumor of
      not clarified dimension].

PMID- 16646112
TI  - Parity for federal workers improves insurance protection with little adverse
      effect on total costs.

PMID- 16646114
TI  - Abstracts of the Annual Main Meeting of the Society for Experimental Biology, 2-7
      April 2006, Canterbury, United Kingdom.

PMID- 16646113
TI  - NAMI publishes report cards on state public mental health systems.

PMID- 16646115
TI  - Neuropsychological correlates of impaired emotion recognition  following
      traumatic brain injury.
AB  - Previous research has shown that individuals with traumatic brain injury (TBI)
      are significantly impaired on emotion recognition tasks. In this study, the
      relationship between neuropsychological functioning and emotion recognition was
      examined in 11 individuals with moderate to severe TBI and a control group of 13
      individuals matched for age,sex, and education. Emotion recognition stimuli were
      from Ekman and Friesen's pictures of facial affect. The group with TBI showed
      neuropsychological deficits consistent with those commonly found following
      moderate to severe TBI. The group with TBI also identified significantly fewer
      emotion recognition stimuli than the control group. The number of correctly
      identified emotion recognition stimuli was significantly correlated with measures
      of verbal cognitive processing in the group with TBI. These findings suggest that
      the role of left hemisphere brain mechanisms in the recognition of facial
      (nonverbal)emotion may be more important than previously recognized.

PMID- 16646116
TI  - Emotional and pain-related factors in neuropsychological  assessment following
      mild traumatic brain injury.
AB  - A critical issue in the field of clinical neuropsychology is the idea that
      emotional or pain-related factors may compromise the validity of
      neuropsychological assessment. In this study, 53 individuals suffering from mild
      traumatic brain injury related to motor vehicle accident injury completed
      commonly used measures of emotional and pain-related functioning. A battery of
      commonly used neuropsychological tests, assessing attention, learning and memory,
      language, visuospatial and visuomotor functions, speeded processing, fine-motor
      skill, and symptom validity, was administered concurrently. Findings revealed a
      significant and negative correlation between anxiety and impaired delayed verbal
      memory, suggesting that as anxiety increased, delayed verbal memory decreased.
      The results otherwise provided little support for the idea that emotional or pain
      related factors are detrimental to neuropsychological test performance following
      mild traumatic brain injury.

PMID- 16646117
TI  - Intact theory of mind in TBI with behavioural disturbance.
AB  - Behavioural disturbance following TBI is common. Theory of mind(ToM) deficits
      have been noted in autism where difficulties with social interaction and
      communication are evident. It was hypothesised that TBI patients with behavioural
      disturbance would show deficits on ToM tasks independent of executive function.
      Twenty TBI patients with behavioural disturbance and 20 TBI patients without were
      assessed on verbal (stories) and non-verbal (cartoons) ToM tasks,standard
      psychometry, and measures of executive function.TBI patients were unimpaired on
      the ToM tasks. Both groups were unimpaired on standard tests of executive
      function (verbal fluency and trail making test) but were impaired on the
      Behavioural Assessment of Dysexecutive Syndrome (BADS). Groups did not differ
      significantly on these tests. It is concluded that ToM ability does not predict
      behavioural disturbance and may be independent of executive functioning.

PMID- 16646118
TI  - Central executive system impairment in traumatic brain injury.
AB  - The aim of the present study was to identify cognitive functions affected by
      traumatic brain injury (TBI) and to verify the mechanism underlying cognitive
      impairment. More precisely, cognitive deficits following TBI can be considered as
      a consequence of (a) a speed processing deficit, that is a general slowing of
      perceptual, motor and cognitive subroutines; (b) an impairment of the Central
      Executive System of working memory (CES).Thirty-seven patients were submitted to
      a neuropsychological battery, aimed to evaluate different cognitive functions.
      Results showed severe deficits in speed processing, divided attention,working
      memory, executive functions and long term memory. Regression analyses, performed
      to test the two hypotheses, showed that the working memory deficit hypothesis is
      able to explain divided attention, executive functions and long term memory
      deficits more than speed processing hypothesis.

PMID- 16646119
TI  - Is there a trade-off between cognitive and motor recovery after  traumatic brain
      injury due to competition for limited  neural resources?
AB  - The status of neurorehabilitation for traumatic brain injury (TBI) is under
      active debate because of a dearth of research findings demonstrating
      effectiveness. This may be due, in part, to limitations in our understanding of
      basic mechanisms of cognitive and motor recovery,including those that might
      impede recovery. In this regard, we examined whether overall recovery following
      TBI might be undermined by competition between cognitive and motor functions for
      finite neural resources during recovery. In this preliminary study, 21 moderately
      and severely impaired patients were administered cognitive and motor assessments
      at 1, 4, and 12 months post-TBI, and recovery of cognitive and motor functions
      was measured using regression residuals. Negative correlations between recovery
      of cognitive versus motor functions were used as the index of competition. We
      found suggestive evidence that there may indeed be a trade-off between the
      recovery of cognitive and motor functions after TBI. Implications for
      rehabilitation are discussed.

PMID- 16646120
TI  - Evidence of transient enhancement to cognitive functioning in healthy young
      adults through environmental enrichment: implications for rehabilitation after
      brain injury.
AB  - We examined preliminarily whether intensive mental activity can transiently
      enhance higher cognitive functioning in healthy adults. Ten healthy participants
      performed intensive mental activity for 2 weeks. The intervention entailed daily
      memorization of multiple prose passages and performance of demanding, speeded
      mental arithmetic.Neuropsychological testing was conducted before and after the
      intervention, using alternate forms. (The intervention and neuropsychological
      tests were different.) Findings in the intervention group were compared to those
      of a convenience control sample who had performed a near-identical
      neuropsychological assessment and follow-up in a different study, but who did not
      perform the intervention. The purpose was to rule out practice effects as the
      cause of any observed improvement in the intervention group. The intervention
      group showed improvement on six/eight measures. The non-intervention group showed
      improvement on only two. Results suggest cognitive capacity can be enhanced in
      healthy individuals after a period of intensive cognitive stimulation.
      Implications for rehabilitation are discussed.

PMID- 16646121
TI  - Improving treatment response of cognitively impaired veterans with 
      neuropsychological rehabilitation.
AB  - This pilot study examined the effect of computerized neuropsychological
      rehabilitation (NR) on cognitively impaired veterans' behavior while in treatment
      for polysubstance abuse. A group of 10 veterans participated in a 10-session
      adjunctive program of NR. This group was rated for length of stay in treatment
      and behavioral change and participation in treatment. Comparisons were made with
      a group of nine veterans who were in the standard substance abuse treatment with
      no adjunctive NR. Mild to moderate neuropsychological impairments were present in
      both groups in the areas of immediate and delayed memory, prospective memory,
      problem solving, and visual scanning and tracking. Relative to controls, the
      group that participated in NR was found to remain in treatment significantly
      longer and rated as having a better overall attitude in the general treatment
      program. These data suggest that NR may have positive treatment implications in
      patients with mild to moderate neuropsychological impairment.

PMID- 16646122
TI  - Long-term outcomes of pediatric acquired brain injury.
AB  - Recent studies have shown that persisting deficits remain even in young children
      with mild brain injuries. Our 2-year study investigated patterns of recovery in
      children and adolescents with ABI over the past 10 years. In the first year, we
      retrospectively reviewed demographic information (e.g., age at injury,
      gender,severity, GCS, coma length, and LOS), medical status, academic and therapy
      interventions, psychological, emotional and cognitive,physical, social, and
      family issues reported by parents and clients and outcome data from an adapted
      version of the Mayo-Portland Adaptability Inventory. In the second year of the
      study, we prospectively collected in-depth information through the use of new
      outcome measures, questionnaires and structured interviews. We focused on the
      relationships between persisting limitations (academic performance, pragmatic
      communication, social interactions, and physical abilities) and restrictions on
      participation (i.e., school, social relationships, vocational,and quality of
      life) of children who are between 3 and 5 years post-injury.

PMID- 16646123
TI  - Sexual offenses and traumatic brain injury.
AB  - A sample of 476 male sexual offenders, seen at a university psychiatric hospital
      for forensic assessment, was examined for the incidence of traumatic head
      injuries. A total of 49.3% had sustained head injuries that led to
      unconsciousness and of these 22.5% sustained significant neurological insults. A
      major causative factor was motor vehicle accidents, but lifestyle variables
      including alcohol and drug abuse and history of violence also contributed. The
      brain-injured group was convicted for a wide range of sexual offenses and was
      comparable to the non-injured group in this respect, but tended more often to
      offend against adults than against children and to show somewhat more exhibiting
      and polymorphous sexual behavior. In spite of the serious legal implications for
      these men and the additional distress to their families, psychologists,
      psychiatrists, and the professional literature have been relatively silent on the
      subject which calls for more attention to sexual behavior as part of assessments
      and treatment planning.

PMID- 16646124
TI  - Impairment and recovery in inhibitory control after traumatic brain injury in
      children: effect of age at injury, injury severity and lesion location.
AB  - We examined the effect of traumatic brain injury (TBI) on inhibitory control,
      trajectories of recovery of inhibitory control, and the effect of age at injury,
      severity, and lesion location on recovery. Participants were 127 children with
      TBI aged 5-16 years and 117 controls of similar age. Latency of response
      inhibition was measured with the stop signal task within 1 month of the injury
      and again at 3, 6, 12, and 24 months. Performance of children with TBI was
      compared with that of controls. Growth curve analyses showed impairments in
      response inhibition postinjury. Compared with controls, TBI children improved
      over time in response inhibition. Younger TBI children recovered better on
      response inhibition than older TBI children. No significant effect of severity or
      right frontal lesion on recovery of response inhibition was found. TBI has an
      acute effect on inhibitory control but which recovers over time.

PMID- 16646125
TI  - Natural history of the long-term cognitive, affective, and physical  sequelae of
      mild traumatic brain injury.
AB  - Mild traumatic brain injury (MTBI) is associated with cognitive,affective, and
      physical sequelae. When symptoms persist for more than 3 months, a diagnosis of
      Post-Concussion Syndrome (PCS) is often given. The current study tracked symptom
      development to explore the natural sequelae of MTBI. Twenty-six MTBI patients
      received a comprehensive neuropsychological assessment at three intervals: within
      1 week, at 4 months and at 7 months post-concussion. Based on DSMIV criteria and
      clinical judgment, two external raters diagnosed five MTBI participants with PCS.
      Results suggested that aspects of cognitive functioning of the symptomatic MTBI
      (i.e., PCS) participants were different from matched normal control (NC)
      subjects, and from the 21 MTBI patients who were asymptomatic, at 4 months.
      Asymptomatic MTBI participants improved in overall level of functioning from 4 to
      7 months, but remained significantly different from NC participants in their
      reduced verbal fluency and working memory functioning.

PMID- 16646126
TI  - Viewing the functional consequences of traumatic brain injury  by using brain
      SPECT.
AB  - High-resolution brain SPECT is increasingly benefiting from improved image
      processing software and multiple complementary display capabilities. This enables
      detailed functional mapping of the disturbances in relative perfusion occurring
      after TBI. The patient population consisted of 26 cases (ages 8-61 years)between
      3 months and 6 years after traumatic brain injury.A very strong case can be made
      for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed
      evaluation of multiple functional consequences after TBI and is thus capable of
      supplementing the clinical evaluation and tailoring the therapeutic strategies
      needed. In so doing it also provides significant additional information beyond
      that available from MRI/CT. The critical factor for Brain SPECT's clinical
      relevance is a carefully designed technical protocol, including displays which
      should enable a comprehensive description of the patterns found, in a user
      friendly mode.

PMID- 16646127
TI  - A rehabilitative program for central executive deficits after  traumatic brain
      injury.
AB  - Deficits affecting Central Executive System (CES) of working memory (WM) are the
      main neuropsychological outcome after traumatic brain injury (TBI) and can also
      explain deficits in other domains, like divided attention, executive functions
      and long-term memory. For this reason we developed a rehabilitative program based
      on CES functions and we expected to find an improvement in WM as well as in those
      cognitive functions controlled by the CES. The experimental group was composed by
      9 TBIs, selected for WM deficits, whereas the control group was composed by 6
      TBIs, without WM deficits, but with speed processing deficits. All patients
      performed a cognitive training, based on PASAT (Gronwall & Wrightson, 1981)and
      two new versions of this task. The results showed in the experimental group an
      improvement in WM and in the cognitive functions controlled by the CES, whereas
      control patients did not show any improvement after the cognitive training.

PMID- 16646128
TI  - Changes in coping style following traumatic brain injury and their  relationship
      to productivity status.
AB  - The use of maladaptive coping strategies following traumatic brain injury (TBI)
      is known to be associated with increased depression and a lower productivity
      status. What is not known is whether coping behaviours change following TBI and
      if they do change whether these changes account for significant variance in
      outcome. Seventy-three significant others of TBI survivors were recruited at the
      time their friend/family member was injured and followed prospectively. They
      reported on their friend/family member's pre-injury and 6-month coping behaviours
      using the Coping with Health Injuries and Problems Scale. The use of emotional
      pre-occupation coping (p = .02) increased significantly and approached
      significance for distraction coping(p = .08). These changes in coping also
      accounted for significant variance (22%, p = .02) in productivity status over and
      above that accounted for by demographics and injury severity. Whether maladaptive
      coping changes can be prevented with a view to improving outcomes is a question
      that now needs to be explored.

PMID- 16646129
TI  - Diffusion tensor imaging for the evaluation of white matter  pathology in
      traumatic brain injury.

PMID- 16646130
TI  - Counterpoint: lactic acid accumulation is a disadvantage during muscle activity.

PMID- 16646131
TI  - "In health and in a normoxic environment, VO2 max is/is not limited primarily by
      cardiac output and locomotor muscle blood flow".

PMID- 16646132
TI  - "In health and in a normoxic environment, VO2 max is/is not limited primarily by
      cardiac output and locomotor muscle blood flow".

PMID- 16646133
TI  - "In health and in a normoxic environment, VO2 max is/is not limited primarily by
      cardiac output and locomotor muscle blood flow".

PMID- 16646134
TI  - "Supraspinal locomotor centers do/do not contribute significantly to the
      hyperpnea of dynamic exercise in humans".

PMID- 16646135
TI  - "Supraspinal locomotor centers do/do not contribute significantly to the
      hyperpnea of dynamic exercise in humans".

PMID- 16646136
TI  - "Supraspinal locomotor centers do/do not contribute significantly to the
      hyperpnea of dynamic exercise in humans".

PMID- 16646137
TI  - Morphologic quantification of heterogeneous parenchyma.

PMID- 16646138
TI  - Morphological quantitation of emphysema: a debate.

PMID- 16646139
TI  - Morphological quantitation of emphysema: a debate.

PMID- 16646140
TI  - Morphological quantitation of emphysema: a debate.

PMID- 16646141
TI  - Rx advances for advanced practice registered nurses.

PMID- 16646142
TI  - Alzheimer research forum live discussion: Imaging in Alzheimer's disease: the
      current state of affairs.

PMID- 16646143
TI  - Alzheimer research forum live discussion: Making a BioMark on Alzheimer disease.

PMID- 16646144
TI  - Bibliography. Current world literature. Seizure disorders.

PMID- 16646145
TI  - The ivied halls of industry.

PMID- 16646146
TI  - ["Bone-breaker fever" in paradise. Chikungunya fever raged on dreamy tropical
      islands before it did on the east coast of Africa].

PMID- 16646147
TI  - [The prelude to psychiatric reform in Brazil: the contradictions of the 1970s].
AB  - The article provides a historical reconstruction of the period leading up to what
      has become known as Brazil's Movement for Psychiatric Reform, which runs from the
      1967 creation of the national social welfare system (INPS) to 1978, when the
      Mental Health Workers Movement gained prominence. Focusing on technical criteria
      influenced by the U.S. prevention model, our discussion examines the
      contradictions in Brazil's official mental health policy and also looks at the
      practice of financing and strengthening private psychiatric institutions, to the
      detriment of community action. Although most official documents from the 1970s
      contain proposals clearly aimed at community actions, what we observe is the
      crystallization of a model under which the government purchases psychiatric beds
      in private hospitals.

PMID- 16646148
TI  - [Hunger, solidarity, and ethics: discourse analysis of the movement Citizen's
      Action against Hunger and Poverty and for Life].
AB  - The article analyzes the discourse of Citizen's Action against Hunger and Poverty
      and for Life, a social movement led by sociologist Herbert de Souza (Betinho)
      that was at its peak between 1993 and 1994. From the perspective of certain
      concepts and principles introduced and disseminated by so-called bio-ethics, the
      present study identifies within this campaign an attempt to construct a social
      movement in Brazil displaying characteristics quite similar to those associated
      with 'practical ethics'. These features are apparent in the three major
      principles that the movement applied as strategies for fighting hunger and
      poverty - to wit, solidarity, partnership, and decentralization.

PMID- 16646149
TI  - [The archeology of human aggressiveness: violence from a paleo-epidemiological
      perspective].
AB  - Acute traumatic injuries provide direct evidence that is used in studies of
      violence in the past. When analyzed from a paleo-epidemiological perspective and
      in conjunction with data from the material culture, these injuries are an
      important tool in the interpretation of human aggressive behavior. The latter,
      which seems to underlie human nature itself, has been recorded as far back as the
      remote time of man's ancestral hominids and in any type of social organization.
      By studying the pattern and distribution of blow marks and other signs of
      physical aggression, we contribute to our understanding not only of the
      emergence, use, motives, and impact of violence down through time but also of its
      continuance today.

PMID- 16646151
TI  - [Science as a network of actors: philosophical resonance].
AB  - The article analyzes what philosophical implications actor-network theory may
      have in studies of the sciences. Actor-network theory has revitalized the debate
      on the sciences because it puts the focus on investigating science in action,
      that is, on science as it is actually practiced in the research laboratory. The
      concepts of subject and object, along with the concepts of truth, rationality,
      and scientific facts, are redefined from the perspective of actor-network theory.
      The article analyzes possible alliances between this theory and the philosophy of
      difference proposed by Deleuze, Guattari, and Serres.

PMID- 16646152
TI  - [In the gap between science and art: a series of illustrations of triatomine bugs
      from the Oswaldo Cruz Institute].
AB  - The article analyzes a series of scientific drawings created and printed as part
      of a scientific work that has never been published out by the Oswaldo Cruz
      Institute. Deemed "incorrect" by scientists, these drawings lay abandoned for
      over seventy years. We have investigated their history in an effort to discover
      what might have led science to condemn the series. We also undertook a brief
      historical analysis of verisimilitude in scientific drawing. This case affords an
      interesting opportunity to explore some aspects of representation in artistic
      production, like issues involving vision, perception, the interpretation of
      images and visual communication through them, the functionality and objectivity
      of scientific illustration, as well as certain distinctions between the
      characteristics of illustration in zoology and in cartography and botany, and its
      ambiguous relationship with art.

PMID- 16646153
TI  - [History of public health in Mexico: 19th and 20th centuries].
AB  - During the nineteenth and twentieth centuries, its growth accompanied the
      country's political and social changes. In the early half of the nineteenth
      century, care for the sick depended in part on religious charity. So-called
      public beneficial care was later introduced and consolidated under president
      Benito Juarez (1856) and then continued under Porfirio Diaz (1880-1910). The
      Mexican Revolution (1910-1917) brought the notion that public-health assistance
      is the State's social responsibility. Health care and social security are now
      both part of so-called "institutional medicine," which also encompasses research
      and teaching on public health. This analysis of public-health care in Mexico
      examines the question of diseases and their control, the emergence of
      institutions, and the development of the concept of public health.

PMID- 16646154
TI  - [Parabolic parables: predictive genetic testing, social constructions of risk,
      and the relation between health-care professionals and the mass media].
AB  - The article examines conceptual topics underlying construction of the "new public
      health" and epidemiology, particularly its molecular branch and the idea of
      genetic risk, in the face of issues raised by new technologies, globalization,
      today's vast increase in communication strategies, and the weakening of identity
      links. Problems related to the creation of new interdisciplinary fields are also
      considered, such as epidemiology and molecular genetics. The repercussions of the
      social communication of genetic contents (especially predictive genetic testing
      and the cloning of mammals) are also analyzed.

PMID- 16646155
TI  - Glutamate release from astrocytes as a non-synaptic mechanism for neuronal
      synchronization in the hippocampus.
AB  - Synchronization of activity of anatomically distributed groups of neurons
      represents a fundamental event in the processing of information in the brain.
      While this phenomenon is believed to result from dynamic interactions within the
      neuronal circuitry, how exactly populations of neurons become synchronized
      remains largely to be clarified. We propose that astrocytes are directly involved
      in the generation of neuronal synchrony in the hippocampus. By using a
      combination of experimental approaches in hippocampal slice preparations,
      including patch-clamp recordings and confocal microscopy calcium imaging, we
      studied the effect on CA1 pyramidal neurons of glutamate released from astrocytes
      upon various stimuli that trigger Ca2+ elevations in these glial cells, including
      Schaffer collateral stimulation. We found that astrocytic glutamate evokes
      synchronous, slow inward currents (SICs) and Ca2+ elevations in CA1 pyramidal
      neurons by acting preferentially, if not exclusively, on extrasynaptic NMDA
      receptors. Due to desensitization, AMPA receptors were not activated by
      astrocytic glutamate unless cyclothiazide was present. In the virtual absence of
      extracellular Mg2+, glutamate released from astrocytes was found to evoke, in
      paired recordings, highly synchronous SICs from two CA1 pyramidal neurons and, in
      Ca2+ imaging experiments, Ca2+ elevations that occurred synchronously in domains
      composed of 2-12 CA1 neurons. In the presence of extracellular Mg2+ (1 mM),
      synchronous SICs in two neurons as well as synchronous Ca2+ elevations in
      neuronal domains were still observed, although with a reduced frequency. Our
      results reveal a functional link between astrocytic glutamate and extrasynaptic
      NMDA receptors that contributes to the overall dynamics of neuronal synchrony.
      Our observations also raise a series of questions on possible roles of this
      astrocyte-to-neuron signaling in pathological changes in the hippocampus such as
      excitotoxic neuronal damage or the generation of epileptiform activity.

PMID- 16646156
TI  - Neuronal dysfunction in Down syndrome: contribution of neuronal models in cell
      culture.
AB  - Down syndrome (DS) in humans, or trisomy of autosome 21, represents the
      hyperdiploidy that most frequently survives gestation, reaching an incidence of 1
      in 700 live births. The condition is associated with multisystemic anomalies,
      including those affecting the central nervous system (CNS), determining a
      characteristic mental retardation. At a neuronal level, our group and others have
      shown that the condition determines marked alterations of action potential and
      ionic current kinetics, which may underlie abnormal processing of information by
      the CNS. Since the use of human tissue presents both practical and ethical
      problems, animal models of the human condition have been sought. Murine trisomy
      16 (Ts16) is a model of the human condition, due to the great homology between
      human autosome 21 and murine 16. Both conditions share the same alterations of
      electrical membrane properties. However, the murine Ts16 condition is unviable
      (animals die in utero), thus limiting the quantity of tissue procurable. To
      overcome this obstacle, we have established immortal cell lines from normal and
      Ts16 mice with a method developed by our group that allows the stable in vitro
      immortalization of mammalian tissue, yielding cell lines which retain the
      characteristics of the originating cells. Cell lines derived from cerebral
      cortex, hippocampus, spinal cord and dorsal root ganglion of Ts16 animals show
      alterations of intracellular Ca2+ signals in response to several
      neurotransmitters (glutamate, acetylcholine, and GABA). Gene overdose most likely
      underlies these alterations in cell function, and the identification of the
      relative contribution of DS associated genes on such specific neuronal
      dysfunction should be investigated. This could enlighten our understanding on the
      contribution of these genes in DS, and identify new therapeutic targets.

PMID- 16646157
TI  - Polyamine and aminoguanidine treatments to promote structural and functional
      recovery in the adult mammalian brain after injury: a brief literature review and
      preliminary data about their combined administration.
AB  - The regeneration potential of the adult mammalian central nervous system (CNS) is
      very modest, due to, among other factors, the presence of either a glial scar, or
      myelin-associated regeneration inhibitors such as Nogo-A, MAG and OMgp, which all
      interact with the same receptor (NgR). After a brief review of the key proteins
      (Rho and PKC) implicated in NgR-mediated signalling cascades, we will tackle the
      implications of cAMP and Arginase I in overcoming myelin growth-inhibitory
      influence, and then will focus on the effects of polyamines and aminoguanidine to
      propose (and to briefly support this proposal by our own preliminary data) that
      their association might be a potent way to enable functionally-relevant
      regeneration in the adult mammalian CNS.

PMID- 16646158
TI  - Rotating sample system: an equivalent of a rotating electrode for microliter
      samples.
AB  - Voltammetric experiments in sample droplets of 20 microL volume were carried out
      with gold ring electrodes microfabricated on Pyrex substrates. The droplet
      studied was centered and kept in place by a hydrophobic ring deposited on the
      substrate around the ring electrode, which also ensured that each sample assume a
      semispherical shape. A small hole in the center of the substrate filled with an
      agar gel membrane served as a junction. A mild jet of humidified nitrogen gas
      directed tangentially at the droplet caused it to rotate at a high rate. Cyclic
      voltammetry and constant-potential electrolysis of potassium ferricyanide were
      used to characterize this rotating sample system and to calculate diffusion layer
      thickness. The results clearly demonstrate that rotating of a semispherical
      microsample placed above a stationary ring electrode with a mild gas jet can be
      as effective as a rotating electrode system. As a practical example, voltammetric
      stripping analysis of 20-120 pmol mercuric nitrate samples was performed with a
      calibration of good linearity (r2 = 0.988) and a time constant for exhaustive
      electrolysis of approximately 2 min.

PMID- 16646159
TI  - High rate of immediate systemic hypersensitivity reactions to tiger snake
      antivenom. Comment.

PMID- 16646160
TI  - [Nuclear receptor and inflammation].

PMID- 16646161
TI  - [Rheumatic collagen diseases and drug-induced kidney disorders].

PMID- 16646162
TI  - [Registry of cases with primary immunodeficiency syndrome in Japan].

PMID- 16646163
TI  - [Methotrexate therapy for rheumatism and collagen diseases].

PMID- 16646164
TI  - [Clinical studies on glucocorticoid-induced osteoporosis].

PMID- 16646166
TI  - Facility profile. Designers dig down for space solution.

PMID- 16646165
TI  - Take control of energy costs--now!

PMID- 16646167
TI  - Shop smart. Electrical deregulation is here.

PMID- 16646168
TI  - Rx for SBS. Suspect sick building syndrome? Get a diagnosis from the experts.

PMID- 16646169
TI  - Easy riders. Discrete elevator groupings are the key to hassle-free, hygienic
      rides for all.

PMID- 16646170
TI  - Window shopping.

PMID- 16646171
TI  - Quake take. A look at California's earthquake retrofit regs.

PMID- 16646172
TI  - Waste watchers. Heads up! Feds now monitor local med waste hauling.

PMID- 16646173
TI  - Assessing a student's perception of a curriculum.

PMID- 16646174
TI  - Promoting organ donation awareness on a university campus.

PMID- 16646175
TI  - Emotional intelligence: enhancing student effectiveness and patient outcomes.

PMID- 16646176
TI  - Eyes in the back of my head: unobtrusive student evaluation.

PMID- 16646177
TI  - Cross-cultural comparison of the concerns of beginning baccalaureate nursing
      students.

PMID- 16646178
TI  - Academic dishonesty and professional practice: a convocation.

PMID- 16646179
TI  - Painless injections: Heifer Skin Tap Technique.

PMID- 16646180
TI  - Assign it and they will read! Or will they? Reading activities of nursing
      students.

PMID- 16646181
TI  - Educational technology and the faculty role: what you don't know can hurt you.
AB  - The proliferation of teaching strategies using the Internet and other educational
      technology innovations has created new employment issues in higher education. The
      authors discuss forces influencing the increasing use of on-line instruction,
      factors to consider before venturing into the virtual academy, and the faculty
      role in shaping policy related to distributed education in their institutions and
      academia in general.

PMID- 16646182
TI  - The NURSE Center: A peer mentor-tutor project for disadvantaged nursing students
      in Appalachia.
AB  - To assist disadvantaged Appalachian nursing students, a grant-supported peer
      mentor-tutor project was initiated in a regional university. Located in the NURSE
      Center (Nursing Undergraduate Resource for Successful Education), the goals of
      the project were to improve participants'academic achievement, increase
      retention, encourage timely academic progression, and improve NCLEX-RN passing
      rates. The authors describe the project, the first year of operation, and future
      directions.

PMID- 16646183
TI  - Teaching the process of developing a professional portfolio.
AB  - The changing healthcare environment is placing new demands on today's
      professionals to demonstrate evidence of their continued competence to practice.
      Obtaining relicensure may soon require the use of a professional portfolio. In
      many instances, portfolios are already necessary for recertification by some
      specialty organizations. The author describes a course that teaches students how
      to prepare a professional portfolio.

PMID- 16646184
TI  - Community Partnerships: A win-win situation.

PMID- 16646185
TI  - Teaching students safer methods of patient transfer.
AB  - Lifting patients is a major contributor to back injuries. The commonly used
      method for lifting patients, the under-axilla grasp method, exceeds the level of
      force that can safely be exerted to the lumbar-sacral area of the spine. Using
      assistive devices decreases the injury rate. The author discusses how student
      nurses can be taught to use assistive devices and thus avoid the under-axilla
      grasp method of transfer

PMID- 16646186
TI  - The cookie experiment revisited: broadened dimensions for teaching nursing
      research.
AB  - Nurse educators face the ongoing challenge of presenting increasingly complex
      nursing research methods to undergraduate and graduate students. The cookie
      experiment, a unique teaching strategy developed more than a decade ago by Thiel,
      has been refined and expanded to include hands-on quantitative and qualitative
      components while also serving as a way to lessen students'phobias about research.
      This creative and effective teaching strategy provides a user-friendly format
      that can be adapted as needed to present both basic and complex research
      concepts. The authors present this teaching strategy and discuss its
      applicability to undergraduate and graduate courses.

PMID- 16646187
TI  - The NCLex Examination: preparing for future nursing practice.
AB  - One nursing organization that closely tracks the direction of healthcare and
      nursing practice is the National Council of State Boards of Nursing, Inc. As the
      developer of the National Council Licensure Examination for Registered Nurses
      (NCLEX-RN examination), maintaining currency of the examination is of primary
      importance to the National Council. The authors discuss recent trends in the
      NCLEX-RN Test Plan.

PMID- 16646188
TI  - Evaluation of Internet sources.

PMID- 16646189
TI  - How Toby discovered healthy food.

PMID- 16646190
TI  - Nursing students and computerized charting: lessons learned.

PMID- 16646191
TI  - Facilitating health education and promotion in the childbearing community client.

PMID- 16646192
TI  - Artist-in-Residence Program.

PMID- 16646193
TI  - Using computer technology to teach critical thinking.

PMID- 16646194
TI  - Home health care across the ADN curriculum.

PMID- 16646195
TI  - Drug calculations examinations: do calculators make a difference?

PMID- 16646196
TI  - Clinical probation: supporting the at-risk student.

PMID- 16646197
TI  - Encouraging collaborative learning among culturally diverse students.
AB  - With the dramatic increase in the number of foreign-born residents in many U.S.
      communities, it is increasingly important that nursing education address the
      requirements of culturally competent care, The author describes the experience of
      establishing a teaching and learning environment to foster this concept. The
      setting was a health assessment course with students from 13 countries of origin.
      Emphasis is placed on effective teaching strategies, student contributions to the
      process, and the challenges that remain.

PMID- 16646198
TI  - Academic-based nurse-managed centers: six key questions.
AB  - A school of nursing that is planning an academic-based nurse-managed center must
      consider the many implications of this action. It requires a long-term commitment
      to the community and to the individual clients served, and time, energy, and
      consistent funding will be needed to maintain viability. Six key questions that
      must be answered are explored.

PMID- 16646199
TI  - New horizons: fostering BSN students' interest in nursing research.

PMID- 16646200
TI  - Nursing journal survey: information to help you publish.
AB  - To help others succeed in getting their work published, the authors share
      findings from a survey of 83 journal editors. The main reasons cited by editors
      for rejecting manuscripts are discussed. Facts about journal foci, acceptance
      rates, time from submission to acceptance, time lag between final copy submission
      and publication, preferred editorial styles, web site addresses, and e-mail
      submissions are included in the tables. The primary steps from writing to
      publication are also reviewed.

PMID- 16646201
TI  - Everything you learned about health you learned in grade school.

PMID- 16646202
TI  - Transitions: A new model for nursing curricula.
AB  - Nurses in the next millennium will be asked to adopt new, broader roles across a
      wider variety of practice settings. The Healing Community is a consortium of
      nurse educators at six schools of nursing who formed a partnership to address
      these needs and explore solutions. The result is a shared curriculum, based on
      the concept of transitions. The authors describe the transitions model and the
      transitional process experienced by members of the Healing Community.

PMID- 16646203
TI  - The clinical achievement portfolio: an outcomes-based assessment project in
      nursing education.
AB  - Dynamic healthcare market forces impel educators to search for innovative methods
      of academic assessment to measure learning outcomes. The clinical achievement
      portfolio is a creative and systematic tool for documenting continuous
      improvement of student clinical learning. The authors describe the use of the
      portfolio as a pilot project aimed at introducing reflective thinking and
      measuring clinical learning in undergraduate nursing education. Potential
      benefits of the clinical portfolio and implications for future research are
      proposed.

PMID- 16646204
TI  - Complementary therapies: introduction into a nursing curriculum.
AB  - With the increasing use of complementary therapies by the general population,
      nursing faculty are challenged to educate their students about these therapies.
      The authors designed a course to provide students with a broad overview of
      selected complementary therapies commonly used in the United States. In
      preparation for the course, the authors evaluated graduate nursing students'
      awareness, use, and practice patterns of complementary therapies in their rural
      state. A high percentage (82%) of those students thought it was important for
      healthcare professionals to understand complementary therapies. The course has
      been offered three times, once using an interactive video network and twice using
      a 5-day workshop format.

PMID- 16646206
TI  - What's on the minds of CIOs?

PMID- 16646205
TI  - Stress management strategies for women doctoral students.
AB  - When women return to school part-time for the doctorate while continuing to work
      full-time, they face many changes in their lives. Adding the role of doctoral
      student to existing roles at work and home can be challenging for women. By using
      stress-reducing strategies aimed at managing role changes, time pressures, and
      education issues, women can successfully integrate the student role into their
      daily lives.

PMID- 16646207
TI  - Tablet PCs in the spotlight.

PMID- 16646208
TI  - New strategy: image is everything.

PMID- 16646209
TI  - Health records in your pocket.

PMID- 16646210
TI  - Building I.T. on hope and a shoestring.

PMID- 16646211
TI  - Readers' perspectives...RHIOs eventually will become advisory/governing bodies?

PMID- 16646212
TI  - Alveolar bias in the final consonant deletion patterns of African American
      children.
AB  - PURPOSE: The variable deletion of word-final consonants is a well-known feature
      of African American English (AAE). This study aimed to show whether African
      American children exhibit an alveolar bias in their deletion of final voiceless
      stops as has been observed for their production of final nasals. METHOD: The data
      were extracted from more than 5000 spontaneous utterances in the speech samples
      of 7 African American children at 32 to 36 months of age. RESULTS: The final
      alveolar voiceless stop /-t/ was deleted significantly more often in word-final
      position than were /-p/ and /-k/ in both singleton and clustered contexts. The
      deletion of /-t/ in final clusters preceding other consonants at word boundaries
      contributed significantly to this bias. No significant differences were observed
      among the stops in their relative frequencies of deletion when a vowel sound
      followed or when the final stop was prepausal at word boundaries. CONCLUSION:
      African American children's deletion of final consonants is patterned even at an
      early age. It varies with whether the voiceless stop consonant is an alveolar
      sound or not and with the type of phonetic context in which the alveolar stop is
      embedded. This alveolar stop bias was attributed to phonetic and grammatic
      constraints on articulating final /-t/ relative to final /-p/ and /-k/. CLINICAL
      IMPLICATION: All final consonant deletion patterns should not be regarded as
      typical of African American children when assessing their speech even as early as
      age 3;0 (years;months).

PMID- 16646213
TI  - Effects of prolonged loud reading on normal adolescent male voices.
AB  - PURPOSE: The purpose of this article was to test the effects of vocal loading in
      healthy, peripubescent teenage boys. It was hypothesized that select acoustic
      measures, ratings of physical appearance of the larynx, and self-ratings of
      physical effort and vocal quality in the experimental group would significantly
      change in response to 2 hr of prolonged loud reading. METHOD: In this
      prospective, repeated measures study, 25 boys aged 13-16 years were randomly
      assigned to either an experimental group (2 hr of continuous loud reading) or a
      control group (silent reading with brief periods of conversation). Pre-post
      acoustic, videoendoscopic, and perceptual data including self-ratings were
      collected. Postreading recovery changes were tracked by monitoring average
      reading fundamental frequency (F0) and intensity for 20 min following cessation
      of the reading task. RESULTS: The experimental group demonstrated statistically
      significant differences before and after prolonged loud reading for three
      variables: F0 (p < .01), self-ratings of vocal quality (p < .01), and physical
      effort (p < .01). No pre-post changes were evident in the control group. In the
      experimental group, posttest return of F0 to pretest levels occurred within 20
      min. Self-ratings revealed that the boys felt that their voice quality worsened
      and physical effort increased during the experimental task. Expert ratings did
      not detect any significant differences in either the perceptual quality of the
      experimental group's voices or their videoendoscopic images. IMPLICATIONS: These
      findings demonstrate that prolonged loud reading can induce temporary but
      measurable changes in F0 and in self-perception of vocal function in adolescent
      males who are experiencing a period of rapid laryngeal growth. The underlying
      mechanism for these changes remains unclear and warrants continued investigation.
      Furthermore, the results suggest that in the pubescent male population,
      comparable vocal loading tasks encountered in daily use should not result in long
      term negative effects.

PMID- 16646214
TI  - Survey of SLP caseloads in Washington State schools: implications and strategies
      for action.
AB  - PURPOSE: To document statewide and regional caseloads and to examine workload
      management strategies by surveying speech-language pathologists (SLPs) in
      Washington State public schools. METHOD: All school SLPs who were registered with
      the Office of the Superintendent of Public Instruction were mailed a detailed
      survey in May, 2001 and a brief follow-up survey 1 year later. RESULTS: Response
      rates were 43% (N=431) and 47% (N=464), respectively. Caseload findings showed a
      statewide mean of 59 students, with regional variation as high as 30%.
      IMPLICATIONS: There was no systematic evidence that caseloads were managed
      through state, district, or local limits or by distributing clients on the basis
      of the severity of impairment or SLP experience ortraining. There was significant
      evidence, however, that clinicians with larger caseloads were more likely to have
      assistants and to conduct a higher proportion of group sessions than were
      clinicians with smaller caseloads. The authors discuss the implication of these
      findings for and other states with no caseload limits and a shortage of SLPs.
      There is an appeal for more research using newly established measures of workload
      as well as a call to action to address the challenges that these findings
      represent.

PMID- 16646215
TI  - Treating preschool children who stutter: description and preliminary evaluation
      of a family-focused treatment approach.
AB  - PURPOSE: The purpose of this article is to present a detailed description of a
      family-focused treatment for preschool children who stutter that addresses
      communication behaviors and attitudinal reactions that children and their parents
      may exhibit in reaction to stuttering, as well as a preliminary evaluation of the
      outcomes of that treatment. METHOD: The study involved assessment of the
      children's speech fluency and a client satisfaction questionnaire that sought
      parents' opinions about which aspects of the treatment were beneficial.
      Participants were 17 children who stutter, ages 31 to 62 months, and their
      families. RESULTS: Responses to the questionnaire indicated that treatment helped
      families learn about stuttering and about strategies that facilitate children's
      fluency. Evaluation of the children's fluency revealed that all participants
      achieved improved fluency at the conclusion of treatment and at long-term follow
      up. IMPLICATIONS: Findings suggest that this treatment approach may be useful for
      helping children achieve improved speech fluency, effective communication skills,
      and healthy communication attitudes.

PMID- 16646216
TI  - Comparing monotic and diotic selective auditory attention abilities in children.
AB  - PURPOSE: Some researchers have assessed ear-specific performance of auditory
      processing ability using speech recognition tasks with normative data based on
      diotic administration. The present study investigated whether monotic and diotic
      administrations yield similar results using the Selective Auditory Attention
      Test. METHOD: Seventy-two typically achieving children were tested both
      monotically and diotically in a counterbalanced, repeated measures design.
      RESULTS: Results revealed that diotic scores were significantly higher than
      monotic scores, with no significant difference between right and left ears.
      CONCLUSION: Collecting ear-specific normative data is recommended over
      extrapolating from norms using a diotic speech recognition test. Because a
      binaural advantage may be found when listening under challenging conditions, the
      strategy of occluding one ear in children with (central) auditory processing
      disorder ([C]APD) should be reconsidered.

PMID- 16646217
TI  - Performance of African American preschool and kindergarten students on the
      expressive vocabulary test.
AB  - PURPOSE: To examine the validity of the Expressive Vocabulary Test (EVT; K.
      Williams, 1997) for assessing the expressive vocabulary skills of African
      American students. METHOD/RESULTS: One hundred sixty-five African American
      preschool and kindergarten students were administered the EVT. The mean EVT score
      for these African American students was 96.44 (SD = 11.42), which is not
      appreciably lower than the standardized mean of 100 (SD=15). CLINICAL
      IMPLICATIONS: Scores were normally distributed, indicating that the EVT is
      culturally fair and appropriate for use with some African American preschool and
      kindergarten children as part of an early screening battery. The importance of
      culturally fair vocabulary measures is discussed relative to this population.

PMID- 16646218
TI  - [Pituitary surgery demands cooperation. Good results with a team of
      endocrinologists, ophthalmologists, radiologists and neurosurgeons].

PMID- 16646219
TI  - [Assessment of pituitary surgery. Good tumor reduction according to the SIPAP
      classification].

PMID- 16646220
TI  - [There is a need to reform dementia care. Resources are not used optimally--time
      for evidence-based care].

PMID- 16646221
TI  - [Deep venous thrombosis].

PMID- 16646222
TI  - [Spontaneous rupture of utero-ovarian veins during pregnancy. Severe, acute
      complication lacking an established therapeutic management plan].

PMID- 16646223
TI  - [International Balint conference in Stockholm].

PMID- 16646224
TI  - [Enbrel and heart failure].

PMID- 16646225
TI  - [Management programs needed for students infected with MRSA].

PMID- 16646226
TI  - [Fass 2006--an overweight 40-year-old].

PMID- 16646227
TI  - ["Arms up and stretch" better than the "Grasset test"].

PMID- 16646228
TI  - [Drug eluting stents are drugs and should be scrutinized as such].

PMID- 16646229
TI  - [The discovery of Helicobacter pylori--a revolution in gastroenterology].

PMID- 16646230
TI  - [Vitamins B in primary health care--requirement, deficiency, adverse effects].

PMID- 16646231
TI  - [Chinese academy of otorhinolaryngology head and neck surgery: a century of
      progress].

PMID- 16646232
TI  - [Current situation and future of research for facial nerve].

PMID- 16646233
TI  - [Landmark of facial nerve in middle ear surgery].
AB  - OBJECTIVE: To re-evaluate landmarks for facial nerve in middle ear surgery
      through temporal bone dissection and facial nerve surgery. METHODS: Some relative
      landmarks were found through 44 facial nerves dissection in cadaver and 106 cases
      of facial nerve decompression surgery. RESULTS: (1) Landmarks for vertical
      segment of the facial nerve: the vertical line in combined point between
      posterior and middle 1/3 horizontal semicircular canal clews the posterior edge
      of facial nerve; the prolong line of superior radian of incus short process clues
      to the anterior edge of the facial nerve, the facial nerve and horizontal
      semicircular canal are almost in the same plane. (2) Landmarks for horizontal
      segment of the facial nerve: the facial nerve tracks forward inferior to short
      process of incus and anterior to horizontal semicircular canal carina in 30
      angel. The facial nerve, locating posterior and superior to cochleariform process
      and parallel with it, forms the step of middle-superior tympanic cavity and
      tracks forward to geniculate ganglion. (3) location of geniculate ganglion: The
      same distance prolong line of stapes head to cochleariform process clues to
      geniculate ganglion. (4) Location of the chorda tympani nerve: chorda tympani
      nerve, leaving tympanic sulcus at 3 clock of bone canaline left ear and at 9
      clock of bone canaline right ear, tracks forward along tympani sulcus and then
      cross between long process of incus and manubrium. It lies in the border of pars
      tensa and pars flaccid and is about 5 - 8 mm from the stylomastoid foramen to
      where the chorda tympani nerve leaves the facial nerve. There is no difference of
      facial nerve structure in temporal bone dissection and in surgery. CONCLUSIONS:
      The fixed landmarks of middle ear are the frame of reference of facial nerve, in
      which horizontal semicircular canal is most invariable; and the safety of surgery
      will be improved by the reference of the facial nerve.

PMID- 16646234
TI  - [Clinical research about the distribution of perineural vascular plexus of the
      facial nerve].
AB  - OBJECTIVE: To objectively evaluate the usefulness and the reliability of the
      perineural vascular plexus as a landmark for facial nerve as well as whether it
      will be a landmark for identification of the facial nerve in surgery for otology
      and neurotology by means of investigating the location of the facial nerve for
      prevention of iatrogenic facial palsy. METHODS: Prospective case series were
      designed. Three hundred and eleven consecutive patients were studied which
      required tympanoplasty for chronic otitis media or microsurgery for facial nerve
      decompression and congenitally malformation of the ear from July 2002 to July
      2005. All the patients were operated by the first author. Perineural vascular
      plexus as a landmark for identification of the facial nerve in surgery were
      observed to assess the utility. RESULTS: The well recognized perineural vascular
      plexus were seen on the horizontal mesotympanic segment of the nerve in 95.8% of
      patients (298 cases), and only in 4.2% of the patients (13 cases), the vessel
      plexus was difficult to identify. The 95% confidence interval was from 93.6% to
      98.0%. CONCLUSIONS: The vascular plexuses around or over the horizontal portion
      of the facial nerve provide an early and direct indicator of the location of the
      facial nerve. The perineural vascular plexus could be a dependable and reliable
      landmark for the identification the horizontal part of the facial nerve in
      surgery for otology and neurotology.

PMID- 16646235
TI  - [Experimental study of the facial nerve paralysis induced by herpes simplex virus
      type 1 infection in mice].
AB  - OBJECTIVE: To establish an animal model of Bell palsy induced by type I herpes
      simplex virus (HSV-1) infection and to assess the role and site of HSV-1 in the
      pathogenesis of facial paralysis. METHODS: Fifty-three female Balb/c mice four
      week-old weighted 16-18 g were studied. After scratching the surface of bilateral
      auricles with a 26-gauge needle, 25 microL HSV-1 with a titer of 6. 7 x 10(7)
      PFU/ml was inoculated into the right auricle, and the same volume of PBS was
      placed in the left. As a control, PBS was placed on the bilateral auricles of 4
      mice. The HSV-1 DNA in bilateral facial nerve, bilateral brainstem, bilateral
      trigeminal carrier ganglion, bilateral brain, and blood at different stage was
      examined with polymerase chain reaction analysis. RESULTS: Thirty-seven animals
      (75.51%) appeared different degree facial paralysis among the 49 inoculated
      animals. Fourteen facial paralysis (37.84%) were on the right, 3 (8.11%) on the
      left, and 20 (54.05%) on the bilateral side. Six animals with facial palsy were
      recovered during 3-13 days, the average recovery time was 7.83 days. CONCLUSIONS:
      The existence of HSV-1 in the brainstem and the cerebral cortex is significant
      for facial paralysis.

PMID- 16646236
TI  - [Animal model of facial neuritis induced by herpes simplex virus].
AB  - OBJECTIVE: To study the role of herpes simplex virus type 1 ( HSV-1 ) in facial
      paralysis by developing an experimental animal model of viral facial paralysis.
      METHODS: Both sides of posterior auricular branch of facial nerve were anatomies
      and incised in 66 mice. The HSV-1 was inoculated into right ear branch and fetal
      bovine serum was inoculated into left ear branch as control. The symmetry of
      mouse face was observed and scored. The temporal bones were serially sectioned
      and stained with hematoxylin and eosin. The extratemporal facial nerves were
      stained with osmium tetroxide. HSV-1 DNA in bilateral facial nerve, brain stem,
      trigeminal ganglion and spinal cord was detected by the polymerase chain
      reaction. RESULTS: Twenty-eight (42. 42%) mice developed right facial paralysis
      between 2 and 5 days after inoculation. Continuing 3-6 days, the facial paralysis
      recovered spontaneously. Thirty-eight mice had no signs of facial paralysis.
      Compared with the left, nerve swelling, inflammatory cell infiltration were
      manifested in right temporal facial nerve of paralyzed mice. The ratio of the
      cross-sectional area of the facial nerve to the facial canal ( FN/FC ) was
      significantly higher than that on the control side (P < 0.01). Demyelinated nerve
      fibers were seen in the right extratemporal facial nerve. Not only in paralyzed
      mice, but also in non-paralyzed mice, HSV DNA was detected in some nerve tissues.
      CONCLUSIONS: Inoculating HSV-1 into posterior auricular branch of facial nerve
      can produce an acute and transient facial paralysis in mice. The possible
      pathophysiologic mechanism of the facial paralysis is viral invasion and
      transportation from distal branch to main trunk. Then the viral facial neuritis
      causes facial paralysis.

PMID- 16646237
TI  - [Facial nerve grading system].

PMID- 16646238
TI  - [Summary of national otologic conference].

PMID- 16646239
TI  - [Management of operative complications in acoustic neuroma surgery].
AB  - OBJECTIVE: To explore the common complications related to acoustic neuromas and
      to search methods for preventing from them. METHODS: One hundred and five
      patients with acoustic neuromas underwent 110 operations with the retrosigmoid
      approach, middle cranial fossa approach and labyrinth approach. All cases were
      followed up more than 1 month after surgery. RESULTS: Of 110 cases, the most
      frequent complication was hearing disability which occurred in 95 cases (95/110,
      86.4%). and the facial paralysis was in 63.6% (70/110) after one month. Other
      complications were cerebrospinal fluid fistulas (CSF, 12.7%, 14/110) ,
      intracranial hematoma (5.5%, 6/110), cranial nerve palsies (4.5%, 5/110),
      meningitis (3.6%, 4/110), tetraparesis (3.6%, 4/110), balance disturbance (1.8%,
      2/110), hemiparalysis and anepia (0.9%, 1/110). Effective stopping bleeding
      during operation and controlling blood pressure after operation, as well as
      keeping effective sedation in 24 hours after operation were the important ways to
      prevent from intracranial hematoma The haemorrhage often accrued in 48 hours post
      operation. CSF in this series was another common complication in acoustic neuroma
      surgery. Ten cases with CSF subcutaneous retro-auricular had been successfully
      controlled by conservative treatment. Of 4 cases with rhinorrhea CSF, 3 of them
      were required surgical management, another one got self-cure by bed rest. The
      ventricular drainage pro-operation was the most important procedure for drawdown
      the hypsi-cranium pressure. CONCLUSIONS: The key factors to avoid the
      complications include mastering the anatomy of different surgical approach, how
      much of the tumor size, surgical experience and preoperative evaluation of
      patients' imaging information and other clinical data.

PMID- 16646240
TI  - [Morphological study of thick basement membrane-like layer in chronic
      rhinosinusitis].
AB  - OBJECTIVE: To observe the thick basement membrane-like layer under the damaged
      epithelium in patients with chronic rhinosinusitis (CRS) and to study its
      principal components. METHODS: Patients (n = 40) with CRS undergoing functional
      endoscopic sinus surgery were recruited for the study. Patients (n = 10) with no
      evidence of sinus disease were used as control subjects. Ethmoidal sinus mucosa
      specimen were stained by PAS staining to measure the thickness of basement
      membrane-like layer. Immunohistochemical staining, picrosirius-polarization
      method and transmission electron microscopy (TEM) were used to analyse the nature
      of the layer. RESULTS: The thickness of basement membrane-like layer in CRS type
      I and CRS type II were significantly increased compared with normal control
      subjects (t = 5. 426, P < 0. 01; t = 8. 375, P < 0.01). The thickness of CRS type
      II was significantly greater compared with CRS type I (t = 3. 908, P < 0.01).
      There was no difference between atopic group and inotropic group (t = 0.803, P>
      0.05). There was no expression of fibronectin, laminin, IgA, IgG and IgM in the
      thick basement membrane-like layer. A thick reticular structure containing
      collagen fibrils and devoid of cellular elements was observed by TEM.
      CONCLUSIONS: This study demonstrates that a long-standing chronic inflammation
      leads to deposition of collagens type I , III and IV under the damaged
      epithelium, resulting in an increasingly thick sub-basement membrane layer.

PMID- 16646241
TI  - [Anatomic study of pterygopalatine fossa under endoscope].
AB  - OBJECTIVE: To provide endoscopic anatomic bony structures of pterygopalatine
      fossa for skull base surgery. METHODS: The bony structures of the pterygopalatine
      fossa were observed in ten dry skulls under endoscope. RESULTS: The
      pterygopalatine fossa showed a long and narrow cleft composed of the body and
      pterygoid process of sphenoid bone, the lamina perpendicular of palatine bone,
      and the posterior wall of maxillary sinus. The pterygopalatine fossa is (21.4 +/-
      0.8) mm x (5.2 +/- 0.3) mm x (3.2 +/- 0.3) mm, with seven paths communicating
      with nasal cavity, mouth cavity, pharynx, orbit, infratemporal fossa and middle
      cranial fossa. Under endoscope,the whole pterygopalatine fossa could be observed.
      CONCLUSIONS: Endoscopic anatomic study of the pterygopalatine fossa is important
      to endoscopic endonasal skull base surgery. Under endoscope,the whole
      pterygopalatine fossa can be observed.

PMID- 16646242
TI  - [Value of elective neck dissection in patients with clinically stage I squamous
      cell carcinoma of the tongue].
AB  - OBJECTIVE: To determine the value of elective neck dissection in patients with
      clinically stage I (cT1N0M0) squamous cell carcinoma of the tongue. METHODS: This
      was a retrospective study of patients with surgical treatment between November
      1984 and November 1999. A total of 130 patients were included in the study, all
      of whom received operation of the primary site, meanwhile, 99 of whom underwent
      elective neck dissection simultaneously including level I -III or level I -IV
      neck dissection in 20 patients and level I - V neck dissection in 79 patients.
      Results Among all these patients, the rate of occult metastasis to the neck were
      12. 0%. Local failure rate in patients with only local treatment, level I II, II,
      III/IV neck dissection and level I - V neck dissection were 25. 8%, 15. 0% and 7.
      6% respectively. There were significant difference in regional failure between
      patients with only local treatment and patients with elective neck dissection (P
      < 0.05). Also, no significant differences were noted in the survival rate between
      patients with only local treatment, elective neck dissection (level I -III or
      level I -IV) and level I -V neck dissection (P > 0.05). CONCLUSIONS: Elective
      neck dissection significantly reduced regional control failure but was not able
      to reduce distant metastasis or increase the overall survival. A prospective
      randomized study is worthwhile to further evaluate the benefit of elective neck
      dissection in the treatment of clinically stage I squamous cell carcinoma of the
      tongue.

PMID- 16646243
TI  - [One case of parotid gland fistula caused by the external auditory canal
      cholesteatoma].

PMID- 16646244
TI  - [Kanamycin induced ototoxicity in three kinds of mouse strains and its effects on
      the expression of na-K-2Cl co-transporter-1 in stria vascularis].
AB  - OBJECTIVE: To establish a mice model of aminoglycoside antibiotics (AmAn) induced
      ototoxicity. Then to investigate the sensitivity of AmAn induced ototoxicity in
      three mouse strains and effect of kanamycin on the expression of Na-K-2Cl co
      transporter-1 (NKCC1) in stria vascularis. METHODS: C57BL/ 6J, CBA/CaJ, NKCC1 +/-
      mice (each of twenty-four) were randomly divided into four experimental groups A,
      B, C and D (A kanamycin alone, B kanamycin plus 2, 3-dihydroxybenzoate, C 2, 3
      dihydroxybenzoate alone, D control group). Mice were injected with kanamycin
      or/and 2, 3-dihydroxybenzoate for 14 days. Auditory function was measured by
      auditory brainstem response (ABR) and morphology of cochlea was observed by
      succinate dehydrogenase staining. Expression of NKCC1 was detected by
      immunohistochemistry. RESULTS: Mice in group A developed significant ABR
      threshold shifts (P < 0.01), which were accompanied by out hair cells loss. Mice
      in group B significantly attenuated ABR threshold shifts with out hair cells loss
      (P <0.01). The immunostaining of NKCC1 in stria vascularis was attenuated
      significantly in group A compared with group D (P < 0.01) while the
      immunostaining in group B was enhanced than which in group A (P < 0.01). CBA/CaJ
      mice has the highest sensitivity to AmAn in three mouse strains. CONCLUSIONS: An
      mouse model of AmAn induced ototoxicity could be established by administration of
      kanamycin. Kanamycin could inhibit the expression of NKCC1 in stria vascularis.
      2, 3-dihydroxybenzoate could attenuate AmAn induced ototoxicity maybe by
      enhancing the expression of NKCC1. Mice that had the characteristic of
      presbycusis didn't show additional sensitivity of AmAn induced ototoxicity.

PMID- 16646245
TI  - [Nasal mucosa remodeling in guinea pig model of allergic rhinitis].
AB  - OBJECTIVE: To explore the feature of nasal mucosa remodeling in experimental
      allergic rhinitis. METHODS: Twenty-four male Hartley guinea pigs (4 weeks, 250 
      300 g) were randomly divided into four groups (control group and allergen
      exposure groups 1 - 3), each group had 6 guinea pigs. Allergen exposure animals
      were sensitized by intraperitoneal (ip) injection of ovalbumin (OVA). Sensitized
      guinea pigs were subjected to either brief or prolonged exposure to allergen.
      Both brief exposure group (allergen exposure groups) and prolonged exposure group
      (allergen exposure group 2 and 3) received a daily intranasal challenge with 5%
      OVA in 0.9% saline from Day 22 to Day 28, the prolonged exposure group (allergen
      exposure group 2 and 3) followed by twice weekly exposure to 5% OVA intranasal
      for an additional 8 and 12 weeks respectively. Control animals were given saline
      only. At 24 h after the last intranasal challenge, the guinea pigs were killed
      and the heads of the animals were removed and fixed in 10% neutral buffered
      formalin for 24 hours, then decalcified in 5% trichloroacetic acid for 10 days.
      The tissue blocks were embedded in paraffin. The paraffin sections 3 microm thick
      were stained with hematoxylin and eosin (HE), alcian blue (pH, 2. 6)-periodic
      acid-Schiff (AB-PAS), and Masson's Trichrome (MT). The infiltrating eosinophils
      in nasal mucosa were examined, AB-PAS-positive cells in the surface epithelium in
      nasal septal mucosa were counted. The percentage area of MT stained extracellular
      matrix in septal mucosa and conchae and damage of epithelium were determined by
      an image analyzer. RESULTS: The control group only presented a few eosinophils.
      Significant eosinophil infiltration was observed in the sensitized groups.
      Compared with control group (intact epithelium 87.7% +/- 11.1%), there was no
      significant epithelial damage in 1 week exposure group. Significant epithelial
      damage were observed in 8 and 12 weeks groups (intact epithelium 36.7% +/- 16.9%,
      37.9% +/- 12.9%, respectively). An increase in AB-PAS-positive cells was observed
      in the mucosa of nasal septum in the prolonged allergen exposure groups, but not
      in the brief allergic inflammation group in comparison with the control. The
      brief OVA exposure group did not show increased collagen fibrils within the
      mucosa of nasal septum and conchae. In contrast, after prolonged OVA exposure an
      increase in matrix was observed. Furthermore, in both the nasal septum and
      conchae, significant increasing of ECM deposition was found in a further
      prolonged exposure for 12 weeks compared to 8 weeks. CONCLUSIONS: Epithelial
      damage, goblet cells hyperplasia and extracellular matrix deposition were
      observed as the features of remodeling in this guinea pig model of allergic
      rhinitis.

PMID- 16646246
TI  - [Anti-nasopharyngeal carcinoma effect in vivo and in vitro of cytotoxicity T
      lymphocyte induced by Ad5-latent membrane protein 2A].
AB  - OBJECTIVE: To study the biological characteristics of cytotoxicity T lymphocyte
      (CTL) induced by dendritic cell (DC) transfected with the Epstein-Barr virus
      latent membrane protein 2A (EBV-LMP2A) recombinant adenovirus. To establish
      nasopharyngeal carcinoma (NPC) animal models expressing LMP2A and investigate the
      anti-tumor effect of LMP2A specific CTL in vivo. METHODS: The mononuclear cells
      were isolated from human peripheral blood mononuclear cells (PBMC) and cultured
      with the cytokines [granulocyto-monocyte colony stimulating factor (GM-CSF),
      interleukin-4 (IL-4) and tumor necrosis factor-alpha TNF-alpha]. The expression
      of surface markers on mature DC was detected by fluorescence activated cell
      sorter FACS. Mature DC were transfected with LMP2A recombinant adenovirus. Under
      the help of interleukin-2 (IL-2), LMP2A specific CTL were induced by coculturing
      LMP2A-transfected DC with autologous PBMC. The population of CTL was detected by
      FACS. NPC animal models were constructed by implanting CNE cells expressing LMP2A
      subcutaneously into BALB/c nude mice. After intra-tumoral injection of LMP2A
      specific CTL, the size of tumor was measured. The tumors were removed after 30 d
      and subjected to histological examination. RESULTS: Mature DC displaying typical
      characteristics of morphology and phenotype were obtained from monocytes cultured
      in the medium containing GM-CSF, IL-4 and TNF-alpha. The LMP2A specific CTL
      induced by transfected DC were composed of mainly CD4+ and CD8+ T cells. The NPC
      animal models were constructed three weeks after implanting CNE cells. The study
      in vivo indicated that the tumors treated with LMP2A specific CTL grew slowly
      compared with control. Tumor volume of treated groups was significantly smaller
      than that of controls. The histological sections showed local necrosis and
      infiltration of lymphocyte in tumor tissue. CONCLUSIONS: Typically mature DC
      could be generated in vitro by culturing monocytes with the cytokines. LMP2A
      specific CTL could be induced by LMP2A transfected DC in vitro. NPC mice models
      could be constructed by implanting CNE cells. LMP2A specific CTL could inhibit
      the growth of implanted tumor and produce an anti-tumor effect in vivo.

PMID- 16646247
TI  - [Effect of survivin antisense oligodeoxynucleotide on carcinoma of larynx in vivo
      and in vitro].
AB  - OBJECTIVE: To observe the effect of survivin antisense oligodeoxynucleotide
      (ASODN) on the apoptosis of human carcinoma of larynx cell line Hep2 and the
      inhibitory rate in nude mice model so as to discuss the selective blocking
      activity of antisense technique on gene expression seeking a new way for gene
      therapy of carcinoma of larynx. METHODS: Antisense oligodeoxynucleotides survivin
      were transformed into human carcinoma of larynx cell line Hep2 by liposome
      Lipofectamine 2000. Within 72 h after transfection, 3-(4,5-dimethylthiazol-2-yl) 
      2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cellular
      proliferation. Forty eight hours after transfection, reverse transcription
      polymerase chain reaction (RT-PCR) assay was used to observe the expression of
      survivin gene, Western Blot assay for the protein, and terminal deoxynucleotide
      mediated nick end labeling (TUNEL) and flow cytometer for cellular apoptosis.
      RESULTS: Cellular inhibition rate of 72 h went up to 52. 5% and 71.4% at 1.0
      micromol/L and 2.0 micromol/L value in Lipo-ASODN groups which differed
      statistically remarkably (P = 0.046), higher than that in controls in MTT assay
      (P =0. 003 and 0. 0004). Forty eight hours after transfection survivin gene
      expression in Lipo-ASODN groups were less than that in control group in RT-PCR
      assay. Survivin protein expression decreased in Western blot. In TUNEL assay,
      nuclear positive staining was observed and the apoptosis peak was observed in
      flow cytometer test, which were absent in controls. In nude mice of carcinoma of
      larynx model, the inhibitory rate in Lipo-ASODN groups got up to 48.1% and 61.3%
      higher than that of controls (P < 0.004 and 0. 0006), which differed remarkably
      (P = 0.032) in a dose-dependently way. CONCLUSIONS: The findings showed that the
      expression of survivin gene and protein induced cellular apoptosis in Hep2 cells
      after transfection of Lipo-ASODN and that the carcinoma of larynx in the nude
      mice model were inhibited by Lipo-ASODN which suggested that antisense technique
      can be an effective means in the gene therapy of carcinoma of larynx.

PMID- 16646248
TI  - [Evaluation of the mastoid air cell system in healthy adults by three-dimensional
      volume rendering technique].

PMID- 16646249
TI  - [Monopolar electrosurgery for pediatric tonsillectomy comparison with
      conventional technique].

PMID- 16646250
TI  - [Transnasal endoscopic repair of nasal septal perforation with pedicled muscle
      periosteum flap from anterior wall of the maxillary sinus].

PMID- 16646251
TI  - [Current study of mesenchymal stem cells in nervous system].

PMID- 16646252
TI  - [Application of survival analysis in the follow-up study].

PMID- 16646253
TI  - [How primary prevention should change].

PMID- 16646254
TI  - [Genetic basis of individual susceptibility].
AB  - Polymorphic forms of genes involved in the control of the various phases of the
      cancerogenic process were associated to a greater individual susceptibility to
      cancer as a consequence of exposures to environmental carcinogenic agents. Some
      of these genes are involved in xenobiotic metabolism, in replication and repair
      of the DNA, in the control of cell cycle and cellular proliferation, of
      apoptosis, of the inflammation process, etc. Although the specific risk
      associated to a single polymorphic gene is generally low, the sanitary meaning
      can be considerable if the frequency of certain polymorphisms is high and the
      exposure is consistent. Furthermore, the combination of more unfavourable alleles
      can determine high risk genotypes. These subjects, probably, will fall ill as
      consequence of an exposure. The development of methodologies which allow the
      genotyping of a big number of genes can allow the identifying of highly
      susceptible subjects.

PMID- 16646255
TI  - [Evaluation of total exposure to benzene and formaldehyde in the European
      countries].
AB  - Benzene and formaldehyde are among the principal components in the air of various
      indoor occupational and non-occupational environments. Both compounds are
      toxicologically relevant for humans as recognized carcinogens. In order to
      evaluate the total exposure and to assess the possible health risk caused by
      benzene and formaldehyde for different population groups at European level, the
      JRC Institute for Health and Consumer Protection in Ispra launched the AIRMEX
      (IndoorAir Monitoring and ExposureAssessment Study) project in October 2003. It
      aims at identifying and quantifying the main indoor pollutants particularly in
      kindergartens, schools and public buildings. It also intends to evaluate the
      overall exposure of people working and occupying these areas. Measuring campaigns
      were carried out in pre-selected indoor environments in various European cities
      (Catania, Athens, Arnhem, Nijmegen, Brussels, Thessaloniki). Preliminary results
      clearly indicate that indoor air concentrations for volatile compounds (VOC)
      including benzene are higher than/or similar to those found outdoors, ranging
      from a few micrograms (about 8 microg/m3) to 281 microg/m3. Outdoor
      concentrations vary from 7 to 153 microg/m3. Personal exposure concentrations are
      generally higher than the indoor/outdoor concentrations. In most cases they are
      twice as high as indoor concentrations (or even higher) and significantly higher
      than outdoor concentrations. Air concentrations of aldehydes inside
      buildings/kindergartens were up to 7-8 times higher than outside. This mostly
      concerns formaldehyde, and it seems that strong indoor sources exist which
      clearly determine the indoor air concentrations. Formaldehyde concentrations in
      public buildings and offices vary from 3 to 30 microg/m3, and those in
      kindergartens vary from 6 to 11 microg/m3 (Arnhem/Nijmegen). The highest values
      for formaldehyde, up to 29,9 microg/m3, were found in Catania, Athens and
      Thessaloniki.

PMID- 16646256
TI  - [European Union's strategies on chemicals].

PMID- 16646257
TI  - [Epidemiological study of populations exposed to high levels of 50 Hz magnetic
      fields].
AB  - The purpose of the present paper is to provide guidelines about the
      implementation of epidemiological studies on populations exposed to particularly
      high levels of 50 Hz magnetic fields, indicatively units of microT. The available
      evidence, in fact, points to a consistent increase of the occurrence of
      neoplastic and neurodegenerative disease and adverse reproductive outcomes
      associated to these levels of exposure. An approach based on the detection of
      high risk groups is proposed. In this frame contrastability between study
      subjects and suitable reference populations is the core issue. Some procedures
      aimed at selecting individuals and populations to be studied are discussed, in
      order to support local environmental and health authorities in setting priorities
      for studies and interventions. Finally, the implications of these studies in
      terms of scientific knowledge and environmental reclamation are examined.

PMID- 16646258
TI  - [Cytotoxicity and genotoxicity of drinking water of two networks supplied by
      surface water].
AB  - OBJECTIVE: Evaluation of cytotoxic and genotoxic load of drinking water in
      relationship to the source of supplies, the disinfection process, and the piping
      system. SETTING: Two treatment/distribution networks of drinking water, the first
      (#1) located near the source, the second (#2) located near the mouth of a river
      supplying the plants. DESIGN: Water samples were collected before (F) and after
      (A) the disinfection process and in two points (R1 and R2) of the piping system.
      The samples, concentrated on C18, were tested for DNA damage in human leukocytes
      by the Comet assay and for gene conversion, reversion and mitochondrial
      mutability in Saccharomyces cerevisiae D7 strain. MAIN OUTCOME MEASURES: The
      approach used in this study is able to identify genotoxic compounds at low
      concentration and evaluate their antagonism/synergism in complex mixtures.
      RESULTS: Comet assay results show that the raw water quality depends on the
      sampling point, suggesting that a high input of environmental pollutants occurred
      during river flowing; they also show that the disinfection process can both
      detoxify or enhance biological activity of raw water according to its quality and
      that the piping systems do not affect tap water cytotoxic/genotoxic load. The
      yeast tests indicate the presence of some disinfection by-products effective on
      mitochondrial DNA. CONCLUSION: The biological assays used in this study are
      proven to be able to detect the presence of low concentrations of toxic/genotoxic
      compounds and assess the sources of their origin/production.

PMID- 16646259
TI  - [Assessment of occupational exposure to PAH in coke-oven workers of Taranto steel
      plant through biological monitoring].
AB  - OBJECTIVE: This study aims at evaluating the occupational exposure to polycyclic
      aromatic hydrocarbons (PAH) through biological monitoring and at investigating
      the influence of selected genetic polymorphisms on the levels of internal dose
      biomarker. DESIGN: A cross-sectional study has been conducted on the basis of
      biological measurements in order to evaluate the levels of PAH exposure. SETTING:
      PAH exposure assessment has been carried out in a coke-oven of one of the largest
      European steel plants (ILVA, Taranto), in the context of the program of medical
      surveillance carried in collaboration with the ILVA Occupational Health Service.
      PARTICIPANTS: 355 coke-oven workers exposed to PAH were enrolled from the 3
      batteries of the coke oven plant. Maintenance workers and industrial cleaners
      were included. MAIN OUTCOME MEASURES: The measurement of urinary levels of 1
      hydroxypyrene (1-OHP) as biomarker of internal dose has been carried out, as well
      as the evaluation of metabolic polymorphisms of the cytochrome P450 1A1 (CYP1A1),
      glutathione S-transferases mu (GSTM1) and theta (GSTT1) as biomarkers of
      susceptibility. RESULTS: The median value of urinary 1-OHP was 1,05
      microMol/Molcreat. The difference between the groups was statistically
      significant, with the highest value observed in the maintenance group (median
      1,71, range 0,06-14,69 microMol/Molcreat). It is remarkable that 25% of the
      workers exceeded the proposed benchmark guideline value of2,3 microMol/Molcreat.
      No statistical difference was found in relation to smoking habits. Workers with
      GSTT1 null genotype had higher 1-OHP levels than those with wild type (p = 0,06).
      CONCLUSIONS: The levels of biomarker of internal dose reflect a critical exposure
      to PAH in the coke-oven plant. Further observations are needed to better
      investigate the role of GSTT1 on the 1-OHP levels.

PMID- 16646260
TI  - [Cancer risk for coke-oven workers in the Taranto steel plant].
AB  - Taranto coke oven batteries create a carcinogenic risk because of workers'
      exposure to PAHs, benzene and asbestos. Because of the vicinity to the city and
      the inadequacy of measures of pollution control, a risk also exists for the
      general population. Although the issue of environmental reclaim had been
      addressed by a specific law (DPR 23.04.1998), the solution to close the oldest
      batteries had been adopted through and enforced by the city administration and
      the Court. However, a recent agreement between ILVA and the Apulia Regional
      Administration has allowed to restart the use of some ovens, after simple
      revamping.

PMID- 16646261
TI  - [Air quality assessment in an urban-industrial area: the Taranto case study].
AB  - OBJECT: The chemical-physical characterization of suspended particulate matter
      and particulate deposition, heavy metals and benzo[a]pyrene, found in the town of
      Taranto and the nearby industrial area (steelworks, cement production, refinery).
      DESIGN: Atmospheric deposition Bulks, air of High Volume (HV) samplers equipped
      with PM10 probe and total suspended particulate matter samplers were used.
      SETTING: 4 sites of monitoring in different urban areas: two of them close to the
      cokery, one near the school, and the last one in the town of Statte (Taranto).
      MAIN OUTCOME MEASURES: Determination of suspended and deposition particulate
      matter concentration, further determination of heavy metal concentration in the
      suspended and deposition particulate matter, and determination of BaP
      concentration. RESULTS: Data evidenced that in the site of Tamburi Cemetery (near
      the cokery) suspended particulate matter PM10 concentrations vary with the
      different seasons (warm period: 67 microg/m3, cold period: 39 microg/m3). Lead
      concentrations are lower than the national limit (0,5 microg/m3); for those heavy
      metals not yet regulated by law, values are comparable with other industrial
      areas. Deposition particulate matter concentrations found nearby the steelworks
      (warm period: 699 mg/m2d, cold period 575 mg/m2d), vary in each different
      monitoring site. In the town of Statte (Taranto) the concentrations found are:
      236 mg/m2d in the warm period, and 154 mg/m2d in the cold period. BaP
      concentrations for PM10 found in the area of Tamburi near the cookery are the
      following: 1,9 ng/m3 in the warm period, and 2,6 ng/m3 in the cold period.
      CONCLUSION: A very compromised situation is found in the area under study as
      regard air quality, especially the particulate matter in its different fractions
      and its content of organic and inorganic pollutants.

PMID- 16646262
TI  - [Geographical study on lung cancer mortality among residents in the neighbourhood
      of the coke plant in Piombino].
AB  - OBJECTIVES: To evaluate a possible risk of lung cancer related to environmental
      pollutants in the population living in Piombino, Italy in the neighborhood of the
      local coke plant. DESIGN: Geographical study. SETTING AND PARTICIPANTS: Lung
      cancer deaths occurred in 1986-2000 in residents in Piombino were included in the
      study. MAIN OUTCOME MEASURES: Observed and expected number of cases for each
      census unit were computed using 4 different case distributions by residence in
      the area: at the time of death, 10 years before death, 15 years before death, and
      the longer residence in Piombino. For each census unit, the expected cases of
      male lung cancer death in 1986-2000 were calculated using the cause-, sex- and
      age-specific mortality rates of the entire area, obtained with the four case
      distributions. Data was analyzed and adjusted for an index ofsocial deprivation,
      using the Stone conditional test. RESULTS: A significant excess risk of lung
      cancer mortality, decreasing with distance from the plant, was observed only when
      the cases experiencing their longer residence in Piombino were included in the
      analysis. CONCLUSIONS: Smoking habits and occupation are the most important risk
      factors, nevertheless environmental pollutants might have played an additional
      role in the causation of the excess risk observed.

PMID- 16646263
TI  - [A study on mortality around six municipal solid waste landfills in Tuscany
      Region].
AB  - OBJECTIVE: Describing mortality of populations residing in the neighbourhoods of
      selected waste landfill sites and contributing to the definition of their health
      status. DESIGN: Descriptive study of mortality at municipality and aggregated
      municipalities level. SETTING AND METHODS: Mortality from 1995 to 2000 in six
      areas of five provinces of Tuscany Region where municipal and/or hazardous waste
      landfills are located. Areas considered at higher exposure were those including
      municipalities where inhabitants mainly reside within 5 km from selected
      landfills. Comparison was made with rates observed in the five provinces in the
      same period. Statistical comparisons were perfomed using standardised mortality
      ratios (SMR) and bayesian mortality ratios (BMR) adjusted for age. MAIN OUTCOMES:
      Mortality for all causes, groups and specific causes of cancer and non-cancer
      diseases. RESULTS: Statistically significant mortality excesses were found for
      circulatory system and cerebrovascular diseases, for lymphohematopoietic system,
      liver and bladder cancer and non-Hodgkins lymphoma. CONCLUSION: Methods utilized
      have produced preliminary indications on associations between residence in areas
      with landfills and mortality. These excesses, also due to the limitations of
      macrogeographic studies, indicate that further insights at microgeographic level
      are needed.

PMID- 16646264
TI  - [Pleural cancer mortality and compensated cases of asbestosis in Sardinia Region
      municipalities (1980-2000)].
AB  - OBJECTIVE: To his study describes the geographical distribution of pleural cancer
      deaths and asbestosis cases from 1980 to 2000 in Sardinia Region (Italy). For
      both conditions regionwide registration systems have been available for a
      relatively long time and allow the identification of statistically significant
      clusters. DESIGN: For each town we have estimated Standardized Mortality Ratios
      (SMRs) for pleural cancer and Standardized Incidence Ratios (SIRs) for
      asbestosis. Expected cases were estimated from age- and gender specific rates in
      Sardinia. SatScan software was used to identify clusters and to verify their
      statistical significance. SETTING: Sardinia Region (Italy). MAIN OUTCOME
      MEASURES: Standardized mortality and incidence rates respectively for pleural
      cancers and asbestosis cases and territorial clusters. RESULTS: The most
      important cluster of pleural cancer was identified in the area defined by
      Carloforte, Calasetta, Portoscuso and Sant'Antioco municipalities (Southwestern
      Sardinia) with 15 observed cases (p value= 0.003). Other clusters were detected
      in the municipality of La Maddalena (11 observed cases against 1.91, expected p
      value= 0.008) and in Southern Sardinia between Cagliari and Sarroch (p value=
      0.018). The town of Marrubiu is clearly the most important cluster (p value= 0.
      001) with 6 asbestosis cases in the period. CONCLUSIONS: These results indicate
      the urgency of the epidemiological surveillance of asbestos related diseases in
      Sardinia. The active search for incident cases of malignant mesothelioma in the
      whole Region and the analysis of modalities of asbestos exposure (according to
      national guidelines) is an indispensable tool for the primary prevention of
      occupational, environmental and domestic exposures from unknown asbestos sources
      of contamination.

PMID- 16646265
TI  - [Serpentine and amphiboles in Calabria: preliminary results of a monitoring
      programme in the general environment and in the workplace].

PMID- 16646266
TI  - [An intervention on the coke-oven at the siderurgical plant in Genoa].
AB  - OBJECTIVE: To assess the personal exposure of workers employed at the coke-oven
      in a steel plant in Genoa. DESIGN: Definition and implementation of a set of
      measurements for the environmental quality for the determination of PAH and
      benzene by means of personal sampling. Urinary determination of the metabolic
      substances given by benzo(a)pyrene and benzene was implemented for workers in
      different areas. Air pollution control was implemented by the firm during the
      years 1997, 1998, 1999 and 2001. Operative ways and sampling methods were
      previously discussed by our Operational Unit of Occupational Health and Safety
      Control (UO PSAL) together with the steel plant and its consultant Clinica del
      lavoro Luigi Devoto. MAIN OUTCOME MEASURES: First environmental pre-screening of
      personal exposure to the pollutant, March to April 1997; first campaign of
      environmental and biological measurements, March 1998; second campaign of
      measurements, February to October 1999 and March 2001. RESULTS: The findings
      showed that among all workers, some groups were more exposed to PAH or benzene:
      "covers" employees, "change" employees, "loading" employees, "refrigeration and
      condensation" employees. REMARKS: Relative shortage of scientific data,
      particularly with regards to the correlation risk/damage; our office operators
      were unable to collect parallel samples in order to validate results of
      environmental and biological analysis because of some local problems; problems in
      maintaining effectively the corrective actions taken; omissions and lack of
      standards in the process used for recording exposures. Lack of awareness, on the
      workers side, on their "right to know" about personal risk. Importance of a
      technical discussion, promoted by the Genoa Province Administration, intended for
      the exchange of information, for providing support to decisions, for comparing
      opinions about the effectiveness of the implemented precautionary measures and
      for interpreting results. The following interventions were carried out: revision
      of job procedures, job methods and Risk Assessment Document; training and
      information about the employees' risk, edited by the firm's Service for
      Prevention and Protection (SPP) and by a physician indicated by the firm; PPE
      (Personal Protective Equipment), revision by the SPP.

PMID- 16646267
TI  - [Identification of polycyclic aromatic hydrocarbons and benzene sources: the
      Genoa-Cornigliano experience].
AB  - OBJECTIVE: To identify PAH and benzene sources in an industrial area in Genoa,
      Italy. DESIGN: Since 1994, airborne concentrations of benzo(a)pyrene (BaP) and
      benzene and wind directions have been monitored in Genoa, near a steel factory
      operating very close to urban residences. The coexistence in the area of
      different potential sources (traffic, domestic heating, coal power plant,
      airport, sea transport) suggested to develop methods in order to identify main
      polluting sources. Correlations of pollutant concentrations with wind directions
      during sampling were used to locate main sources, and differences in PAH chemical
      composition and toluene/benzene ratio were used to identify the most relevant PAH
      and benzene source: the coke-oven, operating inside the steel factory. RESULTS:
      Results demonstrated high concentrations of BaP (annual mean: 8 ng/m3) and
      benzene (annual mean: 15 microg/m3). CONCLUSION: Significant decrease of
      pollution (BaP: 0,2 ng/m3, benzene: 2 microg/m3) after the coke-oven closure,
      confirmed our hypothesis.

PMID- 16646268
TI  - [Health conditions of the general population living near a steel plant].
AB  - OBJECTIVE: To evaluate the health conditions (period 1986-2003) of the residents
      in Cornigliano, a district of Genoa (Italy), exposed to air pollution produced by
      a steel plant with coke-ovens. MATERIALS AND METHODS: Three epidemiological
      investigations were performed: on all mortality causes; on tumors incidence; on
      hospitalizations for respiratory diseases. The studies are based on the Regional
      Mortality Registry, the Ligurian Tumor Registry and the regional hospital
      discharge records. We calculated both the standardized mortality (SMR) and
      incidence (SIR) ratios with 95% confidence limits, and we have compared the
      hospitalization rates in two Cornigliano subareas with different pollution
      levels; the "rest of Genoa" represents the general reference. RESULTS: In
      Cornigliano the total mortality is statistically higher among males (SMR 123; n.
      1684) and females (SMR 148; n. 2160); in particular all tumours, prostate, brain
      and emolymphopoietic system were significantly higher among males, while colon
      rectum and NOS intestine tumours were higher among females. SMRs were
      statistically higher in both genders for degenerative illnesses of the nervous
      central system, brain circulatory disorders and liver cirrhosis; only in males
      for respiratory tract illnesses and in females for myocardial heart attacks. The
      incidence has increased to a statistically significant extent among males for all
      cancer sites (SIR 110; n. 821), and for larynx, brain and emolymphopoietic system
      tumours. Hospitalizations for respiratory illnesses appear to be higher in the
      most polluted area among males (age 0-14), and decreased after closing the coke
      oven plant (2002). CONCLUSIONS: Results of these studies suggest that air
      pollution in Cornigliano may have a role on populations health conditions.

PMID- 16646269
TI  - [Occupational exposure to antineoplastic drugs in a hospital setting: biological
      and environmental monitoring].
AB  - OBJECTIVE: To estimate the occupational exposure of hospital personnel handling
      antineoplastics drugs using a highly sensitive and specific analitycal method in
      biological and environmental samples. DESIGN: To develop analitycal methods for
      the biological and environmental monitoring of more than one substance. SETTING:
      Five departments of the Policlinico Sant'Orsola-Malpighi (Bologna, Italy)
      involved in the preparation and administration of antineoplastic drugs.
      PARTICIPANTS: 50 nurses handling antineoplastics drugs. MAIN OUTCOME MEASURES:
      Evaluation of the occupational exposure of hospital personnel handling and
      administering anticancer drug cocktails. RESULTS: 19 of 50 subjects were positive
      to biological monitoring. Three were positive for MTX only, 11 for CP only and 5
      subjects were positive for both. Urinary MTX levels ranged from 0.3 to 2.0 ppb,
      CP ranged fom 0.06 to 10.0 ppb. Wipe tests showed a higher contamination on the
      hoods working tray (where drugs are prepared), suggesting that the organization
      layout can affect the surface contamination level. Samples from each department
      resulted positive for at least one of three drugs. CONCLUSIONS: The analytical
      methods developed allow sensitive and specific determination of indicators of
      internal and external dose. Biological monitoring is of primary importance for
      assessing the real espoxure of hospital personnel during the preparation and
      administration of the drugs. Environmental monitoring stresses the importance to
      observe the Guidelines for standard operating procedures and the importance of
      protective disposables to reduce exposure and the associated health risk.

PMID- 16646270
TI  - [Biomonitoring of nurses occupationally exposed to antineoplastic drugs: the
      IMEPA Project].
AB  - OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess
      and minimize long term risks in hospital nurses exposed to antiblastic drugs.
      DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in
      Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed
      subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42
      females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary
      markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic
      biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S
      G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency
      in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation
      ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary
      antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP).
      No statistically significant differences were observed in all the considered
      biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring
      study doesn't evidence any early significant effect associated to the exposure to
      antiblastic drugs.

PMID- 16646271
TI  - Healthy living among seniors.
AB  - OBJECTIVES: This article investigates good health among Canadian seniors in
      relation to health behaviours and psychosocial factors. DATA SOURCES: Data are
      from the 2003 Canadian Community Health Survey and the 1994/95 through 2002/03
      National Population Health Survey, household components. ANALYTICAL TECHNIQUES:
      Multiple logistic regression modeling was used to study associations between
      being in good health and behavioural risk and psychosocial factors in 2003.
      Proportional hazards modelling and logistic regression were used to examine
      health-related characteristics and psychosocial factors in relation to
      maintaining and recovering health. MAIN RESULTS: Seniors who exercised
      frequently, had a body mass index in the normal range, were high consumers of
      fruit and vegetables and moderate consumers of alcohol were more likely to be in
      good health. Low levels of stress and feeling connected to the community were
      also associated with good health. Healthy behaviours were related to maintaining
      good health over time, as well as increased likelihood of recovery. These
      findings persisted when controlling for socio-demographic factors and chronic
      conditions.

PMID- 16646272
TI  - Dependency, chronic conditions and pain in seniors.
AB  - OBJECTIVES: This article presents the prevalence of dependency and selected
      chronic conditions among Canadians aged 65 or older living in households.
      Associations between chronic conditions and dependency in activities of daily
      living (ADL) and instrumental activities of daily living (IADL) are examined.
      DATA SOURCE: Estimates are based on data from the 2003 Canadian Community Health
      Survey. ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate the
      prevalence of ADL/IADL dependency and chronic conditions. Associations between
      chronic conditions and dependency were studied using multiple logistic regression
      models. MAIN RESULTS: The prevalence of ADL/IADL dependency and chronic
      conditions increased with age. IADL dependency was more common than ADL
      dependency. When chronic pain was taken into account, associations between ADL
      dependency and arthritis/rheumatism, diabetes and urinary incontinence were no
      longer significant, and the association between IADL dependency and diabetes lost
      significance. Regardless of chronic pain, Alzheimer's disease or other dementia
      and the effects of stroke were significantly related to dependency.

PMID- 16646273
TI  - Seniors' health care use.
AB  - OBJECTIVES: This article describes the use of health care by Canada's senior
      population: consultations with selected health care providers, medication use,
      hospitalization and home care. DATA SOURCES: Data are from the 2003 Canadian
      Community Health Survey and the 2002/03 Hospital Morbidity Database. ANALYTICAL
      TECHNIQUES: Cross-tabulations were used to estimate the proportion of seniors who
      consulted health care professionals, took medications, were hospitalized, and
      used home care. Linear and multivariate logistic regression models were used to
      examine associations between health and the number of physician consultations in
      the past year, the number of medications taken in the past month, and
      hospitalization and home care use in the past year. MAIN RESULTS: In 2003, nearly
      90% of seniors reported that they had consulted a general practitioner or family
      doctor in the past year, 92% reported taking at least one type of medication in
      the past month, 14% had been hospitalized in the past year and 15% had received
      home care in the past year. Chronic conditions, poor health and severe injury
      were strongly associated with health care use. In multivariate analysis, socio
      economic status was generally not related to seniors' use of health care
      services.

PMID- 16646274
TI  - Successful aging in health care institutions.
AB  - OBJECTIVES: This article explores factors associated with positive self-perceived
      health among Canadian seniors who live in health care institutions. DATA SOURCE:
      Cross-sectional and longitudinal data are from the institutional and household
      files of the National Population Health Survey (NPHS). ANALYTICAL TECHNIQUES:
      Prevalence rates of positive self-perceived health were estimated using 1996/97
      cross-sectional data from the NPHS. Logistic regression models were used to
      identify factors associated with positive self-perceived health. With four cycles
      of longitudinal data, the relationship between positive self-perceived health and
      mortality was explored using survival analysis. MAIN RESULTS: In 1996/97, 43% of
      the institutional population aged 65 or older reported positive self-perceived
      health. Institutional residents with positive self-perceived health had a lower
      risk of mortality. The odds of positive self-perceived health were higher for
      those who were usually free of pain and were independent. Participation in social
      and recreational activities and having a close relationship with at least one
      staff member of the institution were associated with positive self-perceived
      health.

PMID- 16646275
TI  - Predictors of death in seniors.
AB  - OBJECTIVES: This article updates information on the leading causes of death for
      people aged 65 or older, and examines factors associated with death in seniors
      over an eight-year period. The analysis focuses on psychosocial factors-
      psychological distress, financial and family stress--in relation to mortality.
      DATA SOURCES: Data are from the Canadian Mortality Database and the 1994/95 to
      2002/03 National Population Health Survey (NPHS), longitudinal file. The NPHS
      sample analysed contains records for 955 men and 1,445 women. ANALYTICAL
      TECHNIQUES: Death certificate information for 2002 and Census population
      estimates were used to calculate death rates and rank causes of death. NPHS data
      were cross-tabulated to examine selected characteristics reported in 1994/95 in
      relation to vital status (dead or alive) by 2002/03. Cox regression was used to
      calculate hazards ratios for psychological distress, financial and family-related
      stress in relation to subsequent mortality, while controlling for the effects of
      age, chronic diseases, and other potential confounders. MAIN RESULTS: In senior
      women, psychological distress in 1994/95 was positively associated with mortality
      over the next eight years, even when controlling for the effects of other
      variables. The statistical significance of this relationship in senior men
      disappeared when controlling for chronic conditions.

PMID- 16646276
TI  - Homogeneity of the 18 QuickSIN lists.
AB  - The purpose of this study was to determine the list equivalency of the 18
      QuickSIN (Quick Speech in Noise test) lists. Individuals with normal hearing (n =
      24) and with sensorineural hearing loss (n = 72) were studied. Mean recognition
      performances on the 18 lists by the listeners with normal hearing were 2.8 to 4.3
      dB SNR (signal-to-noise ratio), whereas the range was 10.0 to 14.3 dB SNR for the
      listeners with hearing loss. The psychometric functions for each list showed high
      performance variability across lists for listeners with hearing loss but not for
      listeners with normal hearing. For listeners with hearing loss, Lists 4, 5, 13,
      and 16 fell outside of the critical difference. The data from this study suggest
      nine lists that provide homogenous results for listeners with and without hearing
      loss. Finally, there was an 8.7 dB difference in performances between the two
      groups indicating a more favorable signal-to-noise ratio required by the
      listeners with hearing loss to obtain equal performance.

PMID- 16646277
TI  - The effects of venting and low-frequency gain compensation on performance in
      noise with directional hearing instruments.
AB  - The present study investigated the effects of gain compensation and venting on
      front-to-back ratios (FBRs), speech understanding in noise, and acceptance of
      noise in 19 listeners with hearing impairment utilizing directional hearing
      instruments. The participants were separated into two groups based on degree of
      low-frequency hearing sensitivity. Subjects were fitted binaurally with Starkey
      Axent II programmable behind-the-ear hearing aids and full-shell earmolds (select
      a-vent). Results demonstrated that gain compensation and venting significantly
      affected FBRs for both groups; however, acceptance of noise was not significantly
      affected by gain compensation or venting for either group. Results further
      demonstrated that speech understanding in noise was unaffected by venting but may
      be improved with the use of gain compensation for some listeners. Clinical
      implications are discussed.

PMID- 16646278
TI  - Evaluation of a second-order directional microphone hearing aid: I. Speech
      perception outcomes.
AB  - This clinical trial was undertaken to evaluate the benefit obtained from hearing
      aids employing second-order adaptive directional microphone technology, used in
      conjunction with digital noise reduction. Data were collected for 49 subjects
      across two sites. New and experienced hearing aid users were fit bilaterally with
      behind-the-ear hearing aids using the National Acoustics Laboratory-Nonlinear
      version 1 (NAL-NL1) prescriptive method with manufacturer default settings for
      various parameters of signal processing (e.g., noise reduction, compression,
      etc.). Laboratory results indicated that (1) for the stationary noise
      environment, directional microphones provided better speech perception than
      omnidirectional microphones, regardless of the number of microphones; and (2) for
      the moving noise environment, the three-microphone option (whether in adaptive or
      fixed mode) and the two-microphone option in its adaptive mode resulted in better
      performance than the two-microphone fixed mode, or the omnidirectional modes.

PMID- 16646279
TI  - Evaluation of a second-order directional microphone hearing aid: II. Self-report
      outcomes.
AB  - This clinical trial was undertaken to evaluate the subjective benefit obtained
      from hearing aids employing automatic switching second-order adaptive directional
      microphone technology, used in conjunction with digital noise reduction, as
      compared to a fixed directional microphone or omnidirectional microphone response
      with the same digital noise reduction. Data were collected for 49 participants
      across two sites. Both new and experienced hearing aid users were fit bilaterally
      with behind-the-ear hearing aids using the NAL-NL1 (National Acoustics Laboratory
      Nonlinear version 1) prescriptive method with manufacturer default settings for
      various signal processing (e.g., noise reduction, compression parameters, etc.).
      During ten days of hearing aid use, participants responded to daily journal
      questions. Subjective ratings for each of the three hearing aid responses
      (omnidirectional, automatic-adaptive directional, and automatic-fixed
      directional) were similar. Overall preference for a microphone condition was
      equally distributed between no preference, omnidirectional, and automatic
      adaptive and/or fixed directional.

PMID- 16646280
TI  - Parents' perceptions of an emerging community-based newborn hearing screening
      program: A case study.
AB  - Thirty-six parents of 106 children (34% response rate) born between March 2000
      and February 2003 retrospectively completed the "Probe of Parents' Perceptions:
      An Early Hearing Detection and Intervention (EHDI) Outcome Measure" (PPP)
      assessing their participation in an emerging community-based newborn hearing
      screening program (NHSP) involving three hospitals in Santa Barbara County,
      California. The PPP, an 11-item questionnaire (in both English and Spanish
      versions), asks parents about their impressions of the explanations of the
      purpose of the screening and of the results, and the referral process. The
      parents were generally positive about all phases of the NHSP; nearly all parents
      said the program had no negative effects on their ability to bond with their
      babies, and they would recommend NHSPs to others. These parents' positive
      impressions in this case study of an emerging community/private practice-based
      NHSP were consistent with those from studies involving parents participating in
      hospital-based programs.

PMID- 16646281
TI  - WHO global strategy for further reducing the leprosy burden and sustaining
      leprosy control activities (Plan period: 2006-2010).

PMID- 16646282
TI  - WHO regional strategy for sustaining leprosy services and further reducing the
      burden of leprosy, 2006-2010.

PMID- 16646283
TI  - National Leprosy Eradication Programme, India. National Action Plan for 2006-07.

PMID- 16646284
TI  - [Dietary habits and early childhood caries intensity among young children].
AB  - The aim of this study was to evaluate the influence of a diet and the feeding
      method on caries intensity among children aged 36-48 months. Dental examination
      was carried out in 255 children and their mothers were asked about child's
      dietary habits. The population checked was divided into three groups: with dmf =
      0, dmf 1-3 and dmf > or = 4. Statistically significant correlation between caries
      intensity and bottle feeding during sleep and frequency of eating cariogenic food
      were shown. Parents of young children should be educated about the influence of
      dietary habits on dental condition.

PMID- 16646285
TI  - [Diagnostic and prognostic significance of serum soluble interleukin 2 receptor
      in children with malignancies].
AB  - The significance of sIL-2R as a marker of pediatric malignancies activity has not
      been evaluated so far. The aim of the study was to determine the clinical role of
      sIL-2R in diagnostics and prognosis in children with neoplasms. MATERIAL AND
      METHODS: The study included 61 children (F/M: 28/33, mean age 7.9 years)
      diagnosed with acute leukemias (ALL - 22, ANLL - 3), malignant lymphomas (HD -
      12, NHL - 6), nephroblastoma and soft tissue sarcomas (Tu Wilms -10, SA- 8).
      Control group consisted of 30 healthy children (F/M: 15/15, mean age 8.8 years).
      Serum sIL-2R was measured by ELISA (DAKO, the Netherlands). RESULTS: Correlation
      of sIL-2R with age was stated thus the results have been presented as
      multiplication of the upper normal range (> 1 xN) determined for the patient's
      age at time of samples collection. Pre-treatment levels of sIL-2R in cancer
      patients were elevated as compared to controls, both regarding the whole
      oncological group and its subgroups: A (ALL + ANLL + NHL), B (HD) and C (Tu Wilms
      + SA) (p < 0.001). 92% of cancer patients presented with elevated levels of sIL
      2R compared to 0% in healthy controls. sIL-2R levels were significantly higher in
      advanced stages of solid tumours and lymphomas and in children with HD and NHL
      with general symptoms and bulky disease presentation. The pre-treatment levels of
      sIL-2R proved to have a great predictive value for overall survival. CONCLUSIONS:
      sIL-2R determination may serve as a useful marker of diagnostics and prognosis in
      different histological types of pediatric malignancies.

PMID- 16646286
TI  - [Prognosis of the bleeding as a complication of percutaneous thick needle biopsy
      of the liver].
AB  - Bleeding after biopsy of the liver (LB) is a rare event, hard to prognose and
      occurs frequently in those cases, when we do not expect it. Bleeding is the main
      reason of complications and deaths subsequent to LB. The aim of the study was to
      prognose the bleeding on the basis of hemodynamic disturbances and clinical
      symptoms occurring just after LB. MATERIAL AND METHODS: The study was performed
      on 145 patients with LB. The blood pressure and heart rate were examined before
      and after procedure of biopsy. In the group of 142 patients without bleeding
      complications, circulating disturbances and clinical symptoms were compared with
      three patients of bleeding subsequent to LB. The patients with bleeding were
      analyzed retrospectively. RESULTS: In the group of patients without bleeding
      complications after LB there was observed statistically significant reduction of
      blood pressure. In 29 cases (46%) bradycardia occurred, in 15 cases (23.8%)
      clinical symptoms of vasovagal syndrome were noticed. Pain at the needle
      insertion site and shoulder pain happened in 15 (10.6%) patients. In one patient
      with low hypotension the pain was intense and localized in the whole abdominal
      cavity. In two cases with bleeding the hypotension occurred in 6th and 7th hour
      with the heart rate 60-70/min and in the third case the massive bleeding led to
      the shock. CONCLUSION: Hemodynamic disturbances including hypotension and
      bradycardia are frequent and difficult to diagnose. Bradycardia does not
      differentiate vasovagal reaction after LB with hypotension caused by bleeding.
      Coincidence of hypotension with abdominal pain indicates the high probability of
      bleeding subsequent to LB. Ultrasound examination of the abdomen is highly useful
      in the confirmation of bleeding complications.

PMID- 16646287
TI  - [Borreliosis--increasing clinical problem].
AB  - Lyme disease (LD) is due to infection with Borrelia burgdorferi (B. burgdorferi).
      We analysed some aspects of epidemiology and clinical manifestation of
      borreliosis. We tried to estimate the efficiency of diagnostic methods and
      treatment. We analyzed medical documentation of 300 patients with LD treated in
      our department between 1993-2001. The diagnosis was made according to Lyme
      Disease Foundation's criteria. Patients suffering from LD were divided into 3
      groups according to stages of the disease. The most frequent manifestation of LD
      was erythema migrans (EM). The number of LD cases had increased during the
      observation time. The exposition to tick-bites was greater during summer and
      early autumn. The great number of patients with EM was observed at the same time.
      Cases of Lyme arthritis (LA), disseminated EM, Lyme carditis (LC) and
      neuroborreliosis represented the group number 2. LA, uveitis and acrodermatitis
      chronica atrophicans (ACA) were diagnosed in the third group of patients.
      Serological markers of B. burgdorferi infection were found in about 50% of cases
      of EM and in each patient in group 2 and 3. Complete recovery after antibiotic
      therapy was observed in every case in early LD and partial one in the late stage.

PMID- 16646288
TI  - [Relationship between nitrogen oxide and the degree of metabolic control of
      diabetes mellitus type 1 in children and adolescents].
AB  - Diabetes mellitus is a disease with early endothelium injury. The most important
      damaging reactions of endothelium may be the abnormal synthesis of nitrogen
      oxide. The aim of the study was the evaluation of nitrogen oxide serum
      concentration in young patients with diabetes mellitus type 1 depending on
      glycated haemoglobin (HbA1c) concentration and parameters of lipoproteins
      metabolism. MATERIALS AND METHODS: Ninety one children and adolescents (36/55,
      M/F) in the age 13.0 +/- 3.5 y., with mean diabetes duration 3.2 +/- 3.8 were
      examined. The control group consisted of 23 healthy volunteers. The degree of
      glycaemic control was taken into account (subgroup I - good glycaemic control
      HbA1c < 6.5%; II--sufficient HbA1c < or = 8.0% and III--poor glycaemic control
      HbA1c > 8.0%). Venous blood was used as a diagnostic material. In all cases
      fasting nitrogen oxide concentration measured indirectly by the level of nitrites
      (NO2-) and nitrates (NO3-) (micromol/L); triglycerides, total cholesterol, LDL
      and HDL cholesterol (mmol/L) were assessed. RESULTS: The mean NO2- (59.20 +/-
      56.77) and NO3- (53.90 +/- 56.63) concentrations were the highest in subgroup III
      (HbA1c- 9.72 +/- 1.21; T-Ch 5.40 +/- 1.04; TGL 2.11 +/- 1.54; LDL-Ch 3.07 +/-
      0.91; HDL-Ch 0.97 +/- 0.19) and differed significantly (p = 0.004) from the
      results of patients with good glycaemic control- subgroup I (HbA1c < 6.37 +/-
      0.17; T-Ch 4.6 +/- 1.13; TGL 1.59 +/- 1.74; LDL-Ch 1.64 +/- 0.72; HDL-Ch 1.10 +/-
      0.17) and healthy individuals (p = 0.006). In the subgroup II mean NO2-(42.31 +/-
      23.23) and NO3- (37.28 +/- 22.70) were high too, but statistical significance was
      stated only with subgroup I (p = 0.003) and healthy individuals (p = 0.001). The
      positive correlation (p < 0.005) was observed between NO2- and NO3- concentration
      and diabetes duration, HbA1c and LDL-Ch in all examined patients and in the
      subgroup II between triglycerides and LDL-Ch concentration and negative one with
      HDL-cholesterol. CONCLUSIONS: Obtained results indicate significant correlation
      between examined parameters of metabolic control and nitrogen oxide
      concentration. This confirms the necessity of constant good metabolic control of
      diabetes mellitus.

PMID- 16646289
TI  - [Practical application of proliferation markers' (MIB-1, PCNA, AgNOR) expression
      analysis for differential diagnostics of nodular thyroid lesions].
AB  - In the study authors tried to estimate the diagnostic value ofAgNOR number and
      MIB-1 and PCNA expression in thyreocytes from various pathological lesions, with
      special attention to differential diagnosis of border-line lesions (nodule in
      adenomatus goiter--adenoma--follicular carcinoma). Fifty four thyroid glands were
      examined (10 adenomatous goiters, 20 follicular adenomas, 10 follicular
      carcinomas, 14 papillary carcinomas). Statistical analysis of obtained results
      allows in most cases to differentiate carcinomas from benign nodular lesions. The
      best differentiating factor for border-line lesions (especially differentiation
      between benign nodular lesions, neoplasms, nodules in adenomatous goiter adenomas
      and adenomas carcinomas) has turned out to be MIB-1. PCNA expression has differed
      significant between adenomatous goiter and follicular carcinoma and between
      adenoma and both carcinomas. AgNOR number has only helped in differentiation
      between nodules in adenomatous goiter and follicular carcinoma - correlations for
      other lesions have not been statistically significant.

PMID- 16646290
TI  - [The results of cytogenetic and molecular genetic examinations in 35 couples with
      primary sterility].
AB  - The causes of primary sterility are complex and frequently difficult to
      elucidate. Cytogenetic anomalies are responsible for sterility in 5-10% infertile
      couples. OBJECTIVES: Analysis of genetic background of primary sterility in 35
      infertile couples. MATERIALS AND METHODS: 72h cultures of peripheral blood
      lymphocytes, GTG and CBG banding, fluorescence in situ hybrydization (FISH) with
      whole chromosome painting (WCP) probes. Karyotype analysis was performed in each
      patient out of 35 infertile couples referred to genetic counsel. SRY and CFTR
      gene mutation analysis by PCR was performed in all men with abnormal sperm.
      RESULTS: Chromosome aberrations were found in 6 couples. Klinefelter syndrome
      (47,XXY) was disclosed in 2 men. Isochromosome i(Xq) was found in 1 woman. The
      structural balanced translocations were found in 2 men; t(15;16)(q13;p13.3),
      t(1;19)(p35;q13.3) and a robertsonian translocation t(14;21)(q10;q10) in one. All
      men with chromosome aberrations had sperm anomalies: oligozoospermia,
      astenozoospermia, cryptozoospermia or azoospermia. There was a CFTR mutation,
      deltaF508, in one man and no SRY mutation in molecularly examined men with sperm
      abnormalities. CONCLUSIONS: In couples with primary sterility mainly the men are
      carriers of chromosome aberrations (CA). Because of 17.14% risk of the presence
      of chromosome aberrations in these couples, cytogenetic analysis should be an
      obligatory element of infertility diagnosis.

PMID- 16646291
TI  - [Analysis of cerebrovascular risk factors in patients with stroke treated in the
      stroke unit].
AB  - Stroke is one of the major public health problems worldwide. Determining the
      cerebrovascular risk factors (RF) is very important in the efforts of primary and
      secondary stroke prevention. The aim of the study was to establish the frequency
      of RF in patients with ischaemic (IS) or haemorrhagic stroke (HS) hospitalized in
      the stroke unit in the Department of Neurology of the Silesian Medical University
      from August 2000 to June 2002. We analysed data of 229 patients (29 with HS and
      200 with IS). Functional outcome was evaluated by use of modified Rankin scale,
      Barthel Index and Scandinavian Neurological Stroke Scale at discharge.
      Statistical analysis was performed with Student's t-test, coefficient of
      correlation and multivariate logistic regression. 94.8% (n = 217) of all the
      patients had one or more RF. The most common RF were: hypertension (78.2%),
      coronary heart disease (54.2%), obesity (29.2%), diabetes mellitus (24.8%) and
      dyslipidaemia (24%). No correlation between the number of RF and functional
      outcome at discharge was observed. Cigarette smoking (p < 0.01) and alcohol abuse
      (p < 0.005) were more frequent in young patients (< 55 years). Previous ischaemic
      stroke was more common in older patients (>55 years). In male patients cigarette
      smoking and alcohol abuse were found more frequently than in female (p < 0.001).
      The mortality in examined patients was 22.2% (20.4% in patients with IS and 45.8%
      with HS). Male gender (p < 0.05), history of previous cardiac infarction (p <
      0.05) and previous ischaemic stroke (p < 0.01) were associated with increased
      mortality. The other variables studied did not show significant differences.

PMID- 16646292
TI  - [Evaluation of upper cervical spine injury (C1-C2) with computed tomography].
AB  - Cervical spine injuries are common and essential diagnostic problem. Diagnostic
      imaging is necessary for proper and effective treatment. Helical computed
      tomography (CT) and plain radiography are the basic diagnostic methods in
      cervical spine injuries. The purpose of this work was the comparison of CT
      examination of the upper cervical spine (CI-C2) with patients' clinical state.
      Twenty four patients (17 men and 7 women) were introduced into the study. The
      most common cause of cervical spine injuries were car accidents (48.5%). CT
      examination was performed in all patients. Six patients (25%) had multilevel
      injury, localized at C1-C2 level and in the lower part of cervical spine. The
      main pathology diagnosed by CT in the studied group was rotatory subluxation
      (66.6%). Eight patients (33.3%), with rotatory subluxation did not present any
      abnormalities in neurological examination performed immediately after the
      admission to the hospital. C1 and/or C2 fractures were diagnosed in 11 patients
      (45.8%), in some cases (in 3 patients - 12.5%) they were accompanied by rotatory
      subluxations. CT examination is the basic technique of diagnostic imaging in a
      case of cervical spine injuries. It enables quick, accurate and precise
      evaluation of bone structures and surrounding soft tissues. CT also enables
      multiplanar imaging and 3-dimentional imaging.

PMID- 16646293
TI  - [Serum androgens concentrations in women with idiopathic premature ovarian
      failure].
AB  - In this paper we investigated androgen serum concentration in women with
      idiopathic premature ovarian failure (POF). The research was conducted in 30
      patients with POF and results of analysis were compared to 15--women after
      surgical oophorectomy and to groups of women matched in radomization:
      postmenopausal women (35 subjects) and healthy fertile women (27 subjects). We
      established that subjects with POF showed about 50% lower concentration of free
      testosterone compared to women who had undergone natural menopause and to fertile
      controls. Androstendione concentration was similar in all researched groups and
      was significantly lower than in fertile controls. Both women with POF and
      postmenopausal subjects showed lower concentration of dehydroepiandrosterone
      sulfate (DHEA-S) compared to fertile women. Analysis of the results allowed us to
      come to conclusion that POF women, like women after surgical oophorectomy, suffer
      from relative androgen deficiency.

PMID- 16646294
TI  - [Time to diagnosis as an index of efficiency of the health care system--lymphoma
      study].
AB  - In the year 1999 the reform of the health care system was introduced in Poland.
      It was probably the biggest among many changes that the polish health care system
      underwent in the years 1990-2002. Still there are only a few unbiased analyses
      trying to assess possible influence of those changes on the function of the
      system. One of the ways may be the analysis of time to diagnosis. The aim of our
      work was to analyze time to diagnosis in lymphoma, and see the possible influence
      of changes in the system on it. The average time from the onset of the first
      symptoms to the contact with a general practitioner was 70 days (range 3 to 240
      days) for all of the analyzed groups of patients. The reduction of time to
      diagnosis was observed during the years 1990-2002. The biggest change was present
      in the group of patients that presented with unspecific symptoms e.g. weight
      loss, fever (reduction of mean time to diagnosis from 47 days to 32 days, p <
      0.05). The changes were due to the constant slow changes that are introduced in
      the function of health care system (improvement of qualifications of the doctors,
      better diagnostics techniques), and could not be contributed to the reform. In
      the group of patients with an enlargement of lymph nodes on presentation, we were
      not able to observe any changes in time to diagnosis.

PMID- 16646295
TI  - [Usefulness of breath actuated devices in asthmatic children with bronchial
      obstruction].
AB  - Clinical efficacy of breath actuated devices depends on value of peak inspiratory
      flow (PIF). Therefore the aim of our study was to assess PIF Rate (PIFR) in
      asthmatic children with bronchial obturation (FEV1%FVC < lower limit of normal).
      Thirty five children aged (average) 11.5 years participated in the study. PIFR
      was obtained with InCheck (Clement Clark, UK) with resistance valves for
      Turbuhaler, Discus, Easi Breathe and Autohaler inhalers, then peak inspiratory
      flow was assessed spirometrically (LungTest 1000, MES SJ, Poland). Maximal value
      of PIFR (PIFRmax=120 l/min) was obtained by 24 (69%) children for Easi Breathe, 3
      (9%) children for Autohaler, 2 (6.5%) children for Discus, for Turbuhalera none
      of the children reached PIFRmax, differences in assessing PIFRmax were
      statistically significant (p < 0.05). However, all the children were able to
      generate minimal and optimal PIFR for all inhalers. There were no correlation
      between the degree of bronchial obstruction and PIFR values, but significant
      correlation was found between spirometric PIF and PIFR for different devices. All
      four tested inhalers can be used by children with bronchial obstruction, and the
      highest PIFR (as well as most frequently maximal PIFR) is obtained with Easi
      Breathe inhaler.

PMID- 16646296
TI  - [Serum glycosaminoglycans in Graves' disease patients].
AB  - The aim of the study was to determine the blood serum sulfated glycosaminoglycans
      (GAGs) and hyaluronic acid (HA) concentration of Graves' disease patients before
      treatment and after attainment of the euthyroid state. The study was carried out
      on the blood serum obtained from 17 patients with newly recognised Graves'
      disease and from the same patients after attainment of the euthyroid state.
      Graves' patients had not any clinical symptoms neither of ophthalmopathy nor
      pretibial myxedema. GAGs were isolated from the blood serum by the multistage
      extraction and purification using papaine hydrolysis, alkali elimination, as well
      as cetylpyridium chloride binding. Total amount of GAGs was quantified by the
      hexuronic acids assay. HA content in obtained GAGs sample was evaluated by the
      ELISA method. Increased serum concentration of sulfated GAGs in non-treated
      Graves' disease patients was found. Similarly, serum HA level in untreated
      patients was significantly elevated. The attainment of euthyroid state was
      accompanied by the decreased serum sulfated GAGs level and by normalization of
      serum HA concentration. In conclusion, the results obtained demonstrate that the
      alterations of GAGs metabolism connected with Graves' disease can lead to
      systemic changes of the extracellular matrix properties.

PMID- 16646297
TI  - [Hydrogen sulphide water balneum effect on erythrocyte catalase activity in
      patients with rheumatoid arthritis--in vitro study].
AB  - The aim of the study was to investigate, in vitro, hydrogen sulphide water (HSW)
      balneum effect on erythrocyte catalase activity in patients with rheumatoid
      arthritis. Erythrocytes from twenty nine consecutive patients with rheumatoid
      arthritis (11 men, 18 women) aged 54 years were obtained. The control group
      comprised of 30 healthy subjects with a mean age of about 40 years. Patients with
      rheumatoid arthritis were subdivided into two groups twice: with active disease
      (18 patients) and in remission (11 patients), and secondly into patients
      receiving (21 subjects) and not receiving (8 subjects) non-steroidal anti
      inflammatory drugs. For erythrocyte catalase activity evaluation, method of Beers
      and Sizer was used. Catalase activity was assessed after 5, 10, 15, and 20
      minutes erythrocytes incubation with HSW. The mean baseline erythrocyte catalase
      activity (to) was in rheumatoid arthritis patients of about 7.79 +/- 1.39 U/gHb
      and was significantly higher than in the control group: 6.96 +/- 2.68 U/gHb (p <
      0.05). After 5 minutes incubation with HSW (t5) erythrocyte catalase activity
      increased, in rheumatoid arthritis patients to 8.21 +/- 1.77 U/gHb, after 10
      minutes (t10) was 8.14 +/- 2.25 U/gHb, in control group: 7.58 +/- 2.50 U/gHb and
      7.68 +/- 3.22 U/gHb, respectively. However the difference was not statistically
      significant. After 20 minutes of incubation (t20) erythrocyte catalase activity
      was the highest in the patients with active rheumatoid arthritis (8.33 +/- 1.96
      U/gHb) and differed significantly from the patients in remission (6.69 +/- 1.27
      U/gHb) and from patients not receiving non-steroidal anti-inflammatory drugs
      (6.04 +/- 1.08 U/gHb). In rheumatoid arthritis patients erythrocyte catalase
      activity was higher when compared with control group and increased during
      incubation with HSW. It seems HSW balneum produce an antioxidant effect on
      erythrocyte status in patients with rheumatoid arthritis.

PMID- 16646298
TI  - [Benzylpenicillin as an allosteric effector].
AB  - Benzylpenicillin (penicillin G) is a model drug for studies of drug-protein
      biochemical interactions. Furthermore the literature indicates that
      benzylpenicillin and protein conjugation is a universal phenomenon:
      benzylpenicillin is known to readily conjugate to proteins-serum albumin,
      globulin and others peptides to modify space structure and electrophoretical
      properties. The aim of the study was to test if the benzylpenicillin is an
      allosteric effector. Serum benzylpenicillin concentration in geometric
      progression was used. Then acid phosphatase (AcP), alanine aminotransferase
      (AIAT) activity and international normalized ratio (INR) was tested. Although
      benzylpenicillin influences AcP and INR, only AcP activity is directly
      proportional to the benzylpenicillin concentration (Pc): change of AcP activity
      was the derivative of Pc in 76% (R2 = 0.7635). Furthermore, the benzylpenicillin
      appears to be uncompetitive inhibitor of acid phosphatase (inhibitory constant Ki
      = 95.67M; Vmax = 34.843 nKat). On the contrary no effect of AIAT activity was
      observed. Unexpectedly INR was modified in irregular manner: in some
      concentrations of benzylpenicillin INR was over 25% lower than in control probe
      (INR approximately 0.6 vs. 0.82). Unfortunately INR > 6.5 is accepted as an early
      indicator of poor prognosis in fulminant hepatic failure. This phenomenon may be
      useful in sepsis as a prevention of disseminated intravascular coagulation (DIC).
      These data indicate that high benzylpenicillin concentration may be the cause of
      artifacts. The facts allow of interpretation that the allosteric effect of
      benzylpenicillin on enzymes activity is a possible mechanism of unpredictable
      adverse drug reactions (i.e. intolerance).

PMID- 16646299
TI  - [Cachexia in chronic pulmonary obstructive disease].
AB  - Weight loss is a characteristic feature of chronic obstructive pulmonary disease
      (COPD) and a negative, independent predictor of outcome. It is a consequence of a
      misbalance between protein synthesis and breakdown resulting from increased
      energy requirement unbalanced by dietary intake. A depletion of fat-free mass is
      seen, especially in muscles (up to 60% of their mass) and leads to the loss of
      their power and endurance. The impairment of quality of life is very distinct. So
      far, there is no systemic treatment in cachectic patients with COPD, anti
      catabolic treatment by polyunsaturated fatty acid may be of significance but
      needs further investigation.

PMID- 16646300
TI  - [The safety of the antihistamines in dermatoses of pregnancy].
AB  - Pregnancy is frequently complicated by dermatoses, in which antihistamines may be
      potentially used. In fact, none of these drugs currently used has been classified
      by FDA on the basis of controlled human and animal studies as completely negative
      from the point of view of untoward effects in pregnancy. Based on the information
      available to date, in this paper we have attempted to provide rational guidelines
      for the gestational use of H1-receptor antagonists.

PMID- 16646301
TI  - [Pathogenesis of chronic obstructive pulmonary disease. Cellular mechanisms (part
      I)].
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality worldwide. Smoking is considered the major cause of the disease. All
      smokers develop airway inflammation through oxidative stress with macrophages,
      neutrophiles, lymphocytes, eosinophils, NK-cells and mediators involved.
      Macrophages through the activation of Nuclear Factor kappa B (NF.-kappaB) release
      proinflammatory mediators, lymphocyte chemotactic agents and elastolytic enzymes,
      activate neutrophil driven serine proteases and GM-CSF. Neutrophiles release IL-8
      which in turn recruits neutrophils to the airways. In response to cigarette smoke
      lung epithelium may release TNF-alpha, TGF-beta, IL-1beta, GM-CSF, IL-8 reactive
      oxygen species (ROS). Increased number of lymphocyte T CD8+ and CD4+
      subpopulations may lead to lung epithelium cells apoptosis and necrosis through
      perphorines and granzyme-B and TNF-alpha activation. Moreover, increased
      expression of IL-6, IL-10, IL-12, IL-13, and INF-gamma is observed. Authors
      indicate the possibility of new treatment strategies such as: agents directed
      against adhesion molecules, chemokines, phosphodiesterase 4, p38 MAPK, NF.-kappaB
      phosphoinositide-3-kinase gamma, TGF-beta, NOS synthase, serine proteinases and
      matrix metalloproteinases.

PMID- 16646302
TI  - [Reasons for recurrent respiratory tract inflammations in children].
AB  - Respiratory tract inflammations are among the most frequent diseases in children.
      In natural conditions, respiratory tract is constantly prone to environmental
      pathogens. In fighting the respiratory tract infections both non-specific and
      specific: humoral and cellular immune mechanisms, related to mucosa-associated
      lymphoid tissue (MALT), take part. In healthy subjects, the upper respiratory
      tract is affluent in physiological bacterial flora comprising aerobic and
      anaerobic bacteria, some of them potentially pathogenic. In periods of reduced
      immunity they can cause endogenous infections. Contrary to the upper, the lower
      respiratory ways are physiologically sterile. The imbalance between defense
      mechanisms and pathogenity of microorganisms can lead to the development of
      infection. Recurrent respiratory tract inflammations, due to complexity of their
      causes, are a problem of great importance. Early estimation of the etiology of
      recurrent inflammations is particularly crucial, as it allows introduction of
      aimed therapy and prophylactics, thus preventing the child from the development
      of irreversible pulmonary lesions and impairment of physical development.

PMID- 16646303
TI  - [Clinical aspects of hyperbaric oxygenation].
AB  - Authors have presented methods of hyperbaric treatment used in the clinical
      settings. They have commented on the problem of oxygen toxicity, oxygen poisoning
      and indications and contraindications to hyperbaric oxygenation. In spite of side
      effects and possible complications, HBO can be a valuable method of treatment of
      many diseases. This method should be initiated in due time, after proper
      qualification of patients and by using the treatment protocol appropriate for
      every patient.

PMID- 16646304
TI  - [Effects of combined spinal-epidural anesthesia in patients undergoing abdominal
      aorta aneurysms stent-grafting].
AB  - We present the anesthetic combined spinal-epidural management of two patients
      undergoing endovascular abdominal aorta aneurysm stent-graft procedure. Due to
      many concomitant diseases: high blood pressure, chronic pulmonary obstructive
      disease, diabetes and obesity both patients were of high anesthesia risk. With no
      need for abdominal surgical opening, anesthetic muscles relaxation and
      intraoperative ventilatory support, CSEB was a method of choice. Additionally it
      provided sufficient intraoperative and postoperative analgesia with a possibility
      of anesthesia prolongation when needed and decreased the overall risk of
      intraoperative and postoperative cardiac and respiratory complication.

PMID- 16646305
TI  - [Rare case of palatal amyloidosis].
AB  - Amyloidosis first described by Karl Rokitansky in 1842 consists in accumulation
      of pathological protein (amyloid) within both cells and extracellular space. It
      usually develops in the course of a chronic inflammation or some neoplasms. The
      clinical picture depends on the impairment degree of an organ in which amyloid
      accumulates. The diagnosis is based on the cytological examination of the
      material collected by means of biopsy of the subcutaneous fatty tissue and of the
      mucosa of the anal orifice, gums, kidneys or liver etc. In the presented study a
      rare case of amyloidal concrements localised in the palatal region has been
      described. Literature has usually presented amyloidosis localised in the tongue,
      lips, rhino-pharynx and larynx. Amyloidosis localised in the region of the head
      and neck occurs very rarely. In the presented case amyloidal deposition in any
      other site was not reported.

PMID- 16646306
TI  - [Churg-Strauss syndrome--a case report].
AB  - A case of a 58-year-old woman with Churg-Strauss syndrome is reported. After
      therapy with steroids clinical improvements were obtained. The discussion
      concerning the pathogenesis of disease was performed.

PMID- 16646307
TI  - [Perianal abscess in the course of a cervical cancer].
AB  - A case of a 61 old patient with perianal abscess is described. The authors
      present untypical process of disease, treatment and diagnostic procedure leading
      to the detection of primary disease i.e. cervical cancer in IV grade clinical
      advanced. The healing of abscess cavity was reached during treatment. The
      diagnosis was determined on the grounds of unambiguous result of
      histopathological examination. The patient was admitted to the gynecological
      department. Demise happened after three months from admitting to the surgical
      department. The author emphasize the importance of case history, carefully
      physical examination and adequate diagnostic in order to recognize etiology and
      location the abscess and select the optimal method of treatment.

PMID- 16646308
TI  - [A case of polyostotic fibrous dysplasia].
AB  - Fibrous dysplasia (FD) is a benign but slowly progressive disorder of bone in
      which normal cancellous bone is replaced by immature woven bone and fibrous
      tissue. Fibrous dysplasia is a very uncommon disorder and the total number of
      cases is not known. It is usually diagnosed in children and young adults. Some
      patients have only one bone affected (monostotic), whereas other patients have
      numerous bones affected (polyostotic). Multiple affected bones are often found on
      one side of the body. The craniofacial involvement causes very difficult
      therapeutic problem due to localisation and uncontrolled proliferation followed
      by compression, both resulting in facial asymmetry, pain, cranial nerve
      deficiencies, alterations in hearing and loss of vision. Treatment of FD depends
      on the associated symptoms and may include a range of therapies from observation
      to complete surgical excision. We describe a rare case of polyostotic fibrous
      dysplasia with craniofacial localisation associated with the involvement of the
      humerus in a 65-year-old female patient. The first symptoms in the patient were
      noted 4 years ago. The diagnosis was based on clinical examination, X-ray, CT and
      histological examination.

PMID- 16646309
TI  - [Atypical clinical picture of strangulated obturator hernia].
AB  - Strangulated obturator hernia is a very rare condition found almost always in
      elderly, debilitated multiparas usually with concomitant severe chronic
      illnesses. The authors presented a case of a young, 35-years-old woman of normal
      constitution, nullipara, without previous abdominal surgery. This unusual
      clinical picture despite the symptoms of intestinal obstruction caused
      difficulties in the correct preoperative diagnosis. It is the youngest case of
      patient with strangulated obturator hernia described in Polish medical
      literature.

PMID- 16646310
TI  - [Amanita phalloides poisoning as an indication for liver transplantation in three
      family members].
AB  - Amanita phalloides poisoning is one of the most dramatic medical invents. The
      course of the illness may vary from mild to the lethal, with signs of fulminant
      liver insufficiency with coma and multiorgan failure. When hepatic encephalopathy
      (III/IV degrees) occurs the prognosis is very poor. In definite cases the liver
      transplantation is necessary. The authors present severe Amanita phalloides
      poisoning in three family members, who due to fulminant hepatic failure underwent
      liver transplantation. The two of them (son and father) transplanted accordingly
      in fifth and seventh day after poisoning, survived. Mother, in whom
      transplantation started in ninth day after poisoning, died intraoperativel with
      signs of massive hemorrhage, and cardiac arrest.

PMID- 16646311
TI  - [Retroperitoneal fibrosis--possible cause of hypertension].
AB  - The purpose of this study is to show the case of idiopathic retroperitoneal
      fibrosis, which clinically manifests itself as hypertension. The property of this
      disease described for the first time by Ormond is pathological deposition of
      connective tissue in retroperitoneal space. In this particular case hypertension
      develops as the result of renal hypoperfusion and subsequent activation of the
      renin-angiotensin-aldosterone system, caused by hydronephrosis and compression of
      renal vessels by pathologic tissue. The early diagnosis based on computer
      tomography and magnetic resonance provided the possibility of proper treatment.
      However, therapy procedure limited only to hypertension treatment may effect in
      progression of hydronephrosis and renal insufficiency.

PMID- 16646312
TI  - [Methods estimating gallbladder volume].
AB  - An increasing incidence of liver and biliary tract diseases brings about an
      increasing necessity of their precise diagnosis. The procedure of estimation of
      gallbladder volume seems to be useful in ultrasonic examination of gallbladder
      motility and is widely applied in human medicine all over the world. The methods
      estimating gallbladder volume can be divided into two groups. The first group
      comprises the application of rather simple formulas approximating the actual
      gallbladder shape to the given geometric solid. These methods are precise when
      the actual gallbladder shape is at least roughly similar to the approximated
      solid. The second group is more uniform methods since their precision is
      principally not dependent on the gallbladder shape. The aim of this article was
      the description and comparison of more or less known methods ascribed to the both
      groups. Among the methods of the first group, one of the firstly applied and less
      precise methods usually lowering the results is the method approximating the
      gallbladder shape to a cone. More common and precise is the ellipsoid method, but
      this method sometimes also approximates the gallbladder shape not very
      accurately. The other methods approximating the gallbladder shape to a barrel,
      cylinder, sphere, trapezoid or frustum of cone and the modifications of some of
      these methods like the method of cone and ellipsoid, are comparable with the
      ellipsoid method. The planimetric group of the methods can be included into the
      second group and in these methods the calculation of the area of the organ
      longitudinal image is followed by estimation of the organ's volume. Other
      validated methods are: the random points method based on the known group of
      mathematical methods (Monte Carlo) representing practically one ofplanimetric
      methods, the commonly used sum-of-cylinder method and the Simpson method. The
      reported data indicate that Simpson method is currently the most accurate method
      estimating the gallbladder volume while the planimetric and sum-of-cylinder
      methods are believed to be also accurate. The applied method estimating
      gallbladder volume should be selected in the manner that guarantees its possibly
      maximal accuracy.

PMID- 16646313
TI  - Occurrence of extra and anomalous setae on pupal abdominal segment VIII of the
      Dolosus Complex of Culex (Diptera: Culicidae).
AB  - The presence of extra and anomalous setae on abdominal segment VIII of whole and
      the exuviae of pupae of the Dolosus Complex of Culex is reported. Also, seta 10
      VIII in 14 specimens was observed. An anomalous seta 0-VIII is present in a
      single specimen and was observed to be large and have multiple branches.

PMID- 16646314
TI  - The association of Aedes aegypti and Ae. albopictus in Allende, Nuevo Leon,
      Mexico.
AB  - The recent appearance of Aedes Stegomyia albopictus (Skuse) in Nuevo Leon (NL)
      worries health officials. It is a vector of dengue fever in Asia and is more
      resistant to lower temperatures than Ae. aegypti. The objective of this study was
      to learn about some ecological parameters of Ae. albopictus and their association
      with Ae. aegypti, and other culicids in Allende, NL, Mexico, during 1999. Allende
      is a small town close to metropolitan Monterrey, which has 4 million inhabitants.
      The design was random with monthly sampling of 175 ovitraps. Chi-square analyses
      were performed with data of presence, absence, frequency, and relative
      abundances. During the study, the species Culex tarsalis (Coquillet), Cx.
      thriambus (Dyar), Cx. pipiens (Linnaeus), Cx. coronator (Dyar and Knab), Ae.
      albopictus, Ae. aegypti, Toxorhynchites rutilus (Coquillet), and Ae. triseriatus
      (Say) were found. April is the month for large numbers of mosquito species.
      September had the highest populations in positive ovitraps (66.67%), followed by
      July (63.27% of traps). Aedes aegypti was the most abundant (65.13%), followed by
      Ae. albopictus (19.71%). Both Ae. albopictus and Ae. aegypti were found from
      April until December. Aedes aegypti was more abundant than Ae. albopictus, except
      in August, when they were similar (chi2 = 0.197, P < 0.05). We found significant
      association between the presence of both species for every study month (chi2 =
      9.837, P < 0.05), with a contingency coefficient of 0.247. September and November
      were the months having the most mosquitoes in this association. Only considering
      Ae. albopictus, more were found in ovitraps in July (34.6%), followed by
      September (33.3%). However, its presence was not significant throughout the year.
      Of 2 zones, in town and at the river, prevalence indicated that Ae. albopictus
      preferred the river. This mosquito is in its establishment phase in this area and
      requires further studies.

PMID- 16646315
TI  - Gonotrophic cycle and survivorship of Culex quinquefasciatus (Diptera: Culicidae)
      using sticky ovitraps in Monterrey, northeastern Mexico.
AB  - Mark-release-recapture experiments were conducted to determine the length of the
      gonotrophic cycle and rate of survivorship of Culex quinquefasciatus Say in
      Monterrey, northeastern Mexico. A total of 2,352 field-caught Cx.
      quinquefasciatus females were marked and released at 8-12 h postemergence in 2
      field trials. Sticky ovitraps were used to recapture marked gravid females. One
      hundred and ten (4.6%) marked females were recaptured during a 12-day sampling
      period. Recapture rates for the 2 individual trials were 6.4% and 3.5%. The
      length of the gonotrophic cycle, calculated as the average time between the
      initial blood meal and the time of recapture of gravid females, was 2-3 days. The
      first blood-fed mosquitoes were recaptured on the 2nd day postrelease. Gravid egg
      laying females were most commonly recaptured at 2-3 days postfeeding. Daily
      survival estimates for the 2 release dates were of 0.871 and 0.883, respectively.

PMID- 16646316
TI  - Does 1-octen-3-ol enhance trap collections of Japanese encephalitis virus
      mosquito vectors in northern Australia?
AB  - The responses of Japanese encephalitis virus (JEV) mosquito vectors to 1-octen-3
      ol (octenol) and CO2 were evaluated using Centers for Disease Control (CDC) light
      traps at 3 sites in northern Australia. There was no significant difference
      between the number of Culex sitiens subgroup mosquitoes or Cx. gelidus collected
      in CDC light traps baited with either CO2 alone or CO2 + octenol on Badu Island.
      At both mainland locations, using octenol in combination with CO2 significantly
      increased collections of Cx. sitiens subgroup mosquitoes. Collections of
      nontarget species, such as Ochlerotatus spp., Anopheles spp., and Verrallina spp.
      were also significantly increased with the addition of octenol. At all 3
      locations, reducing collections of nontarget mosquitoes by not using octenol
      increased the proportion of Culex spp. collected, thus potentially reducing the
      time and resources required to sort and process collections for JEV detection.
      Our results also indicate that trials into the efficacy of using octenol as an
      attractant should be carried out in each area prior to the implementation of a
      mosquito-based arbovirus surveillance system.

PMID- 16646317
TI  - Ecology of the malaria vector, Anopheles (Nyssorhynchus) marajoara Galvao and
      Damasceno in Trinidad, West Indies.
AB  - The taxonomy and ecology of wild-caught Anopheles marajoara mosquitoes derived
      from rice fields in Frederick Settlement, Trinidad, were studied in the
      laboratory using specimens identified with species-specific random amplified
      polymorphic DNA (RAPD) profiles and recently developed rDNA ITS2 polymerase chain
      reaction methods. Adults were collected using Shannon traps and human bait in 2
      houses over a 1-year period. All mosquitoes collected were taken to the
      laboratory, where they were identified, wing-length measured, and parity rates
      determined using standard methods. In addition, 25 females were blood fed and
      subsequently offered a blood meal every 2 h for a 60-h period. Based on the
      morphological keys and molecular tools used, the presence of An. marajoara is
      confirmed in Trinidad for the first time. Analysis of the seasonal distribution
      of An. marajoara revealed that over 58% were collected during the rainy season.
      The wing length of 660 females measured averaged 2.90 +/- 0.130 mm, with no
      significant differences being observed among the parous and nulliparous females'
      wing sizes (2.90 and 2.92 mm, respectively). In addition, the monthly parous rate
      was not significantly correlated with mean wing-length over time (r = 0.157, df =
      16, P > 0.07). Results from the blood feeding studies showed 85% of females blood
      fed immediately (hour 0) after capture in the field. However, blood feeding
      declined thereafter until 24 h later, when over 40% refed. This study clearly
      identified the presence of An. marajoara in Trinidad and provides information of
      the seasonal abundance and blood-feeding behaviors. These results suggest that
      this species can play a significant role in the transmission of malaria within
      its geographical range in the Neotropics.

PMID- 16646318
TI  - New findings on the developmental process of Ascogregarina taiwanensis and
      Ascogregarina culicis in Aedes albopictus and Aedes aegypti.
AB  - Infection in different stages of larvae of Aedes aegypti and Ae. albopictus with
      Ascogregarina taiwanensis and A. culicis, respectively, revealed that the oocysts
      of Ascogregarina spp. are able to infect any instar and can complete their life
      cycle within 9.5 +/- 1 days. When early instars ingested oocysts, parasite
      development was synchronized to larval-pupal ecdysis and oocyst dissemination
      occurred at the time of adult emergence, oviposition, or both. The parasites also
      developed normally when infecting 2nd, 3rd, and early 4th instars and oocysts
      were released only during oviposition. The parasitic development stopped at the
      gamont stage when oocysts were ingested by late 4th instars (6 days old). The
      release of sporozoites in the midgut of any larval stage started within 45 min of
      oocyst ingestion. About 98% of oocysts of both A. taiwanensis and A. culicis were
      emptied within 2-3 h of their ingestion in their respective hosts. The oocysts of
      both species remained viable on desiccated filter paper stored at 27 degrees C
      and 65 +/- 5% relative humidity, indicating that the oocysts were resistant to
      dryness. The oocysts of A. culicis could survive up to 6 months, whereas those of
      A. taiwanensis survived up to 4 months. These biological characteristics relating
      to parasite development might enhance the distribution of Ascogregarina spp.
      widely in nature and facilitate the species to be considered for biological
      control of Aedes mosquitoes in the future.

PMID- 16646319
TI  - Comparative attractiveness of two chicken breeds to mosquitoes in southern
      California.
AB  - Each transmission season (April-October), mosquito control districts deploy more
      than 2,000 white leghorn hens as sentinels in California's arbovirus surveillance
      program. In 2002, Rhode Island red hybrids were used instead, because of
      insufficient availability of leghorns. Although arboviral seroconversions
      occurred in both breeds, their attractiveness to host-seeking mosquitoes was not
      compared. During August and September 2004, Florida Medical Entomology Laboratory
      traps, each containing 1 hen, were deployed twice weekly at each of 4 fixed
      locations at a southern California wetland area. The breed at each location was
      alternated each trap-night to account for intersite variation in the mosquito
      population. Six chickens of each breed were rotated through the traps to account
      for interchicken variation in mosquito attractiveness. Although the mosquito
      counts varied significantly among trap locations, no significant difference was
      found between the 2 breeds. Sera collected biweekly detected seroconversions to
      Flavivirus in 4 of 6 red and 1 of 6 white chickens, not a statistically
      significant difference. Larger sample sizes or experimental infection of
      different chicken breeds may identify differences in their response to arbovirus
      infection.

PMID- 16646320
TI  - Oviposition preference and egg eclosion in different salt concentrations in the
      coastal malaria vector Anopheles aquasalis Curry.
AB  - Anopheles aquasalis is the main malaria vector in Sucre State, Venezuela. The
      larvae of this species are saltwater tolerant. The effects of different
      concentrations of salt on oviposition preference and egg survival were studied
      under laboratory conditions. Choice experiments with salt concentrations of 0,
      10, 20, 30, and 40% in bottled water were set up for individual adult females and
      the number of eggs laid in each salt concentration was noted. Egg survival, as
      inferred by the number of hatched larvae also was determined for each salt
      concentration. Females preferred to oviposit in freshwater and rejected water
      salt concentrations of 40%, but they were neither attracted nor repelled by water
      with 10-30% of salt. Eggs hatched more quickly in the lower salt concentrations,
      but egg survival was not affected by salt concentrations of up to 20%. Thus,
      female oviposition preference in An. aquasalis determines egg survival.

PMID- 16646321
TI  - Seasonal variations in activity and size of adult females and local distribution
      of larvae for populations of Culex salinarius in the upper coastal zone of
      southeastern Texas.
AB  - Activity of adult female populations of Culex salinarius, as determined by light
      trap collections, was studied in Chambers County, Texas, from June 1988 to July
      1990. Overall, Cx. salinarius was the predominant species collected by light
      traps. Female Cx. salinarius were present in every month of the 2-year study
      period, with spring peaks in April and May and autumn peaks in September and
      October. Traps set in southern and central areas collected more specimens of Cx.
      salinarius than did those located in western areas, especially during spring,
      summer, and fall seasons. Females with longest wing lengths were collected in
      cooler winter months and those with shortest wing lengths were collected in warm
      summer months. Females having the longest wings tended to be collected at trap
      sites in coastal marsh areas of Chambers County, irrespective of when collections
      were made. Dipper samples taken on a monthly basis from fixed sites in upland
      agricultural and coastal marshland areas indicate that larvae of this species
      were present at more sampling sites during cooler months than in the warmest
      months of June, July, and August.

PMID- 16646322
TI  - Artificial bloodfeeding of Anopheles stephensi on a membrane apparatus with human
      whole blood.
AB  - The purpose of this study was to rear large numbers of Anopheles stephensi (Lis.)
      by artificial feeding with human whole blood in an insectary. An artificial
      membrane, bloodfeeding technique was evaluated for An. stephensi using the
      insectarium's strain in Iran. Parafilm "M" and human whole blood were
      satisfactory as a feeding membrane and as a source of nourishment, respectively.
      Comparison of feeding rates and different ages were fluctuated in rearing of 3
      generations of An. stephensi with human whole blood using membrane Parafilm "M."
      The maximum feeding rate achieved was 90.9%. Anopheles stephensi, a mosquito
      normally requiring a vertebrate blood meal to produce eggs, has been reared
      successfully for 3 generations on this substitute blood meal.

PMID- 16646323
TI  - Quantification of West Nile virus in the saliva of Culex species collected from
      the southern United States.
AB  - Culex quinquefasciatus, Cx. restuans, Cx. pipiens complex, and Cx. nigripalpus
      were collected as larvae or egg rafts from the southern USA. Adult female
      mosquitoes were intrathoracically inoculated with approximately 1,000 plaque
      forming units of West Nile virus (WNV) and saliva was collected from them 5 days
      later. The amount of infectious WNV in the saliva samples was quantified by
      plaque assay and WNV RNA was detected by reverse transcriptase polymerase chain
      reaction (RT-PCR). More than 90% of the mosquitoes had either infectious virus or
      viral RNA in their saliva. The RT-PCR assay detected a greater percent of samples
      with WNV RNA than the plaque assay detected infectious virus. Pairwise
      comparisons revealed 6 significant differences between the 7 groups surveyed. The
      Cx. nigripalpus secreted lower mean amounts of WNV than 3 other groups, and a
      difference was found between early- and late-season Cx. quinquefasciatus
      collected in Louisiana.

PMID- 16646324
TI  - Evaluation of commercial assays for detecting West Nile virus antigen.
AB  - Two commercially available West Nile virus (WNV) detection assays (RAMP WNV test,
      Response Biomedical Corp., Burnaby, British Columbia, Canada; and VecTest WNV
      antigen assay, Medical Analysis Systems, Inc., Camarillo, CA) were compared for
      sensitivity, specificity, and ability to detect WNV in field-collected mosquito
      pools. Serially diluted stock seed WNV and St. Louis encephalitis virus (SLEV)
      were used to determine sensitivity and specificity. The RAMP WNV test detected
      WNV at concentrations as low as 3.17 log10 plaque-forming units per milliliter
      (PFU/ml), whereas the VecTest assay detected WNV at concentrations as low as 5.17
      log10 PFU/ml. Neither test cross-reacted with SLEV. A WNV-specific reverse
      transcriptase polymerase chain reaction was used to identify positives among
      field-collected mosquito pools. The RAMP WNV test detected 94% of positive pools
      and the VecTest assay detected 65% of the positive field-collected pools. Despite
      these differences, both assays have characteristics that make them useful in WNV
      surveillance programs.

PMID- 16646325
TI  - Vector competence of Peruvian mosquitoes (Diptera: Culicidae) for a subtype IIIC
      virus in the Venezuelan equine encephalomyelitis complex isolated from mosquitoes
      captured in Peru.
AB  - We evaluated mosquitoes collected in the Amazon Basin, near Iquitos, Peru, for
      their susceptibility to a subtype IIIC strain of the Venezuelan equine
      encephalomyelitis complex. This virus had been previously isolated from a pool of
      mixed Culex vomerifer and Cx. gnomatos captured near Iquitos, Peru, in 1997.
      After feeding on hamsters with viremias of about 10(8) plaque-forming units of
      virus per ml, Cx. gnomatos was the most efficient vector. Other species, such as
      Ochlerotatus fulvus and Psorophora cingulata, although highly susceptible to
      infection, were not efficient laboratory vectors of this virus due to a
      significant salivary gland barrier. The Cx. (Culex) species, consisting mostly of
      Cx. (Cux.) coronator, were nearly refractory to subtype IIIC virus and exhibited
      both midgut infection as well as salivary gland barriers. Additional studies on
      biting behavior, mosquito population densities, and vertebrate reservoir hosts of
      subtype IIIC virus are needed to determine the role that these species play in
      the maintenance and spread of this virus in the Amazon Basin region.

PMID- 16646326
TI  - A comparison of two West Nile virus detection assays (TaqMan reverse
      transcriptase polymerase chain reaction and VecTest antigen assay) during three
      consecutive outbreaks in northern Illinois.
AB  - Mosquitoes identified as female Culex (Culex) species, primarily mixtures or
      uniform batches of Culex pipiens and Culex restuans, were collected daily from
      gravid traps by 2 mosquito abatement districts (MADs) in Cook County, Illinois.
      From 2002 through 2004, batches (pools) of mosquitoes were tested by the MADs for
      West Nile virus (WNV) by using VecTest WNV antigen assays and the same samples
      were retested, usually within 1-2 wk, for WNV RNA by the TaqMan reverse
      transcriptase polymerase chain reaction (RT-PCR). There were 952 TaqMan-positive
      pools out of 3,953 pools over the 3 years, and about one half of that number were
      VecTest-positive. The difference between the 2 detection assays varied between
      and within years. The VecTest assays detected about 57% and 69% of the TaqMan RT
      PCR-positive pools from Des Plaines Valley MAD and Northwest MAD in 2002, but
      only about 40% and 46% in 2003, and 36% and 55% in 2004, respectively. Based on a
      subset of the 2004 data, a linear relationship was found between VecTest
      detection of WNV and TaqMan cycle threshold between 18 and 28 cycles. A temporal
      decrease in the difference between the 2 assays was observed in 2003 and 2004,
      which we conjecture is due, at least partially, to a seasonal decline in the
      proportion of recently infected mosquitoes. This trend was not observed in 2002
      because infection rates indicated a high likelihood of more than 1 infected
      mosquito per pool at the peak of transmission. Unlike a previous study, the 95%
      confidence intervals of infection rates based on the 2 detection methods did not
      always overlap. The highest infection rates occurred in 2002 when mean monthly
      temperatures were above average.

PMID- 16646327
TI  - Impact of low aerial application rates of Dibrom 14 on potential vectors.
AB  - Aerial applications designed to assess the impact of low application rates of
      naled (Dibrom 14) on potential vector species were conducted in 2003 with caged
      adult Anopheles quadrimaculatus in open grassland at Cecil Airfield in
      Jacksonville, FL. Offset flight paths of 2,000-6,000 (calculated by the AgDisp
      aerial application model) and 1,000-ft swath widths were conducted with a
      Micronair AU4000 rotary atomizer, which provides a several-fold increase in
      droplets between 7 and 22 microm. Mean volume median diameters of 8.0, 7.8, and
      9.4 microm and 290, 506, and 192 droplets per sq cm were observed in the target
      area with application rates of 0.125, 0.25, and 0.5 fl oz per acre, respectively.
      The observed mean mortality of caged mosquitoes 12 h posttreatment, corrected for
      mortality in untreated controls, was 14%, 80%, and 99% at 0.125, 0.25, and 0.5 fl
      oz per acre, respectively. These results indicate that applications at 0.25 fl oz
      per acre or less should be avoided and rates greater than 0.5 fl oz may be
      required for adequate control in canopied habitats and less-than-optimum
      terrains.

PMID- 16646328
TI  - Laboratory evaluation of the bioinsecticide Spinosad for mosquito control.
AB  - Spinosad, a naturally occurring product of the fermentation of the bacterium
      Saccharopolyspora spinosa, is a highly effective bioinsecticide against a broad
      range of agriculturally important insect pests, and this agent has an excellent
      environmental and mammalian toxicological profile. In this study the efficacy of
      a Spinosad-based product (Laser 4.8% emulsifiable concentrate) was evaluated in
      laboratory bioassays against laboratory-reared mosquito strains of 3 species of
      medical importance: Aedes aegypti, Anopheles stephensi, and Culex pipiens.
      Spinosad was particularly effective against larval Aedes and Culex, with a less
      marked activity against anophelines (24-h median lethal concentration = 0.0096,
      0.0064, and 0.039 mg/liter, respectively), showing a persistence of the
      insecticide action of about 6 wk in laboratory containers. The activity of the
      Spinosad-based product against adult mosquitoes (toxicity by ingestion and a
      possible irritant or repellent effect on gravid females) also was evaluated.
      Results are discussed and compared with those available in the literature.

PMID- 16646329
TI  - Susceptibility of laboratory and field-collected Aedes aegypti and Aedes
      albopictus to Bacillus thuringiensis israelensis H-14.
AB  - Susceptibility levels of a few laboratory-cultured and dengue-endemic area field
      collected strains of Aedes aegypti and Aedes albopictus to Bacillus thuringiensis
      israelensis (Bti) at different storage ages were studied. The susceptibility of
      laboratory-cultured World Health Organization (WHO) Bora Bora reference, Vector
      Control Research Unit (VCRU), and Fumakilla Malaysia Berhad (FMB) strains of Ae.
      aegypti to Bti was examined. The sensitivity to Bti decreased with storage age.
      The median lethal concentration (LC50) for Bti increased by 2-3 times after 2
      years compared to a fresh sample (3-6 months of storage). However, after the 2
      year storage period, Bti still provided very good efficacy against all laboratory
      cultured susceptible strains of Ae. aegypti and Ae. albopictus. The observed 95%
      lethal concentration values were about 20 times lower than the recommended
      concentration (6,000 international toxic units (ITU)/liter). Results obtained
      from the study against the dengue-endemic area field-collected strains of Ae.
      aegypti and Ae. albopictus confirmed the effectiveness of the Bti after storage
      for 2 years (18-24 months). For Ae. aegypti, the Ujung Batu strain was the most
      susceptible to Bti, whereas the Sungai Nibong strain showed the most tolerance.
      Susceptibility of laboratory-cultured strains varied; the Air Itam strain of Ae.
      albopictus was the most susceptible to Bti, whereas the Kampung Serani strain was
      the most tolerant among the field strains. However, the laboratory strain of Ae.
      albopictus was more susceptible than all the field strains.

PMID- 16646330
TI  - Bioefficacy of Olyset nets against mosquitoes in India.
AB  - Olyset nets are highly effective in killing anopheline mosquitoes within 3 min of
      exposure, as evidenced in cone bioassay tests. These nets also showed their
      efficacy on other vector mosquitoes (Aedes aegypti and Cx. quinquefasciatus) at
      higher exposure periods. The efficacy remained at approximately 90% even after 20
      washings at an interval of 24 h against Anopheles culicifacies and Cx.
      quinquefasciatus. Use of the nets inside the house also resulted in drastic
      reduction of daytime resting density of mosquitoes because of high repellency,
      excitorepellency, and killing action of the nets. Pilot studies are indicated to
      evaluate the impact of use of Olyset nets on vector-borne diseases, particularly
      malaria, and its cost-effectiveness in comparison to conventional indoor residual
      spraying.

PMID- 16646331
TI  - Comparative efficacy and persistency of permethrin in Olyset net and
      conventionally treated net against Aedes aegypti and Anopheles stephensi.
AB  - The efficacy of the Olyset net was compared to a net treated conventionally with
      permethrin 10% emulsifiable concentrate at the World Health Organization
      recommended dose. The nets were assessed under laboratory conditions against the
      mosquito vectors Aedes aegypti and Anopheles stephensi. Knockdown efficacy for
      the Olyset net was assessed after the first 10 washings and then after the 15th
      and 20th washings. Data were not collected for the conventionally treated netting
      after 5 washings because the conventional treatment was no longer effective. The
      results of the study indicate permethrin effectively persisted on Olyset net for
      at least 20 washings, confirming the regeneration of pesticide after each wash.

PMID- 16646332
TI  - Effectiveness of mosquito nets treated with a tablet formulation of deltamethrin
      for malaria control in a hyperendemic tribal area of Sundargarh District, Orissa,
      India.
AB  - A village-scale trial on the efficacy of mosquito nets treated with a tablet
      formulation of deltamethrin (K-OTAB) against malaria in comparison to untreated
      nets or no net was conducted in Sundargarh District of Orissa, India, which is
      characterized by perennial transmission with Plasmodium falciparum accounting for
      more than 80% of malaria cases. Three villages with similar topographical and
      epidemiological situations were selected and randomly assigned to 3 arms of the
      study: treated net, untreated net, and no net. Distribution of nets, based on a
      sleeping pattern survey, was carried out to cover 100% of the population in
      treated-net and untreated-net villages. Longitudinal and cross-sectional surveys
      were conducted to measure malaria incidence, prevalence, and splenomegaly.
      Malaria incidence was reduced by 64.3% in the village with treated nets, 45.2% in
      the village with plain nets, and 21.4% in the control village without nets.
      Comparison of malaria incidence data after 1 year of intervention showed
      significant difference between villages with treated net vs. untreated net (P <
      0.05) and treated net vs. no net (P < 0.005). The incidence of clinical attack
      rate due to P. falciparum was significantly lower in the population using treated
      nets than in those using untreated nets and no nets. However, no age-specific
      protective efficacy of treated nets or untreated nets was observed. A significant
      reduction occurred in spleen rate and parasite rate in children aged 2-9 years
      using treated nets or untreated nets. An overall significant reduction was found
      in parasite rate in the total population using treated and untreated nets as
      compared to nonusers.

PMID- 16646333
TI  - Efficacy studies of Aquaprene (emulsifiable concentrate and wettable powder)
      insect growth regulator formulations against third- and fourth-stage larvae of
      Ochlerotatus taeniorhynchus in small-plot field studies.
AB  - Efficacy studies were conducted with Aquaprene emulsifiable concentrate (EC)
      (33.6% active ingredient [AI]) and wettable powder (WP) (40% AI) (S)-methoprene
      insect growth regulator formulations against larval Ochlerotatus taeniorhynchus
      in small field test plots. Aquaprene EC was applied at 7.18 and 9.57 g/acre.
      Approximately one thousand 4th-stage larvae were added to each plot before
      treatment, and 24 h later pupae were collected to determine emergence inhibition.
      At both applications rates, Aquaprene EC was extremely effective (99%) at
      significantly reducing adult emergence in the studies. Two application rates ((S)
      methoprene at 2.4 and 4.8 g/acre) of the Aquaprene WP also were evaluated against
      Oc. taeniorhynchus at 1, 3, 7, and 14 days after treatment. Emergence inhibition
      and statistical analysis showed that significant differences were found between
      the (S)-methoprene rates of 2.4 and 4.8 g/acre at each posttreatment assessment.
      The (S)-methoprene rate of 4.8 g/acre was effective in controlling adult
      emergence for up to 14 days after treatment.

PMID- 16646334
TI  - Mass rearing and egg release of Buenoa scimitra Bare as biocontrol of larval
      Culex quinquefasciatus.
AB  - Backswimmers have been recognized as the most promising predators of mosquito
      larvae. The aim of this investigation was to study mass rearing and egg release
      of Buenoa scimitra for the biological control of Culex quinquefasciatus Say.
      Among the most important results were that production of backswimmer eggs
      occurred for 263 days, and also that eggs were released in artificial containers
      with production of new individuals until the adult stage was obtained. In
      addition, a statistically significant reduction in mosquito larval density was
      observed on some sampling dates.

PMID- 16646335
TI  - Laboratory evaluation of 21 insect repellents as larvicides and as oviposition
      deterrents of Aedes albopictus (Diptera: Culicidae).
AB  - Twenty-one commercial insect repellent products, including 12 botanical, 6 DEET
      based, and 3 synthetic organics, were evaluated as larvicides and as oviposition
      deterrents of Aedes albopictus. Ten of the 12 botanical products at 0.1%
      concentration provided 57-100% mortality of laboratory-reared 4th-stage Ae.
      albopictus larvae at 24 h after treatment. Five of the 6 DEET-based products and
      3 synthetic organic repellents at 0.1% concentration induced 88-100% larval
      mortality at 24 h after treatment. All 12 botanical products proved highly
      effective oviposition deterrents of Ae. albopictus, resulting in 76-100%
      effective repellency at 24 h after exposure. The 6 DEET-based repellents and the
      3 synthetic organic repellents caused 84-100% effective oviposition repellency of
      Ae. albopictus at 24 h after exposure. Several botanical repellents previously
      shown to have minimal protection from mosquito bites proved effective oviposition
      deterrents. Some commercial topical repellents have good potential for
      development and use in management of container-inhabiting mosquitoes because they
      deter oviposition and kill larvae.

PMID- 16646336
TI  - Impact of biting midges on residential property values in Hervey Bay, Queensland,
      Australia.
AB  - Biting midges (Culicoides spp.) are an important environmental health issue in
      Hervey Bay, an area of rapid population growth in Australia. It is also the
      gateway to a World Heritage area (Great Sandy Strait) and a destination for
      tourists. The spread of housing developments into suburbs close to midge breeding
      habitats has led to a problem for the local government responsible for managing
      biting insects in its area. Suburbs with a severe biting midge problem were found
      to have significantly lower residential property values than less affected
      suburbs. The gross reduction in value in due to the midge problem was estimated
      to range from more than AUS dollar 25 million, based on actual sale price, to
      more than AUS dollar 55 million, based on the perceptions of the most severely
      affected residents.

PMID- 16646337
TI  - Mitigating the effects of the green alga Scenedesmus quadricauda on the efficacy
      of Bacillus thuringiensis var. israelensis against larval black flies.
AB  - The green alga Scenedesmus quadricauda has been shown to decrease the efficacy of
      Bacillus thuringiensis var. israelensis (Bti) to black fly larvae in laboratory
      experiments. In this study, 2 approaches to mitigating the effects of S.
      quadricauda were tested, increasing the dose of Bti exposed to the larval black
      flies and increasing the length of the exposure period. Results showed that
      increasing the dose as well as increasing the exposure time were effective
      methods for mitigating the effects of S. quadricauda on Bti efficacy. Assessment
      of larval mortality at different exposure periods to Bti indicate that the
      manifestation of toxicity or acquisition of toxic doses of the Bti formulation
      takes place approximately 2-3 times slower when S. quadricauda is present. These
      results provide information that might be useful in developing a plan of action
      to combat this complex situation in field operations.

PMID- 16646338
TI  - Species composition of mosquitoes of Attapeu Province, Lao People's Democratic
      Republic.
AB  - A list of mosquitoes collected from Lao People's Democratic Republic (Lao PDR)
      from May 2002 to August 2004 is presented. A total of 8,945 mosquitoes belonging
      to 14 genera and 57 species was collected. The genera recorded were Aedes,
      Anopheles, Armigeres, Coquillettidia, Culex, Diceromyia, Downsiomyia,
      Fredwardsius, Mansonia, Neomelaniconion, Ochlerotatus, Paraedes, Stegomyia, and
      Verrallina. Seventeen species are first reports for LAO PDR.

PMID- 16646339
TI  - Anopheles peditaeniatus (Leicester) new to the Iranian mosquito fauna with notes
      on Anopheles hyrcanus group in Iran.
AB  - Anopheles peditaeniatus is reported for the first time in Iran. Species of the
      Hyrcanus Group previously reported in Iran, including An. hyrcanus, An.
      pseudopictus, and An. nigerrimus, are reviewed.

PMID- 16646340
TI  - First record of Aedes albopictus in Croatia.
AB  - The first record of Aedes albopictus in Croatia was made in Zagreb, Croatia, on
      October 28, 2004. A total of 13 larvae were collected in a discarded ceramic
      toilet bowl in a forested area in the southwest suburbs. Because the winter
      temperatures in Zagreb are not favorable for survival, this finding of Ae.
      albopictus may be temporary. Its survival in northern Croatia remains to be
      studied.

PMID- 16646341
TI  - Cold acclimation and overwintering of female Aedes albopictus in Roma.
AB  - Eight years after the introduction and establishment of Aedes albopictus in Roma,
      females of the species extended their trophic activity to the coldest months of
      the year. Winter monitoring carried out from December 2003 to March 2004 in the
      urban area of the capital city of Italy recorded a weekly rate of positive
      ovitraps constantly around 30%, for the entire period of surveillance (14 wk).
      Eggs from ovitraps did not hatch when stimulated in laboratory with a wet and dry
      procedure. The hypothesis that long-lived female Ae. albopictus, belonging to the
      last seasonal generation, could have continued their trophic activity for 3
      months, or that 1 or more cycles of reproduction have occurred in peculiar
      breeding sites, where a favorable microclimate may have allowed the development
      of at least 1 larval generation, are discussed and compared with the existing
      literature.

PMID- 16646342
TI  - Inhibition of adult emergence of Aedes aegypti in simulated domestic water
      storage containers by using a controlled-release formulation of pyriproxyfen.
AB  - Concrete domestic water-storage jars are a common larval habitat of the dengue
      vector Aedes aegypti in countries of Southeast Asia. The efficacy of a novel
      controlled-release formulation of the insect growth regulator pyriproxyfen,
      designed to inhibit adult emergence for 6 months (the approximate duration of the
      main dengue transmission season in many endemic countries) was tested in Cambodia
      against a local strain of Ae. aegypti in 200-liter jars. The resin-based
      formulation contained 4.8% active ingredient (AI). At target dosages of 18, 27,
      and 36 ppb of AI, inhibition of adult emergence remained above 95% for at least 2
      months. After 3 months at 18 ppb AI, the residual efficacy was significantly
      lower than for the higher dosages (P < 0.05). At the higher dosages, inhibition
      of adult emergence was > or = 87% for 6 months. At a dosage of 27 ppb AI, monthly
      removal and replacement of two thirds of the water did not reduce efficacy (P >
      0.05). Potential operational advantages and challenges of using the formulation
      are discussed. Larger-scale efficacy studies are recommended in community
      settings.

PMID- 16646343
TI  - Larvicidal activity of Hibiscus abelmoschus Linn. (Malvaceae) against mosquitoes.
AB  - The larvicidal activity of roots of Hibiscus abelmoschus was evaluated against
      the larvae of mosquitoes in the genera Anopheles and Culex. Mean median lethal
      concentration values of the aqueous extract from the roots of H. abelmoschus
      against the larvae of Anopheles culicifacies, An. stephensi, and Culex
      quinquefasciatus were 52.3, 52.6, and 43.8 ppm, respectively. Efficacy of
      fraction code HAM-4 decreased with an increase in water depth when sprayed at a
      dose calculated by surface area. Fraction code HAM-4 at the rate of 82 ppm showed
      91.1% reduction of larval An. stephensi in a tank, whereas 87.4% reduction of
      larval Cx. quinquefaisciatus occurred in a blocked drain 24 h after application
      of HAM-4 under field conditions.

PMID- 16646344
TI  - Field evaluation of New Mountain Sandalwood Mosquito Sticks and New Mountain
      Sandalwood Botanical Repellent against mosquitoes in North Queensland, Australia.
AB  - The mosquito repellent efficacy of New Mountain Sandalwood Mosquito Sticks
      (containing 0.5% w/w essential oils) and New Mountain Sandalwood Botanical
      Repellent (containing soybean and geranium oils) was assessed. Tests were
      conducted in the field with 4 volunteers in a wooded area near Cairns, North
      Queensland, Australia. Predominant biting species were Verrallina funerea and Ve.
      lineata. A pair of burning Mosquito Sticks immediately upwind of the subject
      (acting as an area repellent) provided a 73.1% mean reduction in mosquito landing
      and probing over the 3-h test period. The Botanical Repellent and a DEET-based
      control were both 100% effective in preventing mosquito probing for 3 h. These
      data are consistent with other studies of area repellents in that such products
      provide significant protection from mosquito bites, albeit inferior to the
      protection provided by topically applied repellents.

PMID- 16646345
TI  - Larvicidal activity of essential oils from Brazilian Croton species against Aedes
      aegypti L.
AB  - Aedes aegypti is the major vector of dengue fever, an endemic disease in Brazil.
      In an effort to find effective and affordable ways of controlling this mosquito,
      the larvicidal activities of essential oils from Croton species widely found in
      northeastern Brazil were analyzed. The essential oils were extracted by steam
      distillation, and their chemical composition was determined by gas liquid
      chromatography coupled with mass spectroscopy. The main components were
      methyleugenol and alpha-copaene for C. nepetaefolius (LC50 of 84 ppm); alpha
      pinene and beta-pinene for C. argyrophyloides (LC50 of 102 ppm); and alpha
      pinene, beta-phelandrene, and trans-caryophyllene for C. sonderianus (LC50 of 104
      ppm). Croton zenhtneri exhibited higher larvicidal activity with LC50 of 28 ppm,
      and the main active constituent was identified as anethole, a phenylpropanoid
      compound.

PMID- 16646346
TI  - William Emery Hazeltine. II: Rebel with a cause.

PMID- 16646347
TI  - Effects of stretch shortening cycle exercise fatigue on stress fracture injury
      risk during landing.
AB  - The purpose of this study was to examine changes in landing performance during
      fatigue that could result in increased stress fracture injury risk. Five
      participants performed nonfatigued and fatigued drop landings (0.60 m), while
      ground reaction force (GRF), electromyographic (EMG) activity, and kinematics
      were recorded. Fatigue was defined as a 5-20% reduction in vertical jumping
      performance. Single-subject analyses revealed that all participants were affected
      (p < or = .05) by fatigue. Post hoc comparisons revealed a group effect (p < or =
      .05) for selected variables. Participants landed with (a) less joint flexion at
      contact and used a greater range of motion, (b) greater GRF peaks and loading
      rates, and (c) less EMG activity. These changes were consistent with greater risk
      of stress fracture.

PMID- 16646348
TI  - Steps counts among middle school students vary with aerobic fitness level.
AB  - The purpose of this study was to examine if steps/day taken by middle school
      students varied based on aerobic fitness classification. Middle school students
      (N = 223; 112 girls, 111 boys) were assigned to three aerobic fitness categories
      (HIGH, MOD, LOW) based on results of the FlTNESSGRAM PACER test. Four weekdays of
      pedometer monitoring determined activity levels (steps/day). Boys accumulated
      significantly more steps/day than girls, 11,589 +/- 3,270 and 10,232 +/- 2,517
      steps/day, respectively; F(1,219) = 16.0, p < .001, eta2 = .055. There were no
      differences in steps/day between grades. HIGH fit participants accumulated
      significantly more steps/day, F(2, 217) = 12.2, p < .101, eta2 = .101, than
      moderately fit and low fit participants (approximately 1,491 and ; 2,867
      steps/day, respectively). Middle school students who participated in sports in
      addition to physical education (PE) accumulated significantly more steps/day
      (approximately 980 steps/day) than those participating in PE only, F(1, 219) =
      10.0, p < .01, eta2 = .044. Although the relationship between physical activity
      and aerobic fitness was moderate (0.35; p < .01), these data demonstrated
      significant differences in accumulated steps/day among youth of varying aerobic
      fitness levels. Whether improved fitness levels were the result of additional
      activity or the cause of it remains to be determined. Regardless, the fittest
      middle school students were also the most active and accumulated a significant
      amount of steps/day through organized extracurricular physical activities.

PMID- 16646349
TI  - Pathways linking perceived athletic competence and parental support at age 9
      years to girls' physical activity at age 11 years.
AB  - Girls' perceived athletic competence and parental support of physical activity
      across the ages of 9 to 11 years were examined as predictors of girls' physical
      activity at age 11 years. Participants were 174 girls and their mothers and
      fathers who completed questionnaires when the girls were ages 9 and 11 years. Two
      alternative temporal pathways linking perceived competence, parental support, and
      physical activity were assessed using path analysis. Results provided evidence
      for the child elicitation pathway; higher perceived competence at the age of 9
      years predicted higher parental support at age 11 years, which, in turn,
      predicted higher physical activity among girls. Findings highlight the importance
      of encouraging parents to make a special effort to support physical activity
      among girls who do not perceive themselves as being athletically competent.

PMID- 16646350
TI  - Teachers' reports of student misbehavior in physical education.
AB  - Classroom management, and, more specifically, the management of student behavior,
      is an essential skill for and central concern of physical education teachers.
      Surprisingly little information is known, however about the specific nature of
      student behaviors that might negatively affect the class environment. The purpose
      of this study was to examine teachers' reports of student behaviors that may
      create management issues in physical education classes. Over 300 teachers
      representing a range of grade levels and school contexts completed a survey
      related to the frequency of potentially negative student behaviors. Many types of
      misbehaviors were reported, but the most common were mild. Teachers' reports
      varied by sex, years of teaching experience, and school context.

PMID- 16646351
TI  - The relationship between heart rate reserve and oxygen uptake reserve in children
      and adolescents.
AB  - The purpose of the present study was to examine the relationship between oxygen
      uptake (VO2) and heart rate (HR) responses during rest and exercise in Chinese
      children and youth and to evaluate the relationships between maximal heart rate
      (%HRmax), heart rate reserve (%HRR), peak oxygen uptake (% VO2peak), and oxygen
      uptake reserve (% VO2R) in Chinese children and youth. Forty-nine Chinese
      children and youth were studied at rest and during a graded maximal exercise test
      on treadmill. Resting, submaximal and peak HR and VO2 were collected. Regression
      analyses were conducted to investigate the associations between the various forms
      of HR and VO2 measures. The equivalency between %HRR and % VO2R for adults was
      examined for children using data obtained in this study. Results indicated that
      all regression lines between HR measures and VO2 measures were significantly
      different from the line of identity (p < .05), except the regression line for
      %HRR versus %VO2 peak in boys. The equivalency between % VO2R and % HRR for
      adults was not demonstrated in children and adolescents in this study. In
      contrast, %HRR was more closely equivalent to % VO2 peak. Because a strong linear
      relationship was found between HR and VO2, HR measures, in terms of either %HRmax
      or %HRR, would still be a practical variable for prescribing appropriate exercise
      intensity for children and adolescents. Unlike results found for adults, a given
      % HRR in children and youth was not equivalent to its corresponding % VO2R.

PMID- 16646352
TI  - Perceived submaximal force production in young adults.
AB  - The purpose of this investigation was to examine the force production patterns
      using perceived stimulus cues from 10% to 90% of maximal force. In Experiment 1,
      54 men (age: 19-34 years) and 53 women (age: 18-37years) performed leg extensions
      on a dynamometer at a speed of 60 degrees/s. Participants produced actual forces
      perceived to be 10-90% of maximal force in 10% increments followed by a maximal
      force. A 2-min rest interval was maintained between each increment. Participants
      rested 5 min and repeated the protocol. Desired forces were calculated as the
      required percentage of the produced maximalforce. In Experiment 2, 40 men (age:
      18-30years)followed the protocol ofExperiment 1, but the submaximal stimuli were
      randomly presented. In Experiment 1, test-retest results indicated consistency
      between the trials for actual and maximal force (r = .90). The correlations
      between actual and desired forces were moderately high (r > .76). Actual forces
      trended above desired forces at 10% of maximal, with median errors ranging 33-40%
      for men and 60-73% for women. From 30% to 90% of maximal forces, actual trended
      below desired forces, with median errors ranging from a low of 1.5% to a high of
      37%. A power function analysis relating the change in actual force with desired
      force stimuli produced exponents of 0.68 (.95 CI = 0.62-0.74) for men and 0.5 7
      (.95 CI = 0.52-0.62)for women. Findings were similar in Experiment 2, indicating
      that individuals tended to overshoot and then undershoot desired force production
      through perceptual force ranges of 10-90% of maximal forces and that force
      production grew more slowly than perceptual stimulus cues. The results of the
      present study, along with findings from past research, indicate that production
      of submaximal force using perceptual cues or stimuli display a great deal of
      specificity. This specificity is related to type of contraction, amount of muscle
      mass involved, and number and types of stimuli.

PMID- 16646353
TI  - Knee extensor and flexor torque development with concentric and eccentric
      isokinetic training.
AB  - This study assessed muscular torque and rate of torque development following
      concentric (CON) or eccentric (ECC) isokinetic training. Thirty-eight women were
      randomly assigned to either CON or ECC training groups. Training consisted of
      knee extension and flexion of the nondominant leg three times per week for 20
      weeks (SD = 1). Eccentric training increased ECC knee extension and flexion peak
      torque more than CON training. The ECC group improved acceleration time and time
      to peak torque with ECC movements versus the CON group. Slow-velocity ECC
      isokinetic training yielded greater ECC and similar CON torque development gains
      versus CON training over the course of 20 weeks in young women.

PMID- 16646354
TI  - Predicting activity energy expenditure using the Actical activity monitor.
AB  - This study developed algorithms for predicting activity energy expenditure (AEE)
      in children (n = 24) and adults (n = 24) from the Actical activity monitor. Each
      participant performed 10 activities (supine resting, three sitting, three house
      cleaning, and three locomotion) while wearing monitors on the ankle, hip, and
      wrist; AEE was computed from oxygen consumption. Regression analysis, used to
      create AEE prediction equations based on Actical output, varied considerably for
      both children (R2 = .45-.75; p < .001) and adults (R2 = .14-.85; p < .008). Most
      of the resulting algorithms accurately predicted accumulated AEE and time within
      light, moderate, and vigorous intensity categories (p > .05). The Actical monitor
      may be useful for predicting AEE and time variables at the ankle, hip, or wrist
      locations.

PMID- 16646355
TI  - Can self-reported preference for exercise intensity predict physiologically
      defined self-selected exercise intensity?
AB  - Exercise prescription guidelines emphasize the importance of individual
      preferences for different intensities, but such preferences have not been studied
      systematically. This study examined the hypothesis that the preference scale of
      the Preference for and Tolerance of the Intensity of Exercise Questionnaire would
      predict self-selected exercise intensity. Twenty-three previously sedentary
      middle-aged women participated in a treadmill test and a 20-min session at a self
      selected intensity. After controlling for age, body mass index, and peak oxygen
      uptake, the preference scale accounted for significant portions of the variance
      in the percentage of oxygen uptake associated with the ventilatory threshold at
      Minute 15 and Minute 20 of the session at self-selected intensity.

PMID- 16646356
TI  - Youth exercise intention and past exercise behavior: examining the moderating
      influences of sex and meeting exercise recommendations.
AB  - The study purposes were to examine: (a) the determinants of exercise intention
      and past exercise behavior (PEB) using the theories of reasoned action and
      planned behavior, and (b) the moderating influences of sex and exercise group
      (meeting or not meeting exercise guidelines). Participants (n = 676 adolescents)
      completed self-reported measures of their exercise attitude, subjective norm,
      perceived behavioral control (PBC), intention, and PEB. We found that attitude,
      subjective norm, and PBC explained 55% of the variance in intention, and
      intention and PBC explained 51% of the variance in PEB. While we found sex and
      exercise group differences across the study measures, we did not find evidence of
      significant moderation. Thus, the theory constructs predicted intention and PEB
      similarly across sex and exercise groups.

PMID- 16646357
TI  - Students' motivational processes and their relationship to teacher ratings in
      school physical education: a self-determination theory approach.
AB  - In the present study, we used a model of motivation grounded in self
      determination theory (Deci & Ryan, 1985, 1991; Ryan & Deci, 2000a, 2000b, 2002)
      to examine the relationship between physical education (PE) students'
      motivational processes and ratings of their effort and persistence as provided by
      their PE teacher. Data were obtained from 394 British secondary school students
      (204 boys, 189 girls, 1 gender not specified; M age = 11.97 years; SD = .89;
      range = 11-14 years) who responded to a multisection inventory (tapping autonomy
      support, autonomy, competence, relatedness, and self-determined motivation). The
      students' respective PE teachers subsequently provided ratings reflecting the
      effort and persistence each student exhibited in their PE classes. The
      hypothesized relationships among the study variables were examined via structural
      equation modeling analysis using latent factors. Results of maximum likelihood
      analysis using the bootstrapping method revealed the proposed model demonstrated
      a good fit to the data, chi-squared (292) = 632.68, p < .001; comparative fit
      index = .95; incremental fit index = .95, standardized root mean square residual
      = .077; root mean square error of approximation (RMSEA) = .054 (90% confidence
      interval of RMSEA = .049 -.060). Specifically, the model showed that students who
      perceived an autonomy supportive environment experienced greater levels of
      autonomy, competence, and relatedness and had higher scores on an index of self
      determination. Student-reported levels of self-determined motivation positively
      predicted teacher ratings of effort and persistence in PE. The findings are
      discussed with regard to enhancing student motivation in PE settings.

PMID- 16646358
TI  - Athletes' evaluations of their head coach's coaching competency.
AB  - This study provided initial validity evidence for multidimensional measures of
      coaching competency derived from the Coaching Competency Scale (CCS). Data were
      collected from intercollegiate men's (n = 8) and women's (n = 13) soccer and
      women's ice hockey teams (n = 11). The total number of athletes was 585. Within
      teams, a multidimensional internal model was retained in which motivation, game
      strategy, technique, and character building comprised the dimensions of coaching
      competency. Some redundancy among the dimensions was observed. Internal
      reliabilities ranged from very good to excellent. Practical recommendations for
      the CCS are given in the Discussion section.

PMID- 16646359
TI  - Ratings of perceived exertion of ACSM exercise guidelines in individuals varying
      in aerobic fitness.
AB  - The physiological responses of high (HF) and low fit (LF) individuals at given
      perceived exercise intensities were compared to ranges provided by the American
      College of Sports Medicine (ACSM). Participants were 7 LFand 8 HF men between the
      ages of 22 and 26 years. All participants performed a maximum oxygen uptake and
      lactate threshold test and two 15-min experimental runs in which they exercised
      at a constant perceived exercise intensity (RPE 13 and 17). The LF group
      exhibited significantly greater maximum oxygen uptake reserve ( % VO2R, p < .05)
      and velocity of lactate threshold (p < .01) values than HF at RPE 13 and 17. Both
      groups had significantly greater % VO2R and maximum heart rate values at RPE 13
      in comparison with the ACSM ranges, using the highest value for the given range
      (p < or = .001).

PMID- 16646360
TI  - Revisiting the development of time sharing using a dual motor task performance.

PMID- 16646361
TI  - Age and function differences in shared task performance: walking and talking.

PMID- 16646362
TI  - Using momentary time sampling to estimate minutes of physical activity in
      physical education: validation of scores for the system for observing fitness
      instruction time.

PMID- 16646363
TI  - [Modifying our "obesogenic" environment: which hints?].
AB  - Overweight is nowadays a major problem of public health in Switzerland. Swiss
      people eat too much, too much fat, sugar and salt! Most efficient public health
      strategies are global and also apply to environmental modifications, an important
      determinant to change individual behaviours. Today, our environment is
      "obesogenic": unlimited access to food, food industry marketing, lifestyle
      changes. As global programmes for smoking cessation and cardiovascular diseases
      prevention, it is urgent to propose interventions taking into account all
      environmental factors which could support individuals in their efforts of
      changes.

PMID- 16646364
TI  - [The keys to lose weight].
AB  - Losing weight is not only a pound's problem! It is a long and strenuous process.
      Rapidly, the care giver or the patient may be demotivated by lack of success. It
      is important to systematize the follow-up and sustain motivation. Firstly, this
      article points out the difficulties met during the follow-up: these difficulties
      linked both to the patient and the health care provider could be at the origin of
      resistance to weight loss. Secondly, we propose seven criteria to be evaluated in
      order to follow the patients towards the process of weight loss.

PMID- 16646365
TI  - [Are PUFAs n-3 really important in diet?].
AB  - If cardiovascular secondary prevention as well as COPD benefit from PUFAs
      supplementation, mainly in our societies where n-3 lack is close to n-6:n-3
      misbalance, the usefulness of these supplements in many diseases (inflammatory or
      psychiatric for instance), is not yet established despite numerous randomised
      controlled studies and meta-analysis. The only counter indication to their
      prescription now is the presence of an implantable defibrillator. Their effect on
      prostate cancer remains doubtful. PUFAs n-3 marine sources should be free of
      pollution.

PMID- 16646366
TI  - [Nutritional follow-up after gastric bypass].
AB  - Roux-en-Y gastric bypass has become one of the main bariatric procedures. This
      surgical operation shows excellent results in weight evolution and quality of
      life and allows a decrease of mortality. However, it leads, relatively often, to
      nutritional deficiencies which need an effective post-operative follow-up. This
      follow-up includes not only medical and dietetic encounters but also regular
      blood analyses made every 3 months during the first post-operative year, every 6
      months the second year, then each year. The most frequent deficiencies are those
      in vitamin B12, iron and folic acid. The secondary hyperparathyroidism
      characterized by an increase of PTH associated to a low vitamin D and a normal
      calcium, is quite frequent.

PMID- 16646367
TI  - [Knowledges and beliefs related to nutrition of obese and overweight patients
      subjects: a study in Southern Italy].
AB  - 303 obese and overweight south Italian patients (240 women and 63 men),
      volunteers to participate in a patient education programme delivered by the
      university hospital of Foggia, have fullfiled a 50 items true/false test
      exploring the knowledges and the beliefs on obesity, nutrition, physical
      activities. The majority of the subjects has both low socio economical status and
      education level. Women have better performed than men (p<0.005) and obese
      patients, better than overweight subjects (p<0.005). The more frequent mistakes
      have concerned items on nutrition, meanwhile a better performance has been
      observed with the items on beliefs.

PMID- 16646368
TI  - [Patient's resistance: to what? to whom?].
AB  - An approach for "resisting patients" to treatments and weight loss programme is
      proposed. Patient's resistance is a sign of vitality, a source of information for
      the health care provider and an invitation to question the nature of therapeutic
      relationship. Resistance can constitute a "block road" which the health care
      provider may not be able to avoid unless initiating a process of changes based on
      reciprocal responsibilities and implications. Towards a patient resisting to
      change, it is appropriate to understand how he resists, to what and, perhaps to
      whom. Practical proposals to "do and to be with a resisting patient" can be
      applied by health care providers taking care of patients suffering from binge
      eating disorders and obesity.

PMID- 16646369
TI  - [The obese patient's therapeutic course].
AB  - Obesity as a chronic disease needs a global approach taking into account, not
      only usual anthropometrical measurements allowing to define severity and the type
      of obesity (BMI and waist circumference) but also others parameters to evaluate
      the patient's morbid conscience and his level of motivation towards a potential
      treatment. Obese patient's possible therapeutic course is developed in this
      article according to three important parameters: eating disorders, motivation and
      capacity of introspection. The aim is to give tools to the generalist to select
      patients needing a multidisciplinary follow up in a specialized centre and those
      who can be treated in the office.

PMID- 16646371
TI  - [The limitation of informatics is its memory].

PMID- 16646370
TI  - [Generic drug prescribing: pilot study on the impact of the new drug pricing
      system on costs and potential savings].
AB  - The impact of a systematic generic substitution and of the new drug pricing
      system (implemented in 2002 for cost saving reasons) on prescription cost was
      computed on the basis of prescriptions delivered in January 1999 for patients
      leaving our university hospital. A total of 3,099 prescriptions, representing
      5,514 drugs, were delivered in one month, of which 335 (6%) were excluded (drug
      not available in 2002 or magistral preparations). Forced generic prescription
      would have saved 3,8% of global costs, while the new drug pricing system would
      have increased costs between 1,1% and 8,0%. In this specific setting, savings
      linked with forced generic drug prescription was weak (4 to 5%), and the expected
      savings of the new drug pricing system were not observed.

PMID- 16646372
TI  - [Acute lymphoblastic leukemia in children and adolescents].

PMID- 16646373
TI  - [Mr. P.'s jaundice].

PMID- 16646374
TI  - [Can one reasonably prescribe an antidepressant to a child? (2)].

PMID- 16646375
TI  - [When Doctors Without Borders writes to Miles White, chairman of Abbott
      Laboratories].

PMID- 16646376
TI  - [The force of the disputed habit].

PMID- 16646377
TI  - [Hair].

PMID- 16646378
TI  - Protecting China's rivers.

PMID- 16646379
TI  - European Union (EU) risk assessment for zinc and zinc compounds.

PMID- 16646380
TI  - Ecological impact in ditch mesocosms of simulated spray drift from a crop
      protection program for potatoes.
AB  - Outdoor aquatic ditch mesocosms were treated with a range of pesticides to
      simulate various spray drift rates resulting from a typical crop protection
      program used in the cultivation of potatoes in The Netherlands. The main
      experimental aims of the present study were to provide information on the fate
      and ecological effects of drift of the pesticides into surface water and to
      evaluate the effectiveness of drift-reduction measures in mitigating risks. The
      pesticides selected and the dosage, frequency, and timing of application were
      based on normal agricultural practices in the potato crop. Applications of
      prosulfocarb, metribuzin (both herbicides), lambda-cyhalothrin (insecticide),
      chlorothalonil, and fluazinam (both fungicides) were made in the sequence typical
      of the spray calendar for potatoes. A total of 15 treatments with the various
      compounds were made by spray application to the water surface at 0.2%, 1%, and 5%
      of the recommended label rates. Chemical fate and effects on ecosystem function
      and structure (phytoplankton, zooplankton, chlorophyll-a, macroinvertebrates,
      macrophytes, breakdown of plant litter) were investigated. To interpret the
      observed effects, treatment concentrations were also expressed in toxic units
      (TU), which describe the relative toxicity of the compounds with standard
      toxicity test organisms (Daphnia and algae). After treatment, each compound
      disappeared from the water phase within 2 d, with the exception of prosulfocarb,
      for which 50% dissipation time (DT50) values ranged between 6 and 7 d. At the 5%
      treatment level, an exposure peak of 0.9 TUalgae was observed, which resulted in
      short-term responses of pH, oxygen, and phytoplankton. At the 5% treatment level,
      exposure concentrations also exceeded 0.1 TUDaphnia, and this resulted in long
      term effects on zooplankton and macroinvertebrates, some of which did not fully
      recover by the end of the present study. At the 1% treatment level, only slight
      transient effects were observed on a limited number of zooplankton and macro
      invertebrate species and on pH. At the 0.2% level, no consistent treatment
      related effects were observed. Most of the observed effects were consistent with
      the results from higher-tier and mesocosm studies with the individual compounds.
      Multi and repeated stress played a small role within the applied pesticide
      package, because of rapid dissipation of most substances and the absence of many
      simultaneous applications. This suggests that risk assessments based on the
      individual compounds would in this case have been sufficiently protective for
      their uses in a crop protection program.

PMID- 16646381
TI  - Background levels of metals in St. Lawrence River sediments: implications for
      sediment quality criteria and environmental management.
AB  - Preindustrial sediments dredged from the St. Lawrence Seaway are often considered
      potentially toxic relative to interim sediment quality criteria. The aim of the
      present study was to better document the background levels of target metals that
      were once used to define the minimal threshold of these criteria. Three
      extractions were performed on sediment samples to evaluate the distribution and
      potential bioavailability of trace metals. The results showed that the background
      levels established for the criteria are representative of contaminant
      concentrations observed in preindustrial sediments but not of the postglacial
      marine clays underlying these sediments. Chromium, nickel, and copper
      concentrations in postglacial marine clays, when solubilized by strong acids,
      exceeded the minimal effect threshold, whereas chromium and nickel frequently
      exceeded the toxic effect threshold and therefore are problematic in terms of
      applying sediment quality assessment criteria. The results suggest that these
      trace metals are mostly associated with inert silicates in postglacial marine
      clays and are unlikely to be bioavailable to aquatic organisms. Postglacial
      marine clays should be better considered differently than are sediments in regard
      to the sediment quality criteria implementation. Accordingly, the use of tools to
      identify the postglacial material may become necessary if a particular management
      disposition should be established for this sedimentary material. Total
      recoverable aluminum concentrations in sediments, in conjunction with other
      physical characteristics, was shown to be an interesting tool to identify this
      specific material. The normalization of metals concentrations with total
      recoverable aluminum concentrations would take account of natural mineralogical
      and textural variability of freshwater sediments in the quality assessment
      process.

PMID- 16646382
TI  - Residential energy use and potential conservation through reduced laundering
      temperatures in the United States and Canada.
AB  - A residential energy-use model was developed to estimate energy budgets for
      household laundering practices in the United States and Canada. The thermal
      energy for heating water and mechanical energy for agitating clothes in
      conventional washing machines were calculated for representative households in
      the United States and Canada. Comparisons in energy consumption among hot-, warm
      , and cold-water wash and rinse cycles, horizontal- and vertical-axis washing
      machines, and gas and electric water heaters, were calculated on a per-wash-load
      basis. Demographic data for current laundering practices in the United States and
      Canada were then incorporated to estimate household and national energy
      consumption on an annual basis for each country. On average, the thermal energy
      required to heat water using either gas or electric energy constitutes 80% to 85%
      of the total energy consumed per wash in conventional, vertical-axis (top
      loading) washing machines. The balance of energy used is mechanical energy.
      Consequently, the potential energy savings per load in converting from hot-and
      warm- to cold-wash temperatures can be significant. Annual potential energy and
      cost savings and reductions in carbon dioxide emissions are also estimated for
      each country, assuming full conversion to cold-wash water temperatures. This
      study provides useful information to consumers for conserving energy in the home,
      as well as to, manufacturers in the design of more energy-efficient laundry
      formulations and appliances.

PMID- 16646383
TI  - Ecology in a cost-benefit society: the issues.
AB  - Is there a role for ecology in a cost-benefit society? As a theme held at
      Roskilde University in June 2004, this paper summarizes divergent approaches to
      public policy decision making. Whether based on strict cost-benefit analysis or
      wide-ranging discussion, we make the point that decisions need to be informed by
      an understanding of the causes behind environmental problems and their
      consequences, through impaired ecosystem services, on the economy. Taking this
      forward will require forums that bring ecologists, economists, and regulators
      into active and constructive dialogue.

PMID- 16646384
TI  - Cost-benefit analysis and the water framework directive in Scotland.
AB  - The Water Framework Directive seeks to achieve the enhancement of aquatic
      ecosystem quality for all waters across Europe. However, it recognizes the need
      to accommodate social and economic considerations, so Heavily Modified Water
      Bodies may be designated where achievement of the Directive's objectives may
      result in disproportionate costs. This necessitates the use of cost and benefit
      data, which may be hard to acquire. Benefits and costs of implementing the
      Directive also can be tested at the national level. This paper considers the
      evaluation of costs and benefits at 2 scales in Scotland: microlevel analysis,
      for case studies on the rivers Tummel and Dee and the Forth Estuary, and
      macrolevel analysis. In the microlevel analysis, costs of hydroelectric power
      generation are compared with the marginal benefits of increased fisheries
      revenues and are argued to be disproportionate. In the estuary environment, the
      benefits of returning an area to ecologically productive salt marsh and mudflats
      are compared with the costs of lost agricultural revenue. In the macrolevel
      analysis, we compare the costs to impacted industries with the estimated national
      benefits from implementing the Directive. We find that for Scotland as a whole,
      implementation is predicted to result in positive net social benefits.

PMID- 16646385
TI  - Thinking broadly about costs and benefits in ecological management.
AB  - Decisions regarding both human and natural systems often involve either explicit
      or implicit consideration of relative costs and benefits. These costs and
      benefits, however, go well beyond those captured in conventional economic cost
      benefit analysis. It is not so much the mere consideration of costs and benefits
      that hampers cost-benefit analysis but, rather, the narrowness and incompleteness
      of the subset of costs and benefits that are usually considered. To use cost
      benefit analysis for social decision making, one needs to think very broadly
      about which categories of costs and benefits need to be addressed (including
      effects on built, human, social, and natural capital as well as sustainable well
      being) and deal with the inherent uncertainty and imprecision attached to many of
      the more important categories. One needs to consider the full range of possible
      values and valuation methods, to shift the burden of proof to the parties that
      stand to gain from the decision, to deal with the distributional consequences of
      decisions, and to be clear about the social goals being served by the decision.
      Failure to think broadly enough about costs and benefits leads to decisions that
      serve only narrow special interests, not the sustainable well-being of society as
      a whole.

PMID- 16646386
TI  - Valuation of biodiversity effects from reduced pesticide use.
AB  - This study deals with the effects on biodiversity of pesticide-free buffer zones
      along field margins. Using choice modeling, the majority of respondents to a
      survey on pesticide use in the environment are willing to accept an increase in
      the price of bread if the survival of partridge chicks and the number of wild
      plants increase. The study identifies the need for further empirical work with
      respect to methodological validation, price estimation, and the use of survey
      results in policy analysis. In particular, the environmental effects of pesticide
      use are complex and, therefore, present difficult challenges when presenting
      information to lay people. Forty-one percent of respondents changed their
      responses regarding willingness to pay more for bread when references to
      pesticide use were introduced in the questionnaire. This indicates that scenarios
      depicting changes in pesticide use can be difficult to present to lay people in
      an economically rational and well-defined context. Thus, in the study of
      valuation related to changes in pesticide use, much attention should be devoted
      to the design and definition of the context. Furthermore, the effects of
      providing different background information, e.g., with or without the mention of
      pesticides, should be tested.

PMID- 16646387
TI  - Democracy and sustainable development--what is the alternative to cost-benefit
      analysis?
AB  - Cost-benefit analysis (CBA) is part of neoclassical economics, a specific
      paradigm, or theoretical perspective. In searching for alternatives to CBA,
      competing theoretical frameworks in economics appear to be a natural starting
      point. Positional analysis (PA) as an alternative to CBA is built on
      institutional theory and a different set of assumptions about human beings,
      organizations, markets, etc. Sustainable development (SD) is a multidimensional
      concept that includes social and ecological dimensions in addition to monetary
      aspects. If the political commitment to SD in the European Union and elsewhere is
      taken seriously, then approaches to decision making should be chosen that 1st
      open the door for multidimensional analysis rather than close it. Sustainable
      development suggests a direction for development in a broad sense but is still
      open to different interpretations. Each such interpretation is political in kind,
      and a 2nd criterion for judging different approaches is whether they are
      ideologically open rather than closed. Although methods for decision making have
      traditionally been connected with mathematical objective functions and
      optimization, the purpose of PA is to illuminate a decision situation in a many
      sided way with respect to possibly relevant ideological orientations,
      alternatives, and consequences. Decisions are understood in terms of matching the
      ideological orientation of each decision maker with the expected effects profile
      of each alternative considered. Appropriateness and pattern recognition are other
      concepts in understanding this process.

PMID- 16646388
TI  - Costs and benefits of communicating product safety information to the public via
      the Internet.
AB  - Procter & Gamble (P&G) developed Science-in-the-Box (SIB;
      www.scienceinthebox.com) after discussions with their stakeholders as to how the
      consumer products company could better communicate key environmental performance
      and safety information to the public. A series of workshops enabled P&G to
      understand that consumers and other key business decision makers wanted
      meaningful information about the science behind P&G products. In addition, it was
      clear that making such information available would produce business benefits by
      encouraging long-term relationships with decision makers ranging from consumers
      and retailers to policy makers and nongovernmental organizations. These benefits
      were not necessarily quantifiable in the short term, but they still had to be
      balanced by the costs in terms of resource commitment and potential intellectual
      property issues. Since its inception in September 2002, SIB has successfully
      reached key target audiences and built improved credibility and confidence in P&G
      products and approaches. The website is now available in English, French,
      Spanish, German, and Italian and is used by consumers, journalists, teachers,
      scientists, and policy makers. Several user surveys carried out during the
      initial developmental period, together with unsolicited e-mail feedback, have
      demonstrated that SIB has successfully created a platform for continuous dialogue
      with consumers and other interested parties.

PMID- 16646389
TI  - Minimizing environmental impacts of a major construction: the Oresund link.
AB  - The Oresund Link is a 4-lane motorway with a 2-line rail link between Copenhagen,
      Denmark, and Malmo, Sweden, built across the Oresund Sound between the 2
      countries. The environmental concerns associated with construction of the Link
      were that that it might affect the water and salt flow through the Sound and into
      and out of the Baltic Sea, lead to destruction of the cod fishery, and affect
      other biological systems. An International Expert Panel was formed to design
      mitigation strategies to avoid negative environmental impacts. The Panel designed
      stringent environmental controls for the construction, of which the most
      significant was to limit sediment discharges to 5% of the dredged material. This
      was one-fifth of the discharge limit construction companies usually accept as
      normal for such a large-scale project. An environmental monitoring program was
      instituted to monitor compliance with the environmental control measures. As a
      result of the imposition of tough environmental requirements, the Link was built
      with little environmental impact and 3 y after it was completed, environmental
      conditions have returned to normal.

PMID- 16646390
TI  - Access to health care among Hispanic or Latino women: United States, 2000-2002.
AB  - OBJECTIVE: This report presents national estimates on access to health care for
      the following five subgroups of Hispanic or Latino women aged 18 years and over
      in the United States: Mexican, Puerto Rican, Cuban, Central or South American,
      and other Hispanic. For comparison, estimates are also presented for non-Hispanic
      white women and non-Hispanic black women. METHODS: Data for persons of all ages
      in the U.S. civilian noninstitutionalized population are collected each year in
      the National Health Interview Survey (NHIS), which is conducted by the Centers
      for Disease Control and Prevention's National Center for Health Statistics. Each
      year, data are collected for approximately 100,000 persons in 40,000 households.
      In the 2000-2002 surveys combined, data were collected for 54,763 women aged 18
      years and over (9,082 Hispanic or Latino women), with an overall response rate of
      73.4%. Estimates in this report are presented as annual estimates, averaged over
      the 3 survey years. Estimates were age adjusted to the 2000 U.S. standard
      population to permit comparison among the various race and ethnic subgroups.
      RESULTS: Among the 33.4 million Hispanic or Latino women in the United States,
      31% lacked health insurance coverage at the time of interview, 20% had no usual
      place to go for medical care during the past year, and 22% experienced unmet
      health care needs during the past year due to cost. Of the five subgroups of
      Hispanic or Latino women, Mexican women (35%) and Central or South American women
      (36%) were more likely than Puerto Rican women (14%) and Cuban women (23%) to
      lack health insurance coverage. Mexican women (78%) and Central or South American
      women (78%) were less likely to have a usual place to go for health care compared
      with Puerto Rican women (90%), Cuban women (82%), and other Hispanic women (90%).
      The percentage of Hispanic or Latino women who had an unmet medical need due to
      cost was highest among Mexican women (24%) and lowest among Cuban women (14%).
      Lack of access to health care was most prevalent among Hispanic or Latino women
      who had poor or near poor poverty status, had less than a high school diploma, or
      were foreign born. CONCLUSION: Access to health care varied among subgroups of
      Hispanic or Latino women. Understanding these subgroup differences may help
      community-based programs improve access to care among Hispanic or Latino women.

PMID- 16646391
TI  - Prevention of mucogingival defects around dental implants: a review.

PMID- 16646392
TI  - How to reduce practice stress.

PMID- 16646393
TI  - Replacement of a fractured upper central incisor with an implant-supported crown:
      a step-by-step approach to achieve acceptable esthetics.
AB  - Implant-supported restorations in the upper anterior segment need to meet
      biological, functional, and esthetic requirements to be successful. Bone
      availability and soft-tissue characteristics in the area of implant placement are
      crucial for achieving maximum success. This article describes the steps involved
      in replacing a fractured upper central incisor with an implant-supported crown.
      Using surgical techniques involving extraction socket preservation/augmentation
      and connective tissue grafting, ideal positioning of the implant was possible and
      gingival contours were idealized. With this multiple step treatment, the final
      restoration met biological and functional requirements and its esthetic results
      were maximized.

PMID- 16646394
TI  - Diagnosing and treating the patient with restricted mandibular opening: a new
      approach.
AB  - Patients with a restricted mandibular opening and related pain require a
      systematic process for differential diagnosis and treatment planning. This
      article considers the differential diagnostic process, treatment planning, and
      treatment delivery for a patient seeking a second opinion before surgery for a
      closed lock. A closed lock occurs when the disc in the joint has been pulled off
      the head of the condyle and forward, blocking the condyle from translating
      forward.

PMID- 16646395
TI  - Immediate transition to an implant-supported dentition.
AB  - Immediate implant placement and loading is becoming increasingly acceptable.
      However, to be successful, very careful case selection is required, and even if
      this is achieved, the clinical situation that develops as soon as the natural
      teeth are removed may prove much less adequate for implant stability,
      positioning, and survival than anticipated. It makes sense to "over engineer" a
      case and to place more implants rather than fewer to ensure adequate support
      during the critical early phase of therapy, particularly when the implants are
      loaded at the time of placement. It also should be appreciated that immediate
      transition induces gross changes that can make it difficult to predict the final
      esthetic outcome.

PMID- 16646396
TI  - A clinical report on the 18-month cumulative survival rates of implants and
      implant prostheses with an internal connection implant system.
AB  - Titanium implants have been successful in both dentulous and edentulous patients.
      The original Branemark titanium implants were introduced with external hex
      connections between implants and abutments. Successes and failures/complications
      with both the biology and mechanics of this connection system have been reported.
      In an attempt to improve the predictability and success of implant/abutment
      connections, internal connections between implants and abutments were developed
      significantly differently from external implant/abutment connections in terms of
      size, surface area, and geometry. Forty-five consecutive partially edentulous
      patients were treated with 83 implants (Osseotite Certaina). The implants were
      allowed to heal for at least 8 weeks without occlusal loading. All were restored
      with single, nonsplinted restorations. The implants were loaded with fully
      functional occlusions for at least 1 year. Recall appointments were scheduled at
      1, 6, 12, 18, 24, and 36 months after implant placement. Eighty-two of the 83
      implants were clinically stable and considered to be osseointegrated 18 months
      after occlusal loading for a cumulative survival rate (CSR) (implants) of 100%.
      All of the abutment screws and restorations were non-mobile 18 months after
      occlusal loading for a CSR (prostheses) of 100%. This internal implant/abutment
      connection was clinically successful and should benefit restorative dentists
      involved in implant dentistry by decreasing the number of maintenance visits and
      problems associated with dental implant treatment.

PMID- 16646397
TI  - [Morphologic quantitative analysis of nucleus in laryngeal squamous cell
      carcinoma with Automatic Image Cytometry].
AB  - OBJECTIVE: Analyze morphological character of nucleus in laryngeal squamous cell
      carcinoma with Automatic Image Cytometry, discuss the relation between
      morphological parameters and tumor clinic. METHOD: We discussed morphological
      character of nucleus from 83 cytology specimens which included 21 laryngeal
      squamous cell carcinomas and 20 benign diseases with Automatic Image Cytometry.
      RESULT: Nucleus from laryngeal squamous cell carcinomas had bigger nuclear area
      nuclear radius, nuclear perimeter and more DNA content per nuclear area than from
      laryngeal benign diseases, furthermore, these parameters showed distinct
      difference in different anatomic positions and different pathologic types. We
      concluded that nuclear areas of nucleus in S phase from laryngeal squamous cell
      carcinomas are more than 77 microm, Second Order Regression Equation(Y =aX2+bX+c)
      described scattered diagrams between mean nuclear radius and nuclear area of
      laryngeal cytology specimens with different larynx pathology and different cell
      phase in cell cycle. The more the value of coefficient "c"(c>1.82) and the less
      the value of coefficient "b" (b< 0.045), the more the probability of malignant
      tumor diagnosis. CONCLUSION: Morphologic quantitative analysis parameters, such
      as nuclear area, mean nuclear radius, nuclear perimeter and DNA content per
      nuclear area, are suitable for diagnosing laryngeal squamous cell carcinomas.
      They could offer valuable morphologic quantitative criterion in assisting
      cytology diagnose and evaluating tumor clinical characters when these parameters
      associated with nuclear area of nucleus in S-phase and the coefficients of Second
      Order Regression Equation.

PMID- 16646398
TI  - [The application of multi-slice computed tomograph in diagnosis and operation of
      hypopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the clinical application of multi slice CT(MSCT) in
      hypopharyngeal carcinoma and serve otolaryngologist to institute proper
      operation. METHOD: Forty-five patients with hypopharyngeal carcinoma scanned by
      MSCT were studied and confirmed by operation and pathologic examination. The
      operation material were retrospectively analyzed. All the cases were used for the
      enhancement scanning, whose scope was from hard palate to cervical segments of
      esophagus. RESULT: Of 45 cases, 34 cases derived from piriform fossa, 7 cases
      were from the postcricoid region and 4 cases were in the posterior wall of
      hypopharynx. The tumor showed isodense or mixed density and slightly enhancement,
      piriform fossa became narrow or disappeared, retropharyngeal soft tissue
      thickened, laryngeal cartilage and esophageal ostium were invaded and lymph nodes
      of neck became metastasis. The tumor pushed the annular and arytenoids cartilage
      displacement anteriorly; the thyroid arytenoidal gap and cricothyroid joint were
      widened. The operation plan that was made according as MSCT was almost agreed
      with actual operation. The consistent rate is 91.1% (41/45). CONCLUSION: MSCT
      examination can accurately diagnose and exhibit the extension of the tumors and
      detect metastasis to lymph nodes, and provide reliable basis for surgery therapy.

PMID- 16646399
TI  - [The application of metal stent in the treatment of adult non neoplastic tracheal
      stenosis].
AB  - OBJECTIVE: To assess the feasibility and the curative effect of the metal stent
      inserted in non neoplastic tracheal stenosis. METHOD: In this study, 7 patients
      were treated with endotracheal metal ultraflex stent for non neoplastic tracheal
      stenosis, who had a contraindication or refuse to the surgery operation. There
      are six cases, their length of tracheal stenosis more than 4 cm. The other one,
      tracheal stenosis located at the tracheal fistula after total laryngectomy. Non
      silica gel membrane metal stent were used in four cases, silica gel membrane
      metal stent were used in three cases. RESULT: These stents were well tolerated
      and produced immediate symptomatic and functional improvement. Granulation tissue
      without obstruction of the airway was observed in 6 patients; only one patient
      had a local recurrence that needed a re-tracheotomy. One patient had to pull out
      the stent after 10 months of operation. The reason is local discomfort.
      CONCLUSION: Metal stent has a good curative effect in the treatment of non
      neoplastic tracheal stenosis, especially for the nonresectable patient, and it is
      easy to operate. However, the results are not sufficient to assess the efficacy
      and tolerance of the device in the medium and the long term.

PMID- 16646400
TI  - [Research on the change of PSG parameters of OSAHS patients before and after UPPP
      operation].
AB  - OBJECTIVE: To study the change of polysomnography (PSG) parameters of obstructive
      sleep apnea hypopnea syndrome (OSAHS) patients before and after
      uvulopalatopharyngoplasty (UPPP) operation. METHOD: Having PSG detection for this
      20 OSAHS patients both before and after UPPP operation. RESULT: (1) After UPPP
      operation, AHI (P<0.01), average SaO2 (P<0.01), Min SaO2 (P<0.01), and apnea time
      contrast (P<0.05)have improvements; (2) After UPPP operation, the change of sleep
      stage mainly S2 stage replaced S stage. (3) In observation index of PSG, both the
      relationship between AHI and oxygen saturation and the relationship between AHI
      and apnea time have correlation, but correlation of the former has more
      significant difference in statistics. The change of AHI and MinSaO2 after UPPP
      operation has correlation also. The secant plane of oropharynx can be regarded as
      the predictive index for OSAHS severity and guideline for UPPP operation, but the
      change of oropharyngeal secant plane after operation can not be used as the
      predictive index for therapeutic effectiveness. CONCLUSION: So we treat oxygen
      saturation as a more sensitive marker than apnea time in predicting severity
      degree of OSAHS. After UPPP operation, the change of sleep stage mainly S2
      replaced S1 stage.

PMID- 16646401
TI  - [To study the expression of dendritic cell phenotypic antigen in cervical lymph
      nodes in hypopharyngeal carcinoma].
AB  - OBJECTIVE: Dendritic cells express many cell phenotypic antigens, they have
      different special function in the process of antigen present. The purpose of this
      study was to determine some DC phenotypic antigen in cervical lymphnodes in
      hypopharyngeal carcinoma and evaluate the relationship between the DC phenotypic
      antigen expression in hypopharyngeal carcinoma metastasis and prognosis. METHOD:
      Envision HIS method was performed to detect the cell surface markers S-100, CD1a
      and CD83. 144 cervical lymph nodes obtained from 37 cases of hypopharyngeal
      carcinoma were evaluated. Furthermore, the relationship between CD45RO+ T
      lymphocytes and dendritic cells was observed. RESULT: The number of S-100+ DCs,
      CD1a+ DCs and CD83+ DCs in the cases of lymphnode metastasis were fewer than
      those in non-lymphnode metastasis. There is a significant metastasis difference
      in statistics between lymphnode metastasis groupe and non-lymphnode metastasis
      group. The number of CD83+ DCs located at cancerous nest area were fewer than
      those at peritumor area in lymphnode metastasis groupe. There is a significant
      difference in statistics between them. The number of CD83+ DCs in the cases of
      survival group were more than those in obituary group. CD45RO+ T cells mainly
      distribute around CD83+ DCs. CONCLUSION: The expression of dendritic cells
      phenotypic antigens were significant difference in different areas in lymphnodes,
      may play difference role in tumor immunity against hypopharyngeal carcinoma.
      Dendritic cells phenotypic antigens were the important markers to predict the
      prognosis of the patients with hypopharyngeal carcinoma.

PMID- 16646402
TI  - [Correlation between expression of the MTA1 gene and carcinomas of larynx].
AB  - OBJECTIVE: To study the relation between Mta1 gene (metastasis associated gene,
      meta gene) and lymph node metastasis of laryngeal carcinomas. METHOD: Reverse
      transcription polymerase chain reaction(RT-PCR) technique was used to detect the
      expression of Mta1 mRNA in 30 carcinoma of larynx tissue cases, 12 lymph nodes
      and 10 normal larynx tissue cases. RESULT: The frequency of MTA1 overexpression
      was 100% (8/8) in primary carcinomas of larynx with metastasis but only 22.7%
      (5/22) in toes without metastasis (P<0.01). Expression of MTA1 was 87.5%(7/8) in
      lymph nodes with metastasis but only 0(0/4) in toes without metastasis(P<0.05).
      The frequency of Mta1 overexpression was 43.3% (13/30) in primary carcinomas of
      larynx. CONCLUSION: Our data suggest that the overexpression of the MTA1 gene
      correlates with lymph node metastasis of carcinomas of larynx. Mta1 gene will
      probably become a valuable gene for judging metastasis of laryngeal carcinoma.

PMID- 16646403
TI  - [The relationship between ECM1 and the angiogenesis and metastasis of laryngeal
      carcinoma].
AB  - OBJECTIVE: To investigate the expressions of extracellular matrix protein-1
      (ECM1) in laryngeal carcinoma and their relationships with the growth, metastasis
      and angiogenesis of tumor. METHOD: The immunohistochemical technique was used to
      detect the expressions of ECM1 and VIII factor in 33 cases of laryngeal tumors.
      RT-PCR technology was used to test the existence of ECM1 mRNA in both fresh
      laryngeal tissue and its surrounding tissue (total 5 cases). RESULT: ECM1 is
      expressed in both benign and malignant laryngeal tissues, chiefly in the cellular
      plasma. But the expression of ECM1 (P<0.01) is significant different between
      benign and malignant laryngeal tumors. Their expressions are stronger in
      malignant tissues than in benign ones. In malignant laryngeal tissue, the
      expression of ECM1 is associated significantly with microvessel density (MVD)
      (24. 50 +/- 5.96) (Spearman's rho is 0. 505, P <0.05). ECM1 mRNA is found in both
      laryngeal carcinoma tissue and its surrounding tissue and it seemed no
      difference. CONCLUSION: ECM1 played an important role in the growth, metastasis
      and angiogenesis of laryngeal carcinoma. The further investigation of ECM1 will
      benefit the treatment of laryngeal carcinoma and the judgement of its prognosis.

PMID- 16646404
TI  - [The clinical significance of the expression of p63 gene in laryngeal squamous
      cell carcinoma].
AB  - OBJECTIVE: To study the expression and clinical significance of p63 gene in
      laryngeal squamous cell carcinoma(LSCC). METHOD: The immunohistochemical
      technique was used to detected the expression of p63 in 63 cases of LSCC, 45
      cases of para-cancer tissues, 24 cases of lymph node metastasis, 40 cases of non
      lymph node metastasis and 25 normal tissues. RESULT: The positive overexpression
      rate of the p63 gene in LSCC (95.24%) and in matched metastatic lymph node
      (83.3%) was significantly higher than para cancer tissues, non metastasis lymph
      node and normal tissues (P<0.01). p63 gene expression was not correlation with
      the clinical stages,clinical typing and pathological classification of the LSCC(P
      >0.05). CONCLUSION: p63 gene had important clinic significance to the diagnosis
      and differential diagnosis of the LSCC. It perhaps participate in regulation of
      tumorigenesis in LSCC, and it may play negative feedback action in the
      development of LSCC.

PMID- 16646405
TI  - [Children's bronchoscopy and bronchoalveolar lavage on endogenic foreign body in
      bronchus].
AB  - OBJECTIVE: To investigate the clinical effect of Children's bronchoscopy and
      bronchoalveolar lavage on endogenic foreign body in bronchus. METHOD: (1) Three
      hundred and thirty-seven cases had bronchoscopy and bronchoalveolar lavage whose
      chest X-ray diagnoses were bronchopneumonia with one or two lobe emphysema and/or
      pulmonary atelectasis, in which 22 cases had severe pneumonia with heart failure
      and respiratory failure. All cases had no history of foreign bodies' inhalation
      and become more dyspnea after a three-day treatment of antibiotics. Three
      hundreds and thirty one cases of bronchoalveolar lavages were divided into two
      groups randomly using saline or azythromycin, saline group had 126 cases (aged 0
      approximately 10 years, mean age, 3 years ); azithromycin group had 211
      cases(aged 0 approximately 8 years, mean age, 3.1 years). RESULT: There were 331
      cases of endotracheal endogenous purulent emboli, 126 cases in left lung, 178 in
      right, and 27 cases in both sides. Judging from nature of emboli, 305 cases were
      mucus, 4 cases were milk valve, 22 cases were white membrane of plastic
      bronchitis. In azithromycin group, 172 cases (81.2%) were cured, 39 cases (18.
      8%) showed effective, the total effective rate was 100 percent. In saline group,
      96 cases were cured, 24 cases showed effective, the total effective rate was 100
      percent. There wasn't statistically significant between two groups in total
      effective rate. The average hospitalization time had a statistical significance
      between saline group (11 days) and azithromycin group (6 days). Two cases of
      complication of pneumothorax happened in operation. They recovered through closed
      drainage of thoracic cavity and 3 cases dead. CONCLUSION: Bronchoscopy and
      bronchoalveolar lavage could shorten the course of endogenic foreign body in
      bronchus; especially it has significance to those cases of respiratory path
      obstruction with heart and respiratory failure. Plastic bronchitis could be
      determined by bronchoscopy and a pathologic histologic examination thereafter.

PMID- 16646406
TI  - [Relationship between CD105 and angiogenesis and biological behaviors in squamous
      carcinoma of larynx].
AB  - OBJECTIVE: To investigate the expression of CD105 in angiogenesis of laryngeal
      squamous carcinoma and in its biological behaviors significance. METHOD: To use
      double staining of immunohistochemistry for CD34/Ki67 and CD105/Ki67 in 30
      laryngeal carcinomas and 10 normal mucosae respectively. Anti CD34 Mb and anti
      CD105 Mb were used to count microvessel density (MVD), respectively. Anti Ki67 Mb
      marked proliferous endothelium cell. The results were analyzed in relation to the
      clinical data. RESULT: It revealed that higher levels of MVDCD105 in tumor tissue
      was observed than in normal samples(P<0.05). Proliferation index (PI) marked by
      CD105 was higher than that marked by CD34(P<0.01). A significant difference
      between high grade of differentiation and low grade of differentiation was found
      in MVDCD34 or MVDCD105 (P<0.05, both). There was no significant difference
      between lymph node metastasis and MVDCD34 or MVDCD105 (P>0.05). MVDCD105
      increased along with increased tumor aggressiveness(P<0.01) and elevated clinical
      stages (P<0.01), but there was no correlation between MVDCD34 and tumor
      aggressiveness, clinical stages(P>0.05). CONCLUSION: CD105 is a differential
      marker of newly angiogenic blood vessel. The newly angiogenic blood vessel
      density was associated with tumor size and clinical stages, but not with lymph
      node metastasis.

PMID- 16646407
TI  - [An analysis of the causes of refractory pharyngeal paraesthesia in 600 cases].
AB  - OBJECTIVE: To investigate the causes of refractory pharyngeal paraesthesia.
      METHOD: Besides routine examination of otolaryngology, 600 patients were tested
      by fiberoptic laryngoscopy, fiberoptic gastroesophagoscopy, nasal sinuses CT,
      styloid process X-ray as well as neck and thyroid gland B ultrasonography. Then,
      they were treated according to respective causes. RESULT: Among 600 cases of
      refractory pharyngeal paraesthesia, 229 (38.2%) cases were diagnosed as
      gastroesophagitis, 113 (18.8%) nasal sinusitis, 57 (9.5%) climacteric syndromes,
      40 (6.7%) chronic tonsillitis, 22 (3.7%) carcinophobia, 13 (2.2%) subacute
      thyroiditis or thyrophymas, 9 (1.5%) elongation of styloid process and 117
      (19.5%) other causes. All patients were treated according to respective causes
      and total cure rate was 84.2% after 6 months. CONCLUSION: There are many causes
      of pharyngeal paraesthesia. We should pay attention to its relationship with
      gastroesophagitis and nasal sinusitis etc, especially, gastroesophageal reflux
      disease.

PMID- 16646408
TI  - [Expression of aquaporin 1 and aquaporin 4 in rat laryngeal tissue].
AB  - OBJECTIVE: To detect expression level and distribution of aquaporin 1(AQP1) and
      aquaporin 4 (AQP4) in rat laryngeal tissues and try to find out significance
      about aquaporin in the laryngeal function and mechanism on the laryngeal
      diseases. METHOD: Eight cases laryngeal tissues were obtained from normal wistar
      rats. The slides were detected with HE staining for routine histopathologic
      examination, immunohistochemical staining was performed for observing the
      expression of AQP1 and AQP4 in laryngeal tissue. RESULT: AQP1 expresses mainly on
      the capillary endothelial cell of laryngeal mucous lamina propria, laryngeal
      mucous glands and myocyte nuclear membrane. AQP4 expresses mainly on squamous
      epithelial, pseudostratified ciliated columnar epithelium, laryngeal lamina
      propria mucous glands and myocyte membrane. CONCLUSION: The distribution of
      Aquaporin 1 and aquaporin 4 on rat laryngeal tissue is dramatically different.
      This result suggests that they may have different role on the water transport of
      larynx, and may play an important role on laryngeal diseases.

PMID- 16646409
TI  - Hopefully, a short-lived record.

PMID- 16646410
TI  - Fluoridation.

PMID- 16646411
TI  - Volunteers bring smiles all across the globe.

PMID- 16646412
TI  - Oral pathology quiz # 50. Case number 1. Pemphigus vulgaris.

PMID- 16646413
TI  - One dentist's opinion: the state of dental insurance.

PMID- 16646414
TI  - [Combination products: a new model of medical devices].
AB  - A combination product is a new model of the medical product that incorporates at
      least two of the regulated component categories of device, drug, or biological
      product into one product. It has become a new hot point within the development of
      devices and drugs, and has brought about a new opportunity for device and drug
      industries and a new challenge for administration too. In the paper, the
      properties of combination products are summed up and the impact on device and
      drug industries are discussed.

PMID- 16646415
TI  - [Study on surface modification and biocompatibility of NiTi alloy intravascular
      stents].
AB  - This paper introduces the surface modification of NiTi alloy intravascular stents
      for roughness by chemical erosion and plasma deposition technology. The stent
      which had been granulated with chemical erosion was treated with TiO2 film
      prepared with Gel-sol. The study on the biocompatibility of the modified stent by
      the above two ways shows that the modified stent is rougher, and its
      anticoagulation and hydrophilicity are improved. However, the capability of
      erosion resistance is not enhanced significantly.

PMID- 16646416
TI  - [Geometric active contour model with color and intensity priors for medical image
      segmentation].
AB  - A new algorithm using the geometric active contour model with the fusion of color
      and intensity priors to segment medical images is presented in this paper. The
      prior knowledge used here are firstly defined in different color spaces and
      represented as thresholds searched by the genetic algorithm. Then the prior
      knowledge is merged into active contour model with its contour evolution by the
      level set technique. The experiments on clinical marrow images and mammograms
      have successfully demonstrated its superiority of the proposed algorithm over the
      existing active contour models which deal with image gradient information.

PMID- 16646417
TI  - [Wavelet threshold denoising algorithm for CR images].
AB  - A wavelet threshold denoising algorithm for CR images is put forward here . A
      noised CR image is decomposed into wavelet coefficients, which are processed by
      the algorithm, and the denoised CR image is reconstructed based on the processed
      coefficients. Examples are too presented to demonstrate the efficiency of the
      algorithm on denoising and, maintaining the detail of the CR images.

PMID- 16646418
TI  - [An invariant approach for image registration in digital subtraction
      angiography].
AB  - In modern medicine, DSA is a powerful technique in visualizations of blood
      vessels of X-ray images. In DSA, the most important way for motion correction is
      image registration. In this paper, a new approach to the registration is used. It
      is based on means of template matching according to a combined invariants-based
      similarity measure and TPS image warping. Furthermore it has been improved
      through practice. and tests have proved to remove the motion artifacts
      effectively and rapidly.

PMID- 16646419
TI  - [A method for extracting basic rhythms of EEG via wavelet analysis].
AB  - As basic electrophysiology signals of a human being, electroencephalogram (EEG)
      has been widely used in researches and clinics. The paper proposes a method for
      extracting rhythms of EEG, based on wavelet analysis. By using Daubechies mother
      wavelet, raw EEG is decomposed, and then we extract basic rhythms of EEG after
      interference is eliminated insome scales. This method not only eliminates
      interference well, but also extracts rhythms perfectly.

PMID- 16646420
TI  - [Medical product designing model for the "BOP" in China].
AB  - China has a large population under the average economy. This group of people is
      often referred to those at the Bottom of the Pyramid (BOP). In order to meet
      their special medical needs, this paper is to discuss a topic on how to create
      medical products for the "BOP" in China, especially under sustainable
      developments based on the investigation and analysis in Shanghai. Also, a new
      possible development model including the government's support, knowledge exchange
      and communication is introduced.

PMID- 16646421
TI  - [The design of the external defibrillator using the truncated exponential
      biphasic waveform].
AB  - The external defibrillator is an emergency instrument used very widely in
      clinics. It plays an important role in rescuing ventricle fibrillation (VF)
      patients. We have designed an external defibrillator using the truncated
      exponential biphasic waveform. The system consists of three parts: the ECG
      collection module, the control module and the defibrillator module. They are
      introduced respectively, listing the main problems and the methods to solve them.
      Some experiments have been done and the corresponding results are given.

PMID- 16646422
TI  - [Development of a portable glucose meter based on PIC microcomputer].
AB  - A portable glucose meter based on PIC microcomputer with data storage, analysis
      and historical data curve display functions, is presented. The concentration of
      blood glucose is detected with a glucose oxidase electrode. Test records may be
      stored and historic data can be displayed on the LCD with a fitting curve.

PMID- 16646423
TI  - [Design and manufacture of microneedles array for transdermal drug delivery].
AB  - It is very important to disrupt the stratum corneum structure and to create
      pathways allowing transport of macromolecules, as the traditional transdermal
      drug delivery has been severely limited by the skin barrier. With the development
      of the Micro Electro-Mechanical System (MEMS), it becomes possible for
      microneedles array to strengthen the transdermal drug delivery. In addition to
      the increase of the skin permeability, it can also be used to deliver drugs into
      skin, such as insulin and vaccine, providing a new direction for drug delivery
      systems. In this paper, we review the development and applications in transdermal
      drug delivery of microneedles' array. The commercial prospects and
      recommendations for the future research work are also represented.

PMID- 16646424
TI  - [Development of measurement and control technologies for hyperthermia treatments
      of tumors with AC magnetic field].
AB  - Hyperthermia therapy with AC magnetic field heating magnetic nanoparticles is a
      new kind of treatment method. The paper reviews the research progresses about AC
      magnetic heating setups for hyperthermia therapy measurements of magnetic field
      temperature control, and so on.

PMID- 16646425
TI  - [Better medical devices regulations for better health care: enlightenment for
      medical devices regulatory reform in China, from experiences of the E.U. and the
      U.S.A].
AB  - The expansion of applications of medical devices has attracted the increased
      attention of government regulatory bodies around the world to the safety and
      effectiveness of these products. Most developed countries, such as the United
      States and European Union, have developed well-established regulatory systems for
      medical devices, which have also consistently been amended to accommodate the
      changing requirements of safety and the trend of globalization.The current
      "Regulations for the Supervision and Administration of Medical Device (China)",
      established in 2000, has brought about great improvements for the safety and
      effectiveness of products, safeguarding public health. But there are still, at
      present, a lot of counterfeit and poor quality devices and device-related adverse
      events for lack of powerful post -market and in-use regulatory controls for
      products. It is therefore very urgent for the Chinese government to reform its
      medical device administration and management. This research paper analyses and
      compares the different requirements and executions of medical devices regulations
      in the EU, the US and China, to draw some experiences of the EU and US regimes
      that are very useful to China's regulatory reform. It is suggested that when
      developing a new scheme of medical devices regulatory reform in China, two
      prominent aspects have to be considered by policy makers and regulators. Firstly,
      the global trend of medical devices regulations has to be taken into account.
      Secondly, the experiences learned from the EU and US systems should be applied to
      the Chinese regulatory reform in combination with the concrete practice of China.

PMID- 16646426
TI  - [The AHP of criteria analysis weighting for assessment on medical equipment
      suppliers].
AB  - In order to improve the management of the supplier chain, it is necessary to
      setup a assessment system on suppliers. The assessment includes lot's of criteria
      such as quality, cost, service and delivery capabilities. The different criteria
      should have different weighting. The AHP method is chosen here in the paper to
      analyse the weighting of individual criteria.

PMID- 16646427
TI  - [Grounding technique for the safety and noise rejection of medical imaging
      equipments].
AB  - Grounding technique is very important to ensure the human safety, imaging
      devices' safety and the devices' reliable running. This paper expatriates the
      principles of the grounding safety, interference rejection earth, and the
      grounding modes and the mode selection for each imaging devices and equipments,
      and related grounding requirements.

PMID- 16646428
TI  - [Collection of cardiac self-gated signals based on TrueFisp sequence].
AB  - The paper introduces a method of self-gated signal's collection based on TrueFisp
      sequence, during self-gated cardiac magnetic resonance imaging. There is no
      significant difference in its image quality and only a slight loss in efficiency
      in comparison with MRI images by ECG-based triggering.

PMID- 16646430
TI  - Valuing Web usage.

PMID- 16646429
TI  - [An intelligent photoelectric oxygen-inhalation calculagraph].
AB  - This paper introduces a self-made intelligent oxygen-inhalation accumulative
      calculagraph. A photoelectric probe is fixed on the buoy of the oxygen flowmeter
      under non-ventilation conditions.When the oxygen flowmeter is switch on, the buoy
      floats up, the oxygen supply begins and the timing starts at the same time. When
      oxygen inhalation pauses, the buoy goes down and the timing stops. When oxygen
      inhalation starts again, the timing continues and accumulates.

PMID- 16646431
TI  - Can drugs found in water harm humans?

PMID- 16646432
TI  - Linking China's air pollution to exports.

PMID- 16646433
TI  - Polystyrene to biodegradable PHA plastics.

PMID- 16646434
TI  - Perfluorinated chemicals in blood.

PMID- 16646435
TI  - Climate change and American exceptionalism.

PMID- 16646436
TI  - Controversy flares over rice research.

PMID- 16646437
TI  - New recycling process recovers plastics from end-of-life vehicles.

PMID- 16646438
TI  - American exceptionalism? Similarities and differences in national attitudes
      toward energy policy and global warming.
AB  - Despite sharp differences in government policy, the views of the U.S. public on
      energy and global warming are remarkably similar to those in Sweden, Britain, and
      Japan. Americans do exhibit some differences, placing lower priority on the
      environment and global warming, and with fewer believing that "global warming has
      been established as a serious problem and immediate action is necessary". There
      also remains a small hard core of skeptics (< 10%) who do not believe in the
      science of climate change and the need for action, a group that is much smaller
      in the other countries surveyed. The similarities are, however, pervasive.
      Similar preferences are manifest across a wide range of technology and fuel
      choices, in support of renewables, in research priorities, in a basic
      understanding of which technologies produce or reduce carbon dioxide (or
      misunderstandings in the case of nuclear power), and in willingness to pay for
      solving global warming.

PMID- 16646439
TI  - Modeling study of air pollution due to the manufacture of export goods in China's
      Pearl River Delta.
AB  - The Pearl River Delta is a major manufacturing region on the south coast of China
      that produces more than dollar 100 billion of goods annually for export to North
      America, Europe, and other parts of Asia. Considerable air pollution is caused by
      the manufacturing industries themselves and by the power plants, trucks, and
      ships that support them. We estimate that 10-40% of emissions of primary SO2,
      NO(x), RSP, and VOC in the region are caused by export-related activities. Using
      the STEM-2K1 atmospheric transport model, we estimate that these emissions
      contribute 5-30% of the ambient concentrations of SO2, NO(x), NO(z), and VOC in
      the region. One reason that the exported goods are cheap and therefore attractive
      to consumers in developed countries is that emission controls are lacking or of
      low performance. We estimate that state-of-the-art controls could be installed at
      an annualized cost of dollar 0.3-3 billion, representing 0.3-3% of the value of
      the goods produced. We conclude that mitigation measures could be adopted without
      seriously affecting the prices of exported goods and would achieve considerable
      human health and other benefits in the form of reduced air pollutant
      concentrations in densely populated urban areas.

PMID- 16646440
TI  - Electron microbeam investigation of uranium-contaminated soils from Oak Ridge,
      TN, USA.
AB  - Two samples of uranium-contaminated soil from the Department of Energy's Oak
      Ridge Reservation in Oak Ridge, Tennessee were investigated using electron
      microprobe analysis and transmission electron microscopy. The objectives of this
      research were to identify and characterize soil particles and rock chips with
      high uranium concentrations, to investigate the extent of uranium penetration
      into chips of parent material, and to identify solid-phase hosts for uranium in
      the samples. Three distinct solid-phase hosts for uranium have been identified:
      (1) iron oxyhydroxides, including goethite and ferrihydrite; (2) mixed Mn-Fe
      oxides; and (3) discrete uranium phosphates. In all three, uranium is associated
      with phosphorus. The ubiquitous U-P association highlights the influence of
      phosphate on the environmental fate of uranium. Uranium-bearing phases are found
      well within chips of weathered shale, as far as 900 microm from fractures and
      chip edges, indicating that uranium has diffused into the shale matrix.

PMID- 16646441
TI  - Change of dissolved gaseous mercury concentrations in a southern reservoir lake
      (Tennessee) following seasonal variation of solar radiation.
AB  - A 12-month field study was conducted consecutively from June 2003 to May 2004 to
      quantify temporal variations of dissolved gaseous mercury (DGM) concentrations in
      Cane Creek Lake, a southern reservoir lake (Cookeville, TN). Diurnal changes of
      DGM concentrations in two periods (morning increase vs afternoon decrease with an
      around-noon peak) were observed, and the changes closely followed daily solar
      radiation variation trends. The diurnal patterns prevailed in the late spring and
      summer, but became vague in the late fall and winter. The monthly mean DGM
      concentrations peaked at 40.8 pg L(-1) in July and reached the lowest at 14.2 pg
      L(-1) in December and 21.9 pg L(-1) in January; this DGM concentration change
      closely followed the monthly mean solar radiation variation trend. The increase
      of the lake DGM concentration from January to July and its decrease from July to
      December mirror the typical daily rhythm of DGM concentration variations in the
      two periods. This finding supports the following hypothesis: The natural
      phenomenon of daily oscillation of freshwater DGM concentrations that follows
      diurnal solar radiation variation would manifest on a seasonal scale. High DGM
      concentrations were found in the spring and summer and low in the fall and winter
      (seasonal mean: 34.2, 37.5, 20.0, 24.4 pg L(-1), respectively). This seems to
      suggest an annual occurrence of two periods of the seasonal DGM level fluctuation
      (spring and summer high vs fall and winter low DGM levels). Linear relationships
      of the monthly mean DGM concentrations were found with the monthly mean global
      solar radiation (R2 = 0.82, P < 0.05) and UVA radiation (R2 = 0.84, P < 0.05).
      Linear relationships of the seasonal mean DGM concentrations were also found with
      the seasonal mean global solar radiation (R2 = 0.85, P = 0.08) and UVA radiation
      (R2 = 0.93, P < 0.05).

PMID- 16646442
TI  - Organophosphorus insecticides in agricultural and residential runoff: field
      observations and implications for total maximum daily load development.
AB  - Development of total maximum daily loads (TMDLs) for nonpoint source pollutants
      requires mass flux estimates for targeted compounds from contributing sources. We
      measured organophosphorus insecticide concentrations in surface runoff from
      agricultural and residential land-use sites in a southern Californian watershed
      over the course of runoff-producing irrigation and rainfall events. Event mean
      concentrations (EMCs) for chlorpyrifos, diazinon, and malathion exhibited
      considerable variability among irrigation and storm runoff events at agricultural
      sites; residential storm runoff EMCs for these compounds were considerably less
      variable. Event loads and EMCs were higher for runoff events following reported
      insecticide applications. Organophosphorus insecticide EMCs were not consistently
      correlated with hydrologic characteristics of runoff events. Our results indicate
      that on an area basis, loads from residential land may exceed those from sites
      planted in row crops for a given rainfall depth, suggesting that residential land
      use warrants explicit consideration in TMDL development and implementation. No
      consistent first flush effect was discernible for organophosphorus insecticides
      in storm or irrigation runoff. A relative potency factor approach is introduced
      to permit evaluation of organophosphorus insecticides on a common toxicological
      basis and allow development of TMDLs and pollutant control strategies for these
      compounds as a class.

PMID- 16646443
TI  - Perfluorochemicals in pooled serum samples from United States residents in 2001
      and 2002.
AB  - Manufacturers have used perfluorochemicals (PFCs) since the 1950s in many
      industrial and consumer products, including protective coatings for fabrics and
      carpet, paper coatings, insecticide formulations, and surfactants. Some PFCs are
      persistent ubiquitous contaminants in the environment and in humans. Exposures to
      PFCs result in potential developmental and other adverse effects in animals. The
      sources of human exposure to PFCs and the potential health risks associated with
      exposure are still unclear, and differences in patterns of human exposure may
      vary. We measured the serum concentrations of perfluorooctane sulfonic acid
      (PFOS), perfluorooctanoic acid (PFOA; C8), perfluorohexane sulfonic acid (PFHxS),
      and 8 other PFCs in 54 pooled serum samples collected from 1832 participants of
      the 2001-2002 National Health and Nutrition Examination Survey. Participants were
      12 years of age and older. The pools represented three major racial
      groups/ethnicities (non-Hispanic blacks, non-Hispanic whites, and Mexican
      Americans), four age categories (12-19 years, 20-39 years, 40-59 years, and 60
      years and older), and both genders. PFCs were extracted from 100 microL of serum
      using on-line solid-phase extraction coupled to isotope dilution-high performance
      liquid chromatography-tandem mass spectrometry. The limits of detection ranged
      from 0.05 ng/mL to 0.2 ng/mL. The concentrations of most PFCs were similar among
      the four age groups. For PFOS, the estimated least-squares mean (LSM)
      concentrations among non-Hispanic white males (40.19 ng/mL) and females (23.97
      ng/mL) were greater than among non-Hispanic black males (18.27 ng/mL) and females
      (17.93 ng/mL) or Mexican American males (13.71 ng/mL) and females (10.40 ng/ mL).
      Similarly, for PFOA, the LSM concentrations among non-Hispanic white males (6.98
      ng/mL) and females (3.97 ng/ mL) were greater than among non-Hispanic black males
      (3.62 ng/mL) and females (2.85 ng/mL) or Mexican American males (2.89 ng/mL) and
      females (2.08 ng/mL). Non-Hispanic whites had also greater LSM concentrations of
      PFHxS than non-Hispanic blacks and Mexican Americans. These findings indicate
      different patterns of human exposure to PFCs among the population groups examined
      and stress the importance of conducting research to identify the environmental
      sources and pathways of human exposure to PFCs.

PMID- 16646444
TI  - Temporal and spatial trends of organochlorine pesticides in Great Lakes
      precipitation.
AB  - Organochlorine pesticide concentrations in precipitation samples collected from
      1997 to 2003 at seven Integrated Atmospheric Deposition Network sites around the
      Great Lakes are reported. The 28-day volume weighted mean concentrations of
      several pesticides, including gamma-hexachlorocyclohexane (HCH), endosulfan,
      hexachlorobenzene, chlordane, and DDE, showed significant seasonal trends. For
      current-use pesticides (endosulfan and gamma-HCH), their concentrations peaked in
      late spring to summer just after their agricultural application. For the banned
      pesticides, higher concentrations were observed in the winter due to their
      enhanced partitioning to particles and scavenging by snow. Long-term decreasing
      trends were observed for several pesticides such as gamma-HCH and DDE. On the
      other hand, beta-HCH showed significant increasing concentrations as a function
      of time at Brule River, Eagle Harbor, and Sleeping Bear Dunes. Generally, Chicago
      had the highest concentration of chlordanes, dieldrin, and DDT, indicating that
      urban areas could be a source for these compounds to precipitation. For gamma-HCH
      and endosulfans, Point Petre had the highest concentrations due to the
      application of these pesticides in the surrounding areas.

PMID- 16646445
TI  - Spray irrigation of treated municipal wastewater as a potential source of
      atmospheric PBDEs.
AB  - Spray irrigation facilities utilizing treated municipal wastewater are a
      potential source of polybrominated diphenyl ethers (PBDEs) to the atmosphere.
      PBDEs are used as flame retardants in many household items and have been found in
      wastewaters and biosolids. Evidence of PBDE release from spray irrigation
      facilities was discovered during a multiyear project to measure semivolatile
      organic chemical concentrations in air. Four BDE congeners (47, 99, 100, and 154)
      were monitored at three remote/ rural locations in Maryland and Delaware from
      2001 to 2003. Average concentrations at two of the sites (BDE-47, 10-17 pg/m3;
      BDE-99, 5.3-7.7 pg/m3) reflect background levels. Average concentrations at the
      third location were 5-10 times higher (BDE-47, 175 pg/m3; BDE-99, 26 pg/m3) and
      were significantly correlated (p < 0.0001) with temperature indicating local
      source(s). Several spray irrigation facilities are located south and west of the
      third site, the prevailing wind direction during the spring and summer when most
      samples were collected. The fine mist released from the irrigation equipment may
      enhance release to the atmosphere via air-water gas exchange from water droplets.
      Temporal trends indicate that aerial concentrations of PBDEs in this area are
      increasing at an exponential rate; the atmospheric doubling times for the
      different congeners range from 1.1 to 1.7 yrs.

PMID- 16646446
TI  - Dispersion modeling as a dioxin exposure indicator in the vicinity of a municipal
      solid waste incinerator: a validation study.
AB  - Whether low environmental doses of dioxin affect the general population is the
      matter of intense debate and controversy. In a previous study, we found a 2.3
      fold risk for non-Hodgkin lymphoma associated with residence in areas classified
      as highly exposed to dioxin emitted from a municipal solid waste incinerator
      (MSWI) (Besancon, France). The main limitation lay within the use of a first
      generation Gaussian-type dispersion model as a proxy for dioxin exposure, since
      its accuracy had not been assessed before. The aim of this study was to validate
      this geographic-based exposure through PCDD/F measurements from soil samples.
      PCDD/F concentration, pH, organic carbon concentration, cation exchange capacity,
      and geomorphology and ecology features were assessed for 75 sampling points. In
      simple terrain (i.e. northeast of the MSWI), a significant association was
      highlighted between modeled dioxin ground-level air concentrations and log
      transformed measured dioxin soil concentrations with a strong gradient across
      exposure categories. Conversely, in a complex topography situation (i.e.
      southwest of the MSWI), the model overpredicted ground-level air concentrations,
      particularly in the high exposure zone. First-generation modeling provided a
      reliable proxy for dioxin exposure in simple terrain, reinforcing the results of
      our case-control study. However, a more advanced atmospheric diffusion model
      should have been used for refined assessment in complex terrain.

PMID- 16646447
TI  - Size-based speciation of natural colloidal particles by flow field flow
      fractionation, inductively coupled plasma-mass spectroscopy, and transmission
      electron microscopy/X-ray energy dispersive spectroscopy: colloids-trace element
      interaction.
AB  - Flow field flow fractionation (FIFFF), inductively coupled plasma-mass
      spectroscopy (ICP-MS), and transmission electron microscopy (TEM) coupled to X
      ray energy dispersive spectrometry (X-EDS) are used in series for the first time
      to characterize colloids. Results demonstrate the utility of FIFFF-ICP-MS-TEM/X
      EDS to relate physical properties (size) of colloids to their chemical properties
      (chemical composition, surface chemical composition, and colloids-trace elements
      association). Results suggest that the major part of natural organic matter (NOM)
      is concentrated in the fraction < 0.01 microm (C2). Aluminum, iron, and manganese
      are the main colloidal components in the fraction 0.01-0.45 microm (C1). Aluminum
      occurs as aluminum oxides or aluminosilicates in the whole size range, while iron
      and manganese occur as individual oxyhydroxides in the size range < 0.20 microm.
      Within the C2 fraction, Al, Mn, Cu, and Ni elements are complexed to NOM (e.g.,
      humic substances). Iron is complexed to NOM in some samples and probably free in
      other samples. Lead is totally free in all samples. Within the C1 fraction, Cu
      and Pb are mostly associated to Fe and Mn oxyhydroxides. Consequently, NOM with
      Fe and Mn oxyhydroxides are the main colloidal carriers of trace elements in the
      Loire watershed system.

PMID- 16646448
TI  - Evaluation of urinary methoxyphenols as biomarkers of woodsmoke exposure.
AB  - Urinary methoxyphenols have been proposed as biomarkers for woodsmoke exposure,
      but the relationship between exposure and urinary methoxyphenol concentrations
      has not been characterized. We collected personal particulate matter2.5 and urine
      samples from 9 adults experimentally exposed to smoke from an open wood fire to
      characterize this relationship. Personal exposures (PM2.5 mean 1500 microg/ m3)
      varied 3.5-fold. Twenty-two methoxyphenols, levoglucosan, and 17 polynuclear
      hydrocarbons were quantified by gas chromatography/mass spectrometry assays for
      personal filter samples and urine samples. Most methoxyphenols had measurable
      preexposure levels. Propylguaiacol, syringol, methylsyringol, ethylsyringol, and
      propylsyringol had peak urinary concentrations after the woodsmoke exposure.
      Eight subjects had peak urinary elimination of methoxyphenols within 6 h (t1/2 3
      5 h), whereas one had delayed elimination. Several metrics for urinary excretion
      were evaluated. Analyte concentration was greatly affected by diuresis. Excretion
      rate and analyte concentrations normalized by creatinine gave a clearer signal
      and were equivalent in predictive ability. Twelve-hour average creatinine
      normalized concentrations of each of the 5 methoxyphenols gave a Pearson
      correlation > or = 0.8 with their particle-phase concentration. The sum of
      urinary concentrations for the 5 methoxyphenols versus levoglucosan on personal
      filters gave a regression coefficient of 0.75. This sum versus PM2.5 gave a
      regression coefficient of 0.79. The intercept of this regression suggests that
      the threshold for detection of an acute exposure event would be approximately 760
      microg/m3 particulate matter from woodsmoke. The signal-to-noise (12-h
      postexposure average/preexposure average) ranged from 1.1 to 8 for the 5
      methoxyphenols. Analysis of multiple compounds provided assurance that elevations
      were not artifactual due to food or other products.

PMID- 16646449
TI  - Direct and indirect atmospheric deposition of PCBs to the Delaware River
      watershed.
AB  - Atmospheric deposition can be an important source of PCBs to aquatic ecosystems.
      To develop the total maximum daily load (TMDL) for polychlorinated biphenyls
      (PCBs) for the tidal Delaware River (water-quality Zones 2-5), estimates of the
      loading of PCBs to the river from atmospheric deposition were generated from
      seven air-monitoring sites along the river. This paper presents the atmospheric
      PCB data from these sites, estimates direct atmospheric deposition fluxes, and
      assesses the importance of atmospheric deposition relative to other sources of
      PCBs to the river. Also, the relationship between indirect atmospheric deposition
      and PCB loads from minor tributaries to the Delaware River is discussed. Data
      from these sites revealed high atmospheric PCB concentrations in the
      Philadelphia/Camden urban area and lower regional background concentrations in
      the more remote areas. Wet, dry particle, and gaseous absorption deposition are
      estimated to contribute about 0.6, 1.8, and 6.5 kg year-(-1) sigmaPCBs to the
      River, respectively, exceeding the TMDL of 0.139 kg year(-1) by more than an
      order of magnitude. Penta-PCB watershed fluxes were obtained by dividing the
      tributary loads by the watershed area. The lowest of these watershed fluxes are
      less than approximately 1 ng m(-2) day(-1) for penta-PCB and probably indicates
      pristine watersheds in which PCB loads are dominated by atmospheric deposition.
      In these watersheds, the pass-through efficiency of PCBs is estimated to be on
      the order of 1%.

PMID- 16646450
TI  - Levels of the flame retardants hexabromocyclododecane and tetrabromobisphenol A
      in the blubber of harbor porpoises (Phocoena phocoena) stranded or bycaught in
      the U.K., with evidence for an increase in HBCD concentrations in recent years.
AB  - Within the U.K. Marine Mammals Stranding Program, analysis of brominated flame
      retardants began in 1999. Initially, the focus of attention was the brominated
      diphenyl ethers. Since the withdrawal of the pentamix and octamix polybrominated
      diphenyl ether (PBDE) formulations from the EU market prior to August 2004, two
      other high-volume products, hexabromocyclododecane (HBCO) and tetrabromobisphenol
      A (TBBP-A), have been included. We report the concentrations of these compounds
      in the blubber of harbor porpoises (Phocoena phocoena) stranded or dying due to
      physical trauma in the U.K. during the period 1994-2003. Analysis was undertaken
      using LC/MS method on a diastereoisomer basis. Eighty-five samples were analyzed
      for HBCD, and 68 of these for TBBP-A. alpha-HBCD dominated over the other isomers
      and was detected in all samples analyzed at concentrations ranging from 10 to 19
      200 microg kg(-1) wet weight. The maximum concentration was about double that
      reported in earlier U.K. studies. TBBP-A was detected in only 18 samples and at
      much lower concentrations, from 6 to 35 microg kg(-1) wet weight. Investigation
      of possible time trends indicated a sharp increase in HBCD concentrations from
      about 2001 onward, which was not confounded by age (length), sex, nutritional
      status, or location. This may be a result of changing patterns of use of HBCD
      following limitations on the production and use of two PBDE formulations within
      the EU and will feed ongoing risk assessment activities.

PMID- 16646451
TI  - Freely dissolved pore water concentrations and sorption coefficients of PAHs in
      spiked, aged, and field-contaminated soils.
AB  - Freely dissolved aqueous concentrations in the soil pore water represent an
      important aspect of bioavailability and risk assessment of contaminated soils. In
      this study, a negligible depletive partitioning based sampling technique was
      validated and applied to measure free concentrations of polycyclic aromatic
      hydrocarbons (PAHs) in spiked, aged and field-contaminated soils. Detailed
      kinetic studies were performed to select appropriate equilibration times. Freely
      dissolved aqueous concentrations in the pore water were compared to total
      concentrations, and sorption coefficients were calculated. Results show that
      equilibrium partition models can predict sorption coefficients of freshly spiked
      and lab-aged soils rather accurately. However, freely dissolved pore water
      concentrations of field-contaminated soils are orders of magnitude lower than
      model predictions. Consequently, environmental risks can be highly overestimated
      with these models. The simple and sensitive partitioning-based sampling technique
      used in this study, could, therefore, be applicable to improve site-specific risk
      assessment of field-contaminated soils.

PMID- 16646452
TI  - Semicontinuous measurements of organic carbon and acidity during the Pittsburgh
      Air Quality Study: implications for acid-catalyzed organic aerosol formation.
AB  - Laboratory evidence suggests that inorganic acid seed particles may increase
      secondary organic aerosol yields secondary organic aerosol (SOA) through
      heterogeneous chemistry. Additional laboratory studies, however, report that
      organic acidity generated in the same photochemical process by which SOA is
      formed may be sufficient to catalyze these heterogeneous reactions. Understanding
      the interaction between inorganic acidity and SOA mass is important when
      evaluating emission controls to meet PM2.5 regulations. We examine semicontinuous
      measurements of organic carbon (OC), elemental carbon (EC), and inorganic species
      from the Pittsburgh Air Quality Study to determine if we can detect coupling in
      the variations of inorganic acidity and OC. We were not able to detect
      significant enhancements of SOA production due to inorganic acidity in Western
      Pennsylvania most of the time, but its signal might have been lost in the noise.
      If we assume a causal relationship between inorganic acidity and OC, reductions
      in OC for Western Pennsylvania that might result from drastic reductions in
      inorganic acidity were estimated to be 2 +/- 4% by a regression technique, and an
      upper bound for this geographic area was estimated to be 5 +/- 8% based on
      calculations from laboratory measurements.

PMID- 16646453
TI  - Role of Fe(III), phosphate, dissolved organic matter, and nitrate during the
      photodegradation of domoic acid in the marine environment.
AB  - The photodegradation of domoic acid in model seawater containing varying amounts
      of total Fe(lll) (expressed as Fe(lll)), NO(3-), total phosphate (expressed as
      P04(3-)), and dissolved organic matter (DOM) is reported. A multivariate,
      microscale, high-throughput experimental approach is described for evaluating how
      these components interact to control the removal of domoic acid from natural
      waters. Under the nominal conditions of the study ([Fe(lll)]o 0-4 microM; [N03-]o
      0-35 microM; [P04(3-)]o 0-4 microM; [DOM]o 0-10 mg/ L), it is apparent that
      Fe(lll) and DOM are significant promoters of domoic acid photooxidation. In
      contrast, P04(3-) interacts with Fe(lll) to inhibit the photooxidation of domoic
      acid, but P04(3-) alone does not act to slow or accelerate domoic acid
      photodegradation. No other variables (singly or interactively) have a
      statistically significant impact. At an incident light intensity of 765 W/m2 and
      initial domoic acid concentration of 0.96 microM, domoic acid half-lives range
      over 12-36 h, with half-life a function of [Fe(III)], [PO4(3-)], and dissolved
      organic matter loadings. An NMR based technique for measuring domoic acid-Fe(lll)
      binding (1.72 x 10(11)) is reported.

PMID- 16646454
TI  - Nitroaromatic reduction kinetics as a function of dominant terminal electron
      acceptor processes in natural sediments.
AB  - The reductive transformation of p-cyanonitrobenzene (pCNB) was investigated in
      laboratory batch slurries exhibiting dominant terminal electron accepting
      processes (TEAPs). Pseudo-first-order rate constants (k(obs)) were measured for
      the reduction of pCNB in nitrate-reducing, iron-reducing, sulfate-reducing, and
      methanogenic sediment slurries. Reduction was extremely slow in nitrate-reducing
      slurries but increased in slurries exhibiting TEAPs with significant
      concentrations of solution phase Fe(ll). As the reduction of pCNB progressed in
      the Fe(ll) rich systems, significant but nonstoichiometric decreases in aqueous
      Fe(ll) concentration were measured. Normalization of k(obs) to initial aqueous
      Fe(ll) concentrations (k(obs)/[Fe(ll)]t=0) gave values ranging from 0.0040 to
      0.0052 d(-1) microM(-1) for nitrate-reducing, iron-reducing, and methanogenic
      sediment slurries as well as sulfate-reducing sediment slurries in which lactate
      served as a source of organic carbon. The k(obs)/ [Fe(ll)]t=0 ratios were 1-fold
      greater for sulfate-reducing batch slurries amended with acetate and iron
      reducing slurries equilibrated with a 3% H2 atmosphere indicating that the
      electron source and system parameters such as pH play a determinant role in the
      reaction kinetics. Although these data demonstrate that aqueous phase Fe(ll) must
      be present for significant reduction to occur, a limited role for aqueous phase
      Fe(ll) as a quantitative indicator of reactivity is suggested.

PMID- 16646455
TI  - Bidentate complexation modeling of heavy metal adsorption and competition on
      goethite.
AB  - Accurate sorption modeling is critical for environmental risk assessment and
      development of sound remedial technologies. Adsorption to iron oxide phases is
      one of the important sorption processes regulating the bioavailability and
      toxicity of metal ions in natural systems. In this study, we used
      spectroscopically derived bidentate surface species to constrain surface
      complexation modeling in addressing Ni(ll) and Zn(ll) adsorption and competition
      on goethite surfaces. The 2-pK(a) triple layer model successfully predicted
      adsorption in single adsorbate systems. The curvature in adsorption isotherms was
      accurately depicted using two types of sites: high affinity and low affinity, and
      mononuclear bidentate surface complexes. A constrained set of parameters was
      found for each metal (log K(L) = -6.63 and log K(H) = -2.45 for Ni, log K(L) = 
      3.92 and log K(H) = 2.14 for Zn) that successfully described adsorption over a
      large range of experimental conditions, covering 6 to 7 orders of magnitude in
      concentration, ionic strength from 10(-3) to 10(-2), and environmentally relevant
      pH range between 4 and 6.5. Adsorption competition was predicted using the
      bidentate surface species with parameters calibrated using single adsorbate data.

PMID- 16646456
TI  - A chemical extraction method for mimicking bioavailability of polycyclic aromatic
      hydrocarbons to wheat grown in soils containing various amounts of organic
      matter.
AB  - In this study, we have evaluated the extent to which organic matter contents in
      soils influence the accumulation of PAHs by the roots of wheat plants and have
      developed a rapid chemical method for determining the bioavailability of PAH.
      Four polycyclic aromatic hydrocarbons (PAHs), naphthalene, acenaphthylene,
      fluorene, and phenanthrene, were added to natural soil samples with different
      amounts of organic matterfor pot experiments to evaluate apparent bioavailability
      of PAHs to wheat roots (Triticum aestivum L.). The extractabilities of PAHs in
      the soil were tested by a sequential extraction scheme using accelerated solvent
      extraction with water, n-hexane, and a mixture of dichloromethane and acetone as
      solvents. The water or n-hexane-extractable PAHs were positively correlated to
      dissolved organic matter (DOM) and negatively correlated to total organic matter
      (TOM), indicating mobilization and immobilization effects of DOM and TOM on soil
      PAHs, respectively. The apparent accumulation of PAHs by wheat roots was also
      positively and negatively correlated to DOM and TOM, respectively. As a result,
      there are positive correlations between the amounts of PAHs extracted by water or
      n-hexane and the quantities accumulated in plant roots, suggesting the
      feasibility of using water- or n-hexanes-extractable fractions as indicators of
      PAH availability to plants.

PMID- 16646457
TI  - Sorption and remobilization behavior of 4-tert-octylphenol in aquatic systems.
AB  - The sorption and desorption of 4-tert-octylphenol in aquatic systems were studied
      to unravel the underlying controls. The sorption process was relatively slow,
      reaching a final sorption equilibrium in 10 d. The sorption process was
      interpreted as consisting of two stages: an initial rapid adsorption on particle
      surface followed by a slow intraparticle diffusion. The key parameter affecting
      the sorption of 4-tert-octylphenol by sediment is the occurrence of colloids,
      which in turn explains the so-called sediment concentration (SC) effect. This was
      confirmed by the increasing amount of colloids with increasing SC, and the
      relative constancy of intrinsic partition coefficient of 4-tert-octylphenol
      between sediment and water (K(p)) and between colloids and water (K(c)). Further
      evidence was from the nonoccurrence of SC effect from the addition of the same
      amount of colloids in different SC. The adsorption equilibrium is best described
      by the Freundlich model at low equilibrium concentrations. The adsorption of 4
      tert-octylphenol was enhanced in the presence of salts, due to the salting out
      effect, and a salting constant of 1.3 L/mol was obtained. Desorption experiments
      showed that the release of 4-tert-octylphenol from contaminated sediments was
      highly dependent on the "age" of sediments, with kinetics of desorption being
      much faster in fresh sediments than in "aged" sediments.

PMID- 16646458
TI  - Sorption of Aldrich humic acid onto hematite: insights into fractionation
      phenomena by electrospray ionization with quadrupole time-of-flight mass
      spectrometry.
AB  - Sorption induced fractionation of purified Aldrich humic acid (PAHA) on hematite
      is studied through the modification of electrospray ionization (ESI) quadrupole
      time-of-flight (QToF) mass spectra of supernatants from retention experiments.
      The ESI mass spectra show an increase of the "mean molecular masses" of the
      molecules that constitutes humic aggregates. The low molecular weight fraction
      (LMWF; m/z < or = 600 Da) is preferentially sorbed compared to two other
      fractions. The resolution provided by ESI-QToF mass spectrometer in the low-mass
      range provided evidence of further fractionation induced by sorption within the
      LMWF. Among the two latter fractions, the high molecular weight fraction (HMWF;
      m/z approximately 1700 Da) seems to be more prone to sorption compared to the
      intermediate molecular weight fraction (IMWF; m/z approximately 900 Da). The IMWF
      seems to be more hydrophilic as it should be richer in O, N, and alkyl C from the
      proportion of even mass, and poorer in aromatic structures from mass defect
      analysis in ESI mass spectra.

PMID- 16646459
TI  - Atmospheric lifetime and global warming potential of a perfluoropolyether.
AB  - Perfluoropolyethers (PFPEs) are a family of perfluorinated fluids used mainly in
      industrial applications. Lower molecular weight commercial PFPE fractions have
      boiling points ranging between 55 and 270 degrees C, and have the potential to
      escape into the atmosphere. To improve our understanding of the atmospheric
      chemistry of PFPEs, a distilled fraction of a commercial mixture containing
      perfluoropolymethylisopropyl ethers (PFPMIEs) was introduced into an atmospheric
      chamber system. Relative rate techniques were used to determine upper limits for
      the rate constants for reactions of OH and Cl with PFPMIE in 700 Torr of air at
      296 K. The reactivity of PFPMIE with Cl was less than 2 x 10(-17) cm3 molecule(
      1) s(-1), while the reactivity with OH was less than 6.8 x 10(-16) cm3 molecule(
      1) s(-1), indicating low reactivity in the troposphere. Consequently, the
      lifetime of PFPMIE should be limited bytransport to the mesosphere, where
      photolysis by Lyman-alpha radiation at 121.6 nm will be efficient. By analogy to
      perfluorinated alkanes, the lower limit for the total atmospheric lifetime is 800
      years. PFPMIE was shown to have instantaneous radiative forcing of 0.65 W m(-2)
      ppb(-1), which corresponds to a global warming potential on a 100 year time scale
      of 9000 relative to CO2 and 1.95 relative to CFC-11.

PMID- 16646460
TI  - Formation and control of toxic polychlorinated compounds during incineration of
      wastes containing polychlorinated naphthalenes.
AB  - To estimate the potential impact on municipal solid waste (MSW) incinerator toxic
      equivalent (TEQ) emissions of treating wastes containing polychlorinated
      naphthalenes (PCNs), pilot-scale thermal treatment experiments were conducted.
      MSW (run 1) and MSW fortified with synthetic rubber belts containing PCNs (runs 2
      and 3) were incinerated. Flue-gas and ash samples were analyzed for
      polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), coplanar
      polychlorinated biphenyls (co-PCBs), and PCNs. Final exhaust-gas WHO-TEQ
      emissions were all less than 0.1 ng/Nm3. Flue-gas TEQs were mainly from PCDFs (58
      74%). When 2,3,7,8-tetrachlorodibenzo-p-dioxin relative potency factors (REPs) of
      specific PCN congeners from previous reports were used as estimated toxic
      equivalency factors to compute estimated PCN TEQs and total TEQs along with
      PCDDs, PCDFs, and co-PCBs, the contributions of PCNs to the total TEQs were small
      in ash samples and up to 28% in final exhaust gas. The TEQs in primary combustion
      flue gases increased through the formation of dioxins and PCNs and then decreased
      via secondary combustion, fabric filtration, and activated carbon adsorption.
      From this pilot-scale study, the incremental impact of incinerating PCN
      containing wastes on annual TEQ emissions in Japan is estimated as 0.27 g of
      total TEQ.

PMID- 16646461
TI  - Low frequency electrical properties of corroded iron barrier cores.
AB  - We investigated the electrical signatures of iron corrosion and mineral
      precipitation in angle cores from an Fe(0) barrier installation in operation for
      eight years. The real and imaginary parts of the complex electrical conductivity
      measured between 0.1 and 1000 Hz were 2-10 times higher (varying between cores)
      in the reacted zone at the upgradient edge of the barrier relative to less
      altered locations inside the barrier. Scanning electron microscopy identified
      iron surface alteration with the thickest corrosion rinds closest to the
      upgradient soil/iron interface. Surface area of iron minerals was also greatest
      at the upgradient interface, gradually decreasing into the cores. X-ray
      diffractometry identified precipitation of iron oxide/hydroxide, carbonate
      minerals, iron sulfide, as well as green rusts, with mineral complexity
      decreasing away from the interface. The electrical measurements correlate very
      well with the solid-phase analyses, and they verify that electrical methods could
      be used to assess or monitor iron corrosion and mineral precipitation occurring
      in Fe(0) barriers.

PMID- 16646462
TI  - Evidence of a stable uranyl site in ancient organic-rich calcite.
AB  - The mechanism of uranium (U) incorporation into calcite (calcium carbonate) is of
      fundamental importance to the fate and transport of U at the surface and in the
      shallow subsurface and has implications for (a) the accuracy of U-Pb and U-series
      isotope ratio methods used to determine the ages of ancient deposits and (b)
      potential remediation strategies based on sequestration of U in the subsurface.
      Extended X-ray absorption fine structure (EXAFS) spectroscopy is uniquely suited
      to the study of U-calcite systems. The sensitivity of the EXAFS spectrum to the
      local atomic Ca coordination about U(VI) in the calcite structure results in an
      increase in the number and amplitude of Ca signals as the U(VI) becomes more
      ordered within the crystal structure. Our X-ray microprobe (10-microm)
      measurements of an ancient 298 million-year-old organic-rich calcite (calcrete)
      clearly revealed three coordination shells of Ca atoms, defining a well-ordered
      calcite structure about uranyl to a distance of approximately 6.5 angstroms.
      These results indicate that uranyl is incorporated at the Ca2+ site in calcite
      and that the uranyl environment may evolve over long time scales, becoming more
      calcite-like and more stable for long-term sequestration of uranium. These
      results therefore validate U-related dating methods and show that calcite can be
      effective at sequestering U in vadose zone sediments.

PMID- 16646463
TI  - Culture-based MEMS device to track Gordonia in activated sludge.
AB  - Previously, we reported on the use of microelectromechanical systems (MEMS)
      fabrication technologies to develop paraffin surfaces for miniaturization of
      culture-based detection and rapid quantification of Mycolata in environmental
      samples. In the current study, the novel culture-based biochip was calibrated
      with a broad range of pure cultures of Mycolata including Gordonia spp. isolated
      from activated sludge foam. The biochip successfully recovered Gordonia amarae
      spiked into a sample of mixed liquor collected from a municipal activated sludge
      system. Comparisons of these results with molecular biology-based assays
      including 16S rRNA-targeted fluorescence in situ hybridization (FISH) and
      antibody staining demonstrated that the biochip provides a more rapid and user
      friendly platform for reliable identification and quantification of Mycolata in
      full-scale municipal activated sludge sewage treatment plants. The results of
      this work successfully demonstrate an alternative platform technology for
      inexpensive monitoring of environmental microorganisms using existing expertise
      by potential users in the area of bacterial cultivation.

PMID- 16646464
TI  - Spectroscopic investigation of Ni speciation in hardened cement paste.
AB  - Cement-based materials play an important role in multi-barrier concepts developed
      worldwide for the safe disposal of hazardous and radioactive wastes. Cement is
      used to condition and stabilize the waste materials and to construct the
      engineered barrier systems (container, backfill, and liner materials) of
      repositories for radioactive waste. In this study, Ni uptake by hardened cement
      paste has been investigated with the aim of improving our understanding of the
      immobilization process of heavy metals in cement on the molecular level. X-ray
      absorption spectroscopy (XAS) coupled with diffuse reflectance spectroscopy (DRS)
      techniques were used to determine the local environment of Ni in cement systems.
      The Ni-doped samples were prepared at two different water/cement ratios (0.4,
      1.3) and different hydration times (1 hour to 1 year) using a sulfate-resisting
      Portland cement. The metal loadings and the metal salts added to the system were
      varied (50 up to 5000 mg/kg; NO3(-), SO4(2-), Cl-). The XAS study showed that for
      all investigated systems Ni(ll) is predominantly immobilized in a layered double
      hydroxide (LDH) phase, which was corroborated by DRS measurements. Only a minor
      extent of Ni(ll) precipitates as Ni-hydroxides (alpha-Ni(OH)2 and beta-Ni(OH)2).
      This finding suggests that Ni-Al LDH, rather than Ni-hydroxides, is the
      solubility-limiting phase in the Ni-doped cement system.

PMID- 16646465
TI  - Contribution of first- versus second-generation products to secondary organic
      aerosols formed in the oxidation of biogenic hydrocarbons.
AB  - Biogenic hydrocarbons emitted by vegetation are important contributors to
      secondary organic aerosol (SOA), but the aerosol formation mechanisms are
      incompletely understood. In this study, the formation of aerosols and gas-phase
      products from the ozonolysis and photooxidation of a series of biogenic
      hydrocarbons (isoprene, 8 monoterpenes, 4 sesquiterpenes, and 3 oxygenated
      terpenes) are examined. By comparing aerosol growth (measured by Differential
      Mobility Analyzers, DMAs) and gas-phase concentrations (monitored by a Proton
      Transfer Reaction Mass Spectrometer, PTR-MS), we study the general mechanisms of
      SOA formation. Aerosol growth data are presented in terms of a "growth curve", a
      plot of aerosol mass formed versus the amount of hydrocarbon reacted. From the
      shapes of the growth curves, it is found that all the hydrocarbons studied can be
      classified into two groups based entirely on the number of double bonds of the
      hydrocarbon, regardless of the reaction systems (ozonolysis or photooxidation)
      and the types of hydrocarbons studied: compounds with only one double bond and
      compounds with more than one double bond. For compounds with only one double
      bond, the first oxidation step is rate-limiting, and aerosols are formed mainly
      from low volatility first-generation oxidation products; whereas for compounds
      with more than one double bond, the second oxidation step may also be rate
      limiting and second-generation products contribute substantially to SOA growth.
      This behavior is characterized by a vertical section in the growth curve, in
      which continued aerosol growth is observed even after all the parent hydrocarbon
      is consumed.

PMID- 16646466
TI  - Molecular simulations of benzene and PAH interactions with soot.
AB  - Molecular mechanics simulations and ab initio calculations were performed to
      investigate the mechanism of PAH-soot adsorption. Partitioning of benzene,
      naphthalene, fluorene, phenanthrene, anthracene, pyrene, fluoranthene,
      benzo[a]anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and
      benzo[g,h,i]perylene between water and soot was modeled with classical and
      quantum mechanical calculations in order to determine a method for predicting
      log(K(d)) values. In both cases, the predicted mechanism of adsorption is
      interaction of the pi-electrons in the PAH and soot (i.e., pi-pi van der Waals
      forces). Solvation energies, the energy difference between the solute in the gas
      phase and in the model aqueous phase, calculated with molecular mechanics did not
      follow the observed solubilities of the PAHs. Molecular dynamics simulations
      overestimate the favorability of PAHs in the aqueous phase. Hence, the
      partitioning between the aqueous phase and soot does not accurately correlate
      with observed log(K(d)) values. Models of PAH adsorption using structures from
      molecular mechanics and energies from ab initio calculations do produce water
      soot partitioning energies that correlate well with observed log(K(d)) values.
      The log(K(d)) values for benzene, anthracene, fluorene, and benzo[a]pyrene were
      predicted based on the correlation between calculated partitioning energies and
      observed log(K(d)) values. Results presented here suggest that partitioning of
      PAHs onto soot should depend on the size of the PAH, the planarity of PAH
      molecule, and the aromaticity of the compound. The methodology developed bythis
      research can be used to predict PAH K(d) values that have not yet been measured.

PMID- 16646467
TI  - Simulating the effect of aerobic biodegradation on soil vapor intrusion into
      buildings: influence of degradation rate, source concentration, and depth.
AB  - Steady-state vapor intrusion scenarios involving aerobically biodegradable
      chemicals are studied using a three-dimensional multicomponent numerical model.
      In these scenarios, sources of aerobically biodegradable chemical vapors are
      placed at depths of 1-14 m beneath a 10 m x 10 m basement or slab-on-grade
      construction building, and the simultaneous transport and reaction of hydrocarbon
      and oxygen vapors are simulated. The results are presented as Johnson and
      Ettinger attenuation factors alpha (predicted indoor air hydrocarbon
      concentration/source vapor concentration), and normalized contour plots of
      hydrocarbon and oxygen concentrations. In addition to varying the vapor source
      depth, the effects of source concentration (2-200 mg chemical/L vapor) and oxygen
      limited first-order reaction rates (0.018-1.8 h(-1)) are studied. Hydrocarbon
      inputs were specific to benzene, although the relevant properties are similar to
      those for a range of hydrocarbons of interest. Overall, the results suggest that
      aerobic biodegradation could play a significant role in reducing vapor intrusion
      into buildings (decreased alpha-values) relative to the no-biodegradation case,
      with the significance of aerobic biodegradation increasing with increasing vapor
      source depth, decreasing vapor source concentration, and increasing first-order
      biodegradation rate. In contrast to the no-biodegradation case, differences in
      foundation construction can be significant in some settings. The significance of
      aerobic biodegradation is directly related to the extent to which oxygen is
      capable of migrating beneath the foundation. For example, in the case of a
      basement scenario with a 200 mg/L vapor source located at 3 m bgs, oxygen is
      consumed before it can migrate beneath the foundation, so the attenuation factors
      for simulations with and without aerobic biodegradation are similar for all first
      order rates studied. For the case of a 2 mg/L vapor source located at 8 m bgs,
      the oxygen is widely distributed beneath the foundation, and the attenuation
      factor for the biodegradation case ranges from about 3 to 18 orders-of-magnitude
      less than that for the no-biodegradation case.

PMID- 16646468
TI  - Screening level risk assessment model for chemical fate and effects in the
      environment.
AB  - A screening level risk assessment model is developed and described to assess and
      prioritize chemicals by estimating environmental fate and transport,
      bioaccumulation, and exposure to humans and wildlife for a unit emission rate.
      The most sensitive risk endpoint is identified and a critical emission rate is
      then calculated as a result of that endpoint being reached. Finally, this
      estimated critical emission rate is compared with the estimated actual emission
      rate as a risk assessment factor. This "back-tracking" process avoids the use of
      highly uncertain emission rate data as model input. The application of the model
      is demonstrated in detail for three diverse chemicals and in less detail for a
      group of 70 chemicals drawn from the Canadian Domestic Substances List. The
      simple Level II and the more complex Level III fate calculations are used to
      "bin" substances into categories of similar probable risk. The essential role of
      the model is to synthesize information on chemical and environmental properties
      within a consistent mass balance framework to yield an overall estimate of
      screening level risk with respect to the defined endpoint. The approach may be
      useful to identify and prioritize those chemicals of commerce that are of
      greatest potential concern and require more comprehensive modeling and monitoring
      evaluations in actual regional environments and food webs.

PMID- 16646469
TI  - Use of Monte Carlo analysis to characterize nitrogen fluxes in agroecosystems.
AB  - Intensive agricultural systems are largely responsible for the increase in global
      reactive nitrogen compounds, which are associated with significant environmental
      impacts. The nitrogen cycle in agricultural systems is complex and highly
      variable, which complicates characterization in environmental assessments.
      Appropriately representing nitrogen inputs into an ecosystem is essential to
      better understand and predict environmental impacts, such as the extent of
      seasonally occurring hypoxic zones. Many impacts associated with reactive
      nitrogen are directly related to annual nitrogen loads, and are not adequately
      represented by average values that de-emphasize extreme years. To capture the
      inherent variability in agricultural systems, this paper employs Monte Carlo
      analysis (MCA) to model major nitrogen exports during crop production, focusing
      on corn-soybean rotations within the U.S. Corn Belt. This approach yields
      distributions of possible emission values and is the first step in incorporating
      variable nutrient fluxes into life cycle assessments (LCA) and environmental
      impact assessments. Monte Carlo simulations generate distributions of nitrate
      emissions showing that 80% of values range between 15 and 90 kg NO39-) N/ha (mean
      38.5 kg NO3(-) N/ha; median 35.7 kg NO3(-) N/ha) for corn fields and 5-60 kg NO3(
      ) N/ha (mean 20.8 kg NO3(-) N/ha; median 16.4 kg NO3(-) N/ha) for soybean fields.
      Data were also generated for grain and residue nitrogen, N2O, NO(x), and NH3.
      Results indicate model distributions are in agreement with available measured
      emissions.

PMID- 16646470
TI  - Secondary organic aerosol formation by heterogeneous reactions of aldehydes and
      ketones: a quantum mechanical study.
AB  - Experimental studies have provided convincing evidence that aerosol-phase
      heterogeneous chemical reactions (possibly acid-catalyzed) are involved to some
      extent in the formation of secondary organic aerosol (SOA). We present a stepwise
      procedure to determine physical properties such as heats of formation, standard
      entropies, Gibbs free energies of formation, and solvation energies from quantum
      mechanics (QM), for various short-chain aldehydes and ketones. We show that
      quantum mechanical gas-phase Gibbs free energies of formation compare reasonably
      well with the literature values with a root-mean-square (RMS) value of 1.83
      kcal/mol for the selected compounds. These QM results are then used to determine
      the equilibrium constants (reported as log K) of aerosol-phase chemical
      reactions, including hydration reactions and aldol condensation for formaldehyde,
      acetaldehyde, acetone, butanal, hexanal, and glyoxal. Results are in
      qualitatively agreement with previous studies. In addition, the QM results for
      glyoxal reactions are consistent with experimental observations. To our
      knowledge, this is the first QM study that supports observations of atmospheric
      particle-phase reactions. Despite the significant uncertainties in the absolute
      values from the QM calculations, the results are potentially useful in
      determining the relative thermodynamic tendency for atmospheric aerosol-phase
      reactions.

PMID- 16646471
TI  - Preliminary assessment of imidazolium-based room-temperature ionic liquids for
      extraction of organic contaminants from soils.
AB  - Alternative solvents known as room-temperature ionic liquids (RTILs) were
      considered for extraction of organic soil contaminants. A hydrophobic RTIL, 1
      butyl-3-methyl imidazolium hexafluorophosphate ([bmim]PF6), and a hydrophilic
      RTIL, 1-butyl-3-methyl imidazolium chloride ([bmim]Cl), were selected as
      representative imidazolium-based RTILs to assess the extraction of several
      organic contaminants (OCs) from two model soils. The two soils were
      montmorillonite (clay minerals, high surface area, and no organic matter) and
      glacial till (organic matter). The soils were spiked separately with DDT,
      dieldrin, hexachlorobenzene, and pentachlorophenol. With the exception of DDT,
      extractions of OCs from montmorillonite using [bmim]PF6 (79-92%) were nearly as
      effective as extractions with acetone and ethanol (85-100%). The extraction of
      OCs from glacial till with RTILs (15-61%) was less effective than extraction with
      organic solvents (59-100%). The [bmim]Cl was as efficient as [bmim]PF6 for
      extraction of OCs from glacial till, while [bmim]PF6 was more efficient than
      [bmim]Cl for extraction of OCs from montmorillonite. The two RTILs were most
      effective for the extraction of dieldrin (the heaviest OC) from both soils. The
      extraction results for glacial till showed dependence of OC extraction on the
      viscosity and melting point of RTILs.

PMID- 16646472
TI  - Development of a wet-chemical method for the speciation of iron in atmospheric
      aerosols.
AB  - The ability to quantify the chemical and physical forms of transition metals in
      atmospheric particulate matter (PM) is essential in determining potential human
      health and ecological effects. A method for the speciation of iron in atmospheric
      PM has been adapted which involves extraction in a well-defined solution followed
      by oxidation state specific detection. The method was applied to a suite of
      environmental aerosols. Ambient atmospheric aerosols in an urban area of St.
      Louis (the St. Louis-Midwest Supersite) were collected on Teflon substrates and
      were leached in one of four different solutions: (1) >18.0 Momega water; (2) 140
      microM NaCl solution; (3) pH = 7.4 NaHCO3 solution; and (4) pH = 4.3 acetate
      buffering system. Fe(ll) was determined directly using the Ferrozine method as
      adapted to liquid waveguide spectrophotometry using a 1 m path-length cell.
      Fe(lll) was determined similarly after reduction to Fe(ll). It was found that, at
      low ionic strength, pH exerted a major influence on Fe(ll) solubility with the
      greatest Fe(ll) concentration consistently found in the pH = 4.3 acetate buffer.
      Soluble Fe(lll) (as defined by a 0.2 microm filter) varied little with
      extractant, which implies that most of the Fe(lll) detected was colloidal. To
      characterize well-defined materials for future reference, NIST standard reference
      materials were also analyzed for soluble Fe(ll) and Fe(lll). For all SRMs tested,
      a maximum of 2.4% of the total iron (Urban Dust 1649a) was soluble in pH = 4.3
      acetate buffer. For calibration curves covering the ranges of 0.5-20 microg/L
      Fe(ll), excellent linearity was observed in all leaching solutions with R2 values
      of > 0.999. Co-located filters were used to test the effect of storage time on
      iron oxidation state in the ambient particles as a function of time. On two
      samples, an average Fe(ll) decay rate of 0.89 and 0.57 ng Fe(ll) g(-1) PM day(-1)
      was determined from the slope of the regression, however this decrease was
      determined not to be significant over 3 months (95% confidence). As an
      application of this method to mobile source emissions, size-resolved PM10 samples
      were collected at the inlet and outlet of the Caldecott Motor Vehicle Tunnel in
      northern California. These samples indicate that the coarse fraction (PM10-PM2.5)
      contains almost 50% of the total soluble Fe(ll) in the aerosol.

PMID- 16646473
TI  - Detection of deoxynivalenol in foods and indoor air using an array biosensor.
AB  - Deoxynivalenol (DON), a mycotoxin produced by several Fusaruim species, is a
      worldwide contaminant of foods and feeds. Because of the potential dangers due to
      accidental or intentional contamination of foods with DON, there is a need to
      develop a rapid and highly sensitive method for easy identification and
      quantification of DON. In this study, we have developed and utilized a
      competitive immunoassay technique to detect DON in various food matrixes and
      indoor air samples using an array biosensor. A DON-biotin conjugate, immobilized
      on a NeutrAvidin-coated optical waveguide, competed with the DON in the sample
      for binding to fluorescently labeled DON monoclonal antibodies. To demonstrate a
      simple procedure amenable for on-site use, DON-spiked cornmeal, cornflakes,
      wheat, barley, and oats were extracted with methanol-water (3:1) and assayed
      without cleanup or preconcentration. The limits of detection ranged from 0.2
      ng/mL in buffer to 50 ng/g in oats. The detection limit of DON spiked into an
      aqueous effluent from an air sampler was 4 ng/mL.

PMID- 16646474
TI  - Optimized parameters for fluorescence-based verification of ballast water
      exchange by ships.
AB  - Mid-ocean ballast water exchange is mandatory for ships discharging foreign
      ballast in US territorial waters in order to reduce the risk of biological
      invasions. However, a reliable tool for determining whether the procedure took
      place is lacking. We investigated chromophoric dissolved organic matter (CDOM)
      fluorescence as a tracer of mid-ocean exchange on nine research cruises out of
      Asia, Europe, and the USA, focusing on challenging source conditions (high
      salinity, low CDOM). Using parallel factor analysis, we identified nine
      independent fluorescent components present in varying concentrations in the ocean
      and in ballast water. One component was sufficient for predicting the coastal vs
      oceanic source of most ballast water samples. Across nine cruises, thresholds
      (1.7 and 0.7 ppb quinine sulfate equivalent units) at two fixed wavelength pairs
      (lambda(ex)/lambda(em) = 320/414 and 370/496 nm, respectively) discriminated
      coastal from oceanic ballast water in > 95% of samples (N = 514). Our results
      suggest that single- and dual-channel fluorometers could be optimized for
      verifying ballast water exchange.

PMID- 16646475
TI  - Development of chemical oxygen demand on-line monitoring system based on a
      photoelectrochemical degradation principle.
AB  - A simple, rapid, and sensitive on-line chemical oxygen demand (COD) determination
      method has been proposed and experimentally validated. The method is based on a
      photoelectrochemical oxidative degradation principle and operates under a
      continuous flow mode. The method employs a specially designed thin-layer
      photoelectrochemical cell that incorporates a highly effective nanoparticulate
      TiO2 photoanode. This approach overcomes many problems associated with the
      conventional COD determination techniques such as long analysis time, consumption
      of expensive and toxic reagents, production of secondary toxic waste, and poor
      reproducibility. The effect of important experimental parameters on the
      analytical signal generation was systematically investigated, and the optimum
      conditions were obtained. The method was successfully applied to determine the
      COD of real samples from various industrial wastewaters. The COD value of real
      samples determined by this method agreed well with the standard dichromate
      method. The assay time of 1-5 min/sample can be readily achieved. A practical
      detection limit of 1 mg L(-1) COD with a linear range of 1-100 mg L(-1) was
      achieved under the optimum conditions.

PMID- 16646476
TI  - ZrO2-modified mesoporous nanocrystalline TiO2-xNx as efficient visible light
      photocatalysts.
AB  - Mesoporous nanocrystalline TiO2-xNx and TiO2-xNx/ZrO2 visible-light
      photocatalysts have been prepared by a sol-gel method. The photocatalysts were
      characterized by XRD, N2 adsorption-desorption, TEM, XPS, UV/Vis, and IR
      spectroscopy. The photocatalytic activity of the samples was evaluated by the
      decomposition of ethylene in air under visible light (lambda > 450 nm)
      illumination. Results revealed that nitrogen was doped into the lattice of TiO2
      by the thermal treatment of NH3-adsorbed TiO2 hydrous gels, converting the TiO2
      into a visible-light responsive catalyst. The introduction of ZrO2 into TiO2-xNx
      considerably inhibits the undesirable crystal growth during calcination.
      Consequently, the ZrO2-modified TiO2-xNx displays higher porosity, higher
      specific surface area, and an improved thermal stability over the corresponding
      unmodified TiO2-xNx samples.

PMID- 16646477
TI  - Particle emissions from diesel passenger cars equipped with a particle trap in
      comparison to other technologies.
AB  - Tail pipe particle emissions of passenger cars, with different engine and
      aftertreatment technologies, were determined with special focus on diesel engines
      equipped with a particle filter. The particle number measurements were performed,
      during transient tests, using a condensation particle counter. The measurement
      procedure complied with the draft Swiss ordinance, which is based on the findings
      of the UN/ECE particulate measurement program. In addition, particle mass
      emissions were measured by the legislated and a modified filter method. The
      results demonstrate the high efficiency of diesel particle filters (DPFs) in
      curtailing nonvolatile particle emissions over the entire size range. Higher
      emissions were observed during short periods of DPF regeneration and immediately
      afterward, when a soot cake has not yet formed on the filter surface. The
      gasoline vehicles exhibited higher emissions than the DPF equipped diesel
      vehicles but with a large variation depending on the technology and driving
      conditions. Although particle measurements were carried out during DPF
      regeneration, it was impossible to quantify their contribution to the overall
      emissions, due to the wide variation in intensity and frequency of regeneration.
      The numbers counting method demonstrated its clear superiority in sensitivity to
      the mass measurement. The results strongly suggest the application of the
      particle number counting to quantify future low tailpipe emissions.

PMID- 16646478
TI  - Remediation of elemental mercury using in situ thermal desorption (ISTD).
AB  - In situ thermal desorption (ISTD) is a soil heating method that simultaneously
      applies heat and vacuum to the subsurface at temperatures up to 600 degrees C. As
      the soil is heated, the vapor pressure of the contaminant increases allowing mass
      transfer to the gas phase and extraction from the soil using vacuum wells. The
      overall goal of this research is to assess the feasibility of using ISTD to
      remove elemental mercury from soils. The initial phase of research included
      design of a laboratory soil column apparatus and preliminary soil column
      experiments with surrogate nonaqueous phase liquids (perfluorocarbons) to test
      the apparatus and investigate the effects of air flow rate and temperature on the
      ISTD process. Following the preliminary experiments, a mercury off-gas treatment
      system was added and mercury experiments were conducted. Experiments performed
      using elemental mercury showed greater than 99.8% removal of the mercury from
      Ottawa sand. These results show that ISTD can remove mercury from soil at
      temperatures well below its boiling point and that perfluorodecalin can be used
      as a surrogate for elemental mercury in laboratory experiments. A flow and
      transport simulator was used to model the results from both the perfluorocarbon
      and the mercury experiments.

PMID- 16646479
TI  - Gaseous hexane biodegradation by Fusarium solani in two liquid phase packed-bed
      and stirred-tank bioreactors.
AB  - Biofiltration of hydrophobic volatile pollutants is intrinsically limited by poor
      transfer of the pollutants from the gaseous to the liquid biotic phase, where
      biodegradation occurs. This study was conducted to evaluate the potential of
      silicone oil for enhancing the transport and subsequent biodegradation of hexane
      by the fungus Fusarium solani in various bioreactor configurations. Silicone oil
      was first selected among various solvents for its biocompatibility,
      nonbiodegradability, and good partitioning properties toward hexane. In batch
      tests, the use of silicone oil improved hexane specific biodegradation by
      approximately 60%. Subsequent biodegradation experiments were conducted in
      stirred-tank (1.5 L) and packed-bed (2.5 L) bioreactors fed with a constant
      gaseous hexane load of 180 g x m(-3)(reactor) x h(-1) and operated for 12 and 40
      days, respectively. In the stirred reactors, the maximum hexane elimination
      capacity (EC) increased from 50 g x m(-3)(reactor) x h(-1) (removal efficiency,
      RE of 28%) in the control not supplied with silicone oil to 120 g x m(
      3)(reactor) x h(-1) in the biphasic system (67% RE). In the packed-bed
      bioreactors, the maximum EC ranged from 110 (50% RE) to 180 g x m(-3)(reactor) x
      h(-1) (> 90% RE) in the control and two-liquid-phase systems, respectively. These
      results represent, to the best of our knowledge, the first reported case of fungi
      use in a two-liquid-phase bioreactor and the highest hexane removal capacities so
      far reported in biofilters.

PMID- 16646480
TI  - Biodegradation of p-nitrophenol by aerobic granules in a sequencing batch
      reactor.
AB  - In this study, aerobic granules to treat wastewater containing p-nitrophenol
      (PNP) were successfully developed in a sequencing batch reactor (SBR) using
      activated sludge as inoculum. A key step was the conditioning of the activated
      sludge seed to enrich for biomass with improved settleability and higher PNP
      degradation activity by implementing progressive decreases in settling time and
      stepwise increases in PNP concentration. The aerobic granules were cultivated at
      a PNP loading rate of 0.6 kg/ m3 x day, with glucose to boost the growth of PNP
      degrading biomass. The granules had a clearly defined shape and appearance,
      settled significantly faster than activated sludge, and were capable of nearly
      complete PNP removal. The granules had specific PNP degradation rates that
      increased with PNP concentration from 0 to 40.1 mg of PNP/L, peaked at 19.3 mg of
      PNP/(g of VSS) x h (VSS = volatile suspended solids), and declined with further
      increases in PNP concentration as substrate inhibition effects became
      significant. Batch incubation experiments show that the PNP-degrading granules
      could also degrade other phenolic compounds, such as hydroquinone, p
      nitrocatechol, phenol, 2,4-dichlorophenol, and 2,6-dichlorophenol. The PNP
      degrading granules contained diverse microbial morphotypes, and PNP-degrading
      bacteria accounted for 49% of the total culturable heterotrophic bacteria.
      Denaturing gradient gel electrophoresis analysis of 16S rRNA gene fragments
      showed a gradual temporal shift in microbial community succession as the granules
      developed from the activated sludge seed. Specific oxygen utilization rates at
      100 mg/L PNP were found to increase with the evolution of smaller granules to
      large granules, suggesting that the granulation process can enhance metabolic
      efficiency toward biodegradation of PNP. The results in this study demonstrate
      that it is possible to use aerobic granules for PNP biodegradation and broadens
      the benefits of using the SBR to target treatment of toxic and recalcitrant
      organic compounds.

PMID- 16646481
TI  - Reducing 1,3-dichloropropene emissions from soil columns amended with thiourea.
AB  - Soil fumigants are becoming an important source of volatile organic compounds
      (VOCs) in air, especially in some agricultural areas. In this study, we used
      thiourea to construct a reactive surface barrier (RSB) at the soil surface for
      reducing 1,3-dichloropropene (1,3-D) volatilization. The agrochemical thiourea
      could rapidly transform volatile 1,3-D to nonvolatile products via an SN2
      nucleophilic substitution reaction. A catalytic mechanism in thiourea-amended
      soil facilitated the conversion process. A packed soil column system was employed
      to investigate the emissions and distribution of 1,3-D and optimize the original
      fumigant emission-reduction strategy. Volatilization of 1,3-D from the soil
      surface was significantly reduced in columns amended with a thiourea RSB compared
      with that of bare soil. Volatilization flux and cumulative emissions decreased
      with increasing thiourea application rate and increasing fumigation depth in
      packed soil columns. Surface amendment with the RSB did not affect the subsurface
      distribution of 1,3-D in the soil profile. Combined application of a thiourea RSB
      and plastic tarps had a synergetic effect in emission control and could eliminate
      the relatively high fumigant flux that occurs upon tarp disruption. Therefore,
      this reduced-risk practice was very effective in reducing atmospheric emissions
      of VOCs from soil treatment with halogenated fumigants.

PMID- 16646482
TI  - Performance of forward (direct) osmosis process: membrane structure and transport
      phenomenon.
AB  - The performance of a forward (direct) osmosis (FO) process was investigated using
      a laboratory-scale unit to elucidate the effect of membrane structure and
      orientation on waterflux. Two types of RO membrane and a FO membrane were tested
      using ammonium bicarbonate, glucose, and fructose as the draw solution to extract
      water from a saline feed solution. The FO membrane was able to achieve higher
      water flux than the RO membranes under the same experimental conditions while
      maintaining high salt rejection of greater than 97%. Increasing operating
      temperature increased the water flux in FO process. To investigate the effect of
      membrane orientation on water flux, the FO membrane was tested normally (dense
      selective layer facing draw solution) and reversely (dense selective layer facing
      feed solution). Explanations on transport phenomenon in FO process were proposed
      which explain the observation that the FO membrane, when used in the normal
      orientation, performed better due to lesser internal concentration polarization.
      This study suggests that an ideal FO membrane should consist of a thin dense
      selective layer without any loose fabric support layer.

PMID- 16646483
TI  - Electrodialysis for recovering salts from a urine solution containing
      micropollutants.
AB  - Electrodialysis was investigated for the separation of micropollutants from
      nutrients in anthropogenic urine. In a continuously operated process, the
      nutrients were concentrated up to a factor of 3.2. The concentration factor was
      limited by water transport across the membrane. Water transport was caused by
      osmosis and electroosmosis, and a model was developed to describe these
      phenomena. The removal of several spiked micropollutants was investigated in
      continuous electrodialysis experiments. Ethinylestradiol was removed completely
      during the whole operating period. Diclofenac and carbamazepine were initially
      retained, but limited permeation (5-10%) occurred after longer operating times
      (90 days). Retentions of propranolol and ibuprofen were also high initially, but
      substantial breakthroughs occurred during extended operation. Considerable
      adsorption on the membranes was observed for all compounds. The permeation
      mechanism of several compounds appears to depend on the adsorbed amount on the
      membrane, which indicates that partitioning and diffusion mechanisms play an
      important role in the permeation transport. Partial desorption occurred in
      leaching experiments with polarity reversal, and almost quantitative desorption
      was observed after incubation of the membranes with Filter Count Gel Solution.
      Because environmental concentrations are much lower than the concentrations
      spiked here, it can be anticipated that operation without significant permeation
      is possible in practice during extended periods of time.

PMID- 16646484
TI  - Photosensitized destruction of Chlorella vulgaris by Methylene Blue or Nuclear
      Fast Red combined with hydrogen peroxide under visible light irradiation.
AB  - A considerable number of investigations have started to elucidate the essential
      roles biological agents play in the biodeterioration of stone. Chemical biocides
      are becoming increasingly banned because of the environmental and health hazards
      associated with these toxic substances. The present study reports the
      photodynamic effect of Methylene Blue (MB) and Nuclear Fast Red (NFR) in the
      presence of hydrogen peroxide (H2O2) on the destruction of the algae Chlorella
      vulgaris (C. vulgaris) under irradiation with visible light. Illumination of C.
      vulgaris in the presence of MB or NFR combined with H2O2 results in the
      decomposition of both the algal species and the photosensitizer. The photodynamic
      effect was investigated under aerobic and anaerobic conditions. Differences in
      mechanism type are reported and are dependent on both the presence and the
      absence of oxygen. The behavior of each photosensitizer leads to a Type II
      mechanism and a Type I/Type II combination for MB and NFR, respectively, being
      concluded. This novel combination could be effective for the remediation of
      biofilm-colonized stone surfaces.

PMID- 16646485
TI  - Increased power generation in a continuous flow MFC with advective flow through
      the porous anode and reduced electrode spacing.
AB  - The maximum power generated in a single-chamber air-cathode microbial fuel cell
      (MFC) has previously been shown to increase when the spacing between the
      electrodes is decreased from 4 to 2 cm. However, the maximum power from a MFC
      with glucose (500 mg/L) decreased from 811 mW/ m2 (R(ex) = 200 omega, Coulombic
      efficiency of CE = 28%) to 423 mW/m2 (R(ex) = 500 omega, CE = 18%) when the
      electrode spacing was decreased from 2 to 1 cm (batch mode operation, power
      normalized by cathode projected area). This decrease in power was unexpected as
      the internal resistance decreased from 35 omega (2-cm spacing) to 16 omega (1-cm
      spacing). However, providing advective flow through the porous anode toward the
      cathode substantially increased power, resulting in the highest maximum power
      densities yet achieved in an air-cathode system using glucose or domestic
      wastewater as substrates. For glucose, with a 1-cm electrode spacing and flow
      through the anode with continuous flow operation of the MFC, the maximum power
      increased to 1540 mW/m2 (51 W/m3) and the CE increased to 60%. Using domestic
      wastewater (255 +/- 10 mg of COD/L), the maximum power density was 464 mW/m2
      (15.5 W/m3; CE = 27%). Although flow through the anode could lead to plugging,
      especially for particulate substrates such as domestic wastewater, the system was
      operated using glucose for over 42 days without clogging. These results show that
      power output in this air-cathode single-chamber MFC can be increased by reducing
      the electrode spacing if the reactors are operated in continuous flow mode with
      advective flow through the anode toward the cathode.

PMID- 16646486
TI  - Process-based control of HAPs emissions from drying wood flakes.
AB  - Industrial wood flake drying generates methanol, formaldehyde, and other
      hazardous air pollutants (HAPs). A simple theoretical model shows that particles
      smaller than 400 microm will begin to thermally degrade and release
      disproportionately large quantities of HAPs. This is confirmed in full-scale
      practice where particles smaller than 500 microm show visible signs of charring.
      Laboratory measurement of the activation energy for the breakdown of wood tissue
      into methanol and formaldehyde led to a value of about 17 kcal/mol. The apparent
      activation energy measured in the field was higher. This result was obtained
      under nonisothermal conditions and is biased high by the fines fraction of the
      furnish, which is exposed to elevated temperatures. It is proposed that a
      combination of screening out the fines fraction smaller than 500 microm and
      reducing the dryer inlet temperature will substantially reduce emissions,
      possibly to the point where control devices can be downsized or eliminated. Our
      findings allow these HAPs reductions to be semiquantitatively estimated.

PMID- 16646487
TI  - Effects of a complex mixture of therapeutic drugs at environmental levels on
      human embryonic cells.
AB  - The potential risk associated with the presence of low levels of pharmaceuticals
      in aquatic environments is currently under debate. In this study we investigated
      the effects of 13 drugs merged to mimic both the association and low
      concentration (ng/L) profiles detected in the environment. The mixture comprised
      atenolol, bezafibrate, carbamazepine, cyclophosphamide, ciprofloxacin,
      furosemide, hydrochlorothiazide, ibuprofen, lincomycin, ofloxacin, ranitidine,
      salbutamol, and sulfamethoxazole. At environmental exposure levels, the drug mix
      inhibited the growth of human embryonic cells HEK293, with the highest effect
      observed as a 30% decrease in cell proliferation compared to controls.
      Pharmaceuticals activated stress-response signaling protein kinases (ERK1/2), and
      induced overexpression of glutathione-S-transferase P1 gene. No evidence was
      found for apoptosis or necrosis in HEK293 cells, although morphological changes
      were observed. The drug mixture effectively stimulated the expression of cell
      cycle progression-mediating genes p16 and p21, with a slight accumulation of
      cells in the G2/M phase of the cell-cycle. Our results suggest that a mixture of
      drugs at ng/L levels can inhibit cells proliferation by affecting their
      physiology and morphology. This also suggests that water-borne pharmaceuticals
      can be potential effectors on aquatic life.

PMID- 16646488
TI  - New risk assessment approach for systemic insecticides: the case of honey bees
      and imidacloprid (Gaucho).
AB  - The procedure to assess the risk posed by systemic insecticides to honey bees
      follows the European Directives and depends on the determination of the Hazard
      Quotient (HQ), though this parameter is not adapted to these molecules. This
      paper describes a new approach to assess more specifically the risk posed by
      systemic insecticides to honey bees with the example of imidacloprid (Gaucho).
      This approach is based on the new and existing chemical substances Directive in
      which levels of exposure (PEC, Predicted Exposure Concentration) and toxicity
      (PNEC, Predicted No Effect Concentration) are compared. PECs are determined for
      different categories of honey bees in relation to the amounts of contaminated
      pollen and nectar they might consume. PNECs are calculated from data on acute,
      chronic, and sublethal toxicities of imidacloprid to honey bees, to which
      selected assessment factors are applied. Results highlight a risk for all
      categories of honey bees, in particular for hive bees. These data are discussed
      in the light of field observations made on honey bee mortalities and
      disappearances. New perspectives are given to better determine the risk posed by
      systemic insecticides to honey bees.

PMID- 16646489
TI  - Biological validation of a sample preparation method for ER-CALUX bioanalysis of
      estrogenic activity in sediment using mixtures of xeno-estrogens.
AB  - The combined estrogenic effects of mixtures of environmental pollutants in the in
      vitro ER-CALUX (chemical activated luciferase gene expression) bioassaywere
      examined to biologically validate a sample preparation method for the analysis of
      estrogenic compounds in sediment. The method used accelerated solvent extraction
      (ASE) and gel permeation chromatography (GPC) and was validated with respect to
      recovery of biological response taking mixture effects into account. Four
      mixtures of three to six xenoestrogenic compounds (bisphenol A, 4-nonylphenol,
      (4,4'-dichlorodiphenyl)trichloroethane, (2,4'-dichlorodiphenyl)trichloroethane,
      dieldrin, 4-n-octylphenol, alpha-chlordane, dibutylphthalate, (4,4'
      dichlorodiphenyl)dichloroethylene, and 2,4,5-trichlorobiphenyl) were prepared.
      Experimentally determined mixture effects were well described by the concept of
      concentration addition (CA), as expected for similarly acting compounds. Observed
      estradiol equivalence factors of the mixtures (on average 1.2 +/- 0.3) agreed
      very well with the value predicted according to CA. The sample preparation method
      was then applied to pure mixtures of standards and to sediment spiked with one of
      the mixtures. Recoveries of estrogenic compounds were estimated by determination
      of their mixture potencies in ER-CALUX and compared to the mixture effects
      predicted by CA. Recoveries of estrogenic activity were between 80 and 129%,
      indicating that the additive behavior of mixtures of xeno-estrogens is well
      conserved during sample preparation. Together with an average repeatability of
      18.3%, low average limit of detection (2.6 +/- 1.8 pg of EEQ/ g), and coefficient
      of variance (3.5 +/- 3.3%),this demonstrated the suitability of the sample
      preparation method for the analysis of mixtures of (xeno-)estrogenic compounds in
      sediment with the ER-CALUX assay.

PMID- 16646490
TI  - Biomimetic approach to biomembrane models studies: medium influence on the
      interaction kinetics of some phenylurea derivatives herbicides.
AB  - The ability of herbicides to interact with cell membranes outer lipid layer and
      subsequently to penetrate inside cells can be a prerequisite for exhibiting a
      toxic activity for both the directly exposed workers and the end consumers as the
      herbicides are present in the soil and water. The effect exerted by fenuron,
      chlorotoluron, metobromuron, monolinuron, and chlorbromuron, five structurally
      similar phenylurea herbicides, on the thermotropic behavior of model membranes,
      represented by dimyristoylphosphatidylcholine (DMPC) vesicles, was investigated
      by differential scanning calorimetry. The examined compounds, when dispersed in
      liposomes during their preparation, exerted a different action on the gel-to
      liquid crystal phase transition of DMPC multilamellar vesicles. The ability of
      phenylurea herbicides, as a finely powdered solid, to migrate through an aqueous
      medium and interact with biomembrane models was also studied. This transfer
      process was compared with these compounds intermembrane transfer from herbicide
      loaded liposomes to empty ones. These processes can mimic absorption kinetics
      mediated by hydrophilic or lipophilic media. Different rate and entity of
      interaction occurred between model membranes and solid phenylurea herbicides.
      Different behavior was observed by considering the time-dependent studies carried
      out by contacting, for increasing times, equivalent amounts of empty DMPC
      vesicles with phenylurea herbicide-loaded ones; all compounds were able to
      migrate from loaded to empty DMPC vesicles. Thus, phenylurea herbicides are able
      to reach and penetrate biological membranes when dispersed in a lipophilic or
      hydrophilic medium; these processes are related to the substituents present on
      the compounds backbone. The obtained experimental results seem to validate the
      employed strategy to study the ability of bioactive compounds to both interact
      with biological membranes and be adsorbed inside a membrane mimicking a
      biological cell when dispersed in a lipophilic or hydrophilic medium.

PMID- 16646491
TI  - Biomonitoring human exposure to organohalogenated substances by measuring urinary
      chlorophenols using a high-throughput screening (HTS) immunochemical method.
AB  - The widespread contamination of the environment by persistent organochlorinated
      substances is well-known. High-throughput immunochemical methods may improve
      routine assessment of the exposure of the population to these chemicals by
      analyzing urinary biomarkers. Trichlorophenols (TCP) have often been considered
      as biomarkers of many organochlorinated compounds. With the aim to assess
      exposure of the population to these substances a high-throughput immunosorbent
      solid-phase extraction (HTS-IS-SPE) procedure coupled to ELISA for simultaneous
      analyses of 2,4,6-TCP immunoreactivity equivalents (2,4,6-TCP-IR equiv) in
      multiple hydrolyzed urine samples has been developed. Around 100 urine samples
      can be processed simultaneously with an inter- and intraassay precision lower
      than 23% CV and a limit of detection of 0.3 microg L(-1). The analyses by HTS-IS
      SPE-ELISA and HTS-IS-SPE-GC/MS of urine samples (N = 117) collected from three
      different population groups point to a broad exposure of the Catalonian
      population to organohalogenated substances including the recently emerging
      organobrominated pollutants. Environment and edible products seem to be the most
      likely sources of exposure, since excretion of 2,4,6-TCP-IR equiv has been found
      to be independent from the occupational sector. An excellent correlation was
      observed between the 2,4,6-TCP-IR equiv determined by HTS-IS-SPE-ELISA and the
      concentrations measured by HTS-IS-SPE-GC/MS (R2 = 0.912). The results show that
      immunochemical screening methods, based on the quantification of urinary
      biomarkers, can be excellent tools for exposure assessment. The HTS-IS-SPE-ELISA
      presented here has proved to be efficient, precise, accurate, rapid, and
      specific, which opens up the possibility for a broad variety of applications
      where routine testing of large number of samples is required.

PMID- 16646492
TI  - Temporal dynamics of effect concentrations.
AB  - In effect assessment the comparability and applicability of LCx and ECx values,
      which are calculated at single points in time during exposure, relies on the
      ability to perform a valid extrapolation to other time points of interest. The
      behavior of LCx in time has been extensively studied, and the behavior of ECx in
      time is expected to follow similar dynamics, as it is considered that the LCx is
      just a specific case of ECxs. However, most models have focused on validating the
      dynamics of LCx, and hardly anything is known about the time dependence of ECx
      for other endpoints or whether it is comparable to that of LCxs. We have created
      four scenarios where we study the dynamics of the ECx for different endpoints and
      how it is affected by the characteristics of two different compounds (carbendazim
      and pentachlorobenzene) and of two different life history strategies
      (hermaphroditic and sexually reproducing strains of Caenorhabditis elegans). The
      observed patterns of behavior in time of the ECx for body size and for
      reproduction showed unexpected dynamics that deviate considerably from that of
      the LCx. It was demonstrated that the temporal dynamics of ECx were very
      different for each particular endpoint. The shape of the ECx-time curves depends
      on the intrinsic characteristics of the endpoint of study, as well as on the
      characteristics of the compound and life history strategy of the organism. This
      makes extrapolation in time or between endpoints difficult and hampers the
      comparability of results based on this summary statistic. The interpretation of
      the results from toxicity tests can be improved through process-based modeling,
      as demonstrated on the current data set.

PMID- 16646493
TI  - Comment on "In-stream nitrogen attenuation: model-aggregation effects and
      implications for coastal nitrogen impacts".

PMID- 16646494
TI  - Comment on "Sorption kinetics of organic contaminants by sandy aquifer and its
      kerogen isolate".

PMID- 16646495
TI  - Comment on "Biodegradation of alpha-pinene in model biofilms in biofilters".

PMID- 16646496
TI  - Forms and functions of family mealtimes: multidisciplinary perspectives.

PMID- 16646497
TI  - "Everyone would be around the table": American family mealtimes in historical
      perspective, 1850-1960.

PMID- 16646498
TI  - The cultural structuring of mealtime socialization.

PMID- 16646499
TI  - Mealtime talk that supports literacy development.

PMID- 16646500
TI  - Routine and ritual elements in family mealtimes: contexts for child well-being
      and family identity.

PMID- 16646501
TI  - Eating among teens: do family mealtimes make a difference for adolescents'
      nutrition?

PMID- 16646502
TI  - Veneer prep opinions.

PMID- 16646503
TI  - Under our watch.

PMID- 16646504
TI  - Snap-on smile: two case studies.

PMID- 16646505
TI  - Research indicates "bridge in the gap" between oral and systemic health.

PMID- 16646506
TI  - Dynamite diagnosis...empowered performance.

PMID- 16646507
TI  - The use of osteotomes in dental implant surgery.

PMID- 16646508
TI  - Fabrication of an overdenture covering a torus palatinus using a combination of
      denture base materials: a case report.
AB  - A maxillary torus provides a challenge when restoring an edentulous arch. Tori
      tend to have very thin mucosa and can be intolerant of normal pressures from a
      denture base. The tori tend to have large undercuts and at times extend to the
      junction with the soft palate, preventing the creation of a good palatal seal.
      Triple lamination involves combining 3 materials to fabricate a denture base that
      utilizes the retentive aspects of the torus. The thermoplastic flange provides a
      measure of flexibility, allowing the denture to seat over the torus. The
      resilient liner provides a cushion to diffuse the occlusal load, while the rigid
      acrylic base provides the support for the denture teeth. Using this approach, a
      very retentive denture was fabricated using the maxillary torus as a key element
      in anchoring the prosthesis.

PMID- 16646509
TI  - A systematic approach to dento-facial smile evaluation using digital photography
      and a new photographic view.

PMID- 16646510
TI  - Minimally invasive porcelain repair using high-strength, wrapped aesthetic
      veneers.

PMID- 16646511
TI  - Laser resource and reference guide.

PMID- 16646512
TI  - Assuaging postoperative effects of periodontal surgery.
AB  - Responding to the patient's uncomfortable reaction following certain periodontal
      surgery procedures, notably the sensitivity to temperature and touch, has been a
      source of frustration to both the practitioner performing the surgery as well as
      the patient. This case demonstrates the placement of an easily applied
      desensitizing paste (Duraphat) at the time of surgery, which enables the patient
      to avoid uncomfortable sensitivity after the dressing has been removed and allows
      the patient to return to good oral hygiene practices quickly, thereby avoiding
      new accumulation of bacteria. It also prevents further periodontal destruction,
      which is the purpose of the periodontal treatment. This presentation and
      diagrammatic explanation demonstrate placing this topical paste during the
      surgery, just before suturing. This particular paste is easy to place, and ease
      of placement is not inhibited by moisture in the affected area. The desensitizing
      effect for the immediate postoperative period provides comfort for the patient
      and helps to maintain trust between the dentist and the patient.

PMID- 16646513
TI  - Combining radiosurgery and Captek restorations: case reports.

PMID- 16646514
TI  - Full-mouth reconstuction with veneers and restorations: case report.

PMID- 16646515
TI  - Treating dental patients with eating disorders.

PMID- 16646516
TI  - Fixing a broken bonus system: the Triple-Win Approach.

PMID- 16646517
TI  - How to integrate computer technology into the practice: maximizing your
      investment.

PMID- 16646518
TI  - Tooth flattening: a simple technique for consistent endodontic access.

PMID- 16646519
TI  - Shaping for success...everything old is new again.

PMID- 16646520
TI  - Vasopressin and nitric oxide synthesis after three days of water or food
      deprivation.
AB  - Nitric oxide has been suggested to be involved in the regulation of fluid and
      nutrient homeostasis. In the present investigation, vasopressin and nitric oxide
      metabolite (nitrite and nitrate) levels were determined in plasma of male Wistar
      rats submitted to water or food deprivation for three days. Hematocrit and plasma
      sodium showed marked increase in dehydrated and starved rats. Potassium levels
      and plasma volume decreased in both treated groups. Plasma osmolality and
      vasopressin levels were significantly elevated in water deprived (362.8 +/- 7.1
      mOsm/kg H2O, 17.3 +/- 2.7 pg/ml, respectively, p < 0.001) rats, but not in food
      deprived (339.9 +/- 5.0, 1.34 +/- 0.28) rats, compared to the controls (326.1 +/-
      4.1, 1.47 +/- 0.32). The alterations observed in plasma vasopressin levels were
      related to plasma osmolality rather than plasma volume. Plasma levels of nitrite
      and nitrate were markedly increased in both water and food deprived rats
      (respectively, 2.19 +/- 0.29 mg/l and 2.22 +/- 0.17 mg/l versus 1.33 +/- 0.19
      mg/l, both p < 0.01). There was a significant negative correlation between plasma
      nitrite and nitrate concentration and plasma volume. These results suggest that
      both dehydration and starvation increase plasma nitric oxide, probably by
      activation of nitric oxide synthases. The release of nitric oxide may participate
      in the regulation of the alteration in blood flow, fluid and nutrient metabolism
      caused by water deprivation or starvation.

PMID- 16646521
TI  - Effect of testosterone loading on the kinetic of faecal testosterone excretion in
      mallards.
AB  - Intestinal passage time of coloured fodder and testosterone turnover were
      examined by faecal steroid analysis in mallards in the reproductive and
      postrefractory period. In the latter, the discharge of coloured fodder began 36
      minutes after ingestion in males, and 56 minutes in females. During reproduction
      the discharge began 93 minutes and 112 minutes after ingestion in males and
      females, respectively. Total passage time was similar in the reproductive and
      postrefractory period in both sexes. After intraperitoneal testosterone
      injection, faecal samples were collected for 8 hours and testosterone levels were
      measured using RIA. In the postrefractory period, 1-2 hours after testosterone
      loading a strong increase of faecal testosterone content developed in males,
      meanwhile a slighter testosterone peak appeared in females. During reproduction
      testosterone excretion began 1.5-2 hours after injection in both sexes but in
      females its increase was smaller. The duration of response to testosterone
      loading was 5 hours in both periods and both sexes. Intensive excretion after T
      loading appeared earlier in males than in females, but total passage time
      finished at the same time: 5 hours after loading. The character of testosterone
      excretion was corresponding to the passage of fodder-chimus-faeces in the
      reproductive and postrefractory period in both sexes.

PMID- 16646522
TI  - Effects of aqueous extract of Alpinia calcarata rhizomes on reproductive
      competence of male rats.
AB  - This study examined the effects of rhizomes of Alpinia calcarata Roscoe
      (Zingiberaceae) on male sexual competence and fertility, using a hot water
      extract (HWE) and rats. Different doses of HWE (150, 250 and 500 mg/kg) were
      orally administrated to male rats and their sexual behaviour was monitored (for
      15 min) 3 h later using receptive females. Fertility was determined in a separate
      group (with the highest dose) using a noncompetitive copulation test. In the
      sexual behaviour study, the HWE impaired the number of rats ejaculating and
      markedly prolonged the latency for ejaculation. Further, the number of rats
      mounting and intromitting, and the latencies for mounting and intromission were
      inhibited. Collectively, these observations indicate a strong aphrodisiac action.
      The other parameters remained unchanged indicating non-impairment in libido,
      sexual arousability, sexual vigour and sexual performance or penile erectile
      ability. However, a slight impairment was evident in sexual motivation (with the
      highest dose) in a partner preference test. In the fertility test, HWE induced
      profound oligozoospermia but fertility was uninhibited. The highest dose of HWE
      also elevated the serum testosterone level and the number of spontaneous penile
      erections rapidly and markedly. Further, the HWE was nontoxic. It is concluded
      that A. calcarata rhizomes possess a strong and safe oral aphrodisiac activity.

PMID- 16646523
TI  - Insulin modulates rat liver glucocorticoid receptor.
AB  - This investigation used cytosol fraction of rat liver to examine the effects of
      insulin (INS) on functional properties of glucocorticoid receptor (GR). Male
      Wistar rats (220-250 g b.wt.) were injected with INS (50 microg/200 g b.wt, i.p.)
      and 18 h after INS administration used for experiments. INS-stimulated
      dissociation of G-R complexes was significantly increased by 133% compared to
      control level. However, INS treatment significantly stimulated stability of GR
      protein by 138% above control value. Furthermore, results show that INS
      stimulated activation of formed cytosol [3H] TA-R complexes by 143% in respect to
      control. [3H]TA-R complexes from INS treated animals could be activated and
      accumulated at higher rate in cell nuclei of control animals. The physiological
      relevance of the data was confirmed by INS-related stimulation of Tryptophan
      oxigenase (TO) activity. It was observed that INS stimulated TO activity while
      INS injected to adrenalectomized rats, exhibited less effects compared to
      control. The results indicate that a glucocorticoid hormone (CORT) enhances INS
      induced stimulation of TO activity, as evidenced by enhanced enzyme activity.
      Presented data suggest: that INS treatment leads to modifications of the GR
      protein and the nuclear components and that INS activates the rat liver CORT
      signaling pathway which mediates, in part, the activity of TO.

PMID- 16646524
TI  - In vitro study of AMP-deaminase from fish (Cyprinus carpio) treated with
      hydrolyzable tannins.
AB  - AMP-deaminase (EC 3.5.4.6) is an enzyme responsible for stabilising adenylate
      energy changes. The properties of this enzyme are controlled by various ligands
      of hydrophobic nature. An investigation of enzyme activity alterations under the
      influence of natural phenolic acids (tannic, ellagic and gallic) which are
      soluble in water, could evidence the biological toxicity of these compounds. In
      our study purified AMP-deaminase isolated from white muscle of Cyprinus carpio
      was exposed to phenolic acids in the concentration range of 1 to 50 microM as
      well as to tannic acid in the presence of Cu2+ ions (5 microM). On the basis of
      the obtained results we can conclude that among the tested acids, gallic acid did
      not contribute to the change in AMP-deaminase activity, whereas ellagic acid
      diminished its activity at the highest concentration (50 microM). Tannic acid
      caused a significant decrease in the enzyme activity in comparison to control for
      all used concentrations. Cu2+ ions alone reduced the activity of AMP-deaminase
      for all studied concentrations. A combined action of a chosen Cu2+ ions
      concentration (5 microM) with tannic acid at the concentration higher than 2
      microM resulted in a decrease in the enzyme activity, but for lower tannic acid
      concentration of 1 microM the activity of AMP-deaminase was stimulated. These
      experiments showed that tannic acid may stop free radical chain reactions only at
      low concentrations (1 microM) in the presence of Cu2+ ions (5 microM).

PMID- 16646525
TI  - Low variability of internal transcribed spacer rDNA and trnL (UAA) intron
      sequences of several taxa in the Festuca ovina aggregate (POACEAE).
AB  - Identification and classification of numerous Festuca species is still a
      difficult problem due to the close morphological resemblance. The most difficult
      fine fescues to identify belong to the Festuca ovina aggregate, which is the
      largest group in the genus Festuca. Many taxons are considered to be separate
      species based on quantitative taxonomic characters, differences in ploidy level
      or the structure of sclerenchyma cells. In order to evaluate the taxonomic value
      of DNA-based markers, sequence analysis of the internal transcribed spacer (ITS1
      5.8S-ITS2) region and the chloroplast trnL (UAA) intron was performed in the ten
      most problematic fine fescues belonging to the Festuca ovina aggregate.
      Intraspecific ITS variants were found in a single case while in other cases only
      intragenomic ITS polymorphisms were detected with 1-2 ambiguous positions. Among
      the sequences of the trnL (UAA) intron even intragenomic polymorphisms were not
      detected in any of the Festuca species studied. Thus, the results do not support
      the species status of these ten taxa.

PMID- 16646526
TI  - The genotoxic effects of Logran on Hordeum vulgare L. and Triticum aestivum L.
AB  - In the present study, the cytogenetic effects of the herbicide Logran on root tip
      cells of Triticurn aestivum L. and Hordeum vulgare L. and changes of total
      protein content in root tip meristems were studied. The seeds of plants were
      treated with various concentrations of Logran (125, 250, 500 microg/ml) for 3 and
      6 h. The percentages of abnormal cells were seen to increase with increasing
      treatment period and concentrations. The most dominant types of observed
      abnormalities were C-mitosis, distributed metaphase and anaphase, stickiness. All
      the used concentrations of Logran significantly induced a number of chromosomal
      aberrations in root tip cells of Hordemrn vulgare L. and Triticum aestivum L.
      Logran also decreased mitotic index. The decrease of protein content in root tips
      of Triticum aestivum L. is significant at all the treated concentrations and
      treatment periods when compared with control.

PMID- 16646527
TI  - Synthesis of soluble heat shock proteins in seminal root tissues of some
      cultivated and wild wheat genotypes.
AB  - Effect of heat stress on the synthesis of soluble heat shock proteins (HSPs) and
      the regrowth in seminal roots of three cultivated and three wild wheat genotypes
      was examined. In regrowth experiments, 2-d-old etiolated seedlings were exposed
      to 23 (control), 32, 35, 37 and 38 degrees C for 24 h, and 35 and 37 degrees C
      (24 h) followed by 50 degrees C (1 h). The lengths of the seminal roots generally
      decreased significantly at the end of 48 and 72 h recovery growth periods at 35,
      37 and 38 degrees C temperature treatments compared with control. Genotypic
      variability was significant level at all temperature treatments for the seminal
      root length. Also, genotypic differences for the number of seminal roots were
      determined among the wheat cultivars and between the wild wheat species and the
      wheat cultivars at all temperature treatments; but genotypic differences among
      wild wheat species were only detected at 37-->50 degrees C treatment. Acquired
      thermotolerance for the seminal root length is over 50% at 37-->50 degrees C
      treatment. The genotypic variability of soluble heat shock proteins in seminal
      root tissues were analyzed by two-dimensional electrophoresis (2-DE). Total
      number of low molecular weight (LMW) HSPs was more than intermediate-(IMW) and
      high- (HMW) HSPs at high temperature treatments. The most of LMW HSPs which were
      generally of acidic character ranged between 14.2-30.7 kDa. The genotypes had
      both common (43 HSP spots between at least two genotypes and 23 HSP spots between
      37 and 37-->50 degrees C) and genotype-specific (72 HSP spots) LMW HSPs.

PMID- 16646528
TI  - In vitro pollen germination in Hypericum perforatum L. and Hypericum rumeliacum
      Boiss.
AB  - In vitro pollen germination and pollen tube growth investigations are valuable
      tools used in identification of the effects of environmental factors and
      genotypic differences on pollen viability, pollen germination and tube
      elongation. In this study pollen viability, in vitro pollen germination capacity,
      abnormality ratios and tube length in germinated pollens of Hypericum perforatum
      L. and H. rumeliacum Boiss. were investigated. Both of these species has spheroid
      shaped and tricolporate pollen grains. The diameters of Hypericum perforatum and
      H. rumeliacum pollens were found as 24 +/- 3 microm and 19 +/- 2 microm,
      respectively. Pollen viability of H. perforatum and H. rumeliacum was found as
      83% and 72%, respectively. The germination percentages were found as 12.85% for
      H. perforatum and 64.42% for H. rumeliacurm. Tube lengths in germinated pollens
      of both taxa were measured approximately as 95.25 +/- 38 microm in H. perforatum
      and 165.92 +/- 53 microm in H. rumeliacium 4 h after inoculation. In germinated
      pollen grains of H. perlbratum and H. rumeliacumn abnormality percentages were
      determined as 13.23% and 43.97%, respectively. In germinated pollens of these two
      species, highly significant (P < 0.00001) differences in in vitro germination
      percents and abnormality percents were observed. Abnormalities such as swollen
      tube tip, branched tube, spiralled tube and excessive tube formation were
      observed in pollen tubes. The results of this study showed that there were
      obvious differences in pollen germinability between these two species growing
      under the same environmental conditions.

PMID- 16646529
TI  - The effects of excess boron with niacin on Daucus carota L. (carrot) root callus.
AB  - Niacin (Nicotinic acid, B3 vitamin) may be involved in reduction of toxic effects
      of boron by regulating growth metabolism. This study was designed to examine
      whether external niacin treatment would improve the boron mobility in carrot
      callus cells or not. The results showed that excess boron caused tracheary
      inversions in meristematic root tissue, and also a shortage was seen in tracheary
      lengths with boric acid treatment. Boron excess induced the plant tolerance to
      water stress inverting the tracheary cells. This shortage converted nearly to
      normal size with niacin and boron treatment together. The results showed that
      boron mobility induced by niacin could reduce significantly the fresh and dry
      weight of carrot root cells, protein and ABA content was reduced also, in
      contrary, external boron and boron with niacin treatment considerable increased
      the two factors after one month stress. Fresh weight reduction and ABA content
      reduction indicated that niacin treatment caused water stress on the root cells
      of carrot, but boron treatment and boron with niacin treatment increased drought
      tolerance in carrot cells by increasing the both factors. In addition, turning
      the conversion of the length of the trachearies to their normal size proved that
      niacin treatment ended the polarizing effects of boron on cell walls.

PMID- 16646530
TI  - A novel aspect of NADPH production in ageing Penicillium chrysogenum.
AB  - NADPH is involved in many basically important anabolic processes. For a long
      time, pentose phosphate pathway (PPS) was regarded as the most important source
      of NADPH in fungi. Here we present evidence of a metabolic switch to an
      alternative NADPH-producing pathway in ageing Penicillium chrysogenum cultures,
      which involves NADP+ -specific isocitrate dehydrogenase (NADP+ -ID) rather than
      PPS enzymes. Considering the main biochemical functions of NADPH, we propose that
      NADP+ -ID could have deep impact on many physiological processes switched on
      glucose deprivation including proteinase production or penicillin biosynthesis.
      We also demonstrate that although the alternative pathway was inferior to PPS
      when the fungus was grown on well-utilisable carbon sources yet it could have an
      important role in fatty acid biosynthesis as well as in the maintenance of high
      intracellular NADPH/NADP+ ratios.

PMID- 16646531
TI  - Enhancement of mutanase production in Trichoderma harzianumby mutagenesis.
AB  - Conidia of Trichoderma harzianum F-340, an active producer of fungal mutanase,
      were mutagenized with physical and chemical mutagens used separately or in
      combination. After mutagenesis, the drop in conidia viability ranged from 0.004%
      to 71%. Among the applied mutagens, nitrosoguanidine gave the highest frequency
      of cultures with enhanced mutanase activity (98%). In total, 400 clones were
      isolated, and preliminarily evaluated for mutanase activity in flask
      microcultures. Eight most productive mutants were then quantified for mutanase
      production in shake flask cultures. The obtained results fully confirmed a great
      propensity of all the tested mutants to synthesize mutanase, the activity of
      which increased from 59 to 107% in relation to the parental T. harzianum culture.
      The best mutanase-overproducing mutant (T. harzianumn F-340-48), obtained with
      nitrosoguanidine, produced the enzyme activity of 1.36 U/ml (4.5 U/mg protein)
      after 4 days of incubation in shake flask culture. This productivity was almost
      twices higher than that achieved by the initial strain F-340, and, at present, is
      the best reported in the literature. The potential application of mutanase in
      dentistry is also discussed.

PMID- 16646532
TI  - Formaldehyde and some fully n-methylated substances in boar seminal fluids. Short
      communication.
AB  - On the basis of recent observations it is supposed that seminal fluids may
      contain--mainly in hydroxymethyl groups--formaldehyde (HCHO) and quaternary
      ammonium compounds as potential HCHO generators, therefore, preliminary
      investigations were carried out for the identification of these compounds in pig
      seminal fluids using OPLC, HPLC and MALDI MS techniques. The fresh pig seminal
      fluid was frozen in liquid nitrogen, powdered and aliquots (0.25 g) were treated
      with 0.7 ml ethanolic dimedone solution. The suspension was centrifuged and the
      clear supernatant was used for analysis by OPLC or after dilution with HPLC or
      MALDI MS technique. After OPLC separation of formaldemethone the fully N
      methylated compounds which are stayed on the start point were separated by OPLC
      using an other eluent system. It has been established that the HCHO is really a
      normal component of the pig seminal fluid, as well. It can be isolated and
      identified in dimedone adduct form. The measurable amount of HCHO depended on the
      concentration applied of dimedone. According to OPLC and MALDI MS investigations
      L-carnitine is the main quaternary ammonium compound in pig seminal fluid which
      can generate a protection of the sperm cells against environmental and other
      influences. Considerable differences have been found among individuals concerning
      concentrations of quaternary ammonium compounds in the seminal fluid of pigs.

PMID- 16646533
TI  - Excess of malignancies in grandparents of children with malformations? Short
      communication.
AB  - In a prospective study, the occurrence of malignancies in children referred to
      genetic counseling for congenital malformations, in their sibs, parents and
      grandparents was registered in 120 families by means of personal interviews. One
      hundred-and-twenty age matched subjects, admitted for acute respiratory
      infections or trauma, served as controls. No difference in the occurrence of
      tumors or leukemias between the two groups was found when the values of patients,
      sibs, and parents were compared. At the same time, the grandparents of probands
      with malformations had had significantly more malignancies than the grandparents
      of the controls. This may be explained by the fact that grandparents lived beyond
      the age of the usual onset of common cancers and leukemias.

PMID- 16646534
TI  - HealthCom media launches new journal for the American Nurses Association;
      American Nurse Today.

PMID- 16646535
TI  - Kentucky ARNP authority to prescribe scheduled drugs.

PMID- 16646536
TI  - President's pen.

PMID- 16646537
TI  - Centennial celebration--a historical journey through District 4 (Breckinridge,
      Grayson, Green, Hardin, Hart, Larue, Meade, Nelson & Taylor Counties).

PMID- 16646538
TI  - Self-protecting behaviors in college females.

PMID- 16646539
TI  - Evidence-based practices to promote breastfeeding.

PMID- 16646540
TI  - Defending nurses rights and responsibilities.

PMID- 16646541
TI  - Detection of postpartum depression at well-child visits.

PMID- 16646542
TI  - Kentucky nurse blows the whistle--and wins.

PMID- 16646543
TI  - KNA long-term care program.

PMID- 16646544
TI  - About those political parties.

PMID- 16646545
TI  - Reputations: victims of the marketing machine.

PMID- 16646547
TI  - Volunteers give kids a smile.

PMID- 16646546
TI  - Politics in dentistry.

PMID- 16646548
TI  - Partnerships: the benefits, pitfalls and elements for success.

PMID- 16646549
TI  - Sweat the small stuff.

PMID- 16646550
TI  - The biggest problem with dental implants: the dentist.

PMID- 16646551
TI  - Colds, flus, aches, pains.

PMID- 16646552
TI  - Robert Edwin Blackwell: exemplar of dentistry's ethics.

PMID- 16646553
TI  - Too much of a good thing.

PMID- 16646554
TI  - 4 reasons to love AHPs--and 4 reasons to leave them.

PMID- 16646555
TI  - Five ways Part D plans are positioning for new business.

PMID- 16646556
TI  - Physicians can give P4P a test run--with no pay at stake.

PMID- 16646557
TI  - Is hypercapnea a predictor of better survival in the patients who underwent
      mechanical ventilation for chronic obstructive pulmonary disease (COPD)?
AB  - BACKGROUND: There are contradictory reports concerning hypercapnia as a predictor
      of a better outcome in COPD. This study examined the clinical implications of
      hypercapnea in COPD patients (M:F = 59:19) who required mechanical ventilation.
      METHODS: The clinical parameters at the time of MICU admission, the total
      ventilation time, the APACHE II score and the pulmonary function testing were
      retrospectively analyzed between the survivors and nonsurvivors. RESULTS:
      Univariate analysis showed that compared with the nonsurvivors, the survivors had
      lower AaDO2 values (59.8 +/- 53.5 vs. 105.0 +/- 73.3 mmHg, p=0.000), higher PaCO2
      values (64.9 +/- 16.0 vs. 48.9 +/- 17.8 mmHg, p=0.000), lower APACHE II scores
      (19.0 +/- 3.8 vs. 24.1 +/- 5.1, p=0.002), the more frequent application of
      initial noninvasive positive pressure ventilation (44.0 vs. 14.3%, p=0.008), and
      a lower combined rate of septic shock (4.0 vs. 39.3%, p=0.000). Multivariate
      analysis revealed that a lower PaCO2 (OR: 0.94, p=0.008), the presence of septic
      shock (OR: 10.16, p=0.011), a higher APACHE II score (OR: 1.22, p=0.040) and a
      longer ventilation time (OR: 1.002, p=0.041) were the risk factors for mortality.
      A lower PaCO2 was also verified as the predictor. for mortality by multivariate
      analysis when excluding septic shock. CONCLUSIONS: Hypercapnia at admission is
      thought to be an independent predictor of better survival for the COPD patients
      who require mechanical ventilation.

PMID- 16646558
TI  - Severe airway hyperresponsiveness in school-aged boys with a high body mass
      index.
AB  - BACKGROUND: An association between obesity and asthma has been reported. The
      prevalence of airway hyperresponsiveness (AHR), results of skin prick tests, body
      mass index (BMI), and asthma symptoms were examined in schoolchildren. METHODS:
      The results of BMI (kg/m2) determination, skin prick testing, spirometry, asthma
      questionnaires, and methacholine challenge tests were obtained in a cross
      sectional survey of 667 schoolchildren. The methacholine concentration causing a
      20% fall in FEV1 (PC20) was used as the threshold of AHR. If the PC20 was less
      than 16 mg/mL, the subject was considered to have methachloine mediated AHR.
      RESULTS: The mean BMI was 17.1 +/- 0.09 kg/m2. The prevalence of AHR was 42.70%.
      The sensitization rate to common inhalant allergens was 30.3%. PC20 in children
      with BMIs > or = 17.1 kg/m2 was significantly lower than that in children with
      BMIs 17.1 kg/m2. The mean BMIs of boys and girls were not significantly
      different. The levels of PC20 by sex were not different. The children were
      grouped by sex into percentile of BMI. PC20 in boys was lower in the obese group
      than in the non-weight and overweight groups (p<0.05). PC20 in boys and girls
      with atopy was significantly lower than in those without atopy. In a multiple
      logistic regression model that included all of the children and adjusted for
      confounding variables, independent associations with AHR were seen with BMI,
      asthma symptoms, and atopy. CONCLUSIONS: BMI had an association with AHR in
      school-age boys.

PMID- 16646559
TI  - The role of endoscopic surgery for completely obstructive endobronchial benign
      tumor.
AB  - BACKGROUND: The improving techniques of therapeutic bronchoscopy have been
      replacing conventional surgery for resecting endobronchial benign tumor. However,
      there could be some limitation for performing bronchoscopic intervention for the
      patients with complete bronchial obstruction. To evaluate the role of endoscopic
      surgery for completely obstructive endobronchial benign tumor, we retrospectively
      reviewed the medical records of 7 patients who underwent bronchoscopic resection
      due to completely obstructive benign tumor. METHODS: Rigid bronchoscopy was
      performed under general anesthesia. After the stalk of tumor was identified with
      using a 1 mm biopsy forceps as a probe, a Nd-YAG laser was used to coagulate the
      stalk of tumor. The tumor was then removed. RESULTS: Bronchoscopic resection was
      successful in 6 out of 7 patients. The histological diagnoses were 3 leiomyomas,
      3 harmatomas and 1 lipoma. There was no mortality in our study. Pneumomediastinum
      developed in 1 patient, and this patient was treated with 3 days of oxygen
      therapy. In 5 out of the 6 successful patients, there was no recurrence for a
      median of 35 months. In 1 patient, leiomyoma recurred after 17 months, and this
      was treated by pneumonectomy. CONCLUSIONS: Endoscopic surgery could be applied to
      the patients with completely obstructive endobronchial benign tumor.

PMID- 16646560
TI  - Hepatocyte growth factor/c-met signaling in regulating urokinase plasminogen
      activator in human stomach cancer: A potential therapeutic target for human
      stomach cancer.
AB  - BACKGROUND: Up-regulation of the hepatocyte growth factor (HGF), its
      transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen
      activator (uPA), is associated with the development and metastasis of various
      types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates
      cancer progression and metastasis are unclear. METHODS: We investigated the roles
      of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach
      cancer cell lines. RESULTS: Treatment with HGF increased c-Met phosphorylation in
      a dose-dependent manner, as well as increasing cell proliferation. HGF treatment
      also increased the protein level and the activity of uPA in NUGC-3 and MKN-28
      cells. A monoclonal antibody against human uPA receptor (uPAR), mAb 3936,
      inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down
      regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion in
      NUGC-3 cells. CONCLUSIONS: These results suggest that NUGC-3 and MKN-28 cells
      express functional c-Met, which may provide a therapeutic target for interfering
      with metastases of cancer cells by inhibiting uPA and uPAR-mediated proteolysis.

PMID- 16646561
TI  - P53 genetic polymorphism of gastric cancer in Korea.
AB  - BACKGROUND: Deletion or functional loss of the p53 tumor suppression gene plays a
      role in oncogenic transformation. The codon 72 polymorphism on exon 4 in the p53
      gene produces variant proteins with either arginine (Arg) or proline (Pro), and
      is associated with an increased susceptibility of cancers of the lung, esophagus,
      breast, cervix and nasopharynx on a genetic basis. We designed this study to
      evaluate the influence of the p53 codon 72 polymorphism on gastric cancer in
      Korea. METHODS: We extracted the peripheral blood samples in 84 patients with
      gastric cancer, 66 patients with H. pylori-associated chronic gastritis and 43
      controls without H. pylori infection. PCR-RFLP analysis was performed to detect
      p53 codon 72 polymorphism in these patients. RESULTS: There was no specific
      genotype of p53 polymorphism in the gastric cancer group compared to the other
      groups and no difference in genotypes by histologic subtypes. Classified by tumor
      location, Pro/Pro genotype was associated with an increase in proximal cancer and
      Arg/Arg genotype with distal cancer. As the frequency of p53 Arg allele
      increased, the cancer was of a more poorly differentiated type. CONCLUSIONS: The
      specific genotype of p53 polymorphism seems to correlate with tumor location.
      Increased frequency of p53 Arg allele is associated with more poorly
      differentiated cancers.

PMID- 16646562
TI  - Association of serum albumin and homocysteine levels and cardio-ankle vascular
      index in patients with continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: The cardio-ankle vascular index (CAVI) is a newly developed
      arteriosclerotic measurement that has been proposed as an alternative to aortic
      pulse-wave velocity (PWV). The present study used the CAVI to identify the main
      factors associated with arteriosclerosis in continuous ambulatory peritoneal
      dialysis (CAPD) patients. METHODS: Fifteen CAPD patients were enrolled in the
      study. The CAVI is independent of the pressure and vascular reflection between
      the heart valve and the ankle. Serum albumin, uric acid, total calcium,
      phosphorus, lipid levels, high-sensitivity C-reactive protein and homocysteine
      concentrations in CAPD patients were measured using standard methods. Total body
      fat mass, truncal and non-truncal fat mass and lean body mass were measured using
      dual energy X-ray absorptiometry with a Lunar DPX-L scanner. RESULTS: CAPD
      patients had a mean CAVI of 9.37 +/- 3.16 m/sec, which was higher than the
      general population. The CAVI was negatively correlated with the serum albumin
      concentration (r=-0.548; p=0.034). Stepwise regression analysis showed that both
      the serum albumin concentration (beta=-0.643, p=0.013) and the serum homocysteine
      level (beta=0.486, p=0.004) were independently associated with the CAVI.
      CONCLUSIONS: An increase in CAVI was independently associated with both serum
      albumin and homocysteine level.

PMID- 16646563
TI  - Acute respiratory failure associated with cryptococcal pneumonia and disseminated
      cryptococcosis in an AIDS patient.
AB  - A 36-year-old homosexual Mexican man was admitted to our hospital, with a 30-day
      history of fever and headache. Upon cerebrospinal fluid examination, the
      patient's white blood cell count was 1,580/L, total protein was 26 mg/dL, sugar
      was 17 mg/dL, and his intracranial pressure was 23 cmH2O. The patient was
      diagnosed with HIV (Human Immunodeficiency Virus) infection by serum Western
      blotting. Cryptococcus neoformans was isolated in cultures of the patient's blood
      and cerebrospinal fluids. Chest computerized tomography revealed diffuse
      reticulonodular infiltration and a ground-glass appearance in both perihilar
      regions, suggestive of either Pneumocystis carinii pneumonia or cryptococcal
      pneumonia. On the patient's 6th day in our hospital, bronchoalveolar lavage and
      transbronchial lung biopsy were conducted via bronchoscopy, and a pathologic
      examination of lung biopsy specimens revealed signs of cryptococcal pneumonia.
      This patient died on his 14th day in our hospital, as the result of acute
      respiratory failure, associated with cryptococcal pneumonia and disseminated
      cryptococcosis.

PMID- 16646564
TI  - Unpredicted severe toxicity after 5-fluorouracil treatment due to
      dihydropyrimidine dehydrogenase deficiency.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in
      the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are
      at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with
      gastric cancer underwent a curative operation, followed by adjuvant chemotherapy
      consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the
      patient manifested grade 2 mucositis and febrile neutropenia, and when her
      treatment was subsequently continued with doxifluridine she developed severe
      mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level
      was lower than that in a control group. Thus, when considering the routine use of
      5-FU for the treatment of cancer patients, an analysis of DPD activity or
      screening for DPD mutations is warranted in confined patients who experience
      unpredicted severe toxicity after initial 5-FU administration, even though DPD
      deficiency is a rare metabolic defect.

PMID- 16646565
TI  - Epstein-Barr virus-associated Hodgkin's disease following renal transplantation.
AB  - Post-transplant lymphoproliferative disorders (PTLD) have been recognized as a
      complication of immunosuppression and occur with a reported incidence of 1 to 8%
      of recipients receiving solid organ transplantation. PTLD are classified into two
      major categories, polymorphic and monomorphic PTLD. The majority of the
      monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. Hodgkin's
      disease is not part of the typical spectrum of PTLD; however, it has been rarely
      reported. We describe a case of Hodgkin's disease following renal
      transplantation. A 41-year-old man developed right cervical lymphadenopathy
      following renal transplantation 116 months previously for chronic renal failure
      of unknown origin. He had been taking cyclosporine, mycophenolate mofetil and
      prednisone. A lymph node biopsy revealed mixed cellularity Hodgkin's disease.
      Immunohistochemical staining was positive for CD30 and EBV-latent membrane
      protein-1. No other site of disease was identified. The immunosuppressive agents
      were reduced (mycophenolate mofetil was discontinued, cyclosporine dose reduced
      from 200 mg to 150 mg and prednisone continued at 5 mg). After 2 cycles of ABVD
      followed by radiation therapy (3600 cGy), he achieved complete remission.

PMID- 16646566
TI  - A case of Behcet's disease with pericarditis, thrombotic thrombocytopenic
      purpura, deep vein thrombosis and coronary artery pseudo aneurysm.
AB  - Behcet's disease with concomitant thrombotic thrombocytopenic purpura (TTP),
      coronary artery stenosis and coronary artery pseudo aneurysm is rare. Here we
      report a case of Behcet's disease with several cardiovascular complications,
      namely: pericarditis, deep vein thrombosis (DVT), TTP, coronary artery stenosis,
      and a coronary artery pseudo aneurysm. A 37-year-old female presented with sudden
      dyspnea and syncope at our emergency room and underwent pericardiectomy and
      pericardial window formation for the diagnosis of cardiac tamponade with acute
      hemorrhagic pericarditis. Thereafter, TTP and DVT complicated her illness. After
      confirmation of Behcet's disease on the basis of a history of recurrent oral and
      genital ulcers and erythema nodosum, remission was achieved after treatment with
      methylprednisolone pulse therapy, colchicine, catheter directed thrombolysis and
      thrombectomy. However, whilst maintaining anticoagulation therapy, a newly
      developed pericardial aneurysmal dilatation was noted on follow-up radiologic
      evaluation. Further evaluation revealed right coronary artery stenosis and a left
      coronary artery pseudo aneurysm; these additional problems were treated with the
      nonsurgical insertion of an endovascular graft stent. At the time of writing
      three months later after stent insertion, the aneurysm has continued to regress
      and no additional complications have intervened with combined immunosuppressive
      therapy.

PMID- 16646567
TI  - Peripheral T-cell lymphoma-unspecified (PTCL-U) presenting with hypereosinophilic
      syndrome and pleural effusions.
AB  - Hypereosinophilic syndrome (HES) is a clinical disorder characterized by
      persistent eosinophilia and systemic involvement, in which a specific causative
      factor for the eosinophilia cannot be verified during a certain period of time.
      There have been only a few reported cases of this syndrome associated with
      malignant lymphoma. We report a case of peripheral T-cell lymphoma-unspecified
      with hypereosinophilic syndrome. The patient was a 42-year-old woman with an
      uncontrolled fever and a sore throat. Eosinophilia was observed on the peripheral
      blood smear. We confirmed the diagnosis by bone marrow and liver biopsies:. A
      bone marrow aspiration demonstrated markedly increased eosinophils (24.8%), and a
      liver biopsy demonstrated infiltration by scattered eosinophils and atypical
      lymphoid cells, which were confirmed to be T-cell lymphoma cells. This case was a
      distinctive presentation of peripheral T-cell lymphoma with hypereosinophilic
      syndrome, probably due to a paraneoplastic condition.

PMID- 16646568
TI  - A case of gastric tuberculosis mimicking advanced gastric cancer.
AB  - Tuberculosis of the stomach is quite rare, both as a primary or secondary
      infection. It can present as a facet of a multiorgan disease process or may
      result from immunodeficiency. Here, we report a rare, interesting case of gastric
      tuberculosis which morphologically mimicked advanced gastric cancer in a young,
      immunocompetent patient presenting with hematemesis and melena. The disease was
      diagnosed by biopsy, and responded well to antituberculosis medication without
      surgery. Clinicians must bear in mind that, even in the absence of
      immunodeficiency, as in this case, tuberculosis can involve any site in the
      gastrointestinal tract and may present with a variety of characteristics. Gastric
      tuberculosis should always be part of the differential diagnosis of chronic
      infiltrative lesions in the stomach.

PMID- 16646569
TI  - Delayed puberty due to pituitary stalk dysgenesis and ectopic neurohypophysis.
AB  - Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was
      referred to our clinic because of the absence of the development of secondary
      sexual characteristics. The patient had no complaints of physical discomfort.
      Random serum testosterone and luteinizing hormone level were obtained and found
      to be low. The combined pituitary function stimulation test revealed a partial
      hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and
      showed decreased pituitary stalk enhancement and ectopic neurohypophysis.
      Therefore, we conclude that the delayed puberty was a result of hypopituitarism
      due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was
      started on hormone replacement therapy and gradually developed secondary sexual
      characteristics.

PMID- 16646570
TI  - A patient with primary squamous cell carcinoma of the thyroid intermingled with
      follicular thyroid carcinoma that remains alive more than 8 years after
      diagnosis.
AB  - Primary squamous cell carcinoma of the thyroid is an extremely rare tumor with a
      highly aggressive clinical course. We report here on a patient with primary
      squamous cell carcinoma of the thyroid who remains alive more than 8 years after
      diagnosis. A 56-year-old man presented with a hoarse voice and a rapidly
      progressing mass on the right side of the thyroid gland. The patient underwent a
      total thyroidectomy without neck lymph node dissection. Histopathologic findings
      revealed primary squamous cell carcinoma combined with follicular carcinoma of
      the thyroid. The tumors metastasized to the cervical lymph nodes, thoracic spine
      and lung. He underwent 5000 rads of adjuvant radiotherapy to the neck. TSH
      suppressive therapy with L-thyroxine was administered alone rather than
      radioactive iodine therapy or chemotherapy. The patient's clinical course has
      been remarkable over the first 7 years; he has remained stable except for a
      transient paraplegia due to nerve compression. The patient underwent colectomy
      for the diagnosis of a colon cancer. Recent evaluation has revealed a new lesion
      in the lung; this was diagnosed as metastatic follicular carcinoma originating
      from the thyroid. High dose radioactive iodine therapy was administered, and he
      remains alive in stable condition.

PMID- 16646571
TI  - Hemobilia from ruptured hepatic artery aneurysm in polyarteritis nodosa.
AB  - Hemobilia, in patients with the diagnosis of polyarteritis nodosa, is rare at
      clinical presentation and has a grave prognosis. We describe a case of massive
      hemobilia, due to aneurysmal rupture, in a patient with polyarteritis nodosa. A
      39-year-old man was admitted to the hospital with upper abdominal pain. The
      patient had a history of partial small bowel resection, for intestinal
      infarction, about 5 years prior to this presentation. Abdominal computed
      tomography demonstrated multiple high attenuation areas in the bile duct and
      gallbladder. Hemobilia with blood seepage was visualized on endoscopic retrograde
      cholangiopancreatography; this bleeding stopped spontaneously. The following day,
      the patient developed a massive gastrointestinal bleed with resultant hypovolemic
      shock. Emergent hepatic angiogram revealed multiple microaneurysms; a
      communication was identified between a branch of the left hepatic artery and the
      bile duct. Hepatic arterial embolization was successfully performed. The
      underlying disease, polyarteritis nodosa, was managed with prednisolone and
      cyclophosphamide.

PMID- 16646572
TI  - A case of pulmonary cryptococcosis by capsule-deficient Cryptococcus neoformans.
AB  - Pulmonary infection by capsule-deficient Cryptococcus neoformans (CDCN) is a very
      rare form of pneumonia and it is seldom seen in the immunocompetent host. The
      authors experienced a case of pulmonary cryptococcosis by CDCN in 25-year-old
      woman who was without any significant underlying disease. The diagnosis was made
      from the percutaneous lung biopsy and special tissue staining, including Fontana
      Masson silver (FMS) staining. Fungal culture confirmed the diagnosis afterward.
      Her clinical and radiologic features improved under treatment with fluconazol.
      It's known that CDCN is not so readily confirmed because fungal culture does not
      always result in growth of the organism and the empirical fungal stain is not
      helpful for the differentiation between CDCN and the other infections that are
      caused by the nonencapsulated yeast-like organisms. In this report, we emphasize
      the diagnostic value of performing FMS staining for differentiating a CDCN
      infection from the other confusing nonencapsulated yeast-like organisms.

PMID- 16646573
TI  - Genetic and epigenetic biomarkers in cancer : improving diagnosis, risk
      assessment, and disease stratification.
AB  - Gene expression patterns change during the initiation, progression, and
      development of cancer, as a result of both genetic and epigenetic mechanisms.
      Genetic changes arise due to irreversible changes in the nucleotide sequence,
      whereas epigenetic changes occur due to changes in chromatin conformation,
      histone acetylation, and methylation of the CpG islands located primarily in the
      promoter region of a gene. Both genetic and epigenetic markers can potentially be
      utilized to identify different stages of tumor development. Several such markers
      exhibit high sensitivity and specificity for different tumor types and can be
      assayed in biofluids and other specimens collected by noninvasive technologies.
      In spite of the availability of large numbers of diagnostic markers, only a few
      have been clinically validated so far. The current status and the challenges in
      the field of genetic and epigenetic markers in cancer diagnosis, risk assessment,
      and disease stratification are discussed.

PMID- 16646574
TI  - Diagnostics for herpes simplex virus: is PCR the new gold standard?
AB  - Herpes simplex virus (HSV) is one of the most common, yet frequently overlooked,
      sexually transmitted infections. Since the type of HSV infection affects
      prognosis and subsequent counseling, type-specific testing to distinguish HSV-1
      from HSV-2 is recommended. Although PCR has been the diagnostic standard for HSV
      infections of the central nervous system, until now viral culture has been the
      test of choice for HSV genital infection. However, HSV PCR, with its consistently
      and substantially higher rate of HSV detection, will likely replace viral culture
      as the gold standard for the diagnosis of genital herpes in people with active
      mucocutaneous lesions, regardless of anatomic location or viral type.
      Alternatively, type-specific serologic tests based on glycoprotein G should be
      the test of choice to establish the diagnosis of HSV infection when no active
      lesion is present. Given the difficulty in making the clinical diagnosis of HSV,
      the growing worldwide prevalence of genital herpes and the availability of
      effective antiviral therapy, there is an increased demand for rapid, accurate
      laboratory diagnosis of patients with HSV.

PMID- 16646575
TI  - Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in
      healthy individuals.
AB  - Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically
      expressed enzymes that are involved in the metabolic inactivation of several
      drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and
      anticoagulants. Many of these drugs have a narrow therapeutic index, and growing
      evidence indicates a prominent role of CYP2C8 and CYP2C9 polymorphisms in the
      therapeutic efficacy and in the development of adverse effects among patients
      treated with drugs that are CYP2C8 or CYP2C9 substrates. In this review, we
      summarize present knowledge on human variability in the frequency of variant
      CYP2C8 and CYP2C9 alleles. Besides an expected interethnic variability in allele
      frequencies, a large intraethnic variability exists. Among Asian subjects, for
      example, statistically significant differences (p < 0.0001) in CYP2C9*3 allele
      frequencies between Chinese and Japanese individuals have been reported. In
      addition, individuals from East Asia present different allele frequencies for
      CYP2C9*2 and CYP2C9*3 compared with South Asian subjects (p < 0.0001). Among
      Caucasian Europeans, statistically significant differences for the frequency of
      CYP2C8*3, CYP2C9*2, and CYP2C9*3 exist (p < 0.0001). This indicates that Asian
      individuals or Caucasian European individuals cannot be considered as homogeneous
      groups regarding CYP2C8 or CYP2C9 allele frequencies. Caucasian American subjects
      also show a large variability in allele frequencies, which is likely to be
      related to ethnic ancestry. A higher frequency of variant CYP2C8 and CYP2C9
      alleles is expected among Caucasian Americans with South European ancestry than
      in individuals with North European ancestry. The findings summarized in this
      review suggest that among individuals with Asian or European ancestry,
      intraethnic differences in the risk of developing adverse effects with drugs that
      are CYP2C8 or CYP2C9 substrates are to be expected. In addition, the observed
      intraethnic variability reinforces the need for proper selection of control
      subjects and points against the use of surrogate control groups for studies
      involving association of CYP2C8 or CYP2C9 alleles with adverse drug reactions or
      spontaneous diseases.

PMID- 16646576
TI  - Detection of circulating tumor cells in peripheral blood of breast cancer
      patients during or after therapy using a multigene real-time RT-PCR assay.
AB  - AIM: To evaluate the utility of a multigene real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) assay to detect circulating tumor cells in
      peripheral blood specimens of breast cancer patients during or after treatment.
      METHOD: Using this assay, peripheral blood samples were analyzed for expression
      levels of mammaglobin and three complementary transcribed breast cancer-specific
      genes: B305D, gamma-aminobutyrate type A receptor pi subunit (GABA pi; GABRP),
      and B726P. We examined 172 blood specimens from 82 breast cancer patients during
      or after therapy for the presence of circulating tumor cells using the multigene
      real-time RT-PCR assay. RESULTS: In 63.4% of the blood samples, a positive signal
      for mammaglobin and/or three breast cancer-associated gene transcripts was
      detected. Of breast cancer patients, 75.6% had at least one positive blood
      sample. Blood specimens from 51 of 53 healthy female volunteers tested negative
      in the assay whereas two samples had a low expression signal. In addition, three
      patients were monitored for more than a year during their adjuvant therapy
      treatment. CONCLUSION: This assay could be a valuable tool for monitoring breast
      cancer patients during and after therapy.

PMID- 16646577
TI  - Brushing of oral mucosa for diagnosis of HPV infection in patients with
      potentially malignant and malignant oral lesions.
AB  - INTRODUCTION: Adequate brushing of oral mucosa is important for accurate human
      papillomavirus (HPV) detection in potentially malignant (oral leukoplakia [OL],
      oral lichen planus [OLP]) and malignant (oral squamous cell carcinoma [OSCC])
      lesions. Since various factors may limit the adequacy of oral brushing and,
      consequently, the accuracy of HPV detection, modified sampling procedures should
      be evaluated for their effect on HPV frequency and/or types detected. AIM: To
      compare the HPV frequency in samples obtained by brushing the lesion site with
      the frequency in samples obtained by brushing an apparently normal adjacent site.
      The correlation between HPV frequency and keratinization of the site affected by
      the lesion, as well as sociodemographic variables (age, sex, smoking and drinking
      habits), was also examined. METHODS: HPV DNA was detected in brushing samples
      from 50 patients with OL, 49 with OLP, and 17 with OSCC. Polymerase chain
      reaction (PCR) amplification was performed by MY09/MY11 and GP05+/GP06+ primers;
      the HPV type was identified by DNA sequencing and a reverse hybridization (line
      probe) assay. Data were analyzed by the Z test, the Fisher's exact test, the chi
      square test, odds ratio (OR), and a logistic regression model. RESULTS: HPV DNA
      was detected in 22% of samples from lesion sites and in 16% of samples from
      adjacent sites (p = 0.22) in patients with OL, in 24.5% and 22.4% of samples from
      lesion and adjacent sites, respectively, in patients with OLP (p = 0.40), and in
      35.3% and 41.2% of samples from lesion and adjacent sites, respectively, in
      patients with OSCC (p = 0.36). Lesions adjacent to HPV-positive normal sites had
      an increased rate of HPV detection (OR = 30; 95% CI 9.57, 94.1). HPV-18 was the
      most frequent genotype, followed by HPV-6, -16, -33, and -53. HPV prevalence was
      reduced in lesions at keratinized sites (14.5%) compared with non-keratinized
      sites (34.4%; p = 0.007; OR = 0.32; 95% CI 0.13, 0.81). DISCUSSION: In patients
      with OL, OLP, or OSCC, a high prevalence of HPV infection was shown in apparently
      normal sites adjacent to lesion sites infected by HPV. The lower HPV frequency in
      lesions at keratinized sites suggests that HPV detection by lesion brushing is
      affected by keratinization. The keratinized epithelium may be less susceptible to
      HPV infection or, alternatively, the highly proliferative activity in non
      keratinized sites may predispose to HPV infection. CONCLUSION: Results from this
      study indicate that taking samples from normal sites adjacent to oral lesions may
      be of value in HPV detection, particularly when the lesions are located at
      keratinized sites. This sampling procedure may allow more accurate diagnosis of
      HPV infection compared with sampling only the lesion site, and may also represent
      a reliable method to investigate the biological characteristics of HPV infection
      and related oral carcinogenesis.

PMID- 16646578
TI  - T-SPOT.TB: an in vitro diagnostic assay measuring T-cell reaction to
      Mycobacterium tuberculosis-specific antigens.
AB  - The overall sensitivity of the RD1 ELISPOT assay (T-SPO.TB), which counts T cells
      sensitized to specific Mycobacterium tuberculosis peptide sequences, was 81-97%
      in populations with confirmed tuberculosis, in whom 39-78% had immunosuppressive
      conditions. In patients with confirmed tuberculosis, the respective RD1 ELISPOT
      versus tuberculin skin test (TST) sensitivities were 100% versus 89% in adults
      and 77% versus 35% in children (of whom 39% were HIV-positive). In contrast to
      that of the TST, the sensitivity of the RD1 ELISPOT assay was not significantly
      affected by age <36 months, or the immunological or nutritional status of the
      subjects. Specificity was 100% in two UK-based studies. Isolated false positives
      have been recorded in patients infected with non-tuberculous M. kansasii. A study
      investigating latent tuberculosis infection found no significant difference in
      results between HIV-positive and -negative participants for the RD1 ELISPOT
      assay, while the TST varied significantly with HIV status. Contact-tracing
      studies have demonstrated concordance between the RD1 ELISPOT assay and the TST
      of 65-89%. There is a significant correlation between a positive result and the
      degree of exposure to the index case for the RD1 ELISPOT assay, but not for the
      TST, in contact-tracing studies. Unlike the TST, the RD1 ELISPOT assay is not
      confounded by bacille Calmette-Guerin vaccination.

PMID- 16646581
TI  - Cardiac connexins: genes to nexus.
AB  - Gap junctions are formed of at least 20 connexin proteins in mammals and possibly
      pannexins as well. Of the connexins, at least 5 (Cx30.2, Cx37, Cx40, Cx43 and
      Cx45) are prominently expressed in the heart and each shows regional and cell
      type specific expression. Contributions of each of these connexins to heart
      function has been in many cases illuminated by connexin null mice. The cardiac
      connexin genes whose genomic organization and transcriptional controls have been
      studied most thoroughly indicate more complex possibilities for alternate
      promoter usage than originally thought as well a multiple transcription factor
      binding sites; presumably, such complexity governs developmental timing and
      regional connexin expression patterns. The structure of cardiac connexin proteins
      indicate four primarily alpha-helical transmembrane domains, cytoplasmic amino
      and carboxyl termini and a cytoplasmic loop, all of which contain some regions of
      alpha-helix, and extracellular loops that are primarily Beta-structure. A number
      of proteins that bind to cardiac connexins are known, and more are certain to be
      discovered, linking the connexin into an intercellular signaling complex, the
      nexus. Binding sites may either correspond to structured regions within the
      connexin molecules or be unstructured, leading to presumably low-affinity and
      dynamic interactions.

PMID- 16646582
TI  - Physiology of cardiovascular gap junctions.
AB  - Cardiac gap junction channels are crucial for conduction of the electric impulse.
      Between cardiomyocytes there exist gap junctions constructed from connexin40
      (Cx40), Cx43 and Cx45. A fourth isoform, Cx37, is expressed in the endothelial
      lining. Each of these channel types possesses specific properties and their
      functioning is regulated by various mechanisms. In this chapter we compare the
      physiological differences between these channels and discuss the factors involved
      in modulation of channel properties. Next, we evaluate how alterations in
      expression and differential regulation of channel properties affect cardiac
      impulse propagation.

PMID- 16646583
TI  - Role of connexin43-interacting proteins at gap junctions.
AB  - Gap junctions are arrays of cell-to-cell channels that allow diffusion of small
      molecules between neighboring cells. The individual channels are formed by the
      four-transmembrane connexin (Cx) proteins. Recently, multiple proteins have been
      found to interact at the cytoplasmic site with the most abundant connexin, Cx43,
      but physiological data about the role of these interactions is scarce. Here,
      molecular detail about Cx43 interactions is presented and the putative roles of
      Cx43-interacting proteins are discussed. Emphasis is on new insights into the
      interactions of c-Src and ZO-1 with Cx43, interacting proteins discovered within
      the last 2 years (drebrin, CIP85, CCN3), and feedback between gap junctions,
      adherens junctions (N-cadherin and catenins) and the cytoskeleton (microtubules
      and actin).

PMID- 16646584
TI  - Life cycle of connexins: regulation of connexin synthesis and degradation.
AB  - Gap-junction-forming connexins (Cx) exhibit a complex life cycle which is
      regulated at various levels. First, the promoter regions and binding of
      transcription factors to them control the transcription of the connexin genes.
      Translation of Cx-mRNA seems to be enabled by internal ribosome entry site
      elements allowing translation even under stress conditions. The newly synthetized
      Cx protein (monomeric) is transferred to the Golgi apparatus, oligomerized,
      transferred to the plasma membrane and incorporated into gap junction plaques.
      Two principal pathways for degradation of Cx could be defined: (a) lysosomal and
      (b) proteasomal degradation, including phosphorylation and ubiquitination as well
      as the internalization of complete gap junction channels as annular gap junctions
      doomed to degradation. In the present article, the various steps of the life
      cycle of cardiac connexins and its regulation are reviewed.

PMID- 16646585
TI  - Gap junctions and propagation of the cardiac action potential.
AB  - Pacemaker cells in the heart generate periodic electrical signals that are
      conducted to the working myocardium via the specialized conduction system.
      Effective cell-to-cell communication is critical for rapid, uniform conduction of
      cardiac action potentials-- a prerequisite for effective, synchronized cardiac
      contraction. Local circuit currents form the basis of the depolarization wave
      front in the working myocardium. These currents flow from cell to cell via gap
      junction channels. In this chapter, we trace the path of the action potential
      from its generation in the sinus node to propagation through the working
      myocardium, with a detailed discussion of the role of gap junctions. First, we
      review the transmembrane ionic currents and the basic principles of conduction of
      the action potential to the working myocardium via the specialized tissues of the
      heart. Next, we consider the relative contribution of cell geometry, size, and
      gap junction conductance. These factors are examined in terms of their source-to
      sink relationships. Lastly, we will discuss new insights into the importance of
      gap junctions in cardiac conduction in health and disease which have been gained
      from high resolution optical mapping in connexin-deficient mice.

PMID- 16646586
TI  - Micropatterns of propagation.
AB  - Alterations in microscopic conduction could contribute to microreentry and
      arrhythmogenesis in pathological settings. This chapter reviews microconduction
      in the ventricular myocardium. Gap junctions play a significant role in
      longitudinal and transverse propagation of the action potential wavefront in the
      ventricle. Studies of microscopic conduction in patterned cultures of neonatal
      rodent myocytes have provided novel insights into the role of gap junctions, the
      effects of uncoupling versus altered excitability, and the contribution of
      discontinuities and branching. Decreased gap junctional coupling can contribute
      to slowing of conduction and development of unidirectional block. However, in the
      setting of structural inhomogeneities and unbalanced current source and load,
      decreased coupling can, at times, improve conduction and be 'anti-arrhythmic,'
      attesting to the complexity of intercellular coupling as a therapeutic target.
      Genetically engineered mouse models of Cx43 depletion demonstrate slow conduction
      and arrhythmogenesis that appears to be reentrant in nature. Studies in these
      models provide novel insights into the contribution of gap junctions to impulse
      propagation and arrhythmogenesis in the intact heart. Overall, gap junction
      expression, distribution and heterogeneity are important contributors to
      microscopic conduction, and alterations in any of these can contribute to the
      development of an arrhythmogenic substrate in pathological states.

PMID- 16646587
TI  - Pharmacology of cardiovascular gap junctions.
AB  - Gap junction (GJ) channels play an important role in forming a functional network
      or syncytium of cells by allowing the transfer of small molecules or the
      conduction of electrical activation. These channels can be regulated at the level
      of acute opening or closure as well as at the level of expression including
      synthesis, protein trafficking and degradation. Many of the underlying mechanisms
      depend on phosphorylation or dephosphorylation of connexins. A number of drugs is
      available to study GJ function and connexin expression. Some of these drugs have
      shown therapeutic effects, e.g. the anti-arrhythmic peptides AAP10 and ZP123 in
      the prevention of certain types of arrhythmia. Moreover, mediators involved in
      cardiovascular pathophysiology, e.g. angiotensin, endothelin, tumor necrosis
      factor-alpha, fibroblast growth factor and others, affect connexin expression and
      can alter the Cx43/Cx40 ratio, which may contribute to the formation of an
      arrhythmogenic substrate. On the other hand, drugs affecting these mediators may
      influence GJ networking and may thus open new therapeutic horizons.

PMID- 16646588
TI  - Structural and functional coupling of cardiac myocytes and fibroblasts.
AB  - Cardiac myocytes and fibroblasts form extensive networks in the heart, with
      numerous anatomical contacts between cells. Fibroblasts, obligatory components of
      the extracellular matrix, represent the majority of cells in the normal heart,
      and their number increases with aging and during disease. The myocyte network,
      coupled by gap junctions, is generally believed to be electrically isolated from
      fibroblasts in vivo. In culture, however, the heterogeneous cell types form
      functional gap junctions, which can provide a substrate for electrical coupling
      of distant myocytes, interconnected by fibroblasts only. Whether similar behavior
      occurs in vivo has been the subject of considerable debate. Recent
      electrophysiological, immunohistochemical, and dye-coupling data confirmed the
      presence of direct electrical coupling between the two cell types in normal
      cardiac tissue (sinoatrial node), and it has been suggested that similar
      interactions may occur in post-infarct scar tissue. Such heterogeneous cell
      coupling could have major implications on in vivo electrical impulse conduction
      and the transport of small molecules or ions in both the normal and pathological
      myocardium. This review illustrates that it would be wrong to adhere to a
      scenario of functional integration of the heart that does not allow for a
      potential active contribution of non-myocytes to cardiac electrophysiology, and
      proposes to focus further research on the relevance of non-myocytes for cardiac
      structure and function.

PMID- 16646589
TI  - Connexins and cardiac arrhythmias.
AB  - During cardiac remodeling, impulse conduction in the heart is altered by changes
      in excitability, electrical coupling, and tissue architecture. The impairment of
      normal impulse conduction is one of the factors that increases the propensity for
      arrhythmias. This chapter focuses on the relationship between electrical coupling
      between ventricular myocytes and arrhythmogenesis. Mouse models of decreased
      electrical coupling in the heart have shown that a clinically relevant 50%
      reduction in gap junctions in the heart has no effect on impulse conduction or
      arrhythmogenesis. To impair conduction and arrhythmias, coupling has to be
      reduced to very low levels. Apparently, there is a large conduction reserve,
      which can preserve normal impulse conduction even when electrical coupling is
      moderately reduced. However, cardiac remodeling is also associated with reduced
      excitability and increased levels of collagen deposition (fibrosis). It is
      therefore presumably the combination of, in itself ineffective, reduction of
      electrical coupling with other impairments like fibrosis or reduced excitability
      that causes the limits of conduction reserve to be exceeded, thereby resulting in
      abnormal impulse conduction and enhanced arrhythmogenesis.

PMID- 16646590
TI  - Role of connexins in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in humans. AF is
      accompanied by a remodeling process which changes the electrophysiology of the
      cells and the gap junctional communication within the tissue. Gap junctions,
      forming communicating channels between neighboring cells, and their specific
      geometric arrangement seem to contribute to the initiation of AF within the
      pulmonary veins as well as to the stabilization of AF providing a heterogeneous
      biophysical network of cells enabling multiple wavelets. These tissue changes are
      accompanied by fibrosis and changes in the expression levels of Cx43 and Cx40,
      probably depending on the underlying diseases or the animal model used. New
      studies point to a modulating role of angiotensin II in this process and a
      possible therapeutic role for ACE inhibitors or AT(1) antagonists.

PMID- 16646591
TI  - Connexins in the sinoatrial and atrioventricular nodes.
AB  - The sinoatrial node (SAN) and the atrioventricular node (AVN) are specialized
      tissues in the heart: the SAN is specialized for pacemaking (it is the pacemaker
      of the heart), whereas the AVN is specialized for slow conduction of the action
      potential (to introduce a delay between atrial and ventricular activation during
      the cardiac cycle). These functions have special requirements regarding
      electrical coupling and, therefore, expression of connexin isoforms. Electrical
      coupling in the center of the SAN should be weak to protect it from the
      inhibitory electrotonic influence of the more hyperpolarized non-pacemaking
      atrial muscle surrounding the SAN. However, for the SAN to be able to drive the
      atrial muscle, electrical coupling should be strong in the periphery of the SAN.
      Consistent with this, in the center of the SAN there is no expression of Cx43
      (the principal connexin of the working myocardium) and little expression of Cx40,
      but there is expression of Cx45 and Cx30.2, whereas in the periphery of the SAN
      Cx43 as well Cx45 is expressed. In the AVN, there is a similar pattern of
      expression of connexins as in the center of the SAN and this is likely to be in
      large part responsible for the slow conduction of the action potential.

PMID- 16646592
TI  - Cardiac ischemia and uncoupling: gap junctions in ischemia and infarction.
AB  - Acute cardiac ischemia is often associated with ventricular arrhythmia and
      fibrillation. Due to the loss of ATP, the depolarization of the fibers, and the
      intracellular Na(+) and Ca(2+) overload with concomitant acidification as well as
      the accumulation of lysophosphoglyceride and arachidonic acid metabolites,
      propagation of action potentials will be impaired by two factors: (a) reduced
      sodium channel availability and (b) gap junction uncoupling. While gap junction
      uncoupling leads to predominant transverse uncoupling, reduced I (Na)
      availability results in impaired longitudinal conduction. Complete gap junction
      uncoupling would initiate arrhythmia, while intermediate uncoupling has been
      shown to enhance the safety factor (SF) of propagation, limiting the current loss
      to non-depolarized areas. In contrast, a reduction in I(Na) availability reduces
      SF, and partial gap junction uncoupling might enable effective but slow
      conduction which, on the other hand, could form the basis for some kind of
      reentrant arrhythmia, paving the way for new anti-arrhythmic approaches in gap
      junction coupling. In the chronic phase, remodeling processes also involve gap
      junctions and lead to highly heterogeneous non-uniform tissue which may serve as
      an arrhythmogenic trigger.

PMID- 16646593
TI  - Connexin43 and ischemic preconditioning.
AB  - Connexin43 (Cx43) is the essential protein to form hemichannels and gap junctions
      in the myocardium. The phosphorylation status of Cx43 which is regulated by a
      variety of protein kinases and phosphatases determines hemichannel and/or gap
      junction conductance and permeability. Gap junctions are involved in cell-cell
      coupling while hemichannels contribute to cardiomyocyte volume regulation. Cx43
      formed channels are involved in ischemia/reperfusion injury, since blockade of a
      large portion of Cx43-formed channels attenuates ischemic hypercontracture,
      infarct development and post myocardial infarction remodeling. Ischemic
      preconditioning's protection also depends on functional Cx43-formed channels,
      since uncoupling of channels or genetic Cx43 deficiency abolishes infarct size
      reduction by ischemic preconditioning. The exact underlying mechanism(s) how Cx43
      mediates protection remain to be established.

PMID- 16646594
TI  - Alterations in cardiac connexin expression in cardiomyopathies.
AB  - Gap junctions, assembled from connexins, form the cell-to-cell pathways for
      propagation of the precisely orchestrated patterns of current flow that govern
      the synchronized rhythm of the healthy heart. As in most tissues and organs,
      multiple connexin types are co-expressed in the heart; the connexins Cx43, Cx40
      and Cx45 are found in distinctive combinations and relative quantities in
      different, functionally specialized subsets of cardiomyocytes. Alterations in
      connexin expression and gap junction organization, now a well-documented feature
      of human cardiomyopathies, potentially contribute to the pro-arrhythmic
      substrate. In the diseased ventricle, the most consistently reported quantitative
      alteration involves heterogeneous reduction in Cx43 expression and disruption of
      the normal ordered pattern of Cx43 gap junction distribution. Additional studies
      suggest that upregulation of Cx40 and Cx45 may also feature in the failing
      ventricle, the former restricted to ischemic cardiomyopathy and localized to the
      subendocardial region. By correlating data from studies on the human patient with
      those from animal and cell models, alterations in connexin expression and gap
      junction organization have emerged as important factors to be considered in
      understanding the pro-arrhythmic substrate found in human cardiomyopathies.

PMID- 16646595
TI  - Alterations of connexin 43 in the diabetic rat heart.
AB  - In the streptozotocin-induced diabetic rat heart, a decrease in the conductivity
      and suppression of electrical cell-to-cell coupling has been observed. To clarify
      this mechanism, the present study was performed to investigate the gap junction
      connexin 43 (Cx43) using immunohistochemistry, immunoblot, electron-microscopic
      analyses. Enhanced activation of PKCepsilon, augmentation of PKCepsilon-mediated
      phosphorylation of Cx43, a decrease in the total amount of Cx43, a reduction in
      the number of immunoreactive particles for Cx43 at the intercalated disk and
      internalization, annular profiles of the gap junction were all recognized in the
      diabetic heart. Such a deterioration in the expression of Cx43 was alleviated by
      treatment with either lysosomal (leupeptin) or proteasomal inhibitor (ALLN).
      These results suggest that the PKCepsilon-mediated hyperphosphorylation of Cx43
      makes Cx43 vulnerable to proteolytic degradation, while a decrease in the
      conductivity in the diabetic heart is also caused by a decrease in the number of
      gap junction channels due to an acceleration of the proteolytic degradation of
      Cx43. The remodeling of Cx43 induced by the activation of PKC may therefore
      contribute to the formation of the arrhythmogenic substrate.

PMID- 16646596
TI  - Connexins in atherosclerosis.
AB  - Remodeling of the vascular wall plays a central role in many physiological
      processes, but also in the pathogenesis of cardiovascular diseases such as
      atherosclerosis and restenosis. Atherosclerosis represents the major cause of
      death and disability in adult populations of Western societies. Angioplasty is a
      common and effective method of treatment for coronary atherosclerosis, but
      restenosis after the procedure continues to be a serious clinical complication.
      The development of atherosclerosis and restenosis involves complex patterns of
      interactions between the dysfunctional endothelium, inflammatory cells and smooth
      muscle cells in which cytokines and growth factors are known to play a critical
      role. Apart from paracrine cell-to-cell signaling, a role for gap-junction
      mediated intercellular communication has recently been suggested. In this
      chapter, we summarize existing evidence supporting such a role. Thus, the pattern
      of vascular connexins is altered during atherosclerotic plaque formation and in
      restenosis. In addition, disturbances in flow, inflammation and smooth muscle
      cell activation and proliferation have been shown to affect connexin expression
      or gap junctional communication. Finally, genetically modified connexin
      expression alters the course of these diseases in mice. Further studies will tell
      us whether future treatment of atherosclerosis or restenosis may involve connexin
      based strategies.

PMID- 16646597
TI  - Connexin-dependent communication within the vascular wall: contribution to the
      control of arteriolar diameter.
AB  - Communication between cells is important to the microcirculation and enables the
      coordination of cellular behavior along the length of the vessel. Arterioles span
      considerable distances within the microcirculatory network, and thus flow changes
      require the adaptation of vessel resistance over the whole length of the vessel
      in order to be effective. Such a task requires communication along the vessel
      wall, and gap junction channels that connect endothelial as well as smooth muscle
      cells with each other set the stage for this requirement. Communication along the
      vessel wall can be tested experimentally by confined local stimulation of
      arterioles either in vitro or in vivo. Certain vascular stimuli induce both a
      local response and a concomitant uniform remote response, confirming the rapid
      conduction of vasomotor stimuli along the vessel wall. Gap junctions in vascular
      tissue are composed of connexins (Cx) Cx40, Cx43, Cx37 and Cx45. Of these, Cx40
      is of special importance: its lack results in a deficient conduction of
      vasodilator stimuli along the vessel wall. Interestingly, Cx40-deficient mice
      display an elevated mean arterial pressure, suggesting that Cx40-depending gap
      junctional coupling is necessary to regulate vascular behavior and peripheral
      resistance. While the role of other connexins is less well established, an
      abundance of experimental data has proven the necessity of gap junctional
      communication to coordinate vascular behavior during adaptive blood flow
      regulation.

PMID- 16646598
TI  - Cx40 polymorphism in human atrial fibrillation.
AB  - Previous studies have shown that two linked polymorphisms within regulatory
      regions of the gene for connexin40 (Cx40), at nucleotides -44 (G --> A) and +71
      (A --> G) occur in about 7% of the general population. Cx40 is abundant in the
      atrium, and homozygosity for the linked polymorphisms combined with an SCN5A
      mutation appeared to be responsible for familial atrial standstill. We
      hypothesized that these polymorphisms are associated with the atrial
      electrophysiologic substrate favoring reentrant mechanisms for initiation of
      atrial fibrillation (AF). Reentry is promoted by spatial dispersion of
      refractoriness that can be expressed as a coefficient of dispersion (CD).
      METHODS: CD was calculated from the standard deviation of 12 local mean
      fibrillatory intervals recorded at right atrial sites during induced AF in 30
      patients without structural heart disease (14 sporadic AF episodes, 16 no AF
      history). CD <or= 3.0 was considered normal. Cx40 genotypes were determined by
      DNA sequencing. RESULTS: Mean CD in AF patients was 5.96 +/- 0.70 and without AF
      1.59 +/- 0.18 (p < 0.001). Thirteen of fourteen patients with AF had enhanced CD.
      Carriers of -44 AA genotype had higher CD compared with those with -44 GG
      genotype (6.37 +/- 1.21 vs. 2.38 +/- 0.39, p = 0.018), whereas heterozygotes
      showed intermediate values (3.95 +/- 1.38, NS). CONCLUSION: The rare linked Cx40
      polymorphisms are associated with enhanced CD and thus with the substrate for
      reentry in AF.

PMID- 16646600
TI  - Introduction to biostatistics: Part 3. Statistical approaches to uncertainty: P
      values and confidence intervals unpacked.

PMID- 16646601
TI  - Review: medical history, physical examination, and routine tests are useful for
      diagnosing heart failure in dyspnea.

PMID- 16646602
TI  - Review: antibiotic prophylaxis reduces mortality in patients with neutropenia
      after chemotherapy.

PMID- 16646603
TI  - Addition of clopidogrel to aspirin, but not early use of metoprolol, improved
      overall outcome in acute myocardial infarction.

PMID- 16646604
TI  - Rescue angioplasty reduced cardiovascular and cerebrovascular outcomes in acute
      MI after failed thrombolytic therapy.

PMID- 16646605
TI  - Review: evidence supporting reduced death and reinfarction by percutaneous
      coronary intervention after thrombolysis is inconclusive.

PMID- 16646606
TI  - Review: cholesterol-lowering treatment with statins reduces all-cause mortality
      in persons at risk.

PMID- 16646607
TI  - Intensive insulin therapy reduced cardiovascular disease in type 1 diabetes.

PMID- 16646609
TI  - Long-term fenofibrate therapy did not reduce major coronary events but may reduce
      total CVD events in type 2 diabetes mellitus.

PMID- 16646608
TI  - Review: angiotensin-converting enzyme inhibitors and angiotensin-receptor
      blockers prevent type 2 diabetes.

PMID- 16646610
TI  - Review: cardioselective beta-blockers do not produce adverse respiratory effects
      in COPD.

PMID- 16646611
TI  - Review: beta-blockers are less effective than other antihypertensive drugs for
      reducing risk for stroke in primary hypertension.

PMID- 16646612
TI  - A nonselective beta-blocker did not prevent gastroesophageal varices in cirrhosis
      and portal hypertension.

PMID- 16646613
TI  - Bypass surgery and balloon angioplasty did not differ for amputation-free
      survival in severe limb ischemia.

PMID- 16646614
TI  - Review: a pulmonary artery catheter does not reduce mortality or hospital days in
      critically ill patients.

PMID- 16646615
TI  - Low-dose iron supplementation was effective in older patients with iron
      deficiency anemia.

PMID- 16646616
TI  - Initial combination therapy with prednisone or infliximab improved outcomes in
      early rheumatoid arthritis more than DMARDs alone.

PMID- 16646617
TI  - Prednisolone plus a disease-modifying antirheumatic drug improved outcomes in
      early rheumatoid arthritis.

PMID- 16646618
TI  - Oral mycophenolate led to more complete remissions than intravenous
      cyclophosphamide for active lupus nephritis.

PMID- 16646619
TI  - Oral contraceptives did not increase risk for flare in women with systemic lupus
      erythematosus.

PMID- 16646620
TI  - Review: capsule endoscopy has high yield for small bowel findings in obscure
      gastrointestinal bleeding.

PMID- 16646621
TI  - Family history and dysplastic nevi increased risk for multiple primary melanomas
      after an initial melanoma.

PMID- 16646622
TI  - Being overweight or obese was associated with a greater risk for end-stage renal
      disease.

PMID- 16646623
TI  - Review: care assisted by nurses or pharmacists provides better blood pressure
      control.

PMID- 16646624
TI  - Moderate- and high-intensity implementation of guidelines increased outpatient
      care of low-risk pneumonia.

PMID- 16646625
TI  - A clinical decision support system reduced antimicrobial use for acute
      respiratory tract infections in rural settings.

PMID- 16646626
TI  - Trauma-induced systemic inflammatory response versus exercise-induced
      immunomodulatory effects.
AB  - Accidental trauma and heavy endurance exercise, both induce a kind of systemic
      inflammatory response, also called systemic inflammatory response syndrome
      (SIRS). Exercise-related SIRS is conditioned by hyperthermia and concomitant heat
      shock responses, whereas trauma-induced SIRS manifests concomitantly with tissue
      necrosis and immune activation, secondarily followed by fever. Inflammatory
      cytokines are common denominators in both trauma and exercise, although there are
      marked quantitative differences. Different anti-inflammatory cytokines may be
      involved in the control of inflammation in trauma- and exercise-induced stress.
      Exercise leads to a balanced equilibrium between inflammatory and anti
      inflammatory responses. Intermittent states of rest, as well as anti-oxidant
      capacity, are lacking or minor in trauma but are high in exercising individuals.
      Regular training may enhance immune competence, whereas trauma-induced SIRS often
      paves the way for infectious complications, such as sepsis.

PMID- 16646627
TI  - Gastroesophageal reflux disease and physical activity.
AB  - Gastroesophageal reflux disease (GERD) is one of the most common disorders in the
      general population. In recent years, a marked increase in the occurrence of the
      disease worldwide has been noted. Intense exercise belongs to factors that are
      known to exacerbate symptoms of GERD. Episodes of reflux seem to be associated
      with the length and the intensity of the physical activity undertaken.
      Experimental studies suggest that the gastroesophageal reflux may be increased in
      athletes due to: decreased gastrointestinal blood flow; alterations of hormone
      secretion; changes in the motor function of the oesophagus and the ventricle; and
      the constrained body position during exercise. Disturbances of the balance
      between two areas of opposite pressure: intra-abdominal and intrathoracic, have
      also been proven to influence GERD events. GERD is found in sportspeople of
      various disciplines, but specific types of exercise may have significantly
      different impacts on the gastroesophageal reflux.Basic prevention of GERD
      comprise lifestyle and dietary interventions. Adjustments of the exercise load
      and avoiding meals and drinks about the time of physical effort may ease the
      symptoms. Unfortunately, in most patients, pharmacological measures are
      necessary. These include occasional application of antacids and blockers of
      histamine H2 receptors in mild forms of the disease, and a regular therapy with
      proton pump inhibitors (PPI) in the majority of other cases. An average dose of
      PPI varies from 20 to 40 mg/day and should be continued for 4-8 weeks.
      Unfortunately, symptoms of GERD frequently return and in these situations long
      term acid suppression with PPI is usually necessary. As regular physical activity
      exerts beneficial health effects, the necessity of establishing associations
      between moderate, recreational exercise and GERD is needed.

PMID- 16646628
TI  - Measurement and evaluation of dynamic joint stability of the knee and ankle after
      injury.
AB  - Injuries to the lower extremity, specifically the knee and ankle joints of the
      human body can occur in any athletic event and are most prevalent in sports
      requiring cutting and jumping manoeuvres. These joints are forced to rely on the
      dynamic restraints to maintain joint stability, due to the lack of bony
      congruence and the inability of the static restraints to handle the forces
      generated during functional tasks. Numerous variables (proprioception, postural
      control, electromyography, kinetics/kinematics, dynamic stability protocols) have
      been measured to better understand how the body maintains joint stability during
      a wide range of activities from static standing to dynamic cutting or landing
      from a jump. While the importance of dynamic restraints is not questioned, a
      recent impetus to conduct more functional or sport-specific testing has emerged
      and placed a great deal of emphasis on dynamic joint stability and how it is
      affected by lower extremity injuries. Evidence suggests that surgery and
      aggressive rehabilitation will not necessarily restore the deficits in dynamic
      joint stability caused by injury to the anterior cruciate ligament or lateral
      ankle ligaments. In today's athletic society, there is a major push to return
      athletes to play as quickly as possible. However, the ramifications of those
      decisions have not been fully grasped. If an athlete is not fully recovered, a
      quick return to play could start a vicious cycle of chronic injuries or permanent
      disability.

PMID- 16646629
TI  - A risk-factor model for anterior cruciate ligament injury.
AB  - The incidence of non-contact anterior cruciate ligament (ACL) injury is reported
      to be 6-8 times greater in females than males competing in the same activities.
      Injury to the ACL occurs as a result of insufficient stability of the
      tibiofemoral joint, which fails to prevent posterior dislocation of the femur on
      the tibia. The stability of the tibiofemoral joint is maintained by passive (non
      contractile) and dynamic (contractile) mechanisms. The passive mechanisms include
      the shape of the articular surfaces, the menisci, the ligaments and the joint
      capsule. The dynamic mechanisms consist of the muscle-tendon units that cross the
      joint, in particular, the quadriceps and hamstrings. The relative significance of
      the various passive and dynamic mechanisms in maintaining the stability of the
      tibiofemoral joint is not clear. A number of intrinsic and extrinsic risk factors
      have been proposed to account for the sex difference in the incidence of ACL
      injuries. However, most of the proposed risk factors have arisen from univariate
      correlation studies based on relatively small samples.

PMID- 16646630
TI  - Ultra-endurance exercise and oxidative damage : implications for cardiovascular
      health.
AB  - At least 30 minutes of moderate-intensity physical activity accumulated on most,
      preferably all days is considered the minimum level necessary to reduce the risk
      of developing cardiovascular disease. Despite an unclear explanation, some
      epidemiological data paradoxically suggest that a very high volume of exercise is
      associated with a decrease in cardiovascular health. Although ultra-endurance
      exercise training has been shown to increase antioxidant defences (and therefore
      confer a protective effect against oxidative stress), an increase in oxidative
      stress may contribute to the development of atherosclerosis via oxidative
      modification of low-density lipoprotein (LDL). Research has also shown that ultra
      endurance exercise is associated with acute cardiac dysfunction and injury, and
      these may also be related to an increase in free radical production. Longitudinal
      studies are needed to assess whether antioxidant defences are adequate to prevent
      LDL oxidation that may occur as a result of increased free radical production
      during very high volumes of exercise. In addition, this work will assist in
      understanding the accrued effect of repeated ultra-endurance exercise-induced
      myocardial damage.

PMID- 16646631
TI  - Physical activity and high-sensitivity C-reactive protein.
AB  - Cardiovascular disease (CVD) remains one of the leading causes of death and
      disability in developed countries around the world despite the documented success
      of lifestyle and pharmacological interventions. This illustrates the
      multifactorial nature of atherosclerosis and the use of novel inflammatory
      markers as an adjunct to risk factor reduction strategies. As evidence continues
      to accumulate that inflammation is involved in all stages of the development and
      progression of atherosclerosis, markers of inflammation such as high-sensitivity
      C-reactive protein (CRP) may provide additional information regarding the
      biological status of the atherosclerotic lesion. Recent investigations suggest
      that physical activity reduces CRP levels. Higher levels of physical activity and
      cardiorespiratory fitness are consistently associated with 6-35% lower CRP
      levels. Longitudinal training studies that have demonstrated reductions in CRP
      concentrations range from 16% to 41%, an effect that may be independent of
      baseline levels of CRP, body composition or weight loss. The average change in
      CRP associated with physical activity appears to be at least as good, if not
      better, than currently prescribed pharmacological interventions in similar
      populations. The primary purpose of this review will be to present evidence from
      both cross-sectional and longitudinal investigations that physical activity
      lowers CRP levels in a dose-response manner. Finally, this review will examine
      factors such as body composition, sex, blood sample timing, diet and smoking,
      which may influence the CRP response to physical activity.

PMID- 16646632
TI  - Crystal structure of the HSV-1 Fc receptor bound to Fc reveals a mechanism for
      antibody bipolar bridging.
AB  - Herpes simplex virus type-1 expresses a heterodimeric Fc receptor, gE-gI, on the
      surfaces of virions and infected cells that binds the Fc region of host
      immunoglobulin G and is implicated in the cell-to-cell spread of virus. gE-gI
      binds immunoglobulin G at the basic pH of the cell surface and releases it at the
      acidic pH of lysosomes, consistent with a role in facilitating the degradation of
      antiviral antibodies. Here we identify the C-terminal domain of the gE ectodomain
      (CgE) as the minimal Fc-binding domain and present a 1.78-angstroms CgE
      structure. A 5-angstroms gE-gI/Fc crystal structure, which was independently
      verified by a theoretical prediction method, reveals that CgE binds Fc at the
      C(H)2-C(H)3 interface, the binding site for several mammalian and bacterial Fc
      binding proteins. The structure identifies interface histidines that may confer
      pH-dependent binding and regions of CgE implicated in cell-to-cell spread of
      virus. The ternary organization of the gE-gI/Fc complex is compatible with
      antibody bipolar bridging, which can interfere with the antiviral immune
      response.

PMID- 16646633
TI  - Trends in suicidology: personality as an endophenotype for molecular genetic
      investigations.

PMID- 16646634
TI  - Promoting regional health cooperation: the South Asian Public Health Forum.

PMID- 16646635
TI  - Does alpha+-thalassaemia protect against malaria?

PMID- 16646636
TI  - Gallinyalla: a town of substance? A descriptive study of alcohol, tobacco,
      medicines and other drug use in a rural setting.
AB  - INTRODUCTION: This study investigates substance use in a regional town in South
      Australia. METHODS: The study objectives were to identify Aboriginal and non
      Aboriginal views on and individual practices in substance use, and its impact on
      the community. Working together, Aboriginal and non-Aboriginal community members
      identified the scope of the issue of substance use using four broad questions,
      and where solutions might lie. Individuals also reported their personal substance
      use. Qualitative methods involving 24 focus groups (n = 211) and 285 key
      informant interviews (Aboriginal n = 160, non-Aboriginal n = 125) were used to
      obtain the data. Quantitative data were generated from structured elements of the
      key informant interviews. RESULTS: Alcohol was the main substance of concern,
      especially among young people. High marijuana use was also identified. The
      contribution of substance use to relationship breakdown and the impact this has
      on families and the community was an important theme. There was agreement on the
      need for broad community strategies to link and strengthen agencies that deal
      with substance use issues in Gallinyalla, and to promote the reconciliation
      process. CONCLUSION: The implications for policy and practice from this project
      support the need for substance use strategies in which the community plays a
      major role.

PMID- 16646637
TI  - Dental self-care and dietary characteristics of remote-living Indigenous
      children.
AB  - INTRODUCTION: Indigenous children in remote communities carry a disproportionate
      amount of the dental disease burden among Australian 4-12 year-olds. However,
      there have been no reports of dental service use, dental self-care or dietary
      characteristics among remote-living Indigenous children. This information may
      provide insight into behaviours linked with the high levels of dental disease
      observed. The purpose of this study was to examine such behaviours among
      Indigenous children in three remote communities in the Top End of the Northern
      Territory of Australia. The study is part of a wider investigation involving the
      implementation and monitoring of water fluoridation plants in two of the
      communities, and the collection of clinical dental data from children in these
      three and other remote communities. METHODS: In 2003, small-scale fluoridation
      plants were installed in two remote communities (Communities A and B) in the Top
      End of the Northern Territory with naturally low fluoride levels in the water and
      with a high prevalence of child dental disease. Another community (Community C)
      was selected as a comparison site (natural levels of water fluoride low). A
      convenience sample of carers of children from all communities completed a
      questionnaire that sought information on carer education and their children's
      age, sex, use of dental services, dental self-care behaviours, dietary
      characteristics, household water source and water consumption. The questionnaires
      were administered by a project worker and community residents once consent had
      been obtained. Data were analysed using SPSS version vers.13.0 (SPSS Inc;
      Chicago, IL, USA). RESULTS: Some 214 carers completed the questionnaire for 409
      children aged 4-12 years; 131 (32.0%) from Community A, 158 (38.6%) from
      Community B and 120 (29.3%) from Community C. The response rates for the child
      survey based on Census data (generally regarded as an undercount) was 55% across
      the three communities. Approximately one-third of carers had had no secondary
      schooling or could not recall their level of educational attainment. Child age
      was reasonably spread over the target age-range and there were no significant
      differences between communities by sex. Approximately one-third of children were
      reported to have had their teeth checked every year by a dental therapist and
      most children were reported to use a toothbrush. While most children were also
      reported to use toothpaste, only 20% of such children reportedly used it every
      day. Time of toothpaste use was evenly distributed between morning and evening,
      with a small proportion of children reportedly using it twice a day. The most
      common age that toothpaste use began was 4 years and most children had never
      taken fluoride supplements. Over three-quarters of children who reportedly
      consumed softdrinks, cordial, milk or flavoured milk in the evenings drank such
      beverages at least a few evenings each week. Over 90% of children across the
      three communities who reportedly drank tea, and approximately three-quarters of
      those who consumed sweet snacks, did so at least a few evenings each week. Almost
      all houses were connected to the community water supply. Most children sourced
      their drinking water from a tap and approximately two-thirds were reported to
      drink more than 4 cups of water a day. CONCLUSIONS: Our study showed there were
      low levels of preventive dental care, irregular use of dentrifices, negligible
      implementation of alternative fluoride sources, high consumption of sweetened
      snacks and drinks in the evenings, and almost universal connection of houses to
      the public water supply among remote-dwelling Indigenous children. The findings
      provide some insights into factors contributing to the poor and declining state
      of such children's dental health, and should aid in the planning and
      implementation of oral health promotion initiatives.

PMID- 16646639
TI  - SEM-morphology in dentinogenesis imperfecta type II: microscopic anatomy and
      efficacy of a dentine bonding system.
AB  - AIM: Dentinogenesis Imperfecta is a hereditary defect consisting of opalescent
      teeth composed of irregularly formed and undermineralised dentin that obliterates
      the coronal and root pulpal chambers. The aim of this study was to examine the
      morphology of permanent human enamel, dentine and the dentine-enamel junction, in
      individuals affected by Dentinogenesis Imperfecta type II in undercalcified
      sections using scanning electron microscope (SEM) to compare the findings to the
      normal morphology, and to study the efficacy of modern bonding system to dentine
      and enamel DI type II affected. MATERIALS AND METHODS: Four third molars
      extracted from two 19 year-old subjects (one patient affected by Dentinogenesis
      Imperfecta type II) were included in resin, two divided in slices with a air
      cooled diamond disc, and two used to study the characterisation of the resin
      dentin interface. The sections of the teeth were examined by means of SEM. The
      slices were finished up with abrasive paper (400, 600, 1000, and 2000), the half
      surfaces obtained were etched with 37% phosphoric acid and then joined up to the
      stubs for SEM analysis. SEM Stereoscan 440 Leica with magnifications of 20X,
      100X, 250X, 1000X, 2000X, 3000X was used. As control group were used four third
      molars with normal anatomy. RESULTS: This study shows that the permanent enamel
      from patients with DI exhibits few structural changes. No relationships were
      found between enamel morphology and the DI type II. Enamel appeared to be
      regularly mineralised. The major findings were anomalies in the dentine-enamel
      junction, locally a lower degree of mineralisation and an undulating morphology.
      The dentine showed absence of tubules. CONCLUSION: This study confirms that the
      problem with teeth affected by DI type II is the defect in dentine and weakness
      in the way the enamel is attached to the dentine. The adhesive system tested is
      not able to create a real hybrid layer in dentine DI type II affected and seems
      to be less effective than on normal substrates.

PMID- 16646640
TI  - Visual input effect on EMG activity of masticatory and postural muscles in
      healthy and in myopic children.
AB  - AIM: The purpose of this study was to evaluate the activity of Anterior Temporal,
      Masseter, Sternocleidomastoid and Anterior Digastric muscles in response to
      changes in visual input in subjects with defective vision by means surface
      electromyography. METHODS: A total of 20 children, aged between 7 and 13 years,
      were evaluated. In the study group 10 children with myopic defects were enlisted,
      selected among patients afferent to the paediatric dentistry clinic. Ten subjects
      with normal vision, the control group, were chosen through the Pair Matching
      procedures, so that each myopic child had a matching age case control. Both study
      group and control group patients maintained mandible at rest with teeth apart and
      were submitted to a 15-sec electromyography (EMG) recording with closed eyes
      followed by a 15-sec EMG recording with open eyes. RESULTS/STATISTICS: The Root
      Mean Square (RMS) values were elaborated to obtain means and standard deviation.
      Statistical analysis was undertaken using the Student's T-test for independent
      samples. Analysis of the results demonstrated a marked difference in tonic
      activity of temporal anterior muscles at open eyes between the myopic and the
      normal groups. CONCLUSION: The findings suggest that in the evaluation of
      masticatory muscles tenderness, such as episodic tension type headaches,
      attention should be paid to vision defects.

PMID- 16646641
TI  - Class III dento-skeletal anomalies: rotational growth and treatment timing.
AB  - AIM: The interception of a Class III malocclusion requires a long-term growth
      prediction in order to estimate the subject's evolution from the prepubertal
      phase to adulthood. The aim of this retrospective longitudinal study was to
      highlight the differences in facial morphology in relation to the direction of
      mandibular growth in a sample of subjects with Class III skeletal anomalies
      divided on the basis of their Petrovic's auxological categories and rotational
      types. MATERIALS AND METHODS: The study involved 20 patients (11 females and 9
      males) who started therapy before reaching their pubertal peak and were followed
      up for a mean of 4.3 years (range: 3.9-5.5 years). RESULTS: Despite the small
      sample size, the definition of the rotational type of growth was the main
      diagnostic element for setting the correct individualised therapy. CONCLUSION: We
      therefore believe that the observation of a larger sample would reinforce the
      diagnostic-therapeutic validity of Petrovic's auxological categories, allow an
      evaluation off all rotational types, and improve the statistical significance of
      the results obtained.

PMID- 16646642
TI  - Radiographic appearance of apical closure in apexification: follow-up after 7-13
      years.
AB  - AIM: This was the radiographic evaluation of 15 maxillary incisors apexification
      treatment carried out on 7-9 years old patients with periapical pathology due to
      pulpal necrosis after dental trauma. MATERIALS AND METHODS: The treatment
      consisted of two phases. The aim of first phase was the formation of a calcified
      apical barrier through calcium hydroxide medications repeated twice with a three
      months interval. The aim of the second phase was the obturation of the root canal
      system once achieved a radiographic evidence of the formation of an apical
      barrier. The treated teeth were radiographed at six months and then periodically
      once a year for a period of 7 and 13 years. RESULTS: The radiographic analysis
      allowed to underline three different kinds of apical formation: a physiological
      development of the apical portion with a final root length equal to the
      contralateral tooth; the formation of a cap tissue and an apical development with
      the final root length slightly shorter than the contralateral tooth; or the
      formation of different layers of mineralised tissue that aggregate together
      trough the years. CONCLUSION: Apexification is not a static phenomenon and the
      apexified area undergoes through the years to a conspicuous readjustment
      involving bone, apical root tissues and root filling material.

PMID- 16646643
TI  - Effectiveness of oral hygiene protocol in patients with post-traumatic splinting.
AB  - AIM: In dental trauma with severe periodontal tissue involvement, as dental
      avulsion and severe luxation, the splinting procedure requires the patient to
      maintain a scrupulous hygiene of the affected zone, so to allow an effective
      tissue healing. The aim of this study was to assess the effectiveness of a
      specific oral hygiene protocol in the treatment of patients with post-traumatic
      splinting, comparing the plaque indexes of dental hygienist-helped patients
      versus not helped. MATERIALS AND METHODS: This study was carried out on 82
      selected patients with post-traumatic splinting due to traumatic avulsion and
      severe luxation. They were divided into 2 groups, comparable for age, sex, type
      of trauma and splinting. The group A patients underwent an oral hygiene protocol,
      managed by a dental hygienist, while the group B patients were followed without
      the help of the hygienist. Plaque indexes were observed and compared in all cases
      during 6 weeks-follow up. RESULTS: Our results showed that at the 6th week follow
      up the plaque indexes of dental hygienist-assisted traumatized patients were
      significantly (p=0.001) lower than those of not assisted patients. CONCLUSION:
      Therefore, the role of dental hygienists is essential in the management of dental
      trauma with periodontal damage, which needs specific oral hygiene protocols.

PMID- 16646644
TI  - Malignant infantile osteopetrosis: dental effects in paediatric patients. Case
      reports.
AB  - AIM: Malignant Infantile Osteopetrosis is a hereditary pathology caused due to
      osteoclastic cells which are incapable of carrying out their functions and hence
      do not resorb osseous tissue where required. Thus the consequence is that during
      growth phase, the medullary cavities and nervous tissue cavities do not undergo
      sufficient growth and the corresponding organs do not develop adequately. The aim
      of this study is to outline the role of the pediatric dentist who has to carry
      out protocols of primary, secondary, tertiary prevention intervening at many
      levels. Clinical features and dental effects are described. Two case reports are
      presented in this study. CONCLUSION: Oral problems of osteopetrosis are delayed
      tooth eruption, absence of some teeth, malformed teeth, enamel hypoplasia,
      disturbed dentinogenesis, hypomineralisation of enamel and dentin, propensity for
      tooth decay, defects of the periodontal membrane, thickened lamina dura,
      mandibular protrusion, and the presence of odontomas. Tooth removal should be
      limited as it may induce bone fractures and osteomyelitis. The role of the
      pediatric dentist is defined.

PMID- 16646645
TI  - Supernumerary teeth and mental retardation: the importance of early surgical
      intervention.
AB  - AIM: This paper reported a rare case of hyperdontia in a child of 10 years who
      revealed a mixed dentition and a light mental retardation. MATERIALS AND METHODS:
      The therapeutic approach has been based on interdisciplinary cooperation between
      the pediatric dentist, orthodontist and oral surgeon. TC-Dentascan, with a
      panoramic and occlusal radiographs revealed the presence of two supernumerary
      teeth in the premaxillary region and clinical examination showed an abnormality
      of dentoalveolar complex. Both impacted supernumerary teeth were extracted under
      general anesthesia. Clinical examination revealed that they appeared two
      premolars in shape with fully formed crowns and partly formed roots. RESULTS:
      Three months after the extraction of supernumerary teeth there was a spontaneous
      eruption of permanent central incisors and left lateral incisor. CONCLUSION: The
      authors emphasized the importance of removal of supernumerary teeth to eliminate
      the cause of a delayed eruption of permanent teeth.

PMID- 16646646
TI  - Robot-assisted laparoscopic radical cystoprostatectomy and totally intracorporeal
      ileal neobladder.
AB  - PURPOSE: To describe robot-assisted laparoscopic radical cystoprostatectomy and
      intracorporeal orthotopic ileal neobladder construction. METHODS: With the use of
      the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA), we performed
      laparoscopic radical cystectomy and intracorporeal construction of an orthotopic
      ileal neobladder (modified W pouch). RESULTS: The total operative time was 12
      hours, and the estimated blood loss was 100 mL. There were no intraoperative or
      postoperative complications, and the patient?s hospital stay was 5 days. At early
      follow-up, oncologic and functional results are good. CONCLUSION: Robot-assisted
      laparoscopic radical cystoprostatectomy with intracorporeal ileal neobladder
      construction is technically feasible. However, its role in the management of
      invasive bladder cancer remains to be defined.

PMID- 16646647
TI  - Laparoscopic repair of external iliac-artery transection during laparoscopic
      radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: Vascular injuries are the most common complication of
      pelvic lymph-node dissection. We report a case of total division of the external
      iliac artery and its immediate laparoscopic repair. METHODS: A 70-year-old man
      with a prostatic adenocarcinoma (Gleason Score 6) and serum prostate specific
      antigen concentration of 20 ng/mL had inadvertent external iliac-artery
      transection during pelvic lymphnode dissection secondary to the abnormal course
      and anatomy of the artery. Immediate laparoscopic repair was accomplished with a
      two-needle single-knot technique as is routinely used for the vesicourethral
      anastomosis. Thereafter, laparoscopic radical prostatectomy was completed.
      RESULTS: The reconstruction time was 37 minutes. There was no significant blood
      loss. There were no further intraoperative complications. Postrepair, the femoral
      pulse was intact, and follow-up duplex color ultrasonography showed good flow.
      The patient was disharged home on day 7, ambulant and asymptomatic. CONCLUSION:
      In controlled cicumstances, laparoscopic repair of external iliac-artery
      transection is feasible and represents a safe alternative to open surgery.

PMID- 16646648
TI  - Laparoscopic transabdominal transvesical vesicovaginal fistula repair.
AB  - BACKGROUND AND PURPOSE: Transabdominal transvesical repair has been the standard
      treatment for difficult vesicovaginal fistulae. We describe a laparoscopic
      transvesical technique that minimizes operative morbidity while adhering to the
      principles of transabdominal repair as described by O'Conner. TECHNIQUE: The
      patient is placed in the lithotomy position using Allen stirrups, and bilateral
      5F open-ended ureteral catheters are placed cystoscopically. Using four
      laparoscopic ports, the prevesical space is accessed. The bladder is bivalved
      down to the fistula, and stay sutures are placed at the bladder edges for
      exposure. The fistulous tract and adjacent fibrotic tissue are excised, and the
      bladder and vagina are closed separately with single layers of full-thickness
      interrupted 2-0 Vicryl sutures. An omental flap is interposed between suture
      lines in the bladder and vagina. The ureteral catheters are sequentially removed
      on the first and second postoperative days. A gravity cystogram is performed 3
      weeks postoperatively; if it is normal, the urethral catheter is removed.
      RESULTS: This procedure has been performed on two consecutive patients who had
      failed prior Latzko repairs. Both patients were discharged 2 days postoperatively
      without complications. At a follow-up of 41 months in the first patient and 39
      months in the second, no fistula recurrence has been seen. CONCLUSIONS:
      Laparoscopic transvesical vesicovaginal fistula repair appears to be a safe and
      effective procedure that adheres to the principles of a transabdominal
      transvesical fistula repair while decreasing morbidity and improving cosmesis.
      Continued follow-up is required to determine its long-term efficacy compared with
      the accepted open transabdominal and transvaginal approaches.

PMID- 16646649
TI  - Bipolar transurethral resection of prostate in saline: preliminary report on
      clinical efficacy and safety at 1 year.
AB  - PURPOSE: To determine the clinical efficacy and safety profile of the bipolar
      transurethral resection in saline (TURIS) system (Olympus Japan) in the treatment
      of men with benign prostate hyperplasia (BPH). PATIENTS AND METHODS: We
      prospectively evaluated 45 patients with a mean age of 66 years (range 50-87
      years) who had clinically significant BPH and were treated with transurethral
      resection of prostate using the TURIS system beginning December 2003. Acute
      retention of urine was the indication in 49% of the patients. Patients had
      outpatient follow-ups at 1, 3, 6, and 12 months. RESULTS: A mean weight of 25.3 g
      of prostatic tissue was resected in a mean time of 42 minutes (range 15-75
      minutes). The mean decrease in hemoglobin and sodium was 1.4 g/dL and 2.2 mmol/L,
      respectively. The mean follow-up period was 10 months. The mean International
      Prostate Symptom Score decreased from 22.6 preoperatively to 6.5 at 12 months and
      the mean Q(max) increased from 6.5 to 18.3 mL/sec at 12 months. Postoperative
      hemorrhage was seen in 6.6% of the patients, including 2 primary hemorrhages that
      necessitated blood transfusion (4.4%). Other complications were prolonged
      catheterization (11.1%), urinary-tract infection (8.9%), and bulbar urethral
      stricture (4.4%). CONCLUSIONS: This pilot study indicates that TURIS is a safe
      and efficacious treatment for BPH at 1 year.

PMID- 16646650
TI  - Lower-caliceal stone clearance index to predict clearance of stone after SWL.
AB  - BACKGROUND AND PURPOSE: There is no uniform consensus regarding the anatomic
      factors that influence the clearance rate of caliceal stones after SWL, as
      different authors have studied various independent factors separately. We
      correlated both favorable and unfavorable factors into a formula to predict the
      clearance rate. PATIENTS AND METHODS: A series of 56 consecutive patients (37
      male, 19 female) with isolated lower-caliceal single stones (right 29, left 27)
      treated with SWL using the Dornier Compact Delta lithotripter were analyzed
      retrospectively. Of these, 40 patients had soft stones, and 16 patients had hard
      stones. The first stone-free rate (SFR) according to plain films and
      ultrasonography was analyzed by stone size, and a stone clearance index (SCI)
      formula was applied to see if there was any change in the SFR, especially for
      stones >2 cm. RESULTS: The formula, which correlated well with the clearance, is
      SCI = [(IVA x IW x stone type)/IH] - (stone size in mm(2)/10). Nearly all (90%)
      of the patients with an SCI of >0 cleared their stones within 3 months, and 87%
      of the patients with an SCI <0 cleared their stones after 3 months. Positive and
      negative predictive values were 93.33% and 76.9%, respectively. The accuracy of
      the correlation is 85.71%. CONCLUSIONS: The success of SWL for lower-caliceal
      stones can be predicted easily using the SCI. Stones of >200 mm(2) (>2 cm)
      surface area may still be suitable for SWL if the SCI is positive, whereas
      alternative treatment modalities should be considered if the SCI is a low
      negative value (<-7).

PMID- 16646651
TI  - Safety and outcome of rigid ureteroscopy for management of ureteral calculi in
      children.
AB  - PURPOSE: To present our experience with ureteroscopy for the treatment of
      pediatric ureteral calculi. PATIENTS AND METHODS: The records of 32 children with
      an average age of 8.7 years (range 2-15 years) treated with rigid ureteroscopy
      between June 1994 and July 2003 were reviewed. In 33 ureteral units, 8F rigid
      ureteroscopy was carried out 35 times to treat stone disease. Stones were located
      in the upper ureter in 2 cases, the middle ureter in 2 cases, and the lower
      ureter in 29 cases. Stone size ranged from 4 to 15 mm (mean 7 mm). Dilatation of
      the ureteral orifice was necessary in 10 procedures. RESULTS: The management of
      stone in 29 children (90.7%) was straightforward, and a single procedure was
      sufficient to clear the ureters. In 2 children (6.2%), repeat ureteroscopy was
      undertaken to render the ureters stone free, and in 1 child (3.1%), it was not
      possible to remove the stone. Stones were fragmented with pneumatic lithotripsy
      in 2 cases and with the holmium laser in 9; in the remaining 22 cases, the stones
      were removed without fragmentation. Intraoperative complications occurred in 3
      children (9.3%) and consisted of extravasation (1 patient) and stone migration (2
      patients). The early postoperative complications were hematuria in one patient
      and renal colic in another. Of the patients, 28 were followed 3 to 48 months. No
      stricture was detected at the site of stone impaction in any patient. CONCLUSION:
      In the hands of an experienced surgeon, ureteroscopy can be a safe and efficient
      treatment for ureteral stones in children.

PMID- 16646652
TI  - Fluoroscopy-assisted retroperitoneal laparoscopic renal surgery in children.
AB  - PURPOSE: To investigate the use of C-arm fluoroscopy for locating small
      dysplastic renal lesions during retroperitoneal laparoscopic nephrectomy in
      children. PATIENTS AND METHODS: From March 2003 to March 2005, two boys and four
      girls with a mean age of 5 years underwent retroperitoneal laparoscopic
      nephrectomy under C-arm fluoroscopic guidance. The indications for laparoscopic
      renal surgery were ectopic ureter with dysplastic kidney (N = 3), hypertensive
      nephropathy (N = 1), and dysplastic kidney secondary to reflux nephropathy (N =
      2). RESULTS: All operations were completed with no necessity for conversion to
      open surgery. Small dysplastic kidneys were easily located using C-arm
      fluoroscopy, and retroperitoneal laparoscopic nephrectomy was then performed. One
      patient required open contralateral reimplantation after laparoscopic nephrectomy
      because of high-grade vesicoureteral reflux. The mean operative time was 139
      minutes (range 71-210 minutes). Blood loss was minimal, and no transfusion was
      required. There were no intraoperative or postoperative complications other than
      a peritoneal injury in one patient, which caused no subsequent major problem. The
      mean postoperative hospital stay was 3.8 days, and all children returned to
      normal activity within 3 to 6 days. CONCLUSIONS: This is the first report to our
      knowledge of retroperitoneal laparoscopic renal surgery under C-arm fluoroscopic
      guidance. This approach allowed quick and easy location of small ectopic kidneys
      prior to retroperitoneal laparoscopic nephrectomy and was found to be very useful
      for the treatment of small dysplastic renal lesions in children.

PMID- 16646653
TI  - Case report: laparoscopic repair of saccular renal-artery aneurysm.
AB  - We report successful laparoscopic repair of a saccular renal-artery aneurysm in a
      patient with renovascular hypertension. The repair was performed by clamping the
      renal hilum, excising the aneurysm, and suturing the vascular defect
      intracorporeally. Postoperative imaging studies confirmed normal arterial flow in
      the repaired artery.

PMID- 16646654
TI  - Laparoscopic adrenalectomy for primary hyperaldosteronism: clinical experience
      with 60 cases.
AB  - PURPOSE: To assess the long-term outcome of patients with primary
      hyperaldosteronism who underwent laparoscopic adrenalectomy and to study hormone
      dynamics and differences between postoperative and preoperative blood pressure.
      PATIENTS AND METHODS: From December 1992 to February 2005, 60 patients with
      primary hyperaldosteronism underwent laparoscopic adrenalectomy at our
      institution. Their clinical and biochemical parameters were reviewed
      retrospectively. In 45 patients, it was possible to follow the hormone dynamics
      and blood pressure to compare the preoperative values with those >or=2 months
      after the operation. RESULTS: The average operating time was 261.7 minutes (range
      95-835 minutes), and the average blood loss was 204.2 mL (range 10-3740 mL). The
      average time to ambulation was 1.7 days (range 1-7 days). Five patients (8.3%)
      had intraoperative hemorrhage that necessitated blood transfusion. Serum
      aldosterone in all 45 patients who were followed up was normalized
      postoperatively. At >or=2 months postoperatively, only 12 of the 45 patients
      (26.7%) needed antihypertensive drug(s). CONCLUSIONS: Laparoscopic adrenalectomy
      is a safe and effective way to treat primary hyperaldosteronism. Many of the
      patients in whom hypertension persisted postoperatively were men or elderly.

PMID- 16646655
TI  - Comparison of results of virtual-reality simulator and training model for basic
      ureteroscopy training.
AB  - BACKGROUND AND PURPOSE: The traditional method of acquiring surgical skills is by
      apprenticeship and involves an extensive period of training with patients. Model
      based and virtual reality simulation is gaining interest as alternative training,
      allowing repetitive practice in a low-risk environment. The objective of this
      study was to determine if a materials, model-based training format and an
      interactive virtual-reality simulator could provide equivalent teaching of basic
      ureteroscopy skills to the inexperienced medical student. SUBJECTS AND METHODS:
      Sixteen first-year medical students received the same didactic session and video
      viewing on cystoscopy, guidewire access to the upper urinary tract, and
      ureteroscopy with intracorporeal laser lithotripsy and stone extraction by the
      same instructor. The participants were then randomized into two study groups:
      Group 1 was trained on the ureteroscopy training model (TMU) from Limbs & Things
      and Group 2 on the Simbionix UROMentor virtual-reality simulator (VRS) until the
      participants could perform the procedure independently. Two months later, the
      participants independently performed a ureteroscopic procedure on a pig
      kidney/ureter model and were graded from 1 to 5 on their ability to complete the
      steps of the procedure and the quality of their performance (handling of tissue,
      efficiency, instrument handling, knowledge of instruments, flow of operation, use
      of assistants, and knowledge of the specific procedure) for a possible total of
      35 points. RESULTS: All participants were able to perform the steps of the
      procedure correctly. The TMU group and the VRS group received a mean of 22.9 +/-
      4.8 and 23.6 +/- 5.4 points, respectively (P = 0.38) for their qualitative
      assessment. CONCLUSION: The medical students' skills and ability to perform a
      basic ureteroscopic stone-management procedure was independent of the training
      modality (VRS or TMU). Incorporating either of these devices into the preliminary
      training of urology residents may improve their initial clinical performance of
      these skills.

PMID- 16646656
TI  - Comparison of nitinol urethral stent infections with indwelling catheter
      associated urinary-tract infections.
AB  - BACKGROUND AND PURPOSE: To determine the efficacy of intraurethral metal stents
      in preventing or eradicating urinary-tract infections (UTI) during the management
      of bladder outlet obstruction (BOO) by comparing the frequency and nature of the
      infections with indwelling-catheter-associated UTI. PATIENTS AND METHODS: The SAS
      relative-risk test was used to compare the risks of UTI in 76 patients with
      temporary urethral stents, 60 patients with BOO who had never been catheterized
      nor stented, and 34 patients with a permanent indwelling urethral catheter
      (PIUC). Infection was assessed 1 month after placement of the devices. Scanning
      electron microscopy (SEM) of the proximal and distal pieces of the stents removed
      from five patients with and five patients without UTI was carried out in a search
      for predisposing changes on the surfaces. RESULTS: After insertion of the
      catheter, UTI developed in 79.4% of the patients who originally had sterile
      urine. However, after insertion of the stent, UTI developed in only 40.9% of the
      patients with sterile urine. In 21 (44.6%) of the catheterized patients who had
      infected urine, UTI was eradicated after stent insertion. The SEM analysis of the
      stents showed that a thick organic layer had formed only on the infected devices
      but with no sign of erosion. CONCLUSION: Urinary infection is a significant
      problem in patients with PIUC but is significantly less frequent and less severe
      in patients with urethral stents. This advantage of stents over the conventional
      urethral catheter, in addition to their obvious convenience for the patient, make
      them good alternatives to reduce the risk of UTI.

PMID- 16646657
TI  - Effect of multisite radiofrequency ablation on porcine renal function.
AB  - BACKGROUND AND PURPOSE: The acute and long-term effects of radiofrequency
      ablation (RFA) on kidney function have not been well studied. The functional
      change when RFA is used in combination with renal ischemia is likewise unknown.
      Our goal was to determine the change in renal function caused by various volumes
      of RFA on a porcine kidney model and the effect cold ischemia had on the results.
      MATERIALS AND METHODS: Twenty-two female pigs with solitary kidneys underwent
      various volumes of RFA both with and without cold ischemia. Animals were divided
      into control, 10%, 15%, and 20% ablation of the total kidney volume. Measurements
      of creatinine were obtained for 2 weeks. RESULTS: In the nonischemic group, the
      mean acute (day 1-3) creatinine changes in control, 10%, 15%, and 20% ablations
      were 0.6, 2.4, 1.7, and 2.6 mg/dL, respectively. In the cold-ischemia group, the
      mean acute creatinine changes were 0.85, 2.33, 3.3, and 3.75 mg/dL, respectively.
      Regression line analysis demonstrated a positive linear relationship in both
      groups. Fourteen-day mean creatinine changes for the nonischemic group were
      similar to those in the control animals and did not show a correlation with
      ablation volume. The mean creatinine changes at 14 days in the cold-ischemia
      group showed a positive linear correlation with ablation volume. CONCLUSIONS: The
      volume of RFA correlates with an acute change in renal function in the porcine
      model for both nonischemic and cold-ischemia groups. This study may help predict
      the extent of acute renal dysfunction in patients undergoing RFA for large or
      multiple renal masses. These results also suggest renal function may recover
      after nonischemic RFA.

PMID- 16646658
TI  - Evaluation of laparoscopic performance with alteration in angle of vision.
AB  - BACKGROUND AND PURPOSE: Optimal placement allows intuitive laparoscope
      positioning between two working trocars (0 degrees angle). However, this
      configuration may require the assistant to operate in an awkward position. We
      evaluated the effect of alteration of laparoscope position on surgeon performance
      and correlated this with surgical experience. SUBJECTS AND METHODS: Participants
      were stratified by laparoscopic experience. Group 1 (N = 10) was naive (no
      surgical experience), group 2 (N = 7) had moderate laparoscopic experience (1-100
      cases), and group 3 (N = 6) was laparoscopically experienced (>100 cases).
      Participants were timed performing a simple laparoscopic task three times in a
      trainer with camera angles randomized along the horizontal plane: 0 degrees , 45
      degrees , 90 degrees , 135 degrees , and 180 degrees . RESULTS: All participants
      showed progressive deterioration in performance as the angle deviated from
      baseline. The mean time required to complete the tasks was significantly higher
      for group 1 v groups 2 and 3 at 135 degrees (158 v 77 and 73 seconds) and 180
      degrees (153 v 89 and 86 seconds). Performance curves for each group revealed
      more pronounced deterioration of performance with alteration in the angle of
      vision in group 1 than in groups 2 and 3 (P < 0.01). There was no difference
      between groups 2 and 3 (P = 0.19). CONCLUSIONS: Even modest alteration in
      laparoscopic perspective results in deterioration of performance for all levels
      of surgical experience. Experienced laparoscopists adapt more quickly to
      complexities presented by alteration in camera angles. Novice surgeons should
      focus on trocar positioning to maintain intuitive surgical perspective and should
      refrain from working with alterations in camera angles until significant
      laparoscopic experience has been gained.

PMID- 16646661
TI  - Neural specification of stem cell differentiation.

PMID- 16646662
TI  - Human mesenchymal stem cells express neural genes, suggesting a neural
      predisposition.
AB  - Because of their unique attributes of plasticity and accessibility, bone marrow
      derived mesenchymal stem cells (MSCs) may find use for therapy of
      neurodegenerative disorders. Our previous studies of adult human MSCs
      demonstrated that these cells express an extensive assortment of neural genes at
      a low but clearly detectable level. Here, we report expression of 12 neural
      genes, 8 genes related to the neuro-dopaminergic system, and 11 transcription
      factors with neural significance by human MSCs. Our results suggest that, as
      opposed to cells that do not express neural genes, human MSCs are predisposed to
      differentiate to neuronal and glial lineages, given the proper conditions. Our
      findings add a new dimension in which to view adult stem cell plasticity, and may
      explain the relative ease with which MSCs, transplanted into the central nervous
      system (CNS) differentiate to a variety of functional neural cell types. Our
      results further promote the possibility that adult human MSCs are promising
      candidates for cell-based therapy of neurodegenerative diseases.

PMID- 16646663
TI  - Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell
      death and neurogenesis of neural progenitor cells.
AB  - Acetylation of histones and nonhistone proteins is an important post
      translational modification involved in the regulation of gene expression in
      mammalian cells. Dysfunction of histone acetyltransferase (HAT) is often
      associated with the manifestation of several diseases. In this report, HATs are
      new targets for the development of therapeutics. Our studies first proved that
      curcumin induces histone hypoacetylation in brain cancer cells and finally
      induces apoptotic cell death through a (PARP)- and caspase 3-mediated manner. In
      addition, curcumin induces recontrolling of neural stem cell fates. It induces
      effective neurogenesis, synaptogenesis, and migration of neural progenitor cells
      in vitro in brain-derived adult neural stem cells. We also confirmed the
      neurogenic effect of curcumin in our in vivo experiments. Curcumin actively
      suppressed differentiation in astrocytes while promoting differentiation into the
      neurons associated with decrease of histone H3 and H4 acetylation. We suggest
      that histone hypoacetylation plays an important role in determine stem cell fate
      through controlling the simultaneous expression of many genes. Thus, the present
      finding that curcumin, a nontoxic dietary compound, is a histone
      acetyltransferase inhibitor would supply a new window to understand further the
      molecular mechanism of histone acetylase inhibitors (HAI) in cancer and neural
      stem cells and provide a new target molecule for treating central nervous system
      disorders.

PMID- 16646664
TI  - Transcription Factor IIA tau is associated with undifferentiated cells and its
      gene expression is repressed in primary neurons at the chromatin level in vivo.
AB  - The levels of General Transcription Factor (TF) IIA were examined during
      mammalian brain development and in rat embryo fibroblasts and transformed cell
      lines. The large TFIIA subunit paralogues alphabeta and tau are largely produced
      in unsynchronized cell lines, yet only TFIIA alphabeta is observed in a number of
      differentiated tissue extracts. Steady-state protein levels of the TFIIA tau,
      alphabeta, and gamma subunits were significantly reduced when human embryonal
      (ec) and hepatic carcinoma cell lines were stimulated to differentiate with
      either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec
      cells required replating to induce a neuronal phenotype and loss of detectable
      TFIIA tau and gamma proteins. High levels of TFIIA tau, alphabeta, and gamma and
      Sp factors were identified in extracts from human fetal and rat embryonic day-18
      brains, but not in human and rat adult brain extracts. A high histone H3
      Lys9/Lys4 methylation ratio was observed in the TFIIA tau promoter of primary
      hippocampal neurons from day-18 rat embryos, suggesting that repressive
      epigenetic marks of chromatin prevent TFIIA tau from being transcribed in
      neurons. We conclude that TFIIA tau is associated with undifferentiated cells
      during development, yet is down-regulated at the chromatin level upon cellular
      differentiation.

PMID- 16646665
TI  - Isolation of adult rhesus neural stem and progenitor cells and differentiation
      into immature oligodendrocytes.
AB  - Neural stem and progenitor cells (NSPCs) have been isolated from several regions
      of the brain from mice, rats, and humans. These cells possess the characteristics
      of self-renewal and differentiation along all major neural lineages. Herein, the
      first isolation of NSPCs from the adult rhesus macaque brain and characterization
      of these cells based on their gene and protein expression profile, self-renewal,
      and ability to differentiate along an oligodendrocyte lineage are described. Flow
      cytometric analysis revealed that this cell population is CD90(+)/CD164(+)/CD34(
      ) and, therefore, resembles a nonhematopoietic stem cell population. Similar to
      other mesenchymal and neural stem cell populations, rhesus NSPCs cells express
      stemness-related genes, including the transcription factors Oct-4, Rex-1, and Sox
      2 and the gene encoding for the intermediate filament protein nestin. The co
      expression of the neural and glial markers MAP2ab, GFAP, NF-L, and NeuroD was
      also observed at both the mRNA and protein levels. When rhesus NSPCs were induced
      to differentiate with a cocktail of retinoic acid and the neurotrophins (NGF,
      BDNF, and NT-3), they underwent morphologic changes including taking on an
      oligodendrocyte precursor morphology. Along with these phenotypic changes, a
      decrease in MAP2ab expression and new expression of the oligodendrocyte precursor
      protein O4 were observed. Taken together, these results demonstrate the existence
      of a stem and progenitor cell-like population in the nonhuman primate brain,
      which may have the potential to generate oligodendroglia for use in the
      development of cellular therapies for demyelinating diseases.

PMID- 16646666
TI  - Uniform adherent neural progenitor populations from rhesus embryonic stem cells.
AB  - Rhesus and human embryonic stem cells (ESCs) are similar, making rhesus ESCs an
      appropriate preclinical allograft model for refining stem cell therapies. Use of
      rhesus ESC-derived neural progenitors (NPs) in preclinical applications will be
      enhanced if the neural derivation process is scalable and free from contaminating
      ESCs or nonneural cells. In this study, we have quantified temporal gene
      expression changes of rhesus ESC differentiated to uniform NPs using simple
      feeder-free adherent cultures. NPs exhibited a significant up-regulation of
      neural-specific genes and a downregulation of pluripotency genes. Additionally,
      expression of Hu, MAP2, and Tuj1, shows that NPs can form post-mitotic neurons.
      This study represents a simple and scalable means of producing adherent primate
      NPs for preclinical testing of neural cell-based therapy.

PMID- 16646667
TI  - Comparison of growth and differentiation of fetal and adult rhesus monkey
      mesenchymal stem cells.
AB  - The goal of this study was to compare the growth and differentiation potential of
      fetal and adult rhesus monkey (Macaca mulatta) mesenchymal stem cells (rhMSCs).
      rhMSCs were obtained from healthy early third-trimester fetal (n = 3) and adult
      (n = 3) rhesus monkey bone marrow. Fetal rhMSCs were plated at 10, 50, 100, or
      1,000 cells/cm(2) in medium containing 10% or 20% infant monkey serum (IMS) or
      fetal bovine serum (FBS). Fetal rhMSCs grown at 1,000 cells/cm(2) in 20% FBS
      showed faster growth rates and differentiation toward adipogenic, chondrogenic,
      and osteogenic lineages when compared to other culture conditions and to adult
      cells (p < 0.05). Fetal rhMSC showed higher population doubling times (11.3 +/-
      0.5) when compared to adult cells (7.3 +/- 0.8) during the first three passages.
      Adult rhMSC did not grow beyond the third passage under all culture conditions,
      including those supplemented with insulin-like growth factor (IGF)-I, IGF-II,
      platelet-derived growth factor (PDGF), and fibroblast growth factor-2 (FGF-2).
      After the third passage, adult rhMSC cultures were observed with large syncytia
      and with evidence of apoptosis. Cells obtained from these cultures tested
      positive for simian foamy virus (SFV) by PCR, RT-PCR, and immunofluorescent
      assay. Adult rhMSCs cultured with 10 microM tenofovir, an antiviral agent, showed
      normal growth and differentiation for over 20 population doublings. These
      findings suggest that: (1) fetal rhMSCs possess greater self-renewal and
      differentiation potential when compared to adult cells; and (2) SFV can inhibit
      proliferation of adult rhMSCs in culture, whereas the addition of tenofovir can
      successfully suppress SFV replication in vitro and result in resumed growth.

PMID- 16646668
TI  - Following the differentiation of human pluripotent stem cells by proteomic
      identification of biomarkers.
AB  - Following the differentiation of cultured stem cells is often reliant on the
      expression of genes and proteins that provide information on the developmental
      status of the cell or culture system. There are few molecules, however, that show
      definitive expression exclusively in a specific cell type. Moreover, the reliance
      on a small number of molecules that are not entirely accurate biomarkers of
      particular tissues can lead to misinterpretation in the characterization of the
      direction of cell differentiation. Here we describe the use of technology that
      examines the mass spectrum of proteins expressed in cultured cells as a means to
      identify the developmental status of stem cells and their derivatives in vitro.
      This approach is rapid and reproducible and it examines the expression of several
      different biomarkers simultaneously, providing a profile of protein expression
      that more accurately corresponds to a particular type of cell differentiation.

PMID- 16646669
TI  - Massively parallel signature sequencing profiling of fetal human neural precursor
      cells.
AB  - We have examined gene expression in multipotent neural precursor cells (NPCs)
      derived from human fetal (f) brain tissue and compared its expression profiles
      with embryonic stem (ESC) cells, embryoid body cell (EBC), and astrocyte
      precursors using the technique of massively parallel signature sequencing (MPSS).
      Gene expression profiles show that fNPCs express core neural stem cells markers
      and share expression profiles with astrocyte precursor cells (APCs) rather than
      ESC or EBC. Gene expression analysis shows that fNPCs differ from other adult
      stem and progenitor cells in their marker expression and activation of specific
      functional networks such as the transforming growth factorbeta (TGFbeta) and
      Notch signaling pathways. In addition, our results allow us to identify novel
      genes expressed in fNPCs and provide a detailed profile of fNPCs.

PMID- 16646670
TI  - Fetal cartilage engineering from amniotic mesenchymal progenitor cells.
AB  - We determined whether cartilage could be engineered from mesenchymal progenitor
      cells (MPCs) normally found in amniotic fluid. Mesenchymal amniocytes were
      isolated from ovine amniotic fluid samples (n = 5) and had their identity
      confirmed by immunocytochemistry. Cells were expanded and then cultured as
      micromass pellets (n = 5) in a chondrogenic medium containing transforming growth
      factor-beta2 (TGF-beta2) and insulin growth factor-1 (IGF-1) for 6-12 weeks.
      Pellets derived from fetal dermal fibroblasts (n = 4) were cultured under
      identical conditions. Additionally, expanded mesenchymal amniocytes were seeded
      onto biodegradable polyglycolic acid scaffolds (n = 5) and maintained in the same
      chondrogenic medium within a rotating bioreactor for 10-15 weeks. Engineered
      specimens were analyzed quantitatively and compared with native fetal hyaline
      cartilage samples (n = 5). Statistical analysis was by the unpaired Student's t
      test (p < 0.05). The isolated cells stained positively for vimentin and
      cytokeratins-8 and -18, but negatively for CD31. Micromass pellets derived from
      mesenchymal amniocytes exhibited chondrogenic differentiation by both standard
      and matrix-specific staining. In contrast, these findings could not be replicated
      in dermal fibroblast-based pellets. The engineered constructs derived from
      mesenchymal amniocytes similarly displayed histological evidence of chondrogenic
      differentiation and maintained their original size and three-dimensional
      architecture. Quantitative assays of the engineered constructs revealed lower
      concentrations of collagen type II, but similar amounts of glycosaminoglycans,
      elastin, and DNA, when compared to native fetal hyaline cartilage. We conclude
      that mesenchymal amniocytes can be used for the engineering of cartilaginous
      tissue in vitro. Cartilage engineering from the amniotic fluid may become a
      practical approach for the surgical treatment of select congenital anomalies.

PMID- 16646671
TI  - Growth of teratomas derived from human pluripotent stem cells is influenced by
      the graft site.
AB  - Pluripotent stem cells transplanted into immune-deficient mice form complex
      teratomas. Although such tumors are generally haphazard in their organization,
      they do contain some structures that resemble tissues normally seen in the
      embryo. As a consequence, the teratoma model is useful for exploring the
      developmental potential of stem cells and studying certain aspects of tissue
      development. To further our understanding of this process, we examined whether
      the anatomical location into which human pluripotent stem cells were grafted
      influenced their growth in situ. Here we report that cells grafted into the liver
      rapidly produced large tumors containing predominantly immature cells. In
      contrast, subcutaneous implants were significantly slower growing and eventually
      formed tumors composed of differentiated tissues. The alternative growth patterns
      recorded between these two graft sites indicates how environmental cues affect
      stem cell behavior. This approach may lead to the identification of new ways to
      control stem cell growth and differentiation.

PMID- 16646672
TI  - Overexpression of stromal cell-derived factor-1 enhances endothelium-supported
      transmigration, maintenance, and proliferation of hematopoietic progenitor cells.
AB  - To clarify the direct effects of aberrant overexpression of stromal cell-derived
      factor-1 (SDF-1) by the human endothelium on circulating progenitor cells, we
      overexpressed the SDF-1 gene in human umbilical vein endothelial cells using an
      adenoviral vector (HUVEC/AdeSDF-1) and examined the endothelium-supported
      trafficking and growth of hematopoietic progenitor cells (HPCs) in mobilized
      peripheral blood (mPB). In culture, the HUVEC/AdeSDF-1 monolayers induced the
      migration of mPB CD34(+) cells underneath the endothelium within a few hours,
      whereas HUVEC monolayers that expressed the LacZ gene (HUVEC/AdeLacZ) did not
      have this effect. In the Transwell system, the HUVEC/AdeSDF-1 cells supported a
      higher level of spontaneous transmigration of mPB CD34(+) cells than did the
      HUVEC/AdeLacZ cells. The co-culturing of mPB CD34(+) cells with HUVEC/ AdeSDF-1
      cells led to a greater expansion of CD45(+) cells and colony-forming cells and
      reduced cellular apoptosis. Furthermore, the co-culturing of mPB CD34(+) cells
      with HUVEC/AdeSDF-1 cells led to the formation of numerous cobblestone-like
      areas, whereas co-cultures of mPB CD34(+) cells and HUVEC/AdeLacZ supported only
      a few cobblestone-like areas. These results indicate that SDF- 1 produced by
      endothelial cells plays an important role not only in the transmigration but also
      in the growth of HPCs that are in contact with endothelial cells. Our findings
      suggest that the enhanced expression and production of SDF-1 in the endothelium
      are essential steps for stem cell or progenitor cell recruitment to specific
      tissues and for the maintenance of these cells in situ.

PMID- 16646673
TI  - No polarization of type 1 or type 2 precursor dendritic cells in peripheral blood
      stem cell collections of non-hodgkin's lymphoma patients mobilized with
      cyclophosphamide plus G-CSF, GM-CSF, or GM-CSF followed by G-CSF.
AB  - Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a
      role in immune reconstitution after autologous transplantation. Recent reports
      suggest that mobilization with granulocyte colony-stimulating factor (G-CSF)
      containing regimens polarizes DCs into pDC2, which could potentially result with
      increased Th2 response and decreased graft-versus-host disease (GVHD) in
      allogeneic transplantation and with decreased cytotoxic Th1 response and graft
      versus tumor effect, which in autologous transplantation could translate into
      increased relapse rate. Previously, we have shown that non-Hodgkin's lymphoma
      (NHL) patients receiving cyclophosphamide (CTX) plus granulocyte- macrophage (GM)
      CSF, G-CSF or GM-CSF followed by G-CSF for stem cell collection, mobilize up to
      five-fold more mature CD80(+) DCs compared to CTX plus G-CSF mobilized patients.
      Here, we analyzed samples from the same study for the number of pDC1 and pDC2
      subsets in blood and apheresis products obtained from these patients. Samples
      from 29 patients were collected. Patients mobilized with CTX plus G-CSF collected
      a mean of 1.2 +/- 0.4 x 10(6) pDC1/kg per day and 2.2 +/- 1 x 10(6) pDC2/kg per
      day, whereas patients mobilized with CTX plus GM-CSF collected a mean of 1.1 +/-
      0.5 x 10(6) pDC1 and 1.5 +/- 0.9 x 10(6) pDC2/kg per day. Patients mobilized with
      CTX plus GM-CSF followed by G-CSF collected 2.5 +/- 1.1 x 10(6) pDC1 and 2 +/-
      0.5 x 106 pDC2/kg per day, with significantly higher levels of pDC1 +/- pDC2
      cells. No significant difference was observed in pDC1/pDC2 ratio between the
      three mobilization arms. Patients mobilized with the GM-CSFcontaining regimen had
      a higher probability for survival compared to patients receiving G-CSF alone
      (median of 55 months vs. 15 months; p = 0.02). These results support the
      hypothesis that higher levels of DCs in the graft might be associated with
      prolonged survival of autotransplanted NHL patients. Further similar studies are
      merited in a larger population of NHL patients.

PMID- 16646674
TI  - Nucleofection, an efficient nonviral method to transfer genes into human
      hematopoietic stem and progenitor cells.
AB  - The targeted manipulation of the genetic program of single cells as well as of
      complete organisms has strongly enhanced our understanding of cellular and
      developmental processes and should also help to increase our knowledge of primary
      human stem cells, e.g., hematopoietic stem cells (HSCs), within the next few
      years. An essential requirement for such genetic approaches is the existence of a
      reliable and efficient method to introduce genetic elements into living cells.
      Retro- and lentiviral techniques are efficient in transducing primary human HSCs,
      but remain labor and time consuming and require special safety conditions, which
      do not exist in many laboratories. In our study, we have optimized the
      nucleofection technology, a modified electroporation strategy, to introduce
      plasmid DNA into freshly isolated human HSC-enriched CD34(+) cells. Using
      enhanced green fluorescent protein (eGFP)-encoding plasmids, we obtained
      transfection efficiencies of approximately 80% and a mean survival rate of 50%.
      Performing functional assays using GFU-GEMM and long-term culture initiating
      cells (LTC-IC), we demonstrate that apart from a reduction in the survival rate
      the nucleofection method itself does not recognizably change the short- or long
      term cell fate of primitive hematopoietic cells. Therefore, we conclude, the
      nucleofection method is a reliable and efficient method to manipulate primitive
      hematopoietic cells genetically.

PMID- 16646675
TI  - Neural crest as the source of adult stem cells.
AB  - Recent studies suggest that adult stem cells can cross germ layer boundaries. For
      example, bone marrow-derived stem cells appear to differentiate into neurons and
      glial cells, as well as other types of cells. How can stem cells from bone
      marrow, pancreas, skin, or fat become neurons and glia; in other words, what
      molecular and cellular events direct mesodermal cells to a neural fate?
      Transdifferentiation, dediffereniation, and fusion of donor adult stem cells with
      fully differentiated host cells have been proposed to explain the plasticity of
      adult stem cells. Here we review the origin of select adult stem cell populations
      and propose a unifying hypothesis to explain adult stem cell plasticity. In
      addition, we outline specific experiments to test our hypothesis. We propose that
      peripheral, tissue-derived, or adult stem cells are all progeny of the neural
      crest.

PMID- 16646676
TI  - How editorial turmoil can sink a journal, but not thyroid.

PMID- 16646677
TI  - Mitochondrial activities of a cell line derived from thyroid Hurthle cell tumors.
AB  - OBJECTIVE: We conducted a study on the functional characteristics of mitochondria
      in an oxyphilic thyroid tumor cell line, which may provide useful clues about
      Hurthle cell tumors carcinogenesis. DESIGN: The functional study on thyroid
      tumors with cell oxyphilia (Hurthle cell tumors), characterized by mitochondrial
      hyperplasia, was carried out in XTC.UC1, and B-CPAP, an oxyphilic and
      nonoxyphilic thyroid tumor cell line, respectively. MAIN OUTCOME: XTC.UC1 cell
      line showed higher activity of mitochondrial respiratory complexes I and II and
      decreased activity of complex III. The increased activity of complex I was not
      matched by increased expression of complex I subunits. The XTC.UC1 cells relied
      mostly on oxidative phosphorylation for energy conservation, although their
      mitochondrial energetic function was less efficient when related to mitochondrial
      content of the cells. Finally, the oxyphilic cell line produced significantly
      higher amounts of reactive oxygen species (ROS) in comparison with B-CPAP cell
      line. CONCLUSION: The involvement of ROS in mitochondrial biogenesis and
      proliferation as well as in carcinogenesis and apoptosis indicate that
      differences in activity of respiratory chain components and their unbalance may
      be responsible for development of morphological and functional changes observed
      in thyroid tumors with cell oxyphilia.

PMID- 16646678
TI  - Activation of protein kinase C delta induces growth arrest in NPA thyroid cancer
      cells through extracellular signal-regulated kinase mitogen-activated protein
      kinase.
AB  - Protein kinase C (PKC) is a family of serine-threonine kinases that regulate many
      cell processes. To study the role of PKCdelta in thyroid cancer cells, we used a
      replication-deficient adenovirus (PKCdeltaAdV), to tightly control PKCdelta
      expression. In NPA cells, activation of wild-type (WT) PKCdelta with phorbol 12
      myristate 13-acetate (PMA) induced an arrest in cell growth at G(1) phase, which
      was itself inhibited by the PKCdelta inhibitor rottlerin. Furthermore,
      overexpression of a dominant negative PKCdelta did not induce G(1) arrest. These
      findings strongly suggested that PKCdelta induced cell growth arrest in NPA
      cells. We investigated the mechanism of G1 arrest by examining G(1)-related
      proteins and mitogen-activated protein kinase (MAPK) by Western blotting. After
      activation of WTPKCdelta with PMA, cyclin E expression and retinoblastoma protein
      (Rb) phosphorylation decreased; the expression of p27(Kip1) increased and the
      phosphorylation of extracellular signal-regulated kinase (ERK) MAPK decreased.
      These results indicated that the activation of PKCdelta induced cell growth
      arrest in NPA cells, through an ERK MAPK-p27(Kip1)-cyclin E-pRb pathway. PKCdelta
      may therefore be an effective molecular target for novel therapy in thyroid
      cancer.

PMID- 16646679
TI  - Antibodies focused on the human autoantibody immunodominant region are induced by
      B lymphocytes that constitutively express thyroid peroxidase diverted to the
      major histocompatibility complex II pathway.
AB  - We addressed the question of why naturally occurring, polyclonal thyroid
      peroxidase (TPO) autoantibodies have a restricted epitopic repertoire to an
      immunodominant region (IDR). We hypothesized that immunizing BALB/c mice with
      major histocompatibililty complex (MHC) class II compatible B lymphocytes (A20
      cells) preferentially diverting TPO to the MHC class II pathway would produce TPO
      antibodies with an epitopic specificity similar to human autoantibodies, namely
      to the IDR. For this purpose we stably expressed in A20 cells a fusion protein of
      TPO sandwiched between the signal peptide and transmembrane/cytoplasmic tail of
      the lysosome- associated membrane protein (LAMP) 1. Expression of LAMP1-TPO in
      A20 B cells was confirmed by flow cytometry using a TPO monoclonal antibody. Mice
      injected intraperitoneally with LAMP1-TPO A20 B cells developed TPO antibodies
      detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry and (125)I
      TPO precipitation. However, TPO antibody levels were low. Most important,
      competition for TPO antibody binding by recombinant human TPO autoantibody Fab
      indicated that more than 80% of the polyclonal TPO antibodies in the immunized
      mice were to the human autoantibody IDR. In summary, injecting mice with B
      lymphocytes that constitutively express TPO diverted to the MHC class II pathway
      generates antibodies with epitopes similar to those of human TPO autoantibodies,
      namely to the autoantibody IDR. However, these antibodies are of low titer that
      is itself associated with this epitopic bias.

PMID- 16646680
TI  - Possible interaction between HLA-DRbeta1 and thyroglobulin variants in Graves'
      disease.
AB  - Graves' disease (GD) is influenced by two major susceptibility loci, HLA-DR3 and
      thyroglobulin (Tg). Recently we have shown that specific HLA-DR and Tg gene
      sequences predispose to Graves' disease. Individuals carrying at least one
      arginine at position 74 of the DRbeta1 chain (denoted the R- genotype) have a
      significantly increased risk of GD, as do individuals homozygous for the single
      nucleotide protein (SNP) in exon 33 of the Tg gene (denoted the CC genotype).
      Therefore, for the current study we hypothesized that these two genes may
      interact to influence the etiology of GD. To test this hypothesis, we analyzed
      the genotypes of 185 Caucasian patients with GD and 143 Caucasian controls for
      both genes. We tested for an interaction effect, that is, is one gene's effect on
      GD greater when the other gene is also present than when the other gene is
      absent? A logistic regression analysis yielded an estimate of 4.31 for the
      interaction term (p = 0.053). Our results may suggest an interaction between the
      R- and CC variants in conferring susceptibility to GD. These results, if
      confirmed, may imply that these two variants interact biologically to increase
      the odds of GD.

PMID- 16646681
TI  - Triiodothyronine acutely increases blood flow in the ventricles and kidneys of
      anesthesized rabbits.
AB  - Thyroid hormone (triiodothyronine [T(3)]) has various nongenomic effects,
      including alterations in glucose and fatty acid metabolism, augmentation of
      intracellular Ca(2+), enhancement of myocardial contractility, and vascular
      dilatation. However, its effect on regional blood flow remains to be established.
      We have measured the effect of T(3) on blood flow in major organs of anesthetized
      rabbits in vivo using the microsphere method. Under artificial respiration,
      nonradioactive microspheres (5 x 10(5)) labeled with barium were injected to
      measure blood flow at control level. Then, T(3) (50 microg/kg per milliliter) was
      administered and microspheres labeled with iodine (5 x 10(5)) were injected. The
      atria, ventricles, kidneys, and right upper limb were excised and their contents
      of microspheres were evaluated. Blood flow in the ventricles was significantly
      increased by T(3) (2.9 +/- 0.3 versus 3.4 +/- 0.3 mL/min per gram, vehicle versus
      T(3)). Similarly, blood flow in the kidneys was significantly higher after T(3)
      injection (4.3 +/- 0.5 versus 5.1 +/- 0.5 mL/min per, vehicle versus T(3)). The
      blood flow in the atria and skeletal muscles remained unchanged. These results
      indicate that the vasodilatory response to T(3) is not uniform and occurs
      preferentially in major organs such as cardiac ventricles and kidneys; this may
      be relevant to the T(3)-induced improvement of cardiac function.

PMID- 16646682
TI  - Radiofrequency ablation of benign cold thyroid nodules: initial clinical
      experience.
AB  - CONTEXT AND OBJECTIVE: To evaluate the efficacy and safety of ultrasound (US)
      guided percutaneous radiofrequency (RF) ablation for benign cold thyroid nodules
      as a nonsurgical therapeutic modality. DESIGN, INTERVENTION, AND PATIENTS: A
      total of 35 benign cold thyroid nodules in 30 euthyroid patients (M:F = 2:28;
      mean age 39.1 years) underwent percutaneous RF ablation with a 1-cm-internally
      cooled electrode. Seventy-seven percent (23/30) of patients required conscious
      sedation for discomfort. We evaluated the tumor size, cystic component,
      vascularity (by color Doppler US), and the severity of mass-related symptoms
      before treatment. We assessed the therapeutic efficacy and safety of RF ablation
      by clinical and US follow-up (median 6.4 months). MAIN OUTCOME AND RESULTS: The
      volume of the tumors before ablation had a range of 0.6-28.2 mL (mean, 6.3 mL).
      The residual volume was 53.5% +/- 26.5% of original at 1.1-2.9 months (n = 32),
      36.2% +/- 27.4% at 3.0-5.9 months (n = 20), 30.7% +/- 25.0% at 6.0-8.9 months (n
      = 15), and 11.8% +/- 10.9% at 9.0-18.5 months (n = 13). Mixed/mainly cystic
      tumors showed a significantly better response than mainly solid tumors (p <
      0.05). Difference in vascularity did not affect the treatment response. Thyroid
      function after the procedure was maintained as normal in all patients. Eighty
      eight percent of the patients reported an improvement of their symptoms. There
      was no major complication other than vocal cord palsy in one patient (3.3%).
      CONCLUSION: RF ablation may be an effective and safe nonsurgical technique to
      treat benign cold thyroid nodules.

PMID- 16646683
TI  - Impact of short-term hypothyroidism on systemic anticoagulation in patients with
      thyroid cancer and coumarin therapy.
AB  - Unlike hyperthyroidism, few data exist regarding the impact of hypothyroidism on
      systemic anticoagulation with coumarin derivates. Therefore, we evaluated a
      potential impact of short-term hypothyroid conditions on systemic anticoagulation
      with coumarin derivates in patients after complete thyroidectomy for treatment of
      thyroid cancer. Fifteen patients with differentiated thyroid cancers and
      continued international normalized ratio (INR)-adjusted therapy with coumarin
      derivates were included in this retrospective analysis. A total of 88 laboratory
      tests was analyzed. INR values were compared between thyroid-stimulating hormone
      (TSH) values greater than 10 and 10 mU/L or less. An INR value of less than 2.0
      was defined as being out of the therapeutic range. Analysis of significant
      differences between categorized TSH and INR values were performed by using X(2)
      analysis, correlation of continuous TSH and INR values by using the Pearson's
      analysis. When TSH was greater than 10 mU/L (n = 50) the INR value was less than
      2.0 in 76.0% (n = 38) cases. In contrast, the INR value was less than 2.0 in only
      21.1% (n = 8; p < 0.0001) of patients with TSH of 10 mU/L or less (n = 38).
      Correlation between continuous TSH and INR values was r = -0.589 (p < 0.0001).
      Based on the results of the present study, it seems to be necessary to monitor
      the anticoagulation parameters more often in patients with hypothyroidism and
      either to correct the hypothyroid state, or in cases of desired hypothyroid
      conditions, to adjust the therapy with coumarin derivates in order to ensure a
      sufficient anticoagulation.

PMID- 16646684
TI  - The impact of overt and subclinical hyperthyroidism on skeletal muscle.
AB  - OBJECTIVE: Patients with overt hyperthyroidism (OH) commonly have proximal limb
      muscle weakness that improves after correction of hyperthyroidism. It is unclear,
      however, if patients with milder degrees of hyperthyroidism (referred to as
      subclinical hyperthyroidism or SCH) may also have a degree of muscle weakness.
      This may have clinical relevance as SCH patients are often elderly and may
      therefore have concurrent sarcopenia of aging and would represent a previously
      unrecognized complication of SCH. DESIGN: We measured both thigh strength and
      cross-sectional area in patients with OH (n = 30) or SCH (n = 24), both prior to
      treatment of hyperthyroidism and again at 6-9 months after the restoration of a
      euthyroid state. Euthyroid controls (n = 48) were studied at similar time
      intervals. MAIN OUTCOME: Prior to treatment, both knee flexor and extensor muscle
      strength was reduced in both patients with OH and SCH compared to controls (p <
      0.05). After treatment all strength measurements improved in the OH group (p <
      0.01) while in the SCH group the majority of muscle strength measurements
      improved (p < 0.05). Midthigh muscle cross-sectional area was reduced in both the
      OH and SCH group at baseline (p < 0.05) compared to controls and increased
      significantly following treatment (p < 0.05). There were no significant changes
      in any parameter in the euthyroid control (EC) group during the study period.
      CONCLUSIONS: The finding that muscle strength and cross-sectional area are
      reduced in SCH and improved after treatment lends support for the clinical
      decision to treat rather than observe this condition. This may have particular
      relevance to certain SCH patient groups including the elderly who are prone to
      falls and athletically active younger patients who require optimal skeletal
      muscle function.

PMID- 16646685
TI  - Long-term thyrotropin-suppressive therapy with levothyroxine impairs small and
      large artery elasticity and increases left ventricular mass in patients with
      thyroid carcinoma.
AB  - BACKGROUND: Exogenous subclinical hyperthyroidism, caused by long-term
      thyrotropin (TSH)-suppressive treatment with levothyroxine (LT(4)), is associated
      with several cardiovascular abnormalities. In order to assess the effect of long
      term thyroid hormone-suppressive therapy on the blood vessels and myocardium, we
      determined the arterial elasticity, using the pulse wave contour analysis.
      METHODS AND RESULTS: Twenty-six athyreotic patients receiving TSH-suppressive
      LT(4) therapy for periods ranging from 3 to 21 years at a mean daily dose of 2.25
      +/- 0.5 microg/kg per day were included in the study. Twenty six age- and gender
      matched healthy subjects served as controls. Arterial elasticity of large and
      small arteries was evaluated using pulse wave contour analysis method (HDI CR
      200, Eagen, MN). Cardiac structure was assessed by two-dimensional
      echocardiography. We found decreased large artery elasticity in subclinical
      hyperthyroidism (sHT) patients compared to controls (14.14 +/- 3.38 versus 10.53
      +/- 2.43 L/mm Hg x 100, p < 0.000). Small artery elasticity was also lower in
      patients than in controls (5.42 +/- 1.82 versus 4.30 +/- 1.75 mL/mm Hg x 100, p <
      0.056). The echocardiographic data showed significantly increased left
      ventricular (LV) mass index (101.90 +/- 18.61 versus 88.03 +/- 22.01 g/m(2), p <
      0.049) and interventricular septum thickness (10.61 +/- 1.46 versus 9.11 +/- 1.13
      mm, p < 0.002) in LT(4)-treated patients compared to controls. CONCLUSIONS: We
      found impaired vascular elasticity of large and small arteries and increased LV
      mass in patients receiving long-term TSH-suppressive therapy with LT(4).

PMID- 16646686
TI  - Endocrine intervention during irradiation does not prevent damage to the thyroid
      gland.
AB  - Radiation to the head-neck region may damage the thyroid gland, leading to
      hypothyroidism or thyroid carcinoma. Outcomes of radiation protection by lowering
      plasma thyroid-stimulating hormone (TSH) have thus far been ambiguous. Our aim
      was to evaluate the radioprotective effect of inhibiting the thyroid gland's
      activity during x-radiation. For this purpose, of 80 5-week old Wistar rats, 64
      received cervical irradiation with 15 Gy (single dose). During irradiation,
      endocrine intervention was done, using thyroxine (T(4)), T(4) plus iodine, or
      iodine alone compared to placebo. During the endocrine interventions and follow
      up, TSH and T(4) concentrations were measured periodically. Histologic
      examination of thyroid, pituitary gland, or the hypothalamus and any suspect
      lymph nodes, lungs, and liver was performed after 6 and 54 weeks. It was found
      that during the endocrine intervention, plasma levels of TSH were lower in rats
      given T(4) and higher in rats given iodine. After 6 and 54 weeks, no significant
      reduction in hypothyroidism or thyroid carcinoma was found between the different
      groups of rats given any endocrine intervention or no intervention. In
      conclusion, the administration of T(4), iodine or the combination during x
      irradiation does not protect against radiation-induced thyroid damage.

PMID- 16646687
TI  - Effects of thyroid hormones on serum levels of adipokines as studied in patients
      with differentiated thyroid carcinoma during thyroxine withdrawal.
AB  - OBJECTIVE: Previous studies addressing the influence of thyroid hormones on serum
      levels of adipokines yielded conflicting results. We aimed to study the impact of
      short-term overt hypothyroidism on serum leptin, resistin, and adiponectin levels
      in an in vivo human model. DESIGN: Twenty-two women with differentiated thyroid
      carcinoma were studied the last day of their thyroxine-suppressive treatment, 4-7
      days after withdrawal, and the day before whole-body scanning. Evaluations
      included serum thyroid hormone, leptin, resistin, and adiponectin concentrations,
      fasting glucose and insulin, lipid profiles, body temperature, body mass index,
      and total body fat mass. MAIN OUTCOMES: Thyroid function changed from subclinical
      or mild hyperthyroidism to normal free thyroxine and triiodothyronine levels,
      ending in overt hypothyroidism. Thyroxine withdrawal resulted in an increase in
      serum resistin (p = 0.007) and leptin (p = 0.006) concentrations, whereas
      adiponectin levels remain unchanged. A significant decrease in body temperature
      during thyroxine withdrawal was paralleled by a decrease in fasting glucose (p =
      0.006) and insulin resistance (p = 0.033), which occurred despite an increase in
      estimated total body fat mass. CONCLUSION: Thyroid hormones are important
      regulators of energy balance and intermediate metabolism, influencing the serum
      concentrations of leptin and resistin.

PMID- 16646688
TI  - Pancytopenia in untreated patients with Graves' disease.
AB  - Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this
      report, we describe four patients with Graves' disease who presented with
      pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400
      mg/d) restored normal hematopoiesis in three of the patients. The remaining
      patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but
      had an increased peripheral blood count that almost reached normal values after
      radioiodinetherapy and standard immunosuppressive treatment with antithymocyte
      globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400
      mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150
      microg subcutaneous injection, 3 times per week). We conclude that: (1) a
      hematologic evaluation of all patients with Graves' disease should be performed
      before administering antithyroid drugs, (2) antithyroid drugs may be administered
      to patients with pancytopenia and bone marrow hypercellularity but a reevaluation
      of the bone marrow must be done if there is no recovery of the peripheral blood
      cell count when euthyroidism state is achieved, (3) standard immunosuppressive
      treatment of aplastic anemia caused by antithyroid drugs restores normal
      hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should
      be done, even though no related symptoms are found.

PMID- 16646689
TI  - Analysis of RET polymorphisms and haplotypes in the context of sporadic medullary
      thyroid carcinoma.
AB  - CONTEXT: Little is known about the etiology of sporadic medullary thyroid
      carcinoma (sMTC). While germline gain-of-function mutations in the RET proto
      oncogene cause hereditary MTC, the molecular mechanisms leading to the sporadic
      forms remain obscure. Our group had evidence about the existence of a low
      penetrance susceptibility locus for sMTC in linkage disequilibrium with RET
      variants S836S/IVS1-126G>T, and probably in 5' with respect to both variants. In
      this study we sought to identify such locus. On the other hand, because an
      overrepresentation of G691S/S904S variants in patients with sMTC had been
      previously reported, we sought to determine if such association was present in
      our series. DESIGN: We performed a case-control study analysing a wide spectrum
      of RET variants in the 5' region of the gene, as well as the variants
      G691S/S904S. Haplotype distribution were also analyzed. A total of 58 patients
      with sMTC were included in the study. In addition, 100 unselected, unrelated race
      , age-, and gender-matched normal controls were also evaluated. MAIN OUTCOME:
      Although the overrepresentation of IVS1-126G>T remains present in our current
      sMTC series, thus supporting our previous hypothesis, no differences were
      obtained among cases and controls in the distribution of the variants tested
      upstream this position. On the other hand, the frequency and distribution of
      G691S/S904S variants were similar in both groups of study, leading to exclude
      their role in sMTC in our series. CONCLUSIONS: These findings would suggest that
      the major genetic events contributing to the appearance of sMTC may reside in
      several different RET loci. In this way, we could hypothesize about the existence
      of at least two sMTC loci, linked to S836S-IVS1-126G>T, or to G691S-S904S,
      respectively.

PMID- 16646690
TI  - Imaging of inflammation in Graves' ophthalmopathy by positron emission
      tomography/computed tomography.

PMID- 16646691
TI  - Thyroid hematoma and infectious thyroiditis after a neck injury.

PMID- 16646693
TI  - A zero leak rate in 251 consecutive laparoscopic gastric bypass operations using
      a two-layer gastrojejunostomy technique.
AB  - PURPOSE: Laparoscopic Roux-en-Y gastric bypass is quickly replacing open
      techniques in the morbidly obese patient who presents for surgical treatment.
      Safety concerns about the laparoscopic technique have arisen in the literature
      with gastrojejunostomy leak rates of 5% or greater reported in several series.
      MATERIALS AND METHODS: A total of 251 consecutive gastric bypass operations were
      performed from August 2001 to January 2004 by a single surgeon with over 6 years'
      experience. A double layer technique was used for every gastrojejunostomy
      anastomosis. This consisted of end-to-side stapled anastomosis using only 30 mm
      of a 45 mm blue (3.5 mm) staple cartridge that was fired inside the gastric pouch
      and Roux limb. A posterior running suture was then used to reinforce the back
      wall. An intraluminal 32F bougie was placed before the stapler opening was
      closed. Finally, 2 running sutures were used to reinforce the anterior and
      lateral sides of the anastomosis. RESULTS: The average patient age was 43 years
      (range, 18-67 years), 89% were female, average preoperative weight was 137 kg
      (range, 89.5-214.5 kg), and average body mass index of 49 kg/m2 (range, 35-75).
      One hundred forty-two cases were performed with the Ethicon endoscopic linear
      stapler and 109 with the United States Surgical endoscopic linear stapler. There
      were no anastomotic leaks, staple line leaks, pulmonary emboli, or in-hospital
      deaths recorded. Endoscopic dilation successfully treated 10 (4%) cases of stomal
      stenosis. Eleven (4%) patients developed marginal ulcers that were easily treated
      with a proton pump inhibitor. Average excess weight loss at 12 months and 18
      months was 63% and 71%, respectively. CONCLUSIONS: Laparoscopic results are as
      good as or better than open surgery in the morbidly obese patient. The learning
      curve for this operation is steep and this may be reflected in the higher leak
      rates reported in earlier series. However, the technique used to create the
      gastrojejunostomy anastomosis may also account for a lower leak rate. The two
      layer gastrojejunostomy anastomotic technique combines an inner stapled layer and
      outer sutured layer that yields excellent results.

PMID- 16646694
TI  - Robotic assistant for laparoscopy.
AB  - BACKGROUND: With the advent of technologies allowing for wider application of
      minimally invasive surgeries, the integration of telerobotics for mentoring by a
      surgeon at a remote site will make it possible to include a wider audience in
      surgical consultations and collaboration. MATERIALS AND METHODS: Two surgery
      research fellows performed 8 laparoscopic cholecystectomies each in a swine
      model, as the animate portion of the study. Using the Zeus robotic system, a
      senior surgeon participated as a robotic assistant and consulted remotely.
      Teleconsultation was achieved using Hermes voice-activated software to display an
      on-screen pointer highlighting significant anatomic structures. To clarify the
      workspace space constraints on the robotic arms, an inanimate study was conducted
      to carry out retrieval, delivery, and complex object movement. RESULTS: All the
      laparoscopic cholecystectomies were completed successfully, with minimal blood
      loss and no complications. The robotic assistant surgeon participated in all
      surgeries and instructed on anatomical landmarks. The robotic tools were at a
      disadvantage due to the radius of movement. The simpler tasks were easier to
      complete than the complex movement, which required bimanual coordination.
      CONCLUSION: This study confirms the feasibility of integrating robotics as a
      surgical assistant and to consult distant audiences by a single senior surgeon.
      Incorporating remote access assistance and education capacities extends the
      limits of physical restrictions in completing surgical procedures safely.

PMID- 16646695
TI  - Effects of cognitive distraction on performance of laparoscopic surgical tasks.
AB  - HYPOTHESIS: To quantify the effects of cognitive distraction on surgical task
      performance in residents and medical students using a laparoscopic surgical
      simulator. DESIGN: Within-subjects design. SETTING: A surgical skills laboratory.
      PARTICIPANTS: Thirteen surgical residents and medical students who volunteered
      for the study. METHODS AND MATERIALS: Subjects performed six tasks on the
      Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR), under two
      different conditions (distracted and undistracted). Task order remained the same
      for all subjects, but the order of distraction was counterbalanced. In the
      distracted condition, distractions consisted of mental arithmetic problems posed
      sequentially so that subjects were continually distracted. MAIN OUTCOME MEASURES:
      Time to task completion, surgical errors committed, economy of motion, and
      overall performance scores were generated by the MIST-VR program software.
      Arithmetic error was not a factor in the overall performance score. RESULTS: Time
      to task completion was significantly greater when subjects were distracted for
      all six tasks performed. Overall score and economy of motion were negatively
      affected by distraction but the effect did not reach th level of statistical
      significance. There was no effect of distract on surgical errors. CONCLUSION:
      Cognitive distraction appears to negatively influence the performance of
      laparoscopic surgical tasks by increasing task completion time. Further study is
      required to determine what the effects would be on experienced surgeons and
      actual surgical outcomes.

PMID- 16646696
TI  - Survey of minimally invasive surgery fellowship programs.
AB  - INTRODUCTION: Since there was no accrediting body for minimally invasive surgery
      fellowships, this investigation was performed to characterize minimally invasive
      surgery fellowships. MATERIALS AND METHODS: All minimally invasive surgery
      fellowships that were noted on the Society of American Gastrointestinal
      Endoscopic Surgeons website in July 2002 were sent a survey. Only those
      fellowships that had fellow(s) for the year 2001-2002 were included in the
      survey. All programs were contacted a second time if the survey was not returned.
      Incomplete responses were not included in the data. RESULTS: There were 78
      fellowships listed, of which 16 had no fellow in 2001-2002, one which was not a
      minimally invasive surgery fellowship, and one which was listed twice. Of the 19
      (32%) programs that responded, there was an average of 1.3 clinical fellows per
      program (range, 1-3). All clinical fellowships were of one year duration. There
      was an average of 3.2 attendings for each program. Thirty-two percent of program
      directors had attended a laparoscopic fellowship. The average program received 50
      applications and interviewed 12 applicants for the year 2001-2002. The average
      fellow had 14 (range, 0-42) manuscripts, abstracts, and/or presentations either
      completed or in progress. Average minimally invasive cases performed was
      bariatric 95, colon 33, solid organ (liver, spleen, kidney, adrenal) 32,
      antireflux 36, hernia 54, and endoscopy 48. However, the range of these cases
      varied and the lowest number of cases for each category was bariatric 5, colon 3,
      solid organ 8, antireflux 1, hernia 6, and endoscopy 0. CONCLUSION: Minimally
      invasive surgery fellowships seem to be competitive for surgical residents. These
      fellowships vary in both research and clinical experience.

PMID- 16646697
TI  - Videolaparoscopic cholecystectomy for acute cholecystitis: analyzing conversion
      risk factors.
AB  - We examined a series of 176 consecutive patients scheduled for videolaparoscopic
      cholecystectomy for acute cholecystitis to identify the independent parameters
      most likely to lead to conversion to laparotomy. This prospective study was
      conducted from June 2001 to December 2003 on 176 consecutive patients who were
      scheduled for videolaparoscopic cholecystectomy for acute cholecystitis. Of the
      176 patients, 119 (group A) underwent videolaparoscopic chlecystectomy, and 57
      (32.3%) were converted to laparotomy (group B). Patients were assessed for
      gender, age, time between onset of symptoms and surgery, previous surgery, ASA
      (American Society of Anesthesia) risk, leukocytosis, echotomographic findings,
      average operating time, intra- and post-operative complications, and conversion
      rate. Our study found that the parameters of age, ASA risk, duration of symptoms,
      leukocytosis, and operative time are independent conversion risk factors.

PMID- 16646698
TI  - Intra-abdominal adhesions after open and laparoscopic cholecystectomy: an
      experimental model.
AB  - PURPOSE: To evaluate the incidence of intra-abdominal adherences after open and
      laparoscopic cholecystectomy, on the basis of an experimental study in pigs.
      MATERIALS AND METHODS: A total of 40 female pigs, mean weight 25 kg, underwent
      open cholecystectomy by right subcostal laparotomy (group A, n = 22) or
      laparoscopic cholecystectomy using a Storz laparoscope (group B, n = 18). After
      surgery, the abdominal wall was closed with polydioxanone suture and staples
      (group A) or with staples only (group B). One month later, the pigs underwent
      medial laparotomy to assess whether intra-abdominal adherences had developed.
      Incidences were compared between groups by the chi-square test with Yates
      correction. RESULTS: Five pigs in group A and one pig in group B died within 24
      hours of surgery, leaving 17 pigs in each group. Mean operative time was similar
      for both groups (24.7 minutes in group A, 25.3 minutes in group B). In group A,
      16 pigs (94%) developed intra-abdominal adherences, in all cases multiple; in
      group B, only 9 pigs (53%) developed adherences, and in 8 of these pigs only a
      single adherence was present (P < 0.03). CONCLUSIONS: The results of this study
      indicate that the incidence of intra-abdominal adherences is statistical lower
      after laparoscopic cholecystectomy than after open cholecystectomy.

PMID- 16646699
TI  - Role of appendectomy in laparoscopic training.
AB  - PURPOSE: This study aimed to evaluate whether laparoscopic appendectomy is
      suitable for training residents to become proficient in laparoscopic surgery.
      MATERIALS AND METHODS: A total of 1574 laparoscopic appendectomies were performed
      at En-Chu-Kong Hospital between January 1998 and December 2003 (788 men and 786
      women). These cases were divided into three groups: 543 cases (in 1998-1999)
      performed by 5 attending surgeons during the learning and trial stage; 536 cases
      (in 2000-2001) performed by 5 attending surgeons assisted by 2 senior residents
      with prior experience in open appendectomy; and 495 cases (in 2002-2003) done by
      these 2 senior residents, supervised by the attending surgeons. Demographic data,
      intraoperative findings, operative time, conversion rate, frequency of analgesic
      injection, timing of oral intake, hospital stay, morbidity, and mortality were
      analyzed. RESULTS: There were no statistically significant differences in the
      operations performed by attending surgeons (mature stage) vs. senior residents in
      terms of intraoperative findings, operative time (60.1 +/- 60.4 minutes vs. 56.3
      +/- 25.6 minutes), conversion rate (1.12% vs. 0.81%), frequency of analgesic
      injection (0.57 +/- 1.37 times/stay vs. 0.43 +/- 0.94 times/stay), timing of oral
      intake (23.7 +/- 30.2 hours vs. 20.8 +/- 27.5 hours), hospital stay (73.9 +/-
      61.8 hours vs. 70.3 +/- 51.6 hours), morbidity, or mortality (0% vs. 0.2%).
      CONCLUSION: Laparoscopic appendectomy can be safely incorporated into the
      training of surgical residents under the supervision of experienced surgeons.
      Laparoscopic appendectomy also provides knowledge of the basics of laparoscopic
      technique before going on to more complex operations.

PMID- 16646700
TI  - Long-term quality of life after laparoscopically assisted distal gastrectomy for
      gastric cancer.
AB  - OBJECTIVE: To investigate whether laparoscopically assisted distal gastrectomy
      (LADG) contributes to long-term quality of life as compared to open gastrectomy
      in patients with early-stage gastric cancer. MATERIALS AND METHODS: Quality of
      life was self-reported using a 15-item questionnaire with five options for each
      question. The responses obtained from 47 LADG patients and 33 conventional open
      gastrectomy patients were compared. All patients underwent Billroth I gastrectomy
      for early gastric cancer between September 1999 and October 2002. RESULTS:
      Patients who underwent LADG showed better results than those who underwent the
      open procedure with regard to satisfaction with the operation (87.2% vs. 57.6%; P
      < 0.01). However, the rate of late complications such as delayed gastric emptying
      was higher in the LADG group than in the open group (40.4% vs. 18.2%; P < 0.05).
      No differences were observed between the LADG and open groups with regard to
      appetite loss, heartburn, diarrhea, or difficulty in swallowing. CONCLUSION: LADG
      has an equivocal effect on long-term quality of life. Satisfaction with the
      surgical procedure was greater in patients who underwent the LADG method;
      however, complications that impaired the quality of life were also seen. The
      usefulness of LADG should be assessed in view of the immediate and relatively
      short-term outcomes and their effect on long-term quality of life.

PMID- 16646701
TI  - Role of fundus-first laparoscopic cholecystectomy in the management of acute
      cholecystitis in elderly patients.
AB  - BACKGROUND: Conversion from laparoscopic cholecystectomy to open cholecystectomy
      leads to the loss of the advantages of this minimally invasive procedure and
      significantly increases length of hospital stay as well as cost. The conversion
      from laparoscopic to open cholecystectomy is more frequent among patients with
      acute cholecystitis and in elderly patients. This study evaluated whether fundus
      first laparoscopic cholecystectomy could lower the conversion rate in geriatric
      patients with acute cholecystitis. MATERIALS AND METHODS: During a twelve-month
      period, 112 patients (36 of them age 65 years or older) underwent fundus-first
      laparoscopic cholecystectomy for acute cholecystitis in a tertiary care
      university hospital in central Taiwan. RESULTS: The conversion rate in the
      elderly patients was 2.7% (1/36). No major perioperative complications were
      observed. Minor complications--port-site infection and subhepatic fluid
      collection-occurred in two patients (5.5%). CONCLUSION: Laparoscopic
      cholecystectomy with a fundus-first approach is a safe, effective operative
      procedure for elderly patients with acute cholecystitis when performed by an
      experienced laparoendoscopic surgeon.

PMID- 16646702
TI  - Splenic retrieval after laparoscopic splenectomy: a new bag.
AB  - BACKGROUND: Laparoscopic splenectomy has become the gold-standard surgical
      approach for patients undergoing elective splenectomy. Little data exist
      concerning the technical difficulties of splenic retrieval. When the spleen is
      large, popular commercial retrieval bags are often too small to facilitate
      removal. The aim of this study was to compare our clinical experience utilizing
      two different retrieval bags, the Endocatch II (Autosuture, London, UK) and the
      developing E200 (Espiner Ltd., Bristol, UK). MATERIALS AND METHODS: We performed
      a retrospective review of all laparoscopic splenectomies performed at Hull Royal
      Infirmary, Kingston upon Hull, from March 1997 to July 2003. Patient
      demographics, morbidity, mortality, and clinical outcome had been entered
      prospectively into a database. Two patient groups were examined, depending on the
      type of retrieval bag utilized. Complications and instrument failure during
      splenic retrieval were analysed. RESULTS: A total of 83 laparoscopic
      splenectomies were performed. No retrieval bag was used in 8 cases (10%). The
      Endocatch retrieval bag was used for 45 (60%) patients and the E200 for 30 (40%)
      patients. The mean operative time for the former group was 65 minutes (range, 50
      127 minutes) and for the latter, 120 minutes (range, 80-180 minutes) (P < 0.05).
      Bag-related complications were 2 (4%) perforations and 2 (4%) failures to deploy
      while using the Endocatch bag. CONCLUSION: The Endocatch bag is easy to deploy
      but is associated with perforation and cannot be used for large spleens. The E200
      bag is more useful for large spleens but is associated with prolonged operative
      time due to poor maneuverability. Improved technology is still required.

PMID- 16646703
TI  - Palliative gastrojejunostomy for advanced gastric antral cancer: double scope
      technique.
AB  - Gastrojejunostomy through laparotomy is a traditional procedure for the relief of
      gastric outlet obstruction in patients with unresectable carcinoma of the gastric
      antrum. However, patients face pain and high rates of morbidity and mortality
      after this operation. We present two cases of gastrojejunostomy for unresectable
      and obstructing gastric antral cancer using a double scope technique. The
      operative time was approximately 90 minutes for each patient, and the
      postoperative hospital stays were 9 and 10 days, respectively. Operative results
      were good. Vomiting was relieved. There were no delays in gastric emptying. No
      recurrence of gastric outlet obstruction was noted in the first patient, who died
      9 months postoperatively. The second patient survived without this problem 6
      months postoperatively. Palliative gastrojejunostomy via the double scope
      technique is a safe and effective minimally invasive procedure for the relief of
      gastric outlet obstruction in patients with unresectable carcinoma of the gastric
      antrum. It also provides accurate staging of the disease perioperatively. It
      should be considered the surgical choice for geriatric patients when clinically
      appropriate.

PMID- 16646704
TI  - Laparoscopic diagnosis and treatment of small bowel obstruction caused by
      postoperative intussusception.
AB  - Small bowel obstruction is a common problem, especially for patients who have had
      previous abdominal surgery possibly complicated by postoperative adhesions. In
      contrast to adhesions, postoperative intussusception is an unusual cause of small
      bowel obstruction. We report a case of small bowel obstruction that occurred one
      month after antrectomy for duodenal ulcer with massive bleeding. Laparoscopic
      surgery was attempted after conservative treatment failed. A segment of
      jejunojejunal intussusception about 50 cm below the ligament of Treitz was
      identified and laparoscopic reduction of the intussusception was performed. The
      patient had an uneventful postoperative course and remained asymptomatic at 10
      month follow-up. Although not frequently encountered, postoperative
      intussusception should be considered a possible etiology in patients with
      postoperative small bowel obstruction. In experienced hands, the laparoscopic
      approach offers a feasible option for correct diagnosis and appropriate treatment
      in this situation.

PMID- 16646705
TI  - Laparoscopic harvest of an omental flap to reconstruct an infected sternotomy
      wound.
AB  - Sternotomy dehiscence is associated with a high mortality rate. In most cases
      this complication may be treated by simple debridement and antibiotic therapy,
      but sometimes it is necessary to fill the sternal defect with viable tissue. The
      greater omentum seems to be the ideal tissue to be transposed because of its
      malleability, good vascularization, and high lymphatic tissue content. The
      transposition of the greater omentum usually requires a midline laparotomy for
      the preparation of the flap, with significant laparotomy-related morbidity.
      Laparoscopic access may represent an effective alternative for preparing and
      transposing the omental flap. The key points of the laparoscopic technique are
      (1) the coloepiploic detachment, (2) the section of the anastomotic arterial
      branches between the Barkow's arcade and the gastroepiploic arcade, (3) the
      mobilization of the greater omentum pedicled on the right gastroepiploic artery,
      and (4) its transposition into the mediastinum, taking care to avoid twisting the
      gastric greater curvature and the flap itself.

PMID- 16646706
TI  - Laparoscopic intragastric surgery using GelPort.
AB  - In laparoscopic intragastric surgery for early gastric cancer and submucosal
      tumors, three trocars are routinely inserted in the gastric lumen. We placed a
      GelPort hand assist device through a 5-cm transverse incision in the upper
      abdomen, and inserted the trocars into the gastric lumen through the gel seal
      cap, snapping the gel seal cap on and off during the operation. This makes it
      possible to use an open technique in which trocars are inserted into the gastric
      lumen, and to close the trocar sites in the gastric wall. We believe that the
      technique described here is easier and saves time compared with inserting trocars
      and closing trocar sites laparoscopically.

PMID- 16646707
TI  - Differential response of arteries and veins to bipolar vessel sealing: evaluation
      of a novel reusable device.
AB  - BACKGROUND: A variety of energy-based techniques for arterial and venous vessel
      ligation have recently been introduced. Using a porcine model we studied the
      efficacy of the novel reusable BiClamp versus the standard disposable LigaSure
      bipolar vessel sealing device. We also compared whether arteries respond
      differently than veins upon sealing. MATERIALS AND METHODS: In five Swabian Hall
      pigs, splenectomy and nephrectomy were performed using two different bipolar
      vessel sealing devices. Measurements of the sealed arteries and veins (diameter 2
      7 mm) included rate of seal failure, burst strength, and heat-associated vascular
      wall morphologic appearance. An additional three animals underwent splenectomy,
      salpingo-oophorectomy, and small bowel resection, and vessel seals were studied
      histologically after a seven-day survival period for vessel wall fusion,
      inflammation, and fibrous organization. RESULTS: Sealing was highly successful,
      with only one seal failure overall and thus no difference between the two
      instruments analyzed. The burst pressures of BiClamp-sealed arteries (842 +/- 117
      mm Hg) did not differ from that of arteries sealed with LigaSure (856 +/- 102 mm
      Hg), but were significantly higher than the burst pressures of veins (155 +/- 26
      and 216 +/- 71 mm Hg, respectively) (P < 0.05). Independent of the sealing device
      used, thermal spread was found increased in veins compared to arteries.
      Histologic analysis after seven days revealed appropriate healing of the vessel
      wall, including thrombus fibrosis, fibroblast proliferation, and collagen
      deposition. With both devices, however, the venous but not the arterial walls
      still presented with massive inflammatory cell infiltrates. CONCLUSION: Our study
      indicates that the BiClamp device is as appropriate as the LigaSure instrument to
      successfully ligate 2-7 mm arteries and veins, demonstrating supraphysiological
      bursting strengths and adequate lumenal fusion healing. However, veins are more
      prone to collateral tissue damage and inflammatory wall infiltration.

PMID- 16646708
TI  - Physiological effects of pneumoperitoneum in laparoscopic pyloromyotomy.
AB  - A retrospective analysis comparing intraoperative physiological variables during
      laparoscopic and open pyloromyotomies was undertaken during an 18-month period at
      our institution. Fifty cases were examined (22 laparocopic and 28 open).
      Operative time, temperature change, end-tidal CO2, heart rate, and blood pressure
      were examined and compared. No significant differences were found in operative
      time, temperature change, heart rate, and blood pressure. As anticipated, in
      laparoscopic procedures there was a statistically significant increase in end
      tidal CO2, although none of the end-tidal CO2 values rose above 6 kPa. It is
      concluded that laparoscopic pyloromyotomies undertaken in small infants with
      insufflation pressures of 8-10 mm Hg are without significant adverse
      physiological effects and are no slower to perform than open procedures.

PMID- 16646709
TI  - Laparoscopic appendectomy in children with perforated appendicitis.
AB  - PURPOSE: There is persistent controversy regarding the optimal surgical therapy
      for children with appendicitis. We have recently adopted laparoscopic
      appendectomy in lieu of the open technique for children with perforated
      appendicitis. We hypothesized that laparoscopic appendectomy would be as
      effective as open appendectomy in preventing postoperative complications.
      MATERIALS AND METHODS: We reviewed the medical records of children admitted to
      our hospital over a 5-year period with the diagnosis of perforated appendicitis.
      Patients were divided into two groups based on the operative approach:
      laparoscopic vs. open appendectomy. Demographic data, duration of presenting
      symptoms, initial white blood cell (WBC) count, length of stay, and complications
      were abstracted. Data were compared using appropriate statistical analyses.
      RESULTS: There was no difference between the laparoscopic (n = 43) and open (n =
      77) groups with respect to gender, duration of presenting symptoms, initial WBC,
      or length of stay. However, patients in the laparoscopic group had a
      significantly lower complication rate than those in the open group (6/43 vs.
      23/77, P = 0.05). Infectious complications were no different between groups.
      Patients in the laparoscopic group tended to be older than patients in the open
      group (10.6 +/- 3.3 years vs. 8.5 +/- 4.1 years, P = 0.003). CONCLUSION:
      Laparoscopic appendectomy for children with perforated appendicitis has the same
      infectious complication rate and a lower overall complication rate than open
      appendectomy. A prospective study with standardized postoperative care would be
      needed to determine whether laparoscopic appendectomy for children with
      perforated appendicitis is the treatment of choice, but until then it remains an
      attractive alternative.

PMID- 16646710
TI  - Nonoperative correction of pectus carinatum with orthotic bracing.
AB  - BACKGROUND: This study sought to evaluate the efficacy of nonoperative
      compression in correcting pectus carinatum in children. MATERIALS AND METHODS:
      Children presenting with pectus carinatum between August 1999 and January 2004
      were prospectively enrolled in this study. The management protocol included
      custom compressive bracing, strengthening exercises, and frequent clinical follow
      up. RESULTS: There were 30 children seen for evaluation. Their mean age was 13
      years (range, 3-16 years) and there were 26 boys and 4 girls. Of the 30 original
      patients, 6 never returned to obtain the brace, leaving 24 patients in the study.
      Another 4 subjects were lost to follow-up. For the remaining 20 patients who have
      either completed treatment or continue in the study, the mean duration of bracing
      was 16 months, involving an average of 3 follow-up visits and 2 brace
      adjustments. Five of these patients had little or no improvement due to either
      too short a follow-up or noncompliance with the bracing. The other 15 patients
      (75%) had a significant to complete correction. There were no complications
      encountered during the study period. CONCLUSION: Compressive orthotic bracing is
      a safe and effective alternative to both invasive surgical correction and no
      treatment for pectus carinatum in children. Compliance is critical to the success
      of this management strategy.

PMID- 16646711
TI  - Laparoscopic antegrade continence enema using a two-port technique.
AB  - BACKGROUND: The antegrade continence enema is an effective method of treatment of
      fecal incontinence. We report our experience of a laparoscopic antegrade
      continence enema procedure and describe a simple approach to this procedure using
      a two-port technique. MATERIALS AND METHODS: Over a 3-year period, 12 children
      with intractable constipation and fecal soiling underwent the antegrade
      continence enema procedure laparoscopically. All cases had full bowel preparation
      the day before surgery. This procedure was done through one 5-mm camera port and
      two 5-mm working ports in 8 cases, and using the camera port and only one
      additional 5-mm working port in 4 cases. The appendix was used in 5 cases and the
      cecum in 3 cases with the threeport technique while the appendix was used in all
      4 cases with the two-port technique. The appendix or cecum was delivered
      extracorporeally through the 5-mm port site in the right lower quadrant. The
      mucocutaneous anastomosis was stented using a gastrostomy button. RESULTS:
      Between 2001 and 2004, 12 children (10 male, 2 female) underwent a laparoscopic
      antegrade continence enema procedure at a median age of 10.5 years (range, 7-14
      years). This procedure was easy to perform and no case required conversion to an
      open procedure. The wash-outs via the MIC-KEY gastrostomy button (MIC-KEY,
      Kimberly-Clark) were commenced at a median of 3.5 days (range, 1-5 days). Median
      postoperative hospital stay was 2 days (range, 1-5 days). This procedure was
      effective in completely resolving fecal incontinence in 9 cases and partially
      resolving it in 3 cases. There were no episodes of stomal stenosis, leakage, or
      herniation. However, one case required a revision of antegrade continence enema
      due to wound breakdown and leakage of irrigation fluid around the stoma. The
      median follow-up period was 15.5 months (range, 5-32 months). CONCLUSION: The
      laparoscopic technique is a simple and effective approach in creating an
      antegrade continence enema. The use of a gastrostomy button can potentially
      reduce some of the complications commonly associated with an antegrade continence
      enema. We describe a procedure that incorporates the advantages of both
      laparoscopy and a button device, which is simple and easy to perform using just
      two ports.

PMID- 16646712
TI  - Thoracoscopic repair of esophageal atresia and tracheoesophageal fistula: lessons
      learned.
AB  - OBJECTIVE: Repair of esophageal atresia and tracheoesophageal fistula has
      traditionally been performed via thoracotomy. This study aims to evaluate the
      feasibility and pitfalls of the thoracoscopic approach. MATERIALS AND METHODS:
      Six consecutive patients with type C tracheoesophageal fistulae underwent
      thoracoscopic repair. The operation was approached through the right chest using
      a three-trocar technique (two 5-mm and one 3-mm) with the patient placed in a
      three-quarter prone position. Patient characteristics, operative time, duration
      of narcotic usage, conversion factors, postoperative complications, and long-term
      follow-up were recorded. RESULTS: Five of six patients were successfully operated
      on thoracoscopically. The average operative time was 143 minutes (range, 75-215
      minutes) with repair of long-gap defects requiring significantly longer times
      than short-gap defects (200 vs. 129 minutes, P < 0.05). There were no
      intraoperative complications. Mean duration of narcotic use was 52 hours (range,
      24-72 hours). There were no anastomotic leaks. One patient developed an
      anastomotic stricture at the third postoperative week, which resolved with two
      dilations. One patient died on the first postoperative day from respiratory
      failure. CONCLUSION: Thoracoscopic repair of esophageal atresia and
      tracheoesophageal fistula is feasible, but is technically challenging. Long-gap
      defects require more extensive dissection and difficult anastomosis, and are
      therefore associated with longer operative times. More data are needed for
      further evaluation of this approach.

PMID- 16646713
TI  - Robot-assisted laparoscopic resection of a type I choledochal cyst in a child.
AB  - Although the laparoscopic approach to the treatment of complex biliary disease is
      possible, it is technically challenging. In an attempt to overcome these
      difficulties, the da Vinci Surgical System (Intuitive Surgical, Sunnyvale,
      California) was used to facilitate the minimally invasive treatment of a type I
      choledochal cyst in a 5-year-old, 22 kg, girl. Complete resection of the
      choledochal cyst and a Roux-en-Y hepaticojejunostomy were performed using the
      robotic surgical system. Total robotic setup time (preparation, port placement,
      docking) was 40 minutes. Total procedure time was 440 minutes. Total robotic
      operative time was 390 minutes. No intraoperative complications or technical
      problems were encountered. At 6-month follow-up, the child is doing well with no
      episodes of cholangitis. Robot-assisted laparoscopic type I choledochal cyst
      resection appears safe and feasible. The three-dimensional visualization and
      wristed instrumentation greatly aids in the dissection of the cyst and in the
      biliary reconstruction.

PMID- 16646714
TI  - Combined use of preoperative methylene blue dye and microcoil localization
      facilitates thoracoscopic wedge resection of indeterminate pulmonary nodules in
      children.
AB  - The ability to biopsy indeterminate pulmonary lesions in children has evolved
      with advances in minimal access surgery. Recent advances in preoperative
      localization including image-guided dye injection or wire implantation have
      expanded the types of lesions that are accessible via minimal access surgery. We
      present a case of a 13-year-old boy who underwent preoperative localization using
      both methylene blue dye and microcoil labeling, and a subsequent thoracoscopic
      pulmonary wedge resection under the same anesthesia. The combined use of both dye
      and microcoil localization provides the advantage of superior intraoperative
      visualization of the lesion and the ability to use fluoroscopy to confirm the
      presence of the nodule in the surgical specimen. We recommend this technique for
      the biopsy of indeterminate pulmonary lesions that would not otherwise be
      accessible via a minimally invasive approach.

PMID- 16646715
TI  - A simple and secure method to fix laparoscopic trocars in children.
AB  - We introduce a simple method of fixing trocars to the abdominal wall in children.
      Before anchoring the trocar, a piece of Tegaderm polyurethrane adhesive (3M
      Healthcare, St. Paul, Minnesota) is attached to the trocar. A silk stitch is
      anchored to neighboring skin, and then transfixed over the shaft of the trocar
      through the adhesive. Both inward and outward movement of the trocar can be
      restrained. This method is simple, fast, secure, and can be applied to trocars of
      any size.

PMID- 16646720
TI  - The Swiss program for the evaluation of complementary medicine (PEK).

PMID- 16646721
TI  - Attitudes and intentions of patients toward integrated Chinese and Western
      medicine in Taiwan.

PMID- 16646722
TI  - Designing an acupuncture study: the nationwide, randomized, controlled, German
      acupuncture trials on migraine and tension-type headache.
AB  - BACKGROUND: In the nationwide German Acupuncture Trials (GERAC) verum
      acupuncture, based on Traditional Chinese Medicine (TCM), was to be tested
      against sham acupuncture for the entities classified in the West as "migraine"
      (MIG) and "tension-type headache" (TTH). However, there were no generally
      accepted guidelines on how to perform a consistent verum or sham treatment.
      OBJECTIVE: To design broadly consensual verum and sham acupuncture treatment
      protocols for MIG and TTH for the GERAC. METHODOLOGY: Extensive literature study
      and consultation with acupuncture experts. Personal interviews, both free and
      structured, e-mail discussions, and phone conferences were used. RESULTS: Broadly
      consensual acupuncture protocols for MIG and TTH for verum and sham acupuncture
      were developed. They included semi-standardized point combinations with clearly
      described point selection rules based on TCM acupuncture diagnoses. A procedure
      was developed to help ensure homogenous treatment quality in a large multicenter
      trial. CONCLUSIONS: The GERAC study design allowed acupuncture to be tested in a
      naturalistic environment. The rigorous study design and the large number of
      physician investigators guaranteed a high external validity for the results. The
      results will help determine the significance of Chinese acupuncture in the
      context of Western medicine for the treatment of MIG and TTH.

PMID- 16646723
TI  - Exploring outcomes associated with acupuncture.
AB  - OBJECTIVE: The objective was to explore various methods of assessing clinically
      meaningful change associated with a course of acupuncture treatments. DESIGN: The
      design was a prospective cohort study. SETTING: The setting was an acupuncture
      clinic staffed by two physician acupuncturists in a university-affiliated family
      practice center. SUBJECTS: Subjects consisted of consecutive new patients to an
      acupuncture clinic. OUTCOME MEASURES: Outcomes were measured using the Medical
      Outcomes Study Short-Form 36 (SF-36) and Measure Your Own Medical Outcomes
      Profile (MYMOP). Outcomes measured were global clinical change and patient
      satisfaction. RESULTS: Out of 112 eligible patients, 110 consented to the study
      and contributed baseline data. Of these, 80 (71%) completed the 2-month follow-up
      questionnaire. Mean age of study subjects was 54.5 (standard deviation, SD 17.6)
      years; 85 (77%) were female, and 75 (68%) were married. Mean number of
      acupuncture treatments during the 2-month follow-up period was 5.8 (SD, 3.5,
      range, 1 to 16). Statistically significant improvement from baseline to follow-up
      was observed with the bodily pain subscale of the SF-36 and with the MYMOP. Among
      those who completed the study, 52 (67%) felt that the main symptom for which they
      sought acupuncture had improved over the course of the study and 72 (90%) were
      satisfied with their treatment in the acupuncture clinic. CONCLUSIONS: The MYMOP
      instrument appears to be the most useful of the four measures used to evaluate
      clinical outcomes associated with a course of acupuncture treatments (SF-36,
      MYMOP, global clinical change, and patient satisfaction). This easy-to-administer
      instrument appears to be sensitive to clinical change over a 2-month period among
      patients who sought acupuncture for a wide variety of clinical conditions.

PMID- 16646724
TI  - Applying evidence-based medicine to traditional chinese medicine: debate and
      strategy.
AB  - Drawing on recent paper published literature in both English and Chinese, this
      explores reactions to the evaluation of Chinese medicine using randomized
      controlled trials (RCTs) and the standards of evidence-based medicine (EBM). The
      literature review revealed a few sources which contend that Chinese medicine
      should not be evaluated on the basis of RCTs, but a far greater number which
      advocate for applying RCT and EBM standards to Chinese medicine. This paper
      describes the position of the detractors and points out ways in which their
      arguments contain oversimplified representations of Chinese medicine,
      biomedicine, EBM, and RCTs. In describing the position of the proponents, the
      analysis outlines some of the numerous innovative techniques they are developing
      for dealing with issues of control and standardization in efficacy research.
      Overall, the analysis indicates that important refinements are being generated in
      Chinese medicine research and clinical trial design in response to the challenges
      posed by the forced encounter of these two paradigms.

PMID- 16646725
TI  - Reactive oxygen species (ROS): pathogens or sources of vital energy? Part 2.
      Bioenergetic and bioinformational functions of ROS.
AB  - In Part 1 of the review of experimental data concerning reactive oxygen species
      (ROS) production and use, their indispensable role in regulation of multiple
      physiologic processes is examined. Part 2 considers the unique property of
      reactions in which ROS participates, the generation of energy of electronic
      excitation (EEE). Because of incessant ROS cycling, EEE is continuously produced
      in aerobic organisms. It may be used as an energy activator for multiple
      biochemical reactions and also may function as a specific signaling factor. This
      approach allows the perception of the beneficial effects of hydrogen peroxide,
      ozone, other ROS therapy, and foods rich in antioxidants. Both insufficient
      production of ROS and distortions in their use may cause anomalies in
      coordination of ROS generation and use, resulting in the deranged operation of
      biochemical and physiologic processes and the development of pathology.

PMID- 16646726
TI  - Entanglement, knowledge, and their possible effects on the outcomes of blinded
      trials of homeopathic provings.
AB  - INTRODUCTION: In two recent studies of double-blind placebo-controlled
      homeopathic provings, entanglement was reported to have occurred between verum
      and placebo arms of the trials. This contrasts directly with the entanglement
      disrupting effects of blinding, recently proposed as the reason for the failure
      of randomized controlled trials (RCTs) to demonstrate unequivocally the efficacy
      of homeopathy. It is proposed here that such entanglement between remedy and
      placebo during these double-blind placebo controlled provings is the direct
      result of the blinding process. METHOD: A previously developed theoretical model
      of entanglement in homeopathy among patient, practitioner, and remedy (called PPR
      entanglement) was used in this investigation. RESULTS: In agreement with the
      results from the proving studies, the model predicts that application of the
      double-blind RCT methodology to homeopathic provings leads to entanglement
      between both remedy and placebo arms of the trial. CONCLUSIONS: These theoretical
      findings can be understood in terms of the act of blinding leading to loss of
      information because of quantum-like state superposition of the verum and placebo
      proving groups. This is compared to conclusions drawn from the well-known double
      slit experiment of quantum physics, and quantum information processing. It leads
      to a suggestion for testing entanglement in homeopathic provings.

PMID- 16646727
TI  - Variation in complementary and alternative medicine (CAM) use across
      racial/ethnic groups and the development of ethnic-specific measures of CAM use.
AB  - OBJECTIVES: The use of complementary and alternative medicine (CAM) is likely to
      vary among racial/ethnic groups because its use is related to cultural and health
      beliefs. Understanding patterns of CAM use among ethnic groups could inform
      clinical practice and the study of CAM use in a diverse population. The authors
      compared CAM use among Asian-Americans, American Indians, African Americans,
      Latinos, whites, and other racial/ethnic groups in order to develop ethnic
      specific measures of CAM use and explore factors associated with such CAM use
      across ethnic groups. DESIGN: A cross-sectional survey of a sample of 9187 adults
      representative of the California population was performed. OUTCOME MEASURES:
      Ethnic-specific constructs for Asian-Americans, American Indians, African
      Americans, Latinos, and whites were devised. RESULTS: The authors identified
      ethnic-specific CAM modalities for each ethnic group. Demographic and clinical
      factors associated with use of ethnic-specific CAM differed from the predictors
      of overall CAM use in the general population and varied by ethnicity.
      CONCLUSIONS: Patterns of CAM use and ethnic-specific CAM use vary across
      racial/ethnic groups. Evaluation of CAM use in ethnically diverse populations
      should recognize ethnic-specific modalities and variation across ethnicity.

PMID- 16646728
TI  - Pediatric patients with sickle cell disease: use of complementary and alternative
      therapies.
AB  - OBJECTIVE: Despite clinical advances, sickle cell disease (SCD) remains a
      difficult, chronic medical condition for many children and youth. Additional
      treatment strategies, including complementary and alternative medicine (CAM)
      therapies, would be welcome to enhance the clinical care of SCD patients. This
      study's objective was to identify CAM therapies that are currently used by
      families for children with SCD, and to investigate SCD families' interest in CAM.
      PATIENTS AND METHODS: Fifty-seven (57) parents of pediatric SCD patients
      participated in this cross-sectional telephone survey in early 2000. A SCD
      Severity Scale was developed by combining the general health assessment and four
      measures of SCD severity (Cronbach's alpha = 0.81). RESULTS: Fifty-four percent
      (54%) of the sample used CAM therapies for the SCD children. Forty-two percent
      (42%) used bioenergetic therapies (prayer, spiritual and energy healing), 28%
      used lifestyle/mind?body CAM (relaxation techniques, exercise, imagery, and
      diet), 12% used biochemical therapies (herbal medicines, megavitamins, and folk
      remedies), and 5% used biomechanical therapy (massage). CAM use for the SCD
      children was positively associated with the child's age, SCD Severity Scale
      score, respondent education, and respondent CAM use. The use of relaxation
      techniques was associated with greater SCD severity. Most respondents (83%) felt
      that CAM can be helpful. CONCLUSIONS: The use of CAM therapies is common for
      children with SCD. Prayer, relaxation techniques, and spiritual healing were the
      most commonly reported CAM therapies. Because clinical studies have shown the
      benefit of spiritual and relaxation practices for SCD and this study shows that
      these CAM therapies are being used commonly by SCD families, future research
      should focus on spiritual and relaxation practices for children with SCD.

PMID- 16646729
TI  - Screening of antihelminthic effects of Indian plant extracts: a preliminary
      report.
AB  - INTRODUCTION: The purpose of the present study was to evaluate the antihelminthic
      effect of plants from the Ayurvedic system of medicine traditionally used in
      India. MATERIALS AND METHODS: Six plant extracts were assayed for their activity
      against free-living nematodes. Inhibitory effects on free-living nematodes were
      evaluated in vitro using aqueous or ethanolic extracts. CONCLUSIONS: Of six
      plants assayed, Momordica charantia yielded the best results, its crude extract
      producing 96% mortality.

PMID- 16646730
TI  - A review and analysis of placebo treatments, placebo effects, and placebo
      controls in trials of medical procedures when sham is not inert.
AB  - Researchers examining the efficacy of medical procedures make assumptions about
      the nature of placebo. From these assumptions they select the sham interventions
      to be used in their trials. However, placebo is not well defined. A number of
      definitions are contradictory and sometimes misleading. This leads to problems in
      sham-controlled studies of medical procedures and difficulties interpreting their
      results. The author explores some of the contradictory definitions of placebo and
      assumptions and consequences of these. Principal among these is the assumption
      that the placebo is inert when it is not, which introduces bias against the
      tested medical procedures and devices. To illustrate the problem, the author
      examines the use of sham procedures in clinical trials of the medical procedures
      surgery and acupuncture in which the sham was assumed to be inert but was not.
      Trials of surgery and acupuncture should be re-examined in light of this.

PMID- 16646731
TI  - Complete remission achieved in a case of both primary and recurrent adult acute
      myelogeneous leukemia by a novel nutritional therapy.
AB  - OBJECTIVES: The aim of this study was to determine the possible clinical benefit
      of molasses-based dietary compositions (designated as MSQ 13, MSQ 15, and MSQ 18)
      in a case of both primary and recurrent adult AML. DESIGN: The design was a
      single case study. SETTINGS/LOCATION: The setting was in the home. INTERVENTIONS:
      The regime of dietary compositions initially was administered as follows: MSQ-13
      1 tbsp t.i.d. for 1 mo, MSQ-15 2 tbsp t.i.d. for 3 mo. After recurrence, MSQ-18
      was taken at 2 tbsp t.i.d. for 3 mo. OUTCOME MEASURES: Clinical improvement and
      regression of AML were the outcome measures. CONCLUSIONS: Treatment with the MSQ
      dietary compositions resulted in disease regression and the reversal of clinical
      manifestations over two episodes of AML. Therefore, further studies are warranted
      to evaluate the utility of this approach for the clinical management of AML.

PMID- 16646732
TI  - Adolescent endometriosis-related pelvic pain treated with acupuncture: two case
      reports.
AB  - BACKGROUND: Chronic pelvic pain in adolescents accounts for 10% of outpatient
      gynecology visits, and 70% of adolescent patients whose pelvic pain is
      unresponsive to initial therapy have endometriosis. To date, there has been no
      published research investigating the use of acupuncture for adolescents with
      chronic pelvic pain and/or endometriosis. METHODS: This paper presents two case
      reports describing the impact of a course of acupuncture on adolescent girls with
      endometriosis-related chronic pelvic pain of more than 1 year. RESULTS: Both
      patients, undergoing between 9 and 15 treatments over a 7- to 12-week period,
      experienced modest improvement in pain as measured by oral self-reports of pain
      on a scale from 1 to 10, as well as self or family-reported improvement in
      headaches, nausea and fatigue. No adverse effects were reported. CONCLUSIONS:
      These case reports provide preliminary evidence that acupuncture may be an
      acceptable and safe adjunct treatment therapy for some adolescents with
      endometriosis-related pelvic pain refractory to standard antiendometriosis
      therapies. These observations suggest that a prospective, randomized controlled
      trial of the safety and efficacy of acupuncture for this population may be
      warranted.

PMID- 16646733
TI  - Evidence-based medicine and naturopathy.
AB  - Evidence-based medicine (EBM) has been advocated as a new paradigm in orthodox
      medicine and as a methodology for natural medicines, which are often accused of
      lacking an adequate scientific basis. This paper presents the voices of tradition
      sensitive naturopathic practitioners in response to what they perceive as an
      ideologic assault by EBM advocates on the validity and integrity of natural
      medicine practice. Those natural medicine practices, which have tradition-based
      paradigms articulating vitalistic and holistic principles, may have significant
      problems in relating to the idea of EBM as developed in biomedical contexts. The
      paper questions the appropriateness of imposing a methodology that appears to
      minimize or bypass the philosophic and methodological foundations of natural
      medicine, and that itself seems primarily driven by political considerations.

PMID- 16646734
TI  - Status of credentialing alternative providers within a subset of U.S. academic
      health centers.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) clinical services are
      increasingly provided within conventional health care settings. OBJECTIVE: To
      determine how a subset of U.S. academic health centers is credentialing CAM
      providers. DESIGN: An electronic survey was created focusing on the credentialing
      method utilized for six specific types of CAM clinical practitioners within
      academic medical settings. METHODS: This survey was electronically distributed to
      33 academic health centers in the United States during the summer 2004. RESULTS:
      Ninety-five percent (95%) of academic centers surveyed provide some CAM clinical
      care. Acupuncture and massage are most common, with naturopathy and homeopathy
      least common. State licensure requirements for CAM providers appear to not be
      well-understood. Most commonly, CAM professionals do not receive full medical
      staff credentials. LIMITATIONS: Results cannot be extrapolated to remaining
      academic health centers within the United States. Mind-body practitioners were
      not included in the survey. CONCLUSIONS: Credentialing and privileges are most
      commonly granted via indirect methods. Variability in state licensure compounds
      the challenge of credentialing CAM practitioners. Suggestions for beginning
      discussions on guiding principles for integrating CAM practitioners within
      conventional settings are proposed.

PMID- 16646735
TI  - Harmonizing the cacophony: commentary on "Status of credentialing alternative
      providers within a subset of U.S. academic health centers".

PMID- 16646736
TI  - The naturopathic medical research agenda: the future and foundation of
      naturopathic medical science.

PMID- 16646737
TI  - Summary consensus statement of the PEK review board regarding the PEK process and
      the PEK products.

PMID- 16646738
TI  - Improving acute care services for older people.

PMID- 16646739
TI  - Lung transplantation in Australia: barriers to translating new evidence into
      clinical practice.
AB  - Evidence "beyond reasonable doubt" may never be achievable for low-volume drugs.

PMID- 16646740
TI  - Preventing and processing research misconduct: a new Australian code for
      responsible research.

PMID- 16646741
TI  - Interface between residential aged care facilities and a teaching hospital
      emergency department in Western Australia.
AB  - OBJECTIVE: To estimate the appropriateness of emergency department (ED)
      presentations by people aged>or=65 years living in residential care facilities.
      DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of older residents
      of residential care facilities who presented to the ED of the Royal Perth
      Hospital, Western Australia, between January and June 2002. Data were reviewed by
      an expert clinical panel. MAIN OUTCOME MEASURES: Appropriateness of ED
      presentation, presenting complaint, involvement of a general practitioner/locum
      doctor prior to transfer, proportion of patients admitted to hospital from the
      ED, survival to discharge. RESULTS: 541 residents aged>or=65 years were
      transferred by ambulance to the ED, comprising 8.3% of all ED presentations of
      people in this age group. The mean age of the study cohort was 83.7 years (SD,
      7.0 years), of which 68% were women. Of the 541 presentations, 326 (60%) resulted
      in hospital admission, and of these, 276 (85%) survived to hospital discharge.
      Musculoskeletal disorders accounted for 25% of all presentations, and 22% were
      falls-related; pneumonia (11% of presentations) was the single largest presenting
      complaint. ED attendance was deemed "inappropriate" for 71/541 cases (13.1%; 95%
      CI, 10.5%-16.2%); in only 25% of ED presentations was a GP/locum doctor involved
      prior to transfer. CONCLUSIONS: The majority of ED presentations by aged care
      residents were considered to be appropriate, but there was scope for improvement
      in coordinating care between the hospital ED and residential care institutions.

PMID- 16646742
TI  - Learning opportunities for Australian prevocational hospital doctors: exposure,
      perceived quality and desired methods of learning.
AB  - OBJECTIVE: To survey prevocational doctors working in Australian hospitals on
      aspects of postgraduate learning. PARTICIPANTS AND SETTING: 470 prevocational
      doctors in 36 health services in Australia, August 2003 to October 2004. DESIGN:
      Cross-sectional cohort survey with a mix of ordinal multicategory questions and
      free text. MAIN OUTCOME MEASURES: Perceived preparedness for aspects of clinical
      practice; perceptions of the quantity and usefulness of current teaching and
      learning methods and desired future exposure to learning methods. RESULTS: 64%
      (299/467) of responding doctors felt generally prepared for their job, 91%
      (425/469) felt prepared for dealing with patients, and 70% (325/467) for dealing
      with relatives. A minority felt prepared for medicolegal problems (23%, 106/468),
      clinical emergencies (31%, 146/469), choosing a career (40%, 188/468), or
      performing procedures (45%, 213/469). Adequate contact with registrars was
      reported by 90% (418/465) and adequate contact with consultants by 56% (257/466);
      20% (94/467) reported exposure to clinical skills training and 11% (38/356) to
      high-fidelity simulation. Informal registrar contact was described as useful or
      very useful by 94% (433/463), and high-fidelity simulation by 83% (179/216). Most
      prevocational doctors would prefer more formal instruction from their registrars
      (84%, 383/456) and consultants (81%, 362/447); 84% (265/316) want increased
      exposure to high-fidelity simulation and 81% (283/350) to professional college
      tutorials. CONCLUSION: Our findings should assist planning and development of
      training programs for prevocational doctors in Australian hospitals.

PMID- 16646743
TI  - More doctors, but not enough: Australian medical workforce supply 2001-2012.
AB  - OBJECTIVE: To project the future size of the Australian medical workforce, from
      2001 to 2012. DESIGN AND SETTING: Stochastic simulation modelling of the
      Australian medical workforce, taking into account recent increases in medical
      school capacity and trends in the intake of foreign graduates. MAIN OUTCOME
      MEASURES: Number of full-time equivalent (FTE) medical practitioners per 100,000
      persons within various occupation groups from 2001 (baseline) to 2012. RESULTS:
      The total medical workforce was projected to rise from 53,384 in 2001 to 67,659
      by 2012 (95% CI, 63,924-71,036). On a per capita basis, the number of FTE
      clinicians was projected to rise from 331 per 100,000 persons in 2001 to 382 (95%
      CI, 359-403) per 100,000 persons in 2012. The general practice workforce was
      projected to fall from 133 FTE general practitioners per 100,000 persons in 2001,
      to 129 per 100,000 persons in 2003, and then remain at around this level through
      to 2012. The specialist workforce was projected to show steady growth, rising
      from 162 FTE specialists per 100,000 persons in 2001 to 206 (95% CI, 194-218) per
      100,000 persons in 2012. CONCLUSIONS: The general practice workforce is likely to
      face continued chronic shortages, necessitating innovative policy responses to
      ensure that the community's need for primary medical care is met. Retirement
      rates are a key determinant of workforce supply, suggesting a need to encourage
      general practitioners to remain active as long as they remain effective. Further
      refinement of stochastic models will help facilitate a more proactive approach to
      workforce planning.

PMID- 16646744
TI  - Sideswipe injuries to the elbow in Western Australia.
AB  - OBJECTIVE: To examine the conditions leading to sideswipe injury of the upper
      limb in motor vehicle accidents and to highlight the severity of these injuries.
      DESIGN AND SETTING: Prospective study of upper-limb sideswipe injuries in
      patients admitted to Royal Perth Hospital, Western Australia, between August 2003
      and January 2005. PARTICIPANTS: Eleven patients sustaining sideswipe injuries to
      the upper limb. MAIN OUTCOME MEASURES: Accident pattern, type of injury, surgical
      management, complications, and functional and employment implications. RESULTS:
      Ten patients required open reduction and internal fixation for open fractures of
      the humerus, ulna and radius, and nine underwent additional surgical procedures
      including nerve, artery and tendon repair, and free flaps and split-skin
      grafting. The injury severity scores ranged from 9 to 25. The severity of
      injuries led to extensive functional deficits in eight patients, affecting
      employment prospects in seven. CONCLUSION: Appropriate educational programs,
      legislation and improvements in traffic conditions, especially in rural areas, as
      well as changes in current car design, could contribute to preventing these
      devastating and complex injuries.

PMID- 16646745
TI  - Exasperations" of asthma: a qualitative study of patient language about worsening
      asthma.
AB  - OBJECTIVES: To identify expressions used by patients to describe worsening
      asthma; to examine the relevance of the word "exacerbation" to patients'
      experience; and to investigate whether their language is influenced by the
      severity of the episode and/or the target audience such as family members,
      friends and work colleagues. DESIGN AND SETTING: Qualitative study carried out
      from 1 January to 30 December 2004 among community volunteers to a research
      institute. Semistructured face-to-face interviews were used to elicit
      descriptions of episodes of worsening asthma, and further questioning was used to
      examine language used with family, employer and doctor. PARTICIPANTS: 25 people
      with asthma, aged 22-75 years. MAIN OUTCOME MEASURE: Themes identified by open
      coding about patient language for worsening asthma. RESULTS: 12 participants were
      not familiar with "exacerbation" and only three would use it themselves. "Attack"
      was the only specific term spontaneously volunteered (20 participants), but it
      was used for anything from mild to life-threatening episodes. Patients often
      downplayed the severity of worsening asthma to their families. Different language
      was used with employers, sometimes to justify sick leave and sometimes because of
      fear of perceived discrimination. When communicating with clinicians about
      worsening asthma, patients used symptom descriptors rather than specific terms.
      CONCLUSION: There are important differences in the language patients and
      clinicians use to describe worsening asthma, and the word "exacerbation" has poor
      utility for communication with patients.

PMID- 16646746
TI  - Modifiable risk factors for age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in Australia and other Western countries. As there is no cure for AMD,
      and treatments to stop its progression have met with limited success, there is an
      interest in identifying modifiable risk factors to prevent or slow disease
      progression. To date, smoking is the only proven modifiable risk factor for AMD.
      Other factors under study include (i) cardiovascular risk factors such as
      hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors
      including fat and antioxidant intake, but so far these studies have produced
      conflicting results. Dietary fat in relation to AMD has recently attracted media
      attention. Despite very limited work supporting an association between vegetable
      fat and AMD, widespread publicity advocating margarine as a cause of AMD and
      encouraging use of butter instead has caused confusion and anxiety among
      sufferers of AMD and the general public, as well as concern among health
      professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark
      green or yellow vegetables exist in high concentrations in the macula and are
      hypothesised to play a protective role. Of nine controlled trials of
      supplementation with carotenoids and other antioxidants, three suggested that
      various combinations of antioxidants and carotenoids were protective. While a low
      fat diet rich in dark green and yellow vegetables is advocated in general, any
      specific recommendations regarding certain fats or antioxidant supplementation
      and AMD are not based on consistent findings at this stage.

PMID- 16646747
TI  - Diagnosing bipolar disorder: how can we do it better?
AB  - Accurate diagnosis of bipolar disorder is essential for effective treatment. The
      diagnosis of bipolar disorder is particularly complex, resulting in lengthy
      delays between first presentation and initiation of appropriate therapy.
      Inappropriate therapy destabilises the course and outcome of the disease.
      Although the defining features of bipolar disorder are manic or hypomanic
      episodes, patients typically present for treatment of depression and commonly
      deny symptoms of mood elevation. A correct diagnosis can easily be masked by
      comorbidities, personality issues and complex phenomenology. A diagnosis of
      bipolar disorder can be assisted by: asking about symptoms of mania or hypomania
      in every patient presenting with symptoms of depression. recognising mixed states
      in which manic and depressive symptoms occur simultaneously. identifying the
      features of bipolar depression that distinguish it from unipolar depression.
      There is a risk of over-diagnosis of bipolar disorder among patients who are
      histrionic, show abnormal illness behaviour and/or have issues of secondary gain.

PMID- 16646748
TI  - The Research Quality Framework and its implications for health and medical
      research: time to take stock?
AB  - As the Australian university sector awaits final decisions about the introduction
      and stipulations of a research quality framework (RQF), to assess the quality and
      impact of research, we have studied international commentary on the value of such
      exercises. This suggests there is little hard evidence to recommend the proposed
      RQF. The UK government led the field in 1986 with its research assessment
      exercise (RAE), which is widely believed to have compromised clinical academic
      medicine by failing to satisfactorily acknowledge the contribution of clinical
      academics, not only to research but also to teaching and clinical practice. After
      the 2008 RAE, the UK government will move to a simpler, metrics-based system for
      assessing research quality and allocating funding. The New Zealand Performance
      Based Review Fund (PBRF), introduced in 2003, is based on a combination of peer
      review and performance indicators. Several concerns have been raised; among them
      is the real cost-benefit ratio of participation, with reports that many
      universities have spent more on the exercise than they will gain in funding
      increases. The scoring system has received the most criticism and, after the
      partial round assessment scheduled for this year, the controversial unit of
      assessment will be reviewed. It might be more cost-effective for Australia to
      modify existing research assessment processes than to undertake a potentially
      costly and arduous exercise.

PMID- 16646749
TI  - Abdominal pain and eosinophilia in suburban goat keepers--trichostrongylosis
      [corrected].

PMID- 16646750
TI  - Leprosy: an uncommon infection with varied presentations.

PMID- 16646751
TI  - The switch to new conjugated vaccines may compromise immunisation coverage for
      refugees.

PMID- 16646752
TI  - Vigilance is required for Australia to remain polio free.

PMID- 16646753
TI  - Murine typhus mimicking acute cholecystitis in a traveller.

PMID- 16646754
TI  - Chronic kidney disease and automatic reporting of estimated glomerular filtration
      rate.

PMID- 16646755
TI  - Is it time to review the screening guidelines for younger diabetic children?

PMID- 16646756
TI  - Medical handover.

PMID- 16646757
TI  - Screening couples for cystic fibrosis carrier status: why are we waiting?

PMID- 16646758
TI  - Impact of multiple impairments on quality of life, hospitalisations and use of
      aged-care services.

PMID- 16646759
TI  - Australia's media reporting of health and medical matters: a question of quality.

PMID- 16646760
TI  - It's time for action: do something to help.

PMID- 16646761
TI  - "Safe times: 11.30am-12.00 and 4.30pm-5.00".

PMID- 16646762
TI  - Routine outcome measurement in public mental health--what do clinicians think?

PMID- 16646763
TI  - Better outcomes in mental health care--a general practice perspective.

PMID- 16646764
TI  - Stakeholder concerns about Australia's mental health care system.
AB  - There is growing community and professional concern that the Australian mental
      health care system requires substantial reform. In response to these concerns, a
      Senate Select Committee on Mental Health has been commissioned to conduct an
      inquiry into the provision of mental health services. The current study involved
      a content analysis of 725 submissions received by the Committee, and highlighted
      significant areas for reform. People with mental illness face difficulties in
      accessing mental health care, the care they do receive is of varying quality and
      poorly coordinated, and necessary services from other sectors, such as housing,
      are lacking. These problems may be exacerbated for particular groups with complex
      needs or heightened levels of vulnerability. The system requires reorienting
      towards the consumers and carers it is designed to serve, and needs stronger
      governance, higher levels of accountability and improved monitoring of quality.
      These findings are discussed in the context of the recent acknowledgement of
      mental health as an issue by the Council of Australian Governments (COAG), which
      has called for an action plan to be prepared for its consideration by June 2006.

PMID- 16646765
TI  - Routine outcome measurement in public mental health: results of a clinician
      survey.
AB  - This paper explores the attitudes of mental health workers in one public mental
      health service towards the implementation and use of routine outcome measurement.
      Two years after their introduction into routine clinical practice, there were
      equal numbers of positive and negative observations from clinicians about the
      clinical value of the clinician-rated outcome measures, while more positive
      observations were made about value of the consumer-rated outcome measure. The
      most frequent observation from clinicians in relation to making outcome measures
      more useful to them in clinical practice was that more training, particularly
      refresher training, is needed. In addition, clinicians indicated that more
      sophisticated support which assists them to understand the meaning and possible
      use of outcome measure ratings is required.

PMID- 16646766
TI  - Balancing the balanced scorecard for a New Zealand mental health service.
AB  - Given the high prevalence of mental disorders, there is a need to evaluate mental
      health services to ensure they are efficient, effective, responsive and
      accessible. One method that is being used is the "balanced scorecard" which uses
      performance indicators in four quadrants to assess various dimensions of service
      provision. This case study describes the steps taken by a New Zealand mental
      health service to improve service management through greater use of key
      performance indicators in relation to preset targets using this approach.

PMID- 16646767
TI  - Reviewing the learning organisation model in a child and adolescent mental health
      service.
AB  - From 1995 onwards, a child and adolescent mental health service (CAMHS) applied
      Senge's learning organisation model. This review compared service performance
      with that of peer services 5 years later and explored whether any differences
      were associated with the application of this model. The comparison methodology
      used quantitative analysis of external data from the Department of Human
      Services, together with qualitative analysis of material including interviews
      with CAMHS directors and service managers. Results showed high evaluation
      activity and high quality, efficiency and efficacy of care compared with other
      services. Several restraints to the optimal application of the model were
      identified, including inadequate training of new managers, service overload,
      major external organisational change and limited investment in information
      systems. Other outcomes are discussed.

PMID- 16646768
TI  - Better access to psychology services in primary mental health care: an
      evaluation.
AB  - INTRODUCTION: The Access to Allied Psychological Services program was introduced
      as part of the Better Outcomes in Mental Health Care initiative in 2001-2002.
      Divisions of General Practice are funded to establish programs that allow GPs to
      refer patients for psychological treatments. The University of New South Wales
      evaluated programs run by the Southern Highlands and Illawarra Divisions of
      General Practice. This paper presents the findings of these evaluations. METHOD:
      Both evaluations analysed process and patient outcomes. This was obtained from a
      combination of program data and qualitative satisfaction data. RESULTS: The two
      program models differed in the mechanism of retention of the psychologists and
      the method of referral of patients. Anxiety and depression were the main reasons
      for referral, and clinical data showed there was improvement in patient outcomes.
      Patients, GPs and psychologists expressed satisfaction with the programs.
      DISCUSSION: The Access to Allied Psychological Services programs in both
      Divisions have proven popular. Flexibility in the program structure allows
      Divisions to develop a model which suits their local circumstances. There is
      support for ongoing Commonwealth funding and the challenge is to find the most
      effective and financially sustainable model of delivery for psychological
      services in primary care.

PMID- 16646769
TI  - Reducing aggressive behaviour and staff injuries: a multi-strategy approach.
AB  - OBJECTIVE: To evaluate the impact of a multi-strategy approach on the management
      of patient aggression and staff injury rates at a stand-alone mental health
      facility. METHODS: A multi-strategy aggression management program was developed
      and introduced over a 2-year period. The program had four components; staff
      education/training, a staff support program, risk assessment tools, and a
      computerised incident monitoring system. Aggressive incidents by patients, staff
      injuries due to patient aggression and compensation payments to staff for the 2
      year period before implementation of the aggression management program were
      compared with the 3-year period following implementation of the program. RESULTS:
      There was a significant decrease in the number of staff injuries reported in the
      3-year period following the implementation of the aggression management program.
      Although the number of aggressive incidents reported did decrease over the study
      period, the decrease was not statistically significant. CONCLUSIONS: Despite the
      increasing acuity of the clients at the study facility, there was a significant
      decrease in staff injuries due to aggressive behaviour. The strategies
      implemented seem to offset the potential for violence. It is likely that the
      combined impact of the strategies is greater than the impact of individual
      strategies implemented consecutively.

PMID- 16646770
TI  - Exploring the need for hepatology nurses and allied health professionals in
      Victorian liver clinics.
AB  - OBJECTIVE: To examine the need for hepatology nurses and allied health
      professionals in Victorian liver clinics to meet the increasing demand from
      people seeking treatment for hepatitis C infection. DESIGN: We reviewed the
      literature, analysed data from nine Victorian liver clinics, and conducted a
      qualitative rapid assessment with key stakeholders including hepatology nurses.
      PARTICIPANTS: Fourteen key stakeholders including clinicians and directors of
      liver clinics were invited to take part in interviews; two declined to
      participate. All ten members of the Victorian Hepatology Nurses Group were
      invited to participate in a focus group discussion, and six attended. RESULTS:
      Participants reported that hepatology nurses played a critical role in improving
      treatment uptake and compliance, in particular, in educating, counselling and
      managing treatment for people with hepatitis C infection. Psychiatric and social
      work staff assisted patients to overcome side effects associated with treatment.
      Interpreters increased access for those from culturally and linguistically
      diverse communities. CONCLUSIONS: Hepatology nurses and allied health
      professionals are central to enhancing treatment outcomes for people who are
      infected with hepatitis C. Further research is necessary to estimate the number
      of nurses and allied health professionals required to meet the current and future
      needs of people receiving treatment for hepatitis C infection.

PMID- 16646771
TI  - Scheduling unplanned surgery: a tool for improving dialogue about queue position
      on emergency theatre lists.
AB  - Theatre use is heavily influenced by the presentation and scheduling of emergency
      cases for unplanned surgery. This research guided the development of a triage
      standard for scheduling emergency surgery in New South Wales public hospitals and
      aimed to contribute to a better understanding of decision-making practices. An
      emergency-surgery survey asked questions about urgency of a set of clinical
      conditions and appropriate time frames for patients to receive surgical treatment
      for these conditions. Surveys were distributed via 71 NSW public hospitals. A
      total of 198 decision makers responded: surgeons (42.8%), anaesthetists (24.7%),
      and nurses (32.5%). Principal component analysis was applied to reduce the data
      to three urgency classifications, and analysis of variance was used to assess
      variance of opinions between professional groups. The data suggested that the
      parameters that distinguish the codes (1, very urgent; 2, semi-urgent; 3, least
      urgent) were not unequivocally apparent. Although there was a consistent approach
      to the "urgency 1" and "urgency 3" categories, there were significant differences
      between responses when determining "urgency 2". The data indicated that when
      making decisions, anaesthetists act as intermediaries between surgeons and
      nurses. There was significant disparity between individuals when respondents were
      asked to state an ideal time for the commencement of surgery and the maximum
      length of time that the surgery could wait. This presented a need for a risk
      assessment tool to be incorporated when developing a dynamic prototype triage
      instrument.

PMID- 16646772
TI  - The journey of a teaching hospital to become a learning organisation.
AB  - This paper describes how an acute tertiary referral hospital moved away from a
      "culture of blame", using change management principles aligned with the concept
      of the learning organisation. I outline the process of change, and describe its
      outcomes. The result is summarised as an improvement in desired attributes of the
      organisation's culture, as evidenced by consistent improvement in the results of
      a proprietary staff survey. I conclude that the concept of the learning
      organisation is a useful one for hospitals that seek to improve the
      organisational culture.

PMID- 16646773
TI  - The influence of federal health care policy reforms on the use of private health
      insurance in disadvantaged groups.
AB  - OBJECTIVE: To examine changes in the incidence rate ratio of private health
      insurance (PHI) and Medicare use for episodes of hospitalisation as a function of
      socio-economic status and accessibility to evaluate the impact of federal health
      policy reforms. METHODS: The WA Data Linkage System was used to extract all
      hospital morbidity records in Western Australia from 1991, 1996 and 2001.
      Adjusted odds ratios of PHI use were estimated in each socio-economic and
      locational accessibility category in each year using logistic regression. The
      odds ratios were then converted to adjusted incidence rate ratios controlled for
      population size. RESULTS: In all cases between 1991 and 1996 the adjusted
      incident rate ratios fell; this was followed by an increase in the adjusted rate
      ratio in 2001 to levels near those of 1991 in the most accessible--highest socio
      economically advantaged group. However in all other groups the increase fell
      short of the 1991 levels. The magnitude of the shortfall was associated with
      worsening accessibility or socio-economic status. In addition, significant
      changes in the within-group differential incident rate ratios were also observed
      over time. CONCLUSION: Our study indicates that the recent federal government
      policies which were aimed at making PHI more affordable to, and therefore more
      widely used by, lower to middle income earners were successful, lending empirical
      support for price elasticity of demand for PHI. Our results also indicate that
      the magnitude of their success varied according to disadvantage, suggesting that
      this elasticity is variable across both the level and typology of disadvantage.

PMID- 16646774
TI  - Private hospital insurance status among a state-wide injured population.
AB  - Injury is a leading cause of inpatient hospital episodes. Over a 4-year period
      (1997-2000) the Australian Government introduced measures to support the private
      health insurance industry by providing incentives for people to take up private
      health insurance (PHI) in order to take the pressure off public hospitals. This
      study examined the levels of PHI for moderately and severely injured people in
      Victoria as a way of determining the effectiveness of government incentives. The
      method involved an analysis of all Victorian public and private hospital injury
      admissions between July 2000 and June 2003. We found that people with injuries,
      either unintentional or intentional, had lower levels of PHI than state norms.
      While numbers of injured patients occupying private hospital beds initially
      increased, levels then dropped below the levels before the introduction of the
      incentives. The burden of injury is substantial and suggests that incentives need
      to be targeted towards at-risk groups.

PMID- 16646777
TI  - Pre-validation and inference in microarrays.
AB  - In microarray studies, an important problem is to compare a predictor of disease
      outcome derived from gene expression levels to standard clinical predictors.
      Comparing them on the same dataset that was used to derive the microarray
      predictor can lead to results strongly biased in favor of the microarray
      predictor. We propose a new technique called "pre-validation'' for making a
      fairer comparison between the two sets of predictors. We study the method
      analytically and explore its application in a recent study on breast cancer.

PMID- 16646778
TI  - An additive genetic gamma frailty model for two-locus linkage analysis using
      sibship age of onset data.
AB  - Complex human diseases are often due to multiple disease genes with variable age
      of onset, as well as both genetic and environmental risk factors. In order to
      simultaneously consider two possible disease loci and to incorporate age of onset
      and covariate information into genetic linkage analysis, we introduce a two-locus
      genetic gamma frailty model for age of onset data within a family. We show that
      this model can be used for genetic linkage analysis of diseases due to two
      possible disease loci. This model simultaneously considers allele-sharing at two
      different loci, and can easily incorporate age of onset or age at censoring data,
      environmental covariates data, and population disease rate data in genetic
      linkage analysis. It also provides a flexible framework for mapping loci
      affecting the risk of developing diseases with complex etiology. This approach
      allows multipoint allele-sharing analysis to take evidence of the existence of a
      disease locus in one region into account in mapping other disease loci.
      Simulation studies indicate that the proposed tests have expected type 1 error
      rates and when the model assumptions are met, increased power over one-locus
      model for linkage analysis. A prostate cancer data set is used for illustrating
      the methods.

PMID- 16646779
TI  - Use of mixture models in a microarray-based screening procedure for detecting
      differentially represented yeast mutants.
AB  - We describe the use of a statistical model in a genome-wide microarray-based
      yeast genetic screen performed by imposing different genetic selections on
      thousands of yeast mutants in parallel. A mixture model is fitted to data
      obtained from oligonucleotide arrays hybridized to 20-mer oligonucleotide
      "barcodes'' and a procedure based on the fitted model is used to search for
      mutants differentially represented under experimental and control conditions. The
      fitted stochastic model provides a way to assess uncertainty. We demonstrate the
      usefulness of the model by applying it to the problem of screening for components
      of the nonhomologous end joining (NHEJ) pathway and identified known components
      of the NHEJ pathway.

PMID- 16646780
TI  - Sampling correction in pedigree analysis.
AB  - Usually, a pedigree is sampled and included in the sample that is analyzed after
      following a predefined non-random sampling design comprising several specific
      procedures. To obtain a pedigree analysis result free from the bias caused by the
      sampling procedures, a correction is applied to the pedigree likelihood. The
      sampling procedures usually considered are: the pedigree ascertainment,
      determining whether a population unit is to be sampled; the intrafamilial
      pedigree extension, determining what part of the pedigree is to be sampled; and
      selective censoring of the sampled pedigree, determining whether it should be
      included in the sample to be analyzed. The probability of pedigree ascertainment
      is determined by the total set of potential probands in the true pedigree from
      which the sampled pedigree is obtained and we indicate how the necessary
      information on this set can be collected. If insufficient information on this set
      is observed, it is impossible to correct the pedigree likelihood adequately. Here
      we show that, if only the structure of this set is known, then an ascertainment
      model-based pedigree likelihood can be obtained by conditioning on this
      structure. An ascertainment-model-free (AMF) pedigree likelihood can be correctly
      constructed by conditioning on all the data in this set, i.e. on both its
      structure and its phenotypic content. However, if this set has missing data, the
      AMF likelihood becomes undefined, which limits the utility of this AMF approach
      originally proposed by Ewens and Shute (1986). We also consider the sampling
      correction necessary when the pedigrees included in the sample analyzed have been
      subjected to censoring. The forms of likelihood correction developed here provide
      asymptotically unbiased estimators of the genetic model only if the formulated
      model is correct, which means that it must correctly allow for the most important
      features of the true inheritance of the trait studied. Otherwise, if no special
      case of the formulated general model is close to the true inheritance model, then
      the forms of likelihood correction proposed here result in biases, the magnitude
      and direction of which depend on both the true model and the general analysis
      model that should subsume it.

PMID- 16646781
TI  - Parameter estimation for the calibration and variance stabilization of microarray
      data.
AB  - We derive and validate an estimator for the parameters of a transformation for
      the joint calibration (normalization) and variance stabilization of microarray
      intensity data. With this, the variances of the transformed intensities become
      approximately independent of their expected values. The transformation is similar
      to the logarithm in the high intensity range, but has a smaller slope for
      intensities close to zero. Applications have shown better sensitivity and
      specificity for the detection of differentially expressed genes. In this paper,
      we describe the theoretical aspects of the method. We incorporate calibration and
      variance-mean dependence into a statistical model and use a robust variant of the
      maximum-likelihood method to estimate the transformation parameters. Using
      simulations, we investigate the size of the estimation error and its dependence
      on sample size and the presence of outliers. We find that the error decreases
      with the square root of the number of probes per array and that the estimation is
      robust against the presence of differentially expressed genes. Software is
      publicly available as an R package through the Bioconductor project
      (http://www.bioconductor.org).

PMID- 16646782
TI  - Transformations for cDNA microarray data.
AB  - Two channel microarray data often contain systematic variations that can be
      minimized by data transformation prior to further analysis. The most commonly
      observed effects are revealed by viewing scatter plots of the logarithm of the
      ratio by the average logarithmic intensity of the two color channels (RI plots).
      In this paper we present a general model for signal intensity data with multiple
      error sources. We demonstrate how these sources of error influence the shape of
      an RI plot. We then compare some currently available transformation strategies in
      terms of their mechanism and performance on both simulated and real microarray
      data. A linlog transformation is proposed to stabilize the variance of the log
      ratios. We also propose a regional smoothing method to remove variation in log
      ratios due to spatial heterogeneity on the microarray surface. The discussed
      transformations represent an important initial step in microarray data analysis
      for both ratio-based and ANOVA methods.

PMID- 16646783
TI  - Supervised detection of regulatory motifs in DNA sequences.
AB  - Identification of transcription factor binding sites (regulatory motifs) is a
      major interest in contemporary biology. We propose a new likelihood based method,
      COMODE, for identifying structural motifs in DNA sequences. Commonly used methods
      (e.g. MEME, Gibbs motif sampler) model binding sites as families of sequences
      described by a position weight matrix (PWM) and identify PWMs that maximize the
      likelihood of observed sequence data under a simple multinomial mixture model.
      This model assumes that the positions of the PWM correspond to independent
      multinomial distributions with four cell probabilities. We address supervising
      the search for DNA binding sites using the information derived from structural
      characteristics of protein-DNA interactions. We extend the simple multinomial
      mixture model to a constrained multinomial mixture model by incorporating
      constraints on the information content profiles or on specific parameters of the
      motif PWMs. The parameters of this extended model are estimated by maximum
      likelihood using a nonlinear constraint optimization method. Likelihood-based
      cross-validation is used to select model parameters such as motif width and
      constraint type. The performance of COMODE is compared with existing motif
      detection methods on simulated data that incorporate real motif examples from
      Saccharomyces cerevisiae. The proposed method is especially effective when the
      motif of interest appears as a weak signal in the data. Some of the transcription
      factor binding data of Lee et al. (2002) were also analyzed using COMODE and
      biologically verified sites were identified.

PMID- 16646784
TI  - Visualisation of gene expression data - the GE-biplot, the Chip-plot and the Gene
      plot.
AB  - Visualisation methods for exploring microarray data are particularly important
      for gaining insight into data from gene expression experiments, such as those
      concerned with the development of an understanding of gene function and
      interactions. Further, good visualisation techniques are useful for outlier
      detection in microarray data and for aiding biological interpretation of results,
      as well as for presentation of overall summaries of the data. The biplot is
      particularly useful for the display of microarray data as both the genes and the
      chips can be simultaneously plotted. In this paper we describe several ordination
      techniques suitable for exploring microarray data, and we call these the GE
      biplot, the Chip-plot and the Gene-plot. The general method is first evaluated on
      synthetic data simulated in accord with current biological interpretation of
      microarray data. Then it is applied to two well-known data sets, namely the colon
      data of Alon et al. (1999) and the leukaemia data of Golub et al. (1999). The
      usefulness of the approach for interpreting and comparing different analyses of
      the same data is demonstrated.

PMID- 16646785
TI  - On the power of profiles for transcription factor binding site detection.
AB  - Transcription factor binding site (TFBS) detection plays an important role in
      computational biology, with applications in gene finding and gene regulation. The
      sites are often modeled by gapless profiles, also known as position-weight
      matrices. Past research has focused on the significance of profile scores (the
      ability to avoid false positives), but this alone is not enough: The profile must
      also possess the power to detect the true positive signals. Several completed
      genomes are now available, and the search for TFBSs is moving to a large scale;
      so discriminating signal from noise becomes even more challenging. Since TFBS
      profiles are usually estimated from only a few experimentally confirmed
      instances, careful regularization is an important issue. We present a novel
      method that is well suited for this situation. We further develop measures that
      help in judging profile quality, based on both sensitivity and selectivity of a
      profile. It is shown that these quality measures can be efficiently computed, and
      we propose statistically well-founded methods to choose score thresholds. Our
      findings are applied to the TRANSFAC database of transcription factor binding
      sites. The results are disturbing: If we insist on a significance level of 5% in
      sequences of length 500, only 19% of the profiles detect a true signal instance
      with 95% success probability under varying background sequence compositions.

PMID- 16646786
TI  - An empirical bayesian method for differential expression studies using one
      channel microarray data.
AB  - Gene expression microarrays have become powerful tools in many areas of
      biological and biomedical research. These technologies allow researchers to
      measure the expression levels of thousands of genes in a tissue or cell sample
      simultaneously. One of the most common types of microarray experiments is simply
      an exploratory study to compare two samples (e.g. tumor and normal tissue) and
      look for a list of genes that might be differentially expressed between the two.
      Differential expression is typically measured by computing a t-statistic or
      similar statistic for each gene. The genes are then ranked according to the
      absolute value of the t-statistic, and the twenty or fifty best candidates might
      be studied in follow-up experiments. When sample sizes are small, the t-statistic
      can be problematic, because variances are estimated poorly and the "top 20" list
      is often dominated by the genes with the lowest variance estimates. Lonnstedt and
      Speed (2001) proposed an empirical Bayes method for avoiding this problem, and
      showed that their approach has lower false positive and false negative rates than
      t-statistic-based methods. However, their method was designed mainly for the two
      channel microarray, which produces paired data. It is not suitable for
      technologies such as one-channel arrays that produce unpaired data. We propose a
      simplification for Lonnstedt and Speed's method, and then extend it to unpaired
      data with two or more independent treatments. We demonstrate our method on both
      simulated and real data. When the number of replicates is small, gene rankings
      based on our statistic appear to be much more reliable than rankings based on the
      t-statistic.

PMID- 16646787
TI  - Using alpha wisely: improving power to detect multiple QTL.
AB  - The increase in the number of available markers for many experimental populations
      has led to QTL studies with ever increasing marker numbers and densities. The
      resulting conundrum is that as marker density increases, so does the multiple
      testing problem. It is important to re-examine the detection of multiple QTL in
      light of increasing marker density. We explore through simulation whether
      existing methods have achieved the maximum possible power for detecting multiple
      QTL and whether increasing the marker density is an effective strategy for
      locating multiple QTL. In addition to existing methods, such as the maximum, the
      CET, and the Benjamini-Hochberg and Benjamini-Yekutieli procedures, we propose
      and evaluate the complete set of order statistics with their corresponding
      empirical joint distribution. We examine these statistics in conjunction with a
      novel application of the alpha-spending approach, providing a less conservative
      solution to the problem of controlling the false discovery rate (FDR) in multiple
      tests. We conducted a simulation study to assess the relative power of these
      approaches as well as their ability to control FDR. We find that several of the
      new approaches have a reasonable FDR, and can substantially improve the
      experimenter's ability to detect multiple QTL compared to existing approaches in
      many cases; however, the Benjamini-Hochberg procedure remains a very reasonable
      choice. The methods are applied to a nine-trait Oat vernalization dataset.

PMID- 16646788
TI  - Evaluation of multiple models to distinguish closely related forms of disease
      using DNA microarray data: an application to multiple myeloma.
AB  - MOTIVATION: Standard laboratory classification of the plasma cell dyscrasia
      monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma
      cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part,
      biologically uninformative. Most, if not all, cancers are caused by inherited or
      acquired genetic mutations that manifest themselves in altered gene expression
      patterns in the clonally related cancer cells. Microarray technology allows for
      qualitative and quantitative measurements of the expression levels of thousands
      of genes simultaneously, and it has now been used both to classify cancers that
      are morphologically indistinguishable and to predict response to therapy. It is
      anticipated that this information can also be used to develop molecular
      diagnostic models and to provide insight into mechanisms of disease progression,
      e.g., transition from healthy to benign hyperplasia or conversion of a benign
      hyperplasia to overt malignancy. However, standard data analysis techniques are
      not trivial to employ on these large data sets. Methodology designed to handle
      large data sets (or modified to do so) is needed to access the vital information
      contained in the genetic samples, which in turn can be used to develop more
      robust and accurate methods of clinical diagnostics and prognostics. RESULTS:
      Here we report on the application of a panel of statistical and data mining
      methodologies to classify groups of samples based on expression of 12,000 genes
      derived from a high density oligonucleotide microarray analysis of highly
      purified plasma cells from newly diagnosed MM, MGUS, and normal healthy donors.
      The three groups of samples are each tested against each other. The methods are
      found to be similar in their ability to predict group membership; all do quite
      well at predicting MM vs. normal and MGUS vs. normal. However, no method appears
      to be able to distinguish explicitly the genetic mechanisms between MM and MGUS.
      We believe this might be due to the lack of genetic differences between these two
      conditions, and may not be due to the failure of the models. We report the
      prediction errors for each of the models and each of the methods. Additionally,
      we report ROC curves for the results on group prediction. AVAILABILITY: Logistic
      regression: standard software, available, for example in SAS. Decision trees and
      boosted trees: C5.0 from www.rulequest.com. SVM: SVM-light is publicly available
      from svmlight.joachims.org. Naive Bayes and ensemble of voters are publicly
      available from www.biostat.wisc.edu/~mwaddell/eov.html. Nearest Shrunken
      Centroids is publicly available from http://www-stat.stanford.edu/~tibs/PAM.

PMID- 16646789
TI  - Saturation and quantization reduction in microarray experiments using two scans
      at different sensitivities.
AB  - We present a mathematical model to extend the dynamic range of gene expression
      data measured by laser scanners. The strategy is based on the rather simple but
      novel idea of producing two images with different scanner sensitivities,
      obtaining two different sets of expression values: the first is a low-sensitivity
      measure to obtain high expression values which would be saturated in a high
      sensitivity measure; the second, by the converse strategy, obtains additional
      information about the low-expression levels. Two mathematical models based on
      linear and gamma curves are presented for relating the two measurements to each
      other and producing a coherent and extended range of values. The procedure
      minimizes the quantization relative error and avoids the collateral effects of
      saturation. Since most of the current scanner devices are able to adjust the
      saturation level, the strategy can be considered as a universal solution, and not
      dependent on the image processing software used for reading the DNA chip. Various
      tests have been performed, on both proprietary and public domain data sets,
      showing a reduction of the saturation and quantization effects, not achievable by
      other methods, with a more complete description of gene-expression data and with
      a reasonable computational complexity.

PMID- 16646790
TI  - Combining nearest neighbor classifiers versus cross-validation selection.
AB  - Various discriminant methods have been applied for classification of tumors based
      on gene expression profiles, among which the nearest neighbor (NN) method has
      been reported to perform relatively well. Usually cross-validation (CV) is used
      to select the neighbor size as well as the number of variables for the NN method.
      However, CV can perform poorly when there is considerable uncertainty in choosing
      the best candidate classifier. As an alternative to selecting a single "winner,''
      we propose a weighting method to combine the multiple NN rules. Four gene
      expression data sets are used to compare its performance with CV methods. The
      results show that when the CV selection is unstable, the combined classifier
      performs much better.

PMID- 16646791
TI  - Multiple testing. Part I. Single-step procedures for control of general type I
      error rates.
AB  - The present article proposes general single-step multiple testing procedures for
      controlling Type I error rates defined as arbitrary parameters of the
      distribution of the number of Type I errors, such as the generalized family-wise
      error rate. A key feature of our approach is the test statistics null
      distribution (rather than data generating null distribution) used to derive cut
      offs (i.e., rejection regions) for these test statistics and the resulting
      adjusted p-values. For general null hypotheses, corresponding to submodels for
      the data generating distribution, we identify an asymptotic domination condition
      for a null distribution under which single-step common-quantile and common-cut
      off procedures asymptotically control the Type I error rate, for arbitrary data
      generating distributions, without the need for conditions such as subset
      pivotality. Inspired by this general characterization of a null distribution, we
      then propose as an explicit null distribution the asymptotic distribution of the
      vector of null value shifted and scaled test statistics. In the special case of
      family-wise error rate (FWER) control, our method yields the single-step minP and
      maxT procedures, based on minima of unadjusted p-values and maxima of test
      statistics, respectively, with the important distinction in the choice of null
      distribution. Single-step procedures based on consistent estimators of the null
      distribution are shown to also provide asymptotic control of the Type I error
      rate. A general bootstrap algorithm is supplied to conveniently obtain consistent
      estimators of the null distribution. The special cases of t- and F-statistics are
      discussed in detail. The companion articles focus on step-down multiple testing
      procedures for control of the FWER (van der Laan et al., 2004b) and on
      augmentations of FWER-controlling methods to control error rates such as tail
      probabilities for the number of false positives and for the proportion of false
      positives among the rejected hypotheses (van der Laan et al., 2004a). The
      proposed bootstrap multiple testing procedures are evaluated by a simulation
      study and applied to genomic data in the fourth article of the series (Pollard et
      al., 2004).

PMID- 16646792
TI  - Multiple testing. Part II. Step-down procedures for control of the family-wise
      error rate.
AB  - The present article proposes two step-down multiple testing procedures for
      asymptotic control of the family-wise error rate (FWER): the first procedure is
      based on maxima of test statistics (step-down maxT), while the second relies on
      minima of unadjusted p-values (step-down minP). A key feature of our approach is
      the characterization and construction of a test statistics null distribution
      (rather than data generating null distribution) for deriving cut-offs for these
      test statistics (i.e., rejection regions) and the resulting adjusted p-values.
      For general null hypotheses, corresponding to submodels for the data generating
      distribution, we identify an asymptotic domination condition for a null
      distribution under which the step-down maxT and minP procedures asymptotically
      control the Type I error rate, for arbitrary data generating distributions,
      without the need for conditions such as subset pivotality. Inspired by this
      general characterization, we then propose as an explicit null distribution the
      asymptotic distribution of the vector of null value shifted and scaled test
      statistics. Step-down procedures based on consistent estimators of the null
      distribution are shown to also provide asymptotic control of the Type I error
      rate. A general bootstrap algorithm is supplied to conveniently obtain consistent
      estimators of the null distribution.

PMID- 16646793
TI  - Augmentation procedures for control of the generalized family-wise error rate and
      tail probabilities for the proportion of false positives.
AB  - This article shows that any single-step or stepwise multiple testing procedure
      (asymptotically) controlling the family-wise error rate (FWER) can be augmented
      into procedures that (asymptotically) control tail probabilities for the number
      of false positives and the proportion of false positives among the rejected
      hypotheses. Specifically, given any procedure that (asymptotically) controls the
      FWER at level alpha, we propose simple augmentation procedures that provide
      (asymptotic) level-alpha control of: (i) the generalized family-wise error rate,
      i.e., the tail probability, gFWER(k), that the number of Type I errors exceeds a
      user-supplied integer k, and (ii) the tail probability, TPPFP(q), that the
      proportion of Type I errors among the rejected hypotheses exceeds a user-supplied
      value 0<q<1. Existing approaches for control of the proportion of false positives
      typically rely on the assumption that the test statistics are independent, while
      our proposed augmentation procedures control the gFWER and TPPFP for general data
      generating distributions, with arbitrary dependence structures among variables.
      Applying the augmentation methods to step-down multiple testing procedures that
      control the FWER asymptotically exactly at level alpha (van der Laan et al.,
      2004), yields procedures that also provide exact asymptotic control of the gFWER
      and TPPFP at level alpha. The adjusted p-values for the gFWER and TPPFP
      controlling augmentation procedures are shown to be simple functions of the
      adjusted p-values for the original FWER-controlling procedure. Finally, two
      simple conservative procedures are proposed for controlling the false discovery
      rate.

PMID- 16646794
TI  - Calculating the statistical significance of changes in pathway activity from gene
      expression data.
AB  - We present a statistical approach to scoring changes in activity of metabolic
      pathways from gene expression data. The method identifies the biologically
      relevant pathways with corresponding statistical significance. Based on gene
      expression data alone, only local structures of genetic networks can be
      recovered. Instead of inferring such a network, we propose a hypothesis-based
      approach. We use given knowledge about biological networks to improve sensitivity
      and interpretability of findings from microarray experiments. Recently introduced
      methods test if members of predefined gene sets are enriched in a list of top
      ranked genes in a microarray study. We improve this approach by defining scores
      that depend on all members of the gene set and that also take pairwise co
      regulation of these genes into account. We calculate the significance of co
      regulation of gene sets with a nonparametric permutation test. On two data sets
      the method is validated and its biological relevance is discussed. It turns out
      that useful measures for co-regulation of genes in a pathway can be identified
      adaptively. We refine our method in two aspects specific to pathways. First, to
      overcome the ambiguity of enzyme-to-gene mappings for a fixed pathway, we
      introduce algorithms for selecting the best fitting gene for a specific enzyme in
      a specific condition. In selected cases, functional assignment of genes to
      pathways is feasible. Second, the sensitivity of detecting relevant pathways is
      improved by integrating information about pathway topology. The distance of two
      enzymes is measured by the number of reactions needed to connect them, and enzyme
      pairs with a smaller distance receive a higher weight in the score calculation.

PMID- 16646795
TI  - A family-based association test for repeatedly measured quantitative traits
      adjusting for unknown environmental and/or polygenic effects.
AB  - We propose a family-based association test, FBAT-PC, for studies with
      quantitative traits that are measured repeatedly. The traits may be influenced by
      partially or completely unknown factors that may vary for each measurement. Using
      generalized principal component analysis, FBAT-PC amplifies the genetic effects
      of each measurement by constructing an overall phenotype with maximal
      heritability. Analytically, and in the simulation studies, we compare FBAT-PC
      with standard methodology and assess both the heritability of the overall
      phenotype and the power of FBAT-PC. Compared to univariate analysis, FBAT-PC
      achieves power gains of up to 200%. Applications of FBAT-PC to an osteoporosis
      study and to an asthma study show the practical relevance of FBAT-PC. FBAT-PC has
      been implemented in the software package PBAT and is freely available at
      http://www.biostat.harvard.edu/~clange/default.htm.

PMID- 16646796
TI  - Deletion/substitution/addition algorithm in learning with applications in
      genomics.
AB  - van der Laan and Dudoit (2003) provide a road map for estimation and performance
      assessment where a parameter of interest is defined as the risk minimizer for a
      suitable loss function and candidate estimators are generated using a loss
      function. After briefly reviewing this approach, this article proposes a general
      deletion/substitution/addition algorithm for minimizing, over subsets of
      variables (e.g., basis functions), the empirical risk of subset-specific
      estimators of the parameter of interest. This algorithm provides us with a new
      class of loss-based cross-validated algorithms in prediction of univariate
      outcomes, which can be extended to handle multivariate outcomes, conditional
      density and hazard estimation, and censored outcomes such as survival. In the
      context of regression, using polynomial basis functions, we study the properties
      of the deletion/substitution/addition algorithm in simulations and apply the
      method to detect transcription factor binding sites in yeast gene expression
      experiments.

PMID- 16646797
TI  - Classifying gene expression profiles from pairwise mRNA comparisons.
AB  - We present a new approach to molecular classification based on mRNA comparisons.
      Our method, referred to as the top-scoring pair(s) (TSP) classifier, is motivated
      by current technical and practical limitations in using gene expression
      microarray data for class prediction, for example to detect disease, identify
      tumors or predict treatment response. Accurate statistical inference from such
      data is difficult due to the small number of observations, typically tens,
      relative to the large number of genes, typically thousands. Moreover,
      conventional methods from machine learning lead to decisions which are usually
      very difficult to interpret in simple or biologically meaningful terms. In
      contrast, the TSP classifier provides decision rules which i) involve very few
      genes and only relative expression values (e.g., comparing the mRNA counts within
      a single pair of genes); ii) are both accurate and transparent; and iii) provide
      specific hypotheses for follow-up studies. In particular, the TSP classifier
      achieves prediction rates with standard cancer data that are as high as those of
      previous studies which use considerably more genes and complex procedures.
      Finally, the TSP classifier is parameter-free, thus avoiding the type of over
      fitting and inflated estimates of performance that result when all aspects of
      learning a predictor are not properly cross-validated.

PMID- 16646798
TI  - Relating HIV-1 sequence variation to replication capacity via trees and forests.
AB  - The problem of relating genotype (as represented by amino acid sequence) to
      phenotypes is distinguished from standard regression problems by the nature of
      sequence data. Here we investigate an instance of such a problem where the
      phenotype of interest is HIV-1 replication capacity and contiguous segments of
      protease and reverse transcriptase sequence constitutes genotype. A variety of
      data analytic methods have been proposed in this context. Shortcomings of select
      techniques are contrasted with the advantages afforded by tree-structured
      methods. However, tree-structured methods, in turn, have been criticized on
      grounds of only enjoying modest predictive performance. A number of ensemble
      approaches (bagging, boosting, random forests) have recently emerged, devised to
      overcome this deficiency. We evaluate random forests as applied in this setting,
      and detail why prediction gains obtained in other situations are not realized.
      Other approaches including logic regression, support vector machines and neural
      networks are also applied. We interpret results in terms of HIV-1 reverse
      transcriptase structure and function.

PMID- 16646799
TI  - Hierarchical Bayesian neural network for gene expression temporal patterns.
AB  - There are several important issues to be addressed for gene expression temporal
      patterns' analysis: first, the correlation structure of multidimensional temporal
      data; second, the numerous sources of variations with existing high level noise;
      and last, gene expression mostly involves heterogeneous multiple dynamic
      patterns. We propose a Hierarchical Bayesian Neural Network model to account for
      the input correlations of time course gene array data. The variations in absolute
      gene expression levels and the noise can be estimated with the hierarchical
      Bayesian setting. The network parameters and the hyperparameters were
      simultaneously optimized with Monte Carlo Markov Chain simulation. Results show
      that the proposed model and algorithm can well capture the dynamic feature of
      gene expression temporal patterns despite the high noise levels, the highly
      correlated inputs, the overwhelming interactions, and other complex features
      typically present in microarray data. We test and demonstrate the proposed models
      with yeast cell cycle temporal data sets. The model performance of Hierarchical
      Bayesian Neural Network was compared to other popular machine learning methods
      such as Nearest Neighbor, Support Vector Machine, and Self Organized Map.

PMID- 16646800
TI  - BayesMendel: an R environment for Mendelian risk prediction.
AB  - Several important syndromes are caused by deleterious germline mutations of
      individual genes. In both clinical and research applications it is useful to
      evaluate the probability that an individual carries an inherited genetic variant
      of these genes, and to predict the risk of disease for that individual, using
      information on his/her family history. Mendelian risk prediction models
      accomplish these goals by integrating Mendelian principles and state-of-the-art
      statistical models to describe phenotype/genotype relationships. Here we
      introduce an R library called BayesMendel that allows implementation of Mendelian
      models in research and counseling settings. BayesMendel is implemented in an
      object-oriented structure in the language R and distributed freely as an open
      source library. In its first release, it includes two major cancer syndromes: the
      breast-ovarian cancer syndrome and the hereditary non-polyposis colorectal cancer
      syndrome, along with up-to-date estimates of penetrance and prevalence for the
      corresponding genes. Input genetic parameters can be easily modified by users.
      BayesMendel can also serve as a generic tool for genetic epidemiologists to
      flexibly implement their own Mendelian models for novel syndromes and local
      subpopulations, without reprogramming complex statistical analyses and prediction
      tools.

PMID- 16646801
TI  - A mixed model approach to identify yeast transcriptional regulatory motifs via
      microarray experiments.
AB  - A genome-wide location analysis method has been introduced as a means to
      simultaneously study protein-DNA binding interactions for a large number of genes
      on a microarray platform. Identification of interactions between transcription
      factors (TF) and genes provide insight into the mechanisms that regulate a
      variety of cellular responses. Drawing proper inferences from the experimental
      data is key to finding statistically significant TF-gene binding interactions. We
      describe how the analysis and interpretation of genome-wide location data can be
      fit into a traditional statistical modeling framework that considers the data
      across all arrays and formulizes appropriate hypothesis tests. The approach is
      illustrated with data from a yeast transcription factor binding experiment that
      illustrates how identified TF-gene interactions can enhance initial exploration
      of transcriptional regulatory networks. Examples of five kinds of transcriptional
      regulatory structure are also demonstrated. Some stark differences with
      previously published results are explored.

PMID- 16646802
TI  - Mammalian genomes ease location of human DNA functional segments but not their
      description.
AB  - Under the assumption that a significant motivation for sequencing the genomes of
      mammals is the resulting ability to help us locate and characterize functional
      DNA segments shared with humans, we have developed a statistical analysis to
      quantify the expected advantage. Examining uncertainty in terms of the width of a
      confidence interval, we show that uncertainty in the rate of nucleotide mutation
      can be shrunk by a factor of nearly four when nine mammals; human, chimpanzee,
      baboon, cat, dog, cow, pig, rat, mouse; are used instead of just two; human and
      mouse. Contrastingly, we show confidence interval shrinkage by a factor of only
      1.5 for measurements of the distribution of nucleotides at an aligned sequence
      site. These additional genomes should greatly help in identifying conserved DNA
      sites, but would be much less effective at precisely describing the expected
      pattern of nucleotides at those sites.

PMID- 16646803
TI  - On the dependence structure of sequence alignment scores calculated with multiple
      scoring matrices.
AB  - A common practice in protein sequence alignment is to try several scoring
      matrices until "something interesting'' is found. This leads to a multiple
      testing problem making p- and E-values hard to interpret. We focus on local
      alignment and propose to use logistic copula functions to model explicitly the
      dependence structure of scores obtained using different scoring matrices. By
      doing this, we obtain p-value correction factors when using more than one scoring
      matrix on the same sequences. Furthermore the parameter of the logistic copula
      can be interpreted as measure of dependence, providing insight concerning the
      relatedness of the scores from different matrices.

PMID- 16646804
TI  - Concerns about unreliable data from spotted cDNA microarrays due to cross
      hybridization and sequence errors.
AB  - We discuss our concerns regarding the reliability of data generated by spotted
      cDNA microarrays. Two types of error we highlight are cross-hybridization
      artifact due to sequence homologies and sequence errors in the cDNA used for
      spotting on microarrays. We feel that statisticians who analyze microarray data
      should be aware of these sources of unreliability intrinsic to cDNA microarray
      design and use.

PMID- 16646805
TI  - Increasing power for tests of genetic association in the presence of phenotype
      and/or genotype error by use of double-sampling.
AB  - Phenotype and/or genotype misclassification can: significantly increase type II
      error probabilities for genetic case/control association, causing decrease in
      statistical power; and produce inaccurate estimates of population frequency
      parameters. We present a method, the likelihood ratio test allowing for errors
      (LRTae) that incorporates double-sample information for phenotypes and/or
      genotypes on a sub-sample of cases/controls. Population frequency parameters and
      misclassification probabilities are determined using a double-sample procedure as
      implemented in the Expectation-Maximization (EM) method. We perform null
      simulations assuming a SNP marker or a 4-allele (multi-allele) marker locus. To
      compare our method with the standard method that makes no adjustment for errors
      (LRTstd), we perform power simulations using a 2/k factorial design with high and
      low settings of: case/control samples, phenotype/genotype costs, double-sampled
      phenotypes/genotypes costs, phenotype/genotype error, and proportions of double
      sampled individuals. All power simulations are performed fixing equal costs for
      the LRTstd and LRTae methods. We also consider case/control ApoE genotype data
      for an actual Alzheimer's study. The LRTae method maintains correct type I error
      proportions for all null simulations and all significance level thresholds (10%,
      5%, 1%). LRTae average estimates of population frequencies and misclassification
      probabilities are equal to the true values, with variances of 10e-7 to 10e-8. For
      power simulations, the median power difference LRTae-LRTstd at the 5%
      significance level is 0.06 for multi-allele data and 0.01 for SNP data. For the
      ApoE data example, the LRTae and LRTstd p-values are 5.8 x 10e-5 and 1.6 x 10e-3,
      respectively. The increase in significance is due to adjustment in the LRTae for
      misclassification of the most commonly reported risk allele. We have developed
      freely available software that performs our LRTae statistic.

PMID- 16646806
TI  - A method for evaluating the impact of individual haplotypes on disease incidence
      in molecular epidemiology studies.
AB  - Estimation of the association between haplotypes and disease from a case-control
      study is considered. Assuming a single "disease haplotype'' leads to the
      increased risk, attention focusses on the relative risks associated with a single
      copy, or two copies of the disease haplotype, relative to individuals with no
      copies. In this setting, case frequencies of the haplotype pairs are in Hardy
      Weinberg Equilibrium (HWE) only if the combined influence of the two copies of
      the disease haplotype on risk is multiplicative. Thus, imputation cannot rely on
      the assumption of HWE for cases. A method is presented for obtaining estimates of
      the relative risks, making use of the EM algorithm and the assumption of HWE only
      for controls. The method accounts for the additional variation in the estimates
      due to the imputation of expected frequencies of haplotype pairs from ambiguous
      genotypes. A simulation study shows that the resulting confidence intervals have
      nominal coverage, and that the methods based on the assumption of HWE for both
      cases and controls can lead to bias.

PMID- 16646807
TI  - Statistical methods for identifying conserved residues in multiple sequence
      alignment.
AB  - The assessment of residue conservation in a multiple sequence alignment is a
      central issue in bioinformatics. Conserved residues and regions are used to
      determine structural and functional motifs or evolutionary relationships between
      the sequences of a multiple sequence alignment. For this reason, residue
      conservation is a valuable measure for database and motif search or for
      estimating the quality of alignments. In this paper, we present statistical
      methods for identifying conserved residues in multiple sequence alignments. While
      most earlier studies examine the positional conservation of the alignment, we
      focus on the detection of individual conserved residues at a position. The major
      advantages of multiple comparison methods originate from their ability to select
      conserved residues simultaneously and to consider the variability of the residue
      estimates. Large-scale simulations were used for the comparative analysis of the
      methods. Practical performance was studied by comparing the structurally and
      functionally important residues of Src homology 2 (SH2) domains to the
      assignments of the conservation indices. The applicability of the indices was
      also compared in three additional protein families comprising different degrees
      of entropy and variability in alignment positions. The results indicate that
      statistical multiple comparison methods are sensitive and reliable in identifying
      conserved residues.

PMID- 16646808
TI  - MergeMaid: R tools for merging and cross-study validation of gene expression
      data.
AB  - Cross-study validation of gene expression investigations is critical in genomic
      analysis. We developed an R package and associated object definitions to merge
      and visualize multiple gene expression datasets. Our merging functions use
      arbitrary character IDs and generate objects that can efficiently support a
      variety of joint analyses. Visualization tools support exploration and cross
      study validation of the data, without requiring normalization across platforms.
      Tools include "integrative correlation'' plots that is, scatterplots of all
      pairwise correlations in one study against the corresponding pairwise
      correlations of another, both for individual genes and all genes combined. Gene
      specific plots can be used to identify genes whose changes are reliably measured
      across studies. Visualizations also include scatterplots of gene-specific
      statistics quantifying relationships between expression and phenotypes of
      interest, using linear, logistic and Cox regression.

PMID- 16646809
TI  - Linear models and empirical bayes methods for assessing differential expression
      in microarray experiments.
AB  - The problem of identifying differentially expressed genes in designed microarray
      experiments is considered. Lonnstedt and Speed (2002) derived an expression for
      the posterior odds of differential expression in a replicated two-color
      experiment using a simple hierarchical parametric model. The purpose of this
      paper is to develop the hierarchical model of Lonnstedt and Speed (2002) into a
      practical approach for general microarray experiments with arbitrary numbers of
      treatments and RNA samples. The model is reset in the context of general linear
      models with arbitrary coefficients and contrasts of interest. The approach
      applies equally well to both single channel and two color microarray experiments.
      Consistent, closed form estimators are derived for the hyperparameters in the
      model. The estimators proposed have robust behavior even for small numbers of
      arrays and allow for incomplete data arising from spot filtering or spot quality
      weights. The posterior odds statistic is reformulated in terms of a moderated t
      statistic in which posterior residual standard deviations are used in place of
      ordinary standard deviations. The empirical Bayes approach is equivalent to
      shrinkage of the estimated sample variances towards a pooled estimate, resulting
      in far more stable inference when the number of arrays is small. The use of
      moderated t-statistics has the advantage over the posterior odds that the number
      of hyperparameters which need to estimated is reduced; in particular, knowledge
      of the non-null prior for the fold changes are not required. The moderated t
      statistic is shown to follow a t-distribution with augmented degrees of freedom.
      The moderated t inferential approach extends to accommodate tests of composite
      null hypotheses through the use of moderated F-statistics. The performance of the
      methods is demonstrated in a simulation study. Results are presented for two
      publicly available data sets.

PMID- 16646810
TI  - Sparse inverse of covariance matrix of QTL effects with incomplete marker data.
AB  - Gametic models for fitting breeding values at QTL as random effects in outbred
      populations have become popular because they require few assumptions about the
      number and distribution of QTL alleles segregating. The covariance matrix of the
      gametic effects has an inverse that is sparse and can be constructed rapidly by a
      simple algorithm, provided that all individuals have marker data, but not
      otherwise. An equivalent model, in which the joint distribution of QTL breeding
      values and marker genotypes is considered, was shown to generate a covariance
      matrix with a sparse inverse that can be constructed rapidly with a simple
      algorithm. This result makes more feasible including QTL as random effects in
      analyses of large pedigrees for QTL detection and marker assisted selection. Such
      analyses often use algorithms that rely upon sparseness of the mixed model
      equations and require the inverse of the covariance matrix, but not the
      covariance matrix itself. With the proposed model, each individual has two random
      effects for each possible unordered marker genotype for that individual.
      Therefore, individuals with marker data have two random effects, just as with the
      gametic model. To keep the notation and the derivation simple, the method is
      derived under the assumptions of a single linked marker and that the pedigree
      does not contain loops. The algorithm could be applied, as an approximate method,
      to pedigrees that contain loops.

PMID- 16646811
TI  - Maximum likelihood for genome phylogeny on gene content.
AB  - With the rapid growth of entire genome data, reconstructing the phylogenetic
      relationship among different genomes has become a hot topic in comparative
      genomics. Maximum likelihood approach is one of the various approaches, and has
      been very successful. However, there is no reported study for any applications in
      the genome tree-making mainly due to the lack of an analytical form of a
      probability model and/or the complicated calculation burden. In this paper we
      studied the mathematical structure of the stochastic model of genome evolution,
      and then developed a simplified likelihood function for observing a specific
      phylogenetic pattern under four genome situation using gene content information.
      We use the maximum likelihood approach to identify phylogenetic trees. Simulation
      results indicate that the proposed method works well and can identify trees with
      a high correction rate. Real data application provides satisfied results. The
      approach developed in this paper can serve as the basis for reconstructing
      phylogenies of more than four genomes.

PMID- 16646812
TI  - Confidence levels for the comparison of microarray experiments.
AB  - A common experimental strategy utilizing microarrays is to develop a signature of
      genes responding to some treatment in a model system, and then ask whether the
      same genes respond in an analogous way in a more natural and uncontrolled
      environment. In statistical terms, the question posed is whether genes score
      similarly on some statistical test in two independent data sets. Approaches to
      this problem ignoring gene/gene correlations common to all microarray data sets
      are known to give overstated statistical confidence levels. Permutation
      approaches have been proposed to give more accurate confidence levels, but can
      not be applied when sample sizes are small. Here we argue that the product moment
      correlation between test statistics in the two experiments is an ideal measure
      for summarizing concordance between the experiments, as confidence levels
      accounting for intergene correlations depend only on a single number - the
      average squared correlation between gene pairs in the data set. The resulting
      null standard deviation is shown to vary by less than a factor of two over six
      distinct experimental data sets, suggesting that a universal constant may be used
      for this quantity. We show how a hidden assumption of the permutation approach
      may lead to incorrect p-values, while the analytic approach presented here is
      shown to be resistant to this assumption.

PMID- 16646813
TI  - PLS dimension reduction for classification with microarray data.
AB  - Partial Least Squares (PLS) dimension reduction is known to give good prediction
      accuracy in the context of classification with high-dimensional microarray data.
      In this paper, the classification procedure consisting of PLS dimension reduction
      and linear discriminant analysis on the new components is compared with some of
      the best state-of-the-art classification methods. Moreover, a boosting algorithm
      is applied to this classification method. In addition, a simple procedure to
      choose the number of PLS components is suggested. The connection between PLS
      dimension reduction and gene selection is examined and a property of the first
      PLS component for binary classification is proved. In addition, we show how PLS
      can be used for data visualization using real data. The whole study is based on 9
      real microarray cancer data sets.

PMID- 16646814
TI  - Statistical analysis of genomic tag data.
AB  - We present a series of statistical solutions to challenges that commonly arise in
      the production and analysis of genomic tag libraries. Tag libraries are
      collections of fragments of DNA or RNA, with each unique fragment often present
      in millions or billions of copies. Inferences can be made from data obtained by
      sequencing a subset of the library. The statistical approaches outlined in this
      paper are divided into three parts. First, we demonstrate the application of
      classical capture-recapture theory to the question of library complexity, i.e.
      the number of unique fragments in the library. Simulation studies verify the
      accuracy, for sample sizes of magnitudes typical in genomic studies, of the
      formulas we use to make our estimates. Second, we present a straightforward
      statistical cost analysis of tag experiments designed to uncover either disease
      causing pathogens or new genes. Third, we develop a hidden Markov model approach
      to karyotyping a sample using a tag library derived from the sample's genomic
      DNA. While the resolution of the approach depends upon the number of tags
      sequenced from the library, we show via simulation that copy number alterations
      can be reliably detected for lengths as small as 1 Mb, even when a moderate
      number of tags are sequenced. Simulations predict very good specificity as well.
      Finally, all three of our approaches are applied to data from real tag library
      experiments. The hidden Markov model results are in line with what was expected
      from simulation, and genomic alterations found by applying the method to a cancer
      cell line library are confirmed using PCR. The methods and data described in this
      paper are contained in an R package, tagAnalysis, freely available at
      http://meyerson.dfci.harvard.edu/~tl974/tagAnalysis.

PMID- 16646815
TI  - Statistical analysis of adsorption models for oligonucleotide microarrays.
AB  - Recent analyses have shown that the relationship between intensity measurements
      from high density oligonucleotide microarrays and known concentration is non
      linear. Thus many measurements of so-called gene expression are neither measures
      of transcript nor mRNA concentration as might be expected. Intensity as measured
      in such microarrays is a measurement of fluorescent dye attached to probe-target
      duplexes formed during hybridization of a sample to the probes on the microarray.
      We develop several dynamic adsorption models relating fluorescent dye intensity
      to target RNA concentration, the simplest of which is the equilibrium Langmuir
      isotherm, or hyperbolic response function. Using data from the Affymerix HG-U95A
      Latin Square experiment, we evaluate various physical models, including
      equilibrium and non-equilibrium models, by applying maximum likelihood methods.
      We show that for these data, equilibrium Langmuir isotherms with probe dependent
      parameters are appropriate. We describe how probe sequence information may then
      be used to estimate the parameters of the Langmuir isotherm in order to provide
      an improved measure of absolute target concentration.

PMID- 16646816
TI  - Statistical significance threshold criteria for analysis of microarray gene
      expression data.
AB  - The methodological advancement in microarray data analysis on the basis of false
      discovery rate (FDR) control, such as the q-value plots, allows the investigator
      to examine the FDR from several perspectives. However, when FDR control at the
      "customary" levels 0.01, 0.05, or 0.1 does not provide fruitful findings, there
      is little guidance for making the trade off between the significance threshold
      and the FDR level by sound statistical or biological considerations. Thus,
      meaningful statistical significance criteria that complement the existing FDR
      methods for large-scale multiple tests are desirable. Three statistical
      significance criteria, the profile information criterion, the total error
      proportion, and the guide-gene driven selection, are developed in this research.
      The first two are general significance threshold criteria for large-scale
      multiple tests; the profile information criterion is related to the recent
      theoretical studies of the connection between FDR control and minimax estimation,
      and the total error proportion is closely related to the asymptotic properties of
      FDR control in terms of the total error risk. The guide-gene driven selection is
      an approach to combining statistical significance and the existing biological
      knowledge of the study at hand. Error properties of these criteria are
      investigated theoretically and by simulation. The proposed methods are
      illustrated and compared using an example of genomic screening for novel Arf gene
      targets. Operating characteristics of q-value and the proposed significance
      threshold criteria are investigated and compared in a simulation study that
      employs a model mimicking a gene regulatory pathway. A guideline for using these
      criteria is provided. Splus/R code is available from the corresponding author
      upon request.

PMID- 16646817
TI  - A compendium to ensure computational reproducibility in high-dimensional
      classification tasks.
AB  - We demonstrate a concept and implementation of a compendium for the
      classification of high-dimensional data from microarray gene expression profiles.
      A compendium is an interactive document that bundles primary data, statistical
      processing methods, figures, and derived data together with the textual
      documentation and conclusions. Interactivity allows the reader to modify and
      extend these components. We address the following questions: how much does the
      discriminatory power of a classifier depend on the choice of the algorithm that
      was used to identify it; what alternative classifiers could be used just as well;
      how robust is the result. The answers to these questions are essential
      prerequisites for validation and biological interpretation of the classifiers. We
      show how to use this approach by looking at these questions for a specific breast
      cancer microarray data set that first has been studied by Huang et al. (2003).

PMID- 16646818
TI  - Validation and discovery in Markov models of genetics data.
AB  - Markov models provide a natural framework for modeling cellular and molecular
      level changes over time. Kalbfleisch and Lawless propose using a Chi-squared
      statistic for assessing the appropriateness of assuming a first-order,
      homogeneous Markov process. While this statistic provides a global test of the
      Markov assumption, it does not permit identification of individual departures. We
      consider two approaches for discovering specific departures from the Markov
      assumption. First, we propose a diagnostic that tests whether the number of
      observed transitions out of a given state at a given time point is different than
      expected. Second, we construct statistics based on the number of observations in
      each state at each time point. In both cases, we construct multiple correlated
      statistics and testing is achieved through simulations. These approaches are
      applied to HIV genetics sequences measured over time.

PMID- 16646819
TI  - Making sense of high-throughput protein-protein interaction data.
AB  - Accurate systems biology modeling requires a complete catalog of protein
      complexes and their constituent proteins. We discuss a graph
      theoretic/statistical algorithm for local dynamic modeling of protein complexes
      using data from affinity purification-mass spectrometry experiments. The
      algorithm readily accommodates multicomplex membership by individual proteins and
      dynamic complex composition, two biological realities not accounted for in
      existing topological descriptions of the overall protein network. A likelihood
      based objective function guides the protein complex modeling algorithm. With an
      accurate complex membership catalog in place, systems biology can proceed with
      greater precision.

PMID- 16646820
TI  - Asymptotic optimality of likelihood-based cross-validation.
AB  - Likelihood-based cross-validation is a statistical tool for selecting a density
      estimate based on n i.i.d. observations from the true density among a collection
      of candidate density estimators. General examples are the selection of a model
      indexing a maximum likelihood estimator, and the selection of a bandwidth
      indexing a nonparametric (e.g. kernel) density estimator. In this article, we
      establish a finite sample result for a general class of likelihood-based cross
      validation procedures (as indexed by the type of sample splitting used, e.g. V
      fold cross-validation). This result implies that the cross-validation selector
      performs asymptotically as well (w.r.t. to the Kullback-Leibler distance to the
      true density) as a benchmark model selector which is optimal for each given
      dataset and depends on the true density. Crucial conditions of our theorem are
      that the size of the validation sample converges to infinity, which excludes
      leave-one-out cross-validation, and that the candidate density estimates are
      bounded away from zero and infinity. We illustrate these asymptotic results and
      the practical performance of likelihood-based cross-validation for the purpose of
      bandwidth selection with a simulation study. Moreover, we use likelihood-based
      cross-validation in the context of regulatory motif detection in DNA sequences.

PMID- 16646821
TI  - Using importance sampling to improve simulation in linkage analysis.
AB  - In this article we describe and discuss implementation of a weighted simulation
      procedure, importance sampling, in the context of nonparametric linkage analysis.
      The objective is to estimate genome-wide p-values, i.e. the probability that the
      maximal linkage score exceeds given thresholds under the null hypothesis of no
      linkage. In order to reduce variance of the estimate for large thresholds, we
      simulate linkage scores under a distribution different from the null with an
      artificial disease locus positioned somewhere along the genome. To compensate for
      the fact that we simulate under the wrong distribution, the simulated scores are
      reweighted using a certain likelihood ratio. If the sampling distribution are
      properly chosen the variance of the corresponding estimate is reduced. This
      results in accurate genome-wide p-value estimates for a wide range of large
      thresholds with a substantially smaller cost adjusted relative efficiency with
      respect to standard unweighted simulation. We illustrate the performance of the
      method for several pedigree examples, discuss implementation including the amount
      of variance reduction and describe some possible generalizations.

PMID- 16646822
TI  - Model-based assignment and inference of protein backbone Nuclear Magnetic
      Resonances.
AB  - Nuclear Magnetic Resonance (NMR) spectroscopy is a key experimental technique
      used to study protein structure, dynamics, and interactions. NMR methods face the
      bottleneck of spectral analysis, in particular determining the resonance
      assignments, which help define the mapping between atoms in the protein and peaks
      in the spectra. A substantial amount of noise in spectral data, along with
      ambiguities in interpretation, make this analysis a daunting task, and there
      exists no generally accepted measure of uncertainty associated with the resulting
      solutions. This paper develops a model-based inference approach that addresses
      the problem of characterizing uncertainty in backbone resonance assignment. We
      argue that NMR spectra are subject to random variation, and ignoring this
      stochasticity can lead to false optimism and erroneous conclusions. We propose a
      Bayesian statistical model that accounts for various sources of uncertainty and
      provides an automatable framework for inference. While assignment has previously
      been viewed as a deterministic optimization problem, we demonstrate the
      importance of considering all solutions consistent with the data, and develop an
      algorithm to search this space within our statistical framework. Our approach is
      able to characterize the uncertainty associated with backbone resonance
      assignment in several ways: 1) it quantifies of uncertainty in the individually
      assigned resonances in terms of their posterior standard deviations; 2) it
      assesses the information content in the data with a posterior distribution of
      plausible assignments; and 3) it provides a measure of the overall plausibility
      of assignments. We demonstrate the value of our approach in a study of
      experimental data from two proteins, Human Ubiquitin and Cold-shock protein A
      from E. coli. In addition, we provide simulations showing the impact of
      experimental conditions on uncertainty in the assignments.

PMID- 16646824
TI  - Error-rate and decision-theoretic methods of multiple testing: which genes have
      high objective probabilities of differential expression?
AB  - Given a multiple testing situation, the null hypotheses that appear to have
      sufficiently low probabilities of truth may be rejected using a simple,
      nonparametric method based on decision theory. This applies not only to posterior
      levels of belief, but also to conditional probabilities in the sense of relative
      frequencies, as seen from their equality to local false discovery rates (dFDRs).
      This approach neither requires the estimation of probability densities, nor of
      their ratios. Decision theory can also inform the selection of false discovery
      rate weights. An application to gene expression microarrays is presented with a
      discussion of the applicability of the assumption of "clumpy dependence."

PMID- 16646826
TI  - Estimating motifs under order restrictions.
AB  - Transcription factors and many other DNA-binding proteins recognize more than one
      specific sequence. Among sequences recognized by a given DNA-binding protein,
      different positions exhibit varying degrees of conservation. The reason is that
      base pairs that are more extensively contacted by the protein tend to be more
      conserved. This observation can be used in the discovery of transcription factor
      binding sites. Here we present a rigorous means to accomplish this. In
      particular, we constrain the order of the information (entropy) in the columns of
      the position specific weight matrix (PWM) which characterizes the motif being
      sought. We then show how to compute the maximum likelihood estimate of a PWM
      under such order restrictions. This computation is easily integrated with the EM
      algorithm or the Gibbs sampler to enhance performance in the search for motifs in
      unaligned sequences. We demonstrate our method on a well-known data set of
      binding sites of the transcription factor Crp in E. coli.

PMID- 16646827
TI  - Prediction of missing values in microarray and use of mixed models to evaluate
      the predictors.
AB  - Gene expression microarray experiments generate data sets with multiple missing
      expression values. In some cases, analysis of gene expression requires a complete
      matrix as input. Either genes with missing values can be removed, or the missing
      values can be replaced using prediction. We propose six imputation methods. A
      comparative study of the methods was performed on data from mice and data from
      the bacterium Enterococcus faecalis, and a linear mixed model was used to test
      for differences between the methods. The study showed that different methods'
      capability to predict is dependent on the data, hence the ideal choice of method
      and number of components are different for each data set. For data with
      correlation structure methods based on K-nearest neighbours seemed to be best,
      while for data without correlation structure using the average of the gene was to
      be preferred.

PMID- 16646828
TI  - Combined association and linkage analysis for general pedigrees and genetic
      models.
AB  - A combined score test for association and linkage analysis is introduced, based
      on a biologically plausible model with association between markers and causal
      genes and penetrance between phenotypes and the causal gene. The test is based on
      a retrospective likelihood of marker data given phenotypes, treating the alleles
      of the causal gene as hidden data. It is defined for arbitrary outbred pedigrees,
      a wide class of genetic models including polygenic and shared environmental
      effects and allows for missing marker data. It is multipoint, taking marker
      genotypes from several loci into account simultaneously. The score vector has one
      association and one linkage component, which can be used to define separate tests
      for association and linkage. For complete marker data, we give closed form
      expressions for the efficiency of the linkage, association and combined tests.
      These are examplified for binary and quantitative phenotypes with or without
      polygenic effects. The conclusion is that association tests are comparatively
      more efficient than linkage tests for strong association, weak penetrance models,
      small families and non-extreme phenotypes, whereas the linkage test is more
      efficient for weak association, strong penetrance models, large families and
      extreme phenotypes. The combined test is a robust alternative, which never
      performs much worse than the best of the linkage and association tests, and
      sometimes significantly better than both of them. It should be particularly
      useful when little is known about the genetic model.

PMID- 16646829
TI  - Incorporating biological information as a prior in an empirical bayes approach to
      analyzing microarray data.
AB  - Currently the practice of using existing biological knowledge in analyzing high
      throughput genomic and proteomic data is mainly for the purpose of validations.
      Here we take a different approach of incorporating biological knowledge into
      statistical analysis to improve statistical power and efficiency. Specifically,
      we consider how to fuse biological information into a mixture model to analyze
      microarray data. In contrast to a standard mixture model where it is assumed that
      all the genes come from the same (marginal) distribution, including an equal
      prior probability of having an event, such as having differential expression or
      being bound by a transcription factor (TF), our proposed mixture model allows the
      genes in different groups to have different distributions while the grouping of
      the genes reflects biological information. Using a list of about 800 putative
      cell cycle-regulated genes as prior biological knowledge, we analyze a genome
      wide location data to detect binding sites of TF Fkh1. We find that our proposal
      improves over the standard approach, resulting in reduced false discovery rates
      (FDR), and hence it is a useful alternative to the current practice.

PMID- 16646830
TI  - The relative inefficiency of sequence weights approaches in determining a
      nucleotide position weight matrix.
AB  - Approaches based upon sequence weights, to construct a position weight matrix of
      nucleotides from aligned inputs, are popular but little effort has been expended
      to measure their quality. We derive optimal sequence weights that minimize the
      sum of the variances of the estimators of base frequency parameters for sequences
      related by a phylogenetic tree. Using these we find that approaches based upon
      sequence weights can perform very poorly in comparison to approaches based upon a
      theoretically optimal maximum-likelihood method in the inference of the
      parameters of a position-weight matrix. Specifically, we find that among a
      collection of primate sequences, even an optimal sequences-weights approach is
      only 51% as efficient as the maximum-likelihood approach in inferences of base
      frequency parameters. We also show how to employ the variance estimators to
      obtain a greedy ordering of species for sequencing. Application of this ordering
      for the weighted estimators to a primate collection yields a curve with a long
      plateau that is not observed with maximum-likelihood estimators. This plateau
      indicates that the use of weighted estimators on these data seriously limits the
      utility of obtaining the sequences of more than two or three additional species.

PMID- 16646831
TI  - A simple loglinear model for haplotype effects in a case-control study involving
      two unphased genotypes.
AB  - Because haplotypes may parsimoniously summarize the effect of genes on disease,
      there is great interest in using haplotypes in case-control studies of unphased
      genotype data. Previous methods for investigating haplotypes effects in case
      control studies have not allowed for both of the following two scenarios that
      could have a large impact on results (i) departures from Hardy-Weinberg
      equilibrium in controls as well as cases, and (ii) an interactive effect of
      haplotypes and environmental covariates on the probability of disease. A new
      method is proposed that generalizes the model of Epstein and Satten to
      incorporate both (i) and (ii). Computations are relatively simple involving a
      single loglinear design matrix for parameters modeling the distribution of
      haplotype frequencies in controls, parameters modeling the effect of haplotypes
      and covariate-haplotype interactions on disease, and nuisance parameters required
      for correct inference. Based on simulations with realistic sample sizes, the
      method is recommended with data from two genotypes, a recessive or dominant model
      linking haplotypes to disease, and estimates of haplotype effects among
      haplotypes with a frequency greater than 10%. The methodology is most useful with
      candidate genotype pairs or for searching through pairs of genotypes when
      scenarios (i) and (ii) are likely. An example without a covariate illustrates the
      importance of modeling a departure from Hardy-Weinberg equilibrium in controls.

PMID- 16646832
TI  - Extension of the SIMLA package for generating pedigrees with complex inheritance
      patterns: environmental covariates, gene-gene and gene-environment interaction.
AB  - We have previously distributed a software package, SIMLA (SIMulation of Linkage
      and Association), which can be used to generate disease phenotype and marker
      genotype data in three-generational pedigrees of user-specified structure. To our
      knowledge, SIMLA is the only publicly available program that can simulate
      variable levels of both linkage (recombination) and linkage disequilibrium (LD)
      between marker and disease loci in general pedigrees. While the previous SIMLA
      version provided flexibility in choosing many parameters relevant for linkage and
      association mapping of complex human diseases, it did not allow for the
      segregation of more than one disease locus in a given pedigree and did not
      incorporate environmental covariates possibly interacting with disease
      susceptibility genes. Here, we present an extension of the simulation algorithm
      characterized by a much more general penetrance function, which allows for the
      joint action of up to two genes and up to two environmental covariates in the
      simulated pedigrees, with all possible multiplicative interaction effects between
      them. This makes the program even more useful for comparing the performance of
      different linkage and association analysis methods applied to complex human
      phenotypes. SIMLA can assist investigators in planning and designing a variety of
      linkage and association studies, and can help interpret results of real data
      analyses by comparing them to results obtained under a user-controlled data
      generation mechanism.A free download of the SIMLA package is available at
      http://wwwchg.duhs.duke.edu/software.

PMID- 16646833
TI  - Error distribution for gene expression data.
AB  - We present a new instance of Laplace's second Law of Errors and show how it can
      be used in the analysis of data from microarray experiments. This error
      distribution is shown to fit microarray expression data much better than a normal
      distribution. The use of this distribution in a parametric bootstrap leads to
      more powerful tests as we show that the t-test is conservative in this setting.
      We propose a biological explanations for this distribution based on the Pareto
      distribution of the variables used to compute the log ratios.

PMID- 16646834
TI  - A general framework for weighted gene co-expression network analysis.
AB  - Gene co-expression networks are increasingly used to explore the system-level
      functionality of genes. The network construction is conceptually straightforward:
      nodes represent genes and nodes are connected if the corresponding genes are
      significantly co-expressed across appropriately chosen tissue samples. In
      reality, it is tricky to define the connections between the nodes in such
      networks. An important question is whether it is biologically meaningful to
      encode gene co-expression using binary information (connected=1, unconnected=0).
      We describe a general framework for ;soft' thresholding that assigns a connection
      weight to each gene pair. This leads us to define the notion of a weighted gene
      co-expression network. For soft thresholding we propose several adjacency
      functions that convert the co-expression measure to a connection weight. For
      determining the parameters of the adjacency function, we propose a biologically
      motivated criterion (referred to as the scale-free topology criterion). We
      generalize the following important network concepts to the case of weighted
      networks. First, we introduce several node connectivity measures and provide
      empirical evidence that they can be important for predicting the biological
      significance of a gene. Second, we provide theoretical and empirical evidence
      that the ;weighted' topological overlap measure (used to define gene modules)
      leads to more cohesive modules than its ;unweighted' counterpart. Third, we
      generalize the clustering coefficient to weighted networks. Unlike the unweighted
      clustering coefficient, the weighted clustering coefficient is not inversely
      related to the connectivity. We provide a model that shows how an inverse
      relationship between clustering coefficient and connectivity arises from hard
      thresholding. We apply our methods to simulated data, a cancer microarray data
      set, and a yeast microarray data set.

PMID- 16646835
TI  - Statistical inference in evolutionary models of DNA sequences via the EM
      algorithm.
AB  - We describe statistical inference in continuous time Markov processes of DNA
      sequences related by a phylogenetic tree. The maximum likelihood estimator can be
      found by the expectation maximization (EM) algorithm and an expression for the
      information matrix is also derived. We provide explicit analytical solutions for
      the EM algorithm and information matrix.

PMID- 16646836
TI  - Comparing bacterial DNA microarray fingerprints.
AB  - Epidemiologic and forensic investigations often require assays to detect subtle
      genetic differences between closely related microorganisms. Typically, gel
      electrophoresis is used to compare randomly amplified DNA fragments between
      microbial samples, where the patterns of DNA fragment sizes are viewed as
      genotype 'fingerprints'. The limited genomic sample captured on a gel, however,
      is not always sufficient to discriminate closely related strains. This paper
      examines the application of microarray technology to DNA fingerprinting as a high
      resolution alternative to gel-based methods. The so-called universal microarray,
      which uses short oligonucleotide probes that do not target specific genes or
      species, is intended to be applicable to all microorganisms because it does not
      require prior knowledge of genomic sequence. In principle, closely related
      strains can be distinguished if enough independent oligonucleotide probes are
      used on the microarray, i.e., if the genome is sufficiently sampled. In practice,
      we confront noisy data, imperfectly matched hybridizations, and a high
      dimensional inference problem. We describe the statistical problems of microarray
      fingerprinting, outline similarities with and differences from more conventional
      microarray applications, and illustrate a statistical measurement error model to
      fingerprint 10 closely related strains from three Bacillus species, and 3 strains
      from non-Bacillus species.

PMID- 16646837
TI  - Reproducible research: a bioinformatics case study.
AB  - While scientific research and the methodologies involved have gone through
      substantial technological evolution the technology involved in the publication of
      the results of these endeavors has remained relatively stagnant. Publication is
      largely done in the same manner today as it was fifty years ago. Many journals
      have adopted electronic formats, however, their orientation and style is little
      different from a printed document. The documents tend to be static and take
      little advantage of computational resources that might be available. Recent work,
      Gentleman and Temple Lang (2003), suggests a methodology and basic infrastructure
      that can be used to publish documents in a substantially different way. Their
      approach is suitable for the publication of papers whose message relies on
      computation. Stated quite simply, Gentleman and Temple Lang (2003) propose a
      paradigm where documents are mixtures of code and text. Such documents may be
      self-contained or they may be a component of a compendium which provides the
      infrastructure needed to provide access to data and supporting software. These
      documents, or compendiums, can be processed in a number of different ways. One
      transformation will be to replace the code with its output -- thereby providing
      the familiar, but limited, static document. <p /> In this paper we apply these
      concepts to a seminal paper in bioinformatics, namely The Molecular
      Classification of Cancer, Golub et al (1999). The authors of that paper have
      generously provided data and other information that have allowed us to largely
      reproduce their results. Rather than reproduce this paper exactly we demonstrate
      that such a reproduction is possible and instead concentrate on demonstrating the
      usefulness of the compendium concept itself.

PMID- 16646838
TI  - Continuous covariates in genetic association studies of case-parent triads: gene
      and gene-environment interaction effects, population stratification, and power
      analysis.
AB  - We propose a multinomial logistic regression method which permits estimation and
      likelihood ratio tests for allele effects, their interactions with continuous
      covariates, and assessment of the degree of population stratification in genetic
      association studies of case-parent triads. Our approach overcomes the constraint
      imposed by the categorical nature of explanatory variables in the log-linear
      model. We also demonstrate that the multinomial logistic method can yield
      efficient inference in the presence of missing parental genotype data via the use
      of the Expectation-Maximization (EM) algorithm. We performed simulations to
      compare the multinomial logistic model with the case-pseudosibling conditional
      logistic model approach, both of which permit the incorporation of continuous
      covariates. Simulation results indicate that the multinomial logistic model and
      the conditional logistic model lead to similar estimates in large samples. A
      simulation-based method of sample size estimation is also used to show that the
      two models are approximately equivalent in sample size requirements. When
      parental genotype data are missing, either completely at random or dependent on
      covariates, the use of the EM algorithm gives multinomial logistic model greater
      power. Since the multinomial logistic model offers the possibility of assessing
      the degree of population stratification in the sample and can also provide
      efficient inference in the presence of missing parental genotypes, the proposed
      model has an important application in epidemiological family-based association
      studies.

PMID- 16646839
TI  - Robust remote homology detection by feature based Profile Hidden Markov Models.
AB  - The detection of remote homologies is of major importance for molecular biology
      applications like drug discovery. The problem is still very challenging even for
      state-of-the-art probabilistic models of protein families, namely Profile HMMs.
      In order to improve remote homology detection we propose feature based semi
      continuous Profile HMMs. Based on a richer sequence representation consisting of
      features which capture the biochemical properties of residues in their local
      context, family specific semi-continuous models are estimated completely data
      driven. Additionally, for substantially reducing the number of false predictions
      an explicit rejection model is estimated. Both the family specific semi
      continuous Profile HMM and the non-target model are competitively evaluated. In
      the experimental evaluation of superfamily based screening of the SCOP database
      we demonstrate that semi-continuous Profile HMMs significantly outperform their
      discrete counterparts. Using the rejection model the number of false positive
      predictions could be reduced substantially which is an important prerequisite for
      target identification applications.

PMID- 16646840
TI  - Empirical bayes estimation of a sparse vector of gene expression changes.
AB  - Gene microarray technology is often used to compare the expression of thousand of
      genes in two different cell lines. Typically, one does not expect measurable
      changes in transcription amounts for a large number of genes; furthermore, the
      noise level of array experiments is rather high in relation to the available
      number of replicates. For the purpose of statistical analysis, inference on the
      "population'' difference in expression for genes across the two cell lines is
      often cast in the framework of hypothesis testing, with the null hypothesis being
      no change in expression. Given that thousands of genes are investigated at the
      same time, this requires some multiple comparison correction procedure to be in
      place. We argue that hypothesis testing, with its emphasis on type I error and
      family analogues, may not address the exploratory nature of most microarray
      experiments. We instead propose viewing the problem as one of estimation of a
      vector known to have a large number of zero components. In a Bayesian framework,
      we describe the prior knowledge on expression changes using mixture priors that
      incorporate a mass at zero, and we choose a loss function that favors the
      selection of sparse solutions. We consider two different models applicable to the
      microarray problem, depending on the nature of replicates available, and show how
      to explore the posterior distributions of the parameters using MCMC. Simulations
      show an interesting connection between this Bayesian estimation framework and
      false discovery rate (FDR) control. Finally, two empirical examples illustrate
      the practical advantages of this Bayesian estimation paradigm.

PMID- 16646841
TI  - Hierarchical inverse Gaussian models and multiple testing: application to gene
      expression data.
AB  - Detecting differentially expressed genes in microarray experiments is a topic
      that has been well studied in the literature. Many hypothesis testing methods
      have been proposed that rely on strong distributional assumptions for the gene
      intensities. However, the shape of microarray data may vary substantially from
      one experiment to another, and model assumptions may be seriously violated in
      many cases. The literature on microarray data is mainly based on two
      distributions: the log-normal and the gamma distributions, that often appear to
      be effective when used in a Bayesian hierarchical framework. However, if a model
      that fits the data well in a global manner seems attractive, two points should be
      regarded with attention: the ability of the model to fit the tail of the observed
      distribution, and its robustness to a wrong specification of the model, in terms
      of error rates for the hypothesis tests. In order to focus on these aspects, we
      propose to use Bayesian models involving the inverse Gaussian distribution to
      describe gene expression data. We show that these models can be good competitors
      to the traditional Bayesian or random effect gamma or log-normal models in some
      situations. A multiple testing procedure is then proposed, based on an asymptotic
      property of the posterior probability of the one-sided alternative hypothesis. We
      show that the asymptotic property is well approximated for inverse Gaussian
      models, even when the number of observations available for each test is very
      small.

PMID- 16646842
TI  - FADO: a statistical method to detect favored or avoided distances between
      occurrences of motifs using the Hawkes' model.
AB  - We propose an original statistical method to estimate how the occurrences of a
      given process along a genome, genes or motifs for instance, may be influenced by
      the occurrences of a second process. More precisely, the aim is to detect avoided
      and/or favored distances between two motifs, for instance, suggesting possible
      interactions at a molecular level. For this, we consider occurrences along the
      genome as point processes and we use the so-called Hawkes' model. In such model,
      the intensity at position t depends linearly on the distances to past occurrences
      of both processes via two unknown profile functions to estimate. We perform a non
      parametric estimation of both profiles by using B-spline decompositions and a
      constrained maximum likelihood method. Finally, we use the AIC criterion for the
      model selection. Simulations show the excellent behavior of our estimation
      procedure. We then apply it to study (i) the dependence between gene occurrences
      along the E. coli genome and the occurrences of a motif known to be part of the
      major promoter for this bacterium, and (ii) the dependence between the yeast S.
      cerevisiae genes and the occurrences of putative polyadenylation signals. The
      results are coherent with known biological properties or previous predictions,
      meaning this method can be of great interest for functional motif detection, or
      to improve knowledge of some biological mechanisms.

PMID- 16646843
TI  - Prediction of genomewide conserved epitope profiles of HIV-1: classifier choice
      and peptide representation.
AB  - Identification of peptides binding to Major Histocompatibility Complex (MHC)
      molecules is important for accelerating vaccine development and improving
      immunotherapy. Accordingly, a wide variety of prediction methods have been
      applied in this context. In this paper, we introduce (tree-based) ensemble
      classifiers for such problems and contrast their predictive performance with
      forefront existing methods for both MHC class I and class II molecules. In
      addition, we investigate the impact of differing peptide representation schemes
      on performance. Finally, classifier predictions are used to conduct genomewide
      scans of a diverse collection of HIV-1 strains, enabling assessment of epitope
      conservation. We investigated all combinations of six classification methods
      (classification trees, artificial neural networks, support vector machines, as
      well as the more recently devised ensemble methods (bagging, random forests,
      boosting) with four peptide representation schemes (amino acid sequence, select
      biophysical properties, select quantitative structure-activity relationship
      (QSAR) descriptors, and the combination of the latter two) in predicting peptide
      binding to an MHC class I molecule (HLA-A2) and MHC class II molecule (HLA-DR4).
      Our results show that the ensemble methods are consistently more accurate than
      the other three alternatives. Furthermore, they are robust with respect to
      parameter tuning. Among the four representation schemes, the amino acid sequence
      representation gave consistently (across classifiers) best results. This finding
      obviates the need for feature selection strategies incurred by use of biophysical
      and/or QSAR properties. We obtained, and aligned, a diverse set of 32 HIV-1
      genomes and pursued genomewide HLA-DR4 epitope profiling by querying with respect
      to classifier predictions, as obtained under each of the four peptide
      representation schemes. We validated those epitopes conserved across strains
      against known T-cell epitopes. Once again, amino acid sequence representation was
      at least as effective as using properties. Assessment of novel epitope
      predictions awaits experimental verification.

PMID- 16646844
TI  - Fold-change estimation of differentially expressed genes using mixture mixed
      model.
AB  - Microarray experiments produce expression measurements for thousands of genes
      simultaneously, though usually for a small number of RNA samples. The most common
      problem is the identification of genes that are differentially expressed between
      different groups of samples or biological conditions. As the number of genes far
      exceeds the number of RNA samples, the inherent multiplicity poses a severe
      problem in both hypothesis testing and effect estimation. While much of the
      recent literature is focused on the hypothesis aspects, we concentrate in this
      paper on effect estimation as a tool for the identification of differentially
      expressed genes. We propose a linear mixed model where the random effects are
      assumed to follow a mixture distribution, and study in detail the case of three
      normals, corresponding to genes that are down-, up- or non regulated. Our
      approach leads to a new type of non-linear shrinkage estimation, where a
      proportion of estimates is shrunk to zero, while the rest follows standard linear
      shrinkage. This allows us to estimate the log fold-change of the genes involved
      and to identify those that are differentially expressed within the same model
      framework. We investigate the operating characteristics of our method using
      simulation and spike-in studies, and illustrate its application to real data
      using a breast-cancer dataset.

PMID- 16646845
TI  - Test on the structure of biological sequences via Chaos Game Representation.
AB  - In this paper biological sequences are modelled by stationary ergodic sequences.
      A new family of statistical tests to characterize the randomness of the inputs is
      proposed and analyzed. Tests for independence and for the determination of the
      appropriate order of a Markov chain are constructed with the Chaos Game
      Representation (CGR), and applied to several genomes.

PMID- 16646846
TI  - Reverse engineering galactose regulation in yeast through model selection.
AB  - We examine the application of statistical model selection methods to reverse
      engineering the control of galactose utilization in yeast from DNA microarray
      experiment data. In these experiments, relationships among gene expression values
      are revealed through modifications of galactose sugar level and genetic
      perturbations through knockouts. For each gene variable, we select predictors
      using a variety of methods, taking into account the variance in each measurement.
      These methods include maximization of log-likelihood with Cp, AIC, and BIC
      penalties, bootstrap and cross-validation error estimation, and coefficient
      shrinkage via the Lasso.

PMID- 16646847
TI  - Empirical Bayes and resampling based multiple testing procedure controlling tail
      probability of the proportion of false positives.
AB  - Simultaneously testing a collection of null hypotheses about a data generating
      distribution based on a sample of independent and identically distributed
      observations is a fundamental and important statistical problem involving many
      applications. In this article we propose a new re-sampling based multiple testing
      procedure asymptotically controlling the probability that the proportion of false
      positives among the set of rejections exceeds q at level alpha, where q and alpha
      are user supplied numbers. The procedure involves 1) specifying a conditional
      distribution for a guessed set of true null hypotheses, given the data, which
      asymptotically is degenerate at the true set of null hypotheses, and 2)
      specifying a generally valid null distribution for the vector of test-statistics
      proposed in Pollard & van der Laan (2003), and generalized in our subsequent
      article Dudoit, van der Laan, & Pollard (2004), van der Laan, Dudoit, & Pollard
      (2004), and van der Laan, Dudoit, & Pollard (2004b). Ingredient 1) is established
      by fitting the empirical Bayes two component mixture model (Efron (2001b)) to the
      data to obtain an upper bound for marginal posterior probabilities of the null
      being true, given the data. We establish the finite sample rational behind our
      proposal, and prove that this new multiple testing procedure asymptotically
      controls the wished tail probability for the proportion of false positives under
      general data generating distributions. In addition, we provide simulation studies
      establishing that this method is generally more powerful in finite samples than
      our previously proposed augmentation multiple testing procedure (van der Laan,
      Dudoit, & Pollard (2004b)) and competing procedures from the literature. Finally,
      we illustrate our methodology with a data analysis.

PMID- 16646848
TI  - Generalized rank tests for replicated microarray data.
AB  - Gene expression data from microarray experiments have been studied using several
      statistical models. Significance Analysis of Microarrays (SAM), for example, has
      proved to be useful in analyzing microarray data. In the spirit of the SAM
      procedures, we develop permutation based rank-tests for generalized Wilcoxon
      ranksum test for two-group comparisons of replicated microarray data. Also, for
      microarray experiments with randomized block design, we consider generalized
      signed rank test. The statistical analysis software package is written in R and
      is freely available in a package.

PMID- 16646849
TI  - Weighted analysis of paired microarray experiments.
AB  - In microarray experiments quality often varies, for example between samples and
      between arrays. The need for quality control is therefore strong. A statistical
      model and a corresponding analysis method is suggested for experiments with
      pairing, including designs with individuals observed before and after treatment
      and many experiments with two-colour spotted arrays. The model is of mixed type
      with some parameters estimated by an empirical Bayes method. Differences in
      quality are modelled by individual variances and correlations between
      repetitions. The method is applied to three real and several simulated datasets.
      Two of the real datasets are of Affymetrix type with patients profiled before and
      after treatment, and the third dataset is of two-colour spotted cDNA type. In all
      cases, the patients or arrays had different estimated variances, leading to
      distinctly unequal weights in the analysis. We suggest also plots which
      illustrate the variances and correlations that affect the weights computed by our
      analysis method. For simulated data the improvement relative to previously
      published methods without weighting is shown to be substantial.

PMID- 16646850
TI  - A probabilistic approach to large-scale association scans: a semi-Bayesian method
      to detect disease-predisposing alleles.
AB  - Recent analytic and technological breakthroughs have set the stage for genome
      wide linkage disequilibrium studies to map disease-susceptibility variants. This
      paper discusses a probabilistic methodology for making disease-mapping inferences
      in large-scale case-control genetic studies. The semi-Bayesian approach promoted
      compares the probability of the observed data under disease hypotheses to the
      probability of the data under a null hypothesis defined by data at all the
      markers interrogated in a large study. This method automatically adjusts for the
      effects of diffuse population stratification. It is claimed that this
      characterization of the evidence for or against disease models may facilitate
      more appropriate inductions for large-scale genetic studies. Results include (i)
      an analytic solution for the population stratification-adjusted Bayes' factor,
      (ii) the relationship between sample size and Bayes' factors, (iii) an extension
      to an approximate Bayes' factor calculated across closely-linked sites, and (iv)
      an extension across multiple studies. Although this paper deals exclusively with
      genetic studies, it is possible to generalize the approach to treat many
      different large-scale experiments including studies of gene expression and
      proteomics.

PMID- 16646851
TI  - A shrinkage approach to large-scale covariance matrix estimation and implications
      for functional genomics.
AB  - Inferring large-scale covariance matrices from sparse genomic data is an
      ubiquitous problem in bioinformatics. Clearly, the widely used standard
      covariance and correlation estimators are ill-suited for this purpose. As
      statistically efficient and computationally fast alternative we propose a novel
      shrinkage covariance estimator that exploits the Ledoit-Wolf (2003) lemma for
      analytic calculation of the optimal shrinkage intensity. Subsequently, we apply
      this improved covariance estimator (which has guaranteed minimum mean squared
      error, is well-conditioned, and is always positive definite even for small sample
      sizes) to the problem of inferring large-scale gene association networks. We show
      that it performs very favorably compared to competing approaches both in
      simulations as well as in application to real expression data.

PMID- 16646852
TI  - Structured antedependence models for functional mapping of multiple longitudinal
      traits.
AB  - In this article, we present a statistical model for mapping quantitative trait
      loci (QTL) that determine growth trajectories of two correlated traits during
      ontogenetic development. This model is derived within the maximum likelihood
      context, incorporated by mathematical aspects of growth processes to model the
      mean vector and by structured antedependence (SAD) models to approximate time
      dependent covariance matrices for longitudinal traits. It provides a quantitative
      framework for testing the relative importance of two mechanisms, pleiotropy and
      linkage, in contributing to genetic correlations during ontogeny. This model has
      been employed to map QTL affecting stem height and diameter growth trajectories
      in an interspecific hybrid progeny of Populus, leading to the successful
      discovery of three pleiotropic QTL on different linkage groups. The implications
      of this model for genetic mapping within a broader context are discussed.

PMID- 16646853
TI  - Correlation between gene expression levels and limitations of the empirical bayes
      methodology for finding differentially expressed genes.
AB  - Stochastic dependence between gene expression levels in microarray data is of
      critical importance for the methods of statistical inference that resort to
      pooling test statistics across genes. The empirical Bayes methodology in the
      nonparametric and parametric formulations, as well as closely related methods
      employing a two-component mixture model, represent typical examples. It is
      frequently assumed that dependence between gene expressions (or associated test
      statistics) is sufficiently weak to justify the application of such methods for
      selecting differentially expressed genes. By applying resampling techniques to
      simulated and real biological data sets, we have studied a potential impact of
      the correlation between gene expression levels on the statistical inference based
      on the empirical Bayes methodology. We report evidence from these analyses that
      this impact may be quite strong, leading to a high variance of the number of
      differentially expressed genes. This study also pinpoints specific components of
      the empirical Bayes method where the reported effect manifests itself.

PMID- 16646854
TI  - Bayesian statistical studies of the Ramachandran distribution.
AB  - We describe a method for the generation of knowledge-based potentials and apply
      it to the observed torsional angles of known protein structures. The potential is
      derived using Bayesian reasoning, and is useful as a prior for further such
      reasoning in the presence of additional data. The potential takes the form of a
      probability density function, which is described by a small number of
      coefficients with the number of necessary coefficients determined by tests based
      on statistical significance and entropy. We demonstrate the methods in deriving
      one such potential corresponding to two dimensions, the Ramachandran plot. In
      contrast to traditional histogram-based methods, the function is continuous and
      differentiable. These properties allow us to use the function as a force term in
      the energy minimization of appropriately described structures. The method can
      easily be extended to other observable angles and higher dimensions, or to
      include sequence dependence and should find applications in structure
      determination and validation.

PMID- 16646855
TI  - On reference designs for microarray experiments.
AB  - We compare four variants of the reference design for microarray experiments in
      terms of their relative efficiency. A common reference sample across arrays is
      the most extensively used variation in practice, but independent samples from a
      reference group have also been considered in previous works. The relative
      efficiency of these designs depends of the number of treatments and the ratio
      between biological and technical variances. Here, we propose another alternative
      of reference structure, denoted by blocked reference design (BRD), in which each
      set (replication) of the treated samples is co-hybridized to an independent
      experimental unit of the control (reference) group. We provide efficiency curves
      for each pair of designs under different scenarios of variance ratio and number
      of treatments groups. The results show that the BRD is more efficient and less
      expensive than the traditional reference designs. Among the situations where the
      BRD is likely to be preferable we list time course experiments with a baseline
      and drug experiments with a placebo group.

PMID- 16646856
TI  - Computing asymptotic power and sample size for case-control genetic association
      studies in the presence of phenotype and/or genotype misclassification errors.
AB  - It is well established that phenotype and genotype misclassification errors
      reduce the power to detect genetic association. Resampling a subset of the data
      (e.g, double-sampling) of genotype and/or phenotype with a gold standard
      measurement is one method to address this issue. We derive the non-centrality
      parameter (NCP) for the recently published Likelihood Ratio Test Allowing for
      Error (LRTae) in the presence of random phenotype and genotype errors. With the
      NCP, power and sample size can be analytically determined at any significance
      level. We verify analytic power with simulations using a 2**k factorial design
      given high and low settings of: case and control genotype frequencies, phenotype
      and genotype misclassification probabilities, total sample size, ratio of cases
      to controls, and proportions of phenotype and/or genotype double-samples. We also
      perform example applications of our method assuming equal costs for the LRTae
      method and the standard method that does not use double-sample information
      (LRTstd) to determine if power gain due to double-sampling a proportion of
      samples outweighs the reduction in sample size due to additional costs in
      obtaining double-samples. Our results showed a median difference of at most 0.01
      between analytic and simulation power for the factorial design settings, with
      maximum difference of 0.054. For our cost/benefits analysis calculations, results
      for genotype errors are that double-sampling appears most beneficial (in terms of
      power gain) when cost of double-sampling is relatively low, irrespective of the
      proportion of individuals double-sampled. In the presence of phenotype error,
      there is always power gain using the LRTae method for the parameter settings
      considered. We have freely available software that performs power and sample size
      calculations for the LRTae method and cost/benefits analyses comparing power for
      LRTae and LRTstd methods assuming equal costs.

PMID- 16646857
TI  - Stepwise normalization of two-channel spotted microarrays.
AB  - Intensities measurements of spotted microarrays embody many undesirable
      systematic variations. Very commonly, varying amounts and types of such
      variations are observed in different arrays. Although various normalization
      methods have been proposed to remove such systematic effects, it has not been
      well studied how to assess or select the most appropriate method for different
      arrays and data sets. To address this issue, we present a novel normalization
      technique, STEPNORM, for data-dependent and adaptive normalization of two-channel
      spotted microarrays. STEPNORM performs a stepwise interrogation of a range of
      different normalization models and selects the appropriate method based on formal
      model selection criteria. In addition, we evaluate the effectiveness of STEPNORM
      and other commonly used normalization methods utilizing a set of specially
      constructed splicing arrays.

PMID- 16646858
TI  - Comparing automatic and manual image processing in FLARE assay analysis for colon
      carcinogenesis.
AB  - Measurement of the amount of oxidative damage to DNA is one tool that can be used
      to estimate the beneficial effect of diet on the prevention of colon
      carcinogenesis. The FLARE assay is a modification of the single-cell gel
      electrophoresis (Comet) assay, and provides a measure of the 8OHdG adduct in the
      cells. In this paper, we present two innovations to the existing methods of
      analysis. The first one is related to the FLARE assay itself. We describe
      automated image analysis techniques that can be expected to measure oxidative
      damage faster, reproducibly, with less noise, and hence achieve greater
      statistical power. The proposed technique is compared to an existing technique,
      which was more manual and thus slower. The second innovation is our statistical
      analysis: we exploit the shape of FLARE intensity histograms, and show
      statistically significant diet effects in the duodenum. Previous analyses of this
      data concentrated on simple summary statistics, and found only marginally
      statistically significant diet effects. With the new imaging method and measure
      of oxidative damage, we show cells in the duodenum exposed to fish oil as having
      more oxidative damage than cells exposed to corn oil.

PMID- 16646859
TI  - Pixel-level signal modelling with spatial correlation for two-colour microarrays.
AB  - Statistical models for spot shapes and signal intensities are used in image
      analysis of laser scans of microarrays. Most models have essentially been based
      on the assumption of independent pixel intensity values, but models that allow
      for spatial correlation among neighbouring pixels can accommodate errors in the
      microarray slide and should improve the model fit. Five spatial correlation
      structures, exponential, Gaussian, linear, rational quadratic and spherical, are
      compared for a dataset with 50-mer two-colour oligonucleotide microarrays and 452
      probes for selected Arabidopsis genes. Substantial improvement in model fit is
      obtained for all five correlation structures compared to the model with
      independent pixel values, and the Gaussian and the spherical models seem to be
      slightly better than the other three models. We also conclude that for the data
      set analysed the correlation seems negligible for non-neighbouring pixels.

PMID- 16646860
TI  - Empirical bayes microarray ANOVA and grouping cell lines by equal expression
      levels.
AB  - In the exploding field of gene expression techniques such as DNA microarrays,
      there are still few general probabilistic methods for analysis of variance.
      Linear models and ANOVA are heavily used tools in many other disciplines of
      scientific research. The usual F-statistic is unsatisfactory for microarray data,
      which explore many thousand genes in parallel, with few replicates. We present
      three potential one-way ANOVA statistics in a parametric statistical framework.
      The aim is to separate genes that are differently regulated across several
      treatment conditions from those with equal regulation. The statistics have
      different features and are evaluated using both real and simulated data. Our
      statistic B1 generally shows the best performance, and is extended for use in an
      algorithm that groups cell lines by equal expression levels for each gene. An
      extension is also outlined for more general ANOVA tests including several
      factors. The methods presented are implemented in the freely available
      statistical language R. They are available at
      http://www.math.uu.se/staff/pages/?uname=ingrid.

PMID- 16646861
TI  - Multiple testing and data adaptive regression: an application to HIV-1 sequence
      data.
AB  - Analysis of viral strand sequence data and viral replication capacity could
      potentially lead to biological insights regarding the replication ability of HIV
      1. Determining specific target codons on the viral strand will facilitate the
      manufacturing of target-specific antiretrovirals. Various algorithmic and
      analysis techniques can be applied to this application. In this paper, we apply
      two techniques to a data set consisting of 317 patients, each with 282 sequenced
      protease and reverse transcriptase codons. The first application is recently
      developed multiple testing procedures to find codons which have significant
      univariate associations with the replication capacity of the virus. A single-step
      multiple testing procedure (Pollard and van der Laan 2003) method was used to
      control the family wise error rate (FWER) at the five percent alpha level as well
      as the application of augmentation multiple testing procedures to control the
      generalized family wise error (gFWER) or the tail probability of the proportion
      of false positives (TPPFP). We also applied a data adaptive multiple regression
      algorithm to obtain a prediction of viral replication capacity based on an entire
      mutant/non-mutant sequence profile. This is a loss-based, cross-validated
      Deletion/Substitution/Addition regression algorithm (Sinisi and van der Laan
      2004), which builds candidate estimators in the prediction of a univariate
      outcome by minimizing an empirical risk. These methods are two separate
      techniques with distinct goals used to analyze this structure of viral data.

PMID- 16646862
TI  - Early diagnostic marker panel determination for microarray based clinical
      studies.
AB  - We present a novel, cost efficient two-phase design for predictive clinical gene
      expression studies: early marker panel determination (EMPD). In Phase-1, genome
      wide microarrays are used only for a small number of individual patient samples.
      From this Phase-1 data a panel of marker genes is derived. In Phase-2, the
      expression values of these marker panel genes are measured for a large group of
      patients and a predictive classification model is learned from this data. Phase-2
      does not require the use of expensive whole genome microarrays, thus making EMPD
      a cost efficient alternative for current trials. The expected performance loss of
      EMPD is compared to designs which use genome-wide microarrays for all patients.
      We also examine the trade-off between the number of patients included in Phase-1
      and the number of marker genes required in Phase-2. By analysis of five published
      datasets we find that in Phase-1 already 16 patients per group are sufficient to
      determine a suitable marker panel of 10 genes, and that this early decision
      compromises the final performance only marginally.

PMID- 16646863
TI  - Low-order conditional independence graphs for inferring genetic networks.
AB  - As a powerful tool for analyzing full conditional (in-)dependencies between
      random variables, graphical models have become increasingly popular to infer
      genetic networks based on gene expression data. However, full (unconstrained)
      conditional relationships between random variables can be only estimated
      accurately if the number of observations is relatively large in comparison to the
      number of variables, which is usually not fulfilled for high-throughput genomic
      data. Recently, simplified graphical modeling approaches have been proposed to
      determine dependencies between gene expression profiles. For sparse graphical
      models such as genetic networks, it is assumed that the zero- and first-order
      conditional independencies still reflect reasonably well the full conditional
      independence structure between variables. Moreover, low-order conditional
      independencies have the advantage that they can be accurately estimated even when
      having only a small number of observations. Therefore, using only zero- and first
      order conditional dependencies to infer the complete graphical model can be very
      useful. Here, we analyze the statistical and probabilistic properties of these
      low-order conditional independence graphs (called 0-1 graphs). We find that for
      faithful graphical models, the 0-1 graph contains at least all edges of the full
      conditional independence graph (concentration graph). For simple structures such
      as Markov trees, the 0-1 graph even coincides with the concentration graph.
      Furthermore, we present some asymptotic results and we demonstrate in a
      simulation study that despite their simplicity, 0-1 graphs are generally good
      estimators of sparse graphical models. Finally, the biological relevance of some
      applications is summarized.

PMID- 16646864
TI  - Quality optimised analysis of general paired microarray experiments.
AB  - In microarray experiments, several steps may cause sub-optimal quality and the
      need for quality control is strong. Often the experiments are complex, with
      several conditions studied simultaneously. A linear model for paired microarray
      experiments is proposed as a generalisation of the paired two-sample method by
      Kristiansson et al. (2005). Quality variation is modelled by different variance
      scales for different (pairs of) arrays, and shared sources of variation are
      modelled by covariances between arrays. The gene-wise variance estimates are
      moderated in an empirical Bayes approach. Due to correlations all data is
      typically used in the inference of any linear combination of parameters. Both
      real and simulated data are analysed. Unequal variances and strong correlations
      are found in real data, leading to further examination of the fit of the model
      and of the nature of the datasets in general. The empirical distributions of the
      test-statistics are found to have a considerably improved match to the null
      distribution compared to previous methods, which implies more correct p-values
      provided that most genes are non-differentially expressed. In fact, assuming
      independent observations with identical variances typically leads to optimistic p
      values. The method is shown to perform better than the alternatives in the
      simulation study.

PMID- 16646865
TI  - Issues of processing and multiple testing of SELDI-TOF MS proteomic data.
AB  - A new data filtering method for SELDI-TOF MS proteomic spectra data is described.
      We examined technical repeats (2 per subject) of intensity versus m/z
      (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia
      patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As
      others have noted, the type of data processing as well as experimental
      variability can have a disproportionate impact on the list of "interesting''
      proteins (see Baggerly et al. (2004)). We propose a list of processing and
      multiple testing techniques to correct for 1) background drift; 2) filtering
      using smooth regression and cross-validated bandwidth selection; 3) peak finding;
      and 4) methods to correct for multiple testing (van der Laan et al. (2005)). The
      result is a list of proteins (indexed by m/z) where average expression is
      significantly different among disease (or treatment, etc.) groups. The procedures
      are intended to provide a sensible and statistically driven algorithm, which we
      argue provides a list of proteins that have a significant difference in
      expression. Given no sources of unmeasured bias (such as confounding of
      experimental conditions with disease status), proteins found to be statistically
      significant using this technique have a low probability of being false positives.

PMID- 16646866
TI  - A generalized clustering problem, with application to DNA microarrays.
AB  - We think of cluster analysis as class discovery. That is, we assume that there is
      an unknown mapping called clustering structure that assigns a class label to each
      observation, and the goal of cluster analysis is to estimate this clustering
      structure, that is, to estimate the number of clusters and cluster assignments.
      In traditional cluster analysis, it is assumed that such unknown mapping is
      unique. However, since the observations may cluster in more than one way
      depending on the variables used, it is natural to permit the existence of more
      than one clustering structure. This generalized clustering problem of estimating
      multiple clustering structures is the focus of this paper. We propose an
      algorithm for finding multiple clustering structures of observations which
      involves clustering both variables and observations. The number of clustering
      structures is determined by the number of variable clusters. The dissimilarity
      measure for clustering variables is based on nearest-neighbor graphs. The
      observations are clustered using weighted distances with weights determined by
      the clusters of the variables. The motivating application is to gene expression
      data.

PMID- 16646867
TI  - A Bayes regression approach to array-CGH data.
AB  - This paper develops a Bayes regression model having change points for the
      analysis of array-CGH data by utilizing not only the underlying spatial structure
      of the genomic alterations but also the observation that the noise associated
      with the ratio of the fluorescence intensities is bigger when the intensities get
      smaller. We show that this Bayes regression approach is particularly suitable for
      the analysis of cDNA microarray-CGH data, which are generally noisier than those
      using genomic clones. A simulation study and a real data analysis are included to
      illustrate this approach.

PMID- 16646868
TI  - Statistical selection of maintenance genes for normalization of gene expressions.
AB  - Maintenance genes can be used for normalization in the comparison of gene
      expressions. Even though the absolute expression levels of maintenance genes may
      vary considerably among different tissues or cells, a set of maintenance genes
      may provide suitable normalization if their expression levels are relatively
      constant in the specific tissues or cells of interest. A statistical procedure is
      proposed to select maintenance genes for normalization of gene expression data
      from tissues or cells of interest. This procedure is based on simultaneous
      confidence intervals for practical equivalence of relative gene expressions in
      these tissues or cells. As an illustration, the procedure is applied to the
      maintenance gene expression data from Vandesompele et al. (2002).

PMID- 16646869
TI  - Predicting the strongest domain-domain contact in interacting protein pairs.
AB  - Experiments to determine the complete 3-dimensional structures of protein
      complexes are difficult to perform and only a limited range of such structures
      are available. In contrast, large-scale screening experiments have identified
      thousands of pairwise interactions between proteins, but such experiments do not
      produce explicit structural information. In addition, the data produced by these
      high through-put experiments contain large numbers of false positive results, and
      can be biased against detection of certain types of interaction. Several methods
      exist that analyse such pairwise interaction data in terms of the constituent
      domains within proteins, scoring pairs of domain superfamilies according to their
      propensity to interact. These scores can be used to predict the strongest domain
      domain contact (the contact with the largest surface area) between interacting
      proteins for which the domain-level structures of the individual proteins are
      known. We test this predictive approach on a set of pairwise protein interactions
      taken from the Protein Quaternary Structure (PQS) database for which the true
      domain-domain contacts are known.While the overall prediction success rate across
      the whole test data set is poor, we shown how interactions in the test data set
      for which the training data are not informative can be automatically excluded
      from the prediction process, giving improved prediction success rates at the
      expense of restricted coverage of the test data.

PMID- 16646870
TI  - Dimension reduction for classification with gene expression microarray data.
AB  - An important application of gene expression microarray data is classification of
      biological samples or prediction of clinical and other outcomes. One necessary
      part of multivariate statistical analysis in such applications is dimension
      reduction. This paper provides a comparison study of three dimension reduction
      techniques, namely partial least squares (PLS), sliced inverse regression (SIR)
      and principal component analysis (PCA), and evaluates the relative performance of
      classification procedures incorporating those methods. A five-step assessment
      procedure is designed for the purpose. Predictive accuracy and computational
      efficiency of the methods are examined. Two gene expression data sets for tumor
      classification are used in the study.

PMID- 16646871
TI  - A new type of stochastic dependence revealed in gene expression data.
AB  - Modern methods of microarray data analysis are biased towards selecting those
      genes that display the most pronounced differential expression. The magnitude of
      differential expression does not necessarily indicate biological significance and
      other criteria are needed to supplement the information on differential
      expression. Three large sets of microarray data on childhood leukemia were
      analyzed by an original method introduced in this paper. A new type of stochastic
      dependence between expression levels in gene pairs was deciphered by our
      analysis. This modulation-like unidirectional dependence between expression
      signals arises when the expression of a "gene-modulator'' is stochastically
      proportional to that of a "gene-driver''. A total of more than 35% of all pairs
      formed from 12550 genes were conservatively estimated to belong to this type.
      There are genes that tend to form Type A relationships with the overwhelming
      majority of genes. However, this picture is not static: the composition of Type A
      gene pairs may undergo dramatic changes when comparing two phenotypes. The
      ability to identify genes that act as ;;modulators'' provides a potential
      strategy of prioritizing candidate genes.

PMID- 16646872
TI  - A new order estimator for fixed and variable length Markov models with
      applications to DNA sequence similarity.
AB  - Recently Peres and Shields discovered a new method for estimating the order of a
      stationary fixed order Markov chain. They showed that the estimator is consistent
      by proving a threshold result. While this threshold is valid asymptotically in
      the limit, it is not very useful for DNA sequence analysis where data sizes are
      moderate. In this paper we give a novel interpretation of the Peres-Shields
      estimator as a sharp transition phenomenon. This yields a precise and powerful
      estimator that quickly identifies the core dependencies in data. We show that it
      compares favorably to other estimators, especially in the presence of variable
      dependencies. Motivated by this last point, we extend the Peres-Shields estimator
      to Variable Length Markov Chains. We compare it to a well-established estimator
      and show that it is superior in terms of the predictive likelihood. We give an
      application to the problem of detecting DNA sequence similarity in plasmids.

PMID- 16646873
TI  - Treating expression levels of different genes as a sample in microarray data
      analysis: is it worth a risk?
AB  - One of the prevailing ideas in the literature on microarray data analysis is to
      pool the expression measures across genes and treat them as a sample drawn from
      some distribution. Several universal laws were proposed to analytically describe
      this distribution. This idea raises a number of concerns. The expression levels
      of genes are not identically distributed random variables so that treating them
      as a sample amounts to sampling from a mixture of equally weighted distributions,
      each being associated with a different gene. The expression levels of different
      genes are heavily dependent random variables so that the law of large numbers and
      statistical goodness-of-fit tests are normally inapplicable to this kind of data.
      This dependence represents a very serious pitfall in microarray data analysis.

PMID- 16646874
TI  - Using active learning in lecture: best of "both worlds".
AB  - Many creative teaching strategies have been developed in recent years in nursing
      and other fields to promote active learning. These strategies foster development
      of problem solving, critical thinking, and communication skills, and they
      encourage students to work collaboratively with peers. However, in nurse
      educators' rush to embrace active learning, lecture has been viewed negatively by
      some faculty. Rather than positioning active learning against lecture, another
      approach is to integrate active learning within lecture, gaining the benefits of
      both methods. An integrated approach also takes into consideration the situation
      of teaching large groups of students. This article examines benefits of an
      integrated approach to teaching and presents strategies for active learning
      intended for use with lecture.

PMID- 16646875
TI  - Beyond student ratings: peer observation of classroom and clinical teaching.
AB  - Peer observation of classroom and clinical teaching has received increased
      attention over the past decade in schools of nursing to augment student ratings
      of teaching effectiveness. One essential ingredient is the scale used to evaluate
      performance. A five-step systematic procedure for adapting, writing, and building
      any peer observation scale is described. The differences between the development
      of a classroom observation scale and an appraisal scale to observe clinical
      instructors are examined. Psychometric issues peculiar to observation scales are
      discussed in terms of content validity, eight types of response bias, and
      interobserver reliability. The applications of the scales in one school of
      nursing as part of the triangulation of methods with student ratings and the
      teaching portfolio are illustrated. Copies of the scales are also provided.

PMID- 16646876
TI  - Finding the way: a model for educational system analysis.
AB  - Administrators new to an academic setting experience a steep learning curve in
      finding their way around the organization. Leadership strategies that have proven
      effective in a previous setting or in another role may not be appropriate to or
      effective in the new setting. Disruptive effects of such leadership transitions
      can be minimized if newly employed administrators take a systematic approach to
      learning about the organization. The educational systems analysis model (ESAM)
      described here provides direction for new academic administrators in rapid
      analysis of a nursing education program. ESAM is comprised of both external and
      internal elements that influence system operation and the role of the
      administrator within the system. External elements include environmental factors
      that influence the program as well as the community of interest. Internal
      elements include the mission and goals, culture, relationships, structure,
      programs and services, resources, and outcomes of the program. Each of the
      internal elements is considered from both content and process perspectives.
      Relationships among the elements in the model are dynamic and reciprocal.

PMID- 16646877
TI  - Recreational music-making: an integrative group intervention for reducing burnout
      and improving mood states in first year associate degree nursing students:
      insights and economic impact.
AB  - The challenges of providing exemplary undergraduate nursing education cannot be
      underestimated in an era when burnout and negative mood states predictably lead
      to alarming rates of academic as well as career attrition. While the multi
      dimensional nature of this complex issue has been extensively elucidated, few
      rational strategies exist to reverse a disheartening trend recognizable early in
      the educational process that subsequently threatens to undermine the future
      viability of quality healthcare. This controlled prospective crossover study
      examined the impact of a 6-session Recreational Music-making (RMM) protocol on
      burnout and mood dimensions as well as Total Mood Disturbance (TMD) in first year
      associate level nursing students. A total of 75 first year associate degree
      nursing students from Allegany College of Maryland (ACM) participated in a 6
      session RMM protocol focusing on group support and stress reduction utilizing a
      specific group drumming protocol. Burnout and mood dimensions were assessed with
      the Maslach Burnout Inventory and the Profile of Mood States respectively.
      Statistically significant reductions of multiple burnout and mood dimensions as
      well as TMD scores were noted. Potential annual cost savings for the typical
      associate degree nursing program (16,800 dollars) and acute care hospital
      (322,000 dollars) were projected by an independent economic analysis firm. A cost
      effective 6-session RMM protocol reduces burnout and mood dimensions as well as
      TMD in associate degree nursing students.

PMID- 16646878
TI  - Evaluation framework for nursing education programs: application of the CIPP
      model.
AB  - It is advised that all nursing education programs conduct program evaluations to
      address accountability requirements and information for planning and guiding the
      delivery of the programs. Stufflebeam's CIPP Model, supported by triangulation of
      multiple modes of data collection provides such a theoretical framework for
      evaluations. This article proposes a total CIPP evaluation framework for nursing
      education programs. While this evaluation framework is applicable to any nursing
      evaluation program, it is practically useful for collaborative nursing programs
      as it allows a full assessment of each partner in its context. Under the
      direction of this author, the York-Seneca-Georgian-Durham collaborative BScN
      Program Evaluation Committee in Ontario developed and utilized a CIPP process
      evaluation.

PMID- 16646879
TI  - Building communities of scholars through a hologogy for online graduate nursing
      education: reconnecting with the wisdom of nursing.
AB  - Nursing must respond to complex health care needs, but the response will be
      ineffective without cohesiveness within the nursing community. Advance practice
      nursing students' exploration of the historical, philosophical, and theoretical
      structures of nursing can provide an anchor for study of the discipline, promote
      a feeling of connection with the community of nursing, and foster an
      understanding of the wisdom that exists within the body of nursing knowledge. The
      authors have developed and refined a structure and approach for teaching an
      online nursing theory course to promote students' identification with nursing
      knowledge and facilitate building a sense of community among the class members
      and with the discipline, as a whole. The purposes of this article are to describe
      this model for community building within a master's-level online graduate nursing
      theory course and to demonstrate student responses to the course process.

PMID- 16646880
TI  - Systematic reviews of health care interventions: an essential component of health
      sciences graduate programs.
AB  - Systematic reviews are an objective, rigorous assessment of both published and
      unpublished research that enable the reviewer to make recommendations to
      clinicians, policy-makers, consumers, and researchers. The steps in a systematic
      review include: (a) developing a research question, (b) developing relevance and
      validity tools, (c) conducting a thorough literature search of published and
      unpublished studies, (d) using relevance and validity tools to assess the
      studies, (e) completing data extraction for each study, (f) synthesizing the
      findings and, (g) writing the report. The purpose of this paper is to demonstrate
      the value of providing health science graduate students with the opportunity to
      learn about the conduct of a systematic review. An example of a thesis utilizing
      the method of a systematic review is presented.

PMID- 16646881
TI  - A study abroad experience in Guatemala: learning first-hand about health,
      education, and social welfare in a low-resource country.
AB  - The demographic characteristics of the United States are rapidly changing as the
      nation becomes more culturally, racially, and ethnically diverse. In light of
      these changes, it is increasingly important that health care professionals
      develop cultural competence and understanding. Study abroad experiences can help
      students learn first-hand about other cultures and can promote the development of
      enhanced cultural sensitivity and competence. Although there are many advantages
      and benefits of study-abroad experiences, these experiences also present unique
      challenges for both students and faculty. This article presents a description of
      a 3-credit elective study abroad course that was offered for graduate or
      undergraduate credit in the summer of 2003 in Guatemala, including a description
      of course objectives, the process of planning and implementing the course from
      the faculty's perspective, and one student's perceptions of her study abroad
      experience.

PMID- 16646882
TI  - Using standardized patients to teach and evaluate nurse practitioner students on
      cultural competency.
AB  - With the increasing diversity in the American population, it is imperative that
      nurse practitioners learn to manage patients with varying healthcare beliefs and
      needs. In order to develop culturally competent nurse practitioners, a number of
      methods have been developed. Many of the current methods focus on improving the
      awareness and knowledge of nurse practitioners regarding diverse populations.
      However, very few of the current programs focus on improving the skills and
      increasing the encounters the students have with diverse populations. This paper
      focuses on providing nurse practitioner students with diverse encounters using
      culturally enhanced standardized patient scenarios. The standardized patient
      programs provide nurse practitioner students with the opportunity to develop
      knowledge and skills related to cultural competency in a safe environment where
      the students can practice communication and physical assessment skills as they
      receive feedback from the patients they are seeing.

PMID- 16646883
TI  - Outcomes of master's education in nursing.
AB  - This qualitative, descriptive study examined changes in perspective experienced
      by 22 recent graduates of Master's in Nursing programs from three Ontario
      universities. Participants responded to semi-structured, taped interviews and
      recounted personal, practice, and attitudinal changes they could attribute to
      completing a Master's program in Nursing. Among outcomes were personal ones
      including greater self-confidence, credibility, and acuity of critical thinking.
      Deeper and broader world-views of the profession and health care were evident.
      All participants valued evidence-based practice, reporting greater use of
      multiple information sources. Participants communicated with other professionals
      on more equal terms and some described a multicultural function, translating
      knowledge between staff nurses and members of other disciplines. Pride in nursing
      and its potential for shaping health care was a recurring theme. More
      professional opportunities became available following Master's studies. The
      outcomes of this study contribute to understanding the effects of graduate
      education in nursing.

PMID- 16646884
TI  - Creating cohesion between the discipline and practice of nursing using Problem
      Based Learning.
AB  - For at least four decades there has been concern about the discontinuity between
      the discipline and practice of nursing. The learning traditions in nursing,
      including the traditional organization of professional educational curricula with
      an emphasis on general education, could be contributing to this discontinuity.
      Problem Based Learning (PBL) has been identified as one way to facilitate greater
      cohesion between the discipline and practice of nursing. Nursing learners exposed
      to PBL are challenged to achieve professionally desired liberal learning outcomes
      and acquire knowledge and skill in the discipline of nursing by encountering key
      professional practice situations as the stimulus and focus of their classroom
      learning activity. By combining reflection on existing knowledge essential to
      understanding the situation with research for new knowledge, PBL reflects the
      process of knowledge generation. Through PBL learners can achieve a deeper
      understanding of nursing as a discipline, the relationship of nursing to other
      disciplines and cohesion between the discipline and practice of nursing.

PMID- 16646885
TI  - How different can you be and still survive? Homogeneity and difference in
      clinical nursing education.
AB  - The article focuses on a component of a three-year institutional ethnography
      regarding the construction of cultural diversity in clinical education. Students
      in two Canadian schools of nursing described being a nursing student as bounded
      by unwritten and largely invisible expectations of homogeneity in the context of
      a predominant discourse of equality and cultural sensitivity. At the same time,
      they witnessed many incidents, both personally and those directed toward other
      individuals of the same culture, of clinical teachers problematizing difference
      and centering on difference as less than the expected norm. This complex and
      often contradictory experience of difference and homogeneity contributed to their
      construction of cultural diversity as a problem. The authors provide examples of
      how the perception of being different affected some students' learning in the
      clinical setting and their interactions with clinical teachers. They will
      illustrate that this occurred in the context of macro influences that shaped how
      both teachers and students experienced and perceived cultural diversity. The
      article concludes with a challenge to nurse educators to deconstruct their
      beliefs and assumptions about inclusivity in nursing education.

PMID- 16646886
TI  - Student experiences in web-based nursing courses: benchmarking best practices.
AB  - The purpose of this study, part of a larger benchmarking study, is to seek to
      confirm benchmarks for best practices for teaching and learning in web-based
      courses. Six hundred thirty-one responses to two open-ended questions from a
      survey of nursing students in undergraduate and graduate nursing programs at five
      participating schools were analyzed to understand the student experience and
      confirm the predetermined benchmarks. Using qualitative description, responses
      were analyzed using content analysis procedures. Students provided rich
      descriptions of the study benchmarks such as use of technology, active learning,
      feedback, respect for diversity, interaction with faculty and peers, convenience,
      access, professionalism, preference for face-to-face interaction, connectedness,
      and orientation to technology use. The students also identified additional
      student support variables such as the need for information about the course,
      orientation to using technology, and the importance of learning resources that
      should be considered as additional benchmarks for best practices in web-based
      courses.

PMID- 16646887
TI  - The meaning of participation in an international service experience among
      baccalaureate nursing students.
AB  - Nine nursing students volunteered their spring break to provide nursing service
      in a rural, economically challenged area of Guatemala. The students were involved
      in all aspects of planning and preparation for the international experience. All
      nine students participated in a qualitative study which sought to describe the
      meaning of participation in an international service experience among
      baccalaureate nursing students. Data were collected through reflection journals,
      evening group conversations in Guatemala, written narratives, and a post
      experience focus group interview. Six themes were uncovered using content
      analysis: (a) Clarification of career path/goals, (b) Improved understanding of
      social justice and globalization issues, (c) Motivation to continue service work,
      (d) Discovering the reciprocity of relationships with others, (e) Appreciation
      for the whole person, and (f) Finding a way to respect the sacredness of the
      experience. This study lends support for the positive benefits of short-term
      international experiences for nursing students.

PMID- 16646888
TI  - The impact of an urban outreach teaching project: developing cultural competence.
AB  - The purpose of this study was to explore the development of cultural competence
      in a group of university nursing students in the context of an interactive
      substance abuse prevention project attached to a health promotion course with 414
      racially diverse high school students. The project provided opportunities for
      contact, interaction, and reflection. A descriptive approach was utilized to
      elicit the meaning attached to the experience. Data included written content from
      an exit survey, field notes from onsite debriefings, transcriptions of a focus
      group interview, and an analysis of theoretical papers. Findings indicate that
      when university students participate in an urban teaching project under
      conditions of diminishing anxiety and are given opportunities for reflection,
      they not only increase cultural competence but they also develop a sense of
      advocacy. Recommendations are made for building community partnerships to enhance
      cultural competence.

PMID- 16646889
TI  - Use of a human simulator for undergraduate nurse education.
AB  - Use of a human patient simulator has been identified as an effective teaching
      strategy in many areas of the health care field. However, there is little
      information to help faculty learn the general principles of simulation. This
      article provides basic concepts to those anticipating simulator use. A guide for
      running a successful simulation is provided. A heart failure scenario is used as
      an example.

PMID- 16646890
TI  - Meeting the at-risk challenge: empowering nursing students through mentoring.
AB  - Wanting to improve student retention, progression, and graduation, the nursing
      faculty of the University of Nevada, Las Vegas developed a program for
      undergraduate students. Designated faculty mentors are available for academically
      at-risk students, or any student wanting to improve learning skills. Through
      mentoring sessions, students are helped to assess their learning difficulties,
      develop individualized prescription plans for learning, gain support during
      implementation of learning strategies, and evaluate results. Implemented in 2002,
      the program reflects positive outcomes. Of the 29 students who were referred to
      the program, only 3 were unsuccessful in passing their nursing courses. Student
      evaluations of the program reflect the value of the mentoring experience. The
      program has subsequently developed in the areas of advertising, diagnostic
      student testing, and student access to support resources.

PMID- 16646891
TI  - Philippine academic visit: brief but life-changing.
AB  - As one way of inculcating international perspectives in its graduates, the
      University of South Australia includes in its programs various opportunities for
      students to study abroad. It also encourages incoming short-term exchange and
      full-program international students. In 2001, the Discipline of Nursing and Rural
      Health (Whyalla Campus) sent two graduating students to a developing country in
      Asia, the Philippines, for a twelve-week academic experience. Despite problems
      causing the visit to be curtailed, much was learned. Participant and organiser
      insights are described, sharing valuable lessons to inform future plans and
      ensure better results. What could be regarded as a failed academic visit,
      nevertheless offered a life-changing opportunity and significant learning
      outcomes, reinforcing the belief that international academic experiences are
      extremely worthwhile for students and participating institutions. These
      experiences provide an important path to cultural understandings, and to personal
      and professional development.

PMID- 16646892
TI  - Interim leadership in an era of change.
AB  - As dean and chair positions in baccalaureate programs in nursing are vacated, the
      role of the interim leader can emerge as a confusing yet crucial role during the
      interregnum. This can occur even if the new administrator has had a faculty role
      at the institution. Without a comprehensive orientation or mentorship, the
      interim administrator may find the role perplexing and question which tactics
      they need to exercise to meet the expectations of the university, faculty, and
      stakeholders. The following article depicts a paradigm that the interim chair may
      employ to achieve the goals of the institution and department. An amalgamation of
      leadership theories and concepts create a framework for the interim leader to
      employ as the search for a permanent replacement ensues. The interim chair may be
      able to apply some of the relevant theories and discover that there are a
      plethora of resources within the nursing community to assist the individual in
      creating a positive impact within the academic setting.

PMID- 16646893
TI  - Developing nursing leaders through graduate education in Pakistan.
AB  - Advanced practice is the conceptual focus for the first Master's of Science in
      Nursing (MScN) program in Pakistan. Initiated at the Aga Khan University School
      of Nursing (AKUSON) in October 2001, this full time two-year program aims to
      prepare nurses who are leaders in nursing practice with advanced knowledge and
      skills for their roles in either urban, rural, tertiary-care or community
      settings. The significance of the progress must be emphasized in a country where
      most nursing education takes place at diploma level and relatively few
      opportunities exist for nurses seeking a baccalaureate degree. Other countries
      developing graduate nursing programs may benefit from the expereince in Pakistan.

PMID- 16646894
TI  - Planning for assessment of student learning outcomes: a process within your
      grasp.
AB  - Assessment in educational institutions is mandated by the public and by
      accrediting organizations. Faculty must plan for program assessment within the
      context of the college or university goals and assessment projects. Within the
      department or college of nursing, student learning outcomes must be assessed at
      the total program level and at the course and classroom levels. Faculty who are
      motivated to plan assessments and use outcome data should take leadership in the
      process. The process consists of determining the outcomes to be assessed, the
      measures to be used, and the standards to be reached. When data has been
      collected, it must be evaluated and used to make improvements. Finally, the
      assessment process itself should be assessed. This article gives examples of
      assessment methods for all levels of assessment at the institution, but
      especially at the program and course levels. A departmental assessment blueprint
      is included. The end result of implementation of an assessment plan is that at
      every level of the institution, excellence should be enhanced.

PMID- 16646895
TI  - Nursing students' perceptions of hospital learning environments--an Australian
      perspective.
AB  - Clinical education is a vital component in the curricula of pre-registration
      nursing courses and provides student nurses with the opportunity to combine
      cognitive, psychomotor, and affective skills. Various studies have suggested that
      not all practice settings are able to provide nursing students with a positive
      learning environment. In order to maximize nursing students' clinical learning
      outcomes, there is a need to examine the clinical learning environment. The
      purpose of this study was to assess pre-registration nursing students'
      perceptions of hospital learning environments during clinical field placement.
      Quantitative and qualitative methodology was used. One hundred and eight students
      provided quantitative data through completion of the survey instrument, the
      Clinical Learning Environment Inventory (Actual and Preferred forms). Each form
      is a 5-point Likert-type questionnaire, made up of 35 items consisted of 5 scales
      with 7 items per scale. Qualitative data, obtained through semi-structured
      interview of 21 students from the same cohort, were used to explain and support
      the quantitative findings. There were significant differences between students'
      actual and preferred perceptions of the clinical learning environments. Generally
      students preferred a more positive and favourable clinical environment than they
      perceived as being actually present. Since participants consisted of nursing
      students from just one university nursing school in South Australia, the findings
      may not be representative of all nursing students in general with respect to
      their clinical placement. However, the value of this study lies in the resulting
      implication for nursing education and future research. A better understanding of
      what constitutes quality clinical education from the students' perspective would
      be valuable in providing better educational experiences.

PMID- 16646896
TI  - Reflections on undergraduate nursing education: a look to the future.
AB  - The nursing shortage combined with a shortage of faculty have created new
      challenges for schools of nursing particularly at the undergraduate level. At a
      time when schools are attempting to increase student enrollment, there are fewer
      faculty available for teaching those students. Faculty are increasingly faced
      with more responsibilities and demands placed on them to prepare students with
      essential knowledge and skills for beginning practice. The purposes of this paper
      are to examine current challenges in undergraduate nursing education and some
      strategies for addressing them.

PMID- 16646897
TI  - Cultural competency education in American nursing programs and the approach of
      one school of nursing.
AB  - The importance of cultural competency in all areas of American society is well
      accepted. Indeed, the evolving demographics of the country make it imperative. A
      wide range of educational and work settings has addressed the concept, from
      business and government to education and health. Cultural competency is
      particularly critical in the realm of healthcare, as the potential impact on
      quality of health and life is at stake. Nursing is a leader in this field, with a
      long theoretical and practice history of attention to, and respect for,
      individual differences. This article reviews cultural competency education in
      nursing and its respective educational settings. Common threads and different
      models are discussed. The program components of cultural competency education in
      one School of Nursing are highlighted. Future directions towards refining
      cultural competency education are presented.

PMID- 16646898
TI  - A case study: the clinical application of quadrangular dialogue--a caring in
      nursing teaching model.
AB  - Teaching caring in nursing is expected of nursing faculty, but the practical
      application is rarely explained. It has been regarded as the moral responsibility
      of faculty to teach in a caring way. This case study relates how one faculty
      applied the concepts to quadrangular dialogue a caring model of nursing education
      to the experience of baccalaureate student nurses in their first clinical
      rotation. The components of quadrangular dialogue will be described, and applied
      to a specific patient who was cared for by students in one semester. This model
      is developed from Habermas' (1995) Theory of Communicative Action and Moral
      Consciousness, Bishop and Scudder's (1990) Triadic Dialogue and a caring in
      nursing paradigm developed by this author. It explains how the patient, nursing
      student and nursing faculty are all first person in the interaction, while the
      illness is object. By acknowledging the humanness of participants, validation and
      fulfillment for each follow.

PMID- 16646899
TI  - The tyranny of consensus: implications for nursing education.
AB  - The egalitarian appeal of decision making based on consensus has been valued as a
      strong alternative to other decision making approaches such as voting. In this
      paper, we identify some of the challenges inherent in this view, and suggest
      consideration of alternative decision making approaches needed at times to help
      nurse educators in their work with students and colleagues. As nurse educators,
      we have a responsibility to educate students about the meanings of consensus, to
      encourage open discussion about implicit values underlying behaviors, and help
      them appreciate the importance of dissent in a democratic society. Our challenge
      is to ensure that we are using, and teaching, the best decision making process
      for the circumstance.

PMID- 16646900
TI  - Exploring the attributes of critical thinking: a conceptual basis.
AB  - Many teaching methods used in nursing education to enhance critical thinking
      focus on teaching students how to directly apply knowledge; a technically
      rational approach. While seemingly effective at enhancing students' critical
      thinking abilities in structured learning situations, these methods don't prepare
      students to operationalize critical thinking to manage the complexities that
      actually exist in practice. The work of contemporary educational theorists Paulo
      Freire, Donald Schon, Chris Argyris, Jack Mezirow, Stephen Brookfield, and Robert
      Tennyson all share similar perspectives on thinking in practice and the use of
      reflection to achieve a coherence of understanding. Their perspectives provide
      insight on how educators can shift from a means-end approach to operationalizing
      thinking in practice. The author identifies four attributes of critical thinking
      in practice evidenced in these views, followed by a discussion of specific
      educational strategies that reflect these attributes, and operationalize a
      critical thinking process in nursing practice to achieve a coherence of
      understanding.

PMID- 16646902
TI  - Reader commends Banister and Schreiber, authors of the tyranny of consensus:
      implications for nursing education.

PMID- 16646903
TI  - Promoting clinical reasoning in undergraduate nursing students: application and
      evaluation of the Outcome Present State Test (OPT) model of clinical reasoning.
AB  - Promoting clinical reasoning in undergraduate nursing students through
      application of the Outcome Present State Test (OPT) Model of Clinical Reasoning,
      is a challenge that can be successfully managed through effective teaching
      learning strategies. Empirical evidence to support teaching strategies that
      foster both cognitive and metacognitive skill acquisition is limited. The purpose
      of this research was to evaluate the development of clinical reasoning skills
      among nursing students through the application and evaluation of teaching
      learning strategies associated with self-regulated learning and the OPT model
      (Pesut & Herman, 1998; 1999; Pesut, 2004). The model and self-regulated learning
      prompts were used to structure learning with junior level baccalaureate nursing
      students during a ten-week, medical-surgical clinical experience in acute care
      telemetry units. Data analysis revealed students effectively made gains in
      learning associated with the OPT model. Qualitative analysis of self-regulated
      learning prompt journal data revealed students made significant gains in self
      observation, self-judgment, knowledge work and use of health care personnel
      resources during clinical experiences. Results indicated the intentional use of
      guided reflection coupled with structure and learning tools of the OPT model
      significantly enhanced clinical reasoning skill acquisition, and provided
      evidence for the effectiveness of structured teaching learning strategies.

PMID- 16646904
TI  - PDAs bring information competence to the point-of-care.
AB  - The ability of nursing faculty and students to efficiently obtain accurate
      information at the point-of-care is a critical aspect of providing quality
      patient care. Personalized Digital Assistants (PDAs) can provide instant access
      to entire textbooks of information where it is needed most, in the dynamic
      learning environment of the clinical setting. With a growing trend in higher
      education to include instruction on information competency in the curriculum, the
      use of PDAs in nursing education needs to be explored. This article discusses the
      use of PDAs by faculty and students within one nursing program. Results from a
      survey of faculty and students demonstrated a clear discrepancy in their use of
      PDAs. Although students recognized the benefits of PDA use in the clinical
      setting, they did not want owning a PDA to be a program requirement. Discussed
      are several approaches being used to overcome identified barriers to PDA use and
      ownership.

PMID- 16646905
TI  - An inventory of nursing education research.
AB  - PURPOSE: To describe nursing education research literature in terms of quality,
      content areas under investigation, geographic location of the research, research
      designs utilized, sample sizes, instruments used to collect data, and funding
      sources. DESIGN AND METHODS: Quantitative and qualitative research literature
      published between January 1991 and December 2000 were identified and classified
      using an author-generated Relevance Tool. FINDINGS: 1286 articles were accepted
      and entered into the inventory, and an additional 22 were retained as references
      as they were either literature reviews or meta-analyses. Not surprisingly, 90% of
      nursing education research was generated in North America and Europe, the
      industrialised parts of the world. Of the total number of articles accepted into
      the inventory, 61% were quantitative research based. The bulk of the research was
      conducted within the confines of a course or within a program, with more than
      half based in educational settings. Sample sizes of the research conducted were
      diverse, with a bare majority using a sample between 50 and 99 participants. More
      than half of the studies used questionnaires to obtain data. Surprising, 80% of
      the research represented in these articles was not funded. The number of
      publications of nursing education research generated yearly stabilised at
      approximately 120 per year. CONCLUSION: Research programs on teaching and
      learning environments and practice in nursing education need to be developed.
      Lobbying is needed to increase funding for this type of research at national and
      international levels.

PMID- 16646906
TI  - Scholarly teaching and scholarship of teaching: noting the difference.
AB  - Scholarly teaching and the scholarship of teaching are being discussed more
      frequently in the nursing education literature, yet a clear distinction between
      the two is often not made. In this paper we will identify the differences between
      the two and the role each plays in faculty evaluation. We argue that all faculty
      members should be scholarly teachers but not all will or should engage in the
      scholarship of teaching.

PMID- 16646907
TI  - Recruitment and retention of minority students: diversity in nursing education.
AB  - A culturally diverse nursing workforce is essential to meet the health needs of
      an increasingly diverse Canadian population. The recruitment and retention of
      nursing students representing diverse backgrounds are vital to the building of
      this diversified work force. Studies have shown that diversity within the student
      body benefits everyone. For example, students who study and work within a diverse
      environment are better able to understand and consider multiple perspectives and
      to appreciate the benefits inherent in diversity. This paper describes one school
      of nursing's project on the Recruitment and Retention of Black students into
      their Bachelor of Science Nursing (BScN) Program. The project goals are to
      increase diversity, foster student learning, and ultimately improve health care
      for the Black community. Presented in this paper are the project background,
      implementation process, challenges and outcomes. This may provide learned lessons
      and future directions for similar initiatives in other institutions.

PMID- 16646908
TI  - Helping baccalaureate nursing students care for the wellbeing of older adults.
AB  - Because the world's population is aging there is a dire need for gerontologically
      prepared registered nurses. Baccalaureate nursing students, therefore, need
      experiences with older adults. However, due to constraints on their practice,
      students might have insufficient opportunities to learn about how to contribute
      to older adults' wellbeing. Students provided with a combination of learning
      experiences may understand how to contest constraints on their practice and
      create conditions that facilitate the provision of age-responsive care for older
      adults. In this paper gerontological-nursing content, constraints on practice,
      and learning experiences to help students come to understand their contributions
      to older adults' wellbeing are identified. Potential benefits of these learning
      experiences for students, older adults, and the nursing profession are discussed.

PMID- 16646909
TI  - "Surviving": registered nurses' experiences in a baccalaureate nursing program.
AB  - In 2000, one Canadian university began offering a 12-month baccalaureate program
      to provide registered nurses (RNs) with a condensed program to expedite
      baccalaureate preparation. The paucity of current literature regarding returning
      RNs' experiences emphasized the need to explore these students' perceptions
      regarding their educational experiences. Twelve participants were interviewed for
      this descriptive/exploratory study. A major theme of "surviving" emerged from the
      qualitative analysis. Surviving embraced the themes of "the quest", "the
      struggle", and "the aftermath". Implications for nursing curriculum and program
      development and recommendations for research are discussed.

PMID- 16646910
TI  - Addressing complex health issues: developing contextual knowing through sequenced
      writing and presentations.
AB  - When students discuss possible solutions for health problems they tend to form
      quick opinions, rush to conclusions, and suggest answers that do not address all
      the factors or stakeholders involved. Therefore, teaching the complexity of
      community health issues can be challenging. A series of learning activities
      applying Baxter-Magolda's model of four stages of college students' intellectual
      development is used to help students address complex health problems. Two written
      assignments and two presentations involving role playing are sequenced throughout
      the semester. This project has been well received by students and other faculty.

PMID- 16646911
TI  - Learning from experience: three community health population-based outreach
      projects for graduate and undergraduate students.
AB  - Three outreach activities by a school of nursing, in partnership with community
      agencies, provided learning experiences in primary and secondary preventive
      health care for graduate and undergraduate nursing students while addressing
      health needs in the community. The activities included administration of
      immunizations to a newly arrived Somali Bantu refugee population, targeted
      screening of an African-American population at risk for diabetic retinopathy, and
      general health screening for an underserved Hispanic immigrant population. These
      activities lend insight and depth to a community health curriculum by allowing
      students to provide needed services while engaging with culturally diverse
      clients of varying socioeconomic status. Learner objectives, resources, processes
      and outcomes are provided for each example.

PMID- 16646912
TI  - Challenges and opportunities of international clinical practica.
AB  - International clinical practica are a strategy to integrate a global dimension in
      nursing curricula and achieve culturally sensitive nursing practice. In this
      paper, a review of the history and development of international practica for
      nursing students is presented, and research evaluating the effectiveness and
      impact of international experiences is analyzed. A description of experiences
      working with Canadian nursing students is used to highlight the challenges and
      opportunities inherent to international clinical practica. International student
      experiences involving clinical practica pose challenges that are additional to,
      and often more complex than, those faced in traditional international, course
      based exchanges. The significant opportunities, however, continue to make
      international student practica a desirable and positive experience for Canadian
      nursing students.

PMID- 16646913
TI  - Graduate students' perceptions of the practice of posting scholarly work to an
      online class forum: balancing the rhetorical triangle.
AB  - In both healthcare and education, basing one's practice upon research evidence,
      has become very important. This paper presents the findings from a descriptive
      analysis of graduate students' perceptions of the practice of posting their
      scholarly work to a class discussion forum, where it can be read by their peers.
      The resulting themes are described and discussed in relation to the balance of a
      model of rhetorical stance or a rhetorical triangle. This will be of interest to
      instructors facilitating courses with online capacity.

PMID- 16646914
TI  - Transforming nursing education: a partnership social system for alignment with
      philosophies of care.
AB  - It has been made clear by nurse educators and theorists such as Bevis (1989),
      Benner, Tanner, and Chesla (1996), and Bevis and Watson (2000) that a movement
      away from the traditional, behavioral, medical-model of lecture and behaviorism
      as the main modalities for teaching and learning in nursing is essential. Why is
      it then that nursing education by and large is still taught via lecture and
      behavioralist methodologies (Bevis & Watson, 2000), despite the proliferation of
      research related to innovations in nursing education? This paper examines the
      parallel between the prevailing Western "dominator" social system or paradigm,
      "masculine" values/ traits, and the established behavioralist-medical methodology
      of teaching nursing. How nursing education in general has been influenced by the
      dominator social system is discussed and an argument for why nurse educators
      might consider working towards more effective means of closing the gap between
      caring-humanistic nursing philosophies and actual educational practices
      presented.

PMID- 16646915
TI  - Educating nurses for the knowledge economy.
AB  - When discussing the education of nurses for the knowledge economy it must be
      assumed that nursing is influenced by multiple factors reflective of the broader
      society in which it exists. These factors include civil society, social justice,
      and the public sector, all of which converge to shape nursing education and
      ultimately nursing practice. Over the past decade in particular, these factors
      have been greatly affected by what may be described as the hegemonic influences
      of the knowledge economy and the philosophical assumptions on which it is based,
      influences that are impacting directly on how the health system is evolving. The
      author posits, therefore, that it is incumbent on faculty to educate future
      nurses for the knowledge economy and to provide them with appropriate tools with
      which to meet the many challenges that confront them today and will invariably
      continue to confront them in the coming decades.

PMID- 16646916
TI  - The process of Master's education in nursing: evolution or revolution?
AB  - In this qualitative, descriptive study, the process of achieving change in
      knowledge and attitudes through Master's education in nursing is examined. Twenty
      two recent graduates from three Ontario universities participated in semi
      structured, taped interviews. Participants recounted personal and professional
      changes they attributed to completing a Master's program in Nursing and their
      experience of the process of change. After responding to questions about
      differences they perceived in themselves, participants reviewed Mezirow's (1991;
      1994) 11 stages of perspective transformation and discussed whether these phases
      resonated for them. Some felt that the stages described their experience
      accurately; others reported their experience of the process was not as dramatic
      as Mezirow's description implied. Several who had taken degree completion
      baccalaureate programs perceived their baccalaureate experience to be more
      congruent with Mezirow's transformation process than the change process in their
      Master's program. At the Master's level, the majority felt the changes were
      evolutionary, not revolutionary. Most reported that rather than undergoing a
      perspective transformation, they were building on values and attitudes from the
      baccalaureate level. This study contributes to understanding the processes of
      change experienced by students in graduate education in nursing.

PMID- 16646917
TI  - Goal orientation and its relationship to academic success in a laptop-based BScN
      program.
AB  - This longitudinal study, conducted within a laptop-based BScN program examines
      the relationship of goal orientation profiles to comfort with technology and
      academic success. In phase 1 of this study, 101 first year nursing students
      completed an on line survey. The measurement tools used were Goal Orientation
      Assessment, Multiple Intelligences Learning Inventory and a locally developed
      Technology Comfort survey. Results showed that students were predominantly high
      in the mastery goal orientation profile. Males had a higher comfort level with
      technology. Age was inversely related to comfort with technology. An unexpected
      finding was that grade point average was inversely related to comfort with use of
      technology. The data did not support the commonly held belief that today's
      students are uniformly well-skilled and comfortable with new technologies. This
      study will continue over the next three years and will allow comparison of
      variables over time. Specific teaching interventions may be developed to
      accommodate varying learning and motivational styles in relation to comfort with
      technology.

PMID- 16646918
TI  - Enriching clinical learning experiences in community health nursing through the
      use of discussion boards.
AB  - The purpose of this article is to describe how a constructivist approach to
      learning, using an internet-based discussion board, can be used to support the
      reflection and dialogue of registered nurse students in a community health course
      in an accelerated RN-to-BS program. The constructivist structure of the course is
      described and insights from students shared, revealing learning in the areas of
      critical reflection, professional growth, and peer support. Suggestions for
      implementation of the educational strategy are provided.

PMID- 16646919
TI  - Perspectives of Latin American nursing professors and leaders about research
      competencies needed by nurses with different levels of academic preparation.
AB  - This article describes a study to identify perspectives of Latin American nursing
      professors and leaders about the research competencies needed by students with
      different levels of academic preparation (bachelor's, master's, and doctoral).
      The sample included 42 nurses from eight Latin American countries who wrote
      narrative comments on a questionnaire sent by e-mail. The responses were analyzed
      by a process of content analysis. The participants identified differences that
      should be emphasized in the different academic levels. The findings could be used
      to develop educational programs to prepare nurse researchers.

PMID- 16646920
TI  - Depression, stress, emotional support, and self-esteem among baccalaureate
      nursing students in Thailand.
AB  - Nursing students are valuable human resources. Detection of potential depression
      among nursing students is crucial since depression can lead to low productivity,
      minimized quality of life, and suicidal ideas. Identifying factors affecting
      depression among students can help nursing educators to find ways to decrease
      depression. The purpose of this study was to examine rates of depression and the
      associations between depression and stress, emotional support, and self-esteem
      among baccalaureate nursing students in Thailand. This correlational, cross
      sectional study recruited 331 baccalaureate Thai nursing students. Students
      completed three instruments that had been translated into Thai: The Center for
      Epidemiology Studies Depression Scale, Perceived Stress Questionnaire, and
      Rosenberg Self-Esteem Scale. Another instrument created in Thai was used to
      measure emotional support. Results revealed that, when using the standard
      definition, 50.1% of the students were depressed. Stress was positively related
      to depression, whereas emotional support and self-esteem were negatively related
      to depression.

PMID- 16646921
TI  - A tri-level HIV-prevention educational intervention.
AB  - Preventing HIV transmission is a major world health goal. The international
      nursing shortage and the cost of educational and healthcare require innovative
      approaches to meet this goal. The initiative described provided HIV education at
      three levels: to students in an R.N. to BSN program, lay health advisors (LHA's),
      and participants in a high-risk community. Students completed the traditional
      community needs assessment and teaching plans. Additionally, they contributed to
      funding proposals, implemented and evaluated their plan. They prepared LHA's as
      peer group educators. This was cost-effective and increased credibility in an
      African-American community. Using tested materials tailored to this population,
      six LHA's conducted 24 sessions in two months. Of the 168 community participants,
      151 completed the pre-and post-test of HIV knowledge. Correct responses increased
      significantly overall from 81.9% to 88.3 (t = 4.88, df = 150; p = .001). The
      three items with the greatest change in correct responses related to African
      American HIV exposure, female condoms, and lubricants. Rationale for the project
      and recommendations for improvement are included.

PMID- 16646922
TI  - The strength of rural nursing: implications for undergraduate nursing education.
AB  - Nursing in rural communities offers opportunities for independent nursing
      practice and community participation. However, recruitment of nurses to rural
      settings can be difficult. In response to this challenge and the rising demand
      within nursing education for community clinical placements, intensive, short
      term, rural community clinical placements are being developed by urban
      universities. As yet, little research has examined the use of these placements
      for undergraduate nursing education. The purpose of this qualitative research
      study was to examine the experiences of students, registered nurse mentors, and
      clinical instructors in rural health clinical placements, as part of a larger
      study examining alternative clinical placements. Through use of the interpretive
      descriptive method, the perspectives of participants were elicited from focus
      groups and interviews. The paradox of nursing student placements in rural health
      is that limitations of the rural site became the impetus for nursing student
      learning and partnership. An implication is that service learning partnerships be
      pursued for mutual benefit of students, communities, and rural nurses.

PMID- 16646923
TI  - Narratives of social justice: learning in innovative clinical settings.
AB  - The nursing profession has renewed its commitment to social and political
      mandates, resulting in increasing attention to issues pertaining to diversity,
      vulnerable populations, social determinants of health, advocacy and activism, and
      social justice in nursing curricula. Narratives from a qualitative study
      examining undergraduate nursing student learning in five innovative clinical
      settings (corrections, international, parish, rural, and aboriginal) resonate
      with these curricular emphases. Data were derived from focus groups and
      interviews with 65 undergraduate nursing students, clinical instructors, and RN
      mentors. Findings of this study reveal how students in innovative clinical
      placements bear witness to poverty, inequities, and marginalization (critical
      awareness), often resulting in dissonance and soul-searching (critical
      engagement), and a renewed commitment to social transformation (social change).
      These findings suggest the potential for transformative learning in these
      settings.

PMID- 16646924
TI  - Web-enhanced and face-to-face classroom instructional methods: effects on course
      outcomes and student satisfaction.
AB  - Web-enhanced courses are increasingly popular for providing rich learning
      experiences and greater flexibility in achieving course outcomes. As technology
      emerges as an adjunct to face-to-face teaching methodologies, nursing educators
      are compelled to determine to what extent students are able to meet course
      objectives when technology is used to enhance the classroom experience. Graduate
      nursing students enrolled in face-to-face and web-enhanced sections of a course
      were evaluated on technical ability, learning style, learning outcomes, and
      course satisfaction. There was no difference on technical ability and learning
      outcomes. Overall, students in the web-enhanced section were more satisfied with
      the course, and reported advantages such as greater flexibility in scheduling,
      less travel, and greater independence and self-pacing of content. The data
      suggest that web-enhanced courses can provide a valid alternative to more
      traditional face-to-face classroom formats, and may remove some of the barriers
      to pursuing advanced nursing degrees.

PMID- 16646925
TI  - Is plagiarism creating an opportunity for the development of new assessment
      strategies?
AB  - Have traditional student assessment strategies such as the formal written paper
      outlived their usefulness? Given reports of plagiarism in post-secondary
      institutions and the ease with which students can 'cut and paste' content from
      online sources, the relevance and applicability of traditional assessment
      strategies need to be examined in light of these technological advances. The
      introduction of technology and the Internet into classrooms has been the most
      important educational change to occur in the last one hundred years, yet
      assessment strategies reflect the characteristics of the printing press to a
      greater extent than the capabilities of technology and the Internet. The paper
      explores a connection to the visual arts in terms of creation, re-creation, the
      'desire to conceal', and contemporary means of interpretation. A search of the
      literature reveals a need for teaching and learning environments to evolve along
      with a technologically-based society.

PMID- 16646926
TI  - Evaluation of a clinical teaching method involving stories.
AB  - A clinical teaching method involving stories was evaluated in this study. A total
      of 25 ASN and BSN students participated in Phase I evaluation and another 16 ASN
      students were included in Phase II. Each student created a story about an
      obstetric or a pediatric topic. The story was then read by the story writer to
      peers and faculty. The faculty member facilitated dialogues and reflections on
      the meanings of the story. In Phase I, students offered written responses about
      the effectiveness of the story teaching. In Phase II, a 5-item questionnaire
      measured pre- and post-test scores of perceived improvement in five knowledge
      areas. Results showed that students perceived the story teaching positively
      because it brought learning to a personal level and facilitated in-depth
      discussion and critical thinking. Perceived knowledge improvement was evident
      after the story teaching in nursing interventions, the physiological and
      psychosocial alterations, legal/ethical/cultural issues, and community resources.
      In conclusion, this teaching method was acceptable to students and may have
      contributed to positive learning outcomes.

PMID- 16646927
TI  - Using education to promote research dissemination in nursing.
AB  - In order to maintain the highest standards of care, nurses need to be aware of
      the most recent and relevant research and use this to inform their practice.
      However, this is often difficult because of both the limited time available in
      which to access research and the need for advanced critical appraisal skills.
      Further, given the overload of complex research information, nurses may be
      overwhelmed by the extent of available research. This paper describes a unique
      approach, the Web Resource Appraisal Process (WRAP), for integrating research and
      education by directly engaging nurses undertaking postgraduate studies in the
      review of existing research as it is applied to the contemporary workplace. In so
      doing, experienced nurses investigate the application of research to practice by
      actively engaging in research dissemination, communication, and education. By
      engaging in this process, nurses generate new knowledge based on the integration
      of current research with their practice experience, while simultaneously gaining
      the benefits of experiential learning.

PMID- 16646928
TI  - Perspectives of nursing education in Poland.
AB  - Nursing education in Poland are developing slowly but steadily in response to
      changing social needs and emerging healthcare issues. In particular, the
      immediate demand for more nurses is generating innovation in nursing education
      and encouraging Polish universities to graduate more nurses. Unfortunately,
      nursing wages remain low in regards to other professions, which only fuels the
      nursing shortage. Polish nurses are also facing staffing issues. At times, the
      nurse-patient ratio is 28 to 1. These working conditions also discourage people
      from pursuing a career in nursing. Finally, male nurses are rare in Poland. The
      future of nursing in Poland will be dictated by the Polish government and
      university systems and their efforts to produce more graduate nurses who can
      thrive and practice in a more complex, evolving world and who receive competitive
      pay for their expertise.

PMID- 16646929
TI  - Teaching nursing students to assess and intervene for domestic violence.
AB  - Domestic violence is recognized as a priority women's health issue. Despite its
      prevalence, the majority of accredited nursing schools in the United States has
      yet to adequately integrate violence assessment and intervention content and
      planned clinical experiences into their curriculum. Therefore, the author has
      developed a theoretically based one-day domestic violence immersion activity to
      enhance the teaching of domestic violence assessment and intervention skills to
      baccalaureate nursing students.

PMID- 16646930
TI  - Strengthening workforce relationships: developing practice learning.
AB  - A joint partnership between a University and its local hospitals developed and
      implemented Practice Learning Teams (PLTs) to enhance student nurse learning
      experiences. In order to achieve this, PLTs arrived at clear aims and purposes,
      with educators and nurses working collaboratively and being jointly responsible
      for the quality of students' placement experience. This study occurred after a
      year of implementation, and a range of stakeholders were interviewed in order to
      evaluate perceived effectiveness. Findings of this report suggest the majority of
      respondents thought PLTs should be retained, recognising that they were new, and
      thus required development. There was a clear difference between effective and
      ineffective PLTs. Effective teams were considered to support the students'
      practice-based learning and mentors, while providing a forum for sharing 'good
      practice', discussion and problem solving. Less effective teams were
      characterised by having a low attendance or a membership that lacked enthusiasm
      and/or willingness to participate.

PMID- 16646931
TI  - Implementing and evaluating a culturally-focused curriculum in a collaborative
      graduate nursing program.
AB  - For more than a decade, nurses and nurse educators have been held to national and
      professional goals aimed at affirming diversity, integrating cultural competence,
      and closing the healthcare disparity gap. Faced with shrinking resources, meeting
      these goals has been harder to achieve. In September 2004, the Sullivan
      Commission report renewed attention to the widening gap in healthcare quality for
      America's growing minority population as well as the shortage of minority
      healthcare providers. The focus of this article is how faculty at a collaborative
      nurse practitioner program responded to these concerns. Described is a
      multifaceted approach, beginning with participation in a nationally recognized
      cultural awareness workshop and continuing through a process designed to bridge
      theory with clinical and classroom practice. Emphasis is given to the challenges
      of meeting the needs of a wide geographic area and the opportunities engendered
      by shared resources.

PMID- 16646932
TI  - Journaling; an active learning technique.
AB  - Journaling is a method frequently discussed in nursing literature and educational
      literature as an active learning technique that is meant to enhance reflective
      practice. Reflective practice is a means of self-examination that involves
      looking back over what has happened in practice in an effort to improve, or
      encourage professional growth. Some of the benefits of reflective practice
      include discovering meaning, making connections between experiences and the
      classroom, instilling values of the profession, gaining the perspective of
      others, reflection on professional roles, and development of critical thinking. A
      review of theory and research is discussed, as well as suggestions for
      implementation of journaling into coursework.

PMID- 16646933
TI  - Post-master's certificate in nursing education.
AB  - With the continued shortage of nursing faculty, schools of nursing need short yet
      effective means of preparing educators to teach in their programs. One such
      strategy is a post-master's certificate in nursing education. This article
      describes the courses, learning activities, and outcomes of a post-master's
      certificate program in nursing education. Twenty-five graduates, randomly
      selected from the 53 who had completed the program, were interviewed. The
      findings indicated that a post-master's certificate was an effective strategy for
      preparing nurse educators and meeting the demands for more faculty in a short
      period of time.

PMID- 16646934
TI  - Validation of the clinical learning environment and supervision scale.
AB  - The aim of the study was to validate a new research instrument to evaluate the
      quality of the clinical learning environment and the supervision given to nursing
      students by qualified staff nurses. This paper describes the validation process
      of the research instrument. Dunn's and Burnett's (1995) CLE scale was chosen for
      the concurrent research instrument to test validity. The theoretical framework of
      this study draws on empirical research into clinical learning environments and
      supervision undertaken during the 1980's and 1990's. The sample consisted of
      nursing students who had undertaken a clinical placement in a hospital setting.
      The data (n=416) were collected from four Nursing Colleges in Finland. Students
      evaluated their clinical placements as being 'good' in both instruments. The
      supervisory relationship was the most important factor in students' supervisory
      system but this requires a positive atmosphere and a 'good' leadership in order
      to be effective. The congruence between the instruments in use was high so that
      it is impossible to note the possible impact of cultural differences in this
      instrument validation process.

PMID- 16646935
TI  - Extending the evidence base for nursing education.

PMID- 16646936
TI  - Preceptor selection, orientation, and evaluation in baccalaureate nursing
      education.
AB  - The benefits obtained from properly managed clinical preceptorships cannot be
      underestimated. Nursing students benefit from clinical preceptors who exemplify
      the application of theoretical knowledge in actual clinical settings.
      Preceptorships, and the use of preceptors, remain a viable and important adjunct
      for faculty in US schools of nursing. This article reports on a portion of a
      study of undergraduate baccalaureate nursing programs and the use, selection, and
      evaluation of clinical preceptors. The results suggest that the design of most
      preceptorship programs does not consistently secure the use of qualified clinical
      preceptors. Today's clinical preceptors need to be more carefully selected,
      oriented, and evaluated to ensure quality education of nursing students. Benefits
      can be realized not only in nursing education, but also in nursing practice,
      patient care, and nursing administration. More research needs to be done in the
      area of clinical preceptorships and more specifically, selection and evaluation
      methods.

PMID- 16646937
TI  - Selecting and applying taxonomies for learning outcomes: a nursing example.
AB  - In this manuscript procedures for selecting and applying taxonomies using nursing
      related examples are described. Bloom's taxonomy and Gagne's instructional theory
      are compared. The author concludes that both taxonomies have much in common and
      are appropriate for use in nursing education.

PMID- 16646938
TI  - Action methods in the classroom: creative strategies for nursing education.
AB  - Nursing education recognizes the need for a framework of experiential learning
      that supports the development of professional roles. Action methods, originated
      by Jacob L. Moreno (1953), can be readily adapted to any nursing classroom to
      create the conditions under which students learn and practice professional
      nursing roles. While nurse faculty can learn to use action methods, they may not
      fully comprehend their theoretical underpinnings or may believe they are only
      used in therapy. This article explores Moreno's ideas related to psychodrama and
      sociodrama applied in classroom settings, and presents many examples and tips for
      classroom teachers who wish to incorporate action methods into their classes.

PMID- 16646939
TI  - Integrating clinical guidelines into nursing education.
AB  - A project planning group consisting of college and university representatives
      from a collaborative undergraduate nursing program developed an inclusive,
      process-oriented faculty development initiative to enhance the integration of
      clinical guidelines in clinical courses. In the first phase, results of a needs
      assessment were used to inform the development of a six-hour workshop for the
      third year clinical faculty in acute care, mental health, and community health.
      Pre-post surveys were conducted with students and clinical faculty during the
      first phase. Results from the workshop and surveys were used to develop a four
      hour workshop for clinical faculty in all years of the program. The relatively
      short workshop process shows promise for initiating integration of clinical
      guidelines in undergraduate nursing education.

PMID- 16646940
TI  - Educating the future eHealth professional nurse.
AB  - Nursing is at the cusp of a truly revolutionary time in its history with the
      emergence of electronic health (eHealth) technologies to support client care.
      However, technology itself will not transform healthcare without skilled
      practitioners who have the informatics background to practice in this new
      paradigm of client care. Nurse educators have been slow to react to the matter of
      the necessary knowledge, skills, and practice competencies required for nurses to
      function as eHealth practitioners. Specifically, undergraduate nursing education
      must take a proactive stance towards curriculum development in the areas of
      eHealth and informatics. The purpose of this paper, therefore, is to propose
      recommendations about the review and redesign of nursing curricula in relation to
      nursing informatics. Recommendations include increased information literacy
      education, interdisciplinary collaboration, and client-centred technologies.
      Recommendations for faculty development in nursing informatics are also provided.

PMID- 16646941
TI  - Engaging baccalaureate clinical faculty.
AB  - Role theory was utilized in this descriptive study to investigate clinical
      faculty in baccalaureate nursing programs. The Clinical Faculty Role
      Questionnaire was developed and employed to study 134 full-time and part-time
      clinical faculty members. Theory derivation was used and the concept of role
      engagement was empirically supported. Pearson's correlation analysis was used to
      investigate the relationships among the variables. T-test results identified
      differences between full-time and part-time faculty members on role variables of
      status, role conception, and role engagement. The relationships between study
      concepts and areas of educational content related to the teaching role were
      explored and identified as supportive of the clinical educator role. Ancillary
      qualitative investigation resulted in the identification of several themes: the
      need for clinical competence; for part-time faculty, a desire to be included in
      program planning.

PMID- 16646942
TI  - Nursing EDGE: evaluating delegation guidelines in education.
AB  - Delegation, an important concept for nursing students to learn and practice, is
      central to registered nurse (RN) performance, and important on the NCLEX-RN
      examination. Nursing faculty members from an ADN program designed a descriptive
      study to evaluate planned versus actual delegation in the curriculum, and a
      second study to evaluate an intervention on delegation. Study One assessed the
      presence of delegation in each nursing course. Statistical analysis compared the
      planned implementation with the results for student definitions of delegation,
      and identification of the five rights of delegation based on the National Council
      of State Boards of Nursing (NCSBN) definition and five rights. Study one results
      are shared. Study Two utilized a comparison of pre-to-post intervention measures.
      Students were asked to complete eight steps of a delegation exercise and
      determine what could be delegated to an unlicensed assistant, and what should be
      completed by the RN. Answers were coded and entered into SPSS. Statistical
      analysis compared each student's ability to correctly identify the five rights of
      delegation prior to the exercise, against the ability to correctly answer five
      questions two weeks post exercise. Significant improvement (p< 0.05) occurred on
      each measure. Recommendations are discussed.

PMID- 16646943
TI  - Malaysian registered nurses' professional learning.
AB  - Findings of a study of the impact of professional learning on Malaysian
      registered nurses are reported. The offshore delivery post-registration nursing
      degree programme is a formal aspect of professional learning, which enables
      Malaysian registered nurses to upgrade their hospital-based training or diploma
      of nursing qualification to a degree. Using a qualitative case study approach,
      data were collected from twelve programme graduates, through individual and focus
      group interviews. The programme promoted their personal professional growth and
      enhanced their professional development. It increased self-confidence, knowledge,
      self-fulfillment, critical thinking ability, interpersonal skills, interest in
      research and research utilisation, and life-long learning. There was evidence of
      career mobility and a raised awareness of their professional role and
      responsibility.

PMID- 16646944
TI  - Contextual learning: a reflective learning intervention for nursing education.
AB  - Nursing educators need to continue to explore ways that new pedagogies such as
      narrative pedagogy and reflective practice inform and extend students' thinking
      in classroom and clinical situations. The goal of instruction becomes creating an
      opportunity for learning that integrates content knowledge with knowledge of the
      context. Educational methodologies that incorporate the use of context in a
      reflective, dialogical approach over time hold much promise in developing a
      dynamic process of thinking in practice. Contextual learning is a reflective
      learning intervention that offers new possibilities for nurse educators to
      prepare nurses to think critically in practice. In this expository paper the
      design and instructional methodology of contextual learning is discussed,
      beginning with a brief overview of the nature of critical thinking and the use of
      narrative as major underpinnings in the development of this intervention.
      Examples of how the intervention was implemented with novice nurses in practice
      is provided. Finally, reflections on how the intervention could be refined for
      nursing students is offered.

PMID- 16646945
TI  - Teaching through storytelling: an exemplar.
AB  - Many new faculty are being hired to fill the ever-increasing vacancies created by
      the attrition of current faculty members. To meet the diverse demands of today's
      educational climate, new faculty must develop an understanding of a variety of
      learning environments and skill in traditional and contemporary teaching
      strategies. This article presents storytelling as one strategy for educating
      potential new faculty in online instruction in an undergraduate nursing research
      course.

PMID- 16646946
TI  - Influence of nurse characteristics on the acquisition of cultural competence.
AB  - This study examined how nurses' personal and professional characteristics
      influenced their response to an educational intervention to improve their
      cultural knowledge and cultural competence. A one-group repeated measures design
      was used to evaluate the effectiveness of the intervention, which 76 public
      health nurses (PHNs) attended. Regression analysis showed that nurses with fewer
      years of nursing experience and higher level of education had a weak association
      with increased cultural knowledge and cultural competence but learning style and
      age were not associated with the outcomes.

PMID- 16646947
TI  - Using imaginative literature to foster cultural sensitivity.
AB  - Readings from two novels, Sandra Cisneros' The House on Mango Street and Toni
      Morrison's The Bluest Eye, were included in maternal-child clinical courses as
      part of a pilot project to identify potentially effective strategies for
      increasing student cultural sensitivity and reflective thinking skills. The
      authors analyzed student journals to determine student values and beliefs during
      maternal-child clinical experiences. The study sample consisted of 40 young women
      enrolled in a baccalaureate nursing program in a private, liberal arts
      university. These young women consistently interpreted ;the other' in their own
      image. They responded most strongly to themes of belonging, including the
      struggles of immigrants to ;fit in,' the ways of being acceptable and valued in
      U.S. society, and the process through which students as nurses learn to accept
      and care for others who are different.

PMID- 16646948
TI  - Solution focused teaching: a transformative approach to teaching nursing.
AB  - Nurses work in complex health care systems, which today are based not only on
      medical treatment and cure, but also on enabling individuals and strengthening
      communities. This paper describes a curriculum approach to teaching nursing in an
      Australian university which seeks to prepare students for this environment.
      Underpinned by transformative education principles, and termed Solution Focused
      Nursing, specific teaching and learning strategies are discussed. A goal is to
      cultivate critical thinkers and knowledge workers, that is, nurses who are not
      only able to work skillfully, strategically, and respectfully with clients, but
      who also demonstrate discernment, optimism, and vision about nursing and health
      care.

PMID- 16646949
TI  - Conflict in the preceptorship or field experience: a rippling tide of silence.
AB  - A major component of the educative process in the professional disciplines is the
      field education/preceptorship experience in which students are afforded
      opportunities to develop professional competence under the tutelage of a
      practising professional and/or a university instructor. During this time students
      are exposed to competing discourses about what it means to think and act as
      nurses, teachers, doctors and social workers. Frequently, field teaching is
      characterized by conflictual situations involving students, field instructors and
      university faculty. Such conflict is poorly understood as indicated by the lack
      of literature available in the professional disciplines. The purpose of this
      study was to explore the phenomenon of conflict within the context of field
      teaching in professional education. Pivotal to this study was the issue of making
      sense of the conflict that prospective nurses, teachers, social workers and
      doctors experience in professional education within the practice realm and how
      such discourses shape their professional identities, practices and ultimate
      social values. At issue is the social construction of meaning that takes place
      within professional education. This study was conducted from the perspective of
      four professional programs including education, medicine, nursing and social
      work. The researchers focused on the final year of each program at a time when
      students were engaged in a major field/preceptorship experience in hospitals,
      schools, communities and social agencies. The experiences derived from the
      nursing data are presented in this paper.

PMID- 16646950
TI  - Connecting: perceptions of becoming a faculty mentor.
AB  - The school of nursing faculty at a liberal arts university created an innovative
      group-mentoring course to support students' progression through the undergraduate
      nursing program. The foundation of the mentoring program is the dynamic
      relationship between novice and expert. Students are enrolled in this one-hour
      course for each of their four semesters in the upper division nursing curriculum.
      Group membership (faculty and students) is consistent throughout this time. The
      mentoring course requires faculty to lead a process-oriented group. Faculty are
      confident in teaching courses that are content-driven but have struggled with the
      unstructured nature of facilitating a process-oriented group. Therefore, the role
      of group mentor has been identified by faculty as very challenging.The purpose of
      this study was to explore faculty members' perceptions of assuming the role of a
      group mentor. Eight subjects participated in audio-taped interviews guided by
      open-ended questions. Four themes emerged including uncertainty, evolution,
      mutuality, and milieu.

PMID- 16646951
TI  - Levels and predictors of knowledge and attitudes regarding pain among Israeli
      baccalaureate nursing students and nurses pursuing specialty certification.
AB  - This paper presents the research conducted in 2003 by the Nursing Division of the
      Israeli Ministry of Health regarding the level of and predictors of pain
      knowledge and attitudes of Israeli nursing students and certifying nurses, in the
      context of the Division's educational policy. Cross-sectional descriptive in
      design, the research included first and fourth year baccalaureate students and
      nurses beginning and completing certification programs (N = 1149). Knowledge and
      attitudes, educational level, experience and success in pain care were examined
      via a questionnaire based on the McCaffery and Ferrell and Riddell and Fitche
      tools. Student's t-test, Pearson correlations and ANOVA were used for data
      analysis. Educational level was the strongest predictor of knowledge and
      attitudes among nursing students and certifying nurses, contributing most of the
      42.8% explained variance. Small significant contributions were made by other
      variables. This indicates that formal education is a good vehicle for enhancing
      knowledge and attitudes.

PMID- 16646952
TI  - Development and psychometric evaluation of the eldercare cultural self-efficacy
      scale.
AB  - The purpose of this study was to describe the development and psychometric
      evaluation of the Eldercare Cultural Self-Efficacy Scale (ECSES). Bandura's
      Theory of Self-Efficacy provided the theoretical framework. The sample consisted
      of students (N=248) from seven schools of nursing in a northeast state. The
      psychometric evaluation included: item analysis, principal factor analysis (PFA)
      with orthogonal rotation, and internal consistency reliability using Cronbach's
      alpha. Descriptive statistics were used to determine levels of eldercare cultural
      self-efficacy among the sample. The PFA revealed a four factor structure
      (Assessing for Lifestyle and Social Patterns, Determining Cultural Health
      Practices, Determining Cultural Beliefs, and Dealing with Grief and the Losses
      Associated with Aging) that accounted for 61% of explained variance. The
      subscales alpha coefficients ranged from .82 to .95. Findings demonstrate the 28
      item scale to be a reliable and valid instrument for use in nursing education to
      examine students' confidence in caring for ethnically diverse elders.

PMID- 16646953
TI  - Forces of magnetism for nursing education.

PMID- 16646954
TI  - Structural dissection of the reaction mechanism of cellobiose phosphorylase.
AB  - Cellobiose phosphorylase, a member of the glycoside hydrolase family 94,
      catalyses the reversible phosphorolysis of cellobiose into alpha-D-glucose 1
      phosphate and D-glucose with inversion of the anomeric configuration. The
      substrate specificity and reaction mechanism of cellobiose phosphorylase from
      Cellvibrio gilvus have been investigated in detail. We have determined the
      crystal structure of the glucose-sulphate and glucose-phosphate complexes of this
      enzyme at a maximal resolution of 2.0 A (1 A=0.1 nm). The phosphate ion is
      strongly held through several hydrogen bonds, and the configuration appears to be
      suitable for direct nucleophilic attack to an anomeric centre. Structural
      features around the sugar-donor and sugar-acceptor sites were consistent with the
      results of extensive kinetic studies. When we compared this structure with that
      of homologous chitobiose phosphorylase, we identified key residues for substrate
      discrimination between glucose and N-acetylglucosamine in both the sugar-donor
      and sugar-acceptor sites. We found that the active site pocket of cellobiose
      phosphorylase was covered by an additional loop, indicating that some
      conformational change is required upon substrate binding. Information on the
      three-dimensional structure of cellobiose phosphorylase will facilitate
      engineering of this enzyme, the application of which to practical oligosaccharide
      synthesis has already been established.

PMID- 16646955
TI  - Identification of a PDZ protein, PIST, as a binding partner for Rho effector
      Rhotekin: biochemical and cell-biological characterization of Rhotekin-PIST
      interaction.
AB  - Among various effector proteins for the small GTPase Rho, the function(s) of
      Rhotekin is (are) almost unknown. We have identified PIST [PDZ (PSD-95, Discs
      large and ZO-1) domain protein interacting specifically with TC10 (a Rho-family
      small GTPase)] as a binding partner for Rhotekin, using yeast two-hybrid
      screening. Rhotekin was found to associate with PIST in vitro and in both
      polarized and non-polarized MDCK (Madin-Darby canine kidney) cells. The C
      terminal SPV (Ser-Pro-Val) motif of Rhotekin exhibited binding to the PDZ domain
      of PIST. The binding was markedly inhibited by an activated version of Rho and
      partially by that of Rac or Cdc42 in COS7 cells. In contrast, TC10 had no effects
      on the binding. Immunofluorescence analyses revealed the co-localization of PIST
      and Rhotekin at the Golgi apparatus in non-polarized fibroblast-like MDCK cells
      and AJs (adherens junctions) in the fully polarized cells. PIST and Rhotekin are
      recruited from the cytosol to AJs as the cell becomes polarized. Expression of
      constitutively active Rho or prevention of Rhotekin-PIST interaction induced
      diffuse cytoplasmic distribution of Rhotekin in polarized MDCK cells. These
      results suggest that there is (1) Rho-dependent regulation of Rhotekin-PIST
      interaction, (2) involvement of PIST in the recruitment of Rhotekin to AJs and
      (3) a possible role(s) for these two proteins in cell-polarity development and/or
      maintenance.

PMID- 16646956
TI  - Assessment of the potential impact of a reminder system on the reduction of
      diagnostic errors: a quasi-experimental study.
AB  - BACKGROUND: Computerized decision support systems (DSS) have mainly focused on
      improving clinicians' diagnostic accuracy in unusual and challenging cases.
      However, since diagnostic omission errors may predominantly result from
      incomplete workup in routine clinical practice, the provision of appropriate
      patient- and context-specific reminders may result in greater impact on patient
      safety. In this experimental study, a mix of easy and difficult simulated cases
      were used to assess the impact of a novel diagnostic reminder system (ISABEL) on
      the quality of clinical decisions made by various grades of clinicians during
      acute assessment. METHODS: Subjects of different grades (consultants, registrars,
      senior house officers and medical students), assessed a balanced set of 24
      simulated cases on a trial website. Subjects recorded their clinical decisions
      for the cases (differential diagnosis, test-ordering and treatment), before and
      after system consultation. A panel of two pediatric consultants independently
      provided gold standard responses for each case, against which subjects' quality
      of decisions was measured. The primary outcome measure was change in the count of
      diagnostic errors of omission (DEO). A more sensitive assessment of the system's
      impact was achieved using specific quality scores; additional consultation time
      resulting from DSS use was also calculated. RESULTS: 76 subjects (18 consultants,
      24 registrars, 19 senior house officers and 15 students) completed a total of 751
      case episodes. The mean count of DEO fell from 5.5 to 5.0 across all subjects
      (repeated measures ANOVA, p < 0.001); no significant interaction was seen with
      subject grade. Mean diagnostic quality score increased after system consultation
      (0.044; 95% confidence interval 0.032, 0.054). ISABEL reminded subjects to
      consider at least one clinically important diagnosis in 1 in 8 case episodes, and
      prompted them to order an important test in 1 in 10 case episodes. Median extra
      time taken for DSS consultation was 1 min (IQR: 30 sec to 2 min). CONCLUSION: The
      provision of patient- and context-specific reminders has the potential to reduce
      diagnostic omissions across all subject grades for a range of cases. This study
      suggests a promising role for the use of future reminder-based DSS in the
      reduction of diagnostic error.

PMID- 16646958
TI  - Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in
      patients with acute bacterial sinusitis.
AB  - BACKGROUND: Acute bacterial sinusitis (ABS) is a common infection in clinical
      practice. Data on time to bacteriologic eradication after antimicrobial therapy
      are lacking for most agents, but are necessary in order to optimize therapy. This
      was a prospective, single-arm, open-label, multicenter study to determine the
      time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated
      with moxifloxacin. METHODS: Adult patients with radiologically and clinically
      confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus
      secretion sampling was performed using nasal endoscopy pre-therapy, and repeated
      on 3 consecutive days during treatment. Target enrollment was 30
      bacteriologically evaluable patients (pre-therapy culture positive for
      Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and
      evaluable cultures for at least Day 2 and Day 3 during therapy visits), including
      at least 10 each with S. pneumoniae or H. influenzae. RESULTS: Of 192 patients
      enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated.
      Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42
      (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%)
      patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23
      H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48;
      85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3.
      On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on
      Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical
      success was achieved in 36/38 (94.7%) patients at the test of cure visit.
      CONCLUSION: In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once
      daily for 10 days resulted in eradication of baseline bacteria in 83.3% of
      patients by Day 2, 100% by Day 3 and 97.6% by Day 4.

PMID- 16646957
TI  - Flexible promoter architecture requirements for coactivator recruitment.
AB  - BACKGROUND: The spatial organization of transcription factor binding sites in
      regulatory DNA, and the composition of intersite sequences, influences the
      assembly of the multiprotein complexes that regulate RNA polymerase recruitment
      and thereby affects transcription. We have developed a genetic approach to
      investigate how reporter gene transcription is affected by varying the spacing
      between transcription factor binding sites. We characterized the components of
      promoter architecture that govern the yeast transcription factors Cbf1 and
      Met31/32, which bind independently, but collaboratively recruit the coactivator
      Met4. RESULTS: A Cbf1 binding site was required upstream of a Met31/32 binding
      site for full reporter gene expression. Distance constraints on coactivator
      recruitment were more flexible than those for cooperatively binding transcription
      factors. Distances from 18 to 50 bp between binding sites support efficient
      recruitment of Met4, with only slight modulation by helical phasing.
      Intriguingly, we found that certain sequences located between the binding sites
      abolished gene expression. CONCLUSION: These results yield insight to the
      influence of both binding site architecture and local DNA flexibility on gene
      expression, and can be used to refine computational predictions of gene
      expression from promoter sequences. In addition, our approach can be applied to
      survey promoter architecture requirements for arbitrary combinations of
      transcription factor binding sites.

PMID- 16646959
TI  - Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage
      0 COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      increased oxidative and nitrosative stress. The aim of our study was to assess
      the importance of these factors in the airways of healthy smokers and symptomatic
      smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.
      METHODS: Exhaled NO (FENO) and induced sputum samples were collected from 22
      current smokers (13 healthy smokers without any respiratory symptoms and 9 with
      symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never
      smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of
      inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and
      4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry.
      Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum
      supernatants by ELISA. RESULTS: FENO was significantly decreased in smokers, mean
      (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced
      sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of
      iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p =
      0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin
      levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore,
      we noted four negative correlations between FENO and 1) total neutrophils (r = 
      0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r =
      -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no
      major differences were found between never smokers and ex-smokers or between
      healthy smokers and stage 0 COPD patients. CONCLUSION: Our results clearly
      indicate that several markers of oxidative/nitrosative stress are increased in
      current cigarette smokers compared to non-smokers and no major differences can be
      observed in these biomarkers between non-symptomatic smokers and subjects with
      GOLD stage 0 COPD.

PMID- 16646960
TI  - Eight previously unidentified mutations found in the OA1 ocular albinism gene.
AB  - BACKGROUND: Ocular albinism type 1 (OA1) is an X-linked ocular disorder
      characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation
      of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in
      pigmented skin and eye cells, and misrouting of the optical tracts. This disease
      is primarily caused by mutations in the OA1 gene. METHODS: The ophthalmologic
      phenotype of the patients and their family members was characterized. We screened
      for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified
      exons, and for genomic deletions by PCR-amplification of large DNA fragments.
      RESULTS: We sequenced the nine exons of the OA1 gene in 72 individuals and found
      ten different mutations in seven unrelated families and three sporadic cases. The
      ten mutations include an amino acid substitution and a premature stop codon
      previously reported by our team, and eight previously unidentified mutations:
      three amino acid substitutions, a duplication, a deletion, an insertion and two
      splice-site mutations. The use of a novel Taq polymerase enabled us to amplify
      large genomic fragments covering the OA1 gene. and to detect very likely six
      distinct large deletions. Furthermore, we were able to confirm that there was no
      deletion in twenty one patients where no mutation had been found. CONCLUSION: The
      identified mutations affect highly conserved amino acids, cause frameshifts or
      alternative splicing, thus affecting folding of the OA1 G protein coupled
      receptor, interactions of OA1 with its G protein and/or binding with its ligand.

PMID- 16646961
TI  - Toxicology as a nanoscience?--disciplinary identities reconsidered.
AB  - Toxicology is about to establish itself as a leading scientific discipline in
      addressing potential health effects of materials on the nanosize level. Entering
      into a cutting-edge field, has an impact on identity-building processes within
      the involved academic fields. In our study, we analyzed the ways in which the
      entry into the field of nanosciences impacts on the formation of disciplinary
      identities. Using the methods of qualitative interviews with particle
      toxicologists in Germany, Holland, Switzerland and the USA, we could demonstrate
      that currently, toxicology finds itself in a transitional phase. The development
      of its disciplinary identity is not yet clear. Nearly all of our interview
      partners stressed the necessity of repositioning toxicology. However, they each
      suggested different approaches. While one part is already propagandizing the
      establishment of a new discipline--'nanotoxicology'--others are more reserved and
      are demanding a clear separation of traditional and new research areas. In phases
      of disciplinary new-orientation, research communities do not act consistently.
      Rather, they establish diverse options. By expanding its disciplinary boundaries,
      participating in new research fields, while continuing its previous research, and
      only vaguely defining its topics, toxicology is feeling its way into the new
      fields without giving up its present self-conception. However, the toxicological
      research community is also discussing a new disciplinary identity. Within this,
      toxicology could develop from an auxiliary into a constitutive position, and take
      over a basic role in the cognitive, institutional and social framing of the
      nanosciences.

PMID- 16646962
TI  - Fast, easy and efficient: site-specific insertion of transgenes into
      enterobacterial chromosomes using Tn7 without need for selection of the insertion
      event.
AB  - BACKGROUND: Inserting transgenes into bacterial chromosomes is generally quite
      involved, requiring a selection for cells carrying the insertion, usually for
      drug-resistance, or multiple cumbersome manipulations, or both. Several
      approaches use phage lambda red recombination, which allows for the possibility
      of mutagenesis of the transgene during a PCR step. RESULTS: We present a simple,
      rapid and highly efficient method for transgene insertion into the chromosome of
      Escherichia coli, Salmonella or Shigella at a benign chromosomal site using the
      site-specific recombination machinery of the transposon Tn7. This method requires
      very few manipulations. The transgene is cloned into a temperature-sensitive
      delivery plasmid and transformed into bacterial cells. Growth at the permissive
      temperature with induction of the recombination machinery leads to transgene
      insertion, and subsequent growth at the nonpermissive temperature cures the
      delivery plasmid. Transgene insertion is highly site-specific, generating
      insertions solely at the Tn7 attachment site and so efficient that it is not
      necessary to select for the insertion. CONCLUSION: This method is more efficient
      and straightforward than other techniques for transgene insertion available for
      E. coli and related bacteria, making moving transgenes from plasmids to a
      chromosomal location a simple matter. The non-requirement for selection is
      particularly well suited for use in development of unmarked strains for
      environmental release, such as live-vector vaccine strains, and also for promoter
      fusion studies, and experiments in which every bacterial cell must express a
      transgene construct.

PMID- 16646963
TI  - A genetic dissection of the LlaJI restriction cassette reveals insights on a
      novel bacteriophage resistance system.
AB  - BACKGROUND: Restriction/modification systems provide the dual function of
      protecting host DNA against restriction by methylation of appropriate bases
      within their recognition sequences, and restriction of foreign invading un
      methylated DNA, such as promiscuous plasmids or infecting bacteriphage. The
      plasmid-encoded LlaJI restriction/modification system from Lactococcus lactis
      recognizes an asymmetric, complementary DNA sequence, consisting of 5'GACGC'3 in
      one strand and 5'GCGTC'3 in the other and provides a prodigious barrier to
      bacteriophage infection. LlaJI is comprised of four similarly oriented genes,
      encoding two 5mC-MTases (M1.LlaJI and M2.LlaJI) and two subunits responsible for
      restriction activity (R1.LlaJI and R2.LlaJI). Here we employ a detailed genetic
      analysis of the LlaJI restriction determinants in an attempt to characterize
      mechanistic features of this unusual hetero-oligomeric endonuclease. RESULTS:
      Detailed bioinformatics analysis confirmed the presence of a conserved GTP
      binding and hydrolysis domain within the C-terminal half of the R1.LlaJI amino
      acid sequence whilst the N-terminal half appeared to be entirely unique. This
      domain architecture was homologous with that of the "B" subunit of the GTP
      dependent, methyl-specific McrBC endonuclease from E.coli K-12. R1.LlaJI did not
      appear to contain a catalytic centre, whereas this conserved motif; PD....D/EXK,
      was clearly identified within the amino acid sequence for R2.LlaJI. Both R1.LlaJI
      and R2.LlaJI were found to be absolutely required for detectable LlaJI activity
      in vivo. The LlaJI restriction subunits were purified and examined in vitro,
      which allowed the assignment of R1.LlaJI as the sole specificity determining
      subunit, whilst R2.LlaJI is believed to mediate DNA cleavage. CONCLUSION: The
      hetero-subunit structure of LlaJI, wherein one subunit mediates DNA binding
      whilst the other subunit is predicted to catalyze strand hydrolysis distinguishes
      LlaJI from previously characterized restriction-modification systems.
      Furthermore, this distinction is accentuated by the fact that whilst LlaJI
      behaves as a conventional Type IIA system in vivo, in that it restricts un
      methylated DNA, it resembles the Type IV McrBC endonuclease, an enzyme specific
      for methylated DNA. A number of similar restriction determinants were identified
      in the database and it is likely LlaJI together with these homologous systems,
      comprise a new subtype of the Type II class incorporating features of Type II and
      Type IV systems.

PMID- 16646964
TI  - Expertise about herbs and dietary supplements among diverse health professionals.
AB  - BACKGROUND: Herbs and other dietary supplements are among the most commonly used
      complementary medical therapies. However, clinicians generally have limited
      knowledge, confidence and communication about herbs and dietary supplements
      (HDS). We compared diverse clinicians' expertise about HDS to better target
      future curricula. METHODS: We conducted a cross-sectional survey of physicians,
      pharmacists, nurses, dietitians and trainees in these professions prior to e
      curriculum about HDS in 2004-2005. The survey had 28 questions about knowledge,
      19 questions about their confidence and 11 questions about their communication
      practices about HDS. RESULTS: Of the 1,268 participants, 25% were male; the
      average age was 40 years. Mean scores were 66% correct for knowledge; 53/95 on
      the confidence scale and 2.2 out of possible 10 on the communication practices
      scale. On average, scores were lowest for those who used fewer HDS; and trainees
      and nurses compared with physicians, pharmacists and dietitians (P < 0.01 for all
      comparisons). CONCLUSION: Clinicians have moderate levels of knowledge and
      confidence, but poor communication skills about HDS. Future curricula about HDS
      should target nurses, students, practitioners and those not currently using HDS.
      Research is needed to determine the most cost-effective educational strategies
      for diverse health professionals.

PMID- 16646965
TI  - Molecular characterization and exclusion of porcine GUSB as a candidate gene for
      congenital hernia inguinalis/scrotalis.
AB  - BACKGROUND: Inguinal hernias are usually caused by a congenital defect, which
      occurs as a weakness of the inguinal canal. Porcine beta-glucuronidase gene
      (GUSB) was chosen as functional candidate gene because of its involvement in
      degradation of hyaluronan within gubernacular tissue during descent of testes.
      Since a genome-wide linkage analysis approach has shown evidence that two regions
      on porcine chromosome 3 (SSC 3) are involved in the inheritance of hernia
      inguinalis/scrotalis in German pig breeds, GUSB also attained status as a
      positional candidate gene by its localization within a hernia-associated
      chromosomal region. RESULTS: A contig spanning 17,157 bp, which contains the
      entire GUSB, was assembled. Comparative sequence analyses were conducted for the
      GUSB gene locus. Single nucleotide polymorphisms (SNPs) located within the coding
      region of GUSB were genotyped in 512 animals. Results of transmission
      disequilibrium test (TDT) for two out of a total of five detected SNPs gave no
      significant association with the outcome of hernia in pigs. CONCLUSION: On the
      basis of our studies we are able to exclude the two analyzed SNPs within the
      porcine GUSB gene as causative for the transmission of inguinal hernia.

PMID- 16646966
TI  - CPR in medical schools: learning by teaching BLS to sudden cardiac death
      survivors--a promising strategy for medical students?
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) training is gaining more
      importance for medical students. There were many attempts to improve the basic
      life support (BLS) skills in medical students, some being rather successful, some
      less. We developed a new problem based learning curriculum, where students had to
      teach CPR to cardiac arrest survivors in order to improve the knowledge about
      life support skills of trainers and trainees. METHODS: Medical students who
      enrolled in our curriculum had to pass a 2 semester problem based learning
      session about the principles of cardiac arrest, CPR, BLS and defibrillation (CPR
      D). Then the students taught cardiac arrest survivors who were randomly chosen
      out of a cardiac arrest database of our emergency department. Both, the student
      and the Sudden Cardiac Death (SCD) survivor were asked about their skills and
      knowledge via questionnaires immediately after the course. The questionnaires
      were then used to evaluate if this new teaching strategy is useful for learning
      CPR via a problem-based-learning course. The survey was grouped into three
      categories, namely "Use of AED", "CPR-D" and "Training". In addition, there was
      space for free answers where the participants could state their opinion in their
      own words, which provided some useful hints for upcoming programs. RESULTS: This
      new learning-by-teaching strategy was highly accepted by all participants, the
      students and the SCD survivors. Most SCD survivors would use their skills in case
      one of their relatives goes into cardiac arrest (96%). Furthermore, 86% of the
      trainees were able to deal with failures and/or disturbances by themselves. On
      the trainer's side, 96% of the students felt to be well prepared for the course
      and were considered to be competent by 96% of their trainees. CONCLUSION: We
      could prove that learning by teaching CPR is possible and is highly accepted by
      the students. By offering a compelling appreciation of what CPR can achieve in
      using survivors from SCD as trainees made them go deeper into the subject of
      resuscitation, what also might result in a longer lasting benefit than regular
      lecture courses in CPR.

PMID- 16646967
TI  - Protocol for the 'e-Nudge trial': a randomised controlled trial of electronic
      feedback to reduce the cardiovascular risk of individuals in general practice
      [ISRCTN64828380].
AB  - BACKGROUND: Cardiovascular disease (including coronary heart disease and stroke)
      is a major cause of death and disability in the United Kingdom, and is to a large
      extent preventable, by lifestyle modification and drug therapy. The recent
      standardisation of electronic codes for cardiovascular risk variables through the
      United Kingdom's new General Practice contract provides an opportunity for the
      application of risk algorithms to identify high risk individuals. This randomised
      controlled trial will test the benefits of an automated system of alert messages
      and practice searches to identify those at highest risk of cardiovascular disease
      in primary care databases. DESIGN: Patients over 50 years old in practice
      databases will be randomised to the intervention group that will receive the
      alert messages and searches, and a control group who will continue to receive
      usual care. In addition to those at high estimated risk, potentially high risk
      patients will be identified who have insufficient data to allow a risk estimate
      to be made. Further groups identified will be those with possible undiagnosed
      diabetes, based either on elevated past recorded blood glucose measurements, or
      an absence of recent blood glucose measurement in those with established
      cardiovascular disease. OUTCOME MEASURES: The intervention will be applied for
      two years, and outcome data will be collected for a further year. The primary
      outcome measure will be the annual rate of cardiovascular events in the
      intervention and control arms of the study. Secondary measures include the
      proportion of patients at high estimated cardiovascular risk, the proportion of
      patients with missing data for a risk estimate, and the proportion with undefined
      diabetes status at the end of the trial.

PMID- 16646968
TI  - The relationship between organisational characteristics and the effects of
      clinical guidelines on medical performance in hospitals, a meta-analysis.

PMID- 16646969
TI  - Metabolomic database annotations via query of elemental compositions: mass
      accuracy is insufficient even at less than 1 ppm.
AB  - BACKGROUND: Metabolomic studies are targeted at identifying and quantifying all
      metabolites in a given biological context. Among the tools used for metabolomic
      research, mass spectrometry is one of the most powerful tools. However,
      metabolomics by mass spectrometry always reveals a high number of unknown
      compounds which complicate in depth mechanistic or biochemical understanding. In
      principle, mass spectrometry can be utilized within strategies of de novo
      structure elucidation of small molecules, starting with the computation of the
      elemental composition of an unknown metabolite using accurate masses with errors
      <5 ppm (parts per million). However even with very high mass accuracy (<1 ppm)
      many chemically possible formulae are obtained in higher mass regions. In
      automatic routines an additional orthogonal filter therefore needs to be applied
      in order to reduce the number of potential elemental compositions. This report
      demonstrates the necessity of isotope abundance information by mathematical
      confirmation of the concept. RESULTS: High mass accuracy (<1 ppm) alone is not
      enough to exclude enough candidates with complex elemental compositions (C, H, N,
      S, O, P, and potentially F, Cl, Br and Si). Use of isotopic abundance patterns as
      a single further constraint removes >95% of false candidates. This orthogonal
      filter can condense several thousand candidates down to only a small number of
      molecular formulas. Example calculations for 10, 5, 3, 1 and 0.1 ppm mass
      accuracy are given. Corresponding software scripts can be downloaded from
      http://fiehnlab.ucdavis.edu. A comparison of eight chemical databases revealed
      that PubChem and the Dictionary of Natural Products can be recommended for
      automatic queries using molecular formulae. CONCLUSION: More than 1.6 million
      molecular formulae in the range 0-500 Da were generated in an exhaustive manner
      under strict observation of mathematical and chemical rules. Assuming that ion
      species are fully resolved (either by chromatography or by high resolution mass
      spectrometry), we conclude that a mass spectrometer capable of 3 ppm mass
      accuracy and 2% error for isotopic abundance patterns outperforms mass
      spectrometers with less than 1 ppm mass accuracy or even hypothetical mass
      spectrometers with 0.1 ppm mass accuracy that do not include isotope information
      in the calculation of molecular formulae.

PMID- 16646970
TI  - Scratch lottery tickets are a poor incentive to respond to mailed questionnaires.
AB  - BACKGROUND: It has been demonstrated that the enclosure of money with a mailed
      questionnaire increases the response rate significantly. We evaluated scratch
      lottery tickets as an alternative to cash. METHODS: 1500 randomly selected
      Norwegians between the ages of 40 and 65 years were sent a short questionnaire.
      250 received one lottery scratch ticket worth 20 Norwegian kroner (approximately
      3 USD) together with the questionnaire, 250 received two scratch tickets, and 250
      were promised two scratch tickets if they replied within one week. A fourth group
      of 250 persons received a 50 kroner banknote with the questionnaire. The
      remaining 500 letters served as controls. RESULTS: The overall response rate
      after 6 weeks was 77%. Logistic regression analysis showed that only the 50
      kroner group had a response rate that was statistically significantly higher than
      the controls (p < 0.0001). It was also significantly higher than that in any of
      the other incentive groups (p < 0.0001, p < 0.004 and p < 0.0001 respectively).
      Female sex (p < 0.001) and age (p < 0.002) increased the response rate
      significantly. CONCLUSION: It is possible that the recipients scratched their
      cards before completing the questionnaire, and that it was a disincentive for the
      majority that they did not win anything. Lottery scratch tickets are no
      substitute for cash as an incentive to respond to a questionnaire.

PMID- 16646971
TI  - Phylogenomic analysis of the GIY-YIG nuclease superfamily.
AB  - BACKGROUND: The GIY-YIG domain was initially identified in homing endonucleases
      and later in other selfish mobile genetic elements (including restriction enzymes
      and non-LTR retrotransposons) and in enzymes involved in DNA repair and
      recombination. However, to date no systematic search for novel members of the GIY
      YIG superfamily or comparative analysis of these enzymes has been reported.
      RESULTS: We carried out database searches to identify all members of known GIY
      YIG nuclease families. Multiple sequence alignments together with predicted
      secondary structures of identified families were represented as Hidden Markov
      Models (HMM) and compared by the HHsearch method to the uncharacterized protein
      families gathered in the COG, KOG, and PFAM databases. This analysis allowed for
      extending the GIY-YIG superfamily to include members of COG3680 and a number of
      proteins not classified in COGs and to predict that these proteins may function
      as nucleases, potentially involved in DNA recombination and/or repair. Finally,
      all old and new members of the GIY-YIG superfamily were compared and analyzed to
      infer the phylogenetic tree. CONCLUSION: An evolutionary classification of the
      GIY-YIG superfamily is presented for the very first time, along with the
      structural annotation of all (sub)families. It provides a comprehensive picture
      of sequence-structure-function relationships in this superfamily of nucleases,
      which will help to design experiments to study the mechanism of action of known
      members (especially the uncharacterized ones) and will facilitate the prediction
      of function for the newly discovered ones.

PMID- 16646972
TI  - Pontiac fever: an operational definition for epidemiological studies.
AB  - BACKGROUND: Pontiac fever is usually described in epidemic settings. Detection of
      Pontiac fever is a marker of an environmental contamination by Legionella and
      should thereby call for prevention measures in order to prevent outbreak of
      Legionnaire's disease. The objective of this study is to propose an operational
      definition of Pontiac fever that is amenable to epidemiological surveillance and
      investigation in a non epidemic setting. METHODS: A population of 560 elderly
      subjects residing in 25 nursing homes was followed during 4 months in order to
      assess the daily incidence of symptoms associated, in the literature, with
      Pontiac fever. The water and aerosol of one to 8 showers by nursing home were
      characterized combining conventional bacterial culture of Legionella and the
      Fluorescence In Situ Hybridization (FISH) technique that used oligonucleotides
      probes specific for Legionellaceae. A definition of Pontiac fever was devised
      based on clinical symptoms described in epidemic investigations and on their
      timing after the exposure event. The association between incidence of Pontiac
      fever and shower contamination levels was evaluated to test the relevance of this
      definition. RESULTS: The proposed definition of Pontiac fever associated the
      following criteria: occurrence of at least one symptom among headache, myalgia,
      fever and shivers, possibly associated with other 'minor' symptoms, within three
      days after a shower contaminated by Legionella, during a maximum of 8 days
      (minimum 2 days). 23 such cases occurred during the study (incidence rate: 0.125
      cases per person-year [95% CI: 0.122-0.127]). A concentration of Legionella in
      water equal to or greater than 10(4).L(-1) (FISH method) was associated with a
      significant increase of incidence of Pontiac fever (p = 0.04). CONCLUSION: Once
      validated in other settings, the proposed definition of Pontiac fever might be
      used to develop epidemiological surveillance and help draw attention on sources
      of Legionella.

PMID- 16646973
TI  - The characterization of amphibian nucleoplasmins yields new insight into their
      role in sperm chromatin remodeling.
AB  - BACKGROUND: Nucleoplasmin is a nuclear chaperone protein that has been shown to
      participate in the remodeling of sperm chromatin immediately after fertilization
      by displacing highly specialized sperm nuclear basic proteins (SNBPs), such as
      protamine (P type) and protamine-like (PL type) proteins, from the sperm
      chromatin and by the transfer of histone H2A-H2B. The presence of SNBPs of the
      histone type (H type) in some organisms (very similar to the histones found in
      somatic tissues) raises uncertainty about the need for a nucleoplasmin-mediated
      removal process in such cases and poses a very interesting question regarding the
      appearance and further differentiation of the sperm chromatin remodeling function
      of nucleoplasmin and the implicit relationship with SNBP diversity The amphibians
      represent an unique opportunity to address this issue as they contain genera with
      SNBPs representative of each of the three main types: Rana (H type); Xenopus (PL
      type) and Bufo (P type). RESULTS: In this work, the presence of nucleoplasmin in
      oocyte extracts from these three organisms has been assessed using Western
      Blotting. We have used mass spectrometry and cloning techniques to characterize
      the full-length cDNA sequences of Rana catesbeiana and Bufo marinus
      nucleoplasmin. Northern dot blot analysis shows that nucleoplasmin is mainly
      transcribed in the egg of the former species. Phylogenetic analysis of
      nucleoplasmin family members from various metazoans suggests that amphibian
      nucleoplasmins group closely with mammalian NPM2 proteins. CONCLUSION: We have
      shown that these organisms, in striking contrast to their SNBPs, all contain
      nucleoplasmins with very similar primary structures. This result has important
      implications as it suggests that nucleoplasmin's role in chromatin assembly
      during early zygote development could have been complemented by the acquisition
      of a new function of non-specifically removing SNBPs in sperm chromatin
      remodeling. This acquired function would have been strongly determined by the
      constraints imposed by the appearance and differentiation of SNBPs in the sperm.

PMID- 16646974
TI  - Insomnia in school-age children with Asperger syndrome or high-functioning
      autism.
AB  - BACKGROUND: Asperger syndrome (AS) and high-functioning autism (HFA) are
      pervasive developmental disorders (PDD) in individuals of normal intelligence.
      Childhood AS/HFA is considered to be often associated with disturbed sleep, in
      particular with difficulties initiating and/or maintaining sleep (insomnia).
      However, studies about the topic are still scarce. The present study investigated
      childhood AS/HFA regarding a wide range of parent reported sleep-wake behaviour,
      with a particular focus on insomnia. METHODS: Thirty-two 8-12 yr old children
      with AS/HFA were compared with 32 age and gender matched typically developing
      children regarding sleep and associated behavioural characteristics. Several
      aspects of sleep-wake behaviour including insomnia were surveyed using a
      structured paediatric sleep questionnaire in which parents reported their
      children's sleep patterns for the previous six months. Recent sleep patterns were
      monitored by use of a one-week sleep diary and actigraphy. Behavioural
      characteristics were surveyed by use of information gleaned from parent and
      teacher-ratings in the High-Functioning Autism Spectrum Screening Questionnaire,
      and in the Strengths and Difficulties Questionnaire. RESULTS: Parent-reported
      difficulties initiating sleep and daytime sleepiness were more common in children
      with AS/HFA than in controls, and 10/32 children with AS/HFA (31.2%) but none of
      the controls fulfilled our definition of paediatric insomnia. The parent-reported
      insomnia corresponded to the findings obtained by actigraphy. Children with
      insomnia had also more parent-reported autistic and emotional symptoms, and more
      teacher-reported emotional and hyperactivity symptoms than those children without
      insomnia. CONCLUSION: Parental reports indicate that in childhood AS/HFA insomnia
      is a common and distressing symptom which is frequently associated with
      coexistent behaviour problems. Identification and treatment of sleep problems
      need to be a routine part of the treatment plan for children with AS/HFA.

PMID- 16646975
TI  - A reminder of the association between Clostridium septicum and colonic
      adenocarcinoma.
AB  - We present the case of a patient, with previously unknown liver metastases,
      presenting with a liver abscess and Clostridium septicum septicaemia. C. septicum
      is known to be associated with both malignancy and immunosuppression and
      therefore in patients where this organism is isolated, efforts must be made to
      exclude an occult underlying malignancy or haematological disorder.

PMID- 16646976
TI  - Hyeropic shift after LASIK induced diffuse lamellar keratitis.
AB  - BACKGROUND: Diffuse lamellar keratitis (DLK) is a relatively new syndrome that is
      increasingly being reported after LASIK. We have observed that a hyperopic shift
      may be associated with the occurrence of this diffuse lamellar keratitis. CASE
      PRESENTATION: A 26 year old man developed bilateral diffuse lamellar keratitis
      (DLK) following myopic LASIK. The residual refractive error was +0.5D OD and
      +0.25D OS at the end of the first week. The sterile infiltrates resolved over a
      period of 4-6 weeks on topical steroid therapy. A progressive hyperopic shift was
      noted in the right eye with an error +4.25Dsph/+0.25Dcyl 20 at the final follow
      up 6 months post surgery. CONCLUSION: Diffuse lamellar keratitis after LASIK may
      be associated with a significant hyperopic shift.

PMID- 16646977
TI  - Dense breast stromal tissue shows greatly increased concentration of breast
      epithelium but no increase in its proliferative activity.
AB  - INTRODUCTION: Increased mammographic density is a strong risk factor for breast
      cancer. The reasons for this are not clear; two obvious possibilities are
      increased epithelial cell proliferation in mammographically dense areas and
      increased breast epithelium in women with mammographically dense breasts. We
      addressed this question by studying the number of epithelial cells in terminal
      duct lobular units (TDLUs) and in ducts, and their proliferation rates, as they
      related to local breast densities defined histologically within individual women.
      METHOD: We studied deep breast tissue away from subcutaneous fat obtained from 12
      healthy women undergoing reduction mammoplasty. A slide from each specimen was
      stained with the cell-proliferation marker MIB1. Each slide was divided into
      (sets of) areas of low, medium and high density of connective tissue (CT; highly
      correlated with mammographic densities). Within each of the areas, the numbers of
      epithelial cells in TDLUs and ducts, and the numbers MIB1 positive, were counted.
      RESULTS: The relative concentration (RC) of epithelial cells in high compared
      with low CT density areas was 12.3 (95% confidence interval (CI) 10.9 to 13.8) in
      TDLUs and 34.1 (95% CI 26.9 to 43.2) in ducts. There was a much smaller
      difference between medium and low CT density areas: RC = 1.4 (95% CI 1.2 to 1.6)
      in TDLUs and 1.9 (95% CI 1.5 to 2.3) in ducts. The relative mitotic rate (RMR;
      MIB1 positive) of epithelial cells in high compared with low CT density areas was
      0.59 (95% CI 0.53 to 0.66) in TDLUs and 0.65 (95% CI 0.53 to 0.79) in ducts; the
      figures for the comparison of medium with low CT density areas were 0.58 (95% CI
      0.48 to 0.70) in TDLUs and 0.66 (95% CI 0.44 to 0.97) in ducts. CONCLUSION:
      Breast epithelial cells are overwhelmingly concentrated in high CT density areas.
      Their proliferation rate in areas of high and medium CT density is lower than
      that in low CT density areas. The increased breast cancer risk associated with
      increased mammographic densities may simply be a reflection of increased
      epithelial cell numbers. Why epithelium is concentrated in high CT density areas
      remains to be explained.

PMID- 16646978
TI  - The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators
      by synovial fibroblasts and articular chondrocytes.
AB  - Six novel members of the IL-1 family of cytokines were recently identified,
      primarily through the use of DNA database searches for IL-1 homologues, and were
      named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL
      1F8 on primary human joint cells, and examined the expression of the new IL-1
      family members in human and mouse joints. Human synovial fibroblasts (hSFs) and
      human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and
      produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8
      mRNA expression was increased in hSFs upon stimulation with proinflammatory
      cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL
      1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore,
      although IL-1beta protein levels were increased in inflamed human and mouse joint
      tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were
      similar to or lower than those in matched serum samples, suggesting that the
      joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar
      in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and
      septic shock, and did not correlate with inflammatory status. Interestingly
      however, we observed high IL-1F8 levels in several serum samples in all groups.
      In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint
      cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation,
      but they were high in some human serum samples tested, including samples from
      patients with rheumatoid arthritis. It remains to be determined whether
      circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis.

PMID- 16646979
TI  - Osteogenic protein 1 in synovial fluid from patients with rheumatoid arthritis or
      osteoarthritis: relationship with disease and levels of hyaluronan and antigenic
      keratan sulfate.
AB  - The measurement of body fluid levels of biochemical markers in joint tissues has
      begun to provide clinically useful information. Synovial fluid (SF) plays an
      important role in articular joint lubrication, nutrition, and metabolism of
      cartilage and other connective tissues within the joint. The purpose of our study
      was to identify and characterize osteogenic protein 1 (OP-1) in SF from patients
      with rheumatoid arthritis (RA) or with osteoarthritis (OA) and to correlate
      levels of OP-1 with those of hyaluronan (HA) and antigenic keratan sulfate
      (AgKS). SF was aspirated from the knees of patients with either RA or OA and from
      the knees of asymptomatic organ donors with no documented history of joint
      disease. The presence of detectable OP-1 in SF was demonstrated by western blots
      with specific anti-pro-OP-1 and anti-mature OP-1 antibodies. Measurement of
      levels of OP-1, HA and AgKS was performed using ELISAs. OP-1 was identified in
      human SF in two forms, pro-OP-1 and active (mature) OP-1--mature OP-1 being
      detected only in SF from OA patients and RA patients. Levels of OP-1 and HA were
      higher in RA patients than in OA patients and asymptomatic donors, while the
      level of AgKS was highest in SF from asymptomatic donors. Statistically
      significant differences were found between SF levels of OP-1 in RA and OA
      patients and between SF levels of AgKS among the three groups tested. The SF
      content of OP-1 tended to correlate positively with HA levels, but negatively
      with AgKS concentrations. In conclusion, the results of this study suggest that
      measurement of OP-1 in joint fluid may have value in the clinical evaluation of
      joint disease processes.

PMID- 16646980
TI  - Cyclooxygenases and prostaglandin E2 receptors in growth plate chondrocytes in
      vitro and in situ--prostaglandin E2 dependent proliferation of growth plate
      chondrocytes.
AB  - Prostaglandin E2 (PGE2) plays an important role in bone development and
      metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge
      about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is
      essential. We therefore examined the production of PGE2 in cultured growth plate
      chondrocytes in vitro and the effects of exogenously added PGE2 on cell
      proliferation. Furthermore, we analysed the expression and spatial distribution
      of cyclooxygenase (COX)-1 and COX-2 and PGE2 receptor types EP1, EP2, EP3 and EP4
      in the growth plate in situ and in vitro. PGE2 synthesis was determined by mass
      spectrometry, cell proliferation by DNA [3H]-thymidine incorporation, mRNA
      expression of cyclooxygenases and EP receptors by RT-PCR on cultured cells and in
      homogenized growth plates. To determine cellular expression, frozen sections of
      rat tibial growth plate and primary chondrocyte cultures were stained using
      immunohistochemistry with polyclonal antibodies directed towards COX-1, COX-2,
      EP1, EP2, EP3, and EP4. Cultured growth plate chondrocytes transiently secreted
      PGE2 into the culture medium. Although both enzymes were expressed in
      chondrocytes in vitro and in vivo, it appears that mainly COX-2 contributed to
      PGE2-dependent proliferation. Exogenously added PGE2 stimulated DNA synthesis in
      a dose-dependent fashion and gave a bell-shaped curve with a maximum at 10-8 M.
      The EP1/EP3 specific agonist sulprostone and the EP1-selective agonist ONO-D1-004
      increased DNA synthesis. The effect of PGE2 was suppressed by ONO-8711. The
      expression of EP1, EP2, EP3, and EP4 receptors in situ and in vitro was observed;
      EP2 was homogenously expressed in all zones of the growth plate in situ, whereas
      EP1 expression was inhomogenous, with spared cells in the reserve zone. In
      cultured cells these four receptors were expressed in a subset of cells only. The
      most intense staining for the EP1 receptor was found in polygonal cells
      surrounded by matrix. Expression of receptor protein for EP3 and EP4 was observed
      also in rat growth plates. In cultured chrondrocytes, however, only weak
      expression of EP3 and EP4 receptor was detected. We suggest that in growth plate
      chondrocytes, COX-2 is responsible for PGE2 release, which stimulates cell
      proliferation via the EP1 receptor.

PMID- 16646981
TI  - Activation of transforming growth factor-beta1 and early atherosclerosis in
      systemic lupus erythematosus.
AB  - The efficiency of activating latent transforming growth factor (TGF)-beta1 in
      systemic lupus erythematosus (SLE) may control the balance between inflammation
      and fibrosis, modulating the disease phenotype. To test this hypothesis we
      studied the ability to activate TGF-beta1 in SLE patients and control individuals
      within the context of inflammatory disease activity, cumulative organ damage and
      early atherosclerosis. An Activation Index (AI) for TGF-beta1 was determined for
      32 patients with SLE and 33 age-matched and sex-matched control individuals by
      quantifying the increase in active TGF-beta1 under controlled standard
      conditions. Apoptosis in peripheral blood mononuclear cells was determined by
      fluorescence-activated cell sorting. Carotid artery intima-media thickness was
      measured using standard Doppler ultrasound. These measures were compared between
      patients and control individuals. In an analysis conducted in patients, we
      assessed the associations of these measures with SLE phenotype, including early
      atherosclerosis. Both intima-media thickness and TGF-beta1 AI for SLE patients
      were within the normal range. There was a significant inverse association between
      TGF-beta1 AI and levels of apoptosis in peripheral blood mononuclear cells after
      24 hours in culture for both SLE patients and control individuals. Only in SLE
      patients was there a significant negative correlation between TGF-beta1 AI and
      low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-beta1
      AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI
      was associated with irreversible damage (SLICC [Systemic Lupus International
      Collaborating Clinics] Damage Index > or = 1) and was inversely correlated with
      disease duration. Intima-media thickness was significantly linked to total
      cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-beta1
      activation was linked with increased lymphocyte apoptosis, irreversible organ
      damage, disease duration, calculated low-density lipoprotein levels and increased
      carotid IMT, and may contribute to the development of early atherosclerosis.

PMID- 16646982
TI  - Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid
      arthritis.
AB  - Recently, we proposed a classification of HLA-DRB1 alleles that reshapes the
      shared epitope hypothesis in rheumatoid arthritis (RA); according to this model,
      RA is associated with the RAA shared epitope sequence (72-74 positions) and the
      association is modulated by the amino acids at positions 70 and 71, resulting in
      six genotypes with different RA risks. This was the first model to take into
      account the association between the HLA-DRB1 gene and RA, and linkage data for
      that gene. In the present study we tested this classification for validity in an
      independent sample. A new sample of the same size and population (100 RA French
      Caucasian families) was genotyped for the HLA-DRB1 gene. The alleles were grouped
      as proposed in the new classification: S1 alleles for the sequences A-RAA or E
      RAA; S2 for Q or D-K-RAA; S3D for D-R-RAA; S3P for Q or R-R-RAA; and X alleles
      for no RAA sequence. Transmission of the alleles was investigated. Genotype odds
      ratio (OR) calculations were performed through conditional logistic regression,
      and we tested the homogeneity of these ORs with those of the 100 first trio
      families (one case and both parents) previously reported. As previously observed,
      the S2 and S3P alleles were significantly over-transmitted and the S1, S3D and X
      alleles were under-transmitted. The latter were grouped as L alleles, resulting
      in the same three-allele classification. The risk hierarchy of the six derived
      genotypes was the same: (by decreasing OR and with L/L being the reference
      genotype) S2/S3P, S2/S2, S3P/S3P, S2/L and S3P/L. The homogeneity test between
      the ORs of the initial and the replication samples revealed no significant
      differences. The new classification was therefore considered validated, and both
      samples were pooled to provide improved estimates of RA risk genotypes from the
      highest (S2/S3P [OR 22.2, 95% confidence interval 9.9-49.7]) to the lowest (S3P/L
      [OR 4.4, 95% confidence interval 2.3-8.4]).

PMID- 16646983
TI  - Bone erosions in rheumatoid arthritis can be repaired through reduction in
      disease activity with conventional disease-modifying antirheumatic drugs.
AB  - We conducted the present study to determine whether repair of erosions occurs in
      patients with rheumatoid arthritis (RA) treated with conventional disease
      modifying anti-rheumatic drugs (DMARDs) and to compare clinical characteristics
      between patients exhibiting and not exhibiting erosion repair. We included in the
      study a total of 122 RA patients who fulfilled the 1987 American College of
      Rheumatology criteria for RA; all patients had paired sequential radiographs of
      both hands and wrists showing erosive changes at baseline. Patients were
      classified into two groups according to the presence of repair of erosions at
      follow up, namely the 'repair observed' and 'repair not observed' groups.
      Clinical characteristics, disease activity, radiographic scores and treatment in
      the two groups were compared. Forty-four repairs were observed in 13 patients
      (10.7%). Compared with the repair not observed group, the functional class of the
      patients in the repair observed group was lower at baseline (P < 0.01) and the
      mean disease activity was lower at follow up (P < 0.005). The changes in
      radiographic scores per year (total radiographic score and erosion score) were
      lower (P < 0.05 and P < 0.01, respectively) in the repair observed group. No
      difference in treatment was observed. Repair of erosions was detected in 10.7% of
      RA patients treated with conventional DMARDs. Repairs were associated with low
      functional class at baseline and low disease activity at follow up. These
      observations support the importance of reduction in disease activity in RA
      patients. Because repair of erosions was detected in a substantial number of
      patients, assessment of erosion repair should be incorporated into the
      radiographic evaluation and scoring of RA.

PMID- 16646984
TI  - Novel gene and gene model detection using a whole genome open reading frame
      analysis in proteomics.
AB  - BACKGROUND: Defining the location of genes and the precise nature of gene
      products remains a fundamental challenge in genome annotation. Interrogating
      tandem mass spectrometry data using genomic sequence provides an unbiased method
      to identify novel translation products. A six-frame translation of the entire
      human genome was used as the query database to search for novel blood proteins in
      the data from the Human Proteome Organization Plasma Proteome Project. Because
      this target database is orders of magnitude larger than the databases
      traditionally employed in tandem mass spectra analysis, careful attention to
      significance testing is required. Confidence of identification is assessed using
      our previously described Poisson statistic, which estimates the significance of
      multi-peptide identifications incorporating the length of the matching sequence,
      number of spectra searched and size of the target sequence database. RESULTS:
      Applying a false discovery rate threshold of 0.05, we identified 282 significant
      open reading frames, each containing two or more peptide matches. There were 627
      novel peptides associated with these open reading frames that mapped to a unique
      genomic coordinate placed within the start/stop points of previously annotated
      genes. These peptides matched 1,110 distinct tandem MS spectra. Peptides fell
      into four categories based upon where their genomic coordinates placed them
      relative to annotated exons within the parent gene. CONCLUSION: This work
      provides evidence for novel alternative splice variants in many previously
      annotated genes. These findings suggest that annotation of the genome is not yet
      complete and that proteomics has the potential to further add to our
      understanding of gene structures.

PMID- 16646985
TI  - Solute removal during continuous renal replacement therapy in critically ill
      patients: convection versus diffusion.
AB  - INTRODUCTION: The best modality, for continuous renal replacement therapy (CRRT)
      is currently uncertain and it is poorly understood how transport of different
      solutes, whether convective or diffusive, changes over time. METHODS: We
      conducted a prospective cross over study in a cohort of critically ill patients,
      comparing small (urea and creatinine) and middle (beta2 microglobulin) molecular
      weight solute clearance, filter lifespan and membrane performance over a period
      of 72 hours, during 15 continuous veno-venous dialysis (CVVHD) and 15 continuous
      veno-venous hemofiltration (CVVH)sessions. Both modalities were administered
      based on a prescription of 35 ml/kg/h and using polyacrylonitrile filters.
      RESULTS: Median filter lifespan was significantly longer during CVVHD (37 hours,
      interquartile range (IQR) 19.5 to 72.5) than CVVH (19 hours, IQR 12.5 to 28) (p =
      0.03). Median urea time weighted average (TWA) clearances were not significantly
      different during CVVH (31.6 ml/minute, IQR 23.2 to 38.9) and CVVHD (35.7
      ml/minute, IQR 30.1 to 41.5) (p = 0.213). Similar results were found for
      creatinine: 38.1 ml/minute, IQR 28.5 to 39, and 35.6 ml/minute, IQR 26 to 43 (p =
      0.917), respectively. Median beta2m TWA clearance was higher during convective
      (16.3 ml/minute, IQR 10.9 to 23) than diffusive (6.27 ml/minute, IQR 1.6 to 14.9)
      therapy; nonetheless this difference did not reach statistical significance (p =
      0.055). Median TWA adsorptive clearance of beta2m appeared to have scarce impact
      on overall solute removal (0.012 ml/minute, IQR -0.09 to 0.1, during
      hemofiltration versus -0.016 ml/minute, IQR -0.08 to 0.1 during dialysis; p =
      0.79). Analysis of clearance modification over time did not show significant
      modifications of urea, creatinine and beta2m clearance in the first 48 hours
      during both treatments. In the CVVHD group, the only significant difference was
      found for beta2m between 72 hours and baseline clearance. CONCLUSION:
      Polyacrylonitrile filters during continuous hemofiltration and continuous
      hemodialysis delivered at 35 ml/kg/h are comparable in little and middle size
      solute removal. CVVHD appears to warrant longer CRRT sessions. The capacity of
      both modalities for removing such molecules is maintained up to 48 hours.

PMID- 16646986
TI  - Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the
      intensive care unit--a homogeneous population?
AB  - INTRODUCTION: Acute tubular necrosis (ATN) is usually studied as a single entity,
      without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In
      the present study we evaluated the characteristics and outcomes of patients with
      ATN by aetiological group. METHOD: We conducted a retrospective comparison of
      clinical features, mortality rates and risk factors for mortality for the three
      types of ATN in patients admitted to the general intensive care unit of a
      university hospital between 1997 and 2000. RESULTS: Of 593 patients with acute
      renal failure, 524 (88%) were classified as having ATN. Their mean age was 58
      years, 68% were male and 52% were surgical patients. The overall mortality rate
      was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed
      ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in
      terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ
      failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%)
      than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute
      renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and
      hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality
      was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than
      for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and
      all patients combined were analyzed by multivariate logistic regression, the
      independent factors for mortality identified were different except for oliguria,
      which was the only variable universally associated with death (odds ratio [OR]
      3.0, 95% confidence interval [CI] 1.64-5.49 [P = 0.0003] for ischaemic ATN; OR
      1.96, 95% CI 1.04-3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60-3.76
      [P < 0.001] for all patients combined]). CONCLUSION: The frequency of isolated
      nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90%
      of cases. The three forms of ATN exhibited different clinical characteristics.
      Mortality was strikingly higher in ischaemic and mixed ATN than in nephrotoxic
      ATN. Although the type of ATN was not an independent predictor of death, the
      independent factors related to mortality were different for ischaemic, mixed and
      all patients combined. These data indicate that the three types of ATN represent
      different patient populations, which should be taken into consideration in future
      studies.

PMID- 16646987
TI  - Efficacy and safety of non-invasive ventilation in the treatment of acute
      cardiogenic pulmonary edema--a systematic review and meta-analysis.
AB  - INTRODUCTION: Continuous positive airway pressure ventilation (CPAP) and non
      invasive positive pressure ventilation (NPPV) are accepted treatments in acute
      cardiogenic pulmonary edema (ACPE). However, it remains unclear whether NPPV is
      better than CPAP in reducing the need for endotracheal intubation (NETI) rates,
      mortality and other adverse events. Our aim was to review the evidence about the
      efficacy and safety of these two methods in ACPE management. METHODS: We
      conducted a systematic review and meta-analysis of randomized controlled trials
      on the effect of CPAP and/or NIPV in the treatment of ACPE, considering the
      outcomes NETI, mortality and incidence of acute myocardial infarction (AMI). We
      searched six electronic databases up to May 2005 without language restrictions,
      reviewed references of relevant articles, hand searched conference proceedings
      and contacted experts. RESULTS: Of 790 articles identified, 17 were included. In
      a pooled analysis, 10 studies of CPAP compared to standard medical therapy (SMT)
      showed a significant 22% absolute risk reduction (ARR) in NETI (95% confidence
      interval (CI), -34% to -10%) and 13% in mortality (95%CI, -22% to -5%). Six
      studies of NPPV compared to SMT showed an 18% ARR in NETI (95%CI, -32% to -4%)
      and 7% in mortality (95%CI, -14% to 0%). Seven studies of NPPV compared to CPAP
      showed a non-significant 3% ARR in NETI (95%CI, -4% to 9%) and 2% in mortality
      (95%CI, -6% to 10%). None of these methods increased AMI risk. In a subgroup
      analysis, NPPV did not lead to better outcomes than CPAP in studies including
      more hypercapnic patients. CONCLUSION: Robust evidence now supports the use of
      CPAP and NPPV in ACPE. Both techniques decrease NETI and mortality compared to
      SMT and none shows increased AMI risk. CPAP should be considered a first line
      intervention as NPPV did not show a better efficacy, even in patients with more
      severe conditions, and CPAP is cheaper and easier to implement in clinical
      practice.

PMID- 16646988
TI  - Folate-targeted immunotherapy effectively treats established adjuvant and
      collagen-induced arthritis.
AB  - Activated macrophages express a cell surface receptor for the vitamin folic acid.
      Because this receptor is inaccessible or not measurably expressed on other normal
      cells, folic acid has been recently exploited to selectively deliver attached
      radio-emitters to sites of activated macrophage accumulation, allowing
      scintigraphic imaging of inflamed joints and organs of arthritic rats. We
      demonstrate here that folate-linked haptens can also be targeted to activated
      macrophages, decorating their cell surfaces with highly immunogenic molecules.
      Under conditions in which the rodent has already been immunized against keyhole
      limpet hemocyanine-(fluorescein isothiocyanate) FITC, activated macrophages are
      eliminated. Administration of folate-FITC conjugates to rodents with experimental
      arthritis attenuates (a) systemic and peri-articular inflammation, (b) bone and
      cartilage degradation, and (c) arthritis-related body weight loss. Treatment with
      folate-hapten conjugates is comparable to methotrexate, etanercept, anakinra, and
      celecoxib at alleviating the symptoms of arthritis. We conclude that reduction of
      activated macrophages by folate-targeted immunotherapy can ameliorate the
      symptoms of arthritis in two rodent models of the disease.

PMID- 16646989
TI  - Atherogenic lipid profile is a feature characteristic of patients with early
      rheumatoid arthritis: effect of early treatment--a prospective, controlled study.
AB  - We investigated lipid profiles and lipoprotein modification after immuno
      intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight
      patients with ERA who met the American College of Rheumatology (ACR) criteria
      were included in the study. These patients had disease durations of less than one
      year and had not had prior treatment for it. Smokers or patients suffering from
      diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome,
      obesity, familiar dyslipidemia and those receiving medications affecting lipid
      metabolism were excluded from the study. Sixty-three healthy volunteers
      (controls) were also included. Patients were treated with methotrexate and
      prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS
      28) as well as ACR 50% response criteria were determined for all patients. The
      mean DAS-28 at disease onset was 5.8 +/- 0.9. After a year of therapy, 53 (91.3%)
      patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the
      ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA
      patients exhibited higher serum levels of total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high
      density lipoprotein cholesterol (HDL-C) levels were significantly lower compared
      to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that
      of LDL-C/HDL-C was significantly higher in ERA patients compared to controls.
      After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as
      well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the
      increase of serum HDL-C levels. These changes were inversely correlated with
      laboratory changes, especially CRP and ESR. In conclusion, ERA patients are
      characterized by an atherogenic lipid profile, which improves after therapy.
      Thus, early immuno-intervention to control disease activity may reduce the risk
      of the atherosclerotic process and cardiovascular events in ERA patients.

PMID- 16646990
TI  - KIAA0101 (OEACT-1), an expressionally down-regulated and growth-inhibitory gene
      in human hepatocellular carcinoma.
AB  - BACKGROUND: Our previous cDNA array results indicated KIAA0101 as one of the
      differentially expressed genes in human hepatocellular carcinoma (HCC) as
      compared with non-cancerous liver. However, it is necessary to study its
      expression at protein level in HCC and its biological function for HCC cell
      growth. METHOD: Western blot and tissue array were performed to compare KIAA0101
      protein expression level in paired human HCC and non-cancerous liver tissues from
      the same patients. Investigation of its subcellular localization was done by
      using dual fluorescence image examination and enriched mitochondrial protein
      Western blot analysis. The in vitro cell growth curve was used for examining the
      effect of over-expression of KIAA0101 in HCC cells. FACS was used to analyze the
      cell cycle pattern in KIAA0101 expression positive (+) and negative (-) cell
      populations isolated by the pMACSKKII system after KIAA0101 cDNA transfection.
      RESULTS: Western blot showed KIAA0101 protein expression was down-regulated in
      HCC tissues as compared with their counterpart non-cancerous liver tissues in 25
      out of 30 cases. Tissue array also demonstrated the same pattern in 161 paired
      samples. KIAA0101 was predominantly localized in mitochondria and partially in
      nuclei. KIAA0101 cDNA transfection could inhibit the HCC cell growth in vitro. In
      cell cycle analysis, it could arrest cells at the G1 to S phase transition.
      CONCLUSION: KIAA0101 protein expression was down-regulated in HCC. This gene
      could inhibit the HCC cell growth in vitro and presumably by its blocking effect
      on cell cycle.

PMID- 16646991
TI  - Water quality and immatures of the M and S forms of Anopheles gambiae s.s. and
      An. arabiensis in a Malian village.
AB  - INTRODUCTION: The associations between the immatures of Anopheles gambiae s.s.
      (Diptera: Culicidae), its M and S forms, and Anopheles arabiensis among and
      within larval breeding habitats in Banambani, Mali were investigated under
      varying conditions of water quality and rainfall. The intent was to elucidate on
      niche partitioning of these taxa. METHODS: Immatures of An. arabiensis, An.
      gambiae s.s., and its M and S forms were sampled every alternate day for a month
      in mid-rainy season from three sampling sites in each of the larval breeding
      habitats (rock pools, swamp, and puddles). Water quality was characterized by
      alkalinity, conductivity, dissolved oxygen (D.O.), nitrate, orthophosphate, pH,
      temperature, total dissolved solids (TDS), and turbidity. A type 3 analysis of
      the GENMOD model was used to examine the associations between the proportional
      frequencies of young (first and second instar larvae) and old (third and fourth
      instar larvae and pupae) or total immatures of species or forms among sampling
      sites within and among larval breeding habitats during a category of rainfall as
      influenced by water quality. RESULTS: Of the 4,174 immatures sampled, 1,300 were
      molecularly identified to species and forms. Significant association between the
      proportional frequencies of young larvae of An. arabiensis, An. gambiae s.s., its
      M and S forms was found among sampling sites within habitats but not among larval
      breeding habitats. The proportional frequencies of young larvae of M and S forms
      varied daily perhaps due to recruitment, mortality, and dispersal within
      habitats. Conductivity and TDS had significant effects when the proportional
      frequencies of young larvae of M and S forms among sampling sites within habitats
      were significantly associated. Alkalinity, D.O., orthophosphate, pH, nitrate,
      temperature and turbidity had no effects on niche partitioning of species and
      forms among sampling sites within habitats. Rainfall did not affect the
      frequencies of these immatures. CONCLUSION: Conductivity and TDS have significant
      effects on niche partitioning of young larvae of M and S forms among sampling
      sites within habitats in Banambani, Mali.

PMID- 16646992
TI  - Screening chest radiography: results from a Greek cross-sectional survey.
AB  - BACKGROUND: Public health authorities worldwide discourage the use of chest
      radiography as a screening modality, as the diagnostic performance of chest
      radiography does not justify its application for screening and may even be
      harmful, since people with false positive results may experience anxiety and
      concern. Despite the accumulated evidence, various reports suggest that primary
      care physicians throughout the world still prescribe chest radiography for
      screening. We therefore set out to index the use of chest radiography for
      screening purposes among the healthy adult population and to analyze its
      relationship with possible trigger factors. METHODS: The study was designed as a
      cross-sectional survey. Five thousand four hundred and ninety-nine healthy
      adults, coming from 26 Greek provinces were surveyed for screening practice
      habits in the nationwide anticancer study. Data were obtained for the use of
      screening chest radiography. Impact of age, gender, tobacco exposure, family
      history positive for malignancies and professional-risk for lung diseases was
      further analyzed. RESULTS: we found that 20% (n = 1099) of the surveyed
      individuals underwent chest radiography for screening purposes for at least one
      time during the previous three years. Among those, 24% do so with a frequency
      equal or higher than once yearly, and 48% with a frequency equal or higher than
      every three years. Screening for chest radiography was more commonly adopted
      among males (OR 1.130, 95% CI 0.988-1.292), pensioners (OR 1.319, CI 1.093-1.593)
      and individuals with a positive family history for lung cancer (OR 1.251, CI
      0.988-1.583). Multivariate analysis confirmed these results. CONCLUSION: Despite
      formal recommendations, chest radiography for screening purposes was a common
      practice among the analyzed sample of Greek adults. This practice is of
      questionable value since the positive predictive value of chest radiography is
      low. The implementation of even a relatively inexpensive imaging study on a
      national scale would greatly burden health economics and the workload of
      radiology departments.

PMID- 16646993
TI  - Exploring photosynthesis evolution by comparative analysis of metabolic networks
      between chloroplasts and photosynthetic bacteria.
AB  - BACKGROUND: Chloroplasts descended from cyanobacteria and have a drastically
      reduced genome following an endosymbiotic event. Many genes of the ancestral
      cyanobacterial genome have been transferred to the plant nuclear genome by
      horizontal gene transfer. However, a selective set of metabolism pathways is
      maintained in chloroplasts using both chloroplast genome encoded and nuclear
      genome encoded enzymes. As an organelle specialized for carrying out
      photosynthesis, does the chloroplast metabolic network have properties adapted
      for higher efficiency of photosynthesis? We compared metabolic network properties
      of chloroplasts and prokaryotic photosynthetic organisms, mostly cyanobacteria,
      based on metabolic maps derived from genome data to identify features of
      chloroplast network properties that are different from cyanobacteria and to
      analyze possible functional significance of those features. RESULTS: The
      properties of the entire metabolic network and the sub-network that consists of
      reactions directly connected to the Calvin Cycle have been analyzed using
      hypergraph representation. Results showed that the whole metabolic networks in
      chloroplast and cyanobacteria both possess small-world network properties.
      Although the number of compounds and reactions in chloroplasts is less than that
      in cyanobacteria, the chloroplast's metabolic network has longer average path
      length, a larger diameter, and is Calvin Cycle -centered, indicating an overall
      less-dense network structure with specific and local high density areas in
      chloroplasts. Moreover, chloroplast metabolic network exhibits a better modular
      organization than cyanobacterial ones. Enzymes involved in the same metabolic
      processes tend to cluster into the same module in chloroplasts. CONCLUSION: In
      summary, the differences in metabolic network properties may reflect the
      evolutionary changes during endosymbiosis that led to the improvement of the
      photosynthesis efficiency in higher plants. Our findings are consistent with the
      notion that since the light energy absorption, transfer and conversion is highly
      efficient even in photosynthetic bacteria, the further improvements in
      photosynthetic efficiency in higher plants may rely on changes in metabolic
      network properties.

PMID- 16646994
TI  - [Comparison between coproparasitological techniques for the diagnosis of helminth
      eggs or protozoa oocysts in dogs].
AB  - In this study we evaluated the frequency of enteroparasites in pet dogs and their
      association with age, sex and breed, as well as the efficiency of the Willis
      Mollay, Faust, Sedimentation and Direct exam methods. By these methods we
      processed 401 fecal samples. The samples were positive in the following
      percentages: Ancylostoma spp. (53.1%), Toxocara canis (20.7%), Cystoisospora
      ohioensis (15.7%), Trichuris vulpis (3.7%), Dipylidium caninum (2.5%) and Taenia
      spp. (1.0%). Toxocara canis (67.3%) and C. ohioensis (47.3%) showed higher
      positivity in the puppies. The Willis-Mollay technique was more efficient in the
      diagnosis of Ancylostoma spp. and T. canis eggs. The Direct method was the least
      efficient. It was found that the majority of the cases of D. caninum were
      diagnosed by the Sedimentation method (8=2.0%), while for T. vulpis Willis-Mollay
      (12=3.0%) and Sedimentation (13=3.2%) were more efficient. In view of these
      results, we can recommend the association of Willis-Mollay and Sedimentation
      methods for the diagnosis of gastrointestinal helminths. Due to the elevated
      occurrence of Ancylostoma spp. and T. canis, which are involved in zoonotic
      diseases, it becomes necessary to apply more efficient prophylaxis of canine
      intestinal parasitosis at the City of Aracatuba, state of Sao Paulo.

PMID- 16646995
TI  - [Morphology and biometry of eggs and larvae of Strongyloides sp. Grassi, 1879
      (Rhabditoidea: Strongyloididae), a gastrointestinal parasite of Hydrochaeris
      hydrochaeris (Linnaeus, 1766) (Rodentia: Hydrochaeridae), in the municipality of
      Juiz de Fora, Minas Gerais, Brazil].
AB  - An important method to diagnose and study the helminthofauna of wild animals is
      to examine the host's feces to find eggs and larvae, seeking to identify the
      parasites and study their morphobiology. The objective of the present work is to
      provide morphological and biometric data on the eggs and larvae of Strongyloides
      sp., a capybara gastrointestinal parasite. Using the technique of Gordon and
      Whitlock, simple flotation and the modified Baermann examination, capybara fecal
      samples were selected based on a criterion of the highest proportion of eggs and
      larvae in the initial development stages, for morphometric description of eggs,
      L1, L2 and L3 of Strongyloides sp. From past reports of parasitism in
      Hydrochaeris hydrochaeris, we suspect that the eggs and larvae in this study are
      of Strongyloides chapini Sandground, 1925, which constitutes the first
      description of these stages for this species of nematode. Nevertheless, the
      morphology and biometry data of these stages demonstrate that they are similar to
      those of other species of the Strongyloides genus.

PMID- 16646996
TI  - [Evaluation of ectoparasites and hemoparasites in dogs kept in apartments and
      houses with yards in the city of Juiz de Fora, Minas Gerais, Brazil].
AB  - Fleas and ticks transmit various pathogens while feeding on the blood of dogs.
      This study sought to verify the occurrence of ectoparasitism and hemoparasitism
      in dogs from two urban areas in the city of Juiz de Fora, Minas Gerais, Brazil.
      Between February and August 2003, 101 dogs were studied: 50 came from apartments
      in the downtown region and 51 from houses with grassy yards. The ectoparasites
      were collected and conserved in etanol 70%. The occurrence of hemoparasites was
      verified by examining blood smears from sample taken from the dogs'ears. The
      blood smears were stained with Giemsa and 100 fields per slide were examined,
      studying the erythrocytes to determine parasitism. From among the dogs living in
      apartments, we found (with respective prevalence and mean intensity):
      Ctenocephalides felis (12%), (3.3+/-2.0); Rhipicephalus sanguineus (2%); and
      ixodid nymphs (2%). In this environment in the dogs were not found hemoparasites.
      From the houses with grassy yards, we observed the following prevalence levels
      and mean intensities: C. felis (14%), (2.28+/-1.9); R. sanguineus (35%), (7.8+/
      9.8); ixodid nymph (18%), (1.4+/-0.7); and ixodid larvae (4%), (12+/-14.4). The
      hemoparasites found were: Ehrlichia canis (16%) and Babesia canis (2%).

PMID- 16646997
TI  - [The effect of immersion in distilled water on the engorged larvae and nymphs of
      Amblyomma dubitatum Neumann, 1899 (Acari: Ixodidae)].
AB  - To evaluate the effect of the immersion of engorged larvae and nymphs of
      Amblyomma dubitatum experimentally fed on rabbits, the ticks were collected and
      formed control groups, without immersion, and groups witch were immersed by 24,
      48, 72, 96 hours and, for engorged larvaes, by eight weeks, in test tubes
      containing distilled water. During all experiment ticks were kept at 27 +/- 1
      degrees C, 80 +/- 10% RU and scotophase The parameters evaluated were: pre
      ecdysis, ecdysis and moulting periods; and ecdysis and mortality percentages.
      When compared with the control group, the effect (p<0,05) of immersion varied
      intra and inter stages. Apparently, immersion was less deleterious to A.
      dubitatum in comparison with A. cajennense and R. sanguineus from neotropical
      region, thus reflecting a long host relations with the capybara, its primary
      host.

PMID- 16646998
TI  - Efficacy of homeopathic treatment against natural infection of sheep by
      gastrointestinal nematodes.
AB  - The efficacy of the homeopathic treatment with the Fator Vermes, administered
      according to the manufacturer's recommendations, was evaluated against
      gastrointestinal nematodes infections in sheep. The experiment was divided into
      two phases: in the first phase (January/06/2004 to April/30/2004), the animals of
      the treated (n=10) and control (n=10) groups were treated individually with
      conventional anthelmintics to avoid deaths. In the second phase (April/30/2004 to
      July/06/2004), the sheep from the group that received the Fator Vermes were
      treated as they had been in the previous phase, while the control group animals
      were treated with conventional anthelmintics at 14 day intervals. In the first
      phase of the experiment, there was no significant difference (P>0.05) between
      group means regarding egg counts in feces (EPG), weight gain, or packed cell
      volume (PCV). Meanwhile, in the second phase, the control group sheep had a
      significantly higher weight gain, higher PCV values, and lower EPG counts.
      Infective larvae of Haemonchus spp., Trichostrongylus spp., Cooperia spp., and
      Oesophagostomum spp. were identified in the fecal cultures. After six months of
      daily treatment with the Fator Vermes, it was not possible to substantiate the
      product's benefits in both sheep health and productivity or in the prophylaxis of
      gastrointestinal nematode infections.

PMID- 16646999
TI  - [Species of the genus Eimeria (Apicomplexa: Eimeriidae) in giant anteaters
      (Myrmecophaga tridactyla Linnaeus, 1758) in captivity].
AB  - The parasitism of the two giant anteaters adults (Myrmecophaga tridactyla), one
      male and one female, infected naturally with Eimeria escomeli, E. tamanduae e E.
      marajoensis was related in the present research. In E. escomeli oocysts were 23.9
      +/- 1.89 by 19.7 +/- 1.60 microm and its sporocysts were 11.47 +/- 1.25 by 6.48
      +/- 0.80 microm. In E. tamanduae oocysts were 23.52 +/- 0.95 by 20.59 +/- 0.92
      microm and its sporocysts were 12.19 +/- 0.65 by 7.15 +/- 0.55 microm. In E.
      marajoensis oocysts were 13.5 +/- 1.7 by 13.1 +/- 1.8 microm and its sporocysts
      were 7.4 +/- 0.58 by 5.4 +/- 0.8 microm. Eimeria escomeli was described before
      parasitizing giants anteater from Bolivia, and it was point out as the first time
      in Brazil. The presence of E. tamanduae and E. marajoensis parasitizing giant
      anteaters indicate the possibility of having co-infection of them among animals
      of the family Myrmecophagidae.

PMID- 16647000
TI  - [Toxoplasma gondii in brains of pigs commercialized at the Municipality of Campos
      dos Goytacazes in the State of Rio de Janeiro, Brazil].
AB  - Brain samples of 12 pigs commercialized for food consumption at the Municipality
      of Campos dos Goytacazes in the State of Rio de Janeiro were examined for the
      presence of Toxoplasma gondii. Brain sample of each pig was grinded and submitted
      to peptic digestion. One ml of the homogenate of each sample was inoculated in
      three albino mice, and this procedure was repeated 24 hours later. Inoculated
      mice were observed during six weeks. Dead mice or those that presented clinical
      signs suggestive of the disease, were examined for the presence of tachyzoites in
      peritoneal exudates or tissue cysts in their brains. The percentage of positives
      brains was 50%, which is a confirmation that pigs could be considered as a
      potential source of infection of T. gondii for humans at this Municipality.

PMID- 16647001
TI  - [Alcoholic extract of lemongrass (Cymbopogon citratus) on the control of
      Boophilus microplus in cattle].
AB  - The objective of this study was to determine the effect of lemongrass (Cymbopogon
      citratus) alcoholic extracts on the control of Boophilus microplus in naturally
      infested Holstein cows. Twelve animals were allocated in three groups of four
      animals. Group 1 was treated with amitraz at 0.025%, Group 2 was treated with
      lemongrass extracts at 1.36% and Group 3 with the same product at 2.72% of the
      plant. Engorged ticks were evaluated on animals with length superior to 4.0 mm,
      before (mean of days -3, -2, -1) and at 1, 2, 3, 4, 5, 6, 7 and 14 days after
      treatment. The mean efficacy of amitraz was 97.93%. Lemongrass extract at 2.72%
      reduced tick infestation by 40.3, 46.6 and 41.5% on day 3, 7 and 14 post
      treatment, respectively.

PMID- 16647002
TI  - [Infestation with Linognathus africanus (Kellogg e Paine, 1911) (Linognathidae)
      and Bovicola caprae (Ewing, 1936) (Trichodectidae) in goat flock of the State of
      Rio de Janeiro, Brazil].
AB  - Mixed infestations with Linognathus africanus and Bovicola caprae were diagnosed
      in a lot of 20 goats from a flock of 40, belonging to a farm from the
      Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, RJ (22 degrees
      44'38''S and 43 degrees 42'27''W). Animals were of both sexes, varied ages and
      different breeds (half blood Saanen/Boer, Saanen, cross breeds), were examined in
      April of 2004. With an exception of one goat, parasitized only by L. africanus,
      the remainders 19 (95%) were infested by the two species lice. Of 69 (71%)
      specimens of L. africanus and 28 (28.9%) of B. caprae collected the ratio
      female:male for L. africanus were 4.6 (23:5), while for B. caprae were 4.8
      (57:12). The absence of L. africanus in recent surveys carried out in the semi
      arid regions of the Northeast Brazil where more the 60% of examined goats were
      parasitized by B. caprae suggests that the adaptation to the climatic variation
      might be different for the two species.

PMID- 16647003
TI  - [Review of 2005 revised international guidelines for cardiopulmonary
      resuscitation--concerning the problems of CPR in China].

PMID- 16647004
TI  - [Clinical studies on level of N-terminal portion of brain natriuretic in the
      treatment and prognosis of Chinese patients with chronic left heart failure].
AB  - OBJECTIVE: To study the relationship of the level of N-terminal portion of brain
      natriuretic (NT-ProBNP) with the treatment and prognosis of patients with acute
      attack of chronic left heart failure. METHODS: Patients (age range 18-80 years)
      with decompensated heart failure treated in the emergency department in Fuwai
      Hospital were included in this study. Dynamic changes of plasma levels of NT
      ProBNP, angiotensin (AO), renin activity (PRA), angiotensin II (AT II) and
      aldosterone (ALD) were detected by enzyme linked immunoadsorbent assay (ELISA)
      before anti-cardiac failure treatment and 3-5, 5-7 days after the treatment. All
      enrolled patients were followed up for 2 years after leaving hospital, and
      cardiovascular events such as death, myocardial infarction, worsening of heart
      failure, severe arrhythmia or delayed discharge from hospital were recorded.
      RESULTS: Compared with baseline level at admission, plasma NT-ProBNP levels were
      lowered on 3rd -5th day and 5th-7th day after admission and treatment (both
      P<0.05) in 44 patients with chronic left heart failure, but there was no
      difference in NT-ProBNP levels between the 3rd-5th and 5th -7th day after
      treatment. The levels of plasma NT-ProBNP increased much higher at all
      observation times in patients with cardiovascular events than without the events
      (all P<0.05), but the changes in AO, PRA, ATII and ALD showed no significant
      difference between two groups (all P>0.05). CONCLUSION: During acute onset,
      plasma NT-ProBNP levels in patients with chronic left heart failure can be
      lowered at 3-7 days after admission and treatment. Higher baseline levels of
      plasma NT-ProBNP may have certain predictive values for long term prognosis in
      patients with chronic left heart failure.

PMID- 16647006
TI  - [Changes of hemodynamics during establishment of animal model of acute myocardial
      infarction induced by ligation of left coronary artery in goat].
AB  - OBJECTIVE: To study the changes in hemodynamics in experimental acute myocardial
      infarction induced by ligation of the left coronary artery in goat. METHODS:
      Animal model of acute myocardial infarction was reproduced in 20 goats by
      ligation of the left coronary artery through xyphoid process. ST segment of
      electrocardiogram (ECG), mean artery blood pressure (MAP), central venous
      pressure (CVP), and heart rate (HR) were observed before, immediately, 30
      minutes, 1 hour and 2 hours after ligation of the left coronary artery. RESULTS:
      ECG of all goats was normal before operation. Immediately and 30 minutes after
      ligation, elevation of ST-segment was seen in 8 and 10 goats respectively, and in
      18 goats elevation of ST-segment was observed 2 hours after ligation. Four weeks
      after the operation, pathological Q wave was shown in the chest leads of ECG in
      18 goats. There was no significant difference in MAP, CVP and HR between before
      and after ligation. Frequent ventricular premature beats were found in 6 goats,
      but they were stopped after intravenous infusion of lidocaine. CONCLUSION: Small
      area of experimental acute myocardial infarction in goats shows slight effect on
      hemodynamics, though the production of myocardial infarction is reliable, and the
      life of the goats could be maintained for a long time after the ligation of the
      left coronary artery. The experiment provides a valuable animal model for the
      study of coronary heart disease.

PMID- 16647007
TI  - [Changes in substance P in myocardium and dorsal root ganglion following coronary
      artery occlusion in rats].
AB  - OBJECTIVE: To observe the changes in substance P in myocardium and dorsal root
      ganglion (DRG) following ligation of the left anterior descending branch of
      coronary artery. The substance P is commonly considered released mainly from
      afferent nerve fibers under noxious stimulation and could induce neurogenic
      inflammation in peripheral tissue. METHODS: Twenty-four adult male Sprague-Dawley
      rats, weighing 270-300 g, were randomly divided into four groups: sham-operated
      group, coronary artery occlusion (CAO) 1 hour group, CAO 3 hours group and CAO 6
      hours group, and 6 animals were in each group. The left anterior descending
      branch of coronary artery was occluded to establish the acute myocardial ischemia
      model except in the sham-operated group. The myocardium in ischemic and non
      ischemic (the contralateral side of ischemic myocardium) region and DRG were
      harvested as scheduled and processed for immunohistochemistry and for substance P
      mRNA semi-quantitative examination using reverse transcription-polymerase chain
      reaction (RT-PCR) technique. RESULTS: (1) substance P and substance P mRNA levels
      in myocardium of ischemic areas and myocardium of non-ischemic areas were
      significantly elevated after CAO compared with sham-operated group (all P<0.05),
      and they were highest in rats of CAO 3 hours group (all P<0.05). In the
      myocardium of non-ischemic areas, substance P and substance P mRNA levels were
      lower than those in myocardium of ischemic areas in CAO groups (all P<0.05). (2)
      substance P mRNA levels in DRG were significantly elevated after CAO compared
      with sham-operated group (all P<0.05), and were highest in rats of CAO 3 hours
      group (both P<0.05). CONCLUSION: CAO could evoke an increase in substance P in
      entire myocardium and substance P mRNA expression in DRG in rats, and the results
      might imply that neurogenic mechanism participates in the pathophysiological
      changes following myocardial ischemia.

PMID- 16647008
TI  - [Protective effects of dexamethasone on myocardium in rats with sepsis].
AB  - OBJECTIVE: To investigate the changes in heart function and myocardial mechanics
      in murine sepsis model, and the mechanism of the protective effect of
      dexamethasone on heart. METHODS: Wistar rats were randomly divided into control
      group, lipopolysaccharide (LPS) group (4 mg/kg LPS intravenously),
      LPS+dexamethasone group (4 mg/kg LPS+2 mg/kg dexamethasone intravenously), with
      32 rats in each group. A catheter was passed through right common carotid artery
      to the left cardiac ventricle. Function of the left ventricle was monitored, and
      blood was drawn at 0, 2, 4, 6 hours to detect concentrations of tumor necrosis
      factor-alpha (TNF-alpha), troponin T (TnT), with 8 rats for each time point.
      RESULTS: In sepsis rats, TnT increased significantly and could be lowered by
      dexamethasone [at 6 hours after the treatment (1.76+/-0.57) microg/L vs. (0.70+/
      0.36) microg/L, P<0.01]. There were changes in left ventricular peak systolic
      pressure (LVPP) and maximum rate of intraventricular pressure rise/down (+/-dp/dt
      max) to certain extent, and increase in left ventricular end-diastolic pressure
      (LVEDP), but these changes could be ameliorated by using dexamethasone. TNF-alpha
      increased significantly in sepsis rats, but dexamethasone could lower its level
      [at 2 hours after the treatment (11.22+/-2.38) pmol/L vs. (7.62+/-3.21) pmol/L,
      P<0.01]. CONCLUSION: Myocardium is remarkably damaged in rats with sepsis. TNF
      alpha could be regarded as one of the factors which could produce injury to
      myocardium. Dexamethasone could alleviate cardiac damage produced by endotoxin in
      sepsis model.

PMID- 16647010
TI  - [Comparative study on characteristics of congestive heart failure patients with
      preserved versus abnormal left ventricular systolic function and evaluation
      effects of therapy].
AB  - OBJECTIVE: To compare clinical characteristics and effects of therapy for
      hospitalized patients with congestive heart failure (CHF) and different left
      ventricular ejection fraction (LVEF) during hospitalization. METHODS: The medical
      records of 1 074 unselected consecutive patients with CHF who were admitted to
      Queen Mary Hospital from January, 2001 to January, 2002 were retrospectively
      reviewed. Three hundred and ninety-nine patients were categorized as having
      either normal left ventricular systolic function or systolic dysfunction based on
      the results of echocardiography. Clinical features with a slightly modified
      version of the Framingham criteria, laboratory results and drug therapies at
      discharge were compared. RESULTS: Among patients, the majority were women, 95.5%
      were > or =65 years and 50.6% > or =80 years of age. Classification of the
      severity of heart failure showed that 70.2% were New York Heart Association
      (NYHA) III and IV. Only 399 patients had borderline LVEF at the time of
      hospitalization, of these patients 191 (47.9%) had preserved systolic function
      (LVEF > or =0.50), and 208 (52.1%) with LVEF<0.50. Patients with LVEF > or =0.50,
      who tended to be elderly and more often female, exhibited a lower incidence of
      coronary artery disease and diabetes than patients with LVEF<0.50 (all P<0.05).
      Patients with preserved systolic function had a significantly higher prevalence
      of auricular fibrillation (P<0.05), accounting for up to 84 patients (44.0%) with
      it, and number of hospitalization for CHF increased. Among patients with systolic
      dysfunction, 22.6% were discharged on a therapeutic regimen of digoxin, 63.0% on
      an angiotensin-converting enzyme inhibitor (ACEI), and 12.0% on a beta-blocker,
      13.9% on a calcium channel blocker. These accounted for 62.3%, 35.1%, 9.4% and
      18.3% in patients with preserved systolic function, respectively. There was a
      higher incidence of use of digoxin (P<0.05). CONCLUSION: In hospitalized patients
      with heart failure, the clinical signs and symptoms of chronic heart failure are
      similar to those of patients with CHF, LVEF is a powerful prognostic predictor to
      distinguish CHF patients with normal systolic function from those with systolic
      dysfunction. Criteria for use of ACEI and beta-blocker are still not clear cut.
      It is important to differentiate CHF patients with LVEF<0.50 from that with LVEF>
      or =0.50 in order to achieve a better therapeutic result in the treatment of CHF.

PMID- 16647011
TI  - [Histopathology analysis of microemboli after thrombolysis].
AB  - OBJECTIVE: To observe the changes in fibrin of microemboli in micro-embolism soon
      after thrombolysis, in order to provide a theoretical basis for micro
      thrombolytic therapy. METHODS: Thirty adult male SD rats weighing (180+/-10)g
      were randomized into five groups: 5, 30, 60 and 90 minutes groups after micro
      thromboembolization and the control group. Rat cremasteric artery was embolized
      with photochemical method, and micro-thrombi were produced after thrombolysis by
      staphylokinase. The levels of tissue plasminogen activator (t-PA) and tissue
      plasminogen activator inhibitor (PAI) were immunohistochemically determined, and
      taken as the markers of fibrin dissolution. RESULTS: Fibrin was observed in
      pathologic sections as well as fibrinolytic markers t-PA and PAI in
      immunohistochemical sections. The levels of t-PA were found to be reduced while
      that of PAI increased gradually with passage of time. CONCLUSION: Fibrin is one
      of the main constituents of microthrombi soon after thrombolysis. The content of
      fibrous emboli increases after microembolization with the passage of time.
      Thrombolysis plays an important role in the treatment of "no reflow phenomenon".

PMID- 16647012
TI  - [Aspirin resistance in patients taking small dose of aspirin].
AB  - OBJECTIVE: To investigate the phenomenon and influencing factors of aspirin
      resistance (AR) in patients taking small dose of aspirin. METHODS: Three hundred
      and twenty-eight patients with stable cardiac and cerebral vascular diseases,
      diabetes mellitus, et al taking aspirin 100 mg/d for > or =14 days, and then
      their blood samples were collected for determination of optical platelet
      aggregation index using arachidonic acid (AA) and adenosine diphosphate (ADP). AR
      was defined as a state in which aggregation of > or =20% with AA and that > or
      =70% with ADP was found. Aspirin semi-resistance (ASR) was defined as meeting one
      of the above criteria. If both above criteria were not met, the condition was
      defined as aspirin sensitive. The difference in clinical characteristics among
      the groups and independent risk factors associated with AR and ASR were analyzed.
      RESULTS: Of 328 patients, 4.9% were AR, 27.4% were ASR. Among AR+ASR group,
      female, elderly, diabetic and hypertensive patients were predominant, but less
      common in smokers. Logistic regression analysis showed that diabetes mellitus was
      an independent risk factor of AR and ASR [odds ratio (OR)=0.953, 95% confidence
      interval (CI) 0.323-0.876, P=0.013], and hypertension was independently
      associated with AR and ASR (OR=0.610, 95%CI 0.376-0.991, P=0.046). The risk of AR
      and ASR was increased in non-smokers (OR=2.231, 95%CI 1.182-4.210, P=0.013).
      CONCLUSION: The incidence rate of AR in patients taking small dose of aspirin was
      4.9%. Diabetes mellitus and hypertension are relative risk factors of AR and ASR.
      The risk of AR and ASR in the no-smoking patients is increased.

PMID- 16647014
TI  - [Study on up-regulation of the expression of angiotensin-converting enzyme-2 in
      human umbilical vein endothelial cells by telmisartan].
AB  - OBJECTIVE: To investigate the effect of telmisartan on the protein and gene
      expression of angiotensin-converting enzyme-2 (ACE2) in human umbilical vein
      endothelial cells (HUVECs). METHODS: HUVECs were treated with various
      concentrations of telmisartan (10(-7), 10(-6) and 10(-5) mol/L) for 24 hours. In
      a time-control experiment, HUVECs were treated with telmisartan at the final
      concentration of 10(-6) mol/L for 6, 12 and 24 hours, respectively. In another
      experiment, HUVECs were treated with PD123319 (10(-6) mol/L) only or combined
      with same final concentration of telmisartan for 12 hours, respectively. Changes
      in both protein and gene expression of ACE2 were determined with Western blot
      analysis and reverse transcription-polymerase chain reaction (RT-PCR) technique,
      respectively. RESULTS: Telmisartan induced a concentration and time dependent
      increase in both protein and gene expression of ACE2 (P<0.05 or P<0.01). Compared
      with control group, treatment of HUVECs with telmisartan at the concentration of
      10(-7), 10(-6) and 10(-5) mol/L stimulated 1.5-, 2.7- and 4.6-fold increase in
      the ACE2 protein expression, as well as 1.2-, 2.3- and 4.5-fold increase in its
      gene expression, respectively. After treatment of HUVECs with telmisartan for 6,
      12, and 24 hours at the concentration of 10(-6) mol/L, the ACE2 protein
      expression increased 1.6-, 2.7- and 4.2-fold, and its gene expression increased
      1.3-, 2.3- and 4.0-fold, respectively. Compared with control and telmisartan
      groups, PD123319 had no effect on both protein and gene expression of ACE2
      (P>0.05). CONCLUSION: Telmisartan up-regulates the protein and gene expression of
      ACE2 in HUVECs in a concentration and time dependent manner. This effect may be
      mediated via its specific pathway.

PMID- 16647015
TI  - [Experimental study of effects of cyclooxygenase-2 inhibitor on apoptosis of
      hypoxic myocardial cells in vitro].
AB  - OBJECTIVE: To observe the effects of cyclooxygenase (COX)-2 inhibitor on
      apoptosis of hypoxic myocardial cells in vitro. METHODS: The myocardial cells
      were obtained from new-born Wistar rats, and were dispersed to single cell with
      trypsin. The cells in 4th-6th passages were randomly divided into 24 samples
      (every sample contained 1 x 10(5) cells): normal control group, hypoxic
      myocardial cells control group; hypoxic myocardial cells+NS-398 (20 micromol/L)
      and hypoxic myocardial cells+aspirin (100 microg/L). During culture, oxygen was
      replaced by N(2), and the cells were cultivated in 5% CO(2)+95% N(2) at 37
      centigrade for 6 hours. Either interventional medicine or same amount of dimethyl
      sulphoxide was added to the cells 30 minutes before hypoxia. The expression of
      COX-1 and COX-2 in cultured myocardial cells in vitro was examined with Western
      blot. The apoptosis percentage of cells in each group was examined with flow
      cytometry. After centrifuging the culture medium under low temperature, 6-keto
      prostaglandin F(1alpha) (6-keto-PGF(1alpha)) and thromboxane B(2) (TXB(2)) were
      determined with radioimmunoassay (RIA). RESULTS: There was no significant
      difference in the expression of COX-1 among the groups. The expression of COX-2
      was higher in all acute hypoxic myocardial cells groups compared with the control
      group. Neither aspirin nor NS-392 inhibited the expression of COX-2. The positive
      percentage of apoptosis of cultured myocardial cells ranked as follow: hypoxic+NS
      398 group, hypoxic +aspirin group, hypoxic control group and normal control
      group. The differences of apoptosis rate between hypoxic+NS-398 group and other
      groups were significant (all P<0.05). The levels of TXB(2) in each group of cell
      medium ranked in the following order: normal control group, hypoxic +NS-398
      group, hypoxic+aspirin group and hypoxic control group. The difference of TXB(2)
      level between hypoxic+NS-398 group and hypoxic control group was
      significant(P<0.05). The levels of 6-keto-PGF(1alpha) in each culture medium
      ranked in the following order: normal control group, hypoxic+aspirin group,
      hypoxic+NS-398 group and hypoxic control group. The difference between hypoxic+NS
      398 group and hypoxic control group was significant (P<0.05). The ratio of
      TXB(2)/6-keto-PGF(1alpha) showed no significant difference (P>0.05) among groups.
      CONCLUSION: The results suggest that acute hypoxia could directly induce cultured
      myocardial cells to express COX-2, but do not effect expression of COX-1. Hypoxia
      could elevate the level of 6-keto-PGF(1alpha) and TXB(2) in culture medium. COX-2
      inhibitor (NS-398) could lessen the elevation, but it could not change the ratio
      between TXB(2) and 6-keto PGF(1alpha). NS-398 could increase apoptosis percentage
      of hypoxic myocardial cells in vitro, and the effect is independent of other
      inflammatory cells.

PMID- 16647016
TI  - [Relationship between interleukin-6 gene polymorphism and coronary heart disease
      and its effect on plasma lipid levels].
AB  - OBJECTIVE: To study the relationship between interleukin-6 (IL-6) gene promoter
      572 C/G and -634 C/G polymorphism and coronary heart disease (CHD) and the
      influence of IL-6 gene polymorphism on plasma lipid and lipoprotein levels.
      METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) was used for the detection of IL-6 genotype in 165 patients with CHD and
      170 healthy persons. The plasma lipid and lipoprotein levels were measured by
      routine method. RESULTS: Plasma total cholesterol (TC), triglyceride (TG) and low
      density lipoprotein cholesterol (LDL-C) of the patients with CHD were
      significantly higher than those of the controls (all P<0.05). The distributions
      of IL-6 gene -634 C/G polymorphism were not different between CHD group and
      control group (P>0.05), but the IL-6 gene-572 C/G polymorphism was significantly
      different between them (P<0.05). The relative risk of CHD of C allele was 1.652
      times to the G allele [odds ratio (OR)=1.652, 95% confidence interval (CI): 1.137
      2.401]. The level of plasma lipid in G allele carriers was significantly higher
      than non-carriers (P<0.05). CONCLUSION: IL-6 gene -572 C/G polymorphism is
      associated with CHD, and G allele is an important genetic marker. IL-6 gene
      polymorphism may affect CHD through elevation of plasma lipid and lipoprotein
      levels.

PMID- 16647017
TI  - [Levels of plasma interleukin-18 and interferon-gamma in patients with coronary
      heart disease].
AB  - OBJECTIVE: To investigate the role of interleukin-18 (IL-18) and interferon-gamma
      (IFN-gamma) in coronary heart disease (CHD). METHODS: The levels of plasma IL-18
      and IFN-gamma in 45 patients with CHD and 30 normal volunteers were determined by
      enzyme linked immunoadsorbent assay (ELISA). The correlation between the levels
      of these two cytokines and the relationship between their levels and the state of
      CHD were analyzed. RESULTS: The plasma levels of IL-18 and IFN-gamma in patients
      with CHD were increased significantly when compared to those in normal controls
      [IL-18: (373.6+/-176.7) ng/L vs. (226.3+/-88.9) ng/L, P<0.01; IFN-gamma: (1.769+/
      0.087) ng/L vs. (0.087+/-0.038) ng/L, P<0.01]. The two cytokines were positively
      correlated significantly (r=0.788, P<0.01)]. The plasma levels of IL-18 and IFN
      gamma were significantly different in different states of CHD, and they increased
      with the aggravation of CHD respectively (all P<0.01). Moreover, the plasma
      levels of IL-18 and IFN-gamma in patients complicated with heart failure (HF)
      were higher than those not complicated with HF, respectively (all P<0.01).
      CONCLUSION: The findings suggest that IL-18 and IFN-gamma may participate in the
      pathogenesis and progression of CHD. The plasma levels of two cytokines may be
      used as parameters of estimation the morbid state of CHD.

PMID- 16647030
TI  - A novel icetexane diterpene, 5-epi-icetexone from Salvia gilliessi is active
      against Trypanosoma cruzi.
AB  - In this work the effect of a novel compound, 5-epi-icetexone (ICTX) obtained from
      Salvia gilliessi Benth. (Labiatae), is studied on cultured epimastigotes of
      Trypanosoma cruzi (Tulahuen). It was found that the compound exerts an
      antiproliferative effect on the parasites at concentrations between 2.8 and 4.2
      microM, and similar sensitivity in other strains (Dm28c, CL-Brener and Y-strain).
      The compound was deleterious at concentrations higher than 4.2 microM, with an
      estimated IC50 of 6.5+/-0.75 microM, but with low cytotoxicity to mammalian
      cells. These effects were irreversible, even at short times of exposure to the
      drug. In solution, ICTX showed to be stable for at least 96 h at 29 degrees C.
      With cytostatic dose a little percentage of parasites was resistant to the action
      of ICTX, and they continued growing although with different kinetic. By electron
      transmission microscopy, at dose of 4.2 microM an external vesiculization was
      observed on the first day of exposure to the compound, but the parasite cytoplasm
      became plenty of vacuoles and exhibited nuclear disorganization from the second
      day of exposure. It was concluded that ICTX is active against T. cruzi and may
      act by multiple mechanisms. In future, this novel icetexane diterpene may be a
      good candidate for therapeutic use against Chagas' disease.

PMID- 16647031
TI  - Amperometric determination of phosphoglucomutase activity with a bienzyme screen
      printed biosensor.

PMID- 16647032
TI  - An improved cloning strategy for chromatin-immunoprecipitation-derived DNA
      fragments.

PMID- 16647033
TI  - A biosensor-based approach toward purification and crystallization of G protein
      coupled receptors.
AB  - Biacore technology was used to develop an affinity purification method and screen
      cocrystallization conditions for the chemokine receptor CCR5. We characterized
      the binding of nine HIV gp120 variants and identified a truncated construct
      (YU2DV1V2) that bound CCR5 independent of CD4. This construct was used in an
      affinity purification step to improve the activity of detergent-solubilized
      receptor by approximately 300%. The biosensor was also used to screen receptor
      binding activity automatically under 50 different crystallization conditions. We
      found that high-molecular-weight polyethylene glycols (PEGs 4,000 and 8,000 Da)
      most often stabilized the receptor and improved complex formation with potential
      cocrystallization partners such as conformationally sensitive monoclonal
      antibodies and gp120. Our results show how biosensors can provide unique insights
      into receptor purification methods and reveal the effects of crystallization
      conditions on complex formation. Importantly, these methods can be readily
      applied to other systems.

PMID- 16647034
TI  - Fluorescent in-gel protein detection by regulating the pH during staining.

PMID- 16647035
TI  - A nonradioactive, cell-free method for measuring protein synthesis inhibition by
      Pseudomonas exotoxin.
AB  - Pseudomonas exotoxin A (PE) inhibits protein synthesis by NAD-dependent ADP
      ribosylation of eukaryotic elongation factor 2. Traditionally, toxin activity has
      been characterized, either in living cells or cell-free systems, using
      radioactive compounds for quantification. The increased costs of radioactive
      waste disposal together with heightened security concerns have made the use of
      radioactive isotopes less attractive for routine laboratory assays. We therefore
      adapted a cell-free rabbit reticulocyte in vitro transcription-translation system
      that utilizes a reporter (beta-galactosidase) to measure toxin activity. The
      assay for PE is rapid, scalable, log-linear, NAD dependent and can be used to
      assess the neutralizing activity of anti-PE antibody preparations.

PMID- 16647036
TI  - Hath1 up-regulates gastric mucin gene expression in gastric cells.
AB  - The Notch signaling pathway is known to mediate the differentiation and fate
      specification of cells in embryonic stage and adult tissues. Several tumors
      exhibit aberrant expression of Notch signaling component genes, such as
      Notch1/2/3 and Hath1. In this study, we investigated the mRNA expression of seven
      Notch-related genes, Notch1/2/3, Hes1/2/3, and Hath1, and then compared it with
      the expression of gastric mucin genes, MUC5AC and MUC6, in eight gastric cancer
      (GC) cell lines. Notch1/2/3 and Hes1 were expressed in most GC cell lines as well
      as normal gastric mucosae, while Hes2/3 were expressed in neither these cell
      lines nor the normal stomach. As for Hath1, five GC cell lines exhibited
      undetectable levels, while normal gastric mucosa expressed Hath1. The expression
      patterns of Hath1 and MUC6 were closely related in most GC cell lines. Many
      MUC5AC-positive cases also tended to show Hath1 expression. Over-expression of
      Math1, a mouse Hath1 homolog, in the GC cells strongly enhanced both the MUC6 and
      MUC5AC mRNA levels. Moreover, knockdown of Hath1 by means of RNA interference
      significantly decreased the expression of both mucin genes. These data indicate
      that Hath1 is one of the transcriptional regulators for MUC6 and MUC5AC in GC
      cells. It is also possible that loss of Hath1 expression may play a role in
      gastric carcinogenesis.

PMID- 16647037
TI  - Spotting and validation of a genome wide oligonucleotide chip with duplicate
      measurement of each gene.
AB  - The quality of DNA microarray based gene expression data relies on the
      reproducibility of several steps in a microarray experiment. We have developed a
      spotted genome wide microarray chip with oligonucleotides printed in duplicate in
      order to minimise undesirable biases, thereby optimising detection of true
      differential expression. The validation study design consisted of an assessment
      of the microarray chip performance using the MessageAmp and FairPlay labelling
      kits. Intraclass correlation coefficient (ICC) was used to demonstrate that
      MessageAmp was significantly more reproducible than FairPlay. Further
      examinations with MessageAmp revealed the applicability of the system. The linear
      range of the chips was three orders of magnitude, the precision was high, as 95%
      of measurements deviated less than 1.24-fold from the expected value, and the
      coefficient of variation for relative expression was 13.6%. Relative quantitation
      was more reproducible than absolute quantitation and substantial reduction of
      variance was attained with duplicate spotting. An analysis of variance (ANOVA)
      demonstrated no significant day-to-day variation.

PMID- 16647038
TI  - Carbohydrate microarrays reveal sulphation as a modulator of siglec binding.
AB  - Siglecs are receptors on cells of the immune, haemopoietic, and nervous systems
      that recognize sialyl-glycans with differing preferences for sialic acid linkage
      and oligosaccharide backbone sequence. We investigate here siglec binding using
      microarrays of Lewis(x) (Le(x))- and 3'-sialyl-Le(x)-related probes with
      different sulphation patterns. These include sulphation at position 3 of the
      terminal galactose of Le(x), position 6 of the galactose of Le(x) and sialyl
      Le(x), position 6 of N-acetylglucosamine of Le(x) and sialyl-Le(x), or both
      positions of sialyl-Le(x). Recombinant soluble forms of five siglecs have been
      investigated: human Siglec-7, -8, -9, and murine Siglec-F and CD22 (Siglec-2).
      Each siglec has a different binding pattern. Unlike two C-type lectins of
      leukocytes, L-selectin and Langerin, which also bind to sulphated analogues of
      sialyl-Le(x), the siglecs do not give detectable binding signals with sulphated
      analogues that are lacking sialic acid. The sulphate groups modulate, however,
      positively or negatively the siglec binding intensities to the sialyl-Le(x)
      sequence.

PMID- 16647039
TI  - Stability of membrane potential in heart mitochondria: single mitochondrion
      imaging.
AB  - Mitochondrial membrane potential (delta psi(m)) plays an important role in
      cellular activity. Although delta psi(m) of intracellular mitochondria are
      relatively stable, the recent experiments with isolated mitochondria demonstrate
      that individual mitochondria show frequent fluctuations of delta psi(m). The
      current study is performed to investigate the factors that stabilize delta psi(m)
      in cells by observing delta psi(m) of individual isolated mitochondria with
      fluorescence microscopy. Here, we report that (1) the transient depolarizations
      are also induced for mitochondria in plasma membrane permeabilized cells, (2)
      almost all mitochondria isolated from porcine hearts show the transient
      depolarizations that is enhanced with the net efflux of protons from the matrix
      to the intermembrane space, and (3) ATP and ADP significantly inhibit the
      transient depolarizations by plural mechanisms. These results suggest that the
      suppression of acute alkalinization of the matrix together with the presence of
      ATP and ADP contributes to the stabilization of delta psi(m) in cells.

PMID- 16647040
TI  - Genetics of subpeptin JM4-A and subpeptin JM4-B production by Bacillus subtilis
      JM4.
AB  - Subpeptin JM4-A and subpeptin JM4-B are two novel antimicrobial peptides produced
      by Bacillus subtilis JM4. To identify putative genes involved in their
      production, degenerate PCR primers targeted to conserved motifs of nonribosomal
      peptide synthetases (NRPSs) were used. A resulting 1.2 kb PCR product had high
      sequence similarity to genes of NRPSs, and then a 2.8 kb DNA fragment flanking it
      was cloned subsequently. Gene disruption of the resulting 4 kb DNA fragment
      produced subpeptin-deficient mutant, suggesting that subpeptin JM4-A and
      subpeptin JM4-B were biosynthesized by NRPSs. Based on this result, a 48 kb gene
      cluster was cloned, which consisted of nine coding sequences (CDSs) involved in
      antimicrobial peptide biosynthesis, regulation, and resistance. Disruption of two
      relatively large CDSs subA and subC led to subpeptin-deficient mutants, which
      supported the involvement of the cloned gene cluster in subpeptin biosynthesis.

PMID- 16647041
TI  - Caveolin-3-anchored microdomains at the rabbit sarcoplasmic reticulum membranes.
AB  - It is generally believed that sphingomyelin- and cholesterol-enriched
      microdomains can be isolated as detergent-resistant membranes (DRMs) from plasma
      membrane and organelle membranes. Here, we describe the isolation and
      characterization of microdomains from sarcoplasmic reticulum (SR) membranes.
      These SR-derived detergent-resistant membranes (SR-DRMs) enriched in
      sphingomyelin and cholesterol have a low buoyant density. Immunofluorescence
      microscopy of SR membranes shows the presence of caveolin-3 in the SR, known as a
      marker protein of caveolae at plasma membrane. We also demonstrated that
      significant amount of SERCAs together with caveolin-3 associates with SR-DRMs and
      are fully functional. Depletion of cholesterol caused the disruption of SR-DRMs.

PMID- 16647042
TI  - Curcumin potently blocks Kv1.4 potassium channels.
AB  - Curcumin, a major constituent of the spice turmeric, is a nutriceutical compound
      reported to possess therapeutic properties against a variety of diseases ranging
      from cancer to cystic fibrosis. In whole-cell patch-clamp experiments on bovine
      adrenal zona fasciculata (AZF) cells, curcumin reversibly inhibited the Kv1.4K+
      current with an IC50 of 4.4 microM and a Hill coefficient of 2.32. Inhibition by
      curcumin was significantly enhanced by repeated depolarization; however, this
      agent did not alter the voltage-dependence of steady-state inactivation. Kv1.4 is
      the first voltage-gated ion channel demonstrated to be inhibited by curcumin.
      Furthermore, these results identify curcumin as one of the most potent
      antagonists of these K+ channels identified thus far. It remains to be seen
      whether any of the therapeutic actions of curcumin might originate with its
      ability to inhibit Kv1.4 or other voltage-gated K+ channel.

PMID- 16647043
TI  - Identification and characterization of p49/STRAP as a novel GLUT4-binding
      protein.
AB  - To identify novel regulatory components involved in the recycling of the insulin
      responsive glucose transporter GLUT4, we have used the yeast two-hybrid system to
      isolate GLUT4-binding proteins from a rat adipose cell cDNA library. We found a
      49-kDa protein (p49/STRAP) that specifically interacts with an acidic amino acid
      motif (Q7IGSEDG) in the N-terminus of GLUT4. Confocal immunofluorescence
      microscopy of primary rat adipose cells shows co-localization of myc-p49 with
      GLUT4 and also with the ER-resident protein calnexin. Insulin stimulation had no
      effect on GLUT4-binding and subcellular distribution of p49 in adipose cells.
      However, overexpression of the GLUT4-binding domain of p49 in adipose cells
      reduces protein synthesis and cell-surface expression of GLUT4, but not of GLUT8.
      Moreover, cell-surface expression of a p49-binding-deficient GLUT4 mutant (ED/QN)
      is also reduced. Kinetic analysis of HA-epitope-tagged GLUT4 protein synthesis
      indicates a possible role of p49 in biosynthesis and/or processing of GLUT4 in
      adipose cells.

PMID- 16647044
TI  - Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition
      of the caspase-8-mediated apoptotic pathway.
AB  - We have previously shown that carbon monoxide (CO) (250 ppm) prevented tumor
      necrosis factor-alpha (TNFalpha)-induced apoptosis and activated the
      transcription factor NF-kappaB in hepatocytes both in vivo and in vitro. These
      studies were conducted to further determine the mechanisms by which CO suppresses
      apoptotic signaling in TNFalpha (10 ng/ml) and Actinomycin D (ActD, 200 ng/ml)
      treated hepatocytes. Consistent with our previous findings, CO protected against
      TNFalpha/ActD-induced cell death, which is in part dependent on NF-kappaB
      activation. This was associated with a reduction in mitochondrial damage, a
      decrease in cytochrome c release, and an inhibition of translocation of Bcl
      proteins to mitochondria. In conjugation with inhibition of these mitochondrial
      events, CO also suppressed caspases-8 and -3 cleavage in response to
      TNFalpha/ActD. Inhibition of NF-kappaB activation resulted in diminished CO
      induced cFLIP expression and increased caspase-8 cleavage from cells treated with
      TNFalpha/ActD. These data indicate that CO interferes with apoptotic signaling at
      a proximal step.

PMID- 16647045
TI  - Insights from modeling the 3D structure of H5N1 influenza virus neuraminidase and
      its binding interactions with ligands.
AB  - The highly pathogenic H5N1 influenza virus, which is rapidly mutating and
      becoming increasingly drug-resistant, was investigated by means of structure
      activity relationship between NA (neuraminidase) and three inhibitors, i.e., DANA
      (2,3-didehydro-2-deoxy-N-acetylneuraminic acid), zanamivir, and oseltamivir. A
      homology model of the H5N1-NA from the highly pathogenic chicken H5N1 A viruses
      isolated during the 2003-2004 influenza outbreaks in Japan was built based on the
      crystal structure of N9-NA complexed with DANA (PDB code: 1F8B). It was found
      that the traditional constituent residues around the active site of NA family are
      highly conserved in the H5N1-NA. However, a partially lipophilic pocket composed
      by Ala248 and Thr249 in N9-NA becomes a hydrophilic pocket because the two
      residues in the H5N1-NA are replaced by hydrophilic residues Ser227 and Asn228,
      respectively. On the other hand, two hydrophilic residues Asn347 and Asn348 in
      the N9-NA are replaced by two lipophilic residues Ala323 and Tyr324 in the H5N1
      NA, respectively, leading to the formation of a new lipophilic pocket. This kind
      of subtle variation not only destroys the original lipophilic environment but
      also changes the complement interaction between the H5N1-NA and DANA. Such a
      finding might provide insights into the secret why some of H5N1 strains bear high
      resistance for existing NA inhibitors, and stimulate new strategies for designing
      new drugs against these viruses.

PMID- 16647046
TI  - Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and
      glutamate levels in the nucleus accumbens of rats.
AB  - Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been
      reported that Ipt inhibited cocaine-induced dopamine and glutamate release,
      suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt
      blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a
      heterologously expressed SH-EP1 cell line and in native midbrain dopamine
      neurons. In the present study, we examined whether Ipt prevents nicotine-induced
      neurotransmitter release in the nucleus accumbens (NAc) using in vivo
      microdialysis methods in awake, freely moving rats. Ipt was administered through
      a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg,
      s.c.). The results show that acute nicotine treatment induced an increase of both
      dopamine and glutamate levels in the rat NAc, and that Ipt significantly
      attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt
      may serve as a novel compound to block nicotine-induced dopamine and glutamate
      release in the brain reward center, in turn decreasing nicotine reinforcement and
      dependence.

PMID- 16647047
TI  - Age-related changes in glutathione and glutathione-related enzymes in rat brain.
AB  - The most reliable and robust risk factor for some neurodegenerative diseases is
      aging. It has been proposed that processes of aging are associated with the
      generation of reactive oxygen species and a disturbance of glutathione
      homeostasis in the brain. Yet, aged animals have rarely been used to model the
      diseases that are considered to be age-related such as Parkinson's or Alzheimer's
      disease. This suggests that the results from these studies would be more valuable
      if aged animals were used. The present study was designed to provide insight into
      the glutathione redox state in young and aged rat siblings of both genders by
      studying the enzyme activities related to glutathione synthesis, cycling, and
      usage. The results suggested a significant age-related reduction of reduced
      glutathione (GSH) level in all brain regions examined, associated with an
      increase of GSH oxidation to glutathione disulfide (GSSG) and decrease of the
      GSH/GSSG ratio. These changes were accompanied by diminished gamma
      glutamylcysteine synthetase activity in de novo glutathione synthesis and
      increased lipid peroxidation. In addition, these changes were associated with
      increased enzyme activities related to the GSH usage (glutathione peroxidase,
      gamma-glutamyl transpeptidase, and glutathione S-transferase). The results
      indicate that aged animals are likely more vulnerable to oxidative stress and
      insinuate the roles of aged animals in modeling age-related neurodegeneration
      diseases.

PMID- 16647048
TI  - Characterization of Gpr101 expression and G-protein coupling selectivity.
AB  - This report describes the identification and characterization of the murine
      orphan GPCR, Gpr101. Both human and murine genes were localized to chromosome X.
      Similar to its human ortholog, murine Gpr101 mRNA was detected predominantly in
      the brain within discrete nuclei. A knowledge-restricted hidden Markov model
      based algorithm, capable of accurately predicting G-protein coupling selectivity,
      indicated that both human and murine GPR101 were likely coupled to Gs. This
      prediction was supported by the elevation of cyclic AMP levels and the activation
      of a cyclic AMP response element-luciferase reporter gene in HEK293 cells over
      expressing human GPR101. Consistent with this, over-expression of human GPR101 in
      a yeast-based system yielded an elevated, agonist-independent reporter gene
      response in the presence of a yeast chimeric Galphas protein. These results
      indicate that GPR101 participates in a potentially wide range of activities in
      the CNS via modulation of cAMP levels.

PMID- 16647049
TI  - The role of rafts in the fibrillization and aggregation of prions.
AB  - A key molecular event in prion diseases is the conversion of the prion protein
      (PrP) from its normal cellular form (PrP(C)) to the disease-specific form
      (PrP(Sc)). The transition from PrP(C) to PrP(Sc) involves a major conformational
      change, resulting in amorphous aggregates and/or fibrillar amyloid deposits. Here
      several lines of evidence implicating membranes in the conversion of PrP are
      reviewed with a particular emphasis on the role of lipid rafts in the
      conformational transition of prion proteins. New correlations between in vitro
      biophysical studies and findings from cell biology work on the role of rafts in
      prion conversion are highlighted and a mechanism for the role of rafts in prion
      conversion is proposed.

PMID- 16647050
TI  - Effectiveness of a tris-based extender (SHOTOR diluent) for the preservation of
      Bactrian camel (Camelus bactrianus) semen.
AB  - The development of a suitable semen extender is required to extend artificial
      breeding programs and to preserve the genetic potential of Bactrian camel.
      Experiments were conducted to provide the optimal osmolality and pH of tris-based
      extender and to compare that with available extenders for short-term preservation
      of Bactrian camel semen at 4 degrees C during 24 h. In experiments I and II, the
      effects of varying osmolalities (270, 300, 330, 360, and 390 mOsm/kg) and pHs
      (5.5, 6, 6.9, 7.5, 7.9, and 8.9) of tris-based extender on sperm viability were
      investigated. In experiment III, the efficiency of tris-based extender (SHOTOR
      diluent) in preserving Bactrian camel semen was compared with lactose (10%),
      sucrose (10%) and Green buffer. Viability parameters including progressive
      forward motility (PFM), plasma membrane integrity and the percentage of live
      spermatozoa were assessed. The data were analyzed using general linear model
      procedure. In the majority of assessments using tris-based extender, the
      viability of spermatozoa was superior at the osmolality of 330 mOsm/kg and pH of
      6.9. PFM was significantly greater at the time of semen dilution in tris-based
      (65.5%) and Green buffer (60.5%) compared to that of lactose (31%) and sucrose
      (28%) extenders (P<0.05), and remained elevated throughout the experiment. There
      was no significant difference in other viability parameters among 4 extenders
      (P>0.05). In conclusion, the utilization of a tris-based extender, having the
      osmolality of 330 mOsm/kg and pH of 6.9, favors the short-term preservation of
      the Bactrian camel spermatozoa under chilled condition.

PMID- 16647051
TI  - Bacterial incorporation of leucine into protein down to -20 degrees C with
      evidence for potential activity in sub-eutectic saline ice formations.
AB  - Direct evidence for metabolism in a variety of frozen environments has pushed
      temperature limits for bacterial activity to increasingly lower temperatures, so
      far to -20 degrees C. To date, the metabolic activities of marine psychrophilic
      bacteria, important components of sea-ice communities, have not been studied in
      laboratory culture, not in ice and not below -12 degrees C. We measured [3H]
      leucine incorporation into macromolecules (further fractionated biochemically) by
      the marine psychrophilic bacterium Colwellia psychrerythraea strain 34H over a
      range of anticipated activity-permissive temperatures, from +13 to -20 degrees C,
      including expected negative controls at -80 and -196 degrees C. For incubation
      temperatures below -1 degrees C, the cell suspensions [all in artificial seawater
      (ASW)] were first quick-frozen in liquid nitrogen. We also examined the effect of
      added extracellular polymeric substances (EPS) on [3H]-leucine incorporation.
      Results showed that live cells of strain 34H incorporated substantial amounts of
      [3H]-leucine into TCA-precipitable material (primarily protein) down to -20
      degrees C. At temperatures from -1 to -20 degrees C, rates were enhanced by EPS.
      No activity was detected in the killed controls for strain 34H (or in Escherichia
      coli controls), which included TCA-killed, heat-killed, and sodium azide- and
      chloramphenicol-treated samples. Surprisingly, evidence for low but significant
      rates of intracellular incorporation of [3H]-leucine into protein was observed
      for both ASW-only and EPS-amended (and live only) samples incubated at -80 and 
      196 degrees C. Mechanisms that could explain the latter results require further
      study, but the process of vitrification promoted by rapid freezing and the
      presence of salts and organic polymers may be relevant. Overall, distinguishing
      between intracellular and extracellular aspects of bacterial activity appears
      important to understanding behavior at sub-freezing temperatures.

PMID- 16647052
TI  - Superoxide auto-augments superoxide formation and upregulates gp91(phox)
      expression in porcine pulmonary artery endothelial cells: inhibition by iloprost.
AB  - Central to the aetiology of Acute Respiratory Distress Syndrome (ARDS) is
      superoxide, the principal source of which is nicotinamide adenine dinucleotide
      phosphate oxidase (NADPH oxidase). To test whether superoxide may influence NADPH
      oxidase expression directly, the effect of incubation of superoxide with porcine
      pulmonary arterial endothelial cells on the expression of gp91(phox) (a catalytic
      subunit of NADPH oxidase) and superoxide formation was investigated. Since
      iloprost has been purported to be potentially effective in treating ARDS, the
      effect of iloprost on superoxide-mediated effects was also studied. Pulmonary
      artery endothelial cells were incubated with xanthine/xanthine oxidase which
      generates superoxide, or tumour necrosis factor alpha (TNFalpha) or thromboxane
      A(2) analogue, U46619 (+/- superoxide dismutase [SOD] or catalase or iloprost)
      for 16 h. Cells were then washed and superoxide formation assessed
      spectrophometrically and gp91(phox) expression using Western blotting. The role
      of NADPH oxidase was also studied in the above settings using apocynin, an NADPH
      oxidase inhibitor. Superoxide, TNFalpha and U46619 elicited an increase in the
      formation of superoxide and induced gp91(phox) expression in pulmonary artery
      endothelial cells following a 16 h incubation an effect blocked by the continual
      presence of SOD and apocynin but not catalase. Apocynin completely inhibited
      superoxide formation induced with xanthine/xanthine oxidase after the 16 h
      incubation. Rotenone and allopurinol were without effect. Iloprost inhibited the
      formation of superoxide and gp91(phox) expression. These data demonstrate that
      superoxide upregulates gp91(phox) expression in pulmonary artery endothelial
      cells and thus augments superoxide formation, an effect blocked by iloprost. This
      constitutes a novel mechanism by which vascular superoxide creates a self
      perpetuating cascade that may be of importance to the etiology of ARDS and other
      vasculopathies.

PMID- 16647053
TI  - Molecular cloning and pharmacological characterization of serotonin 5-HT(3A)
      receptor subtype in dog.
AB  - In order to establish if the canine 5-hydroxytryptamine type 3A (5-HT(3A))
      receptors share the pharmacological profile with human 5-HT(3A) receptors, we
      cloned and performed a molecular pharmacological characterization of the canine 5
      HT(3A) receptor. The 5-HT(3A) cDNA was cloned from canine brain by polymerase
      chain reaction amplification. It encodes a 483 amino acid peptide that exhibits
      from 80% (mice) to 90% (ferrets) identity to other sequenced mammalian 5-HT(3A)
      receptors. The receptor agonists 5-hydroxytryptamine (5-HT) and meta
      chlorophenylbiguanide (mCPBG) showed little differences between the two species,
      whereas 2-methyl-5-hydroxytryptamine (2-Me-5-HT) was ten times weaker at canine
      receptors than at human receptors. The potencies at the canine 5-HT(3) receptors
      were 9.9 microM (5-HT), 79 microM (2-Me-5-HT) and 0.8 microM (mCPBG). The
      selective, competitive receptor antagonist ondansetron was ten times more potent
      at human receptors compared to canine receptors (K(b)=0.9 nM), while (+)
      tubocurarine was 1000-fold more potent at canine receptors (K(b)=3.0 nM) than at
      human receptors. Examination of the presumed ligand binding extracellular domain
      revealed one residue, where the canine receptor differs from all previously
      characterized 5-HT(3A) receptors, i.e. other species contain a conserved
      Trp(195), whereas the canine orthologue contains a Leu(195). To address the
      differences in potencies at the human and canine 5-HT(3A) receptors seen in this
      study, we introduced a L195W point mutation in the canine orthologue. Data showed
      that the 195 residue can affect receptor agonist potency and efficacy as well as
      antagonist potency, but did produce a pharmacological profile identical to the
      human orthologue. We therefore conclude that position 195 is strongly involved in
      the receptor-ligand interaction, but additional residues must contribute to the
      overall pharmacological profile.

PMID- 16647054
TI  - Suppression by WIN55212-2, a cannabinoid receptor agonist, of inflammatory
      reactions in mouse ear: Interference with the actions of an endogenous ligand, 2
      arachidonoylglycerol.
AB  - The effect of WIN55212-2, a cannabinoid receptor agonist, on acute inflammation
      of mouse ear was investigated. We found that topical application of WIN55212-2
      suppressed ear swelling induced by 12-O-tetradecanoylphorbol 13-acetate or 2
      arachidonoylglycerol. Similar inhibition was observed with CP55940, another
      cannabinoid receptor agonist, and HU-308, a cannabinoid CB(2) receptor-selective
      agonist. WIN55212-2 also suppressed the infiltration of leukocytes induced by 12
      O-tetradecanoylphorbol 13-acetate. On the other hand, WIN55212-3, an inactive
      enantiomer of WIN55212-2, exerted only small effects on inflammation. Notably,
      SR144528, a cannabinoid CB(2) receptor antagonist, also suppressed inflammatory
      reactions in mouse ear. Thus, both the cannabinoid CB(2) receptor agonist and
      antagonist are capable of reducing inflammatory reactions. We then investigated
      the mechanism underlying WIN55212-2-induced suppression of inflammation using
      cultured cells. We found that the addition of WIN55212-2 together with 2
      arachidonoylglycerol blocked 2-arachidonoylglycerol-induced migration of human
      promyelocytic leukemia HL-60 cells that had been differentiated into macrophage
      like cells. The restoration of 2-arachidonoylglycerol-desensitized cells and
      WIN55212-2-desensitized cells from an anergic condition was examined next. We
      found that 2-arachidonoylglycerol-treated cells rapidly recovered the capacity to
      respond to 2-arachidonoylglycerol. On the other hand, the anergic condition
      toward 2-arachidonoylglycerol continued for a longer period after pretreatment
      with WIN55212-2. These results suggest that the anti-inflammatory activity of
      WIN55212-2 is attributable, at least in part, to interference with the actions of
      the endogenous ligand, 2-arachidonoylglycerol.

PMID- 16647055
TI  - Entamoeba histolytica: inflammatory process during amoebic liver abscess
      formation involves cyclooxygenase-2 expression in macrophages and trophozoites.
AB  - It has been demonstrated that expression of cyclooxygenase-2 (COX-2) isoform is
      induced by Entamoeba histolytica in macrophages and polymorphonuclear cells
      during amoebic liver abscess (ALA) formation in hamsters. Trophozoites present in
      the lesion were also positive for COX-2 signal. However, no cross reactivity of
      the anti-COX-2 antibody with protein extract of cultivated trophozoites was
      found. To clarify if trophozoites are involved in PGE(2) production during ALA
      development, COX-2 expression was detected by in situ hybridization and RT-PCR in
      liver tissue from intrahepatically infected hamsters. COX-2 mRNA was in
      polymorphonuclear cells since 4h postinfection, and subsequently, local
      macrophages expressed COX-2 mRNA in a similar way. Additionally, a positive
      signal for COX-2 mRNA expression was detected in E. histolytica trophozoites,
      suggesting that, in vivo, parasite COX expression may be an important mechanism
      to promote inflammation.

PMID- 16647056
TI  - Setaria digitata secreted filarial lipids modulate IL-12 signaling through JAK
      STAT pathway leading to the development of Th1 response.
AB  - Filariasis is a debilitating parasitic disease in many tropical countries.
      Despite the highly evolved immune system, the filarial parasites successfully
      evade host immunity to persist for a sustained period of time. Earlier studies
      have shown that the filarial parasites achieve this long-term survival through
      release of immunosuppressive materials in the host. In this study, we show that
      the secreted filarial lipids (SFL) isolated from Setaria digitata suppress Th1
      immune response. While immunization with myelin antigen induces Th1 response in
      mice, in vitro treatment with SFL resulted in a dose-dependent decrease in myelin
      antigen-induced proliferation and secretion of IL-12 and IFNgamma. The SFL also
      inhibited IL-12-induced T cell proliferation and Th1 differentiation in vitro.
      The inhibition of T cell responses by SFL associates with the blockade of IL-12
      induced activation of JAK-STAT signaling pathway in T cells. These findings
      suggest that the SFL modulates Th1 immune response by blocking IL-12 signaling in
      T cells and thus play a role in host immune evasion of filarial parasites.

PMID- 16647057
TI  - Escherichia coli engineered to produce eicosapentaenoic acid becomes resistant
      against oxidative damages.
AB  - The colony-forming ability of Escherichia coli genetically engineered to produce
      eicosapentaenoic acid (EPA) grown in 3mM hydrogen peroxide (H(2)O(2)) was similar
      to that of untreated cells. It was rapidly lost in the absence of EPA. H(2)O(2)
      induced protein carbonylation was enhanced in cells lacking EPA. The fatty acid
      composition of the transformants was unaffected by H(2)O(2) treatment, but the
      amount of fatty acids decreased in cultures of cells lacking EPA and increased in
      cultures of cells producing EPA, suggesting that cellular EPA is stable in the
      presence of H(2)O(2) in vivo and may protect cells directly against oxidative
      damage. We discuss the possible role of EPA in partially blocking the penetration
      of H(2)O(2) into cells through membranes containing EPA.

PMID- 16647058
TI  - Mouse model of human infertility: transient and local inhibition of endometrial
      STAT-3 activation results in implantation failure.
AB  - Embryo implantation involves a series of biochemical reactions and its failure is
      an important therapeutic target of infertility treatment. We established an
      infertile mouse model using transient and local suppression of signal transducer
      and activator of transcription-3 (STAT-3) activity by STAT-3 decoy transfer into
      the uterine cavity during implantation, resulting in <30% implantation. This
      infertility is caused by suppression of decidualization, which is indispensable
      for implantation, and independent of progesterone. These conditions may mimic
      clinically unexplained infertility. Our results suggest that STAT-3 could be a
      useful target for diagnosis and therapy of human implantation failure.

PMID- 16647059
TI  - Substrate-induced double sided H-bond network as a means of domain closure in 3
      phosphoglycerate kinase.
AB  - Closure of the two domains of 3-phosphoglycerate kinase, upon substrate binding,
      is essential for the enzyme function. The available crystal structures cannot
      provide sufficient information about the mechanism of substrate assisted domain
      closure and about the requirement of only one or both substrates, since lattice
      forces may hinder the large scale domain movements. In this study the known X-ray
      data, obtained for the open and closed conformations, were probed by solution
      small-angle X-ray scattering experiments. The results prove that binding of both
      substrates is essential for domain closure. Molecular graphical analysis, indeed,
      reveals formation of a double-sided H-bond network, which affects substantially
      the shape of the main molecular hinge at beta-strand L, under the concerted
      action of both substrates.

PMID- 16647060
TI  - Crystal structure of AmyA lacks acidic surface and provide insights into protein
      stability at poly-extreme condition.
AB  - Here we report the first crystal structure of a protein, AmyA, a secretory alpha
      amylase isolated from Halothermothrix orenii, which is both halophilic and
      thermophilic. The crystal structure was determined at 1.6 A resolution. AmyA
      lacks the conserved acidic surface, which is considered essential for protein
      stability at high salinity. Sedimentation velocity and CD experiments on AmyA
      reveal the formation of unique reversible poly-dispersed oligomers that show
      unusually high thermal stability. These studies provide valuable insight into the
      structural elements that contribute to the stability of AmyA at both physical and
      chemical extremes and their functional implications.

PMID- 16647061
TI  - Enzymatic activity of the SARS coronavirus main proteinase dimer.
AB  - The enzymatic activity of the SARS coronavirus main proteinase dimer was
      characterized by a sensitive, quantitative assay. The new, fluorogenic substrate,
      (Ala-Arg-Leu-Gln-NH)(2)-Rhodamine, contained a severe acute respiratory syndrome
      coronavirus (SARS CoV) main proteinase consensus cleavage sequence and Rhodamine
      110, one of the most detectable compounds known, as the reporter group. The gene
      for the enzyme was cloned in the absence of purification tags, expressed in
      Escherichia coli and the enzyme purified. Enzyme activity from the SARS CoV main
      proteinase dimer could readily be detected at low pM concentrations. The enzyme
      exhibited a high K(m), and is unusually sensitive to ionic strength and reducing
      agents.

PMID- 16647062
TI  - Chitooligosaccharides inhibit activation and expression of matrix
      metalloproteinase-2 in human dermal fibroblasts.
AB  - Recently, much attention has been given to chitosan and its hydrolyzed products
      due to their diverse biological activities. For the first time here we report the
      inhibitory effect of chitooligosaccharides (COS) on activation and expression of
      matrix metalloproteinase-2 (MMP-2) in primary human dermal fibroblasts (HDFs).
      COS with 3-5 kDa exhibited the highest inhibitory effect on MMP-2 activity in
      HDFs assessed by gelatin zymography. Interestingly, protein expression of MMP-2
      was also inhibited by COS with same molecular weight. This inhibition was caused
      by the decrease of the gene expression and transcriptional activity of MMP-2.
      Furthermore, it was found that COS repressed the gene expression of c-fos, a part
      of AP-1 transcription factor. These results suggest that COS may play an
      important role in the prevention and treatment of MMP-2 mediated several health
      problems such as metastasis and wrinkle formation.

PMID- 16647063
TI  - A critical role for the histidine residues in the catalytic function of acyl
      CoA:cholesterol acyltransferase catalysis: evidence for catalytic difference
      between ACAT1 and ACAT2.
AB  - To investigate a role for histidine residues in the expression of normal acyl
      CoA:cholesterol acyltransferase (ACAT) activity, the histidine residues located
      at five different positions in two isoenzymes were substituted by alanine, based
      on the sequence homology between ACAT1 and ACAT2. Among the 10 mutants generated
      by baculovirus expression technology, H386A-ACAT1, H460A-ACAT1, H360A-ACAT2, and
      H399A-ACAT2 lost their enzymatic activity completely. A reduction in catalytic
      activity is unlikely to result from structural changes in the substrate-binding
      pocket, because their substrate-binding affinities were normal. However, the
      enzymatic activity of H386A-ACAT1 was restored to <37% of the level of the wild
      type activity when cholesterol was replaced by 25-hydroxycholesterol as
      substrate. H527A-ACAT1 and H501A-ACAT2, termed carboxyl end mutants, exhibit
      activities of approximately 96% and approximately 75% of that of the wild-type.
      Interestingly, H425A-ACAT1 showed 59% of the wild-type activity, in contrast to
      its equivalent mutant, H399A-ACAT2. These results demonstrate that the histidine
      residues located at the active site are very crucial both for the catalytic
      activity of the enzyme and for distinguishing ACAT1 from ACAT2 with respect to
      enzyme catalysis and substrate specificity.

PMID- 16647064
TI  - The role of molecular modelling in biomedical research.
AB  - The synergy between experimental and computational biology has greatly benefited
      both fields, providing invaluable information in many different areas of the life
      sciences. This minireview will focus on one specific aspect of computational
      biology, molecular modelling, and describe a few examples highlighting the
      effectiveness of protein structural analysis and modelling in providing relevant
      information about systems of biomedical interest.

PMID- 16647065
TI  - The Swi/Snf chromatin remodeling complex is essential for hyphal development in
      Candida albicans.
AB  - The ability of dimorphic transition between yeast and hyphal forms in Candida
      albicans is one of the vital determinants for its pathogenicity and virulence. We
      isolated C. albicans SWI1 as a suppressor of the invasive growth defect in a
      Saccharomyces cerevisiae mutant. Expression of C. albicans SWI1 in S. cerevisiae
      partially complemented the growth defect of a swi1 mutant in the utilization of
      glycerol. Swi1 is in a complex with Snf2 in C. albicans, and both proteins are
      localized in the nucleus independent of the growth form. Deleting SWI1 or SNF2 in
      C. albicans prevented true hyphal formation and resulted in constitutive
      pseudohypha-like growth in all media examined. Furthermore, swi1/swi1 mutant was
      defective in hypha-specific gene expression and avirulent in a mouse model of
      systemic infection. These data strongly suggest the conserved Swi/Snf complex in
      C. albicans is required for hyphal development and pathogenicity.

PMID- 16647066
TI  - Expanding to fill the gap: a possible role for inert biopolymers in regulating
      the extent of the 'macromolecular crowding' effect.
AB  - We discuss the potential for inert biopolymers existing in cells to play a role
      in regulating the macromolecular crowding effect via their ability to undergo
      shape changing structural transitions. We have explored this possibility by the
      use of theory and experiment. The theoretical component utilized Monte-Carlo
      based simulations to examine the folding of a hypothetical protein in a
      concentrated environment of hard spheres which are themselves capable of
      reversible expansion and contraction. The experimental component of the study
      involved examination of the effect of different sized crowding agents on the
      thermally induced denaturation of cytochrome c [in phosphate buffered saline
      solution containing 1.0M guanidinium hydrochloride at pH 7.0]. On the basis of
      our findings we suggest that in a crowded solution environment the presence of a
      non-reactive polymer capable of reversible expansion/contraction via folding and
      unfolding may alter the excluded volume component of the solution. This ability
      would confer on the non-reactive polymer a novel role in influencing other
      processes in solution affected by macromolecular crowding.

PMID- 16647067
TI  - Generation of cell lines with tetracycline-regulated autophagy and a role for
      autophagy in controlling cell size.
AB  - Autophagy is an intracellular bulk degradation system. We established mouse
      fibroblast lines coupling the Tet-off system with an Atg5(-/-) mouse embryonic
      fibroblast line to artificially regulate autophagic ability. In the presence of
      doxycycline (Dox), Atg5 expression was completely suppressed and these cells were
      autophagy-defective. After removal of Dox, autophagic ability was restored within
      6h. Very low levels of Atg5 could induce an autophagy competent state. We applied
      this novel system to examine the contribution of autophagy to controlling cell
      size. Cell size reduction in response to starvation was significantly inhibited
      in cells unable to undergo autophagy. The generated cell lines will be useful
      reagents for future mechanistic studies into the regulation and physiologic
      significance of autophagy.

PMID- 16647068
TI  - Increased Src kinase level results in increased protein tyrosine phosphorylation
      in scrapie-infected neuronal cell lines.
AB  - We have studied how prion infection may affect the Src kinase activity in three
      different neuronal cell lines, ScGT1 and ScN2a, where ScGT1 were generated in our
      laboratory. By immunoblotting, using clone 28 - a monoclonal antibody recognizing
      active Src, we have found a 32+/-6.3% and 75+/-7.7% elevation in Src activity in
      ScGT1 and ScN2a cells, respectively, compared to uninfected cells. Immunocomplex
      in vitro kinase assay confirmed the increased Src activity. The increased Src
      kinase activity in scrapie-infected cells was further shown to correlate to an
      increased level of Src protein. In addition, an important increase in the protein
      tyrosine phosphorylation signal was observed in ScGT1 and ScN2a cells, which was
      further shown to be Src-dependent, as treatment with PP2 - a Src family kinase
      specific inhibitor, reversed the protein tyrosine phosphorylation profile.
      Abnormal Src-kinase activation and subsequent protein tyrosine phosphorylation
      may be key elements in the neuropathology of the prion diseases.

PMID- 16647069
TI  - Constitutive activation of the jasmonate signaling pathway enhances the
      production of secondary metabolites in tomato.
AB  - The phytohormone jasmonic acid (JA) regulates the synthesis of secondary
      metabolites in a wide range of plant species. Here, we show that exogenous methyl
      JA (MeJA) elicits massive accumulation of caffeoylputrescine (CP) in tomato
      leaves. A mutant (jai1) that is defective in jasmonate perception failed to
      accumulate CP in flowers and MeJA-treated leaves. Conversely, a transgenic tomato
      line (called 35S::PS) that exhibits constitutive JA signaling accumulated high
      levels of leaf CP in the absence of jasmonate treatment. RNA blot analysis showed
      that genes encoding enzymes in the phenylpropanoid and polyamine pathways for CP
      biosynthesis are upregulated in MeJA-treated wild-type plants and in untreated
      35S::PS plants. These results indicate that CP accumulation in tomato is tightly
      controlled by the jasmonate signaling pathway, and provide proof-of-concept that
      the production of some plant secondary metabolites can be enhanced by transgenic
      manipulation of endogenous JA levels.

PMID- 16647070
TI  - Role of thioredoxin-1 in apoptosis induction by alpha-tocopheryl succinate and
      TNF-related apoptosis-inducing ligand in mesothelioma cells.
AB  - Malignant mesothelioma (MM) is a fatal type of cancer. We studied the role of the
      redox-active protein thioredoxin-1 (Trx-1) in apoptosis induced in MM cells and
      their non-malignant counterparts (Met-5A) by alpha-tocopheryl succinate (alpha
      TOS) and TNF-related apoptosis-inducing ligand (TRAIL). MM cells were susceptible
      to alpha-TOS and less to TRAIL, while Met-5A cells were susceptible to TRAIL and
      resistant to alpha-TOS. MM cells expressed very low level of the Trx-1 protein,
      which was high in Met-5A cells, while the level of Trx-1 mRNA was similar in all
      cell lines. Downregulation of Trx-1 further sensitised Met-5A cells to TRAIL but
      not to alpha-TOS. Our data suggest that the role of Trx-1 in apoptosis modulation
      is unrelated to its anti-oxidant properties.

PMID- 16647071
TI  - Differential expression of HR38 in the mushroom bodies of the honeybee brain
      depends on the caste and division of labor.
AB  - We used a cDNA microarray to identify genes expressed in a caste (worker)- and
      division of labor (nurse bees or foragers)-dependent manner in the honeybee
      brain. Among the identified genes, one encoded a putative orphan receptor (HR38)
      homologue that mediates ecdysteroid-signaling. Real-time reverse transcription
      polymerase chain reaction indicated that expression of this gene is higher in
      forager brains, as compared to nurse bees and queens. In the forager brain,
      expression was concentrated in a subset of the mushroom body neurons, suggesting
      that ecdysteroid-signaling in the mushroom bodies might be involved in the
      division of labor of the workers.

PMID- 16647072
TI  - Isolation of Escherichia coli inner membranes by metal affinity two-phase
      partitioning.
AB  - As reduction of sample complexity is a central issue in membrane proteomic
      research, the need for new pre-fractionation methods is significant. Here we
      present a method for fast and efficient enrichment of Escherichia coli inner
      membranes expressing a His-tagged integral membrane L-fucose-proton symporter
      (FucP). An enriched inner membrane fraction was obtained from a crude membrane
      mixture using affinity two-phase partitioning in combination with nickel
      nitrilotriacetic acid (Ni-NTA) immobilized on agarose beads. Due to interaction
      between the beads and FucP, inner membranes were selectively partitioned to the
      bottom phase of a polymer/polymer aqueous two-phase system consisting of
      poly(ethylene glycol) (PEG) and dextran. The partitioning of membranes was
      monitored by assaying the activity of an inner membrane marker protein and
      measuring the total protein content in both phases. The enrichment of inner
      membrane proteins in the dextran phase was also investigated by proteomic
      methodology, including sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE), trypsin digestion and liquid chromatography in combination with
      tandem mass spectrometry (LC-MS/MS). Using a high level of significance (99.95%)
      in the subsequent database search, 36 proteins assigned to the inner membrane
      were identified in the bottom phase, compared to 29 when using the standard
      sucrose gradient centrifugation method for inner membrane isolation. Furthermore,
      metal affinity two-phase partitioning was up to 10 times faster than sucrose
      gradient centrifugation. The separation conditions in these model experiments
      provide a basis for the selective isolation of E. coli membranes expressing His
      tagged proteins and can therefore facilitate research on such membrane proteomes.

PMID- 16647073
TI  - Potential of membrane-assisted solvent extraction for the determination of
      phosphoric acid triesters in wastewater samples by liquid chromatography-tandem
      mass spectrometry.
AB  - A membrane-assisted solvent extraction (MASE) method is presented for the
      extraction of several non-ionic organophosphorus chemicals from wastewaters
      samples followed by LC-MS/MS determination. The method was developed for a
      variety of chlorinated phosphates (trichloroethyl, tichloropropyl) and non
      chlorinated phosphates (triphenyl, tributyl) used as flame retardants and for
      plasticizers such as triethylhexyl and tris-butoxyethyl phosphate. Parameters
      such as extracting solvent, sample volume and ionic strength, extraction
      temperature and time were optimized. The final method provides good
      quantification limits (1-25 ng L(-1)) and linearity (R2>0.9978). Method precision
      was also good at high concentrations (5% mean RSD at the 500 ng L(-1) level) but
      decreased at lower concentrations (20% mean RSD at the 20 ng L(-1) level). MASE
      yields lower matrix effects than SPE in a successive LC-MS/MS analysis of these
      compounds, avoiding the need for standard addition for quantification. When
      applied to wastewater samples comparable results were obtained using either MASE
      with internal standard calibration or SPE with standard addition.

PMID- 16647074
TI  - Liquid chromatography, electrochromatography and capillary electrophoresis
      applications of DNA and RNA aptamers.
AB  - The development of the systematic evolution of ligands by exponential enrichment
      (SELEX) process has allowed the isolation of oligonucleotide sequences (referred
      as aptamers) with the capacity to recognize various classes of target molecules
      with high affinity and specificity. At the present time, various analytical
      aptamer-based formats have been developed as suitable tools for the detection and
      quantification of numerous targets, possessing many potential advantages over the
      most popular antibody technology. In this review, the aptamer applicability to
      the separation, purification and quantification of various analytes by liquid
      chromatography, capillary electrophoresis and electrochromatography is addressed.

PMID- 16647075
TI  - Synthesis, characterization, and catalytic activity of phosphomolybdic acid
      supported on hydrous zirconia.
AB  - A series of ecofriendly solid acid catalyst was synthesized by phosphomolybdic
      acid impregnated on hydrous zirconia (ZPMA) by an incipient wetness impregnation
      technique. The support and the resulting catalysts were characterized by X-ray
      diffraction, FTIR, EPMA, BET surface area, acid sites, etc. These studies
      indicate that the phosphomolybdic acid keeps its Keggin-type structure unaltered
      up to 500 degrees C. Catalytic activities of the material were evaluated for the
      esterification of acetic acid reaction. The 12 wt% of phosphomolybdic acid
      supported on hydrous zirconia shows highest surface area, acid sites and gives
      about 86% conversion with 100% selectivity of n-butyl acetate.

PMID- 16647076
TI  - A simple route utilizing surfactant-assisted templating sol-gel process for
      synthesis of mesoporous Dy2O3 nanocrystal.
AB  - A simple route of combined sol-gel process with surfactant-assisted templating
      technique was successfully employed for the first time to synthesize
      nanocrystalline mesoporous Dy(2)O(3) with narrow monomodal pore size distribution
      under mild conditions. The nanocrystalline Dy(2)O(3) with monomodal mesoporous
      characteristic was ultimately achieved by controlling the hydrolysis and
      condensation steps of dysprosium n-butoxide modified with acetylacetone in the
      presence of laurylamine hydrochloride surfactant aqueous solution. The
      synthesized material was methodically characterized by thermogravimetry and
      differential thermal analysis (TG-DTA), X-ray diffraction (XRD), scanning
      electron microscopy (SEM), high resolution transmission electron microscopy
      (HRTEM), selected-area electron diffraction (SAED), N(2) adsorption-desorption,
      Brunauer-Emmett-Teller (BET) surface area analysis, and Barrett-Joyner-Halenda
      (BJH) pore size distribution analysis. The particle size of the synthesized
      Dy(2)O(3) in nanosized range obtained from the SEM and HRTEM micrographs was in
      good accordance with the crystallite size estimated from the XRD result. The N(2)
      adsorption-desorption result exhibited hysteresis pattern with single loop,
      indicating the existence of monomodal mesopore. The extremely narrow pore size
      distribution with mean pore diameter in the mesopore region of the synthesized
      Dy(2)O(3) was also confirmed by the BJH result.

PMID- 16647077
TI  - Adsorption of hexyl-alpha,omega-bis(dodecyldimethylammonium bromide) gemini
      surfactant on silica and its effect on wettability.
AB  - The adsorption of hexyl-alpha,omega-bis(dodecyldimethylammonium bromide)
      (C(12)C(6)C(12)Br(2)) gemini surfactant on silica and its effect on wettability
      have been studied. The structure of the adsorbed aggregates experiences an
      evolving course with the increase of C(12)C(6)C(12)Br(2) concentration. It is
      from no aggregates to circular islands, then to semicontinuous islands, and at
      last to the two-bilayer structure. No matter what kind of aggregates are in
      existence, their thickness values are to be the same 3.3+/-0.3 nm. The fraction
      of silica surface covered by the surfactant aggregates also varies from nearly
      zero at 0.05 mM to approximately 0.92 at 5.0 mM. The variation of contact angle
      against C(12)C(6)C(12)Br(2) concentration shows two distinct regions. The upward
      shift indicates that the surfactant molecules are adsorbed with their hydrophobic
      tails facing air upon increasing concentration, while the downward shift reveals
      that the surfactant aggregates are in existence with the hydrophilic headgroups
      facing air. IR spectra suggest that two different courses are involved with the
      increase of the surfactant concentration. One possible course is that the
      surfactant tails pack more closely and orderly, and the other may be that the
      spacer changes from stretched profile to bended conformation upon increasing the
      surfactant concentration.

PMID- 16647078
TI  - NMR diffusometry and conductometry study of the host-guest association between
      beta-cyclodextrin and dodecane 1,12-bis(trimethylammonium bromide).
AB  - Surfactants form association complexes with cyclodextrins. In the present
      investigation we have used NMR-diffusometry and electrical conductivity to follow
      the interactions which take place between beta-cyclodextrin and a bolaform
      surfactant: dodecane 1,12-bis(trimethylammonium bromide). Both (1)H NMR self
      diffusion and conductometry data indicate the formation of a 1:1 inclusion
      complex. Assuming this stoichiometry, it was possible to calculate the
      association constant; from the analysis of the self-diffusion coefficients of
      free beta-cyclodextrin and the bolaform surfactant an association constant
      K=3x10(3)M(-1) was obtained while the analysis of conductivity data gave a
      comparable value of K=2.5x10(3)M(-1).

PMID- 16647079
TI  - Flow-injection chemiluminescent immunoassay for alpha-fetoprotein based on
      epoxysilane modified glass microbeads.
AB  - A flow-injection chemiluminescent immunoassay system based on a novel transparent
      immunoaffinity reactor is proposed for the quantitation of alpha-fetoprotein. The
      reactor prepared with alpha-fetoprotein immobilized epoxysilane modified glass
      microbeads was used as an immunosensor for chemiluminescent detection. With a non
      competitive immunoassay format, the proposed immunosensor system is a low cost,
      flexible and rapid assay for alpha-fetoprotein. After an off-line incubation of
      the analyte alpha-fetoprotein with horseradish peroxidase-labeled alpha
      fetoprotein antibody as enzyme tracer, the mixture was injected into the reactor,
      which led to trapping of the free enzyme tracer by the reactor. The trapped
      enzyme tracer was detected by the p-iodophenol-luminol-H2O2 chemiluminescence
      system. Under optimal conditions, the decrease in chemiluminescence intensity was
      proportional to the alpha-fetoprotein concentration in the range of 5.0-100 ng/ml
      with a detection limit of 2.7 ng/ml at a signal/noise ratio of 3. The
      immunosensor system showed an acceptable reproducibility and stability. Clinical
      serum samples were assayed with this method and the results were in acceptable
      agreement with those obtained from immunoradiometric assay.

PMID- 16647080
TI  - Detection of macaque perforin expression and release by flow cytometry,
      immunohistochemistry, ELISA, and ELISpot.
AB  - Simian immunodeficiency virus (SIV)-infection in macaques provides an important
      animal model for human immunodeficiency virus-1 (HIV-1) infection. The
      involvement of perforin (PFN), released by cytotoxic cells to mediate killing of
      virus-infected cells, has been difficult to assess in this experimental model due
      to a lack of reagents. We therefore evaluated monoclonal antibodies (mAbs) Pf-80,
      Pf-164 and Pf-344, previously raised against human PFN, for cross-reactivity with
      macaque PFN. Mabs Pf-164 and Pf-344 reacted with intracellular PFN in peripheral
      blood mononuclear cells (PBMC) from cynomolgus and rhesus macaques by flow
      cytometry and stained PFN in rhesus lymphoid tissue by immunohistochemistry
      (IHC). Moreover, PFN capture enzyme-linked immunosorbent (ELISA) and enzyme
      linked immunospot (ELISpot) assays utilizing mAbs Pf-164/Pf-80 for capture and
      mAb Pf-344 for detection were used to quantify PFN release by mitogen-stimulated
      cynomolgus and rhesus PBMC. The PFN ELISpot was further used to quantify antigen
      specific CD8+ T cells by ex vivo stimulation of PBMC from cynomolgus macaques
      immunized against SIV/HIV-1. These macaque PFN-reactive mAbs and immunoassays
      will be valuable new tools for investigation of cytotoxic T lymphocyte (CTL)
      responses in non-human primate models of infectious diseases as well as for
      vaccine development.

PMID- 16647081
TI  - Switchover to the mated state by spermathecal activation in female Anopheles
      gambiae mosquitoes.
AB  - Both Aedes aegypti and Anopheles gambiae mosquitoes undergo physiological and
      behavioral changes after the females mate, but unlike Ae. aegypti, the mated
      state in An. gambiae is not attained through the action of male accessory gland
      substances. Experiments in which the spermathecae of mated females were
      manipulated suggest that a spermatheca filled with sperm is responsible for
      triggering oviposition behavior. An estimated 48% of the previously mated An.
      gambiae females mated again when the interval between encounters with males was
      less than 24h. Unlike male Ae. aegypti that can inseminate up to seven females
      after their testes are removed, An. gambiae do not store sperm in the vas
      deferens and without testes would be unable to inseminate any females.

PMID- 16647082
TI  - Crystal structure of a novel beta-lactam-insensitive peptidoglycan
      transpeptidase.
AB  - During the final stages of cell-wall synthesis in bacteria, penicillin-binding
      proteins (PBPs) catalyse the cross-linking of peptide chains from adjacent glycan
      strands of nascent peptidoglycan. We have recently shown that this step can be
      bypassed by an L,D-transpeptidase, which confers high-level beta-lactam
      resistance in Enterococcus faecium. The resistance bypass leads to replacement of
      D-Ala4-->D-Asx-L-Lys3 cross-links generated by the PBPs by L-Lys3-->D-Asx-L-Lys3
      cross-links generated by the L,D-transpeptidase. As the first structure of a
      member of this new transpeptidase family, we have determined the crystal
      structure of a fragment of the L,D-transpeptidase from E.faecium (Ldt(fm217)) at
      2.4A resolution. Ldt(fm217) consists of two domains, the N-terminal domain, a new
      mixed alpha-beta fold, and the ErfK_YbiS_YhnG C-terminal domain, a representative
      of the mainly beta class of protein structures. Residue Cys442 of the C-terminal
      domain has been proposed to be the catalytic residue implicated in the cleavage
      of the L-Lys-D-Ala peptide bond. Surface analysis of Ldt(fm217) reveals that
      residue Cys442 is localized in a buried pocket and is accessible by two paths on
      different sides of the protein. We propose that the two paths to the catalytic
      residue Cys442 are the binding sites for the acceptor and donor substrates of the
      L,D-transpeptidase.

PMID- 16647083
TI  - Crystal structure of the nucleotide-binding subunit DhaL of the Escherichia coli
      dihydroxyacetone kinase.
AB  - Dihydroxyacetone (Dha) kinases are a family of sequence-related enzymes that
      utilize either ATP or phosphoenolpyruvate (PEP) as source of high energy
      phosphate. The PEP-dependent Dha kinase of Escherichia coli consists of three
      subunits. DhaK and DhaL are homologous to the Dha and nucleotide-binding domains
      of the ATP-dependent kinase of Citrobacter freundii. The DhaM subunit is a
      multiphosphorylprotein of the PEP:sugar phosphotransferase system (PTS). DhaL
      contains a tightly bound ADP as coenzyme that gets transiently phosphorylated in
      the double displacement of phosphate between DhaM and Dha. Here we report the
      2.6A crystal structure of the E.coli DhaL subunit. DhaL folds into an eight-helix
      barrel of regular up-down topology with a hydrophobic core made up of eight
      interlocked aromatic residues and a molecule of ADP bound at the narrower end of
      the barrel. The alpha and beta phosphates of ADP are complexed by two Mg2+ and by
      a hydrogen bond to the imidazole ring of an invariant histidine. The Mg ions in
      turn are coordinated by three gamma-carboxyl groups of invariant aspartate
      residues. Water molecules complete the octahedral coordination sphere. The
      nucleotide is capped by an alpha-helical segment connecting helices 7 and 8 of
      the barrel. DhaL and the nucleotide-binding domain of the C.freundii kinase
      assume the same fold but display strongly different surface potentials. The
      latter observation and biochemical data indicate that the domains of the
      C.freundii Dha kinase constitute one cooperative unit and are not randomly
      interacting and independent like the subunits of the E.coli enzyme.

PMID- 16647084
TI  - Structure of the Epstein-Barr virus oncogene BARF1.
AB  - The Epstein-Barr virus is a human gamma-herpesvirus that persistently infects
      more than 90% of the human population. It is associated with numerous epithelial
      cancers, principally undifferentiated nasopharyngeal carcinoma and gastric
      carcinoma. The BARF1 gene is expressed in a high proportion of these cancers. An
      oncogenic, mitogenic and immortalizing activity of the BARF1 protein has been
      shown. We solved the structure of the secreted BARF1 glycoprotein expressed in a
      human cell line by X-ray crystallography at a resolution of 2.3A. The BARF1
      protein consists of two immunoglobulin (Ig)-like domains. The N-terminal domain
      belongs to the subfamily of variable domains whereas the C-terminal one is
      related to a constant Ig-domain. BARF1 shows an unusual hexamerisation involving
      two principal contacts, one between the C-terminal domains and one between the N
      terminal domains. The C-terminal contact with an uncommonly large contact surface
      extends the beta-sandwich of the Ig-domain through the second molecule. The N
      terminal contact involves Ig-domains with an unusual relative orientation but
      with a more classical contact surface with a size in the range of dimer
      interactions of Ig-domains. The structure of BARF1 is most closely related to
      CD80 or B7-1, a co-stimulatory molecule present on antigen presenting cells, from
      which BARF1 must have been derived during evolution. Still, domain orientation
      and oligomerization differ between BARF1 and CD80. It had been shown that BARF1
      binds to hCSF-1, the human colony-stimulating factor 1, but this interaction has
      to be principally different from the one between CSF-1 and CSF-1 receptor.

PMID- 16647085
TI  - Alcohol-impaired driving and its consequences in the United States: the past 25
      years.
AB  - INTRODUCTION: Progress in dealing with the alcohol-impaired driving problem in
      the United States during the past 25 years is addressed. METHODS: Trends in
      various measures of the problem were tracked and a thorough review of the
      relevant literature conducted. RESULTS: In the 1980s and continuing into the
      early 1990s, major decreases occurred in alcohol-impaired driving and its
      consequences. The contribution of alcohol to fatal crashes dropped by 35-40%
      during this period. Two primary reasons for the decline appear to be the
      emergence of citizen activist groups that mobilized public support and attention
      to the problem, and the proliferation of effective laws. Since about 1995 the
      alcohol-impaired driving problem has stabilized at a reduced but still quite high
      level. CONCLUSIONS: Highway safety organizations and citizen activist groups have
      continued to highlight the problem, but its status as a social issue has
      diminished. We basically know what the primary target groups are, and we know
      measures that would work to reduce the problem if implemented more fully. We know
      that political leadership, state task forces, and media advocacy are important
      ingredients in addressing the problem. It is likely that a resurgence in citizen
      activism will be necessary to foster these elements and refocus the nation on the
      unfinished battle against alcohol-impaired driving. IMPACT ON INDUSTRY: Alcohol
      impaired driving is still a major problem that needs continuing attention.

PMID- 16647086
TI  - Reduced thalamic and cerebellar rest metabolism in relapsing-remitting multiple
      sclerosis, a positron emission tomography study: correlations to lesion load.
AB  - Magnetic resonance imaging (MRI) is the main tool for detecting central nervous
      system lesions in MS. However, classical anatomical MRI is unable to assess
      exactly disease related injury in normal-appearing brain tissue and to give
      information about the functional consequences of the disease, explaining weak
      correlation frequently observed between lesion load and clinical data. Recently,
      functional brain imaging techniques have provided new insights concerning
      pathophysiological processes of the disease. Among them Positron Emission
      Tomography (PET), a sensitive technique to evaluate functional consequences of
      tissue injury in other neurological diseases, has rarely been used in MS.
      Seventeen Relapsing-Remitting (RR-) MS patients with low disability at the early
      stage of the disease underwent measurements of cerebral metabolic rate of glucose
      (rCMRglu) in resting state by PET using [(18)F] fluorodeoxyglucose (FDG) and
      assessment of regional cortical and white matter lesion volume (LV), using an in
      house-developed semi-automatic method, was done at the same time on MRI. rCMRglu
      of MS patients was compared with rCMRglu of 18 normal control subjects using
      univariate SPM99 analysis through Matlab 5 and correlations between rCMRglu and
      LV were tested using multivariate linear regression using SPM99. Statistical
      threshold was set at p<0.05 corrected for multiple comparisons and correlations.
      Compared to controls, reduced rCMRglu was found in the right thalamus (p<0.001),
      in bilateral cerebellum (p<0.05 for right and p<0.01 for left) and the posterior
      part of left inferior parietal cortex (p<0.05). In addition, higher rCMRglu in
      patients compared to controls was observed in left inferior frontal cortex, left
      (anterior part) and right inferior parietal cortex (p<0.001). rCMRglu in right
      thalamus correlates negatively with different LV: total LV, total juxtacortical
      and/or overlapping cortico-subcortical LV, total and frontal deep white matter
      LV. rCMRglu of the right superior frontal cortex negatively correlated with total
      and parieto-occipital deep white matter LV. The results of this study, performed
      in a group of recent RR-MS patients with low disability, suggest that
      demyelinating lesions in MS mainly have a remote effect on cortical, basal
      ganglia and cerebellum metabolism and that regional cortical compensatory
      mechanisms may be observed concurrently.

PMID- 16647087
TI  - The lower subscapular nerve conduction studies and utilisation in brachial
      plexopathy evaluation.
AB  - OBJECTIVE: To define the optimal nerve conduction study (NCS) method of lower
      subscapular nerve and evaluate its clinical utility. METHODS: Thirty healthy
      adults (8 males) with a mean age of 45.2+/-16.5 (range, 21-75) years were
      recruited in this study. A total of sixty nerves were studied using the Dantec
      Counterpoint EMG machine (Dantec, Skovlunde, Denmark). 6 patients with clinical
      and electrodiagnostic evidence of brachial plexopathy were also evaluated.
      RESULTS: The mean+/-2 standard deviation values of the distal latencies, base-to
      peak amplitudes and inter-side amplitude ratio were 2.38+/-0.52 (range, 1.80
      2.90) ms, 13.10+/-5.10 (range, 8.70-21.10) mV and 0.93+/-0.12 (range, 0.67-1.00),
      respectively. There was a significant correlation between the subject age and the
      base-to-peak amplitudes. All 6 patients with brachial plexopathy had reduced base
      to-peak amplitudes as well as inter-side amplitude ratio of less than 0.67 (the
      normal limits for control). CONCLUSION: The lower subscapular NCS were
      satisfactorily recordable and well tolerated. It was useful in evaluation of
      patients with brachial plexopathy.

PMID- 16647088
TI  - Non-invasive positive pressure ventilation for laryngeal contraction disorder
      during sleep in multiple system atrophy.
AB  - We examined the usefulness of non-invasive positive pressure ventilation (NPPV)
      in the management of nocturnal laryngeal stridor associated with vocal cord
      dysfunction in five cases of multiple system atrophy (MSA). First, the patients
      were investigated during sleep induced by a minimal dose of propofol.
      Laryngoscopy showed paradoxical vocal cord movement resulting in inspiratory
      stridor. Electromyographic (EMG) study revealed synchronized bursts in the
      thyroarytenoid muscles and diaphragm in every inspiratory phase whenever the
      stridor emerged. NPPV was initiated after paradoxical movement was recognized
      with laryngoscopy. The NPPV mask was equipped with an additional channel for
      laryngoscopic monitoring. The optimal pressure for treatment was determined
      according to laryngoscopic and EMG findings. Next, NPPV was applied to natural
      sleep using the conditions determined in propofol-induced sleep. In all cases,
      NPPV eliminated nocturnal stridor and oxygen desaturation during natural sleep.
      Laryngoscopic observation during induced sleep is recommended as a useful
      procedure to titrate the optimal pressure for NPPV therapy. Since central
      hypoventilation progresses in the course of MSA, the choice of NPPV rather than
      continuous positive airway pressure should be encouraged to treat laryngeal
      contraction disorder associated with MSA.

PMID- 16647089
TI  - Cognitive impairment in newly diagnosed multiple sclerosis patients: a 4-year
      follow-up study.
AB  - Cognitive impairment occurs in early multiple sclerosis (MS), may decline over
      time, and has major impact on social functioning. The objectives of this study
      were to examine cognitive functioning in newly diagnosed MS, and to follow up
      over a period of 5 years. The results of the first three yearly re-examinations
      are reported. Eighty newly diagnosed (<1 year) MS patients participated
      (male/female: 19:61, mean age: 35 years, mean EDSS 2.7, course: 75 relapsing
      remitting, 3 primary progressive, 2 secondary progressive). Seventy-five healthy
      persons served as controls. The neuropsychological (NP) test battery comprised 30
      test measures and was grouped into seven cognitive domains. A residual score of 
      1.5 SD as cut-off point was used to diagnose cognitive impairment. At the first
      examination, 44-48% had cognitive impairment. None of the patients were
      clinically depressed, 51% had no signs of depression on Beck Depression Inventory
      (BDI), and none had severe signs. Sixty-four patients completed four
      examinations, and a significant linear improvement over time was seen in three
      cognitive domains, no change in two domains, and deterioration in one domain. At
      the time of the fourth examination, 4.3 years since diagnosis, 33-34% of the
      patients had cognitive impairment. Thirty percent of the patients were on
      disablement pension, 34% received social services in relation to work and 13% had
      home care. Methodological problems are discussed, especially the practice effect
      and the importance of identifying sensitive and stable test measures.

PMID- 16647090
TI  - Analysis of the interactions of Nrf-2, PMF-1, and CSN-7 with the 5'-flanking
      sequence of the mouse 4E-BP1 gene.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf-2) binds to a specific polyamine
      responsive element (PRE) in the promoter region of the spermidine-spermine
      acetyltransferase (SSAT) gene, a key component of the polyamine catabolic
      pathway. Regulation of SSAT gene transcription requires the additional
      interaction of Nrf-2 with polyamine modulated factor 1 (PMF-1). Likewise,
      transcription of the eukaryotic initiation factor 4E binding protein 1 (4E-BP1)
      gene is regulated in a polyamine-dependent manner, but the actual mechanism has
      not previously been determined. Analysis of the 5'-flanking sequence of the
      murine 4E-BP1 gene indicated the presence of several potential PRE sites, which
      might be involved in regulating its transcription. Our goal in this research was
      to determine potential interactions between Nrf-2, PMF-1, the human homologue of
      the Arabidopsis signalosome complex (CSN-7), and these potential PRE sites. Four
      PCR fragments containing regions with considerable homology (78%) to the human
      PRE were generated from the 5'-flanking sequence of the mouse 4E-BP1 gene and the
      fragments were used in electrophoretic gel mobility shift and supershift assays.
      Purified Nrf-2 interacted with all four of these fragments, and similar gel
      shifts were observed with both cytoplasmic and nuclear fractions of NIH-3T3
      cells. However, polyamine depletion with difluoromethylornithine (DFMO)
      eliminated the gel shift. Supershift assays indicated that the shift was due to
      the binding of Nrf-2, and the binding was competitive with a known Nrf-2 binding
      sequence. Purified PMF-1 did not bind any of the PCR fragments alone, but when
      added with Nrf-2, decreased the magnitude of the gel shift for one of the
      fragments (PRE located at -2060 relative to the transcription start site). CSN-7
      did not interact with the sequences, nor did it inhibit protein/DNA interaction.
      These data indicate a possible mechanism by which polyamines enhance the binding
      of a Nrf-2/PMF-1 complex to the 5'-flanking region of the 4E-BP1 gene. Since
      polyamines increase expression of the 4E-BP1 gene, it seems likely that formation
      of this complex is involved in its transcriptional regulation.

PMID- 16647091
TI  - Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium
      channel blocker, on myocardial apoptosis in ischemia-reperfusion injury.
AB  - The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel
      blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct
      size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45
      min/120 min) were investigated. Ten minutes prior to left coronary artery
      occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5
      mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced
      creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by
      DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end
      labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg)
      reduced infarct size significantly compared to vehicle group (18.75+/-0.65% and
      8.27+/-0.29% vs. 41.72+/-0.73%, P<0.01). Labedipinedilol-A also reduced the CK,
      CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition,
      labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from
      19.21+/-0.52% to 9.73+/-0.81% (P<0.01), which is consistent with absence of DNA
      ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment
      also decreased calcium content in ischemic-reperfused myocardial tissue. In
      conclusion, these results demonstrate that labedipindielol-A, through reduction
      of calcium overload and apoptosis, exerts anti-infarct effect during myocardial
      ischemia-reperfusion and would be useful clinically in the prevention of acute
      myocardial infarction.

PMID- 16647092
TI  - High levels of filamentous actin and apoptosis correlate with mast cell
      refractoriness under alloxan-evoked diabetes.
AB  - Mast cell number and reactivity were shown to be down-regulated under diabetic
      conditions. Since the balance between globular and filamentous actin plays a
      pivotal role in the activity of secretory cells, we investigated whether an
      imbalance in that system could underlie the hyporesponsiveness of mast cells in
      diabetes. The apoptotic state was also evaluated. By means of
      rhodamine/phalloidine staining of F-actin, we noted that diabetic mast cells
      exhibited an increase in fluorescence intensity and reduction in cellular size,
      when compared with cells from normal animals, in parallel with elevation in the
      percentage of cells developing apoptosis. The levels of Bax, a pro-apoptotic
      member of Bcl-2 family, appeared increased at baseline in mast cells from
      diabetic rats compared with normal cells. These phenomena correlated with
      reduction in histamine and PGD2 release following antigen challenge in vitro. The
      steroid antagonist RU 486 abolished the reduction of histamine secretion from
      diabetic mast cells. We conclude that hyporesponsiveness of mast cells noted in
      diabetes may be accounted for by reduction in actin filament plasticity, in clear
      association with the rise in the percentage of cells undergoing apoptosis. In
      addition, the refractoriness of diabetic mast cells to antigen in vitro seems to
      be dependent on glucocorticoids.

PMID- 16647093
TI  - Oral, post-oral and genetic interactions in sweet appetite.
AB  - Inbred mouse strains differ in their preferences for sweeteners, due in part to
      variations in their T1R3 sweet taste receptor. Recent studies of sweet sensitive
      C57BL/6J (B6) and subsensitive 129P3/J (129) mice indicate that experiential and
      post-oral effects of sugar substantially modify sweetener preference. In fact,
      the strain difference in sucrose preference disappeared after the mice were given
      23 h/day tests with sucrose at ascending concentrations (0.5-32%). Intragastric
      infusions of sucrose (16%) also conditioned increased preference for and absolute
      intake of flavored sweet solutions in B6 and 129 mice. An operant analysis of
      sweetener appetite revealed, unexpectedly, that sugar-experienced 129 mice
      respond more vigorously than B6 mice for 16% sucrose rewards. These findings
      indicate that experiential and nutritional factors can, to some degree, override
      genetic differences in peripheral taste sensitivity in determining food appetite.

PMID- 16647094
TI  - Variations in behavior, innate immunity and host resistance to B16F10 melanoma
      growth in mice that present social stable hierarchical ranks.
AB  - The present study analyzed the effect of social stable hierarchical
      dominance/submissive relationships in C57BL/6 mice on behavior, innate immunity,
      serum corticosterone levels and host resistance to B16F10 melanoma growth. Adult
      mice (90 days old) kept in pairs since weaning, were analyzed for
      dominant/submissive ranking in three consecutive days according to the presence
      or absence of fighting and/or anticipatory submissive responses. Only the pairs
      of mice where dominant/submissive relationships were clearly stated were
      employed. Results showed that submissive mice presented in relation to dominants:
      (1) decreased time spent in the central open-field area; (2) decreased number of
      entries into the open arms and decreased time spent in the exploration of the
      open arms of the plus maze; (3) increased time spent in exploration of the plus
      maze closed arms; (4) decreased number of entries and in the time spent in the
      exploration of the third part of the plus-maze open arms; (5) increased number of
      B16F10 metastasis in the lungs; (6) decreased NK cell cytotoxicity measured in
      vitro in the peripheral blood and spleen; (7) decreased basal but not in S.
      aureus induced oxidative burst in both neutrophils and monocytes and (8) similar
      basal serum levels of corticosterone. The present behavioral findings show that
      submissive mice, within a stable social hierarchy, present anxiety like-responses
      a fact that would make than more prone to stressful stimuli. This condition would
      be responsible for the decreases presently observed on basal neutrophil oxidative
      burst, NK cell activity and resistance to B16F10 tumor growth. Together the
      obtained data show that mice that present stable hierarchical relationships
      display neuro-immune alterations comparable to those reported in mice under a
      situation of chronic social stress.

PMID- 16647095
TI  - Responses of well-differentiated nasal epithelial cells exposed to particles:
      role of the epithelium in airway inflammation.
AB  - Numerous epidemiological studies support the contention that ambient air
      pollution particles can adversely affect human health. To explain the acute
      inflammatory process in airways exposed to particles, a number of in vitro
      studies have been performed on cells grown submerged on plastic and poorly
      differentiated, and on cell lines, the physiology of which is somewhat different
      from that of well-differentiated cells. In order to obtain results using a model
      system in which epithelial cells are similar to those of the human airway in
      vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells
      cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust
      particles (DEP) and Paris urban air particles (PM(2.5)). DEP and PM(2.5) (10-80
      microg/cm(2)) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion
      exclusively towards the basal compartment. In contrast, there was no IL-1beta
      secretion and only weak non-reproducible secretion of TNF-alpha. IL-6 and GM-CSF
      were consistently stimulated towards the apical compartment and only when cells
      were exposed to PM(2.5). ICAM-1 protein expression on cell surfaces remained low
      after particle exposure, although it increased after TNF-alpha treatment.
      Internalization of particles, which is believed to initiate oxidative stress and
      proinflammatory cytokine expression, was restricted to small nanoparticles (< or
      =40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were
      more efficient than PM(2.5). Collectively, our results suggest that airway
      epithelial cells exposed to particles augment the local inflammatory response in
      the lung but cannot alone initiate a systemic inflammatory response.

PMID- 16647096
TI  - Structure of the envelope protein domain III of Omsk hemorrhagic fever virus.
AB  - We have solved the NMR solution structure of domain III from the Omsk hemorrhagic
      fever virus envelope protein and report the first sequencing of the Guriev strain
      of this virus. Important structural differences between tick-borne flaviviruses,
      such as OHFV and TBE, and mosquito-borne flaviviruses, such as West Nile virus,
      are discussed.

PMID- 16647097
TI  - KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity.
AB  - Pim kinases are proto-oncogenes that are upregulated in a number of B cell
      cancers, including Epstein-Barr Virus (EBV) associated Burkitt's lymphoma. They
      have also been shown to be upregulated in Kaposi sarcoma-associated herpes virus
      (KSHV) infected primary B cells. Most cells in KSHV-associated tumors are
      latently infected and express only a small subset of viral genes, with KSHV
      latency associated nuclear antigen (LANA) being constitutively expressed. LANA
      regulates the transcription of a large number of cellular and viral genes. Here,
      we show that LANA upregulates transcription from the Pim-1 promoter (pPim-1) and
      map this activation to a region in the promoter located within the sequence (-681
      to +37). We show that LANA expressing cells can proliferate faster and are better
      protected from drug induced apoptosis. Since transition through cell cycle check
      points and anti-apoptosis are functions associated with Pim-1, it is likely that
      higher Pim-1 expression in cells expressing LANA is responsible, at least in
      part, for this effect. A Pim-1 phosphorylation site was also identified within
      the amino-terminal domain of LANA. Using in vitro kinase assays, we confirmed
      that LANA was indeed a Pim-1 substrate, and the failure of Pim-1 to phosphorylate
      LANA mutated at SS205/6RR identified this site as the specific serine residues
      phosphorylated by Pim-1. This report provides valuable insight into yet another
      cellular signaling pathway subverted by KSHV LANA and suggests a contribution to
      KSHV related oncogenesis.

PMID- 16647098
TI  - A dominant-negative effect of cynomolgus monkey tripartite motif protein
      TRIM5alpha on anti-simian immunodeficiency virus SIVmac activity of an African
      green monkey orthologue.
AB  - African green monkey (AGM) tripartite motif protein (TRIM) 5alpha can inhibit
      both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency
      virus SIVmac, whereas cynomolgus monkey (CM) TRIM5alpha can inhibit HIV-1, but
      not SIVmac. We previously reported that the 17-amino-acid region and an adjacent
      20-amino-acid duplication in the SPRY(B30.2) domain of AGM TRIM5alpha determined
      the species specificity. In the present study, we demonstrated that CM TRIM5alpha
      had a dominant-negative effect on the anti-SIVmac activity of AGM TRIM5alpha. In
      contrast, mutant TRIM5alphas lacking the 20-amino-acid duplication did not have
      the dominant-negative effect, even though they failed to restrict SIVmac. These
      results indicated that oligomerization of the SPRY domain is required for anti
      SIVmac activity and suggest that tight interaction between the viral capsid and
      all three molecules in one TRIM5alpha trimer may not be necessary for restriction
      activity.

PMID- 16647099
TI  - Evaluation of replicative capacity and genetic stability of West Nile virus
      replicons using highly efficient packaging cell lines.
AB  - A stable cell system for high-efficiency packaging of West Nile virus (WNV)
      subgenomic replicons into virus-like particles (VLPs) was developed. VLPs could
      be propagated on these packaging cells and produced infectious foci similar to
      foci produced by WNV. Focus size correlated with the replicative capacity of WNV
      replicons, indicating that genome copy number, rather than amount of trans
      complementing structural proteins, was rate-limiting in packaging of VLPs.
      Comparison of VLP production from replicon genomes encoding partial or complete C
      genes indicated that portions of C downstream of the cyclization sequence could
      improve genome replication or that cis expression of C could enhance packaging.
      Interestingly, a rapid loss of replicon-encoded reporter gene activity was
      detected within two serial passages of reporter gene-containing VLPs. The loss of
      reporter activity correlated with gene deletion and better VLP growth, indicating
      a powerful selection pressure for WNV genomes lacking reporter genes.

PMID- 16647100
TI  - Dechlorination/hydrogenation and destruction reactions of PCDDs in OCDD-added fly
      ash heated under vacuum.
AB  - Octachlorodibenzo-p-dioxin (OCDD)-added, pretreated fly ash was heated under
      vacuum at sample temperatures ranging from T(s)=450 to 650 K. The fly ash and
      liquid nitrogen-cooled trap samples were analyzed for DD/DF through OCDD/DF. The
      total amounts of DD through OCDD decrease with increasing T(s), which indicates
      that dechlorination/hydrogenation (DCH) reactions are not the only reaction
      channels. Reduction of toxic equivalent (TEQ) for PCDDs by more than 99% was
      achieved in the fly ash by the vacuum heat treatment at T(s)=650 K for 4 h. The
      total amount of PCDDs and DD detected in the liquid nitrogen-cooled trap relative
      to that of added OCDD was about 17%, i.e., PCDDs and DD which were adsorbed to
      the fly ash surfaces can evaporate into the gaseous phase. The difference between
      the evaporation behavior of PCDDs in the present and the previous studies is
      discussed in the light of their states of existence.

PMID- 16647101
TI  - Dissolution of resin acids, retene and wood sterols from contaminated lake
      sediments.
AB  - The dissolution potency of hydrophobic resin acids (RAs), retene and wood sterols
      from sediments was studied. These wood extractives and their metabolites are
      sorbed from pulp and paper mill effluents to downstream sediments. With harmful
      components like these, sediments can pose a hazard to the aquatic environment.
      Therefore, sediment elutriates with water were produced under variable conditions
      (agitation rate and efficiency, time), and concentrations of the dissoluted
      compounds were analyzed. Both naturally contaminated field sediments and
      artificially spiked sediments were studied. By vigorous agitation RAs can be
      released fast from the sediment matrix and equilibrium reached within 3 days.
      Compared to RAs, desorption of retene from lake sediment was slower and did not
      completely reach equilibrium in 23 days. Sterols spiked to pristine sediment with
      a 33-day contact time desorbed faster than those associated authentically with
      industrial sediment of from a contaminated lake. Simulating the water turbulence
      adjacent to a sediment surface by low and high rate of agitation in the
      laboratory, an increase in the mixing rate after 43-day elutriation suddenly
      released a high amount of wood sterols. The results indicate wide variation
      between hazardous chemicals in their tendency to dissolution from sediment
      solids. Erosion and hydrology adjacent to the sediment surface, as well as risks
      from dredging activities of sediments, may expose lake biota to bioactive
      chemicals.

PMID- 16647102
TI  - Using economic valuation techniques to inform water resources management: a
      survey and critical appraisal of available techniques and an application.
AB  - The need for economic analysis for the design and implementation of efficient
      water resources management policies is well documented in the economics
      literature. This need is also emphasised in the European Union's recent Water
      Framework Directive (2000/60/EC), and is relevant to the objectives of Euro
      limpacs, an EU funded project which inter alia, aims to provide a decision
      support system for valuing the effects of future global change on Europe's
      freshwater ecosystems. The purpose of this paper is to define the role of
      economic valuation techniques in assisting in the design of efficient, equitable
      and sustainable policies for water resources management in the face of
      environmental problems such as pollution, intensive land use in agriculture and
      climate change. The paper begins with a discussion of the conceptual economic
      framework that can be used to inform water policy-making. An inventory of the
      available economic valuation methods is presented and the scope and suitability
      of each for studying various aspects of water resources are critically discussed.
      Recent studies that apply these methods to water resources are reviewed. Finally,
      an application of one of the economic valuation methods, namely the contingent
      valuation method, is presented using a case study of the Cheimaditida wetland in
      Greece.

PMID- 16647103
TI  - C4 plant isotopic composition (delta13C) evidence for urban CO2 pollution in the
      city of Cotonou, Benin (West Africa).
AB  - The carbon isotopic composition (delta13C) of plants can reveal the isotopic
      carbon content of the atmosphere in which they develop. The delta13C values of
      air and plants depend on the amount of atmospheric fossil fuel CO2, which is
      chiefly emitted in urban areas. A new indicator of CO2 pollution is tested using
      the delta13C variation in a C4 grass: Eleusine indica. A range of about 4 per
      thousand delta units was observed at different sites in Cotonou, the largest city
      in the Republic of Benin. The highest delta13C values, from -12 per thousand to 
      14 per thousand, were found in low traffic zones; low delta13C values, from -14
      per thousand to -16 per thousand, were found in high traffic zones. The amount of
      fossil fuel carbon assimilated by plants represented about 20% of the total plant
      carbon content. An overall decrease in plant delta13C values was observed over a
      four-year monitoring period. This decrease was correlated with increasing vehicle
      traffic. The delta13C dataset and the corresponding geographical database were
      used to map and define zones of high and low 13C-depleted CO2 emissions in urban
      and sub-urban areas. The spatial distribution follows dominant wind directions,
      with the lowest emission zones found in the southwest of Cotonou. High CO2
      emissions occurred in the north, the east and the center, providing evidence of
      intense anthropogenic activity related to industry and transportation.

PMID- 16647104
TI  - Climate-change impacts on hydrology and nutrients in a Danish lowland river
      basin.
AB  - The Mike 11-TRANS modelling system was applied to the lowland Gjern river basin
      in Denmark to assess climate-change impacts on hydrology and nitrogen retention
      processes in watercourses, lakes and riparian wetlands. Nutrient losses from land
      to surface waters were assessed using statistical models incorporating the effect
      of changed hydrology. Climate-change was predicted by the ECHAM4/OPYC General
      Circulation Model (IPCC A2 scenario) dynamically downscaled by the Danish HIRHAM
      regional climate model (25 km grid) for two time slices: 1961-1990 (control) and
      2071-2100 (scenario). HIRHAM predicts an increase in mean annual precipitation of
      47 mm (5%) and an increase in mean annual air temperature of 3.2 degrees C (43%).
      The HIRHAM predictions were used as external forcings to the rainfall-runoff
      model NAM, which was set up and run for 6 subcatchments within and for the
      entire, Gjern river basin. Mean annual runoff from the river basin increases 27
      mm (7.5%, p<0.05) when comparing the scenario to the control. Larger changes,
      however, were found regarding the extremes; runoff during the wettest year in the
      30-year period increased by 58 mm (12.3%). The seasonal pattern is expected to
      change with significantly higher runoff during winter. Summer runoff is expected
      to increase in predominantly groundwater fed streams and decrease in streams with
      a low base-flow index. The modelled change in the seasonal hydrological pattern
      is most pronounced in first- or second-order streams draining loamy catchments,
      which currently have a low base-flow during the summer period. Reductions of 40
      70% in summer runoff are predicted for this stream type. A statistical nutrient
      loss model was developed for simulating the impact of changed hydrology on
      diffuse nutrient losses (i.e. losses from land to surface waters) and applied to
      the river basin. The simulated mean annual changes in TN loads in a loamy and a
      sandy subcatchment were, respectively, +2.3 kg N ha(-1) (8.5%) and +1.6 kg N ha(
      1) (6.9%). The rainfall-runoff model and the nutrient loss model were chained
      with Mike 11-TRANS to simulate the combined effects of climate-change on
      hydrology, nutrient losses and nitrogen retention processes at the scale of the
      river basin. The mean annual TN export from the river basin increased from the
      control to the scenario period by 7.7%. Even though an increase in nitrogen
      retention in the river system of 4.2% was simulated in the scenario period, an
      increased in-stream TN export resulted because of the simulated increase in the
      diffuse TN transfer from the land to the surface-waters.

PMID- 16647105
TI  - Identification of chromosomal alterations important in the development of
      cervical intraepithelial neoplasia and invasive carcinoma using alignment of DNA
      microarray data.
AB  - OBJECTIVE: To use microarray data to reveal regions of potential chromosomal loss
      or gain important in cervical intraepithelial neoplasia (CIN) and invasive
      cervical cancer by identifying mRNA expression biases in contiguous chromosomal
      regions. METHODS: Data from three RNA expression microarray experiments were
      used: one primary experiment using cDNA arrays profiling gene expression in
      cervical epithelium from viral cytopathic effect to invasive cancer, one
      experiment using Affymetrix arrays profiling gene expression in invasive
      cancerous cervical epithelium, and one experiment using Affymetrix arrays
      profiling gene expression in CIN cervical biopsy specimens. Gene expression was
      aligned along chromosomes to reveal regions of significant chromosomal imbalance.
      Regions showing significant gain or loss and verified in more than one experiment
      are presented here. RT-PCR was performed to validate expression of one gene in a
      region. RESULTS: Gain of 3q was detected from the CIN II (P=0.018), CIN III
      (P=0.005), and invasive cancer (P=0.0002) cDNA arrays, and gain of 12q was
      detected from the CIN (P=0.05) and invasive cancer (P=0.05) Affymetrix arrays.
      Loss of 6p was detected from the CIN III (P=0.004) cDNA arrays and invasive
      cancer (P=0.05) Affymetrix arrays. Loss of 4q was detected from the invasive
      cancer (P=0.04) cDNA arrays and invasive cancer (P=0.05) Affymetrix arrays. RAN,
      located in the region of gain on 12q24.3, was overexpressed in CIN and invasive
      cancer. CONCLUSIONS: Alignment of microarray expression data by chromosomes can
      be used to estimate regions of potential chromosomal aberration and identify
      differentially expressed genes important in the development of CIN and invasive
      cancer.

PMID- 16647106
TI  - Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer.
AB  - OBJECTIVE: To report the utility of the monoclonal, anti-vascular endothelial
      growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for
      women with recurrent cervical cancer. METHODS: A retrospective analysis of women
      with recurrent cervical cancer treated with bevacizumab combination therapy was
      performed. RESULTS: Six patients were identified. The patients had a median of 3
      prior regimens. All of the patients had multisite, metastatic disease. The
      combination regimen included IV 5-fluorouracil in 5 (83%) patients and
      capecitabine in one (17%) subject. Treatment was well tolerated. Grade 4 toxicity
      occurred in one patient who developed neutropenic sepsis. Clinical benefit (CR,
      PR, or SD) was noted in 67% of the subjects. This included 1 (17%) complete
      response, 1 (17%) partial response and two (33%) patients with stable disease.
      The median time to progression for the four women who demonstrated clinical
      benefit was 4.3 months. CONCLUSIONS: Combination bevacizumab is well tolerated
      and displayed encouraging anti-tumor activity in heavily pretreated recurrent
      cervical cancer.

PMID- 16647107
TI  - Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine
      withdrawal in the rat.
AB  - Withdrawal from psychostimulants, including methamphetamine, induces a depressive
      state associated with lethargy, dysphoria, hyperphagia and psychomotor
      retardation. Previous work with repeated administration of amphetamine in rats
      has shown that amphetamine withdrawal produces decreased motivation to work for a
      non-drug reward, and this withdrawal is reversed by administration of a dopamine
      partial agonist. The purpose of the present study was to examine decreased
      motivation to work for a non-drug reward during methamphetamine withdrawal and
      explore the effects of a dopamine agonist, dopamine partial agonist, and indirect
      monoamine agonist on methamphetamine withdrawal. During withdrawal from repeated
      methamphetamine administration, rats showed reduced responding for a sweet
      solution in a progressive-ratio schedule of reinforcement, and this effect was
      significantly more pronounced than previously observed with amphetamine. Repeated
      systemic treatment with the dopamine partial agonist terguride (0.2 and 0.4
      mg/kg, i.p., twice daily), the full dopamine agonist ropinirole (1 mg/kg, i.p.,
      twice daily), and acetyl-L-carnitine (60 and 100 mg/kg, i.p.), a compound with a
      potential antidepressant effect, during methamphetamine withdrawal restored
      responding for the sweet solution, suggesting that these drugs may represent
      potential therapeutic strategies for the treatment of methamphetamine addiction
      during the withdrawal phase.

PMID- 16647108
TI  - Locomotion is the major determinant of sibutramine-induced increase in energy
      expenditure.
AB  - The anti-obesity effect of the serotonin and noradrenaline reuptake inhibitor
      sibutramine has been attributed to a dual mechanism involving a reduction of food
      intake and an increase in energy expenditure. This dual action increases the
      possibilities for induction of a negative energy balance, the principal goal of
      an anti-obesity treatment. To elucidate the mechanism behind sibutramine-induced
      increase in energy expenditure, we applied indirect calorimetry combined with
      monitoring locomotor activity and body temperature. We confirm that sibutramine
      has both anorectic and thermogenic effects. In addition, we show here that
      sibutramine also causes a dose-dependent increase in locomotor activity (LMA) of
      rats, occurring in parallel with increase in energy expenditure. The dose of
      sibutramine necessary to induce an effect on locomotion and energy expenditure
      was only marginally higher than the dose sufficient to induce a significant
      reduction of food intake. The relation between LMA and energy expenditure was
      similar to that found with d-amphetamine, which causes both hyper-locomotion and
      increased energy expenditure, but was different from 2,4-dinitrophenol which
      causes increase in energy expenditure but not in locomotion. The effect of
      sibutramine (20 mg/kg) on energy expenditure was not inhibited by the non
      selective 5-HT receptor antagonist, metergoline (1 mg/kg), or a high dose (20
      mg/kg) of the non-selective beta-blocker propranolol, but was blocked by D1
      dopamine receptor inhibitor SCH 23390 (0.3 mg/kg). Therefore, we conclude that
      the effect of sibutramine on energy expenditure in rats is predominantly due to a
      dopamine-dependent increase in locomotor activity.

PMID- 16647109
TI  - Role of TRPV1 and cannabinoid CB1 receptors in AM 404-evoked hypothermia in rats.
AB  - AM 404 inhibits endocannabinoid uptake and enhances the cannabinoid CB(1)
      mediated effects of endogenous cannabinoids. Accumulating evidence also suggests
      that AM 404 acts at sites other than the endocannabinoid system. One site is the
      transient receptor potential vanilloid 1 cation channel (TRPV1). A useful
      endpoint for discriminating between TRPV1- or CB(1)-mediated effects of AM 404 is
      hypothermia. This is because TRPV1 or CB(1) receptor activation produces a
      significant hypothermia in rats. The present study investigated the effects of AM
      404 (1, 5, 10 and 20 mg/kg, i.p.) on body temperature in rats and the involvement
      of TRPV1 and CB(1) receptors in the effects of AM 404. Doses of 10 and 20 mg/kg
      of AM 404 produced significant hypothermia. Pre-treatment with capsazepine (30
      mg/kg, i.p.) blocked the hypothermia caused by 10 and 20 mg/kg of AM 404. Pre
      treatment with SB 366791 (2 mg/kg, i.p.), a new TRPV1 antagonist, also abolished
      the hypothermia evoked by AM 404 (20 mg/kg, i.p.). In contrast, pre-treatment
      with SR 141716A (Rimonabant), a CB(1) antagonist, or AA-5-HT, a fatty acid amide
      hydrolase (FAAH) blocker, did not affect AM 404-evoked hypothermia. The present
      data demonstrate that AM 404 evokes a significant hypothermia in rats that is
      dependent on TRPV1 receptor activation.

PMID- 16647110
TI  - A pharmacological map of the PI3-K family defines a role for p110alpha in insulin
      signaling.
AB  - Phosphoinositide 3-kinases (PI3-Ks) are an important emerging class of drug
      targets, but the unique roles of PI3-K isoforms remain poorly defined. We
      describe here an approach to pharmacologically interrogate the PI3-K family. A
      chemically diverse panel of PI3-K inhibitors was synthesized, and their target
      selectivity was biochemically enumerated, revealing cryptic homologies across
      targets and chemotypes. Crystal structures of three inhibitors bound to p110gamma
      identify a conformationally mobile region that is uniquely exploited by selective
      compounds. This chemical array was then used to define the PI3-K isoforms
      required for insulin signaling. We find that p110alpha is the primary insulin
      responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a
      phenotypic threshold for p110alpha activity. Compounds targeting p110alpha block
      the acute effects of insulin treatment in vivo, whereas a p110beta inhibitor has
      no effect. These results illustrate systematic target validation using a matrix
      of inhibitors that span a protein family.

PMID- 16647111
TI  - Influence of the dam and sire on size at birth and subsequent growth, milk
      production and fertility in dairy heifers.
AB  - Genetic selection has resulted in larger cows with high milk production potential
      but a tendency for poor fertility. In multiparous cows fetal development competes
      for nutrients with concurrent milk production. This study tested the hypotheses
      that (a) maternal age and milk yield during pregnancy alter calf birth size and
      (b) birth weight influences subsequent productivity and fertility. Concurrently
      born Holstein-Friesian heifers (n=65) with multiparous dams and three sires were
      monitored from birth to the end of their first lactation to assess effects of
      birth weight on growth, milk production and fertility. Calves were analyzed as
      three subgroups: low (L), average (A) and high (H) birth weight (BW) calves (n=21
      22 per group). LBW calves were born 10 kg lighter than HBW calves and remained
      significantly lighter throughout the study. They were generally smaller in other
      measured indices (length, height, girth, ponderal index) between birth and 9
      months and were more likely to have older dams (lactations 3-6) with higher peak
      yields (>42 kg/day). Milk production parameters were indistinguishable between
      the 3 birthweight groups and metabolic parameters (IGF-I, insulin, glucose)
      measured around first calving were unaffected. HBW offspring were more likely to
      have persistent corpora lutea following their first calving and other fertility
      parameters also tended to be worse. Sire influenced gestation length but not
      birth size. Sire heritability estimates showed that weight, IGF-I and insulin
      concentrations after first calving and fertility in the first lactation were all
      heritable. The results support the hypothesis that high milk production in the
      dam may predispose to birth of a smaller calf. Smaller birth size did not,
      however, have any subsequent adverse effects on productivity or fertility in the
      first lactation and sire was more influential at this stage.

PMID- 16647112
TI  - Piezoelectric properties of human dentin and some influencing factors.
AB  - OBJECTIVES: The present study focused on the piezoelectricity of human dentin.
      The effects of moisture content and orientation of tubules were investigated.
      METHODS: Fresh human dentin was cut with two surfaces generally parallel to the
      occlusal surface. The potentials generated by specimens were detected, as the
      compression loads were respectively parallel and vertical to the tubules.
      Moreover, specimens were dried and rehydrated; piezoelectric coefficients d(33)
      of dentin with different moisture content were measured horizontally to, and
      vertically to, the tubules. RESULTS: The results showed that piezoelectricity of
      dentin increased with increasing moisture content. Furthermore, greater
      piezoelectricity was detected parallel to the tubules than vertical to the
      tubules. SIGNIFICANCES: This study indicated that the piezoelectric properties of
      dentin were significantly affected by both humidity and orientation of the
      tubules. Both structural and free water in dentin is attributed to its
      piezoelectric properties.

PMID- 16647113
TI  - A defined system to allow skeletal muscle differentiation and subsequent
      integration with silicon microstructures.
AB  - This work documents the development of an in vitro cell culture model consisting
      of a novel serum-free medium and a non-biological growth substrate, N-1[3
      (trimethoxysilyl) propyl] diethylenetriamine (DETA), to enable functional myotube
      integration with cantilevers fabricated using MEMS technology. This newly
      developed, defined in vitro model was used to study the differentiation of fetal
      rat skeletal muscle and it promoted the formation of myotubes from the
      dissociated rat fetal muscle cells. The myotubes were characterized by
      morphological analysis, immunocytochemistry and electrophysiology. Further, it
      was demonstrated that when the dissociated muscle cells were plated on fabricated
      microcantilevers, the muscle cells aligned along the major axis of the cantilever
      and formed robust myotubes. This novel system could not only find applications in
      skeletal muscle differentiation and biocompatibility studies but also in
      bioartificial muscle engineering, hybrid actuation system development,
      biorobotics and for a better understanding of myopathies and neuromuscular
      disorders.

PMID- 16647114
TI  - Comparison of standard surface chemistries for culturing mesenchymal stem cells
      prior to neural differentiation.
AB  - A critical element of any stem cell differentiation protocol is the ability to
      compare its effects relative to an undifferentiated population of the same cells.
      In an attempt to standardize pre-differentiation conditions of adult derived
      mesenchymal stem cells prior to neural induction experiments, we asked what is
      the simplest chemical surface that supports the growth and maintenance of these
      cells in a pre-differentiation state. Adult bone marrow-derived rat mesenchymal
      stem cells (BMSCs) were expanded in vitro on Permanox Lab-Tek tissue culture
      treated plastic (TCP), poly-D-lysine (PDL) coated glass, PDL-laminin-1 coated
      glass, and untreated glass. TCP provided the best surface for maintaining
      morphologies generally considered to be undifferentiated, while PDL coated glass
      and uncoated glass provided the least suitable surfaces. Expansion of BMSCs on
      PDL-laminin-1 coated glass resulted in expression of nestin, a marker associated
      with neuronal and other progenitor cells, and therefore may confound experimental
      results if used as a pre-differentiation surface.

PMID- 16647115
TI  - Stem cell attachment to layer-by-layer assembled TiO2 nanoparticle thin films.
AB  - Surface topography is one of the most important factors influencing the
      attachment and spreading of cells. In the present study, layer-by-layer assembled
      titanium dioxide (TiO2) nanoparticle thin films were chosen for attachment,
      proliferation and spreading studies on mouse mesenchymal stem cells (MSC).
      Increasing surface roughness was observed with increasing number of layer-by
      layer assembled TiO2 thin films. Four layer TiO2 thin film showed higher number
      of attached cells than a one layer thin film and control surfaces. MSCs
      experienced no cytotoxic effects after culture on the TiO2 coated substrates as
      observed from the cytotoxicity tests. Cell spreading, visualized with scanning
      electron microscopy, showed a faster rate of spreading on a rougher surface.
      Cells on a four-layer substrate, at 12 h showed complete spreading, where as most
      of the cells on a control surface and a one-layer surface, at 24 h, retained a
      rounded morphology. In conclusion, TiO2 nanoparticle thin films were successfully
      assembled in alternation with polyelectrolytes and in-vitro studies with MSC
      showed an increase in the attachment and faster spreading of cells on rougher
      surfaces.

PMID- 16647116
TI  - Homeobox genes are differentially expressed in macrovascular human umbilical vein
      endothelial cells and microvascular placental endothelial cells.
AB  - Angiogenesis is fundamental to normal placental development. Aberrant
      angiogenesis within the placental terminal villi is a characteristic of
      significant placental pathologies and includes structural and vascular
      abnormalities as well as altered endothelial cell function, which substantially
      impacts on maternal-fetal exchange. Homeobox gene transcription factors regulate
      vascular development in embryonic and adult tissues, but their role in the
      placental microvasculature is not well known. In this study, we isolated and
      enriched human placental microvascular endothelial cells (PLEC) by a perfusion
      based method and compared homeobox gene expression between PLEC and macrovascular
      human umbilical vein endothelial cells (HUVEC). Reverse transcriptase PCR
      detected mRNA expression of homeobox genes DLX3, DLX4, MSX2, GAX and HLX1 in both
      PLEC and HUVEC. DLX4 and HLX1 have not been previously detected in PLEC and with
      the exception of GAX, none of these homeobox genes have been previously
      identified in HUVEC. There was lower expression of HLX1 mRNA in HUVEC compared
      with PLEC. Using real-time PCR analysis PLEC HLX1 mRNA expression relative to
      housekeeping gene GAPDH was 0.9+/-0.06 fold of the calibrator (n=6) versus 0.2+/
      0.06 (n=6) for HUVEC, p<0.001. These data provided evidence of heterogeneity in
      homeobox gene expression between microvascular PLEC and macrovascular HUVEC that
      most likely reflects significant differences in endothelial cell function in the
      two different cellular environments.

PMID- 16647117
TI  - Micronuclei induction and chromosomal aberrations in Rattus norvegicus by
      chloroacetic acid and chlorobenzene.
AB  - Chloroacetic acid (CAA) and chlorobenzene (CB) have been evaluated for in vivo
      mutagenic potential in Rattus norvegicus, employing the following criteria : (i)
      chromosomal aberrations (CAs) such as breaks, gaps, exchanges, rings, and
      multiple aberrations and (ii) micronuclei (MN) induction. Three sublethal doses,
      0.008, 0.01, and 0.012 mg/g b. wt. of CAA and 0.75, 1.0, and 1.25 mg/g b. wt. of
      rat of CB were administered and the bone marrow cells evaluated in each of the
      three treated groups at 12, 24, and 48 h, respectively. Mean MN frequencies of
      4.40+/-0.2 and 5.42+/-0.3, obtained respectively for CAA and CB. The higher
      induction of MN by CAA and CB was dose- and time-dependent. Most significant
      impact (P<0.05) for either of the compounds was observed at 24h post
      administration, when the recorded mean frequency of CAs was maximum for CAA
      (4.33+/-0.6) as well as for CB (4.66+/-0.5).

PMID- 16647118
TI  - Determinations of dioxinlike activity in selected mollusks from the coast of the
      Bohai Sea, China, using the H4IIE-luc bioassay.
AB  - Extracts of mollusks collected from eight cities along the coast of the Bohai
      Sea, China, were used to determine dioxinlike activity using an in vitro bioassay
      approach. Dioxinlike activity of total extracts was detected by measuring
      luciferase activity in a stable transfected rat hepatoma cell line, H4IIE,
      containing an aryl hydrocarbon receptor (AhR)-responsive element linked to a
      luciferase reporter gene. Luciferase activity was expressed as a percentage of
      the maximum response observed for 2,3,7,8-TCDD (% TCDD(max)). All mollusk samples
      elicited significant dioxinlike activity except those from Dalian (N1). The
      greatest magnitudes (+/-SD, data ex N1) of activity observed for these extracts
      ranged from 4.88+/-0.48% to 11.38+/-1.43% TCDD(max). The mean activity was 7.37+/
      1.85% TCDD(max). Concentrations of TCDD-EQs in mollusk extracts were from 227.4
      to 547.5 pg g(-1) lipid. The cytotoxic effect of the mollusk extracts on cells
      was assessed at the same time. Six of the mollusk extracts (N2, N3, N4, S1, S2,
      and S4) caused noticeable growth inhibition over the exposure period at
      concentrations higher than 0.33% of the extracts concentrations (0.83 microL
      extract well(-1)). All the dilutions of sample N1 were cytotoxic to the H4IIE
      cells.

PMID- 16647119
TI  - Development and biological properties of a new live attenuated mumps vaccine.
AB  - To develop a new live attenuated mumps vaccine, a wild mumps Y7 strain isolated
      from a patient who developed mild parotitis was treated with nitrosoguanidine and
      ultraviolet, followed by selection of a temperature-sensitive clone. The selected
      clone, Y125, showed stable temperature-sensitivity in Vero cells. Intraspinal
      inoculation of marmosets with the Y125 produced only minimal histopathological
      changes, while intracerebral inoculation of neonatal rats revealed that the Y125
      did not cause hydrocephalus. Both these effects of the Y125 were similar to those
      of the non-neurovirulent Jeryl Lynn strain. Furthermore, subcutaneous inoculation
      of the Y125 induced high levels of neutralizing antibodies in all Cercopithecus
      monkeys examined. Although the safety and immunogenicity should be confirmed in
      further field trials in humans, the present results indicate that the Y125 could
      be a promising vaccine candidate.

PMID- 16647120
TI  - Looking for a general for some modern major models.
AB  - Computer climate models are some of the most complex scientific structures ever
      conceived. Consisting of hundreds of thousands of equations and running on
      supercomputers capable of trillions of operations per second, they chart the
      evolution of past and future climates across thousands of years. These
      simulations are breathtaking in their qualitative detail and vastly ambitious in
      their quantitative exactitude. However, their progress has recently been
      challenged by the very size and complexity of the models, factors that are also
      paralleled in the communities of scientists that build them. This complex co
      evolution of computers and scientific communities gives us insight into the
      promise and limits of sciences driven by exponential increases in computing
      power.

PMID- 16647121
TI  - Mapping of the regions on the heavy chain of botulinum neurotoxin A (BoNT/A)
      recognized by antibodies of cervical dystonia patients with immunoresistance to
      BoNT/A.
AB  - The purpose of this work was to map the entire recognition profile of the H chain
      of botulinum neurotoxin A (BoNT/A) by Abs in sera that have protective anti
      BoNT/A Abs by the mouse protection assay (MPA) from cervical dystonia (CD)
      patients who had been treated with botulinum neurotoxin, serotype A (BOTOX). In
      previous studies we found that human anti-tetanus neurotoxin (TeNT) Abs cross
      react with BoNT/A and BoNT/B. In the present work we devised an assay procedure
      for measuring specific anti-BoNT/A Abs in human sera by absorbing out or
      inhibiting the anti-TeNT Abs with TeNT before analyzing the sera for the anti
      BoNT/A Abs. The sera were obtained from 28 CD patients who had become
      unresponsive to treatment with BoNT/A and the sera were found to protect mice
      against a lethal dose of BoNT/A. For localization of the Ab-binding regions on
      the H chain we employed a set of sixty, 19-residue synthetic peptides (except for
      peptide C31 which was 22 residues) that encompassed the entire H chain sequence
      449-1296 and overlapped consecutively by five residues. The pattern of Ab
      recognition varied from patient to patient, but a very limited set of peptides
      were recognized by most of the patients. These were, in decreasing amounts of Ab
      binding, peptide N25 (H chain residues 785-803), C9/C10 (967-985/981-999), C31
      (1275-1296), C15 (1051-1069), C20 (1121-1139), N16 (659-677), N22 (743-761), and
      N4 (491-509). But not every serum recognized all these peptides. The finding that
      the binding profile was not the same for all the patients is consistent with
      previous observations that immune responses to protein antigens are under genetic
      control and that the response to each epitope within a protein is under separate
      genetic control. Except for the region within C9/C10, the other regions either
      coincided (N16 and C31), or overlapped (N4, N22, N25, C15 and C20), with the
      recently mapped synaptosomes (snps)-binding regions on the H chain. The molecular
      and clinical implications of these findings are discussed.

PMID- 16647122
TI  - Short-term course of intraocular pressure after intravitreal injection of
      triamcinolone acetonide.
AB  - OBJECTIVE: To describe the natural history of intraocular pressure (IOP) within
      the first 30 minutes after intravitreal injection of triamcinolone acetonide
      (TA). DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS:
      Thirty-eight consecutive patients who met inclusion and exclusion criteria and
      underwent intravitreal injection of 0.1 ml (4 mg) of TA were studied. METHODS:
      Intraocular pressure was measured by Goldmann applanation tonometry at baseline;
      immediately after injection; and at 2, 5, 10, 20, and 30 minutes after injection.
      MAIN OUTCOME MEASURES: Intraocular pressure measurements at baseline; immediately
      after intravitreal injection; and 2, 5, 10, 20, and 30 minutes after injection,
      and percentage of patients with IOP < or = 24 mmHg at 30 minutes. RESULTS:
      Patients who did not experience vitreous reflux (30/38 [78.9%]) at the site of
      injection had a significant initial elevation of IOP that rapidly normalized.
      Patients who experienced vitreous reflux (8/38 [21.1%]) at the site of injection
      had either no change in IOP or a small drop in IOP that rapidly normalized. The
      IOP measured in millimeters of mercury immediately after injection (45.9 [no
      reflux], 12.6 [reflux]), 2 minutes after injection (39.9 [no reflux], 13.5
      [reflux]), 5 minutes after injection (33.3 [no reflux], 13.8 [reflux]), 10
      minutes after injection (26.4 [no reflux], 15.1 [reflux]), and 20 minutes after
      injection (21.8 [no reflux], 15.0 [reflux]) showed a statistically significant
      difference between the 2 groups. The difference in IOP between the 2 groups was
      not significant at baseline or 30 minutes after injection. At 30 minutes, 90%
      (95% confidence interval, 85.8%-95.2%) of patients without vitreous reflux had an
      IOP < 24 mmHg. CONCLUSIONS: Patients undergoing intravitreal injection of TA with
      no vitreous reflux have a risk of short-term elevation of IOP that rapidly
      normalizes over 30 minutes. In patients with vitreous reflux after the injection,
      the IOP declines immediately after injection and rapidly normalizes over 10
      minutes.

PMID- 16647123
TI  - Automated detection of clinically significant macular edema by grid scanning
      optical coherence tomography.
AB  - OBJECTIVE: To compare the detection of clinically significant diabetic macular
      edema (DME) by an optical coherence tomography (OCT) grid scanning protocol and
      biomicroscopic examination. DESIGN: Retrospective case series. PARTICIPANTS:
      Outpatients at the Doheny Eye Institute. METHODS: The clinical and imaging
      records of a consecutive series of 71 eyes of 40 patients referred for DME who
      underwent OCT using the both the Macular Grid 5 (MG5) scanning protocol (to allow
      a more evenly distributed sampling of points in the macula) and the standard Fast
      Macular Thickness Map (FMTM) pattern were reviewed. An automated algorithm was
      developed to generate a retinal thickness map using the MG5 data, which was then
      compared with a normative database to identify presumed areas of retinal edema.
      Clinically significant macular edema (CSME) was also identified by clinical
      examination and stereoscopic fundus photographs for comparison with the results
      of the OCT protocols. MAIN OUTCOME MEASURES: Sensitivity and specificity of
      scanning protocols. RESULTS: Optical coherence tomograms were inspected visually,
      and automatically detected retinal boundaries were found to be correct in 69 of
      71 MG5 scans and in 65 of 71 FMTM scans. Macular Grid 5 scanning was performed
      twice in each eye, and the repeatability (pooled standard deviation) of the total
      area of edema was 0.48 mm2 (coefficient of variation, 6.8%). Sensitivity and
      specificity of the MG5 for detection of CSME relative to the clinical examination
      were 89% and 86%, respectively, with kappa being 0.74. Macular Grid 5 and FMTM
      assessment of foveal CSME also showed good agreement, with kappa being 0.68.
      CONCLUSIONS: The analysis algorithm for the OCT MG5 grid scan seems to be
      accurate and repeatable. Automated detection of CSME by the MG5 analysis
      correlated well with the clinical grading and standard OCT analysis (FMTM).
      Macular Grid 5 provides more information regarding the perifoveal macula than
      FMTM and may be of value to clinicians in planning treatment and in future
      studies of macular edema.

PMID- 16647124
TI  - Long-standing bullous keratopathy is associated with peripheral
      conjunctivalization and limbal deficiency.
AB  - OBJECTIVE: To investigate whether peripheral corneal neovascularization in
      bullous keratopathy (BK) is due to conjunctivalization, a sign of limbal stem
      cell deficiency. DESIGN: Observational case-control study. PARTICIPANTS: Sixteen
      BK patients. METHODS: Patients were divided into 2 groups: BK without peripheral
      neovascularization [NV(-) group; 5 patients, 5 eyes] and BK with
      neovascularization [NV(+) group; 11 patients, 13 eyes]. Evidence of
      conjunctivalization was evaluated by periodic acid-Schiff staining of impression
      cytology samples from the peripheral vascularized cornea. The 2 groups' durations
      of disease also were compared. Penetrating keratoplasty (PK) was performed in all
      16 cases, and the 2 groups' durations of reepithelialization after PK were
      compared. MAIN OUTCOME MEASURES: Presence of goblet cells using impression
      cytology, duration of BK, and duration of postoperative reepithelialization.
      RESULTS: Goblet cells were found on the peripheral corneal surface in all eyes in
      the NV(+) group. However, all eyes in the NV(-) group were negative for goblet
      cells (P<0.0001). Duration of disease was 14.4+/-5.4 months in the NV(-) group
      and 66.2+/-65.5 months in the NV(+) group (P = 0.030). Duration of postoperative
      epithelialization was 6.2+/-2.2 days in the NV(-) group and 28.8+/-36.5 days in
      the NV(+) group (P = 0.046). CONCLUSION: Conjunctivalization of the peripheral
      cornea and delayed postoperative epithelialization in BK patients with NV suggest
      the presence of limbal stem cell deficiency in such patients. Patients with long
      standing disease were found to be more prone to neovascularization. For this
      reason, early surgery may lead to a better surgical outcome.

PMID- 16647125
TI  - Incidence and types of childhood hypertropia: a population-based study.
AB  - OBJECTIVE: To determine the incidence and types of childhood hypertropia in a
      defined population. DESIGN: Retrospective population-based cohort. PARTICIPANTS:
      All pediatric (<19 years of age) residents of Olmsted County, Minnesota,
      diagnosed with vertical strabismus from January 1, 1985, through December 31,
      1994. METHODS: The medical records of all potential patients identified by the
      resources of the Rochester Epidemiology Project were reviewed. MAIN OUTCOME
      MEASURES: Incidence and types of childhood hypertropia. RESULTS: Forty-two cases
      of childhood hypertropia were identified during the 10-year period, yielding an
      annual age- and gender-adjusted incidence of 12.9 (95% confidence interval, 9.0
      16.9) per 100000 patients younger than 19 years of age. This rate corresponds to
      a prevalence of approximately 0.26%, or 1 in 391, of all children younger than 19
      years of age. Nearly three fourths (71.4%) of the children had a IVth cranial
      nerve palsy, primary inferior oblique overaction, Brown syndrome, or a vertical
      tropia in the setting of an abnormal central nervous system. CONCLUSIONS: The
      incidence rates for childhood hypertropia in this population-based study are
      higher than published reports of prevalence. Fourth cranial nerve palsy and
      primary dysfunction of the inferior oblique muscle were the most common forms of
      vertical strabismus in this population.

PMID- 16647126
TI  - Recalcitrant post-LASIK Mycobacterium chelonae keratitis eradicated after the use
      of fourth-generation fluoroquinolone.
AB  - OBJECTIVE: To report a patient with Mycobacterium chelonae keratitis after LASIK
      and discuss therapeutic measures. DESIGN: Interventional case report and
      literature review. INTERVENTION: A healthy, 25-year-old man presented 6 weeks
      after LASIK with infectious keratitis in the left eye. Scrapings were obtained
      from the central stromal bed after lifting the flap and inoculated on culture
      media. MAIN OUTCOME MEASURES: Response to medical treatment. RESULTS:
      Mycobacterium chelonae was identified from stromal bed scrapings. The protracted
      course of the infection necessitated surgical debridement and flap amputation
      with slow and suboptimal response to prolonged (14 weeks) treatment with topical
      amikacin 3.3%, clarithromycin 1%, and levofloxacin 0.5%. The substitution of
      levofloxacin 0.5% with gatifloxacin 0.3% resulted in closure of the epithelial
      defect within 1 week and resolution of the infiltrates in 3 weeks. The combined
      regimen of gatifloxacin 0.3%, amikacin 3.3%, and clarithromycin 1% was continued
      for a total of 4 months. The patient remains infection free 1 year after stopping
      all antibiotics. CONCLUSION: Treatment of post-LASIK nontuberculous mycobacteria
      remains a challenge. Institution of combination therapy including fortified
      amikacin, clarithromycin 1%, and a fourth-generation fluoroquinolone appeared to
      be beneficial in this patient.

PMID- 16647127
TI  - Optical coherence tomography analysis of the macula after vitrectomy surgery for
      retinal detachment.
AB  - OBJECTIVE: To define the incidence, duration, and clinical associations of
      persistent localized submacular fluid after pars plana vitrectomy (PPV) retinal
      detachment surgery. DESIGN: Observational cohort series. PARTICIPANTS: One
      hundred patients were identified and recruited into the study. METHODS: Patients
      aged 18 years and older who had undergone PPV and gas as a primary procedure for
      rhegmatogenous retinal detachment and postoperative follow-up were recruited from
      February through August 2004. All patients underwent clinical examination,
      optical coherence tomography (OCT) scan of the macula, and retinal thickness
      analysis scan of the macula. Those patients in whom an abnormality was seen on
      OCT at 6 weeks after surgery underwent follow-up with repeat of the study
      investigations at 3, 6, 9, 12, and 18 months after surgery until the abnormality
      resolved. If no abnormality was seen at the 6-week examination, no further
      investigation was undertaken. Demographic data, including detachment
      characteristics, were collected retrospectively from the patient case notes. MAIN
      OUTCOME MEASURES: The principle outcome measure was the presence of subretinal
      fluid (SRF) on OCT at 6 weeks after surgery. Other outcome measures included
      duration of persistent fluid and association with visual outcome and type and
      duration of detachment. RESULTS: One hundred patients were recruited; 15 of these
      had SRF on OCT performed at 6 weeks after surgery. Subretinal fluid was
      associated with significantly worse visual acuity (VA) at 6 weeks (P = 0.033,
      Wilcoxon rank-sum); those with SRF had a median VA of 0.4, and those with no SRF
      had a median VA of 0.3. The fluid took a median of 5.5 months to resolve. Seven
      patients had combined PPV and scleral buckle surgery; none of these had fluid at
      6 weeks. CONCLUSIONS: Optical coherence tomography is a useful noninvasive
      diagnostic method that can detect SRF not appreciated on clinical examination.
      Persistent SRF after PPV and gas surgery occurred in 15% of patients in this
      study and was still present in 53% of these at 6 months. The presence of SRF at 6
      weeks after surgery was associated with a poorer visual outcome at this time
      point.

PMID- 16647128
TI  - The course of intermittent exotropia in a population-based cohort.
AB  - PURPOSE: To evaluate the change in the angle of deviation in an incidence cohort
      of pediatric patients diagnosed with intermittent exotropia during a 20-year
      period. DESIGN: Retrospective, population-based observational study.
      PARTICIPANTS: All pediatric (<19 years old) residents of Olmsted County,
      Minnesota diagnosed with intermittent exotropia (> or =10 prism diopters) from
      January 1, 1975 through December 31, 1994. METHODS: The medical records of all
      potential patients identified by the resources of the Rochester Epidemiology
      Project were reviewed. MAIN OUTCOME MEASURES: The change in the angle of
      deviation and its association with treatment were reviewed for each patient.
      RESULTS: A total of 184 pediatric patients were diagnosed during the study
      period, of which 138 patients (75.0%) had > or =2 examinations. The deviation
      resolved in 5 of the 138 patients (3.6%) during a median follow-up of 9.2 years,
      while the Kaplan-Meier rate of increasing by 10 or more prism diopters (PD) was
      23.1% at 5 years and 52.8% at 20 years. The distance deviation increased by a
      median of 5 PD during the preoperative period in the 55 patients who underwent
      surgery during a mean follow-up of 3.2 years compared with a zero PD median
      change in the 83 patients who avoided surgery during a mean follow-up of 7.1
      years. The Kaplan-Meier probability of undergoing surgery within 20 years after
      diagnosis was 74.0% in this population. We were unable to detect a significant
      association between nonsurgical treatments and a change in the angle of
      deviation. CONCLUSIONS: In this population-based cohort of pediatric patients
      with intermittent exotropia, the deviation resolved in 4%, and more than half of
      the patients were expected to have an increase of 10 or more PD within 20 years
      of their diagnosis. Children who received surgery in this population were
      significantly more likely to have demonstrated an increase in their deviation
      during the preoperative period.

PMID- 16647129
TI  - Oral chlorambucil for extranodal, marginal zone, B-cell lymphoma of mucosa
      associated lymphoid tissue of the orbit.
AB  - PURPOSE: To report the outcome of oral chlorambucil as a single treatment in
      patients with orbital mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN:
      Retrospective nonrandomized clinical study. PARTICIPANTS: Thirty-three patients
      with isolated orbital MALT lymphoma. METHODS: Medical records of all patients
      with histology-verified orbital MALT lymphoma treated with oral chlorambucil at
      the Royal Melbourne Hospital were reviewed. MAIN OUTCOME MEASURES: Complete
      clinical response, partial response, local relapse, systemic extension (distant
      relapse), and survival. RESULTS: Thirty-three patients (19 female; mean age, 69
      years) participated in the study. Patients received an average of 4 courses of
      oral chlorambucil with a mean total dose of 600 mg. The lacrimal gland was the
      most frequent site of occurrence (24%), followed by the conjunctiva, eyelid, and
      superior orbit. Orbital mass, swelling, and diplopia were common presenting
      signs. Complete response was noted in 26 patients (79%). In 2 of the patients
      with complete clinical response, mild residual thickening was noted on follow-up
      orbital imaging studies. Four patients (12%) showed disease recurrence or
      relapse. Mean follow-up time was 32 (+/-20) months (range, 8 months-6 years;
      median, 26 months). None of the patients developed granulocytopenia secondary to
      chemotherapy, and none suffered significant nausea or vomiting. One patient with
      malignant transformation died 12 months after diagnosis and initial treatment.
      CONCLUSIONS: Systemic chemotherapy with chlorambucil is a reasonable option in
      patients with orbital MALT lymphoma. It is associated with minimal to no side
      effects. Additionally, it may be well tolerated by elderly patients and also may
      treat subclinical disease elsewhere.

PMID- 16647130
TI  - LASIK outcomes in patients with underlying systemic contraindications: a
      preliminary study.
AB  - OBJECTIVES: To determine the anatomic and functional outcomes of photorefractive
      surgery in patients with underlying systemic diseases that are traditionally
      listed as relative or absolute contraindications. DESIGN: Observational
      retrospective case-control study. PARTICIPANTS: The case groups were composed of
      275 eyes of 141 consecutive patients who underwent a LASIK procedure with any of
      the following underlying conditions: autoimmune connective-tissue disorders (n =
      62), psoriasis (n = 91), intestinal inflammatory diseases (n = 67), diabetes
      mellitus (n = 44), and history of keloid formation (n = 18). Twenty-nine patients
      (56 eyes) were receiving systemic immunosuppressive therapy. The control group
      comprised 358 eyes of 181 patients without the above-mentioned conditions who
      underwent LASIK. METHODS: The study had 2 parts, relating to the anatomic and
      functional (visual and refractive) outcomes. For anatomic outcome, we compared
      the entire sample of both groups. For functional outcome, only myopic eyes of
      each group were compared. Independent comparisons were performed between each
      disease group and the control group. MAIN OUTCOME MEASURES: Anatomic outcomes
      included perioperative and postoperative epithelial, flap, and interface
      complications. Functional outcomes were evaluated using visual and refractive
      indicators, percentage of eyes undergoing enhancement, and number of
      postoperative visits. RESULTS: Mild anatomic complications were observed in the
      case and control groups with similar percentages, and there were no statistical
      differences between groups. Regarding functional outcome, the only significant
      finding was a worse refractive outcome in the collagen vascular diseases group
      compared with controls. There were no other statistical differences detected in
      the other systemic disease groups. CONCLUSIONS: In our experience, LASIK can be
      performed effectively and safely in selected patients with stable and controlled
      systemic diseases with favorable postoperative anatomic and visual outcomes. The
      absolute exclusion of certain systemic contraindications should be reconsidered.

PMID- 16647131
TI  - Three-year follow-up analysis of Artisan toric lens implantation for correction
      of postkeratoplasty ametropia in phakic and pseudophakic eyes.
AB  - PURPOSE: To determine the 3-year follow-up of efficacy and safety of Artisan
      toric iris-fixated lens implantation after penetrating keratoplasty (PK) to
      correct high ametropia and astigmatism. DESIGN: Prospective noncomparative case
      series with a minimum follow-up of 1 year. PARTICIPANTS: Artisan toric lens
      implantation was performed in 36 eyes of 35 patients who were contact lens
      intolerant or unable to wear glasses due to anisometropia and/or high
      astigmatism. INTERVENTION: Thirty-six eyes of 35 consecutive patients received
      Artisan toric lens implantation for postkeratoplasty astigmatism and/or
      anisometropia. MAIN OUTCOME MEASURES: Manifest refraction, uncorrected visual
      acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and corneal
      topography were determined or performed before surgery and at 3, 6, and 12 months
      and yearly intervals up to 4 years after surgery. Efficacy, safety, percent
      reduction of refractive astigmatism, anisometropia of defocus, and the
      astigmatism correction index were determined. A patient satisfaction
      questionnaire and specular microscopy were assessed. RESULTS: The mean +/-
      standard deviation of preoperative refractive cylinder was -7.06+/-2.01 diopters
      (D) (range, -3.0 to -11.0), which was reduced to -1.73+/-1.25 D, -1.69+/-1.15 D, 
      1.94+/-1.68 D, -2.02+/-1.93 D, and -2.00+/-1.53 D at 6 months (n = 36), 1 year (n
      = 36), 2 years (n = 29), 3 years (n = 15), and the last follow-up examination
      (28.5+/-12.5 months, n = 36), respectively (P<0.001 for all time points, paired t
      test). The spherical equivalent was reduced from -3.19+/-4.31 D (range, +5.5 to 
      14.25 D) preoperatively to -1.03+/-1.20 D (range, +1.0 to -5.25 D) at the last
      follow-up. The UCVA and BSCVA were > or =20/40 in 31.6% and 80.6%, respectively.
      There was a loss of BSCVA of >2 lines in 8.3% of eyes and a gain of at least 2
      lines in 8.3% of eyes. Percent reductions in refractive astigmatism and
      anisometropia of defocus were 88.8%+/-29.5% and 77.8%+/-19.3%, respectively. The
      astigmatism correction index was 96.0%+/-24.2%. Satisfaction increased from 3.6
      to 8.0 (scale, 0-10) after implantation. The endothelial cell loss as compared
      with preoperatively was 13.8%+/-18.7% (n = 34), 21.2%+/-21.8% (n = 33), 29.6%+/
      27.3% (n = 26), 30.4%+/-32.0% (n = 18), and 34.8%+/-26.3% (n = 6) at 6 months (P
      = 0.001), 1 year (P<0.001), 2 years (P<0.001), 3 years (P = 0.001), and 4 years
      postoperatively (P = 0.1), respectively. In 2 patients, irreversible graft
      rejections occurred, and in 1 patient, gradual endothelial decompensation
      occurred. CONCLUSION: Artisan toric lens implantation after PK was effective for
      reduction of refractive astigmatism and ametropia. All patients were suitable for
      spectacle correction after implantation. There was continuing endothelial cell
      loss from 6 months to 3 years postoperatively. In 3 cases, corneal graft failure
      developed.

PMID- 16647132
TI  - Intereye concordance in locations of visual field defects in primary open-angle
      glaucoma: diagnostic innovations in glaucoma study.
AB  - PURPOSE: To determine the overlap in defective visual field locations between the
      right and left eyes of primary open-angle glaucoma patients. DESIGN: Cross
      sectional retrospective analysis of data from a prospectively designed
      longitudinal study. PARTICIPANTS: Patients with glaucomatous optic neuropathy in
      at least 1 eye and 2 consecutive reliable standard automated perimetry fields
      within 15 months were included, yielding 468 eyes of 234 patients. METHODS:
      Concordance in defective visual field locations between right and left eyes were
      calculated as the number of overlapping locations divided by the total number of
      defective locations (intereye concordance ratio). Concordance ratios also were
      calculated within an eye over time (intraeye concordance ratio) and between
      unmatched pairs of fields (unmatched concordance ratio). RESULTS: Intereye
      concordance (0.24+/-0.02) was significantly smaller than intraeye concordance
      (0.37+/-0.02) and significantly larger than unmatched concordance (0.14+/-0.01).
      There was a significant interaction between concordance type and defect size,
      such that there was no difference in concordance ratios for defects of fewer than
      8 locations, and the difference between intereye concordance versus intraeye
      concordance and unmatched concordance ratios increased with larger defect sizes.
      CONCLUSIONS: A spatial relationship exists between defective locations of an
      individual's eyes. Future studies will show whether information about the spatial
      relationship is useful to guide the modification of visual field test locations
      to improve detection of loss and perhaps also progression.

PMID- 16647133
TI  - Causes of blindness and visual impairment in urban and rural areas in Beijing:
      the Beijing Eye Study.
AB  - OBJECTIVE: To evaluate the causes of visual impairment and blindness in adult
      Chinese in an urban and rural region of Beijing, China. DESIGN: Population-based
      prevalence survey. PARTICIPANTS: From a rural region and an urban region of
      Greater Beijing, 4439 of 5324 > or=40-year-old invited subjects participated in
      the study (response rate, 83.4%). Using the World Health Organization (WHO)
      standard and the United States standard, blindness was defined as best-corrected
      visual acuity (BCVA) in the better-seeing eye of <20/400 and of <2/20,
      respectively, and visual impairment was defined as best-corrected vision of
      <20/60 and > or =20/400, and of <20/40 and > or =2/20, respectively. METHODS:
      Determination of BCVA, pneumotonometry, frequency doubling perimetry, evaluation
      of photographs of the fundus and lens, and clinical examination. MAIN OUTCOME
      MEASURE: Causes of visual impairment and blindness. RESULTS: Visual acuity
      measurements were available for 8816 eyes of 4409 subjects (99.3%). Using the WHO
      standard and the U.S. standard, 49 (1.1%) subjects and 95 (2.2%) subjects,
      respectively, had low vision, and 13 (0.3%) subjects and 15 (0.3%) subjects,
      respectively, were blind by definition. Taking the whole study population, the
      most frequent cause of low vision/blindness was cataract (36.7%/38.5%), followed
      by degenerative myopia (32.7%/7.7%), glaucoma (14.3%/7.7%), corneal opacity
      (6.1%/15.4%), and other optic nerve damage (2.0%/7.7%). Age-related macular
      degeneration (AMD) (2.0%/7.7%) and diabetic retinopathy (0%/7.7%) were
      responsible for a minority of cases. In subjects 40 to 49 years old, the most
      frequent cause of low vision and blindness was degenerative myopia. In the 50- to
      59-year age group, the most frequent cause was cataract, followed by degenerative
      myopia. In the 60- to 69-year-old subjects and the > or =70-year group, the most
      frequent cause of low vision and blindness was cataract, followed by degenerative
      myopia and glaucoma. CONCLUSIONS: The most frequent cause of low vision and
      blindness in adult Chinese is cataract, followed by degenerative myopia and
      glaucomatous optic neuropathy, with degenerative myopia dominating in younger
      groups and cataract dominating in elder groups. In contrast to studies in Western
      countries, AMD and diabetic retinopathy appear to play a minor role as a cause of
      visual impairment in elderly Chinese.

PMID- 16647134
TI  - Pegaptanib sodium for neovascular age-related macular degeneration: two-year
      safety results of the two prospective, multicenter, controlled clinical trials.
AB  - OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific
      vascular endothelial growth factor (VEGF) antagonist, in the treatment of
      neovascular age-related macular degeneration (AMD) during 2 years of therapy.
      DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham
      controlled studies. METHODS: Patients with all angiographic choroidal
      neovascularization lesion compositions of AMD received either intravitreous
      pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54
      weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to
      continue or discontinue therapy for 48 more weeks; sham-treated patients were re
      randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the
      pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious
      adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at
      least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n
      = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2,
      425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51)
      continued the same masked treatment as in year 1 and received at least one study
      treatment in year 2; 2663 intravitreous injections of pegaptanib were
      administered in these subjects. RESULTS: All doses of pegaptanib were well
      tolerated. The most common ocular adverse events were transient, mild to moderate
      in intensity, and attributed to the injection preparation and procedure. There
      was no evidence of an increase in deaths, in events associated with systemic VEGF
      inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic
      events), or in severe ocular inflammation, cataract progression, or glaucoma in
      pegaptanib-treated patients relative to sham-treated patients. In year 1, serious
      injection-related complications included endophthalmitis (12 events,
      0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2
      exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection).
      Most cases of endophthalmitis followed violations of the injection preparation
      protocol. In patients receiving pegaptanib for >1 year, there were no reports of
      endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients
      (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of
      pegaptanib sodium is favorable in patients with exudative AMD.

PMID- 16647135
TI  - Trabeculectomy with mitomycin C: outcomes and risk factors for failure in phakic
      open-angle glaucoma.
AB  - PURPOSE: To evaluate long-term tonometric outcomes of trabeculectomy with
      adjunctive mitomycin C (MMC) and its efficacy in achieving a range of intraocular
      pressures (IOP) in phakic patients with open-angle glaucoma. DESIGN:
      Retrospective cohort study. METHODS: Three levels of success were defined by
      these criteria: (A) IOP < or =18 mmHg and IOP reduction of 20%; (B) IOP < or =15
      mmHg and IOP reduction of 25%; and (C) IOP < or =12 and IOP reduction of 30%.
      Kaplan-Meier survival analyses were used to assess outcomes. Cox's proportional
      hazard regression analysis was used to identify risk factors for failure.
      PARTICIPANTS: Two hundred twenty-five phakic patients (292 eyes) with open-angle
      glaucoma, > or =40 years of age at time of trabeculectomy. MAIN OUTCOME MEASURES:
      The primary outcome was qualified success rate (with or without medications)
      according to the defined criteria. Secondary outcomes include IOP level and
      number of medications at 1 and 3 years after surgery, postoperative
      complications, and need for further glaucoma surgery. RESULTS: Mean IOP (+/
      standard deviation) decreased from 18.8 mmHg (+/-6.1 mmHg) before surgery to 11.3
      mmHg (+/-4.5 mmHg) at 1 year and 11.1 mmHg (+/-4.2 mmHg) at 3 years (P<0.001 for
      both). The mean number of medications decreased from 2.8 (+/-1.0) to 0.4 (+/-0.7)
      at 1 year and 0.7 (+/-1.0) at 3 years (P<0.001 for both). The success rates were
      85%, 84%, and 79% at 1 year for criteria A, B, and C, respectively; and 62%, 56%,
      and 46% for these criteria, respectively, at 3 years. Postoperative laser suture
      lysis was associated with a higher rate of failure for criteria B and C (P<0.001
      for both), the hazard ratio (HR) was 1.7 for criteria B and 2.0 for criteria C.
      Prior argon laser trabeculoplasty was associated with higher risk of failure for
      criteria C (HR = 1.6; P = 0.05). CONCLUSIONS: Trabeculectomy with MMC effectively
      reduces IOP in phakic open-angle glaucoma, but long-term low IOPs are achieved in
      only half of the cases. Laser suture lysis after trabeculectomy and prior argon
      laser trabeculoplasty are associated with a higher risk of failure when low IOPs
      are required.

PMID- 16647136
TI  - High signal intensity on magnetic resonance imaging as a predictor of
      neurobehavioral performance of workers exposed to manganese.
AB  - INTRODUCTION: Using previously obtained cross-sectional data from a nationwide
      survey on workers exposed to manganese (Mn), we assessed the relation of high
      signal intensity with neurobehavioral effects, and reevaluated the preexisting
      cross-sectional data to get additional findings on the relation of high signals
      with other Mn-exposure indices. SUBJECTS AND METHODS: Subjects were the same as
      those in the previous study. The exposure status was reassessed based on similar
      exposure groups. The signal intensity of the globus pallidus (GP) relative to
      frontal white matter was subjectively evaluated as either with or without
      increased signals, and the increased signals were further graded into three
      categories. For quantitative evaluation of signal intensities of the GP we also
      calculated the pallidal index (PI). Neurobehavioral function was assessed using
      the World Health Organization Neurobehavioral Core Test Battery. In addition,
      computerized finger tapping speed was included to assess motor speed. RESULTS:
      The mean blood Mn for those with grade III was significantly greater than those
      without increased signals and those with grade I. Airborne Mn and PI also showed
      similar findings. PI paralleled subjective MRI gradings. The proportion of
      workers with increased signals increased with all the Mn-exposure variables,
      airborne and blood Mn, the duration of work, and cumulative exposure. The PI was
      significantly associated with a correct score of pursuit aiming II tests and
      finger tapping of the dominant hand after control of age and educational level
      among neurobehavioral performances. DISCUSSION: The present findings showed that
      signal index on T1-weighted MRI showed a dose-response relationship with all the
      Mn-exposure variables. The two neurobehavioral tests reflecting fine motor
      function were significantly decreased above 107.1 of PI, the cutoff point between
      those with and without increased signals. Hence, signal intensity on MRI is an
      effective predictor of the neurobehavioral performance of Mn exposed workers.

PMID- 16647137
TI  - Relaxin-a pleiotropic hormone and its emerging role for experimental and clinical
      therapeutics.
AB  - The insulin-related peptide hormone relaxin (Rlx) is known as pregnancy hormone
      for decades. In the 1980s, researchers began to recognize the highly intriguing
      fact that Rlx plays a role in a multitude of physiological processes far beyond
      pregnancy and reproduction. So, Rlx's contribution to the regulation of
      vasotonus, plasma osmolality, angiogenesis, collagen turnover, and renal function
      has been established. In addition, the peptide has been demonstrated to represent
      a mediator of cardiovascular pathology. The ongoing efforts to identify Rlx
      receptors eventually precipitated the discovery of the G protein-coupled
      receptors (GPCR) LGR7 and LGR8 as membrane receptors for human Rlx-2 in 2002.
      This review will summarize the current state of insight into this rapidly
      evolving field, which has further been expanded by the discovery of GPCR135 and
      GPCR142 as receptors for Rlx-3. In addition, Rlx has also been shown to activate
      the human glucocorticoid receptor (GR). There is evidence from Rlx and Rlx
      receptor knockouts suggesting that LGR7 is the only relevant receptor for mouse
      Rlx-1 (corresponding to human Rlx-2) in vivo and that insulin-like peptide (INSL)
      3 represents the physiological ligand for LGR8. Regarding Rlx signal
      transduction, the cyclic adenosine monophosphate (cAMP) and nitric oxide (NO)
      pathways will be characterized as major cascades. Investigation of downstream
      signaling remains an important field for future research. Finally, the current
      state of therapeutical strategies using Rlx in animal models as well as in humans
      is summarized.

PMID- 16647138
TI  - Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and
      involvement in neurological disorders.
AB  - Three enzyme systems, cyclooxygenases that generate prostaglandins, lipoxygenases
      that form hydroxy derivatives and leukotrienes, and epoxygenases that give rise
      to epoxyeicosatrienoic products, metabolize arachidonic acid after its release
      from neural membrane phospholipids by the action of phospholipase A(2).
      Lysophospholipids, the other products of phospholipase A(2) reactions, are either
      reacylated or metabolized to platelet-activating factor. Under normal conditions,
      these metabolites play important roles in synaptic function, cerebral blood flow
      regulation, apoptosis, angiogenesis, and gene expression. Increased activities of
      cyclooxygenases, lipoxygenases, and epoxygenases under pathological situations
      such as ischemia, epilepsy, Alzheimer's disease, Parkinson disease, amyotrophic
      lateral sclerosis, and Creutzfeldt-Jakob disease produce neuroinflammation
      involving vasodilation and vasoconstriction, platelet aggregation, leukocyte
      chemotaxis and release of cytokines, and oxidative stress. These are closely
      associated with the neural cell injury which occurs in these neurological
      conditions. The metabolic products of docosahexaenoic acid, through these
      enzymes, generate a new class of lipid mediators, namely docosatrienes and
      resolvins. These metabolites antagonize the effect of metabolites derived from
      arachidonic acid. Recent studies provide insight into how these arachidonic acid
      metabolites interact with each other and other bioactive mediators such as
      platelet-activating factor, endocannabinoids, and docosatrienes under normal and
      pathological conditions. Here, we review present knowledge of the functions of
      cyclooxygenases, lipoxygenases, and epoxygenases in brain and their association
      with neurodegenerative diseases.

PMID- 16647139
TI  - Personality and seasonal affective disorder: results from the CAN-SAD study.
AB  - BACKGROUND: Personality factors have been implicated in seasonal affective
      disorder (SAD). The present study investigated the relationship between the five
      factor model of personality (neuroticism, extraversion, openness, agreeableness,
      conscientiousness) and SAD. METHODS: Ninety-five patients with SAD completed
      personality measures before and after treatment in a clinical trial and during
      the summer months. The personality scores of the SAD patients were compared with
      a matched group of non-seasonal depressed patients and published normative data.
      Stability and change in personality scores with changes in mood state were
      assessed. Personality dimensions were evaluated as possible predictors of
      treatment outcome. RESULTS: SAD patients showed elevated openness scores relative
      to both non-seasonal depressed patients and norms. Their neuroticism scores were
      lower than non-seasonal depressed patients, but higher than norms. All
      personality dimensions showed large and highly significant test-retest
      correlations but several personality dimensions, particularly neuroticism and
      extraversion, also showed considerable change with changing mood state. None of
      the personality dimensions were significantly associated with treatment outcome.
      LIMITATIONS: Personality assessment relied on self-report. CONCLUSIONS: The
      personality profile of SAD patients differs from both non-seasonal depressed
      patients and norms. Elevated openness scores appear to be a unique feature of
      patients with SAD. Since mood state has a significant impact on personality
      scores, assessment of personality in SAD patients should ideally be conducted
      when they are in remission. Further investigation of the relationship between
      personality and SAD, especially the potential significance of elevated openness
      scores, is warranted.

PMID- 16647140
TI  - The role of negative interpretations of intrusive memories in depression.
AB  - BACKGROUND: Recent investigations have shown that intrusive memories of negative
      past events, the hallmark symptom of posttraumatic stress disorder (PTSD), are
      also commonly experienced in depression. This study explored whether Ehlers and
      Steil's [Ehlers, A., Steil, R., 1995. Maintenance of intrusive memories in
      posttraumatic stress disorder: a cognitive approach. Behavioural and Cognitive
      Psychotherapy, 23, 217-249] model of PTSD maintenance, which focuses on the role
      played by negative interpretations of intrusive symptoms in the persistence of
      PTSD, also describes processes that operate in depression. METHODS: Eighty-four
      undergraduate students were interviewed to identify the presence of intrusive
      memories in the previous week. Participants who reported an intrusive memory were
      administered self-report questionnaires that indexed cognitive and affective
      responses to the memory. RESULTS: Negative interpretations of intrusive memories
      were significantly correlated with cognitive avoidance (particularly rumination)
      and depression severity, after controlling for intrusion frequency and severity
      of memory content. Negative meaning was the strongest predictor of depression,
      explaining variance over and above intrusion frequency. Ruminative responses to
      intrusions were highly correlated with depression. LIMITATIONS: The use of an
      unselected student sample. CONCLUSIONS: The demonstrated utility of Ehlers and
      Steil's [Ehlers, A., Steil, R., 1995. Maintenance of intrusive memories in
      posttraumatic stress disorder: A cognitive approach. Behavioural and Cognitive
      Psychotherapy, 23, 217-249] model of PTSD to account for one aspect of depression
      maintenance supports recent commentaries [Harvey, A.G., Watkins, E., Mansell, W.,
      Shafran, R., 2004. Cognitive behavioural processes across psychological
      disorders: A transdiagnostic approach to research and treatment. New York: Oxford
      University Press] that call for a transdiagnostic approach to understanding the
      cognitive and behavioural processes that underpin psychological disorders.

PMID- 16647141
TI  - Deficient inhibition of emotional information in depression.
AB  - BACKGROUND: There are numerous indications that impaired inhibition of negative
      affective material could be an important cognitive component of depression. To
      study whether impaired inhibition of negative affect is a cognitive vulnerability
      factor explaining (recurrent) depression, inhibition of positive and negative
      affective stimuli was examined in hospitalized depressed patients, formerly
      depressed individuals and never-depressed controls. METHODS: To investigate
      inhibitory dysfunctions in the processing of emotional material, we used an
      affective modification of the negative priming task with pictures of sad and
      happy facial expressions. RESULTS: Compared to never-depressed controls,
      depressed patients showed a specific failure to inhibit negative information,
      whereas inhibition function for positive material was unaffected. Surprisingly,
      formerly depressed individuals demonstrated impaired inhibition of negative and
      positive information. LIMITATIONS: Because of the significant correlations
      between depression and anxiety self-report scores, the observed reduced
      inhibitory effect toward negative material in the depression group cannot
      strictly be attributed as depression-specific. CONCLUSIONS: In accordance with
      our hypothesis, strongly impaired inhibition of negative affect was found in
      depressed patients. Based on the present findings, we argue that impaired
      inhibition of negative affect could be an important construct in cognitive
      theories on depression linking cognitive biases to neuropsychological impairments
      in depression. The data in the formerly depressed individuals are less conclusive
      and several hypotheses are detailed that could explain how the absence of
      inhibition of affective information could relate to recurrent depression.

PMID- 16647142
TI  - Platelet serotonin in combat related posttraumatic stress disorder with psychotic
      symptoms.
AB  - BACKGROUND: Combat-related posttraumatic stress disorder (PTSD) is severe form of
      PTSD, frequently associated with psychotic symptoms. Platelet serotonin (5
      hydroxytryptamine, 5-HT) was used as a peripheral 5-HT marker to identify
      particular symptoms in PTSD. METHODS: Platelet 5-HT was determined
      fluorimetrically in 67 war veterans with combat related PTSD, 36 combat exposed
      veterans who did not develop PTSD, 35 veterans with PTSD complicated with
      psychotic features. PTSD diagnosis of current and chronic PTSD, and clinical
      symptoms of PTSD and psychoses were assessed according to DSM-IV criteria, using
      the Clinician Administrated PTSD Scale, and Positive and Negative Syndrome Scale
      (PANSS). RESULTS: Platelet 5-HT concentration was significantly higher in
      veterans with psychotic PTSD than in veterans with non-psychotic PTSD, veterans
      without PTSD, or in control subjects. Platelet 5-HT was significantly positively
      correlated with the positive symptoms in PANSS subscale, and with the symptoms of
      delusions within PANSS positive subscale. LIMITATIONS: The results were obtained
      on peripheral 5-HT marker, i.e. platelet 5-HT concentration. CONCLUSIONS: Since
      the delusions are the core psychotic symptoms occurring in our psychotic PTSD
      patients, the result of the increased platelet 5-HT concentration, associated
      with delusions, indicate that platelet 5-HT might be used as a trait marker of
      psychotic symptoms in PTSD, but not as a state marker for PTSD.

PMID- 16647143
TI  - Enhanced antitumor effect of dendritic cell based immunotherapy after
      intratumoral injection of radionuclide Ho-166 against B16 melanoma.
AB  - Internal radiotherapy with the intratumoral injection of the beta-emitting
      radionuclide, Holmium (Ho)-166, into B16 melanoma resulted in a reduction in size
      and growth rate; however, complete remission was not always achieved. Therefore,
      additional dendritic cell (DC) therapy was investigated to determine whether it
      could improve therapeutic results. Malignant melanoma was induced in mice by
      inoculating B16F10 cell line subcutaneously. Fifty-four mice were divided into
      four groups: (1) non-treated (group I, n = 11), (2) treated with Ho-166 (group
      II, n = 16), (3) treated with immature DCs (group III, n = 8), and (4) treated
      with immature DCs after Ho-166 injection (group IV, n = 19). Changes in tumor
      size, survival rates, and immunologic profiles were observed. Nineteen days after
      Ho-166 or PBS injection, mean tumor sizes in the four groups were 6044 +/- 1046,
      1658 +/- 523, 3871 +/- 921, and 444 +/- 167 mm(3), respectively. We observed a
      significant decrease in tumor size (P < 0.05) and an increase in survival in
      group IV. When the B16F10 cell line was reinjected into the contralateral backs
      of survivors, much slower growth was observed in group IV (P < 0.05). Both tumor
      specific CTL and natural killer cell activities and the infiltration of
      inflammatory cells into tumor tissues were found to be elevated in group IV. In
      addition, strong immune responses as determined by in vitro T cell proliferation,
      ELISA and ELISPOT assay were induced in group IV. Our results suggest that a
      combination of internal radiotherapy using Ho-166 and immature DCs could be used
      either to treat unresectable melanoma or as an adjuvant therapy after surgery.

PMID- 16647144
TI  - Immunomodulation of TGF-beta 1 in mdx mouse inhibits connective tissue
      proliferation in diaphragm but increases inflammatory response: implications for
      antifibrotic therapy.
AB  - Irreversible connective tissue proliferation in muscle is a pathological hallmark
      of Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease due
      to lack of the sarcolemmal protein dystrophin. Focal release of transforming
      growth factor-beta1 (TGF-beta1) is involved in fibrosis development. Murine
      muscular dystrophy (mdx) is genetically homologous to DMD and histopathological
      alterations comparable to those in DMD muscles occur in diaphragm of older mdx
      mice. To investigate the early development of fibrosis and TGF-beta1 involvement,
      we assessed diaphragms in 6-36-week-old mdx and C57/BL6 (control) mice for
      fibrosis, and used real-time PCR and ELISA to determine TGF-beta1 expression.
      Significantly greater fibrosis and TGF-beta1 expression were found in mdx from
      the 6th week. Mice treated with neutralizing antibody against TGF-beta1 had lower
      levels of TGF-beta1 protein, reduced fibrosis, unchanged muscles fiber
      degeneration/regeneration, but increased inflammatory cells (CD4+lymphocytes).
      These data demonstrate early and progressive fibrosis in mdx diaphragm
      accompanied by TGF-beta1 upregulation. Reduction of TGF-beta1 appears promising
      as a therapeutic approach to muscle fibrosis, but further studies are required to
      evaluate long term effects of TGF-beta1 immunomodulation on the immune system.

PMID- 16647145
TI  - Construction and characterization of bacterial artificial chromosomes containing
      HSV-1 strains 17 and KOS.
AB  - Bacterial artificial chromosomes (BACs) were constructed containing full-length,
      infectious DNA of HSV-1 strains 17 and KOS. To generate BACs without altering
      viral genes, sequences required for selection and propagation of the BAC were
      placed between the U(L)37 and U(L)38 genes, and flanked by LoxP sites. The system
      was tested by studying multiple properties of these HSV-1 BAC constructs in vitro
      and in vivo following propagation in bacteria, virus reconstitution from HSV-BAC
      DNA in eukaryotic cells, and Cre-recombinase-mediated excision of the BAC
      backbone. Based on in vitro growth in mouse embryo fibroblasts and in vivo growth
      in mouse corneas and trigeminal ganglia, the strain KOS BAC-derived virus behaved
      similarly to wild-type. Small changes in neurovirulence were, however, observed.
      The strain 17 BAC-derived virus exhibited modest decreases in growth and
      virulence compared to wild-type. Modest differences were observed in reactivation
      from latency with both strain KOS and 17 BAC-derived viruses. In addition, the
      system was further validated by performing mutagenesis of the BACs by allelic
      exchange in E. coli. These BACs are suitable for the rapid generation of
      recombinant viruses for pathogenesis and other studies, but as with all
      mutagenesis systems, care must be taken in their construction and repair.

PMID- 16647146
TI  - Acute toxicity profile of cadmium revealed by proteomics in brain tissue of
      Paralichthys olivaceus: potential role of transferrin in cadmium toxicity.
AB  - An analytical approach using two-dimensional polyacrylamide gel electrophoresis
      (2D-PAGE) separated proteins from the brain tissue of the fish Paralichthys
      olivaceus. Approximately 600 protein spots were detected from the brain sample
      when applying 600 microg protein to a 2D-PAGE gel in the pH range 3.5-10.0.
      Compared to a control sample, significant changes of 24 protein spots were
      observed in the fish tissue exposed to acute toxicity of seawater cadmium (SCAT)
      at 10 ppm for 24h. Among these spots, nine were down-regulated, nine were up
      regulated, two showed high expression, and four showed low expression. The
      collected spots were identified by peptide mass fingerprinting (PMF) and database
      search, and they were further classified by LOC tree, a hierarchical system of
      support vector machines which predict their sub-cellular localization. The amount
      of transferrin expression in brain cells decreased linearly with the increase of
      SCAT concentration in seawater. Among the 24 proteins identified on a 2D-PAGE
      gel, 9 demonstrated a synchronous response to acute cadmium, suggesting that they
      might represent a biomarker profile. Based on their variable levels and trends on
      the 2D-PAGE gel this protein (likely to be transferrin) suggesting they might be
      utilized as biomarkers to investigate cadmium pollution levels in seawater and
      halobios survival, as well as to evaluate the degree of risk of human fatalities.
      The results indicate that the application of multiple biomarkers has an advantage
      over a single biomarker for monitoring levels of environmental contamination.

PMID- 16647147
TI  - Role of C-C chemokines in Takayasu's arteritis disease.
AB  - BACKGROUND: Takayasu's arteritis (TA) is a chronic obliterative inflammatory
      disease. Inflammatory cell infiltration and destruction of the vessel wall in TA
      strongly suggest that cell mediated immunological mechanisms play an important
      role in the pathogenesis of this disease. Therefore, in the present study our aim
      was to focus on the role of chemokines and adhesion molecules in patients with
      Takayasu's disease. METHODS: Twenty-one patients with clinically defined TA and
      21 healthy control volunteers were recruited by using the standard criteria.
      Patients with TA were divided into those with clear-cut clinically active or
      inactive disease based on vasculitis activity score. RESULTS: MCP-1 and hRANTES
      were significantly increased in patients with TA as compared to controls. MCP-1
      and hRANTES values were reliably able to distinguish between patients with active
      disease vs. subjects in remission. sVCAM-1 levels remained unaltered between
      patients and controls. CONCLUSIONS: C-C chemokines can be used as reliable
      markers/diagnostic tools in determining the activity of Takayasu's arteritis.

PMID- 16647148
TI  - Clostridium difficile and Clostridium perfringens species detected in infant
      faecal microbiota using 16S rRNA targeted probes.
AB  - Clostridium perfringens and Clostridium difficile are pathogenic clostridia
      potentially associated with gastrointestinal infections and allergy in infants.
      To enable the molecular detection and quantification of these species in the
      infant gut, two 16S rRNA oligonucleotide probes were developed: Cdif198 for C.
      difficile and Cperf191 for C. perfringens. We defined the probes in silico using
      the RDP sequence database. The probes were then validated using FISH combined
      with flow cytometry and a collection of target and non-target strains, and faecal
      samples inoculated with dilutions of C. difficile and C. perfringens strains.
      These new probes were used to assess the composition of the intestinal microbiota
      of 33 infants of 1.5 to 18.5 months of age, associated with a panel of 8 probes
      targeting the predominant faecal bacterial groups of humans. The probes designed
      allowed detection and quantification of the relative proportions of C. difficile
      (0.5+/-1.0%) and C. perfringens (2.1+/-2.3%) in the microbiota of infants.

PMID- 16647149
TI  - Bioremediation of weathered-building stone surfaces.
AB  - Atmospheric pollution and weathering of stone surfaces in urban historic
      buildings frequently results in disfigurement or damage by salt crust formation
      (often gypsum), presenting opportunities for bioremediation using microorganisms.
      Conventional techniques for the removal of these salt crusts from stone have
      several disadvantages: they can cause colour changes; adversely affect the
      movement of salts within the stone structure; or remove excessive amounts of the
      original surface. Although microorganisms are commonly associated with
      detrimental effects to the integrity of stone structures, there is growing
      evidence that they can be used to treat this type of stone deterioration in
      objects of historical and cultural significance. In particular, the ability and
      potential of different microorganisms to either remove sulfate crusts or form
      sacrificial layers of calcite that consolidate mineral surfaces have been
      demonstrated. Current research suggests that bioremediation has the potential to
      offer an additional technology to conservators working to restore stone surfaces
      in heritage buildings.

PMID- 16647150
TI  - Environmental biocatalysis: from remediation with enzymes to novel green
      processes.
AB  - Modern biocatalysis is developing new and precise tools to improve a wide range
      of production processes, which reduce energy and raw material consumption and
      generate less waste and toxic side-products. Biocatalysis is also achieving new
      advances in environmental fields, from enzymatic bioremediation to the synthesis
      of renewable and clean energies and biochemical cleaning of 'dirty' fossil fuels.
      Despite the obvious benefits of biocatalysis, the major hurdles hindering the
      exploitation of the repertoire of enzymatic processes are, in many cases, the
      high production costs and the low yields obtained. This article will discuss
      these issues, pinpointing specific new advances in recombinant DNA techniques
      amenable to future biocatalyst development, in addition to drawing the attention
      of the biotechnology community to the active pursuit and development of
      environmental biocatalysis, from remediation with enzymes to novel green
      processes.

PMID- 16647151
TI  - Select the best: novel biocatalysts for industrial applications.
AB  - The number of biocatalysts needed for biotechnological applications is increasing
      rapidly, necessitating the development of novel identification systems. To date,
      strategies based on high-throughput screening and selection are applied, with the
      latter enabling a desired phenotype to survive under appropriate conditions. The
      groups of Witholt and de Lorenzo have devised a novel selection system,
      comprising a transcriptional regulator that is activated upon binding to the
      product of a biocatalytic reaction, which paves the way for easier selection of
      many different biocatalysts.

PMID- 16647152
TI  - Loco-regional recurrence after mastectomy in high-risk breast cancer--risk and
      prognosis. An analysis of patients from the DBCG 82 b&c randomization trials.
AB  - BACKGROUND AND PURPOSE: In the DBCG 82 b&c trials, 3,083 patients with stages II
      and III breast cancer were randomised to receive post-mastectomy radiotherapy
      (RT) versus no RT in addition to systemic therapy. The study showed a decrease in
      loco-regional recurrences and an improved survival in patients receiving RT. The
      aim of the present study was to identify risk factors for loco-regional
      recurrence (LRR), to evaluate the treatment of LRR and to examine the prognosis
      after LRR. PATIENTS AND METHODS: The 18-year probabilities of LRR were calculated
      for different prognostic factors using the Kaplan-Meier method. The efficacy of
      different LRR treatments was compared. The 5-year survival and distant metastases
      (DM) probability after LRR was calculated with regard to initial randomization
      group, primary tumor and recurrence related variables. RESULTS: Of the 3,083
      patients, 535 had a LRR alone as first site of failure. In univariate analyses,
      large primary tumor size, ductal carcinoma, high malignancy grade, fascia
      invasion, few removed nodes, many positive nodes and extracapsular invasion were
      all risk factors for developing LRR. Combined treatment with surgery and RT at
      the time of LRR increased the persistent loco-regional control. The 5-year
      probability of subsequent DM was 73% irrespective of initial randomization group.
      In multivariate analysis, large primary tumor size, many positive nodes,
      extracapsular invasion, supra/infraclaviculary failures, multiple LRR and a short
      interval less than 2 years to first LRR were poor prognostic factors for
      survival. CONCLUSIONS: Twenty-seven percent of LRR patients had no DM 5 years
      after failure. Initial randomization group did not alter the prognosis after LRR.
      Combined treatment of the LRR with surgery and RT improved persistent loco
      regional control compared with surgery or RT alone.

PMID- 16647153
TI  - Cardiac responses induced during thought-based control of a virtual environment.
AB  - Cardiac responses induced by motor imagery were investigated in 3 subjects in a
      series of experiments with a synchronous (cue-based) Brain-Computer Interface
      (BCI). The cue specified right hand vs. leg/foot motor imagery. After a number of
      BCI training sessions reaching a classification accuracy of at least 80%, the BCI
      experiments were carried out in an immersive virtual environment (VE), commonly
      referred as a "CAVE". In this VE, the subjects were able to move along a virtual
      street by motor imagery alone. The thought-based control of VE resulted in an
      acceleration of the heart rate in 2 subjects and a heart rate deceleration in the
      other subject. In control experiments in front of a PC, all 3 subjects displayed
      a significant heart rate deceleration of the order of about 3-5%. This heart rate
      decrease during motor imagery in a normal environment is similar to that observed
      during preparation for a voluntary movement. The heart rate acceleration in the
      VE is interpreted as effect of an increased mental effort to walk as far as
      possible in VE.

PMID- 16647154
TI  - Rapid concentration and purification of retrovirus by flocculation with
      Polybrene.
AB  - We have previously shown that the combined addition of Polybrene (PB) and
      chondroitin sulfate C (CSC) to retrovirus stocks leads to the formation of
      retrovirus-polymer complexes (i.e., flocs) that rapidly sediment onto cells,
      increases the efficiency of gene transfer, and can be used to rapidly concentrate
      and purify retrovirus stocks. The viruses remain associated with the
      polyelectrolyte complexes, however, which may complicate their use in downstream
      applications. In this study we determined if retrovirus could be flocculated
      using only one polymer (PB). We found that when retrovirus stocks were incubated
      with 320 microg/ml of PB, more than 70% of the viruses, and fewer than 0.3% of
      all other proteins, were pelleted by low-speed centrifugation. In contrast to
      retrovirus complexes formed with two polymers, retrovirus flocculated with PB
      disaggregated when they were resuspended in fresh medium. We conclude that
      flocculation of retroviruses with a single cationic polymer (PB) is a useful
      method for rapidly concentrating and purifying retroviruses, and may prove
      particularly useful when it is desirable to generate purified virus that is not
      part of a polymer complex.

PMID- 16647155
TI  - Drawing on international experience to reform the Belgian market for ostomy
      appliances.
AB  - This article aims to review the regulatory framework governing the Belgian ostomy
      appliance market in the light of the experience of Denmark, France, the
      Netherlands and Ontario (Canada) with regulation of ostomy appliances.
      Information about the regulatory framework was derived from the international
      literature, analysis of legal texts and a survey completed by national experts.
      The comparative analysis revealed that these countries have adopted varying
      approaches towards regulating their domestic ostomy appliance market. Strategies
      to keep down prices include public procurement in Denmark, maximum prices in
      France and exclusion of expensive appliances from reimbursement in the
      Netherlands. To contain public expenditure on ostomy appliances, consumption
      patterns are monitored in the Netherlands, the quantity of reimbursed appliances
      is limited in Belgium and public reimbursement is restricted in Ontario. Ostomy
      appliances are generally distributed by community pharmacies and medical
      equipment shops. In countries that emphasise home care delivery such as Denmark,
      domiciliary distributors dominate the market to the detriment of community
      pharmacies which do not seem to be able to offer this service at a competitive
      price. An avenue for reforming the Belgian ostomy appliance market is proposed
      which valorizes the role of ostomy care nurses in guiding the choice of ostomy
      appliances. Furthermore, it is recommended that a competitive tendering process
      determines the price of ostomy appliances, that reimbursement for service
      provision by distributors is separated from reimbursement of appliances, and that
      patients receive a fixed grant from the third-party payer to buy ostomy
      appliances.

PMID- 16647156
TI  - The choice of a health care provider in Eritrea.
AB  - The purpose of the study was to assess the factors that affect patients' choice
      of health care service providers and to analyse the effect of each factor, and to
      examine the policy implications for future health care provision in Eritrea. The
      data for this study was collected in a 10-month period from January to October
      2003. A total of 1657 households were included in the study. Our findings reveals
      that education, perceived quality, distance, user fees, severity of illness,
      socio-economic status and place of residence are statistically significant in the
      choice of a health care provider. Our study further shows that illness
      recognition is much lower for poor and less educated individuals. When an illness
      is recognized by the individual or household, a typical observation is that
      health care is less likely to be sought when the individual or household is poor
      and lives far from the facilities, and then only in case of a serious illness.
      Information on the choice of health care service providers is crucial for
      planning, organizing and evaluation of health services. The people's perception
      of disease/illness, their concept of health and the basis for their choice in
      health care has to be considered in order to respond with appropriate services
      and information, education and communication programs.

PMID- 16647157
TI  - Integral-based filtering of continuous glucose sensor measurements for glycaemic
      control in critical care.
AB  - Hyperglycaemia is prevalent in critical illness and increases the risk of further
      complications and mortality, while tight control can reduce mortality up to 43%.
      Adaptive control methods are capable of highly accurate, targeted blood glucose
      regulation using limited numbers of manual measurements due to patient discomfort
      and labour intensity. Therefore, the option to obtain greater data density using
      emerging continuous glucose sensing devices is attractive. However, the few such
      systems currently available can have errors in excess of 20-30%. In contrast,
      typical bedside testing kits have errors of approximately 7-10%. Despite greater
      measurement frequency larger errors significantly impact the resulting glucose
      and patient specific parameter estimates, and thus the control actions determined
      creating an important safety and performance issue. This paper models the impact
      of the continuous glucose monitoring system (CGMS, Medtronic, Northridge, CA) on
      model-based parameter identification and glucose prediction. An integral-based
      fitting and filtering method is developed to reduce the effect of these errors. A
      noise model is developed based on CGMS data reported in the literature, and is
      slightly conservative with a mean Clarke Error Grid (CEG) correlation of R=0.81
      (range: 0.68-0.88) as compared to a reported value of R=0.82 in a critical care
      study. Using 17 virtual patient profiles developed from retrospective clinical
      data, this noise model was used to test the methods developed. Monte-Carlo
      simulation for each patient resulted in an average absolute 1-h glucose
      prediction error of 6.20% (range: 4.97-8.06%) with an average standard deviation
      per patient of 5.22% (range: 3.26-8.55%). Note that all the methods and results
      are generalizable to similar applications outside of critical care, such as less
      acute wards and eventually ambulatory individuals. Clinically, the results show
      one possible computational method for managing the larger errors encountered in
      emerging continuous blood glucose sensors, thus enabling their more effective use
      in clinical glucose regulation studies.

PMID- 16647158
TI  - Potent anti-HIV activity of scytovirin domain 1 peptide.
AB  - Scytovirin (SVN) is a novel anti-HIV protein isolated from aqueous extracts of
      the cultured cyanobacterium Scytonema varium. SVN contains two apparent domains,
      one comprising amino acids 1-48 and the second stretching from amino acids 49 to
      95. These two domains display significant homology to each other and a similar
      pattern of disulfide bonds. Two DNA constructs encoding scytovirin 1-48 (Cys7Ser)
      (SD1) and 49-95 (Cys55Ser) (SD2) were constructed, and expressed in E. coli, with
      thioredoxin fused to their N-terminus. Purified recombinant products were tested
      for binding activities with the HIV surface envelope glycoproteins gp120 and
      gp41. Whole cell anti-HIV data showed that SD1 had similar anti-HIV activity to
      the full-length SVN, whereas SD2 had significantly less anti-HIV activity.
      Further deletion mutants of the SD1 domain (SVN(3-45)Cys7Ser, SVN(6-45)Cys7Ser,
      SVN(11-45)Cys7Ser) showed that the N-terminal residues are necessary for full
      anti-HIV activity of SD1 and that an eight amino acid deletion from the C
      terminus (SVN(1-40)Cys7Ser) had a significant effect, decreasing the anti-HIV
      activity of SD1 by approximately five-fold.

PMID- 16647159
TI  - Substituted 2-phenyl-benzimidazole derivatives: novel compounds that suppress key
      markers of allergy.
AB  - The pharmacotherapy of allergy and asthma has traditionally focused on the
      effecter molecules of the allergic cascade, while neglecting targets that play an
      early role in their development. Reasoning that IgE is central to the expansion
      of atopic diseases, we identified and extended a novel family of 2-(substituted
      phenyl)-benzimidazole inhibitors of IgE response. Pharmacological activity
      depends on an intact phenylbenzimidazole-bis-amide backbone, and is optimized by
      the presence of lipophilic terminal groups composed of either bis cycloalkyl or
      combinations of aliphatic and halogen-substituted aromatic groups. These
      compounds also inhibit IL-4 and IL-5 responses in T cells and CD23 expression on
      B cells, with potencies that parallel their inhibition of IgE. The broad profile
      of these compounds thus underscores their potential for treating the multifarious
      pathology of asthma.

PMID- 16647160
TI  - Synthesis, structure, toxicological and pharmacological investigations of 4
      hydroxycoumarin derivatives.
AB  - Twenty 4-hydroxycoumarin derivatives were synthesized. Five of them are described
      for the first time. The X-ray crystal structure analysis of 3,3'-(2,3,4
      trimethoxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (7) and 3,3'-(3,5
      dimethoxy-4-hydroxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (9)
      confirmed the structure of these compounds. A comparative pharmacological study
      of the anticoagulant effect with respect to Warfarin showed that the synthesized
      compounds have different anticoagulant activities. The most prospective compound
      is 3,3'-(4-chlorophenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (12) with
      low toxicity, very good index of absorption and dose dependent anticoagulant
      activity.

PMID- 16647161
TI  - Synthesis and evaluation of cytotoxic activity of arylfurans.
AB  - A series of 2-aryl and 2,5-diarylfurans were synthesized and evaluated for their
      in vitro cytotoxicity against human cancer cells lines and on the proliferation
      of human peripheral blood mononuclear cells (PBMC) stimulated with
      phytohemaglutinin (PHA). Three compounds were found to present significant
      activity against the cancer cell lines without affecting the lymphocyte
      proliferation in PBMCs, indicating low toxicity to normal cells.

PMID- 16647162
TI  - Syntheses and odor of "bulky group"-modified sandalwood odorants: isophorono-beta
      santalol analogues.
AB  - Three osmophoric points have been found to be necessary for the scent of
      sandalwood odorants. One of these points is the bulky group in a certain distance
      from the osmophoric hydroxyl group. Such a hydrophobic moiety is part of the
      trimethylcyclopentenyl derivatives, the so called campholenals, among them many
      are known to exert a strong and long lasting sandalwood odor. In continuation of
      our SAR-studies of sandalwood odorants four isophorone analogues of beta-santalol
      have been synthesized. The hydrophobic region of these new isophorone derivatives
      is now a trimethylcyclohexene nucleus, so to speak an extension of the
      cyclopentene part of the campholenals by one methylene group. This modification
      changes the sandalwood odor drastically to woody odor notes, reminiscent only to
      sandalwood odor. The environs of the crowded trimethylcyclohexene nucleus
      demonstrate the sensitivity of sandalwood odor on the shape of the hydrophobic,
      bulky part of beta-santalol analogues.

PMID- 16647163
TI  - Antiproliferative effect of Baylis-Hillman adducts and a new phthalide derivative
      on human tumor cell lines.
AB  - In this work we report our results concerning the study on the in vitro
      antiproliferative activity of 18 Baylis-Hillman adducts and some derivatives
      against a panel of humor tumor cell lines. A brief qualitative structure-activity
      relationship study indicated that carbon-carbon double bond and the presence of
      an electron-withdrawing substituent at the aromatic ring are essential for the
      activity. A quinoline-phthalide derivative has exhibited a potent effect on the
      proliferation of all cell lines. It is interesting to note their special
      cytotoxic activity against NCIADR cell line.

PMID- 16647164
TI  - Synthesis and antitumor activity of cis-dichloroplatinum(II) complexes of 1-(2
      aminophenyl)-1,2,3,4-tetrahydroisoquinolines.
AB  - Fifteen cis-dichloroplatinum complexes (5a-5o) were synthesized by treatment of 1
      (2-aminophenyl)-1,2,3,4-THIQs (4a-4o) with K(2)PtCl(4). The antitumor activity of
      these compounds was examined against four different human tumor cell lines. Their
      structure-activity relationships for antitumor activity are reported. All of
      these compounds exhibited activity against MCF-7 cell line and showed good
      activity against WiDr cell line except 5c and 5f. On the other hand, compounds 5j
      and 5o are more active than the other compounds against Hepa59T/VGH cell line.
      The electron-donating group at the 6-position of isoquinoline ring seems to
      decrease the antitumor activity and the chloro substituent at the C-4 position of
      the aniline ring shown the highest potency. The "trans influence" dominates the
      control of the stability of [1-(2-aminophenyl)-1,2,3,4
      THIQ]dichloroplatinums(II).

PMID- 16647165
TI  - Design, synthesis and in vivo anticonvulsant screening in mice of novel
      phenylacetamides.
AB  - A set of seven novel N-substituted 2-anilinophenylacetamides were designed by
      pharmacophore generation and using flexible alignment module of MOE software. The
      novel molecules were synthesized and screened for anticonvulsant activity in
      Swiss albino mice by MES and ScPTZ induced seizure tests. Test compounds were
      found to be potent in MES test. Compounds 12 and 14 were found to be more potent
      with ED(50) values 24.0 and 8.0 mg kg(-1), respectively, and their activity was
      comparable to standard drugs (Phenytoin, Carbamazepine). Test compounds did not
      show significant activity in ScPTZ test. Compounds 12 and 14 also exhibited
      higher protective indices (20.3 and 87.5, respectively) when assessed for
      neurotoxicity by rotarod test as compared to the standards.

PMID- 16647166
TI  - Solid-phase synthesis and pharmacological evaluation of a library of
      peptidomimetics as potential farnesyltransferase inhibitors: an approach to new
      lead compounds.
AB  - Oncogenic Ras proteins whose activation is farnesylation by farnesyltransferase
      have been seen as important targets for novel anticancer drugs. Inhibitors of
      this enzyme have already been developed as potential anti-cancer drugs,
      particularly by rational design based on the structure of the CA(1)A(2)X carboxyl
      terminus of Ras. Synthesis of a peptidomimetics library via solid-phase synthesis
      using the Multipin method is described here. The most active hits on cellular
      assays were resynthesized and enzymatic activity was measured. Compounds A1, A5
      and A7 present significant activity on the isolated enzyme (IC(50)=117, 57.3 and
      28.5 nM) and their molecular docking in the active site of the enzyme provides
      details on key interactions with the protein.

PMID- 16647167
TI  - [Central serous chorioretinopathy and systemic diseases report of 2 cases
      associated with corticotherapy].
AB  - INTRODUCTION: Central serous chorioretinopathy is an uncommon retinal disease,
      whose pathogenesis is largely unknown. It is characterized by an accumulation of
      subretinal fluid at the posterior pole of the fundus, creating a circumscribed
      area of serous retinal detachment. It manifests generally as a visual loss or an
      abnormal colour vision. It is often idiopathic but may also be associated with
      numerous pathological situations, with frequent exposure to corticosteroids.
      EXEGESIS: We report on two patients with central serous chorioretinopathy. The
      first female patient had been treated with steroids for a systemic lupus
      erythematosus for fifteen years, and the second male patient had been treated
      with steroids for an idiopathic hypereosinophilic syndrome for a few months.
      Visual loss led to a diagnosis of central serous chorioretinopathy. Lowering of
      steroids doses was followed by a clinical improvement in both cases. CONCLUSION:
      Similarly to cataract or glaucoma, central serous chorioretinopathy belongs to
      the potential ocular side-effect of steroid treatment, and thus deserves to be
      known by internists.

PMID- 16647168
TI  - [Is the seric eosinophil cationic protein level a valuable tool of diagnosis in
      clinical practice?].
AB  - SCOPE: The eosinophil cationic protein (ECP) is one of the mediators released
      during eosinophil activation. These cells are effector cells taking part into the
      Th2-lymphocyte dependent allergic inflammation. Assaying ECP concentrations in
      blood and sputum may be useful in evaluating allergic inflammation (asthma and
      rhinitis). This summary considers the value of measuring ECP levels for the
      diagnosis of various diseases where an eosinophil-mediated tissue inflammation
      plays a role. CURRENT SITUATION AND SALIENT POINTS: Levels of eosinophil cationic
      protein have been determined in nasal secretions, sputum, gastric secretions,
      feces and serum. They are increased during seasonal allergic rhinitis and
      perennial rhinitis, allergic asthma and atopic dermatitis. They are also
      increased in various gastro-intestinal disorders, some of which are associated
      with IgE: eosinophil intestinal diseases (esophagitis, gastro-enteritis and
      colitis), gastro-intestinal food allergy and intestinal parasitoses. Finally,
      they are increased in non IgE-dependent disorders: non allergic asthma with
      aspirin intolerance, respiratory infections, sinonasal polyposis, Churg-Strauss
      disease and idiopathic hyper-eosinophilia (HES) syndrome. PERSPECTIVES: Assaying
      serum ECP could help in the diagnosis of several diseases. With parasitic disease
      the pathogenic progression may be accurately assessed, when serological tests are
      less indicative. ECP assay may point to non allergic asthma, either Fernand-Widal
      syndrome or Churg-Strauss disease. As for gastro-intestinal disorders, it
      indicates an eosinophilic tissue reaction. In the event of isolated
      hypereosinophilia, ECP assay may clarify whether it is benign or tending towards
      idiopathic HES. The assay of peroxidase and eosinophil-derived neurotoxin (EDN)
      should be also considered.

PMID- 16647169
TI  - Immunity induced with a Salmonella enterica serovar Enteritidis live vaccine is
      regulated by Th1-cell-dependent cellular and humoral effector mechanisms in
      susceptible BALB/c mice.
AB  - The objective of this study was to characterize the immune response induced by a
      live attenuated Salmonella Enteritidis (SE; ade(-)/his(-)) vaccine using an
      intraperitoneal immunization/challenge model in susceptible wild-type and
      cytokine-deficient BALB/c mice. In wild-type mice, inoculation of the SE live
      vaccine induced a protective immune response characterized by both cellular
      (production of interleukin(IL)-12 and interferon(IFN)-gamma, granuloma formation
      in liver and spleen, DTH response) and humoral effector mechanisms (high antigen
      specific IgG2a titers). IL-12- and IL-4-deficient mice were immunized to study
      the individual roles of Th1 and Th2 cells, respectively. Protective immunity in
      wild-type mice required inoculation of >5 x 10(3)CFU of the attenuated live SE
      vaccine strain used. While IL-4-deficient mice developed a protective immune
      response similar to that found in wild-type mice, it was not possible to induce
      protective immunity in the highly susceptible IL-12-deficient mice due to severe
      disease symptoms and death following inoculation of the SE vaccine strain (doses
      >or=5 x 10(2)CFU were lethal for IL-12-deficient mice). Interestingly,
      persistence of the vaccine strain was observed in IL-4-deficient mice, indicating
      a role of IL-4 for clearance which, however, did not interfere with protective
      immunity. Together, the data indicate that the SE live vaccine activates a
      cellular and a humoral immune response, which are both regulated by Th1 cells via
      the secretion of IFN-gamma, whereas Th2 cells did not contribute essentially to
      the SE live-vaccine-induced immunity.

PMID- 16647170
TI  - A comparison of labour and birth experiences of women delivering in a birthing
      centre and at home in the Netherlands.
AB  - OBJECTIVE: to compare the labour and birth experiences of women who delivered at
      home without complications with the experiences of women who delivered in a birth
      centre without complications. DESIGN: a descriptive study using postal
      questionnaires at 1-6 months after birth of a consecutive sample of postpartum
      women. SETTING: women were recruited from one birth centre and three midwifery
      practices in an urban area of the Netherlands between September and December
      2003. PARTICIPANTS: 193 women; 129 delivered at home and 64 delivered in the
      birth centre. FINDINGS: the home-birth group perceived less pain (mean score home
      birth 6.291, birth-centre birth 6.977), desired less pain-relieving medication
      (home birth 7.9%, birth-centre birth 21.9%), believed they knew their midwife
      better (home birth 36%, birth-centre birth 10% 'knew her well'), and rated their
      birth setting 'higher' than the birth-centre group (mean score home birth 4.70,
      birth-centre birth 4.01). Furthermore, the birth-centre group emphasised safety,
      having medical help available, and convenience, whereas the home-birth group
      placed more importance on the home being trustworthy and dependable, having their
      own place and belongings, and feeling comfortable and relaxed. KEY CONCLUSIONS:
      having an understanding of a woman's labour and delivery experience allows health
      care providers to continue to improve the quality of maternity care. The
      environment can have a positive effect on a woman's birth experience;
      recommendations have been proposed that can be applied to all pregnant and
      labouring women. IMPLICATIONS FOR PRACTICE: identification and understanding of
      the factors in the environment that make the labour and birth experience more
      positive should be incorporated into the education and preparation for an
      upcoming birth.

PMID- 16647171
TI  - Increased nitrogen in runoff and soil following 13 years of experimentally
      increased nitrogen deposition to a coniferous-forested catchment at Gardsjon,
      Sweden.
AB  - Beginning in 1991, we have added nitrogen (N) to the 0.5-ha, N-poor, coniferous
      forested catchment G2 NITREX at Gardsjon, Sweden, to investigate the consequences
      of chronic elevated N deposition. We have added 40 kg N ha-1 yr-1 in fortnightly
      doses of NH4NO3 to the ambient 15 kg N ha-1 yr-1 by means of a sprinkling system.
      NO3 concentrations in runoff increased during 13 years from<1 to 70 microeq L-1,
      and in 2004 comprised about 10% of N input. Inhibition of NO3 immobilisation due
      to increased availability of NH4 might explain the increased leaching of NO3. C
      and N pools in the forest floor increased but C/N ratio has not changed. The
      increase in NO3 leaching thus occurred independently of change in C/N ratio. The
      results from Gardsjon demonstrate that increased leaching of inorganic N and
      decrease in C/N ratio respond to increased N deposition at greatly different time
      scales.

PMID- 16647172
TI  - Genotypic variations in the accumulation of Cd, Cu, Pb and Zn exhibited by six
      commonly grown vegetables.
AB  - Metal contaminants in garden and allotment soils could possibly affect human
      health through a variety of pathways. This study focused on the potential pathway
      of consumption of vegetables grown on contaminated soil. Five cultivars each of
      six common vegetables were grown in a control and in a soil spiked with Cd, Cu,
      Pb and Zn. Highly significant differences in metal content were evident between
      cultivars of a number of vegetables for several of the contaminants. Carrot and
      pea cultivars exhibited significant differences in accumulated concentrations of
      Cd and Cu with carrot cultivars also exhibiting significant differences in Zn.
      Distinctive differences were also identified when comparing one vegetable to
      another, legumes (Leguminosae) tending to be low accumulators, root vegetables
      (Umbelliferae and Liliaceae) tending to be moderate accumulators and leafy
      vegetables (Compositae and Chenopodiaceae) being high accumulators.

PMID- 16647173
TI  - Anxiety disorders and control related beliefs: the exemplar of Obsessive
      Compulsive Disorder (OCD).
AB  - Beliefs about control have been postulated to be important to anxiety and mood
      disorders. In particular, the phenomenology of Obsessive-Compulsive Disorder
      (OCD) suggests that it may be an exemplar of an anxiety disorder where control
      issues related to the self (behavior and thoughts) and world (the external
      environment) are particularly important. However, only beliefs concerning the
      need to control thoughts have been incorporated into contemporary theories of
      OCD. This article summarizes the theoretical and empirical research relevant to
      control-related beliefs in OCD. It is suggested that discrepancies between an
      individual's desired level of control and their perceived level of control could
      contribute to OCD symptoms, and exacerbate the tendency for individuals with OCD
      to engage in magical ideation and superstitious rituals. Overall, this review
      demonstrates how consideration of control cognitions could enhance our
      understanding of OCD and further improve its treatment.

PMID- 16647174
TI  - Parent communication and child pain and distress during painful pediatric cancer
      treatments.
AB  - Children with cancer often consider treatment procedures to be more traumatic and
      painful than cancer itself. Previous research indicates that parents' behavior
      before and during painful medical procedures influences children's distress
      level. Understanding parents' naturally occurring communication patterns is
      essential to identifying families in need of an intervention to enhance coping
      and emotional well-being. Using the concept of definition of the situation from a
      symbolic interactionism theoretical framework, this study developed a typology of
      parent communication patterns and tested relationships between those patterns and
      children's responses to potentially painful treatment procedures. Analyses are
      based on video-recorded observations of 31 children and their primary parents
      (individuals functioning in a parenting role and serving as the primary familial
      caregivers during the observed procedure) in the USA during clinic visits for
      potentially painful pediatric oncology treatments. Four communication patterns
      emerged: normalizing, invalidating, supportive, and distancing. The most common
      communication patterns differed by clinic visit phase: normalizing during pre
      procedure, supportive during procedure, and both distancing and supportive during
      post-procedure. Parents' communication also varied by procedure type. Supportive
      communication was most common during lumbar punctures; normalizing and distancing
      communication were most common during port starts. Six children (19.4%)
      experienced invalidation during at least one clinic visit phase. Analyses
      indicated that invalidated children experienced significantly more pain and
      distress than children whose parents used other communication patterns. This
      typology provides a theoretical approach to understanding previous research and
      offers a framework for the continuing investigation of the influence of parents'
      communication during potentially painful pediatric oncology procedures.

PMID- 16647175
TI  - Gray matter volume reduction in obsessive-compulsive disorder with schizotypal
      personality trait.
AB  - OBJECTIVES: Obsessive-compulsive disorder (OCD) with schizotypal personality
      trait (SPT) and OCD without SPT demonstrated differences in cognitive dysfunction
      and treatment response. This study aimed to investigate whether brain volume
      differs between OCD with SPT and OCD without SPT. METHODS: OCD with SPT (n=20),
      OCD without SPT (n=47), healthy comparison subjects (n=83) and schizophrenic
      patients (n=59) participated in this study. We assessed brain volume such as gray
      matter (GM), white matter (WM) and cerebrospinal fluid (CSF) using magnetic
      resonance imaging. The imaging data sets were filtered using anisotropic
      diffusion methods to improve the signal to noise ratio. The semi-automated region
      growing method was used to remove images of tissues exterior to the brain. The
      fuzzy C-means algorithm was used to segment the extracted brain images into gray
      matter, white matter and cerebrospinal fluid. RESULTS: OCD with SPT (p=0.048) and
      Schizophrenic patients (p<0.001) demonstrated a significant GM volume reduction
      compared to healthy controls. OCD without SPT revealed no significant GM volume
      reduction compared to healthy controls (p=0.504). CONCLUSION: This study suggests
      that OCD with SPT could be distinguished as a distinct subtype of OCD, based on
      observations of gray matter volume.

PMID- 16647176
TI  - Darwinian models of depression: a review of evolutionary accounts of mood and
      mood disorders.
AB  - Over the last ten years, there has been increased interest in the evolutionary
      origins of depressive phenomena. The current article provides a review of the
      major schools of thought that have emerged in this area. First, we consider
      important Darwinian explanations of depressed mood, including an integrative
      social risk hypothesis recently proposed by the authors. According to the social
      risk hypothesis, depression represents an adaptive response to the perceived
      threat of exclusion from important social relationships that, over the course of
      evolution, have been critical to maintaining an individual's fitness prospects.
      We argue, moreover, that in the ancestral environment, depression minimized the
      likelihood of exclusion by inducing: (i) cognitive hypersensitivity to indicators
      of social risk/threat; (ii) signaling behaviours that reduce social threat and
      elicit social support; and (iii) a generalized reduction in an individual's
      propensity to engage in risky, appetitive behaviours. Neurobiological support for
      this argument is also provided. Finally, we review three models that endeavour to
      explain the relationship between the adaptations that underlie depressed mood and
      clinically significant, depressed states, followed by a consideration of the
      merits of each.

PMID- 16647177
TI  - Oxidative metabolism of limbic structures after acute administration of diazepam,
      alprazolam and zolpidem.
AB  - The effects of acute administration of two benzodiazepines and a non
      benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats.
      After testing the behavioral action of the benzodiazepines on the open field and
      the elevated plus-maze, the effects of the three drugs on neuronal metabolism of
      particular limbic regions were measured using cytochrome c oxidase (CO)
      histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced
      clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg
      i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam
      were distinguishable from diazepam due to the pharmacological and clinical
      profile of this triazolobenzodiazepine. CO activity decreased significantly in
      almost all the limbic regions evaluated after zolpidem administration. However,
      significant prominent decreases in CO activity were found after diazepam
      treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate
      cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar
      decreases in CO activity, with the exception of the prelimbic and cingulate
      cortices, where significant increases were detected. In agreement with previous
      studies using other functional mapping techniques, our results indicate that
      particular benzodiazepines and non-benzodiazepine hypnotics induce selective
      changes in brain oxidative metabolism.

PMID- 16647178
TI  - Quercetin inhibition of ROS-dependent and -independent apoptosis in rat glioma C6
      cells.
AB  - In the present study, we investigated the protective mechanism of quercetin (QUE)
      and its glycosides, rutin (RUT) and quercitrin (QUI), on reactive oxygen species
      (ROS)-dependent (H(2)O(2)) and -independent (chemical anoxia) cell death in rat
      glioma C6 cells. Induction of HO-1 protein expression was detected in QUE- but
      not RUT- or QUI-treated C6 cells, and this was prevented by cycloheximide and
      actinomycin D. Incubation of C6 cells with QUE, but not RUT or QUI, protected C6
      cells from H(2)O(2)- and chemical anoxia-induced cytotoxicity according to the
      MTT and LDH release assays. Apoptotic characteristics including chromatin
      condensation, DNA ladders, and hypodiploid cells appeared in H(2)O(2)-and
      chemical anoxia-treated C6 cells, and those events were significantly suppressed
      by adding QUE (but not RUT or QUI). Increases in caspase 3, 8, and 9 enzyme
      activities with decreases in pro-PARP and pro-caspase 3 protein levels and an
      increase in cleaved D4-GDI protein were identified in H(2)O(2)-and chemical
      anoxia-treated C6 cells, and these were blocked by the addition of QUE, but not
      by RUT or QUI. Intracellular peroxide levels increased with H(2)O(2) and
      decreased with chemical anoxia, and the addition of QUE reduced the intracellular
      peroxide levels induced by H(2)O(2). Results of an anti-DPPH radical assay showed
      that QUE, RUT, and QUI dose-dependently inhibited the production of DPPH radicals
      in vitro; however, QUE (but not RUT or QUI) prevention of DNA damage induced by
      OH radicals was identified with a plasmid digestion assay. Increases in
      phosphorylated ERK and p53 protein expressions were detected in H(2)O(2)- but not
      chemical anoxia-treated C6 cells, and the addition of QUE significantly blocked
      H(2)O(2)-induced phosphorylated ERK and p53 protein expressions. Adding the HO-1
      inhibitors, SnPP, CoPP, and ZnPP, reversed the protective effect of QUE against
      H(2)O(2)- and chemical anoxia-induced cell death according to the MTT assay and
      morphological observations. Additionally, QUE exhibited inhibitory effects on
      LPS/TPA-induced transformation in accordance with a decrease in MMP-9 enzyme
      activity and iNOS protein expression in C6 cells. Taken together, the results of
      this study suggest that QUE exhibits an inhibitory effect on both ROS-dependent
      and -independent cell death, and induction of HO-1 protein expression is
      involved.

PMID- 16647179
TI  - Protective effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, on copper-induced hydroxyl radical generation in the rat
      heart.
AB  - The present study was examined the effect of fluvastatin, an inhibitor of 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on Cu(II)
      induced hydroxyl radical generation (OH) in the extracellular fluid of rat
      myocardium. Rats were anesthetized and sodium salicylate in Ringer's solution
      (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the
      generation of OH as reflected by the non-enzymatic formation of 2,3
      dihydroxybenzoic acid (DHBA) in the myocardium. When Cu(II) was infused through
      the microdialysis probe, Cu(II) increased in OH formation trapped as 2,3-DHBA in
      the dialysate. When fluvastatin (100 microM) was administered to Cu(II) (50
      microM)-pretreated animals, the levels of 2,3-DHBA at 300 min after
      administration of fluvastatin significantly decreased. In cumulative dose
      dependent experiments, three concentrations of Cu(II), 10, 25 and 50 microM, were
      infused through the microdialysis probe in the rat myocardium. A positive linear
      correlation between Cu(II) and the formation of 2,3-DHBA (R(2)=0.980) was
      observed. However, when corresponding experiments were performed with fluvastatin
      (100 microM) pretreated animals, the level of 2,3-DHBA decreased. These results
      suggest that blocking LDL oxidation by fluvastatin may attenuate Cu(II)-induced
      OH formation in the rat heart.

PMID- 16647180
TI  - Neurotransmitter inactivation is important for the origin of nerve system in
      animal early evolution: a suggestion from genomic comparison.
AB  - Metazoans possess complicated multicellular structure among the
      multicellularities of eukaryotes. One evolutionary pressure that permits such
      complexity relates to the directed and precise informational transmission
      performed by numerous synapses in neuron system. Neurotransmitter inactivations
      play essential roles in the termination of synaptic transmission and are thus
      crucial for precise synaptic transmission. Here, we performed a genomic
      comparison among 11 eukaryotic organisms including five bilaterian species and
      six pan-unicellular eukaryotes to search for genes related to metazoan
      multicellular function. The result showed that the majority of genes related to
      neurotransmitter inactivation in the synaptic cleft endured high and stable
      selective pressure and were specifically present in bilaterians, whereas genes
      related to transmitter release and postsynaptic transmitter receptors did not
      show these properties. From these data we conclude that neurotransmitter inaction
      may play a critical role in the origin of the nerve system encountered in the
      early evolution of metazoan. In addition, we suggest that neurotransmitter
      inactivation probably participates in the formation or refinement of the synapse,
      following the concept of "ontogeny recapitulates phylogeny." Further experimental
      evidence is needed to support the suggestion and to explain the importance of
      neurotransmitter inactivation to metazoan multicellular function.

PMID- 16647181
TI  - Plasticity from muscle to brain.
AB  - Recognition that the entire central nervous system (CNS) is highly plastic, and
      that it changes continually throughout life, is a relatively new development.
      Until very recently, neuroscience has been dominated by the belief that the
      nervous system is hardwired and changes at only a few selected sites and by only
      a few mechanisms. Thus, it is particularly remarkable that Sir John Eccles,
      almost from the start of his long career nearly 80 years ago, focused repeatedly
      and productively on plasticity of many different kinds and in many different
      locations. He began with muscles, exploring their developmental plasticity and
      the functional effects of the level of motor unit activity and of cross
      reinnervation. He moved into the spinal cord to study the effects of axotomy on
      motoneuron properties and the immediate and persistent functional effects of
      repetitive afferent stimulation. In work that combined these two areas, Eccles
      explored the influences of motoneurons and their muscle fibers on one another. He
      studied extensively simple spinal reflexes, especially stretch reflexes,
      exploring plasticity in these reflex pathways during development and in response
      to experimental manipulations of activity and innervation. In subsequent decades,
      Eccles focused on plasticity at central synapses in hippocampus, cerebellum, and
      neocortex. His endeavors extended from the plasticity associated with CNS lesions
      to the mechanisms responsible for the most complex and as yet mysterious products
      of neuronal plasticity, the substrates underlying learning and memory. At
      multiple levels, Eccles' work anticipated and helped shape present-day hypotheses
      and experiments. He provided novel observations that introduced new problems, and
      he produced insights that continue to be the foundation of ongoing basic and
      clinical research. This article reviews Eccles' experimental and theoretical
      contributions and their relationships to current endeavors and concepts. It
      emphasizes aspects of his contributions that are less well known at present and
      yet are directly relevant to contemporary issues.

PMID- 16647182
TI  - Environmental impacts of shore-parallel breakwaters along Nagahama and Ohgata,
      District of Joetsu, Japan.
AB  - A combination of sedimentological analysis of beach sands, field surveys and the
      assessment of the empirical methods for the breakwater design is used to
      investigate the impacts of offshore breakwaters on beach morphology along
      Nagahama and Ohgata. The results indicate that the nearshore sedimentation has
      been substantially disrupted due to the features formed behind the breakwaters
      stopping littoral transport, which led to sediment accretion on the updrift side
      of the breakwaters, and erosion on their downdrift side. Sedimentological
      analysis of beach sands made it possible to recognize the dominant process at the
      sections considered. In fact, the occurrence of strong offshore-going currents,
      the removal of finer mean grain size and the predominance of high-density heavy
      minerals led us to deduce that the two sections undergo a natural sedimentary
      imbalance.

PMID- 16647185
TI  - Against the motion: surgery is the best choice for Peyronie's disease.

PMID- 16647186
TI  - The motion: surgery is the best choice for Peyronie's disease.

PMID- 16647187
TI  - BPH treatment: a paradigm shift.

PMID- 16647188
TI  - Haemostasis in laparoscopy.
AB  - OBJECTIVE: Adequate haemostasis is essential for advanced laparoscopic procedures
      since uncontrolled bleeding may cause significant complications and even required
      converting to laparotomy to obtain sufficient haemostasis. The aim of this review
      is to give insight into the most important tools and strategies to achieve
      sufficient haemostasis during advanced urologic laparoscopy. METHODS AND RESULTS:
      Lowering the risk of haemorrhage may be achieved primarily by proper case
      selection, resulting in adequate laparoscopic preparation and dissection
      technique or the use of local compression by sponge stick to control local
      bleeding. For early bleeding control, laparoscopic clip appliers, staplers and
      suturing techniques may be utilised. Various energy sources such as monopolar and
      bipolar electrocautery, argon beam coagulators, laser or ultrasonic dissectors
      and topical sealing agents can be used to augment natural haemostasis.
      CONCLUSIONS: A wide armamentarium for achieving haemostasis during laparoscopy is
      available. Consequently, laparoscopic surgeons must have detailed knowledge of
      the physical concepts of each surgical instrument or energy source and of proper
      use of tissue sealants for obtaining sufficient haemostasis. This knowledge will
      improve postoperative outcome, increase patient safety and guide laparoscopic
      techniques to further perspectives.

PMID- 16647189
TI  - For the motion: surgery is the best choice for Peyronie's disease.

PMID- 16647191
TI  - Transcriptional regulation of the insulin-like growth factor-I receptor gene in
      breast cancer.
AB  - The insulin-like growth factor-I receptor (IGF-IR) has an important role in
      normal mammary gland growth and morphogenesis. In addition, the IGF-IR has been
      implicated in the initiation and progression of breast cancer. Previous studies
      have indicated that acquisition of the malignant phenotype in breast cancer is
      initially IGF-IR dependent. Most breast cancer-derived cell lines and primary
      tumors express high levels of IGF-IR mRNA and protein, whereas metastatic stages
      are usually associated with a decrease in IGF-IR levels. Transcription of the IGF
      IR gene is controlled by complex interactions involving DNA-binding and non DNA
      binding transcription factors. This review highlights selected examples of tumor
      suppressors, including BRCA1, p53, and WT1, whose mechanism of action involves
      regulation of IGF-IR gene expression.

PMID- 16647192
TI  - Canavan disease and the role of N-acetylaspartate in myelin synthesis.
AB  - Canavan disease (CD) is an autosomal-recessive neurodegenerative disorder caused
      by inactivation of the enzyme aspartoacylase (ASPA, EC 3.5.1.15) due to
      mutations. ASPA releases acetate by deacetylation of N-acetylaspartate (NAA), a
      highly abundant amino acid derivative in the central nervous system. CD results
      in spongiform degeneration of the brain and severe psychomotor retardation, and
      the affected children usually die by the age of 10. The pathogenesis of CD
      remains a matter of inquiry. Our hypothesis is that ASPA actively participates in
      myelin synthesis by providing NAA-derived acetate for acetyl CoA synthesis, which
      in turn is used for synthesis of the lipid portion of myelin. Consequently, CD
      results from defective myelin synthesis due to a deficiency in the supply of the
      NAA-derived acetate. The demonstration of the selective localization of ASPA in
      oligodendrocytes in the central nervous system (CNS) is consistent with the
      acetate deficiency hypothesis of CD. We have tested this hypothesis by
      determining acetate levels and studying myelin lipid synthesis in the ASPA gene
      knockout model of CD, and the results provided the first direct evidence in
      support of this hypothesis. Acetate supplementation therapy is proposed as a
      simple and inexpensive therapeutic approach to this fatal disease, and progress
      in our preclinical efforts toward this goal is presented.

PMID- 16647193
TI  - Protein/DNA interaction profiling reveals novel regulators of the pineal
      transcriptome.
AB  - The rat pineal gland transcriptome exhibits dynamic daily variation that reflects
      nocturnally restricted hormone production. Here we have used a protein/DNA
      interaction array to screen for day-night changes in DNA binding activity that
      are associated with transcriptional rhythms. Overall, 47 of 54 potential
      consensus binding sequence activities were detected, and of these, 29 (62%) were
      found to exhibit day:night differences in level. In addition to known, rhythmic
      pineal DNA binding activities (CRE and AP-1), multiple novel activities were
      observed including nocturnally elevated AP-2 consensus sequence binding activity.
      This array result was validated using conventional DNA binding assays, and we
      have also demonstrated AP-2beta and AP-2gamma proteins in the pineal gland, in
      addition to a nocturnally elevated AP-2alpha isoform. Our results have confirmed
      the presence of a complex assembly of transcriptional rhythms in the rat pineal
      gland and have provided details of more factors that contribute to this aspect of
      circadian neuroendocrine function.

PMID- 16647194
TI  - Meiotic arrest of oocytes depends on cell-to-cell communication in the ovarian
      follicle.
AB  - The source of the inhibitory levels of cAMP that maintain oocytes meiotically
      arrested is under controversy. A model for regulation of the meiotic division
      that suggests the transfer of a somatic follicular cells-derived cAMP into the
      oocyte via gap junctions was first proposed by us in 1978. Later studies provide
      strong evidence that established gap-junctional communication within the ovarian
      follicle is indispensable for maintenance of meiotic arrest. On the other hand,
      other recent reports suggest that oocytes generate their own inhibitory cAMP by a
      G protein-coupled receptor-activated Gs. These studies as well as other recent
      reports related to this topic are thoroughly discussed in this chapter.

PMID- 16647195
TI  - Decoding the nightly melatonin signal through circadian clockwork.
AB  - Photoperiod regulates the timing of seasonal cycles in reproduction, energy
      metabolism, moult and other seasonal characteristics, and the effects are
      transduced through changes in the duration of nocturnal melatonin secretion from
      the pineal gland. Short daily melatonin signals (4-8 h/day) activate a summer
      physiology, while long signals (> 10 h/day) produce a winter phenotype. Decoding
      signal duration occurs in specific target cells in the brain and pituitary gland,
      each governing a different component of the seasonal adaptation. The pars
      tuberalis (PT) of the pituitary regulates prolactin release and provides a
      tractable model system to investigate the molecular decoding mechanism. In the
      PT, melatonin onset at dusk activates cryptochrone (Cry1) gene expression and
      melatonin offset at dawn activates period (Per1) gene expression, thus the
      Cry/Per interval varies directly with nightlength, and inverse to daylength. It
      is proposed that photoperiod-induced changes in this phase-relationship dictates
      the level of CRY/PER protein heterodimer formation, and in turn, the level of
      transcriptional drive to the genes that control PT output--up-regulated under
      long days stimulating prolactin secretion and a summer physiology, and--down
      regulated by short days in winter. The melatonin signal is thus decoded through
      circadian clock genes.

PMID- 16647196
TI  - Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently
      of the growth hormone secretagogue receptor type 1a and the corticotropin
      releasing factor 2 receptor.
AB  - Both unacylated ghrelin (UAG) and acylated ghrelin (AG) exert metabolic effects.
      To investigate the interactions between AG and UAG on ghrelin receptors we
      evaluated the effects of AG and UAG on INS-1E rat insulinoma cells, using insulin
      secretion after 30min static incubation as a read-out. A possible involvement of
      the growth hormone secretagogue receptor type 1a (GHS-R1a) or the corticotropin
      releasing factor 2 (CRF2) receptor (CRF2R), as a putative receptor for UAG, was
      also studied determining their mRNA expression and the functional effects of
      receptor antagonists on insulin release. Both UAG and AG stimulated insulin
      release dose-dependently in the nanomolar range. The AG-induced insulin output
      was antagonized by two GHS-R1a antagonists ([d-Lys(3)]GHRP-6 and BIM28163), which
      did not block UAG actions. These effects occurred in the presence of low levels
      of GHS-R1a mRNA. Neither CRF2R expression nor effects of the CRF2R antagonist
      (astressin(2)B) on insulin output were observed. In conclusion, we provide a
      sensitive and reproducible assay for specific effects of UAG, which in this study
      is responsible for insulin release by INS-1E cells. Our data support the
      existence of a specific receptor for UAG, other than the CRF2R and GHS-R1a. The
      stimulatory effect on insulin secretion by AG in this cell line is mediated by
      the GHS-R1a.

PMID- 16647197
TI  - Sperm capacitation is regulated by the crosstalk between protein kinase A and C.
AB  - The binding of capacitated sperm to the egg's zona pellucida stimulates it to
      undergo the acrosome reaction, a process which enables the sperm to penetrate the
      egg. Mammalian sperm capacitation and the acrosome reaction require remodeling of
      actin filaments. An increase in phospholipase D (PLD)-dependent actin
      polymerization occurs during capacitation whereas the increase in sperm
      intracellular calcium after its binding to the egg causes very fast actin
      depolymerization prior to the acrosome reaction. Protein kinase A (PKA) and C
      (PKC) can both activate sperm PLD and actin polymerization under in vitro
      incubation, however under physiological conditions, actin polymerization depends
      primarily on PKA activity. We suggest that PKA indirectly activates
      phosphatidylinositol 4-kinase to produce phosphatidylinositol 4,5-bisphosphate
      which is a cofactor for PLD activation. In addition, activation of PKA during
      capacitation inactivates phospholipase C resulting in preventing PKC activation.
      It appears that PKA activation promotes sperm capacitation whereas too early
      activation of PKC during capacitation would jeopardize this process. Thus, a
      refined balance between the two pathways is required for optimal and sustained
      activation during sperm capacitation.

PMID- 16647198
TI  - Short course of albendazole therapy for neurocysticercosis.

PMID- 16647199
TI  - Traumatic intraspinal extradural ganglion cyst in a teenager: case report and
      review of the literature.
AB  - Spinal extradural cyst is a rare cause of spinal cord or nerve root compression.
      We present a case which is unique due to both the young age of the patient and
      its distinctly acute haemorrhagic presentation. In what is normally considered a
      degenerative disease in older patients this has implications for the possibility
      of a traumatic aetiology in children. The literature on the classification of
      extradural cysts is reviewed.

PMID- 16647200
TI  - Highlights in experimental therapeutics.
AB  - The past two decades have seen a dramatic change in cancer treatment paradigms.
      Anticancer agents are no longer being developed based on empiricism and
      serendipity, but are now being aimed to inhibit a validated target that is
      relatively specific for tumours rather than normal cells. The vast majority of
      cancers arise from multiple genetic lesions; thus, sophisticated drug cocktails,
      or single drugs acting on multiple downstream targets will be needed for
      successful cancer therapy. Three emerging concepts that are addressing these
      therapeutic needs and that are key to blocking steps in tumourigenesis will be
      highlighted in this review: (a) attacking cancer cell immortality by targeting
      the telomere/telomerase complex; (b) targeting oncogene activation by inhibiting
      the molecular chaperone Hsp90; and (c) stabilizing tumour suppressor proteins by
      modulating the ubiquitin-proteasome system.

PMID- 16647201
TI  - Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer
      cell line with epigenetic modifiers and ganciclovir.
AB  - Epstein-Barr virus (EBV) is an oncogenic herpes virus. EBV gene transcription is
      regulated by an epigenetic mechanism to establish a persistent infection and to
      evade the host immune system. We found that low concentrations of epigenetic
      modifying agents, 5-aza-2'-deoxycytidine (5-aza-CdR) or trichostatin A (TSA),
      induced the expression of BMRF1, BZLF1, and BRLF1 genes, which are found in the
      lytic form of the virus, in an EBV-positive gastric cancer cell line. This effect
      did not involve PI3 kinase, MAP/ERK kinase, protein kinase C delta, or p38 MAPK
      signaling pathway. The cytotoxic effect of ganciclovir (GCV) was enhanced after
      the lytic induction by epigenetic modifiers, and the combination of GCV and
      epigenetic modifiers induced apoptosis, which is dependent on caspases. In
      conclusion, the combination of GCV with 5-aza-CdR or TSA might be a useful
      therapeutic strategy for EBV-induced human gastric cancer.

PMID- 16647202
TI  - Copper(II)-rubeanic acid coprecipitation system for separation-preconcentration
      of trace metal ions in environmental samples for their flame atomic absorption
      spectrometric determinations.
AB  - A simple and facile preconcentration procedure based on the coprecipitation of
      trace heavy metal ions with copper(II)-rubeanic acid complex has been developed.
      The analytical parameters including pH, amounts of rubeanic acid, sample volume,
      etc. was investigated for the quantitative recoveries of Pb(II), Fe(III), Cd(II),
      Au(III), Pd(II) and Ni(II). No interferic effects were observed from the
      concomitant ions. The detection limits for analyte ions by 3 sigma were in the
      range of 0.14 microg/l for iron-3.4 microg/l for lead. The proposed
      coprecipitation method was successfully applied to water samples from Palas Lake
      Kayseri, soil and sediment samples from Kayseri and Yozgat-Turkey.

PMID- 16647203
TI  - Thermal treatment of the fly ash from municipal solid waste incinerator with
      rotary kiln.
AB  - Reuse of the fly ash from the municipal solid waste incinerator (MSWI) is a
      policy of Taiwan EPA. However, the fly ash is often classified as a hazardous
      waste and cannot be reused directly because the concentrations of heavy metals
      exceed the TCLP regulations. The main objective of this study is to investigate
      the continuous sintering behavior of fly ash with a rotary kiln and seek a
      solution to reduce the concentrations of heavy metal to an acceptable value. The
      partitions of the heavy metals in the process are also considered. The results of
      TCLP showed that among the metals of Cr, Cd, Cu and Pb, only the concentrations
      of Pb in raw fly ash exceeded the regulation. At sintering temperatures of 700,
      800 and 900 degrees C, the concentration of Pb decreased in sintering products,
      however, the concentration of Pb still exceeded the limitation at 700 and 800
      degrees C. Additionally, the water-washing was used to pre-treat the fly ash
      before sintering process. The washing treatment effectively reduced the leaching
      concentrations of Pb to agree the regulations. Therefore, water-washing followed
      by a sintering treatment is an available process for detoxifying the fly ash of
      MSWI.

PMID- 16647204
TI  - Effect of quaternary ammonium cation loading and pH on heavy metal sorption to Ca
      bentonite and two organobentonites.
AB  - Sorption of four heavy metals (Pb, Cd, Zn and Hg) to calcium bentonite (Ca
      bentonite), hexadecyltrimethylammonium bentonite (HDTMA bentonite) and
      benzyltriethylammonium bentonite (BTEA bentonite) was measured as a function of
      the quaternary ammonium cation (QAC) loading at 25, 50 and 100% of the clay's
      cation-exchange capacity (CEC). The effects of pH on the surface charge of the
      clays and heavy metal sorption were also measured. Sorption of Cd, Pb, and Zn was
      non-linear and sorption of all three metals by HDTMA and BTEA bentonites
      decreased as the QAC loading increased from 25 to 100%. In most cases, sorption
      of these metals to 25% BTEA and 25% HDTMA bentonite was similar to or greater
      than sorption to Ca bentonite. Hg sorption was linear for both HDTMA and BTEA
      bentonite. No significant effect on Hg sorption was observed with increasing QAC
      loading on BTEA bentonite. However, an increase of Hg sorption was detected with
      increasing QAC loading on HDTMA bentonite. This behavior suggests that a process
      different than cation exchange was the predominant Hg sorption mechanism. Cd, Pb,
      and Zn sorption decreased with pH. However, this effect was stronger for Cd and
      Pb than Zn. Hg sorption varied inversely with pH. QAC loading affected the
      surface charge of the clays. Twenty-five and 50% loading of BTEA cations
      increased the negative charge on the clay's surface relative to the untreated
      clay, without affecting the zero point of charge (ZPC) of the clay. Increased QAC
      loading on HDTMA bentonite causes the surface charge to become more positive and
      the ZPC increased. One hundred percent of HDTMA bentonite maintained a positive
      surface charge over the range of pH values tested. The organoclays studied have
      considerable capacity for heavy metal sorption. Given that prior studies have
      demonstrated the strong sorption capacity of organoclays for nonionic organic
      pollutants, it is likely that organoclays can be useful sorbents for the
      treatment of effluent streams containing both organic contaminants and heavy
      metals.

PMID- 16647205
TI  - Study of the removal of dichlorvos and dimethoate in a titanium dioxide mediated
      photocatalytic process through the examination of intermediates and the reaction
      mechanism.
AB  - The photocatalytic oxidation of two selected organophosphorous insecticides
      (dichlorvos and dimethoate) has been investigated. The aim of the study was the
      identification of the intermediates that are formed during photocatalytic
      treatment. Intermediate products from the slurry system were identified by means
      of solid-phase extraction (SPE) coupled to gas chromatography-mass spectroscopy
      techniques (GC-MS). Nine possible by-products were identified for dimethoate and
      three for dichlorvos. A proposed degradation pathway for each insecticide is
      presented, involving mainly oxidation and dealkylation reactions. The results
      demonstrated that some of the transient intermediates formed (oxon derivatives,
      disulfide, chlorinated fragments), were more toxic compared to parent compounds
      whereas most of them are less toxic than the parent compounds.

PMID- 16647206
TI  - Column study on Cr(VI)-reduction using the brown seaweed Ecklonia biomass.
AB  - The potential use of the brown seaweed, Ecklonia, biomass as a bioreductant for
      reducing Cr(VI) was examined in a continuous packed-bed column. The effects of
      the operating parameters, such as influent Cr(VI) concentration, influent pH,
      biomass concentration, flow rate and temperature, on the Cr(VI) reduction were
      investigated. Increases in the influent Cr(VI) concentration and flow rate or a
      decrease in the biomass concentration inside the column led to a higher
      breakthrough of the Cr(VI) ions in the effluent. Particularly, the influent pH
      and temperature most significantly affected on the breakthrough curve of Cr(VI);
      a decrease in the influent pH or an increase in the temperature enhanced the
      Cr(VI) reduction in the column. For process application, a non-parametric model
      using neural network was used to predict the breakthrough curves of the column.
      Finally, the potential of the column packed with Ecklonia biomass for Cr(VI)
      detoxification was demonstrated.

PMID- 16647207
TI  - Decision support tool for used oil regeneration technologies assessment and
      selection.
AB  - Regeneration is the most efficient way of managing used oil. It saves money by
      preventing costly cleanups and liabilities that are associated with mismanagement
      of used oil, it helps to protect the environment and it produces a technically
      renewable resource by enabling an indefinite recycling potential. There are a
      variety of processes and licensors currently offering ways to deal with used
      oils. Selecting a regeneration technology for used oil involves "cross-matching"
      key criteria. Therefore, the first prototype of spent oil regeneration (SPORE), a
      decision support tool, has been developed to help decision-makers to assess the
      available technologies and select the preferred used oil regeneration options.
      The analysis is based on technical, economical and environmental criteria. These
      criteria are ranked to determine their relative importance for a particular used
      oil regeneration project. The multi-criteria decision analysis (MCDA) is the core
      of the SPORE using the PROMETHEE II algorithm.

PMID- 16647208
TI  - Numerical model to predict settlements coupled with landfill gas pressure in
      bioreactor landfills.
AB  - Landfills settle due to its weight and biodegradation of waste. Biodegradation
      induced settlement is a direct result of rearrangement of waste skeleton in
      response to the conversion of waste mass into landfill gases. Traditionally, the
      compressibility index based on settlement of clays is used to explain the
      settlement of waste. Literature review showed that there are limited research
      attempts of landfill settlement predictions by coupling with landfill gas
      generation and transport. This research describes a model which couples
      settlement in a bioreactor landfill with the generation and subsequent upward
      movement of landfill gases. The mass balance of the landfill gas was used to link
      settlement and gas pressures. In the absence of a closed-formed analytical
      solution, a computer program was developed to numerically predict the settlements
      and gas pressures in a bioreactor landfill using landfill geometry and waste
      properties. Explicitly computed settlement values were then used to predict the
      pressure profile implicitly. To test the mathematical formulations, a numerical
      exercise was performed using a single-cell hypothetical bioreactor landfill. The
      numerical simulation produced satisfactory trends of the settlement and the
      landfill gas pressure profiles.

PMID- 16647209
TI  - Topical ketanserin attenuates hyperalgesia and inflammation in arthritis in rats.
AB  - We investigated effects of topical application of ketanserin, a 5-HT2A receptor
      antagonist, on hyperalgesia and edema in the arthritic rat, a chronic pain model
      with inflammation. Unilateral, but not bilateral, arthritis was induced with
      intra-articular injection of a mixture of kaolin and carrageenan in one side, as
      indicated by the shortened paw withdrawal latency and an increase in the
      circumference of the knee joint. Topical application of ketanserin onto skin over
      the arthritic joint delivered in a mixture of gelatin, glycerol and kaolin
      produced dose-dependent attenuation of nociceptive and inflammatory effects
      resulting from intra-articularly injected kaolin/carrageenan. One and 3%
      ketanserin produced significant or even complete anti-hyperalgesia, as well as a
      remarkable anti-inflammatory effect (50-70% reduction of edema) while 0.3%
      ketanserin and placebo failed to produce any effect. Moreover, the effects of
      ketanserin were maintained for 13 days without decline. In contrast, 3%
      ketanserin applied to skin of the knee joint on the non-inflamed side for 2 weeks
      did not alter nociceptive thresholds of the paw and the size of the knee joint in
      both the inflamed and non-inflamed limbs. These results indicate that 5-HT2A
      receptors in the periphery play a significant role in the maintenance and/or
      development of inflammatory pain. The present study suggests that topical
      ketanserin is a promising direction for potential clinical exploration to relieve
      established hyperalgesia and inflammation in arthritis without adverse effects
      and tolerance.

PMID- 16647210
TI  - Prevalence of Giardia and Cryptosporidium in dairy calves in three areas of
      Norway.
AB  - A study was undertaken to determine the prevalences of Cryptosporidium and
      Giardia in dairy calves less than 6 months of age in Norway. Faecal samples were
      collected from a total of 1386 calves, between 3 and 183 days of age, in 136
      dairy farms from three different areas of Norway. Faecal samples were examined
      for Cryptosporidium oocysts and Giardia cysts after concentration and
      immunofluorescent staining. Giardia was found in 93% (127 out of 136) of the
      farms and in 49% (679 out of 1386) of the calves. Cryptosporidium was found in
      53% (72 out of 136) of the farms and in 12% (167 out of 1386) of the calves. The
      level of Giardia and/or Cryptosporidium was low in the majority of the infected
      calves. Infection peaked in the age group 2-3 months for both Cryptosporidium and
      Giardia. The prevalences of both parasites were higher in samples taken during
      winter than in samples taken during summer, and statistically significant
      differences were found when prevalences in different age groups of calves were
      compared between the three areas. A significantly lower prevalence of
      Cryptosporidium was found in calves housed in shared pens that were thoroughly
      washed more than three times a year than in calves from pens washed less often.
      For Giardia there was a trend for decreasing intensity of infection with
      increasing age in the sampled calves. For Cryptosporidium there was a trend for
      increasing herd prevalence with increasing number of calves in the herd, but this
      trend was not statistically significant. Other parameters which were investigated
      such as housing, feeding or management routines were not associated with
      prevalence or intensity of infection with either parasite.

PMID- 16647211
TI  - Epidemiological survey of swine cysticercosis using ante-mortem and post-mortem
      examination tests in the southern highlands of Tanzania.
AB  - Pig keeping is known to be popular in the regions of the southern highlands zone
      (Mbeya, Iringa and Ruvuma) of Tanzania where more than 60% of pigs under the
      small-scale production system are raised. However, no epidemiological surveys on
      porcine cysticercosis have been conducted in the zone in spite of unofficial
      reports indicating the disease to be a widespread problem. To estimate prevalence
      rates and risk factors for porcine cysticercosis in Chunya and Iringa Rural
      Districts and Ruvuma Region (Songea and Mbinga Districts), 722, 808 and 302 live
      pigs, respectively, were examined by lingually and the prevalence of swine
      cysticercosis was found to be 7.6%, 8.4% and 16.9% for Chunya and Iringa Rural
      Districts, and Ruvuma Region, respectively. Structured observations and
      questionnaire interviews were used to analyse pig rearing practices and household
      use of latrines in Chunya and Iringa Rural Districts only. The analysis of effect
      of pig management practices, lack of a latrine, eating undercooked pork, home
      slaughter and no inspection of pork and lack of knowledge of T. solium on their
      association to tongue positivity in pigs was done by means of a contingency
      table. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) and
      p-values were calculated. Structured questionnaire interviews identified factors
      associated with the disease prevalence in both Chunya and Iringa Rural Districts
      were free-ranging of pigs, home slaughtering of pigs and pork not being
      inspected. While in Chunya and Iringa Rural Districts lack of latrine and
      barbecuing were found a risk factor, respectively. To control the disease in the
      study areas of the southern highlands there is a need for significant
      improvements regarding the use of latrines, confinement of pigs, pork inspection
      and thorough cooking of pork.

PMID- 16647212
TI  - Comparative infectivity of oocysts and bradyzoites of Toxoplasma gondii for
      intermediate (mice) and definitive (cats) hosts.
AB  - Tachyzoites, bradyzoites (in tissue cysts), and sporozoites (in oocysts) are the
      three infectious stages of Toxoplasma gondii. The prepatent period (time to
      shedding of oocysts after primary infection) varies with the stage of T. gondii
      ingested by the cat. The prepatent period (pp) after ingesting bradyzoites is
      short (3-10 days) while it is long (18 days or longer) after ingesting oocysts or
      tachyzoites. The conversion of bradyzoites to tachyzoites and tachyzoites to
      bradyzoites is biologically important in the life cycle of T. gondii and it has
      been proposed that the pp can be used to study stage conversion. In the present
      study, infectivity of oocysts and bradyzoites released from tissue cysts of a
      recent isolate of T. gondii, TgCkAr23, to cats and mice was compared. Ten-fold
      dilutions of oocysts or bradyzoites were administered orally to cats, and orally
      and subcutaneously to mice. Of the 29 cats each fed 1-10 million oocysts only one
      cat shed oocysts and the pp was 23 days; all cats remained asymptomatic. In
      contrast, all mice administered the same 10-fold dilutions of oocysts either
      orally or subcutaneously died of toxoplasmosis. The results confirm that
      infectivity of the oocysts to cats is lower than for mice and that oocysts are
      non-pathogenic for cats. Of the 41 cats each fed 1-1,000 free bradyzoites, 15
      shed oocysts with a short pp of 4-9 days, and all remained asymptomatic. The
      infectivity of bradyzoites to mice by the oral route was approximately 100 times
      lower than that by the subcutaneous route. The results confirm the hypothesis
      that the pp in cats is stage and not dose dependent, and that transmission of T.
      gondii is most efficient when cats consume tissue cysts (carnivory) or when
      intermediate hosts consume oocysts (fecal-oral transmission).

PMID- 16647213
TI  - Motivation for change and the pros and cons of smoking in a Spanish population.
AB  - Decisional balance and the stage of change have been used to understand the
      motivation for giving up the habit of smoking. The objective of this study was to
      find out whether the associations between the pros and the cons of smoking,
      taking into account the magnitude and delay parameters, and stages of change, can
      be demonstrated in a sample of Spanish smokers and ex-smokers using a cross
      sectional design. The results are compared with the patterns of pros and cons of
      smoking found in samples of American, Swiss and Dutch smokers. The data confirms
      that amongst Spanish smokers it is also in the stages of contemplation and
      preparation that the crossover in the valuation of the pros and cons of smoking
      takes place: the cons hold more weight than the pros. On the other hand,
      unexpectedly, the pros of smoking are more highly valued in the stages of action
      and maintenance than in the rest of the stages.

PMID- 16647214
TI  - Question-based assessments of delay discounting: do respondents spontaneously
      incorporate uncertainty into their valuations for delayed rewards?
AB  - This research was designed to determine if, and to what extent, participants
      incorporate uncertainty into their valuations for delayed rewards when completing
      measures of delay discounting, even though uncertainty is not specified in the
      delay-discounting questions. Twenty-four adolescent participants completed a
      question-based measure of delay discounting and immediately following answered
      questions about perceived certainties of receiving the delayed rewards. Results
      showed that respondents rated the delayed rewards as increasingly uncertain with
      longer delays. Also, ratings of uncertainty were correlated with rate of delay
      discounting (r=0.55). These findings suggest participants automatically evaluate
      delayed rewards as uncertain when using this assessment procedure. The current
      finding may hold important implications for future addiction research in
      interpreting why addicted persons often discount more by delay than non-addicted
      controls, i.e., delay to reward or uncertainty about delayed rewards?

PMID- 16647215
TI  - Evaluating a method of assessing competence in Motivational Interviewing: a study
      using simulated patients in the United Kingdom.
AB  - In this evaluation of a method of assessing competence in Motivational
      Interviewing (MI), participants were asked to interview an actor simulating a
      substance abuser who was ambivalent about an important issue. The interviews were
      videotaped and subsequently rated for competence in MI using the Motivational
      Interviewing Treatment Integrity code (MITI). Ratings of 43 interviews made
      independently by trained judges found high levels of inter-rater agreement.
      Ratings of 11 pairs of interviews carried out by the same interviewer with
      different simulated patients, a mean of 26days apart, resembled each other
      closely. Participants who had been trained in MI were significantly more
      competent than others. There was a significant association between researchers'
      and patients' ratings of the extent to which the interviewer demonstrated the
      spirit of MI. These findings imply that the assessment method produces reasonably
      reliable and valid ratings of competence in MI and can be used for both clinical
      and research purposes.

PMID- 16647216
TI  - Measurement properties of the Fagerstrom Test for nicotine dependence adapted for
      use in an adolescent sample.
AB  - This study uses confirmatory factor analysis to test the factor structure of a
      modified version of the Fagerstrom Test for Nicotine Dependence (FTND) in an
      adolescent sample. Specifically, we test the fit of a two-factor model
      specification as well as a single-factor solution. This study uses methods that
      are appropriate to the categorical nature of the items making up the FTND and is
      the first study to examine the measurement properties of the FTND in a large
      adolescent sample. Both the two-factor and single-factor model specifications
      achieved acceptable model fit. It should be noted that these study results speak
      to the dimensionality of the FTND and not to the dimensionality of a general
      nicotine dependence construct in adolescents.

PMID- 16647217
TI  - Nicotine dependence subtypes: association with smoking history, diagnostic
      criteria and psychiatric disorders in 5440 regular smokers from the Vietnam Era
      Twin Registry.
AB  - Studies suggest empirically derived subtypes of nicotine dependence exist in
      young adult populations with short smoking careers. It is not known if classes of
      dependence exist in middle aged smokers with longer smoking careers and whether
      these classes reflect quantitative or qualitative differences. It is not known if
      psychiatric disorders are associated with classes of nicotine dependence.
      Nicotine dependence symptoms were obtained from a 1992 administration of the
      Diagnostic Interview Schedule. Latent Class Analyses (LCA) was computed using
      data from 5440 members of the Vietnam Era Twin Registry. LCA was used to derive
      significantly different classes of nicotine dependence, which were assessed for
      their association with smoking history, nicotine dependence, and other
      psychiatric disorders. The LCA model which best fit the data was a 4 class
      solution characterized by severity. Age onset of regular smoking decreased with
      more severe classes. Cigarette consumption, failed cessation and psychiatric
      disorders were associated with more severe classes. Empirically derived subtypes
      of nicotine dependence are mostly characterized by increasing severity.
      Suggestions for refinement of nicotine dependence diagnostic criteria are
      discussed.

PMID- 16647218
TI  - Family based association analysis of statistically derived quantitative traits
      for drug use in ADHD and the dopamine transporter gene.
AB  - OBJECTIVE: To determine whether SNPs within the dopamine transporter gene (DAT)
      are associated with quantitative phenotypes generated from drug frequency
      variables in an ADHD sample. METHOD: 35 SNPs were genotyped in and around DAT. We
      developed a quantitative phenotype at each SNP by weighting the drug frequency
      variables. The weights were selected to maximize the heritability at each SNP.
      Once a quantitative phenotype was generated at each SNP, a screening procedure
      was used to select and test the SNPs with the greatest power to detect an
      association in DAT. RESULTS: No SNPs in DAT were associated with the quantitative
      phenotypes generated from the drug frequency variables after the multiple
      comparisons adjustment; however, some SNPs achieved nominal significance. A
      sliding window of analysis of 3 SNPs also resulted in only nominal associations.
      CONCLUSIONS: SNPs in DAT do not appear to be associated with the phenotypes
      generated from drug frequency variables among individuals with ADHD.

PMID- 16647219
TI  - Application of item response theory to quantify substance use disorder severity.
AB  - OBJECTIVE: The present investigation had two main goals: (1) Determine whether
      binary substance use disorder (SUD) diagnoses are indicators of a unidimensional
      trait indexing severity of disorder; and, (2) demonstrate the predictive,
      concurrent and construct validity of the SUD severity scale. METHODS: Boys and
      their biological parents were administered structured diagnostic interviews to
      diagnose SUD. Item response theory (IRT) was applied to determine whether the
      diagnoses are indicators of a unidimensional trait. The score on this scale was
      correlated with substance use behavior, violence, treatment history, risky sex,
      and social adjustment. RESULTS: SUD diagnoses are indicators of a unidimensional
      latent trait. Maternal and paternal SUD severity predicted son's SUD severity at
      age 19. The score on the SUD severity scale correlated with drug use frequency,
      number of different drugs used in lifetime, treatment seeking, illegal behavior,
      social maladjustment, and risky sex. CONCLUSION: SUD can be quantified on an
      interval scale indexing severity of disorder. The advantages of measuring SUD
      severity as a continuous trait are discussed.

PMID- 16647220
TI  - Neurotransmitter depletion may be a cause of dementia pathology rather than an
      effect.
AB  - BACKGROUND: There is widespread loss of acetylcholine and other neurotransmitters
      in Alzheimer's disease and vascular dementia. It has generally been assumed that
      death of neurons causes neurotransmitter loss, but alternatively neurotransmitter
      depletion itself may at least contribute to neurodegeneration. PRESENTATION OF
      THE HYPOTHESIS: Transgenic mice and pigs with inducible 50% depletion of
      acetylcholine, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid
      (GABA) and corticotrophin releasing factor will reproduce Alzheimer's disease or
      vascular dementia neuropathology, and pharmacologically restoring
      neurotransmitters will attenuate neuronal injury. TESTING THE HYPOTHESIS: Through
      nuclear transfer cloning, transgenic mice and pigs would be created with
      transgenes on one X chromosome, so that transgenes would only be expressed in
      half of all cells in female animals. Transgenes would encode tetracycline
      inducible short hairpin RNA (shRNA) designed to form small interfering RNA
      (siRNA) to knock down neurotransmitter biosynthesis in late adulthood. Transgene
      expressing neurons could be readily identified in tissue sections with
      fluorescent reporter genes. Cholinesterase inhibitors, antidepressants,
      benzodiazepines and CRF would then be administered in an attempt to rescue
      degenerating neurons. IMPLICATIONS OF THE HYPOTHESIS: The mice and pigs could
      serve as an important new model for the pathogenesis of dementia, especially if
      pharmacologically restoring neurotransmitters rescues degenerating neurons. The
      animals may also be useful for as models for other disorders such as multi-system
      atrophy, Parkinson's disease, and depression.

PMID- 16647221
TI  - Proton beam radiotherapy for uveal melanoma: results of Curie Institut-Orsay
      proton therapy center (ICPO).
AB  - PURPOSE: This study reports the results of proton beam radiotherapy based on a
      retrospective series of patients treated for uveal melanoma at the Orsay Center.
      METHODS AND MATERIALS: Between September 1991 and September 2001, 1,406 patients
      with uveal melanoma were treated by proton beam radiotherapy. A total dose of 60
      cobalt Gray equivalent (CGE) was delivered in 4 fractions on 4 days. Survival
      rates were determined using Kaplan-Meier estimates. Prognostic factors were
      determined by multivariate analysis using the Cox model. RESULTS: The median
      follow-up was 73 months (range, 24-142 months). The 5-year overall survival and
      metastasis-free survival rates were 79% and 80.6%, respectively. The 5-year local
      control rate was 96%. The 5-year enucleation for complications rate was 7.7%.
      Independent prognostic factors for overall survival were age (p < 0.0001), gender
      (p < 0.0003), tumor site (p < 0.0001), tumor thickness (p = 0.02), tumor diameter
      (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.003). Independent
      prognostic factors for metastasis-free survival were age (p = 0.0042), retinal
      detachment (p = 0.01), tumor site (p < 0.0001), tumor volume (p < 0.0001), local
      recurrence (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.002).
      Independent prognostic factors for local control were tumor diameter (p = 0.003)
      and macular area receiving at least 30 CGE (p = 0.01). Independent prognostic
      factors for enucleation for complications were tumor thickness (p < 0.0001) and
      lens volume receiving at least 30 CGE (p = 0.0002). CONCLUSION: This
      retrospective study confirms that proton beam radiotherapy ensures an excellent
      local control rate. Further clinical studies are required to decrease the
      incidence of postirradiation ocular complications.

PMID- 16647222
TI  - Final toxicity results of a radiation-dose escalation study in patients with non
      small-cell lung cancer (NSCLC): predictors for radiation pneumonitis and
      fibrosis.
AB  - PURPOSE: We aimed to report the final toxicity results on a radiation-dose
      escalation trial designed to test a hypothesis that very high doses of radiation
      could be safely administered to patients with non-small-cell lung cancer (NSCLC)
      by quantifying the dose-volume toxicity relationship of the lung. METHODS AND
      MATERIALS: A total of 109 patients with unresectable or medically inoperable
      NSCLC were enrolled and treated with radiation-dose escalation (on the basis of
      predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by
      use of 3D conformal techniques. Eighty-four patients (77%) received more than 69
      Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow
      up was 110 months. RESULTS: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15
      (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate
      analyses showed them to be (1) not associated with the dose prescribed to the
      tumor, and (2) significantly (p<0.001) associated with lung-dosimetric parameters
      such as the mean lung dose (MLD), volume of lung that received at least 20 Gy
      (V20), and the normal-tissue complication probability (NTCP) of the lung. If
      cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have
      positive predictive values of 50% to 71% and negative predictive value of 85% to
      89%. CONCLUSIONS: With long-term follow-up for toxicity, we have demonstrated
      that much higher doses of radiation than are traditionally administered can be
      safely delivered to a majority of patients with NSCLC. Quantitative lung dose
      volume toxicity-based dose escalation can form the basis for individualized high
      dose radiation treatment to maximize the therapeutic ratio in these patients.

PMID- 16647223
TI  - Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive
      tract: analysis of 74 cases. A Rare Cancer Network study.
AB  - PURPOSE: To retrospectively analyze a series of mucosal melanoma of the upper
      aerodigestive tract to determine the prognostic factors and contribute to
      understanding the role of radiotherapy in the therapeutic strategy. METHODS AND
      MATERIALS: Seventy-four patients were analyzed. The most frequent locations were
      nasal and oral, in 31 patients (41.9%) and 12 patients (16.2%), respectively.
      Sixty-three patients (85.1%) were in Stage I, 5 (6.8%) in Stage II, and 6 (8.1%)
      in Stage III. Treatment consisted of surgery in 17 patients (23.0%), surgery and
      radiotherapy in 42 (56.8%), radiotherapy in 11 (14.9%), and chemo-immunotherapy
      in 4 (5.4%). Median follow-up was 20 months. RESULTS: Local control at 3 years
      was 57% after surgery alone and 71% after surgery and radiotherapy. Overall and
      disease-free survival rates, respectively, were 41% and 31% at 3 years and 14%
      and 22% at 10 years. After univariate analysis, female gender, melanosis, tumor
      size </=3 cm, Stage I, postoperative radiotherapy, and complete remission were
      favorable prognostic factors. Stage I and melanosis were confirmed by
      multivariate analysis. CONCLUSIONS: Local control was improved by postoperative
      radiotherapy, despite survival being as poor as in other published series. Stage
      I and melanosis at diagnosis were the most favorable prognostic factors.

PMID- 16647224
TI  - Preventive effect of oral administration of 6-(methylsulfinyl)hexyl
      isothiocyanate derived from wasabi (Wasabia japonica Matsum) against pulmonary
      metastasis of B16-BL6 mouse melanoma cells.
AB  - AIM: Effect of oral administration of 6-(methylsulfinyl)hexyl isothiocyanate (6
      MITC) or a 6-MITC-containing T-wasabi fraction from wasabi root (Wasabia japonica
      Matsum) to inhibit the macroscopic pulmonary metastasis was studied with a murine
      B16-BL6 melanoma model. METHOD: Two administration routes, subcutaneous or
      intravenous, and two administration times, prior to or concomitant with tumor
      inoculation, of 6-MITC or T-wasabi against the metastatic foci formation in
      C57BL/6J mouse lungs were compared. RESULTS: The number of metastasized foci per
      lung in either subcutaneous or intravenous injection was significantly reduced by
      intake of 6-MITC or a T-wasabi fraction. The maximum reduction by a T-wasabi
      fraction reached to 82%. Fifty-six percent of foci formation was inhibited by a 2
      week-prior administration of 6-MITC (200 microM), whereas only 27% inhibition was
      obtained by a concomitant administration with tumor inoculation. Neither 6-MITC
      nor T-wasabi at tested concentrations showed any toxic effects. DISCUSSION:
      Together with our previous results, a component of the Japanese pungent spice,
      wasabi appears to inhibit not only tumor cell growth but also tumor metastasis.
      Therefore, 6-MITC from wasabi is apparently a useful dietary candidate for
      controlling tumor progression.

PMID- 16647225
TI  - Real-time detection of mesothelin in pancreatic cancer cell line supernatant
      using an acoustic wave immunosensor.
AB  - BACKGROUND: An acoustic wave immunosensor was developed to illustrate the
      viability of such devices in early detection of molecular cancer biomarkers. The
      methods described here involve a real-time, less invasive technique for detecting
      mesothelin, a protein that has been linked to pancreatic and ovarian cancer.
      METHODS: Antibodies were immobilized on the gold surface of the device via a self
      assembled alkanethiol monolayer. Supernatant from two different pancreatic cancer
      cell-lines (PL1 and CAPAN2) containing an unknown concentration of mesothelin was
      tested for the protein by a flow-through analytical technique in three types of
      experiments. Binding of the mesothelin to the immobilized antibody layer caused a
      shift in the device's resonant frequency, which was correlated to the
      concentration of supernatant. A reference sensor was used to correct for
      frequency shifts caused by pressure or viscosity effects from the injection of
      the supernatant solution. RESULTS: Repeated experiments indicate that the sensors
      are capable of nanogram detection thresholds of mesothelin proteins at room
      temperature and in complex mixture. CONCLUSIONS: Acoustic wave device biosensors
      have the potential to become a valuable tool in screening for pancreatic as well
      as other types of cancers. The main features include real-time detection, high
      sensitivity, and ease of use.

PMID- 16647226
TI  - Case-control study of oropharyngeal cancer.
AB  - BACKGROUND: In order to test some hypotheses of risk factors for oropharyngeal
      cancer (neoplasm of base of tongue, palate and tonsils) matched case-control
      study was conducted in Belgrade, Serbia and Montenegro, during the period 1998
      2000. METHODS: Study comprised 100 incidence cases with oropharyngeal cancer and
      100 controls with some non-malignant diseases of head and neck. RESULTS:
      According to multivariate analysis, ever smoking, interaction between smoking and
      alcohol consumption, and occupational exposure to wood dust were found to be
      independent risk factors for oropharyngeal cancer (odds ratio-OR=5.10 95%
      confidence intervals-95% CI=1.70-15.27, OR=2.61 95% CI=1.54-4.41, and OR=4.16 95%
      CI=1.45-11.91, respectively). CONCLUSION: The results of the present study are in
      line with other authors' findings showing that smoking and alcohol consumption
      are the main risk factors for oropharyngeal cancer. The effect of occupational
      exposure to wood dust warrants further investigation.

PMID- 16647227
TI  - Salmonella enterica serovar Enteritidis colonization of the chicken caecum
      requires the HilA regulatory protein.
AB  - Invasion of Salmonella into intestinal epithelial cells is believed to be
      essential for the pathogenesis of Salmonella infections. Invasion is mediated by
      genes located on the Salmonella pathogenicity Island I (SPI-1), which are needed
      for assembling a type three secretion system, that mediates injection of
      bacterial proteins into the cytosol of epithelial cells, resulting in
      cytoskeletal rearrangements and as a consequence invasion. HilA is the key
      regulator of the Salmonella Pathogenicity Island I. To assess the role of hilA in
      colonization of gut and internal organs in poultry, animals were infected with
      10(8) CFU of a delta hilA mutant of S. Enteritidis and its parent strain at day
      of hatch. Very low numbers of delta hilA mutant strain were able to colonize the
      internal organs shortly after infection, but they were not eliminated from
      internal organs at 4 weeks post-infection. At that time, the colonization level
      of the wild type bacteria in internal organs was decreased to the same low level
      compared with delta hilA mutant strain bacteria. Shedding of the delta hilA
      mutant strain and colonization of the caeca was seriously decreased relative to
      the parent strain starting from Day 5 post-infection. At 4 weeks post-infection,
      the delta hilA mutant strain was more or less eliminated from the chicken gut,
      while the parent strain was still shed to a high level and colonized the caeca to
      a high extent (more than 10(7) CFU/g). It is concluded that hilA is involved in
      long-term shedding and colonization of S. Enteritidis in the chicken caeca.

PMID- 16647228
TI  - In vitro modulation of HERG channels by organochlorine solvent trichlormethane as
      potential explanation for proarrhythmic effects of chloroform.
AB  - Acute chloroform intoxication can cause depression of the central nervous system
      and may lead to death from lethal arrhythmias or respiratory arrest. Thus, the
      organic solvent is no longer in clinical use as an anaesthetic, but still plays a
      role in cases of suicide, homicide or inhalation for psychotropic effects.
      Several cases of lethal arrhythmia after intoxication with chloroform have been
      described. Pharmacological inhibition of cardiac "human ether-a-go-go-related
      gene" (HERG) potassium channels is linked to proarrhythmic effects of cardiac and
      noncardiac drugs. To further investigate the electrophysiological basis of the
      arrhythmogenic potential of chloroform, we analysed inhibitory effects of
      chloroform on cloned HERG potassium channels, heterologously expressed in Xenopus
      oocytes and in Human Embryonic Kidney (HEK 293) cells using the double-electrode
      voltage-clamp technique and the whole-cell patch-clamp technique, respectively.
      In HEK cells, chloroform blocked HERG tail currents with an IC(50) of 4.97mM.
      Biophysical properties were further investigated in the Xenopus oocyte expression
      system. Onset and wash-out of block was fast and inhibition was completely
      reversible. Chloroform did not alter channel activation, however, direct channel
      inactivation was accelerated significantly. Steady-state-inactivation of HERG was
      not affected. Chloroform dependent block of HERG channels was voltage dependent
      with a decrease of inhibition at more positive membrane potentials. No frequency
      dependence of block could be observed. In summary, chloroform blocked HERG
      potassium channels probably in a toxicologically relevant concentration. These
      findings contribute to the pathophysiology of proarrhythmic effects in acute
      chloroform intoxication.

PMID- 16647229
TI  - Spermatogenesis in white-lipped peccaries (Tayassu pecari).
AB  - We describe here morphological and functional analyses of the spermatogenic
      process in sexually mature white-lipped peccaries. Ten sexually mature male
      animals, weighing approximately 39 kg were studied. Characteristics investigated
      included the gonadosomatic index (GSI), relative frequency of stages of the cycle
      of seminiferous epithelium (CSE), cell populations present in the seminiferous
      epithelium in stage 1 of CSE, intrinsic rate of spermatogenesis, Sertoli cell
      index, height of seminiferous epithelium and diameter of seminiferous tubules,
      volumetric proportion of components of the testicular parenchyma and length of
      seminiferous tubules per testis and per gram of testis. The GSI was 0.19%,
      relative frequencies of pre-meiotic, meiotic and post-meiotic phases were,
      respectively 43.6%, 13.8% and 42.6%, general rate of spermatogenesis was 25.8,
      each Sertoli cell supported an average 18.4 germinative cells, height of
      seminiferous epithelium and diameter of seminiferous tubules were, respectively,
      78.4 microm and 225.6 microm, testicular parenchyma was composed by 75.8%
      seminiferous tubules and 24.2% intertubular tissue, and length of seminiferous
      tubules per gram of testis was 15.8m. These results show that, except for overall
      rate of spermatogenesis, the spermatogenic process in white-lipped peccaries is
      very similar to that of collared peccaries, and that Sertoli cells have a greater
      capacity to support germinative cells than most domestic mammals.

PMID- 16647230
TI  - Preparation of roxithromycin-polymeric microspheres by the emulsion solvent
      diffusion method for taste masking.
AB  - Microspheres of roxithromycin with Eudragit S100 and silica were prepared by the
      emulsion solvent diffusion method to mask the bitter taste of the antibiotic. The
      effect of different polymers and drug-polymer ratios on the taste masking and the
      characteristics of the microspheres were investigated. It was found that Eudragit
      S100 was the best for masking the unpleasant taste of roxithromycin among the six
      kinds of polymers investigated. The results of DSC, X-ray diffraction and IR
      showed that there were several combinations of roxithromycin and Eudragit S100.
      The influence of other formulation factors, i.e. dichloromethane-acetone ratios
      and silica-polymer ratios on the properties of the microspheres were also
      examined. In conclusion, the results of the present study will be helpful for the
      preparation of oral forms of roxithromycin with an acceptable taste.

PMID- 16647231
TI  - Local controlled drug delivery to the brain: mathematical modeling of the
      underlying mass transport mechanisms.
AB  - The mass transport mechanisms involved in the controlled delivery of drugs to
      living brain tissue are complex and yet not fully understood. Often the drug is
      embedded within a polymeric or lipidic matrix, which is directly administered
      into the brain tissue, that is, intracranially. Different types of systems,
      including microparticles and disc- or rod-shaped implants are used to control the
      release rate and, thus, to optimize the drug concentrations at the site of action
      in the brain over prolonged periods of time. Most of these dosage forms are
      biodegradable to avoid the need for the removal of empty remnants after drug
      exhaustion. Various physical and chemical processes are involved in the control
      of drug release from these systems, including water penetration, drug
      dissolution, degradation of the matrix and drug diffusion. Once the drug has been
      released from the delivery system, it has to be transported through the living
      brain tissue to the target site(s). Again, a variety of phenomena, including
      diffusion, drug metabolism and degradation, passive or active uptake into CNS
      tissue and convection can be of importance for the fate of the drug. An overview
      is given of the current knowledge of the nature of barriers to free access of
      drug to tumour sites within the brain and the state of the art of: (i)
      mathematical modeling approaches describing the physical transport processes and
      chemical reactions which can occur in different types of intracranially
      administered drug delivery systems, and of (ii) theories quantifying the mass
      transport phenomena occurring after drug release in the living tissue. Both,
      simplified as well as complex mathematical models are presented and their major
      advantages and shortcomings discussed. Interestingly, there is a significant lack
      of mechanistically realistic, comprehensive theories describing both parts in
      detail, namely, drug transport in the dosage form and in the living brain tissue.
      High quality experimental data on drug concentrations in the brain tissue are
      difficult to obtain, hence this is itself an issue in testing mathematical
      approaches. As a future perspective, the potential benefits and limitations of
      these mathematical theories aiming to facilitate the design of advanced
      intracranial drug delivery systems and to improve the efficiency of the
      respective pharmacotherapies are discussed.

PMID- 16647232
TI  - Enhancement of the dissolution rate and oral absorption of a poorly water soluble
      drug by formation of surfactant-containing microparticles.
AB  - The slow dissolution rate exhibited by poorly water-soluble drugs is a major
      challenge in the drug development process. Following oral administration, drugs
      with slow dissolution rates generally show erratic and incomplete absorption
      which may lead to therapeutic failure. The aim of this study was to improve the
      dissolution rate and subsequently the oral absorption and bioavailability of a
      model poorly water-soluble drug. Microparticles containing the model drug
      (griseofulvin) were produced by spray drying the drug in the absence/presence of
      a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant
      to improve the particle wetting and hence the dissolution rate. The spray dried
      particles were characterized and in vitro dissolution studies and in vivo
      absorption studies were carried out. The results obtained showed that the
      dissolution rate and absolute oral bioavailability of the spray dried
      griseofulvin/Poloxamer 407 particles were significantly increased compared to the
      control. Although spray drying griseofulvin alone increased the drug's in vitro
      dissolution rate, no significant improvement was seen in the absolute oral
      bioavailability when compared to the control. Therefore, it is believed that the
      better wetting characteristics conferred by the hydrophilic surfactant was
      responsible for the enhanced dissolution rate and absolute oral bioavailability
      of the model drug.

PMID- 16647233
TI  - Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic
      treatment in Wistar rats.
AB  - Achillea millefolium L. (Asteraceae), popularly known as yarrow, has been used in
      folk medicine to treat complaints such as inflammation, pain, wounds, hemorrhages
      and gastrointestinal disturbances. The aim of the present study was to assess the
      safety and efficacy of the aqueous extract (AE) of the plant after chronic
      exposure. Indeed, the AE was effective in protecting the gastric mucosa against
      acute gastric lesions induced by ethanol and indomethacin and in healing chronic
      gastric lesions induced by acetic acid with (ED(50)=32 mg/kg, p.o.). Safety
      studies were performed in female and male Wistar rats treated daily with AE (0.3
      1.2 g/kg, p.o./day) or vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive
      days. Satellite groups consisted of animals sacrificed 30 days after the end of
      these treatments. Clinical observations, body and organ weight measurements,
      gross autopsy, hematology, clinical biochemical and histopathological
      examinations were performed. Slight changes in liver weight, cholesterol, HDL
      cholesterol and glucose were observed in male and female animals. These changes
      were not correlated with dose or time of exposure of the animals to the AE.
      Overall, the results show the antiulcer potential of the aerial parts of the
      Achillea millefolium which is accompanied by no signs of relevant toxicity even
      at very long chronic exposure.

PMID- 16647234
TI  - Analgesic activity of some Indian medicinal plants.
AB  - In the present study of some of the Indian medicinal plants Sida acuta whole
      plant (Malvaeae), Stylosanthes fruticosa (whole plant) (Papilionaceae), Toona
      ciliata (heart wood) (Meliaceao), Bougainvilla spectabilis (leaves)
      (Nyctaginaceae), Ficus glomerata (bark, leaves) (Moraceae) and Polyalthia
      longifolia (leaves) (Annonaceae). The different plants were used in folklore
      medicine in the treatment of toothache and strengthening of gums, anthelmintic,
      kidney diseases, analgesic, anti-inflammatory, hepatoprotective,
      antihyperglycaemic, antihyperglycaemic and anticancer. The extract was prepared
      using powdered material with ethanol, concentrated under vacuo and were evaluated
      for analgesic activity by analgesiometer at three dose level (100, 300 and
      500mg/kg). Analgesic activity was significant with Toona ciliata (heart wood)
      ethanolic extract when compared with other extracts and its activity was
      confirmed by tail immersion method.

PMID- 16647235
TI  - Antinociceptive and antidepressant like effects of Securidaca longepedunculata
      root extract in mice.
AB  - The aqueous root extract of Securidaca longepedunculata (polygalaceae) was
      investigated for possible antinociceptive and central nervous system (CNS)
      effects in mice. Three nociceptive models; acetic acid, formalin and tail-flick
      tests were used to study the antinociceptive activity. Rectal temperature test
      was employed as an adjunct to the nociceptive models. The extract at 200 and 400
      mg/kg significantly and dose dependently reduced the nociception induced by the
      acetic acid and in the early phase of formalin test (P<0.05). The extract exerted
      significant (P<0.05) hypothermic effect in the 15 and 30 min of the rectal
      temperature test. The antinociceptive and hypothermic effects were partially
      reversed by naloxone (1mg/kg). The tail-flick test produced an insignificant
      increase in tail-flick latency at 400 mg/kg after 60 min of the test, but
      significantly (P<0.05) increase tail-flick latency in the 400mg/kg group of
      animals pre-treated with naloxone (1 mg/kg) after 120 min of the test. The
      extract also produced a significant (P<0.05) naloxone reversible antidepressant
      like effect in the forced swimming test (an animal model of depression).
      Collectively, these results suggest that the extract possess antinociceptive and
      antidepressant like effects with possible involvement of opioidergic pathways.
      The extract at limit dose of 2 g/kg body weight appeared to be safe in oral
      formulation.

PMID- 16647236
TI  - The development of visual- and auditory processing in Rett syndrome: an ERP
      study.
AB  - Rett syndrome is a neurodevelopmental disorder that occurs almost exclusively in
      females. It is characterized by a progressive loss of intellectual functioning
      and motor skills, and the development of stereotypic hand movements, that occur
      after a period of normal development. Event-related potentials were recorded to a
      passive auditory- and visual oddball task in 17 females with Rett syndrome aged
      between 2 and 60 years, and age-matched controls. Overall the participants with
      Rett syndrome had longer ERP latencies and smaller ERP amplitudes than the
      Control group suggesting slowed information processing and reduced brain
      activation. The Rett groups also failed to show typical developmental changes in
      event-related brain activity and revealed a marked decline in ERP task modulation
      with increasing age.

PMID- 16647237
TI  - Micellar liquid chromatographic determination of five antianginals in
      pharmaceuticals.
AB  - A procedure was developed for the determination of five antianginals (diltiazem,
      nadolol, nifedipine, propranolol and verapamil), using hybrid micellar mobile
      phases of sodium dodecyl sulphate (SDS) and pentanol, a C18 column and UV
      detection. All possible combinations of antianginals were resolved and determined
      using a mobile phase of 0.05 M SDS-5% pentanol with an analysis time of 9 min.
      Repeatabilities and intermediate precision were evaluated at four different drug
      concentrations in the 2-20 microg/ml (n=5) range. Limits of detection were in the
      range 0.028 microg/ml for diltiazem and 0.130 microg/ml for verapamil. The range
      of the limit of quantitation was from 0.092 to 0.431 microg/ml for the same
      compounds. Antianginal drugs were studied in pharmaceuticals with no interference
      from related compounds. The results of the analyses of pharmaceuticals
      formulations were in agreement with the declared compositions.

PMID- 16647238
TI  - Fuzzy role of hyperhomocysteinemia in hemodialysis patients' mortality.
AB  - Recent studies give contradictory data regarding the role of hyperhomocysteinemia
      (hyperHcy) in cardiovascular (CV) morbidity and mortality in hemodialysis (HD)
      patients. The aims of the present study were to detect the most powerful
      variables associated with hyperHcy as well as to evaluate the relationship
      between hyperHcy and CV morbidity and mortality. The prospective follow-up study
      of 113 patients (52 males, aged 55.2+/-13.1 years) maintained by HD for 81.9+/
      56.9 months at our Institute was carried out over 55 months. Fifty-seven (50.4%)
      of the examined patients were supplemented with water-soluble vitamins including
      folic acid and vitamin B complex pills or ampoules. Total serum Hcy level was
      determined by high-performance liquid chromatography, while serum folic acid and
      vitamin B(12) were measured by radioimmunoassay. The multivariate analysis showed
      HD duration (r=0.608; P=0.02) and folic acid serum level (r=-0.580; P=0.03) to be
      significant predictors of serum tHcy concentration. The multivariate Cox
      regression analysis of CV mortality revealed diabetes mellitus and heart failure
      as the most powerful positive predictors, while creatinine, albumin and vitamins
      intake therapy were negative predictors of CV mortality. Long-term
      supplementation with the usual doses of vitamins is followed with increased
      survival in hemodialysis patients. Although total serum Hcy level was not found
      to be a predictor of overall and CV mortality, the role of hyperHcy. as risk
      factor for CVD cannot be excluded in hemodialysis patients.

PMID- 16647239
TI  - The effect of dendritic cells activated by OK-432 and pulsed with antigens on
      cytokine induced killers.
AB  - AIM: To study the effect of OK-432 on the maturation and function of human
      peripheral blood monocyte-derived dendritic cells, and the effect of these
      dendritic cells on the proliferation and anti-tumor function of cytokine induced
      killers. METHODS: Through the analysis of DCs' surface molecules, the detection
      of the proliferation and anti-tumor function of CIKs activated by DCs, we
      researched the influence of OK-432 on DCs and CIKs. RESULTS: OK-432 have the
      potential of promoting DCs to express CD1a, CD80, CD83, HLA-DR highly, which is
      stronger than LPS; DCs activated by OK-432 can facilitate the proliferation and
      function of CIKs. CONCLUSION: OK-432 can induce DCs' maturation and can thus
      promote CIKs' functions.

PMID- 16647240
TI  - Naltrexone renders one-session exposure therapy less effective: a controlled
      pilot study.
AB  - In vivo exposure has become the gold standard treatment for specific phobia. The
      endogenous opioid system is one mechanism proposed to explain why exposure
      provides such quick and effective treatment for specific phobia. The effect of
      naltrexone on fear and avoidance behavior was investigated among 15 specific
      phobia participants who received exposure treatment. Participants were randomly
      assigned to receive naltrexone, placebo, or no drug prior to attending one
      session exposure treatment. Mixed effects regression results revealed that across
      time, the naltrexone group tolerated significantly less time in the room with the
      feared animal (Behavioral Avoidance Index) as compared to the placebo and no drug
      groups. Phobic individuals assigned to the naltrexone group had significantly
      higher fear ratings across time in comparison to the placebo group. Results
      provide support for the endogenous opioid system as a potential underlying
      biological mechanism associated with behavioral changes during in vivo exposure.

PMID- 16647241
TI  - Are responsibility beliefs inflated in non-checking OCD patients?
AB  - Cognitive models of obsessive-compulsive disorder [e.g., Salkovskis, P. M.
      (1999). Understanding and treating obsessive-compulsive disorder. Behaviour
      Research and Therapy, 37(Suppl. 1), S29-S52] propose a key role for inflated
      responsibility for harm. Studies evaluating such beliefs typically use
      heterogeneous samples including several OCD subtypes. A recent investigation by
      Foa et al. [Foa, E. B., Sacks, M. B., Tolin, D. F., Prezworski, A., & Amir, N.
      (2002). Inflated perception of responsibility for harm in OCD patients with and
      without checking compulsions: a replication and extension. Journal of Anxiety
      Disorders, 16(4), 443-453] found responsibility to be elevated in OC checkers,
      but not in non-checking OCD patients, relative to non-anxious controls. In that
      study, the responsibility measure included checking scenarios, thus leaving the
      possibility that these findings may have been due to criterion contamination. The
      present study investigated responsibility beliefs in OC checkers (n=39) and non
      checkers (n=20), anxious controls (n=22), and non-clinical controls (n=69), using
      measures of responsibility which do not have item overlap with OCD symptoms.
      Results indicated that both OC groups showed greater responsibility beliefs
      relative to anxious and non-anxious controls. OC checkers endorsed greater
      responsibility appraisals than anxious and non-clinical control groups. In
      contrast, non-checking OCs reported greater responsibility appraisals than non
      clinical controls, but did not differ from anxious controls and OC checkers.
      Results are discussed in the context of the cognitive model of OCD.

PMID- 16647242
TI  - Cerebrospinal fluid IL-6, HSP72, and TNF-alpha in exercising humans.
AB  - During exercise the concentration of interleukin (IL)-6 and of heat shock protein
      (HSP) 72 increases in plasma, especially in fasting subjects. Both IL-6 and HSP72
      are involved in a variety of metabolic and immunological processes, including
      some within the central nervous system and, accordingly, they are present not
      only in plasma but also in the cerebrospinal fluid (CSF). To evaluate whether,
      the two pools equilibrate we determined the levels of IL-6 and HSP72 in CSF, at a
      time when their plasma levels were increased due to exercise. Measurements of TNF
      alpha served as a control, as its plasma level remains stable during exercise.
      Two groups of healthy, fit males performed 2 h of strenuous exercise with either
      carbohydrate ingestion (n=8) or placebo (n=8). The concentration of IL-6, HSP72,
      and TNF-alpha was measured in arterial blood and in the CSF obtained by a lumbar
      puncture immediately after exercise. A third group of subjects served as resting
      controls (n=8). At rest, CSF levels of IL-6 and HSP72 were 2- and 3-fold higher
      than the plasma levels, respectively (P<.05). During exercise, with and without
      carbohydrate ingestion, plasma IL-6 increased 8- and 18-fold, respectively, and
      HSP72 increased 5-fold (P<.05). However, the concentrations of IL-6 and HSP72 in
      CSF did not change with exercise and were therefore below their corresponding
      plasma levels. The concentration of TNF-alpha in CSF was below that in plasma and
      both remained stable during exercise. The findings that resting CSF levels of IL
      6 and HSP72 are higher than in plasma and that they remain stable despite
      exercise-induced, profound increases in their systemic levels, suggest that the
      CSF pool is segregated from that in blood.

PMID- 16647243
TI  - Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS
      pro-inflammatory cytokine responses.
AB  - Prior exposure to a stressor can potentiate CNS pro-inflammatory immune responses
      to a peripheral immune challenge. However, the neuroimmune substrate(s) mediating
      this effect has not been determined. The present investigation examined whether
      microglia serve as this neuroimmune substrate given that microglia are the
      primary immune effector cell in the CNS. The effect of inescapable shock (IS) on
      glial activation (MHC II, CD11b, Iba-1, and GFAP) and regulatory markers (CD200)
      in vivo, and microglia pro-inflammatory responses (interleukin-1beta; IL-1beta)
      to lipopolysaccharide (LPS) ex vivo, were assessed in rat hippocampus. IS
      upregulated the microglia activation marker MHC II 24h post-IS, while the
      astroglia marker GFAP was unaffected. IS also downregulated the neuronal
      glycoprotein CD200, which functions to hold microglia in a quiescent state.
      Moreover, IS potentiated the pro-inflammatory response to LPS ex vivo 24h post-IS
      in isolated hippocampal microglia. Finally, the behavioral controllability of
      shock was manipulated and the effect of escapable (controllable) shock was
      comparable to the effect of IS on hippocampal microglia responses to LPS ex vivo.
      The present results suggest that stress can activate microglia, thereby
      sensitizing the pro-inflammatory reactivity of microglia to immunogenic stimuli.

PMID- 16647244
TI  - Immunity and emotions: lipopolysaccharide increases defensive behaviours and
      potentiates despair in mice.
AB  - Many studies have pointed out the relationships between immunity and depression,
      supporting a neuroimmune hypothesis of depressive disorders. However, despite the
      growing interest for such a hypothesis and the amount of clinical and
      experimental data available, the precise nature of this relationship between
      immunity and depression remains unclear. The present study aimed to investigate
      further the link between depression and immunity in mice using the modified
      version of the forced-swimming test. Based on a two-session test, results from
      our first experiment showed that endotoxin enhanced active defensive behaviours
      in mice during the first exposure to water, but was associated with increased
      immobility (i.e., 'behavioural despair') in the subsequent session. In our second
      experiment, we showed that these effects were blocked by a chronic antidepressant
      treatment with imipramine. Finally, we suggest a link between immunity and
      depression, based on the behavioural context in which immune activation takes
      place. We hypothesize that immune activation, by enhancing reactivity to the
      negative features of a given situation, increases defensive motivation of
      subjects, but therefore makes them more vulnerable to the deleterious emotional
      consequences of failure in defensive strategies.

PMID- 16647245
TI  - Inflammation and the pathophysiology of work-related musculoskeletal disorders.
AB  - Work-related musculoskeletal disorders (MSDs) have accounted for a significant
      proportion of work injuries and workers' compensation claims in industrialized
      nations since the late 1980s. Despite epidemiological evidence for the role of
      repetition and force in the onset and progression of work-related MSDs, complete
      understanding of these important occupational health problems requires further
      elucidation of pathophysiological mechanisms of the tissue response, particularly
      in the early stage of these disorders. Results from several clinical and
      experimental studies indicate that tissue microtraumas occur as a consequence of
      performing repetitive and/or forceful tasks, and that this mechanical tissue
      injury leads to local and perhaps even systemic inflammation, followed by
      fibrotic and structural tissue changes. Here we review work linking inflammation
      and the development of work-related MSDs. We also propose a conceptual framework
      suggesting the potential roles that inflammation may play in these disorders, and
      how inflammation may contribute to pain, motor dysfunction, and to puzzling
      psychological symptoms that are often characteristic of patients with work
      related MSDs.

PMID- 16647246
TI  - The effects of a specific speech and language training program on students of a
      radio announcing course.
AB  - The purpose of this study was to determine whether individuals show differences
      in speech and voice during reading of the same news before and after attending a
      radio announcing course. Twenty-five students of a Radio Announcing Course in Sao
      Paulo city, 17 men and 8 women, aged 19 to 55 years, participated in this study.
      The readings were recorded in a professional audio studio, and the speech samples
      were submitted to perceptual and acoustic analysis. For the perceptual analysis,
      the samples were randomly presented in pairs and five trained speech pathologists
      identified each recording as pre- and posttraining, and also justified their
      choices by indicating what parameters better based their judgment: type of voice,
      articulation and pronunciation, loudness, pitch, resonance, speech rate,
      respiratory coordination, and use of emphasis. The acoustic parameters analyzed
      were mean, minimum, and maximum fundamental frequency, frequency range, text
      duration, and pause duration. The perceptual analysis showed that the
      posttraining speech samples were considered the best productions in 80% of the
      evaluations. Emphasis characterized the readings (70.4%), followed by type of
      voice (44.8%) and pitch (40.8%). Acoustic analysis showed higher mean fundamental
      frequency and increase of frequency range posttraining. These results indicated
      richer modulation in the posttraining readings. There are differences in the
      readings of the same news pre- and posttraining in a radio announcing course, and
      the posttraining reading was considered the best production, indicating the
      positive effect of the training.

PMID- 16647247
TI  - Acoustical correlates of affective prosody.
AB  - The word "Anna" was spoken by 12 female and 11 male subjects with six different
      emotional expressions: "rage/hot anger," "despair/lamentation,"
      "contempt/disgust," "joyful surprise," "voluptuous enjoyment/sensual
      satisfaction," and "affection/tenderness." In an acoustical analysis, 94
      parameters were extracted from the speech samples and broken down by correlation
      analysis to 15 parameters entering subsequent statistical tests. The results show
      that each emotion can be characterized by a specific acoustic profile,
      differentiating that emotion significantly from all others. If aversive emotions
      are tested against hedonistic emotions as a group, it turns out that the best
      indicator of aversiveness is the ratio of peak frequency (frequency with the
      highest amplitude) to fundamental frequency, followed by the peak frequency, the
      percentage of time segments with nonharmonic structure ("noise"), frequency range
      within single time segments, and time of the maximum of the peak frequency within
      the utterance. Only the last parameter, however, codes aversiveness independent
      of the loudness of an utterance.

PMID- 16647248
TI  - Candidaemia in Europe: epidemiology and resistance.
AB  - Despite the widespread use of antifungals for prophylaxis, Candida bloodstream
      infection (BSI) remains the most frequent life-threatening fungal disease. From
      an analysis of multi-institutional surveys of Candida BSIs performed in Europe,
      including the large prospective survey by the European Confederation of Medical
      Mycology (2089 episodes from seven countries), a limited role of species with
      decreased susceptibility to azoles in causing BSIs and a low proportion of
      antifungal resistance was evident. Large prospective epidemiological surveys
      using common databases are needed to monitor trends in incidence and changes in
      species distribution, to identify new at-risk patients and to evaluate the impact
      of the introduction into the market of new antifungal agents.

PMID- 16647249
TI  - Homocysteine levels in adolescent schizophrenia patients.
AB  - Homocysteine is a sulfur containing amino acid that has been widely investigated
      for its putative role in cardiovascular and neuropsychiatric disorders. It has
      been suggested that homocysteine has implications especially in young, male
      schizophrenia patients. In this prospective case-control study, we compared
      plasma homocysteine levels in a group of adolescent schizophrenia inpatients
      (aged 14-21 years; n=23) to normal healthy controls (n=51). Mean plasma
      homocysteine levels were significantly higher in the patient group than in the
      control group (15.40+/-2.00 and 9.78+/-0.33 micromol/L, respectively, p<0.032).
      The difference was almost entirely attributable to the male schizophrenia
      subgroup (18.18+/-5.65 in male patients vs. 10.31+/-5.33 micromol/L in female
      patients). The group x sex interaction was statistically significant (p=0.0035).
      These data indicate that a subgroup of male adolescent schizophrenia patients has
      high homocysteine blood levels. The role of homocysteine in the pathophysiology
      of adolescent-onset schizophrenia merits further investigation.

PMID- 16647250
TI  - Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in
      Huntington's disease mice.
AB  - There is substantial evidence that a bioenergetic defect may play a role in the
      pathogenesis of Huntington's Disease (HD). A potential therapy for remediating
      defective energy metabolism is the mitochondrial cofactor, coenzyme Q10 (CoQ10).
      We have reported that CoQ10 is neuroprotective in the R6/2 transgenic mouse model
      of HD. Based upon the encouraging results of the CARE-HD trial and recent
      evidence that high-dose CoQ10 slows the progressive functional decline in
      Parkinson's disease, we performed a dose ranging study administering high levels
      of CoQ10 from two commercial sources in R6/2 mice to determine enhanced efficacy.
      High dose CoQ10 significantly extended survival in R6/2 mice, the degree of which
      was dose- and source-dependent. CoQ10 resulted in a marked improvement in motor
      performance and grip strength, with a reduction in weight loss, brain atrophy,
      and huntingtin inclusions in treated R6/2 mice. Brain levels of CoQ10 and CoQ9
      were significantly lower in R6/2 mice, in comparison to wild type littermate
      control mice. Oral administration of CoQ10 elevated CoQ10 plasma levels and
      significantly increased brain levels of CoQ9, CoQ10, and ATP in R6/2 mice, while
      reducing 8-hydroxy-2-deoxyguanosine concentrations, a marker of oxidative damage.
      We demonstrate that high-dose administration of CoQ10 exerts a greater
      therapeutic benefit in a dose dependent manner in R6/2 mice than previously
      reported and suggest that clinical trials using high dose CoQ10 in HD patients
      are warranted.

PMID- 16647251
TI  - [Left segmental omental infarction in a child: conservative treatment].
AB  - Omental infarction is a rare cause of acute abdomen that usually occurs on the
      right side. Left omental ischemia is rare in adults and to our knowledge not yet
      described in children. Its diagnosis, although difficult, is important because it
      can avoid surgery. We report a case of left segmental omental infarction in an 11
      year-old child, diagnosed by imaging studies, treated conservatively, and
      followed up by ultrasound until complete disappearance of the lesion.

PMID- 16647252
TI  - A characteristic pharmacological action of 'Yang-invigorating' Chinese tonifying
      herbs: enhancement of myocardial ATP-generation capacity.
AB  - In order to investigate the pharmacological basis of 'Yang-invigorating' action,
      the effect of oral treatment with the methanolic extract of 'Yang-invigorating'
      herbs on ATP-generation capacity was examined, using heart homogenates prepared
      from herb-pretreated mice. Tonifying (i.e., health-promoting) herbs of other
      functional categories were also included for comparison. The results indicated
      that 'Yang-invigorating' Chinese tonifying herbs could invariably enhance
      myocardial ATP-generation capacity, with the extent of stimulation varying among
      the herbs. In contrast, 'Yin-nourishing' herbs either did not stimulate or even
      decreased myocardial ATP-generation capacity. While 'Qi-invigorating' herbs
      produced variable effects on myocardial ATP-generation capacity, most of the
      'blood-enriching' herbs did not cause any significant changes. The results
      obtained from studies using myocardial mitochondrial fractions isolated from herb
      pretreated mice suggest that 'Yang-invigorating' herbs might speed up ATP
      generation by increasing mitochondrial electron transport. The ensemble of
      results has provided evidence for the first time to support the pharmacological
      basis of 'Yang invigoration' in Chinese medicine.

PMID- 16647253
TI  - Differential modulation of cell cycle, apoptosis and PPARgamma2 gene expression
      by PPARgamma agonists ciglitazone and 9-hydroxyoctadecadienoic acid in monocytic
      cells.
AB  - We sought to compare the effects of the thiazolidinedione ciglitazone with the
      endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9
      and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell
      proliferation and all three agonists increased cellular content of C18:0 fatty
      acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S
      phase and ciglitazone reduced the percentage of cells in G2/M phase of cell
      cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the
      fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937
      cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE
      was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic
      (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13
      HODE, possess differential, ligand specific actions in monocytic cells to
      regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.

PMID- 16647254
TI  - The transcriptional regulatory code of eukaryotic cells--insights from genome
      wide analysis of chromatin organization and transcription factor binding.
AB  - Control of eukaryotic gene expression involves combinatorial interactions between
      transcription factors and regulatory sequences in the genome. In addition,
      chromatin structure and modification states play key roles in determining the
      competence of transcription. The term 'transcriptional regulatory code' has been
      used to describe the interplay of these events in the complex control of
      transcription. With the maturation of methods for detecting in vivo protein-DNA
      interactions on a genome-wide scale, detailed maps of chromatin features and
      transcription factor localization over entire genomes of eukaryotic cells are
      enriching our understanding of the properties and nature of this transcriptional
      regulatory code. The rapidly growing number of maps has revealed the dynamic
      nature of nucleosome composition and chromatin remodeling at regulatory regions
      and highlighted some unexpected properties of transcriptional regulatory networks
      in eukaryotic cells.

PMID- 16647255
TI  - The use of chemical composition data in waste management planning--a case study.
AB  - As the waste industry continues to move from a disposal-based system to one based
      on a combination of recovery options, the need for information on the composition
      of waste increases and this is reflected by the amount of information on the
      physical composition of municipal solid wastes that is now available. However,
      there is far less information on the chemical composition of municipal solid
      waste. The results from a number of chemical surveys from Europe are compared and
      show a reasonable degree of agreement, but several problems were identified with
      the data. Chemical and physical compositional data are combined in a case study
      example to investigate the flow of key potential pollutants in an integrated
      solid waste management system that uses materials recycling, composting,
      incineration and landfilling. This case study has shown that an integrated waste
      management strategy diverts lead and cadmium away from composting and recycling
      to incineration, which effectively isolates these elements from the environment
      through efficient capture of the pollutants followed by secure landfilling or
      recycling of the residues. However, further work is needed to determine the
      distribution of mercury in incineration residues and its fate when the residues
      are landfilled.

PMID- 16647256
TI  - Dipeptidyl nitriles as human dipeptidyl peptidase I inhibitors.
AB  - Using a dipeptide nitrile scaffold we have identified a potent and selective
      inhibitor of human dipeptidyl peptidase I.

PMID- 16647257
TI  - Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular
      activity.
AB  - The disruption of the p53-Hdm2 protein-protein interaction induces cell growth
      arrest and apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione
      scaffold as a suitable template for inhibiting this interaction by binding to the
      Hdm2 protein. Several compounds have been made with improved potency, solubility,
      and cell-based activities.

PMID- 16647258
TI  - Racemic and chiral sulfoxides as potential prodrugs of 4-pyrone COX-2 inhibitors.
AB  - The preparation of the sulfoxide analogues 7, 8, and 9 and their enantiomerically
      pure forms is discussed as well as their ability to act as prodrugs of the potent
      and selective sulfone-containing COX-2 inhibitors 1, 2, and 3. Sulfoxide
      derivatives 7 and 9 were shown to be rapidly transformed in vivo into the
      corresponding sulfone derivatives 1 and 3, after oral administration to rats.

PMID- 16647259
TI  - Response of Drosophila to wasabi is mediated by painless, the fly homolog of
      mammalian TRPA1/ANKTM1.
AB  - A number of repellent compounds produced by plants elicit a spicy or pungent
      sensation in mammals . In several cases, this has been found to occur through
      activation of ion channels in the transient receptor potential (TRP) family . We
      report that isothiocyanate (ITC), the pungent ingredient of wasabi, is a
      repellent to the insect Drosophila melanogaster, and that the painless gene,
      previously known to be required for larval nociception, is required for this
      avoidance behavior. A painless reporter gene is expressed in gustatory receptor
      neurons of the labial palpus, tarsus, and wing anterior margin, but not in
      olfactory receptor neurons, suggesting a gustatory role. Indeed, painless
      expression overlaps with a variety of gustatory-receptor gene reporters. Some,
      such as Gr66a, are known to be expressed in neurons that mediate gustatory
      repulsion . painless mutants are not taste blind; they show normal aversive
      gustatory behavior with salt and quinine and attractive responses to sugars and
      capsaicin. The painless gene is an evolutionary homolog of the mammalian "wasabi
      receptor" TRPA1/ANKTM1 , also thought to be involved in nociception. Our results
      suggest that the stinging sensation of isothiocyanate is caused by activation of
      an evolutionarily conserved molecular pathway that is also used for nociception.

PMID- 16647260
TI  - Cluster analysis for the extraction of sagittal gait patterns in children with
      cerebral palsy.
AB  - Classification of gait disorders would facilitate standardisation of gait
      management and communication across professional boundaries. In the past, such
      classification was undertaken using a variety of approaches with often unclear
      methodology and validation procedures. This study describes the application of
      hierarchical cluster analysis on sagittal kinematic gait data derived from 56
      children with cerebral palsy and 11 neurologically intact children in order to
      define existing clusters of gait patterns in the children's data. A structured
      rationale was developed to seek and validate the optimal number of homogenous
      gait types within the data resulting in 13 different gait clusters that were
      organised into 'crouch gait type', 'equinus gait type' and 'other gait type'.
      Applying cluster analysis in combination with visual assessment of gait data and
      a structured protocol, we have been able to define valid gait groupings.

PMID- 16647261
TI  - Intra-articular angioleiomyoma of the knee: a case report.
AB  - We report a rare case of angioleiomyoma that occurred in the intra-articular
      portion of the knee joint. A 43-year-old female was referred to us with a 3-year
      history of recurrent pain and a loss of full extension of the right knee.
      Physical examinations revealed swelling and restriction of active full extension.
      Magnetic resonance imaging (MRI) revealed an intra-articular tumor. Surgical
      excision was performed, and the histology was characteristic of an
      angioleiomyoma. The patient became asymptomatic after the operation. At 2-year
      follow-up after the operation, no recurrence has developed.

PMID- 16647262
TI  - A biomechanical study comparing a raft of 3.5 mm cortical screws with 6.5 mm
      cancellous screws in depressed tibial plateau fractures.
AB  - There has been a recent trend towards using a raft of small diameter 3.5mm
      cortical screws for supporting depressed tibial plateau fractures (Schatzker type
      III). Our aim was to compare the biomechanical properties of a raft of 3.5 mm
      cortical screws with that of 6.5 mm cancellous screws in a synthetic bone model.
      Ten rigid polyurethane foam (sawbone) blocks, with a density simulating
      osteoporotic bone and ten blocks with a density simulating normal density bone
      were obtained. A Schatzker type III fracture was created in each block. The
      fracture fragments were then elevated and supported using two 6.5 mm cancellous
      screws in ten blocks and four 3.5 mm cortical screws in the remaining. The
      fractures were loaded using a Lloyd testing machine. The mean force needed to
      produce a depression of 5 mm was 700.8 N with the four-screw construct and 512.4
      N with the two-screw construct in the osteoporotic model. This difference was
      highly statistically significant (p = 0.009). The mean force required to produce
      the same depression was 1878.2 N with the two-screw construct and 1938.2 N with
      the four-screw construct in the non-osteoporotic model. Though the difference was
      not statistically significant (p = 0.42), an increased fragmentation of the
      synthetic bone fragments was noticed with the two-screw construct but not with
      the four-screw construct. A raft of four 3.5 mm cortical screws is
      biomechanically stronger than two 6.5 mm cancellous screws in resisting axial
      compression in osteoporotic bone.

PMID- 16647263
TI  - High-mannose-type glycan modifications of dihydrofolate reductase using glycan
      methotrexate conjugates.
AB  - Various high-mannose-type glycan modifications of dihydrofolate reductase (DHFR)
      were achieved by ligand-based approach using glycan-methotrexate (MTX) conjugates
      as tight binding glycan bearing ligands for DHFR. The resulting glycan-MTX
      conjugates and the corresponding artificial glycoproteins could be useful as
      oligosaccharide- and glycoprotein-probes to perform quantitative analysis of
      glycan recognizing protein such as lectins, glycosyltransferases or glycosidases.
      Moreover, artificial glycoproteins having two different high-mannose-type glycans
      were developed for the first time by a combination of two different types of
      glycan modification strategies.

PMID- 16647264
TI  - New 1,2,3,9-tetrahydro-4H-carbazol-4-one derivatives: analogues of HEAT as
      ligands for the alpha1-adrenergic receptor subtypes.
AB  - With the aim to develop new ligands able to discriminate among the three subtypes
      of alpha1-adrenergic receptors (alpha1A-AR, alpha1B-AR, and alpha1D-AR), a series
      of new 1,2,3,9-tetrahydro-4H-carbazol-4-ones bearing a 3-[[[2-(4
      hydroxyphenyl)ethyl]amino]methyl] or a 3-[[4-(2-substitutedphenyl)piperazin-1
      yl]methyl] side chain were synthesized. The general structure of the new
      compounds is reminiscent of HEAT and RN5, two potent alpha1-AR antagonists which
      show high affinities for all three alpha1-AR subtypes. Some derivatives in which
      one ring of the tetrahydrocarbazolone system was opened were also prepared.
      Compounds were tested in radioligand binding assays on human cloned alpha1A-AR,
      alpha1B-AR, and alpha1D-AR subtypes stably expressed in HEK293 cells. They showed
      moderate to good affinities, although their selectivity among the receptor
      subtypes hardly reached one order of magnitude.

PMID- 16647265
TI  - Locus prl5 improves lodging resistance of rice by delaying senescence and
      increasing carbohydrate reaccumulation.
AB  - We investigated the reason for carbohydrate retention in the stem of rice (Oryza
      sativa L.) at full-ripe stage in a near-isogenic line (NIL63) carrying prl5,
      which confers lodging resistance without yield loss. NIL63 showed higher lodging
      resistance than Nipponbare (control) without reduced yield. At heading, the
      carbohydrate content in the NIL63 stem (culm and leaf sheathes) was the same as
      in Nipponbare. At 2 weeks after heading, the carbohydrate content in NIL63 was
      significantly higher than in Nipponbare. At 4 weeks after heading, the
      carbohydrate content in NIL63 had decreased to near the level in Nipponbare. At 6
      weeks after heading, NIL63 showed higher carbohydrate reaccumulation. Chlorophyll
      degradation in the leaf blades of NIL63 was slower, and the chlorophyll content
      at 6 weeks after heading was higher than in Nipponbare. These results suggest
      that the delay in leaf senescence by prl5 results in carbohydrate reaccumulation
      in the stem after grain filling, increasing lodging resistance.

PMID- 16647266
TI  - Endoplasmic reticulum targeted GFP reveals ER organization in tobacco NT-1 cells
      during cell division.
AB  - The endoplasmic reticulum (ER) of plant cells undergoes a drastic reorganization
      during cell division. In tobacco NT-1 cells that stably express a GFP construct
      targeted to the ER, we have mapped the reorganization of ER that occurs during
      mitosis and cytokinesis with confocal laser scanning microscopy. During division,
      the ER and nuclear envelope do not vesiculate. Instead, tubules of ER accumulate
      around the chromosomes after the nuclear envelope breaks down, with these tubules
      aligning parallel to the microtubules of the mitotic spindle. In cytokinesis, the
      phragmoplast is particularly rich in ER, and the transnuclear channels and
      invaginations present in many interphase cells appear to develop from ER tubules
      trapped in the developing phragmoplast. Drug studies, using oryzalin and
      latrunculin to disrupt the microtubules and actin microfilaments, respectively,
      demonstrate that during division, the arrangement of ER is controlled by
      microtubules and not by actin, which is the reverse of the situation in
      interphase cells.

PMID- 16647267
TI  - Pharmacological evidence for activation of phospholipid and small GTP binding
      protein signalling cascades by Nod factors.
AB  - The effects of lipo-chitin oligosaccharide Nod factors (NodNGR[S] from Rhizobium
      sp. NGR234) on root hair deformation in Vigna unguiculata (L.) Walp. were studied
      using pharmacological agents to mimic and/or inhibit their action. It was
      hypothesised that the rearrangement of the cytoskeleton seen during Nod factor
      induced root hair deformation is modulated by protein kinase C, monomeric G
      proteins of the Rho superfamily and the location and amount of
      phosphatidylinositol 3-phosphates (PI3Ps). This hypothesis is supported by the
      following observations. The protein kinase C activators, 12-deoxyphorbol 13
      acetate (DPA) and diacylglycerol kinase inhibitor 1, stimulated root hair
      deformation to a level similar to that seen with Nod factors or mastoparan,
      whereas the inhibitor Go 6976 inhibited root hair deformations induced by
      NodNGR[S], mastoparan, DPA and diacylglycerol kinase inhibitor 1. The Ras
      antagonists mevastatin and sulindac sulphide, and the Rho antagonist exoenzyme C3
      toxin from Clostridium botulinum all inhibited Nod factor stimulated root hair
      deformation. Pasteurella multocida toxin activates Rho and stimulated root hair
      deformation, this stimulation was inhibited by both neomycin and exoenzyme C3
      toxin. The PI3 kinase inhibitors, wortmannin and LY-294002 attenuated Nod factor
      induced root hair deformation. These studies were complemented with actin
      immunoprecipitations of root hair enriched microsomal membrane preparations from
      V. unguiculata which pulled down small GTP binding proteins. Root hair
      deformation is an important early stage in the formation of nitrogen fixing
      nodules and this study highlights that these processes may depend on signalling
      cascades involving phospholipids and small GTP binding proteins.

PMID- 16647268
TI  - Increased NaCl-induced interleukin-8 production by human bronchial epithelial
      cells is enhanced by the DeltaF508/W1282X mutation of the cystic fibrosis
      transmembrane conductance regulator gene.
AB  - A satisfactory model describing the airway surface fluid (ASF) in the airways of
      persons with cystic fibrosis (CF) remains to be established due to theoretical
      challenges to both the "Hydration Hypothesis" and the "Salt Hypothesis."
      Irrespective of these models, inhaled hypertonic saline is often used to
      facilitate clearance of inspissated secretions. Hypertonicity induces interleukin
      8 (IL-8) expression, a potent chemokine for neutrophils. The objectives of this
      study were: (i) to determine the relative contribution of three potential cis
      regulatory elements in the regulation of NaCl-induced IL-8 production in BEAS-2B
      human bronchial epithelial cells, (ii) to compare NaCl-induced IL-8 expression in
      IB3-1 bronchial epithelial cells, which have the DeltaF508/W1282X mutation of the
      CF transmembrane conductance regulator (CFTR) gene, with that in C38 cells, which
      are IB3-1 cells stably transfected with a truncated but functional CFTR gene, and
      (iii) to compare equal osmolar concentrations of NaCl and D-sorbitol in the
      induction of IL-8 in all three cell types. In human bronchial epithelial cells,
      binding sites for NFkappaB, AP-1, and NF-IL6 in the 5'-flanking region of the IL
      8 promoter are necessary for optimal NaCl induction of IL-8. Human bronchial
      epithelial cells with the DeltaF508/W1282X CFTR mutation produce an exaggerated
      amount of basal and NaCl-induced IL-8.

PMID- 16647269
TI  - A conserved role of Caenorhabditis elegans CDC-48 in ER-associated protein
      degradation.
AB  - Protein degradation mediated by the ubiquitin/proteasome system is essential for
      the elimination of misfolded proteins from the endoplasmic reticulum (ER) to
      adapt to ER stress. It has been reported that the AAA ATPase p97/VCP/CDC48 is
      required in this pathway for protein dislocation across the ER membrane and
      subsequent ubiquitin dependent degradation by the 26S proteasome in the cytosol.
      Throughout ER-associated protein degradation, p97 cooperates with a binary
      Ufd1/Npl4-complex. In Caenorhabditis elegans two homologs of p97, designated CDC
      48.1 and CDC-48.2, exist. Our results indicate that both p97 homologs interact
      with UFD-1/NPL-4 in a similar CDC-48(UFD-1/NPL-4) complex. RNAi mediated
      depletion of the corresponding genes induces ER stress resulting in
      hypersensitivity to conditions which induce increased levels of unfolded proteins
      in the ER lumen. Together, these data suggest an evolutionarily conserved retro
      translocation machinery at the endoplasmic reticulum.

PMID- 16647270
TI  - Autoinhibitory and other autoregulatory elements within the dynein motor domain.
AB  - The dyneins are a family of microtubule motor proteins. The motor domain, which
      represents the C-terminal 2/3 of the dynein heavy chain, exhibits homology to the
      AAA family of ATPases. It consists of a ring of six related but divergent AAA+
      units, with two substantial sized protruding projections, the stem, or tail,
      which anchors the protein to diverse subcellular sites, and the stalk, which
      binds microtubules. This article reviews recent efforts to probe the mechanism by
      which the dyneins produce force, and work from the authors' lab regarding long
      range conformational regulation of dynein enzymatic activity.

PMID- 16647271
TI  - The impact of affect and frequency on lexical decision: the role of the amygdala
      and inferior frontal cortex.
AB  - The current study used event-related fMRI to examine BOLD responses associated
      with two factors that behaviorally determine speed of lexical decision: frequency
      and emotion. Thirteen healthy adults performed a visual lexical decision task,
      discriminating between words and orthographically and phonologically legal
      nonwords. The study involved a 2 (Frequency: high and low) x 3 (Emotional
      arousal: highly negative, mildly negative, and neutral words) design with word
      categories matched for number of letters and concreteness. There were significant
      main effects for both frequency and emotion in lexical decision reaction times
      but no significant interaction. Negative word lexical decisions were associated
      with increased activation in bilateral amygdala and middle temporal cortex as
      well as rostral anterior and posterior cingulate cortex. Low-frequency word
      lexical decisions, relative to high-frequency word lexical decisions, were
      associated with increased bilateral activity in inferior frontal cortex. Inferior
      frontal cortex activation was particularly low during lexical decision for high
      frequency emotional words but significant for high-frequency neutral emotional
      words. We suggest that this is because the semantic representation of high
      frequency emotional words may receive sufficient additional augmentation via the
      reciprocal activation from the amygdala such that selective augmentation by
      inferior frontal cortex to achieve lexical decision is unnecessary.

PMID- 16647272
TI  - The parcellation of cortical areas using replicator dynamics in fMRI.
AB  - In this paper, we show that replicator dynamics can be used as an exploratory
      analysis tool to detect subregions of cortical areas on the basis of the
      similarity between fMRI time series. As similarity measure, we propose to use
      canonical correlation, a multivariate extension to the typically employed
      Pearson's correlation coefficient. We applied the replicator process to data
      obtained from two different experimental paradigms in the search for subregions
      within the left lateral frontal cortex (LFC). In both cases, the replicator
      process resulted in a parcellation that corresponds to a recently suggested
      subdivision of the LFC in anterior-posterior direction. Most notably, these
      results were very consistent when compared across different measurements of a
      single subject and across a group of subjects.

PMID- 16647273
TI  - Phylogenetic estimation under codon models can be biased by codon usage
      heterogeneity.
AB  - In theory, codon models that account for the dependence of nucleotide
      substitutions between codon positions as well as differences between synonymous
      and non-synonymous changes best describe the sequence evolution in protein coding
      genes. However, in practice we know little about the degree to which violations
      of the assumptions of codon model-based estimates occur, and how significant
      these artifacts may be. In nucleotide-based phylogenies from first and second
      codon positions in a concatenated plastid gene data set, two distantly related
      taxa--dinoflagellate and haptophyte plastids--were robustly grouped together.
      This artifactual grouping is attributed to the parallel heterogeneity in leucine
      (Leu) and serine (Ser) codon usages in the data set. Here, by using this data
      set, we demonstrated that codon-based phylogenetic estimations are seriously
      biased, robustly uniting the dinoflagellate and haptophyte plastids into a
      monophyletic clade, when the model assumption of homogeneity of codon composition
      was violated. Our results suggest that similar phylogenetic artifacts may occur
      via codon usage heterogeneity in any amino acids in codon model-based
      estimations. We advise that homogeneity in codon usage across taxa in a data set
      be confirmed before codon model-based phylogenetic estimation is attempted.

PMID- 16647274
TI  - Molecular evidence for recent divergence of Lake Tanganyika endemic crabs
      (Decapoda: Platythelphusidae).

PMID- 16647275
TI  - Relationship between morphological taxonomy and molecular divergence within
      Crustacea: proposal of a molecular threshold to help species delimitation.
AB  - With today's technology for production of molecular sequences, DNA taxonomy and
      barcoding arose as a new tool for evolutionary biology and ecology. However,
      their validities still need to be empirically evaluated. Of most importance is
      the strength of the correlation between morphological taxonomy and molecular
      divergence and the possibility to define some molecular thresholds. Here, we
      report measurements of this correlation for two mitochondrial genes (COI and 16S
      rRNA) within the sub-phylum Crustacea. Perl scripts were developed to ensure
      objectivity, reproducibility, and exhaustiveness of our tests. Our analysis
      reveals a general correlation between molecular divergence and taxonomy. This
      correlation is particularly high for shallow taxonomic levels allowing us to
      propose a COI universal crustacean threshold to help species delimitation. At
      higher taxonomic levels this correlation decreases, particularly when comparing
      different families. Those results plead for DNA use in taxonomy and suggest an
      operational method to help crustacean species delimitation that is linked to the
      phylogenetic species definition. This pragmatic tool is expected to fine tune the
      present classification, and not, as some would have believed, to tear it apart.

PMID- 16647276
TI  - Air travel and seizure frequency for individuals with epilepsy.
AB  - This study investigated whether air travel is associated with an increase in
      seizures for individuals with epilepsy. Thirty-seven participants monitored their
      seizure frequency for one week prior to flying and for one week after flying. For
      the sample as a whole, seizures were significantly more common after flying
      (p=.02). No seizures were reported as occurring during flight. Participants who
      experienced an increase in seizures after flying compared to those who did not
      (a) had a higher baseline of seizure frequency (p=.004), (b) were more likely to
      have previously experienced an increase in seizures after flying (p=.001), (c)
      were more worried about having a seizure while flying (p=.001) and (d) were more
      likely to avoid air travel (p=.02). Participants with complete seizure control
      prior to flying did not experience seizures after flying. Distance traveled, time
      zones crossed, duration of flight and direction of flight were not significantly
      different for those with seizure increase than for those without such an
      increase. This study suggests that air travel promotes an increase in seizures
      for those with a prior history of flight related seizures and a relatively high
      baseline seizure frequency.

PMID- 16647277
TI  - Elevated serum levels of soluble interleukin-4 receptor in osteoarthritis.
AB  - OBJECTIVE: To test the importance of the interleukin-4 (IL-4)/IL-4 receptor (IL
      4R) system in osteoarthritis (OA) we evaluated soluble IL-4R (sIL-4R) levels in
      sera of patients with different forms of OA and healthy individuals. METHODS: We
      recruited: 141 patients with hand OA, 70 with nodal and 71 with erosive hand OA;
      64 patients undergoing total joint replacement, 34 with hip and 30 with knee OA;
      and 38 ethnically and geographically age-matched healthy individuals [normal
      controls (NC)]. RESULTS: Serum sIL-4R concentration was found to be significantly
      higher in all OA patients than that in NC. When patients were divided into four
      subgroups (nodal, erosive, hip and knee OA) significant differences were present
      when comparing NC with each subgroup. This was true also when small-joint OA
      groups were compared with large-joint OA groups, the latter being associated with
      higher IL-4R levels. CONCLUSIONS: We found increased levels of sIL-4R in OA
      patients compared with healthy individuals. We speculate that this reduces
      availability of IL-4, and its effects on chondrocytes.

PMID- 16647278
TI  - Is cartilage thickness different in young subjects with and without
      patellofemoral pain?
AB  - OBJECTIVE: To determine the differences in load-bearing patellofemoral joint
      cartilage thickness between genders. To determine the differences in load-bearing
      cartilage thickness between pain-free controls and individuals with
      patellofemoral pain. METHODS: The articular cartilage thickness of the patella
      and anterior femur was estimated from magnetic resonance images in 16 young, pain
      free control subjects (eight males, eight females) and 34 young individuals with
      patellofemoral pain (12 males, 22 females). The average age of all subjects was
      28+/-4 years. The cartilage surfaces were divided into regions approximating the
      location of patellofemoral joint contact during knee flexion. The mean and peak
      cartilage thicknesses of each region were computed and compared using a repeated
      measures Analysis of Variance. RESULTS: On average, males had 22% and 23% thicker
      cartilage than females in the patella (P < 0.01) and femur (P < 0.05),
      respectively. Male control subjects had 18% greater peak patellar cartilage
      thickness than males with patellofemoral pain (P < 0.05); however, we did not
      detect differences in patellar cartilage thickness between female control
      subjects and females with patellofemoral pain (P = 0.45). We detected no
      significant differences in femoral cartilage thickness between the control and
      pain groups. CONCLUSIONS: Thin cartilage at the patella may be one mechanism of
      patellofemoral pain in male subjects, but is unlikely to be a dominant factor in
      the development of pain in the female population.

PMID- 16647279
TI  - Expression of the cadherin-11 gene is a discriminative factor between articular
      and growth plate chondrocytes.
AB  - OBJECTIVE: Calcification of hypertrophic chondrocytes is the final step in the
      differentiation of growth plates, although the precise mechanism is not known. We
      have established two growth plate-derived chondrocyte cell lines, MMR14 and
      MMR17, from p53-/- mice (Nakamata T, Aoyama T, Okamoto T, Hosaka T, Nishijo K,
      Nakayama T, et al. In vitro demonstration of cell-to-cell interaction in growth
      plate cartilage using chondrocytes established from p53-/- mice. J Bone Miner Res
      2003;18:97-107). Prolonged in vitro culture produced calcified nodules in MMR14,
      but not in MMR17. Factors responsible for the difference in calcification between
      the two cell lines may also be involved in the physiological calcification in
      growth plate. DESIGN: Gene expression profiles of MMR14 and MMR17 were compared
      using a cDNA microarray to identify candidate genes involved in the calcification
      process. RESULTS: Forty-five genes were identified as upregulated in MMR14,
      including the cadherin-11 (Cdh-11) gene. The expression of Cdh-11 in MMR14 was
      detected in cell-cell junctions, while no expression was observed in MMR17.
      Primary cultured chondrocytes from growth plate (GC) also expressed the Cdh-11,
      and the staining of Cdh-11 was observed in the late hypertrophic zone of growth
      plate. Cell aggregation assays showed that chondrocytes required Ca2+ to form
      nodules, and knockdown of the Cdh-11 gene expression using short interfering RNA
      inhibited the formation of calcified nodules in MMR14. The introduction of Cdh-11
      into MMR17 failed to produce calcified nodules indicating that Cdh-11 is one, but
      not the sole, factor responsible for the production of calcified nodules.
      CONCLUSION: Although the physiological role is still unclear, Cdh-11 is a
      discriminative factor between articular and growth plate chondrocytes.

PMID- 16647280
TI  - Role of muscarinic M1 receptors in inhibitory avoidance and contextual fear
      conditioning.
AB  - The objective of the present study was to observe the effects of pre-training or
      post-training administration of dicyclomine, a M1 muscarinic antagonist, on
      inhibitory avoidance (IA) and contextual fear conditioning (CFC) and to
      investigate if the effects observed with the pre-training administration of
      dicyclomine are state-dependent. For each behavioral procedure (IA and CFC)
      groups of Wistar male rats were treated with saline or dicyclomine either 30 min
      before training (pre-training), immediately after training or 30 min before
      training/30 min before test (pre-training/pre-test). The animals were tested 24 h
      after training. The acquisition of IA and CFC was impaired by pre-training
      administration of dicyclomine. The consolidation of both tasks was not affected
      by dicyclomine given immediately after training. Pre-training/pre-test
      administration of dicyclomine impaired both tasks, an effect similar to that
      observed in the group which only received pre-training administration. Pre-test
      treatment induced dissociation between both tasks, impairing CFC retrieval,
      without interfering with the animals avoidance response. These results show that
      the dicyclomine did not affect IA and CFC consolidation, suggesting specific
      involvement of M1 muscarinic receptor only in acquisition these tasks, and these
      effects was not state-dependent. However, it is possible that the retrieval of
      these tasks may be mediated, at least in part, by different neurochemical
      mechanisms and may be dissociated by dicyclomine.

PMID- 16647281
TI  - Posttraining handling facilitates memory for auditory-cue fear conditioning in
      rats.
AB  - A large number of studies have indicated that stress exposure or the
      administration of stress hormones and other neuroactive drugs immediately after a
      learning experience modulates the consolidation of long-term memory. However,
      there has been little investigation into how arousal induced by handling of the
      animals in order to administer these drugs affects memory. Therefore, the present
      study examined whether the posttraining injection or handling procedure per se
      affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley
      rats, which had been pre-handled on three days for 1 min each prior to
      conditioning, received three pairings of a single-frequency auditory stimulus and
      footshock, followed immediately by either a subcutaneous injection of a vehicle
      solution or brief handling without injection. A control group was placed back
      into their home cages without receiving any posttraining treatment. Retention was
      tested 24 h later in a novel chamber and suppression of ongoing motor behavior
      during a 10-s presentation of the auditory-cue served as the measure of
      conditioned fear. Animals that received posttraining injection or handling did
      not differ from each other but showed significantly less stimulus-induced
      movement compared to the non-handled control group. These findings thus indicate
      that the posttraining injection or handling procedure is sufficiently arousing or
      stressful to facilitate memory consolidation of auditory-cue classical fear
      conditioning.

PMID- 16647282
TI  - A daytime nap containing solely non-REM sleep enhances declarative but not
      procedural memory.
AB  - The specialized role that sleep-specific brain physiology plays in memory
      processing is being rapidly clarified with a greater understanding of the
      dynamic, complex, and exquisitely orchestrated brain state that emerges during
      sleep. Behaviorally, the facilitative role of non-REM (NREM) sleep (primarily
      slow wave sleep) for declarative but not procedural memory performance in humans
      has been demonstrated in a number of nocturnal sleep studies. However, subjects
      in these studies were tested after periods of sleep that contained REM sleep in
      addition to NREM sleep, and comparison wake groups were subjected to mild sleep
      deprivation. To add some clarity to the findings of these nocturnal studies, we
      assessed performance on declarative and procedural memory tasks following a
      daytime training-retest interval containing either a short nap that included NREM
      without REM sleep, or wakefulness. Consistent with previous findings we show
      that, after a comparatively brief sleep episode, subjects that take a nap improve
      more on a declarative memory task than subjects that stay awake, but that
      improvement on a procedural memory task is the same regardless of whether
      subjects take a nap or remain awake. Slow wave sleep was the only sleep parameter
      to correlate positively with declarative memory improvement. These findings are
      discussed with reference to the general benefits of napping and within the
      broader context of a growing literature suggesting a role for NREM-specific
      physiology for the processing of declarative memory.

PMID- 16647283
TI  - Cellular mechanisms that determine selective RGS protein regulation of G protein
      coupled receptor signaling.
AB  - Regulators of G protein signaling (RGS proteins) bind directly to activated
      Galpha subunits to inhibit their signaling. However, recent findings show that
      RGS proteins selectively regulate signaling by certain G protein-coupled
      receptors (GPCRs) in cells, irrespective of the coupled G protein. New studies
      support an emerging model that suggests RGS proteins utilize both direct and
      indirect mechanisms to form stable functional pairs with preferred GPCRs to
      selectively modulate the signaling functions of those receptors and linked G
      proteins. Here, we discuss these findings and their implications for established
      models of GPCR signaling.

PMID- 16647284
TI  - Radiochemical HPLC detection of arginine metabolism: measurement of nitric oxide
      synthesis and arginase activity in vascular tissue.
AB  - Nitric oxide (NO) plays a key role in vascular homeostasis. Accurate measurement
      of NO production by endothelial nitric oxide synthase (eNOS) is critical for the
      investigation of vascular disease mechanisms using genetically modified animal
      models. Previous assays of NO production measuring the conversion of arginine to
      citrulline have required homogenisation of tissue and reconstitution with
      cofactors including NADPH and tetrahydrobiopterin. However, the activity and
      regulation of NOS in vivo is critically dependant on tissue levels of these
      cofactors. Therefore, understanding eNOS regulation requires assays of NO
      production in intact vascular tissue that do not depend on the addition of
      exogenous cofactors and have sufficient sensitivity and specificity. We describe
      a novel technique, using radiochemical detection of arginine to citrulline
      conversion, to measure NO production within intact mouse aortas, without
      exogenous cofactors. We demonstrate the presence of arginase activity in mouse
      aortas which has the potential to confound this assay. Furthermore, we describe
      the use of N-hydroxy-nor-L-arginine (nor-NOHA) to inhibit arginase and permit
      specific detection of NO production in intact mouse tissue. Using this technique
      we demonstrate a 2.4-fold increase in NO production in aortas of transgenic mice
      overexpressing eNOS in the endothelium, and show that this technique has high
      specificity and high sensitivity for detection of in situ NO synthesis by eNOS in
      mouse vascular tissue. These results have important implications for the
      investigation of NOS regulation in cells and tissues.

PMID- 16647285
TI  - Effect of temperature acclimation on metabolism and hemocyanin binding affinities
      in two crayfish, Procambarus clarkii and Procambarus zonangulus.
AB  - Procambarus clarkii and Procambarus zonangulus are two of the most widespread
      crayfish species in North America. In regions where their ranges overlap species
      composition can vary greatly. The physiological basis for this variable species
      composition is unknown. Temperature and oxygen level are two parameters that vary
      in shallow water habitats. We examined the metabolic rate and hemocyanin binding
      affinities in relation to thermal history. Temperature acclimation did not have
      the predicted effect on metabolic rate. Acclimation to high temperature (30
      degrees C) decreased metabolic rate at 35 degrees C for both species. Low
      temperature acclimation (10 degrees C) resulted in 20% mortality in P. clarkii
      and 100% mortality in P. zonangulus when exposed to 35 degrees C. The range of P.
      clarkii is known to extend farther south than that of P. zonangulus, and this
      response may be a consequence of adaptations to higher temperatures in this
      range. Hemocyanin binding affinity was directly affected by assay and acclimation
      temperature. The highest P(50) values were recorded for crayfish of both species
      acclimated to 10 degrees C and assayed at 30 degrees C. There was also a shift in
      the isoelectric points of hemolymph proteins (possibly due to structural changes)
      that correlated with and an increase in the hemocyanin binding affinity following
      acclimation to high temperatures (30 degrees C) in both species.

PMID- 16647286
TI  - Foxl2 function in ovarian development.
AB  - Foxl2 is a forkhead transcription factor essential for proper reproductive
      function in females. Human patients carrying mutations in the FOXL2 gene display
      blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal
      dominant disease associated with eyelid defects and premature ovarian failure in
      females. Recently, animal models for BPES have been developed that in combination
      with a catalogue of human FOXL2 mutations provide further insight into its
      molecular function. Mice homozygous mutant for Foxl2 display craniofacial
      malformations and female infertility. The analysis of the murine phenotype has
      revealed that Foxl2 is required for granulosa cell function. These ovarian
      somatic cells surround and nourish the oocyte and play an important role in
      follicle formation and activation. Mutations upstream of FOXL2 in humans, not
      affecting the coding sequence itself, have also been shown to cause BPES, which
      points to the existence of a distant regulatory element necessary for proper gene
      expression. The same regulatory sequences may be deleted in the goat polled
      intersex syndrome (PIS), in which FoxL2 expression is severely reduced. Sequence
      comparison of FoxL2 from several vertebrate species has shown that it is a highly
      conserved gene involved in ovary development. Thus, the detailed understanding of
      Foxl2 function and regulation and the identification of its transcriptional
      targets may open new avenues for the treatment of female infertility in the
      future.

PMID- 16647287
TI  - The association between morbidity and radiographic hand osteoarthritis: a
      population-based study.
AB  - OBJECTIVES: Osteoarthritis is the most common form of joint disease and is
      considered to be a risk factor for other morbidities. We performed a population
      based study to evaluate the association between morbidity and radiographic hand
      osteoarthritis. METHODS: Our population consisted of Chuvashians residing in
      peripheral villages of the Russian Federation. The investigated cohort included
      434 males aged 18-86 years and 385 females aged 18-84 years. Osteoarthritis
      development was evaluated using the Kellgren and Lawrence grading scheme.
      Morbidity data was attained from their medical records and divided into 14
      categories by an experienced research physician. To explore the relationship
      between morbidity and age-adjusted radiographic hand osteoarthritis score, one
      way analysis of variance was used, with hand osteoarthritis score as a dependent
      variable and individuals affected vs. non-affected with the specific disease as
      an independent (grouping) variable. RESULTS AND CONCLUSIONS: Statistically
      significant evidence linking radiographic hand osteoarthritis and morbidities was
      found in patients with ischemic heart disease and gastrointestinal diseases. Our
      research indicates that individuals with ischemic heart disease have higher
      values of radiographic hand osteoarthritis, compared to lower values in
      individuals with gastrointestinal diseases. Additional research is needed to
      understand the biological mechanisms of the association between morbidity and
      osteoarthritis.

PMID- 16647288
TI  - Polystyrene/Fe3O4 magnetic emulsion and nanocomposite prepared by ultrasonically
      initiated miniemulsion polymerization.
AB  - Ultrasonically initiated miniemulsion polymerization of styrene in the presence
      of Fe3O4 nanoparticles was successfully employed to prepare polystyrene
      (PS)/Fe3O4 magnetic emulsion and nanocomposite. The effects of Fe3O4
      nanoparticles on miniemulsion polymerization process, the structure, morphology
      and properties of PS/Fe3O4 nanocomposite were investigated. The increase in the
      amount of Fe3O4 nanoparticles drastically increases the polymerization rate due
      to that Fe3O4 nanoparticles increase the number of radicals and the cavitation
      bubbles. Polymerization kinetics of ultrasonically initiated miniemulsion
      polymerization is similar to that of conventional miniemulsion polymerization.
      PS/Fe3O4 magnetic emulsion consists of two types of particles: latex particles
      with Fe3O4 nanoparticles and latex particles with no encapsulated Fe3O4
      nanoparticles. Fe3O4 nanoparticles lower the molecular weight of PS and broaden
      the molecular weight and particle size distribution. Thermal stability of
      PS/Fe3O4 nanocomposite increases with the increase in Fe3O4 content. PS/Fe3O4
      emulsion and nanocomposite exhibit magnetic properties. PS/Fe3O4 magnetic
      particles can be separated from the magnetic emulsion by an external magnetic
      field and redispersed into the emulsion with agitation.

PMID- 16647289
TI  - Harnessing endophytes for industrial microbiology.
AB  - Endophytic microorganisms exist within the living tissues of most plant species.
      They are most abundant in rainforest plants. Novel endophytes usually have
      associated with them novel secondary natural products and/or processes. Muscodor
      is a novel endophytic fungal genus that produces bioactive volatile organic
      compounds (VOCs). This fungus, as well as its VOCs, has enormous potential for
      uses in agriculture, industry and medicine. Muscodor albus produces a mixture of
      VOCs that act synergistically to kill a wide variety of plant and human
      pathogenic fungi and bacteria. This mixture of gases consists primarily of
      various alcohols, acids, esters, ketones and lipids. Artificial mixtures of the
      VOCs mimic the biological effects of the fungal VOCs when tested against a wide
      range of fungal and bacterial pathogens. Many practical applications for
      'mycofumigation' by M. albus have been investigated and the fungus is now in the
      market place.

PMID- 16647290
TI  - A new species of Cardicola Short, 1953 (Digenea: Sanguinicolidae) parasitizing
      the Brazilian flathead, Percophis brasiliensis Quoy et Gaimard 1824, from the
      coasts of Mar del Plata, Argentina.
AB  - Cardicola ambrosioi n. sp. (Digenea: Sanguinicolidae) is found in the blood
      vessels of liver and gills of the Brazilian flathead, Percophis brasiliensis Quoy
      and Gaimard, 1824 (Pisces: Percophidae), from Mar del Plata, Argentina. Among the
      13 known species within Cardicola Short, 1953, the new species closely resembles
      Cardicola coridodacis Manter, 1954, from which it is distinguished by having a
      relatively shorter oesophagus, the vitellaria extending anteriorly to the nerve
      commissure, rather than to the end of anterior caeca, the female pore located
      closer to male pore, the latter situated medially instead of laterally and by
      possessing a larger Mehlis gland and a smaller seminal vesicle.

PMID- 16647291
TI  - The effect of ionic strength on the UV-vis spectrum of congo red in aqueous
      solution.
AB  - The major peak near 498 nm in the ultraviolet-visible spectrum of congo red in
      aqueous solution shifts toward the blue while the molar absorptivity of this peak
      decreases predictably with increasing ionic strength. The shift was observed for
      solutions in which ionic strength was varied from 0.0 to 1.8M using the uni
      univalent ionic compounds, NaCl, NaClO(4), KNO(3) and KBr separately. A plot of
      the log of the absorbance at the peak versus ionic strength was linear as well as
      a plot of the log of the wavelength of the major peak (shifted from 498 nm)
      versus the ionic strength. The slopes of each of these plots were somewhat
      different depending on the ionic compound.

PMID- 16647292
TI  - Characterization of the rat LDL receptor 5'-flanking region.
AB  - A 1.5-kb genomic DNA fragment corresponding to the 5'-flanking region of the rat
      LDL receptor gene was cloned and putative regulatory regions were identified. A
      major transcription start site was identified at -154 bp relative to the ATG
      translation initiation codon, within a region containing two thyroid hormone
      response element half-site motifs (2H-TRE). Binding of thyroid hormone receptors
      alpha and beta1 to this element was demonstrated. Mutations within this 2H-TRE
      region abolished basal transcription levels of the rat LDL receptor gene.
      Reporter gene studies indicated that the promoter region between -300 and -200
      bp, which contains one sterol response element (SRE) and two specificity protein
      1 sites (Sp1) sites, is crucial for basal transcription of the rat LDL receptor
      gene. The functionality of the SRE motif was confirmed using electrophoretic
      mobility shift assays and reporter gene studies.

PMID- 16647293
TI  - 15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI-
      and ABCA1-dependent cholesterol efflux from macrophages.
AB  - Elevated plasma levels of high-density lipoprotein cholesterol (HDL-C) are
      atheroprotective and HDL-dependent reverse cholesterol transport has been related
      to this effect. HDL particles may, however, undergo modifications that affect
      their biological activities. Lipoxygenases (LOs) belong to a family of lipid
      peroxidizing enzymes; among them, reticulocyte-type 15-lipoxygenase (15-LO-1)
      appears to play a pathophysiological role in atherosclerosis, as its expression
      is increased in atherosclerotic plaques and it has been shown to oxidize low
      density lipoproteins to an atherogenic form. In this work we investigated the
      impact of in vitro 15-lipoxygenase-catalyzed modification of HDL3 on their
      ability to act as cholesterol acceptor and found that 15-LO-modified HDL3 were
      less effective in mediating cholesterol efflux from lipid-laden J774 cells. A
      reduced binding of 15-LO-modified HDL3 to scavenger receptor class B, type I (SR
      BI), due to HDL apoproteins cross-linking, explained, at least in part, the
      observed reduction of cholesterol efflux. In addition, ATP-binding cassette
      transporter A1 (ABCA1)-mediated cholesterol efflux was also reduced, as a
      consequence of pre-beta-particles loss after HDL3 modification. These results
      suggest that 15-lipoxygenase might induce structural alterations of HDL3
      particles that impair their capability of triggering reverse cholesterol
      transport.

PMID- 16647294
TI  - A haptophyte bearing siliceous scales: ultrastructure and phylogenetic position
      of Hyalolithus neolepis gen. et sp. nov. (Prymnesiophyceae, Haptophyta).
AB  - A haptophyte alga bearing hyaline but conspicuous scales was discovered in
      surface water samples of Shiribeshi Seamount, Japan. X-ray elemental analysis
      confirmed that silica was the major element in these scales. These scales were
      hat-shaped, ellipsoidal in top view, 4-6mum wide and 5-7mum long, perforated by
      several small pores, and were deposited on cells in several layers. Beneath the
      siliceous scale layers, organic scales were present, which are typical of
      haptophytes. The cells were non-motile despite having two short flagella hidden
      in the scale case. The haptonema, extended over the scale case, and one and a
      half times the cell length. The intracellular features were typical of
      haptophytes, including the peripheral endoplasmic reticulum (PER), Golgi
      cisternae with peculiar dilations, and the flagellar apparatus. The siliceous
      scales were produced in vesicles in the posterior region of the cell. Motile
      cells lacking silica scales were observed occasionally when cultures were
      maintained at lower temperatures and under oligotrophic conditions. This alga was
      described as Hyalolithus neolepis gen. et sp. nov. Phylogenetic analysis using
      the SSU rDNA and rbcL gene sequences indicated that Hyalolithus is a member of
      the Prymnesiales and falls in a clade including Prymnesium, Platychrysis, and
      Chrysochromulina polylepis. Based on these results, the evolutionary implications
      of the presence of silicified scales in haptophytes is discussed.

PMID- 16647297
TI  - Adaptors discriminate mast-cell cytokine production from eicosanoid production
      and degranulation.
AB  - The Fc epsilonRI-dependent activation of nuclear factor (NF)kappaB is key for
      mast-cell cytokine production. The CARMA1-Bcl10-Malt1 adaptor complex regulates
      NFkappaB activation by antigen receptors in lymphocytes. A recent study reveals
      that the Bcl10-Malt1 complex promotes mast-cell interleukin-6 and tumor necrosis
      factor production, independent of degranulation, eicosanoid secretion or
      survival. The new findings place this complex at the forefront in discriminating
      between signals required for cytokine production and those required for mast-cell
      degranulation and eicosanoid production.

PMID- 16647298
TI  - Immunization of mice with a Mycobacterium tuberculosis genomic expression library
      results in lower bacterial load in lungs after challenge with BCG.
AB  - Tuberculosis is a serious infectious disease in many developing countries. The
      lack of an effective vaccine for preventing this disease has stimulated the
      search for new vaccine candidates against Mycobacterium tuberculosis. In the
      present work, the construction of a genomic expression library of M. tuberculosis
      in a eukaryotic expression vector was carried out. Immunization of Balb/c mice
      with a plasmid DNA pool from this library (containing 8360 clones) induced a
      significant IgG antibody response. Immunized mice were challenged by
      intratracheal route with 10(5) cfu of non-pathogenic Mycobacterium bovis BCG and
      were sacrificed 21 days post-challenge. Mice immunized with the genomic
      expression library showed a significant reduction of viable bacteria in lungs and
      less pulmonary tissue damage. Granulomas were not observed and the lungs had a
      more discrete perivascular inflammatory cell infiltrate compared to control mice.
      Results suggest that the genomic expression library contains genes encoding
      proteins that are protective against M. tuberculosis infection.

PMID- 16647299
TI  - Ex vivo selection and expansion of cells based on expression of a mutated inosine
      monophosphate dehydrogenase 2 after HIV vector transduction: effects on
      lymphocytes, monocytes, and CD34+ stem cells.
AB  - Hematopoietic progenitor cells (HPCs) represent an ideal target for gene therapy
      treatment of human immunodeficiency virus (HIV) infection. However, gene delivery
      into quiescent HPCs by retroviral or lentiviral vectors remains relatively poor.
      We evaluated a selection scheme based on the expression of a variant of inosine
      monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in the de novo
      purine biosynthesis pathway. As lymphocytes depend more than other cell types on
      de novo synthesis of purines, IMPDH inhibitors such as mycophenolic acid (MPA)
      can selectively expand lymphocytes overexpressing the enzymes. We used HIV
      vectors to deliver an IMPDH variant into T cells and HPCs. We showed that the
      transduced T cells became resistant to MPA selection. By expressing a short
      hairpin RNA gene targeted to the HIV gag transcript, the MPA-selected T cells
      became resistant to HIV-1 infection. Monocyte/macrophages derived from the
      transduced HPCs differentiated normally and exhibited normal function as measured
      by B7 up-regulation and phagocytosis when stimulated. Our results suggest that
      this system may be applicable as a selection strategy to enrich transduced T
      lymphocytes and mononuclear cells in vivo for HIV gene therapy.

PMID- 16647300
TI  - Seizure heralding functional recovery in a patient with apallic syndrome: A case
      report with retrospective-prospective observation.
AB  - BACKGROUND: It has been suggested that there exists a close relationship between
      seizure discharges and functional recovery from brain injury, and that paroxysmal
      bombardment in late seizures may herald functional recovery or may "kick-start"
      recovery. CASE REPORT: We report the case of a 52-year-old patient who, following
      a subarachnoid hemorrhage and multiple surgeries, experienced discernible apallic
      syndrome of long duration. His hospitalization is well documented. The patient
      underwent protracted, intense rehabilitation, but he remained in this prolonged
      state of loss of consciousness and behavioral passivity until he experienced a
      series of periodic seizures. Widespread improvement in his cognitive and
      functional abilities coincided closely with the seizure activity. The literature
      on this topic is reviewed. CONCLUSION: This case confirms the close relationship
      between seizure discharges and functional recovery reported in preclinical
      literature.

PMID- 16647301
TI  - Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1
      year follow-up.
AB  - The present study was conducted to evaluate the long-term effects of low-dose
      topiramate (TPM) monotherapy on the cognitive function of epilepsy patients.
      Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100
      mg/day. Cognitive tests were performed twice, at baseline and 1 year after
      starting medication. Thirty-six patients completed the follow-up
      neuropsychological tests. After a year of treatment, 16 patients (44%) complained
      of cognitive problems. Although it improved seizure frequency and EEG
      abnormalities, TPM had significantly negative effects on the digit span and
      verbal fluency tests. These cognitive effects were dose-related and significantly
      improved after withdrawal from TPM and substitution with older antiepileptic
      drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on
      working memory and verbal fluency.

PMID- 16647302
TI  - Effect of vagus nerve stimulation on creativity and cognitive flexibility.
AB  - OBJECTIVE: The purpose of this study was to determine whether vagus nerve
      stimulation influences cognitive flexibility and creativity. METHODS: Ten
      subjects, in whom vagus nerve stimulators had been implanted for the treatment of
      intractable seizures, performed tasks that assessed cognitive flexibility
      (solving anagrams), creativity (Torrance Test), and memory (Hopkins Verbal
      Learning Test) during actual and sham vagus nerve stimulation. RESULTS: Vagus
      nerve stimulation impaired cognitive flexibility and creativity, but these
      results could not be explained by the induction of a general encephalopathy
      because VNS did not impair learning and improved retention. CONCLUSIONS: The
      means by which vagus nerve stimulation impairs cognitive flexibility and creative
      thinking is probably related to increased activity of the locus coeruleus-central
      adrenergic system that increases the signal-to-noise ratio and improves the
      brain's ability to attend to sensory input, but decreases its ability to recruit
      large-scale networks.

PMID- 16647303
TI  - Cdo functions at multiple points in the Sonic Hedgehog pathway, and Cdo-deficient
      mice accurately model human holoprosencephaly.
AB  - Holoprosencephaly (HPE), a common defect of human forebrain development, is
      associated with haploinsufficiency for genes encoding Sonic Hedgehog (SHH)
      pathway components. Clinical expression of HPE is extremely variable, but it is
      rarely associated with defects in other SHH-dependent structures, such as limbs.
      Here we report that mice lacking the transmembrane protein Cdo, previously
      implicated in myogenesis, display HPE with strain-specific severity and without
      limb defects, modeling human HPE and implicating modifier genes as a cause of
      variability. Shh target gene expression is reduced in the developing forebrains
      of Cdo-/- mice, and Cdo positively regulates Shh signaling in vitro. Our data
      suggest that Cdo enhances pathway activity in multiple ways, including at signal
      reception and via a parallel mechanism required at the level of Gli transcription
      factors. Specific Cdo domains required for its promyogenic effect are dispensable
      for its Shh signaling role, suggesting that Cdo has multiple, independent
      functions.

PMID- 16647304
TI  - The cell surface membrane proteins Cdo and Boc are components and targets of the
      Hedgehog signaling pathway and feedback network in mice.
AB  - Cdo and Boc encode cell surface Ig/fibronectin superfamily members linked to
      muscle differentiation. Data here indicate they are also targets and signaling
      components of the Sonic hedgehog (Shh) pathway. Although Cdo and Boc are
      generally negatively regulated by Hedgehog (HH) signaling, in the neural tube Cdo
      is expressed within the Shh-dependent floor plate while Boc expression lies
      within the dorsal limit of Shh signaling. Loss of Cdo results in a Shh dosage
      dependent reduction of the floor plate. In contrast, ectopic expression of Boc or
      Cdo results in a Shh-dependent, cell autonomous promotion of ventral cell fates
      and a non-cell-autonomous ventral expansion of dorsal cell identities consistent
      with Shh sequestration. Cdo and Boc bind Shh through a high-affinity interaction
      with a specific fibronectin repeat that is essential for activity. We propose a
      model where Cdo and Boc enhance Shh signaling within its target field.

PMID- 16647305
TI  - Perspectives on integration of cell extrinsic and cell intrinsic pathways of
      signaling required for differentiation of noradrenergic sympathetic ganglion
      neurons.
AB  - This review presents an analysis of current research aimed at deciphering the
      interplay of cell extrinsic and intrinsic signals required for specification and
      differentiation of noradrenergic sympathetic ganglion neurons. The development of
      noradrenergic sympathetic ganglion neurons depends upon expression of a core set
      of DNA regulatory molecules, including the Phox2 homeodomain proteins and the
      basic helix-loop-helix proteins, HAND2 and MASH1 whose expression is dependent
      upon cell extrinsic cues. Both bone morphogenetic protein(s) and cAMP have an
      integral role in the specification/differentiation of noradrenergic sympathetic
      ganglion neurons but how signaling downstream of these molecules is integrated
      and identification of their particular functions is just beginning to be
      elucidated. Data currently available suggests a model with BMP providing both
      instructive and permissive cues in a pathway integrated by cAMP and MAPK by
      activation of both canonical and non-canonical intracellular signaling cascades.

PMID- 16647306
TI  - Regulation of the slow afterhyperpolarization in enteric neurons by protein
      kinase A.
AB  - The slow after-hyperpolarization (sAHP) following the action potential is an
      important determinant of the firing patterns of enteric neurons. The channel
      responsible for the sAHP thus serves as a critical control point at which
      neurotransmitters and inflammatory mediators modulate gut motility. Many of these
      receptor-evoked pathways are known to inhibit the sAHP and, thus, excite enteric
      neurons. They act through protein kinase A (PKA) which is a strong inhibitor of
      the sAHP current while protein phosphatases enhance the current. Increasing
      evidence suggests that the sAHP is mediated by the opening of intermediate
      conductance Ca-activated potassium (IK) channels. This neuronal IK channel,
      previously known to be expressed in a variety of non-excitable cells, is strongly
      influenced by protein kinases. Investigation of the molecular basis for the
      modulation of IK channels by protein phosphorylation indicates that there are
      multiple mechanisms of channel control. Inhibition of channel activity by PKA
      involves phosphorylation sites located within the calmodulin-binding domain of
      the channel. The localization of these sites within the region involved in Ca2+
      activation suggests that PKA-mediated phosphorylation of the channel opposes the
      conformational changes caused by binding of Ca/calmodulin, which would otherwise
      lead to opening of the channel. We suggest that the channel exists as a
      macromolecular complex involving calmodulin, protein kinases, protein phosphatase
      and possibly other proteins. The regulation of the channel through kinases and
      phophatases results in exquisite control of neuronal firing and subsequent
      modulation of enteric reflexes.

PMID- 16647307
TI  - Effect of the malaria vaccine Combination B on merozoite surface antigen 2
      diversity.
AB  - Extensive genetic polymorphism is generally found in Plasmodium falciparum
      surface antigens. This poses a considerable obstacle to the development of a
      malaria vaccine. In order to assess possible effects of a polymorphic vaccine, we
      have analyzed the genetic diversity of parasites collected in the course of a
      phase 2b field trial of the blood stage vaccine Combination B in Papua New
      Guinea. The full-length 3D7 allele of the merozoite surface protein 2 (MSP2) was
      included in Combination B as one of three subunits. Vaccinees had a lower
      prevalence of parasites carrying a 3D7-type allele (corresponding to that in the
      vaccine) and selection appeared to favour the alternative FC27-type alleles
      resulting in a higher incidence of morbid episodes associated with FC27-type
      parasites. We sequenced MSP2 alleles detected in study participants after
      vaccination to identify breakthrough genotypes. Extensive genetic diversity of
      MSP2 was observed in both the repetitive and family-specific domains, but alleles
      occurring in vaccine recipients were no different from those found in placebo
      recipients. A phylogenetic analysis showed no clustering of 3D7-type breakthrough
      infections from vaccine recipients. The repeat unit present in the vaccine
      molecule occurred in a number of alleles from the trial area and was also
      observed in vaccinated individuals. Thus the anti-repeat immune response did not
      lead to elimination of parasites carrying the same repeat unit. We conclude that
      the conserved epitopes in the family-specific domain were the most important
      determinants of the vaccine effect against new 3D7-type infections and that the
      hypervariable domains were not subject to selective effects of the vaccine.

PMID- 16647308
TI  - Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle.
AB  - Locomotor functional decline and loss in muscle mass with age is virtually a
      universal characteristic that has been documented in several species, including
      worms, fruit flies, rodents, non-human primates and humans. The age-related loss
      of muscle mass and strength (sarcopenia) represents an important risk factor for
      disability and mortality in older subjects and has been linked with cellular
      energy deficit and increased apoptosis at old age. Many key theories on aging
      describing the mechanisms underlying sarcopenia are now focused on the
      mitochondria because of their dichotomous role in controlling life and death
      processes within myocytes. Mitochondria represent the main producers of cellular
      energy in the form of adenosine triphosphate, but are also considered a key
      regulatory center of apoptosis. Unknown factors leading to a decrease in aerobic
      energy efficiency are linked with mitochondrial mutations which may result into
      apoptosis. Moreover, deregulation of autophagy (degradation and recycling of long
      lived protein and organelles, such as the mitochondria) in post-mitotic tissue
      might also be responsible for the age-associated cellular energy failure.
      Alterations in specific signaling pathways, such as AMP-activated protein
      kinases, play a role in both cell survival response and apoptotic response
      depending on energy depletion. Evidence supports that apoptosis occurring in
      aging skeletal muscle may be due, in part, to the progressive decline in
      mitochondrial function and the resulting energy depletion within the cell. In
      turn, mitochondrial dysfunction is partly due to the accumulation of oxidative
      damage to macromolecules, including mitochondrial DNA, RNA and proteins,
      essential components for optimal functioning of mitochondria. Evidence concerning
      these series of events leading to energy depletion and apoptosis are discussed.

PMID- 16647309
TI  - Isolation and characterization of cotiaractivase, a novel low molecular weight
      prothrombin activator from the venom of Bothrops cotiara.
AB  - In this study, we isolated a novel prothrombin activator from the venom of
      Bothrops cotiara, a Brazilian lance-headed pit viper (Cotiara, Jararaca preta,
      Biocotiara), which we have designated "cotiaractivase" (prefix: cotiar- from B.
      cotiara; suffix: -activase, from prothrombin activating activity). Cotiaractivase
      was purified using a phenyl-Superose hydrophobic interaction column followed by a
      Mono-Q anion exchange column. It is a single-chain polypeptide with a molecular
      weight of 22,931 Da as measured by mass spectroscopy. Cotiaractivase generated
      active alpha-thrombin from purified human prothrombin in a Ca2+-dependent manner
      as assessed by S2238 chromogenic substrate assay and SDS-PAGE. Cotiaractivase
      cleaved prothrombin at positions Arg271-Thr272 and Arg320-Ile321, which are also
      cleaved by factor Xa. However, the rate of thrombin generation by cotiaractivase
      was approximately 60-fold less than factor Xa alone and 17 x 10(6)-fold less than
      the prothrombinase complex. The enzymatic activity of cotiaractivase was
      inhibited by the chelating agent EDTA, whereas the serine protease inhibitor PMSF
      had no effect on its activity, suggesting that it is a metalloproteinase.
      Interestingly, S2238 inhibited cotiaractivase activity non-competitively,
      suggesting that this toxin contains an exosite that allows it to bind prothrombin
      independently of its active site. Tandem mass spectrometry and N-terminal
      sequencing of purified cotiaractivase identified peptides that were identical to
      regions of the cysteine-rich and disintegrin-like domains of known snake venom
      metalloproteinases. Cotiaractivase is a unique low molecular weight snake venom
      prothrombin activator that likely belongs to the metalloproteinase family of
      proteins.

PMID- 16647310
TI  - Pain assessment: current status and challenges.
AB  - Neonatal pain assessment has received much attention over the past decade.
      Behavioural indicators of pain include facial action, body movement and tone,
      cry, state/sleep, and consolability. Physiological indicators of pain include
      increased heart rate, respiratory rate, and blood pressure, as well as decreased
      heart rate variability and oxygen desaturation. Pain assessment in neonates is
      difficult in neurologically compromised, chemically paralyzed, and non-responsive
      infants. Multiple pain assessment tools are summarized. Pain assessment and
      management protocols are delineated.

PMID- 16647311
TI  - Promoting the value of early nutritional intervention.

PMID- 16647312
TI  - Improving bone health.

PMID- 16647313
TI  - See ourselves as others see us: appreciate your excellence.

PMID- 16647315
TI  - Making MyPyramid for kids a successful tool in nutrition education.

PMID- 16647316
TI  - Promote yourself and your profession with sound bites.

PMID- 16647317
TI  - Healthy America--the opportunity to meet the challenge in our states.

PMID- 16647318
TI  - Confirmation of the cereal type in oat products highly contaminated with gluten.

PMID- 16647320
TI  - Weight-control practices as potential confounding variable.

PMID- 16647321
TI  - Foods that the Lewis and Clark expedition ate in Idaho.

PMID- 16647323
TI  - Prevention and treatment of the metabolic syndrome with lifestyle intervention:
      where do we start?

PMID- 16647324
TI  - Cardiorespiratory fitness, macronutrient intake, and the metabolic syndrome: the
      Aerobics Center Longitudinal Study.
AB  - OBJECTIVE: This study examines the cross-sectional associations between
      cardiorespiratory fitness and the metabolic syndrome with adjustment for
      macronutrient intake from 3-day dietary records. DESIGN: Cross-sectional study.
      SUBJECTS/SETTING: Women and men who had a comprehensive medical examination,
      including a symptom-limited maximal treadmill exercise test, and completed 3-day
      dietary records at the Cooper Clinic, Dallas, TX. MAIN OUTCOME MEASURES:
      Metabolic syndrome as defined by the National Cholesterol Education Program Adult
      Treatment Panel III criteria. STATISTICAL ANALYSES PERFORMED: Analysis of
      variance was used to examine differences in continuous data. General linear
      analysis was used to examine linear trends. Mantel-Haenszel chi(2) analyses were
      used to examine differences in categorical data. Logistic regression was used to
      estimate odds ratios and 95% confidence intervals. RESULTS: After adjusting for
      sex and age, cardiorespiratory fitness was inversely associated with the
      prevalence of metabolic syndrome (P<0.001). Adjustment for macronutrient intake
      and other potential confounding variables did not alter the association between
      cardiorespiratory fitness and prevalent metabolic syndrome. CONCLUSIONS:
      Cardiorespiratory fitness is inversely associated with the prevalence of
      metabolic syndrome. Patients should be encouraged to increase their physical
      activity to decrease their risk for metabolic syndrome and coronary heart
      disease.

PMID- 16647325
TI  - Serum iron and body fat distribution in a multiethnic cohort of adults living in
      New York City.
AB  - OBJECTIVE: To examine the relationship between serum iron and body composition in
      a multiracial adult cohort. METHODS: The analysis consisted of 670 participants
      on whom blood analysis and anthropometric data were available. The participants
      were recruited as part of the Rosetta Study (1990-2000), which was designed to
      assess body composition in a multiethnic cohort of healthy adults. Fasting iron
      level was measured as part of a biochemistry panel. Dual x-ray absorptiometry was
      used to assess fat mass. Anthropometric measures included waist circumference and
      body mass index (BMI; calculated as kg/m(2)) as an index of abdominal adiposity
      and overall body fatness, respectively. RESULTS: In the study cohort the mean age
      was 54+/-17 years and 60.9% were overweight or obese (BMI > or =25). Men had
      higher serum iron levels (94.91+/-34.52 microg/dL [16.99+/-6.18 micromol/L] vs
      82.17+/-32.62 microg/dL [14.71+/-5.84 micromol/L]) and larger waist circumference
      (91.98+/-11.87 cm vs 85.24+/-12.37 cm) compared with women (P<0.001). Iron was
      inversely correlated with BMI (r=-0.23, P<0.001), waist circumference (r=-0.19,
      P<0.05), and fat mass (r=-0.19, P<0.05) among Hispanic women but not among
      African-American, white, or Asian women or in men of any race/ethnic group.
      CONCLUSIONS: The results of this study show an inverse association of measures of
      body fat distribution and total fat mass with serum iron level in Hispanic women.
      Studies designed to explore how micronutrients are used by the body at varying
      degrees of body fatness could provide useful information on the micronutrient
      related comorbidities of obesity.

PMID- 16647326
TI  - Dietary intake among youth with diabetes: the SEARCH for Diabetes in Youth Study.
AB  - OBJECTIVE: To describe dietary intake among a large cohort of youth with type 1
      or type 2 diabetes and to compare their intake with current nutrition
      recommendations. DESIGN: SEARCH for Diabetes in Youth is a multicenter study of
      diabetes in youth. Diet was assessed among youth aged 10 to 22 years who attended
      a SEARCH research clinic visit and completed a previous-week food frequency
      questionnaire that included foods to reflect the ethnic and regional diversity
      represented by the cohort. SUBJECTS/SETTING: Included were 1,697 youth with
      physician-diagnosed diabetes mellitus (89% type 1 diabetes, 11% type 2 diabetes),
      with diabetes mellitus duration of at least 12 months. STATISTICAL ANALYSES:
      Descriptive data and comparisons with nutrition recommendations were unadjusted.
      Analyses of covariance with adjustment for total energy, clinic site, sex,
      race/ethnicity, age, and parental education were used to compare intake according
      to diabetes type. RESULTS: Percent of energy from total fat was consistent at 37%
      to 38% across subgroups of age (10 to 14 years, >15 years) and diabetes type (ie,
      type 1 or type 2). Youth with type 2 diabetes consumed less calcium, magnesium,
      and vitamin E than youth with type 1 diabetes (P<0.01 for each). Intake of
      sweetened carbonated beverages among older (aged >15 years) youth with type 2
      diabetes was twice that of older youth with type 1 diabetes (P<0.01). Only 6.5%
      of the cohort met American Diabetes Association recommendations of <10% of energy
      from saturated fat. Less than 50% met recommendations for total fat, vitamin E,
      fiber, fruits, vegetables, and grains, although a majority met recommendations
      for vitamin C, calcium, and iron. CONCLUSIONS: Overall, dietary intake in this
      large cohort of youth with diabetes substantially failed to meet current
      recommendations. There is a critical need for improvement in dietary intake in
      youth with diabetes.

PMID- 16647327
TI  - Psychological predictors of physical activity in the diabetes prevention program.
AB  - OBJECTIVE: To identify the baseline psychological variables before receiving a
      Diabetes Prevention Program (DPP) lifestyle intervention that predict physical
      activity levels (PALs) at baseline, 1 year, and end of study (2 to 3 years after
      randomization). DESIGN AND SUBJECTS: Of the final 293 DPP lifestyle participants
      randomized, 274 (94%) completed validated questionnaires at baseline assessing
      stage of change for PAL, exercise self-efficacy, perceived stress, depression,
      and anxiety. STATISTICAL ANALYSES PERFORMED: Correlations and stepwise multiple
      regression analyses. RESULTS: At baseline, this subset was similar to the entire
      DPP lifestyle cohort: mean age was 52.5 years, 65% were women, and mean PAL was
      15.7 metabolic equivalent hours per week. Higher levels of baseline leisure PAL
      correlated with greater readiness to change PAL (r=0.44, P<0.0001), higher
      exercise self-efficacy (r=0.18, P=0.002), and lower levels of perceived stress
      (r=-0.16, P=0.009), depression (r=-0.18, P=0.003), and anxiety (r=-0.14, P=0.03),
      with similar correlations at 1 year and end of study. In multivariate models,
      being a man, lower levels of depression, and lower body mass index were
      independent correlates of higher baseline leisure PAL; being a man, greater
      baseline exercise self-efficacy, and activity level were independent correlates
      of greater leisure PAL levels at 1 year and end of study. Greater readiness to
      change PAL at baseline was also an independent correlate of greater PAL at end of
      study. CONCLUSIONS: In this representative sample of DPP lifestyle participants,
      being a man, lower body mass index, greater readiness for change in PAL, higher
      exercise self-efficacy, and lower perceived stress, depression, and anxiety
      scores correlated with higher levels of baseline PAL with similar patterns at 1
      year and end of study. These findings may help determine which patients are most
      likely to increase PAL in lifestyle intervention programs.

PMID- 16647328
TI  - Diabetes prevention program strategies and tools could be translated to practice
      setting.

PMID- 16647329
TI  - Adolescents involved in weight-related and power team sports have better eating
      patterns and nutrient intakes than non-sport-involved adolescents.
AB  - OBJECTIVE: To examine eating habits and energy and nutrient intake among
      adolescents participating in weight-related and power team sports and non-sport
      involved adolescents. DESIGN: Data were drawn from Project EAT (Eating Among
      Teens), which was conducted with 4,746 adolescents from 31 middle and high
      schools in the Minneapolis/St Paul metropolitan area. SETTING: Urban secondary
      schools. SUBJECTS: Adolescents reporting participation in a weight-related sport,
      a power team sport, or no consistent participation in a sport. MAIN OUTCOME
      MEASURES: Meal and snack frequency, mean energy and nutrient intake, and mean
      physical activity. STATISTICAL ANALYSES PERFORMED: Analyses were conducted by sex
      across the three groups. General linear models were used to compare mean energy
      and nutrient intake, composite nutrient adequacy, and mean physical activity
      across the three groups. Percentages of youth meeting nutrient recommendations
      were compared across the three groups using chi(2) tests. RESULTS: For both males
      and females, youth involved in weight-related sports ate breakfast more
      frequently than non-sport-involved peers (females: 3.6 and 3.2 times per week,
      respectively, P<0.01; males: 4.7 and 3.7 times per week, respectively, P<0.01).
      Weight-related and power team sport-involved youth also had higher mean protein,
      calcium, iron, and zinc intakes than non-sport-involved peers. However,
      adolescent females had low calcium intake, regardless of sports involvement
      (weight-related sports 1,091 mg/day, power team sports 1,070 mg/day, and non
      sport-involved 1,028 mg/day, P<0.05). CONCLUSIONS: Sport-involved adolescents
      have better eating habits and nutrient intake than their non-sport-involved
      peers. However, they are still in need of nutrition interventions, particularly
      around calcium intake.

PMID- 16647330
TI  - Dietary intake of adolescent athletes and nonathletes.

PMID- 16647331
TI  - Use of a risk communication model to evaluate dietetics professionals' viewpoints
      on genetically engineered foods and crops.
AB  - The complex issues surrounding the application of genetic engineering to food and
      agriculture have generated a contentious debate among diverse interest groups.
      One pervasive dimension in the resultant discourse is the varying perceptions of
      the risks and benefits of genetically engineered foods and crops. In the risk
      communication model, technical information is evaluated within the context of an
      individual's values and perceptions. The purpose of this study was to explore how
      dietetics professionals respond to a complex set of interrelated issues
      associated with genetically engineered foods and crops and to identify what
      varying viewpoints may exist. Participants were asked to sort a total of 48
      statements distributed across eight issue areas according to level of agreement
      and disagreement. Using Q methodology, a total of 256 sortings were analyzed
      using the centroid method and varimax rotation in factor analysis. Three distinct
      viewpoints emerged: Precautionary (R(2)=43%), Discerning Supporter (R(2)=11%),
      and Promoting (R(2)=5%). Across all viewpoints, respondents agreed that dietetics
      professionals should employ critical thinking skills to communicate the social,
      economic, environmental, ethical, and technical aspects of genetically engineered
      foods and crops. The findings have implications for how dietetics professionals
      can foster an open interchange of information among diverse groups.

PMID- 16647332
TI  - Dietary glycemic index of human immunodeficiency virus-positive men with and
      without fat deposition.
AB  - This study focused on dietary glycemic index because insulin resistance can be
      important in the pathogenesis of fat deposition in human immunodeficiency virus
      (HIV). We evaluated differences in past dietary glycemic intake between men with
      HIV who developed fat deposition and those who did not. This was a nested case
      control study consisting of 37 cases and 37 controls from the Nutrition for
      Healthy Living cohort. Food records from 6 to 24 months prior to development of
      fat deposition in cases were analyzed and compared with controls. Cases were
      defined as men with a waist-to-hip ratio >0.95 and body mass index (calculated as
      kg/m(2)) between 23 and 26. Controls were matched by age, race, body mass index,
      highly active antiretroviral therapy use, and CD4 count. Food records were
      analyzed using t tests for normally distributed nutrients and Wilcoxon rank-sum
      tests for nutrients with skewed distributions. Glycemic index was calculated for
      each meal and day. There was no significant difference in glycemic index for
      meals and day between participants with or without fat deposition. Both groups
      had a moderate dietary glycemic index intake. This study showed no association
      between dietary glycemic index and development of fat deposition in HIV. Instead,
      results of this study depict the potential benefits associated with eating high
      quality diets, primarily adequate fiber and protein intake. Diet can be important
      in preventing development of fat deposition in patients with HIV.

PMID- 16647333
TI  - Using dietary reference intake-based methods to estimate prevalence of inadequate
      nutrient intake among female students in Brazil.
AB  - The objective of this study was to estimate the prevalence of inadequate usual
      nutrient intake among female university students. This was a cross-sectional
      study in which 119 students at a public university in the State of Sao Paulo,
      Brazil, completed 3-day estimated food records. These were analyzed for nutrient
      content, and intake distributions were determined. Nutrient intake distributions
      were estimated using the National Research Council method. For nutrients for
      which an Estimated Average Requirement has been established, the Estimated
      Average Requirement cutpoint method was used to determine the proportion of
      students with inadequate intake. The students' food records indicated inadequate
      intakes of folate (99%), zinc (47%), and copper (33%). For approximately 95% of
      the students in this study, calcium was less than the Adequate Intake. The
      results showed the need for improvement in dietary choices to minimize the
      prevalence of inadequate intake of folate, zinc, copper, and calcium in this
      group.

PMID- 16647334
TI  - A comparison of two methods of measuring food group intake: grams vs servings.
AB  - Different measurements can be used to quantify food group intake, such as
      servings, cups, or grams. Dietary recommendations are given in terms of servings
      (recently expressed as cup and ounce measurements), but research on disease risks
      often uses grams as the intake measure. Because serving sizes vary among foods
      within a food group, the method of expressing food group intake (grams vs
      servings) may impact disease risk analyses. Daily consumption of eight food
      groups was calculated as both Food Guide Pyramid servings and grams for 206,721
      participants in the Multiethnic Cohort Study who completed a quantitative food
      frequency questionnaire between 1993 and 1996. Mean grams per serving ranged from
      25 g for red meat to 172 g for dairy products. Spearman correlation coefficients
      between intakes as grams per day and servings per day were 0.85 for grains, 0.97
      for vegetables, 0.99 for fruit, 0.95 for dairy products, 0.98 for red meat, 0.93
      for processed meat, 1.00 for poultry, and 1.00 for fish. Because there was little
      effect on the ranking of study participants' intakes due to the method of
      calculating food group consumption, the two measures are interchangeable in
      disease risk models.

PMID- 16647335
TI  - Choices made by low-income women provided with an economic supplement for fresh
      fruit and vegetable purchase.
AB  - Vouchers for fresh fruit and vegetable purchase were provided to low-income women
      participating in the Special Supplemental Nutrition Program for Women, Infants,
      and Children (WIC) in Los Angeles, CA. As the program is currently constituted,
      the supplemental foods provided contain no fresh produce except for carrots for
      exclusively breastfeeding women. This study investigated whether providing
      supplemental financial support specifically for purchase of fresh fruits and
      vegetables would result in high uptake of the supplement, and what the
      individuals would choose to purchase. A total of 602 women enrolling for
      postpartum services at three selected WIC program sites in Los Angeles were
      recruited. Sites were assigned to intervention with vouchers redeemable at a
      local supermarket, a nearby year-round farmers' market, and a control site with a
      minimal nonfood incentive. Vouchers were issued bimonthly, at the level of US
      $10/wk, and carried out for 6 months. Of 454 participants who completed the study
      (75.4%), 86% were Hispanic, 7% non-Hispanic black, and 7% of other ethnic
      backgrounds. Assessment of uptake was by voucher redemption rates and was
      approximately 90% for both groups. Participants reported purchasing a wide
      variety of items at both sites. The 10 most frequently mentioned items were
      oranges, apples, bananas, peaches, grapes, tomatoes, carrots, lettuce, broccoli,
      and potatoes. In conclusion, low-income women used the supplement provided almost
      fully, and purchased a wide variety of fresh fruits and vegetables for their
      families. No particular barriers arose to redemption of the vouchers by either
      the participants or the retail vendors.

PMID- 16647336
TI  - The effect of three snack bars on glycemic response in healthy adults.
AB  - Many consumers prefer convenient, portable, and preportioned snack foods. Foods
      with a lower glycemic response are associated with reduced risk for chronic
      disease. The glycemic index and glycemic load of three nationally available snack
      bars were determined. Ten subjects, with mean age (+/-standard deviation) of 29+/
      7 years and mean body mass index (+/-standard deviation) of 25.3+/-3.2, were
      tested on four occasions on nonconsecutive days. After an overnight fast,
      subjects consumed 50 g of available carbohydrate as a glucose beverage or as a
      portion of one of three bars: SmartZone nutrition bar (The Hershey Co, Hershey,
      PA), ZonePerfect nutrition bar (Abbott Laboratories, Abbott Park, IL), or
      SlimFast meal bar (SlimFast Foods Co, West Palm Beach, FL). Blood glucose was
      tested at 0, 15, 30, 45, 60, 90, and 120 minutes after consumption. Incremental
      area under the glucose response curve was calculated for each test bar and
      compared with that of the glucose beverage to determine glycemic index. The
      glycemic index (+/-standard error of the mean) for SmartZone was 10.9+/-3.9 and
      was significantly less (P<0.05) than that of ZonePerfect (43.7+/-7.3) or SlimFast
      (63.8+/-13.0). The glycemic loads (+/-standard error of the mean) for the
      SmartZone (2.0+/-0.7) and ZonePerfect (8.3+/-1.4) bars were significantly less
      (P<0.05) than the glycemic load of the SlimFast bar (21.1+/-4.3). Although the
      long-term impact of snack foods with a lower glycemic load requires further
      research, the SmartZone and ZonePerfect bars provide a lower glycemic response
      for consumers.

PMID- 16647337
TI  - Where can I find resources to address healthful weight practices for wrestlers?

PMID- 16647338
TI  - Teaching a legacy.

PMID- 16647339
TI  - Dr. Oswald Meredith Jones, a talented and gallant Welshman.

PMID- 16647340
TI  - Transgenic introduction of androgen receptor into estrogen-receptor-,
      progesterone-receptor-, and androgen-receptor-negative breast cancer cells
      renders them responsive to hormonal manipulation.
AB  - BACKGROUND: Estrogen-receptor (ER)-, progesterone-receptor (PR)-, and androgen
      receptor (AR)-negative breast cancer cells are unaffected by treatment with
      dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We
      hypothesized that cell growth would be inhibited with DHEAS/AI treatment after
      successful transfection of an AR expression vector. METHODS: ER/PR/AR-negative
      breast cancer cells were transfected with an AR expression vector and treated
      with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that
      of transfected cells treated with only AI or with nontransfected cells treated
      with DHEAS/AI. Mann-Whitney U test was used to determine statistical
      significance. RESULTS: Cell death rates of 53.5% (P = .001) and 40.1% (P = .006)
      were seen in transfected cells treated with DHEAS/AI compared with controls for
      days 1 and 2, respectively. Nontransfected cells were unaffected by treatment.
      COMMENTS: ER/PR/AR-negative cells transfected with AR were killed by DHEAS/AI
      treatment, providing evidence that AR is responsible for this effect. This
      provides the first AR-targeted hormonal therapy for ER breast cancer.

PMID- 16647341
TI  - Derangement of the E-cadherin/catenin complex is involved in transformation of
      differentiated to anaplastic thyroid carcinoma.
AB  - BACKGROUND: Anaplastic thyroid cancer arises, or transforms, from pre-existing
      differentiated thyroid cancer. E-cadherin functions as a cell-cell adhesion
      molecule that complexes with catenin proteins for function. The objective of this
      study was to evaluate the change in E-cadherin/beta-catenin expression in the
      transformation of differentiated to anaplastic thyroid carcinoma. METHODS: A
      tissue microarray was constructed from 12 anaplastic thyroid tumors and their
      adjacent associated differentiated foci. Immunohistochemistry was used to
      evaluate tumor expression of E-cadherin and beta-catenin. RESULTS: There was
      decreased expression of E-cadherin and beta-catenin by the anaplastic tumors when
      compared with the differentiated thyroid tumors from which they evolved. The
      expression of E-cadherin and beta-catenin was 92% and 67%, respectively, by the
      differentiated thyroid carcinoma, and 17% and 50%, respectively, by the
      anaplastic tumors. CONCLUSIONS: This report shows that derangement of the E
      cadherin/catenin complex is associated with the transformation of differentiated
      into anaplastic thyroid carcinoma.

PMID- 16647342
TI  - Glutathione depletion of stimulator cells inhibits responder T-cell
      immunogenicity in vitro and prolongs allograft survival in vivo.
AB  - BACKGROUND: Pretransplant donor-organ immunomodulation may attenuate allograft
      rejection by changing the redox state of donor cells. This study explored impact
      of donor-cell redox-state alteration by glutathione (GSH) depletion on graft
      immunogenicity. METHODS: Splenic and heart endothelial cells from Balb/c mice
      were treated with diethylmaleate (a GSH-depleting agent) and/or
      lipopolysaccharide to assess the impact of GSH depletion on alloreactivity by
      mixed lymphocyte reaction, endothelial cell adhesion by T-cell adhesion assay,
      intracellular adhesion molecule-1 expression by reverse transcriptionase
      polymerase chain reaction, and nuclear factor-kappa B upregulation by
      electrophoretic mobility shift assay. Heterotopic heart transplants were
      performed as in vivo correlate. RESULTS: GSH depletion decreased endothelial cell
      and splenic cell alloreactivity, decreased endothelial cell intracellular
      adhesion molecule-1 expression through attenuation of nuclear factor-kappa B
      activity, decreased endothelial cell adhesion, and prolonged heterotopic heart
      transplant graft survival. CONCLUSIONS: GSH depletion may represent a significant
      immunomodulator of donor antigenicity to prevent transplant rejection.

PMID- 16647343
TI  - Hemithyroidectomy: the preferred initial surgical approach for management of
      Hurthle cell neoplasm.
AB  - BACKGROUND: The objective of this study was to evaluate the cancer risk of
      patient clinicopathologic characteristics to determine the optimal approach for
      the surgical management of individuals with Hurthle cell neoplasm (HN) diagnosed
      by cytology. METHODS: Patient clinicopathologic characteristics evaluated
      included age, sex, tumor size, and ipsilateral thyroid lobe nodularity. The
      association of these characteristics with a pathologic cancer diagnosis was
      evaluated using Fisher's exact test and Student t test. RESULTS: Of the 422
      patients undergoing thyroidectomy, 27 presented with a fine-needle aspiration
      biopsy diagnosis of HN, and by pathologic assessment 7 HN patients (25.9%) had a
      cancer diagnosis. Although none of the clinicopathologic characteristics
      evaluated were able to reliably differentiate benign from malignant tumors, large
      tumor size and male sex were significantly associated with a pathologic diagnosis
      of Hurthle cell carcinoma (P < .05). CONCLUSIONS: Hemithyroidectomy represents
      the preferred initial surgical approach for the management of individuals
      presenting with nodular thyroid disease and a cytologic diagnosis of HN.

PMID- 16647344
TI  - Complex hepatic surgery aided by a 1.5-tesla moveable magnetic resonance imaging
      system.
AB  - BACKGROUND: Resection represents the best treatment for potentially curable liver
      tumors; radiofrequency ablation (RFA) is an alternative. The curative potential
      of RFA may be hampered because the extent of burn is difficult to estimate by
      ultrasound. We postulated that intraoperative MRI (iMRI) would enable a more
      accurate assessment of ablation completeness. METHODS: We performed open hepatic
      surgery in an operating room equipped with a unique, retractable 1.5-T magnet.
      Patients were selected because it was anticipated that RFA (with or instead of
      resection) was likelihood and that iMRI might be helpful in making intraoperative
      decisions. After baseline MRI, lesions were further assessed by ultrasound at the
      time of open surgery. Lesions were resected and/or ablated, and further imaging
      confirmed the margins of the procedure. RESULTS: Nine patients underwent the
      procedure: 1 with metastatic carcinoid, 4 with hepatocellular carcinoma, and 4
      with colorectal liver metastases. In 4 patients, iMRI had an effect on decision
      making. In 5 individuals, there were nonlocal recurrences, and 1 patient who was
      never disease-free had a local recurrence. COMMENTS: Intraoperative MRI could
      potentially impact operative decision-making when ablating extensive disease. Its
      ability to prevent local recurrences must be determined. Moreover, the role of
      this technology in the overall treatment armamentarium must be defined.

PMID- 16647345
TI  - The use of damage-control principles for penetrating pelvic battlefield trauma.
AB  - BACKGROUND: High-velocity, penetrating pelvic injuries present one of the most
      difficult challenges to military trauma surgeons. The patients often present in
      physiologic extremis, and their injury-site patterns frequently include soft
      tissue, pelvic fractures, genitourinary tract, rectum, vascular structures, and
      intra-abdominal viscera. METHODS: A retrospective review of the 31st Combat
      Support Hospital damage-control laparotomy database, under an Institutional
      Review Board-approved protocol, revealed 28 patients with severe multisystem
      penetrating pelvic injuries. Up to 75 data points were queried for each patient
      and subjected to descriptive analysis using SPSS 11.0.4 Statistical Software
      Package (SPSS, Inc, Chicago, IL). RESULTS: Of 28 patients with severe penetrating
      pelvic injuries, 43% had extraperitoneal rectal, 43% had urologic, and 50% had
      major vascular injuries. On average, patients required 4 abdominal operations for
      treatment of all injuries. Six of 28 (21%) patients died within the first week
      after injury, and 36% of patients with vascular and rectal injuries died.
      CONCLUSIONS: Management of these injuries frequently required damage-control
      techniques and a staged, multidisciplinary approach to reconstruction. Combined
      rectal and vascular injuries were the most devastating in this type of injury
      complex.

PMID- 16647346
TI  - The impact of hypothermia on trauma care at the 31st combat support hospital.
AB  - BACKGROUND: The primary objective of this study was to review the incidence of
      hypothermia, and its effect on surgical management, resource utilization, and
      survival at the 31st Combat Support Hospital (CSH). METHODS: This study was a
      retrospective analysis of all combat trauma injuries treated at the 31st CSH over
      a 12-month period. All trauma admissions were included. Descriptive and
      inferential analysis were performed using SPSS 11.0 software package (SPSS Inc.,
      Chicago, IL). RESULTS: A cohort of 2848 patients was identified; 18% were
      hypothermic (temperature < 36 degrees C). Hypothermia was significantly (P < .05)
      correlated with admission Glasgow Coma Scale (GCS), tachycardia, hypotension,
      lower hematocrit, and acidosis. Hypothermic patients had a significantly higher
      blood product and factor VIIa requirement. Hypothermia was an independent
      predictor of operative management of injuries, damage control laparotomy, factor
      VIIa use, and overall mortality (P < .05). CONCLUSION: Combat trauma patients
      have a high percentage of penetrating injuries with variable evacuation times.
      Hypothermia was a pre-hospital physiologic marker, and independent contributor to
      overall mortality. Prevention of hypothermia could reduce resource utilization
      and improve survival in the combat setting.

PMID- 16647347
TI  - Population-based analysis of severe injuries from nonmotorized wheeled vehicles.
AB  - BACKGROUND: Bicycling, skateboarding, and inline skating are popular recreational
      activities, with the potential of causing severe injury. METHODS: A
      retrospective, population-based, trauma registry analysis of severe injuries and
      deaths from nonmotorized wheeled vehicles (NMWV) over a 10-year period was
      performed. RESULTS: During the study period, 1475 cyclists, 141 skateboarders,
      and 112 inline skaters sustained injury meeting registry criteria (length of stay
      > or = 3 days or death). The majority were male. Lone crashes were the most
      common mechanism of injury, although collisions with motor vehicles accounted for
      63.6% (n = 44) of observed deaths. Thoracic trauma and head injuries were more
      common in nonsurvivors. CONCLUSION: NMWV injuries pose a public health concern.
      We recommend enforcement of mandatory helmet laws and expansion of the existing
      law to include skateboarders and inline skaters. Education initiatives should
      also be expanded to include the adult population. NMWV should be separated from
      motorized vehicles as much as possible.

PMID- 16647348
TI  - Renal allograft compartment syndrome: an underappreciated postoperative
      complication.
AB  - PURPOSE: Renal allograft compartment syndrome (RACS) is early graft dysfunction
      secondary to retroperitoneal hypertension and resultant ischemia. Our purpose was
      to identify the incidence, therapies and outcomes of patients with RACS. METHODS:
      All patients who underwent a renal transplant between 2000 and 2005 were
      reviewed. Patients with signs of acute allograft dysfunction were identified.
      RACS was diagnosed via visual allograft hypoperfusion and/or with preoperative
      Doppler ultrasound. RESULTS: Among 458 patients, 11 (2%) were diagnosed with
      RACS. Characteristics between patient groups were similar. Five (45%) patients
      displayed adequate initial allograft function after transplantation. Doppler
      ultrasound was diagnostic. Six (55%) patients displayed poor initial allograft
      function and were classified as early presenters of RACS. Allograft function
      improved dramatically upon decompression. CONCLUSIONS: Clinicians must remain
      aware of RACS as a potential diagnosis when patients display rapid deterioration
      in kidney performance after good initial allograft function. Doppler ultrasound
      is useful in diagnosing late presenters.

PMID- 16647349
TI  - Discordance between lactate and base deficit in the surgical intensive care unit:
      which one do you trust?
AB  - PURPOSE: Both lactate and base deficit (BD) are used as predictors of injury
      severity and mortality. We examined the significance of these measures when used
      in combination, and particularly when they provide conflicting data. METHODS: We
      reviewed all intensive care unit patients with simultaneously obtained lactate
      and BD measurements. The ability to predict mortality and hospital stay was
      compared alone, in combination, and when there was disagreement between the
      measures. Receiver operating characteristic curves were generated to compare
      predictive abilities. RESULTS: There were 1,298 patients with 12,197 sets of
      paired laboratory data; 1,026 trauma patients and 272 surgical patients. Lactic
      acidosis was present in 41% and a significant BD level (> 2) was found in 52%.
      Nonsurvivors had higher admission lactate (6.2 vs. 3.3) and base deficit (6.1 vs.
      3.2) levels than survivors (both P < .01), with a modest correlation (r = .52)
      between the measures. The admission lactate and BD levels had similar predictive
      ability for mortality, with areas under the receiver operating characteristic
      curve of .7 and .66, respectively (both P < .01). However, the predictive ability
      of the BD level decreased significantly during the intensive care unit stay
      (area, .5) compared with lactate level (area, .68). Lactate and BD levels
      disagreed in 44% of all laboratory sets. In patients with a normal lactate level
      (< 2.2), the BD level had no predictive ability for mortality (area, .48; P =
      .26). However, in patients with a normal BD level (< 2.0), the lactate level
      retained its predictive ability for mortality (area, .67; P < .01). Lengths of
      stay were longer among patients with an increased lactate level, even when the BD
      level was normal. There was no improvement in predictive ability using a
      combination of the 2 measures. CONCLUSIONS: Both lactate and BD levels may be
      used to identify lactic acidosis and predict mortality at admission. Increased
      lactate levels predict mortality and a prolonged course regardless of the
      associated BD level, whereas an increased BD level has no predictive value if the
      lactate level is normal.

PMID- 16647350
TI  - Management of splenic pseudocysts following trauma: a retrospective case series.
AB  - BACKGROUND: Post-traumatic splenic pseudocysts are uncommon. The optimal
      treatment is not well defined. METHODS: A retrospective chart review was
      conducted at the three adult hospitals in the Calgary Health Region. RESULTS: Six
      cases of splenic pseudocysts were found over a 6-year period. One splenic
      pseudocyst spontaneously resolved. A second splenic cyst was removed by open
      splenectomy. The remaining 4 patients were all first treated with percutaneous
      drainage. However, 3 of the 4 cysts recurred. Two of these 3 recurrent cysts were
      treated with laparoscopic fenestration, and all subsequently recurred; 1 of these
      patients later developed a splenic abscess. The third patient had a repeat
      percutaneous drain with subsequent recurrence. The last patient died of sepsis
      secondary to an iatrogenic punctured colon. CONCLUSIONS: Percutaneous drainage
      and laparoscopic fenestration have an unacceptably high rate of failure. Partial
      or complete splenectomy should be considered for young and otherwise healthy
      patients who have large symptomatic splenic pseudocysts.

PMID- 16647351
TI  - Outcomes among women younger than age 40 in a state breast cancer screening
      program.
AB  - BACKGROUND: The value of entering women younger than age 40 in breast cancer
      screening programs (SPs) remains unclear. METHODS: Data from the Oregon Breast
      and Cervical Cancer Program (BCCP) for the period December 31, 2000 through July
      1, 2003 were reviewed with a focus on women 39 years of age or younger.
      Information on cancers detected in this group was extracted from The Oregon State
      Cancer Registry. RESULTS: Of the 13,636 women screened, 797 (5.8%) were younger
      than 40 (mean age 31.9 years). A total of 20.6% of the women were asymptomatic
      and therefore represented true incidence screening, while 79.4% were referred to
      the program for symptoms (prevalence screen). A total of 125 biopsies were done
      out of 797 women, which yielded 5 cancers. All 5 of these patients were
      symptomatic at presentation and had a negative family history. CONCLUSIONS: There
      are as yet no data in our state breast cancer SP to support screening of
      asymptomatic women younger than 40.

PMID- 16647352
TI  - The evaluation and treatment implications of isolated pulmonary nodules in
      patients with a recent history of breast cancer.
AB  - BACKGROUND: Breast cancer patients with pulmonary lesions are often assumed to
      have metastatic disease and treated palliatively. We evaluated the proportion of
      these patients who actually have primary lung tumor (PLT) and assessed their
      outcome. METHODS: We performed a 10-year retrospective review of the cancer
      registry in a community hospital system. RESULTS: Among 54 breast cancer patients
      with pulmonary nodules, biopsy was pursued in 30. Although metastatic breast
      cancer (MBC) was presumed in 24, biopsy showed MBC in 9 patients and PLT in 21.
      The two groups differed in age, stage, breast tumor size, nodal involvement, and
      estrogen receptor (ER) positivity. However, no variable excluded the possibility
      of PLT. Of those with PLT, 11 had early-stage lung disease; 9 underwent curative
      resection. CONCLUSIONS: Women with breast cancer and 1 or more pulmonary lesions
      without evidence of other metastatic disease require work-up of pulmonary
      lesions. Aggressive evaluation can afford treatment of lung cancer and impact
      survival.

PMID- 16647353
TI  - A prospective analysis of microsatellite instability as a molecular marker in
      colorectal cancer.
AB  - BACKGROUND: Microsatellite instability (MSI) may be a molecular marker of
      colorectal tumor biology. We sought to evaluate the incidence and significance of
      MSI in an unselected colorectal cancer population. METHODS: Colorectal cancer
      cases from a community health system were prospectively evaluated for MSI and
      patient outcomes monitored. RESULTS: Of 240 eligible, 140 underwent testing; 43
      (31%) had high-frequency MSI (MSI-H). Those with MSI-H tumors presented with
      earlier disease stage (P = .014) and lymphocytic infiltration (P < .001). Stage
      III MSI-H patients trended toward improved disease-free survival (P = .065). MSI
      H patients were more likely to have other primary malignancies. CONCLUSIONS:
      Prevalence of MSI-H in the general colorectal cancer population is higher than
      previously reported. MSI testing of colorectal cancers is useful as part of a
      molecular profile to stratify patients for prognosis, treatment, and further
      study. Patients with MSI-H tumors are more likely to have other primary
      malignancies, suggesting a role for heightened screening.

PMID- 16647354
TI  - Early removal of postmastectomy drains is not beneficial: results from a halted
      randomized controlled trial.
AB  - BACKGROUND: Closed-suction drainage to reduce seromas is standard after
      mastectomy. This study evaluates the safety of early drain removal. METHODS:
      Women undergoing mastectomy were randomized to early removal on postoperative day
      2 or standard removal (< 30 mL drainage in 24 hours or postoperative day 14).
      Primary endpoints were time to drain removal and physician visits. Secondary
      endpoints were number of seroma aspirations, drain reinsertions, and infections.
      RESULTS: Twenty-seven patients were recruited before an interim analysis was
      performed to address safety concerns. Three patients withdrew before trial
      completion, leaving 14 patients in the standard group and 10 in the early group.
      Patients in the standard group had significantly fewer seroma aspirations, fewer
      drain reinsertions, and fewer physician visits. The trial was halted because of
      the higher rate of events in the early group. CONCLUSION: Surgical drains cannot
      be safely removed on postoperative day 2 after mastectomy. Early removal
      significantly increases the occurrence of seromas requiring treatment.

PMID- 16647355
TI  - Metaplastic breast cancer: clinical significance.
AB  - BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare poorly differentiated
      breast cancer characterized by coexistence of ductal carcinoma with areas of
      matrix producing, spindle-cell, sarcomatous, or squamous differentiation;
      ER/PR/HER2 negativity; and a reputation for poor outcome. METHODS: The Swedish
      Cancer Institute prospective breast cancer database (> 6500 patients; 1990-2005)
      has 24 MBC cases that were compared with typical breast cancer cases matched for
      age, date of diagnosis, stage, and ER/PR/HER2 status. RESULTS: The mean
      metaplastic primary tumor diameter was 2.5 cm. The histological/nuclear grade was
      high in 21 of 24 cases. No patient had distant metastasis. ER and/or PR receptor
      status was negative in all cases. HER2 was negative in 10 of 11 cases tested.
      EGFR (HER1) was positive in 7 of 7 cases tested. All patients had sentinel and/or
      axillary lymph node dissection and surgical resection; 18 received chemotherapy
      and 22 had radiation therapy. Four patients had distant recurrences 5 to 88
      months from diagnosis. Five-year survival was 83% (95% confidence interval, 66
      100%). Comparison with matched typical breast cancer cases revealed no major
      significant difference in multidisciplinary treatment patterns, recurrence, or
      survival. CONCLUSION: MBC is associated with poor prognostic indicators, but
      outcomes comparable with matched typical breast cancer cases can be achieved with
      routine aggressive multidisciplinary care. Increased, expression of EGFR (HER1)
      provides an opportunity for targeted tumor therapy.

PMID- 16647356
TI  - Ex vivo sentinel lymph node mapping in colon cancer: improving the accuracy of
      pathologic staging?
AB  - BACKGROUND: A subset of patients with colon cancer staged by conventional methods
      have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel
      lymph node (SLN) mapping and staining by immunohistochemistry is a technique that
      may identify such occult micrometastases, thereby upstaging patients with
      positive findings. The purpose of this study was to determine whether ex vivo SLN
      mapping in colon cancer could be applied successfully to patients at our
      institution. METHODS: Seventeen patients with intraperitoneal colon tumors
      undergoing resection were studied prospectively. SLNs were identified as the
      first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue
      dye. Additional lymph nodes were harvested and processed in accordance with
      standard pathologic evaluation for colon cancer. All nodes were examined after
      routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were
      analyzed further by multilevel sectioning and immunohistochemistry staining using
      anticytokeratin monoclonal antibody. RESULTS: Of the 17 study patients, SLNs were
      identified in 16 (94%) cases. The SLN was the only positive node in 3 patients.
      An identified SLN was positive (by H&E) in all patients with associated positive
      non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4
      54). Overall, SLNs accurately reflected the status of the entire lymph node basin
      in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially
      were upstaged after further SLN analysis. The negative predictive value for SLN
      mapping was 89%. CONCLUSIONS: The ex vivo technique of SLN mapping for colon
      cancer is feasible. In the current study, SLN results were concordant with non
      SLNs in the majority of patients. Furthermore, this technique may have upstaged 2
      (12%) patients. Whether this ultimately will affect overall survival has yet to
      be determined.

PMID- 16647357
TI  - Initial experience with a general population colorectal cancer screening clinic.
AB  - BACKGROUND: Recognition of adenoma to carcinoma progression has established
      colorectal cancer as a preventable malignancy. Colorectal cancer is, therefore,
      an ideal malignancy for preventative screening given the presence of a benign
      precursor. We set out to establish a pilot low-risk endoscopic screening clinic
      and we discuss our initial results. METHODS: A retrospective chart review of all
      patients referred to a new low-risk colorectal cancer endoscopic screening clinic
      from October 1, 2004 to September 30, 2005 was performed. Those patients found to
      have adenomas or carcinomas were analyzed further regarding location of neoplasm
      and pathologic findings. RESULTS: A total of 379 low-risk patients attended the
      colorectal cancer screening clinics. The age range of the patients was 50 to 86
      years. The male to female ratio was 254 to 128. A total of 257 patients had
      flexible sigmoidoscopy as the initial screen, 24 patients had partial
      colonoscopy, and 98 patients had complete initial colonoscopy. A total of 152
      patients had polyps removed, of which 63 patients had adenomas, 3 had
      adenocarcinomas, 1 had a carcinoid, and the remaining had an assortment of
      nonneoplastic polyps. Of the 67 patients with neoplasms, 50 were left of the
      splenic flexure, 11 were right of the splenic flexure, and 5 patients had lesions
      both proximal and distal to the flexure. Thirty-two of the 67 patients had
      complete colonoscopy at the initial procedure and, thus far, 21 patients have had
      completion colonoscopies, of which 9 patients had further neoplasms identified
      beyond the splenic flexure. All 3 patients with carcinoma had early tumors
      resected with curative intent, with negative margins and negative nodes.
      CONCLUSIONS: Our initial experience with a low-risk general population colorectal
      cancer endoscopic screening clinic yielded 18% of patients with neoplasms, and 1%
      had curable cancers resected.

PMID- 16647358
TI  - Outcomes of a laparoscopic approach for total abdominal colectomy and
      proctocolectomy.
AB  - BACKGROUND: The role of laparoscopy for total abdominal colectomy (TAC) and total
      proctocolectomy (TPC) has been controversial given its technical difficulty, high
      conversion rate, and complication rate. Recent studies have documented its
      efficacy for experienced laparoscopic surgeons. The outcomes of a prospective
      series of patients undergoing TAC and TPC are presented. METHODS: A consecutive
      series of patients undergoing TAC or TPC were identified from prospectively
      collected data during 2002 to 2005. The database reflects a single colon and
      rectal surgical specialty practice. Patient characteristics, surgical parameters,
      and patient outcomes were documented. RESULTS: From a total of 51 patients, 19
      underwent TAC and 32 underwent TPC. There were 26 women and 35 men. The mean
      patient age was 40 years (range, 17-74 y). The mean body mass index was 25
      (range, 19-38). Twelve patients underwent surgery for colonic inertia, 2 for
      familial adenomatous polyposis, and 37 for chronic ulcerative colitis. Of the
      ulcerative colitis patients, 8 patients had toxic colitis, 4 had dysplasia, and
      25 had medically refractory disease. The overall mean surgical time was 163
      minutes (range, 85-227 min): the mean surgical time for TAC was 131 minutes
      (range, 85-189 min) and for TPC was 197 minutes (range, 131-227 min). The overall
      mean blood loss was 200 mL (range, 75-500 mL). The mean length of stay was 4.8
      days (range, 2-16 d). Open conversion was required in 5 patients: 3 with toxic
      colitis (38%), and 2 during elective colectomy (4.8%). Ten complications occurred
      (19.7%) with no mortality. CONCLUSIONS: A laparoscopic approach to TAC and TPC is
      efficacious and safe. It is a viable alternative to open surgery for surgeons
      experienced with the laparoscopic approach to colectomy. Patients with toxic
      colitis may undergo a laparoscopic approach but will have a higher open
      conversion rate.

PMID- 16647359
TI  - Self-assessment during a 2-day laparoscopic colectomy course: can surgeons judge
      how well they are learning new skills?
AB  - BACKGROUND: The objectives of this study were to (1) establish the utility of an
      assessment tool for participants in a laparoscopic colectomy course and (2) to
      determine the accuracy of technical skill self-assessment in this group. METHODS:
      Twenty-two surgeons enrolled in a 2-day course participated. During the animal
      laboratory, each participant's operative performance was videotaped. Participants
      completed a global rating scale (GRS) instrument to self-assess their
      performances. By using the same GRS, 2 trained raters independently assessed each
      performance by videotape review. RESULTS: For the trained raters, the GRS showed
      excellent interrater reliability (r = .76, P < .001). There was no correlation
      between trained rater scores and self-assessment scores. Furthermore, the trained
      rater scores (mean, 2.62 and 2.99) were significantly lower than the self
      assessment scores (4.05, P < .001). CONCLUSIONS: Surgeons consistently
      overestimated their performance during a laparoscopic colectomy course as
      measured by reliable GRS. This finding highlights the issue of credentialing and
      the importance of preceptorship for surgeons completing such courses.

PMID- 16647360
TI  - Prospective comparison of early and late experience with laparoscopic
      adrenalectomy.
AB  - BACKGROUND: Laparoscopic adrenalectomy has gained acceptance in the treatment of
      adrenal tumors. We examine our initial 73 patients and highlight the change in
      patient selection and outcome that experience brings. METHODS: A prospective
      study from 2000 to 2005 enrolled 73 consecutive laparoscopic adrenalectomy
      patients at the University of British Columbia and Vancouver General Hospitals.
      RESULTS: Forty patients in an initial cohort and 33 in the follow-up group
      underwent adrenalectomy. The follow-up group had a greater proportion of
      pheochromocytomas (33.3% versus 7.5%), larger tumors (4.25 versus 1.97 cm), and
      higher American Society of Anesthesiologist (ASA) scores (2.82 versus 2.38) and
      lengths of stay (2.35 versus 1.55 days). Minor complication rates (12% versus 5%)
      were also higher. Operative times and blood loss were similar. Pheochromocytoma
      was associated with higher ASA scores and longer lengths of stay. Operative times
      and blood loss were not affected by diagnosis. CONCLUSIONS: Increasing experience
      in laparoscopic adrenalectomy allows broadening of indications to include a
      sicker patient population.

PMID- 16647361
TI  - Evaluating learning and knowledge retention after a continuing medical education
      course on total mesorectal excision for surgeons.
AB  - The purpose of this study was to determine whether knowledge gained (as
      determined by a formal course test) by surgeons in a continuing education course
      on total mesorectal excision and rectal cancer management is retained 1 year
      later. A formal course test had been previously developed and validated. The test
      evaluated course content including pelvic anatomy, surgical techniques, imaging,
      pathology, adjuvant therapies, and cancer and functional outcomes. Validation was
      determined by the absence of change in pre- and posttest scores of the "expert"
      course instructors (n = 8, P = .6) and by a linear correlation in test scores
      with increasing level of general-surgery resident training (n = 16, P = .001).
      Significant learning by the 58 surgeons taking the course had been shown by
      improvement in test scores from before the course (mean score 19) to after the
      course (mean score 25.3, P = .001, out of a possible 33 total mark). At 1 year
      after the course, those course participants (n = 44, 76%) who had provided
      postcourse contact information were asked to complete the course test again.
      Responses were received from 18 surgeons (41% of those surveyed, 31% of the
      original course participants). The mean score on the test after 1 year was 23.8.
      Compared with the immediate posttest scores, there was no significant knowledge
      loss over the year (P = .09). We conclude that knowledge acquired during a
      continuing education course for surgeons on total mesorectal excision and rectal
      cancer management is retained 1 year later.

PMID- 16647362
TI  - Laparoscopic aortic reconstruction: early experience.
AB  - BACKGROUND: Laparoscopic reconstruction of the abdominal aorta has been described
      as early as 1993. The techniques used have varied but all have been labor
      intensive. With advances in laparoscopic technique and the available tools, the
      role in aortic reconstruction is expanding. The high cost of endovascular
      techniques as well as the morbidity of traditional open surgery has resulted in
      an increased focus on the laparoscopic approach. Our goal was to determine the
      feasibility of this technique. METHODS: Retrospective review of the charts of
      patients undergoing laparoscopic aortobifemoral bypass grafting for chronic lower
      limb occlusive disease. RESULTS: Thirteen patients were selected for the
      procedure. Ten were completed successfully and form the basis of the report. The
      average length of stay was 6.7 days compared with a historic cohort of 12 days.
      The average operative time was 6.5 hours, more than twice as long as the open
      technique. There was a tendency to lower blood replacement and less abdominal
      pain. One patient suffered a stroke postoperatively; no deaths occurred.
      CONCLUSION: This procedure is technically challenging but can be performed safely
      and successfully with adherence to several key anatomic principles. More
      widespread adoption of this technique may lead to improvements in the instruments
      and other technologies. Our very early experience is encouraging. There appear to
      be benefits of reduced length of stay, but improved operative times will be
      required to make this technique truly valuable.

PMID- 16647363
TI  - Marriage of professional and technical tasks: a strategy to improve obtaining
      informed consent.
AB  - BACKGROUND: Education in obtaining informed consent, combined with technical
      training using a stepwise approach, may improve resident knowledge of, confidence
      in, and frequency of obtaining consent for bedside procedures. METHODS: Surgical
      trainees were randomized to receive a lecture on obtaining informed consent.
      Knowledge of, confidence in, and frequency of obtaining consent were assessed.
      Subsequent first-year residents received combined technical and consent training
      using a stepwise approach. Residents listed key steps for procedures before and
      after training, were observed for consent and technical competency on patients,
      and were assessed on frequency of obtaining consent by follow-up chart review.
      RESULTS: Knowledge and confidence improved after lecture instruction, but consent
      rate (21%) did not. Stepwise training increased resident awareness of obtaining
      informed consent as a key step (19% to 77%) and increased frequency of obtaining
      consent (89% for proctored procedures and 79% in follow-up). CONCLUSIONS:
      Education alone improves knowledge but not practice of obtaining consent.
      Teaching the consent process concomitantly with technical training may increase
      awareness and performance of obtaining informed consent for bedside procedures.

PMID- 16647364
TI  - The resident view of professionalism behavior frequency in outstanding and "not
      outstanding" faculty.
AB  - BACKGROUND: Professionalism assessment has become necessary for all postgraduate
      training programs because it is now required for accreditation. To validate the
      novel items we generated to assess professionalism, we tested whether residents'
      ratings of faculty they judged as outstanding in professionalism would be
      distinguishable from those they judged as not outstanding. METHODS: Educators
      from core clinical disciplines generated 20 items assessing professionalism
      behaviors on a 7-point frequency scale anchored by "always" and "never." Thirty
      five surgical and pediatric residents completed the form twice, anonymously
      rating 1 faculty member they judged as outstanding and another they judged as not
      outstanding. RESULTS: The residents produced 69 faculty ratings with means that
      differed significantly on all items between the outstanding and not-outstanding
      faculty. The form was highly unidimensional, with the primary factor's eigenvalue
      being 11.5 and Cronbach's alpha being 0.97. Groups differed most on items, ie,
      "listens well," "inspires trust," "answers questions directly," and "demonstrates
      respect for all." CONCLUSION: The behaviors that best distinguished clinical
      faculty judged by residents as outstanding professionals were listening,
      trustworthiness, answering directly, and respect.

PMID- 16647365
TI  - Intra-abdominal cystic lymphangioma.
AB  - Cystic lymphangioma is an uncommon intra-abdominal lesion that is an occasional
      incidental finding. We report herein the case of a 27-year-old woman with a 3
      year history of abdominal pain due to a large intra-abdominal cystic
      lymphangioma. The lesion was removed surgically with a complete resection that is
      the optimal treatment with excellent prognosis.

PMID- 16647366
TI  - National survey of surgical morbidity and mortality conferences.
AB  - BACKGROUND: Morbidity and mortality conferences historically have been a
      paramount meeting for education and quality assurance within surgical departments
      of teaching institutions. The purpose of this survey was to assess the present
      educational value and the quality assurance aspect of surgical mortality
      conferences. METHODS: Surveys were sent to every academic surgical training
      program director within the United States and Canada (n = 127) and queried the
      general format and an individual's experience and attitude toward their
      institutions conference. RESULTS: A total of 546 individuals from 34 institutions
      returned completed surveys. The survey findings showed that 74% of these surgical
      departments discussed all deaths and 50% discussed all complications. There was
      general agreement that surgical morbidity and mortality conferences are of good
      educational value and effective in reducing future error. The majority of
      respondents expressed that evidence-based literature should be the primary basis
      of discussion, with comprehensive presentations that focus on analysis of error.
      CONCLUSIONS: This survey showed that morbidity and mortality conferences are both
      educational and perceived by the respondents as effective in reducing future
      error.

PMID- 16647367
TI  - Lengthening of small bowel mesentery: stepladder incision technique.
AB  - The surgical option of choice in most patients with mucosal ulcerative colitis or
      familial adenomatous polyposis is restorative proctocolectomy with ileal pouch
      anal anastomosis. The tension-free anastomosis is one of the most critical steps
      but may be technically difficult or impossible in some patients because of
      shortened small bowel mesentery. Various techniques have been described to
      increase the length of small bowel mesentery. These techniques usually involve
      selective division of mesenteric blood vessels and meticulous dissection. We
      describe a new technique of stepladder transverse, transmesenteric incisions in
      the avascular windows of small bowel mesentery. This provides additional small
      bowel length without compromising blood supply to the pouch and a simple and safe
      method of increasing the length of small bowel mesentery. To date, no
      complications have been reported using this technique.

PMID- 16647368
TI  - Three-port laparoscopic cholecystectomy by harmonic dissection without cystic
      duct and artery clipping.
AB  - BACKGROUND: The technique of laparoscopic cholecystectomy (LC) still has areas of
      refinements. To decrease the number of ports, a cannula may be replaced by a
      percutaneous suture suspension of the gallbladder. The risk of tissue injury
      caused by repeat blind extraction and insertion of various instruments in and out
      of the abdomen may be decreased by the use of the multipurpose harmonic
      dissector. METHODS: One hundred consecutive patients with symptomatic
      cholelithiasis underwent 3-port LC entirely performed by harmonic dissector
      without cystic duct and artery clipping. RESULTS: In 8 cases, a fourth trocar was
      necessary. In 2 cases, the cystic duct was clipped after an unsafe ultrasound
      sealing. In 1 case, continuous bleeding from the liver required the use of
      diathermy. No common bile duct injury was registered. CONCLUSIONS: The 3-port
      harmonic LC is a feasible, effective, and safe technique.

PMID- 16647370
TI  - Solutions to the problem of multiple pregnancy with IVF.

PMID- 16647372
TI  - Dissecting and temporarily resuspending the adherent ovary.

PMID- 16647373
TI  - Aromatase inhibitors: the next generation of therapeutics for endometriosis?
AB  - OBJECTIVE AND DESIGN: To review the role of aromatase inhibitors (AIs) in the
      treatment of endometriosis. CONCLUSION(S): Endometriosis is a common estrogen
      dependent disorder that can result in substantial morbidity, including pelvic
      pain, multiple operations, and infertility. Approximately only half of women with
      endometriosis get pain relief from existing medical or surgical treatments.
      Medical treatments usually are directed at inhibiting estrogen action or its
      production from the ovaries and do not address local estrogen biosynthesis by the
      aromatase enzyme in endometriotic lesions. A single gene encodes aromatase, which
      is the final enzyme in the estrogen biosynthesis pathway, and its inhibition
      effectively eliminates estrogen production. The recently introduced highly
      specific AIs have successfully treated pelvic pain and significantly reduced the
      lesion size. In premenopausal women, an AI alone may induce ovarian
      folliculogenesis, and thus AIs are combined with a progestin, a combination oral
      contraceptive, or a GnRH analogue. The side-effect profile of AIs administered in
      combination with an oral contraceptive or a progestin is remarkably benign. We
      review herein the published clinical evidence for the use of AIs in the treatment
      of endometriosis.

PMID- 16647374
TI  - Obesity and androgens: facts and perspectives.
AB  - OBJECTIVE: This review discusses androgen status in male and female obesity,
      according to their specific phenotype, and the main mechanisms responsible.
      DESIGN: Published data in the literature of the last 20 years represented the
      basis of most of the data and concepts incorporated in the review. RESULT(S):
      Obesity is associated with profound alterations in androgen secretion, transport,
      metabolism, and action, according to a dichotomous behavior depending on sex.
      Obese men are characterized by a progressive decrease of testosterone levels with
      increasing body weight, whereas obese women, particularly those with the
      abdominal phenotype, tend to develop a condition of functional hyperandrogenism.
      Reduced sex hormone-binding globulin synthesis and circulating blood levels
      represent the sole common mechanism which is responsible in both sexes. Among
      other still partially undefined factors, mechanisms potentially responsible for
      the sex dichotomy in androgen levels involve specific alterations of gonadotropin
      secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen
      receptors, specific steroidogenic enzymes in the peripheral tissues, and,
      possibly, ghrelin. In both sexes, androgens play an important role in determining
      the sex-dependent pattern of body fat distribution. Moreover there are
      theoretical possibilities that low testosterone in men and high free testosterone
      fraction in women may play a role in the development of the metabolic syndrome.
      This is exemplified by the well defined association between obesity and other
      features of the metabolic syndrome in women with polycystic ovary syndrome and in
      hypogonadal men. The effects of androgen and antiandrogens in obese men and women
      also represent arguments in favor of this association. CONCLUSION(S): Given the
      fundamental role of sex hormones in the regulation of body composition, fuel
      homeostasis, and reproduction in humans, more emphasis should be placed on the
      potential role of androgen dysregulation in the pathophysiology of different
      obesity phenotypes and the metabolic syndrome.

PMID- 16647375
TI  - HOXA10 expression in ectopic endometrial tissue.
AB  - OBJECTIVE: To evaluate HOXA10 expression in endometriosis. DESIGN: Laboratory
      study using human tissue. SETTING: Academic research center. PATIENT(S): Eutopic
      endometrial tissue was collected from 20 fertile women without endometriosis.
      Ectopic endometrial tissues from pelvic peritoneum, ovary, and lung parenchyma
      were collected from 20 women undergoing surgery for endometriosis.
      INTERVENTION(S): HOXA10 protein expression and localization with
      immunohistochemistry. MAIN OUTCOME MEASURE(S): Quantitative analysis of HOXA10
      expression, according to H score. RESULT(S): Both eutopic and ectopic endometrial
      tissue expressed HOXA10. Ectopic endometrial tissue had lower stromal HOXA10
      expression compared with eutopic endometrium. The mean H score for stromal
      expression of HOXA10 was 7.6 in eutopic endometrium and 1.3 in ectopic
      endometrial tissue. Glandular epithelium from both eutopic and ectopic
      endometrium had similarly low HOXA10 expression. HOXA10 was also expressed at low
      levels in lung parenchyma containing endometriosis and in ovarian endometriomas.
      CONCLUSION(S): HOXA10 is expressed in endometriosis at locations outside of the
      normal HOXA10 expression domain, where it is likely necessary to impart
      endometrial developmental identity on endometriosis. HOXA10 might be necessary
      for "de novo" endometrial development. However, the diminished expression of
      HOXA10 in ectopic endometrium might not allow for normal endometrial development
      and might contribute to the pathogenesis of endometriosis by creating P
      resistance.

PMID- 16647376
TI  - Alteration of TH1 and TH2 cells by intracellular cytokine detection in patients
      with unexplained recurrent abortion before and after immunotherapy with the
      husband's mononuclear cells.
AB  - OBJECTIVE: To elucidate the possible mechanisms of immunotherapy for unexplained
      recurrent aborters using their husband's mononuclear cells. DESIGN: Prospective
      clinical study. SETTING: Institutional practice at the Outpatient Clinic for
      Infertility, Niigata University Medical Hospital. PATIENT(S): Fifty-two
      unexplained recurrent aborters were chosen as an experimental group.
      INTERVENTION(S): Each patient was injected with her husband's mononuclear cells
      as immunotherapy. Peripheral blood was obtained from the patients. MAIN OUTCOME
      MEASURE(S): The percentage of CD4-positive cells, TH1 cells, TH2 cells, and the
      TH1/TH2 ratio were analyzed in the patients before and after immunotherapy. The
      same analyses were performed in the successful and the unsuccessful group.
      RESULT(S): To date, 42 of the 52 patients have become newly pregnant. Of the 42,
      34 patients have already delivered (successful group) and 3 are now pregnant,
      while the remaining 8 cases experienced repeated abortion (unsuccessful group).
      The percentage of TH2 cells significantly increased in the total patient
      population, while the TH1/TH2 ratio significantly decreased in the total patient
      population and in the successful group. CONCLUSION(S): These findings suggest
      that immunotherapy with the husband's mononuclear cells for unexplained recurrent
      abortion induces a dominant state of TH2 cells in the patients.

PMID- 16647377
TI  - Intraoperative and postoperative lower genital tract changes after global
      endometrial ablation using the Hydro ThermAblator device.
AB  - OBJECTIVE: To identify any heat transfer areas in the lower genital tract during
      a Hydro ThermAblator (HTA) (BEI Medical Systems) procedure and to characterize
      the changes in the cervix that occur in the immediate weeks after an HTA
      treatment. DESIGN: A prospective cohort study (Canadian Task Force classification
      II-3). SETTING: A university hospital in the United Kingdom. PATIENT(S): Twenty
      five patients with menorrhagia. INTERVENTION(S): All patients underwent global
      endometrial ablation using the HTA device. Infrared thermal camera imaging of the
      lower genital tract was performed per-operatively, and colposcopic examinations
      of the cervix were performed at 2 and 4 weeks after the operation. MAIN OUTCOME
      MEASURE(S): The surface temperature rise of the cervix and vagina during a
      procedure. RESULT(S): Thermal temperature measurements of the lower genital tract
      in five patients and colposcopic examination at 2 and 4 weeks after the
      procedure. The maximum temperatures recorded during a procedure were those of the
      cervix, reaching 36.5 degrees C. Colposcopic images at 2 weeks showed that 15% of
      patients had a whitish discoloration of the cervix. At 4 weeks, the appearance of
      the cervix was normal. CONCLUSION(S): This study shows that during an HTA
      treatment cycle using a bivalve speculum to visualize the cervix, no area of the
      lower genital tract reaches a temperature at which thermal damage may occur. A
      whitish change in the cervix at 2 weeks is normal, and the lower genital tract
      should appear normal 4 weeks after the procedure.

PMID- 16647378
TI  - X-chromosome inactivation and ovarian age during the reproductive years.
AB  - OBJECTIVE: To explore whether skewed X-chromosome inactivation (XCI) is related
      to indicators of ovarian age. DESIGN: The XCI skewing percent and indicators of
      ovarian age were measured in women with recent pregnancy losses and women with
      recent livebirths. All analyses adjust for chronologic age and pregnancy outcome.
      SETTING: Hospital in eastern central New York. PATIENT(S): One hundred thirty-six
      women with informative XCI assays: 83 with index pregnancy losses and 53 with
      livebirths. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary
      indicators of ovarian age were antral follicle count, levels of FSH and inhibin
      B. A secondary indicator was level of estradiol (E2). RESULT(S): The XCI skewing
      percent, defined either continuously or categorically (> or =90%), was unrelated
      to the indicators of ovarian age. The sample was large enough to rule out as
      unlikely a modest decline in antral follicle count or a modest increase in FSH in
      relation to skewed XCI. CONCLUSION(S): X-chromosome anomalies are associated with
      skewed XCI and with premature ovarian failure. Our data raise the possibility
      that X-chromosome anomalies may not be an important influence on ovarian aging in
      menstruating women.

PMID- 16647379
TI  - Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with
      46,XX spontaneous premature ovarian failure.
AB  - OBJECTIVE: To investigate mutations in the human KIT ligand gene (KITLG) gene as
      a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand
      gene, known also as human stem cell factor, is the ligand of the c-kit
      transmembrane tyrosine kinase receptor (KIT). This ligand-receptor interaction is
      known to play important roles in mouse germ cell migration and proliferation.
      DESIGN: Cross-sectional study. SETTING: Clinical research center. PATIENT(S):
      Forty women with 46,XX spontaneous premature ovarian failure. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Single-stranded conformational polymorphism
      analysis and DNA sequencing. RESULT(S): We found one nucleotide change of the
      KITLG coding region (811G-->T) that led to an alteration of the amino acid
      composition of the KITLG protein in one Caucasian patient (Asp210Tyr). However,
      we found the same alteration in two normal control Caucasian samples. Three
      nucleotide substitutions were found in the noncoding exon of KITLG (exon 10). We
      also identified two intronic polymorphisms. Thus, we did not identify a single
      significant mutation in the coding region of the KITLG gene in any of 40 patients
      (upper 95% confidence limit is 7.2%). CONCLUSION(S): Mutations in the coding
      regions of the KITLG gene appear not to be a common cause of 46,XX spontaneous
      premature ovarian failure in North American women.

PMID- 16647380
TI  - Safety of simple cystectomy in patients with unilateral mucinous borderline
      tumors.
AB  - OBJECTIVE: To report on ovarian carcinoma development after cystectomy for a
      borderline mucinous ovarian tumor. DESIGN: Case report. SETTING: A French
      comprehensive cancer center. PATIENT(S): One patient who developed recurrence in
      the form of an invasive ovarian carcinoma after simple cystectomy for a
      borderline mucinous ovarian tumor. INTERVENTION(S): Simple cystectomy. MAIN
      OUTCOME MEASURE(S): Clinical outcome. RESULT(S): A 22-year-old nulliparous
      patient underwent laparoscopic cystectomy. Histological examination revealed a
      borderline mucinous ovarian tumor. No additional treatment was prescribed. Two
      years later, the patient relapsed with a malignant mucinous ovarian carcinoma.
      She underwent surgical resection and staging, including hysterectomy, bilateral
      adnexectomy, omentectomy, and pelvic and para-aortic lymphadenectomy, and
      platinum-based chemotherapy. CONCLUSION(S): Recurrence in the form of invasive
      ovarian carcinoma may occur in the same ovary after cystectomy in cases of
      borderline mucinous ovarian tumor. An approach combining systematic unilateral
      salpingo-oophorectomy and strict monitoring is preferable to simple cystectomy.
      Such treatment enables preservation of reproductive potential and reduces the
      risk of developing invasive carcinoma.

PMID- 16647381
TI  - Inguinal ovaries associated with Mullerian agenesis: case report and review.
AB  - OBJECTIVE: To report on a patient with Mullerian agenesis (MA) and inguinal
      ovaries and to review the pertinent literature. DESIGN: Case report and
      literature review. SETTING: Clinical. PATIENT(S): A 12-year-old girl.
      INTERVENTION(S): Magnetic resonance imaging, review of prior ovarian biopsies,
      karyotyping. MAIN OUTCOME MEASURE(S): Accuracy of diagnosis and preservation of
      ovarian function. RESULT(S): A 12-year-old girl with MA and bilateral inguinal
      ovaries is reported. An exhaustive review of the English literature on this rare
      association revealed only seven other well-documented such cases. Management of
      this condition involves reduction of the ovaries into the pelvis. CONCLUSION(S):
      The association of MA and bilateral inguinal ovaries is rare and possibly
      underreported. Ideal management consists of surgical reduction of the gonads into
      the pelvic cavity as soon as they are discovered, to decrease the risk of ovarian
      torsion and loss of ovarian function.

PMID- 16647382
TI  - Metformin hydrochloride and recurrent miscarriage in a woman with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To report the effect of metformin treatment on a patient with
      recurrent miscarriage (RM) and polycystic ovary syndrome (PCOS). DESIGN: Case
      report. SETTING: University department of obstetrics and gynecology, Italy.
      PATIENT(S): A woman complaining of RM who had PCOS and insulin resistance.
      INTERVENTION(S): Clinical, biochemical, and instrumental assessments. MAIN
      OUTCOME MEASURE(S): Administration of metformin hydrochloride before and
      throughout pregnancy. RESULT(S): After 3 months of treatment, the patient became
      pregnant. The pregnancy had a physiologic development, and at 39 weeks of
      gestation, the patient spontaneously delivered a healthy infant. CONCLUSION(S):
      Metformin has shown to be effective in an insulin-resistant PCOS woman with RM.

PMID- 16647383
TI  - Comparison of bovine- and recombinant human-derived hyaluronidase with regard to
      fertilization rates and embryo morphology in a sibling oocyte model: a
      prospective, blinded, randomized study.
AB  - The objective of the present study was to compare a traditionally used bovine
      derived hyaluronidase (Hyase) with the newly developed recombinant human-derived
      enzyme product (Cumulase) in intracytoplasmic sperm injection (ICSI) procedures
      using a sibling oocyte model in a prospective randomized design. The results of
      the study demonstrate that Cumulase is safe and effective in an ICSI treatment
      program and can provide comparable if not improved parameters, including
      fertilization and embryo developmental rates.

PMID- 16647384
TI  - Effect of glycodelin on the production of vascular endothelial growth factor in
      cumulus cells.
AB  - Glycodelin modulates vascular endothelial growth factor (VEGF) production in
      cumulus cells in vitro. Patients with normal gonadotropin responses who were
      undergoing IVF demonstrated increased VEGF production to glycodelin, whereas poor
      responders had a decreased response to glycodelin.

PMID- 16647396
TI  - Is there life as an investigator after becoming a pediatric department chair?

PMID- 16647397
TI  - Understanding neurodevelopment in premature infants: applied chaos theory.

PMID- 16647398
TI  - Bone loss in children with Crohn disease: Evidence of "osteoimmune" alterations.

PMID- 16647399
TI  - Prognosis of biliary atresia: what can be further improved?

PMID- 16647400
TI  - Pediatric workforce: a look at pediatric hematology-oncology data from the
      American Board of Pediatrics.

PMID- 16647401
TI  - Early prediction of poor outcome in extremely low birth weight infants by
      classification tree analysis.
AB  - OBJECTIVE: To predict death or neurodevelopmental impairment (NDI) in extremely
      low birth weight infants by classification trees with recursive partitioning and
      automatic selection of optimal cut points of variables. STUDY DESIGN: Data from
      the Trial of Indomethacin Prophylaxis in Preterms were randomly divided into
      development (n=784) and validation sets (n=262). Three models were developed for
      the combined outcome of death (8 days to 18 months) or NDI (cerebral palsy,
      cognitive delay, deafness, or blindness at 18 months corrected age): antenatal:
      antenatal data; early neonatal: antenatal+first 3 days data; and first week:
      antenatal, first 3 days, and 4th to 8th days data. Decision trees were tested on
      the validation set. RESULTS: Variables associated with death/NDI in each model
      were: Antenatal: Gestation<or=25.5 weeks and antenatal steroids<7 days. Early
      neonatal: Birth weight<or=787 g and fluid intake>01 mL/kg/d. First week: Birth
      weight<or=787 g: transfusion>3 mL/kg/d. Birth weight>787 g: cranial echodense
      intraparenchymal lesion and transfusion>1 mL/kg/d. Correct classification rates
      were 61% to 62% for all models. CONCLUSIONS: The ability to predict long-term
      morbidity/death in extremely low birth weight infants does not improve
      significantly over the first week of life. Effects of different variables depend
      on age.

PMID- 16647402
TI  - Sex assignment for newborns with ambiguous genitalia and exposure to fetal
      testosterone: attitudes and practices of pediatric urologists.
AB  - OBJECTIVE: Sex assignment to newborns with ambiguous genitalia is controversial.
      Our objective was to determine the attitudes and practices of pediatric
      urologists on this subject. STUDY DESIGN: A survey of fellows in the Urology
      Section of the American Academy of Pediatrics was completed by 185/228 (81%). The
      survey referred to two cases, masculinized 46XX congenital adrenal hyperplasia
      (CAH) and 46XY cloacal exstrophy. Questions referred to sex assignment, timing of
      surgery, decision making process, and respondent demographics. RESULTS: For
      masculinized 46XX CAH, virtually all respondents favored female sex assignment.
      The most important factor was potential fertility. For 46XY cloacal exstrophy,
      two thirds favored the male sex. The most important factor was potential androgen
      brain imprinting, whereas in selecting female assignment, it was difficulty
      creating a functional phallus. Respondent characteristics associated with
      assigning female sex were longer duration in practice (>15 years) and affiliation
      with training programs. Most respondents advocated a team approach to decision
      making with parental involvement and early surgery (<18 months). CONCLUSION:
      Pediatric urologists are in strong consensus about sex assignment for newborns
      with ambiguous genitalia from CAH, a team approach with parental involvement, and
      early reconstruction. Yet, there is striking variability in attitudes toward sex
      assignment for newborns with 46XY cloacal exstrophy, which should be incorporated
      into the decision-making process with parents.

PMID- 16647403
TI  - Longitudinal changes in bone health as assessed by the speed of sound in very low
      birth weight preterm infants.
AB  - OBJECTIVE: To assess longitudinal changes in speed of sound (SOS) in very low
      birth weight (VLBW) infants and investigate the relationship with markers of
      osteopathy of prematurity (OP) and clinical illness. STUDY DESIGN: Twenty-five
      infants were recruited. Eighteen infants, median gestation 27 weeks (range 24
      32), median birth weight 957 g (range 625-1500 g), had serial scans. SOS was
      measured at both tibiae weekly until 35 to 37 weeks corrected gestational age
      (CGA). RESULTS: Initial median SOS standard deviation score (SDS) (Z) score was 
      0.07 (range-1.3-1.3). SOS correlated with gestation (r, 0.8, P<.005), and birth
      weight (r, 0.67, P<.005.) SOS fell from a median of 2923 m/s (2672-3107) at birth
      to 2802 m/s (2502-2991) at 35 to 37 weeks CGA (P<.05). This fall was greater in
      the 24- to 27-week gestation cohort with a median reduction of 2.2 SDS (1.6, 4.0)
      compared with 1.3 SDS (0.8-2.2) in those>28 weeks (P<.05). There was a negative
      correlation between SOS, at the end of the study, peak serum alkaline phosphatase
      (ALP) (r, 0.6, P<.05), CRIB (Clinical Risk Index for Babies)/CRIB II scores (both
      r, 0.6, P<.05), and duration of total parenteral nutrition (TPN) (r, 0.58,
      P<.05.) CONCLUSIONS: Although tibial SOS was within the expected range at birth,
      there was a subsequent failure to gain SOS, and this was most marked in infants
      of a lower gestation.

PMID- 16647404
TI  - Effect of intravenous pamidronate therapy on functional abilities and level of
      ambulation in children with osteogenesis imperfecta.
AB  - OBJECTIVE: To evaluate the functional abilities and the level of ambulation
      during pamidronate therapy in children with moderate to severe osteogenesis
      imperfecta. STUDY DESIGN: Functional abilities, ambulation, and grip force were
      assessed in 59 patients (mean age, 6.1 years; range, 0.5-15.7 years; 30 girls)
      during 3 years of pamidronate treatment. Functional skills (mobility and self
      care) were both assessed by using the Pediatric Evaluation of Disability
      Inventory. Ambulation level was assessed by using the modified Bleck score. For
      48 patients, results after 3 years of pamidronate treatment could be matched to
      those of patients with similar age and disease severity who had not received
      pamidronate. RESULTS: Mobility and self-care scores increased during the study
      period (+43% and +30%, respectively). The average ambulation score changed from
      0.8 to 1.9. Maximal isometric grip force increased by 63%. Mobility and
      ambulation scores and grip force measures were significantly higher than in
      patients who had not received pamidronate. The difference in self-care scores did
      not reach significance. CONCLUSION: This study suggests that cyclical pamidronate
      treatment improves mobility, ambulation level, and muscle force in children with
      moderate to severe osteogenesis imperfecta.

PMID- 16647405
TI  - Are activated T cells regulators of bone metabolism in children with Crohn
      disease?
AB  - OBJECTIVES: To test the hypothesis that circulating activated T cells may release
      cytokines that decrease bone turnover in children with Crohn disease. STUDY
      DESIGN: Newly diagnosed Crohn disease and healthy controls of similar age were
      compared for bone age, bone mineral content and density, markers of bone
      remodeling, and serum concentration and in vitro T-cell production of receptor
      activator of nuclear factor kappaB ligand (RANKL), interferon (INF)-gamma, and
      osteoprotegerin (OPG). RESULTS: Newly diagnosed children with Crohn disease
      (n=23) had similar bone mineral density (BMD) z-scores and body mass index as the
      controls (n=40). Biochemical markers of bone remodeling indicated a state of low
      bone turnover in the Crohn disease patients compared with controls. Serum OPG
      (pmol/L; mean+/-SD, median) was higher (4.24+/-1.74, 3.98 vs 3.38+/-0.83, 3.41;
      P<.05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50+/
      0.86, 0.28 vs 1.02+/-1.63, 0.49; P<.01), consistent with decreased bone
      resorption. Activated T cells from Crohn disease patients produced a higher
      concentration of INF-gamma (ng/microg protein) than those from controls (20.03+/
      26.39, 8.70 vs 9.76+/-14.10, 6.17; P<.05). CONCLUSIONS: The newly diagnosed
      children with Crohn disease exhibited reduced bone remodeling, possibly due to T
      cell INF-gamma and OPG.

PMID- 16647406
TI  - A multicenter study of the outcome of biliary atresia in the United States, 1997
      to 2000.
AB  - OBJECTIVE: To determine the prognostic factors and optimal approaches to the
      diagnosis and management of biliary atresia, the leading indication for liver
      transplantation in children. STUDY DESIGN: A retrospective study was performed of
      all children who underwent hepatoportoenterostomy (HPE) for biliary atresia
      between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months
      was correlated with demographic and clinical parameters. RESULTS: A total of 104
      children underwent HPE; 25% had congenital anomalies, and outcome was worse in
      those with biliary atresia splenic malformation syndrome. Diagnostic and clinical
      approaches varied, although specific approaches did not appear to correlate with
      outcome. The average age at referral was 53 days, and the average age at HPE was
      61 days. At age 24 months, 58 children were alive with their native liver, 42 had
      undergone liver transplantation (37 alive, 5 dead), and 4 had died without
      undergoing transplantation. Kaplan-Meier analysis of survival without liver
      transplantation revealed markedly improved survival in children with total
      bilirubin level<2 mg/dL at 3 months after HPE (84% vs 16%; P<.0001). CONCLUSIONS:
      Outcome in the study centers was equivalent to that reported in other countries.
      Total bilirubin in early follow-up after HPE was highly predictive of outcome.
      Efforts to improve bile flow after HPE may lead to improved outcome in children
      with biliary atresia.

PMID- 16647407
TI  - High prevalence of renal dysfunction in long-term survivors after pediatric liver
      transplantation.
AB  - OBJECTIVE: To determine the prevalence and identify variables associated with
      renal dysfunction in long-term survivors of pediatric liver transplantation.
      STUDY DESIGN: Data from 117 patients who survived>or=3 years after liver
      transplantation were analyzed. Demographic and clinical information was obtained
      from chart review and from a clinical care database. The dependent variable was
      renal function as determined by measured glomerular filtration rate (mGFR).
      Univariate and multivariate analyses were performed to identify independent
      variables associated with renal dysfunction (mGFR<70 mL/min per 1.73 m2).
      RESULTS: The average time since liver transplant was 7.6+/-3.4 years (range, 3 to
      14.6 years). When the last available mGFR for all patients was analyzed, renal
      dysfunction was present in 32%. In the univariate analysis, mGFR at 1 year after
      transplant, cyclosporine immunosuppression, and time since transplant were
      significant; the second two were strongly collinear. Using multiple logistic
      regression modeling excluding time since transplant, cyclosporine and mGFR at 1
      year after transplant were strongly associated with renal dysfunction.
      CONCLUSIONS: Renal dysfunction is a common complication in children who survive
      liver transplantation. Our observations are of critical importance because
      children may live long enough to move from a stage of renal insufficiency
      characterized by asymptomatic decreased GFR to symptomatic end-stage renal
      disease.

PMID- 16647408
TI  - Mixing rapid-acting insulin analogues with insulin glargine in children with type
      1 diabetes mellitus.
AB  - OBJECTIVE: To determine whether mixing insulin glargine (IG) with a rapid-acting
      insulin (RAI) analogue in the same syringe had any deleterious effects on
      glycemic control in children with type 1 diabetes mellitus. STUDY DESIGN: Data
      from 55 children mixing the IG with a RAI analogue was collected for 6 months
      before and 6 months after the insulin mixing began. Data from a control group of
      55 children not mixing the insulins was collected at similar intervals.
      Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe
      and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and
      blood glucose distribution patterns. RESULTS: After 6 months of study, HbA1c
      values were equivalent for the control and test groups (8.54+/-1.14 vs 8.61+/
      1.14, respectively; P=1.0000). Percentages of blood glucose values in, above, and
      below the target range did not vary significantly in the groups. There were no
      significant differences in the groups in the occurrence of non-severe or severe
      hypoglycemic events or of DKA events. CONCLUSION: There were no significant
      differences in glycemic control between children who mixed IG in the same syringe
      with a RAI analogue compared with children who took separate injections.

PMID- 16647410
TI  - Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy
      in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of
      age, and cause.
AB  - OBJECTIVES: To determine the dosage and factors influencing efficacy of
      adrenocorticotropic hormone (ACTH) for West syndrome. STUDY DESIGN: A
      retrospective study of 135 patients receiving ACTH therapy with a synthetic
      analogue for initial effect, seizure outcome 1 year after therapy, and adverse
      effects. Efficacy and adverse effects were compared among the groups divided by
      clinical factors: dosage, treatment lag, onset age, and cause. RESULTS: One
      hundred thirteen patients had seizure control with ACTH. For more than 1 year
      after ACTH, 59 remained seizure free. Adverse effects were observed in 57, and
      ACTH therapy was discontinued in 23. The lowest dosage group (0.0125 mg/kg/d) had
      fewer episodes of discontinuation (P<.05), whereas differences in efficacy
      between different dosages were insignificant. None of the clinical factors
      correlated with initial effect. The earlier-onset group (<4 months) showed
      unfavorable seizure outcome 1 year after ACTH (P<.01). The cryptogenic patients
      showed better seizure outcome (P<.05) compared with the symptomatic. CONCLUSION:
      Synthetic ACTH therapy at a lower dosage is as effective as natural ACTH therapy
      at a higher dosage. Considering the adverse effects and the benefits for seizure
      control, the ACTH dosage of 0.0125 mg/kg/d (synthetic analogue) is more favorable
      than larger dosage.

PMID- 16647411
TI  - Single dose of anti-D immune globulin at 75 microg/kg is as effective as
      intravenous immune globulin at rapidly raising the platelet count in newly
      diagnosed immune thrombocytopenic purpura in children.
AB  - OBJECTIVE: To conduct a randomized prospective trial of immune globulin treatment
      for 105 Rh+ children with newly-diagnosed immune thrombocytopenic purpura and a
      platelet count<20,000/microL, to determine whether anti-D immune globulin (anti
      D) is as effective as intravenous immune globulin (IVIg). STUDY DESIGN: Eligible
      patients received either a single intravenous dose of 50 microg/kg anti-D (anti
      D50), 75 microg/kg anti-D, (anti-D75), or 0.8 g/kg IVIg, (IVIg). Patients were
      monitored for response to treatment and adverse events. RESULTS: By 24 hours
      after treatment 50%, 72%, and 77% of patients in the anti-D50, anti-D75, and IVIg
      groups, respectively, had achieved a platelet count>20,000/microL (P=.03). By day
      7, hemoglobin concentrations decreased by 1.6 g/dL, 2 g/dL, and 0.3 g/dL in the
      anti-D50, anti-D75, and IVIg groups, respectively. Headache, fever, or chills
      occurred least often in the anti-D50 group. CONCLUSIONS: A single 75 microg/kg
      dose of Anti-D raised the platelet count in children with newly diagnosed immune
      thrombocytopenic purpura more rapidly than standard-dose anti-D and as
      effectively as IVIg, with an acceptable safety profile.

PMID- 16647412
TI  - Plant stanols do not restore endothelial function in pre-pubertal children with
      familial hypercholesterolemia despite reduction of low-density lipoprotein
      cholesterol levels.
AB  - OBJECTIVE: To examine the effect of plant stanols on lipids and endothelial
      function in pre-pubertal children with familial hypercholesterolemia (FH). STUDY
      DESIGN: Children with FH (n=42), aged 7-12 years, were enrolled in a double-blind
      crossover trial, in which they consumed 500 mL of a low-fat yogurt enriched with
      2.0 g of plant stanols and 500 mL of a low-fat placebo yogurt for 4 weeks,
      separated by a 6-week washout period. Lipid profiles and endothelial function
      were assessed after both consumption periods. Endothelial function was measured
      as flow-mediated dilation (FMD) of the brachial artery. RESULTS: This daily
      intake of 2.0 g of stanols significantly decreased the levels of total
      cholesterol (TC) by 7.5% and low-density lipoprotein cholesterol (LDL-C) by 9.2%
      as compared with placebo. High-density lipoprotein cholesterol and triglyceride
      levels remained unaltered. The reduction of LDL-C levels did not improve FMD,
      which was 10.5%+/-5.1% after plant stanol consumption and 10.6%+/-5.0% after
      placebo consumption, respectively (P=.852). CONCLUSION: This study demonstrates
      that plant stanols reduce LDL-C levels in children with FH without improving
      endothelial function.

PMID- 16647414
TI  - A randomized clinical trial of dietary calcium to improve bone accretion in
      children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To examine a behavioral intervention (BI) to increase calcium intake
      in children with juvenile rheumatoid arthritis (JRA) on calcium intake and bone
      mass 6 and 12 months after treatment. STUDY DESIGN: A randomized trial compared a
      6-session BI to a 3-session enhanced standard of care (ESC) with 49 children ages
      4 to 10 years with JRA. Calcium intake was assessed via 3-day diet diaries. Total
      body bone mineral content (BMC), arms and legs BMC, and lumbar spine bone mineral
      density were assessed by dual energy x-ray absorptiometry. RESULTS: BI maintained
      an average calcium intake of 1500 mg/d at 6- and 12-month follow-up. This was
      greater than their baseline level of 972 mg/d, but not greater than the intake of
      1300 mg/day maintained by ESC (P=.09). The BI had a 4% and 2.9% greater gain in
      total body bone mineral content than ESC at 6 and 12 months, respectively
      (P=.005), and a 7.1% and 5.3% greater gain in arms and legs BMC at 6 and 12
      months than ESC (P=.0007). CONCLUSIONS: BI is effective in increasing calcium
      intake and BMC in children with JRA over a 12-month period.

PMID- 16647415
TI  - Quality-of-life in children and adolescents with cystic fibrosis managed in both
      regional outreach and cystic fibrosis center settings in Queensland.
AB  - OBJECTIVES: To assess the health-related quality-of-life (HRQOL) of
      children/adolescents with cystic fibrosis (CF) and compare HRQOL in children
      managed by cystic fibrosis outreach service (CFOS) with those treated in a cystic
      fibrosis center (CFC). To compare HRQOL of children with CF in Queensland with
      previously published HRQOL data from the United States and examine the
      relationship between HRQOL scores and pulmonary function. STUDY DESIGN:
      Participants were children/adolescents with CF and their parents managed by the
      Royal Children's Hospital Queensland at a CFC or CFOS. Two HRQOL surveys were
      used: PedsQL and Cystic Fibrosis Questionnaire (CFQ). RESULTS: There were 91 CFC
      and 71 CFOS participants with similar demographics. PedsQL total summary score
      was statistically higher in CFOS, P=.05. There was no significant difference in
      CFQ scores between groups. Queensland parents reported lower HRQOL for their
      children compared with US parents (P<.01) despite similar pulmonary function.
      Declining pulmonary function correlated with worse CFQ scores in adolescents,
      P<.05. CONCLUSIONS: Children living in regional Queensland reported as good as or
      slightly better HRQOL compared with children attending a CFC. Parent proxy HRQOL
      scores were generally low suggesting a reduced perception of HRQOL by parents for
      their children.

PMID- 16647416
TI  - Variability in asthma severity in pediatric subjects with asthma previously
      receiving short-acting beta2-agonists.
AB  - OBJECTIVE: An analysis of 5 double-blinded, randomized, 12-week asthma trials was
      undertaken to evaluate pediatric subjects (4 to 11 years; n=276) who were
      previously receiving short-acting beta2-agonists alone and subsequently received
      treatment with placebo. At baseline, all subjects met National Asthma Education
      and Prevention Program criteria for moderate/severe asthma. STUDY DESIGN: Asthma
      severity was categorized individually for symptoms, albuterol use, and morning
      peak expiratory flow and then overall taking into account all three parameters.
      RESULTS: Subjects spent the majority of weeks (55%) in the moderate/severe
      category. Subjects spent approximately 48%, 31%, and 22% of weeks in
      intermittent, mild, and moderate/severe categories and 57%, 27%, and 15% of
      weeks, respectively, based on asthma symptoms and albuterol use. Subjects spent
      approximately 62%, 31%, and 8% of weeks in intermittent/mild, moderate, and
      severe categories, based on peak expiratory flow; however, >35% of subjects
      exhibited >or=15 changes in asthma severity classification, based on peak
      expiratory flow. CONCLUSIONS: Asthma is a disease with varying symptomatology,
      and pediatric subjects frequently move between severity categories, especially in
      children with inadequate asthma control. These data also emphasize that asthma
      severity cannot be determined in many pediatric subjects by discrete, point-in
      time assessments of lung function, albuterol use, or asthma symptoms. Failure to
      recognize this problem may contribute to underestimation of disease severity in
      pediatric subjects.

PMID- 16647417
TI  - Childhood pregnancy (10-14 years old) and risk of stillbirth in singletons and
      twins.
AB  - OBJECTIVE: To clarify the association between childhood pregnancy and risk of
      stillbirth. STUDY DESIGN: We analyzed singleton and twin pregnancies that
      occurred in children (10-14 years old) in the United States from 1989 to 2000. We
      estimated the absolute and relative risks of stillbirth by using 15- to19-year
      old and 20- to 24-year-old mothers as comparison groups. RESULTS: The analysis
      involved 17.8 million singletons and 337,904 individual twins. The rate of
      stillbirth was highest in pediatric mothers for both singletons (12.8/1000) and
      twins (56/1000) compared with adolescent (6.8/1000 in singletons and 29/1000 in
      twins) and mature (5.5/1000 in singletons and 20/1000 in twins) mothers. After
      adjusting for confounding characteristics, pediatric mothers continued to exhibit
      significantly elevated risk for stillbirth in both singletons (odds ratio, 1.57;
      95%CI, 1.49-1.66) and twins (odds ratio, 1.97; 95%CI, 1.42-2.73). Preterm birth
      rather than small size for gestational age was revealed by means of sequential
      modeling to account for the excess risk of stillbirth observed in pediatric
      gravidas. CONCLUSION: Pregnancy in childhood is a risk factor for stillbirth;
      shortened gestation rather than reduction in fetal growth is the mediating
      pathway.

PMID- 16647418
TI  - Risky behaviors among motorcycling adolescents in Italy.
AB  - OBJECTIVE: To investigate the relationship between risky behaviors and
      motorcycling in adolescents in Italy. STUDY DESIGN: A questionnaire was
      administered to a random sample of 1000 adolescents attending randomly selected
      public secondary schools to assess personal characteristics and lifestyle;
      motorcycle and helmet use; behavior while driving a motorcycle; traffic-related
      accidents, and receipt of tickets. RESULTS: Of the 894 responders, 54% and 29.2%
      routinely use the helmet as driver or passenger, respectively. Routine helmet use
      was higher among males, current smokers, alcohol drinkers, and those who reported
      that at least one close friend used a helmet. Motorcycling after consuming
      alcohol was higher in males, in current smokers, and in those who used cell
      phones and were tired while driving. An accident in the past year occurred in
      25.7% of riders and was significantly higher in those who used cell phones while
      driving and in those who were interested in learning about motorcycle use.
      Adolescents who reported always motorcycling over the speed limit were at lower
      risk of smoking, talking with the passenger, and using a cell phone while
      driving. Being male, being older, learning about motorcycle use from someone
      outside the family, talking with a passenger, and using a cell phone while
      driving increased the risk of receiving a ticket. CONCLUSIONS: Educational
      programs, legislative measures, and policies to reduce risk behaviors in
      adolescents who use motorcycles are needed.

PMID- 16647419
TI  - Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized,
      double-blind, placebo-controlled, multinational study of recombinant human N
      acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and
      follow-on, open-label extension study.
AB  - OBJECTIVE: The objective of this Phase 3 study was to confirm the efficacy and
      safety of recombinant human arylsulfatase B (rhASB) treatment of
      mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal
      lysosomal storage disease with no effective treatment. STUDY DESIGN: Thirty-nine
      patients with MPS VI were evaluated in a randomized, double-blind, placebo
      controlled, multicenter, multinational study for 24 weeks. The primary efficacy
      variable was the distance walked in a 12-minute walk test (12MWT), whereas the
      secondary efficacy variables were the number of stairs climbed in a 3-minute
      stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion.
      All patients received drug in an open-label extension period for an additional 24
      weeks. RESULTS: After 24 weeks, patients receiving rhASB walked on average 92
      meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC
      (p=.053) than patients receiving placebo. Continued improvement was observed
      during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with
      rhASB than placebo (p<.001). Infusions were generally safe and well tolerated.
      Patients exposed to drug experienced positive clinical benefit despite the
      presence of antibody to the protein. CONCLUSION: rhASB significantly improves
      endurance, reduces GAG, and has an acceptable safety profile.

PMID- 16647420
TI  - Malignant hypertension, polycythemia, and paragangliomas.

PMID- 16647421
TI  - Delayed separation of the umbilical cord in two siblings with Interleukin-1
      receptor-associated kinase 4 deficiency: rapid screening by flow cytometer.
AB  - We describe 2 siblings who had interleukin-1 receptor-associated kinase 4
      deficiency with a novel mutation in exon 2. They had delayed separation of the
      umbilical cord. The flow cytometric analysis of monocytic intracellular tumor
      necrosis factor-alpha production in response to lipopolysaccharide may be a
      useful method to screen for the disease.

PMID- 16647422
TI  - Autosomal recessive interleukin-1 receptor-associated kinase 4 deficiency in
      fourth-degree relatives.
AB  - We report a kindred with autosomal recessive interleukin-1 receptor-associated
      kinase 4 (IRAK-4) deficiency in 3 fourth-degree relatives. A diagnosis of IRAK-4
      deficiency should be considered in families with invasive bacterial disease, even
      if the individuals affected are only distantly related, which falsely suggests
      multigenic or dominant inheritance with low penetrance.

PMID- 16647423
TI  - Neonatal hypoglycemia and occipital cerebral injury.
AB  - Occipital brain injury associated with neonatal hypoglycemia can result in long
      term disability, epilepsy, and visual impairment. The etiology of this pattern of
      injury is unclear; however, transient hyperinsulinism may be an independent risk
      factor. Magnetic resonance brain imaging can delineate the extent of brain injury
      and guide follow-up.

PMID- 16647424
TI  - Vitamin E status in children with cystic fibrosis and pancreatic insufficiency.
AB  - Vitamin E status was compared in 69 children (7.0-10.0 years) with cystic
      fibrosis and pancreatic with the National Health and Nutrition Examination Survey
      III sample (6.0-11.9 years). With median vitamin E intakes of 6 mg/day (dietary)
      and 224 mg/day (supplemental), children with cystic fibrosis had higher serum
      alpha-tocopherol:cholesterol ratios, higher alpha-tocopherol, and lower
      cholesterol levels than in the National Health and Nutrition Examination Survey.

PMID- 16647425
TI  - Reassurance can hurt: parental behavior and painful medical procedures.

PMID- 16647426
TI  - Noncompaction of the ventricular myocardium.

PMID- 16647427
TI  - Natural killer cell deficiencies and severe varicella infection.

PMID- 16647428
TI  - Natural killer cell deficiencies and severe varicella infection.

PMID- 16647429
TI  - Oxygen and oxygenation in the delivery room.

PMID- 16647431
TI  - Validity of HOMA-IR as index of insulin resistance in obesity.

PMID- 16647432
TI  - Clonidine exposures, not toxicity.

PMID- 16647435
TI  - Living donor kidney transplantation from the elderly donor.
AB  - PURPOSE: The organ shortage has led to increasing acceptance of living donation
      in all transplant centers. Although the risk of impaired long-term outcome seems
      to be greater using elderly donors, these organs are not generally refused for
      transplantation. We report our experience with 25 living donor kidney
      transplantations from donors older than 60 years. METHODS: Between 1995 and 2004,
      124 living donor procedures were performed in our center from 83 related and 41
      unrelated donors. Twenty-five donors (19 female, 6 male) were 60 years or older
      (mean, 65.3 +/- 3.9 years). The recipient included (10 females and 15 males)
      showed a higher degree of variance in age (46.1 +/- 14.6 years). The
      immunosuppressive protocol was cyclosporine (CyA)-based regimen in related cases
      and tacrolimus-based in unrelated cases. RESULTS: We transplanted 16 left and 9
      right kidneys from older donors. The mean cold ischemia time was 171 +/- 64
      minutes with a second warm ischemia time of 24 +/- 6 minutes. Severe
      arteriosclerosis made vascular reconstruction by graft interposition necessary in
      two recipients. The acute rejection rate was 20%. Two patients (8%) required
      dialysis in the early postoperative course, whereas initial function was
      excellent in 22 patients (88%). The mean serum creatinine concentration after 12
      months was 1.6 +/- 0.3 mg/dL (n = 24) and 2.0 +/- 0.7 mg/dL (n = 16) at 4 years.
      In comparison, the mean creatinine concentration after 4 years in donors under 60
      years was 1.6 +/- 0.9 mg/dL. Our analysis showed no significant difference in
      long-term graft function comparing young versus old donors in the setting of
      living donor transplants. CONCLUSION: Using living donors older than 60 years for
      transplantation is a feasible and safe option. The difference in long-term
      creatinine between young and old donors was not significant.

PMID- 16647436
TI  - Living kidney donation: anemia and inflammation in the early postoperative
      period.
AB  - Studies on living donor kidney transplantation primarily address the recipients;
      few publications focus on kidney donors. The aim of the present study was to
      detect changes in and compensations of defined parameters of anemia and
      inflammation in the immediate postnephrectomy period. We included six living
      kidney donors who underwent an open anterior-extraperitoneal nephrectomy. We
      excluded donors with complications, such as significant blood loss or infection.
      Blood samples were taken before nephrectomy as well as on postoperative days 1,
      3, 5, and 7, and at discharge for measurements of hemoglobin (Hb), serum
      erythropoietin (Epo), reticulocytes (Reti), pentraxin 3 (PTX3), and C-reactive
      protein (CRP). There was a significant decrease in Hb (>3 g/dL), reaching a
      maximum on day 3 followed by a significant threefold increase in Epo levels on
      day 5 and a nonsignificant elevation of Reti count. CRP increased approximately
      80-fold on day 3. PTX3 showed a similar course, peaking on day 3 with an
      approximate 70-fold increase. After living donor nephrectomy, there was an
      unexpectedly pronounced inflammatory reaction in the absence of any signs of
      bacterial infection simultaneous with a significant decrease in Hb. These
      parameters improved during the hospital stay, in some cases they achieved the
      prenephrectomy level at discharge. These data may assist in interpreting
      laboratory results after nephrectomy among living kidney donors.

PMID- 16647437
TI  - Kidney transplantation using donors with history of diabetes and hypertension.
AB  - PURPOSE: Due to the persistant organ shortage for kidney transplantation, donor
      selection has changed in the past years. Although hypertension and diabetes
      mellitus are known to be risk factors for renal insufficiency, kidneys from
      donors with these diagnoses in their history have been accepted for kidney
      transplantation even with an increased risk of poor graft function. Herein we
      have reported our experience with kidney transplantation using grafts from donors
      with both, a history of type II diabetes and hypertension. METHODS: Between 2000
      and 2005, ten patients were grafted using donors with history of type II diabetes
      mellitus and hypertension. Mean donor age was 58 +/- 7.5 years and recipient age,
      52.2 +/- 15.7 years. Mean HLA mismatch was 0.8 (A); 1.2 (B) and 0.9 (DR). Cold
      ischemia time was 17.4 +/- 4.1 hours. Immunosuppression was based on CyA (n = 7),
      tacrolimus (n = 2) or sirolimus (n = 1). RESULTS: Six patients (60%) showed good
      initial function, and four (40%) had delayed graft function (DGF). One patient
      died at ten weeks due to multiorgan failure. Two (20%) biopsy-proven rejections
      were diagnosed, one of which was resistant to therapy. Six months after kidney
      transplantation, 7 (77%, n = 9) showed good graft function (creatinine 1.3 to 2.4
      mg/dL), but one patient displayed long-lasting DGF with poor function.
      CONCLUSION: Grafts from donors with a history of diabetes mellitus and
      hypertension are suitable for kidney transplantation. Elevated rate of DGF (40%)
      would justify allocation of these organs to local transplant centers to shorten
      ischemia time and thereby reduce DGF and achieve better long-term results.
      Identification and detailed evaluation of these donors prior to allocation (eg,
      HbAlc, biopsy) may help transplant centers to accept these kidneys.

PMID- 16647438
TI  - Routine screening of donor hearts by coronary angiography is feasible.
AB  - BACKGROUND: Because of the shortage of donor hearts, the criteria for acceptance
      have been considerably extended. Meanwhile every fourth heart donor in Europe is
      over 50 years old. As we have previously demonstrated, transmission of
      preexisting coronary atherosclerosis (CAS) by means of transplantation is not
      rare. Transmitted CAS results in a 2- to 3-fold increased risk for early graft
      failure after heart transplantation (HTX). Nevertheless, in most cases donor
      angiograms are not considered feasible. METHODS: In May 2003 in the northeast
      region of the Deutsche Stiftung Organtransplantation (DSO-NO), we introduced the
      guideline that every donor over 40 years old must be screened by angiography.
      RESULTS: Up to May 2003, fewer than 5% of donors had been screened by
      angiography; this situation is the rule in most Eurotransplant regions at
      present. Since May 2003 in the DSO-NO region, 85% of all donors over 40 years old
      were screened by angiography. Seventy percent of all donor hospitals--offering
      90% of all donors--had an angiography facility. The additional costs of
      approximately euro 800 per donor angiogram were compensated by fewer fruitless
      airplane missions when CAS was diagnosed by the surgeon on the spot, which cost
      on average about euro 5,000 each. In conclusion, from a logistical as well as
      from a financial point of view, almost comprehensive angiographic donor screening
      is feasible. It reduces the risk of a recipient suffering from early graft
      failure.

PMID- 16647439
TI  - Does contrast medium administration in organ donors affect early kidney graft
      function?
AB  - Since the upper age for organ donors has been raised, a higher incidence of
      preexistent organ damage and functional impairment is to be expected. Coronary
      artery sclerosis increases with age. It can only be diagnosed with certainty by
      coronary angiography. Since contrast medium administration may cause renal damage
      when risk factors are present, this study sought to establish whether angiography
      negatively influenced the early postoperative function of kidney grafts. We
      compared the clinical courses of 36 recipients of kidneys from donors in whom
      coronary angiography or levography had been performed with 36 recipients of
      kidneys from donors who had not been subjected to contrast medium. The results
      showed that the administration of contrast medium had no influence on renal
      function at 3 or 6 months after transplantation. In conclusion, fears that donor
      kidneys might be harmed by contrast medium appeared to therefore be unfounded.

PMID- 16647440
TI  - Renal ischemia-reperfusion injury: new implications of dendritic cell-endothelial
      cell interactions.
AB  - In renal ischemia/reperfusion (I/R) injury endothelial cells are a main target.
      The disturbance of endothelial cell physiology leads to endothelial swelling and
      narrowing of the blood vessel lumen. We attribute this effect to impairment of
      endothelial cell nitric oxide synthase (NOS). NO is significantly reduced in the
      course of hypoxia causing dysfunction of the vascular smooth muscle tone.
      Subsequently to an I/R injury, the inflammatory response results in endothelial
      activation with enhanced dendritic cell (DC) adhesion and migration. Thus,
      alloreactive leukocytes are recruited to the inflammatory site. Finally,
      dendritic cell-endothelial cell interactions may play a crucial role in antigen
      specific allograft rejection in I/R renal injury. DCs, which activate naive
      alloreactive T cells, play a central role in the establishment of alloantigen
      specific immunity. In the course of hypoxia rejection is initiated at the
      activated layer of foreign endothelial cells (EC), which forms an immunogenic
      barrier for migrating DCs and T cells. Host DCs that bind to postischemic
      activated ECs invade the allografted tissues, or remain stationary in the
      subendothelial layer, or transmigrate into lymphoid vessels and secondary
      lymphoid organs, where they present alloantigens to naive host T cells. Organ
      rejection is mediated by host alloreactive T cells, which are activated by donor
      DCs (direct activation) or host DCs (indirect activation). We hypothesized that
      DC-EC binding and migration is the first step in the renal I/R injury that
      mediates allotransplant rejection. We sought to better understand the downstream
      events of a renal I/R injury by understanding DC binding and migration, thereby
      seeking new strategies for more specific immunomodulatory interventions. Herein
      we developed a new allotransplant-rejection model after renal I/R injury.

PMID- 16647441
TI  - Formation of ascorbate radicals as a measure of oxidative stress: an in vitro
      electron spin resonance-study using 2,2-Azobis (2-amidinopropane) dihydrochloride
      as a radical generator.
AB  - Reactive oxygen species (ROS) are continuously formed in biological systems. Any
      increase in radical production or decrease in the defense against ROS induces
      oxidative stress. This imbalance between ROS formation and ROS detoxification is
      believed to be involved in a variety of pathogenic processes, including ischemia
      reperfusion injury. Various markers indicating oxidative stress has been used in
      experimental and clinical studies. One of them is ascorbate free radical (AFR),
      electron spin resonance intensity of which correlates with the severity of
      radical formation. We investigated the impact of alkyl peroxyl radicals produced
      by 2,2-Azobis (2-amidinopropane) dihydrochloride decomposition on the magnitude
      of the AFR signal. Our data confirmed the principal applicability of AFR as a
      nontoxic marker of radical generation.

PMID- 16647442
TI  - FTY720 for treatment of ischemia-reperfusion injury following complete renal
      ischemia in C57/BL6 mice.
AB  - BACKGROUND: Organ dysfunction followed by single-organ or even multiorgan failure
      due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart
      transplantation. Various approaches had been attempted to prevent this I/RI. One
      is the administration of FTY720, a synthetic structural analogue of sphingosine,
      which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of
      this study was to evaluate the effect of intraoperative FTY720 administration
      following controlled bilateral kidney ischemia in comparison to steroid or
      placebo application. METHODS: Male c57BL6/J mice (n = 115; body weight 25 to 30
      g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution.
      Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours.
      At termination all surviving animals were sacrificed. RESULTS: Following 30
      minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed
      significant protective effects on long-term survival after controlled bilateral
      warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a
      significant T-lymphocyte depletion in peripheral blood after FTY720 treatment,
      which was not observed after steroid or vehicle treatment. CONCLUSION: The
      improved long-term survival shown in this study might be due to a protective
      effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte
      depletion shown in the FACS analysis.

PMID- 16647443
TI  - Realization of the sixth modification of guidelines for organ placement in renal
      transplantation-a single-center experience.
AB  - Because of the recommendation of the standing commission on organ
      transplantation, the Board of Bundesarztekammer agreed to a modification of the
      guidelines for organ transplantation under section 16 of the transplantation law
      regarding organs from extended donors who have grave diseases. In our case all
      patients on our waiting list were contacted to be informed about the guideline
      changes. Only 6 of 322 patients (1.9%) on our waiting list who were
      transplantable agreed to allow organ placement from a donor with extended
      criteria.

PMID- 16647444
TI  - Living related kidney donation as an advantage for growth of children independent
      of glomerular filtration rate.
AB  - Seventy-two pediatric kidney recipients of living related donors (LRD) and 145 of
      cadaveric donors (CAD) were analyzed for height standard deviation scores (Ht
      SDS) and glomerular filtration rates (GFR) directly after transplantation and
      over the following 5 years. GFR was significantly higher immediately after
      transplantation in LRD compared with CAD recipients; however, GFR was not
      different during the 5-year follow-up period. Although Ht-SDS was comparable at
      the time of transplantation in both groups, it was significantly higher among LRD
      recipients over the next 5 years. Multivariate and covariate analyses showed that
      Ht-SDS after 5 years was mainly influenced only by CAD vs LRD and not by GFR or
      other factors, namely, donor age, rejections, time of dialysis, preemptive
      transplantation, age at transplantation, or immunosuppression. Thus, children
      receiving grafts from LRD showed a better catch-up growth independent of the GFR
      than those after CAD transplantation. We concluded that the period of donor death
      and prolonged cold ischemia in CAD grafts may lead to changes in gene expression
      of cytokines and other mediator molecules that affect bone metabolism. Better
      growth seems to be an additional factor supporting the policy of LRD kidney
      transplantation as the best option in children.

PMID- 16647445
TI  - Successful renal transplantation in a child with thrombosis of the inferior vena
      cava and both iliac veins.
AB  - An 8-year-old girl who was born premature in the 24th gestational week suffered a
      septic venous thrombosis due to an indwelling central line during the early
      perinatal period. As a result the inferior vena cava including the intrahepatic
      segment and both iliac veins was obliterated. The right kidney was primarily
      dysplastic, and the left kidney developed a partial infarction. Renal function
      was compensated until the age of 6 years. Magnetic resonance angiography at that
      time showed a collateral system via the azygos vein. The venous pressure and its
      variation with breathing as measured invasively showed normal values. During
      pretransplant initiation of immunosuppressive therapy, the child developed
      cerebral convulsions after the third dose of cyclosporine. Therefore we utilized
      a regimen of rapamycin, mycophenolate mofetil, and steroids. The transplantation
      was performed using a living donor graft from the child's mother. The relatively
      long vein from the left kidney was used for anastomosis with a large presacral
      collateral vein. Twelve months after transplantation the kidney function is
      stable with a serum creatinine of 0.5 mg/dL. The recipient thrombosis of the
      caval and iliac veins is not a principal contraindication for successful renal
      transplantation. MR angiography and invasive pressure measurements facilitated
      evaluation of the collateral venous system. The living donation setting allowed
      the initiation of an immunosuppressive regimen that was tailored to the
      concomitant diseases of the child.

PMID- 16647446
TI  - Reconstruction of ureteral necrosis in kidney transplantation using an ileum
      interposition.
AB  - PURPOSE: Ureteral necrosis is a serious problem in kidney transplantation.
      Sometimes re-ureterocystostomy is possible, while other cases require an
      elaborate reconstruction to maintain kidney function. We report our experience
      with ileum interposition for ureteral reconstruction. METHODS: After 9 years of
      dialysis treatment a 58-year-old patient was grafted using the left kidney of a
      59-year-old donor with a cold ischemic time of 9.5 hours. The early postoperative
      course was uneventful apart from delayed graft function. Immunosuppression
      consisted of an IL-2-receptor antibody, calcineurin inhibitor, mycophenolate
      mofetil, and corticosteroids. Discharge serum creatinine was 2.3 mg/dL. In month
      4 the patient showed a pararenal urinoma; cystoscopy revealed necrosis of the
      distal ureter. Operative revision showed urine leakage from the renal pelvis
      through the urinoma into the bladder. As the whole ureter was necrotic, a re
      ureterocystostomy was not possible. The patient's own ureter had been extirpated,
      and the bladder was too small to do a direct anastomosis between it and the
      kidney. Consequently, an ileum interposition was performed. RESULTS: The
      postoperative course was uneventful. Kidney function was stable with a nadir
      creatinine concentration of 2.0 mg/dL 18 months' posttransplantation, and 14
      months' post ileal interposition the kidney function was still satisfactory, with
      a creatinine level of 2.0 mg/dL. CONCLUSION: Ureteral necrosis is a serious
      complication following kidney transplantation. Whenever a re-ureterocystostomy or
      an uretero-ureterostomy is not possible, the interposition of the ileal segment
      represented a safe procedure to deal with this problem.

PMID- 16647447
TI  - Unusual manifestation of posttransplant lymphoproliferative disorder in the
      esophagus.
AB  - Early manifestations of posttransplant lymphoproliferative disorders (PTLD) are
      mainly associated with a primary Epstein-Barr virus (EBV) infection. Rapid
      increases in peripheral blood EBV DNA load are supposed to reliably predict PTLD.
      We report a boy who 6 months after living-related kidney transplantation
      presented with an extranodal esophageal manifestation of PTLD. Despite a primary
      EBV infection with tonsillitis, the peripheral blood EBV DNA remained low, hiding
      the progression to PTLD.

PMID- 16647448
TI  - Pretransplant calcium levels have no predictive value for delayed graft function,
      long-term graft function, cardiovascular events, or graft and patient survival in
      renal transplantation.
AB  - BACKGROUND: Disorders of calcium homeostasis are one of the most common problems
      in patients with end-stage renal disease (ESRD). Elevated calcium levels increase
      the incidence of cardiovascular mortality in ESRD patients, and appear to be a
      risk factor for the occurrence of delayed graft function (DGF) after kidney
      transplantation. Therefore, we investigated the impact of pretransplant serum
      calcium levels on outcomes after kidney transplantation: DGF, acute rejection,
      graft function, and survival, as well as the incidence of cardiovascular events.
      METHODS: We studied 285 patients (96.9% of all transplanted patients) who
      underwent their first transplantation between 1995 and 2004. Demographic data
      were extracted from hospital records or were documented during follow-up; serum
      samples were collected at the time of transplantation. RESULTS: In our cohort the
      incidence of DGF was 16.5% and 35.4% of acute rejection episodes (ARE). However,
      pretransplant calcium levels were not related to DGF or ARE in our patient
      cohort. Furthermore, there was no correlation between pretransplant serum calcium
      level with the incidence of cardiovascular events or mortality, as well as graft
      function or survival. CONCLUSION: In our study population pretransplant calcium
      levels showed no effect on DGF, ARE rate, the occurrence of cardiovascular events
      or death, renal graft function, or survival. Therefore, pretransplant calcium
      level is not a helpful marker for risk stratification at the time of
      transplantation.

PMID- 16647449
TI  - Diagnostics and therapy of lymphoceles after kidney transplantation.
AB  - Lymphocele incidence after kidney transplantation is as high as 18%. We
      retrospectively studied the therapy of 42 lymphoceles that occurred in our clinic
      between 1990 and 2005, focusing on possible predisposing factors for their
      formation and the results of several therapy variants: conservative, operative,
      percutaneous puncture, and laparoscopic or open marsupialization. There was no
      connection between lymphocele formation and the following parameters: the extent
      to which the iliac vessels had been prepared, the materials used for the
      preparation, or whether clips or ligatures were applied. Lymphoceles may
      originate either from the lymphatic system of the recipient or the transplanted
      kidney. The most sensible measures to prevent their occurrence therefore seems to
      be to restrict the transplant bed to the smallest permissible level with careful
      ligature of the lymphatic vessels in the area of the kidney hilus. Treatment for
      lymphoceles should start with minimally invasive measures. We use the following
      algorithm in our clinic: puncture to differentiate between urinoma/lymphocele and
      to test for bacterial infection, sclerotization (200 mg doxycyclin), and finally
      marsupialization if persistent. The choice of operative technique depends on the
      location. This algorithm resulted in a relapse rate of 9.5% during the
      postoperative observation period of up to 15 years.

PMID- 16647450
TI  - Use of catheters with the AgION antimicrobial system in kidney transplant
      recipients to reduce infection risk.
AB  - Microbial blood infection represents a high risk for immuno-suppressed patients.
      Of all catheter-related infections in the bloodstream, 90% result from the use of
      central venous catheters, the main cause being microbial colonization at the
      catheter's insertion point or the catheter hub. Between January 2003 and December
      2004, 102 patients received a renal transplant including 57 who received a triple
      lumen central venous catheter (CVC) during the procedure. Two catheters were
      used: a standard polyurethane catheter placed in the jugular veina or the
      subclavian veina for group I, and polyurethane catheters with the AgION
      antimicrobial system always placed in the subclavian veina for group II. Care and
      maintenance of the CVCs was standardized in both groups. After catheter removal,
      the tips were analyzed microbiologically. Of 57 (43.9%) CVCs, 25 were found to be
      contaminated. In the first group 24 out of 41 CVCs (58.5%) showed bacterial
      growth, whereas in group II only one catheter (6.6%) had a biofilm. The most
      common contaminant (18 out of 25, 72%) was Staphylococcus epidermidis. In group
      II, two patients had positive blood cultures yet a microbiologically sterile CVC.
      None of the catheters with the AgION antimicrobial system had to be removed owing
      to local infection or intolerance. The continuous release of silver ions
      increases the protection against bacteria and fungi during the entire time of
      catheterization. Use of catheters with the AgION antimicrobial system lead to a
      marked reduction in catheter-associated infections of the bloodstream.

PMID- 16647451
TI  - Resolution of sirolimus-induced pneumonitis after conversion to everolimus.
AB  - BACKGROUND: Sirolimus-induced pneumonitis usually requires the complete cessation
      of sirolimus. Herein we have reported five cases of recovery from sirolimus
      pneumonitis after conversion from sirolimus to everolimus. PATIENTS: All five
      cases were comparable with regard to their clinical conditions. The ages were
      between 46 and 64 years. They had received kidney transplants 3 to 18 years
      earlier. In four cases, the reason for sirolimus therapy was toxicity due to
      calcineurin inhibitors on a transplant biopsy; three of the patients also
      displayed malignant tumors: renal cell carcinoma, spinocellular carcinoma, or
      melanoma. Their serum creatinine levels were elevated between 150 and 350
      micromol/L. In all five cases, bronchoscopy disclosed lymphocytic pneumonitis and
      bronchiolitis obliterans. The immunosuppressive co-medications were prednisolone
      in three, azathioprine in one, and mycophenolate mofetil in four cases. The
      previous sirolimus dose was 1 to 4 mg/day, with sirolimus trough levels between 5
      and 12 ng/mL. The patients were switched to everolimus at doses between 1 x 0.25
      and 2 x 0.75 mg/day to achieve trough concentrations between 3 and 8 ng/mL.
      Pulmonary symptoms and radiological findings resolved completely within 1 to 4
      weeks. CONCLUSION: Everolimus is more hydrophilic by virtue of differing from
      sirolimus by one hydroxyl group. Sirolimus-induced pneumonitis improved after
      conversion to everolimus.

PMID- 16647452
TI  - Side effects of sirolimus.
AB  - The mTOR inhibitor sirolimus improves renal transplant function compared with the
      nephrotoxic calcineurin inhibitors. We evaluated retrospectively the adverse
      events in 119 of 134 patients getting sirolimus which seemed to be caused by
      sirolimus. Patients were converted to sirolimus because of malignancies (n = 47),
      a creeping creatinine (n = 33), or hypertension (n = 26). One cohort had started
      sirolimus from the time of transplantation (n = 28). A rise in serum lipids and a
      decrease in hemoglobin were seen relatively regularly, while arthralgia,
      peripheral edema, gastrointestinal complaints, skin disorders, electrolyte
      disturbances, and infections occurred only occasionally. Interestingly, 31% of
      patients developed doubling or more proteinuria. Among renal biopsies, 9/13
      showed a glomerulopathy which in 6 cases was de novo and in 3 cases, a presumed
      recurrence of the primary kidney disease. Thus, we think that caution is
      required, particularly in connection with preexisting glomerular disease.

PMID- 16647453
TI  - Recurrent complicated colon diverticulitis in renal transplanted patient.
AB  - Colon perforation due to diverticulitis is a life-threatening complication in the
      postoperative course of kidney transplantation. In the immunocompromised patient
      a diagnosis of diverticulitis is difficult to make. We report a 53-year-old woman
      being kidney transplanted 14 years ago with known diverticulosis. She was
      admitted with acute severe pain in the lower left abdomen. Abdominal computed
      tomography (CT) scan indicated a diagnosis of intestinal abscess in the small
      pelvis. Laparotomy showed a covered sigma perforation with abscess located in the
      small pelvis (Hinchey-I). Because of the immunocompromised situation of the
      patient we performed a Hartmann procedure. Her postoperative course was
      uneventful. In a 6-month interval the intestinal continuity restoration was
      performed. Twelve days after discharge the patient was readmitted with reduced
      renal function and increased infection parameters. During physical examination
      the abdomen was tender. The patient complained of abdominal pain in the left
      upper abdomen and additional pain in the left shoulder. An antibiotic therapy
      using ciprofloxacin was already initiated owing to a urinary tract infection. An
      abdominal CT scan was performed and indicated an intestinal abscess in the left
      upper abdomen. Laparotomy showed an abscess involving transverse colon, distal
      jejunum, and proximal ileum (Hinchey-II). Segmental resection of the left colonic
      flexure, proximal jejunum, and ileum was performed. The postoperative course was
      uneventful and the patient was discharged on the 8th postoperative day. The
      present casuistry emphasizes that the immunocompromised patient can undergo
      diverticulitis twice, and that primary anastomosis is a feasible option for
      patients with localized peritonitis due to complicated diverticulitis.

PMID- 16647454
TI  - Interventional stenting for ruptured iliac aneurysm following transplant
      nephrectomy.
AB  - Surgical removal of a failed kidney graft may lead to a variety of postoperative
      complications, development of an aneurysm being a relatively rare complication.
      We report the case of a 34-year-old man who developed an iliac aneurysm 13 years
      after transplant nephrectomy. Interventional stenting was performed upon the
      rupture of the aneurysm. Postintervention the function of the contralateral
      transplanted kidney was stable and the patient recovered. An endoleak was
      diagnosed after 1 week, which was also stented. No operative procedure was
      necessary. In conclusion, even in an emergency situation interventional stenting
      of a false iliac aneurysm after transplant nephrectomy may be a therapeutic
      option.

PMID- 16647455
TI  - Acute renal failure after liver transplantation: incidence, etiology, therapy,
      and outcome.
AB  - Acute renal failure (ARF) was a frequent complication after orthotopic liver
      transplantation (OLT) when ARF was defined by a calculated glomerular filtration
      rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the
      first week after OLT. We analyzed 1352 liver transplant recipients in
      retrospective fashion with regard to the incidence, etiology, therapy, and
      outcome of ARF; 162 patients developed ARF within the first week after OLT (12%),
      among whom 157 patients (97%) were recompensated by postoperative day 28.
      Altogether 52 patients (32%) received an average of 6 hemodialysis treatments,
      excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors
      for this complication included hepatorenal syndrome type II, a glomerular
      filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

PMID- 16647456
TI  - Portal hyperperfusion causes disturbance of microcirculation and increased rate
      of hepatocellular apoptosis: investigations in heterotopic rat liver
      transplantation with portal vein arterialization.
AB  - Clinical results of portal vein arterialization (PVA) in liver transplantation
      are controversial. One reason for this is the lack of a standardized flow
      regulation. Our experiments in rats compared PVA with blood-flow regulation to
      PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In
      group I (n = 19), the graft's portal vein was completely arterialized via the
      right renal artery in-stent technique, using a 0.3-mm stent, leading to a
      physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was
      used. In group II, the average portal blood flow after reperfusion was
      significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of
      liver weight; P < .001). The sinusoidal diameter after reperfusion was
      significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/-
      0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was
      significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13
      microm/s). Stasis of erythrocytes occurred; consequently, the functional
      sinusoidal density was significantly reduced in group II (38 +/- 7%) compared
      with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal
      vein, the number of apoptotic hepatocytes was significantly higher in group II
      than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power
      fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9
      grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I,
      only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results
      demonstrate negative effects of portal hyperperfusion in transplanted livers,
      which are correctable by adequate flow regulation.

PMID- 16647457
TI  - Fluorescent microspheres reveal different regional blood flow in hyperacutely
      rejected nontransgenic and hDAF pig hearts.
AB  - Classic features of hyperacute rejection show differential severity in the inner
      compared to the outer myocardium. In the present study, regional blood flow (RBF)
      measured by fluorescent microspheres served as a marker of the extent of
      hyperacute rejection. Using a working heart model, hearts of nontransgenic and
      hDAF transgenic pigs were perfused with human blood. Additionally, hDAF
      transgenic pig hearts were perfused with human blood containing GAS914 or the
      GPIIb/IIIa inhibitor tirofiban. Injections of fluorescent microspheres into the
      donor heart were performed in situ and during perfusion. Reference arterial blood
      samples were collected from the inferior aorta and the afterload line. Perfusion
      was terminated before hyperacutely rejected hearts failed to pump against the
      afterload column. RBF was determined in tissue samples of standardized areas of
      the left atrium and ventricle. Each specimen was divided into subepicardial and
      subendocardial tissue samples. Fluorescence intensity was measured using an
      automated luminescence spectrometer. At the end of perfusion with human blood,
      hyperacutely rejected nontransgenic pig hearts showed a higher RBF in the
      subendocardium. In hDAF-transgenic pig hearts perfused with unmodified human
      blood the subendocardial/subepicardial blood flow ratio changed in favor of the
      subepicardium. This ratio was not further improved by GAS914. In contrast,
      tirofiban was able to assimilate subepicardial and subendocardial blood flow. In
      conclusion, RBF of hyperacutely rejected pig hearts was inhomogeneous. Inhibition
      of complement activation improved the reduced subepicardial RBF, but depletion of
      antibodies had no positive effect. The ability of tirofiban to further increase
      subepicardial RBF affirms thrombosis of subepicardial veins as the defining
      characteristic of hyperacute rejection.

PMID- 16647458
TI  - Emotional stress and subjective body experience of heart transplantation
      candidates.
AB  - We studied subjective complaints, psychological symptoms, and subjective
      appraisal of their body of 54 heart transplantation candidates at the time of
      admission to the waiting list using standardized psychological tests (GBB24, SCL
      90-R, FBeK). The results of GBB24 and SCL90-R indicated high scores of strain
      before transplantation. In the FbeK, patients assessed their own body as worse
      than the normal population on all scales. Male patients displayed significantly
      higher scores of strain than women, but there was no difference in assessing
      their own bodies. The considerable scores of strain indicate the need for
      psychosomatic and psychotherapeutic interventions in a significant subgroup of
      patients.

PMID- 16647459
TI  - Intravital microscopy of pulmonary microcirculation after single lung
      transplantation in pigs.
AB  - BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following
      lung transplantation (LTx). Unfortunately, in vivo observations and quantitative
      analyses of the pulmonary microcirculation following LTx are technically
      demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals.
      The left lung was harvested and preserved using donor aortic vessel segments, the
      pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of
      ischemia, the lungs were transplanted by direct connection of the conduits to the
      left atrial appendage and the left pulmonary artery of the recipient. The lungs
      were placed extrathoracically and ventilated. The recipient left lung was
      excluded. With this procedure, mechanical trauma to the lung and moving artefacts
      were avoided. Intravital microscopic observation became feasible. RESULTS:
      Following reperfusion, oxygenation of pulmonary venous blood was excellent.
      However, blood flow distribution was significantly reduced to the transplanted
      lung compared with the native right recipient lung. Pulmonary vascular resistance
      was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during
      reperfusion compared to a value of 500 for the native right lung. The pulmonary
      microcirculation showed a significant number of no-reflow areas with extremely
      reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm)
      showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to
      be a major pathogenic factor for the development reperfusion failure.
      Quantification of alterations within the microvasculature may shed light on
      various treatment modalities that reduce perfusion failure.

PMID- 16647460
TI  - Tracheal allograft transplantation in rats: the role of different
      immunosuppressants on preservation of respiratory epithelium.
AB  - BACKGROUND: Bronchiolitis obliterans is the most significant complication
      adversely affecting the survival of lung allograft recipients. Injury and loss of
      epithelium are associated with obliteration of the airway lumen. The aim of this
      study was to examine the effects of various immunosuppressants on airway
      epithelium. METHODS: Tracheae from Brown Norway donors were heterotopically
      transplanted into the greater omentum of Lewis (allografts) or Brown Norway
      (isografts) animals. Recipients were treated for 28 days with FK778 (20 mg/kg),
      tacrolimus (4 mg/kg), or sirolimus (2 mg/kg). Tracheal segments were evaluated
      for the degree of luminal occlusion as well as the type and percent of luminal
      epithelial cell coverage. RESULTS: All agents inhibited peritracheal infiltration
      and luminal obliteration. Tacrolimus- more than sirolimus-treated recipients
      showed partial preservation of the luminal epithelial coverage, whereas animals
      that received FK778 showed no respiratory epithelium. The epithelial loss was
      accompanied by the appearance of fibrous tissue, which replaced the mucosa.
      CONCLUSIONS: Tacrolimus as well as sirolimus effectively prevented the
      development of obliterative airway disease whereas tacrolimus and, to a lesser
      degree, sirolimus preserved epithelial cells as a source of protective cytokines.
      With FK778 significant airway obliteration was suppressed despite complete
      epithelial loss. Thus, FK778-treated animals displayed an epithelial-independent
      inhibitory effect on myofibroblast proliferation.

PMID- 16647461
TI  - Evaluation of type 1 diabetics for simultaneous pancreas-kidney transplantation
      with regard to cardiovascular risk.
AB  - The main cause of death for diabetic patients and patients on dialysis is
      coronary artery disease (CAD). The most common cause of graft loss following
      simultaneous pancreas and kidney transplantation (SPK) is death with a
      functioning graft due to CAD. Therefore, careful pretransplantation evaluation of
      CAD is mandatory. In our series, every patient undergoes a noninvasive cardiac
      function test like dobutamine stress echocardiography (DSE) or myocardial
      thallium scintigraphy using adenosine to induce medical stress. Thirty patients
      were evaluated for SPK: 15 patients with myocardial scintigraphy and 8 with DSE.
      Seven investigations showed pathological findings and we performed coronary
      angiograms, none of which showed coronary artery stenosis. Seven primary coronary
      angiograms were performed: four due to a history of CAD and three as a primary
      diagnostic. Following SPK one patient died at 21 days after transplantation due
      to myocardial infarction. He had a history of CAD with angioplasty and stent
      implantation. Noninvasive cardiac function tests like DSE or myocardial
      scintigraphy are reliable methods to evaluate CAD in patients with diabetic
      nephropathy awaiting SPK. In case of a suspicious finding or a history of CAD, a
      coronary angiogram should be performed to assess the need for revascularization.
      Following this algorithm we may further reduce the mortality of SPK.

PMID- 16647462
TI  - Pharmacokinetic profiling of cyclosporine microemulsion during the first 3 weeks
      after simultaneous pancreas-kidney transplantation.
AB  - The optimal effect of therapy with cyclosporine (CsA) seeks to minimize
      undesirable side effects while maximizing immunosuppression. This balance,
      depends on CsA exposure, which may be characterized by the area under the
      concentration-time-curve (AUC). Therefore, we tested the pharmacokinetic profile
      of microemulsion CsA as a superior approach to guide clinical immunosuppression
      after de novo simultaneous pancreas-kidney transplantations. We examined 10
      consecutive pancreas-kidney recipients with type 1 diabetes and end-stage renal
      disease. All patients were treated with a regimen consisting of CsA,
      mycophenolate mofetil (MMF), and prednisone. Full (9-point) pharmacokinetic
      studies (C0, C1, C2, C3, C4, C6, C8, C10, C12) were performed on week 1 and
      during week 3 to examine CsA pharmacokinetic profiles. Mean AUC0-12 of 4431 +/-
      2400 microg x h/L at week 1 remained stable at week 3 (5119 +/- 1190 microg x
      h/L). The C6 sampling time displayed the best correlation with AUC0-12 (r2 =
      0.881), followed by C3 (r2 = 0.758). Our preliminary data after simultaneous
      pancreas-kidney transplantation support the hypothesis that C3 or C6 sampling is
      a more accurate predictor of the AUC0-12 than C0. The combination of two
      samplings, namely C3 + C6 (r2 = 0.938) or C2 + C6 (r2 = 0.955) proved excellent
      prediction of exposure after simultaneous pancreas-kidney transplantation.

PMID- 16647463
TI  - MHC class II-mediated antigen presentation by alloreactive rat CD4+ T cells does
      not induce regulatory properties.
AB  - Activated CD4+ T cells have the capacity to express major histocompatibility
      complex (MHC) class II molecules and to present processed antigens to T cells.
      Because the role of MHC class II positive T cells in allograft rejection is
      unknown, the purpose of this study was to investigate their function as antigen
      presenting cells (APCs) in the allogeneic immune response. For this, alloreactive
      CD4+ T cells were induced in Lewis rats by immunization with the allogeneic
      peptide P1. The P1-specific T cells are involved in the rejection of allografts
      from Wistar Furth rats. With monoclonal antibodies specific for the alphabeta T
      cell receptor (clone R73) and MHC class II molecules (clone Ox6), the presence of
      antigen-specific T cells, with and without expression of MHC class II molecules,
      was demonstrated. Concerning their ability to bind these antibodies they were
      characterized as R73(pos), Ox6(pos) and R73(pos), Ox6(neg), respectively. The
      R73(pos), Ox6(pos) T cells loaded with P1 were indeed very effective in
      restimulating R73(pos), Ox6(neg) T cells but not vice versa. Further on,
      R73(pos), Ox6(pos) T cells, but not R73(pos), Ox6(neg) T cells, were able to
      activate naive allogeneic T cells demonstrating their capacity to express co
      stimulatory molecules. In addition, specific mRNA for CD86, MHC class II, and
      CIITA, the master regulator of MHC class II expression, were detectable in the
      R73(pos), Ox6(pos) T cells only. In conclusion, the R73(pos), Ox6(pos) T cells
      act as professional APCs with the possible biological capability of amplifying
      the local immune response to the allograft.

PMID- 16647464
TI  - FK778: new cellular and molecular mechanisms of action.
AB  - PURPOSE: The new malononitrilamide FK778 is currently being evaluated as an
      immunosuppressant for organ transplantation. Its main mechanism is inhibition of
      a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms
      of action on different cell types involved in acute and chronic allograft
      rejection. METHODS: Purified Brown-Norway rat aortic endothelial cell (EC)
      cultures were pretreated with several concentrations of FK778. Endothelial
      adhesion molecule expression (ICAM-1/VCAM-1) stimulated with TNF-alpha was
      quantified by immunofluorescence. Purified Lewis rat lymphocytes (LC) incubated
      with FK778 were stimulated via TCR/CD28 signals, and CD25 expression was
      quantified using FACS analysis. Uridine addition was used in all assays to
      reverse the pyrimidine synthesis blockade. Lymphocyte-EC interaction was assessed
      by micromanipulator-assisted single-cell adhesion assays. Finally, smooth muscle
      cell (SMC) proliferation and migration was analyzed. Uridine addition was used in
      all assays to reverse the pyrimidine synthesis blockade. RESULTS: TNF-alpha
      stimulation and TCR/CD28 co-stimulation significantly increased EC ICAM-1/VCAM-1
      expression and LC CD25 surface expression, respectively. These effects were dose
      dependently inhibited by FK778 and were not reversed by the addition of uridine.
      FK778 dose-dependently attenuated LC adhesion to allogeneic EC. The dose
      dependent inhibition of SMC proliferation by FK778 was abolished by uridine
      addition, whereas the inhibitory effect on SMC migration was not affected by
      uridine supplementation. CONCLUSIONS: FK778 directly reduced endothelial adhesion
      molecule up-regulation, inhibited lymphocyte activation, and attenuated
      lymphocyte-endothelium interactions, critical early steps in graft rejection.
      These effects were separate from the blockade of pyrimidine synthesis. The
      antiproliferative potency of FK778 on SMC may be an important mechanism to
      inhibit the fibroproliferative lesions of chronic organ rejection.

PMID- 16647465
TI  - Stem cell-derived chondrocytes for regenerative medicine.
AB  - The regenerative capacity of cartilage is limited. Transplantation methods used
      to treat cartilage lesions are based mainly on primary cultures of chondrocytes,
      which dedifferentiate during cultivation in vitro and lose their functional
      properties. Stem cells are considered as an alternative source to generate cells
      for two reasons: first, they can almost indefinitely divide in culture, and
      second, they are able to differentiate into various mature cell types. Herein, we
      asked the question whether chondrocytes could be differentiated from mouse
      embryonic stem (ES) cells to a state suitable for regenerative use. When
      cultivated as embryoid bodies (EBs), murine ES cells differentiate into
      mesenchymal progenitor cells, which progressively develop into mature,
      hypertrophic chondrocytes and transdifferentiate into calcifying cells
      recapitulating all of the cellular processes of chondrogenesis. Chondrocytes
      isolated from EBs exhibit a high regenerative capacity. They dedifferentiate
      initially in culture, but later reexpress stable characteristics of mature
      chondrocytes. However, in cultures of chondrocytes isolated from EBs, additional
      mesenchymal cell types can be observed. Mesenchymal stem (MS) cells from bone
      marrow have already been used in tissue engineering settings. We compared the
      chondrogenic differentiation of MS and ES cells.

PMID- 16647466
TI  - Antiproliferative and overadditive effects of everolimus and mycophenolate
      mofetil in pancreas and lung cancer cells in vitro.
AB  - BACKGROUND: Everolimus inhibits the growth of several tumor cell lines in vitro
      as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits
      growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro
      antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line
      Panc-1 and on a small cell lung cancer cell line ScLc. MATERIALS AND METHODS:
      Cells were cultured under standardized conditions. Everolimus was added in
      increasing doses from 0.005 to 500 microg/mL; MMF was used from 0.05 to 5000
      microg/mL. For co-incubation experiments, we combined everolimus (0.005 microg/mL
      and 0.05 microg/mL) with five concentrations of MMF; and MMF (0.5 microg/mL and 5
      microg/mL) with five concentrations of everolimus. The antiproliferative capacity
      was assessed by a BrdU incorporation assay. RESULTS: Everolimus and MMF inhibited
      BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50%
      inhibition was seen in Panc-1 only at 50 microg/mL everolimus, but in ScLc at 5
      microg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was
      observed at 5 microg/L. In ScLc, 40% inhibition of BrdU incorporation was seen
      only at 50 microg/L MMF. In co-incubation, an effective combination for both Panc
      1 and ScLc was 5 microg/mL MMF with 0.005 microg/mL everolimus resulting in 50%
      inhibition of BrdU incorporation (P < .001). CONCLUSIONS: Everolimus and MMF
      showed dose-dependent antiproliferative effects in tumor cell lines in vitro both
      alone and in combination. The combined use of everolimus and MMF showed supra
      additive effects at concentrations used for therapeutic immunosuppression in
      patients.

PMID- 16647467
TI  - Umbilical cord blood cell transplantation for myocardial regeneration.
AB  - Bone marrow remains the most frequently used source of adult stem cells, but its
      angiogenic and possibly also myogenic potentials are likely to regress with
      increasing donor age and morbidity. Recently, cord blood has been suggested as a
      readily available source for non-embryonic stem cells with high regenerative
      capacity. We first tested the capacity of mononuclear cells obtained from human
      umbilical cord blood (UCB(mn)) to migrate to the heart on IV delivery in NOD/Scid
      mice. As evidenced by the presence of human DNA by PCR analysis, UCB(mn) cells
      migrated to the heart in 50% of the mice with myocardial infarctions, but in none
      of the sham-operated control mice. In UCB(mn) cell-positive injured hearts, the
      infarct size was smaller and capillary density higher in the ischemic myocardium.
      By immunohistology, we observed endothelial cell differentiation of UCB(mn) cells
      in the heart but there was no colocalization of UCB cell-specific antibodies with
      markers of myocyte-type cells. In a second series of experiments, we injected 5 x
      10(5) UCB cells enriched for CD133 directly into the necrotic myocardium of
      NOD/Scid mice. Comparisons were performed with an equivalent number of CD133+
      bone marrow (BM) cells or a sham injection in the respective control groups. Both
      BMCD133+ and UCBCD133+ cells abolished postoperative mortality and improved
      capillary density in the injured myocardium, but only BMCD133+ cells led to a
      detectable improvement in myocardial contractility in vivo. We conclude that
      human UCB cells facilitated neovascularization of ischemic myocardium, but their
      capacity for formation of contractile neotissue needs further investigation.

PMID- 16647469
TI  - Intracranial hypertension in fulminant hepatic failure.

PMID- 16647470
TI  - Cerebral blood flow in fulminant hepatitis.
AB  - Fulminant hepatic failure (FHF) is often complicated with cerebral edema,
      intracranial hypertension, and coma. Cytotoxic and vasogenic factors have been
      recognized in the etiology of cerebral edema. One of the main causes seems to be
      the accumulation of glutamine in astrocytes, which is produced from ammonia and
      the excitatory neurotransmitter glutamate. Ammonia is detoxified within the brain
      in astrocytes, where it increases the osmotic pressure for water. Ammonia-induced
      astrocytic water accumulation seems to act as an integrative trigger for the
      development of intracranial hypertension. While cerebral blood flow is sometimes
      reduced in the first stage of FHF, as compensatory cerebral vasoconstriction to
      reduce mean arterial pressure, it later increases as hyperammonemia decreases
      cerebral arteriolar tone. Despite vasodilation in the systemic and splanchnic
      beds at early stages of the disease, cerebral vessel resistance may increase, so
      that cerebral perfusion pressure may be preserved. When cerebral vascular tone is
      no longer effective in the course of illness, vasodilation gradually develops and
      rapidly becomes poorly responsive to carbon dioxide stimulation, which signifies
      loss of autoregulatory tone and cerebral hyperemia develops. Prolonged excessive
      flow may lead to brain swelling, vasogenic edema, and intracerebral hemorrhage.
      Brain edema further aggravates the critically reduced cerebral perfusion and is
      responsible for the high mortality.

PMID- 16647471
TI  - Neurological complications of liver cirrhosis and orthotopic liver transplant.
AB  - Neurological complications are common in cirrhotic patients with end-stage liver
      failure. They comprise a wide array of etiologies, which may originate before,
      during, or after liver transplantation. The objective of this study was to
      describe the nature of the main neurological complications in patients with end
      stage liver failure. Several toxins including ammonia, manganese, benzodiazepine
      like substances, gamma-aminobutyric acid-like substances, and impaired
      dopaminergic neurotransmission are at the top of the list of candidates for
      hepatic encephalopathy, subclinical encephalopathy, and extrapyramidal signs
      before liver transplantation. Central pontine myelinolysis, cerebrovascular
      autoregulation impairment, and paradoxical cerebral embolism are probably
      responsible for the neurological complications during liver transplantation.
      Neurological complications represented by alterations of mental status, seizures,
      and focal motor deficits have been described after liver transplantation. These
      complications have been attributed to several pathogenetic factors, such as a
      poorly functioning graft, an intracranial hemorrhage, a cerebral infarction, an
      infection, or the toxicity of immunosuppressants.

PMID- 16647472
TI  - Significance of hypoxemia screening in candidates for liver transplantation: our
      experience.
AB  - Hepatopulmonary syndrome (HPS) is recognized as one of the causes of hypoxemia in
      patients with chronic liver disease. This complication is responsible for
      increased mortality and increased perioperative risk in liver transplantation
      candidates. Recent data from the literature suggest extending the screening for
      HPS to all candidates for liver transplantation. The aim of this retrospective
      study was to evaluate the incidence of hypoxemia among a population of patients
      awaiting liver transplantation. Using pulse oximetry as a screening tool for
      hypoxemia, 39 of 198 patients (20%) were hypoxemic. The results of this study
      confirmed the importance of screening for hypoxemia among patients awaiting liver
      transplantation. In these patients, a more accurate evaluation of respiratory
      function should be performed to confirm or exclude the diagnosis of HPS.

PMID- 16647473
TI  - The importance of predicting the prognosis in patients with hepatopulmonary
      syndrome: a simple scoring system.
AB  - Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder, complicating
      hepatic diseases, and is responsible for an increased morbidity and mortality
      among patients awaiting liver transplantation. Nowadays, it is recognized as an
      independent risk factor for death in this patient population. The severity of
      hypoxemia and the advanced stage of the liver dysfunction are determinants for
      the prognosis. Therefore, the possibility to be successful, thus improving
      survival, consists of addressing HPS at an earlier stage, giving more attention
      to moderate evidences of this pathology instead of the severe ones. On the basis
      of scientific evidence, we suggest a simple scoring system to predict prognosis
      among patients with HPS, founded on the integration of two main factors: the
      severity of hepatic disease, expressed as class of Child-Pugh, and the severity
      of the hypoxemia. This model of prognostic evaluation has the objective of
      estimating the additional risk of these patients, thereby avoiding a deleterious
      underestimate of risk and an arbitrariness of management.

PMID- 16647474
TI  - Evaluation of liver function for hepatic resection.
AB  - New limits have been established to decrease mortality and morbidity rates after
      liver resection in cirrhotic and non-cirrhotic patients. Various laboratory data
      and imaging techniques have been used to complement the Child-Pugh score to
      predict liver failure after hepatectomy and to assess functional hepatic reserve.
      The greatest experiences are with the aminopyrine breath test and the galactosyl
      elimination capacity, which are decreased among hepatic failure patients after
      liver resection. However, absence of these changes do not totally exclude it. The
      indocyanine green retention test is the most widely used clearance test.
      Nevertheless, it remains imperfect because it depends both on hepatic blood flow
      and on the functional capacity of the liver. Nuclear imaging of the
      asialoglicoprotein receptors with radiolabelled synthetic asialoglicoproteins
      provides volumetric information as well a functional assessment of the liver. In
      summary, while liver function is complex, a successful liver test to assess
      quantitative functional hepatic reserve still needs to be established. The
      combination of the Child-Pugh score, the presence of ascites, the serum bilirubin
      levels, the indocyanine green retention (ICG R15) value, and the remnant liver CT
      volumetry seems to avoid an index of liver failure after hepatic resection. Cases
      when ICG R15 is above 15% should be combined with portal vein embolization. If
      there is no possibility to perform an ICG clearance test, it may be replaced with
      other available, well known dynamic liver function tests.

PMID- 16647475
TI  - Plasma disappearance rate of indocyanine green in liver dysfunction.
AB  - The presence of hepatic dysfunction significantly affects the length of hospital
      stay and the outcome in critically ill patients. Considering the important
      partial hepatic functions of metabolism, synthesis, detoxification, and
      excretion, the worse clinical course of patients suffering from hepatic
      dysfunction is not surprising. The most often used indicator of hepatic
      dysfunction is bilirubin. However, bilirubin and other commonly used static
      laboratory tests provide only indirect measures of hepatic function. In contrast
      to these static tests, dynamic liver tests, such as indocyanine green (ICG)
      disappearance rate should provide better direct measures of the actual functional
      state of the liver at the time of assessment. The ICG is a water-soluble inert
      compound that is injected intravenously. It mainly binds to albumin in the
      plasma. ICG is then selectively taken up by hepatocytes, independent of adenosine
      triphosphate (ATP), and later excreted unchanged into the bile via an ATP
      dependent transport system. The ICG is not metabolized; it does not undergo
      enterohepatic recirculation. Thus, ICG excretion rate in bile reflects the
      hepatic excretory function and hepatic energy status. Because of these features,
      ICG has been found to be useful to assess liver function in liver donors and
      transplant recipients, in patients with chronic liver failure, and as a
      prognostic factor in critically ill patients. Further trials concerning liver
      dysfunction have applied the noninvasive bedside assessment of ICG among other
      clinical variables to monitor the progress and/or the reversal of liver
      dysfunction.

PMID- 16647476
TI  - Sedation in the critically ill patient.
AB  - Critically ill patients who require intensive care need effective analgesia and
      sedation to control potentially unpleasant symptoms, such as pain and anxiety.
      Analgesics and sedatives are also used to allow patients to tolerate nursing
      procedures and tracheal intubation as well as to aid mechanical ventilation.
      Metabolism of traditional opioids is dependent on organ function, which is
      abnormal among critically ill patients. The use of a score system to ensure
      sufficient but not excessive sedation should be mandatory. Sufentanil and
      remifentanil are more predictable opioids that are suitable for either sedation
      or analgesia in critically ill patients to achieve an adequate Ramsay score from
      2 to 4.

PMID- 16647477
TI  - Perioperative fluid management in kidney transplantation: is volume overload
      still mandatory for graft function?
AB  - Kidney transplantation is now recognized as the treatment of choice for patients
      with chronic renal failure. Despite the extension of indications to patients
      suffering severe hypertension, ischemic heart disease, and chronic heart failure,
      the worldwide results are superb. However, perioperative cardiac complications
      occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume
      expansion is still recommended to maximize graft functional recovery (up to 30
      mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent
      cardiac disease or poor myocardial function are exposed to the risk of fluid
      overload, acute respiratory failure, and prolonged ventilation. Among the last 90
      cases performed at our institution, good functional recovery of the graft was
      present in 94% of the patients within 2 weeks, despite a much more conservative
      intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7
      9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated
      only with donor age, while perioperative cardiovascular complications had been
      present in 9 cases (10%) who were coronary artery disease patients (55%). Age
      above 50 years was the only significant risk factor. Supranormal volume loading
      is probably not always warranted in kidney transplantation.

PMID- 16647478
TI  - Use of a blood gas analyzer to measure blood hemoglobin during liver
      transplantation: a study of 935 paired samples.

PMID- 16647479
TI  - Pathophysiology of bleeding in surgery.
AB  - Bleeding is a major surgical complication. Although mortality rates of 0.1% are
      observed for surgical procedures, it may be 5% to 8% for elective vascular
      surgery, and increase to 20% in the presence of severe bleeding. In major surgery
      for liver diseases, as well as in cardiac surgery, excessive blood loss is
      associated with increased mortality, morbidity, and intensive care stay.
      Approximately 75% to 90% of intraoperative and early postoperative bleeding is
      due to technical factors. However, in some cases either acquired or congenital
      coagulopathies may favor, if not directly cause, surgical hemorrhage.
      Uncontrolled bleeding leads to a combination of hemodilution, hypothermia,
      consumption of clotting factors, and acidosis, which in turn worsen the clotting
      process, further exacerbating the problem in a vicious bloody circle. At present,
      the standard treatment for surgical bleeding is the rapid control of the source
      of bleeding by either surgical or radiological techniques. Blood-derived products
      as well as hemostatic agents, such as aprotinin, tranexamic acid, and DDAVP, are
      widely used to improve hemostatic balance in bleeding patients. Recombinant
      activated factor VII (rFVIIa) has been reported to be effective for the treatment
      of surgical or traumatic massive bleeding unresponsive to conventional therapy.
      Although most reports are anecdotal, and therefore exposed to a "positive"
      selection bias, the number of cases is impressive, strongly suggesting that in
      such patients rFVIIa may afford a hemostatic advantage beyond that of
      conventional replacement therapy.

PMID- 16647480
TI  - Monitoring intraoperative coagulation.

PMID- 16647481
TI  - Recombinant factor VIIa in major abdominal surgery and liver transplantation.
AB  - The author reviewed the literature regarding recombinant activated Factor VII
      (rFVIIa) in major abdominal surgery and liver transplantation and concluded that,
      on the basis of evidence-based medicine, there is no evidence to support an
      extensive use of rFVIIa. Nevertheless, various case reports suggest the
      usefulness of rFVIIa to treat life-threatening bleeding after failure of
      conventional therapies. It appears that there is a consensus that rFVIIa can be
      used with good results as a rescue therapy in extremely severe situations.
      Economic cost and potential thrombosis risk remain arguments against more
      widespread use of rFVIIa. Doses from 5 to 120 kg/kg in each administration have
      been reported without clear evidence to support a specific protocol. Efficacy of
      15 to 20 kg/kg in surgical settings has been reported, but higher doses are more
      frequently used. The majority of the reviewed investigators accepted the use of
      rFVIIa after or simultaneously with the use of aprotinin; no data refute the
      safety of this association.

PMID- 16647482
TI  - Intraoperative coagulation evaluation of ischemia-reperfusion injury in small
      bowel transplantation: a way to explore.
AB  - BACKGROUND AND AIM OF STUDY: The success of intestinal transplantation is
      affected by the extreme susceptibility of the small bowel to ischemia-reperfusion
      (I/R) injury. Platelet aggregation decreases after reperfusion in small
      intestinal ischemia and liver transplantation. Thromboelastography (TEG) is a
      coagulation test performed whole on blood. The aims of this study were to assess
      coagulation derangements during bowel transplantation to define appropriate
      modalities of intraoperative coagulation monitoring. A secondary endpoint was to
      determine whether measurements of coagulation derangements were useful to
      estimate small intestinal I/R injury. MATERIALS AND METHODS: We recruited 19
      patients who had undergone elective small bowel transplantation for primary short
      gut syndrome. We divided our patients into two groups depending on their
      reperfusion injury as evaluated with a biopsy after reperfusion: group A composed
      of eight patients who had a reperfusion injury: group B composed of 11 patients
      who did not experience this problem. We measured five thromboelastogram
      indicators (r, k, angle, MA, CL30) at defined intervals: dissection phase (T1),
      vascular anastomoses phase (T2) as well as 30 minutes (T3) and 120 minutes (T4)
      after reperfusion during the intestinal reconstruction phase. RESULTS: We did not
      observe any significant difference between intraoperative blood loss, core
      temperature, or volume of fluid fresh frozen plasma, or platelet administration.
      Angle and MA were decreased significantly among patients with reperfusion injury.
      DISCUSSION: Patients showed a hypocoagulation pattern during all the
      manipulations. This derangement did not depend on the ischemia time. In patients
      with I/R injury the angle and MA did not change during ischemia, but did change
      significantly upon reperfusion. Several mechanisms may cause coagulation
      derangements. During the ischemic period, there may be damage to the vascular bed
      of the ischemic organ. When arterial blood passes through the damaged vascular
      bed after reperfusion, platelet activation occurs to varying degrees, resulting
      in reduced platelet function. CONCLUSION: Further studies are needed to confirm
      this preliminary work, which was limited by the low number of patients, in order
      to elucidate relevant mechanisms and develop predictive algorithms.

PMID- 16647483
TI  - Intraoperative coagulation monitoring and small bowel transplantation: a way to
      explore.
AB  - BACKGROUND: The existence of coagulation disorders during intestinal
      transplantation is getting more important for a correct anesthetic management.
      Both a condition of hypocoagulation and hypercoagulation can happen during the
      intraoperative course. Thromboelastography (TEG), a test on whole blood
      coagulation, allows measurement of different phases of coagulation function. The
      aims of our study were to evaluate coagulation derangements during bowel
      transplantation using TEG. MATERIALS AND METHODS: We measured cold ischemia time
      in 19 patients who underwent general anesthesia for intestinal transplantation.
      We measured five TEG indicators (R, K, angle, MA, CL50) at defined intervals:
      dissection phase (T1), vascular anastomosis phase (T2), 30' (T3) and 120' (T4)
      after reperfusion during the intestinal reconstruction. RESULTS: We found a
      statistically significant difference between MA measured at T1 versus T3 and T4.
      There was no significant relation between MA derangements and ischemia time.
      CONCLUSIONS: Patients showed hypocoagulation pattern during all periods. MA
      indicator variation between the initial value and the value after reperfusion may
      relate to release of hypocoagulation factors. We observed important coagulation
      derangements during small bowel transplantation, particularly on platelet
      function after graft reperfusion. The derangements did not depend on ischemia
      time.

PMID- 16647484
TI  - Pathophysiology of ischemia-reperfusion injury.
AB  - Our studies characterized the intestinal microcirculatory changes in canine
      models of intestinal hypoperfusion (hemorrhagic shock) or ischemia-reperfusion
      (small bowel autotransplantation). The villus microcirculatory parameters
      (functional capillary density, mean red blood cell velocity) were observed by
      intravital microscopy using orthogonal polarization spectral imaging. The
      leukocyte reaction (rolling and firm adherence) in the mesentery was quantified
      by using conventional fluorescence videomicroscopy. The investigations were aimed
      at determining whether the compromised intestinal villus perfusion could be
      influenced by endothelin-A receptor inhibition, volume resuscitation, or ischemic
      preconditioning. The results demonstrated the pathophysiological significance of
      endothelin-A receptor activation in ischemia-reperfusion-induced microcirculatory
      changes. Second, it was shown that colloid fluid therapy with hydroxyethyl-starch
      effectively ameliorated the microcirculatory consequences of hypovolemia, which
      correlated with a lower endothelin release. Third, ischemic preconditioning when
      applied 60 minutes before ischemia, inhibited the reperfusion-induced superoxide
      production, improved capillary perfusion, and attenuated leukocyte activation
      within the intestinal graft. Among the examined therapeutic strategies aimed at
      improving the outcome of intestinal microcirculatory dysfunction, endothelin-A
      receptor antagonist pretreatment and ischemic preconditioning are promising tools
      to decrease the harmful consequences of ischemia/reperfusion.

PMID- 16647485
TI  - Pediatric liver transplantation: preliminary results at IsmeTT-Palermo.

PMID- 16647486
TI  - Pathophysiology of abdominal compartment syndrome.
AB  - For over a century, raised intra-abdominal compartment syndrome (ACS) has been
      known. The physiology and clinical results of this syndrome produce significant
      morbidity and quite high mortality rates. Increased intra-abdominal pressure
      causes progressive hypoperfusion and ischemia of the intestines as well as other
      peritoneal and retroperitoneal structures, including the pulmonary,
      cardiovascular, renal, splanchnic, and central nervous systems. The most
      effective prevention of ACS is early recognition and preemptive interventions, as
      well the choice of appropriate abdominal closures with constant care and
      surveillance in intensive care units.

PMID- 16647487
TI  - Intra-abdominal hypertension in nonelective surgery: a preliminary report.
AB  - Intra-abdominal hypertension (IAH) is recognized to be associated with adverse
      outcomes in critically ill patients. Etiologic factors for IAH can be divided
      into three categories: medical, posttraumatic, and surgical/postoperative. No
      studies have been performed on patients who underwent nonelective surgery, so our
      aim was to determine prospectively the incidence of IAH among these patients
      during their intensive care stay to correlate intra-abdominal pressure (IAP) and
      other parameters. Abdominal pressure was recorded twice daily with the standard
      method. The study group enrolled 22 patients who underwent an abdominal operation
      that met urgency criteria and with a postoperative intensive care unit (ICU) stay
      of at least 48 hours. Several serum and clinical parameters were studied for the
      first 5 postoperative days as well as during ICU and hospital stay as well as
      monitored hospital mortality. Our results demonstrated that mortality was
      definitely higher among patients who developed IAH compared with non-IAH
      patients. Our results highlighted that a strong correlation existed between
      increasing values of IAP and worsening serum creatinine and PaO2/FiO2 quotient
      among patients who underwent nonelective surgery.

PMID- 16647488
TI  - Abdominal hypertension and liver dysfunction in intensive care unit patients: an
      "on-off" phenomenon?
AB  - Intra-abdominal hypertension (IAH) can affect liver hemodynamics but it is not
      known if has a significant clinical impact on liver function. The aim of this
      study was to investigate the relationship between IAH and liver function. A
      prospective study was performed in 110 adult intensive care unit (ICU) patients.
      Intra-abdominal pressure (IAP) was measured on admission and every other day, and
      liver sequential organ failure assessment (SOFA) score was collected whenever IAP
      was measured. IAH was defined by a IAP >or= 10 mm Hg, and liver dysfunction was
      defined by a hepatic SOFA score >or= 2. An overall IAH incidence of 56.3% was
      found (n = 62). Thirty-three patients presented a liver SOFA score >or= 2, with
      an overall incidence of 30%. Liver SOFA score of the group of patients with
      abdominal hypertension was higher than in group of patients without abdominal
      hypertension. (0.8 +/- 1.05 vs 0.4 +/- 0.7; P < .05), but IAH and liver
      dysfunction were not significantly associated (chi2 = 2.03; P = .15). When the
      whole sample was divided according to the worst IAP score (IAP < 10, IAP between
      10 and 15, and IAP > 15), the corresponding liver dysfunction scores in the three
      groups were 0.35 +/- 0.6, 0.74 +/- 1, and 1.2 +/- 1.3, respectively (P = .01). A
      strict association between IAH and liver dysfunction was not found. Most likely,
      low levels of IAH, although able to reduce liver blood flow, are not per se
      sufficient to produce a real dysfunction; however, a correlation between the
      degree of IAH and the degree of hyperbilirubinemia exists. IAH does not seem to
      be an "on-off" phenomenon, but produces liver alterations for increasing levels
      of its severity.

PMID- 16647489
TI  - Postoperative sedation and analgesia after pediatric liver transplantation.
AB  - The goal of sedation in the pediatric intensive care unit (PICU) is to produce a
      calm and comfortable child, free from pain and discomfort. Children receiving
      liver transplantation need analgesics to control pain from surgical incisions,
      drains, vascular access, or endotracheal suctioning. Sedatives are used to
      facilitate the delivery of nursing care, to prevent self-extubation, and to
      facilitate mechanical ventilation. Optimal sedation produces a state in which the
      patient is somnolent, responsive to the environment but untroubled by it, and
      with no excessive movements. A common problem in the PICU is the fluctuation in
      the delivery of sedatives and analgesics depending on the health care providers
      and on a breakdown in communication between physicians and nurses to define end
      points for pharmacological therapy. This variability more often leads to
      oversedation rather than undersedation. Oversedation delays extubation, promotes
      ventilator-associated pneumonia, and increases the risk of reintubation. The use
      of written sedation policies to guide practice at the bedside reduces the length
      of time for which patients require mechanical ventilation and the length of PICU
      stay. Protocols for drug administration practices increase patient safety during
      mechanical ventilation, promote nursing autonomy, and facilitate communication
      between nurses and physicians as well as between nurses.

PMID- 16647491
TI  - Attitudes of primary care professionals in Spain toward xenotransplantation.
AB  - OBJECTIVE: The deficit in transplantable organs is making it necessary to find
      alternative sources. One possibility is xenotransplantation. However, the use of
      animal organs may be rejected by society and among health professionals. Primary
      Care is fundamental for promoting matters of health; in Spain it has access to
      nearly 100% of the population. Our objective was to analyze the acceptance of
      this therapy, although it is experimental, among Primary Care professionals,
      given that they are the ones most involved in spreading information about this
      therapy if it was confirmed to be useful. MATERIALS AND METHODS: A random sample
      was stratified by sex, job category, and geographical location among Primary Care
      personnel, including 428 professionals in 32 health centers among population of
      2851 professionals. Attitudes toward xenotransplantation were evaluated using a
      questionnaire on psychosocial attitudes validated in our geographical area.
      Contact was made in each center with the Doctor Coordinator for doctors, the
      Nursing Coordinator for nurses, and an Administrative Officer for ancillary
      personnel. The chi-square test and Student t test were applied to evaluate
      categorical and continuous data, respectively. RESULTS: Attitudes toward
      xenotransplantation were similar to those obtained in human organs: favorable in
      79% (n = 325), whereas 19% (n = 78) had doubts and 2% (n = 10) were against. The
      attitude was more favorable in men (89% vs 72%; P < .000), those who had cared
      for transplant patients (84% vs 71%; P = .009), those with previous experience in
      organ donation and transplantation (84% vs 75%; P = .033), those with an attitude
      in favor of cadaveric organ donation (83% vs 66%; P < .0001), and those in favor
      of living donation of the kidney (P < .000) or the liver (P < .000), as well as
      those who believed that they may need a transplant at some time in the future
      (84% vs 74%; P = .045). There was a clear difference in attitude according to job
      category (P = .018): approval rates were 89% for doctors, 76% for nurses, and 70%
      for ancillary personnel. CONCLUSIONS: Attitudes toward future application of
      xenotransplantation were quite positive among doctors. However, the attitudes of
      nursing and ancillary personnel were similar to those of the general population.
      The main factors related to such an attitude depended mainly on the previous
      relationship and attitude of the respondent toward human organ donation and
      transplantation.

PMID- 16647492
TI  - Ancillary hospital personnel faced with organ donation and transplantation.
AB  - OBJECTIVE: To reduce the number of family organ donation refusals, it is
      necessary not only to act on the general public but also on the health care
      system. In this respect, there are data suggesting that the percentage of
      hospital personnel against donation is high, especially among ancillary
      personnel. The objective herein was to analyze the attitudes of ancillary
      hospital professionals toward donation of their own organs and determine factors
      that conditioned such attitudes. MATERIALS AND METHODS: A random sample in a
      third-level hospital with a solid organ transplant program was stratified by
      ancillary services: administrative, porters, maintenance, cleaning, and cooking.
      Attitudes toward donation of one's own organs after death were evaluated using a
      questionnaire on psychosocial aspects validated in our area. It included various
      psychosocial variables that could affect such attitudes. The Student t test and
      chi-square test were used to evaluate the data. RESULTS: We analyzed 277
      respondents of mean age 43 +/- 8 years and 96% women. The level of acceptance of
      organ donation was 64% (n = 178), whereas 46% were either against or undecided (n
      = 98). The variables which determined the attitudes were understanding of brain
      death (P = .004); attitude toward cadaveric manipulation, especially toward
      autopsy (P = .013) and cremation (P = .004); concern about mutilation after
      donation (P = .014); religion (P = .032); partner's attitude toward donation (P <
      .0001); and possibility of needing an organ in the future (P = .031).
      CONCLUSIONS: Ancillary hospital personnel had similar attitudes toward donation
      as those of the general public as observed in other studies. The attitudes were
      determined by many psychosocial factors. A campaign to raise awareness among
      professionals has become a priority, given that working in a hospital, their
      unfavorable attitude could have a strong negative impact on the general public.

PMID- 16647493
TI  - Primary care doctors faced with living organ donation.
AB  - OBJECTIVE: The attitudes of health care personnel, specifically doctors, have a
      significant influence on public attitudes toward organ donation and
      transplantation. The objective herein was to analyze the attitudes of Primary
      Care (PC) doctors toward living organ donation and to determine the psychosocial
      factors that condition these attitudes. MATERIALS AND METHODS: A random sample
      was stratified by geographical location (six health areas in our community) among
      PC doctors, including 155 respondents from 32 health centers. Attitudes toward
      donation were evaluated using a psychosocial questionnaire validated in our
      geographical area. Contact was made with the Doctor Coordinator in each center
      for distribution of the questionnaires, which were completed anonymously. The chi
      square test and Student t test were applied to evaluate the data. RESULTS: When
      the living donor is not related, only 21% (n = 32) of PC doctors were in favor of
      living kidney donation, and only 20% (n = 31) for living liver donation (P >
      .05). In contrast, these percentages were 90% and 89% in favor of kidney and
      liver related donation, respectively. Upon analysis of the psychosocial variables
      affecting these attitudes, there was only an association with their partner's
      opinion (P = .009 for kidney and P = .000 for liver), and the possibility of
      needing a transplant oneself (P = .000). CONCLUSIONS: PC doctors have favorable
      attitudes toward related living donation. If living donation is promoted by
      transplant coordination units, such PC professionals could act as a source of
      positive information about the matter for the general public.

PMID- 16647494
TI  - Attitudes toward organ donation in rural areas of southeastern Spain.
AB  - OBJECTIVE: Rural areas present a worse attitude toward organ donation. However,
      the factors conditioning this attitude are not well known. Our aim was to
      determine the profile of the population opposed to donation in rural areas.
      MATERIALS AND METHODS: A random sample stratified by age and sex was obtained
      from municipalities with less than 10,000 inhabitants. Attitudes toward donation
      were assessed by a questionnaire which evaluated variables that may influence
      these attitudes. A descriptive statistical study used the Student t test and chi
      square test as well as a logistic regression analysis. RESULTS: Among 181
      respondents, 63% were in favor of donation and 37% against or undecided. Among
      the reasons to be against donation were rejection of body mutilation (43%) and
      fear of apparent death (41%). The psychosocial variables against donation were
      age >or=44 years, primary education or below, no previous experience with
      donation, no prosocial activities, an unfavorable opinion of the partner, and
      fear of corpse mutilation. The variables persisting in the multivariate analysis
      were level of education, previous experience, prosocial activities, and fear of
      corpse manipulation. CONCLUSIONS: Among the rural population the profile of a
      person opposed to donation was someone older than 44 years, with a low level of
      education and no previous experience with donation, who does not participate in
      prosocial activities and is opposed to corpse manipulation.

PMID- 16647495
TI  - Attitudes of resident doctors toward different types of organ donation in a
      Spanish transplant hospital.
AB  - OBJECTIVE: Our aim was to analyze acceptance of cadaveric and living organ
      donation for transplantation among resident doctors, given that they are the new
      professionals of medicine who will have to encourage and develop transplant
      programs. MATERIALS AND METHODS: A random survey was performed on resident
      doctors in a third-level hospital with an organ transplant program which is
      accredited for undergraduate and postgraduate education (n = 171). Attitudes
      toward cadaveric and living donation were evaluated using a questionnaire
      including various psychosocial variables that might affect such attitudes. We
      used the Student t test and the chi-square test. RESULTS: The sample was composed
      of responses by 171 resident doctors of mean age 28 +/- 4 years with 56% women.
      Attitudes toward cadaveric donation were favorable in 92% (n = 157). As for
      living donation, the percentage in favor of nonrelated donation was low: 23% for
      kidney and 19% for liver. However, when the donation was from a relative, the
      percentages increased to levels similar to those of cadaveric donation, namely
      88% and 85% for kidney and liver, respectively. No differences were observed in
      attitudes toward cadaveric or living donation according to various psychosocial
      variables. CONCLUSIONS: The trainee doctors showed favorable attitudes toward
      human cadaveric organ donation as well as living related donation, which suggests
      a relaunch of living donors in the near future. However, there was not much
      acceptance of nonrelated donation, as has also been seen in studies of the
      general public in our geographical area.

PMID- 16647496
TI  - Postoperative outcome of open donor nephrectomy under epidural analgesia: a
      descriptive analysis.
AB  - PURPOSE: Patients subjected to open donor nephrectomy with epidural analgesia
      were analyzed to determine whether there was a relation between catheter
      placement site and the appearance of complications and satisfactory analgesia and
      to determine whether this factor had an impact upon recovery and return to
      preoperative life. METHODS: A cohort of 36 open donor nephrectomies were
      performed with postoperative epidural analgesia. Two groups were analyzed:
      thoracic (22 patients) and lumbar catheters (14 patients). There was a 72-hour
      evaluation followed by phone contact. Besides detecting related complications
      pain was evaluated using a visual analog scale (VAS 0 to 10) in the
      postanesthesia care unit and at 6, 24, 48 and 72 hours postoperatively.
      Satisfactory analgesia was defined as a VAS of 3 or less. RESULTS: In all cases
      the analgesic solution was composed of bupivacaine 0.125% with an opioid in 97%.
      Patients showed complications in 72% (26/36); the only significant association
      was motor blockade in the lumbar group (21% vs 0% in the thoracic, P = .023).
      Patients had a mean VAS of 2.83 +/- 1.77. There was a larger proportion of pain
      free patients (VAS 0) in the thoracic group; in addition, there was no VAS of 10
      in this group. Ambulation was resumed in less than 24 hours in 57% of patients,
      having a mean VAS of 2.1 +/- 1.5 compared with 3.2 +/- 1.6 among those who
      ambulated after 24 hours (P = .04). There was no association between
      perioperative pain control and the interval to normal activities. CONCLUSIONS:
      Without a control group, we can hardly evaluate the impact of epidural analgesia
      on perioperative outcome. Notwithstanding, the obtained pain control may justify
      its use in these patients. An important issue is to maintain a low VAS (<3),
      especially in the first 24 hours, which may make a clinically important
      difference for early ambulation.

PMID- 16647497
TI  - The perfusion pressure in non-heart-beating donors may expand the glomeruli.
AB  - INTRODUCTION: We have observed expanded glomeruli in biopsies of kidneys from non
      heart-beating donors (NHBDs). We sought to determine the differences in
      glomerular size between NHBDs and brain-dead donors and to assess whether
      glomerular size impacted graft outcome. METHODS: We estimated the glomerular area
      using the maximal planar area (MPA) method in 198 pretransplant biopsies from 119
      donors: 54 (45.4%) NHBDs and 65 (54.6%) brain-dead donors. Donor data and graft
      outcomes were correlated with MPA and percentage of glomerulosclerosis. The range
      of follow-up was 1 to 3 years. Uni- and multivariate analyses were performed.
      RESULTS: MPA was larger among NHBDs. MPA and GS both significantly correlated
      with donor age. The association between MPA and age was independent of nephron
      loss (ie; GS). Increased glomerular size was only observed among donors younger
      than 50 years. Graft survival and function were not independently associated with
      MPA. Donor age was a better predictor of graft outcome. CONCLUSIONS: The
      perfusion pressure used in NHBDs may expand the glomeruli, but this maneuver does
      not have any effect on graft outcome. Among donors without severe changes,
      glomerular size increment shows a limit around the sixth decade of life. In our
      study, MPA was not an independent predictor of graft survival or function.

PMID- 16647498
TI  - Detection of amastigotes of Trypanosoma cruzi in a kidney graft with acute
      dysfunction.
AB  - We described a case of allograft kidney dysfunction associated with renal
      parenchymal infection with amastigotes of Trypanosoma cruzi. The patient was
      diagnosed as being chronically infected prior to transplantation. The infection
      was probably acquired by blood transfusion. He could not complete antiparasitic
      treatment due to drug toxicity. He was transplanted from a cadaver who showed a
      negative test for Chagas' disease. One year after transplantation the serum
      creatinine progressively increased. Histological examination of renal biopsy
      revealed intracytoplasmic amastigotes of T cruzi. No evidence of other specific
      alterations in the graft was detected. It was unknown whether graft dysfunction
      was only due to parasitic infection. The present case confirmed that T cruzi can
      infect kidney grafts and that immunosuppression in kidney transplantation is
      potentially a cause of dissemination of Chagas' disease.

PMID- 16647499
TI  - Effect of obese living donors on the outcome and metabolic features in recipients
      of kidney transplantation.
AB  - Living kidney donors must be evaluated carefully focusing on risk factors for
      long-term complications. Our transplant center performs 70% of its kidney
      transplantations from living sources including 19.9% obese donors. We evaluated
      the long-term follow-up of recipients of organs from 37 living donor patients
      with obesity defined by a body mass index (BMI) > 30 kg/m2. We compared this
      group with a control group of normal BMI before donation. The follow-up was 50.8
      +/- 28.5 months. We observed a lower glomerular filtration rate among organs from
      obese versus non-obese donors. At the same time we reviewed percentage of acute
      rejection episodes (ARE), primary allograft function, and surgical complications
      we observed incidence of ARE higher among the group who received kidneys from
      obese donors.

PMID- 16647500
TI  - Kidney transplantation with grafts from non-heart-beating donors.
AB  - We analyzed the function and outcome of 16 kidney transplants performed in our
      hospital from non-heart-beating donors who were harvested at other hospitals. The
      cold ischemia times were longer and the delayed graft function rates higher.
      However, graft function was no different from that of kidneys from heart-beating
      donors. This experience has encouraged us to use this type of donor to reduce the
      transplant waiting list.

PMID- 16647501
TI  - The fate of organs refused locally and transplanted elsewhere.
AB  - The number of kidney allografts procured from deceased donors has been fairly
      constant in the past few years, while organs from living donors steadily
      increase. In our program, existing protocols refused some kidneys which were
      subsequently accepted and transplanted at other hospitals. Thus, a review of our
      criteria to accept kidneys became necessary. METHODS: We studied the outcome of
      all kidneys refused by us but transplanted in other programs between 2002 and
      2004. The data analyzed included ID no. donor, transplant center, procurement
      date, donor age, ischemic times, recipient alive or dead, creatinine level (when
      it was offered), initial function, hypertension, diabetes mellitus, biopsy,
      reason why the kidney was not accepted in our program, kidney functioning or
      lost, and cause of graft failure. The chi-square, Fisher, and t tests were used
      to analyze our data; P values of <.05 were regarded as significant. RESULTS:
      Originally 137, we excluded kidneys exported due to mandatory sharing (26 of 137
      = 18.97%) and multiorgan placement (10 of 137 = 7.3%). Thus, 101 kidneys were not
      accepted by us because they did not meet the existing criteria of our program,
      but were accepted elsewhere. Reasons for nonacceptance were divided into donor
      quality, donor social history, donor age, donor size/weight, positive serological
      test, as well as organ preservation time, organ anatomical damage, elevated
      creatinine, abnormal urinalysis, abnormal biopsy, and decreased urine output.
      Donor issues were 66 of 101 (65.3%) with a graft loss of 13.6%, and organ issues
      were 35 of 101 (34.7%) with a graft loss of 66.6%. Donor quality totaled 24 of 66
      (36.4%) and donor social history totaled 20 of 66 (30.3%); these were the most
      common causes for kidney nonacceptance related to donor issues. Reasons related
      to organ quality included elevated creatinine (15 of 35 = 42.9%; graft loss,
      46.6%), and abnormal biopsy (9 of 35 = 25.7%; graft loss, 11.1%) and organ
      anatomical damage (4 of 35 = 11.4%; graft loss, 75%) (P = .42). Graft loss was
      more frequent with creatinine levels above 2.4 mg/dL (P < .001, RR gf = 1.5).
      Long-term fate of these 101 kidneys transplanted elsewhere: 82 (81.2%) were still
      working while 19 (18.8%) were lost. The causes of graft loss were renal artery
      thrombosis (42.1%), renal venous thrombosis (26.3%), death for other reasons
      (15.8%), graft never worked (10.5%), and ESRD (5.7%). The results suggest that
      the criteria for refusal related to donor issues, including hypertension,
      diabetes mellitus, donor age and donor size, should be revised owing to the low
      percentage of graft loss. Other donor issues such as positive serological test
      and donor social history (drug use, alcoholism) represent a serious potential
      risk for the health of recipients; for this reason, considering these persons as
      possible donors is very difficult irrespective of the graft outcome. Kidney
      refusals related to organ issues (especially elevated creatinine and anatomical
      damage) due to the very high percentage of graft loss should be considered high
      risk and probably be excluded. The increase in the demand of kidneys to be
      transplanted is a very important reason for a continuous and systematic review of
      donor exclusion criteria in every transplant program. The results presented here
      have helped us to improve both our outcomes and utilizations based on scientific
      evidence.

PMID- 16647502
TI  - Renal transplantation in diabetic patients.
AB  - OBJECTIVE: Diabetes is one of the main causes of end-stage renal disease (ESRD)
      and admission to hemodialysis, and the demand for kidney transplantation in this
      population has increased. Our aim was to evaluate the clinical aspects and
      survival of diabetic patients with kidney transplants by comparing them with the
      nondiabetic population. MATERIALS AND METHODS: Patients transplanted during the
      period from 1994 to 2003 were evaluated for this study. The transplant and
      demographic characteristics were analyzed by the chi-square test and Student t
      test according to the type of variable. Kaplan-Meier curves and the log-rank test
      were used to evaluate the graft and patient survival. RESULTS: From a total of
      523 consecutive renal transplants, 35 (6.6%) were diabetics who were older than
      nondiabetics (47 +/- 11 years vs 37 +/- 16, P < .002). Patients received
      immunosuppression with cyclosporine (84.3%), tacrolimus (11.2%), azathioprine
      (46.6%), mycophenolate mofetil (43.5%), and steroids (all patients). The diabetic
      patients had a higher percentage of living donors (33.5% vs 17.2%; P = .04).
      Graft survival rates at 1, 3, and 5 years were 82.7%, 70.9%, and 63.0% in the
      diabetic patients and 87.6%, 79.0%, and 72.5% (P = .6) in the nondiabetic
      patients. Patient survival at 5 years was 90.5% in diabetic patients vs 89.0% in
      nondiabetic patients (P = .9). CONCLUSIONS: No differences were found in our
      series in transplant complications or survival in the diabetic patients compared
      with the nondiabetic patients. Kidney transplants, even with living donors, must
      be offered to well-selected diabetic patients without reservations.

PMID- 16647503
TI  - Prevalence of HLA antibodies and its impact on graft function in a group of
      kidney transplant recipients: a cross-sectional study.
AB  - HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft
      survival. The current study was designed to document the prevalence of HLA Abs in
      a group of kidney transplant recipients (KTR) and its impact on graft function.
      PATIENTS AND METHODS: 283 KTR transplanted between January 1990 and December 2003
      who had a functional graft were invited to participate. 198 KTR were enrolled.
      HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was
      assessed by DeltaCr and GFR calculated by the Levey formula. RESULTS: Median post
      kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four
      (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class
      I and II Abs, ten were positive only for class I, and 23 for class II. Overall,
      no significant difference was seen in renal function. The DeltaCr for Ab positive
      and Ab negative were -0.24+/-0.84 and -0.17+/-0.60 mg/dL (P=0.54), respectively.
      The GFR for Ab positive and Ab negative were 64.4+/-26 and 60.2+/-20 mL/min
      (P=0.25), respectively. No statistically significant difference was found between
      HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT
      pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy.
      Adjusting analysis by transplant year showed no significant difference.
      CONCLUSION: The prevalence of HLA antibodies was similar to previous reports. In
      this cross-sectional study, the presence of HLA antibodies was not related to a
      negative impact on renal function.

PMID- 16647504
TI  - Comparison between clinical and histopathological scoring in cadaveric kidney
      transplantation and its correlation with posttransplant evolution.
AB  - INTRODUCTION: There are several scoring systems, both clinical (Deceased Donor
      Score [DDS]) and histopathological (Remuzzi [REM]), that attempt to determine
      acceptability criteria for deceased donor kidney transplant. A retrospective
      study was performed among a group of kidney transplant recipients to evaluate
      posttransplant evolution with clinical and histopathological scores. MATERIALS
      AND METHODS: Among 107 first deceased donor kidney transplant patients, 95 had
      undergone a pretransplant biopsy. Donor age was 38.46 +/- 16.9 years; recipient
      age: 49.2 +/- 16.3 years; DDS was 15.58 +/- 7.29. REM was 2.89 +/- 1.7. Delayed
      graft function was 64.2%. Induction therapy was administered to 49.5%. Cold
      ischemia time (CIT) was 1364 +/- 348 minute. Time on dialysis was 2275 +/- 1501
      days. Induction therapy, immunosuppressive regimens, CIT, and time on dialysis
      were not significantly different among the groups. One-year patient and graft
      survival were 94.5% and 86%, respectively and 2-year values, 92.6% and 81%,
      respectively. CONCLUSION: DDS showed a significant correlation with serum
      creatinine values over 1 and 2 years. REM did not show a significant association
      with any events. The differences were sustained after adjusting for other
      variables. Graft survival maintained a strong correlation with DDS categories and
      no association with REM. The clinical characteristics of a deceased donor
      appeared to be of greater importance than the biopsy findings in terms of
      posttransplant events.

PMID- 16647505
TI  - Use of enteric-coated mycophenolate sodium in de novo renal transplant recipients
      with high incidence of delayed graft function.
AB  - Patients with delayed graft function (DGF) are at risk of increased incidence for
      acute rejection episodes (ARE). Mycophenolate mofetil or induction therapy has
      produced a reduction in ARE incidence. An open, prospective, 3-month trial was
      performed in a group of Argentinian renal transplant recipients. We recruited 46
      patients, 71.7% men, aged 41.7 +/- 13.8 years; including 36 (78.3%) recipients of
      cadaveric donors (CD) who were aged 43.4 +/- 15.5 years with a cold ischemia time
      of 19.4 hours +/- 5.4 minutes, and 10 (27.7%) recipients of living donors (LD)
      aged 37.8 +/- 12.9 years. HLA mismatches >or= 3 were observed in 58.4% of CD and
      in 7% of LD. All patients received two doses of basiliximab (20 mg each, days 0
      and 4), cyclosporine microemulsion (CsA-ME) monitored by the second-hour
      concentrations (C2), enteric-coated mycophenolate sodium (EC-MPS; 720 mg twice a
      day, and steroids. A 58% incidence of DGF was observed. At the end of the third
      month the incidence of biopsy-proven ARE was 15%, with a median serum creatinine
      of was 1.54 +/- 0.42 mg/dL, including three grafts lost. Two patients died. No
      patient required EC-MPS dose discontinuation but 20% of patients required dose
      adjustments. The absence of discontinuations and the low incidence of dose
      adjustments of EC-MPS in this high-risk de novo population provided support of a
      suitable tolerability profile for this EC-MPS, and the possibility to impact
      efficacy results.

PMID- 16647506
TI  - Basiliximab: a comparative study between the use of the recommended two doses
      versus a single dose in living donor kidney transplantation.
AB  - Basiliximab (Simulect) is a high-affinity chimeric and humanized monoclonal
      antibody, directed against the alpha chain of human interleukin-2 receptor
      (CD25). The administration of two doses (20 mg intravenously per dose), one given
      2 hours before transplantation and the second on day 4 posttransplant, provides
      suppression of the interleukin-2 receptor for up to 45 days, reducing the rate of
      acute rejection in kidney transplantation. This study was designed to compare the
      efficacy of a single dose of Simulect to the recommended two doses. The other
      objective was the reduction of the costs related to the standard two dose
      protocol. Fifty-two patients were included: group I (32 patients) received two
      doses of Simulect; group II (20 patients) received one dose. There were 39 living
      related donors and 13 living unrelated. All patients were followed for 1 year.
      Maintenance immunosuppression consisted of tacrolimus or cyclosporine,
      mycophenolate mofetil, and steroids. The diagnosis of rejection was made
      clinically. All episodes were treated with intravenous steroids. The incidence of
      rejection was similar in both groups; there was no graft loss to rejection. There
      were two deaths in group I, and one death in group II, yielding graft and patient
      actual survival rates at 1 year of 93% and 95%, respectively. These results
      suggest that Simulect is equally effective when administered in two doses or in a
      single dose in kidney transplantation. The reduction of cost by giving a single
      dose is significant, especially in developing countries without national health
      insurance.

PMID- 16647507
TI  - Study of factors that affect complications after renal transplantation.
AB  - There are no multifactorial studies of complications after renal transplant in
      the Hispanic population. The objective of this study was to identify which
      factors are associated with the development of complications after renal
      transplantation. This retrospective study was performed on all patients
      transplanted in the Puerto Rico Transplant Program during 2002. Independent
      variables included preoperative albumin, white blood cell (WBC) count,
      hemoglobin, creatinine, weight, height, body mass index (BMI), type of dialysis,
      time on dialysis, and urine production after transplant. Dependent parameters
      included posttransplant diuresis, wound infection, wound dehiscence, lymphoceles,
      acute tubular necrosis, length of stay, postoperative weight, graft survival, and
      patient survival. Data were analyzed with parametric and nonparametric techniques
      using STAT 200 software. Sixty-four patients were included in the study: 37 male,
      27 female. No significant differences in complication rate or length of stay were
      found with age, preoperative albumin, WBC count, hemoglobin, creatinine, weight,
      height, dialysis modality, and donor type. Significant factors included type of
      dialysis, time on dialysis, and BMI. Preoperative albumin if > 3 was not a
      prognostic indicator for the development of surgical complications following
      renal transplantation. Only preoperative weight, BMI, and dialysis duration were
      significant factors in the development of postoperative complications and
      prolonged hospital stay in this sample Hispanic transplant population. These data
      are important in formulating selection, education, and transplant management
      policy.

PMID- 16647508
TI  - HLA is not predictive of posttransplant diabetes mellitus.
AB  - AIMS: New-onset posttransplant diabetes mellitus (PTDM) is a frequent
      complication of kidney transplantation. The goal of this study was to identify if
      the tendency to develop PTDM was associated to the HLA, as is seen in the general
      population. METHODS: A retrospective study was made of 525 patients who underwent
      renal transplantation between 1997 and 2004. They were divided into three
      categories depending on the diabetic status before and after kidney
      transplantation. The HLA profile of each patient was identified for class 1 and
      class 2 antigens including HLA-A, HLA-B, and DR-R. Antigen frequencies were
      calculated and gene frequencies derived. These were compared among the three
      groups and with the published data for the Puerto Rico population. Other
      variables studied included weight, age, gender, and family history. RESULTS:
      Seventy-two of 526 (13.7%) were diabetic before transplantation; 92/453 (20.3%)
      developed PTDM after kidney transplantation. Pretransplant diabetics showed a
      higher incidence of A3 (0.1102 vs 0.0869 vs 0.0361), DR4 (0.3334 vs 0.1932 vs
      0.2124), and DR-13 (0.1835 vs 0.1115 vs 0.1175) than nondiabetics and the normal
      Puerto Rican population. Posttransplant diabetics showed a higher A3 (0.1154) and
      a higher DR3 (0.0675 vs 0.0295 vs 0.0022) than nondiabetics and normal
      population. CONCLUSION: PTDM was not associated statistically with the HLA in
      this group of transplant recipients, although A3 and DR3 were higher. Patients
      with the phenotype that is related to diabetes in the normal population did not
      have a higher incidence of diabetes in this series.

PMID- 16647509
TI  - Prevalence of erectile dysfunction in kidney transplant recipients.
AB  - Prevalence and severity of erectile dysfunction increase with advancing age.
      Patients with end-stage renal disease (ESRD) experience disturbances in erectile
      function related to organic factors including as uremia, hypertension, endocrine,
      and nonorganic factors like depression. Recipients of kidney transplants show a
      high prevalence of erectile dysfunction, 32.2% to 50.7%. We conducted a study of
      the prevalence of erectile dysfunction among male renal transplant recipients
      using the International Index of Erectile Function. Among 182 men with kidney
      transplantations, there were 89 recipients (48.9%) with erectile dysfunction; 60
      recipients had normal sexual function (32.9%); and whereas 33 recipients had no
      sexual activity.

PMID- 16647510
TI  - Assessing the risk of infection and rejection in Hispanic renal transplant
      recipients by means of an adenosine triphosphate release assay.
AB  - INTRODUCTION: Because of the necessary immunosuppression, transplant recipients
      have a high risk of infection. Conversely, underimmunosuppression carries with it
      the risk of rejection. It would be quite useful to have a test that could
      differentiate between infection and rejection in renal transplant patients and
      better still, to predict which patients are at risk of complications. A new
      assay, which measures adenosine triphosphate (ATP) synthesis by CD4+ T cells in
      response to stimulation by phytohemagglutinine (Immuknow assay, Cylex, Inc) is
      undergoing clinical evaluations. Preliminary investigations suggest that this
      test could be useful to assess and predict the immune status of patients with
      other conditions. METHODS: We examined the records of all patients who received a
      kidney transplant in our program between August 2004 and January 2005. Of 64
      patients, 58 had pretransplant and posttransplant ATP level determinations. We
      searched for associations between ATP levels and immunosuppression type, doses,
      and levels; creatinine levels; white blood cell count; tissue typing; preformed
      antibodies; as well as ATP levels on infection and rejection, and changes in ATP
      levels with time. Chi-square, Fisher, t test, analysis of variance (ANOVA), and
      relative risks were used for analysis of data. RESULTS: There was no relation
      between ATP levels and immunosuppression type, doses, or levels; creatinine
      levels; white blood cell counts; HLA; and panel-reactive antibody (P > 0.05).
      However, patients with moderate or high pretransplant ATP levels had more
      rejection episodes (8/10) while patients with ATP levels in the low immune
      response had more infections (6/11) (P < .001; relative risk [RR] for rejection =
      1.2; RR for infection = 4.4). The mean ATP levels for rejection was 423.3 ng/mL
      versus 268.45 ng/mL for infection and 277.15 ng/mL for no events (ANOVA, P =
      .0145). Although acute rejections occurred mostly above 300, this was not
      significant (P = .059; RR = 0.9). Infections were more frequent with ATP under
      300 (RR = 7.3) and severe infection (endocarditis, meningitis, peritoneal
      abscesses, pneumonia, etc) were more frequent under 200 (P < .001). Comparing
      pretransplant with posttransplant values at the second week an increase
      correlated with rejection (P < .001, RR = 15.3), while a decrease did not
      correlate with the infection (P = .845, RR = 1.4). Patients who received
      antirejection treatment had a decrease in their ATP levels at 5 days (P = .002).
      CONCLUSION: This ATP release assays helpful in determining the risk of developing
      infection or rejection, as well as follow-up in the response to therapy.

PMID- 16647511
TI  - Cyclosporine-associated leukoencephalopathy in organ transplant recipients:
      experience of three clinical cases.
AB  - Leukoencephalopathy is a structural alteration of cerebral white matter mainly
      involving damage to myelin. Several reports have linked cyclosporine (CsA) with
      this alteration. The clinical features vary from qualitative alterations of
      consciousness to neurological deficits. Magnetic resonance imaging (MRI) of the
      brain demonstrates the damage to the white matter, which is essential for the
      differential diagnosis. We describe three clinical cases of leukoencephalopathy.
      The first case is a 43-year-old man received a cadaveric kidney transplant using
      immunosuppression with of mycophenolate mofetil, prednisone, and CsA. Four months
      later he developed meningism and bilateral sixth nerve palsy. The second case is
      a 50-year-old man with a cadaveric kidney transplant received immunosuppressive
      treatment with azathioprine and prednisone. As a result of gouty arthritis of the
      ankle, azathioprine was replaced with CsA to allow addition of allopurinol. Two
      weeks later he developed confusion and personality changes. The third case is a
      16-year-old man received a orthotopic liver transplant. Postoperatively he
      suffered generalized tonic-clonic seizures. In all patients the CsA levels were
      toxic and signs of neurological alterations were present on MRI. All patients
      recovered rapidly after CsA withdrawal.

PMID- 16647512
TI  - Utility of the MAYO End-Stage Liver Disease score, King's College Criteria, and a
      new in-hospital mortality score in the prognosis of in-hospital mortality in
      acute liver failure.
AB  - INTRODUCTION: Several prognostic scores attempt to aid in the selection of
      patients with acute liver failure (ALF) to be treated either medically or by
      liver transplantation; however, their lack of fulfillment does not predict
      spontaneous survival in ALF and refined prognostic criteria are needed to improve
      such selection. Our aim was to evaluate and compare a new ALF in-hospital
      mortality prediction score versus King's College Criteria (KCC) and model for End
      Stage Disease (MELD) score. METHODS: First-time ALF-diagnosed individuals
      admitted to our institution (n = 58) were grouped according their final outcome
      as "alive" or "death," and those significantly different variables between groups
      entered into a logistic regression and lineal regression models. An ALF in
      hospital mortality score (ALFIHMS) was produced and its sensitivity, specificity,
      and area under receiver operator characteristics were compared with those of KCC
      and MELD scores. RESULTS: Since no significant differences (P = .81) in mortality
      rates between fulminant and subfulminant hepatic failure were found, no further
      analysis according to ALF's classification was performed. After obtaining and
      comparing ALFIHMS with KCC and MELD, we found that ALFIHMS prediction accuracy is
      higher than that of KCC and MELD score and that an ALFIHMS cutoff point >15
      points is associated with an in-hospital mortality probability >50%. CONCLUSIONS:
      ALFIHMS has higher prognostic accuracy than KCC and MELD scores in ALF.

PMID- 16647513
TI  - Early posttransplant lymphoproliferative disease in pediatric liver transplant
      recipients.
AB  - Among 23 pediatric patients who underwent orthotopic liver transplant (OLT), we
      report two (11 and 26 months old) with posttransplant lymphoproliferative disease
      (PTLD) that occurred in the early posttransplantation period. They were Epstein
      Barr Virus (EBV)-negative and received graft from EBV-positive donors. The
      surveillance for EBV viremia using serial EBV polymerase chain reaction
      determinations in the peripheral blood was positive at 10 and 90 days after OLT
      concomitant with symptoms of primary infection, both patients were treated with
      gancyclovir. The patients should progression to a Burkitt's and a non-Hodgkin's
      lymphoma that appeared 3 months posttransplantation. They were treated by
      withdrawal of immunosuppression and six courses of cyclophosphamide as well as
      anti-CD20 monoclonal antibody (Rituximab) every 21 days. One patient experienced
      acute graft rejection, which resolved with steroids and low doses of tacrolimus,
      she is free of disease at 24 months after the end of treatment. The other patient
      relapsed with a cerebral lymphoma, receiving aggressive chemotherapy, but died
      due to sepsis. In conclusion, PTLD occurred among in 2/23 patients who underwent
      OLT and appeared in the first quarter post OLT. The risk factors associated with
      early PTLD were primary EBV infection after OLT, young age, and EBV-negative
      recipient receiving a transplant from an EBV-positive donor. Antiviral treatment
      alone was inefficient; withdrawal of immunosuppression and courses of Rituximab
      and cyclophosphamide were well tolerated and controlled PTLD. The risk of graft
      rejection was increased by withdrawal of immunosuppression. One patient died.

PMID- 16647514
TI  - Enteric-coated mycophenolate sodium experience in liver transplant patients.
AB  - Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as
      mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared
      to MMF its use in liver transplant patients has been limited. The purpose of this
      study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as
      a replacement for MMF in liver transplant patients. Ninety among 470 liver
      transplant recipients were receiving or had added an antimetabolite to their
      immunosuppressant therapy. The most common reason for this change was renal
      dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30
      months after liver transplantation. The mean administered daily dose was 720
      mg/d. At least one gastrointestinal symptom was reported by 25 patients.
      Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to
      be discontinued in two patients, while six others required dose reduction to
      resolve the symptoms. Hematological adverse events were infrequent: three
      patients had leukopenia and one, anemia, all of which responded to dosage
      reduction. There was a creatinine reduction within 6 months of drug commencement
      and maintenance of the lower creatinine levels at 1 year among patients who began
      EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and
      triglyceride levels were significantly lower among patients on EC-MPS than on
      MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile
      as MMF in liver transplant patients. Hematological and gastrointestinal adverse
      events were infrequent; seldom had the drug to be discontinued.

PMID- 16647515
TI  - Recommendations for use of everolimus after heart transplantation: results from a
      Latin-American Consensus Meeting.
AB  - Despite improvements during the last decades, heart transplantation remains
      associated with several medical complications, which limit clinical outcomes:
      acute rejection with hemodynamic compromise, cytomegalovirus (CMV) infections,
      allograft vasculopathy, chronic renal failure, and neoplasias. Everolimus, a
      proliferation signal inhibitor, represents a new option for adjunctive
      immunosuppressive therapy. Everolimus displays better efficacy in de novo heart
      transplant patients than azathioprine for prophylaxis of biopsy-proven acute
      rejection episodes of at least ISHLT grade 3A (P < .001), of allograft
      vasculopathy (P < .01), and of CMV infections (P < .01). These findings suggest
      that everolimus potentially play an important role as part of immunosuppressive
      therapy in heart transplant recipients. Heart transplant investigators from Latin
      America produced recommendations for everolimus use in daily practice based on
      available data and their own experience.

PMID- 16647516
TI  - Restoration of endocrine function and fertility with a tubo-ovarian
      autotransplant as the anatomical-functional unit in rabbits using a vascular
      microsurgical technique.
AB  - Infertility has been considered a global public health problem in many countries
      worldwide. Our objective was to restore endocrine function and fertility in tubal
      oophorectomized rabbits using an orthotopic tubal-ovarian vascularized
      autotransplant model as the anatomical-functional unit while employing a
      microvascular surgical technique. Twenty New Zealand white (NZW) sexually mature
      female rabbits and four male NZW rabbits of proven fertility were divided into
      two study groups. In group I (n = 10), a left salpingo-oophorectomy was
      performed. Group II (n = 10) was subjected to a bilateral salpingo-oophorectomy,
      plus a right orthotopic tubal-ovarian autotransplant. Our testing variables were
      vascular and tubal-anastomoses permeability, estradiol (E2) and progesterone (P4)
      serum levels, pregnancy, number of offspring, histopathological study of the
      uteri, fallopian tubes, and ovaries. One hundred percent immediate permeability
      of the tubal anastomoses was achieved, while late permeability was found to be
      64%. Immediate permeability of vascular anastomoses was 90%, and late
      permeability was recorded at 80%. E2 serum levels in both groups at different
      times showed no statistically significant differences. In the case of P4, a small
      difference was found during pregnancy, especially greater in the control group (P
      < .05). In the autotransplanted group, four rabbits became pregnant (44%).
      Endocrine function and fertility were restored in the rabbits with the tubal
      ovarian transplant as the anatomical-functional unit. The use of isotransplants
      and allotransplants should be considered a therapeutic alternative in the
      infertile woman with irreparable bilateral tubal damage, ovarian dysgenesis,
      surgical absence of ovaries and fallopian tubes, or when the conventional IVF/TE
      in these cases has been unsuccessful.

PMID- 16647517
TI  - Restoration of endocrine function and ovulation after a heterotopic ovarian
      transplant in the inguinal region of rabbits using a vascular microsurgical
      technique.
AB  - The aim of this study was to define an experimental model in rabbits for
      subcutaneous heterotopic ovarian autotransplants and allotransplants in the
      inguinal region using a microvascular technique to restore endocrine function and
      ovulation. Forty sexually mature New Zealand white receptor rabbits and 20
      donating Californian rabbits were divided into two experimental models: model A;
      autogenic model-control group 1 (n = 10), right ovariectomy; group II (n = 10),
      heterotopic ovarian autotransplant with peritoneal pouch plus left ovariectomy;
      model B: allogenic model-donator group III (n = 10), right ovariectomy with
      peritoneal tissue; receptor group (n = 10), ovarian heterotopic allotransplant
      with peritoneal pouch and bilateral ovariectomy, without immunosuppression; group
      IV donator (n = 10), receptor (n = 10) using the same procedure as in group III,
      administering cyclosporine 4 mg/kg/d intramuscularly and prednisone 1 mg/kg/d PO
      for 28 days. Ovarian function was assessed in the transplanted ovary after
      stimulation with human chorionic gonadotropin (100 IU). Exfoliative vaginal
      cytology was done, serum estradiol (E2) and progesterone (P(4)) were measure, and
      a histological study of ovaries and uteri was done. Late vascular permeability
      was 73.3%. Serum E2 and P4 levels during the poststimulation period were
      extremely low exclusively in group III (P < .05). In all viable grafts, the
      histological study showed follicular development and presence of luteal bodies.
      In the uteri, the endometrium was proliferative and vaginal cytology showed the
      karyopicnotic index was >20%. Endocrine function and ovulation were restored in
      the heterotopic transplanted ovary. Allogenic heterotopic ovarian transplants are
      indicated in women with gonadal dysgenesia or premature surgical menopause.

PMID- 16647518
TI  - Compensatory lung growth in autologous lobar implant: experimental study in dogs.
AB  - BACKGROUND: The best way to study compensatory lung growth (CLG) is in a
      transplant without rejection. Since immunosuppressive drugs may influence CLG, it
      is better to not use them. Therefore we studied CLG in a reimplant of only one
      lobe after its removal. The objective was to compare lobar transplant CLG with
      CLG after lobectomy. METHODS: Forty eight dogs were distributed in three groups:
      G1 = control, G2 = left cranial lobectomy, and G3 = left pneumonectomy with
      reimplantation of the caudal lobe. Five months after surgery the animals
      underwent lung scintigraphy and were sacrificed for morphometric study. RESULTS:
      There was no correlation between scintigraphy and lung mass or lung volume. There
      was both mass and residual volume CLG in the operated groups, both contralateral
      and ipsilateral to surgery. There was no compensation for total lung capacity or
      compliance in the remaining caudal lobe (G2) or the reimplanted caudal lobe (G3)
      at 5 months after surgery. There was more damage in the reimplanted lobe. As
      previous studies have shown that CLG starts with increased mass and residual
      volume and compliance is compensated later. This study seemed to document the
      beginning of CLG, with lung compliance being the limiting factor of CLG at 5
      months. CONCLUSION: There was CLG in both the reimplanted lobe and the
      contralateral lung, but compliance was still reduced. CLG was similar in both
      groups, but in the implanted lobe compliance was more prejudiced.

PMID- 16647519
TI  - Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic
      liver transplantation with portal vein arterialization in pigs.
AB  - OBJECTIVE: Our aim was to evaluate liver graft integrity and function using
      scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic
      liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND
      METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal
      echogenicity, portal and arterial anatomy, and portal and biliary system flow.
      Two types of scintigraphy were performed: microaggregated human albumin colloid
      scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both
      labeled with 99mTc. RESULTS: The animals were distributed into two groups. The
      first group consisted of three animals with clinical suspicion of graft
      dysfunction, in which the ultrasonographic study revealed areas of parenchymal
      destructuring. In the scintigraphic study, heterogenous uptake was observed;
      there was no uptake in one animal. Necropsy of these three animals revealed areas
      of graft necrosis. The second group consisted of five animals with good clinical
      evolutions, in which the ultrasonographic study showed portal dilation, portal
      flow with arterial spiculations, and homogenous echogenicity of the hepatic
      parenchyma. The scintigraphic study revealed homogenous uptake by the graft and
      an elimination speed of the hepatobiliary agent similar to that of the native
      liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of
      poor prognosis indicating necrosis in the same way as heterogenous uptake or
      nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to
      evaluate biliary function and bile elimination. In an AHLT-PVA, the main
      ultrasound findings derived from arterialization were dilation of the portal
      system and portal flow with arterial spiculations.

PMID- 16647520
TI  - Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem
      cells circulate in large amounts under the influence of acute large skin damage:
      new evidence for their use in regenerative medicine.
AB  - OBJECTIVES: Recent work has shown that human bone marrow contains mesenchymal
      stem cells (MSCs). However, little is known about their presence in peripheral
      blood. Since these cells are potentially responsible for tissue repair after
      injury, their number should be increased during these situations. To demonstrate
      their number during these situations, we measured MSCs in the peripheral blood of
      healthy donors and burn patients. MATERIALS AND METHODS: Blood samples were
      obtained from 15 acute burn patients and 15 healthy donors. We performed flow
      cytometric analysis, using a large monoclonal antibody panel: CD44, CD45, CD14,
      DR, CD34, CD19, CD13, CD29, CD105, CD1a, CD90, CD38, CD25. MSC phenotype was
      considered positive for CD44, CD13, CD29, CD90, and CD105, and negative for the
      other monoclonals. The testing was performed on day 3 after injury. We correlated
      the results with the age, sex, and size and type of burns. RESULTS: Cells
      expressing the MSC phenotype were detected in the peripheral blood of both
      groups. Noteworthy, compared with samples from healthy donors (0.0078 +/-
      0.0044), blood obtained from burn patients showed a higher MSC percentage (0.1643
      +/- 0.115; P < .001). The percentage of MSCs correlated with the size and
      severity of the burn. Increased values were also observed among younger patients.
      CONCLUSIONS: MSCs have an important role in regenerative processes of human
      tissues. We found cells phenotypically identical to MSCs circulating in
      physiological number in normal subjects, but in significantly higher amounts
      during acute large burns. Therefore, they may represent a previously unrecognized
      circulatory component to the process of skin regeneration.

PMID- 16647521
TI  - Nitrogen removal from on-site treated anaerobic effluents using intermittently
      aerated moving bed biofilm reactors at low temperature.
AB  - On-site post-treatment of anaerobically pre-treated dairy parlour wastewater
      (DPWWe; 10 degrees C) and mixture of kitchen waste and black water (BWKWe; 20
      degrees C) was studied in moving bed biofilm reactors (MBBR). The focus was on
      removal of nitrogen and of residual chemical oxygen demand (COD). Moreover, the
      effect of intermittent aeration and continuous vs. sequencing batch operation was
      studied. All MBBRs removed 50-60% of nitrogen and 40-70% of total COD (CODt).
      Complete nitrification was achieved, but denitrification was restricted by lack
      of carbon. Nitrogen removal was achieved in a single reactor by applying
      intermittent aeration. Continuous and sequencing batch operation provided similar
      nitrogen and COD removal, wherefore simpler continuous feeding may be preferred
      for on-site applications. Combination of pre-treating upflow anaerobic sludge
      blanket (UASB) -septic tank and MBBR removed over 92% of CODt, 99% of biological
      oxygen demand (BOD7), and 65-70% of nitrogen.

PMID- 16647522
TI  - Levels of evidence in otolaryngology journals.
AB  - OBJECTIVE: To identify trends in clinical research and levels of evidence in
      otolaryngology journals. STUDY DESIGN AND SETTING: We reviewed all original
      research articles from 1993, 1998, and 2003, in 4 major otolaryngology journals.
      Levels of evidence were graded 1 (strongest) through 5 (weakest). RESULTS: Of
      2584 total articles, 1924 (75%) were clinical research. During the study period,
      there was increased median sample size (from 22 to 30, P=0.06), more planned
      research (from 30% to 37%, P=0.023), more internal control groups (from 36% to
      43%, P=0.011), and more articles with P values (from 26% to 45%, P<0.001) or
      confidence intervals (from 1.2% to 7.6%, P<0.001). Most evidence was level 4
      (57%), but median levels increased slightly over time (P=0.027). Therapy articles
      had the weakest evidence (80% levels 3 to 5) and diagnostic test assessments had
      the strongest (75% levels 1 and 2). CONCLUSION: Although clinical research
      increased in quantity and quality, sample sizes were modest, most articles lacked
      controls, and confidence intervals were rare. Therapy articles would benefit from
      higher evidence levels. SIGNIFICANCE: By defining the current levels of evidence
      in otolaryngology journals, this overview should help guide future efforts.

PMID- 16647523
TI  - Development of a murine model of chronic rhinosinusitis.
AB  - OBJECTIVE: The aim of this study was to develop a mouse model of chronic
      eosinophilic rhinosinusitis. STUDY DESIGN: Mice were sensitized to Aspergillis
      fumigatus (Af) extract by intraperitoneal injection. The animals subsequently
      received nasal challenges with Af extract 3 times per week for 12 weeks.
      Sinonasal complexes were studied histologically by the study otolaryngologists
      and pathologists to characterize the inflammatory response. SETTING: Animal care
      facility at an academic institution. RESULTS: A chronic eosinophilic inflammatory
      response was evoked in all study animals. Statistical analysis was performed for
      inflammation, secretory cell hyperplasia, mast cells, and eosinophils. There were
      very significant differences (P<0.0005) between control and study mice in all
      categories. CONCLUSION: Prolonged nasal challenge of Af extract creates an
      inflammatory response in murine nasal mucosa that mimics human chronic
      eosinophilic rhinosinusitis. SIGNIFICANCE: A murine model for chronic
      rhinosinusitis is reported that may facilitate future investigations into disease
      pathophysiology. EBM RATING: B-2.

PMID- 16647525
TI  - Intracranial complications of pediatric sinusitis.
AB  - OBJECTIVE: To study intracranial extension of pediatric sinusitis, an infrequent
      but potentially fatal complication. STUDY DESIGN AND SETTING: Ten-year
      retrospective review at a tertiary children's hospital identified 21 cases of
      intracranial complications of sinusitis. RESULTS: Thirteen males and eight
      females with mean age of 13.3 years were identified. Overall 18 of 21 (81%)
      exhibited abscess formation, most commonly epidural. Only 3 of 21 (14%) had
      meningitis alone. All but 4 patients were managed surgically, requiring
      craniotomy in 13 of 21 (61.9%) and endoscopic sinus surgery (ESS) in 10 of 21
      (48%). Seven patients (33%) required multiple operations during admission.
      Nineteen patients (90%) had a total of 30 organisms cultured. Oral flora was
      observed in 12 of 21 (57%). Polymicrobial infections, seen in 9 of 21 (43%), were
      significantly associated with the need for craniotomy (P=0.02). Mean hospital
      stay was 15 days, and mean length of IV antibiotic was 5 weeks. CONCLUSIONS:
      Intracranial complications of pediatric sinusitis often require craniotomy. Oral
      flora and polymicrobial infections were prominent in this series. EBM RATING: C
      4.

PMID- 16647526
TI  - Improvements in quality of life in children after surgical therapy for sinonasal
      disease.
AB  - OBJECTIVES: To study changes in quality of life in children with chronic
      sinonasal disease after surgical therapy. STUDY DESIGN AND SETTING: Prospective,
      nonrandomized quality of life study of children with sinonasal disease who
      undergo adenoidectomy or functional endoscopic sinus surgery (FESS) at an
      academic institution. Caregivers completed a preoperative SN-5 quality of life
      survey and a second survey within 6 months after surgery. RESULTS: Twenty-two
      children were enrolled in the study (mean, 6.5 years; range, 1.4 to 15.9). The
      majority (59%) of children underwent adenoidectomy. The mean total score was 25.8
      at initial presentation and 12.0 at follow-up (P>0.001). Postoperative scores for
      all domains were significantly different from preoperative scores. The domains
      with the greatest change in mean score were nasal obstruction and emotional
      distress. There were no significant differences in outcome between children who
      underwent adenoidectomy and those who underwent FESS. CONCLUSIONS: After either
      adenoidectomy or FESS, caregivers report a dramatic improvement in the quality of
      life of children with sinonasal disease. EBM RATING: B-3b.

PMID- 16647527
TI  - Nasal health in Down syndrome: a cross-sectional study.
AB  - OBJECTIVE: To investigate peripheral nasal pathology as a contributor to
      olfactory impairment in DS. STUDY DESIGN: Twenty DS and 16 non-DS subjects were
      recruited. Nasal history and symptoms were assessed by self-report or informant.
      Olfactory threshold, odor identification, and nasal endoscopy were assessed on
      each subject. RESULTS: DS subjects were impaired on olfactory threshold
      (P<0.0001) and odor identification (P<0.001). Although DS subjects tended toward
      upper-respiratory infections, sleep-disordered breathing, and nasal itching,
      differences were not significant (P=0.07, 0.06, and 0.058, respectively). There
      were no significant differences on self-reported nasal history or symptoms.
      Endoscopy showed equivalent health in DS and control subjects. CONCLUSION: This
      DS population shows olfactory impairment. However, nasal health is comparable in
      DS subjects and controls. Nasal dysfunction is unlikely to contribute to
      olfactory impairment in DS. SIGNIFICANCE: Olfactory deficits in DS appear to be
      secondary to central, rather than rhinologic, pathology. EBM RATING: B-2b.

PMID- 16647528
TI  - Modulation of immune mediators with MQT-based immunotherapy.
AB  - OBJECTIVE: Assess immune and clinical changes with immunotherapy based on
      modified quantitative testing (MQT). BACKGROUND: Immunotherapy promotes
      immunomodulation that occurs over several years. Quantitative testing offers the
      advantage of initiating immunotherapy with robust antigen concentrations. This
      study assessed whether changes in immune mediators and allergy symptoms occur
      rapidly using quantitative techniques. METHODS: Sixteen allergic adults were
      tested using MQT. Subjects had serum drawn for immunoglobulins E and G4 (IgE,
      IgG4) to 3 antigens, Der p1, Der f1, and Fel d1, and for interleukins IL-1beta,
      IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13, and IL-1 receptor antagonist (IL-1RA).
      Subjects also completed the Sino-Nasal Outcome Test-20 (SNOT-20), the Allergy
      Outcome Scale (AOS), and the Rhinosinusitis Disability Index (RSDI). They
      underwent MQT-based immunotherapy and completed outcome measures again at 6 and
      12 weeks. RESULTS: Nine subjects completed the study. Analysis demonstrated
      significant increases in IgG4 levels to all antigens, significant decreases in
      serum levels of IL-1beta and IL-5, and significant increases in levels of IL-1RA.
      Improvement was also noted in AOS and RSDI subscales. CONCLUSION: Immunotherapy
      based on MQT demonstrates significant changes in immunoglobulin and cytokine
      levels by 12 weeks following initiation. In addition, improvement in symptom and
      quality-of-life measures occurs by 12 weeks. These findings support the rapid
      onset of clinical effects with MQT-based treatment of inhalant allergy. EBM
      RATING: C-4.

PMID- 16647529
TI  - Effects of topical application of methotrexate on nasal mucosa in rats: a
      preclinical assessment study.
AB  - OBJECTIVE: The aim of this study is to investigate dose-dependent effect of the
      topical application of methotrexate (MTX) in rats on the normal nasal mucosa,
      liver tissue, liver enzymes, and hemoglobin levels. STUDY DESIGN: Preclinical
      animal study. SETTING: Twenty male adult wistar albino rats were randomly divided
      into 4 groups (n=5). A single puff of MTX (2.5 microg) was applied to both nasal
      cavities 2 times a day. The animals were given MTX 1 day a week in group 1, 3
      days a week in group 2, and 5 days a week in group 3. Control group animals were
      given 1 puff of physiologic saline to both nasal cavities 5 days a week and 2
      times a day. After 28 days, liver biopsies, blood samples, and 5 nasal mucosal
      biopsies were taken. Histological examination was made with respect to certain
      parameters semiquantitatively (grade 0-3). The aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT) levels and hemoglobin counts were studied from
      blood samples. RESULTS: There are no statistically significant differences with
      respect to histopathological parameters between the control group and the groups
      1-3 (P>0.05). Histopathological examination of liver tissue did not reveal any
      evident difference between the control and study groups. Mean AST and ALT as
      liver function tests and hemoglobin counts were within normal limits. Topical
      application of MTX at these doses has no toxic effect on the nasal mucosa, the
      liver tissue, AST and ALT levels, and hemoglobin level. CONCLUSIONS: These
      results have been encouraging to investigate use of the topical application of
      MTX in nasal manifestation of autoimmune disease or addition of the topical
      application of MTX to the steroid treatment in cases with massive nasal polyposis
      resistant to steroids and prone to recurrence.

PMID- 16647530
TI  - Snoring significance in patients undergoing home sleep studies.
AB  - OBJECTIVE: To analyze the impact of snoring, independent of obstructive sleep
      apnea syndrome on patients referred for home sleep studies and to report a new
      technology for the reporting of snoring, using sophisticated sound collection and
      noise-canceling technology. STUDY DESIGN AND SETTING: A retrospective statistical
      review of consecutive anonymous data compiled from questionnaires and digital
      data of snoring loudness and duration measured at the upper lip during unattended
      home sleep studies in 4,860 patients referred for snoring and sleep-disturbed
      breathing. RESULTS: A strong relationship exists between a history of snoring and
      complaints of daytime sleepiness (80%), obesity (73%), and chronic fatigue (78%)
      (all yield P<0.001). By contrast, only 42% to 48% of patients without these
      symptoms complain of snoring. In 3 multiple-regression analyses, the percent of
      time snoring, average loudness, and peak loudness are all significantly predicted
      by the apnea hypopnea index (all P<0.003), body mass index (all P<0.001), and age
      (P=0.014). Daytime sleepiness was strongly predicted by percent time snoring
      (P=0.014), weakly by average loudness (P=0.046), and not at all by peak loudness
      (P=0.303). CONCLUSION: By using a pair of microphones placed at the upper lip,
      one that samples breath sounds and the other ambient sound and artifact noise,
      the NovaSOM QSG measures snoring while canceling ambient noise. The clinical
      impact of snoring on the patient as well as the bed partner, independent of
      obstructive sleep apnea syndrome, is an unrecognized factor in sleep-disturbed
      breathing. SIGNIFICANCE: Measurable criteria to define snoring are suggested.
      Snoring loudness is not measured in most laboratory Polysomnograms. EBM RATING: B
      3b.

PMID- 16647531
TI  - Histopathologic parameters as predictors of response to endoscopic sinus surgery
      in nonallergic patients with chronic rhinosinusitis.
AB  - OBJECTIVE: To estimate the predictable value of histopathologic parameters in
      chronic rhinosinusitis (CRS) for response to endoscopic sinus surgery (ESS).
      STUDY DESIGN: Symptomatology was rated in 100 patients prior to as well as 12 and
      24 months after surgery. Specimens taken during the procedure were examined and
      scored for goblet cells, subepithelial thickening, mast cells, and eosinophils.
      Multiple regression analysis was performed to predict the total score of
      subjective symptoms before treatment by histopathologic parameters. The
      correlation between histopathologic parameters and postoperative symptoms was
      then evaluated. RESULTS: Goblet cells were the best predictor correlating with 5
      symptoms. Subepithelial thickening correlated with 4 symptoms. Mast cell
      infiltration correlated with 3 symptoms. Eosinophilic infiltration correlated
      with only one symptom (P<0.05). CONCLUSION: Certain histopathologic parameters in
      CRS are predictive of favorable response to ESS. SIGNIFICANCE: Pathologic
      evaluation may help the ENT surgeon to predict the persistence of certain CRS
      symptoms after ESS, even in patients at low risk for surgical failure. EBM
      RATING: C-4.

PMID- 16647532
TI  - Adult spontaneous CSF otorrhea: correlation with radiographic empty sella.
AB  - OBJECTIVE: To determine the prevalence of radiographic empty sella in patients
      with spontaneous cerebrospinal fluid (CSF) otorrhea. STUDY DESIGN AND SETTING:
      Retrospective case series of adult patients with CSF otorhinorrhea at an academic
      tertiary medical center. Patients with history of skull base surgery, trauma,
      tumor, or chronic ear disease were excluded. Available imaging studies were
      reviewed with attention to the sella turcica. RESULTS: Eight patients were
      diagnosed with spontaneous CSF otorrhea. Five of seven patients with adequate
      imaging studies (71%) had a radiographic empty sella. Seven of eight patients
      were clinically obese, with a body mass index BMI>30 kg/m2. CONCLUSIONS: Empty
      sella is a common radiologic finding in patients with spontaneous CSF otorrhea.
      This supports the theory that increased intracranial pressure contributes to
      development of spontaneous CSF otorrhea. SIGNIFICANCE: Radiographic empty sella
      predicts elevated intracranial pressure, which may require further evaluation and
      treatment in patients with spontaneous CSF otorrhea. EBM RATING: C-4.

PMID- 16647533
TI  - Helicobacter pylori: a possible association with otitis media with effusion.
AB  - OBJECTIVE: Evaluate possible role of Helicobacter Pylori in pathogenesis of
      otitis media with effusion (OME). STUDY DESIGN AND SETTING: Randomized controlled
      trial, tertiary referral center. STUDY GROUP: Middle ear fluid was aspirated, a
      biopsy was taken from the promontorium of 22 children with OME. CONTROL GROUP: A
      small biopsy was taken from the promontorium of 20 children with normal otologic
      findings. For both groups, 5 mm deep tissue specimens were obtained from tonsil
      and adenoid. RESULTS: H pylori presence in the middle ear, the tonsillar and
      adenoid tissues by culture and PCR was significantly more frequent in the study
      group compared to the control group (P<0.05). CONCLUSIONS: This study is the
      first to grow H pylori in middle ear in OME. Significantly increased colonization
      by H pylori of the middle ear, and tonsillar and adenoid tissue in patients with
      OME indicates that the bacteria might be involved in the pathogenesis of OME. EBM
      RATING: A-1b.

PMID- 16647534
TI  - Image-guided localization of the internal auditory canal via the middle cranial
      fossa approach.
AB  - OBJECTIVE: We sought to determine the accuracy of an electromagnetic image
      guidance surgical navigation system in localizing the midpoint of the internal
      auditory canal (IAC) and other structures of the temporal bone through the middle
      cranial fossa approach. MATERIALS AND METHODS: Seven fresh cadaveric whole heads
      were dissected via a middle cranial fossa approach. High-resolution CT scans were
      used with an InstaTrak 3500 Plus electromagnetic image guidance system (General
      Electric, Fairfield, CT). We evaluated the accuracy of identifying several middle
      cranial fossa landmarks including the midpoint of the IAC; the labyrinthine
      segment of the facial nerve; and the arcuate eminence, the carotid artery, and
      foramen spinosum. RESULTS: We were able to identify the middle of the IAC within
      2.31 mm (range 0.65-7.52 mm, SD 2.39 mm). The arcuate eminence could be
      identified within 1.86 mm (range 1.49-2.37 mm, SD 0.36 mm). We noted some
      interference when the handpiece was within 6 to 8 cm of the microscope.
      CONCLUSION: Although computer-aided navigational tools are no substitute for
      thorough knowledge of temporal bone anatomy, we found the InstaTrak system
      reliable in identifying the midpoint of the IAC to within 2.4 mm through a middle
      fossa approach.

PMID- 16647535
TI  - Evaluation of super-high-dose steroid therapy for sudden sensorineural hearing
      loss.
AB  - OBJECTIVE: To determine the efficacy of a high-dose steroid regimen for patients
      with sudden sensorineural hearing loss (SSNHL) and to evaluate the relationship
      between outcome and initial steroid dose. STUDY DESIGN AND SETTING: We conducted
      a retrospective study of 112 patients presenting to Saitama Medical Center.
      Patients received tapering courses of hydrocortisone (HC) with an initial dose of
      either 1200 mg or 600 mg. RESULTS: More than 87% of patients had recovery of
      hearing. When hearing stabilized, there were no significant differences between
      the 1200 mg and 600 mg groups in terms of hearing outcome (P>0.05). However, at
      completion of treatment, the 1200 mg group exhibited significantly superior
      complete recovery rate and improvement rate (P<0.05). CONCLUSION: Application of
      our treatment protocol of a tapered course of 1200 mg HC significantly and
      rapidly improves recovery outcomes in patients of SSNHL. EBM RATING: C-4.

PMID- 16647536
TI  - Gerbilline cholesteatoma development Part I: Epithelial migration pattern and
      rate on the gerbil tympanic membrane: comparisons with human and guinea pig.
AB  - OBJECTIVE: To determine the migration rate and pattern for keratin on the
      tympanic membrane (TM) of the gerbil and guinea pig in comparison to human data
      and determine which species is an appropriate model for investigating the
      relationship of epithelial clearance to cholesteatoma formation. STUDY DESIGN AND
      SETTING: Ink drops were placed on the TM and their locations plotted daily.
      RESULTS: Gerbils demonstrated a radial migration pattern away from the umbo,
      identical to that reported for humans, although the rate was 0.32 mm/day-3 times
      the human rate of 0.1 mm/day. Guinea pigs were significantly different from
      gerbils and humans, with a rate of 0.79 mm/day and a pattern of superior/inferior
      migration without anterior-posterior movement. CONCLUSION: Gerbils more closely
      resemble humans in rate and pattern of epithelial migration. SIGNIFICANCE:
      Gerbils represent the most appropriate model for determining the relationship
      between keratin migration and cholesteatoma formation.

PMID- 16647537
TI  - A survey of parental views regarding their child's hearing loss: a pilot study.
AB  - OBJECTIVE: Assess parental perceptions of their child's sensorineural hearing
      loss care. METHODS: Families of pediatric patients diagnosed with a sensorineural
      hearing loss from 2000 to 2004 were sent a survey asking about their experiences
      with their child's hearing loss. RESULTS: One hundred eight of 389 families
      surveyed were studied. Thirteen percent did not know the results of the newborn
      screening. Twenty-two percent of the primary care physicians were not involved in
      the child's hearing evaluation. Forty percent of the patients underwent 4 or more
      audiologic tests before a diagnosis. The most common reason for delayed diagnosis
      was difficulty in obtaining an appointment with an audiologist. Sixty-two percent
      of families had difficulties obtaining hearing aids, and 58% noted difficulties
      obtaining cochlear implants. CONCLUSIONS: Families reported multiple obstacles to
      obtain timely diagnosis and treatment. Otolaryngologists may need to be more
      involved in the evaluation and treatment of these patients. EBM RATING: C-4.

PMID- 16647538
TI  - Intraoperative cone-beam CT for guidance of temporal bone surgery.
AB  - OBJECTIVES: To describe our preclinical experience with Cone Beam CT (CBCT) in
      image-guided surgery of the temporal bone. STUDY DESIGN AND SETTINGS: A mobile
      isocentric C-arm (PowerMobil, Siemens Medical Systems, Erlangen, Germany)
      modified to include a flat-panel detector (Varian Imaging Products, Palo Alto,
      CA) and a motorized orbit was developed to acquire multiple projections in
      rotation about a subject. Initial experiments imaging steel wire in air were used
      to investigate the system's spatial resolution in 3D image reconstruction.
      Subsequently temporal bone dissection was performed on five cadaver heads using
      the modified C-arm as an image guidance system. RESULTS: We obtained a spatial
      resolution of 0.85 mm. The image acquisition time was 120 seconds and the
      radiation dose approximately one-tenth of a conventional CT scan. CONCLUSION:
      CBCT provided submillimeter accuracy at high speed with low radiation dosage to
      offer utility as an intraoperative imaging system. SIGNIFICANCE: CBCT offers
      technology that approximates "near-real-time" image guidance. EBM RATING: C-4.

PMID- 16647539
TI  - Sudden sensorineural hearing loss: long-term follow-up results.
AB  - OBJECTIVE: This study describes the long-term outcome of patients suffering from
      sudden sensorineural hearing loss (SSHL) after an initial combined therapy of
      steroids with vasodilators. STUDY DESIGN AND SETTING: Eighty cases were
      retrospectively reviewed to evaluate the long-term audiometric data and to
      statistically assess the value of specific clinical parameters. The persistent
      long-term otoneurologic manifestations associated with SSHL were also reported.
      RESULTS: In the long-term period, hearing level remained stable 2 months after
      the onset of SSHL. Patients complained of persistent tinnitus (36%), fluctuant
      hearing loss (8.7%), dizziness (8.7%), and classical Meniere's triad in 2.5% of
      cases. Profound and total SSHL associated with vertigo are poor prognostic
      indicators. CONCLUSIONS: In terms of cost-effectiveness, a steroid-vasodilator
      therapy for SSHL for >2 months is not recommended because no additional effect
      was evidenced. Persistent otoneurologic manifestations, mainly tinnitus or
      dizziness are relatively common, particularly in patients with severe to total
      SSHL. EBM RATING: C-4.

PMID- 16647540
TI  - Stapedectomy in congenital stapes fixation: are hearing outcomes poorer?
AB  - OBJECTIVE: To evaluate outcomes of stapedectomy surgery for congenital stapes
      fixation. STUDY DESIGN: Retrospective chart review. METHODS: The charts of 463
      stapedectomies performed by 1 surgeon from 1996 to 2003 were reviewed. Patients
      with a history of childhood hearing loss and operative findings consistent with
      congenital fixation of the stapes were included. Patients with a history of
      trauma or chronic otitis media and those with otosclerosis were excluded. Thirty
      six patients underwent stapedectomy for congenital fixation. Revision cases and
      those with inadequate postoperative bone or air conduction data were excluded.
      Inclusion criteria were met for 25 patients. Operative findings and hearing
      outcomes were evaluated. RESULTS: The study group was comprised of 25
      stapedectomies. Closure of the air-bone gap to less than 10 dB was achieved in
      48% of cases, and 80% had closure within 20 dB. A gap of more than 30 dB remained
      in 3 cases. There were 2 cases of sensorineural hearing loss with worsening of
      the bone conduction thresholds by 15 dB and 30 dB. There were no instances of
      perilymph gusher. In addition to an excluded case that was not reconstructed
      because of facial nerve position, 3 of the included patients were found to have a
      dehiscent facial nerve at surgery. There were no facial nerve injuries, and
      fixation of the malleus or incus was not found in any of the included patients.
      When hearing outcomes were compared with our results for otosclerosis over the
      same time period, rates of closure to within 10 dB and 20 dB were significantly
      worse in the congenital group. CONCLUSION: Closure of the air-bone gap in this
      population differs from our results in stapedectomy done for otosclerosis. This
      difference likely reflects subtle anatomic variations in the congenital group
      that affect the effectiveness of the prosthesis. Despite the difference in
      results, stapedectomy for congenital fixation remains an effective method to
      achieve significant hearing improvement in the majority of patients. EBM RATING:
      B-3b.

PMID- 16647541
TI  - Invasive well-differentiated thyroid carcinoma: effect of treatment modalities on
      outcome.
AB  - OBJECTIVE: Well-differentiated thyroid carcinoma is considered an indolent
      malignant disease. Although rare, extrathyroidal invasion is associated with a
      worse prognosis and increased risk of morbidity. Management remains
      controversial, with some authors advocating conservative treatment with
      preservation of midline structures and others, aggressive extensive en bloc
      resection. The aim of this study was to report our 40-year experience with
      invasive thyroid carcinoma, with emphasis on the clinical characteristics and the
      effect of different treatment modalities on survival. STUDY DESIGN AND SETTING: A
      retrospective study including a file review of 1,200 patients with a diagnosis of
      well-differentiated thyroid carcinoma of whom 49 (5%) showed involvement of an
      adjacent structure (larynx, trachea and esophagus) (study group). Type of
      surgery, radiation treatment, radioiodine treatment, and patient demographics
      were evaluated. RESULTS: Compared to the rest of the patients, the study group
      was characterized by a higher rate of male patients (39% vs 25%), and older
      average age (58 vs 45 years). Average size of the primary tumor was 3.7 cm.
      Sixteen patients underwent radical surgery and 33 conservative surgery followed
      by radioiodine treatment. Five-year survival and recurrence rates for the whole
      group were 78% and 52%, respectively. The only statistically significant factor
      for survival was large tumor size. Distant metastases developed in 46% of
      patients, all in the lungs. Ten of 14 deaths were due to distant metastases.
      External radiation, used in 52% of the patients, was associated with worse
      prognosis. CONCLUSION: Conservative procedures followed by radioiodine treatment
      are associated with similar survival rates as aggressive techniques, with less
      perioperative mortality and lower overall morbidity. SIGNIFICANCE: This study
      provides further evidence that in cases of invasive thyroid tumors the extent of
      the primary surgery seems to have no influence on survival. EBM RATING: C-4.

PMID- 16647542
TI  - Reconstruction of circumferential oro- and hypopharyngeal defects with U-shaped
      pectoralis major myocutaneous flap.
AB  - OBJECTIVE: The purpose of the study was to evaluate the effectiveness of a U
      shaped pectoralis major myocutaneous flap (PMMF) to reconstruct a large
      circumferential defect involving the oro- and hypopharynx. STUDY DESIGN AND
      SETTING: Retrospective case series. RESULTS: Twelve patients with advanced oro-
      and hypopharyngeal cancer (stage IV) underwent surgery resulting in a
      circumferential defect of pharyngoesophageal segment (PES). Those defects were
      reconstructed using a U-shaped PMMF. Four pharyngocutaneous fistulas were
      observed postoperatively and healed spontaneously within 3 to 7 weeks. Eight
      patients were able to resume a regular diet. A voice prosthesis was functional in
      5 patients. CONCLUSION: This preliminary study shows that this technique is a
      simple and effective method with acceptable morbidity rate and satisfactory
      functional results. We demonstrate that this procedure allows the reconstruction
      of large defects involving the oro- and hypopharynx in irradiated patients. This
      technique could be an interesting alternative for surgical teams suffering from
      the absence of a microsurgical team. EBM RATING: C-4.

PMID- 16647543
TI  - Endoscopic laser vs open approach for cricopharyngeal myotomy.
AB  - OBJECTIVE: To illustrate the safety and efficacy of the endoscopic laser approach
      for cricopharyngeal myotomy (CPM) compared to the traditional transcervical
      approach. STUDY DESIGN AND SETTING: Retrospective chart review of 22 patients
      undergoing CPM from 1996 to 2003 at the Mayo Clinic, Jacksonville. RESULTS: The
      laser CPM technique was used in 14 patients, and an open approach in 8. The mean
      hospital stay and operative times were shorter for the laser group. Functional
      outcome analyses showed improvement in both groups. There were no major
      complications in the laser group, while 1 patient in the transcervical group had
      a pharyngocutaneous fistula. CONCLUSIONS: The laser technique is at least as
      effective as the transcervical approach for CPM to improve dysphagia symptoms in
      the properly selected patient, with a low risk of major complications.
      SIGNIFICANCE: In this report, we provide the reader with data to support the
      safety and efficacy of laser CPM. EBM RATING: B-3b.

PMID- 16647544
TI  - Laryngeal inflammation assessed using the reflux finding score in obstructive
      sleep apnea.
AB  - OBJECTIVES: To evaluate the relationships between laryngeal inflammation assessed
      using the Reflux Finding Score (RFS), laryngeal sensory function, and apnea
      severity in patients with obstructive sleep apnea (OSA). METHODS: Endoscopic
      sensory testing (EST) was performed with subsequent blinded scoring from video of
      RFS. An RFS>7 was indicative of increased inflammatory change. RESULTS: Of 34
      patients evaluated, 29 had OSA (apnea-hypopnea index [AHI]>or=15 events/h) at
      polysomnography. Increased inflammation was present in 26/29 (90%), with changes
      suggestive of laryngopharyngeal reflux. There were significant correlations
      between: inflammation and OSA severity (eg, RFS vs AHI, r=0.57, P<0.001);
      inflammation and laryngeal sensory impairment (EST detection threshold and
      pressure required to elicit the laryngeal adductor reflex, LAR); and the degree
      of sensory impairment and OSA severity. CONCLUSIONS: Laryngeal inflammation is
      prevalent among OSA patients and correlates with laryngeal sensory dysfunction,
      attenuation of the LAR, and apnea severity. EBM RATING: C-4.

PMID- 16647545
TI  - Local control of murine subglottis development.
AB  - OBJECTIVE: To determine if subglottic development is at least partially under
      local control and to determine which tissue layer(s) is predominantly
      responsible. DESIGN: The suglottises of 12 day-3 CD1 mice were grown in whole
      organ culture. The 12 subglottises were divided into 3 individual groups: +++, 
      ++, and ---. Group+++ had all tissue layers of the subglottis intact: luminal
      epithelium, cricoid cartilage, inner and outer perichondrium. Group-++ had all
      layers intact with the exception of luminal epithelium. Group--- had all layers
      removed (luminal epithelium, inner and outer perichondrium) resulting in cricoid
      cartilage-only rings. All rings were grown in basic medium without the use of
      growth factors or serum for 15 days. Measurements of the rings were taken before
      and after organ culture growth. RESULTS: Group+++ was the only group that
      experienced growth. Only luminal growth was statistically significant although
      all rings experienced growth in both the luminal and external diameter. Group-++
      did not experience any growth. Group--- lost structural integrity with collapse
      of the ring and did not experience growth of any dimension of the cartilage.
      CONCLUSIONS: Growth of the subglottis is under local control but may have
      additional influences from the outside that were not investigated here. Removal
      of just the epithelium stunts growth of the entire ring, but preferentially the
      lumen more so than the external diameter. Removal of all tissue layers around the
      cricoid cartilage results in a structural collapse of the ring, suggesting that
      the cartilage in this age group is dependent on surrounding tissues for
      structural integrity.

PMID- 16647546
TI  - Upper respiratory tract involvement of sarcoidosis in the Turkish population.
AB  - PRINCIPLES AND METHODS: Upper respiratory tract (URT) involvement is rare in
      sarcoidosis. In this descriptive study, we retrospectively evaluated the clinical
      and demographic features of 12 (2.19%) patients with URT involvement out of the
      546 sarcoidosis patients with follow-up visits at our center within the last 40
      year period. RESULTS: Out of the 546 patients, 12 (2.19%) had upper respiratory
      tract involvement, 5 (0.91%) had laryngeal involvement, 4 (0.73%) had sinonasal
      tract involvement, 2 (0.36) patients had salivary gland involvement, and 1
      patient had tonsillary involvement. The number of stage 0 subjects among other
      sarcoidosis patients was significantly lower than that among those with URT
      involvement. CONCLUSIONS: URT involvement is rarely diagnosed in patients with
      systemic sarcoidosis. The most common site for URT involvement among the Turkish
      population is the larynx, followed by the sinonasal tract. EBM RATING: C-4.

PMID- 16647547
TI  - Coblation adenotonsillectomy: an improvement over electrocautery technique?
AB  - OBJECTIVES: To compare postoperative complication rates of coblation and
      electrocautery adenotonsillectomies. STUDY DESIGN: Retrospective chart review.
      RESULTS: From January 2000 to June 2004, 1997 pediatric patients underwent
      adenotonsillectomy. 745 coblation, and 1252 electrocautery tonsillectomies were
      performed. Primary bleed, secondary bleed, and dehydration were seen in 3, 35,
      and 23 coblation, and 9, 41, and 64 electrocautery tonsillectomies, respectively.
      Data analysis revealed no significant difference in primary and secondary
      hemorrhage rate, but a higher dehydration rate in the electrocautery group
      (P=0.0423). A total of 602 coblation, 763 curette/cautery, and 632 electrocautery
      adenoidectomies were performed. Neck pain was seen in 0, 17, and 3 patients,
      respectively. Data analysis showed a higher incidence of neck pain with the
      curette/cautery technique compared with coblator and cautery techniques (P=0.0006
      and P=0.0119, respectively). CONCLUSIONS: Coblation tonsillectomy had similar
      rates of primary and secondary hemorrhage when compared with electrocautery
      tonsillectomy but a lower incidence of postoperative dehydration. Coblation
      adenoidectomy caused less postoperative neck pain than curette/cautery
      adenoidectomy without significant advantage over cautery adenoidectomy. EBM
      RATING: B-3b.

PMID- 16647548
TI  - The effect of hyoid suspension in a multilevel surgery concept for obstructive
      sleep apnea.
AB  - OBJECTIVE: This study investigated the outcome of the hyoid suspension as a part
      of a multilevel surgery protocol. STUDY DESIGN AND SETTING: Eighty-three patients
      with obstructive sleep apnea (OSA) underwent a multilevel surgical treatment
      because of continuous positive-airway pressure intolerance, 67 with the hyoid
      suspension and 16 without the hyoid suspension. All patients underwent a pre- and
      postoperative polysomnography in the sleep laboratory. RESULTS: The mean
      preoperative apnea hypopnea index (AHI) was 36.4+/-21.2 and 19.4+/-19.7
      postoperatively for all patients (P<0.0001). Further statistically significant
      changes were found for the arousal index, the oxygen saturation, and the daytime
      sleepiness. No statistically significant change was found for body mass index. In
      the group of patients treated without the hyoid suspension, the AHI did not
      decrease statistically significant. After surgery, 59.7% of the subjects with the
      hyoid suspension were regarded as cured. CONCLUSION: Multilevel surgery including
      the hyoid suspension is an effective treatment in subgroup of OSA patients. EBM
      RATING: C-4.

PMID- 16647549
TI  - Communication between functional and denervated muscles using radiofrequency.
AB  - OBJECTIVE: This article focuses on establishing communication between a
      functional muscle and a denervated muscle using a radiofrequency communications
      link. The ultimate objective of the project is to restore the eye blink in
      patients with facial nerve paralysis. STUDY DESIGN AND SETTING: Two sets of
      experiments were conducted using the gastrocnemius leg muscles of Sprague-Dawley
      rats. In the initial tests, varying magnitudes of voltages ranging from 0.85 to
      2.5 V were applied directly to a denervated muscle to determine the voltage
      required to produce visible contraction. The second set of experiments was then
      conducted to determine the voltage output from an in vivo muscle contraction that
      could be sensed and used to coordinate a signal for actuation of a muscle in a
      separate limb. After designing the appropriate external communication circuitry,
      a third experiment was performed to verify that a signal between a functional and
      a denervated muscle can be generated and used as a stimulus. RESULTS: Voltages
      below 2 V at a 10-millisecond pulse width elicited a gentle, controlled
      contraction of the denervated muscle in vivo. It was also observed that with
      longer pulse widths, higher stimulation voltages were required to produce
      sufficient contractions. CONCLUSION: It is possible to detect contraction of a
      muscle, use this to generate a signal to an external base station, and
      subsequently cause a separate, denervated muscle to contract in response to the
      signal. SIGNIFICANCE: This demonstration in vivo of a signaling system for pacing
      of electrical stimulation of 1 muscle to spontaneous contraction of another,
      separate muscle, using radiofrequency communication without direct connection,
      may be used in numerous ways to overcome nerve damage.

PMID- 16647550
TI  - CT-MR image fusion for the management of skull base lesions.
AB  - OBJECTIVE: Image fusion software creates composite images from computed
      tomography (CT) and magnetic resonance (MR) images. STUDY DESIGN AND SETTING: CT
      MR fusion studies between August 2004 to July 2005 were reviewed. CT scan images
      (1-mm axial) were obtained on a multi-detector CT scanner. MR images (1-mm axial)
      were obtained with a T1-weighted, volume acquisition technique. CT-MR fusion
      images were created on the Instatrak 3500 Plus or CBYON Suite. RESULTS: A total
      of 25 patients had 27 CT-MR image fusion studies. CT-MR fusion accuracy was 2 mm
      or better. During preoperative planning and intraoperative navigation, CT-MR
      fusion facilitated the delineation of the anatomic relationships between the
      lesion and the skull base. CONCLUSIONS: CT-MR image fusion yields composite
      images that combine features of each component imaging modality. Image fusion,
      when combined with surgical navigation, further enhances potential skull base
      applications for minimally invasive endoscopic surgery.

PMID- 16647551
TI  - Retinal detachment after subcranial resection of an anterior skull base tumor.

PMID- 16647552
TI  - Atypical solitary fibrous tumor of the larynx.

PMID- 16647553
TI  - Basaloid squamous cell carcinoma of the sinonasal tract: report of two cases.

PMID- 16647554
TI  - A case of angiosarcoma of the nasal cavity successfully treated with recombinant
      interleukin-2.

PMID- 16647555
TI  - Thyroid carcinoma presenting as a hot nodule.

PMID- 16647556
TI  - Cavernous hemangioma of the bony external auditory canal.

PMID- 16647557
TI  - Human cytomegalovirus infection of cells of hematopoietic origin: HCMV-induced
      immunosuppression, immune evasion, and latency.

PMID- 16647558
TI  - Earlier administration of Rituximab allows higher rate of long-lasting response
      in adult patients with autoimmune thrombocytopenia.

PMID- 16647559
TI  - CD27 expression in malignant and normal human B precursors: a confirmed
      phenomenon. Reply to Nilsson and colleagues.

PMID- 16647561
TI  - Comment on: HDL cholesterol levels are an important factor for determining the
      lifespan of erythrocytes. Exp Hematol 2005; 33(11):1309-1319.

PMID- 16647563
TI  - TGFbeta1 induces mast cell apoptosis.
AB  - Mast cells are potent effectors of the inflammatory response, playing an
      important role in atopy, bacterial immunity, and animal models of arthritis,
      multiple sclerosis, and heart disease. Hence controlling mast cell numbers and
      responsiveness is essential for preventing inflammatory disease. We demonstrate
      that the cytokine transforming growth factor (TGF) beta1 is a potent inducer of
      mast cell apoptosis, a finding that was consistent in cultured mouse bone marrow
      derived mast cells, peritoneal mast cells, and human mast cells. Cell death
      appeared to be caused by TGF-mediated repression of interleukin-3 (IL-3) receptor
      expression and function, leading to mitochondrial damage and activation of an
      apoptotic cascade acting via p53 and caspases. Although IL-3 receptor expression
      was reduced within 1 day of TGFbeta1 stimulation, apoptosis required at least 3
      days to occur. This delay in onset is postulated to allow protective mast cell
      effector functions, protecting the host from infection while preventing the
      establishment of chronic inflammation. Our data support the theory that TGFbeta1
      is an inhibitor of mast cell survival. The widespread expression of TGFbeta1
      offers this cytokine as an ideal candidate for control of mast cell homeostasis.

PMID- 16647564
TI  - Lentiviral vectors pseudotyped with murine ecotropic envelope: increased
      biosafety and convenience in preclinical research.
AB  - OBJECTIVE: Lentiviral vectors are increasingly used for preclinical models of
      gene therapy and other forms of experimental transgenesis. Due to the broad
      tropism and the ability for concentration by ultracentrifugation, most lentiviral
      vector preparations are produced using the vesicular stomatitis virus
      glycoprotein (VSV-g) protein as envelope. Recently, Hanawa and colleagues have
      demonstrated that the ecotropic envelope protein of murine leukemia viruses
      allows efficient pseudotyping of HIV-1-derived vector particles. However, this
      method has found little acceptance, despite potential advantages. MATERIALS AND
      METHODS: We produced lentiviral vectors pseudotyped with murine ecotropic
      envelope using a four-plasmid transient transfection system and evaluated their
      performance in murine fibroblasts and hematopoietic cells. RESULTS: Titers of
      lentiviral "ecotropic" supernatants were only slightly lower than those produced
      with VSV-g, could be concentrated by overnight centrifugation (13,000g), and
      efficiently transduced murine fibroblasts and hematopoietic cells but not human
      cells. Our Institutional Biosafety Committee agreed on the production and use of
      replication-defective lentiviral vectors pseudotyped with murine ecotropic
      envelope under biosafety level 1 (BL1) conditions with additional BL2 practices.
      We also obtained useful guidelines for the work with human infectious lentiviral
      vectors. CONCLUSIONS: For the researcher, "ecotropic" lentiviral vectors
      significantly improve the convenience of daily work, compared to the conditions
      required for lentiviral pseudotypes that are capable of infecting human cells.
      High efficiency and superior biosafety in combination with convenient handling
      will certainly boost the potential applicability of this important vector system.

PMID- 16647565
TI  - The anemia of "haemoglobin-deficit" (hbd/hbd) mice is caused by a defect in
      transferrin cycling.
AB  - OBJECTIVE: The hemoglobin-deficit mouse mutant (hbd) is characterized by a
      hypochromic, microcytic anemia that is inherited in an autosomal, recessive
      manner. The recently identified gene responsible, Sec15l1, is specific to
      hematopoietic stem cells and is homologous to a gene encoding a member of the
      exocyst pathway in yeast. However, the defective cellular mechanism underlying
      the hemoglobin deficiency in hbd/hbd mice has not been functionally identified.
      Here we investigated the possibility that erroneous transferrin trafficking is
      responsible for the hbd phenotype. MATERIALS AND METHODS: Reticulocytes were
      harvested from hbd/hbd mice and from background- and age-matched controls. Iron
      and transferrin uptake and iron utilization experiments were performed using 59Fe
      or 125I-transferrin to follow the trafficking and utilization of the protein and
      metal. RESULTS: Compared to controls, iron and transferrin uptake as well as iron
      incorporation into heme was compromised in hbd reticulocytes. Importantly,
      reduced heme synthesis in these cells was restored to normal values by using an
      iron source that bypasses the transferrin-receptor pathway. We also found that
      +/+ and hbd reticulocytes take up free, ferrous iron at identical rates, while
      the rates of Tf internalization and externalization were significantly decreased
      in the mutant cells. Finally, utilization of endosomal radioiron was likewise
      deficient in the hbd reticulocytes. CONCLUSION: Our results indicate that heme
      biosynthesis, DMT1, and the mitochondrial iron handling machinery are all normal
      in hemoglobin-deficit mice, while transferrin cycling is deficient. Therefore,
      the product of Sec15l1 is directly involved in vesicular trafficking, docking,
      fusing, and/or cargo delivery in erythroid precursors.

PMID- 16647566
TI  - Isolation and characterization of human myeloid progenitor populations--TpoR as
      discriminator between common myeloid and megakaryocyte/erythroid progenitors.
AB  - OBJECTIVE: The common myeloid progenitor (CMP) and its progeny, the
      granulocyte/monocyte progenitor (GMP) and megakaryocyte/erythrocyte progenitor
      (MEP), have been isolated based on the surface expression of CD34, IL-3Ralpha,
      and CD45RA. However, high resolution of IL-3Ralpha- and IL-3Ralphalo cells
      required to adequately separate the CMP and MEP populations is difficult to
      achieve. The aim of this study was to find a complementary surface marker to
      obtain a better separation of these two populations and to further characterize
      the acquired progenitor populations. MATERIALS AND METHODS: To evaluate the
      thrombopoietin receptor (TpoR) as a candidate marker, CD19-/CD34+/IL-3Ralphalo/
      /CD45RA-/TpoR- (CMP), CD19-/CD34+/IL-3Ralphalo/CD45RA+/TpoR- (GMP), and CD19
      /CD34+/IL-3Ralphalo/-/CD45RA-/TpoR+ (MEP) cells from human bone marrow were
      sorted to semisolid cultures for colony assays, and in addition analyzed for
      their surface expression of other growth factor receptors (GFRs) and sorted to
      real-time RT-PCR for gene expression analysis. RESULTS: The colony-formation and
      gene expression assays showed that inclusion of TpoR as a marker gave a distinct
      and reproducible separation of the myeloid progenitors. Furthermore, most GFR
      surface expression correlated to gene expression, but there were also striking
      discrepancies, in particular for the common beta-chain of the IL-3R, GM-CSFR, and
      IL-5R and for TpoR. CONCLUSION: Our data establish the TpoR as an important tool
      for isolation of the myeloid progenitors and demonstrate that the surface
      expression of GFRs cannot be predicted by their gene expression. Importantly, the
      refined isolation of CMPs will allow more detailed studies of regulatory
      mechanisms steering CMPs towards erythropoiesis vs granulopoiesis in steady state
      and response to peripheral demands.

PMID- 16647567
TI  - Leukemia-stimulated bone marrow endothelium promotes leukemia cell survival.
AB  - Extensive endothelial cell proliferation and marked neovascularization are the
      most pronounced microenvironmental changes consistently observed in the bone
      marrow (BM) of patients with acute lymphoblastic leukemia (ALL). It is not known
      whether ALL cells induce this phenotype and whether they receive critical signals
      from the tumor-associated BM endothelium. Here, we show that leukemia cells
      actively stimulate BM endothelium, promote de novo angiogenesis, and induce
      neovascularization in the leukemic BM. Soluble factors, present in the leukemic
      BM microenvironment, promote the proliferation, migration, and morphogenesis of
      BM endothelial cells, which are critical processes in tumor angiogenesis. We also
      show in vitro that leukemia cells display directional motion towards assembled BM
      endothelium and following adherence exhibit cell polarization, pseudopodia, and
      ultrastructural features that suggest the existence of leukemia-endothelium cross
      talk. Finally, we show that BM endothelium promotes leukemia cell survival
      through a mechanism mediated through the anti-apoptotic molecule bcl-2. These
      studies indicate that ALL cells actively recruit BM endothelium and mediate the
      leukemia-associated neovascularization observed in ALL. Therefore, disruption of
      interactions between leukemia cells and BM endothelium may constitute a valid
      therapeutic strategy.

PMID- 16647568
TI  - Selective expression of cholesterol metabolism genes in normal CD34+CD38- cells
      with a heterogeneous expression pattern in AML cells.
AB  - OBJECTIVE: To identify adenosine triphosphate-binding-cassette (ABC) transporters
      that are selectively expressed in normal and/or leukemic CD34+CD38- stem cells.
      METHODS: Microarray experiments on murine stem cells identified 13 ABC
      transporters with a high expression level. Corresponding human transporters were
      analyzed in normal CD34+CD38- and CD34+CD38+ bone marrow cells by quantitative
      reverse transcriptase polymerase chain reaction. RESULTS: Five ABC transporters,
      including ABCG1, were differentially expressed with a higher expression in
      CD34+CD38- cells. Besides ABCG1, known to be involved in cholesterol metabolism,
      expression of another major cholesterol transporter (ABCA1), some cholesterol
      metabolism genes (3-hydroxy-3-methyl-glutaryl-CoA reductase, low-density
      lipoprotein receptor), and the transcription factor controlling ABCA1 and ABCG1
      expression, liver-X-receptor-alpha (LXR-alpha), were assessed. All these genes
      were predominantly expressed in the more primitive subpopulation, indicating a
      high rate of cholesterol metabolism and transport. Conversely in acute myeloid
      leukemia (AML), a heterogeneous expression pattern was found consisting of a
      considerably higher expression of particularly LXR-alpha in CD34+ cells and a
      reverse expression pattern in a subset of AML CD34+CD38+ cells. CONCLUSION: These
      data suggest an active cholesterol metabolism and efflux in normal CD34+CD38-
      cells, although a subgroup of AMLs potentially demonstrate a hyperactive
      cholesterol metabolism.

PMID- 16647569
TI  - Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in
      acute myeloid leukemia.
AB  - OBJECTIVE: Chemoresistance remains a major clinical obstacle to curative
      chemotherapy of acute myeloid leukemia (AML), but the molecular mechanisms
      underlying resistance to chemotherapeutic agents used in AML are largely unknown.
      We have attempted to investigate genetic mechanisms causing resistance to Ara-C
      [1-beta-D-arabinofuranosyl-cytosine (cytarabine)], one mainstay in AML
      chemotherapy for decades. MATERIAL AND METHODS: Highly Ara-C-resistant murine BXH
      2 strain AML cell lines were generated, and their molecular changes were compared
      to their sensitive parental lines. The causative changes were confirmed using a
      genetic approach. RESULTS: We derived nine highly Ara-C-resistant murine BXH-2
      strain AML sublines via in vitro selection. p21Cip1 was dramatically
      downregulated and p53 protein accumulation induced by Ara-C treatment was
      impaired in one resistant line. In this line, repeated Ara-C exposure had
      selected for cells that harbor a genomic deletion affecting the splicing of Trp53
      mRNA. This deletion produces an aberrant Trp53 mRNA, in which exon 4 is skipped,
      producing a protein lacking parts of both the transactivation and DNA-binding
      domains. Retroviral transduction of the sensitive parental cells with a dominant
      negative Trp53 cDNA caused changes in the protein levels of p21Cip1, BAX, and
      cleaved caspase-3, but not bcl-XL, and rendered the cells more resistant to Ara
      C. Unexpectedly, we found that pifithrin-alpha (PFTalpha), a compound that has
      been proposed to regulate p53 protein activity, induced apoptosis in both Ara-C
      sensitive and -resistant lines, and decreased Ara-C resistance in cells with
      either normal or mutant Trp53 genes. CONCLUSIONS: These data indicate that Trp53
      loss-of-function could partly explain the acquisition of AML chemoresistance, and
      suggest that PFTalpha could be useful in treatment of relapsed AML.

PMID- 16647570
TI  - Human herpesvirus 6 impairs differentiation of monocytes to dendritic cells.
AB  - OBJECTIVE: Monocyte-derived dendritic cells (DCs) play important roles in the
      immune response against infections and malignancies. Human herpesvirus 6 (HHV-6)
      infects monocytes and is reactivated in immunodeficient patients. To clarify the
      mechanisms of HHV-6-induced immunodeficiency, we investigated the effect of HHV-6
      infection on differentiation of monocytes to DCs. METHODS: Monocytes were
      inoculated with or without HHV-6 and then allowed to differentiate to myeloid DCs
      in culture medium containing granulocyte-macrophage colony-stimulating factor and
      interleukin (IL)-4. The expression of cell surface molecules on DCs and the
      capacity of the DCs for antigen capture were examined by flow cytometric
      analysis. Alteration of antigen-presenting capacity induced by HHV-6 infection
      was examined. RESULTS: The morphology of HHV-6-infected monocyte-derived DCs was
      distinctly different from that of the DCs derived from mock-infected monocytes.
      Although expression levels of DC-associated surface antigens, including CD80,
      CD83, and CD86, were significantly higher on HHV-6-infected monocyte-derived DCs
      than on DCs derived from mock-infected monocytes, antigen-presenting capacity was
      significantly lower in the former group. Addition of culture supernatant of HHV-6
      infected monocytes resulted in suppression of the T-lymphocyte proliferative
      response, and anti-IL-10 neutralizing antibody partly inhibited this suppressive
      effect. The antigen-presenting capacity of DCs generated from a patient with
      severe HHV-6 reactivation was significantly lower than that of DCs generated from
      the same patient in the recovery phase. CONCLUSIONS: HHV-6 infection induces
      immunodeficiency via impaired differentiation of DCs. These results present a new
      concept for the pathogenesis of HHV-6-induced immunodeficiency.

PMID- 16647571
TI  - Differentiation of murine committed megakaryocytic progenitors isolated by a
      novel strategy reveals the complexity of GATA and Ets factor involvement in
      megakaryocytopoiesis and an unexpected potential role for GATA-6.
AB  - OBJECTIVE: The differentiation of megakaryocytes is characterized by
      polyploidization and cytoplasmic maturation leading to platelet production.
      Studying these processes is hindered by the paucity of bone marrow megakaryocytes
      and their precursors. We describe a method for the expansion and purification of
      committed megakaryocyte progenitors and demonstrate their usefulness by studying
      changes in the expression of Ets and GATA family transcription factors throughout
      megakaryocytopoiesis. METHODS: A two-step serum-free method was developed. Cells
      isolated using this method were analyzed for surface marker expression by flow
      cytometry, and for their ability to differentiate using single-cell culture.
      Purified progenitors were induced to differentiate and analyzed with respect to
      their ploidy by flow cytometry and expression of specific genes by RT-PCR.
      RESULTS: A population of Lin- c-kit+ CD45+ CD41+ CD31+ CD34low CD9low
      FcgammaRII/IIIlow Sca-1med/low committed megakaryocyte progenitors was purified.
      These cells could be differentiated efficiently, achieving ploidy of up to 128N.
      Analysis of RNA demonstrated the expected increases in expression of key
      megakaryocyte-associated genes. RT-PCR analysis also revealed that a range of Ets
      and GATA factors are expressed, their individual levels and patterns of
      expression varying widely. Surprisingly, we find that GATA-6 is specifically
      expressed in late differentiated megakaryocytes and has the potential to regulate
      megakaryocyte-expressed genes in cooperation with Ets factors. CONCLUSION:
      Purified primary megakaryocytic progenitors are able to differentiate as a cohort
      into fully mature megakaryocytes. The number of cells obtainable, and the
      synchrony of the differentiation process, facilitates analysis of the dynamics of
      molecular processes involved in megakaryocytopoiesis. The expression pattern of
      Ets and GATA family transcription factors reveals the complexity of the
      involvement of these key megakaryocytic regulators. The finding of GATA-6
      expression and demonstration of its functional activity suggests a novel
      mechanism for the regulation of certain genes late in megakaryocytopoiesis.

PMID- 16647572
TI  - Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia.
AB  - OBJECTIVE: Abnormal telomere shortening has been observed in a subset of
      individuals with aplastic anemia (AA). We hypothesized that genetic variation in
      two genes critical in telomere biology, TERF1 and TERF2, could be a risk factor
      for AA. METHODS: The proximal promoter and all coding regions of TERF1 and TERF2
      were sequenced in 47 individuals with acquired AA. Regions with genetic variation
      were sequenced in an additional 95 AA patients and 289 healthy controls. Single
      nucleotide polymorphism (SNP) frequencies were analyzed using co-dominant and
      dominant models and haplotypes determined. Functional studies evaluated
      telomerase activity, telomere and telomeric overhang lengths, and TRF2 protein
      expression in select patients. RESULTS: Two nonsynonymous amino acid changes were
      detected, one in exon 9 of TERF1 and another in exon 6 of TERF2. These sequence
      variants resulted in conservative amino acid changes and were not predicted to
      alter TRF1 or TRF2 protein expression or function. SNP and haplotype analyses in
      acquired AA patients suggested that one variant allele, in intron 9 of TERF1, and
      haplotype could be associated with increased risk for aplastic anemia (OR 1.59,
      95% confidence interval 1.06-2.39, p = 0.033). TERF2 SNPs and haplotypes were not
      significantly associated with aplastic anemia. CONCLUSIONS: It is possible that a
      common genetic variant in TERF1 is associated with risk for AA but additional
      studies are required. Highly penetrant, non-synonymous, or insertion-deletion
      mutations in TERF1 and TERF2 were not identified and therefore are not likely to
      be major genetic risk factors for the development of AA.

PMID- 16647573
TI  - Bone marrow-derived keratinocytes are not detected in normal skin and only rarely
      detected in wounded skin in two different murine models.
AB  - OBJECTIVE: Because the ability of bone marrow-derived cells (BMDCs) to repopulate
      tissues and the possible mechanisms of repopulation remain controversial, we used
      two distinct murine models to determine whether BMDCs can repopulate epidermal
      keratinocytes during either steady-state homeostasis or after tissue injury.
      METHODS: The accessibility of skin keratinocytes makes it an excellent tissue to
      assess BMDC repopulation. In the two murine models, BMDCs from either male
      homologous B6, 129S Rosa26 mice that constitutively express ss-galactosidase or
      male hemizygote C57 BL/6-Tg(ACTbEGFP)1Osb/J mice expressing enhanced green
      fluorescent protein were transplanted via tail vein injection into control
      lethally irradiated (9.5 Gy) congenic female recipients and the percentage of
      keratinocytes derived from the transplanted BMDCs, both with and without
      wounding, was carefully determined. RESULTS: Analysis of bone marrow, thymus,
      spleen, and lymph nodes confirmed complete engraftment of donor BMDCs 6 months
      post-bone marrow transplantation. However, during steady-state homeostasis, bone
      marrow-derived keratinocytes could not be detected in the epidermis. In a skin
      wound-healing model, the epidermis contained only rare bone marrow-derived
      keratinocytes (< 0.0001%) but did contain scattered bone marrow-derived
      Langerhans cells. CONCLUSIONS: These results suggest that BMDCs do not
      significantly contribute to steady-state epidermal homeostasis and are not
      required or responsible for providing keratinocyte stem cells and keratinocyte
      repopulation following skin injury.

PMID- 16647574
TI  - Adhesion receptor expression by CD34+ cells from peripheral blood or bone marrow
      grafts: correlation with time to engraftment.
AB  - OBJECTIVE: This study was undertaken to define the pattern of cell adhesion
      receptor expression by the CD34+ progenitor cells from mobilized peripheral blood
      and bone marrow from normal and autologous donors, and to correlate the adhesion
      receptor profile with time to blood cell recovery for patients undergoing
      autologous transplant. METHODS: Blood cell recovery was determined by absolute
      neutrophil count (> 500/microL), time to last red cell transfusion, and platelet
      count (> 50,000/microL and > 100,000/microL). The analysis for expression of
      adhesion receptors alphaL (CD11a), alpha2 (CD49b), alpha3 (CD49c), alpha4
      (CD49d), alpha5 (CD49e), alpha6 (CD49f), beta1 (CD29), L-selectin (CD62L), ICAM-1
      (CD54), PECAM-1 (CD31), HCAM (CD44), and P-selectin (CD62P) was performed by two
      color flow cytometry. The Kruskal-Wallis test and Spearman's rank correlation
      were used for statistical analysis. RESULTS: Statistical analysis of adhesion
      expression by the CD34+ population for patients undergoing autologous transplant
      demonstrated that the higher percent expression of PECAM-1 correlated with longer
      time to platelet recovery (> 100,000/microL, p = 0.049). In contrast, the higher
      the percent expression of alpha6 (p = 0.013) and the increased density of
      expression of alpha2 (p = 0.035), alpha3 (p = 0.023), alpha4 (p = 0.044), beta1
      (p = 0.027), and ICAM-1 (p = 0.010) correlated with shorter time to platelet
      recovery. Neutrophil recovery time decreased with increased density of expression
      of alphaL (p = 0.014) and P-selectin (p = 0.007) receptors. Increased density of
      expression of CD44 (HCAM) was associated with longer time to red blood cell
      recovery (p = 0.05). CONCLUSION: These data suggest that upregulation of specific
      adhesion receptors or selection of certain cell populations could result in
      earlier blood cell recovery after transplant.

PMID- 16647575
TI  - Kinetics of plasma-cell chimerism after allogeneic stem cell transplantation by
      highly sensitive real-time PCR based on sequence polymorphism and its value to
      quantify minimal residual disease in patients with multiple myeloma.
AB  - OBJECTIVE: To investigate lineage-specific chimerism of plasma cells after
      allogeneic transplantation by real-time PCR based on bi-allelic sequence
      polymorphism or, in case of female-to-male transplantation, on the detection of
      the DFFRY gene and to determine its value to quantify minimal residual disease in
      myeloma patients. METHODS: Forty-eight samples from bone marrow samples and
      peripheral blood from 34 nonmyeloma patients were analyzed at different times
      after transplantation. Sixty-two samples from 22 myeloma patients were analyzed
      at different times after allogeneic stem cell transplantation, and results were
      compared with immunofixation and, in some cases, with PCR data using patient
      specific primers. RESULTS: The median chimerism for T cells at day +100 was
      greater than 99.9% and remained stable on day +180 and 1 year after
      transplantation. In contrast, the median donor plasma cell chimerism at day +100
      was 95.5%, at day +180 98.6%, at day +360 99.8%, and 2 or more years after
      transplantation greater than 99.9%. Sensitivity of real-time PCR using human
      short insertion/deletion polymorphisms (SIDP) was 10(-4) and in case of Y-PCR 10(
      5). Sequential monitoring of donor plasma cell chimerism showed that increasing
      and stable chimerism were associated with ongoing remission in 15 out of 16
      samples (93%), and decreases in chimerism predicted relapse in 5 out of 6
      patients. CONCLUSION: We conclude that plasma cell chimerism after allogeneic
      stem cell transplantation is delayed in comparison to T-cell chimerism.
      Sequential quantitative measurement of plasma cells after allogeneic stem cell
      transplantation with highly sensitive real-time PCR allows monitoring of residual
      host-tumor cells in patients with multiple myeloma and allows guiding adoptive
      immunotherapy strategies to enhance remission status and to prevent clinical
      relapse.

PMID- 16647576
TI  - The interplay between the pineal complex and the habenular nuclei in lower
      vertebrates in the context of the evolution of cerebral asymmetry.
AB  - This paper presents an overview on the epithalamus of vertebrates, with
      particular reference to the pineal and to the asymmetrical organization of the
      habenular nuclei in lower vertebrates. The relationship between the pineal and
      the habenulae in the course of phylogenesis is here emphasized, taking data in
      the frog as example. Altogether the data support the hypothesis, put forward also
      in earlier studies, of a correlation of habenular asymmetry in lower vertebrates
      with phylogenetic modification of the pineal complex. The present re-visitation
      was also stimulated by recent data on the asymmetrical expression of Nodal genes,
      which involves the pineal and habenular structures in zebrafish. The comparative
      analysis of data, from cyclostomes to mammals, suggests that transformation of
      epithalamic structures may play an important role in brain evolution. In
      addition, in mammals, including rodents, a remarkable complexity has evolved in
      the organization of the habenulae and their functional interactions with the
      pineal gland. The evolution of these two epithalamic structures seems to open
      also new perspectives of knowledge on their implication in the regulation of
      biological rhythms.

PMID- 16647577
TI  - Subcortical motor plasticity in patients with sporadic ALS: An fMRI study.
AB  - OBJECTIVE: To address the potential contribution of subcortical brain regions in
      the functional reorganization of the motor system in patients with sporadic ALS
      (sALS) and to investigate whether functional changes in brain activity are
      different in sALS patients with predominant upper motor neuron (UMN) or lower
      motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13
      healthy controls, using BOLD-fMRI, while they performed a simple visually paced
      motor task. Seven patients had definite clinical UMN signs while nine patients
      had prevalent clinical and electrophysiological LMN involvement. fMRI data were
      analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were
      identified in motor cortical regions in both patients and healthy controls.
      Direct group comparisons revealed relatively decreased BOLD fMRI responses in
      left sensorimotor cortex, lateral premotor area, supplementary motor area and
      right posterior parietal cortex (p < 0.05 corrected) and relatively increased
      responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients.
      Additional analyses between the two patients subgroups demonstrated significant
      BOLD fMRI response differences in the anterior cingulate cortex and right caudate
      nucleus (p < 0.001 uncorrected) with more robust activation of these areas in
      patients with greater UMN burden. Importantly, there were no significant
      differences in performance of the motor task between sALS patients and controls
      as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a
      different BOLD fMRI pattern between our sALS patients and healthy controls even
      during simple motor behavior. Furthermore, patients with sALS and greater UMN
      involvement show a different reorganization of the motor system compared to sALS
      patients with greater LMN dysfunction.

PMID- 16647578
TI  - Crayfish mechanoreceptor neuron prevents photoinduced apoptosis of satellite
      glial cells.
AB  - Interactions between neurons and glia play a key role in the development,
      functioning and survival of the nervous system. However, the influence of neurons
      on glial cells has received less attention than the role of glia in supporting
      neural functions. We here investigated the role of isolated crayfish stretch
      receptor neuron in the death of satellite glial cells under photodynamic impact.
      After staining with aluminum phthalocyanine photosens, the neuronal cell body was
      locally irradiated with a focused beam of He-Ne (633 nm, 200 W/cm2) or
      semiconductor laser (650 nm, 50 W/cm2). This rapidly abolished neuronal activity.
      The whole preparation was then subjected to total laser irradiation with lower
      intensity (633 nm, 0.3 W/cm2), which induced death of glial cells. Double
      staining of the preparation with propidium iodide and Hoechst 33342 in the
      following 6-7h allowed the visualization of necrotic, apoptotic and alive cells.
      Previous neuron inactivation with the focused laser beam was found to increase
      photodynamically-induced apoptosis but not necrosis of satellite glial cells
      enwrapping the axon. Therefore, the intact neuronal cell body protected satellite
      glial cells against photoinduced apoptosis. Altogether the data indicate that
      mechanoreceptor neurons release some signaling molecules involved in the
      prevention of glial apoptosis. This may provide integrity of the stretch receptor
      organ and its resistance to injurious factors.

PMID- 16647579
TI  - Consolidation effect of repeated processing of declarative knowledge in mental
      experiences during human sleep.
AB  - Sleep may positively influence declarative memory through the processing, which
      transforms items of declarative knowledge into contents of mental sleep
      experience (MSE). A prediction from this general hypothesis is that the
      consolidation level should be higher for the output of items repeatedly processed
      and transformed into identical or very similar (so-called interrelated) contents
      of distinct MSEs of the same night rather than for the output of items presumably
      processed once (that is, all other, non-interrelated contents). Two experiments
      examined whether and how far the frequency and long-term retention of
      interrelated contents depend on the repeated processing of given items rather
      than on the experimental procedure applied for detection of interrelated
      contents. This procedure entails both multiple awakenings and a verbal report of
      MSE after awakening. Multiple awakenings could facilitate the re-access and
      elaboration of some contents into the subsequent (i.e. contiguous) MSE rather
      than non-contiguous MSEs; verbal reports could enhance the delayed recall of
      interrelated contents in as much as repeatedly encoded. The first experiment
      showed that interrelated contents were more frequent and better retained than
      both non-interrelated and pseudo-interrelated (i.e. by-chance similar or
      identical) contents, and even more in pairs of contiguous than non-contiguous
      MSEs collected from the first four periods of REM sleep on each experimental
      night. The second experiment showed that the frequency and retention rate of
      interrelated contents, while higher than those of non-interrelated and pseudo
      interrelated contents, were not significantly different in pairs of MSEs which
      were verbally or mentally recalled after awakening provoked during the first four
      periods of REM sleep in each experimental night. Taken together, these findings
      indicate that the advantage provided by repeated processing during REM sleep for
      the consolidation of the output of items of declarative knowledge is conspicuous
      and largely independent from the experimental procedure, as this only slightly
      enhances the frequency and retention rate of interrelated contents.

PMID- 16647580
TI  - Bradykinesia in patients with Parkinson's disease having levodopa-induced
      dyskinesias.
AB  - We investigated the likelihood that bradykinesia coexisted with levodopa-induced
      dyskinesias (LID) in 10 dyskinetic Parkinson's disease patients (DPD). Their
      motor performance was compared to that of 10 age/gender-matched non-dyskinetic
      patients (NDPD) and 10 healthy controls. Whole-body movement (WBM) and rapid
      alternating movements (RAM) at the wrist were recorded simultaneously using 6
      degree of freedom magnetic motion tracker and forearm rotational sensors,
      respectively. WBM was recorded prior to, and while subjects performed pronation
      supination movements of their dominant hand with maximal rotational excursion,
      and as fast as possible for 10s. RANGE, VELOCITY and IRREGULARITY of pronation
      supination cycles were quantified to assess motor performance. Results show that
      DPD patients had greater WBM than NDPD and controls during rest and RAM
      performance, as expected. There were no differences in motor performance between
      DPD and NDPD groups for RANGE and VELOCITY, despite significantly longer disease
      duration for the DPD group (15.5+/-6.2 years versus 6.6+/-2.6 years). However,
      both the NDPD and DPD groups showed significantly lower RANGE and reduced
      VELOCITY compared to controls, suggesting the presence of bradykinesia. For
      IRREGULARITY, DPD patients showed increased fluctuations in pronation-supination
      cycle amplitude compared to NDPD and controls. However, the lack of correlation
      between WBM magnitude and IRREGULARITY within the DPD group (Spearman's rank
      order, rho = 0.31, p > 0.05), suggests that LID were not the primary cause of
      increased IRREGULARITY. In conclusion, our results demonstrated that bradykinesia
      can coexist with dyskinesias, suggestive of distinct neural circuits. Our results
      also demonstrated that the occurrence of LID is not inevitably accompanied with
      worsening of motor performance.

PMID- 16647581
TI  - Calbindin-D28k and calretinin immunoreactivity in the spinal cord of the lizard
      Gekko gecko: Colocalization with choline acetyltransferase and nitric oxide
      synthase.
AB  - The distribution of the calcium-binding proteins calbindin-D28k (CB) and
      calretinin (CR) was investigated in the spinal cord of the lizard Gekko gecko, by
      means of immunohistochemical techniques. Abundant cell bodies and fibers
      immunoreactive for either CB or CR were widely distributed throughout the spinal
      cord. Most neurons and fibers were labeled in the superficial dorsal horn, but
      numerous cells were also located in the intermediate gray and ventral horn.
      Distinct CB- and CR-containing cell populations were observed, although double
      immunohistochemistry revealed that 17-20% of the single-labeled cells for CB or
      CR in the dorsal horn contained both proteins. In addition, nitric oxide synthase
      was immunodetected in about 6% of the CB-positive neurons in the dorsal horn and
      in 10% in the ventral horn, whereas nitric oxide synthase was present in 9-13% of
      CR-positive cells in the dorsal horn and in 14% in the ventral horn. These doubly
      immunoreactive cells were restricted to areas IV, VII and VIII. Similar
      colocalization experiments revealed that 18-24% of the cholinergic cells in the
      ventral horn contained CB and 21-30% CR, with some variations throughout the
      length of the spinal cord. The pattern of distribution for CB and CR
      immunoreactivity in the spinal cord of the lizard, reported in the present study,
      is largely comparable to those reported for mammals, birds and anuran amphibians
      suggesting a high degree of conservation of the spinal systems modulated by these
      calcium-binding proteins.

PMID- 16647582
TI  - Pro-epileptic effect of alfentanil in rats subjected to pilocarpine-induced
      chronic epilepsy.
AB  - Pharmacological induction of epileptiform activity is a complementary method to
      study the epileptogenic area in drug-resistant epileptic patients. Among the
      different activation methods, fentanyl derivatives (e.g. alfentanil) provide one
      of the most efficient tools in triggering epileptiform abnormalities in surgical
      candidates. In this study, we tested the pro-epileptic effect of different
      concentrations of alfentanil in hippocampal slices obtained from control and
      pilocarpine-treated chronic epileptic rats. The pro-convulsant action of
      alfentanil was also studied in control and pilocarpine-treated epileptic rats
      implanted with subdural and hippocampal electrodes for electroencephalographic
      recordings. In 90% of slices from control animals, application of alfentanil (0.1
      5 microM) induced a significant enhancement in amplitude and number of population
      spikes recorded in the hippocampal CA1 region. In contrast, alfentanil produced a
      significant reduction in the amplitude of population spikes in slices from
      pilocarpine-treated epileptic rats. These changes were accompanied by a
      significant increase in the number of population spikes in the form of
      epileptiform multispike responses of epileptic slices. Naloxone (20 microM)
      antagonized the effect of alfentanil in both control and epileptic slices,
      reducing the number of population spikes in slices from epileptic rats. In
      control rats, alfentanil induced epileptiform abnormalities in the hippocampal
      and cortical electroencephalographic recordings but only at concentrations higher
      than 200 microg/kg (e.g. 350 microg/kg). Lower doses of alfentanil (25 microg/kg)
      elicited epileptiform abnormalities only in chronic epileptic rats. The potent
      action of a minimal dose of alfentanil in inducing epileptiform activity suggests
      an enhancement of the pro-convulsant action of mu-receptor opioids in chronic
      temporal lobe epilepsy.

PMID- 16647583
TI  - Localization of neuregulin-1alpha (heregulin-alpha) and one of its receptors,
      ErbB-4 tyrosine kinase, in developing and adult human brain.
AB  - Using immunohistochemistry, Western blot analysis, and RT-polymerase chain
      reaction, we studied the distribution of neuregulin-1 splice variant alpha (NRG
      1alpha) and one of its putative receptors, ErbB-4 tyrosine kinase, in human
      brain. In the pre- and perinatal human brain immunoreactivity was confined to
      numerous neurons, with the highest cell density found in cortical gray matter,
      hypothalamus and cerebellum. In the adult brain, single cortical gray and white
      matter neurons showed NRG-1alpha immunoreactivity. Occasionally, immunoreactive
      oligodendrocytes were observed. NRG-1alpha-expressing neurons were also found in
      the hypothalamus, hippocampus, basal ganglia and brain stem. Application of two
      antibodies recognizing alpha and beta isoforms revealed a different distribution
      pattern in that many cortical and hippocampal pyramidal neurons were labeled.
      ErbB-4 immunoreactivity was expressed in both neurons and oligodendrocytes. Our
      data show that NRG-1alpha expression is lower in the adult human brain than in
      the developing brain, and, therefore, support a role for NRG-1alpha in brain
      development.

PMID- 16647584
TI  - Repeated acute exposures to hypergravity during early development subtly affect
      CD-1 mouse neurobehavioural profile.
AB  - Exposure to altered gravitational environment, especially during critical
      ontogenetic phases, may induce persistent nervous system modifications and
      behavioural anomalies. This study evaluated the effects of hypergravity exposure
      on the development of the nervous system and assessed the relevance of parity in
      the mother's responses to altered gravitational stimuli. CD-1 mouse pups of both
      sexes delivered by primiparous and biparous dams were exposed to 1h of 2 G
      rotationally induced hypergravity from PND2 to PND9. Sensorimotor responses and
      somatic growth were daily measured (PND2-PND15), ultrasonic vocalisations
      recorded on PNDs 2, 5 and 9, and homing behaviour evaluated on PND12. In
      addition, spatial orientation ability was assessed in a T-maze on PND18, while
      mice exploratory behaviour and locomotor activity were evaluated in an open-field
      test (PND21). Long-term effects of hypergravity exposure on both spatial learning
      (Morris water-maze test) and brain levels of NGF and BDNF were also investigated
      at adulthood. Rotation per se induced a delay in somatic growth, sensorimotor
      responses and ultrasonic vocalisation profile, while hypergravity highlighted sex
      differences in open-field behaviour. Strategies to solve a spatial learning task,
      rather than learning per se, were affected by early exposure to rotation, while
      hypergravity selectively altered behavioural profile in the reversal phase of the
      test. Early exposure to rotation per se also decreased hypothalamic BDNF levels,
      while hypergravity reduced NGF levels in the frontal cortex. Previous maternal
      experience did not interact with hypergravity exposure, while differences between
      offspring of primiparous and biparous dams were observed in sensorimotor
      development and exploratory behaviour.

PMID- 16647585
TI  - Intranasal administration of IGF-I improves behavior and Purkinje cell pathology
      in SCA1 mice.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the
      expansion of polyglutamine repeat within ataxin-1 protein. Cerebellar Purkinje
      cells are the primary targets of SCA1 pathology. These cells synthesize insulin
      like growth factor-I (IGF-I) and express its receptors during their entire life.
      The aim of present study was to determine if intranasally administered IGF-I to
      SCA1 transgenic mice suppresses toxic effects of ataxin-1. Two-week old SCA1
      heterozygous animals were randomly divided into two treatment groups of IGF-I (30
      and 60 microg IGF-I/animal) and a vehicle-treated control group. The wildtype
      animals served as normal controls. IGF-I or vehicle was administered at 48 h
      intervals for the total of 10 doses. Animals were then subjected to rotarod test,
      sacrificed, brains removed and processed for immunohistochemical and Western blot
      analysis. Radiolabeled IGF-I and bioactive TAT peptide accumulated in the brains
      of SCA1 mice following intranasal administration validating the use of intranasal
      route. SCA1 mice showed SCA1 pathology with impaired motor function and
      downregulation of calcium binding proteins as compared to wildtype mice. However,
      30 and 60 microg IGF-I-treated animals showed improved performance on the rotarod
      as compared to vehicle-treated SCA1 mice with significant improvement (p < 0.05)
      on day 3 in 60 microg IGF-I group. The immunohistochemical data further showed
      partial recovery in the expression of calbindin D28k and protein kinase C-gamma
      in Purkinje cells in IGF-I-treated SCA1 animals. Our results indicate that
      suppression of ataxin-1-mediated adverse effects by intranasal IGF-I treatment
      may be of a therapeutic value to treat SCA1.

PMID- 16647586
TI  - Mild prenatal protein malnutrition increases alpha 2C-adrenoceptor expression in
      the rat cerebral cortex during postnatal life.
AB  - Mild reduction in the protein content in the diet of pregnant rats from 25 to 8%
      casein, calorically compensated by carbohydrates, does not alter body and brain
      weights of rat pups at birth, but results in significant changes of the
      concentration and release of cortical noradrenaline during postnatal life,
      together with impaired long-term potentiation and memory formation. Since some
      central noradrenergic receptors are critically involved in neuroplasticity, the
      present study evaluated, by utilizing immunohistochemical methods, the effect of
      mild prenatal protein malnutrition on the alpha 2C-adrenoceptor expression in the
      frontal and occipital cortices of 8- and 60-day-old rats. At day 8 of postnatal
      age, prenatally malnourished rats exhibited a three-fold increase of alpha 2C
      adrenoceptor expression in both the frontal and the occipital cortices, as
      compared to well-nourished controls. At 60 days of age, prenatally malnourished
      rats showed normal expression levels scores of alpha 2C-adrenoceptor in the
      neocortex. Results suggest that overexpression of neocortical alpha 2C
      adrenoceptors during early postnatal life, subsequent to mild prenatal protein
      malnutrition, could in part be responsible for neural and behavioral disturbances
      showing prenatally malnourished animals during the postnatal life.

PMID- 16647587
TI  - Antioxidant response analysis in the brain after pilocarpine treatments.
AB  - Cholinergic and gabaergic systems play an important role generating
      electroencephalographic activity and regulating vigilance states. Pilocarpine is
      a cholinergic agonist commonly used to induce seizures and an epilepticus-like
      state in rodents. A relationship between status epilepticus and reactive oxygen
      species has been also suggested which could result in seizure-induced
      neurodegeneration. The aim of this study was to evaluate the existence of
      oxidative damage as well as the antioxidant enzyme response in cortex and
      hippocampus after the administration of an intraperitoneal (350 mg/kg) and an
      intracerebroventricular (360 microg, 1 microl) pilocarpine injection in rats. The
      GABA agonist muscimol (1 mg/kg, i.p.), with described neuroprotective properties,
      was used as a negative control. Only systemic pilocarpine induced oxidative
      damage. Malondialdehyde levels, as a marker of lipid peroxidation (LP), increased
      in both regions (55-56%). Catalase (52-80%) and superoxide dismutase (53-60%)
      activities also rose in both regions but glutathione peroxidase activity only
      increased in cortex (45%). Glutathione reductase and caspase-3 activity did not
      change. In conclusion, systemic pilocarpine produced oxidative brain damage,
      whereas local pilocarpine brain injection had no effects. Moreover, the enzymatic
      determinations performed in this study are a good tool to study brain injury in
      pharmacological manipulations such as the ones used in short recording EEG
      studies.

PMID- 16647588
TI  - Pentobarbital inhibits L-DOPA-induced dopamine increases in the rat striatum: An
      in vivo microdialysis study.
AB  - Pentobarbital is reported to inhibit ketamine-induced dopamine (DA) release in
      the rat nucleus accumbens. The accumbens is a part of the limbic dopaminergic
      system in the brain, and the dopaminergic neural activity of other components may
      also be sensitive to pentobarbital. We investigated the effect of pentobarbital
      administration on DA release in the striatum known as DA-rich basal ganglia, and
      the interaction between pentobarbital and L-DOPA, using in vivo microdialysis
      techniques. Male SD rats were implanted microdialysis probe into the right
      striatum. The probe was perfused with modified Ringer's solution and dialysate
      was directly injected to an HPLC. Every group of rats was consisted of six to
      seven animals. In the first experiment, rats were given saline, 25 and 50 mg kg(
      1) pentobarbital. The second, each rat was given a local administration of 2 and
      5 microg ml(-1) of L-DOPA with perfusate. Finally, other sets of rats were given
      5 microg ml(-1) of L-DOPA and 25, 50, or 100 mg kg(-1) pentobarbital.
      Pentobarbital anaesthesia decreased the extracellular concentration of DA, and
      local administration of L-DOPA significantly increased DA concentration.
      Pretreatment with pentobarbital diminished the L-DOPA-induced DA increase. The
      results of the present investigation demonstrate that administration of
      pentobarbital might inhibit dopaminergic neural activity not only in the nucleus
      accumbens but also in the rat striatum. Pentobarbital anaesthesia antagonizes DA
      increase induced by L-DOPA and suggests the inhibition of metabolism of L-DOPA.
      The results of some animal experiments on dopaminergic activity under
      pentobarbital anaesthesia should be reconsidered.

PMID- 16647589
TI  - When does chronic pain become intractable and when is pharmacological management
      no longer appropriate? The pain specialist's perspective.

PMID- 16647590
TI  - Spinal cord stimulation in complex regional pain syndrome and refractory
      neuropathic back and leg pain/failed back surgery syndrome: results of a
      systematic review and meta-analysis.
AB  - The drive for good quality evidence has highlighted the importance of well
      conducted systematic reviews and meta-analyses that critically evaluate and grade
      studies for new or existing therapies. A systematic review and meta-analysis was
      performed to review the efficacy, safety, and cost effectiveness of spinal cord
      stimulation (SCS) in complex regional pain syndrome (CRPS) and refractory
      neuropathic back and leg pain/failed back surgery syndrome (FBSS). The results
      support the use of SCS in patients with refractory neuropathic back and leg
      pain/FBSS (Grade B evidence) and CRPS type I (Grade A evidence)/type II (Grade D
      evidence). SCS not only reduces pain, improves quality of life, reduces analgesic
      consumption, and allows some patients to return to work, with minimal significant
      adverse events, but may also result in significant cost savings over time.

PMID- 16647591
TI  - Complex regional pain syndrome: manifestations and the role of neurostimulation
      in its management.
AB  - The hallmark of complex regional pain syndrome (CRPS) is excruciating pain
      (aching, burning, pricking, or shooting). Diagnosis should be established as soon
      as possible, as response to treatment is adversely affected by any delay.
      Treatment of CRPS is aimed at improving function, using an interdisciplinary,
      time-dependent, patient-dependent approach that encompasses rehabilitation,
      psychological therapy, and pain management. If no response to conventional
      treatment (e.g., pharmacotherapy) is noted within 12-16 weeks, a more
      interventional technique such as spinal cord stimulation (SCS) should be used.
      SCS has been shown to be highly effective in the treatment of CRPS type I,
      resulting in a significant, long-term reduction in pain and improvement in
      quality of life. SCS is particularly effective at helping to restore function in
      affected extremities, especially if applied early in the course of the disease.
      SCS is also cost effective and improves health-related quality of life.

PMID- 16647592
TI  - Neurostimulation for chronic neuropathic back pain in failed back surgery
      syndrome.
AB  - Failed back surgery syndrome (FBSS) is defined as persistent or recurrent pain,
      mainly in the lower back and/or legs, even after previous anatomically successful
      spinal surgery. Treatment of such patients is difficult, with conservative
      therapy and repeated back surgery often proving unsuccessful at providing
      adequate pain relief. Spinal cord stimulation (SCS) is a minimally invasive
      procedure that allows physicians and patients to inexpensively evaluate the
      response to therapy before permanent implantation. Both trial stimulation and
      permanent implantation are fully reversible. Early treatment with SCS has been
      shown to be very effective in well-selected FBSS patients and should be
      considered instead of reoperation. Clinical studies have demonstrated that SCS
      provides a sustained, long-term, 50% or more reduction in pain in over 60% of
      patients and allows concomitant pain medication to be reduced. The substantial
      improvements in quality of life and functional status permit many patients to
      return to work. Patients express great satisfaction with SCS and minimal side
      effects are observed. Moreover, SCS has been shown to be a cost-effective
      alternative to conventional therapies. Thus, SCS is the treatment of choice in
      medically refractory FBSS patients where recurrent neuropathic pain persists
      after surgery and analgesics are no longer effective or accompanied by
      intolerable side effects.

PMID- 16647593
TI  - The role of neurostimulation: the neurosurgical perspective.

PMID- 16647594
TI  - Spinal cord stimulation for critical leg ischemia: a review of effectiveness and
      optimal patient selection.
AB  - Patients suffering from inoperable critical leg ischemia (CLI) ultimately face a
      major amputation. Spinal cord stimulation (SCS) has been introduced as a possible
      treatment option. This paper presents the best available evidence from a
      systematic review on the effectiveness of SCS in these patients and discusses the
      indications for SCS therapy. A meta-analysis of six controlled trials, including
      444 patients, showed 11% (95% confidence interval: -0.02 to -0.20) lower
      amputation rate after 12 months compared to those treated with optimum medical
      treatment. In addition, SCS patients required significantly fewer analgesics and
      showed a significant clinical improvement. These positive effects have to be
      weighed against the higher costs and (generally minor) complications of SCS.
      TcpO(2) measurements were found to be useful in selecting the most respondent
      patients, yielding a 12-month limb salvage up to 83%. Hence, SCS should be
      considered as a possible treatment option in patients with CLI, particularly if
      their foot TcpO(2) is between 10 and 30 mmHg.

PMID- 16647595
TI  - Spinal cord stimulation for the management of refractory angina pectoris.
AB  - Despite sophisticated medical and surgical procedures, including percutaneous
      endovascular methods, a large number of patients suffer from chronic refractory
      angina pectoris. Improvement of pain relief in this category of patients requires
      the use of adjuvant therapies, of which spinal cord stimulation (SCS) seems to be
      the most promising. Controlled studies suggest that in patients with chronic
      refractory angina, SCS provides symptomatic relief that is equivalent to that
      provided by surgical or endovascular reperfusion procedures, but with a lower
      rate of complications and rehospitalization. Similarly, SCS proved cost effective
      compared to medical as well as surgical or endovascular approaches in a
      comparable group of patients. This technique is still met with reluctance by the
      medical community. Reasons for this disinclination may be related to incomplete
      understanding of the mechanism of action of SCS and the fact that SCS refers to
      the modulation of neuroendocrine parameters rather than to revascularization,
      which is currently the dominant treatment paradigm in coronary artery disease.

PMID- 16647596
TI  - Mode of action of spinal cord stimulation in neuropathic pain.
AB  - Spinal cord stimulation emerged as a spin-off from the classical gate-control
      theory, which, however, does not suffice to explain its clinical effects. Whether
      or not nociceptive forms of pain may be attenuated remains a controversial issue.
      Previous experimental studies aiming at elucidating the underlying mechanisms
      were performed on intact, anesthetized animals and were therefore of limited
      clinical relevance. Not until recent years have some data on the mode of action
      accumulated providing evidence that gamma-aminobutyric acid (GABA) ergic as well
      as adenosine-related mechanisms are involved in the pain amelioration. It appears
      that the effects are exerted mostly via segmental spinal levels, but recent
      evidence suggests that a supraspinal loop may also be of importance; this issue
      remains to be resolved. It should be emphasized that most experimental data
      pertaining to the mode of action are derived from so-called animal models of
      neuropathic pain. However, caution must be exercised in the translation of such
      data from bench to bedside, because some behavioral signs interpreted as "pain"
      in such models may be misleading. We still need animal studies to generate basic
      data but these findings should also be confirmed in humans.

PMID- 16647598
TI  - Teaching and evaluating surgical skills.

PMID- 16647599
TI  - Surgical education for the twenty-first century: beyond the apprentice model.
AB  - Traditionally, surgery has been taught by an apprentice model, where the learner
      imitates the actions of a skilled mentor. Although effective, this model is
      inefficient because it requires learners to be exposed to a large number of
      surgeries performed by a limited number of dedicated teaching faculty. In
      addition, competence is proved with subjective evaluations. Because of changes in
      modern medical practice, specifically reimbursement issues, resident work hour
      restrictions, and need for reliable and valid credentials, the critical
      components of the apprentice model are eroding. A paradigm shift is needed in
      modern surgical education.

PMID- 16647600
TI  - Changing the way we train gynecologic surgeons.
AB  - To ensure the integrity of gynecologic surgical practices and patient safety,
      changes need to be made in the training of gynecologic surgeons, both in
      residency and continuing surgical education. Although society demands competency
      in the training and continuing education of airline pilots, little is done in
      comparison to ensure competency in the training and continuing education of
      gynecologic surgeons. Both professions rely on safe performance to protect the
      well-being of individuals. It is now time for medical and surgical education to
      move from the shadows of its "trust me" attitude into the light of a "test me and
      prove me" criterion.

PMID- 16647601
TI  - Implementing a surgical skills training program.
AB  - Significant change is underway in surgical training programs. Many educators
      believe that an outcomes-based approach to surgical education best addresses the
      need for greater public accountability and patient safety in surgical education.
      To achieve this end, surgical educators need to understand the basic principles
      of curriculum design and demonstrate a willingness to apply these educational
      methods within their training programs.

PMID- 16647602
TI  - The objective structured assessment of technical skills and the ACGME
      competencies.
AB  - Objective structured assessment of technical skills is structured operating room
      or laboratory assessment of residents' surgical skills. It can be used to
      evaluate and teach both basic and complex skills to residents. The literature on
      its use is reviewed. Future use of virtual reality simulators is discussed.

PMID- 16647603
TI  - From the simple to the sublime: incorporating surgical models into your surgical
      curriculum.
AB  - Financial and time constraints have limited graduating residents' operative
      experience, making the use of models a necessary adjunct to a complete surgical
      curriculum. Models are useful tools to teaching surgical skills outside the
      operating room. They can be very realistic and complex, or they can be simple and
      economical. Models are developed to represent the anatomic arrangements seen in
      human patients, and to reproduce the biomechanical tasks necessary to complete a
      surgical case. Bench model laboratories are well-received by trainees and steepen
      the learning curve in the operating room.

PMID- 16647604
TI  - Simulators and virtual reality in surgical education.
AB  - This article explores the pros and cons of virtual reality simulators, their
      abilities to train and assess surgical skills, and their potential future
      applications. Computer-based virtual reality simulators and more conventional box
      trainers are compared and contrasted. The virtual reality simulator provides
      objective assessment of surgical skills and immediate feedback further to enhance
      training. With this ability to provide standardized, unbiased assessment of
      surgical skills, the virtual reality trainer has the potential to be a tool for
      selecting, instructing, certifying, and recertifying gynecologists.

PMID- 16647605
TI  - Mental practice and acquisition of motor skills: examples from sports training
      and surgical education.
AB  - Learning surgical skills involves both fine and gross motor skills, and
      necessitates performance in stressful situations. This environment is similar to
      the environment in which an athlete performs. Mental imagery has been used
      successfully in training athletes of all levels of proficiency and enhances both
      motor skills and motivational skills of performing under stress. The literature
      of using mental imagery to train surgeons is limited to the teaching of simple
      surgical skills, but shows promise as another tool to teach technical skills.

PMID- 16647606
TI  - Teaching and evaluating ultrasound skill attainment: competency-based resident
      ultrasound training for AIUM accreditation.
AB  - Modern obstetrics and gynecology practice requires the frequent use of ultrasound
      and ultrasound training as a required component of obstetrics and gynecology
      residencies. Although programs do offer training in obstetric ultrasound imaging,
      education in gynecologic imaging is either absent or limited. This article
      describes a comprehensive ultrasound curriculum for obstetrics and gynecology
      residents that has been developed and implemented at the University of New
      Mexico. The curriculum is competency based and qualifies the graduating resident
      to seek American Institute of Ultrasound in Medicine laboratory accreditation.

PMID- 16647607
TI  - How to teach and evaluate learners in the operating room.
AB  - The operating room is the universally established forum for learning surgical
      skills. It is the least structured and studied format, however, for teaching
      surgery. Establishing mutual, clear goals and expectations with residents or
      fellows before each case and reviewing their performance immediately after the
      case maximizes learning in the operating room.

PMID- 16647608
TI  - Avoiding pitfalls: lessons in surgical teaching.
AB  - Becoming a good surgical educator takes time, patience, and dedication. Providing
      effective feedback is essential to improving the mentee's surgical skills. The
      operating room is a costly, high-risk classroom. Residents must come to the
      operating room prepared. Using a surgical skills laboratory can help in that
      preparation but is only effective when feedback is given regarding performance.
      While in the operating room, the attending physician must constantly direct,
      critique, and actively teach.

PMID- 16647609
TI  - B-type natriuretic peptide and artery stiffness.

PMID- 16647610
TI  - Regression of left ventricular hypertrophy: lodestar to stroke prevention in the
      treatment of hypertension?

PMID- 16647611
TI  - B-type natriuretic peptide and arterial stiffness in healthy Japanese men.
AB  - BACKGROUND: Recent evidence suggests that even a slight increase in the plasma
      level of B-type natriuretic peptide (BNP) may be a marker of cardiovascular risk;
      however, the mechanisms underlying the association are currently unclear. Because
      increased arterial stiffness, as reflected by an increase of the pulse wave
      velocity (PWV) or pulse pressure (PP), may contribute to increasing plasma BNP
      levels, in the present study we investigated the relationships between the plasma
      BNP level and the PWV and PP, all of which are known markers of cardiovascular
      risk, in a healthy male Japanese cohort. METHODS: This was a cross-sectional
      study of 725 healthy Japanese men (age, 54 +/- 4 years). The PWV was assessed by
      the volume-rendering method. Plasma BNP levels were determined with a high
      sensitivity noncompetitive immunoradiometric assay. RESULTS: A univariate linear
      regression analysis demonstrated that the plasma BNP level was significantly
      correlated with age (r = 0.20, P < .01), PWV (r = 0.12, P < .01), and PP (r =
      0.17, P < .01). A stepwise multivariate linear regression analysis demonstrated
      that both the PWV and PP were significantly associated with the plasma BNP level,
      independent of age. CONCLUSION: In healthy Japanese men, stiffening of large
      arteries, as evidenced by an increase of the PWV or PP, may account at least in
      part for elevated plasma BNP levels, even within the so-called normal range.

PMID- 16647612
TI  - Interaction between body mass index and alcohol intake in relation to blood
      pressure in HAN and SHE Chinese.
AB  - BACKGROUND: Blood pressure (BP) increases with body mass index (BMI) and
      excessive alcohol intake. Few epidemiologic studies explored the interaction
      between BMI and alcohol intake in relation to BP. METHODS: We randomly selected
      10 villages with a mixed population of HAN and SHE Chinese in the JingNing County
      in Southeast China. We measured BP, anthropometric characteristics, and alcohol
      intake in 1688 participants. Our statistical methods included single and multiple
      linear and logistic regressions. RESULTS: HAN (n = 520) and SHE (n = 1168) had a
      similar sex and age distribution. SHE Chinese, compared with HAN, had a higher BP
      (128.0/79.7 v 121.5/76.9 mm Hg, P < .001), and more frequently reported alcohol
      intake (45.0% v 27.7%; P < .001), but showed lower BMI (22.2 v 22.5 kg/m2; P =
      .05) and waist-to-hip ratio (0.83 v 0.87; P < .001). In SHE, but not HAN, there
      was a significant interaction (P < .01) between BMI and alcohol intake in
      relation to BP. In SHE with BMI < 25 kg/m2, BP was significantly higher in
      drinkers than nondrinkers (129.4/80.2 v 124.2/77.4 mm Hg, P < .001), whereas
      among SHE with BMI > or = 25 kg/m2, BP was not associated with alcohol intake
      (134.3/84.9 v 136.8/85.7 mm Hg, P > .41). Accordingly, in SHE Chinese, the slope
      of BP associated with BMI was less steep (P < .01) in drinkers than nondrinkers.
      CONCLUSIONS: Among SHE Chinese, alcohol intake and BMI interactively influenced
      BP. Further research is required to elucidate the underlying mechanism.

PMID- 16647613
TI  - Are blood pressure predictors of cardiovascular disease mortality different for
      prehypertensives than for hypertensives?
AB  - BACKGROUND: The ability of diastolic, systolic, mean arterial, and pulse
      pressures to predict cardiovascular disease (CVD) morality has not been assessed
      for persons with prehypertension (diastolic pressure 80 to 89 mm Hg or systolic
      pressure 120 to 139 mm Hg). METHODS: Cox's regression analyses were conducted
      using 4849 subjects aged 33 to 87 years from the First National Health and
      Nutrition Examination Survey Epidemiologic Follow-up Study. A correction was made
      for the regression-dilution bias. RESULTS: There were 327 cardiovascular disease
      and 258 coronary heart-disease deaths during an average follow-up of 8.6 years.
      For nonelderly prehypertensives, systolic blood pressure (BP) was a stronger
      predictor than diastolic BP. The multivariate single predictor hazard ratios (95%
      confidence interval) for CVD mortality were 1.43 (0.65-3.14) and 2.11 (1.28
      3.49), for a 10 mm Hg increment diastolic and systolic BP, respectively. For
      elderly prehypertensives, it was reversed. The equivalent results were 1.53 (1.10
      2.13) and 1.25 (0.89-1.60), respectively. For nonelderly hypertensives, diastolic
      BP was a stronger predictor than systolic BP, and for elderly hypertensives it
      was reversed. Diastolic and systolic BP provided as much as or more predictive
      information than pulse and mean arterial pressure in all analyses. CONCLUSIONS:
      For nonelderly prehypertensives, systolic BP was the strongest predictor, whereas
      for hypertensives the strongest predictor was diastolic BP. For elderly subjects
      this pattern was reversed.

PMID- 16647614
TI  - Diverse associations of microalbuminuria with C-reactive protein, interleukin-18
      and soluble CD 40 ligand in male essential hypertensive subjects.
AB  - BACKGROUND: Microalbuminuria (MA) and low-grade inflammation constitute emerging
      markers of subclinical atherosclerosis. We investigated whether urinary albumin
      excretion, expressed as the albumin-to-creatinine ratio (ACR), is associated with
      high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, and soluble
      CD40 ligand (sCD40L), in hypertensive subjects. METHODS: The study population
      consisted of 108 nondiabetic male patients with newly diagnosed untreated stage I
      to II essential hypertension (aged 44.6 years, office blood pressure [BP] 148/95
      mm Hg). According to ACR values determined as the average of two nonconsecutive
      overnight spot urine samples, subjects were divided into microalbuminurics (n =
      28) (mean ACR = 30 to 300 mg/g) and normoalbuminurics (n = 80) (mean ACR <30
      mg/g). RESULTS: Although microalbuminurics as compared to normoalbuminuric
      hypertensives had greater hs-CRP levels (2.55 +/- 1.18 v 1.45 +/- 0.52 mg/L, P <
      .0001), independently of confounding factors, these two groups did not differ
      regarding IL-18 and sCD40L values (P = not significant [NS] for both cases). In
      the entire population, ACR exhibited a positive correlation with hs-CRP (r =
      0.623, P < .0001), whereas there was no association with both IL-18 and sCD40L (P
      = NS for both cases). When multiple linear regression analysis was performed, it
      was revealed that age, body mass index, office systolic BP, total cholesterol,
      and hs-CRP levels were significant independent predictors of the ACR (P < .05).
      CONCLUSIONS: In essential hypertensive subjects, MA is accompanied by elevated hs
      CRP levels, but not by augmented IL-18 and sCD40L concentrations, suggesting
      activation of different inflammatory pathways in the progression of renal and
      cardiovascular atherosclerotic disease. The pathophysiologic mechanisms of these
      associations remain to be further elucidated in future studies.

PMID- 16647615
TI  - Associations of microalbuminuria with inflammation markers in hypertensive men.

PMID- 16647616
TI  - A comparison of home measurement and ambulatory monitoring of blood pressure in
      the adjustment of antihypertensive treatment.
AB  - BACKGROUND: The purpose of this study was to compare home and ambulatory blood
      pressure (BP) in the adjustment of antihypertensive treatment. METHODS: After a 4
      week washout period, patients whose untreated daytime diastolic ambulatory BP
      averaged > or = 85 mm Hg were randomized to be treated according to their
      ambulatory or home BP. Antihypertensive treatment was adjusted at 6-week
      intervals according to the mean daytime ambulatory diastolic BP or the mean home
      diastolic BP, depending on the patient's randomization group. If the diastolic BP
      stayed above 80 mm Hg, the physician blinded to randomization intensified
      hypertensive treatment. RESULTS: Ninety-eight patients completed the study.
      During the 24-week follow-up period both systolic and diastolic BP decreased
      significantly within both groups (P < .001). At the end of the study, the
      systolic/diastolic differences between ambulatory (n = 46) and home (n = 52) BP
      groups in home, daytime ambulatory, night-time ambulatory, and 24-h ambulatory BP
      changes averaged 2.6/2.6 mm Hg, 0.6/1.7 mm Hg, 1.0/1.4 mm Hg, and 0.6/1.5 mm Hg,
      respectively (P range .06 to .75) A nonsignificant trend to more intensive drug
      therapy in the ambulatory BP group and a nonsignificant trend to larger share of
      patients reaching (57.7% v 43.5%, P = .16) the target pressure in the home BP
      group was observed due to the 3.8 mm Hg difference in ambulatory and home
      diastolic BP at randomization. CONCLUSIONS: The adjustment of antihypertensive
      treatment based on either ambulatory or home BP measurement led to good BP
      control. No significant between-group differences in BP changes were seen at the
      end of the study. Additional research is needed to provide more conclusive
      results.

PMID- 16647617
TI  - Ambulatory or home blood pressure monitoring for treatment adjustment?

PMID- 16647618
TI  - Increased skin capillary density in treated essential hypertensive patients.
AB  - BACKGROUND: Microvascular rarefaction is a hallmark of essential hypertension. We
      measured the skin capillary density in nondiabetic hypertensive subjects with
      effective antihypertensive treatment and evaluated possible correlations with
      arterial blood pressure (BP). METHODS: This cross-sectional observational study
      included 76 (55 +/- 1 years) consecutive outpatients with essential hypertension
      under chronic antihypertensive drug treatment (BP < 140/90 mm Hg), 24 age- and
      sex-matched patients with recently discovered and never-treated hypertension and
      70 normotensive (BP < 140/90 mm Hg) age- and sex-matched healthy controls. We
      used intravital video-microscopy to measure basal and maximal (during venous
      congestion) skin capillary densities in the dorsum of the fingers. Aortic
      stiffness was evaluated using pulse wave velocity and central aortic pressure
      calculated from radial artery applanation tonometry. RESULTS: Baseline and
      maximal capillary densities (number/mm2) were significantly lower (59.6 +/- 2.0
      and 62.0 +/- 1.9) in untreated than in treated hypertensive patients (74.0 +/-
      1.4 and 79.4 +/- 1.5; P < .001) and than in normotensives (68.2 +/- 1.5 and 72.4
      +/- 1.5; P < .001). Based on multiple regression analysis, after adjustment to
      tobacco consumption, aortic (and not brachial) systolic BP was inversely
      correlated with basal and postocclusive capillary densities in normotensive
      subjects. In hypertensives, this correlation disappears and capillary density was
      influenced by two independent variables, antihypertensive drug treatment and
      overweight. CONCLUSIONS: In nondiabetic hypertensive patients, capillary density
      is reduced in association with a cluster of cardiovascular risk factors involving
      tobacco consumption and obesity. The finding of an increased capillary density in
      effectively treated antihypertensives suggests that a cause-to-effect
      relationship between BP and capillary density should be evaluated in a long-term
      prospective follow-up.

PMID- 16647619
TI  - Microvascular rarefaction in hypertension--reversal or over-correction by
      treatment?

PMID- 16647620
TI  - Ambulatory blood pressure and family history of hypertension in healthy men and
      women.
AB  - BACKGROUND: Family history of hypertension is a primary predictor of high blood
      pressure (BP). This study attempted to determine whether there is a gradual
      increase in BP between individuals with two hypertensive parents, one
      hypertensive parent, and normotensive parents and whether this increase is
      apparent with both ambulatory and casual BP assessments in men as well as in
      women. METHODS: A total of 220 healthy men and women, aged 22 to 50 years,
      completed two 24-h ambulatory BP sessions (one work day and one off work day).
      Based on family history information obtained from parents, three groups were
      formed: subjects with two hypertensive parents, one hypertensive parent, and
      normotensive parents. Work and off work days did not differ; analyses were based
      on mean values of the 2 days. RESULTS: Men with two hypertensive parents had
      higher daytime and night-time ambulatory BP than men with normotensive parents.
      Those with one hypertensive parent had intermediate BP levels. Ambulatory BP was
      not associated with family history in women. Also, men with one or two
      hypertensive parents had higher ambulatory BP than women with hypertensive
      parents, whereas offspring of normotensive parents exhibited no sex differences
      in BP. CONCLUSIONS: Elevated systolic and diastolic BP throughout the day and
      night seems to characterize men with two hypertensive parents. In evaluating the
      relationship between family history of hypertension and BP, it is important to
      use ambulatory BP measures, differentiate between individuals with one and with
      two hypertensive parents, and focus on gender differences in BP.

PMID- 16647621
TI  - In the name of the father... and the mother.

PMID- 16647622
TI  - Regression of left ventricular hypertrophy and prevention of stroke in
      hypertensive subjects.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a risk marker for stroke and
      its regression confers protection from stroke. The relationship between serial
      LVH changes and risk of stroke has never been investigated in a mixed population
      of hypertensive subjects with and without LVH. METHODS: In this study, 880
      initially untreated hypertensive subjects (mean age 48 years, office blood
      pressure (BP) 155/98 mm Hg; 24-h BP 137/87 mm Hg) underwent tests including
      echocardiography and 24-h ambulatory BP monitoring at entry and after a median of
      3.5 years, still in the absence of cardiovascular events. RESULTS: Months or
      years after the follow-up study, 34 of these subjects developed a first
      cerebrovascular event (stroke in 21, transient ischemic attack in 13). Event rate
      (x 100 patients per year) was 0.25 among the subjects who never developed
      echocardiographic LVH or with regression of LVH, versus 1.16 among the subjects
      with lack of regression or new development of LVH (log-rank test: P = .00001).
      Serial electrocardiogram (ECG) changes failed to define groups at different risk.
      In a Cox analysis, the risk of cerebrovascular events was 2.8 times higher (95%
      CI: 1.18-6.69) in the subset with lack of regression or new development of LVH
      than in that with LVH regression or persistently normal LV mass. Such effect was
      independent of age (P = .001) and 24-h systolic BP (P = .003). CONCLUSIONS: In a
      mixed hypertensive population with and without LVH at entry, serial changes in
      the echocardiographic indexes of LVH predict subsequent cerebrovascular events
      independently of office and ambulatory BP and other individual risk factors.

PMID- 16647623
TI  - Blunt renal trauma-induced hypertension: prevalence, presentation, and outcome.
AB  - BACKGROUND: Blunt renal trauma (RT) may cause hypertension. We assessed the
      frequency and mechanisms of RT, and blood pressure (BP) outcome after treatment.
      METHODS: We searched the records of all patients referred to our hypertension
      unit and included those of previously normotensive patients who developed
      hypertension within 6 months of RT. RESULTS: Ten of the 17,410 referred patients,
      with a median age of 26 years, developed hypertension 0 to 3 months after a well
      documented RT. Median BP at referral was 170/107 mm Hg. Median glomerular
      filtration rate was 89 mL/min. Five patients had hematuria. Median kidney length
      was 107 mm on the damaged side and 114 mm on the opposite side. Renal artery
      lesions were present in six cases. A pattern of unilateral renin hypersecretion
      and contralateral suppression was present in five of eight cases with unilateral
      RT. Six patients underwent surgery. Seven months after referral, median BP was
      128/79 mm Hg. The BP was <140/90 mm Hg without medication in one patient who did
      not undergo surgery and in three patients who did. CONCLUSIONS: Renal trauma is a
      rare cause of hypertension, mostly in young men. Hypertension is usually renin
      dependent and associated with parenchymal injury. The RT-induced hypertension may
      resolve spontaneously and is amenable to surgery.

PMID- 16647624
TI  - Urotensin II and biomarkers of endothelial activation and atherosclerosis in end
      stage renal disease.
AB  - BACKGROUND: Urotensin II (UTN), a cyclic undecapeptide widely distributed in
      various organs and tissues, is found in high concentration in atheromatous
      lesions. Because UTN accumulates in patients with chronic renal failure, the
      association between plasma UTN and biomarkers of atherosclerosis and endothelial
      activation needs to be better understood. METHODS: We tested by a robust
      statistical approach (Holm method) the association between plasma UTN and
      biomarkers of atherosclerosis and endothelial activation in a population of 191
      patients undergoing chronic hemodialysis. RESULTS: Plasma UTN was significantly
      higher in patients with end-stage renal disease (median: 6.5 ng/mL) than in
      healthy subjects (median: 3.1 ng/mL) (P < .001), and in both patients and control
      subjects it was independent of age and sex. Interestingly, UTN was inversely
      related to fibrinogen (r = -0.50, P < .004), intracellular adhesion molecule-1 (r
      = -0.24, P < .004) and with NO synthesis inhibitor asymmetric dimethyl-arginine
      (r = -0.40, P < .004). These links were paralleled by direct correlations with
      albumin (r = 0.21, P < .006) and with transforming growth factor-beta1 (TGFbeta1)
      (r = 0.36, P < .004). Of note, on multiple regression analysis, these
      associations remained highly significant also after data adjustment for potential
      confounders. CONCLUSIONS: The inverse links between UTN with biomarkers of
      atherosclerosis and endothelial activation suggest that downregulation of UTN may
      be a counter-regulatory response aimed at mitigating cardiovascular damage or
      that UTN itself is a protective factor.

PMID- 16647625
TI  - Urotensin and cardiovascular risk among patients with end-stage renal disease:
      fact or fiction?

PMID- 16647626
TI  - Diabetic nephropathy in pregnancy: suboptimal hypertensive control associated
      with preterm delivery.
AB  - BACKGROUND: Nephropathy complicates 5% to 10% of pregnancies in women with
      diabetes and is associated with adverse outcomes. Given the importance of blood
      pressure (BP) control in reducing cardiovascular and renal complications outside
      of pregnancy, we hypothesized that poorly controlled hypertension in early
      pregnancy among women with diabetic nephropathy would be associated with adverse
      outcomes. METHODS: To examine the impact of hypertensive control in early
      pregnancy on perinatal outcomes, we performed a retrospective cohort study of
      pregnancies complicated by diabetic nephropathy with "Above Target" mean arterial
      pressure (> or = 100 mm Hg; N = 21) and "Below Target" mean arterial pressure (<
      100 mm Hg; N = 22), which approximates the American Diabetes Association and the
      Seventh Report of the Joint National Committee recommended target of 130/80 mm
      Hg, measured at < 20 weeks' gestation. RESULTS: There were no differences in
      maternal age (mean +/- SEM: 27.2 +/- 1.2 v 29.5 +/- 1.0 years), duration of
      diabetes (median, range: 17.5, 13 to 24 v 16, 1 to 25 years), or glucose control
      (glycosylated hemoglobin [HbA1c] 8.0% +/- 0.3% v 8.1% +/- 0.4%) between the Above
      and Below Target groups. The Above Target group had more proteinuria (4.69 +/-
      1.08 v 1.65 +/- 0.43 g/24 h; P = .007) and higher serum creatinine levels (1.23
      +/- 0.17 v 0.85 +/- 0.06 mg/dL; P = .02). The Above Target group was more likely
      to deliver at < 32 weeks' gestation (38.1% v 4.6%; P = .007). The increased risk
      of preterm delivery remained significant after adjusting for duration of diabetes
      and glucose control. CONCLUSIONS: Suboptimal control of hypertension in early
      pregnancy in women with diabetic nephropathy is associated with a significant
      risk of preterm delivery. Improved preconceptional control of hypertension may
      reduce adverse perinatal outcomes in women with diabetic nephropathy.

PMID- 16647627
TI  - The effect of age on hypertension control and management.
AB  - BACKGROUND: Despite guidelines recommending similar blood pressure (BP) treatment
      goals regardless of age, controversy exists regarding treating those > or = 80
      years of age. Whether this affects current practice in terms of differences in BP
      control and number of prescribed antihypertensives by age is unknown. METHODS:
      This was a cross-sectional study of 59,207 outpatients with hypertension treated
      at 10 Veterans Health Administration sites. Outcome measures were BP control (<
      140/90 mm Hg) and number of antihypertensive medications at the patient's last
      study visit. Uncontrolled BP was also categorized by whether systolic, diastolic,
      or both were elevated. RESULTS: Subjects 40 to 49 years and those 50 to 59 years
      of age had better BP control (adjusted odds ratios 1.35 [95% CI = 1.26 to 1.44]
      and 1.22 [CI = 1.17 to 1.28] respectively) compared with subjects 60 to 69 years
      of age; those 70 to 79 years of age and > or = 80 years had worse control (OR =
      0.92 for both; respective CIs = 0.88 to 0.96 and 0.86 to 0.99). Antihypertensive
      medication use increased by successive decade to age 80 years, after which the
      trend reversed. Adjusted mean number of medications by age were: < 40 years,
      2.60; 40 to 49, 2.82; 50 to 59, 2.91; 60 to 69, 3.01; 70 to 79, 3.03; > or = 80
      years, 2.90 (P < .05 in pairwise comparisons). The trend of number of medications
      by age did not vary across hypertension categories, despite systolic hypertension
      increasing and diastolic hypertension decreasing with age. Subjects < 40 years of
      age were taking the fewest medications, followed by subjects > or = 80 years and
      then by those 40 to 49, 50 to 59, 70 to 79, and 60 to 69 years of age.
      CONCLUSIONS: The oldest hypertension patients, despite worse BP control, are
      being treated less aggressively with fewer medications than their younger
      counterparts (those 60 to 79 years of age). Our results suggest that current
      controversy in treating the oldest hypertensive patients is having an impact on
      actual practice.

PMID- 16647628
TI  - Pharmaceutical care program for patients with uncontrolled hypertension. Report
      of a double-blind clinical trial with ambulatory blood pressure monitoring.
AB  - BACKGROUND: Pharmaceutical care programs may be an option to improve blood
      pressure (BP) control in patients with uncontrolled hypertension. The aim of this
      study was to evaluate the efficacy of pharmaceutical care programs in treating
      patients with resistant hypertension. METHODS: In a double-blind randomized
      clinical trial, 71 patients with uncontrolled BP were enrolled in a
      pharmaceutical care program or in a control group and underwent a series of
      cognitive tests. The primary outcome was change in ambulatory BP (ABP) between
      the baseline evaluation and the final visit 6 months later. The secondary
      outcomes were the frequency of drug-related problems and adherence as determined
      by plasma levels of hydrochlorothiazide. RESULTS: The delta-values between the
      intervention and control groups for ABP in the different daily periods, with the
      corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1
      to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic
      BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (
      2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in
      the plasma in 21 of 27 patients in the intervention group that attended to all
      appointments and 24 of 30 patients in the control group (P = .904). CONCLUSIONS:
      The pharmaceutical care program tested in this trial was feasible and showed a
      trend for better BP control in patients with uncontrolled hypertension.

PMID- 16647629
TI  - Oxidant stress and blood pressure responses to angiotensin II administration in
      rats fed varying salt diets.
AB  - To examine the hypothesis that NAD(P)H oxidase (Nox)-derived superoxide
      generation is involved in the development of angiotensin II (ANG II)-induced
      hypertension, we evaluated the responses to ANG II infusion (65 ng/min; osmotic
      mini-pump) for 2 weeks in rats treated with or without apocynin (APO) (inhibitor
      of Nox subunits assembly) in drinking water (12 mmol/L). Rats were grouped
      according to their diets with varying salt content (normal salt [NS], 0.4%; high
      salt [HS], 8%; low salt [LS], 0.03%) given during the 2-week experimental period.
      The variation in salt intake did not alter mean arterial pressure (MAP, recorded
      via pre-implanted arterial catheter) but showed proportionate levels in urinary
      excretion rate of Isoprostaglandin(2alpha) (U(ISO)V; NS, 179 +/- 26; HS, 294 +/-
      38; LS, 125 +/- 7 ng/kg/24 h). Treatment with ANG II increased MAP proportional
      to salt intake (NS, 126 +/- 3 to 160 +/- 5; HS, 116 +/- 4 to 184 +/- 5; LS, 125
      +/- 1 to 154 +/- 5 mm Hg). However, ANG II increased U(ISO)V only in NS rats (250
      +/- 19 ng/kg/24 h) but not in HS or LS rats. In response to ANG II, Nox subunits
      protein expression increased in HS but not in the NS or LS rats. Apocynin
      treatment partially ameliorated these changes in Nox proteins in HS rats but did
      not alter ANG II-induced increases in MAP or U(ISO)V. These data suggest that Nox
      activation may not be the sole factor or alternatively, that a constitutively
      active isoform of Nox is involved in oxidative stress mechanism that is
      associated with dietary salt or ANG II-induced hypertension.

PMID- 16647631
TI  - The role of the epidemiologist in clinical and translational science.

PMID- 16647630
TI  - Young Scholars Award Lecture: Intratubular angiotensinogen in hypertension and
      kidney diseases.
AB  - Recent findings related to the renin-angiotensin system have provided a more
      elaborated understanding of the pathophysiology of hypertension and kidney
      diseases. These findings have led to unique concepts and issues regarding the
      intrarenal renin-angiotensin system. Angiotensinogen is the only known substrate
      for renin that is the rate-limiting enzyme of the renin-angiotensin system.
      Because the level of angiotensinogen in human beings is close to the Michaelis
      Menten constant value for renin, changes in angiotensinogen levels can control
      the activity of the renin-angiotensin system, and its upregulation may lead to
      elevated angiotensin peptide levels and increases in blood pressure. Enhanced
      intrarenal angiotensinogen mRNA or protein levels or both have been observed in
      multiple models of hypertension including angiotensin II-dependent hypertensive
      rats, Dahl salt-sensitive hypertensive rats, and spontaneously hypertensive rats,
      as well as in kidney diseases including diabetic nephropathy, immunoglobulin A
      (IgA) nephropathy, and radiation nephropathy. Renal angiotensinogen is formed
      primarily in proximal tubular cells and is secreted into the tubular fluid.
      Urinary angiotensinogen excretion rates show a clear relationship to kidney
      angiotensin II contents and kidney angiotensinogen levels, suggesting that
      urinary angiotensinogen may serve as an index of the intrarenal renin-angiotensin
      system status. Establishment of concise and accurate methods to measure human
      angiotensinogen may allow clinical studies that would provide important
      information regarding the roles of intrarenal angiotensinogen in the development
      and progression of hypertension and kidney diseases.

PMID- 16647632
TI  - NIH innovation letter.

PMID- 16647633
TI  - NIH Grants.

PMID- 16647634
TI  - Effect of misoprostol on bone mineral density in women with postmenopausal
      osteoporosis.
AB  - OBJECTIVE: To evaluate the effect of misoprostol on bone mineral density in
      postmenopausal women. MATERIALS AND METHODS: The study was performed in a
      randomized controlled prospective manner in 90 women with menopause at
      Suleymaniye Maternity and Women's Diseases Teaching and Research Hospital between
      January and December 2003. Cases were divided into three groups each consisting
      of 30 women who were in menopause for at least 1 year and had t-scores less than 
      1 by dual energy X-ray densitometry (DEXA). Group I was treated with misoprostol
      and calcium, Group II received tibolone and calcium and Group III was given
      calcium only and considered as control group. In all patients, bone mineral
      density in L1-L4 vertebrae, femur neck and Ward triangle were measured by DEXA
      and t and z scores were calculated. RESULTS: All groups were similar
      demographically. Bone mineral density in L1-L4 vertebrae, femur neck and Ward
      triangle in the group treated with misoprostol, increased by 5, 8.1 and 3.6%,
      respectively. In the tibolone group, bone mineral density in L1-L4 vertebrae,
      femur neck and Ward triangle increased by 8.3, 5.3 and 7.8%, respectively. There
      was not a significant difference in t and z-scores and bone mineral density
      measurements between misoprostol and tibolon groups. CONCLUSION: Misoprostol may
      be an alternative treatment for patients with osteopenia and osteoporosis who are
      not suitable for hormone replacement therapy.

PMID- 16647635
TI  - PGE(2) receptors and their intracellular mechanisms in rabbit small intestine.
AB  - The effects of PGE(2) on longitudinal smooth muscle, the intracellular mechanisms
      involved, and the localization of EP receptors were investigated in rabbit small
      intestine. PGE(2) evoked contractions in small intestine that were reduced by
      tetrodotoxin and hexamethonium. 17-Phenyl trinor PGE(2), sulprostone, misoprostol
      and 16,16-dimethyl PGE(2) evoked contractions. Butaprost did not modify
      spontaneous motility. AH 6809 reduced PGE(2) and 17-phenyl trinor PGE(2)-induced
      contractions. Verapamil, Ca(2+) free medium, staurosporine, forskolin,
      theophylline, and rolipram diminished, while IP-20 and H-89 increased PGE(2)
      induced contractions. Western blot analysis showed protein bands of 41kDa for
      EP(1), 71kDa for EP(2) and 62kDa for EP(3) receptors. EP(1), EP(2) and EP(3)
      receptors were detected in neurons of the myenteric and submucosal ganglia, but
      only EP(3) receptors were found in smooth muscle layers. This study did not
      detect EP(4) receptor. PGE(2)-induced contractions would be mediated through
      EP(1) and EP(3) receptors, and voltage-dependent Ca(2+) channels, protein kinase
      C, and cAMP would be implicated in these responses.

PMID- 16647636
TI  - Role of intraluteal prostaglandin F(2alpha), progesterone and oxytocin in basal
      and pulsatile progesterone release from developing bovine corpus luteum.
AB  - The present study examined the role of intra-luteal prostaglandin (PG) F(2alpha),
      progesterone (P4) and oxytocin (OT) on the corpus luteum function by using
      specific hormone antagonists. Luteal cells from the developing CL (days 5-7 of
      the estrous cycle) were exposed to P4 antagonist (onapristone, OP, 10(-4)M), OT
      antagonist (atosiban, AT; 10(-6)M) or indomethacin (INDO; 10(-4)M), for 12h and
      then stimulated with PGF(2alpha) (10(-8)M) for 4h. Pre-treatment of the cells
      with OP, AT or INDO resulted in an increase in P4 secretion in response to
      PGF(2alpha). To examine the temporal effects of P4, OT and PGs on P4 secretion,
      dispersed luteal cells were pre-exposed to OP, AT or INDO for 1, 2, 4, 6 or 12h.
      Prostaglandin F(2alpha) stimulated P4 secretion (P<0.05) after 2h of pre
      exposition. In the microdyalisis study, the spontaneous release of P4 from
      developing CL tissue was of pulsatile nature with irregular peaks at 1-2h
      intervals. Treatment with OP increased the number of P4 peaks (P<0.05), whereas
      AT and INDO significantly reduced the number of P4 peaks detected (P<0.05).
      Interestingly, INDO completely blocked the pulsatile nature in the release of P4,
      but it secretion remained stable throughout the experimental period. These
      results demonstrate that luteal PGF(2alpha), OT, and P4 are components of an
      autocrine/paracrine intra-ovarian regulatory system responsible for the episodic
      (pulsatile) release of P4 from the bovine CL during the early luteal phase.

PMID- 16647637
TI  - Effects of 15d-PGJ(2) on VEGF-induced angiogenic activities and expression of
      VEGF receptors in endothelial cells.
AB  - 15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) upregulates expression of
      vascular endothelial growth factor (VEGF), but may inhibit angiogenesis. We found
      that 15d-PGJ(2) (1-10muM) attenuated all VEGF-induced angiogenic activities in
      human umbilical vein endothelial cells (HUVEC). It blocked almost completely cell
      proliferation, potently reduced migration, assembly into tube-like network on
      matrigel, and growth of capillaries into collagen gel. 15d-PGJ(2) inhibited
      expression of VEGFR-1 and VEGFR-2 receptors both at mRNA and protein levels. This
      inhibition, however, was transient (observed after 6-12h, but not after 24h) and
      weak (20-30%), and could not fully explain inhibition of response to VEGF.
      Accordingly, proliferation was inhibited when 15d-PGJ(2) was added 24h after VEGF
      or in cells stimulated with basic fibroblast growth factor. Interestingly, 15d
      PGJ(2) decreased activities of c-jun and c-myc in HUVEC and overexpression of c
      myc attenuated its antiproliferative effects. This suggests that inhibition of
      this transcription factor by 15d-PGJ(2) contributes to decrease in angiogenic
      response.

PMID- 16647638
TI  - The differential effect of PGE(1) on d-galactosamine-induced nitrosative stress
      and cell death in primary culture of human hepatocytes.
AB  - The pre-administration of PGE(1) reduced inducible nitric oxide synthase (NOS-2)
      expression and cell death induced by d-galactosamine (d-GalN) in cultured rat
      hepatocytes. The present study evaluated the role of nitric oxide (NO) during
      PGE(1) treatment in fully established d-GalN-induced cytotoxicity in cultured
      human hepatocytes. Human hepatocytes were isolated from liver resections by
      classic collagenase perfusion. PGE(1) (1 microM) was administered at 2 h before d
      GalN (40 mM), or 2 or 10 h after d-GalN in cultured hepatocytes. The production
      of NO was inhibited by N-omega-nitroso-l-arginine methyl ester (l-NAME) (0.5 mM).
      Various parameters related to oxidative and nitrosative stress, mitochondrial
      dysfunction, NF-kappaB activation, NOS-2 expression and cell death were evaluated
      in hepatocytes. NO mediated mitochondrial disturbances, nitrosative stress and
      cell death in d-GalN-treated hepatocytes. The administration of PGE(1) 10 h after
      d-GalN enhanced NF-kappaB activation, NOS-2 expression and nitrosative stress.
      Although PGE(1) administered at 2 h before or 2h after d-GalN reduced apoptosis
      and necrosis, its administration 10 h after d-GalN had no beneficial effect on
      cell death. In conclusion, the administration of PGE(1) during advanced d-GalN
      cytotoxicity induced nitrosative stress and lost its cytoprotective properties in
      cultured human hepatocytes.

PMID- 16647639
TI  - Nitric oxide (NO) inhibits prostaglandin E2 9-ketoreductase (9-KPR) activity in
      human fetal membranes.
AB  - Nitric oxide (NO) synthesized by fetal membranes may act either directly
      inhibiting myometrium contractility or indirectly interacting with tocolytic
      agents as prostaglandins (PGs). Here we examined if NO could modulate
      prostaglandin E(2) 9-ketoreductase (9-KPR) activity in human fetal membranes
      (HFM). 9-KPR is the enzyme that converts PGE(2) into PGF(2alpha), the main PGs
      known to induce uterine contractility at term. Chorioamnion explants obtained
      from elective caesareans were incubated with aminoguanidine (AG), an iNOS
      inhibitor, or NOC-18, a NO donor. NOC-18 (2mM) increased PGE(2) production and
      diminished PGF(2alpha) synthesis in HFM. AG presented the opposite effect. When
      we evaluated the activity of 9-KPR by the conversion of [(3)H]-PGE(2) into [(3)H]
      PGF(2alpha) and 13,14-dihidro-15-keto prostaglandin F(2alpha) (the PGF(2alpha)
      metabolite), we found that NOC-18 inhibited 9-KPR activity. Interestingly, AG did
      not elicit any effect on 9-KPR but l-NAME, a non-selective NOS inhibitor,
      significantly increased its activity. Our data suggests that exogenous NO
      inhibits 9-KPR activity in HFM, thus modulating the synthesis of important labor
      mediators as PGF(2alpha).

PMID- 16647640
TI  - The regulation of formation of prostaglandins and arachidonoyl-CoA from
      arachidonic acid in rabbit kidney medulla microsomes by linoleic acid
      hydroperoxide.
AB  - Under physiological conditions, small amounts of free arachidonic acid (AA) are
      released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA
      synthetase (ACS) competitively act on this fatty acid to form prostaglandins
      (PGs) and arachidonoyl-CoA (AA-CoA). In the present study, we investigated the
      effects of linoleic acid (LA) and 13-hydroperoxyoctadecadienoic acid (13-HPODE)
      on the PG and AA-CoA formation from high and low concentrations of AA (60 and 5
      microM) in rabbit kidney medulla microsomes. The kidney medulla microsomes were
      incubated with 60 or 5 microM [(14)C]-AA in 0.1M Tris-HCl buffer (pH 8.0)
      containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors
      of ACS (ATP, MgCl(2) and CoA). After incubation, PG (as total PGs), AA-CoA and
      residual AA were separated by selective extraction using petroleum ether and
      ethyl acetate. LA (10-50 microM) reduced only PG formation from both 60 and 5
      microM AA. 13-HPODE (10-50 microM) also reduced PG formation from 60 and 5 microM
      AA, but the inhibitory potency was much stronger than that by LA. Furthermore, 13
      HPODE had the potential to increase the AA-CoA formation with a decrease in the
      PG formation from 5 microM AA. These results suggest that 13-HPODE, but not LA,
      may shift AA away from COX pathway into ACS pathway under low substrate
      concentration (near physiological concentration of AA).

PMID- 16647641
TI  - The effect of hypoxia on lipid phosphate receptor and sphingosine kinase
      expression and mitogen-activated protein kinase signaling in human pulmonary
      smooth muscle cells.
AB  - Both acute and chronic hypoxia had no effect on S1P(1), S1P(3) or LPA(1) receptor
      transcript expression in human pulmonary smooth muscle cells. However, acute
      hypoxia increased sphingosine kinase SK1/2 and LPP1 mRNA transcript levels, while
      chronic hypoxia increased SK1 mRNA transcript alone. Acute hypoxia had no effect
      on S1P-, PDGF- or phorbol ester (PMA)-stimulated activation of ERK-1/2, but
      increased the ability of S1P to activate p38 MAPK. Chronic hypoxia increased the
      ability of S1P to stimulate the phosphorylation of ERK-1/2. Therefore, we have
      demonstrated for the first time that hypoxia can lead to marked changes in the
      expression of genes involved in S1P production and may modify post S1P receptor
      signal transduction pathways.

PMID- 16647642
TI  - Equol and para-ethyl-phenol stimulate prostaglandin F(2alpha) secretion in bovine
      corpus luteum: intracellular mechanisms of action.
AB  - Corpus luteum (CL) is a reproductive gland that plays a crucial endocrine role in
      the regulation of the estrous cycle, fertility, and pregnancy in cattle. The main
      function of CL is secretion of progesterone (P4), an important hormone for
      establishment a successful pregnancy, whereas prostaglandin F(2alpha)
      (PGF(2alpha)), 17beta-estradiol (E(2)) and testosterone (T) are implicated in the
      regulation of luteolysis. It has been shown that phytoestrogens may disrupt
      numerous reproductive functions on several levels of regulation and via different
      intracellular mechanisms. Using a cell-culture system of steroidogenic cells of
      the bovine CL, we determined effects of active phytoestrogen metabolites (equol
      and para-ethyl-phenol) on PGF(2alpha), P4, and T synthesis in steroidogenic CL
      cells. Moreover, we examined the intracellular mechanisms of phytoestrogen
      metabolite actions. Phytoestrogen metabolites did not affect P4 production in
      steroidogenic CL cells. However, PGF(2alpha) and T were significantly stimulated
      by metabolites of phytoestrogens in the bovine steroidogenic CL cells. To study
      the intracellular mechanism of endogenous E(2) and phytoestrogen metabolites
      action, steroidogenic cells were preincubated with a phospholipase C inhibitor
      (U73122), a protein kinase C inhibitor (staurosporine), an estrogen receptor
      antagonist (ICI) and a transcription inhibitor (actinomycin D) for 0.5h, and then
      stimulated with para-ethyl-phenol, equol or E(2). Only U73122 and staurosporine
      totally reduced the stimulatory effect of E(2) on PGF(2alpha) production by the
      cells. ICI and actinomycin D only partially reduced E(2) action on CL cells. In
      contrast, the stimulatory effect of phytoestrogen metabolites was totally
      inhibited by ICI and actinomycin D. Moreover, in contrast to E(2) action,
      phytoestrogen metabolites did not cause intracellular calcium mobilization in the
      cells. The present study demonstrated that phytoestrogen metabolites stimulate
      PGF(2alpha) secretion in steroidogenic cells of the bovine CL via the estrogen
      receptor-dependent, genomic pathway.

PMID- 16647644
TI  - Patient selection.
AB  - Patient selection is the process by which an evaluating surgeon decides whether
      to accept responsibility for the care and treatment of a potential patient. It is
      assumed the physician has the requisite knowledge to assess the anatomic disorder
      and the technical ability to render appropriate care if needed. The aim of this
      article is to help the less experienced health care professional sort out which
      patients, either by true psychological disorder or personality and behavioral
      traits, pose the highest risk of a poor outcome. An unsatisfactory outcome can be
      measured not only by failure to resolve the disorder but also by expenditure of a
      disproportionate amount of practice resources in achieving resolution of the
      problem.

PMID- 16647645
TI  - Determining causation of work-related upper extremity disorders.
AB  - To determine causation in work-related upper extremity disorders, one must
      appreciate the philosophical constructs used in establishing causation and have
      clear definitions of the disorder in question. The preponderance of evidence does
      not support repetition as a major risk factor for physical injury. Terms such as
      "repetitive stress," "repetitive strain," and "cumulative trauma" should be
      abandoned, and we should educate our patients as to the multiple risk factors for
      upper extremity pain.

PMID- 16647646
TI  - Prevention of delayed recovery and disability of work-related upper extremity
      disorders.
AB  - There is always a psychological component to any illness or injury, and unless it
      is appropriately addressed, such factors can complicate or delay the recovery
      from a work-related illness or injury. When a worker experiences delayed recovery
      and unexpected disability, significant contributing psychosocial factors must be
      assessed for and managed appropriately. A maladaptive belief or understanding
      about the condition and disability by a patient presents an obstacle to
      successful treatment. Using cognitive behavioral therapy techniques may be an
      effective means of managing this challenge for the clinician.

PMID- 16647647
TI  - Ergonomic considerations in work-related upper extremity disorders.
AB  - Correctly applied, an ergonomics approach can reduce the likelihood of work
      induced disorders and can assist in accommodating individuals who have work
      related disorders, but it cannot eliminate disorders that have been mistakenly
      attributed to work by social processes. A contextual model of work-related upper
      extremity disorders is proposed that explicitly acknowledges that factors
      extrinsic to work can shape perceptions of upper extremity disorders and
      influence the process of somatic interpretation and health outcomes. Experiences
      in the United Kingdom of ergonomic regulations associated with computer use and
      the media coverage of work-related upper extremity disorders are used to
      illustrate this model.

PMID- 16647648
TI  - Epidemiology of work-related upper extremity disorders: understanding prevalence
      and outcomes to impact provider performances using a practice management
      reporting tool.
AB  - In 2001, the number of repeated trauma cases accounted for 4% of total workplace
      injuries and 65% of all occupational illnesses, with work-related upper extremity
      disorders accounting for most cases. Because chronic disability leads to the
      highest cost, systematic evaluation of this growing occupational condition is
      needed. This article sheds light on work-related upper extremity disorders by
      understanding the prevalence and pattern for these diagnoses, their impact on
      outcomes influenced by age, gender and geography on metrics such as utilization,
      duration, disability status, and costs. To assess these types of outcomes
      measurements, a good reporting and management system must be in place to allow
      for ongoing evaluation and analysis of data and in the construction of
      intervention programs to improve provider performances and, ultimately, patient
      outcomes.

PMID- 16647649
TI  - The role of imaging of work-related upper extremity disorders.
AB  - Work-related upper extremity disorders can pose a diagnostic and management
      challenge because the nontraumatic disorders that are often believed to be caused
      by repetitive work activities can and do occur without any apparent provoking
      activity and can be caused or associated with many systemic medical conditions.
      One mainstay in the assessment of hand and arm disorders remains imaging. Imaging
      capabilities have made incredible advances with the advent of MRI, CT,
      ultrasound, bone scan, and numerous technologies that enable clinicians to view
      fine details of anatomy and pathology. This article reviews the potential imaging
      choices and clinical indications for work-related injuries of the elbow, hand,
      and wrist.

PMID- 16647650
TI  - Tendinitis and tendinosis of the elbow, wrist, and hands.
AB  - Tendinopathy in the upper extremity continues to be a source of morbidity and
      disability in the working population despite a benign clinical course. Risk
      factors include high force, repetition, and awkward positions. An understanding
      of the pertinent anatomy and pathophysiology should help clinicians in the
      management of these conditions. Tension overload and shear stress are the two
      mechanisms most likely responsible for most upper extremity tendinopathies.
      Clinical presentation includes localized pain and tenderness. Most treatment
      options have yet to undergo evaluation for efficacy in well-designed clinical
      trials, yet there is a generally favorable response to nonoperative or
      conservative management. Cases resistant to conservative treatment may require
      surgical intervention.

PMID- 16647651
TI  - Ligament injuries of the hand and wrist.
AB  - The human hand is one of the most amazing instruments we possess. Ligament
      injuries to the hand and wrist are common occupational injuries. These injuries
      can be diagnosed using thorough history and physical examination skills in
      conjunction with diagnostic imaging. Prompt diagnosis and treatment of these
      injuries are crucial, because many injuries heal with minimal decrease in
      function if they are treated early without allowing them to become chronic. When
      these injuries are discovered late, not only does treatment become more difficult
      but also traumatic arthritis frequently develops. A brief anatomic description
      follows each of the most common ligament sprains and strains of the hand and
      wrist and their evaluation and treatment.

PMID- 16647652
TI  - Compression neuropathies of the upper extremity.
AB  - Nerve compression syndromes of the upper extremity occur at predicable locations.
      The diagnosis of nerve compression or nerve entrapment is based on the neurologic
      and electrodiagnostic examinations. The anatomy, neurophysiology, and
      electrodiagnosis of nerve compression are discussed. Common and uncommon
      compression and entrapment syndromes of the upper extremity are described. Errors
      in diagnosis occur when the neurologic or electrodiagnostic examinations are
      incomplete or inaccurate.

PMID- 16647653
TI  - Work-related carpal tunnel syndrome: the facts and the myths.
AB  - Carpal tunnel syndrome is a medical disease, not an injury, although symptoms may
      occur in association with certain physical activities of the upper extremity. The
      concept of work-related carpal tunnel syndrome has grown to such proportion as to
      be problematic for society, having spawned health care industries to support a
      cultural concept and a largely mythical medical paradigm. Because of these social
      and economic forces, cultural perceptions and expectations have adjusted to this
      flawed medical model. Success in improving patient management and making the best
      use of sound medical evidence depends on the concurrent use of educational
      strategies addressing social influences and attitudinal changes of practicing
      physicians, patients, and third-party administrators. The promotion of evidence
      based medicine is key. This article discusses these controversies and suggests
      ways of managing carpal tunnel syndrome.

PMID- 16647654
TI  - Occupational hand infections.
AB  - Prompt diagnosis and treatment of hand and upper extremity infections is
      imperative because they have the potential to be life threatening and pose a risk
      of functional impairment. Serious infections may result in prolonged
      hospitalization and resultant loss of productivity. The mainstay of treatment
      continues to be antibiotic therapy, heat, elevation, adequate surgical drainage,
      and debridement. Prompt specialty consultation should be obtained in cases in
      which there is a doubt about the diagnosis or when there is failure to improve in
      the face of seemingly appropriate treatment.

PMID- 16647655
TI  - Hand dermatitis and nail disorders of the workplace.
AB  - Dermatitis and nail bed disorders form a large percentage of occupational
      conditions that affect the hands. This article briefly discusses some of the more
      common causes and presentations of these conditions. Most of these of the
      conditions can occur in the workplace and outside of it, so a careful evaluation
      is necessary to determine the work relatedness of a given condition.

PMID- 16647656
TI  - Rheumatic diseases that can be confused with work-related upper extremity
      disorders.
AB  - Rheumatic illnesses are a common cause for musculoskeletal complaints in the
      general population. All ages can be affected, including people in the prime of
      their working years. Secondary problems, such as entrapment neuropathies,
      enthesopathies, and Raynaud's syndrome, can be associated with various
      inflammatory arthritides. A detailed history and physical are the most important
      tools in screening for potential inflammatory disease in workers with upper
      extremity complaints.

PMID- 16647657
TI  - High pressure injection injuries of the hand.
AB  - High-pressure injection injuries of the hand represent one of the most serious
      surgical emergencies of the upper extremity. It is imperative to understand the
      mechanism of injury and the parts that take place for this injury to occur
      (material, pressure, site of injury). Prompt recognition and treatment may alter
      the final outcome.

PMID- 16647658
TI  - Fingertip injuries.
AB  - The fingertip is a complex anatomic unit highly specialized in function and
      particularly prone to injury. Its complex design and the difficulty of secondary
      repairs demand great care in initial evaluation, diagnosis, and treatment for
      optimal long-term outcome. The goals of treatment should be to preserve length,
      maintain sensation, mobilize early, return function expediently, and be mindful
      of cosmesis.

PMID- 16647659
TI  - Work-related burns.
AB  - Work-related upper extremity burns often occur. The cause directs the course of
      action. Thermal burns should be assessed for system alterations, and depth of
      burn should be determined. Deep partial-thickness burns and more severe burns
      require a specialist evaluation. Chemical burns must be irrigated and the agent
      identified. Some chemical burns, such as those that involve phenols and metal
      fragments, require specific topical applications before water lavage.
      Hydrofluoric acid burns can cause life-threatening electrolyte abnormalities with
      a small, highly concentrated acid burn. The goal with any extremity burn is to
      provide the patient with a multidisciplinary team approach to achieve a
      functional, usable extremity.

PMID- 16647660
TI  - Factitious disorders.
AB  - Factitious disorders reside under the broad umbrella of dysfunctional syndromes.
      This article is meant specifically to focus on common patterns of upper extremity
      factitious illness. It is intended to emphasize recognition, differential
      diagnosis, and problems related to misdiagnosis. It is not devoted to treatment,
      which is a separate issue.

PMID- 16647661
TI  - Complex regional pain syndrome type I in the upper extremity.
AB  - Complex regional pain syndrome (CRPS) remains a challenging condition for
      physicians to treat since the earliest descriptions dating back to the Civil War.
      It has been most commonly reported after traumatic injury or fracture; however,
      many other causes have been documented. This article focuses on CRPS type 1 as it
      pertains to the upper extremity. In general, patients who have complex regional
      pain syndrome suffer from pain, sensory changes, edema, sweating, and temperature
      disturbance in the afflicted extremity. Chronic changes can involve the skin,
      nails, and bone. The pathophysiology of this condition remains unclear and is
      probably multifactorial, involving persistent inflammation, the sympathetic
      nervous system, the central nervous system and external stimuli. Treatment should
      be based on a multidisciplinary experienced team approach that is focused on
      functional restoration. Future research will provide insight into pathophysiology
      and optimal treatment regimens.

PMID- 16647662
TI  - Fibromyalgia and myofascial pain syndromes and the workers' compensation
      environment: an update.
AB  - Fibromyalgia and myofascial pain syndromes are terms used to describe a
      constellation of complaints ranging from generalized aches to specific tender
      trigger points often accompanied by fatigue, depression, and sleep disturbances.
      In the past 5 years, research has been directed primarily at determining the
      pathophysiology of fibromyalgia and myofascial pain syndromes and the treatment
      of patients' comorbidities to alleviate their symptomatology. Controversy exists
      as to whether fibromyalgia and myofascial pain syndromes represent a specific
      pathology or are merely terms to describe clinical conditions that provide
      patients with the reassurance that their symptoms are real and help clinicians
      with therapeutic direction. In the occupational health setting, this uncertainty
      can lead to significant difficulty in determining short- and long-term disability
      and assigning culpability to an individual's work environment.

PMID- 16647663
TI  - Occupational and physical therapy for work-related upper extremity disorders: how
      we can influence outcomes.
AB  - Upper extremity disorders in the workplace continue to be an economic strain on
      society. Physical and occupational therapy plays a crucial role in the management
      of the disorders. Medical providers should use therapists whose treatments
      demonstrate improvement in function and provide superior outcomes. Skilled
      therapy intervention requires that a therapist be able to identify and treat an
      injured worker in a holistic manner by looking at the whole individual, including
      issues that involve mechanical dysfunctions, psychosocial issues that include job
      satisfaction, and other age-related organic comorbidities. Therapists who work
      with injured employees must be highly skilled in identifying behavioral and
      organic disorders and must be confident in communicating these findings to
      various members of the health care team to help facilitate further medical
      testing.

PMID- 16647664
TI  - Worker's compensation litigation of the upper extremity claim.
AB  - This article presents an overview of the issues presented to physicians and
      lawyers in evaluating, treating, litigating, and concluding an upper extremity
      workers' compensation claim. This analysis includes a review of the unique
      considerations involved in the workers' compensation patient/claimant, a general
      examination of workers' compensation law, and the interplay between litigation
      and the medical management of the patient.

PMID- 16647665
TI  - Primary health care by midwives: comprehensive and competent health services for
      women.

PMID- 16647666
TI  - Metabolic syndrome: screening, diagnosis, and management.
AB  - Metabolic syndrome, a growing issue in women's health, is a cluster of health
      findings that increase the risk of cardiovascular events. The prevalence of
      metabolic syndrome is higher in women and is linked to several conditions unique
      to women's health, including polycystic ovary syndrome, gestational diabetes,
      pregnancy-induced hypertension, and female sexual dysfunction. Risk factors,
      screening strategies, and therapeutic management of metabolic syndrome in women
      are discussed.

PMID- 16647667
TI  - Clinical controversies in screening women for thyroid disorders during pregnancy.
AB  - Subclinical hypothyroidism and/or the presence of thyroid peroxidase antibodies
      (TPOAb) may be associated with subfertility, infertility, spontaneous abortion,
      placental abruption, preterm delivery, gestational hypertension, preeclampsia,
      postpartum thyroid dysfunction, depression (including postpartum depression), and
      impaired cognitive and psychomotor child development. In November 2002, the
      American Association of Clinical Endocrinologists (AACE) released new guidelines
      for clinical practice for the diagnosis and treatment of hyperthyroidism and
      hypothyroidism, which includes a new thyroid-stimulating hormone (TSH) reference
      range of 0.3 to 3.0 mIU/L. Recently, the AACE recommended screening all women
      considering conception and/or all gravid women in the first trimester for thyroid
      dysfunction. However, the American College of Obstetricians and Gynecologists
      (ACOG) and the United States Preventive Services Task Force (USPSTF) have not
      endorsed these recommendations. This article reviews the evidence regarding
      screening women during pregnancy for subclinical hypothyroidism and/or the
      presence of thyroid peroxidase antibodies.

PMID- 16647668
TI  - Common problems of urination in nonpregnant women: causes, current management,
      and prevention strategies.
AB  - This article uses a case-based approach to review common problems of urination in
      nonpregnant women, including overactive bladder; stress, urge, and mixed
      incontinence; and retention and prolapse. Up-to-date clinical issues related to
      assessment, diagnosis, treatment, and follow-up are reviewed, with a discussion
      of underlying pathophysiology and prevention strategies. Suggestions are made for
      relevant curriculum content at both the basic and advanced levels of advanced
      practice education.

PMID- 16647669
TI  - Management of migraine headaches.
AB  - With 17% to 18% of women suffering from migraine headaches, clinicians will often
      be asked by their patients to prescribe medication. Migraine is an episodic
      chronic disease that is best managed with an overall treatment plan, rather than
      treated as an acute illness that is managed with sporadic medications. Realistic
      goals for the long-term management of migraine are based on patient education and
      an ongoing discussion between patient and provider. This article reviews the
      clinical presentation of migraine and recommendations for both acute and
      preventive treatment, including complementary therapies. "Red flags" that could
      be signs of more serious neurologic illness are presented. The management of
      migraine in pregnancy is also reviewed.

PMID- 16647670
TI  - Assessing and managing women with depression: a midwifery perspective.
AB  - Women are at disproportionate risk for depression. Depression often goes
      untreated because of lack of recognition by providers. The Institute of Medicine
      maintains that primary care providers are essential in the management of mental
      health disorders. The assessment and management of depression in women are
      sensitive topics and may require advanced training and skills.

PMID- 16647671
TI  - Eating disorders and women's health: an update.
AB  - Anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified
      have a significant impact on the health care and childbearing outcomes of the
      female population. Primary care contact for gynecologic care, childbearing, or
      infertility can serve as a critical entry point for the initial recognition of
      potentially devastating disorders that may result in permanent impairment and/or
      chronic debilitation. This review addresses the nature and prevalence of eating
      disorders and the management of pregnancy complicated by an active eating
      disorder or a history of an eating disorder. Genetic influences and
      intergenerational transmission of eating disorders are discussed. Finally, the
      increased risk for postpartum depression among women with a current or past
      eating disorder is examined. Factors critical to improving pregnancy outcome and
      reducing the risk for exacerbation or relapse in the postpartum period are
      identified.

PMID- 16647672
TI  - Assessment and management of the obese adult female: a clinical update for
      providers.
AB  - Obesity is epidemic in the United States, affecting 61% of adults and 14% of
      children. Today's health care providers should recognize obesity as a chronic
      disease and offer up-to-date information and management. Treatment options
      currently available are diet and behavior modification, medications, and surgical
      procedures. Implications for clinical practice include recognition of the
      problems associated with obesity, education of current patients as well as young
      women who may become patients, and appropriate diagnosis and management or
      referral.

PMID- 16647673
TI  - Perceptions and use of smoking cessation in nurse-midwives' practice.
AB  - The objective of this study was to examine Ohio nurse-midwives' perceptions and
      use of a smoking cessation protocol in assisting pregnant smokers. The total
      population of licensed Ohio nurse-midwives (n = 300) was surveyed by using a
      cross-sectional survey design. Only 4 of 10 items that assessed a nationally
      recommended method of promoting smoking cessation were done by 50% or more of
      respondents. Few nurse-midwives identified barriers to counseling pregnant
      patients who smoked, but the most common were lack of time (14%) and not knowing
      where to send pregnant smokers for treatment (14%). Most respondents believed
      that nicotine replacement therapy (NRT) would be most likely to reduce the number
      of pregnant smokers (74%), yet few (26%) were confident in their ability to
      prescribe/recommend nicotine replacement therapy. Respondents more likely to use
      5 A's can be characterized as the following: had higher efficacy expectations in
      their ability to communicate issues about the 5 A's and had higher outcome
      expectations regarding the effects of using the 5 A's. Nurse-midwife training
      programs and continuing education needs to include current research in nicotine
      replacement therapy use in pregnant patients and 5 A's techniques to assist
      pregnant smokers in quitting.

PMID- 16647674
TI  - Intimate partner violence screening practices of certified nurse-midwives.
AB  - It is estimated that 324,000 pregnant women are abused by their partners in the
      United States each year. The purpose of this qualitative study was to explore the
      intimate partner violence-screening practices of certified nurse-midwives (CNMs).
      In-depth interviews were conducted with a sample (n = 8) of CNMs, and the data
      were analyzed by using with-case and across-case methods. The findings
      demonstrate that the midwives were inconsistent in their intimate partner
      violence-screening practice during pregnancy and increase or decrease screening
      in response to a woman's cultural background. Screening in a culturally competent
      manner is expected of all clinicians, but the demands of an increasingly complex,
      culturally diverse practice environment make it difficult. Consistent intimate
      partner abuse screening in a culturally competent manner is a challenge for all
      primary care providers.

PMID- 16647675
TI  - Caring for a woman at high risk for type 2 diabetes.
AB  - Women who are obese with a history of gestational diabetes are at risk for
      developing type 2 diabetes and metabolic syndrome. A weight loss of as little as
      15 pounds can decrease these long-term risks. This case presentation reviews
      practical issues related to encouraging women to make important lifestyle changes
      and to adhere to taking cholesterol-lowering medications.

PMID- 16647679
TI  - Genetic variations of the Plasmodium vivax dihydropteroate synthase gene.
AB  - Dihydropteroate synthase gene of Plasmodium vivax was recently identified. In the
      present study, the sequences of the dyhydropteroate synthase gene of 68 P. vivax
      isolates from various geographic areas were compared. Sequencing revealed limited
      polymorphism at codons 383 and 553 in all analyzed samples. Interstrain analysis
      showed several genotypic variations in the tandem repeats domain which produce
      length polymorphism between different parasite isolates.

PMID- 16647680
TI  - Immuno-diagnosis of bubaline fasciolosis with Fasciola gigantica cathepsin-L and
      recombinant cathepsin L 1-D proteases.
AB  - Fasciola gigantica cathepsin-L cysteine proteinase and recombinant cathepsin L 1
      D were assessed for their potential in the immuno-diagnosis of F. gigantica
      infection in buffaloes. A diagnostic ELISA, based on these two antigens, was
      developed to detect antibodies against F. gigantica in water buffaloes.
      Sensitivity of the ELISA was assessed using sera from buffaloes experimentally or
      naturally infected with F. gigantica from F. gigantica endemic areas and its
      specificity by probing the sera of the host from F. gigantica non-endemic area.
      Our earlier studies under experimental setting showed 100% sensitivity of
      cathepsin-L ELISA in the diagnosis of fasciolosis in buffaloes, with the earliest
      detection of infection at 4 weeks post-infection. However, under field situation
      of natural F. gigantica infection, this sensitivity declined to 97.1% but
      specificity of the test remained 100%. Cross-reactivity of the antigen was
      checked with Schistosoma indicum, S. spindale, Paramphistomum epiclitum,
      Gastrothylax spp., Gigantocotyle explanatum, hydatid and Strongyloides papilossus
      in the bubaline host, naturally infected with these helminths. F. gigantica
      cathepsin-L and the recombinant cathepsin L-1D does not cross-react with these
      helminth parasites in natural mono or mixed infection of the host. The present
      ELISA contributes a relatively sensitive and reliable tool for the early
      serodiagnosis of bubaline fasciolosis.

PMID- 16647681
TI  - The importance of understanding the local context: women's perceptions and
      knowledge concerning malaria in pregnancy in rural Malawi.
AB  - A current problem of malaria prevention programmes is that not enough attention
      is paid to understanding the local socio-cultural context prior to programme
      implementation. The aim of this study is to discover how Yao women in rural
      Malawi understand and explain malaria in pregnancy, how they perceive it and what
      type of knowledge they have on it. Women's knowledge of the adverse effects of
      malaria in pregnancy is also investigated. At first phase a total of 34 in-depth
      interviews were conducted. At second phase a KAP survey (n=248) was conducted for
      cross-validation of the qualitative information. The findings showed that there
      is neither a vernacular word for malaria nor malaria in pregnancy. Women used a
      local word, malungo, to refer to malaria. Malungo is an ambiguous disease term
      because of its multiple meanings which are used interchangeably to refer to many
      types of feverish illnesses of various causes, not only malaria. Most women did
      not perceive malungo during pregnancy as a serious illness. There were several
      other diseases from anaemia, STDs to cholera etc. that were perceived to be more
      dangerous than malungo. The local meaning of malungo also entailed an assumption
      that it is a common but fairly harmless illness. Women had limited knowledge of
      the adverse effects of malaria in pregnancy, the best-known adverse effect being
      miscarriage (28%, 52/189). A socio-cultural understanding of the implementation
      context is prerequisite for planning meaningful programmes for the pregnant women
      in rural Africa.

PMID- 16647682
TI  - Change in pulse wave velocity throughout normal pregnancy and its value in
      predicting pregnancy-induced hypertension: a longitudinal study.
AB  - OBJECTIVE: We longitudinally examined the changes of brachial to ankle
      distensibility using pulse wave velocity (PWV) throughout pregnancy and its
      difference between normal pregnancy and pregnancy-induced hypertension (PIH)
      groups. STUDY DESIGN: One hundred and eighty-three pregnant women were included
      in this study. The PWV examinations were performed in a longitudinal way during
      the first, second, and third trimesters of pregnancy, and immediately and 1 month
      after delivery. RESULTS: In normal pregnancies, the PWV significantly decreased
      at the second trimester, increased from the third trimester through immediately
      after delivery, and decreased again at 1 month after delivery. In PIH patients,
      it increased in proportion to the progression of gestation. CONCLUSION: We
      monitored the longitudinal changes in PWV and constructed a PWV normogram during
      pregnancy. The predictive value of PWV and blood pressure for PIH was higher than
      that of blood pressure alone, suggesting the usefulness of measuring PWV to
      predict PIH.

PMID- 16647683
TI  - Inhibitory effect of leptin on human uterine contractility in vitro.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of leptin on
      human uterine contractility in vitro. STUDY DESIGN: Biopsies of human myometrium
      were obtained at elective cesarean section (n = 18). Dissected myometrial strips
      suspended under isometric conditions, undergoing spontaneous and oxytocin-induced
      contractions, were exposed to cumulative additions of leptin in the concentration
      range of 1 nmol/L to 1 micromol/L. Control strips were run simultaneously.
      Integrals of contractile activity were measured using the PowerLab hardware unit
      and Chart v3.6 software. RESULTS: Leptin exerted a potent and cumulative
      inhibitory effect on spontaneous and oxytocin-induced contractions compared to
      control strips. The mean maximal inhibition values were as follows: 46.794 +/-
      5.133% (n = 6; P < .001) for spontaneous contractions and 42.323 +/- 3.692% (n =
      6; P < .001) for oxytocin-induced contractions. There was an apparent reduction
      in both frequency and amplitude of contractions. CONCLUSION: This physiologic
      inhibitory effect of leptin on uterine contractility may play a role in the
      dysfunctional labor process associated with maternal obesity, and the resultant
      high cesarean section rates.

PMID- 16647684
TI  - Prospective analysis of occurrence and management of breakthrough bleeding during
      an extended oral contraceptive regimen.
AB  - OBJECTIVE: The purpose of this study was to assess the bleeding patterns of an
      extended oral contraceptive (OC) regimen and management of breakthrough
      bleeding/breakthrough spotting (BTB/BTS). STUDY DESIGN: This was a single-center
      prospective analysis of self-rated menstrual flow during a 21/7-day versus a 168
      day extended regimen of on OC containing 3 mg of drosperinone and 30 mcg of
      ethinyl estradiol (DRSP/EE) with institution of a randomized protocol to manage
      BTB/BTS. RESULTS: Of the 111 patients initiating the extended OC regimen, 102
      (92%) completed the 168-day regimen. Subjects having a heavier daily flow rating
      during the 21/7-day pre-extension cycle had greater daily flow ratings (P < .001)
      and tended to have earlier occurrence of BTB during the extended regimen (P =
      .07) than subjects with lighter daily flow ratings. If BTB/BTS of at least 7
      consecutive days occurred, patients were randomized to taking a 3-day hormone
      free interval (HFI) versus continuing active pills. Instituting a 3-day HFI was
      significantly more effective in resolving BTB/BTS than continuing active pills (P
      < .0001). Patients with heavier daily flow ratings during the 21/7-day cycle were
      not more likely to be randomized for BTB/BTS than those with lighter flow ratings
      (P = .53). CONCLUSION: A 168-day extended regimen of DRSP/EE had an acceptable
      bleeding profile with a high continuation rate. Bleeding during the extended
      cycle was effectively managed with institution of a 3-day HFI.

PMID- 16647685
TI  - Premature rupture of the fetal membranes: is the amnion the major determinant?
AB  - OBJECTIVE: The objective of the study was to evaluate the relative contributions
      of amnion and chorion to the strength of fetal membranes and to correlate these
      findings with gestational age. STUDY DESIGN: Fetal membranes from 78 pregnancies
      were tested for biaxial puncture force using a blunt, instrumented probe with a
      low-force load cell connected through a load cell conditioner to an oscilloscope.
      The average of 2 to 4 tests performed on independent regions of the membrane was
      recorded. Means and SDs were calculated through the gestational age ranges of
      less than 32, 32 to 36, or 37 weeks or longer. Linear regression analysis was
      performed across gestational age after grouping data by labor and mode of
      delivery. RESULTS: There were trends toward decreasing puncture force with
      gestational age for both chorioamnion and amnion for both vaginal deliveries and
      cesarean sections. The trends were significant by linear regression for labored
      deliveries but not unlabored cesarean sections for both chorioamnion and amnion
      alone. There was no trend in chorion puncture force with either gestational age
      or delivery mode and the mean puncture force values were, on average, half those
      for the amnion. CONCLUSION: The amnion is significantly stronger than the chorion
      when subjected to biaxial strength testing. The amnion but not the chorion is
      significantly affected by the chemical and mechanical changes during gestation
      and the labor process. These data will help direct future studies on the effects
      of clinical and molecular modulators of inflammation on membrane rupture
      thresholds with special emphasis on the biochemical and structural changes in the
      amnion.

PMID- 16647686
TI  - SPI-C and STAT6 can cooperate to stimulate IgE germline transcription.
AB  - SPI-C is a novel ETS protein that is expressed in B lymphocytes. No target gene
      for SPI-C has so far been defined. We have performed a yeast two-hybrid screen
      using SPI-C as bait in order to further analyze the functional role of this
      orphan transcription factor. We found that SPI-C interacted specifically with the
      C-terminus of STAT6 in yeast. By co-immunoprecipitation in transfected COS7 cells
      the physical interaction between SPI-C and STAT6 was confirmed. Furthermore, this
      protein-protein interaction is functional since we could demonstrate that SPI-C
      and STAT6 stimulated IL4 induced Iepsilon transcription synergistically but only
      when both proteins bound to DNA. Thus, a protein interaction between SPI-C and
      STAT6 is the basis for a novel mechanism for regulation of IL4 induced gene
      expression.

PMID- 16647687
TI  - Sulfation is required for bone morphogenetic protein 2-dependent Id1 induction.
AB  - Different reports have suggested the dependence of bone morphogenetic protein
      (BMP) activity on the sulfated glycosaminoglycan (GAG) chains found in
      proteoglycans. However, the requirement of sulfated molecules in early BMP-2
      signaling responses has not been established. We have used sodium chlorate to
      inhibit sulfation in C2C12 cells and have analyzed BMP-2 induction of Id1. We
      show here that sulfation inhibition strongly decreases the specific and early
      induction of Id1 at the transcriptional level. This effect is not reverted by the
      addition of extracellular components, such as GAGs or extracellular matrix (ECM).
      The inhibition of GAG incorporation into proteoglycans, or their removal by GAG
      lyases, does not mimic the negative effect on Id1 expression, while sulfation
      inhibition also represses the Id1-induction exerted by a constitutively active
      form of the BMP receptor, suggesting that BMP-2-mediated Id1 induction has an
      intracellular requirement for sulfated molecules.

PMID- 16647688
TI  - Pre-adsorbed type-I collagen structure-dependent changes in osteoblastic
      phenotype.
AB  - Type-I collagen is the most abundant extracellular matrix in bones and modulates
      various functions of osteoblasts. We prepared two different structures of type-I
      collagen on tissue culture grade polystylene (TCPS) surfaces, one is feltwork
      structure of filamentous molecules from acid solutions (ACs) and the other is
      network structure of fibrils from neutral solutions (NCs), to examine effects of
      the structures on the maturation process of osteoblast-like cells. No significant
      differences of cell proliferation were observed between TCPS and ACs, but NCs
      delayed the proliferation. In initial cell attachment, the cells on ACs had tense
      lamellipodia with sharp tips, while those on NCs had loose lamellipodia. No
      detectable differences in levels of expressed integrin alpha2- and alpha5
      subunits were observed between the structures. Although the matrix mineralization
      in NCs was also delayed in comparison with TCPS and ACs, fully mineralized levels
      in NCs were the same as those of TCPS and ACs. In addition, although we examined
      the effects of densities of pre-adsorbed collagen molecules on osteoblast
      maturation, the effects were less serious than those of the structures. This
      study suggests that the structures of collagen affect proliferation and
      mineralization of osteoblast-like cells.

PMID- 16647689
TI  - Task reconfiguration and carryover in task switching: an event-related potential
      study.
AB  - This study investigated the electrophysiological correlates of the processes
      involved in task switching. A pair-wise task-switching paradigm was used where
      each trial comprised two tasks that were either the same (task repeat) or
      different (task switch). In the paradigm, task-switch and repeat trials are
      compared in conditions of foreknowledge and non-foreknowledge of the forthcoming
      task type and during different response-stimulus intervals (RSIs). The results of
      this study show that, before the second task began in a task-pair trial, i.e.,
      during the RSI, there was a CNV-like negativity for all trials. This indicates a
      general anticipatory effect. In foreknowledge conditions, there is an additional
      switch-specific reconfiguration process followed by a task-specific (including
      both switch- and repeat-related) preparatory process. During the post-task 2
      stage, P3b was found to be smaller in switch trials than in repeat trials. Such
      differential P3b between switch and repeat trials appeared earlier and larger in
      foreknowledge than in non-foreknowledge conditions. The results of this study
      support the existence of advance preparation and uphold the role of carryover
      effects in task switching.

PMID- 16647690
TI  - Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function.
AB  - The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-))
      represents a viable animal model for human SSADH deficiency and is characterized
      by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma
      aminobutyric acid (GABA) in brain, blood, and urine. In physiological
      concentrations, GHB acts at the GHB receptor (GHBR), but in high concentrations
      such as those observed in the brains of children with SSADH deficiency, GHB is
      thought to be a direct agonist at the GABABR receptor (GABABR). We tested the
      hypothesis that both GHBR and GABABR-mediated function are perturbed in SSADH
      deficiency. Therefore, we examined the high affinity binding site for GHB as well
      as the expression and function of the GABABR in mutant mice made deficient in
      SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific
      GABABR antagonist, [3H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-)
      when compared to wild type control animals (SSADH(+/+)), particularly in
      hippocampus. GABABR-mediated synaptic potentials were decreased in SSADH(-/-).
      Immunoblot analysis of GABABR1a, R1b, and R2 in SSADH(-/-) indicated a trend
      towards a region-specific and time-dependent decrease of GABABR subunit protein
      expression. There was no difference between SSADH(-/-) and wild type in binding
      of either [3H]GHB or a specific GHBR antagonist to the GHBR. These data suggest
      that the elevated levels of GABA and GHB that occur in SSADH(-/-) lead to a use
      dependent decrease in GABABR-mediated function and raise the possibility that
      this GHB- and GABA-induced perturbation of GABABR could play a role in the
      pathogenesis of the seizures and mental retardation observed in SSADH deficiency.

PMID- 16647691
TI  - Does neuroglobin protect neurons from ischemic insult? A quantitative
      investigation of neuroglobin expression following transient MCAo in spontaneously
      hypertensive rats.
AB  - Neuroglobin (NGB) is a recently characterized heme globin expressed primarily in
      retinal nerve cells and at very low levels in endocrine-active regions of
      vertebrate brains. When artificially over-expressed, NGB reduces the infarct size
      observed after transient Middle Cerebral Artery occlusion (tMCAo) in rats. This
      study addresses the post-ischemic NGB expression in vivo. Ten Spontaneously
      Hypertensive Rats (SHRs) were randomized to tMCAo (n = 6) or sham (n = 4), and
      euthanized 24 h later. NGB mRNA expression was determined by means of
      quantitative Reverse Transcription Polymerase Reaction (qRT-PCR). Thirteen
      animals subjected to either 90 min tMCAo (n = 7) or sham (n = 6) surgery, were
      euthanized 1 week after surgery. Post-ischemic expression of NGB and the neuronal
      marker NeuN was studied using free-floating immunohistochemistry. Design-based
      stereological quantification of NGB- and NeuN-positive cells in the striatum was
      performed using the optical fractionator. Significantly less NGB mRNA was
      expressed in the ischemic hemispheres of tMCAo animals after 24 h (P < or =
      0.002). At the protein level, we found a significantly lower number of NGB- and
      NeuN-positive striatal neurons in tMCAo rats (P < or = 0.004). NGB expression was
      mainly confined to the hypothalamus and amygdala. Less than one out of every two
      thousand neurons expressed NGB in the striatum. In the ischemic territory we did
      not observe selective sparing of NGB expressing neurons. No significant change in
      the NGB/NeuN ratio was observed. Our data indicate that endogenous expressed NGB
      does not provide protection against ischemic injury induced by tMCAo in SHRs.

PMID- 16647692
TI  - Deep brain stimulation of the substantia nigra pars reticulata exerts long
      lasting suppression of amygdala-kindled seizures.
AB  - Deep brain stimulation (DBS) has been used to treat a variety of neurological
      disorders including epilepsy. However, we have limited knowledge about effective
      target areas, optimal stimulation parameters, and long-term effect of DBS on
      epileptic seizures. Here we examined the effects of DBS of the substantia nigra
      pars reticulata (SNr) on amygdala-kindled seizures. Microwire electrodes were
      implanted into the SNr and amygdala of adult male rats. When stage 5-kindled
      seizures were achieved by daily amygdala kindling, high frequency stimulation was
      delivered to the SNr bilaterally 1 s after cessation of kindling. Our DBS
      protocol completely blocked kindled seizures in 10 out of 23 (43.5%) rats
      studied. Furthermore, when the same amygdala kindling procedure was performed 24
      h later without DBS, the kindling failed to elicit any seizure signs in 6 of
      these 10 rats. Some of the post-DBS period of seizure suppression lasted for up
      to 4 days. In other 3 rats, only mild stage 1 to 2 seizures appeared following
      amygdala kindling. Only 1 of the 10 rats for which DBS had blocked kindled
      seizures exhibited full-scale 5 stage-kindled seizures 24 h after DBS. These
      results suggest that highly plastic neural networks are involved in amygdala
      kindled seizures and that DBS, if well timed with the onset of amygdala kindling,
      may exert long lasting effects on the networks that may prevent the recurrence of
      kindled seizures.

PMID- 16647693
TI  - Minocycline treatment prevents cavitation in rats after a cortical
      devascularizing lesion.
AB  - Minocycline, a second-generation tetracycline, has been shown to possess
      neuroprotective effects in animal models of stroke. Pial vessel disruption in
      adult Wistar rats leads to a cone-shaped cortical lesion and turns into a fluid
      filled cavity surrounded by a GFAP+ glia limitans 21 days after injury. This
      mimics the clinical situation in lacunar infarcts. Minocycline was given
      intraperitoneally at a dose of 45 mg/kg 1 and 12 h after lesioning, followed by
      22.5 mg/kg twice daily until 6 days after lesioning. Control rats received
      intraperitoneal injections of equivalent volumes of saline. Cavitation was
      prevented in five out of six minocycline-treated animals and the glia limitans
      did not appear as the space was filled with GFAP+ reactive astrocytes. However,
      the number of activated microglia showed no difference between minocycline
      treated and -untreated groups. Minocycline did not reduce the number of
      infiltrating leukocytes, predominately polymorphonuclear neutrophils (PMNs)
      determined by myeloperoxidase immunoreactivity, or infiltration of CD3+
      lymphocytes. The pial vessel occlusion induced a significant upregulation of IL
      1beta expression; however, minocycline treatment did not significantly alter this
      upregulation of IL-1beta. In this study, we found minocycline facilitated the
      repopulation of the lesion by reactive astrocytes and therefore prevented
      cavitation; however, we could not identify the molecular signal.

PMID- 16647694
TI  - Regulation of expression of early growth response transcription factors in rat
      primary cortical neurons by extracellular ATP.
AB  - The zinc finger transcription factor early growth response-1 (Egr-1, NGFI-A,
      zif268, Krox 24, TIS8, ZENK) is upregulated immediately in the brain by cortical
      spreading depression (CSD) and other preconditioning stimuli and thus might
      participate in regulation of the overall genomic response to preconditioning. In
      the present study, the induction of expression of Egr-1 and other early growth
      response family members was characterized in rat primary cortical neuronal
      cultures. In neuronal cultures in vitro, depolarization or exposure to
      extracellular glutamate caused a 4-fold increase in egr-1 mRNA while exposure to
      extracellular ATP caused a 10-fold increase. The presence of mRNA encoding for
      multiple types of purinergic receptors was confirmed by RT-PCR. A number of
      nucleotide agonists proved effective in eliciting an increase in egr-1 mRNA. Over
      a limited range of concentration, the most effective agonists were ATP > ADP >
      alpha, beta-methylene ATP > UTP > cAMP > UDP > AMP > adenosine. Pertussis toxin,
      suramin, reactive blue 2, PPADS, DPCPX and inhibitors of Protein Kinase C,
      Protein Kinase A and PI3 kinase significantly reduced the upregulation of egr-1
      by exposure to extracellular ATP. These findings suggest that neuronal
      metabotropic purinergic receptor activation contributes to the induction of early
      growth response transcription factors and may provide a target that can be
      manipulated to increase ischemic tolerance of the brain in vivo.

PMID- 16647695
TI  - Ho15J: a new hotfoot allele in a hot spot in the gene encoding the delta2
      glutamate receptor.
AB  - Hotfoot, a recessive mouse mutation characterized by ataxia and jerky movements
      of the hindlimbs, is caused by various mutations in the gene (Grid2) encoding the
      delta2 glutamate receptor (GluRdelta2). So far, at least 20 alleles, arising
      either spontaneously or through the random insertion of transgenes, have been
      described. Interestingly, most hotfoot mutants have deletions of one or more
      exons coding for portions of the most amino-terminal domain of GluRdelta2.
      However, because live mice colonies are no longer available for most hotfoot
      mutants, the possibility that the loss of a part of an intron might affect the
      splicing of other exons or the general efficiency of transcription could not be
      ruled out. Here, we report that a newly identified hotfoot mutant, ho15J, was
      caused by an intragenic deletion of the Grid2 gene, which indeed resulted in a
      new type of 52-amino-acid deletion in the most amino-terminal domain of
      GluRdelta2. Like GluRdelta2 proteins in ho4J mutants, GluRdelta2 proteins in
      ho15J mice were retained in the soma of Purkinje cells, where they were degraded.
      Long-term depression, a form of synaptic plasticity underlying information
      storage in the cerebellum, was abrogated, and ho15J mice showed severe motor
      discoordination on rotarod tests. The agreement between the PCR results for
      genomic DNA and the RT-PCR results for the ho15J allele supports the view that
      PCR analyses of grid2 genomic DNA can predict alterations in mRNA and protein. In
      addition, the present findings underscore the importance of the most amino
      terminal domain in GluRdelta2 signaling and cerebellar functions.

PMID- 16647696
TI  - Cancer risk assessment for 1,3-butadiene: data integration opportunities.
AB  - The US Environmental Protection Agency recently released its new guidelines for
      carcinogen risk assessment together with supplemental guidance for assessing
      susceptibility from early-life exposure to carcinogens. In particular, these
      guidelines encourage the use of mechanistic data in support of dose-response
      characterization at doses below those at which an increase in tumor frequency
      over background levels might be detected. In this context of the utility of
      mechanistic data for human cancer risk assessment, the International Life
      Sciences Institute (ILSI) has developed a human relevance framework (HRF) that
      can be used to assess the plausibility of a mode of action (MoA) described for
      animal models operating in humans. The MoA is described as a sequence of key
      events and processes that result in an adverse outcome. A key event is a
      measurable precursor step that is in itself a necessary element of the MoA or is
      a bioindicator for such an element. A number of cellular and molecular
      perturbations have been identified as key events whereby DNA-reactive chemicals
      can produce tumors. These include DNA adducts in target tissues, gene mutations
      and/or chromosomal alterations in target tissues and enhanced cell proliferation
      in target tissues. This type of data integration approach to quantitative cancer
      risk assessment can be applied to 1,3-butadiene, for example, using data on
      biomarkers in exposed Czech workers [1]. For this study, an extensive range of
      biomarkers of exposure and response was assessed, including: polymorphisms in
      metabolizing enzymes; urinary concentrations of several metabolites of 1,3
      butadiene; hemoglobin adducts; HPRT mutations in T-lymphocytes; chromosomal
      aberrations by FISH and conventional staining procedures; sister chromatid
      exchanges. Exposure levels were monitored in a comprehensive fashion. For risk
      assessment purposes, these data need to be considered in the context of how they
      inform the MoA for leukemia, the tumor type reported to be increased in synthetic
      rubber workers exposed to 1,3-butadiene. Also, for the HRF it is necessary to
      establish key events for a MoA in rodents for the induction of tumors by 1,3
      butadiene. There is clearly a species difference in sensitivity to tumor
      induction, with mice being much more sensitive than rats; key events need to
      explain this difference. For butadiene, the MoA is DNA-reactivity and subsequent
      mutagenicity and so following the EPA's cancer guidelines, a linear extrapolation
      is used from the point of departure (POD), unless additional data support a non
      linear extrapolation. For the present case, the human bioindicator data are not
      informative as far as dose-response characterization is concerned. Mouse
      chromosome aberration data for in vivo exposures might be used for establishing a
      POD, with linear extrapolation from this POD. The available cytogenetic data from
      rodent studies appear to be sufficiently extensive and consistent for this to be
      a viable approach. This approach of using MoA and key events to establish the
      human relevance can lead to the development of specific informative bioindicators
      of response that can be used as surrogates to predict the shape of the tumor dose
      response curve at low doses. Truly informative predictors of tumor responses
      should be able to provide estimates of human tumor frequencies at low,
      environmental exposures to 1,3-butadiene.

PMID- 16647697
TI  - Liquiritigenin, an aglycone of liquiritin in Glycyrrhizae radix, prevents acute
      liver injuries in rats induced by acetaminophen with or without buthionine
      sulfoximine.
AB  - Glycyrrhizae radix has been used as one of the oldest and most frequently
      employed botanicals in both western and oriental countries. Previously, we showed
      that liquiritigenin (LQ), an aglycone of liquiritin in G. radix, exerts
      cytoprotective effects against heavy metal-induced toxicity in vitro. This study
      investigated in vivo protective effects of LQ against acute liver injuries
      induced by acetaminophen (APAP) or APAP plus buthionine sulfoximine (BSO). Liver
      injuries were assessed by blood biochemistry and histopathology in rats
      administered with LQ purified from the acid hydrolyates of liquiritin singly
      (p.o. or i.v., 2-4 days) or in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'
      dimethylenedioxybiphenyl-2,2'-dicarboxylate (DDB), a synthetic derivative of
      Schisandrin C in Fructus shizandrae, and exposed to APAP or APAP + BSO. LQ
      treatments (oral) effectively decreased liver injuries induced by a single dose
      of APAP, as evidenced by decreases in hepatic necrosis and inflammation as well
      as plasma alanine aminotransferase and lactate dehydrogenase activities. LQ, when
      intravenously applied, enhanced hepatoprotective effect with a greater potency.
      APAP + BSO led to severe liver injuries, resulting in lethality. LQ pretreatments
      significantly reduced the potentiated liver necrosis, decreasing mortality. In
      spite of the improvement in blood biochemistry, DDB failed to protect the liver
      from injuries induced by APAP or APAP + BSO. Combined treatments of rats with LQ
      and DDB showed some additive protective effect. The present study demonstrates
      that LQ efficaciously protects the liver from acute injuries induced by APAP or
      from APAP-induced severe injuries during GSH deficiency, indicating that LQ is
      one of the principal cytoprotective components comprised in G. radix.

PMID- 16647698
TI  - Galactose oxidase action on galactose containing glycolipids--a fluorescence
      method.
AB  - Features that alter the glycolipid sugar headgroup accessibility at the membrane
      interface have been studied in bilayer lipid model vesicles using a fluorescence
      technique with the enzyme galactose oxidase. The effects on oxidation caused by
      variation in the hydrophobic moiety of galactosylceramide or the membrane
      environment for galactosylceramide, monogalactosyldiacylglycerol and
      digalactosyldiacylglycerol were studied. For this study we combined the galactose
      oxidase method for determining the oxidizability of galactose containing
      glycolipids, and the fluorescence method for determining enzymatic hydrogen
      peroxide production. Exposed galactose residues with a free hydroxymethyl group
      at position 6 in the headgroup of glycolipids were oxidized with galactose
      oxidase and subsequently the resultant hydrogen peroxide was determined by a
      combination of horseradish peroxidase and 10-acetyl-3,7-dihydroxyphenoxazine
      (Amplex Red). Amplex Red reacts with hydrogen peroxide in the presence of
      horseradish peroxidase with a 1:1 stoichiometry to form resorufin. With this
      coupled enzyme approach it is also possible to determine the galactolipid
      transbilayer membrane distribution (inside-outside) in bilayer vesicles.

PMID- 16647699
TI  - Evaluation of clinical and biochemical parameters in hepatocellular carcinoma:
      experience from an Indian center.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy
      of the liver. Several etiologic factors including hepatitis viruses, alcohol and
      aflatoxin have been implicated in the pathogenesis of HCC. However, there is
      limited information regarding clinicopathological profile of HCC from the Indian
      subcontinent. METHODS: Forty seven patients of HCC (M=43, F=4) diagnosed on the
      basis of history, clinical examination, imaging (USG, CT/MRI), alpha-fetoprotein
      (AFP) and by USG/CT guided FNAC, were included. Patients were screened for HBV,
      HCV and history of alcohol. Tumor size was assessed on imaging and UGI endoscopy
      for the presence of varices. RESULTS: The mean age was 53.4+/-14.6 y. Clinical
      presentation included anorexia in 32 (68%), abdominal pain in 28 (60%), loss of
      weight in 23 (49%), fever in 12 (26%), and jaundice in 6 (13%) patients. Twenty
      nine (62%) had underlying cirrhosis, diagnosed by ultrasound or CT. Seventeen
      percent had normal AFP (<10 ng/ml) and the remaining 83% had raised AFP [<10
      ng/ml=7, 10-400 ng/ml=27, >400 ng/ml=8]. Thirteen patients (28%) were consuming
      alcohol in cirrhogenic doses and 10 (21%) were smokers. Fifty four percent were
      positive for HBsAg, 47% of these were also positive for HBeAg. Twenty seven
      percent were positive for anti-HCV. Tumor size on imaging was analyzed in 33
      patients. Tumor size varied from <3 cm in 8 (18%), 3-5 cm in 12 (27%) and >5 cm
      in 25 (56%) patients. Twenty-three patients were lost to follow-up, 4 died and 6
      did not agree for any treatment. Only 5 patients could be subjected to hepatic
      resection. Remaining 9 patients had a large tumor size and were put on tamoxifen.
      CONCLUSION: More than half of the HCC cases have underlying cirrhosis. Hepatitis
      B virus infection is commonly associated. Most of patients have a large tumor (>5
      cm) at presentation.

PMID- 16647700
TI  - Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte
      stimulating hormone for long-lasting protection against ischemic stroke, in
      Mongolian gerbils.
AB  - Melanocortin peptides have been shown to produce neuroprotection in experimental
      ischemic stroke. The aim of the present investigation was to identify the
      therapeutic treatment window of melanocortins, and to determine whether these
      neuropeptides chronically protect against damage consequent to brain ischemia. A
      10-min period of global cerebral ischemia in gerbils, induced by occluding both
      common carotid arteries, caused impairment in spatial learning and memory (Morris
      test: four sessions from 4 to 67 days after the ischemic episode), associated
      with neuronal death in the hippocampus. Treatment with a nanomolar dose (340
      microg/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D
      Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h
      after the ischemic episode, reduced hippocampal damage with improvement in
      subsequent functional recovery. The protective effect was long-lasting (67 days,
      at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest
      treated (18 h) gerbils, some spatial memory deficits were detected.
      Pharmacological blockade of melanocortin MC(4) receptors prevented the protective
      effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain
      ischemia, melanocortins can provide strong and long-lasting protection with a
      broad therapeutic treatment window, and with involvement of melanocortin MC(4)
      receptors, 18 h being the approximately time-limit for stroke late treatment to
      be effective.

PMID- 16647701
TI  - Discriminative stimulus effects of GHB and GABA(B) agonists are differentially
      attenuated by CGP35348.
AB  - The aim of this study was to examine the possible heterogeneity of mechanisms
      that contribute to the discriminative stimulus and rate-decreasing effects of
      gamma-hydroxybutyrate (GHB). Dose effect curves were determined for GHB and two
      GABA(B) receptor agonists (baclofen and SKF97541) alone and together with the
      selective GABA(B) receptor antagonist CGP35348 in rats discriminating GHB. In a
      second study, GHB and SKF97541 dose effect curves were determined alone and
      together with baclofen. CGP35348 attenuated the discriminative stimulus and rate
      decreasing effects of SKF97541 and baclofen to a greater extent than those of
      GHB. In the second study, baclofen enhanced the discriminative stimulus and rate
      decreasing effects of GHB and SKF97541; however, the GHB dose effect curve was
      not shifted in a parallel manner. Taken together, these data suggest that
      multiple mechanisms, possibly including GHB receptors and GABA(B) receptor
      subtypes, are involved in the discriminative stimulus and rate-decreasing effects
      of GHB.

PMID- 16647702
TI  - Long-term facilitation of ipsilateral but not contralateral phrenic output after
      cervical spinal cord hemisection.
AB  - After chronic C2 spinal hemisection (C2HS), exposure to intermittent hypoxia (IH)
      evokes a persistent increase in phrenic output recorded ipsilateral to the injury
      (i.e., phrenic long-term facilitation, LTF; Golder and Mitchell, J. Neurosci.
      25:2925-32, 2005). However, unilateral spinal cord injury induces compensatory
      increases in contralateral motoneuron activity that may reduce their capacity for
      further plasticity (i.e., a "ceiling effect"). We hypothesized that after chronic
      C2HS, LTF would be reduced in contralateral (vs. ipsilateral) phrenic output.
      Bilateral phrenic activity was recorded in three groups of anesthetized,
      paralyzed, vagotomized, and ventilated rats: uninjured, and 4 or 8 weeks
      following histologically verified C2HS. Baseline (BL) phrenic activity was
      established during normoxia and rats were then exposed to IH (5 x 3 min isocapnic
      hypoxia, 13-14% O2) followed by isocapnic normoxia; LTF was assessed 60-min post
      IH. Uninjured animals showed an increase in inspiratory burst amplitude that was
      similar in the left (44 +/- 11%BL) and right phrenic nerves (39 +/- 13%BL).
      However, similar burst amplitude LTF did not occur in phrenic output recorded
      contralateral to C2HS at 4 (-10 +/- 7% BL) or 8 weeks post-C2HS (4 +/- 5% BL). In
      contrast, LTF of ipsilateral phrenic amplitude occurred at both 4 (44 +/- 11% BL)
      and 8 weeks post-C2HS (129 +/- 30% BL, P < 0.05). A persistent increase in
      phrenic burst frequency after IH (i.e., "frequency LTF") was observed in control
      (+9 +/- 3 burst/min, P < 0.05), but not C2HS rats. We conclude that compensatory
      responses to unilateral cervical spinal cord injury prevent the expression of LTF
      in contralateral phrenic motoneurons.

PMID- 16647703
TI  - Inhibition of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      endocytosis by ouabain in human endothelial cells.
AB  - 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake and
      reduction is widely used to evaluate cell proliferation and viability. MTT is
      taken up by the cells through endocytosis. We find that ouabain (1-200 nM)
      inhibits MTT reduction in human umbilical vein endothelial cells (HUVEC) without
      affecting cell viability. Ouabain does not inhibit MTT reduction when cell
      lysates substituted for the intact cells. Disruption of caveolae by cholesterol
      depletion, completely prevents the effect of ouabain. Treatment of HUVEC with Src
      inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine
      partially abrogates the inhibitory effect of ouabain. The data suggest that
      ouabain interaction with caveolar Na/K-ATPase inhibits MTT endocytosis through
      the activation of signaling proteins such as Src kinase.

PMID- 16647704
TI  - MELDB: a database for microbial esterases and lipases.
AB  - MELDB is a comprehensive protein database of microbial esterases and lipases
      which are hydrolytic enzymes important in the modern industry. Proteins in MELDB
      are clustered into groups according to their sequence similarities based on a
      local pairwise alignment algorithm and a graph clustering algorithm (TribeMCL).
      This differs from traditional approaches that use global pairwise alignment and
      joining methods. Our procedure was able to reduce the noise caused by dubious
      alignment in the distantly related or unrelated regions in the sequences. In the
      database, 883 esterase and lipase sequences derived from microbial sources are
      deposited and conserved parts of each protein are identified. HMM profiles of
      each cluster were generated to classify unknown sequences. Contents of the
      database can be keyword-searched and query sequences can be aligned to sequence
      profiles and sequences themselves.

PMID- 16647705
TI  - Hexapeptides that interfere with HIV-1 fusion peptide activity in liposomes block
      GP41-mediated membrane fusion.
AB  - Upon receptor-mediated activation, the gp41 hydrophobic, conserved fusion peptide
      inserts into the target membrane and promotes the kind of perturbations required
      for the progression of the HIV-cell fusion reaction. Using a synthetic
      combinatorial library we have identified all d-amino acid hexapeptide sequences
      that inhibited the fusion peptide capacity of perturbing model membranes. Two
      hexapeptides that effectively inhibited the fusion peptide in these systems were
      subsequently shown to inhibit cell-cell fusion promoted by gp41 expressed at cell
      surfaces. These observations might be of importance for understanding the
      mechanisms underlying fusion peptide activity and suggest new strategies for
      screening compounds that target these viral sequences.

PMID- 16647706
TI  - Ubiquinone (coenzyme Q10) binding sites: low dielectric constant of the gate
      prevents the escape of the semiquinone.
AB  - The photosynthetic reaction center (RC) from purple bacteria is frequently used
      as a model for the interaction of ubiquinones (coenzyme Q) with membrane
      proteins. Single-turnover flash activation of RC leads to formation of the
      semiquinone (SQ) of the secondary acceptor quinone after odd flashes and quinol
      after even flashes. The ubiquinol escapes the binding site in 1 ms, while the SQ
      does not leave the binding site for at least 5 min. Observed difference between
      these times suggests a large energetic barrier for the SQ. However, high apparent
      dielectric constant in the vicinity of the quinone ring (>or=25) results in a
      relatively small electrostatic energy of SQ stabilization. To resolve this
      apparent contradiction I suggest that a significant part of the kinetic
      stabilization of the SQ is achieved by the special topology of the binding site
      in which quinone can exit the binding site only by moving its headgroup toward
      the center of the membrane. The large energetic penalty of transferring the
      charged headgroup to the membrane dielectric can explain the observed kinetic
      stability of the SQ.

PMID- 16647707
TI  - A translational enhancer element on the 3'-proximal end of the Panicum mosaic
      virus genome.
AB  - Panicum mosaic virus (PMV) is a single-stranded positive-sense RNA virus in the
      family Tombusviridae. PMV genomic RNA (gRNA) and subgenomic RNA (sgRNA) are not
      capped or polyadenylated. We have determined that PMV uses a cap-independent
      mechanism of translation. A 116-nucleotide translational enhancer (TE) region on
      the 3'-untranslated region of both the gRNA and sgRNA has been identified. The TE
      is required for efficient translation of viral proteins in vitro. For mutants
      with a compromised TE, addition of cap analog, or transposition of the cis-active
      TE to another location, both restored translational competence of the 5'-proximal
      sgRNA genes in vitro.

PMID- 16647708
TI  - Cellular coexistence of two high molecular subsets of eEF1B complex.
AB  - The elongation factor eEF1B involved in protein translation was found to contain
      two isoforms of the eEF1Bdelta subunit in sea urchin eggs. The eEF1Bdelta2
      isoform differs from eEF1Bdelta1 by a specific insert of 26 amino acids. Both
      isoforms are co-expressed in the cell and likely originate from a unique gene.
      The feature appears universal in metazoans as judged from in silico analysis in
      EST-databanks. The eEF1B components were co-immunoprecipitated by specific
      eEF1Bdelta2 antibodies. Quantification of the proteins in immunoprecipitates and
      on immunoblots demonstrates that eEF1Bdelta1 and eEF1Bdelta2 proteins are present
      in two subsets of eEF1B complex. We discuss and propose a model for the different
      subsets of eEF1B complex concomitantly present in the cell.

PMID- 16647709
TI  - Inhibition of vacuolar-type (H+)-ATPase by the cytostatic macrolide apicularen A
      and its role in apicularen A-induced apoptosis in RAW 264.7 cells.
AB  - Apicularen A and the known vacuolar-type (H(+))-ATPase (V-ATPase) inhibitor
      bafilomycin A(1) induced apoptosis of RAW 264.7 cells, while apicularen B, an N
      acetyl-glucosamine glycoside of apicularen A, was far less effective. Apicularen
      A inhibited vital staining with acridine orange of the intracellular organelles
      of RAW 264.7 cells, inhibited the ATP-dependent proton transport into inside-out
      microsome vesicles, and inhibited the bafilomycin A(1)-sensitive ATP hydrolysis.
      The IC(50) values of the proton transport were 0.58 nM for apicularen A, 13 nM
      for apicularen B, and 0.95 nM for bafilomycin A(1). Furthermore, apicularen A
      inhibited the bafilomycin A(1)-sensitive ATP hydrolysis more potently than
      apicularen B. F-ATPase and P-ATPase were not inhibited by apicularen A. We
      concluded that apicularen A inhibits V-ATPase, and thus induces apoptosis in RAW
      264.7 cells.

PMID- 16647710
TI  - Mitral annular calcification predicts mortality and coronary artery disease in
      end stage renal disease.
AB  - BACKGROUND: We sought to determine whether mitral annular calcification (MAC)
      predicts mortality and cardiac disease in a group of renal transplant candidates.
      METHODS: Hundred and forty patients were prospectively studied. All had
      echocardiography and coronary angiography. Significant coronary artery disease
      (CAD) was defined as luminal stenosis >70% by visual estimation in at least one
      coronary artery. RESULTS: There were 21 deaths over a follow-up period of 2.2+/
      0.7 years. MAC occurred in 56 patients (40%) and was associated with higher
      mortality (p=0.04). Patients with MAC were older (p=or<0.001), had larger left
      ventricular (LV) end systolic (p=0.005) and LV end diastolic (p=0.04) diameter,
      larger left atrial diameter (p=0.001), lower LV fractional shortening (p=0.003),
      larger LV mass index (p=0.04) and higher mitral E/Ea ratio (p=0.03) compared to
      those without. Plasma calcium (p=0.002), phosphate (p=0.004), cardiac troponin T
      (p=0.03), N-terminal Pro-B-type natriuretic peptide (p=0.004) concentrations were
      higher in those with MAC but gender, total cholesterol, haemoglobin and
      creatinine were similar in the two groups. The proportion diabetic (p=0.03), on
      dialysis (p=0.05), with significant CAD (p=or<0.001), taking calcium containing
      phosphate binders (p=0.02) and Vitamin D3 (p=0.04) was significantly higher in
      those with MAC. Significant CAD (OR 12, 95% CI 3.25, p=0.001) was the only
      independent associate of MAC. CONCLUSIONS: MAC is associated with increased
      mortality and significant CAD in ESRD. These patients have increased LV cavity
      size, poorer LV systolic function, higher LV filling pressures compared to
      patients without MAC.

PMID- 16647711
TI  - A thermodynamic study to evidence the alpha,omega-dichloroalkane/ block copolymer
      mixed aggregates formation: effect of the copolymer architecture.
AB  - The thermodynamics of alpha,omega-dichloroalkanes in aqueous solutions of
      (ethylene oxide)(11)(propylene oxide)(16)(ethylene oxide)(11) (L35) and
      (propylene oxide)(8)(ethylene oxide)(23)(propylene oxide)(8) (10R5) was
      determined at 298 and 305 K. Modeling the experimental data allowed to calculate
      the standard free energy (DeltaG(D)(o)/w) and the volume (DeltaV(D)/w) for the
      additive-copolymer mixed aggregates formation per additive molecule.
      DeltaG(D)(o)/w for Cl(2)CH(2) and Cl(2)(CH(2))(2) evidenced that the process is
      controlled by the forces exercising between the chlorine atoms and the OH groups
      of the copolymer micelles protruded into the aqueous phase. Cl(2)(CH(2))(3)
      experiences both the hydrophilic and hydrophobic domains into the aggregates. The
      hydrophobic interactions are more significant in 10R5 whereas the hydrophilic
      ones are more significant in L35. Temperature increase does not influence
      DeltaG(D)(o)/w in 10R5, whereas, it does influence DeltaG(D)(o)/w in L35,
      enhancing the ability of the aggregate to extract the chlorinated compounds from
      the aqueous phase. The DeltaV(D)/w values are consistent with the free energy
      results. These insights agree with those predicted by the Flory liquid lattice
      theory. The calculations extended to several alpha,omega-dichloroalkanes showed
      that Cl(2)CH(2) and Cl(2)(CH(2))(2) prefer poly(ethylene oxide) (PEO),
      Cl(2)(CH(2))(3) exhibits the same affinity for both PEO and poly(propylene oxide)
      (PPO), whereas the more hydrophobic additives show a preference for PPO. The
      copolymer architecture plays a relevant role in the alpha,omega-dichloroalkane
      solubilization into the polymeric aggregates.

PMID- 16647712
TI  - A modified alpha-galactosyl ceramide for staining and stimulating natural killer
      T cells.
AB  - CD1d presentation of alpha-galactosyl ceramides to natural killer T cells has
      been a focal point of the study of regulatory T cells. KRN7000, an alpha
      galactosyl ceramide originally generated from structure activity studies of
      antitumor properties of marine sponge glycolipids, is currently the most commonly
      used agonist ligand and is used to stain NKT cells. However, this glycolipid
      suffers from poor solubility and availability. We have developed an alpha
      galactosyl ceramide with improved solubility over KRN7000 that effectively stains
      NKT cells, both mouse and human, and stimulates cytokine release at low
      concentrations.

PMID- 16647713
TI  - Optimization of culture and storage conditions for an in vitro system to evaluate
      thymocyte phenotype and function.
AB  - Studies on thymopoiesis are critical to the understanding of T-cell homeostasis
      as well as the host response to T-cell depletion. Various in vitro culture
      systems have been used in the study of thymocyte development; however it is
      unclear if current co-culture methods have been fully optimized. In this study in
      vitro suspension cultures have been re-evaluated and the optimal storage
      conditions for thymocytes have been established by evaluating various methods of
      storing/isolating thymic tissue and isolated thymocytes as well as the source of
      thymic epithelial cells (TEC). It was determined that thymocytes must be freshly
      isolated from whole thymic tissue and ideally stored at 4 degrees C prior to co
      culture. Co-culture with either autologous or allogeneic TEC results in similar
      thymocyte subset distribution as well as interleukin-7 receptor-alpha (CD127)
      expression on these subsets. To evaluate the influence of the source of TEC on
      one aspect of thymocyte function the effect of IL-7 stimulation on the expression
      of CD127 was evaluated. IL-7 stimulation resulted in a downregulation of the
      expression of CD127 on all thymic subsets similar to that observed in circulating
      CD8+ T-cells. The effect of this was the same whether TEC were autologous or
      allogeneic. Optimizing culture techniques and facilitating the study of
      individual thymocyte subsets will lead to a better understanding of thymic
      function and development. It could also lead to therapeutic approaches that
      enhance immune recovery after T-cell depletion in HIV infection, bone marrow
      transplantation or following chemotherapy.

PMID- 16647714
TI  - Binding of TmHU to single dsDNA as observed by optical tweezers.
AB  - Optical tweezers are employed to study the action of the histone-like protein
      from Thermotoga maritima (TmHU) on DNA at a single molecule level. Binding and
      disruption of TmHU to and from DNA are found to take place in discrete steps of 4
      5 nm length and a net binding enthalpy of about 16kBT. This is in reasonable
      agreement with a microscopic model that estimates the extension of the binding
      sites of the protein and evaluates the energetics mainly for bending of the DNA
      in the course of interaction.

PMID- 16647715
TI  - A universal type IA topoisomerase fold.
AB  - A class of enzymes, called DNA topoisomerases, is responsible for controlling the
      topological state of cellular DNA. Among these, type IA topoisomerases form a
      vast family that is present in all living organisms, including higher eukaryotes,
      in which they play important roles in genome stability. The known 3D structures
      of three of these enzymes indicate that they share a common toroidal
      architecture. We previously showed that the toroidal structure could be split off
      from the core enzyme of Thermotoga maritima topoisomerase I by limited
      proteolysis. This structure is produced by the association of two tandemly
      repeated elementary folds in a head-to-tail orientation. By using a combination
      of structural and sequence data analysis, we show that the elementary fold of
      about 150 amino acid residues, referred to as the topofold, is likely to be
      present in the whole topoisomerase IA family. Within each enzyme, the successive
      topofolds share two conserved sequence motifs located at the base of the ring,
      and referred to as the MI and MII motifs. However, the overall sequences of the
      folds have largely diverged. By contrast, secondary and tertiary structures
      appear remarkably conserved. We suggest that this twofold repeat has evolved by
      gene duplication/fusion from an ancestral topofold.

PMID- 16647716
TI  - Crystal structure of yeast mitochondrial peripheral membrane protein Tim44p C
      terminal domain.
AB  - The protein transports from the cell cytosol to the mitochondria matrix are
      carried out by the translocase of the outer membrane (TOM) complex and the
      translocase of the inner membrane (TIM) complexes. Tim44p is an essential
      mitochondrial peripheral membrane protein and a major component of TIM23
      translocon. Tim44p can tightly associate with the inner mitochondrial membrane.
      To investigate the mechanism by which Tim44p functions in the TIM23 translocon to
      deliver the mitochondrial protein precursors, we have determined the crystal
      structure of the yeast Tim44p C-terminal domain to 3.2A resolution using the MAD
      method. The Tim44p C-terminal domain forms a monomer in the crystal structure and
      contains six alpha-helices and four antiparallel beta-strands. A large
      hydrophobic pocket was identified on the Tim44p structure surface. The N-terminal
      helix A1 is positively charged and the helix A1 protrudes out from the Tim44p
      main body.

PMID- 16647717
TI  - Crystallographic and pre-steady-state kinetics studies on binding of NADH to wild
      type and isoniazid-resistant enoyl-ACP(CoA) reductase enzymes from Mycobacterium
      tuberculosis.
AB  - An understanding of isoniazid (INH) drug resistance mechanism in Mycobacterium
      tuberculosis should provide significant insight for the development of newer anti
      tubercular agents able to control INH-resistant tuberculosis (TB). The inhA
      encoded 2-trans enoyl-acyl carrier protein reductase enzyme (InhA) has been shown
      through biochemical and genetic studies to be the primary target for INH. In
      agreement with these results, mutations in the inhA structural gene have been
      found in INH-resistant clinical isolates of M.tuberculosis, the causative agent
      of TB. In addition, the InhA mutants were shown to have higher dissociation
      constant values for NADH and lower values for the apparent first-order rate
      constant for INH inactivation as compared to wild-type InhA. Here, in trying to
      identify structural changes between wild-type and INH-resistant InhA enzymes, we
      have solved the crystal structures of wild-type and of S94A, I47T and I21V InhA
      proteins in complex with NADH to resolutions of, respectively, 2.3A, 2.2A, 2.0 A,
      and 1.9A. The more prominent structural differences are located in, and appear to
      indirectly affect, the dinucleotide binding loop structure. Moreover, studies on
      pre-steady-state kinetics of NADH binding have been carried out. The results
      showed that the limiting rate constant values for NADH dissociation from the InhA
      NADH binary complexes (k(off)) were eleven, five, and tenfold higher for,
      respectively, I21V, I47T, and S94A INH-resistant mutants of InhA as compared to
      INH-sensitive wild-type InhA. Accordingly, these results are proposed to be able
      to account for the reduction in affinity for NADH for the INH-resistant InhA
      enzymes.

PMID- 16647718
TI  - Do proteins with similar folds have similar transition state structures? A
      diffuse transition state of the 169 residue apoflavodoxin.
AB  - Apoflavodoxin from Anabaena PCC 7119 is a 169 residue globular protein of known
      structure and energetics. Here, we present a comprehensive Phi-value analysis to
      characterize the structure of its transition state. A total of 34 non-disruptive
      mutations are made throughout the structure and a range of Phi-values from zero
      to one are observed. In addition, a small set of eight aliphatic small-to-large
      mutations have been introduced in the hydrophobic core of the protein and they
      have been analyzed to investigate the feasibility of stabilizing the unfolding
      transition state by creating new non-native interactions. We find that the
      transition state of apoflavodoxin (so far the largest protein subjected to Phi
      analysis) is diffuse and that it can be stabilized by unspecific hydrophobic
      interactions that can speed up the folding reaction. The data gathered on the
      apoflavodoxin transition state are compared with results from experimental
      studies in other proteins to revisit the relationship between the native state
      topology and transition state structure.

PMID- 16647719
TI  - Structures of ubiquitin insertion mutants support site-specific reflex response
      to insertions hypothesis.
AB  - We previously concluded that, judging from NMR chemical shifts, the effects of
      insertions into ubiquitin on its conformation appear to depend primarily on the
      site of insertion rather than the sequence of the insertion. To obtain a more
      complete and atomic-resolution understanding of how these insertions modulate the
      conformation of ubiquitin, we have solved the crystal structures of four
      insertional mutants of ubiquitin. Insertions between residues 9 and 10 of
      ubiquitin are minimally perturbing to the remainder of the protein, while larger
      alterations occur when the insertion is between residues 35 and 36. Further, the
      alterations in response to insertions are very similar for each mutant at a given
      site. Two insertions, one at each site, were designed from structurally
      homologous proteins. Interestingly, the secondary structure within these five to
      seven amino acid residue insertions is conserved in the new protein. Overall, the
      crystal structures support the previous conclusion that the conformational
      effects of these insertions are determined largely by the site of insertion and
      only secondarily by the sequence of the insert.

PMID- 16647720
TI  - Risky behavior of drivers of motorized two wheeled vehicles in India.
AB  - INTRODUCTION: Motorized two-wheeled vehicles (MTV) account for a large proportion
      of road traffic in India and the riders of these vehicles have a high risk of
      road traffic injuries. We report on the availability of drivers licenses, use of
      a helmet, driver behavior, and condition of vehicles for MTV drivers in
      Hyderabad, a city in India METHODS: Drivers of a MTV aged >16 years were
      interviewed at petrol filling stations RESULTS: There were 4,183 MTV drivers who
      participated in the study. Four hundred sixty one (11%; 95% CI 9.7-12.3%) drivers
      had not obtained a drivers license and 798 (21.4%) had obtained a license without
      taking the mandatory driving test. Two thousand nine hundred twenty (69.8%; 95%
      CI 67.9-71.7%) drivers reported no/very occasional use of a helmet, the
      significant predictors of which included that those driving borrowed a MTV (odds
      ratio 7.90; 95% CI 3.40-18.40) or driving moped/scooterette/scooter as compared
      with motorcycle (3.32; 2.76-3.98), lower education (3.10; 2.66-3.61), age >45
      years (2.41; 1.63-3.57), and males (1.57; 1.16-2.13). Two thousand five hundred
      and eight (59.9%) drivers reported committing a traffic law violation at least
      once within the last 3 months. Overall, 1,222 (29.2%) drivers reported ever being
      caught by traffic police for a traffic law violation with data on violations
      available for 1,205 of these drivers, of whom 680 (56.4%) paid a fine, 310
      (25.7%) paid by bribe, and 215 (17.8%) made no payment. The proportion of those
      who did not make payment for committed violation was significantly higher among
      females (46.8%) than males (16.3%). Two thousand fifty two (49%) of all MTVs had
      no rearview mirror CONCLUSIONS: These data suggest the need to enact and enforce
      policy interventions for improving the drivers license system, mandatory use of a
      helmet, effective traffic law enforcement, and ensuring good vehicle condition to
      reduce the risk factors that potentially contribute to mortality and morbidity in
      road traffic crashes in MTV drivers in Indian cities.

PMID- 16647721
TI  - Effects of chronic fluvoxamine on ethanol- and food-maintained behaviors.
AB  - Acute treatment with fluvoxamine reduces responding for ethanol more than
      responding for food. However, pharmacotherapy for alcoholism is likely to require
      chronic treatment. These experiments were performed to assess the effects of
      chronic fluvoxamine on ethanol- and food-maintained behaviors. Effects of chronic
      fluvoxamine (10 and 17.8 mg/kg/dayx30 days) on ethanol- and food-maintained
      responding were compared to responding during saline treatment in four Sprague
      Dawley rats responding for ethanol and food under a multiple fixed-ratio 5, fixed
      ratio 5 schedule. In two subjects, chronic fluvoxamine reduced ethanol-maintained
      responding more than food-maintained responding; however this effect was
      transient. In another subject, treatment persistently decreased food-maintained
      responding relative to ethanol-maintained responding. Finally, in one subject,
      fluvoxamine nonspecifically disrupted responding for food and ethanol. Similar to
      results in humans, outbred Sprague-Dawley rats had differential responses to
      chronic fluvoxamine. The effect was transient in rats that responded favorably
      (greater reduction of ethanol relative to food responding), while response
      reductions persisted throughout treatment in rats that responded unfavorably
      (greater reduction of food relative to ethanol or nonspecific reductions).

PMID- 16647722
TI  - Effect of estrogen on calcium-handling proteins, beta-adrenergic receptors, and
      function in rat heart.
AB  - Regulation of cellular Ca(2+) cycling is central to myocardial contractile
      function. Loss of Ca(2+) regulation is associated with cardiac dysfunction and
      pathology. Estrogen has been shown to modify contractile function and to confer
      cardioprotection. Therefore, we investigated the effect of estrogen on expression
      of rat heart myocardial Ca(2+)-handling proteins and beta-adrenergic receptor
      (beta(1)-AR) and examined functional correlates. Female rats were sham-operated
      (SHAM) or ovariectomized. Two weeks after ovariectomy rats were injected (i.p.)
      daily with estradiol benozoate (OVX+EB) or sesame oil (OVX) for 2 weeks. Protein
      abundance was measured by immunoblotting and mRNA was quantified by real-time RT
      PCR. OVX significantly decreased estrogen and progesterone levels and EB
      replacement returned both estrogen and progesterone to physiological levels. OVX
      induced a 75% reduction of uterine weight and a gain in body weight. Replacement
      restored weights to SHAM level. OVX increased and estrogen-replacement normalized
      abundance of beta(1)-AR and L-type Ca(2+) channel (Cav1.2) protein. OVX decreased
      sodium-Ca(2+) exchange protein (NCX) and estrogen restored protein abundance to
      SHAM levels. Sarcoplasmic reticular ATPase (SERCA), phospholamban (PLB), and
      ryanodine receptor (RyR) abundance was not altered by hormone status. Levels of
      mRNA encoding for beta(1)-AR, Cav1.2, and NCX were not influenced by OVX or
      estrogen replacement. OVX had no effect on SERCA and PLB mRNA level but estrogen
      replacement elicited a significant increase compared to OVX and SHAM. Estrogen
      dependent changes in Ca(2+)-handling proteins and beta(1)-AR are theoretically
      consistent reduced myocellular Ca(2+) load. However, hormone-dependent
      alterations in protein were not associated with changes in contractile function.

PMID- 16647723
TI  - Antimutagenicity of ursolic acid and oleanolic acid against doxorubicin-induced
      clastogenesis in Balb/c mice.
AB  - Ursolic acid (UA) and oleanolic acid (OA) are triterpenoid compounds found in
      food, medicinal herbs and various other plants in free form or bound to
      glycosides. Both substances are known for their antimicrobial, hepatoprotective,
      anti-inflammatory, antiallergic, antiviral and cytotoxic activities. In the
      present study, we evaluated the antimutagenic potential of UA and OA using the
      micronucleus test in peripheral blood and bone marrow of Balb/c mice. The animals
      were divided into 10 treatment groups: mice treated with UA (80 mg/kg b.w.); OA
      (80 mg/kg b.w.); a mixture of UA and OA (80 mg/kg b.w.); the antineoplastic agent
      doxorubicin (DXR, 90 mg/kg b.w.); DMSO and DXR; UA and DXR; OA and DXR; UA, OA
      and DXR, and negative and solvent controls. UA, OA and a mixture of UA and OA
      were administered to the animals by gavage, followed by the intraperitoneal
      injection of DXR. The results showed a significant reduction in micronucleus
      frequency in the groups concomitantly treated with the triterpenoid compounds and
      DXR compared to that treated with DXR alone. The present results demonstrate the
      antimutagenic activity of UA and OA under the experimental conditions used in
      this study.

PMID- 16647724
TI  - Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme
      activities in C57BL/KsJ-db/db mice.
AB  - This study examines whether anti-diabetic effects of genistein and daidzein are
      mediated by hepatic glucose and lipid regulating enzyme activities in type 2
      diabetic animals. Male C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and age-matched
      non-diabetic littermates (db/+) were used in this study. The db/db mice were
      divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups.
      The blood glucose and HbA(1c) levels were significantly lower in the genistein
      and daidzein groups than in the control group, while glucose tolerance only was
      significantly improved in the genistein-supplemented group. The plasma insulin
      and C-peptide levels did not differ significantly between groups, yet the
      glucagon level was lower in the genistein and daidzein groups compared to that in
      the control db/db or db/+ group. The genistein and daidzein supplements increased
      the insulin/glucagon ratio in the type 2 diabetic animals. While the hepatic
      glucokinase activity was significantly lower in the db/db control group, the
      glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were
      significantly higher in the control group compared to the db/+ group.
      Interestingly, these hepatic glucose metabolizing enzyme activities were reversed
      by the genistein and daidzein supplementation in db/db mice compared to the
      control group. The hepatic fatty acid synthase, beta-oxidation and carnitine
      palmitoyltransferase activities were all significantly lower in the genistein and
      daidzein groups than in the control group. The genistein and daidzein supplements
      also improved the plasma total cholesterol, triglyceride, HDL-cholesterol/total
      cholesterol, free fatty acid and hepatic triglyceride concentrations in the db/db
      mice. These results suggest that genistein and daidzein exert anti-diabetic
      effect in type 2 diabetic conditions by enhancing the glucose and lipid
      metabolism.

PMID- 16647725
TI  - ICAM-1 expression and leukocyte behavior in the microcirculation of chronically
      ischemic rat skeletal muscles.
AB  - In muscle microcirculation, short periods of ischemia followed by reperfusion are
      known to upregulate leukocyte and endothelial adhesion molecules, but little is
      known about leukocyte adherence and ICAM-1 expression during chronic ischemia or
      any likely effect of muscle activity which is recommended in chronic ischemia due
      to peripheral arterial disease. Leukocyte rolling and stationary adhesion were
      observed in post-capillary venules in ischemic and contralateral rat extensor
      digitorum longus (EDL) muscles 3 and 7 days after unilateral ligation of the
      common iliac artery and in 3-day ischemic EDLs that were electrically stimulated
      on days 1 and 2 post-ligation (7 x 15 min per day). ICAM-1 was localized
      immunohistochemically to venular vessels in all muscles. Following ligation, use
      of the ischemic leg was observed to be restricted for the first 3 days, returning
      to normal by 7 days. After 3 days, leukocyte rolling/adherence and ICAM-1
      expression were no different in ischemic than control muscles, but all were
      increased in contralateral muscles. In ischemic muscles, electrical stimulation
      doubled the numbers of rolling leukocytes and upregulated ICAM-1 expression.
      After 7 days, increased muscle activity as a result of natural movement also
      resulted in greater ICAM-1 expression, a 4- to 5-fold increase in rolling
      leukocyte numbers and a 3-fold increase in stationary adherent leukocytes.
      Chronic ischemia thus increases ICAM-1 and leukocyte adherence in muscle
      microcirculation only when combined with contractile activity. Post-capillary
      venular endothelium may be modified by muscle acidosis when contractions are
      performed under low flow conditions or by changes in rheological (shear force)
      factors.

PMID- 16647726
TI  - Limbic and HPA axis function in an animal model of chronic neuropathic pain.
AB  - Chronic pain can be considered a form of chronic stress, and chronic pain
      patients often have disturbances of the hypothalamic-pituitary-adrenal (HPA)
      axis, including abnormal cortisol levels. In addition, chronic pain patients have
      an increased incidence of depression and anxiety, stress-related disorders that
      are frequently accompanied by disturbances in the limbic system (e.g. hippocampus
      and amygdala) and the HPA axis. Despite the fact that the literature supports a
      strong link between chronic pain, stress disorders, and limbic dysfunction, the
      mechanisms underlying the effects of chronic pain on the HPA axis and limbic
      system are not understood. The current study employs a rodent neuropathic pain
      model (chronic constriction injury (CCI) of the sciatic nerve) to assess the long
      term impact of chronic pain on the HPA axis and limbic system. Adult male rats
      received CCI or sham surgery; nociceptive behavioral testing confirmed CCI
      induced neuropathic pain. Tests of HPA axis function at 13-23 days postsurgery
      demonstrated that CCI did not affect indices of basal or restraint stress-induced
      HPA axis activity. CCI increased the expression of corticotrophin releasing
      hormone mRNA in the central amygdala, and not the paraventricular nucleus of the
      hypothalamus or the bed nucleus of the stria terminalis. Moreover, glucocorticoid
      receptor mRNA expression in CCI rats was increased in the medial and central
      amygdala, unaffected in the paraventricular nucleus, and decreased in the
      hippocampus. These results suggest that increased nociceptive sensitivity during
      chronic pain is associated with alterations in the limbic system, but is
      dissociated from HPA axis activation.

PMID- 16647727
TI  - Changes in lipid composition of Blumeria graminis f.sp. tritici conidia produced
      on wheat leaves treated with heptanoyl salicylic acid.
AB  - Treatment of wheat leaves with heptanoyl salicylic acid (HS) and trehalose at
      concentrations of 0.1 and 15 g l(-1), prior to fungal inoculation, resulted in
      40% and 60% protection, respectively, against powdery mildew. The total lipid
      composition of Blumeria graminis f.sp. tritici (Bgt) conidia, the causal agent of
      wheat powdery mildew, was compared when produced on wheat leaves, respectively,
      untreated and treated with the two elicitors, HS and trehalose. An obvious effect
      was observed on lipid composition (sterol and fatty acid (FA)) of Bgt conidia
      produced on wheat leaves treated with HS. A total of 16 FA (C12-C24 saturated and
      unsaturated) as well as unusual methoxylated Fatty Acids (mFA) (3
      methoxydocosanoic and 3-methoxytetracosanoic acids) were detected in the conidia.
      Medium chain FA were predominant in HS treated conidia (64.65%) while long chain
      fatty acids constituted the major compounds in untreated conidia (62%). The long
      chain/medium chain FA ratio decreased from 1.8 in the conidia produced on
      untreated leaves to 0.5 in the conidia obtained from HS treated leaves. When
      comparing the sterol composition of Bgt conidia produced on leaves treated with
      HS versus conidia obtained from untreated ones, very important changes within the
      two major classes can be seen. In particular, 24-methylsterols, e.g., 24
      methylenecholesterol and 24-methylcholesta-7,24-dien were reduced by about 82%
      whereas 24-ethylsterols, e.g., 24-ethylcholesterol and 24-ethylcholesta-5,22
      dienol were increased by about 85%. The 24-methylsterols/24-ethylsterols ratio
      was reduced by ninefold in the conidia produced from HS treated leaves.

PMID- 16647728
TI  - Alkaloids from Toddalia aculeata.
AB  - Two alkaloids N-methyl-4-hydroxy-7-methoxy-3-(2,3-epoxy-3-methylbutyl)-1H
      quinolin-2-one (1) and 3-(2,3-dihydroxy-3-methylbutyl)-4,7-dimethoxy-1-methyl-1H
      quinolin-2-one (2a) have been isolated from CH(2)Cl(2):methanol (1:1) and
      methanol extracts of leaves and stems of Toddalia aculeata. Their structures
      along with that of 15 other compounds, of which three are isolated for the first
      time from genus Toddalia, were established by their detailed spectral studies
      including 2D NMR viz. (1)H-(1)H COSY, (1)H-(13)C COSY, and HMBC.

PMID- 16647729
TI  - Phytosterol biosynthesis pathway in Mortierella alpina.
AB  - The Zygomycetes fungus Mortierella alpina was cultured to growth arrest to assess
      the phytosterol biosynthesis pathway in a less-advanced fungus. The mycelium was
      found to produce 13 sterols, but no ergosterol. The sterol fractions were
      purified to homogeneity by HPLC and their identifies determined by a combination
      of GC-MS and 1H NMR spectroscopy. The principal sterol of the mycelium was
      cholesta-5, 24-dienol (desmosterol) (83%), with lesser amounts of 24beta-methyl
      cholesta-5,25(27)-dienol (codisterol) (2%), 24-methyldesmosterol (6%), 24(28)
      methylene cholesterol (3%) and lanosterol (3%) and several other minor compounds
      (3%). The total sterol accounted for approximately 0.07% of the mycelial dry wt.
      Mycelium fed methionine-methyl-2H3 for 6 days, generated 3 2H-24-methyl(ene)
      sterols, [C28-2H2]24(28)-methylenecholesterol, [C28-2H3]24-methylcholesta-5,24
      dienol and [C28-2H3]24beta-methyl-cholesta-5,25(27)-dienol. The formation of the
      24-methyl sterols seems to be catalyzed by the direct methylation of a common
      Delta24-acceptor sterol thereby bypassing the intermediacy of an isomerization
      step for rearrangement of the Delta24(28)-bond to Delta25(25)-position as
      operates in Ascomycetes fungi and all plants.

PMID- 16647730
TI  - Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular
      modifications.
AB  - Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly
      reactive species with a role in various pathological processes such as cancer,
      chronic inflammation, and cardiovascular and neurological diseases. In the
      present study, the effect of the carotenoids, lycopene and beta-carotene, on
      peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and
      proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly
      inhibited DNA strand breaks caused by peroxynitrite generated from 3
      morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA
      damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1
      dose-dependently increased nitration of proteins in cells above basal levels as
      determined by Western blotting. This nitration was inhibited in the presence of
      the uric acid as well as lycopene. Physiological concentrations (0.31-10 microM)
      of lycopene and beta-carotene also had protective effects on DNA damage, as
      measured by the comet assay. Lycopene significantly reduced DNA damage
      particularly, in the median range of concentrations (2.5 microM). The protective
      effects of lycopene and beta-carotene could be due to their scavenging of
      reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of
      intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5%
      and 42.4%, respectively. The results obtained in this study suggest that
      carotenoids may alleviate some of the deleterious effects of peroxynitrite and
      possibly other reactive nitrogen species as well in vivo.

PMID- 16647731
TI  - Molecular diversity of coronaviruses in bats.
AB  - The existence of coronaviruses in bats is unknown until the recent discovery of
      bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other
      bat species. Among 309 bats of 13 species captured from 20 different locations in
      rural areas of Hong Kong over a 16-month period, coronaviruses were amplified
      from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA
      dependent-RNA-polymerase (pol) and helicase genes revealed six novel
      coronaviruses from six different bat species, in addition to the two previously
      described coronaviruses. Among the six novel coronaviruses, four were group 1
      coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from
      rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV
      HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV
      HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An
      astonishing diversity of coronaviruses was observed in bats.

PMID- 16647732
TI  - The VPgPro protein of Turnip mosaic virus: in vitro inhibition of translation
      from a ribonuclease activity.
AB  - A role for viral encoded genome-linked (VPg) proteins in translation has often
      been suggested because of their covalent attachment to the 5' end of the viral
      RNA, reminiscent of the cap structure normally present on most eukaryotic mRNAs.
      We tested the effect of Turnip mosaic virus (TuMV) VPgPro on translation of
      reporter RNAs in in vitro translation systems. The presence of VPgPro in either
      wheat germ extract or rabbit reticulocyte lysate systems lead to inhibition of
      translation. The inhibition did not appear to be mediated by the interaction of
      VPg with the eIF(iso)4E translation initiation factor since a VPg mutant that
      does not interact with eIF(iso)4E still inhibited translation. Monitoring the
      fate of RNAs revealed that they were degraded as a result of addition of TuMV
      VPgPro or of Norwalk virus (NV) VPg protein. The RNA degradation was not the
      result of translation being arrested and was heat labile and partially EDTA
      sensitive. The capacity of TuMV VPgPro and of (NV) VPg to degrade RNA suggests
      that these proteins have a ribonucleolytic activity which may contribute to the
      host RNA translation shutoff associated with many virus infections.

PMID- 16647733
TI  - Mechanisms underlying the perceived angular velocity of a rigidly rotating
      object.
AB  - The perceived angular velocity of an ellipse undergoing a constant rate of
      rotation will vary as its aspect ratio is changed. Specifically, a "fat" ellipse
      with a low aspect ratio will in general be perceived to rotate more slowly than a
      "thin" ellipse with a higher aspect ratio. Here we investigate this illusory
      underestimation of angular velocity in the domain where ellipses appear to be
      rotating rigidly. We characterize the relationship between aspect ratio and
      perceived angular velocity under luminance and non-luminance-defined conditions.
      The data are consistent with two hypotheses concerning the construction of
      rotational motion percepts. The first hypothesis is that perceived angular
      velocity is determined by low-level component-motion (i.e., motion-energy)
      signals computed along the ellipse's contour. The second hypothesis is that
      relative maxima of positive contour curvature are treated as non-component, form
      based "trackable features" (TFs) that contribute to the visual system's
      construction of the motion percept. Our data suggest that perceived angular
      velocity is driven largely by component signals, but is modulated by the motion
      signals of trackable features, such as corners and regions of high contour
      curvature.

PMID- 16647734
TI  - Retinal adaptation responses revealed by global flash multifocal
      electroretinogram are dependent on the degree of myopic refractive error.
AB  - PURPOSE: There is evidence that the inner retina is involved in eye growth
      control processes and the development of myopia. We sought to investigate the
      response dynamics of the inner retina of adult emmetropes and myopes using the
      global flash multifocal electroretinogram (mfERG) paradigm. METHODS: Fourteen
      myopes and 10 emmetropic subjects (mean age: 21.0+/-2.8 years) underwent mfERG
      testing using VERIS 5.1.5X. The global flash stimulus array consisted of 103
      scaled hexagons which flickered according to a pseudorandom binary m-sequence
      (2(13)-1). The stimulation sequence was modified by inserting three frames, a
      dark frame, a global (full screen) flash, and another dark frame. The amplitude
      and implicit time of the two distinct waveform features, an early direct
      component (DC) and a later induced component (IC) of the first-order kernel were
      analyzed. Retinal responses were averaged over rings of increasing eccentricity,
      or into nasal and temporal hemifields. RESULTS: There was a significant
      correlation between the DC and IC response amplitude and myopic refractive error,
      i.e., the greater the myopic error, the greater the response amplitude. However,
      when comparing between the two refractive error groups, DC and IC response
      amplitudes of emmetropes and myopes were similar, even after compensating for the
      effect of axial length. There were no significant differences in implicit times
      of the DC and IC in emmetropes and myopes. CONCLUSIONS: Global flash mfERG
      responses of emmetropes and myopes were not found to be significantly different.
      The measured retinal adaptation response however varied according to the degree
      of myopia. We hypothesize that dopamine, a neurotransmitter that plays a key role
      in retinal adaptation and is known to be reduced in myopic eyes, may be involved
      in the retinal adaptation effect observed.

PMID- 16647736
TI  - Adaptive norm-based coding of facial identity.
AB  - Identification of a face is facilitated by adapting to its computationally
      opposite identity, suggesting that the average face functions as a norm for
      coding identity [Leopold, D. A., O'Toole, A. J., Vetter, T., & Blanz, V. (2001).
      Prototype-referenced shape encoding revealed by high-level aftereffects. Nature
      Neuroscience, 4, 89-94; Leopold, D. A., Rhodes, G., Muller, K. -M., & Jeffery, L.
      (2005). The dynamics of visual adaptation to faces. Proceedings of the Royal
      Society of London, Series B, 272, 897-904]. Crucially, this interpretation
      requires that the aftereffect is selective for the opposite identity, but this
      has not been convincingly demonstrated. We demonstrate such selectivity,
      observing a larger aftereffect for opposite than non-opposite adapt-test pairs
      that are matched on perceptual contrast (dissimilarity). Component identities
      were also harder to detect in morphs of opposite than non-opposite face pairs. We
      propose an adaptive norm-based coding model of face identity.

PMID- 16647737
TI  - Motion perception deficits in albino ferrets (Mustela putorius furo).
AB  - Albino ferrets contrary to their pigmented conspecifics show no optokinetic
      nystagmus. Therefore, in this study motion perception was compared between
      pigmented and albino ferrets (Mustela putorius furo) trained to discriminate
      between coherently moving random dot patterns and dynamic noise stimuli in a two
      alternative forced choice task. Fully coherently versus incoherently moving
      patterns could be distinguished by ferrets of both phenotypes. Motion coherence
      thresholds, however, were significantly higher in albinos. These results indicate
      that albino ferrets are not motion blind as could be expected from their total
      lack of optokinetic reactions. However, they are severely impaired in global
      motion perception.

PMID- 16647738
TI  - Slow flash multifocal electroretinogram in myopia.
AB  - PURPOSE: The purpose of this study was to investigate the characteristics of
      retinal function in myopes using a modified multifocal electroretinogram (mfERG)
      protocol, the slow flash (sf-mfERG) paradigm, which is thought to primarily
      reflect responses of ON- and OFF-bipolar cells and emphasize the late response
      components. METHODS: Twenty-eight subjects (10 emmetropes and 18 myopes)
      underwent mfERG testing using VERIS 5.1.5X. The sf-mfERG stimulus array consisted
      of 103-scaled hexagons and flickered according to a pseudorandom binary m
      sequence (2(13)-1). The stimulation sequence was slowed by inserting three dark
      frames such that each step in the m-sequence was four frames long (53.3ms). The
      amplitude and implicit time of the major sf-mfERG waveform features (N1, P1, and
      N2) of the first-order kernel were analysed. RESULTS: Myopes had significantly
      reduced P1 and N2 amplitudes compared to the emmetropes (F(1,25)=8.818, p=0.007;
      F(1,25)=6.723, p=0.017). There were no significant differences in N1 amplitude or
      implicit time between the groups (F(1,25)=1.506, p=0.233; F(1,25)=1.291,
      p=0.269). CONCLUSIONS: Late response components (P1 and N2) of the first-order sf
      mfERG responses were preferentially affected in myopia, suggesting possible
      reduced ON- and OFF-bipolar cell activity. As bipolar cells form the first
      synapse of the visual system with the photoreceptors to initiate the ON- and OFF
      pathways, future investigations of ON- and OFF-systems in myopia are of interest.

PMID- 16647739
TI  - Perception of visual motion coherence by rats and mice.
AB  - The coherence thresholds to discriminate the direction of motion in random-dot
      kinematograms were measured in rats and mice. Performance was best in the rats
      when dot displacement from frame-to-frame was about 2 degrees, and frame duration
      was less than 100 ms. Mice had coherence thresholds similar to those of rats when
      tested at the same step size and frame duration. Although the lowest thresholds
      in the rats and mice occasionally reached human levels, average rodent values (
      approximately 25%) were 2-3 times higher than those of humans. These data
      indicate that the rodent and primate visual systems are similar in that both have
      local motion detectors and a system for extracting global motion from a noisy
      signal.

PMID- 16647740
TI  - Comparing the retinal structures and functions in two species of gulls (Larus
      delawarensis and Larus modestus) with significant nocturnal behaviours.
AB  - Ring-billed gulls (Larus delawarensis) and gray gulls (Larus modestus) are two
      species active both by day and night. We have investigated the retinal
      adaptations that allow the diurnal and nocturnal behaviours of these two species.
      Electroretinograms and histological analyses show that both species have a duplex
      retina in which cones outnumber rods, but the number of rods appears sufficient
      to provide vision at night. Their retinas respond over the same scotopic dynamic
      range of 3.4logcdm(-2), which encompasses all of the light levels occurring at
      night in their photic environment. The amplitudes of the scotopic saturated a-
      and b-wave responses as well as the photopic saturated b-wave response and the
      photopic sensitivity parameter S are however higher in ring-billed gulls than in
      gray gulls. Moreover, the process of dark adaptation is about 30min faster in
      gray gulls than in ring-billed gulls. Our results suggest that both species have
      acquired in the course of their evolution functional adaptations that can be
      related to their specific photic environment.

PMID- 16647741
TI  - Attention delays perceived stimulus offset.
AB  - Yeshurun and Levy (2003) [Transient spatial attention degrades temporal
      resolution. Psychological Science, 14, 225 -231.] have suggested that visual
      attention enhances the activation of the parvocellular system and thus delays the
      perceived offset of a stimulus. We tested this assumption in a spatial cueing
      paradigm in which participants responded to stimulus offset. Consistent with this
      assumption, offset reaction time (RT) was prolonged for attended compared to
      unattended stimuli. For onset RT, however, we confirmed the well-known spatial
      cueing effect that attention speeds up the detection of stimulus onset. The
      results provide direct evidence for the proposal made by Yeshurun and Levy.

PMID- 16647742
TI  - High frequency edges (but not contrast) predict where we fixate: A Bayesian
      system identification analysis.
AB  - A Bayesian system identification technique was used to determine which image
      characteristics predict where people fixate when viewing natural images. More
      specifically an estimate was derived for the mapping between image
      characteristics at a given location and the probability that this location was
      fixated. Using a large database of eye fixations to natural images, we determined
      the most probable (a posteriori) model of this mapping. From a set of candidate
      feature maps consisting of edge, contrast and luminance maps (at two different
      spatial scales), fixation probability was dominated by high spatial frequency
      edge information. The best model applied compressive non-linearity to the high
      frequency edge detecting filters (approximately a square root). Both low spatial
      frequency edges and contrast had weaker, but inhibitory, effects. The
      contributions of the other maps were so small as to be behaviourally irrelevant.
      This Bayesian method identifies not only the relevant weighting of the different
      maps, but how this weighting varies as a function of distance from the point of
      fixation. It was found that rather than centre surround inhibition, the
      weightings simply averaged over an area of about 2 degrees.

PMID- 16647743
TI  - GIS supported calculations of (137)Cs deposition in Sweden based on precipitation
      data.
AB  - It is of interest to know the spatial variation and the amount of (137)Cs e.g. in
      case of an accident with a radioactive discharge. In this study, the spatial
      distribution of the quarterly (137)Cs deposition over Sweden due to nuclear
      weapons fallout (NWF) during the period 1962-1966 was determined by relating the
      measured deposition density at a reference site to the amount of precipitation.
      Measured quarterly values of (137)Cs deposition density per unit precipitation at
      three reference sites and quarterly precipitation at 62 weather stations
      distributed over Sweden were used in the calculations. The reference sites were
      assumed to represent areas with different quarterly mean precipitation. The
      extent of these areas was determined from the distribution of the mean measured
      precipitation between 1961 and 1990 and varied according to seasonal variations
      in the mean precipitation pattern. Deposition maps were created by interpolation
      within a geographical information system (GIS). Both integrated (total) and
      cumulative (decay corrected) deposition densities were calculated. The lowest
      levels of NWF (137)Cs deposition density were noted in north-eastern and eastern
      parts of Sweden and the highest levels in the western parts of Sweden.
      Furthermore the deposition density of (137)Cs, resulting from the Chernobyl
      accident was determined for an area in western Sweden based on precipitation
      data. The highest levels of Chernobyl (137)Cs in western Sweden were found in the
      western parts of the area along the coast and the lowest in the east. The sum of
      the deposition densities from NWF and Chernobyl in western Sweden was then
      compared to the total activity measured in soil samples at 27 locations.
      Comparisons between the predicted values of this study show a good agreement with
      measured values and other studies.

PMID- 16647744
TI  - Test emission characteristics of motorcycles in Central Taiwan.
AB  - Due to the large population and high levels of motorized-vehicle exhaust
      emissions, motorcycle emissions make an important contribution to total emissions
      in Taiwan, ROC. Aiming to reduce the air pollution generated by these
      motorcycles, the Taiwan Environmental Protection Administration (TEPA) has
      maintained an enforced inspection and maintenance (I/M) program for in-use
      motorcycles since 1996. This report explores the effects of engine type, engine
      size, engine age, and manufacturers of in-use motorcycles on CO/HC emissions in
      I/M testing data during the period of 1996-2002 in the Central Air Quality Basin
      of Taiwan. Additionally, geographical characteristics and failure rates of
      motorcycles are analyzed. The results indicate that the age, size, and type of
      engine, and the manufacturers of motorcycles all play a significant role in
      determining I/M emission test results. The findings also show that two-stroke
      motorcycles emitted approximately ten times greater HC than those of four-stroke
      motorcycles. CO/HC test emissions increase with a decrease in engine size, HC
      test emissions contributed by Yamaha and other manufacturers being the highest.
      Although CO/HC test emissions generally increase with the age of the motorcycle,
      older motorcycles do not contribute significantly to total emissions due to the
      small number of older motorcycles. It was observed that CO/HC test emissions
      depend on driving patterns, geographical location, and inspection rates of
      motorcycles. The failure rate due to CO is nearly four times greater than that of
      HC, and the older and smaller-engine-size motorcycles obtain greater failure
      rates. These statistical findings can also provide the EPA of Taiwan or other
      Asian countries with useful information for formulating better environmental
      strategies to manage motorcycles effectively.

PMID- 16647745
TI  - Modelling the dispersion of radionuclides following short duration releases to
      rivers: Part 2. Uptake by fish.
AB  - This paper evaluates and generalizes state-of-the-art approaches for dynamic
      modelling of bioaccumulation in fish resulting from short duration liquid
      discharges of radionuclides ((3)H, (14)C, (60)Co, (134)Cs, (137)Cs, (65)Zn,
      (89)Sr, (90)Sr, (125)I, (131)I, (241)Am, isotopes of Pu and U) to rivers. Based
      on a review of model parameter values, predictions are made of maximum and time
      integrated activity concentrations in fish. A simplified version of the model was
      developed and presented as "look-up" graphs. The influence of various
      environmental parameters on model output was evaluated by sensitivity analysis.
      Maximum and time-integrated concentrations in fish may be predicted for rivers
      based on the river volumetric flow rate and water temperature. It is demonstrated
      that the dynamic model gives lower and more realistic predictions of maximum
      concentrations in fish than the simpler "Concentration Factor" approach. However,
      for time-integrated concentration in fish, and estimation of radiation dose to
      humans from consumption of the fish, the Concentration Factor approach gives
      similar predictions to the dynamic model.

PMID- 16647746
TI  - Treatment of a woman with lupus and thromboembolism and cutaneous intolerance to
      heparins using fondaparinux during pregnancy.

PMID- 16647747
TI  - Advanced vulvar carcinoma: is it worth operating? A perioperative management
      protocol for radical and reconstructive surgery.
AB  - OBJECTIVE: The aim of this study was to characterize the means whereby the
      results could be improved and the morbidity and side-effects minimized, of
      radical and extensive surgery performed together with plastic reconstruction, in
      the treatment of locally advanced and relapsed vulvar carcinoma. METHODS: Between
      May 2000 and November 2004, twenty-three patients with locally advanced or
      relapsed vulvar carcinoma underwent major radical or extended vulvectomy,
      requiring reconstructive surgery. A consistent protocol for the perioperative
      management of these patients, including precautionary measures to reduce the rate
      of early complications, was introduced in the second study period (from November
      2003) to verify the benefit on surgical outcome. RESULTS: An analysis of the
      medical reports showed an improvement in the median time of the postoperative
      course and related morbidity as a consequence of a strict application of the
      management protocol, with consequent decrease of early complications.
      CONCLUSIONS: Reconstructive surgery, which broadens the spectrum of available
      operative therapy in primary and locally recurrent vulvar cancer, is
      characterized by a high complication rate. The application of a strict
      perioperative protocol could reduce the number and the clinical impact of such
      complications.

PMID- 16647748
TI  - Clinical outcome with adjuvant treatment of endometrial carcinoma using intensity
      modulated radiation therapy.
AB  - OBJECTIVE: To assess local control and chronic toxicity with IMRT for adjuvant
      treatment of endometrial carcinoma. METHODS: Forty-seven patients with
      endometrial cancer were treated with adjuvant IMRT and HDR brachytherapy (HDRB).
      The external beam dose was between 45 and 50.4 Gy, and all patients received 10
      Gy in 2 fractions of HDRB to the vaginal cuff. Eight of these patients were
      treated with extended field to include the paraaortic region. RESULTS: IMRT
      dosimetry showed excellent coverage of the planning target volume (PTV) with mean
      PTV 95, PTV 110 and PTV 120 of 97.8%, 8.2% and 0.9% respectively. At a median
      follow-up of 20 months, four patients have recurred at extra pelvic sites. No
      patient had pelvic recurrence. The treatment was well tolerated with late
      toxicities as follows: small bowel grade 1: 25%, rectal grade 1: 2% and bladder
      grade 1: 13%. One patient had grade 3 small bowel toxicity. The 3-year actuarial
      rate of grade 2 or greater toxicity, disease-free survival and overall survival
      rate were 3.3%, 84% and 90%, respectively. CONCLUSIONS: The preliminary analysis
      of IMRT for adjuvant treatment of endometrial carcinoma shows excellent local
      control and low toxicity. However, longer follow-up and more patients are needed
      to ascertain whether the benefits of IMRT treatment seen here translate into long
      term reductions in toxicities and local recurrence.

PMID- 16647749
TI  - Atypical presentations of carboplatin hypersensitivity reactions:
      characterization and management in patients with gynecologic malignancies.
AB  - OBJECTIVES: Carboplatin skin testing (ST) can help identify patients with
      platinum hypersensitivity (PH), however, we have encountered patients who do not
      immediately test positive yet exhibit subtle or delayed allergy symptoms prior to
      PH. We describe the "atypical platinum reactions" (APH) of 14 patients and our
      experience with skin testing and desensitization. METHODS: Retrospective chart
      review was performed on carboplatin-treated patients. Patients with +ST, PH or
      APH were offered desensitization, and the number of successful additional
      treatments was recorded. RESULTS: A total of 73 ST were administered to patients
      receiving their >6th carboplatin cycle. 19 +ST and 10 PH with -ST were
      identified. 14 APH were identified including delayed +ST conversions and allergy
      symptoms. The median onset and duration of symptoms after treatment were 6 and
      3.5 days respectively. 12 APH patients had ST on their next cycle, seven of which
      were immediately positive. ST was positive in 36% of those tested, resulting in a
      negative predictive value of 76%. The median number of carboplatin cycles
      received prior to ST conversion, PH or APH was eight. 29% of patients with a +ST,
      PH, or APH had a prior history of systemic allergic reaction to other medications
      or allergens. Desensitization and dose escalation were successful in 14/20
      patients (70%) for an average of 1.9 cycles/patient. CONCLUSIONS: ST will not
      identify all patients with carboplatin-associated reactions. Careful questioning
      regarding symptoms in between chemotherapeutic cycles may identify patients who
      will benefit from desensitization, allowing continuation of treatment and
      prevention of life-threatening adverse events.

PMID- 16647750
TI  - Gonadotropin secretion and pituitary responsiveness to GnRH in mares with
      granulosa-theca cell tumor.
AB  - Granulosa-theca cell tumors (GTCTs) are able to secrete variable amounts of sex
      steroids and immunoreactive inhibin (ir-INH). Although the pituitary appears to
      be affected by the presence of a GTCT, pituitary responsiveness to exogenous GnRH
      has not been examined. The aims of the present study were to: (i) assess the
      plasma hormone concentrations of ir-INH, gonadotropins and sex steroids in eight
      mares with GTCT and (ii) assess the responsiveness of pituitary gonadotroph cells
      to exogenous GnRH stimulus both before and after tumor removal. In seven mares,
      the contralateral ovary was firm, small and inactive. Histopathological
      observations of the tumors confirmed the presumptive diagnosis of a GTCT. Four
      mares, judged to be in vernal transition period (n=2) and in the breeding season
      (n=2), were used as controls. A single intravenous injection of 40 microg of GnRH
      agonist was given to each mare and blood samples were collected every 15 min from
      2 h before to 4 h after injection. In four GTCT mares, this procedure was
      repeated 20 (n=2) and 90 (n=2) days after tumors removal. All plasma samples were
      analyzed for concentrations of ir-INH, LH, FSH, estradiol-17beta (E2),
      testosterone (T) by RIA and progesterone (P) by EIA. Results showed that E2
      levels were significantly higher (P<0.001) in control animals compared to E2
      levels in GTCT mares before and after surgery. P and T concentrations were not
      statistically different between the groups. Baseline levels of ir-INH were
      greater (P<0.05) in GTCT mares before surgery than in control mares, and
      decreased to undetectable levels after neoplasia ablation. Baseline FSH did not
      differ between control and GTCT animals either before or after the ovaries were
      removed. LH baseline values appeared to be higher for affected mares, but the
      difference was not statistically significant. Maximum release (MR) and area under
      the gonadotrophin release curve (AUC) after the GnRH challenge for both the
      gonadotrophins were similar between the groups.

PMID- 16647751
TI  - Integrated morphophysiological assessment of two methods for sperm selection in
      bovine embryo production in vitro.
AB  - Extensive work was done regarding the ability of Swim up and Percoll gradient to
      select functional sperm for in vitro embryo production (IVP) systems. The aim of
      this work was to compare Swim up and Percoll as methods of sperm selection by
      ultrastructural, biochemical and functional studies. Frozen-thawed semen from two
      bulls (Experiments 1 and 2, respectively) were treated using Swim up or Percoll
      discontinuous gradients. Motility, sperm membrane ultrastructure, sperm proteins,
      in vitro embryo production (insemination doses, cleavage, embryo yield and
      quality) and embryo sex ratio were scored and compared. Electron transmission
      microscopy of outer sperm membranes showed higher (P<0.05) percentage of sperm
      with lost acrosomes in Percoll treated samples compared to Swim up. A
      differential protein pattern was also detected. When in vitro embryo production
      was performed, Percoll gradient produced higher (P<0.05) number of fertilizing
      doses (7.6 versus 5.9, Bull 1; 13.5 versus 7.8, Bull 2) and higher sperm motility
      (90% versus 76.6%, Bull 1; 81.7% versus 68.3%, Bull 2) than Swim up. The
      percentage of cleavage (Day 3) was similar in both treatment groups, whereas
      embryo production rate (Day 7) was higher (39.4% versus 30.2%, Bull 1; 38% versus
      32.4%, Bull 2; P<0.05) when Percoll gradient was used. The percentage of hatched
      embryos (Day 11) and sex ratio did not differ. Total cell counting and embryo
      differential staining (inner cell mass and trophoblast cells) of Day 7 embryos
      showed that Percoll treated sperm produced better quality embryos compared to
      Swim up. We concluded that Percoll had a better performance selecting sperm and
      an enhanced capacity for embryo production when compared with the Swim up
      procedure; this could be attributed to a better acrosome exocytosis, associated
      to the absence of certain membrane proteins.

PMID- 16647752
TI  - Strontium-containing hydroxyapatite bioactive bone cement in revision hip
      arthroplasty.
AB  - Clinical outcome of cemented implants to revision total hip replacement (THR) is
      not as satisfactory as primary THR, due to the loss of bone stock and normal
      trabecular pattern. This study evaluated a bioactive bone cement, strontium
      containing hydroxyapatite (Sr-HA) bone cement, in a goat revision hip hemi
      arthroplasty model, and compared outcomes with polymethylmethacrylate (PMMA) bone
      cement. Nine months after operation, significantly higher bonding strength was
      found in the Sr-HA group (3.36+/-1.84 MPa) than in the PMMA bone cement group
      (1.23+/-0.73 MPa). After detached from the femoral component, the surface of PMMA
      bone cement mantle was shown relatively smooth, whereas the surface of the Sr-HA
      bioactive bone cement mantle was uneven, by SEM observation. EDX analysis
      detected little calcium and no phosphorus on the surface of PMMA bone cement
      mantle, while high content of calcium (14.03%) and phosphorus (10.37%) was found
      on the surface of the Sr-HA bone cement mantle. Even higher content of calcium
      (17.37%) and phosphorus (10.84%) were detected in the concave area. Intimate
      contact between Sr-HA bioactive bone cement and bone was demonstrated by
      histological and SEM observation. New bone bonded to the surface of Sr-HA cement
      and grew along its surface. However, fibrous tissue was observed between PMMA
      bone cement and bone. The results showed good bioactivity of Sr-HA bioactive bone
      cement in this revision hip replacement model using goats. This in vivo study
      also suggested that Sr-HA bioactive bone cement was superior to PMMA bone cement
      in terms of bone-bonding strength. Use of bioactive bone cement may be a possible
      solution overcoming problems associated with the use of PMMA bone cement in
      revision hip replacement.

PMID- 16647753
TI  - Bioconcentration and depuration of copper, cadmium, and zinc mixtures by the
      freshwater amphipod Hyalella azteca.
AB  - The uptake and elimination of copper (Cu), cadmium (Cd), and zinc (Zn) by the
      amphipod Hyalella azteca during exposure to the metals singly and in various
      combinations was examined in controlled laboratory experiments. In single metal
      exposures the accumulation of all metals was rapid and increased with exposure
      time. Copper elimination was slower compared to that for zinc and for cadmium no
      elimination was detected after 5 days in clean water. In the two-metal mixtures
      it appears that the presence of one metal influenced the bioconcentration of the
      other, since the bioconcentration factor (BCF) for copper was higher in the
      presence of cadmium than in the presence of zinc and in the case of cadmium, the
      decrease of K(1) values from cadmium single exposure to the binary and tertiary
      mixtures suggests possible inhibition of cadmium uptake by the other metals. In
      the case of the three-metal mixture the situation is less clear, with both
      increased and decreased BCFs recorded, in comparison to single-metal and two
      metal mixtures, suggesting both stimulation and inhibition of metal accumulation.

PMID- 16647754
TI  - Visuo-spatial neglect: a systematic review of current interventions and their
      effectiveness.
AB  - Left visuo-spatial neglect is a well-recognized predictor of poor functional
      outcome following right hemisphere stroke. Over the past 60 years, 18 different
      methods have been described and evaluated aimed at reducing the effects of this
      impairment. Although there are some grounds for optimism particularly in terms of
      short-term impairment-based effects, the range and degree of disability borne by
      many patients remain high and the clinical effectiveness of the different methods
      viewed in terms of long-lasting functional improvement (i.e. improvement of
      disabilities or handicap) is not clear. A systematic review of the available
      clinically relevant literature, using comparative and stringent levels of
      evidence, indicates that visual scanning training (VST), trunk rotation (TR) or
      repeated neck muscle vibrations (NMV) when associated with an extensive training
      program, mental imagery training, video feedback training and prism adaptation
      (PA) can be recommended for the rehabilitation of patients with left neglect.
      More studies however are needed to determine the optimal paradigm of limb
      activation (LA) eliciting a sustained functional improvement. Sensory
      stimulations alone and Fresnel prisms do not appear to be functionally relevant.
      For the other methods, the actual literature is not sufficient to conclude
      whether or not a long-term functional improvement can be achieved.

PMID- 16647755
TI  - Changes in the function of the inhibitory neurotransmitter system in the rat
      brain following subchronic inhalation exposure to 1-bromopropane.
AB  - 1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in
      industries, but the central neurotoxicity of 1-BP remains to be clarified. In the
      present study, we investigated the effects of subchronic inhalation exposure to 1
      BP vapor on the function of the inhibitory neurotransmitter system mediated by
      gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to
      1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and,
      in order to investigate the expression and function of brain GABA type A (GABAA)
      receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and
      cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices
      were prepared, and the population spike (PS) amplitude and the slope of the field
      excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse
      configuration of the extracellular recording technique. Using the Xenopus oocyte
      expression system, we compared GABA concentration-response curves obtained from
      oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats,
      and observed no significant differences in apparent GABA affinity. On the other
      hand, paired-pulse inhibition of PS amplitude was significantly decreased in the
      hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the
      paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the
      DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3
      and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results
      demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the
      function of the hippocampal GABAergic system, which could be due to changes in
      the expression and function of GABAA receptors, especially the delta subunit
      containing GABAA receptors.

PMID- 16647756
TI  - Brain and optic nerve ischemia in malaria with immune disorders.
AB  - We report an unusual case of Plasmodium falciparum malaria in a European
      returning from tropical regions associating an anterior ischemic optic neuropathy
      and an asymptomatic centropontine myelinolysis. The transient antiphospholipid
      antibodies detected in the patient may have played a role in the ischemic process
      at the origin of this unusual clinical association.

PMID- 16647757
TI  - Cognitive and emotional changes in neurobrucellosis.
AB  - OBJECTIVE: To determine cognitive and emotional changes among neurobrucellosis
      patients. METHODS: The patients with neurobrucellosis and controls with
      brucellosis without neurologic involvement were included in the study.
      Neurobrucellosis was diagnosed by the following criteria: (i) symptoms or
      clinical findings compatible with neurobrucellosis, including headache,
      confusion, mental and emotional changes; (ii) isolation of Brucella spp. from CSF
      and/or demonstration of antibodies to Brucella > or = 1/4 in the CSF; (iii) the
      presence of lymphocytosis, increased protein and decreased glucose levels in the
      CSF; and (iv) clinical improvement with appropriate treatment. Two psychiatrists
      interviewed the patients, and performed the Hamilton Depression Rating Scale
      (HDRS) tests and Mini-Mental State Examination (MMSE) tests. RESULTS: Thirty-four
      neurobrucellosis cases and 30 patients with brucellosis without neurological
      involvement were studied. The mean age was 41 years, 12 (41%) patients were
      female, 13 (46%) patients were farmers, and 7 (25%) patients were housewives.
      Among the neurobrucellosis cases, before the antibiotic therapy, the mean MMSE
      test score was 21.6, one week after the therapy 22.7, and two weeks after the
      therapy 24.3 (p=0.024, and p<0.001, respectively). At the day of admission before
      therapy, the mean of HDRS test was 9.9, one week after therapy it was 7.8, and
      two weeks after therapy it was 5 (p=0.014, and p<0.001, respectively).
      CONCLUSION: The cognitive and emotional disturbances among neurobrucellosis
      patients were documented by MMSE and HDRS tests. These disorders improve by
      antibiotic therapy, without any anti-depressive or anti-psychotic therapy.

PMID- 16647758
TI  - Human ether-a-go-go-related (HERG) gene and ATP-sensitive potassium channels as
      targets for adverse drug effects.
AB  - Torsades de pointes (TdP) arrhythmia is a potentially fatal form of ventricular
      arrhythmia that occurs under conditions where cardiac repolarization is delayed
      (as indicated by prolonged QT intervals from electrocardiographic recordings). A
      likely mechanism for QT interval prolongation and TdP arrhythmias is blockade of
      the rapid component of the cardiac delayed rectifier K+ current (IKr), which is
      encoded by human ether-a-go-go-related gene (HERG). Over 100 non-cardiovascular
      drugs have the potential to induce QT interval prolongations in the
      electrocardiogram (ECG) or TdP arrhythmias. The binding site of most HERG channel
      blockers is located inside the central cavity of the channel. An evaluation of
      possible effects on HERG channels during the development of novel drugs is
      recommended by international guidelines. During cardiac ischaemia activation of
      ATP-sensitive K+ (KATP) channels contributes to action potential (AP) shortening
      which is either cardiotoxic by inducing re-entrant ventricular arrhythmias or
      cardioprotective by inducing energy-sparing effects or ischaemic preconditioning
      (IPC). KATP channels are formed by an inward-rectifier K+ channel (Kir6.0) and a
      sulfonylurea receptor (SUR) subunit: Kir6.2 and SUR2A in cardiac myocytes, Kir6.2
      and SUR1 in pancreatic beta-cells. Sulfonylureas and glinides stimulate insulin
      secretion via blockade of the pancreatic beta-cell KATP channel. Clinical studies
      about cardiotoxic effects of sulfonylureas are contradictory. Sulfonylureas and
      glinides differ in their selectivity for pancreatic over cardiovascular KATP
      channels, being either selective (tolbutamide, glibenclamide) or non-selective
      (repaglinide). The possibility exists that non-selective KATP channel inhibitors
      might have cardiovascular side effects. Blockers of the pore-forming Kir6.2
      subunit are insulin secretagogues and might have cardioprotective or cardiotoxic
      effects during cardiac ischaemia.

PMID- 16647759
TI  - Recognition of depressive symptoms by Chinese subjects: the influence of
      acculturation and depressive experience.
AB  - BACKGROUND: We have previously found that the level of acculturation in Chinese
      subjects influences reporting of depression. It is not clear to what extent such
      differences in reporting are a consequence of differences in the recognition of
      depressive symptoms. This study examined the influence of acculturation and
      personal depressive experience on recognition of depressive symptoms in a sample
      of Chinese subjects and controls in a western region. METHOD: A 35-item
      Depressive Symptom Questionnaire was given to 385 Chinese subjects, grouped
      according to their language preference, and 143 non-Chinese Controls all
      recruited from general practices. Subjects rated recognition of symptoms on a 3
      point scale according to the likelihood of someone who had depression
      experiencing each of the 35 symptoms. Three symptom dimensions were extracted
      using factor analysis: core, cognitive and somatic symptoms. The influence of
      acculturation and previous experience of depression on these symptom dimensions
      was examined. RESULTS: The level of acculturation in the Chinese influenced the
      recognition of 'somatic' and 'cognitive' symptoms, but the Chinese groups did not
      differ from Controls in recognition of 'core' symptoms. Previous experience of
      depression led to greater recognition of all three dimensions of symptoms,
      regardless of level of acculturation. CONCLUSIONS: Westernized Chinese, despite
      varying levels of acculturation, appeared capable of recognizing depressive
      symptoms as well as Control subjects. This suggests that the influence of
      acculturation on reporting on depressive symptoms may be due to factors other
      than the recognition of depression. This study has implications for the early
      detection of depression among the Chinese in differing geographical regions.

PMID- 16647760
TI  - The relationship between posttraumatic stress disorder following spinal cord
      injury and locus of control.
AB  - OBJECTIVE: This study examined whether locus of control was associated with
      spinal cord injury posttraumatic stress disorder (SCI-PTSD). METHODS: Sixty-two
      SCI patients and 54 people without SCI participated in the study. The patients
      were assessed using the Posttraumatic Stress Disorder Checklist (PCL), the
      General Health Questionnaire-28 (GHQ-28) and the Multidimensional Health Locus of
      Control (MHLC). The control group was assessed using the GHQ-28 and the MHLC.
      RESULTS: Forty-four percent of patients suffered from full-blown PTSD. SCI
      patients experienced significantly more general health problems than the control.
      Type of SCI and trauma recency were not significantly correlated with PTSD
      symptoms or general health problems but previous traumatic events were.
      Regression analyses showed that internal health locus of control (IHLC) and
      powerful other locus of control (POLC) predicted the re-experiencing symptom;
      IHLC predicted the avoidance symptom; POLC predicted GHQ-28 total. CONCLUSION:
      SCI patients' perceptions of whether their health was or was not determined by
      their own behaviour (i.e. internal or external locus of control) were associated
      with SCI-PTSD.

PMID- 16647761
TI  - Acceptability of routine screening for perinatal depression.
AB  - BACKGROUND: To assess the acceptability of routine screening for perinatal
      depression. METHOD: Postnatal women (n=860) and health professionals (n=916) were
      surveyed after 3 years of routine perinatal (antenatal and postnatal) use of the
      Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Over 90% of women had the
      screening explained to them and found the EPDS easy to complete; 85% had no
      difficulties completing it. Discomfort with screening was significantly related
      to having a higher EPDS score. A majority of health professionals using the EPDS
      was comfortable and found it useful. LIMITATIONS: The sample involved only
      maternity services supporting depression screening. In addition, the response
      rate from GPs was low. CONCLUSIONS: Routine screening with the EPDS is acceptable
      to most women and health professionals. Sensitive explanation, along with staff
      training and support, is essential in implementing depression screening.

PMID- 16647762
TI  - Validating the soft bipolar spectrum in the French National EPIDEP Study: the
      prominence of BP-II 1/2.
AB  - BACKGROUND: Much of the current literature on bipolar disorder is focused on
      bipolar I (BP-I), and to a much lesser extent on bipolar II (BP-II). The French
      multi-center national EPIDEP study has, among its objectives, the feasibility of
      validating a broader spectrum of bipolarity (the so-called "soft spectrum") by
      practicing clinicians. In this report we test aspects of a bipolar schema
      proposed earlier by Akiskal and Pinto [Akiskal, H.S., Pinto, O., 1999. The
      evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am.
      22: 517-534.]. METHODS: EPIDEP was scheduled in three phases: Phase 1 to recruit
      DSM-IV major depressives; Phase 2 to assess hypomania and affective temperaments;
      and Phase 3 to obtain history on course of illness, family history, and
      comorbidity. Comparative analyses are presented between affective subgroups
      constructed on a hierarchical basis: spontaneous hypomania (BP-II), cyclothymic
      temperament (BP-II 1/2), antidepressant-associated hypomania (BP-III),
      hyperthymic temperament (BP-IV), versus "strict unipolar" (UP). RESULTS: We
      present data on 490 patients for whom we obtained full assessment during all
      three phases of the study, classified as BP-II 1/2 (N=164), II (N=61), III
      (N=28), IV (N=22), as well as UP (N=174) as the reference nonbipolar group.
      Systematic inter-group comparison among the soft spectrum showed significant
      differences along clinical, descriptive, course, pharmacologic response and
      familial affective disorder patterns, which confirm the heterogeneity of the soft
      bipolar spectrum, with special characteristics for each of the subgroups. In
      terms of external validation, familial bipolar loading characterized all soft
      bipolar subgroups except type IV. LIMITATION: Data collection conducted in a
      practice setting, clinicians cannot be entirely held "blind" to all measures.
      This is an exploratory attempt, with many variables examined, to help
      characterize the clinical terrain of soft bipolarity. CONCLUSION: This is
      nonetheless the first systematic clinical attempt to validate the bipolar
      spectrum beyond mania (BP-I). BP-II 1/2, BP-III and BP-IV appeared distinct from
      BP-II and strict UP -- along most of the variables examined. BP-II 1/2 -- with
      early onset complex temperament structure, and high mood instability, rapid
      switching, irritable ("dark") hypomania and suicidality -- emerged as the most
      prevalent and severe expression of the bipolar spectrum, and accounting for 33%
      of all MDE. These results, which are of great public health relevance, testify to
      the cyclic nature of bipolarity in its softest expressions. The soft phenotypes
      are also of interest for genetic investigations of bipolar disorder.

PMID- 16647763
TI  - The changing immunological paradigm in coeliac disease.
AB  - When coeliac disease is referred to as an inflammatory disorder, this may detract
      from its true nature. Activation of innate and adaptive immunity takes place in
      the mucosal lesion, but the tissue reaction is not that of classical
      inflammation. In fact, coeliac disease contrasts strikingly with typical
      inflammatory bowel disorders such as ulcerative colitis and Crohn's disease. The
      coeliac lesion apparently reflects, in the main, immune-driven remodelling of
      mucosal architecture with only a minor inflammatory component - initially most
      likely resulting from innate signals. Complement split products might be one of
      several potential initial hits that lead to activation of lamina propria and
      epithelial cells with release of mediators such as interleukin-15. This cytokine
      appears to stimulate potentially pathogenic intraepithelial lymphocytes. In
      genetically susceptible individuals, such early innate events could turn into
      persistent pathogenic signalling with subsequent adaptive cellular and humoral
      immunopathology resulting in a chronic lesion. Nevertheless, mucosal homeostasis
      is surprisingly well preserved as signified by the remarkable dominance of plasma
      cells that produce dimeric immunoglobulin A as a basis for enhanced secretory
      immunity. This shows that the microvascular endothelium in the lesion largely
      maintains its 'gatekeeper' function for mucosal immune cells - in striking
      contrast to the 'promiscuous' situation in inflammatory bowel disease.
      Altogether, a two-signal model is emerging for the pathogenesis of coeliac
      disease - signal 1 generated by innate immunity and signal 2 by adaptive
      immunity. Hence, there is currently an increased focus on immune activation in
      the epithelial compartment rather than on changes in the microvasculature as a
      basis for classical inflammation.

PMID- 16647764
TI  - Evaluation of HIV antibody and antigen/antibody combination ELISAs for use in an
      alternative confirmatory HIV testing strategy in Dar es Salaam, Tanzania.
AB  - The aim of this study was to evaluate the performance of two antibody enzyme
      linked immunosorbent assays (ELISAs) [Vironostika Uni-Form II plus O and
      Enzygnost anti-HIV-1/2 Plus], and two antigen/antibody combination ELISAs [Murex
      and Vironostika HIV Uni-Form II] for use in an alternative confirmatory HIV
      diagnostic testing strategy in Dar es Salaam, Tanzania. Altogether, 1380 serum
      samples were included. All ELISA reactive samples were tested using the Inno-Lia
      antibody assay and discrepant samples were tested on the Innotest p24 antigen
      assay. Three hundred and one (21.8%) samples were confirmed HIV-1 antibody
      positive by Inno-Lia including 27/508 (5.3%) from blood donors, 65/511 (12.7%)
      from pregnant women and 209/361 (57.9%) from hospital patients. The sensitivity
      at initial testing was 100% (95% CI; 98.8-100%) for all assays except Vironostika
      Uni-Form II plus O (99.7%; 95% CI; 98.2-99.9%) which showed one false negative
      sample at initial testing but 100% sensitivity after repeat testing. The final
      specificity at repeat testing was 100% (95% CI; 99.7-100%) for Enzygnost anti-HIV
      1/2 Plus, 99.4% (95% CI; 98.8-99.8%) for each of the antigen/antibody combination
      ELISAs and 97.9% (95% CI; 96.8-98.6%) for Vironostika plus O ELISA. An
      alternative confirmatory HIV testing strategy based on initial testing on any of
      the two antigen/antibody assays followed by testing of reactive samples on the
      Enzygnost anti-HIV-1/2 Plus assay gave 100% specificity (95% CI; 99.7-100%).

PMID- 16647765
TI  - In vitro and in vivo anti-retroviral activity of the substance purified from the
      aqueous extract of Chelidonium majus L.
AB  - We have isolated a substance with anti-retroviral activity from the freshly
      prepared crude extract of Chelidonium majus L. (greater celandine) by 9
      aminoacridine precipitation method and ion exchange chromatography using Dowex
      50W/H+ resin followed by the gel filtration on Sephadex-75 column. Elemental and
      phenol/sulfuric acid method analyses as well as the mass spectrometry of the
      purified substance indicated that it may represent a low-sulfated poly
      glycosaminoglycan moiety with molecular weight of approximately 3800 Da. The
      substance prevented infection of human CD4+ T-cell lines AA2 and H9 with HIV-1 at
      concentration of 25 microg/mL as well as the cell-to-cell virus spread in H9
      cells continuously infected with HIV-1, as determined by the measurement of
      reverse transcriptase activity and p24 content in cell cultures. Furthermore, we
      have shown in a murine AIDS model that the treatment with purified substance
      significantly prevented splenomegaly and the enlargement of cervical lymph nodes
      in C57Bl/6 mice chronically infected with the pool of murine leukemia
      retroviruses. The mechanism(s) of anti-retroviral activity of this substance have
      to be elucidated.

PMID- 16647766
TI  - Analysis of spatial orientation strategies of male and female Wistar rats in a
      Morris water escape task.
AB  - In the present study we investigated spatial navigation in male and female Wistar
      rats in the Morris water escape task. Rats were subjected to procedures which
      required the use of a place (PLACE), cue (CUE) and egocentric (EGO) response to
      learn the task efficiently. In a first experiment rats were successively tested
      in the PLACE, CUE and EGO condition and in a second experiment the order of tasks
      was reversed. The first experiment showed that female rats swam longer distances
      and took more time to find the platform in the PLACE task. Further, the female
      rats spent less time near the previous platform position than the male rats
      during probe trial. No sex difference was found in the CUE and EGO task. In the
      second experiment, the female rats took longer to find the platform than the male
      rats in the EGO task. In the CUE and PLACE task no differences between the sexes
      was found during acquisition. However, the male rats spent more time near the
      previous platform position than the female rats during the probe trial of the
      PLACE task. On basis of present data it is concluded that the use of a PLACE
      based strategy is better in male Wistar rats. CUE learning is not sex-dependent.
      The ability to use EGO strategies appears not to be different between male and
      female Wistar rats, but appears dependent on pre-exposure to the task.

PMID- 16647767
TI  - Does the pre-existing inflammation play a role in the increased C-reactive
      protein levels in acute myocardial infarction?

PMID- 16647768
TI  - Kounis syndrome associated with hypersensitivity to hymenoptera stings.
AB  - Hymenoptera stings can induce acute coronary syndromes by different pathogenetic
      mechanisms including direct action of the venom constituents on the coronary
      endothelium or allergic reaction with mediators acting on the coronary
      vasculature. Two patients were stung by wasps and honeybees and developed Kounis
      syndrome as a consequence of allergic reaction. Kounis syndrome is the
      concurrence of acute coronary syndromes with mast cell activation induced by
      allergic or hypersensitivity and anaphylactic of anaphylactoid reactions. It is
      caused via inflammatory mediators released through mast cell activation. The
      patients had pre-existing coronary artery disease (type II variant of Kounis
      syndrome) and the allergic reaction induced by hymenoptera stings seems to have
      triggered inflammatory mediator release. The pathophysiology and clinical
      implications of this association are discussed.

PMID- 16647769
TI  - Apnea/hypopnea index and benzodiazepine use in patients with arterial
      hypertension and excessive weight.
AB  - Sleep apnea may be associated to psychological symptoms and to increase use of
      antidepressant drugs. It is unknown if the use of benzodiazepines, psychoactive
      drugs with a depressant effect on the brain, is similar, in this regard, to
      antidepressant drugs use. Thirty patients with treated arterial hypertension and
      excessive weight (body mass index >25), either regularly using (13 patients) or
      not using (17 patients) benzodiazepines, were studied, by comparing the
      apnea/hypopnea index measured in a sleep study in both groups. Cardiac left
      chamber dimensions, corrected QT interval, body weight, height and mass index, as
      well as cervical and abdominal circumferences, were additional parameters under
      study. The mean apnea/hypopnea index was found to be significantly greater in
      patients not under chronic benzodiazepine use, when compared to the other group
      of patients (21.8+/-12.4, n=17 versus 9.7+/-11.3, n=13, p<0.05). Mean cervical
      and abdominal diameters were also greater in patients not treated with
      benzodiazepines. We conclude that, in this small group of patients with treated
      arterial hypertension and excessive weight, chronic benzodiazepine therapy was
      not associated with a greater mean apnea/hypopnea index. Further studies are
      needed to establish if, in fact, an inverse association might exist.

PMID- 16647770
TI  - Health insurance and imperfect competition in the health care market.
AB  - We show that when health care providers have market power and engage in Cournot
      competition, a competitive upstream health insurance market results in over
      insurance and over-priced health care. Even though consumers and firms anticipate
      the price interactions between these two markets - the price set in one market
      affects the demand expressed in the other - Pareto improvements are possible. The
      results suggest a beneficial role for Government intervention, either in the
      insurance or the health care market.

PMID- 16647771
TI  - Task demand effects on postural control in older adults.
AB  - The literature shows conflicting results regarding older adults' (OA) postural
      control performance. Differing task demands amongst scientific studies may
      contribute to such ambiguous results. Therefore, the purpose of this study was to
      examine the performance of postural control in older adults and the relationship
      between visual information and body sway as a function of task demands. Old and
      young adults (YA) maintained an upright stance on different bases of support
      (normal, tandem and reduced), both with and without vision, and both with and
      without room movement. In the more demanding tasks, the older adults displayed
      greater body sway than the younger adults and older adults were more influenced
      by the manipulation of the visual information due to the room movement. However,
      in the normal support condition, the influence of the moving room was similar for
      the two groups. These results suggest that task demand is an important aspect to
      consider when examining postural control in older adults.

PMID- 16647772
TI  - Quantitative measurement of handwriting in the assessment of drug-induced
      parkinsonism.
AB  - Monitoring drug-induced side effects is especially important for patients who
      undergo treatment with antipsychotic medications, as these drugs often produce
      extrapyramidal side effects (EPS) resulting in movement abnormalities similar to
      parkinsonism. Scientists have developed several objective laboratory tests to
      measure and research drug-induced movement disorders, but equipment and tests are
      complex and costly and have not become accepted in large-scale, multi-site
      clinical trials. The goals of this study were to test whether a simple
      handwriting measure can discriminate between individuals with psychotropic
      induced parkinsonism, Parkinson's disease, and healthy individuals, and to
      examine some of the psychometric properties of the measure. We examined pen
      movement kinematics during cursive writing of a standard word in 13 patients with
      idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced
      parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants
      were instructed to write the word "hello" in cursive twice, at three vertical
      height scales. Software was used for data acquisition and analysis of vertical
      stroke velocities, velocity scaling, and smoothness. There were four important
      results from this study: (1) both SZ patients with drug-induced EPS and PD
      participants exhibited impaired movement velocities and velocity scaling; (2)
      performance on the velocity scaling measure distinguished drug-induced EPS from
      normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities
      in movement smoothness; and (4) there was a positive correlation between age and
      magnitude of the velocity scaling deficit in PD participants. This study
      demonstrates that kinematic analyses of pen movements during handwriting may be
      useful in detecting and monitoring subtle changes in motor control related to the
      adverse effects of psychotropic medications.

PMID- 16647773
TI  - Glutamate transporters GLAST and EAAT4 regulate postischemic Purkinje cell death:
      an in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4.
AB  - Cerebellar Purkinje cells represent a group of neurons highly vulnerable to
      ischemia. Excitotoxicity is thought to be an important pathophysiological
      mechanism in Purkinje cell death following ischemia. The glutamate transporter is
      the only mechanism for the removal of glutamate from the extracellular fluid in
      the brain. Therefore, glutamate transporters are believed to play a critical role
      in protecting Purkinje cells from ischemia-induced damage. Two distinct glutamate
      transporters, GLAST and EAAT4, are expressed most abundantly in the cerebellar
      cortex. GLAST is expressed in Bergmann glia, whereas EAAT4 is concentrated in the
      perisynaptic regions of Purkinje cell spines. However, the in vivo functional
      significance of these glial and neuronal glutamate transporters in postischemic
      Purkinje cell death is largely unknown. To clarify the role of these glutamate
      transporters in the protection of Purkinje cells after global brain ischemia, we
      evaluated Purkinje cell loss after cardiac arrest in mice lacking GLAST or EAAT4.
      We found that Purkinje cells with low EAAT4 expression were selectively lost
      after cardiac arrest in GLAST mutant mice. This result demonstrates that GLAST
      plays a role in preventing excitotoxic cerebellar damage after ischemia in
      concert with EAAT4.

PMID- 16647774
TI  - A novel double-layered photobioreactor for simultaneous Haematococcus pluvialis
      cell growth and astaxanthin accumulation.
AB  - This study proposes a novel double-region photobioreactor to simplify the
      commercial two-stage process of astaxanthin production by the cultivation of
      Haematococcus pluvialis. The feasibility of the double-region photobioreactor has
      been investigated and found to achieve high biomass yield in the inner core
      region and simultaneous astaxanthin accumulation in the outer jacket region.
      Among many environmental factors, light condition and nitrate level were
      manipulated for selective cell growth and astaxanthin production. In the outer
      jacket region, efficient astaxanthin production was accomplished by excessive
      irradiation (770+/-20 microE m(-2)s(-1)) and nitrate starvation, resulting in a
      dramatic increase of astaxanthin productivity (357 mg l(-1)). Meanwhile,
      attenuated light energy (40+/-3 microE m(-2)s(-1)) and sufficient nitrates were
      supplied to the vegetative cells in the inner core region, which continued to
      grow to a high cell concentration of 4.0 x 10(5) cells ml(-1). The sequential
      batch run was performed by utilizing the high-density vegetative cells as
      inoculum for the next batch run. The cultivation results exhibited similar trends
      as the previous run, reaching high cell density (4.3 x 10(5) cells ml(-1)) in the
      inner core region and high astaxanthin content (5.79% on a dry weight basis) in
      the outer jacket region. The present study indicates that the double-region
      photobioreactor and its method of operation possess a good potential for
      commercial production of astaxanthin by H. pluvialis.

PMID- 16647775
TI  - A serological screening assay of human immunodeficiency virus type 1 antibodies
      based on recombinant protein p24-gp41 as a fusion protein expressed in
      Escherichia coli.
AB  - The objective of this study was expression of a recombinant fusion protein p24
      gp41 to gain a proper folding pattern of the proteins which could be recognized
      by specific antibodies against human immunodeficiency virus type 1 (HIV-1) for
      development of a reliable serodiagnostic kit. Serodiagnostic method using enzyme
      linked immunosorbent assay (ELISA) with the expressed recombinant fusion protein
      p24-gp41 was carried out to test the sensitivity and specificity of the protein
      using human sera and various reference panels from Boston Biomedica Inc. (BBI).
      The level of the expression was determined to be 30% and the final recovery from
      fermentation and purification process was calculated as 80 mg/L with more than
      98% purity. The developed ELISA assay was demonstrated to have 100 and 99.5%
      sensitivity and specificity, respectively, detecting anti-HIV-1 antibody using
      900 positive and 10,000 negative human sera. The developed assay showed reliable
      results in comparison with other reference HIV ELISA kits using various BBI
      panels as well. In conclusion, the recombinant fusion protein p24-gp41 was
      expressed and used to develop a serodiagnostic kit for screening of the HIV-1
      with high sensitivity (100%) and specificity (99.5%) which could be useful for
      screening large groups of blood donors.

PMID- 16647776
TI  - Optimization of wastewater feeding for single-cell protein production in an
      anaerobic wastewater treatment process utilizing purple non-sulfur bacteria in
      mixed culture condition.
AB  - Impacts of operation timing of feeding and withdrawal on anaerobic wastewater
      treatment utilizing purple non-sulfur bacteria have been investigated in mixed
      culture condition with acidogenic bacteria. Simulated wastewater containing
      glucose was treated in a laboratory-scale chemostat reactor, changing the timing
      of wastewater feeding and withdrawal. Rhodopseudomonas palustris, which does not
      utilize glucose as a substrate, was inoculated in the reactor. Rps. palustris was
      detected by a fluorescent in situ hybridization (FISH) technique using the
      specific Rpal686 probe. As a result, population ratios of Rps. palustris were
      over 20% through the operation. Rps. palustris could grow by utilizing
      metabolites of acidogenic bacteria that coexisted in the reactor. A morning feed
      was effective for a good growth of purple non-sulfur bacteria. A protein content
      of cultured bacteria was the highest when wastewater was fed in the morning.
      Dissolved organic carbon (DOC) removal was 94% independent of the timing control.
      Consequently, feeding in the morning is the optimum feed-timing control from the
      aspects of growth of purple non-sulfur bacteria and single-cell protein
      production.

PMID- 16647777
TI  - Coupled transcription-and-translation in Xenopus oocyte and egg extracts.
AB  - Coinjection of T7 promoter-driven plasmids and T7 RNA polymerase (T7 RNAP) into
      Xenopus oocytes results in robust protein synthesis, due to simultaneous gene
      transcription-and-translation (TnT) in the oocyte cytoplasm [Geib, S., Sandoz,
      G., Carlier, E., V. Cornet, Cheynet-Sauvion, V., De Waard, M., 2001. A novel
      Xenopus oocyte expression system based on cytoplasmic coinjection of T7-driven
      plasmids and purified T7-RNA polymerase. Receptors Channels 7, 331-343; Tokmakov,
      A.A., Matsumoto, E., Shirouzu, M., Yokoyama, S., 2006. Coupled cytoplasmic
      transcription-and-translation--a method of choice for heterologous gene
      experession in Xenopus oocytes. J. Biotechnol. 122, 5-15]. In the present study,
      we demonstrate that the TnT reaction of protein synthesis can be reconstituted in
      cell-free extracts of Xenopus oocytes and eggs. Similar to the reaction in
      oocytes, the effective coupling of bacteriophage T7 RNAP-mediated transcription
      with the eukaryotic translation machinery takes place in the Xenopus oocyte and
      egg extracts. However, the kinetics of protein and RNA production in the extracts
      are quite different from those observed in oocytes. Potent RNA synthesis in the
      extracts starts immediately after the addition of T7 promoter-driven DNA and T7
      RNAP and continues for about 30 min, followed by RNA degradation. The protein
      product is detectable in the extracts in 15 min after the initiation of the TnT
      reaction. Efficient protein synthesis in the extracts continues for about 1h. The
      productivity of this expression system can be boosted by the additions of an
      RNase inhibitor and an ATP-regeneration system, and by extract dilution. Kinetic
      analyses suggested that extending the lifetime of the extracts would further
      increase their productivity.

PMID- 16647778
TI  - Purification and characterization of a novel caffeine oxidase from Alcaligenes
      species.
AB  - Alcaligenes species CF8 isolated from surface water of a lake produced a novel
      serine type metallo-caffeine oxidase. The optimal medium for caffeine oxidase
      production by this strain was (w/v) NaNO(3), 0.4%; KH(2)PO(4), 0.15%;
      Na(2)HPO(4), 0.05%; FeCl(3).6H(2)O, 0.0005%; CaCl(2).2H(2)O, 0.001%;
      MgSO(4).7H(2)O, 0.02%; glucose, 0.2%; caffeine, 0.05%, pH 7.5. The enzyme was
      purified to 63-fold by using ammonium sulfate precipitation, dialysis, ion
      exchange (diethylaminoethyl-cellulose) and gel filtration (Sephadex G-100)
      chromatographic techniques. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis revealed that the purified caffeine oxidase was monomeric with a
      molecular mass of 65 kDa. The purified caffeine oxidase with a half-life of 20
      min at 50 degrees C had maximal activity at pH 7.5 and 35 degrees C. The purified
      caffeine oxidase had strict substrate specificity towards caffeine (K(m) 8.94
      microM and V(max) 47.62 U mg protein(-1)) and was not able to oxidize xanthine
      and hypoxanthine. The enzyme activity was not inhibited by para
      chloromercuribenzoic acid, iodoacetamide, n-methylmaleimide, salicylic acid and
      sodium arsenite indicating the enzyme did not belong to xanthine oxidase family.
      The enzyme was not affected by Ca(+2), Mg(+2) and Na(+), but was completely
      inhibited by Co(+2), Cu(+2) and Mn(+2) at 1mM level. The novel caffeine oxidase
      isolated here from Alcaligenes species CF8 may be useful in biotechnological
      processes including waste treatment and biosensor development.

PMID- 16647779
TI  - Application of on-line OUR measurements to detect actions points to improve
      baculovirus-insect cell cultures in bioreactors.
AB  - The continuous monitoring of a process based on the culture of Sf9 insect cells
      and infection by a baculovirus as a vector to obtain recombinant VP2 protein is
      studied. On-line OUR determination is based on the direct oxygen measurement in
      the cell culture vessel and the application of the dynamic method. This
      approximation allows a proper description of cell growth, with precise
      identification of the balanced cell growth end and the most important action
      times in the process, as virus infection time and final cell harvesting. A
      detailed study of the OUR profiles allows on-line monitoring of the effects of
      infection and expression protein process, a tool enabling the automatisation of
      the protein production process in a baculovirus-insect cell system. These
      parameters have been defined as time of action (TOAs), and include the most
      relevant actions to take in these type of processes: time of infection (TOI),
      time of feeding (TOF) and time of harvesting (TOH).

PMID- 16647780
TI  - Hyaluronic acid and its derivative as a multi-functional gene expression
      enhancer: protection from non-specific interactions, adhesion to targeted cells,
      and transcriptional activation.
AB  - Hyaluronic acid (HA), a natural anionic mucopolysaccharide, can be deposited onto
      the cationic surface of DNA/polyethyleneimine (PEI) complexes to recharge the
      surface potential and reduce nonspecific interactions with proteins. HA can also
      be used as a ligand to target specific cell receptors. Furthermore, HA-coating
      enhanced the transcriptional activity of the plasmid/PEI complexes, probably by
      loosening the tight binding between DNA and PEI, which facilitated the approach
      of transcription factors. Amphoteric HA derivative having spermine side chains
      (Spn-HA) with a structure similar to HMG protein showed higher transcription
      enhancing activity than HA. Plasmid/PEI/Spn-HA ternary complex exhibited 29-fold
      higher transgene expression efficiency than naked plasmid/PEI complexes in CHO
      cells.

PMID- 16647781
TI  - Diabetes and Ramadan: review of the literature.
AB  - During the month of Ramadan, Muslims fast every day from dawn to sunset. In the
      healthy subject, this fasting does not have any harmful consequences on health.
      However, it can induce several complications for patients with diabetes. The aim
      of this review twofold: first, it seeks to give some clues about methodological
      aspect of research during Ramadan and to show the impact of various diabetes
      monitoring and treatment, including biochemical and clinical parameters, diet and
      caloric intake, drug intake when fasting. Second, it intends to determine whether
      or not Ramadan fasting induces complications in patients with types 1 and 2
      diabetes and ultimately to elaborate some advice as to the management of fasting
      patients. Several studies have shown that Ramadan fasting did not alter
      biochemical parameters in patients with type 2 diabetes. However, other studies
      have shown that there is either an increase or a decrease in biochemical
      parameters during Ramadan. Ramadan fasting would be acceptable for patients with
      well-balanced type 2 diabetes who are conscious of their disease and compliant
      with their diet and drug intake. If patients with type 1 diabetes wish to fast,
      it is necessary to advise them to undertake control of their glycaemia several
      times a day. Patients with type 1 diabetes who will fast during Ramadan may be
      better managed with fast absorption insulin.

PMID- 16647782
TI  - The Taxus drug-eluting stent: a new paradigm in controlled drug delivery.
AB  - The advent of drug-eluting stents (DES) has provided the medical community with a
      technology that is transforming the treatment of coronary artery disease. As the
      newest treatment modality available to the interventional cardiologist, drug
      eluting stents have not only significantly reduced the risk of restenosis, but
      they are also allowing the interventionalists to treat more complex lesions in
      patients that would otherwise require more invasive bypass surgery. Development
      of these drug-device combination products has presented considerable challenges
      to the device industry because it involves a multi-disciplinary approach that
      combines conventional device design and manufacturing with the principles of
      controlled local drug delivery. This review article provides an in-depth
      discussion of the key elements of drug-eluting stents, focusing on the TAXUS
      paclitaxel-eluting stent as an example of this new class of product. Specific
      sections will review the drug and polymer matrix components, formulation
      development and evaluation, pre-clinical studies and clinical trial results.

PMID- 16647783
TI  - Dual roles of the A kinase-anchoring protein Yotiao in the modulation of a
      cardiac potassium channel: a passive adaptor versus an active regulator.
AB  - Cardiac function is regulated critically by the autonomic nervous system to adapt
      to the physical activity and emotional stress. A slowly activating cardiac
      potassium channel (I(Ks)) is modulated by stimulation of the sympathetic nervous
      system (SNS) and contributes to cardiac action potential shortening in the face
      of concomitant increases in heart rate. Activation of beta-adrenergic receptors
      in response to SNS stimulation results in protein kinase A (PKA)-mediated
      phosphorylation of I(Ks) channels. We have found that the functional regulation
      of the I(Ks) channel by PKA requires the A kinase-anchoring protein (AKAP)
      Yotiao. Yotiao forms a macromolecular complex with the channel and recruits key
      enzymes such as PKA and protein phosphatase 1 (PP1) to control the
      phosphorylation state of I(Ks). Our recent findings revealed a more active role
      of Yotiao in the PKA modulation of I(Ks). We found that Yotiao participates
      actively in translating the phosphorylation-induced change into altered channel
      activity. Moreover Yotiao itself can be phosphorylated by PKA upon beta
      adrenergic stimulation. Ablation of Yotiao phosphorylation impairs PKA-induced
      changes in I(Ks) voltage-dependent activation and current kinetics. Taken
      together we have evidence to suggest that Yotiao plays dual roles in the PKA
      modulation of the I(Ks) channel. It acts not only as an adaptor protein to
      coordinate enzymatic reactions but also as an active regulator that directly
      affects channel function.

PMID- 16647784
TI  - Structure and dynamics of PKA signaling proteins.

PMID- 16647785
TI  - Proceedings of the first International Meeting on Anchored cAMP Signaling
      Pathways, Biomedical Campus, Berlin-Buch, Germany, 15-16 October 2005.

PMID- 16647786
TI  - Human bone marrow stroma cells display certain neural characteristics and
      integrate in the subventricular compartment after injection into the liquor
      system.
AB  - Because the neural differentiation capacity of bone marrow stromal cells (BMSCs)
      is still a matter of controversial debate, we performed a thorough investigation
      into the differentiation capacity of human BMSCs and examined their therapeutic
      potency. BMSCs were isolated from the femur and kept in cell cultures with
      various cultivation protocols being applied. In standard culture conditions using
      a fetal calf serum-enriched medium, while not exhibiting a neural phenotype, the
      majority of cells expressed a variety of neuronal marker proteins as well as the
      astrocyte marker GFAP. Only a minority of stem cells expressed nestin, a marker
      for neural precursor cells. Cultivation in serum-free medium supplemented with
      specific growth factors resulted in a markedly higher percentage of nestin
      positive cells. To establish the therapeutic potency of bone marrow-derived
      cells, the synthesis of neurotrophic factors such as NGF, BDNF and GDNF was
      analyzed under non-stimulating standard culture conditions as well as after a
      neural selection procedure. The therapeutic potency of BMSCs was further examined
      with regard to their migratory potential in vitro and after transplantation in
      vivo. After stereotactic engraftment into the lateral ventricle of adult rats,
      mesenchymal stem cells were seen to adhere to the ependymocytes and cells of the
      choroids plexus. Afterwards grafted cells passed through the ependymal barrier,
      locating in the subventricular space. Their BMSCs took up a close host graft
      interaction without any degenerative influence on the host cells. Furthermore,
      there was morphological as well as immunohistochemical evidence for a
      transdifferentiation within the host tissue. In addition, BMSCs could be
      efficiently transduced using a third-generation adenoviral vector, indicating
      their potential feasibility for a gene-therapeutic option.

PMID- 16647787
TI  - Potential polyphenol markers of phase change in apple (Malus domestica).
AB  - In order to identify potential biochemical markers that can be used as indicators
      for phase change, the dynamics of polyphenolic compounds across apple seedlings
      (Malus domestica, Jonathan x Golden Delicious) were analyzed in this study by
      high performance liquid chromatography. Precocious flowering was induced by
      foliar sprays of plant growth regulators. Qualitative changes in the
      concentration of polyphenols were observed at node nos. 50, 80 and 120.
      Spontaneous and induced flowering was found at node nos. 122 and 77. It was
      reasonable to conclude that node no. 77 represented the point of transition
      between the juvenile phase and the adult vegetative phase, which was marked by
      the presence of phloridzin in the buds. The disappearance of myricitrin in the
      bark and the absence of caffeic acid in the aboveground tissues were qualitative
      markers of the reproductive phase, which was reached at node no. 122.

PMID- 16647788
TI  - Eating for pleasure or just wanting to eat? Reconsidering sensory hedonic
      responses as a driver of obesity.
AB  - Pleasure from foods can stimulate "non-homoeostatic" eating, and might therefore
      also potentially contribute toward obesity. However, obesity is not reliably
      associated with heightened hedonic responses to foods. This apparent discrepancy
      may reflect the differentiation between "liking" and "wanting". Supporting this,
      behavioural and neurophysiological data on responsiveness to food-related cues
      indicate that obesity may be associated with increased motivation for food
      consumption, without necessarily any greater explicit pleasure derived from the
      orosensory experience of eating. This distinction may have important implications
      for further research, and applications in commercial and public health approaches
      to modifying energy intakes.

PMID- 16647789
TI  - Arg-Ile-Tyr (RIY) derived from rapeseed protein decreases food intake and gastric
      emptying after oral administration in mice.
AB  - We previously reported that a bioactive tripeptide Arg-Ile-Tyr (RIY), which has
      been isolated as an inhibitor for angiotensin I-converting enzyme from the
      subtilisin digest of rapeseed protein, decreased blood pressure. In this study,
      we also found that RIY dose-dependently decreased food intake at a dose of 150
      mg/kg after oral administration in fasted ddY male mice. The anorexigenic action
      of RIY was blocked by a cholecystokinin-1 CCK1 receptor antagonist, lorglumide.
      RIY also decreased the gastric emptying rate at a dose of 150 mg/kg and the RIY
      induced delay of gastric emptying was blocked by lorglumide. However, RIY had no
      affinity for CCK1 receptor. Taken together, RIY decreased food intake and gastric
      emptying by stimulating CCK release.

PMID- 16647790
TI  - Pandemic influenza preparedness: the critical role of the syringe.
AB  - In the face of an almost unprecedented threat of a global pandemic of influenza
      it is imperative that stockpiling of appropriate drugs and devices begin now. One
      vital device is an appropriate syringe for delivering vaccine. With the potential
      for millions to be infected and the vaccine supply severely stretched it is
      imperative that the syringe used to vaccinate waste as little vaccine as possible
      and thus allow for a maximum number of persons to be vaccinated. Our study tested
      seven leading candidate vaccine syringes for dosing accuracy, dose-capacity per
      vial, medication wastage and a battery of ergonomic features. One device, the
      Flu+trade mark syringe, proved superior to the others in all important
      categories, possibly due to its low dead-space volume and its dosing accuracy.
      The data suggest that switching to this device from any of the others tested
      would provide between 2 and 19% additional vaccine doses per vial if the current
      10-dose vials are used. Extrapolations from this data suggest that many thousands
      to millions of additional persons could be vaccinated in mass campaigns. Use of a
      syringe of this type, and the vaccine savings that would accrue, would likely be
      important in reducing morbidity and mortality in the event of a pandemic of
      influenza.

PMID- 16647791
TI  - Community cohort study of rotavirus and other enteropathogens: are routine
      vaccinations associated with sex-differential incidence rates?
AB  - OBJECTIVE: Community studies in West Africa have demonstrated that routine
      vaccinations may have non-targeted effects, the female-male mortality ratio being
      reduced after administration of BCG and increased after diphtheria-tetanus
      pertussis (DTP). We examined whether immunisation status was associated with
      infection with rotavirus and other enteropathogens. METHODS: We recruited 200
      children shortly after birth and followed them until 2 years of age with weekly
      morbidity interviews and stool sampling. Vaccination status for each child was
      classified according to the most recent vaccination as documented by vaccination
      card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of
      infection with an enteropathogen and of enteropathogen-associated diarrhoea were
      estimated for children according to whether they had received BCG or DTP as their
      last vaccination. RESULTS: For children who received BCG as their last vaccine,
      the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were
      1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who
      received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89
      4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and
      diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus
      infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively.
      The female-male IRR for rotavirus-associated diarrhoea differed significantly
      among BCG and DTP recipients (p=0.02). Infections with enteropathogens not
      associated with diarrhoea were associated with lower female-male IRRs after BCG
      of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32
      (1.03-1.70) for primary infection (p=0.05). Though there were few infections with
      other diarrhoea-causing enteropathogens, these were also associated with a lower
      female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after
      DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine
      immunisations may affect morbidity for non-targeted infections. As in studies of
      infant mortality, BCG is associated with lower risk for girls, whereas, DTP is
      associated with higher risk for girls relative to boys.

PMID- 16647792
TI  - Rural habitat and risk of death in small areas of Southern Spain.
AB  - The purpose of this paper is to study the linkage between type of habitat and
      mortality from all causes in small areas of Southern Spain. An ecological study
      was conducted on 99,870 people who died between 1985 and 1999. The municipality
      was taken as the unit of analysis. Data analysis was carried out through
      hierarchical spatio-temporal bayesian models. Results show a 13.3% reduction in
      mortality rates among men and 14.1% among women in the most rural areas compared
      to more urban environments. The study demonstrates the usefulness of socio
      demographic indices in small-area geographical analyses.

PMID- 16647793
TI  - Challenges to HIV prevention in psychiatric settings: perceptions of South
      African mental health care providers.
AB  - Mental health services in South Africa increasingly feel the brunt of the AIDS
      epidemic. Despite the high prevalence of infection in the psychiatric setting,
      HIV risk reduction interventions targeting South Africans with psychiatric
      illness remain few and far between. The attitudes of mental health care providers
      about sexual relations and HIV among people with mental illness continue to
      influence the extent to which these issues are addressed in care settings. This
      study examines these attitudes through the use of a semi-structured interview
      administered to 46 mental health care providers in four provinces of South
      Africa. I found that personal, contextual and political factors in the clinic and
      the hospital create barriers to integrating prevention activities. In particular,
      providers face at least three challenges to intervening in the epidemic among
      their patients: their own views of psychiatric illness, the transitions occurring
      in the mental health care system, and shifting social attitudes toward sexuality.
      Barriers operate at the individual level, the institutional level, and the
      societal level. At the individual level providers' perceptions of psychiatric
      symptoms shape their outlook on intervention with psychiatric patients. At the
      institutional level disruptive transitions in service delivery relegate HIV
      services to lesser importance. At the societal level, personal beliefs about
      sexuality and mental illness have remained slow to change despite major political
      changes. Minimizing barriers to implementing HIV prevention services requires
      institutional and health care policies that ensure adequate resources for
      treating people with mental illness and for staff development and support.

PMID- 16647794
TI  - Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women.
AB  - Neuroplastic processes are thought to be involved in the pathophysiology of many
      psychiatric disorders, including major depression. It has been hypothesized that
      the brain-derived neurotrophic factor (BNDF), a key factor in neuroplasticity, is
      associated with depressive disorders. Our study evaluated the pre- and post
      treatment levels of BDNF in a group of depressed patients and compared them with
      healthy controls. In order to exclude the effects of gender on neuroplasticity,
      our study group was restricted to women exclusively and consisted of 20
      depressive patients and 20 healthy controls, with similar age and educational
      level distribution. Blood samples were collected before the treatment and on the
      sixth week of the treatment with 10 mg S-citalopram. The pre-treatment BDNF
      levels of the depressed patients were found to be lower than those of the healthy
      subjects. During the sixth week, the BDNF levels of depressive patients were
      significantly higher than the pre-treatment levels but similar to those of
      control subjects. These findings suggest that BDNF level may be an important
      factor in the etiopathogenesis of depression and may have a role in the action
      mechanism of antidepressant drugs.

PMID- 16647795
TI  - Posttraumatic stress disorder and body mass index in military veterans.
      Preliminary findings.
AB  - INTRODUCTION: Current management of posttraumatic stress disorder (PTSD) focuses
      on the psychiatric parameters of this condition. Little has been written about co
      morbid overweight and obesity in PTSD. METHODS: We used the database of the
      recently constituted PTSD program at the Hunter Holmes McGuire Veterans Affairs
      Medical Center in Richmond, Virginia to assess and better understand the
      prevalence and severity of overweight and obesity among military veterans with
      PTSD. Variables assessed included age, decade of life, height, weight, sex, race,
      and severity and chronicity of PTSD. We used PTSD CheckList-Military Version (PCL
      M) to assess current complaints and service-connected disability (SCD) to
      estimate the long-term severity of PTSD. RESULTS: Of the 221 male veterans
      extracted from our PTSD database for purposes of this study, 144 (65.2%) were in
      the age range of 50 to 59 years consistent with Vietnam veterans dominating our
      study population. Their mean body mass index (BMI) was 30.2+/-5.8 kg/m(2) placing
      the typical veteran in the obese range. Far exceeding the current US population
      rate of 64.5%, 82.8% of our study population was either overweight or obese. Our
      sample had BMI measurements greater than those reported for non-PTSD veterans and
      also BMI measurements reported in the literature for veterans with PTSD. Current
      (PCL-M) and long-term (SCD) markers of PTSD did not relate to obesity.
      CONCLUSIONS: The prevalence of overweight and obesity among our veterans with
      PTSD far exceeded current US population findings and those of other veteran
      groups with and without PTSD. PTSD symptoms, whether assessed acutely or
      chronically, did not explain our findings. Prospective studies of PTSD and
      comorbidity are needed using larger study populations to better understand the
      relationships among PTSD, stress, and obesity.

PMID- 16647796
TI  - Benefits of combining aripiprazole to clozapine: three case reports.
AB  - OBJECTIVE: A substantial number of patients treated with clozapine shows
      insufficient response. The author presents the results of adding aripiprazole in
      patients resistant to clozapine. METHOD: Three cases of individuals with
      psychotic symptoms despite clozapine use and with significant side effects that
      were treated via this combination are presented. Response was evaluated by
      clinical assessment. RESULTS: Good clinical results were obtained in all three
      patients, with improvement of psychotic symptoms and of some of the side effects
      of clozapine. CONCLUSION: The findings from this case series suggest that
      adjunctive therapy with aripiprazole can be of benefit for treating clozapine
      resistant schizophrenic patients.

PMID- 16647797
TI  - Effect of benzo[a]pyrene on P-glycoprotein-mediated transport in Caco-2 cell
      monolayer.
AB  - The main exposure pathway of benzo[a]pyrene (Bap) for humans is considered to be
      via the daily diet. The purpose of this study was to investigate the effect of
      BaP on the intestinal transport of chemicals mediated by P-glycoprotein (P-gp).
      The intestinal epithelial membrane transport of rhodamine-123 (Rho-123), a
      substrate of P-gp, was examined using a monolayer of the human Caco-2 cell line
      grown in transwells. In the monolayer exposed to Bap for 72 h before transport
      experiments, the ratio of the apparent permeability coefficients (P(app)) of Rho
      123 efflux increased compared to that of the control. The permeability of
      rhodamine-B (Rho-B), not a substrate of P-gp, showed no difference between the
      monolayers. Treatment with quinidine or cyclosporine A, which are P-gp
      inhibitors, decreased the P(app) of Rho-123 to the same degree in both
      monolayers. The transport of Rho-123 was not influenced by the presence of Bap.
      Thus, Bap seemed not to act directly on the efflux activity of P-gp and be a
      binding site competitor of Rho-123. In the Caco-2 cells that enhanced the efflux
      of Rho-123 by the treatment with Bap, an increase in mRNA expression of MDR 1 (P
      gp) was confirmed compared to that of control by RT-PCR. Furthermore, Western
      blot analysis using a monoclonal antibody, C219, demonstrated the increase of P
      gp in Caco-2 cells exposed to Bap, compared with controls. It was inferred that
      Bap exposure induced the expression of P-gp, which led to the observed increase
      in efflux transport of Rho-123. The possibility was suggested that Bap might
      affect the disposition of medicines by increasing P-gp expression.

PMID- 16647798
TI  - Hydrophobic collapse in late-stage folding (in silico) of bovine pancreatic
      trypsin inhibitor.
AB  - Hydrophobic collapse is commonly considered as a process of significance for
      protein folding. Many models have been applied for description of this event. A
      model introducing an external force field mimicking the hydrophobic environment
      and simultaneously the driving force for the folding process is presented in this
      paper. Bovine pancreatic trypsin inhibitor (BPTI) was taken as a test protein. An
      early-stage folding (in silico) model presented elsewhere was used to create the
      starting structure for hydrophobic collapse. The resulting structure was energy
      refined using molecular dynamics simulation in an explicit solvent. The
      similarity versus the crystal structure of BPTI is estimated using visual
      analysis, residue-residue contacts, phi, psi angle distributions, RMSD,
      accessible solvent area, radii of gyration and hydrodynamic radii. A program
      allowing creation of early-stage folding structural forms to be created for any
      protein is available from http://bioinformatics.cm-uj.krakow.pl/earlystage. The
      program for late-stage folding simulation is available on request.

PMID- 16647799
TI  - Eccles' perspective of the forebrain, its role in skilled movements, and the mind
      brain problem.
AB  - Sir John Eccles' experimental life evolved from the "bottom" up: the synapse to
      the modular circuitry of the spinal cord, later the cerebellum and, less
      extensively, also the thalamus and hippocampus. He experimented quantitatively on
      basic properties of cell membranes, synapses, transmitters, cellular modules,
      reflexes, and plasticity. In parallel, he was also motivated to consider
      philosophical problems of mind-brain interactions. It was mostly during Eccles'
      "Swiss period" (1976-1997) that new experimental work advanced understanding of
      intentional motor actions and their preparation. For example, early brain imaging
      work suggested that the so-called "supplementary" motor area was rather a
      "supramotor" area, concerned with intentional preparation to move. Eccles also
      closely followed work on cortico-cerebellar integration and learning. His final
      contribution, in collaboration with the quantum physicist, Friedrich Beck, was a
      model of how specific neuronal modules interact with the mind. Being a declared
      dualist, Eccles encountered considerable resistance and skepticism among
      neuroscientists in accepting his experimentally untestable mind-brain theories.
      But one can only admire the remarkable continuity of effort in his search for
      modular operations of identified neurons in the central nervous system and their
      synaptic actions. This effort was facilitated by collaboration with the eminent
      anatomist, Janos Szentagothai, who had previously helped Eccles advance
      understanding of spinal and cerebellar circuitry. This review also includes some
      personal views on current understanding of the forebrain, with an emphasis on the
      multiplicity of cortical modules, all of which contribute in the mental
      preparation for forthcoming intentional actions.

PMID- 16647800
TI  - John Eccles' pioneering role in understanding central synaptic transmission.
AB  - This chapter deals with the central role that Sir John Eccles played in the
      elucidation of the mechanisms of synaptic transmission within the central nervous
      system during the three decades between the late 1930s and 1966. His seminal
      discoveries involved studies of synaptic input to spinal motoneurons using
      intracellular recording via glass micropipettes after their introduction in the
      late 1940s. After defending the hypothesis that electrical currents alone
      explained central synaptic events, his observations of reversal potentials and
      sensitivity to ion injections instantly converted Eccles to the idea that central
      synapses generate postsynaptic potentials, designated IPSPs and EPSPs, by
      liberating chemical transmitters. He and his collaborators used pharmacological
      manipulations of recurrent inhibition to support the idea that a given neuron
      liberates the same chemical transmitter substance at all of its synapses, which
      he called "Dale's Principle". His team worked out the mechanisms and spinal
      circuits underlying disynaptic and recurrent inhibition, as well as those of
      presynaptic inhibition. Not content with the view that central synapses were
      static entities, Eccles also made seminal observations on synaptic plasticity
      induced by alterations in use and disuse. Although his firmly held belief that
      the extensive dendritic trees of motoneurons were essentially irrelevant to
      synaptic events at the soma was later refuted by others in the mid-1960s, Eccles
      stands as a towering figure in the history of neuroscience. His prodigious energy
      and commanding intellect gave the field of central synaptic transmission the
      conceptual bases that have guided it for over 40 years.

PMID- 16647801
TI  - Following autolysis in proteases by NMR: insights into multiple unfolding
      pathways and mutational plasticities.
AB  - Biophysical studies in proteases are severely hampered due to the auto-cleavage
      property of these enzymes. In this context, we develop here a kinetic model and
      an NMR-based strategy to use this very autolytic property to derive useful
      insights into multiple unfolding pathways and mutational plasticities in these
      proteins. The basic idea lies in the interpretation of the auto-cleavage-driven
      decay of the folded protein peaks in the HSQC spectra as a function of time. The
      different peaks are seen to decay at different rates. As unfolding is the rate
      determining step in the auto-cleavage reaction, the NMR spectral changes reflect
      on local unfolding processes at the residue level. A formalism is presented to
      gain insights into unfolding free energies and evaluate local perturbations due
      to single point mutations. The model is applied to HIV-1 protease-tethered dimer
      as an example, considering mutations at a particular site. Significant
      perturbations are seen even at very remote areas from the site of the mutation.

PMID- 16647802
TI  - Reflections on a new artificial urinary sphincter.

PMID- 16647803
TI  - Female sexual dysfunction after pelvic surgery: is there a place for nerve
      sparing surgery?

PMID- 16647804
TI  - Urogenital infections: The pivotal role of the urologist.

PMID- 16647805
TI  - Intrafascial nerve-sparing laproscopic radical prostatectomy: do we really
      preserve relevant nerve-fibres?

PMID- 16647806
TI  - Frozen sections for positive margins?

PMID- 16647807
TI  - Influence of sympathectomy in humans on the rhythmicity of 6-sulphatoxymelatonin
      urinary excretion.
AB  - The amount of 6-sulphatoxymelatonin, the chief metabolite of melatonin, in the
      urine was measured in nine patients, who were subjected to bilateral
      sympathectomy at the second thoracic ganglionic level for treatment of
      hyperhidrosis of the palms. All patients showed before surgery a normal 6
      sulphatoxymelatonin excretion with a peak in the excretion during the night time.
      After the sympathectomy, the high night time excretion was clearly abolished in
      five patients but remained high in four patients. This indicates that the
      segmental locations of the preganglionic sympathetic perikarya in the spinal
      cord, stimulating the melatonin secretion in the pineal gland in humans, vary
      between individuals. An increase in daytime melatonin excretion was observed in
      the patients responding to the sympathectomy with an abolished 6
      sulphatoxymelatonin rhythm. This increase could indicate that the final
      sympathetic neurons innervating the pineal gland might have a both stimulatory
      and inhibitory function.

PMID- 16647808
TI  - Mechanism of pineal-specific gene expression: the role of E-box and photoreceptor
      conserved elements.
AB  - Photoreceptor cells of the pineal gland express distinct sets of proteins
      dedicated to photoreception, phototransduction and to rhythmic melatonin
      production. This review discusses the function of key regulatory sequences and
      nuclear factors that determine tissue-restricted expression of photoreceptor
      genes, specifically, the photoreceptor conserved element (PCE) and the E-box and
      their cognate binding proteins. Recent research in zebrafish revealed that PCE
      and E-box mediate the action of OTX5 and BMAL/CLOCK, respectively. These
      transcription factors drive enhanced expression of serotonin-N-acetyltransferase
      2 (aanat2) in the pineal gland by synergistic interaction. Extensive research of
      other photoreceptor-specific genes suggested that the presence of several PCEs
      along with additional sequence elements is required to drive enhanced tissue
      specific expression of these genes. Therefore, the mechanism identified for
      zebrafish aanat2, or at least part of it, may apply to other photoreceptor
      specific genes in zebrafish and other species.

PMID- 16647809
TI  - The 5 lipoxygenase system in the vasculature: emerging role in health and
      disease.
AB  - Activation of the 5 lipoygenase (5LO) system within the vascular bed requires the
      presence of several cell types with distinct transcellular cross-talk mechanisms,
      resulting in the generation of 5LO produced metabolites and increased expression
      of receptors for these metabolites in vascular cells. The key products in this
      system, the leukotriens LTB4, LTC4 and LTD4, are potent mediators of vascular
      inflammation initiated by white blood cells and sustained or propagated
      thereafter through amplified metabolite generation and direct effects in
      endothelial and vascular smooth muscle cells. Leukotrienes act to enhance cell
      permeability and increase oxidative stress, vascular smooth muscle cell migration
      and arterial tone. 5LO activation is highly regulated, and is apparently both
      model/species-specific and region-specific. 5LO activation is also linked to
      plaque progression, plaque stability, activation of matrix metalloproteinases,
      propensity to coronary and cerebrovascular events and the evolution of aortic
      aneurysms. Genetic variants in the 5LO activating protein are strongly linked to
      increased cardiovascular risk and may serve as useful markers for future therapy
      targeting down regulation of 5LO expression and activity as a means to combat
      cardiovascular disease.

PMID- 16647810
TI  - Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast
      cancer.
AB  - Many members of BCL2 (Bcl-2) apoptosis-related genes were found to be
      differentially expressed in various malignancies and were proposed as prognostic
      cancer biomarkers. Recently, a new member of the BCL2 gene family, BCL2L12, was
      cloned and was found to be expressed in mammary gland. In the present study, 55
      specimens from patients with, histologically confirmed, epithelial breast
      carcinoma were analyzed for BCL2 and BCL2L12 gene expression by RT-PCR. Increased
      expression of BCL2 gene was found in patients belonging to the age groups <45 or
      >55 years, as well as in estrogen receptors (ER)-positive patients and in BCL2L12
      positive tumors. In addition, BCL2 or BCL2L12-positive patients were found to be
      almost four times less likely to relapse or die in comparison to BCL2 or BCL2L12
      negative patients, respectively. Multivariate analysis revealed that BCL2 and
      BCL2L12 might be used as independent prognostic biomarkers in breast cancer.

PMID- 16647811
TI  - Production of aggregate from non-metallic automotive shredder residues.
AB  - In this paper, the results of an experimentation on the production of granules
      suitable to be used as aggregates in cementitious or asphalt mixes are presented
      and discussed. The granules were obtained by granulating the non-metallic
      fraction of automotive shredder residues. In a preliminary separation step the
      fluff fraction containing mainly inert and non-metallic materials was sieved and
      analyzed for the metal content. In the following granulation step, the sieved
      fraction was mixed with binding materials, fly ash and a densifier agent, to
      produce granules of 5-30 mm of diameter and up to 1400 kg/m3 of specific weight.
      The granulation was carried out at room temperature in a rotating tank. Concrete
      samples prepared using as aggregates the produced granules showed a specific
      weight up to 1800 kg/m3 and a compressive strength up to about 55% of reference
      samples prepared using a calcareous aggregate, depending on the fluff content of
      the mixes, and on the nature of the binder and of the other components used.

PMID- 16647812
TI  - Determination of trace metals by atomic absorption spectrometry after
      coprecipitation with europium hydroxide.
AB  - A procedure for the determination of trace amounts of chromium(III), iron(III),
      lead(II) and manganese(II) is described, that combines atomic absorption
      spectrometry-europium hydroxide coprecipitation. The influences of analytical
      parameters including amount of europium(III), amount of ammonia, sample volume,
      etc. were investigated on the recoveries of analyte ions. The effects of
      concomitant ions were also examined. The recoveries of the analyte ions were in
      the range of 95-104%. The detection limits (3 s) were in the range of 1.7-17.1
      microg/L. The validation of the presented coprecipitation procedure was performed
      by the analysis of Bovine Liver 1577-b and BCR-144R Sewage Sludge (domestic
      origin) standard reference materials. The method was applied to the determination
      of analytes in real samples including natural waters and some food, soil and
      fertilizer samples, etc. and good results were obtained (relative standard
      deviations < 10%, recoveries > 95%).

PMID- 16647813
TI  - Synthesis of MCM-41 from coal fly ash by a green approach: influence of synthesis
      pH.
AB  - The present study reports a green synthesis method for preparing pure (free of
      fly ash) and ordered MCM-41 materials from coal fly ash at room temperature (25
      degrees C) during 24 h of reaction. It was shown that the impurities in the coal
      fly ash were not detrimental to the formation of MCM-41 at the tested conditions.
      The influence of initial synthesis pH on material properties of calcined MCM-41
      samples was investigated by various techniques such as XRF, XPS, XRD, FTIR, DR-UV
      vis, solid state NMR, N2 physisorption, TG-DTA, SEM and TEM. The experimental
      results showed that the amount of trace elements such as Al, Na, Ti and Fe
      incorporated into the sample increased with synthesis pH value. More aluminum
      species were incorporated with tetrahedral coordination in the framework under a
      high pH value. The particle size of the sample decreased with the synthesis pH
      value. Samples synthesized at high pH values had a larger pore size and were more
      hydrothermally stable than those at low pH values. From thermal analysis, it was
      observed that the synthesized MCM-41 samples showed a high thermal stability.
      These properties made the synthesized MCM-41 suitable for further processing into
      more useful materials in a wide range of applications.

PMID- 16647814
TI  - Statistical analysis of major accidents in petrochemical industry notified to the
      major accident reporting system (MARS).
AB  - The European major accident reporting system (MARS) was created within the
      framework of European Union (EU) directive 82/501, the so-called "SEVESO"
      directive, and in order to register all the major industrial accidents notified
      to the European Union authorities from the member states. Statistical analysis of
      these accidents offers significant data to the understanding and prevention of
      industrial accidents. This paper makes an analysis of some characteristics of
      major accidents in the petrochemical sector included in MARS. The statistical
      analysis focused on the main categorization fields of the MARS short reports and
      additionally a refinement of the immediate causes of major accidents with focus
      on the organizational factors was attempted through the details provided in the
      full reports of the database.

PMID- 16647815
TI  - Destruction of an industrial wastewater by supercritical water oxidation in a
      transpiring wall reactor.
AB  - The supercritical water oxidation (SCWO) is a technology that takes advantage of
      the special properties of water in the surroundings of critical point of water to
      completely oxidize wastes in residence times lower than 1 min. The problems
      caused by the harsh operational conditions of the SCWO process are being solved
      by new reactor designs, such as the transpiring wall reactor (TWR). In this work,
      the operational parameters of a TWR have been studied for the treatment of an
      industrial wastewater. As a result, the process has been optimized for a feed
      flow of 16 kg/h with feed inlet temperatures higher than 300 degrees C and
      transpiring flow relation (R) between 0.2 and 0.6 working with an 8% (w/w)
      isopropanol (IPA) as a fuel. The experimental data and a mathematical model have
      been applied for the destruction of an industrial waste containing acetic acid
      and crotonaldehyde as main compounds. As the model predicted, removal
      efficiencies higher than 99.9% were obtained, resulting in effluents with 2 ppm
      total organic carbon (TOC) at feed flow of 16 kg/h, 320 degrees C of feed
      temperature and R = 0.32. An effluent TOC of 35 ppm under conditions feed flow of
      18 kg/h, feed inlet temperatures of 290 degrees C, reaction temperatures of 570
      degrees C and R = 0.6.

PMID- 16647816
TI  - 3-Benzidino-6(4-chlorophenyl) pyridazine blocks delayed rectifier and transient
      outward potassium current in acutely isolated rat hippocampal pyramidal neurons.
AB  - 3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine (minaprine) is an
      acetylcholinesterase (AChE) inhibitor. 3-Benzidino-6(4-chlorophenyl) pyridazine
      (BCP) and minaprine have a central pyridazine ring in common. In this study, we
      investigated the effects of BCP on delayed rectifier potassium current (IK(DR))
      and transient outward potassium current (IK(A)) in acutely isolated rat
      hippocampal pyramidal neurons by using whole-cell patch-clamp technique. IK(DR)
      and IK(A) were inhibited by BCP (0.01-500 microM) in a concentration-dependent
      and voltage-dependent manner. The IC50 value for the blocking action of BCP on
      IK(DR) and IK(A) was calculated as 7.13+/-0.18 microM and 0.55+/-0.11 microM,
      respectively. At the concentration of 10 microM, BCP shifted the activation curve
      of IK(DR) to positive potential by 29.09 mV. Meanwhile, at the concentration of
      10 microM, BCP also shifted the activation and inactivation curve of IK(A) to
      positive potential by 34.18 and 22.47 mV, respectively. In conclusion, BCP
      potently inhibits IK(DR) and IK(A) in rat hippocampal pyramidal neurons.

PMID- 16647817
TI  - Seroepidemiology of canine babesiosis and ehrlichiosis in a hospital population.
AB  - Canine ehrlichiosis and babesiosis have a worldwide distribution with geographic
      variation in prevalence and main clinical manifestations. We prospectively
      determined seroprevalence of canine babesiosis and ehrlichiosis, and risk factors
      for seropositivity. Three hundred and eighty-one dogs were randomly selected to
      represent the canine population at a Veterinary Teaching Hospital in south Brazil
      (latitude 23 degrees S). Dogs were tested with a point-of-care ELISA for
      Ehrlichia canis antibodies and IFA to confirm previous exposure to Babesia
      vogeli. Multiple logistic regression analysis was then used to estimate adjusted
      odds ratio (OR) and their 95% confidence intervals. One hundred and thirty-six
      (36%) dogs were seropositive for B. vogeli antibodies, whereas 87 (23%) dogs were
      seropositive to E. canis antibodies. Fifty-four (14%) dogs seroreacted to both
      agents. Adult dogs previously infested with ticks were more likely to seroreact
      to B. vogeli or E. canis. Superficial bleeding (OR = 12.4) was more common in
      dogs exposed to B. vogeli, whereas neurological signs (OR = 7.7) were more common
      in dogs seropositive to E. canis. Neurological signs (OR = 12.0) and lameness (OR
      = 12.8) were more prevalent in dogs that seroreacted to both organisms. Owners of
      dogs with ticks were more likely to have been exposed to ticks themselves (OR =
      3.2). Canine babesiosis and ehrlichiosis appear to be highly prevalent in this
      hospital population. Clinical signs differed from the most common signs in other
      regions with bleeding occurring more in dogs seropositive to babesiosis, but not
      ehrlichiosis; neurologic signs in dogs with E. canis antibodies; and lameness in
      dogs that seroreacted to both organisms.

PMID- 16647818
TI  - Prevalence and genotypes of Giardia duodenalis in 1-2 year old dairy cattle.
AB  - To determine the prevalence of Giardia genotypes in 12-24 month old dairy
      heifers, fecal specimens were collected from two farms each in Vermont, New York,
      Pennsylvania, Maryland, Virginia, North Carolina, and Florida. Specimens, cleaned
      of fecal debris and concentrated using CsCl density gradient centrifugation, were
      subjected to PCR and DNA sequence analysis. Prevalence of Giardia infection,
      ranged from 11% to 75% on 14 farms with an average prevalence of 36% (204
      positive cattle out of 571 examined). DNA sequence analysis of the 16S rRNA gene
      revealed 91% of the 204 Giardia isolates were Assemblage E, and 9% were
      Assemblage A. The prevalence of these genotypes varied greatly from farm to farm,
      with four farms having exclusively Assemblage E Giardia. Overall, Assemblage E
      was present in 33% of all animals tested and Assemblage A was present in 3% of
      the animals. Thus, while many of the heifers were infected with a genotype that
      is not known to be infectious for humans, 1-2 year old heifers on 10 of 14 farms
      did harbor zoonotic Assemblage A Giardia. Therefore, heifers cannot be overlooked
      as a potential source of human infectious cysts in the environment, with some
      farms representing a much higher risk than others.

PMID- 16647819
TI  - Prevalence of Toxocara cati and other parasites in cats' faeces collected from
      the open spaces of public institutions: Buenos Aires, Argentina.
AB  - Toxocarosis is a worldwide parasitic infection that affects both cats and dogs.
      Toxocara cati (Schrank, 1788) syn. Toxocara mystax (Zeder, 1800) prevalence was
      studied in faeces from stray cats collected from the open spaces of public
      institutions of Buenos Aires city, both building and surrounding open spaces are
      fenced off. Of the 465 samples obtained from March to June of 2005, 58.3% were
      found to have parasite eggs. The following parasites were identified from the 271
      positive samples: T. cati (61.2%), Cystoisospora spp. (20.3%), Trichuris spp.
      (17.0%), Toxascaris leonina (15.1%), Ancylostoma spp. (14%) and Aelurostrongylus
      abstrusus (2.6%). T. cati prevalence was 35.7% (95% confidence interval: 31.2
      40.1), with a 42.2% single isolations. The most frequent combination was T. cati
      and Cystoisospora spp. (9%). More than half the areas studied showed over 40%
      prevalence. Seventy-one percent of the collected samples were fresh with a
      variable moist consistency and 29% were older with a dry consistency. A
      statistically significant association was found between sample consistency and
      presence of parasites (chi2 = 10.81; p = 0.001) as also between sample
      consistency and presence of T. cati (chi2 = 11.27; p = 0.0007). Moist
      consistencies were significantly different from the rest: consistency (wet or
      dry) versus parasites (z = 1.95; p = 0.02) (95% confidence interval: 0.004
      0.203); consistency (wet or dry) versus T. cati (z = 3.25; p = 0.0006) (95%
      confidence interval: 0.075-0.254). The cat population that inhabits these public
      green spaces contaminates the environment, thus transforming them into dangerous
      spaces with a variable rate for the human population that spends time in these
      places.

PMID- 16647820
TI  - Prevalence of Cryptosporidium parvum infection in Punjab (India) and its
      association with diarrhea in neonatal dairy calves.
AB  - A prevalence study was contemplated to determine the prevalence of
      Cryptosporidium spp. in dairy farms in Punjab, India. The cryptosporidium oocysts
      were detected from 50 and 25.68% from 80 diarrheic and 74 non-diarrheic animals,
      respectively. Both shedding and intensity of shedding were significant in calves
      with diarrhea. The Cryptosporidium spp. appears to be common in dairy calves and
      an important contributor of calf diarrhea in the Punjab province. The prevalence
      of the infection peaked in young calves between 0 and 30 days in both the
      diarrheic and non-diarrheic groups (86.4 and 66.6%, respectively). The percentage
      distribution of positive samples, with reference to age groups of diarrheic and
      non-diarrheic animals was negatively correlated with increase in age. High
      mortality rate and case fatality rate of 35.2 and 44.4% were observed in young
      calves between 0 and 30 days of age.

PMID- 16647821
TI  - Effect of imidocarb and levamisole on the experimental infection of BALB/c mice
      by Leishmania (Leishmania) amazonensis.
AB  - The adverse effects from using currently available drugs for the treatment of
      leishmaniasis have motivated the search for new therapeutical agents. The aim of
      this work was to evaluate the effect of imidocarb and levamisole on the treatment
      of BALB/c mice experimentally infected by Leishmania (Leishmania) amazonensis.
      BALB/c mice were infected with 10(6) promastigotes of L. (L.) amazonensis
      (IFLA/BR/67/PH8) and, starting on day 51, mice were treated subcutaneously with
      imidocarb (IMD, 34 mg/kg), imidocarb plus levamisole (IMD+LVS, 34 and 12 mg/kg,
      respectively), only levamisole (LVS, 12 mg/kg) or without treatment (control).
      Lesion size and swelling were weekly monitored for 10 weeks after the beginning
      of the treatment. On day 121 post-infection, serum levels of specific IgG from
      infected mice were evaluated, as well as histopathological and morphometric
      alterations in the footpad, lymph nodes and spleen of these animals. The data
      obtained in this study demonstrated that, when compared to controls, mice treated
      with IMD had lower levels of IgG anti-L. (L.) amazonensis (34.45%), smaller
      vacuolar area in macrophages (3.75%), lower number of megakaryocytes in spleen
      (63.19%) and lower parasite burden in the footpad (30.2%). Thus, the evaluated
      parameters suggest the use of imidocarb as a potential drug in the treatment of
      tegumentary leishmaniasis.

PMID- 16647822
TI  - Marijuana use motives: concurrent relations to frequency of past 30-day use and
      anxiety sensitivity among young adult marijuana smokers.
AB  - The present investigation examined two theoretically relevant aspects of
      marijuana motives using the Marijuana Motives Measure (MMM) [Simons, J., Correia,
      C. J., Carey, K. B., & Borsari, B. E. (1998). Validating a five-factor marijuana
      motives measure: Relations with use, problems, and alcohol motives. Journal of
      Counseling Psychology 45, 265-273] among 141 (78 female) young adults
      (M(age)=20.17, S.D.=3.34). The first objective was to evaluate the incremental
      validity of marijuana motives in relation to frequency of past 30-day use after
      controlling for the theoretically relevant factors of the number of years using
      marijuana (lifetime), current levels of alcohol, as well as tobacco smoking use.
      As expected, coping, enhancement, social, and expansion motives each were
      uniquely and significantly associated with past 30-day marijuana use over and
      above the covariates; conformity motives were not a significant predictor. A
      second aim was to explore whether coping, but no other marijuana motive, was
      related to the emotional vulnerability individual difference factor of anxiety
      sensitivity (fear of anxiety). As hypothesized, after controlling for number of
      years using marijuana (lifetime), past 30-day marijuana use, current levels of
      alcohol consumption, and cigarettes smoked per day, anxiety sensitivity was
      incrementally and uniquely related to coping motives for marijuana use, but not
      other motives. These results are discussed in relation to the clinical
      implications of better understanding the role of motivation for marijuana use
      among emotionally vulnerable young adults.

PMID- 16647823
TI  - Cohort comparisons: social learning explanations for alcohol use among
      adolescents and older adults.
AB  - Some researchers have suggested that theories of delinquency are appropriate to
      the study of deviant behavior among older adults. This study compares the
      relative effects of social learning variables on alcohol use and abuse by
      adolescents and older adults. Two sub-samples-aged 12-17 (N=17709) and aged 65
      and older (N=2019)-were created from the 2002 National Household Survey of Drug
      Use and Health, a national probability sample of persons aged 12 and older in the
      United States. Data show that the frequency of alcohol use for adolescents is
      positively associated with personal approval of daily alcohol use and the number
      of peers who get drunk at least once a week, while older adult frequency is
      positively associated with personal approval of daily alcohol use and number of
      peers who use alcohol. Alcohol abuse by adolescents is correlated with personal
      approval of daily alcohol use, the number of peers who drink alcohol, and the
      number of peers who get drunk at least once a week. Among the older adult sub
      sample only personal approval of daily alcohol use and number of peers who use
      alcohol is significantly associated with abuse. These findings provide evidence
      for the merits of applying social learning variables to understanding deviance
      among diverse age cohorts.

PMID- 16647824
TI  - Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic
      actions.
AB  - BACKGROUND: Melatonin exerts oncostatic effects on different kinds of tumors,
      especially on endocrine-responsive breast cancer. The most common conclusion is
      that melatonin reduces the incidence and growth of chemically induced mammary
      tumors, in vivo, and inhibits the proliferation and metastatic behavior of human
      breast cancer cells, in vitro. Both studies support the hypothesis that melatonin
      oncostatic actions on hormone-dependent mammary tumors are mainly based on its
      anti-estrogenic actions. METHODS AND RESULTS: Two different mechanisms have been
      proposed to explain how melatonin reduces the development of breast cancer
      throughout its interactions with the estrogen-signaling pathways: (a) the
      indirect neuroendocrine mechanism which includes the melatonin down-regulation of
      the hypothalamic-pituitary reproductive axis and the consequent reduction of
      circulating levels of gonadal estrogens and (b) direct melatonin actions at tumor
      cell level. Melatonin's direct effect on mammary tumor cells is that it
      interferes with the activation of the estrogen receptor, thus behaving as a
      selective estrogen receptor modulator. Melatonin also regulates the activity of
      the aromatases, the enzymes responsible for the local synthesis of estrogens,
      thus behaving as a selective estrogen enzyme modulator. CONCLUSIONS: The same
      molecule has both properties to selectively neutralize the effects of estrogens
      on the breast and the local biosynthesis of estrogens from androgens, one of the
      main objectives of recent antitumor pharmacological therapeutic strategies. It is
      these action mechanisms that collectively make melatonin an interesting
      anticancer drug in the prevention and treatment of estrogen-dependent tumors,
      since it has the advantage of acting at different levels of the estrogen
      signaling pathways.

PMID- 16647825
TI  - Cloning and characterization of zebrafish CTCF: Developmental expression
      patterns, regulation of the promoter region, and evolutionary aspects of gene
      organization.
AB  - CTCF is a nuclear phosphoprotein capable of using different subsets of its 11 Zn
      fingers (ZF) for sequence-specific binding to many dissimilar DNA CTCF-target
      sites. Such sites were identified in the genomic DNA of various multicellular
      organisms, in which the CTCF gene was cloned, including insects, birds, rodents,
      and primates. CTCF/DNA-complexes formed in vivo with different 50-bp-long
      sequences mediate diverse functions such as positive and negative regulation of
      promoters, and organization of all known enhancer-blocking elements ("chromatin
      insulators") including constitutive and epigenetically regulated elements.
      Abnormal functions of certain CTCF sites are implicated in cancer and in
      epigenetic syndromes such as BWS and skewed X-inactivation. We describe here the
      cloning and characterization of the CTCF cDNA and promoter region from zebrafish,
      a valuable vertebrate model organism. The full-length zebrafish CTCF cDNA clone
      is 4244 bp in length with an open reading frame (ORF) of 2391 bp that encodes 797
      amino acids. The zebrafish CTCF amino acid sequence shows high identity (up to
      98% in the zinc finger region) with human CTCF, and perfect conservation of exon
      intron organization. Southern blot analyses indicated that the zebrafish genome
      contains a single copy of the CTCF gene. In situ hybridization revealed the
      presence of zebrafish CTCF transcripts in all early stages of embryogenesis.
      Transfection assays with luciferase reporter-constructs identified a core
      promoter region within 146 bp immediately upstream of the transcriptional start
      site of zebrafish CTCF that is located at a highly conserved YY1/Initiator
      element.

PMID- 16647826
TI  - A bilogarithmic method for the spectrophotometric evaluation of stability
      constants of 1:1 weak complexes from mole ratio data.
AB  - The absorbance changes that occur when the mole ratio of the components of ligand
      complex equilibria is varied while the concentration of one component is kept
      constant (mole ratio method) allow evaluating stability constants in favourable
      conditions. Values of the corresponding stability (association) constants are
      normally assigned on the basis of spectrophotometric analysis. Determination of
      stability constants can be performed by a number of linear procedures, but most
      of these, suffer from theoretical and practical drawbacks, e.g., linear
      transformation of the rectangular hyperbola type of binding constants, is valid
      only when one of the two species is present in a large excess. A rigorous
      treatment of the experimental mole ratio data for 1:1 weak complexes is carried
      out in this paper with the aim of eliminating some of the assumptions involved in
      the other methods usually applied for evaluating stability constants. Orthogonal
      regression is required in order to take into account the error in both axes. The
      method has been applied to literature data for the iron(III)-thiocyanate and
      nickel(II)-selenocyanate systems, as well as to a number of host-guest
      cyclodextrin complexes.

PMID- 16647827
TI  - Thermodynamic and kinetic characterization of polymorphic transformation of
      famotidine during grinding.
AB  - Two polymorphs of famotidine were prepared by recrystallization from acetonitrile
      for form A and methanol for form B, respectively. The effect of grinding process
      on the polymorphic transformation of famotidine was investigated. Each famotidine
      sample ground for various grinding times in a ceramic mortar was determined by
      differential scanning calorimetry (DSC), conventional and thermal Fourier
      transform infrared (FT-IR) microspectroscopy. The results indicate that the raw
      material of famotidine was proved to be a form B. A unique IR absorption band at
      3505 cm(-1) for famotidine form B gradually decreased its intensity with the
      grinding time, while two newer IR absorption bands at 3451 and 1671 cm(-1) for
      famotidine form A slowly appeared. The peak intensity ratio of 3451/350 5 cm(-1)
      was linearly (r=0.9901) increased with the grinding time, suggesting that the
      grinding process could induce the polymorphic transformation of famotidine from
      form B to form A by a zero-order process. The DSC endothermic peaks also
      confirmed this polymorphic transformation from famotidine form B (167 degrees C,
      DeltaH: 165J/g) to famotidine form A (174 degrees C, DeltaH: 148J/g) in which the
      values of enthalpy were linearly reduced with the increase of grinding time
      (r=0.9943). The phase transition temperature of the different ground famotidine
      samples could be easily and only evidenced by using thermal FT-IR
      microspectroscopy, rather than by DSC analysis. These phase transition
      temperatures of the famotidine form B ground for 5-20 min quickly reduced from
      144 to 134 degrees C and maintained a constant at 134 degrees C even after 20-30
      min grinding. The grinding process not only decreased the crystallinity of
      famotidine form B but also reduced the particle size of famotidine form B,
      resulting in easy induction of the polymorphic transformation of famotidine from
      form B to form A in ground famotidine sample.

PMID- 16647828
TI  - Rate thresholds determine the precision of temporal integration in principal
      cells of the ventral cochlear nucleus.
AB  - The three types of principal cells of the ventral cochlear nucleus (VCN), bushy,
      octopus, and T stellate, differ in the detection of coincidence among synaptic
      inputs. To explore the role of the action-potential-generation mechanism in the
      detection of coincident inputs, we examined responses to depolarizing currents
      that increased at varying rates. To fire an action potential, bushy cells, likely
      of the globular subtype, had to be depolarized faster than 4.8+/-2.8 mV/ms,
      octopus cells faster than 9.5+/-3.6 mV/ms, and T stellate cells fired
      irrespective of the rate of depolarization. The threshold rate of depolarization
      permitted definition of a time window over which depolarization could contribute
      to generating action potentials. This integration window differed between cell
      types. It was 5.3+/-1.8 ms for bushy cells and 1.4+/-0.3 ms for octopus cells. T
      Stellate cells fired action potentials in response to even slow depolarizations,
      showing that their integration window was unlimited so that temporal summation in
      these cells is limited by the time course of synaptic potentials. The rate of
      depolarization threshold in octopus and bushy cells was decreased by alpha
      dendrotoxin while T stellate cells were largely insensitive to alpha-dendrotoxin
      indicating that low-voltage-activated K+ conductances (gKL) are important
      determinants of the integration window.

PMID- 16647829
TI  - Identification of unknown bodies by using CT images of frontal sinus.
AB  - The aim of the study was to define a simple system for the identification of
      unknown bodies by using CT images of frontal sinus and to discuss whether it was
      worth to add measurements to the system or not. The system was including simple
      features as F (presence or absence of frontal sinus), S (intersinus and
      intrasinus septum) and S (scalloping), and named as FSS system. Measurements
      selected for the study were width, height, anteroposterior length, total width of
      two sinuses, the distance between the highest points of the two sinuses and the
      distance of each sinus to its maximum lateral limit. The study was conducted
      retrospectively on the paranasal CT scans of 100 cases (38 male and 62 female)
      who had no apparent sinonasal pathology. All the features and measurements were
      coded according to the system defined by the authors for each case and coded
      formulas were compared. At least 93% of the formulas could be eliminated for a
      case by using FSS system. The rate of success was increased to 98% by adding
      measurements. Contrary to objective criteria of FSS system, measurements were
      prone to bias. Therefore, in practice success rate would be expected to be lower
      than calculated. In the study population, instead of making 100 measurements,
      eliminating the most of the cases with FSS system and later discriminating the
      rest by pattern matching was seen logical.

PMID- 16647830
TI  - Changes in BAER amplitudes after perinatal asphyxia during the neonatal period in
      term infants.
AB  - We recorded serially brainstem auditory evoked response (BAER) during the
      neonatal period in term infants who suffered perinatal asphyxia. The amplitudes
      of BAER components was analysed at 40 dB above BAER threshold of each subject who
      had a threshold<or=25 dB nHL. No apparent changes in the amplitudes of waves I
      and III during the first 5 days after birth. The two wave amplitudes were
      slightly reduced thereafter. On day 30, the amplitudes were slightly smaller than
      in normal controls. No statistical significant differences were found in the two
      amplitudes between the infants after asphyxia and the controls on any days
      studied. In contrast, wave V amplitude showed a trend of reduction during the
      whole neonatal period. The amplitude was reduced slightly on the first day after
      birth, but reduced further on day 3 (ANOVA, P<0.01). Thereafter, the reduction
      persisted without any significant change. On day 30, wave V amplitude remained
      significantly smaller than in the controls (P<0.001). Compared to the controls,
      V/I amplitude ratio was slightly smaller during the neonatal period, but V/III
      amplitude ratio was significantly smaller on most of the days studied (P<0.05
      0.01). The persistent reduction of wave V amplitude suggests a sustained neuronal
      damage of the auditory brainstem in infants after perinatal asphyxia.

PMID- 16647831
TI  - Cardiovascular ageing: a crosstalk between basic science and clinical practise is
      needed!

PMID- 16647832
TI  - Endometrial nitric oxide production and nitric oxide synthases in the equine
      endometrium: Relationship with microvascular density during the estrous cycle.
AB  - Nitric oxide (NO) plays an important role in angiogenesis and in the regulation
      of the blood flow. This study was carried out to investigate (i) the effects of
      endogenous estrogens and progestins and exogenous progesterone (P(4)) (5 ng/ml or
      1 microg/ml) or estradiol 17beta (E(2)beta) (50 pg/ml or 1 microg/ml) on in vitro
      endometrial NO synthesis; (ii) the presence of different isoforms of NO synthase;
      (iii) and their relationship to microvascular density in the equine endometrium
      during the estrous cycle. NOS expression was also evaluated in the myometrium.
      Expression of endothelial and inducible forms of NOS in the uterus was assessed
      by Western blot and immunocytochemistry. Vascular density in endometrial tissue
      was determined on histologic sections. In the luteal phase, compared to the
      follicular phase, endometrial NO production increased without exogenous hormones
      and with exogenous E(2)beta (1 microg/ml). Although immunocytochemistry revealed
      iNOS and eNOS expression in the endometrium, no positive signal for iNOS was
      detected by Western blot. Endothelial NOS was observed in endometrial glands,
      endothelial cells, fibroblasts, blood and lymphatic vessels. Endometrial eNOS
      expression was the highest in the follicular and mid-luteal phases while it was
      found to be the lowest in the early luteal phase. In the follicular phase,
      hyperplasia of endometrial tissue with respect to myometrium was detected. No
      difference in vascular density was present between phases. All together, NO may
      play some roles in both proliferative and secretory phases of endometrial
      development in the mare.

PMID- 16647833
TI  - Fearing the unknown: a short version of the Intolerance of Uncertainty Scale.
AB  - Intolerance of uncertainty is the tendency of an individual to consider the
      possibility of a negative event occurring unacceptable, irrespective of the
      probability of occurrence. It is a key component of worry, state anxiety, and
      related anxiety pathologies. The 27-item Intolerance of Uncertainty Scale (IUS)
      was developed to measure intolerance of uncertainty. Previous psychometric
      analyses of the IUS have suggested both four- and five-factor models. High inter
      item correlations, factor instability, and previous theoretical research support
      the development of a reduced measure. The present study used two undergraduate
      samples and evaluated a psychometrically stable 12-item two-factor version of the
      IUS. The reduced measure (IUS-12) retained exemplary internal consistency, while
      correlating extremely well with the original IUS and related measures of anxiety
      and worry. The IUS-12 also demonstrated a stable two-factor structure,
      representing both anxious and avoidance components of intolerance of uncertainty.
      Directions for future research and potential applications for assessment are
      discussed.

PMID- 16647834
TI  - Detection and management of malingering in people presenting for treatment of
      posttraumatic stress disorder: methods, obstacles, and recommendations.
AB  - Malingering of symptoms of posttraumatic stress disorder (PTSD) has become a
      growing concern, particularly in healthcare and other settings in which the
      diagnosis is associated with financial incentives such as disability benefits.
      Although there is a steadily increasing body of research on methods for detecting
      PTSD malingering, little has been written on the assessment and practical
      management of malingering in treatment settings. The present article addresses
      this important issue, including a review of the methods, obstacles, and possible
      solutions for assessing PTSD malingering, along with suggestions for managing
      cases in which malingering is strongly suspected.

PMID- 16647835
TI  - A possible dose-dependent teratogenic effect of ergotamine.

PMID- 16647836
TI  - Oligonucleotide microarray analysis of strain- and gender-associated gene
      expression in the human blood fluke, Schistosoma japonicum.
AB  - Schistosomiasis is a chronic and debilitating disease caused by blood flukes
      (digenetic trematodes) of the genus Schistosoma. Schistosomiasis japonica, a
      zoonosis caused by Schistosoma japonicum, is endemic to the Philippines and
      China. We utilised a 22,575 feature custom oligonucleotide DNA microarray
      designed from public domain databases of schistosome-expressed sequence tags to
      explore differential gene expression between the Philippine (SJP) and Chinese
      (SJC) strains of S. japonicum, and between male and female S. japonicum. We found
      that 593, 664 and 426 probes were differentially expressed between the two
      geographical strains when we compared mix sexed adults, male worms and female
      worms. Additionally, the study revealed that 1163 male- and 1016 female
      associated probes were differentially expressed in SJP whereas 1047 male- and 897
      female-associated probes were differentially expressed in SJC. The study greatly
      expands previously published data of strain and gender-associated differential
      expression in S. japonicum. Further, these new data provide a stepping stone for
      understanding the complexities of the biology, sexual differentiation,
      maturation, and development of human schistosomes, signaling new approaches for
      identifying novel intervention and diagnostic targets against schistosomiasis.

PMID- 16647837
TI  - Inferential functioning in visually impaired children.
AB  - The current study explores the inferential abilities of visually impaired
      children in a task presented in two formats, manipulative and verbal. The results
      showed that in the group of visually impaired children, just as with children
      with normal sight, there was a wide range of inference types. It was found that
      the visually impaired children perform slightly better in the use of inductive
      and relational inferences in the verbal format, while in the manipulative format
      children with normal sight perform better. These results suggest that in
      inferential functioning of young children, and especially visually impaired
      children, the format of the task influences performance more than the child's
      visual ability.

PMID- 16647838
TI  - Impact of prenatal methylmercury exposure on neurobehavioral function at age 14
      years.
AB  - A cohort of 1022 consecutive singleton births was generated during 1987-1988 in
      the Faroe Islands, where increased methylmercury exposure occurs from traditional
      seafood diets that include pilot whale meat. The prenatal exposure level was
      determined from mercury analyses of cord blood, cord tissue, and maternal hair.
      At age 14 years, 878 of 1010 living cohort members underwent detailed
      neurobehavioral examination. Eighteen participants with neurological disorders
      were excluded. Blood and hair samples obtained from the participants were
      analyzed for mercury. The neuropsychological test battery was designed based on
      the same criteria as applied at the examination at age 7 years. Multiple
      regression analysis was carried out and included adjustment for confounders.
      Indicators of prenatal methylmercury exposure were significantly associated with
      deficits in finger tapping speed, reaction time on a continued performance task,
      and cued naming. Postnatal methylmercury exposure had no discernible effect.
      These findings are similar to those obtained at age 7 years, and the relative
      contribution of mercury exposure to the predictive power of the multiple
      regression models was also similar. An analysis of the test score difference
      between results at 7 and 14 years suggested that mercury-associated deficits had
      not changed between the two examinations. In structural equation model analyses,
      the neuropsychological tests were separated into five groups; methylmercury
      exposure was significantly associated with deficits in motor, attention, and
      verbal tests. These findings are supported by independent assessment of
      neurophysiological outcomes. The effects on brain function associated with
      prenatal methylmercury exposure therefore appear to be multi-focal and permanent.

PMID- 16647839
TI  - Dok5 is substrate of TrkB and TrkC receptors and involved in neurotrophin induced
      MAPK activation.
AB  - Tropomyosin-related kinase (Trk) family receptors are a group of high affinity
      receptors for neurotrophin growth factors, which have pivotal functions in many
      physiological processes of nervous system. Trk receptors can dimerize and
      autophosphorylate upon neurotrophin stimulation, then recruit multiple adaptor
      proteins to transduct signal. In this report, we identified Dok5, a member of Dok
      family, as a new substrate of TrkB/C receptors. In yeast two-hybrid assay, Dok5
      can interact with intracellular domain of TrkB and TrkC receptor through its PTB
      domain, but not with that of TrkA receptor. The interaction was then confirmed by
      GST pull-down assay and Co-IP experiment. Dok5 co-localized with TrkB and TrkC in
      differentiated PC12 cells, providing another evidence for their interaction. By
      using mutational analysis, we characterized that Dok5 PTB domain bound to Trk
      receptor NPQY motif in a kinase-activity-dependent manner. Furthermore,
      competition experiment indicated that Dok5 competed with N-shc for binding to the
      receptors at the same site. Finally, we showed that Dok5 was involved in the
      activation of MAPK pathway induced by neurotrophin stimulation. Taken together,
      these results suggest that Dok5 acts as substrate of TrkB/C receptors and is
      involved in neurotrophin induced MAPK signal pathway activation.

PMID- 16647840
TI  - Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2
      and iNOS gene expression and production of cytokines in LPS-induced macrophages
      and monocytes.
AB  - Macrolides have been reported to modify the host immune and inflammatory
      responses both in vivo and in vitro. We examined the in vitro effect of the
      macrolides tilmicosin and tylosin, which are only used in the veterinary clinic,
      on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and cytokines
      by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse peripheral
      blood mononuclear cells (PBMCs). Compared with 5 microg/mL, tilmicosin and
      tylosin concentrations of 10 microg/mL and 20 microg/mL significantly decreased
      the production of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), PGE(2),
      NO, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6,
      and increased IL-10 production. Cyclooxygenase-2 (COX-2) and inducible nitric
      oxide synthase (iNOS) gene expression were also significantly reduced. These
      results support the opinion that macrolides may exert an anti-inflammatory effect
      through modulating the synthesis of several mediators and cytokines involved in
      the inflammatory process.

PMID- 16647841
TI  - Antibiotic resistance in the cultivable plaque microbiota of children from
      different ethnic groups.
AB  - The presence of ampicillin-, penicillin-, erythromycin- and tetracycline
      resistant bacteria in the dental plaque of White, South Asian and Japanese
      children was investigated. There was a high prevalence of antibiotic-resistant
      bacteria in children from diverse ethnic groups. The median percentage of the
      cultivable plaque microbiota that was resistant to tetracycline was greater in
      South Asian (2.9%, range 0.1-17.5%) and Japanese (7.7%, range 1.3-56.2%) children
      than in White children (0.7%, range 0-5.6%), suggesting that ethnic differences
      exist in the oral load of tetracycline-resistant bacteria (P<0.01).
      Multiresistant bacteria were frequently isolated, with 42% of isolates exhibiting
      resistance to two or more antibiotics. This study has demonstrated that
      antibiotic-resistant bacteria can be readily isolated from the plaque microbiota
      of children from different ethnic groups.

PMID- 16647842
TI  - Prevalence and antimicrobial susceptibility patterns among gastroenteritis
      causing pathogens recovered in Europe and Latin America and Salmonella isolates
      recovered from bloodstream infections in North America and Latin America: report
      from the SENTRY Antimicrobial Surveillance Program (2003).
AB  - Gastroenteritis-causing pathogens are the second leading cause of morbidity and
      mortality worldwide. Complicating the clinical diarrhoea syndrome is the
      emergence of antimicrobial resistance among the responsible bacterial pathogens.
      The reported increases in fluoroquinolone resistance in Salmonella, Shigella and
      Campylobacter have been extremely worrisome considering the primary role of
      ciprofloxacin as a treatment. In this study, 1479 bacterial isolates from
      gastroenteritis infections were collected in Europe and Latin America, which
      included Salmonella spp. (834; 56%), Shigella spp. (311; 21%), Campylobacter spp.
      (182; 12%) and Aeromonas spp. (72; 5%). The fluoroquinolones displayed the
      greatest activity against these pathogens, with only three non-Campylobacter spp.
      strains being non-susceptible using current Clinical and Laboratory Standards
      Institute (CLSI) breakpoint criteria. Whilst ciprofloxacin resistance in European
      and Latin American Salmonella was only 0.2% and 0.0%, respectively, a total of
      16.2% and 12.9% of isolates were resistant to nalidixic acid, indicating possible
      first-step gyrA mutations. Among confirmed extended-spectrum beta-lactamase
      producing Salmonella strains, CTX-M genes were detected in 15 originating from
      Russia. Erythromycin and azithromycin were the most potent agents tested against
      Campylobacter spp. (values of minimum inhibitory concentration for 90% of the
      organisms, 0.5 mg/L and 0.12 mg/L, respectively), with erythromycin displaying
      the highest susceptibility (91.1%). Salmonella isolates from bloodstream
      infections displayed antibiograms that were nearly identical to strains causing
      gastroenteritis. Considering the role that antimicrobial therapy plays in the
      management of moderate to severe bacterial gastroenteritis, global surveillance
      and local/national public health programmes can provide critical data
      illuminating the dissemination of resistance and guidance for empirical therapy.

PMID- 16647843
TI  - Sex determination and sex reversal.
AB  - Sex determination in mammals is based on a genetic cascade that controls the fate
      of the gonads. Gonads will then direct the establishment of phenotypic sex
      through the production of hormones. Different types of sex reversal are expected
      to occur if mutations disrupt one of the three steps of gonadal differentiation:
      formation of the gonadal primordia, sex determination, and testis or ovary
      development.

PMID- 16647844
TI  - Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how
      aneuploidy causes meiotic errors.
AB  - As a group, sex chromosome aneuploidies - the 47,XXY, 47,XYY, 47,XXX and 45,X
      conditions - constitute the most common class of chromosome abnormality in human
      live-births. Considerable attention has been given to the somatic abnormalities
      associated with these conditions, but less is known about their meiotic
      phenotypes; that is, how does sex chromosome imbalance influence the meiotic
      process. This has become more important with the advent of assisted reproductive
      technologies, because individuals previously thought to be infertile can now
      become biological parents. Indeed, there are several recent reports of successful
      pregnancies involving 47,XXY fathers, and suggestions that cryopreservation of
      ovarian tissue might impart fertility to at least some Turner syndrome
      individuals. Thus, the possible consequences of sex chromosome aneuploidy on
      meiotic chromosome segregation need to be explored.

PMID- 16647845
TI  - Genomic and epigenomic approaches to the study of X chromosome inactivation.
AB  - X chromosome inactivation represents a compelling example of chromosome-wide,
      long-range epigenetic gene-silencing in mammals. The cis- and trans-acting
      factors that establish and maintain the patterns and levels of gene expression
      from the active and inactive X chromosomes remain incompletely understood;
      however, the availability of the complete genomic sequence of the human X
      chromosome, together with complementary approaches that explore the computational
      biology, epigenetic modifications and gene expression-profiling along the
      chromosome, suggests that the features of the X chromosome that are responsible
      for its unique forms of gene regulation are increasingly amenable to experimental
      analysis.

PMID- 16647846
TI  - NEMO, NFkappaB signaling and incontinentia pigmenti.
AB  - The identification of mutations in the NEMO gene in humans with incontinentia
      pigmenti and several other genetic conditions has led to an appreciation of the
      multiple roles of signaling through the NFkappaB pathway, and how erroneous
      signalling contributes to disease. The finding that the disease results from a
      common, recurrent mutation was surprising given the high variability in patients'
      phenotypes and illustrates the role of X inactivation and selection in females.
      Recent advances in mouse models and in understanding the multiple roles of NEMO
      in the cell provide additional avenues to define the various roles of NEMO in
      NFkappaB signaling.

PMID- 16647847
TI  - Transcription, translation and fragile X syndrome.
AB  - The fragile X mental retardation protein (FMRP) plays a role in the control of
      local protein synthesis in the dendrites. Loss of its production in fragile X
      syndrome is associated with transcriptional dysregulation of the gene. Recent
      work demonstrates that Sp1 and NRF1 transcriptionally control this gene. Other
      studies reveal how the microRNA pathway and signaling are related to FMRP
      function through the metabotropic glutamate receptor. These studies provide new
      insights through which we can better understand the inactivation of the FMR1 gene
      and, in turn, the consequence of FMRP loss.

PMID- 16647848
TI  - MeCP2 dysfunction in Rett syndrome and related disorders.
AB  - Rett syndrome, a neurodevelopmental disorder caused by mutations in the X-linked
      gene encoding methyl-CpG-binding protein 2 (MeCP2), is a leading cause of mental
      retardation with autistic features in females. MECP2 mutations have also been
      identified in individuals with a variety of clinical syndromes, including mild
      learning-disability in females, neonatal encephalopathy in males, and psychiatric
      disorders, autism and X-linked mental retardation in both males and females.
      Furthermore, MECP2 duplications have been shown to cause a progressive postnatal
      neurological disorder. MeCP2 is a transcriptional repressor that binds to
      methylated CpG dinucleotides flanked by AT-rich segments and recruits a co
      repressor complex, thereby altering chromatin structure. Subtle gene expression
      changes have been identified in Rett patients and mouse models; however, MeCP2
      dysfunction has also been shown to cause abnormalities of RNA splicing,
      suggesting a complex molecular pathogenesis. Discovering which genes are
      misregulated in the absence of functional MeCP2 and demonstrating their role in
      causing neuronal dysfunction and disease manifestations are challenging but
      important steps for understanding the pathogenesis of Rett syndrome and related
      disorders.

PMID- 16647849
TI  - Genetics of variation in human color vision and the retinal cone mosaic.
AB  - Variation in human color vision is mainly caused by one common polymorphism
      (Ser180Ala) in the L pigment, and to the frequent presence of hybrid genes that
      encode pigments with various spectral properties. Both recombination and gene
      conversion between the highly homologous L and M pigment genes have generated
      wide variation in genotype and color vision phenotype. The S, M and L cones are
      distributed randomly in the central retina. Unlike S cones, M and L cones vary
      widely in number within the central retina. Determining the number of the three
      classes of cone and their special distribution in the living retina has
      significantly advanced the ability to correlate the cone mosaic in normal and
      color-defective subjects with the color vision phenotype. The transcription
      factors NR2E3, TRbeta2 and RXRgamma play crucial roles in establishment of the
      retinal cone mosaic during eye development.

PMID- 16647850
TI  - X-linked mental retardation: many genes for a complex disorder.
AB  - X-linked mental retardation (XLMR) is a common cause of moderate to severe
      intellectual disability in males. XLMR is very heterogeneous, and about two
      thirds of patients have clinically indistinguishable non-syndromic (NS-XLMR)
      forms, which has greatly hampered their molecular elucidation. A few years ago,
      international consortia overcame this impasse by collecting DNA and cell lines
      from large cohorts of XLMR families, thereby paving the way for the systematic
      study of the molecular causes of XLMR. Mutations in known genes might already
      account for 50% of the families with NS-XLMR, and various genes have been
      pinpointed that seem to be of particular diagnostic importance. Eventually, even
      therapy of XLMR might become possible, as suggested by the unexpected plasticity
      of the neuronal wiring in the brain, and the recent successful drug treatment of
      a fly model for fragile X syndrome.

PMID- 16647851
TI  - Random X-chromosome inactivation: skewing lessons for mice and men.
AB  - The mammalian X-chromosome exists in two flavors, active and inactive, in each
      cell of the adult female. This phenomenon originates from the process of random
      choice occurring early in development in a small number of progenitor cells in
      which the decision is made to inactivate either one or the other X chromosome on
      a cell-autonomous basis. Once made, this initial decision is irreversible,
      although exceptions exist in specific chromosomal territories and cell lineages.
      Recent findings implicate various factors, including non-coding RNAs and
      chromatin modification complexes, as effectors in the initiation and maintenance
      of X-chromosome inactivation. The functional redundancy of such factors almost
      certainly plays an important role in the stability of the inactive X. Studying
      skewing or bias opens an important opportunity for understanding facets of the
      random choice process.

PMID- 16647852
TI  - Optimization studies on acid hydrolysis of oil palm empty fruit bunch fiber for
      production of xylose.
AB  - Oil palm empty fruit bunch fiber is a lignocellulosic waste from palm oil mills.
      It is a potential source of xylose which can be used as a raw material for
      production of xylitol, a high value product. The increasing interest on use of
      lignocellulosic waste for bioconversion to fuels and chemicals is justifiable as
      these materials are low cost, renewable and widespread sources of sugars. The
      objective of the present study was to determine the effect of H(2)SO(4)
      concentration, reaction temperature and reaction time for production of xylose.
      Batch reactions were carried out under various reaction temperature, reaction
      time and acid concentrations and Response Surface Methodology (RSM) was followed
      to optimize the hydrolysis process in order to obtain high xylose yield. The
      optimum reaction temperature, reaction time and acid concentration found were 119
      degrees C, 60 min and 2%, respectively. Under these conditions xylose yield and
      selectivity were found to be 91.27% and 17.97 g/g, respectively.

PMID- 16647853
TI  - Increase of oxidized/total coenzyme Q-10 ratio in cerebrospinal fluid in patients
      with Parkinson's disease.
AB  - The concentrations of oxidized coenzyme Q-10 (CoQ-10) and reduced CoQ-10 in the
      cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) was examined
      in order to determine whether the balance in oxidized and reduced CoQ-10 is
      related to the pathogenesis of PD. The percentage of oxidized/total CoQ-10 (%CoQ
      10) in the CSF was significantly higher in the untreated PD group (80.3+/-17.9%)
      compared to the normal control group (68.2+/-20.4%) (p<0.05). The %CoQ-10 in the
      CSF of PD patients showed significant negative correlation with the duration of
      illness. These findings in living patients provide in vivo evidence for a
      possible role for %CoQ-10 in the pathogenesis in the early stages of PD
      development.

PMID- 16647854
TI  - Effect of valproic acid on withdrawal therapy in patients with overuse of chronic
      daily headache medications.
AB  - Discontinuation of medication is the treatment of choice for patients with
      chronic daily headache (CDH) who overuse their medications. This treatment may be
      difficult due to increased headache severity observed in patients immediately
      after withdrawal. We retrospectively evaluated the efficacy of valproic acid
      therapy in 66 patients with overuse of CDH medication during withdrawal therapy.
      Patients were all withdrawn from medications and valproic acid started at 250 mg
      or 500 mg daily. Forty-two (63.6%) patients had decreased headache severity,
      including 27.3% objective responses in the first week. At the last visit in the
      12th week, 50 patients were headache-free and only one patient had persistent
      headache. Fifteen patients withdrew from therapy due to side effects and lost to
      follow-up within this timeframe. Thus, low dose valproic acid appears to be safe
      and effective in the management of withdrawal therapy.

PMID- 16647855
TI  - Sporadic encephalitis lethargica.
AB  - Three women (aged 21-36 years) developed acute illnesses that were similar to
      epidemic encephalitis lethargica. Each presented with a neuropsychiatric
      disturbance that was succeeded by pyrexia, a fluctuating conscious state and
      involuntary movements including oculogyria. Cerebrospinal fluid examination
      showed a predominantly lymphocytic pleocytosis (64-120x10(6) cells/L) and
      oligoclonal bands were detected in two cases. Two patients died, while the third
      made a gradual recovery. Post-mortem examination in the two fatal cases showed
      changes of lymphocytic meningitis and focal diencephalic lymphocytic
      infiltration, although these changes were mild relative to the effects of the
      clinical illness. The diagnosis of sporadic encephalitis lethargica relies on
      identifying shared clinical features with the past epidemic disease plus
      circumstantial evidence of immunological activity from laboratory investigations
      and some tests of exclusion of other disorders.

PMID- 16647856
TI  - Cerebrospinal fluid spectrophotometry of bilirubin, not the Xanthochromic Index,
      for the detection of CT-negative sub-arachnoid haemorrhage.

PMID- 16647857
TI  - Ubiquitin and SUMO systems in the regulation of mitotic checkpoints.
AB  - Proteolysis mediated by the ubiquitin-proteasome system is a crucial regulatory
      mechanism in signal transduction cascades of temporal cellular processes such as
      cell division. Two principal subtypes of modular ubiquitin ligase, the anaphase
      promoting complex or cyclosome (APC/C) and the Skp1/Cullin-1/F-box protein
      complex, have emerged as essential regulators of key events in the cell cycle.
      The importance of these ligases is best illustrated by their roles in the
      checkpoint and repair pathways or in response to multiple stresses, where they
      affect activation of the M-phase-promoting factor or proper formation and/or
      maintenance of the mitotic spindle. Recent studies have considerably improved our
      understanding of the function of the concerted action of the phosphorylation and
      ubiquitin or SUMO systems in the regulation of the stability and activity of key
      components of the mitotic checkpoint.

PMID- 16647858
TI  - How a single protein complex accommodates many different H/ACA RNAs.
AB  - More than 100 mammalian H/ACA RNAs form an equal number of ribonucleoproteins
      (RNPs) by associating with the same four core proteins. The function of these
      H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor
      mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular
      processes. Recent crystal structures of archaeal H/ACA protein complexes show how
      the same four proteins accommodate >100 distinct but related H/ACA RNAs and
      reveal that a spatial mutation cluster underlies dyskeratosis congenita, a
      syndrome of bone marrow failure.

PMID- 16647859
TI  - Changes in the cell-wall polysaccharides of outer pericarp tissues of kiwifruit
      during development.
AB  - Changes in pectin, hemicelluloses and cellulose in the cell walls of outer
      pericarp tissues of kiwifruit (Actinidia deliciosa cv. Hayward) were determined
      during development. An extensive amylase digestion was employed to remove
      possible contaminating starch before and after fractionation of wall
      polysaccharides. An initial treatment of crude cell walls with alpha-amylase and
      iso-amylase or DMSO, was found to be insufficient removing the contaminating
      starch from wall polysaccharides. After EDTA and alkaline extraction, the pectic
      and hemicellulose fractions were again treated with the combination of alpha
      amylase and iso-amylase. The amounts of predominant pectic sugars Gal, Rha and
      Ara, unaffected by the first and second amylase digestion, decreased markedly
      during the early fruit enlargement (8-12 weeks after anthesis, WAA), then
      increased during 16-20 WAA, and finally declined during fruit maturity (20-25
      WAA). The molecular-mass of pectic polysaccharides decreased during fruit
      enlargement (8-16 WAA), and then changed little during fruit maturity. The higher
      molecular-mass components of hemicelluloses in HC-I and HC-II fractions detected
      at the early stage of fruit enlargement (8-12 WAA) were degraded at the late
      stage of fruit enlargement (16 WAA), but then remained stable at the much lower
      molecular-mass till fruit maturity. The amount of Xyl in the HC-II fraction
      decreased during the early fruit enlargement and fruit maturity, an observation
      that was consistent with xyloglucan (XG) content. The gel permeation profiles of
      XG showed a slight increase in higher molecular-mass components during 8-12 WAA,
      but thereafter there was no significant down-shift of molecular-mass until
      harvest time. The cellulose fraction increased steadily during fruit enlargement
      through maturity, but the XG contents in HC-I and HC-II fractions remained at a
      low level during these stages. Methylation analysis of HC-I and HC-II fractions
      confirmed the low level of XG in the hemicellulosic fractions. It was suggested
      that pectin in the outer pericarp of kiwifruit was degraded at the early stage of
      fruit enlargement, but XG remains constant during fruit enlargement and
      maturation.

PMID- 16647860
TI  - Antioxidant properties of recombinant allophycocyanin expressed in Escherichia
      coli.
AB  - Allophycocyanin (APC) is the main core component of phycobilisome found in blue
      green algae. The apo-allophycocyanin and its subunits were expressed in
      Escherichia coli and their antioxidant properties were evaluated using
      deoxyribose assay. The result showed that both recombinant allophycocyanin fused
      with maltose binding protein (MBP) tag and 6 x His-tag and their alpha or beta
      subunits can scavenge hydroxyl radicals successfully, and the separated alpha or
      beta subunits had a higher inhibition effect on hydroxyl radicals than that when
      they combined together. The scavenging effects increased with the increasing
      concentration. These results clearly suggested that apo-allophycocyanin is
      involved in the antioxidant and radical scavenging activity of phycocyanin, and
      the antioxidant activity may be partially responsible to the anti-tumor effect of
      the recombinant allophycocyanin.

PMID- 16647861
TI  - Expression and characterization of a housefly cecropin gene in the methylotrophic
      yeast, Pichia pastoris.
AB  - A 371 bp full-length cDNA (GenBank Accession No. DQ232774) was obtained from
      housefly Musca domestica by using degenerate primers and subsequent amplification
      by 5'- and 3'-RACE. The cecropin gene, Mdcec and Mdcec/6His, was cloned into
      expression pPICZalpha-A vector and was expressed in the methylotrophic yeast,
      Pichia pastoris. The recombinant Mdcec was purified using cationic exchange
      chromatography and 1.2mg pure active Mdcec was obtained from 100ml culture broth
      supernatant. To facilitate purification of Mdcec, the C-terminal 6His-tagged
      Mdcec was also expressed in P. pastoris. The recombinant Mdcec/6His was purified
      to homogeneity by a nickel chelating sepharose column and 2.0mg pure active
      Mdcec/6His was obtained from 100ml culture broth supernatant. Anti-microbial
      assays demonstrated that Mdcec had broad spectrum of antimicrobial property
      against fungi, as well as Gram-positive and Gram-negative bacteria. Mdcec/6His
      showed a similar activity to Mdcec against bacteria, but a slight higher activity
      against fungi. These results indicate that the 6His-tag can enhance the cationic
      nature and stability of Mdcec. This is the first report on the heterologous
      expression of a cecropin and cecropin with a 6His tag in P. pastoris. Our results
      suggest that the P. pastoris expression system can be used to produce large
      quantities of fully functional M. domestica cecropin for both research and
      industrial purpose.

PMID- 16647862
TI  - Intensity inhomogeneity correction of multispectral MR images.
AB  - Intensity inhomogeneity in MR images is an undesired phenomenon, which often
      hampers different steps of quantitative image analysis such as segmentation or
      registration. In this paper, we propose a novel fully automated method for
      retrospective correction of intensity inhomogeneity. The basic assumption is that
      inhomogeneity correction could be improved by integrating spatial and intensity
      information from multiple MR channels, i.e., T1, T2, and PD weighted images.
      Intensity inhomogeneities of such multispectral images are removed simultaneously
      in a four-step iterative procedure. First, the probability distribution of image
      intensities and corresponding spatial features is calculated. In the second step,
      intensity correction forces that tend to minimize joint entropy of multispectral
      image are estimated for all image voxels. Third, independent inhomogeneity
      correction fields are obtained for each channel by regularization and
      normalization of voxel forces, and last, corresponding partial inhomogeneity
      corrections are performed separately for each channel. The method was
      quantitatively evaluated on simulated and real MR brain images and compared to
      three other methods.

PMID- 16647863
TI  - Are fMRI event-related response constant in time? A model selection answer.
AB  - An accurate estimation of the hemodynamic response function (HRF) in functional
      magnetic resonance imaging (fMRI) is crucial for a precise spatial and temporal
      estimate of the underlying neuronal processes. Recent works have proposed non
      parametric estimation of the HRF under the hypotheses of linearity and
      stationarity in time. Biological literature suggests, however, that response
      magnitude may vary with attention or ongoing activity. We therefore test a more
      flexible model that allows for the variation of the magnitude of the HRF with
      time in a maximum likelihood framework. Under this model, the magnitude of the
      HRF evoked by a single event may vary across occurrences of the same type of
      event. This model is tested against a simpler model with a fixed magnitude using
      information theory. We develop a standard EM algorithm to identify the event
      magnitudes and the HRF. We test this hypothesis on a series of 32 regions (4 ROIS
      on eight subjects) of interest and find that the more flexible model is better
      than the usual model in most cases. The important implications for the analysis
      of fMRI time series for event-related neuroimaging experiments are discussed.

PMID- 16647864
TI  - Phylogenetic significance of morphological characters in the tropical
      Hypotrachyna clade of parmelioid lichens (Parmeliaceae, Ascomycota).
AB  - Lichen-forming ascomycetes exhibit often complex morphologies of the vegetative
      thallus that are usually not found in non-lichenized fungi. This includes the
      thallus organization and appendical structures associated with the main thallus,
      such as cilia and rhizines. Such morphological characters are widely employed in
      the taxonomy of parmelioid lichens, especially at generic level. Within
      parmelioid lichens, several monophyletic groups can be distinguished, the
      Hypotrachyna clade being one of them, which includes mostly tropical taxa. In
      this first molecular study focused specifically on the Hypotrachyna clade, we
      used maximum parsimony and Bayesian analyses of a combined data set of nuclear
      ITS and mitochondrial SSU rDNA sequences to (1) test the monophyly of genera
      presently accepted within the clade and (2) evaluate the phylogenetic value of
      the morphological characters used to circumscribe genera in parmelioid lichens.
      Out of the 89 mtSSU and 88 nuITS sequences included in the present study, 121
      sequences were newly obtained. Our results show that the taxa within the clade
      fall into two major groups and that the genus Hypotrachyna is polyphyletic.
      Everniastrum and Parmelinopsis are nested within Hypotrachyna sensu stricto, the
      latter being also polyphyletic. Bulbothrix is paraphyletic with Parmelinella
      nested within and is basal to the second major Hypotrachyna clade. Monophylies of
      Bulbothrix and Hypotrachyna are significantly rejected. The phylogenetic analysis
      demonstrates that morphological characters currently used to circumscribe genera
      in parmelioid lichens, such as cortical anatomy, lobe configuration, cilia, and
      rhizines have been overestimated and have only minor value in identifying
      monophyletic groups.

PMID- 16647865
TI  - Phylogenetic utility of indels within ribosomal DNA and beta-tubulin sequences
      from fungi in the Rhizoctonia solani species complex.
AB  - The genus Rhizoctonia consists of a diverse assemblage of anamorphic fungi
      frequently associated with plants and soil throughout the world. Some anamorphs
      are related with teleomorphs (sexual stage) in different taxonomic classes,
      orders, and families. The fungus may exist as pathogen, saprophyte, or
      mycorrhizal symbiont and shows extensive variation in characteristics such as
      geographic location, morphology, host specificity, and pathogenicity. In this
      study, phylogenetic analyses were performed in the Rhizoctonia solani species
      complex with individual and combined data sets from three gene partitions (ITS,
      LSU rDNA, and beta-tubulin). To explore whether indels were a source of
      phylogenetically informative characters, single-site indels were treated as a new
      state, while indels greater than one contiguous nucleotide were analyzed by
      including them as ambiguous data (Coding A); excluding them from the analyses
      (Coding B), and with three distinct codes: multistate for different sequence
      (Coding C); multistate for different length (Coding D) and different characters
      for each distinct sequence (Coding E). Results suggest that indels in noncoding
      regions contain phylogenetic information and support the fact that the R. solani
      species complex is not monophyletic. Six clades within R. solani
      (teleomorph=Thanatephorus) representing distinct anastomosis groups and five
      clades within binucleate Rhizoctonia (teleomorph=Ceratobasidium) were well
      supported in all analyses. The data suggest that clades with representatives of
      R. solani fungi belonging to anastomosis groups 1, 4, 6, and 8 should be
      recognized as phylogenetic species.

PMID- 16647866
TI  - The orphan G-protein coupled receptor RDC1: evidence for a role in chondrocyte
      hypertrophy and articular cartilage matrix turnover.
AB  - OBJECTIVE: RDC1 is a class A orphan G-protein coupled receptor of unknown
      function. The purpose of this study was to identify compound RDC1 agonists and
      use these as tools to determine the effect of RDC1 activation in human
      chondrocytes and cartilage explant tissue. METHODS: Computational chemistry was
      employed to build a homology model of the RDC1 receptor. A virtual screen of in
      house compounds was then performed and positive hits screened for their ability
      to invoke a Ca2+ response in a recombinant RDC1 HEK293 cell line, as measured by
      FLIPR. The effect of RDC1 activation on human chondrocytes and cartilage explant
      gene expression was determined by quantitative real-time polymerase chain
      reaction (PCR), and these effects validated as being mediated by RDC1 using siRNA
      antisense. RESULTS: Tissue expression profiling demonstrated that RDC1 expression
      was predominant in cartilage tissue. Treatment of human primary chondrocytes with
      RDC1 agonist induced a Ca2+ response, suggesting the receptor is active in this
      tissue type. Treatment for 24h with RDC1 agonist led to altered expression of a
      number of genes associated with chondrocyte hypertrophy and increased matrix
      degradation in human primary chondrocytes, and elevated total matrix
      metalloproteinase (MMP) activity in cartilage explant. Transfection with RDC1
      siRNA caused a >90% reduction in human primary chondrocyte RDC1 expression and
      significantly reduced the impact of RDC1 agonist on the previously identified
      RDC1-regulated genes. CONCLUSIONS: RDC1 activation in human chondrocytes and
      cartilage explant leads to changes in gene expression and activity associated
      with chondrocyte hypertrophy, angiogenesis and increased matrix degradation,
      suggesting signalling via the RDC1 receptor may play an important role in the
      early development of osteoarthritis (OA).

PMID- 16647867
TI  - Retinoic acid-induced protein ISGylation is dependent on interferon signal
      transduction.
AB  - Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier that forms
      conjugates with target protein substrates. As its name suggests, its expression
      and conjugation to other proteins are highly regulated by interferon (IFN). It
      was recently demonstrated that ISG15 expression, ISG15 conjugation, and several
      enzymes involved in ISG15 modification are upregulated in an acute promyelocytic
      cell line following treatment with retinoic acid, suggesting a possible retinoic
      acid induced IFN-independent ISG15 modification pathway. In this study, we
      examined a possible link between IFN signaling and retinoic acid-induced ISG15
      conjugation. We observed that ISGylation can be induced by retinoic acid in two
      myeloid leukemia cell lines. By sandwich ELISA, we detected increased IFN
      secretion into cell culture media following retinoic acid treatment. Blockade of
      the type I IFN receptor with a neutralizing antibody blocked retinoic acid
      induced ISG15 expression and ISG15 conjugation. Taken together, these data
      suggested that retinoic acid-induced secretion of IFN plays a fundamental role in
      retinoic acid promoted ISGylation.

PMID- 16647869
TI  - Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in
      immune cells: implications for immunity, autoimmune diseases, and apoptosis.
AB  - Nitric oxide plays a central role in the physiology and pathology of diverse
      tissues including the immune system. It is clear that the levels of nitric oxide
      must be carefully regulated to maintain homeostasis. Appropriate levels of nitric
      oxide derived from iNOS assist in mounting an effective defense against invading
      microbes. Conversely, inability to generate nitric oxide results in serious, even
      fatal, susceptibility to infections. Further, dysregulation or overproduction of
      nitric oxide has been implicated in the pathogenesis of many disorders, including
      atherosclerosis, neurodegenerative diseases, inflammatory autoimmune diseases,
      and cancer. Therefore, depending upon the levels of nitric oxide generated, the
      potential exists for nitric oxide to behave like a "double-edged" biological
      sword. Taking these issues into consideration, it is thus pivotal to understand
      the regulation of nitric oxide. Nitric oxide is regulated by many endogenous
      factors including hormones such as estrogens. While the effects of estrogen on
      the generation of nitric oxide in non-immune tissues are relatively well
      documented, the effect of estrogen on iNOS/nitric oxide in immune cells is only
      now becoming apparent. Our laboratory has recently shown that estrogen treatment
      of mice markedly upregulates the levels of iNOS mRNA, iNOS protein, and nitric
      oxide in activated splenocytes. This upregulation of nitric oxide is in part
      mediated through interferon-gamma (IFN-gamma), a pro-inflammatory cytokine that
      is enhanced by estrogen. These findings are important considering that estrogens
      are not only involved in regulation of normal immune responses, but also are
      implicated in many autoimmune and inflammatory diseases. To date, there are no
      reviews on the effects of estrogen on immune tissue-derived nitric oxide and
      therefore this review will address this critical gap in the literature. Given the
      increasing importance of immune-tissue-derived iNOS in health and disease,
      studies on estrogen-induced regulation of iNOS may offer a better understanding
      of diseases and aid in devising new therapeutic interventions.

PMID- 16647868
TI  - Nitric oxide decreases the stability of DMPO spin adducts.
AB  - The effect nitric oxide (NO*) on the stability of 5,5-dimethyl-1-pyrroline-N
      oxide (DMPO) adducts has been investigated using EPR spectroscopy. We report that
      the DMPO/HO* adduct, generated by porcine pulmonary artery endothelial cells in
      the presence of H2O2 and DMPO, or by a Fenton system (Fe(II)+H2O2) is degraded in
      the presence of the NO*-donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO)
      or by bolus addition of an aqueous solution of NO*. A similar effect of DEANO was
      observed on other DMPO adducts, such as DMPO/*CH3 and DMPO/*CH(CH3)OH, generated
      in cell-free systems. Measurements of the loss of DMPO/HO* in the presence of
      DEANO in aerated and oxygen-free buffers showed that in both of these settings
      the process obeys first-order kinetics and proceeds with similar efficacy. This
      indicates that direct interaction of the nitroxide with NO*, rather than with
      NO2* (formed from NO* and O2 in aerated media), is responsible for destruction of
      the spin adduct. These results suggest that the presence of NO* may substantially
      affect the quantitative determination of DMPO adducts. We also show that NO2*
      radicals, generated by a myeloperoxidase/H2O2/nitrite system, also degrade
      DMPO/HO*. Because DMPO is frequently used to study generation of superoxide and
      hydroxyl radicals in biological systems, these observations indicate that extra
      caution is required when studying generation of these species in the presence of
      NO* or NO2* radicals.

PMID- 16647870
TI  - Randomised double-blind, positive-controlled trial to assess the efficacy of
      glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis.
AB  - Thirty-five dogs were included in a randomised, double-blind, positive
      controlled, multi-centre trial to assess the efficacy of an orally-administered
      glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the
      treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a
      positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of
      treatment. Medication was then withdrawn and dogs were re-assessed on day 98.
      Response to treatment was based on subjective evaluation by participating
      veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS
      showed statistically significant improvements in scores for pain, weight-bearing
      and severity of the condition by day 70 (P<0.001). Onset of significant response
      was slower for Glu/CS than for carprofen-treated dogs. The results show that
      Glu/CS has a positive clinical effect in dogs with osteoarthritis.

PMID- 16647871
TI  - A six-year study on respiratory viral infections in a bull testing facility.
AB  - Viral infection dynamics and bovine respiratory disease (BRD) treatment rates
      were studied over six years at a Swedish bull testing station with an 'all in,
      all out' management system. In August of each of the years 1998-2003, between 149
      and 185 4-8-month-old calves arrived at the station from 99 to 124 different beef
      breeding herds, and remained until March the following year. Only calves that
      tested free from bovine viral diarrhoea virus (BVDV) were allowed to enter the
      station and original animal groups were kept isolated from new cattle in their
      original herds for three weeks before admission. Although neither prophylactic
      antibiotics, nor BRD vaccines were used, less than 0.7-13.2% (mean 5%) of the
      calves (n=970) required treatment for BRD during the first five weeks following
      entry. This was probably due, at least in part, to the season (the summer months)
      when the animals were commingled. In the six-month period August-February, 38% of
      the animals were treated one or more times for BRD and mortality was 0.7%.
      Hereford and Aberdeen Angus calves had significantly higher treatment rates than
      Charolais, Simmental and Blonde d'Aquitaine. Serological testing on samples
      obtained in August, November and January indicated that bovine parainfluenza
      virus 3 (PIV-3) infections occurred each year before November after entry. Bovine
      coronavirus (BCoV) infections also occurred every year, but in 3/6 years this was
      not until after November. Bovine respiratory syncytial virus (BRSV) infections
      occurred only every second year and were associated with a treatment peak and one
      death on one occasion (December). The herd remained BVDV free during the entire
      study period. The infection patterns for PIV-3 and BCoV indicated a high level of
      infectivity amongst bovine calves, whereas the incidence for BRSV was observed at
      a lower level. Although the rearing of the animals differed from conventional
      beef production, the study has shown that commingling animals from many sources
      is not necessarily associated with high morbidity within the first few weeks
      after arrival. By preventing BRD soon after commingling the prerequisites for
      protective vaccination at entry might be improved. Applied management routines
      are discussed.

PMID- 16647872
TI  - Pituitary, adrenal, immune and performance responses of mature Holstein x
      Friesian bulls housed on slatted floors at various space allowances.
AB  - The effect of various space allowances on the pituitary, adrenal and immune
      responses and on performance was investigated in 72 mature Holstein x Friesian
      beef bulls. The animals (weighing 403+/-3.5 kg) were blocked by weight and
      randomly assigned to two groups (familiar, F, and unfamiliar, UF) x three
      treatments (1.2, 2.7 and 4.2m(2) per bull; n=24 per space allowance), and housed
      for 83 days in 18 pens (n=4 per pen). Blood samples were collected on days -1, 0,
      3, 14, 36 and 77 with respect to mixing and housing on day 0. The bulls were
      given exogenous adrenocorticotrophic hormone (ACTH) on day 3 and corticotrophin
      releasing hormone (CRH) on days 14, 36 and 77. Basal plasma cortisol
      concentration was not affected (P>0.05) by mixing F and UF bulls. On day 3, basal
      cortisol was greater (P<0.05) in bulls housed at 1.2 than those at 2.7 and
      4.2m(2) space allowances while no effect was observed in ACTH-induced plasma
      cortisol concentration among treatments. Following CRH administration, there was
      no effect (P>0.05) of treatment and treatment x time on plasma ACTH
      concentration. On day 14, interferon-gamma production was lower (P<0.05) in the
      bulls housed at 4.2 vs. 2.7 m(2) and was intermediate but not significantly
      different (P>0.05) for those housed at 1.2m(2). Animals housed at either space
      allowances had significant (P<0.05) neutrophilia, lymphopenia, eosinopenia and
      decreased haemoglobin on day 3 compared with day 0. The liveweight gain from days
      0 to 83 was lower (P<0.05) in bulls housed at 1.2 compared with those at 2.7 and
      4.2m(2). Housing bulls at 1.2m(2) space allowance had a detrimental effect on
      their growth and was associated with an acute rise in plasma cortisol
      concentration (on day 3) compared with those having space allowances of 2.7 and
      4.2m(2)/bull.

PMID- 16647873
TI  - Inhibition of ovarian development by methyl farnesoate in the tadpole shrimp,
      Triops longicaudatus.
AB  - Methyl farnesoate (MF), a putative crustacean hormone, is the immediate precursor
      of insect juvenile hormone III (JHIII) in the biosynthetic pathway. We examined
      whether MF, shown to inhibit adult metamorphosis in several crustacean species,
      is a juvenilizing factor in the tadpole shrimp, Triops longicaudatus. Oocyte
      production was chosen as a parameter for measuring reproductive development. MF
      was administered to juveniles by ingestion via biological vector (Artemia
      nauplii), MF-coated food pellets, and MF liposome food pellets. Artemia were
      incubated in 30 microl of 5 microg/ml MF. The MF-coated and MF liposome pellets
      were prepared with MF concentrations ranging between 0.1 microg/g and 10 microg/g
      MF by weight. Groups of tadpole shrimp were treated with these vectors from the
      time of hatching for 5 or 10 days in laboratory and field studies. The treatment
      groups of all the MF vectors showed reductions in oocyte production. Lower
      concentrations of MF (0.75 microg/g-3.8 microg/g MF) appeared to have a
      physiological effect on fecundity, but higher concentrations (10 microg/g MF)
      reduced somatic growth. MF-coated pellets (1 microg/g MF) administered to adults
      (after 5 days) caused no difference in oocyte production. The observed reductions
      of fecundity and the disparity of results between MF treatment on juveniles and
      adults suggest that MF may regulate ovarian development.

PMID- 16647874
TI  - Lipid composition of Ruditapes philippinarum spat: effect of ration and diet
      quality.
AB  - This study investigates the influence of the lipid composition of microalgal and
      commercial flour diets on the lipid classes and fatty acids of Ruditapes
      philippinarum spat. Aspects of the nutritional role of the diets and the feeding
      ration are discussed with regard to previously published spat growth data. Our
      results demonstrated that clams showed the best growth rates when fed with diets
      that supplied a larger quantity of lipids, further characterised by a high
      content of phospholipids and triacylglycerols. We observed a significant
      correlation between the amount of triacylglycerols (r=0.929, p<0.05) and
      phospholipids (r=0.781, p<0.05) supplied and spat growth. In addition, R.
      phillipinarum spat reached the highest percentages of triacylglycerols (about
      12%) and the lowest percentages of phospholipids (about 60%) and sterols (about
      4%) with these growth-promoting diets. Spat fed with the other diets and/or
      rations showed lower growth rates and significantly lower quantities of
      triacylglycerols. In the present study, the alternative essentiality of 20:5n-3
      and/or 22:6n-3 is confirmed. The diminishing supply of 22:6n-3 without an
      increase of 20:5n-3 has an effect on the growth of the spat. The dietary
      composition of fatty acids influenced the fatty acid profiles in bivalves. The
      results of our study would suggest that R. philippinarum is incapable of
      transforming 18:3n-3 to 20:5n-3 and then to 22:6n-3. Accordingly, although diets
      contained 18:3n-3, the spat reflected the low content of 20:5n-3 of the diets.
      With respect to 22:6n-3, given that this fatty acid is present in high quantities
      in Isochrysis, the spat content of this fatty acid was relative to its content in
      the diet. This study showed that clams with the lowest growth rates presented an
      increase in 20:4n-6. In the spat fed with the microalgal diets, 18:2n-6 scarcely
      reached 2% whereas in spat fed with wheat germ 18:2n-6 amounted to 18% of the
      total fatty acids. This fatty acid, by means of elongation, transforms to 20:2n
      6, which also appeared in important quantities in the lipids of the spat fed
      totally or partially by wheat germ. We note that 20:2n-6 did not originate from
      the diet since it is absent in the microalgae and the flour. The desaturation of
      20:2n-6 to 20:3n-6 has not been observed (low levels of 20:3n-6 in all cases) and
      therefore it can be assumed that the observed levels of 20:4n-6 were diet
      related.

PMID- 16647875
TI  - The TOR signalling network from yeast to man.
AB  - The target of rapamycin, TOR, is an essential ser/thr protein kinase that
      functions in two distinct multiprotein complexes, TOR complex 1 and 2. The
      structure and functions of these complexes have been conserved from yeast to man.
      TOR complex 1 is inhibited by rapamycin and is thought to couple growth cues to
      cellular metabolism; TOR complex 2 is not inhibited by rapamycin and appears to
      regulate spatial aspects of growth such as cell polarity. Work done in a variety
      of model systems, continues to contribute to our current understanding of this
      TOR signalling network. Recent studies in flies and mammalian tissue culture
      cells have elucidated many signalling components upstream of TOR complex 1. These
      studies also suggest that aberrant mammalian TOR complex 1 signalling contributes
      to a number of pathologies ranging from metabolic diseases to hyperproliferative
      disorders and cancers. Consequently the efficacies of rapamycin and related
      compounds in treating such diseases are being evaluated in clinical trials.

PMID- 16647876
TI  - Identifying asthma exacerbations in a pediatric emergency department: a
      feasibility study.
AB  - BACKGROUND: Asthma is a common pediatric chronic disease and is estimated to
      account for more than 2million emergency department visits per year. Asthma
      guidelines have demonstrated improved outcomes, but remain underutilized due to
      several barriers. Computerized methods to automatically identify asthma
      exacerbations may be beneficial to initiate guideline recommended treatment, but
      have not been described. The goal of the study was to examine the accuracy of an
      algorithm to identify asthma patients at triage in real-time using only
      electronically available data. METHODS: During a 9-month period, the five most
      frequent presenting chief complaints for Emergency Department asthma patients
      aged 2-18 years were identified and accounted for >95% of asthma visits:
      wheezing, shortness of breath, fever, cough, and dyspnea. During a following 1
      month period (November 2004), medical records of all patients with one of the
      five chief complaints were reviewed to establish a reference standard diagnosis.
      An asthma identification algorithm was developed that considered only data
      available in electronic format at the time of triage and included the presenting
      chief complaint, information from the computerized problem list (past medical
      history; current medications, such as beta-agonists, steroids, and other asthma
      medications), and ICD-9 billing codes from previous encounters. RESULTS: From
      1835 Emergency Department visits, 368 visits (154 with asthma) had one of the
      five chief complaints and were included. A problem list was available in 203
      (55.2%) and an ICD-9 code in 68 (18.5%) patients. Wheezing accounted for 56.5% of
      asthma visits, while fever was the most frequent chief complaint among all
      patients (43.8%). The asthma identification algorithm had a sensitivity of 44.8%
      (95% CI: 36.8-53.0%), a specificity of 91.6% (CI: 87.0-94.9%), a positive
      predictive value of 79.3% (CI: 69.3-87.3%) and a negative predictive value of
      69.8% (CI: 64.0-75.1%). The positive and negative likelihood ratios were 5.3 (CI:
      3.3-8.6) and 0.6 (CI: 0.5-0.7), respectively. CONCLUSION: The simple
      identification algorithm demonstrated good accuracy for identifying asthma
      episodes. The algorithm may represent a promising and feasible approach to create
      computerized reminders or automatic triggers that can facilitate the initiation
      of guideline-based asthma treatment in the Emergency Department.

PMID- 16647877
TI  - Remote consultations and HIV/AIDS continuing education in low-resource settings.
AB  - BACKGROUND: Telemedicine is a way to support physicians working in resource-poor
      settings, providing remote consultations and continuing medical education on
      HIV/AIDS care. METHODS: A hybrid E-mail/web support telemedicine service was
      created in 2003 at the Institute of Tropical Medicine, Antwerp, Belgium, with a
      discussion forum hosting more than 170 healthcare professionals from 40 different
      countries, generally resource constrained. Interesting posts and recurring
      questions from this discussion forum have been elaborated as case studies or
      frequently asked questions, available on the website for consultation. Education
      and support are also provided through interactive quizzes, user-friendly
      guidelines, and policy documents with a particular focus on HIV/AIDS care in
      developing countries. RESULTS: From April 2003 to March 2005, 342 questions were
      sent from over 17 countries in Africa, Asia, and South America. The vast majority
      of these questions (93%) were patient-oriented, with only 7% being general
      questions. Of the patient-oriented questions, 49% were related to antiretroviral
      therapy, and 44% were related to the diagnosis and treatment of opportunistic
      infections. CONCLUSIONS: Telemedicine is a cheap and effective method of
      providing clinical support and continuing education to healthcare workers
      treating HIV-positive patients in resource-poor settings.

PMID- 16647878
TI  - Towards patient-related information needs.
AB  - The quality of health care depends, among other factors, on the quality of a
      physician's domain knowledge. Since it is impossible to keep up with all new
      findings and developments, physicians usually have gaps in their domain
      knowledge. To handle exceptional cases, access to the full range of medical
      literature is required. The specific literature needed for appropriate treatment
      of the patient is described by a physician's information need. Physicians are
      often unaware of their information needs. To support them, this paper presents a
      first step towards automatically formulating patient-related information needs.
      We start investigating how we can model a physician's information needs in
      general. Then we propose an approach to instantiate the model into a
      representation of a physician's information needs using the patient data as
      stored in a medical record. Our experiments show that this approach is feasible.
      Since the number of formulated patient-related information needs is rather high,
      it has to be reduced. To reduce the number of formulated information needs we
      propose the use of additional knowledge. Four types of knowledge are discussed,
      viz. (a) knowledge about temporal aspects, (b) domain knowledge, (c) knowledge
      about a physician's specialism, and (d) a user model. Future research has to
      clarify which type of knowledge (or combination thereof) is most appropriate for
      our purpose. It is expected that the resultant set of information needs will have
      a manageable size and contributes to the quality of health care.

PMID- 16647879
TI  - Intracellular localization and tissue-specific distribution of human and yeast
      DHHC cysteine-rich domain-containing proteins.
AB  - Increasing evidence indicates that DHHC cysteine-rich domain-containing proteins
      (DHHC proteins) are protein acyltransferases. Although multiple DHHC proteins are
      found in eukaryotes, characterization has been examined for only a few. Here, we
      have cloned all the yeast and human DHHC genes and investigated their
      intracellular localization and tissue-specific expression. Most DHHC proteins are
      localized in the ER and/or Golgi, with a few localized in the plasma membrane and
      one in the yeast vacuole. Human DHHC mRNAs also differ in their tissue-specific
      expression. These results may provide clues to aid in discovering the specific
      function(s) of each DHHC protein.

PMID- 16647880
TI  - Molecular phylogeny of Cercomonadidae and kinetid patterns of Cercomonas and
      Eocercomonas gen. nov. (Cercomonadida, Cercozoa).
AB  - Cercomonads are among the most abundant and widespread zooflagellates in soil and
      freshwater. We cultured 22 strains and report their complete 18S rRNA sequences
      and light microscopic morphology. Phylogenetic analysis of 51 Cercomonas rRNA
      genes shows in each previously identified major clade (A, B) two very robust,
      highly divergent, multi-species subclades (A1, A2; B1, B2). We studied kinetid
      ultrastructure of five clade A representatives by serial sections. All have two
      closely associated left ventral posterior microtubular roots, an anterior dorsal
      root, a microtubule-nucleating left anterior root, and a cone of microtubules
      passing to the nucleus. Anterior centrioles (=basal bodies, kinetosomes) of A1
      have cartwheels; the posterior centriole does not, suggesting it is older, and
      implying flagellar transformation similar to other bikonts. Strain C-80 (subclade
      A2) differs greatly, having a dorsal posterior microtubule band, but lacking the
      A1-specific fibrillar striated root, nuclear extension to the centrioles,
      centriolar diaphragm, extrusomes; both mature centrioles lack cartwheels. For
      clade A2 we establish Eocercomonas gen. n., with type Eocercomonas ramosa sp. n.,
      and for clade B1 Paracercomonas gen. n. (type Paracercomonas marina sp. n.). We
      establish Paracercomonas ekelundi sp. n. for culture SCCAP C1 and propose a
      Cercomonas longicauda neotype and Cercomonas (=Neocercomonas) jutlandica comb. n.
      and Paracercomonas (=Cercomonas) metabolica comb. n.

PMID- 16647881
TI  - Translating m-AAA protease function in mitochondria to hereditary spastic
      paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a genetically heterogeneous
      neurodegenerative disorder that is characterized by progressive and cell-specific
      axonal degeneration. An autosomal recessive form of the disease is caused by
      mutations in paraplegin, which is a conserved subunit of the ubiquitous and ATP
      dependent m-AAA protease in mitochondria. The m-AAA protease carries out protein
      quality control in the inner membrane of the mitochondria, suggesting a
      pathogenic role of misfolded proteins in HSP. A recent study demonstrates that
      the m-AAA protease regulates ribosome assembly and translation within
      mitochondria by controlling proteolytic maturation of a ribosomal subunit. Here,
      we will discuss implications of the dual role of the m-AAA protease in protein
      activation and degradation for mitochondrial dysfunction and axonal degeneration.

PMID- 16647882
TI  - Integration bias of gammaretrovirus vectors following transduction and growth of
      primary mouse hematopoietic progenitor cells with and without selection.
AB  - The recent recognition that recombinant retrovirus vectors can induce oncogenic
      transformation has stimulated much interest in the pattern of vector integration
      sites. We report here on the integration pattern of a gammaretrovirus reporter
      vector following transduction and ex vivo culture of primary mouse bone marrow
      progenitor cells in the absence and presence of drug selection. Using a novel
      method of cloning junction fragments, we observed no bias for integrations within
      genes, but did observe a bias for integrations within gene-dense regions and
      especially near transcriptional start sites of highly active genes, similar to
      previous reports in other cell types. We also document a novel bias for
      integrations within or near a class of genes that encode nuclear-localized
      proteins. We found that drug selection resulted in an increase in the frequency
      of recovered integration events that were located within the beginning of genes,
      integration events that were located in less gene-dense regions, and integration
      events that were oriented in an antisense direction relative to flanking gene
      transcription. Taken together, these studies provide new insights into the nature
      of retrovirus vector integration patterns in primary cells and demonstrate that
      selection based on vector expression can bias the integration site repertoire.

PMID- 16647883
TI  - HIV integration site selection: targeting in macrophages and the effects of
      different routes of viral entry.
AB  - We have studied the selection of HIV DNA integration sites in primary macrophages
      to investigate two questions. First, mature macrophages do not divide, allowing
      us to investigate whether HIV integration targeting differs between dividing
      cells and nondividing cells. We sequenced and analyzed 754 unique integration
      sites and found that integration in macrophages is favored in active
      transcription units (TUs), as was observed previously for other cell types.
      However, HIV integration in genes was slightly less favored in macrophages than
      in dividing PBMC or T cell lines. Second, we compared integration targeting by
      HIV-vector particles bearing either of two different envelope proteins (HIV R5
      Env or VSV-G) to determine whether the mechanism of entry influenced subsequent
      integration targeting. Integration sites generated by HIV R5- or VSV-G-bearing
      particles showed no significant differences in their distributions in the human
      genome. Analysis of additional published integration site sequences also
      indicated that the route of entry did not affect integration site selection for
      other viral envelopes as well.

PMID- 16647884
TI  - Long-term effects of tiagabine monotherapy on cognition and mood in adult
      patients with chronic partial epilepsy.
AB  - The long-term effects of tiagabine monotherapy on cognition and mood were
      evaluated in adult patients with chronic partial epilepsy in a 48-week, open
      label extension period that followed an 8-week, double-blind, titration study.
      Cognitive function was evaluated using neuropsychological evaluations that
      measured learning and memory, general intellectual ability, attention and mental
      speed, and reaction speed. Mood was assessed using a Finnish modification of the
      Profile of Mood States. Of the 34 patients who entered the open-label extension
      period, 18 successfully continued long-term monotherapy and underwent
      neuropsychological evaluation at 48 weeks of tiagabine monotherapy. The mean
      daily dose of tiagabine monotherapy at the end of open-label treatment was 19.7
      mg/day (range, 5-35 mg/day). Tiagabine monotherapy did not adversely affect
      cognitive function. No significant changes in mood were observed. The median
      number of seizures was 2 (range, 0-71), and 8 patients (44%) were seizure-free
      during the 48 weeks of open-label tiagabine treatment. The results of this small
      open-label extension study indicate that patients with chronic partial epilepsy
      who were successfully converted to long-term tiagabine monotherapy demonstrated
      no adverse effects on cognitive function or mood.

PMID- 16647885
TI  - Prediction of arrhythmic events with positron emission tomography: PAREPET study
      design and methods.
AB  - BACKGROUND: In medically-treated patients with ischemic cardiomyopathy,
      myocardial viability is associated with a worse prognosis than scar. The risk is
      especially great with hibernating myocardium (chronic regional dysfunction with
      reduced resting flow), and the excess mortality appears to be due to sudden
      cardiac death (SCD). Hibernating myocardium also results in sympathetic nerve
      dysfunction, which has been independently associated with risk of SCD.
      OBJECTIVES: PAREPET is a prospective, observational cohort study funded by NHLBI.
      It is designed to determine whether hibernating myocardium and/or inhomogeneity
      of sympathetic innervation by positron emission tomography imaging identifies
      patients with ischemic cardiomyopathy who are at high risk for SCD and
      cardiovascular mortality. METHODS: Patients with documented ischemic
      cardiomyopathy, an ejection fraction of <or=35%, and with no plans for coronary
      revascularization will be recruited. Major exclusion criteria include: history of
      resuscitated SCD, sustained VT, ICD discharge, or unexplained syncope; recent
      myocardial infarction (30 days), percutaneous coronary intervention (3 months),
      coronary bypass surgery (1 year); or comorbidities that would be expected to
      reduce life expectancy to <2 years. All patients will undergo transthoracic
      echocardiography, and dynamic cardiac positron emission tomography to quantify
      resting perfusion (13N-ammonia), norepinephrine uptake as an index of sympathetic
      innervation (11C-meta-hydroxyephedrine), and metabolic viability (18F-2
      deoxyglucose during glucose-insulin clamp). The development of SCD or
      cardiovascular mortality will be determined by telephone follow-up every three
      months. In patients with an implantable cardiac defibrillator, appropriate device
      discharge will be considered a surrogate for SCD. CONCLUSION: The PAREPET study
      will prospectively determine whether the amount of viable dysfunction myocardium
      and/or cardiac sympathetic dysinnervation is associated with the risk of SCD. It
      is anticipated that the results of this trial will more specifically identify
      myocardial substrates of SCD. This will help target therapies intended to reduce
      arrhythmic death to those patients with the greatest likelihood of benefit.

PMID- 16647887
TI  - Are women who are treated for hypothyroidism at risk for pregnancy complications?
AB  - OBJECTIVE: The purpose of this study was to investigate the outcomes that are
      associated with pregnancy and treated hypothyroidism. STUDY DESIGN: This was a
      retrospective cohort study of all women who received prenatal care and were
      delivered at the University of California, San Francisco, between 1989 and 2001.
      All patients with hypothyroidism diagnosed before pregnancy or early in pregnancy
      were identified. Maternal, fetal, and obstetric outcomes were then collected and
      analyzed for women with hypothyroidism and compared with women without
      hypothyroidism. RESULTS: Among 20,499 deliveries, there were 419 women (2.1%) who
      were treated for hypothyroidism during the study period. Hypothyroidism was more
      common among women > or =35 years old, white women, and women without Medicaid
      insurance. Treated hypothyroidism was not associated with any increase in
      maternal, fetal, or neonatal complications. In addition, hypothyroidism did not
      affect mode of delivery. CONCLUSION: Compared with patients without
      hypothyroidism, patients with treated hypothyroidism are not at any increased
      risk for perinatal morbidity.

PMID- 16647886
TI  - Parathyroid hormone stimulates expression of the Notch ligand Jagged1 in
      osteoblastic cells.
AB  - We previously demonstrated that activation of the Parathyroid Hormone Receptor
      (PTH1R) in osteoblastic cells increases the Notch ligand Jagged1 and expands
      hematopoietic stem cells (HSC) through Notch signaling. However, regulation of
      Jagged1 by PTH in osteoblasts is poorly understood. The present study
      demonstrates that PTH treatment increases Jagged1 levels in a subpopulation of
      osteoblastic cells in vivo and in UMR106 osteoblastic cells in vitro. Since PTH(1
      34) activates both Adenylate Cyclase/Protein Kinase A (AC/PKA) and Protein Kinase
      C (PKC) downstream of the PTH1R in osteoblastic cells, we independently
      determined the effect of either pathway on Jagged1. Activation of AC with
      Forskolin or PKA with PTH(1-31) or cell-permeable cAMP analogues increased
      osteoblastic Jagged1. This PTH-dependent Jagged1 increase was blocked by H89 and
      PKI, specific PKA inhibitors. In contrast, PKC activation with phorbol ester
      (PMA) or PTH(13-34) did not stimulate Jagged1 expression, and PTH-dependent
      Jagged1 stimulation was not blocked by Go6976, a conventional PKC inhibitor.
      Therefore, PTH treatment stimulates osteoblastic Jagged1 mainly through the
      AC/PKA signaling pathway downstream of the PTH1R. Since Jagged1/Notch signaling
      has been implicated not only in stromal-HSC interactions but also in osteoblastic
      differentiation, Jagged1 may play a critical role in mediating the PTH-dependent
      expansion of HSC, as well as the anabolic effect of PTH in bone.

PMID- 16647888
TI  - Face presentation: predictors and delivery route.
AB  - OBJECTIVE: We sought to identify associated characteristics of face presentation
      and to examine factors that were associated with mode of delivery in the setting
      of face presentation. STUDY DESIGN: This was a retrospective cohort study of
      women who were diagnosed with face presentation during labor. We examined
      maternal, fetal, and labor characteristics to determine the associations and
      predictors of cesarean delivery. RESULTS: Fetuses in face presentation were more
      likely preterm, < 2500 g, and black. An Apgar score of < 7 at 5 minutes was more
      common in face presentation (10.9%) compared with vertex presentation (4.4%; P =
      .018). Rates of umbilical artery base excess < -12 or pH < 7.0 were not
      different. Cesarean delivery was less common in women who received oxytocin
      (adjusted odds ratio, 0.18; 95% CI, 0.03-0.95) and in women with mentum anterior
      (14%) as compared with mentum posterior presentation (85%; P < .001). CONCLUSION:
      This study confirms the association between face presentation and prematurity.
      The association with black ethnicity may be related to differences in pelvic
      anatomy. Although face presentation was associated with decreased Apgar scores,
      no other indicators of fetal asphyxia were identified. Cesarean delivery rates
      were higher in women with mentum posterior face presentation and in women who did
      not receive oxytocin.

PMID- 16647889
TI  - Utility of Acute Physiology, Age, and Chronic Health Evaluation (APACHE III)
      score in maternal admissions to the intensive care unit.
AB  - OBJECTIVE: A mean Acute Physiology, Age, and Chronic Health Evaluation (APACHE
      III) score of > 50 is associated with increased intensive care unit mortality
      rate in nonpregnant cardiac and trauma patients. The objective was to determine
      the usefulness of the APACHE III score in maternal admissions to an intensive
      care unit in a tertiary care center in an urban multicultural city. STUDY DESIGN:
      This was a retrospective review of all maternal admissions (> 20 weeks of
      gestation or after delivery) to an intensive care unit between January 2002 and
      May 2004. Demographics, obstetric and medical history, and 20 physiologic
      variables that comprise the APACHE III were recorded. The minimum APACHE III
      score (lowest risk of death) is 0; maximum is 299. The association between APACHE
      III score and maternal death was assessed with Mann Whitney U test. Significance
      was assumed at a probability value of < .05. RESULTS: Fifty-eight subjects met
      the study criteria. Thirty percent of these women were admitted antepartum (27 +/
      1.0 weeks of gestation); 31% of the women were admitted on the day of delivery;
      and 29% of the women were admitted after delivery. Mean maternal age was 27 +/-
      6.7 years. Acute conditions that resulted in transfer to the intensive care unit
      included preeclampsia (24%), cardiorespiratory disease (21%), hemorrhage (16%),
      infection (12%), trauma (7%), and thromboembolism (3%). Fifty-five percent of the
      women had no previous underlying obstetric complications, and 98% of the women
      had no underlying chronic health condition. Fifty-eight percent of the women
      received care in a medical intensive care unit; 28% of the women received care in
      a surgical intensive care unit; 10% of the women received care in a cardiac
      intensive care unit, and 3% of the women received care in a neurologic intensive
      care unit. The mean intensive care unit stay was 3.7 +/- 4.6 days, and the mean
      hospital stay was 9.0 +/- 7 days. Three patients died; the rest of the patients
      went home in good condition. The median APACHE III score was 34 (range, 14-102)
      and was not correlated with maternal death. CONCLUSION: The APACHE III is not
      associated with risk of intensive care unit-related maternal death.

PMID- 16647890
TI  - Women with one elevated 3-hour glucose tolerance test value: are they at risk for
      adverse perinatal outcomes?
AB  - OBJECTIVE: The purpose of this study was to examine whether women with one
      elevated value of the 3-hour glucose tolerance test are at increased risk for
      adverse perinatal outcomes. STUDY DESIGN: This was a retrospective cohort study
      of singleton pregnancies that were screened for gestational diabetes mellitus
      with the use of the glucose loading test and with a glucose tolerance test for
      follow up, if screened values were positive. Perinatal outcomes in women with one
      elevated glucose tolerance test value were compared with the outcomes in women
      who screened negative by glucose loading test. The chi-square test was used to
      compare categorical outcomes, and multivariate logistic regression analysis was
      used to control for potential confounding factors; a P value of < .05 indicated
      statistical significance. RESULTS: Of 14,036 women who met the study criteria,
      women with one elevated glucose tolerance test value exhibited higher rates of
      cesarean delivery (in nulliparous women only), preeclampsia, chorioamnionitis,
      birth weight > 4000 g and > 4500 g, and neonatal admission to the intensive care
      nursery as compared with women who screened negative (P < .05 for all).
      CONCLUSION: Although women with one elevated glucose tolerance test value are not
      diagnosed with gestational diabetes mellitus, they are still at risk for adverse
      perinatal outcomes.

PMID- 16647891
TI  - Retrospective cohort study of surgical staging for ovarian low malignant
      potential tumors.
AB  - OBJECTIVE: The purpose of this study was to determine the benefit of surgically
      staging ovarian low malignant potential tumors. STUDY DESIGN: This was a
      retrospective cohort study of all ovarian low malignant potential tumors that
      were diagnosed by frozen section or final pathologic review from 2003 to 2005.
      RESULTS: Twenty-two of 32 patients (69%) were staged surgically. Sixteen low
      malignant potential tumors were stage I by final pathologic review, and 4 tumors
      were upstaged to stage II-III disease. Two other patients had early invasive
      ovarian carcinoma, despite a frozen section that suggested low malignant
      potential; 1 patient received adjuvant chemotherapy. The tumors of 10 women (31%)
      were unstaged. Frozen section suspicion of low malignant potential (P = .003) and
      surgery by a gynecologic oncologist (P < .001) correlated with staging.
      Preoperative CA-125, intraoperative blood loss, and postoperative hospitalization
      were increased in patients with staged disease (each P < .05). Two women who
      underwent fertility-sparing surgery experienced a recurrence in the contralateral
      ovary. CONCLUSION: Surgical staging of ovarian low malignant potential tumors has
      limited value for most patients, unless invasive carcinoma is diagnosed by final
      pathologic review.

PMID- 16647892
TI  - Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin:
      study in human gynecologic cancer cell lines and in rodent heart.
AB  - OBJECTIVE: The purpose of this study was to investigate whether resveratrol adds
      to the growth inhibitory effects of cisplatin and doxorubicin on ovarian and
      uterine cancer cells and to evaluate whether resveratrol diminishes the cardiac
      toxicity of doxorubicin in rodent heart. STUDY DESIGN: Human ovarian (OVCAR-3)
      and uterine (Ishikawa) cancer cells in culture were treated with cisplatin and
      doxorubicin, respectively, with and without resveratrol; and cell growth and
      viability were evaluated. Neonatal rat ventricular myocytes received doxorubicin
      in the presence and absence of resveratrol, and cell viability was evaluated.
      Mice received doxorubicin +/- resveratrol, and electrocardiograms were evaluated.
      Data were analyzed with analysis of variance and Scheffe's test. RESULTS:
      Resveratrol combined with cisplatin or with doxorubicin demonstrated an additive
      growth-inhibitory anticancer effect with a left shift of the cisplatin and
      doxorubicin dose/response curves. Resveratrol increased the viability of neonatal
      rat ventricular myocytes that were treated with doxorubicin and reduced
      doxorubicin-induced bradycardia and QTc interval prolongation in mice.
      CONCLUSION: Resveratrol adds to the growth inhibitory/anticancer activity of
      cisplatin and doxorubicin in vitro and protects against doxorubicin-induced
      cardiac toxicity both in vitro and in mice.

PMID- 16647893
TI  - Loss of communication in ovarian cancer.
AB  - OBJECTIVE: This study was undertaken to investigate the expression of connexins
      in ovarian cancer cell lines and assess correlation with chemosensitivity. STUDY
      DESIGN: Eight cell lines were used in this study. Cytotoxicity assays with
      carboplatin and paclitaxel were performed. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to analyze the expression of gap junction proteins.
      Western blotting and immunohistochemical staining of selective gap junction
      proteins (connexin 26 and 43) were performed. RESULTS: All 11 connexins were
      detected with RT-PCR profiling in ovarian cancer cells. Further experiments were
      performed to analyze protein expression with connexins 26 and 43. Levels of
      connexin proteins did not correlate with gene expression obtained with RT-PCR.
      Results obtained with immunoblotting were confirmed by immunohistochemistry.
      Carboplatin and paclitaxel sensitivities were determined and connexin 43
      expression was associated with sensitivity to paclitaxel. CONCLUSION: Expression
      of connexins is regulated at the translational level in ovarian cancer.
      Sensitivity to paclitaxel maybe associated with connexin 43.

PMID- 16647894
TI  - Trends in weight gain during pregnancy: a population study across 16 years in
      North Carolina.
AB  - OBJECTIVE: This study was undertaken to examine the proportion of women meeting
      established weight gain recommendations during pregnancy. STUDY DESIGN:
      Retrospective cohort using chi2 and logistic regression analysis of 1,463,936
      registered North Carolina births from 1988 to 2003. RESULTS: The percentage of
      pregnant women achieving recommended weight gain decreased significantly (down
      6.3%) between 1988 and 2003. CONCLUSION: Despite Institute of Medicine guidelines
      and a Healthy People 2010 goal aimed at improving the health of women and infants
      by optimizing weight gain during pregnancy, the proportion of women in North
      Carolina with inappropriately low or excessive weight gain increased. We need to
      reexamine interventions designed to support appropriate weight gain during
      pregnancy.

PMID- 16647895
TI  - Effects of menstrual cycle and oral contraceptive use on serum levels of lipid
      soluble antioxidants.
AB  - OBJECTIVE: The purpose of this study was to examine the influence of menstrual
      cycle and oral contraceptive use on serum levels of lipid-soluble antioxidants.
      STUDY DESIGN: In this cross-section study, nonfasting blood samples were
      collected twice from 10 healthy premenopausal women during the follicular phase
      (between days 8 and 11) and the luteal phase (between days 18 and 22) of their
      same menstrual cycle. In addition, blood samples from 15 premenopausal women who
      used oral contraceptive for at least 6 months and 40 women who did not use oral
      contraceptive were collected randomly at any day of the menstrual cycle. Serum
      levels of coenzyme Q10, alpha-tocopherol, gamma-tocopherol, beta-carotene, alpha
      carotene, and lycopene were determined using high pressure liquid chromatography.
      RESULTS: Serum coenzyme Q10 and alpha-tocopherol levels were significantly lower
      during the follicular phase compared with the luteal phase of the same menstrual
      cycle (P < .05). Oral contraceptive use also significantly decreased coenzyme Q10
      and alpha-tocopherol (P < .001). Other antioxidant levels were comparable.
      CONCLUSION: Alterations in coenzyme Q10 and alpha-tocopherol levels during the
      menstrual cycle and in oral contraceptive users should be taken into
      consideration, concerning the future antioxidant research in premenopausal women.
      Further studies are needed to investigate the potential role of endogenous and
      exogenous ovarian hormones on oxidative stress in women.

PMID- 16647896
TI  - Significance of accidental extensions in the lower uterine segment during
      cesarean delivery.
AB  - OBJECTIVES: This study was undertaken to determine risk factors and perioperative
      complications associated with accidental extensions in the lower uterine segment
      during cesarean deliveries (CDs). STUDY DESIGN: This is a retrospective chart
      review of all CDs performed at Jackson Memorial Hospital/University of Miami
      between the years 1999 and 2002. Operative reports were reviewed to abstract data
      on the occurrence of extensions. Indication for CD, cervical status at the time
      of CD, birth weight, and fetal presentation and position were included in the
      analyses. Postoperative hematocrits, length of surgery, estimated blood loss,
      decline in hematocrit by 10%, need for transfusion, or hysterectomy were compared
      among CD with and without extensions. RESULTS: A total of 2,811 CDs were
      available for this study. Accidental extensions in the lower uterine segment
      occurred in 6.6% of the cases. Extensions were more commonly found in primary CD
      (8% vs 5%, P < .01. Extensions were more frequent if cervical dilatation was 8 cm
      or greater (18.3% vs 7%, P < .01), complete effacement (15% vs 8%, P < .01)
      station greater than +1 (16% vs 6.9%, P < .01), and if the fetal position was
      noted to be in the occiput posterior position (10% vs 5%, P < .01). When
      extensions were present, length of surgery was longer (56 vs 49 minutes, P < .01)
      and estimated blood loss was greater (994 +/- 675 mL vs 936 +/- 370 mL, P < .01).
      Arrest of descent as indication for CD was found to be an independent risk factor
      for the occurrence of extensions during CD (odds ratio 2.6, 95% CI 1.5-4.5, P =
      .001). CONCLUSION: Extensions in the lower uterine segment during CD do not
      increase maternal morbidity.

PMID- 16647897
TI  - Characteristics of patients with abnormal glucose challenge test and normal oral
      glucose tolerance test results: comparison with normal and gestational diabetic
      patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the characteristics and
      outcomes of patients who had abnormal glucose challenge test results and
      subsequent normal oral glucose tolerance test results and to assess whether such
      patients are at a greater risk than normal pregnant patients for adverse
      perinatal outcome. STUDY DESIGN: In this retrospective cohort study that was
      conducted between June and December 2003, 101 pregnant women (group A) had an
      abnormal glucose challenge test result and a normal oral glucose tolerance test
      result. Data were also collected on 2 control groups: 100 pregnant women with
      normal glucose challenge test results (group B) and all 76 pregnant women who
      were diagnosed with gestational diabetes mellitus during this period of time
      (group C). Patients with multiple pregnancies, chronic hypertension,
      pregestational diabetes mellitus, or any other maternal or fetal problems that
      were diagnosed before 24 weeks (when the glucose challenge test was performed)
      were excluded from the study groups. The following data were collected and
      analyzed: maternal age, maternal weight and height, parity and gravidity,
      diabetes mellitus in first-degree relatives, medical and obstetric history,
      ethnicity, complications during the third trimester of pregnancy, birth weight,
      gestational age at delivery, mode of delivery, Apgar scores, cord blood gas
      results, maternal complications of labor and during the postpartum period, and
      infant admission to the neonatal intensive care unit. For comparison between
      groups, we used the Student t test, 1-way analysis of variance, the chi-square
      test, and stepwise logistic regression. RESULTS: Patients in groups A and C were
      significantly older compared with group B (29.2 +/- 5.6 years and 30.4 +/- 5.5
      years, respectively, vs 24.8 +/- 5.5 years; P < .01), had a lesser rate of
      primiparity (48% and 31%, respectively, vs 24%; P < .05), had greater body mass
      index (30.8 +/- 5 kg/m2 and 31.3 +/- 6 kg/m2, respectively, vs 29.2 +/- 4.4
      kg/m2; P < .01), had a greater rate of previous gestational diabetes mellitus (6%
      and 20%, respectively, vs 0%; P < .05), and had a greater rate of first-degree
      family members with diabetes mellitus (21% and 21%, respectively, vs 3%; P <
      .01). None of the outcome parameters was statistically significant when group A
      was compared with group B. CONCLUSION: Patients with an abnormal glucose
      challenge test result and a subsequent normal oral glucose tolerance test result
      have different maternal characteristics and backgrounds compared with patients in
      whom both test results are normal, yet both groups have normal outcomes. We
      should continue to consider patients who have an abnormal glucose challenge test
      result and subsequent normal oral glucose tolerance test result as low-risk;
      however, these findings may represent an indication of an increased likelihood
      for the development of overt diabetes mellitus later in life.

PMID- 16647898
TI  - Glucose challenge test threshold values in screening for gestational diabetes
      among black women.
AB  - OBJECTIVE: The objective of the study was to assess the incidence of gestational
      diabetes among black women according to various cut-off values of the glucose
      challenge test. STUDY DESIGN: We performed a retrospective chart review of black
      patients who had a 50-g, 1-hour glucose challenge test between 24 and 28 weeks'
      gestation of 130 mg/dL or higher followed by a 100-g, 3-hour glucose tolerance
      test. Results were categorized in 10-mg/dL increments. Gestational diabetes was
      diagnosed by 2 or more abnormal values using the Carpenter-Coustan criteria.
      RESULTS: The study included 387 patients. The incidence of gestational diabetes
      diagnosed overall in all patients with a glucose challenge test of 130 mg/dL or
      higher was 31.2%. The incidence of gestational diabetes in individuals with a
      challenge test in the range of 130 to 140 mg/dL was 10.7%. The incidence of
      gestational diabetes with a screening test of 180 mg/dL or higher was 72.0%.
      CONCLUSION: Our data support the use of 130 mg/dL as the threshold for a positive
      glucose challenge test and suggest the use of a glucose tolerance test to confirm
      the diagnosis of gestational diabetes for screening values up to 200 mg/dL.

PMID- 16647899
TI  - Manual rotation of the fetal occiput: predictors of success and delivery.
AB  - OBJECTIVE: The purpose of the study was to define predictors of successful
      rotation and rate of cesarean delivery after manual rotation of the fetal occiput
      from occiput posterior or transverse position. STUDY DESIGN: A retrospective
      cohort study comprised patients who underwent a trial of manual rotation of the
      fetal occiput from occiput posterior or occiput transverse position. Successful
      rotation was defined as delivery in the occiput anterior position. We examined
      maternal, fetal, and labor characteristics as predictors of both fetal position
      at delivery and cesarean delivery. RESULTS: Multiparity (odds ratio, 2.5; 95% CI,
      1.5-3.8) and maternal age < 35 years (odds ratio, 2.0; 95% CI, 1.1-3.4) were
      associated with successful manual rotation of the fetal occiput. After successful
      rotation, the cesarean delivery rate was 2%, compared with 34% if the rotation
      failed (P < .001). Asian ethnicity, nulliparity, age > 35 years, labor induction,
      and epidural usage were associated with higher rates of cesarean delivery.
      CONCLUSION: After successful manual rotation of the fetal occiput, women had
      lower cesarean delivery rates than women with unsuccessful rotations. Multiparity
      and maternal age of < 35 years were associated with more successful rotations.

PMID- 16647901
TI  - Understanding the effects of SERMs on cardiovascular disease.

PMID- 16647902
TI  - Unexpected results of an important trial of vitamins C and E administration to
      prevent preeclampsia.

PMID- 16647903
TI  - Incidence, origin, and character of cerebral injury in twin-to-twin transfusion
      syndrome treated with fetoscopic laser surgery.
AB  - OBJECTIVE: The objective of the study was to determine the incidence, origin, and
      character of cerebral lesions in monochorionic twins with twin-to-twin
      transfusion syndrome treated with fetoscopic laser surgery. STUDY DESIGN: This
      was a prospective study of monochorionic twins with twin-to-twin transfusion
      syndrome treated with fetoscopic laser surgery and monochorionic twins without
      twin-to-twin transfusion syndrome delivered at our center between June 2002 and
      September 2005, using cranial ultrasonography. RESULTS: Incidence of antenatally
      acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group
      was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group
      (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in
      the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to
      twin transfusion syndrome group (P = .04). Antenatal injury was responsible for
      severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome
      group. CONCLUSION: Incidence of severe cerebral lesions in twin-to-twin
      transfusion syndrome treated with fetoscopic laser surgery is high and results
      mainly from antenatal injury.

PMID- 16647904
TI  - Preventive ethics for including women of childbearing potential in clinical
      trials.
AB  - OBJECTIVE: We present a preventive ethics approach for including women of
      childbearing potential in clinical trials. STUDY DESIGN: We explain the concept
      of preventive ethics and identify its implications for study design, the informed
      consent process, and study management. RESULTS: We identify and address ethically
      significant questions for investigators and institutional review boards to
      address, to responsibly enroll women of childbearing potential in clinical
      trials. These questions concern preventive ethics for study design, for the
      informed consent process, and for study management. Distinctive components of
      this preventive ethics approach include the distinction between directive and
      nondirective counseling, the recognition of the concept of moral risk for women
      as research subjects, and the distinction between professional and individual
      conscience. We identify ethical considerations for physicians considering
      referral of their patients to clinical trials. CONCLUSION: A comprehensive,
      preventive ethics approach to the ethical challenges in clinical trials related
      to the prevention and occurrence of pregnancy is essential for responsibly
      enrolling women of childbearing potential.

PMID- 16647905
TI  - Progesterone for the prevention of preterm birth among women at increased risk: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: This study was undertaken to determine whether progestational agents,
      initiated in the second trimester of pregnancy, reduce the risk of delivery less
      than 37 weeks, among women at increased risk of spontaneous preterm birth. STUDY
      DESIGN: Medline, pre-Medline, EMBASE, and Cochrane Central Register of Controlled
      Trials were searched. Randomized controlled trials with less than 20% lost to
      follow-up were included. RESULTS: Three trials were eligible for inclusion. There
      was a significant reduction in risk of delivery less than 37 weeks with
      progestational agents (relative risk [95% CI] = 0.57 [0.36-0.90]). There was no
      significant effect on perinatal mortality or serious neonatal morbidity.
      CONCLUSION: Progestational agents, initiated in the second trimester of
      pregnancy, may reduce the risk of delivery less than 37 weeks' gestation, among
      women at increased risk of spontaneous preterm birth, but the effect on neonatal
      outcome is uncertain. Larger randomized controlled trials are required to
      determine whether this treatment reduces perinatal mortality or serious neonatal
      morbidity.

PMID- 16647906
TI  - External anal sphincter volume measurements using 3-dimensional endoanal
      ultrasound.
AB  - OBJECTIVE: Significant nerve injury to a muscle can be associated with muscle
      atrophy and volume loss. Three-dimensional (3D) ultrasound can measure muscle
      volume, but the reproducibility of the technique has not been established for the
      anal sphincter. STUDY DESIGN: Using a 10 MHz 360-degree rotating endoanal probe,
      we performed 3D endoanal ultrasounds on 9 nulliparous and 23 asymptomatic
      primiparous subjects at 12 weeks' postpartum. Two blinded examiners measured the
      length of the external anal sphincter (EAS) from a midsagittal image, and the
      width of the EAS and internal anal sphincter (IAS) from axial images at mid anal
      canal. The EAS volume was calculated by repetitively outlining only the EAS in
      each sequential axial view. Both examiners measured the EAS volumes twice,
      blinded to previous calculations. RESULTS: The intrarater reliability for EAS
      volume was 0.79 to 0.89 (intraclass coefficient). The mean difference of the EAS
      volume between the 2 examiners was 0.5 mL (P = .3, t test). Correlation between
      the 2 examiners for measuring EAS volume was r = 0.77 (P < .001, Pearson's). The
      "limits of agreement" (between 2 examiners) varied by as much as 40% of the mean
      volume. CONCLUSION: Quantitative 3D ultrasound of the anal sphincter is
      moderately reproducible.

PMID- 16647907
TI  - The effect of raloxifene on cardiac autonomic regulation in osteoporotic women.
AB  - OBJECTIVE: There are suggestive data that raloxifene may have favorable effects
      on the arterial systems in postmenopausal women and thereby lowering the
      incidence of future adverse cardiovascular events. Reduction of heart rate
      variability appears to be a marker for identifying subjects with an increased
      risk for cardiac mortality, particularly in patients after myocardial infarction
      and in elderly people. Although there are conflicting data with regard to the
      effects of estrogen and progesterone on heart rate variability in postmenopausal
      women, the impact of raloxifene treatment on heart rate variability is fully
      unknown. STUDY DESIGN: Forty-three osteoporotic postmenopausal women were
      recruited in a prospective, randomized, and placebo-controlled 6-month study. Of
      these women, 23 received raloxifene hydrocloride, 60 mg once daily, whereas 20
      women received alendronate, 10 mg daily. Time and frequency domains of heart rate
      variability were measured at baseline and at 3 months and 6 months of the
      treatment. RESULTS: Time domain indices of heart rate variability, mean RR, and
      SD of all beat-to-beat intervals remained identical within the groups at the end
      of treatment. The square root of the mean of the sum of squares of successive RR
      intervals, a sensitive index of parasympathetic activity, tended to increase with
      raloxifene. Frequency domain indices of heart rate variability were as follows:
      low-frequency power of heart rate variability tended to stay the same, compared
      with the baseline values in both treatment regimens. High-frequency power of
      heart rate variability increased significantly in the raloxifene group (P = .039)
      at 3 months, and this significance persisted at the end of the treatment. A
      nonsignificant decrease was observed in the alendronate group. Accordingly, the
      low-frequency power/high-frequency power ratio, an index of sympathovagal
      balance, decreased significantly by the raloxifene treatment (P = .028) at 3
      months and persisted at 6 months. There was no significant change in low
      frequency power/high-frequency power ratio of patients taking alendronate.
      CONCLUSION: Raloxifene seems to have a positive effect on cardiac autonomic
      regulation in postmenopausal osteoporotic women. This observation could at least
      partially explain the reduced cardiovascular events in the subset of women with
      increased cardiovascular risk in the Multiple Outcomes of Raloxifene Evaluation
      trial. However, the results of ongoing studies should be awaited to have a
      conclusion of its effects on the cardiovascular system.

PMID- 16647908
TI  - Women's health 18 years after rupture of the anal sphincter during childbirth: I.
      Fecal incontinence.
AB  - OBJECTIVE: We studied the long-term outcome after an anal sphincter tear. STUDY
      DESIGN: From a cohort of 4569 women who gave birth in 1982 to 1983, we identified
      445 (9.7%) who sustained a sphincter tear and 445 controls. Eighteen years after
      the delivery, we mailed them a questionnaire and graded fecal incontinence with
      the Wexner score, a summary of incontinence to flatus, liquid, or solid stools;
      need to wear a pad; and lifestyle alterations. We predefined severe incontinence
      as a score above 4 of 20. RESULTS: Five hundred forty of 890 women (61%) returned
      the questionnaire. Severe fecal incontinence was reported by 34 of 259 women
      (13.1%) after a sphincter tear and 22 of 281 controls (7.8%) (risk ratio 1.7, 95%
      confidence interval 1.0 to 2.8). Only 6.4% of the reports of fecal incontinence
      were attributable to a sphincter tear. CONCLUSION: Fecal incontinence is
      frequently reported, even by women who have not sustained an anal sphincter tear.
      Only a small fraction of fecal incontinence can be attributed to sphincter tears.

PMID- 16647909
TI  - Lipids in polycystic ovary syndrome: role of hyperinsulinemia and effects of
      metformin.
AB  - OBJECTIVE: Patients with polycystic ovary syndrome frequently suffer from
      hyperinsulinemia and adverse lipid profile. This study evaluated effects of
      metformin on lipid profile. STUDY DESIGN: Lipid profiles in hyperinsulinemic (n =
      43) and normoinsulinemic (n = 45) subjects were compared. Hyperinsulinemic
      subjects were treated with metformin (500 mg po tid) and lipid profiles were
      reevaluated at 3 and 6 months of treatment. RESULTS: The hyperinsulinemic group
      had significantly lower high-density lipoprotein (HDL) (by 11%), higher total
      cholesterol to HDL ratio (by 23%), and greater triglycerides (by 57%) than the
      normoinsulinemic group. Six-month metformin therapy in hyperinsulinemic women was
      associated with a significant decrease of insulin level (by 35%), total
      cholesterol (by 11%), low-density lipoprotein (LDL) (by 12%), and triglycerides
      (by 33%). Levels of lipids in hyperinsulinemic women after metformin therapy were
      comparable to levels observed in normoinsulinemic subjects. CONCLUSION: The
      present study supports the notion that metformin may be considered as a
      prophylactic therapy lowering cardiovascular risk factors in hyperinsulinemic
      women with polycystic ovary syndrome.

PMID- 16647910
TI  - The effects of intravaginal clindamycin and metronidazole therapy on vaginal
      lactobacilli in patients with bacterial vaginosis.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of 3
      intravaginal antibacterial treatments on vaginal lactobacilli in patients with
      bacterial vaginosis (BV). STUDY DESIGN: Retrospective analyses were performed on
      Lactobacillus scores from 3 similar studies evaluating 2 2% clindamycin vaginal
      creams and 0.75% metronidazole gel at baseline and at 21 to 30 days in 408
      patients with BV. Scores were compared using a 1-way global F test and McNemar's
      test. RESULTS: All groups had similar mean Lactobacillus scores at baseline (P =
      0.37) and at 21 to 30 days (P = .71). The 3 groups were also comparable at both
      visits with respect to the distributions of scores within each group. In all
      groups, there was significant improvement in the percentages of patients with no
      lactobacilli present at 21 to 30 days compared with baseline (P < .0001 for all
      comparisons). CONCLUSION: Clindamycin and metronidazole promoted similar levels
      of restoration of vaginal lactobacilli at 21 to 30 days.

PMID- 16647911
TI  - Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent
      recurrent bacterial vaginosis.
AB  - OBJECTIVE: Efficacy study of suppressive vaginal metronidazole in reducing
      recurrent symptomatic episodes of bacterial vaginosis. STUDY DESIGN: Multicenter
      prospective study with initial 10-day open-label metronidazole gel in which
      asymptomatic responders randomly assigned to receive twice weekly metronidazole
      vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. RESULTS: Of 157
      eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable
      women (88.2%) responded clinically and were randomly assigned. During suppressive
      therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving
      metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR]
      0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence
      occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68,
      CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for
      metronidazole compared with 39% on placebo, which declined to 34% and 18%,
      respectively, by 28 weeks follow-up. Adverse effects were uncommon; however,
      secondary vaginal candidiasis occurred significantly more often in metronidazole
      treated women (P = .02). CONCLUSION: Suppressive therapy with twice-weekly
      metronidazole gel achieves a significant reduction in the recurrence rate of
      bacterial vaginosis; however, secondary vaginal candidiasis is common.

PMID- 16647912
TI  - Contraceptive use and discontinuation: findings from the contraceptive history,
      initiation, and choice study.
AB  - OBJECTIVE: The purpose of this study is to provide insight on the continuing high
      rate of unintended pregnancy among adult women. STUDY DESIGN: Contracepting women
      were recruited while they waited for primary care appointments. A total of 369
      completed the baseline questionnaire, and 145 oral contraceptive (OC) users were
      enrolled in a 5-week, diary-based study of adherence and sexual activity.
      RESULTS: Most women who reported having discontinued OCs did so because of
      medical side effects, and most had switched to less effective methods. Among OC
      users, 26.4% had sexual intercourse on days they missed pills just before or
      after their placebo week. Nonadherence did not differ by socioeconomic factors or
      obesity. CONCLUSION: Clinicians may need to encourage their patients to discuss
      their reasons for wanting to discontinue the use of an effective contraceptive
      method and assist them with their concerns or to switch to other effective
      methods to protect themselves from unintended pregnancy.

PMID- 16647913
TI  - Overexpression of kallikrein 10 (hK10) in uterine serous papillary carcinomas.
AB  - OBJECTIVE: Kallikrein 10 is a secreted serine protease recently implicated in the
      growth and invasion of several human tumors. The goal of this study was to
      investigate the expression and secretion levels in vitro and in vivo of
      kallikrein 10 in uterine serous papillary carcinoma, a highly aggressive variant
      of endometrial tumor. STUDY DESIGN: Human kallikrein 10 gene expression levels
      were evaluated in 11 snap-frozen uterine serous papillary carcinoma biopsies and
      6 normal endometrial cell biopsies by real-time polymerase chain reaction.
      Secretion of kallikrein 10 protein by 10 primary tumor cultures including 3
      uterine serous papillary carcinomas, 2 endometrioid carcinomas, and 5 ovarian
      serous papillary tumors was measured using a sensitive ELISA. Finally, kallikrein
      10 concentration in 75 serum and plasma samples from 22 healthy women, 20 women
      with benign diseases, 21 women with endometrioid carcinomas, and 12 uterine
      serous papillary carcinoma patients was studied. RESULTS: Kallikrein 10 gene
      expression levels were significantly higher in uterine serous papillary carcinoma
      when compared with normal endometrial cell biopsies (mean copy number by real
      time polymerase chain reaction = 743 versus 1.4; uterine serous papillary
      carcinoma versus endometrioid carcinoma: P < .02). In vitro kallikrein 10
      secretion was detected in all primary uterine serous papillary carcinoma cell
      lines tested (mean = 2.7 microg/L), and the secretion levels were not
      significantly different to those found in primary ovarian serous papillary tumor
      cultures (mean 4.2 microg/L). In contrast, no kallikrein 10 secretion was
      detectable in primary endometrioid carcinomas. Kallikrein 10 serum and plasma
      concentrations (microg/L; mean +/- SEM) among normal healthy females (0.6 +/-
      0.04), patients with benign diseases (0.6 +/- 0.06), and patients with
      endometrioid carcinomas (0.7 +/- 0.06) were not significantly different. In
      contrast, serum and plasma kallikrein 10 values in uterine serous papillary
      carcinoma patients (1.2 +/- 0.1) were significantly higher than those in the non
      cancer group (P = .002), benign group (P = .002), and endometrioid carcinoma
      patients (P = .005). CONCLUSION: Kallikrein 10 is highly expressed in uterine
      serous papillary carcinoma, and it is released in the plasma and serum of uterine
      serous papillary carcinoma patients. Kallikrein 10 may represent a novel
      biomarker for uterine serous papillary carcinoma.

PMID- 16647914
TI  - Mensendieck somatocognitive therapy as treatment approach to chronic pelvic pain:
      results of a randomized controlled intervention study.
AB  - OBJECTIVE: The etiology of chronic pelvic pain is disputed and multifactorial. We
      studied the effect of Mensendieck somatocognitive therapy aimed at reducing
      physical pain by changing posture, movement and respiration patterns combined
      with standard gynecological treatment. STUDY DESIGN: Women with chronic pelvic
      pain unexplained by pelvic pathology were randomized into 2 groups: (1) standard
      gynecological treatment and (2) gynecological treatment plus somatocognitive
      therapy. A Mensendieck test of motor function (posture, movement, gait, sitting
      posture, respiration) and a visual analogue score of pain were obtained before
      and after the 90-day treatment period. RESULTS: The test results of patients
      treated by standard gynecological measures were unchanged (nonsignificant). By
      contrast, the patients receiving somatocognitive therapy in addition improved
      scores by 25% to 60% for all motor functions (P < .01, largest improvement for
      respiration, up from average 2.98 [SEM 0.30] to 4.72 [0.37]), and pain scores
      reduced by 50% (down from 5.60 [0.40] to 2.89 [0.40], P < .01). CONCLUSION:
      Mensendieck somatocognitive therapy combined with standard gynecological care
      improved pain experience and motor functions of women with chronic pelvic pain
      better than gynecological treatment alone.

PMID- 16647915
TI  - Venous thromboembolism during pregnancy and the postpartum period: incidence,
      risk factors, and mortality.
AB  - OBJECTIVE: The purpose of this study was to estimate the incidence, risk factors,
      and mortality from pregnancy-related venous thromboembolism. STUDY DESIGN: The
      Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of
      the Agency for Healthcare Research and Quality for the years 2000 to 2001 was
      queried for all pregnancy-related discharges with a diagnosis of venous
      thromboembolism. RESULTS: The rate of venous thromboembolism was 1.72 per 1000
      deliveries with 1.1 deaths per 100,000. The risk of venous thromboembolism was
      38% higher for women ages 35 and older and 64% higher for black women. Other
      significant risk factors included thrombophilia, lupus, heart disease, sickle
      cell disease, obesity, fluid and electrolyte imbalance, postpartum infection, and
      transfusion. The risk factor with the highest odds ratio, 51.8 (38.7-69.2) was
      thrombophilia. CONCLUSION: The incidence of pregnancy-related venous
      thromboembolism was higher than generally quoted. Women ages 35 and older, black
      women, and women with certain medical conditions and obstetric complications
      appear to be at increased risk.

PMID- 16647916
TI  - Maternal periodontal disease in early pregnancy and risk for a small-for
      gestational-age infant.
AB  - OBJECTIVE: The objective of the study was to determine whether periodontal
      disease is associated with delivery of a small-for-gestational-age infant. STUDY
      DESIGN: In a prospective study of oral health, periodontal disease was
      categorized as health, mild, or moderate/severe on the basis of clinical
      criteria. Small for gestational age was defined as birth weight less than the
      10th percentile for gestational age. A risk ratio (95th percentile confidence
      interval) for a small-for-gestational-age infant among women with moderate or
      severe periodontal disease was calculated. RESULTS: Sixty-seven of 1017 women
      (6.6%) delivered a small-for-gestational-age infant, and 143 (14.3%) had moderate
      or severe periodontal disease. The small-for-gestational-age rate was higher
      among women with moderate or severe periodontal disease, compared with those with
      health or mild disease (13.8% versus 3.2% versus 6.5%, P < .001). Moderate or
      severe periodontal disease was associated with a small-for-gestational-age
      infant, a risk ratio of 2.3 (1.1 to 4.7), adjusted for age, smoking, drugs,
      marital and insurance status, and pre-eclampsia. CONCLUSION: Moderate or severe
      periodontal disease early in pregnancy is associated with delivery of a small-for
      gestational-age infant. Understanding the mechanism of periodontal disease
      associated adverse pregnancy outcomes could lead to interventions to improve
      fetal growth.

PMID- 16647917
TI  - Intrinsic racial differences in the risk of cesarean delivery are not explained
      by differences in caregivers or hospital site of delivery.
AB  - OBJECTIVE: This study was undertaken to assess whether racial differences in the
      risk of cesarean delivery result from differing practices of their caregivers or
      the hospitals at which they deliver. STUDY DESIGN: A retrospective cohort study
      was performed using the Perinatal Database of the Memorial Health Care System.
      Logistic regression was used to estimate the risk of primary cesarean delivery
      among patients eligible for labor. The contribution of hospital and physician
      level cluster correlation was evaluated using fixed and random effects regression
      models. RESULTS: Compared with white patients, black and Hispanic patients were
      75% and 22% more likely to undergo primary cesarean delivery. Further adjustment
      for hospital and physician level cluster correlation resulted in persistently
      increased risks of primary cesarean delivery in black (54%) and Hispanic patients
      (12%). CONCLUSION: Hospital site of delivery and individual physician practices
      do not fully explain racial differences in the risk of primary cesarean delivery.

PMID- 16647918
TI  - Plurality-dependent risk of severe intraventricular hemorrhage among very low
      birth weight infants and antepartum corticosteroid treatment.
AB  - OBJECTIVE: This study was undertaken to compare the effect of antenatal
      corticosteroid therapy on the risk for severe intraventricular hemorrhage (IVH
      grade III-IV) in preterm singleton and multiple very low birth weight (VLBW)
      infants. STUDY DESIGN: The occurrence of severe IVH was recorded in 5022
      singleton, 2032 twin, and 582 triplet infants, delivered at 24 to 32 weeks'
      gestation, registered in the Israeli National VLBW infant database. Antenatal
      corticosteroid therapy was defined as complete, partial, or none. RESULTS: The
      incidence of IVH grade III-IV ranged from 6.8% among singletons receiving
      complete course to 29.3% in triplets without antenatal corticosteroid treatment.
      Complete treatment significantly reduced the incidence of IVH in all plurality
      groups. The adjusted risk for IVH among multiple infants who received a complete
      course compared with singletons was not significantly different, odds ratio (OR)
      1.3, 95% CI 1.0-1.7 for twins and OR 1.5, 95% CI 0.9-2.3 for triplets.
      CONCLUSION: Complete course of antenatal corticosteroid therapy was independently
      associated with decreased risk for severe IVH in singleton and in multiple
      preterm VLBW infants.

PMID- 16647919
TI  - Signaling via the type I IL-1 and TNF receptors is necessary for bacterially
      induced preterm labor in a murine model.
AB  - OBJECTIVE: We have shown previously that interleukin 1 (IL-1) signaling is not
      necessary for bacterially induced preterm delivery in mice. We now test whether
      combined signaling of IL-1 and tumor necrosis factor (TNF) is critical for this
      process. STUDY DESIGN: Female mice lacking the type I receptors for IL-1 and TNF
      (Il1r1/Tnfrsf1a double-knockouts) and normal controls underwent intrauterine
      inoculation with killed Escherichia coli bacteria on day 14.5 of a 19- to 20-day
      gestation. Preterm delivery rates within 48 hours were recorded and gene
      expression was analyzed by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: Il1r1/Tnfrsf1a double-knockout mice had significantly lower rates
      of preterm delivery than controls (8% vs 69% with 7 x 10(7) bacteria, P = .002,
      and 52% vs 81% with 1.4 x 10(8) bacteria, P = .003) and significantly lower
      myometrial levels of cyclooxygenase (COX)-2, but not COX-1 mRNA. There were no
      genotype- or treatment-related differences in cervicovaginal and lower uterine
      expression of mRNAs for a variety of genes associated with cervical ripening.
      CONCLUSION: The combination of IL-1 and TNF signaling plays a critical role in
      bacterially induced labor and myometrial COX-2 production in the mouse. Cervical
      gene expression patterns during bacterially induced preterm labor suggest
      fundamental differences from spontaneous term labor in the cervical ripening
      process.

PMID- 16647920
TI  - Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and
      intrauterine growth restriction.
AB  - OBJECTIVE: The prototypic long pentraxin pentraxin 3 is a new candidate marker
      for inflammatory conditions reflecting the involvement of the vascular bed.
      Endothelial dysfunction is a prominent feature of preeclampsia as a result of
      excessive maternal systemic inflammation. We investigated pentraxin 3 levels in
      preeclampsia and intrauterine growth restriction, pregnancy conditions related to
      altered placentation. STUDY DESIGN: We cross-sectionally studied nonpregnant
      women (n = 20); normal pregnancies in the first (n = 8), second (n = 10), and
      third (n = 26) trimester of pregnancy; 20 pregnancies complicated by
      preeclampsia; and 16 pregnancies complicated by intrauterine growth restriction.
      Maternal plasma samples were analyzed and pentraxin 3 determined by enzyme-linked
      immunosorbent assay. Pattern and site of placental expression of pentraxin 3 were
      studied by immunohistochemistry. RESULTS: In normal pregnancies pentraxin 3
      concentrations were significantly higher than nonpregnant women and did not
      change among the 3 trimesters. Significantly higher levels of pentraxin 3 were
      found in preeclampsia (median values 13.8 versus 2.2 ng/mL; P < .001), compared
      with normal pregnancies. Intrauterine growth restriction pregnancies showed
      intermediate levels between normal and preeclamptic patients, but this difference
      was not significant, compared with normal pregnancies (median values 3.9 versus
      2.2 ng/mL). No significant difference of pentraxin 3 levels was found between
      mild and severe preeclampsia. CONCLUSION: Elevated maternal plasma levels of
      pentraxin 3 in preeclamptic versus normal pregnancies could represent a marker of
      altered endothelial function, typical of preeclampsia.

PMID- 16647921
TI  - Early and late onset fetal microphthalmia.
AB  - OBJECTIVE: The purpose of this study was to present sonographic and pathologic
      findings in early and late onset fetal microphthalmia. STUDY DESIGN: Fetal
      sonography was prospectively performed in 30,989 consecutive pregnancies at 14 to
      24 weeks' gestation. In addition, we retrospectively reevaluated US recordings of
      4 fetuses from other hospitals, in which normal eyes were observed in early and
      midgestation and microphthalmia was diagnosed only in the third trimester of
      pregnancy or after birth. RESULTS: Microphthalmia was detected in 13 fetuses in
      the prospective group. Twelve of 13 had additional structural and chromosomal
      anomalies. Termination of pregnancy was performed in 12 cases. In the
      retrospective group of late onset microphthalmia we confirmed the normal eye
      measurements performed in the early and midpregnancy. Severe vision impairment or
      blindness was noted in 3 of these children, while the fourth pregnancy was
      terminated. CONCLUSION: Normal measurements of the fetal eyes in early and
      midpregnancy do not exclude the possibility of subsequent development of
      microphthalmia.

PMID- 16647922
TI  - Maternal characteristics and cervical length in the prediction of spontaneous
      early preterm delivery in twins.
AB  - OBJECTIVE: The purpose of this study was to examine the value of combining
      maternal characteristics and measurement of cervical length at 22 to 24 weeks in
      the prediction of spontaneous early preterm delivery. STUDY DESIGN: Cervical
      length was measured by transvaginal sonography at 22 to 24 weeks in 1163 twin
      pregnancies attending for routine antenatal care. Logistic regression analysis
      was used to examine the effect of maternal demographic characteristics and
      cervical length on the risk of spontaneous early preterm delivery. RESULTS: The
      rate of spontaneous delivery before 32 weeks was 6.5%. The rate of early delivery
      was inversely related to cervical length, and for a false-positive rate of 10%,
      the detection rate of early delivery was 65.3%. The respective detection rate for
      maternal characteristics and obstetric history was 26.4%. Logistic regression
      analysis demonstrated that the only significant independent predictor of
      spontaneous early delivery was cervical length. CONCLUSION: In twins, the
      prediction of spontaneous early preterm delivery by measurement of cervical
      length at 22 to 24 weeks is not improved by maternal characteristics.

PMID- 16647923
TI  - Bacteriuria in pregnant women with sickle cell trait.
AB  - OBJECTIVE: The purpose of this study was to compare the following outcome
      variables in pregnant patients with sickle cell trait and matched pregnant
      control patients: asymptomatic bacteriuria, acute cystitis, urinary pathogens
      that were present, and pyelonephritis. STUDY DESIGN: This was a retrospective
      cohort study that was conducted at a university clinic. Pregnant patients with
      sickle cell trait (n = 455) were matched with control patients (n = 448) for
      race, age, gestational age at entry into prenatal care, and number of prenatal
      visits. RESULTS: Women with sickle cell trait received urine testing
      significantly more often. There was no difference in the incidence of positive
      urine cultures, urinary pathogens, or asymptomatic bacteriuria among the
      comparison groups. Sickle cell trait carriers had significantly higher rates of
      pyelonephritis, but many affected patients had risk factors, such as previous
      pyelonephritis or noncompliance with therapy. CONCLUSION: Sickle cell trait
      carriers were no more susceptible to acute cystitis and asymptomatic bacteriuria
      than were the control patients. On the basis of these data, we outline
      recommendations for urinary screening and pyelonephritis prevention in pregnant
      patients with sickle cell trait.

PMID- 16647924
TI  - Effect of magnesium sulfate on contractile force and intracellular calcium
      concentration in pregnant human myometrium.
AB  - OBJECTIVE: This study was undertaken to evaluate the effects of magnesium sulfate
      (MgSO4) on contractile force and increases in free intracellular calcium
      concentration ([Ca2+]i) in human myometrial strips from pregnant women. STUDY
      DESIGN: Simultaneous measurements of isometric tension and [Ca2+]i were measured
      in myometrial strips obtained at the time of cesarean delivery from pregnant
      nonlaboring women at term with the use of a fluorescence spectrometer equipped
      with a displacement force transducer. Changes in [Ca2+]i were measured with fura
      2, a Ca(2+)-sensitive fluorescent probe. Myometrial strips were exposed to MgSO4
      (5 or 10 mmol/L) for 5, 10, 20, and 30 minutes and observed for spontaneous
      contractions or stimulated with either oxytocin (OT; 0.1 micromol/L) or potassium
      chloride (KCl; 90 mmol/L). RESULTS: MgSO4 reduced spontaneous, OT, and KCl-evoked
      contractions and increases in [Ca2+]i in a time and concentration-dependent
      manner. After 20 minutes exposure to 5 mmol/L MgSO4, the OT-elicited changes in
      contractile response and [Ca2+]i were significantly decreased. MgSO4 did not
      change [Ca2+]i/force relationship of the responses to OT or KCl, or during
      spontaneous activity. CONCLUSION: At a pharmacologic concentration (5 mmol/L),
      MgSO4 inhibits contractile response and [Ca2+]i in pregnant human myometrial
      strips by a pattern that is consistent with both extra- and intracellular
      mechanisms. At a suprapharmacologic concentration (10 mmol/L), the more immediate
      effect of MgSO4 is consistent with an extracellular mechanism. MgSO4 does not
      appear to interfere at the level of the calcium-calmodulin interface, since the
      [Ca2+]i/force relationship was not changed.

PMID- 16647925
TI  - Mifepristone-induced cervical ripening: structural, biomechanical, and molecular
      events.
AB  - OBJECTIVE: The purpose of this study was to assess the structural, biomechanical,
      and biochemical effects of mifepristone-induced progesterone withdrawal on the
      rat cervix to identify possible mechanisms by which mifepristone incites cervical
      ripening. STUDY DESIGN: After the administration of mifepristone, cervical
      tensile strength was determined by the cervical creep method. With polarized
      light microscopy and transmission electron microscopy, collagen organization and
      microstructure were quantified. Matrix metalloproteinase expression was assessed
      by Western Blot and Real-time reverse transcriptase-polymerase chain reaction.
      RESULTS: Mifepristone induced a decrease in cervical tensile strength at mid
      gestation that was associated with a decrease in collagen organization.
      Additionally, mifepristone led to collagen fragmentation with a significant
      decrease in fibril length and diameter, although fibril bundling remained
      unaffected. Matrix metalloproteinase-2 expression increased after the
      administration of mifepristone. CONCLUSION: Mifepristone-induced cervical
      ripening is associated with collagen degradation, and the collagenase activity of
      matrix metalloproteinase-2 may play a role in this process.

PMID- 16647926
TI  - Effect of patient age on increasing morbidity and mortality following
      urogynecologic surgery.
AB  - OBJECTIVE: The purpose of this study was to estimate the effect of age on the
      risk of in-hospital mortality and morbidity following urogynecologic surgery and
      to compare risks associated with obliterative versus reconstructive procedures
      for prolapse in elderly women. STUDY DESIGN: We conducted a retrospective cohort
      study utilizing data from 1998 to 2002 from the Nationwide Inpatient Sample.
      Multivariable logistic regression was performed to obtain odds ratios estimating
      the effect of age on risk of death and complications, adjusting for comorbidities
      and demographic factors. RESULTS: There were 264,340 women in our study
      population. Increasing age was associated with higher mortality risks per 1000
      women (< 60 years, 0.1; 60-69 years, 0.5; 70-79 years, 0.9; > or = 80 years, 2.8;
      P < .01) and higher complication risks per 1000 women (< 60 years, 140; 60-69
      years, 130; 70-79 years, 160; > or = 80 years, 200; P < .01). Using multivariable
      logistic regression, increasing age was associated with an increased risk of
      death (60-69 years, odds ratio [OR] 3.4 [95% CI 1.7-6.9]; 70-79 years, OR 4.9
      [95% CI 2.2-10.9]; > or = 80 years, OR 13.6 [95% CI 5.9-31.4]), compared with
      women < 60 years. The risk of peri-operative complications was also higher in
      elderly women 80 years of age and older (OR 1.4 [95% CI 1.3-1.5]) compared with
      younger women. Elderly women 80 years and over who underwent obliterative
      procedures had a lower risk of complication compared with those who underwent
      reconstructive procedures for prolapse (17.0% vs 24.7%, P < .01). CONCLUSION:
      Although the absolute risk of death is low, elderly women have a higher risk of
      mortality and morbidity following urogynecologic surgery.

PMID- 16647927
TI  - Mesh erosion in abdominal sacral colpopexy with and without concomitant
      hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to examine risk factors for mesh
      erosion, including concomitant hysterectomy, in abdominal sacral colpopexies.
      STUDY DESIGN: We conducted a retrospective cohort study of 313 women who
      underwent an abdominal sacral colpopexy. Data regarding patient demographics,
      operative techniques, length of follow-up, postoperative complications, and mesh
      erosion were collected. RESULTS: Of 313 subjects, 101 (32.3%) had concomitant
      hysterectomies and 212 (67.7%) had had previous hysterectomies. The overall rate
      of mesh erosion was 5.4%. In bivariate analysis, concomitant hysterectomy was not
      associated with erosion (6.9% vs 4.7% previous hysterectomy, P = .42); however,
      estrogen therapy was an effect modifier. In women on estrogen, hysterectomy (OR
      4.9, CI 1.2-19.7) and anterior imbrication (OR 5.6, CI 1.1-28.6) were associated
      with mesh erosion. No risk factors were identified in women not on estrogen.
      CONCLUSION: In women on estrogen therapy, hysterectomy was associated with mesh
      erosion in abdominal sacral colpopexy.

PMID- 16647928
TI  - Women seeking treatment for advanced pelvic organ prolapse have decreased body
      image and quality of life.
AB  - OBJECTIVE: Women who seek treatment for pelvic organ prolapse strive for an
      improvement in quality of life. Body image has been shown to be an important
      component of differences in quality of life. To date, there are no data on body
      image in patients with advanced pelvic organ prolapse. Our objective was to
      compare body image and quality of life in women with advanced pelvic organ
      prolapse with normal controls. STUDY DESIGN: We used a case-control study design.
      Cases were defined as subjects who presented to a tertiary urogynecology clinic
      with advanced pelvic organ prolapse (stage 3 or 4). Controls were defined as
      subjects who presented to a tertiary care gynecology or women's health clinic for
      an annual visit with normal pelvic floor support (stage 0 or 1) and without
      urinary incontinence. All patients completed a valid and reliable body image
      scale and a generalized (Short Form Health Survey) and condition-specific (Pelvic
      Floor Distress Inventory-20) quality-of-life scale. Linear and logistic
      regression analyses were performed to adjust for possible confounding variables.
      RESULTS: Forty-seven case and 51 control subjects were enrolled. After
      controlling for age, race, parity, previous hysterectomy, and medical
      comorbidities, subjects with advanced pelvic organ prolapse were more likely to
      feel self-conscious (adjusted odds ratio 4.7; 95% confidence interval 1.4 to 18,
      P = .02), less likely to feel physically attractive (adjusted odds ratio 11; 95%
      confidence interval 2.9 to 51, P < .001), less likely to feel feminine (adjusted
      odds ratio 4.0; 95% confidence interval 1.2 to 15, P = .03), and less likely to
      feel sexually attractive (adjusted odds ratio 4.6; 95% confidence interval 1.4 to
      17, P = .02) than normal controls. The groups were similar in their feeling of
      dissatisfaction with appearance when dressed, difficulty looking at themselves
      naked, avoiding people because of appearance, and overall dissatisfaction with
      their body. Subjects with advanced pelvic organ prolapse suffered significantly
      lower quality of life on the physical scale of the SF-12 (mean 42; 95% confidence
      interval 39 to 45 versus mean 50; 95% confidence interval 47 to 53, P < .009).
      However, no differences between groups were noted on the mental scale of the SF
      12 (mean 51; 95% confidence interval 50 to 54 versus mean 50; 95% confidence
      interval 47 to 52, P = .56). Additionally, subjects with advanced pelvic organ
      prolapse scored significantly worse on the prolapse, urinary, and colorectal
      scales and overall summary score of Pelvic Floor Distress Inventory-20 than
      normal controls (mean summary score 104; 95% confidence interval 90 to 118 versus
      mean 29; 95% confidence interval 16 to 43, P < .0001), indicating a decrease in
      condition-specific quality of life. Worsening body image correlated with lower
      quality of life on both the physical and mental scales of the SF-12 as well as
      the prolapse, urinary, and colorectal scales and overall summary score of Pelvic
      Floor Distress Inventory-20 in subjects with advanced pelvic organ prolapse.
      CONCLUSION: Women seeking treatment for advanced pelvic organ prolapse have
      decreased body image and overall quality of life. Body image may be a key
      determinant for quality of life in patients with advanced prolapse and may be an
      important outcome measure for treatment evaluation in clinical trials.

PMID- 16647929
TI  - Magnetic resonance imaging of the levator ani in the squirrel monkey: a
      comparison of muscle volume between a cohort with pelvic organ prolapse and
      matched normals.
AB  - OBJECTIVE: Magnetic resonance imaging was used to test whether squirrel monkeys
      with pelvic organ prolapse have reduced pelvic muscle volumes, compared with
      matched normals. STUDY DESIGN: Levator ani and obturator internus volumes
      obtained from T1-weighted axial scans of matched groups were measured. Muscle
      volumes and weights were compared for animals necropsied after magnetic resonance
      imaging. RESULTS: Two observers concurred on measures of levator ani and
      obturator internus (Kendal tau > or = 0.60 with P < .003). Levator ani volume was
      related to mass (R2 = 0.62, P = .0009). Animals with pelvic organ prolapse did
      not differ (P = .67, Wilks multivariate test) from those without pelvic organ
      prolapse in age, parity, and weight. Levator ani differed between groups (pelvic
      organ prolapse = 520 mm3 versus normals = 392 mm3, P = .015) and not sides (P =
      .80). The obturator internus did not differ between groups (P = .29) or sides (P
      = .72). CONCLUSION: Magnetic resonance imaging demonstrates that levator ani
      volumes in parous squirrel monkeys with pelvic organ prolapse were not reduced,
      suggesting that prolapse is not related to pelvic muscle size reduction in this
      species.

PMID- 16647930
TI  - Biomechanical characterization of vaginal versus abdominal surgical wound healing
      in the rabbit.
AB  - OBJECTIVE: The objective of the study was to compare biomechanical properties of
      vaginal versus abdominal surgical wound healing in the rabbit. STUDY DESIGN:
      Bilateral 6-mm full-thickness circular segments were excised from the vagina and
      abdominal skin in 38 New Zealand White female rabbits. Animals were killed 0, 4,
      7, 10, 14, 21, 28, and 35 days after wounding, and the wounds were assessed for
      surface area and tensile properties. RESULTS: Wound closure and scar contraction
      were significantly faster in the vagina than the abdomen (P = .001). Baseline
      tensile strength (P = .05), modulus (P = .001), and tensile energy to break (P =
      .18) were higher in the abdomen, whereas maximal tissue elongation was higher in
      the vagina (P = .13). After wounding, a drop in tensile strength, modulus, and
      tensile energy to break was observed in both tissues through postwounding day 4,
      followed by a progressive recovery of these properties. A progressive loss of
      elasticity was noted in both tissues after wounding. CONCLUSION: The surgical
      wound closes and contracts faster in the rabbit vagina than in its abdomen.
      Although these tissues have different biomechanical properties at baseline, they
      regenerate their tensile strength and lose their elasticity at a similar rate.

PMID- 16647931
TI  - The incidence of ureteral obstruction and the value of intraoperative cystoscopy
      during vaginal surgery for pelvic organ prolapse.
AB  - OBJECTIVE: The objective of the study was to determine the incidence of ureteral
      obstruction during vaginal surgery for pelvic organ prolapse and the accuracy and
      efficacy of intraoperative cystoscopy. STUDY DESIGN: The study was a
      retrospective review of 700 consecutive patients who underwent vaginal surgery
      for anterior and/or apical pelvic organ prolapse with universal intraoperative
      cystoscopy. RESULTS: Thirty-seven patients (5.3%) had no spillage of dye from 1
      or both ureters intraoperatively. The false-positive and negative cystoscopy
      rates were 0.4% and 0.3%, respectively. Thus, the true incidence of
      intraoperative ureteral obstruction was 5.1%. Intraoperative cystoscopy was
      accurate in 99.3% of cases, with a sensitivity and specificity of 94.4% and
      99.5%, respectively. Suture removal relieved ureteral obstruction in 88% of
      cases. Six subjects (0.9%) had true ureteral injuries. CONCLUSION: Vaginal
      surgery for anterior and/or apical pelvic organ prolapse is associated with an
      intraoperative ureteral obstruction rate of 5.1%. Intraoperative cystoscopy
      accurately detects ureteral obstruction and allows for relief of obstruction in
      the majority of cases.

PMID- 16647932
TI  - Outcomes with porcine graft placement in the anterior vaginal compartment in
      patients who undergo high vaginal uterosacral suspension and cystocele repair.
AB  - OBJECTIVE: The purpose of this study was to prospectively assess the cases of
      patients who had undergone a high uterosacral suspension and anterior repair with
      anterior compartment placement of porcine dermis graft. STUDY DESIGN: Thirty-six
      patients who underwent transvaginal high uterosacral suspension and cystocele
      repair with graft augmentation from June 2001 to July 2004 were identified from
      the University of Alabama at Birmingham Genitourinary Disorders database.
      Analysis included the pre- and postoperative Pelvic Organ Prolapse Quantification
      examinations and incontinence impact questionnaire-7/urogenital distress
      inventory-6. RESULTS: Mean Pelvic Organ Prolapse Quantification Ba improved from
      +3.3 +/- 2.2 cm to -0.6 +/- 1.7 cm (P < .01). Postoperative Ba was prolapse stage
      II or greater in 50% of subjects. Mean incontinence impact questionnaire-7 scores
      improved from 36.2 +/- 31.9 to 15.6 +/- 26.2 (P < .01), as did mean urogenital
      distress inventory-6 scores from 58.2 +/- 26.8 to 23.8 +/- 22.6 (P < .01).
      CONCLUSION: Significant improvements in Pelvic Organ Prolapse Quantification
      measures, urinary symptoms, and the impact of incontinence were seen after the
      operation. However, a significant proportion of patients had Pelvic Organ
      Prolapse Quantification stage II prolapse or greater, which made it unclear
      whether graft use confers a significant advantage.

PMID- 16647933
TI  - Responsiveness of the Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor
      Impact Questionnaire (PFIQ) in women undergoing vaginal surgery and pessary
      treatment for pelvic organ prolapse.
AB  - OBJECTIVE: This study was undertaken to evaluate the responsiveness of the Pelvic
      Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ) in
      women with pelvic organ prolapse undergoing surgical and nonsurgical management.
      STUDY DESIGN: The responsiveness of the prolapse, urinary and colorectal scales
      of the PFDI and PFIQ were assessed in 2 independent populations: (1) 42 women
      with stage II or greater prolapse enrolled in an ongoing multicenter randomized
      trial comparing 2 different pessaries (Pessary group) and (2) 64 women with stage
      III or greater prolapse who underwent vaginal reconstructive surgery (Surgery
      group). All subjects completed the PFDI and PFIQ at baseline and again either 3
      months (Pessary group) or 6 months (Surgery group) after initiation of treatment.
      Responsiveness was assessed with standardized response mean (SRM), effect size
      (ES), and the paired t test. RESULTS: In the Pessary group, there was a
      significant improvement in the prolapse and urinary scales of the PFDI, with each
      demonstrating moderate responsiveness (prolapse: SRM 0.69, ES 0.68; urinary: SRM
      0.57, ES: 0.50, P < .001 for each). The colorectal scale of the PFDI and each of
      the 3 scales of the PFIQ demonstrated no significant change in scores with
      pessary use. In the Surgery group, there was a significant improvement in the
      prolapse, urinary, and colorectal scales of both the PFDI and PFIQ (P < .01 for
      each). The prolapse and urinary scales of the PFDI demonstrated excellent
      responsiveness with SRM and ES 1.20 or greater for the prolapse scale and equal
      to1.05 for the urinary scales. The colorectal scale of the PFDI and the urinary
      and prolapse scales of the PFIQ demonstrated moderate responsiveness (SRM 0.61
      0.70 and ES 0.56-0.60) after surgery. Subjects who had a recurrence of their
      prolapse develop after surgery (6%) had significantly less improvement in the
      prolapse scale of the PFDI than those who did not. After controlling for
      preoperative prolapse stage and baseline quality of life scores, subjects in the
      Surgery group had significantly greater improvement in each of the scales of the
      PFDI and the prolapse and urinary scales of the PFIQ than did the Pessary group
      (P < .05 for each). CONCLUSION: The PFDI and PFIQ are responsive to change in
      women undergoing surgical and nonsurgical treatment for pelvic organ prolapse.
      The PFDI is more responsive than the PFIQ.

PMID- 16647934
TI  - Sex hormone-binding globulin--a surrogate marker for the prothrombic effects of
      combined oral contraceptives.

PMID- 16647935
TI  - Prophylactic antibiotics in cesarean section.

PMID- 16647939
TI  - Keepsake ultrasounds: more than just another pretty face.

PMID- 16647940
TI  - Unsuccessful attempt to demonstrate progesterone's bone formation actions.

PMID- 16647942
TI  - Dissection bias in subperitoneal pelvic anatomy.

PMID- 16647943
TI  - Proceedings from the 26th Annual Meeting of the American Urogynecologic Society,
      Atlanta, Georgia, USA, September 15-17, 2005.

PMID- 16647944
TI  - Loud and clear now-advocacy and academic surgery.

PMID- 16647945
TI  - INCOMING!--A web tracking application for PACU and post-surgical patients.
AB  - BACKGROUND: Capacity constraints necessitate improving hospital efficiency. An
      integrated real time system facilitating patient flow between the post-anesthesia
      care unit (PACU) and surgical ward would ease PACU workload by reducing the
      effort of discharging patients. METHODS: We developed INCOMING!, a web-based
      platform that monitors patient progress from the operating room to the PACU.
      INCOMING! integrates available data, automatically determining when a patient
      enters the PACU. An automated paging system alerts clinical unit managers to
      'pull' their patients from the PACU after a set recovery period. General surgery
      patients were included in the INCOMING! system in late 2004 with paging added in
      mid-March 2005. Mean PACU length of stay was calculated for the intervention
      group (general surgery patients with INCOMING!) and compared to a control group
      (general surgery patients without INCOMING!) and an orthopedic surgery group
      before and after paging. RESULTS: The system successfully gathers data and
      generates automated pages when events occur. After paging, there was a
      significant difference between the orthopedic surgery control group and the
      general surgery intervention group (235 min versus 185 min, P = 0.001). The mean
      PACU LOS decreased in the INCOMING! intervention group by 26 min while the mean
      LOS increased by 28 min in the general surgery control group (P = 0.27).
      CONCLUSION: Pilot implementation demonstrates that INCOMING! performs the desired
      integration and automatic notification. Given the minimal cost and potential
      large gains from a wider deployment, we plan to implement the system for all PACU
      patients and all post-PACU care units.

PMID- 16647946
TI  - SEL1L expression in non-small cell lung cancer.
AB  - SEL1L gene product plays a role in cell transformation and tumor progression in
      human breast, pancreas, esophageal, and prostate cancer. SEL1L expression was
      evaluated in a series of 76 surgically resected non-small cell lung carcinomas to
      investigate its clinical significance. SEL1L is scarcely detectable in normal
      lung, whereas in the initial stages of cell transformation, it becomes
      consistently expressed with evident staining in bronchial squamous metaplasia and
      in associated dysplastic changes. SEL1L immunoreactivity can be detected both in
      the cytoplasm and less commonly in the nuclei; the subcellular location
      correlates with tumor histotype, with cytoplasmic immunoreactivity being most
      prevalent in squamous cell carcinomas (P = .0005) and nuclear immunoreactivity
      being associated with adenocarcinomas (P = .02). Nuclear import and export
      signals are present in the SEL1L coding sequence, justifying the different
      subcellular location of the protein. SEL1L immunoreactivity was inversely
      correlated with tumor grade (P = .05); when considering only the adenocarcinomas,
      a stronger association was found (P = .006). SEL1L messenger RNA and protein
      evaluation in lung cancer cell lines confirmed the expression of the gene and the
      dual subcellular location of the protein in lung tumors. The data here reported
      suggest that, in non-small cell lung carcinoma, SEL1L may be an indicator of cell
      transformation, thus having important biologic and clinical implications.

PMID- 16647947
TI  - p16 expression in relation to human papillomavirus in anogenital lesions.
AB  - Recent studies have revealed that cervical cancers associated with high-risk
      human papillomavirus (HPV) showed overexpression of the p16 protein, a cyclin
      dependent kinase inhibitor. The expression of this cell cycle regulator in
      lesions of the anogenital region in association with HPV physical status
      (episomal or integrated) has not been studied at the present time. In this
      report, immunohistochemical analysis of p16 and HPV detection by in situ
      hybridization were performed on 110 formalin-fixed and paraffin-embedded samples
      of anogenital lesions. The results showed strong diffuse p16 staining in all
      integrated high-risk HPV-positive lesions, whereas most episomal HPV-positive
      lesions or HPV-negative lesions showed no p16 immunostaining. However, there were
      a few HPV-negative lesions or lesions with episomal HPV harboring p16
      overexpression. On the other hand, some lesions were p16 negative while showing
      the presence of high-risk HPV in its episomal form. In conclusion, screening for
      p16 overexpression in cutaneomucous lesions of the anogenital region allowed good
      discrimination between HPV-integrated lesions and lesions harboring episomal HPV
      or no HPV. But p16 overexpression was not always predictive of the presence of
      high-risk HPV; moreover, absence of p16 immunostaining observed in some high-risk
      HPV lesions suggested that limiting the screening to p16 would exclude some
      patients harboring high-risk HPV from any follow-up.

PMID- 16647948
TI  - BRAF and c-kit gene copy number in mutation-positive malignant melanoma.
AB  - Activating mutations in BRAF or c-kit have been reported in malignant melanoma.
      Because the activating mutations are dominant, it has been assumed that they are
      heterozygous in the affected tumors. To test this, we have carefully examined the
      DNA sequencing electropherograms on 43 BRAF mutation-positive and 3 c-kit
      mutation-positive malignant melanomas to determine the ratio of the normal to
      mutant allele. Of the 43 BRAF mutation-positive tumors, we classified 26 as
      presumptive heterozygous. Eight cases were indeterminate. Surprisingly, 9 cases
      appeared to contain an excess of the mutant allele. BRAF fluorescence in situ
      hybridization on these 9 cases suggested the increased amount of the mutant BRAF
      allele was due to amplification (2 cases) or chromosome 7 polysomy (7 cases). We
      have previously described the presence of the c-kit-activating mutation, L576P,
      in 2 of 100 malignant melanomas. In this report, we have evaluated an additional
      53 cases and found 1 additional case that contained the L576P mutation.
      Evaluation of the DNA sequencing electropherograms from all 3 cases of L576P
      mutation-positive melanoma suggests a selective loss of the normal allele.
      Fluorescence in situ hybridization for c-kit on these 3 L576P mutation-positive
      tumors indicated that one showed slight amplification of the c-kit gene and the
      other 2 were present in a nonamplified diploid state. These results have
      important implications concerning the mechanism of oncogenesis in melanoma as
      well as in the response of the tumor to anticancer drugs targeting BRAF or c-kit.

PMID- 16647949
TI  - Molecular, cytogenetic, and immunophenotypic characterization of follicular
      lymphoma grade 3B; a separate entity or part of the spectrum of diffuse large B
      cell lymphoma or follicular lymphoma?
AB  - We studied a histological homogeneous group of 29 cases with the diagnosis of
      follicular lymphoma (FL) grade 3B (FL3Bs). In a previous study, we subdivided
      this group in 3 subgroups based on (1) aberrations of the 3q27 region, (2) lack
      of 3q27 and t(14;18), and (3) the presence of a t(14;18). In this study, we
      further characterized the FL3B lymphomas that are currently part of the spectrum
      of FL in the WHO classification, taking into account other cytogenetical
      aberrations, immunohistochemistry for P53, bcl2, bcl6, and CD10, rearrangement of
      the proto-oncogene myc, and mutation of the tumor suppressor gene TP53. With
      respect to P53, bcl2, bcl6 expression, myc rearrangement, and TP53 mutation, FL3B
      represents a homogeneous group. CD10 expression and gain of chromosome 7,
      considered to be typical FL markers, were more common in the FL3B t(14;18)
      positive subgroup. The lack of CD10 expression and gain of chromosome 7 in most
      cases in the other 2 subgroups suggest that those cases have a closer relation to
      diffuse large B-cell lymphomas.

PMID- 16647950
TI  - Identification of a 7.1-mega base pairs minimal deletion at 14q31.1-32.11 in
      adenocarcinomas of the gastroesophageal junction.
AB  - In a recent evaluation by comparative genomic hybridization, we demonstrated
      chromosome 14q31-32.1 to be frequently deleted in adenocarcinomas of the
      gastroesophageal junction. This suggests the presence of a tumor suppressor gene
      in the deleted region. In the present study, we have performed a detailed loss of
      heterozygosity analysis in 34 gastroesophageal junction adenocarcinomas and 1
      tumor-corresponding dysplastic Barrett's epithelium sample with 37 polymorphic
      microsatellite markers. Thirty-five markers are in the 14q24.3-32.33 region with
      a mean distance of 800 kilo base pairs. Of 34 tumor samples, 14 (41%) showed loss
      of 14q markers. We identified a minimal region of allelic loss of 7105440 base
      pairs between markers D14S1000 and D14S256 at cytogenetic location 14q31.1-32.11.
      Within this region, markers D14S1035, D14S55, D14S1037, D14S1022, D14S1052,
      D14S974, D14S73, D14S1033, D14S67, D14S68, and D14S1058 showed loss in all
      informative tumors with 14q loss. The region between markers D14S1000 and D14S256
      contains 7 known genes. The identification of this minimal deletion and the data
      base information on the genes present in this region facilitate the search for
      the candidate tumor suppressor gene(s).

PMID- 16647951
TI  - Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell
      lung carcinomas.
AB  - In this study, we sought to validate the importance of p63, CK5/CK6, CK7, and
      surfactant-A (SP-A) to classify 42 non-small cell lung cancers in autopsy and
      surgical resection specimens and to study the usefulness of these markers in
      distinguishing between squamous cell carcinomas and adenocarcinomas because of
      their different implications regarding treatment and prognosis. All
      adenocarcinoma cases were negative for p63; 9 (56.2%) of 16 were CK5/CK6
      positive, 16 (94.1%) of 17 were CK7 positive, and 4 (26.6%) of 15 were SP-A
      positive. In squamous cell carcinoma, 1 case was CK7 and SP-A positive and 14
      (77.8%) of 18 were p63 positive. The latter appears to be useful in
      differentiating squamous cell carcinoma from adenocarcinoma of the lung in small
      biopsies without keratinization or glandular differentiation; thus, for advanced
      stage cases, where there is no possibility of surgical resection and the
      treatment of choice is radiotherapy plus chemotherapy, we would be able to
      differentiate between the two histological types, establishing then a different
      therapy.

PMID- 16647952
TI  - Hereditary nephritis mimicking immune complex-mediated glomerulonephritis.
AB  - The defining ultrastructural features of hereditary nephritis are "basket weave"
      lamellation or thinning of glomerular basement membranes. Electron-dense deposits
      are not seen and immunofluorescence (IF) is generally negative. In this study, we
      report 5 cases of hereditary nephritis in which substantial amounts of glomerular
      electron-dense deposits were identified on electron microscopy, with
      corresponding positive IF staining in 4 cases, suggesting immune complex-mediated
      glomerulonephritis. However, no case had histological evidence of glomerular
      endocapillary or extracapillary proliferation or leukocyte infiltration typical
      of active glomerulonephritis. Four cases were diagnosed at outside institutions
      simply as forms of glomerulonephritis without considering the possibility of
      hereditary nephritis and were sent for consultation in contemplation of possible
      immunosuppressive therapy. All patients had negative serologies and no known
      underlying infectious or autoimmune disease; 4 patients had family history of
      hematuria or renal disease. The glomerular electron-dense deposits were
      predominantly mesangial (4 cases) and intramembranous (4 cases), as well as
      subepithelial (2 cases) or subendothelial (1 case). Corresponding IF positivity
      for immune reactants was identified in 4 cases, and IgG was the predominant
      immunoglobulin deposited. A characteristic feature was the tendency for deposits
      to form between the complex layers of glomerular basement membrane material,
      favoring a process of nonspecific entrapment of immune reactants within the
      thickened, lamellated basement membrane. In all cases, a diagnosis of hereditary
      nephritis was confirmed by demonstration of the characteristic loss of
      immunoreactivity for the alpha5 subunit of collagen IV (4 cases) or Goodpasture's
      antigen (1 case) in renal or epidermal basement membranes. These cases expand the
      spectrum of unusual pathological findings in hereditary nephritis and emphasize
      the potential for hereditary nephritis to mimic immune complex
      glomerulonephritis.

PMID- 16647953
TI  - Claudin-1 and claudin-2 differentiate fetal and embryonal components in human
      hepatoblastoma.
AB  - Claudins (CLDNs), a family of transmembrane proteins, are major constituents of
      tight junctions (TJs). They have been shown to be differentially regulated in
      malignant tumors and play a role in carcinogenesis and progression. We aimed to
      explain the molecular mechanism underlying the main epithelial components of
      hepatoblastomas (HBs) based on the composition of TJs. Fourteen formalin-fixed,
      paraffin-embedded surgical resection specimens were analyzed by
      immunohistochemistry for CLDN-1, -2, -3, -4, -7; proliferating cell nuclear
      antigen (PCNA); Ki-67; beta-catenin; cytokeratin-7 (CK-7); and hepatocyte
      specific antigen; messenger RNA was isolated for real-time reverse transcriptase
      polymerase chain reaction analysis of the CLDNs from dissected fetal and
      embryonal cell types. Significantly increased protein and messenger RNA
      expression of CLDN-1 and -2 was detected in the fetal compared with the embryonal
      component. Both cell types displayed negative or weak immunostainings for CLDN-3,
      -4, and -7. Hepatocyte-specific antigen was dominantly expressed in the fetal
      component. PCNA and Ki-67 labeling indices were significantly higher in embryonal
      compared with fetal cells. beta-catenin cytoplasmic/nuclear immunoreaction was
      frequent, although not showing significant differences between fetal and
      embryonal cells. Mutational analysis of beta-catenin detected mutation in two
      cases. Our results suggest that increased expression of CLDN-1 and -2
      characterizes the more differentiated fetal component in HBs and is a reliable
      marker for differentiating fetal and embryonal cell types in HBs. The results
      proved that the embryonal and fetal components of HBs differ in such important
      feature as the protein composition of TJs. The expression of CLDN-1 and -2 is
      inversely correlated with cell proliferation. The more aggressive, rapidly
      proliferating embryonal phenotype is associated with the decrease/loss of CLDN-1
      and -2. However, there are no data indicating association with the nuclear
      translocation of beta-catenin.

PMID- 16647954
TI  - The p75 neurotrophin receptor is widely expressed in conventional papillary
      thyroid carcinoma.
AB  - Papillary thyroid carcinomas (PTCs) are associated with alterations in several
      proto-oncogenes related with nervous system development and function, such as
      TrkA and RET, which are commonly rearranged in these carcinomas. The other
      oncogenic event recently identified in PTC is the BRAF V600E mutation. Because
      the role of TrkA was not completely elucidated in thyroid cancer
      ethiopathogenesis, we decided to study the expression of active, phosphorylated
      TrkA and of its coreceptor p75 neurotrophin receptor (p75 NTR) in a series of 92
      PTC (37 lesions of conventional PTC, 28 of follicular variant of PTC [FVPTC], and
      27 of other variants of PTC) as well as in 21 samples of normal thyroid and
      nonneoplastic thyroid lesions used as a controls. We observed neoexpression of
      p75 NTR in PTC, particularly in conventional PTC and in other variants of PTC
      displaying a papillary growth pattern, rather than in FVPTC. No immunoexpression
      of p75 NTR was observed in normal thyroid nor in nonneoplastic thyroid lesions.
      The cellular localization of p75 NTR immunoexpression was also significantly
      associated with the growth pattern of PTC, being much more frequently detected in
      an apical localization in PTC with papillary architecture than in PTC with a
      follicular or solid growth pattern. This apical localization of p75 NTR was
      significantly associated with the presence of BRAF V600E. No significant
      differences were detected between normal thyroid, nonneoplastic lesions, and PTC
      (or any PTC variant) regarding expression/activation of TrkA, thus suggesting
      that by itself and in contrast to p75 NTR, TrkA is not altered during PTC
      development.

PMID- 16647955
TI  - Reduced expression of claudin-7 correlates with invasion and metastasis in
      squamous cell carcinoma of the esophagus.
AB  - Claudins are transmembrane proteins that seal tight junctions, bind with
      peripheral protein zonula occludens (ZO)-1, and are known to play an important
      role in several normal tissues and cancers. However, the role of claudin-1 and
      claudin-7 expressions in esophageal squamous cell carcinoma remains to be
      clarified. In the present study, we confirmed the expressions of claudin-1,
      claudin-7, and ZO-1 in the prickle cell layer of the normal human esophageal
      squamous epithelium. The expressions of claudin-1 and claudin-7 at the invasive
      front of the esophageal squamous cell carcinoma were analyzed
      immunohistochemically to clarify their role in tumor progression. Reduced
      expression of claudin-7 at the invasive front of the esophageal cancer was
      significantly associated with the depth of invasion (P = .004), stage (P = .038),
      lymphatic vessel invasion (P = .001), and lymph node metastasis (P = .014). In
      contrast, significant association was not detected between claudin-1 expression
      and clinicopathologic factors except for histologic differentiation of the tumor
      (P = .0029). Comparison of claudin-7 expression at the invasive front of the
      primary tumor and its corresponding metastatic lymph nodes revealed significant
      reduction in claudin-7 expression in the metastatic lymph nodes (P = .007). These
      results suggest that the reduced expression of claudin-7 at the invasive front of
      esophageal squamous cell carcinoma may lead to tumor progression and subsequent
      metastatic events. Thus, claudin-7 can be a novel marker for the prediction of
      lymph node metastasis.

PMID- 16647956
TI  - p16(INK4a) promoter methylation and 9p21 allelic loss in colorectal carcinomas:
      relation with immunohistochemical p16(INK4a) expression and with tumor budding.
AB  - In colorectal carcinomas, p16(INK4a) inactivation is known to occur by allelic
      loss and by promoter methylation, but mutations are rare. p16(INK4a) is up
      regulated in tumor buds, and the consequent shutdown of proliferation may be a
      prerequisite for tumor budding. Fifty-seven colorectal carcinomas from a
      consecutive series were investigated. Using DNA from tissue homogenates,
      p16(INK4a) promoter methylation was seen in 17 of 57 tumors by methylation
      specific polymerase chain reaction, and this could be confirmed using DNA from
      laser-capture microdissected material in 16 of these cases. A total loss of
      immunohistochemical p16(INK4a) expression was seen in 6 of 17 tumors with
      promoter methylation. Quantification of immunohistochemical p16(INK4a) expression
      for the remaining 11 cases revealed statistically lower frequencies of expression
      as compared with cases without p16(INK4a) promoter methylation. 9p21 allelic loss
      was observed in 9 cases, but p16(INK4a) expression in these carcinomas was not
      reduced. Attempted linear regression of p16(INK4a) expression in tumor buds on
      the degree of tumor budding, as counted on pan-cytokeratin immunostains, did not
      show a correlation. p16(INK4a) promoter methylation can completely abrogate
      p16(INK4a) expression in colorectal carcinomas. In many cases, however, it has an
      appreciable but only modulatory influence on p16(INK4a) expression. Possibly,
      methylations are heterozygous, and/or mosaic in colorectal carcinomas and/or
      methylations are not totally stable but can be lost between carcinoma cell
      replication cycles. Up-regulation of p16(INK4a) does not seem to be a strict
      requirement for tumor budding, hence, the absence of a correlation.

PMID- 16647957
TI  - STAT 5a expression in the breast is maintained in secretory carcinoma, in
      contrast to other histologic types.
AB  - The 7 signal transducer and activator of transcription (STAT) molecules are
      responsible for the transcription of a variety of regulatory and differentiation
      proteins. STAT 5a is activated through a variety of mechanisms; in the breast,
      this is predominantly through binding of prolactin to its receptor. Previously,
      we showed that STAT 5a expression is decreased in atypical and malignant breast
      ductal epithelial cells. Interestingly, STAT 5a overexpression was observed in
      cells undergoing secretory change. In this study, secretory carcinomas were
      examined by immunohistochemistry for the presence of STAT 5a. In contrast to
      usual in situ or invasive ductal carcinoma, which lacked STAT 5a expression, all
      secretory carcinomas (11 invasive and 7 in situ, including 4 cases with both)
      expressed STAT 5a. No expression was seen in apocrine metaplasia or in other
      specialized breast carcinomas, such as mucinous or clear cell carcinoma. This
      retention of signal in the secretory carcinomas may be explained by the higher
      STAT 5a concentration present in cells undergoing secretory changes in general.
      Alternatively, STAT 5a expression may be related to the t(12;15)(p13;q25)
      chromosomal translocation, associated with certain pediatric tumors and recently
      demonstrated in many secretory carcinomas of the breast, which results in the
      expression of a tyrosine kinase through ETV6 and NTRK3 fusion. ETV6 also has been
      associated with the STAT 5a signaling pathway in another gene translocation and
      may be altering STAT 5a expression in secretory carcinomas. Breast cancer causes
      significant morbidity and mortality, and, regardless of the mechanism for
      retention of STAT 5a expression in this uncommon variant, the examination of STAT
      5a will aid our understanding of normal and abnormal breast tissues.

PMID- 16647958
TI  - Differential expression of Epstein-Barr virus-encoded RNA and several tumor
      related genes in various types of nasopharyngeal epithelial lesions and
      nasopharyngeal carcinoma using tissue microarray analysis.
AB  - Studies have revealed that Epstein-Barr virus (EBV) infection, genetic
      aberration, and environmental factors are of importance in the development of
      nasopharyngeal carcinoma (NPC), although the definite mechanism remains to be
      fully elucidated. The aim of our study is to investigate using tissue microarray
      analysis whether differential expression of EBV-encoded small RNA-1 (EBER-1) and
      several tumor-related genes were associated with NPC carcinogenesis.
      Immunohistochemistry and in situ hybridization were performed on tissue
      microarrays containing 148 NPCs and 164 noncancerous nasopharyngeal epithelia
      (NPE) with different morphologic features. We found that overexpressions of EBER
      1 hybridization signals, p53, p21ras, and bcl-2 proteins and loss expressions of
      p16 and p27 proteins were significantly increased in NPC tissues compared with
      normal NPE and hyperplastic NPE (P </= .001). The overexpressions of EBER-1 and
      p53 (P < .001) and the loss expressions of P16 (P < .001) and P27 (P = .005) were
      also significantly higher and more frequently observed in NPC than in dysplastic
      NPE. The positive expression of EBER-1 hybridization signals in NPC had
      significant associations with overexpressions of p53 (P < .001), p21ras (P =
      .041), and bcl-2 proteins (P < .001) and loss expression of p16 protein (P =
      .001). Further analysis confirmed that the abnormal expression of p53, p16, and
      p27 proteins occurred in the earliest stage of nasopharyngeal epithelial
      carcinogenesis. In the final logistic regression analysis model, the positive
      hybridization signals of EBER-1 and the abnormal expression of p53, p16, and p27
      proteins were independent contributions for nasopharyngeal carcinogenesis, and
      EBER-1 was the most significant, independent predictor of nasopharyngeal
      carcinogenesis (hazard ratio = 13.412, 95% confidence interval 6.179-29.111, P <
      .001). In conclusion, EBV infection, together with overexpressions of p53, and
      loss expressions of p16 and p27 proteins are involved in the multistep process of
      human nasopharyngeal epithelial carcinogenesis.

PMID- 16647959
TI  - Comparative genomic hybridization study of perivascular epithelioid cell tumor:
      molecular genetic evidence of perivascular epithelioid cell tumor as a
      distinctive neoplasm.
AB  - Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of
      HMB-45-positive epithelioid cells with clear to granular cytoplasm and a
      perivascular distribution. Such tumors have been reported in different organs
      under a variety of designations. The cytogenetic features of these neoplasms have
      not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of
      urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8
      patients, including one patient with tuberous sclerosis complex. The paraffin
      blocks of tumor tissue were submitted for comparative genomic hybridization
      analyses. Gross chromosomal aberrances were observed in all cases. The frequent
      imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases),
      1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6
      cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p
      in which TSC2 gene is located indicates the oncogenetic relationship of PEComas
      with angiomyolipoma as a TSC2-linked neoplasm. From a molecular genetic
      perspective, the recurrent chromosomal alterations in both renal and extrarenal
      tumors further support the concept of PEComa as a distinctive tumor entity
      regardless of anatomic location.

PMID- 16647960
TI  - Differential expression of desmosomal plakophilins in various types of
      carcinomas: correlation with cell type and differentiation.
AB  - Plakophilins (PKPs) are a set of 3 constitutive armadillo repeat proteins of the
      desmosomal plaque, termed PKP 1, PKP 2, and PKP 3, which have been shown to be
      functionally relevant for desmosomal adhesion. We have performed a systematic
      immunohistochemical study of the 3 PKPs in oral and pharyngeal squamous cell
      carcinomas (SqCCs; n = 40); colorectal, pancreatic, and prostate adenocarcinomas
      (n = 31), and hepatocellular carcinomas (HCCs; n = 8). In SqCCs, PKP 1 and PKP 3
      revealed common desmosome-type immunostaining, their expression level being
      inversely correlated with the degree of malignancy. Instead, staining for PKP 2
      was limited. In contrast, all adenocarcinomas contained PKP 2 and-often
      abundantly-PKP 3 in desmosome-typical pattern, whereas PKP 1 was expressed only
      in prostate tumors. The presence of PKP 3 in adenocarcinomas was confirmed by
      immunoblotting. In HCCs, only PKP 2 was detected. Under certain staining
      conditions, focal nuclear immunoreactivity for PKP 1 was observed in some SqCCs
      and HCCs. Our results, which are inconsistent with previously published data to
      some extent, indicate a principal preservation of the cell type and
      differentiation-related expression patterns of PKPs in normal epithelia. For PKP
      1, a suppressor function of malignant behavior seems conceivable, whereas the
      putative functional significance of its occurrence in tumor cell nuclei requires
      further studies.

PMID- 16647961
TI  - Corticotropin-producing pulmonary gangliocytic paraganglioma associated with
      Cushing's syndrome.
AB  - Gangliocytic paraganglioma (GP) is an unusual tumor in the wide spectrum of
      neuroendocrine neoplasms. The biologic behavior and histogenesis of this tumor is
      uncertain because, despite its benign histologic features, there have been
      reports of metastases to regional lymph nodes and distant metastases. Although
      most of these tumors have been reported in the duodenum, examples of GP arising
      in extra-ampullary sites have been well documented. Herein, we report the case of
      a lung GP corticotropin producing and presenting as Cushing's syndrome. After
      removal of the tumor, there was a significant drop in cortisol and corticotropin
      levels. To our knowledge, this is the first report of a GP causing Cushing's
      syndrome.

PMID- 16647962
TI  - Papillary glioneuronal tumor with minigemistocytic components and increased
      proliferative activity.
AB  - Papillary glioneuronal tumor (PGNT) is a rare and new type of glioneuronal
      neoplasm of the central nervous system. It is characterized by pseudopapillary
      structures composed of hyalinized vessels rimmed by cuboidal glial cells and the
      proliferation of neuronal cells. We report a peculiar PGNT arising in the
      parietal lobe of a 67-year-old man, which was characterized by proliferation of
      minigemistocytic cells as well as typical components. The minigemistocytic cells
      had eccentric nuclei and plump eosinophilic cytoplasm that was filled with glial
      filaments. The Ki-67 labeling index was as high as 10% in the minigemistocytic
      areas. Recently, the presence of oligodendroglial-like component was suggested in
      PGNT. Considering that oligodendroglioma sometimes accompanies minigemistocytic
      components, the minigemistocytic cells in PGNT were suggested to be a part of
      oligodendroglial differentiation. Although PGNT is defined as an indolent
      glioneuronal tumor, the presence of minigemistocytic components with the high Ki
      67 labeling index may indicate more aggressive nature.

PMID- 16647963
TI  - Small bowel adenocarcinoma with high levels of microsatellite instability in
      Crohn's disease.
AB  - Microsatellite instability (MSI) is a hallmark of carcinomas occurring in the
      setting of hereditary nonpolyposis colorectal cancer, but can also be found in
      sporadic and colitis-associated tumors. The incidence of MSI in Crohn's disease
      is unknown and has usually been reported in the colon. We report the case of a 26
      year-old man, diagnosed 4 years earlier with Crohn's disease, who developed an
      associated small bowel adenocarcinoma. The tumor was found to have high levels of
      MSI by immunohistochemical staining and by MSI testing. No mutations were
      identified by genetic testing, and high levels of MSI are most probably due to
      hypermethylation.

PMID- 16647964
TI  - Guest editors' preface. Global mapping of infectious diseases: methods, examples
      and emerging applications.

PMID- 16647966
TI  - Models for vectors and vector-borne diseases.
AB  - The development of models for species' distributions is briefly reviewed,
      concentrating on logistic regression and discriminant analytical methods.
      Improvements in each type of modelling approach have led to increasingly accurate
      model predictions. This review addresses several key issues that now confront
      those wishing to choose the "right" sort of model for their own application. One
      major issue is the number of predictor variables to retain in the final model.
      Another is the problem of sparse datasets, or of data reported to administrative
      levels only, not to points. A third is the incorporation of spatial co-variance
      and auto-covariance in the modelling process. It is suggested that many of these
      problems can be resolved by adopting an information-theoretic approach whereby a
      group of reasonable potential models is specified in advance, and the "best"
      candidate model is selected among them. This approach of model selection and
      multi-model inference, using various derivatives of the Kullback-Leibler
      information or distance statistic, puts the biologist, with her or his insight,
      back in charge of the modelling process that is usually the domain of
      statisticians. Models are penalized when they contain too many variables; careful
      specification of the right set of candidate models may also be used to identify
      the importance of each predictor variable individually; and finally the degree to
      which the current "best" model improves on all the other models in the candidate
      set may be quantified. The ability definitely to exclude some models from the
      realm of all possible models appropriate for any particular distribution problem
      may be as important as the ability to identify the best current model.

PMID- 16647967
TI  - Global environmental data for mapping infectious disease distribution.
AB  - This contribution documents the satellite data archives, data processing methods
      and temporal Fourier analysis (TFA) techniques used to create the remotely sensed
      datasets on the DVD distributed with this volume. The aim is to provide a
      detailed reference guide to the genesis of the data, rather than a standard
      review. These remotely sensed data cover the entire globe at either 1 x 1 or 8 x
      8 km spatial resolution. We briefly evaluate the relationships between the 1 x 1
      and 8 x 8 km global TFA products to explore their inter-compatibility. The 8 x 8
      km TFA surfaces are used in the mapping procedures detailed in the subsequent
      disease mapping reviews, since the 1 x 1 km products have been validated less
      widely. Details are also provided on additional, current and planned sensors that
      should be able to provide continuity with these environmental variable surfaces,
      as well as other sources of global data that may be used for mapping infectious
      disease.

PMID- 16647968
TI  - Issues of scale and uncertainty in the global remote sensing of disease.
AB  - Scale and uncertainty are important issues for the global prediction of disease.
      Disease mapping over the entire surface of the Earth usually involves the use of
      remotely sensed imagery to provide environmental covariates of disease risk or
      disease vector density. It further implies that the spatial resolution of such
      imagery is relatively coarse (e.g., 8 or 1km). Use of a coarse spatial resolution
      limits the information that can be extracted from imagery and has important
      effects on the results of epidemiological analyses. This paper discusses
      geostatistical models for (i) characterizing the scale(s) of spatial variation in
      data and (ii) changing the scale of measurement of both the data and the
      geostatistical model. Uncertainty is introduced, highlighting the fact that most
      epidemiologists are interested in accuracy, aspects of which can be estimated
      with measurable quantities. This paper emphasizes the distinction between data-
      and model-based methods of accuracy assessment and gives examples of both. The
      key problem of validating global maps is considered.

PMID- 16647969
TI  - Determining global population distribution: methods, applications and data.
AB  - Evaluating the total numbers of people at risk from infectious disease in the
      world requires not just tabular population data, but data that are spatially
      explicit and global in extent at a moderate resolution. This review describes the
      basic methods for constructing estimates of global population distribution with
      attention to recent advances in improving both spatial and temporal resolution.
      To evaluate the optimal resolution for the study of disease, the native
      resolution of the data inputs as well as that of the resulting outputs are
      discussed. Assumptions used to produce different population data sets are also
      described, with their implications for the study of infectious disease. Lastly,
      the application of these population data sets in studies to assess disease
      distribution and health impacts is reviewed. The data described in this review
      are distributed in the accompanying DVD.

PMID- 16647970
TI  - Defining the global spatial limits of malaria transmission in 2005.
AB  - There is no accurate contemporary global map of the distribution of malaria. We
      show how guidelines formulated to advise travellers on appropriate
      chemoprophylaxis for areas of reported Plasmodium falciparum and Plasmodium vivax
      malaria risk can be used to generate crude spatial limits. We first review and
      amalgamate information on these guidelines to define malaria risk at national and
      sub-national administrative boundary levels globally. We then adopt an iterative
      approach to reduce these extents by applying a series of biological limits
      imposed by altitude, climate and population density to malaria transmission,
      specific to the local dominant vector species. Global areas of, and population at
      risk from, P. falciparum and often-neglected P. vivax malaria are presented for
      2005 for all malaria endemic countries. These results reveal that more than 3
      billion people were at risk of malaria in 2005.

PMID- 16647971
TI  - The global distribution of yellow fever and dengue.
AB  - Yellow fever has been subjected to partial control for decades, but there are
      signs that case numbers are now increasing globally, with the risk of local
      epidemic outbreaks. Dengue case numbers have also increased dramatically during
      the past 40 years and different serotypes have invaded new geographical areas.
      Despite the temporal changes in these closely related diseases, and their
      enormous public health impact, few attempts have been made to collect a
      comprehensive dataset of their spatial and temporal distributions. For this
      review, records of the occurrence of both diseases during the 20th century have
      been collected together and are used to define their climatic limits using
      remotely sensed satellite data within a discriminant analytical model framework.
      The resulting risk maps for these two diseases identify their different
      environmental requirements, and throw some light on their potential for co
      occurrence in Africa and South East Asia.

PMID- 16647972
TI  - Global epidemiology, ecology and control of soil-transmitted helminth infections.
AB  - Soil-transmitted helminth (STH) infections are among the most prevalent of
      chronic human infections worldwide. Based on the demonstrable impact on child
      development, there is a global commitment to finance and implement control
      strategies with a focus on school-based chemotherapy programmes. The major
      obstacle to the implementation of cost-effective control is the lack of accurate
      descriptions of the geographical distribution of infection. In recent years,
      considerable progress has been made in the use of geographical information
      systems (GIS) and remote sensing (RS) to better understand helminth ecology and
      epidemiology, and to develop low-cost ways to identify target populations for
      treatment. This review explores how this information has been used practically to
      guide large-scale control programmes. The use of satellite-derived environmental
      data has yielded new insights into the ecology of infection at a geographical
      scale that has proven impossible to address using more traditional approaches,
      and has in turn allowed spatial distributions of infection prevalence to be
      predicted robustly by statistical approaches. GIS/RS have increasingly been used
      in the context of large-scale helminth control programmes, including not only STH
      infections but also those focusing on schistosomiasis, filariasis and
      onchocerciasis. The experience indicates that GIS/RS provides a cost-effective
      approach to designing and monitoring programmes at realistic scales. Importantly,
      the use of this approach has begun to transition from being a specialist approach
      of international vertical programmes to becoming a routine tool in developing
      public sector control programmes. GIS/RS is used here to describe the global
      distribution of STH infections and to estimate the number of infections in school
      age children in sub-Saharan Africa (89.9 million) and the annual cost of
      providing a single anthelmintic treatment using a school-based approach (US$5.0
      7.6 million). These are the first estimates at a continental scale to explicitly
      include the fine spatial distribution of infection prevalence and population, and
      suggest that traditional methods have overestimated the situation. The results
      suggest that continent-wide control of parasites is, from a financial
      perspective, an attainable goal.

PMID- 16647973
TI  - Tick-borne disease systems: mapping geographic and phylogenetic space.
AB  - Evidence is presented that the evolution of the tick-borne flaviviruses is driven
      by biotic factors, principally the exploitation of new hosts as transmission
      routes. Because vector-borne diseases are limited by climatic conditions,
      however, abiotic factors have the potential to direct and constrain the
      evolutionary pathways. This idea is explored by testing the hypothesis that
      closely related viruses occupy more similar eco-climatic spaces than do more
      distantly related viruses. A statistical comparison of the conventional
      phylogenetic tree derived from molecular distances and a novel phenetic tree
      derived from distances between the climatic spaces within which each virus
      circulates, indicates that these trees match each other more closely than would
      be expected at random. This suggests that these viruses are indeed limited in the
      degree to which they can evolve into new environmental conditions.

PMID- 16647975
TI  - Climate change and vector-borne diseases.
AB  - In this review we examine formally the conditions under which vector-borne
      diseases are likely to change, and the directions of those changes, under various
      scenarios of climate change. We specify the criteria that must be met in order to
      conclude that climate change is having an effect on vector-borne diseases. We
      then take several examples from the literature and show how some of them meet
      these criteria, while others do not. For those that do not, there are alternative
      explanations that involve much more plausible drivers of the recorded changes in
      the diseases concerned.

PMID- 16647974
TI  - Global transport networks and infectious disease spread.
AB  - Air, sea and land transport networks continue to expand in reach, speed of travel
      and volume of passengers and goods carried. Pathogens and their vectors can now
      move further, faster and in greater numbers than ever before. Three important
      consequences of global transport network expansion are infectious disease
      pandemics, vector invasion events and vector-borne pathogen importation. This
      review briefly examines some of the important historical examples of these
      disease and vector movements, such as the global influenza pandemics, the
      devastating Anopheles gambiae invasion of Brazil and the recent increases in
      imported Plasmodium falciparum malaria cases. We then outline potential
      approaches for future studies of disease movement, focussing on vector invasion
      and vector-borne disease importation. Such approaches allow us to explore the
      potential implications of international air travel, shipping routes and other
      methods of transport on global pathogen and vector traffic.

PMID- 16647977
TI  - Pulmonary arterial pressure in children with croup syndrome.
AB  - PURPOSE: Croup syndrome or laryngotracheitis is one of the frequent causes of
      transient upper airway obstruction by laryngeal and tracheal blockage in infants
      and children. Upper airway obstruction may lead to increased pulmonary arterial
      pressure in children. In this study, the relationship between croup syndrome and
      pulmonary arterial pressure was investigated. MATERIALS AND METHODS: Forty
      children with croup syndrome and 14 healthy, age- and sex-matched control
      subjects were enrolled in this study. Of all patients, 12 with severe symptoms,
      such as dyspnea, cyanosis, hypoventilation, were accepted as "high croup score"
      (croup score >or=6). All patients with high croup score were treated with
      dexamethasone. We assessed pulmonary arterial pressure of patients during therapy
      using serial echocardiographic measurements. RESULTS: Our results showed that
      children with croup syndrome have significantly higher pulmonary arterial
      pressures than healthy subjects at the time of diagnosis. Pressure values of
      patients with high croup score were found to be significantly higher when
      compared with those of the low -core group (P < .05). However, there was no
      difference between 2 groups at the end of therapy. CONCLUSIONS: It is suggested
      that pulmonary arterial pressure increased to different extents in the acute
      stage of illness and that the degree of increase was related to the severity of
      disease and average hospital stay. In addition, increased pulmonary arterial
      pressure due to croup syndrome is reversible. Furthermore, evaluation of children
      with croup syndrome by using Doppler echocardiography may be useful in the
      monitoring of pulmonary arterial pressure and in the follow-up of their therapy.

PMID- 16647978
TI  - Long-term asthma outcomes after endoscopic sinus surgery in aspirin triad
      patients.
AB  - BACKGROUND: Aspirin triad disease (ATD) is a well-known clinical entity
      characterized by asthma, polyposis, and aspirin intolerance. Using subjective and
      objective clinical data, this study examines the short- and long-term outcomes of
      asthma after sinus surgery in patients with ATD. METHODS: A retrospective review
      and standardized survey in the setting of an academic tertiary rhinology program.
      Eighty-five patients with ATD who had endoscopic sinus surgery between 1986 and
      1998 were identified from an internal database. Standardized surveys were sent to
      each patient to assess both objective and subjective improvement of their asthma.
      RESULTS: The address and location of 20 of 85 patients could not be ascertained.
      Thirty-four of the remaining 65 patients (52.3%) with ATD who underwent
      endoscopic sinus surgery responded to the survey. Respondents had a mean follow
      up of 10 years. Overall, 29 (94%) of 31 patients who reported asthma symptoms
      preoperatively noted long-term postoperative improvement. Furthermore, 21 of
      these 31 patients (68%) reported further improvement of their asthma beyond the
      first postoperative year. Emergency department visits for asthma exacerbations
      decreased in 17 (94%) of 18. Inpatient hospitalizations for asthma exacerbations
      also decreased in the first postoperative year in 10 (91%) of 11 patients. Asthma
      attacks declined in 12 (41%) of 27 patients the first year, whereas 24 (88.9%) of
      27 patients had fewer asthma attacks in the last 12 months of follow-up. Peak
      flow rates improved from an average of 60% of the predicted value preoperatively
      to 86% at the time of follow-up. CONCLUSIONS: The asthma component of ATD
      continues to improve with time after endoscopic sinus surgery. Although the most
      dramatic decrease occurs in the first year after sinus surgery, the majority of
      patients noted further improvement in subsequent years.

PMID- 16647979
TI  - Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant
      Staphylococcus aureus with mupirocin irrigations.
AB  - INTRODUCTION: Chronic rhinosinusitis (CRS) exacerbations due to methicillin
      resistant Staphylococcus aureus (MRSA) are routinely encountered. Treatment often
      involves intravenous antibiotics that provide only transient benefits. Mupirocin
      has well-recognized antistaphylococcal activity, and its nasal formulation is
      approved by the Food and Drug Administration for the eradication of nasal
      colonization with MRSA. OBJECTIVE: The aim of this study was to describe the use
      of mupirocin nasal irrigations for the treatment of CRS exacerbations due to
      MRSA. MATERIALS AND METHODS: Charts of patients who received mupirocin nasal
      irrigations for MRSA exacerbations of CRS between January 2000 and October 2003
      were reviewed. RESULTS: Forty-two MRSA-positive cultures were obtained from 24
      patients (mean age, 61 years; range, 38-82 years; 15 women and 6 men). Twenty
      eight episodes were treated with mupirocin nasal irrigations and doxycycline; 4
      were treated with mupirocin nasal irrigations and trimethoprim-sulfamethoxazole,
      and 7 episodes were treated with mupirocin nasal irrigations alone. Patients were
      reevaluated at approximately 4 to 6 weeks. Repeat cultures were not obtained in
      12 patients (because of clinical and endoscopic resolution). Adequate follow-up
      was unavailable for 3 patients, and of the 27 repeat cultures, only 1 grew MRSA.
      Twelve patients had at least one recurrence, with a mean number of episodes of
      1.75 (range, 1-8 episodes). The mean follow-up was 11.8 months (range, 3-27
      months). CONCLUSIONS: Mupirocin nasal irrigations may avoid the need for
      intravenous antibiotics, which often provide temporary benefits and entail
      greater cost and morbidity. Thus, mupirocin nasal irrigations may provide a
      relatively simple means for the management of MRSA exacerbations of CRS.

PMID- 16647980
TI  - Cochlear nerve size evaluation in children with sensorineural hearing loss by
      high-resolution magnetic resonance imaging.
AB  - PURPOSE: To determine differences in size of cochlear nerves among subjects with
      deafness due to connexin 26 (Cx26) mutations, subjects with deafness of unknown
      origin, and normal hearing subjects by sagittal high-resolution magnetic
      resonance (HRMR) imaging of the temporal bone. MATERIALS AND METHODS: Cross
      sectional and surface areas and volumetric measurements of the cochlear nerve and
      modiolus were made on HRMR images of the internal auditory canal (IAC) and inner
      ear in the 3 groups of children (groups 1, 2, and 3). Three-way comparisons of in
      vivo cochlear nerve measurements on HRMR imaging were made among 17 children with
      sensorineural hearing loss (SNHL) and no obvious etiology for the hearing loss
      (group 1), 7 children with profound SNHL due to a Cx26 mutation (group 2), and 10
      normal hearing children (group 3). RESULTS: Children with profound SNHL of
      unknown cause and children with profound SNHL due to a connexin mutation
      displayed hypoplastic cochlear nerves as compared with normal controls. HRMR
      imaging of the temporal bone was accurately delineated potential problems with
      cochlear nerves in 2 of 17 instances where high-resolution computed tomography
      did not do so. CONCLUSIONS: Accurate and specific measurements of the cochlear
      nerve and related structures is possible on HRMR imaging of the temporal bone.
      The size of the cochlear nerve is mildly hypoplastic in children with profound
      SNHL of unknown causes or children with a deafness-causing Cx26 mutation. HRMR
      imaging is superior to high-resolution computed tomography in the investigation
      of profound SNHL in children.

PMID- 16647981
TI  - Anterior semicircular canal benign paroxysmal positional vertigo and positional
      downbeating nystagmus.
AB  - PURPOSE: The aim of this study was to describe the clinical features and video
      oculographic findings in patients with anterior semicircular canal benign
      paroxysmal positional vertigo (BPPV). MATERIALS AND METHODS:  STUDY DESIGN: This
      is a prospective case series. SETTING: The study was set at an outpatient clinic
      in a general hospital. PATIENTS: Fourteen individuals with symptoms of BPPV and
      positional downbeating nystagmus (pDBN) were included in the study. The diagnosis
      was based on a history of brief episodes of vertigo and the presence of pDBN
      confirmed in the video-oculographic examination during Dix-Hallpike test (DH) or
      head-hanging maneuver. INTERVENTION: Patients were treated by particle
      repositioning maneuver and the effectiveness was evaluated at 7, 30, and 180 days
      posttreatment. The treatment was repeated up to 4 times if pDBN was persistent.
      MAIN OUTCOME MEASURES: The main outcome measure is the number of patients without
      pDBN at 30 and 180 days. RESULTS: Video-oculography showed a predominant pDBN in
      response to DH. Of the 14 patients, 7 had arterial hypertension, and 5 of 14
      cases presented abnormalities on the caloric test. Horizontal spontaneous
      nystagmus was found in 3 of 14 individuals. Positional nystagmus at different
      positional test was observed in 5 of 14 individuals, suggesting the involvement
      of several canals. Of the 14 patients, 10 (71%) did not present vertigo, and the
      positional tests were negative at 30 days. However, 3 cases presented a positive
      DH with persistence of BPPV episodes and pDBN at 30 days, and another developed a
      contralateral posterior canal affectation. One of the patients maintained a
      persistent pDBN at 180 days despite the repeated maneuvers. CONCLUSIONS: Video
      oculography demonstrates that anterior canal BPPV is characterized by a
      predominant downbeating nystagmus in response to DH. These individuals may show
      alterations in the vestibular caloric, and they can have multicanal affectation.

PMID- 16647982
TI  - HIV manifestations in otolaryngology.
AB  - PURPOSE: AIDS is a fatal illness, which breaks down the body's immunity and
      leaves the victim vulnerable to life-threatening opportunistic infections,
      neurological disorders, or unusual malignancies. About 80% of patients with HIV
      infections present with otolaryngological symptoms. Often, the otolaryngologist
      is the primary physician who diagnoses the HIV infection. He should be aware and
      vigilant for its symptoms and unusual presentations. The aim of our study was to
      determine the incidence of otolaryngological manifestations, the clinical
      presentations, relevant diagnostic tools, management, and survival rates.
      MATERIALS AND METHODS: We studied 968 patients who were diagnosed to have HIV
      infection at Kasturba Medical College, Mangalore, India, from January 1996 to
      December 2004. The incidence of otolaryngological manifestations was noted.
      Patients with opportunistic infections were treated by specific and symptomatic
      measures. Of 968 patients studied, 419 were followed up for a 5-year period.
      RESULTS: In our study, otolaryngological findings were noted in 79% of
      individuals. Oropharyngeal findings, which were the commonest, were seen in 59%,
      followed by cervical lymphadenopathy in 42% of patients. Oral candidiasis was the
      commonest oropharyngeal finding, seen in 39% of patients. Among nasal complaints,
      rhinosinusitis was the commonest, found in 17% of patients. Otological
      manifestations were seen in 20%, of which chronic suppurative otitis media was
      the commonest, seen in 13% of patients. Routine investigations were found to
      suffice for diagnosis. Of 419 patients who were followed up, the 5-year survival
      rate was 73%. CONCLUSION: With the increase in the number of AIDS cases, it is
      important for otolaryngologists to be aware of otolaryngological manifestations.
      Early diagnosis and timely intervention along with appropriate antiretroviral
      therapy improve survival rates.

PMID- 16647983
TI  - Prevalence of pH-documented laryngopharyngeal reflux in Chinese patients with
      clinically suspected reflux laryngitis.
AB  - PURPOSE: Laryngopharyngeal reflux (LPR) is one of the main factors behind
      different laryngeal pathology according to the Western literature. Literature
      reported that the prevalence of gastroesophageal reflux disease (GERD) in Chinese
      population was considerably lower than that in Western countries. To date,
      however, there is no study to evaluate the prevalence of pH-documented LPR in the
      Chinese ethnicity. MATERIALS AND METHODS: We thus recruited 28 consecutive
      Chinese patients with reflux symptoms including globus, throat discomfort, throat
      clearing, chronic cough, or burping lasting more than 1 month in the preceding 1
      year, together with stroboscopic evidence suggestive of reflux laryngitis
      according to the reflux finding score in our study. All patients underwent
      thorough head and neck examination and transnasal endoscopic assessment. The
      prevalence of pH-documented LPR and GERD was then documented using ambulatory 24
      hour pH biprobe study. RESULTS: Six (21%) of the 28 patients had pH-documented
      LPR. Four (14%) of the 28 patients had GERD with 3 of them having concomitant
      LPR. Only burping was associated with pH-documented LPR (P < .05). No
      relationship was observed between pH-documented LPR and other factors, including
      age, sex, other reflux symptoms except burping, and the reflux finding score.
      CONCLUSION: Chinese patients do have and present with symptoms of extraesophageal
      reflux, and we observed a lower prevalence of pH-documented LPR in Chinese
      patients with clinically suspected reflux laryngitis compared with white
      patients.

PMID- 16647984
TI  - Factors contributing to nasal allergic late phase eosinophilia.
AB  - OBJECTIVE: This study focused on factors contributing to eosinophilia after
      intranasal allergen challenge. METHODS: Nasal secretions of 13 allergic
      individuals were gained over a period of 8 hours after nasal allergen challenge.
      Early and late phase reactions were determined by acoustic rhinometry and changes
      of volume and total protein in nasal secretions. Eosinophilia was demonstrated by
      nasal eosinophilic cationic protein. Interleukin (IL)-5; the chemokines IL-8,
      monocyte chemotactic protein (MCP)-1 and MCP-3, and eotaxin; soluble vascular
      cell adhesion molecule 1 (sVCAM-1); and the leukotriene C4 (LTC4) were analyzed
      by enzyme-linked immunosorbent assay for their suggested impacts on tissue
      eosinophilia. RESULTS: By means of rhinometry, we observed in 69% an alternating
      type of late phase response, followed by a bilateral (15%) or unilateral (8%)
      type. A biphasic kinetic could be demonstrated by changes in nasal volume and
      total protein of nasal secretions, reflecting the early and late phase responses.
      A typical late phase kinetic was observed for IL-5, MCP-1, eotaxin, sVCAM-1, and
      LTC4. Interleukin 8 was characteristic for early phase reaction but increased in
      late phase as well. We could not detect any MCP-3 in our samples. CONCLUSIONS:
      Our data point to a relevant role of the T(H)2 cytokine IL-5; of the chemokines
      IL-8, MCP-1, and eotaxin; of the adhesion molecule sVCAM-1; and of the
      leukotriene LTC4 for the allergic late phase eosinophilia.

PMID- 16647985
TI  - Laryngeal manifestations and pediatric laryngopharyngeal reflux.
AB  - Pediatric laryngopharyngeal reflux (PLPR) refers to the atypical,
      otorhinolaryngological, and respiratory manifestations of gastroesophageal reflux
      disease in children. PLPR is believed to be an important inflammatory cofactor in
      disorders such as subglottic stenosis, asthma, recurrent croup, chronic
      rhinosinusitis, and middle ear infections. We review the literature, present
      clinical manifestations, and focus on diagnostic controversies and therapeutic
      challenges of PLPR in relation to laryngeal manifestations. Current evidence
      linking reflux to many laryngeal problems is mainly based on animal studies or
      uncontrolled human studies. Future efforts should concentrate on developing well
      designed controlled studies to provide more information on diagnosis and
      treatment.

PMID- 16647986
TI  - Concurrent nonfunctioning parathyroid carcinoma and parathyroid adenoma.
AB  - Parathyroid carcinoma is a rare etiology of primary hyperparathyroidism
      characterized by severe clinical symptoms of hypercalcemia and markedly elevated
      serum parathormone levels. Nonfunctioning parathyroid carcinoma is an inactive
      form of the disease. There are less than 30 reports of nonfunctioning parathyroid
      carcinoma in the English literature and the association with parathyroid adenoma
      has not been described. This report describes a patient with concurrent
      nonfunctioning parathyroid carcinoma and a functioning parathyroid adenoma.

PMID- 16647987
TI  - Follicular dendritic cell sarcoma of the tonsil: a case report.
AB  - Follicular dendritic cell sarcomas of the tonsil are very rare tumors. Only 10
      cases have been published in the English-language medical literature. We present
      an additional case that occurred in a 27-year-old woman. She presented with a
      tumor of the right tonsil. Histological sections of tonsillar biopsies and
      tonsillectomy suggested that this tumor was a nerve sheath tumor or a malignant
      melanoma. Histological examination and immunohistochemical study were reviewed.
      The final diagnosis was follicular dendritic cell sarcoma. She underwent a
      transoral resection of the right oropharynx with ipsilateral selective neck
      dissection and postoperative irradiation. We emphasize the difficulties in
      diagnosing this type of tumor. The use of monoclonal specific markers is required
      to avoid misdiagnosis. We discuss therapeutic methods for this rare tumor for
      which optimal treatment has not yet been defined.

PMID- 16647988
TI  - Para-alar crescentic subcutaneous pedicle flap for severe stenosis of anterior
      nares.
AB  - Atresia and stenosis of the anterior nares caused by scar contracture is one of
      the intractable conditions that may arise after facial injury. Using the standard
      surgical methods, such as mucous membrane and/or skin graft and intranasal local
      flap, the new nostril has a tendency to restenose. Para-alar crescentic
      subcutaneous pedicle flap, which was intended to cover the skin defects in and
      around the philtrum, was applied to treat severe stenosis of the nostril caused
      by scar contracture. The procedure resulted in improvement of nasal obstruction
      with satisfactory postoperative appearance of the external nose. This article
      presents an operative technique using this flap for severe stenosis of anterior
      nares.

PMID- 16647989
TI  - Solitary metastasis of lung carcinoma to the internal auditory canal.
AB  - We report a case of solitary metastasis of lung carcinoma into the internal
      auditory canal. On admission, the 60-year-old patient was complaining about a
      rapidly developing hearing loss with ipsilateral facial nerve paralysis. Magnetic
      resonance imaging revealed an intracanalicular tumor, which was interpreted as
      vestibular schwannoma. After tumor resection, the histopathologic examination
      revealed a metastasis of a squamous cell carcinoma. Computed tomographic scan and
      bronchoscopy identified an asymptomatic primary pulmonary neoplasm.

PMID- 16647990
TI  - Primary nasal non-Hodgkin lymphomas presented initially as benign disease.
AB  - BACKGROUND: Primary non-Hodgkin lymphomas (NHLs) of the sinonasal tract comprise
      a rare entity that constitutes 1.5% of all NHLs and 2.2% of extranodal lymphomas
      in the whites. Clinical diagnosis may be very challenging because of the variety
      and low specificity of the presenting symptoms and signs. METHODS-RESULTS: We
      present three cases of NHLs, initially diagnosed as benign diseases. All three
      cases have been eventually correctly diagnosed and treated in our hospital
      between January 2000 and December 2003. The patients have been under close follow
      up from 11 to 36 months after the initial treatment. One of them remains without
      clinical or radiological evidence of recurrence, whereas the two others died 11
      and 16 months after the initial diagnosis. CONCLUSION: It is important to
      underline that atypical or persistent symptoms of rhinosinusitis may represent
      the initial expression of a more serious condition such as deep fungal infection,
      vasculitis, lymphoma, or other malignancy.

PMID- 16647991
TI  - The role of botulinum toxin in postparotidectomy fistula treatment. A technical
      note.
AB  - PURPOSE: Parotid fistula is a well-known complication of parotidectomy or
      penetrating injury of the parotid gland. The management of parotid fistula has
      been controversial, and numerous conservative and surgical treatment methods have
      been described. METHODS: We report 3 cases of parotid fistula after partial
      parotidectomy, which were treated by botulinum toxin injection under
      electromyographic control into the residual substance of parotid gland. RESULTS:
      Complete healing of the fistula was achieved with a single botulinum toxin
      treatment in all patients. No side effects were observed after the treatment. The
      patients are disease-free after 21, 18, and 14 months, respectively. CONCLUSIONS:
      In the considered cases, the localized injection of botulinum toxin into the
      parotid gland resulted to an effective and long-lasting treatment of
      postparotidectomy fistula.

PMID- 16647992
TI  - Neurologic and developmental features of the Smith-Magenis syndrome (del
      17p11.2).
AB  - The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring,
      mental retardation and multiple congenital anomalies caused by a heterozygous
      interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis
      syndrome is characterized by a distinct pattern of features including infantile
      hypotonia, generalized complacency and lethargy in infancy, minor skeletal
      (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities,
      middle ear and laryngeal abnormalities including hoarse voice, as well as marked
      early expressive speech and language delays, psychomotor and growth retardation,
      and a 24-hour sleep disturbance. A striking neurobehavioral pattern of
      stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive
      and self-injurious and aggressive behavior is observed with increasing age. The
      diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a
      constellation of physical, developmental, and behavioral features in combination
      with a sleep disorder characterized by inverted circadian rhythm of melatonin
      secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy
      and early childhood, and become more recognizable with advancing age. Infants are
      described as looking "cherubic" with a Down syndrome-like appearance, whereas
      with age the facial appearance is that of relative prognathism. Early diagnosis
      requires awareness of the often subtle clinical and neurobehavioral phenotype of
      the infant period. Speech delay with or without hearing loss is common. Most
      children are diagnosed in mid-childhood when the features of the disorder are
      most recognizable and striking. While improvements in cytogenetic analysis help
      to bring cases to clinical recognition at an earlier age, this review seeks to
      increase clinical awareness about Smith-Magenis syndrome by presenting the
      salient features observed at different ages including descriptions of the
      neurologic and behavioral features. Detailed review of the circadian rhythm
      disturbance unique to Smith-Magenis syndrome is presented. Suggestions for
      management of the behavioral and sleep difficulties are discussed in the context
      of the authors' personal experience in the setting of an ongoing Smith-Magenis
      syndrome natural history study.

PMID- 16647993
TI  - Efficacy and safety of zonisamide monotherapy in a cohort of children with
      epilepsy.
AB  - The aim of this study was to evaluate the efficacy and safety of zonisamide
      monotherapy in a cohort of children and adolescents with various types of
      epilepsy. Retrospective review of charts of our institution from 2001 through
      2004 identified 69 children (19 males and 50 females, mean age 13.2 years) with
      epilepsy on zonisamide monotherapy. Seizure count and side effect profile were
      maintained during therapy. Sixty-one percent had idiopathic generalized epilepsy,
      4% symptomatic generalized epilepsy, and 35% partial-onset epilepsy. Zonisamide
      was the first-line and second-line monotherapy for 32% and 68% of patients,
      respectively. The mean duration of follow-up on treatment was 22 months (range 3
      48 months). The overall efficacy of zonisamide was 75.4% (> or = 50% seizure
      frequency reduction: good responders). Sixty-seven percent of good responders
      became seizure-free. Seventy-nine percent of patients with partial epilepsy and
      71% with generalized epilepsy were good responders, of whom 79% and 63% were free
      of seizure, respectively. Eighteen (26%) patients developed side effects: weight
      loss (9), cognitive impairment (3), sleepiness (3), dizziness (2), and decreased
      appetite (1). In seven patients (10%), zonisamide had to be discontinued: four
      due to side effects and three because of poor seizure control. Zonisamide was
      demonstrated to be effective as monotherapy in children with epilepsy.

PMID- 16647994
TI  - Intranasal midazolam vs rectal diazepam in acute childhood seizures.
AB  - One hundred eighty-eight seizure episodes in 46 children were randomly assigned
      to receive treatment with rectal diazepam and intranasal midazolam with doses of
      0.3 mg/kg body weight and 0.2 mg/kg body weight, respectively. Efficacy of the
      drugs was assessed by drug administration time and seizure cessation time. Heart
      rate, blood pressure, respiratory rate, and oxygen saturation were measured
      before and after 5, 10, and 30 minutes following administration of the drugs in
      both groups. Mean time from arrival of doctor to drug administration was 68.3 +/-
      55.12 seconds in the diazepam group and 50.6 +/- 14.1 seconds in the midazolam
      group (P = 0.002). Mean time from drug administration to cessation of seizure was
      significantly less in the midazolam group than the diazepam group (P = 0.005).
      Mean heart rate and blood pressure did not vary significantly between the two
      drug groups. However, mean respiratory rate and oxygen saturation differed
      significantly between the two drug groups at 5, 10, and 30 minutes after drug
      administration. Intranasal midazolam is preferable to rectal diazepam in the
      treatment of acute seizures in children. Its administration is easy, it has rapid
      onset of action, has no significant effect on respiration and oxygen saturation,
      and is socially acceptable.

PMID- 16647995
TI  - Prognostic value of 1H-MRS in neonatal encephalopathy.
AB  - The aim of this study was to determine the prognostic value of proton magnetic
      resonance spectroscopy in neonatal encephalopathy. Studies were carried out in 11
      consecutive term newborns with encephalopathy probably caused by hypoxic-ischemic
      injury. The clinical evaluation included pregnancy data, labor conditions,
      encephalopathy grade, presence of seizures, and necessity of antiepileptic drug
      therapy. Polygraphic recordings were obtained in all cases. Interest areas
      evaluated by spectroscopy were the basal ganglia and thalami. Among the cases, N
      acetylaspartate/creatine, choline/creatine, and lactate/creatine ratios were
      calculated and related to the clinical variables, polygraphic recordings, and 6
      month neurodevelopmental outcome. Abnormal follow-up occurred in 5 of 11 patients
      (45.4%) and was clearly related to an Apgar score <5 at 5 minutes (P = 0.003),
      encephalopathy grade (P = 0.02), early neonatal seizures (P = 0.02), and
      antiepileptic therapy (P = 0.01). No relationship was observed between
      spectroscopy results and polygraphic recordings profile. The lowest mean N
      acetylaspartate/creatine ratio was observed in four of five patients with an
      adverse outcome and, although not statistically significant, demonstrated a clear
      trend to unfavorable follow-up (t test = 0.06). The choline/creatine ratios could
      not be related to follow-up in our sample. The most consistently observed
      abnormality on the spectra was the presence of the lactate peak in four of five
      patients with unfavorable outcome, with a high relative risk to determine
      evolution in the sample, relative risk 7.0 (chi2 = 0.01, 95% confidence interval
      = 1.1-42.9).

PMID- 16647996
TI  - Level of tau protein in children treated for acute lymphoblastic leukemia.
AB  - Long-term neuropsychological complications such as attention and concentration
      disturbances, poor school performance, hyperexcitability, and even
      leukoencephalopathy have been described in children after chemotherapy for acute
      lymphoblastic leukemia. Elevation of the cerebrospinal fluid level of tau
      protein, associated with neuronal axons, is a neurodegenerative marker. The aim
      of the study was to assess the level of cerebrospinal fluid tau protein in
      children with acute lymphoblastic leukemia. The study included 26 patients with
      acute lymphoblastic leukemia and 19 patients with clinical symptoms of
      cerebrospinal meningitis (reference group). Tau protein levels were determined by
      enzyme-linked immunosorbent assay. Cerebrospinal fluid total protein level was
      not elevated in any of the samples. The examination was performed at diagnosis,
      after induction treatment, during consolidation, and after reinduction, i.e.
      before maintenance therapy. Neither age nor sex had an effect on tau protein
      levels in both groups. The mean tau protein value at diagnosis was 244.84 +/-
      98.96 pg/mL in the study group (norm 300 pg/mL) and produced no correlation with
      initial leukocytosis, lactate dehydrogenase activity, or organomegaly at this
      point. Dynamic analysis revealed a statistically significant increase in tau
      protein after induction treatment (431.25 +/- 232.50) as compared with its level
      at diagnosis (244.84 +/- 98.96, P < 0.008) and later during treatment. The levels
      of tau protein at various points of treatment did not differ statistically
      significantly between the groups, except for the values obtained after
      termination of remission induction. The observed metabolic changes in tau
      protein, which is a known marker of neuronal damage, indicate that some patients
      are at a greater risk of central nervous system disorders. This finding requires
      further studies, also in reference to other central nervous system proteins, and
      confirms the necessity of long-term follow-up of leukemia patients.

PMID- 16647997
TI  - The incidence of Rett syndrome in France.
AB  - Since the description of Rett syndrome, only a handful of epidemiologic studies
      based only on clinical investigation have been reported. Mutations in the MECP2
      gene are associated with Rett syndrome and French laboratories have organized a
      clinical and molecular network to investigate the incidence of Rett syndrome in
      France including the results of molecular investigations. The present study,
      based on a large cohort of 424 patients with Rett syndrome, found that the
      incidence of this disease with a MECP2 mutation varied between 0.43 to 0.71 per
      10,000 females. The total population of females aged 4-15 years in November 2004
      in France was estimated to be 4,337,627. The data presented here indicate a
      prevalence of Rett syndrome of 0.558 per 10,000 females aged 4-15 years in
      France. The incidence of Rett syndrome is in accordance with other European
      epidemiologic studies based on clinical examination. Given that this is a minimum
      incidence because complete inventory was not possible, this study of patients
      with Rett syndrome reinforces the fact that the great majority of patients with
      Rett syndrome have a MECP2 mutation.

PMID- 16647998
TI  - Descriptive epidemiology of concussion.
AB  - To describe the epidemiology of reported concussion derived from a large,
      nationally representative health survey, the microdata files of the Canadian
      National Population Health Survey (1996-1997) were analyzed. Respondents reported
      whether they had "any injuries that were serious enough to limit their normal
      activities" in the preceding 12 months and the nature of the most serious injury.
      A total of 99.8% of 81,804 eligible respondents, representing 28,606,100
      Canadians, reported their injury experience within the preceding year, with 89
      reporting a concussion. The annual prevalence of Canadians reporting a concussion
      as their most serious injury was 110 per 100,000 population (95% confidence
      interval: 80, 140). Those reporting concussion were more likely to be younger (P
      < 0.001) and male (P = 0.02). Males were significantly overrepresented in the 16
      34 year-old group (P = 0.004). More than 54% of all concussions were sport
      related (95% confidence interval: 39%, 67%), occurring at a place for recreation
      or sport, with sport having a role in >85% of concussions in the 16-34 year-old
      group. This study presents annual prevalence estimates of reported concussion,
      derived from a sizeable, nationally representative population survey.

PMID- 16647999
TI  - Critical score of Glasgow Coma Scale for pediatric traumatic brain injury.
AB  - The aim of this study is to determine the predictive critical value of the
      Glasgow Coma Scale for use as a determinant of outcome for children with
      traumatic brain injuries. A total of 309 children, aged 2-10 years, were enrolled
      in this study. Each subject underwent the following assessments: Glasgow Coma
      Scale; clinical data; brain computed tomography; and Glasgow Outcome Scale
      assessments. The receiver operating characteristic curve indicated that a
      critical point of the Glasgow Coma Scale set at 5 was most strongly correlated
      with outcome of pediatric traumatic brain injury. Subarachnoid hemorrhage with
      brain swelling and edema, subdural, intracerebral hemorrhage, and basal ganglion
      lesions were associated with severe injury and poor outcome (P < 0.05). However,
      cortical lesions did not affect injury severity and outcome. In injuries
      associated with traumatic brain injuries, only chest trauma had a tendency to be
      associated with poor outcome (P < 0.05). Of the factors analyzed, the score of
      the Glasgow Coma Scale was the most effective predictor for outcome in pediatric
      traumatic brain injury. Furthermore, the predictive critical score of the Glasgow
      Coma Scale should be set at 5 for pediatric traumatic brain injury. The computed
      tomographic findings also were important in determining injury severity and
      predicting outcome.

PMID- 16648000
TI  - Postictal psychosis in a child.
AB  - Postictal psychosis is a state of psychosis following repeated or prolonged
      complex partial seizures with or without secondary generalization and is well
      described in adult epilepsy literature. It is sparsely reported in the pediatric
      literature. This report describes a 12-year-old male presenting with status
      epilepticus who developed psychotic symptoms. Diagnosis of postictal psychosis
      was made after correlating clinical symptoms with video-electroencephalographic
      monitoring. The clinical course of this illness is profiled, and the literature
      reviewed.

PMID- 16648001
TI  - Hypohidrosis during topiramate treatment: a rare and reversible side effect.
AB  - Topiramate is an antiepileptic drug with a beneficial clinical effect on various
      seizure types. Topiramate does not seem to be associated with serious adverse
      effects and is also well tolerated in pediatric patients. Only few cases of
      hypohidrosis have been described. This report presents one young patient with
      complex partial seizures who was medicated with topiramate when she developed
      fatigue, headache, intermittent hyperthermia, inability to produce sweat
      secretion, and dryness of the skin. Reduced sweat response was determined using
      the Wescor Macroduct collection procedure. Topiramate was discontinued, and
      within 3 weeks a repeat sweat test was completely normal. At that time, clinical
      signs had also disappeared. Hypohidrosis is an uncommon and reversible side
      effect reported in association with topiramate therapy. It is rare in patients on
      monotherapy. Although a definite causal relationship still needs to be
      established, this side effect might be attributed to an autonomic dysfunction by
      inhibition of isoenzymes of carbonic anhydrase localized in human eccrine sweat
      glands.

PMID- 16648002
TI  - Group B streptococcal ventriculitis: a report of three cases and literature
      review.
AB  - This report presents three cases of neonatal group B streptococcal ventriculitis
      and assesses seven others identified by a literature review. In contrast to the
      well described acute manifestations of group B streptococcal meningitis, disease
      onset tended to be insidious with four of seven cases presenting over a period of
      1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without
      fever. Persistent protein content elevation and low glucose level in the
      cerebrospinal fluid was observed, indicating chronic inflammation. All patients
      developed obstructive hydrocephalus requiring ventriculoperitoneal shunt
      placement. One child died, and six of nine survivors were left with significant
      neurologic deficits. Physicians should be aware of this indolent but serious
      manifestation of group B streptococcal infection.

PMID- 16648003
TI  - Hemorrhage predisposing to cerebral infarction in children with moyamoya disease.
AB  - Two children with a new diagnosis of hemorrhagic type moyamoya disease
      experienced cerebral infarction after intraventricular hemorrhage. The patients
      developed ischemia 15 and 2 days after the initial diagnosis of hemorrhage. No
      provocative factor such as hypoperfusion was identified, but both patients
      exhibited signs of increased intracranial pressure on computed tomographic scan
      before infarction. Increased intracranial pressure in the setting of hemorrhage
      may be a risk factor for ischemic complications in patients with moyamoya
      disease. The optimal acute management of these patients requires further study.

PMID- 16648004
TI  - The thalamus and midbrain in Reye syndrome.
AB  - A previously healthy 5 1/2-year-old male had Reye syndrome. He presented in coma
      with apnea 1 week after a viral infection and following 2 days of vomiting and
      progressive obtundation. He was in coma with dystonic posturing and intact
      brainstem function. Laboratory evaluation revealed initial hypoglycemia, and
      markedly elevated liver enzymes, prolonged clotting times, and elevated ammonia
      levels. No underlying metabolic disorder was present, and the patient completely
      recovered. On a modified diffusion-weighted image magnetic resonance imaging
      scan, restriction of diffusion in the thalamus and midbrain was observed. While
      abnormalities of the thalamus and midbrain have previously been reported, this is
      the first report of diffusion-weighted imaging indicating early impairment of
      water diffusion, a finding more commonly observed with stroke.

PMID- 16648005
TI  - Bilateral traumatic carotid artery dissection in a child.
AB  - Traumatic dissection of the carotid artery is an infrequent but serious
      complication of blunt craniocervical injury. There is controversy regarding the
      need for diagnostic screening and management. This report presents a child with
      delayed neurologic symptoms and multiple cerebral infarcts secondary to bilateral
      extracranial traumatic carotid artery dissection. The pathophysiology, clinical
      presentation, and treatment options of blunt carotid artery trauma are discussed.

PMID- 16648006
TI  - The magnetoencephalographic response to upright and inverted face stimuli in a
      patient with Williams syndrome.
AB  - The processing of faces in a patient with Williams syndrome was investigated
      using magnetoencephalography by evaluating responses to upright and inverted face
      stimuli. His processing of upright faces was not different from that of healthy
      adults. However, the processing of inverted faces was faster than those of
      healthy adults and faster than his processing of upright faces. The result
      indicated the absence of face inversion effect usually observed in healthy
      adults.

PMID- 16648007
TI  - Retrospective diagnosis of congenital cytomegalovirus infection using umbilical
      cord.
AB  - Approximately 90% of infants congenitally infected with cytomegalovirus are
      asymptomatic at birth, but a number of them later develop central nervous system
      disorders. However, diagnosis of congenital infection with virologic or serologic
      evidence had been almost impossible beyond the neonatal period. Recently, dried
      blood spots on Guthrie cards have been demonstrated to be useful for
      retrospective diagnosis of congenital cytomegalovirus infection; however, they
      are usually stored for only 1 year. In Japan, the umbilical cord is kept clean
      and dry as a symbol of the mother-to-child bond, and in recent studies,
      cytomegalovirus deoxyribonucleic acid was successfully detected from dried
      umbilical cord of two 1-year-old children who were clinically suspected of having
      had congenital cytomegalovirus infection. This report describes a 4-year-old male
      with various central nervous system disorders who was diagnosed with congenital
      cytomegalovirus infection by detecting cytomegalovirus deoxyribonucleic acid from
      dried umbilical cord.

PMID- 16648008
TI  - Compulsive masturbation in infantile autism treated by mirtazapine.
AB  - This case report describes a child with a severe autistic syndrome worsened by
      hypersexual behavior consisting of compulsive masturbatory activity. Selective
      serotonin reuptake inhibitors have been reported to be beneficial in reducing
      hypersexual behaviors. A treatment with mirtazapine improved the entire clinical
      autistic picture with the disappearance of masturbation. This result suggests
      that selective serotonin reuptake inhibitors could be useful and promising tools
      in the treatment of hypersexual behaviors in children with autistic disorders.
      Moreover, the general, and in some ways unexpected, improvement of the social
      interaction, communication, and imagination, the dramatic reduction of aloof
      mannerisms, stereotypes, aggressiveness, and inappropriate emotional response to
      frustrations, as well as the first appearance of the pragmatic use of language
      and a strong impetus to emotional development disclosed a new spectrum of
      possible applications of these drugs, and mirtazapine in particular, suggesting
      the need for new and more extensive studies on the pharmacotherapy of autism.

PMID- 16648009
TI  - The emergency department (ED).

PMID- 16648010
TI  - Consequences of targeted parathyroidectomy guided by localization studies without
      intraoperative parathyroid hormone monitoring.
AB  - BACKGROUND: After excision of an abnormal gland, the dynamics of intraoperative
      parathyroid hormone (PTH) levels signal whether or not more hypersecreting tissue
      is present. This quantitative assurance of operative success has led to targeted
      exploration of the hyperfunctioning gland(s). Some have questioned the need for
      intraoperative PTH monitoring (IPM) in the presence of positive nuclear scanning.
      The purpose of this study was to examine the accuracy of nuclear scans in
      correctly localizing and guiding the complete excision of all abnormal gland(s)
      in patients with sporadic primary hyperparathyroidism (SPHPT) and to demonstrate
      how IPM changed the operative management in these patients. STUDY DESIGN: Five
      hundred nineteen consecutive patients with sporadic primary hyperparathyroidism
      had technetium 99-m-sestamibi scans (MIBI) as localization studies obtained
      before undergoing parathyroidectomy guided exclusively by IPM. All patients were
      either followed for more than 6 months, or their procedures were identified as
      operative failures. MIBI reports were correlated with operative findings, hormone
      dynamics, and postoperative outcomes. RESULTS: Operative success was achieved in
      506 of 519 patients (97%). MIBI correctly localized all involved glands in 411
      patients (80%). Among the 105 patients (20%) with incorrect or negative scans,
      IPM changed the operative management in 86 of 105 (82%) by pointing out
      incomplete resection in patients with a single MIBI incorrect focus (21 of 28) or
      unrecognized multiglandular disease by scan (13 of 15); avoiding unnecessary
      exploration in patients with additional incorrect foci (20 of 21); and guiding
      the surgeon to successful excision or unilateral neck exploration in patients
      with negative MIBI (32 of 41). CONCLUSIONS: MIBI as a single adjunct missed 87%
      of patients with multiglandular disease. Including patients with negative (8%)
      and incorrect (12%) MIBI, IPM changed the operative management in 17% of patients
      and led to operative success in 97%. We suggest that IPM should be used to guide
      parathyroid excision in every patient with sporadic primary hyperparathyroidism.

PMID- 16648011
TI  - Risk factors for pancreatic anastomotic leakage: the significance of preoperative
      dynamic magnetic resonance imaging of the pancreas as a predictor of leakage.
AB  - BACKGROUND: The histologic degree of pancreatic fibrosis can be assessed
      preoperatively by using the time-signal intensity curve (TIC) of the pancreas
      obtained from dynamic magnetic resonance imaging. STUDY DESIGN: To identify risk
      factors for postoperative pancreatic anastomotic leakage and to assess the impact
      of pancreatic TIC on this complication, 89 patients who underwent a pancreatic
      head resection with an end-to-side pancreaticojejunostomy between December 1998
      and August 2005 were retrospectively reviewed. The pancreatic TIC profiles were
      classified into 3 types: type I, indicating a normal pancreas without fibrosis;
      and types II and III indicating fibrotic pancreas. RESULTS: Pancreaticojejunal
      anastomotic leakage occurred in 14 patients (16%). In a univariate analysis,
      pancreatic texture (hard, 3% versus intermediate, 20% versus soft, 23%; p =
      0.046), pancreatic duct size (> 3 mm, 8% versus <or= 3 mm, 25%; p = 0.037), and
      pancreatic TIC (types II, III, 3% versus type I, 25%; p = 0.006) were notably
      associated with pancreatic anastomotic leakage. In a multivariable analysis,
      pancreatic TIC (odds ratio [OR], 9.58; 95% CI, 1.1 to 91.7) was the only marked
      independent predictor of postoperative pancreatic leakage. A subanalysis of 52
      patients with type I pancreatic TIC demonstrated hemoglobin A1c (odds ratio,
      9.81; 95% CI, 1.2 to 127.9) to be a notable predictor of leakage and pancreatic
      leakage developed in diabetic patients with a high hemoglobin A1c concentration
      (> 6.0%) than in those with a normal hemoglobin A1c level. CONCLUSIONS:
      Pancreatic TIC from dynamic MRI provides reliable information for predicting risk
      of pancreatic anastomotic leakage after pancreatic head resection. Especially in
      patients with type I pancreatic TIC, the presence of uncontrolled diabetes is
      considered a primary risk factor for postoperative pancreatic leakage.

PMID- 16648012
TI  - Number of lymph node metastases is better predictor of prognosis than level of
      lymph node metastasis in patients with node-positive colon cancer.
AB  - BACKGROUND: Lymph node metastasis is the most important prognostic factor for
      colon cancer patients. Survival is also related to the number and level of
      positive lymph nodes (PLNs). Definitions of degree of PLNs for colon cancer
      differ greatly between the number and level of PLNs. STUDY DESIGN: The aim of
      this study is to compare number and level of PLNs to see which is a better
      predictor of prognosis for node-positive colon cancer. One hundred eighteen
      patients underwent histologically curative resection for node-positive colon
      cancer. We calculated the cumulative 5-year survival rates and examined
      prognostic factors for multivariate analysis based on the number and level of
      PLNs and additional factors. The number of PLNs was classified as either one to
      three PLNs or more than four PLNs, and level of PLNs was classified as either
      Level I (pericolic lymph node metastasis) or Level II (lymph node metastasis
      along the major named vessel supplying the tumor, and that around the origin of a
      main artery). RESULTS: Cumulative 5-year survival rates were statistically
      different between the 1 to 3 PLNs group and the more than 4 PLNs group, but not
      significantly different between Level I group and Level II group. Multivariate
      analysis showed that number, not level, of PLNs was an independent prognostic
      factor. CONCLUSIONS: In node-positive colon cancer, number of PLNs predicted
      prognosis better than level of PLNs.

PMID- 16648013
TI  - Impact of isolated clinical performance feedback on clinical productivity of an
      academic surgical faculty.
AB  - BACKGROUND: There is increasing financial pressure to maximize clinical
      productivity for academic physicians. We examined whether clinical performance
      feedback alone could contribute to improving the clinical productivity of
      surgeons in an academic department of surgery. STUDY DESIGN: We implemented a
      clinical performance feedback program in January 2003. We then compared clinical
      productivity in terms of relative value units (RVUs) of surgeons for 18 months
      before and 18 months after this intervention, using each surgeon as his or her
      own control. Regression was performed with dependent variable ln (monthly RVUs)
      and independent variables "calendar month," "pre/post" January 2003, and
      "surgeon." The coefficient on "pre/post" reflected average change in RVUs. We
      also surveyed faculty on their use of and attitudes toward this feedback.
      RESULTS: There was a 58% survey response. Ninety-two percent of responding
      faculty reported that they viewed and used the performance feedback, and that it
      affected their practice. Ninety-two percent believed the information accurately
      reflected their performance, 89% thought that the comparisons were useful, and
      79% desired more feedback information, specifically, comparisons with external
      benchmarks. When RVU data were examined, the coefficient on change pre- and
      postintervention indicated a 7.4% increase in productivity (p < 0.001), or a 6.0%
      increase (p=0.003) after exclusion of outliers. CONCLUSIONS: Performance feedback
      was associated with a small (6.0%) but significant improvement in productivity in
      this academic surgical faculty group. Performance feedback can be useful and
      should be used in conjunction with other management tools for this population.

PMID- 16648014
TI  - Operating room teamwork among physicians and nurses: teamwork in the eye of the
      beholder.
AB  - BACKGROUND: Teamwork is an important component of patient safety. In fact,
      communication errors are the most common cause of sentinel events and wrong-site
      operations in the US. Although efforts to improve patient safety through
      improving teamwork are growing, there is no validated tool to scientifically
      measure teamwork in the surgical setting. STUDY DESIGN: Operating room personnel
      in 60 hospitals were surveyed using the Safety Attitudes Questionnaire. Surgeons,
      anesthesiologists, certified registered nurse anesthetists, and operating room
      nurses rated their own peers and each other using a 5-point Likert scale (1 =
      very low, 5 = very high). RESULTS: Overall response rate was 77.1% (2,135 of
      2,769). Ratings of teamwork differed substantially by operating room caregiver
      type, with the greatest differences in ratings shown by physicians: surgeons
      (F[4, 2058] = 41.73, p < 0.001), and anesthesiologists (F[4, 1990] = 53.15, p <
      0.001). The percent of operating room caregivers rating the quality of
      collaboration and communication as "high" or "very high" was different by
      caregiver role and whether they were rating a peer or another type of caregiver:
      surgeons rated other surgeons "high" or "very high" 85% of the time, and nurses
      rated their collaboration with surgeons "high" or "very high" only 48% of the
      time. CONCLUSIONS: Considerable discrepancies in perceptions of teamwork exist in
      the operating room, with physicians rating the teamwork of others as good, but at
      the same time, nurses perceive teamwork as mediocre. Given the importance of
      communication and collaboration in patient safety, health care organizations
      should measure teamwork using a scientifically valid method. The Safety Attitudes
      Questionnaire can be used to measure teamwork, identify disconnects between or
      within disciplines, and evaluate interventions aimed at improving patient safety.

PMID- 16648015
TI  - Relationship between provider volume and postoperative complications for
      bariatric procedures in New York State.
AB  - BACKGROUND: Although the number of bariatric procedures has grown recently, few
      studies have focused on the relationship between provider volume and outcomes
      among patients undergoing a bariatric procedure. STUDY DESIGN: Using New York
      State's inpatient discharge database, we identified adults undergoing a bariatric
      procedure in New York State between January 1, 2003 and December 31, 2003
      (n=7,868). Separate multivariable statistical models were constructed to examine
      the relationship between surgeon volume and hospital volume and postoperative
      complications (using surgeon volume cutpoints of 25, 50, 100, 150 and hospital
      volume cutpoints of 100, 125, 150, 200) while controlling for demographic
      characteristics and comorbidity. RESULTS: There was a considerably higher
      likelihood of postoperative complications among surgeons performing 100 or fewer
      bariatric procedures compared with those performing more than 100 procedures
      (odds ratio [OR]: 2.39, 95% CI: 1.59 to 3.59) and for those performing 150 or
      fewer procedures compared with those performing more than 150 procedures (odds
      ratio: 2.05, 95% CI: 1.29 to 3.25) after risk adjustment. Likewise, for each of
      the four hospital volume cutpoints, there was a notably higher likelihood of
      postoperative complications in the lower volume hospitals. Analyses of the
      interaction between surgeon and hospital volume indicated a markedly higher
      likelihood of postoperative complications among patients operated on by a low
      volume surgeon (100 procedures or fewer) in a low-volume hospital (150 procedures
      or fewer) or a low-volume surgeon in a high-volume hospital than among patients
      operated on by a high-volume surgeon in a high-volume hospital. CONCLUSIONS: The
      likelihood of postoperative complications from bariatric procedures is greater
      for patients with low-volume surgeons or in low-volume hospitals.

PMID- 16648016
TI  - Early definitive abdominal closure using serial closure technique on injured
      soldiers returning from Afghanistan and Iraq.
AB  - BACKGROUND: Twenty-nine of 1,284 battle-injured soldiers arriving at Walter Reed
      Army Medical Center from Operations Enduring Freedom and Iraqi Freedom have
      abdominal wounds requiring delayed definitive closure with Gore-Tex (WL Gore &
      Assoc) mesh. METHODS: Serial abdominal closure (SAC) leading to early definitive
      abdominal closure (EDAC) was achieved using Gore-Tex mesh. Inpatient records of
      Operations Enduring Freedom and Iraqi Freedom soldiers with open or reopened
      abdomens were reviewed from March 2003 to August 2005. RESULTS: Twenty-nine
      soldiers, average age 27 years (range 20 to 42 years) injured by secondary blast
      effects (n = 19); penetrating (n = 8); motor vehicle crashes (n = 1); and
      crushing injury (n = 1) were included in the study. Patients arrived at Walter
      Reed Army Medical Center 8 days (range 3 to 56 days) after injury with Gore-Tex
      mesh placed 6 days (range 0 to 26 days) from arrival and 14 days (range 4 to 79
      days) from injury. SAC was achieved with towel clamp tightening or excision of
      midline mesh and drawing fascia closer to the midline for an average of 46 days
      (range 15 to 160 days) before EDAC. One patient is undergoing SAC and another was
      transferred to another facility. EDAC was achieved in 24 of the remaining of 27
      patients (89%). Four patients required early removal of the Gore-Tex mesh,
      resulting in three patients with planned ventral hernia. One patient underwent
      EDAC with primary closure and fascial release. EDAC was completed with
      polypropylene mesh in 17 patients and 6 patients had original Gore-Tex in place.
      Patients were discharged from the hospital an average of 18 days after closure
      (range 1 to 89 days) with total hospital days of 62 (range 17 to 197 days).
      Average followup of patients from placement of Gore-Tex mesh is 264 days (range
      31 to 855 days). CONCLUSIONS: SAC with Gore-Tex mesh led to EDAC in 89% of
      patients and proved to be a safe and effective alternative to planned ventral
      hernia. SAC allowed protection of abdominal contents, effective fluid management,
      reclamation of abdominal domain, and early rehabilitation with minimal
      complications and only one hernia reoccurrence.

PMID- 16648017
TI  - Does gum chewing ameliorate postoperative ileus? Results of a prospective,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: A preliminary report has been interpreted to suggest that gum chewing
      reduces duration of postcolectomy ileus. STUDY DESIGN: We rigorously tested this
      hypothesis in a prospective, randomized, placebo-controlled study. Patients
      undergoing open colectomy (n = 66) were randomized to receive 1 of 3
      postoperative regimens beginning on postoperative day 1: sips (control, n = 21);
      sips and accupressure wrist bracelet (placebo, n = 23); and sips and gum chewing
      (treatment, n = 22). Patients were unaware of which regimen constituted placebo
      or treatment; end points were assessed by blinded investigators. Power was set a
      priori at 85% to detect a 0.75-day difference in time to first postoperative
      passage of flatus between placebo and treatment groups. Groups were compared
      using the log-rank test. RESULTS: Groups were equivalent with respect to
      demographic and surgical characteristics. Median times to first postoperative
      passage of flatus were as follows: sips, 67 hours; bracelet and sips, 72 hours;
      gum and sips, 60 hours (p = 0.384). There were no significant differences in time
      to passage of first bowel movement, time until patients were ready for discharge,
      or time until actual discharge among the three groups. Inpatient and 30-day
      followup demonstrated no difference in frequency or distribution of postoperative
      complications. CONCLUSIONS: In contrast to findings of a preliminary study, our
      clinical trial suggests that gum chewing, although safe, does not reduce duration
      of postcolectomy ileus.

PMID- 16648018
TI  - Construct validity testing of a laparoscopic surgical simulator.
AB  - BACKGROUND: We present initial data on the construct, content, and face validity
      of the LAPMentor (Simbionix), virtual reality laparoscopic surgical simulator.
      STUDY DESIGN: Medical students (MS), residents and fellows (R/F), and experienced
      laparoscopic surgeons (ES), with < 30 laparoscopic cases per year (ES<30) and
      those with > 30 laparoscopic cases per year (ES>30), were tested on 9 basic skill
      tasks (SK) including manipulation of 0-degree and 30-degree cameras (SK1, SK2),
      eye-hand coordination (SK3), clipping (SK4), grasping and clipping (SK5), two
      handed maneuvers (SK6), cutting (SK7), fulguration (SK8), and object
      translocation (SK9). RESULTS: Mean MS (n=23), R/F (n=24), ES<30 (n=26), and ES>30
      (n=30) ages were 26 years (range 21 to 32 years), 31 years (range 27 to 39
      years), 49 years (range 31 to 70 years) and 47 years (range 34 to 69 years),
      respectively. In the lower level skill tasks (SK3, SK4, SK5, and SK6) the ES>30,
      ES<30, and R/F had similar scores, but were all substantially better than the MS
      scores. In the higher level skill tasks (SK7, SK8, and SK9), the ES>30 scores
      tended to be better than the R/F and ES<30, which were similar, and these, in
      turn, were markedly better than the MS. The ES>30 had notably higher SK8 scores
      than the R/F and ES<30, who had similar scores, and these had notably better
      scores than the MS. CONCLUSIONS: The noncamera skills (SK3 to 9) of the LAPMentor
      surgical simulator can distinguish between laparoscopically naive and ES. SK8
      showed the highest level of construct validity, by accurately differentiating
      among the MS, R/F, ES<30 and ES>30.

PMID- 16648019
TI  - Peptide YY attenuates STAT1 and STAT3 activation induced by TNF-alpha in acinar
      cell line AR42J.
AB  - BACKGROUND: STAT1 and STAT3, members of the cytoplasmic family of signal
      transducers and activators of transcription factors (STAT), have been associated
      with numerous inflammatory pathologies, including inflammatory bowel disease,
      hepatitis, and acute lung injury. But little is known about their role in the
      pancreas. Peptide YY (PYY), an inhibitory gastrointestinal hormone, ameliorates
      pancreatitis in vivo and in vitro. In addition, we have shown that PYY attenuates
      transcription factors, such as nuclear transcription factor (NF)-kappaB and
      Smad3/4, which mediate inflammation. We hypothesized that tumor necrosis factor
      (TNF)-alpha would induce STAT1 and STAT3, and PYY would attenuate their
      transcription factor binding. STUDY DESIGN: Rat pancreatic acinar cells were
      treated with recombinant TNF-alpha (200 ng/mL); PYY (3-36; 500 pM) was added 30
      minutes post-TNF-alpha treatment. Cells were harvested at 2 hours, and nuclear
      protein and conditioned media were extracted. Levels of amylase secretion and
      cytokine production were measured using commercially available kits. STAT
      transcription factor binding was determined by protein/DNA array analysis and
      densitometry; results were verified again by electrophoretic mobility shift assay
      (EMSA) and ELISA-based assay. RESULTS: Amylase production was considerably
      increased (p < 0.05) as early as 5 minutes after addition of exogenous TNF-alpha
      and remained elevated for 24 hours. PYY decreased amylase production to control
      levels. A notable increase (p < 0.05) in the production of cytokines interleukin
      (IL)-1beta, IL-4, IL-6, IL-10, and TNF-alpha was observed with TNF-alpha
      treatment; production was reduced with PYY. TNF-alpha substantially upregulated
      STAT1 and STAT3 (two-fold or greater); PYY downregulated their binding activity
      to control levels. Results from both the electrophoretic mobility shift assay-
      and the ELISA-based assays verified STAT1 and STAT3 responses to TNF-alpha and
      PYY. CONCLUSIONS: In pancreatic acinar cells, TNF-alpha activated STAT1 and
      STAT3, known mediators of inflammatory cytokines. Interestingly, PYY attenuated
      their protein/DNA binding, which may have an impact on development of the
      disease. Additional investigation of STAT proteins and PYY could provide new
      therapeutic strategies for pancreatitis.

PMID- 16648020
TI  - Preconditioning versus postconditioning: mechanisms and therapeutic potentials.

PMID- 16648021
TI  - Green tea, the "Asian paradox," and cardiovascular disease.

PMID- 16648022
TI  - Enhancing the use of clinical guidelines: a social norms perspective.

PMID- 16648023
TI  - Nutritional assessment of surgery patients.

PMID- 16648024
TI  - Multiple intussusceptions after aortic aneurysm repair.

PMID- 16648025
TI  - A case of sibling rivalry?

PMID- 16648026
TI  - Video-assisted thoracic surgery removal of foreign bodies after penetrating chest
      trauma.

PMID- 16648028
TI  - Preoperative skin preparation.

PMID- 16648029
TI  - Delayed massive hemorrhage after pancreaticoduodenectomy: a new therapeutic
      approach.

PMID- 16648030
TI  - Does the TNM staging system for esophageal cancer need revision?

PMID- 16648031
TI  - Use of resterilized polypropylene mesh in inguinal hernia repair.

PMID- 16648033
TI  - John F Kennedy's tracheostomy.

PMID- 16648035
TI  - Expect the unexpected.

PMID- 16648036
TI  - Keynote comment: why the lack of progress for oral cancer?

PMID- 16648037
TI  - Rituximab for early-stage diffuse large-B-cell lymphoma.

PMID- 16648038
TI  - Improving resection of malignant glioma.

PMID- 16648039
TI  - Is screening mammography safe for high-risk patients?

PMID- 16648040
TI  - The role of immunochemical testing for colorectal cancer.

PMID- 16648041
TI  - Helicobacter pylori and prognosis of gastric carcinoma.

PMID- 16648042
TI  - CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in
      young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised
      controlled trial by the MabThera International Trial (MInT) Group.
AB  - BACKGROUND: The role of rituximab in combination with different CHOP
      (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy
      regimens in young patients with good-prognosis diffuse large-B-cell lymphoma
      remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab
      with CHOP-like chemotherapy alone in these patients. METHODS: 824 patients who
      were from 18 countries; aged 18-60 years; and who had no risk factors or one risk
      factor according to age-adjusted International Prognostic Index (IPI), stage II
      IV disease, or stage I disease with bulk were enrolled. These patients were
      randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413)
      or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal
      sites received additional radiotherapy. The primary endpoint was event-free
      survival; secondary endpoints were response, progression under therapy,
      progression-free survival, overall survival, and frequency of toxic effects.
      Analyses were done by intention to treat and per protocol. This trial is
      registered at http://www.clinicaltrials.gov, NCT 00064116. FINDINGS: After a
      median follow-up of 34 months (range 0.03-61), patients assigned chemotherapy and
      rituximab had increased 3-year event-free survival compared with those assigned
      chemotherapy alone (79% [95% CI 75-83] vs 59% [54-64]; difference between groups
      20% [13-27], log-rank p<0.0001), and had increased 3-year overall survival (93%
      [90-95] vs 84% [80-88]; difference between groups 9% [3-13], log-rank p=0.0001).
      Event-free survival was affected by treatment group, presence of bulky disease,
      and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup
      (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1
      or bulk, or both). Groups did not differ in the frequency of adverse events.
      INTERPRETATION: Rituximab added to six cycles of CHOP is an effective treatment
      for young patients with good-prognosis diffuse large-B-cell lymphoma. The
      definition of two prognostic subgroups allows for a more refined therapeutic
      approach for these patients.

PMID- 16648043
TI  - Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant
      glioma: a randomised controlled multicentre phase III trial.
AB  - BACKGROUND: 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to
      intracellular accumulation of fluorescent porphyrins in malignant gliomas-a
      finding that is under investigation for intraoperative identification and
      resection of these tumours. We aimed to assess the effect of fluorescence-guided
      resection with 5-aminolevulinic acid on surgical radicality, progression-free
      survival, overall survival, and morbidity. METHODS: 322 patients aged 23-73 years
      with suspected malignant glioma amenable to complete resection of contrast
      enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic
      acid for fluorescence-guided resection (n=161) or to conventional microsurgery
      with white light (n=161). The primary endpoints were the number of patients
      without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h
      after surgery) and 6-month progression-free survival as assessed by MRI.
      Secondary endpoints were volume of residual tumour on postoperative MRI, overall
      survival, neurological deficit, and toxic effects. We report the results of an
      interim analysis with 270 patients in the full-analysis population (139 assigned
      5-aminolevulinic acid, 131 assigned white light), which excluded patients with
      ineligible histological and radiological findings as assessed by central
      reviewers who were masked as to treatment allocation; the interim analysis
      resulted in termination of the study as defined by the protocol. Primary and
      secondary endpoints were analysed by intention to treat in the full-analysis
      population. The study is registered at http://www.clinicaltrials.gov as
      NCT00241670. FINDINGS: Median follow-up was 35.4 months (95% CI 1.0-56.7).
      Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients
      assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light
      (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5
      aminolevulinic acid had higher 6-month progression free survival than did those
      allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between
      groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the
      frequency of severe adverse events or adverse events in any organ system class
      reported within 7 days after surgery. INTERPRETATION: Tumour fluorescence derived
      from 5-aminolevulinic acid enables more complete resections of contrast-enhancing
      tumour, leading to improved progression-free survival in patients with malignant
      glioma.

PMID- 16648044
TI  - Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation
      carriers: a case-control study.
AB  - BACKGROUND: Screening mammography is associated with a small dose of radiation to
      the breast, and women with increased genetic risk might be particularly sensitive
      to the DNA-damaging effects of ionising radiation. We aimed to assess whether
      exposure to ionising radiation through mammography screening was associated with
      risk of breast cancer in BRCA1 or BRCA2 mutation carriers. METHODS: We identified
      1600 cases of breast cancer and 1600 controls without breast cancer who were
      matched for BRCA mutation, date of birth (within 1 year), and country of
      residence from an international registry of BRCA1 and BRCA2 mutation carriers. We
      used a questionnaire to inquire about whether participants had ever had screening
      mammography, and, if so, the age at which they first had the procedure. RESULTS:
      We found no association between ever having screening mammography and risk of
      breast cancer (odds ratio [OR] 1.03 [95% CI 0.85-1.25], adjusted for parity, oral
      contraceptive use, ethnic origin, and bilateral oophorectomy). The association
      was much the same for BRCA1 mutation carriers and BRCA2 mutation carriers (1.04
      [0.84-1.29] vs 1.06 [0.67-1.66], respectively, adjusted for parity, oral
      contraceptive use, ethnic origin, and bilateral oophorectomy). INTERPRETATION:
      These findings do not lend support to the idea that exposure to ionising
      radiation through routine screening mammography contributes substantially to the
      burden of breast cancer in BRCA1 and BRCA2 mutation carriers. Prospective studies
      are needed to confirm the results of this initial report, and, where possible,
      these studies should assess a more appropriate endpoint of total exposure.

PMID- 16648045
TI  - Image-guided breast brachytherapy: an alternative to whole-breast radiotherapy.
AB  - Lumpectomy and whole-breast radiotherapy (ie, breast-conservation treatment) are
      accepted as viable alternatives to mastectomy in locoregional management of
      breast cancer. These techniques are used to keep morbidity to a minimum, optimise
      cosmesis, and maintain treatment outcomes. Pathological and clinical data suggest
      that most recurrences of cancer in the ipsilateral breast are in the vicinity of
      the index lesion, and that remote recurrences are uncommon, whether or not whole
      breast radiotherapy is delivered. These data lend support to the idea of partial
      breast radiotherapy. Such a restricted treatment volume allows safe delivery of
      an accelerated hypofractionated regimen over a shortened course of 1 week. This
      technique differs from that of standard whole-breast tangential external-beam
      radiotherapy and necessitates investigation of accelerated partial-breast
      irradiation (APBI). Several techniques of APBI are being investigated; however,
      most experience, and the most favourable early outcomes, has been obtained with
      image-guided breast brachytherapy. This review highlights the rationale and
      outcomes of brachytherapy techniques.

PMID- 16648046
TI  - Non-small-cell lung cancer and breast carcinoma: chemotherapy and beyond.
AB  - Early screening, adjuvant and sequential systemic treatment, and hormonal therapy
      have benefits in treatment of breast cancer. Management of non-small-cell lung
      cancer (NSCLC) is progressing and will hopefully follow in the same footsteps as
      that of breast cancer. Only recently have clinical trials established adjuvant
      treatment as the standard of care in lung cancer. A growing number of effective
      cytotoxic and targeted agents have resulted in increased survival when used as
      sequential treatment in both breast cancer and NSCLC. The interaction between
      oestrogen receptors (ER) in the lung and epidermal growth factor receptor (EGFR)
      suggests a potential role for endocrine manipulation in the treatment of NSCLC.
      This complex interaction involves several types of ER receptors and different
      signalling pathways. Interactions between tobacco and oestrogen confound the
      effects of exogenous oestrogens on risk of lung cancer, but not on that of breast
      cancer. The optimum application of hormonal manipulation to prevent or treat lung
      cancer will depend on a more-complete understanding of lung-specific ER
      signalling. Early trials have assessed the interaction between the ER and EGFR
      signalling.

PMID- 16648047
TI  - Glucocorticoid use in prostate cancer and other solid tumours: implications for
      effectiveness of cytotoxic treatment and metastases.
AB  - Glucocorticoids have been used widely in conjunction with other treatment for
      patients with cancer because they have potent proapoptotic properties in lymphoid
      cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue.
      However, glucocorticoids are used in a supportive-care role, even though to our
      knowledge no prospective clinical studies have assessed the effect of these
      steroids on the growth of solid tumours. Data from preclinical and, to some
      extent, clinical studies, suggest that glucocorticoids induce treatment
      resistance in solid tumours, including prostate cancer. Research has focussed on
      disseminated cells that have been shed by the tumour: the potential of
      glucocorticoids to render these cells resistant to apoptosis--and to downregulate
      the immune response--might contribute to tumour metastasis. Here, we review the
      benefits of glucocorticoids and their negative effects, such as induction of
      resistance in tumour cells and concomitant induction of apoptosis in immune
      cells, with particular emphasis on prostate cancer.

PMID- 16648048
TI  - Cancer risk from exposure to galactic cosmic rays: implications for space
      exploration by human beings.
AB  - Space programmes are shifting toward planetary exploration, and in particular
      towards missions by human beings to the moon and Mars. However, exposure to space
      radiation is an important barrier to exploration of the solar system by human
      beings because of the biological effects of high-energy heavy ions. These ions
      have a high charge and energy, are the main contributors to radiation risk in
      deep space, and their biological effects are understood poorly. Predictions of
      the nature and magnitude of risks posed by exposure to radiation in space are
      subject to many uncertainties. In recent years, worldwide efforts have focussed
      on an increased understanding of the oncogenic potential of galactic cosmic rays.
      A review of the new results in this specialty will be presented here.

PMID- 16648049
TI  - Aplastic anaemia in patient with glioblastoma multiforme treated with
      temozolomide.

PMID- 16648050
TI  - Spontaneous complete regression of hepatic epithelioid haemangioendothelioma.

PMID- 16648051
TI  - Ileouterine fistula after primary treatment of advanced endometrial cancer.

PMID- 16648052
TI  - Anatomic characterization of endocardial substrate for hemodynamically stable
      reentrant ventricular tachycardia: identification of endocardial conducting
      channels.
AB  - BACKGROUND: Detailed anatomic characterization of endocardial substrate of
      ventricular tachycardia (VT) is limited. OBJECTIVES: The purpose of this study
      was to determine the endocardial dimensions and local electrogram voltage
      characteristics of the reentrant circuit. VT-related conducting channels
      corresponding to zones of slow conduction may be identified. METHODS:
      Electroanatomic mapping was performed in 26 patients with uniform VT. Entrainment
      mapping was performed in 53 VTs, of which 19 entrance, 37 isthmus, 48 exit, and
      32 outer loop sites were identified. The color display of voltage maps was
      adjusted to identify conducting channels associated with VT circuits. A
      conducting channel was defined as a path of multiple orthodromically activated
      sites within the VT circuit that demonstrated an electrogram amplitude higher
      than that of surrounding areas as evidenced by voltage color differences.
      RESULTS: Forty-seven (84%) of 56 entrance or isthmus sites were located within
      dense scar (<0.5 mV). Nearly all exits (92%) were located in abnormal endocardium
      (<1.5 mV), with more than half (54%) located in the border zone (0.5-1.5 mV). VT
      related conducting channels was identified in 18 of 32 VTs with detailed mapping
      (average length 32 +/- 22 mm). The voltage threshold in the conducting channels
      ranges from 0.1 to 0.7 mV (mean 0.33 +/- 0.15 mV). CONCLUSION: (1) Most entrance
      and isthmus sites of hemodynamically stable VT are located in dense scar, whereas
      exits are located in the border zone. (2) VT-related conducting channels may be
      identified by careful voltage threshold adjustment. These findings have important
      implications regarding strategies for substrate-based VT ablation.

PMID- 16648053
TI  - Target sites for catheter ablation of unmappable ventricular tachycardia during
      sinus rhythm.

PMID- 16648054
TI  - Entrainment mapping for rapid distinction of left and right atrial tachycardias.
AB  - BACKGROUND: Distinguishing left from right atrial tachycardia is a critical step
      for guiding ablation. OBJECTIVES: The purpose of this study was to develop and
      validate a simple algorithm predicting the location of macroreentrant atrial
      tachycardia (AT) circuits from limited entrainment mapping in right atrium (RA)
      and coronary sinus (CS). METHODS: In 180 patients with organized reentrant AT,
      entrainment was performed at the high RA, proximal CS, and distal CS. The
      difference between the postpacing interval (PPI) and tachycardia cycle length
      (TCL) was calculated at each site. The location of the AT reentrant circuit was
      determined by mapping and ablation. An algorithm predicting AT regions was
      developed from 104 ATs in the first 90 patients (group I) and prospectively
      evaluated in a validation cohort of 106 ATs in the second 90 patients (group II).
      RESULTS: In group I, PPI-TCL difference <50 or >50 ms at the high RA
      distinguished RA from LA reentrant circuits. For RA tachycardias, PPI-TCL
      difference at the proximal CS distinguished common flutter from lateral RA
      circuits. For LA circuits, PPI-TCL difference at the proximal and distal CS
      distinguished perimitral reentry from reentry involving the right pulmonary veins
      and septum. In group II, an algorithm based on PPI-TCL difference >50 or <50 ms
      at the high RA, proximal CS, or distal CS had sensitivity of 94%, specificity of
      88%, and predictive accuracy of 93% for predicting the successful ablation
      region. CONCLUSION: Limited entrainment from sites accessible from the RA can
      expeditiously suggest the AT location to guide more detailed mapping and
      potentially avoid unnecessary transseptal punctures in some patients.

PMID- 16648055
TI  - Simplified algorithm for localization of atrial macroreentrant tachycardias: keep
      it simple and short.

PMID- 16648056
TI  - Ablation of focal atrial arrhythmia in patients with congenital heart defects
      after surgery: role of circumscribed areas with heterogeneous conduction.
AB  - BACKGROUND: In patients late after surgical repair of congenital heart disease
      (CHD), areas with abnormal electrophysiologic properties may serve as slow
      conducting pathways within a macroreentrant circuit or may be the source of focal
      atrial tachycardia. OBJECTIVES: The purpose of this study was to evaluate the
      role of abnormal areas during focal atrial tachycardia prior to ablation.
      METHODS: Electroanatomic activation mapping of 62 atrial tachycardias was
      performed in 43 consecutive patients (37 +/- 12 years) after surgical repair of
      CHD. The mechanism of atrial tachycardia was scar related intra-atrial reentry (n
      = 27), cavotricuspid-related atrial flutter (n = 21), atrial fibrillation (n =
      2), or focal atrial tachycardia (n = 10). During intra-atrial reentry, channels
      of slow conduction could be identified in all patients. Subsequent ablation was
      directed toward connecting two nonconductive borders. The site of origin during
      focal atrial tachycardia showed fractionated potentials and/or continuous
      electrical activity. RESULTS: Ablation directed at isolating the source area
      resulted in termination of focal atrial tachycardia in all cases. In two
      patients, ablation of an area showing continuous electrical activity giving rise
      to fibrillatory conduction resulted in termination of atrial fibrillation.
      Ablation of intra-atrial reentry was successful in 70%. Atrial flutter and focal
      atrial tachycardia were successfully ablated in all patients. No complications
      were observed. CONCLUSION: In patients with surgically corrected CHD, atrial
      tachycardia most often is caused by a macroreentrant mechanism but in some is the
      result of a focal mechanism. Areas of abnormal conduction may serve not only as a
      zone of slow conduction within a macroreentrant circuit but also as the site of
      origin of a focal atrial arrhythmia. Catheter ablation directed at "source
      isolation" is effective in eliminating focal atrial tachycardia in patients with
      CHD.

PMID- 16648057
TI  - Benefit of millisecond waveform durations for patients with high defibrillation
      thresholds.
AB  - BACKGROUND: Patients with a high defibrillation threshold (DFT) present an
      atypical but vexing problem with regard to implantable cardioverter-defibrillator
      (ICD) therapy. Their implant procedures are lengthy and involve more risk of
      complications. These patients often sustain a reduced safety margin that may
      compromise their survival. OBJECTIVES: The purpose of this study was to evaluate
      the use of fixed millisecond duration model-optimized biphasic waveforms compared
      with conventional tilt-based waveforms in patients having a high DFT. METHODS: We
      compared a 65%/65% tilt biphasic waveform to a millisecond duration biphasic
      waveform based on the biphasic burping theory using a 90-microF shock capacitor.
      RESULTS: Fifty-four patients were evaluated. Mean DFT with tilt was reduced from
      11.0 +/- 5.5 J to 8.8 +/- 4.1 J, for a mean reduction of 20% (P < .0001). For the
      13 patients with tilt-based DFTs > or = 15 J, DFT was reduced from 18.7 +/- 4.1 J
      to 13.4 +/- 3.5 J, for a mean DFT reduction of 28% (P = .009). The population
      peak DFT was reduced from 29.0 J to 17.5 J, for a 41% reduction (P = .03).
      CONCLUSION: Use of simple millisecond biphasic waveforms instead of conventional
      tilt-based waveforms can lead to substantial reductions in DFT, especially in
      patients with high DFT.

PMID- 16648058
TI  - Fixed tilt or programmable pulse widths: are we creatures of habit?

PMID- 16648059
TI  - Unique electrophysiologic characteristics of atrioventricular nodal reentrant
      tachycardia with different ventriculoatrial block patterns: effects of slow
      pathway ablation and insights into the location of the reentrant circuit.
AB  - BACKGROUND: The electrophysiologic mechanisms of different ventriculoatrial (VA)
      block patterns during atrioventricular nodal reentrant tachycardia (AVNRT) are
      poorly understood. OBJECTIVES: The purpose of this study was to characterize
      AVNRTs with different VA block patterns and to assess the effects of slow pathway
      ablation. METHODS: Electrophysiologic data from six AVNRT patients with different
      VA block patterns were reviewed. RESULTS: All AVNRTs were induced after a sudden
      AH "jump-up" with the earliest retrograde atrial activation at the right
      superoparaseptum. Different VA block patterns comprised Wenckebach His-atrial
      (HA) block (n = 4), 2:1 HA block (n = 1), and variable HA conduction times during
      fixed AVNRT cycle length (CL) (n = 1). Wenckebach HA block during AVNRT was
      preceded by gradual HA interval prolongation with fixed His-His (HH) interval and
      unchanged atrial activation sequence. AVNRT with 2:1 HA block was induced after
      slow pathway ablation for slow-slow AVNRT with 1:1 HA conduction, and earliest
      atrial activation shifted from right inferoparaseptum to superoparaseptum without
      change in AVNRT CL. The presence of a lower common pathway was suggested by a
      longer HA interval during ventricular pacing at AVNRT CL than during AVNRT (n =
      5) or Wenckebach HA block during ventricular pacing at AVNRT CL (n = 1). In four
      patients, HA interval during ventricular pacing at AVNRT CL was unusually long
      (188 +/- 30 ms). Ablations at the right inferoparaseptum rendered AVNRT
      noninducible in 5 (83%) of 6 patients. CONCLUSION: Most AVNRTs with different VA
      block patterns were amenable to classic slow pathway ablation. The reentrant
      circuit could be contained within a functionally protected region around the AV
      node and posterior nodal extensions, and different VA block patterns resulted
      from variable conduction at tissues extrinsic to the reentrant circuit.

PMID- 16648060
TI  - Atrioventricular nodal reentrant tachycardia: is there a "common pathway" to
      understanding the mechanism?

PMID- 16648061
TI  - Cryoablation in pediatric atrioventricular nodal reentry: electrophysiologic
      effects on atrioventricular nodal conduction.
AB  - BACKGROUND: Cryoablation for treatment of atrioventricular nodal reentrant
      tachycardia (AVNRT) is safe and efficacious. Information on the effects of
      cryoablation on atrioventricular (AV) nodal conduction is limited. OBJECTIVES:
      The purpose of this study was to evaluate the effects of cryoablation on AV nodal
      conduction in pediatric patients with AVNRT. METHODS: We retrospectively analyzed
      electrophysiologic studies before and after successful cryoablation. Patients
      were divided into two groups: group 1 (n = 22, age 14 +/- 3 years) had baseline
      discontinuous atrial-to-His interval (AH) conduction curves; and group 2 (n = 13,
      age 12 +/- 4 years, P = .054) had continuous curves. RESULTS: At baseline, group
      1 had longer measurements of maximal AH with A1A2, AV nodal effective refractory
      period, and AV block cycle length. Postcryoablation, both group 1 and group 2
      showed decreases in maximal AH with A1A2 pacing or atrial overdrive pacing and in
      the finding of PR > or = RR with atrial overdrive pacing (group 1: 55% vs 5%, P <
      .001; group 2: 69% vs 0%, P < .001). A significant increase in overall AV
      effective refractory period and a decrease in AV block cycle length were found in
      group 1 but not group 2. Fifty percent of group 1 patients had complete abolition
      of slow pathway conduction. CONCLUSION: Successful cryoablation for treatment of
      AVNRT is associated with a reduction in PR > or = RR and with decreases in
      maximal AH with A1A2 pacing or atrial overdrive pacing. Further study is needed
      to determine the usefulness of these parameters for assessment of ablation
      efficacy or as proxies for AVNRT inducibility.

PMID- 16648062
TI  - Cryoablation versus radiofrequency ablation for treatment of pediatric
      atrioventricular nodal reentrant tachycardia: initial experience with 4-mm
      cryocatheter.
AB  - BACKGROUND: Initial reports have shown cryoablation to be safe and efficacious
      for treatment of atrioventricular nodal reentrant tachycardia (AVNRT). No direct
      comparisons of cryoablation vs radiofrequency (RF) catheter ablation in pediatric
      patients have been made. OBJECTIVES: The purpose of this study was to compare the
      outcomes of cryothermal vs RF catheter ablation for treatment of AVNRT in
      pediatric patients. METHODS: We retrospectively reviewed consecutive ablation
      procedures for treatment of AVNRT at a single arrhythmia center. The RF group
      consisted of patients who underwent RF ablation from 2002 until cryothermy became
      available. The cryoablation group consisted of patients who underwent cryothermal
      ablation from 2004 to 2005. The groups were compared for procedural and
      electrophysiologic outcomes. RESULTS: RF (n = 60, age 14 +/- 4 years) and
      cryoablation (n = 57, age 14 +/- 4 years) groups had similar demographic and
      baseline parameters. Procedural times were shorter in the RF group (RF ablation
      112 +/- 31 minutes vs cryoablation 148 +/- 46 minutes, P < .001). Fluoroscopy
      times were comparable (RF ablation 21 +/- 15 minutes vs cryoablation 20 +/- 13
      minutes, P = .77). In an intention-to-treat analysis, success of the procedure
      was 100% for RF ablation and 95% for cryoablation (P = .11). No permanent AV
      block occurred in either group. Recurrence rates were higher for the cryoablation
      group, but this did not reach statistical significance (RF ablation 2% vs
      cryoablation 8%, P = .19). CONCLUSION: Cryoablation appears to be similar to RF
      for ablation of AVNRT with respect to short-term efficacy and safety of the
      procedure in a pediatric population. Recurrence rates are higher with
      cryoablation.

PMID- 16648063
TI  - Catheter ablation for atrioventricular nodal reentry tachycardia in children: a
      time to freeze, and a time to burn.

PMID- 16648064
TI  - Effects of a rate smoothing algorithm for prevention of ventricular arrhythmias:
      results of the Ventricular Arrhythmia Suppression Trial (VAST).
AB  - BACKGROUND: Rate smoothing, which is available in some pacemakers and implantable
      cardioverter defibrillators (ICDs), has been used to prevent Torsades de Pointes
      in patients with long QT syndrome. Its efficacy in general ventricular arrhythmia
      prevention has not been determined. OBJECTIVES: The purpose of the Ventricular
      Arrhythmia Suppression Trial (VAST) was to prospectively investigate whether rate
      smoothing could significantly reduce the incidence of ventricular
      tachyarrhythmias in a large, broad population of patients with ICDs. METHODS:
      Five hundred sixty-nine patients were enrolled at 57 participating centers and
      implanted with a commercially available Guidant ICD. A single-blinded crossover
      design was used in which each patient was randomized at implant to one of two
      treatment sequences: either rate smoothing on (RS On) followed by rate smoothing
      off (RS Off), or RS Off followed by RS On. This mode sequence was randomly
      determined and assigned in a 1:1 fashion using randomized permuted blocks by
      site. Each mode was followed for 6 months. Programming of rate smoothing was
      prescribed as 12% Down and 12% Up for the duration of the RS On period. RESULTS:
      Of enrolled patients, 281 were randomized to RS Off followed by RS On, and 288 to
      RS On followed by RS Off. With RS On, 75 (23%) patients experienced a reduction
      in arrhythmias, 76 (23%) saw an increase in arrhythmias, and the remaining 176
      (54%) had no difference. No significant difference (P = .58) in frequency of
      arrhythmias with RS On vs RS Off was found. CONCLUSION: Rate smoothing does not
      result in a reduction in ventricular arrhythmias in a heterogeneous population of
      patients receiving ICDs.

PMID- 16648065
TI  - Pacing for prevention of ventricular arrhythmias: time for a pause.

PMID- 16648066
TI  - Characterization of the relationship between preshock state and virtual electrode
      polarization-induced propagated graded responses resulting in arrhythmia
      induction.
AB  - BACKGROUND: Studies have demonstrated that failed defibrillation shocks often are
      followed by an electrically quiescent period (isoelectric window); however, the
      underlying mechanisms remain incompletely understood. We recently suggested a new
      mechanism termed "virtual electrode polarization-induced propagated graded
      responses" (VEPiPGRs) that might play a role in the origin of the global
      postshock activation following the isoelectric window. OBJECTIVES: The purpose of
      this study to elucidate the circumstances under which VEPiPGR activations
      originate for shocks given to paced right ventricular preparations. Specifically,
      we examined the dependence of VEPiPGRs on coupling interval (CI) and shock
      polarity and whether VEPiPGRs emerge preferentially on the epicardium or the
      endocardium. METHODS: Simultaneous endocardial and epicardial activity in
      isolated right ventricular preparations (n = 4) was imaged optically following
      shocks of strength +/-5A. All VEPiPGRs were analyzed, and the time T from shock
      end to activation onset was recorded (isoelectric window is the smallest T among
      activations that propagated globally). RESULTS: VEPiPGR activations occurred for
      CIs in the range from 80 to 150 ms. Average duration of T was 64.5 +/- 18.15 ms,
      with T decreasing as CI increased (Tmax = 82 ms, Tmin = 46 ms, linear-fit slope =
      -0.675). The average earliest CI at which cathodal (+5A) shocks resulted in
      VEPiPGRs was 87 ms compared with 116 ms for anodal (-5A) shocks. All VEPiPGR
      activations emerged first on the epicardium in a focal pattern, and all induced
      ventricular fibrillation. CONCLUSION: The global activation that terminates the
      isoelectric window could result from VEPiPGRs that find an exit pathway. VEPiPGRs
      originate at the sites of maximum action potential abbreviation by the shock,
      always on the epicardium for the preparation used here.

PMID- 16648067
TI  - Ventricular tachyarrhythmia induction by strong cardiac shocks: can understanding
      underlying mechanisms lead to improved prevention of defibrillator failure?

PMID- 16648068
TI  - Ablation of atrioventricular conduction in corrected transposition of the great
      arteries.

PMID- 16648069
TI  - Natural history of postoperative heart block in congenital heart disease:
      implications for pacing intervention.
AB  - After half a century of major progress in congenital heart disease management,
      atrioventricular conduction block continues to complicate 1-3% of surgical
      procedures. Unless treated with an implanted pacemaker, permanent postoperative
      heart block is associated with 28-100% mortality. Postoperative heart block often
      proves to be transient, typically resolving within 10 days of onset. The duration
      of postoperative heart block is widely used as a key determinant for permanent
      pacemaker implantation. Current professional pacemaker implantation guidelines
      are largely based on this criterion. However, available natural history data
      suggest that other factors, such as residual conduction system injury, likely
      play a role in increasingly recognized cases of very late postoperative mortality
      and morbidity in patients who have experienced transient postoperative heart
      block. As growing numbers of congenital heart disease patients survive into
      adulthood, and artificial pacemaking capabilities continue to improve, it might
      be necessary to reconsider and refine currently accepted pacing indications for
      postoperative heart block.

PMID- 16648070
TI  - Historical observation on commotio cordis.

PMID- 16648071
TI  - Substrate-based endocardial ablation of postinfarction ventricular tachycardia.

PMID- 16648072
TI  - Left bundle branch block during orthodromic reciprocating tachycardia: where is
      the accessory pathway?

PMID- 16648073
TI  - Pacemaker troubleshooting: when MVP is not the most valuable parameter.

PMID- 16648074
TI  - How to select patients for atrial fibrillation ablation.

PMID- 16648075
TI  - Cardiac resynchronization therapy in a patient with isolated noncompaction of the
      left ventricle and a narrow QRS complex.

PMID- 16648077
TI  - Intracardiac echocardiography with different approaches for imaging of left
      atrial appendage.

PMID- 16648079
TI  - Epidemiologic study on sudden death in the young composed of 427 deaths
      experienced in 10 years.

PMID- 16648080
TI  - Bioelectricity.

PMID- 16648082
TI  - Shaping medical knowledge II: bias and balance.

PMID- 16648083
TI  - Clinical leadership: developing the role of complementary therapy coordinators.

PMID- 16648084
TI  - A preliminary assessment of the impact of cranial osteopathy for the relief of
      infantile colic.
AB  - In this open, controlled, prospective study, 28 infants with colic were
      randomized to either cranial osteopathic manipulation or no treatment; all were
      seen once weekly for 4 weeks. Treatment was according to individual findings, and
      administered by the same practitioner. Parents recorded time spent crying,
      sleeping and being held/rocked on a 24-hour diary. A progressive, highly
      significant reduction between weeks 1 and 4 in crying (hours/24h) was detected
      (P<0.001) in treated infants; similarly, there was a significant improvement in
      time spent sleeping (P<0.002). By contrast, no significant differences were
      detected in these variables for the control group. Overall decline in crying was
      63% and 23%, respectively, for treated and controls; improvement in sleeping was
      11% and 2%. Treated infants also required less parental attention than the
      untreated group. In conclusion, this preliminary study suggests that cranial
      osteopathic treatment can benefit infants with colic; a larger, double-blind
      study is warranted.

PMID- 16648085
TI  - Redefining the randomized controlled trial in the context of acupuncture
      research.
AB  - BACKGROUND: The randomized controlled trial (RCT) is considered the 'gold
      standard' methodology for evaluating efficacy of an intervention. It has been
      argued that RCTs cannot be used to examine the effectiveness of acupuncture.
      PURPOSE: The purpose of this paper is to examine the applicability of an RCT
      study design for acupuncture research. FINDINGS: RCTs would be more effective in
      studying acupuncture if study participants were randomized to groups based on the
      acupuncture diagnosis and not solely on the Western diagnostic criteria.
      Treatments must also be standardized somewhat to ensure replicability of the
      study and the information it provides. Blinding is not absolutely necessary for a
      good-quality RCT; however, if used, control groups need to be standardized and
      sham techniques evaluated to ensure accurate interpretation of results.
      CONCLUSIONS: With these factors combined, it is possible to greatly increase
      internal and external validity in acupuncture RCTs.

PMID- 16648086
TI  - Effects of abdominal electroacupuncture on parameters related to obesity in obese
      women: a pilot study.
AB  - The aim of this study was to elucidate the effects of electroacupuncture at
      abdominal meridian points on various obesity-related parameters: body weight
      (BW), body fat (BF) percentage, body mass index (BMI), percent ideal body weight
      (PIBW), and waist (WC) and hip (HC) circumferences. All of these parameters
      changed significantly compared to pretreatment in this pilot uncontrolled study
      involving 31 women with obesity. The percent reductions were 5.3% in BW, 1.3% in
      BF, 4.7% in BMI, 6.0% in PIBW, 4.6% in WC, 6.2% in HC, and 2.1% in the WC/HC
      ratio. The most affected variable was WC (effect size=0.58). Since this was a
      pilot study with several limitations, such as a small sample size and absence of
      a control treatment and appropriate follow-up, further studies that include a
      randomized design, larger sample sizes, and more detailed data about the subjects
      are needed to convincingly show the effects of electroacupuncture at abdominal
      meridian points on overweight and obese patients.

PMID- 16648087
TI  - Palpatory diagnosis of plagiocephaly.
AB  - INTRODUCTION: The term plagiocephaly, from the Greek plagios (oblique) and
      kephale (head), means distortion of the head, and refers clinically to cranial
      asymmetry. Cranial Osteopathy, since it was first proposed, has focussed upon the
      diagnosis and treatment of birth trauma and cranial asymmetries, and consequently
      specific therapy for plagiocephalic deformities has been described. Osteopathic
      manipulation also has been proposed as a treatment for torticollis, a condition
      associated with plagiocephaly. For these reasons, we decided to look at the
      mechanics of the occipital bone and the adjacent atlas and bones of the cranial
      base, in relation to functional plagiocephaly. METHODS: The records of 649
      children seen in an osteopathic practice in Lyon, France, were reviewed
      retrospectively, in compliance with the legal requirements of the Commission
      Nationale de l'Informatique et des Libertes (CRIL) and the Helsinki accord, for
      gender, age at presentation, birth history, obstetrical data (breech
      presentation, vacuum extraction, forceps delivery or Caesarean section),
      presenting complaint, side of posterior plagiocephaly, side of frontal
      plagiocephaly, torticollis, motion pattern of the occipital bone upon the atlas,
      and motion pattern of the spheno-occipital synchondrosis. RESULTS: We found
      significant correlations between plagiocephaly (right/left) and primipara
      (P=0.024), use of forceps (P=0.055) and extractor suction (P=0.055). Correlations
      were also found between flattening of the occiput (right/left) and lateral strain
      of the spheno-occipital synchondrosis (P=0.002) and between plagiocephaly
      (right/left) and occipito-atlantal motion (P=0.000). CONCLUSION: We found a
      significant correlation between the lateral strain pattern of the spheno
      occipital synchondrosis and plagiocephaly and between rotational dysfunction of
      the occiput upon the atlas and the side of posterior plagiocephaly. We suggest
      that thorough neonatal osteopathic examination can identify individuals
      predisposed to develop posterior plagiocephaly.

PMID- 16648088
TI  - Tai Chi and older people in the community: a preliminary study.
AB  - This paper outlines a qualitative exploratory study of the individual experiences
      of older people who practise Tai Chi for health. The study aimed to identify
      factors that influence the attraction of Tai Chi for older people. Participants
      were recruited from a selection of Tai Chi clubs in the north of England.
      Participant and non-participant observation of a selection of Tai Chi practice
      sessions was undertaken along with interviews with 7 older people. Findings show
      that individuals who practice Tai Chi report a variety of immediate and lasting
      physical and mental benefits. Being part of a group that both learns and
      practises Tai Chi together appears to be important to the experience and
      awareness of the spiritual nature of Tai Chi was also reported. It is argued that
      older people who practise Tai Chi may have a particular view on ageing, health
      and well-being that the activity of Tai Chi allows them to express and future
      study intends to investigate this in more detail.

PMID- 16648089
TI  - A retrospective cohort study exploring the relationship between antenatal
      reflexology and intranatal outcomes.
AB  - The integration of reflexology into midwifery care has become more common in
      recent years as a result of a developing interest in alternative and
      complementary therapies and also due to the integration of new skills into
      midwifery practice. The objective of this study was to investigate the
      association of antenatal reflexology with different outcomes in the intranatal
      period. The key variables of interest were onset of labour, duration of labour,
      analgesia used and mode of delivery. The findings showed there was no significant
      difference in the onset of labour or duration of labour between the two groups.
      The group who had four or more reflexology treatments had a reduced length of
      labour but this was not statistically significant. There was a significant
      difference in the use of Entonox between the two groups with the reflexology
      group having a lower uptake. Fewer women in the reflexology group had a normal
      labour with a higher percentage of women having a forceps delivery. In conclusion
      the only statistically significant difference between groups was less use of
      Entonox in the reflexology group. Further research requires standardized
      treatment and outcome measurement using prospective randomized designs with large
      samples.

PMID- 16648090
TI  - Complementary therapies in pregnancy: midwives' and obstetricians' appreciation
      of risk.
AB  - Complementary medicine is increasingly being integrated into maternity care,
      primarily by midwives in response to mothers' demands. Midwives and obstetricians
      must, however, develop a comprehensive evidence-based knowledge of risks, as well
      as benefits, to ensure that any complementary therapies in pregnancy and
      childbirth are not only effective but also safe. This paper discusses the results
      of an evaluative audit of midwives' and obstetricians' knowledge of and attitudes
      to complementary therapies in pregnancy in an NHS antenatal clinic which revealed
      a generalised lack of knowledge and poor understanding of the possible risks to
      women.

PMID- 16648091
TI  - Integrated traditional Chinese medicine.
AB  - To experience the integration of traditional Chinese medicine (TCM) in China was
      'the chance of a lifetime; thanks to the support of the Winston Churchill
      Memorial Trust. The scale and range of TCM available in terms of health care
      provision, education and research is unique in the world. This holistic
      integrative medicine is part of Chinese culture. Regulation and training of
      practitioners has similarities with current structures emerging in the UK in
      preparation for the statutory regulation for acupuncture and herbal medicine.
      China's research activity is a critical component of informing the debate on
      evidence-based practice and now real opportunities for collaboration and
      dissemination are beginning to emerge.

PMID- 16648092
TI  - A randomised-controlled trail examining the effects of reflexology of patients
      with chronic obstructive pulmonary disease (COPD).
AB  - It is known that many patients with obstructive pulmonary diseases use a number
      of complementary and alternative medicines (CAM). There has been a great deal of
      interest into the CAM recently, with the House of Lords select committee for
      science and technology's report suggesting randomised-controlled trials are the
      best means of researching the area. There is very little research into the
      effects of reflexology specifically on the effects it has on COPD. As such a
      randomised-controlled trial was set up to examine the effects of reflexology
      treatments on COPD. Results were qualitative and quantitative and showed that
      there are a number of areas of possible benefit for patients with COPD, but a
      larger scale study with a longer time frame is needed for a full evaluation of
      these effects.

PMID- 16648093
TI  - Evaluating the effectiveness of aromatherapy in reducing levels of anxiety in
      palliative care patients: results of a pilot study.
AB  - Results of the pilot study of the four counties randomised controlled trial to
      evaluate the effectiveness of aromatherapy massage with 1% Santalum album
      (Sandalwood) (group A) when compared with massage with Sweet Almond Carrier oil,
      (group B) or Sandalwood oil via an aromastone (group C), in reducing levels of
      anxiety in palliative care. The aims of the pilot study were to evaluate the
      effectiveness of aromatherapy in reducing anxiety in patients receiving
      palliative care in four counties. The primary end points of the research were to
      report a statistically significant difference in anxiety scores between
      experimental group (B) and comparison groups (A and C) and to influence the
      integration of aromatherapy into all aspects of palliative care. The limited data
      of the pilot study (N=34) tested the logistics of the research, particularly the
      25% attrition rate and the robustness of the data collection tools. The results
      were not substantial enough to generate coherent statistics. Therefore no
      assumptions could be drawn from these results due to the inconsistencies that
      were bound to occur in such a small sample. However, the results do seem to
      support the notion that Sandalwood oil is effective in reducing anxiety.

PMID- 16648094
TI  - Coordinating integrated services: a pilot study with participants of a co
      ordinators course.
AB  - The aim of this study was to explore developments in integrative practice in
      cancer care. Views were drawn from a small focus group (n=4), with students from
      a coordinators course. The role of a coordinator or team leader has been
      suggested as pivotal to service integration and organisation [National guidelines
      for the use of complementary therapies in supportive and palliative care. The
      Prince of Wales's foundation for Integrated Health & The National Council for
      Hospice and Specialist Palliative Care Services London POWFIH, 2003; Mackereth,
      European Journal of Oncology Nursing 8 (2004) 1]. The participants suggested that
      there are areas which need to be developed to achieve this goal, including
      evidence based practice, standardisation of training, and ongoing support, and
      personal development.

PMID- 16648095
TI  - The spiritual encounter within a complementary therapy treatment.
AB  - Interest in both spirituality and complementary therapies is growing, with their
      inclusion in both daily life and in health care. The concept of spirituality and
      the delivery of a therapy have a certain synergy as they both espouse a view of
      the world that recognises the importance of the whole person. Increasingly,
      clients want their values and beliefs attended to, perhaps choosing a therapy as
      a pathway to nourish their sense of the spiritual. Consequently working in a
      holistic way the complementary therapist needs to acknowledge the spiritual
      dimension of the client. Integral to this is how the therapeutic encounter
      facilitates this engagement and how important it is that the therapist develops
      and explores their own spirituality and life values. This article is an
      exploration of how spirituality and complementary therapies can legitimately work
      together, creating a sacred space for both therapist and client.

PMID- 16648096
TI  - Bad patients meet good drugs.

PMID- 16648097
TI  - The long and tortuous way towards the remedy.

PMID- 16648098
TI  - Molecular alterations in the pathogenesis of endometrial adenocarcinoma.
      Therapeutic implications.
AB  - Molecular genetic evidence indicates that endometrial carcinoma likely develops
      as the result of a multistep process of oncogene activation and tumor suppressor
      gene inactivation. These molecular alterations appear to be specific for Type I
      (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are
      characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as
      evidenced by the microsatellite instability phenotype, and a near diploid
      karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are
      usually nondiploid. The clinical value of many of these molecular markers is now
      being tested and it may help to refine diagnosis and establish an accurate
      prognosis. Furthermore, some of these tumor biomarkers constitute the targets for
      emerging therapies. Transtuzumab against Her-2/neu and bevacizumab against VEGF
      overexpressing carcinomas are among the promising novel treatments. Additional
      translational research is needed to identify molecular and genetic alterations
      with potential for therapeutic interventions.

PMID- 16648099
TI  - New therapeutic targets in cancer: the epigenetic connection.
AB  - Cancer is an epigenetic disease, a combination of DNA modifications, chromatin
      organization and variations in its associated proteins, configure a new entity
      that regulates gene function throughout methylation, acetylation and chromatin
      remodelling. Irregular de novo DNA methylation, mainly promoter hypermethylation,
      histone deacetylation or methylation are important means for the transcriptional
      repression of cancer-associated genes. Reverse these epigenetic processes
      restoring normal expression of malignancy- preventing-genes has consequently
      become a new therapeutic target in cancer treatment. Aberrant patterns of
      epigenetic modifications will be, in a near future, crucial parameters in cancer
      diagnosis, prognosis and therapy.

PMID- 16648100
TI  - Proteomic analysis in cancer research: potential application in clinical use.
AB  - The ultimate goal of cancer proteomics is to adapt proteomic technologies for
      routine use in clinical laboratories for the purpose of diagnostic and prognostic
      classification of disease states, as well as in evaluating drug toxicity and
      efficacy. The novel technologies allows researchers to facilitate the
      comprehensive analyses of genomes, transcriptomes, and proteomes in health and
      disease. The information that is expected from such technologies may soon exert a
      dramatic change in cancer research and impact dramatically on the care of cancer
      patients. Analysis of tumor-specific proteomic profiles may also allow better
      understanding of tumor development and the identification of novel targets for
      cancer therapy. The localization of gene products, which is often difficult to
      deduce from the sequence, can be determined experimentally. Mechanisms, such as
      regulation of protein function by proteolysis, recycling, and isolation in cell
      compartments, affect gene products, not genes. Finally, protein-protein
      interactions and the molecular composition of cellular structures can be
      determined only at the protein level. The biological variability among patient
      samples as well as the great dynamic range of biomarker concentrations are
      currently the main challenges facing efforts to deduce diagnostic patterns that
      are unique to specific disease states. While several strategies exist to address
      this problem, we have tried to offer a wide perspective about the current
      possibilities.

PMID- 16648101
TI  - Recommendations for treatment with IMRT for prostate and head-neck cancer.
      Axencia de Avaliacion de Tecnoloxias Sanitarias de Galicia.
AB  - Intensity-modulated radiation therapy (IMRT) is an advanced form of radiotherapy
      for the treatment of cancer that allows, on one hand, to administer a more
      homogeneous dose to the patients on the volume to irradiate (which would increase
      the local control of the disease), and on the other hand, to diminish the
      toxicity in the organs at risk. This type of treatment is based on imaging
      techniques, on computer dosimetry programs, and on more precise immobilization
      accessories. Before delivering IMRT it is necessary to establish a protocol that
      includes the different phases of the treatment process, that is, the obtaining of
      anatomical data, beam definition, calculation, dose distribution, and treatment
      performance and control. In this article we present the basic standards for the
      IMRT treatment for prostate and head-neck cancer agreed upon a consensus meeting.
      The follow-up of the recommendations settled down in this document will help in
      the establishment of a standardized clinical practice -assuring the quality- and
      a better evaluation of the results of the clinical intervention.

PMID- 16648102
TI  - Whole brain irradiation and temozolomide based chemotherapy in melanoma brain
      metastases.
AB  - INTRODUCTION: Whole brain irradiation (WBRT) remains a recommended treatment for
      patients with brain metastases from malignant melanoma in terms of symptom
      palliation, especially when extracranial systemic disease is present.
      Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma.
      The objective was to evaluate the potential benefit in survival of two different
      schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10
      fractions) and further TMZ based chemotherapy. MATERIALS AND METHOD: We have
      conducted a retrospective study in a group of twenty-one patients (RTOG Recursive
      Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n =
      11) and 30 Gy/10 fractions (n = 10). All patients received further TMZ based
      chemotherapy administered as a single chemotherapeutic agent or in combination
      with chemo-immunotherapy. RESULTS: Prognostic variables such as: age, Karnofsky
      performance status, extracranial metastases and number of brain metastases, were
      analyzed in both groups of treatment without statistically significant
      differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI
      95%: range 2- 6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0-7
      months) without statistically significant differences (Log rank p = 0.74). There
      was one complete response and two partial responses. CONCLUSIONS: The results
      suggest that MST was not significantly affected by the total dose/fractionation
      schedule.

PMID- 16648103
TI  - Damage assessment in gastric cancer treatment with adjuvant radiochemotherapy:
      calculation of the NTCP's from the differential HDV of the organs at risk.
AB  - OBJECTIVE: To calculate the Normal Tissue Complication Probabilities (NTCP) for
      the liver, right kidney, left kidney and spinal cord, as well as the global
      Uncomplicated Tumour Control Probability (UTCP) in gastric cancer patients who
      underwent a treatment with radiotherapy after radical surgery in our environment.
      MATERIAL AND METHOD: In April 2000, a postoperative chemotherapy (QT-RT) protocol
      started in the province of Malaga for Gastric Adenocarcinomas with postsurgical
      stage II or higher (pT3-4 and/or pN+). This clinical protocol served as a base
      for our NTCP and UTCP retrospective theorical study. A virtual simulation and a
      3D planning were made in all cases. The differential HDV, selected for each
      patient were obtained for the 4 organs at risk (OR). Hystograms reduction was
      made by the Kutcher and Burman's Effective Volume method. NTCP calculations by
      Lyman's models. The following variables were calculated: maximal dose for each
      organ (Dmax), Effective Volume (Veff), TD50 (Veff/Vref); NTCP for each organ of
      the patient; global UTCP for each patient. Differences between the 2 treatment
      techniques were analysed (2-field versus 4-field technique). For the NTCP
      calculations the computer application Albireo 1.0(R) was used. RESULTS: 29
      patients to assess with an average age of 54 +/- 10 years (range: 38-71); 65.5%
      men/34.5% women. The technique used was the field technique AP-PA in the 51.7%
      (15) and with 4 fields in 48.3% (14) of the cases. The global damage is estimated
      in 16% with a range between 0 and 37%. This goes up to 25% with the 2-field
      technique, with a wide range between 2 and 48% and it remains reduced to 4%,
      within a range between 0 and 12% when 4 fields are used. There were significant
      differences concerning the estimated damage probability (NTCP) on liver, spinal
      cord and left kidney, depending on the use of two or four fields. CONCLUSION:
      NTCP and the global UTCP values of the organs at risk allow to compare a
      technique net benefit from another in each particular case, although in our
      theoretical study the comparison was done among the patients. It is important to
      stress that the calculations of the TCP and NTCP have a limited quantitative
      signification but they are useful and beneficial in order to decide between
      treatment plans when they are supported by the clinical knowledge.

PMID- 16648104
TI  - Absorbed dose and transmission factor in blocked fields for radiotherapy
      treatments with 6 MV X-ray.
AB  - Absorbed dose and transmission factors were determined for 6 MV X-ray fields
      applied in four conventional external radiation treatments where protection
      blocks are used to shield organs at risk. Studied treatments are: head and neck
      (cancer of the larynx), breast (breast cancer), brain (brain tumours) and pelvis
      (cervix-uterine cancer). Experimental determinations were made using ionization
      chambers and thermoluminescent dosimeters, at different locations in phantoms,
      for blocked and unblocked fields. Calculated absorbed doses, using the treatment
      planning system and Clarkson method, were compared to those measured. Measured
      transmission factor values ranged from 5% to 18%. It was found that the planning
      treatment system may underestimate the absorbed dose under the blocks, up to 35%.

PMID- 16648105
TI  - Voice quality assessment after laryngeal cancer radiotherapeutic treatment at
      initial stages.
AB  - INTRODUCTION: The voice quality resulting from the radiotherapeutic treatment is
      a relevant factor to take into consideration at the time of evaluating the
      results. In this study the results of an objective assessment in relation to the
      vocal function and the patients' voice self-evaluation are presented. MATERIALS
      AND METHODS: 18 glottic tumour patients, at initial stage, treated with
      radiotherapy, were studied. There were made an objective analysis on the voice
      and a study on the perceived quality both by the examiners and the patients.
      RESULTS: Normal voices were observed in the 11%, slight dysphonias in 44.4%,
      moderate dysphonias in 27.8% and severe dysphonias in 16.7% of the cases.
      Spectrographically, the 18 samples were classified as Grade I one case (5.5%),
      Grade II 7 (38.8%), Grade III 5 (27.7%) and Grade IV 5 (27.7%). The questionnaire
      Voice Handicap Index which was completed by the patients themselves, gave out
      results values very close to normality. CONCLUSIONS: the patients voice acoustic
      analysis of the series shows the damage thereof after the radiotherapeutic
      treatment is minimum as well as the handicap feeling of the T1 laryngeal
      carcinoma patients treated with radiotherapy.

PMID- 16648106
TI  - Mammary hamartoma.
AB  - INTRODUCTION: Mammary hamartomas are rare benign breast lumps. They are usually
      painless, wellcircumscribed, mobile and with no adherence to skin or muscle,
      composed of varying amounts of fat, glandular and fibrous tissue. Mammary
      hamartoma has been classically considered as an underdiagnosed pathology, but
      with the increasing use of diagnostic procedures in breast tumours, the number of
      hamartomas has increased in the last years. Because there is no distinct
      pathological feature, a correlation with the clinical findings and image
      techniques is necessary in order to achieve a correct diagnosis of the pathology.
      MATERIALS AND METHODS: The clinicopathological features of 8 mammary hamartomas
      are reported here. RESULTS: The patients are ranged in age from 34 to 67 years.
      The initial manifestation was in all cases a well-circumscribed, soft, palpable
      breast lump. Mammography was performed in all patients. Other diagnostic
      procedures used in the diagnosis were Ultrasound, Fine Needle Aspiration Cytology
      and Needle Core Biopsy. Treatment was tumorectomy. We describe a case of
      recurrence after excision of the lump in a more aggressive histological form and
      one patient who presented the coexistence of a mammary hamartoma and an invasive
      ductal carcinoma. CONCLUSION: Mammary hamartoma is an uncommon breast tumour. It
      is necessary the correlation between pathology and clinical and radiological
      findings. We express our management plan for these lesions.

PMID- 16648107
TI  - Giant splenic metastasis due to lung adenocarcinoma.
AB  - Lung cancer is the most prevalent malignancy in western countries and most of the
      patients present at advanced stages, but single splenic metastasis is exceptional
      instead. We report on a case of a seventy- three-year old male presenting with
      non-hemoptoic productive cough, constitutional syndrome and pain in the left
      lower quadrant. Physical examination and complementary radiological and
      histological procedures revealed the presence of an adenocarcinoma of the left
      lung with probable splenic metastasis. The patient underwent splenectomy, which
      confirmed the diagnose of splenic metastasis of lung adenocarcinoma and,
      secondly, lung resection was performed. Topics about lung cancer metastasis are
      discussed.

PMID- 16648108
TI  - Intraventricular metastases from rectal-sigmoid adenocarcinoma.
AB  - Secondary cardiac tumours are rare. The new diagnostic technology and more
      effective chemotherapy schedules for primary tumours, leading to a longer
      survival, have increased the frequency of such tumors. Adenocarcinoma accounted
      for around 40% of all metastases to the heart; the most frequently involved sites
      are pericardium and epicardium. We present a patient with an unusual
      intraventricular metastases from adenocarcinoma of rectal-sigmoid origin.

PMID- 16648109
TI  - Solitary metastasis in a nasal fossa as the first manifestation of a renal
      carcinoma.
AB  - Renal cell carcinoma is an uncommon tumor in adults. Metastasis in the nasal
      fossa is rare, and can become apparent as a result of repeated epistaxis. We
      report a patient with renal cell carcinoma presenting with epistaxis secondary to
      a metastasis in the right nasal fossa. The primary tumor was treated with
      nephrectomy and the nasal fossa metastasis was treated successfully with
      embolization, chemoimmunotherapy, surgery, and radiotherapy. The presence of
      repeated epistaxis may very occasionally be the first symptom of renal cell
      carcinoma, and systemic treatment combined with local treatment may enable
      adequate control of the disease.

PMID- 16648110
TI  - To perform or not D2 extended lymphadenectomy in patients with gastric cancer in
      the West. Effectiveness and limits.

PMID- 16648111
TI  - The truths of science.

PMID- 16648112
TI  - Oncopaz cooperative group.

PMID- 16648113
TI  - Molecular biology in prostate cancer.
AB  - Genes involved in cancer generation are usually tumor suppressors and oncogenes.
      Progressive genetic alterations in these genes are involved in the mechanisms of
      tumorigenesis. In prostate cancer, additionally several chromosomal loci that
      should harbor mutated genes have been proposed. Some genes have been found
      altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2),
      CDKN2A and MSR1 and those can be natural targets for new strategies of treatment.
      Besides, gene therapy has been suggested to be suitable for prostate cancer
      treatment. This approach includes ex vivo corrective therapy, suicide, and
      antisense therapy.

PMID- 16648114
TI  - Protein kinases and phosphatases as therapeutic targets in cancer.
AB  - Protein phosphorylation plays key roles in many physiological processes and is
      often deregulated in pathological conditions. Our current understanding of how
      protein kinases and phosphatases orchestrate the phosphorylation changes that
      control cellular functions has made these enzymes potential drug targets for the
      treatment of many diseases. The success of the tyrosine kinase inhibitor Gleevec
      in the treatment of some cancers has further invigorated the development of
      kinase inhibitors as anti-cancer drugs. A large number of these compounds are
      currently undergoing clinical trials and there is much expectation on the
      therapeutic potential of these molecules, as more specific and less toxic drugs
      than currently used generic chemotherapeutic agents. In this manuscript, we
      review the current status of more than 30 protein kinase inhibitors with proven
      or potential therapeutic value for cancer treatment. These include inhibitors of
      receptor and cytosolic tyrosine kinases as well as compounds that target
      different families of serine/threonine kinases involved in signalling and cell
      cycle regulation. We also briefly touch on the prospects of phosphatase
      inhibitors. The combination of kinase inhibitors to target different components
      of signalling pathways that are found deregulated in tumours is also emerging as
      an interesting approach for cancer therapy.

PMID- 16648115
TI  - Genomic platforms for cancer research: potential diagnostic and prognostic
      applications in clinical oncology.
AB  - The completion of the Human Genome Project and the achievement of similar goals
      in other organisms have generated a huge amount of free available information
      with high potential in biomedical sciences. However, the identification of the
      DNA sequence was only a starting point for genomic research. This research has
      been facilitated by the development of new powerful genomic tools that allow the
      use of the wide amount of genomic information generated to address new biological
      and biomedical questions. One of these widely accepted and accessible
      technologies is DNA microarrays. Although the most popular use of DNA microarrays
      is gene expression profiling, due to the continuous advances in microarray
      technologies, scientists have also successfully used them for multiple
      applications, including genotyping, re-sequencing, DNA copy number analysis and
      DNA methylation. In short, DNA microarrays are changing the way cancer research
      scientists are addressing different biological questions and will allow the
      translation of genome research to clinical practice.

PMID- 16648116
TI  - Present state of the Mini-Invasive Surgery (MIS) in esophageal and gastric
      cancer.
AB  - The purpose of this review is to stress the role of the Mini-Invasive Surgery
      (MIS) in the treatment of the esophagogastric malignant illnesses, supporting
      ourselves on the most relevant publications of the literature as well as on our
      own experience in this subject. In short, although no randomised prospective
      study has proven the MIS advantages in relation to the traditional surgery in the
      esophagectomy due to cancer, some authors preferently indicate this approach to
      selected and informed enough patients, who present the following: - High grade
      dysplasia, preferently choosing from laparoscopic transhiatal esophagectomy
      (LTE). - Carcinoma in situ, preferently choosing the LTE vs thoracoscopy. -
      Esophageal tumour locally advanced, in resectable patients with contraindication
      for a thoracotomy or, in initially non-resectable patients with tumoral reduction
      after neo-adjuvant chemo-radiotherapy. The arguments given by the authors are the
      postoperative spectacular improvement in relation to the comfort and quality of
      life and, the absence of oncological negative effects in the long-term followup.
      Concerning gastric cancer, the MIS, as exeresis surgical tool in the so-called
      <<advanced>> gastric forms, is such a definite and oncological approach as the
      traditional approach, and superior to this as far as quality of life is
      concerned. When the MIS is used for treating locally advanced forms of gastric
      cancer, it is as safe as the laparotomic way and it seems to obtain the same
      oncological outcomes in the long-term.

PMID- 16648117
TI  - Oncology care planning. Elements for care quality and management improving.
AB  - BACKGROUND: The improvement of care quality depends on the education and skills
      of the professional team as well as on an adequate work method, which uses the
      right instruments of clinical management such as medical history, registers or
      protocols. OBJECTIVES: Defining standardized criteria related to the oncology
      care quality and applying them to a group of hospitals within the framework of
      continuous improvement establishing comparisons among them. MATERIAL AND METHODS:
      Information taken from 14 Andalusian public hospitals, in 2003 and first semester
      of 2004. A total of 35 variables were collected from official sources, validated
      studies and surveys as a starting point, grouped in four main issues (medical
      history, protocols, central commission and tumour sub-commissions), delays
      (diagnostic, treatment and early diagnostic), variability (cytostatics and
      radiotherapy), research (clinical trials and financed projects) and work loads.
      OUTCOMES: In 3 out of 14 centers medical histories are unique for each patient.
      In average, 3 of the 6 most frequent tumor locations have joint protocols. The
      delays for the diagnostic test vary from 1 to 23 days and from 11 to 29 days for
      treatments. The consumption increase of 12 cytostatics was of 71.8% (average of
      602,413 euro per hospital). The average rate of patients undergoing irradiation
      was of 34 %. 109 clinical trials were approved (a centre performes 26) and 20
      projects were financed (Health Department, Consejeria de Salud). The attendance
      pressure was of 140 patients per specialist in MO and RO (maximum of 241 and 214
      respectively and minimum of 85 and 69). COMMENTS: The information gathered in
      this study shows a diverse nature, and meets items not always taken into
      consideration, in a global way, but with a clearly complementary nature. No
      doubt, they offer a scenery that deepens into the complexity of which today means
      the improvement of the quality of the non-monographic hospital centres that
      attend patients suffering from cancer. It finally offers instruments for the
      improvement of the clinical management which we understand it is of certain
      usefulness.

PMID- 16648118
TI  - Assisted laparoscopic transhiatal esophagectomy for the treatment of esophageal
      cancer.
AB  - BACKGROUND: Esophageal resection for the treatment of esophageal cancer is
      usually associated with high morbido-mortality risks, that can be reduced using
      laparoscopy. Laparoscopic transhiatal esophagectomy (LTE) has the potential to
      improve these results but, to-date, only a few limited series of cases have been
      reported. This report summarizes our experience in 24 cases. OBJECTIVE: To assess
      the outcomes following LTE. METHODS AND MATERIALS: Between 1998 and 2005, LTE was
      performed in 24 patients; 18 men and 6 women with an overall mean age of 63 years
      (range: 36-85). Indication for surgery was lower third esophageal cancer; 11
      squamous cell carcinoma and 13 adenocarcinoma. Neoadjuvant chemotherapy and
      radiotherapy were used in 18 patients (75%). A laparoscopic transhiatal approach
      was used to perform an esophagectomy with curative intent. A cervical
      esophagogastric anastomosis was created. RESULTS: No reversion to conventional
      open surgery was required. Mean anesthesia time was 293.8 min (range: 255-360).
      Major complications occurred in 7 patients (29.2%). Two patients (8.3%) had
      leakage from the cervical anastomosis. Surgical mortality was 8.3%. The median
      stay in Intensive Care Unit was 5 days (range: 1-29). Median hospital stay was
      11.5 days (range: 7-54). At a mean follow-up of 24.9 months, 8 patients (36.4%)
      had disease recurrence (36.4%), global survival rate was 62.5%, and diseasefree
      survival rate was 50%. CONCLUSIONS: Assisted laparoscopic transhiatal
      esophagectomy for lower third esophageal cancer is a potentially safe and
      effective method when performed by surgeons with expertise in the field. Benefits
      from this approach need to be confirmed by further randomized studies.

PMID- 16648119
TI  - Serum endostatin and bFGF as predictive factors in advanced breast cancer
      patients treated with letrozole.
AB  - INTRODUCTION: To investigate the value of baseline serum levels of VEGF, bFGF,
      endostatin and their ratio as predictive factors of response to endocrine therapy
      in patients with metastatic breast cancer (MBC) and positive ER treated with
      letrozole after tamoxifen failure. MATERIALS AND METHOD: The serum levels of
      endostatin, VEGF and bFGF were determined in postmenopausal patients with
      progressing MBC from serum samples obtained before initiation of letrozole. The
      relation between serum angiogenic factor levels and TTP was investigated.
      RESULTS: Seventy-six patients (45.2%) presented a high endostatin level (> 24.6
      ng/ml), 40% low bFGF levels (0 pg/ml) and 50.4% low VEGF (=/< 187 ng/ml). With a
      median follow-up of 22 months, the median TTP was 12.3 months. Median TTP was
      worse in patients with high endostatin concentration as well as in the low bFGF
      group, but was not affected when VEGF was considered. When the two factors were
      combined, the median TTP of patients with endostatin > 24.6 ng/ml and bFGF equal
      0 pg/ml was 9.5 months versus 19.5 months in patients with endostatin =/< 24.6
      ng/ml and bFGF > 0 pg/ml. CONCLUSIONS: The baseline levels of bFGF and endostatin
      are predictive factors of efficacy in patients with MBC treated with letrozole
      and can select groups with different TTP.

PMID- 16648120
TI  - Complementary and alternative medicine (CAM) in Mexican patients with cancer.
AB  - BACKGROUND: Cancer is the second cause of death in Mexico, most cases are
      detected at advanced stages and the use of chemotherapy is frequent. At present,
      more than 300 types of complementary and/or alternative medicine (CAM) treatments
      are known that offer different therapeutic objectives. Many patients use this
      type of treatments. OBJECTIVE: To determine the characteristics of the patients
      that use CAM, to identify the aim of these treatments, the source of information
      and the potential benefits obtained by the patient. PATIENTS AND METHODS: A
      questionnaire was applied from February 20 to March 5, 2004 to non-selected
      patients with cancer in private consultation to determine age, sex, education
      level, work, use of CAM, type and number of used therapies, potential benefits
      and monthly cost. Two groups were formed, A for users and B for non-users of CAM.
      Results between groups were compared and the mentioned variables were correlated
      with the use of alternative medicine. RESULTS: Group A included 37 patients and
      group B included 38, with no difference regarding age, education level, work and
      oncological diagnosis, p > 0.05; a significant trend was found as regards the
      feminine sex, p = 0.07, neoplasm different from breast cancer, p = 0.08 and
      evident association with neoplasm advanced stages, p = 0.02. Most patients used
      between 1 and 3 types of therapies, 97.2%. The most common types of therapies
      were nutritional and spiritual, 54% and 48.6%, respectively. The source was the
      patient's family in 56.4% and the physician in 24.3%. Complementary and
      alternative therapy was considered a success in 57.1%; most of the users
      mentioned benefits (78.6%) deemed as tranquility (46.4%) or improvement of the
      physical condition (46.4%). The average monthly cost was $ 345.5 dollars, with a
      range of $ 13.6 to $ 2,545.5 dollars. CONCLUSIONS: The use of complementary
      and/or alternative therapy is frequent among young women with advanced cancer and
      high level of education. The family participates in the decision of using these
      methods; most users noticed a benefit in their general condition and reported
      tranquility; these patients may be prone to higher incidence of depression and
      anxiety. The effectiveness and safety of this type of treatments remain to be
      determined, as well as the possible interactions with conventional therapy.

PMID- 16648121
TI  - Prevention of irinotecan associated diarrhea by intestinal alkalization. A pilot
      study in gastrointestinal cancer patients.
AB  - AIM AND BACKGROUND: Intestinal alkalization could prevent irinotecan associated
      diarrhea modulating some chemical equilibria between irinotecan metabolites. The
      aim of this study was to evaluate the efficacy of this procedure in advanced
      gastrointestinal cancer patients (GICP). MATERIALS AND METHOD: In this
      prospective study advanced GICP, receiving irinotecan based chemotherapy
      regimens, were well trained to add sodium bicarbonate to the water intake in
      order to accomplish intestinal alkalization. RESULTS: A total of twenty four
      advanced GICP were enrolled. Grade III-IV diarrhea has been observed in four
      patients (16%), some of whom had several risk factors for diarrhea. Only one out
      of seventeen colorectal cancer patients, receiving the irinotecan combination as
      first line therapy, had grade III-IV diarrhea. No side effects of the procedure
      have been appreciated. CONCLUSIONS: Intestinal alkalization may be effective as a
      preventive treatment for irinotecan associated diarrhea in chemotherapy regimens
      used in GICP. This procedure deserves further investigation.

PMID- 16648122
TI  - Video-assisted surgery in gastric cancer.
AB  - INTRODUCTION: The present study presents the initial results of the use of video
      assisted surgery in the curative intent treatment of gastric cancer in a
      specialised unit of esophago-gastric pathology. METHODS: Since December 2002 we
      have substituted laparotomy for video-assisted surgery for the surgical treatment
      of gastric cancer. We report our initial experience in 28 patients. In 20 we
      performed a total gastrectomy with Roux Y esophago-jejunum reconstruction. In
      another 8 cases we performed subtotal gastrectomy with Roux Y reconstruction. The
      anastomoses in total gastrectomy were performed with laparoscopy with the EEA
      head descending via the endo-esophageal route. The resected piece is extracted
      via minimum laparotomy. The associated complete lympadenectomy D2 was performed
      in the tumours of the gastric antrum and D1 plus the lymph node groups 7, 8, 9
      and proximal 11 at the second level in the gastric body and fundus. RESULTS: The
      mean duration of intervention was 222 minutes and the mean blood loss was 185 ml.
      Mortality was 3.7% and morbidity was 19%. There was a reduction in post-operative
      analgesia requirements and the mean hospital stay was 11 days. CONCLUSIONS:
      Gastric resection and related lympadenectomy can be performed using video
      assisted surgery in a manner that is as safe as conventional surgery and,
      further, has considerable advantages. The greater complexity requires that the
      surgical team is better trained in the use of the laparoscopy technique. In the
      few studies on the theme, there appears to be no oncological inconveniences
      associated with the technique.

PMID- 16648123
TI  - Popliteal lymphadenectomy on sentinel lymph node melanoma metastasis.
AB  - Popliteal lymph node dissection is a procedure that surgeons rarely perform and,
      therefore, scarcely represented in bibliography. In this paper we present the
      case of a patient with melanoma metastasis to popliteal sentinel lymph nodes
      showing the surgical procedure and discussing some epidemiological and technical
      issues.

PMID- 16648124
TI  - Primary bone lymphoma.
AB  - Primary bone lymphoma is a rare condition which represents a low percentage of
      both the malignant primary bone tumours and the non-Hodgkin extranodal lymphoma.
      This explains the lack of publications, lines of investigations, and specific
      diagnostic and treatment protocols. In the following article we will carry out a
      revision of the existing literature on this rare subject, using as argument a
      clinical case of left femoral location stage IE treated with CHOP chemotherapy
      and radiotherapy.

PMID- 16648132
TI  - National survey of British public's views on use of identifiable medical data by
      the National Cancer Registry.
AB  - OBJECTIVES: To describe the views of the British public on the use of personal
      medical data by the National Cancer Registry without individual consent, and to
      assess the relative importance attached by the public to personal privacy in
      relation to public health uses of identifiable health data. DESIGN: Cross
      sectional, face to face interview survey. SETTING: England, Wales, and Scotland.
      PARTICIPANTS: 2872 respondents, 97% of those who took part in the Office for
      National Statistics' omnibus survey, a national multistage probability sample, in
      March and April 2005 (response rates 62% and 69%, respectively). RESULTS: 72%
      (95% confidence interval 70% to 74%) of all respondents did not consider any of
      the following to be an invasion of their privacy by the National Cancer Registry:
      inclusion of postcode, inclusion of name and address, and the receipt of a letter
      inviting them to a research study on the basis of inclusion in the registry. Only
      2% (2% to 3%) of the sample considered all of these to amount to an invasion of
      privacy. Logistic regression analysis showed that the proportions not concerned
      about invasion of privacy varied significantly by country, ethnicity,
      socioeconomic status, and housing tenure, although in all subgroups examined most
      respondents had no concerns. 81% (79% to 83%) of all respondents said that they
      would support a law making cancer registration statutory. CONCLUSIONS: Most of
      the British public considers the confidential use of personal, identifiable
      patient information by the National Cancer Registry for the purposes of public
      health research and surveillance not to be an invasion of privacy.

PMID- 16648133
TI  - Cerebral emboli as a potential cause of Alzheimer's disease and vascular
      dementia: case-control study.
AB  - OBJECTIVE: To compare the occurrence of spontaneous cerebral emboli and venous to
      arterial circulation shunts in patients with Alzheimer's disease or vascular
      dementia and controls without dementia. DESIGN: Cross sectional case-control
      study. SETTING: Secondary care old age psychiatry services, Manchester.
      PARTICIPANTS: 170 patients with dementia (85 with Alzheimer's disease, 85 with
      vascular dementia) and 150 age and sex matched controls. Patients on
      anticoagulant treatment, patients with severe dementia, and controls with marked
      cognitive impairment were excluded. MAIN OUTCOME MEASURES: Frequencies of
      detection of spontaneous cerebral emboli during one hour monitoring of the middle
      cerebral arteries with transcranial Doppler and venous to arterial circulation
      shunts by a transcranial Doppler technique using intravenous microbubbles as an
      ultrasound contrast. RESULTS: Spontaneous cerebral emboli were detected in 32
      (40%) of patients with Alzheimer's disease and 31 (37%) of those with vascular
      dementia compared with just 12 each (15% and 14%) of their controls, giving
      significant odds ratios adjusted for vascular risk factors of 2.70 (95%
      confidence interval 1.18 to 6.21) for Alzheimer's disease and 5.36 (1.24 to
      23.18) for vascular dementia. These spontaneous cerebral emboli were not caused
      by carotid disease, which was equally frequent in dementia patients and their
      controls. A venous to arterial circulation shunt indicative of patent foramen
      ovale was found in 27 (32%) Alzheimer's disease patients and 25 (29%) vascular
      dementia patients compared with 19 (22%) and 17 (20%) controls, giving non
      significant odds ratios of 1.57 (0.80 to 3.07) and 1.67 (0.81 to 3.41).
      CONCLUSION: Spontaneous cerebral emboli were significantly associated with both
      Alzheimer's disease and vascular dementia. They may represent a potentially
      preventable or treatable cause of dementia.

PMID- 16648134
TI  - Inhibiting bacterial fatty acid synthesis.
AB  - The type II fatty acid synthase consists of a series of individual enzymes, each
      encoded by a separate gene, that catalyze discrete steps in chain elongation. The
      formation of fatty acids is vital to bacteria, and each of the essential enzymes
      and their acyl group carriers represent a potential target for the development of
      novel antibacterial therapeutics. High resolution x-ray and/or NMR structures of
      representative members of every enzyme in the type II pathway are now available,
      and these structures are a valuable resource to guide antibacterial drug
      discovery. The role of each enzyme in regulating pathway activity and the
      diversity in the components of the pathway in the major human pathogens are
      important considerations in deciding the most suitable targets for future drug
      development.

PMID- 16648135
TI  - Theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6
      helix bundle formation.
AB  - Retrocyclin-1, a -defensin, protects target cells from human immunodeficiency
      virus, type 1 (HIV-1) by preventing viral entry. To delineate its mechanism, we
      conducted fusion assays between susceptible target cells and effector cells that
      expressed HIV-1 Env. Retrocyclin-1 (4 microm) completely blocked fusion mediated
      by HIV-1 Envs that used CXCR4 or CCR5 but had little effect on cell fusion
      mediated by HIV-2 and simian immunodeficiency virus Envs. Retrocyclin-1 inhibited
      HIV-1 Env-mediated fusion without impairing the lateral mobility of CD4, and it
      inhibited the fusion of CD4-deficient cells with cells bearing CD4-independent
      HIV-1 Env. Thus, it could act without cross-linking membrane proteins or
      inhibiting gp120-CD4 interactions. Retrocyclin-1 acted late in the HIV-1 Env
      fusion cascade but prior to 6-helix bundle formation. Surface plasmon resonance
      experiments revealed that retrocyclin bound the ectodomain of gp41 with high
      affinity in a glycan-independent manner and that it bound selectively to the gp41
      C-terminal heptad repeat. Native-PAGE, enzyme-linked immunosorbent assay, and CD
      spectroscopic analyses all revealed that retrocyclin-1 prevented 6-helix bundle
      formation. This mode of action, although novel for an innate effector molecule,
      resembles the mechanism of peptidic entry inhibitors based on portions of the
      gp41 sequence.

PMID- 16648136
TI  - APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination
      independent mechanism.
AB  - The most common transposable genetic element in humans, long interspersed element
      1 (L1), constitutes about 20% of the genome. The activity of L1 and related
      transposons such as Alu elements causes disease and contributes to speciation.
      Little is known about the cellular mechanisms that control their spread. We show
      that expression of human APOBEC3B or APOBEC3F decreased the rate of L1
      retrotransposition by 5-10-fold. Expression of two related proteins, APOBEC3D or
      APOBEC3G, had little effect. The mechanism of L1 inhibition did not correlate
      with an obvious subcellular protein distribution as APOBEC3B appeared
      predominantly nuclear and APOBEC3F was mostly cytosolic. Two lines of evidence
      indicated that these APOBEC3 proteins use a deamination-independent mechanism to
      inhibit L1. First, a catalytically inactive APOBEC3B mutant maintained L1
      inhibition activity. Second, cDNA strand-specific C --> T hypermutations were not
      detected among L1 elements that had replicated in the presence of APOBEC3B or
      APOBEC3F. In addition, lower levels of retrotransposed L1 DNA accumulated in the
      presence of APOBEC3B and APOBEC3F. Together, these data combined to suggest a
      model in which APOBEC3B or APOBEC3F provide a preintegration barrier to L1
      retrotransposition. A particularly high level of APOBEC3F protein in human testes
      and an inverse correlation between L1 activity and APOBEC3 gene number suggest
      the relevance of this mechanism to mammals.

PMID- 16648137
TI  - Novel mutants of the human beta1-adrenergic receptor reveal amino acids relevant
      for receptor activation.
AB  - Activation of G protein-coupled receptors like the beta(1)-adrenergic receptor
      results in conformational changes that ultimately lead to signal propagation
      through a G protein to an effector like adenylyl cyclase. In this study we
      identified amino acids that seem to be critical for activation of the human
      beta(1)-adrenergic receptor. Activation patterns of mutant receptors were
      analyzed using two structurally different ligands for beta-adrenergic receptors
      that both are mixed agonist/antagonists. Broxaterol and terbutaline are agonists
      at beta(2)- and beta(3)-receptors; however, they act as antagonists at the
      beta(1)-subtype. We reasoned that this functional selectivity may be reflected by
      a corresponding sequence pattern in the receptor subtypes. Therefore, we
      exchanged single amino acids of the beta(1)-adrenergic receptor for residues that
      were identical in the beta(2)- and beta(3)-subtypes but different in the beta(1)
      receptor. Pharmacological characterization of such receptor mutants revealed that
      binding of a panel of agonists and antagonists including broxaterol and
      terbutaline was unaltered. However, two of the mutants (I185V and D212N) were
      activated by broxaterol and terbutaline, which acted as antagonists at the wild
      type receptor. Two additional mutants (V120L and K253R) could be activated by
      terbutaline alone, which is structurally more closely related to endogenous
      catecholamines like epinephrine than to broxaterol. A model of the human beta(1)
      adrenergic receptor showed that the four gain-of-function mutations are outside
      of the putative ligand-binding domain substantiating the lack of an effect of the
      mutations on binding characteristics. These results support the notion that Val
      120, Ile-185, Asp-212, and Lys-253 are critically involved in conformational
      changes occurring during receptor activation.

PMID- 16648138
TI  - Mitogenic responses of vascular smooth muscle cells to lipid peroxidation-derived
      aldehyde 4-hydroxy-trans-2-nonenal (HNE): role of aldose reductase-catalyzed
      reduction of the HNE-glutathione conjugates in regulating cell growth.
AB  - Products of lipid peroxidation such as 4-hydroxy-trans-2-nonenal (HNE) trigger
      multiple signaling cascades that variably affect cell growth, differentiation,
      and apoptosis. Because glutathiolation is a significant metabolic fate of these
      aldehydes, we tested the possibility that the bioactivity of HNE depends upon its
      conjugation with glutathione. Addition of HNE or the cell-permeable esters of
      glutathionyl-4-hydroxynonenal (GS-HNE) or glutathionyl-1,4-dihydroxynonene (GS
      DHN) to cultures of rat aortic smooth muscle cells stimulated protein kinase C,
      NF-kappaB, and AP-1, and increased cell growth. The mitogenic effects of HNE, but
      not GS-HNE or GS-DHN, were abolished by glutathione depletion. Pharmacological
      inhibition or antisense ablation of aldose reductase (which catalyzes the
      reduction of GS-HNE to GS-DHN) prevented protein kinase C, NF-kappaB, and AP-1
      stimulation and the increase in cell growth caused by HNE and GS-HNE, but not GS
      DHN. The growth stimulating effect of GS-DHN was enhanced in cells treated with
      antibodies directed against the glutathione conjugate transporters RLIP76 (Ral
      binding protein) or the multidrug resistance protein-2. Overexpression of RLIP76
      abolished the mitogenic effects of HNE and its glutathione conjugates, whereas
      ablation of RLIP76 using RNA interference promoted the mitogenic effects.
      Collectively, our findings suggest that the mitogenic effects of HNE are mediated
      by its glutathione conjugate, which has to be reduced by aldose reductase to
      stimulate cell growth. These results raise the possibility that the glutathione
      conjugates of lipid peroxidation products are novel mediators of cell signaling
      and growth.

PMID- 16648139
TI  - Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in
      neurons and astrocytes.
AB  - AtT-20 cells expressing the wild-type kappa opioid receptor (KOR) increased
      phospho-p38 MAPK following treatment with the kappa agonist U50,488. The increase
      was blocked by the kappa antagonist norbinaltorphimine and not evident in
      untransfected cells. In contrast, U50,488 treatment of AtT-20 cells expressing
      KOR having alanine substituted for serine-369 (KSA) did not increase phospho-p38.
      Phosphorylation of serine 369 in the KOR carboxyl terminus by G-protein receptor
      kinase 3 (GRK3) was previously shown to be required for receptor desensitization,
      and the results suggest that p38 MAPK activation by KOR may require arrestin
      recruitment. This hypothesis was tested by transfecting arrestin3-(R170E), a
      dominant positive form of arrestin that does not require receptor phosphorylation
      for activation. AtT-20 cells expressing both KSA and arrestin3-(R170E) responded
      to U50,488 treatment with an increase in phospho-p38 consistent with the
      hypothesis. Primary cultured astrocytes (glial fibrillary acidic protein
      positive) and neurons (gamma-aminobutyric acid-positive) isolated from mouse
      striata also responded to U50,488 by increasing phospho-p38 immunolabeling. p38
      activation was not evident in either striatal astrocytes or neurons isolated from
      KOR knock-out mice or GRK3 knock-out mice. Astrocytes pretreated with small
      interfering RNA for arrestin3 were also unable to activate p38 in response to
      U50,488 treatment. Furthermore, in striatal neurons, the kappa-mediated phospho
      p38 labeling was colocalized with arrestin3. These findings suggest that KOR may
      activate p38 MAPK in brain by a GRK3 and arrestin-dependent mechanism.

PMID- 16648140
TI  - Defective human leukocyte antigen class I-associated antigen presentation caused
      by a novel beta2-microglobulin loss-of-function in melanoma cells.
AB  - The major histocompatibility complex class I molecules consist of three subunits,
      the 45-kDa heavy chain, the 12-kDa beta(2)-microglobulin (beta(2)m), and an
      approximately 8-9-residue antigenic peptide. Without beta(2)m, the major
      histocompatibility complex class I molecules cannot assemble, thereby abolishing
      their transport to the cell membrane and the subsequent recognition by antigen
      specific T cells. Here we report a case of defective antigen presentation caused
      by the expression of a beta(2)m with a Cys-to-Trp substitution at position 25
      (beta(2)m(C25W)). This substitution causes misfolding and degradation of
      beta(2)m(C25W) but does not result in complete lack of human leukocyte antigen
      (HLA) class I molecule expression on the surface of melanoma VMM5B cells. Despite
      HLA class I expression, VMM5B cells are not recognized by HLA class I-restricted,
      melanoma antigen-specific cytotoxic T lymphocytes even following loading with
      exogenous peptides or transduction with melanoma antigen-expressing viruses.
      Lysis of VMM5B cells is restored only following reconstitution with exogenous or
      endogenous wild-type beta(2)m protein. Together, our results indicate impairment
      of antigenic peptide presentation because of a dysfunctional beta(2)m and provide
      a mechanism for the lack of close association between HLA class I expression and
      susceptibility of tumor cells to cytotoxic T lymphocytes-mediated lysis in
      malignant diseases.

PMID- 16648141
TI  - Na+/H+ exchanger NHE3 activity and trafficking are lipid Raft-dependent.
AB  - A previous study showed that approximately 25-50% of rabbit ileal brush border
      (BB) Na(+)/H(+) exchanger NHE3 is in lipid rafts (LR) (Li, X., Galli, T., Leu,
      S., Wade, J. B., Weinman E. J., Leung, G., Cheong, A., Louvard, D., and Donowitz,
      M. (2001) J. Physiol. (Lond.) 537, 537-552). Here, we examined the role of LR in
      NHE3 transport activity using a simpler system: opossum kidney (OK) cells (a
      renal proximal tubule epithelial cell line) containing NHE3. approximately 50% of
      surface (biotinylated) NHE3 in OK cells distributed in LR by density gradient
      centrifugation. Disruption of LR with methyl-beta-cyclodextrin (MbetaCD)
      decreased NHE3 activity and increased K'(H+)(i), but K(m)((Na+)) was not
      affected. The MbetaCD effect was completely reversed by repletion of cholesterol,
      but not by an inactive analog of cholesterol (cholestane-3beta,5alpha,6beta
      triol). The MbetaCD effect was specific for NHE3 activity because it did not
      alter Na(+)-dependent l-Ala uptake. MbetaCD did not alter OK cell BB topology and
      did not change the surface amount of NHE3, but greatly reduced the rate of NHE3
      endocytosis. The effects of inhibiting phosphatidylinositol 3-kinase and of
      MbetaCD on NHE3 activity were not additive, indicating a common inhibitory
      mechanism. In contrast, 8-bromo-cAMP and MbetaCD inhibition of NHE3 was additive,
      indicating different mechanisms for inhibition of NHE3 activity. Approximately
      50% of BB NHE3 and only approximately 11% of intracellular NHE3 in polarized OK
      cells were in LR. In summary, the BB pool of NHE3 in LR is functionally active
      because MbetaCD treatment decreased NHE3 basal activity. The LR pool is necessary
      for multiple kinetic aspects of normal NHE3 activity, including V(max) and
      K'(H+)(i), and also for multiple aspects of NHE3 trafficking, including at least
      basal endocytosis and phosphatidylinositol 3-kinase-dependent basal exocytosis.
      Because the C-terminal domain of NHE3 is necessary for its regulation and because
      the changes in NHE3 kinetics with MbetaCD resemble those with second messenger
      regulation of NHE3, these results suggest that the NHE3 C terminus may be
      involved in the MbetaCD sensitivity of NHE3.

PMID- 16648142
TI  - Neurofibroma-associated growth factors activate a distinct signaling network to
      alter the function of neurofibromin-deficient endothelial cells.
AB  - Genetic inactivation of tumor suppressor genes initiates human cancers. However,
      interaction of accessory cells with the tumor-initiating cell within the
      microenvironment is often required for tumor progression. This paradigm is
      relevant to understanding neurofibroma development in neurofibromatosis type I
      patients. Somatic inactivation of the Nf1 tumor suppressor gene, which encodes
      neurofibromin, is necessary but not sufficient to initiate neurofibroma
      development. In contrast, neurofibromas occur with high penetrance in mice in
      which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant
      (Nf1+/-) microenvironment. Neurofibromas are highly vascularized, and recent
      studies suggest that Nf1+/- mice have increased angiogenesis in vivo. However,
      the function of neurofibromin in human endothelial cells (ECs) and the
      biochemical mechanism by which neurofibromin regulates neoangiogenesis are not
      known. Utilizing Nf1+/- mice, primary human ECs and endothelial progenitor cells
      harvested from NF1 patients, we identified a discrete Ras effector pathway, which
      alters the proliferation and migration of neurofibromin-deficient ECs in response
      to neurofibroma-derived growth factors both in vitro and in vivo. Thus, these
      studies identify a unique biochemical pathway in Nf1+/- ECs as a potential
      therapeutic target in the neurofibroma microenvironment.

PMID- 16648143
TI  - Intake of polyunsaturated fatty acids and vitamin E reduces the risk of
      developing amyotrophic lateral sclerosis.
AB  - BACKGROUND: To assess whether the premorbid dietary intake of fatty acids,
      cholesterol, glutamate or antioxidants was associated with the risk of developing
      amyotrophic lateral sclerosis (ALS). METHODS: Patients referred to our clinic
      during 2001-2002, who had definite, probable or possible ALS according to El
      Escorial criteria, without a familial history of ALS, were asked to participate
      in a case-control study (132 patients and 220 healthy controls). A food-frequency
      questionnaire was used to assess dietary intake for the nutrients of interest.
      Multivariate logistic regression analysis was performed with adjustment for
      confounding factors (sex, age, level of education, energy intake, body mass index
      and smoking). RESULTS: A high intake of polyunsaturated fatty acid (PUFA) and
      vitamin E was significantly associated with a reduced risk of developing ALS
      (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p =
      0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E
      appeared to act synergistically, because in a combined analysis the trend OR for
      vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA
      from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03).
      The intake of flavonols, lycopene, vitamin C, vitamin B2, glutamate, calcium or
      phytoestrogens was not associated with the risk of developing ALS. CONCLUSION: A
      high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of
      developing ALS, and these nutrients appear to act synergistically.

PMID- 16648144
TI  - The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to
      cerebral aneurysms.
AB  - BACKGROUND AND AIMS: An important part is played by inflammation in intracranial
      aneurysm formation. The hypothesis that there is an association of the
      proinflammatory cytokine interleukin-6 (IL-6) genotypes (-572G>C and -174G>C)
      with intracranial aneurysms was tested. METHODS: IL-6 genotypes were determined
      in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK
      controls. RESULTS: For both polymorphisms, the distribution of the genotypes and
      estimated allele frequency were different between the control group and the
      aneurysm group. For -572G>C, a higher frequency of the C allele (p = 0.001) and
      more people homozygous for the C allele were found among those with aneurysms
      than among the controls (4.4% v 0.3%, p = 0.001). For -174G>C, more people
      homozygous for the C allele were found among the controls than among those with
      aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an
      increased risk of aneurysms, with the relative risk compared with the common
      haplotype being 1.89 and that for the -572G/174C haplotype being 0.58 (p<0.0005).
      CONCLUSION: This is the first study to show that IL-6 promoter polymorphisms are
      associated with intracranial aneurysmal disease. Whether this association is with
      the development, progression or rupture of such aneurysms, or represents survivor
      bias, is unclear.

PMID- 16648145
TI  - Bifurcations of an epidemic model with non-linear incidence and infection
      dependent removal rate.
AB  - An epidemic model with a generalized non-linear incidence is extended to
      incorporate the effect of an infection-dependent removal strategy, which is
      defined as a function of the number of infected individuals. It is assumed that
      the removal rate decreases from a maximum capacity for removing infected
      individuals as their number increases. The existence and stability of the
      associated equilibria are analysed, and the basic reproductive number (R0) is
      formulated. It is shown that R0 is independent of the functional form of the
      incidence, but depends on the removal rate. Normal forms are derived to show the
      different types of bifurcation the model undergoes, including transcritical,
      generalized Hopf (Bautin), saddle-node and Bogdanov-Takens. A degenerate Hopf
      bifurcation at the Bautin point, where the first Lyapunov coefficient vanishes,
      is discussed. Sotomayor's theorem is applied to establish a saddle-node
      bifurcation at the turning point of backward bifurcation. The Bogdanov-Takens
      normal form is derived, from which the local bifurcation curve for a family of
      homoclinic orbits is formulated. Bifurcation diagrams and numerical simulations,
      using parameter values estimated for some infectious diseases, are also presented
      to provide more intuition to the theoretical findings. The results show that
      sufficiently increasing the removal rate can reduce R0 below a subthreshold
      domain, which leads to disease eradication.

PMID- 16648146
TI  - Mathematical modelling of the loss of tissue compression responsiveness and its
      role in solid tumour development.
AB  - This paper presents a mathematical model of normal and abnormal tissue growth.
      The modelling focuses on the potential role that stress responsiveness may play
      in causing proliferative disorders which are at the basis of the development of
      avascular tumours. In particular, we study how an incorrect sensing of its
      compression state by a cell population can represent a clonal advantage and can
      generate hyperplasia and tumour growth with well-known characteristics such as
      compression of the tissue, structural changes in the extracellular matrix, change
      in the percentage of cell type (normal or abnormal), extracellular matrix and
      extracellular liquid. A spatially independent description of the phenomenon is
      given initially by a system of non-linear ordinary differential equations which
      is explicitly solved in some cases of biological interest showing a first phase
      in which some abnormal cells simply replace the normal ones, a second phase in
      which the hyper-proliferation of the abnormal cells causes a progressive
      compression within the tissue itself and a third phase in which the tissue
      reaches a compressed state, which presses on the surrounding environment. A
      travelling wave analysis is also performed which gives an estimate of the
      velocity of the growing mass.

PMID- 16648147
TI  - Crack/cocaine use in a rural county of England.
AB  - Crack/cocaine use is an increasing problem in the UK. This study is the first to
      ascertain the magnitude of the crack/cocaine problem in a rural county of the UK
      and to determine users' needs for treatment services. A questionnaire on drug
      dependence and risk behaviour was completed by 306 users of drug treatment
      services, and focus groups were conducted with 45 self-selected crack/cocaine
      users. It is estimated that 31% (95% C.I., 26% to 37%) of drug users in treatment
      services have moderate/severe dependence on crack/cocaine. Factors associated
      with severe crack/cocaine dependence are severe dependence on benzodiazepines,
      increasing number of drugs used, engaging in sex work and non-white ethnicity.
      Those with severe dependence have a higher prevalence of hepatitis B and C
      compared with those with moderate or no dependence. All focus group participants
      describe a frenzied drug life so when entering treatment they require additional
      support to give structure to their lives to prevent relapse. Current service
      provision appears not to provide help to crack/cocaine users. Given the lack of
      pharmacological treatment, programmes should incorporate a wide range of
      activities and interventions to provide structure to clients' lives. Learning
      from ex-users was perceived as an important component of treatment.

PMID- 16648148
TI  - The prevalence of problem drug misuse in a rural county of England.
AB  - Previous capture-recapture studies have estimated the prevalence of problem drug
      misuse in urban areas. This study estimates the prevalence in a rural county,
      Norfolk, using data from four sources: drug treatment agencies, probation, the
      arrest referral service, and police (drug-related crime with/without acquisitive
      crime). Careful consideration was given to methods of matching datasets and
      sensitivity analyses involved altering matching rules and postcode criteria.
      Whilst it is recognised that acquisitive crime is often related to drug use, this
      is the first capture-recapture study to incorporate acquisitive crime data. In
      further sensitivity analyses the proportion of acquisitive crime assumed to be
      drug-related was varied from 25-60%. The main analysis provided an estimated
      prevalence of problem drug use in Norfolk of 2.05% (95% confidence interval:
      1.66%-2.56%) for ages 15-54 years, considerably higher than the 1.1% currently
      suggested for the UK. Sensitivity analyses based on varied matching and postcode
      criteria produced estimates ranging from 2.41%-3.37%, suggesting our estimate may
      be conservative. Sensitivity analyses assuming that 25-60% of acquisitive crimes
      were drug-related, produced estimates ranging from 2.02% to 5.73%, further
      supporting our main analysis. In conclusion, this study provides evidence that
      problem drug misuse is more prevalent in this rural population than previously
      thought.

PMID- 16648149
TI  - Occurrence and outcome of delirium in medical in-patients: a systematic
      literature review.
AB  - BACKGROUND: Despite the acknowledged clinical importance of delirium, research
      evidence for measures to improve its management is sparse. A necessary first step
      to devising appropriate strategies is to understand how common it is and what its
      outcomes are in any particular setting. OBJECTIVE: To determine the occurrence of
      delirium and its outcomes in medical in-patients, through a systematic review of
      the literature. METHOD: We searched electronic medical databases, the
      Consultation-Liaison Literature Database and reference lists and bibliographies
      for potentially relevant studies. Studies were selected, quality assessed and
      data extracted according to preset protocols. RESULTS: Results for the occurrence
      of delirium in medical in-patients were available for 42 cohorts. Prevalence of
      delirium at admission ranged from 10 to 31%, incidence of new delirium per
      admission ranged from 3 to 29% and occurrence rate per admission varied between
      11 and 42%. Results for outcomes were available for 19 study cohorts. Delirium
      was associated with increased mortality at discharge and at 12 months, increased
      length of hospital stay (LOS) and institutionalisation. A significant proportion
      of patients had persistent symptoms of delirium at discharge and at 6 and 12
      months. CONCLUSION: Delirium is common in medical in-patients and has serious
      adverse effects on mortality, functional outcomes, LOS and institutionalisation.
      The development of appropriate strategies to improve its management should be a
      clinical and research priority. As delirium prevalent at hospital admission is a
      significant problem, research is also needed into preventative measures that
      could be applied in community settings.

PMID- 16648150
TI  - Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human
      fetuses and adults.
AB  - The signals initiating the growth of primordial follicles are unknown. Growth
      factors such as neurotrophin 4/5 (NT-4/5) and brain-derived neurotrophic factor
      (BDNF) may play a role in this process. To investigate the expression of NT-4/5
      and BDNF and their receptor tyrosine kinase B (TrkB) in the early developing
      follicles, we fixed and froze 12 ovarian samples from adolescents/adults and 31
      ovaries from human fetuses. The fixed samples were prepared for
      immunohistochemical staining for NT-4/5, BDNF and the TrkB receptor. Total RNA
      was extracted from the frozen ovarian samples, and the expression of NT-4/5, BDNF
      and the TrkB receptor (full length and two truncated isoforms) was investigated
      by RT-PCR. Products were resolved by 1% agarose gel electrophoresis and image
      analysis. Immunohistochemical staining revealed the expression of NT-4/5 and BDNF
      mainly in oocytes and, in a minority of samples, also in the granulosa cells
      (GCs); TrkB receptor was identified in oocytes and GCs. Transcripts of NT-4/5,
      BDNF and all forms of TrkB receptor were identified in the samples. To elucidate
      whether indeed NT-4/5 and BDNF are involved in growth initiation of human
      primordial follicles, they should be added to the culture medium.

PMID- 16648151
TI  - Expression and regulation of vascular endothelial growth factor ligands and
      receptors during menstruation and post-menstrual repair of human endometrium.
AB  - Regeneration and growth of the human endometrium after shedding of the functional
      layer during menstruation depends on an adequate angiogenic response. We analysed
      the mRNA expression levels of all known vascular endothelial growth factor (VEGF)
      ligands and receptors in human endometrium collected in the menstrual and
      proliferative phases of the menstrual cycle. In addition, we evaluated the
      expression of VEGF-A, VEGF-R2 and NRP-1 at the protein level. Two periods of
      elevated mRNA expression of ligands and receptors were observed, separated by a
      distinct drop at cycle days (CDs) 9 and 10. Immunohistochemical staining showed
      that VEGF and VEGF-R2 were expressed in epithelial, stromal and endothelial
      cells. NRP-1 was mainly confined to stroma and blood vessels; only in late
      proliferative endometrium, epithelial staining was also observed. Except for
      endothelial VEGF-R2 expression in CDs 6-8, there were no significant differences
      in the expression of VEGF, VEGF-R2 or NRP-1 in any of the cell compartments. In
      contrast, VEGF release by cultured human endometrium explants decreased during
      the proliferative phase. This output was significantly reduced in menstrual and
      early-proliferative endometrium by estradiol (E2) treatment. Western blot
      analysis indicated that part of the VEGF-A was trapped in the extracellular
      matrix (ECM). Changes in VEGF ligands and receptors were associated with elevated
      expression of the hypoxia markers HIF1alpha and CA-IX in the menstrual and early
      proliferative phases. HIF1alpha was also detected in late-proliferative phase
      endometrium. Our findings indicate that VEGF-A exerts its actions mostly during
      the first half of the proliferative phase. Furthermore, VEGF-A production appears
      to be triggered by hypoxia in the menstrual phase and subsequently suppressed by
      estrogen during the late proliferative phase.

PMID- 16648152
TI  - Prospective comparison of sevoflurane and desflurane in formerly premature
      infants undergoing inguinal herniotomy.
AB  - BACKGROUND: Formerly premature infants having inguinal herniotomy have been at a
      high risk of postoperative apnoea, newer less soluble anaesthetic agents may
      reduce this risk. METHODS: Thirty infants, under 37 weeks gestation and under 47
      weeks post-conceptional age, undergoing inguinal herniotomy had an inhalational
      induction with sevoflurane and were randomly allocated to sevoflurane (group S)
      or desflurane (group D) for maintenance. All infants received i.v. atracurium 0.5
      mg kg(-1), rectal acetaminophen 20 mg kg(-1) and caudal bupivacaine 0.25% 1 ml
      kg(-1). Infants were monitored for apnoeas (using nasal thermistry and
      impedance), haemoglobin oxygen desaturations and bradycardias for 12 h before and
      after operation with an Alice 4 polysomnograph. Emergence timings were recorded.
      RESULTS: There was no difference between pre- and postoperative incidence of
      apnoeas in either group, and no group difference between desflurane and
      sevoflurane in terms of pre- and postoperative ventilatory events or in the
      number of apnoeas in the postoperative period (nine patients in group D and five
      patients in group S had apnoeas). Median times to first movement, tracheal
      extubation, eye opening and first cry were all faster with group D (group D: 3.0,
      10.0, 9.0 and 11.0 min and group S: 7.0, 15.1, 13.5 and 16.1 min, respectively).
      No infant had problems with airway irritation on emergence and no infant required
      airway intervention for apnoea. CONCLUSIONS: Infants wake faster from general
      anaesthesia when maintained with desflurane as compared with sevoflurane, but no
      difference in postoperative respiratory events was demonstrated between the
      groups.

PMID- 16648153
TI  - The significance of premature luteinization in an oocyte-donation programme.
AB  - BACKGROUND: Several evidences indicate that premature luteinization (PL) may
      affect IVF outcome. The primary end-point of the present study was to verify the
      effect of PL on the pregnancy rate (PR) of our oocyte-donation programme.
      METHODS: PL was defined as serum progesterone > or = 1.2 ng/ml on the day of HCG.
      We analysed retrospectively 240 oocyte-donation cycles in which 120 women donated
      twice, with PL in the first donation cycle and no PL in the following one, acting
      as its own control. Recipients (n = 240) were divided in two groups according to
      the presence of PL (n = 120) or not (n = 120). Both groups were compared
      regarding donor cycle parameters and recipient cycle outcome. RESULTS: There was
      no difference in PR between the groups (55.7 versus 54.4%, respectively). The
      number of total oocytes (18.2 +/- 0.6 versus 20.8 +/- 0.6; P = 0.003) and the
      number of mature oocytes retrieved (16.9 +/- 0.6 versus 19.4 +/- 0.6; P = 0.005)
      were different among donors with progesterone < 1.2 ng/ml and PL, respectively.
      There were no differences between the oocyte recipients in fertilization,
      cleavage, embryo division on day 3, blastocyst development or fragmentation
      rates. The number of embryos transferred, number of embryos cryopreserved, and
      implantation and miscarriage rates were similar between the groups. CONCLUSION:
      PL does not appear to have a negative impact on ongoing PR in our oocyte-donation
      programme.

PMID- 16648154
TI  - Quantitative measurement and visual assessment of ileal Crohn's disease activity
      by computed tomography enterography: correlation with endoscopic severity and C
      reactive protein.
AB  - BACKGROUND: Few studies have correlated computed tomography (CT) enterography
      findings with endoscopic severity and C reactive protein (CRP) concentrations.
      AIM: To examine whether small bowel inflammation at CT enterography correlates
      with endoscopic severity and CRP in patients with Crohn's disease (CD). METHODS:
      CT enterography datasets from 143 CD patients undergoing ileoscopy were examined
      for three different CT parameters: CT bowel enhancement, as defined by the ratio
      of terminal ileal versus control ileal loop attenuation; vascular enlargement of
      the vasa recta ("the comb sign"); and mesenteric fat density. Correlations
      between CT scan parameters, endoscopy, and histology severity scores, and CRP
      were assessed using Spearman's rank correlation and logistic regression. RESULTS:
      Endoscopic score was significantly correlated with CT bowel enhancement, comb
      sign, and fat density (Spearman correlation coefficients 0.33-0.39; p<0.001).
      Correlations with histological inflammation were strongest for bowel enhancement
      (r = 0.34-0.38; p<0.001). CRP was elevated in patients with increased fat density
      versus those with increased bowel enhancement only (median 0.96 v 0.23, p =
      0.002). CRP did not differ significantly between patients without evidence of
      active Crohn's and those with bowel enhancement and endoscopic inflammation not
      involving the perienteric tissues by CT (median 0.24 v 0.36; p = 0.38).
      CONCLUSION: Quantitative measures of bowel enhancement at CT enterography
      correlate with endoscopic and histological severity. CRP correlates with
      radiological findings of perienteric inflammation (increased fat density), but
      not of inflammation limited to the small bowel wall, underscoring the potential
      role of perienteric inflammation in CRP response in CD.

PMID- 16648155
TI  - Gut-associated bacterial microbiota in paediatric patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Clinical and experimental observations in animal models indicate that
      intestinal commensal bacteria are involved in the initiation and amplification of
      inflammatory bowel disease (IBD). No paediatric reports are available on
      intestinal endogenous microflora in IBD. AIMS: To investigate and characterise
      the predominant composition of the mucosa-associated intestinal microflora in
      colonoscopic biopsy specimens of paediatric patients with newly diagnosed IBD.
      METHODS: Mucosa-associated bacteria were quantified and isolated from biopsy
      specimens of the ileum, caecum and rectum obtained at colonoscopy in 12 patients
      with Crohn's disease, 7 with ulcerative colitis, 6 with indeterminate colitis, 10
      with lymphonodular hyperplasia of the distal ileum and in 7 controls. Isolation
      and characterisation were carried out by conventional culture techniques for
      aerobic and facultative-anaerobic microorganisms, and molecular analysis (16S
      rRNA-based amplification and real-time polymerase chain reaction assays) for the
      detection of anaerobic bacterial groups or species. RESULTS: A higher number of
      mucosa-associated aerobic and facultative-anaerobic bacteria were found in biopsy
      specimens of children with IBD than in controls. An overall decrease in some
      bacterial species or groups belonging to the normal anaerobic intestinal flora
      was suggested by molecular approaches; in particular, occurrence of Bacteroides
      vulgatus was low in Crohn's disease, ulcerative colitis and indeterminate colitis
      specimens. CONCLUSION: This is the first paediatric report investigating the
      intestinal mucosa-associated microflora in patients of the IBD spectrum. These
      results, although limited by the sample size, allow a better understanding of
      changes in mucosa-associated bacterial flora in these patients, showing either a
      predominance of some potentially harmful bacterial groups or a decrease in
      beneficial bacterial species. These data underline the central role of mucosa
      adherent bacteria in IBD.

PMID- 16648156
TI  - Evolution of the Isd11-IscS complex reveals a single alpha-proteobacterial
      endosymbiosis for all eukaryotes.
AB  - Giardia and Trichomonas are eukaryotes without standard mitochondria but contain
      mitochondrial-type alpha-proteobacterium-derived iron-sulfur cluster (ISC)
      assembly proteins, located to mitosomes in Giardia and hydrogenosomes in
      Trichomonas. Although these data suggest a single common endosymbiotic ancestry
      for mitochondria, mitosomes, and hydrogenosomes, separate origins are still being
      proposed. Here, we present a bioinformatic analysis of Isd11, a recently
      described essential component of the mitochondrial ISC assembly pathway. Isd11 is
      unique to eukaryotes but functions closely with the alpha-proteobacterium-derived
      cysteine desulfurase IscS. We demonstrate the presence of homologues of Isd11 in
      all 5 eukaryotic supergroups sampled, including hydrogenosomal and mitosomal
      lineages. The eukaryotic invention of Isd11 as a functional partner to IscS
      directly implies a single shared alpha-proteobacterial endosymbiotic ancestry for
      all eukaryotes. This pinpoints the alpha-proteobacterial endosymbiosis to before
      the last common ancestor of all eukaryotes without ambiguity.

PMID- 16648158
TI  - Single molecule mechanical probing of the SNARE protein interactions.
AB  - Exocytotic release of neurotransmitters is mediated by the ternary soluble N
      ethyl maleimide-sensitive fusion protein attachment protein receptors (SNAREs)
      complex, comprised of syntaxin (Sx), synaptosome-associated protein of 25 kDa
      (SNAP25), and synaptobrevin 2 (Sb2). Since exocytosis involves the nonequilibrium
      process of association and dissociation of bonds between molecules of the SNARE
      complex, dynamic measurements at the single molecule level are necessary for a
      detailed understanding of these interactions. To address this issue, we used the
      atomic force microscope in force spectroscopy mode to show from single molecule
      investigations of the SNARE complex, that Sx1A and Sb2 are zippered throughout
      their entire SNARE domains without the involvement of SNAP25. When SNAP25B is
      present in the complex, it creates a local interaction at the 0 (ionic) layer by
      cuffing Sx1A and Sb2. Force loading rate studies indicate that the ternary
      complex interaction is more stable than the Sx1A-Sb2 interaction.

PMID- 16648159
TI  - A fluctuation method to quantify in vivo fluorescence data.
AB  - Quantitative in vivo measurements are essential for developing a predictive
      understanding of cellular behavior. Here we present a technique that converts
      observed fluorescence intensities into numbers of molecules. By transiently
      expressing a fluorescently tagged protein and then following its dilution during
      growth and division, we observe asymmetric partitioning of fluorescence between
      daughter cells at each division. Such partition asymmetries are set by the actual
      numbers of proteins present, and thus provide a means to quantify fluorescence
      levels. We present a Bayesian algorithm that infers from such data both the
      fluorescence conversion factor and an estimate of the measurement error. Our
      algorithm works for arbitrarily sized data sets and handles consistently any
      missing measurements. We verify the algorithm with extensive simulation and
      demonstrate its application to experimental data from Escherichia coli. Our
      technique should provide a quantitative internal calibration to systems biology
      studies of both synthetic and endogenous cellular networks.

PMID- 16648160
TI  - Modeling Starburst cells' GABA(B) receptors and their putative role in motion
      sensitivity.
AB  - Neal and Cunningham (Neal, M. J., and J. R. Cunningham. 1995. J. Physiol.
      (Lond.). 482:363-372) showed that GABA(B) agonists and glycinergic antagonists
      enhance the light-evoked release of retinal acetylcholine. They proposed that
      glycinergic cells inhibit the cholinergic Starburst amacrine cells and are in
      turn inhibited by GABA through GABA(B) receptors. However, as recently shown,
      glycinergic cells do not appear to have GABA(B) receptors. In contrast, the
      Starburst amacrine cell has GABA(B) receptors in a subpopulation of its
      varicosities. We thus propose an alternate model in which GABA(B)-receptor
      activation reduces the release of ACh from some dendritic compartments onto a
      glycinergic cell, which then feeds back and inhibits the Starburst cell. In this
      model, the GABA necessary to make these receptors active comes from the Starburst
      cell itself, making them autoreceptors. Computer simulations of this model show
      that it accounts quantitatively for the Neal and Cunningham data. We also argue
      that GABA(B) receptors could work to increase the sensitivity to motion over
      other stimuli.

PMID- 16648161
TI  - Insight into the binding of antifreeze proteins to ice surfaces via 13C spin
      lattice relaxation solid-state NMR.
AB  - The primary sequences of type I antifreeze proteins (AFPs) are Ala rich and
      contain three 11-residue repeat units beginning with threonine residues. Their
      secondary structures consist of alpha-helices. Previous activity study of side
      chain mutated AFPs suggests that the ice-binding side of type I AFPs comprises
      the Thr side chains and the conserved i + 4 and i + 8 Ala residues, where i
      indicates the positions of the Thrs. To find structural evidence for the AFP's
      ice-binding side, a variable-temperature dependent (13)C spin lattice relaxation
      solid-state NMR experiment was carried out for two Ala side chain (13)C labeled
      HPLC6 isoforms of the type I AFPs each frozen in H(2)O and D(2)O, respectively.
      The first one was labeled on the equivalent 17th and 21st Ala side chains (i + 4,
      8), and the second one on the equivalent 8th, 19th, and 30th Ala side chains (i +
      6). The two kinds of labels are on the opposite sides of the alpha-helical AFP. A
      model of Ala methyl group rotation/three-site rotational jump combined with water
      molecular reorientation was tested to probe the interactions of the methyl groups
      with the proximate water molecules. Analysis of the T(1) data shows that there
      could be 10 water molecules closely capping an i + 4 or an i + 8 methyl group
      within the range of van der Waals interaction, whereas the surrounding water
      molecules to the i + 6 methyl groups could be looser. This study suggests that
      the side of the alpha-helical AFP comprising the i + 4 and i + 8 Ala methyl
      groups could interact with the ice surface in the ice/water interface.

PMID- 16648162
TI  - Testing simplified proteins models of the hPin1 WW domain.
AB  - The WW domain of the human Pin1 protein for its simple topology and large amount
      of experimental data is an ideal candidate to assess theoretical approaches to
      protein folding. The purpose of this work is to compare the reliability of the
      chemically based Sorenson/Head-Gordon (SHG) model and a standard native centric
      model in reproducing, through molecular dynamics simulations, some of the well
      known features of the folding transition of this small domain. Our results show
      that the Go model correctly reproduces the cooperative, two-state, folding
      mechanism of the WW-domain, while the SHG model predicts a transition occurring
      in two stages: a collapse, followed by a structural rearrangement. The lack of a
      cooperative folding in the SHG simulations appears to be related to the nonfunnel
      shape of the energy landscape featuring a partitioning of the native valley in
      subbasins corresponding to different chain chiralities. However, the SHG approach
      remains more reliable in estimating the phi-values with respect to Go-like
      description. This may suggest that the WW-domain folding process is stirred by
      energetic and topological factors as well, and it highlights the better
      suitability of chemically based models in simulating mutations.

PMID- 16648163
TI  - Influence of thermally driven surface undulations on tethers formed from bilayer
      membranes.
AB  - Tether formation is a powerful method to study the mechanical properties of soft
      lipid bilayer membranes. The force required to maintain a tether at a given
      length depends upon both membrane elastic properties and tension. In this report,
      we develop a theoretical analysis that considers the contribution of thermally
      driven surface undulations and the corresponding entropically driven tensions on
      the conformation of tethers formed from unaspirated lipid vesicles. In this
      model, thermal undulations of the vesicle surface provide the excess area
      required for tether formation. Energy minimization demonstrates the dependence of
      equilibrium tether conformation on membrane tension and provides an analytical
      relationship between tether force and radius. If the contributions of nonlocal
      bending are not considered, an analytical relationship between tether force and
      length can also be obtained. The predictions of the model are compared to
      recently reported experimental data, and a value for the initial vesicle tension
      is obtained. Since most analyses of tether formation from cells and unaspirated
      vesicles neglect the contributions of nonlocal bending, the appropriateness of
      this assumption is analyzed. The effect of surface microvesiculations on the
      tether force-length relation is also considered.

PMID- 16648164
TI  - The net orientation of nicotinic receptor transmembrane alpha-helices in the
      resting and desensitized states.
AB  - The net orientation of nicotinic acetylcholine receptor transmembrane alpha
      helices has been probed in both the activatable resting and nonactivatable
      desensitized states using linear dichroism Fourier-transform infrared
      spectroscopy. Infrared spectra recorded from reconstituted nicotinic
      acetylcholine receptor membranes after 72 h exposure to (2)H2O exhibit an intense
      amide I component band near 1655 cm(-1) that is due predominantly to hydrogen
      exchange-resistant transmembrane peptides in an alpha-helical conformation. The
      measured dichroism of this band is 2.37, suggesting a net tilt of the
      transmembrane alpha-helices of roughly 40 degrees from the bilayer normal,
      although this value overestimates the tilt angle because the measured dichroism
      at 1655 cm(-1) also reflects the dichroism of overlapping amide I component
      bands. Significantly, no change in the net orientation of the transmembrane alpha
      helices is observed upon agonist binding. In fact, the main changes in structure
      and orientation detected upon desensitization involve highly solvent accessible
      regions of the polypeptide backbone. Our data are consistent with a capping of
      the ligand binding site by the solvent accessible C-loop with little change in
      the structure of the transmembrane domain in the desensitized state. Changes in
      structure at the interface between the ligand-binding and transmembrane domains
      may uncouple binding from gating.

PMID- 16648165
TI  - Interlaced optical force-fluorescence measurements for single molecule
      biophysics.
AB  - Combining optical tweezers with single molecule fluorescence offers a powerful
      technique to study the biophysical properties of single proteins and molecules.
      However, such integration into a combined, coincident arrangement has been
      severely limited by the dramatic reduction in fluorescence longevity of common
      dyes under simultaneous exposure to trapping and fluorescence excitation beams.
      We present a novel approach to overcome this problem by alternately modulating
      the optical trap and excitation beams to prevent simultaneous exposure of the
      fluorescent dye. We demonstrate the dramatic reduction of trap-induced
      photobleaching effects on the common single molecule fluorescence dye Cy3, which
      is highly susceptible to this destructive pathway. The extension in
      characteristic fluorophore longevity, a 20-fold improvement when compared to
      simultaneous exposure to both beams, prolongs the fluorescence emission to
      several tens of seconds in a combined, coincident arrangement. Furthermore, we
      show that this scheme, interlaced optical force-fluorescence, does not compromise
      the trap stiffness or single molecule fluorescence sensitivity at sufficiently
      high modulation frequencies. Such improvement permits the simultaneous
      measurement of the mechanical state of a system with optical tweezers and the
      localization of molecular changes with single molecule fluorescence, as
      demonstrated by mechanically unzipping a 15-basepair DNA segment labeled with
      Cy3.

PMID- 16648166
TI  - On the accuracy of homology modeling and sequence alignment methods applied to
      membrane proteins.
AB  - In this study, we investigate the extent to which techniques for homology
      modeling that were developed for water-soluble proteins are appropriate for
      membrane proteins as well. To this end we present an assessment of current
      strategies for homology modeling of membrane proteins and introduce a benchmark
      data set of homologous membrane protein structures, called HOMEP. First, we use
      HOMEP to reveal the relationship between sequence identity and structural
      similarity in membrane proteins. This analysis indicates that homology modeling
      is at least as applicable to membrane proteins as it is to water-soluble proteins
      and that acceptable models (with C alpha-RMSD values to the native of 2 A or less
      in the transmembrane regions) may be obtained for template sequence identities of
      30% or higher if an accurate alignment of the sequences is used. Second, we show
      that secondary-structure prediction algorithms that were developed for water
      soluble proteins perform approximately as well for membrane proteins. Third, we
      provide a comparison of a set of commonly used sequence alignment algorithms as
      applied to membrane proteins. We find that high-accuracy alignments of membrane
      protein sequences can be obtained using state-of-the-art profile-to-profile
      methods that were developed for water-soluble proteins. Improvements are observed
      when weights derived from the secondary structure of the query and the template
      are used in the scoring of the alignment, a result which relies on the accuracy
      of the secondary-structure prediction of the query sequence. The most accurate
      alignments were obtained using template profiles constructed with the aid of
      structural alignments. In contrast, a simple sequence-to-sequence alignment
      algorithm, using a membrane protein-specific substitution matrix, shows no
      improvement in alignment accuracy. We suggest that profile-to-profile alignment
      methods should be adopted to maximize the accuracy of homology models of membrane
      proteins.

PMID- 16648167
TI  - Membrane-bound basic peptides sequester multivalent (PIP2), but not monovalent
      (PS), acidic lipids.
AB  - Several biologically important peripheral (e.g., myristoylated alanine-rich C
      kinase substrate) and integral (e.g., the epidermal growth factor receptor)
      membrane proteins contain clusters of basic residues that interact with acidic
      lipids in the plasma membrane. Previous measurements demonstrate that the
      polyvalent acidic lipid phosphatidylinositol 4,5-bisphosphate is bound
      electrostatically (i.e., sequestered) by membrane-adsorbed basic peptides
      corresponding to these clusters. We report here three experimental observations
      that suggest monovalent acidic lipids are not sequestered by membrane-bound basic
      peptides. 1), Binding of basic peptides to vesicles does not decrease when the
      temperature is lowered below the fluid-to-gel phase transition. 2), The binding
      energy of Lys-13 to lipid vesicles increases linearly with the fraction of
      monovalent acidic lipids. 3), Binding of basic peptides to vesicles produces no
      self-quenching of fluorescent monovalent acidic lipids. One potential explanation
      for these results is that membrane-bound basic peptides diffuse too rapidly for
      the monovalent lipids to be sequestered. Indeed, our fluorescence correlation
      spectroscopy measurements show basic peptides bound to
      phosphatidylcholine/phosphatidylserine membranes have a diffusion coefficient
      approximately twofold higher than that of lipids, and those bound to
      phosphatidylcholine/phosphatidylinositol 4,5-bisphosphate membranes have a
      diffusion coefficient comparable to that of lipids.

PMID- 16648168
TI  - Flexibility in a drug transport accessory protein: molecular dynamics simulations
      of MexA.
AB  - Drug resistance in gram-negative bacteria may be conferred via efflux through a
      tripartite complex of an inner membrane pump, an outer membrane pore, and a
      periplasmic adaptor protein. These are AcrB, TolC, and AcrA, respectively, in
      Escherichia coli. In Pseudomonas aerugonisa, their homologs are MexB, OprM, and
      MexA. Defining the interdomain dynamics of the adaptor protein is essential to
      understanding the mechanism of complex formation. Extended (25 ns) molecular
      dynamics simulations of MexA have been performed to determine such interdomain
      dynamics. Analysis of conformational drift demonstrates substantial motions of
      the three domains of MexA relative to one another. Principal components analysis
      reveals a hinge-bending motion and rotation of the alpha-helical hairpin relative
      to the other domains to be the two dominant motions. These two motions provide an
      element of considerable flexibility which is likely to be exploited in the
      adaptor function of MexA.

PMID- 16648169
TI  - Akt versus p53 in a network of oncogenes and tumor suppressor genes regulating
      cell survival and death.
AB  - The tumor suppressor protein, p53, and the oncoprotein, Akt, are involved in a
      cross talk that could be at the core of a cell's control machinery for switching
      between survival and death. This cross talk is a combination of reciprocally
      antagonistic pathways emanating from p53 and Akt, and also involves another tumor
      suppressor gene, PTEN, and another oncogene, Mdm2; such a connected network of
      cancer-relevant genes must be significant and demands a critical study. The p53
      Akt network is shown in this report to possess the potential to exhibit
      bistability, a phenomenon in which two stable steady states of the system coexist
      for a fixed set of control parameter values. A hierarchy of qualitative networks
      and abstract kinetic models are analyzed and simulated on a computer to
      demonstrate the robustness of the bistable behavior, which, as argued in this
      study, is a likely candidate mechanism for a cellular survival-death switch. The
      analysis applies to cells that are neither p53-null nor Akt-null. The models
      presented here offer experimental predictions on the identity of control
      parameters of apoptotic thresholds and on network perturbations (including DNA
      damage and Akt inhibition) that are sufficient to generate switching between pro
      survival and pro-death cellular states.

PMID- 16648170
TI  - Ground and excited states of retinal schiff base chromophores by
      multiconfigurational perturbation theory.
AB  - We have studied the wavelength dependence of retinal Schiff base absorbencies on
      the protonation state of the chromophore at the multiconfigurational level of
      theory using second order perturbation theory (CASPT2) within an atomic natural
      orbital basis set on MP2 optimized geometries. Quantitative agreement between
      calculated and experimental absorption maxima was obtained for protonated and
      deprotonated Schiff bases of all-trans- and 11-cis-retinal and intermediate
      states covering a wavelength range from 610 to 353 nm. These data will be useful
      as reference points for the calibration of more approximate schemes.

PMID- 16648171
TI  - Determining the ratio of the Gaussian curvature and bending elastic moduli of
      phospholipids from Q(II) phase unit cell dimensions.
AB  - A method is presented for measuring M, the ratio of the Gaussian (saddle splay)
      elastic modulus to the bending elastic modulus of a lipid monolayer. The ratio M
      is determined from measurements of the equilibrium bicontinuous inverted cubic
      (Q(II)) phase unit cell size in excess water as a function of temperature. The
      analysis includes the effect of a curvature elastic term that is second-order in
      the Gaussian curvature, K. Preliminary results using data on DOPE-Me validate the
      method. The fitted value of M is within 8% of the value estimated in an earlier
      treatment. The method can be used to measure changes in M due to addition of
      exogenous lipids and peptides to a host lipid system. The Gaussian elastic
      modulus has a substantial effect on the stability of fusion intermediates
      (stalks, hemifusion diaphragms, and fusion pores). Studying the effects of
      peptides and different lipids on M via this method may yield insights into how
      fusion protein moieties stabilize intermediates in membrane fusion in vivo. The
      contribution of the K2 curvature elastic term to the free energy of Q(II) phase
      and fusion pores explains some features of fusion pore stability and dynamics,
      and some peculiar observations concerning the mechanism of L(alpha)/Q(II) phase
      transitions.

PMID- 16648172
TI  - Ion-mediated nucleic acid helix-helix interactions.
AB  - Salt ions are essential for the folding of nucleic acids. We use the tightly
      bound ion (TBI) model, which can account for the correlations and fluctuations
      for the ions bound to the nucleic acids, to investigate the electrostatic free
      energy landscape for two parallel nucleic acid helices in the solution of added
      salt. The theory is based on realistic atomic structures of the helices. In
      monovalent salt, the helices are predicted to repel each other. For divalent
      salt, while the mean-field Poisson-Boltzmann theory predicts only the repulsion,
      the TBI theory predicts an effective attraction between the helices. The helices
      are predicted to be stabilized at an interhelix distance approximately 26-36 A,
      and the strength of the attractive force can reach -0.37 k(B)T/bp for helix
      length in the range of 9-12 bp. Both the stable helix-helix distance and the
      strength of the attraction are strongly dependent on the salt concentration and
      ion size. With the increase of the salt concentration, the helix-helix attraction
      becomes stronger and the most stable helix-helix separation distance becomes
      smaller. For divalent ions, at very high ion concentration, further addition of
      ions leads to the weakening of the attraction. Smaller ion size causes stronger
      helix-helix attraction and stabilizes the helices at a shorter distance. In
      addition, the TBI model shows that a decrease in the solvent dielectric constant
      would enhance the ion-mediated attraction. The theoretical findings from the TBI
      theory agree with the experimental measurements on the osmotic pressure of DNA
      array as well as the results from the computer simulations.

PMID- 16648173
TI  - Tetramer formation kinetics in the signaling state of AppA monitored by time
      resolved diffusion.
AB  - The photoreaction kinetics of the BLUF domain of AppA(5-125) was studied by
      monitoring time-dependence of an apparent diffusion coefficient (D) using the
      pulsed laser-induced transient grating technique. It was found that D of the
      photoproduct is time-dependent. From the concentration dependence of the reaction
      rate, it was concluded that the BLUF domain of AppA forms a dimer upon the
      photoexcitation. Since AppA exists as a dimeric form in the ground state, this
      dimerization reaction indicates the tetramer formation in the signaling state.
      From the slope of the plot of observed rate constants (k(obs)) against the AppA
      concentration, the second order rate constant is determined to be approximately
      2.5 x 10(5) M(-1) s(-1), which is approximately 4 orders in magnitude lower than
      the diffusion controlled reaction. It indicates that a relative orientation of
      the protein molecules during the dimerization process causes additional
      constraints, which slow down the reaction rate.

PMID- 16648174
TI  - Modeling Hsp70-mediated protein folding.
AB  - The Hsp70 chaperone system is the major molecular chaperone system that assists
      protein-folding processes in all cells. To understand these processes, we
      analyzed the kinetic characteristics of the Escherichia coli homologs of this
      chaperone system during folding of a denatured protein using computer simulations
      and compared the results with in vitro refolding experiments. Rate constants used
      for the model were derived from recent literature or were determined and
      scrutinized for their applicability to the refolding reaction. Our simulation
      results are consistent with reported laboratory experiments, not only simulating
      the refolding reaction of wild-type proteins but also the behavior of mutant
      variants. Variation of kinetic parameters and concentrations of components of the
      Hsp70 system demonstrate the robustness of the chaperone system in assisting
      protein folding. Furthermore, the importance of the synergistic stimulation of
      the ATPase activity of Hsp70 is demonstrated. The limitations of our kinetic
      model indicate sore spots in our understanding of this chaperone system. Our
      model provides a platform for further research on chaperone action and the
      mechanism of chaperone-assisted refolding of denatured proteins.

PMID- 16648175
TI  - Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat
      heart.
AB  - AMP-activated protein kinase (AMPK) plays a key role in modulating cellular
      metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex
      of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple
      isoforms. Mutations in the cardiac gamma(2)-isoform have been associated with
      hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological
      regulation of AMPK complexes containing different subunit isoforms is not well
      defined and is important for an understanding of the function of this signaling
      pathway in the intact heart. We evaluated the kinase activity associated with
      heart AMPK complexes containing specific alpha- and gamma-subunit isoforms of
      AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion
      activated the immunoprecipitated alpha(1)-isoform (6-fold, P < 0.01) and alpha(2)
      isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham
      controls. The degree of alpha-subunit activation depended on the extent of
      ischemia and paralleled echocardiographic contractile dysfunction. The regulatory
      gamma(1)- and gamma(2)-isoforms were expressed in the heart. The gamma(1)- and
      gamma(2)-isoforms coimmunoprecipitated with alpha(1)- and alpha(2)-isoforms in
      proportion to alpha-subunit content. gamma(1)-Isoform immunocomplexes accounted
      for 70% of AMPK activity and AMPK phosphorylation (Thr(172)) in hearts. Ischemia
      similarly increased AMPK activity associated with the gamma(1)- and gamma(2)
      isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic alpha(1)-
      and alpha(2)-isoforms are activated by regional ischemia in vivo in the heart,
      irrespective of the regulatory gamma(1)- or gamma(2)-isoforms to which they are
      complexed. Despite the pathophysiological importance of gamma(2)-isoform
      mutations, gamma(1)-isoform complexes account for most of the AMPK activity in
      the ischemic heart.

PMID- 16648176
TI  - Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and
      after hyperbaric oxygen exposure.
AB  - Accumulating evidence suggests that hyperbaric oxygen (HBO) stimulates neuronal
      nitric oxide (NO) synthase (NOS) activity, but the influence on endothelial NOS
      (eNOS) activity and vascular NO bioavailability remains unclear. We used a
      bioassay employing rat aortic rings to evaluate vascular NO bioavailability. HBO
      exposure to 2.8 atm absolute (ATA) in vitro decreased ACh relaxation. This effect
      remained unchanged, despite treatment with SOD-polyethylene glycol and catalase
      polyethylene glycol, suggesting that the reduction in endothelium-derived NO
      bioavailability was independent of superoxide production. In vitro HBO induced
      contraction of resting aortic rings with and without endothelium, and these
      contractions were reduced by the NOS inhibitor N(omega)-nitro-l-arginine. In
      addition, in vitro HBO attenuated the vascular contraction produced by
      norepinephrine, and this effect was reversed by N(omega)-nitro-l-arginine, but
      not by endothelial denudation. These findings indicate stimulation of
      extraendothelial NO production during HBO exposure. A radiochemical assay was
      used to assess NOS activity in rat aortic endothelial cells. Catalytic activity
      of eNOS in cell homogenates was not decreased by HBO, and in vivo HBO exposure to
      2.8 ATA was without effect on eNOS activity and/or vascular NO bioavailability in
      vitro. We conclude that HBO reduces endothelium-derived NO bioavailability
      independent of superoxide production, and this effect seems to be unrelated to a
      decrease in eNOS catalytic activity. In addition, HBO increases the resting tone
      of rat aortic rings and attenuates the contractile response to norepinephrine by
      endothelium-independent mechanisms that involve extraendothelial NO production.

PMID- 16648177
TI  - Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent
      protein kinase II in rat cardiac myocytes.
AB  - In this work we have combined biochemical and electrophysiological approaches to
      explore the modulation of rat ventricular transient outward K(+) current (I(to))
      by calmodulin kinase II (CaMKII). Intracellular application of CaMKII inhibitors
      KN93, calmidazolium, and autocamtide-2-related inhibitory peptide II (ARIP-II)
      accelerated the inactivation of I(to), even at low [Ca(2+)]. In the same
      conditions, CaMKII coimmunoprecipitated with Kv4.3 channels, suggesting that
      phosphorylation of Kv4.3 channels modulate inactivation of I(to). Because
      channels underlying I(to) are heteromultimers of Kv4.2 and Kv4.3, we have
      explored the effect of CaMKII on human embryonic kidney (HEK) cells transfected
      with either of those Kvalpha-subunits. Whereas Kv4.3 inactivated faster upon
      inhibition of CaMKII, Kv4.2 inactivation was insensitive to CaMKII inhibitors.
      However, Kv4.2 inactivation became slower when high Ca(2+) was used in the
      pipette or when intracellular [Ca(2+)] ([Ca(2+)](i)) was transiently increased.
      This effect was inhibited by KN93, and Western blot analysis demonstrated Ca(2+)
      dependent phosphorylation of Kv4.2 channels. On the contrary, CaMKII
      coimmunoprecipitated with Kv4.3 channels without a previous Ca(2+) increase, and
      the association was inhibited by KN93. These results suggest that both channels
      underlying I(to) are substrates of CaMKII, although with different sensitivities;
      Kv4.2 remain unphosphorylated unless [Ca(2+)](i) increases, whereas Kv4.3 are
      phosphorylated at rest. In addition to the functional impact that phosphorylation
      of Kv4 channels could cause on the shape of action potential, association of
      CaMKII with Kv4.3 provides a new role of Kv4.3 subunits as molecular scaffolds
      for concentrating CaMKII in the membrane, allowing Ca(2+)-dependent modulation by
      this enzyme of the associated Kv4.2 channels.

PMID- 16648178
TI  - Enhanced calcium mobilization in rat ventricular myocytes during the onset of
      pressure overload-induced hypertrophy.
AB  - Early cardiovascular changes evoked by pressure overload (PO) may reveal adaptive
      strategies that allow immediate survival to the increased hemodynamic load. In
      this study, systolic and diastolic Ca(2+) cycling was analyzed in left
      ventricular rat myocytes before (day 2, PO-2d group) and after (day 7, PO-7d
      group) development of hypertrophy subsequent to aortic constriction, as well as
      in myocytes from time-matched sham-operated rats (sham group). Ca(2+) transient
      amplitude was significantly augmented in the PO-2d group. In the PO-7d group,
      intracellular Ca(2+) concentration ([Ca(2+)](i)) was reduced during diastole, and
      mechanical twitch relaxation (but not [Ca(2+)](i) decline) was slowed. In PO
      groups, fractional sarcoplasmic reticulum (SR) Ca(2+) release at a twitch, SR
      Ca(2+) content, SR Ca(2+) loss during diastole, and SR-dependent integrated
      Ca(2+) flux during twitch relaxation were significantly greater than in sham
      operated groups, whereas the relaxation-associated Ca(2+) flux carried by the
      Na(+)/Ca(2+) exchanger was not significantly changed. In the PO-7d group, mRNA
      levels of cardiac isoforms of SR Ca(2+)-ATPase (SERCA2a), phospholamban,
      calsequestrin, ryanodine receptor, and NCX were not significantly altered, but
      the SERCA2a-to-phospholamban ratio was increased 2.5-fold. Moreover, greater
      sensitivity to the inotropic effects of the beta-adrenoceptor agonist
      isoproterenol was observed in the PO-7d group. The results indicate enhanced
      Ca(2+) cycling between SR and cytosol early after PO imposition, even before
      hypertrophy development. Increase in SR Ca(2+) uptake may contribute to
      enhancement of excitation-contraction coupling (augmented SR Ca(2+) content and
      release) and protection against arrhythmogenesis due to buildup of [Ca(2+)](i)
      during diastole.

PMID- 16648179
TI  - T wave alternans in an in vitro canine tissue model of Brugada syndrome.
AB  - Macroscopic T wave alternans (TWA) associated with increased occurrence of
      ventricular arrhythmias has been reported in patients with Brugada syndrome.
      However, the mechanisms in this syndrome are still unclear. We evaluated the
      hypothesis that TWA in Brugada syndrome was caused by the dynamic instability and
      heterogeneity of action potentials (APs) in the right ventricle. Using an optical
      mapping system, we mapped APs on the epicardium or transmural surfaces of 28
      isolated and arterially perfused canine right ventricular preparations having
      drug-induced Brugada syndrome (in micromol/l: 2.5-15 pinacidil, 5.0 terfenadine,
      and 5.0-13 pilsicainide). Bradycardia at cycle length (CL) of 2,632 +/- 496 ms (n
      = 19) induced alternating deep and shallow T waves in the transmural
      electrocardiogram. Compared with the shallow T waves, deep T waves were
      associated with epicardial APs having longer durations and larger domes. Adjacent
      regions having APs with alternating domes, with constant domes, and without domes
      coexisted simultaneously in the epicardium and caused TWA. In contrast to the
      alternating epicardial APs, midmyocardial and endocardial APs did not change
      during TWA. Alternans could be terminated by rapid (CL: 529 +/- 168 ms, n = 7) or
      very slow (CL: 3,000 ms, n = 7) pacing. The heterogeneic APs during TWA augmented
      the dispersion of repolarization both within the epicardium and from the
      epicardium to the endocardium and caused phase 2 reentry. In this drug-induced
      model of Brugada syndrome, heterogeneic AP contours and dynamic alternans in the
      dome of right ventricular epicardial, but not midmyocardial or endocardial, APs
      caused TWA and heightened arrhythmogenicity in part by increasing the dispersion
      of repolarization.

PMID- 16648180
TI  - Preconditioning by 17beta-estradiol in isolated rat heart depends on PI3-K/PKB
      pathway, PKC, and ROS.
AB  - To study the cell signaling events leading to 17beta-estradiol (E(2))-induced
      acute cardioprotection, we subjected isolated rat hearts to three 5-min cycles of
      10 microM E(2) before 30 min of regional ischemia, followed by 2 h of
      reperfusion. Protection was judged by changes in infarct size in percentage of
      risk zone volume. To test the importance of phosphoinositide 3-kinase (PI3-K),
      protein kinase C (PKC), or reactive oxygen species (ROS) in E(2)-induced
      protection, we combined wortmannin (1 microM), chelerythrine (2 microM), and 2
      mercaptopropionylglycine (300 microM), respectively, with E(2) exposure. Changes
      in phosphorylation of protein kinase B (PKB) and selected PKC isoforms were
      tested by immunoblotting of total lysates and subcellular fractions, along with
      assessment of PKC translocation from soluble to membrane fraction of heart tissue
      homogenates. Intracellular ROS levels induced by E(2) preconditioning were
      investigated. E(2) preconditioning led to significant reduction in infarct size
      from 31.8 +/- 5.3 to 20.2 +/- 2.6% in male hearts and from 42.7 +/- 4.7 to 17.1
      +/- 3.4% in female hearts (P < 0.05). Protection was abolished by wortmannin
      (30.0 +/- 3.2%), chelerythrine (45.1 +/- 4.4%), and 2-mercaptopropionylglycine
      (36.8 +/- 4.7%). E(2) preconditioning induced phosphorylation of PKB, PKCalpha,
      and PKCepsilon and membrane translocation of PKCepsilon and PKCdelta.
      Intracellular ROS levels were found elevated after transient treatment with
      hormone. Therefore, our data demonstrate the ability of E(2) to induce
      preconditioning-like cardioprotection via cell signaling events shared by classic
      ischemic preconditioning.

PMID- 16648181
TI  - Effects of adenosine on myocardial glucose and palmitate metabolism after
      transient ischemia: role of 5'-AMP-activated protein kinase.
AB  - Loss of cardioprotection by adenosine in hearts stressed by transient ischemia
      may be due to its effects on glucose metabolism. In the absence of transient
      ischemia, adenosine inhibits glycolysis, whereas it accelerates glycolysis after
      transient ischemia. Inasmuch as 5'-AMP-activated protein kinase (AMPK) is
      implicated as a regulator of glucose and fatty acid utilization, this study
      determined whether a differential alteration of AMPK activity contributes to
      acceleration of glycolysis by adenosine in hearts stressed by transient ischemia.
      Studies were performed in working rat hearts perfused aerobically under normal
      conditions or after transient ischemia (two 10-min periods of ischemia followed
      by 5 min of reperfusion). LV work was not affected by adenosine. AMPK
      phosphorylation was not affected by transient ischemia; however, phosphorylation
      and activity were increased nine- and threefold, respectively, by adenosine in
      stressed hearts. Phosphorylation of acetyl-CoA carboxylase and rates of palmitate
      oxidation were unaltered. Glycolysis and calculated proton production were
      increased 1.8- and 1.7-fold, respectively, in hearts with elevated AMPK activity.
      Elevated AMPK activity was associated with inhibition of glycogen synthesis and
      unchanged rates of glucose uptake and glycogenolysis. Phentolamine, an alpha
      adrenoceptor antagonist, which prevents adenosine-induced activation of
      glycolysis in stressed hearts, prevented AMPK phosphorylation. These data
      demonstrate that adenosine-induced activation of AMPK after transient ischemia is
      not sufficient to alter palmitate oxidation or glucose uptake. Rather, activation
      of AMPK alters partitioning of glucose away from glycogen synthesis; the increase
      in glycolysis may in part contribute to loss of adenosine-induced
      cardioprotection in hearts subjected to transient ischemia.

PMID- 16648182
TI  - Acute vascular responses to isometric handgrip exercise and effects of training
      in persons medicated for hypertension.
AB  - Previous work from our laboratory demonstrated that isometric handgrip (IHG)
      training improved local, endothelium-dependent vasodilation in medicated
      hypertensives [McGowan CL (PhD Thesis), 2006; McGowan et al. Physiologist 47:
      285, 2004]. We investigated whether changes in the capacity of smooth muscle to
      dilate (regardless of endothelial factors) influenced this training-induced
      change, and we examined the acute vascular responses to a single bout of IHG.
      Seventeen subjects performed four 2-min unilateral IHG contractions at 30% of
      maximal voluntary effort, three times a week for 8 wk. Pre- and posttraining,
      brachial artery flow-mediated dilation (FMD, an index of endothelium-dependent
      vasodilation) and nitroglycerin-mediated maximal vasodilation (an index of
      endothelium-independent vasodilation) were measured in the exercised arm by using
      ultrasound before and immediately after acute IHG exercise. IHG training resulted
      in improved resting brachial FMD (P < 0.01) and no change in nitroglycerin
      mediated maximal vasodilation. Pre- and posttraining, brachial artery FMD
      decreased following an acute bout of IHG exercise (normalized to peak shear rate,
      pre-, before IHG exercise: 0.01 +/- 0.002, after IHG exercise: 0.008 +/-
      0.002%/s(-1); post-, before IHG exercise: 0.020 +/- 0.003, after IHG exercise:
      0.010 +/- 0.003%/s(-1); P < 0.01). Posttraining, resting brachial artery FMD
      improved yet nitroglycerin-mediated maximal vasodilation was unchanged in persons
      medicated for hypertension. This suggests that the training-induced improvements
      in the resting brachial artery FMD were not due to underlying changes in the
      forearm vasculature. Acute IHG exercise attenuated brachial artery FMD, and
      although this impairment may be interpreted as hazardous to medicated
      hypertensives with already dysfunctional endothelium, the effects appear
      transient as repeated exposure to the IHG stimulus improved resting endothelium
      dependent vasodilation.

PMID- 16648183
TI  - Increased arterial load alters aortic structural and functional properties during
      embryogenesis.
AB  - As in the adult dorsal aorta, the embryonic dorsal aorta is an important
      determinant of cardiovascular function, and increased stiffness may have
      secondary effects on cardiac and microcirculatory development. We previously
      showed that acutely and chronically increased arterial load via vitelline artery
      ligation (VAL) increases systemic arterial stiffness. To test the hypothesis that
      local dorsal aortic stiffness also increases, we measured aortic pulse-wave
      velocity (PWV) and assessed the active and passive properties (stress and strain)
      of isolated aortic segments. PWV along the dorsal aorta increased acutely and
      chronically after VAL. Analysis of isolated aortic active properties suggests
      that load-exposed aortas experienced higher stress, but not strain, at similar
      intraluminal pressures. When smooth muscle tone was relaxed, strain decreased in
      VAL vessels, whereas stress became similar to control vessels.
      Immunohistochemical analysis revealed that although aortic smooth muscle alpha
      actin content was similar between groups, more cell layers expressed smooth
      muscle alpha-actin, and myocyte cell shape was markedly rounder in VAL embryos.
      Additionally, aortic and perivascular collagen type I and III content
      significantly increased in load-exposed VAL vessels. Increased production of
      these proteins is consistent with the observed increase in aortic PWV and
      decreased strain in VAL passive aortic segments. Thus the embryonic dorsal aorta
      is sensitive to increased arterial load and adapts by altering its material
      properties via changes in collagen content.

PMID- 16648184
TI  - Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic
      exposure in humans.
AB  - Systemic hemodynamics, including forearm blood flow and ventilatory parameters,
      were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic
      hypoxia. To evaluate the role of sympathetic nervous system activation in the
      changes, in 10 of these subjects, we measured muscle sympathetic nerve activity
      (MSNA) before and after exposure, and the remaining 11 subjects received intra
      arterial phentolamine infusion in the brachial artery to define vascular tone in
      the absence of sympathetically mediated vasoconstriction. Short-term ventilatory
      acclimatization occurred as evidenced by a decrease in resting Pco(2) (from 42 +/
      1.4 to 37 +/- 0.96 mmHg) and by an increase in the slope of the ventilatory
      response to acute hypoxia [from 0.7 +/- 0.1 to 1.2 +/- 0.2 l.min(-1).%Sp(O(2))
      (blood O(2) saturation from pulse oximetry)] after exposure. Subjects
      demonstrated a significant increase in resting heart rate (from 61 +/- 2 to 65 +/
      2 beats/min) and diastolic blood pressure (from 64.8 +/- 2.7 to 70.4 +/- 2.0
      mmHg). MSNA did not change significantly after exposure, although there was a
      trend toward a decrease in burst frequency (from 19.8 +/- 4.1 to 14.3 +/- 1.2
      bursts/min). Forearm vascular resistance showed a significant decrease after
      termination of exposure (from 37.7 +/- 3.6 to 27.6 +/- 2.7 mmHg.ml(-1).min.100 g
      tissue, P < 0.05). Initially, progressive isocapnic hypoxia elicited significant
      vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute
      challenge failed to change forearm vascular resistance. Local alpha-blockade with
      phentolamine restored the vasodilatory response to acute hypoxia in the
      postexposure setting.

PMID- 16648185
TI  - L-type calcium channel alpha-subunit and protein kinase inhibitors modulate Rem
      mediated regulation of current.
AB  - Cardiac voltage-gated L-type Ca channels (Ca(V)) are multiprotein complexes,
      including accessory subunits such as Ca(V)beta2 that increase current expression.
      Recently, members of the Rad and Gem/Kir-related family of small GTPases have
      been shown to decrease current, although the mechanism remains poorly defined. In
      this study, we evaluated the contribution of the L-type Ca channel alpha-subunit
      (Ca(V)1.2) to Ca(V)beta2-Rem inhibition of Ca channel current. Specifically, we
      addressed whether protein kinase A (PKA) modulation of the Ca channel modifies
      Ca(V)beta2-Rem inhibition of Ca channel current. We first tested the effect of
      Rem on Ca(V)1.2 in human embryonic kidney 293 (HEK-293) cells using the whole
      cell patch-clamp configuration. Rem coexpression with Ca(V)1.2 reduces Ba current
      expression under basal conditions, and Ca(V)beta2a coexpression enhances Rem
      block of Ca(V)1.2 current. Surprisingly, PKA inhibition by 133 nM H-89 or 50
      microM Rp-cAMP-S partially relieved the Rem-mediated inhibition of current
      activity both with and without Ca(V)beta2a. To test whether the H-89 action was a
      consequence of the phosphorylation status of Ca(V)1.2, we examined Rem regulation
      of the PKA-insensitive Ca(V)1.2 serine 1928 (S1928) to alanine mutation (Ca(V)1.2
      S1928A). Ca(V)1.2-S1928A current was not inhibited by Rem and when coexpression
      with Ca(V)beta2a was not completely blocked by Rem coexpression, suggesting that
      the phosphorylation of S1928 contributes to Rem-mediated Ca channel modulation.
      As a model for native Ca channel complexes, we tested the ability of Rem
      overexpression in HIT-T15 cells and embryonic ventricular myocytes to interfere
      with native current. We find that native current is also sensitive to Rem block
      and that H-89 pretreatment relieves the ability of Rem to regulate Ca current. We
      conclude that Rem is capable of regulating L-type current, that release of Rem
      block is modulated by cellular kinase pathways, and that the Ca(V)1.2 COOH
      terminus contributes to Rem-dependent channel inhibition.

PMID- 16648186
TI  - Cerebral autoregulation and CO2 responsiveness of the brain.

PMID- 16648187
TI  - Role of 12-lipoxygenase in volatile anesthetic-induced delayed preconditioning in
      mice.
AB  - Delayed cardiac protection mediated by 12-lipoxygenase (12-LO) expression and
      activity has been linked to opioid receptor stimulation. The role of 12-LO in
      volatile anesthetic-induced delayed cardiac protection has not been determined.
      We tested the hypothesis that expression and activity of 12-LO mediate delayed
      cardiac protection induced by isoflurane in the mouse heart in vivo. Mice were
      pretreated with 1.4% isoflurane for 30 min and allowed to recover for 1, 12, or
      24 h. Immunoblot analysis showed isoflurane significantly enhanced 12-LO protein
      expression at 12 and 24 h after isoflurane exposure, and this induction of 12-LO
      was confirmed by immunohistochemistry of whole heart sections at 24 h. The
      induced protein expression appeared to be localized to intercalated disc regions
      adjoining adjacent cardiac myocytes. Additionally, mice +/- isoflurane (24 h
      previously) were subjected to 30 min coronary artery occlusion followed by 2 h of
      reperfusion in the presence and absence of a 12-LO inhibitor. Isoflurane reduced
      infarct size (27.1 +/- 2.2% of the area at risk; n = 8) compared with the control
      group (44.6 +/- 3.6%, n = 8). Baicalein (3 mg/kg), a selective 12-LO inhibitor,
      blocked the delayed protective effects of isoflurane pretreatment on infarct size
      (40.6 +/- 3.6%, n = 8). These data suggest that 12-LO is an important mediator of
      isoflurane-induced delayed preconditioning.

PMID- 16648188
TI  - Relationship between muscle sympathetic nerve activity and systemic hemodynamics
      during nitric oxide synthase inhibition in humans.
AB  - Large interindividual differences exist in resting sympathetic nerve activity
      (SNA) among normotensive humans with similar arterial pressure (AP). We recently
      showed inverse relationships of resting SNA with cardiac output (CO) and vascular
      adrenergic responsiveness that appear to balance the influence of differences in
      SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)
      mediated vasodilation has a role in this balance by evaluating hemodynamic
      responses to systemic NO synthase (NOS) inhibition in individuals with low and
      high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography,
      CO via acetylene uptake and AP directly, at baseline and during increasing
      systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline
      MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA
      caused dose-dependent increases in AP and total peripheral resistance and reflex
      decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals
      with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in
      the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1
      mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP
      increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and
      smaller decreases in CO with L-NMMA, but changes in total peripheral resistance
      were not different between groups. We conclude that differences in CO among
      individuals with varying sympathetic traffic have important hemodynamic
      implications during disruption of NO-mediated vasodilation.

PMID- 16648189
TI  - Paradoxical coronary microcirculatory constriction during ischemia: a synergic
      function for nitric oxide and endothelin.
AB  - A paradoxical microcirculatory constriction has been observed in hearts of
      patients with ischemia, secondary to coronary stenosis. Here, using the isolated
      mouse heart (Langendorff), we examined the mechanism of this response, assuming
      involvement of nitric oxide (NO) and endothelin-1 (ET-1) systems. Perfusion
      pressure was maintained at 65 mmHg for 70 min (protocol 1), or it was reduced to
      30 mmHg over two intervals, between the 20- and 40-min marks (protocol 2) or from
      the 20-min mark onward (protocol 3). In protocol 1, coronary resistance (CR)
      remained steady in untreated heart, whereas it progressively increased during
      treatment with the NO synthesis inhibitor N(G)-nitro-l-arginine methyl ester (L
      NAME) (2.7-fold) or the ET(A) antagonist BQ-610 (2.8 fold). The ET(B) antagonist
      BQ-788 had instead no effect by itself but curtailed vasoconstriction to BQ-610.
      In protocol 2, hypotension raised CR by 2.2-fold. This response was blunted by
      reactive oxygen species (ROS) scavengers (mannitol and superoxide dismutase plus
      catalase) and was converted into vasodilation by l-NAME, BQ-610, or BQ-788.
      Restoration of normal pressure was followed by vasodilation and vasoconstriction,
      respectively, in untreated and treated preparations. In protocol 3, CR
      progressively increased with hypotension in the absence but not presence of L
      NAME or BQ-610. We conclude that the coronary vasculature is normally relaxed by
      two concerted processes, a direct action of NO and ET-1 curtailing an ET(B2)
      mediated tonic vasoconstriction through ET(A) activation. The negative feedback
      mechanism on ET(B2) subsides during hypotension, and the ensuing vasoconstriction
      is ascribed to ET-1 activating ET(A) and ET(B2) and reactive nitrogen oxide
      species originating from ROS-NO interaction.

PMID- 16648190
TI  - Biphasic changes in cardiac excitation-contraction coupling early in chronic
      alcohol exposure.
AB  - Although the negative inotropic effects of both acute and chronic ethanol (EtOH)
      exposure are well known, little is known concerning the acute-to-chronic
      transition of such effects. In this study, our objective was to address this
      question by detailing the effects that acute EtOH exposure induces on cellular
      excitation-contraction (EC) coupling and, subsequently, comparing whether and how
      such changes translate to the early chronic EtOH condition in a rat model known
      to develop alcohol-induced cardiomyopathy. Acute EtOH exposure, as formerly
      reported, indeed induced dose-dependent negative inotropic changes in cellular EC
      coupling, manifest as reductions in cell shortening, Ca2+ transient amplitude,
      Ca2+ decay rate, and sarcoplasmic reticulum Ca2+ content of isolated rat
      ventricular cardiac myocytes. Supplementary to this, we found Ca2+ spark
      character not to be significantly affected by acute EtOH exposure. In contrast,
      the results obtained from cardiac myocytes isolated from rats fed a diet
      containing approximately 9% (vol/vol) EtOH for 1 mo revealed changes in these
      parameters reflecting positive inotropy, whereas at 3 mo, these parameters again
      reflected negative inotropy similar but not identical to that induced by acute
      EtOH exposure. No significant changes were evident at either 1- or 3-mo chronic
      EtOH administration in echocardiographic parameters known to be perturbed in
      alcoholic cardiomyopathy (ACM), thus indicating that we were examining an
      asymptomatic stage in chronic EtOH administration consistent with an acute-to
      chronic transition phase. Continued study of such transition-phase events should
      provide important insight into which molecular-cellular components of EC coupling
      play pivotal roles in EtOH-induced disease processes, such as ACM.

PMID- 16648191
TI  - Cardioprotective role of endogenous hydrogen peroxide during ischemia-reperfusion
      injury in canine coronary microcirculation in vivo.
AB  - We have recently demonstrated that endogenous H2O2 plays an important role in
      coronary autoregulation in vivo. However, the role of H2O2 during coronary
      ischemia-reperfusion (I/R) injury remains to be examined. In this study, we
      examined whether endogenous H2O2 also plays a protective role in coronary I/R
      injury in dogs in vivo. Canine subepicardial small coronary arteries (>or=100
      microm) and arterioles (<100 microm) were continuously observed by an intravital
      microscope during coronary I/R (90/60 min) under cyclooxygenase blockade (n=50).
      Coronary vascular responses to endothelium-dependent vasodilators (ACh) were
      examined before and after I/R under the following seven conditions: control,
      nitric oxide (NO) synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA),
      catalase (a decomposer of H2O2), 8-sulfophenyltheophylline (8-SPT, an adenosine
      receptor blocker), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA, an inhibitor
      of large-conductance Ca2+-sensitive potassium channels), and L-NMMA+catalase+8
      SPT. Coronary I/R significantly impaired the coronary vasodilatation to ACh in
      both sized arteries (both P<0.01); L-NMMA reduced the small arterial
      vasodilatation (both P<0.01), whereas it increased (P<0.05) the ACh-induced
      coronary arteriolar vasodilatation associated with fluorescent H2O2 production
      after I/R. Catalase increased the small arterial vasodilatation (P<0.01)
      associated with fluorescent NO production and increased endothelial NOS
      expression, whereas it decreased the arteriolar response after I/R (P<0.01). L
      NMMA+catalase, L-NMMA+TEA, or L-NMMA+catalase+8-SPT further decreased the
      coronary vasodilatation in both sized arteries (both, P<0.01). L-NMMA+catalase, L
      NMMA+TEA, and L-NMMA+catalase+8-SPT significantly increased myocardial infarct
      area compared with the other four groups (control, L-NMMA, catalase, and 8-SPT;
      all, P<0.01). These results indicate that endogenous H2O2, in cooperation with
      NO, plays an important cardioprotective role in coronary I/R injury in vivo.

PMID- 16648192
TI  - MyD88 and NOS2 are essential for toll-like receptor 4-mediated survival effect in
      cardiomyocytes.
AB  - Innate immune system such as Toll-like receptor 4 (TLR4) represents the first
      line of defense against infection. In addition to its pivotal role in host
      immunity, recent studies have suggested that TLR4 may play a broader role in
      mediating tissue inflammation and cell survival in response to noninfectious
      injury. We and other investigators have reported that cardiac TLR4 signaling is
      dynamically modulated in ischemic myocardium and that activation of TLR4 confers
      a survival benefit in the heart and in isolated cardiomyocytes. However, the
      signaling pathways leading to these effects are not completely understood. Here,
      we investigate the role of MyD88, an adaptor protein of TLR4 signaling, and
      inducible nitric oxide synthase (NOS2) in mediating TLR4-induced cardiomyocyte
      survival in an in vitro model of apoptosis. Serum deprivation induced a
      significant increase in the number of apoptotic cardiomyocytes as demonstrated by
      transferase-mediated dUTP nick-end labeling (TUNEL) assay, nuclear morphology,
      DNA laddering, and DNA-histone ELISA. Lipopolysaccharide (LPS), a TLR4 agonist,
      activated TLR4 signaling and led to significant reduction in apoptotic
      cardiomyocytes and improved cellular function of surviving cardiomyocytes with
      enhanced Ca(2+) transients and cell shortening. We found that both TLR4 and MyD88
      are required for the LPS-induced beneficial effects as demonstrated by improved
      survival and function in wild-type but not in TLR4(-/-) or MyD88(-/-)
      cardiomyocytes. Moreover, genetic deletion or pharmacological inhibition of NOS2
      abolished survival and functional rescue of cardiomyocytes treated with LPS.
      Taken together, these data suggest that TLR4 protects cardiomyocytes from stress
      induced injury through MyD88- and NOS2-dependent mechanisms.

PMID- 16648193
TI  - Lack of activation of molecular forms of the BNP system in human grade 1
      hypertension and relationship to cardiac hypertrophy.
AB  - We evaluated relationships among two circulating molecular forms of brain
      natriuretic peptide (BNP32 and NT-proBNP), severity of hypertension (HTN), and
      cardiac hypertrophy in subjects with mild, moderate, and severe HTN. We
      prospectively studied 78 patients (43 males; mean age 51.4 +/- 11 yr) with
      essential HTN and 28 age- and sex-matched controls. BNP32 and NT-proBNP were
      measured by radioimmunoassay. In grade 1 HTN, BNP32 was not elevated and NT
      proBNP was reduced (P = 0.030) compared with controls. However, log-transformed
      values of BNP32 and NT-proBNP were both increased with severity of HTN from grade
      1 to 3 (P <0.0001 and P = 0.003, respectively). By multivariate analysis, log
      BNP32 was independently predicted by age (beta = 0.210, P = 0.026) and HTN grade
      (beta = 0.274, P = 0.004), whereas log NT-proBNP was independently predicted by
      sex (beta = 0.235, P = 0.012) and HTN grade (beta = 0.218, P = 0.0023). Two forms
      of BNP were measured in normal subjects and patients with essential HTN. In grade
      1 HTN, BNP32 was unchanged and NT-proBNP was significantly reduced compared with
      controls. As severity increased in humans with grade 1 to 3 HTN, both BNP32 and
      NT-proBNP levels were increased while not being affected by the presence of left
      ventricular hypertrophy. The lack of activation of BNP32 together with the
      reduction of NT-proBNP in grade 1 HTN may represent an impaired response of the
      BNP system in the early phase of HTN. The later activation of both forms of BNP
      may be a late compensatory effect, because it correlates with severity of HTN
      rather than cardiac hypertrophy/remodeling.

PMID- 16648194
TI  - Characterization of lymphangiogenesis in a model of adult skin regeneration.
AB  - To date, adult lymphangiogenesis is not well understood. In this study we
      describe the evolution of lymphatic capillaries in regenerating skin and
      correlate lymphatic migration and organization with the expression of matrix
      metalloproteinases (MMPs), immune cells, the growth factors VEGF-A and VEGF-C,
      and the heparan sulfate proteogylcan perlecan, a key component of basement
      membrane. We show that while lymphatic endothelial cells (LECs) migrate and
      organize unidirectionally, in the direction of interstitial fluid flow, they do
      not sprout into the region but rather migrate as single cells that later join
      together into vessels. Furthermore, in a modified "shunted flow" version of the
      model, infiltrated LECs fail to organize into functional vessels, indicating that
      interstitial fluid flow is necessary for lymphatic organization. Perlecan
      expression on new lymphatic vessels was only observed after vessel organization
      was complete and also appeared first in the distal region, consistent with the
      directionality of lymphatic migration and organization. VEGF-C expression peaked
      at the initiation of lymphangiogenesis but was reduced to lower levels throughout
      organization and maturation. In mice lacking MMP-9, lymphatics regenerated
      normally, suggesting that MMP-9 is not required for lymphangiogenesis, at least
      in mouse skin. This study thus characterizes the process of adult
      lymphangiogenesis and differentiates it from sprouting blood angiogenesis,
      verifies its dependence on interstitial fluid flow for vessel organization, and
      correlates its temporal evolution with those of relevant environmental factors.

PMID- 16648195
TI  - Continuous flow augments reactivity of rabbit carotid artery by reducing
      bioavailability of NO despite an increase in release of EDHF.
AB  - Experiments were designed to investigate the influence of steady flow and
      pressure on endothelial function in the rabbit carotid artery. Increases and
      decreases in isometric force were compared in static rings and perfused (5 or 50
      ml/min) segments of the same arteries in the presence and absence of endothelium.
      The alpha(1)-adrenoceptor agonist phenylephrine and the muscarinic agonist
      acetylcholine were applied as vasoconstrictor and vasodilator stimuli,
      respectively. Continuous flow (5 and 50 ml/min) reduced the cGMP content and
      shifted the concentration-response curve to phenylephrine to the left compared
      with nonperfused static rings. Removal of the endothelium abolished the
      differences in cGMP content and the sensitivity to phenylephrine between static
      rings and perfused segments. No difference in sensitivity to phenylephrine was
      observed in tissues treated with N(omega)-nitro-l-arginine methyl ester (l-NAME).
      Acetylcholine-evoked relaxations were increased in perfused segments. l-NAME
      nearly abolished the acetylcholine-evoked relaxation in static rings, whereas
      about one-half of the relaxation remained in segments exposed to flow. This
      remnant relaxation was blocked by inhibition of endothelial small- and
      intermediate-conductance calcium-activated potassium channels by apamin plus 1
      [(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34). These experiments
      demonstrate that continuous flow increases the constriction evoked by alpha(1)
      adrenergic activation in the rabbit carotid artery through a reduced influence of
      basally released endothelial NO and, furthermore, that luminal flow unmasks an
      ability of the endothelium to release a non-NO, noncyclooxygenase vasodilator,
      presumably endothelium-derived hyperpolarizing factor.

PMID- 16648197
TI  - Retributive reactions to suspected offenders: the importance of social
      categorizations and guilt probability.
AB  - In the current research, the author investigates the influence of social
      categorizations on retributive emotions (e.g., anger) and punishment intentions
      when people evaluate suspected offenders as independent observers. It is argued
      that information that guilt is certain or uncertain (i.e., guilt probability) has
      different consequences for retributive reactions to ingroup and outgroup
      suspects. In correspondence with predictions, results of four experiments showed
      that people reacted more negatively to ingroup than outgroup suspects when guilt
      was certain but that people reacted more negatively to outgroup than ingroup
      suspects when guilt was uncertain. It is concluded that guilt probability
      moderates the influence of social categorizations on people's retributive
      reactions to suspected offenders.

PMID- 16648196
TI  - Allogeneic haematopoietic stem cell transplantation for metastatic renal
      carcinoma in Europe.
AB  - BACKGROUND: An allogeneic antitumour effect has been reported for various
      cancers. We evaluated the experience of allogeneic haematopoietic stem cell
      transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21
      European centres. PATIENTS AND METHODS: Reduced intensity conditioning and
      peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched
      related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was
      cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor
      lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15
      (range 3-41) months. RESULTS: All but three patients engrafted. The cumulative
      incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic
      GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n =
      4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant,
      were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD
      II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR
      4.12, P < 0.001), DLI (HR 3.39, P < 0.001), <3 metastatic sites (HR 2.61, P =
      0.002) and a Karnofsky score >70 (HR 2.33, P = 0.03). Patients (n = 17) with
      chronic GVHD and given DLI had a 2-year survival of 70%. CONCLUSION: Patients
      with metastatic RCC, less than three metastatic locations and a Karnofsky score
      >70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD
      improved the patient survival.

PMID- 16648198
TI  - The future is now: prospective temporal self-appraisals among defensive
      pessimists and optimists.
AB  - Three studies found that prospective temporal self-appraisals can be part of
      defensive pessimists' strategy; they felt closer to equally distant negative than
      positive futures. In Study 1, defensive pessimists felt closer to future failures
      and reported more negative affect than those considering success. In Study 2,
      when manipulated negative futures were close, defensive pessimists felt bad and
      performed well; results suggested that viewing negative futures as close may be
      part of their natural strategy. Study 3 found that prospective self-appraisals
      influenced performances through felt preparation. Optimists did not use
      prospective self-appraisals (Study 1) and their performances were unaffected by
      manipulated temporal distance (Studies 2 and 3). Discussion centers on
      prospective self-appraisals and multiple strategies of defensive pessimists.

PMID- 16648199
TI  - Resistance can be good or bad: how theories of resistance and dissonance affect
      attitude certainty.
AB  - This research investigated how lay theories about resisting persuasion can affect
      attitude certainty. Specifically, people who believed that resistance was
      negative (i.e., implies close-mindedness) showed different levels of attitude
      certainty after resisting persuasive messages than people who believed resistance
      was positive (i.e., implies intelligence). When people held positive lay theories
      of resistance and overcame ostensibly strong arguments, they showed increased
      attitude certainty (compared to those who overcame ostensibly weak arguments).
      However, individuals who believed that resistance was negative did not show
      increases in attitude certainty when overcoming strong arguments. Experiment 2
      suggests that the effect of lay theories and perceived argument strength on
      attitude certainty was due to dissonance created by believing that resistance is
      undesirable but nonetheless resisting persuasion.

PMID- 16648200
TI  - Self-enhancement by social comparison: a prospective analysis.
AB  - A longitudinal investigation showed that self-enhancement by social comparison
      (assessing whether people perceive themselves more positively than they perceive
      others) was prospectively related to an increase in self-reported adjustment,
      controlling for the effects of narcissism. Better adjustment, including higher
      self-esteem, was not prospectively related to an increase in self-enhancement.
      The investigation also included a diary period, allowing the assessment of
      intrasubject covariation between daily reports of self-esteem and daily reports
      of perceived challenge and daily events (positive or negative). High (compared to
      low) self-enhancers were less likely to report lower self-esteem under higher
      challenge and less likely to report higher self-esteem under positive events.

PMID- 16648201
TI  - Defenders of a lost cause: terror management and violent resistance to the
      disengagement plan.
AB  - Two studies, conducted 3 months before the Israeli pullout from the Gaza Strip
      and the Northern West Bank, examined whether reminders of death would lead right
      wing Israelis to endorse violent resistance against the disengagement plan. More
      specifically, we hypothesized that this reaction would be particularly strong
      among participants high in denial--those who were unable to come to terms with
      the Israeli withdrawal. In Study 1 (N = 63), right-wing Israeli undergraduates
      were primed with death and asked to indicate whether they view violent resistance
      as legitimate and whether they would be willing to partake in such violence. In
      Study 2 (N = 42), Israeli settlers in the Gaza Strip completed a similar
      procedure as in Study 1. In both studies, primes of death led to greater support
      of violent resistance, but only among participants high in denial. The discussion
      examines the applicability of terror management theory to understanding real-life
      political crises.

PMID- 16648202
TI  - Sex differences in regret: all for love or some for lust?
AB  - Few sex differences in regret or counterfactual thinking are evident in past
      research. The authors discovered a sex difference in regret that is both domain
      specific (i.e., unique to romantic relationships) and interpretable within a
      convergence of theories of evolution and regulatory focus. Three studies showed
      that within romantic relationships, men emphasize regrets of inaction over action
      (which correspond to promotion vs. prevention goals, respectively), whereas women
      report regrets of inaction and action with equivalent frequency. Sex differences
      were not evident in other interpersonal regrets (friendship, parental, sibling
      interactions) and were not moderated by relationship status. Although the sex
      difference was evident in regrets centering on both sexual and nonsexual
      relationship aspects, it was substantially larger for sexual regrets. These
      findings underscore the utility of applying an evolutionary perspective to better
      understand goal-regulating, cognitive processes.

PMID- 16648203
TI  - Stereotypes focus defensive projection.
AB  - Defensive projection is the process of perceiving one's undesirable qualities in
      others. The present research shows how stereotypes guide and justify the
      projection of specific traits onto specific group members. In four studies, the
      authors demonstrated that people who experienced a threat to a specific dimension
      of their self-concept selectively activated this dimension in a stereotype and
      derogated stereotyped others on this dimension. They further showed that
      stereotyped individuals are more likely to serve as targets of projection than
      are nonstereotyped individuals. These results demonstrate the functional role of
      stereotypes in guiding and constraining motivated self-enhancement.

PMID- 16648204
TI  - The impact of self-construal on aesthetic preference for angular versus rounded
      shapes.
AB  - In this article, the authors examine the role of self-construal in aesthetic
      preference for angular versus rounded shapes. Previous research found an
      independent self-construal is associated with a confrontation approach to
      conflict resolution, whereas an interdependent self-construal is associated with
      compromise. Furthermore, the literature in empirical aesthetics suggests that
      angular shapes tend to generate confrontational associations, and rounded shapes
      tend to generate compromise associations. Accordingly, the authors propose
      individuals with independent self-construals should perceive angular shapes as
      more attractive, whereas individuals with interdependent self-construals should
      find rounded shapes more attractive. The authors argue this effect of self
      construal should be more pronounced when people expect that their shape
      preferences will be evaluated by others because culturally consistent responses
      will be more accessible in this situation. These hypotheses were largely
      confirmed in a field study that classified logos from a variety of countries and
      two experiments in which self-construal was experimentally primed.

PMID- 16648205
TI  - What the voice reveals: within- and between-category stereotyping on the basis of
      voice.
AB  - The authors report research that attempts to shift the traditional focus of
      visual cues to auditory cues as a basis for stereotyping. Moreover, their
      approach examines whether gender-signaling vocal cues lead not only to between
      category but also to within-category gender stereotyping. Study 1 showed that
      both men and women vary within category in how feminine their voices sound and
      that perceptions of vocal femininity are highly consensual. Furthermore, the
      measured acoustic characteristics that differed between gender were also related
      to perceptions of within-gender femininity. Subsequent studies demonstrated that
      variability in vocal femininity affects gender stereotyping when the targets are
      all of the same gender (Study 2) and when the targets are of different genders
      (Study 3). In the latter case, evidence of both category-based and feature-based
      stereotyping was found. Mediation analyses showed that the relationship between
      acoustics and stereotyping was in part due to femininity.

PMID- 16648206
TI  - Social networks and college drinking: probing processes of social influence and
      selection.
AB  - This study used a three-wave panel design (N = 119 complete cases for all waves)
      to test for social influence and selection in the relation of college students'
      heavy drinking and that of their social networks. Evidence emerged for both
      social influence and selection, leading the authors to probe more specialized
      issues related to each. Results regarding social influence revealed, further,
      that greater presence in the network of individuals that the focal respondent
      considered "drinking buddies" was predictive of one's own later drinking,
      controlling for potential confounds. Network demographic characteristics
      associated with a "risky" (i.e., heavy-drinking) network also were documented. An
      additional finding, important for selection, was that wave-to-wave change in
      average network drinking appeared to result primarily from network members with
      different drinking levels being added to and dropped from the network. Findings
      are discussed in the context of the recent renaissance in social-network
      research.

PMID- 16648207
TI  - The causes and consequences of an avoidance-focus for interracial interactions.
AB  - The current work examined the causes and consequences of non-Black people's
      desire to avoid interracial interactions (an avoidance-focus). Expecting to
      respond with racial bias in inter-racial interactions was argued to result in an
      avoidance-focus for such interactions, which was hypothesized to have negative
      implications for the quality of interracial interactions. Across three studies,
      feedback indicating that non-Black participants would respond with racial bias in
      interactions with Black people resulted in anxiety and the desire to avoid the
      interaction. In addition, when participants with an avoidance-focus interacted
      with a Black confederate (Study 2), they had shorter interactions that were rated
      as less pleasant by the confederate and participant as compared to those without
      an avoidance-focus. Avoidance-focused participants were less interested in future
      interactions and came across as more avoidant and biased to their partner than
      less avoidance-focused participants. The findings are discussed in terms of their
      implications for racial relations.

PMID- 16648208
TI  - Are the Peer Assessment Rating Index and the Index of Treatment Complexity,
      Outcome, and Need suitable measures for orthognathic outcomes?
AB  - The aim of this study was to determine which of two occlusal indices were the
      most appropriate for use in the assessment of orthognathic outcome. The indices
      used were the Peer Assessment Rating (PAR) Index and the Index of Treatment
      Complexity, Outcome, and Need (ICON). These indices were validated against the
      subjective assessments of treatment outcome and treatment improvement obtained
      from a panel of experienced orthodontic consultants. For the subjective
      assessment, intraexaminer agreement for ranking treatment outcome, from patient
      study models (30 models), was good. Interexaminer agreement for ranking treatment
      outcome, in the same way, was good or moderate. Intraexaminer agreement for
      ranking treatment improvement (30 start and finish pairs of models) was very good
      or good. Interexaminer agreement for ranking treatment improvement ranged from
      good to fair. All the patient study models were scored using PAR and ICON. The
      level of correlation between PAR and ICON scores of treatment outcome and the
      subjective ranking of treatment outcome was significant (P < 0.001). The level of
      correlation between PAR and ICON scores of treatment improvement and the
      subjective ranking of treatment improvement was also significant (P < 0.001). It
      is concluded that both PAR and ICON are suitable indices for assessing the
      clinical outcome of combined orthodontic treatment and orthognathic surgery.

PMID- 16648209
TI  - Changes in dentofacial morphology after adeno-/tonsillectomy in young children
      with obstructive sleep apnoea--a 5-year follow-up study.
AB  - The aim of this study was to compare a number of dentofacial variables and airway
      space in children suffering from obstructive sleep apnoea (OSA) syndrome with the
      corresponding variables in control children exhibiting a normal breathing
      pattern, to study the development of these variables prospectively over a 5-year
      period following treatment for OSA, and to compare the recorded changes with the
      corresponding changes occurring in the controls. The subjects were 17 children
      (10 boys and 7 girls, mean age 5.6 years) diagnosed with OSA syndrome. The
      treatment for the OSA was adeno-/tonsillectomy. The control group comprised 17
      age- and gender-matched children (mean age 5.8 years) without breathing problems.
      Lateral cephalograms were taken of the OSA children at baseline and then at 1, 3,
      and 5 years post-treatment. The control records comprised registrations at
      baseline and then after 1 and 5 years. In comparison with the controls, the OSA
      children exhibited a more posteriorly inclined mandible (P < 0.05), a more
      anteriorly inclined maxilla (P < 0.001), a greater lower anterior face height (P
      < 0.01), a shorter anterior cranial base (P < 0.01), retroclined upper and lower
      incisors (P < 0.05 and P < 0.01, respectively), reduced airway space (P < 0.05
      and P < 0.01), and a less pronounced nose (P < 0.05). At 5 years post-treatment,
      there were no statistically significant differences between the groups except for
      the lengths of the anterior cranial base and the nose which were still shorter (P
      < 0.05) in the patient group. OSA in young children has an unfavourable effect on
      the development of several dental and facial components. However, if OSA is
      diagnosed and treated at an early age, an almost complete normalization of
      dentofacial morphology may be achieved.

PMID- 16648210
TI  - Unilateral molar distalization with a modified slider.
AB  - Although there are numerous publications on bilateral non-compliance molar
      distalization appliances, there is limited information on problems such as
      asymmetrical unilateral Class II malocclusions. The aim of the present
      investigation was to examine the distalization of molars unilaterally in patients
      with a unilateral Class II molar relationship utilizing a Keles Slider, designed
      without a bite plane. Ten girls (mean age 13.94 +/- 2.13 years) and seven boys
      (mean age 13.12 +/- 1.51 years) comprised the study material. Following insertion
      of the appliance, the patients were seen monthly and the screw was reactivated
      every 2 months. After a super-Class I molar relationship was achieved, the
      appliance was removed and the molars were stabilized with a Nance appliance for 2
      months before the second-phase of orthodontic treatment. The Nance appliance was
      maintained in the palate until the end of canine distalization. Lateral
      cephalometric radiographs were obtained before and immediately after insertion of
      the molar distalizer. The results showed that the maxillary first molars were
      distalized bodily on average by 2.85 mm. The maxillary first premolars moved
      forward bodily 2 mm and were extruded 2.03 mm. In all, 1.32 mm of protrusion,
      1.12 mm of extrusion, and 1.79 degrees of proclination of the upper incisors were
      observed. The mandibular incisors and mandibular molars erupted 0.83 and 0.95 mm,
      respectively. The unilateral Keles Slider distalized molars successfully to a
      Class I molar relationship.

PMID- 16648211
TI  - Changes in the physical properties of human premolar cementum after application
      of 4 weeks of controlled orthodontic forces.
AB  - This study was performed to assess the relationship between the magnitude of
      orthodontic force and physical properties of individual human cementum, and to
      identify the sites that may be predisposed to root resorption. The findings may
      assist in relating physical properties of dental root cementum and its
      susceptibility to root resorption. Sixteen maxillary first premolar teeth were
      selected in eight orthodontic patients (three males and five females), mean age
      14.8 years (range 11.2-17.5 years), requiring first premolar extractions. In each
      patient, a light orthodontic force of 25 cN was applied buccally using a
      sectional archwire on the first premolar on one side, while a heavy force of 225
      cN was applied to the contralateral side. The teeth were extracted 4 weeks after
      initial force application. Hardness and elastic modulus were measured on the
      buccal and the lingual surfaces of the cementum at the cervical, middle, and
      apical third of the root. The results showed that the mean hardness and elastic
      modulus of cementum in the light force group were greater than in the heavy force
      group at all positions. There were highly significant differences in both
      hardness and elastic modulus between the heavy and light force groups (P < 0.01).
      The mean hardness and elastic modulus of cementum gradually decreased from the
      cervical to the apical regions for buccal as well as lingual surfaces in both
      groups. There was, however, an insignificant difference between hardness and
      elastic modulus on the buccal surface compared with the lingual surface (P <
      0.05). It was concluded that the hardness and elastic modulus of cementum were
      affected by the application of orthodontics forces.

PMID- 16648212
TI  - Estimating arch length discrepancy through Little's Irregularity Index for
      epidemiological use.
AB  - The objective of this study was to evaluate the diagnostic capability of Little's
      Irregularity Index (LII) in order to estimate the arch length discrepancy (ALD)
      in a dental arch. Dental casts with a full permanent dentition, excluding third
      molars, from 200 12- to-16-year-old schoolchildren from a representative high
      school located in Lima, Peru, were used. Incisal irregularity was measured using
      the LII, whereas ALD was calculated as the difference between available and
      required space in each dental arch anterior to the first permanent molars. The
      receiver-operator characteristic (ROC) curve was used to contrast the LII with
      three different dichotomized ALDs and locate optimized cut-off points.
      Correlation between ALD and LII was -0.68 (P < 0.001). According to ROC curves,
      LIIs of 2.45, 4.00, and 4.55 mm were the optimized cut-off points to estimate
      negative ALDs higher than 0, 3, and 6 mm, respectively. LII's highest diagnostic
      capability was found for estimating negative ALD greater than 3 mm with a
      sensibility of 0.78 and a specificity of 0.76. Based on the present findings, LII
      could potentially be used in epidemiological surveys as a valid and less time
      consuming measurement of crowding compared with ALD; however, further studies are
      needed to test the reliability of this approach in field settings.

PMID- 16648213
TI  - Foetal alcohol syndrome: a cephalometric analysis of patients and controls.
AB  - Foetal alcohol syndrome (FAS) consists of multi-system abnormalities and is
      caused by the excessive intake of alcohol during pregnancy. The teratogenic
      effect of alcohol on the human foetus has now been established beyond reasonable
      doubt and FAS is the most important human teratogenic condition known today. The
      purpose of this study was to analyse the craniofacial parameters of children with
      FAS and compare them with matched controls. Ninety children diagnosed with FAS
      (45 males, 45 females) and 90 controls were matched for age, gender, and social
      class. The mean age of the FAS children was 8.9 years with the controls slightly
      older at 9.1 years. This age difference was not significant (P = 0.34). A
      standard lateral cephalometric radiograph of each subject was taken. The
      radiographs were digitized for 20 linear and 17 angular measurements. These 37
      variables were formulated to assess the size, shape, and relative position of
      three craniofacial complexes: (1) the cranial base, (2) midface, and (3)
      mandible. In addition, nine variables were computed to compare the soft tissue
      profiles. The study showed that measurements related to face height and
      mandibular size appear to be the most important features when distinguishing FAS
      children. Overall, the FAS children in the present study presented with
      vertically and horizontally underdeveloped maxillae, together with features of
      long face syndrome with large gonial angles and a short ramus in relation to
      total face height. There was also a tendency for the development of an anterior
      open bite, which appears to be compensated for by an increase in the vertical
      dimension of the anterior alveolar process to bring the incisor teeth into
      occlusion. The latter adaptation occurred mainly in the mandible.

PMID- 16648214
TI  - Combined transcript and metabolite profiling of Arabidopsis leaves reveals
      fundamental effects of the thiol-disulfide status on plant metabolism.
AB  - In this study, we used gas chromatography-mass spectrometry analysis in
      combination with flux analysis and the Affymetrix ATH1 GeneChip to survey the
      metabolome and transcriptome of Arabidopsis (Arabidopsis thaliana) leaves in
      response to manipulation of the thiol-disulfide status. Feeding low
      concentrations of the sulfhydryl reagent dithiothreitol for 1 h at the end of the
      dark period led to posttranslational redox activation of ADP-glucose
      pyrophosphorylase and major alterations in leaf carbon partitioning, including an
      increased flux into major respiratory pathways, starch, cell wall, and amino acid
      synthesis, and a reduced flux to sucrose. This was accompanied by a decrease in
      the levels of hexose phosphates, while metabolites in the second half of the
      tricarboxylic acid cycle and various amino acids increased, indicating a
      stimulation of anaplerotic fluxes reliant on alpha-ketoglutarate. There was also
      an increase in shikimate as a precursor of secondary plant products and marked
      changes in the levels of the minor sugars involved in ascorbate synthesis and
      cell wall metabolism. Transcript profiling revealed a relatively small number of
      changes in the levels of transcripts coding for components of redox regulation,
      transport processes, and cell wall, protein, and amino acid metabolism, while
      there were no major alterations in transcript levels coding for enzymes involved
      in central metabolic pathways. These results provide a global picture of the
      effect of redox and reveal the utility of transcript and metabolite profiling as
      systemic strategies to uncover the occurrence of redox modulation in vivo.

PMID- 16648215
TI  - Gene expression programs during shoot, root, and callus development in
      Arabidopsis tissue culture.
AB  - Shoots can be regenerated from Arabidopsis (Arabidopsis thaliana) root explants
      in tissue culture through a two-step process requiring preincubation on an auxin
      rich callus induction medium. Regenerating tissues can be directed along
      different developmental pathways leading to the formation of shoots, new roots,
      or callus by transferring to the appropriate organ induction medium. Using gene
      profiling methods, we identified groups of genes that serve as molecular
      signatures of the different developmental processes, i.e. genes that were
      specifically up- or down-regulated on one developmental pathway, but not on
      others. One transcription factor gene that was up-regulated during early shoot
      development was RAP2.6L (At5g13330), a member of the ERF (ethylene response
      factor) subfamily B-4 of the ERF/APETALA2 transcription factor gene family.
      RAP2.6L functions in shoot regeneration because T-DNA knockdown mutations in the
      gene reduced the efficiency of shoot formation in tissue culture, but not normal
      embryo or seedling development. RAP2.6L promoter:beta-glucuronidase fusions
      demonstrated that the up-regulation of the gene during shoot regeneration was, at
      least in part, transcriptionally controlled. The promoter:beta-glucuronidase
      fusions also demonstrated that RAP2.6L expression was localized to the shoot and
      emerging leaves, but expression declined in the leaf lamina as leaves expanded. T
      DNA knockdown mutations in RAP2.6L reduced the expression of many genes that are
      normally up-regulated during shoot development including CUP-SHAPED COTYLEDON2
      that is involved in shoot meristem specification. Thus, RAP2.6L appears to be
      part of a network involved in regulating the expression of many other genes in
      shoot regeneration.

PMID- 16648216
TI  - Chlororespiratory reduction 6 is a novel factor required for accumulation of the
      chloroplast NAD(P)H dehydrogenase complex in Arabidopsis.
AB  - The chloroplast NAD(P)H dehydrogenase (NDH) complex is involved in photosystem I
      cyclic electron transport and chlororespiration in higher plants. An Arabidopsis
      (Arabidopsis thaliana) chlororespiratory reduction 6 (crr6) mutant lacking NDH
      activity was identified by means of chlorophyll fluorescence imaging.
      Accumulation of the NDH complex was impaired in crr6. Physiological
      characterization of photosynthetic electron transport indicated the specific
      defect of the NDH complex in crr6. In contrast to the CRR7 protein that was
      recently identified as a potential novel subunit of the NDH complex by means of
      the same screening, the CRR6 protein was stable under the crr2 mutant background
      in which the NDH complex does not accumulate. The CRR6 gene (At2g47910) encodes a
      novel protein without any known motif. Although CRR6 does not have any
      transmembrane domains, it is localized in the thylakoid membrane fraction of the
      chloroplast. CRR6 is conserved in phototrophs, including cyanobacteria, from
      which the chloroplast NDH complex has evolutionally originated, but not in
      Chlamydomonas reinhardtii, in which the NDH complex is absent. We believe that
      CRR6 is a novel specific factor for the assembly or stabilization of the NDH
      complex.

PMID- 16648217
TI  - High light response of the thylakoid proteome in arabidopsis wild type and the
      ascorbate-deficient mutant vtc2-2. A comparative proteomics study.
AB  - The thylakoid proteome of chloroplasts contains multiple proteins involved in
      antioxidative defense, protein folding, and repair. To understand this functional
      protein network, we analyzed the quantitative response of the thylakoid
      associated proteome of Arabidopsis (Arabidopsis thaliana) wild type and the
      ascorbate-deficient mutant vtc2-2 after transition to high light (HL; 1,000
      micromol photons m(-2) s(-1)). The soluble thylakoid proteomes of wild type and
      vtc2-2 were compared after 0, 1, 3, and 5 d of HL using two-dimensional gels with
      three independent experiments, followed by a multivariant statistical analysis
      and tandem mass spectrometry. After 5 d of HL, both wild-type and vtc2-2 plants
      accumulated anthocyanins, increased their total ascorbate content, and lost 10%
      of photosystem II efficiency, but showed no bleaching. Anthocyanin and total
      ascorbate concentrations in vtc2-2 were respectively 34% and 20% of wild type,
      potentially leading to enhanced oxidative stress in vtc2-2. Forty-five protein
      spots significantly changed as a consequence of genotype, light treatment, or
      both. Independent confirmation was obtained from western blots. The most
      significant response was the up-regulation of thylakoid YCF37 likely involved in
      photosystem I assembly, and specific fibrillins, a flavin reductase-like protein,
      and an aldolase, each located in thylakoid-associated plastoglobules. Fe
      superoxide dismutase was down-regulated in vtc2-2, while Cu,Zn-superoxide
      dismutase was up-regulated. vtc2-2 also showed a systematic up-regulation of a
      steroid dehydrogenase-like protein. A number of other stress-related proteins,
      several thylakoid proteases, and lumenal isomerases did not change, while PsbS
      increased in wild type upon light stress. These findings are discussed in terms
      of plastid metabolism and oxidative stress defense, and emphasize that
      understanding of the chloroplast stress-response network must include the
      enzymatic role of plastoglobules.

PMID- 16648218
TI  - Phosphorus deficiency decreases cell division and elongation in grass leaves.
AB  - Leaf growth in monocotyledons results from the flux of newly born cells out of
      the division zone and into the adjacent elongation-only zone, where cells reach
      their final length. We used a kinematic method to analyze the effect of
      phosphorus nutrition status on cell division and elongation parameters in the
      epidermis of Lolium perenne. Phosphorus deficiency reduced the leaf elongation
      rate by 39% due to decreases in the cell production rate (-19%) and final cell
      length (-20%). The former was solely due to a lower average cell division rate
      (0.028 versus 0.046 cell cell(-1) h(-1)) and, thus, a lengthened average cell
      cycle duration (25 versus 15 h). The number of division cycles of the initial
      cell progeny (five to six) and, as a result, the number of meristematic cells (32
      64) and division zone length were independent of phosphorus status. Accordingly,
      low-phosphorus cells maintained meristematic activity longer. Lack of effect of
      phosphorus deficiency on meristematic cell length implies that a lower division
      rate was matched to a lower elongation rate. Phosphorus deficiency did not affect
      the elongation-only zone length, thus leading to longer cell elongation duration
      (99 versus 75 h). However, the substantially reduced postmitotic average relative
      elongation rate (0.045 versus 0.064 mm mm(-1) h(-1)) resulted in shorter mature
      cells. In summary, phosphorus deficiency did not affect the general controls of
      cell morphogenesis, but, by slowing down the rates of cell division and
      expansion, it slowed down its pace.

PMID- 16648220
TI  - Polygalacturonase-inhibiting protein interacts with pectin through a binding site
      formed by four clustered residues of arginine and lysine.
AB  - Polygalacturonase-inhibiting protein (PGIP) is a cell wall protein that inhibits
      fungal polygalacturonases (PGs) and retards the invasion of plant tissues by
      phytopathogenic fungi. Here, we report the interaction of two PGIP isoforms from
      Phaseolus vulgaris (PvPGIP1 and PvPGIP2) with both polygalacturonic acid and cell
      wall fractions containing uronic acids. We identify in the three-dimensional
      structure of PvPGIP2 a motif of four clustered arginine and lysine residues
      (R183, R206, K230, and R252) responsible for this binding. The four residues were
      mutated and the protein variants were expressed in Pichia pastoris. The ability
      of both wild-type and mutated proteins to bind pectins was investigated by
      affinity chromatography. Single mutations impaired the binding and double
      mutations abolished the interaction, thus indicating that the four clustered
      residues form the pectin-binding site. Remarkably, the binding of PGIP to pectin
      is displaced in vitro by PGs, suggesting that PGIP interacts with pectin and PGs
      through overlapping although not identical regions. The specific interaction of
      PGIP with polygalacturonic acid may be strategic to protect pectins from the
      degrading activity of fungal PGs.

PMID- 16648219
TI  - Aging in legume symbiosis. A molecular view on nodule senescence in Medicago
      truncatula.
AB  - Rhizobia reside as symbiosomes in the infected cells of legume nodules to fix
      atmospheric nitrogen. The symbiotic relation is strictly controlled, lasts for
      some time, but eventually leads to nodule senescence. We present a comprehensive
      transcriptomics study to understand the onset of nodule senescence in the legume
      Medicago truncatula. Distinct developmental stages with characteristic gene
      expression were delineated during which the two symbiotic partners were degraded
      consecutively, marking the switch in nodule tissue status from carbon sink to
      general nutrient source. Cluster analysis discriminated an early expression group
      that harbored regulatory genes that might be primary tools to interfere with pod
      filling-related or stress-induced nodule senescence, ultimately causing prolonged
      nitrogen fixation. Interestingly, the transcriptomes of nodule and leaf
      senescence had a high degree of overlap, arguing for the recruitment of similar
      pathways.

PMID- 16648221
TI  - Lentinula edodes tlg1 encodes a thaumatin-like protein that is involved in
      lentinan degradation and fruiting body senescence.
AB  - Lentinan is an antitumor product that is purified from fresh Lentinula edodes
      fruiting bodies. It is a cell wall component, comprising beta-1,3-glucan with
      beta-1,6-linked branches, which becomes degraded during postharvest preservation
      as a result of increased glucanase activity. In this study, we used N-terminal
      amino acid sequence to isolate tlg1, a gene encoding a thaumatin-like (TL)
      protein in L. edodes. The cDNA clone was approximately 1.0 kb whereas the genomic
      sequence was 2.1 kb, and comparison of the two indicated that tlg1 contains 12
      introns. The tlg1 gene product (TLG1) was predicted to comprise 240 amino acids,
      with a molecular mass of 25 kD and isoelectric point value of 3.5. The putative
      amino acid sequence exhibits approximately 40% identity with plant TL proteins,
      and a fungal genome database search revealed that these TL proteins are conserved
      in many fungi including the basidiomycota and ascomycota. Transcription of tlg1
      was not detected in vegetative mycelium or young and fresh mushrooms. However,
      transcription increased following harvest. Western-blot analysis demonstrated a
      rise in TLG1 levels following harvest and spore diffusion. TLG1 expressed in
      Escherichia coli and Aspergillus oryzae exhibited beta-1,3-glucanase activity
      and, when purified from the L. edodes fruiting body, demonstrated lentinan
      degrading activity. Thus, we suggest that TLG1 is involved in lentinan and cell
      wall degradation during senescence following harvest and spore diffusion.

PMID- 16648222
TI  - Phosphorus and aluminum interactions in soybean in relation to aluminum
      tolerance. Exudation of specific organic acids from different regions of the
      intact root system.
AB  - Aluminum (Al) toxicity and phosphorus (P) deficiency often coexist in acid soils
      that severely limit crop growth and production, including soybean (Glycine max).
      Understanding the physiological mechanisms relating to plant Al and P
      interactions should help facilitate the development of more Al-tolerant and/or P
      efficient crops. In this study, both homogeneous and heterogeneous nutrient
      solution experiments were conducted to study the effects of Al and P interactions
      on soybean root growth and root organic acid exudation. In the homogenous
      solution experiments with a uniform Al and P distribution in the bulk solution, P
      addition significantly increased Al tolerance in four soybean genotypes differing
      in P efficiency. The two P-efficient genotypes appeared to be more Al tolerant
      than the two P-inefficient genotypes under these high-P conditions. Analysis of
      root exudates indicated Al toxicity induced citrate exudation, P deficiency
      triggered oxalate exudation, and malate release was induced by both treatments.
      To more closely mimic low-P acid soils where P deficiency and Al toxicity are
      often much greater in the lower soil horizons, a divided root chamber/nutrient
      solution approach was employed to impose elevated P conditions in the simulated
      upper soil horizon, and Al toxicity/P deficiency in the lower horizon. Under
      these conditions, we found that the two P-efficient genotypes were more Al
      tolerant during the early stages of the experiment than the P-inefficient lines.
      Although the same three organic acids were exuded by roots in the divided chamber
      experiments, their exudation patterns were different from those in the
      homogeneous solution system. The two P-efficient genotypes secreted more malate
      from the taproot tip, suggesting that improved P nutrition may enhance exudation
      of organic acids in the root regions dealing with the greatest Al toxicity, thus
      enhancing Al tolerance. These findings demonstrate that P efficiency may play a
      role in Al tolerance in soybean. Phosphorus-efficient genotypes may be able to
      enhance Al tolerance not only through direct Al-P interactions but also through
      indirect interactions associated with stimulated exudation of different Al
      chelating organic acids in specific roots and root regions.

PMID- 16648223
TI  - Science, ethics, and the psychosocial treatment of ADHD.

PMID- 16648224
TI  - Twin study on heritability of activity, attention, and impulsivity as assessed by
      objective measures.
AB  - OBJECTIVE: The purpose of this study was to assess heritability of activity,
      attention, and impulsivity by comparing young monozygotic (MZ) twins with
      dizygotic (DZ) twins using objective measures. METHOD: The OPTAx test is an
      infrared motion analysis to record the movement pattern during a continuous
      performance test. Seventeen MZ and 12 same sexed DZ twin pairs in the range of 6
      to 12 years were tested. The zygosity was determined by DNA-fingerprinting. The
      measures under investigation were activity (microevents and spatial scaling),
      impulsivity (errors of commission), and attention (accuracy and variability). For
      statistical analyses, the classical model of Falconer and the ACE and ADE genetic
      model for twin data were applied in order to estimate the proportion of the
      variance in activity, impulsivity and attention that is due to genetic effects.
      RESULTS: The respective coefficients of intraclass correlations in MZ twins
      ranged between .35 and .65 whereas for DZ twins the correlations were between .12
      and .88. The heritability estimates resulting from both models were about 30% for
      4 of the 5 measures, but none of these was significantly different from 0.
      CONCLUSION: We found no significant influence of genetic factors for activity,
      attention, and impulsivity. The authors conclude that further investigation of
      heritability of ADHD is necessary using larger sample sizes and objective
      measures.

PMID- 16648225
TI  - Methylphenidate improves aspects of executive function in African American
      children with ADHD.
AB  - OBJECTIVE: The undertreatment of ethnic minority children with ADHD prompted a
      study on the effects of methylphenidate (MPH) on the executive functions of
      African American children with ADHD. METHOD: Nineteen African American children
      with ADHD are tested on the Tower of Hanoi (TOH) and the Paired Associates
      Learning Task (PAL) in a double-blind crossover acute challenge of MPH and
      placebo. RESULTS: Under MPH, TOH rule breaks decrease, especially in the second
      testing session, and TOH planning time increases, particularly for incorrect
      solutions; PAL recall in the final learning trial improves with MPH. CONCLUSION:
      Similar to previous findings with predominantly majority samples of patients with
      ADHD, MPH enhances planning, precision, and persistence in African American
      children with ADHD.

PMID- 16648226
TI  - A comparison of preferred treatment outcomes between children with ADHD and their
      parents.
AB  - OBJECTIVE: The newest guidelines for the treatment of ADHD call for the formation
      of an individualized treatment plan based on collaboration. Because the process
      of collaboration requires the communication of desired outcomes, the authors'
      goal is to examine the preferred outcomes of treatment for ADHD for children and
      parents. METHOD: A preferred outcomes questionnaire is used to gather data. A
      listing of the outcomes in ranked order is generated for each group. Spearman's
      rho is used to generate comparative data. RESULTS: Our results indicate a
      significant correlation between the preferred outcomes of the children and the
      parents. There is one outlier regarding the use of medication. CONCLUSION: The
      existence of the single outlier concerning the use of medication may infer that
      an assessment of the child's feelings regarding a medication regimen is
      therapeutically indicated.

PMID- 16648227
TI  - Peer and parenting characteristics of boys and girls with subclinical attention
      problems.
AB  - OBJECTIVE: This study examines peer and parenting characteristics of 149 boys and
      girls with and without subclinical attention problems. METHOD: Multivariate
      analyses showed that children with attention problems had higher levels of
      negative peer nominations and conflict and betrayal in friendships, and their
      parents tended to use higher levels of negative parenting characteristics
      compared to comparison children. Children with subclinical attention problems
      also reported lower levels of positive friendship qualities, and their parents
      tended to use lower levels of positive parenting characteristics than comparison
      children. RESULTS: Beyond normative gender differences (e.g., girls reported
      higher rates of parental involvement than boys), no significant group by gender
      interactions were found. CONCLUSION: These findings suggest that both girls and
      boys who were identified using a subclinical cutoff for attention problems have
      more difficulties relative to comparison peers across social domains of
      functioning.

PMID- 16648228
TI  - Decision making in children with ADHD only, ADHD-anxious/depressed, and control
      children using a child version of the Iowa Gambling Task.
AB  - OBJECTIVE: The goal of this study is to investigate decision making in children
      with ADHD using a child version of the Iowa Gambling Task (IGT). The effect of
      internalizing symptoms is also of interest. METHOD: Twenty-one children with ADHD
      (high anxiety/depression and no anxiety/depression) are compared to an age- and
      sex-matched control group on the gambling task. Children in the ADHD-alone group
      demonstrate impaired performance on the IGT. In contrast, children in the control
      group and the ADHD-anxiety/depression group learn to choose more from the
      advantageous decks over time. RESULTS: These findings of impaired decision making
      in children with ADHD parallel findings of real-life decision-making problems in
      this population. CONCLUSION: Furthermore, the findings suggest that having a high
      number of internalizing symptoms leads to better performance for children with
      ADHD on this variant of the IGT.

PMID- 16648229
TI  - Biases in ratings of disruptive behavior in children: effects of sex and negative
      halos.
AB  - OBJECTIVE: Behavior disorders are more prevalent among boys than girls, but the
      etiology of this difference is unclear. Studies have not tested for sex bias in
      ratings as a contributing factor to the differential sex prevalence rates.
      However, there are several studies showing "negative halo effects" in ratings of
      boys (i.e., the presence of one type of behavior artificially inflating ratings
      of another behavior). These findings have only been extended to girls in one
      recent study. The current study is designed to test for sex difference in (a)
      ratings of boys and girls who exhibit the same degree of disruptive behavior and
      (b) negative halo effects. METHOD: Two hundred and thirty-nine college students
      participated. Sex differences in ratings are not found. Nonetheless,
      bidirectional negative halo effects are found for boys and girls (i.e., the
      presence of oppositionality artificially increased ratings of inattention and
      hyperactivity; the presence of inattention and hyperactivity artificially
      increased oppositionality).

PMID- 16648230
TI  - Retrospective reports of childhood trauma in adults with ADHD.
AB  - OBJECTIVE: Although studies have documented higher prevalence of abuse in
      children with ADHD, no studies have investigated childhood reports of abuse in
      individuals identified with ADHD in adulthood. METHOD: Forty ADHD women, 17 ADHD
      males, 17 female controls, and 40 male controls complete the Childhood Trauma
      Questionnaire and other measures of psychosocial functioning. RESULTS: Emotional
      abuse and neglect are more common among men and women with ADHD as compared to
      controls. Sexual abuse and physical neglect are more commonly reported by females
      with ADHD. Although childhood abuse is significantly correlated with depression
      and anxiety in adulthood, having ADHD is a better predictor of poorer
      psychosocial functioning in adulthood. CONCLUSION: Clinicians are alerted that
      patients with ADHD symptoms have a high probability of childhood abuse.

PMID- 16648231
TI  - ADHD characteristics in Canadian Aboriginal children.
AB  - OBJECTIVE: The authors examine how many Aboriginal children attending two
      reservation-based elementary schools in Northern Alberta, Canada, would
      demonstrate symptoms associated with ADHD using standardized parent and teacher
      questionnaires. METHOD: Seventy-five Aboriginal children in Grades 1 through 4
      are tested. Seventeen of the 75 (22.7%) Aboriginal children demonstrated a match
      on parent and teacher forms, with T-scores greater than 1.5 standard deviations
      from the mean on the Conners' ADHD Index, Diagnostic and Statistical Manual of
      Mental Disorders (4th ed.; DSM-IV) Hyperactive/Impulsive Index, DSM-IV
      Inattentive Index, and/or DSM-IV Total Combined T-score. RESULTS: The number of
      Aboriginal children found to have symptoms associated with ADHD is significantly
      higher than expected based on prevalence rates in the general population.
      CONCLUSION: These findings suggest either a high prevalence of ADHD in Aboriginal
      children or unique learning and behavioral patterns in Aboriginal children that
      may erroneously lead to a diagnosis of ADHD if screening questionnaires are used.

PMID- 16648232
TI  - Psychometric properties of the Chinese version of the Conners' Parent and Teacher
      Rating Scales-Revised: Short Form.
AB  - OBJECTIVE: This article examines the psychometric properties of the Chinese
      version of the Conners' Parent and Teacher Rating Scales-Revised: Short Forms
      (CPRS-R:S-C and CTRS-R:S-C) in a representative sample of 2,584 first to ninth
      graders in Taipei and 479 clinical participants (274 with ADHD). METHOD: The
      instruments include the CPRS-R:S-C, CTRS-R:S-C, and the Chinese version of the
      Swanson, Kotkin, Atkins, M-Flynn, and Pelham Scale. RESULTS: Results show
      satisfactory factor structure, test-retest reliability, internal consistency, and
      convergent validity for all the subscales of the CTRS-R:S-C and CPRS-R:S-C. They
      clearly distinguish clinical participants with ADHD from those without.
      CONCLUSION: Our findings suggest that the CPRS-R:S-C and CTRS-R:S-C are reliable
      and valid instruments for measuring inattention and hyperactivity in both
      clinical and community settings in the Chinese population in Taipei.

PMID- 16648236
TI  - Neurotrophin effects on intracellular Ca2+ and force in airway smooth muscle.
AB  - Neurotrophins [e.g., brain-derived neurotrophic factor (BDNF), neurotrophin 4
      (NT4)], known to affect neuronal structure and function, are expressed in
      nonneuronal tissues including the airway. However, their function is unclear. We
      examined the effect of acute vs. prolonged neurotrophin exposure on regulation of
      airway smooth muscle (ASM) intracellular Ca(2+) concentration ([Ca(2+)](i)):
      sarcoplasmic reticulum (SR) Ca(2+) release and Ca(2+) influx (specifically store
      operated Ca(2+) entry, SOCE). Human ASM cells were incubated for 30 min in medium
      (control) or 1 or 10 nM BDNF, NT3, or NT4 (acute exposure) or overnight in 1 nM
      BDNF, NT3, or NT4 (prolonged exposure) and imaged after loading with the Ca(2+)
      indicator fura-2 AM. [Ca(2+)](i) responses to ACh, histamine, bradykinin, and
      caffeine and SOCE following SR Ca(2+) depletion were compared across cell groups.
      Force measurements were performed in human bronchial strips exposed to
      neurotrophins. Basal [Ca(2+)](i), peak responses to all agonists, SOCE, and force
      responses to ACh and histamine were all significantly enhanced by both acute and
      prolonged BDNF exposure (smaller effect of NT4) but decreased by NT3. Inhibition
      of the BDNF/NT4 receptor trkB by K252a prevented enhancement of [Ca(2+)](i)
      responses. ASM cells showed positive immunostaining for BDNF, NT3, NT4, trkB, and
      trkC (NT3 receptor). These novel data demonstrate that neurotrophins influence
      ASM [Ca(2+)](i) and force regulation and suggest a potential role for
      neurotrophins in airway diseases.

PMID- 16648237
TI  - Hepcidin expression and iron transport in alveolar macrophages.
AB  - Alveolar macrophages express many proteins important in iron homeostasis,
      including the iron importer divalent metal transport 1 (DMT1) and the iron
      exporter ferroportin 1 (FPN1) that likely participate in lung defense. We found
      the iron regulatory hormone hepcidin (HAMP) is also produced by alveolar
      macrophages. In mouse alveolar macrophages, HAMP mRNA was detected at a low level
      when not stimulated but at a high level when exposed to lipopolysaccharide (LPS).
      LPS also affected the mRNA levels of the iron transporters, with DMT1 being
      upregulated and FPN1 downregulated. However, iron had no effect on HAMP
      expression but was able to upregulate both DMT1 and FPN1 in alveolar macrophages.
      IL-1 and IL-6, which are important in HAMP augmentation in hepatocytes, also did
      not affect HAMP expression in alveolar macrophages. In fact, the LPS-induced
      alterations in the expression of HAMP as well as DMT1 and FPN1 were preserved in
      the alveolar macrophages isolated from IL-1 receptor or IL-6-deficient mice. When
      alveolar macrophages were loaded with transferrin-bound (55)Fe, the subsequent
      release of (55)Fe was inhibited significantly by LPS. In addition, treatment of
      these cells with either LPS or HAMP caused the diminishment of the surface FPN1.
      These findings are consistent with the current model that HAMP production leads
      to a decreased iron efflux. Our studies suggest that iron mobilization by
      alveolar macrophages can be affected by iron and LPS via several pathways,
      including HAMP-mediated degradation of FPN1, and that these cells may use unique
      regulatory mechanisms to cope with iron imbalance in the lung.

PMID- 16648238
TI  - TGF-beta1 in SP-A preparations influence immune suppressive properties of SP-A on
      human CD4+ T lymphocytes.
AB  - Surfactant protein A (SP-A) and transforming growth factor-beta1 (TGF-beta1) have
      been shown to modulate the functions of different immune cells and specifically
      to inhibit T lymphocyte proliferation. The aim of the present study was to
      elucidate whether the Smad signaling pathway, which is activated by TGF-beta1,
      also plays a role in SP-A-mediated inhibition of CD4+ T lymphocyte activation.
      Recombinant human SP-A1 expressed in Chinese hamster ovary cells [rSP-A1m
      (mammalian)], but not recombinant Baculovirus-derived rSP-A1hyp (hydroxyproline
      deficient), suppressed T lymphocyte proliferation and IL-2 mRNA expression. To
      test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was
      transfected in primary human CD4+ T lymphocytes. Only rSP-A1m, but not rSP-A1hyp,
      induced Smad-specific reporter genes, Smad2 phosphorylation, and Smad7 mRNA
      expression. The effect of rSP-A1m was mediated through the TGF-betaRII and could
      be antagonized by anti-TGF-beta1 neutralizing antibodies and sTGF-betaRII.
      Western blot and ELISA analysis revealed that rSP-A1m, but not rSP-A1hyp,
      contained TGF-beta1. TGF-beta1 was responsible for the differences in inhibition
      of CD4+ T lymphocyte proliferation and activation of the Smad signaling pathway
      between rSP-A1m and rSP-A1hyp. After acidification, native SP-A, obtained from
      patients with alveolar proteinosis, also induced Smad signaling in human CD4+ T
      lymphocytes leading to an increased inhibition of T lymphocyte proliferation,
      thus indicating the presence of inactive, latent TGF-beta1 in native SP-A
      samples. Association between SP-A and latent TGF-beta1 provides a possible novel
      mechanism to regulate TGF-beta1-mediated inflammation and fibrosis reactions in
      the lung but also leads to possible misinterpretation of immune-modulator
      functions of SP-A. Monitoring of SP-A preparations for possible TGF-beta1 is
      essential.

PMID- 16648239
TI  - A novel bronchial ring bioassay for the evaluation of small airway smooth muscle
      function in mice.
AB  - Advances in our understanding of murine airway physiology have been hindered by
      the lack of suitable, ex vivo, small airway bioassay systems. In this study, we
      introduce a novel small murine airway bioassay system that permits the
      physiological and pharmacological study of intrapulmonary bronchial smooth muscle
      via a bronchial ring (BR) preparation utilizing BR segments as small as 200
      microm in diameter. Using this ex vivo BR bioassay, we characterized small airway
      smooth muscle contraction and relaxation in the presence and absence of bronchial
      epithelium. In control BRs, the application of mechanical stretch is followed by
      spontaneous bronchial smooth muscle relaxation. BRs pretreated with methacholine
      (MCh) partially attenuate this stretch-induced relaxation by as much as 42%
      compared with control. MCh elicited a dose-dependent bronchial constriction with
      a maximal tension (E(max)) of 8.7 +/- 0.2 mN at an EC(50) of 0.33 +/- 0.02
      microM. In the presence of nifedipine, ryanodine, 2-aminoethoxydiphenyl borate,
      and SKF-96365, E(max) to MCh was significantly reduced. In epithelium-denuded
      BRs, MCh-induced contraction was significantly enhanced to 11.4 +/- 1.0 mN with
      an EC(50) of 0.16 +/- 0.04 microM (P < 0.01). Substance P relaxed MCh
      precontracted BR by 62.1%; however, this bronchial relaxation effect was
      completely lost in epithelium-denuded BRs. Papaverine virtually abolished MCh
      induced constriction in both epithelium-intact and epithelium-denuded bronchial
      smooth muscle. In conclusion, this study introduces a novel murine small airway
      BR bioassay that allows for the physiological study of smooth muscle airway
      contractile responses that may aid in our understanding of the pathophysiology of
      asthma.

PMID- 16648240
TI  - Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury.
AB  - Substantial progress has been made in understanding the contribution of
      alterations in coagulation and fibrinolysis to the pathogenesis of acute lung
      injury (ALI). Findings from mouse, rat, baboon, and human studies indicate that
      alterations in coagulation and fibrinolysis may be of major pathogenetic
      importance in ALI and other inflammatory conditions in the lung including
      pneumonia, sepsis, and ventilator-induced lung injury. Therapies targeted at both
      activation of coagulation through the extrinsic coagulation cascade and
      modulation of coagulation through the protein C system have the potential to
      favorably impact clinical ALI/acute respiratory distress syndrome.

PMID- 16648241
TI  - Cell signaling underlying the pathophysiology of pneumonia.
AB  - The symposium addressed the burgeoning interest in fundamental mechanisms
      underlying the onset of pneumonia. Bacteria exploit the lung's innate immune
      mechanism, resulting in pathophysiological cell signaling. As a consequence
      inflammation develops, leading to pneumonia. New mechanisms have been identified
      by which bacteria or bacterial products in the airway induce cross-compartmental
      signaling that leads to inflammatory consequences. The speakers addressed
      activation of the transcription factor, NF-kappaB occurring as a consequence of
      bacterial interactions with specific receptors, such as the Toll-like receptors
      and the TNF receptor 1 (Prince), or as a consequence of cytokine induction
      (Mizgerd). Also considered were mechanisms of bacterial virulence in the clinical
      setting (Wiener-Kronish) and the role of alveolar-capillary signaling mechanisms
      in the initiation of lung inflammation.

PMID- 16648242
TI  - Cyclic exposure to ozone alters distal airway development in infant rhesus
      monkeys.
AB  - Inner city children exposed to high levels of ozone suffer from an increased
      prevalence of respiratory diseases. Lung development in children is a long-term
      process, and there is a significant period of time during development when
      children growing up in urban areas are exposed to oxidant air pollution. This
      study was designed to test whether repeating cycles of injury and repair caused
      by episodes of ozone exposure lead to chronic airway disease and decreased lung
      function by altering normal lung maturation. We evaluated postnatal lung
      morphogenesis and function of infant monkeys after 5 mo of episodic exposure of
      0.5 parts per million ozone beginning at 1 mo of age. Nonhuman primates were
      chosen because their airway structure and postnatal lung development is similar
      to those of humans. Airway morphology and structure were evaluated at the end of
      the 5-mo exposure period. Compared with control infants, ozone-exposed animals
      had four fewer nonalveolarized airway generations, hyperplastic bronchiolar
      epithelium, and altered smooth muscle bundle orientation in terminal and
      respiratory bronchioles. These results suggest that episodic exposure to
      environmental ozone compromises postnatal morphogenesis of tracheobronchial
      airways.

PMID- 16648243
TI  - Increased bleomycin-induced lung injury in mice deficient in the transcription
      factor T-bet.
AB  - The reasons for variable sensitivity among and within species to lung injury and
      fibrosis caused by bleomycin (BLM) are unknown. Because T helper (Th) 1 and 2
      (Th1 and Th2) polarization of CD4+ T lymphocytes is one of the factors that
      affects the BLM response, we hypothesized that preventing expression of the Th1
      transcription factor T-bet would render BLM-resistant BALB/c mice sensitive to
      BLM. Wild-type and T-bet-deficient (T-bet-/-) BALB/c mice were treated with BLM
      or saline solution intratracheally. After BLM treatment, collagen content in the
      lung increased twofold by day 14 in lungs from T-bet-/- mice but was unaffected
      in lungs from wild-type BALB/c mice. These findings were confirmed by collagen
      staining of histopathological sections. BLM treatment significantly increased
      respiratory frequency and decreased tidal volume by day 14 in T-bet-/- mice but
      had no effect in wild-type mice. Lung fibrosis in BLM-treated T-bet-/- mice was
      associated with increased circulating levels of Th2 cytokines and increased
      expression of the profibrotic factor transforming growth factor-beta1. Depletion
      of CD4+, but not CD8+, T cells in T-bet-/- mice diminished BLM-induced lung
      fibrosis and the expression of transforming growth factor-beta1. These data
      suggest that the T-bet pathway in CD4+ T lymphocytes can confer resistance to BLM
      induced lung fibrosis in BALB/c mice.

PMID- 16648244
TI  - Occlusion of the coronary sinus: a complication of resynchronisation therapy for
      severe heart failure.
AB  - The finding of complete obstruction of the proximal coronary sinus after left
      ventricular (LV) lead extraction during LV lead replacement is uncommon. In our
      case, we used a large collateral branch of the middle cardiac vein as an
      alternative route to the postero-lateral region. We have termed this the
      'collateral approach'.

PMID- 16648245
TI  - Pacing site and bradycardia dependent retrograde conduction block over an
      atrioventricular accessory pathway.
AB  - Intermittent retrograde conduction over an accessory pathway (AP) is an uncommon
      phenomenon. We report a case of Wolff-Parkinson-White syndrome in which
      retrograde conduction of the bypass tract was present only during right
      ventricular (RV) outflow tract and left ventricular pacing or during RV inflow
      tract pacing with a fast pacing rate (pacing site and bradycardia dependent
      conduction block). The interaction between different branches/fibres of the
      bypass tract might explain the mechanism of this phenomenon. The AP was
      successfully ablated at the lateral aspect of mitral valve annulus. It is
      suggested that careful evaluation by decremental ventricular stimulation should
      be applied from multiple sites both during baseline study and after apparent AP
      ablation in order to detect such uncommon cases of intermittent conduction.

PMID- 16648246
TI  - Microfabricated bioprocessor for integrated nanoliter-scale Sanger DNA
      sequencing.
AB  - An efficient, nanoliter-scale microfabricated bioprocessor integrating all three
      Sanger sequencing steps, thermal cycling, sample purification, and capillary
      electrophoresis, has been developed and evaluated. Hybrid glass
      polydimethylsiloxane (PDMS) wafer-scale construction is used to combine 250-nl
      reactors, affinity-capture purification chambers, high-performance capillary
      electrophoresis channels, and pneumatic valves and pumps onto a single
      microfabricated device. Lab-on-a-chip-level integration enables complete Sanger
      sequencing from only 1 fmol of DNA template. Up to 556 continuous bases were
      sequenced with 99% accuracy, demonstrating read lengths required for de novo
      sequencing of human and other complex genomes. The performance of this
      miniaturized DNA sequencer provides a benchmark for predicting the ultimate cost
      and efficiency limits of Sanger sequencing.

PMID- 16648247
TI  - The circadian basis of winter depression.
AB  - The following test of the circadian phase-shift hypothesis for patients with
      winter depression (seasonal affective disorder, or SAD) uses low-dose melatonin
      administration in the morning or afternoon/evening to induce phase delays or
      phase advances, respectively, without causing sleepiness. Correlations between
      depression ratings and circadian phase revealed a therapeutic window for optimal
      alignment of circadian rhythms that also appears to be useful for phase-typing
      SAD patients for the purpose of administering treatment at the correct time.
      These analyses also provide estimates of the circadian component of SAD that may
      apply to the antidepressant mechanism of action of appropriately timed bright
      light exposure, the treatment of choice. SAD may be the first psychiatric
      disorder in which a physiological marker correlates with symptom severity before,
      and in the course of, treatment in the same patients. The findings support the
      phase-shift hypothesis for SAD, as well as suggest a way to assess the circadian
      component of other psychiatric, sleep, and chronobiologic disorders.

PMID- 16648248
TI  - An essential role for the DXPas34 tandem repeat and Tsix transcription in the
      counting process of X chromosome inactivation.
AB  - A counting process senses the X chromosome/autosome ratio and ensures that X
      chromosome inactivation (XCI) initiates in the early female (XX) embryo and in
      differentiating female ES cells but not in their male (XY) counterparts. Counting
      depends on the X inactivation center (Xic), which contains the Xist gene encoding
      a nuclear RNA, which coats the inactive X chromosome and induces gene silencing.
      A 37-kb sequence lying 3' to the Xist gene is known to prevent initiation of XCI
      in male differentiating ES cells. This region contains the major and minor
      promoters of the Tsix gene, which runs antisense to Xist, and the DXPas34 tandem
      repeat lying close to the Tsix major promoter. We have addressed the role of
      these elements in counting by using male ES cells. Targeted deletion of DXPas34
      impaired recruitment of RNA-polymerase II and TFIIB at the Tsix major promoter,
      resulting in low levels of Tsix expression in ES cells and moderate ectopic
      initiation of XCI upon differentiation. A deletion extending 3' to Xist and
      including the Tsix major promoter resulted in almost complete impairment of Tsix
      transcription and in efficient ectopic XCI upon differentiation of male ES cells.
      Internal deletions within the Tsix gene did not affect significantly the level of
      antisense transcription within Xist and had only minor effects upon
      differentiation. Our results identify a function for DXPas34 in murine XCI and
      demonstrate the critical role of Tsix transcription in preventing XCI in
      differentiating male ES cells and in normal functioning of the counting pathway.

PMID- 16648249
TI  - Subcellular localization and functions of the barley stem rust resistance
      receptor-like serine/threonine-specific protein kinase Rpg1.
AB  - The Rpg1 gene confers resistance to many pathotypes of the stem rust fungus
      Puccinia graminis f. sp. tritici and has protected barley from serious disease
      losses for over 60 years. Rpg1 encodes a constitutively expressed protein with
      two tandem kinase domains. Fractionation by differential centrifugation and
      aqueous two-phase separation of the microsome proteins located Rpg1 mainly in the
      cytosol but also in the plasma membrane and intracellular membranes. Recombinant
      Rpg1 autophosphorylates in vitro intramolecularly only serine and threonine amino
      acids with a preference for Mn(2+) cations and a K(m) of 0.15 and a V(max) of
      0.47 nmol.min(-1).mg(-1) protein. The inability of wild-type Rpg1 to
      transphosphorylate a recombinant Rpg1 inactivated by site-directed mutation
      confirmed that Rpg1 autophosphorylation proceeds exclusively via an
      intramolecular mechanism. Site-directed mutagenesis of the two adjacent lysine
      residues in the ATP anchor of the two-kinase domains established that the first
      of the two tandem kinase domains is nonfunctional and that lysine 461 of the
      second domain is the catalytically active residue. Transgenic barley, expressing
      Rpg1 mutated in either the kinase 1 or 2 domains, were fully susceptible to P.
      graminis f. sp. tritici revealing requirement of both kinase domains for
      resistance. In planta-expressed Rpg1 mutant protein confirmed that mutation in
      domain 2, but not 1, rendered the protein incapable of autophosphorylation.

PMID- 16648250
TI  - A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding,
      behavioral arousal, and blood pressure in mice.
AB  - Here, we report the isolation and characterization of an endogenous peptide
      ligand of GPR103 from rat brains. The purified peptide was found to be the 43
      residue RF-amide peptide QRFP. We also describe two mouse homologues of human
      GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human
      GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in
      transfected cells. Systematic in situ hybridization analysis in mouse brains
      showed that QRFP is expressed exclusively in the periventricular and lateral
      hypothalamus, whereas the two receptor mRNAs are distinctly localized in various
      brain areas without an overlap to each other. When administered centrally in
      mice, QRFP induced feeding behavior, accompanied by increased general locomotor
      activity and metabolic rate. QRFP-induced food intake was abolished by
      preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y
      receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting
      and in genetically obese ob/ob and db/db mice. Central QRFP administration also
      evoked highly sustained elevation of blood pressure and heart rate. Our findings
      suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and
      behavioral functions and implicate this neuropeptide system in metabolic
      syndrome.

PMID- 16648251
TI  - Voltage sensor conformations in the open and closed states in ROSETTA structural
      models of K(+) channels.
AB  - Voltage-gated ion channels control generation and propagation of action
      potentials in excitable cells. Significant progress has been made in
      understanding structure and function of the voltage-gated ion channels,
      highlighted by the high-resolution open-state structure of the voltage-gated
      potassium channel, K(v)1.2. However, because the structure of the closed state is
      unknown, the gating mechanism remains controversial. We adapted the rosetta
      membrane method to model the structures of the K(v)1.2 and KvAP channels using
      homology, de novo, and domain assembly methods and selected the most plausible
      models using a limited number of experimental constraints. Our model of K(v)1.2
      in the open state is very similar in overall topology to the x-ray structure of
      this channel. Modeling of KvAP in the open state suggests that orientation of the
      voltage-sensing domain relative to the pore-forming domain is considerably
      different from the orientation in the K(v)1.2 open state and that the magnitude
      of the vertical movement of S4 is significantly greater. Structural modeling of
      closed state of K(v)1.2 suggests gating movement that can be viewed as a sum of
      two previously suggested mechanisms: translation (2-4 A) plus rotation (
      approximately 180 degrees ) of the S4 segment as proposed in the original
      "sliding helix" or "helical screw" models coupled with a rolling motion of the S1
      S3 segments around S4, similar to recent "transporter" models of gating. We
      propose a unified mechanism of voltage-dependent gating for K(v)1.2 and KvAP in
      which this major conformational change moves the gating charge across the
      electric field in an analogous way for both channels.

PMID- 16648252
TI  - Phylogeny, evolution, and biogeography of Asiatic Salamanders (Hynobiidae).
AB  - We sequenced 15 complete mitochondrial genomes and performed comprehensive
      molecular phylogenetic analyses to study the origin and phylogeny of the
      Hynobiidae, an ancient lineage of living salamanders. Our phylogenetic analyses
      show that the Hynobiidae is a clade with well resolved relationships, and our
      results contrast with a morphology-based phylogenetic hypothesis. These
      salamanders have low vagility and are limited in their distribution primarily by
      deserts, mountains, and oceans. Our analysis suggests that the relationships
      among living hynobiids have been shaped primarily by geography. We show that four
      toed species assigned to Batrachuperus do not form a monophyletic group, and
      those that occur in Afghanistan and Iran are transferred to the resurrected
      Paradactylodon. Convergent morphological characters in different hynobiid
      lineages are likely produced by similar environmental selective pressures. Clock
      independent molecular dating suggests that hynobiids originated in the Middle
      Cretaceous [ approximately 110 million years ago (Mya)]. We propose an "out of
      North China" hypothesis for hynobiid origins and hypothesize an ancestral stream
      adapted form. Given the particular distributional patterns and our molecular
      dating estimates, we hypothesize that: (i) the interior desertification from
      Mongolia to Western Asia began approximately 50 Mya; (ii) the Tibetan plateau (at
      least on the eastern fringe) experienced rapid uplift approximately 40 Mya and
      reached an altitude of at least 2,500 m; and (iii) the Ailao-Red River shear zone
      underwent the most intense orogenic movement approximately 24 Mya.

PMID- 16648253
TI  - A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC.
AB  - G3139, an 18-mer phosphorothioate antisense oligonucleotide targeted to the
      initiation codon region of the Bcl-2 mRNA, can induce caspase-dependent apoptosis
      via the intrinsic mitochondrial pathway in 518A2 and other melanoma cells. G3139
      mediated apoptosis appears to be independent of its ability to down-regulate the
      expression of Bcl-2 protein, because the release of mitochondrial cytochrome c
      precedes in time the down-regulation of Bcl-2 protein expression. In this study,
      we demonstrate the ability of G3139 and other phosphorothioate oligonucleotides
      to bind directly to mitochondria isolated from 518A2 cells. Furthermore, we show
      that this interaction leads to the release of cytochrome c in the absence of a
      mitochondrial membrane permeability transition. Our data further demonstrate that
      there is an interaction between G3139 and VDAC, a protein that can facilitate the
      physiologic exchange of ATP and ADP across the outer mitochondrial membrane.
      Evidence from the electrophysiologic evaluation of VDAC channels reconstituted
      into phospholipid membranes demonstrates that G3139 is capable of producing
      greatly diminished channel conductance, indicating a closed state of the VDAC.
      This effect is oligomer length-dependent, and the ability of phosphorothioate
      homopolymers of thymidine of variable lengths to cause the release of cytochrome
      c from isolated mitochondria of 518A2 melanoma cells can be correlated with their
      ability to interact with VDAC. Because it has been suggested that the closure of
      VDAC leads to the opening of another outer mitochondrial membrane channel through
      which cytochrome c can transit, thus initiating apoptosis, it appears that VDAC
      may be an important pharmacologic target of G3139.

PMID- 16648254
TI  - Deficiency of the zinc finger protein ZPR1 causes neurodegeneration.
AB  - Mutations that cause reduced expression of the full-length Survival Motor Neurons
      (SMN) protein are a major cause of spinal muscular atrophy (SMA), a disease
      characterized by degeneration of the alpha-motor neurons in the anterior horn of
      the spinal cord. The severity of SMA may be influenced by the actions of modifier
      genes. One potential modifier gene is represented by ZPR1, which is down
      regulated in patients with SMA and encodes a zinc finger protein that interacts
      with complexes formed by SMN. To test the functional significance of ZPR1 gene
      down-regulation, we examined a mouse model with targeted ablation of the Zpr1
      gene. We report that ZPR1-deficient mice exhibit axonal pathology and
      neurodegeneration. These data identify ZPR1 deficiency as a contributing factor
      in neurodegenerative disorders.

PMID- 16648255
TI  - Diffusion of isolated DNA molecules: dependence on length and topology.
AB  - The conformation and dynamics of circular polymers is a subject of considerable
      theoretical and experimental interest. DNA is an important example because it
      occurs naturally in different topological states, including linear, relaxed
      circular, and supercoiled circular forms. A fundamental question is how the
      diffusion coefficients of isolated polymers scale with molecular length and how
      they vary for different topologies. Here, diffusion coefficients D for relaxed
      circular, supercoiled, and linear DNA molecules of length L ranging from
      approximately 6 to 290 kbp were measured by tracking the Brownian motion of
      single molecules. A topology-independent scaling law D approximately L(-nu) was
      observed with nu(L) = 0.571 +/- 0.014, nu(C) = 0.589 +/- 0.018, and nu(S) = 0.571
      +/- 0.057 for linear, relaxed circular, and supercoiled DNA, respectively, in
      good agreement with the scaling exponent of nu congruent with 0.588 predicted by
      renormalization group theory for polymers with significant excluded volume
      interactions. Our findings thus provide evidence in support of several theories
      that predict an effective diameter of DNA much greater than the Debye screening
      length. In addition, the measured ratio D(Circular)/D(Linear) = 1.32 +/- 0.014
      was closer to the value of 1.45 predicted by using renormalization group theory
      than the value of 1.18 predicted by classical Kirkwood hydrodynamic theory and
      agreed well with a value of 1.31 predicted when incorporating a recently proposed
      expression for the radius of gyration of circular polymers into the Zimm model.

PMID- 16648256
TI  - Bone-marrow-derived stem cells repair basement membrane collagen defects and
      reverse genetic kidney disease.
AB  - Type IV collagen is a predominant component of basement membranes, and glomeruli
      of a kidney filter approximately 70-90 liters of plasma every day through a
      specialized glomerular basement membrane (GBM). In Alport syndrome, a progressive
      disease primarily affecting kidneys, mutations in GBM-associated type IV collagen
      genes (COL4A3, COL4A4, or COL4A5) lead to basement membrane structural defects,
      proteinuria, renal failure, and an absence of all three GBM collagen triple
      helical chains because of obligatory posttranslational assembly requirements.
      Here, we demonstrate that transplantation of wild-type bone marrow (BM) into
      irradiated COL4A3(-/-) mice results in a possible recruitment of BM-derived
      progenitor cells as epithelial cells (podocytes) and mesangial cells within the
      damaged glomerulus, leading to a partial restoration of expression of the type IV
      collagen alpha3 chain with concomitant emergence of alpha4 and alpha5 chain
      expression, improved glomerular architecture associated with a significant
      reduction in proteinuria, and improvement in overall kidney histology compared
      with untreated COL4A3(-/-) mice or irradiated COL4A3(-/-) mice with BM from adult
      COL4A3(-/-) mice. The alpha3(IV) collagen produced by BM-derived podocytes
      integrates into the GBM and associates with other alpha-chains to form type IV
      collagen triple helical networks. This study demonstrates that BM-derived stem
      cells can offer a viable strategy for repairing basement membrane defects and
      conferring therapeutic benefit for patients with Alport syndrome.

PMID- 16648257
TI  - Dimerization and interactions of Brucella suis VirB8 with VirB4 and VirB10 are
      required for its biological activity.
AB  - VirB8-like proteins are essential components of type IV secretion systems,
      bacterial virulence factors that mediate the translocation of effector molecules
      from many bacterial pathogens into eukaryotic cells. Based on cell biological,
      genetic, and x-ray crystallographic data, VirB8 was proposed to undergo multiple
      protein-protein interactions to mediate assembly of the translocation machinery.
      Here we report the results of a structure-function analysis of the periplasmic
      domain of VirB8 from the mammalian pathogen Brucella suis, which identifies amino
      acid residues required for three protein-protein interactions. VirB8 variants
      changed at residues proposed to be involved in dimerization, and protein-protein
      interactions were purified and characterized in vitro and in vivo. Changes at
      M102, Y105, and E214 affected the self-association as measured by analytical
      ultracentrifugation and gel filtration. The interaction with B. suis VirB10 was
      reduced by changes at T201, and change at R230 inhibited the interaction with
      VirB4 in vitro. The in vivo functionality of VirB8 variants was determined by
      complementation of growth in macrophages by a B. suis virB8 mutant and by using a
      heterologous assay of type IV secretion system assembly in Agrobacterium
      tumefaciens. Changes at Y105, T201, R230, and at several other residues impaired
      the in vivo function of VirB8, suggesting that we have identified interaction
      sites of relevance in the natural biological context.

PMID- 16648258
TI  - Behavioral sensitization to amphetamine results from an uncoupling between
      noradrenergic and serotonergic neurons.
AB  - In rodents, drugs of abuse induce locomotor hyperactivity, and repeating
      injections enhances this response. This effect, called behavioral sensitization,
      persists many months after the last administration, thus mimicking long-term
      sensitivity to drugs observed in human addicts. We show here that, in naive
      animals, noradrenergic and serotonergic systems, besides their behavioral
      activating effects, inhibit each other by means of the stimulation of alpha1b
      adrenergic and 5-HT(2A) receptors and that this mutual inhibition vanishes with
      repeated injections of d-amphetamine; this uncoupling may be responsible for
      behavioral sensitization and for an increased reactivity of dopaminergic neurons.
      First, after repeated d-amphetamine injections, a d-amphetamine challenge induces
      a dramatic increase in cortical extracellular norepinephrine (NE) levels. This
      increased cortical NE release still occurs after 1 month of withdrawal but is
      diminished or blocked if sensitization is performed in the presence of prazosin,
      SR46349B, or both alpha1-adrenergic and 5-HT(2A) receptor antagonists,
      respectively. A strong correlation between increases in cortical extracellular NE
      levels and the expression of behavioral sensitization was found. Second, repeated
      d-amphetamine injections induce an increased reactivity of serotonergic neurons
      measured by cortical extracellular serotonin (5-HT) levels after the
      administration of a 5-HT releaser, p-chloroamphetamine. Third, knockout mice for
      alpha1b-adrenergic (alpha1b-AR KO) or 5-HT(2A) (5-HT(2A)-R KO) receptor,
      respectively, exhibit a behavioral and biochemical hyperreactivity to the acute
      injection of p-chloroamphetamine (alpha1b-AR KO; 5-HT levels) and d-amphetamine
      (5-HT(2A)-R KO; NE levels). Uncoupling between noradrenergic and serotonergic
      neurons may occur not only in addiction but also during chronic stressful
      situations, thus facilitating the onset of mental illness.

PMID- 16648259
TI  - Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts
      retroviral infection.
AB  - Primate tripartite motif 5alpha (TRIM5alpha) proteins mediate innate
      intracellular resistance to retroviruses. In humans, TRIM5 is located in a
      paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and
      TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified
      only in primates. Cow cells exhibit early blocks to infection by several
      retroviruses. We identify a cytoplasmic TRIM protein encoded by LOC505265 that is
      responsible for the restriction of infection by several lentiviruses and N-tropic
      murine leukemia virus in cow cells. Susceptibility of N-tropic murine leukemia
      virus to 505265-mediated restriction is determined primarily by residue 110 of
      the viral capsid protein. Phylogenetically, cow LOC505265 segregates with the
      TRIM5/TRIM6/TRIM34 group, but is not an ortholog of known TRIM genes. The
      B30.2/SPRY domain of 505265 exhibits long variable regions, a characteristic of
      the proteins encoded by this paralogous group, and shows evidence of positive
      selection. Apparently, cows have independently evolved a retroviral restriction
      factor from the same TRIM family that spawned TRIM5 in primates. Particular
      features of this subset of cytoplasmic TRIM proteins may be conducive to the
      convergent evolution of virus-restricting factors.

PMID- 16648260
TI  - Identification of S-nitrosylation motifs by site-specific mapping of the S
      nitrosocysteine proteome in human vascular smooth muscle cells.
AB  - S-nitrosylation, the selective modification of cysteine residues in proteins to
      form S-nitrosocysteine, is a major emerging mechanism by which nitric oxide acts
      as a signaling molecule. Even though nitric oxide is intimately involved in the
      regulation of vascular smooth muscle cell functions, the potential protein
      targets for nitric oxide modification as well as structural features that
      underlie the specificity of protein S-nitrosocysteine formation in these cells
      remain unknown. Therefore, we used a proteomic approach using selective peptide
      capturing and site-specific adduct mapping to identify the targets of S
      nitrosylation in human aortic smooth muscle cells upon exposure to S
      nitrosocysteine and propylamine propylamine NONOate. This strategy identified 20
      unique S-nitrosocysteine-containing peptides belonging to 18 proteins including
      cytoskeletal proteins, chaperones, proteins of the translational machinery,
      vesicular transport, and signaling. Sequence analysis of the S-nitrosocysteine
      containing peptides revealed the presence of acid/base motifs, as well as
      hydrophobic motifs surrounding the identified cysteine residues. High-resolution
      immunogold electron microscopy supported the cellular localization of several of
      these proteins. Interestingly, seven of the 18 proteins identified are localized
      within the ER/Golgi complex, suggesting a role for S-nitrosylation in membrane
      trafficking and ER stress response in vascular smooth muscle.

PMID- 16648261
TI  - Nonconscious semantic processing of emotional words modulates conscious access.
AB  - Whether masked words can be processed at a semantic level remains a controversial
      issue in cognitive psychology. Although recent behavioral studies have
      demonstrated masked semantic priming for number words, attempts to generalize
      this finding to other categories of words have failed. Here, as an alternative to
      subliminal priming, we introduce a sensitive behavioral method to detect
      nonconscious semantic processing of words. The logic of this method consists of
      presenting words close to the threshold for conscious perception and examining
      whether their semantic content modulates performance in objective and subjective
      tasks. Our results disclose two independent sources of modulation of the
      threshold for access to consciousness. First, prior conscious perception of words
      increases the detection rate of the same words when they are subsequently
      presented with stronger masking. Second, the threshold for conscious access is
      lower for emotional words than for neutral ones, even for words that have not
      been previously consciously perceived, thus implying that written words can
      receive nonconscious semantic processing.

PMID- 16648262
TI  - Functional differences between galactolipids and glucolipids revealed in
      photosynthesis of higher plants.
AB  - Galactolipids represent the most abundant lipid class in thylakoid membranes,
      where oxygenic photosynthesis is performed. The identification of galactolipids
      at specific sites within photosynthetic complexes by x-ray crystallography
      implies specific roles for galactolipids during photosynthetic electron
      transport. The preference for galactose and not for the more abundant sugar
      glucose in thylakoid lipids and their specific roles in photosynthesis are not
      understood. Introduction of a bacterial glucosyltransferase from Chloroflexus
      aurantiacus into the galactolipid-deficient dgd1 mutant of Arabidopsis thaliana
      resulted in the accumulation of a glucose-containing lipid in the thylakoids. At
      the same time, the growth defect of the dgd1 mutant was complemented. However,
      the degree of trimerization of light-harvesting complex II and the photosynthetic
      quantum yield of transformed dgd1 plants were only partially restored. These
      results indicate that specific interactions of the galactolipid head group with
      photosynthetic protein complexes might explain the preference for galactose in
      thylakoid lipids of higher plants. Therefore, galactose in thylakoid lipids can
      be exchanged with glucose without severe effects on growth, but the presence of
      galactose is crucial to maintain maximal photosynthetic efficiency.

PMID- 16648263
TI  - Essential role of retinoblastoma protein in mammalian hair cell development and
      hearing.
AB  - The retinoblastoma protein pRb is required for cell-cycle exit of embryonic
      mammalian hair cells but not for their early differentiation. However, its role
      in postnatal hair cells is unknown. To study the function of pRb in mature
      animals, we created a new conditional mouse model, with the Rb gene deleted
      primarily in the inner ear. Progeny survive up to 6 months. During early
      postnatal development, pRb(-/-) hair cells continue to divide and can transduce
      mechanical stimuli. However, adult pRb(-/-) mice exhibit profound hearing loss
      due to progressive degeneration of the organ of Corti. We show that pRb is
      required for the full maturation of cochlear outer hair cells, likely in a gene
      specific manner, and is also essential for their survival. In addition, lack of
      pRb results in cell division in postnatal auditory supporting cells. In contrast,
      many pRb(-/-) vestibular hair cells survive and continue to divide in adult mice.
      Significantly, adult pRb(-/-) vestibular hair cells are functional, and pRb(-/-)
      mice maintain partial vestibular function. Therefore, the functional adult
      vestibular pRb(-/-) hair cells, derived from proliferation of postnatal hair
      cells, are largely integrated into vestibular pathways. This study reveals
      essential yet distinct roles of pRb in cochlear and vestibular hair cell
      maturation, function, and survival and suggests that transient block of pRb
      function in mature hair cells may lead to propagation of functional hair cells.

PMID- 16648264
TI  - Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse
      transcription and infection.
AB  - The primate TRIM5alpha proteins have recently been defined as cellular
      restriction factors, preventing primate infection by retroviruses from different
      species. For instance, rhesus TRIM5alpha (rhTRIM5alpha) restricts infection by
      HIV-1. Virtually all TRIM5alpha proteins block the early replication of
      retroviruses by preventing the accumulation of reverse transcription products,
      but the underlying mechanism remains unclear. In this article, we find that
      disrupting proteasome function alters rhTRIM5alpha localization and allows the
      normal generation of HIV-1 late reverse transcription products, even though HIV-1
      infection and the generation of nuclear 1-LTR and 2-LTR viral cDNA forms remain
      impaired. This finding suggests rhTRIM5alpha restricts HIV infection in two
      distinct phases: (i) altering the normal passage of the reverse-transcribing
      viral genome to the nucleus and (ii) targeting the reverse transcription complex
      to be disrupted by the proteasome. Because proteasome inhibitor blocks the second
      phase, accumulation of a nonfunctional viral DNA genome can be readily observed.
      Defining each phase may reveal HIV-1 targets for future antiviral therapy in
      which dual blockade may be equally as effective as naturally occurring
      rhTRIM5alpha protein in preventing HIV-1 infection in vivo.

PMID- 16648265
TI  - Flexibly varying folding mechanism of a nearly symmetrical protein: B domain of
      protein A.
AB  - The folding pathway of the B domain of protein A is the pathway most intensively
      studied by computer simulations. Recent systematic measurement of Phi values by
      Sato et al., however, has shown that none of the published computational
      predictions is consistent with the detailed features of the experimentally
      observed folding mechanism. In this article we use a statistical mechanical model
      of folding to show that sensitive dependence of multiple transition state
      ensembles on temperature and the denaturant concentration is the key to resolving
      the inconsistency among simulations and the experiment. Such sensitivity in
      multiple transition state ensembles is a natural consequence of symmetry-breaking
      in a nearly symmetrical protein.

PMID- 16648266
TI  - Predicting stochastic gene expression dynamics in single cells.
AB  - Fluctuations in protein numbers (noise) due to inherent stochastic effects in
      single cells can have large effects on the dynamic behavior of gene regulatory
      networks. Although deterministic models can predict the average network behavior,
      they fail to incorporate the stochasticity characteristic of gene expression,
      thereby limiting their relevance when single cell behaviors deviate from the
      population average. Recently, stochastic models have been used to predict
      distributions of steady-state protein levels within a population but not to
      predict the dynamic, presteady-state distributions. In the present work, we
      experimentally examine a system whose dynamics are heavily influenced by
      stochastic effects. We measure population distributions of protein numbers as a
      function of time in the Escherichia coli lactose uptake network (lac operon). We
      then introduce a dynamic stochastic model and show that prediction of dynamic
      distributions requires only a few noise parameters in addition to the rates that
      characterize a deterministic model. Whereas the deterministic model cannot fully
      capture the observed behavior, our stochastic model correctly predicts the
      experimental dynamics without any fit parameters. Our results provide a proof of
      principle for the possibility of faithfully predicting dynamic population
      distributions from deterministic models supplemented by a stochastic component
      that captures the major noise sources.

PMID- 16648267
TI  - Modulatory calcineurin-interacting proteins 1 and 2 function as calcineurin
      facilitators in vivo.
AB  - The calcium-activated phosphatase calcineurin is regulated by a binding cofactor
      known as modulatory calcineurin-interacting protein (MCIP) in yeast up through
      mammals. The physiologic function of MCIP remains an area of ongoing
      investigation, because both positive and negative calcineurin regulatory effects
      have been reported. Here we disrupted the mcip1 and mcip2 genes in the mouse and
      provide multiple lines of evidence that endogenous MCIP functions as a
      calcineurin facilitator in vivo. Mouse embryonic fibroblasts deficient in both
      mcip1/2 showed impaired activation of nuclear factor of activated T cells (NFAT),
      suggesting that MCIP is required for efficient calcineurin-NFAT coupling. Mice
      deficient in mcip1/2 showed a dramatic impairment in cardiac hypertrophy induced
      by pressure overload, neuroendocrine stimulation, or exercise, similar to mice
      lacking calcineurin Abeta. Moreover, simultaneous deletion of calcineurin Abeta
      in the mcip1/2-null background did not rescue impaired hypertrophic growth after
      pressure overload. Slow/oxidative fiber-type switching in skeletal muscle after
      exercise stimulation was also impaired in mcip1/2 mice, similar to calcineurin
      Abeta-null mice. Moreover, CD4(+) T cells from mcip1/2-null mice showed enhanced
      apoptosis that was further increased by loss of calcineurin Abeta. Finally,
      mcip1/2-null mice displayed a neurologic phenotype that was similar to
      calcineurin Abeta-null mice, such as increased locomotor activity and impaired
      working memory. Thus, a loss-of-function analysis suggests that MCIPs serve
      either a permissive or facilitative function for calcineurin-NFAT signaling in
      vivo.

PMID- 16648268
TI  - Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a
      South American population isolate.
AB  - Although it is well established that Hispanics generally have a mixed Native
      American, African, and European ancestry, the dynamics of admixture at the
      foundation of Hispanic populations is heterogeneous and poorly documented.
      Genetic analyses are potentially very informative for probing the early
      demographic history of these populations. Here we evaluate the genetic structure
      and admixture dynamics of a province in northwest Colombia (Antioquia), which
      prior analyses indicate was founded mostly by Spanish men and native women. We
      examined surname, Y chromosome, and mtDNA diversity in a geographically
      structured sample of the region and obtained admixture estimates with highly
      informative autosomal and X chromosome markers. We found evidence of reduced
      surname diversity and support for the introduction of several common surnames by
      single founders, consistent with the isolation of Antioquia after the colonial
      period. Y chromosome and mtDNA data indicate little population substructure among
      founder Antioquian municipalities. Interestingly, despite a nearly complete
      Native American mtDNA background, Antioquia has a markedly predominant European
      ancestry at the autosomal and X chromosome level, which suggests that, after
      foundation, continuing admixture with Spanish men (but not with native women)
      increased the European nuclear ancestry of Antioquia. This scenario is consistent
      with historical information and with results from population genetics theory.

PMID- 16648269
TI  - Energy landscape view of phase transitions and slow dynamics in thermotropic
      liquid crystals.
AB  - Thermotropic liquid crystals are known to display rich phase behavior on
      temperature variation. Although the nematic phase is orientationally ordered but
      translationally disordered, a smectic phase is characterized by the appearance of
      a partial translational order in addition to a further increase in orientational
      order. In an attempt to understand the interplay between orientational and
      translational order in the mesophases that thermotropic liquid crystals typically
      exhibit upon cooling from the high-temperature isotropic phase, we investigate
      the potential energy landscapes of a family of model liquid crystalline systems.
      The configurations of the system corresponding to the local potential energy
      minima, known as the inherent structures, are determined from computer
      simulations across the mesophases. We find that the depth of the potential energy
      minima explored by the system along an isochor grows through the nematic phase as
      temperature drops in contrast to its insensitivity to temperature in the
      isotropic and smectic phases. The onset of the growth of the orientational order
      in the parent phase is found to induce a translational order, resulting in a
      smectic-like layer in the underlying inherent structures; the inherent
      structures, surprisingly, never seem to sustain orientational order alone if the
      parent nematic phase is sandwiched between the high-temperature isotropic phase
      and the low-temperature smectic phase. The Arrhenius temperature dependence of
      the orientational relaxation time breaks down near the isotropic-nematic
      transition. We find that this breakdown occurs at a temperature below which the
      system explores increasingly deeper potential energy minima.

PMID- 16648270
TI  - Localization of cardiac L-type Ca(2+) channels to a caveolar macromolecular
      signaling complex is required for beta(2)-adrenergic regulation.
AB  - L-type Ca(2+) channels play a critical role in regulating Ca(2+)-dependent
      signaling in cardiac myocytes, including excitation-contraction coupling;
      however, the subcellular localization of cardiac L-type Ca(2+) channels and their
      regulation are incompletely understood. Caveolae are specialized microdomains of
      the plasmalemma rich in signaling molecules and supported by the structural
      protein caveolin-3 in muscle. Here we demonstrate that a subpopulation of L-type
      Ca(2+) channels is localized to caveolae in ventricular myocytes as part of a
      macromolecular signaling complex necessary for beta(2)-adrenergic receptor (AR)
      regulation of I(Ca,L). Immunofluorescence studies of isolated ventricular
      myocytes using confocal microscopy detected extensive colocalization of caveolin
      3 and the major pore-forming subunit of the L-type Ca channel (Ca(v)1.2).
      Immunogold electron microscopy revealed that these proteins colocalize in
      caveolae. Immunoprecipitation from ventricular myocytes using anti-Ca(v)1.2 or
      anti-caveolin-3 followed by Western blot analysis showed that caveolin-3,
      Ca(v)1.2, beta(2)-AR (not beta(1)-AR), G protein alpha(s), adenylyl cyclase,
      protein kinase A, and protein phosphatase 2a are closely associated. To determine
      the functional impact of the caveolar-localized beta(2)-AR/Ca(v)1.2 signaling
      complex, beta(2)-AR stimulation (salbutamol plus atenolol) of I(Ca,L) was
      examined in pertussis toxin-treated neonatal mouse ventricular myocytes. The
      stimulation of I(Ca,L) in response to beta(2)-AR activation was eliminated by
      disruption of caveolae with 10 mM methyl beta-cyclodextrin or by small
      interfering RNA directed against caveolin-3, whereas beta(1)-AR stimulation
      (norepinephrine plus prazosin) of I(Ca,L) was not altered. These findings
      demonstrate that subcellular localization of L-type Ca(2+) channels to caveolar
      macromolecular signaling complexes is essential for regulation of the channels by
      specific signaling pathways.

PMID- 16648271
TI  - Weaponising medicine: "Tutti fratelli," no more.

PMID- 16648272
TI  - Phase I oncology trials: why the therapeutic misconception will not go away.

PMID- 16648273
TI  - Boundaries, borders, and limits. A phenomenological reflection on ethics and
      euthanasia.
AB  - The subject of euthanasia divides both people and nations. It will always
      continue to do so because the arguments for and against this issue are
      intrinsically related to each other. This paper offers an analysis of the
      interrelation of the arguments, departing from a phenomenology of boundaries.
      From the participant perspective the boundary of euthanasia appears as a limit.
      From a helicopter perspective it appears as a border. Reflecting on both
      perspectives they turn out to complement each other: the positive effects of the
      former correspond to the negative effects of the latter. In order to see how this
      interrelation of viewpoints works out in the case of euthanasia a paradigmatic
      case is analysed from the perspective of the patient, the doctor, and the family.
      This phenomenological analysis does not directly lead to normative conclusions.
      It helps by both paying attention to, and dealing with, the complexity of the
      issue with intellectual honesty.

PMID- 16648274
TI  - Are patients morally responsible for their errors?
AB  - Amid neglect of patients' contribution to error has been a failure to ask whether
      patients are morally responsible for their errors. This paper aims to help answer
      this question and so define a worthy response to the errors. Recent work on
      medical errors has emphasised system deficiencies and discouraged finding people
      to blame. We scrutinize this approach from an incompatibilist, agent causation
      position and draw on Hart's taxonomy of four senses of moral responsibility: role
      responsibility; capacity responsibility; causal responsibility; and liability
      responsibility. Each sense is shown to contribute to an overall theoretical
      judgment as to whether patients are morally responsible for their errors (and
      success in avoiding them). Though how to weight the senses is unclear, patients
      appear to be morally responsible for the avoidable errors they make, contribute
      to or can influence.

PMID- 16648275
TI  - When alcohol abstinence criteria create ethical dilemmas for the liver transplant
      team.

PMID- 16648276
TI  - Trends in public approval of euthanasia and suicide in the US, 1947-2003.

PMID- 16648277
TI  - Informed choice of pregnant women in prenatal screening tests for Down's
      syndrome.
AB  - BACKGROUND: Although maternal serum screening (MSS) for Down's syndrome has
      become routinely available in most obstetric clinics in many countries, few
      studies have addressed the reasons why women agree to undergo the MSS test.
      OBJECTIVES: The aims of this study were to describe the circumstances in which
      MSS was offered to pregnant women and their reasons for undertaking it. METHODS:
      Participant observation and in depth interviews were used in this study;
      specifically, the experiences of women who had a positive result for MSS and who
      then followed this up with amniocentesis were examined. The interviewees were
      twenty six mothers aged between 22 and 35 years. The interviews were audio taped
      and transcribed for analysis. The results were analysed by the constant
      comparative method. RESULTS: This study identified the reasons on which pregnant
      women appeared to base their decisions when undergoing MSS. The reasons were
      first, the recognition that the procedure was a prenatal routine procedure;
      second, the need to avoid the risk of giving birth to a baby with Down's
      syndrome, and third, a trust in modern technology and in the professional
      authorities. CONCLUSIONS: This study offers insights into the informed choice
      made by women with a positive MSS result. The reasons for undergoing MSS might
      help health professionals and policy makers to reflect on their practice and this
      may, in turn, improve the quality of prenatal care during MSS.

PMID- 16648278
TI  - Britain's new preimplantation tissue typing policy: an ethical defence.

PMID- 16648279
TI  - The UK Human Tissue Act and consent: surrendering a fundamental principle to
      transplantation needs?

PMID- 16648280
TI  - Women's reproductive autonomy: medicalisation and beyond.
AB  - Reproductive autonomy is central to women's welfare both because childbearing
      takes place in women's bodies and because they are generally expected to take
      primary responsibility for child rearing. In 2005, the factors that influence
      their autonomy most strongly are poverty and belief systems that devalue such
      autonomy. Unfortunately, such autonomy is a low priority for most societies, or
      is anathema to their belief systems altogether. This situation is doubly sad
      because women's reproductive autonomy is intrinsically valuable for women and
      also instrumentally valuable for the welfare of humankind. This paper takes for
      granted the moral and practical necessity of such autonomy and digs deeper into
      the question of what such a commitment might entail, focusing on the mid-level
      policy making that, at least in the US and Canada, plays a significant role in
      shaping women's options. This paper examines a large teaching hospital's policy
      on reduction of multifetal pregnancies. The policy permits reduction of triplets
      to twins, but not twins to a singleton. As there is no morally relevant
      difference between these two types of reduction, it is evident that inappropriate
      medicalisation can still limit women's autonomy in undesirable ways.

PMID- 16648281
TI  - A questionnaire on factors influencing children's assent and dissent to non
      therapeutic research.
AB  - BACKGROUND: Knowledge about assent or dissent of children to non-therapeutic
      research is poor. OBJECTIVES: To assess sociodemographic characteristics in
      healthy children and adolescents who were invited to participate in non
      therapeutic research, to evaluate their motives for assent or dissent and their
      understanding of the information given. METHODS: A total of 1281 healthy children
      and adolescents six to sixteen years of age were invited to participate in a non
      therapeutic study and a questionnaire. RESULTS: Assenting children were motivated
      by a desire to help sick children (n = 638, 98%) and to gain experience with
      participating in a research study (n = 503, 82%). Dissenting children made their
      decision because of worries about having a blood (n = 193, 46%) or a urine sample
      (n = 94, 26%) taken or because of worries about a doctor's examination (n = 136,
      33%). Fewer children in the assent group (n = 166, 25%) than in the dissent group
      (136, 33%) worried about the doctor's examination (p = 0.01). In the assent and
      dissent group, 568 (86%) and 343 (85%) children, respectively, said they were
      able to understand some or all of the written information (p = 0.42), and 650
      (97%) and 330 (98%), respectively, were able to understand some or all of the
      verbal information (p = 0.07). CONCLUSIONS: Sociodemographic characteristics may
      not influence healthy children's decision to volunteer for non-therapeutic
      research. Assenting children have altruistic and educational motives, whereas
      worries about procedures may cause children to dissent. A great majority of
      school children and adolescents feel capable of understanding and giving assent
      or dissent to non-therapeutic research.

PMID- 16648282
TI  - Why the apparent haste to clone humans?

PMID- 16648283
TI  - How do bioethics teachers in Japan cope with ethical disagreement among
      healthcare university students in the classroom? A survey on educators in charge.
AB  - OBJECTIVE: The purpose of this study was to demonstrate how educators involved in
      the teaching of bioethics to healthcare university students in Japan would cope
      with ethical disagreement in the classroom, and to identify factors influencing
      them. METHODS: A cross sectional survey was conducted using self administered
      questionnaires mailed to a sample of university faculty in charge of bioethics
      curriculum for university healthcare students. RESULTS: A total of 107 usable
      questionnaires were returned: a response rate of 61.5%. When facing ethical
      disagreement in the classroom, coping behaviour differed depending on the topic
      of discussion, was influenced by educators' individual clear ethical attitudes
      regarding the topic of discussion, and was independent of many respondents'
      individual and social backgrounds. Among educators, it was commonly recognised
      that the purpose of bioethics education was to raise the level of awareness of
      ethical problems, to provide information about and knowledge of those issues, to
      raise students' sensitivity to ethical problems, and to teach students methods of
      reasoning and logical argument. Yet, despite this, several respondents considered
      the purpose of bioethics education to be to influence students about normative
      ethical judgments. There was no clear relationship, however, between ways of
      coping with ethical disagreement and educators' sense of the purpose of bioethics
      education. CONCLUSIONS: This descriptive study suggests that educators involved
      in bioethics education for healthcare university students in Japan coped in
      various ways with ethical disagreement. Further research concerning ethical
      disagreement in educational settings is needed to provide better bioethics
      education for healthcare students.

PMID- 16648286
TI  - Prolactin inhibits the apoptosis of chondrocytes induced by serum starvation.
AB  - The apoptosis of chondrocytes plays an important role in endochondral bone
      formation and in cartilage degradation during aging and disease. Prolactin (PRL)
      is produced in chondrocytes and is known to promote the survival of various cell
      types. Here we show that articular chondrocytes from rat postpubescent and adult
      cartilage express the long form of the PRL receptor as revealed by
      immunohistochemistry of cartilage sections and by RT-PCR and Western blot
      analyses of the isolated chondrocytes. Furthermore, we demonstrate that PRL
      inhibits the apoptosis of these same chondrocytes cultured in low-serum.
      Chondrocyte apoptosis was measured by hypodiploid DNA content determined by flow
      cytometry and by DNA fragmentation evaluated by the ELISA and the TUNEL methods.
      The anti-apoptotic effect of PRL was dose-dependent and was prevented by heat
      inactivation. These data demonstrate that PRL can act as a survival factor for
      chondrocytes and that it has potential preventive and therapeutic value in
      arthropathies characterized by cartilage degradation.

PMID- 16648287
TI  - Thyroid hormone and astrocyte morphogenesis.
AB  - Astrocyte cells clearly play a role in neural development, but nowadays their
      total action is seen as a far wider one. Recent findings consider them as stem
      cells, involved in the control of most facets of functional neural networks.
      Astrocytes play a central role in thyroid hormone metabolism in the brain, being
      the principal transporters of thyroxine from the blood, responsible for its
      conversion to 3,5,3'-triiodothyronine and hence supplying the neural tissues with
      the biologically active form of the hormone. Specific thyroid hormone
      transporters play an essential role in this regulatory system. The presence of
      thyroid hormone receptors has been demonstrated in cultured astrocytes.
      Furthermore, thyroid hormone regulates several aspects of astrocyte
      differentiation and maturation, including the production of extracellular matrix
      proteins and growth factors, and thus controls neuronal growth and
      neuritogenesis. Therefore, astrocytes are currently suggested as important
      mediators of thyroid hormone in neuronal development.

PMID- 16648288
TI  - Peroxisome proliferator-activated receptors in reproductive tissues: from
      gametogenesis to parturition.
AB  - Peroxisome proliferator-activated receptors (PPARalpha, PPARbeta/delta and
      PPARgamma) are a family of nuclear receptors that are activated by binding of
      natural ligands, such as polyunsaturated fatty acids or by synthetic ligands.
      Synthetic molecules of the glitazone family, which bind to PPARgamma, are
      currently used to treat type II diabetes and also to attenuate the secondary
      clinical symptoms frequently associated with insulin resistance, including
      polycystic ovary syndrome (PCOS). PPARs are expressed in different compartments
      of the reproductive system (hypothalamus, pituitary, ovary, uterus and testis).
      Conservative functions of PPARs in mammalian species could be suggested through
      several in vivo and in vitro studies, especially in the ovary and during
      placental development. Several groups have described a strong expression of
      PPARgamma in ovarian granulosa cells, and glitazones modulate granulosa cell
      proliferation and steroidogenesis in vitro. All these recent data raise new
      questions about the biologic actions of PPARs in reproduction and their use in
      therapeutic treatments of fertility troubles such as PCOS or endometriosis. In
      this review, we first describe the roles of PPARs in different compartments of
      the reproductive axis (from male and female gametogenesis to parturition), with a
      focus on PPARgamma. Secondly, we discuss the possible molecular mechanisms
      underlying the effect of glitazones on PCOS. Like other 'insulin sensitizer'
      molecules, such as metformin, glitazones may in fact act directly on ovarian
      cells. Finally, we discuss the eventual actions of PPARs as mediators of
      environmental toxic substances for reproductive function.

PMID- 16648289
TI  - Intra-adrenal mechanisms in the response to chronic stress: investigation in a
      rat model of emotionality.
AB  - The exploratory behaviour of the genetically derived Maudsley rat model of
      emotionality has been well characterized. Maudsley reactives (MR) present with
      more 'anxious-like' behaviour than Maudsley nonreactives (MNR). Although this
      behaviour is assumed to be associated with altered adrenocortical function, the
      few studies addressing this issue have produced inconsistent findings. We
      therefore set out to investigate the adrenal endocrinology of the MR and MNR
      strains. Control Wistars, the ancestors of the Maudsleys, have been used for the
      first time to set the baseline for all the experiments carried out. It was found
      that the MNR strain had a significantly blunted adrenocorticotrophic hormone
      (ACTH) response to restraint stress compared with Wistars, but a normal
      corticosterone response. Conversely, the MR had a significantly exaggerated ACTH
      response to restraint stress, but a normal corticosterone response. This finding
      suggested that the MR adrenal is less sensitive to ACTH than the MNR. This was
      confirmed by investigating the corticosterone dose-response to ACTH in adrenals
      from the two strains incubated in vitro. Several possible intra-adrenal
      regulators were investigated, but the only significant molecular difference in
      the adrenal glands from the two strains was the level of expression of
      neuropeptide Y (NPY), which is known to be a stress-responsive peptide in the
      adrenal. We propose that intra-adrenal NPY is responsible for blunting
      adrenocortical responses to ACTH stimulation in the MR strain. The observed
      changes in adrenal NPY suggest that this rat strain may serve as a model of
      chronic stress, with the MR phenotype representing maladaptation.

PMID- 16648290
TI  - Skeletal muscle glucose transporter protein responses to antenatal
      glucocorticoids in the ovine fetus.
AB  - We investigated the effects of maternal antenatal dexamethasone (Dex) treatment
      given as a single course (4 doses) or multiple courses (20 doses) on fetal
      skeletal muscle glucose transporter (GLUT) protein concentrations at 70% of
      gestation (106 to 107 days with term being 145 to 150 days) in the ovine fetus.
      Antenatal corticosteroid administration was associated with a decrease in
      endogenous fetal plasma cortisol concentrations (P < 0.05), fetal hyperglycemia
      (P < 0.02) and hyperinsulinemia (P < 0.05). These metabolic/hormonal changes were
      associated with a decrease in fetal body weight (P < 0.05) in the multiple course
      Dex group compared with the multiple course placebo group. These perturbations
      were associated with an increase in fetal skeletal muscle GLUT 1 concentrations
      that mediate basal glucose transport in the extensor digitorum lateralis and
      extensor digitorum longus muscles (P < 0.05) 18 h after the last dose of Dex was
      given in the single course group. However, in the multiple course Dex group, a
      small increase in GLUT 1 was observed only in the biceps femoris. In contrast,
      both single and multiple courses of antenatal Dex were associated with an
      increase in the extensor digitorum lateralis and biceps femoris muscle GLUT 4
      (insulin-responsive) concentrations (P < 0.05). We conclude that antenatal
      corticosteroids perturb fetal glucose/insulin homeostasis, which is associated
      with increases in fetal skeletal muscle glucose transporters to compensate for
      and attenuate the associated catabolic fetal state. These changes consist of an
      increase in proteins that mediate basal glucose transport (GLUT 1) to meet
      immediate energy requirements of the fetal skeletal muscle with an increase in
      basal insulin sensitivity (GLUT 4) to compensate for the Dex-induced catabolic
      state after exposure to multiple courses of Dex.

PMID- 16648291
TI  - Expression pattern and ontogenesis of thyroid hormone receptor isoforms in the
      mouse heart.
AB  - Nuclear thyroid hormone (T3) receptors (TR) play a critical role in mediating the
      effects of T3 on development, differentiation and normal physiology of many
      organs. The heart is a major target organ of T3, and recent studies in knockout
      mice demonstrated distinct effects of the different TR isoforms on cardiac
      function, but the specific actions of TR isoforms and their specific localization
      in the heart remain unclear. We therefore studied the expression of TRalpha1,
      TRalpha2 and TRbeta1 isoforms in the mouse heart at different stages of
      development, using monoclonal antibodies against TRalpha1, TRalpha2 and TRbeta1.
      In order to identify distinct components of the embryonic heart, in situ
      hybridization for cardiac-specific markers was used with the expression pattern
      of sarcoplasmic reticulum calcium-ATPase 2a as a marker of myocardial structures,
      while the pattern of expression of connexin40 was used to indicate the developing
      chamber myocardium and peripheral ventricular conduction system. Here we show
      that in the ventricles of the adult heart the TRbeta1 isoform is confined to the
      cells that form the peripheral ventricular conduction system. TRalpha1, on the
      other hand, is present in working myocardium as well as in the peripheral
      ventricular conduction system. In the atria and in the proximal conduction system
      (sinoatrial node, atrio-ventricular node), TRalpha1 and TRbeta1 isoforms are co
      expressed. We also found the heterogeneous expression of the TRalpha1, TRalpha2
      and TRbeta1 isoforms in the developing mouse heart, which, in the case of the
      TRbeta1 isoform, gradually revealed a dynamic expression pattern. It was present
      in all cardiomyocytes at the early stages of cardiogenesis, but from embryonic
      day 11.5 and into adulthood, TRbeta1 demonstrated a gradual confinement to the
      peripheral ventricular conduction system (PVCS), suggesting a specific role of
      this isoform in the formation of PVCS. Detailed knowledge of the distribution of
      TRalpha1 and TRbeta1 in the heart is of importance for understanding not only
      their mechanism of action in the heart but also the design and (clinical) use of
      TR isoform-specific agonists and antagonists.

PMID- 16648292
TI  - Differential regulation of apical and basal iodide transporters in the thyroid by
      thyroglobulin.
AB  - We have shown that thyroglobulin (Tg) is a potent autocrine regulator of thyroid
      specific gene expression, and proposed that the accumulated follicular Tg within
      the colloid is a major factor in determining follicular function. In the present
      report, we examined the effect of Tg on the action of TSH/cAMP and iodine with
      special focus on the regulation of basolateral and apical iodide transporters;
      the sodium/iodide symporter (NIS) and the pendred syndrome gene (PDS) by Tg. We
      show that expression of NIS and PDS are differentially regulated by Tg
      concentration and exposure time. In addition, we found that PDS gene was induced
      by TSH/cAMP and iodide in the presence of Tg. Based on these results, we propose
      a model for the physiological turnover of follicular function that is dynamically
      regulated by Tg.

PMID- 16648293
TI  - Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced
      multiple organ damage in rats.
AB  - The objective of this study was to examine the potential radioprotective
      properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative
      organ damage induced by irradiation. Sprague-Dawley rats were pre-treated with
      saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body
      irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to
      irradiation, while another group was followed for 72 h after irradiation, during
      which saline or PTU injections were repeated once daily. Lung, liver, kidney and
      ileum samples were obtained for the determination of malondialdehyde (MDA; an
      index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels,
      myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and
      collagen contents, while oxidant-induced DNA fragmentation was evaluated in the
      ileal tissues. All tissues were also examined microscopically and assayed for the
      production of reactive oxidants using chemiluminescence (CL). Lactate
      dehydrogenase (LDH), an indicator of tissue damage, and tumour necrosis factor
      alpha (TNFalpha) were assayed in serum samples. Irradiation caused a significant
      decrease in GSH level, which was accompanied by significant increases in MDA
      levels, MPO activity, CL levels and collagen content of the tissues studied
      (P<0.05-0.001). Similarly, serum TNFalpha and LDH were elevated in the irradiated
      rats as compared with the control group. On the other hand, PTU treatment
      reversed all these biochemical indices, as well as histopathological alterations
      induced by irradiation. Our results suggested that PTU-induced hypothyroidism
      reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably
      due to hypometabolism, which is associated with decreased production of reactive
      oxygen metabolites and enhancement of antioxidant mechanisms.

PMID- 16648294
TI  - Increasing plasma thyroxine levels during late embryogenesis and hatching in the
      chicken are not caused by an increased sensitivity of the thyrotropes to
      hypothalamic stimulation.
AB  - The hatching process in the chicken is accompanied by dramatic changes in plasma
      thyroid hormones. The cause of these changes, though crucial for hatching and the
      onset of endothermy, is not known. One hypothesis is that the pituitary gland
      becomes more sensitive to hypothalamic stimulation during this period. We have
      tested whether the responsiveness of the thyrotropes to hypothalamic stimuli
      changes throughout the last week of embryonic development and hatching by
      studying the mRNA expression of receptors involved in the control of the
      secretory activity of this cell type. We used a real-time PCR set-up to quantify
      whole pituitary mRNA expression of the beta subunit of thyrotrophin (TSH-beta),
      type 1 thyrotrophin-releasing hormone receptor (TRH-R1), corticotrophin-releasing
      hormone receptors (CRH-R1 and CRH-R2) and somatostatin subtype receptor 2 (SSTR2)
      on every day of the last week of embryonic development, including the day of
      hatch and the first day of posthatch life. The thyrotrope-specific expression was
      investigated by a combination of in situ hybridization with immunohistochemistry
      at selected ages. Although TSH-beta mRNA levels increased towards day 19 of
      incubation (E19), the expression of CRH-R2 and TRH-R1 mRNA by the thyrotropes
      tended to decrease during this period, suggesting a lower sensitivity of the
      thyrotropes to the stimulatory factors CRH and TRH. CRH-R1, which is not involved
      in the control of TSH secretion, increased steadily throughout the period tested.
      The expression of SSTR2 mRNA by the thyrotropes was low during embryonic
      development and increased just before hatching. We have concluded that the
      sensitivity of the pituitary thyrotropes to hypothalamic stimulation decreases
      throughout the last week of embryonic development, so that the higher expression
      of TSH-beta mRNA around E16-E19, and hence the increasing plasma thyroxine level,
      is unlikely to be the result of an increased stimulation by either TRH or CRH.

PMID- 16648295
TI  - Gender differences in the response of CD-1 mouse bone to parathyroid hormone:
      potential role of IGF-I.
AB  - Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone.
      Studies on the skeletal effects of PTH have seldom considered the effects of
      gender. Our study was designed to determine whether the response of mouse bone to
      PTH differed according to sex. As a first step, we analyzed gender differences
      with respect to bone mass and structural properties of 4 month old PTH treated
      (80 microg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly
      increased fat free weight/body weight, periosteal bone formation rate, mineral
      apposition rate, and endosteal single labeling surface, while significantly
      decreasing medullary area in male mice compared with vehicle treated controls,
      but induced no significant changes in female mice. We then analyzed the gender
      differences in bone marrow stromal cells (BMSC) isolated from 4 month old male
      and female CD-1 mice following treatment with PTH (80 microg/kg per day for 2
      weeks). PTH significantly increased the osteogenic colony number and the alkaline
      phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male
      and female mice. PTH also increased the mRNA level of receptor activator of
      nuclear factor kappaB ligand in the bone tissue (marrow removed) of both females
      and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the
      bones of male mice. Our results indicate that on balance a 2-weeks course of PTH
      is anabolic on cortical bone in this mouse strain. These effects are more evident
      in the male mouse. These differences between male and female mice may reflect the
      greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing
      the anabolic effect on cortical bone.

PMID- 16648296
TI  - The ternary IGF complex influences postnatal bone acquisition and the skeletal
      response to intermittent parathyroid hormone.
AB  - The role of circulating IGF-I in skeletal acquisition and the anabolic response
      to PTH is not well understood. We generated IGF-I-deficient mice by gene
      deletions of IGF ternary complex components including: (1) liver-specific
      deletion of the IGF-I gene (LID), (2) global deletion of the acid-labile (ALS)
      gene (ALSKO), and (3) both liver IGF-I and ALS inactivated genes (LA). Twelve
      week-old male control (CTL), LID, ALSKO, and LA mice were treated with vehicle
      (VEH) or human PTH(1-34) for 4 weeks. VEH-treated IGF-I-deficient mice (i.e. LID,
      ALSKO and LA mice) exhibited reduced cortical cross-sectional area (P = 0.001)
      compared with CTL mice; in contrast, femoral trabecular bone volume fractions
      (BV/TV) of the IGF-I-deficient mice were consistently greater than CTL (P <
      0.01). ALSKO mice exhibited markedly reduced osteoblast number and surface (P <
      0.05), as well as mineral apposition rate compared with other IGF-I-deficient and
      CTL mice. Adherent bone marrow stromal cells, cultured in beta-glycerol phosphate
      and ascorbic acid, showed no strain differences in secreted IGF-I. In response to
      PTH, there were both compartment- and strain-specific effects. Cortical bone area
      was increased by PTH in CTL and ALSKO mice, but not in LID or LA mice. In the
      trabecular compartment, PTH increased femoral and vertebral BV/TV in LID, but not
      in ALSKO or LA mice. In conclusion, we demonstrated that the presentation of IGF
      I as a circulating complex is essential for skeletal remodeling and the anabolic
      response to PTH. We postulate that the ternary complex itself, rather than IGF-I
      alone, influences bone acquisition in a compartment-specific manner (i.e.
      cortical vs trabecular bone).

PMID- 16648297
TI  - Detrimental actions of metabolic syndrome risk factor, homocysteine, on
      pancreatic beta-cell glucose metabolism and insulin secretion.
AB  - Elevated plasma homocysteine has been reported in individuals with diseases of
      the metabolic syndrome including vascular disease and insulin resistance. As
      homocysteine exerts detrimental effects on endothelial and neuronal cells, this
      study investigated effects of acute homocysteine exposure on beta-cell function
      and insulin secretion using clonal BRIN-BD11 beta-cells. Acute insulin release
      studies in the presence of various test reagents were performed using monolayers
      of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular
      glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis
      following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the
      absence or presence of homocysteine. Homocysteine dose-dependently inhibited
      insulin release at moderate and stimulatory glucose concentrations. This
      inhibitory effect was reversible at all but the highest concentration of
      homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from
      glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA)
      cycle-dependent glucose metabolism was reduced in the presence of homocysteine.
      Homocysteine also dose-dependently inhibited insulinotropic responses to a range
      of glucose-dependent secretagogues including nutrients (alanine, arginine, 2
      ketoisocaproate), hormones (glucagon-like peptide-1 (7-36)amide, gastric
      inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug
      (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+.
      Insulin secretion induced by activation of adenylate cyclase and protein kinase C
      pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited
      by homocysteine. These effects were not associated with any adverse action on
      cellular insulin content or cell viability, and there was no increase in
      apoptosis/necrosis following exposure to homocysteine. These data indicate that
      homocysteine impairs insulin secretion through alterations in beta-cell glucose
      metabolism and generation of key stimulus-secretion coupling factors. The
      participation of homocysteine in possible beta-cell demise merits further
      investigation.

PMID- 16648298
TI  - Enhanced expression of hexokinase I in pancreatic islets induced by sucrose
      administration.
AB  - Administration of a sucrose-rich diet (SRD) to normal hamsters induces an insulin
      resistant state and a significant increase of insulin secretion and beta-cell
      mass. Islets isolated from these animals had a marked increase in glucose
      metabolism and glucose-induced insulin secretion, at both low and high glucose
      concentrations. They also presented increased hexokinase (HK) activity, without
      measurable changes in glucokinase (GK) activity. In this study we measured HK and
      GK activity in homogenates of islets isolated from normal control and SRD-fed
      hamsters, as well as in their particulate and cytosolic fractions. We also
      measured transcription rate (mRNA by reverse transcriptase PCR) and expression
      levels (Western blotting) of both enzymes in these islets. We found an increase
      in HK activity and expression levels, without measurable changes in HK mRNA level
      in SRD-fed animals. Whereas a similar GK activity was measured in homogenates of
      islets isolated from both groups, such activity was significantly higher in the
      cytosolic fraction of SRD islets. On the other hand, GK transcription rate and
      expression level were similar in both experimental groups. Our results suggest
      that the increased beta-cell secretory response to low glucose can be partly
      ascribed to an increased activity of islet HK consecutive to an enhanced
      expression of the enzyme, while the enhanced response to high glucose could be
      due to changes in GK compartmentalization.

PMID- 16648299
TI  - The restricted potential for recovery of growth plate chondrogenesis and
      longitudinal bone growth following exposure to pro-inflammatory cytokines.
AB  - Childhood chronic inflammatory disease can be associated with transient and
      permanent growth retardation. This study examined the potential for spontaneous
      growth recovery following pro-inflammatory cytokine exposure. Murine ATDC5
      chondrogenic cells and postnatal metatarsals were exposed to interleukin (IL)
      1beta, IL-6 and tumour necrosis factor-alpha (TNFalpha), and their growth and
      proliferative capacity were determined following recovery. TNFalpha and IL-1beta
      reduced chondrocyte proliferation and aggrecan and collagen types II and X
      expression at minimum concentrations of 10 ng/ml and 0.1 ng/ml respectively.
      TNFalpha but not IL-1beta exposure led to increased caspase-3 activity and
      altered cellular morphology, consistent with reduced viability. Cytokine exposure
      particularly inhibited proteoglycan synthesis. This effect was dose and duration
      dependent. Compared with the control, IL-1beta and TNFalpha led to a 71% and 45%
      reduction in metatarsal growth after 8 days of exposure respectively (P < 0.05).
      An additive effect of IL-1beta combined with TNFalpha was observed (110%
      decrease; P < 0.05). Metatarsals exposed to IL-1beta or TNFalpha individually for
      a 2-day period, and allowed to recover spontaneously in the absence of cytokines
      for a further 6 days, showed normal growth trajectories. In combination, growth
      was 59% lower (P < 0.01) compared with control metatarsals at the end of the
      recovery period. Exposure to the combination for 4 days followed by a 4-day
      recovery period resulted in 87% decrement compared with controls (P < 0.05). IL-6
      did not alter any parameter studied. IL-1beta and TNFalpha exert diverse
      inhibitory effects on ATDC5 chondrocyte dynamics and metatarsal growth. The
      extent of recovery following cytokine exposure depends on the duration of
      exposure, and may be incomplete following longer periods of exposure.

PMID- 16648300
TI  - Growth differentiation factor-9 has divergent effects on proliferation and
      steroidogenesis of bovine granulosa cells.
AB  - In addition to gonadotropins, steroidogenesis and proliferation of granulosa
      cells during follicular development are controlled by a number of intraovarian
      factors including growth differentiation factor-9 (GDF-9), bone morphogenetic
      protein-4 (BMP-4), and IGF-I. The objective of this study was to determine the
      effect of GDF-9 and BMP-4 and their interaction with IGF-I and FSH on ovarian
      granulosa cell function in cattle. Granulosa cells from small (1-5 mm) and large
      (8-22 mm) follicles were collected from bovine ovaries and cultured for 48 h in
      medium containing 10% fetal calf serum and then treated with various hormones in
      serum-free medium for an additional 48 h. We evaluated the effects of GDF-9 (150
      600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced
      steroidogenesis and cell proliferation. In FSH plus IGF-I-treated granulosa cells
      obtained from small follicles, 300 ng/ml GDF-9 reduced (P < 0.05) progesterone
      production by 15% and 600 ng/ml GDF-9 completely blocked (P < 0.01) the IGF-I
      induced increase in progesterone production. In comparison, 300 and 600 ng/ml GDF
      9 decreased (P < 0.05) estradiol production by 27% and 71% respectively, whereas
      150 ng/ml GDF-9 was without effect (P > 0.10). Treatment with 600 ng/ml GDF-9
      increased (P < 0.05) numbers (by 28%) of granulosa cells from small follicles. In
      the same cells treated with FSH but not IGF-I, co-treatment with 600 ng/ml GDF-9
      decreased (P < 0.05) progesterone production (by 28%), increased (P < 0.05) cell
      numbers (by 60%), and had no effect (P > 0.10) on estradiol production. In FSH
      plus IGF-I-treated granulosa cells obtained from large follicles, GDF-9 caused a
      dose-dependent decrease (P<0.05) in IGF-I-induced progesterone (by 13-48%) and
      estradiol (by 20-51%) production. In contrast, GDF-9 increased basal and IGF-I
      induced granulosa cell numbers by over 2-fold. Furthermore, treatment with BMP-4
      also inhibited (P < 0.05) steroidogenesis by 27-42% but had no effect on cell
      numbers. To elucidate downstream signaling pathways, granulosa cells from small
      follicles were transfected with similar to mothers against decapentaplegics
      (Smad) binding element (CAGA)- or BMP response element (BRE)-promoter reporter
      constructs. Treatment with GDF-9 (but not BMP-4) activated the Smad3-induced CAGA
      promoter activity, whereas BMP-4 (but not GDF-9) activated the Smad1/5/8-induced
      BRE promoter activity. We have concluded that bovine granulosa cells are targets
      of both GDF-9 and BMP-4, and that oocyte-derived GDF-9 may simultaneously promote
      granulosa cell proliferation and prevent premature differentiation of the
      granulosa cells during growth of follicles, whereas theca-derived BMP-4 may also
      prevent premature follicular differentiation.

PMID- 16648301
TI  - Effects of gonadotrophin in vivo and 2-hydroxyoestradiol-17beta in vitro on
      follicular steroid hormone profile associated with oocyte maturation in the
      catfish Heteropneustes fossilis.
AB  - An HPLC method was used to tentatively identify progesterone (P4) and its
      metabolites (17-hydroxyprogesterone (17-P4) and 17,20beta-dihydroxy-4-pregnen-3
      one (17,20beta-P)), corticosteroids (cortisol and corticosterone) and
      testosterone in ovary/follicular preparations of the catfish Heteropneustes
      fossilis associated with in vivo or in vitro oocyte maturation/ovulation. A
      single i.p. injection of human chorionic gonadotrophin (100 IU/fish, sampled at
      0, 8 and 16 h) induced oocyte maturation and ovulation, which coincided with
      significant and progressive increases in 17,20beta-P, and P4 and 17-P4, the
      precursors of the former. Both cortisol and corticosterone also increased
      significantly. Conversely, testosterone decreased significantly and progressively
      over time. Under in vitro conditions, incubation of post-vitellogenic (intact)
      follicles or follicular envelope (layer) with 2-hydroxyoestradiol (2-OHE2, 5
      microM for 0, 6 and 24 h) elicited a sharp significant increase in 17,20beta-P,
      the increase being higher in the follicular envelope incubate. P4 and 17-P4 also
      registered significant increases over the time with the peak values at 24 h.
      Cortisol and corticosterone increased significantly in the intact follicle, but
      not in the follicular envelope incubate. Testosterone decreased significantly in
      the intact follicle, but increased significantly (24 h) in the follicular
      envelope incubate. Coincident with these changes, the percentage of germinal
      vesicle breakdown (GVBD) increased over the time in the intact follicle incubate
      (48.9% at 6 h and 79.8% at 24 h). Denuded oocytes on incubation with 2-OHE2 (5
      microM) did not produce any significant change in the percentage of GVBD or in
      the steroid profile. While corticosterone and 17,20beta-P were undetected, P4, 17
      P4, cortisol and testosterone were detected in low amounts. The results show that
      the 2-OHE2-induced GVBD response seems to be mediated through the production of
      17,20beta-P and corticosteroids. It is suggested that hydroxyoestrogens seem to
      be a component in the gonadotrophin cascade of regulation of oocyte
      maturation/ovulation in the catfish.

PMID- 16648302
TI  - Prenatal influences on leptin sensitivity and susceptibility to diet-induced
      obesity.
AB  - Obesity and type 2 diabetes are world wide health issues and their incidence is
      rapidly increasing. Currently the biological factors responsible for the
      development of obesity are only partially understood. Recent research has shown
      that maternal nutrition during pregnancy may have long-term metabolic
      consequences in offspring. In the present study we investigated interactions
      between prenatal and postnatal nutrition on leptin sensitivity and obesity
      development. Wistar rats were time-mated and randomly assigned to either ad
      libitum (AD) or to 30% of ad-libitum (UN) food intake throughout pregnancy. After
      weaning, female offspring were fed standard chow, a high-fat diet or a calorie
      restricted diet. Female offspring of UN dams were growth retarded at birth and
      showed increased susceptibility to diet-induced obesity on a high-fat diet. At
      142 +/- 5 days of age, leptin sensitivity was measured as a response to 14 days
      of leptin treatment (2.5 microg/g/day, s.c.). In UN offspring fed chow, leptin
      treatment failed to reduce food intake and weight loss was diminished. This
      leptin resistance observed in UN offspring was independent of diet-induced
      obesity and was associated with fasting hyperinsulinemia and
      hypertriglyceridemia. Our study suggests that prenatal nutrition can shape future
      susceptibility to obesity through alterations in leptin sensitivity and changes
      in energy metabolism during adult life.

PMID- 16648303
TI  - Seabream ghrelin: cDNA cloning, genomic organization and promoter studies.
AB  - Recent studies have indicated that ghrelin stimulates growth hormone release from
      the pituitary via the growth hormone secretagogue receptor (GHSR). We have
      previously isolated two GHSR subtypes from the pituitary of the black seabream
      Acanthopagrus schlegeli. In the present study, we have cloned and characterized
      ghrelin from the same fish species at both the cDNA and gene levels. The full
      length seabream ghrelin cDNA, isolated from sea-bream stomach using a novel
      approach by exploiting a single conserved region in the coding region, was found
      to encode a prepropeptide of 107 amino acids, with the predicted mature ghrelin
      peptide consisting of 20 amino acids (GSSFLSPSQKPQNRGKSSRV). Embedded in this
      full-length cDNA is a putative fish orthologue of the recently reported mammalian
      obestatin peptide. The ghrelin gene in black seabream, obtained by genomic PCR,
      was found to encompass four exons and three introns, possessing the same
      structural organization as in tilapia and goldfish, but different from that in
      rainbow trout. In addition, a 2230-bp 5'-flanking region of the seabream ghrelin
      gene was obtained by genome walking. Sequence analysis revealed that, as in the
      case of the human ghrelin gene, there is neither a GC box nor a CAAT box present
      in the isolated 5'-flanking region. However, a number of putative transcription
      factor-binding sites different from the human counterpart were found in the 5'
      flanking region of the seabream ghrelin gene, suggesting that different cis- and
      trans-acting elements are involved in controlling their gene expression.
      Functional activity of this 5'-flanking region was examined by cloning it into
      the pGL3-Basic vector upstream of the luciferase reporter gene and transfected
      into various cell lines. Positive promoter activity could only be recorded in the
      colon-derived Caco-2 cells, suggesting that the cloned 5'-flanking region
      represents the functional promoter of the seabream ghrelin gene, which exhibits
      tissue-specific promoter activity. Using reverse transcriptase PCR analysis,
      expression of ghrelin was detected only in the seabream stomach, but not in the
      other tissues examined, including the brain, gill, intestine, kidney, liver and
      spleen. This stomach-specific expression of ghrelin in seabream is subject to
      regulation, as administration of growth hormone or ipamorelin to the fish in vivo
      was demonstrated to enhance its expression. Reminiscent of the homologous
      upregulation found in the transcriptional control of the seabream GHSR gene, a
      similar homologous regulatory mechanism might also exist in controlling the
      expression of seabream ghrelin. The identification of both GHSR and ghrelin from
      a single fish species would facilitate our subsequent studies on the elucidation
      of the physiological functions of the ghrelin/GHSR system in teleost. The
      possible existence of obestatin in teleost opens up new research avenues on the
      somatotropic axis in fish.

PMID- 16648304
TI  - FSH regulates the formation of adherens junctions and ectoplasmic specialisations
      between rat Sertoli cells in vitro and in vivo.
AB  - Spermatogenesis is dependent on the ability of Sertoli cells to form mature
      junctions that maintain a unique environment within the seminiferous epithelium.
      Adjacent Sertoli cells form a junctional complex that includes classical adherens
      junctions and testis-specific ectoplasmic specialisations (ES). The regulation of
      inter-Sertoli cell junctions by the two main endocrine regulators of
      spermatogenesis, FSH and testosterone, is unclear. This study aimed to
      investigate the effects of FSH and testosterone on inter-Sertoli cell adherens
      junctions (as determined by immunolocalisation of cadherin, catenin and actin)
      and ES junctions (as determined by immunolocalisation of espin, actin and
      vinculin) in cultured immature Sertoli cells and GnRH-immunised adult rat testes
      given FSH or testosterone replacement in vivo. When hormones were absent in
      vitro, adherens junctions formed as discrete puncta between interdigitating,
      finger-like projections of Sertoli cells, but ES junctions were not present. The
      adherens junction puncta included actin filaments that were oriented
      perpendicularly to the Sertoli cell plasma membrane, but were not associated with
      the intermediate filament protein vimentin. When FSH was added in vitro, ES
      junctions formed, and adjacent adherens junction puncta fused into extensive
      adherens junction belts. After hormone suppression in vivo, ES junctions were
      absent, while FSH replacement restored ES junctions, as confirmed by electron
      microscopy and confocal analysis of ES-associated proteins. Testosterone alone
      did not affect adherens junctions or ES in vitro or in vivo. We conclude that FSH
      can regulate the formation of ES junctions and stimulate the organisation and
      orientation of extensive adherens junctions in Sertoli cells.

PMID- 16648305
TI  - Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli
      of developing and adult rat kidney and inhibition by insulin-like peptide-3 of
      glomerular cell proliferation.
AB  - Leucine-rich repeat-containing G-protein-coupled receptor 8 (LGR8, or RXFP2) is a
      member of the type C leucine-rich repeat-containing G protein-coupled receptor
      family, and its endogenous ligand is insulin-like peptide-3 (INSL3). Although
      LGR8 expression has been demonstrated in various human tissues, including testis,
      ovary, brain and kidney, the precise roles of this receptor in many of these
      tissues are unknown. In an effort to better understand INSL3-LGR8 systems in the
      rat, we cloned the full-length Lgr8 cDNA and investigated the presence and
      cellular localization of Lgr8 mRNA expression in adult and developing rat kidney.
      On the basis of these findings, we investigated the presence and distribution of
      renal 125I-labelled human INSL3-binding sites and the nature of INSL3-LGR8
      signalling in cultured renal cells. Thus, using in situ hybridization
      histochemistry, cells expressing Lgr8 mRNA were observed in glomeruli of renal
      cortex from adult rats and were tentatively identified as mesangial cells.
      Quantitative, real-time PCR analysis of the developmental profile of Lgr8 mRNA
      expression in kidney revealed highest relative levels at late stage gestation
      (embryonic day 18), with a sharp decrease after birth and lowest levels in the
      adult. During development, silver grains associated with Lgr8 mRNA hybridization
      were observed overlying putative mesangial cells in mature glomeruli, with little
      or no signal associated with less-mature glomeruli. In adult and developing
      kidney, specific 125I-INSL3-binding sites were associated with glomeruli
      throughout the renal cortex. In primary cultures of glomerular cells, synthetic
      human INSL3 specifically and dose-dependently inhibited cell proliferation over a
      48 h period, further suggesting the presence of functional LGR8 (receptors) on
      these cells (mesangial and others). These findings suggest INSL3-LGR8 signalling
      may be involved in the genesis and/or developmental maturation of renal glomeruli
      and possibly in regulating mesangial cell density in adult rat kidney.

PMID- 16648306
TI  - Characterization of isoforms of activin receptor-interacting protein 2 that
      augment activin signaling.
AB  - Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are
      serine/threonine kinase receptors that form complexes with type I receptors to
      transmit intracellular signaling of activins, nodal, myostatin and a subset of
      bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase
      receptors in that they associate with proteins having PSD-95, Discs large and ZO
      1 (PDZ) domains. In our previous studies, we reported specific interactions of
      ActRIIs with two independent PDZ proteins named activin receptor-interacting
      proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce
      activin-induced transcription. Here, we report the isolation of two isoforms of
      ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal
      residues of ActRIIA that match a PDZ-binding consensus motif. ARIP2 and its
      isoforms have one PDZ domain in the NH2-terminal region, and interact with
      ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are
      identical to that of ARIP2, their COOH-terminal sequences differ from that of
      ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect
      ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin
      signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/2c is expressed
      in more restricted tissues such as heart, brain, kidneys and liver. Our results
      indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors,
      they regulate ActRIIA function in a different manner.

PMID- 16648307
TI  - Changes in the psychiatric landscape.

PMID- 16648308
TI  - Polishing the windows of the mind.

PMID- 16648309
TI  - What's in a word? Addiction versus dependence in DSM-V.

PMID- 16648310
TI  - Philanthropy for psychiatry.

PMID- 16648311
TI  - Can early detection of psychosis prevent suicidal behavior?

PMID- 16648313
TI  - Discovering light effects on the brain.

PMID- 16648314
TI  - Ethical philanthropy in academic psychiatry.
AB  - OBJECTIVE: From an ethical perspective, psychiatrists cannot accept gifts of
      significant monetary value from their patients. This guideline raises important
      questions regarding institutional practices related to gift-giving in academic
      psychiatry. The first aim of this article is to explain the ethical tensions and
      shared ethical commitments of the professions of psychiatry and philanthropy. The
      second aim is to outline a series of steps that may be undertaken to assure
      ethical philanthropic practices within an institution, including the
      establishment of a committed advisory workgroup and the creation of ground rules
      and safeguards for gift-giving. Each situation should be evaluated for "ethical
      risk," and specific measures to safeguard donors should be considered. METHOD:
      The author outlines methods to manage, minimize, or eliminate conflict of
      interest issues, including identification and disclosure of conflicting
      interests, role separation, goal clarification, confidentiality protections,
      proper timing, and ongoing oversight. Three case illustrations are provided and
      discussed. RESULTS: The process of institutional engagement, dialogue, and shared
      problem-solving is especially important. A shared, constructive ethic will be
      attained only if leaders and diverse stakeholders communicate the value of the
      new approach through their words, expectations, and actions. CONCLUSIONS: Through
      these efforts, greater attention will be given to the concerns of people with
      mental illness, and academic institutions may be better able to fulfill their
      responsibilities to this important but neglected population now and in the
      future.

PMID- 16648315
TI  - Hallucinations in children and adolescents: considerations in the emergency
      setting.

PMID- 16648316
TI  - Anhedonia after a selective bilateral lesion of the globus pallidus.

PMID- 16648318
TI  - Randomized, double-blind trial of olanzapine versus placebo in patients
      prodromally symptomatic for psychosis.
AB  - OBJECTIVE: This study assessed the efficacy of olanzapine in delaying or
      preventing conversion to psychosis and reducing symptoms in people with prodromal
      symptoms of schizophrenia. METHOD: This randomized trial occurred at four North
      American clinics in the Prevention Through Risk Identification, Management, and
      Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo
      (N=29) during a 1-year double-blind treatment period and no treatment during a 1
      year follow-up period. Efficacy measures included the conversion-to-psychosis
      rate and Scale of Prodromal Symptoms scores. RESULTS: During the treatment year,
      16.1% of olanzapine patients and 37.9% of placebo patients experienced a
      conversion to psychosis, a nearly significant difference. The hazard of
      conversion among placebo patients was about 2.5 times that among olanzapine
      treated patients, which also approached significance. In the follow-up year, the
      conversion rate did not differ significantly between groups. During treatment,
      the mean score for prodromal positive symptoms improved more in the olanzapine
      group than in the placebo group, and the mixed-model repeated-measures least
      squares mean score showed significantly greater improvement between weeks 8 and
      28 with olanzapine. The olanzapine patients gained significantly more weight
      (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24). CONCLUSIONS: A significant
      treatment difference in the conversion-to-psychosis rate was not demonstrated.
      However, these results may be influenced by low power. The nearly significant
      differences suggest that olanzapine might reduce the conversion rate and delay
      onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms
      but induced weight gain. Further treatment research in this phase of illness is
      warranted.

PMID- 16648319
TI  - Early detection of the first episode of schizophrenia and suicidal behavior.
AB  - OBJECTIVE: The suicide rate in schizophrenia is high, with the risk being highest
      early in the course. The rate of suicide attempts before treatment onset is also
      high and is often the event leading up to first treatment contact. A previous
      report showed that the duration of untreated psychosis can be reduced through an
      early detection program, and that the reduction was associated with lower symptom
      levels at treatment initiation. Treatment programs that bring first-episode
      patients into treatment at lower symptom levels can have the potential to reduce
      risk for suicide attempts. METHOD: The authors examined consecutive patients with
      nonorganic, nonaffective psychosis who sought initial treatment at psychiatric
      treatment units in four catchment areas: two that had an early detection program
      and two that did not. RESULTS: The rate of severe suicidality (plans or attempts)
      was significantly higher in subjects from communities without the early detection
      program relative to those from early detection communities, even after
      adjustments for known predictors of suicidality. CONCLUSION: Early detection
      programs that bring patients into treatment at lower symptom levels may reduce
      suicidality risk at first treatment contact.

PMID- 16648320
TI  - The Can-SAD study: a randomized controlled trial of the effectiveness of light
      therapy and fluoxetine in patients with winter seasonal affective disorder.
AB  - OBJECTIVE: Light therapy and antidepressants have shown comparable efficacy in
      separate studies of seasonal affective disorder treatment, but few studies have
      directly compared the two treatments. This study compared the effectiveness of
      light therapy and an antidepressant within a single trial. METHOD: This double
      blind, randomized, controlled trial was conducted in four Canadian centers over
      three winter seasons. Patients met DSM-IV criteria for major depressive disorder
      with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton
      Depression Rating Scale. After a baseline observation week, eligible patients
      were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000
      lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo
      light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day
      in the morning with a fluorescent white-light box; placebo light boxes used
      neutral density filters. RESULTS: A total of 96 patients were randomly assigned
      to a treatment condition. Intent-to-treat analysis showed overall improvement
      with time, with no differences between treatments. There were also no differences
      between the light and fluoxetine treatment groups in clinical response rates (67%
      for each group) or remission rates (50% and 54%, respectively). Post hoc testing
      found that light-treated patients had greater improvement at 1 week but not at
      other time points. Fluoxetine was associated with greater treatment-emergent
      adverse events (agitation, sleep disturbance, palpitations), but both treatments
      were generally well-tolerated with no differences in overall number of adverse
      effects. CONCLUSIONS: Light treatment showed earlier response onset and lower
      rate of some adverse events relative to fluoxetine, but there were no other
      significant differences in outcome between light therapy and antidepressant
      medication. Although limited by lack of a double-placebo condition, this study
      supports the effectiveness and tolerability of both treatments for seasonal
      affective disorder and suggests that other clinical factors, including patient
      preference, should guide selection of first-line treatment.

PMID- 16648321
TI  - The risk of suicide with selective serotonin reuptake inhibitors in the elderly.
AB  - OBJECTIVE: The authors explored the relationship between the initiation of
      therapy with selective serotonin reuptake inhibitor (SSRI) antidepressants and
      completed suicide in older patients. METHOD: The authors linked population-based
      coroner's records with patient-level prescription data, physician billing claims,
      and hospitalization data for more than 1.2 million Ontario residents 66 years of
      age and older from 1992 to 2000. For each suicide case, four closely matched
      comparison subjects were selected using propensity score methods. The authors
      determined the odds ratio for suicide with SSRIs versus other antidepressant
      treatment, calculated at discrete monthly intervals from the start of treatment.
      RESULTS: Of 1,329 suicide cases, 1,138 (86%) were each fully matched to four
      comparison subjects using propensity scores. During the first month of therapy,
      SSRI antidepressants were associated with a nearly fivefold higher risk of
      completed suicide than other antidepressants (adjusted odds ratio: 4.8, 95%
      confidence interval=1.9-12.2). The risk was independent of a recent diagnosis of
      depression or the receipt of psychiatric care, and suicides of a violent nature
      were distinctly more common during SSRI therapy. Numerous sensitivity analyses
      revealed consistent results. No disproportionate suicide risk was seen during the
      second and subsequent months of treatment with SSRI antidepressants, and the
      absolute risk of suicide with all antidepressants was low. CONCLUSIONS:
      Initiation of SSRI therapy is associated with an increased risk of suicide during
      the first month of therapy compared with other antidepressants. The absolute risk
      is low, suggesting that an idiosyncratic response to these agents may provoke
      suicide in a vulnerable subgroup of patients.

PMID- 16648322
TI  - Predictors of 2-year outcome for patients with borderline personality disorder.
AB  - OBJECTIVE: The primary purpose of this report was to investigate whether
      characteristics of subjects with borderline personality disorder observed at
      baseline can predict variations in outcome at the 2-year follow-up. METHOD:
      Hypothesized predictor variables were selected from prior studies. The patients
      (N=160) were recruited from the four clinical sites of the Collaborative
      Longitudinal Personality Disorders Study. Patients were assessed at baseline and
      at 6, 12, and 24 months with the Structured Clinical Interview for DSM-IV Axis I
      Disorders; the Diagnostic Interview for DSM-IV Personality Disorders, a modified
      version of that instrument; the Longitudinal Interval Follow-Up Evaluation; and
      the Childhood Experiences Questionnaire-Revised. Univariate Pearson's correlation
      coefficients were calculated on the primary predictor variables, and with two
      forward stepwise regression models, outcome was assessed with global functioning
      and number of borderline personality disorder criteria. RESULTS: The authors'
      most significant results confirm prior findings that more severe baseline
      psychopathology (i.e., higher levels of borderline personality disorder criteria
      and functional disability) and a history of childhood trauma predict a poor
      outcome. A new finding suggests that the quality of current relationships of
      patients with borderline personality disorder have prognostic significance.
      CONCLUSIONS: Clinicians can estimate 2-year prognosis for patients with
      borderline personality disorder by evaluating level of severity of
      psychopathology, childhood trauma, and current relationships.

PMID- 16648323
TI  - Prediction of the 10-year course of borderline personality disorder.
AB  - OBJECTIVE: The purpose of this study was to determine the most clinically
      relevant baseline predictors of time to remission for patients with borderline
      personality disorder. METHOD: A total of 290 inpatients meeting criteria for both
      the Revised Diagnostic Interview for Borderlines and DSM-III-R for borderline
      personality disorder were assessed during their index admission with a series of
      semistructured interviews and self-report measures. Diagnostic status was
      reassessed at five contiguous 2-year time periods. Discrete survival analytic
      methods, which controlled for baseline severity of borderline psychopathology and
      time, were used to estimate hazard ratios. RESULTS: Eighty-eight percent of the
      patients with borderline personality disorder studied achieved remission. In
      terms of time to remission, 39.3% of the 242 patients who experienced a remission
      of their disorder first remitted by their 2-year follow-up, an additional 22.3%
      first remitted by their 4-year follow-up, an additional 21.9% by their 6-year
      follow-up, an additional 12.8% by their 8-year follow-up, and another 3.7% by
      their 10-year follow-up. Sixteen variables were found to be significant bivariate
      predictors of earlier time to remission. Seven of these remained significant in
      multivariate analyses: younger age, absence of childhood sexual abuse, no family
      history of substance use disorder, good vocational record, absence of an anxious
      cluster personality disorder, low neuroticism, and high agreeableness.
      CONCLUSIONS: The results of this study suggest that prediction of time to
      remission from borderline personality disorder is multifactorial in nature,
      involving factors that are routinely assessed in clinical practice and factors,
      particularly aspects of temperament, that are not.

PMID- 16648324
TI  - Aripiprazole in the treatment of patients with borderline personality disorder: a
      double-blind, placebo-controlled study.
AB  - OBJECTIVE: Aripiprazole is a relatively new atypical antipsychotic agent that has
      been successfully employed in therapy for schizophrenia and schizoaffective
      disorders. A few neuroleptics have been used in therapy for patients with
      borderline personality disorder, which is associated with severe
      psychopathological symptoms. Aripiprazole, however, has not yet been tested for
      this disorder, and the goal of this study was to determine whether aripiprazole
      is effective in the treatment of several domains of symptoms of borderline
      personality disorder. METHOD: Subjects meeting criteria for the Structured
      Clinical Interview for DSM-III-R Personality Disorders for borderline personality
      disorder (43 women and 9 men) were randomly assigned in a 1:1 ratio to 15 mg/day
      of aripiprazole (N=26) or placebo (N=26) for 8 weeks. Primary outcome measures
      were changes in scores on the symptom checklist (SCL-90-R), the Hamilton
      Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and
      the State-Trait Anger Expression Inventory and were assessed weekly. Side effects
      and self-injury were assessed with a nonvalidated questionnaire. RESULTS:
      According to the intent-to-treat principle, significant changes in scores on most
      scales of the SCL-90-R, the HAM-D, the HAM-A, and all scales of the State-Trait
      Anger Expression Inventory were observed in the subjects treated with
      aripiprazole after 8 weeks. Self-injury occurred in the groups. The reported side
      effects were headache, insomnia, nausea, numbness, constipation, and anxiety.
      CONCLUSIONS: Aripiprazole appears to be a safe and effective agent in the
      treatment of patients with borderline personality disorder.

PMID- 16648325
TI  - Neuroticism and affective instability: the same or different?
AB  - OBJECTIVE: The purpose of this study was to examine the correlates and
      consequences of two constructs related to affective experience: neuroticism and
      affective instability. METHOD: One hundred thirty-two patients were assessed at
      intake for axis I and II symptoms, general personality traits, and specific
      impairments, including impairments in interpersonal functioning. The data
      included responses to structured and semistructured interviews, self-reports of
      interpersonal problems, and reports of interpersonal problems from significant
      others. Clinical ratings of axis I and II symptoms and of impairment were made by
      using the LEAD (i.e., longitudinal, expert, all data) consensus approach. Ninety
      one of the 132 patients were reassessed at 12-month follow-up. RESULTS:
      Neuroticism and affective instability manifested varied concurrent relations,
      with neuroticism being strongly related to an anxious, avoidant style and
      affective instability related to more externalizing personality styles.
      Prospectively, neuroticism predicted later symptoms, occupational impairment, and
      global dysfunction, whereas affective instability predicted romantic impairment.
      CONCLUSIONS: The findings suggest that neuroticism and affective instability-
      which are considered core aspects of personality pathology--are related but
      distinct constructs with unique correlates and different predictive abilities.

PMID- 16648326
TI  - A prototype approach to personality disorder diagnosis.
AB  - OBJECTIVE: Virtually no research has tested alternatives to the diagnostic method
      used since DSM-III, which requires decisions about the presence/absence of
      individual diagnostic criteria, followed by counting symptoms and applying
      cutoffs (the count/cutoff method). This study tested an alternative, prototype
      matching procedure designed to simplify diagnosis. The procedure was applied to
      personality disorders. METHOD: A random national sample of psychiatrists and
      clinical psychologists (N=291) described a randomly selected patient in their
      care. Clinician-provided diagnostic data were used to generate categorical and
      dimensional DSM-IV diagnoses (number of symptoms present per disorder).
      Clinicians also used one of two prototype matching systems to provide a diagnosis
      for the selected patient. RESULTS: Prototype diagnosis led to reduced comorbidity
      relative to DSM-IV diagnosis, yielded similar estimates of validity in predicting
      criterion variables (adaptive functioning, treatment response, and etiology), and
      outperformed DSM-IV diagnosis in ratings of clinical utility and ease of use.
      Adding a personality health prototype further increased prediction. CONCLUSIONS:
      A simple prototype matching procedure provides a viable alternative for improving
      diagnosis of personality disorders in clinical practice. Prototype diagnosis has
      multiple advantages, including ease of use, minimization of artifactual
      comorbidity, compatibility with naturally occurring cognitive processes, and
      ready translation into both categorical and dimensional diagnosis.

PMID- 16648327
TI  - A population-based twin study of the relationship between neuroticism and
      internalizing disorders.
AB  - OBJECTIVE: The anxiety and depressive disorders exhibit high levels of lifetime
      comorbidity with one another. The authors examined how genetic and environmental
      factors shared by the personality trait neuroticism and seven internalizing
      disorders may help explain this comorbidity. METHOD: Lifetime major depression,
      generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal
      phobia, situational phobia, and neuroticism were assessed in over 9,000 twins
      from male-male, female-female, and opposite-sex pairs through structured
      diagnostic interviews. Multivariate structural equation models were used to
      decompose the correlations between these phenotypes into genetic and
      environmental components, allowing for sex-specific factors. RESULTS: Genetic
      factors shared with neuroticism accounted for between one-third and one-half of
      the genetic risk across the internalizing disorders. When nonsignificant gender
      differences were removed from the models, the genetic correlations between
      neuroticism and each disorder were high, while individual-specific environmental
      correlations were substantially lower. In addition, the authors could identify a
      neuroticism-independent genetic factor that significantly increased risk for
      major depression, generalized anxiety disorder, and panic disorder. CONCLUSIONS:
      There is substantial, but not complete, overlap between the genetic factors that
      influence individual variation in neuroticism and those that increase liability
      across the internalizing disorders, helping to explain the high rates of
      comorbidity among the latter. This may have important implications for
      identifying the susceptibility genes for these conditions.

PMID- 16648328
TI  - Ten-year stability of depressive personality disorder in depressed outpatients.
AB  - OBJECTIVE: The purpose of this study was to examine the long-term stability of
      depressive personality disorder. METHOD: The subjects included 142 outpatients
      with axis I depressive disorders at study entry; 73 had depressive personality
      disorder. The patients were assessed by using semistructured diagnostic
      interviews at baseline and in four follow-up evaluations at 2.5-year intervals
      over 10.0 years. Follow-up data were available for 127 (89.4%) of the patients.
      RESULTS: The 10.0-year stability of the diagnoses of depressive personality
      disorder was fair, and the rate of depressive personality disorder declined over
      time. The dimensional score was moderately stable over 10.0 years. Growth curve
      analyses revealed a sharp decline in the level of depressive personality disorder
      traits between the baseline and 2.5-year assessments, followed by a gradual
      linear decrease. Reductions in depressive personality disorder traits were
      associated with remission of the axis I depressive disorders. Finally, depressive
      personality disorder at baseline predicted the trajectory of depressive symptoms
      over time in patients with dysthymic disorder. CONCLUSIONS: Depressive
      personality disorder is moderately stable, particularly when assessed with a
      dimensional approach. However, the diagnosis rate and traits of depressive
      personality disorder tend to decline over time. The degree of stability for
      depressive personality disorder is comparable to that for the axis II disorders
      in the main text of DSM-IV. Finally, depressive personality disorder has
      prognostic implications for the course of axis I mood disorders, such as
      dysthymic disorder.

PMID- 16648329
TI  - Ten-year prospective follow-up study of the naturalistic course of dysthymic
      disorder and double depression.
AB  - OBJECTIVE: The purpose of this study was to describe the 10-year course and
      outcome of dysthymic disorder. METHOD: The authors conducted a naturalistic,
      prospective, longitudinal follow-up of 97 adults with early-onset dysthymic
      disorder and 45 adults with nonchronic major depressive disorder selected from
      consecutive admissions to several outpatient facilities. Follow-up data were
      obtained for 90% of the cohort. Assessments were conducted at baseline, 30, 60,
      90, and 120 months. Measures included the Longitudinal Interval Follow-Up
      Evaluation and the Hamilton Depression Rating Scale. RESULTS: The Kaplan-Meier
      estimated recovery rate from dysthymic disorder was 73.9%, with a median time to
      recovery of 52 months. Among patients who recovered, the estimated risk of
      relapse into another period of chronic depression was 71.4%. Chronic depressive
      relapses took a variety of forms and were not limited to dysthymia. Nonetheless,
      the distinction between chronic and nonchronic forms of depression was relatively
      stable over the follow-up period. Mixed-effects models indicated that patients
      with dysthymic disorder experienced a significantly slower rate of improvement in
      symptoms over time and exhibited significantly greater depression at the 10-year
      point, compared to patients with nonchronic major depression. CONCLUSIONS:
      Dysthymic disorder has a protracted course and is associated with a high risk of
      relapse. The nature of chronic depressive episodes varies over time within
      individuals, indicating that the various manifestations of chronic depression in
      DSM-IV do not represent distinct disorders. However, the distinction between
      chronic and nonchronic forms of depression is relatively stable and may provide a
      useful basis for subtyping in genetic and neurobiological research.

PMID- 16648330
TI  - Symptoms of posttraumatic stress disorder in a community sample of low-income
      pregnant women.
AB  - OBJECTIVE: The purpose of this study was to examine symptoms of posttraumatic
      stress disorder (PTSD) in a community sample of low-income pregnant women who met
      the DSM-IV diagnostic criteria for the disorder. METHOD: Pregnant women (N=948)
      were screened for trauma, PTSD, depression, and co-occurring illicit substance
      use. PTSD symptoms were compared in traumatized pregnant women and a sample of
      nonpregnant traumatized women from the National Comorbidity Survey. RESULTS:
      Suicidal thoughts and a high degree of psychiatric comorbidity were common in
      pregnant women with PTSD. Pregnant women were selectively and significantly less
      likely to endorse reexperiencing symptoms of PTSD (29.5%, N=82), compared to
      nonpregnant women (79.4%, N=464). CONCLUSIONS: PTSD in pregnancy was associated
      with comorbidity, poor health behaviors, and lower recall of memory-related PTSD
      symptoms. Further prospective study is needed.

PMID- 16648331
TI  - Is domestic violence followed by an increased risk of psychiatric disorders among
      women but not among men? A longitudinal cohort study.
AB  - OBJECTIVE: The association between violence between intimate partners and
      psychiatric disorders is assumed to reflect a causal link. This assumption is now
      questioned because several longitudinal studies have documented that adolescents
      with psychiatric disorders grow up to be overrepresented among adults involved in
      partner violence. METHOD: The study followed a representative birth cohort
      prospectively. Adolescent mental disorders were diagnosed at age 18 years.
      Between ages 24 and 26 years, the authors identified individuals involved in
      nonabusive relationships versus those involved in clinically abusive
      relationships (i.e., resulting in injury and/or official intervention). At age 26
      years, mental disorders were again diagnosed. RESULTS: Male and female
      adolescents with psychiatric disorders were at greatest risk of becoming involved
      in abusive adult relationships. After the authors controlled for earlier
      psychiatric history, women who were involved in abusive relationships, but not
      men, had an increased risk of adult psychiatric morbidity. CONCLUSIONS: 1)
      Psychiatric disorders pose risk for involvement in abusive relationships for both
      sexes; 2) partner abuse is a contributing source of psychiatric disorders among
      women but not among men.

PMID- 16648332
TI  - A randomized, placebo-controlled trial of sertraline in the treatment of night
      eating syndrome.
AB  - OBJECTIVE: The authors assessed the efficacy of sertraline in the treatment of
      night eating syndrome. METHOD: Thirty-four outpatients diagnosed with night
      eating syndrome were randomly assigned to receive either sertraline (N=17) or
      placebo (N=17) in an 8-week, double-blind, flexible-dose (50-200 mg/day) study. A
      mixed effects linear regression model was used to analyze change in the primary
      outcome measure, Clinical Global Impression (CGI) improvement rating. Secondary
      outcomes included changes in night eating symptoms, the number of nocturnal
      awakenings and ingestions, total daily caloric intake after the evening meal, CGI
      severity ratings, quality of life ratings, and weight. RESULTS: Sertraline was
      associated with significantly greater improvement than placebo. Twelve subjects
      in the sertraline group (71%) were classified as having responded (CGI
      improvement rating < or = 2, indicating much or very much improved) versus only
      three (18%) in the placebo group. There were also significant improvements in
      night eating symptoms, CGI severity ratings, quality of life ratings, frequency
      of nocturnal ingestions and awakenings, and caloric intake after the evening
      meal. Overweight and obese subjects in the sertraline group (N=14) lost a
      significant amount of weight by week 8 (mean=-2.9 kg, SD=3.8) compared with
      overweight and obese subjects receiving placebo (N=14) (mean=-0.3 kg, SD=2.7).
      CONCLUSIONS: In this 8-week trial, sertraline was effective in the treatment of
      night eating syndrome and was well tolerated.

PMID- 16648333
TI  - Treating disturbances in the relationship between mothers with bulimic eating
      disorders and their infants: a randomized, controlled trial of video feedback.
AB  - OBJECTIVE: Maternal eating disorders interfere with parenting, adversely
      affecting mother-infant interaction and infant outcome. This trial tested whether
      video-feedback treatment specifically targeting mother-child interaction would be
      superior to counseling in improving mother-child interaction, especially mealtime
      conflict, and infant weight and autonomy. METHOD: The participants were 80
      mothers with bulimia nervosa or similar eating disorder who were attending
      routine baby clinics and whose infants were 4-6 months old. They were randomly
      assigned to video-feedback interactional treatment or supportive counseling. Both
      groups also received guided cognitive behavior self-help for their eating
      disorder. Each group received 13 sessions. The primary outcome measure was
      mealtime conflict; secondary outcome measures were infant weight, aspects of
      mother-infant interaction, and infant autonomy. RESULTS: Seventy-seven mothers
      were followed up when their infants were 13 months old. The video-feedback group
      exhibited significantly less mealtime conflict than the control subjects. Nine of
      38 (23.7%) in the video-feedback group showed episodes of marked or severe
      conflict, compared with 21 of 39 (53.8%) control subjects (odds ratio=0.27, 95%
      confidence interval=0.10 to 0.73). Video feedback produced significant
      improvements in several other interaction measures and greater infant autonomy.
      Both groups maintained good infant weight, with no differences between groups.
      Maternal eating psychopathology was reduced across both groups. CONCLUSIONS:
      Video-feedback treatment focusing on mother-infant interaction produced
      improvements in interaction and infant autonomy, and both groups maintained
      adequate infant weight. To the authors' knowledge, this is the first controlled
      trial to show key improvements in interaction between mothers with postnatal
      psychiatric disorders and their infants.

PMID- 16648334
TI  - A 12-month follow-up study of the course of body dysmorphic disorder.
AB  - OBJECTIVE: This study investigated the course of body dysmorphic disorder (BDD),
      a relatively common and severe disorder, in the first prospective follow-up
      study, to the authors' knowledge. METHOD: In this study, the authors obtained
      data with the Longitudinal Interval Follow-Up Evaluation on weekly BDD symptom
      status and treatment received over 1 year for 183 broadly ascertained subjects.
      Probabilities of full remission, partial remission, and relapse during this year
      were examined. Full remission was defined as minimal or no BDD symptoms and
      partial remission, as meeting less than full DSM-IV criteria for at least 8
      consecutive weeks. Relapse was defined as meeting full BDD criteria for at least
      2 consecutive weeks after attaining partial or full remission from BDD. RESULTS:
      Over 1 year, the probability of full remission from BDD was only 0.09, and the
      probability of partial remission was 0.21. Although 84.2% of the subjects
      received mental health treatment during the 1-year period, mean BDD severity
      scores during the year reflected full DSM-IV criteria for BDD, and the mean
      proportion of time that the subjects met full BDD criteria was 80%. Gender and
      ethnicity did not significantly predict remission from BDD. Among the subjects
      whose BDD symptoms partially or fully remitted, the probability of relapse was
      0.15. CONCLUSIONS: These findings indicate that BDD tends to be chronic.
      Remission probabilities were lower than reported for mood disorders, most anxiety
      disorders, and personality disorders in studies with similar methods.

PMID- 16648335
TI  - The persistence of mind-brain dualism in psychiatric reasoning about clinical
      scenarios.
AB  - OBJECTIVE: Despite attempts in psychiatry to adopt an integrative biopsychosocial
      model, social scientists have observed that psychiatrists continue to operate
      according to a mind-brain dichotomy in ways that are often covert and
      unacknowledged and suggest that the same intuitive cognitive schemas that people
      use to make judgments of responsibility lead to dualistic reasoning among
      clinicians. The goal of this study was to confirm these observations. METHOD:
      Self-report questionnaires were sent to the 270 psychiatrists and psychologists
      in the Department of Psychiatry at McGill University. In response to clinical
      vignettes, the participants rated the level of intentionality, controllability,
      responsibility, and blame attributable to the patients, as well as the importance
      of neurobiological, psychological, and social factors in explaining the patients'
      symptoms. RESULTS: A total of 136 faculty members (50.4%) responded, and 127 were
      included in the analysis. Factor analysis revealed a single dimension of
      responsibility regarding the patients' illnesses that correlated positively with
      ratings of psychological etiology and negatively with ratings of neurobiological
      etiology. Psychological and neurobiological ratings were inversely correlated.
      Multivariate analyses of variance supported these results. CONCLUSIONS: Mental
      health professionals continue to employ a mind-brain dichotomy when reasoning
      about clinical cases. The more a behavioral problem is seen as originating in
      "psychological" processes, the more a patient tends to be viewed as responsible
      and blameworthy for his or her symptoms; conversely, the more behaviors are
      attributed to neurobiological causes, the less likely patients are to be viewed
      as responsible and blameworthy.

PMID- 16648336
TI  - Neuroscience in psychiatry training: how much do residents need to know?
AB  - OBJECTIVE: With the explosion of research in psychiatric neuroscience, the extent
      and means by which neuroscientific progress will translate into clinical care
      remains largely uncertain. The authors sought to determine how this dilemma is
      currently being played out in residency training programs, in which training
      directors must decide how best to integrate neuroscience teaching in a rapidly
      changing clinical landscape. METHOD: The authors surveyed U.S. and Canadian
      psychiatry residency training directors to characterize current and future trends
      in neuroscience education and to examine training directors' views on the
      relevance of neuroscience to clinical practice. RESULTS: The amount of
      neuroscience in residency curricula has increased significantly over the past 5
      years, and further increases are expected in each specific neuroscience content
      area examined. While most training directors agreed that training in neuroscience
      was important for all residents, even those becoming primarily psychotherapists,
      relevance to future (but not current) practice was consistently cited as a
      motivating factor. CONCLUSIONS: While psychiatric residency programs continue to
      increase the neuroscience content of their curricula, it remains unclear how this
      added training will influence clinical work. Reframing current practices,
      including psychotherapy, into a neuroscientific context may ultimately prove more
      useful to trainees.

PMID- 16648337
TI  - Prenatal exposure to maternal genital and reproductive infections and adult
      schizophrenia.
AB  - OBJECTIVE: In this birth cohort study, the authors examined the relation between
      prenatal exposure to maternal genital/reproductive (G/R) infections and
      schizophrenia in offspring. METHOD: The birth cohort consisted of 7,794 offspring
      of pregnancies with prospectively acquired data on maternal G/R infections from
      obstetric records. The authors diagnosed 71 cases of schizophrenia and other
      schizophrenia spectrum disorders in this cohort. The relationship between
      maternal G/R infections and schizophrenia risk was modeled. RESULTS: Exposure to
      G/R infections during the periconceptional period was associated with a
      significantly increased risk of schizophrenia and other schizophrenia spectrum
      disorders, with adjustment for maternal race, education, age, and mental illness.
      CONCLUSIONS: Maternal G/R infection during periconception appears to increase the
      risk of schizophrenia in offspring.

PMID- 16648338
TI  - Lack of association between autism and SLC25A12.
AB  - OBJECTIVE: Autism has a strong, complex genetic component, most likely involving
      several genes. Multiple genomic screens have shown evidence suggesting linkage to
      chromosome 2q31-q33, which includes the SLC25A12 gene. Recently, an association
      between autism risk and two single nucleotide polymorphisms (SNPs) in SLC25A12
      was reported. This study aimed to test for association in SLC25A12 in an
      independent data set of 327 families with autistic offspring. METHOD: The authors
      analyzed two SNPs that were significant in the previous study group, as well as
      seven additional SNPs within the gene. Association analyses for individual SNPs
      as well as haplotypes were performed. RESULTS: There was no evidence of an
      association between SLC25A12 and autism. CONCLUSIONS: These results suggest that
      SLC25A12 is not a major contributor to autism risk in these families.

PMID- 16648339
TI  - Olfactory identification deficits in first-episode psychosis may predict patients
      at risk for persistent negative and disorganized or cognitive symptoms.
AB  - OBJECTIVE: One-third of patients with a schizophrenia spectrum disorder have a
      measurable olfactory identification deficit at first examination. The authors
      studied the relationship of this deficit to symptom remission after 1 year of
      treatment. METHOD: Fifty-eight patients naive to antipsychotic medication who
      entered the Nova Scotia Early Psychosis Program were symptomatically rated with
      the Positive and Negative Syndrome Scale (PANSS) (at baseline and 1 year). At
      baseline, the University of Pennsylvania Smell Identification Test (UPSIT) was
      also completed. Remission was determined for four symptom factors derived from
      the PANSS (positive, negative, cognitive/disorganized, and anxiety/depression).
      Patients with and without remission were compared on UPSIT scores. RESULTS:
      Patients with nonremission of negative and cognitive/disorganized symptoms had
      significantly lower baseline UPSIT scores compared with patients with remission.
      UPSIT scores were unrelated to remission of positive or anxiety/depression
      symptoms. CONCLUSIONS: UPSIT scores can be used to identify patients at risk for
      persistent negative and disorganized/cognitive symptoms.

PMID- 16648340
TI  - Cortical serotonin 5-HT2A receptor binding and social communication in adults
      with Asperger's syndrome: an in vivo SPECT study.
AB  - OBJECTIVE: The cause of autistic spectrum disorder (i.e., autism and Asperger's
      syndrome) is unknown. The serotonergic (5-HT) system may be especially
      implicated. However, cortical 5-HT2A receptor density in adults with the disorder
      has not been examined, to the authors' knowledge. METHOD: The authors
      investigated cortical 5-HT2A receptor binding in eight adults with Asperger's
      syndrome and in 10 healthy comparison subjects with single photon emission
      computed tomography and the selective 5-HT2A receptor ligand 123I iodinated 4
      amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2
      methoxybenzamide (123I-5-I-R91150). RESULTS: People with Asperger's syndrome had
      a significant reduction in cortical 5-HT2A receptor binding in the total,
      anterior, and posterior cingulate; bilaterally in the frontal and superior
      temporal lobes; and in the left parietal lobe. Also, reduced receptor binding was
      significantly related to abnormal social communication. CONCLUSIONS: The authors'
      findings suggest that adults with Asperger's syndrome have abnormalities in
      cortical 5-HT2A receptor density and that this deficit may underlie some clinical
      symptoms.

PMID- 16648341
TI  - Group therapy with schizophrenia patients.

PMID- 16648342
TI  - Do schizophrenia patients want to be involved in their treatment?

PMID- 16648343
TI  - New-onset tardive dyskinesia in patients with first-episode psychosis receiving
      risperidone or haloperidol.

PMID- 16648344
TI  - Depressive symptoms as first manifestation of posterior cortical atrophy.

PMID- 16648345
TI  - Are high-risk haplotypes in DTNBP1 and NRG1 resistance genes for schizophrenia?

PMID- 16648346
TI  - Integration of mental health care and supported employment.

PMID- 16648348
TI  - Coughs and wheezes spread diseases: but what about the environment?

PMID- 16648349
TI  - Risk management of the home ventilator dependent patient.

PMID- 16648350
TI  - Collateral ventilation.

PMID- 16648351
TI  - Got a match? Home oxygen therapy in current smokers.

PMID- 16648352
TI  - COPD exacerbations. 4: Prevention.

PMID- 16648354
TI  - Acute respiratory distress syndrome due to pulmonary involvement by neoplastic
      plasma cells in multiple myeloma.
AB  - Pulmonary involvement with multiple myeloma occurs infrequently and may be
      difficult to distinguish from more common primary lung tumours, metastatic
      disease, or other pleural and parenchymal abnormalities. A patient who developed
      acute respiratory distress syndrome (ARDS) was subsequently found to have
      multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells.
      Only one other report of ARDS in association with multiple myeloma was found, and
      there are no previous reports where the appearance of ARDS antedated a diagnosis
      of multiple myeloma. In patients with ARDS, parenchymal involvement from multiple
      myeloma should be included in the differential diagnosis.

PMID- 16648353
TI  - Inflammatory cells in the airways in COPD.
AB  - Airway inflammation is central to the pathogenesis of both airway remodelling and
      parenchymal destruction in chronic obstructive pulmonary disease (COPD).
      Neutrophils, macrophages, and CD8+ T lymphocytes have been implicated in a number
      of studies, but a detailed profile of disease-phenotype specific inflammation has
      yet to emerge. The heterogeneity of the disease has hindered data interpretation
      while extrapolation of the results of relatively non-invasive studies to the
      actual pathology found in the distal lung is difficult. Moreover, prominent
      studies have had frequently conflicting results. Further investigations are
      needed to marry the different clinical phenotypes of COPD to their respective
      inflammatory profiles in the airways and thus improve our understanding of the
      pathogenesis of the disease as a whole.

PMID- 16648355
TI  - Compliance and reliability of electronic PEF monitoring in adolescents with
      asthma.

PMID- 16648356
TI  - Bronchiectasis and non-tuberculous mycobacterial pulmonary infection.

PMID- 16648357
TI  - The Drosophila termination factor DmTTF regulates in vivo mitochondrial
      transcription.
AB  - DmTTF is a Drosophila mitochondrial DNA-binding protein, which recognizes two
      sequences placed at the boundary of clusters of genes transcribed in opposite
      directions. To obtain in vivo evidences on the role of DmTTF, we characterized a
      DmTTF knock-down phenotype obtained by means of RNA interference in D.Mel-2
      cells. By a combination of RNase protection and real-time RT-PCR experiments we
      found that knock-down determines remarkable changes in mitochondrial
      transcription. In particular, protein depletion increases not only the level of
      (+) and (-)strand RNAs mapping immediately after of the two protein-binding site,
      but also that of transcripts located further downstream. Unexpectedly, depletion
      of the protein also causes the decrease in the content of those transcripts
      mapping upstream of the protein target sites, including the two rRNAs. The
      changes in transcript level do not depend on a variation in mitochondrial DNA
      (mtDNA) content, since mtDNA copy number is unaffected by DmTTF depletion. This
      work shows conclusively that DmTTF arrests in vivo the progression of the
      mitochondrial RNA polymerase; this is the first ever-obtained evidence for an in
      vivo role of an animal mitochondrial transcription termination factor. In
      addition, the reported data provide interesting insights into the involvement of
      DmTTF in transcription initiation in Drosophila mitochondria.

PMID- 16648358
TI  - Genomic analysis of insertion behavior and target specificity of mini-Tn7 and Tn3
      transposons in Saccharomyces cerevisiae.
AB  - Transposons are widely employed as tools for gene disruption. Ideally, they
      should display unbiased insertion behavior, and incorporate readily into any
      genomic DNA to which they are exposed. However, many transposons preferentially
      insert at specific nucleotide sequences. It is unclear to what extent such bias
      affects their usefulness as mutagenesis tools. Here, we examine insertion site
      specificity and global insertion behavior of two mini-transposons previously used
      for large-scale gene disruption in Saccharomyces cerevisiae: Tn3 and Tn7. Using
      an expanded set of insertion data, we confirm that Tn3 displays marked preference
      for the AT-rich 5 bp consensus site TA[A/T]TA, whereas Tn7 displays negligible
      target site preference. On a genome level, both transposons display marked non
      uniform insertion behavior: certain sites are targeted far more often than
      expected, and both distributions depart drastically from Poisson. Thus, to
      compare their insertion behavior on a genome level, we developed a windowed
      Kolmogorov-Smirnov (K-S) test to analyze transposon insertion distributions in
      sequence windows of various sizes. We find that when scored in large windows
      (>300 bp), both Tn3 and Tn7 distributions appear uniform, whereas in smaller
      windows, Tn7 appears uniform while Tn3 does not. Thus, both transposons are
      effective tools for gene disruption, but Tn7 does so with less duplication and a
      more uniform distribution, better approximating the behavior of the ideal
      transposon.

PMID- 16648359
TI  - The human vitamin D-binding protein gene contains locus control determinants
      sufficient for autonomous activation in hepatic chromatin.
AB  - The human vitamin D-binding protein (hDBP) gene is a member of a cluster that
      includes albumin, alpha-fetoprotein and alpha-albumin genes. The common origin,
      physical linkage and hepatic expression of these four genes predict shared
      regulatory element(s). However, separation of hDBP from the other three genes by
      1.5 Mb argues that hDBP may be under autonomous control. To test for hDBP
      autonomy, mouse lines were generated with a transgene containing the hDBP gene
      along with extensive flanking sequences. Expression of this transgene was
      hepatic, robust and proportional to transgene copy number. DNase I hypersensitive
      site (HS) mapping revealed five liver-specific HS at the hDBP locus: HSI and
      HSIII at -2.1 kb and -0.13 kb upstream of the transcription initiation site, HSIV
      and HSV within intron 1 and HSVII located 3' to the poly(A) site. A second
      transgene with minimal flanking sequences confirmed the sufficiency of these gene
      proximal determinants for hepatic activation. The hepatic-specific HS aligned
      with segments of phylogenetically conserved non-coding sequences. These data
      demonstrate the autonomy of the hDBP locus and suggest that this control is
      mediated by chromatin-based locus control determinants in close proximity to, and
      within the transcription unit.

PMID- 16648360
TI  - Deoxyribozymes that recode sequence information.
AB  - Allosteric nucleic acid ligases have been used previously to transform analyte
      binding into the formation of oligonucleotide templates that can be amplified and
      detected. We have engineered binary deoxyribozyme ligases whose two components
      are brought together by bridging oligonucleotide effectors. The engineered
      ligases can 'read' one sequence and then 'write' (by ligation) a separate,
      distinct sequence, which can in turn be uniquely amplified. The binary
      deoxyribozymes show great specificity, can discriminate against a small number of
      mutations in the effector, and can read and recode DNA information with high
      fidelity even in the presence of excess obscuring genomic DNA. In addition, the
      binary deoxyribozymes can read non-natural nucleotides and write natural sequence
      information. The binary deoxyribozyme ligases could potentially be used in a
      variety of applications, including the detection of single nucleotide
      polymorphisms in genomic DNA or the identification of short nucleic acids such as
      microRNAs.

PMID- 16648361
TI  - The molecular mechanism of DNA damage recognition by MutS homologs and its
      consequences for cell death response.
AB  - We determined the molecular mechanism of cell death response by MutS homologs in
      distinction to the repair event. Key protein-DNA contacts differ in the
      interaction of MutS homologs with cisplatinated versus mismatched DNA. Mutational
      analyses of protein-DNA contacts, which were predicted by molecular dynamics (MD)
      simulations, were performed. Mutations in suggested interaction sites can affect
      repair and cell death response independently, and to different extents. A
      glutamate residue is identified as the key contact with cisplatin-DNA. Mutation
      of the residue increases cisplatin resistance due to increased non-specific DNA
      binding. In contrast, the conserved phenylalanine that is instrumental and
      indispensable for mismatch recognition during repair is not required for
      cisplatin cytotoxicity. These differences in protein-DNA interactions are
      translated into localized conformational changes that affect nucleotide
      requirements and inter-subunit interactions. Specifically, the ability for ATP
      binding/hydrolysis has little consequence for the MMR-dependent damage response.
      As a consequence, intersubunit contacts are altered that most likely affect the
      interaction with downstream proteins. We here describe the interaction of MutS
      homologs with DNA damage, as it differs from the interaction with a mismatch, and
      its structural translation into all other functional regions of the protein as a
      mechanism to initiate cell death response and concomitantly inhibit repair.

PMID- 16648362
TI  - Crystallographic identification of an ordered C-terminal domain and a second
      nucleotide-binding site in RecA: new insights into allostery.
AB  - RecA protein is a crucial and central component of the homologous recombination
      and DNA repair machinery. Despite numerous studies on the protein, several issues
      concerning its action, including the allosteric regulation mechanism have
      remained unclear. Here we report, for the first time, a crystal structure of a
      complex of Mycobacterium smegmatis RecA (MsRecA) with dATP, which exhibits a
      fully ordered C-terminal domain, with a second dATP molecule bound to it. ATP
      binding is an essential step for all activities of RecA, since it triggers the
      formation of active nucleoprotein filaments. In the crystal filament, dATP at the
      first site communicates with a dATP of the second site of an adjacent subunit,
      through conserved residues, suggesting a new route for allosteric regulation. In
      addition, subtle but definite changes observed in the orientation of the
      nucleotide at the first site and in the positions of the segment preceding loop
      L2 as well as in the segment 102-105 situated between the 2 nt, all appear to be
      concerted and suggestive of a biological role for the second bound nucleotide.

PMID- 16648363
TI  - Structural stabilization of GTP-binding domains in circularly permuted GTPases:
      implications for RNA binding.
AB  - GTP hydrolysis by GTPases requires crucial residues embedded in a conserved G
      domain as sequence motifs G1-G5. However, in some of the recently identified
      GTPases, the motif order is circularly permuted. All possible circular
      permutations were identified after artificially permuting the classical GTPases
      and subjecting them to profile Hidden Markov Model searches. This revealed G4-G5
      G1-G2-G3 as the only possible circular permutation that can exist in nature. It
      was also possible to recognize a structural rationale for the absence of other
      permutations, which either destabilize the invariant GTPase fold or disrupt
      regions that provide critical residues for GTP binding and hydrolysis, such as
      Switch-I and Switch-II. The circular permutation relocates Switch-II to the C
      terminus and leaves it unfastened, thus affecting GTP binding and hydrolysis.
      Stabilizing this region would require the presence of an additional domain
      following Switch-II. Circularly permuted GTPases (cpGTPases) conform to such a
      requirement and always possess an 'anchoring' C-terminal domain. There are four
      sub-families of cpGTPases, of which three possess an additional domain N-terminal
      to the G-domain. The biochemical function of these domains, based on available
      experimental reports and domain recognition analysis carried out here, are
      suggestive of RNA binding. The features that dictate RNA binding are unique to
      each subfamily. It is possible that RNA-binding modulates GTP binding or vice
      versa. In addition, phylogenetic analysis indicates a closer evolutionary
      relationship between cpGTPases and a set of universally conserved bacterial
      GTPases that bind the ribosome. It appears that cpGTPases are RNA-binding
      proteins possessing a means to relate GTP binding to RNA binding.

PMID- 16648364
TI  - A sequence motif conserved in diverse nuclear proteins identifies a protein
      interaction domain utilised for nuclear targeting by human TFIIS.
AB  - The three structural domains of transcription elongation factor TFIIS are
      conserved from yeast to human. Although the N-terminal domain is not needed for
      transcriptional activity, a similar sequence has been identified previously in
      other transcription factors. We found this conserved sequence, the LW motif, in
      another three human proteins that are predominantly nuclear localized. We
      investigated two examples to determine whether the LW motif is actually a
      dedicated nuclear targeting signal. However, in one of the newly identified
      proteins, hIWS1 (human Iws1), a region containing classic nuclear localization
      signals (NLS) rather than the LW motif was necessary and sufficient for nuclear
      targeting in HeLa cells. In contrast, human TFIIS does not possess an NLS and
      only constructs containing the LW motif were efficiently targeted to nuclei.
      Moreover, mutations in the motif could cause cytoplasmic accumulation of TFIIS
      and enabled a structure/function assay for the domain based on the efficiency of
      nuclear targeting. Finally, GST pull-down assays showed that the LW motif is part
      of a protein-binding domain. We suggest that the targeting role the LW motif
      plays in TFIIS arises from its more general function as a protein interaction
      domain, enabling TFIIS to bind a carrier protein(s) that accomplishes nuclear
      import.

PMID- 16648365
TI  - The phosphatase activity of mammalian polynucleotide kinase takes precedence over
      its kinase activity in repair of single strand breaks.
AB  - The dual function mammalian DNA repair enzyme, polynucleotide kinase (PNK),
      facilitates strand break repair through catalysis of 5'-hydroxyl phosphorylation
      and 3'-phosphate dephosphorylation. We have examined the relative activities of
      the kinase and phosphatase functions of PNK using a novel assay, which allows the
      simultaneous characterization of both activities in processing nicks and gaps
      containing both 3'-phosphate and 5'-hydroxyl. Under multiple turnover conditions
      the phosphatase activity of the purified enzyme is significantly more active than
      its kinase activity. Consistent with this result, phosphorylation of the 5'
      hydroxyl is rate limiting in cell extract mediated-repair of a nicked substrate.
      On characterizing the effects of individually mutating the two active sites of
      PNK we find that while site-directed mutagenesis of the kinase domain of PNK does
      not affect its phosphatase activity, disruption of the phosphatase domain also
      abrogates kinase function. This loss of kinase function requires the presence of
      a 3'-phosphate, but it need not be present in the same strand break as the 5'
      hydroxyl. PNK preferentially binds 3'-phosphorylated substrates and DNA binding
      to the phosphatase domain blocks further DNA binding by the kinase domain.

PMID- 16648366
TI  - Petunia phospholipase c1 is involved in pollen tube growth.
AB  - Although pollen tube growth is essential for plant fertilization and reproductive
      success, the regulators of the actin-related growth machinery and the cytosolic
      Ca2+ gradient thought to determine how these cells elongate remain poorly
      defined. Phospholipases, their substrates, and their phospholipid turnover
      products have been proposed as such regulators; however, the relevant
      phospholipase(s) have not been characterized. Therefore, we cloned cDNA for a
      pollen-expressed phosphatidylinositol 4,5-bisphosphate (PtdInsP2)-cleaving
      phospholipase C (PLC) from Petunia inflata, named Pet PLC1. Expressing a
      catalytically inactive form of Pet PLC1 in pollen tubes caused expansion of the
      apical Ca2+ gradient, disruption of the organization of the actin cytoskeleton,
      and delocalization of growth at the tube tip. These phenotypes were suppressed by
      depolymerizing actin with low concentrations of latrunculin B, suggesting that a
      critical site of action of Pet PLC1 is in regulating actin structure at the
      growing tip. A green fluorescent protein (GFP) fusion to Pet PLC1 caused
      enrichment in regions of the apical plasma membrane not undergoing rapid
      expansion, whereas a GFP fusion to the PtdInsP2 binding domain of mammalian PLC
      delta1 caused enrichment in apical regions depleted in PLC. Thus, Pet PLC1
      appears to be involved in the machinery that restricts growth to the very apex of
      the elongating pollen tube, likely through its regulatory action on PtdInsP2
      distribution within the cell.

PMID- 16648367
TI  - Maintenance of DNA methylation during the Arabidopsis life cycle is essential for
      parental imprinting.
AB  - Imprinted genes are expressed predominantly from either their paternal or their
      maternal allele. To date, all imprinted genes identified in plants are expressed
      in the endosperm. In Arabidopsis thaliana, maternal imprinting has been clearly
      demonstrated for the Polycomb group gene MEDEA (MEA) and for FWA. Direct repeats
      upstream of FWA are subject to DNA methylation. However, it is still not clear to
      what extent similar cis-acting elements may be part of a conserved molecular
      mechanism controlling maternally imprinted genes. In this work, we show that the
      Polycomb group gene FERTILIZATION-INDEPENDENT SEED2 (FIS2) is imprinted.
      Maintenance of FIS2 imprinting depends on DNA methylation, whereas loss of DNA
      methylation does not affect MEA imprinting. DNA methylation targets a small
      region upstream of FIS2 distinct from the target of DNA methylation associated
      with FWA. We show that FWA and FIS2 imprinting requires the maintenance of DNA
      methylation throughout the plant life cycle, including male gametogenesis and
      endosperm development. Our data thus demonstrate that parental genomic imprinting
      in plants depends on diverse cis-elements and mechanisms dependent or independent
      of DNA methylation. We propose that imprinting has evolved under constraints
      linked to the evolution of plant reproduction and not by the selection of a
      specific molecular mechanism.

PMID- 16648368
TI  - Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors
      restitute hypertensive internal anal sphincter in the spontaneously hypertensive
      rats.
AB  - The present study determined the effects of the angiotensin-converting enzyme
      (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT1-R)
      antagonist losartan on the internal anal sphincter pressures (IASP) in
      spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats
      (WKY). The SHR had significantly higher IASP (21.7 +/- 0.8 mm Hg) than the WKY
      (14.7 +/- 0.9 mm Hg), which was associated with the higher levels of angiotensin
      II (Ang II) in plasma (50.3 +/- 0.9 pg/ml) and in muscle bath perfusates (72.7 +/
      11.8 pg/ml) compared with the WKY (p < 0.05). Captopril and losartan decreased
      the IASP in SHR and WKY, but they were more potent in SHR. Captopril and losartan
      normalized the IASP in the SHR, whereas these agents may compromise rectoanal
      continence in the WKY. Reverse transcriptase-polymerase chain reaction and
      Western blots showed higher levels of angiotensinogen, renin, ACE, and AT1-R in
      the internal anal sphincter (IAS) of SHR. Ang II caused concentration-dependent
      contraction of IAS smooth muscle strips from WKY (pEC50 = 8.5 +/- 0.1) and SHR
      (pEC50 = 8.6 +/- 0.2). Losartan (100 nM) significantly (p < 0.05) inhibited this
      effect. From these data, we conclude that 1) hypertensive IAS in SHR is primarily
      the result of renin-angiotensin system up-regulation, 2) ACE inhibitors and AT(1)
      R antagonists simply relieve the hypertensive IAS, and 3) the differential effect
      of these inhibitors in the hypertensive versus the normotensive IAS may explain
      the lack of incontinence as a side effect in hypertensive patients receiving ACE
      inhibitors and AT1-R antagonists.

PMID- 16648369
TI  - The dopamine stabilizers (S)-(-)-(3-methanesulfonyl-phenyl)-1-propyl-piperidine
      [(-)-OSU6162] and 4-(3-methanesulfonylphenyl)-1-propyl-piperidine (ACR16) show
      high in vivo D2 receptor occupancy, antipsychotic-like efficacy, and low
      potential for motor side effects in the rat.
AB  - "Dopamine stabilizers" are a new class of compounds that have the ability to
      reverse both hypo- as well as hyperdopaminergia in vivo. This class, exemplified
      by the phenylpiperidines (S)-(-)-3-(3-methanesulfonyl-phenyl)-1-propyl-piperidine
      [(-)-OSU6162] and 4-(3-methanesulfonyl-phenyl)-1-propyl)-piperidine [ACR16]
      although lacking high in vitro binding affinity for dopamine D2 receptor [(-)
      OSU6162, Ki = 447 nM; ACR16, Ki > 1 microM], shows functional actions, suggestive
      of their interaction. Hence, we evaluated in vivo D2 occupancy of these agents in
      rats and correlated it to observed effects in a series of behavioral,
      neurochemical, and endocrine models relevant to the dopamine system and
      antipsychotic effect. Both (-)-OSU6162 and ACR16 showed robust dose-dependent
      striatal D2 occupancy with ED50 values of 5.27 and 18.99 mg/kg s.c.,
      respectively, and functional assays showed no partial agonism. Over an occupancy
      range of 37 to 87% (3-60 mg/kg) for (-)-OSU6162 and 35 to 74% (10-60 mg/kg) for
      ACR16, we observed both inhibitory (amphetamine-induced locomotor activity) and
      stimulatory effects (in habituated rats). Haloperidol, over a similar occupancy
      range (33-78%), potently inhibited psychostimulant activity and induced
      catalepsy, but it failed to activate habituated animals. In the conditioned
      avoidance response assay, ACR16 was clearly more efficacious than (-)-OSU6162. In
      addition, both these compounds demonstrated significant preferential Fos
      induction in the nucleus accumbens compared with the dorsolateral striatum, a
      strong predictor of atypical antipsychotic efficacy. The results suggest that
      dopamine stabilizers exhibit locomotor stabilizing as well as antipsychotic-like
      effects, with low motor side effect liability, in a dose range that corresponds
      to high D2 in vivo occupancy.

PMID- 16648370
TI  - Novel glucagon-like peptide-1 (GLP-1) analog (Val8)GLP-1 results in significant
      improvements of glucose tolerance and pancreatic beta-cell function after 3-week
      daily administration in obese diabetic (ob/ob) mice.
AB  - This study evaluates the antidiabetic potential of an enzyme-resistant analog,
      (Val8)GLP-1. The effects of daily administration of a novel dipeptidyl peptidase
      IV-resistant glucagon-like peptide-1 (GLP-1) analog, (Val8)GLP-1, on glucose
      tolerance and pancreatic beta-cell function were examined in obese-diabetic
      (ob/ob) mice. Acute intraperitoneal administration of (Val8)GLP-1 (6.25-25
      nmol/kg) with glucose increased the insulin response and reduced the glycemic
      excursion in a dose-dependent manner. The effects of (Val8)GLP-1 were greater and
      longer lasting than native GLP-1. Once-daily subcutaneous administration of
      (Val8)GLP-1 (25 nmol/kg) for 21 days reduced plasma glucose concentrations,
      increased plasma insulin, and reduced body weight more than native GLP-1 without
      a significant change in daily food intake. Furthermore, (Val8)GLP-1 improved
      glucose tolerance, reduced the glycemic excursion after feeding, increased the
      plasma insulin response to glucose and feeding, and improved insulin sensitivity.
      These effects were consistently greater with (Val8)GLP-1 than with native GLP-1,
      and both peptides retained or increased their acute efficacy compared with
      initial administration. (Val8)GLP-1 treatment increased average islet area 1.2
      fold without changing the number of islets, resulting in an increased number of
      larger islets. These data demonstrate that (Val8)GLP-1 is more effective and
      longer acting than native GLP-1 in obese-diabetic ob/ob mice.

PMID- 16648371
TI  - LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers
      syndrome.
AB  - BACKGROUND: LKB1/STK11 germline mutations cause Peutz-Jeghers syndrome (PJS). The
      existence of a second PJS locus is controversial, the evidence in its favour
      being families unlinked to LKB1 and the low frequency of LKB1 mutations found
      using conventional methods in several studies. Exonic and whole gene deletion or
      duplication events cannot be detected by routine mutation screening methods.
      OBJECTIVE: To seek evidence for LKB1 germline deletions or duplications by
      screening patients meeting clinical criteria for PJS but without detected
      mutations on conventional screening. METHODS: From an original cohort of 76
      patients, 48 were found to have a germline mutation by direct sequencing; the
      remaining 28 were examined using multiplex ligation dependent probe amplification
      (MLPA) analysis to detect LKB1 copy number changes. RESULTS: Deletions were found
      in 11 of the 28 patients (39%)--that is, 14% of all PJS patients (11/76). Five
      patients had whole gene deletions, two had the promoter and exon 1 deleted, and
      in one patient exon 8 was deleted. Other deletions events involved: loss of exons
      2-10; deletion of the promoter and exons 1-3; and loss of part of the promoter.
      No duplications were detected. Nine samples with deletions were sequenced at
      reported single nucleotide polymorphisms to exclude heterozygosity; homozygosity
      was found in all cases. No MLPA copy number changes were detected in 22 healthy
      individuals. CONCLUSIONS: These results lessen the possibility of a second PJS
      locus, as the detection rate of germline mutations in PJS patients was about 80%
      (59/76). It is suggested that MLPA, or a suitable alternative, should be used for
      routine genetic testing of PJS patients in clinical practice.

PMID- 16648372
TI  - Inversion polymorphisms and non-contiguous terminal deletions: the cause and the
      (unpredicted) effect of our genome architecture.
AB  - Molecular definition at the BAC level of an 8p dicentric chromosome and an 8p
      deleted chromosome is reported in a patient with two different cell lines. The
      dicentric, which differed from that generating the recurrent inv dup del(8p) for
      the location of its break point, originated during the paternal meiosis on the
      background of the classical 8p23.1 inversion polymorphism. The breakage of this
      dicentric gave rise to the 8p deleted chromosome which, as a result of the
      inversion, had two non-contiguous deletions. These findings confirm previous data
      on 1p distal deletions, showing that at least some of the deletions stem from the
      breakage of dicentric chromosomes. They suggest that non-contiguous deletions may
      be frequent among distal deletions. This type of rearrangement can easily be
      overlooked when two contiguous clones, one absent and the other present by FISH
      analysis, are taken as boundaries of the deletion break point; in this case only
      high resolution array-CGH will reveal their real frequency. The definition of
      such non-contiguous distal deletions is relevant for phenotype/karyotype
      correlations. There are historical examples of blunders caused by overlooking a
      second non-contiguous deletion. This paper shows how small scale structural
      variations, such as common polymorphic inversions, may cause complex
      rearrangements such as terminal deletions.

PMID- 16648373
TI  - Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1.
AB  - BACKGROUND: High myopia is a common genetic variation in most cases, affecting 1
      2% of people, and is the fourth most common disorder causing blindness worldwide.
      Six autosomal dominant loci and one X-linked recessive locus have been reported,
      but no genes responsible for high myopia have been identified. OBJECTIVE: To
      report a Chinese family in which six males presented with high myopia consistent
      with an X linked recessive trait. RESULTS: Affected individuals shared three
      common features: high myopia, reduced visual acuity, and fundal changes of high
      myopia. Protan and deutan were observed in the family, but they did not co
      segregate with the high myopia phenotype. X-chromosome-wide linkage analysis
      mapped the high myopia locus to a 25 cM (14.9 Mb) region on Xq23-q25 between
      DXS1210 and DXS8057, with maximum two point lod scores at theta = 0 of 2.75 and
      2.29 for DXS1001 and DXS8059, respectively. CONCLUSIONS: This new myopia locus is
      outside the linked region of the first high myopia locus (MYP1). Refinement of
      the linkage region with additional families and screening candidate genes for
      mutation may lead to the identification of the defect gene.

PMID- 16648374
TI  - Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism.
AB  - OBJECTIVE: To screen cDNA for NLGN3 and NLGN4 from lymphoblastoid cells from
      autistic subjects. METHODS AND RESULTS: 10 young autistic females and 30 non
      autistic subjects were studied for alterations in two X linked genes, NLGN3 and
      NLGN4. A novel NLGN4 isoform lacking exon 4, which occurred de novo on the
      paternal allele, was identified in one of the autistic females. Monoallelic
      expression of NLGN4 was seen in this subject and in 11 of 14 informative autistic
      and non-autistic females using a single nucleotide polymorphism found at 3' UTR.
      Additionally, the NLGN3 transcript was present in two isoforms (with and without
      exon 7) in nine of 10 autistic females and in 30 non-autistic subjects, including
      parents of the autistic female having only the complete transcript with exon 7,
      and from the whole brain of a control. The novel truncated NLGN3 product may have
      a regulatory role, as reported in other proteins (for example, vasopressin
      receptor) by attenuating the function of the full length isoform, resulting in a
      reduction of the mature protein. Three dimensional protein structures were
      characterised using comparative modelling, and significant changes were suggested
      in the protein cores for these two neuroligin isoforms. CONCLUSIONS: Splice
      variants may lead to potentially abnormal neuroligins in the causation of autism
      spectrum disorders.

PMID- 16648375
TI  - Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome.
AB  - Cohen syndrome (CS) is an autosomal recessive disorder with variability in the
      clinical manifestations, characterised by mental retardation, postnatal
      microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and
      intermittent neutropenia. Mutations in the gene COH1 have been found in an
      ethnically diverse series of patients. Brief clinical descriptions of 24 patients
      with CS are provided. The patients were from 16 families of different ethnic
      backgrounds and between 2.5 and 60 years of age at assessment. DNA samples from
      all patients were analysed for mutations in COH1 by direct sequencing. Splice
      site mutations were characterised using reverse transcriptase PCR analysis from
      total RNA samples. In this series, we detected 25 different COH1 mutations; 19 of
      these were novel, including 9 nonsense mutations, 8 frameshift mutations, 4
      verified splice site mutations, 3 larger in frame deletions, and 1 missense
      mutation. We observed marked variability of developmental and growth parameters.
      The typical facial gestalt was seen in 23/24 patients. Early onset progressive
      myopia was present in all the patients older than 5 years. Widespread pigmentary
      retinopathy was found in 12/14 patients assessed over 5 years of age. We present
      evidence for extended allelic heterogeneity of CS, with the vast majority of
      mutations leading to premature termination codons in COH1. Our data confirm the
      broad clinical spectrum of CS with some patients lacking even the characteristic
      facial gestalt and pigmentary retinopathy at school age.

PMID- 16648376
TI  - Oculopharyngeal muscular dystrophy: a point mutation which mimics the effect of
      the PABPN1 gene triplet repeat expansion mutation.
AB  - BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant
      late onset neuromuscular disease characterised by proximal muscle weakness,
      ptosis, and swallowing difficulty. The only causative mutation described to date
      is a triplet repeat expansion consisting of two to seven additional base triplets
      in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1
      (PABPN1) gene. This results in an increase in length of a polyalanine tract in
      the PABPN1 protein from 10 to 12-17 residues. OBJECTIVE: Description of another
      mutation in a case of OPMD. METHODS: Sequence analysis of exon 1 of the PABPN1
      gene was undertaken on 202 patients referred for a possible diagnosis of OPMD but
      negative for the triplet repeat expansion mutation. RESULTS: A case was
      identified with typical symptoms of OPMD, negative for the repeat expansion
      mutation but with a missense mutation in PABPN1 close to the 3' end of the normal
      polyalanine codon repeat sequence. CONCLUSIONS: The single base mutation changes
      a glycine codon to an alanine codon and results in an increase in the number of
      contiguous polyalanine codons. This mimics the effect of the common triplet
      repeat expansion mutation and represents a previously undescribed mechanism of
      mutation.

PMID- 16648377
TI  - Mutations responsible for Larsen syndrome cluster in the FLNB protein.
AB  - BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were
      reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB,
      could explain the disease in our independent collection of sporadic and dominant
      Larsen syndrome cases; and to test whether mutations occurred in a non-random
      pattern. RESULTS: Missense mutations were found in each of five cases. Four of
      the five were new; one was reported in a sporadic case in the original Larsen
      syndrome study of five cases. All mutations from the two studies were compiled.
      Clustered mutations were observed within three filamin B protein domains: the
      calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few
      as five (of the total of 46) coding exons of FLNB could be screened to detect
      Larsen syndrome mutations. Four of these exons were screened in a sixth
      (sporadic) case and a previously reported G1691S substitution mutation detected.
      CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen
      syndrome. They appear to occur in specific functional domains of the filamin B
      protein. This should simplify diagnostic screening of the FLNB gene. Analyses in
      larger patient series are warranted to quantify this. The study confirmed the
      extreme variability in clinical presentation and the presence of unaffected
      carriers. A molecular screen would be valuable for diagnosis and genetic
      counselling.

PMID- 16648379
TI  - Patients who deceive.

PMID- 16648378
TI  - Autosomal dominant optic atrophy associated with hearing impairment and impaired
      glucose regulation caused by a missense mutation in the WFS1 gene.
AB  - Autosomal dominant optic atrophy (ADOA) is genetically heterogeneous, with OPA1
      on 3q28 being the most prevalently mutated gene. Additional loci are OPA3, OPA4,
      and OPA5, located at 19q13.2, 18q12.2, and 22q12.1-q13.1, respectively. Mutations
      in the WFS1 gene, at 4p16.3, are associated with either optic atrophy (OA) as
      part of the autosomal recessive Wolfram syndrome or with autosomal dominant
      progressive low frequency sensorineural hearing loss (LFSNHL) without any
      ophthalmological abnormalities. Linkage and sequence mutation analyses of the
      ADOA candidate genes OPA1, OPA3, OPA4, and OPA5, including the genes WFS1, GJB2,
      and GJB6 associated with recessive inherited OA or dominant LFSNHL, were
      performed. We identified one novel WFS1 missense mutation E864K, c.2590G-->A in
      exon 8 that co-segregates with ADOA combined with hearing impairment and impaired
      glucose regulation. This is the first example of autosomal dominant optic atrophy
      and hearing loss associated with a WFS1 mutation, supporting the notion that
      mutations in WFS1 as well as in OPA1 may lead to ADOA combined with impaired
      hearing.

PMID- 16648380
TI  - A case of Munchausen syndrome by proxy with subsequent stalking behavior.
AB  - A case of Munchausen syndrome by proxy (factitious disorder by proxy) wherein the
      patient presented with symptoms of severe borderline personality disorder and
      questionable psychotic symptoms is discussed. This patient was also adjudicated
      for harassing and stalking a child protective services worker assigned to her
      case. Issues pertaining to possible feigning of psychotic symptoms were addressed
      in her inpatient treatment. Despite doubts concerning the veracity of some of her
      psychotic symptoms, the patient responded well to clozapine, and she was
      subsequently able to stay out of the psychiatric hospital for longer periods and
      make a reasonably good adjustment to living in a group home. After refusing to
      continue with clozapine therapy because of weight gain concerns, her adjustment
      declined.

PMID- 16648381
TI  - The terrorist mind: II. Typologies, psychopathologies, and practical guidelines
      for investigation.
AB  - Part I of this two-part article presents a psychological and political analysis
      of the terrorist mind. Part II describes the major current psychological
      classifications and typologies of domestic and foreign terrorism. Explanations
      are offered in terms of our current understanding of the personality and
      psychopathology of terroristic violence. A heuristic model of classifying
      terrorism in terms of personality and psychopathology is presented. In addition
      to guiding further research and theory on the psychology of terrorism, this model
      has immediate practical application to the investigation and interrogation of
      terrorist suspects.

PMID- 16648382
TI  - Correlates of subjective stress among drug court clients.
AB  - Psychosocial stress is consistently found to promote initiation, intensification,
      and relapse in drug abuse. It would, therefore, be desirable to identify
      characteristics of offenders who are at heightened risk for stress-induced
      exacerbations of addictive behavior. In this cross-sectional, correlational,
      interview study, 500 clients of two Kentucky drug courts averaged 30 years of age
      and were predominantly male, White, employed, high school educated, single, and
      adjudicated in small- and medium-size cities. Five independent correlates of
      greater subjective stress emerged in stepwise multiple regression analysis (R2 =
      .395): use of escape-avoidance coping, positive reappraisal coping (inversely
      associated), more negative life events, better self-rated health (inversely
      associated), and access to social support related to work problems (inversely
      associated). Treatment interventions emphasizing effective coping styles and
      building of social support as well as managing of negative life events and
      perceptions of health may serve to lessen subjective stress and its consequences
      in drug-abusing criminal populations.

PMID- 16648383
TI  - Are effective drug courts an urban phenomenon?: considering their impact on
      recidivism among a nonmetropolitan adult sample in Washington State.
AB  - Drug courts represent a significant development in criminal justice during the
      past 15 years, and a small but growing literature suggests they are effective in
      reducing drug use and criminal behavior. Most of these studies evaluate the
      effects of drug courts in urban areas, however. This study adds to this
      literature by considering the effects of this intermediate sanction among adult
      offenders in a small, nonmetropolitan county of northwest Washington. Using a
      retrospective comparison group of matched control participants, these results
      show that the prevalence and incidence of rearrest is significantly lower among
      drug court graduates than probationers. These differences in recidivism persist
      even when the age, race, gender, and number of days at risk in the community are
      statistically controlled. Among those who did recidivate, drug court graduates
      did not significantly differ from controls in duration to first arrest and arrest
      incidence. Policy implications are discussed.

PMID- 16648384
TI  - The Personal Concerns Inventory (Offender Adaptation): measuring and enhancing
      motivation to change.
AB  - Measuring offenders' motivation for treatment is important for selection and
      monitoring treatment engagement, yet few psychometrically robust measures of
      motivation exist. The Personal Concerns Inventory (PCI) was developed to assess
      motivation to change in people with addictive behaviours. It focuses on
      identifying goals in a wide variety of life areas, and two profiles have
      consistently been identified--adaptive and maladaptive. This study aimed to adapt
      the PCI for use with offenders and assess its suitability. Following amendment,
      11 men serving prison sentences were interviewed using the PCI (Offender
      Adaptation, OA). Personal concerns related to self-change, and partner, family,
      and relationships were most commonly identified. Scores suggested that offenders
      show adaptive and maladaptive profiles, similar to those previously identified.
      The PCI (OA) has promise for use with offenders, although the issue of whether
      the PCI (OA) is better viewed as a measure of motivation or a motivational
      enhancer remains for further research.

PMID- 16648385
TI  - Social support, spiritual program, and addiction recovery.
AB  - This study compared personal and emotional modifications of inmates who were
      recovering addicts and who participated in one of two year-long therapeutic
      intervention programs, one including social support and experiential spiritual
      program components (Narcotics Anonymous, NA, meetings and the 12-step course),
      the other including primarily social support (NA meetings only, without the 12
      step program). The hypothesis was that supplementing social support programs with
      a concrete spiritual program would result in more positive personal and emotional
      changes. The results seem to support the hypothesis: Inmates participating in the
      12-step program demonstrated a higher sense of coherence and meaning in life and
      a gradual reduction in the intensity of negative emotions (anxiety, depression,
      and hostility) than those participating in NA meetings without the 12-step
      program. The research findings demonstrate the importance of the 12-step program
      as part of a rehabilitation process for drug addicts.

PMID- 16648386
TI  - Facing rejection: new relationships, broken relationships, shame, and stalking.
AB  - This study provides a preliminary examination of the relationship among shame
      proneness, emotions, and persistent, unwanted courting or pursuit behaviour. A
      total of 222 undergraduates completed a questionnaire measuring responses to the
      termination of a relationship or the declining of a date. The Test of Self
      Conscious Affect was used to measure shame. Although shame was unrelated to types
      of intrusive behaviour, individuals who engaged more repetitively in covert
      pursuit tended to ruminate more over their love interest than did those who
      rarely engaged in such behaviour. Rumination was positively correlated with
      shame. Self-harm behaviours and harm toward others were associated with feelings
      of sadness and depression, and those who engaged more often in harm toward others
      also reported feelings of anger and jealousy. Conclusions are made regarding the
      function of shame and other emotions in intrusive behaviour and their potential
      relevance to treatment of stalkers.

PMID- 16648387
TI  - Is schizoid personality a forerunner of homicidal or suicidal behavior?: a case
      study.
AB  - The authors believe that a relationship exists between schizoid personality
      disorder and violent acts. The following case study is presented to contemplate
      such a possible relationship. There is a paucity of research on this topic. The
      authors suggest that further research closely examine the relationship between
      violent behavior and those character traits associated with schizoid personality
      disorder. If such a relationship is found, these character traits could be
      integrated with other risk factors known to predict violence.

PMID- 16648388
TI  - Validities and abilities in criminal profiling: a critique of the studies
      conducted by Richard Kocsis and his colleagues.
AB  - In a recent issue of this journal, Kocsis reviewed the criminal profiling
      research that he and his colleagues have conducted during the past 4 years. Their
      research examines the correlates of profile accuracy with respect to the skills
      of the individual constructing the profile, and it has led Kocsis to draw
      conclusions that are important to the profiling field. In this article, the
      authors review the contributions of the Kocsis studies and critique their
      methodological and conceptual foundations. The authors raise a number of concerns
      and argue that data from the Kocsis studies fail to support many of the
      conclusions presented in his recent review. The authors present evidence in
      support of their assertions and provide recommendations that will allow future
      research in the area to generate data that are more meaningful and generalizable.

PMID- 16648389
TI  - CYP2C76, a novel cytochrome P450 in cynomolgus monkey, is a major CYP2C in liver,
      metabolizing tolbutamide and testosterone.
AB  - Monkeys are widely used as a primate model to study drug metabolism because they
      generally show a metabolic pattern similar to humans. However, the paucity of
      information on cytochrome P450 (P450) genes has hampered a deep understanding of
      drug metabolism in the monkey. In this study, we report identification of the
      CYP2C76 cDNA newly identified in cynomolgus monkey and characterization of this
      CYP2C along with cynomolgus CYP2C20, CYP2C43, and CYP2C75. The CYP2C76 cDNA
      contains the open reading frame encoding a protein of 489 amino acids that are
      only approximately 80% identical to any human or monkey P450 cDNAs. Gene and
      protein expression of CYP2C76 was confirmed in the liver of cynomolgus and rhesus
      monkeys but not in humans or the great apes. Moreover, CYP2C76 is located at the
      end of the CYP2C gene cluster in the monkey genome, the region of which
      corresponds to the intergenic region adjacent to the CYP2C cluster in the human
      genome, strongly indicating that this gene does not have the ortholog in humans.
      Among the four CYP2C genes expressing predominantly in the liver, the expression
      level of CYP2C76 was the greatest, suggesting that CYP2C76 is a major CYP2C in
      the monkey liver. Assays for the capacity of CYP2C76 to metabolize drugs using
      several substrates typical for human CYP2Cs revealed that CYP2C76 showed unique
      metabolic activity. These results suggest that CYP2C76 contributes to overall
      drug-metabolizing activity in the monkey liver and might account for species
      difference occasionally seen in drug metabolism between monkeys and humans.

PMID- 16648390
TI  - Social networks and self-rated health: a cross-cultural examination among older
      Israelis.
AB  - OBJECTIVE: This article examines the relationship of social network and self
      rated health among different cultural groups. METHODS: This study examined
      associations between network structure, interaction, support and social
      engagement and self-rated health, controlling for sociodemographic background and
      psychobiological pathways among veteran Jewish-Israelis (n = 2,043), Arab
      Israelis (n = 609), and new immigrants from the former Soviet Union (n = 751).
      Hierarchical multiple regression analysis was performed. RESULTS: Three different
      patterns emerged. The association of social network and self-rated health among
      the majority veteran Jewish culture in Israel was similar to that found in
      Western societies. Among Arab-Israelis, self-rated health was explained by more
      traditional, familial, and communal network dynamics. The characteristic
      association between social network and self-rated health among the new immigrants
      was explained by migration-induced factors. DISCUSSION: The findings demonstrate
      that social networks impact health differently in different cultural groups and
      under conditions of social change, such as migration in later-life.

PMID- 16648391
TI  - The relation of social isolation, loneliness, and social support to disease
      outcomes among the elderly.
AB  - OBJECTIVE: This study examined relations between social isolation, loneliness,
      and social support to health outcomes in a sample of New Mexico seniors. METHOD:
      We used random-digit dialing to obtain a random sample of 755 southern New Mexico
      seniors. Participants answered questions pertaining to demographics, social
      isolation and loneliness, social support, and disease diagnosis including
      diabetes, hypertension, heart disease, liver disease, arthritis, emphysema,
      tuberculosis, kidney disease, cancer, asthma, and stroke. The sample allowed for
      comparison of Caucasian and Hispanic participants. RESULTS: Correlational and
      logistic analyses indicated that belongingness support related most consistently
      to health outcomes. Ethnic subgroup analysis revealed similarities and
      differences in the pattern of associations among the predictor and outcome
      variables. DISCUSSION: The results demonstrate the importance of social variables
      for predicting disease outcomes in the elderly and across ethnic groups.

PMID- 16648392
TI  - The role of conflict resolution styles on nursing staff morale, burnout, and job
      satisfaction in long-term care.
AB  - This study focuses on the ability of nursing staff to interact with residents in
      a way that affects positively on the nurses' well-being and occupational
      satisfaction. It investigates the role of coping skills related to staff-resident
      interactions, in particular, the use of conflict resolution styles and their
      influence on the level of morale, burnout and job satisfaction of nursing
      professionals. A self-administered questionnaire was used to collect information
      from 161 direct care nursing staff. The authors used a multiple regression
      procedure to examine the influence of predictors on nursing staff outcomes.
      Multivariate analyses indicated that nurses' psychological morale, occupational
      stress, and job satisfaction are influenced by conflict resolution styles, after
      controlling by individual characteristics, work demands, and work resources
      factors. The findings highlight the importance of considering personal coping
      abilities to foster positive staff-resident interactions and to increase nurses'
      morale and job satisfaction.

PMID- 16648393
TI  - The negative association of independent personality and medication adherence.
AB  - OBJECTIVE: This investigation examines the association of personality factors and
      medication adherence among older adults. METHOD: The Six-Factor Personality
      Questionnaire was mailed to participants involved in a medication adherence
      investigation. Medication adherence was monitored with an electronic monitoring
      cap for 8 weeks for one prescribed daily medication. RESULTS: Sixty older adults,
      mean age 77 years (range 67 to 93 years), returned the questionnaire (69%
      response rate). Stepwise regression analysis demonstrates that when age and level
      of education are controlled, independence predicts medication adherence. This
      factor demonstrates a negative relationship with adherence suggesting that higher
      levels of independence may be related to lower adherence to prescribed
      medication. The facet component self-reliance is predictive of poor medication
      adherence. DISCUSSION: The finding that higher self-reliance is associated with
      lower adherence in an older population deserves further investigation and
      clinical consideration.

PMID- 16648394
TI  - Social capital and quality of life in old age: results from a cross-sectional
      study in rural Bangladesh.
AB  - The objective of this article is to identify determinants of quality of life
      (QoL) and investigate their association with individual- and community-level
      social capital among older people in rural Bangladesh. A cross-sectional study of
      1,135 elderly persons (aged >/= 60 years) was conducted in a rural district in
      Bangladesh. Independent variables included age, sex, education, economic status
      of the elderly person, and individual- and community-level social capital. Self
      rated QoL was the dependent variable. Descriptive analyses were done to show
      group differences in QoL and logistic regression analyses to identify
      determinants of QoL. Advanced age, poor household economic status, and low social
      capital at individual and community levels were significant determinants of poor
      QoL among the elderly. This population-based study provided empirical evidence
      that social capital both at individual and community levels was directly
      associated with the QoL of elderly people in rural Bangladesh.

PMID- 16648395
TI  - Satisfaction with general practitioner treatment of depression among residents of
      aged care facilities.
AB  - OBJECTIVE: This article investigates consumer perspectives on the treatment for
      depression among older people in residential facilities. METHOD: Aged care
      residents who were aware of being treated for depression in the past 6 months (24
      women and 7 men, mean age = 83 years) participated in an interview that assessed
      their perspective on treatments. RESULTS: Although more than half of the
      participants in the sample reported overall satisfaction with the medical
      treatments received for depression, qualitative data provided indications of
      unsatisfactory service delivery, including perceptions of low treatment efficacy,
      short consultation times, the failure to assess affective symptomatology, and
      negative responses to residents' disclosure of symptoms. DISCUSSION: The findings
      are discussed in relation to previous research on consumer satisfaction with
      health services and issues that may be pertinent to the elderly depressed.
      Training for general practitioners providing treatment in aged care is indicated.

PMID- 16648396
TI  - Reports of abusive experiences during childhood and adult health ratings:
      personal control as a pathway?
AB  - OBJECTIVE: This study examines the relationship between reports of childhood
      abuse and self-rated health in adulthood, and the potential of personal control
      to serve as a mediator. METHOD: Regression models were estimated using data from
      the National Survey of Midlife Development in the United States (MIDUS). RESULTS:
      Reported emotional abuse was associated with lower personal control. In addition,
      women who reported emotional abuse by mother or both parents were more likely
      than women who were not abused to report lower self-rated health. The
      relationship between emotional abuse by both parents and self-rated health was
      mediated by personal control. DISCUSSION: The findings suggest that there are
      long-term health consequences of early childhood abuse. The effects of childhood
      abusive experiences, however, operate differently for men and women and are
      dependent on the outcome examined. Childhood abuse compromises personal control
      that, in turn, leads to lower health ratings.

PMID- 16648397
TI  - Worldwide involvement.

PMID- 16648399
TI  - Improving hospital systems for the care of women with major obstetric hemorrhage.
AB  - OBJECTIVE: When 2 maternal deaths due to hemorrhage occurred at New York Hospital
      Queens in 2000-2001, a multidisciplinary team implemented systemic change. Our
      objective was to improve outcomes of episodes of major obstetric hemorrhage.
      METHODS: We report outcomes before (2000-2001) and after (2002-2005) the
      introduction of a patient safety program aimed at improving the care of women
      with major obstetric hemorrhage. Process changes were instituted in late 2001 at
      the direction of a multidisciplinary patient safety team. A rapid response team
      was formulated using the cardiac arrest team as a model. Protocols for early
      diagnosis, assessment, and management of patients at high risk for major
      obstetric hemorrhage were developed and communicated to staff. RESULTS: There
      were significant increases in cesarean births (P < .001), repeat cesarean births
      (P = .002), and cases of major obstetric hemorrhage (P = .02) between the periods
      of 2000-2001 and 2002-2005. There was a significant improvement in mortality due
      to hemorrhage (P = .036), lowest pH (P = .004), and lowest temperature (P < .001)
      when comparing 2000-2001 with 2002-2005. There were no differences in measures of
      severity of obstetric hemorrhage between the 2 periods, including Acute
      Physiology and Chronic Health Evaluation II scores, occurrence of placenta
      accreta and estimated blood loss. CONCLUSION: Despite a significant increase in
      major obstetric hemorrhage cases, we found improved outcomes and fewer maternal
      deaths after implementing systemic approaches to improve patient safety.
      Attention to improving the hospital systems necessary for the care of women at
      risk for major obstetric hemorrhage is important in the effort to decrease
      maternal mortality from hemorrhage.

PMID- 16648400
TI  - Maternal and neonatal outcomes after attempted suicide.
AB  - OBJECTIVE: The purpose of this study was to describe identifiers and estimate
      maternal and neonatal outcomes in women who attempt suicide during pregnancy.
      METHODS: A linked Vital Statistics-Patient Discharge database of the State of
      California was used to identify cases of intentional injury during pregnancy. A
      retrospective analysis of maternal and neonatal outcomes in pregnant women who
      were admitted for attempted suicide is presented. RESULTS: There were 4,833,286
      deliveries in California from 1991 to 1999. Of those deliveries, 2,132 were
      complicated by attempted suicide during pregnancy (0.4 per 1,000 pregnancies).
      The control population was composed of patients who did not attempt suicide. The
      group of women that attempted suicide during pregnancy had increases in premature
      labor, cesarean delivery, and need for blood transfusion. Analysis of neonatal
      outcomes revealed increases in respiratory distress syndrome and low birth weight
      infants. A subanalysis, including women who delivered at the hospitalization for
      attempted suicide, demonstrated increased premature delivery, respiratory
      distress syndrome, and neonatal and infant death. CONCLUSION: Attempted suicide
      is associated with significantly higher rates of maternal and perinatal
      morbidity, and in some cases, perinatal mortality. The best identifier for women
      at risk for attempting suicide is substance abuse. Care provider identification
      and prevention are of key importance in preventing these outcomes.

PMID- 16648401
TI  - Influence of rest during pregnancy on birth weight in working women.
AB  - OBJECTIVE: Birth weight in Sweden has increased during the past decades. We
      investigated whether rest provided by the combination of time off from work and
      social benefits among working pregnant women contributed to the observed changes.
      METHOD: A total of 7,459 consecutively delivered women in 1978, 1986, 1992, and
      1997 at 2 delivery wards in southeastern Sweden were studied. RESULTS: Between
      1978 and 1997, the average birth weight among the children of the women studied
      increased from 3,484 to 3,566 grams (P < .001). The in-crease in weight was most
      evident among infants born to women who were employed during pregnancy. The use
      of social benefits and increased rest during pregnancy did not significantly
      influence birth weight (P = .107), even after adjustment for gestational length,
      parity, smoking, age, and occupation. CONCLUSION: The continuous increase in
      infants' birth weight among pregnant women in this study did not correlate with
      rest periods in the form of leave supported by social benefit programs. The
      effects of social benefit programs on pregnancy outcome may thus be overrated and
      merits further research.

PMID- 16648402
TI  - Cost-effectiveness analysis of liquid-based cytology and human papillomavirus
      testing in cervical cancer screening.
AB  - OBJECTIVE: To compare the outcomes of several cervix cancer screening strategies
      in a military population using a model that considers both direct and indirect
      costs of health care. METHODS: A Markov model of the natural history of cervical
      cancer was used to simulate an age-stratified cohort of 100,000 active duty women
      in the U.S. Army. Total costs and incremental cost-effectiveness ratios were
      estimated for different modalities of screening: liquid-based cytology with
      testing for human papillomavirus (HPV) irrespective of cytologic results compared
      with liquid-based cytology with HPV detection for cytologic results of atypical
      cells of undetermined significance (reflex HPV). The costs and outcomes of these
      screening methods were evaluated separately as well as in combination (liquid
      based cytology and reflex HPV before age 30 years and DNA and Pap test every 3
      years thereafter). Each of these screening methods was evaluated at 1-, 2-, and 3
      year intervals. RESULTS: A screening strategy of liquid-based cytology and reflex
      HPV every 2 or 3 years is the least costly strategy among active duty women
      irrespective of age, especially when accounting for time costs associated with
      screening, diagnosis, and treatment of cervix cancer. A strategy of liquid-based
      cytology and HPV testing irrespective of cytology results is the most effective
      strategy; however, it is also the most costly of the strategies tested, even when
      performed in patients older than 30 years of age. CONCLUSION: In the U.S. Army,
      cervix cancer screening performed with liquid-based cytology and reflex HPV
      testing of atypical squamous cells of undetermined significance performed every 2
      years is cost-effective, especially when indirect costs are considered.

PMID- 16648403
TI  - Predictors of low risk of persistent trophoblastic disease in molar pregnancies.
AB  - OBJECTIVE: To search for predictive factors for low risk of persistent
      trophoblastic disease in patients with molar pregnancies. METHODS: A total of 270
      consecutively collected, histologically confirmed hydatidiform moles were
      classified by ploidy using karyotyping and flow cytometry. The parental origin of
      the genome was determined by analysis of microsatellite polymorphisms. Data on
      clinical features and pathology reports were collected for each patient. RESULTS:
      The observed frequency of persistent trophoblastic disease in patients with
      triploid moles was 0 of 105, (95% confidence interval 0-2.8%), whereas 28 of 162
      patients with diploid molar pregnancies developed persistent trophoblastic
      disease (P < .001). Patients with a diploid mole and an initial hCG level lower
      than 49,000 units per liter did not develop persistent trophoblastic disease (P =
      .03). CONCLUSION: The risk of persistent trophoblastic disease after a triploid
      mole is very low. By combining the present data with data from published studies
      with valid ploidy assessment, the frequency of persistent trophoblastic disease
      in patients with triploid moles is 0 of 196 (95% confidence interval 0-1.5%). We
      suggest that the surveillance program for patients with triploid molar
      pregnancies is shortened. Initial hCG less than 49,000 units per liter is a
      possible predictor of low risk of persistent trophoblastic disease in women with
      diploid molar pregnancies, but this observation needs confirmation in larger
      studies.

PMID- 16648404
TI  - Methotrexate, bleomycin, and Etoposide in the treatment of gestational
      trophoblastic neoplasia.
AB  - OBJECTIVE: The combination of methotrexate (1 g/m(2) day 1), bleomycin (10 mg day
      3), and etoposide (100 mg/m(2) days 1-5) (MBE) has been used for disease relapse
      or as a second-line chemotherapy in the treatment of gestational trophoblastic
      neoplasia (GTN) resistant to multiple-agent chemotherapy. With the identification
      of ultra-high-risk GTN, MBE has also been used as first-line chemotherapy. The
      current study is to review the use of MBE in the treatment of GTN. METHODS:
      Patients who received MBE for GTN between 1985 and 2003 in Queen Mary Hospital
      were included in this study. Records were reviewed and data were analyzed.
      Outcomes including response rate, treatment complications, and survival were
      assessed. RESULTS: Methotrexate, bleomycin, and etoposide therapy was given as
      first line to 4 patients with ultra-high-risk GTN. Three responded to the
      treatment and remained disease free. Methotrexate, bleomycin, and etoposide were
      given as a second-line therapy to 8 patients who had drug resistance to the
      initial therapy. Seven responded, and 6 remained disease free at 5 years.
      Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8
      patients who relapsed 2-18 months after their initial therapy. Seven patients
      responded, and 4 remained disease-free at 5 years, 2 defaulted, and one died of
      carcinoma of the colon. Of the 20 patients who received MBE, 12 developed grade
      3/4 neutropenia, and 4 developed grade 3/4 thrombocytopenia. The overall response
      rate for MBE was 85%. CONCLUSION: Methotrexate, bleomycin, and etoposide should
      be considered as a second-line therapy in patients who have drug-resistant or
      recurrent GTN.

PMID- 16648405
TI  - Trends in the incidence of invasive and in situ vulvar carcinoma.
AB  - OBJECTIVE: To characterize the incidence of vulvar carcinoma in situ and vulvar
      cancer over time. METHODS: We used the Surveillance Epidemiology and End Results
      database to assess trends in the incidence of vulvar cancer over a 28-year period
      (1973 through 2000) and determined whether there had been a change in incidence
      over time. Information collected included patient characteristics, primary tumor
      site, tumor grade, and follow-up for vital status. We calculated the incidence
      rates by decade of age, used chi(2) tests to compare demographic characteristics,
      and tested for trends in incidence over time. RESULTS: A total of 13,176 in situ
      and invasive vulvar carcinomas were identified; 57% of the women were diagnosed
      with in situ, 44% with invasive disease. Vulvar carcinoma in situ increased 411%
      from 1973 to 2000. Invasive vulvar cancer increased 20% during the same period.
      The incidence rates for in situ and invasive vulvar carcinomas are distributed
      differently across the age groups. In situ carcinoma incidence increases until
      the age of 40-49 years and then decreases, whereas invasive vulvar cancer risk
      increases as a woman ages, increasing more quickly after 50 years of age.
      CONCLUSION: The incidence of in situ vulvar carcinoma is increasing. The
      incidence of invasive vulvar cancer is also increasing but at a much lower rate.

PMID- 16648406
TI  - Vulvar, vaginal, and perianal intraepithelial neoplasia in women with or at risk
      for human immunodeficiency virus.
AB  - OBJECTIVE: To compare the incidence of vulvar, vaginal, and perianal
      intraepithelial neoplasia among human immunodeficiency virus (HIV)-infected women
      with a group of well-matched high-risk HIV-uninfected controls. METHODS: A total
      of 192 HIV-infected and 88 uninfected women at high risk for HIV were followed up
      prospectively in Providence, Rhode Island during a 6-year period. Pap tests and
      cervicovaginal lavage for human papillomavirus detection and typing were
      performed at baseline and every 6 months thereafter. All women referred for
      colposcopy underwent a full colposcopic evaluation, including the vulvar,
      vaginal, and perianal regions. Unadjusted hazard ratios with 95% confidence
      intervals were calculated for development of vulvar, vaginal, and perianal
      intraepithelial neoplasia using univariable Cox proportional hazards models. An
      incidence analysis was performed by calculating Kaplan-Meier survival curves for
      development of intraepithelial neoplasia. RESULTS: At baseline, 3 (1.6%) of the
      192 HIV-infected women and none of the 88 HIV-uninfected women had vulvar,
      vaginal, and perianal intraepithelial neoplasia. During the study, 16 of 189
      (8.5%) HIV-infected women and 1 of 88 (1.1%) HIV-uninfected women developed
      vulvar, vaginal, and perianal intraepithelial neoplasia. The incidence of vulvar,
      vaginal, or anal intraepithelial neoplasia was 1.96 per 100 person years for the
      HIV-infected women and 0.26 per 100 person-years for the HIV-uninfected women (P
      = .03). CONCLUSION: Human immunodeficiency virus-infected women had more vulvar,
      vaginal, and perianal intraepithelial lesions compared with HIV-uninfected women.
      Furthermore, the incidence rates were higher than has been found in HIV-infected
      women in other similar cohorts.

PMID- 16648407
TI  - Comparison of labor progression between induced and noninduced multiparous women.
AB  - OBJECTIVE: The incidence of labor induction is rising rapidly in the United
      States. Among multiparas, labor is often followed with traditional labor curves
      derived from noninduced pregnancies. We sought to determine how labor progression
      of multiparous women who presented in spontaneous labor differed from those who
      were electively induced with and from those induced without preinduction cervical
      ripening. METHODS: We analyzed data on all low-risk multiparous women with an
      elective induction or spontaneous onset of labor between 37(+0) and 40(+6) weeks
      of gestation from January 2002 to March 2004 at a single institution. The median
      duration of labor by each centimeter of cervical dilatation and the risk of
      cesarean delivery were computed for 61 women with preinduction cervical ripening
      and oxytocin induction, 735 women with oxytocin induction, and 1,885 women with a
      spontaneous onset of labor. An intracervical Foley catheter was used to ripen the
      cervix. RESULTS: Those women who experienced electively induced labor without
      cervical ripening had a shorter active phase of labor than did those admitted in
      spontaneous labor (99 minutes in induced labor versus 161 minutes in spontaneous
      labor, P < .001). However, the cesarean delivery rate was elevated in the
      induction group (3.9% versus 2.3%, P < .05). Women who underwent preinduction
      cervical ripening also had a shorter active phase than those admitted in
      spontaneous labor (109 minutes versus 161 minutes, P = .01). CONCLUSION: The
      pattern of labor progression differs for women with an electively induced labor
      without cervical ripening compared with those who present with spontaneous onset
      of labor.

PMID- 16648408
TI  - Temporal trends of preterm birth subtypes and neonatal outcomes.
AB  - OBJECTIVE: To describe temporal trends of preterm birth subtypes, neonatal
      morbidity, and hospital neonatal mortality. METHODS: A database of 1.7 million
      births that occurred in 51 maternity hospitals in Latin America from 1985 to 2003
      was studied. Subgroups of preterm births were classified according to the
      presence or absence of maternal medical or obstetric complications, spontaneous
      labor, preterm labor after premature rupture of membranes, induction of labor, or
      elective cesarean. Outcomes studied, for different periods, were prevalence of
      small for gestational age, neonatal morbidity, and neonatal mortality. RESULTS:
      Spontaneous preterm labor without maternal complications was the most frequent
      subtype of preterm birth (60%), followed by premature rupture of membranes
      without maternal complications. Preterm births due to elective induction and
      delivery by elective cesarean increased markedly in the last 20 years, from 10%
      in 1985-1990 to 18.5% in recent years. Neonates born after spontaneous labor
      without maternal complications had the lowest mortality rate, but their large
      numbers made them responsible for one half of the preterm mortality. The
      induction followed by elective cesarean subgroups accounted for 13.4% of the
      preterm deaths between 1985 and 1990 and increased to 21.2% between 1996 and
      2003. CONCLUSION: Spontaneous labor in mothers without maternal complications is
      the most frequent cause of preterm births and is also the most important subgroup
      related to neonatal mortality. However, preterm births due to induction of labor
      or elective cesarean are increasing in Latin America and are becoming important
      contributors to neonatal mortality.

PMID- 16648409
TI  - Predicting pH at birth in absent or reversed end-diastolic velocity in the
      umbilical arteries.
AB  - OBJECTIVE: To investigate arterial and venous blood flow in fetuses with absent
      or reversed end-diastolic flow in the umbilical arteries and to correlate the
      Doppler results with umbilical artery blood pH at birth to predict the
      probability of acidosis at birth. METHODS: Ninety-one fetuses from singleton
      pregnancies without fetal malformations with a diagnosis of absent or reversed
      end-diastolic flow in the umbilical arteries were prospectively studied. On the
      day of delivery, Doppler velocimetry of the umbilical arteries, middle cerebral
      artery, and ductus venosus was performed and the results were correlated with
      umbilical artery pH at birth at the following cutoff levels: pH < 7.20, < 7.15, <
      7.10, and < 7.05. The association between fetal arterial and venous Doppler
      velocimetry and acidosis was then individually analyzed by the chi(2) and Fisher
      exact tests. The ability of these tests to predict the probability of acidosis at
      birth was estimated using a logistic regression model. RESULTS: There was a
      negative correlation between pH at birth and umbilical artery pulsatility index
      (r = -0.39; P < .001) and pulsatility index for veins in the ductus venosus (r = 
      0.63; P < .001). Assessment of the fetal arterial circulation (middle cerebral
      artery) showed no statistical correlation with pH at birth. Using logistic
      regression analysis, probability curves were constructed for pH values less than
      7.20 (odds ratio [OR] 8.03), less than 7.15 (OR 11.92), less than 7.10 (OR
      12.16), and less than 7.05 (OR 8.20). CONCLUSION: The pulsatility index for veins
      of the ductus venosus was related to pH at birth, demonstrating that the higher
      the ductus venosus pulsatility index for veins, the lower the pH at birth. Once
      the pulsatility index for veins in the ductus venosus is known, the probability
      of acidosis at birth can be estimated.

PMID- 16648410
TI  - Umbilical coiling index in normal and complicated pregnancies.
AB  - OBJECTIVE: To estimate the relation between undercoiling and overcoiling of the
      umbilical cord and adverse pregnancy outcome. METHODS: Umbilical cords and
      hospital records of 885 patients were studied in a cross-sectional study design.
      The umbilical coiling index was determined as the number of complete coils
      divided by the length of the cord in centimeters, blinded for pregnancy outcome.
      Obstetric history and pregnancy outcome of each patient were obtained from
      hospital records, blinded for the umbilical coiling index. Odds ratios and their
      95% confidence intervals were calculated to evaluate associations between
      undercoiling and overcoiling and adverse pregnancy outcome, using multiple
      logistic regression. RESULTS: Undercoiling (umbilical coiling index below the
      10th percentile, using references values from uncomplicated pregnancies) was
      associated with fetal death (odds ratio [OR] 3.35, 95% confidence interval [CI]
      1.48-7.63), spontaneous preterm delivery (OR 2.16, 95% CI 1.34-3.48), trisomies
      (OR 5.79, 95% CI 2.07-16.24), low Apgar score at 5 minutes (OR 3.14, 95% CI 1.47
      6.70), velamentous cord insertion (OR 3.00, 95% CI 1.16-7.76), single umbilical
      artery (OR 3.68, 95% CI 1.26-10.79), and dextral coiling (OR 1.80, 95% CI 1.02
      3.17). Overcoiling (umbilical coiling index above the 90th percentile) was
      associated with asphyxia (OR 4.16, 95% CI 1.30-13.36), umbilical arterial pH <
      7.05 (OR 2.91, 95% CI 1.05-8.09), small for gestational age infants (OR 2.10, 95%
      CI 1.01-4.36), trisomies (OR 9.26, 95% CI 2.84-30.2), single umbilical artery (OR
      8.25, 95% CI 2.60-26.12), and sinistral coiling (OR 4.30, 95% CI 1.52-12.2).
      CONCLUSION: Undercoiling and overcoiling of the umbilical cord are associated
      with increased risk for adverse perinatal outcome.

PMID- 16648411
TI  - Factors associated with increased charges for hysterectomy.
AB  - OBJECTIVE: To evaluate factors associated with increased hospital charges for
      hysterectomy with specific attention to differences based on surgical approach.
      METHODS: We performed a retrospective cohort study of 686 patients who underwent
      hysterectomy between January 1997 and September 1997 using medical chart review
      and hospital financial information. Demographic information, surgical approach
      (abdominal, vaginal, or laparoscopic), and surgical and postoperative factors
      were extracted from the medical record. Hospital charges were obtained from the
      hospital billing database. Relationships between charges and various clinical and
      demographic variables were examined using chi(2), Fisher exact test, t tests, or
      analysis of variance, where appropriate. Logistic regression was used to estimate
      odds ratios while controlling for important confounding variables. RESULTS: In
      our logistic regression model, blood loss greater than 1,000 mL (odds ratio [OR]
      11.8, 95% confidence interval [CI] 4.2-33.2) and operative time 105 minutes or
      more (OR 14.2, CI 5.8-34.5) were strongly associated with higher charges for
      hysterectomy. Other factors associated with higher charges included:
      postoperative fever (OR 2.2, CI 1.1-4.5), increasing length of hospitalization
      (OR 5.3, CI 3.7-7.7), the use of prophylactic antibiotics (OR 3.0, CI 1.3-6.6),
      and the laparoscopic surgical approach compared with vaginal hysterectomy (OR
      2.7, CI 1.0-7.0). CONCLUSION: Surgical factors such as operative time and blood
      loss were strongly associated with increased hospital charges for hysterectomy.

PMID- 16648412
TI  - Appearance of the levator ani muscle subdivisions in magnetic resonance images.
AB  - OBJECTIVE: Identify and describe the separate appearance of 5 levator ani muscle
      subdivisions seen in axial, coronal, and sagittal magnetic resonance imaging
      (MRI) scan planes. METHODS: Magnetic resonance scans of 80 nulliparous women with
      normal pelvic support were evaluated. Characteristic features of each
      Terminologia Anatomica-listed levator ani component were determined for each scan
      plane. Muscle component visibility was based on pre-established criteria in
      axial, coronal, and sagittal scan planes: 1) clear and consistently visible
      separation or 2) different origin or insertion. Visibility of each of the levator
      ani subdivisions in each scan plane was assessed in 25 nulliparous women.
      RESULTS: In the axial plane, the puborectal muscle can be seen lateral to the
      pubovisceral muscle and decussating dorsal to the rectum. The course of the
      puboperineal muscle near the perineal body is visualized in the axial plane. The
      coronal view is perpendicular to the fiber direction of the puborectal and
      pubovisceral muscles and shows them as "clusters" of muscle on either side of the
      vagina. The sagittal plane consistently demonstrates the puborectal muscle
      passing dorsal to the rectum to form a sling that can consistently be seen as a
      "bump." This plane is also parallel to the pubovisceral muscle fiber direction
      and shows the puboperineal muscle. CONCLUSION: The subdivisions of the levator
      ani muscle are visible in MRI scans, each with distinct morphology and
      characteristic features.

PMID- 16648413
TI  - Contraceptive counseling of diabetic women of reproductive age.
AB  - OBJECTIVE: To evaluate the impact of diabetes on provision of contraceptive
      counseling. METHODS: We compared counseling provided to diabetic and nondiabetic
      women on 40,304 visits made to U.S. ambulatory practices by nonpregnant women, 14
      44 years of age, included in the National Ambulatory Medical Care Survey and
      National Hospital Ambulatory Medical Care Survey, 1997-2000. Logistic regression,
      adjusting for age, race, ethnicity, insurance status, and provider
      characteristics was used to estimate the relationship between provision of
      contraceptive counseling and diabetes. RESULTS: Visits made by diabetic women of
      reproductive age were significantly less likely to include contraceptive
      counseling than visits made by nondiabetic women of reproductive age (odds ratio
      [OR] 0.42, 95% confidence interval [CI] 0.21-0.81). Visits made by diabetic women
      under 25 years of age were less likely to include contraceptive counseling than
      visits made by older diabetic women (OR 0.17, 95% CI 0.06-0.54). Overall, only 4%
      of visits made by diabetic women documented contraceptive counseling. When family
      planning was the primary reason for a visit (OR 34.4, 95% CI 20.8-56.9) or women
      visited a gynecologist (OR 24.3, 95% CI 16.7-35.2), women were significantly more
      likely to receive contraceptive counseling. However, diabetic women made only
      0.3% of all visits to gynecologists. CONCLUSION: Ambulatory physicians in the
      United States rarely provide contraceptive counseling to diabetic women. This may
      contribute to adverse birth outcomes for some diabetic mothers who conceive
      before optimal glucose control is obtained.

PMID- 16648414
TI  - Incidence and survival rates for female malignant germ cell tumors.
AB  - OBJECTIVE: To evaluate 30-year, population-based trends in incidence and survival
      rates for malignant germ cell tumors originating within the female genital tract.
      METHODS: Surveillance, Epidemiology, and End Results data were used to identify
      malignant germ cell tumors (1973-2002). Overall and 5-year incidence rates,
      estimated annual percentage change, and survival rates were calculated and
      compared by age at diagnosis, race, stage, and histology. RESULTS: Of 1,262
      cases, there were 414 (32.8%) dysgerminomas, 449 (35.6%) immature teratomas, 37
      (2.9%) mature teratomas with malignant degeneration, and 362 (28.7%) mixed germ
      cell tumors. The 30-year, age-adjusted incidence rate per 100,000 women-years was
      0.338, decreasing by 29.4% for dysgerminomas (P = .18) and by 31.5% for mixed
      germ cell tumors (P = .22). Other nonwhites had higher rates than whites and
      blacks, but dysgerminoma rates were higher in whites and other nonwhites than in
      blacks. Using the registries for expanded races, rates were higher for
      Asian/Pacific Islanders (P = .059) and Hispanics (P = .07). By age at diagnosis,
      15-19 year olds had the highest rates and the only significant change in rates
      (37.5% increase, P = .008). The 5-year relative survival was 83.9%. Survival
      rates improved significantly over calendar time and varied by histologic subtype,
      race, stage of disease, and age at diagnosis. CONCLUSION: Over the past 30 years,
      germ cell tumor incidence rates have declined in women and differ from rising
      trends reported for testicular tumors. Survival rates have improved but were
      lower for older women and for nondysgerminoma subtypes.

PMID- 16648415
TI  - Beyond race or ethnicity and socioeconomic status: predictors of prenatal testing
      for Down syndrome.
AB  - OBJECTIVE: To identify predictors of prenatal genetic testing decisions and
      explore whether racial or ethnic and socioeconomic differences are explained by
      knowledge, attitudes, and preferences. METHODS: This was a prospective cohort
      study of 827 English-, Spanish-, or Chinese-speaking pregnant women presenting
      for care by 20 weeks of gestation at 1 of 23 San Francisco Bay-area obstetrics
      clinics and practices. Our primary outcome measure for women aged less than 35
      years was any prenatal genetic testing use compared with none, and for women aged
      35 years or older, prenatal testing strategy (no testing, screening test first,
      straight to invasive diagnostic testing). Baseline questionnaires were completed
      before any prenatal test use; test use was assessed after 30 gestational weeks.
      RESULTS: Among women aged less than 35 years, no racial or ethnic differences in
      test use emerged. Multivariable analyses yielded three testing predictors:
      prenatal care site (P = .024), inclination to terminate pregnancy of a Down
      syndrome-affected fetus (odds ratio 2.94, P = .002) and belief that modern
      medicine interferes too much in pregnancy (odds ratio .85, P = .036). Among women
      aged 35 years or older, observed racial or ethnic and socioeconomic differences
      in testing strategy were mediated by faith and fatalism, value of testing
      information, and perceived miscarriage risk. Multivariable predictors of testing
      strategy included these 3 mediators (P = .035, P < .001, P = .037, respectively)
      and health care system distrust (P = .045). A total of 29.5% of screen-positive
      women declined amniocentesis; 6.6% of women screening negative underwent
      amniocentesis. CONCLUSION: Racial or ethnic and socioeconomic differences in
      prenatal testing strategy are mediated by risk perception and attitudes.
      Screening is not the best choice for many women. Optimal prenatal testing
      counseling requires clarification of risks and consideration of key attitudes and
      preferences regarding the possible sequence of events after testing decisions.

PMID- 16648416
TI  - History of miscarriage and increased incidence of fetal aneuploidy in subsequent
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      history of spontaneous abortion and aneuploidy in a subsequent pregnancy.
      METHODS: This was a retrospective cohort study of women who underwent fetal
      karyotype analysis with amniocentesis or chorionic villus sampling at a single
      prenatal diagnosis center. Information on spontaneous abortions, parity, maternal
      age, ethnicity, type of prenatal diagnosis, and karyotype was assessed.
      Univariable and multivariable analyses were conducted. RESULTS: A total of 46,939
      women were included in our analysis. Women with no prior spontaneous abortions
      had a 1.39% risk for any aneuploidy. In women with one prior spontaneous
      abortion, this risk increased to 1.67%; for women with 2 previous spontaneous
      abortions, the risk increased to 1.84%; and for those women who had had 3 or more
      prior spontaneous abortions, the risk increased further to 2.18% (P < .007). When
      controlling for maternal age, parity, ethnicity, and mode of prenatal diagnosis
      and compared with women with no prior spontaneous abortions, women with one prior
      spontaneous abortion (adjusted odds ratio [AOR] 1.21, 95% confidence interval
      [CI] 1.01-1.47) or 3 or more prior spontaneous abortions (AOR 1.51, 95% CI 1.02
      2.25) had a statistically significant increase in aneuploidy in a subsequent
      pregnancy. Women with 2 prior spontaneous abortions had an AOR of 1.26 for
      aneuploidy, but the 95% CI contained unity. CONCLUSION: An increased risk of
      karyotypic abnormality identified at the time of prenatal diagnosis is
      demonstrated in patients with an increasing number of spontaneous abortions. This
      study provides information regarding this risk among women presenting for
      prenatal diagnosis. According to our data, for a woman with an a priori risk of 1
      in 300 for Down syndrome, 3 prior spontaneous abortions would increase that risk
      by 47% to 1 in 204. These results should be confirmed in low-risk populations.

PMID- 16648417
TI  - Fractional excretion of angiogenic factors in women with severe preeclampsia.
AB  - OBJECTIVE: We estimated the fractional excretions of soluble fms-like tyrosine
      kinase 1 (sFlt-1), vascular endothelial growth factor, and placental growth
      factor of severely preeclamptic women at the time of disease clinical
      manifestation. METHODS: Levels of free sFlt-1, vascular endothelial growth
      factor, and placental growth factor were measured by immunoassay from time
      matched serum-urine samples from 64 women in the following groups: nonpregnant
      reproductive aged (n = 9), healthy pregnant controls (n = 13), mildly
      preeclamptic women (n = 15), and women with severe preeclampsia (n = 27). Urinary
      concentrations of angiogenic factors were normalized to creatinine and fractional
      excretions calculated. Correlations were estimated between fractional excretions
      of angiogenic factors, albuminuria, nonspecific proteinuria and urine protein-to
      creatinine ratio. RESULTS: Severely preeclamptic women had more than double
      urinary vascular endothelial growth factor (P = .01) and fractional excretion of
      vascular endothelial growth factor compared with mildly preeclamptic women (P =
      .007) or pregnant controls (P < .001). Serum, urine and fractional excretion
      levels of sFlt-1 were much higher among severely preeclamptic women compared with
      all the other pregnant groups (P < .001). Conversely, severely preeclamptic women
      had lower serum placental growth factor levels compared with healthy pregnant
      women (P < .05) and mildly preeclamptic groups (P < .05). Severely preeclamptic
      women had increased fractional excretions of placental growth factor, albumin,
      proteinuria, and random urine total protein/creatinine ratio. Among severely
      preeclamptic women there was no correlation between proteinuria and fractional
      excretion of vascular endothelial growth factor (r = 0.30, P = .127) or sFlt-1 (r
      = 0.35, P = .07). There was a significant correlation between fractional
      excretion for placental growth factor, random urine total protein/creatinine
      ratio (r = 0.60, P = .002), and nonspecific proteinuria (r = 0.50, P = .01).
      CONCLUSION: Severe preeclampsia is characterized by increased fractional
      excretion of angiogenic factors and especially of vascular endothelial growth
      factor, likely reflecting 2 separate phenomena that may have additive effects:
      "endogenous" renal production and glomerular "leakage."

PMID- 16648418
TI  - Effect of protease inhibitor therapy on glucose intolerance in pregnancy.
AB  - OBJECTIVE: To determine if protease inhibitor use was associated with increased
      glucose intolerance in our population of pregnant women infected with the human
      immunodeficiency virus (HIV). METHODS: Women who were infected with HIV from
      January 1, 1998, to January 8, 2004, and who had a 1-hour and 3-hour glucola test
      were identified. Medical records were reviewed to obtain demographic
      characteristics and obstetric and laboratory data. Drug regimens at the time of
      glucola testing were determined. Human immunodeficiency virus-infected women were
      then matched 1:3 to HIV-noninfected gravidas by race, age, and year of delivery.
      RESULTS: One hundred seventy-one HIV-infected women had glucola results
      available. Twelve percent had an abnormal 1-hour glucola result and 3% had an
      abnormal 3-hour result. This was similar to the HIV-noninfected population. Forty
      five percent of the HIV-infected cohort was on a protease inhibitor at the time
      of glucola testing. Protease inhibitor exposure had no effect on glucola test
      results. HIV infection itself also did not increase abnormal glucola test
      results. CONCLUSION: Glucose intolerance in this obstetric population was not
      associated with the diagnosis of HIV or with the use of protease inhibitors.
      Protease inhibitors should continue to be an option for the treatment of HIV in
      pregnancy.

PMID- 16648419
TI  - Antibiotic use in pregnancy and lactation: what is and is not known about
      teratogenic and toxic risks.
AB  - OBJECTIVE: Over ten million women are either pregnant or lactating in the United
      States at any time. The risks of medication use for these women are unique. In
      addition to normal physiologic changes that alter the pharmacokinetics of drugs,
      there is the concern of possible teratogenic and toxic effects on the developing
      fetus and newborn. This article reviews the risks and pharmacokinetic
      considerations for 11 broad-spectrum antibiotics that can be used to treat
      routine and life-threatening infections during pregnancy and lactation. DATA
      SOURCES: Information from the U.S. Food and Drug Administration (FDA) product
      labels, the Teratogen Information Service, REPROTOX, Shepard's Catalog of
      Teratogenic Agents, Clinical Pharmacology, and the peer-reviewed medical
      literature was reviewed concerning the use of 11 antibiotics in pregnant and
      lactating women. The PubMed search engine was used with the search terms
      "[antibiotic name] and pregnancy," "[antibiotic name] and lactation," and
      "[antibiotic name] and breastfeeding" from January 1940 to November 2005, as well
      as standard reference tracing. METHODS OF STUDY SELECTION: One hundred twenty
      four references had sufficient information concerning numbers of subjects,
      methods, and findings to be included. TABULATION, INTEGRATION, AND RESULTS: The
      teratogenic potential in humans ranged from "none" (penicillin G and VK) to
      "unlikely" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline,
      levofloxacin, and rifampin) to "undetermined" (clindamycin, gentamicin, and
      vancomycin). Assessments were based on "good data" (penicillin G and VK), "fair
      data" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin,
      and rifampin), "limited data" (clindamycin and gentamicin), and "very limited
      data" (vancomycin). Significant pharmacokinetic changes occurred during pregnancy
      for the penicillins, fluoroquinolones and gentamicin, indicating that dosage
      adjustments for these drugs may be necessary. With the exception of
      chloramphenicol, all of these antibiotics are considered compatible with
      breastfeeding. CONCLUSION: Health care professionals should consider the
      teratogenic and toxic risk profiles of antibiotics to assist in making
      prescribing decisions for pregnant and lactating women. These may become
      especially important if anti-infective countermeasures are required to protect
      the health, safety, and survival of individuals exposed to pathogenic
      bacteriologic agents that may occur from bioterrorist acts.

PMID- 16648420
TI  - Use of vaginally administered chlorhexidine during labor to improve pregnancy
      outcomes.
AB  - OBJECTIVE: Our objective was to determine the potential for chlorhexidine used as
      a vaginal and neonatal wash to reduce adverse outcomes of pregnancy, especially
      in developing countries. DATA SOURCES: We searched the English literature from
      January 1950 through October 2005 for all articles related to the use of
      chlorhexidine. METHODS OF STUDY SELECTION: Every article on chlorhexidine use in
      pregnancy and in the newborn period was reviewed in detail. The results of every
      study in which chlorhexidine was used as a vaginal treatment, with or without a
      neonatal wash, for all pregnancy outcomes except mother-to-child transmission of
      human immunodeficiency virus, are summarized in this review. TABULATION,
      INTEGRATION AND RESULTS: Chlorhexidine is a highly effective killer of most
      bacteria, has an excellent safety profile, rarely is associated with bacterial
      resistance, is easy to administer, and costs a few cents per application. When
      used as a vaginal or newborn disinfectant, it clearly reduces bacterial load,
      including transmission of Group B Streptococcus from the mother to the fetus.
      Nevertheless, in developed countries, chlorhexidine generally has not been shown
      to significantly reduce life-threatening maternal or neonatal infections.
      However, 2 large but not randomized studies, one in Malawi and the other in
      Egypt, suggest that important reductions in maternal and neonatal sepsis and
      neonatal mortality may be achievable with vaginal or neonatal chlorhexidine
      treatment. CONCLUSION: With 4 million neonates and about 700,000 pregnant or
      recently pregnant women-mostly in developing countries-dying each year, many from
      infections originating in the vagina, further study of this highly promising
      treatment is indicated.

PMID- 16648421
TI  - How my Ob-Gyn mentor influenced me.

PMID- 16648422
TI  - Refusals by pharmacists to dispense emergency contraception: a critique.
AB  - Over the past several months, numerous instances have been reported in the United
      States media of pharmacists refusing to fill prescriptions written for emergency
      postcoital contraceptives. These pharmacists have asserted a "professional right
      of conscience" not to participate in what they interpret as an immoral act. In
      this commentary, we examine this assertion and conclude that it is not
      justifiable, for the following reasons: 1) postcoital contraception does not
      interfere with an implanted pregnancy and, therefore, does not cause an abortion;
      2) because pharmacists do not control the therapeutic decision to prescribe
      medication but only exercise supervisory control over its dispensation, they do
      not possess the "professional right" to refuse to fill a legitimate prescription;
      3) even if one were to grant pharmacists the "professional right" not to dispense
      prescriptions based on their own personal values and opinions, pharmacists "at
      the counter" lack the fundamental prerequisites necessary for making clinically
      sound ethical decisions, that is, they do not have access to the patient's
      complete medical background or the patient's own ethical preferences, have not
      discussed relevant quality-of-life issues with the patient, and do not understand
      the context in which the patient's clinical problem is occurring. We conclude
      that a policy that allows pharmacists to dispense or not dispense medications to
      patients on the basis of their personal values and opinions is inimical to the
      public welfare and should not be permitted.

PMID- 16648423
TI  - Cervical cancer.
AB  - Worldwide, cervical cancer is the second most common malignancy in women and a
      major cause of morbidity and mortality. Until recently, the greatest strides in
      reducing cervical cancer mortality have occurred with the advent and
      implementation of screening programs. Many important advances have also taken
      place in the diagnosis and treatment of cervical cancer. This review article will
      highlight diagnostic and staging considerations with an emphasis on newer imaging
      modalities and how they might augment approved FIGO clinical staging. Management
      alternatives for patients with early-stage disease, locally advanced (stage IIB
      IVA) disease, and metastatic cervical cancer will be discussed. Whenever
      possible, these discussions will unfold through an overview of pertinent clinical
      trials and current controversies.

PMID- 16648424
TI  - Smoking habits, nicotine use, and congenital malformations.

PMID- 16648425
TI  - Smoking habits, nicotine use, and congenital malformations.

PMID- 16648426
TI  - Smoking habits, nicotine use, and congenital malformations.

PMID- 16648427
TI  - Smoking habits, nicotine use, and congenital malformations.

PMID- 16648428
TI  - Therapy for hypoxic ischemic encephalopathy: a cool idea and hypoxic ischemic
      encephalopathy and hypothermia: a critical look.

PMID- 16648429
TI  - Comparing three screening strategies for combining first- and second-trimester
      Down syndrome markers.

PMID- 16648431
TI  - How my Ob-gyn mentor influenced me.

PMID- 16648432
TI  - ACOG Practice Bulletin. Clinical management guidelines for obstetrician
      gynecologists, Number 72, May 2006: Vaginitis.
AB  - Vaginal symptoms are common in the general population and are one of the most
      frequent reasons for patient visits to obstetrician-gynecologists. Vaginitis may
      have important consequences in terms of discomfort and pain, days lost from
      school or work, and sexual functioning and self image. Vaginitis is associated
      with sexually transmitted diseases and other infections of the female genital
      tract, including human immunodeficiency virus (HIV), as well as adverse
      reproductive outcomes in pregnant and nonpregnant women. Treatment usually is
      directed to the specific cause of vaginal symptoms, which most commonly include
      bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. The purpose of
      this document is to provide information about the diagnosis and treatment of
      vaginitis.

PMID- 16648433
TI  - ACOG Committee Opinion. Number 332, May 2006 (replaces No. 203, July 1998):
      Hepatitis B and hepatitis C virus infections in obstetrician-gynecologists.
AB  - Hepatitis B and hepatitis C may be transmitted form patients to health care
      workers and from health care workers to patients. To reduce the risk, all
      obstetrician-gynecologists who provide clinical care should receive hepatitis B
      virus vaccine. Obstetrician-gynecologists who are hepatitis B surface antigen
      positive and e antigen positive should not perform exposure prone procedures
      until they have sought counsel from an expert review panel. Because the risk of
      hepatitis C virus transmission is lower than that of hepatitis B virus
      transmission, routine testing of health care workers is not recommended, and
      hepatitis C virus-positive health care workers are not required to restrict
      professional activities.

PMID- 16648434
TI  - ACOG Committee Opinion. Number 333, May 2006 (replaces No. 174, July 1996): The
      Apgar score.
AB  - The Apgar score provides a convenient shorthand for reporting the status of the
      newborn infant and the response to resuscitation. The Apgar score has been used
      inappropriately to predict specific neurologic outcome in the term infant. There
      are no consistent data on the significance of the Apgar score in preterm infants.
      The Apgar score has limitations, and it is inappropriate to use it alone to
      establish the diagnosis of asphyxia. An Apgar score assigned during resuscitation
      is not equivalent to a score assigned to a spontaneously breathing infant. An
      expanded Apgar score reporting form will account for concurrent resuscitative
      interventions and provide information to improve systems of perinatal and
      neonatal care.

PMID- 16648435
TI  - ACOG Committee Opinion. Number 334, May 2006 (replaces No. 186, September 1997):
      Role of the obstetrician-gynecologist in the screening and diagnosis of breast
      masses.
AB  - Obstetrician-gynecologists are in a favorable position to diagnose breast disease
      in their patients. Obstetrician-gynecologists are more likely to encounter a
      patient with breast cancer than a patient with any gynecologic cancer. The
      American College of Obstetricians and gynecologists (ACOG) has adopted the goals
      of assisting in educating obstetrician-gynecologists in the diagnosis and
      treatment of breast cancer and in reducing mortality from breast cancer. To help
      meet these goals, ACOG has developed recommendations for the early diagnosis of
      breast disease.

PMID- 16648436
TI  - ACOG Committee Opinion. Number 335, May 2006: The initial reproductive health
      visit.
AB  - The American College of Obstetrician and Gynecologists (ACOG) recommends the
      first visit to the obstetrician-gynecologist take place between the ages of 13
      and 15 years. This visits will provide health guidance, screening, and preventive
      health care services and provide an excellent opportunity for the obstetrician
      gynecologist to start a physician-patient relationship. This visit generally does
      not include an internal pelvic examination.

PMID- 16648438
TI  - Comparison of the effects of fan-assisted and natural ventilation of vehicles on
      the welfare of pigs being transported to slaughter.
AB  - A total of 417 pigs with an estimated average liveweight of 91 kg were
      transported to slaughter in three journeys, carried out in late June, each
      consisting of a three-hour drive followed by a one-hour holding period at the
      slaughter plant before they were unloaded. The pigs were accommodated on the
      lower two decks of a three-deck articulated lorry, each deck having five equal
      sized pens; half were kept in naturally ventilated pens and half in pens with fan
      assisted ventilation. The pigs' body temperature was recorded as the temperature
      of the blood lost at exsanguination, and as the temperature of the inner surface
      of the ear measured by thermal imaging. The pigs carried on the upper deck were
      hotter than those carried on the lower deck, and the pigs carried at the front of
      the vehicle were hotter than those at the back. There were small differences
      between the temperatures of the pigs in the different pens, but overall the
      temperatures of the pigs kept in pens with fan-assisted ventilation were no lower
      than those of the pigs kept in pens with natural ventilation. The higher
      temperature of the pigs transported in the front of the vehicle was associated
      with significantly higher serum concentrations of cortisol and activities of
      creatine kinase, and a tendency to higher albumin concentrations and osmolality,
      suggesting that they may have been exposed to more physical and psychological
      stress, and were possibly slightly more dehydrated, than the pigs in the rearmost
      pens. The type of ventilation had no effect on the blood composition of the pigs.

PMID- 16648439
TI  - Clinical findings and treatment of 94 cattle presumptively diagnosed with
      listeriosis.
AB  - The clinical findings and treatment of 94 cattle with listeriosis are described.
      The general behaviour and condition of the animals were mostly moderately to
      severely disturbed. A common abnormality in posture was an exaggerated forward or
      sideward stance, and 11 of the animals were recumbent. More than half of the
      animals were ataxic and 22 circled. The most frequent cranial neurological signs
      observed were facial nerve paralysis, salivation, strabismus, reduced or absent
      pupillary light reflex, reduced or absent tongue movement and head tilt. The
      haematological and biochemical findings did not contribute to the diagnosis of
      listeriosis, but they were useful indicators of dehydration and the acid-base
      status of the animal. Forty-four of 57 of the animals had high leucocyte counts
      in the cerebrospinal fluid (CSF), mostly mononuclear cells. Eighty-seven of the
      animals were treated with various antibiotics (penicillin G, oxytetracycline,
      amoxicillin, and amoxicillin and gentamicin combined), but there was no
      significant difference in the success rate of the different treatments. Only two
      of the nine recumbent animals that were treated survived. Univariable analysis
      suggested that animals that were recumbent, excited, with an absent or weak
      menace reflex, nystagmus, high numbers of leucocytes in the CSF, high serum
      concentrations of urea and calcium and high serum activities of aspartate
      aminotransferase and creatine kinase, and an acid-base deficit, had a smaller
      chance of surviving. When a logistic regression model was constructed, only
      recumbency, excitement and a weak or absent menace reflex remained significant
      factors affecting the likelihood of survival.

PMID- 16648440
TI  - Multisite integumentary squamous cell carcinoma in an African grey parrot
      (Psittacus erithacus erithacus).
AB  - A 22-year-old male African grey parrot (Psittacus erithacus erithacus) had had
      episodes of chronic feather picking and self-mutilation for 10 years; it had a 5
      cm diameter right axillary wound and a 2 cm left dorsal patagial wound. Initial
      treatment with azithromycin and wound management was unsuccessful. Biopsies of
      both masses indicated squamous cell carcinoma. The left patagial tumour was
      removed completely by electrocautery. Cisplatin was administered weekly into
      multiple sites on the right axillary tumour and it initially appeared to regress;
      however, the bird's condition deteriorated after a month of treatment, and it was
      euthanased. The tumour was confirmed postmortem to be squamous cell carcinoma,
      which had invaded local tissues. The aetiology of the carcinoma may have been
      secondary to chronic focal trauma.

PMID- 16648441
TI  - Anthelmintic use and resistance on thoroughbred training yards in the UK.

PMID- 16648442
TI  - Atresia coli in an alpaca cria.

PMID- 16648443
TI  - Diskospondylitis and umbilical abscessation in a calf.

PMID- 16648444
TI  - Mortality caused by Clostridium novyi in outdoor sows in Slovakia.

PMID- 16648446
TI  - Postmortem identification of swans.

PMID- 16648447
TI  - Badgers, TB and modern farming practice.

PMID- 16648449
TI  - Cross-modal associations between odors and colors.
AB  - In the present study, we investigated the nature of any cross-modal associations
      between colors and odors. In Experiment 1, we show that participants consistently
      match certain odors to specific colors when asked to explicitly select from among
      different colors the one that best matched a given odor. In Experiment 2, we
      investigated the robustness of these cross-modal associations using a cross-modal
      variant of the implicit association test (IAT). Participants made speeded
      discrimination responses to a random sequence of odors (strawberry vs. spearmint)
      and color patches (pink vs. turquoise). On the basis of the results of Experiment
      1, the assignment of these targets onto the two response keys was manipulated in
      order to generate compatible (e.g., responding to the pink color and to the
      strawberry odor with the same response key) and incompatible (e.g., responding to
      the pink color and to the spearmint odor with the same response key) blocks of
      trials. The results showed that participants responded more rapidly and
      accurately to odor-color pairings having a stronger association than to those
      having a weaker (or no) association. These results suggest that odor-color
      associations can be both systematic and robust. The paradigm developed here
      provides a novel cross-modal extension of the IAT to probe the nature of color
      odor associations.

PMID- 16648450
TI  - Female snake sex pheromone induces membrane responses in vomeronasal sensory
      neurons of male snakes.
AB  - The vomeronasal organ (VNO) is important for activating accessory olfactory
      pathways that are involved in sexually dimorphic mating behavior. The VNO of male
      garter snakes is critically important for detection of, and response to, female
      sex pheromones. In the present study, under voltage-clamp conditions, male snake
      VNO neurons were stimulated with female sexual attractiveness pheromone. Thirty
      nine of 139 neurons exhibited inward current responses (reversal potential: -10.6
      +/- 2.8 mV). The amplitude of the inward current was dose dependent, and the
      relationship could be fitted by the Hill equation. Under current-clamp
      conditions, application of pheromone produced membrane depolarizing responses and
      increases in firing frequency. These results suggest that the female pheromone
      directly affects male snake VNO neurons and results in opening of ion channels,
      thereby converting the pheromone signal to an electrical signal. The response to
      female pheromone is sexually dimorphic, that is, the pheromone does not evoke
      responses in VNO neurons of female snakes. An associated finding of the present
      study is that the female sex pheromone, which is insoluble in aqueous solutions,
      became soluble in the presence of Harderian gland homogenate.

PMID- 16648451
TI  - High-frequency activity in human visual cortex is modulated by visual motion
      strength.
AB  - A central goal in systems neuroscience is to understand how the brain encodes the
      intensity of sensory features. We used whole-head magnetoencephalography to
      investigate whether frequency-specific neuronal activity in the human visual
      cortex is systematically modulated by the intensity of an elementary sensory
      feature such as visual motion. Visual stimulation induced a tonic increase of
      neuronal activity at frequencies above 50 Hz. In order to define a functional
      frequency band of neuronal activity, we parametrically investigated which
      frequency band displays the strongest monotonic increase of responses with
      strength of visual motion. Consistently in all investigated subjects, this
      analysis resulted in a functional frequency band in the high gamma range from
      about 60 to 100 Hz in which activity reliably increased with visual motion
      strength. Using distributed source reconstruction, we found that this increase of
      high-frequency neuronal activity originates from several extrastriate cortical
      regions specialized in motion processing. We conclude that high-frequency
      activity in the human visual motion pathway may be relevant for encoding the
      intensity of visual motion signals.

PMID- 16648452
TI  - Attention to form or surface properties modulates different regions of human
      occipitotemporal cortex.
AB  - We carried out 2 functional magnetic resonance imaging experiments to investigate
      the cortical mechanisms underlying the contribution of form and surface
      properties to object recognition. In experiment 1, participants performed same
      different judgments in separate blocks of trials on pairs of unfamiliar
      "nonsense" objects on the basis of their form, surface properties (i.e., both
      color and texture), or orientation. Attention to form activated the lateral
      occipital (LO) area, whereas attention to surface properties activated the
      collateral sulcus (CoS) and the inferior occipital gyrus (IOG). In experiment 2,
      participants were required to make same-different judgments on the basis of
      texture, color, or form. Again attention to form activated area LO, whereas
      attention to texture activated regions in the IOG and the CoS, as well as regions
      in the lingual sulcus and the inferior temporal sulcus. Within these last 4
      regions, activation associated with texture was higher than activation associated
      with color. No color-specific cortical areas were identified in these regions,
      although parts of V1 and the cuneus yielded higher activation for color as
      opposed to texture. These results suggest that there are separate form and
      surface-property pathways in extrastriate cortex. The extraction of information
      about an object's color seems to occur relatively early in visual analysis as
      compared with the extraction of surface texture, perhaps because the latter
      requires more complex computations.

PMID- 16648454
TI  - The timing of perceptual decisions for ambiguous face stimuli in the human
      ventral visual cortex.
AB  - When observers must discriminate a weak sensory signal in noise, early sensory
      areas seem to reflect the instantaneous strength of the sensory signal. In
      contrast, high-level parietal and prefrontal areas appear to integrate these
      signals over time with activity peaking at the time of the observer's decision.
      Here, we used functional magnetic resonance imaging to investigate how the brain
      forms perceptual decisions about complex visual forms in a challenging task,
      requiring the discrimination of ambiguous 2-tone Mooney faces and visually
      similar nonface images. Face-selective areas in the ventral visual cortex showed
      greater activity when subjects reported perceiving a face as compared with a
      nonface, even on error trials. More important, activity was closely related to
      the time of the subject's decision for face judgments, even on individual trials,
      and resembled the time course of activity in motor cortex corresponding to the
      subject's behavioral report. These results indicate that perceptual decisions
      about ambiguous face-like stimuli are reflected early in the sensorimotor
      pathway, in face-selective regions of the ventral visual cortex. Activity in
      these areas may represent a potential rate-limiting step in the pathway from
      sensation to action when subjects must reach a decision about ambiguous face-like
      stimuli.

PMID- 16648453
TI  - Quantitative analysis and subcellular distribution of mRNA and protein expression
      of the hyperpolarization-activated cyclic nucleotide-gated channels throughout
      development in rat hippocampus.
AB  - The properties of the hyperpolarization-activated current (I(h)) and its roles in
      hippocampal network function evolve radically during development. Because I(h) is
      conducted by the hyperpolarization-activated cyclic nucleotide-gated (HCN) cation
      channels, we tested the hypothesis that understanding the quantitative
      developmental profiles of HCN1, HCN2, and HCN4 expression, and the isoform- and
      age-specific progression of their subcellular distribution, should shed light on
      the established modifications of the properties of I(h) throughout development.
      Combined quantitative in situ hybridization, regional western blots, and high
      resolution, dual-label immunocytochemistry revealed striking and novel
      information about the expression and distribution of the HCN channel isoforms in
      the developing hippocampal formation. In cornus ammon 1 (CA) pyramidal cell
      layer, a robust increase of HCN1 mRNA and protein expression occurred with age,
      with reciprocal reduction of HCN4 and relatively stable HCN2 levels. These
      distinct expression patterns raised the contribution of HCN1 to the total HCN
      channel pool from 33% to 65% consonant with acceleration and reduced cyclic
      adenosine mono phosphate (cAMP) sensitivity of I(h) in this region with age. In
      CA3, strong expression of HCN1 already neonatally supports the recently
      established role of this conductance in neonatal, age-specific, hippocampal
      oscillations (giant depolarizing potentials). Notably, HCN1 channels were present
      and probably transported to dendritic compartments already on postnatal day (P)
      2, whereas HCN2 channel protein was not evident in dendrites for the first 2
      weeks of life. HCN2 mRNA and protein expression remained fairly constant
      subsequent to the first week of life in all hippocampal subfields examined,
      whereas HCN4 mRNA and protein expression declined after maximal neonatal
      expression, so that the contribution of this isoform to the total HCN channel
      pool dropped from 43% (CA1) and 34% (CA3) on P11 to 8% (CA1) and 19% (CA3) on
      P90. Interneuronal expression of all HCN channel isoforms in stratum pyramidale
      was robust in parvalbumin-but not in cholecystokinin-expressing populations and
      with a subunit-specific subcellular distribution. Taken together, these data
      suggest that early in life, HCN4 may contribute significantly to the functions of
      I(h) in specific hippocampal regions. In addition, these evolving, differential
      quantitative, and subcellular expression patterns of the HCN channel isoforms
      support age-specific properties and functions of I(h) within the developing
      hippocampal formation.

PMID- 16648455
TI  - Intracortically distributed neurovascular coupling relationships within and
      between human somatosensory cortices.
AB  - The coupling of neuronal cellular activity to its blood supply is of critical
      importance to the physiology of the human brain and has been under discussion for
      more than a century. Linearity in this relationship has been demonstrated in some
      animal studies, but evidence is lacking in humans. In this study, we compared
      scalp evoked potentials and the functional magnetic resonance imaging (fMRI)
      blood oxygen level-dependent (BOLD) signal from healthy human volunteers with
      changes in the intensity of a somatosensory stimulus. By weighting the fMRI
      images according to the evoked potential amplitude at corresponding intensities,
      we tested for positive and negative covariation between these 2 data sets and the
      extent to which these were linear. Hemodynamic changes in primary somatosensory
      cortex covaried positively with neuronal activity in a predominantly linear
      manner, with a small quadratic contribution. Simultaneously, other cortical areas
      corresponding to the nonstimulated limbs were found to covary negatively and
      linearly in the hemispheres ipsilateral and contralateral to the stimulus. These
      concurrent and bilateral cortical dynamics, as well as the intraregional features
      of this neurovascular coupling, are both more complex than had been considered to
      date, with considerable implications.

PMID- 16648456
TI  - Modulation of NMDA receptor current in layer V pyramidal neurons of the rat
      prefrontal cortex by P2Y receptor activation.
AB  - Current responses to N-methyl-D-aspartate (NMDA) in layer V pyramidal neurons of
      the rat prefrontal cortex were potentiated by the P2 receptor agonists adenosine
      5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP). The failure of these
      nucleotides to induce inward current on fast local superfusion suggested the
      activation of P2Y rather than P2X receptors. The potentiation by ATP persisted in
      a Ca(2+)-free superfusion medium but was abolished by 1,2-bis(2-amino-5
      fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester,
      cyclopiazonic acid, 7-nitroindazole, fluoroacetic acid, bafilomycin, and tetanus
      toxin, indicating that an astrocytic signaling molecule may participate. Because
      the metabotropic glutamate receptor (mGluR) agonists (1S,3R)-1-aminocyclopentane
      1,3-dicarboxylic acid (ACPD) (group I/II) and (RS)-3,5-dihydroxyphenylglycine
      (group I) both imitated the effect of ATP and the group I mGluR antagonist 1
      aminoindan-1,5-dicarboxylic acid or a combination of selective mGluR(1) (7
      (hydroxyimino)-cyclopropa[b]chromen-1a-carboxylate) and mGluR(5) (2-methyl-6
      (phenylethynyl)pyridine) antagonists abolished the facilitation by ATP, it was
      concluded that the signaling molecule may be glutamate. Pharmacological tools
      known to interfere with the transduction cascade of type I mGluRs (guanosine 5'-O
      (3-thiodiphosphate), U-73122, xestospongin C, 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid, calmodulin kinase II [CAMKII] inhibitor peptide)
      depressed the actions of both ATP and ACPD. Characterization of the P2Y receptor
      by agonists (ATP and UTP), antagonists (suramin and pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonic acid), and knockout mice (P2Y(2)(-/-)) suggested that
      the nucleotides act at the P2Y(4) subtype. In conclusion, we propose that
      exogenous and probably also endogenous ATP release vesicular glutamate from
      astrocytes by P2Y(4) receptor activation. This glutamate then stimulates type I
      mGluRs of layer V pyramidal neurons and via the G(q)/phospholipase C/inositol
      1,4,5-trisphosphate/Ca(2+)/CAMKII transduction pathway facilitates NMDA receptor
      currents.

PMID- 16648457
TI  - Neural processes underlying memory attribution on a reality-monitoring task.
AB  - A relatively common form of memory distortion arises when individuals must
      discriminate items they have seen from those they have imagined (reality
      monitoring). The present fMRI investigation (at 1.5 T) focused on the processes
      that relate to memory assignment regardless of accuracy (e.g. that correspond
      with the belief that an item was presented as a picture, regardless of whether
      that belief is correct). Prior to the scan, participants (n = 16) viewed concrete
      nouns and formed mental images of the object named. Half of the names were
      followed by the object's photo. During the scan, participants saw the object
      names and indicated whether the corresponding photo had been studied. Activity in
      visual-processing regions (including the precuneus and fusiform gyrus)
      corresponded with the attribution of an item to a pictorial presentation. In
      contrast, activity in regions thought to be important for self-referential
      processing (including the ventromedial prefrontal cortex and posterior cingulate
      gyrus) was associated with attribution to a nonpresented source. These neural
      findings converge with behavioral evidence indicating that individuals use the
      amount of different types of information retrieved (e.g. perceptual detail,
      information about cognitive operations) to determine whether an item was imagined
      or perceived.

PMID- 16648458
TI  - National survey of accommodations and alternate assessments for students who are
      deaf or hard of hearing in the United States.
AB  - This paper reports the results of the National Survey of Accommodations and
      Alternate Assessments for Students who are Deaf or Hard of Hearing in the United
      States (National Survey). This study focused on the use of accommodations and
      alternate assessments in statewide assessments used with students who are deaf or
      hard of hearing. A total of 258 participants responded to the survey, including
      32 representing schools for the deaf, 168 from districtwide/school programs, and
      58 from mainstreamed settings. These schools and programs served a total of
      nearly 12,000 students who are deaf or hard of hearing nationwide. The most
      prevalent accommodations used in 2003-2004 statewide standardized assessments in
      mathematics and reading were extended time, an interpreter for directions, and a
      separate room for test administration. Read aloud and signed question-response
      accommodations were often prevalent, used more often for mathematics than in
      reading assessments. Participants from mainstreamed settings reported a more
      frequent use of accommodations than those in schools for the deaf or
      districtwide/school programs. In contrast, schools for the deaf were most likely
      to have students participate in alternate assessments. The top three alternate
      assessment formats used across all settings were out-of-level testing, work
      samples, and portfolios. Using the National Survey results as a starting point,
      future research will need to investigate the validity of accommodations used with
      students who are deaf or hard of hearing. In the context of the No Child Left
      Behind Act of 2001 accountability policies, the accommodations and alternate
      assessment formats used with students who are deaf or hard of hearing may result
      in restrictions in how scores are integrated into state accountability
      frameworks.

PMID- 16648462
TI  - SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during
      mitosis.
AB  - The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+
      dependent protein deacetylases involved in caloric restriction-dependent life
      span extension. We found that SirT2 and its yeast counterpart Hst2 have a strong
      preference for histone H4K16Ac in their deacetylation activity in vitro and in
      vivo. We have pinpointed the decrease in global levels of H4K16Ac during the
      mammalian cell cycle to the G2/M transition that coincides with SirT2
      localization on chromatin. Mouse embryonic fibroblasts (MEFs) deficient for SirT2
      show higher levels of H4K16Ac in mitosis, in contrast to the normal levels
      exhibited by SirT1-deficient MEFs. The enzymatic conversion of H4K16Ac to its
      deacetylated form may be pivotal to the formation of condensed chromatin. Thus,
      SirT2 is a major contributor to this enzymatic conversion at the time in the
      cell's life cycle when condensed chromatin must be generated anew.

PMID- 16648463
TI  - Promoter mutations of an essential gene for pollen development result in disease
      resistance in rice.
AB  - Disease resistance and sexual reproductive development are generally considered
      as separate biological processes, regulated by different sets of genes. Here we
      show that xa13, a recessive allele conferring disease resistance against
      bacterial blight, one of the most devastating rice diseases worldwide, plays a
      key role in both disease resistance and pollen development. The dominant allele,
      Xa13, is required for both bacterial growth and pollen development. Promoter
      mutations in Xa13 cause down-regulation of expression during host-pathogen
      interaction, resulting in the fully recessive xa13 that confers race-specific
      resistance. The recessive xa13 allele represents a new type of plant disease
      resistance.

PMID- 16648464
TI  - Erasure of histone acetylation by Arabidopsis HDA6 mediates large-scale gene
      silencing in nucleolar dominance.
AB  - Nucleolar dominance describes the silencing of one parental set of ribosomal RNA
      (rRNA) genes in a genetic hybrid, an epigenetic phenomenon that occurs on a scale
      second only to X-chromosome inactivation in mammals. An RNA interference (RNAi)
      knockdown screen revealed that the predicted Arabidopsis histone deacetylase,
      HDA6, is required for rRNA gene silencing in nucleolar dominance. In vivo,
      derepression of silenced rRNA genes upon knockdown of HDA6 is accompanied by
      nucleolus organizer region (NOR) decondensation, loss of promoter cytosine
      methylation, and replacement of histone H3 Lys 9 (H3K9) dimethylation with H3K4
      trimethylation, H3K9 acetylation, H3K14 acetylation, and histone H4 tetra
      acetylation. Consistent with these in vivo results, purified HDA6 deacetylates
      lysines modified by histone acetyltransferases whose substrates include H3K14,
      H4K5, and H4K12. HDA6 localizes, in part, to the nucleolus, supporting a model
      whereby HDA6 erases histone acetylation as a key step in an epigenetic switch
      mechanism that silences rRNA genes through concerted histone and DNA
      modifications.

PMID- 16648465
TI  - Ndj1, a telomere-associated protein, promotes meiotic recombination in budding
      yeast.
AB  - Dynamic telomere repositioning is a prominent feature of meiosis. Deletion of a
      telomere-associated protein, Ndj1, results in the failure of both attachment and
      clustering of telomeres at the nuclear envelope and delays several landmarks of
      meiosis I, such as pairing, synaptonemal complex formation, and timing of the
      meiosis I division. We explored the role of Ndj1 in meiotic recombination, which
      occurs through the formation and repair of programmed double-strand breaks. The
      ndj1delta mutation allows for the formation of the first detectable strand
      invasion intermediate (i.e., single-end invasion) with wild-type kinetics;
      however, it confers a delay in the formation of the double-Holliday junction
      intermediate and both crossover and noncrossover products. These results
      challenge the widely held notion that clustering of telomeres in meiosis promotes
      the ability of homologous chromosomes to find one another in budding
      Saccharomyces cerevisiae. We propose that an Ndj1-dependent function is critical
      for stabilizing analogous strand invasion intermediates that exist in two
      separate branches of the bifurcated pathway, leading to either noncrossover or
      crossover formation. These findings provide a link between telomere dynamics and
      a distinct mechanistic step of meiotic recombination that follows the homology
      search.

PMID- 16648466
TI  - Tethering KSRP, a decay-promoting AU-rich element-binding protein, to mRNAs
      elicits mRNA decay.
AB  - Inherently unstable mRNAs contain AU-rich elements (AREs) in their 3'
      untranslated regions that act as mRNA stability determinants by interacting with
      ARE-binding proteins (ARE-BPs). We have destabilized two mRNAs by fusing sequence
      specific RNA-binding proteins to KSRP, a decay-promoting ARE-BP, in a tethering
      assay. These results support a model that KSRP recruits mRNA decay
      machinery/factors to elicit decay. The ability of tethered KSRP to elicit mRNA
      decay depends on functions of known mRNA decay enzymes. By targeting the Rev
      response element of human immunodeficiency virus type 1 by using Rev-KSRP fusion
      protein, we degraded viral mRNA, resulting in a dramatic reduction of viral
      replication. These results provide a foundation for the development of novel
      therapeutic strategies to inhibit specific gene expression in patients with
      acquired or hereditary diseases.

PMID- 16648467
TI  - Mapping of DNA replication origins to noncoding genes of the X-inactivation
      center.
AB  - In mammals, few DNA replication origins have been identified. Although there
      appears to be an association between origins and epigenetic regulation, their
      underlying link to monoallelic gene expression remains unclear. Here, we identify
      novel origins of DNA replication (ORIs) within the X-inactivation center (Xic).
      We analyze 86 kb of the Xic using an unbiased approach and find an unexpectedly
      large number of functional ORIs. Although there has been a tight correlation
      between ORIs and CpG islands, we find that ORIs are not restricted to CpG islands
      and there is no dependence on transcriptional activity. Interestingly, these ORIs
      colocalize to important genetic elements or genes involved in X-chromosome
      inactivation. One prominent ORI maps to the imprinting center and to a domain
      within Tsix known to be required for X-chromosome counting and choice. Location
      and/or activity of ORIs appear to be modulated by removal of specific Xic
      elements. These data provide a foundation for testing potential relationships
      between DNA replication and epigenetic regulation in future studies.

PMID- 16648468
TI  - Nuclear recycling of the pre-60S ribosomal subunit-associated factor Arx1 depends
      on Rei1 in Saccharomyces cerevisiae.
AB  - Arx1 and Rei1 are found on late pre-60S ribosomal particles containing the export
      adaptor Nmd3. Arx1 is related to methionine aminopeptidases (MetAPs), and Rei1 is
      a C2H2 zinc finger protein whose function in ribosome biogenesis has not been
      previously characterized. Arx1 and Rei1 localized predominately to the nucleus
      and cytoplasm, respectively, but could be coimmunoprecipitated, suggesting that
      they are transiently in the same 60S complex. arx1delta mutants showed a modest
      accumulation of 60S subunits in the nucleus, suggesting that Arx1 enhances 60S
      export. Deletion of REI1 led to cold sensitivity and redistribution of Arx1 to
      the cytoplasm, where it remained bound to free 60S subunits. However, deletion of
      ARX1 or the fusion of enhanced GFP (eGFP) to Rpl25 suppressed the cold
      sensitivity of an rei1delta mutant. The presence of eGFP on Rpl25 or its
      neighboring protein Rpl35 reduced the binding of Arx1 to 60S subunits, suggesting
      that Arx1 binds to 60S subunits in the vicinity of the exit tunnel. Mutations in
      Arx1 that disrupted its binding to 60S also suppressed an rei1delta mutant and
      restored the normal nuclear localization of Arx1. These results indicate that the
      cold sensitivity of rei1delta cells is due to the persistence of Arx1 on 60S
      subunits in the cytoplasm. Furthermore, these results suggest that Rei1 is needed
      for release of Arx1 from nascent 60S subunits after export to the cytoplasm but
      not for the subsequent nuclear import of Arx1.

PMID- 16648469
TI  - Nickel ions increase histone H3 lysine 9 dimethylation and induce transgene
      silencing.
AB  - We have previously reported that carcinogenic nickel compounds decreased global
      histone H4 acetylation and silenced the gpt transgene in G12 Chinese hamster
      cells. However, the nature of this silencing is still not clear. Here, we report
      that nickel ion exposure increases global H3K9 mono- and dimethylation, both of
      which are critical marks for DNA methylation and long-term gene silencing. In
      contrast to the up-regulation of global H3K9 dimethylation, nickel ions decreased
      the expression and activity of histone H3K9 specific methyltransferase G9a.
      Further investigation demonstrated that nickel ions interfered with the removal
      of histone methylation in vivo and directly decreased the activity of a Fe(II)-2
      oxoglutarate-dependent histone H3K9 demethylase in nuclear extract in vitro.
      These results are the first to show a histone H3K9 demethylase activity dependent
      on both iron and 2-oxoglutarate. Exposure to nickel ions also increased H3K9
      dimethylation at the gpt locus in G12 cells and repressed the expression of the
      gpt transgene. An extended nickel ion exposure led to increased frequency of the
      gpt transgene silencing, which was readily reversed by treatment with DNA
      demethylating agent 5-aza-2'-deoxycytidine. Collectively, our data strongly
      indicate that nickel ions induce transgene silencing by increasing histone H3K9
      dimethylation, and this effect is mediated by the inhibition of H3K9
      demethylation.

PMID- 16648470
TI  - SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a
      physical connection between the nuclear lamina and the cytoskeleton.
AB  - Nuclear migration and positioning within cells are critical for many
      developmental processes and are governed by the cytoskeletal network. Although
      mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links
      a novel family of nuclear envelope (NE) proteins that share a conserved C
      terminal SUN (Sad1/UNC-84 homology) domain. Analysis of Caenorhabditis elegans
      mutants has implicated UNC-84 in actin-mediated nuclear positioning by regulating
      NE anchoring of a giant actin-binding protein, ANC-1. Here, we report the
      identification of SUN1 as a lamin A-binding protein in a yeast two-hybrid screen.
      We demonstrate that SUN1 is an integral membrane protein located at the inner
      nuclear membrane. While the N-terminal domain of SUN1 is responsible for
      detergent-resistant association with the nuclear lamina and lamin A binding,
      lamin A/C expression is not required for SUN1 NE localization. Furthermore, SUN1
      does not interact with type B lamins, suggesting that NE localization is ensured
      by binding to an additional nuclear component(s), most likely chromatin.
      Importantly, we find that the luminal C-terminal domain of SUN1 interacts with
      the mammalian ANC-1 homologs nesprins 1 and 2 via their conserved KASH domain.
      Our data provide evidence of a physical nuclear-cytoskeletal connection that is
      likely to be a key mechanism in nuclear-cytoplasmic communication and regulation
      of nuclear position.

PMID- 16648471
TI  - Cells expressing murine RAD52 splice variants favor sister chromatid repair.
AB  - The RAD52 gene is essential for homologous recombination in the yeast
      Saccharomyces cerevisiae. RAD52 is the archetype in an epistasis group of genes
      essential for DNA damage repair. By catalyzing the replacement of replication
      protein A with Rad51 on single-stranded DNA, Rad52 likely promotes strand
      invasion of a double-stranded DNA molecule by single-stranded DNA. Although the
      sequence and in vitro functions of mammalian RAD52 are conserved with those of
      yeast, one difference is the presence of introns and consequent splicing of the
      mammalian RAD52 pre-mRNA. We identified two novel splice variants from the RAD52
      gene that are expressed in adult mouse tissues. Expression of these splice
      variants in tissue culture cells elevates the frequency of recombination that
      uses a sister chromatid template. To characterize this dominant phenotype
      further, the RAD52 gene from the yeast Saccharomyces cerevisiae was truncated to
      model the mammalian splice variants. The same dominant sister chromatid
      recombination phenotype seen in mammalian cells was also observed in yeast.
      Furthermore, repair from a homologous chromatid is reduced in yeast, implying
      that the choice of alternative repair pathways may be controlled by these
      variants. In addition, a dominant DNA repair defect induced by one of the
      variants in yeast is suppressed by overexpression of RAD51, suggesting that the
      Rad51-Rad52 interaction is impaired.

PMID- 16648472
TI  - Cortical thinning and hydrocephalus in mice lacking the immunoglobulin
      superfamily member CDO.
AB  - CDO is a cell surface immunoglobulin superfamily member that positively regulates
      myogenic differentiation in vitro and in vivo and signals to posttranslationally
      activate myogenic basic helix-loop-helix (bHLH) transcription factors. The Cdo
      gene is also expressed in the dorsal aspect and midline structures of the
      developing central nervous system, and mice lacking CDO on the C57BL/6 background
      display holoprosencephaly with approximately 80% penetrance, resulting in
      perinatal lethality. We report here that a fraction of Cdo-/- mice from this
      background have additional defects in brain development, including hydrocephalus
      and cortical thinning. Primary neural progenitor cultures from E14.5 Cdo-/-
      mutants display reduced proliferation, which may underlie the thinning. The
      cortical preplate and cortices of mutant animals also show reduced staining for
      beta-tubulin III, indicating defective neuronal differentiation. CDO levels are
      strongly increased in cultured C17.2 neuronal precursor cells stimulated to
      differentiate; modulation of CDO levels in these cells by overexpression or
      interfering RNA approaches enhances or diminishes differentiation, respectively.
      Cotransfection of CDO enhances the activity of the neurogenic bHLH factor,
      neurogenin1, in reporter assays and enhances heterodimerization of neurogenin1
      and E47. These results indicate that CDO promotes neuronal differentiation and
      support the hypothesis that CDO coordinates differentiation of multiple cell
      lineages by regulating the activity of tissue-specific bHLH factors.

PMID- 16648473
TI  - Nrf transcription factors in keratinocytes are essential for skin tumor
      prevention but not for wound healing.
AB  - The Nrf2 transcription factor is a key player in the cellular stress response
      through its regulation of cytoprotective genes. In this study we determined the
      role of Nrf2-mediated gene expression in keratinocytes for skin development,
      wound repair, and skin carcinogenesis. To overcome compensation by the related
      Nrf1 and Nrf3 proteins, we expressed a dominant-negative Nrf2 mutant (dnNrf2) in
      the epidermis of transgenic mice. The functionality of the transgene product was
      verified in vivo using mice doubly transgenic for dnNrf2 and an Nrf2-responsive
      reporter gene. Surprisingly, no abnormalities of the epidermis were observed in
      dnNrf2-transgenic mice, and even full-thickness skin wounds healed normally.
      However, the onset, incidence, and multiplicity of chemically induced skin
      papillomas were strikingly enhanced, whereas the progression to squamous cell
      carcinomas was unaltered. We provide evidence that the enhanced tumorigenesis
      results from reduced basal expression of cytoprotective Nrf target genes, leading
      to accumulation of oxidative damage and reduced carcinogen detoxification. Our
      results reveal a crucial role of Nrf-mediated gene expression in keratinocytes in
      the prevention of skin tumors and suggest that activation of Nrf2 in
      keratinocytes is a promising strategy to prevent carcinogenesis of this highly
      exposed organ.

PMID- 16648474
TI  - Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT
      control cardiomyocyte death and growth.
AB  - The calcium-calmodulin-activated protein phosphatase calcineurin functions as a
      key mediator of diverse biologic processes, including differentiation, apoptosis,
      growth, and adaptive responses, in part through dephosphorylation and activation
      of nuclear factor of activated T-cell (NFAT) transcription factors. Apoptosis
      signal-regulating kinase 1 (ASK1) is an upstream component of the mitogen
      activated protein kinases that serves as a pivotal regulator of cytokine-,
      oxidative-, and stress-induced cell death. Here, we performed a yeast two-hybrid
      screen with calcineurin B as bait, which identified ASK1 as a direct physical
      interacting partner. The C-terminal 218 amino acids of ASK1 were sufficient to
      mediate interaction with calcineurin B in yeast, as well as in mammalian cell
      lysates. Importantly, endogenous calcium binding B subunit (CnB) protein
      interacted with endogenous ASK1 protein in cardiomyocytes at baseline, suggesting
      that the interaction observed in yeast was of potential biologic relevance.
      Indeed, calcineurin directly dephosphorylated ASK1 at serine 967 using purified
      proteins or mammalian cell lysates. Dephosphorylation of ASK1 serine 967 by
      calcineurin promoted its disassociation from 14-3-3 proteins, resulting in ASK1
      activation. Calcineurin and ASK1 cooperatively enhanced cardiomyocyte apoptosis,
      while expression of a dominant negative ASK1 blocked calcineurin-induced
      apoptosis. Mouse embryonic fibroblasts deficient in ask1 were also partially
      resistant to calcineurin- or ionomycin-induced apoptosis. Finally, ASK1
      negatively regulated calcineurin-NFAT signaling indirectly through c-Jun NH2
      terminal kinase (JNK)- and p38-mediated phosphorylation of NFAT, which blocked
      calcineurin- and agonist-dependent hypertrophic growth of cardiomyocytes. Thus,
      ASK1 and calcineurin-NFAT constitute a feedback regulatory circuit in which
      calcineurin positively regulates ASK1 through direct dephosphorylation, while
      ASK1 negatively regulates calcineurin-NFAT signaling through p38- and JNK
      mediated NFAT phosphorylation.

PMID- 16648475
TI  - Nucleophosmin is essential for ribosomal protein L5 nuclear export.
AB  - Nucleophosmin (NPM/B23) is a key regulator in the regulation of a number of
      processes including centrosome duplication, maintenance of genomic integrity, and
      ribosome biogenesis. While the mechanisms underlying NPM function are largely
      uncharacterized, NPM loss results in severe dysregulation of developmental and
      growth-related events. We show that NPM utilizes a conserved CRM1-dependent
      nuclear export sequence in its amino terminus to enable its shuttling between the
      nucleolus/nucleus and cytoplasm. In search of NPM trafficking targets, we
      biochemically purified NPM-bound protein complexes from HeLa cell lysates.
      Consistent with NPM's proposed role in ribosome biogenesis, we isolated ribosomal
      protein L5 (rpL5), a known chaperone for the 5S rRNA. Direct interaction of NPM
      with rpL5 mediated the colocalization of NPM with maturing nuclear 60S ribosomal
      subunits, as well as newly exported and assembled 80S ribosomes and polysomes.
      Inhibition of NPM shuttling or loss of NPM blocked the nuclear export of rpL5 and
      5S rRNA, resulting in cell cycle arrest and demonstrating that NPM and its
      nuclear export provide a unique and necessary chaperoning activity to rpL5/5S.

PMID- 16648476
TI  - Direct control of cell cycle gene expression by proto-oncogene product ACTR, and
      its autoregulation underlies its transforming activity.
AB  - ACTR (also called AIB1 and SRC-3) was identified as a coactivator for nuclear
      receptors and is linked to multiple types of human cancer due to its frequent
      overexpression. However, the molecular mechanism of ACTR oncogenicity and its
      function independent of nuclear receptors remain to be defined. We demonstrate
      here that ACTR is required for both normal and malignant human cells to
      effectively enter S phase. RNA interference-mediated depletion and chromatin
      immunoprecipitation assays show that endogenous ACTR directly controls the
      expression of genes important for initiation of DNA replication, which include
      cdc6, cdc25A, MCM7, cyclin E, and Cdk2. Moreover, consistent with its critical
      role in cell cycle control, ACTR expression appears to be cell cycle regulated,
      which involves E2F. Interestingly, ACTR is recruited to its own promoter at the
      G1/S transition and activates its own expression, suggesting a positive feedback
      mechanism for ACTR action in the control of cell cycle progression and for its
      aberrant expression in cancers. Importantly, overexpression of ACTR alone
      transforms human mammary epithelial cells, which requires its association with
      E2F. These findings reveal a novel role for ACTR in cell cycle control and
      support the notion that the ability of aberrant ACTR to deregulate the cell cycle
      through E2F underlies its oncogenicity in human cancers.

PMID- 16648477
TI  - Determinants that control the specific interactions between TAB1 and p38alpha.
AB  - Previous studies have revealed that transforming growth factor-beta-activated
      protein kinase 1 (TAB1) interacts with p38alpha and induces p38alpha
      autophosphorylation. Here, we examine the sequence requirements in TAB1 and
      p38alpha that drive their interaction. Deletion and point mutations in TAB1
      reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for
      its interaction with p38alpha. Furthermore, a cryptic D-domain-like docking site
      was identified adjacent to the N terminus of Pro412, putting Pro412 in the
      phi(B)+3 position of the docking site. Through mutational analysis, we found that
      the previously identified hydrophobic docking groove in p38alpha is involved in
      this interaction, whereas the CD domain and ED domain are not. Furthermore,
      chimeric analysis with p38beta (which does not bind to TAB1) revealed a
      previously unidentified locus of p38alpha comprising Thr218 and Ile275 that is
      essential for specific binding of p38alpha to TAB1. Converting either of these
      residues to the corresponding amino acid of p38beta abolishes p38alpha
      interaction with TAB1. These p38alpha mutants still can be fully activated by
      p38alpha upstream activating kinase mitogen-activated protein kinase kinase 6,
      but their basal activity and activation in response to some extracellular stimuli
      are reduced. Adjacent to Thr218 and Ile275 is a site where large conformational
      changes occur in the presence of docking-site peptides derived from p38alpha
      substrates and activators. This suggests that TAB1-induced autophosphorylation of
      p38alpha results from conformational changes that are similar but unique to those
      seen in p38alpha interactions with its substrates and activating kinases.

PMID- 16648478
TI  - Dph3, a small protein required for diphthamide biosynthesis, is essential in
      mouse development.
AB  - The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique
      posttranslationally modified histidine residue, termed diphthamide, which serves
      as the only target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A.
      Diphthamide biosynthesis is carried out by five highly conserved proteins, Dph1
      to Dph5, and an as-yet-unidentified amidating enzyme. The evolutionary
      conservation of the complex diphthamide biosynthesis pathway throughout
      eukaryotes implies a key role for diphthamide in normal cellular physiology. Of
      the proteins required for diphthamide synthesis, Dph3 is the smallest, containing
      only 82 residues. In addition to having a role in diphthamide biosynthesis, Dph3
      is also involved in modulating the functions of the Elongator complex in yeast.
      To explore the physiological roles of Dph3 and to begin to investigate the
      function of diphthamide, we generated dph3 knockout mice and showed that dph3+/-
      mice are phenotypically normal, whereas dph3-/- mice, which lack the diphthamide
      modification on eEF-2, are embryonic lethal. Loss of both dph3 alleles causes a
      general delay in embryonic development accompanied by lack of allantois fusion to
      the chorion and increased degeneration and necrosis in neural tubes and is not
      compatible with life beyond embryonic day 11.5. The dph3-/- placentas also
      developed abnormally, showing a thinner labyrinth lacking embryonic erythrocytes
      and blood vessels. These results attest to the physiological importance of Dph3
      in development. The biological roles of Dph3 are also discussed.

PMID- 16648479
TI  - Deciphering the roles of the histone H2B N-terminal domain in genome-wide
      transcription.
AB  - Histone N-terminal domains are frequent targets of posttranslational
      modifications. Multiple acetylated lysine residues have been identified in the N
      terminal domain of H2B (K6, K11, K16, K17, K21, and K22), but little is known
      about how these modifications regulate transcription. We systematically mutated
      the N-terminal domain of histone H2B, both at known sites of lysine acetylation
      and elsewhere, and characterized the resulting changes in genome-wide expression
      in each mutant strain. Our results indicate that known sites of lysine
      acetylation in this domain are required for gene-specific transcriptional
      activation. However, the entire H2B N-terminal domain is principally required for
      the transcriptional repression of a large subset of the yeast genome. We find
      that the histone H2B repression (HBR) domain, comprised of residues 30 to 37, is
      necessary and sufficient for this repression. Many of the genes repressed by the
      HBR domain are located adjacent to telomeres or function in vitamin and
      carbohydrate metabolism. Deletion of the HBR domain also confers an increased
      sensitivity to DNA damage by UV irradiation. We mapped the critical residues in
      the HBR domain required for its repression function. Finally, comparisons of
      these data with previous studies reveal that a surprising number of genes are
      coregulated by the N-terminal domains of histone H2B, H3, and H4.

PMID- 16648480
TI  - RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle
      progression and induces cytokinesis failure.
AB  - KIF14 is a microtubule motor protein whose elevated expression is associated with
      poor-prognosis breast cancer. Here we demonstrate KIF14 accumulation in mitotic
      cells, where it associated with developing spindle poles and spindle
      microtubules. Cells at later stages of mitosis were characterized by the
      concentration of KIF14 at the midbody. Time-lapse microscopy revealed that strong
      RNA interference (RNAi)-mediated silencing of KIF14 induced cytokinesis failure,
      causing several rounds of endoreduplication and resulting in multinucleated
      cells. Additionally, less efficacious KIF14-specific short interfering RNAs
      (siRNAs) induced multiple phenotypes, all of which resulted in acute apoptosis.
      Our data demonstrate the ability of siRNA-mediated silencing to generate
      epiallelic hypomorphs associated with KIF14 depletion. Furthermore, the link we
      observed between siRNA efficacy and phenotypic outcome indicates that distinct
      stages during cell cycle progression are disrupted by the differential modulation
      of KIF14 expression.

PMID- 16648481
TI  - Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis.
AB  - The protein arginine methyltransferases (PRMTs) include a family of proteins with
      related putative methyltransferase domains that modify chromatin and regulate
      cellular transcription. Although some family members, PRMT1 and PRMT4, have been
      implicated in transcriptional modulation or intracellular signaling, the roles of
      other PRMTs in diverse cellular processes have not been fully established. Here,
      we report that PRMT2 inhibits NF-kappaB-dependent transcription and promotes
      apoptosis. PRMT2 exerted this effect by blocking nuclear export of IkappaB-alpha
      through a leptomycin-sensitive pathway, increasing nuclear IkappaB-alpha and
      decreasing NF-kappaB DNA binding. The highly conserved S-adenosylmethionine
      binding domain of PRMT2 mediated this effect. PRMT2 also rendered cells
      susceptible to apoptosis by cytokines or cytotoxic drugs, likely due to its
      effects on NF-kappaB. Mouse embryo fibroblasts from PRMT2 genetic knockouts
      showed elevated NF-kappaB activity and decreased susceptibility to apoptosis
      compared to wild-type or complemented cells. Taken together, these data suggest
      that PRMT2 inhibits cell activation and promotes programmed cell death through
      this NF-kappaB-dependent mechanism.

PMID- 16648482
TI  - Regulation of cardiac stress signaling by protein kinase d1.
AB  - In response to pathological stresses such as hypertension or myocardial
      infarction, the heart undergoes a remodeling process that is associated with
      myocyte hypertrophy, myocyte death, and fibrosis. Histone deacetylase 5 (HDAC5)
      is a transcriptional repressor of cardiac remodeling that is subject to
      phosphorylation-dependent neutralization in response to stress signaling. Recent
      studies have suggested a role for protein kinase C (PKC) and its downstream
      effector, protein kinase D1 (PKD1), in the control of HDAC5 phosphorylation.
      While PKCs are well-documented regulators of cardiac signaling, the function of
      PKD1 in heart muscle remains unclear. Here, we demonstrate that PKD1 catalytic
      activity is stimulated in cardiac myocytes by diverse hypertrophic agonists that
      signal through G protein-coupled receptors (GPCRs) and Rho GTPases. PKD1
      activation in cardiomyocytes occurs through PKC-dependent and -independent
      mechanisms. In vivo, cardiac PKD1 is activated in multiple rodent models of
      pathological cardiac remodeling. PKD1 activation correlates with phosphorylation
      dependent nuclear export of HDAC5, and reduction of endogenous PKD1 expression
      with small interfering RNA suppresses HDAC5 shuttling and associated
      cardiomyocyte growth. Conversely, ectopic overexpression of constitutively active
      PKD1 in mouse heart leads to dilated cardiomyopathy. These findings support a
      role for PKD1 in the control of pathological remodeling of the heart via its
      ability to phosphorylate and neutralize HDAC5.

PMID- 16648483
TI  - Role of histone deacetylase Rpd3 in regulating rRNA gene transcription and
      nucleolar structure in yeast.
AB  - The 35S rRNA genes at the RDN1 locus in Saccharomyces cerevisiae can be
      transcribed by RNA polymerase (Pol) II in addition to Pol I, but Pol II
      transcription is usually silenced. The deletion of RRN9 encoding an essential
      subunit of the Pol I transcription factor, upstream activation factor, is known
      to abolish Pol I transcription and derepress Pol II transcription of rRNA genes,
      giving rise to polymerase switched (PSW) variants. We found that deletion of
      histone deacetylase gene RPD3 inhibits the appearance of PSW variants in rrn9
      deletion mutants. This inhibition can be explained by the observed specific
      inhibition of Pol II transcription of rRNA genes by the rpd3Delta mutation. We
      propose that Rpd3 plays a role in the maintenance of an rRNA gene chromatin
      structure(s) that allows Pol II transcription of rRNA genes, which may explain
      the apparently paradoxical previous observation that rpd3 mutations increase,
      rather than decrease, silencing of reporter Pol II genes inserted in rRNA genes.
      We have additionally demonstrated that Rpd3 is not required for inhibition of Pol
      I transcription by rapamycin, supporting the model that Tor-dependent repression
      of the active form of rRNA genes during entry into stationary phase is Rpd3
      independent.

PMID- 16648484
TI  - Persistent transactivation by meis1 replaces hox function in myeloid
      leukemogenesis models: evidence for co-occupancy of meis1-pbx and hox-pbx
      complexes on promoters of leukemia-associated genes.
AB  - Homeobox transcription factors Meis1 and Hoxa9 promote hematopoietic progenitor
      self-renewal and cooperate to cause acute myeloid leukemia (AML). While Hoxa9
      alone blocks the differentiation of nonleukemogenic myeloid cell-committed
      progenitors, coexpression with Meis1 is required for the production of AML
      initiating progenitors, which also transcribe a group of hematopoietic stem cell
      genes, including Cd34 and Flt3 (defined as Meis1-related leukemic signature
      genes). Here, we use dominant trans-activating (Vp16 fusion) or trans-repressing
      (engrailed fusion) forms of Meis1 to define its biochemical functions that
      contribute to leukemogenesis. Surprisingly, Vp16-Meis1 (but not engrailed-Meis1)
      functioned as an autonomous oncoprotein that mimicked combined activities of
      Meis1 plus Hoxa9, immortalizing early progenitors, inducing low-level expression
      of Meis1-related signature genes, and causing leukemia without coexpression of
      exogenous or endogenous Hox genes. Vp16-Meis1-mediated transformation required
      the Meis1 function of binding to Pbx and DNA but not its C-terminal domain (CTD).
      The absence of endogenous Hox gene expression in Vp16-Meis1-immortalized
      progenitors allowed us to investigate how Hox alters gene expression and cell
      biology in early hematopoietic progenitors. Strikingly, expression of Hoxa9 or
      Hoxa7 stimulated both leukemic aggressiveness and transcription of Meis1-related
      signature genes in Vp16-Meis1 progenitors. Interestingly, while the Hoxa9 N
      terminal domain (NTD) is essential for cooperative transformation with wild-type
      Meis1, it was dispensable in Vp16-Meis1 progenitors. The fact that a dominant
      transactivation domain fused to Meis1 replaces the essential functions of both
      the Meis1 CTD and Hoxa9 NTD suggests that Meis-Pbx and Hox-Pbx (or Hox-Pbx-Meis)
      complexes co-occupy cellular promoters that drive leukemogenesis and that Meis1
      CTD and Hox NTD cooperate in gene activation. Chromatin immunoprecipitation
      confirmed co-occupancy of Hoxa9 and Meis1 on the Flt3 promoter.

PMID- 16648485
TI  - Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine
      phosphatase and regulation of beta-catenin's transcriptional activity.
AB  - Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion
      molecules involved in homophilic interactions, suggesting that RPTP outside-in
      signaling is coupled to cell contact formation. However, little is known about
      the mechanisms by which cell density regulates RPTP function. We show that the
      MAM family prototype RPTPkappa is cleaved by three proteases: furin, ADAM 10, and
      gamma-secretase. Cell density promotes ADAM 10-mediated cleavage and shedding of
      RPTPkappa. This is followed by gamma-secretase-dependent intramembrane
      proteolysis of the remaining transmembrane part to release the phosphatase
      intracellular portion (PIC) from the membrane, thereby allowing its translocation
      to the nucleus. When cells were treated with leptomycin B, a nuclear export
      inhibitor, PIC accumulated in nuclear bodies. PIC is an active protein tyrosine
      phosphatase that binds to and dephosphorylates beta-catenin, an RPTPkappa
      substrate. The expression of RPTPkappa suppresses beta-catenin's transcriptional
      activity, whereas the expression of PIC increases it. Notably, this increase
      required the phosphatase activity of PIC. Thus, both isoforms have acquired
      opposing roles in the regulation of beta-catenin signaling. We also found that
      RPTPmu, another MAM family member, undergoes gamma-secretase-dependent
      processing. Our results identify intramembrane proteolysis as a regulatory switch
      in RPTPkappa signaling and implicate PIC in the activation of beta-catenin
      mediated transcription.

PMID- 16648486
TI  - Early embryonic lethality due to targeted inactivation of DNA ligase III.
AB  - DNA ligases catalyze the joining of strand breaks in the phosphodiester backbone
      of duplex DNA and play essential roles in DNA replication, recombination, repair,
      and maintenance of genomic integrity. Three mammalian DNA ligase genes have been
      identified, and their corresponding ligases play distinct roles in DNA
      metabolism. DNA ligase III is proposed to be involved in the repairing of DNA
      single-strand breaks, but its precise role has not yet been demonstrated
      directly. To determine its role in DNA repair, cellular growth, and embryonic
      development, we introduced targeted interruption of the DNA ligase III (LIG3)
      gene into the mouse. Mice homozygous for LIG3 disruption showed early embryonic
      lethality. We found that the mutant embryonic developmental process stops at 8.5
      days postcoitum (dpc), and excessive cell death occurs at 9.5 dpc. LIG3 mutant
      cells have relatively normal XRCC1 levels but elevated sister chromatid exchange.
      These findings indicate that DNA ligase III is involved in essential DNA repair
      activities required for early embryonic development and therefore cannot be
      replaced by other DNA ligases.

PMID- 16648487
TI  - Functional interaction of CP2 with GATA-1 in the regulation of erythroid
      promoters.
AB  - We observed that binding sites for the ubiquitously expressed transcription
      factor CP2 were present in regulatory regions of multiple erythroid genes. In
      these regions, the CP2 binding site was adjacent to a site for the erythroid
      factor GATA-1. Using three such regulatory regions (from genes encoding the
      transcription factors GATA-1, EKLF, and p45 NF-E2), we demonstrated the
      functional importance of the adjacent CP2/GATA-1 sites. In particular, CP2 binds
      to the GATA-1 HS2 enhancer, generating a ternary complex with GATA-1 and DNA.
      Mutations in the CP2 consensus greatly impaired HS2 activity in transient
      transfection assays with K562 cells. Similar results were obtained by
      transfection of EKLF and p45 NF-E2 mutant constructs. Chromatin
      immunoprecipitation with K562 cells showed that CP2 binds in vivo to all three
      regulatory elements and that both GATA-1 and CP2 were present on the same GATA-1
      and EKLF regulatory elements. Adjacent CP2/GATA-1 sites may represent a novel
      module for erythroid expression of a number of genes. Additionally,
      coimmunoprecipitation and glutathione S-transferase pull-down experiments
      demonstrated a physical interaction between GATA-1 and CP2. This may contribute
      to the functional cooperation between these factors and provide an explanation
      for the important role of ubiquitous CP2 in the regulation of erythroid genes.

PMID- 16648488
TI  - Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2
      kinase pathway controlled by mTOR and uncoupled in breast cancer cells.
AB  - Hypoxia is a state of low oxygen availability that limits tumor growth. The
      mechanism of protein synthesis inhibition by hypoxia and its circumvention by
      transformation are not well understood. Hypoxic breast epithelial cells are shown
      to downregulate protein synthesis by inhibition of the kinase mTOR, which
      suppresses mRNA translation through a novel mechanism mitigated in transformed
      cells: disruption of proteasome-targeted degradation of eukaryotic elongation
      factor 2 (eEF2) kinase and activation of the regulatory protein 4E-BP1. In
      transformed breast epithelial cells under hypoxia, the mTOR and S6 kinases are
      constitutively activated and the mTOR negative regulator tuberous sclerosis
      complex 2 (TSC2) protein fails to function. Gene silencing of 4E-BP1 and eEF2
      kinase or TSC2 confers resistance to hypoxia inhibition of protein synthesis in
      immortalized breast epithelial cells. Breast cancer cells therefore acquire
      resistance to hypoxia by uncoupling oxygen-responsive signaling pathways from
      mTOR function, eliminating inhibition of protein synthesis mediated by 4E-BP1 and
      eEF2.

PMID- 16648489
TI  - Ral is both necessary and sufficient for the inhibition of myeloid
      differentiation mediated by Ras.
AB  - Hyperactivation of Ras is one of the most common abnormalities in acute myeloid
      leukemia. In experimental models, Ras inhibits myeloid differentiation, which is
      characteristic of leukemia; however, the mechanism through which it disrupts
      hematopoiesis is poorly understood. In multipotent FDCP-mix cells, Ras inhibits
      terminal neutrophil differentiation, thereby indefinitely extending their
      proliferative potential. Ras also strongly promotes the sensitivity of these
      cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). Using this
      model, we have dissected the signaling elements downstream of Ras to determine
      their relative contribution to the dysregulation of hematopoiesis. Cells
      expressing Ras mutants selectively activating Raf (Ras*T35S) or
      phosphatidylinositol 3-kinase (Ras*Y40C) did not significantly affect
      differentiation or proliferative capacity, whereas Ras*E37G (which selectively
      activates RalGEFs) perpetuated proliferation and blocked neutrophil development
      in a manner similar to that of Ras. Correspondingly, expression of constitutively
      active versions of these effectors confirmed the overriding importance of Ral
      guanine nucleotide exchange factors. Cells expressing Ras demonstrated
      hyperactivation of Ral, which itself was able to exactly mimic the phenotype of
      Ras, including hypersensitivity to GM-CSF. Conversely, dominant negative Ral
      promoted spontaneous neutrophil development. Ral, in turn, appears to influence
      differentiation through multiple effectors. These data show, for the first time,
      the importance of Ral in regulating differentiation and self-renewal in
      hematopoietic cells.

PMID- 16648490
TI  - Uncoupling the pleiotropic phenotypes of clk-1 with tRNA missense suppressors in
      Caenorhabditis elegans.
AB  - clk-1 encodes a demethoxyubiquinone (DMQ) hydroxylase that is necessary for
      ubiquinone biosynthesis. When Caenorhabditis elegans clk-1 mutants are grown on
      bacteria that synthesize ubiquinone (UQ), they are viable but have a pleiotropic
      phenotype that includes slowed development, behaviors, and aging. However, when
      grown on UQ-deficient bacteria, the mutants arrest development transiently before
      growing up to become sterile adults. We identified nine suppressors of the
      missense mutation clk-1(e2519), which harbors a Glu-to-Lys substitution. All
      suppress the mutant phenotypes on both UQ-replete and UQ-deficient bacteria.
      However, each mutant suppresses a different subset of phenotypes, indicating that
      most phenotypes can be uncoupled from each other. In addition, all suppressors
      restore the ability to synthesize exceedingly small amounts of UQ, although they
      still accumulate the precursor DMQ, suggesting that the presence of DMQ is not
      responsible for the Clk-1 phenotypes. We cloned six of the suppressors, and all
      encode tRNA(Glu) genes whose anticodons are altered to read the substituted Lys
      codon of clk-1(e2519). To our knowledge, these suppressors represent the first
      missense suppressors identified in any metazoan. The pattern of suppression we
      observe suggests that the individual members of the tRNA(Glu) family are
      expressed in different tissues and at different levels.

PMID- 16648491
TI  - Pause sites promote transcriptional termination of mammalian RNA polymerase II.
AB  - Polymerase II (Pol II) transcriptional termination depends on two independent
      genetic elements: poly(A) signals and downstream terminator sequences. The latter
      may either promote cotranscriptional RNA cleavage or pause elongating Pol II. We
      demonstrate that the previously characterized MAZ4 pause element promotes Pol II
      termination downstream of a poly(A) signal, dependent on both the proximity of
      the pause site and poly(A) signal and the strength of the poly(A) signal. The 5'-
      >3' exonuclease Xrn2 facilitates this pause-dependent termination by degrading
      the 3' product of poly(A) site cleavage. The human beta-actin gene also possesses
      poly(A) site proximal pause sequences, which like MAZ4 are G rich and promote
      transcriptional termination. Xrn2 depletion causes an increase in both steady
      state RNA and Pol II levels downstream of the beta-actin poly(A) site. Taken
      together, we provide new insights into the mechanism of pause site-mediated
      termination and establish a general role for the 5'-->3' exonuclease Xrn2 in Pol
      II termination.

PMID- 16648492
TI  - Hand-foot syndrome after dose-dense adjuvant chemotherapy for breast cancer: a
      case series.

PMID- 16648493
TI  - Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes
      genetically retargeted against carbonic anhydrase IX: first clinical experience.

PMID- 16648494
TI  - ASCO in the 21st century: challenges and opportunities--ASCO presidential address
      2005.

PMID- 16648495
TI  - Inherited genetic markers and cancer outcomes: personalized medicine in the
      postgenome era.

PMID- 16648496
TI  - Exploring dose-intensity: carefully comparing high-dose with low-dose external
      beam radiotherapy for prostate cancer.

PMID- 16648497
TI  - Reponses to topoisomerase-I inhibitors in extensive small-cell lung cancer:
      chance or chromosomes?

PMID- 16648498
TI  - Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with
      metastatic prostate cancer.
AB  - PURPOSE: The prognosis of metastatic prostate cancer significantly differs among
      individuals. While various clinical and biochemical prognostic factors for
      survival have been suggested, the progression and response to treatment of those
      patients may also be defined by host genetic factors. In this study, we evaluated
      genetic polymorphisms as prognostic predictors of metastatic prostate cancer.
      PATIENTS AND METHODS: One hundred eleven prostate cancer patients with bone
      metastasis at the diagnosis were enrolled in this study. Thirteen genetic
      polymorphisms were genotyped using polymerase chain reaction-restriction fragment
      length polymorphism or an automated sequencer with a genotyping software.
      RESULTS: Among the polymorphisms, the long allele (over 18 [CA] repeats) of
      insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA]
      repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse
      cancer-specific survival (P = .016 and .025 by logrank test, respectively). The
      presence of the long allele of either the IGF-I or CYP19 polymorphisms was an
      independent risk factor for death (P = .019 or .026, respectively). Furthermore,
      the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a
      stronger predictor for survival (P = .001). CONCLUSION: The prognosis of
      metastatic prostate cancer patients is suggested to be influenced by intrinsic
      genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may
      be novel predictors in prostate cancer patients with bone metastasis at the
      diagnosis.

PMID- 16648499
TI  - Dose-response in radiotherapy for localized prostate cancer: results of the Dutch
      multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78
      Gy.
AB  - PURPOSE: To determine whether a dose of 78 Gy improves outcome compared with a
      conventional dose of 68 Gy for prostate cancer patients treated with three
      dimensional conformal radiotherapy. PATIENTS AND METHODS: Between June 1997 and
      February 2003, stage T1b-4 prostate cancer patients were enrolled onto a
      multicenter randomized trial comparing 68 Gy with 78 Gy. Patients were stratified
      by institution, age, (neo)adjuvant hormonal therapy (HT), and treatment group.
      Four treatment groups (with specific radiation volumes) were defined based on the
      probability of seminal vesicle involvement. The primary end point was freedom
      from failure (FFF). Failure was defined as clinical failure or biochemical
      failure, according to the American Society of Therapeutic Radiation Oncology
      definition. Other end points were freedom from clinical failure (FFCF), overall
      survival (OS), and toxicity. RESULTS: Median follow-up time was 51 months. Of the
      669 enrolled patients, 664 were included in the analysis. HT was prescribed for
      143 patients. FFF was significantly better in the 78-Gy arm compared with the 68
      Gy arm (5-year FFF rate, 64% v 54%, respectively), with an adjusted hazard ratio
      of 0.74 (P = .02). No significant differences in FFCF or OS were seen between the
      treatment arms. There was no difference in late genitourinary toxicity of
      Radiation Therapy Oncology Group and European Organisation for Research and
      Treatment of Cancer grade 2 or more and a slightly higher nonsignificant
      incidence of late gastrointestinal toxicity of grade 2 or more. CONCLUSION: This
      multicenter randomized trial shows a significantly improved FFF in prostate
      cancer patients treated with a higher dose of radiotherapy.

PMID- 16648500
TI  - Impact of immune parameters on long-term survival in metastatic renal cell
      carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of immunologic
      prognostic factors in combination with established clinical prognostic factors in
      patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A
      total of 120 consecutive patients with mRCC received interleukin-2 (IL-2) -based
      immunotherapy. Baseline tumor biopsies were available from 85 of these patients.
      Potential prognostic factors were analyzed by univariate and multivariate
      analyses. RESULTS: Multivariate analysis (N = 120) identified high lactate
      dehydrogenase, lymph node metastases, low hemoglobin, low Karnofsky performance
      status, and bone metastases as independent poor prognostic clinical factors. The
      impact of these clinical factors has been demonstrated by others. Multivariate
      analysis (n = 85) also identified a high blood neutrophil count (> 6.0 x 10(9)/L;
      hazard ratio, 2.0; P = .015), the presence of intratumoral neutrophils (> 0
      cells/mm2 tumor tissue; hazard ratio, 2.3; P = .001), and low intratumoral CD57+
      natural killer cell count (< 50 cells/mm2 tumor tissue; hazard ratio, 2.1; P =
      .01) as independent poor prognostic immunologic factors. These three independent
      immunologic parameters had significant discriminatory power as supplemental risk
      factors in prognostic models based on the clinical risk factors, identifying
      subgroups within the favorable clinical group with estimated 5-year survival
      rates of 60%, 25%, and 0%, respectively. These findings were apparent in both our
      own prognostic model and in an extended Memorial Sloan-Kettering Cancer Center
      (New York, NY) prognostic model. CONCLUSION: This study points on five clinical
      and three supplemental immunologic independent prognostic factors of survival in
      patients with mRCC receiving IL-2.

PMID- 16648501
TI  - Mortality after major surgery for urologic cancers in specialized urology
      hospitals: are they any better?
AB  - PURPOSE: Specialty-specific hospitals and hospitals with a high volume of complex
      procedures have been shown to have better outcomes. We sought to determine
      whether a high volume of unrelated complex procedures or procedures in the same
      specialty area (urology) could translate into better outcomes after major
      urologic cancer surgery. METHODS: We performed a cross-sectional analysis of
      administrative discharge abstract data from the Nationwide Inpatient Sample of
      the Health Care Utilization Project for years 1998 to 2002. Comparison of outcome
      after three major urologic cancer-related surgical procedures (radical cystectomy
      [RC], radical nephrectomy [RN], and radical prostatectomy [RP]) at hospitals by
      procedure-specific volume, specialized urology status, and Leapfrog criteria was
      obtained to determine in-hospital mortality after the procedure. All patients in
      the database with a diagnosis of bladder, kidney, or prostate cancer being
      admitted for RC, RN, or RP between 1998 and 2002 were included. RESULTS: Neither
      specialized urology status nor meeting Leapfrog volume criteria for unrelated
      procedures was associated with lower odds of in-hospital mortality after any of
      the procedures examined. High-volume hospitals (for RC and RP) and moderate
      volume hospitals (for RP) were associated with lower odds of mortality. None of
      the examined hospital volume-related factors was associated with lower odds of
      mortality after RN. CONCLUSION: In-hospital mortality after two of three major
      urologic cancer procedures is affected only by procedure-specific volumes.
      Generalized process measures existing in hospitals performing a high volume of
      general urologic procedures or unrelated complex procedures may be less important
      determinants of procedure-specific outcomes in patients.

PMID- 16648502
TI  - Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences
      in five National Surgical Adjuvant Breast and Bowel Project node-positive
      adjuvant breast cancer trials.
AB  - PURPOSE: Locoregional failure after breast-conserving surgery is associated with
      increased risk of distant disease and death. The magnitude of this risk in
      patients receiving chemotherapy has not been adequately characterized. PATIENTS
      AND METHODS: Our study population included 2,669 women randomly assigned onto
      five National Surgical Adjuvant Breast and Bowel Project node-positive protocols
      (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole
      breast irradiation, and adjuvant systemic therapy. Cumulative incidences of
      ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence
      (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease
      free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models
      were used to model survival using clinical and pathologic factors jointly with
      IBTR or oLRR as time-varying predictors. RESULTS: Four hundred twenty-four
      patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR,
      and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and
      oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within
      5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen
      receptor status were significantly associated with IBTR. Nodal status and
      estrogen and progesterone receptor status were significantly associated with
      oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%,
      respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%,
      respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58
      (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively. CONCLUSION:
      Node-positive breast cancer patients who developed IBTR or oLRR had significantly
      poorer prognoses than patients who did not experience these events.

PMID- 16648503
TI  - Randomized phase III trial comparing irinotecan/cisplatin with
      etoposide/cisplatin in patients with previously untreated extensive-stage disease
      small-cell lung cancer.
AB  - PURPOSE: Etoposide and cisplatin (EP) has been a standard treatment for extensive
      disease small-cell lung cancer (SCLC). An earlier phase III trial reported
      improved survival for patients receiving irinotecan plus cisplatin (IP) versus
      EP. Our trial was designed to determine if a modified weekly regimen of IP would
      provide superior survival with less toxicity than EP. PATIENTS AND METHODS: The
      primary objective was to compare overall survival in extensive-disease SCLC
      patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were
      randomly assigned in 2:1 ratio to cisplatin 30 mg/m2 intravenously (IV) +
      irinotecan 65 mg/m2 IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m2 IV on
      day 1, and etoposide 120 mg/m2 IV on days 1 to 3 every 21 days for at least four
      cycles, until progressive disease, or until intolerable toxicity resulted.
      RESULTS: Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v
      86.5%; P < .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v
      11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P < .01), vomiting (12.5% v
      3.8%; P = .04), and diarrhea (21.3% v 0%; P < .01). There was no significant
      difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6
      months), or overall survival (median survival time, 9.3 months v 10.2 months; P =
      .74). CONCLUSION: Treatment with this dose and schedule of IP did not result in
      improved survival when compared with EP. Fewer patients receiving IP had grade
      3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with
      patients receiving EP, but more had grade 3/4 diarrhea and vomiting.

PMID- 16648504
TI  - Open-label, multicenter, randomized, phase III study comparing oral
      topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy
      naive patients with extensive-disease small-cell lung cancer.
AB  - PURPOSE: This open-label, randomized, multicenter phase III study compared oral
      topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin
      (PE) in patients with untreated extensive-disease small-cell lung cancer (ED
      SCLC). PATIENTS AND METHODS: A total of 784 patients were randomly assigned to
      either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n =
      389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n =
      395) every 21 days. RESULTS: Overall survival (primary end point) was similar
      between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year
      survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03
      (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute
      difference for noninferiority of TC relative to PE. Response rates were similar
      between groups (TC, 63% v PE, 69%). Time to progression was slightly but
      statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1
      weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred
      more frequently with PE (84% v 59%), whereas grade 3/4 anemia and
      thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%,
      respectively). Lung Cancer Symptom Scale scores were statistically better with
      PE, but the differences were small and of debatable clinical significance.
      CONCLUSION: Oral topotecan with cisplatin provides similar efficacy and
      tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and
      may provide greater patient convenience compared with intravenous etoposide and
      cisplatin.

PMID- 16648505
TI  - Phase I, pharmacokinetic, and pharmacodynamic study of intravenously administered
      Ad5CMV-p53, an adenoviral vector containing the wild-type p53 gene, in patients
      with advanced cancer.
AB  - PURPOSE: The purpose of this study was to assess the feasibility of administering
      Ad5CMV-p53, an adenoviral vector containing the wild-type p53 gene to patients
      with advanced malignancies, characterize the pertinent pharmacokinetic
      parameters, identify evidence of viral uptake in both normal and tumor tissue,
      and seek evidence of antitumor activity. METHODS: Patients were treated with
      escalating doses of Ad5CMV-p53 intravenously over 30 minutes on days 1, 2, and 3,
      every 28 days. The clearance of circulating Ad5CMV-p53 (INGN 201) DNA was
      characterized in the plasma and paired tumor and skin biopsies were performed in
      patients treated at the two highest dose levels to assess vector uptake into
      tissues. RESULTS: Seventeen patients received 36 courses of Ad5CMV-p53 at doses
      ranging from 3 x 10(10) to 3 x 10(12) virus particles (vp). Fatigue, nausea,
      vomiting, and fever were common, but rarely severe. Abnormalities of coagulation
      parameters, including decreases in fibrinogen and increases in fibrin degradation
      products at 3 x 10(12)vp, precluded additional dose escalation. Ad5CMV-p53 DNA
      could be detected in the plasma by polymerase chain reaction assay in the
      majority of patients at 14 days and 28 days at doses of 3 x 10(10) and higher.
      Six patients treated at 1 x 10(12)vp and 3 x 10(12)vp dose levels had Ad5CMV-p53
      DNA detected within paired tumor tissue collected day 4. CONCLUSION: Ad5CMV-p53
      can be safely and repetitively administered up to 1 x 10(12)vp intravenously
      daily for 3 consecutive days. The absence of severe toxicities, the presence of
      circulating adenovirus 24 hours after administration, and detectable p53
      transgene within tumor tissue distant from the site of administration
      demonstrates that systemic therapy with this adenoviral vector containing p53 is
      feasible.

PMID- 16648506
TI  - Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil
      and leucovorin in stage II and III carcinoma of the colon: results from National
      Surgical Adjuvant Breast and Bowel Project Protocol C-06.
AB  - PURPOSE: The primary aim of this study was to compare the relative efficacy of
      oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly
      intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS)
      and overall survival (OS) after primary surgery for colon carcinoma. PATIENTS AND
      METHODS: Between February 1997 and March 1999, 1,608 patients with stage II and
      III carcinoma of the colon were randomly assigned to receive either oral UFT+LV
      or intravenous FU+LV. RESULTS: Of the total patients, 47% had stage II colon
      cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3
      months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV
      versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246).
      The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional
      hazards model analyses with regard to age (< 60 v > or = 60 years), stage, or
      number of involved nodes (none v one to three v > or = four nodes) revealed no
      interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV
      arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with
      37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not
      differ between the two regimens, although convenience of care analysis favored
      UFT+LV. CONCLUSION: UFT+LV achieved similar DFS and OS when compared with an
      intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and
      generally well tolerated.

PMID- 16648507
TI  - Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality
      after surgery for hepatic colorectal metastases.
AB  - PURPOSE: Chemotherapy before resection of hepatic colorectal metastases (CRM) may
      cause hepatic injury and affect postoperative outcome. PATIENTS AND METHODS: Four
      hundred six patients underwent hepatic resection of CRM between 1992 and 2005.
      Pathologic review of the nontumorous liver was performed using established
      criteria for steatosis, steatohepatitis, and sinusoidal injury. The effect of
      chemotherapy and liver injury on perioperative outcome was analyzed. RESULTS: One
      hundred fifty-eight patients (38.9%) received no preoperative chemotherapy,
      whereas 248 patients (61.1%) did. The median duration of chemotherapy was 16
      weeks (range, 2 to 70 weeks). Chemotherapy consisted of fluoropyrimidine-based
      regimens (fluorouracil [FU] alone, 15.5%; irinotecan plus FU, 23.1%; and
      oxaliplatin plus FU, 19.5%) and other therapy (3.0%). On pathologic analysis, 36
      patients (8.9%) had steatosis, 34 (8.4%) had steatohepatitis, and 22 (5.4%) had
      sinusoidal dilation. Oxaliplatin was associated with sinusoidal dilation compared
      with no chemotherapy (18.9% v 1.9%, respectively; P < .001; odds ratio [OR] =
      8.3; 95% CI, 2.9 to 23.6). In contrast, irinotecan was associated with
      steatohepatitis compared with no chemotherapy (20.2% v 4.4%, respectively; P <
      .001; OR = 5.4; 95% CI, 2.2 to 13.5). Patients with steatohepatitis had an
      increased 90-day mortality compared with patients who did not have
      steatohepatitis (14.7% v 1.6%, respectively; P = .001; OR = 10.5; 95% CI, 2.0 to
      36.4). CONCLUSION: Steatohepatitis is associated with an increased 90-day
      mortality after hepatic surgery. In patients with hepatic CRM, the chemotherapy
      regimen should be carefully considered because the risk of hepatotoxicity is
      significant.

PMID- 16648508
TI  - Patient-controlled methylphenidate for cancer fatigue: a double-blind,
      randomized, placebo-controlled trial.
AB  - PURPOSE: To evaluate the effectiveness of patient-controlled methylphenidate as
      compared with placebo in cancer patients with fatigue, as measured by the
      Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). PATIENTS AND
      METHODS: Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 =
      no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL
      were included. Patients were randomly assigned to receive 5 mg methylphenidate or
      placebo every 2 hours as needed (maximum of four capsules a day), for 7 days.
      Patients completed a daily diary including study drug record and fatigue
      intensity. A research nurse telephoned patients daily to assess toxicity and
      fatigue level. All patients were offered open-label methylphenidate for 4 weeks.
      FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at
      baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was
      considered the primary end point. RESULTS: Of 112 patients randomly assigned, 52
      patients in the methylphenidate and 53 in the placebo group were assessable for
      analysis. Fatigue intensity improved significantly on day 8 in both the
      methylphenidate and placebo groups. However, there was no significant difference
      in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In
      open-label phase, fatigue intensity maintained low as compared with baseline. No
      significant toxicities were observed. CONCLUSION: Both methylphenidate and
      placebo resulted in significant symptom improvement. Methylphenidate was not
      significantly superior to placebo after 1 week of treatment. Longer study
      duration is justified. The role of daily telephone calls from a research nurse
      should be explored as a palliative care intervention.

PMID- 16648509
TI  - Response of asymptomatic brain metastases from small-cell lung cancer to systemic
      first-line chemotherapy.
AB  - PURPOSE: The purpose of this study was to investigate the radiologic response of
      asymptomatic brain metastases (BM) from small-cell lung cancer (SCLC) to first
      line systemic chemotherapy. PATIENTS AND METHODS: From 1990 to 2003, 181
      consecutive patients with SCLC were enrolled onto this study. Patients were
      examined by a neurologist on a regular basis. Magnetic resonance imaging (MRI) of
      the brain was performed routinely before (at diagnosis of SCLC) and after first
      line systemic chemotherapy. Patients were treated with combination chemotherapy
      consisting of cyclophosphamide, doxorubicin, and etoposide. Clinically manifest
      BM were treated with whole-brain radiotherapy (WBRT). The response rate (RR) of
      BM was assessed by changes in the size or the number of enhanced lesions on MRI
      using standard criteria. RESULTS: Synchronous asymptomatic BM were found in 24
      SCLC patients (13%). In six (27%) of the 22 assessable patients, the asymptomatic
      BM responded to systemic chemotherapy. A systemic response was found in 16
      patients (73%). All patients became symptomatic during follow-up. The symptom
      free survival did not differ between cranial responders and cranial
      nonresponders. CONCLUSION: The RR of asymptomatic BM from SCLC to systemic
      chemotherapy is 27% and evidently lower than the systemic RR. Future studies
      should focus on the possible beneficial effect of WBRT for patients with
      asymptomatic synchronous BM.

PMID- 16648510
TI  - Changes in neurologic function tests may predict neurotoxicity caused by
      ixabepilone.
AB  - PURPOSE: To investigate baseline factors and neurologic function tests (NFTs)
      that may predict the development of grade 2 or higher peripheral neuropathy (PN)
      after treatment with ixabepilone, an epothilone microtubule-stabilizing agent
      with antitumor activity. PATIENTS AND METHODS: Advanced breast cancer patients
      were treated with ixabepilone (6 mg/m2) for 5 consecutive days every 3 weeks in a
      phase II clinical trial. Physical examinations, questionnaires, nerve conduction
      studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the
      Grooved Pegboard Test (GPT), were performed at baseline and during subsequent
      cycles. RESULTS: Forty-seven patients assessable for PN received a median of five
      cycles of therapy (range, one to 22 cycles). Nine of these patients developed
      grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days
      (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients,
      with a median of 15 days (range, 6 to 346 days) after onset, but PN did not
      resolve in three patients during follow-ups at 76, 361, and 746 days after onset.
      GPT and changes of JTH scores at onset of PN were significantly different between
      patients with and without PN at comparable follow-up times (P = .006 and P =
      .002, respectively). Changes in GPT and JTH scores over the first two cycles were
      often associated with the development of PN by exploratory actuarial analysis.
      CONCLUSION: Serious ixabepilone-induced neuropathy was relatively rare on the
      treatment schedule used. NFTs, such as JTH and GPT, may have utility for
      predicting PN, but further testing is needed.

PMID- 16648511
TI  - Phase III Trial of an emulsion containing trolamine for the prevention of
      radiation dermatitis in patients with advanced squamous cell carcinoma of the
      head and neck: results of Radiation Therapy Oncology Group Trial 99-13.
AB  - PURPOSE: This multicentered phase III trial was designed to compare an emulsion
      containing trolamine against the usual supportive care within each participating
      institution for patients with head and neck cancer undergoing radiation therapy.
      PATIENTS AND METHODS: Patients with biopsy-proven squamous cell carcinoma of the
      oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of
      the following treatments: prophylactic trolamine emulsion, interventional
      trolamine emulsion, or declared institutional preference. The primary outcome was
      the reduction in grade 2 or higher skin toxicity, as per National Cancer
      Institute Common Toxicity Criteria version 2.0. Secondary outcomes included
      patient-reported quality of life (QOL). RESULTS: From October 2000 to April 2002,
      547 patients from 51 institutions were entered onto the trial. The average age
      was 59 years. Patients were predominately male (79%) and most continued to use
      tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were
      79%, 77%, and 79% in the prophylactic, interventional, and institutional
      preference arms of the study, respectively. No significant differences in QOL
      were found. CONCLUSION: The results of this trial demonstrate no advantage for
      the use of trolamine in reducing the incidence of grade 2 or higher radiation
      dermatitis or improving patient-reported QOL. The use of 15 different local
      standards of care highlights the need to continue research that will result in
      evidence-based recommendations to reduce the burden of radiation dermatitis.

PMID- 16648512
TI  - Prognostic significance of [18F]-misonidazole positron emission tomography
      detected tumor hypoxia in patients with advanced head and neck cancer randomly
      assigned to chemoradiation with or without tirapazamine: a substudy of Trans
      Tasman Radiation Oncology Group Study 98.02.
AB  - PURPOSE: To determine the association between tumor hypoxia, treatment regimen,
      and locoregional failure (LRF) in patients with stage III or IV squamous cell
      carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35
      fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and
      7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional
      fluorouracil during weeks 6 and 7 (chemoboost). PATIENTS AND METHODS: Forty-five
      patients were enrolled onto a hypoxic imaging substudy of a larger randomized
      trial. Pretreatment and midtreatment [18F]-fluoromisonidazole positron emission
      tomography scans (FMISO-PET) were performed 2 hours after tracer administration,
      with qualitative scoring of uptake in both primary tumors and nodes. RESULTS:
      Thirty-two patients (71%) had detectable hypoxia in either or both primary and
      nodal disease. In patients who received chemoboost, one of 10 patients without
      hypoxia had LRF compared with eight of 13 patients with hypoxia; the risk of LRF
      was significantly higher in hypoxic patients (exact log-rank, P = .038; hazard
      ratio [HR] = 7.1). By contrast, in patients who received the TPZ/CIS regimen,
      only one of 19 patients with hypoxic tumors had LRF; risk of LRF was
      significantly higher in chemoboost patients (P = .001; HR = 15). Similarly,
      looking at the primary site alone, in patients with hypoxic primaries, zero of
      eight patients treated with TPZ/CIS experienced failure locally compared with six
      of nine patients treated with chemoboost (P = .011; HR = 0). CONCLUSION: Hypoxia
      on FMISO-PET imaging, in patients receiving a nontirapazamine-containing
      chemoradiotherapy regimen, is associated with a high risk of LRF. Our data
      provide the first clinical evidence to support the experimental observation that
      tirapazamine acts by specifically targeting hypoxic tumor cells.

PMID- 16648513
TI  - Prognosis and management of patients with node-negative invasive breast carcinoma
      that is 1 cm or smaller in size (stage 1; T1a,bN0M0): a review of the literature.
AB  - PURPOSE: Mammographic screening has led to an increase in the number of small,
      node-negative breast cancers being diagnosed. Node-negative breast cancers that
      are < or = 1 cm are stage T1a,bN0M0. Controversy surrounds the prognosis of these
      patients with locoregional therapy only and the need for adjuvant systemic
      therapy. METHODS: We performed a comprehensive review of the literature
      describing outcome and prognostic factors in stage T1a,bN0M0 breast cancer. We
      also reviewed current guidelines for systemic therapy in these patients. RESULTS:
      Early studies reported 10-year relapse-free survival (RFS) rates higher than 90%
      without adjuvant systemic therapy, but some more recent data suggest inferior
      outcomes. High tumor grade is the most consistent factor associated with poor
      prognosis. Other adverse prognostic factors are younger age, lymphovascular
      invasion (LVI), high Ki-67, and larger tumors within the T1a,b subgroup. Patients
      with high-grade tumors and/or LVI may have 10-year RFS rates of less than 75% in
      the absence of systemic therapy. The prognostic significance of hormone receptor
      status is unclear. Current guidelines for the systemic management of early-stage
      breast cancer differ when applied to stage T1a,bN0M0, reflecting the
      controversial nature of the issue. CONCLUSION: Adjuvant systemic therapy is
      advisable for most patients with stage T1a,bN0M0 breast cancer who have grade 3
      tumors and/or LVI. Other T1a,bN0M0 cases should be considered for systemic
      therapy based on clinicopathologic factors with known prognostic significance and
      assessment of the risk-benefit ratio. More reliable tools are needed to assess
      the prognosis of patients with stage T1a,bN0M0 breast cancer and their potential
      to benefit from specific therapeutic agents.

PMID- 16648514
TI  - The attorney as the newest member of the cancer treatment team.

PMID- 16648516
TI  - A call for clinical trials: lipophilic statins may prove effective in treatment
      and prevention of particular breast cancer subtypes.

PMID- 16648517
TI  - Lipophilic statins merit additional study for breast cancer chemoprevention.

PMID- 16648518
TI  - Statins and breast cancer prevention: time for randomized controlled trials.

PMID- 16648522
TI  - Decisional priority in pediatric oncology revisited: involving children in
      decision making.

PMID- 16648523
TI  - Delivering medical care for patients with serious mental illness or promoting a
      collaborative model of recovery?
AB  - There is a tension between models of 'recovery', which are increasingly important
      in mental health policy and practice, and systematic models of care delivery
      based on the notion of 'chronic illness'. A collaborative approach is central to
      the development of high-quality recovery-oriented mental healthcare.

PMID- 16648524
TI  - Stalking of mental health professionals: an underrecognised problem.
AB  - Doctors and mental healthcare professionals are at greater risk of being stalked
      than the general population, particularly by their patients. Despite causing
      significant psychological distress, stalking remains underrecognised and poorly
      managed. Healthcare organisations should ensure appropriate policies are in place
      to aid awareness and minimise risk, including the provision of formal educational
      programmes.

PMID- 16648525
TI  - Euthanasia: the role of the psychiatrist.
AB  - Belgium has become one of the few countries in the world where euthanasia is
      legally allowed within a specific juridical framework. Even more unique is the
      inclusion of grounds for requesting euthanasia on the basis of mental suffering.
      Further refinement of the legal, medical and psychiatric approach to the issue is
      required in order to clear up essential practical and ethical matters.
      Psychiatrists and their professional organisations need to play a greater role in
      this ongoing debate and contribute from a clinical, scientific and ethical point
      of view.

PMID- 16648526
TI  - Pharmacological treatment for unipolar psychotic depression: Systematic review
      and meta-analysis.
AB  - BACKGROUND: The optimal pharmacological treatment of unipolar psychotic
      depression is uncertain. AIMS: To compare the clinical effectiveness of
      pharmacological treatments for patients with unipolar psychotic depression.
      METHOD: Systematic review and meta-analysis of randomised controlled trials.
      RESULTS: Ten trials were included in the review. We found no evidence that the
      combination of an antidepressant with an antipsychotic is more effective than an
      antidepressant alone. This combination was statistically more effective than an
      antipsychotic alone. CONCLUSIONS: Antidepressant monotherapy and adding an
      antipsychotic if the patient does not respond, or starting with the combination
      of an antidepressant and an antipsychotic, both appear to be appropriate options
      for patients with unipolar psychotic depression. However, clinically the balance
      between risks and benefits may suggest the first option should be preferred for
      many patients. Starting with an antipsychotic alone appears to be inadequate.

PMID- 16648527
TI  - Effect of month of birth on the risk of suicide.
AB  - BACKGROUND: Month of birth as a suicide risk factor has not been adequately
      explored. The findings of published studies are contradictory and inconclusive.
      AIMS: To examine the association between suicide and month of birth using suicide
      data for a 22-year period in England and Wales. The sample size of 26 915
      suicides greatly exceeds all previous studies. METHOD: We analysed all suicides
      (ICD-9 codes E950-959) and deaths from undetermined injury (E980-989) reported
      between 1979 and 2001 in England and Wales for persons born between 1955 and
      1966, using Poisson and negative binomial generalised linear models with seasonal
      components. RESULTS: Birth rates of people who later kill themselves show
      disproportionate excess for April, May and June compared with the other months.
      Overall, we found an increase of 17% in the risk of suicide for people born in
      the peak month (spring-early summer) compared with those born in the trough month
      (autumn-early winter); this risk increase was larger for women (29.6%) than for
      men (13.7%). CONCLUSIONS: The'month of birth'factor in suicide can be interpreted
      in terms of the foetal origins hypothesis. Our findings might have implications
      for our understanding of the multifaceted aetiology of suicide and may eventually
      offer new strategies for research and prevention.

PMID- 16648528
TI  - Prevalence and correlates of personality disorder in Great Britain.
AB  - BACKGROUND: Epidemiological data on personality disorders, comorbidity and
      associated use of services are essential for health service policy. AIMS: To
      measure the prevalence and correlates of personality disorder in a representative
      community sample. METHOD: The Structured Clinical Interview for DSM-IVAxis II
      disorders was used to measure personality disorder in 626 persons aged 16-74
      years in households in England, Scotland and Wales, in a two-phase survey.
      RESULTS: The weighted prevalence of personality disorder was 4.4% (95% CI 2.9
      6.7). Rates were highest among men, separated and unemployed participants in
      urban locations. High use of healthcare services was confounded by comorbid
      mental disorder and substance misuse. Cluster B disorders were associated with
      early institutional care and criminality. CONCLUSIONS: Personality disorder is
      common in the community, especially in urban areas. Services are normally
      restricted to symptomatic, help-seeking individuals, but a vulnerable group with
      cluster B disorders can be identified early, are in care during childhood and
      enter the criminal justice system when young. This suggests the need for
      preventive interventions at the public mental health level.

PMID- 16648529
TI  - Agoraphobia in adults: incidence and longitudinal relationship with panic.
AB  - BACKGROUND: Theories regarding how spontaneous panic and agoraphobia relate are
      based mostly on cross-sectional and/or clinic data. AIMS: To determine how
      spontaneous panic and agoraphobia relate longitudinally, and to estimate the
      incidence rate of and other possible risk factors for first-onset agoraphobia,
      using a general population cohort. METHOD: A sample of 1920 adults in east
      Baltimore were assessed in 1981-1982 and the mid-1990s with the Diagnostic
      Interview Schedule (DIS). Psychiatrist diagnoses were made in a subset of the
      sample at follow-up (n = 816). RESULTS: Forty-one new cases of DIS/DSM-III-R
      agoraphobia were identified (about 2 per 1000 person-years at risk). As expected,
      baseline DIS/DSM-III panic disorder predicted first incidence of agoraphobia (OR
      = 12, 95% CI 3.2-45), as did younger age, female gender and other age, female
      gender and other phobias. Importantly, baseline agoraphobia without spontaneous
      panic attacks also predicted first incidence of panic disorder (OR=3.9, 95% CI1.8
      8.4). Longitudinal relationships between panic disorder and psychiatrist
      confirmed agoraphobia were strong (panic before agoraphobia OR=20, 95% CI 2.3
      180; agoraphobia before panic OR=16, 95% CI 3.2-78). CONCLUSIONS: The implied one
      way causal relationship between spontaneous panic attacks and agoraphobia in DSM
      IV appears incorrect.

PMID- 16648530
TI  - Cognitive-behavioural therapy for substance use disorders in people with
      psychotic disorders: Randomised controlled trial.
AB  - BACKGROUND: Few randomised controlled trials have been aimed specifically at
      substance use reduction among people with psychotic disorders. AIMS: To
      investigate whether a 10-session intervention consisting of motivational
      interviewing and cognitive-behavioural therapy (CBT) was more efficacious than
      routine treatment in reducing substance use and improving symptomatology and
      general functioning. METHOD: A community sample of people with a psychotic
      disorder and who reported hazardous alcohol, cannabis and/or amphetamine use
      during the preceding month was recruited. Participants were randomly allocated to
      motivational interviewing/CBT (n = 65) or treatment as usual (n = 65), and were
      assessed on multiple outcomes at baseline, 15 weeks, 6 months and 12 months.
      RESULTS: There was a short-term improvement in depression and a similar trend
      with regard to cannabis use among participants who received the motivational
      interviewing/CBT intervention, together with effects on general functioning at 12
      months. There was no differential benefit of the intervention on substance use at
      12 months, except for a potentially clinically important effect on amphetamine
      use. CONCLUSIONS: The motivational interviewing/CBT intervention was associated
      with modest improvements.

PMID- 16648531
TI  - Antidepressant therapy and C-reactive protein levels.
AB  - BACKGROUND: Major depression is associated with activation of the inflammatory
      response. AIMS: To examine C-reactive protein levels in depression and to
      determine the impact of selective serotonin reuptake inhibitor (SSRI) therapy.
      METHOD: A two-part study. In study 1, which used a between-subjects design, C
      reactive protein was measured in 32 patients (20 currently depressed, 12
      euthymic) with a history of DSM-IV major depression, all of whom were treated
      with an SSRI, and in a healthy comparison group (n = 20). Study 2 employed a
      within-subject design: C-reactive protein was measured in 20 patients with major
      depression both before and after SSRI treatment. RESULTS: In study 1, C-reactive
      protein levels did not differ between the group with depressive disorder (either
      currently depressed or euthymic) treated with SSRIs and the healthy group. In
      study 2 the protein levels dropped significantly following treatment with
      antidepressant medication. CONCLUSIONS: Following SSRI treatment for major
      depression there is a significant drop in C-reactive protein concentrations
      whether or not the depression resolves. These findings indicate that
      antidepressants induce an anti-inflammatory response independent of
      antidepressant action.

PMID- 16648532
TI  - Military deployment to the Gulf War as a risk factor for psychiatric illness
      among US troops.
AB  - BACKGROUND: Several studies document an excess of psychiatric symptoms among
      veterans of the the 1991 Gulf War. However, little is known about the prevalence
      of psychiatric disorders in those who were deployed to that conflict. AIMS: To
      compare the 12-month prevalence and associated risk factors for DSM Axis I
      psychiatric diagnoses between random samples of Gulf War-deployed veterans and
      veterans of the same era not deployed to the Persian Gulf (era veterans). METHOD:
      Interview data from 967 Gulf War veterans and 784 era veterans were examined to
      determine current health status, medical conditions, symptoms and Axis I
      psychiatric disorders. Logistic regression models evaluated risk factors for
      psychiatric disorder. RESULTS: Gulf War veterans had a significantly higher
      prevalence of psychiatric diagnoses, with twice the prevalence of anxiety
      disorders and depression. Lower rank, female gender and divorced or single
      marital status were significant independent predictors of psychiatric disorder.
      CONCLUSIONS: Deployment to the Gulf War is associated with a range of mental
      health outcomes more than 10 years after deployment.

PMID- 16648533
TI  - Quality of life of people with dementia in residential care homes.
AB  - BACKGROUND: Many people with dementia live in residential homes, but little is
      known about their quality of life. AIMS: To compare the views of residents with
      dementia with the views of staff as to their quality of life, and to look at
      factors associated with these ratings. METHOD: The Quality of Life in Alzheimer's
      Disease (QoL-AD) scale was used to rate residents' and staff's perceptions of the
      quality of life of 238 residents of 24 residential homes in the UK. RESULTS:
      There were 119 QoL-AD scales completed by both residents and staff. For the
      residents, high QoL-AD scores strongly correlated with lower scores for
      depression (rho = -0.53, P < 0.0001) and anxiety (rho = -0.50, P < 0.001). In
      contrast, better quality of life as rated by staff correlated most strongly with
      increased dependency (rho = -0.53, P < 0.001) and behaviour problems (rho = 
      0.40, P < 0.001). CONCLUSIONS: The QoL-AD could be used as an effective measure
      of the quality of life of people with dementia in residential homes. Whereas mood
      was the main predictor of residents'own assessment of their quality of life,
      staff ratings were strongly linked with dependency. Staff should be aware that
      mood rather than level of dependency has a greater impact on residents' quality
      of life.

PMID- 16648534
TI  - Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of
      Mental Health and Well-Being.
AB  - BACKGROUND: Large-scale community studies of the prevalence of mental disorders
      using standardised assessment tools are rare in sub-Saharan Africa. AIMS: To
      conduct such a study. METHOD: Multistage stratified clustered sampling of
      households in the Yoruba-speaking parts of Nigeria. Face-to-face interviews used
      the World Mental Health version of the Composite International Diagnostic
      Interview (WMH-CIDI). RESULTS: Of the 4984 people interviewed (response rate
      79.9%), 12.1% had a lifetime rate of at least one DSM-IV disorder and 5.8% had 12
      month disorders. Anxiety disorders were the most common (5.7% lifetime, 4.1% 12
      month rates) but virtually no generalised anxiety or post-traumatic stress
      disorder were identified. Of the 23% who had seriously disabling disorders, only
      about 8% had received treatment in the preceding 12 months. Treatment was mostly
      provided by general medical practitioners; only a few were treated by alternative
      practitioners such as traditional healers. CONCLUSIONS: The observed low rates
      seem to reflect demographic and ascertainment factors. There was a large burden
      of unmet need for care among people with serious disorders.

PMID- 16648535
TI  - Quantifying the contributions of three types of information to the prediction of
      criminal conviction using the receiver operating characteristic.
AB  - BACKGROUND: Quantifying the contributions that different types of information
      make to the accurate prediction of offending offers the prospects of improved
      practice and better use of resources. AIMS: To quantify the contributions made by
      three types of information--demographic data alone, demographic and criminal
      record and demographic, criminal record and legal class of disorder--to the
      prediction of criminal conviction in patients. METHOD: All 425 patients
      discharged from the three special (high secure) hospitals in England and Wales
      over 2 years were followed for 10.5 years. The contribution of each type of
      information was described in terms of the area under the receiver operating
      characteristic curve (AUC) and the number needed to detain (NND). RESULTS: The
      AUC values using the three types of information were 0.66, 0.72 and 0.73
      respectively. Prediction based on the full model using an optimal probability cut
      off implies an NND of 2. The AUCs for serious offences were 0.67, 0.69 and 0.75
      respectively. CONCLUSIONS: For long-term prediction of conviction on any charge,
      information on legal class adds little to the accuracy of predictions made using
      only a patient's age, gender and criminal record. In the prediction of serious
      offences alone the contribution of legal class is significant.

PMID- 16648536
TI  - Accuracy and utility of post-conviction polygraph testing of sex offenders.
AB  - BACKGROUND: Polygraphy is used increasingly in the treatment and supervision of
      sex offenders, but little research has addressed its accuracy in this setting, or
      linked accuracy with utility. AIMS: To investigate the utility and accuracy of
      polygraphy in post-conviction testing of community-based sex offenders. METHOD: A
      self-report measure examined the experiences of offenders with polygraphy.
      RESULTS: Based on self-report, the polygraph's accuracy was approximately 85%.
      False negatives and false positives were not associated with demographic
      characteristics, personality variables or IQ. The majority of offenders found the
      polygraph to be helpful in both treatment and supervision. Nine percent of
      offenders claimed to have made false disclosures; these individuals had higher
      scores on ratings of neuroticism and lower scores on ratings of
      conscientiousness. CONCLUSIONS: These results support the view that the polygraph
      is both accurate and useful in the treatment and supervision of sex offenders.

PMID- 16648537
TI  - Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance
      imaging study using optimised voxel-based morphometry.
AB  - The genesis of Tourette syndrome is still unknown, but a core role for the
      pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed.
      Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys
      with Tourette syndrome and 15 age-matched controls using optimised voxel-based
      morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were
      found bilaterally in the ventral putamen. Regional decreases in grey matter were
      observed in the left hippocampal gyrus. This unbiased analysis confirmed an
      association between striatal abnormalities and Tourette syndrome, and the
      hippocampal volume alterations indicate an involvement of temporolimbic pathways
      of the CSTC in the syndrome.

PMID- 16648538
TI  - Views of child psychiatrists on physical contact with patients.
AB  - The appropriateness and therapeutic value of physical contact with children is
      under increasing scrutiny. We conducted a postal questionnaire and telephone
      survey of consultant child and adolescent psychiatrists within Great Britain to
      investigate attitudes of specialists towards physical contact with their patients
      in different clinical contexts. Here we report that psychiatrists tend to
      restrict physical contact to the minimum essential for patient comfort or safety.
      Decision-making about contact is primarily influenced by professional experience
      and training. This conservative approach to physical contact with patients has
      implications for clinical practice and requires to be better informed by
      evidence.

PMID- 16648539
TI  - Cognitive-behavioural therapy for bipolar disorder.

PMID- 16648540
TI  - Trial of risperidone in India--concerns.

PMID- 16648541
TI  - Trial of risperidone in India--concerns.

PMID- 16648542
TI  - Trial of risperidone in India--concerns.

PMID- 16648544
TI  - Antiparkinsonian prescription and extrapyramidal symptoms.

PMID- 16648545
TI  - Treatment of borderline personality disorder.

PMID- 16648546
TI  - Neurobehavioural characteristics and relapse in addiction.

PMID- 16648547
TI  - Identification of a novel bile acid in swans, tree ducks, and geese:
      3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.
AB  - By HPLC, a taurine-conjugated bile acid with a retention time different from that
      of taurocholate was found to be present in the bile of the black-necked swan,
      Cygnus melanocoryphus. The bile acid was isolated and its structure, established
      by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl
      amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The
      compound was shown to have chromatographic and spectroscopic properties that were
      identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha
      trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from
      ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha
      trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in
      the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the
      subfamily Anserinae (swans and geese) but not in other subfamilies in the
      Anatidae family. It was also not present in species from the other two families
      of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic
      acid is a new primary bile acid that is present in the biliary bile acids of
      swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic
      acid.

PMID- 16648548
TI  - Molecular biomarkers: their increasing role in the diagnosis, characterization,
      and therapy guidance in pancreatic cancer.
AB  - The rapidly expanding knowledge of the pathogenesis of pancreatic cancer at the
      molecular level is providing new targets for disease characterization, early
      diagnosis, and drug discovery and development. Gene mutation analysis has
      provided insight on the pathogenesis and progression from preinvasive lesions to
      invasive cancer. Gene and protein expression profiling has advanced our
      understanding of pancreatic ductal adenocarcinoma identifying genes that are
      highly expressed in pancreatic cancers, providing more insight into the
      clinicopathologic features of pancreatic cancer, and revealing novel features
      related to the process of tissue invasion by these tumors. The increasing
      knowledge of the pathway activation profile in pancreatic cancer is yielding new
      targets but also new markers to select patients and guide and predict therapy
      efficacy. The discovery of genetic factors of which the presence predisposes
      pancreatic cancer to successful targeting, such as the association of
      BRCA2/Fanconi anemia genes defects and sensitivity to mitomycin C, will
      eventually lead to a more individualized treatment approach. In summary, several
      decades of intensive research have originated multiple factors or biomarkers that
      are likely to be helpful in the diagnosis, characterization, and therapy
      selection of pancreatic cancer patients. A deep understanding of the relative
      relevance of each biomarker will be key to efficiently diagnose this disease and
      direct our patients towards the drugs more likely to be of benefit based on their
      particular profile. The development of new preclinical models is of paramount
      importance to achieve these goals.

PMID- 16648549
TI  - Promise of vitamin D analogues in the treatment of hyperproliferative conditions.
AB  - 1Alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3; calcitriol] is best known as a
      hormone involved in calcium homeostasis but is also a potent antiproliferative
      agent in many cell types, particularly epithelial cells. 1Alpha,25(OH)2D3
      mediates its actions through a classic steroid hormone-like transcriptional
      mechanism by influencing the expression of hundreds of genes. Effects of
      1alpha,25(OH)2D3 have been observed on expression of cell cycle regulators,
      growth factors and their receptors, apoptotic machinery, metastatic potential,
      and angiogenesis; all of which have some effect on hyperproliferative conditions.
      This minireview focuses on the anticancer potential of 1alpha,25(OH)2D3 and its
      analogues by summarizing the promising data from animal and human trials of
      1alpha,25(OH)2D3 and some of the more interesting synthetic vitamin D analogues
      in the treatment of a variety of different animal cancer models and in human
      patients with advanced cancer. Optimal administration of vitamin D analogues is
      only just being achieved with high-dose intermittent administration overcoming
      bioavailability and hypercalcemia problems and combination therapy with cytotoxic
      agents (taxols and cisplatins), antiresorptive agents (bisphosphonates), or
      cytochrome P450 inhibitors being attempted. Although the potential of vitamin D
      as an antiproliferative drug has been realized in the treatment of psoriasis and
      in parathyroid cell hyperplasia associated with secondary hyperparathyroidism,
      the search for an anticancer treatment incorporating a vitamin D analogue remains
      elusive.

PMID- 16648550
TI  - Molecular alterations after Polo-like kinase 1 mRNA suppression versus
      pharmacologic inhibition in cancer cells.
AB  - Multiple roles within mitosis have been assigned to Polo-like kinase 1 (Plk1),
      making it an attractive candidate for mitotic targeting of cancer cells. We have
      employed chimeric antisense oligonucleotides to investigate the molecular
      alterations after targeted interference with Plk1 in RKO human colon
      adenocarcinoma and PC3 prostate cancer cells. Suppression of Plk1 mRNA resulted
      in a dramatic increase of the mitotic index followed by the onset of apoptosis.
      Mitotically arrested cells displayed randomly separated condensed chromosomes and
      the occurrence of multiple spindle poles with well-formed asters. Induction of
      apoptosis was strictly dependent on cell cycle progression: Genetically
      engineered RKO cells with inducible expression of the cyclin-dependent kinase
      inhibitor p27(Kip1) were completely refractory to Plk1 depletion-induced
      apoptosis when they were arrested in the G1 phase of the cell cycle. Various
      mitotic markers, including MPM-2, cdc25c, cyclin B1, or phosphorylated histone
      H3, were investigated to explore the molecular consequences of Plk1 depletion.
      Whereas most marker proteins showed similar alterations compared with treatment
      with paclitaxel, cdc25c was fully phosphorylated solely in paclitaxel-treated
      cells but only partially phosphorylated in Plk1-depleted cells, although both
      treatments caused a profound mitotic arrest. This differential phosphorylation of
      cdc25c was used to test whether a pharmacologic inhibitor of Plk1 would exert the
      same cellular effects as interference with Plk1 on a mRNA level. It was found
      that the differential electrophoretic mobility of cdc25c can serve as a reliable
      molecular marker to track inhibition of Plk1 by small-molecule inhibitors within
      a cell.

PMID- 16648551
TI  - Intracellular uptake and intracavitary targeting of folate-conjugated liposomes
      in a mouse lymphoma model with up-regulated folate receptors.
AB  - The folate receptor is overexpressed in a broad spectrum of malignant tumors and
      represents an attractive target for selective delivery of anticancer agents to
      folate receptor-expressing tumors. This study examines folate-lipid conjugates as
      a means of enhancing the tumor selectivity of liposome-encapsulated drugs in a
      mouse lymphoma model. Folate-derivatized polyethylene glycol (PEG3350)-distearoyl
      phosphatidylethanolamine was post-loaded at various concentrations into the
      following preparations: radiolabeled PEGylated liposomes, PEGylated liposomes
      labeled in the aqueous compartment with dextran fluorescein, and PEGylated
      liposomal doxorubicin (PLD, Doxil). We incubated folate-targeted radiolabeled or
      fluorescent liposomes with mouse J6456 lymphoma cells up-regulated for their
      folate receptors (J6456-FR) to determine the optimal ligand concentration
      required in the lipid bilayer for liposomal cell association, and to examine
      whether folate-targeted liposomes are internalized by J6456-FR cells in
      suspension. Liposomal association with cells was quantified based on
      radioactivity and fluorescence-activated cell sorting analysis, and
      internalization was assessed by confocal fluorescence microscopy. We found an
      optimal ligand molar concentration of approximately 0.5% using our ligand. A
      substantial lipid dose-dependent increase in cell-associated fluorescence was
      found in folate-targeted liposomes compared with nontargeted liposomes. Confocal
      depth scanning showed that a substantial amount of the folate-targeted liposomes
      are internalized by J6456-FR cells. Binding and uptake of folate-targeted PLD by
      J6456-FR cells were also observed in vivo after i.p. injection of folate-targeted
      PLD in mice bearing ascitic J6456-FR tumors. The drug levels in ascitic tumor
      cells were increased by 17-fold, whereas those in plasma were decreased by 14
      fold when folate-targeted PLD were compared with nontargeted PLD in the i.p.
      model. Folate-targeted liposomes represent an attractive approach for the
      intracellular delivery of drugs to folate receptor-expressing lymphoma cells and
      seem to be a promising tool for in vivo intracavitary drug targeting.

PMID- 16648552
TI  - Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin
      tumors and malignant transformation of papillomas to carcinomas.
AB  - Solar UV radiation-induced immunosuppression is a risk factor for nonmelanoma
      skin cancer. Interleukin (IL)-12 has been shown to possess antitumor activity and
      inhibit the immunosuppressive effects of UV radiation in mice. In this study, we
      generated IL-12 knockout (KO) mice on a C3H/HeN background to characterize the
      role of IL-12 in photocarcinogenesis. After exposure of the mice to UVB (180
      mJ/cm2) radiation thrice a week for 35 weeks, the development of UV-induced
      tumors was more rapid and the tumor multiplicity and tumor size were
      significantly higher in IL-12 KO mice than their wild-type (WT) counterparts (P <
      0.05-0.001). Moreover, the malignant transformation of UVB-induced papillomas to
      carcinomas was higher in IL-12 KO mice in terms of carcinoma incidence (55%, P <
      0.001), carcinoma multiplicity (77%, P < 0.001), and carcinoma size (81%, P <
      0.001). As IL-12 has the ability to repair UV-induced DNA damage, we determined
      this effect in our in vivo IL-12 KO mouse model. We found that UVB-induced DNA
      damage in the form of cyclobutane pyrimidine dimers was removed or repaired more
      rapidly in WT mice than IL-12 KO mice. Similarly, the UVB-induced sunburn cell
      formation is primarily a consequence of DNA damage. It was observed that UVB
      induced sunburn cells were repaired rapidly in WT mice compared with IL-12 KO
      mice. The rapid removal or repair of UV-induced cyclobutane pyrimidine dimers or
      sunburn cells will result in reduced risk of photocarcinogenesis. Taken together,
      our data show that IL-12 deficiency is associated with the greater risk of
      photocarcinogenesis in mice, and this may be due to reduction in damaged DNA
      repair ability.

PMID- 16648553
TI  - Integrin-linked kinase functions as a downstream mediator of endothelin-1 to
      promote invasive behavior in ovarian carcinoma.
AB  - The endothelin-1 (ET-1) axis represents a novel target in several malignancies,
      including ovarian carcinoma. Upon being activated, the endothelin A receptor
      (ET(A)R) mediates multiple tumor-promoting activities, including mitogenesis,
      escape from apoptosis, angiogenesis, metastasis-related protease activation,
      epithelial-mesenchymal transition, and invasion. Integrin-linked kinase (ILK) is
      a multidomain focal adhesion protein that conveys intracellular signaling
      elicited by beta1-integrin and growth factor receptors. In this study, we
      investigate whether the signaling triggered by ET(A)R leading to an aggressive
      phenotype is mediated by an ILK-dependent mechanism. In HEY and OVCA 433 ovarian
      carcinoma cell lines, activation of ET(A)R by ET-1 enhances the expression of
      alpha2beta1 and alpha3beta1 integrins. ILK activity increases as ovarian cancer
      cells adhere to type I collagen through beta1 integrin signaling, and do so to a
      greater extent on ET-1 stimulation. ET-1 increases ILK mRNA and protein
      expression and activity in a time- and concentration-dependent manner. An ILK
      small-molecule inhibitor (KP-392) or transfection with a dominant-negative ILK
      mutant effectively blocks the phosphorylation of downstream signals, Akt and
      glycogen synthase kinase-3beta. The blockade of ET-1/ET(A)R-induced ILK activity
      results in an inhibition of matrix metalloproteinase activation as well as of
      cell motility and invasiveness in a phosphoinositide 3 kinase-dependent manner.
      In ovarian carcinoma xenografts, ABT-627, a specific ET(A)R antagonist,
      suppresses ILK expression, Akt and glycogen synthase kinase-3beta
      phosphorylation, and tumor growth. These data show that ILK functions as a
      downstream mediator of the ET-1/ET(A)R axis to potentiate aggressive cellular
      behavior. Thus, the ILK-related signaling cascade can be efficiently targeted by
      pharmacologic blockade of ET(A)R.

PMID- 16648554
TI  - Molecular targets for apigenin-induced cell cycle arrest and apoptosis in
      prostate cancer cell xenograft.
AB  - Apigenin (4',5,7-trihydroxyflavone) is a promising chemopreventive agent
      abundantly present in fruits and vegetables that has been shown to promote cell
      cycle arrest and apoptosis in various malignant cell lines. To determine whether
      pharmacologic intervention with apigenin has a direct growth inhibitory effect on
      human prostate tumors implanted in athymic nude mice, we examined cell cycle
      regulatory molecules as precise molecular targets of apigenin action. Apigenin
      feeding by gavage to these mice at doses of 20 and 50 microg/mouse/d in 0.2 mL of
      a vehicle containing 0.5% methyl cellulose and 0.025% Tween 20 resulted in
      significant decreases in tumor volume and mass of androgen-sensitive 22Rv1 and
      androgen-insensitive PC-3-implanted cells. Oral intake of apigenin resulted in
      dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,
      INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of
      cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6;
      (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the
      binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the
      binding of cyclin E toward cdk2 in both types of tumors. In addition, apigenin
      feeding resulted in stabilization of p53 by phosphorylation at serine 15 in 22Rv1
      tumors, which seems to exhibit p53-dependent growth inhibitory responses.
      Apigenin intake by these mice also resulted in induction of apoptosis, which
      positively correlated with serum and tumor apigenin levels. Taken together, this
      is the first systematic in vivo study showing the involvement of cell cycle
      regulatory proteins as potential molecular targets of apigenin.

PMID- 16648555
TI  - Integrating data on DNA copy number with gene expression levels and drug
      sensitivities in the NCI-60 cell line panel.
AB  - Chromosome rearrangement, a hallmark of cancer, has profound effects on
      carcinogenesis and tumor phenotype. We used a panel of 60 human cancer cell lines
      (the NCI-60) as a model system to identify relationships among DNA copy number,
      mRNA expression level, and drug sensitivity. For each of 64 cancer-relevant
      genes, we calculated all 4,096 possible Pearson's correlation coefficients
      relating DNA copy number (assessed by comparative genomic hybridization using
      bacterial artificial chromosome microarrays) and mRNA expression level
      (determined using both cDNA and Affymetrix oligonucleotide microarrays). The
      analysis identified an association of ERBB2 overexpression with 3p copy number, a
      finding supported by data from human tumors and a mouse model of ERBB2-induced
      carcinogenesis. When we examined the correlation between DNA copy number for all
      353 unique loci on the bacterial artificial chromosome microarray and drug
      sensitivity for 118 drugs with putatively known mechanisms of action, we found a
      striking negative correlation (-0.983; 95% bootstrap confidence interval, -0.999
      to -0.899) between activity of the enzyme drug L-asparaginase and DNA copy number
      of genes near asparagine synthetase in the ovarian cancer cells. Previous
      analysis of drug sensitivity and mRNA expression had suggested an inverse
      relationship between mRNA levels of asparagine synthetase and L-asparaginase
      sensitivity in the NCI-60. The concordance of pharmacogenomic findings at the DNA
      and mRNA levels strongly suggests further study of L-asparaginase for possible
      treatment of a low-synthetase subset of clinical ovarian cancers. The DNA copy
      number database presented here will enable other investigators to explore DNA
      transcript-drug relationships in their own domains of research focus.

PMID- 16648556
TI  - Gene expression profiling of whole-blood samples from women exposed to hormone
      replacement therapy.
AB  - The American Women's Health Initiative study published in July 2002 caused
      considerable concern among hormone replacement therapy (HRT) users and
      prescribers in many countries. This study is an exploratory research comparing
      the genome-wide expression profile in whole-blood samples according to HRT use.
      Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT
      users and 50 non-HRT users) born between 1943 and 1949 with normal to high body
      mass index and no other medication use were selected. After total RNA extraction,
      amplification, and labeling, the samples were hybridized together with a common
      reference (Universal human reference RNA, Stratagen) to Agilent Human 1A
      oligoarrays (G4110b, Agilent Technologies) containing 20,173 unique genes.
      Differentially expressed genes were used to build a classifier using the nearest
      shrunken centroid method (PAM). Then, we tested the significant changes in single
      genes by different methods like t test, Significance Analysis of Microarrays, and
      Bayesian ANOVA analysis. Results did not reveal any distinct gene list which
      predicted accurately HRT exposure (error rate, 0.40). Classifier performance
      slightly improved (error rate, 0.26) including only women who were using
      continuous combined HRT treatment. According to the small amplitude of expression
      alterations observed in whole blood, more quantitative technique and larger
      sample sizes will be needed to be able to investigate whether significant single
      genes are differentially expressed in HRT versus non-HRT users. Taken cautiously,
      significant enrichments in biological process of genes with small changes after
      HRT use were observed (e.g., receptor and transporter activities, immune
      response, frizzled signaling pathway, actin filament organization, and glycogen
      metabolism).

PMID- 16648557
TI  - A T3587G germ-line mutation of the MDR1 gene encodes a nonfunctional P
      glycoprotein.
AB  - The human multidrug resistance gene 1 (MDR1) encodes a plasma membrane P
      glycoprotein (P-gp) that functions as an efflux pump for various structurally
      unrelated anticancer agents. We have identified two nonsynonymous germ-line
      mutations of the MDR1 gene, C3583T MDR1 and T3587G MDR1, in peripheral blood cell
      samples from Japanese cancer patients. Two patients carried the C3583T MDR1
      allele that encodes H1195Y P-gp, whereas a further two carried T3587G MDR1 that
      encodes I1196S P-gp. Murine NIH3T3 cells were transfected with pCAL-MDR-IRES-ZEO
      constructs carrying either wild-type (WT), C3583T, or T3587G MDR1 cDNA and
      selected with zeocin. The resulting zeocin-resistant mixed populations of
      transfected cells were designated as 3T3/WT, 3T3/H1195Y, and 3T3/I1196S,
      respectively. The cell surface expression of I1196S P-gp in 3T3/I1196S cells
      could not be detected by fluorescence-activated cell sorting, although low
      expression of I1196S P-gp was found by Western blotting. H1195Y P-gp expression
      levels in 3T3/H1195Y cells were slightly lower than the corresponding WT P-gp
      levels in 3T3/WT cells. By immunoblotting analysis, both WT P-gp and H1195Y P-gp
      were detectable as a 145-kDa protein, whereas I1196S P-gp was visualized as a 140
      kDa protein. 3T3/I1196S cells did not show any drug resistance unlike 3T3/H1195Y
      cells. Moreover, a vanadate-trap assay showed that the I1196S P-gp species lacks
      ATP-binding activity. Taken together, we conclude from these data that T3587G
      MDR1 expresses a nonfunctional P-gp and this is therefore the first description
      of such a germ-line mutation. We contend that the T3587G MDR1 mutation may affect
      the pharmacokinetics of MDR1-related anticancer agents in patients carrying this
      allele.

PMID- 16648558
TI  - Effect of combined DNA repair inhibition and G2 checkpoint inhibition on cell
      cycle progression after DNA damage.
AB  - In response to DNA damage, cell survival can be enhanced by activation of DNA
      repair mechanisms and of checkpoints that delay cell cycle progression to allow
      more time for DNA repair. Inhibiting both responses with drugs might cause cancer
      cells to undergo cell division in the presence of lethal amounts of unrepaired
      DNA. However, we show that interfering with DNA repair via inhibition of DNA
      dependent protein kinase (DNA-PK) reduces the ability of checkpoint inhibitors to
      abrogate G2 arrest and their radiosensitizing activity. Cells exposed to the DNA
      PK inhibitor AMA37, DNA-PK-deficient cells, and nonhomologous end joining
      deficient cells all enter prolonged G2 arrest after exposure to ionizing
      radiation doses as low as 2 Gy. The checkpoint kinase Chk2 becomes rapidly and
      transiently overactivated, whereas Chk1 shows sustained overactivation that
      parallels the prolonged accumulation of cells in G2. Therefore, in irradiated
      cells, DNA repair inhibition elicits abnormally strong checkpoint signaling that
      causes essentially irreversible G2 arrest and strongly reduces the ability of
      checkpoint kinase inhibitors to overcome G2 arrest and radiosensitize cells.
      Variable levels of proteins controlling DNA repair have been documented in cancer
      cells. Therefore, these results have relevance to the development of DNA-PK
      inhibitors and G2 checkpoint inhibitors as experimental therapeutic approaches to
      enhance the selective killing of tumor cells by radiotherapy or DNA-damaging
      chemotherapeutic agents.

PMID- 16648559
TI  - Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering
      cell cycle kinetics and enhancing senescence.
AB  - We previously reported that methoxyamine (an inhibitor of base excision repair)
      potentiates iododeoxyuridine (IUdR)-induced radiosensitization in human tumor
      cells. In this study, we investigated the potential mechanisms of this enhanced
      cell death. Human colorectal carcinoma RKO cells were exposed to IUdR (3
      micromol/L) and/or methoxyamine (3 mmol/L) for 48 hours before ionizing radiation
      (5 Gy). We found that IUdR/methoxyamine altered cell cycle kinetics and led to an
      increased G1 population but a decreased S population before ionizing radiation.
      Immediately following ionizing radiation (up to 6 hours), IUdR/methoxyamine
      pretreated cells showed a stringent G1-S checkpoint but an insufficient G2-M
      checkpoint, whereas a prolonged G1 arrest, containing 2CG1 and 4CG1 cells, was
      found at later times up to 72 hours. Levels of cell cycle-specific markers [p21,
      p27, cyclin A, cyclin B1, and pcdc2(Y15)] and DNA damage signaling proteins
      [gammaH2AX, pChk1(S317), and pChk2(T68)] supported these altered cell cycle
      kinetics. Interestingly, we found that IUdR/methoxyamine pretreatment reduced
      ionizing radiation-induced apoptosis. Additionally, the extent of cell death
      through necrosis or autophagy seemed similar in all (IUdR +/- methoxyamine +
      ionizing radiation) treatment groups. However, a larger population of senescence
      activated beta-galactosidase-positive cells was seen in
      IUdR/methoxyamine/ionizing radiation-treated cells, which was correlated with the
      increased activation of the senescence factors p53 and pRb. These data indicate
      that IUdR/methoxyamine pretreatment enhanced the effects of ionizing radiation by
      causing a prolonged G1 cell cycle arrest and by promoting stress-induced
      premature senescence. Thus, senescence, a novel ionizing radiation-induced tumor
      suppression pathway, may be effectively targeted by IUdR/methoxyamine
      pretreatment, resulting in an improved therapeutic gain for ionizing radiation.

PMID- 16648560
TI  - Sensitizing hormone-refractory prostate cancer cells to drug treatment by
      targeting 14-3-3sigma.
AB  - Advanced and hormone-refractory prostate cancer has long been considered as a
      chemoresistant disease. Recently, it was found that 14-3-3sigma expression
      increases as prostate tumor progresses, and that 14-3-3sigma contributes
      significantly to drug resistance in breast cancers. We, thus, hypothesized that
      advanced and hormone-refractory prostate cancers may have an increased level of
      14-3-3sigma, which in turn may contribute to drug resistance in advanced and
      hormone-refractory prostate cancers. In this study, we tested this hypothesis and
      found that, indeed, the expression level of 14-3-3sigma in androgen-independent
      prostate cancer cell lines DU145, PC3, and CWR22RV are much higher than that in
      the androgen-dependent cell line LNCaP, and that the androgen-independent cells
      are more resistant to mitoxantrone and Adriamycin than the androgen-dependent
      cells. Depleting 14-3-3sigma expression in DU145 and CWR22RV by RNA interference
      significantly sensitized these cells to mitoxantrone and Adriamycin by abrogating
      G2-M checkpoint and increasing apoptosis, whereas restoring 14-3-3sigma
      expression in LNCaP cells enhanced drug resistance. We also showed that 14-3
      3sigma deficiency caused nuclear localization of Cdc2 and dephosphorylation of
      the Tyr15 residue upon DNA damage. Based on these studies, we propose that
      therapeutic intervention targeting 14-3-3sigma may be useful for sensitizing
      hormone-refractory prostate cancers to chemotherapy by both G2-M checkpoint
      abrogation and apoptosis enhancement.

PMID- 16648561
TI  - Mechanisms of selenium down-regulation of androgen receptor signaling in prostate
      cancer.
AB  - Prevention trials showed that selenium reduced prostate cancer incidence by 50%,
      establishing selenium as a promising chemopreventive agent for prostate cancer.
      Selenium inhibited human prostate cancer cell growth, blocked cell cycle
      progression at multiple transition points, and induced apoptotic cell death.
      Previous studies showed a novel mechanism of selenium anticancer action in which
      selenium markedly reduces androgen signaling and androgen receptor (AR)-mediated
      gene expression, including prostate-specific antigen (PSA), in human prostate
      cancer cells. The molecular mechanisms of selenium-mediated down-regulation of AR
      signaling are not clear. In this study, a systemic approach was taken to examine
      the modification of androgen signaling by selenium in human prostate cancer
      cells. In addition to reduced AR mRNA expression, selenium was found to initially
      increase the stability of AR mRNA within 6 hours while decreasing the stability
      of AR mRNA after 8 hours. Selenium increased AR protein degradation and reduced
      AR nuclear localization. Scatchard analysis indicated that selenium did not
      affect ligand binding to AR in LNCaP cells. Chromatin immunoprecipitation
      analyses showed that DHT increased the recruitment of AR and coactivators, such
      as SRC-1 and TIF-2, to the promoter of the PSA gene, and that recruitment was
      greatly diminished in the presence of 5 micromol/L selenium. On the other hand,
      selenium enhanced the recruitment of corepressors, such as SMRT, to the promoter
      of the PSA gene. Taken together, these results suggest that selenium disrupts AR
      signaling at multiple stages, including AR mRNA expression, mRNA stability,
      protein degradation, nuclear translocation, and recruitment of coregulators.

PMID- 16648562
TI  - Efficacy of a nitric oxide-releasing nonsteroidal anti-inflammatory drug and
      cytotoxic drugs in human colon cancer cell lines in vitro and xenografts.
AB  - We previously showed that NCX 4040 inhibits in vitro and in vivo tumor growth and
      induces apoptosis in human colon cancer cell lines. On the basis of these
      results, NCX 4040 antitumor activity in combination with 5-fluorouracil (5-FU) or
      oxaliplatin was evaluated in vitro and in vivo in human colon cancer models. The
      cytotoxicity of different NCX 4040 and 5-FU or oxaliplatin combination schemes
      was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr, and LRWZ) by
      the sulforhodamine B assay, and apoptosis was assessed by flow cytometry. NCX
      4040 and 5-FU combination was always additive in vitro regardless of the scheme
      used. Sequential NCX 4040-->oxaliplatin treatment produced a strong synergism in
      three cell lines, with a ratio index ranging from 3.7 to 4. The synergistic
      effect was accompanied by apoptosis induction (up to 40%). In the in vivo
      experiments, xenografted mice were treated with the sequential combination of NCX
      4040 and oxaliplatin, and apoptosis was evaluated immunohistochemically in
      excised tumors. Furthermore, in WiDr xenografts, this sequence caused a
      significantly higher reduction ( approximately 60%) in tumor growth compared with
      single-drug treatments and produced extensive apoptotic cell death (15.3%),
      significantly higher (P < 0.01) than that observed in untreated tumors (2.7%) or
      in tumors treated with NCX 4040 (5.1%) or oxaliplatin (5.7%) alone. These data
      show that NCX 4040 sensitizes colon cancer cell lines to the effect of antitumor
      drugs and suggests that their combination could be useful for the clinical
      management of colon cancer.

PMID- 16648563
TI  - Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA
      fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat
      cells.
AB  - Curcumin is a natural pigment that has been shown to induce cell death in many
      cancer cells; however, the death mode depends on the cell type and curcumin
      concentration. Here we show that, in Jurkat cells, 50 micromol/L curcumin
      severely lowers cell survival and induces initial stage of chromatin
      condensation. It also induces caspase-3, which is sufficient to cleave DNA
      fragmentation factor 45 [DFF45/inhibitor of caspase-activated DNase (ICAD)], the
      inhibitor of DFF40/CAD endonuclease. However, the release of DFF40/CAD from its
      inhibitor does not lead to oligonucleosomal DNA degradation in curcumin-treated
      cells. Moreover, curcumin treatment protects cells from UVC-induced
      oligonucleosomal DNA degradation. In biochemical experiments using recombinant
      DFF activated with caspase-3, we show that curcumin inhibits plasmid DNA and
      chromatin degradation although it does not prevent activation of DFF40/CAD
      endonuclease after its release from the inhibitor. Using DNA-binding assay, we
      show that curcumin does not disrupt the DNA-DFF40/CAD interaction. Instead,
      molecular modeling indicates that the inhibitory effect of curcumin on DFF40/CAD
      activity results from curcumin binding to the active center of DFF40/CAD
      endonuclease.

PMID- 16648564
TI  - Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases
      of cancer cells by a broccoli sprout extract.
AB  - We have previously shown that broccoli sprouts are a rich source of
      chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying
      enzymes and inhibit the development of mammary and skin tumors in rodents.
      However, the principal isothiocyanate present in broccoli sprout extracts,
      sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates
      apoptosis and blocks cell cycle progression. In this article, we show that an
      aqueous extract of broccoli sprouts potently inhibits the growth of human bladder
      carcinoma cells in culture and that this inhibition is almost exclusively due to
      the isothiocyanates. Isothiocyanates are present in broccoli sprouts as their
      glucosinolate precursors and blocking their conversion to isothiocyanates
      abolishes the antiproliferative activity of the extract. Moreover, the potency of
      isothiocyanates in the extract in inhibiting cancer cell growth was almost
      identical to that of synthetic sulforaphane, as judged by their IC50 values (6.6
      versus 6.8 micromol/L), suggesting that other isothiocyanates in the extract may
      be biologically similar to sulforaphane and that nonisothiocyanate substances in
      the extract may not interfere with the antiproliferative activity of the
      isothiocyanates. Further study showed that the isothiocyanate extract of broccoli
      sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in
      S and M phases. Cell cycle arrest was associated with down-regulation of Cdc25C
      and disruption of mitotic spindles. These data show that broccoli sprout
      isothiocyanate extract is a highly promising substance for cancer
      prevention/treatment and that its antiproliferative activity is exclusively
      derived from isothiocyanates.

PMID- 16648565
TI  - The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis
      factor-related apoptosis-inducing ligand.
AB  - Dietary flavonoid apigenin is expected to have preventive and therapeutic
      potential against malignant tumors. In this report, we show for the first time
      that apigenin markedly induces the expression of death receptor 5 (DR5) and
      synergistically acts with exogenous soluble recombinant human tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant
      tumor cells. TRAIL is a promising candidate for cancer therapeutics due to its
      ability to selectively induce apoptosis in cancer cells. The combined use of
      apigenin and TRAIL at suboptimal concentrations induces Bcl-2-interacting domain
      cleavage and the activation of caspases-8, -10, -9, and -3. Furthermore, human
      recombinant DR5/Fc chimera protein and caspase inhibitors dramatically inhibit
      apoptosis induced by the combination of apigenin and TRAIL. On the other hand,
      apigenin-mediated induction of DR5 expression is not observed in normal human
      peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal
      human peripheral blood mononuclear cells to TRAIL-induced apoptosis. These
      results suggest that this combined treatment with apigenin and TRAIL might be
      promising as a new therapy against malignant tumors.

PMID- 16648566
TI  - Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway.
AB  - Cisplatin resistance occurs, at least in part, through the function of the
      Fanconi anemia (FA)/BRCA pathway, a DNA-damage response pathway required for
      repair of cisplatin cross-links. In the current study, we designed a cell-based
      screening strategy to identify small-molecule inhibitors of the FA/BRCA pathway
      with the hypothesis that such molecules could restore sensitivity to platinum
      agents. We identified four inhibitors, including three protein kinase inhibitors
      (wortmannin, H-9, and alsterpaullone) and one natural compound (curcumin) that
      inhibit the FA/BRCA pathway. We show that curcumin, a compound that is generally
      regarded as safe, inhibits the monoubiquitination of the FANCD2 protein as
      predicted by the screen and consequently sensitizes ovarian and breast tumor cell
      lines to cisplatin through apoptotic cell death. We believe that this study shows
      an efficient, high-throughput method for identifying new compounds that may
      sensitize cancer cells to DNA-damaging chemotherapy.

PMID- 16648567
TI  - Potent antitumor activity of 10-methoxy-9-nitrocamptothecin.
AB  - The present data showed that 10-methoxy-9-nitrocamptothecin (MONCPT), a family of
      camptothecin analogues, possessed high antitumor activity in vitro and in vivo.
      Cytotoxicity assays showed that MONCPT was a potential and highly efficient
      antitumor compound with IC50 values of 0.1 to 500 nmol/L in nine tumor cell
      lines. The high cytotoxic potency of MONCPT was paralleled with its ability to
      increase the cellular accumulation of DNA damage. DNA relaxation assay also
      showed that MONCPT exerted high potency as a topoisomerase I inhibitor. Moreover,
      administration of MONCPT (5-20 mg/kg) for 15 to 17 days significantly inhibited
      tumor growth in human androgen-independent prostate tumor (PC3) and human non
      small cell lung tumor (A549) xenografts; the inhibition rates ranged from 29.6%
      to 98%. The cytotoxic effect of 1,000 nmol/L of MONCPT in PC3 cells was
      associated with causing an arrest in G0-G1 phase, whereas that of 10 and 100
      nmol/L MONCPT was relative to a persistent block in G2-M phase. Furthermore, down
      regulation of CDK2, CDK4, and cyclin D1 was observed in PC3 cells treated with
      1,000 nmol/L of MONCPT, whereas overexpression of CDK7, CDK1, and cyclin B1 was
      seen in PC3 cells treated with 10 and 100 nmol/L of MONCPT. These results
      suggested that cell cycle regulation might contribute to the anticancer
      properties of MONCPT and strongly support the further anticancer development of
      MONCPT.

PMID- 16648568
TI  - Mode of action of the chloroethylating and carbamoylating moieties of the prodrug
      cloretazine.
AB  - Cloretazine is an antitumor sulfonylhydrazine prodrug that generates both
      chloroethylating and carbamoylating species. The cytotoxic potency of these
      species was analyzed in L1210 leukemia cells using analogues with
      chloroethylating or carbamoylating function only. Clonogenic assays showed that
      the chloroethylating-only agent 1,2-bis(methylsulfonyl)-1-(2
      chloroethyl)hydrazine (90CE) produced marked differential cytotoxicity against
      wild-type and O6-alkylguanine-DNA alkyltransferase-transfected L1210 cells (LC10,
      1.4 versus 31 micromol/L), indicating that a large portion of the cytotoxicity
      was due to alkylation of DNA at the O-6 position of guanine. Consistent with the
      concept that O-6 chloroethylation of DNA guanine progresses to interstrand cross
      links, the comet assay, in which DNA cross-links were measured by a reduction in
      DNA migration induced by strand breaks, showed that cloretazine and 90CE, but not
      the carbamoylating-only agent 1,2-bis(methylsulfonyl)-1
      [(methylamino)carbonyl]hydrazine (101MDCE), produced DNA cross-links and that
      cloretazine caused more DNA cross-links than 90CE at equimolar concentrations.
      Cell cycle analyses showed that 90CE and 101MDCE at concentrations of 5 and 80
      micromol/L, respectively, produced similar degrees of G2-M arrest. 90CE produced
      selective inhibition of DNA synthesis after overnight incubation, whereas 101MDCE
      caused rapid and nonselective inhibition of RNA, DNA, and protein syntheses. Both
      90CE and 101MDCE induced phosphorylation of histone H2AX, albeit with distinct
      kinetics. These results indicate that (a) differential expression of O6
      alkylguanine-DNA alkyltransferase in tumor and host cells seems to be responsible
      for tumor selectivity exerted by cloretazine; (b) 101MDCE enhances DNA cross
      linking activity; and (c) 90CE induces cell death at concentrations lower than
      those causing alterations in the cell cycle and macromolecular syntheses.

PMID- 16648569
TI  - DNA adducts formed by a novel antitumor agent 11beta-dichloro in vitro and in
      vivo.
AB  - The multifunctional molecule 11beta-dichloro consists of a ligand for the
      androgen receptor linked to a bifunctional alkylating group, permitting it to
      create DNA adducts that bind the androgen receptor. We propose that binding of
      the androgen receptor to 11beta-DNA adducts acts to both shield damaged sites
      from repair and disrupt the expression of genes essential for growth and
      survival. We investigated the formation 11beta-DNA adducts in tumor xenograft and
      nontumor tissues in mice. Using [14C]-11beta-dichloro, we show that the molecule
      remains intact in blood and is widely distributed in mouse tissues after i.p.
      injection. Covalent 11beta-guanine adducts identified in DNA that had been
      allowed to react with 11beta-dichloro in vitro were also found in DNA isolated
      from cells in culture treated with 11beta-dichloro as well as in DNA isolated
      from liver and tumor tissues of mice treated with the compound. We used
      accelerator mass spectrometry to determine the levels of [14C]-11beta-DNA adducts
      in LNCaP cells treated in culture as well as in liver tissue and LNCaP xenograft
      tumors in treated mice. The level of DNA adducts in tumor tissue was found to be
      similar to that found in LNCaP cells in culture treated with 2.5 micromol/L
      11beta-dichloro. Our results indicate that 11beta-dichloro has sufficient
      stability to enter the circulation, penetrate tissues, and form DNA adducts that
      are capable of binding the androgen receptor in target tissues in vivo. These
      data suggest the involvement of our novel mechanisms in the antitumor effects of
      11beta-dichloro.

PMID- 16648570
TI  - Construction of a novel DNA decoy that inhibits the oncogenic beta-catenin/T-cell
      factor pathway.
AB  - The oncogenic beta-catenin/T-cell factor (TCF) signal is a common trigger
      inducing expressions of various cancer-related genes and is activated in various
      types of human malignancy. The aim of this study was to create an effective
      double-stranded DNA decoy that would interfere with endogenous TCF hyperactivity
      in tumor cells. We first established the TCF-activated model using nontumor human
      embryonic kidney 293 (HEK293) cells by introducing a beta-catenin cDNA. Based on
      a consensus TCF-binding sequence in the cyclin D1 and c-myc promoters, several
      double-stranded oligodeoxynucleotides were designed and tested for their ability
      to inhibit TCF activity in the HEK293 model. Among them, the 18-mer
      oligodeoxynucleotide stably formed double-stranded DNA and efficiently inhibited
      TCF activity. FITC-labeled oligodeoxynucleotide was efficiently incorporated into
      the nucleus at 6 hours and remained within cells for up to 72 to 96 hours. When
      compared with scrambled oligodeoxynucleotide, we found that the 18-mer TCF decoy
      significantly inhibited TCF activity and promoter activities of the downstream
      target genes, such as cyclin D1, c-myc, and matrix metalloproteinase 7 in HCT116
      colon cancer cells. Reverse transcription-PCR assays indicated that mRNA
      expression of these genes decreased with treatment of the TCF decoy.
      Proliferation assay showed that the TCF decoy significantly inhibited growth of
      HCT116 tumor cells, but not of nontumor HEK293 cells. Our data provide evidence
      that the TCF decoy reduced both TCF activity and transcriptional activation of
      downstream target genes. Thus, this TCF decoy is potentially an efficient and
      nontoxic molecular targeting therapy for controlling malignant properties of
      cancer cells.

PMID- 16648571
TI  - Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase
      inhibitor.
AB  - ABT-869 is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is
      a potent inhibitor of members of the vascular endothelial growth factor (VEGF)
      and platelet-derived growth factor (PDGF) receptor families (e.g., KDR IC50 = 4
      nmol/L) but has much less activity (IC50s > 1 micromol/L) against unrelated RTKs,
      soluble tyrosine kinases, or serine/threonine kinases. The inhibition profile of
      ABT-869 is evident in cellular assays of RTK phosphorylation (IC50 = 2, 4, and 7
      nmol/L for PDGFR-beta, KDR, and CSF-1R, respectively) and VEGF-stimulated
      proliferation (IC50 = 0.2 nmol/L for human endothelial cells). ABT-869 is not a
      general antiproliferative agent because, in most cancer cells, >1,000-fold higher
      concentrations of ABT-869 are required for inhibition of proliferation. However,
      ABT-869 exhibits potent antiproliferative and apoptotic effects on cancer cells
      whose proliferation is dependent on mutant kinases, such as FLT3. In vivo ABT-869
      is effective orally in the mechanism-based murine models of VEGF-induced uterine
      edema (ED50 = 0.5 mg/kg) and corneal angiogenesis (>50% inhibition, 15 mg/kg). In
      tumor growth studies, ABT-869 exhibits efficacy in human fibrosarcoma and breast,
      colon, and small cell lung carcinoma xenograft models (ED50 = 1.5-5 mg/kg, twice
      daily) and is also effective (>50% inhibition) in orthotopic breast and glioma
      models. Reduction in tumor size and tumor regression was observed in epidermoid
      carcinoma and leukemia xenograft models, respectively. In combination, ABT-869
      produced at least additive effects when given with cytotoxic therapies. Based on
      pharmacokinetic analysis from tumor growth studies, efficacy correlated more
      strongly with time over a threshold value (cellular KDR IC50 corrected for plasma
      protein binding = 0.08 microg/mL, >or=7 hours) than with plasma area under the
      curve or Cmax. These results support clinical assessment of ABT-869 as a
      therapeutic agent for cancer.

PMID- 16648572
TI  - Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms)
      tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase
      inhibitors.
AB  - The properties of several multitargeted receptor tyrosine kinase inhibitors have
      been studied for their inhibition of colony-stimulating factor-1 receptor (CSF
      1R) signaling. A structurally novel, multitargeted tyrosine kinase inhibitor (ABT
      869), imatinib (STI571), and four compounds currently in clinical development
      (AG013736, BAY 43-9006, CHIR258, and SU11248) were tested for inhibition of CSF
      1R signaling in both the enzymatic and cellular assays. ABT-869 showed potent CSF
      1R inhibition in both the enzyme and cell-based assays (IC50s < 20 nmol/L). In
      contrast to a previous report, we have found that imatinib has activity against
      human CSF-1R in both assays at submicromolar concentrations. In enzyme assays, we
      have found that the inhibition of CSF-1R by both ABT-869 and imatinib are
      competitive with ATP, with Ki values of 3 and 120 nmol/L, respectively. SU11248
      is a potent inhibitor of CSF-1R in the enzyme assay (IC50 = 7 nmol/L) and
      inhibits receptor phosphorylation in the cellular assay (IC50 = 61 nmol/L).
      AG013736 was also a potent inhibitor of CSF-1R in both assays (enzyme, IC50 = 16
      nmol/L; cellular, IC50 = 21 nmol/L), whereas BAY 43-9006 is less potent in the
      enzyme assay (IC50 = 107 nmol/L) than in the cellular system (IC50 = 20 nmol/L).
      In contrast, we found that CHIR258 had less activity in the cellular assay (IC50
      = 535 nmol/L) relative to its enzymatic potency (IC50 = 26 nmol/L). These results
      show the use of a cell-based assay to confirm the inhibitory activity of lead
      compounds and drug candidates, such as ABT-869, against the CSF-1R protein in
      situ.

PMID- 16648573
TI  - Enhancement of tumor thermal therapy using gold nanoparticle-assisted tumor
      necrosis factor-alpha delivery.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine with anticancer
      efficacy that can significantly enhance hyperthermic injury. However, TNF-alpha
      is systemically toxic, thereby creating a need for its selective tumor delivery.
      We used a newly developed nanoparticle delivery system consisting of 33-nm
      polyethylene glycol-coated colloidal gold nanoparticles (PT-cAu-TNF-alpha) with
      incorporated TNF-alpha payload (several hundred TNF-alpha molecules per
      nanoparticle) to maximize tumor damage and minimize systemic exposure to TNF
      alpha. SCK mammary carcinomas grown in A/J mice were treated with 125 or 250
      microg/kg PT-cAu-TNF-alpha alone or followed by local heating at 42.5 degrees C
      using a water bath for 60 minutes, 4 hours after nanoparticle injection.
      Increases in tumor growth delay were observed for both PT-cAu-TNF-alpha alone and
      heat alone, although the most dramatic effect was found in the combination
      treatment. Tumor blood flow was significantly suppressed 4 hours after an i.v.
      injection of free TNF-alpha or PT-cAu-TNF-alpha. Tumor perfusion, imaged by
      contrast enhanced ultrasonography, on days 1 and 5 after treatment revealed
      perfusion defects after the injection of PT-cAu-TNF-alpha alone and, in many
      regions, complete flow inhibition in tumors treated with combination treatment.
      The combination treatment of SCK tumors in vivo reduced the in vivo/in vitro
      tumor cell survival to 0.05% immediately following heating and to 0.005% at 18
      hours after heating, suggesting vascular damage-mediated tumor cell killing.
      Thermally induced tumor growth delay was enhanced by pretreatment with TNF-alpha
      coated gold nanoparticles when given i.v. at the proper dosage and timing.

PMID- 16648574
TI  - Targeted chemotherapy against intraperitoneally disseminated colon carcinoma
      using a cationized gelatin-conjugated HVJ envelope vector.
AB  - The hemagglutinating virus of Japan envelope (HVJ-E; Sendai virus) vector derived
      from inactivated HVJ particles can be used to deliver DNA, proteins, and drugs
      into cells both in vitro and in vivo. HVJ-E is capable of delivering bleomycin,
      an anticancer drug, to various cancer cell lines, thereby producing 300-fold
      greater cytotoxicity than administration of bleomycin alone. In a mouse model of
      peritoneally disseminated colon cancer, we injected HVJ-E containing the
      luciferase gene into the peritoneum. Unexpectedly, luciferase gene expression was
      not observed within the tumor deposits or any organs. However, when combined with
      cationized gelatin (CG), CG-HVJ-E produced a high level of luciferase gene
      expression primarily within the tumor deposits. Forty-eight hours after
      introducing colon cancer cells into the peritoneum of experimental mice, CG-HVJ-E
      with or without bleomycin was injected into the abdominal cavity. Following six
      injections of bleomycin-incorporated CG-HVJ-E, complete responses were observed
      in 40% of the mice examined. All of the mice that received either empty CG-HVJ-E
      or bleomycin alone died within 40 days of having cancer cells introduced into the
      peritoneum. When the mice with complete responses were rechallenged with colon
      cancer cells from the same cell line, no tumors developed. Thus, CG-HVJ-E may
      suppress peritoneal dissemination of cancer.

PMID- 16648575
TI  - Cytokines fused to antibodies and their combinations as therapeutic agents
      against different peritoneal HER2/neu expressing tumors.
AB  - We have previously generated antihuman HER2/neu-humanized IgG3 fused to
      interleukin-2 (IL-2), IL-12, or granulocyte macrophage colony-stimulating factor
      (GM-CSF) [monofunctional fusion proteins (mono-AbFP)] or fused to IL-2 and IL-12
      or IL-12 and GM-CSF [bifunctional fusion proteins (bi-AbFP)]. These AbFPs
      retained cytokine and antigen-binding activities. We have now further
      characterized the AbFPs and determined the heparin-binding activity of the fused
      cytokines, their ability to trigger IFN-gamma secretion and natural killer (NK)
      activation, and their direct antitumor efficacy. Flow cytometry revealed heparin
      binding activity in the AbFPs containing IL-12 and IL-2, although this activity
      seems to be decreased in the bi-AbFPs. However, both bi-AbFPs retained the
      capacity to stimulate IL-12-dependent IFN-gamma secretion in the NK cell line KY
      1, and IL-12/IL-2 bi-AbFP induced NK activity in splenocytes. The antitumor
      effectiveness of bi-AbFPs and mono-AbFP combinations was studied in mice
      challenged i.p. with three different human HER2/neu murine syngeneic models
      (D2F2/E2, CT26-HER2/neu, and MC38-HER2/neu). Although a significant variability
      in the profile of antitumor response was observed in the different tumor models,
      the combination of IL-12 and GM-CSF mono-AbFPs protected 100% of D2F2/E2
      challenged and 75% of CT26-HER2/neu-challenged mice. In contrast, bi-AbFPs
      protected less than the combination of mono-AbFPs and, in some models, even less
      than mono-AbFPs alone. However, in all cases, most of long-term survivors showed
      protection after s.c. rechallenge with the tumors and later with the parental
      tumors not expressing HER2/neu. These results show that, although the pattern of
      protection is tumor model dependent, treatments with AbFPs can effectively
      generate high levels of protection against peritoneal tumors expressing HER2/neu,
      which may be relevant in patients with primary or metastatic peritoneal
      carcinomatosis that may be observed in ovarian, colon, stomach, bladder, lung,
      and breast cancers.

PMID- 16648576
TI  - Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4
      complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null
      mice.
AB  - The low efficiency of conventional therapies in achieving long-term survival of
      patients with lung cancer calls for development of novel treatment options.
      Although several genes have been investigated for their antitumor activities
      through gene delivery, problems surrounding the methods used, such as efficiency,
      specificity, and toxicity, hinder application of such therapies in clinical
      settings. Aerosol gene delivery as nonviral and noninvasive method for gene
      therapy may provide an alternative for a safer and more effective treatment for
      lung cancer. In this study, imidazole ring-containing urocanic acid-modified
      chitosan (UAC) designed in previous study was used as a gene carrier. The
      efficiency of UAC carrier in lungs was confirmed, and the potential effects of
      the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major
      pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol
      containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model
      mice through the nose-only inhalation system developed by our group. Delivered
      UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell
      proliferation, and efficiently suppressed pathways important for tumor
      angiogenesis. In summary, results obtained by Western blot analysis,
      immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end
      labeling assay suggest that our aerosol gene delivery technique is compatible
      with in vivo gene delivery and can be applied as a noninvasive gene therapy.

PMID- 16648577
TI  - AMP-activated protein kinase protects against anti-epidermal growth factor
      receptor-Pseudomonas exotoxin A immunotoxin-induced MA11 breast cancer cell
      death.
AB  - We have shown previously that our 425.3PE immunotoxin inhibits protein synthesis
      and induces apoptosis in human breast cancer cells. In attempts to further
      elucidate the intracellular pathways implicated in its cellular effects, we found
      that the immunotoxin induced an initial stress response, which rapidly caused an
      imbalance in the cellular energy status with an increase in reactive oxygen
      species. The AMP-activated protein kinase (AMPK), a sensor of increased cellular
      AMP/ATP ratio, was activated by 425.3PE. An immunotoxin-induced activation of c
      Jun NH2-terminal kinase (JNK) preceded and overlapped caspase-mediated cleavage
      of the alpha-subunit of AMPK in a time- and dose-dependent manner. The JNK
      activation occurred already at a dose level too low to induce any detectable
      changes in the apoptotic machinery or protein synthesis. In contrast,
      cycloheximide, even at a concentration causing a 90% inhibition of protein
      synthesis, did neither affect the ATP level nor activate JNK and AMPK.
      Pretreatment of the cells with the specific AMPK inhibitor compound C and JNK
      inhibitor SP600125 blocked activation of AMPK and JNK, respectively, and
      subsequently sensitized the cells to 425.3PE-induced cell death. Whereas the
      antioxidant N-acetyl-l-cysteine blocked the generation of reactive oxygen species
      and activation of JNK and AMPK, it did not block immunotoxin-induced apoptosis.
      Together, the results show that 425.3PE induces several parallel signaling
      events, observed initially as an early activation of survival pathways,
      protecting the cells against the toxic effects of the immunotoxin, followed by
      subsequent apoptosis induction and protein synthesis inhibition. Conceivably,
      therapeutic manipulation of the signaling intermediates AMPK and JNK might
      provide a means to maximize the anticancer effects of the 425.3 immunotoxin.

PMID- 16648578
TI  - Organ-specific expression profiles of rat mammary gland, liver, and lung tissues
      treated with targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide.
AB  - A rexinoid, targretin, and two retinoids, 9-cis retinoic acid (9cRA) and 4
      hydroxyphenylretinamide (4HPR), were examined for their effects on gene
      expression in rat mammary gland, liver, and lung tissues. The chemopreventive
      effects of these agents have largely been attributed to their ability to interact
      with retinoic acid receptors (RAR) and/or retinoid X receptors (RXR). Targretin
      interacts with the RXR receptors. 9cRA interacts with both the RAR and RXR
      receptors, whereas 4HPR has a moderate affinity primarily for RAR gamma. Based on
      previous studies on mammary chemoprevention, targretin (150 mg/kg diet), 9cRA
      (100 mg/kg diet), and 4HPR (782 mg/kg diet), were administered to rats
      continually in their diet for 7 days. Tissue- and agent-specific expression
      differences were determined by comparing tissues from treated rats with those
      from rats given a control diet. There were significantly more changes associated
      with targretin than 9cRA or 4HPR. Only a limited number of expression changes
      were found with 4HPR treatment. For each organ, targretin- and 9cRA-treated
      tissues clustered closely together, whereas 4HPR-treated tissues clustered with
      the tissues from the control diet group. In contrast to 9cRA treatment, targretin
      treatment altered genes that involved fatty acid metabolism and modulation of
      various cytochromes P450 in the liver, clearly demonstrating the very disparate
      nature of these two retinoids. These expression signatures could provide useful
      pharmacodynamic biomarkers for retinoid treatment and chemoprevention.

PMID- 16648579
TI  - Effects of the farnesyl transferase inhibitor R115777 (Zarnestra) on mammary
      carcinogenesis: prevention, therapy, and role of HaRas mutations.
AB  - The ability of the farnesyl transferase inhibitor R115777 to act as a cancer
      therapeutic/preventive agent and to modulate proliferation/apoptosis markers was
      determined in the methylnitrosourea-induced model of mammary carcinogenesis.
      Female Sprague-Dawley rats were given methylnitrosourea at 50 days of age. In the
      prevention study, R115777 (5, 16, or 50 mg/kg body weight/d), beginning 5 days
      after methylnitrosourea treatment, decreased the formation of mammary cancers by
      6%, 42%, and 75%, respectively. Approximately 50% of the mammary cancers that
      developed had HaRas mutations. Only 1 of 15 tumors that grew out in the presence
      of R115777 (16 or 50 mg/kg body weight/d) had a HaRas mutation. In the
      therapeutic study, a surgical biopsy of a mammary cancer was done to determine
      HaRas status, and growth of the cancer was then followed during treatment of the
      rat with R115777. Virtually every cancer with a HaRas mutation underwent complete
      regression within 3 weeks, whereas tumors without a HaRas mutation had variable
      responses to the inhibitor. Both of these studies implied a high sensitivity of
      tumors with HaRas mutations to the effects of R115777. In order to understand the
      preferential susceptibility of tumors with HaRas mutations, rats with a palpable
      cancer were treated with R115777 for a period of 36 or 96 hours prior to
      sacrifice, and the proliferation and apoptosis levels in the cancers were
      determined. The proliferative index was significantly (>85%) decreased in all
      mammary cancers with HaRas mutations, whereas variable responses were observed in
      cancers without HaRas mutations. Apoptosis was also measured and a 5-fold
      increase was observed in HaRas mutant tumors, again with varying responses in the
      HaRas wild-type cancers. Thus, R115777 was active in the prevention and therapy
      of these chemically induced mammary cancers, but was strikingly more effective in
      cancers with HaRas mutations.

PMID- 16648580
TI  - Diarylureas are small-molecule inhibitors of insulin-like growth factor I
      receptor signaling and breast cancer cell growth.
AB  - In breast and certain other cancers, receptor tyrosine kinases, including the
      insulin-like growth factor I receptor (IGF-IR), play an important role in
      promoting the oncogenic process. The IGF-IR is therefore an important target for
      developing new anti-breast cancer therapies. An initial screening of a chemical
      library against the IGF-IR in breast cancer cells identified a diaryl urea
      compound as a potent inhibitor of IGF-IR signaling. This class of compounds has
      not been studied as inhibitors of the IGF-IR. We studied the effectiveness of one
      diaryl urea compound, PQ401, at antagonizing IGF-IR signaling and inhibiting
      breast cancer cell growth in culture and in vivo. PQ401 inhibited
      autophosphorylation of the IGF-IR in cultured human MCF-7 cells with an IC50 of
      12 micromol/L and autophosphorylation of the isolated kinase domain of the IGF-IR
      with an IC50 <1 micromol/L. In addition, PQ401 inhibited the growth of cultured
      breast cancer cells in serum at 10 micromol/L. PQ401 was even more effective at
      inhibiting IGF-I-stimulated growth of MCF-7 cells (IC50, 6 micromol/L). Treatment
      of MCF-7 cells with PQ401 was associated with a decrease in IGF-I-mediated
      signaling through the Akt antiapoptotic pathway. Twenty-four hours of treatment
      with 15 micromol/L PQ401 induced caspase-mediated apoptosis. In vivo, treatment
      with PQ401 (i.p. injection thrice a week) reduced the growth rate of MCNeuA cells
      implanted into mice. These studies indicate that diaryl urea compounds are
      potential new agents to test in the treatment of breast and other IGF-I-sensitive
      cancers.

PMID- 16648581
TI  - Divergence with gene flow in Anopheles funestus from the Sudan Savanna of Burkina
      Faso, West Africa.
AB  - Anopheles funestus is a major vector of malaria across Africa. Understanding its
      complex and nonequilibrium population genetic structure is an important challenge
      that must be overcome before vector populations can be successfully perturbed for
      malaria control. Here we examine the role of chromosomal inversions in
      structuring genetic variation and facilitating divergence in Burkina Faso, West
      Africa, where two incipient species (chromosomal forms) of A. funestus, defined
      principally by rearrangements of chromosome 3R, have been hypothesized. Sampling
      across an approximately 300-km east-west transect largely contained within the
      Sudan-Savanna ecoclimatic zone, we analyzed chromosomal inversions, 16
      microsatellite loci distributed genomewide, and 834 bp of the mtDNA ND5 gene.
      Both molecular markers revealed high genetic diversity, nearly all of which was
      accounted for by within-population differences among individuals, owing to recent
      population expansion. Across the study area there was no correlation between
      genetic and geographic distance. Significant genetic differentiation found
      between chromosomal forms on the basis of microsatellites was not genomewide but
      could be explained by chromosome 3R alone on the basis of loci inside and near
      inversions. These data are not compatible with complete reproductive isolation
      but are consistent with differential introgression and sympatric divergence
      between the chromosomal forms, facilitated by chromosome 3R inversions.

PMID- 16648582
TI  - Ribosomal RNA gene silencing in interpopulation hybrids of Tigriopus
      californicus: nucleolar dominance in the absence of intergenic spacer subrepeats.
AB  - A common feature of interspecific animal and plant hybrids is the uniparental
      silencing of ribosomal RNA gene transcription, or nucleolar dominance. A leading
      explanation for the genetic basis of nucleolar dominance in animal hybrids is the
      enhancer-imbalance model. The model proposes that limiting transcription factors
      are titrated by a greater number of enhancer-bearing subrepeat elements in the
      intergenic spacer (IGS) of the dominant cluster of genes. The importance of
      subrepeats for nucleolar dominance has repeatedly been supported in competition
      assays between Xenopus laevis and X. borealis minigene constructs injected into
      oocytes. However, a more general test of the importance of IGS subrepeats for
      nuclear dominance in vivo has not been conducted. In this report, rRNA gene
      expression was examined in interpopulation hybrids of the marine copepod
      Tigriopus californicus. This species offers a rare opportunity to test the role
      of IGS subrepeats in nucleolar dominance because the internal subrepeat
      structure, found in the IGS of virtually all animal and plant species, is absent
      in T. californicus. Our results clearly establish that nucleolar dominance occurs
      in F1 and F2 interpopulation hybrids of this species. In the F2 generation,
      nucleolar dominance appears to break down in some hybrids in a fashion that is
      inconsistent with a transcription factor titration model. These results are
      significant because they indicate that nucleolar dominance can be established and
      maintained without enhancer-bearing repeat elements in the IGS. This challenges
      the generality of the enhancer-imbalance model for nucleolar dominance and
      suggests that dominance of rRNA transcription in animals may be determined by
      epigenetic factors as has been established in plants.

PMID- 16648583
TI  - The Saccharomyces cerevisiae 14-3-3 proteins are required for the G1/S
      transition, actin cytoskeleton organization and cell wall integrity.
AB  - 14-3-3 proteins are highly conserved polypeptides that participate in many
      biological processes by binding phosphorylated target proteins. The Saccharomyces
      cerevisiae BMH1 and BMH2 genes, whose concomitant deletion is lethal, encode two
      functionally redundant 14-3-3 isoforms. To gain insights into the essential
      function(s) shared by these proteins, we searched for high-dosage suppressors of
      the growth defects of temperature-sensitive bmh mutants. Both the protein kinase
      C1 (Pkc1) and its upstream regulators Wsc2 and Mid2 were found to act as high
      dosage suppressors of bmh mutants' temperature sensitivity, indicating a
      functional interaction between 14-3-3 and Pkc1. Consistent with a role of 14-3-3
      proteins in Pkc1-dependent cellular processes, shift to the restrictive
      temperature of bmh mutants severely impaired initiation of DNA replication,
      polarization of the actin cytoskeleton, and budding, as well as cell wall
      integrity. Because Pkc1 acts in concert with the Swi4-Swi6 (SBF) transcriptional
      activator to control all these processes, the defective G(1)/S transition of bmh
      mutants might be linked to impaired SBF activity. Indeed, the levels of the G(1)
      cyclin CLN2 transcripts, which are positively regulated by SBF, were dramatically
      reduced in bmh mutants. Remarkably, budding and DNA replication defects of bmh
      mutants were suppressed by CLN2 expression from an SBF-independent promoter,
      suggesting that 14-3-3 proteins might contribute to regulating the late G(1)
      transcriptional program.

PMID- 16648584
TI  - A genetic suppressor of two dominant temperature-sensitive lethal proteasome
      mutants of Drosophila melanogaster is itself a mutated proteasome subunit gene.
AB  - Two dominant temperature-sensitive (DTS) lethal mutants of Drosophila
      melanogaster are Pros26(1) and Prosbeta2(1), previously known as DTS5 and DTS7.
      Heterozygotes for either mutant die as pupae when raised at 29 degrees , but are
      normally viable and fertile at 25 degrees . Previous studies have identified
      these as missense mutations in the genes encoding the beta6 and beta2 subunits of
      the 20S proteasome, respectively. In an effort to isolate additional proteasome
      related mutants a screen for dominant suppressors of Pros26(1) was carried out,
      resulting in the identification of Pros25(SuDTS) [originally called Su(DTS)], a
      missense mutation in the gene encoding the 20S proteasome alpha2 subunit.
      Pros25(SuDTS) acts in a dominant manner to rescue both Pros26(1) and Prosbeta2(1)
      from their DTS lethal phenotypes. Using an in vivo protein degradation assay it
      was shown that this suppression occurs by counteracting the dominant-negative
      effect of the DTS mutant on proteasome activity. Pros25(SuDTS) is a recessive
      polyphasic lethal at ambient temperatures. The effects of these mutants on larval
      neuroblast mitosis were also examined. While Prosbeta2(1) shows a modest increase
      in the number of defective mitotic figures, there were no defects seen with the
      other two mutants, other than slightly reduced mitotic indexes.

PMID- 16648586
TI  - Evolution and expression of homeologous loci in Tragopogon miscellus
      (Asteraceae), a recent and reciprocally formed allopolyploid.
AB  - On both recent and ancient time scales, polyploidy (genome doubling) has been a
      significant evolutionary force in plants. Here, we examined multiple individuals
      from reciprocally formed populations of Tragopogon miscellus, an allotetraploid
      that formed repeatedly within the last 80 years from the diploids T. dubius and
      T. pratensis. Using cDNA-AFLPs followed by genomic and cDNA cleaved amplified
      polymorphic sequence (CAPS) analyses, we found differences in the evolution and
      expression of homeologous loci in T. miscellus. Fragment variation within T.
      miscellus, possibly attributable to reciprocal formation, comprised 0.6% of the
      cDNA-AFLP bands. Genomic and cDNA CAPS analyses of 10 candidate genes revealed
      that only one "transcript-derived fragment" (TDF44) showed differential
      expression of parental homeologs in T. miscellus; the T. pratensis homeolog was
      preferentially expressed by most polyploids in both populations. Most of the cDNA
      AFLP polymorphisms apparently resulted from loss of parental fragments in the
      polyploids. Importantly, changes at the genomic level have occurred
      stochastically among individuals within the independently formed populations.
      Synthetic F(1) hybrids between putative diploid progenitors are additive of their
      parental genomes, suggesting that polyploidization rather than hybridization
      induces genomic changes in Tragopogon.

PMID- 16648585
TI  - Glial and neuronal functions of the Drosophila homolog of the human SWI/SNF gene
      ATR-X (DATR-X) and the jing zinc-finger gene specify the lateral positioning of
      longitudinal glia and axons.
AB  - Neuronal-glial communication is essential for constructing the orthogonal axon
      scaffold in the developing Drosophila central nervous system (CNS). Longitudinal
      glia (LG) guide extending commissural and longitudinal axons while pioneer and
      commissural neurons maintain glial survival and positioning. However, the
      transcriptional regulatory mechanisms controlling these processes are not known.
      Previous studies showed that the midline function of the jing C2H2-type zinc
      finger transcription factor was only partially required for axon scaffold
      formation in the Drosophila CNS. We therefore screened for gain-of-function
      enhancers of jing gain of function in the eye and identified the Drosophila
      homolog of the disease gene of human alpha-thalassemia/mental retardation X
      linked (ATR-X) as well as other genes with potential roles in gene expression,
      translation, synaptic transmission, and cell cycle. jing and DATR-X reporter
      genes are expressed in both CNS neurons and glia, including the LG. Coexpression
      of jing and DATR-X in embryonic neurons synergistically affects longitudinal
      connective formation. During embryogenesis, jing and DATR-X have autonomous and
      nonautonomous roles in the lateral positioning of LG, neurons, and longitudinal
      axons as shown by cell-specific knockdown of gene expression. jing and DATR-X are
      also required autonomously for glial survival. jing and DATR-X mutations show
      synergistic effects during longitudinal axon formation suggesting that they are
      functionally related. These observations support a model in which downstream gene
      expression controlled by a potential DATR-X-Jing complex facilitates cellular
      positioning and axon guidance, ultimately allowing for proper connectivity in the
      developing Drosophila CNS.

PMID- 16648587
TI  - Metabolic disruption in Drosophila bang-sensitive seizure mutants.
AB  - We examined a number of Drosophila mutants with increased susceptibility to
      seizures following mechanical or electrical stimulation to better understand the
      underlying factors that predispose neurons to aberrant activity. Several
      mutations in this class have been molecularly identified and suggest metabolic
      disruption as a possible source for increased seizure susceptibility. We mapped
      the bang-sensitive seizure mutation knockdown (kdn) to cytological position 5F3
      and identified citrate synthase as the affected gene. These results further
      support a role for mitochondrial metabolism in controlling neuronal activity and
      seizure susceptibility. Biochemical analysis in bang-sensitive mutants revealed
      reductions in ATP levels consistent with disruption of mitochondrial energy
      production in these mutants. Electrophysiological analysis of mutants affecting
      mitochondrial proteins revealed an increased likelihood for a specific pattern of
      seizure activity. Our data implicate cellular metabolism in regulating seizure
      susceptibility and suggest that differential sensitivity of neuronal subtypes to
      metabolic changes underlies distinct types of seizure activity.

PMID- 16648588
TI  - Multiple quantitative trait loci modify cochlear hair cell degeneration in the
      Beethoven (Tmc1Bth) mouse model of progressive hearing loss DFNA36.
AB  - Dominant mutations of transmembrane channel-like gene 1 (TMC1) cause progressive
      sensorineural hearing loss in humans and Beethoven (Tmc1Bth/+) mice. Here we show
      that Tmc1Bth/+ mice on a C3HeB/FeJ strain background have selective degeneration
      of inner hair cells while outer hair cells remain structurally and functionally
      intact. Inner hair cells primarily function as afferent sensory cells, whereas
      outer hair cells are electromotile amplifiers of auditory stimuli that can be
      functionally assessed by distortion product otoacoustic emission (DPOAE)
      analysis. When C3H-Tmc1Bth/Bth is crossed with either C57BL/6J or DBA/2J wild
      type mice, F1 hybrid Tmc1Bth/+ progeny have increased hearing loss associated
      with increased degeneration of outer hair cells and diminution of DPOAE
      amplitudes but no difference in degeneration of inner hair cells. We mapped at
      least one quantitative trait locus (QTL), Tmc1m1, for DPOAE amplitude on
      chromosome 2 in [(C/B)F1xC]N2-Tmc1Bth/+ backcross progeny, and three other QTL on
      chromosomes 11 (Tmc1m2), 12 (Tmc1m3), and 5 (Tmc1m4) in [(C/D)F1xC]N2-Tmc1Bth/+
      progeny. The polygenic basis of outer hair cell degeneration in Beethoven mice
      provides a model system for the dissection of common, complex hearing loss
      phenotypes, such as presbycusis, that involve outer hair cell degeneration in
      humans.

PMID- 16648589
TI  - Unusual DNA structures associated with germline genetic activity in
      Caenorhabditis elegans.
AB  - We describe a surprising long-range periodicity that underlies a substantial
      fraction of C. elegans genomic sequence. Extended segments (up to several hundred
      nucleotides) of the C. elegans genome show a strong bias toward occurrence of
      AA/TT dinucleotides along one face of the helix while little or no such
      constraint is evident on the opposite helical face. Segments with this
      characteristic periodicity are highly overrepresented in intron sequences and are
      associated with a large fraction of genes with known germline expression in C.
      elegans. In addition to altering the path and flexibility of DNA in vitro,
      sequences of this character have been shown by others to constrain
      DNA::nucleosome interactions, potentially producing a structure that could resist
      the assembly of highly ordered (phased) nucleosome arrays that have been proposed
      as a precursor to heterochromatin. We propose a number of ways that the periodic
      occurrence of An/Tn clusters could reflect evolution and function of genes that
      express in the germ cell lineage of C. elegans.

PMID- 16648590
TI  - Centromere locations and associated chromosome rearrangements in Arabidopsis
      lyrata and A. thaliana.
AB  - We analyzed linkage and chromosomal positions of genes in A. lyrata ssp. petraea
      that are located near the centromere (CEN) regions of A. thaliana, using at least
      two genes from the short and long arms of each chromosome. In our map, genes from
      all 10 A. thaliana chromosome arms are also tightly linked in A. lyrata. Genes
      from the regions on the two sides of CEN5 have distant map localizations in A.
      lyrata (genes on the A. thaliana short-arm genes are on linkage group AL6, and
      long-arm genes are on AL7), but genes from the other four A. thaliana centromere
      regions remain closely linked in A. lyrata. The observation of complete linkage
      between short- and long-arm centromere genes, but not between genes in other
      genome regions that are separated by similar physical distances, suggests that
      crossing-over frequencies near the A. lyrata ssp. petraea centromere regions are
      low, as in A. thaliana. Thus, the centromere positions appear to be conserved
      between A. thaliana and A. lyrata, even though three centromeres have been lost
      in A. thaliana, and the core satellite sequences in the two species are very
      different. We can now definitively identify the three centromeres that were
      eliminated in the fusions that formed the A. thaliana chromosomes. However, we
      cannot tell whether genes were lost along with these centromeres, because such
      genes are absent from the A. thaliana genome, which is the sole source of markers
      for our mapping.

PMID- 16648591
TI  - Genetic map-based analysis of genome structure in the homosporous fern
      Ceratopteris richardii.
AB  - Homosporous ferns have extremely high chromosome numbers relative to flowering
      plants, but the species with the lowest chromosome numbers show gene expression
      patterns typical of diploid organisms, suggesting that they may be diploidized
      ancient polyploids. To investigate the role of polyploidy in fern genome
      evolution, and to provide permanent genetic resources for this neglected group,
      we constructed a high-resolution genetic linkage map of the homosporous fern
      model species, Ceratopteris richardii (n = 39). Linkage map construction employed
      488 doubled haploid lines (DHLs) that were genotyped for 368 RFLP, 358 AFLP, and
      3 isozyme markers. Forty-one linkage groups were recovered, with average spacing
      between markers of 3.18 cM. Most loci (approximately 76%) are duplicated and most
      duplicates occur on different linkage groups, indicating that as in other
      eukaryotic genomes, gene duplication plays a prominent role in shaping the
      architecture of fern genomes. Although past polyploidization is a potential
      mechanism for the observed abundance of gene duplicates, a wide range in the
      number of gene duplicates as well as the absence of large syntenic regions
      consisting of duplicated gene copies implies that small-scale duplications may be
      the primary mode of gene duplication in C. richardii. Alternatively, evidence of
      past polyploidization(s) may be masked by extensive chromosomal rearrangements as
      well as smaller-scale duplications and deletions following polyploidization(s).

PMID- 16648592
TI  - Epidermal growth factor receptor and transforming growth factor-beta signaling
      contributes to variation for wing shape in Drosophila melanogaster.
AB  - Wing development in Drosophila is a common model system for the dissection of
      genetic networks and their roles during development. In particular, the RTK and
      TGF-beta regulatory networks appear to be involved with numerous aspects of wing
      development, including patterning, cell determination, growth, proliferation, and
      survival in the developing imaginal wing disc. However, little is known as to how
      subtle changes in the function of these genes may contribute to quantitative
      variation for wing shape, per se. In this study 50 insertional mutations,
      representing 43 loci in the RTK, Hedgehog, TGF-beta pathways, and their
      genetically interacting factors were used to study the role of these networks on
      wing shape. To concurrently examine how genetic background modulates the effects
      of the mutation, each insertion was introgressed into two wild-type genetic
      backgrounds. Using geometric morphometric methods, it is shown that the majority
      of these mutations have profound effects on shape but not size of the wing when
      measured as heterozygotes. To examine the relationships between how each mutation
      affects wing shape hierarchical clustering was used. Unlike previous observations
      of environmental canalization, these mutations did not generally increase within
      line variation relative to their wild-type counterparts. These results provide an
      entry point into the genetics of wing shape and are discussed within the
      framework of the dissection of complex phenotypes.

PMID- 16648593
TI  - Genomic-assisted prediction of genetic value with semiparametric procedures.
AB  - Semiparametric procedures for prediction of total genetic value for quantitative
      traits, which make use of phenotypic and genomic data simultaneously, are
      presented. The methods focus on the treatment of massive information provided by,
      e.g., single-nucleotide polymorphisms. It is argued that standard parametric
      methods for quantitative genetic analysis cannot handle the multiplicity of
      potential interactions arising in models with, e.g., hundreds of thousands of
      markers, and that most of the assumptions required for an orthogonal
      decomposition of variance are violated in artificial and natural populations.
      This makes nonparametric procedures attractive. Kernel regression and reproducing
      kernel Hilbert spaces regression procedures are embedded into standard mixed
      effects linear models, retaining additive genetic effects under multivariate
      normality for operational reasons. Inferential procedures are presented, and some
      extensions are suggested. An example is presented, illustrating the potential of
      the methodology. Implementations can be carried out after modification of
      standard software developed by animal breeders for likelihood-based or Bayesian
      analysis.

PMID- 16648594
TI  - Behavioral assessment and characteristics of patients seeking bariatric surgery.

PMID- 16648595
TI  - Behavioral assessment of candidates for bariatric surgery: a patient-oriented
      approach.
AB  - This paper discusses the behavioral evaluation of patients who seek bariatric
      surgery and the psychosocial complications most frequently observed in these
      individuals. The effects of such complications on surgical outcome are briefly
      examined, as is the challenge of predicting therapeutic response on the basis of
      preoperative variables. The paper concludes with a description of the goals and
      methods of a behavioral assessment used at the University of Pennsylvania. This
      evaluation includes the use of the Weight and Lifestyle Inventory, a
      questionnaire that guides our interview with patients.

PMID- 16648596
TI  - A comparison of weight histories in women with class III vs. class I-II obesity.
AB  - OBJECTIVE: To describe the weight histories of women with extreme or class III
      obesity (BMI >or= 40 kg/m(2)) in comparison with a sample of women with class I
      II obesity (BMI < 40 kg/m(2)) and to provide reliability data for a clinical
      instrument that assesses weight history. RESEARCH METHODS AND PROCEDURES: Female
      patients (N = 149) with extreme obesity seeking bariatric surgery and 90 class I
      II obese women seeking behavioral treatment completed the Weight and Lifestyle
      Inventory (WALI), a self-report instrument that assesses age of onset of obesity,
      maximum weight at different ages, family weight history, and weight changes
      related to pregnancy. Test-retest reliability data were obtained by administering
      the WALI to a subsample (n = 58) of class I-II obese participants at their
      initial visit and at another pretreatment visit 1 to 2 weeks later. RESULTS:
      Patients with extreme obesity had a significantly younger age of onset of
      obesity, were significantly heavier at all age ranges, reported significantly
      more weight gain with their first pregnancy, and had significantly heavier
      parents and siblings as compared with less obese patients. There were no
      significant differences between groups with respect to weight gain during second
      pregnancies or postpartum weight retention. Robust test-retest correlations were
      obtained for the weight history items on the WALI. DISCUSSION: Patients with
      extreme obesity report more indicators of a genetic predisposition to obesity as
      compared with less obese patients. The WALI appears to be a reliable instrument
      for the assessment of weight history in obese patients.

PMID- 16648597
TI  - Previous weight loss experiences of bariatric surgery candidates: how much have
      patients dieted prior to surgery?
AB  - OBJECTIVE: To describe the dieting histories of bariatric surgery candidates.
      RESEARCH METHODS AND PROCEDURES: One hundred seventy-seven individuals with
      extreme obesity who sought bariatric surgery completed the Weight and Lifestyle
      Inventory, a self-report instrument that assesses several variables, including
      weight and dieting history. Patients' dieting histories were further explored
      with an aided recall during a preoperative behavioral/psychological evaluation
      performed by a mental health professional. RESULTS: Participants who completed
      the Weight and Lifestyle Inventory reported an average of 4.7 +/- 2.9 successful
      dieting attempts, defined as those that resulted in a loss of 10 lbs (4.5 kg) or
      more. These individuals reported a mean total lifetime weight loss of 61.1 +/-
      41.3 kg. Despite these efforts, their weight increased from 89.4 +/- 27.4 kg at
      the time of their first diet (age 21.2 +/- 10.1 years) to 144.5 +/- 30.8 kg at
      the time they underwent their behavioral/psychological evaluation (age 43.0 +/-
      11.0 years). Results of the aided recall revealed that participants had made
      numerous other efforts to lose weight that were unsuccessful. Self-directed diets
      and commercial programs were used more frequently. DISCUSSION: Individuals who
      sought bariatric surgery reported an extensive history of dieting, beginning in
      adolescence, that was not successful in halting progressive weight gain. Thus,
      the recommendation often made by insurance companies that patients delay surgery
      to attempt more conservative treatment options may be unwarranted, particularly
      in the presence of significant obesity-related comorbidities. Weight loss
      histories should be routinely examined during a behavioral evaluation to
      determine whether additional attempts at non-surgical weight loss are advisable.
      Future studies also are needed to explore the potential relationship between
      dieting history and postoperative outcome.

PMID- 16648598
TI  - Night eating syndrome and binge eating disorder among persons seeking bariatric
      surgery: prevalence and related features.
AB  - OBJECTIVE: To assess the prevalence of night eating syndrome (NES) and binge
      eating disorder (BED) and their related behavioral and psychological correlates
      in persons who sought bariatric surgery. RESEARCH METHODS AND PROCEDURES: A
      consecutive series of 215 persons with extreme obesity (82% women, 70% European
      American) completed the Weight and Lifestyle Inventory and a semistructured
      interview as part of a pre-surgery behavioral/psychological assessment. Diagnoses
      for NES and BED were based on graded diagnostic criteria. RESULTS: Percentages of
      participants who met diagnostic criteria for NES by interview were 1.9% for the
      strictest definition and 8.9% across all definitions of NES. After interview,
      full DSM-TR criteria for BED were met by 4.2%; an additional 1.4% reported binge
      eating at least once per week. Self-reported prevalence of NES and BED were
      higher. Those with NES or BED had significantly more symptoms of depression and a
      greater history of psychological complications than the remaining sample.
      DISCUSSION: The prevalence rates of NES and BED among this population of
      bariatric surgery candidates were lower than expected based on previous reports.
      Findings and hypotheses regarding lowered prevalence rates are discussed.

PMID- 16648599
TI  - Self-reported eating behaviors of extremely obese persons seeking bariatric
      surgery: a factor analytic approach.
AB  - OBJECTIVE: To summarize the self-reported eating behaviors of persons seeking
      bariatric surgery and to provide reliability data for a clinical instrument that
      assesses those eating behaviors. RESEARCH METHODS AND PROCEDURES: Adults (552)
      with extreme obesity (mean +/- standard deviation BMI = 52.4 +/- 10.1 kg/m(2))
      completed the Weight and Lifestyle Inventory (WALI) before undergoing bariatric
      surgery. The WALI is a self-report instrument that includes 24 items that assess
      the eating behaviors to which respondents attribute their excess weight. These
      items were entered into a principal components analysis with promax rotation.
      Relationships of factor scores to demographic and psychosocial variables were
      examined. Test-retest reliability data were obtained from a smaller sample (n =
      58) of less obese participants (BMI = 34.4 +/- 4.0 kg/m(2)) who completed the
      WALI twice within 2 weeks, before beginning a non-surgical weight loss program.
      RESULTS: The principal components analysis yielded five factors with acceptable
      internal consistency and test-retest reliability. These included: eating in
      response to negative affect, eating in response to positive affect and social
      cues, general overeating and impaired appetite regulation, overeating at early
      meals, and snacking. Each factor was related to symptoms of binge eating
      disorder, and every factor except the second one was associated with depressive
      symptoms. Factor scores were unrelated or weakly associated with demographic
      characteristics. DISCUSSION: The eating behaviors of persons seeking bariatric
      surgery can be assessed reliably and parsimoniously with the WALI. The predictive
      utility of the factors obtained in this study remains to be examined.

PMID- 16648600
TI  - Comparison of psychosocial status in treatment-seeking women with class III vs.
      class I-II obesity.
AB  - OBJECTIVE: This study compared the psychosocial status and weight loss
      expectations of women with extreme (class III) obesity who sought bariatric
      surgery with those of women with class I-II obesity who enrolled in a research
      study on behavioral weight control. RESEARCH METHODS AND PROCEDURES: Before
      treatment, all participants completed the Beck Depression Inventory-II and the
      Weight and Lifestyle Inventory. This latter questionnaire assesses several
      domains including symptoms of depression and low self-esteem, history of
      psychiatric complications, current stressors, and weight loss expectations.
      RESULTS: Women with class III obesity, as compared with class I-II, reported
      significantly more symptoms of depression. Fully 25% of women in the former group
      appeared to have a significant mood disorder that would benefit from treatment.
      As compared with women with class I-II obesity, significantly more women with
      class III obesity also reported a history of psychiatric complications, which
      included physical and sexual abuse and greater stress related to their physical
      health and financial/legal matters. Both groups of women had unrealistic weight
      loss expectations. Those who sought surgery expected to lose 47.6 +/- 9.3% of
      initial weight, compared with 24.8 +/- 8.7% for those who enrolled in behavioral
      weight control. DISCUSSION: These findings suggest that women with extreme
      obesity who seek bariatric surgery should be screened for psychosocial
      complications. Those determined to have significant psychiatric distress should
      be referred for behavioral or pharmacological treatment to alleviate their
      suffering. Long-term studies are needed to provide definitive guidance concerning
      the relationship between preoperative psychopathology and the outcome of
      bariatric surgery.

PMID- 16648601
TI  - Weight and Lifestyle Inventory (WALI).

PMID- 16648602
TI  - Child feeding practices and the etiology of obesity.

PMID- 16648603
TI  - Neurobiology of exercise.
AB  - Voluntary physical activity and exercise training can favorably influence brain
      plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective
      processes. At least some of the processes are mediated by neurotrophic factors.
      Motor skill training and regular exercise enhance executive functions of
      cognition and some types of learning, including motor learning in the spinal
      cord. These adaptations in the central nervous system have implications for the
      prevention and treatment of obesity, cancer, depression, the decline in cognition
      associated with aging, and neurological disorders such as Parkinson's disease,
      Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic
      voluntary physical activity also attenuates neural responses to stress in brain
      circuits responsible for regulating peripheral sympathetic activity, suggesting
      constraint on sympathetic responses to stress that could plausibly contribute to
      reductions in clinical disorders such as hypertension, heart failure, oxidative
      stress, and suppression of immunity. Mechanisms explaining these adaptations are
      not as yet known, but metabolic and neurochemical pathways among skeletal muscle,
      the spinal cord, and the brain offer plausible, testable mechanisms that might
      help explain effects of physical activity and exercise on the central nervous
      system.

PMID- 16648604
TI  - Intramyocellular lipid content in human skeletal muscle.
AB  - Fat can be stored not only in adipose tissue but also in other tissues such as
      skeletal muscle. Fat droplets accumulated in skeletal muscle [intramyocellular
      lipids (IMCLs)] can be quantified by different methods, all with advantages and
      drawbacks. Here, we briefly review IMCL quantification methods that use biopsy
      specimens (biochemical quantification, electron microscopy, and histochemistry)
      and non-invasive alternatives (magnetic resonance spectroscopy, magnetic
      resonance imaging, and computed tomography). Regarding the physiological role, it
      has been suggested that IMCL serves as an intracellular source of energy during
      exercise. Indeed, IMCL content decreases during prolonged submaximal exercise,
      and analogously to glycogen, IMCL content is increased in the trained state. In
      addition, IMCL content is highest in oxidative, type 1 muscle fibers. Together,
      this, indeed, suggests that the IMCL content is increased in the trained state to
      optimally match fat oxidative capacity and that it serves as readily available
      fuel. However, elevation of plasma fatty acid levels or dietary fat content also
      increases IMCL content, suggesting that skeletal muscle also stores fat simply if
      the availability of fatty acids is high. Under these conditions, the uptake into
      skeletal muscle may have negative consequences on insulin sensitivity. Besides
      the evaluation of the various methods to quantify IMCLs, this perspective
      describes IMCLs as valuable energy stores during prolonged exercise, which,
      however, in the absence of regular physical activity and with overconsumption of
      fat, can have detrimental effects on muscular insulin sensitivity.

PMID- 16648605
TI  - Left ventricular mass and +276 G/G single nucleotide polymorphism of the
      adiponectin gene in uncomplicated obesity.
AB  - The single nucleotide polymorphism at position 276 in the adiponectin gene
      (APM1/ACDC +276 G>T) and left ventricular mass (LVM) have been associated with
      increased cardiovascular risk. We sought to evaluate whether +276 G>T variants in
      the adiponectin gene are correlated with LVM in uncomplicated obese subjects.
      APM1/ACDC +276 G>T single nucleotide polymorphism, echocardiographic indexed LVM
      (LVM/body surface area and LVM/height(2.7)), insulin sensitivity by euglycemic
      clamp, and plasma adiponectin levels were analyzed in 62 obese subjects without
      complications (51 women and 11 men; mean age, 34.2 +/- 10.2 years; BMI, 38.6 +/-
      9.1 kg/m2). Forty lean subjects formed the control group for LVM evaluation. We
      found 23 (37%) uncomplicated obese subjects with the APM1/ACDC +276 G/G genotype,
      25 (40%) with the G/T genotype, and 14 (23%) with the T/T genotype. G/G
      uncomplicated obese subjects showed significant higher LVM/body surface area and
      LVM/height(2.7) (within the normal range in the majority of them) than
      uncomplicated obese subjects carrying the G/T and T/T genotypes (p < 0.01 and p <
      0.05, respectively). This study showed that LVM is significantly higher in
      uncomplicated obese subjects carrying the G/G genotype at position 276 of the
      human adiponectin gene.

PMID- 16648606
TI  - Prevalence of obese patients in a primary care setting.
AB  - OBJECTIVE: Previous research has addressed the relationship between BMI and
      chronic disease in primary care; however, little has been done with regard to the
      association between obesity and depression in primary care. The purpose of this
      paper is to assess the relationship between obesity and chronic conditions
      including depression. RESEARCH METHODS AND PROCEDURES: Data from primary care
      patients seen at a university-based family medicine clinic in the southeastern
      United States were extracted for the time between January 1, 1999 and January 1,
      2002. Data extracted included most recent height and weight, age, ethnicity,
      pregnancy status, number of office visits, blood pressure, cholesterol,
      hemoglobin A1C, current diagnoses, and medications. RESULTS: A total of 8197
      patients were included in the analysis. Sixty-nine percent of patients seen in a
      3-year period were either overweight or obese. Comparing blood pressure,
      cholesterol, diagnoses, and medications between BMI groups found differences in
      virtually all categories. Diagnoses of high cholesterol, hypertension, diabetes,
      and depression significantly increased for obese patients. DISCUSSION: Obese
      patients are over-represented in primary care, and this over-representation of
      obesity correlates with several diagnoses, including depression. Depression is a
      chronic disease that may interfere with health-related behaviors and must be
      addressed within the health care system.

PMID- 16648607
TI  - High prevalence of the metabolic syndrome in Iranian adolescents.
AB  - OBJECTIVE: No evidence exists regarding the prevalence of the metabolic syndrome
      in adolescents in Middle Eastern countries. We aimed to evaluate the prevalence
      of the metabolic syndrome in a representative sample of Iranian adolescents.
      RESEARCH METHODS AND PROCEDURES: Anthropometry, biochemical measurements, and
      blood pressure were assessed in a population-based cross-sectional study of 3036
      Iranian adolescents (1413 boys and 1623 girls) 10 to 19 years of age. Metabolic
      syndrome was defined according to modified Adult Treatment Panel III definition.
      Overweight (> or = 95th percentile) and at risk for overweight (> or = 85th to <
      95th percentile) was defined based on the standardized percentile curves of BMI
      suggested for Iranian adolescents. RESULTS: The prevalence of the metabolic
      syndrome was 10.1% (95% confidence interval: 9.0 to 11.1) among Iranian
      adolescents (boys: 10.3%, 8.6 to 11.8; girls: 9.9%, 8.4 to 11.3). Overall, low
      serum high-density lipoprotein-cholesterol and high serum triglycerides were the
      most common components of the metabolic syndrome (42.8% and 37.5%, respectively).
      Overweight subjects had the highest proportion of metabolic syndrome compared
      with those at risk for overweight and those with normal weight (boys: 41.1% vs.
      11.4% and 3.0%, respectively, p < 0.01; girls: 43% vs. 15.2% and 5.0%,
      respectively, p < 0.01). DISCUSSION: This study provides evidence showing a high
      prevalence of the metabolic syndrome in Iranian adolescents, particularly among
      overweight adolescents.

PMID- 16648608
TI  - Effect of gastric bypass on spontaneous growth hormone and ghrelin release
      profiles.
AB  - OBJECTIVE: The purpose of this study was to analyze growth hormone (GH)
      concentrations in obese women before and after Roux-en-Y gastric bypass (RYGBP)
      and how resulting changes in weight, fat mass, ghrelin levels, and insulin
      sensitivity affect GH secretion. RESEARCH METHODS AND PROCEDURES: Blood was
      sampled at 20-minute intervals for 24 hours in 10 non-diabetic premenopausal
      severely obese women before and 6 months after RYGBP. GH concentrations were
      measured in all samples, and serum ghrelin was collected at five time-points.
      RESULTS: After a 27% BMI drop (55.9 +/- 6.2 to 40.7 +/- 5.8 kg/m2), blunted GH
      profiles underwent partial recovery. Basal, postprandial, and mean ghrelin
      concentrations were not changed. A negative correlation was found between mean GH
      levels and insulin and homeostasis model assessment (p < 0.01). BMI accounted for
      54% of GH variation. DISCUSSION: Partial recovery of GH secretion after RYGBP
      induced weight loss suggests that a blunted secretion is not a causal factor of
      obesity but a consequence of the obese state and does not seem to be ghrelin
      level dependent.

PMID- 16648609
TI  - Molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes.
AB  - OBJECTIVE: Determine the biochemical pathways involved in induction of apoptosis
      by ajoene, an organosulfur compound from garlic. RESEARCH METHODS AND PROCEDURES:
      Mature 3T3-L1 adipocytes were incubated with ajoene at concentrations up to 200
      microM. Viability and apoptosis were quantified using an MTS-based cell viability
      assay and an enzyme-linked immunosorbent assay for single-stranded DNA (ssDNA),
      respectively. Intracellular reactive oxygen species (ROS) production was measured
      based on production of the fluorescent dye, dichlorofluorescein. Activation of
      the mitogen-activated protein kinases extracellular signal-regulating kinase 1/2
      (ERK) and c-Jun-N-terminal kinase (JNK) was shown by Western blot. Western blot
      was also used to show activation of caspase-3, translocation of apoptosis
      inducing factor (AIF) from mitochondria to nucleus, and cleavage of 116-kDa
      poly(ADP-ribose) polymerase (PARP)-1. RESULTS: Ajoene induced apoptosis of 3T3-L1
      adipocytes in a dose- and time-dependent manner. Ajoene treatment resulted in
      activation of JNK and ERK, translocation of AIF from mitochondria to nucleus, and
      cleavage of 116-kDa PARP-1 in a caspase-independent manner. Ajoene treatment also
      induced an increase in intracellular ROS level. Furthermore, the antioxidant N
      acetyl-L-cysteine effectively blocked ajoene-mediated ROS generation, activation
      of JNK and ERK, translocation of AIF, and degradation of PARP-1. DISCUSSION:
      These results indicate that ajoene-induced apoptosis in 3T3-L1 adipocytes is
      initiated by the generation of hydrogen peroxide, which leads to activation of
      mitogen-activated protein kinases, degradation of PARP-1, translocation of AIF,
      and fragmentation of DNA. Ajoene can, thus, influence the regulation of fat cell
      number through the induction of apoptosis and may be a new therapeutic agent for
      the treatment of obesity.

PMID- 16648610
TI  - Effect of endothelin-1 on lipolysis in rat adipocytes.
AB  - OBJECTIVE: To explore the role of endothelin-1 (ET-1) on lipid metabolism, we
      examined the effect of ET-1 on lipolysis in rat adipocytes. RESEARCH METHODS AND
      PROCEDURE: Adipocytes isolated from male Sprague-Dawley rats, weighing 400 to 450
      grams, were incubated in Krebs-Ringer buffer with or without 10(-7) M ET-1 for
      various times or with various concentrations of ET-1 for 4 hours; then glycerol
      release into the incubation medium was measured. In addition, selective ET(A)R
      and ET(B)R blockers were used to identify the ET receptor subtype involved. We
      also explored the involvement of cyclic adenosine monophosphate (cAMP) in ET-1
      stimulated lipolysis using an adenylyl cyclase inhibitor and by measuring changes
      in intracellular cAMP levels in response to ET-1 treatment. To further explore
      the underlying mechanism of ET-1 action, we examined the involvement of the
      extracellular signal-regulated kinase (ERK)-mediated pathways. RESULTS: Our
      results showed that ET-1 caused lipolysis in rat adipocytes in a time- and dose
      dependent manner. BQ610, a selective ET(A)R blocker, blocked this effect. The
      adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine, had no effect on ET-1
      stimulated lipolysis. ET-1 did not induce an increase in intracellular cAMP
      levels. In addition, ET-1-induced lipolysis was blocked by inhibition of ERK
      activation using PD98059. Coincubation of cells with ET-1 and insulin suppressed
      ET-1-stimulated lipolysis. DISCUSSION: These findings show that ET-1 stimulates
      lipolysis in rat adipocytes through the ET(A)R and activation of the ERK pathway.
      The underlying mechanism is cAMP-independent. However, this non-conventional
      lipolytic effect of ET-1 is inhibited by the anti-lipolytic effect of insulin.

PMID- 16648611
TI  - In vivo phenotyping of the ob/ob mouse by magnetic resonance imaging and 1H
      magnetic resonance spectroscopy.
AB  - OBJECTIVE: We studied ob/ob and wild-type (WT) mice to characterize the adipose
      tissues depots and other visceral organs and to establish an experimental
      paradigm for in vivo phenotyping. RESEARCH METHODS AND PROCEDURES: An in vivo
      evaluation was conducted using magnetic resonance imaging and 1H-magnetic
      resonance spectroscopy (1H-MRS). We used T1-weighted images and three-dimensional
      spin echo T1-weighted images for the morphological analysis and 1H-MRS spectra on
      all body mass, as well as 1H-MRS spectra focalized on specific lipid depots
      [triglyceride (TG) depots] for a molecular analysis. RESULTS: In ob/ob mice,
      three-dimensional evaluation of the trunk revealed that approximately 64% of the
      volume consists of white adipose tissue, which is 72% subcutaneous and 28%
      visceral. In vivo 1H-MRS showed that 20.00 +/- 6.92% in the WT group and 58.67 +/
      6.65% in the ob/ob group of the total proton content is composed of TG protons.
      In in vivo-localized spectra of ob/ob mice, we found a polyunsaturation degree of
      0.5247 in subcutaneous depots. In the liver, we observed that 48.7% of the proton
      signal is due to water, whereas in the WT group, the water signal amounted to
      82.8% of the total proton signal. With the sequences used, the TG amount was not
      detectable in the brain or kidneys. DISCUSSION: The present study shows that
      several parameters can be obtained by in vivo examination of ob/ob mice by
      magnetic resonance imaging and 1H-MRS and that the accumulated white adipose
      tissue displays low polyunsaturation degree and low hydrolipidic ratio. Relevant
      anatomical alterations observed in urinary and digestive apparatuses should be
      considered when ob/ob mice are used in experimental paradigms.

PMID- 16648612
TI  - Comparison of body composition methods in obese African-American women.
AB  - OBJECTIVE: To compare the accuracy of percentage body fat (%BF) estimates between
      bioelectrical impedance analysis (BIA) and DXA in obese African-American women.
      RESEARCH METHODS AND PROCEDURES: Fifty-five obese African-American women (mean
      age, 45 years; mean BMI, 38; mean %BF, 48%) were studied. BF was assessed by both
      BIA (RJL Systems BIA 101Q; RJL Systems, Clinton Township, MI) and DXA (Hologic
      QDR-2000 Bone Densitometer; Hologic Inc., Bedford, MA). Generalized and ethnicity
      and obese-specific equations were used to calculate %BF from the BIA. Bland
      Altman analyses were used to compare the agreement between the BIA and the DXA,
      with the DXA serving as the criterion measure. RESULTS: Two of the generalized
      equations provided consistent estimates across the weight range in comparison
      with the DXA estimates, whereas most of the other equations increasingly
      underestimated %BF as BF increased. One of the generalized and one of the
      ethnicity-specific equations had mean differences that were not significantly
      different from the DXA value. DISCUSSION: The findings show that the Lukaski
      equation provided the most precise and accurate estimates of %BF in comparison
      with the QDR 2000 and provide preliminary support for the use of this equation
      for obese African-American women.

PMID- 16648613
TI  - The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and
      lipid metabolism.
AB  - OBJECTIVE: Increased intake of dietary fiber reduces the risk of obesity and type
      2 diabetes. We assessed the effects of a fiber-rich diet on body weight,
      adipokine concentrations, and the metabolism of glucose and lipids in non-obese
      and obese subjects in Korea, where rice is the main source of dietary
      carbohydrates. RESEARCH METHODS AND PROCEDURES: Eleven healthy, non-obese and 10
      obese subjects completed two 4-week phases of individual isoenergetic food
      intake. During the control diet phase, subjects consumed standard rice; during
      the modified diet phase, subjects consumed equal proportions of fiber-rich Goami
      No. 2 rice and standard rice. We used a randomized, controlled, crossover study
      design with a washout period of 6 weeks between the two phases. RESULTS: After
      the modified diet phase, body weight was significantly lower in both the non
      obese and obese subjects (non-obese, 57.0 +/- 2.9 vs. 56.1 +/- 2.8 kg, p = 0.001;
      obese, 67.7 +/- 2.1 vs. 65.7 +/- 2.0 kg, p < 0.001 for before vs. after). The BMI
      was significantly lower in obese subjects (26.9 +/- 0.5 vs. 26.0 +/- 0.6 kg/m2, p
      < 0.001). The modified diet was associated with lower serum triacylglycerol (p <
      0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p <
      0.05), and C-peptide (p < 0.05) concentrations in the obese subjects. DISCUSSION:
      These results indicate that fiber-rich Goami No. 2 rice has beneficial effects
      and may be therapeutically useful for obese subjects.

PMID- 16648614
TI  - Influence of parents' eating behaviors and child feeding practices on children's
      weight status.
AB  - OBJECTIVE: To investigate the effects of mothers' and fathers' eating behaviors,
      child feeding practices, and BMI on percentage body fat and BMI in their
      children. RESEARCH METHODS AND PROCEDURES: Four hundred fifty-eight parents (239
      mothers, 219 fathers) were asked to complete two questionnaires: the Three-Factor
      Eating Questionnaire and the Child Feeding Questionnaire, which measure
      dimensions of parent eating behavior and child feeding practices, respectively.
      Parent BMI was calculated from self-reported height and weight; children's
      measures included BMI and percentage fat assessed by DXA. Regression analyses
      were used to analyze relationships between parents' BMI and questionnaire scores
      and children's weight status. RESULTS: One hundred forty-three mothers and 68
      fathers returned questionnaires, representing parents of 148 children 3 to 5
      years old (78 boys). Children's weight was related to mothers' BMI, but not
      fathers'. Girls had a greater BMI if either parent reported being overweight as a
      child, and both girls and boys were likely to be overweight if their mothers
      believed they had risky eating habits (fussiness, eating too much, etc.). Girls
      with fathers who were more controlling had a higher percentage fat; these fathers
      were also more concerned about their daughters' future health. DISCUSSION:
      Mothers exert a strong influence over their children's weight and seem to be more
      concerned about their children's eating behaviors; however, fathers play a role
      in imposing child feeding practices. Gender bias may be present in child feeding,
      as suggested by dissimilar effects of parent practices on the weight status of
      girls vs. boys. Fathers should be included in future studies analyzing parent
      feeding practices and children's weight outcome.

PMID- 16648615
TI  - The influence of one's own body weight on implicit and explicit anti-fat bias.
AB  - OBJECTIVE: This study examined the influence of one's own body weight on the
      strength of implicit and explicit anti-fat bias. RESEARCH METHODS AND PROCEDURE:
      Implicit and explicit anti-fat attitudes and obesity stereotypes were assessed
      among a large online sample (N = 4283) that included representation from across
      the weight spectrum (from underweight to extremely obese). Respondents also
      indicated their willingness to make a range of personal sacrifices in exchange
      for not being obese. RESULTS: All weight groups exhibited significant anti-fat
      bias, but there was an inverse relation between one's own weight and the level of
      observed bias. Thinner people were more likely to automatically associate
      negative attributes (bad, lazy) with fat people, to prefer thin people to fat
      people, and to explicitly rate fat people as lazier and less motivated than thin
      people. However, when the lazy stereotype was contrasted with another negative
      attribute (anxious), obese and non-obese people exhibited equally strong implicit
      stereotyping. Finally, a substantial proportion of respondents indicated a
      willingness to endure aversive life events to avoid being obese. For example, 46%
      of the total sample indicated that they would rather give up 1 year of life than
      be obese, and 30% reported that they would rather be divorced than be obese. In
      each case, thinner people were more willing to sacrifice aspects of their health
      or life circumstances than were heavier people. DISCUSSION: Although the strength
      of weight bias decreased as respondents' body weight increased, a significant
      degree of anti-fat bias was still evident among even the most obese group of
      respondents, highlighting the pervasiveness of this bias.

PMID- 16648616
TI  - Assessing weight-related quality of life in adolescents.
AB  - OBJECTIVE: The development of a new weight-related measure to assess quality of
      life in adolescents [Impact of Weight on Quality of Life (IWQOL)-Kids] is
      described. RESEARCH METHODS AND PROCEDURES: Using a literature search, clinical
      experience, and consultation with pediatric clinicians, 73 items were developed,
      pilot tested, and administered to 642 participants, 11 to 19 years old, recruited
      from weight loss programs/studies and community samples (mean z-BMI, 1.5; range, 
      1.2 to 3.4; mean age, 14.0; 60% female; 56% white). Participants completed the 73
      items and the Pediatric Quality of Life Inventory and were weighed and measured.
      RESULTS: Four factors (27 items) were identified (physical comfort, body esteem,
      social life, and family relations), accounting for 71% of the variance. The IWQOL
      Kids demonstrated excellent psychometric properties. Internal consistency
      coefficients ranged from 0.88 to 0.95 for scales and equaled 0.96 for total
      score. Convergent validity was demonstrated with strong correlations between
      IWQOL-Kids total score and the Pediatric Quality of Life Inventory (r = 0.76, p <
      0.0001). Significant differences were found across BMI groups and between
      clinical and community samples, supporting the sensitivity of this measure.
      Participants in a weight loss camp demonstrated improved IWQOL-Kids scores,
      suggesting responsiveness of the IWQOL-Kids to weight loss/social support
      intervention. DISCUSSION: The present study provides preliminary evidence
      regarding the psychometric properties of the IWQOL-Kids, a weight-related quality
      of life measure for adolescents. Given the rise of obesity in youth, the
      development of a reliable and valid weight-related measure of quality of life is
      timely.

PMID- 16648617
TI  - Psychological workload and weight gain among women with and without familial
      obesity.
AB  - OBJECTIVE: High job demands and low job influence may be associated with
      subsequent weight gain. Predisposition to obesity may further modify such
      associations. The purpose of the study was to determine whether familial
      predisposition to obesity modified associations between psychological workload
      and 6-year weight changes among nurses. RESEARCH METHODS AND PROCEDURES: A total
      of 6404 Danish nurses 45 to 65 years old, who belonged to the workforce in both
      1993 and 1999, answered a questionnaire on psychological workload, body weight,
      and familial obesity. Women were considered to be predisposed to obesity if they
      were overweight and had at least one obese parent. Parents' body shape was
      reported using pictograms. RESULTS: An increased psychological workload,
      reflected by high job demands and low influence in job, was associated with an
      increased body weight. This was particularly the case for nurses being
      predisposed to obesity, suggesting a synergy between familial obesity
      predisposition and the psychological workload environment. An interaction test
      among job demands, familial predisposition to obesity, and weight gain on
      adjusted data was made. The test showed p = 0.05. The adjusted interaction test
      among influence in job, familial predisposition to obesity, and weight gain
      showed p = 0.02. Predisposed nurses who were busy in their job gained 4.4 kg,
      whereas other nurses gained only 3.2 kg during the 6 years. Similarly, nurses
      predisposed to obesity with low influence in job had a higher body weight gain
      (5.4 vs. 3.2 kg) compared with other nurses. DISCUSSION: High psychological
      workload due to high job demands and low influence in job seems to predict weight
      gain in general and, in particular, among those nurses with a familial
      predisposition to obesity.

PMID- 16648618
TI  - The perceived effectiveness of continuing care and group support in the long-term
      self-help treatment of obesity.
AB  - OBJECTIVE: Obesity is increasingly considered a chronic disease requiring
      continuing care, but professional long-term treatment for most patients is not
      available. This study examined treatment recipients' perception of the
      effectiveness of different components of a group self-help, continuing-care
      treatment program for obesity. RESEARCH METHODS AND PROCEDURES: Members (n = 120)
      and volunteer leaders (n = 66) of a self-help, continuing-care treatment program
      of previously demonstrated effectiveness (mean treatment duration, 40.6 months;
      mean weight lost, 14.1 kg) rated how helpful and effective they found the various
      therapeutic strategies used by this program. The strategies examined were
      continuing care, group support, behavior therapy, motivational enhancement
      strategies involving positive reinforcement, and motivational enhancement
      strategies involving punishment. RESULTS: The single most highly valued aspect of
      treatment was the provision of continuing care, followed by group support.
      Greater success at achieving one's goal weight was associated with perceptions of
      greater effectiveness of the program's strategies overall (r = 0.219, p < 0.005),
      of continuing care (r = 0.225, p < 0.005), and of positive reinforcement
      strategies (r = 0.223, p < 0.01). Participants who had successfully attained
      their goal weight perceived behavior therapy strategies as more effective than
      did participants who had not reached their goal weight [t(170) = 2.93, p <
      0.005]. DISCUSSION: The high ratings given to continuing care and group support
      strategies indicate the acceptability of supportive self-help treatment for
      obesity administered over the long term. The findings suggest that continuing
      care and group support should be made available to participants in the self-help
      treatment of obesity.

PMID- 16648619
TI  - Obesity and sexual quality of life.
AB  - OBJECTIVES: Reduced sexual quality of life is a frequently reported yet rarely
      studied consequence of obesity. The objectives of this study were to 1) examine
      the prevalence of sexual quality-of-life difficulties in obese individuals and 2)
      investigate the association between sexual quality of life and BMI class, sex,
      and obesity treatment-seeking status. RESEARCH METHODS AND PROCEDURES: Subjects
      consisted of 1) 500 participants in an intensive residential program for weight
      loss and lifestyle modification (BMI = 41.3 kg/m2), 2) 372 patients evaluated for
      gastric bypass surgery (BMI = 47.1 kg/m2), and 3) 286 obese control subjects not
      seeking weight loss treatment (BMI = 43.6 kg/m2). Participants completed the
      Impact of Weight on Quality of Life-Lite, a measure of weight-related quality of
      life. Responses to the four Sexual Life items (assessing enjoyment, desire,
      performance, and avoidance) were analyzed by BMI, sex, and group. RESULTS: Higher
      BMI was associated with greater impairments in sexual quality of life. Obese
      women reported more impairment in sexual quality of life than obese men for three
      of four items. Gastric bypass surgery candidates reported more impairment in
      sexual quality of life than residential patients and controls for most items. In
      general, residential patients reported levels of impairment greater than or equal
      to controls. DISCUSSION: Obesity is associated with lack of enjoyment of sexual
      activity, lack of sexual desire, difficulties with sexual performance, and
      avoidance of sexual encounters. Sexual quality of life is most impaired for
      women, individuals with Class III obesity, and patients seeking gastric bypass
      surgery.

PMID- 16648620
TI  - Comparison of bioelectrical impedance and BMI in predicting obesity-related
      medical conditions.
AB  - OBJECTIVE: To determine the relative validity of specific bioelectrical impedance
      analysis (BIA) prediction equations and BMI as predictors of physiologically
      relevant general adiposity. RESEARCH METHODS AND PROCEDURES: Subjects were
      >12,000 men and women from the Third National Health and Nutrition Examination
      Survey population. We examined the correlations between BMI and percentage body
      fat based on 51 different predictive equations, blood pressure, and blood levels
      of glucose, high-density lipoprotein cholesterol, and triglycerides, which are
      known to reflect adiposity, while controlling for other determinants of these
      physiological measures. RESULTS: BMI consistently had one of the highest
      correlations across biological markers, and no BIA-based measure was superior.
      Percent body fat estimated from BIA was minimally predictive of the physiological
      markers independent of BMI. DISCUSSION: These results suggest that BIA is not
      superior to BMI as a predictor of overall adiposity in a general population.

PMID- 16648621
TI  - Rapid infant weight gain predicts childhood overweight.
AB  - OBJECTIVE: To determine among a contemporary cohort whether rapid weight gain
      between birth and 6 months is associated with risk of childhood overweight and if
      this risk differs by ethnicity and/or breast-feeding history. RESEARCH METHODS
      AND PROCEDURES: This was a cross-sectional survey in 1999 to 2000 of
      parents/guardians of children participating in the Special Supplemental Nutrition
      Program for Women, Infants, and Children in New York State. Measurements were
      abstracted by chart review, including weight at birth and 6 months, and height
      and weight at time of survey and every 6 months subsequently. Overweight at 4
      years of age was defined as a BMI > or = 95th age- and sex-specific percentiles.
      RESULTS: The study sample was 32% Hispanic, 19% black, and 49% white; 17% of
      children were overweight. Rate of infant weight gain (expressed in terms of 100
      g/mo) was significantly associated with being overweight at 4 years (odds ratio,
      1.4; 95% confidence interval, 1.3 to 1.6 after adjusting for history of breast
      feeding, birth weight, and ethnicity). The odds of being overweight at 4 years of
      age for Hispanic children were twice those of non-Hispanic children (odds ratio,
      2.2; 95% confidence interval, 1.5 to 3.3). The population-attributable risk of
      overweight at 4 years of age was 19% for children in the highest quintile of
      infant weight gain. DISCUSSION: Among this contemporary, multi-ethnic cohort,
      rapid infant weight gain was associated with increased risk of being overweight
      at 4 years of age, independently of potential confounders. Identification of the
      risk factors contributing to rapid weight gain during infancy might improve early
      recognition and guide strategies for optimal nutrition to prevent the development
      of childhood overweight.

PMID- 16648622
TI  - Lifestyle variables, non-traditional cardiovascular risk factors, and the
      metabolic syndrome in an Aboriginal Canadian population.
AB  - OBJECTIVE: To examine lifestyle factors associated with metabolic syndrome (MetS)
      and to explore the relationships between MetS and non-traditional cardiovascular
      disease risk factors [adiponectin, leptin, C-reactive protein (CRP), interleukin
      6 (IL-6), and serum amyloid A (SAA)] in an isolated Aboriginal Canadian
      community. RESEARCH METHODS AND PROCEDURES: Data were obtained from 360 non
      diabetic adults participating in a population-based study of Aboriginal
      Canadians. Fasting samples were drawn for glucose, insulin, lipids, adiponectin,
      leptin, CRP, IL-6, and SAA. Percentage body fat was measured using bioelectrical
      impedance analysis. Past year physical activity and fitness level were assessed.
      MetS was diagnosed according to the criteria of the National Cholesterol
      Education Program, the World Health Organization, and the International Diabetes
      Federation. RESULTS: The results showed that older age, higher percentage body
      fat, and lower fitness levels were associated with increased odds of MetS
      regardless of MetS definition and subject gender. Past year physical activity was
      independently related with the World Health Organization-MetS in male subjects.
      Subjects with MetS had significantly higher leptin, CRP, IL-6, and SAA levels and
      lower adiponectin levels; however, only adiponectin remained significantly low
      after adjustment for age and percentage body fat. DISCUSSION: The study showed
      that higher percentage body fat and lower physical activity and fitness were
      associated with a higher prevalence of MetS in this Aboriginal community and that
      hypoadiponectinemia was independently associated with MetS.

PMID- 16648623
TI  - Obesity is a risk factor for reporting homebound status among community-dwelling
      older persons.
AB  - OBJECTIVE: To test the a priori hypothesis that obesity is a predictor of risk
      for reporting homebound status. RESEARCH METHODS AND PROCEDURES: A longitudinal
      cohort study was conducted with 21,645 community-dwelling men and women 65 to 97
      years old. A nutrition risk screen was administered baseline between 1994 and
      1999 and again 3 to 4 years later. Univariate analyses identified baseline
      variables associated with subsequent reporting of homebound status. Multivariable
      logistic regression models were created to identify baseline variables that were
      significant independent predictors of reporting homebound status. RESULTS: At
      baseline, 24% of the cohort had BMI > or = 30. There were 12,834 (45% men)
      respondents at follow-up (68% response). Non-responders at follow-up differed
      little from responders except for greater baseline age (72.2 +/- 6.2 vs. 71.4 +/-
      5.6 years, p < 0.001) and reporting of any functional limitations (9.2% vs. 4.9%,
      p < 0.001). At follow-up, those who reported homebound status (n = 169) were
      significantly (p < 0.001) older (80.3 +/- 7.3 vs. 75.1 +/- 5.5 years) and more
      likely to report functional limitations (83.4% vs. 10.8%). Univariate analyses
      identified 16 baseline variables that were eliminated stepwise until five
      significant independent predictors remained: age > or = 75 years (2.21, 1.55 to
      3.15/odds ratio, 95% confidence interval), BMI > or = 35 (1.75, 1.04 to 2.96),
      poor appetite (2.50, 1.29 to 4.86), low income (1.59, 1.00 to 2.56), and any
      functional limitation (10.67, 7.36 to 15.46). DISCUSSION: Obesity remained a
      significant independent predictor for reporting homebound status and should be
      considered in screening of older populations and in the planning, implementation,
      and evaluation of services for homebound older persons.

PMID- 16648624
TI  - Neighborhood safety, collective efficacy, and obesity in women with young
      children.
AB  - OBJECTIVE: To test the hypothesis that mothers of young children would have a
      higher prevalence of obesity if they lived in neighborhoods that they perceived
      as unsafe or as having a low level of collective efficacy. RESEARCH METHODS AND
      PROCEDURES: Using data from the Fragile Families and Child Wellbeing Study, a
      cross-sectional analysis was conducted of 2445 women living in 20 large
      (population > or = 200,000) U.S. cities. BMI was measured on 72% and self
      reported on 28%. Perception of neighborhood safety was assessed with the
      Neighborhood Environment for Children Rating Scales. The collective efficacy
      measure was adapted from the Project on Human Development in Chicago
      Neighborhoods. RESULTS: Thirty percent of the women were married, 38% lived below
      the U.S. poverty threshold, and 66% reported no education beyond high school.
      Approximately one-half of the women were non-Hispanic black, and one-fourth were
      Hispanic (any race). After adjustment for sociodemographic factors (household
      income, education, race/ethnicity, age, and marital status), smoking, depression,
      and television time, the prevalence of obesity (BMI > or = 30 kg/m2) increased
      across tertiles of neighborhood safety from safest to least safe (37% vs. 41% vs.
      46%, p = 0.004) but did not differ across tertiles of collective efficacy from
      highest to lowest (41% vs. 40% vs. 42%, p = 0.67). DISCUSSION: In a national
      sample of women with young children, obesity was more prevalent among those who
      perceived their neighborhoods to be unsafe.

PMID- 16648625
TI  - BMI and cervical cancer screening among white, African-American, and Hispanic
      women in the United States.

PMID- 16648627
TI  - Proteomics of plant detergent-resistant membranes.
AB  - A large body of evidence from the past decade supports the existence, in membrane
      from animal and yeast cells, of functional microdomains that play important roles
      in protein sorting, signal transduction, or infection by pathogens. Recent
      reports demonstrated the presence, in plants, of detergent-resistant fractions
      isolated from plasma membrane. Analysis of the lipidic composition of this
      fraction revealed its enrichment in sphingolipids and sterols and depletion in
      phospho- and glycerolipids as previously observed for animal microdomains. One
      dimensional gel electrophoresis experiments indicated that these detergent
      resistant fractions are able to recruit a specific set of plasma membrane
      proteins and exclude others. In the present study, we used mass spectrometry to
      give an extensive description of a tobacco plasma membrane fraction resistant to
      solubilization with Triton X-100. This led to the identification of 145 proteins
      whose functional and physicochemical characteristics were analyzed in silico.
      Parameters such as isoelectric point, molecular weight, number and length of
      transmembrane segments, or global hydrophobicity were analyzed and compared with
      the data available concerning plant plasma membrane proteins. Post-translational
      modifications, such as myristoylation, palmitoylation, or presence of a
      glycosylphosphatidylinositol anchor, were examined in relation to the presence of
      the corresponding proteins in these microdomains. From a functional point of
      view, this analysis indicated that if a primary function of the plasma membrane,
      such as transport, seems under-represented in the detergent-resistant fraction,
      others undergo a significant increase of their relative importance. Among these
      are signaling and response to biotic and abiotic stress, cellular trafficking,
      and cell wall metabolism. This suggests that these domains are likely to
      constitute, as in animal cells, signaling platforms involved in these
      physiological functions.

PMID- 16648628
TI  - Versican G3 domain regulates neurite growth and synaptic transmission of
      hippocampal neurons by activation of epidermal growth factor receptor.
AB  - Versican is one of the major extracellular matrix (ECM) proteins in the brain.
      ECM molecules and their cleavage products critically regulate the growth and
      arborization of neurites, hence adjusting the formation of neural networks.
      Recent findings have revealed that peptide fragments containing the versican C
      terminus (G3 domain) are present in human brain astrocytoma. The present study
      demonstrated that a versican G3 domain enhanced cell attachment, neurite growth,
      and glutamate receptor-mediated currents in cultured embryonic hippocampal
      neurons. In addition, the G3 domain intensified dendritic spines, increased the
      clustering of both synaptophysin and the glutamate receptor subunit GluR2, and
      augmented excitatory synaptic activity. In contrast, a mutated G3 domain lacking
      the epidermal growth factor (EGF)-like repeats (G3deltaEGF) had little effect on
      neurite growth and glutamatergic function. Treating the neurons with the G3
      conditioned medium rapidly increased the levels of phosphorylated EGF receptor
      (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK),
      indicating an activation of EGFR-mediated signaling pathways. Blockade of EGFR
      prevented the G3-induced ERK activation and suppressed the G3-provoked
      enhancement of neurite growth and glutamatergic function but failed to block the
      G3-mediated enhancement of cell attachment. These combined results indicate that
      the versican G3 domain regulates neuronal attachment, neurite outgrowth, and
      synaptic function of hippocampal neurons via EGFR-dependent and -independent
      signaling pathway(s). Our findings suggest a role for ECM proteolytic products in
      neural development and regeneration.

PMID- 16648629
TI  - A requirement for dimerization of HP1Hsalpha in suppression of breast cancer
      invasion.
AB  - The development and progression of cancer is controlled by gene expression, often
      regulated through chromatin packaging. Heterochromatin protein 1(Hsalpha)
      (HP1(Hsalpha)), one of three human HP1 family members, participates in
      heterochromatin formation and gene regulation. HP1(Hsalpha) possesses an amino
      terminal chromodomain, which binds methylated lysine 9 of histone H3 (meK9 H3),
      and a carboxyl-terminal chromoshadow domain (CSD) that is required for
      dimerization and interaction with partner proteins. HP1(Hsalpha) is down
      regulated in invasive metastatic breast cancer cells compared with poorly
      invasive nonmetastatic breast cancer cells. Expression of EGFP-HP1(Hsalpha) in
      highly invasive MDA-MB-231 cells causes a reduction in in vitro invasion, without
      affecting cell growth. Conversely, knock-down of HP1(Hsalpha) levels in the
      poorly invasive breast cancer cell line MCF-7 increased invasion, without
      affecting cell growth. To determine whether functions of the CSD were required
      for the regulation of invasion, mutant forms of HP1(Hsalpha) were expressed in
      MDA-MB-231 cells. A W174A mutation that disrupts interactions between
      HP1(Hsalpha) and PXVXL-containing partner proteins reduced invasion similar to
      that of the wild type protein. In contrast, an I165E mutation that disrupts
      dimerization of HP1(Hsalpha) did not decrease invasion. No gross changes in
      localization and abundance of HP1(Hsbeta), HP1(Hsgamma), and meK9 H3 were
      observed upon expression of wild type and mutant forms of HP1(Hsalpha) in MDA-MB
      231 cells. Taken together, these data demonstrate that modulation of HP1(Hsalpha)
      alters the invasive potential of breast cancer cells through mechanisms requiring
      HP1 dimerization, but not interactions with PXVXL-containing proteins.

PMID- 16648630
TI  - The microphthalmia-associated transcription factor requires SWI/SNF enzymes to
      activate melanocyte-specific genes.
AB  - The microphthalmia transcription factor (Mitf) activates melanocyte-specific gene
      expression, is critical for survival and proliferation of melanocytes during
      development, and has been described as an oncogene in malignant melanoma. SWI/SNF
      complexes are ATP-dependent chromatin-remodeling enzymes that play a role in many
      developmental processes. To determine the requirement for SWI/SNF enzymes in
      melanocyte differentiation, we introduced Mitf into fibroblasts that inducibly
      express dominant negative versions of the SWI/SNF ATPases, Brahma or Brahma
      related gene 1 (BRG1). These dominant negative SWI/SNF components have been shown
      to inhibit gene activation events that normally require SWI/SNF enzymes. We found
      that Mitf-mediated activation of a subset of endogenous melanocyte-specific genes
      required SWI/SNF enzymes but that cell-cycle regulation occurred independently of
      SWI/SNF function. Activation of tyrosinase-related protein 1, a melanocyte
      specific gene, correlated with SWI/SNF-dependent changes in chromatin
      accessibility at the endogenous locus. Both BRG1 and Mitf could be localized to
      the tyrosinase-related protein 1 and tyrosinase promoters by chromatin
      immunoprecipitation, whereas immunofluorescence and immunoprecipitation
      experiments indicate that Mitf and BRG1 co-localized in the nucleus and
      physically interacted. Together these results suggest that Mitf can recruit
      SWI/SNF enzymes to melanocyte-specific promoters for the activation of gene
      expression via induced changes in chromatin structure at endogenous loci.

PMID- 16648631
TI  - Identification and characterization of versican/PG-M aggregates in cartilage.
AB  - Versican/PG-M is a large chondroitin sulfate proteoglycan of the extracellular
      matrix with a common domain structure to aggrecan and is present in cartilage at
      low levels. Here, we characterized cartilage versican during development and
      growth. Immunostaining showed that versican was mainly localized in the
      interterritorial zone of the articular surface at 2 weeks in mice, whereas
      aggrecan was in the pericellular zone of prehypertrophic and hypertrophic cells
      of the growth plate. Although its transcription level rapidly diminished during
      growth, versican remained in the articular cartilage. Biochemical analysis of
      normal articular cartilage and aggrecan-null cartilage from cmd (cartilage matrix
      deficiency)/cmd mice revealed that versican was present as a proteoglycan
      aggregate with both link protein and hyaluronan. Chondroitin sulfate chains of
      versican digested with chondroitinase ABC contained 71% nonsulfated and 28% 4
      sulfated unsaturated disaccharides, whereas those of aggrecan contained 25%
      nonsulfated and 70% 4-sulfated. Link protein overexpression in chondrocytic N1511
      cells at the early stage of differentiation, in which versican is expressed,
      enhanced versican deposition in the matrix and prevented subsequent aggrecan
      deposition. These results suggest that versican is present as an aggregate
      distinct from the aggrecan aggregate and may play specific roles in the articular
      surface.

PMID- 16648632
TI  - The Swi2/Snf2 bromodomain is required for the displacement of SAGA and the
      octamer transfer of SAGA-acetylated nucleosomes.
AB  - The SWI/SNF and SAGA chromatin-modifying complexes contain bromodomains that help
      anchor these complexes to acetylated promoter nucleosomes. To study the
      importance of bromodomains in these complexes, we have compared the chromatin
      remodeling and octamer-transfer activity of the SWI/SNF complex to a mutant
      complex that lacks the Swi2/Snf2 bromodomain. Here we show that the SWI/SNF
      complex can remodel or transfer SAGA-acetylated nucleosomes more efficiently than
      the Swi2/Snf2 bromodomain-deleted complex. These results demonstrate that the
      Swi2/Snf2 bromodomain is important for the remodeling as well as for the octamer
      transfer activity of the complex on H3-acetylated nucleosomes. Moreover, we show
      that, although the wild-type SWI/SNF complex displaces SAGA that is bound to
      acetylated nucleosomes, the bromodomain mutant SWI/SNF complex is less efficient
      in SAGA displacement. Thus, the Swi2/Snf2 bromodomain is required for the full
      functional activity of SWI/SNF on acetylated nucleosomes and is important for the
      displacement of SAGA from acetylated promoter nucleosomes.

PMID- 16648633
TI  - Hyaluronan oligosaccharides induce matrix metalloproteinase 13 via
      transcriptional activation of NFkappaB and p38 MAP kinase in articular
      chondrocytes.
AB  - Hyaluronan exerts a variety of biological effects on cells including changes in
      cell migration, proliferation, and matrix metabolism. However, the signaling
      pathways associated with the action of hyaluronan on cells have not been clearly
      defined. In some cells, signaling is induced by the loss of cell-hyaluronan
      interactions. The goal of this study was to use hyaluronan oligosaccharides as a
      molecular tool to explore the effects of changes in cell-hyaluronan interactions
      and determine the underlying molecular events that become activated. In this
      study, hyaluronan oligosaccharides induced the loss of extracellular matrix
      proteoglycan and collagen from cultured slices of normal adult human articular
      cartilage. This loss was coincident with an increased expression of matrix
      metalloproteinase (MMP)-13. MMP-13 expression was also induced in articular
      chondrocytes by hyaluronan (HA) hexasaccharides but not by HA tetrasaccharides
      nor high molecular weight hyaluronan. MMP-13 promoter-reporter constructs in CD44
      null COS-7 cells revealed that both CD44-dependent and CD44-independent events
      mediate the induction of MMP-13 by hyaluronan oligosaccharides. Electromobility
      gel shift assays demonstrated the activation of chondrocyte NFkappaB by
      hyaluronan oligosaccharides. NFkappaB activation was also documented in C-28/I2
      immortalized human chondrocytes by luciferase promoter assays and phosphorylation
      of IKK-alpha/beta. The link between activation of NFkappaB and MMP-13 induction
      by HA oligosaccharides was further confirmed through the use of the NFkappaB
      inhibitor helenalin. Inhibition of MAP kinases also demonstrated the involvement
      of p38 MAP kinase in the hyaluronan oligosaccharide induction of MMP-13. Our
      findings suggest that hyaluronan-CD44 interactions affect matrix metabolism via
      activation of NFkappaB and p38 MAP kinase.

PMID- 16648634
TI  - Inhibition of JNK promotes differentiation of epidermal keratinocytes.
AB  - In inflamed tissue, normal signal transduction pathways are altered by
      extracellular signals. For example, the JNK pathway is activated in psoriatic
      skin, which makes it an attractive target for treatment. To define
      comprehensively the JNK-regulated genes in human epidermal keratinocytes, we
      compared the transcriptional profiles of control and JNK inhibitor-treated
      keratinocytes, using DNA microarrays. We identified the differentially expressed
      genes 1, 4, 24, and 48 h after the treatment with SP600125. Surprisingly, the
      inhibition of JNK in keratinocyte cultures in vitro induces virtually all aspects
      of epidermal differentiation in vivo: transcription of cornification markers,
      inhibition of motility, withdrawal from the cell cycle, stratification, and even
      production of cornified envelopes. The inhibition of JNK also induces the
      production of enzymes of lipid and steroid metabolism, proteins of the
      diacylglycerol and inositol phosphate pathways, mitochondrial proteins, histones,
      and DNA repair enzymes, which have not been associated with differentiation
      previously. Simultaneously, basal cell markers, including integrins,
      hemidesmosome and extracellular matrix components, are suppressed. Promoter
      analysis of regulated genes finds that the binding sites for the forkhead family
      of transcription factors are over-represented in the SP600125-induced genes and c
      Fos sites in the suppressed genes. The JNK-induced proliferation appears to be
      secondary to inhibition of differentiation. The results indicate that the
      inhibition of JNK in epidermal keratinocytes is sufficient to initiate their
      differentiation program and suggest that augmenting JNK activity could be used to
      delay cornification and enhance wound healing, whereas attenuating it could be a
      differentiation therapy-based approach for treating psoriasis.

PMID- 16648635
TI  - Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up
      regulation of metalloprotease activity.
AB  - Biometals play an important role in Alzheimer disease, and recent reports have
      described the development of potential therapeutic agents based on modulation of
      metal bioavailability. The metal ligand clioquinol (CQ) has shown promising
      results in animal models and small phase clinical trials; however, the actual
      mode of action in vivo has not been determined. We now report a novel effect of
      CQ on amyloid beta-peptide (Abeta) metabolism in cell culture. Treatment of
      Chinese hamster ovary cells overexpressing amyloid precursor protein with CQ and
      Cu(2+) or Zn(2+) resulted in an approximately 85-90% reduction of secreted Abeta
      (1-40) and Abeta-(1-42) compared with untreated controls. Analogous effects were
      seen in amyloid precursor protein-overexpressing neuroblastoma cells. The
      secreted Abeta was rapidly degraded through up-regulation of matrix
      metalloprotease (MMP)-2 and MMP-3 after addition of CQ and Cu(2+). MMP activity
      was increased through activation of phosphoinositol 3-kinase and JNK. CQ and
      Cu(2+) also promoted phosphorylation of glycogen synthase kinase-3, and this
      potentiated activation of JNK and loss of Abeta-(1-40). Our findings identify an
      alternative mechanism of action for CQ in the reduction of Abeta deposition in
      the brains of CQ-treated animals and potentially in Alzheimer disease patients.

PMID- 16648636
TI  - Role of glutaredoxin-3 and glutaredoxin-4 in the iron regulation of the Aft1
      transcriptional activator in Saccharomyces cerevisiae.
AB  - The transcription factors Aft1 and Aft2 from Saccharomyces cerevisiae regulate
      the expression of genes involved in iron homeostasis. These factors induce the
      expression of iron regulon genes in iron-deficient yeast but are inactivated in
      iron-replete cells. Iron inhibition of Aft1/Aft2 was previously shown to be
      dependent on mitochondrial components required for cytosolic iron sulfur protein
      biogenesis. We presently show that the nuclear monothiol glutaredoxins Grx3 and
      Grx4 are critical for iron inhibition of Aft1 in yeast cells. Cells lacking both
      glutaredoxins show constitutive expression of iron regulon genes. Overexpression
      of Grx4 attenuates wild type Aft1 activity. The thioredoxin-like domain in Grx3
      and Grx4 is dispensable in mediating iron inhibition of Aft1 activity, whereas
      the conserved cysteine that is part of the conserved CGFS motif in monothiol
      glutaredoxins is essential for this function. Grx3 and Grx4 interact with Aft1 as
      shown by two-hybrid interactions and co-immunoprecipitation assays. The
      interaction between glutaredoxins and Aft1 is not modulated by the iron status of
      cells but is dependent on the conserved glutaredoxin domain Cys residue. Thus,
      Grx3 and Grx4 are novel components required for Aft1 iron regulation that most
      likely occurs in the nucleus.

PMID- 16648637
TI  - The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged
      helix domain.
AB  - MAN1 is an integral protein of the inner nuclear membrane that interacts with
      nuclear lamins and emerin, thus playing a role in nuclear organization. It also
      binds to chromatin-associated proteins and transcriptional regulators, including
      the R-Smads, Smad1, Smad2, and Smad3. Mutations in the human gene encoding MAN1
      cause sclerosing bone dysplasias, which sometimes have associated skin
      abnormalities. At the molecular level, these mutations lead to loss of the MAN1-R
      Smads interaction, thus perturbing transforming growth factor beta superfamily
      signaling pathway. As a first step to understanding the physical basis of MAN1
      interaction with R-Smads, we here report the structural characterization of the
      carboxyl-terminal nucleoplasmic region of MAN1, which is responsible for Smad
      binding. This region exhibits an amino-terminal globular domain adopting a winged
      helix fold, as found in several Smad-associated sequence-specific DNA binding
      factors. Consistently, it binds to DNA through the positively charged recognition
      helix H3 of its winged helix motif. However, it does not show the predicted
      carboxyl-terminal U2AF homology domain in solution, suggesting that the folding
      and stability of such a domain in MAN1 depend upon binding to an unidentified
      partner. Modeling the complex between DNA and the winged helix domain shows that
      the regions involved in DNA binding are essentially distinct from those reported
      to be involved in Smad binding. This suggests that MAN1 binds simultaneously to R
      Smads and their targeted DNA sequences.

PMID- 16648638
TI  - Translocator proteins in the two-partner secretion family have multiple domains.
AB  - The two-partner secretion pathway in Gram-negative bacteria consists of a TpsA
      exoprotein and a cognate TpsB outer membrane translocator protein. Previous work
      has demonstrated that the TpsB protein forms a beta-barrel structure with pore
      forming activity and facilitates translocation of the TpsA protein across the
      outer membrane. In this study, we characterized the functional domains of the
      Haemophilus influenzae HMW1B protein, a TpsB protein that interacts with the H.
      influenzae HMW1 adhesin. Using c-Myc epitope tag insertions and cysteine
      substitution mutagenesis, we discovered that HMW1B contains an N-terminal surface
      localized domain, an internal periplasmic domain, and a C-terminal membrane
      anchor. Functional and biochemical analysis of the c-Myc epitope tag insertions
      and a series of HMW1B deletion constructs demonstrated that the periplasmic
      domain is required for secretion of HMW1 and that the C-terminal membrane anchor
      (HMW1B-(234-545)) is capable of oligomerization and pore formation. Similar to
      our observations with HMW1B, examination of a Bordetella pertussis TpsB protein
      called FhaC revealed that the C terminus of FhaC (FhaC-(232-585)) is capable of
      pore formation. We speculate that all TpsB proteins have a modular structure,
      with a periplasmic domain that interacts with the cognate TpsA protein and with
      pore forming activity contained within the C terminus.

PMID- 16648639
TI  - Identification of ligands with bicyclic scaffolds provides insights into
      mechanisms of estrogen receptor subtype selectivity.
AB  - Estrogen receptors alpha (ERalpha) and beta (ERbeta) have distinct functions and
      differential expression in certain tissues. These differences have stimulated the
      search for subtype-selective ligands. Therapeutically, such ligands offer the
      potential to target specific tissues or pathways regulated by one receptor
      subtype without affecting the other. As reagents, they can be utilized to probe
      the physiological functions of the ER subtypes to provide information
      complementary to that obtained from knock-out animals. A fluorescence resonance
      energy transfer-based assay was used to screen a 10,000-compound chemical library
      for ER agonists. From the screen, we identified a family of ERbeta-selective
      agonists whose members contain bulky oxabicyclic scaffolds in place of the planar
      scaffolds common to most ER ligands. These agonists are 10-50-fold selective for
      ERbeta in competitive binding assays and up to 60-fold selective in
      transactivation assays. The weak uterotrophic activity of these ligands in
      immature rats and their ability to stimulate expression of an ERbeta regulated
      gene in human U2OS osteosarcoma cells provides more physiological evidence of
      their ERbeta-selective nature. To provide insight into the molecular mechanisms
      of their activity and selectivity, we determined the crystal structures of the
      ERalpha ligand-binding domain (LBD) and a peptide from the glucocorticoid
      receptor-interacting protein 1 (GRIP1) coactivator complexed with the ligands
      OBCP-3M, OBCP-2M, and OBCP-1M. These structures illustrate how the bicyclic
      scaffolds of these ligands are accommodated in the flexible ligand-binding pocket
      of ER. A comparison of these structures with existing ER structures suggests that
      the ERbeta selectivity of OBCP ligands can be attributed to a combination of
      their interactions with Met-336 in ERbeta and Met-421 in ERalpha. These bicyclic
      ligands show promise as lead compounds that can target ERbeta. In addition, our
      understanding of the molecular determinants of their subtype selectivity provides
      a useful starting point for developing other ER modulators belonging to this
      relatively new structural class.

PMID- 16648641
TI  - Linkage disequilibrium on the bovine X chromosome: characterization and use in
      quantitative trait locus mapping.
AB  - We herein demonstrate that in the Holstein-Friesian dairy cattle population,
      microsatellites are as polymorphic on the X chromosome as on the autosomes but
      that the level of linkage disequilibrium between these markers is higher on the X
      chromosome than on the autosomes. The latter observation is not compatible with
      the small male-to-female ratio that prevails in this population and results in a
      higher gonosomal than autosomal effective population size. It suggests that the X
      chromosome undergoes distinct selective or mutational forces. We describe and
      characterize a novel Markovian approach to exploit this linkage disequilibrium to
      compute the probability that two chromosomes are identical-by-descent conditional
      on flanking marker data. We use the ensuing probabilities in a restricted maximum
      likelihood approach to search for quantitative trait loci (QTL) affecting 48
      traits of importance to the dairy industry and provide evidence for the presence
      of QTL affecting 5 of these traits on the bovine X chromosome.

PMID- 16648640
TI  - Analysis of close stable homolog juxtaposition during meiosis in mutants of
      Saccharomyces cerevisiae.
AB  - A unique aspect of meiosis is the segregation of homologous chromosomes at the
      meiosis I division. The pairing of homologous chromosomes is a critical aspect of
      meiotic prophase I that aids proper disjunction at anaphase I. We have used a
      site-specific recombination assay in Saccharomyces cerevisiae to examine allelic
      interaction levels during meiosis in a series of mutants defective in
      recombination, chromatin structure, or intracellular movement. Red1, a component
      of the chromosome axis, and Mnd1, a chromosome-binding protein that facilitates
      interhomolog interaction, are critical for achieving high levels of allelic
      interaction. Homologous recombination factors (Sae2, Rdh54, Rad54, Rad55, Rad51,
      Sgs1) aid in varying degrees in promoting allelic interactions, while the Srs2
      helicase appears to play no appreciable role. Ris1 (a SWI2/SNF2 related protein)
      and Dot1 (a histone methyltransferase) appear to play minor roles. Surprisingly,
      factors involved in microtubule-mediated intracellular movement (Tub3, Dhc1, and
      Mlp2) appear to play no appreciable role in homolog juxtaposition, unlike their
      counterparts in fission yeast. Taken together, these results support the notion
      that meiotic recombination plays a major role in the high levels of homolog
      interaction observed during budding yeast meiosis.

PMID- 16648642
TI  - Fitness benefits of systemic acquired resistance during Hyaloperonospora
      parasitica infection in Arabidopsis thaliana.
AB  - We investigated the fitness benefits of systemic acquired resistance (SAR) in
      Arabidopsis thaliana using a mutational and transformational genetic approach.
      Genetic lines were designed to differ in the genes determining resistance
      signaling in a common genetic background. Two mutant lines (cpr1 and cpr5)
      constitutively activate SAR at different points in SAR signaling, and one mutant
      line (npr1) has impaired SAR. The transgenic line (NPR1-H) has enhanced
      resistance when SAR is activated, but SAR is still inducible similarly to wild
      type. The fitness benefits were also investigated under two nutrient levels to
      test theories that preventing pathogen damage and realized resistance benefits
      may be affected by nutrient availability. Under low-nutrient conditions and
      treatment with the pathogenic oomycete, Hyaloperonospora parasitica, wild type
      had a higher fitness than the mutant that could not activate SAR, demonstrating
      that normal inducible SAR is beneficial in these conditions; this result,
      however, was not found under high-nutrient conditions. The mutants with
      constitutive SAR all failed to show a fitness benefit in comparison to wild type
      under a H. parasitica pathogen treatment, suggesting that SAR is induced to
      prevent an excessive fitness cost.

PMID- 16648643
TI  - Genetic interactions between TFIIF and TFIIS.
AB  - The eukaryotic transcript elongation factor TFIIS is encoded by a nonessential
      gene, PPR2, in Saccharomyces cerevisiae. Disruptions of PPR2 are lethal in
      conjunction with a disruption in the nonessential gene TAF14/TFG3. While
      investigating which of the Taf14p-containing complexes may be responsible for the
      synthetic lethality between ppr2Delta and taf14Delta, we discovered genetic
      interactions between PPR2 and both TFG1 and TFG2 encoding the two larger subunits
      of the TFIIF complex that also contains Taf14p. Mutant alleles of tfg1 or tfg2
      that render cells cold sensitive have improved growth at low temperature in the
      absence of TFIIS. Remarkably, the amino-terminal 130 amino acids of TFIIS, which
      are dispensable for the known in vitro and in vivo activities of TFIIS, are
      required to complement the lethality in taf14Delta ppr2Delta cells. Analyses of
      deletion and chimeric gene constructs of PPR2 implicate contributions by
      different regions of this N-terminal domain. No strong common phenotypes were
      identified for the ppr2Delta and taf14Delta strains, implying that the proteins
      are not functionally redundant. Instead, the absence of Taf14p in the cell
      appears to create a dependence on an undefined function of TFIIS mediated by its
      N-terminal region. This region of TFIIS is also at least in part responsible for
      the deleterious effect of TFIIS on tfg1 or tfg2 cold-sensitive cells. Together,
      these results suggest a physiologically relevant functional connection between
      TFIIS and TFIIF.

PMID- 16648644
TI  - The Drosophila Nbs protein functions in multiple pathways for the maintenance of
      genome stability.
AB  - The Mre11/Rad50/Nbs (MRN) complex and the two protein kinases ATM and ATR play
      critical roles in the response to DNA damage and telomere maintenance in
      mammalian systems. It has been previously shown that mutations in the Drosophila
      mre11 and rad50 genes cause both telomere fusion and chromosome breakage. Here,
      we have analyzed the role of the Drosophila nbs gene in telomere protection and
      the maintenance of chromosome integrity. Larval brain cells of nbs mutants
      display telomeric associations (TAs) but the frequency of these TAs is lower than
      in either mre11 or rad50 mutants. Consistently, Rad50 accumulates in the nuclei
      of wild-type cells but not in those of nbs cells, indicating that Nbs mediates
      transport of the Mre11/Rad50 complex in the nucleus. Moreover, epistasis analysis
      revealed that rad50 nbs, tefu (ATM) nbs, and mei-41 (ATR) nbs double mutants have
      significantly higher frequencies of TAs than either of the corresponding single
      mutants. This suggests that Nbs and the Mre11/Rad50 complex play partially
      independent roles in telomere protection and that Nbs functions in both ATR- and
      ATM-controlled telomere protection pathways. In contrast, analysis of chromosome
      breakage indicated that the three components of the MRN complex function in a
      single pathway for the repair of the DNA damage leading to chromosome
      aberrations.

PMID- 16648645
TI  - The molecular identities of the Caenorhabditis elegans intraflagellar transport
      genes dyf-6, daf-10 and osm-1.
AB  - The Caenorhabditis elegans genes dyf-6, daf-10, and osm-1 are among the set of
      genes that affect chemotaxis and the ability of certain sensory neurons to take
      up fluorescent dyes from the environment. Some genes in this category are known
      to be required for intraflagellar transport (IFT), which is the bidirectional
      movement of raft-like particles along the axonemes of cilia and flagella. The
      cloning of dyf-6, daf-10, and osm-1 are described here. The daf-10 and osm-1 gene
      products resemble each other and contain WD and WAA repeats. DYF-6, the product
      of a complex locus, lacks known motifs, but orthologs are present in flies and
      mammals. Phenotypic analysis of dyf-6 mutants expressing an OSM-6::GFP reporter
      indicates that the cilia of the amphid and phasmid dendritic endings are
      foreshortened. Consistent with genetic mosaic analysis, which indicates that dyf
      6 functions in neurons of the amphid sensilla, DYF-6::GFP is expressed in amphid
      and phasmid neurons. Movement of DYF-6::GFP within the ciliated endings of the
      neurons indicates that DYF-6 is involved in IFT. In addition, IFT can be observed
      in dauer larvae.

PMID- 16648646
TI  - Heterochromatic genes in Drosophila: a comparative analysis of two genes.
AB  - Centromeric heterochromatin comprises approximately 30% of the Drosophila
      melanogaster genome, forming a transcriptionally repressive environment that
      silences euchromatic genes juxtaposed nearby. Surprisingly, there are genes
      naturally resident in heterochromatin, which appear to require this environment
      for optimal activity. Here we report an evolutionary analysis of two genes, Dbp80
      and RpL15, which are adjacent in proximal 3L heterochromatin of D. melanogaster.
      DmDbp80 is typical of previously described heterochromatic genes: large, with
      repetitive sequences in its many introns. In contrast, DmRpL15 is
      uncharacteristically small. The orthologs of these genes were examined in D.
      pseudoobscura and D. virilis. In situ hybridization and whole-genome assembly
      analysis show that these genes are adjacent, but not centromeric in the genome of
      D. pseudoobscura, while they are located on different chromosomal elements in D.
      virilis. Dbp80 gene organization differs dramatically among these species, while
      RpL15 structure is conserved. A bioinformatic analysis in five additional
      Drosophila species demonstrates active repositioning of these genes both within
      and between chromosomal elements. This study shows that Dbp80 and RpL15 can
      function in contrasting chromatin contexts on an evolutionary timescale. The
      complex history of these genes also provides unique insight into the dynamic
      nature of genome evolution.

PMID- 16648647
TI  - The Drosophila boundary element-associated factors BEAF-32A and BEAF-32B affect
      chromatin structure.
AB  - Binding sites for the Drosophila boundary element-associated factors BEAF-32A and
      -32B are required for the insulator activity of the scs' insulator. BEAF binds to
      hundreds of sites on polytene chromosomes, indicating that BEAF-utilizing
      insulators are an important class in Drosophila. To gain insight into the role of
      BEAF in flies, we designed a transgene encoding a dominant-negative form of BEAF
      under GAL4 UAS control. This BID protein encompasses the BEAF self-interaction
      domain. Evidence is provided that BID interacts with BEAF and interferes with
      scs' insulator activity and that BEAF is the major target of BID in vivo. BID
      expression during embryogenesis is lethal, implying that BEAF is required during
      early development. Expression of BID in eye imaginal discs leads to a rough-eye
      phenotype, and this phenotype is rescued by a third copy of the BEAF gene.
      Expression of BID in salivary glands leads to a global disruption of polytene
      chromatin structure, and this disruption is largely rescued by an extra copy of
      BEAF. BID expression also enhances position-effect variegation (PEV) of the
      w(m4h) allele and a yellow transgene inserted into the pericentric
      heterochromatin of chromosome 2R, while a third copy of the BEAF gene suppresses
      PEV of both genes. These results support the hypothesis that BEAF-dependent
      insulators function by affecting chromatin structure or dynamics.

PMID- 16648648
TI  - Endurance exercise and leg strength in older women.
AB  - Quadriceps strength and mass peak in the third decade of life, plateau, and then
      decline from the fifth decade on. To examine the influence of chronic endurance
      training and age on lean mass and leg strength, women runners (n = 62, age 43-69
      years) and sedentary participants (n = 33, age 43-66 years) were divided into 40
      , 50-, and 60-year age groups. Absolute isokinetic concentric torque did not
      differ between runners and sedentary women (97.9 +/- 19.5 and 104.6 +/- 22.7 N .
      m, respectively, p = .18) but was different between age groups independent of
      exercise status (107.6 +/- 18.4, 97.1 +/- 19.9, and 90.1 +/- 21.4 N . m, for 40s,
      50s, and 60s, respectively, p < .05). Lean body mass also differed by age group
      (p < .05) but did not change differently among runners and sedentary women. These
      findings suggest that chronic endurance training might not influence the loss of
      muscle mass and muscle strength that occur with aging.

PMID- 16648649
TI  - The association between mood states and physical activity in postmenopausal,
      obese, sedentary women.
AB  - Mood states influence evaluative judgments that can affect the decision to
      exercise or to continue to exercise. This study examined how mood associated with
      graded exercise testing (GXT) in sedentary, obese, postmenopausal women (N = 25)
      was associated with physical activity and predicted VO2max during and after a
      behavioral weight-loss program (BWLP). Measures of physical activity included
      planned exercise, calories from physical activity, leisure-time physical
      activity, and predicted VO2max. Mood before and after pre-BWLP GXT was assessed
      using the Profile of Mood States. Mood before and after the GXT was more strongly
      associated with planned exercise than other forms of physical activity, and this
      effect became stronger over time. Mood enhancement in response to exercise was
      not related to physical activity. Mood before and after exercise might yield
      important clinical information that can be used to promote physical activity in
      sedentary adults.

PMID- 16648650
TI  - Older women's cardiovascular responses to deep-water running.
AB  - The aim of the study was to examine submaximal and maximal physiological
      responses and perceived exertion during deep-water running with a vest compared
      with the responses during treadmill running in healthy elderly women. Eleven
      healthy women 70 +/- 2 years old participated. On two different occasions they
      performed a graded maximal exercise test on a treadmill on land and a graded
      maximal exercise test in water wearing a vest. At maximal work the oxygen uptake
      was 29% lower (p < .05), the heart rate was 8% lower (p < .05), and the
      ventilation was 16% lower (p < .05) during deep-water running than during
      treadmill running. During submaximal absolute work the heart rate was higher
      during deep-water running than during treadmill running for the elderly women.
      The participants had lower maximal oxygen uptake, heart rate, ventilation,
      respiratory-exchange ratio, and rate of perceived exertion during maximal deep
      water running with a vest than during maximal treadmill running. These responses
      were, however, higher during submaximal deep-water running than during treadmill
      running.

PMID- 16648651
TI  - Comparison of exercise attitudes and behaviors of urban older adults with AARP's
      national sample results.
AB  - This study assessed perceptions about exercise among a convenience sample of low
      income, urban, older adult patients at a publicly operated ambulatory primary
      care clinic, and results were then compared with the findings of a national
      study. Although it was expected that the predominantly minority and economically
      disadvantaged participants in this study would trail significantly behind their
      White counterparts in their perceptions and behavior regarding exercise, findings
      demonstrated otherwise. Specifically, when physicians encourage moderate
      exercise, when patients believe that they can overcome barriers to exercise, and
      when the environment supports moderate exercise through the availability of
      community exercise classes, inequities in health behaviors can be reduced.
      Interventions designed to increase exercise for this population should be
      developed with an understanding of the many barriers that they will have to
      overcome, a focus on building confidence, and communicating the many benefits of
      this behavior.

PMID- 16648652
TI  - The effects of strength training on memory in older adults.
AB  - The authors examined whether resistance training has an effect on working memory
      span. Participants included 210 community-residing older adults with at least one
      disability from the Strong for Life program, a randomized controlled trial that
      examined the effects of home-based resistance exercise. Memory was assessed with
      the WAIS backward digit span at baseline and 3 and 6 months into the
      intervention. Although there were no differences between the experimental
      treatment and control groups in average levels of memory change, within the
      treatment group change in resistance level during the intervention was a
      significant predictor of memory change, controlling for age, education, sex, and
      disability level. The results suggest that strength training can benefit memory
      among older adults, especially when using higher resistance levels.

PMID- 16648653
TI  - The effect of aging and tennis playing on coincidence-timing accuracy.
AB  - This study examined the effect of tennis playing on the coincidence timing (CT)
      of older adults. Young, younger-old and older-old (20-30, 60-69, and 70-79 years
      old, respectively) tennis players and nonplayers were asked to synchronize a
      simple response (pressing a button) with the arrival of a moving stimulus at a
      target. Results showed that the older tennis players responded with a slight bias
      similar to that of the young players. Two experiments were conducted to determine
      whether the elimination of age effects through tennis playing was a result of
      maintaining basic perceptuomotor and perceptual processes or of some possible
      compensation strategy. The results revealed that the age-related increase in the
      visuomotor delay was significantly correlated with CT performance in older
      nonplayers but not in older tennis players. These results suggest that playing
      tennis is beneficial to older adults, insofar as they remained as accurate as
      younger ones despite less efficient perceptuomotor processes. This supports the
      compensation hypothesis.

PMID- 16648654
TI  - Comparison of two methods of measuring physical activity in South African older
      adults.
AB  - The aim of this study was to assess the validity and reliability of the Yale
      Physical Activity Survey (YPAS) and the short version of the International
      Physical Activity Questionnaire (IPAQ) in older South African adults. The YPAS
      includes measures of weekly energy expenditure (EE) for housework, yard work,
      caregiving, exercise, and recreation. The IPAQ measures total time and EE during
      vigorous and moderate activity, walking, and sitting. The instruments were
      administered twice for test-retest reliability (men, n = 52, 68 +/- 5.4 years,
      and women, n = 70, 66 +/- 5.8 years). Data for criterion validity were obtained
      from accelerometers. YPAS reliability ranged from r = .44 to.80 for men and r =
      .59 to .99 for women (p < .0001). IPAQ reliability was lower for men (r = .29 to
      .76) than for women (r = .46 to .77). Criterion validity of the YPAS was .31 to
      .54 for men and .26 to .29 for women. The YPAS and short IPAQ had comparable
      results for reliability and criterion validity.

PMID- 16648655
TI  - Relationship of Helicobacter pylori to Bcl-2 family expression, DNA content, and
      pathological characteristics of gastric cancer.
AB  - BACKGROUND: Despite the fact that the association of Helicobacter pylori with an
      increased risk of gastric cancer has been well documented, the exact mechanisms
      of this association have not been fully elucidated. Scarce data on H. pylori
      infection and its relationship with the different pathological characteristics
      are available in Egypt. AIM OF THE STUDY: The rationale of the present study was
      to determine the prevalence of H. pylori in a group of gastric cancer patients
      and to analyze the relationship between H. pylori infection with the different
      pathological characteristics including the types of gastric cancer and tumor
      location within the stomach, in addition, to investigate the Bcl-2 and Bax
      expressions along with DNA flow cytometric analysis in the gastric cancer
      patients with and without H. pylori infection. METHODS: Samples were obtained
      from 66 consecutive patients with gastric cancer (46 males and 20 females). The
      youngest patient was 20 yr old, the oldest 76 yr with mean age of 52.8 yr. The
      samples were subjected for histopathological characterization, H. pylori
      detection, DNA flow cytometric analysis, and Bcl-2 and Bax expressions detection,
      in addition to apoptosis analysis. RESULTS: The obtained results showed that the
      H. pylori infection was found in 38/66 (57.6%) [Odds ratio=1.357 with 95%
      confidence interval (CI) 0.84-2.2]. There was a statistical significance for Bcl
      2, Bax, and apoptosis with H. pylori status (p = 0.009, 0.008, 0.032,
      respectively). On the other hand, There was a statistical significance for H.
      pylori infection with the disease grade (p = 0.015) and lymph node metastasis (p
      = 0.05). No statistical significance was found between H. pylori status with the
      patients' age, gender, tumor site, tumor type, depth of invasion, and stromal
      reaction. CONCLUSIONS: These data may indicate that the H. pylori infection not
      only contributes in the disease formation through the apoptosis dysregulation but
      also takes a part in the disease dissemination and progression. In addition, it
      may reflect a biologic, pathogenic, and ethnic background affecting the
      relationship of H. pylori infection to gastric cancer in the Egyptian patients. A
      high rate of smoking in Egypt and the diet are important factors that may affect
      such background. Further studies are warranted.

PMID- 16648656
TI  - Comparison of clinical stage, therapy response, and patient outcome between
      squamous cell carcinoma and adenocarcinoma of the esophagus.
AB  - PURPOSE: To analyze the differences in clinical stage, pathologic response to
      chemoradiotherapy, patterns of failure, and overall survival (OS) between
      patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the
      esophagus. PATIENTS AND METHODS: We stratified patients by two histologies, ACA
      and SCC, and statistically compared their clinical stage, post-therapy pathologic
      response, patterns of failure, and OS. RESULTS: Of the 235 patients who underwent
      preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the
      ACA patients, a significantly larger proportion was male (93% vs 7%; p <0.001),
      whereas sex was distributed similarly among SCC patients (55% male vs 45% female;
      p = 0.5). A significantly larger percentage of SCC patients were classified as
      lower TN and overall stage than ACA patients (T2 = 41% vs 28%, p <0.0001; N0 =
      69% vs 48%, p = 0.01; stage II = 76% vs 55%, p <0.001). A significantly greater
      portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p =
      0.02). Among the pathCR patients in clinical stage II, there were significantly
      greater proportion of SCC patients (77% vs 63%; p <0.001) than ACA patients.
      Among the pathCR patients in clinical stage III patients, a significantly greater
      proportion were ACA patients (38% vs 23%; p <0.001) than SCC patients. The median
      and 5-yr OS was 53 +/- 11 mo and 39% for ACA patients and 35 +/- 14 mo and 37%
      for SCC (median OS, p = 0.3). Among pathCR patients, median OS of ACA patients
      (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p =
      0.07); results were similar for non-pathCR patients. DFS results were similar in
      all subgroups. Among the whole cohort, incidence of local-regional recurrence and
      distant metastases did not vary significantly. The median time to distant
      metastases did not vary significantly for pathCR and non-pathCR patients.
      CONCLUSIONS: We believe this is the first study that compares failure outcome of
      ACA and SCC patients with similar clinical stage after trimodality therapy. Our
      data suggest that significant differences in clinical stage and post-therapy
      pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes
      in the resected specimens of ACA patients resulted in a shorter time-to
      metastases suggesting that ACA patients need better systemic control.

PMID- 16648657
TI  - Four peptides decrease human colon adenocarcinoma cell number and DNA synthesis
      via cyclic GMP.
AB  - BACKGROUND: Mortality from colon cancer is significant with an expected 30,350
      colon cancer deaths in 2005 with current treatment(s). Long-acting natriuretic
      peptide, vessel dilator, kaliuretic peptide, and atrial natriuretic peptide have
      significant anticancer effects in breast and pancreatic adenocarcinomas. AIM OF
      STUDY: Whether these peptide hormones have anticancer effects in colon
      adenocarcinoma cells and whether these effects are specifically mediated by
      cyclic GMP has not been determined. METHODS: These peptide hormones were
      evaluated for anticancer effects in human colon adenocarcinoma cells and to
      determine whether their anticancer effects are specifically mediated by cyclic
      GMP. RESULTS: There was a 89-97% decrease (p <0.001 for each) in colon
      adenocarcinoma cells within 24 h with 1 mM of these peptide hormones. There was a
      significant (p <0.05) decrease in human colon cancer cell number with each 10
      fold increase in concentration from 1 to 1,000 microM (i.e., 1 mM) of these four
      peptide hormones without any proliferation in the 3 d following this decrease.
      These same hormones decreased DNA synthesis 65-83% (p <0.001). Cyclic GMP
      antibody inhibited 75- 80% of these peptides' ability to decrease colon
      adenocarcinoma cell number and inhibited 92-96% of their DNA synthesis effects
      and 97% of cyclic GMP's effects. Western blots revealed that for the first time
      natriuretic peptide receptors (NPR) A and C were present in colon adenocarcinoma
      cells. CONCLUSIONS: Four peptide hormones eliminate up to 97% of colon cancer
      cells within 24 h with their DNA effects specifically mediated by cyclic GMP.

PMID- 16648658
TI  - Deteriorating stage profile of gastrointestinal cancer in Finland.
AB  - BACKGROUND: The prognosis of patients with gastrointestinal (GI) cancer is mainly
      due to the stage of the tumor at the diagnosis. Regardless of several innovations
      in diagnostic and therapeutic gastroenterology, there is no longitudinal data of
      the trends of stage profile of patients with gastrointestinal cancer in Finland.
      AIM: To study the incidence by stage of GI cancer in Finland in the past 15 yr in
      the entire country as well as in two subpopulations with different population
      profile: in a population with a small number of residents over 65 yr of age
      (Jorvi district) and in a population with a large number of residents over 65 yr
      of age (Kanta-Hame district). METHODS: The hospital discharge records of patients
      with upper or lower GI cancer between 1986 and 2000 were evaluated in Finland as
      well as in Jorvi and Kanta-Hame hospital districts. The data were obtained from
      the National Research and Development Centre for Welfare and Health, from the
      Centre of Statistics and from the Finnish Cancer Registry. RESULTS: The relative
      incidence of a localized esophagogastric cancer against more severe stages
      decreased from 37.9% to 29.3% in the entire country, from 40.8% to 19.1% in Kanta
      Hame, and from 44.2% to 33.3% in Jorvi area. Respectively, the relative incidence
      of localized colorectal cancer decreased from 53.6% to 48.0% in the entire
      country, from 49.7% to 42.5% in Kanta-Hame, and from 54.5% to 48.4% in Jorvi
      area. CONCLUSIONS: During the past 15 yr the incidence by stage of both upper and
      lower GI cancer is deteriorating in the entire country as well as in areas with
      low and high percentage of residents over 65 yr of age indicating the increase of
      the more severe cases. The deterioration has become more pronounced in the 1990s,
      which requires a careful scrutiny of the function of primary diagnostic services.

PMID- 16648659
TI  - Early colon cancer detected by 18F-FDG PET.
AB  - Positron emission tomography (PET) is a noninvasive functional imaging modality
      that can disclose the presence of a malignant disease. It has recently been
      reported that PET may be useful to detect primary colorectal cancer (CRC). We
      present the case of a 47-yr-old man with early colon cancer detected by 18F
      fluorodeoxyglucose (FDG) PET. The patient consulted us because of a positive
      fecal occult blood test and focal FDG uptake in the pelvic cavity detected at a
      physical check-up. After the usual work up, he was diagnosed as having a sigmoid
      polyp, 16 mm in diameter. Subsequently, colonoscopic polypectomy was carried out.
      The surgical specimen was histologically diagnosed as a well-differentiated
      adenocarcinoma, invading the submucosal layer with lymphatic invasion. Therefore,
      the involved portion of the sigmoid colon was laparoscopically resected. The FDG
      PET carried out 1 yr after the operation, showed no abnormal FDG uptake. PET can
      noninvasively detect an early colon cancer as small as in our patient, as well as
      other cancers in the whole body. Therefore, we consider it suitable as a
      screening examination.

PMID- 16648660
TI  - A case of primary gastric small cell carcinoma with a rare pattern of lymph node
      metastasis.
AB  - We report a very rare case of primary gastric small cell carcinoma (GSCC) that
      was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an
      elevated tumor with a central ulceration in the middle stomach. The patient
      underwent a distal gastrectomy with lymph node dissection. The pathological
      examination showed two separated lesions of the stomach, which contained the
      components of primary GSCC and primary gastric tubular adenocarcinoma.
      Immunohistochemical (IHC) examination demonstrated that the tumor cells in the
      small cell carcinoma stained positive for synaptophysin, chromogranin A, and
      neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells
      independently metastasized to each regional lymph node. Further studies on the
      biological behavior of individual tumors may allow the development of new
      treatment strategies for GSCC.

PMID- 16648661
TI  - Primary malignant fibrous histiocytoma of the small bowel: a report of an
      additional case in duodenum.
AB  - AIMS: We report herein an additional case of primary malignant fibrous
      histiocytoma (MFH) in the duodenum and provide a review of the existing
      literature. METHODS AND RESULTS: A 61-yr-old Chinese man was admitted to our
      hospital with symptoms of melena, anorexia, and weight loss. An abdominal
      computed tomography (CT) and gastrointestinal barium meal examination
      demonstrated a tumor of the duodenum suggestive of primary malignancy. The tumor
      was successfully treated by pancreaticoduodenectomy. It was histopathologically
      and immunohistochemically diagnosed to be a storiform-type primary MFH of the
      duodenum. There have been a total of 40 cases of primary malignant fibrous
      histiocytoma of the small bowel documented in the literature including our
      Chinese cases. CONCLUSION: Primary malignant fibrous histiocytoma of the small
      bowel, especially in the duodenum is extremely rare. The final diagnosis is made
      only after pathological and immunopathological examination of the tumor. The
      malignant potential of such tumors is high. The prognosis may be mainly dependent
      on the invasion and metastasis of tumor, while tumor size is irrelevant. The
      treatment should be surgery if possible. Early surgical intervention may be the
      best form of management that may offer the patient good result.

PMID- 16648662
TI  - Small follicular lymphoma arising near the ampulla of vater: a distinct subtype
      of duodenal lymphoma?
AB  - A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of
      nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in
      diameter adjacent to the duodenal papilla, the surface of which was uneven and
      covered with whitish granules. Based on the results of histological examination
      with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein,
      negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was
      established. Systemic staging examinations suggested the lymphoma was restricted
      to the mucosa and superficial portion of the submucosa in the duodenal wall. The
      patient was treated with a combination of CHOP chemotherapy (cyclophosphamide,
      doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody
      (rituximab), in addition to radiotherapy. After six courses of this combination
      chemotherapy, complete regression of the lymphoma was observed. Although reports
      of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are
      extremely rare, the features of this case are characteristic of small duodenal
      lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular
      type, occurrence in a women, occurrence in the fourth decade of life, and
      favorable outcome, and this type of tumor may need to be distinguished by
      pathogenesis and clinical behavior from various other gastrointestinal lymphomas.

PMID- 16648663
TI  - Merkel cell-nerve cell interaction undergoes formation of a synapse-like
      structure in a primary culture.
AB  - Merkel cells have been assumed to guide nerve fibers to the skin. However, there
      has been little in vitro evidence that supports this hypothesis, because there is
      no suitable established culture system of Merkel cells. Here we show that Merkel
      cells isolated from rat footpad skin were successfully cultured in a monolayer
      with keratinocytes. Keratinocytes did not affect any structural changes in Merkel
      cells. When nerve cells (NG108-15 or PC12) were added to the culture system, both
      nerve fibers and cytoplasmic processes of Merkel cells outgrew and cooperatively
      organized synapse-like structures at their contact points. Nerve cells promoted
      Merkel cell survival, compared with keratinocytes only. Merkel cell proliferation
      was not detected in all conditions, even with nerve growth factor, neurotrophin
      3, interleukin-6 and tumor necrosis factor-alpha. The data suggest, firstly, that
      Merkel cells may guide nerve fibers to the skin by interacting with nerve cells;
      and, secondly, that nerve cells, but not keratinocytes, may produce some survival
      factors other than the cytokines above for Merkel cells, although Merkel cells
      may be a terminally differentiated cell type. Our method could open a way to
      study Merkel cell biology.

PMID- 16648664
TI  - Cyclic ADP-ribose requires FK506-binding protein to regulate intracellular Ca2+
      dynamics and catecholamine release in acetylcholine-stimulated bovine adrenal
      chromaffin cells.
AB  - The present study was undertaken to elucidate whether cyclic ADP-ribose (cADPR)
      mediates the amplification of Ca2+ signaling and catecholamine release via the
      involvement of FK506-binding proteins (FKBPs)/ryanodine receptor (RyR) in bovine
      adrenal chromaffin cells. cADPR induced Ca2+ release in digitonin-permeabilized
      chromaffin cells and this was blocked by FK506 and rapamycin, ligands for FKBPs;
      8Br-cADPR, a competitive antagonist for cADPR; and antibody for FKBP12/12.6,
      while it was enhanced by cyclosporin A. Ryanodine-induced Ca2+ release was not
      affected by 8Br-cADPR and was remarkably enhanced by FK506, rapamycin,
      cyclosporin A, and cADPR. FK506 binds to FKBP12.6 and removes it from RyRs, but
      cADPR did not affect the binding between FKBP12.6 and RyR. In intact chromaffin
      cells, 8Br-cADPR, FK506, and rapamycin, but not cyclosporin A attenuated the
      sustained intracellular free Ca2+ concentration ([Ca2+]i) rise induced by
      acetylcholine (ACh). 8Br-cADPR, FK506, and SK&F 96365 reduced the Mn2+ entry
      stimulated with ACh only when Ca2+ was present in the extracellular medium. 8Br
      cADPR, FK506, and rapamycin concentration-dependently inhibited the ACh-induced
      catecholamine (CA) release. Here, we present evidence that FKBP12.6 associated
      with RyR may be required for Ca2+ release induced by cADPR in bovine adrenal
      chromaffin cells. cADPR-mediated Ca2+ release from endoplasmic reticulum in ACh
      stimulated chromaffin cells is coupled with Ca2+ influx through the plasma
      membrane which is essential for ACh-stimulated CA release.

PMID- 16648665
TI  - Recent advances in molecular pharmacology of the histamine systems: organic
      cation transporters as a histamine transporter and histamine metabolism.
AB  - Histamine is inactivated by the histamine-metabolizing enzyme histamine N
      methyltransferase (HNMT) in bronchus, kidney, and the central nervous system.
      HNMT seems to be localized in the cytoplasm, but histamine is unable to easily
      enter the intracellular space. Therefore, two hypotheses can be elicited: one is
      the plasma membrane hypothesis that HNMT can be translocated to the plasma
      membrane and function at the cell surface under growth factor stimulation and the
      other is the transporter hypothesis that organic cation transporter (OCT)-2 and 
      3 can function as a histamine transporter as well. To investigate the involvement
      of OCT2, HEK293 cells stably double transfected with C-terminal hemagglutinin
      (HA)-tagged HNMT cDNA and/or C-terminal myc-tagged rat OCT2 were prepared for
      analysis of HNMT activity associated with OCT2 function. After 60-min incubation
      of these cells with PBS including HA (100 microM), N(tau)-methylhistamine (MHA)
      concentration of the supernatants was determined by the HPLC-fluorometry method.
      MHA from cells with HNMT plus OCT-2 was produced at about 3-fold higher level
      than that from cells with HNMT alone, suggesting that OCT-2 could function as a
      histamine transporter as well and that HNMT function could partly depend on OCT-2
      transporter activity. Using OCT-3 knockout (OCT-3-/-) mice, histamine content and
      survival rates were investigated in lipopolysaccharide (LPS)-induced endotoxemia
      model. Without LPS stimulation, histamine content was compared between OCT-3-/-
      and wild mice. Histamine content in the spleen of OCT-3-/- mice was higher than
      that f wild mice. With LPS stimulation, the survival rate of OCT-3-/- mice was
      significantly decreased 12 h after LPS (20 mg/kg) stimulation, suggesting that
      before immunological stimulation, a higher content of histamine in spleen could
      stimulate histamine receptors in mast cells, macrophages, dendritic cells, as
      well as T lymphocytes and explaining the decreased survival rate in OCT-3-/- mice
      possibly due to the functional changes of immunological cells.

PMID- 16648666
TI  - Recent advances in molecular pharmacology of the histamine systems: immune
      regulatory roles of histamine produced by leukocytes.
AB  - Accumulating evidence has highlighted the importance of histamine in immune
      responses. The H1 receptor is involved not only in allergic inflammatory
      reactions but also in augmentation of helper T cell (Th)1 responses, whereas H2
      receptor suppresses Th responses and participates in immune tolerance through
      interleukin-10 and transforming growth factor-beta. Identification of the H4
      receptor, which binds to histamine with high affinity and of which expression is
      limited to the hematopoietic system, has enhanced the importance of histamine in
      immune responses. However, since a majority of previous studies has evaluated the
      effects of exogenous histamine, it remains largely unknown how endogenously
      produced histamine is involved in regulation of such kinds of immune responses.
      Insight into precise roles of histamine in the immune system can not be obtained
      without correct understanding of both the predominance of a certain type of
      histamine receptor and the regulation of histamine synthesis. Here we review a
      part of the recent progress in histamine research in the field of immunology with
      attention to the source of involved histamine.

PMID- 16648667
TI  - Recent advances in molecular pharmacology of the histamine systems: physiology
      and pharmacology of histamine H3 receptor: roles in feeding regulation and
      therapeutic potential for metabolic disorders.
AB  - Histamine H3 receptors (H3Rs) are autoreceptors that negatively regulate the
      release of histamine and other neurotransmitters such as norepinephrine,
      dopamine, and acetylcholine in the central nervous system (CNS). Consistent with
      the wide-spread projection of histaminergic neurons from the lateral
      hypothalamus, H3Rs are widely distributed in the CNS and are believed to play a
      variety of physiological roles, including regulation of feeding, arousal,
      cognition, pain, and endocrine systems. To further understand the physiological
      roles of H3Rs in vivo, we produced H3R knockout (H3R-/-) mice and found that H3R
      /- mice displayed hyperphagia and late-onset obesity associated with
      hyperinsulinemia and leptinemia, the fundamental marks of metabolic syndromes. A
      series of non-imidazole H3R antagonists/inverse agonists with improved
      selectivity and potency have been developed and were found to regulate feeding
      and body weight gain in laboratory animals. Taken together, these observations
      suggest that H3Rs are involved in the regulation of feeding behavior and body
      weight. Several H3R inverse agonists targeting cognitive disorders and dementia
      have entered clinical trials. These trials will give critical information about
      the physiological functions of H3Rs in humans.

PMID- 16648668
TI  - Recent advances in molecular pharmacology of the histamine systems: roles of C
      terminal tails of histamine receptors.
AB  - G-protein-coupled receptors (GPCR) represent a large and diverse superfamily of
      integral membrane proteins to which histamine receptors belong. Increasing
      numbers of proteins have been identified to interact with the C-termini of GPCRs.
      These interactions are implicated in targeting, trafficking, and fine-tuning of
      signaling of GPCRs. Although the C-terminus of the histamine H2 receptor has been
      suggested to play in agonist-induced internalization of the receptor, roles of
      the C-termini of the other three histamine receptors are not known. To date,
      there is no protein identified to interact with the C-termini of histamine
      receptors.

PMID- 16648669
TI  - Recent advances in molecular pharmacology of the histamine systems: regulation of
      histamine H1 receptor signaling by changing its expression level.
AB  - Histamine H1 receptor (H1R) signaling is regulated by changing its expression
      level. Two mechanisms are involved in this regulation. One is down-regulation
      through receptor desensitization. Receptor phosphorylation seemed crucial because
      stimulation of the mutant H1R lacking five putative phosphorylation sites did not
      show down-regulation. The phosphorylation level of the mutant receptor was much
      smaller than that of the wild type ones by several protein kinases. The other is
      up-regulation through activation of receptor gene expression. Protein kinase C
      (PKC) signaling was suggested to be involved in this up-regulation. Regulation of
      H1R expression level was mediated not only through H1R but also autonomic nerve
      receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down
      regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed
      not to be mediated by PKC activation, although PKC activation induced H1R
      phosphorylation. Elevation of H1R expression was induced by the stimulation of
      M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of
      beta2-adrenergic receptors induced H1R down-regulation through several
      mechanisms. One of them is enhanced receptor degradation after desensitization
      and another is suppression of receptor synthesis that includes the suppression of
      receptor gene expression and enhanced degradation of the receptor mRNA. Protein
      kinase A was suggested to be involved in enhanced degradation and the activation
      of the receptor gene expression. Elevation of both H1R expression and its mRNA
      was observed in nasal mucosa of nasal hypersensitivity allergy model rat after
      toluene diisocyanate provocation. These results suggest that activation of H1R
      gene expression plays an important patho-physiological role in allergy. Elevation
      of the mRNA was partially but significantly suppressed by antihistamines.

PMID- 16648671
TI  - [Early results of treatment with expandable intramedullary nails in femur shaft
      fractures].
AB  - OBJECTIVES: We evaluated the use of expandable intramedullary nails, their
      efficacy, and short-term results in the treatment of femur shaft fractures.
      METHODS: The study included 20 patients (10 females, 10 males; mean age 31 years;
      range 15 to 75 years) who were treated with expandable intramedullary nails
      (Fixion intramedullary femur nail) for femur shaft fractures. All the fractures
      were closed and were rated as type 32 A or B according to the AO classification.
      The mean duration from injury to surgery was three days (range 4 hours to 8
      days). The results were evaluated using the Thoresen criteria. The mean follow-up
      was 26 months (range 9 to 38 months). RESULTS: The mean operation time was 79
      minutes (range 45 to 120 min). Union was achieved in all the patients in a mean
      of 12.8 weeks (range 10 to 20 weeks). According to the Thoresen criteria, the
      results were excellent in 15 patients, good in one patient, fair in three
      patients, and poor in one patient. The results in all type A middle diaphyseal
      fractures were excellent. Of four patients with A2-3 distal metadiaphyseal
      fractures, one patient had a good result with a valgus of 5 degrees , and three
      patients had a fair result with a valgus ranging from 8 degrees to 10 degrees ,
      one of which also had 8-mm shortening. Delayed union, early or late infections,
      compartment syndrome, or bone necrosis were not seen. Of six patients who
      completed a follow-up of two years, the nails were removed in five patients,
      whereas removal was not possible in one patient due to a break in the upper part.
      CONCLUSION: Expandable intramedullary nails offer advantages in terms of ease of
      application and are less invasive than static nails and reamed applications.
      However, they may not provide adequate stability in metadiaphyseal regions and in
      fractures with fragments greater than 50%.

PMID- 16648672
TI  - [Evaluation of complications of femoral neck fractures in children operated on at
      least 24 hours after initial trauma].
AB  - OBJECTIVES: We evaluated complications and the factors affecting the development
      of avascular necrosis of the femoral head in children who underwent surgery for
      femoral neck fractures after at least a 24-hour delay. METHODS: We reviewed the
      results of 22 children (11 boys, 11 girls; mean age 10 years; range 4 to 14
      years) who were operated on after the first 24 hours for femoral neck fractures.
      According to the Delbet classification, two patients had type I, eleven patients
      had type II, and nine patients had type III fractures. Associated injuries were
      detected in seven patients. The mean duration from trauma to surgery was seven
      days (range 1 to 15 days). Internal fixation was performed following closed
      (n=20) or open (n=2) reduction. The results were assessed using the Ratliff
      criteria at the end of a mean follow-up of 73 months (range 18 to 184 months).
      The patients were evaluated with respect to age, type of fracture, displacement,
      complications, and avascular necrosis. RESULTS: The results were good in 12
      (54.6%), fair in eight (36.4%), and poor in two patients (9.1%). Complications
      developed in 17 patients (77.3%), 12 of whom had more than one. The most frequent
      complication was premature physeal closure (n=14; 63.6%) followed by avascular
      necrosis (n=12; 54.6%). No significant differences were found (i) with regard to
      age and the type of fracture between patients with and without avascular
      necrosis, and (ii) with regard to avascular necrosis between patients who were
      treated within the first and second week of trauma (p>0.05). CONCLUSION: The
      results of surgery performed after the first 24 hours are mainly influenced by
      the occurrence of avascular necrosis and, secondarily, by the type of fracture.

PMID- 16648673
TI  - [Can procalcitonin be used for the diagnosis and follow-up of postoperative
      complications after fracture surgery?].
AB  - OBJECTIVES: We investigated the effect of fracture surgery on serum procalcitonin
      levels and the value of procalcitonin in differentiating inflammatory reaction
      caused by fracture surgery from postoperative infective complications. METHODS:
      Twenty-one patients (8 women, 13 men; mean age 72.5 years; range 50 to 105 years)
      who underwent surgery for pertrochanteric hip fractures were evaluated according
      to the procedures employed, namely osteosynthesis, and hemiarthroplasty.
      Procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and
      body temperature were measured before surgery and for five days postoperatively.
      RESULTS: No postoperative wound infections occurred. Seven patients developed
      complications. The mean preoperative CRP level was five times above the normal.
      It made a peak on the second day and then began to decrease, but still was four
      times higher than the preoperative level on the fifth day. Preoperatively, the
      mean PCT level was lower than the normal in all the patients. It made a peak on
      the first postoperative day without exceeding the normal range and returned to
      the preoperative level on the fifth day. In contrast to CRP levels which were
      above the normal in all the patients, PCT levels were higher than the normal only
      in patients who developed complications. Taking the cut-off value as = or >0.5
      ng/ml, the sensitivity and specificity of PCT to determine systemic complications
      were 100% and 100% on the first day, and 100% and 50% on the second day,
      respectively. CONCLUSION: Procalcitonin may prove to be a useful parameter to
      identify early postoperative systemic complications after fracture surgery.

PMID- 16648674
TI  - [Approaches to distal humeral fractures in adults and comparison of treatment
      results].
AB  - OBJECTIVES: We compared the results of surgical techniques used in the treatment
      of distal humeral fractures. METHODS: The study included 22 patients (15 men, 7
      women; mean age 52 years; range 21 to 80 years) who were treated for closed
      distal humeral fractures. The fractures were classified according to the Muller's
      classification (18 type 3, 4 type 4) and Mehne-Matta's classification of
      intraarticular fractures. Following open reduction, internal fixation was
      performed with the use of double reconstructive plates in seven patients (32%),
      multiple K-wires in eight patients (36%), and multiple screws in seven patients
      (32%). The mean follow-up period was 42 months (range 24 to 72 months). The
      results were assessed using the Mayo Elbow Performance Scoring system. RESULTS:
      The results were very good in five patients (22.7%), good in eight patients
      (36.4%), fair in five patients, and poor in four patients (18.2%). Valgus and
      varus deformities were found in six (27.3%) and three (13.6%) patients,
      respectively, and 12 patients (54.6%) had decreased muscle strength. Two patients
      (9.1%) in the K-wire group developed instability due to insufficient union.
      Heterotopic ossification was detected in five patients (22.7%). None of the
      patients had persistent or severe pain. Two patients (9.1%) were free of pain,
      while 11 patients (50%) had occasional and mild pain, and nine patients (40.9%)
      had moderate pain on activity. The mean Mayo Elbow Performance scores were 88,
      72, and 55 with plate, screw, and K-wire applications, respectively. CONCLUSION:
      It was concluded that open reduction followed by internal fixation with double
      reconstructive plates was superior to K-wire and screw fixations in the treatment
      of distal humeral fractures.

PMID- 16648675
TI  - [The evaluation of patients undergoing total knee arthroplasty with or without
      patellar resurfacing].
AB  - OBJECTIVES: We evaluated the clinical and radiographic results of total knee
      arthroplasty (TKA) with or without patellar resurfacing. METHODS: The study
      included 149 knees of 126 patients who underwent TKA for primary knee
      osteoarthritis with (59 knees, group 1) or without (90 knees, group 2) patellar
      resurfacing. Clinical evaluations were made with the knee and function scores of
      the Knee Society, and patella scoring system; radiographic evaluations included
      changes in the joint line, Insall-Salvati ratio, lateral patellofemoral angle,
      and congruency angle. The mean follow-up period was 66.7 months (range 34 to 123
      months) in group 1, and 68.1 months (range 30 to 117 months) in group 2. RESULTS:
      Although postoperative knee and function scores showed significant improvements
      in both groups (p<0.001), these did not reach significance between the two groups
      (p>0.05). The mean patella scores did not differ significantly, either (p>0.05).
      Postoperative radiographic assessments did not show significant differences
      between the two groups with respect to mechanical axis values, patellar tilt, and
      lateral subluxation (p>0.05). Symptomatic patellar subluxation, dislocation,
      fracture or rupture of the extensor mechanism did not occur in any of the
      treatment groups. None of the patients required revision associated with the
      patella and patellar prosthesis. CONCLUSION: Our findings suggest that patellar
      resurfacing is not necessary other than patients with significant degeneration of
      the patellar surface.

PMID- 16648676
TI  - [Relationship between the mechanical and anatomic axis and orientation angles of
      the knee joint and functional capacity of patients with osteoarthritis].
AB  - OBJECTIVES: We investigated the relationship between the mechanical-anatomic axes
      and angles of the knee joint and functional levels of patients with primary
      osteoarthritis. METHODS: A total of 35 patients (27 females, 8 males; mean age
      58+/-9 years; range 42 to 77 years) with knee osteoarthritis were included. After
      physical examination, weight-bearing anteroposterior x-rays of the knees were
      obtained, on which measurements of the following were made: mechanical axis
      deviation (MAD), medial proximal tibial angle (MPTA), anatomic tibiofemoral angle
      (aTFA), mechanical lateral distal femoral angle (mLDFA), and joint line
      congruence angle (JLCA). Pain was evaluated by both the Western Ontario McMaster
      Osteoarthritis Index (WOMAC) and a visual analog scale (VAS). Functional capacity
      was assessed using the physical function and global indices of WOMAC. RESULTS:
      There was a moderate correlation between body mass index and the WOMAC global
      index (r=0.47, p<0.05). Radiographic evaluations revealed varus deformity in 28
      patients. There was a correlation between aTFA and the physical function (r=0.47)
      and global (r=0.41) indices of WOMAC (p<0.05). Functional capacity and pain were
      not correlated with the other mechanical angles of the knee joint (p>0.05).
      CONCLUSION: In view of our results, aTFA may be considered one important
      criterion in designing treatment and planning surgery for patients with primary
      osteoarthritis.

PMID- 16648677
TI  - [The relationship between phantom limb pain and neuroma].
AB  - OBJECTIVES: We evaluated the effect of exploratory neurectomy on phantom limb
      pain (PLP) in patients who had PLP and neuroma findings in the amputated
      extremity. METHODS: The study included 14 patients (13 males, 1 female; mean age
      30 years; range 21 to 54 years) who developed symptomatic neurinoma and PLP
      following amputation of an extremity due to trauma (9 mine blasts, 5 traffic
      accidents). Postamputation period ranged from 2.5 to 17 years (mean 5.5 years).
      All the patients had PLP of varying intensity and neuroma symptoms causing the
      sensation of a small electric shock, aroused by application of prosthesis,
      contact with bed, or on palpation. The mean visual analog scale (VAS) score for
      PLP was 8.4 (range 7 to 10) before neurectomy. The mean follow-up was 71.5 months
      (range 44 to 98 months). RESULTS: Complete recovery from PLP was achieved after
      neurectomy. Symptoms of neuroma completely disappeared during the follow-up
      period. Visual analog scale score was 0 in all the patients. CONCLUSION: The best
      way to prevent postamputation neuromas and PLP is to cut the nerve as proximal as
      possible, allowing its retraction into the soft tissue, and leaving its end away
      from the stump.

PMID- 16648678
TI  - [The results of arthroscopic repair in partial rotator cuff tears].
AB  - OBJECTIVES: We evaluated patients who underwent arthroscopic repair for partial
      rotator cuff tears less than 50% of tendon thickness with respect to the course
      of tears and functional results. METHODS: Nineteen patients (10 women, 9 men;
      mean age 49 years; range 40 to 70 years) who did not benefit from conservative
      treatment for partial rotator cuff tears were treated with arthroscopic
      debridement with or without subacromial decompression. Twelve patients had a
      history of trauma before the appearance of complaints which had a mean duration
      of 12 months (range 7 to 24 months) before arthroscopic repair. Partial tears
      were on the articular side in 12 patients, and on the bursal side in seven
      patients. The patients were assessed with preoperative and postoperative physical
      examination, magnetic resonance imaging (MRI), and UCLA scores. RESULTS: The mean
      preoperative and postoperative UCLA scores were 16.8 (range 10 to 20) and 29.0
      (range 9 to 35), respectively (p<0.05). The results were excellent or good in 14
      patients (73.7%), fair in two patients (10.5%), and poor in three patients
      (15.8%). One patient developed shoulder stiffness which improved following
      rehabilitation. Postoperative MRI showed persistence of partial tears in 13
      patients, progression in five patients, and development of total rupture in one
      patient. Complaints of pain increased in severity in patients in whom partial
      tears manifested a progressive course. One patient with total rupture underwent
      mini-open rotator cuff repair in the postoperative sixth month. CONCLUSION:
      Although clinical symptoms show improvement in most of the patients following
      arthroscopic treatment, partial rotator cuff tears do not heal completely in a
      considerable number of cases, and may progress to full-thickness tears in some.

PMID- 16648679
TI  - [Selection of treatment modalities in children with chronic osteomyelitis].
AB  - OBJECTIVES: We evaluated clinical and follow-up findings and treatment methods of
      pediatric patients with chronic osteomyelitis. METHODS: The study included 22
      children (14 boys, 8 girls; mean age 8+/-7 years) who were treated for chronic
      osteomyelitis. Infection sites were the femur, tibia, ulna, and radius in 11, 8,
      1, and 2 patients, respectively. Sixteen patients had a history of trauma.
      Fourteen patients had fractures, nine of which were associated with segmentary
      bone defects. All the patients underwent at least one debridement and received
      antibiotic treatment for at least six weeks. When necessary, medications were
      modified according to the antibiogram results. Cast immobilization was applied,
      but external fixation was used when bone instability existed. The mean follow-up
      period was 54 months. RESULTS: Clinical improvement was achieved in 13 patients
      following surgical debridement procedures, antibiotic treatment for six weeks,
      secondary grafting (5 patients), and cast immobilization. Of nine patients with
      segmentary bone losses, seven patients needed bone reconstruction procedures.
      Spontaneous shaft regeneration was observed in one patient with ulnar
      osteomyelitis. CONCLUSION: The results of surgical debridement and antibiotic
      treatment are satisfactory in more than half of the pediatric patients with
      chronic osteomyelitis. However, those developing segmentary bone defects after
      surgical debridement require bone reconstruction procedures.

PMID- 16648680
TI  - [The results of digital replantations at the level of the distal interphalangeal
      joint and the distal phalanx].
AB  - OBJECTIVES: We retrospectively evaluated replantations performed for distal
      amputations. METHODS: The study included 82 patients (75 males, 7 females; mean
      age 29 years; range 10 to 52 years) who underwent replantations distal to the
      distal interphalangeal joint for a total of 98 amputations. According to the
      Tamai classification, there were 58 zone 1 and 40 zone 2 amputations. Local
      digital anesthesia was used in 77 patients (93.9%). Arterial anastomosis was
      accomplished after bone fixation, and venous anastomosis and nerve repair were
      performed whenever possible. When venous anastomosis was not possible or in case
      of venous insufficiency, venous decompression was performed with heparinized
      gauze placed on the bleeding nail matrix. Functional results and the degree of
      patients' satisfaction with the cosmetic outcome were evaluated. The mean follow
      up was 16 months (range 3 to 46 months). RESULTS: Replantation was successful in
      60 amputations (61.2%) and unsuccessful in 38 cases (38.8%). In successful cases,
      cosmetic results were satisfactory due to the preservation of the nail and finger
      length. Functional results were satisfactory in cases in which the distal
      interphalangeal joint could be preserved. Replantations for zone 1 amputations
      (74.1%) yielded better results than those performed for zone 2 amputations
      (42.5%). CONCLUSION: Despite technical difficulties, replantations for distal
      finger amputations can provide satisfactory functional and cosmetic results.

PMID- 16648681
TI  - [Culturability of rat bone marrow stromal cells and evaluation for osteoblastic
      formation].
AB  - OBJECTIVES: We investigated culturability of bone marrow stromal cells of young
      mature rats and evaluated cultured cells with regard to histomorphologic features
      and osteoblastic formation. METHODS: Sixteen mature Wistar rats were sacrificed
      under high dose of ether anesthesia. Their femurs and tibias were removed,
      medullas and metaphyses were washed with carrier serum and the collected material
      was cultured in DME/F12 serum. The cells in the test medium and at the bottom of
      Petri dishes were studied under inverted microscope and were photographed. Then,
      the cells at the bottom were stained with the picro-thionin technique, examined
      under light microscope, and photographed. Following trypsinizing, cluster cells
      were dissolved and smears were prepared for histomorphologic evaluation of
      stromal cells. RESULTS: Rat bone marrow cells in the culture showed a high
      percentage of reproducibility (93.8%; 15/16). The stromal cells in Petri dishes
      were of different morphology, and were interspersed with large multinucleated
      osteoblast-like cells following staining with the picro-thionin technique.
      CONCLUSION: Our findings favor the opinion that cells harvested in bone marrow
      cell culture are very similar to osteoblastic cells and that they may stem from
      osteoprogenitor cells which have multifacet differentiation ability.

PMID- 16648682
TI  - [Comparison of the pull-out strengths of three different screws in pedicular
      screw revisions: a biomechanical study].
AB  - OBJECTIVES: We investigated the possible effects of three pedicular screws on
      axial pull-out strength in pedicular revision surgery. METHODS: Two study groups
      were formed from calf lumbar vertebrae. Initially, Alici pedicular screws with an
      outer diameter of 6.5 mm were applied (with or without tapping) to all the
      pedicles. All the pedicles were subjected to axial pull-out testing to induce
      pedicular insufficiency. Then, Alici pedicular screws with an outer diameter of 7
      mm were applied to the left pedicles. The right pedicles in the two study groups
      were assigned to receive two different types of pedicular screws with an
      expandable (enlargeable) end, respectively. Axial pull-out testing was repeated
      in both groups and the results were compared with the initial pull-out strength
      values. RESULTS: In the first group, 65% and 64% of the initial pull-out
      strengths were obtained with 7-mm Alici pedicular screws and with expandable
      pedicular screws, for the left and right pedicles, respectively. The
      corresponding pull-out strengths in the other study group were 70% and 68.5% of
      the initial values, respectively. Tapping of the screw hole entrance resulted in
      a mean decrease of 13% in the pull-out strength compared to screw applications
      without tapping. CONCLUSION: Pedicular screw revisions using a 0.5 mm greater
      screw in diameter did not provide adequate screw-bone inter-face strength and
      pedicle filling. Similarly, expandable pedicular screws did not contribute to
      screw stability.

PMID- 16648683
TI  - [A case of isolated tuberculous tenosynovitis of the flexor tendon of the third
      finger of the hand].
AB  - A 55-year-old female patient presented with a painless swelling in the palm of
      the right hand, causing restriction of the third finger. Magnetic resonance
      imaging revealed a synovial lesion in the flexor tendon sheath of the third
      finger, showing heterogenous contrast. Open biopsy and histopathological studies
      showed a granulomatous infectious reaction of the synovial tissue. A diagnosis of
      tuberculosis was made, after which antituberculosis treatment was instituted.
      Total regression was achieved after nine months of medical treatment without
      further extensive surgical measures. At the end of nine months, the movements of
      the finger were found to be normal and painless.

PMID- 16648684
TI  - [Symptomatic lumbar intraspinal synovial cyst: a case report].
AB  - Synovial and ganglion cysts, also known as juxta-facet cysts, are intraspinal
      lesions that may mimic disc herniations and cause radicular symptoms. A 75-year
      old male patient presented with a 6-month history of left leg pain and numbness
      in the foot that increased in severity within the past week. Physical examination
      showed motor deficit of the left extensor hallucis longus muscle (4/5) and
      hypoesthesia on the left L4-5 dermatomes. Magnetic resonance imaging revealed an
      intraspinal cyst originating from the L4-5 facet joint. Medial facetectomy and
      cyst excision were performed, which provided immediate relief of pain. He had no
      loss of strength of the extensor hallucis longus muscle and his neurologic
      examination was normal during the first postoperative year.

PMID- 16648685
TI  - [Surgical treatment of hand deformities in multiple enchondromatosis: a case
      report].
AB  - Multiple enchondromatosis (Ollier's disease) is a rare disease characterized by
      widespread enchondromas. In general, the short tubular bones of the hand are
      involved, with progressive lesions resulting in cosmetic problems and functional
      deformities. Diaphysectomy and reconstruction with structural autografts or
      allografts are usually recommended in the treatment of extensive enchondromas
      involving the fingers. Curettage and grafting and ray amputation are other
      surgical procedures that can be applied depending on the severity of involvement.
      A 25-year-old woman with enchondromatosis presented with severe swelling and
      deformities on her fingers in both hands. The majority of the lesions were
      managed by diaphysectomy and reconstruction with structural grafts; ray
      amputation, curettage and grafting were performed for more severe lesions. During
      a long-term follow-up (left hand 6 years, right hand 5.5 years) cosmetic and
      functional results were acceptable.

PMID- 16648686
TI  - [Contribution of biomechanics to anterior cruciate ligament reconstruction].
AB  - For years, bioengineers and orthopedic surgeons have applied the principles of
      biomechanics to gain valuable information about the complex function of the
      anterior cruciate ligament (ACL), as well as to improve the design of replacement
      grafts for ACL reconstruction. New experimental tools, such as robotic testing
      systems and mathematical models have been used to measure the multiple degree-of
      freedom (DOF) knee kinematics, in situ forces, and biomechanical properties of
      the ACL. This manuscript will review specific examples of how biomechanics has
      impacted surgical reconstruction of the ACL by improving technical factors such
      as graft selection, tunnel placement, initial graft tension, graft fixation, and
      graft tunnel healing. Evolution of the single-bundle ACL reconstruction to the
      more anatomical double-bundle reconstruction will be featured. Finally, the
      future role of biomechanics to facilitate in vivo data for further improvement of
      ACL reconstruction will be discussed.

PMID- 16648687
TI  - Safety nets, savings, and bracing to face it all.

PMID- 16648688
TI  - An analysis of the ethical and linguistic content of hospital mission statements.
AB  - An analysis of the ethical and functional linguistic content of Canadian hospital
      mission statements was conducted. The ethical content analysis identified
      deontology as the dominant ethical orientation. The functional linguistic
      analysis revealed a trend toward the depersonalization and objectification of
      action. Implications for formulating effective mission statements were discussed.

PMID- 16648689
TI  - Hospital service offerings: does Catholic ownership matter?
AB  - Controlling for market and organizational characteristics, Catholic hospitals in
      2001 offered more stigmatized and compassionate care services than investor-owned
      hospitals, and more stigmatized services than public hospitals. There were no
      differences between Catholic hospitals and other nonprofit hospitals, however, in
      the number of compassionate, stigmatized, and access services offered. This may
      reflect growing isomorphism in the nonprofit hospital sector.

PMID- 16648690
TI  - Are consumers reshaping hospitals? Complementary and alternative medicine in U.S.
      Hospitals, 1999-2003.
AB  - All types of acute care hospitals across the U.S. are becoming increasingly
      involved in offering CAM services. Hospitals appear to be responding to consumer
      demand, CAM specific market forces, and their organizational missions but not to
      regulatory mandates.

PMID- 16648691
TI  - An integrative health information systems approach for facilitating strategic
      planning in hospitals.
AB  - This article presents a framework for developing strategic information systems
      (SISs) for hospitals. It proposes a SIS formulation process which incorporates
      complexity theory, strategic/organizational analysis theory, and conventional MIS
      development concepts. Within the formulation process, four dimensions of SIS are
      proposed as well as an implementation plan. A major contribution of this article
      is the development of a hospital SIS framework which permits an organization to
      fluidly respond to external, interorganizational, and intraorganizational
      influences. In addition, this article offers a checklist which managers can
      utilize in developing an SIS in health care.

PMID- 16648692
TI  - SMS reminders in the UK national health service: an evaluation of its impact on
      "no-shows" at hospital out-patient clinics.
AB  - The ownership of cell phones and use of short message service (SMS) are
      sufficiently common in the United Kingdom to be exploited by health services
      providers. The study evaluates their use to reduce nonattendance at out-patient
      clinics. The impact is modest, but so also is the cost, about 7.50 pounds (13.13
      dollars, 10.88 euros) per "no-show" avoided.

PMID- 16648693
TI  - An exploration of job design in long-term care facilities and its effect on
      nursing employee satisfaction.
AB  - This study used quantitative and qualitative methods to examine the design of
      nursing jobs in long-term care facilities and the effect of job design on
      employee satisfaction.

PMID- 16648694
TI  - Financial consequences of rural hospital long-term care strategies.
AB  - Data for 540 rural hospitals from 1982 to 1997 were analyzed to determine whether
      adoption of long-term-care (LTC) strategies improved hospital financial
      performance. Adoption of external and internal LTC strategies (other than swing
      beds) was generally, but not unambiguously, associated with higher profits,
      increased occupancy, and/or lower costs.

PMID- 16648695
TI  - Organizational commitment and turnover of nursing home administrators.
AB  - In this investigation, the associations between organizational commitment (OC),
      intent-to-turnover, and actual turnover of a large sample of nursing home
      administrators (NHAs) are examined. Data used come from a mail survey, from which
      632 responses were received from the NHAs (response rate = 63%). The one-year
      turnover rate of NHAs was 39 percent, and in almost all cases (87%) these NHAs
      had also exhibited low OC scores. The intent-to-turnover results show thinking
      about quitting comes before searching for a new position, which in turn both
      comes before the intention to quit. Multivariate analyses show work overload has
      a strong and robust association with both intent-to-turnover and turnover of
      NHAs, and may indicate that NHAs are leaving their positions because they are
      understaffed.

PMID- 16648696
TI  - Selective screw placement in forearm compression plating: results of 75
      consecutive fractures stabilized with 4 cortices of screw fixation on either side
      of the fracture.
AB  - OBJECTIVES: To (1) assess the effectiveness of an alternative plate and screw
      construct for all diaphyseal forearm fracture patterns and (2) test the
      hypothesis that as the working length (WL) to plate length (PL) ratio increases,
      so does the construct instability and therefore likelihood of failure. DESIGN:
      Retrospective. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Sixty-three
      patients were operatively treated and 53 were available for follow-up, totaling
      75 diaphyseal fractures (19 ulna, 12 radius, and 22 radius/ulna). Average follow
      up was 14.6 months (8-26). MAIN OUTCOME MEASUREMENTS: Patients were followed
      postoperatively at 1 to 2 weeks, 6 weeks, 10 weeks, 4 months, and then at 3 month
      intervals. Radiographs were analyzed for changes in fracture alignment, loose or
      broken hardware, and fracture-healing characteristics. Fracture union was defined
      when a fracture was radiographically healed and clinically asymptomatic, and the
      patient was able to return to all activities without restrictions. RESULTS: No
      fractures showed radiographic evidence of changes in alignment after fixation.
      There were no refractures, no infections, and one nonunion. The overall union
      rate after the index procedure was 97.1% for the radius and 97.6% for the ulna.
      WL:PL ratio averaged 0.17 (range 0-0.57) and the most frequently used PL was 7
      holes (n=43). Patients with closed fractures did have a significantly reduced
      time to union when compared to those with open fractures (P=0.002). Overall union
      rate averaged 9.8 weeks (range 6-32 weeks). CONCLUSIONS: Fixation with a standard
      length compression plate and four cortices of screw fixation on either side of
      the fracture seems to be a stable construct for diaphyseal forearm fractures and
      may result in union rates equivalent to those cited in the literature.

PMID- 16648697
TI  - The olecranon osteotomy: a six-year experience in the treatment of intraarticular
      fractures of the distal humerus.
AB  - OBJECTIVES: The transolecranon exposure for distal humerus fractures is a
      suggested technique for improving articular visualization, allowing accurate
      reduction. Significant osteotomy complications such as nonunion and implant
      prominence have prompted recommendations for alternate exposures. The purposes of
      this study are to present the techniques and complications of the olecranon
      osteotomy for the management of distal humerus fractures, and to evaluate the
      adequacy of distal humeral and olecranon articular reductions. DESIGN:
      Retrospective review. SETTING: Urban level-1 University trauma center. PATIENTS:
      One hundred fourteen skeletally mature AO/OTA type 13-C distal humerus fractures
      were identified from the orthopedic trauma database and formed the study group.
      INTERVENTION: Seventy fractures (61%), including 42 open injuries, were managed
      using an intraarticular, chevron-shaped olecranon osteotomy. Osteotomy fixations
      were performed with an intramedullary screw and supplemental dorsal ulnar wiring,
      or plate stabilization. In the remaining 44 fractures (39%), soft-tissue
      mobilizing exposures were performed. MAIN OUTCOME MEASURE: Patient records and
      radiographs were reviewed to determine injury and operative characteristics,
      complications, and adequacy of articular reductions. Patient interviews were
      conducted by telephone to identify any subsequent surgical procedures. RESULTS:
      The proportion of osteotomies performed increased as fracture complexity
      increased (P<0.001). Sixty-seven of 70 patients had adequate follow-up to
      determine osteotomy union. All osteotomies united. There was 1 delayed union.
      Sixty-one of 70 patients had adequate follow-up to determine complications
      associated with ulnar fixations. Five of these patients (8%) underwent elective
      removal of symptomatic osteotomy fixations. An additional 13 patients had
      olecranon implants removed in conjunction with other surgical procedures (11
      elbow contracture releases, 1 humeral nonunion repair, and 1 chronic draining
      sinus excision). Symptomatic ulnar fixations in this group could not be reliably
      ascertained, but may have been present. A total of 18 of 61 patients (29.5%),
      therefore, had proximal ulna fixations removed. All patients treated using an
      olecranon osteotomy exposure demonstrated satisfactory radiographic distal
      humeral articular reductions. Two osteotomies required early revision
      osteosynthesis secondary to loss of osteotomy reduction. CONCLUSIONS: In this
      study, no osteotomy nonunions were encountered in 67 patients, more than half of
      which were open injuries. Regardless of which type of fixation is used to secure
      the osteotomy, secure stabilization must be obtained. Isolated symptomatic
      olecranon fixation requiring removal occurred in approximately 8% of patients.
      Although not necessary for all fractures of the distal humerus, the olecranon
      osteotomy can be useful in the visualization of the complex articular injuries,
      allowing accurate articular reduction.

PMID- 16648698
TI  - Outcomes for older patients with hip fractures: the impact of orthopedic and
      geriatric medicine cocare.
AB  - OBJECTIVES: To assess the impact of a specifically designed model of orthopedic
      geriatric cocare on hip fracture (HF) outcomes. SETTING: Tertiary teaching
      hospital (level I trauma center). DESIGN: Prospective observational study with a
      retrospective (historical) control. Data on 951 consecutive patients 60 years of
      age or older admitted to the authors' institution with a nonpathologic HF over a
      7-year period (1995 to 2002) were analyzed. Between 1995 and 1997, medical
      problems were managed by a geriatric medicine (GM) consultation-only service
      (retrospective audit). In 1998, a GM registrar began overseeing daily medical
      care with weekly geriatrician consultant review (prospective study). Outcomes for
      2 time periods were compared: a 3-year period before (no GM; 504 patients) and a
      4-year period after (GM; 447 patients) the introduction of GM cocare. MAIN
      OUTCOME MEASUREMENTS: Postoperative medical complications, mortality, length of
      stay, discharge destination, use of thromboprophylaxis, and antiosteoporotic
      treatment. RESULTS: While comparing 2 periods (GM and no GM), significant
      reductions in postoperative medical complications and comorbid conditions (in
      total 49.5% vs. 71.0%, P<0.001) and mortality (4.7% vs. 7.7%, P<0.01) occurred
      and rehospitalization to medical wards within 6 months decreased (28% vs. 7.6%).
      However, no differences were observed in median length of hospital stay (10.8 vs.
      11.0 days) or in discharge destination. Antiosteoporotic treatment (12% to 69%)
      and specific thromboprophylaxis (63% to 94%) increased in the GM period.
      CONCLUSIONS: Orthopedic-geriatric cocare for the older patients with HF was
      associated with significant reductions in morbidity and mortality, and increases
      in optimal postoperative care. Options for further improvement of orthopedic-GM
      cocare need to be investigated.

PMID- 16648699
TI  - The risk of local infective complications after damage control procedures for
      femoral shaft fracture.
AB  - OBJECTIVES: To determine infection rates after damage control orthopaedics (DCO)
      and primary intramedullary nailing (1' IMN) in multiply injured patients with
      femoral shaft fracture. DESIGN: Retrospective case analysis. SETTING: Level I
      trauma center. PATIENTS: All patients with New Injury Severity Score (NISS) >20
      and femoral shaft fracture (AO 32-) treated in our unit between 1996 and 2002.
      INTERVENTION: Damage control orthopaedics, defined as primary external fixation
      of the femoral shaft fracture and subsequent conversion to an intramedullary
      nail, or primary IMN. MAIN OUTCOME MEASUREMENTS: Rates of infection classified as
      contamination (positive swabs with no clinical change), superficial, deep
      (requiring surgery), and removal of hardware (those requiring removal of femoral
      instrumentation or amputation). RESULTS: A total of 173 patients with 192
      fractures were included; 111 fractures were treated by DCO and 81 by primary IMN.
      Mean follow-up was 19.1 months [median, 16.7, range, 1 (patient died)-67 months].
      DCO patients had a significantly higher NISS and more grade III open fractures
      (P<0.001). IMN procedures took a median of 150 minutes compared with 85 minutes
      for DCO (P<0.0001). Although wound contamination (including contaminated pin
      sites) was more common in the DCO group (P<0.05), the risk of infectious
      complications was equivalent (P=0.86). Contamination was significantly more
      likely when conversion to IMN occurred after more than 14 days (P<0.05); however,
      this did not lead to more clinically relevant infections. Logistic regression
      analysis showed that although a DCO approach was not associated with infection,
      delay before conversion in the DCO group might be [P=0.002 for contamination and
      removal of hardware, P=0.065 for serious infection (deep or worse), not
      significant for other infection outcomes]. Grade III open injury also was
      significantly associated with serious infection in all patients (P<0.05).
      CONCLUSIONS: Infection rates after DCO for femoral fractures are comparable to
      those after primary IMN. We see no contraindication to the implementation of a
      damage control approach for severely injured patients with femoral shaft fracture
      where appropriate. Pin-site contamination was more common where the fixator was
      in place for more than 2 weeks. For patients treated by using a DCO approach,
      conversion to definitive fixation should be performed in a timely fashion.

PMID- 16648700
TI  - Locked plates combined with minimally invasive insertion technique for the
      treatment of periprosthetic supracondylar femur fractures above a total knee
      arthroplasty.
AB  - OBJECTIVE: New locked plate devices offer theoretical advantages for the
      treatment of supracondylar femur fractures associated with a total knee
      arthroplasty (TKA). These devices also can be inserted with relative ease by
      using minimally invasive techniques, provide a fixed angle construct, and improve
      fixation in osteoporotic bone. The purpose of this study was to evaluate the
      results and complications of treating periprosthetic supracondylar femur
      fractures above a TKA with a locked plate designed for the distal femur. DESIGN:
      Prospective, consecutive case series. SETTING: Level I trauma center.
      PATIENTS/PARTICIPANTS: Twenty-two consecutive adult patients with 24 (2
      bilateral) supracondylar femur fractures (OTA 33A) above a well-fixed non-stemmed
      TKA were treated with the Locking Condylar Plate. One patient who died before
      fracture healing and 1 who was lost to follow-up were excluded from analysis. All
      remaining patients (5 males, 15 females, average age, 73 (range, 50-95) years)
      were available for follow-up at an average of 15 (range, 6-45) months. According
      to the OTA classification, there were three 33A1, eight 33A2, and eleven 33A3
      fractures. All fractures were closed. Indirect reduction methods without bone
      graft were used in all cases. RESULTS: Nineteen of 22 fractures healed after the
      index procedure (86%). All 3 patients with healing complications were insulin
      dependent patients with diabetes who also were obese (body mass index >30). Two
      developed infected nonunions and 1 an aseptic nonunion. Postoperative alignment
      was satisfactory (within 5 degrees ) for 20 of 22 fractures. Fracture of screws
      in the proximal fragment occurred in 4 patients. In 3 of these cases, there was
      progressive coronal plane deformity. There was no change in alignment in any
      other patient. Fifteen of 17 patients who healed returned to their baseline
      ambulatory status, with 5 requiring additional ambulatory support compared with
      baseline. CONCLUSIONS: Fixation of periprosthetic supracondylar femur fractures
      with a locking plate provided satisfactory results in nondiabetic patients.
      Diabetic patients seem to be at high risk for healing complications and
      infection.

PMID- 16648701
TI  - Simultaneous treatment of tibial bone and soft-tissue defects with the Ilizarov
      method.
AB  - OBJECTIVES: To evaluate the potential for limb salvage using the Ilizarov method
      to simultaneously treat bone and soft-tissue defects of the leg without flap
      coverage. DESIGN: Retrospective study. SETTING: Level I trauma centers at 4
      academic university medical centers. PATIENTS/PARTICIPANTS: Twenty-five patients
      with bone and soft-tissue defects associated with tibial fractures and nonunions.
      The average soft-tissue and bone defect after debridement was 10.1 (range, 2-25)
      cm and 6 (range, 2-14) cm respectively. Patients were not candidates for flap
      coverage and the treatment was a preamputation limb salvage undertaking in all
      cases. INTERVENTION: Ilizarov and Taylor Spatial Frames used to gradually close
      the bone and soft-tissue defects simultaneously by using monofocal shortening or
      bifocal or trifocal bone transport. MAIN OUTCOME MEASUREMENTS: Bone union, soft
      tissue closure, resolution or prevention of infection, restoration of leg length
      equality, alignment, limb salvage. RESULTS: The average time of compression and
      distraction was 19.7 (range, 5-70) weeks, and time to soft-tissue closure was
      14.7 (range, 3-41) weeks. Bony union occurred in 24 patients (96%). The average
      time in the frame was 43.2 (range, 10-82) weeks. Lengthening at another site was
      performed in 15 patients. The average amount of bone lengthening was 5.6 (range,
      2-11) cm. Final leg length discrepancy (LLD) averaged 1.2 (range, 0-5) cm. Use of
      the trifocal approach resulted in less time in the frame for treatment of large
      bone and soft-tissue defects. There were no recurrences of osteomyelitis at the
      nonunion site. All wounds were closed. There were no amputations. All limbs were
      salvaged. CONCLUSIONS: The Ilizarov method can be successfully used to
      reconstruct the leg with tibial bone loss and an accompanying soft-tissue defect.
      This limb salvage method can be used in patients who are not believed to be
      candidates for flap coverage. One also may consider using this technique to avoid
      the need for a flap. Gradual closure of the defect is accomplished resulting in
      bony union and soft-tissue closure. Lengthening can be performed at another site.
      A trifocal approach should be considered for large defects (>6 cm). Advances in
      technique and frame design should help prevent residual deformity.

PMID- 16648702
TI  - Reduction plating for provisional fracture fixation.
AB  - Obtaining and maintaining the reduction of high-energy, complex fractures
      involving the periarticular or shaft regions of the bone often is difficult with
      standard reduction clamps. We present and review a technique in which unicortical
      fracture fixation plates are applied at provisional states of reduction to
      maintain that reduction until definitive fixation can be applied. We have termed
      the technique "reduction plating," and modifications of this concept have proven
      useful in metadiaphyseal and diaphyseal fractures, periarticular fractures and
      acetabular fractures. This overarching concept and its modifications are
      described.

PMID- 16648703
TI  - Arthroscopically-assisted removal of retrograde intramedullary femoral nails.
AB  - Retrograde nailing of femoral shaft fractures has become more prevalent as a
      result of its growing acceptance and familiarity to orthopaedic surgeons. Nail
      removal is occasionally indicated, which may require a formal arthrotomy. We
      describe an arthroscopic removal technique that has several advantages. The
      percutaneous technique imparts less morbidity than a more extensive arthrotomy.
      More importantly, additional intra-articular pathology can be thoroughly assessed
      and treated, such as meniscal tears and chondral injury, which may have occurred
      at the time of injury. These are potential causes of knee pain, which usually
      cannot be properly diagnosed without arthroscopy. Our findings also support the
      existence of a stable fibrous cap, which forms over the entry portal of a well
      seated retrograde femoral nail as well as no evidence of intra-articular
      metallosis.

PMID- 16648704
TI  - Simultaneous ipsilateral posterior knee and hip dislocations: case report,
      including a technique for closed reduction of the hip.
AB  - In isolation, dislocations of the hip and knee require emergent reduction to
      minimize the risks of serious complications, including vascular and neurologic
      injury, osteonecrosis of the femoral head, and loss of motion and function. With
      simultaneous dislocation of the ipsilateral hip and knee, as in the situation of
      hip dislocation with concomitant femoral shaft fracture, reduction of the hip may
      prove difficult because of the inability to control the femoral segment. In this
      setting, general anesthesia is commonly required. We present the case of a
      patient who sustained an ipsilateral hip and knee dislocation who underwent
      closed reduction of the knee in the emergency department but required general
      anesthesia and the insertion of Schanz pins in the femur to reduce the hip
      dislocation.

PMID- 16648705
TI  - Traumatic inferior hip dislocation in an adult with ipsilateral trochanteric
      fracture.
AB  - Traumatic Inferior dislocation of hip in adult is an extremely rare occurrence.
      We report a case of an inferior hip dislocation associated with an
      intertrochanteric fracture. Treatment consisted of an initial closed manipulative
      reduction of the dislocation with the aid of a Schanz screw inserted in a T
      handle universal chuck and using C-arm imaging. A dynamic hip screw was then used
      to fix the intertrochanteric fracture. At 2.5 years after the injury, the patient
      has symmetrical range of motion versus his contra lateral normal hip. Radiographs
      of the hip show normal anatomy without signs of avascular necrosis of the femoral
      head. To our knowledge, this is the first reported case of an adult with an
      inferior hip dislocation with a trochanteric fracture.

PMID- 16648706
TI  - Primary talectomy after open total dislocation of the talus: a case report with
      13 years follow-up.
AB  - Total dislocation of the talus is a rare and severe injury. We report a case of
      an open total anterolateral dislocation of the left talus with simultaneous
      contralateral open peritalar dislocation. The former injury was managed with a
      primary talectomy because of severe contamination and blood supply deprivation.
      Thirteen years later, the patient complains of mild symptoms on the talectomy
      side. In contrast, the patient has more serious clinical problems (panarthritis)
      on the side of the peritalar dislocation.

PMID- 16648707
TI  - Scapula fractures: to fix or not to fix?

PMID- 16648708
TI  - Treatment of scapula fractures: systematic review of 520 fractures in 22 case
      series.
AB  - BACKGROUND: Fractures of the scapula account for 3% to 5% of all fractures of the
      shoulder girdle and make up less than 1% of all broken bones. Scapula fractures
      typically occur after high-energy trauma, and approximately 90% of the patients
      have associated injuries. OBJECTIVE: (1) To determine the incidences of
      nonoperative and operative treatment of different scapula fracture types, (2) to
      systematically stratify the reported results of nonoperatively and operatively
      treated scapula fractures on the basis of different fracture types and to
      summarize functional results, and (3) to quantify infection and secondary
      surgical procedure rates after operative treatment.

PMID- 16648709
TI  - Low incidence of ulnar nerve injury with crossed pin placement for pediatric
      supracondylar humerus fractures using a mini-open technique.

PMID- 16648721
TI  - A systems approach in nursing administration: structure, process, and outcome.
AB  - This article presents a systems approach for administrators to consider as they
      review structure, process, and outcome in their healthcare organization. Systems
      provide a way to access data, information, and knowledge. Systems organize and
      unify the complex world of nursing practice in healthcare systems. Use of King's
      conceptual system, Theory of Goal Attainment, and transaction process is
      presented as an example that helps the multiple individuals and groups use
      information and knowledge to structure nursing practice. The transaction process
      helps individuals and groups identify goals and outcomes that lead to effective
      nursing care, evidence-based practice, and cost-effectiveness.

PMID- 16648722
TI  - Partners in caring: a partnership for healing.
AB  - This article describes one organization's effort to create a family-friendly
      environment that supports the choice of patients for involvement of a family
      member or loved one in their care. Changing a culture requires a process that can
      emotionally drive the caregivers to agree with the need to change and sustain the
      efforts over a long period. This project, Partners in Caring, describes the
      philosophy, the journey of changing a culture, and the results achieved over a 7
      year period. The Partners in Caring philosophy is "a commitment between a
      patient, care partner and healthcare team to a relationship of hands-on support
      based on compassion, communication and choice empowering people to heal in a
      nurturing manner." This concept laid a foundation for the development of a new
      model of care, which is described. The implementation has resulted in an improved
      patient and staff satisfaction and a decrease in patient complaints.

PMID- 16648723
TI  - Nurse shift report: who says you can't talk in front of the patient?
AB  - Bedside nurse shift report is a process where nurses provide shift-to-shift
      report at the patient's bedside so the patient can be more involved in his or her
      care. There are many benefits of bedside report, including relationship building
      between staff members and increased patient satisfaction, to both the patient and
      to the healthcare team. Concerns about the traditional methods of communication
      between the various shifts helped drive a nursing unit's decision to move to a
      more patient-involved model of shift-to-shift report. The change from the
      traditional taped report between healthcare providers to bedside reporting
      focused on patients wanting more involvement in their care, activities, and
      current status. Patients also wanted updates about their health status, their
      medical plan as well as information about their progress toward their goals.
      This, coupled with Banner Desert Medical Center's Care Model, embraces patient
      centered care, King's Theory of Goal Attainment, and keeps the patient informed.
      The current nursing shift report did not meet the medical center's model of care
      on any of these aspects. This article will include information on the benefits of
      bedside nurse shift-to-shift report, how one unit implemented bedside reporting,
      and some of the outcomes achieved after implementing this change at a 600-bed
      urban medical center.

PMID- 16648724
TI  - Consumer preferences and values as an integral key to evidence-based practice.
AB  - Although evidence-based practice (EBP) integrates the best evidence from well
      designed studies with a clinician's expertise and patient preferences and values,
      most of what is emphasized in books and reports on EBP is the 5-step EBP process.
      However, the consideration of patient values and preferences in making clinical
      decisions is essential to deliver the highest quality of care. This article
      briefly reviews the status of EBP in the United States, described the ARCC
      mentorship model, and highlights how to engage consumers in the EBP process.

PMID- 16648725
TI  - Customer-driven outcomes: a patient and family perspective.
AB  - Experiencing the healthcare system during an acute surgical event highlighted
      factors that contributed to customer-driven outcomes. Communicating intentions of
      and rationale for interventions increased the patient and family's confidence,
      and engaged the whole mind-body connection into the healing process. Utilizing
      the family as a repository of patient information incorporated their perspective,
      knowledge, and wisdom into the delivery and evaluation of patient care. Lastly,
      fostering the relationship between the nurse and the patient and family
      strengthened the therapeutic process, thus providing a foundation for customizing
      care.

PMID- 16648726
TI  - Fifty? Prepare for the battle for your life.

PMID- 16648727
TI  - Veterans Health Administration Office of Nursing Services exploration of positive
      patient care synergies fueled by consumer demand: care coordination, advanced
      clinic access, and patient self-management.
AB  - The consumers who utilize the Veterans Health Administration healthcare system
      are older, and most are learning to live with chronic diseases. Their desires and
      needs have driven changes within the Veterans Health Administration. Through
      patient satisfaction initiatives and other feedback sources, consumers have made
      it clear that they do not want to wait for their care, they want a say in what
      care is provided to them, and they want to remain as independent as possible. Two
      interdisciplinary processes/models of healthcare are being implemented on the
      national level to address these issues: advanced clinic access and care
      coordination. These programs have a synergistic relationship and are integrated
      with patient self-management initiatives. Positive outcomes of these programs
      also meet the needs of our staff. As these new processes and programs are
      implemented nationwide, skills of both patients and nursing staff who provide
      their care need to be enhanced to meet the challenges of providing nursing care
      now and into the 21st century. Veterans Health Administration Office of Nursing
      Services Strategic Planning Work Group is defining and implementing
      processes/programs to ensure nurses have the knowledge, information, and skills
      to meet these patient care demands at all levels within the organization.

PMID- 16648728
TI  - Parents influence and advance pediatric policy.
AB  - Consumers are driving outcomes in healthcare. In children's hospitals, the
      consumers are the parents and the patients. This article describes the process
      undertaken to respond to parents' requests to be present during the induction of
      anesthesia in their child. The process of changing long-standing practices in a
      complex organization undergoing major change in becoming a children's hospital is
      described in detail.

PMID- 16648729
TI  - Physician hospital consumer collaboration.
AB  - The authors describe a disease management initiative designed to address issues
      of noncompliance in a diabetic population. The program design was a collaborative
      effort between a payer and a public health organization representing Hartford
      Hospital and Hartford Physicians Association. Interventions included a patient
      self-assessment, phone counseling, and a monetary reward for program
      participation.

PMID- 16648730
TI  - The clinical nurse leader: promoting patient-centered outcomes.
AB  - In 2004, a 551-bed nonprofit hospital launched a pilot of the unit-based clinical
      nurse leader (CNL) role to support staff nurses and their patients. Thus far, the
      role has demonstrated great promise in promoting individual patient-centered
      outcomes, although the pilot has identified potential adaptations to enhance
      aggregate outcomes. These include decreasing the patient-to-CNL ratio, increasing
      CNL availability to 7 days a week, and reconsidering whether to fill CNL
      positions with nurses who were prepared as nurse practitioners.

PMID- 16648731
TI  - Use of NCLEX preparation strategies in a hospital orientation program for
      graduate nurses.
AB  - This article describes outcomes from the first year of a hospital orientation
      program for graduate nurses that was expanded to systematize and enrich
      preparation of graduate nurses for success on the NCLEX-RN licensure examination.
      The study protocol provided the Assessment Technologies Institute predictor
      examination to assess risk for licensure examination failure, review materials,
      and a meeting with an education specialist to identify and prioritize study
      needs. Those at highest risk for failure were also provided an in-depth written
      study plan and ongoing follow-up and support until the licensure examination was
      taken. The study sample consisted of 90 graduate nurses who were hired from May
      through August of 2005 at the University of Kansas Hospital. The pass rate for
      participants was 86.7% on the first attempt in year 1 of the program. At-risk
      graduates who reported that the predictor results impacted their study habits and
      followed the study recommendations were more likely to pass the licensure
      examination. Graduate nurses reported a high level of satisfaction with the
      support provided. Specific challenges faced by hospital nurse administrators in
      recruitment and retention and return on investment over a 3-year improvement plan
      are described.

PMID- 16648732
TI  - Stability of dynamic trunk movement.
AB  - STUDY DESIGN: Nonlinear systems analyses of trunk kinematics were performed to
      estimate control of dynamic stability during repetitive flexion and extension
      movements. OBJECTIVE: Determine whether movement pace and movement direction of
      dynamic trunk flexion and extension influence control of local dynamic stability.
      SUMMARY OF BACKGROUND DATA: Spinal stability has been previously characterized in
      static, but not in dynamic movements. Biomechanical models make inferences about
      static spinal stability, but existing analyses provide limited insight into
      stability of dynamic movement. Stability during dynamic movements can be
      estimated from Lyapunov analyses of empirical data. METHODS: There were 20
      healthy subjects who performed repetitive trunk flexion and extension movements
      at 20 and 40 cycles per minute. Maximum Lyapunov exponents describing the
      expansion of the kinematic state-space were calculated from the measured trunk
      kinematics to estimate stability of the dynamic system. RESULTS: The complexity
      of torso movement dynamics required at least 5 embedded dimensions, which
      suggests that stability components of lumbar lordosis may be empirically
      measurable in addition to global stability of trunk dynamics. Repeated
      trajectories from fast paced movements diverged more quickly than slower
      movement, indicating that local dynamic stability is limited in fast movements.
      Movements in the midsagittal plane showed higher multidimensional kinematic
      divergence than asymmetric movements. CONCLUSION: Nonlinear dynamic systems
      analyses were successfully applied to empirically measured data, which were used
      to characterize the neuromuscular control of stability during repetitive dynamic
      trunk movements. Movement pace and movement direction influenced the control of
      spinal stability. These stability assessment techniques are recommended for
      improved workplace design and the clinical assessment of spinal stability in
      patients with low back pain.

PMID- 16648733
TI  - Graft resorption with the use of bone morphogenetic protein: lessons from
      anterior lumbar interbody fusion using femoral ring allografts and recombinant
      human bone morphogenetic protein-2.
AB  - STUDY DESIGN: This is a prospective cohort study examining the results and
      radiographic characteristics of anterior lumbar interbody fusion (ALIF) using
      femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2
      (rhBMP-2). This was compared to a historical control ALIF using FRAs with
      autologous iliac crest bone graft (ICBG). OBJECTIVE: To determine whether the use
      of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs. SUMMARY OF BACKGROUND
      DATA: ALIF is a well-accepted procedure in reconstructive spine surgery. Advances
      in spinal surgery have produced a multitude of anterior interbody implants. The
      rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded
      allograft dowels. The FRA still remains a traditional alternative for anterior
      support. However, as a stand-alone device, the FRA has fallen into disfavor
      because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may
      be more attractive because of its simplicity and remodeling potential. It is
      important to understand the implications when rhBMP-2 is used with such
      structural allografts. METHODS: A total of 36 consecutive patients who underwent
      ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were
      included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP
      2 was followed prospectively. After noticing suboptimal results, the senior
      author terminated this method of lumbar fusion. A total of 27 prior consecutive
      patients who received FRAs filled with autogenous ICBG were used for comparison.
      Analyzing sequential radiographs, flexion-extension radiographs, and computerized
      tomography with multiplanar reconstructions determined nonunions. Minimum follow
      up was 24 months. RESULTS: Pseudarthrosis was identified in 10 of 27 (36%)
      patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was
      higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]).
      Statistical significance was not established because of the early termination of
      the treatment group (P > 0.3). Of interest, radiographs and computerized
      tomography revealed early and aggressive resorption of the FRAs when used with
      rhBMP-2. This preceded graft fracture and even disintegration, resulting in
      instability and eventual nonunion. CONCLUSION: The use of rhBMP-2 did not enhance
      the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a
      higher nonunion rate with rhBMP-2, although this was not significant with the
      numbers available. This result appears to be caused by the aggressive resorptive
      phase of allograft incorporation, which occurs before the osteoinduction phase.

PMID- 16648734
TI  - Operative failure of percutaneous endoscopic lumbar discectomy: a radiologic
      analysis of 55 cases.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the range of lumbar
      disc herniation that can be addressed effectively using current endoscopic
      techniques. SUMMARY OF BACKGROUND DATA: The current technical limitation of the
      procedure in terms of the location and size of the herniation has not been fully
      documented in previous studies. METHODS: The inclusion was an intracanal lower
      lumbar disc herniation in which subsequent surgery was performed because of the
      presence of remnant fragments. All 1586 cases, including 55 failed cases, were
      classified according to the size, location, and extent of migration. RESULTS: In
      the nonmigrated herniations, the central located high-canal compromised (>50%)
      herniations showed the highest rate of failure (15%), and the rate was
      significantly different from the low and high-canal compromise group (1.9% and
      11.1%, respectively, P < 0.001). There was no significant difference in the
      failure rate between the nonmigrated herniations and low-grade migration group
      (2.7% and 3.7%, respectively). However, the high-grade migration group (beyond
      the measured height of the posterior marginal disc space) showed a significantly
      high-incidence of failure (15.7%, P < 0.001). CONCLUSIONS: Based on these
      results, open surgery may be considered for herniations with high-canal
      compromise and high-grade migration. On the other hand, percutaneous endoscopic
      lumbar discectomy can be considered to be a surgical option in the remaining
      intracanal disc herniations.

PMID- 16648735
TI  - Measurement error of lumbar total disc replacement range of motion.
AB  - STUDY DESIGN: A retrospective review of lumbar total disc replacement (TDR)
      radiographs. OBJECTIVE: To determine the error and variability in measuring TDR
      radiographic range of motion (ROM). SUMMARY OF BACKGROUND DATA: Motion
      preservation is the driving force behind lumbar TDR technology. In the recent
      literature, sagittal radiographic TDR ROM as low as 2 degrees has been reported.
      In these studies, ROM was determined by using the Cobb method to measure TDR
      sagittal alignment angles in flexion-extension lateral radiographs. However,
      previous studies in the spinal deformity literature have shown that the Cobb
      method is very susceptible to measurement error. METHODS: There were 5 observers,
      including 2 attending orthopedic spine surgeons, 1 spine fellow, 1 fifth-year
      resident, and 1 fourth-year resident, who measured the ROM of 50 ProDisc II
      (Synthes Spine Solutions, New York, NY) TDRs on standard flexion-extension lumbar
      spine radiograph sets. Repeated measurements were made on 2 occasions using the
      Cobb method. Measurement variability was calculated using 3 statistical methods.
      RESULTS: The 3 statistical methods resulted in extremely similar values for TDR
      ROM observer variability. Overall, the intraobserver variability of TDR ROM
      measurement was +/-4.6 degrees, and interobserver variability was +/-5.2 degrees
      . CONCLUSIONS: To be 95% certain that an implanted TDR prosthesis has any
      sagittal motion, a ROM of at least 4.6 degrees must be observed, which is the
      upper limit of intraobserver measurement variability for a TDR with a true ROM of
      0 degrees. To be 95% certain that a change in TDR ROM has occurred between 2
      measurements by the same observer, a change in ROM of at least 9.6 degrees must
      be observed (the entire range of +/-4.6 degrees intraobserver variability). ROM
      measurement variability should be considered when evaluating the success or
      failure of motion preservation in lumbar TDR.

PMID- 16648736
TI  - Dynamic degenerative lumbar spondylolisthesis: diagnosis with axial loaded
      magnetic resonance imaging.
AB  - STUDY DESIGN: Retrospective review of case notes and imaging. OBJECTIVE: To show
      the advantage of axial loaded magnetic resonance imaging (MRI) for identification
      of dynamic degenerative spondylolisthesis as a suspected cause of spinal
      claudication. SUMMARY OF BACKGROUND DATA: Degenerative spondylolisthesis
      typically occurs at L4/L5 and is usually evident on plain radiography. However,
      dynamic degenerative spondylolisthesis may become evident on erect radiographs
      when not shown on supine radiographs or MRI. METHODS: The case notes and imaging
      (radiography, conventional MRI, and axial loaded MRI) in 2 patients with symptoms
      of spinal claudication were reviewed. RESULTS: A 44-year-old female presented
      with a 3-year history of intermittent low back pain and right leg numbness after
      a fall. A 52-year-old female presented with a 4-year history of low back pain,
      bilateral leg weakness, and right leg numbness. In both cases, conventional MRI
      studies showed mild-to-moderate degenerative disc disease only with no evidence
      of abnormal spinal alignment or nerve root compression. Axial loaded MRI clearly
      showed the development of a degenerative spondylolisthesis with central canal
      stenosis and facet ganglion formation in 1 case. CONCLUSIONS: Axial loaded MRI
      identified occult dynamic degenerative spondylolisthesis, which correlated with
      the clinical picture but was not shown on initial conventional MRI or plain
      radiography.

PMID- 16648737
TI  - Surgical treatment of scoliosis in larsen syndrome with bilateral hip
      dislocation.
AB  - STUDY DESIGN: This is a report of a 12-year-old girl treated surgically for
      scoliosis associated with bilateral hip dislocation in Larsen syndrome.
      OBJECTIVE: To describe a rare case of scoliosis associated with Larsen syndrome
      and bilateral hip dislocation that was treated surgically with follow-up for 15
      years. SUMMARY OF BACKGROUND DATA: There are few reports of the long-term follow
      up of cases involving surgically treated scoliosis associated with bilaterally
      dislocated hips. METHODS: The patient's spine showed a right thoracic curve (T5
      T12) with a Cobb angle of 77 degrees and did not show pelvic obliquity on an
      anterior-posterior radiograph film. On the sagittal alignment of her spine, the
      thoracic spine showed an abnormal lordosis (T5-T12: 19 degrees), and the lumbar
      spine had a hyperlordosis (L1-S1: 57 degrees) with a large lumbosacral angle (72
      degrees ). We performed a posterior spinal fusion between T4 and L2 using Cotrel
      Dubousset Instrumentation, anticipating the restoration of normal lumbar and
      cervical lordosis, as well as thoracic kyphosis. RESULTS: The Cobb angle of
      thoracic scoliosis improved from 77 degrees to 28 degrees, and a thoracic
      kyphosis of 12 degrees (T5-T12) was obtained. Subsequently, on the sagittal
      plane, the lumbosacral angle (sacral anteflexion) decreased from 72 degrees to 52
      degrees, comparable to that of patients with hip dislocation, and the lumbar
      lordotic angle increased from 57 degrees to 66 degrees. The restoration of
      thoracic kyphosis resulted in an increase of lumbar lordosis and decrease of
      sacral anteflexion. At the 15-year follow-up,although the thoracic scoliosis (T5
      T12) had increased to 36 degrees, good coronal and sagittal balance had been
      maintained. The patient is asymptomatic in her spine and hip. CONCLUSIONS: A case
      of scoliosis associated with dislocated hips in a patient with Larsen syndrome
      was successfully treated with posterior correction surgery. Fusion surgery
      between T4 and L2 provided an ideal sagittal balance of the total spine, while
      preserving 4 lumbar mobile segments.

PMID- 16648739
TI  - A prospective randomized study of posterolateral lumbar fusion using osteogenic
      protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of
      surgical exploration and histologic assessment.
AB  - STUDY DESIGN: A prospective, randomized and controlled study. OBJECTIVES: To
      evaluate the osteoinductive property of Osteogenic Protein-1 (OP-1 or BMP-7) and
      fusion rate in human instrumented posterolateral lumbar fusion through
      radiographic examination, surgical exploration, and histologic assessment.
      SUMMARY OF BACKGROUND DATA: The use of osteoinductive agents is a current topic
      in spinal fusion. Numerous preclinical investigations have demonstrated efficacy
      of osteoinductive proteins in spinal fusion, but few human clinical studies have
      been reported. METHODS: Nineteen patients with L3-L4 or L4-L5 degenerative
      spondylolisthesis underwent posterolateral lumbar fusion using pedicle screw
      instrumentation. The patients were randomized to receive either OP-1 Putty (3.5
      mg OP-1/g of collagen matrix per side) alone (n = 9), or local autograft with HA
      TCP granules (n = 10). Fusion status was evaluated using plain radiography and CT
      scan. Radiographic fusion criteria included less than 5 degrees of angular
      motion, less than 2 mm of translation, and evidence of bridging bone in the
      posterolateral lumbar area in which the graft materials were placed following
      decortication. After a minimum 1-year follow-up, the patients who showed
      radiographic evidence of fusion underwent instrumentation removal and surgical
      exploration of the fusion site. Biopsy specimens were taken from the fusion mass
      and evaluated histologically. RESULTS: Radiographic fusion rate was 7 of 9 OP-1
      patients and 9 of 10 control patients. Based on surgical exploration of these 16
      patients, new bone formation was macroscopically observed in the posterolateral
      lumbar region in all cases; however, solid fusion was observed in 4 of 7OP-1 and
      7 of 9 HA-TCP/autograft patients. Histologic assessment demonstrated viable bone
      in 6 of 7 OP-1 patients. All the control (HA-TCP/autograft) specimens contained
      viable bone and fibrous tissue surrounding ceramic granules, suggesting slow
      incorporation of the graft material. CONCLUSIONS: In a human posterolateral
      lumbar spine trial, OP-1 reliably induced viable amounts of new bone formation,
      but the fusion success rate evaluated by surgical exploration was only 4 of 7.

PMID- 16648740
TI  - The effectiveness of high-intensity versus low-intensity back schools in an
      occupational setting: a pragmatic randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To compare high- and low
      intensity back schools with usual care in occupational health care. SUMMARY OF
      BACKGROUND DATA: The content and intensity of back schools vary widely and the
      methodologic quality of randomized controlled trials is generally weak. Until
      now, no back school has proven to be superior for workers sick-listed because of
      subacute nonspecific low back pain. METHODS: Workers (n = 299) sick-listed for a
      period of 3 to 6 weeks because of nonspecific low back pain were recruited by the
      occupational physician and randomly assigned to a high-intensity back school, a
      low-intensity back school, or care as usual. Outcome measures were days until
      return to work, total days of sick-leave, pain, functional status, kinesiophobia,
      and perceived recovery and were assessed at baseline and at 3 and 6 months of
      follow-up. Principal analyses were performed according to the intention-to-treat
      principle. RESULTS: We randomly allocated 299 workers. Workers in the low
      intensity back school returned to work faster compared with usual care and the
      high-intensity back school, with hazard ratios of 1.4 (P = 0.06) and 1.3 (P =
      0.09), respectively. The comparison between high-intensity back school and usual
      care resulted in a hazard ratio of 1.0 (P = 0.83). The median number of sick
      leave days was 68, 75, and 85 in the low-intensity back school, usual care, and
      high-intensity back school, respectively. Beneficial effects on functional status
      and kinesiophobia were found at 3 months in favor of the low-intensity back
      school. No substantial differences on pain and perceived recovery were found
      between groups. CONCLUSIONS: The low-intensity back school was most effective in
      reducing work absence, functional disability, and kinesiophobia, and more workers
      in this group scored a higher perceived recovery during the 6-month follow-up.

PMID- 16648741
TI  - A randomized controlled trial investigating the efficiency of musculoskeletal
      physiotherapy on chronic low back disorder.
AB  - STUDY DESIGN: Randomized, single blind, controlled trial. OBJECTIVE: To determine
      the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back
      disorder. SUMMARY OF BACKGROUND DATA: Musculoskeletal physiotherapy encompasses
      many treatment methods, however, manual therapy and exercises to rehabilitate
      spinal stabilization are the most frequently used. Despite their popularity,
      scant evidence supports their use on subjects with chronic low back disorder.
      METHODS: A total of 346 subjects were randomized to manual therapy, a 10-week
      spinal stabilization rehabilitation program, or a minimal intervention control
      group. Data were collected at baseline, and 3, 6, 12, and 24 months after
      intervention. Outcome measures recorded intensity of low back pain, disability,
      handicap, medication, and quality of life. There were 4 main variables combined
      in a primary component analysis to form a single outcome measure (i.e., a measure
      of dysfunction). RESULTS: The results indicated statistically significant
      improvements in favor of the spinal stabilization group at the 6-month stage in
      pain (65.9% reduction in symptoms) and dysfunction (combined mean reduction of
      134, standard error 23.84), and at the 1-year stage in medication (34.3%
      reduction in medication), dysfunction (combined mean reduction of 134, standard
      error 18.2), and disability (mean difference in change 15.71 Oswestry Disability
      Index, 95% confidence interval 19.3-10.01). CONCLUSIONS: As a component of
      musculoskeletal physiotherapy, the spinal stabilization program is more effective
      than manually applied therapy or an education booklet in treating chronic low
      back disorder over time. Both manual therapy and the spinal stabilization program
      are significantly effective in pain reduction in comparison to an active control.
      To our knowledge and up until now, this result has not been shown in patients
      with chronic low back disorder.

PMID- 16648742
TI  - Notochord cells regulate intervertebral disc chondrocyte proteoglycan production
      and cell proliferation.
AB  - STUDY DESIGN: Non-chondrodystrophic dog notochord cell conditioned medium was
      used to evaluate chondrocyte proteoglycan production and cell proliferation.
      OBJECTIVES: To evaluate the responsiveness of bovine disc-derived chondrocytes to
      notochord-cell conditioned medium with respect to proteoglycan and cell
      proliferation. In addition, to examine phenotypic changes of notochord cells
      cultured in monolayered as compared to 3-dimensional culture. SUMMARY OF
      BACKGROUND DATA: Non-chondrodystrophic dogs maintain their intervertebral disc
      notochord cells into adulthood and are protected from having degenerative disc
      disease develop. The chondrodystrophic breeds such as beagles do not preserve
      these cells and have disc disease develop much earlier in life. The role of the
      notochord cell within the disc nucleus is poorly understood. METHODS: Canine
      notochord cells were cultured within alginate beads in serum-deficient conditions
      using Dulbecco modified Eagle medium to produce notochord cell conditioned medium
      (NCCM). NCCM was used to stimulate bovine disc chondrocytes from which we
      evaluated proteoglycan production and cell proliferation as compared to
      chondrocytes grown in DMEM alone. In addition, parallel cultures of notochord
      cells were seeded within alginate beads as well as in monolayer and cultured in
      order to examine for differences in phenotype between the 2 culture conditions.
      RESULTS: The morphologic aspects of the intervertebral disc between the species
      differed markedly. A dose- dependent relationship was seen between proteoglycan
      production and NCCM concentration across various concentrations of NCCM in
      repeated experiments. Although there was a 4-fold increase in cell proliferation
      under all NCCM concentrations, this increase in cell proliferation was not dose
      dependent in the concentrations tested. Unlike chondrocytes, notochord cells do
      not adhere to tissue culture plate (monolayer) until at least day 4-6, do not
      markedly alter their phenotype, and rapidly assume masses of cells while floating
      within tissue culture medium. CONCLUSIONS: The biology of the disc-derived
      chondrocyte is profoundly affected by NCCM in that various concentrations of NCCM
      activate proteoglycan production in a dose-dependent fashion. However, in the
      doses tested in our study, cell proliferation was increased but in a nondose
      dependent fashion. Notochord cells retain their phenotype even in monolayer and
      through the development of floating intimately associated masses of cells suggest
      the development and maintenance of cell-cell interaction. These masses of cells
      are retained even after 6 days in culture when they do attach to the tissue plate
      surface. The persistence of notochord cells in non-chondrodystrophic dog species
      suggests that these in vitro studies may mirror the milieu of the disc in vivo,
      in which the notochord cell may play a key role in disc homeostasis.

PMID- 16648743
TI  - Effects of COX-2 and iNOS inhibitors alone or in combination with olfactory
      ensheathing cell grafts after spinal cord injury.
AB  - STUDY DESIGN: We studied the effects of inhibitors of COX-2 (NS398) and iNOS
      (aminoguanidine) alone or in combination with olfactory ensheathing cell (OEC)
      grafts after spinal cord injury in the rat. OBJECTIVE: To assess the role exerted
      by COX-2 and iNOS after spinal cord injury and an OEC transplant. SUMMARY OF
      BACKGROUND DATA: COX-2 and iNOS exert a detrimental effect after spinal cord
      injury. In contrast, OECs grafted into the injured spinal cord mediate
      neuroprotection and also promote the up-regulation of COX-2 and iNOS. METHODS:
      Photochemical injury was induced at T8 spinal cord segment. Rats received local
      injection of OECs (n = 15) or vehicle (DMEM; n = 15). Six subgroups of rats (n =
      5 rats each) were given NS398 (DM-NS; OEC-NS), aminoguanidine (DM-AG; OEC-AG), or
      saline (DM-SS; OEC-SS). Locomotor ability, pain sensibility, tissue sparing, and
      density of blood vessels were evaluated. RESULTS: Two weeks following injury,
      motor skills and nociceptive response were significantly higher in DM-NS and DM
      AG than in DM-SS rats. The area of preserved spinal cord parenchyma was higher in
      treated animals than in those given saline. In contrast, functional outcome,
      tissue sparing, and density of blood vessels were lower in OEC-NS and OEC-AG than
      in OEC-SS animals. CONCLUSIONS: These results suggest that, although COX-2 and
      iNOS exert a detrimental role after spinal cord injury, they may play an
      important role in the neuroprotective mechanisms induced by OEC grafts after
      spinal cord injury.

PMID- 16648744
TI  - A cadaveric examination of pediatric cervical pedicle morphology.
AB  - STUDY DESIGN: A retrospective radiographic analysis of 47 intact cadaver
      pediatric cervical spines at the Hamann-Todd Osteology Collection in Cleveland,
      Ohio. OBJECTIVES: Evaluate the morphology of the pediatric cervical spine
      pedicle, the feasibility of surgical pedicle screw instrumentation, and examine
      the contribution of growth to the pedicle axis. SUMMARY OF BACKGROUND DATA: The
      adult cervical spine has been studied extensively and the morphology of the
      pedicles well documented. The morphology of the pediatric cervical, thoracic, and
      thoracolumbar spine has been studied radiographically, but, to our knowledge, no
      study has specifically examined the cervical spine pedicle, pedicle axis, and
      their changes with growth. METHODS: A total of 47 pediatric human cadaver spines
      with a mean age of 13 years (range 3-18 years at death) from the Hamann-Todd
      Osteology Collection at the Cleveland Museum of Natural History were analyzed
      radiographically. There were 25 females and 22 males. The C3-C7 vertebrae were
      used in this study. The 228 vertebral specimens were evaluated in the axial and
      sagittal planes. The radiographs were subsequently digitized and measured for 5
      parameters on the axial view: pedicle axis length, pedicle length, pedicle width,
      cervical spinal canal anteroposterior spinal canal diameter, and interpedicular
      distance. RESULTS: The pedicle axis length increased with advancing age. The
      pedicle length remained relatively constant throughout growth, and the pedicle
      diameter showed a statistically significant increase with growth. Mean pedicle
      diameter width was 3.0 mm at C3 and 4.2 mm at C7 in the 3-5 year-old group
      compared to 4.3 mm and 6.1 mm, respectively, at C3 and C7 at 18 years of age. The
      anteroposterior spinal canal diameter remained relatively constant with
      increasing age. The interpedicular distance achieved 80% of its adult size by 3-5
      years of age. Regarding pedicle axis growth, the 3 components of the pedicle axis
      (i.e., vertebral body, pedicle, and lateral mass) were analyzed with regards to
      their contribution to growth. The vertebral body contributed an increasing
      percentage to overall pedicle axis growth with age, while the pedicle itself
      contributed a progressively smaller percentage. CONCLUSIONS: Our results showed
      an overall increase in the pedicle axis and pedicle width but no significant
      change in pedicle length. The data in this study indicate that pedicle screws may
      not be safe for use in the pediatric cervical spine, particularly younger
      children. The use of lateral mass screws was not specifically addressed in this
      study. As in the thoracolumbar spine, growth of the pedicles in relation to the
      spinal canal is lateral to the canal. The vertebral body itself appears to
      contribute most to overall pedicle axis growth, while the pedicle itself
      contributes a progressively smaller percentage over time.

PMID- 16648745
TI  - Percutaneous vertebroplasty: functional improvement in patients with osteoporotic
      compression fractures.
AB  - STUDY DESIGN: Prospective, double-cohort study. OBJECTIVE: To evaluate
      conservative and percutaneous vertebroplasty (PV) management of osteoporotic
      vertebral fractures. SUMMARY OF BACKGROUND DATA: PV is an elective alternative to
      conservative management for the treatment of a painful osteoporotic vertebral
      fracture. METHODS: We performed a prospective study consisting of 101 consecutive
      patients who underwent PV and 27 patients who refused PV treatment and were
      managed conservatively. We used a data evaluation and outcomes system that was
      developed to evaluate the outcomes of surgical intervention. RESULTS: Patients
      that elected for PV as a treatment of their fractures had significantly more pain
      and functional impairment before the procedure than the patients of the
      conservative group (P < 0.001). The pain, functional, and general health scores
      of the PV group were improved from the preoperative mean values (P < 0.001) in
      all postoperative periods. Compared with the conservative treatment group, there
      was a significant difference at month 3. However, no statistical differences on
      function were observed between these groups at 6 months and 1 year posttreatment.
      CONCLUSIONS: PV demonstrated a rapid and significant relief of pain and improved
      the quality of life. PV election for treatment of painful osteoporotic vertebral
      fracture after 6 weeks of conservative treatment was based on pain and functional
      impairment.

PMID- 16648746
TI  - Point of view: the honest truth about vertebroplasty.

PMID- 16648747
TI  - Intradiscal cement leak following percutaneous vertebroplasty.
AB  - STUDY DESIGN: A retrospective study to detect patients with cement leakage into
      the disc space following vertebroplasty. OBJECTIVE: To determine the frequency,
      causes, and clinical significance of cement leakage into the disc space. SUMMARY
      OF BACKGROUND DATA: Much has been written about cement leakage into the epidural
      space following vertebroplasty but only little about intradiscal leakage.
      METHODS: A total of 66 patients with 1 cemented osteoporotic, fractured vertebra
      between T5 and L5 were followed for at least 2 years. Two of the senior authors
      (Y.M. and A.P.) evaluated independently cement leakage into the disc space,
      possible causes were investigated, and the clinical results were evaluated
      according to patient self-assessment. RESULTS: Detected in 27 patients, cement
      leakage into the disc space did not negatively affect patient satisfaction with
      the procedure. In 7 of these patients, leakage occurred through an intravertebral
      vacuum cleft and, in 8, through a perforation of the endplate created by the
      needle tip. In only 2 patients was cement found to cross the height of the
      vertebral body and leak into the contralateral disc. CONCLUSIONS: Apart from
      iatrogenic endplate perforation, cement extravasation into the disc space was
      always found to occur through the fractured endplate or a vacuum cleft. Placing
      the needle tip far from the fractured endplate and using more solid cement appear
      to decrease the risk of leakage.

PMID- 16648748
TI  - Paragliding accidents with spinal cord injury: 10 years' experience at a single
      institution.
AB  - STUDY DESIGN: A retrospective analysis of 41 patients with spinal cord injury
      (SCI) after paragliding accidents. OBJECTIVE: To determine the lesioned pattern
      and prognostic radiologic factors for rehabilitation potential. SUMMARY OF
      BACKGROUND DATA: Paragliding accidents with SCI present a new injury pattern,
      dealt with in the current literature from a purely orthopedic, sports medicine,
      or insurance point of view. Few combinations of orthopedic and neurologic data
      are available. METHODS: Over a 10-year period, the case records of 41 patients
      with SCI caused by paragliding accidents were analyzed with regard to vertebral
      and other skeletal fractures, neurologic recovery (American Spine Injury
      Association score), and professional reintegration. RESULTS: Vertebral fractures
      peaked in the thoracolumbar region, with L1 most frequently (30%) affected. The
      levels of vertebral lesion and neurologic deficit differed in 32% of patients.
      Combination with lower-limb fractures was characteristic for paragliding SCI (P <
      0.001); 93% of patients with initial bony occlusion of the spinal canal of <70%
      left the clinic ambulatory. CONCLUSION: Paragliding accidents with SCI show a
      characteristic injury pattern associated with a high recovery potential if the
      initial bony spinal canal occlusion is <70%. Half the patients will reintegrate
      in their former profession and place of employment.

PMID- 16648749
TI  - Association of estrogen receptor gene polymorphisms with susceptibility to
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A case-control study is presented. OBJECTIVE: To investigate the
      association of estrogen receptor gene polymorphisms with adolescent idiopathic
      scoliosis (AIS) risk. SUMMARY OF BACKGROUND DATA: Previous studies have shown
      that genetic factors are important in the pathogenesis of idiopathic scoliosis.
      Only 1 publication suggested that XbaI site polymorphism was associated with
      curve severity of idiopathic scoliosis. However, to our knowledge, the
      relationship of estrogen receptor gene polymorphisms and the individual
      susceptibility to idiopathic scoliosis has not been studied. METHODS: This study
      included 202 patients with AIS and 174 healthy controls. Height, menarche status,
      curve pattern, Cobb angle, and Risser sign in female patients were recorded.
      There were 2 polymorphic loci, PvuII and XbaI locus, of estrogen receptor
      analyzed by restriction fragment length polymorphisms. RESULTS: The frequency of
      XX genotype was significantly higher in patients than that in controls (P =
      0.005). The X allele appeared to be overrepresented in patients compared with
      controls (P = 0.001). Furthermore, the frequencies of XX genotype in female
      patients whose height was > or = 160 cm and Cobb angle > or = 40 degrees were
      higher than those whose height was <160 cm and Cobb angle <40 degrees (P = 0.001
      and P < 0.001, respectively). CONCLUSIONS: The XbaI site polymorphism of estrogen
      receptor gene may be associated with a risk of AIS.

PMID- 16648750
TI  - Sagittal translation in opening wedge osteotomy for the correction of
      thoracolumbar kyphotic deformity in ankylosing spondylitis.
AB  - STUDY DESIGN: Retrospective. OBJECTIVES: To document sagittal translation (ST) of
      the vertebral column in opening wedge osteotomy (OWO) for ankylosing spondylitis
      (AS) kyphosis. SUMMARY OF BACKGROUND DATA: Surgeons recognize displacement at the
      hinge of correction in OWO as an accidental event between the vertebrae on the
      side of OWO rather than ST of the cranial or caudal vertebral column. No report
      documents ST in this context. METHODS: We evaluated radiographic and clinical
      results in 127 patients (aged 17-49 years) for ST, or displacement of more than 2
      mm between the cranial and caudal vertebral columns at the OWO level, over 5
      years. RESULTS: Thirty-four (27%) patients had ST. In 31 (94%), the kyphotic apex
      was at T11 to L4. ST was positively correlated with the correction of lumbar
      lordosis and preoperative lumbar kyphosis. Five (15%) of 34 patients with ST had
      neurologic complications compared with 2 (2%) of 93 who did not. CONCLUSIONS: ST
      is a basic mechanism for correcting sagittal imbalance and is likely to occur
      when the level of OWO is near the apex of deformity. Patients needing more
      correction of lumbar lordosis than others for best correction of sagittal
      imbalance need ST more to join the mechanism of correction.

PMID- 16648751
TI  - Association of the Taq I allele in vitamin D receptor with degenerative disc
      disease and disc bulge in a Chinese population.
AB  - STUDY DESIGN: Large scale, case-control study. OBJECTIVE: To assess the effect of
      the Taq I alleles in vitamin D receptor on the risk of developing degenerative
      disc disease in a Southern Chinese population. SUMMARY OF BACKGROUND DATA:
      Previous studies in Finns and Japanese suggest that the Taq I polymorphism of
      vitamin D receptor is associated with the development of degenerative disc
      disease in the lumbar spine. However, sample sizes were small, and the results
      need to be confirmed in other populations. METHOD: Lumbar degenerative disc
      disease was defined by magnetic resonance imaging (MRI) on 804 Southern Chinese
      volunteers between 18 and 55 years of age. Restriction enzyme digestion of
      polymerase chain reaction products was used to analyze the Taq I alleles. The
      resulting genotypes were correlated with the presence of lumbar disc degeneration
      and bulge on MRI. RESULTS: Using logistic regression analysis and adjusting for
      age and sex, the t allele of Taq I in vitamin D receptor gene was significantly
      associated with degenerative disc disease, with an odds ratio (OR) of 2.61 (95%
      confidence interval [CI] 1.15-5.90, P = 0.041). Further subgroup analysis showed
      that in individuals younger than 40 years, the OR was even higher, at 5.97 (95%
      CI 1.69-21.15, P = 0.002). Similarly, disc bulge was significantly associated
      with t allele (OR = 7.17, 95% CI 1.43-36.01, P = 0.001) in individuals younger
      than 40 years. Anular tears and the Schmorl nodes were not associated with the t
      allele of Taq I polymorphism. CONCLUSION: To our knowledge, this is the largest
      scale genetics study to date using MRI to define precisely degenerative disc
      disease in the Southern Chinese population. We showed that the t allele of
      vitamin D receptor Taq I is associated with a high risk of degenerative disc
      disease and disc bulge developing, especially in individuals younger than 40
      years.

PMID- 16648752
TI  - Epidemiology of back pain in a representative cohort of Italian persons 65 years
      of age and older: the InCHIANTI study.
AB  - STUDY DESIGN: Clinico-epidemiologic study in the Chianti area (Tuscany, Italy).
      OBJECTIVES: To describe prevalence and correlates of back pain in a
      representative sample of the population. SUMMARY OF BACKGROUND DATA: Back pain is
      common in old age and is related to functional limitations, but back pain
      characteristics and correlates in older adults, which may be targeted by specific
      interventions, are still underinvestigated. METHODS: A total of 1,299 persons
      aged 65 or older were selected from the city registry of Greve in Chianti and
      Bagno a Ripoli; 1,008 (565 women; 443 men) were included in this analysis. Back
      pain in the past 12 months was ascertained using a questionnaire. Potential
      correlates of back pain were identified in age- and sex-adjusted regression
      analyses, and their independent association with back pain was tested in a
      multivariate model. RESULTS: The prevalence of frequent back pain was 31.5%. Back
      pain was reported less often by men and the very old, was primarily located in
      the dorsolumbar and lumbar spine, was moderate in intensity and mainly elicited
      by carrying, lifting, and pushing heavy objects. Among participants who reported
      frequent back pain, 76.3% had no back pain-related impairments; 7.4% of the
      overall study population had back pain-related functional limitation. Back pain
      participants were significantly more likely to report difficulty in heavy
      household chores, carrying a shopping bag, cutting toenails, and using public
      transportation. Limited trunk extension, depression, low levels of prior-year
      physical activity, and hip, knee, and foot pain were independent correlates of
      back pain. CONCLUSIONS: Frequent back pain is highly prevalent in the older
      population and is often associated with conditions that are potentially
      reversible.

PMID- 16648753
TI  - Prevalence of psychiatric disorders in patients with chronic disabling
      occupational spinal disorders.
AB  - STUDY DESIGN: A prevalence study. OBJECTIVES: To assess the prevalence of
      psychiatric disorders among a large group of patients with chronic disabling
      occupational spinal disorders (CDOSDs), using a reliable and valid diagnostic
      instrument. SUMMARY OF BACKGROUND DATA: Although unrecognized and untreated
      psychiatric disorders have been found to interfere with successful treatment of
      CDOSD patients, little data are currently available regarding the psychiatric
      characteristics of patients claiming work-related injuries that result in CDOSDs.
      METHODS: Psychiatric disorders in a consecutive group of CDOSD patients (n =
      1,323) attending a tertiary referral center for patients with CDOSD were
      diagnosed using the Diagnostic and Statistical Manual of Mental Disorders.
      RESULTS.: Overall prevalence of psychiatric disorders was found to be
      significantly elevated in CDOSD patients compared with base rates in the general
      population. A majority (65%) of patients were diagnosed with at least one current
      disorder (not including Pain Disorder, which is nearly universal in this
      population), compared with only 15% of the general population. Major Depressive
      Disorder (56%), Substance Use Disorders (14%), Anxiety Disorders (11%), and Axis
      II Personality Disorders (70%) were the most common diagnoses. CONCLUSIONS:
      Clinicians treating CDOSD patients must be aware of the high prevalence of
      psychiatric disorders in this population. They must also be prepared to use
      mental health professionals to assist them in identifying and stabilizing these
      patients. Failure to follow a biopsychosocial approach to treatment will likely
      contribute to prolonged disability in a substantial number of these chronic pain
      patients.

PMID- 16648754
TI  - Risk factor for unsatisfactory outcome after lumbar foraminal and far lateral
      microdecompression.
AB  - STUDY DESIGN: A retrospective study of consecutive patients who underwent
      microdecompression for far lateral disc or foraminal stenosis. OBJECTIVES: To
      evaluate the risk factors for unsatisfactory outcome. SUMMARY OF BACKGROUND DATA:
      There has been no detailed analysis of postoperative radicular pain, although it
      is not infrequent following foraminal and far lateral microdecompression.
      METHODS: A total of 184 patients, who were followed up for more than 2 years,
      were reviewed. Microdecompression was performed through lateral intermuscular
      approach. In cases of double herniation (combination of intracanalicular disc at
      the same level), additional intracanalicular decompression was simultaneously
      performed. The unsatisfactory outcomes included persistent or recurrent leg pain,
      based on the Japanese Orthopedic Association leg pain score, and revision surgery
      at the same level. The potential risk factors, including gender, age, symptom
      period, preoperative radiologic and intraoperative findings, were determined.
      RESULTS: The average follow-up period was 38.4 months, with a maximum 70 months.
      Forty of the 184 patients (21.7%) had persistent or recurrent leg pain, with nine
      requiring revision surgeries. The statistically significant risk factor for
      unfavorable outcomes was double herniation, with odds ratio of 2.89 (P = 0.004).
      CONCLUSION: Facet preserving microdecompression is an effective method for
      foraminal and far lateral root compression. However, in cases of double
      herniation, total facetectomy is preferable.

PMID- 16648755
TI  - Diagnosis of lumbar spinal stenosis: a systematic review of the accuracy of
      diagnostic tests.
AB  - STUDY DESIGN: Systematic review of diagnostic studies. OBJECTIVE: To investigate
      the diagnostic performance of tests used to detect lumbar spinal stenosis.
      SUMMARY OF BACKGROUND DATA: Little is known about the diagnostic accuracy of
      tests in detecting lumbar spinal stenosis. A systematic review will provide more
      insight in this topic. METHODS: We performed a literature search in Medline
      (PubMed) and Embase for original diagnostic studies on lumbar spinal stenosis, in
      which one or more different tests were evaluated with a reference standard, and
      diagnostic values were reported or could be calculated. Two reviewers
      independently checked all abstracts and full text articles for inclusion
      criteria. Included articles were assessed for their quality using the Quadas
      tool. Study features and diagnostic values were extracted from the included
      studies. RESULTS: Of the 24 articles included in this review, 15 concerned
      imaging tests, 7 evaluated "clinical tests," and 2 reported on other diagnostic
      tests. The overall quality was poor; only 5 studies scored positive on more than
      50% of the quality items. Estimates of the diagnostic value of the tests differed
      considerably. The imaging studies showed no superior accuracy for myelography
      compared with CT or MRI. Overall, there is considerable variation in the clinical
      tests; some studies show high sensitivity, whereas others show high specificity.
      CONCLUSIONS: Because of heterogeneity and overall poor quality, no firm
      conclusions about the diagnostic performance of the different tests can be drawn.
      Better-designed studies exploring the accuracy of diagnostic tests are needed to
      improve the diagnostic policy.

PMID- 16648756
TI  - A case report of coexistence of a sialolith and an adenoid cystic carcinoma in
      the submandibular gland.
AB  - The occurrence of sialoliths in the submandibular gland is 80% due to the
      specific anatomy of both the gland and its duct. The diagnosis is rather easy
      because of the obvious clinical signs of the entity. Imaging studies are always
      necessary in order to treat the patient as effectively as possible. The stones do
      not tend to occur within the gland as frequently as in the respective duct. The
      coexistence of sialoliths and malignant tumors is extremely rare. A 70-year-old
      woman with intraparenchymal stone was operated in our ENT department. In addition
      to the sialolith the pathological examination revealed the existence of an
      adenoid cystic carcinoma (ACC), that extended to the neighboring skeletal muscle.
      This is the reason why we believe it would be useful to report this case of a
      large stone (14 mm in diameter) located in the submandibular gland coexisting
      with ACC. This case report is a very good example illustrating that all available
      means should be used prior to reaching a conclusion and making a health
      professional decision.

PMID- 16648757
TI  - Brachytherapy in lip cancer.
AB  - Lip cancer is one of the most prevalent skin tumours of the head and neck. The
      characteristics of the tumour relate to their exophyitic growth in an area of
      easy visual acces which allows their diagnosis in early stages. As a result,
      there is a better prognosis with the present treatments. In early stages the
      treatment can be performed by surgery or by brachytherapy, and the results are
      similar on local control; nevertheless brachytherapy offers the best functional
      and esthetic results. We are reporting on a review of the literature in relation
      to indications, techniques and results of brachytherapy for lip cancer.

PMID- 16648758
TI  - Oral cancer mortality in the province of Cordoba, Argentine Republic in the
      period 1975-2000. A comparative study with other populations.
AB  - Malignant neoplasm (MN) mortality worldwide ranks among the first four causes of
      death, in the 1990 decade (1-4). The aim of this work is to study the eight most
      frequent MN mortality rates, and especially that one caused by oral cancer (OC)
      in the province of Cordoba, Argentine Republic, in the period between 1975 and
      2000, in order to analyze its characteristics and compare with other populations
      in America and Europe. MATERIAL AND METHODS: The data were provided by the
      provincial and national Health Ministry and Globocan 2000. RESULTS: The highest
      male rates were those of Slovakia and France, prevailing lung and bronchus
      tumors; whereas in females the highest rate was that of breast cancer in the
      United Kingdom and Germany, and lung cancer in the United States. Regarding to OC
      in the populations under study, Slovakia and France held the highest rates for
      both sexes, being Cordoba and Argentina among the lowest values, especially in
      women. Tongue was the most frequent site in Cordoba (43.5%), followed by salivary
      glands (23.7%). Male prevailed over female and the oldest ages were observed in
      the period 1995-2000. The mortality rates by MN in all sites increased 6.6% in
      both sexes, and by OC 77% in women within the period under study in Cordoba. Oral
      cancer is a serious problem for public health causing great morbidity and
      mortality, a situation that has not improved in decades. Mortality rates are an
      important tool towards implementation and planning of health policies and
      programs for cancer prevention.

PMID- 16648759
TI  - Cockayne's syndrome: a case report. Literature review.
AB  - Cockayne s syndrome is a genetic disorder with a recessive autosomal inheritance,
      described first by Cockayne in 1936. Patients with this syndrome present failure
      to thrive, short stature, premature aging, neurological alterations,
      photosensitivity, delayed eruption of the primary teeth, congenitally absent of
      some permanent teeth, partial macrodontia, atrophy of the alveolar process and
      caries. It could be caused by two gene mutations, CNK1 (ERCC8) and ERCC6, located
      on the 5 and 10 chromosomes respectively, causing two variations of Cockayne s
      syndrome, CS-A, secondary to a ERCC8 mutation and CS-B with ERCC6 mutation, the
      last one causes hypersensitivity to the ultraviolet light secondary to a DNA
      repair defect. The syndrome is also associated with mutations of the XPB, XPD and
      XPG genes. In this report we present a 9 year and 4 month old patient. He had a
      height of 94 cm, weight of 8.6 Kg, head circumference of 42 cm. and blood
      pressure of 120/80. Cachectic habitus, kyphosis, microcephaly, oval face, sunken
      eyes, a thin and beaklike nose, lack of subcutaneous facial fat (especially in
      the middle of the face), and large ears give the patient a birdlike appearance.
      It is notorious the photosensitivity in all the sun-exposed skin. The patient
      also displays delayed psychomotor skills and mental retardation. In the oral
      cavity we found deficient hygiene, gingivitis, cervical caries, enamel
      hipoplasia, abnormal position of the upper and inferior lateral incisors,
      macrodontia of the upper central teeth, the left one presented a caries. In the x
      ray we observed congenital absence of 14, 23 and 24 teeth and mandibular
      hipoplasia. The aim of this review is to show the dentistry community the
      characteristics of the Cockayne s syndrome by means of a clinical case.

PMID- 16648760
TI  - Palatine perforation induced by cocaine.
AB  - Worldwide, the use of cocaine has an increased over the years, various secondary
      effects have been described. Here we present a 48 years old female with a 2-month
      evolution bucconasal ulcer in the hard palate induced by cocaine usage
      accompanied by swallow and phonation dysfunctions. Ethiopathogenesis,
      differential diagnoses and treatment are discussed.

PMID- 16648761
TI  - Fibrosarcoma originating in the mandible.
AB  - Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely
      affects the oral cavity and can cause local recurrences or metastasis. In this
      article we describe a case of primary fibrosarcoma in the mandible in a 16-year
      old girl. Microscopically the tumor showed an intense proliferation of spindle
      shaped cells, varying little in size and shape and arranged in parallel bands,
      partly crossing each other, the mitotic activity was increased and there was
      nuclear pleomorphism. Immunohistochemically the cells only showed
      immunoreactivity for vimentin and negativity for S-100 protein, CD 68,
      cytokeratin cocktail, HMB-45, CD34, pan actin HHF 35, desmin, smooth muscle actin
      and epithelial membrane antigen (EMA). Based on clinical, radiological,
      histological and immunohistochemical findings the final diagnosis was high-grade
      intra-osseous fibrosarcoma. The treatment choice was radical surgery with
      mandibular reconstruction. After one year and nine months of the treatment the
      patient displayed multiple metastases. Radiation therapy and chemotherapy were
      used as adjuvant treatment. Unfortunately, the girl died two years after initial
      diagnosis.

PMID- 16648762
TI  - Expression of betacatenin in carcinoma in pleomorphic adenoma, pleomorphic
      adenoma and normal salivary gland: an immunohistochemical study.
AB  - OBJECTIVES: Pleomorphic adenomas are the most frequent type of epithelial
      salivary gland neoplasms, and their malignant counterpart, the carcinoma in
      pleomorphic adenomas, is much less common. Beta-catenin is a cell adhesion
      molecule associated with the invasion and metastasis of carcinomas of the head
      and neck, esophagus. The objective of this study was to detect the expression of
      beta-catenin in pleomorphic adenomas, carcinomas in pleomorphic adenomas and
      normal salivary glands to discuss its role in the development of these two
      lesions. STUDY DESIGN: The expression of beta-catenin (BD Transduction
      Laboratories) was analyzed by immunohistochemistry in formalin-fixed, paraffin
      embedded specimens by the avidin-biotin-peroxidase complex method in 16
      pleomorphic adenomas (12 from minor salivary glands), 3 carcinomas in pleomorphic
      adenomas (all from palate) and 10 normal salivary glands as control group (5 from
      major and 5 from minor salivary glands). RESULTS: All cases of glands, adenomas
      and carcinomas in pleomorphic adenomas have membranous and cytoplasmic
      immunostaining. Nuclear beta-catenin immunostaining was not observed. The
      antibody presented a fine granular arrangement in the cytoplasm and cellular
      membrane of duct and acinic cells. Higher beta-catenin index rates were seen
      mainly in salivary gland ducts and in ductal structures in the adenomas and
      carcinomas in pleomorphic adenomas. There was protein loss in pleomorphic
      adenomas and cytoplasmic accumulation in carcinoma in pleomorphic adenomas.
      CONCLUSIONS: The present study showed participation of the loss of beta-catenin
      adhesion molecule in the development of pleomorphic adenoma, and that the
      cytoplasmic accumulation of the molecule takes part in the malignant
      transformation of the pleomorphic adenoma into carcinoma in pleomorphic adenoma.

PMID- 16648763
TI  - Oral burning symptoms and burning mouth syndrome-significance of different
      variables in 150 patients.
AB  - OBJECTIVES: Despite the extensive amount of published literature upon burning
      symptoms in patients with clinically healthy appearance of the oral mucosa, as
      well as burning mouth syndrome (BMS) itself, they both remain still challenging
      topics. The aim of this study was to determine the real prevalence of "true" BMS
      in comparison to other patients with burning symptoms with clinically healthy
      appearance of the oral mucosa and then to compare "true" BMS patients with
      healthy controls regarding gastritis and intake of anxiolytics and angiotensin
      converting enzyme inhibitors. STUDY DESIGN: In 150 patients with burning symptoms
      of clinically healthy oral mucosa, local and systemic investigations were
      performed and they included detection of candidal infection, salivary flow rate,
      presence of oral galvanism and parafunctional habits as well as complete blood
      count, serum ferritin, serum glucose levels, serum antibodies to Helicobacter
      pylori together with detailed medical history with special regard to medication
      intake. After "true" BMS patients were identified they have been compared to the
      controls with regard to the presence of gastritis and the intake of anxiolytics
      and angiotensin converting enzyme inhibitors. RESULTS: Our results show that
      gastritis were significantly more present among "true" BMS patients and that they
      also significantly more intake anxiolitics, when compared to the control group.
      CONCLUSIONS: Our findings might lead to the conclusion that every "true" BMS
      patient should be referred to the gastroenterologist and psychiatrist.

PMID- 16648764
TI  - Dental caries in type 1 diabetics: influence of systemic factors of the disease
      upon the development of dental caries.
AB  - OBJECTIVES: Diabetes mellitus is one of the most common chronic diseases in the
      general population. A study is made of the presence of caries in type 1 diabetic
      patients. The specific aim was to determine whether such patients present a
      greater incidence of dental caries than non-diabetic individuals. An evaluation
      was also made of the relationship of caries to salivary flow and to factors
      inherent to the disease such as the degree of metabolic control, the duration of
      diabetes, and the existence of chronic complications. STUDY DESIGN: The study
      comprised 90 type 1 diabetics between 18 and 50 years of age, and a group of non
      diabetic controls matched for age and sex. Visual and tactile exploration of the
      dentition was carried out in all cases. Oral hygiene was rated based on the
      O'Leary plaque index, and basal (unstimulated) and stimulated salivary flow were
      evaluated in both groups. In the diabetic group, correlations were established
      with disease control based on the mean glycosylated hemoglobin (HbA1c) value
      corresponding to the two years prior to examination; evolution of the disease in
      years; and the existence of complications such as diabetic neuropathy or
      retinopathy. RESULTS: Under similar conditions of oral hygiene and salivary flow,
      the diabetic group showed a higher incidence of caries than the control group
      (p<0.05). Likewise, on specifically analyzing the diabetic group, metabolic
      control of the disease, the duration of diabetes, and the existence of
      complications of the disease exerted an influence upon the development of dental
      caries. CONCLUSIONS: Qualitative salivary studies are advised to better account
      for this increased incidence of caries in the diabetic population.

PMID- 16648765
TI  - Panoramic radiograph as a method for detecting calcified atheroma plaques. Review
      of literature.
AB  - Cerebrovascular accident (CVA) is the third cause of death in industrialized
      countries, following cardiovascular disease and cancer. It is therefore a
      significant public health issue, not only due to its high incidence, but also to
      the high costs involved in the physical and psychological rehabilitation of these
      patients. Dental Practitioners, as health care providers, ought to play their
      part in this issue and contribute, within their means, to the early detection of
      patients at risk of having a CVA. Since the eighties, different authors have
      described the possibility of detecting calcified atheroma plaques located at
      carotid artery bifurcation through panoramic radiograph. In this way, the Dental
      Practitioner s possibilities in this field have been extended. However, this new
      use of panoramic radiograph must overcome certain obstacles before it is
      implemented as a new screening method for patients at risk of having a CVA.
      Amongst these, we would have, on the one hand, the assessment of the real
      clinical significance, as regards prognosis, of atheroma plaque calcification as
      well as its usefulness as a factor for predicting the appearance of CVA symptoms
      and, on the other hand, the possibility of making a correct differential
      diagnosis regarding other calcified structures that may appear on panoramic
      radiograph.

PMID- 16648766
TI  - Analysis of the use of expansion osteotomes for the creation of implant beds.
      Technical contributions and review of the literature.
AB  - Sometimes, the severe superior maxillary atrophy compromises and even impide oral
      implants treatment. The use of rotatory instruments (drills) produce heat and
      lost of bone, but the osteotomes in implantology avoid this and simplifies the
      surgical treatment allowing implant installation with an easier technique. We
      present an expansive maxillary technique review, describing the main indications,
      advantages and disadvantages of this surgical procedure.

PMID- 16648767
TI  - Resonance frequency analysis after the placement of 133 dental implants.
AB  - INTRODUCTION: The primary stability of dental implants is related to the bone in
      contact with the latter, and can be evaluated by resonance frequency analysis.
      MATERIAL AND METHODS: Measurements were made in 133 implants (62 in the upper jaw
      and 71 in the mandible) of resonance frequency and insertion force to determine
      implant stability on the day of surgery, with an evaluation of its relationship
      to different variables. RESULTS: The stability quotient of the implants on the
      day of surgery was 62.1, with an insertion force of 35.7 N. The insertion force
      was proportional to the resonance frequency, with an increasing stability
      quotient with growing insertion force. The stability quotient was greater in the
      larger diameter implants, shorter implants, in mandibular placement and in areas
      of more compact bone. CONCLUSIONS: The stability quotient on the day of implant
      placement is greater in higher bone density areas.

PMID- 16648768
TI  - Stafne bone cavity: a retrospective study of 11 cases.
AB  - OBJECTIVE: To describe the clinical and radiological characteristics of patients
      with Stafne bone cavity. STUDY DESIGN: A retrospective, observational study of 11
      cases of Stafne bone cavity. After finding an imagine compatible with Stafne bone
      cavity in the Orthopantomograph(r) of 11 patients, a sialography of the
      mandibular gland was made in 3 cases, computerized tomography (CT) in 6 cases,
      and in 4 cases surgical intervention to confirm the diagnosis. RESULTS: The
      average age was 51.5 years, predominantly males. The entity was diagnosed
      incidentally during a routine radiology in all cases. The sialography revealed
      glandular tissue within the defect, and the CT demonstrated the conservation of
      the lingual cortical and the peripheral origin of the lesion. Glandular tissue
      was found within the lesions of two of the patients who underwent surgery, and in
      the other two the cavity was empty. No progressive changes were found in any of
      the 11 cases. CONCLUSIONS: Stafne bone cavity was an incidental finding,
      presenting no evolutionary changes, and as such conservatory therapy based on
      periodic controls was indicated. Currently, complementary techniques such as CT
      are sufficient to establish a certain diagnosis.

PMID- 16648769
TI  - Removal torque and physico-chemical characteristics of dental implants etched
      with hydrofluoric and nitric acid. An experimental study in Beagle dogs.
AB  - OBJECTIVE: To study the composition, surface characteristics and response to
      removal torque of an implant surface subjected to hydrofluoric acid etching and
      posterior passivating with hydrofluoric and nitric acid. STUDY DESIGN: Twelve
      implants were initially selected and their physico-chemical characteristics were
      evaluated by means of energy-dispersive X-rays (EDS), scanning electron
      microscopy (SEM) and photoelectron spectroscopy (XPS). In addition, 24 implants -
      12 measuring 8 mm and 12 measuring 10 mm in length - were implanted in 6 Beagle
      dogs. Twelve implants were removed after a recovery period of 6 weeks, followed
      by removal of the remaining 12 implants after 12 weeks, using a torque calibrator
      (Gauge Tonichi model BGT150CN-S) with a force registry range of 0-150 Ncm.
      RESULTS: EDS analysis of the surface chemical composition only revealed the
      presence of titanium in the etched surfaces. In the same way as with the surfaces
      of other dental implants, XPS analysis revealed traces of other elements present
      in the surface, fundamentally carbon. Following dual acid etching, the surface
      showed the roughness resulting from acid action, with a morphology that proved to
      be quite homogeneous. The roughness values obtained exceeded 1 mm. The mean
      removal torque values after 6 weeks were 79.7 Ncm for the 8 mm implants and 115
      Ncm for the 10 mm implants. After 12 weeks, these values increased to 101.2 Ncm
      and 139.7 Ncm, respectively. CONCLUSIONS: Hydrofluoric and nitric acid etching
      affords optimum surface characteristics comparable to those of other surfaces.
      The recorded removal torque values raise the possibility of human clinical
      application for early or immediate loading procedures.

PMID- 16648770
TI  - Osteochondroma of the coronoid process.
AB  - Osteochondroma is the most common benign neoplasia of the skeleton. In the head
      it was been described in cranial base, posterior maxillary surface, maxillary
      sinus, and different mandibular areas like condyle, ramus, body and symphysis.
      Osteochondroma of the coronoid process are rare. We present a review of the
      literature and the report of the cas of a 44 years old female patient presenting
      limited mouth opening and swelling of the left cheek, with diffuse limits, bony
      consistency, painless, and covered of normal skin. No temporomandibular joint
      disease was present. In panoramic radiographs was evident a coronoid tumor
      localized in the union of zigomatic arch and bone. Under general anaesthesia
      coronoidectomy was made, recovering mouth opening until 43 mm. The post-operative
      period was performed without complications. Histopatological examinations
      revealed normal trabecular bone covered with hyaline cartilage. The
      histopatological diagnosis was osteochondroma. Clinical and pathological aspects,
      treatment and differential diagnosis with other lesions are discussed.

PMID- 16648771
TI  - Antibiotic prophylaxis in Oral and Maxillofacial Surgery.
AB  - Antibiotic prophylaxis in oral and maxillofacial surgery aims the prevention of
      the infection of the surgical wound, either due to the characteristics of the
      surgery or the general state of the patient. This risk increases with the
      contamination of the surgical operation area, making it necessary to imply a
      prophylactic treatment of the infection in clean-contaminated and contaminated
      surgeries and treatment of the infection in dirty surgeries. Moreover, a proper
      surgical technique helps to reduce the development of the postsurgical infection.
      The elective antibiotic chemotherapy ranges from penicillin-derivates with
      betalactamase inhibitors (amoxycillin-clavulanate, ampicilin-sulbactam) to second
      or third generation cephalosporins, quinolones or clindamycin. The indication for
      the use of these antibiotics depends on the type of surgery in oral and
      maxillofacial surgery, according to the degree of contamination. Thus in oral
      surgery and surgery of the salivary glands the literature demonstrates that there
      is not a better prognosis when using prophylactic antibiotherapy instead of not
      using it in healthy patients. In traumatology this prophylaxis is justified in
      compound fractures and those communicating with paranasal sinuses. En orthognatic
      surgery there is disagreement according to the criteria of using antibiotic
      prophylaxis, but short term treatment is preferred in case of using it. In
      oncological surgery it has been demonstrated the reduce in incidence of
      postsurgical infection using prophylactic peroperative antibiotherapy, mostly in
      those cases in which oral mucosa and cervical area contact.

PMID- 16648772
TI  - Choice of ceramic for use in treatments with porcelain laminate veneers.
AB  - Porcelain laminate veneers (PLVs) have been used for over two decades to treat
      esthetic and/or functional problems, particularly in the anterior sector. A range
      of dental ceramic materials are presently available on the market for these
      treatments, though with very different characteristics in terms of the
      composition, optic properties and manufacturing processes involved. As a result,
      selection of the material best suited for the management of each individual
      patient may prove complicated. The present study proposes a simple system for
      selecting the most appropriate ceramic material, based on the two variables that
      most influence the esthetic outcome: the intrinsic characteristics of the
      substrate tooth, and the characteristics of the ceramic material in terms of
      resistance and optic properties.

PMID- 16648773
TI  - The evaluation of ghrelin mRNA expression in human somatotroph adenomas.
AB  - Ghrelin is one of the peptides involved into GH-release, binding to specific GHS
      receptors on hypothalamus and pituitary. The ghrelin peptide and ghrelin mRNA
      have been detected in several regions of hypothalamus, in normal pituitary, as
      well as in various types of pituitary adenoma, with different levels of
      expression in different tumour types. We decided to determine the expression of
      ghrelin in somatotroph adenomas. Human pituitary somatotroph adenoma tissues were
      obtained at the time of transsphenoidal surgery from 3 acromegalic patients and
      studied for ghrelin mRNA expression. Before surgery each patient received a
      somatostatin analogue treatment at doses 20 mg, 30 mg, 30 mg at 30 days
      intervals. 20 mg of each tissue sample was used for the isolation of total
      cellular RNA. The reverse transcription and real-time PCR were performed
      according to Korbonits et al. method. The reverse transcription of total RNA to
      cDNA was performed using Super Script TM Rnase H RT kit according to manufacturer
      protocol. We wished to determine the number of copies of ghrelin gene within the
      single cell. We used the beta-actin, and the GAPDH genes as a reference molecules
      for standard curve calculation. Ghrelin mRNA was not detected in any examined
      tissues. We postulate that the absence of the ghrelin gene transcript is mainly
      due to the treatment with somatostatin analogues administered preoperatively,
      which could have suppressed the ghrelin gene transcription.

PMID- 16648774
TI  - The effect of cocaine-amphetamine regulated transcript (CART) on the activation
      of the pituitary-adrenal axis.
AB  - OBJECTIVE: It has been reported that the cocaine and amphetamine regulated
      transcript (CART) is widely expressed in the hypothalamic nuclei involved in the
      mechanism of hormonal secretion. RESEARCH METHODS: In order to evaluate the
      effect of CART on the activation of the pituitary-adrenal axis in the rat, CART
      (55-102) in a dose of 0.5 microg in 5 microl CSF was infused into the third
      ventricle (icv) with an automatic pump. At 10, 30, 60, 120 min after the infusion
      of CART or vehicle, the animals were decapitated and the trunk blood was
      collected. Serum ACTH and corticosterone concentrations were measured with RIA
      kits provided by Phoenix Pharmaceuticals and ICN Biomedicals USA, respectively.
      RESULTS: The stimulating effect of CART on ACTH concentration was observed only
      30 min after icv injection. However, CART stimulated corticosterone release at
      10, 30, 60 min after icv injection. CONCLUSIONS: CART (55-102) administered
      intracerebroventricularly (icv) stimulated ACTH and corticosterone release. The
      stimulating effect of CART on ACTH was short-lived.

PMID- 16648775
TI  - The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for
      negative symptoms in schizophrenia: negative results.
AB  - The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over
      the prefrontal cortex is a promising method for the treatment of negative
      symptoms of schizophrenia. Using double-blind sham-controlled parallel design, we
      evaluated the effect of HF-rTMS over the left dorsolateral prefrontal cortex
      (DLPFC) on negative symptoms in patients with schizophrenia. Sixteen
      schizophrenia patients with predominantly negative symptoms on stable
      antipsychotic medication were treated with 20 Hz rTMS (90% of motor threshold,
      2000 stimuli per session) over ten days within 2 weeks with six weeks follow-up.
      The effect was assessed using PANSS, CGI, MADRS and neuropsychological tests. We
      failed to find any significant effect of active rTMS. Sham rTMS showed a trend
      for improvement over time on positive and negative subscales of PANSS and MADRS.
      Between-group comparisons failed to reveal any significant differences on any
      rating scales except a positive subscale of PANSS after 8 weeks. Results from our
      study did not confirm that HF-rTMS over the left DLPCF affects the negative
      symptoms of schizophrenia and alternative rTMS approaches are discussed.

PMID- 16648776
TI  - The changes of hormonal serum levels and ovulation/pregnancy rates after ovarian
      electrocautery in microlaparoscopy and laparoscopy in patients with PCOS.
AB  - OBJECTIVES: To compare the efficacy of ovarian electrocautery performed during
      microlaparoscopy and laparoscopy, basing on ovulation and pregnancy rates
      obtained within one year of follow-up. MATERIALS AND METHODS: Ovarian drillings,
      performed with the use of endoscopic methods, were carried out in 135 women with
      hormonal and ultrasound features of PCOS, aged 30-39 (average age 36 +/- 3.3).
      Laparoscopic ovarian electrocautery was carried out in 65 cases, whereas
      microlaparoscopic drilling was conducted in 70 cases. The obtained results were
      compared in regard to duration of the procedure and ovulation/pregnancy rates
      within one year of follow-up. Changes in hormonal profiles were also compared in
      both groups, measured in patients who did not get pregnant before, and 3 months
      after, the procedures. RESULTS: The difference in durations between the two
      studied procedures was statistically significant (19 +/- 3 min vs. 24 +/- 4.4
      min; p<0.001). However, the ovulation and pregnancy rates did not differ
      significantly between the two groups (72% vs. 77.7%; p<0.5 and 19.4% vs. 20%;
      p<0.95, respectively). There were also similar trends in hormonal changes after
      microlaparoscopic and laparoscopic drilling. CONCLUSIONS: The efficacy of ovarian
      drilling in PCOS, estimated by ovulation and pregnancy rates within 12 months of
      follow-up is similar for microlaparoscopy and laparoscopy, as well as the trends
      in hormonal changes. Ovarian electrocautery is significantly longer in
      microlaparoscopy, but the difference in time is of no practical impact.

PMID- 16648777
TI  - The association between high-activity COMT allele and alcoholism.
AB  - OBJECTIVES: The catechol-O-methyltransferase (COMT) is an enzyme involved in the
      metabolism of dopamine, adrenaline and noradrenaline. The Val158Met polymorphism
      of the COMT gene has been previously associated with a variability of the COMT
      activity, and alcoholism. The aim of the present association study was to examine
      the relationship between the Val158Met polymorphism of the COMT gene and
      dispositions to alcoholism. METHODS: In our case control study we analyzed DNA
      samples from 799 subjects in total (279 male alcoholics and 120 female
      alcoholics, 151 male controls and 249 female controls). The restriction analysis
      for the detection of the Val158Met polymorphism was used. RESULTS: We found a
      relationship between the Val158Met polymorphism of the COMT gene and alcoholism
      in male subjects. We found the significant difference between male alcoholics and
      male controls in allele and genotype frequencies (p<0,007; and p<0,04
      respectively). CONCLUSIONS: Our study confirmed the relationship between the COMT
      polymorphism and alcoholism in the Czech male population.

PMID- 16648778
TI  - The effects of Levosimendan on global haemodynamics in patients with cardiogenic
      shock.
AB  - Levosimendan may improve the outcome of acute heart failure patients with
      preserved arterial blood pressure. However, the data on its use in critically ill
      patients are scarce. OBJECTIVES: The aim of this study was to assess the effects
      of levosimendan on global haemodynamics in patients with cardiogenic shock.
      MATERIALS AND METHODS: Fourteen adult patients in cardiogenic shock were studied
      prospectively. One patient died after 10 hours and was excluded from final
      analysis. Haemodynamic monitoring included arterial and pulmonary arterial
      thermodilution catheters. Before levosimendan administration, 12 patients
      required norepinephrine, 6 patients dobutamine and 4 patients intraaortic balloon
      pump. Levosimendan was given as a bolus (12 microg x kg(-1) x 10 min(-1))
      followed by 24 hrs infusion (0.1 microg x kg(-1) x min(-1)). Baseline data had
      been collected before levosimendan administration. Following data sets were
      obtained after 1, 8, 16 and 24 hours. Positive haemodynamic response was defined
      as an increase of > or = 30% in cardiac output. RESULTS: Eleven patients met the
      criterion for the positive haemodynamic response. During levosimendan infusion
      systemic vascular resistance decreased (p<0.05) whereas cardiac output (p<0,001)
      and urine output increased (p<0.01). Mean arterial pressure and heart rate
      remained unchanged. No severe arrhythmias occurred and norepinephrine-dose did
      not change. Two patients were classified as non-responders. CONCLUSIONS: Our
      results suggest that levosimendan infusion given as adjunctive therapy in
      patients with cardiogenic shock may be safe with beneficial effects on global
      haemodynamics.

PMID- 16648779
TI  - Solitary epileptic seizure--the risk of recurrence.
AB  - Patients experiencing solitary unprovoked epileptic seizure have different risks
      of recurrence. The possible risk factors include in particular: structural
      cerebral lesion and its cause, history of febrile seizures, family history of
      epilepsy, the type of seizure, epileptiform EEG discharges and the problem of
      initiation or (or not initiation) of antiepileptic treatment after the first
      paroxysm. The factors shown above were evaluated in a group of 30 patients with
      solitary unprovoked epileptic seizure. Regarding recurrence of epileptic seizure,
      the only significant factor appeared to be initiation of treatment after the
      first unprovoked paroxysm (p<0.001). We observed a 30% and 33.33% risk of
      recurrence following the initial epileptic seizure in patients after the first
      unprovoked seizure in less than 1 and 3 years, respectively.

PMID- 16648780
TI  - Reappearance of catatonia. A case report.
AB  - We describe a patient who was ill for more than 15 years. She was treated
      predominantly as a neurological case because of multiple motor signs. The
      diagnosis of catatonia was considered at the time when she was hospitalized in a
      psychiatric hospital after a suicidal attempt. The "therapeutic blindness", which
      was obviously present during 15 years of her illness, is discussed: the ICD--10
      is perhaps misleading regarding this diagnosis while it associates it too tightly
      only to schizophrenia.

PMID- 16648781
TI  - Rapid Ca(2+) signaling induced by Bisphenol A in cultured rat hippocampal
      neurons.
AB  - OBJECTIVES: Bisphenol A (BPA) is a typical endocrine disrupter. We investigated
      the mechanisms of rapid Ca(2+) signaling induced by a low dose BPA application in
      cultured hippocampal neurons. MATERIALS AND METHODS: The primary culture of
      hippocampal neurons were prepared from postnatal 3 to 5-day-old rats. Cells were
      loaded with Calcium Green-1 fluorophore. Ca(2+) imaging and analysis were
      performed by Argus system. RESULTS: The application of BPA at 10-100 nM induced a
      transient increase in the intracellular Ca(2+) of N-methyl-D-aspartate (NMDA)
      responsive neurons. The Ca(2+) transient occurred within 30 sec after the BPA
      application. The proportion of BPA-responsive neurons was 9.6 % and 8.5 % of the
      total NMDA-responsive neurons, respectively, upon 10 nM and 100 nM BPA
      application. The pre-treatment of neurons with Ca(2+) channel blockers,
      thapsigargin and nifedipine, considerably decreased the proportion of BPA
      responsive neurons to 0.7 % and 3.7%, respectively. The treatment of neurons with
      an antagonist of estrogen receptor, ICI 182,780, also significantly decreased the
      proportion of BPA-responsive neurons down to 1.1 %. CONCLUSION: These results
      suggest that a low dose BPA application rapidly drives the Ca(2+) signaling
      system via activation of non-genomic pathway including estrogen receptors.

PMID- 16648782
TI  - Prolonged use of phenytoin, carbamazepine or valproate monotherapy on plasma
      levels of folate and B(12): a comparison between epileptic patients with or
      without cardiovascular disorders.
AB  - PURPOSE: Previous studies showed an association between the blood levels of
      folate and vitamin B(12) and the risk for cardiovascular disease. The aim of this
      study is to investigate the effect of chronic use of phenytoin, carbamazepine or
      valproate monotherapy on the plasma levels of folate and B(12), and to compare
      folate and B(12) levels in epileptic patients with or without cardiovasular
      disorders. METHODS: The study was conducted in the outpatient neurology clinic at
      Bahrain Defence Force (BDF) Hospital between January-July, 2005. Medical
      information was obtained by interviewing the patients and examining their
      hospital records. Blood folate and vitamin B(12) were measured by Immulite
      immunoanalysis assay using chemoluminescence. RESULTS: A total of 26 consecutive
      outpatients (17 males, 9 females) were recruited in the study. Their mean age +/-
      SD was 38.2 +/- 20.1 year (range 15-77 year). Five (19.2%) had complex partial
      epilepsy and the remainder had tonic-clonic seizures. They had epilepsy for 15.7
      +/- 8.1 years (range 2-35 years). Thirteen of them used phenytoin, nine
      carbamazepine and four used valproate. The duration of the treatment (years),
      dose (mg/day) and serum concentration (micromol/l) were 18.3 +/- 10.6, 376.9 +/-
      180.4, 41.6 +/- 25.6, for phenytoin, 14.5 +/- 11.7, 422.2 +/- 175.0, 31.1 +/-
      15.9 for carbamazepine and 18.3 +/- 6.3, 400, 567.7 +/- 78.1 for valproate,
      respectively. Eleven (42.3%) had established cardiovascular disorders such as
      hypertension, myocardial infarction or stroke. The mean level of plasma folate
      (12.94 +/- 6.76 ng/ml) and B12 (484.94 +/- 191.25 pg/ml) in epileptic patients
      with cardiovascular disorders compared to their values (11.27 +/- 5.84), (514.49
      +/- 225.31) respectively in epileptics with no cardiovascular disorders were not
      statistically significant in the two groups. CONCLUSION: In epileptic patients on
      chronic therapy with phenytoin, carbamazepine or valproate folate and B(12)
      levels were not different in patients with or without cardiovascular disorders.

PMID- 16648783
TI  - Premature fusion and excessive calcification of coronal sutures in patients with
      Klinefelter syndrome.
AB  - OBJECTIVE: The purpose of this paper is to report on radiographic features of the
      cranial vault abnormalities frequently seen but not yet described in detail in
      patients with Klinefelter syndrome. SUBJECTS: Our studies comprised 72 patients
      with Klinefelter syndrome and 47,XXY karyotype. The majority of the patients were
      young between the ages of 16 to 28 years. METHODS: Plain skull radiographs were
      taken in the frontal and lateral projections. RESULTS: Several abnormalities were
      observed on skull radiographs of the Klinefelter patients. The most frequent was
      a premature fusion of the coronal sutures that occurred in 54 of 62 younger
      patients. In 42 cases extensive calcifications of these sutures were observed.
      The calcified sutures were dense and widened. In 24 patients the inner table in
      the anterior part or the parietal bone displayed a marked disruption with
      thinning of the calvaria at this place. In the posterior part of the parietal
      bone in 21 patients the inner table was thickened and excessively dense. On
      frontal radiographs, in 30 patients, there was a flattening of the squamous part
      of the temporal bones. CONCLUSIONS: Skull radiographs in Klinefelter patients
      frequently display abnormalities: premature fusion and excessive calcifications
      of the coronal sutures, irregularities of the inner table of the parietal bone,
      and flattening of the temporal bones. These radiographic features, when present,
      may draw attention to the XXY syndrome as the underlying cause of the
      abnormalities.

PMID- 16648784
TI  - Polymorphism of DRD2 gene and ADHD.
AB  - OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a prevalent
      childhood disorder. Evidence from the family and twin studies suggest that ADHD
      is familiar and highly heritable. Association studies are frequently used for the
      searching of markers responsible for genetic basis of ADHD. We investigated TaqI
      polymorphism of the dopamine receptor D2 (DRD2) in relationship with ADHD. The
      association between TaqI A polymorphism of DRD2 gene and ADHD has previously been
      published. DESIGN: We used the association study to test the relationship between
      TaqI A polymorphism of DRD2 gene and ADHD on groups of ADHD boys and control
      boys. SETTING: For DNA isolation, buccal tissue was used. PCR with restriction
      analysis of PCR products was used for genotyping. RESULTS: We found statistically
      different genotypic and allelic frequencies (p < 0.008, p < 0.002, respectively)
      of DRD2 polymorphism between two studied groups of boys. MAIN FINDINGS: According
      to our results we suppose that polymorphism TaqI A of DRD2 gene is involved in
      the pathogenesis of childhood ADHD in male subjects. Allele A1 and genotype A1A1
      in male subjects is associated with ADHD. CONCLUSIONS: Our study confirmed the
      relationship between TaqI A polymorphism of DRD2 gene and ADHD published
      previously.

PMID- 16648785
TI  - Photodynamic therapy with verteporfin in subfoveal amelanotic choroidal melanoma
      (A controlled case).
AB  - A 57-year old man with 2.7 mm thick subfoveal amelanotic choroidal melanoma of
      the right eye was indicated for photodynamic therapy with verteporfin. The tumor
      fully disappeared 1 month after the treatment, the visual acuity improved from
      4/16 to 4/4. The disease did not recur during 24-month follow-up.

PMID- 16648786
TI  - Permanent effects of postnatal administration of beta-adrenergic ligands on the
      volume of sexually dimorphic nucleus of the preoptic area (SDN-POA) in rats.
AB  - BACKGROUND: beta-adrenergic ligands have been shown to influence sexual
      differentiation of the brain. In the present study we document that short
      postnatal treatment with beta-adrenergic agonists or antagonists may permanently
      reverse the morphological sex of the brain, as judged by the volume of sexually
      dimorphic nucleus of the preoptic area (SDN-POA). Female rats treated by beta(2)
      adrenergic stimulating ligands exhibit an increased, male type SDN-POA volume
      while male rats treated by beta1-adrenergic antagonists show a decreased, female
      type of SDN-POA volume. OBJECTIVES: To analyze the volume of SDN-POA of adult
      rats after postnatal administration of betaadrenergic ligands. METHODS: From the
      second day of life, over 5 consecutive days, all the neonates were injected
      subcutaneously with the following drugs: isoproterenol, salbutamol, metoprolol
      alprenolol or saline. SDN-POA volumes were estimated planimetrically on serial
      brain slides. RESULTS: In male rats the mean volume of SDN-POA was 9.97 +/- 1.66
      x 10(-3) mm(3), in female rats the respective volume reached 4.02 +/- 1.26 x 10(
      3) mm(3) only and was 2.5 times lower, the difference being highly statistically
      significant. Postnatal administration of isoproterenol remained without effect in
      male rats but diminished the SDN-POA volume in female rats, thus increasing the
      sexual dimorphism. The disappearance of sexual dimorphism was noted in rats
      treated postnatally with salbutamol. This effect was due to the increase in SDN
      POA volumes in female rats, up to 9.81 +/- 2.64 x 10(-3) mm(3), the levels
      approaching the male type of POA differentiation. Postnatal alprenolol treatment
      influenced the sexual dimorphism of the brain by decreasing the SDN-POA volume
      reached by adult males. In fact, in rats treated postnatally with alprenolol, the
      volume of the nucleus reached only 4,44 +/- 1,61 x 10(-3) mm(3), being not
      statistically different from female nuclei. The effect of metoprolol pretreatment
      was similar to alprenolol. Male volumes of SDN-POA were restored both by
      isoproterenol and salbutamol in metoprolol pretreated rats and by isoproterenol
      only in alprenolol treated rats. CONCLUSION: It appears that inhibition of
      beta(1)-adrenergic pathway is able to shut off the physiologic mechanisms of male
      differentiation of SDN-POA, and the subsequent beta(2)-adrenergic stimulation
      activates an alternative mechanism of masculinization. beta(2)-adrenergic signal
      is able to masculinize rat preoptic area in females as well. From the presented
      data it may be concluded that beta adrenoreceptors participate in sexual
      differentiation of preoptic area in rats and the modulation of their activity in
      postnatal period permanently influences the morphology of the sexually
      differentiated nucleus of the preoptic area.

PMID- 16648787
TI  - Parentally-adjusted deficit of height as a prognostic factor of the effectiveness
      of growth hormone (GH) therapy in children with GH deficiency.
AB  - INTRODUCTION: Parental height is the most important identifiable factor
      influencing final height (FH) of children with growth hormone (GH) deficiency
      (GHD), treated with GH. AIM: Assessment of FH of patients with GHD--classified
      into familial short stature (FSS) and non-familial short stature (non-FSS)
      according to parentally adjusted deficit of height. PATIENTS AND METHODS: The
      analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height
      was compared with patients' height before GH therapy, predicted adult height
      (PAH) and target height (TH). RESULTS: Both GH peak in stimulating tests and
      height standard deviation score (SDS) before the therapy were significantly lower
      in non-FSS than in FSS. Target height was significantly lower in FSS than in non
      FSS. Parentally-adjusted deficit of height was significantly more profound in non
      FSS than in FSS. The prognosis of adult height was very similar in both groups of
      patients, being significantly worse in non-FSS than in FSS while corrected by TH.
      The absolute FH was similar in FSS and non-FSS, being, however, significantly
      lower in non-FSS than in FSS while corrected by TH. Improvement of height was
      significantly better in non-FSS than in FSS. In both groups, FH SDS was
      significantly better than height SDS before the therapy (H0SDS). In FSS group,
      PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS
      group FH was significantly higher than PAH, but both FH and PAH were
      significantly lower than TH. CONCLUSIONS: 1) Growth hormone therapy was more
      effective in the patients with non-FSS than in those with FSS. 2) Parentally
      adjusted deficit of height is an important prognostic factor of GH therapy
      effectiveness.

PMID- 16648788
TI  - Microdialysis measurement of acetylcholine in rat hippocampus during severe
      insulin-induced hypoglycemia.
AB  - OBJECTIVE: It has been well acknowledged that hypoglycemia induces cognitive
      impairment. However, the behavior of hippocampal cholinergic system, which is
      thought to play a key role in cognition, during hypoglycemia remains to be
      elucidated. MATERIALS AND METHODS: In this study we conducted a microdialysis
      using 9 weeks old virgin male Wistar/ST rats to determine the changes of
      extracelluar acethylcholine and glucose levels in the hippocampus during insulin
      induced severe hypoglycemia, and compared the results with those obtained from a
      microdialysis in the striatum. RESULTS: The extracelluar concentrations of
      acethylcholine both in the hippocampus and striatum did not change during
      hypoglycemia. CONCLUSION: The results of the present study may suggest that
      changes of hippocampal cholinergic release may not be involved in the mechanism
      of cognitive impairment during hypoglycemia.

PMID- 16648789
TI  - The effect of exhaustion exercise on thyroid hormones and testosterone levels of
      elite athletes receiving oral zinc.
AB  - OBJECTIVES: The present study aims to investigate how exhaustion exercise affects
      thyroid hormones and testosterone levels in elite athletes who are supplemented
      with oral zinc sulfate for 4 weeks. METHODS: The study included 10 male
      wrestlers, who had been licensed wrestlers for at least 6 years. Mean age of the
      wrestlers who volunteered in the study was 18.70 +/- 2.4 years. All subjects were
      supplemented with oral zinc sulfate (3 mg/kg/day) for 4 weeks in addition to
      their normal diet. Thyroid hormone and testosterone levels of all subjects were
      determined as resting and exhaustion before and after zinc supplementation.
      RESULTS: Resting TT3, TT4, FT3, FT4 and TSH levels of subjects were higher than
      the parameters measured after exhaustion exercise before zinc supplementation
      (p<0.05). Both resting and exhaustion TT3, TT4 and FT3 values after 4-week zinc
      supplementation were found significantly higher than both of the parameters
      (resting and exhaustion) measured before zinc supplementation (p<0.05). Resting
      total testosterone and free testosterone levels before zinc supplementation were
      significantly higher than exhaustion levels before zinc supplementation (p<0.05).
      Both resting and exhaustion total and free testosterone levels following 4-week
      zinc supplementation were found significantly higher than the levels (both
      resting and exhaustion) measured before zinc supplementation (p<0.05).
      CONCLUSION: Findings of our study demonstrate that exhaustion exercise led to a
      significant inhibition of both thyroid hormones and testosterone concentrations,
      but that 4-week zinc supplementation prevented this inhibition in wrestlers. In
      conclusion, physiological doses of zinc administration may benefit performance.

PMID- 16648790
TI  - Zinc supplementation in rats subjected to acute swimming exercise: Its effect on
      testosterone levels and relation with lactate.
AB  - OBJECTIVE: There is fairly scarce information about the effects of zinc, an
      essential trace element, on performance. Studies concerned with the relation
      between zinc and exercise mostly concentrate on the distribution of this element
      in the body in response to exercise. The objective of the present study is to
      explore how zinc supplementation affects testosterone levels and its relation
      with lactate in rats subjected to acute swimming exercise. MATERIALS AND METHODS:
      Thirty adult male rats of Sprague-Dawley species were equally allocated to 3
      groups. Group 1: Control. Group 2: Group subjected to 30-minute acute swimming
      exercise. Group 3: Group supplemented with intraperitoneal (i.p.) zinc (3 mg/kg
      day) for 4 weeks and subjected to 30-minute swimming exercise. Blood samples
      collected from all experimental animals by decapitation method were analyzed to
      determine free and total testosterone and lactate levels in the plasma. RESULTS:
      Group 3 had the highest free and total testosterone levels, followed by Group 1
      and Group 2. The highest lactate levels were found in Group 2 and the levels in
      Group 3 were higher than those in Group 1. CONCLUSION: Results of the study
      demonstrate that zinc supplementation leads to a significant increase in
      testosterone levels and a significant decrease in lactate levels. In conclusion,
      physiological doses of zinc supplementation can be useful for performance.

PMID- 16648791
TI  - Metal-specific lymphocyte reactivity is downregulated after dental metal
      replacement.
AB  - OBJECTIVES: This study was done to evaluate the results and clinical relevance of
      an optimized lymphocyte proliferation test, MELISA, for metal-induced
      inflammation in patients with CFS-like symptoms. The treatment of patients
      consisted of the replacement of incompatible dental materials (RID) together with
      supportive anti-oxidant therapy. DESIGN OF THE STUDY: 513 patients were tested by
      MELISA at the beginning of the study. Out of this group, 248 patients were
      available for follow-up MELISA after RID. METHODS: In MELISA, lymphocytes are
      isolated from the blood and cultivated with different metal salts in tissue
      culture medium containing 10% inactivated human AB+ serum or autologous serum.
      After 5 days, the presence of metal-reactive lymphocytes are measured by isotope
      labelling of newly formed DNA in growing lymphoblasts and evaluated by
      calculating the Stimulation Index. RESULTS: Nickel was the most common
      sensitizer, followed by inorganic mercury, thimerosal, lead, cadmium, palladium
      and gold. After RID treatment, a decrease of metal-specific lymphocyte responses
      in patients who reacted to metals at the beginning of the study could be
      observed. The cultivation of lymphocytes in autologous and homologous serum did
      not significantly affect the results. Simultaneous, the health status of patients
      improved as well. CONCLUSIONS: Replacement of incompatible dental materials
      resulted in down-regulation of metal-induced lymphocyte sensitivity in vitro, as
      well as in the improvement of health status of majority of patients with
      unspecific CFS-like symptoms.

PMID- 16648792
TI  - Metabolic stroke in three years old boy as the consequence of metabolic
      derangement. A case report of recidiving Reye's-like syndrome.
AB  - Three years old boy with developmental renal dysplasia was hit as newborn child
      by attack of cerebral edema with metabolic disturbances (hypoglycemia,
      hypophosphatemia, ketoacidosis and with hypocoagulation state) and was classified
      as child at risk in the pediatric evidence. In the third year of the age he went
      through nephrectomy and after the operation, the similar metabolic disturbances
      occurred (hypoglycemia, ketoacidosis, derangement of the metabolic situation).
      Cerebral edema and the metabolic stroke developed. Reye's-like syndrome was
      considered and serious functional disturbances of basal ganglia and brain-stem
      structure were observed.

PMID- 16648793
TI  - Menstrual cycle and sex hormone profile in kidney-transplanted women.
AB  - OBJECTIVES: End-stage renal failure is associated with amenorrhaea and extremely
      reduced fertility. After successful kidney transplantation restoration of
      menstrual function is observed. The aim of the study was to investigate ovarian
      function and menstrual cycles in kidney-transplanted women of reproductive age.
      MATERIALS AND METHODS: 55 ovarian cycles in kidney transplanted women, aged 18-40
      years, being one to five years after transplantation, were analyzed and compared
      with 50 cycles of healthy women. The duration of the cycles as well as FSH, LH,
      estradiol, progesterone, prolactin and testosterone serum concentrations were
      monitored. Simultaneously the presence of ovulation was evaluated with repeated
      sonographic examinations. RESULTS: Regular menstrual cycles were observed in
      72.7% of kidney transplanted women. The rates of ovulatory cycles were similar in
      the study group and the control: 65% and 70% respectively. Mean estradiol level
      in the follicular phase of the cycle was significantly higher in transplant
      patients (205.9, SD 160.22 vs 135.9 pg/ml, SD 68.34 in the control).
      Significantly lower levels of progesterone (13.2 ng/ml, SD 14.2 vs 26.7 ng/ml, SD
      14.1 in the control) and testosterone were observed in kidney recipients. Other
      hormonal parameters did not differ significantly between the groups. CONCLUSIONS:
      The rate of ovulatory cycles in regularly menstruated kidney transplanted
      patients is similar to that of healthy women. Similar serum FSH, LH and PRL
      concentrations as well as increased levels of estrogens are observed in kidney
      graft recipients in comparison to healthy non-recipients. Increased levels of
      estrogens put that group of patients at risk of gynecological pathologies.

PMID- 16648794
TI  - Melatonin supplementation to rats subjected to acute swimming exercise: Its
      effect on plasma lactate levels and relation with zinc.
AB  - OBJECTIVE: The objective of the present study is to examine the effect on
      melatonin supplementation on plasma lactate levels and its relation with zinc in
      rats subjected to acute swimming exercise. METHODS: Thirty adult male rats of
      Spraque-Dawley species were allocated to 3 groups, each containing an equal
      number of rats: general control group which was not subjected to any procedure
      (Group 1), the group which was subjected to 30 minutes acute swimming exercise
      (Group 2), and the group which was subjected to 30 minutes acute swimming
      exercise after 4-week intraperitoneal (i.p.) melatonin (3 mg/kg/day)
      supplementation. Lactate and zinc levels in the plasma were studied in the blood
      samples taken from the experimental animals by decapitation method. RESULTS: The
      animals in the control group, which was not subjected to any procedure (group 1),
      had higher lactate levels than those in groups 2 and 3 (p<0,05). Lactate levels
      in the swimming group supplemented with melatonin (group 3) were lower than those
      in group 2 (swimming group) (p<0,05). The highest plasma zinc levels were
      obtained in the melatonin-supplemented swimming group (group 3) (p<0,05). Group 2
      (swimming control) had the lowest plasma zinc levels (p<0,05). CONCLUSION:
      Results of the study demonstrate that melatonin supplementation to rats subjected
      to acute swimming exercise reduces lactate levels, thereby delaying exhaustion.
      Increased zinc levels may be mediating this melatonin effect.

PMID- 16648795
TI  - Involvement of cannabinoid CB1 and CB2 receptor activity in the development of
      behavioural sensitization to methamphetamine effects in mice.
AB  - OBJECTIVES: An increased behavioural response ("behavioural sensitization") to
      drugs of abuse occurs after repeated treatment. In the present study the
      possibility of cross-sensitization existence between various cannabinoid receptor
      ligands--CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM
      251 with methamphetamine was explored. METHODS: Locomotion in the open field was
      measured in naive mice and in those pre-treated acutely and repeatedly (for 8
      days), respectively, with either vehicle or tested drugs. RESULTS:
      Methamphetamine produced significant sensitization to its stimulatory effect on
      locomotion. Methanandamide pre-treatment elicited cross-sensitization to
      methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre
      treatment with methamphetamine+AM 251 suppressed sensitization to
      methamphetamine. CONCLUSIONS: These results suggest that the activity of the
      endocannabinoid system is involved in the neuronal circuitry underlying the
      development of sensitization to methamphetamine.

PMID- 16648796
TI  - Influence of perineal swellings on behavior and stress reaction in levonorgestrel
      implanted Macaca sylvanus females.
AB  - OBJECTIVES: Contraceptives are common tools in controlling the reproductive
      physiology in primates. Levonorgestrel, a synthetic gestagen, can usually enable
      contraception and does not suppress the extension of perineal swellings. SETTING:
      This study investigated the effects on intra-sexual behavior and fecal cortisol
      excretion rates in different swollen Barbary macaque females (N =24) during the
      non-reproductive phase of the year. The study was conducted on a semi-free
      population at Affenberg Salem (Germany). RESULTS: The results showed that females
      with reduced swellings received more aggressive encounters than females with
      enlarged perinea; whereas, at the same time the latter individuals have increased
      their active grooming interactions paralleled with decreased fecal cortisol
      excretion rates. No correlations were found between the perineal swelling size
      and the dominance rank, age, or implantation time of the females. MAIN FINDINGS:
      This report shows that the rate of perineal swelling expression can modulate
      intra-sexual behavior and stress reactivity in levonorgestrel implanted Barbary
      macaque females. CONCLUSION: We conclude that large perineal swellings represent
      an influencing key factor in Barbary macaque females' social interactions,
      irrespective of whether these signals are shown naturally or induced
      biochemically.

PMID- 16648797
TI  - Increased lipid peroxidation in growth hormone-deficient adult patients.
AB  - OBJECTIVES: Growth hormone (GH) deficiency in adults is associated with a higher
      risk of atherosclerosis and cardiovascular disease. It has recently been
      suggested that enhanced oxidative stress may be implicated in vascular (and
      probably other) disturbances, occurring in GH-deficient subjects. The aim of the
      study was to evaluate serum levels of lipid peroxidation (LPO) products in adult
      patients with severe GH deficiency during insulin tolerance test (ITT), and to
      estimate the relationships between LPO and GH, total cholesterol, low-density
      lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and other
      parameters of metabolic processes. MATERIAL AND METHODS: Twelve adult patients
      with severe GH deficiency hospitalized in our department and 12 healthy
      volunteers, matched for sex, age and body mass index (BMI), were enrolled in the
      study. Peripheral blood was collected during ITT. The concentrations of
      malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of LPO, were
      measured in blood serum. RESULTS: Serum LPO level was approximately twice as high
      in GH-deficient patients as in the controls at each time point of ITT. A positive
      correlation was found between bone mineral density in the lumbar spine and GH
      concentration in GH-deficient patients. A positive correlation was found between
      LPO and BMI in the controls, but no such correlation was observed in GH-deficient
      patients. CONCLUSION: The increased LPO in GH-deficient patients may indicate
      enhanced oxidative stress within the vascular compartment and, possibly, in other
      tissues, which may contribute to the proatherogenic state and corresponding organ
      disturbances in GH-deficient patients, independently from conventional risk
      factors.

PMID- 16648798
TI  - Effects of melatonin on the process of apoptosis in rat thyroid follicular cells.
AB  - OBJECTIVES: Apoptosis, or programmed cell death, is a normal component in the
      development of multicellular organisms and is essential for many physiological
      processes. Apoptosis is a process in which cells play an active role in their own
      death (apoptosis is often referred to as "cell suicide"). Disturbances of
      apoptosis regulation can result in many diseases. Certain substances (for example
      -aflatoxin B1; AFB1) can induce apoptosis in various organs and tissues.
      Melatonin (Mel) is a hormone (indoleamine) which has antioxidant,
      antiproliferative and, potentially, anticancerogenic activities. The aim of our
      study was to examine the influence of late-afternoon (1600-1800) intraperitoneal
      (i.p.) Mel injections, administered for 3 weeks, on the process of apoptosis in
      male Wistar rat thyroid follicular cells (TFC); Mel was injected alone or
      together with AFB1 (i.p., also once daily for 3 weeks). METHODS: In order to
      assess the process of apoptosis, evaluated in microscopic preparations of rat
      thyroids, an In Situ Cell Death Detection, POD Kit [Roche, GER] and the DAKO
      Liquid DAB Substrate-Chromogen System [DakoCytomation, USA] were employed.
      RESULTS: Aflatoxin B1 increased the apoptotic index (I(apopt)) in rat TFC, in
      comparison to controls (p<0.001). The I(apopt) value in the rats, receiving Mel
      and AFB1 injections, was statistically lower, as compared to the value of the
      examined index in the group of AFB1-treated animals (p<0.001). No statistically
      significant differences of I(apopt) value were observed between the Mel-treated
      group of animals and the controls. CONCLUSION: Melatonin can assumingly regulate
      the growth of cells and tissues by influencing the process of apoptosis.

PMID- 16648799
TI  - Effects of free fatty acids on the course of gestational diabetes mellitus.
AB  - AIM OF THE STUDY: The investigation of the influence of maternal serum free fatty
      acids (FFA) levels on the course of gestational diabetes mellitus (GDM). MATERIAL
      AND METHODS: On the basis of GDM diagnosis 52 diabetic and 39 non-diabetic
      pregnant women were recruited to the study. Treatment modalities for diabetic
      group included diet alone (GDM1; n-36) or a combination of insulin and diet
      (GDM2; n-16). Maternal serum free fatty acids were measured before treatment,
      after 4 weeks therapy, during delivery and in umbilical cord blood. RESULTS:
      Plasma levels of FFA were higher in GDM pregnant women treated later only by diet
      compare with GDM patients required later insulin and non-diabetic gravidas. In
      GDM diet treated group plasma FFA levels progressively decreased with treatment
      duration. The plasma FFA levels in umbilical cord blood did not differ between
      the study groups. We found a positive correlation between maternal venous and
      umbilical cord blood concentration of free fatty acids. Maternal FFA levels
      positively correlated with neonatal births weight. CONCLUSION: Elevated plasma
      FFA levels are associated with GDM and can influence fetal growth. Early and
      intensified GDM treatment may decrease the level of circulating fatty acids.

PMID- 16648800
TI  - Effect of chronic exercise on immunoglobin, complement and leukocyte types in
      volleyball players and athletes.
AB  - BACKGROUND: The objective of this study was to investigate the effect of various
      sports disciplines on basic elements of the acquired and natural defense systems
      and to compare their results with that of non-sporting controls.
      MATERIALS/METHODS: The study included 15 sedentary (Group 1), 15 volleyball
      players (Group 2) and 15 long distance running athletes (Group 3). The VO2 Max
      for the groups was determined by subjecting the individuals to a 20 meter Shuttle
      run test. Immunoglobin and complement levels were measured by the turbidometric
      method. Leukocyte counts were made through peripheral blood smear examination.
      RESULTS: The IgA levels in sedentary living individuals was found to be lower
      than that in volleyball and athlete groups while that in athletes was in turn
      lower than that in volleyball players (p<0.05). In volleyball players the IgG
      level was significantly higher than both the sedentary living individuals and the
      athletes (p<0.05). IgM however, showed a significantly higher level in the
      sedentary group than in both athletes and volleyball players. The C3 levels in
      athletes was significantly lower than that of volleyball players and sedentary
      individuals (p<0.05), while the C4 levels were higher in the volleyball group
      (p<0.05). The leukocyte, eosinophil, and monocyte counts in the athletes were
      also significantly lower than those in the volleyball and sedentary groups
      (p<0.05). The values for the sedentary group on the other hand however, was found
      to be lower than those of the volleyball players (p<0.05). The neutrophil counts
      was lower in the sedentary group than in the volleyball group (p<0.05). The
      levels in the athlete group was lower than that in the volleyball group, however
      (p<0.05). The lymphocyte counts in volleyball players was higher than that in the
      sedentary group (p<0.05). CONCLUSIONS: In conclusion, changes in the immune
      parameters were found to be dependent on the type of physical exercise performed
      on regular basis. Considering the protective antibody response in those
      performing regular sports, moderate exercise carried out on regular basis can be
      said to affect positively mononuclear and polymorphonuclear phagocytic cells--the
      basic elements of the natural immune system.

PMID- 16648801
TI  - Direct effect of cortistatin on GH release from cultured pituitary cells in the
      rat.
AB  - OBJECTIVE: Cortistatin (CST) is a 17-amino acid neuropeptide expressed mainly in
      the cortex and hippocampus. It is also found in the peripheral tissues such as
      the stomach, kidney, pancreas and the immune system. Two forms of cortistatin CST
      17, CST-29 bind with high affinity all somatostatin (SS) receptor subtypes. It
      has been reported that a receptor called MrgX(2) is able to selectively bind both
      CST-17 and CST-14 rather than SS. In human tissues CST-17 and CST-29, rather than
      SS, also bind ghrelin receptor GHS-r1a. In in vivo experiments CST inhibited GH
      and insulin secretion. THE AIM: The aim of this study was to evaluate the effect
      of cortistatin on GH release in in vitro experiments. RESEARCH METHODS: CST-14
      and SS-14 in doses of 1nMol, 10nMol, and 100nMol were added after 48 hrs of
      pituitary cell culture, and the medium was collected 30, 60, 120, 240 min
      thereafter. rGH was measured with RIA kits provided by Linco. RESULTS: CST-14
      stimulated GH release from cultured pituitary cells in a dose dependent manner.
      The maximum effect of CST-14 was observed after 60 min of incubation. However, SS
      14 in doses of 10 nMol and 100 nMol inhibited GH release. CONCLUSION: A direct
      stimulating effect of Cortistatin-14 on GH release from cultured pituitary cells
      was found.

PMID- 16648802
TI  - Developmental programming of the hypothalamus: a matter of insulin. A comment on:
      Horvath, T. L., Bruning, J. C.: Developmental programming of the hypothalamus: a
      matter of fat. Nat. Med. (2006) 12: 52-53.

PMID- 16648803
TI  - dbNEI: a specific database for neuro-endocrine-immune interactions.
AB  - OBJECTIVES: To construct a specific database for the neuro-endocrine-immune (NEI)
      interactions. METHODS/RESULTS: Version 1.0 database for neuro-endocrine-immune
      (dbNEI) serves as a web-based knowledge resource specific for the NEI systems.
      dbNEI collects 1,058 NEI related signal molecules, their 940 interactions and 72
      affiliated tissues from the Cell Signaling Networks database, manually selects
      982 NEI papers from PubMed, and gives links to 27,848 NEI generally related genes
      from UniGene database. NEI related information, such as signal transductions,
      regulations and control subunits, is integrated. Especially, dbNEI represents as
      graphic visualization, by which control subunits can be automatically obtained
      according to the inquiring issues, the combinative queries and the NEI related
      diseases respectively. CONCLUSIONS: dbNEI, which can be accessed at
      http://bioinfo.au.tsinghua.edu.cn/dbNEIweb/, provides a knowledge environment for
      understanding the main regulatory systems of NEI in a molecular level.

PMID- 16648804
TI  - Congenital hypothyroidism in one of monozygotic twins: comparison of their long
      term psychosomatic development.
AB  - Authors present the long-term development of two monozygotic twin sisters. One of
      them was detected by newborn screening as athyreotic (gemelus A) and healthy
      gemelus B sister. Therapy in athyreotic girl started at 4 weeks after birth and
      was monitored in order to maintain serum thyroxine and TSH in normal range. Both
      sisters spent their chilhood and adolescence together in the same family, school
      and work together as tailors in the same factory. Their development was very
      similar. In order to detect subclinical difference of their development, the
      school achievements were tested using their school certificates. Studies were
      divided to testing mechanical memory, logical thinking and skills. The evaluation
      of all classes of school attendance (13 years) reveals subtle differences -
      deficit of patient at approximately 6-15% level, mainly in studies demanding
      skills. However, dynamic evaluation after years reveals that the worse results of
      the patient (gemelus A) occurred during the first years of basic school whereas
      during adolescence having attended the special school tailor, she attained better
      results than her healthy sister. It seems that mental deficit in early treated
      hypothyroid patient is not severe and varies even during the life. Problem of the
      fetal hypothyroidism is probably more related to the iodine deficiency, which
      assures necessity of thyroid hormones for athyreotic child from mother's or
      twin's normally supplemented thyroid glands.

PMID- 16648805
TI  - Clinical, hormonal and sonographic features of the identical twins with
      Klinefelter syndrome--a case report.
AB  - A rare case of Klinefelter syndrome in identical twins is reported. Hormonal
      levels before and after hCG administration and testicular artery Doppler flow
      measurements are presented.

PMID- 16648806
TI  - Circulating cytokines in relation to bone mineral density changes in patients
      with acromegaly.
AB  - OBJECTIVES: Elevated cytokines levels were observed as a marker of increased bone
      resorption in certain diseases. The aim was to assess serum levels of selected
      cytokines in acromegaly, regarding to different disease's stages, gonadal
      function, gender and character of BMD change. METHODS: The study was carried out
      in 62 patients with acromegaly (40 women, 22 men) aged 26-75 years in various
      stages of the disease. The controls were 30 healthy, age- and sex-matched
      subjects. Serum cytokines concentration was assessed using ELISA method. RESULTS:
      We have shown higher (p=0.044) concentrations of TGF-beta in male patients with
      active acromegaly than in cured males. When the influence of all cytokines
      studied on BMD using multiple regression analysis was carried out, the borderline
      (p=0.099) statistical significance was achieved (regression coefficient
      B=0.68271) according to TGF-beta and trochanter major BMD. IL-6 and TNF-alpha
      were higher (p=0.062, and p=0.098, respectively) in these acromegalic patients,
      in which gain of trochanter major BMD occurred. IL-1beta levels were lower in
      patients with ultradistal radius and 1/3 distal radius BMD gain (p=0.007, and
      p=0.009, respectively). Lower TGF-beta levels (p=0.077) were shown in patients
      with 1/3 distal radius gain. IL-6 levels were higher in patients with total body
      BMD gain (p=0.059). CONCLUSIONS: The relations between TGF-beta and acromegaly
      activity in men, and trochanter major BMD in both sexes were documented.
      Concentrations of all cytokines studied correlated with the BMD changes in
      different bone sites. Noteworthy is homogeneity of the secretory character of
      cytokines studied according to BMD changes within particular skeleton sites.

PMID- 16648807
TI  - Cataplexy treated with escitalopram--clinical experience.
AB  - BACKGROUND: Narcolepsy with cataplexy is a debilitating sleep disease of which
      some symptoms can be treated with antidepressants. The antidepressant
      escitalopram is considered the most specific serotonin reuptake inhibitor.
      PATIENTS AND METHODS: Ten patients (5 men and 5 women, age range 18-77 years)
      suffering from narcolepsy with cataplexy occurring at least weekly were treated
      with escitalopram 5 or 10 mg a day for 28-98 days. These patients were barred
      from taking any drugs influencing cataplexy and also had no other diseases
      affecting sleep or vigilance. RESULTS: The mean number of cataplexies per week in
      8 compliant patients declined significantly from 6.7 (+/-SD=7.2) to 0.3 (+/-0.6),
      P=0.02 (Sign test). Cataplexy completely disappeared in 6 patients. Subjective
      daytime sleepiness, power of concentration, quality of night sleep and mood
      remained unchanged. During the treatment, two patients had ejaculation
      disturbances. Two patients withdrew from the therapy (one because of ejaculation
      disturbance, the other for unknown reason). CONCLUSION: Escitalopram proved to
      have anticataplectic effects in this small-scale open-label study.

PMID- 16648808
TI  - Bombesin inhibits LH release in ovariectomized (OVX), estrogen primed rats.
AB  - OBJECTIVE: Bombesin, 14-amino acid peptide, discovered in the gastrointestinal
      tract, is widely distributed in the central nervous system (CNS). The specific
      receptors of bombesin in the pituitary have been characterized. Bombesin plays an
      important role in the gastric and pancreatic secretion, in the mechanism of food
      intake, thermoregulation and in pituitary hormone secretion. There are
      contentious opinions about the effect of bombesin on hormone secretion. THE AIM:
      The aim of this study was to evaluate the effect of estrogens in the modulation
      of bombesin action on LH release. RESEARCH METHODS: Female Wistar-Kyoto rats, two
      weeks after ovariectomy (OVX), were implanted with a cannula being located in the
      third cerebroventricle. Thereafter, the rats were primed with 17beta estradiol in
      a dose of 25microg/0.2ml s.c. for three consecutive days. On the day of the
      experiment, bombesin at a concentration of 0.5 microg in 5microl vehicle
      (artificial cerebrospinal fluid) or equal volume of the vehicle was infused into
      the third ventricle with an automatic pump. At 60 or 120 min after the infusion
      the animals were decapitated, and the trunk blood was collected. Rat serum LH was
      measured by RIA kit supplied by Dr A.F. Parlow from NIDDK Baltimore, MD. RESULTS:
      Bombesin inhibited LH release at 120 min and it did not change LH release at 60
      min after icv administration. CONCLUSIONS: The response of LH release after
      central injection of bombesin is modified by estrogens.

PMID- 16648809
TI  - Atypical pituitary adenoma exhibiting densely secretory granules and basophilia
      without hormone production.
AB  - Herein, we report the case of a 46-year-old male patient with only one month of
      double vision. Radiological examination revealed a pituitary tumor.
      Endocrinological investigations showed no pathological alterations of anterior
      pituitary function. Neuropathological examinations revealed a pituitary gland
      adenoma with an elevated proliferation rate (MIB-1 index 4-5 %) as well as an
      elevated p53 expression leading to the diagnosis of an atypical pituitary
      adenoma. Interestingly, the tumor exhibited strong basophilia in routine
      histology and densely secretory granules in electron microscopy (EM). However, no
      hormone excess was detectable in immunohistochemistry. In contrast to clinical
      and immunohistochemical observations, EM and routine histology findings implied a
      hormone production. This discrepancy might be due to a production of unfunctional
      pre-stages of pituitary gland proteins in this fast growing neoplasm.

PMID- 16648810
TI  - Association study of six activity SNPS in adrenal steroid hormone metabolism and
      IBM related genes with precocious puberty in Chinese girls.
AB  - OBJECTIVES: In order to investigate whether the variances in the candidate genes
      (Insulin receptor substrate IRS-1, beta3-adrenergic receptor ADRB3, 3 beta-hydro
      xysteroid dehydrogenase HSD3B2, glucocorticoid receptor GRL and 21-hydroxylase
      CYP21) which affect the metabolism of adrenal steroids hormone and body
      composition, are associated with precocious puberty in Chinese girls. METHODS:
      PCR-RFLP analysis method was applied in the typing of six activity SNPs in five
      genes in two groups: 176 precocious puberty girls as case and 192 healthy girls
      as control. RESULTS: The typing results showed that the frequencies of the allele
      CYP21 L282 polymorphism were 32.7% and 32.6% in case and control groups
      (P=0.518), respectively. For IRS-1 R972, they were 0.6% in cases and 2.3% in
      controls (P=0.043), for ADRB3 R64, 13.6% in cases and 12% in controls (P=0. 378),
      and for GRL S363, 7.4% in cases and 5.73% in controls (P=0.335). No sample in the
      two groups carries the variation of CYP21 I172N and HSD3B2 L236S. CONCLUSION:
      Among these six activity SNPs in five candidate genes, IRS-1 972R was
      statistically associated with the onset time of puberty in Chinese girls. In
      order to confirm whether the candidate genes have any other activity SNPs that
      are associated with the onset time of puberty in Chinese girls, resequencing of
      these candidate genes is needed in following time.

PMID- 16648811
TI  - Antinociceptive effects of fluoxetine and paroxetine with their related actions
      on glycemia in mice.
AB  - OBJECTIVES: Clinical and experimental trials have demonstrated that some of
      selective serotonin reuptake inhibitors (SSRIs) have some suspicious effects on
      blood glucose levels in different directions. Especially fluoxetine and
      sertraline are studied in this point of view. These drugs are also used in
      treatment of depression and peripheral neuropathy in diabetic patients.
      Paroxetine and fluoxetine, members of this drug group, besides having
      antidepressant effects were shown to have antinociceptive effects in animals and
      humans. They can be used in the treatment of chronic pain as an adjuvant drug or
      alone. But less is known about their actions on pain in case of diabetes. The aim
      of this study is to investigate the antinociceptive effects of fluoxetine and
      paroxetine in diabetic and non-diabetic mice while monitoring their effects on
      blood glucose levels. METHODS: Mice of either sex were randomly used in
      experiments. The antinociceptive effects of paroxetine and fluoxetine were
      evaluated using hot plate test both in diabetic and non-diabetic mice. The
      effects of these drugs on blood glucose levels were also evaluated in another
      group of mice both in diabetic and non-diabetic mice. RESULTS: Fluoxetine and
      paroxetine showed significant antinociceptive effect at all doses and at all
      times tested in non-diabetic mice, but they could not successfully show this
      effect in diabetic mice. They also had controversial effects on blood glucose
      levels. CONCLUSION: Although they showed increasing or decreasing effects on
      blood glucose levels in non-diabetic and diabetic mice, they showed
      antinociception on hot-plate test showing dissociation between blood glucose
      levels and analgesia.

PMID- 16648812
TI  - Antidiuretic hormone release in the bovine: values at rest, and evidence for sex
      differences under stressful conditions including severe hemorrhage.
AB  - OBJECTIVES: This study investigates antidiuretic hormone (ADH) plasma
      concentration in bulls and heifers at rest, after transportation stress, trauma
      and massive hyper-acute hemorrhage at slaughter, with special attention to
      differences between sexes. We also quantified ADH concentration in the ADH
      producing hypothalamic area. SETTING AND DESIGN: The study was carried out on
      animals at the abattoir, exploiting the routinely procedure of slaughtering to
      obtain the experimental stressful conditions. The control group was represented
      by a group of animals matched for breed, age and gender. RESULTS: ADH plasma
      values suggest that transportation stress has little or no effect in heifers in
      contrast to bulls. In both sexes ADH release increases after open head trauma due
      to stunning prior to slaughter. Hemorrhagic hyper-acute stress caused by bleeding
      induces a rapid hundredfold rise of ADH plasma concentration that becomes diergic
      (physiologically different between sexes), with males showing far higher values.
      Females show a higher ADH concentration in the hypothalamus. MAIN FINDING: This
      study points out a difference in ADH output between bulls and heifers under
      conditions of severe hemorrhagic stress, as produced by severing of the neck
      vessels at slaughtering. CONCLUSION: Extreme stress unmasks endocrine differences
      in bovine ADH release that may be relevant only during specific circumstances,
      such as fighting.

PMID- 16648813
TI  - Age-dependent association of exposure to television screen with children's
      urinary melatonin excretion?
AB  - OBJECTIVES: Changes in magnetic field are associated with a decrease in nocturnal
      urinary melatonin excretion. Television screens emit low and very low frequency
      electromagnetic waves (radiofrequencies and light) and exposure to them may be
      associated with a decrease in 24-hour melatonin in children's urine. Design and
      setting. An observational study in schools of Cavriglia, Italy, determined
      melatonin in 24-hour urines from 42 boys and 32 girls 6 to 13 years of age after
      one week of watching TV and after another week of abstaining from watching TV.
      RESULTS AND MAIN FINDINGS: In a gender- and age-dependent fashion, exposure to a
      television screen was associated with lower urinary melatonin concentrations,
      affecting particularly younger children at a pubertal stage when important
      changes in melatonin's time structure occur. CONCLUSION: Additional work should
      test further relations to growth, maturation and development, focusing on any
      adverse effect from exposure to a television screen also on obesity from a neuro
      hormonal viewpoint, quite apart from any decreased activity and/or other
      lifestyle alterations associated with watching TV.

PMID- 16648814
TI  - Age related profiles of free amino acids in human skeletal muscle.
AB  - Sarcopenia describes the involuntary decline in muscle mass with aging, coupled
      with fatigue, and loss of force and function. We investigated 113 human muscle
      biopsy specimens obtained from patients with neuromuscular diseases and controls.
      We measured 21 amino acids in these muscle biopsies. Age emerged as a significant
      negative predictor of cytosolic concentration ratio of glutamine to total
      branched chain amino acids and of glutamine to total aromatic amino acids using
      stepwise multiple linear regression analysis. This pattern of alteration
      corresponds well to documented alterations in skeletal muscle of critically ill
      patients and after immobilization. Additionally, in myositis, citrulline was
      significantly elevated, while glutamate, lysine and taurine were significantly
      reduced. Furthermore, in sporadic amyotrophic lateral sclerosis (sALS) the total
      aromatic amino acids, arginine, glutamate, threonine, and tyrosine were
      significantly elevated. This study provides evidence, that alteration of
      glutamine is correlated to aging and might reflect increased proteolysis in aged
      and diseased human skeletal muscle.

PMID- 16648815
TI  - ACTH-cortisol activity during the 17beta-estradiol and LH preovulatory surges of
      the menstrual cycle.
AB  - OBJECTIVES: A strong positive coupling has been already documented between the
      adrenocortical axis and the gonadal axis at the time of the initiation of the
      preovulatory LH surge of the menstrual cycle in the human. The LH preovulatory
      surge starts in the morning at the time of the acrophase (maximal plasma cortisol
      values) of the cortisol circadian rhythm. Also, it was shown that morning maximal
      plasma cortisol values were higher during the follicular phase than during the
      luteal phase. The objective of the present study was designed to determine the
      exact day of the fall of morning maximal plasma cortisol values and the
      functional correlates which could exist between plasma 17beta-Estradiol, LH, ACTH
      and Cortisol at the time of the preovulatory LH surge. METHODS: We performed a
      detailed analysis of variations of plasma ACTH and cortisol concentrations during
      the various phases of the LH surge: 1) the day before the ascending phase, 2) the
      day of the ascending phase, 3) the day of the LH peak, 4) the day of the
      descending phase, 5) the day after the descending phase. 17beta-Estradiol, LH and
      FSH were determined by microparticle enzyme immunoassays kits and Progesterone
      determination was made using a radioimmunoassay kit. ACTH determination was made
      using a RIA kit and Cortisol was assayed by a RIA method. RESULTS: Plasma ACTH
      concentrations were at their highest the day before the day of the ascending
      phase of the LH surge and significantly higher than the day of the descending
      phase and the day after the day of the descending phase (p < 0.02). Plasma
      cortisol concentrations were at their highest, with almost similar values, the
      day before the day of the ascending phase, the day of the ascending phase and the
      day of the LH peak; then, plasma cortisol concentrations were significantly lower
      than those of the preceding days, the day of the descending phase (p = 0.0001)
      and the day after the day of the descending phase (p = 0.02), when plasma 17beta
      Estradiol starts to decrease. CONCLUSION: Overall, these results suggest that the
      positive ACTH-Cortisol-Estrogen dependency, well documented in the female rat, is
      also operating at midcycle during the menstrual cycle in the human.

PMID- 16648816
TI  - ACTH- and prolactin-producing pituitary gland microadenoma with biphasic features
      of atypia and intermediate filament expression.
AB  - Herein, we report the case of a 28-year old woman clinically presenting with
      unclear weight gain over the last years. The patient displayed facial and neck
      edema in combination with unobtrusive striae distensae. Endocrinological
      examinations led to the diagnosis of Cushing's disease. Neuroradiological
      examination revealed an intrasellar tumor mass of 7 mm in diameter. Subsequently,
      transsphenoidal tumor resection was performed. Histological and
      immunohistochemical investigations revealed a pituitary gland adenoma showing a
      biphasic tumor growth pattern with two morphologically different tumor areas
      producing ACTH and prolactin respectively. Co-expression of ACTH and prolactin is
      exceedingly rare in pituitary adenoma. To our surprise, both tumor areas
      exhibited features of atypia consisting in elevated MIB-1 proliferation index in
      the ACTH-producing portion as well as p53 expression selectively in the prolactin
      producing tumor parts. To our knowledge, this is the first case of an ACTH- and
      prolactin-producing pituitary gland adenoma exhibiting biphasic features of
      atypia.

PMID- 16648817
TI  - A novel polymorphism of the porcine prolactin gene (PRL).
AB  - Prolactin is a protein hormone playing a role in the maintenance of pregnancy in
      the pig by action on corpora lutea cells and possibly initiating production of
      progesterone. The prolactin gene is 10 kb in size and is composed of 5 exons and
      4 introns. The present work is a report of the swine PRL gene--comparative DNA
      sequence analysis and the SNP revealed in the promoter region. Based on the
      bovine prolactin gene, three primer pairs were designed using the Primer3 on-line
      software. The overlapping fragments covered about 400 nucleotides of the promoter
      and 78 nucleotides of exon 1. The fragments were amplified; two of them were
      sequenced and deposited in the GenBank database (AY341908 and AY905690). All
      fragments were analyzed using multitemperature SSCP (MSSCP) technique. Only one
      fragment appeared to show a different MSSCP pattern. The samples of differing
      MSSCP conformers were sequenced and the C499T transition was identified in the
      5'UTR region of the gene. The HphI restriction enzyme appeared to recognize the
      novel SNP. The alignment for homology analysis was performed with porcine, bovine
      (X01452) and human (NM_000948) DNA sequences available in GenBank database, using
      BLAST software. The comparative homology analysis results varied in dependence on
      the species and functional region of the gene.

PMID- 16648818
TI  - Light pollution, reproductive function and cancer risk.
AB  - At present, light pollution (exposure to light-at-night) both in the form of
      occupational exposure during night work and as a personal choice and life style,
      is experienced by numerous night-active members of our society. Disruption of the
      circadian rhythms induced by light pollution has been associated with cancer in
      humans. There are epidemiological evidences of increased breast and colon cancer
      risk in shift workers. An inhibition of the pineal gland function with exposure
      to the constant light (LL) regimen promoted carcinogenesis whereas the light
      deprivation inhibits the carcinogenesis. Treatment with pineal indole hormone
      melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the
      standard light/dark regimen (LD) or at the LL regimen. These observations might
      lead to use melatonin for cancer prevention in groups of humans at risk of light
      pollution.

PMID- 16648819
TI  - Neurobiological implications of eating healthy.
AB  - Over the last decades, the importance of food in the development of chronic
      diseases has been examined, as well as the medical value of eating healthy. The
      contribution of the eating process itself to health and well-being, however, has
      not been questioned until most recently. Biology has linked eating to appetitive
      motivational processes with their underlying neurophysiology, including CNS
      reward circuitries: Eating uses the pleasure-reward physiology to motivate us to
      eat. Endogenous opiates, such as morphine, insure our survival by helping us to
      make eating motivational via pleasure induction. After taking in enough food, we
      become satisfied, i.e., tolerant to food. Our appetite, and so is our appetence,
      are then low and need a certain time span to reach their former levels for then
      inducing food-seeking behaviors, food intake, etc. again. When tolerance passes,
      we once more engage in this pleasurable process related to positive behavioral
      motivation. Opioid receptor agonists, however, may induce energy intake even
      beyond an actual need. This interesting potential of opioidergic signaling may
      have its roots in biological mechanisms that insured the intake and storage of
      high energy foods, hence preparing for future famines. In our world of today,
      however, such neurobiological pathways may pose a threat on our health. Thus,
      feedback mechanisms, such as tolerance, aversion and satiety, have to be finely
      tuned. Therefore central autoregulation that involves, for example, limbic mu
      receptor signaling and other endogenous signaling compounds comes into the focus
      of modern science. The time where research recognizes the importance of
      neurobiological pathways such as endogenous opiate autoregulation or CNS reward
      circuitries for examining the physiology of food intake has yet begun. Many
      questions remain open and have to be answered through future scientific inquiry.

PMID- 16648821
TI  - c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic
      localization.
AB  - c-Abl function is strictly dependent on its subcellular localization. Using an in
      vitro approach, we identify c-Abl as a new substrate for p300, CBP (CREB-binding
      protein) and PCAF (p300/CBP-associated factor) histone acetyltransferases.
      Remarkably, acetylation markedly alters its subcellular localization. Point
      mutagenesis indicated that Lys 730, located in the second nuclear localization
      signal, is the main target of p300 activity. It has previously been reported that
      c-Abl accumulates in the cytoplasm during myogenic differentiation. Here, we show
      that c-Abl protein is acetylated at early stages of myogenic differentiation.
      Indeed, acetylation on Lys 730 drives c-Abl accumulation in the cytoplasm and
      promotes differentiation. Thus, Lys 730 acetylation is a novel post-translational
      modification of c-Abl and a novel mechanism for modulating its subcellular
      localization that contributes to myogenic differentiation.

PMID- 16648822
TI  - Notch targets the Cdk inhibitor Xic1 to regulate differentiation but not the cell
      cycle in neurons.
AB  - The proneural protein neurogenin (XNGNR1) drives differentiation of primary
      neurons in combination with the cyclin-dependent kinase (Cdk) inhibitor Xic1.
      Differentiation is inhibited by Notch signalling, resulting in a scattered
      neuronal distribution. Here we show that Notch signalling regulates the level of
      Xic1 transcription, yet this does not correlate with Notch's ability to perturb
      the cell cycle. Instead, Notch may regulate Xic1 levels to control its
      differentiation function directly, which is required in parallel with XNGNR1 to
      promote primary neurogenesis. Indeed, Notch-mediated repression of both XNGNR1
      and Xic1 must be relieved for neuronal differentiation to occur. Interestingly,
      although Xic1 is required for XNGNR1-mediated neurogenesis, it is not required
      for XNGNR1-mediated upregulation of Delta, allowing establishment of the negative
      feedback loop involved in lateral inhibition. Therefore, Notch targets Cdk
      inhibitor expression to regulate differentiation of primary neurons, and its
      effects on the cell cycle may be of secondary importance.

PMID- 16648823
TI  - Histone modification patterns associated with the human X chromosome.
AB  - X inactivation is associated with chromosome-wide establishment of inactive
      chromatin. Although this is classically regarded as facultative heterochromatin
      that is uniform in nature, the exact distribution of associated epigenetic marks
      is not well defined. Here we have analysed histone modifications in human somatic
      cells within two selected regions of the X chromosome. Intergenic, coding and
      promoter regions are segregated into differentially marked chromatin. H3K27me3 is
      most prominent in intergenic and silenced coding regions, but is associated with
      some active coding regions as well. Histone H3/H4 acetylation and H3K4me3 are
      locally enriched at promoter regions but do not necessarily mark continuing
      transcription. Remarkably, H3K9me3 is predominant in coding regions of active
      genes, a phenomenon that is not restricted to the X chromosome. These results
      argue against the exclusiveness of individual marks to heterochromatin or
      euchromatin, but rather suggest that composite patterns of interdependent or
      mutually exclusive modifications together signal the gene expression status.

PMID- 16648837
TI  - Transforming growth factor-beta induces development of the T(H)17 lineage.
AB  - A new lineage of effector CD4+ T cells characterized by production of interleukin
      (IL)-17, the T-helper-17 (T(H)17) lineage, was recently described based on
      developmental and functional features distinct from those of classical T(H)1 and
      T(H)2 lineages. Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to
      provide adaptive immunity tailored to specific classes of pathogens, such as
      extracellular bacteria. Aberrant T(H)17 responses have been implicated in a
      growing list of autoimmune disorders. T(H)17 development has been linked to IL
      23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL
      12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rbeta1,
      that pairs with unique, inducible components, IL-23R and IL-12Rbeta2, to confer
      receptor responsiveness. Here we identify transforming growth factor-beta (TGF
      beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts
      to upregulate IL-23R expression, thereby conferring responsiveness to IL-23.
      Although dispensable for the development of IL-17-producing T cells in vitro and
      in vivo, IL-23 is required for host protection against a bacterial pathogen,
      Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by
      interferon-gamma and IL-4, thus providing a mechanism for divergence of the
      T(H)1, T(H)2 and T(H)17 lineages.

PMID- 16648838
TI  - Reciprocal developmental pathways for the generation of pathogenic effector TH17
      and regulatory T cells.
AB  - On activation, T cells undergo distinct developmental pathways, attaining
      specialized properties and effector functions. T-helper (T(H)) cells are
      traditionally thought to differentiate into T(H)1 and T(H)2 cell subsets. T(H)1
      cells are necessary to clear intracellular pathogens and T(H)2 cells are
      important for clearing extracellular organisms. Recently, a subset of interleukin
      (IL)-17-producing T (T(H)17) cells distinct from T(H)1 or T(H)2 cells has been
      described and shown to have a crucial role in the induction of autoimmune tissue
      injury. In contrast, CD4+CD25+Foxp3+ regulatory T (T(reg)) cells inhibit
      autoimmunity and protect against tissue injury. Transforming growth factor-beta
      (TGF-beta) is a critical differentiation factor for the generation of T(reg)
      cells. Here we show, using mice with a reporter introduced into the endogenous
      Foxp3 locus, that IL-6, an acute phase protein induced during inflammation,
      completely inhibits the generation of Foxp3+ T(reg) cells induced by TGF-beta. We
      also demonstrate that IL-23 is not the differentiation factor for the generation
      of T(H)17 cells. Instead, IL-6 and TGF-beta together induce the differentiation
      of pathogenic T(H)17 cells from naive T cells. Our data demonstrate a dichotomy
      in the generation of pathogenic (T(H)17) T cells that induce autoimmunity and
      regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury.

PMID- 16648839
TI  - GTP-dependent twisting of dynamin implicates constriction and tension in membrane
      fission.
AB  - Dynamin, a crucial factor in endocytosis, is a member of a family of GTPases that
      participates in membrane fission. It was initially proposed to act as a machine
      that constricts and cuts the neck of nascent vesicles in a GTP-hydrolysis
      dependent reaction, but subsequent studies suggested alternative models. Here we
      monitored the effect of nucleotides on dynamin-coated lipid tubules in real time.
      Addition of GTP, but not of GDP or GTP-gammaS, resulted in twisting of the
      tubules and supercoiling, suggesting a rotatory movement of the helix turns
      relative to each other during GTP hydrolysis. Rotation was confirmed by the
      movement of beads attached to the tubules. Twisting activity produced a
      longitudinal tension that was released by tubule breakage when both ends of the
      tubule were anchored. Fission also occurred when dynamin and GTP were added to
      lipid tubules that had been generated from liposomes by the motor activity of
      kinesin on microtubules. No fission events were observed in the absence of
      longitudinal tension. These findings demonstrate a mechanoenzyme activity of
      dynamin in endocytosis, but also imply that constriction is not sufficient for
      fission. At the short necks of endocytic vesicles, other factors leading to
      tension may cooperate with the constricting activity of dynamin to induce
      fission.

PMID- 16648840
TI  - A fluorescent variant of a protein from the stony coral Montipora facilitates
      dual-color single-laser fluorescence cross-correlation spectroscopy.
AB  - Dual-color fluorescence cross-correlation spectroscopy (FCCS) is a promising
      technique for quantifying protein-protein interactions. In this technique, two
      different fluorescent labels are excited and detected simultaneously within a
      common measurement volume. Difficulties in aligning two laser lines and emission
      crossover between the two fluorophores, however, make this technique complex. To
      overcome these limitations, we developed a fluorescent protein with a large
      Stokes shift. This protein, named Keima, absorbs and emits light maximally at 440
      nm and 620 nm, respectively. Combining a monomeric version of Keima with cyan
      fluorescent protein allowed dual-color FCCS with a single 458-nm laser line and
      complete separation of the fluorescent protein emissions. This FCCS approach
      enabled sensitive detection of proteolysis by caspase-3 and the association of
      calmodulin with calmodulin-dependent enzymes. In addition, Keima and a spectral
      variant that emits maximally at 570 nm might facilitate simultaneous multicolor
      imaging with single-wavelength excitation.

PMID- 16648841
TI  - Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction
      of interferon responses to siRNAs in vitro.
AB  - RNA interference occurs when cytoplasmic small interfering RNAs (siRNAs) enter
      the RNA-induced silencing complex and one strand guides cleavage of the target
      RNA by the Argonaute 2 protein. A significant concern when applying siRNAs or
      expressing small hairpin RNAs (shRNAs) in human cells is activation of the
      interferon (IFN) response. Synthetic siRNAs harboring certain motifs can induce
      an immune response when delivered to mouse and human immune cells such as
      peripheral blood mononuclear cells, monocytes, plasmacytoid dendritic cells
      (pDCs) and nonplasmacytoid dendritic cells (mDCs). In the present study we have
      tested the immunostimulatory effects of lipid-delivered siRNAs versus Pol III
      promoter-expressed shRNAs in primary CD34+ progenitor-derived hematopoietic
      cells. We show that in this system, lipid-delivered siRNAs are potent inducers of
      IFNalpha and type I IFN gene expression, whereas the same sequences when
      expressed endogenously are nonimmunostimulatory.

PMID- 16648842
TI  - A structural basis for discriminating between self and nonself double-stranded
      RNAs in mammalian cells.
AB  - Nonspecific effects triggered by small interfering RNAs (siRNAs) complicate the
      use of RNA interference (RNAi) to specifically downregulate gene expression. To
      uncover the basis of these nonspecific activities, we analyzed the effect of
      chemically synthesized siRNAs on mammalian double-stranded RNA (dsRNA)-activated
      signaling pathways. siRNAs ranging from 21 to 27 nucleotides (nt) in length
      activated the interferon system when they lacked 2-nt 3' overhangs, a
      characteristic of Dicer products. We show that the recognition of siRNAs is
      mediated by the RNA helicase RIG-I and that the presence of 3' overhangs impairs
      its ability to unwind the dsRNA substrate and activate downstream signaling to
      the transcription factor IRF-3. These results suggest a structural basis for
      discrimination between microRNAs that are endogenous Dicer products, and nonself
      dsRNAs such as by-products of viral replication. These findings will enable the
      rational design of siRNAs that avoid nonspecific effects or, alternatively, that
      induce bystander effects to potentially increase the efficacy of siRNA-based
      treatments of viral infections or cancer.

PMID- 16648843
TI  - The NuMA-related Mud protein binds Pins and regulates spindle orientation in
      Drosophila neuroblasts.
AB  - Asymmetric cell division generates cell diversity during development and
      regulates stem-cell self-renewal in Drosophila and mammals. In Drosophila,
      neuroblasts align their spindle with a cortical Partner of Inscuteable (Pins)-G
      alpha i crescent to divide asymmetrically, but the link between cortical polarity
      and the mitotic spindle is poorly understood. Here, we show that Pins directly
      binds, and coimmunoprecipitates with, the NuMA-related Mushroom body defect (Mud)
      protein. Pins recruits Mud to the neuroblast apical cortex, and Mud is also
      strongly localized to centrosome/spindle poles, in a similar way to NuMA. In mud
      mutants, cortical polarity is normal, but the metaphase spindle frequently fails
      to align with the cortical polarity axis. When spindle orientation is orthogonal
      to cell polarity, symmetric division occurs. We propose that Mud is a functional
      orthologue of mammalian NuMA and Caenorhabditis elegans Lin-5, and that Mud
      coordinates spindle orientation with cortical polarity to promote asymmetric cell
      division.

PMID- 16648844
TI  - An interaction between integrin and the talin FERM domain mediates integrin
      activation but not linkage to the cytoskeleton.
AB  - Transmembrane adhesion receptors, such as integrins, mediate cell adhesion by
      interacting with intracellular proteins that connect to the cytoskeleton. Talin,
      one such linker protein, is thought to have two roles: mediating inside-out
      activation of integrins, and connecting extracellular matrix (ECM)-bound
      integrins to the cytoskeleton. Talin's amino-terminal head, which consists of a
      FERM domain, binds an NPxY motif within the cytoplasmic tail of most integrin
      beta subunits. This is consistent with the role of FERM domains in recruiting
      other proteins to the plasma membrane. We tested the role of the talin-head-NPxY
      interaction in integrin function in Drosophila. We found that introduction of a
      mutation that perturbs this binding in vitro into the isolated talin head
      disrupts its recruitment by integrins in vivo. Surprisingly, when engineered into
      the full-length talin, this mutation did not disrupt talin recruitment by
      integrins nor its ability to connect integrins to the cytoskeleton. However, it
      reduced the ability of talin to strengthen integrin adhesion to the ECM,
      indicating that the function of the talin-head-NPxY interaction is solely to
      regulate integrin adhesion.

PMID- 16648845
TI  - Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with
      the APC/C.
AB  - The temporal control of mitotic protein degradation remains incompletely
      understood. In particular, it is unclear why the mitotic checkpoint prevents the
      anaphase-promoting complex/cyclosome (APC/C)-mediated degradation of cyclin B and
      securin in early mitosis, but not cyclin A. Here, we show that another APC/C
      substrate, NIMA-related kinase 2A (Nek2A), is also destroyed in pro-metaphase in
      a checkpoint-independent manner and that this depends on an exposed carboxy
      terminal methionine-arginine (MR) dipeptide tail. Truncation of the Nek2A C
      terminus delays its degradation until late mitosis, whereas Nek2A C-terminal
      peptides interfere with APC/C activity in an MR-dependent manner. Most
      importantly, we show that Nek2A binds directly to the APC/C, also in an MR
      dependent manner, even in the absence of the adaptor protein Cdc20. As similar C
      terminal dipeptide tails promote direct association of Cdc20, Cdh1 and Apc10-Doc1
      with core APC/C subunits, we propose that this sequence also allows a substrate,
      Nek2A, to directly bind the APC/C. Thus, although Cdc20 is required for the
      degradation of Nek2A, it is not required for its recruitment and this renders its
      degradation insensitive to the mitotic checkpoint.

PMID- 16648846
TI  - Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and
      centrosome organization.
AB  - The orientation of the mitotic spindle relative to the cell axis determines
      whether polarized cells undergo symmetric or asymmetric divisions. Drosophila
      epithelial cells and neuroblasts provide an ideal pair of cells to study the
      regulatory mechanisms involved. Epithelial cells divide symmetrically,
      perpendicular to the apical-basal axis. In the asymmetric divisions of
      neuroblasts, by contrast, the spindle reorients parallel to that axis, leading to
      the unequal distribution of cell-fate determinants to one daughter cell. Receptor
      independent G-protein signalling involving the GoLoco protein Pins is essential
      for spindle orientation in both cell types. Here, we identify Mushroom body
      defect (Mud) as a downstream effector in this pathway. Mud directly associates
      and colocalizes with Pins at the cell cortex overlying the spindle pole(s) in
      both neuroblasts and epithelial cells. The cortical Mud protein is essential for
      proper spindle orientation in the two different division modes. Moreover, Mud
      localizes to centrosomes during mitosis independently of Pins to regulate
      centrosomal organization. We propose that Drosophila Mud, vertebrate NuMA and
      Caenorhabditis elegans Lin-5 (refs 5, 6) have conserved roles in the mechanism by
      which G-proteins regulate the mitotic spindle.

PMID- 16648847
TI  - Hippocampal neurogenesis is not required for behavioral effects of environmental
      enrichment.
AB  - Environmental enrichment increases adult hippocampal neurogenesis and alters
      hippocampal-dependent behavior in rodents. To investigate a causal link between
      these two observations, we analyzed the effect of enrichment on spatial learning
      and anxiety-like behavior while blocking adult hippocampal neurogenesis. We
      report that environmental enrichment alters behavior in mice regardless of their
      hippocampal neurogenic capability, providing evidence that the newborn cells do
      not mediate these effects of enrichment.

PMID- 16648848
TI  - Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle
      endocytosis.
AB  - Dynamin I is dephosphorylated at Ser-774 and Ser-778 during synaptic vesicle
      endocytosis (SVE) in nerve terminals. Phosphorylation was proposed to regulate
      the assembly of an endocytic protein complex with amphiphysin or endophilin.
      Instead, we found it recruits syndapin I for SVE and does not control amphiphysin
      or endophilin binding in rat synaptosomes. After depolarization, syndapin showed
      a calcineurin-mediated interaction with dynamin. A peptide mimicking the
      phosphorylation sites disrupted the dynamin-syndapin complex, not the dynamin
      endophilin complex, arrested SVE and produced glutamate release fatigue after
      repetitive stimulation. Pseudophosphorylation of Ser-774 or Ser-778 inhibited
      syndapin binding without affecting amphiphysin recruitment. Site mutagenesis to
      alanine arrested SVE in cultured neurons. The effects of the sites were additive
      for syndapin I binding and SVE. Thus syndapin I is a central component of the
      endocytic protein complex for SVE via stimulus-dependent recruitment to dynamin I
      and has a key role in synaptic transmission.

PMID- 16648849
TI  - Distinct timing in the activity of cannabinoid-sensitive and cannabinoid
      insensitive basket cells.
AB  - Cannabinoids are powerful modulators of inhibition, yet the precise spike timing
      of cannabinoid receptor (CB1R)-expressing inhibitory neurons in relation to other
      neurons in the circuit is poorly understood. Here we found that the spike timing
      of CB1R-expressing basket cells, a major target for cannabinoids in the rat
      hippocampus, was distinct from the other main group of basket cells, the CB1R
      negative. Despite receiving the same afferent inputs, the synaptic and
      biophysical properties of the two cell types were tuned to detect different
      features of activity. CB1R-negative basket cells responded reliably and
      immediately to subtle and repetitive excitation. In contrast, CB1R-positive
      basket cells responded later and did not follow repetitive activity, but were
      better suited to integrate the consecutive excitation of independent afferents.
      This temporal separation in the activity of the two basket cell types generated
      distinct epochs of somatic inhibition that were differentially affected by
      endocannabinoids.

PMID- 16648850
TI  - A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac
      repolarization.
AB  - Extremes of the electrocardiographic QT interval, a measure of cardiac
      repolarization, are associated with increased cardiovascular mortality. We
      identified a common genetic variant influencing this quantitative trait through a
      genome-wide association study on 200 subjects at the extremes of a population
      based QT interval distribution of 3,966 subjects from the KORA cohort in Germany,
      with follow-up screening of selected markers in the remainder of the cohort. We
      validated statistically significant findings in two independent samples of 2,646
      subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This
      genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide
      synthase, as a new target that modulates cardiac repolarization. Approximately
      60% of subjects of European ancestry carry at least one minor allele of the
      NOS1AP genetic variant, which explains up to 1.5% of QT interval variation.

PMID- 16648851
TI  - Mutations in the gene encoding the PML nuclear body protein Sp110 are associated
      with immunodeficiency and hepatic veno-occlusive disease.
AB  - We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno
      occlusive disease with immunodeficiency, an autosomal recessive disorder of
      severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent
      lymph node germinal centers, absent tissue plasma cells and hepatic veno
      occlusive disease. This is the first report of the involvement of a nuclear body
      protein in a human primary immunodeficiency and of high-penetrance genetic
      mutations in hepatic veno-occlusive disease.

PMID- 16648852
TI  - Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin
      1beta in salmonella-infected macrophages.
AB  - Gram-negative bacteria that replicate in the cytosol of mammalian macrophages can
      activate a signaling pathway leading to caspase-1 cleavage and secretion of
      interleukin 1beta, a powerful host response factor. Ipaf, a cytosolic pattern
      recognition receptor in the family of nucleotide-binding oligomerization domain
      leucine-rich repeat proteins, is critical in such a response to salmonella
      infection, but the mechanism of how Ipaf is activated by the bacterium remains
      poorly understood. Here we demonstrate that salmonella strains either lacking
      flagellin or expressing mutant flagellin were deficient in activation of caspase
      1 and in interleukin 1beta secretion, although transcription factor NF-kappaB
      dependent production of interleukin 6 or the chemokine MCP-1 was unimpaired.
      Delivery of flagellin to the macrophage cytosol induced Ipaf-dependent activation
      of caspase-1 that was independent of Toll-like receptor 5, required for
      recognition of extracellular flagellin. In macrophages made tolerant by previous
      exposure to lipopolysaccharide, which abrogates activation of NF-kappaB and
      mitogen-activated protein kinases, salmonella infection still activated caspase
      1. Thus, detection of flagellin through Ipaf induces caspase-1 activation
      independently of Toll-like receptor 5 in salmonella-infected and
      lipopolysaccharide-tolerized macrophages.

PMID- 16648853
TI  - Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via
      Ipaf.
AB  - Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine
      rich repeat family member that activates caspase-1 and secretion of interleukin
      1beta. However, the specific microbial salmonella-derived agonist responsible for
      activating Ipaf is unknown. We show here that cytosolic bacterial flagellin
      activated caspase-1 through Ipaf but was independent of Toll-like receptor 5, a
      known flagellin sensor. Stimulation of the Ipaf pathway in macrophages after
      infection required a functional salmonella pathogenicity island 1 type III
      secretion system but not the flagellar type III secretion system; furthermore,
      Ipaf activation could be recapitulated by the introduction of purified flagellin
      directly into the cytoplasm. These observations raise the possibility that the
      salmonella pathogenicity island 1 type III secretion system cannot completely
      exclude 'promiscuous' secretion of flagellin and that the host capitalizes on
      this 'error' by activating a potent host-defense pathway.

PMID- 16648854
TI  - Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin
      regulates antigen receptor-mediated lipid raft dynamics.
AB  - Ligation of the B cell antigen receptor (BCR) with antigen induces lipid raft
      coalescence, a process that occurs after crosslinking of a variety of signaling
      receptors and is thought to potentiate cellular activation. To investigate lipid
      raft dynamics during BCR signaling, we quantitatively analyzed the B cell lipid
      raft proteome. BCR engagement induced dissociation of the adaptor protein ezrin
      from lipid rafts as well as threonine dephosphorylation of ezrin and its
      concomitant detachment from actin, indicating a transient uncoupling of lipid
      rafts from the actin cytoskeleton. Expression of constitutively active ezrin
      chimeras inhibited the BCR-induced coalescence of lipid rafts. Our data
      demonstrate that the release of ezrin from lipid rafts acts as a critical trigger
      that regulates lipid raft dynamics during BCR signaling.

PMID- 16648855
TI  - Lysophospholipid sensing triggers secretion of flagellin from pathogenic
      salmonella.
AB  - Flagellin induces inflammatory and innate immune responses through activation of
      Toll-like receptor 5. Here we show that proinflammatory monomeric flagellin
      produced by salmonella during infection of intestinal epithelial cells was not
      derived from polymeric bacterial cell wall-associated flagellum but instead was
      synthesized and secreted de novo by the bacterium after direct sensing of host
      produced lysophospholipids. Inhibition of lysophospholipid biosynthesis in
      intestinal epithelial cells reduced flagellin production and release from
      salmonella. Lysophospholipids induced a cAMP-dependent signaling pathway in
      salmonella that resulted in production and secretion of active flagellin. The
      induction of Toll-like receptor ligand synthesis and secretion by a host signal
      represents a previously unknown regulatory mechanism for inflammation and innate
      immunity during infection with a bacterial pathogen.

PMID- 16648856
TI  - Ultrasonic metamaterials with negative modulus.
AB  - The emergence of artificially designed subwavelength electromagnetic materials,
      denoted metamaterials, has significantly broadened the range of material
      responses found in nature. However, the acoustic analogue to electromagnetic
      metamaterials has, so far, not been investigated. We report a new class of
      ultrasonic metamaterials consisting of an array of subwavelength Helmholtz
      resonators with designed acoustic inductance and capacitance. These materials
      have an effective dynamic modulus with negative values near the resonance
      frequency. As a result, these ultrasonic metamaterials can convey acoustic waves
      with a group velocity antiparallel to phase velocity, as observed experimentally.
      On the basis of homogenized-media theory, we calculated the dispersion and
      transmission, which agrees well with experiments near 30 kHz. As the negative
      dynamic modulus leads to a richness of surface states with very large
      wavevectors, this new class of acoustic metamaterials may offer interesting
      applications, such as acoustic negative refraction and superlensing below the
      diffraction limit.

PMID- 16648857
TI  - Long-range resonantly enhanced triplet formation in luminescent polymers doped
      with iridium complexes.
AB  - The current drive to produce cheap, flexible plastic displays has led to rapid
      improvements in device efficiency. Inclusion of highly phosphorescent heavy-metal
      organic complexes as dopants ensures that both singlet and triplet excitations
      formed on charge recombination can be used efficiently to emit light. However,
      the inclusion of these dopants affects the photophysics of the host in a
      surprising way, generating a ten- to twenty- fold instantaneous increase in the
      number of host triplet states, independent of host triplet energy, quenching up
      to 95% of all singlet states. Once created however, these triplets are only
      weakly quenched by the same mechanism. We ascribe this to a resonant, remote
      intermolecular heavy-atom effect that greatly increases the inter-system crossing
      rate of the host polymer arising through the strong overlap of the delocalized pi
      orbitals of the host and ligands. This mechanism competes effectively with
      Forster energy transfer, and operates over large distances.

PMID- 16648858
TI  - Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis and
      tumor formation.
AB  - The growing number of recently identified negative feedback regulators of
      receptor tyrosine kinases (RTKs) highlights the importance of signal attenuation
      and modulation for correct signaling outcome. Mitogen-inducible gene 6 (Mig6 also
      known as RALT or Gene 33) is a multiadaptor protein thought to be involved in the
      regulation of RTK and stress signaling. Here, we show that deletion of the mouse
      gene encoding Mig6 (designated Errfi1, which stands for ERBB receptor feedback
      inhibitor 1) causes hyperactivation of endogenous epidermal growth factor
      receptor (EGFR) and sustained signaling through the mitogen-activated protein
      kinase (MAPK) pathway, resulting in overproliferation and impaired
      differentiation of epidermal keratinocytes. Furthermore, Errfi1-/- mice develop
      spontaneous tumors in various organs and are highly susceptible to chemically
      induced formation of skin tumors. A tumor-suppressive role for Mig6 is supported
      by our finding that MIG6 is downregulated in various human cancers. Inhibition of
      endogenous Egfr signaling with the Egfr inhibitor gefitinib (Iressa) or
      replacement of wild-type Egfr with the kinase-deficient protein encoded by the
      hypomorphic Egfr(wa2) allele completely rescued skin defects in Erffi1-/- mice.
      Carcinogen-induced tumors displayed by Errfi1-/- mice were highly sensitive to
      gefitinib. These results indicate that Mig6 is a specific negative regulator of
      Egfr signaling in skin morphogenesis and is a novel tumor suppressor of Egfr
      dependent carcinogenesis.

PMID- 16648860
TI  - Peptide bond formation does not involve acid-base catalysis by ribosomal
      residues.
AB  - Ribosomes catalyze the formation of peptide bonds between aminoacyl esters of
      transfer RNAs within a catalytic center composed of ribosomal RNA only. Here we
      show that the reaction of P-site formylmethionine (fMet)-tRNA(fMet) with a
      modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino
      group is replaced with a hydroxyl group, does not show the pH dependence observed
      with small substrate analogs such as puromycin and hydroxypuromycin. This
      indicates that acid-base catalysis by ribosomal residues is not important in the
      reaction with the full-size substrate. Rather, the ribosome catalyzes peptide
      bond formation by positioning the tRNAs, or their 3' termini, through
      interactions with rRNA that induce and/or stabilize a pH-insensitive conformation
      of the active site and provide a preorganized environment facilitating the
      reaction. The rate of peptide bond formation with unmodified Phe-tRNA(Phe) is
      estimated to be >300 s(-1).

PMID- 16648861
TI  - Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid.
AB  - Isoniazid is a key drug used in the treatment of tuberculosis. Isoniazid is a pro
      drug, which, after activation by the katG-encoded catalase peroxidase, reacts
      nonenzymatically with NAD(+) and NADP(+) to generate several isonicotinoyl
      adducts of these pyridine nucleotides. One of these, the acyclic 4S isomer of
      isoniazid-NAD, targets the inhA-encoded enoyl-ACP reductase, an enzyme essential
      for mycolic acid biosynthesis in Mycobacterium tuberculosis. Here we show that
      the acyclic 4R isomer of isoniazid-NADP inhibits the M. tuberculosis
      dihydrofolate reductase (DHFR), an enzyme essential for nucleic acid synthesis.
      This biologically relevant form of the isoniazid adduct is a subnanomolar
      bisubstrate inhibitor of M. tuberculosis DHFR. Expression of M. tuberculosis DHFR
      in Mycobacterium smegmatis mc(2)155 protects cells against growth inhibition by
      isoniazid by sequestering the drug. Thus, M. tuberculosis DHFR is the first new
      target for isoniazid identified in the last decade.

PMID- 16648859
TI  - Cytokine-mediated deployment of SDF-1 induces revascularization through
      recruitment of CXCR4+ hemangiocytes.
AB  - The mechanisms through which hematopoietic cytokines accelerate revascularization
      are unknown. Here, we show that the magnitude of cytokine-mediated release of SDF
      1 from platelets and the recruitment of nonendothelial CXCR4+ VEGFR1+
      hematopoietic progenitors, 'hemangiocytes,' constitute the major determinant of
      revascularization. Soluble Kit-ligand (sKitL), thrombopoietin (TPO, encoded by
      Thpo) and, to a lesser extent, erythropoietin (EPO) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) induced the release of SDF-1 from platelets,
      enhancing neovascularization through mobilization of CXCR4+ VEGFR1+
      hemangiocytes. Although revascularization of ischemic hindlimbs was partially
      diminished in mice deficient in both GM-CSF and G-CSF (Csf2-/- Csf3-/-), profound
      impairment in neovascularization was detected in sKitL-deficient Mmp9-/- as well
      as thrombocytopenic Thpo-/- and TPO receptor-deficient (Mpl-/-) mice. SDF-1
      mediated mobilization and incorporation of hemangiocytes into ischemic limbs were
      impaired in Thpo-/-, Mpl-/- and Mmp9-/- mice. Transplantation of CXCR4+ VEGFR1+
      hemangiocytes into Mmp9-/- mice restored revascularization, whereas inhibition of
      CXCR4 abrogated cytokine- and VEGF-A-mediated mobilization of CXCR4+ VEGFR1+
      cells and suppressed angiogenesis. In conclusion, hematopoietic cytokines,
      through graded deployment of SDF-1 from platelets, support mobilization and
      recruitment of CXCR4+ VEGFR1+ hemangiocytes, whereas VEGFR1 is essential for
      their angiogenic competency for augmenting revascularization. Delivery of SDF-1
      may be effective in restoring angiogenesis in individuals with vasculopathies.

PMID- 16648862
TI  - Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and
      PU.1 in Hodgkin's and non-Hodgkin's lymphomas: a comparative study using high
      throughput tissue microarrays.
AB  - Analysis of B-cell-specific transcription factors is useful in understanding of
      the differentiation-linked phenotype in Hodgkin's as well as in non-Hodgkin's
      lymphomas. We analyzed the expression profiling of transcription factors Pax-5,
      Oct-1, Oct-2, BOB.1, and PU.1 in 109 cases, including non-Hodgkin's lymphomas of
      B- and T-lineage, classical Hodgkin's lymphomas, and nodular lymphocyte
      predominant Hodgkin's lymphomas. Our study revealed that all transcription
      factors were universally expressed in all cases of nodular lymphocyte predominant
      Hodgkin's and variably expressed in non-Hodgkin's lymphomas of B-lineage. Cases
      of classical Hodgkin's lymphoma variably expressed the Pax-5, Oct-1, Oct-2, and
      BOB.1. However, in contrast to nodular lymphocyte predominant Hodgkin's lymphoma,
      the transcription factor PU.1 was consistently absent in all cases of classical
      Hodgkin's lymphoma. Transcription factors Pax-5, BOB.1, and PU.1 were not
      detectable in cases of anaplastic large cell lymphoma. However, the Oct-1 was
      detected in all anaplastic large cells lymphoma cases, indicating that expression
      of this transcription factor was not restricted to B-lineage lymphoid
      malignancies. Our findings suggest that inclusion of the PU.1 antibody may prove
      useful in separating classical Hodgkin's lymphomas from nodular lymphocyte
      predominant Hodgkin's lymphomas in problematic cases.

PMID- 16648863
TI  - Cyclin D1 protein overexpression and CCND1 amplification in breast carcinomas: an
      immunohistochemical and chromogenic in situ hybridisation analysis.
AB  - Conflicting results on the prevalence of cyclin D1 ovexpression and its
      correlation with CCND1 amplification and outcome of breast cancer patients have
      been reported. Owing to limited sensitivity and specificity of most antibodies
      against cyclin D1, evaluation of cyclin D1 immunoexpression is reported to be
      problematic. The aims of this study were to assess the prevalence of cyclin D1
      expression in breast carcinomas using the SP4 rabbit monoclonal antibody; to
      correlate cyclin D1 expression with amplification, assessed using chromogenic in
      situ hybridisation (CISH); and to analyse the relationship between CCND1
      amplification and overexpression with clinicopathological parameters and outcome
      in a tissue microarray containing replicate tumour samples from 245 breast cancer
      patients. Immunohistochemistry for cyclin D1 was performed using the SP4 and the
      results were scored according to the Allred scoring system. CISH was carried out
      using the Zymed CCND1 SpotLight probe. CISH signals were counted in 60
      morphologically unequivocal neoplastic cells. Amplification was defined as >5
      signals per nucleus in more than 50% of cancer cells, or when large gene copy
      clusters were seen. Strong cyclin D1 expression and CCND1 amplification were
      found in 67.4 and 14.5% of the cases, respectively. A strong correlation between
      cyclin D1 overexpression and CCND1 amplification was demonstrated (P<0.0001).
      Cyclin D1 expression showed a positive correlation with hormone receptor
      expression (both ER and PgR, P<0.0001). An inverse correlation was observed
      between an immunohistochemical panel of 'basal-like' markers and both cyclin D1
      overexpression (P<0.0001) and CCND1 amplification (P<0.0001). On univariate
      analysis cyclin D1 expression showed a correlation with longer overall survival
      (OS). Neither cyclin D1 nor CCND1 were independent prognostic factors for disease
      free survival or OS. The results of this study confirm the association between
      cyclin D1 overexpression and positivity for hormone receptors and the lack of
      CCND1 amplification in basal-like breast carcinomas.

PMID- 16648864
TI  - Immunophenotypic diversity of endometrial adenocarcinomas: implications for
      differential diagnosis.
AB  - Many endometrial adenocarcinomas, particularly those of endometrioid type,
      express estrogen receptors (ERs), progesterone receptors (PRs), and vimentin.
      This typical immunophenotype is frequently considered a standard against which
      others are compared when immunohistochemistry is used for differential diagnosis.
      We tested large numbers of endometrial cancers, enriched for high-grade tumors,
      to determine whether this reported immunophenotype was valid and whether
      expression differences between types of endometrial carcinoma could be exploited
      for diagnostic purposes. Immunohistochemical stains were performed on the
      following types of endometrial cancers using established methodology:
      International Federation of Gynecology and Obstetrics (FIGO) grades 1 and 2
      endometrioid-42; FIGO grade 3 endometrioid-40; serous-24; clear cell-11;
      carcinosarcoma-9. In total, 92% of serous carcinomas expressed p16 strongly
      compared to weak-to-moderate expression of p16 in 7-67% of other tumors (FIGO
      grades 1 and 2 carcinoma and carcinosarcoma, respectively). A total of 84% of
      FIGO grades 1 and 2 carcinomas expressed ER compared to 9-54% of other tumors
      (clear cell and serous carcinomas respectively); 83% of FIGO grades 1 and 2
      expressed PR compared to 11-54% of other carcinomas (carcinosarcoma and serous
      carcinoma, respectively). Most carcinomas were negative for monoclonal
      carcinoembryonic antigen (mCEA), and those that were positive showed mostly only
      focal membrane expression. Vimentin was expressed in nearly every tumor. Most
      tumors were diffusely vimentin positive, but a large range of expression
      patterns, from focal to diffuse and from weak to strong, was noted. Only 70% of
      FIGO grades 1 and 2 endometrioid carcinomas and 26% of grade 3 endometrioid
      carcinomas possessed the reportedly characteristic endometrial cancer
      immunophenotype p16 (-), ER (+), PR (+), mCEA (-), and vimentin (+). Endometrial
      cancers demonstrate substantial immunophenotypic diversity that remained apparent
      even within groups of similar histologic subtype and grade. ER, PR, and p16
      expression was more illustrative of tumor type and degree of differentiation than
      they were of endometrial origin. In contrast, the vimentin-positive/CEA-negative
      phenotype remained the most constant among all endometrial cancers.

PMID- 16648865
TI  - Diversity of epidermal growth factor receptor-mediated activation of downstream
      molecules in human lung carcinomas.
AB  - The correlations among epidermal growth factor receptor (EGFR) gene
      amplification, gene mutation, overexpression/phosphorylation of EGFR protein and
      activation of its downstream molecules, signal transducers and activators of
      transcription 3 (Stat-3), Akt and extracellular signal-related protein kinase 1/2
      (Erk1/2) were investigated in 28 cases of human lung carcinomas. In five cases of
      carcinomas with EGFR amplification, EGFR expression and phosphorylation levels
      were higher than other cases, and Stat-3 was activated in all five cases. Point
      mutations in the tyrosine kinase domain of EGFR were detected in five cases, one
      of which was also associated with gene amplification. In these five cases, both
      EGFR expression and phosphorylation were enhanced, and Akt was activated in four
      cases. In the remaining 19 cases, EGFR protein expression was upregulated in
      eight cases and phosphorylated in four cases, but neither EGFR nor phosphorylated
      EGFR expression levels specifically correlated with activation of particular
      downstream molecules. In general, either Stat-3 or Akt, but not both, was
      activated reciprocally and complementarily to each other, as indicated by their
      phosphorylation. However, Erk1/2 was activated regardless of the status of Stat
      3, Akt or EGFR proteins. The current data suggest that persistent Stat-3
      activation may be a critical event downstream of EGFR that has been overexpressed
      by gene amplification. In contrast, tumor cells harboring the EGFR mutation may
      persistently activate a cascade via Akt. Finally, in the majority of cases that
      have no aberration of the EGFR, its downstream molecules function in reciprocal
      and/or complementary manner in the maintenance and/or progression of carcinomas.
      These overall results could provide novel insights into potential
      chemotherapeutic regimens for lung carcinomas, such as inhibitors of Stat-3, Akt
      and Erk1/2.

PMID- 16648866
TI  - Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas
      and predict metastasis?
AB  - DNA copy number changes were investigated in 51 (19 uterine and 32 nonuterine)
      primary leiomyosarcomas by comparative genomic hybridization. The aim was to
      evaluate whether true biological differences exist between uterine and nonuterine
      leiomyosarcoma and whether changes revealed by comparative genomic hybridization
      have prognostic value. Genomic imbalances were found in 48 (94%) cases. The most
      frequent DNA copy number changes were losses in 10q (35%), 13q (57%), and 16q
      (41%), gains in 1q (41%), and gains and high-level amplifications in 17p (39%).
      Gains were nearly as frequent as losses in both uterine and nonuterine
      leiomyosarcoma. Correlation-based tree modeling revealed two clusters that
      segregated significantly a group of uterine (gains at 1q11-q24) and a group of
      nonuterine (losses at 13q14-q34, 16q11.1-q24, and 10q21-q26) cases. The
      nonuterine cluster was associated with subcutaneous origin and a trend toward
      increased metastasis-free survival. Further explorative analyses identified
      aberrations associated with shorter metastasis-free survival time, including
      losses at 2q32.1-q37 and gains at 8q24.1-q24.3, whereas the cases with losses at
      6cen-p25 showed longer metastasis-free survival time.

PMID- 16648867
TI  - D2-40 antibody immunoreactivity in developing human brain, brain tumors and
      cultured neural cells.
AB  - D2-40 antibody is raised against an oncofetal antigen, the M2A antigen. It has
      been used as a marker for lymphatic endothelium as well as mesothelioma and
      cerebellar hemangioblastoma. We demonstrate here that positive D2-40
      immunoreactivity was found in the developing cerebrum, particularly in the
      germinal matrix layer, immature ependyma, choroid plexus and meninges. In the
      developing cerebellum, positive D2-40 immunoreactivity was found in the external
      granular layer particularly of the outer portion and the Purkinje cell layer as
      well as meninges. Some brain tumors such as anaplastic ependymoma, some
      medulloblastomas, glioblastoma, pineal germinoma, craniopharyngioma, choroid
      plexus papilloma, choroid plexus carcinoma, and meningioma showed positive
      immunoreactivity with D2-40. Therefore, D2-40 antibody is considered a useful
      marker for research on developing brain and diagnosis of brain tumors,
      differentiation between choroid plexus carcinoma and metastatic carcinoma. In
      addition, on cultured human neural cells, D2-40 immunoreactivity was found in
      nestin-positive neural stem/progenitor cells and neuronal lineage cells. As D2-40
      antibody recognizes cell surface antigen M2A, it might be a candidate cell
      surface marker for isolation of human neural stem cells/neuronal lineage cells in
      the fluorescence-activated cell sorting technique.

PMID- 16648868
TI  - Clinicopathologic implications of tissue inhibitor of metalloproteinase-1
      positive diffuse large B-cell lymphoma.
AB  - The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that
      promotes plasmablastic differentiation, and the survival of germinal center B
      cells. The expression of TIMP-1 is known to be correlated with a subset of non
      Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To
      characterize TIMP-1(+) diffuse large B-cell lymphoma, TIMP-1 expression was
      investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell
      lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr
      virus infection status. TIMP-1 was expressed not only in tumor cells themselves,
      in 14 of 182 cases (8%), designated as TIMP-1(+) diffuse large B-cell lymphoma,
      but also in stromal cells like fibroblasts and endothelial cells. In univariate
      analysis and hierarchical clustering, our findings suggest that TIMP-1 expression
      may represent a distinct subgroup. In multivariate analysis, TIMP-1(+) diffuse
      large B-cell lymphoma (n=14) was associated with unfavorable outcomes compared to
      TIMP-1(-) diffuse large B-cell lymphoma (n=168) (odds ratio=2.5, P=0.049).
      Together with TIMP-1 expression, age (greater than 60 years), the presence of B
      symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV)
      was correlated with a poor overall survival. However, TIMP-1 expression in
      diffuse large B-cell lymphoma was not correlated with other prognostic factors
      including: clinical stage, international prognostic index score, and nongerminal
      center B-cell phenotype, as well as Epstein-Barr virus infection. Our results
      suggest that TIMP-1 expression may be an independent negative prognostic factor
      in patients with diffuse large B-cell lymphoma.

PMID- 16648869
TI  - Chromosomal imbalances in clear cell ependymomas.
AB  - Clear cell ependymoma is a rare and diagnostically challenging subtype of
      ependymoma, whose genetic features are essentially unknown. We studied 13 clear
      cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by
      comparative genomic hybridization (CGH). Chromosomal imbalances were found in
      12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3
      (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized
      by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%),
      as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal
      tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO
      grade III samples (1.4 vs 3.5 per case). Although some of the implicated
      chromosomes have previously been shown to be involved in other ependymoma
      variants, the striking frequency of +1q, -9, and -3 suggests that aberrations
      differ between clear cell and other types of ependymomas, in particular, for loss
      of chromosome 9 which can be regarded as the molecular hallmark of clear cell
      ependymomas.

PMID- 16648870
TI  - Expression of epidermal growth factor receptor in squamous cell carcinomas of the
      anal canal is independent of gene amplification.
AB  - Immunohistochemical detection of expression of the epidermal growth factor
      receptor (EGFR) has been utilized to identify eligible patients with solid
      malignant tumors, including colorectal adenocarcinoma, for monoclonal antibody
      therapy (eg, cetuximab). The EGFR status in squamous cell carcinoma of the anal
      canal, an uncommon malignancy traditionally treated with chemoradiation, has not
      been well investigated. In this study, 38 primary squamous cell carcinomas of the
      anal canal were immunohistochemically examined for EGFR expression and analyzed
      by fluorescence in situ hybridization (FISH) for EGFR gene copy numbers. The
      results showed a variable degree of EGFR expression in 21 (55%) tumors, among
      which 13 (62%) cases exhibited a 2+ to 3+ staining pattern according to the Dako
      EGFR phamDx interpretation guide. There were no significant differences among
      tumors stratified by stage, degree of keratinization, or tissue block storage
      times. FISH analysis showed that none of the 34 cases with interpretable results
      had EGFR gene amplification. Increased gene copy numbers due to polysomy 7 were
      seen in seven of 18 (39%) cases that expressed EGFR protein and four of 16 (25%)
      cases that did not (P=0.3876). Ten (56%) tumors with positive EGFR staining
      showed a balanced disomy 7 pattern and one case with monosomy 7 exhibited strong
      EGFR expression (3+). These results demonstrate that EGFR is overexpressed in
      more than one-half of the squamous cell carcinomas of the anal canal through
      mechanisms other than gene amplification. These observations may have important
      therapeutic implications since EGFR-based targeted therapies have shown promise
      for other malignant neoplasms.

PMID- 16648871
TI  - Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas
      with shorter failure-free survival.
AB  - Ocular adnexa B-cell lymphomas are a relatively rare group of extranodal
      lymphomas, marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue
      (MALT lymphomas) being the most frequent type at this location. As with other
      nongastrointestinal MALT lymphomas, ocular adnexa MALT lymphomas have distinct
      characteristics from those of the gastric MALT model, implying specific
      pathogenic events, which could be of interest in the prediction of clinical
      behavior and the choice between therapeutic options. In a series of 39 cases of
      ocular adnexa MALT lymphomas, studied using a tissue microarray, we observed that
      the most frequent alteration was related to apoptosis regulation. Thus, caspase 3
      activity was completely abolished, and phosphorylated IkappaBalpha, a marker of
      NF-kappaB activation, showed increased expression, while cases with an increased
      number of large cells displayed increased expression of survivin and other cell
      cycle-related proteins, such as cyclin A, cyclin E and Ki67, and p16 expression
      was reduced. There were no occurrences of t(11;18)(q21,q21), while 5/37 cases
      exhibited t(14;18)(q32;q21). Aberrant nuclear expression of bcl10 was observed in
      11 cases, independently of the presence of translocations, and was significantly
      associated with phosphorylated IkappaBalpha expression and a reduced TdT-mediated
      biotin-dUTP nicked-end labeling apoptotic index. Moreover, patients with tumoral
      bcl10 nuclear expression showed shorter failure-free survival.

PMID- 16648872
TI  - Determination of sequential mutation accumulation in pancreas and bile duct
      brushing cytology.
AB  - Neoplastic progression is characterized by clonal expansion of tumor cells
      associated with accumulation of mutational damage. The timing of mutation
      acquisition could be of value in distinguishing preneoplastic conditions from
      early and advanced cancer as well as characterizing tumor aggressiveness and
      treatment response. Using quantitative methods applied to microdissected cell
      clusters selected according to cytomorphologic features, we sought to demonstrate
      the feasibility and efficacy for determining the time and course of mutation
      accumulation in pancreatobiliary cytology specimens. In all, 40 pancreatic duct
      and 21 biliary brushing cytology specimens were retrieved from the cytology
      database. Xylene-resistant markings were placed on the slide underside and
      coverslips removed. Clusters of benign, atypical and malignant cells were
      manually microdissected and DNA extracted. Mutations (allelic imbalance) (loss of
      heterozygosity) were quantitatively determined for a broad panel of 15 markers
      (1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q) as well as point mutation in K-ras-2
      using PCR/capillary electrophoresis. Time course was based on earlier mutations
      having a higher proportion of mutant DNA for a particular marker. The descending
      frequency of detectable mutational involvement in pancreatic cytology was K-ras-2
      point mutation (58%), 3p25-26 and 17q21 (35%), 5q23 (33%), 1p36 (28%), followed
      by the remaining molecular markers. The descending frequency of mutational
      content in bile duct cytology was 17p13, 1p36, 3p25-26, and 5q23 followed by
      remaining molecular markers. K-ras-2 point mutation was not seen in bile duct
      specimens. While there was overlap in the spectrum of mutational markers in
      pancreatic duct and biliary brushing cytology, the temporal profile was
      significantly different (P<0.001). Pancreatic and biliary neoplasia progression
      involves distinct subset of accumulated defined mutations. Determination of
      timing of the mutational damage in cytologic material could be incorporated in
      the work-up and help in making a more definitive diagnosis of malignancy in
      pancreatobiliary cytology specimens.

PMID- 16648876
TI  - Rescuing the NIH: the response.
AB  - The feedback received regarding my recent editorial "Rescuing the NIH before it
      is too late" has been fascinating to read. The opinions expressed illustrate a
      huge divide between those in charge of the NIH and those who rely on extramural
      funding to support their research.

PMID- 16648877
TI  - Response to: "Rescuing the NIH before it is too late".
AB  - We, the directors of the 27 NIH institutes and centers, wanted to respond to the
      points made by Andrew Marks in his recent editorial. While we appreciate that the
      scientific community has concerns, the current initiatives and directions of the
      NIH have been developed through planning processes that reflect openness and
      continued constituency input, all aimed at assessing scientific opportunities and
      addressing public health needs.

PMID- 16648878
TI  - Planning science (a generation after Lewis Thomas).
AB  - Andrew Marks' recent editorial eloquently reiterated a concern that many of us
      have voiced before, that the current policies and practices of the NIH are not
      serving the public well.

PMID- 16648879
TI  - Determination of the biotin content of select foods using accurate and sensitive
      HPLC/avidin binding.
AB  - Assessing dietary biotin content, biotin bioavailability, and resulting biotin
      status are crucial in determining whether biotin deficiency is teratogenic in
      humans. Accuracy in estimating dietary biotin is limited both by data gaps in
      food composition tables and by inaccuracies in published data. The present study
      applied sensitive and specific analytical techniques to determine values for
      biotin content in a select group of foods. Total biotin content of 87 foods was
      determined using acid hydrolysis and the HPLC/avidin-binding assay. These values
      are consistent with published values in that meat, fish, poultry, egg, dairy, and
      some vegetables are relatively rich sources of biotin. However, these biotin
      values disagreed substantially with published values for many foods. Assay values
      varied between 247 times greater than published values for a given food to as
      much as 36% less than the published biotin value. Among 51 foods assayed for
      which published values were available, only seven agreed within analytical
      variability (720%). We conclude that published values for biotin content of foods
      are likely to be inaccurate.

PMID- 16648880
TI  - Neural foundations for understanding social and mechanical concepts.
AB  - Motivated by neuropsychological investigations of category-specific impairments,
      many functional brain imaging studies have found distinct patterns of neural
      activity associated with different object categories. However, the extent to
      which these category-related activation patterns reflect differences in
      conceptual representation remains controversial. To investigate this issue,
      functional magnetic resonance imaging (fMRI) was used to record changes in neural
      activity while subjects interpreted animated vignettes composed of simple
      geometric shapes in motion. Vignettes interpreted as conveying social
      interactions elicited a distinct and distributed pattern of neural activity,
      relative to vignettes interpreted as mechanical actions. This neural system
      included regions in posterior temporal cortex associated with identifying human
      faces and other biological objects. In contrast, vignettes interpreted as
      conveying mechanical actions resulted in activity in posterior temporal lobe
      sites associated with identifying manipulable objects such as tools. Moreover,
      social, but not mechanical, interpretations elicited activity in regions
      implicated in the perception and modulation of emotion (right amygdala and
      ventromedial prefrontal cortex). Perceiving and understanding social and
      mechanical concepts depends, in part, on activity in distinct neural networks.
      Within the social domain, the network includes regions involved in processing and
      storing information about the form and motion of biological objects, and in
      perceiving, expressing, and regulating affective responses.

PMID- 16648881
TI  - Making the most of a patient's laboratory data: optimisation of signal-to-noise
      ratio.
AB  - All results in laboratory medicine are compared to some reference for
      interpretation. This reference may be a previous result from the same patient, a
      reference population--either healthy or diseased, or both--or a decision limit
      recommended by an expert group. The aim for the medical laboratory is to improve
      the signal-to-noise ratio by increasing the signal or reducing the noise. This
      presentation deals with the more general tools for reduction of the noise
      component, and focuses on biological within-subject variation, reference
      intervals and decision models. Regarding biological within-subject variation, the
      estimation of reference change value (RCV) as a yardstick for judging measured
      differences within the patient over time is an important tool. Here, only type 1
      errors are usually applied, but type 2 errors should also be taken into
      consideration. Moreover, variance homogeneity is assumed for the application of
      RCV, but this assumption is not always fulfilled, and erroneous interpretations
      may be introduced. A tool for comparison of different and more complicated
      algorithms applied to serial measurements is computer simulation (e.g. on data
      from tumour markers). In order to reduce the noise component from reference
      intervals, partitioning according to relevant subgroups is a tool, and useful
      criteria for judging whether subgroups should be combined are reported.
      Geographical and racial differences may cause different reference distributions
      (e.g. plasma proteins), but it has been possible to establish common reference
      intervals for 25 common components in Caucasians in the five Nordic countries.
      Transformation of data and presentation of accumulated ranked values in rankit
      plots where Gaussian (or log-Gaussian) distributions show up as straight lines is
      a valuable tool for interpretation of the distributions and comparison of
      subgroups. In this way it is often possible to isolate a low-risk group which
      fits a log-Gaussian distribution. In case of thyroid autoantibodies the
      distributions look biphasic, even after all possible rule-out criteria have been
      exhausted, but a composite model makes it possible to extract a reference
      population from the mixture. The classical decision model is bimodal, reflecting
      an assumption of two independent but overlapping distributions, with a clear but
      unknown prevalence for the disease. When a decision limit (cut-off point) is
      applied, the percentages of false positive and false negative results will be
      determined, but the underlying prevalence is unchanged. In contrast to this, the
      unimodal distributions cover a continuum of probabilities for a certain disease
      (risk) and the decision limit is arbitrarily chosen. Thus, the disease or risk is
      defined by the measured component. Consequently, the decision limit directly
      defines the prevalence, and this limit can be different over time and geography
      as has been the case for cholesterol or glucose.

PMID- 16648882
TI  - Biochemical markers of bone turnover: part I: biochemistry and variability.
AB  - With the ageing population in most countries, disorders of bone and mineral
      metabolism are becoming increasingly relevant to every day clinical practice.
      Consequently, the interest in, and the need for effective measures to be used in
      the screening, diagnosis and follow-up of such pathologies has markedly grown.
      Together with clinical and imaging techniques, biochemical tests play an
      important role in the assessment and differential diagnosis of metabolic bone
      disease. In recent years, the isolation and characterisation of cellular and
      extracellular components of the skeletal matrix have resulted in the development
      of molecular markers that are considered to reflect either bone formation or bone
      resorption. These biochemical indices are non-invasive, comparatively inexpensive
      and, when applied and interpreted correctly, helpful tools in the diagnostic and
      therapeutic assessment of metabolic bone disease. Part I of this article provides
      an overview of the basic biochemistry of bone markers, and sources of non
      specific variability. Part II (to be published in a subsequent issue of this
      journal) will review the current evidence regarding the clinical use of
      biochemical markers of bone remodelling in metabolic and metastatic bone disease.

PMID- 16648883
TI  - Below the radar: advanced glycation end products that detour "around the side".
      Is HbA1c not an accurate enough predictor of long term progression and glycaemic
      control in diabetes?
AB  - Advanced glycation is the irreversible attachment of reducing sugars onto the
      free amino groups of proteins. Its physiological roles are thought to include the
      identification of senescent proteins and hence there is a time dependent
      accumulation of advanced glycation end products (AGEs). AGE labelled proteins are
      catabolised by cells into low molecular weight peptides and amino acids and
      excreted primarily via the kidneys. This process appears to be tightly controlled
      by AGE clearance receptor complexes containing AGE-R1, AGE-R2 and AGE-R3 and
      scavenger receptors such as CD36, SR-AII and SR-BI. Conditions such as diabetes,
      however, which have a metabolic overload of reducing sugars, rapidly accelerate
      AGE formation. In addition, advanced glycation is facilitated by oxidative stress
      and renal disease even in the absence of increases in reducing sugar
      concentrations. As part of our western diet, we also ingest AGEs of which
      approximately 50-80% are absorbed, catabolised and excreted over a period of two
      days. As AGE levels rise during diabetes, interruption of normal function occurs
      via three distinct mechanisms, namely AGE induced cross-linking of extracellular
      matrices, stiffening elastic fibres, disturbing cellular adhesion and preventing
      turnover. The second is by intracellular formation of AGEs, which causes
      generalised cellular dysfunction. The third is via the chronic activation of
      specific receptors such as RAGE, the receptor for advanced glycation end
      products, which produces excesses in inflammatory molecule production. Due to the
      range of dysfunction produced by the accumulation of AGEs in diabetes, there is a
      growing need for early recognition and intervention in this process.

PMID- 16648885
TI  - Uncertainty of measurement: what it is and what it should be.

PMID- 16648884
TI  - The relevance of sweat testing for the diagnosis of cystic fibrosis in the
      genomic era.
AB  - Cystic fibrosis (CF) is the most common inherited disorder of childhood. The
      diagnosis of CF has traditionally been based on clinical features with
      confirmatory evidence by sweat electrolyte analysis. Since 1989 it has been
      possible to also use gene mutation analysis to aid the diagnosis. Cloning of the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene has advanced our
      understanding of CF, in particular the molecular basis of an expanded CF
      phenotype. However, because there are over 1000 mutations and 200 polymorphisms,
      many without recognised effects on CFTR, the molecular diagnosis can be
      troublesome. This has necessitated measurement of CFTR function with renewed
      interest in the sweat test. This review provides an overview of the clinical
      features of CF, the diagnosis and complex genetics. We provide a detailed
      discussion of the structure and function of CFTR and the classification of CFTR
      mutations. Sweat electrolyte analysis is discussed, from the physiology of
      sweating to the rigours of a properly performed sweat test and its
      interpretation. With this information it is possible to understand the relevance
      of the sweat test in the genomic era.

PMID- 16648887
TI  - Radiographic imaging of the distal dural ring for determining the intradural or
      extradural location of aneurysms.
AB  - The effectiveness of several anatomical and radiological landmarks proposed to
      determine whether an aneurysm is located intradurally or extradurally is still
      debated. In anatomical and radiological studies, we examined the relationships of
      the distal dural ring (DDR) to the internal carotid artery (ICA) and surrounding
      bony structures to aid in the localization of aneurysms near the DDR. Anatomical
      relationships were examined by performing dissections on 10 specimens (5 formalin
      fixed cadaveric heads). After the position of the DDR, optic nerve, and
      tuberculum sellae were marked with surgical steel wire, radiographs were taken in
      multiple projections. The only bony landmark consistently visible on radiographs
      was the planum sphenoidale. The superior border of the DDR is located at or below
      the level of the tuberculum sellae, which laterally becomes the superomedial
      aspect of the optic strut; thus, the optic strut marks the dorsal limit of the
      DDR. On 50 dry skulls, we measured the vertical distance between the planum
      sphenoidale and medial aspect of the optic strut (5.0 +/- 0.4 mm), the interoptic
      strut distance (14.4 +/- 1.4 mm), and the linear distance between the most
      posterior aspect of the planum sphenoidale (limbus sphenoidale) and the
      tuberculum sellae (6.0 +/- 0.5 mm). Using these measurements and the planum
      sphenoidale, tuberculum sellae, and optic strut as reference landmarks, we
      determined the location of the aneurysm relative to the DDR on angiographic
      images. In this way, we were able to identify whether lesions were intra- or
      extradural.

PMID- 16648888
TI  - Clinicoradiological and surgical considerations in the treatment of cholesterol
      granuloma of the petrous pyramid.
AB  - We describe a 71-year-old woman who complained of a 1-year history of double
      vision when looking to the left, numbness over the right cheek, intermittent
      tinnitus, and gradually increasing unsteadiness when walking. Computed tomography
      and magnetic resonance imaging revealed a cholesterol granuloma at the right
      pyramidal apex anterior to the internal auditory canal and a slight compression
      of the brainstem on the ipsilateral side. For surgical removal we used the
      transtemporal approach instead of the trans-sphenoidal approach to obtain better
      control over the internal carotid artery. To avoid the problems of stenting, the
      resulting dead space was obliterated with fat. We discuss the essential
      preoperative imaging, controversies in choosing the appropriate surgical
      approach, and developments in treatment.

PMID- 16648889
TI  - Ameloblastic carcinoma arising from anterior skull base.
AB  - Ameloblastic carcinoma (AC) is an aggressive malignant epithelial odontogenic
      tumor. It may appear de novo or originate from a pre-existing ameloblastoma or
      odontogenic cyst. To our knowledge, an AC that originates from the anterior skull
      base has not been reported before in the English literature. We report a case of
      an AC that originated from the anterior skull base and invaded the dura of the
      anterior fossa and discuss its clinical course and treatment.

PMID- 16648890
TI  - Aggressive syringomatous carcinoma of the orbit.
AB  - A 68-year-old woman with an unusual tumor involving the right orbit presented
      with painful exophthalmos of the right eye. Excision biopsy of her right eyelid
      was performed. The specimen showed ductal differentiation with comma-like
      extensions identical to syringoma. Cellular atypia, an invasive growth pattern,
      and remarkable perineural invasion led to the diagnosis of syringomatous
      carcinoma. Magnetic resonance imaging showed that the tumor exhibited maxillary
      involvement, invading the supraorbital fissure and bone of the middle skull base.
      The patient underwent craniofacial resection and has been alive with no sign of
      recurrence for 2 years. This case suggests that wide excision of these tumors
      with a clear surgical margin using skull base surgical techniques may offer a
      good prognosis.

PMID- 16648891
TI  - Carcinoma of the breast metastatic to the optic nerve mimicking an optic nerve
      sheath meningioma: case report and review of the literature.
AB  - Isolated metastatic tumors to the optic nerve are extremely rare. We describe a
      rare and unusual case of metastatic breast carcinoma to the optic nerve that
      mimicked an optic nerve sheath meningioma in its presentation due to its indolent
      symptom progression, initial radiological appearance, and minimal growth on
      serial imaging. The patient, a 46-year-old woman with a history of stable
      metastatic breast carcinoma, presented with progressive visual loss in her right
      eye over a 6-month interval. Magnetic resonance imaging revealed an enhancing
      lesion in the optic canal with an extension to the right anterior clinoid process
      and planum sphenoidale and into the right orbital apex, consistent with the
      presumptive diagnosis of optic nerve sheath meningioma. The tumor was resected
      and pathologically confirmed to be metastatic carcinoma of the breast. The
      clinical course, radiological features, surgical approach, and treatment
      strategies are reviewed.

PMID- 16648892
TI  - The importance of the Thr17 residue of phospholamban as a phosphorylation site
      under physiological and pathological conditions.
AB  - The sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) is under the control of an
      SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a,
      whereas phosphorylation of PLN at either the Ser16 site by PKA or the Thr17 site
      by CaMKII reverses this inhibition, thus increasing SERCA2a activity and the rate
      of Ca2+ uptake by the SR. This leads to an increase in the velocity of
      relaxation, SR Ca2+ load and myocardial contractility. In the intact heart, beta
      adrenoceptor stimulation results in phosphorylation of PLN at both Ser16 and
      Thr17 residues. Phosphorylation of the Thr17 residue requires both stimulation of
      the CaMKII signaling pathways and inhibition of PP1, the major phosphatase that
      dephosphorylates PLN. These two prerequisites appear to be fulfilled by beta
      adrenoceptor stimulation, which as a result of PKA activation, triggers the
      activation of CaMKII by increasing intracellular Ca2+, and inhibits PP1. Several
      pathological situations such as ischemia-reperfusion injury or hypercapnic
      acidosis provide the required conditions for the phosphorylation of the Thr17
      residue of PLN, independently of the increase in PKA activity, i.e., increased
      intracellular Ca2+ and acidosis-induced phosphatase inhibition. Our results
      indicated that PLN was phosphorylated at Thr17 at the onset of reflow and
      immediately after hypercapnia was established, and that this phosphorylation
      contributes to the mechanical recovery after both the ischemic and acidic
      insults. Studies on transgenic mice with Thr17 mutated to Ala (PLN-T17A) are
      consistent with these results. Thus, phosphorylation of the Thr17 residue of PLN
      probably participates in a protective mechanism that favors Ca2+ handling and
      limits intracellular Ca2+ overload in pathological situations.

PMID- 16648893
TI  - Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil.
AB  - Kaposi's sarcoma (KS) became a critical health issue with the emergence of
      acquired immunodeficiency syndrome (AIDS) in the 1980s. Four clinical
      epidemiological forms of KS have been described: classical KS, endemic KS,
      iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated
      herpesvirus (KSHV) or human herpesvirus type 8 was identified by Chang and
      colleagues, and has been detected worldwide at frequencies ranging from 80 to
      100%. The aim of the present study was to evaluate the frequency of KSHV
      infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as
      well as to review the current knowledge about KS transmission and detection. For
      these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2%) cases of
      classical KS, 29 (56.9%) of AIDS-associated KS and 2 (3.9%) of iatrogenic KS.
      Most patients were males (7.5:1, M/F), and mean age was 47.9 years (SD = +/- 18.7
      years). As expected, HIV-positive KS patients were younger than patients with
      classical KS. On the other hand, patients with AIDS-associated KS have early
      lesions (patch and plaque) compared to classical KS patients (predominantly
      nodular lesions). This is assumed to be the result of the early diagnose of KS in
      the HIV-positive setting. KSHV infection was detected by PCR in almost all cases
      (48/51; 94.1%), irrespectively of the clinical-epidemiological form of KS. These
      results show that KSHV is associated with all forms of KS in Brazilian patients,
      a fact that supports the role of this virus in KS pathogenesis.

PMID- 16648894
TI  - Effect of psychological stress on the L-arginine-nitric oxide pathway and semen
      quality.
AB  - It has been reported that mental stress causes abnormality of spermiogram
      parameters. We investigated the effect of psychological stress on the L-arginine
      nitric oxide (NO) pathway. Semen samples were collected from 29 healthy fourth
      semester medical students just before (stress) and 3 months after (non-stress)
      the final examinations. Psychological stress was measured by the State Anxiety
      Inventory questionnaire. After standard semen analysis, arginase activity and NO
      concentration were measured spectrophotometrically in the seminal plasma.
      Measurements were made in duplicate. During the stress period, sperm
      concentration (41.28 +/- 3.70 vs 77.62 +/- 7.13 x 10(6)/mL), rapid progressive
      motility of spermatozoa (8.79 +/- 1.66 vs 20.86 +/- 1.63%) and seminal plasma
      arginase activity (0.12 +/- 0.01 vs 0.22 +/- 0.01 U/mL) were significantly lower
      than in the non-stress situation, whereas seminal plasma NO (17.28 +/- 0.56 vs
      10.02 +/- 0.49 micromol/L) was higher compared to the non-stress period (P <
      0.001 for all). During stress there was a negative correlation between NO
      concentration and sperm concentration, the percentage of rapid progressive
      motility and arginase activity (r = -0.622, P < 0.01; r = -0.425, P < 0.05 and r
      = -0.445, P < 0.05, respectively). These results indicate that psychological
      stress causes an increase of NO level and a decrease of arginase activity in the
      L-arginine-NO pathway. Furthermore, poor sperm quality may be due to excessive
      production of NO under psychological stress. In the light of these results, we
      suggest that the arginine-NO pathway, together with arginase and NO synthase, are
      involved in semen quality under stress conditions.

PMID- 16648895
TI  - Rapid, reliable and inexpensive quality assessment of biotinylated cRNA.
AB  - The interpretation of oligonucleotide array experiments depends on the quality of
      the target cRNA used. cRNA target quality is assessed by quantitative analysis of
      the representation of 5' and 3' sequences of control genes using commercially
      available Test arrays. The Test array provides an economically priced means of
      determining the quality of labeled target prior to analysis on whole genome
      expression arrays. This manuscript validates the use of a duplex RT-PCR assay as
      a faster (6 h) and less expensive (<10 US dollars) but equally accurate
      alternative to the Test arrays in determining biotinylated cRNA quality. Forty
      one different cRNA samples were hybridized to HG-U133A microarrays from
      Affymetrix. Ten cRNA samples with a beta-actin 3'/5' ratio >6 were chosen and
      classified as degraded cRNAs, and 31 samples with a beta-actin 3'/5' ratio <6
      were selected as good quality cRNAs. Blinded samples were then used for the RT
      PCR assay. After gel electrophoresis, optical densities of the amplified 3' and
      5' fragments of beta-actin were measured and the 3'/5' ratio was calculated.
      There was a strong correlation (r(2) = 0.6802) between the array and the RT-PCR
      beta-actin 3'/5' ratios. Moreover, the RT-PCR 3'/5' ratio was significantly
      different (P < 0.0001) between undegraded (mean +/- SD, 0.34 +/- 0.09) and
      degraded (1.71 +/- 0.83) samples. None of the other parameters analyzed, such as
      i) the starting amount of RNA, ii) RNA quality assessed using the Bioanalyzer
      Chip technology, or iii) the concentration and OD260/OD280 ratio of the purified
      biotinylated cRNA, correlated with cRNA quality.

PMID- 16648896
TI  - Prevalence of hepatitis C virus (HCV) infection and HCV genotypes of hemodialysis
      patients in Salvador, Northeastern Brazil.
AB  - Hepatitis C virus (HCV) infection has been identified as the major cause of
      chronic liver disease among patients on chronic hemodialysis (HD), despite the
      important reduction in risks obtained by testing candidate blood donors for anti
      HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross
      sectional study was performed to estimate the prevalence of HCV infection and
      genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV
      seroprevalence was determined by ELISA in 1243 HD patients from all ten different
      dialysis centers of the city. HCV infection was confirmed by RT-PCR and
      genotyping was performed by restriction fragment length polymorphism. Anti-HCV
      seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3) (Murex anti-HCV,
      Abbott Murex, Chicago, IL, USA). Blood samples for qualitative HCV detection and
      genotyping were collected from 125/130 seropositive HD patients (96.2%). HCV-RNA
      was detected in 92/125 (73.6%) of the anti-HCV-positive patients. HCV genotype 1
      (77.9%) was the most prevalent, followed by genotype 3 (10.5%) and genotype 2
      (4.6%). Mixed infections of genotypes 1 and 3 were found in 7.0% of the total
      number of patients. The present results indicate a significant decrease in anti
      HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the
      present study. The HCV genotype distribution was closely similar to that observed
      in other hemodialysis populations in Brazil, in local candidate blood donors and
      in other groups at risk of transfusion-transmitted infection.

PMID- 16648897
TI  - Contribution of matrix vesicles and alkaline phosphatase to ectopic bone
      formation.
AB  - Endochondral calcification involves the participation of matrix vesicles (MVs),
      but it remains unclear whether calcification ectopically induced by implants of
      demineralized bone matrix also proceeds via MVs. Ectopic bone formation was
      induced by implanting rat demineralized diaphyseal bone matrix into the dorsal
      subcutaneous tissue of Wistar rats and was examined histologically and
      biochemically. Budding of MVs from chondrocytes was observed to serve as
      nucleation sites for mineralization during induced ectopic osteogenesis,
      presenting a diameter with Gaussian distribution with a median of 306 +/- 103 nm.
      While the role of tissue-nonspecific alkaline phosphatase (TNAP) during
      mineralization involves hydrolysis of inorganic pyrophosphate (PPi), it is
      unclear how the microenvironment of MV may affect the ability of TNAP to
      hydrolyze the variety of substrates present at sites of mineralization. We show
      that the implants contain high levels of TNAP capable of hydrolyzing p
      nitrophenylphosphate (pNPP), ATP and PPi. The catalytic properties of glycosyl
      phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol
      specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as
      substrates. While the enzymatic efficiency (k cat/Km) remained comparable between
      polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k
      cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme
      increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi,
      respectively, compared to the membrane-bound enzyme. Our data are consistent with
      the involvement of MVs during ectopic calcification and also suggest that the
      location of TNAP on the membrane of MVs may play a role in determining substrate
      selectivity in this micro-compartment.

PMID- 16648898
TI  - Erythrocyte glucose-6-phosphate dehydrogenase from Brazilian opossum Didelphis
      marsupialis.
AB  - In a comparative study of erythrocyte metabolism of vertebrates, the specific
      activity of glucose-6-phosphate dehydrogenase (G6PD) of the Brazilian opossum
      Didelphis marsupialis in a hemolysate was shown to be high, 207 +/- 38 IU g-1 Hb
      1 min-1 at 37 degrees C, compared to the human erythrocyte activity of 12 +/- 2
      IU g-1 Hb-1 min-1 at 37 degrees C. The apparent high specific activity of the
      mixture led us to investigate the physicochemical properties of the opossum
      enzyme. We report that reduced glutathione (GSH) in the erythrocytes was only 50%
      higher than in human erythrocytes, a value lower than expected from the high G6PD
      activity since GSH is maintained in a reduced state by G6PD activity. The
      molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was
      265 kDa, which is essentially the same as that of human G6PD (260 kDa). The
      Michaelis-Menten constants (Km: 55 microM) for glucose-6-phosphate and
      nicotinamide adenine dinucleotide phosphate (Km: 3.3 microM) were similar to
      those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively). A 450-fold
      purification of the opossum enzyme was achieved and the specific activity of the
      purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein
      observed for human G6PD. We conclude that G6PD after purification from the
      hemolysate of D. marsupialis does not have a high specific activity. Thus, it is
      quite probable that the red cell hyperactivity reported may be explained by
      increased synthesis of G6PD molecules per unit of hemoglobin or to reduced
      inactivation in the RBC hemolysate.

PMID- 16648899
TI  - Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha
      transgenic mouse model.
AB  - Acute promyelocytic leukemia (APL) is characterized by the expansion of blasts
      that resemble morphologically promyelocytes and harbor a chromosomal
      translocation involving the retinoic acid receptor alpha (RARalpha) and the
      promyelocytic leukemia (PML) genes on chromosomes 17 and 15, respectively. The
      expression of the PML/RARalpha fusion gene is essential for APL genesis. In fact,
      transgenic mice (TM) expressing PML/RARalpha develop a form of leukemia that
      mimics the hematological findings of human APL. Leukemia is diagnosed after a
      long latency (approximately 12 months) during which no hematological abnormality
      is detected in peripheral blood (pre-leukemic phase). In humans, immunophenotypic
      analysis of APL blasts revealed distinct features; however, the precise
      immunophenotype of leukemic cells in the TM model has not been established. Our
      aim was to characterize the expression of myeloid antigens by leukemic cells from
      hCG-PML/RARalpha TM. In this study, TM (N = 12) developed leukemia at the mean
      age of 13.1 months. Morphological analysis of bone marrow revealed an increase of
      the percentage of immature myeloid cells in leukemic TM compared to pre-leukemic
      TM and wild-type controls (48.63 +/- 16.68, 10.83 +/- 8.11, 7.4 +/- 5.46%,
      respectively; P < 0.05). Flow cytometry analysis of bone marrow and spleen from
      leukemic TM identified the asynchronous co-expression of CD34, CD117, and CD11b.
      This abnormal phenotype was rarely detected prior to the diagnosis of leukemia
      and was present at similar frequencies in hematologically normal TM and wild-type
      controls of different ages. The present results demonstrate that, similarly to
      human APL, leukemic cells from hCG-PML/RARalpha TM present a specific
      immunophenotype.

PMID- 16648900
TI  - Early remodeling of rat cardiac muscle induced by swimming training.
AB  - The aim of the present investigation was to study the effect of acute swimming
      training with an anaerobic component on matrix metallopeptidase (MMP) activity
      and myosin heavy chain gene expression in the rat myocardium. Animals (male
      Wistar rats, weighing approximately 180 g) were trained for 6 h/day in 3 sessions
      of 2 h each for 1 to 5 consecutive days (N = 5 rats per group). Rats swam in
      basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35 degrees C.
      After the training period a significant increase (P < 0.05) was observed in the
      heart weight normalized to body weight by about 22 and 35% in the groups that
      trained for 96 and 120 h, respectively. Blood lactate levels were significantly
      increased (P < 0.05) in all groups after all training sessions, confirming an
      anaerobic component. However, lactate levels decreased (P < 0.05) with days of
      training, suggesting that the animals became adapted to this protocol. Myosin
      heavy chain-beta gene expression, analyzed by real time PCR and normalized with
      GAPDH gene expression, showed a significant two-fold increase (P < 0.01) after 5
      days of training. Zymography analysis of myocardium extracts indicated a single
      approximately 60-kDa activity band that was significantly increased (P < 0.05)
      after 72, 96, and 120 h, indicating an increased expression of MMP-2 and
      suggesting precocious remodeling. Furthermore, the presence of MMP-2 was
      confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3.
      Taken together, our results indicate that in these training conditions, the rat
      heart undergoes early biochemical and functional changes required for the
      adaptation to the new physiological condition by tissue remodeling.

PMID- 16648901
TI  - Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice
      and on atherogenesis in apolipoprotein E knock-out mice.
AB  - Elevated blood cholesterol is an important risk factor associated with
      atherosclerosis and coronary heart disease. Several studies have reported a
      decrease in serum cholesterol during the consumption of large doses of fermented
      dairy products or lactobacillus strains. The proposed mechanism for this effect
      is the removal or assimilation of intestinal cholesterol by the bacteria,
      reducing cholesterol absorption. Although this effect was demonstrated in vitro,
      its relevance in vivo is still controversial. Furthermore, few studies have
      investigated the role of lactobacilli in atherogenesis. The aim of the present
      study was to determine the effect of Lactobacillus delbrueckii on cholesterol
      metabolism in germ-free mice and the possible hypocholesterolemic and
      antiatherogenic action of these bacteria using atherosclerosis-prone
      apolipoprotein E (apo E) knock-out (KO) mice. For this purpose, Swiss/NIH germ
      free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic
      diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and
      treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol
      excretion in germ-free mice, which was not associated with changes in blood or
      liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii
      was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in
      the aorta was also similar in mice receiving or not these bacteria. In
      conclusion, these results suggest that, although L. delbrueckii treatment was
      able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or
      antiatherogenic effect was observed in apo E KO mice.

PMID- 16648902
TI  - Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide
      injection in the brainstem of Wistar rats submitted to streptozotocin
      diabetogenic treatment.
AB  - Schwann cell disturbance followed by segmental demyelination in the peripheral
      nervous system occurs in diabetic patients. Since Schwann cell and
      oligodendrocyte remyelination in the central nervous system is a well-known event
      in the ethidium bromide (EB) demyelinating model, the aim of this investigation
      was to determine the behavior of both cell types after local EB injection into
      the brainstem of streptozotocin diabetic rats. Adult male Wistar rats received a
      single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10
      days later to a single injection of 10 microL 0.1% (w/v) EB or 0.9% saline
      solution into the cisterna pontis. Ten microliters of 0.1% EB was also injected
      into non-diabetic rats. The animals were anesthetized and perfused through the
      heart 7 to 31 days after EB or saline injection and brainstem sections were
      collected and processed for light and transmission electron microscopy. The final
      balance of myelin repair in diabetic and non-diabetic rats at 31 days was
      compared using a semi-quantitative method. Diabetic rats presented delayed
      macrophage activity and lesser remyelination compared to non-diabetic rats.
      Although oligodendrocytes were the major remyelinating cells in the brainstem,
      Schwann cells invaded EB-induced lesions, first appearing at 11 days in non
      diabetic rats and by 15 days in diabetic rats. Results indicate that short-term
      streptozotocin-induced diabetes hindered both oligodendrocyte and Schwann cell
      remyelination (mean remyelination scores of 2.57 +/- 0.77 for oligodendrocytes
      and 0.67 +/- 0.5 for Schwann cells) compared to non-diabetic rats (3.27 +/- 0.85
      and 1.38 +/- 0.81, respectively).

PMID- 16648903
TI  - Contested dominance modifies the anovulatory consequences of social subordination
      in female marmosets.
AB  - Dominance status among female marmosets is reflected in agonistic behavior and
      ovarian function. Socially dominant females receive submissive behavior from
      subordinates, while exhibiting normal ovulatory function. Subordinate females,
      however, receive agonistic behavior from dominants, while exhibiting reduced or
      absent ovulatory function. Such disparity in female fertility is not absolute,
      and groups with two breeding females have been described. The data reported here
      were obtained from 8 female-female pairs of captive female marmosets, each housed
      with a single unrelated male. Pairs were classified into two groups:
      "uncontested" dominance (UD) and "contested" dominance (CD), with 4 pairs each.
      Dominant females in UD pairs showed significantly higher frequencies (4.1) of
      agonism (piloerection, attack and chasing) than their subordinates (0.36), and
      agonistic behaviors were overall more frequently displayed by CD than by UD
      pairs. Subordinates in CD pairs exhibited more agonistic behavior (2.9) than
      subordinates in UD pairs (0.36), which displayed significantly more submissive
      (6.97) behaviors than their dominants (0.35). The data suggest that there is more
      than one kind of dominance relationship between female common marmosets.
      Assessment of progesterone levels showed that while subordinates in UD pairs
      appeared to be anovulatory, the degree of ovulatory disruption in subordinates of
      CD pairs was more varied and less complete. We suggest that such variation in
      female-female social dominance relationships and the associated variation in the
      degree and reliability of fertility suppression may explain variations of the
      reproductive condition of free-living groups of common marmosets.

PMID- 16648904
TI  - Gender-related pathways for behavior problems in the offspring of alcoholic
      fathers.
AB  - The objective of the present study was to examine gender differences in the
      influence of paternal alcoholism on children's social-emotional development and
      to determine whether paternal alcoholism is associated with a greater number of
      externalizing symptoms in the male offspring. From the Mannheim Study of Risk
      Children, an ongoing longitudinal study of a high-risk population, the
      developmental data of 219 children [193 (95 boys and 98 girls) of non-alcoholic
      fathers, non-COAs, and 26 (14 boys, 12 girls) of alcoholic fathers, COAs] were
      analyzed from birth to the age of 11 years. Paternal alcoholism was defined
      according to the ICD-10 categories of alcohol dependence and harmful use. Socio
      demographic data, cognitive development, number and severity of behavior
      problems, and gender-related differences in the rates of externalizing and
      internalizing symptoms were assessed using standardized instruments (IQ tests,
      Child Behavior Checklist questionnaire and diagnostic interviews). The general
      linear model analysis revealed a significant overall effect of paternal
      alcoholism on the number of child psychiatric problems (F = 21.872, d.f. = 1.217,
      P < 0.001). Beginning at age 2, significantly higher numbers of externalizing
      symptoms were observed among COAs. In female COAs, a pattern similar to that of
      the male COAs emerged, with the predominance of delinquent and aggressive
      behavior. Unlike male COAs, females showed an increase of internalizing symptoms
      up to age 11 years. Of these, somatic complaints revealed the strongest
      discriminating effect in 11-year-old females. Children of alcoholic fathers are
      at high risk for psychopathology. Gender-related differences seem to exist and
      may contribute to different phenotypes during development from early childhood to
      adolescence.

PMID- 16648905
TI  - Evidence for the participation of nitric oxide in pemphigus.
AB  - Pemphigus is an inflammatory autoimmune disorder of the skin. Nitric oxide (NO)
      is an inflammatory mediator linked to a variety of physiological and
      pathophysiological phenomena that include skin tumors, psoriasis, urticaria, and
      atopic dermatitis. Inflammatory cells present in pemphigus lesions are important
      sources of NO production. We investigated whether NO is involved in pemphigus. A
      prospective cohort study was conducted at the Dermatology Service of the Hospital
      Universitario Walter Cantidio of the Federal University of Ceara. All patients
      seen at the outpatient clinic between August 2000 and July 2001, with a
      clinically and histologically confirmed diagnosis of pemphigus were included. The
      median age was 42.5 years (range: 12-69 years) with a male to female ratio of
      3:2. Total serum nitrite levels, used as a marker for NO production, were
      determined by the Griess reaction. Skin biopsies from pemphigus and breast
      surgery (control) patients were used for the detection of the inducible NO
      synthase (iNOS) by immunohistochemistry. Twenty-two (22) patients with pemphigus
      and eight (8) controls who did not differ in demographic characteristics were
      included. Total serum nitrite levels were significantly higher (>7 micromol/L) in
      pemphigus patients compared to controls (<6 micromol/L), regardless of the
      severity of the clinical activity of pemphigus (P < 0.0001). All pemphigus
      biopsies presented increased immunostaining for iNOS that was not detected in
      normal skin samples. These data are the first to demonstrate that pemphigus
      patients display increased serum NO levels that are associated with increased
      iNOS expression in the affected skin.

PMID- 16648906
TI  - Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal
      carcinoma cells in vitro.
AB  - Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in
      close association with Epstein-Barr virus-encoded latent membrane protein 1
      (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and
      differentiation in NPC xenografts. Then, can it repress the cancer cells'
      metastasis potential? To elucidate this issue, the present study was performed.
      LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as
      in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3
      for 48 h. Then the survival cells were collected to investigate their potential
      of colony formation, attachment, invasion, and migration. Both confocal
      immunofluorescence staining and Western blot were used to detect the changes of
      LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western
      blot. The results were as follow: i) the colony formation inhibition rate (75.41
      +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of
      attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion
      inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the
      migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%)
      were all significantly different between the two cell lines (P < 0.01). ii) LMP1
      was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9
      was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we
      conclude that As2O3 can reduce metastasis potential of NPC cells, involving
      inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed
      to enhance anti-metastasis activity of As2O3.

PMID- 16648907
TI  - Performance of two-dimensional Doppler echocardiography for the assessment of
      infarct size and left ventricular function in rats.
AB  - Although echocardiography has been used in rats, few studies have determined its
      efficacy for estimating myocardial infarct size. Our objective was to estimate
      the myocardial infarct size, and to evaluate anatomic and functional variables of
      the left ventricle. Myocardial infarction was produced in 43 female Wistar rats
      by ligature of the left coronary artery. Echocardiography was performed 5 weeks
      later to measure left ventricular diameter and transverse area (mean of 3
      transverse planes), infarct size (percentage of the arc with infarct on 3
      transverse planes), systolic function by the change in fractional area, and
      diastolic function by mitral inflow parameters. The histologic measurement of
      myocardial infarction size was similar to the echocardiographic method.
      Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and
      from 5 to 69.8% when determined by echocardiography, with good correlation (r =
      0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and
      mean diastolic transverse area correlated with myocardial infarct size by
      histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged
      from 28.5 +/- 5.6 (large-size myocardial infarction) to 53.1 +/- 1.5% (control)
      and correlated with myocardial infarct size by echocardiography (r = -0.87; P <
      0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral
      inflow velocity for animals with large-size myocardial infarction (5.6 +/- 2.7)
      was significantly higher than for all others (control: 1.9 +/- 0.1; small-size
      myocardial infarction: 1.9 +/- 0.4; moderate-size myocardial infarction: 2.8 +/-
      2.3). There was good agreement between echocardiographic and histologic estimates
      of myocardial infarct size in rats.

PMID- 16648908
TI  - Transplantation: polyomavirus nephropathy and the risk of specific
      immunosuppression regimens.
AB  - BK virus is ubiquitously present in the latent state in humans, and awareness of
      the importance of BK polyomavirus is emerging among the kidney transplant
      community. First discovered in 1971 in the urine of a renal transplant recipient,
      BK virus nephropathy (BKVN) has come to be recognized as a significant cause of
      genitourinary disease and potential graft loss in the kidney transplant patient.
      In this review, we discuss the risk factors, available methods of diagnosis and
      therapeutic monitoring, and current approaches to therapy of BKVN.

PMID- 16648909
TI  - Gene array studies in renal neoplasia.
AB  - Renal cell carcinoma (RCC) is comprised of several distinct histologic subtypes
      many of which have characteristic cytogenetic abnormalities. The molecular
      pathogenesis of some of these neoplasms is beginning to be elucidated. Yet renal
      cell carcinoma is often discovered at an advanced clinical stage and effective
      pharmacologic therapies for this disease remain to be discovered. For these
      reasons, renal cell carcinoma is ideally suited to the genome scale investigation
      made possible by DNA microarrays. A number of DNA array studies of renal cell
      carcinoma have been published. Renal cell carcinomas have also been studied by
      array based comparative genomic hybridization. The purpose of this review will be
      to summarize these studies, to compare the results of the different studies, and
      to suggest future areas of investigation with a particular emphasis on clinically
      relevant advances.

PMID- 16648910
TI  - Dissecting the role of infections in atopic dermatitis.
AB  - In patients with atopic dermatitis the skin is highly susceptible to infection by
      bacteria, fungi and viruses. Increasing knowledge about the complex immune
      network that regulates anti-microbial responses has helped to dissect further the
      role of infections in atopic dermatitis. Conserved patterns of microbes are
      recognized by the innate immune system, which mediates microbicidal activity,
      either directly or through inflammatory responses. New evidence suggests that
      components of the innate immune system, such as anti-microbial peptides, humoural
      lectins, nucleotide-binding oligomerization domain-containing (NOD) proteins, and
      Toll-like receptors not only protect from microbial invasion, but contribute to
      skin inflammation in atopic dermatitis. In addition, atopic patients tend to
      develop Th2-dominated immune responses that weaken anti-microbial immunity. This
      impairment of an appropriate anti-microbial defence compounded by amplified
      microbe-driven innate and adaptive immune responses leads to the vicious circle
      of skin inflammation. New microbial management in atopic dermatitis will foster a
      well-balanced microbial flora, which establishes natural defence mechanisms to
      maintain immuno-surveillance of the skin. In addition to anti-microbial
      therapies, other innate immune stimuli may suppress pro-inflammatory signals and
      help to break the vicious circle of cutaneous inflammation. To elucidate further
      these different interactions of the skin immune system and microbes in atopic
      dermatitis, clinical studies and further efforts in basic research are needed.

PMID- 16648911
TI  - Titanium, a major constituent of blue ink, causes resistance to Nd-YAG (1064 nm)
      laser: results of animal experiments.
AB  - A blue tattoo is more resistant to laser therapy than black or brown tattoos.
      This study aimed to confirm titanium as a key response-disturbing constituent in
      a blue tattoo ink after Nd-YAG (1064 nm) laser treatment by animal experiments.
      Rabbits' backs were tattooed with four ink colours, and the Nd-YAG (1064 nm)
      laser was used to remove the tattoos. The response to the laser treatment in the
      rabbits was evaluated and electron microscopic studies were also performed.
      Excellent to fair responses were observed for the black, brown and dark brown
      inks, but the blue ink responded poorly to the laser. Histological examination
      indicated that the blue pigments were unchanged even after the laser treatment.
      Quantitative energy dispersive spectrometry revealed that blue ink contained high
      amounts of titanium. Our animal experiments confirm that a blue tattoo ink
      containing titanium, is a key element in poor response to the Nd-YAG laser.

PMID- 16648912
TI  - Isolation of ribonuclease P activity from human epidermis and its regulation by
      retinoids in vitro.
AB  - Ribonuclease P (RNase P) is a key enzyme in tRNA biogenesis that catalyses the
      endonucleolytic cleavage of tRNA precursors and generates their mature 5' ends.
      The activity of this ribozyme has never been isolated from living human tissues
      and data about epidermal tRNA biogenesis are not available. The purpose of the
      present study was to isolate and purify RNase P from human epidermis and to
      investigate the in vitro effects of retinoids on its activity. Enzyme isolation
      and purification from homogenates of keratinocytes derived after trypsinization
      from dispase-separated human epidermis were carried out using phosphocellulose
      chromatography. The optimal activity of the enzyme was found at 100 mM NH4Cl and
      5 mM MgCl2 at pH 7.5 and 37 degrees C. All-trans retinoic acid and acitretin
      revealed a dose-dependent inhibitory effect on RNase P activity. The isolation of
      RNase P activity from human epidermis, reported here for the first time, will
      enable the investigation of the possible involvement of this ribozyme in the
      regulation of epidermal differentiation and proliferation and the evaluation of
      its significance for the pathogenesis and gene therapy of various cutaneous
      disorders.

PMID- 16648913
TI  - Frequency of atopic dermatitis and relevance of food allergy in adults in
      Germany.
AB  - Many factors may aggravate atopic dermatitis. The aim of this study was to
      determine the frequency of atopic dermatitis in an unselected population sample
      and to evaluate the role of food allergy. Patients with atopic dermatitis were
      recruited from the population in Berlin, Germany, using a postal questionnaire.
      Skin prick tests for allergens were performed, followed by food challenges. A
      total of 1739 questionnaires was returned. In all, 23.5% of patients stated that
      they had atopic dermatitis, and 146 persons (8.4%) fulfilled our atopic
      dermatitis criteria after a detailed telephone interview. Of these, 111 were
      examined, and 28 (1.6%) were identified as currently suffering from atopic
      dermatitis. Twenty-seven patients were further evaluated: 9/27 were found to be
      skin prick test negative, 19/27 were skin prick test positive either to pollen
      and/or food allergens. Nine of 27 were challenged with the suspected food
      allergen: 1/9 showed a worsening of the eczema, 3/9 had oral symptoms, and 5/9
      were negative. In conclusion, only 20% of adults with a positive history of
      atopic dermatitis show active eczema lesions at a given time point. The data
      indicate that most individuals with atopic dermatitis were sensitized against
      pollen allergens and according to that, pollen-associated food allergens. A non
      selected AD patient cohort does not frequently suffer from clinically relevant
      pollen-associated food allergy.

PMID- 16648914
TI  - Asymmetry in dermoscopic melanocytic lesion images: a computer description based
      on colour distribution.
AB  - Digital dermoscopy improves the accuracy of melanoma diagnosis. The aim of this
      study was to develop and validate software for assessment of asymmetry in
      melanocytic lesion images, based on evaluation of colour symmetry, and to compare
      it with assessment by human observers. An image analysis program enabling
      numerical assessment of asymmetry in melanocytic lesions, based on the evaluation
      and comparison of CIE L*a*b* colour components (CIE L*a*b* is the name of a
      colour space defined by the Commission Internationale de l'Eclairage) inside
      image colour blocks, was employed on the recorded lesion images. Clinical
      evaluation of asymmetry in dermoscopic images was performed on the same image set
      employing a 0-1 scoring system. Asymmetry judgement was expressed by the
      clinicians for 12.8% of benign naevi, 44.7% of atypical naevi and 64.2% of
      malignant melanomas, whereas the computer identified as asymmetric 6.3%, 33.3%
      and 82.2%, respectively. Numerical parameters referring to malignant melanomas
      were significantly higher, both with respect to benign naevi and atypical naevi.
      The numerical parameters produced could be effectively employed for computer
      aided melanoma diagnosis.

PMID- 16648915
TI  - Importance of herpes simplex virus type-1 (HSV-1) in primary genital herpes.
AB  - Herpes simplex virus type 1 (HSV-1) is increasingly reported in primary genital
      herpes. Its incidence was assessed among Rotterdam sexually transmitted diseases
      clinic attendees between 1996 and 2001, and demographic and sexual behaviour
      factors were evaluated. A retrospective record analysis was performed. All herpes
      diagnoses were based on cell culture techniques. A clinical scoring system was
      used to select "primary" cases. Demographic and sexual behaviour characteristics
      were analysed using logistic regression. The clinical scoring system showed 115
      cases of primary genital herpes. HSV-1 (n = 60) was found in 52% and HSV-2 (n =
      55) in 48% of cases. The multiple logistic regression model showed that HSV-1 was
      associated with "oro-genital contact" (p < 0.001) and "having a single partner in
      the last 2 months" (p = 0.054) and that HSV-2 was associated with "a higher
      number of sexual partners in the last 6 months" (p = 0.085). Our data confirm the
      growing importance of HSV-1 in primary genital herpes; oro-genital sex is the
      main risk factor.

PMID- 16648916
TI  - Atopic dermatitis in adults: does it disappear with age?
AB  - There is limited knowledge of the prognosis in adult atopic dermatitis. We
      previously published a long-term follow-up questionnaire study of adults with
      atopic dermatitis. This study is a clinical examination of 79 adults (mean age 57
      years) recruited 3 years after that study. Most patients (68%) still reported
      that they had atopic dermatitis and 53% had ongoing eczema at examination, mainly
      located on the head and neck. Severity was mainly mild to moderate, but 12% had
      severe atopic dermatitis. IgE antibodies to Malassezia (m70) were more common in
      patients with ongoing atopic dermatitis, while positive Malassezia culture was
      seen mainly in patients with no ongoing atopic dermatitis. M. obtusa and M.
      globosa were the most commonly cultured Malassezia species. In conclusion,
      considering increased prevalence of atopic dermatitis in children in recent
      decades and the fact that atopic dermatitis in most adults continues for many
      years, we should expect to see more adults with atopic dermatitis in the future.

PMID- 16648917
TI  - Do atopics tolerate alcohol-based hand rubs? A prospective, controlled,
      randomized double-blind clinical trial.
AB  - Alcohol-based hand rubs are used frequently in healthcare settings, but their
      tolerance among atopic subjects is unknown. The dermal tolerance to five alcohol
      based hand rubs was assessed among atopic and non-atopic subjects in a repetitive
      occlusive patch test. In total, 54 subjects were analysed. One half of the
      subjects were atopic (modified Erlanger atopy score > or = 8), the other half
      were non-atopic. Treatments were controlled with water and 2% sodium dodecyl
      sulphate (SDS). Treatment sites were assessed by visual inspection (tolerability
      score 0-4). Skin redness was determined with a chromameter. The overall mean
      tolerability to all five hand rubs was lower than or identical to the negative
      control (0.02+/-0.07) and significantly different from the SDS control (0.19+/
      0.39). Skin redness was in the same range as for the negative control (0.15+/
      0.8) which was significantly lower than the SDS control (1.35+/-1.6). A
      comparison of the atopic and non-atopic subjects revealed no significant
      difference. In conclusion, we found that tolerance to the five alcohol-based hand
      rubs was good among atopic and non-atopic subjects.

PMID- 16648918
TI  - Cutaneous manifestations in patients with microscopic polyangiitis: two case
      reports and a minireview.
AB  - Microscopic polyangiitis is a systemic small vessel vasculitis, which often has
      cutaneous and musculoskeletal features. Microscopic polyangiitis is a member of
      the family of anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated
      vasculitides and is strongly associated with anti-myeloperoxidase (MPO)-ANCA.
      Titres of MPO-ANCA may reflect disease activity and play a pathogenic role.
      Patients with microscopic polyangiitis usually present with erythematous macules
      on the extremities as the first cutaneous manifestation. Skin biopsy specimens
      from the erythema reveal small-sized vessels that are infiltrated with
      neutrophils, consistent with leukocytoclastic vasculitis, in the deep dermis to
      the subcutaneous fat tissue. The cutaneous involvement is present at an early
      stage of microscopic polyangiitis with other non-specific symptoms, such as
      arthralgias and myalgias. The initial cutaneous manifestations are important in
      early diagnosis of possible ANCA-associated vasculitides with elevated ANCA
      titres.

PMID- 16648919
TI  - Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of
      atopy patch testing and histological examination.
AB  - Atopy patch testing with Japanese cedar pollen extract has been used to
      investigate patients with atopic dermatitis whose condition is exacerbated by
      contact with Japanese cedar pollen. Comparative atopy patch testing, scratch
      tests, and assays for total IgE and specific IgE were performed in 74 patients
      with atopic dermatitis, 5 patients with Japanese cedar pollinosis and 15 control
      subjects. A skin biopsy was performed on any sites that were positive to Japanese
      cedar pollen patch test. The results after 48 h of atopy patch testing were
      compared with the patient's history, skin scratch test and specific IgE. Twenty
      two of the 74 patients (30%) had a history of exacerbation every spring after
      contact with Japanese cedar. Of these patients 68% showed a positive reaction to
      Japanese cedar pollen extract, as did 21% of patients with atopic dermatitis
      without a history of exacerbation by Japanese cedar pollen, 20% of patients with
      Japanese cedar pollinosis without eruption and 7% of control subjects. A
      histological examination revealed eczematous changes and infiltration of
      lymphocytes and eosinophils in atopy patch testing positive sites. In conclusion,
      atopy patch testing with Japanese cedar pollen extract is a useful method for
      investigating trigger factors for eczematous skin lesions in a subgroup of
      patients with atopic dermatitis.

PMID- 16648920
TI  - Postradiation dermatofibrosarcoma protuberans.

PMID- 16648921
TI  - Relapse of cutaneous alternaria infectoria in a renal transplant recipient after
      2 years.

PMID- 16648922
TI  - Dermal melanocytosis associated with GM1-gangliosidosis type 1.

PMID- 16648923
TI  - Successful treatment of dermatomyositis with high-dose intravenous
      immunoglobulin.

PMID- 16648924
TI  - Effective control of rush progression of CD8+ mycosis fungoides with pegylated
      interferon.

PMID- 16648925
TI  - Linear melorheostotic scleroderma without melorheostosis.

PMID- 16648926
TI  - Cutaneous cryptococcosis in an immunocompetent host.

PMID- 16648927
TI  - A case of multiple keratoacanthomas associated with keratoacanthoma centrifugum
      marginatum.

PMID- 16648928
TI  - Myofibroma of the proximal nail fold: an uncommon neoplasm.

PMID- 16648929
TI  - Cutaneous infiltrations can herald an inapparent myelodysplastic syndrome.

PMID- 16648930
TI  - Imatinib-induced erythrodermia in a patient with chronic myeloid leukemia.

PMID- 16648931
TI  - Lymphangiectasias after penectomy, inguinal lymph node dissection, urethrostomy
      and radiation.

PMID- 16648932
TI  - Vestibular papillomatosis: case report and literature review.

PMID- 16648933
TI  - Cutaneous Crohn's disease causing deformity of the penis and scrotum.

PMID- 16648934
TI  - Cytomegalovirus in cutaneous ulcers in a patient with adult T-cell lymphoma.

PMID- 16648935
TI  - Adult T-cell lymphoma/leukaemia developing in a patient with psoriasis treated
      with long-term cyclosporine.

PMID- 16648936
TI  - Persistent painful indurated erythema secondary to bosentan.

PMID- 16648937
TI  - Apocrine hidrocystoma on the finger.

PMID- 16648938
TI  - Amelanotic melanoma--"to be or not to be".

PMID- 16648939
TI  - Cooperative study by the Italian neuroendoscopy group on the treatment of 61
      colloid cysts.
AB  - OBJECTS: Microsurgical resection, stereotactic aspiration and VP shunt have for
      years been the choice options for the treatment of colloid cysts of the third
      ventricle. Recently, endoscopic approaches have aroused increasing interest and
      gained acceptance. Although safer, this minimally invasive approach is considered
      less efficacious than microsurgery. Relatively long-term results are now
      available and some conclusions might be inferred on the usefulness of this
      procedure. MATERIALS AND METHODS: Between 1994 and 2005, 61 patients harbouring a
      colloid cyst of the third ventricle were treated with neuroendoscopic technique
      in 11 Italian neurosurgical centres. Cyst diameters ranged from 6 to 32 mm. A
      flexible endoscope was used in 34 cases, a rigid one in 21, both instruments in
      six. The technique consisted in cyst fenestrations, colloid aspiration,
      coagulation of the internal cyst wall and, occasionally, capsule excision. Mean
      postoperative hospital stay was 6.7 days. Early postoperative neuroimaging
      revealed a cyst residue in 36 cases (mean diameter 4.3 mm). There were two
      complications (3.2%). Follow-up varied between 1 and 132 months (mean 32 months,
      more than 5 years in 17 patients). There were seven asymptomatic recurrences,
      three of them evolving from a previous residue. CONCLUSION: The endoscopic
      approach to the treatment of colloid cysts is safe, effective and well accepted
      by patients. Although asymptomatic, recurrences (11.4%) cast a persisting shadow
      on the long-term results, and, therefore, the controversy with the traditional
      microsurgical treatment remains open.

PMID- 16648940
TI  - Organic anion transporting polypeptides of the OATP/SLCO superfamily:
      identification of new members in nonmammalian species, comparative modeling and a
      potential transport mode.
AB  - Organic anion-transporting polypeptides (human, OATPs; other animals, Oatps; gene
      symbol, SLCO/Slco) form a transport protein superfamily that mediates the
      translocation of amphipathic substrates across the plasma membrane of animal
      cells. So far, OATPs/Oatps have been identified in human, rat and mouse tissues.
      In this study, we used bioinformatic tools to detect new members of the OATP/SLCO
      superfamily in nonmammalian species and to build models for the three-dimensional
      structure of OATPs/Oatps. New OATP/SLCO superfamily members, some of which form
      distinct novel families, were identified in chicken, zebrafish, frog, fruit fly
      and worm species. The lack of OATP/SLCO superfamily members in plants, yeast and
      bacteria suggests the emergence of an ancient Oatp protein in an early ancestor
      of the animal kingdom. Structural models were generated for the representative
      members OATP1B3 and OATP2B1 based on the known structures of the major
      facilitator superfamily of transport proteins. A model was also built for the
      large extracellular region between transmembrane helices 9 and 10, following the
      identification of a novel homology with the Kazal-type serine protease
      inhibitors. Along with the electrostatic potential and the conservation of key
      amino acid residues, we propose a common transport mechanism for all OATPs/Oatps,
      whereby substrates are translocated through a central, positively charged pore in
      a rocker-switch type of mechanism. Several amino acid residues were identified
      that may play crucial roles in the proposed transport mechanism.

PMID- 16648941
TI  - Epithelial fluid transport: protruding macromolecules and space charges can bring
      about electro-osmotic coupling at the tight junctions.
AB  - The purpose of the present work is to investigate whether the idea of epithelial
      fluid transport based on electro-osmotic coupling at the level of the leaky tight
      junction (TJ) can be further supported by a plausible theoretical model. We
      develop a model for fluid transport across epithelial layers based on electro
      osmotic coupling at leaky tight junctions (TJ) possessing protruding
      macromolecules and fixed electrical charges. The model embodies systems of
      electro-hydrodynamic equations for the intercellular pathway, namely the Brinkman
      and the Poisson-Boltzmann differential equations applied to the TJ. We obtain
      analytical solutions for a system of these two equations, and are able to derive
      expressions for the fluid velocity profile and the electrostatic potential. We
      illustrate the model by employing geometrical parameters and experimental data
      from the corneal endothelium, for which we have previously reported evidence for
      a central role for electro-osmosis in translayer fluid transport. Our results
      suggest that electro-osmotic coupling at the TJ can account for fluid transport
      by the corneal endothelium. We conclude that electro-osmotic coupling at the
      tight junctions could represent one of the basic mechanisms driving fluid
      transport across some leaky epithelia, a process that remains unexplained.

PMID- 16648942
TI  - Analyses of 5' regulatory region polymorphisms in human SLC22A6 (OAT1) and
      SLC22A8 (OAT3).
AB  - Kidney excretion of numerous organic anionic drugs and endogenous metabolites is
      carried out by a family of multispecific organic anion transporters (OATs). Two
      closely related transporters, SLC22A6, initially identified by us as NKT and also
      known as OAT1, and SLC22A8, also known as OAT3 and ROCT, are thought to mediate
      the initial steps in the transport of organic anionic drugs between the blood and
      proximal tubule cells of the kidney. Coding region polymorphisms in these genes
      are infrequent and pairing of these genes in the genome suggests they may be
      coordinately regulated. Hence, 5' regulatory regions of these genes may be
      important factors in human variation in organic anionic drug handling. We have
      analyzed novel single nucleotide polymorphisms in the evolutionarily conserved 5'
      regulatory regions of the SLC22A6 and SLC22A8 genes (phylogenetic footprints) in
      an ethnically diverse sample of 96 individuals (192 haploid genomes). Only one
      polymorphism was found in the SLC22A6 5' regulatory region. In contrast, seven
      polymorphisms were found in the SLC22A8 5' regulatory region, two of which were
      common to all ethnic groups studied. Computational analysis permitted phase and
      haplotype reconstruction. Proximity of these non-coding polymorphisms to
      transcriptional regulatory elements (including potential sex steroid response
      elements) suggests a potential influence on the level of transcription of the
      SLC22A6 and/or SLC22A8 genes and will help define their role in variation in
      human drug, metabolite and toxin excretion. The clustering of OAT genes in the
      genome raises the possibility that nucleotide polymorphisms in SLC22A6 could also
      effect SLC22A8 expression, and vice versa.

PMID- 16648943
TI  - Prevalence and persistence of certain serologic types of Streptococcus pyogenes
      in metropolitan Tokyo.
AB  - M-typing was conducted for Streptococcus pyogenes strains isolated within 1 week
      of admission from patients admitted to the Tokyo Metropolitan Toshima Hospital
      for scarlet fever in the 23-year period between 1956 and 1978. M12 was detected
      in the largest number of patients, followed by M6, M4, M3, and M1. T-typing was
      also conducted for Streptococcus pyogenes strains isolated from healthy
      schoolchildren in three different parts of the 20-year period between 1977 and
      1998. T12 was detected in the largest number of children, followed by T28, T1,
      T4, and T6. These results suggested that strains of similar types are prevalent
      in scarlet fever patients and healthy carriers, that these strains become
      prevalent at intervals of several years, and that they are detected every year,
      albeit in a small number of persons, indicating that they are endemic. Isolated
      strains were typed by M-typing and T-typing. The results of typing were identical
      in more than 90% of cases. Comparison of major Streptococcus pyogenes strains
      isolated in Tokyo and three other major cities abroad showed that M12 was
      detected in the largest number of persons in Tokyo and New York and that major
      types were similar in the four cities.

PMID- 16648944
TI  - Prospective multicenter study of the causative organisms of community-acquired
      pneumonia in adults in Japan.
AB  - Although a wide variety of recognized pathogens causes community-acquired
      pneumonia, the precise etiology in Japan remains unknown. We prospectively
      investigated the etiology in 232 patients with community-acquired pneumonia who
      visited 20 community-general hospitals. New diagnostic methods, using polymerase
      chain reaction (PCR) assays and urinary antigen tests were employed, in addition
      to conventional methods. The frequency of identification of causative pathogens
      was high (73.3%), and the leading organism was Streptococcus pneumoniae (24.6%),
      followed by Haemophilus influenzae (18.5%), viruses (16.4%), Chlamydia pneumoniae
      (6.5%), Mycoplasma pneumoniae (5.2%), and Legionella spp. (3.9%). S. pneumoniae
      and M. pneumoniae were the most prevalent pathogens in younger patients, and S.
      pneumoniae and H. influenzae were the most prevalent in elderly patients.
      Multiple or mixed infections were found in 25.9% of all patients and in 35.3%
      with a causal diagnosis. The results have important practical implications for
      the initial treatment of adult patients with community-acquired pneumonia.

PMID- 16648945
TI  - Evaluation of influenza vaccination in health-care workers, using rapid antigen
      detection test.
AB  - A study was conducted to assess the effectiveness of trivalent influenza vaccine
      in preventing influenza and reducing absenteeism in health-care workers of Gifu
      Red Cross Hospital during the 2002-2003 influenza season. Questionnaires were
      distributed to 370 health-care workers, and 366 were returned showing that 237
      had received influenza vaccine and 129 were unvaccinated. The criterion for
      influenza was febrile episodes with a positive reaction on a rapid antigen
      detection test. Among vaccine recipients, the number of influenza infections was
      3.4 per 100 subjects, compared with 8.5 per 100 subjects in nonrecipients (P =
      0.034), and the number of days absent from work per 100 subjects was 9.5,
      compared with 15.1 per 100 subjects in nonrecipients (P = 0.0003). The prevalence
      of adverse reactions to the vaccine was rather low. No serious adverse reactions
      were recorded and no one was absent from work because of adverse reactions. It is
      concluded that influenza vaccine is effective in preventing influenza and
      reducing absenteeism in health-care workers. The results of this study support
      recommendations for influenza vaccination in health-care workers.

PMID- 16648946
TI  - Inactivation of influenza A virus by gentian violet (GV) and GV-dyed cotton
      cloth, and bactericidal activities of these agents.
AB  - Recently we have heard warnings of an outbreak of a highly pathogenic avian
      influenza virus (H5N1). Although, to prevent such infections we must prepare anti
      viral drugs and type-specific vaccines against influenza, we need various simple
      and effective protection methods, such as the use of face masks for public
      health. Also, in any consideration of bacterial infections, methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and
      multidrug-resistant Pseudomonas aeruginosa (MDRP) also pose serious concerns
      which must be addressed. I examined the antiviral activity of gentian violet (GV)
      and GV-dyed cloth against the influenza A (H1N1) virus. Time-kill studies were
      carried out, and the virus titer was determined based on the 50% tissue culture
      infective dose (TCID50). The minimum inhibitory concentrations (MICs) of GV
      against bacteria were also determined, and the killing activities of the GV-dyed
      cloth were judged from viable cell counts. GV immediately killed the influenza A
      virus and this was confirmed by electron microscopy. Moreover, cloth dyed with a
      combination of GV and copper showed not only excellent antiviral activity but
      also prominent bactericidal activities.

PMID- 16648947
TI  - In vitro generation of Salmonella spp. mutants following repeated exposure to
      beta-lactam antibiotics.
AB  - Beta-lactams are a group of drugs considered to be the treatment of choice in
      cases of salmonellosis, although many isolates that are clinically resistant to
      these compounds have been reported. We developed an in vitro model to determine
      the dynamics of the generation of resistant mutants following repeated exposure
      to these drugs. All the isolates exposed repeatedly to amoxicillin and cefotaxime
      exhibit a decrease in their susceptibility to these compounds and to many other
      beta-lactam drugs. However, in many cases this reduction in susceptibility is not
      detected if the CLSI criteria are applied. These mutants with reduced
      susceptibility may be the reason for therapeutic failures, so this phenomenon
      should be studied in greater detail by means of in vitro models or clinical
      studies.

PMID- 16648948
TI  - Study of upper respiratory tract bacterial flora: first report. Variations in
      upper respiratory tract bacterial flora in patients with acute upper respiratory
      tract infection and healthy subjects and variations by subject age.
AB  - With the appearance of penicillin-resistant Streptococcus pneumoniae, there has
      been increasing debate concerning antimicrobial treatments for acute upper
      respiratory tract infection (AURTI) and acute otitis media in children. This
      study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI
      group; 710 subjects) and healthy subjects (HS group; 380 subjects). The
      comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330
      subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and
      older (92 subjects), because the subjects were subgrouped as described above
      dependent on the maturity of the protective immunity. In the HS group 7-74
      subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative
      staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were
      classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus
      pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as
      drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for
      DCP bacteria in the AURTI group tended to be high, it did not reach a significant
      difference, whereas the detection rate for NNF bacteria was significantly lower.
      This trend was also observed to some degree in the other age subgroup. In the 0-6
      subgroup, leukocyte infiltration observed with a microscope indicated the closest
      relationship between S. pneumoniae detection rate and detection quantity. These
      results suggest that in the 0-6 subgroup the tendency for patients with AURTI to
      have NNF bacteria as well as DCP bacteria should be taken into consideration.

PMID- 16648949
TI  - Single dose of cefodizime completely eradicated multidrug-resistant strain of
      Neisseria gonorrhoeae in urethritis and uterine cervicitis.
AB  - Cefodizime (CDZM) has strong antimicrobial activity to Neisseria gonorrhoeae in
      vitro. However, multidrug-resistant N. gonorrhoea emerged and has been increasing
      in Japan. To know the effectiveness of CDZM on gonococcal urethritis and uterine
      cervicitis even in the era of multidrug-resistant N. gonorrhoeae, a clinical
      trial of single-dose therapy of CDZM for gonococcal urethritis and uterine
      cervicitis was conducted. N. gonorrhoeae was eradicated from 100% of patients
      with gonococcal urethritis and uterine cervicitis by a single dose of CDZM. In
      conclusion, CDZM is one of most suitable drugs for the treatment of gonococcal
      genital infection in the era of multidrug-resistant N. gonorrhoeae.

PMID- 16648950
TI  - Evaluation of the effect of terpenoid quinones on Trichophyton mentagrophytes by
      solution and vapor contact.
AB  - The antimicrobial activity against two bacterial strains and three fungi of five
      terpenoid quinones, three related quinones, and a quinone-containing essential
      oil was investigated by broth dilution and by agar vapor and box vapor assays.
      All the quinones, except for coenzyme Q10, exhibited their highest activity
      against Trichophyton mentagrophytes. Thymoquinone showed the most potent
      activity, not only by solution contact but also by vapor contact, with menadione
      the next most potent. Alizarin showed high activity only by solution contact. The
      antibacterial activity was related to the orthoquinone structure (1,2-chloranil
      and 1,2-naphthoquinone) and the antifungal activity was related to the
      paraquinone structure (chloranil, ubiquinone 0, thymoquinone, and menadione).

PMID- 16648951
TI  - Detection of Legionella pneumophila serogroup 7 strain from bathwater samples in
      a Japanese hospital.
AB  - Hospital-acquired legionellosis is one of the serious problems in nosocomial
      infection. For risk assessment of nosocomial Legionella infection, we surveyed
      samples from bathrooms for public use in three hospitals and two nursing homes to
      determine whether Legionella pneumophila was present. A total of 70 hot bathwater
      samples and samples wiped from bathtubs were collected at 1-h intervals. Fifteen
      shower-water and 15 inner-head samples were obtained at the start of a bath.
      Water samples were cultured using the Legionella spp. selective medium, and
      discrimination between L. pneumophila and other Legionella spp. was performed by
      PCR analysis. L. pneumophila serogroup 7 was detected in 1 bathwater and 1 wiped
      sample, both of which were collected 1 h after daily use from the same bathtub in
      a hospital. However, L. pneumophila SG7 was not detected in any other samples.
      Furthermore, the concentrations of free residual chlorine in most bath- and
      shower-water samples were lower than 0.1 mg/l. These results suggest that L.
      pneumophila has become a potential pathogen for nosocomial infections in public
      type hospital baths. From the point of view of an infection-control program, it
      might be advisable to hold the concentration of free residual chlorine at 0.2-0.4
      mg/l, which is generally required for public baths in Japan.

PMID- 16648952
TI  - Effect of fluoroquinolones on plasma glucose levels in fasted and glucose-loaded
      mice.
AB  - In fasted mice, plasma glucose levels were reduced by intraperitoneal
      administration of enoxacin, lomefloxacin, or gatifloxacin (50 mg/kg). A lower
      dose of these fluoroquinolones (5 mg/kg) also reduced the plasma glucose (PG)
      levels in glucose-loaded mice. Ciprofloxacin and levofloxacin did not reduce
      these levels in either fasted or glucose-loaded mice. These results suggest that
      each fluoroquinolone has an individual hypoglycemic action, and fluoroquinolone
      administration after meals might reduce PG levels at lower doses.

PMID- 16648953
TI  - Introduction of the factor of partitioning in the lithogenic enrichment factors
      of trace element bioaccumulation in plant tissues.
AB  - Bioindicators are widely used in the study of trace elements inputs into the
      environment and great efforts have been conducted to separate atmospheric from
      soil borne inputs on biomass accumulation. Many monitoring studies of trace
      element pollution take into account the dust particles located in the plant
      surface plus the contents of the plant tissues. However, it is usually only the
      trace element content in the plant tissues that is relevant on plant health.
      Enrichment factor equations take into account the trace element enrichment of
      biomasses with respect soil or bedrocks by comparing the ratios of the trace
      element in question to a lithogenic element, usually Al. However, the enrichment
      equations currently in use are inadequate because they do not take into account
      the fact that Al (or whichever reference element) and the element in question may
      have different solubility-absorption-retention levels depending on the rock and
      soil types involved. This constrain will become critical when results from
      different sites are compared and so in this article we propose that the
      solubility factors of each element are taken into account in order to overcome
      this constrain. We analysed Sb, Co, Ni, Cr, Pb, Cd, Mn, V, Zn, Cu, As, Hg, and Al
      concentration in different zones of Catalonia (NE Spain) using the evergreen oak
      Quercus ilex and the moss Hypnum cupressiforme as target species. We compared the
      results obtained in rural and non industrial areas with those from the Barcelona
      Metropolitan Area. We observed differences in Al concentrations of soils and
      bedrocks at each different site, together with the differences in solubility
      between Al and the element in question, and a weak correlation between total soil
      content and water extract content through different sites for most trace
      elements. All these findings show the unsuitability of the current enrichment
      factors for calculating lithospheric and atmospheric contributions to trace
      element concentrations in biomass tissues. The trace element enrichment factors
      were calculated by subtracting the part predicted by substrate composition
      (deduced from water extracts from soils and bedrock) from total concentrations.
      Results showed that for most of the trace elements analysed, trace elements
      enrichment factors were higher inside the Barcelona Metropolitan Area than
      outside, a finding that indicates that greater atmospheric inputs occur in urban
      areas. The results show that the most useful and correct way of establishing a
      reference for lithospheric and atmospheric inputs into the plant tissues is,
      first, to analyse samples of the same plant species collected from a number of
      sites possessing similar environmental conditions (climate, vegetation type, soil
      type) and, second, to use this new enrichment factor obtained by subtracting from
      the total concentration in plant tissue the predicted contribution of soil or
      bedrock extracts instead of that of total soil or bedrock concentrations.

PMID- 16648954
TI  - Sediment and suspended matter lead contamination in the gulf of Kavala, Greece.
AB  - Sediment and suspended particulate matter samples from 24 stations in the Gulf of
      Kavala have been examined for lead contamination. Grain size analysis and organic
      matter content were also performed. Total -- anthropogenic sediment lead
      concentrations and enrichment factors at stations close to harbors and chemical
      industries were found higher (up to 209-135 micro g/g and 4.12 respectively), in
      relation to concentrations from the rest of the coastal zone. In the above areas,
      increased suspended particulate lead in the bottom of the water column was also
      recorded (up to 109 micro g/g). Total sediment lead concentrations composed of
      high natural Pb background increased with decreasing grain size, suggesting their
      association with the fine fractions of the sediments (31.1-66.0% mud presence)
      and the organic matter content (6-9% higher values). Overall, higher total lead
      concentrations in the sediments, determined by this work, appear to be
      significantly different from those reported for the Gulf of Kavala in previous
      studies and similar to those detected in other highly contaminated eastern
      Mediterranean coastal areas.

PMID- 16648955
TI  - Biomonitoring in the Boulder River Watershed, Montana, USA: metal concentrations
      in biofilm and macroinvertebrates, and relations with macroinvertebrate
      assemblage.
AB  - Portions of the Boulder River watershed contain elevated concentrations of
      arsenic, cadmium, copper, lead, and zinc in water, sediment, and biota. We
      measured concentrations of As, Cd, Cu, Pb, and Zn in biofilm and
      macroinvertebrates, and assessed macroinvertebrate assemblage and aquatic habitat
      with the objective of monitoring planned remediation efforts. Concentrations of
      metals were generally higher in downstream sites compared with upstream or
      reference sites, and two sites contained metal concentrations in
      macroinvertebrates greater than values reported to reduce health and survival of
      resident trout. Macroinvertebrate assemblage was correlated with metal
      concentrations in biofilm and macroinvertebrates. However, macroinvertebrate
      metrics were significantly correlated with a greater number of biofilm metals (8)
      than metals in invertebrates (4). Lead concentrations in biofilm appeared to have
      the most significant impact on macroinvertebrate assemblage. Metal concentrations
      in macroinvertebrates were directly proportional to concentrations in biofilm,
      indicating biofilm as a potential surrogate for monitoring metal impacts in
      aquatic systems.

PMID- 16648956
TI  - Assessing the impact of leather industry to water quality in the Aojing watershed
      in Zhejiang Province, China.
AB  - The development of the leather industry in the Aojiang watershed of Zhejiang
      province increased the release of waste water. In the waste water, ammonium
      nitrogen (NH(+) (4)-N) and germanium (Ge) are the main pollutants. In recent
      years, literature has documented that the intake of high concentrations of NH(+)
      (4)-N and Ge harms human health and biological species. This paper focuses on
      assessing the trends of NH(+) (4)-N and Ge concentrations in the released waste
      water in Aojiang watershed and on understanding their relationships with the
      released waste water using regression and correlation statistics. The paper also
      utilizes the integrated pollution index to evaluate the water quality in the
      watershed. Preliminary results show that, from 1992 to 1998, the concentrations
      of NH(+) (4)-N and total Ge increased 13 and 14 times, respectively, and they
      decreased somewhat after 1998. The concentrations of NH(+) (4)-N and total Ge are
      positively correlated to the amount of released waste water. These concentrations
      of NH(+) (4)-N and Ge, respectively, exceed 12 and 3 times, of the water
      standards. The water quality in the watershed degraded from Type III in 1992 to
      over Type V in 2003 when they were compared with the national water quality
      standards. It appeared that the pollution had positive correlation with leather
      industry production. The degraded water has no doubt affected human health and
      the ecosystem health. These results can provide scientific information for the
      local government to reasonably adjust the industry structure and reduce the
      pollution to protect the environment.

PMID- 16648957
TI  - Fractionation of aluminum in soil and relation to its concentration in fruits.
AB  - Aluminum concentrations in the fruit samples taken from different regions were
      determined by atomic absorption spectrometry after dry ashing digestion. To
      identify the aluminum phases being most responsible for fruit-available aluminum,
      the soil samples near the fruit plants were also analyzed for aluminum by using
      various digestion and selective extraction reagents. The relation between the
      aluminum concentrations in fruits and in soil extracts was studied. The obtained
      aluminum concentrations in the fruits were in the range of 1.5 to 42.0 mg kg(-1)
      on dry weight basis. It was observed that the aluminum concentrations of morello
      cherry(R(2) = 0.79) and mulberry (R(2) = 0.99) were correlated to the aluminum
      concentrations in citric acid extracts of the soils. While the aluminum
      concentrations of the EDTA and acetic acid extracts in some soils samples include
      35% and 25% of total aluminum, respectively, the other soils contain only 1-2%.

PMID- 16648958
TI  - Characterization of benthic communities and physical habitat in the Stanislaus,
      Tuolumne, and Merced Rivers, California.
AB  - The primary goal of this study was to characterize physical habitat and benthic
      communities (macroinvertebrates) in the Stanislaus, Tuolumne and Merced Rivers in
      California's San Joaquin Valley in 2003. These rivers have been listed as
      impaired water bodies (303 (d) list) by the State of California due to the
      presence of organophosphate (OP) insecticides chlorpyrifos and diazinon, Group A
      pesticides (i.e., organochlorine pesticides), mercury, or unknown toxicity. Based
      on 10 instream and riparian physical habitat metrics, total physical habitat
      scores in the Stanislaus River ranged from 124 to 188 (maximum possible total
      score is 200). The highest total habitat score was reported at the upstream site.
      Tuolumne River physical habitat scores ranged from 86 to 167. Various Tuolumne
      River physical habitat metrics, including total habitat score, increased from
      downstream to upstream in this river. Merced River physical habitat scores ranged
      from 121 to 170 with a significant increase in various physical habitat metrics,
      including total habitat score, reported from downstream to upstream. Channel flow
      (an instream metric) and bank stability (a riparian metric) were the most
      important physical habitat metrics influencing the various benthic metrics for
      all three rivers. Abundance measures of benthic macroinvertebrates (5,100 to
      5,400 individuals) were similar among the three rivers in the San Joaquin
      watershed. Benthic communities in all three rivers were generally dominated by:
      (1) Baetidae species (mayflies) which are a component of EPT taxa generally
      considered sensitive to environmental degradation; (2) Chironomidae (midges)
      which can be either tolerant or sensitive to environmental stressors depending on
      the species; (3) Ephemerellidae (mayflies) which are considered sensitive to
      pollution stress; and (4) Naididae (aquatic worms) which are generally considered
      tolerant to environmental stressors. The presence of 117 taxa in the Stanislaus
      River, 114 taxa in the Tuolumne River and 96 taxa in the Merced River implies
      that the benthic communities in these streams are fairly diverse but without a
      clear definition of benthic community expectations it is unknown if these water
      bodies are actually impaired.

PMID- 16648959
TI  - Neural network based automated interpretation algorithm for combined geophysical
      soundings in coastal zones.
AB  - The fresh water availability in coastal aquifers is an important problem faced by
      a major part of world's population dwelling there. For in situ and dynamic
      characterization of seawater encroachment into coastal aquifers, electrical
      geophysical methods are better suited. However, the resolving power of such data
      in distinguishing saline sands from moist clays in the subsurface is very poor.
      To meet this aspect and also the problem of analyzing voluminous data sets, we
      propose a feed forward back-propagation neural network (BPNN) based approach for
      the analysis of combined vertical electrical and induced polarization soundings.
      Our method is tested on synthetic data computed from available geo-electric
      sections and prevailing subsurface geological information of coastal aquifers of
      East Coast of India. The synthetic data are comprised of 18 combined soundings
      spread over five profiles. 15 out of 18 are used for training the BPNN, while 3
      are used for testing. The trained BPNN (one node each in each of the input and
      output layers and 18 hidden nodes) showed 84.85% accuracy in testing phase for
      distinguishing clays from saline sands. Our method is also tested on real data
      concerning a shaly aquifer in Bahia, Brazil yielding an overall accuracy of
      84.9%, comparable to that of synthetic case; thereby validating our approach.

PMID- 16648960
TI  - Status of the Riparian ecosystem in the upper San Pedro River, Arizona:
      application of an assessment model.
AB  - A portion of Arizona's San Pedro River is managed as a National Riparian
      Conservation Area but is potentially affected by ground-water withdrawals beyond
      the conservation area borders. We applied an assessment model to the Conservation
      Area as a basis for monitoring long-term changes in riparian ecosystem condition
      resulting from changes in river water availability, and collected multi-year data
      on a subset of the most sensitive bioindicators. The assessment model is based on
      nine vegetation bioindicators that are sensitive to changes in surface water or
      ground water. Site index scores allow for placement into one of three condition
      classes, each reflecting particular ranges for site hydrology and vegetation
      structure. We collected the bioindicator data at 26 sites distributed among 14
      reaches that had similar stream flow hydrology (spatial flow intermittency) and
      geomorphology (channel sinuosity, flood-plain width). Overall, 39% of the
      riparian corridor fell within condition class 3 (the wettest condition), 55% in
      condition class 2, and 6% in the driest condition class. Condition class 3
      reaches have high cover of herbaceous wetland plants (e.g., Juncus and
      Schoenoplectus spp.) along the perennial stream channel and dense, multi-aged
      Populus-Salix woodlands in the flood plain, sustained by shallow ground water in
      the stream alluvium. In condition class 2, intermittent stream flows result in
      low cover of streamside wetland herbs, but Populus-Salix remain abundant in the
      flood plain. Perennial wetland plants are absent from condition class 1,
      reflecting highly intermittent stream flows; the flood plain is vegetated by
      Tamarixa small tree that tolerates the deep and fluctuating ground water levels
      that typify this reach type. Abundance of herbaceous wetland plants and growth
      rate of Salix gooddingii varied between years with different stream flow rates,
      indicating utility of these measures for tracking short-term responses to
      hydrologic change. Repeat measurement of all bioindicators will indicate long
      term trends in hydro-vegetational condition.

PMID- 16648961
TI  - Spatial scale of autocorrelation of assemblages of benthic invertebrates in two
      upland rivers in South-Eastern Australia and its implications for biomonitoring
      and impact assessment in streams.
AB  - Spatial autocorrelation in ecological systems is a critical issue for monitoring
      (and a general understanding of ecological dynamics) yet there are very few data
      available, especially for riverine systems. Here, we report here on assemblage
      level autocorrelation in the benthic-invertebrate assemblages of riffles in two
      adjacent, relatively pristine rivers in south-eastern Victoria, Australia (40-km
      reaches of the Wellington [surveys in summers of 1996 and 1997] and Wonnangatta
      Rivers [survey in summer of 1996 only], with 16 sites in each river). We found
      that analyses were similar if the data were resolved to family or to species
      level. Spatial autocorrelation was assessed by using Mantel-tests for the data
      partitioned into different sets of spatial separations of survey sites (e.g. 0-6
      km, 6-12 km, etc.). We found strong small-scale (< or =6 km) autocorrelation in
      the Wellington River, which is consistent with known dispersal abilities of many
      aquatic invertebrates. Surprisingly, there were strong negative correlations at
      longer distance classes for the Wellington River in one of the two summers (20-40
      km) and the Wonnangatta River (12-20 km). That two largely unimpacted, adjacent
      rivers should have such different autocorrelation patterns suggests that impact
      assessment cannot assume dependence or independence of sites a priori. We discuss
      the implications of these results for use of "reference" sites to assess impacts
      at nominally affected sites.

PMID- 16648962
TI  - Assembly of HCV E1 and E2 glycoproteins into coronavirus VLPs.
AB  - Hepatitis C virus (HCV) is believed to assemble by budding into membranes of the
      early secretory pathway, consistent with the membrane location where the viral
      envelope glycoproteins E1 and E2 accumulate when expressed. Coronavirus assembly
      also takes place at pre-Golgi membranes. Here, we generated coronavirus-like
      particles carrying in their envelope chimeric HCV glycoproteins composed of the
      ectodomains of E1 and E2, each fused to the transmembrane plus endodomain of the
      mouse hepatitis coronavirus spike glycoprotein. The chimeric particle system will
      enable structural and functional studies of the HCV glycoproteins.

PMID- 16648963
TI  - On the classification and nomenclature of baculoviruses: a proposal for revision.
AB  - Recent evidence from genome sequence analyses demands a substantial revision of
      the taxonomy and classification of the family Baculoviridae. Comparisons of 29
      baculovirus genomes indicated that baculovirus phylogeny followed the
      classification of the hosts more closely than morphological traits that have
      previously been used for classification of this virus family. On this basis,
      dipteran- and hymenopteran-specific nucleopolyhedroviruses (NPV) should be
      separated from lepidopteran-specific NPVs and accommodated into different genera.
      We propose a new classification and nomenclature for the genera within the
      baculovirus family. According to this proposal the updated classification should
      include four genera: Alphabaculovirus (lepidopteran-specific NPV),
      Betabaculovirus (lepidopteran-specific Granuloviruses), Gammabaculovirus
      (hymenopteran-specific NPV) and Deltabaculovirus (dipteran-specific NPV).

PMID- 16648964
TI  - The continuity of psychopathology from early childhood to preadolescence: a
      prospective cohort study of 3-12-year-old children.
AB  - OBJECTIVE: To study the continuity of psychopathology from the age of 3-12 years.
      METHODS: In a population-based birth cohort, children's emotional and behavioral
      problems were assessed at age 3 using the Child Behavior Checklist 2-3 (CBCL 2
      3), and at age 12 by parents using the CBCL 11-18, and the Youth Self Report
      (YSR) completed by the children. Behavioral ratings were obtained from 800
      subjects at both time points. RESULTS: externalizing problems at age 3 predicted
      both externalizing and internalizing problems among both genders in
      preadolescence. In girls, internalizing behavior at age 3 predicted parent
      reported internalizing behavior, and associated negatively with externalizing
      behavior in self-reports at age 12. Aggressive behavior was found to be
      remarkably stable, and both aggressive and destructive behavior independently
      predicted a wide range of later externalizing and internalizing problems. Parent
      ratings of withdrawal showed stability from early childhood to preadolescence in
      both genders. Somatic complaints of 3-year-old girls independently predicted both
      externalizing and internalizing problems. CONCLUSIONS: The results show the
      complexity of pathways in psychopathology from early childhood to preadolescence.
      In particular, aggressive and destructive behaviors in very early childhood
      predict later problems and necessitate early recognition and possible
      intervention at an early age. An instrument like the CBCL 2-3 is valuable in the
      early detection of children at risk of long-term problems.

PMID- 16648965
TI  - Prevalence of movement disorders in adolescent patients with schizophrenia and in
      relationship to predominantly atypical antipsychotic treatment.
AB  - OBJECTIVE: To examine prevalence of movement disorders (MDs) such as tardive
      dyskinesia (TD), parkinsonism or akathisia in an adolescent population with
      schizophrenia and in relationship to predominantly atypical antipsychotic
      treatment. METHOD: Ninety-three patients (aged 19.6+/-2.2 years) were ascertained
      in this cross-sectional/retrospective study. 76 patients (81.7%) received
      atypical, 10 (10.8%) typical antipsychotics and 7 (7.5%) combinations of
      atypical/typical antipsychotics. MD symptoms were assessed using Tardive
      Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS),
      Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS). RESULTS:
      Movement disorder symptoms were found in 37 patients (39.8%) fulfilling
      strict/subthreshold criteria for TD (5.4/11.8%), parkinsonism (2.2/25.8%) or
      akathisia (1.1/11.8%), respectively. Patients treated with typical antipsychotics
      displayed a significantly higher EPS-score (P=0.036) and a tendency towards a
      higher BAS-score (P=0.061) compared to patients with atypical antipsychotics.
      Treatment durations with typical/atypical antipsychotics showed trends towards
      advantages of atypical antipsychotics with regard to parkinsonism/akathisia
      symptoms (P=0.061; P=0.054), but not with regard to TD symptoms (P=0.003),
      possibly due to confounding effects. CONCLUSION: Under treatment with atypical
      antipsychotics MD symptoms are less prevalent and less pronounced than under
      typical antipsychotics. We speculate that the finding of relatively high
      prevalence rates of subthreshold MD symptoms may be, at least partially,
      explained by previous or combined therapy with typical antipsychotics.

PMID- 16648966
TI  - Comorbid psychopathology in adolescents and young adults treated for substance
      use disorders: a review.
AB  - OBJECTIVE: In a recent review, the prevalence of comorbid psychiatric disorders
      in non-treated adolescents and young adults with substance use disorders (SUD) in
      the general population was summarized. This review looks into the prevalence of
      psychiatric comorbidity in adolescents and young adults treated for SUD. METHOD:
      A computerized literature search was conducted resulting in ten eligible studies.
      RESULTS: The prevalence of comorbid psychiatric disorders varied from 61% to 88%.
      Externalizing disorders, especially Conduct Disorder (CD), were most consistently
      linked to SUD in treatment seeking adolescents. Girls are distinguished by their
      high rate of comorbid internalizing disorders. CONCLUSIONS: Comparison with data
      from community and juvenile justice studies shows an ascending trend of
      comorbidity rates of externalizing disorders from community to clinical and
      finally to juvenile justice samples. It seems that young addicts with comorbid
      disorders are at high risk of ending up in the juvenile justice system.

PMID- 16648968
TI  - P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in
      inflammation, thrombosis, and cancer growth and metastasis.
AB  - Stimulated endothelial cells and activated platelets express P-selectin (CD62P),
      a member of the selectin family of cell adhesion molecules, which interacts with
      P-selectin glycoprotein ligand-1 (PSGL-1, CD162) for leukocyte rolling on
      stimulated endothelial cells and heterotypic aggregation of activated platelets
      onto leukocytes. Cross-linking of PSGL-1 by P-selectin also primes leukocytes
      intracellularly for cytokine and chemoattractant-induced beta2-integrin
      activation for firm adhesion of leukocytes. Furthermore, P-selectin mediates
      heterotypic aggregation of activated platelets to cancer cells and adhesion of
      cancer cells to stimulated endothelial cells. Here we provide a comprehensive
      summary of the functional roles and the biological importance of P-selectin
      mediated cell adhesive interactions in the pathogeneses of inflammation,
      thrombosis, and the growth and metastasis of cancers.

PMID- 16648969
TI  - Monoclonal and bispecific antibodies as novel therapeutics.
AB  - Gene amplification, over-expression, and mutation of growth factors, or the
      receptors themselves, causes increased signaling through receptor kinases, which
      has been implicated in many human cancers and is associated with poor prognosis.
      Tumor growth has been shown to be decreased by interrupting this process of
      extensive growth factor-mediated signaling by directly targeting either the
      surface receptor or the ligand and thereby preventing cell survival and promoting
      apoptosis. Monoclonal antibodies have long been eyed as a potential new class of
      therapeutics targeting cancer and other diseases. Antibody-based therapy
      initially entered clinical practice when trastuzumab/Herceptin became the first
      clinically approved drug against an oncogene product as a well-established
      blocking reagent for tumors with hyperactivity of epidermal growth factor
      signaling pathways. In the first part of this review we explain basic terms
      related to the development of antibody-based drugs, give a brief historic
      perspective of the field, and also touch on topics such as the "humanization of
      antibodie" or creation of hybrid antibodies. The second part of the review gives
      an overview of the clinical usage of bispecific antibodies and antibodies "armed"
      with cytotoxic agents or enzymes. Further within this section, cancer-specific,
      site-specific, or signaling pathway-specific therapies are discussed in detail.
      Among other antibody-based therapeutic products, we discuss: Avastin
      (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX
      210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000),
      Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath
      (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of
      the review deliberates upon potential problems associated with cancer
      immunotherapy.

PMID- 16648970
TI  - The distinctive role of small heat shock proteins in oncogenesis.
AB  - Recently, the role of small heat shock proteins (HSPs) has been widely recognized
      in cancer research. Small HSPs are tumorprotective via numerous, independent
      mechanisms such as: oxidative stress, protection preventing protein denaturation,
      anti-apoptotic activity, and likely direct suppression of the immune system.
      However, it is unclear whether they play any role in the initial steps in
      carcinogenesis. This article seeks to familiarize the reader with general
      characteristics of small HSPs (especially HSP-27, alphaA/B-crystallins), their
      tissue distribution with special regard on expression in malignant specimens, and
      biological properties of intracellular HSP-27 and alphaA/B-crystallins promoting
      tumor genesis and growth. A separate chapter describes immunomodulatory
      characteristics of extracellular HSP-27 with special emphasis on their plausible
      effect on the neoplasm development.

PMID- 16648971
TI  - Novel therapies of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter
      spp. infections: the state of the art.
AB  - Gram-negative non-fermenting bacilli, particularly Pseudomonas aeruginosa and
      Acinetobacter spp., are important opportunistic pathogens in hosppitalized
      patients, contributing to their morbidity and mortality. Recently, a rapid
      increase in frequency of multidrug-resistant clinical strains is being recorded,
      making the available therapeutic options very limited. Apart from the development
      of novel classes of antimicrobials, there is renewed interest in the use of old
      agents or new combinations of available drugs. Numerous in vitro investigations
      have been reported on the efficacy of different antimicrobials; however, they
      should be evaluated in experimental infection models and clinical trials. Novel
      approaches are being investigated, such as inhibition of virulence factor
      expression by pathogens or inhibition of their metabolic pathways. The use of
      bacteriophages, particularly those genetically modified, remains an alternative
      option in the therapy of infections caused by multidrug-resistant strains.
      Several vaccines against P. aeruginosa are under development. Apart from therapy
      with antimicrobial agents, eradication of outbreaks comprises implementation of
      strict infection control measures and prudent use of antimicrobials.

PMID- 16648972
TI  - The migration of bone marrow-derived non-hematopoietic tissue-committed stem
      cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner.
AB  - INTRODUCTION: Recently we identified in bone marrow (BM) by employing chemotactic
      isolation to SDF-1 gradient combined with real time RT-PCR analysis a mobile
      population of CXCR4+ BM mononuclear cells that express mRNA for various markers
      of early tissue-committed stem cells (TCSCs). In this study we evaluated whether
      TCSCs respond to other motomorphogens, such as hepatocyte growth factor (HGF) and
      leukemia inhibitory factor (LIF). MATERIALS AND METHODS: We again employed
      chemotactic isolation combined with real-time RT-PCR analysis to assess whether
      murine and human BM contain TCSCs that respond to HGF and LIF gradients. We also
      evaluated expressions of HGF and LIF in damaged organs. RESULTS: We noted that
      the number of TCSCs is highest in BM from young (1- to 2-month-old) mice and
      decreases in 1-year-old animals. Murine and human TCSCs 1) respond to HGF and LIF
      gradients in addition to an SDF-1 gradient, 2) reside in populations of BM
      derived non-hematopoietic CD45-cells, and 3) are released (mobilized) from BM
      into the peripheral blood (PB) during tissue injury (e.g. after partial body
      irradiation). CONCLUSIONS: These findings further support our theory of the BM as
      a "hideout" for TCSCs and we suggest that their presence in BM tissue should be
      considered before experimental evidence is interpreted simply as
      transdifferentiation/plasticity of hematopoietic stem cells. Since we
      demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged
      tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the
      BM into the PB, from which they are subsequently chemoattracted to damaged
      organs, where they play a role in tissue repair/regeneration.

PMID- 16648973
TI  - Toll-like receptors types 2 and 6 and the apoptotic process in human neutrophils.
AB  - INTRODUCTION: Neutrophils (PMN) apoptosis plays an important role in limiting the
      last phase of inflammatory processes. It is unknown whether Toll-like receptor
      (TLR)2 acts independently or together with TLR6 in this process. MATERIALS AND
      METHODS: The aim of this study was to estimate the relationship between the
      expressions of TLR2 and TLR6 and the apoptosis of human neutrophils in
      physiological conditions. We investigated the influence of recombinant human
      interleukin (IL)-18 and N-formyl-metionyl-leucyl-phenylalanine (fMLP) on the
      relationships between these receptors and neutrophil apoptosis. RESULTS: Our
      results showed that after 4-h incubation, the percentage of apoptotic PMNs
      significantly increased compared with PMN counts before incubation. The stronger
      expression of TLR2 on the neutrophils suggests that this receptor contributes
      more significantly to the induction of PMN apoptosis than does TLR6. We also
      demonstrated an influence of recombinant human IL-18 (rhIL-18) on the expression
      of TLR6, whereas this effect was not observed in the expression of TLR2. We
      observed that both rhIL-18 and fMLP inhibited the apoptosis of PMNs and that rhIL
      18 had a stronger effect than fMLP. CONCLUSIONS: The obtained results suggest
      that not only TLR2, but also TLR6 plays an important role in the regulation of
      the apoptosis of PMNs. Changes in the expression of TLR6 and inhibition of
      apoptosis of PMNs by rhIL-18 seem to confirm the vital role this receptor and of
      rhIL-18 in regulating the survival of these cells. These data can be useful in
      developing methods to regulate PMN apoptosis in conditions associated with their
      excessive and unfavorable activation.

PMID- 16648974
TI  - Elevated TGF-beta1 concentration in bronchoalveolar lavage fluid from patients
      with primary lung cancer.
AB  - INTRODUCTION: Transforming growth factor (TGF)-beta is one of numerous inhibitory
      factors produced by cancer cells that regulate antitumor immunity. The aim of
      this study was to evaluate TGF-beta1 levels and lymphocyte subsets in the
      broncholaveolar lavage fluid (BALF) of patients with primary lung cancer and to
      analyze the interdependence of these parameters. MATERIALS AND METHODS: BALF
      samples were collected from 38 patients with primary lung cancer prior to
      treatment and from 23 healthy volunteers. Concentrations of TGF-beta1 were
      measured in two independent lots of samples using a commercially available
      sandwich ELISA kit after concentration of the supernatants. Differential cell
      counts in the BALF were performed on slides stained with the May Grunwald Giemsa
      method. Flow cytometry with monoclonal antibodies was applied for lymphocyte
      phenotyping. RESULTS: A higher level of TGF-beta1 in the BALF of patients
      compared with the healthy subjects was observed in both lots of samples (3.23+/
      2.96 pg/ml vs. 1.05+/-0.95 pg/ml, p<0.05, and 16.1+/-19.3 pg/ml vs. 10.1+/-11.1
      pg/m,, respectively, difference not significant). There was significant positive
      correlation of the TGF-beta1 level with the proportion of lymphocytes and
      negative correlation with both the proportion of macrophages and the percentage
      of cytotoxic and activated T lymphocytes. CONCLUSIONS: Our findings confirmed
      that TGF-beta takes part in the local response in the course of primary lung
      cancer.

PMID- 16648975
TI  - [Assessment of the number of cardio- and cerebrovascular events due to rofecoxib
      (Vioxx) in Germany between 2001 and 2004].
AB  - BACKGROUND AND PURPOSE: After the recall of rofecoxib (Vioxx), there was repeated
      national and international discussion on the potential number of patients harmed
      by causally related cardio- and cerebrovascular events. In individual cases, it
      cannot be determined whether a myocardial infarction or stroke that occurred
      during rofecoxib therapy was actually directly caused by this drug. On the basis
      of the results of the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial and
      German prescription data provided by the Scientific Institute of the Local Health
      Care Fund, the authors therefore conservatively estimated the number of patients
      harmed by rofecoxib in Germany between 2001 and 2004. METHODS: Under simplifying
      assumptions that, as in the VIGOR study, the risk of rofecoxib or naproxen
      therapy can be described by a Cox model with exponentially distributed event
      times, it is possible to calculate the daily risk of cardio- and cerebrovascular
      events in patients treated with these drugs. The estimated number of patients
      experiencing cardio- and cerebrovascular events under rofecoxib or naproxen
      therapy can be calculated by multiplying the daily risks by the defined daily
      doses prescribed in Germany. The difference between these numbers produces the
      estimated number of patients harmed by rofecoxib. RESULTS: On the basis of the
      data pool, a total of 7,092 additional diseased or deceased patients due to
      rofecoxib therapy were estimated (95% confidence interval: 2,004-15,416). The
      simplifying assumptions made together with the underreporting of events in the
      VIGOR trial are more likely to lead to an underestimation than an overestimation
      of affected patients. When assessing the benefit-harm ratio of rofecoxib, it
      needs to be considered that its protective gastrointestinal effects were not
      assessed compared with the optimum long-term therapy. It can be assumed that a
      comparison of rofecoxib with a combination of nonsteroidal anti-inflammatory
      drugs (NSAIDs) and gastric mucosal barrier protectors (e. g., misoprostol) would
      not have shown an advantage in favor of rofecoxib therapy. CONCLUSION: The
      example of rofecoxib and the relatively high number of patients harmed by it in
      Germany indicate that, before widely prescribing a new drug, a more thorough
      assessment of the benefit-harm ratio of the drug is required as well as a
      stronger consideration of therapeutic alternatives and a timely conduct of
      meaningful clinical studies. The results of these studies should be promptly
      communicated in full to physicians and patients.

PMID- 16648976
TI  - [Importance of tilt-table testing compared with Schellong's test for the
      diagnosis of orthostatic dysregulations/syncopes].
AB  - PURPOSE: The study compares the importance of tilt-table testing and Schellong's
      test for the diagnosis of syncopes. PATIENTS AND METHODS: In a prospective
      clinical trial 100 consecutive patients (45 males, 55 females) were included. The
      index symptom for inclusion was a former syncope or presyncope in the patients'
      history. The tilt-table testing procedure was performed according to a modified
      version of the Westminster protocol. Following this procedure, Schellong's test
      was performed in 83 of the patients. RESULTS: During tilt-table testing 34
      patients suffered from orthostatic dysautonomy with syncope or neuro-cardiogenic
      syncope. 29 of these symptomatic patients also underwent Schellong's test.
      However, only four patients showed a borderline positive finding, whereas a
      clearly positive result was seen in six patients. These patients had shown
      orthostatic dysautonomies with syncopes during tilt-table testing. No patient
      suffered from a syncope or presyncope during Schellong's test. CONCLUSION:
      Schellong's test is suitable as a diagnostic procedure for orthostatic
      dysregulation only, and tilt-table testing is highly superior for objectification
      of the diagnosis and differentiation of syncope.

PMID- 16648977
TI  - [Mild hypothermia for neuroprotection after cardiac arrest].
AB  - The favorable effect of hypothermia on brain damage resulting from cardiac arrest
      was first demonstrated in animal studies. Subsequent small-scale human studies
      have also shown positive effects. In 2002, two large randomized studies
      investigating the use of controlled mild hypothermia after resuscitation were
      published in the New England Journal of Medicine. The results convincingly showed
      a positive effect on survival and neurologic outcome. Based on the currently
      available data, the International Liaison Committee on Resuscitation (ILCOR)
      strongly recommends that unconscious adult patients who are resuscitated after
      ventricular fibrillation be cooled to temperatures between 32 and 34 degrees C
      for 12-24 h.

PMID- 16648978
TI  - [Schimke immuno-osseous dysplasia. A pediatric disease reaches adulthood].
AB  - BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive
      multisystemic disorder caused by mutations of the SMARCAL 1 gene (SWI/SNF
      related, matrix-associated, actin-dependent regulator of chromatin, subfamily a
      like 1). CLINICAL FEATURES: Main clinical features are: disproportional growth
      deficiency due to spondyloepiphyseal dysplasia, nephrotic syndrome with focal and
      segmental glomerulosclerosis, and defective cellular immunity. Patients with
      severe SIOD have life-limiting complications like cerebral ischemia due to vaso
      occlusive processes. Only a few patients reached adulthood. CASE REPORTS: The
      clinical course of four adult SIOD patients is presented. CONCLUSION: Even
      patients with severe SIOD can reach adulthood. Therefore, doctors working in the
      field of internal medicine and family doctors should be familiar with the
      clinical picture of SIOD.

PMID- 16648979
TI  - [Rheumatology -- Part 3. Research news concerning epidemiology, diagnosis, and
      therapy of primary systemic vasculitides].
AB  - Antineutrophil cytoplasmic autoantibody-(ANCA-)associated vasculitides, immune
      complex-mediated vasculitides and granulomatous arteritides of unknown etiology
      belong to the group of primary systemic vasculitides. Numerous in vitro and in
      vivo studies have underscored the role of ANCA in the pathogenesis of ANCA
      associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis,
      Churg-Strauss syndrome) in the meantime. Whereas the pathogenicity of
      myeloperoxidase (MPO) ANCA has been supported by data from various animal models
      in the past, the in vivo pathogenicity of proteinase 3 (PR3) ANCA has been
      demonstrated in an animal model only recently. Other studies showed an altered T
      cell response in Wegener's granulomatosis. Hepatitis C virus-(HCV-)associated
      cryoglobulinemic vasculitis is mediated by immune complexes. Recent data suggest
      that the HCV core particles concentrated in the cryoprecipitate apparently play a
      role in the interaction of cryoglobulin and endothelial cells and neutrophil
      granulocytes. Data from the European Vasculitis Study Group (EUVAS) demonstrate
      the efficacy of azathioprine in maintaining remission in ANCA-associated
      vasculitides on the basis of large patient numbers. Biologicals play an
      increasing role in the treatment of refractory vasculitis.

PMID- 16648980
TI  - [The impact of social and institutional characteristics on the appropriateness of
      invasive cardiologic procedures].
AB  - BACKGROUND AND PURPOSE: Germany has the highest per capita rate of invasive
      cardiologic procedures in Europe. An aim of the SULEIKA study was to present a
      clearer picture of this important area of health care. METHODS: Clinical data
      along with social characteristics of patients were acquired by means of
      questionnaires. An additional survey was established to collect data about the
      treating institution. Clinical information was used to define the appropriateness
      of coronary angiographies and percutaneous coronary interventions. A possible
      impact of social or institutional characteristics on the appropriateness was
      examined. RESULTS: 549 of 709 diagnostic coronary angiographies (77.4%) were
      rated "appropriate", 54 (7.6%) as "equivocal", and 106 (15%) as "inappropriate".
      245 of 317 coronary interventions (77.3%) were rated "appropriate", 40 (12.6%) as
      "equivocal", and 32 (10.1%) as "inappropriate". Social and institutional impact
      were found for invasive diagnostics but not for PCI. CONCLUSION: Social
      characteristics of patients and institutional characteristics have only a
      marginal impact on the indication of invasive cardiologic procedures. A trend
      toward "overdiagnostics" within the group of younger patients has been noticed,
      even in the case of missing hard medical evidence. A serious deficit of health
      care research can be found. Consented criteria to assess the appropriateness of
      medical treatments are missing. More research has to be done in the field of
      concepts and processes controlling the distribution and movement of patients into
      different sections of the health care system. Validated, standardized and
      comprehensive data for an international comparison of decisions about medical
      treatments are needed.

PMID- 16648981
TI  - [Ascites--only a symptom of liver disease?].

PMID- 16648982
TI  - [Therapy with peginterferon alfa in a patient with polyneuropathy caused by
      hepatitis C-associated vasculitis].
AB  - BACKGROUND: Liver cirrhosis and hepatocellular carcinoma are typical consequences
      of chronic hepatitis C. Also other comorbidities, such as polyneuropathy, can be
      associated with chronic hepatitis C. Therapy of polyneuropathy is controversial,
      because immunosuppressive therapy can accelerate chronic hepatitis C. Also
      antiviral therapy of chronic hepatitis C with interferon-alpha can aggravate
      polyneuropathy. CASE REPORT: The presented case study describes a patient with
      vasculitic neuropathy without cryoglobulinemia associated with chronic hepatitis
      C. The predominant symptom was pain in the lower leg. Despite immunosuppressive
      therapy with cortisone and methotrexate (MTX), symptoms exacerbated following
      therapy with cyclophosphamide. Because of further lacking amelioration of
      symptoms, the patient was treated with peginterferon alfa-2a and ribavirin, which
      led to prompt marked and persistent amelioration of symptoms. Hepatitis C virus
      could be eliminated sustainedly (SVR [sustained virological response]).
      CONCLUSION: In this case report, causal therapy of chronic hepatitis C with
      peginterferon alfa-2a and ribavirin has proven to be effective in a patient with
      hepatitis C-associated polyneuropathy.

PMID- 16648983
TI  - [DRG and coding: case splitting and case organization].

PMID- 16648984
TI  - [The German competence network stroke: researching -- promoting -- networking].
AB  - BACKGROUND: Stroke is the most frequent neurologic disease, one of the most
      frequent reasons for disability and the third most frequent cause of death in
      Germany. Only the coordination of prevention, therapy in the acute setting and
      rehabilitation will improve the socioeconomic burden of stroke. IMPLEMENTATION
      AND RESULTS: The Competence Net Stroke (www.schlaganfallnetz.de) substantially
      contributes to these efforts by linking leading research groups together,
      improving communication, exchanging knowledge between clinicians, researchers and
      patients, as well as advancing public health science and quality assurance. Since
      the initiation of the Competence Net Stroke by the German Ministry of Education
      and Research in 1999, researchers and clinicians have implemented and expanded
      corporate databanks that jointly answer pressing questions in stroke imaging,
      epidemiology, and genetics. The progress that has been made is largely due to the
      formation of joint standard protocols at several independent institutions. The
      multicenter approach enabled the competence net to build up specialized criteria
      in magnetic resonance imaging (MRI). These criteria guide the clinician to those
      patients, who profit from thrombolysis beyond the 3-h time window. In addition,
      the Competence Net Stroke succeeded in reliably detecting cerebral hemorrhage
      with MRI. PROGRESSION AND PERSPECTIVES: Since 2005, and the beginning of the
      third funding period, the Competence Net Stroke consists of nine sub-nets. The
      integrative, rather than dominating, structure eases flexible reactions to new
      developments and findings in research. The Competence Net Stroke can more
      straightforwardly adopt new, promising research areas and end funding of those
      which are unsuccessful. The future and continuity of the Competence Net Stroke
      are secured by the acquisition of alternative funding such as
      "Sonderforschungsbereiche", the sixth European framework program, industrial
      partners, and health insurance.

PMID- 16648985
TI  - [Stiffness in the fingers and inability to close the fist in a 58-year-old
      patient with diabetes mellitus].

PMID- 16648986
TI  - [Innovation or pseudo-innovation: that is the question].

PMID- 16648987
TI  - In vitro and in vivo potentiating the cytotoxic effect of radiation on human U251
      gliomas by the c-Met antisense oligodeoxynucleotides.
AB  - C-Met, a receptor tyrosine kinase, and its ligand, hepatocyte growth factor
      (HGF), are critical in cellular proliferation, motility, and invasion, and are
      known to be overexpressed in gliomas, which are related to the repair of damaged
      DNA. In this study, we investigated both in vitro and in vivo whether inhibition
      of the c-Met gene by antisense oligonucleotides (ODNs) enhances the cytotoxic
      effect of radiation on human U251 gliomas. A volume of 100 nM of c-Met antisense
      ODNs inhibited the level of mRNA by more than 95% and reduced the protein
      expression by about 70%. Treatment of human U251 glioma cells with 100 nM of c
      Met antisense ODNs significantly enhanced the radiation-induced cell kill
      compared to control cells, and cells treated with nonsense ODNs. When the glioma
      cells were implanted in the cisterna magna of nude mice followed by treatment
      with c-Met antisense ODNs, the survival time of the nude mice was markedly
      prolonged compared to that of the untreated group (P < 0.001, logrank test). In
      addition, the combination of antisense ODNs and irradiation extended the survival
      time of the glioma-bearing nude mice much longer than could be achieved with
      radiation alone (P < 0.0001, logrank test). These results suggest that inhibition
      of c-Met can be expected to serve as a novel potentiator for radiation therapy in
      human U251 gliomas.

PMID- 16648988
TI  - Spinal myxopapillary ependymoma outcomes in patients treated with surgery and
      radiotherapy at M.D. Anderson Cancer Center.
AB  - This study was undertaken to determine the disease outcomes in patients treated
      with surgery alone or surgery and adjuvant radiotherapy (RT) for myxopapillary
      ependymoma (MPE) of the spine. The medical records of 35 patients with MPE
      treated at The University of Texas M.D. Anderson Cancer Center between December
      1968 and July 2002 were reviewed. The endpoints analyzed were progression-free
      survival (PFS), overall survival, and local control. The median age of patients
      was 35 years (range, 14-63 years), and the male to female ratio was 2.5:1. In
      total, 21 (60%) patients underwent a gross total resection, 13 (37%) a subtotal
      resection, and 1 (3%) a biopsy only; 22 of them (63%) also received adjuvant RT.
      The median follow-up was 10.7 years. The 10-year overall survival, PFS, and local
      control rates for the entire group were 97%, 62%, and 72%, respectively. Of 11
      patients 5 (45%) who had undergone gross total resection alone had recurrence. A
      total of 12 (34%) patients had disease recurrence, all in the neural axis; 8 of
      them had treatment failure at the primary site only, 3 in the distant neural axis
      only, and 1 at the primary site and in the distant neural axis. Patient age (> 35
      years; P = 0.002) and adjuvant RT (P = 0.04) significantly affected PFS. The long
      term patient survival duration for MPE managed with surgery and adjuvant RT is
      favorable. Regardless of the extent of resection, adjuvant RT appears to
      significantly reduce the rate of tumor progression. Failures occurred exclusively
      in the neural axis, mainly at the primary site.

PMID- 16648989
TI  - Iron loading: a risk factor for osteoporosis.
AB  - Iron loaded persons are at increased risk for infection, neoplasia, arthropathy,
      cardiomyopathy and an array of endocrine and neurodegenerative diseases. This
      report summarizes evidence of increased risk of iron loading for osteoporosis.
      Iron suppresses bone remodeling apparently by decreasing osteoblast formation and
      new bone synthesis. Low molecular mass iron chelators as well as a natural
      protein iron chelator, lactoferrin, may be useful in prevention of osteoporosis.

PMID- 16648992
TI  - Major histocompatibility complex variation in the endangered crested ibis
      Nipponia nippon and implications for reintroduction.
AB  - The major histocompatibility complex (MHC), with its extraordinary levels of
      genetic variation, is thought to be an essential aspect of the ability of an
      organism to recognize different parasites and pathogens. It has also been
      proposed to regulate reproductive processes in many aspects. Here we examine the
      genetic variation of the second exon of the MHC class II B genes of the crested
      ibis, an endangered species known to descend from just two breeding pairs
      rediscovered in 1981. Only five alleles are identified by single-strand
      conformation polymorphism (SSCP) analysis of 36 samples taken from both wild and
      captive populations, and a comparatively low level of divergence between MHC
      alleles is observed. We suggest that representative sampling of individuals with
      most of the different MHC allele genotypes to constitute a founder population,
      together with the monitoring of the pathogen status of candidate sites before
      release, is of great importance for raising the success rate of reintroduction
      for the crested ibis.

PMID- 16648993
TI  - Genetic relationship of Chinese and Japanese gamecocks revealed by mtDNA sequence
      variation.
AB  - Cockfighting has a very long history dating back to as early as 2500 years ago in
      China. Cockfighting was intertwined with human cultural traditions, helped
      disperse chickens across the world, and influenced the subsequent breed
      selection. Therefore, tracing the origin of gamecocks could mirror the
      distribution of the cockfighting culture. In this study, we compared the
      available mtDNA control region sequences in Chinese and Japanese gamecocks to
      test the recently proposed hypothesis behind the dual origin of the Japanese
      cockfighting culture (from China and Southeast Asia independently). We assigned
      gamecock mtDNAs to different matrilineal components (or phylogenetic clades) that
      emerged from the phylogenetic tree and network profile, and compared the
      frequency differences between Chinese and Japanese gamecocks. Among the six
      clades (A-F) identified, Japanese gamecocks were most frequently found in clades
      C and D (74%, 32/43), whereas more than half of the Chinese gamecock samples
      (69%, 35/51) were grouped in clades A and B. Haplotypes in Japanese gamecocks
      assigned to clades A, B, and E were either shared with those of the Chinese
      samples or differed from the close Chinese types by no more than a three-mutation
      distance. This genetic pattern is in accordance with the proposed dual origin of
      Japanese gamecocks but has left room for single origin of Japanese gamecocks from
      China. The genetic structure of gamecocks in China and Japan might also be
      influenced by subsequent breed selection and conservation after the initial
      gamecock introduction.

PMID- 16648994
TI  - Extensive Natural Hybridization Between Two Geckos, Gekko tawaensis and Gekko
      japonicus (Reptilia: Squamata), Throughout Their Broad Sympatric Area.
AB  - The status of natural hybridization between the two Japanese geckos, Gekko
      tawaensis and Gekko japonicus, was surveyed by use of 15 diagnostic allozyme
      loci. Of 438 specimens examined, 9 were identified as F(l), 1 was a first
      backcross with G. japonicus, and 15 were identified as more successive
      generations. Hybridizations were detected at 7 of the 15 localities interspersed
      throughout a broad sympatric area of the two species, forming a mosaic hybrid
      zone. A comparison of species-hybrid composition between 2-year samples from a
      single locality and a 5-year interval showed no evidence for progressive
      introgression or establishment of a hybrid swarm, despite constant emergences of
      F(l) hybrids. Nonprevalence of the hybrid genotypes was also indicated by the
      analysis using hybrid index scores for all other localities examined. These
      results suggest that strong selection acts against hybrid genotypes.
      Morphological features of hybrid individuals were also provided.

PMID- 16648995
TI  - Digestion of I-PpoI recognition sites in unfavorable sequence contexts achieved
      by changing the reaction conditions.

PMID- 16648996
TI  - Molecular identification of tropical tasar silkworm (Antheraea mylitta) ecoraces
      with RAPD and SCAR markers.
AB  - The tropical tasar silkworm, Antheraea mylitta, has several ecoraces, 10 of which
      are commercially exploited for the production of tasar silk. These ecoraces are
      identified by morphological markers that are greatly influenced by photoperiod,
      humidity, altitude, and host plants. The DNA markers, random amplification of
      polymorphic DNA (RAPD), and sequence-characterized amplified region (SCAR) are
      identified to complement the existing morphological markers. Seven RAPD bands are
      selected that identify 8 of the 10 ecoraces. These identified RAPD fragments are
      sequenced and primers are designed for SCAR markers. Of the seven sets of
      primers, a single primer pair produced polymorphic SCAR bands that diagnose 5 of
      the 10 ecoraces. All 10 ecoraces are identified by the use of RAPD and SCAR
      markers together.

PMID- 16648999
TI  - Peer victimization, aggression, and their co-occurrence in middle school:
      pathways to adjustment problems.
AB  - An ethnically diverse sample of 6th-grade students completed peer nomination
      procedures that were used to create subgroups of students with reputations as
      victims, aggressors, aggressive victims, and socially adjusted (neither
      aggressive nor victimized). Self-report data on psychological adjustment,
      attributions for peer harassment, and perceived school climate were gathered. In
      addition, homeroom teachers rated participating students on academic engagement
      and students' grades were collected from school records. Victims reported the
      most negative self-views, aggressors enjoyed the most positive self-views, and
      aggressive victims fell between these two groups, although their psychological
      profile more closely resembled that of victims. However, all three subgroups
      encountered more school adjustment problems when compared to their socially
      adjusted classmates. Different pathways to school adjustment problems for
      aggressors and victims were examined. For victims, characterological self-blame
      for victimization and psychological maladjustment were the key mediators, whereas
      for aggressors, the significant pathway was mainly through perceived unfairness
      of school rules. Analyses by ethnicity revealed that African American boys were
      most likely to be perceived as aggressive and as aggressive victims and they were
      doing most poorly in school. Implications for intervention with subgroups of
      problem behavior youth and the particular vulnerabilities of African American
      adolescents were discussed.

PMID- 16649000
TI  - The Short Mood and Feelings Questionnaire (SMFQ): a unidimensional item response
      theory and categorical data factor analysis of self-report ratings from a
      community sample of 7-through 11-year-old children.
AB  - Item response theory (IRT) and categorical data factor analysis (CDFA) are
      complementary methods for the analysis of the psychometric properties of
      psychiatric measures that purport to measure latent constructs. These methods
      have been applied to relatively few child and adolescent measures. We provide the
      first combined IRT and CDFA analysis of a clinical measure (the Short Mood and
      Feelings Questionnaire--SMFQ) in a community sample of 7-through 11-year-old
      children. Both latent variable models supported the internal construct validity
      of a single underlying continuum of severity of depressive symptoms. SMFQ items
      discriminated well at the more severe end of the depressive latent trait. Item
      performance was not affected by age, although age correlated significantly with
      latent SMFQ scores suggesting that symptom severity increased within the age
      period of 7-11. These results extend existing psychometric studies of the SMFQ
      and confirm its scaling properties as a potential dimensional measure of symptom
      severity of childhood depression in community samples.

PMID- 16649001
TI  - A population-based twin study of parentally reported tactile and auditory
      defensiveness in young children.
AB  - Some adults and children exhibit defensive behaviors to tactile or auditory
      stimulation. These symptoms occur not only in subsets of children with ADHD,
      autism, and Fragile X syndrome, but also in the apparent absence of accompanying
      disorders. Relatively little research explores the correlates and antecedents of
      sensory defensiveness. Using a population-based sample of 1,394 toddler-aged
      twins, mothers reported on tactile and auditory defensiveness, temperament, and
      behavior problems. The incidence of defensive symptoms was widely distributed,
      with some accumulation of cases in the extreme range. Girls were overrepresented
      in the extreme tactile defensiveness group. Both auditory and tactile
      defensiveness were modestly associated with fearful temperament and anxiety, but
      they were relatively distinct from other common dimensions of childhood
      behavioral dysfunction. Twin correlations for the full range of scores and
      concordance rates for the extremes suggested moderate genetic influences, with
      some indication that the tactile domain might be more heritable than the auditory
      domain.

PMID- 16649002
TI  - The development of aggression in 18 to 48 month old children of alcoholic
      parents.
AB  - This study examined the development of aggressive and oppositional behavior among
      alcoholic and nonalcoholic families using latent growth modeling. The sample
      consisted of 226 families assessed at 18, 24, 36, and 48 months of child age.
      Results indicated that children in families with nonalcoholic parents had the
      lowest levels of aggressive behavior at all time points compared to children with
      one or more alcoholic parents. Children in families with two alcoholic parents
      did not exhibit normative decreases in aggressive behavior from 3 to 4 years of
      age compared to nonalcoholic families. However, this association was no longer
      significant once a cumulative family risk score was added to the model. Children
      in families with high cumulative risk scores, reflective of high parental
      depression, antisocial behavior, negative affect during play, difficult child
      temperament, marital conflict, fathers' education, and hours spent in child care,
      had higher levels of aggression at 18 months than children in low risk families.
      These associations were moderated by child gender. Boys had higher levels of
      aggressive behavior at all ages than girls, regardless of group status.
      Cumulative risk was predictive of higher levels of initial aggressive behavior in
      both girls and boys. However, boys with two alcoholic parents had significantly
      less of a decline in aggression from 36 to 48 months compared to boys in the
      nonalcoholic group.

PMID- 16649007
TI  - Safe lifting in patients with chronic low back pain: comparing FCE lifting task
      and Niosh lifting guideline.
AB  - INTRODUCTION: Both the floor-to-waist lifting task of the Isernhagen Work Systems
      Functional Capacity Evaluation (IWS FCE) and recommended weight limit (RWL) of
      the NIOSH produce safe lifting weights and are used world-wide nowadays. It is
      unknown whether they produce similar safe lifting weights. Aim of this study was
      to compare FCE performance on the floor-to-waist lifting task and RWL of the
      NIOSH lifting guideline for this task, in patients with chronic low back pain
      (CLBP). METHODS: Ninety-two patients performed the FCE lifting task. RWL was
      calculated for this task. Performance was compared with RWL. A lifting index was
      calculated by dividing performance by RWL. Differences between groups with a
      lifting index < or =1, 1-3, and >3 were calculated for pain intensity, scores on
      the Roland Morris Disability Questionnaire (RMDQ) and work status. RESULTS: Men
      lifted on average 32.5 kg (SD 15.4) and women 18.8 kg (SD 7.8). RWL for this task
      was 12.8 kg. Mean difference between performance and RWL was 15.0 kg (SD 14.7;
      range -8.8 to 59.2). The Roland Morris Disability score of patients with a
      lifting index < or =1 was significantly lower than patients with a lifting index
      1-3 and >3. No difference in pain intensity and work status was found between
      groups. CONCLUSION: It was concluded that performance on the FCE floor-to-waist
      lifting task and RWL of the NIOSH for this task produce different safe lifting
      weights in individual patients with CLBP, which may result in contradictory
      recommendations about need for rehabilitation and return to work.

PMID- 16649008
TI  - Pregnancy outcomes in women with rheumatoid arthritis in Washington State.
AB  - OBJECTIVE: To determine whether rheumatoid arthritis (RA) is associated with
      increased adverse obstetric or neonatal outcomes. STUDY DESIGN AND SETTING:
      Washington State birth records and hospital discharge data between 1987 and 2001
      identified a cohort of women with rheumatoid arthritis and a comparison group of
      women without rheumatoid arthritis. Pregnancy and neonatal outcomes were compared
      using general linear models for common outcomes, calculating approximate relative
      risks and 95% confidence intervals. RESULTS: There were 243 women with rheumatoid
      arthritis and 2,559 controls. Infants of women with rheumatoid arthritis had
      increased risk of cesarean delivery (adjusted approximate relative risk,
      aRR=1.66, 95% CI (1.22, 2.26)), prematurity (aRR=1.78, 95% CI (1.21, 2.60)), and
      longer birth hospitalization (aRR=1.86, 95% CI (1.32, 2.60)) compared to those
      born to women without rheumatoid arthritis. CONCLUSIONS: We speculate that the
      increased risks for cesarean delivery, prematurity, and longer hospitalization at
      birth among infants born to women with rheumatoid arthritis may be due to the
      pathophysiologic changes associated with rheumatoid arthritis or medications used
      to treat the disease.

PMID- 16649014
TI  - [Recombinant activated factor VIIa for treatment of traumatic liver rupture].
AB  - Hepatic rupture after blunt abdominal trauma may lead to severe bleeding,
      depletion and consumption of clotting factors, with the risk of packing to defer
      the definitive operation. We report two cases of hepatic rupture after blunt
      trauma with intrahepatic hematoma and severe intraabdominal bleeding. In both
      cases the bleeding could be stopped by early intervention with recombinant
      activated factor VIIa (rFVIIa). In neither case was surgical intervention
      necessary and after 3 weeks both patients were released without complications.
      These cases demonstrate that the early therapy with a single dose of rFVIIa
      before the development of a hemostatic crisis is a therapeutic option in selected
      cases where surgical therapy of the bleeding is difficult and risky.

PMID- 16649017
TI  - Thrombin-like effect of an important green pit viper toxin, albolabrin: a
      bioinformatic study.
AB  - The green pit viper venom has a major effect on the hematological system.
      Clinical features of venomous snakebites vary from asymptomatic to fatal
      bleeding. The venom is found to have a thrombin-like effect in vitro. Here, the
      author performs a bioinformatic analysis on the green pit viper venom focusing on
      its thrombin-like effect. Sequence comparison between green pit viper venom,
      albolabrin and thrombin was performed. In addition, the author performed a search
      for other human proteins closely relating to the thrombin and created a multiple
      sequence alignment phylogenetic tree to present the family tree of the thrombin,
      albolabrin and those proteins recorded in the genomic database. In conclusion,
      the comparative sequence analysis between green pit viper venom and thrombin
      gives several identities. The reported relationship on the phylogenetic tree can
      match with the reported in vivo function of green pit viper. Explanations on the
      effect of green pit viper toxin on the hemostasis can be derived from this study.
      Furthermore, future researches based on the reported identities can be expected.

PMID- 16649023
TI  - Idiopathic infantile arterial calcification: clinical presentation, therapy and
      long-term follow-up.
AB  - Idiopathic infantile arterial calcification (IIAC) is a rare disease
      characterised by extensive depositions of hydroxyapatite in the internal elastic
      lamina of medium-sized and large arteries, frequently accompanied by
      periarticular calcifications. We report on three patients with various presenting
      signs and symptoms. Diagnostic imaging techniques and therapy with
      bisphosphonates will be discussed. For the first time long-term follow-up of up
      to 25 years will be reported.

PMID- 16649025
TI  - Severe outcome of children following trauma resulting from road accidents.
AB  - OBJECTIVE: The aim of the study was to determine the risk factors of a severe
      outcome for children severely injured [killed or with an Injury Severity Score
      (ISS)>or=16] in a road accident. MATERIALS AND METHODS: Casualties that occurred
      between 1996 and 2001 which involved children under 14 years of age were assessed
      in a population-based study based on data included in a French road trauma
      Registry. A severe traumatic brain injury (TBI) was defined as a head injury with
      an Abbreviated Injury Scale (AIS) severity score>or=3. A multivariate logistic
      regression was performed to quantify the risk of a "severe outcome" defined as
      death or an expected serious impairment 1 year later. RESULTS: The annual
      incidence of an ISS of 16+ was 7.7 per 100,000 children. Among the 126 severely
      injured children included in this study, 40 died (including 16 immediate deaths),
      and a severe outcome was expected for 54 of the 86 survivors. Children with an
      "isolated severe TBI" and those with "multiple injuries including TBI" were more
      likely to have a severe outcome than those who had an "isolated severe injury
      without TBI" (OR: 7.91; 95%CI: 1.43-43.77 and OR: 8.37; 95%CI: 1.52-46.13,
      respectively). Age was inversely linked to a severe outcome. The unprotected
      motor vehicle occupants (MVO) had an odds ratio of 7.56 (95%CI: 1.07-53.56)
      compared to the protected MVO. Only 30% of children who survived a severe TBI
      were admitted to rehabilitation. CONCLUSION: The mechanism of the injury, an
      injury pattern involving the head and a young age were associated with a severe
      outcome following a road accident. A majority of children severely injured were
      not referred to inpatient rehabilitation.

PMID- 16649026
TI  - Identifying children with sickle cell anaemia in a non-endemic country: age at
      diagnosis and presenting symptoms.

PMID- 16649027
TI  - Vitamin D intoxication and therapy with alendronate (case report and review of
      literature).

PMID- 16649028
TI  - Hypersensitivity to racecadotril: a case report.

PMID- 16649029
TI  - Muscular contributions to dynamic dorsoventral lumbar spine stiffness.
AB  - Spinal musculature plays a major role in spine stability, but its importance to
      spinal stiffness is poorly understood. We studied the effects of graded trunk
      muscle stimulation on the in vivo dynamic dorsoventral (DV) lumbar spine
      stiffness of 15 adolescent Merino sheep. Constant voltage supramaximal electrical
      stimulation was administered to the L3-L4 interspinous space of the multifidus
      muscles using four stimulation frequencies (2.5, 5, 10, and 20 Hz). Dynamic
      stiffness was quantified at rest and during muscle stimulation using a computer
      controlled testing apparatus that applied variable frequency (0.46-19.7 Hz)
      oscillatory DV forces (13-N preload to 48-N peak) to the L3 spinous process of
      the prone-lying sheep. Five mechanical excitation trials were randomly performed,
      including four muscle stimulation trials and an unstimulated or resting trial.
      The secant stiffness (k (y) = DV force/L3 displacement, kN/m) and loss angle
      (phase angle, deg) were determined at 44 discrete mechanical excitation
      frequencies. Results indicated that the dynamic stiffness varied 3.7-fold over
      the range of mechanical excitation frequencies examined (minimum resting k (y) =
      3.86 +/- 0.38 N/mm at 4.0 Hz; maximum k (y) = 14.1 +/- 9.95 N/mm at 19.7 Hz).
      Twenty hertz muscle stimulation resulted in a sustained supramaximal contraction
      that significantly (P < 0.05) increased k (y) up to twofold compared to rest
      (mechanical excitation at 3.6 Hz). Compared to rest, k (y) during the 20 Hz
      muscle stimulation was significantly increased for 34 of 44 mechanical excitation
      frequencies (mean increase = 55.1%, P < 0.05), but was most marked between 2.55
      and 4.91 Hz (mean increase = 87.5%, P < 0.05). For lower frequency, sub-maximal
      muscle stimulation, there was a graded change in k (y), which was significantly
      increased for 32/44 mechanical excitation frequencies (mean increase = 40.4%, 10
      Hz stimulus), 23/44 mechanical excitation frequencies (mean increase = 10.5%, 5
      Hz stimulus), and 11/44 mechanical excitation frequencies (mean increase = 4.16%,
      2.5 Hz stimulus) when compared to rest. These results indicate that the dynamic
      mechanical behavior of the ovine spine is modulated by muscle stimulation, and
      suggests that muscle contraction plays an important role in stabilizing the
      lumbar spine.

PMID- 16649030
TI  - Daily spinal mechanical loading as a risk factor for acute non-specific low back
      pain: a case-control study using the 24-Hour Schedule.
AB  - A case-control study was conducted to assess the daily loading of the spine as a
      risk factor for acute non-specific low back pain (acute LBP). Acute LBP is a
      benign, self-limiting disease, with a recovery rate of 80-90% within 6 weeks
      irrespective of the treatment type. Unfortunately, recurrence rates are high.
      Therefore, prevention of acute LBP could be beneficial. The 24-Hour Schedule
      (24HS) is a questionnaire developed to quantify physical spinal loading, which is
      regarded as a potential and modifiable risk factor for acute and recurrent low
      back pain. A total of 100 cases with acute LBP and 100 controls from a primary
      care setting were included. Cases and controls completed questionnaires regarding
      acute LBP status and potential risk factors. Trained examiners blinded to
      subjects' disease status (acute LBP or not) assessed spinal loading using the
      24HS. The mean difference of 24HS sum-scores between groups was statistically
      significant (P < 0.0001). After multivariate regression analysis, previous
      episode(s), the 24HS and the Nottingham Health Profile were associated with the
      presence of acute LBP. High 24HS scores, indicating longer and more intensive
      spinal loading in flexed position, are strongly associated with acute LBP.

PMID- 16649032
TI  - Interactions between the arbuscular mycorrhizal (AM) fungus Glomus intraradices
      and nontransformed tomato roots of either wild-type or AM-defective phenotypes in
      monoxenic cultures.
AB  - Monoxenic symbioses between the arbuscular mycorrhizal (AM) fungus Glomus
      intraradices and two nontransformed tomato root organ cultures (ROCs) were
      established. Wild-type tomato ROC from cultivar "RioGrande 76R" was employed as a
      control for mycorrhizal colonization and compared with its mutant line (rmc),
      which exhibits a highly reduced mycorrhizal colonization (rmc) phenotype.
      Structural features of the two root lines were similar when grown either in soil
      or under in vitro conditions, indicating that neither monoxenic culturing nor the
      rmc mutation affected root development or behavior. Colonization by G.
      intraradices in monoxenic culture of the wild-type line was low (<10%) but
      supported extensive development of extraradical mycelium, branched absorbing
      structures, and spores. The reduced colonization of rmc under monoxenic
      conditions (0.6%) was similar to that observed previously in soil. Extraradical
      development of runner hyphae was low and proportional to internal colonization.
      Few spores were produced. These results might suggest that carbon transfer may be
      modified in the rmc mutant. Our results support the usefulness of monoxenically
      obtained mycorrhizas for investigation of AM colonization and intraradical
      symbiotic functioning.

PMID- 16649033
TI  - Higher sensitivity in the detection of inflammatory brain lesions in patients
      with clinically isolated syndromes suggestive of multiple sclerosis using high
      field MRI: an intraindividual comparison of 1.5 T with 3.0 T.
AB  - The purpose of this study was to determine the sensitivities in the detection of
      inflammatory lesions in patients with clinically isolated syndromes suggestive of
      multiple sclerosis at 3.0 T and 1.5 T. MR imaging of 40 patients at both field
      strengths was performed in separate sessions including contiguous axial slices of
      T2 turbo spin-echo (T2 TSE), fluid-attenuated-inversion-recovery (FLAIR) and pre-
      and postcontrast T1 spin-echo (T1 SE). Inflammatory lesions > 3 mm in size were
      counted and categorized according to their anatomic location. Lesion conspicuity
      was assessed on a five-point scale. At 3.0 T, 13% more white matter lesions could
      be identified on the FLAIR sequence and on the T2 TSE sequence. Compared to 1.5 T
      7.5% more contrast-enhancing lesions were detected at 3.0 T. The higher detection
      rate at 3.0 T was significant for the infratentorial (p = 0.02) and juxtacortical
      (p < 0.01) region on the FLAIR as well as for the infratentorial (p = 0.03),
      juxtacortical (p = 0.02) and periventricular (p = 0.03) region on the T2 TSE
      sequence. The lesion conspicuity was significantly better at 3.0 T for FLAIR and
      T2 TSE sequences (p<0.01; p=0.01). In conclusion, high-field MRI at 3.0 T
      provides a significantly higher detection rate of inflammatory brain lesions
      especially in the infratentorial, juxtacortical and periventricular anatomic
      region.

PMID- 16649034
TI  - Fast prediction of protein domain boundaries using conserved local patterns.
AB  - We have found certain conserved motifs and secondary structural patterns present
      in the vicinity of interior domain boundary points (dbps) by a data-driven
      approach without any a priori constraint on the type and number of such features,
      and without any requirement of sequence homology. We have used these motifs and
      patterns to rerank the solutions obtained by the well-known domain guess by size
      (DGS) algorithm. We predict, overall, five solutions. The average accuracy of
      overall (i.e., top five) predictions by our method [domain boundary prediction
      using conserved patterns (DPCP)] has improved the average accuracy of the top
      five solutions of DGS from 71.74 to 82.88 %, in the case of two-continuous-domain
      proteins, and from 21.38 to 80.56 %, for two-discontinuous-domain proteins.
      Considering only the top solution, the gains in accuracy are from 0 to 72.74 %
      for two-continuous-domain proteins with chain lengths up to 300 residues, and
      from 0 to 62.85 % for those with up to 400 residues. In the case of discontinuous
      domains, top_min solutions (the minimum number of solutions required for
      predicting all dbps of a protein) of DPCP improve the average accuracy of DGS
      prediction from 12.5 to 76.3 % in proteins with chain lengths up to 300 residues,
      and from 13.33 to 70.84 % for proteins with up to 400 residues. In our validation
      experiments, the performance of DPCP was also found to be superior to that of
      domain identification from secondary structure element alignment (DomSSEA), the
      best method reported so far for efficient prediction of domain boundaries using
      predicted secondary structure. The average accuracies of the topmost solution of
      DomSSEA are 61 and 52 % for proteins with up to 300 residues and 400,
      respectively, in the case of continuous domains; the corresponding accuracies for
      the discontinuous case are 28 and 21 %.

PMID- 16649035
TI  - Boron nitride cages from B12N12 to B36N36: square-hexagon alternants vs boron
      nitride tubes.
AB  - The structures and stabilities of square-hexagon alternant boron nitrides (Bx Nx
      , x=12-36) vs their tube isomers containing octagons, decagons and dodecagons
      have been computed at the B3LYP density functional level of theory with the
      correlation-consistent cc-pVDZ basis set of Dunning. It is found that octagonal
      B20N20 and B24N24 tube structures are more stable than their square-hexagon
      alternants by 18.6 and 2.4 kcal mol(-1), respectively, while the square-hexagon
      alternants of other cages are more stable. Trends in stability as a function of
      cluster size are discussed.

PMID- 16649036
TI  - Sarcocystis sp. from white-fronted goose (Anser albifrons): cyst morphology and
      life cycle studies.
AB  - An experiment was carried out using three cubs of the arctic fox (Alopex
      lagopus). Twenty-five-day-old cubs were infected by feeding them with the leg
      muscles of the white-fronted goose (Anser albifrons) containing Sarcocystis sp.
      (cyst type III) cysts. Under the light microscope, the cysts were ribbon-shaped
      up to 4 mm long and up to 750 microm wide. On the surface of the wall (up to 2.4
      microm), they had teat- or finger-like villar protrusions. Ultrastructurally, the
      cyst wall was a type-9 with villar protrusions (up to 2.3 microm long) different
      in size. The 11.4x1.7 (10.0-13.5x1.5-2.5)microm cystozoites were almost straight
      and shuttle-shaped. The fox cubs started shedding typical 12.0x8.0 (10.0-12.8x6.8
      8.6)microm Sarcocystis sp. sporocysts on the 13th-14th days post-infection. The
      patent period lasted 19 days. The conclusion drawn was that the arctic fox (A.
      lagopus) can be one of the definitive hosts of Sarcocystis sp. (cyst type III)
      from the white-fronted goose.

PMID- 16649037
TI  - Incidence and risk factors for severe perineal laceration after vaginal delivery
      in Japanese patients.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of severe perineal
      lacerations defined as either third- or fourth-degree lacerations during normal
      spontaneous vaginal delivery and to evaluate potential risk factors in Japanese
      patients. MATERIALS AND METHODS: An electronic audit of the perinatal database at
      the Tama-Nagayama Hospital of Nippon Medical School and Yamaguchi Hospital from
      1997 through 2004 was completed. Singleton vaginal vertex deliveries were
      analyzed for potential risk factors using univariate and multivariate logistic
      regression analysis. RESULTS: From the database, 7,946 deliveries were
      identified, with 135 deliveries resulting in severe lacerations (1.7%). In the
      multivariate logistic regression analysis, severe lacerations were associated
      significantly with primiparous (odds ratio, 4.36; 95% CI, 2.17-9.57), oxytocin
      use (odds ratio, 2.19; 95% CI, 1.27-3.73), midline episiotomy (odds ratio, 4.68;
      95% CI, 2.09-11.55), forceps-assisted delivery (odds ratio, 7.11; 95% CI, 1.95
      20.59), vacuum-assisted delivery (odds ratio, 5.93; 95% CI, 3.38-10.36), and
      shorter attendant experience (odds ratio, 2.88; 95% CI, 1.12-9.81). CONCLUSIONS:
      The present study demonstrated that operator factors, such as midline episiotomy,
      oxytocin use, assisted delivery and attendant experience, are independent risk
      for severe perineal lacerations after vaginal delivery in Japanese patients. The
      results suggest that midline episiotomy and assisted vaginal delivery, especially
      forceps-assisted delivery should be avoided in patients who are being delivered
      of a first child whenever possible.

PMID- 16649038
TI  - Benign abdominal and pulmonary metastasizing leiomyoma of the uterus.
AB  - BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease in which the
      lung is described to be the most afflicted extrauterine organ. METHODS: We report
      of a 42-year-old African woman with a BML in the abdomen and lung who had
      undergone a hysterectomy for uterine leiomyoma 10 years ago. She was admitted to
      our hospital for investigation of a huge tumor mass in the pelvis consisting of
      multiple nodules in the abdomen and left lung. Assuming an advanced
      intraperitoneal malignancy was present, a 'palliative' limited tumor debulking
      and due to a tumor compressing the sigmoid a Hartmann's procedure was performed.
      RESULTS: The histopathologic examination showed a leiomyoma positive for estrogen
      receptor. Treatment was started with GnRH analoga. In the presence of a stable
      disease after 12 months, the patient underwent a re-laparotomy with a
      reanastomosis of the colon. Treatment was continued with GnRH analoga and the
      residual nodules have not increased in size during 36 months of follow-up.
      CONCLUSIONS: The review of the literature supports the concept that the primary
      tumor of BML is located in the uterus and that leiomyomas in the uterus can
      metastasize leading via hematogenous spread to BML. However, the origin of the
      tumor remains controversial.

PMID- 16649039
TI  - Bladder stone: uncommon cause of mechanical dystocia.
AB  - Bladder stone can exceptionally cause an obstetrical dystocia. A combined
      procedure of cesarean section with a cystolithotomy is the most advocated
      attitude. The authors reported a rare case of mechanical dystocia caused by a
      bladder stone in a 27 year-old multiparous women. The diagnosis was suspected
      during labor and a vaginal examination revealed a large firm mass in the anterior
      vagina wall. This mass was responsible for an obstruction of the pelvis requiring
      a cesarean section. A cystotomy was performed intraoperatively and a bladder
      stone weighing 130 g and measuring 8 x 6 x 4 cm(3) was extracted. The
      postoperative course was uneventful.

PMID- 16649040
TI  - Effects of aspirin on placenta and perinatal outcomes in patients with poor
      obstetric history.
AB  - OBJECTIVE: The aim of this study was to compare a low-dose aspirin treatment on
      placental and perinatal effects in the patients with poor obstetric history such
      as preeclampsia, intrauterine growth retardation (IUGR) in previous pregnancy.
      STUDY DESIGN: This retrospective study of 86 pregnant women was conducted between
      April 2002 and June 2005. In this study period 364 placentas were examined and
      the patients with poor obstetric history such as IUGR and preeclampsia were
      selected. Then the patients were assigned to three groups; group 1 (n = 30) was
      composed of women with no risk in previous pregnancy; group 2 (n = 27) was
      composed of patients with poor obstetric history (e.g., preeclampsia, IUGR) who
      were treated with aspirin and patients in group 3 (n = 29) had poor obstetric
      history without any treatment (patients who were started to follow-up after 14
      weeks of gestation). Patients in group 2 were treated with a low-dose aspirin (80
      mg/day) as soon as a urinary pregnancy test was positive. Treatment was usually
      stopped at 34 completed weeks of gestation. On histopathologic examination of the
      placenta, uteroplacental vascular pathologic features and secondary villous
      damage (such as fibrinoid necrosis of desidual vessels, villous infarct, severely
      increased villous fibrosis, severely increased syncytiotrophoblast knotting,
      obliteration of the vessel lumen, severely increased villous hypervascularity)
      and also lesions involving coagulation (such as excessive perivillous fibrin
      deposition, multiple occlusive thrombi in uteroplacental vessels, avascular villi
      ) were examined. RESULTS: There were no significant differences between the
      groups with respect to maternal age, body mass index at the first trimester and
      delivery. Also there were no significant differences among groups with respect to
      placental weight, fetal height, weight, gestational week, umbilical artery pH,
      pO2, pCO2 and base excess status. The incidences of preeclampsia were 3.3, 7.4,
      6.8% and the incidences of IUGR were 6.7, 11.1, 6.8% in the groups, respectively
      (P > 0.05 for both). Although the percentages of all pathologic findings were
      higher in groups 2 and 3, these differences were not statistically important.
      CONCLUSION: When low-dose aspirin is taken, starting at the beginning of
      pregnancy in patients with poor obstetric history, there are still high
      frequencies of uteroplacental vascular and related villous lesions persisted on
      placental bed. Also it has no beneficial effects on perinatal outcomes in these
      patients.

PMID- 16649041
TI  - Uterine arteriovenous malformation following medical termination of pregnancy: a
      case report.
AB  - A 21-year-old nulliparous patient presented with heavy vaginal bleeding following
      medical termination of pregnancy. She dropped her haemoglobin level quickly. An
      MRI scan showed the presence of serpiginous vessels within the myometrium. The
      patient was successfully treated by arterial embolisation.

PMID- 16649043
TI  - Solitary myofibroma of the lumbar vertebra: adult case.
AB  - We present the first known adult case of solitary myofibroma of bone, which
      affected a lumbar vertebra in a 33-year-old male. Radiography identified a purely
      lytic lesion with a sclerotic rim in the right pedicle of L1. CT showed an
      expansile lytic lesion with a sclerotic rim. MRI of the lesion revealed an
      isointense signal on T1-weighted images, an inhomogeneously hyperintense signal
      on T2-weighted images, and marked enhancement with gadolinium. Pathological study
      showed a mixed picture of nodular proliferation of spindle-shaped myoid cells and
      hemangiopericytomatous proliferation of short spindle/small round cells. The
      tumor cells were immunoreactive for smooth muscle actin and immunonegative for
      desmin. This case of solitary myofibroma of bone is exceptionally rare because of
      its occurrence in an adult older than 20 years of age and its location at an
      extra-craniofacial site.

PMID- 16649044
TI  - LeMAN4 endo-beta-mannanase from ripe tomato fruit can act as a mannan
      transglycosylase or hydrolase.
AB  - Mannan transglycosylases are cell wall enzymes able to transfer part of the
      mannan polysaccharide backbone to mannan-derived oligosaccharides (Schroder et
      al. in Planta 219:590-600, 2004). Mannan transglycosylase activity was purified
      to near homogeneity from ripe tomato fruit. N-terminal sequencing showed that the
      dominant band seen on SDS-PAGE was identical to LeMAN4a, a hydrolytic endo-beta
      mannanase found in ripe tomato fruit (Bewley et al. in J Exp Bot 51:529-538,
      2000). Recombinant LeMAN4a protein expressed in Escherichia coli exhibited both
      mannan hydrolase and mannan transglycosylase activity. Western analysis of ripe
      tomato fruit tissue using an antibody raised against tomato seed endo-beta
      mannanase revealed four isoforms present after 2D-gel electrophoresis in the pH
      range 6-11. On separation by preparative liquid isoelectric focussing, these
      native isoforms exhibited different preferences for transglycosylation and
      hydrolysis. These results demonstrate that endo-beta-mannanase has two
      activities: it can either hydrolyse mannan polysaccharides, or in the presence of
      mannan-derived oligosaccharides, carry out a transglycosylation reaction. We
      therefore propose that endo-beta-mannanase should be renamed mannan
      transglycosylase/hydrolase, in accordance with the nomenclature established for
      xyloglucan endotransglucosylase/hydrolase. The role of endo-acting mannanases in
      modifying the structure of plant cell walls during cell expansion, seed
      germination and fruit ripening may need to be reinterpreted in light of their
      potential action as transglycosylating or hydrolysing enzymes.

PMID- 16649052
TI  - Late complications of circumcision in Iran.
AB  - Today, circumcision is the most commonly performed surgical procedure worldwide.
      Early and late complications may occur due to circumcision. To find the
      prevalence of late complications of circumcision, we studied 3,205 elementary
      school boys aged 6-12 years in 2002. All of them were Iranian and Muslim. Nearly
      3,125 of the boys have been circumcised. Most of the boys (2,214 boys) had been
      circumcised after 2 years of age. Moreover, most of them were operated by
      traditional circumcisers (43.49%). Late complications (7.39%) were reported in
      231 boys. Excessive residual foreskin was seen in 113 children (3.6%). Excessive
      removal of skin was detected in 42 boys (1.3%), meatal stenosis in 29 boys
      (0.9%), granoloma in 22 boys (0.7%), penile rotation in 17 boys (0.5%), and 8
      boys had secondary chordee (0.2%). The complication rate was not different
      between the neonatal circumcision and older groups. We suggested that
      circumcision should only be performed in medical institutions by suitably trained
      specialists.

PMID- 16649053
TI  - Umbilical hernia repair in children: is pressure dressing necessary.
AB  - The use of pressure dressing to cover the sutured surgical wound is usually
      considered a routine conclusion to the repair of umbilical hernias in children.
      The wound is usually left dressed for a minimum of 5-7 days. The main purpose of
      pressure dressing is prevention of a hematoma formation. The aim of this study
      was to compare the surgical outcome after umbilical hernia repair in children
      when the wounds were covered using pressure dressing or left exposed without
      dressing after the completion of wound closure. Ninety-six patients with
      umbilical hernia repair were prospectively randomized to receive pressure
      dressing (n=52) or have their wounds left exposed without any dressing (n=44)
      after the completion of wound closure. None of the hernias were huge umbilical
      hernia and none required an umbilicoplasty. In the group who received pressure
      dressing, one patient developed wound infection 1.9% while no patients developed
      wound infection in the group who had their wounds exposed without any dressing.
      In children, there was no significant difference in terms of wound infection,
      hematoma or seroma formation and recurrence rate after applying pressure dressing
      or leaving the surgical wounds exposed without any dressing after completion of
      wound closure. Pressure dressing after umbilical hernia repair may be
      unnecessary.

PMID- 16649054
TI  - Primary peritoneal drainage in necrotising enterocolitis: an 18-year experience.
AB  - Primary peritoneal drainage (PPD) was initially introduced as a method for the
      pre-operative resuscitation of critically ill infants with complicated
      necrotising enterocolitis (NEC). Some have recommended it as definitive strategy
      for a select group of extremely low birth weight babies. The role of laparotomy
      in neonates who do not respond to initial PPD has also been challenged. With this
      background, we analysed our experience with the use of PPD in babies with NEC
      over an 18-year period. We retrospectively reviewed all patients with NEC who had
      PPD as their initial surgical management over an 18-year period. A total of 122
      babies with NEC were treated surgically, of whom 42 had PPD as the initial
      procedure. There were 28 survivors (67%) in the PPD group, of whom 7 recovered
      without laparotomy. Twenty-nine infants (69%) had a good clinical response to PPD
      with 80% (23/29) survival, compared to a 27% survival (3/11) in those who did not
      respond to drainage. Six patients underwent rescue laparotomy after a poor
      response to PPD and three of these survived. Six of the 28 pts who underwent
      laparotomy had isolated intestinal perforation and their clinical characteristics
      were no different from those with typical NEC. PPD is a useful option in the
      management of complicated NEC. It is difficult to recognise with certainty those
      infants who will not require a subsequent laparotomy and therefore we do not
      support the concept of PPD solely as a definitive strategy. The response to PPD
      is a good prognostic indicator for ultimate survival. Despite a low salvage rate
      of 27% in non-responders compared to 80% in responders, there is a role for early
      laparotomy for those infants who do not respond to PPD.

PMID- 16649057
TI  - Suicidal erythrocyte death occurs in the hemolytic uremic syndrome.

PMID- 16649058
TI  - Mutation analysis of 218 Chinese patients with Wilson disease revealed no
      correlation between the canine copper toxicosis gene MURR1 and Wilson disease.
AB  - Wilson disease (WD) is the most common disorder resulting in hepatic copper
      overload. A similar form of copper-associated cirrhosis caused by mutations of
      the canine copper toxicosis MURR1 gene is also observed in Bedlington terriers.
      Recent studies indicate that MURR1 might influence human copper metabolism and
      the clinical presentations of WD. However, the correlation between the MURR1 gene
      and the Chinese patients with WD has not been reported. In the present study, all
      three exons of the MURR1 gene including the intron-exon boundaries were directly
      sequenced in 120 unrelated healthy Chinese and 218 unrelated Chinese patients
      with WD. No mutations were detected in coding and splice site sequence in the
      human MURR1 gene. A novel polymorphism 3'+119T-->A in the 3' untranslated region
      (UTR) was identified in three healthy individuals and four patients with two
      disease-causing mutations in the ATP7B gene and a great diversity of clinical
      presentations. Of the ATP7B mutations reported here, Gly1268Arg is a novel one.
      Also, the previously described nucleotide change IVS2+63C-->G was detected in
      31.66% of normal chromosomes and 26.15% of WD chromosomes. The results have
      indicated that there is no correlation between MURR1 and WD in the Chinese
      population.

PMID- 16649059
TI  - MDCT findings in neuroendocrine carcinoma of the gallbladder: case report.
AB  - Neuroendocrine tumors are commonly seen in the gastrointestinal tract, but they
      are extremely rare in the gallbladder. In this study, sonographic and
      multidetector-row computed tomographic findings of a patient with neuroendocrine
      tumors of the gallbladder are presented.

PMID- 16649055
TI  - Pharmacology of P2X channels.
AB  - Significant progress in understanding the pharmacological characteristics and
      physiological importance of homomeric and heteromeric P2X channels has been
      achieved in recent years. P2X channels, gated by ATP and most likely trimerically
      assembled from seven known P2X subunits, are present in a broad distribution of
      tissues and are thought to play an important role in a variety of physiological
      functions, including peripheral and central neuronal transmission, smooth muscle
      contraction, and inflammation. The known homomeric and heteromeric P2X channels
      can be distinguished from each other on the basis of pharmacological differences
      when expressed recombinantly in cell lines, but whether this pharmacological
      classification holds true in native cells and in vivo is less well-established.
      Nevertheless, several potent and selective P2X antagonists have been discovered
      in recent years and shown to be efficacious in various animal models including
      those for visceral organ function, chronic inflammatory and neuropathic pain, and
      inflammation. The recent advancement of drug candidates targeting P2X channels
      into human trials, confirms the medicinal exploitability of this novel target
      family and provides hope that safe and effective medicines for the treatment of
      disorders involving P2X channels may be identified in the near future.

PMID- 16649060
TI  - Computed tomography of gastrocolic ligament: involvement in malignant tumors of
      the stomach.
AB  - BACKGROUND: This study investigated computed tomographic (CT) features and
      anatomic bases of gastrocolic ligament involvement in malignant neoplasms of the
      stomach. METHODS: We retrospectively reviewed CT scans of 34 patients known to
      have gastric malignant neoplasm and gastrocolic ligament involvement. Emphasis
      was placed on direct invasion, lymph node metastasis, and omental seeding.
      RESULTS: CT manifestations of gastrocolic ligament involvement included direct
      invasion (38.2%, 13 of 34), enlargement of lymph nodes (50%, 17 of 34), "smudged"
      appearance (26.5%, nine of 34), "omental caking" (5.9%, two of 34), cystic mass
      (2.9%, one of 34), and varices of the omentum (2.9%, one of 34). We also found
      that gastric carcinoma and gastrointestinal stromal tumor invaded the transverse
      colon through the gastrocolic ligament in six patients (17.6%, six of 34).
      CONCLUSION: CT scan is useful for detecting gastrocolic ligament involvement in
      gastric malignant neoplasm. The imaging features consist of a mass sign,
      enlargement of lymph nodes, smudged appearance, omental caking, and so on.
      Gastric malignant neoplasm also may involve the transverse colon through the
      gastrocolic ligament.

PMID- 16649061
TI  - Molecular diversity of nifH genes from bacteria associated with high arctic dwarf
      shrubs.
AB  - Biological nitrogen fixation is the primary source of new N in terrestrial arctic
      ecosystems and is fundamental to the long-term productivity of arctic plant
      communities. Still, relatively little is known about the nitrogen-fixing microbes
      that inhabit the soils of many dominant vegetation types. Our objective was to
      determine which diazotrophs are associated with three common, woody, perennial
      plants in an arctic glacial lowland. Dryas integrifolia, Salix arctica, and
      Cassiope tetragona plants in soil were collected at Alexandra Fiord, Ellesmere
      Island, Canada. DNA was extracted from soil and root samples and a 383-bp
      fragment of the nifH gene amplified by the polymerase chain reaction. Cloned
      genotypes were screened for similarity by restriction fragment length
      polymorphism (RFLP) analysis. Nine primary RFLP phylotypes were identified and 42
      representative genotypes selected for sequencing. Majority of sequences (33) were
      type I nitrogenases, whereas the remaining sequences belonged to the divergent,
      homologous, type IV group. Within the type I nitrogenases, nifH genes from
      posited members of the Firmicutes were most abundant, and occurred in root and
      soil samples from all three plant species. nifH genes from posited Pseudomonads
      were found to be more closely associated with C. tetragona, whereas nifH genes
      from putative alpha-Proteobacteria were more commonly associated with D.
      integrifolia and S. arctica. In addition, 12 clones likely representing a unique
      clade within the type I nitrogenases were identified. To our knowledge, this
      study is the first to report on the nifH diversity of arctic plant-associated
      soil microbes.

PMID- 16649062
TI  - Characterization of bacterial community structure on a weathered pegmatitic
      granite.
AB  - This study exploited the contrasting major element chemistry of a pegmatitic
      granite to investigate mineralogical influences on bacterial community structure.
      Intact crystals of variably weathered muscovite, plagioclase, K-feldspar, and
      quartz were extracted, together with whole-rock granite. Environmental scanning
      electron microscopy revealed a diversity of bacterial structures, with rods and
      cocci clearly visible on surfaces of all mineral types. Bacterial automated
      ribosomal intergenic spacer analysis was used to generate a ribotype profile for
      each mineral. A randomization test revealed that community fingerprints differed
      between different mineral types, whereas canonical correspondence analysis (CCA)
      showed that mineral chemistry affected individual bacterial ribotypes. CCA also
      revealed that Al, Si, and Ca had a significant impact on bacterial community
      structure within the system, which contrasts with the finding within fungal
      communities that although Al and Si also had a significant impact, K rather than
      Ca was important. The bacterial populations associated with different minerals
      were different. Members of each of these populations were found almost
      exclusively on a single mineral type, as was previously reported for fungal
      populations. These results show that bacterial community structure was driven by
      the chemical composition of minerals, indicating selective pressure by individual
      chemical elements on bacterial populations in situ.

PMID- 16649066
TI  - ACE-inhibition for secondary prevention of cardiovascular events--should we
      change our recommendation after PEACE?

PMID- 16649067
TI  - Dynamics of outgrowth in a continuum model of neurite elongation.
AB  - Neurite outgrowth (dendrites and axons) should be a stable, but easily regulated
      process to enable a neuron to make its appropriate network connections during
      development. We explore the dynamics of outgrowth in a mathematical continuum
      model of neurite elongation. The model describes the construction of the internal
      microtubule cytoskeleton, which results from the production and transport of
      tubulin dimers and their assembly into microtubules at the growing neurite tip.
      Tubulin is assumed to be largely synthesised in the cell body from where it is
      transported by active mechanisms and by diffusion along the neurite. It is argued
      that this construction process is a fundamental limiting factor in neurite
      elongation. In the model, elongation is highly stable when tubulin transport is
      dominated by either active transport or diffusion, but oscillations in length may
      occur when both active transport and diffusion contribute. Autoregulation of
      tubulin production can eliminate these oscillations. In all cases a stable steady
      state length is reached, provided there is intrinsic decay of tubulin. Small
      changes in growth parameters, such as the tubulin production rate, can lead to
      large changes in length. Thus cytoskeleton construction can be both stable and
      easily regulated, as seems necessary for neurite outgrowth during nervous system
      development.

PMID- 16649068
TI  - Spike propagation in dendrites with stochastic ion channels.
AB  - We investigate the effects of the stochastic nature of ion channels on the
      faithfulness, precision and reproducibility of electrical signal transmission in
      weakly active, dendritic membrane under in vitro conditions. The properties of
      forward and backpropagating action potentials (BPAPs) in the dendritic tree of
      pyramidal cells are the subject of intense empirical work and theoretical
      speculation (Larkum et al., 1999; Zhu, 2000; Larkum et al., 2001; Larkum and Zhu,
      2002; Schaefer et al., 2003; Williams, 2004; Waters et al., 2005). We numerically
      simulate the effects of stochastic ion channels on the forward and backward
      propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed
      layer 5 pyramidal neuron. We report that in most instances there is little
      variation in timing or amplitude for a single BPAP, while variable
      backpropagation can occur for trains of action potentials. Additionally, we find
      that the generation and forward propagation of dendritic Ca(2+) spikes are
      susceptible to channel variability. This indicates limitations on computations
      that depend on the precise timing of Ca(2+) spikes.

PMID- 16649071
TI  - A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene
      enhances CTL response and anti-tumor activity.
AB  - The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated
      cancer cells and are responsible for their malignant transformation. Therefore,
      HPV E6 and E7 are ideal target antigens for developing vaccines and
      immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has
      been demonstrated that codon optimization of the HPV-16 E7 gene resulted in
      highly efficient translation of E7 and increased the immunogenicity of E7
      specific DNA vaccines. Since vaccines targeting E6 also represent an important
      strategy for controlling HPV-associated lesions, we developed a codon-optimized
      HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T
      cell immune responses as well as the protective and therapeutic anti-tumor
      effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human
      embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly
      efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt
      significantly enhanced E6-specific CD8+ T cell immune responses in C57BL/6 mice.
      Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and
      therapeutic antitumor effects against challenge with E6-expressing tumor cell
      line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a
      promising strategy for improving the potency of prophylactic and therapeutic HPV
      vaccines with potential clinical implications.

PMID- 16649072
TI  - Mortality excess in individuals with elevated IgA anti-transglutaminase
      antibodies: the KORA/MONICA Augsburg cohort study 1989-1998.
AB  - OBJECTIVES: Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase
      (tTG) are commonly used for screening and diagnosing of celiac disease. We
      examined the hypothesis that elevated IgA anti-tTG antibodies were associated
      with higher all-cause mortality risk. METHODS: The cohort, 2333 men and 2300
      women, was based on the follow-up of participants of a representative population
      based survey in Southern Germany (KORA/MONICA Augsburg project) conducted in 1989
      1990. The endpoint for the vital status with cause of death was the year 1998.
      The sera drawn at baseline and stored at -80 degrees C, were recently screened
      with an IgA enzyme-linked immunosorbent assay (ELISA) using human recombinant
      tTG. Age-standardized mortality rates and age-adjusted hazard ratios were
      calculated. RESULTS: From the 4633 sera analyzed, 63 had an IgA anti-tTG
      concentration>or=7 AU/ml. Of these 63 individuals, 15 died between 1989 and 1998.
      The age-adjusted hazard ratio (HRa) of all-cause mortality was 1.86 (95% CI: 1.01
      3.41) and 3.92 (95% CI: 1.44-10.71) for men and women, respectively. The excess
      of cancer mortality was even higher with an HR(a) of 2.47 (95% CI: 0.89-6.83) in
      men and of 6.65 (95% CI: 2.04-21.63) in women. CONCLUSIONS: Individuals with
      elevated IgA anti-tTG antibodies had a highly increased mortality risk,
      particularly due to cancer. New studies are necessary to clarify if this
      increased risk is due to undiagnosed celiac disease or/and if this elevated IgA
      anti-tTG antibodies level is a marker of serious diseases like cancer, chronic
      liver disease or end-stage heart failure.

PMID- 16649073
TI  - Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma.
AB  - The uPA/uPAR system is involved in tumour progression and metastasis of a variety
      of cancers. Previously, we have shown that increased expression of urokinase
      plasminogen activator (uPA) correlated with malignancy grade in certain sarcomas.
      A study looking at in vivo inhibition of this system has not been done to date
      for osteosarcoma. More recently, this laboratory developed a clinically relevant
      mouse model where intratibial injection of UMR106-01 cells resulted in the
      development of osteosarcoma and lung metastases. Expression of uPA and its
      receptor (uPAR) were localised to the invading front of the tumours. Pulmonary
      metastasis is a predominant feature of the disease and is the major cause of
      death in patients. In the present study, the effects of down-regulating uPAR were
      observed in vitro and in vivo. UMR106-01 cells were transfected with either
      antisense-uPAR or vector control plasmids. Two antisense clones, exhibiting uPAR
      downregulation, demonstrated decreased adhesion, migration and invasion in cell
      based assays in vitro (P<0.05). Cellular proliferation was not affected by uPAR
      downregulation. In vivo, a marked reduction of 80% in tibial tumour volumes
      (P<0.05), and total inhibition of pulmonary metastases were observed in mice
      injected with the more potent of the antisense clones. This study proves
      seminally the usefulness of uPAR antisense in curbing the growth and spread of
      osteosarcoma.

PMID- 16649074
TI  - Dedicated calibration formulas permit correction of differences between
      measurements by different IVUS devices as demonstrated in atherosclerotic human
      coronary arteries in vitro.
AB  - Serial intravascular ultrasound (IVUS) measurements of coronary vessel dimensions
      are major endpoints of studies focusing on pharmacological interventions,
      efficiency of drug eluting stents, and vascular remodeling. In serial studies
      measurement variability among different IVUS devices may cause substantial
      misinterpretation and error. We analyzed 33 human coronary plaques in vitro using
      two different IVUS systems (mechanical IVUS system with a 40 MHz Atlantis SR
      catheter; solid-state electronic IVUS system with a 20 MHz Invision catheter) and
      repeatedly measured the total vessel, lumen, and plaque + media cross-sectional
      area and plaque burden (plaque + media area divided by total vessel area).
      Between the "raw" measurements made by the two devices, there was a significant
      difference for both plaque + media area (2.35+/-1.86 mm(2), P < 0.01) and plaque
      burden (5.39+/-3.68%, P < 0.05). Measurements were then corrected by use of
      recently introduced calibration formulas; as a result the differences decreased
      significantly for all IVUS parameters measured ( P < 0.0001). After correction,
      the remaining differences between the corrected mechanical and solid-state IVUS
      measurements similar to differences between repeated measurements with the same
      IVUS device (i.e., the intraobserver variability). Thus, in serial studies the
      use of different IVUS devices at index and follow-up procedure may introduce a
      substantial error as a result of system-related differences. The application of
      dedicated calibration formulas allows for correction for these differences by
      decreasing such differences to the level of intraobserver variability.

PMID- 16649075
TI  - Narratives about illness and medication: a neglected theme/new methodology within
      pharmacy practice research. Part I: conceptual framework.
AB  - This paper sets out a conceptual and theoretical framework relevant to developing
      research in the area of narratives about medication. Drawing on an understanding
      and critique of the psychological, sociological and anthropological literature in
      the area of patients' narratives about health and illness, we argue that pharmacy
      practice researchers need to acknowledge and appreciate the insights that can
      come from engaging with narrative. We provide a critique of the current
      limitations of pharmacy practice research as applied to patient's use of
      medication and suggest that an appreciation of narrative might provide another
      window on the world of patients' experiences.

PMID- 16649076
TI  - A review of rapid methods for the analysis of mycotoxins.
AB  - An overview is presented of the analysis of mycotoxins by rapid methods such as:
      enzyme linked immunosorbent assay (ELISA); flow through membrane based
      immunoassay; immunochromatographic assay; fluorometric assay with immunoaffinity
      clean-up column or with a solid phase extraction clean-up column; and
      fluorescence polarization method. These methods are currently commercially
      available and are reliable, rapid methods. This review focuses on the basic
      principle of each rapid method as well as advantages and limitations of each
      method. Additionally, we address other emerging technologies of potential
      application in the analysis of mycotoxins.

PMID- 16649077
TI  - Geographic distribution of human blastomycosis cases in Milwaukee, Wisconsin,
      USA: association with urban watersheds.
AB  - Most studies of endemic blastomycosis and outbreaks have involved rural areas.
      Case homesites in rural Northern Wisconsin have been associated with waterways
      and sand soils. ARC-GIS was used to geocode addresses and to observe geographic
      features of homesites from 45 State-mandated reports of human blastomycosis in
      urban Milwaukee County, Southeastern Wisconsin 2000-2004. Each case property was
      directly observed, and houses and duplexes (N = 38) were compared with 151 same
      street control homesites. Categorical data was analyzed using a chi-square or
      Fisher's exact test; continuous variables by Kruskal-Wallis test. One case
      cluster was seen on Milwaukee's North side where the estimated annual incidence
      was 2.8/100,000 compared to 0.96/100,000 for the entire county. Cases were less
      common in the most urbanized watersheds (0.49/100,000/yr) versus Lake Michigan
      shores (0.85) versus remaining three open watersheds (1.4) [P<0.01]. Case
      homesites averaged 1067 m to waterways and none were on sand soils. (Comparison
      is made to a Northern Wisconsin community where case homesites averaged 354 m to
      waterways, 24/25 were on sand soils and annual incidence was 74/100,000.) No
      unique features of case homesites were identified in Milwaukee County. In this
      urban area of Wisconsin, relatively low incidence rates may be explained, in
      part, by lower density of inland waterways and lack of sand soils, however,
      blastomycosis cases appear to be associated with open watersheds.

PMID- 16649078
TI  - A polyketide synthase gene required for biosynthesis of the aflatoxin-like toxin,
      dothistromin.
AB  - Dothistromin is a polyketide toxin, produced by a fungal forest pathogen, with
      structural similarity to the aflatoxin precursor versicolorin B. Biochemical and
      genetic studies suggested that there are common steps in the biosynthetic
      pathways for these metabolites and showed similarities between some of the genes.
      A polyketide synthase gene (pksA) was isolated from dothistromin-producing
      Dothistroma septosporum by hybridization with an aflatoxin ortholog from
      Aspergillus parasiticus. Inactivation of this gene in D. septosporum resulted in
      mutants that could not produce dothistromin but that could convert exogenous
      aflatoxin precursors, including norsolorinic acid, into dothistromin. The mutants
      also had reduced asexual sporulation compared to the wild type. So far four other
      genes are known to be clustered immediately alongside pksA. Three of these (cypA,
      moxA, avfA) are predicted to be orthologs of aflatoxin biosynthetic genes. The
      other gene (epoA), located between avfA and moxA, is predicted to encode an
      epoxide hydrolase, for which there is no homolog in either the aflatoxin or
      sterigmatocystin gene clusters. The pksA gene is located on a small chromosome of
      approximately 1.3 Mb in size, along with the dothistromin ketoreductase (dotA)
      gene.

PMID- 16649079
TI  - Carbon requirements of some nematophagous, entomopathogenic and mycoparasitic
      hyphomycetes as fungal biocontrol agents.
AB  - Thirty-three carbon sources were evaluated for their effects on spore
      germination, hyphal growth and sporulation of 11 fungal biocontrol agents, i.e.
      the nematophagous fungi Paecilomyces lilacinus, Pochonia chlamydosporia,
      Hirsutella rhossiliensis, H. minnesotensis and Arkansas Fungus 18, the
      entomopathogenic fungi Lecanicillium lecanii, Beauveria bassiana and Metarhizium
      anisopliae, and the mycoparasitic fungus Trichoderma viride. Variations in carbon
      requirements were found among the fungal species or strains tested. All strains
      studied except for T. viride grew on most carbon sources, although B. bassiana
      had more fastidious requirements for spore germination. Monosaccharides and
      disaccharides were suitable for fungal growth. For most isolates, D-glucose, D
      mannose, sucrose and trehalose were superior to pectin and soluble starch among
      the polysaccharides and lactic acid among the organic acids. Both ethanol and
      methanol could accelerate growth of most isolates but not biomass. D-mannose, D
      fructose and D-xylose were excellent carbon sources for sporulation, while D
      glucose, sucrose, cellobiose, trehalose, chitin, dextrin, gelatin and lactic acid
      were better for some isolates. Neither sorbic acid nor linoleic acid could be
      utilized as a single carbon source. These findings provided a better
      understanding of the nutritional requirements of different fungal biocontrol
      agents that can benefit the mass production process.

PMID- 16649080
TI  - Detection of two fungal biocontrol agents against root-knot nematodes by RAPD
      markers.
AB  - The strain ZK7 of Pochonia chlamydosporia var. chlamydosporia and IPC of
      Paecilomyces lilacinus are highly effective in the biological control against
      root-knot nematodes infecting tobacco. When applied, they require a specific
      monitoring method to evaluate the colonization and dispersal in soil. In this
      work, the randomly amplified polymorphic DNA (RAPD) technique was used to
      differentiate between the two individual strains and 95 other isolates, including
      isolates of the same species and common soil fungi. This approach allowed the
      selection of specific fragments of 1.2 kb (Vc1200) and 2.0 kb (Vc2000) specific
      for ZK7, 1.4 kb (P1400) and 0.85 kb (P850) specific for IPC, using the random
      Primers OPL-02, OPD-05, OPD-05 and OPC-11, respectively. These fragments were
      cloned, sequenced, and used to design sequence-characterized amplification region
      (SCAR) primers specific for the two strains. In classical polymerase chain
      reaction (PCR), with serial dilution of ZK7 and IPC pure culture DNAs template,
      the detection limits of these oligonucleotide SCAR-PCR primers were found to be
      10, 1000, 500, 100 pg, respectively. In the dot blotting, digoxigenin (DIG)
      labeled amplicons from these four primers specifically recognized the
      corresponding fragments in the DNAs template of these two strains. The detection
      limit of these amplicons were 0.2, 0.2, 0.5, 0.5 mug, respectively.

PMID- 16649081
TI  - Aspergillosis in Larus cachinnans micaellis: survey of eight cases.
AB  - Avian aspergillosis is reported in several avian species, with Aspergillus
      fumigatus as the main aetiological agent. Predisposing factors such as
      starvation, thermal stress, migratory stress, primary infectious disease or
      toxicosis may play a role. Eight cases of disseminated aspergillosis in free
      ranging seagulls sheltered at C.R.U.M.A. (Centro Recupero Uccelli Marini e
      Acquatici, Livorno, Italy) with different clinical histories are presented. The
      infection was demonstrated by cultural and histological methods from lesions of
      all birds, and the presence of airborne A. fumigatus viable elements ranging from
      450 to 525 CFU/m(3) inside and outside the shelter by means of a surface air
      sampler (SAS) Super-90 was also assessed. The role of this fungal species as an
      opportunistic factor in the captivity of seagulls is considered and some control
      measures, such as a clean and stress free environment and the use of antifungal
      drugs are suggested.

PMID- 16649082
TI  - Endophytic colonisation of opium poppy, Papaver somniferum, by an
      entomopathogenic Beauveria bassiana strain.
AB  - Beauveria bassiana strain EABb 04/01-Tip isolated from stem-borer larvae of
      Timaspis papaveris (Hymenoptera: Cynipidae), a serious pest of opium poppy in
      Spain, was shown to be able to become established endophytically in this
      pharmaceutical crop. Microbiological, molecular and light and electron
      microscopic methods were used to study fungal colonisation and to describe its
      mode of penetration. After inoculation with a foliar spray of conidia,
      microbiological methods showed 100% of plants examined 24, 48, 72 and 144 h after
      treatment to be colonised endophytically by the fungus, although the percentage
      of previously surface sterilised leaf pieces showing fungal growth was 100% at 24
      and 48 h, and 80 and 75% at 72 and 144 h after treatment, respectively. The
      fungus was also observed in leaf pieces obtained from newly formed leaves,
      indicating that it could spread from treated leaves to leaves formed after fungal
      application. For molecular studies, a polymerase chain reaction (PCR) protocol
      was used to amplify the ITS1-5.8S-ITS2 regions of the rDNA of the plant and the
      fungus. This procedure allowed the detection of the fungus on the surface of the
      leaves and also endophytically, but only at 72 h after treatment. A nucleotide
      BLAST search revealed that the ITS1-5.8S-ITS2 sequence of strain EABb 04/01-Tip
      showed 100% homology with a similar sequence from Cordyceps bassiana. SEM images
      revealed that although numerous conidia were observed on the leaf surface, few
      germinated and penetrated. Intracellular colonisation by B. bassiana was not
      observed, but hyphae were detected growing into the xylem vessels. The fungus was
      found to colonise 40.5 +/- 4.3% of seedlings (with two cotyledons and the two
      first real leaves) from seeds dressed with a fungal spore suspension. These
      results may have implications in the biological control of T. papaveris,
      including the possible systemic protection of the plant against this cynipid.

PMID- 16649083
TI  - Description of the life-cycle of the pearl millet rust fungus--Puccinia
      substriata var. penicillariae with a proposal of reducing var. indica to a
      synonym.
AB  - Pearl millet (Pennisetum glaucum) is a major staple food crop in the drier parts
      of the old world, like Africa and India. Recently, its cultivation became more
      widespread in no-tillage crop farming systems in central Brazil, but it is also
      being used for cultivation during the dry season in other areas in Brazil. An
      emerging problem for the wider adoption of this crop in Brazil is the damage
      caused by the rust Puccinia substriata. This fungal disease is among the worst
      limitations for this crop worldwide. The rust occurring in Brazil was initially
      identified as the P. substriata var. penicillariae, but little information on the
      taxonomy and life-cycle of this rust is available in Brazil. The life-cycle of
      this rust variety remains somewhat obscure and the connection between the telial
      stage on pearl millet and the aecial stage on Solanaceae has never been
      experimentally demonstrated. Natural infection and inoculations under controlled
      conditions allowed for a complete description of all stages of this rust and the
      elucidation of its life-cycle, confirming that Solanum aethiopicum and Solanum
      melongena are aecial hosts. This coincidence for the alternate host and the
      limited and ambiguous morphological basis for the distinction of the varieties
      penicillariae and indica support the view that they are synonyms. Var. indica
      should be regarded as a late synonym of var. penicillariae.

PMID- 16649084
TI  - First case of Microsporum ferrugineum from Iran.
AB  - This is a first case of Microsporum ferrugineum from Iranian patient. A 42 year
      old man was examined for tinea faciei infection. Direct KOH preparations from
      skin scraping revealed hyaline septate branching mycelium. Cultures of skin
      scrapings yielded M. ferrugineum after three weeks. Isolate was identified based
      on colony morphology on Sabouraud's dextrose agar medium (S), microscopic
      morphology of slide culture, and biochemical reactions.

PMID- 16649091
TI  - Mice chronically fed a westernized experimental diet as a model of obesity,
      metabolic syndrome and osteoporosis.
AB  - BACKGROUND: Most studies in animals use diets with several features (for example
      low-fat, rich in micronutriments), likely to be strongly protective against
      chronic diseases. AIM OF THE STUDY: The present study, performed in wild type
      outbred mice, was designed to evaluate the validity of a model of 'westernized'
      (W) diet reproducing, as closely as possible, the overall composition of an
      average human regime in western countries RESULTS: In contrast to the standard
      (S) diet, the W diet triggered a marked increase in adiposity with some
      characteristics of metabolic syndrome (hypercholesterolemia,
      hyperinsulinemia...). There was an heterogeneity in the propensity to become
      obese upon exposure to the W diet in female mice. Overweight mice also presented
      some disturbances of renal function, such as hyperalbuminuria and hypocitraturia.
      Mice adapted to the W diet showed a reduction of bone mineral density, especially
      the non-obese ones. CONCLUSION: These data suggest that a model of westernized
      diet could be appropriate for exploring the effects of mutations, drugs, or
      specific nutritional factors in animals and could be more relevant for human
      situations.

PMID- 16649092
TI  - Mutation of the highly conserved cysteine residue 131 of the SCA14 associated
      PRKCG gene in a family with slow progressive cerebellar ataxia.

PMID- 16649093
TI  - Impaired thermal perception in cluster headache.
AB  - Cluster headache is characterized by attacks of severe periorbital pain.
      Repetitive burst activity in afferent fibers may induce plastic alterations in
      somatosensory synaptic processing as a prerequisite for recurring and chronic
      pain. This psychophysical study addressed hypothesized dysfunctions in
      craniofacial somatosensory processing in cluster headache disease. Thermal and
      mechanical sensory functions in the periorbital region were assessed by
      quantitative sensory testing (QST) in 25 cluster headache patients and 60 healthy
      volunteers. Perception of warmth (p<0.01), cold (p<0.000001), and pressure pain
      (p<0.05) was reduced on the cluster side as compared with the contralateral
      asymptomatic side. In contrast to healthy volunteers, warm detection threshold
      (WDT) and thermal sensory limen (TSL) on one side did not positively correlate
      with the other side. WDT and TSL negatively correlated with the elapsed time
      since last attack. All patients showed QST abnormalities on the headache side in
      comparison to healthy controls. Loss of sensory functions strongly preponderated
      gain. Several lines of evidence indicate a pivotal role of the hypothalamus in
      cluster headache pathophysiology. The impairment of warm and cold perception in
      patients may be based upon a dysfunction of the hypothalamus which is strongly
      involved in thermosensory control.

PMID- 16649094
TI  - Levodopa availability improves with progression of Parkinson's disease.
AB  - BACKGROUND: Previous pharmacokinetic trials with standard levodopa formulations
      showed a different behaviour of levodopa degradation in plasma of patients with
      Parkinson's disease (PD) in various stages. OBJECTIVES: To investigate
      associations between levodopa plasma levels in relation to the scored intensity
      of PD. SUBJECTS AND METHODS: We administered water soluble 100 mg levodopa and 25
      mg benserazide to 50 PD patients, taken off medication for at least 12 hours, and
      assessed the levodopa plasma concentrations during an 180 minutes period under
      standardised conditions. RESULTS: The computed area under the curve (AUC) values
      of levodopa plasma levels were significant higher in advanced PD patients. PD
      rating scores significantly correlated to the AUC outcomes and the maximum
      levodopa plasma concentration. CONCLUSIONS: Levodopa availability improves with
      progression of PD. This may result from deteriorated peripheral activity of
      levodopa metabolising enzymes or an increasing enteric dysfunction with
      subsequent better duodenal levodopa absorption or both.

PMID- 16649095
TI  - Long-term improvement of paroxysmal dystonic choreathetosis with acetazolamide.

PMID- 16649096
TI  - Multiple sclerosis in Jordan: A clinical and epidemiological study.
AB  - OBJECTIVES: To characterize the clinical, demographic and epidemiological
      features of multiple sclerosis (MS) in Jordan. METHODS: Data for consecutive
      Jordanian patients, fulfilling the McDonald criteria for clinically definite and
      clinically probable MS, during the time period 2004-2005 were collected and
      analyzed in the three major referral centers for MS in Jordan. RESULTS: We
      identified a total of 224 patients (165 females, 87%; 59 males, 13%). The mean
      (+/-SD) age of onset was 29.3 (+/-9.6) years, and mean (+/-SD) duration of
      illness was 3.9 (+/-9.3) years. The prevalence of MS in the city of Amman was
      39/100,000. The prevalence of MS in Irbid, north Jordan, was 38/100,000. The most
      frequent presentation was weakness (30.8%), followed by optic neuritis (20.1%),
      sensory impairment (19.6%), and ataxia (14.3%). A relapsing remitting pattern was
      identified in 90.2% of patients, the rest being primary and secondary
      progressive, and one patient had a progressive relapsing course. Family history
      of MS was found in 9.4% of the cases. About 60% of the patients were using
      interferon beta. The degree of physical disability was determined using the
      Expanded Disability Status Scale (EDSS). Younger age of onset, shorter duration
      of illness, a relapsing remitting pattern, and use of interferon were identified
      as statistically significant predictors of less disability. CONCLUSION: Jordan is
      a medium-high risk country for MS, with prevalence higher than what has
      previously been reported, possibly representing an increase in incidence.
      Clinical and demographic characteristics are similar to most reports worldwide.

PMID- 16649097
TI  - Contrast sensitivity, first-order motion and Initial ocular following in
      demyelinating optic neuropathy.
AB  - The ocular following response (OFR) is a measure of motion vision elicited at
      ultra-short latencies by sudden movement of a large visual stimulus. We compared
      the OFR to vertical sinusoidal gratings (spatial frequency 0.153 cycles/ degrees
      or 0.458 cycles/ degrees) of each eye in a subject with evidence of left optic
      nerve demyelination due to multiple sclerosis (MS). The subject showed
      substantial differences in vision measured with stationary low-contrast Sloan
      letters (20/63 OD and 20/200 OS at 2.5% contrast) and the Lanthony Desaturated 15
      hue color test (Color Confusion Index 1.11 OD and 2.14 OS). Compared with
      controls, all of the subject's OFR to increasing contrast showed a higher
      threshold. The OFR of each of the subject's eyes were similar for the 0.153
      cycles/ degrees stimulus, and psychophysical measurements of his ability to
      detect these moving gratings were also similar for each eye. However, with the
      0.458 cycles/ degrees stimulus, the subject's OFR was asymmetric and the affected
      eye showed decreased responses (smaller slope constant as estimated by the Naka
      Rushton equation). These results suggest that, in this case, optic neuritis
      caused a selective deficit that affected parvocellular pathways mediating higher
      spatial frequencies, lower-contrast, and color vision, but spared the field
      holding mechanism underlying the OFR to lower spatial frequencies. The OFR may
      provide a useful method to study motion vision in individuals with disorders
      affecting anterior visual pathways.

PMID- 16649098
TI  - Cerebrospinal fluid ferritin in chronic hydrocephalus after aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVES: Subarachnoid hemorrhage (SAH) is a common cause of chronic
      hydrocephalus. Blood in the subarachnoid space is intracranially metabolized to
      bilirubin and iron, and free iron is thereafter detoxified by ferritin. However,
      no studies have reported the relationship between intracranial heme metabolism
      and chronic hydrocephalus after SAH. The goal of this prospective study was to
      clarify the relationship between intracranial heme metabolism and chronic
      hydrocephalus after SAH. METHODS: The authors measured the levels of bilirubin,
      iron and ferritin in the cerebrospinal fluid (CSF) of 70 consecutive patients
      with aneurysmal SAH of Fisher computed tomography Group III, and determined the
      relationship between these substances' levels and hydrocephalus requiring
      ventriculoperitoneal shunting. RESULTS: The CSF concentrations of ferritin and
      inflammatory cells were significantly higher in shunted patients (n = 27) than in
      non-shunted patients (n = 43) on Days 3 and 4 (p < 0.05 in ferritin and p < 0.01
      in inflammatory cells) and 11 to 14 (p < 0.005 in ferritin) post-SAH. These
      results were independent of other clinical factors. The occurrence of chronic
      hydrocephalus was not affected by the extent of the intracranial heme metabolism
      in terms of the bilirubin and iron levels. CONCLUSIONS: This is the first study
      to show that patients who subsequently had chronic hydrocephalus requiring CSF
      shunting were associated with higher CSF levels of ferritin in the acute stage of
      SAH. Higher CSF ferritin levels may not reflect the amount of blood in the
      subarachnoid space that was intracranially metabolized, but rather more intense
      subarachnoid inflammatory reactions which may cause chronic hydrocephalus after
      SAH.

PMID- 16649099
TI  - Antithrombotic agents' use in patients with atrial fibrillation and acute
      cerebral ischemia.
AB  - BACKGROUND: although trials suggest a benefit of aspirin, and not of
      anticoagulation (AC), in the acute stage of cerebral ischemia associated with
      atrial fibrillation (AF), many neurologists still use heparin. OBJECTIVE: to
      evaluate how antithrombotic agents were used at the acute stage of cerebral
      ischemia in AF patients after the publication of trials and guidelines. METHODS:
      we reviewed the charts of all patients with AF who were admitted between 1996 and
      2002 as primary care patients, within 48 hours after onset of an ischemic stroke
      (IS) or transient ischemic attacks (TIAs). We recorded the first antithrombotic
      treatment prescribed at admission. RESULTS: in 763 consecutive patients (42% men;
      median age 79 years), the use of AC on admission decreased over time from 70% to
      22% (p<0.001), while antiplatelet agents increased from 27% to 78% (p<0.001).
      Patients who received AC were more likely to be younger, to have a Barthel index
      >60, no hemorrhagic changes, and to have been admitted in 1996 or 1997. Results
      were similar between patients with IS and TIAs and in patients who were not under
      AC before. In patients who were under oral AC before, AC use at admission did not
      decline over time (p=0.366). CONCLUSION: there was a clear decrease in AC use
      during the study period, except in patients who were already under AC before, and
      in TIA patients.

PMID- 16649100
TI  - Multicystic tumor in the fourth ventricle: consider neurocysticercosis.

PMID- 16649101
TI  - [Abstracts of the 72nd Annual Meeting of the German Cardiac Society].

PMID- 16649102
TI  - Expression profiles of 10,422 genes at early stage of low nitrogen stress in rice
      assayed using a cDNA microarray.
AB  - Development of crop varieties with high nitrogen use efficiency (NUE) is
      imperative for sustainable agriculture. Understanding how plant genes respond to
      low N stress is essential for formulating approaches to manipulating genes for
      improving NUE. In this study we analyzed the expression profiles of an indica
      rice cultivar Minghui 63 at seedling stage at 20 min, 1 and 2 h after low N
      stress with the normal N as the control, using a microarray of 11,494 rice ESTs
      representing 10,422 unique genes. While no significant difference was detected in
      the leaf tissue, a total of 471 ESTs were detected as responsive to low N stress
      in the root tissue with 115 ESTs showing up-regulation and 358 ESTs showing down
      regulation. The analysis of expression profiles after low N stress identified
      following patterns: (1) the genes involved in photosynthesis and energy
      metabolism were down-regulated rapidly; (2) many of the genes involved in early
      responses to biotic and abiotic stresses were up-regulated while many other
      stress responsive genes were down-regulated; (3) regulatory genes including
      transcription factors and ones involved in signal transduction were both up- and
      down-regulated; and (4) the genes known to be involved in N uptake and
      assimilation showed little response to the low N stress. The challenges for
      future studies are to characterize the functional roles of the low N stress
      responsive genes in N metabolisms, including the large number of genes presently
      with unknown functions.

PMID- 16649103
TI  - Asparagales telomerases which synthesize the human type of telomeres.
AB  - The order of monocotyledonous plants Asparagales is attractive for studies of
      telomere evolution as it includes three phylogenetically distinct groups with
      telomeres composed of TTTAGGG (Arabidopsis-type), TTAGGG (human-type) and unknown
      alternative sequences, respectively. To analyze the molecular causes of these
      switches in telomere sequence (synthesis), genes coding for the catalytic
      telomerase subunit (TERT) of representative species in the first two groups have
      been cloned. Multiple alignments of the sequences, together with other TERT
      sequences in databases, suggested candidate amino acid substitutions grouped in
      the Asparagales TERT synthesizing the human-type repeat that could have
      contributed to the changed telomere sequence. Among these, mutations in the C
      motif are of special interest due to its functional importance in TERT.
      Furthermore, two different modes of initial elongation of the substrate primer
      were observed in Asparagales telomerases producing human-like repeats, which
      could be attributed to interactions between the telomerase RNA subunit (TR) and
      the substrate.

PMID- 16649104
TI  - Post-transcriptional gene silencing of GBSSI in potato: effects of size and
      sequence of the inverted repeats.
AB  - In the past, silencing of granule-bound starch synthase (GBSSI) in potato was
      achieved by antisense technology, where it was observed that inclusion of the 3'
      end of the GBSSI coding region increased silencing efficiency. Since higher
      silencing efficiencies were desired, GBSSI inverted repeat constructs were
      designed and tested in potato. First, large inverted repeats comprising the 5'
      and the 3' half of the GBSSI cDNA were tested. The 5' IR construct gave a
      significantly higher silencing efficiency than the 3' IR construct. Since it was
      not known whether the observed difference was due to the sequence or the
      orientation of the inverted repeat, the GBSSI cDNA was divided into three
      regions, after which each region was tested in small inverted repeats in two
      orientations. To this end large numbers of independent transformants were
      produced for each construct. The results suggested that there was no effect of
      inverted repeat orientation on silencing efficiency. The percentage of
      transformants showing strong inhibition varied from 48% for a 3'-derived
      construct to 87% for a 5' as well as a middle region-derived construct. Similar
      to the large inverted repeats, the 3' sequences induced the least efficient
      silencing implying that the observed differences in silencing efficiency are
      caused by sequence differences. The small inverted repeat constructs with a
      repeat size of 500-600 bp and a spacer of about 150 bp were more efficient
      silencing inducers than the large inverted repeat constructs where the size of
      the repeat was 1.1 or 1.3 kb whilst the size of spacer was 1.3 or 1.1 kb. The
      results presented here show that size and sequence of the inverted repeat
      influenced silencing efficiency.

PMID- 16649105
TI  - Identification of a glycosylphosphatidylinositol-anchored plasma membrane protein
      interacting with the C-terminus of auxin-binding protein 1: a photoaffinity
      crosslinking study.
AB  - Synthetic peptides corresponding to the C-terminus of auxin-binding protein 1
      (ABP1) have been shown to function as auxin agonists. To define a C-terminal
      receptor, photoaffinity crosslinking experiments were performed using an azido
      derivative of a C-terminal peptide and plasma membranes from maize (Zea mays L.).
      The crosslinking reaction was monitored by immunoblotting using anti-ABP1
      antibodies. The crosslinked proteins were isolated by 2D gel electrophoresis and
      identified by mass spectrometric analysis. Further, the noncrosslinked forms of
      these proteins were also identified. Two proteins with apparent molecular masses
      of 73 kDa (termed C-terminal peptide-binding protein 1, CBP1) and 35 kDa (CBP2)
      were specifically linked with the C-terminal peptide. CBP2 is a cytoplasmic
      protein that consists of two conserved domains that are characteristic of a ricin
      type lectin domain. CBP2 remained in the detergent-insoluble particles and was
      released from the particles by the addition of monosaccharides such as methyl
      beta-D-galactopyranoside. CBP1 was released from the membranes by treatment with
      phosphatidylinositol-specific phospholipase C, indicating that CBP1 is a
      glycosylphosphatidylinositol (GPI)-anchored plasma membrane protein. CBP1 was
      found to be a copper-binding protein, and is highly homologous to Arabidopsis
      thaliana SKU5 that contributes to directional root growth processes. Further, it
      is similar to A. thaliana SKS6 that contributes to cotyledon vascular patterning
      and to Nicotiana tabacum NTP303 that contributes to pollen tube growth. The
      present results indicate that ABP1 may contribute to directional cell growth
      processes via the GPI-anchored plasma membrane protein SKU5 and its family
      members.

PMID- 16649106
TI  - "HAIRY CANOLA"--Arabidopsis GL3 induces a dense covering of trichomes on Brassica
      napus seedlings.
AB  - Transformation with the Arabidopsis bHLH gene 35S:GLABRA3 (GL3) produced novel B.
      napus plants with an extremely dense coverage of trichomes on seedling tissues
      (stems and young leaves). In contrast, trichomes were strongly induced in
      seedling stems and moderately induced in leaves of a hairy, purple phenotype
      transformed with a 2.2 kb allele of the maize anthocyanin regulator LEAF COLOUR
      (Lc), but only weakly induced by BOOSTER (B-Peru), the maize Lc 2.4 kb allele, or
      the Arabidopsis trichome MYB gene GLABRA1 (GL1). B. napus plants containing only
      the GL3 transgene had a greater proportion of trichomes on the adaxial leaf
      surface, whereas all other plant types had a greater proportion on the abaxial
      surface. Progeny of crosses between GL3+ and GL1+ plants resulted in trichome
      densities intermediate between a single-insertion GL3+ plant and a double
      insertion GL3+ plant. None of the transformations stimulated trichomes on
      Brassica cotyledons or on non-seedling tissues. A small portion of bHLH gene
      induced trichomes had a swollen terminal structure. The results suggest that
      trichome development in B. napus may be regulated differently from Arabidopsis.
      They also imply that insertion of GL3 into Brassica species under a tissue
      specific promoter has strong potential for developing insect-resistant crop
      plants.

PMID- 16649107
TI  - The A and B loci in tobacco regulate a network of stress response genes, few of
      which are associated with nicotine biosynthesis.
AB  - Nicotine biosynthesis in Nicotiana tabacum is under genetic control by the A and
      B loci. Plants containing semi-dominant mutations at both the A and B loci (i.e.
      aabb genotype) have lower nicotine levels, reduced nicotine biosynthetic enzyme
      activities, and reduced mRNA levels of the corresponding biosynthetic genes. The
      A and B loci therefore appear to be coordinate regulators of several nicotine
      biosynthetic genes and define a group of co-regulated genes called the A-B
      regulon. To investigate the composition of genes in the A-B regulon, a
      fluorescent differential display (FDD) screen was used to randomly sample the
      transcriptomes of wild type and mutant aabb roots. This resulted in the isolation
      of 64 FDD clones, representing 49 unique genes or gene families. Four genes
      associated with nicotine biosynthesis were identified, whereas most of the other
      FDD clones were homologous with an assortment of stress response genes. Thirty
      three genes or gene families showed reproducible aabb genotype effects,
      representing seven distinct mRNA expression patterns in response media treatments
      that increase the mRNA levels of known alkaloid biosynthetic genes. Thus, the A
      and B loci regulate the mRNA levels of some target genes differently than others.
      Eleven genes or gene families showed only treatment-specific effects,
      representing four mRNA accumulation patterns. These results indicate the A-B
      regulon is complex network of differentially expressed stress response genes,
      only a small subset of which are involved in nicotine biosynthesis.

PMID- 16649108
TI  - Expression of a Brassica isopropylmalate synthase gene in Arabidopsis perturbs
      both glucosinolate and amino acid metabolism.
AB  - Isopropylmalate synthase (IPMS) is a key enzyme in the biosynthesis of the
      essential amino acid leucine, and thus primary metabolism. In Arabidopsis, the
      functionally similar enzyme, methythiolalkylmalate synthase (MAM), is an
      important enzyme in the elongation of methionine prior to glucosinolate (GSL)
      biosynthesis, as part of secondary metabolism. We describe the cloning of an IPMS
      gene from Brassica, BatIMS, and its functional characterisation by heterologous
      expression in E. coli and Arabidopsis. Over expression of BatIMS in Arabidopsis
      resulted in plants with an aberrant phenotype, reminiscent of mutants in GSL
      biosynthesis. Metabolite analyses showed that these plants had both perturbed
      amino acid metabolism and enhanced levels of GSLs. Microarray profiling showed
      that BatIMS over expression caused up regulation of the genes for methionine
      derived GSL biosynthesis, and down regulation of genes involved in leucine
      catabolism, in addition to perturbed expression of genes involved in auxin and
      ethylene metabolism. The results illustrate the cross talk that can occur between
      primary and secondary metabolism within transgenic plants.

PMID- 16649109
TI  - The highly charged region of plant beta-type phosphatidylinositol 4-kinase is
      involved in membrane targeting and phospholipid binding.
AB  - In Arabidopsis thaliana and Oryza sativa, two types of PI 4-kinase (PI4Ks) have
      been isolated and functionally characterized. The alpha-type PI4Ks (approximately
      220 kDa) contain a PH domain, which is lacking in beta-type PI4Ks (approximately
      120 kDa). Beta-type PI4Ks, exemplified by Arabidopsis AtPI4Kbeta and rice
      OsPI4K2, contain a highly charged repetitive segment designated PPC (Plant PI4K
      Charged) region, which is an unique domain only found in plant beta-type PI4Ks at
      present. The PPC region has a length of approximately 300 amino acids and
      harboring 11 (AtPI4Kbeta) and 14 (OsPI4K2) repeats, respectively, of a 20-aa
      motif. Studies employing a modified yeast-based "Sequence of Membrane-Targeting
      Detection" system demonstrate that the PPC(OsPI4K2) region, as well as the former
      8 and latter 6 repetitive motifs within the PPC region, are able to target fusion
      proteins to the plasma membrane. Further detection on the transiently expressed
      GFP fusion proteins in onion epidermal cells showed that the PPC(OsPI4K2) region
      alone, as well as the region containing repetitive motifs 1-8, was able to direct
      GFP to the plasma membrane, while the regions containing less repetitive motifs,
      i.e. 6, 4, 2 or single motif(s) led to predominantly intracellular localization.
      Agrobacterium-mediated transient expression of PPC-GFP fusion protein further
      confirms the membrane-targeting capacities of PPC region. In addition, the
      predominant plasma membrane localization of AtPI4Kbeta was mediated by the PPC
      region. Recombinant PPC peptide, expressed in E. coli, strongly binds
      phosphatidic acid, PI and PI4P, but not phosphatidylcholine, PI5P, or PI(4,5)P2
      in vitro, providing insights into potential mechanisms for regulating sub
      cellular localization and lipid binding for the plant beta-type PI4Ks.

PMID- 16649110
TI  - Rejuvenation by shoot apex culture recapitulates the developmental increase of
      methylation at the maize gene Pl-Blotched.
AB  - Cytosine methylation provides an attractive epigenetic modification for the
      global maintenance of phases in plant development; however, there are few known
      examples of specific genes whose methylation status changes in a developmentally
      regulated manner. Pl-Blotched, an allele of purple plant1 (pl1), which encodes a
      myb-like transcription factor that regulates anthocyanin production in maize, is
      one such gene: certain cytosines at the 3' end of this allele are hypomethylated
      in seedlings, become hypermethylated in organs formed in the adult phase, and are
      hypomethylated again in the next generation. We tested whether this developmental
      pattern of low juvenile cytosine methylation followed by higher methylation in
      adult tissues could also be observed in plants "rejuvenated" via shoot apex
      culture. We found that cytosine methylation patterns at Pl-Blotched were indeed
      recapitulated in culture-rejuvenated plants, showing hypomethylation in leaves
      with juvenile patterns of differentiation (even though they were made by an old
      meristem) followed by hypermethylation in later-formed leaves. Our results show
      that methylation status at that locus is determined by the developmental phase of
      the shoot, rather than by the age of the meristem forming it. These results
      support the hypothesis that DNA methylation is employed by the plant to maintain
      an epigenetic state.

PMID- 16649111
TI  - The heat stress transcription factor HsfA2 serves as a regulatory amplifier of a
      subset of genes in the heat stress response in Arabidopsis.
AB  - Within the Arabidopsis family of 21 heat stress transcription factors (Hsfs)
      HsfA2 is the strongest expressed member under heat stress (hs) conditions.
      Irrespective of the tissue, HsfA2 accumulates under heat stress similarly to
      other heat stress proteins (Hsps). A SALK T-DNA insertion line with a complete
      HsfA2-knockout was analyzed with respect to the changes in the transcriptome
      under heat stress conditions. Ascorbate peroxidase 2 (APX2) was identified as the
      most affected transcript in addition to several sHsps, individual members of the
      Hsp70 and Hsp100 family, as well as many transcripts of genes with yet unknown
      functions. For functional validation, the transcription activation potential of
      HsfA2 on GUS reporter constructs containing 1 kb upstream promoter sequences of
      selected target genes were analyzed using transient reporter assays in mesophyll
      protoplasts. By deletion analysis the promoter region of the strongest affected
      target gene APX2 was functionally mapped in detail to verify potential HsfA2
      binding sites. By electrophoretic mobility shift assays we identified TATA-Box
      proximal clusters of heat stress elements (HSE) in the promoters of selected
      target genes as potential HsfA2 binding sites. The results presented here
      demonstrate that the expression of HsfA2 in Arabidopsis is strictly heat stress
      dependent and this transcription factor represents a regulator of a subset of
      stress response genes in Arabidopsis.

PMID- 16649112
TI  - Conversion of MapMan to allow the analysis of transcript data from Solanaceous
      species: effects of genetic and environmental alterations in energy metabolism in
      the leaf.
AB  - The tomato microarray TOM1 offers the possibility to monitor the levels of
      several thousand transcripts in parallel. The microelements represented on this
      tomato microarray have been putatively assigned to unigenes, and organised in
      functional classes using the MapMan ontology (Thimm et al., 2004. Plant J. 37:
      914-939). This ontology was initially developed for use with the Arabidopsis ATH1
      array, has a low level of redundancy, and can be combined with the MapMan
      software to provide a biologically structured overview of changes of transcripts,
      metabolites and enzyme activities. Use of this application is illustrated using
      three case studies with published or novel TOM1 array data sets for Solanaceous
      species. Comparison of previously reported data on transcript levels in potato
      leaves in the middle of the day and the middle of the night identified
      coordinated changes in the levels of transcripts of genes involved in various
      metabolic pathways and cellular events. Comparison with diurnal changes of gene
      expression in Arabidopsis revealed common features, illustrating how MapMan can
      be used to compare responses in different organisms. Comparison of transcript
      levels in new experiments performed on the leaves of the cultivated tomato S.
      lycopersicum and the wild relative S. pennellii revealed a general decrease of
      levels of transcripts of genes involved in terpene and, phenylpropanoid
      metabolism as well as chorismate biosynthesis in the crop compared to the wild
      relative. This matches the recently reported decrease of the levels of secondary
      metabolites in the latter. In the third case study, new expression array data for
      two genotypes deficient in TCA cycle enzymes is analysed to show that these
      genotypes have elevated levels of transcripts associated with photosynthesis.
      This in part explains the previously documented enhanced rates of photosynthesis
      in these genotypes. Since the Solanaceous MapMan is intended to be a community
      resource it will be regularly updated on improvements in tomato gene annotation
      and transcript profiling resources.

PMID- 16649113
TI  - Need for guidelines for screening in anal cancer: a lesson from cervical cancer.

PMID- 16649114
TI  - Focus Group on Laparoscopic Colectomy Education as endorsed by The American
      Society of Colon and Rectal Surgeons (ASCRS) and The Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES).

PMID- 16649117
TI  - Preoperative anal manometry predicts continence after perineal proctectomy for
      rectal prolapse.
AB  - PURPOSE: This study examines whether preoperative anal manometry and pudendal
      nerve terminal motor latency predict functional outcome after perineal
      proctectomy for rectal prolapse. METHODS: All adult patients treated by perineal
      proctectomy for rectal prolapse from 1995 to 2004 were identified (N = 106).
      Forty-five patients underwent anal manometry and pudendal nerve terminal motor
      latency testing before proctectomy and they form the basis for this study.
      RESULTS: Perineal proctectomy with levatoroplasty (anterior 88.9 percent;
      posterior 75.6 percent) was performed in all patients, with a mean resection
      length of 10.4 cm. Four patients (8.9 percent) developed recurrent prolapse
      during a 44-month mean follow-up. Preoperative resting and maximal squeeze
      pressures were 34.2 +/- 18.3 and 60.4 +/- 30.5 mmHg, respectively. Pudendal nerve
      terminal motor latency testing was prolonged or undetectable in 55.6 percent of
      patients. Grade 2 or 3 fecal incontinence was reported by 77.8 percent of
      patients before surgery, and one-third had obstructed defecation. The overall
      prevalence of incontinence (77.8 vs. 35.6 percent, P < 0.0001) and constipation
      (33.3 vs. 6.7 percent, P = 0.003) decreased significantly after proctectomy.
      Patients with preoperative squeeze pressures >60 mmHg (n = 19) had improved
      postoperative fecal continence relative to those with lower pressures
      (incontinence rate, 10 vs. 54 percent; P = 0.004), despite having similar degrees
      of preoperative incontinence. Abnormalities of pudendal nerve function and mean
      resting pressures were not predictive of postoperative incontinence. CONCLUSIONS:
      Perineal proctectomy provides relief from rectal prolapse, with good intermediate
      term results. Preoperative anal manometry can predict fecal continence rates
      after proctectomy, because patients with maximal squeeze pressures >60 mmHg have
      significantly improved outcomes.

PMID- 16649125
TI  - Osteoma in the upper cervical spine with spinal cord compression.
AB  - Osteoma is a common benign tumor. It occurs dominantly at the skull bone. Outside
      skull osteoma is rare, and primary intra-canal osteoma is extremely rare. To the
      author's knowledge, only 14 cases of osteomas of the spine had been reported, in
      which only seven cases were in English literature. The authors reported two rare
      cases of intra-canal osteoma of the upper cervical spine with cord compression.
      Included are pertinent history, physical examination, rontgenographic evaluation
      before and after operation, surgical interventions, pathological study, and
      outcome. The available literature is also reviewed. On systemic examination and
      rontgenographic study, these two cases were found to have bone tumor in the upper
      cervical canal. Surgical interventions were performed, one with an en bloc
      excision, the other with a subtotal excision. The pathological study demonstrated
      a diagnosis of osteoma. After a follow-up with 20 and 15 months, the clinical
      symptoms of both cases significantly improved.

PMID- 16649126
TI  - Higher mortality and different pattern of causes of death among foreign-born
      compared to native Swedes 1970-1999.
AB  - In a previous Swedish longitudinal study of mortality among 723,948 foreign born
      and native-born Swedes, 1970-1999, increased mortality was found among foreign
      born persons. This study describes and analyses the differences in mortality
      between 361,974 foreign-born persons and 361,974 native Swedes during the period
      1970-1999, based on data from Statistics Sweden and the National Board of Health
      and Welfare. The mortality pattern showed dissimilarities; with a significantly
      higher number of deaths among foreign-born persons in six diagnose groups and a
      significantly lower mean age at time of death. A high number of deaths were found
      for migrants from Denmark in Neoplasm, for migrants from Finland and Poland in
      Diseases of the circulatory system and for migrants from Yugoslavia in Symptoms,
      signs and ill-defined conditions. There is a tendency to a more similar pattern
      between foreign- and Swedish-born persons over time. Migration may be a risk
      factor for health, and therefore seems to be an important factor to consider when
      studying morbidity and health and when planning preventive work.

PMID- 16649127
TI  - Cultural dissimilarities in general practice: development and validation of a
      patient's cultural background scale.
AB  - Due to increased migration physicians encounter more communication difficulties
      due to poor language proficiency and different culturally defined views about
      illness. This study aimed to develop and validate a 'patient's cultural
      background scale' in order to classify patients based on culturally conditioned
      norms instead of on ethnicity. A total of 986 patients from 38 multi-ethnic
      general practices were included. From a list of 36 questions, non-contributing
      and non-consistent questions were deleted and from the remaining questions the
      scale was constructed by principal component analysis. Comparing the scale with
      two other methods of construction assessed internal validity. Comparing the found
      dimensions with known dimensions from literature assessed the construct validity.
      Criterion validity was determined by comparing the patient's score with criteria
      assumed or known to have relationship with cultural background. Criterion
      validity was reasonably good but poor for income. A valid patient's cultural
      background scale was developed, for use in large-scale quantitative studies.

PMID- 16649128
TI  - 'Nobody can help me...i am living through it alone': experiences of caring for
      people diagnosed with mental illness in ethno-cultural and linguistic minority
      communities.
AB  - Caregivers of people diagnosed with mental illness in ethno-cultural and
      linguistic minority communities (ECLMCs) face considerable demands and
      difficulties in their day-to-day caring role. Data from interviews with 20
      caregivers from Polish, Croatian, Bosnian, and Chinese communities, undertaken in
      Perth, Western Australia, explore the roles caregivers play in the lives of their
      relatives and illustrate their use and non-use of support services. A diverse
      array of challenges confronts caregivers across the different ECLMCs. Although
      not an unequivocally negative experience, caring for a relative diagnosed with
      mental illness was found to frequently disrupt family relationships and to lead
      to physical and mental exhaustion as well as social isolation. The stigma
      associated with mental illness in ECLMCs is a significant factor dissuading
      people from seeking assistance from external agencies. Many mainstream services
      are seen as inappropriate, which appears to be a factor in their under
      utilization. If mental health policies and community services are to seriously
      address the issue of appropriate support for caregivers from ECLMCs, it is
      important that they are aware of the nature of the considerable demands placed on
      such caregivers as they endeavor to support their dependent relatives.

PMID- 16649129
TI  - Health-care outcomes in ethnoculturally discordant medical encounters: the role
      of physician transnational competence in consultations with asylum seekers.
AB  - In this mobility-upheaval era, many health outcomes are shaped by transnational
      interactions among care-providers and recipients who meet in settings where
      nationality/ethnic match is a diminishing option. This exploratory study compares
      health-care outcomes in ethnoculturally discordant medical encounters according
      to patient national/ethnic identity, frequency (intensity) of medical
      consultation, and physician transnational competence (TC). Analysis is based on
      interviews with 35 political-asylum seekers and their ethnoculturally discordant
      clinicians at five reception centres in Finland. The three medical-encounter
      outcomes considered are patient-reported adherence with medication instructions,
      satisfaction, and confidence in the principal attending physician's
      recommendations. The intersubjectively assessed overall transnational competence
      of the attending physician provided the strongest association with all three
      outcome measures. The results of exploratory study suggest that preparing medical
      students with skills that can be applied effectively in variable transnational
      encounter contexts would help close disparities in certain health-care outcomes.

PMID- 16649130
TI  - Insurance status and health service utilization among newly-arrived older
      immigrants.
AB  - Following the 1996 welfare reform, newly arrived older immigrants with less than
      5 years of residence (NOIs) have been barred from Medicaid benefits. Neither are
      they eligible for Medicare due to lack of work history. This study examines the
      relationship between immigrant status (NOIs or not), health insurance, and health
      service use among older immigrants; whether insurance mediates the relationship
      between immigrant status and health service use. The 2000 National Health
      Interview Survey was analyzed. The sample includes respondents aged 65 or older
      who are foreign-born (N=1, 178). The adapted Andersen model was used. A series of
      logistic regressions show insurance is a complete mediator between immigrant
      status and health service use among older immigrants. Immigrant status was
      significantly related to the mediator, health insurance; older immigrants with
      longer than 5 years of residence were 31 times more likely than NOIs to have
      health insurance in terms of odds. Also, different from health service use among
      U.S.-born older adults, older immigrants' service use is significantly related to
      their insurance status. There was no direct relationship between immigrant status
      and health service use.

PMID- 16649131
TI  - Characteristics and utilization of primary care services in a torture
      rehabilitation center.
AB  - We conducted a retrospective chart review to look into the utilization of
      healthcare services of refugees. Between December 1998 and June 2001, 146
      refugees received care at the Boston Center for Refugee Health and Human Rights.
      The mean age was 39+/- 1 years; 57% were males, and 84% were survivors of
      torture. A significant number of patients were diagnosed with major depression
      (70%), post-traumatic stress disorder (58%), past hepatitis A infection (77%),
      and tuberculosis classes 2 and 3 (42%). Patients had on average 2.3 +/- 0.1
      initial health assessments visits and 3.6 +/- 0.3 primary care follow-up visits
      during a mean follow-up period of 12.8 +/- 0.8 months. Subjects with two or fewer
      initial health assessment visits were less likely to be undergoing psychological
      counseling (OR: 0.22; 95% CI:0.08-0.58), less likely to be seeking asylum (OR:
      0.16; 95% CI: 0.06-0.43), and more likely to be self-referred (OR: 9.6; 95%
      CI:2.4-39.6). Four or fewer primary care follow-up visits were more likely in
      subjects who had no health insurance (OR: 7.2; 95% CI:2.0-25.5) and less likely
      in those referred for psychological counseling (OR: 0.017; 95% CI:0.05-0.54).
      Patients had a higher prevalence of mental health conditions than that reported
      in other studies and often declined diagnostic and therapeutic interventions.

PMID- 16649132
TI  - Housing characteristics of farmworker families in North Carolina.
AB  - Adequate housing is a basic human right and an important determinant of
      environmental health. Little research has documented the housing quality of
      immigrant Latino farmworker families. This analysis uses data from four surveys
      of North Carolina farmworker communities conducted in 2001 and 2003 to document
      aspects of housing quality that could affect farmworker family health. Three
      housing domains are considered: dwelling characteristics, household
      characteristics, and household behaviors. Most farmworker families live in mobile
      homes, and few own their dwellings. Many are located near agricultural fields.
      Most houses are small, but household size is large, containing adults, in
      addition to the nuclear family. Crowding is common among farmworker families.
      Many farmworker households lack basic facilities, such as washing machines.
      Farmworkers attempt to reduce exposure by frequently cleaning their dwellings.
      These findings suggest that the health of farmworker families is at risk due to
      inadequate housing. Further research on housing-related health effects among
      farmworker families is needed.

PMID- 16649133
TI  - Estimating the incidence of heat-related deaths among immigrants in Pima County,
      Arizona.
AB  - Widespread media reports have described an increase in heat-related deaths among
      illegal immigrant border crossers in Southern Arizona in recent years. We
      conducted a retrospective case series review of heat-related deaths reported by a
      large border county medical examiner office in an attempt to estimate the
      occurrence and distribution of these deaths for the years 1998-2003. United
      States Border Patrol apprehension data were also collected and used in the
      analysis to estimate the size of the population of border crossers. An increase
      in the total heat-related deaths has occurred since 1999 in Pima County Arizona
      and has continued to date. Precise estimates of rates are not possible but appear
      to have increased as well. Implications for understanding the complexity of
      researching this public health issue including the definition of cases and
      population at risk are discussed.

PMID- 16649135
TI  - Use of airborne gamma-ray spectrometry for environmental assessment of the
      rehabilitated nabarlek uranium mine, Australia.
AB  - This article describes an airborne gamma survey of a 7 x 5 km region around the
      rehabilitated Nabarlek uranium mine in northern Australia. An unusually tight
      line spacing (100 m) and low aircraft height (50 m) were used, enabling the
      survey to distinguish man-made structures such as ponds and accommodation areas,
      as well as creek lines. Positive correlations between airborne data and ground
      based readings enabled an estimation of the average absorbed dose rate arising
      from terrestrial gamma radiation over large areas of the site to be derived. For
      the fenced minesite area this estimate was 0.31 micro Gy hr(- 1). The airborne
      survey data were found to be invaluable in helping to plan further ground-level
      investigations and showed promise as an assessment tool for rehabilitated
      minesites.

PMID- 16649136
TI  - Screening-level risk assessment of Di(2-ethylhexyl)phthalate for aquatic
      organisms using monitoring data in Japan.
AB  - Screening-level ecological risk assessments of di(2-ethylhexyl)phthalate (DEHP)
      for aquatic organisms in Japan were conducted using estimated statistical values
      based on surface water and sediment monitoring data and effect threshold values
      based on a large aquatic toxicity database. An alternative method is proposed to
      handle monitoring data that contain nondetects including multiple detection
      limits and to determine the statistical values of DEHP concentrations in Japanese
      surface waters. The No-Observed-Effect-Concentration (NOEC(water)) of DEHP for
      aquatic life of 77 micro g/L was determined giving equal importance to both
      physical effects probably caused by undissolved DEHP and to the intrinsic
      toxicity potentially caused by DEHP. The NOEC(sediment) of 615,000 micro g/kg was
      determined by the Equilibrium Partitioning (EqP) theory, conservatively assuming
      a threshold effect level in the water column as the water solubility of 3 micro
      g/L. The potential risks of DEHP in Japanese water environments were
      characterized simply by comparing the margin of exposure (MOE) with a specified
      uncertainty multiplier (UM). The MOE is expressed as the ratio of NOEC(water) or
      NOEC(sediment) to the expected environmental concentrations such as the 95th
      percentiles of the estimated DEHP concentration distributions for surface water
      or sediment. The results of risk characterization show that all MOE values
      calculated using the statistical values of DEHP concentrations in Japanese
      surface waters and sediments are above 10, indicating minimal risk. Although the
      DEHP concentrations of some surface water samples showed MOE values of less than
      10, considering environmental chemistry such as bioavailable fractions and the
      form of existence of DEHP in a water environment, we conclude that the current
      levels of DEHP are of little concern to aquatic life in the majority of Japanese
      surface waters and sediments.

PMID- 16649137
TI  - Variation of metals in bed sediments of Qaraaoun Reservoir, Lebanon.
AB  - The Qaraaoun Reservoir (impoundment of the River Litani) is the only artificial
      surface water body in the country, Lebanon. Earlier study on the water quality of
      the Qaraaoun Reservoir identified three water quality zoning with a central
      distinct zone suitable for multipurpose water usage. The objective of this study
      was to extend the earlier work by considering the total metal content of
      reservoir bed sediments and hence to evaluate factors that control metal
      deposition or capture. Water samples were collected from 15 sampling sites and
      sediment samples were simultaneously collected from 9 sites. Water parameters
      analyzed were pH, Eh, DO and temperature. Sediment samples were dried and sieved
      and sediment < 75 microm was retained for analysis. Sediments were subjected to a
      stepwise heating process with aqua regia to extract the metals, and their content
      in sediments determined by ICP-MS. The sediment data revealed higher metal
      contents where the river entered the reservoir which matched higher
      concentrations of water parameters at the influx site. Regression analysis of
      total metals in sediments with distance from the river Litani influx point to the
      dam revealed a log trend for Fe, Cr and Ni, whereas, the concentrations of Cu,
      Zn, Cd, Pb were better described by a polynomial regression. Three sediment zones
      were identified: entrance, oxidation (central) and reducing (near dam) zones.
      Sediment contents of Zn, Cu and Pb correlated with organic content, whereas
      sediment Cr and Ni were associated with iron. It was concluded that sediments act
      as a sink for metals and the deposition of metals is primarily related to
      sediment organic content and the level of dissolved oxygen in water.

PMID- 16649138
TI  - Assessment and treatment of hydrocarbon inundated soils using inorganic nutrient
      (N-P-K) supplements: II. A case study of eneka oil spillage in Niger Delta,
      Nigeria.
AB  - Polluted soils from Eneka oil field in the Niger delta region of Nigeria were
      collected two months after recorded incidence of oil spillage as part of a two
      site reclamation programme. The soils were taken on the second day of
      reconnaissance from three replicate quadrats, at surface (0-15 cm) and subsurface
      (15-30 cm) depths, using the grid sampling technique. Total extractable
      hydrocarbon content (THC) of the polluted soils ranged from 1.006 x 10(3)-5.540 x
      10(4) mg/kg at surface and subsurface depths (no overlap in Standard Errors at
      95% Confidence Level). Greenhouse trials for possible reclamation were later
      carried out using (NH(4))(2)SO(4), KH(2)PO(4) and KCl (N-P-K) fertilizer as
      nutrient supplements. Nitrogen as NO(3)-N and potassium were optimally enhanced
      at 2% (w/w) and 3% (w/w) of the N-P-K supplementation respectively. Phosphorus,
      which was inherently more enhanced in the soils than the other nutrients,
      maintained same level impact after 20 g treatment with the N-P-K fertilizer.
      Total organic carbon (%TOC), total organic matter (%TOM), pH and % moisture
      content all provided evidence of enhanced mineralization in the fertilizer
      treated soils. If reclamation of the crude oil inundated soils is construed as
      the return to normal levels of metabolic activities of the soils, then the
      application of the inorganic fertilizers at such prescribed levels would duly
      accelerate the remediation process. This would be, however, limited to levels of
      pollution empirically defined by such THC values obtained in this study. The data
      on the molecular compositional changes of the total petroleum hydrocarbon content
      (TPH) of the spilled-oil showed the depletion of the fingerprints of the n
      paraffins, nC(8)-nC(10), and complete disappearance of C(12)-C(17) as well as the
      acyclic isoprenoid, pristane, all of which provided substantial evidence of
      degradation.

PMID- 16649140
TI  - Regulation of fat metabolism in the liver: link to non-alcoholic hepatic
      steatosis and impact of physical exercise.
AB  - Hepatic steatosis may develop as a consequence of several dysfunctions. An
      increased circulating non-esterified fatty acid (NEFA) pool seems to be a major
      determinant in the pathogenesis of non-alcoholic fatty liver disease. Increased
      activation of the transcription factor sterol-regulatory-element-binding protein
      1c, which promotes fatty acid synthesis, also contributes to hepatic fat
      accumulation. Increased hepatic fat oxidation with hepatic steatosis may be
      triggered by increased hepatic fat concentrations through the action of hepatic
      peroxisomes mediated by peroxisome proliferator-activated receptor alpha.
      Finally, inhibition in very low density lipoprotein secretion may also result in
      hepatic steatosis. This appears to be mainly controlled by the esterification of
      NEFAs into triacylglycerols by diacyglycerol acyltransferase-1 and -2 and the
      microsomal transfer protein. Physical exercise would interfere with the
      development of hepatic steatosis by stimulating lipid oxidation and inhibiting
      lipid synthesis in liver through the activation of the AMP-activated protein
      kinase pathway.

PMID- 16649141
TI  - Re-creating an RNA world.
AB  - The RNA world hypothesis states that life originated via a system based on RNA
      genomes and RNA catalysts. Researchers have been trying to develop such a system
      since catalytic RNAs (ribozymes) were discovered in 1982. This review summarizes
      the recent progress made in that endeavor and outlines the obstacles that remain
      to be overcome. After giving a short background on prebiotic chemistry and in
      vitro evolution, the discussion focuses on the generation of three important
      components of an RNA world: a sufficient polymerase ribozyme, self-replicating
      membrane compartments and ribozymes that are capable of performing basic
      metabolic processes.

PMID- 16649142
TI  - The life cycle of neutral lipids: synthesis, storage and degradation.
AB  - Triacylglycerols (TAGs), steryl esters (SEs) and wax esters (WEs) form the group
      of neutral lipids. Whereas TAGs are present in all types of cell, the occurrence
      of SEs in prokaryotes is questionable, and the presence of WEs as storage
      molecules is restricted to plants and a few bacteria. Here, we summarize recent
      knowledge on the formation, storage and degradation of TAGs and SEs in various
      cell types. We describe the biochemical pathways involved in TAG and SE synthesis
      and discuss the subcellular compartmentation of these processes. Recently,
      several novel enzymes governing the metabolism of storage lipids have been
      identified and characterized. Regulatory aspects of neutral lipid storage are
      just beginning to be understood. Finally, we describe consequences of defects in
      neutral lipid metabolism. Since severe diseases like atherosclerosis, obesity and
      type 2 diabetes are caused by lipid accumulation, mechanisms underlying neutral
      lipid synthesis, depot formation and mobilization are of major interest for
      curing such diseases that are increasingly associated with modern civilization.

PMID- 16649143
TI  - Caenorhabditis elegans dpy-5 is a cuticle procollagen processed by a proprotein
      convertase.
AB  - Genetic analysis of the nematode Caenorhabditis elegans reveals that all dpy-5
      alleles are dominant suppressors of bli-4 blistering. Molecular cloning of dpy-5
      establishes that it encodes a cuticle procollagen, defects in which are
      responsible for the short-body, dumpy phenotype. The null mutation, e907 removes
      the entire coding region, whereas the dpy-5 reference allele, e61, contains a
      nonsense substitution. RT-PCR analysis and a dpy-5::gfp fusion show that dpy-5 is
      expressed only in hypodermal cells at all post-embryonic life-cycle stages.
      Variable expression of dpy-5 in V lineage-derived seam cells suggests an
      alternative regulatory mechanism in these cells. The dpy-5 gene product contains
      an Arg-X-X-Arg cleavage motif that could be recognized by a proprotein
      convertase, such as BLI-4. Mutation of this site cause a dominant dumpy phenotype
      suggesting Dpy-5 procollagen requires processing for normal cuticle production.

PMID- 16649144
TI  - Back to the roots: the remarkable RAF oncogene story.
AB  - RAF kinases entered the limelight when our understanding of the genetic nature of
      cancer was much less defined and the seminal importance of proto-oncogenes as
      components of intracellular signaling pathways was just beginning to be
      recognized. Following the discovery of the v-RAF oncogene and the subsequent
      description of the c-RAF-1 gene by the group of Ulf Rapp, the last 20 years have
      seen the dissection of the signaling pathways in which RAF kinases function, and
      the cellular processes they control. The recent demonstration of mutations in B
      RAF and C-RAF in human tumors marked the return of RAF kinases to their roots as
      oncogenes. The availability of small molecular weight inhibitors has fueled the
      hope for new therapeutic approaches. Despite the deep insights gained through the
      work of many laboratories, the past has left us with sufficient controversy and
      plenty of open questions to keep RAF research as interesting as ever.

PMID- 16649145
TI  - Type I phosphoinositide 3-kinases: potential antithrombotic targets?
AB  - Arterial thrombosis is the single most common cause of death and disability in
      industrialized societies and is the primary pathogenic mechanism underlying acute
      myocardial infarction and ischemic stroke. Platelets play a central role in this
      process, and as a consequence, a great deal of effort has gone into identifying
      the mechanisms regulating the adhesive function of platelets. Platelet adhesion
      is controlled by intracellular signaling pathways, with growing evidence for a
      major role for phosphoinositide 3-kinases (PI3Ks) in this process. Platelets
      express all type I PI3K isoforms, including p110alpha, p110beta, p110delta and
      p110gamma, with recent evidence suggesting important roles for p110gamma and
      p110beta in regulating distinct phases of the platelet activation process.
      Deficiency of p110 gamma or inhibition of p110beta produces a marked defect in
      arterial thrombosis without a corresponding increase in bleeding time, raising
      the possibility that inhibition of one or more PI3K isoforms may represent an
      effective antithrombotic approach.

PMID- 16649146
TI  - The design of intracellular oscillators that interact with metabolism.
AB  - Biological oscillations such as circadian rhythms are ubiquitous in nature and
      have attracted significant attention because of their intriguing dynamics and
      important biological roles. Understanding of such sophisticated and robust
      oscillators requires more than the traditional reductionist approach. Recently, a
      synthetic approach similar to the design of engineering machinery has provided a
      valuable alternative for testing hypothetical operating principles. These man
      made genetic circuits and gene-metabolic circuits are designed based on physical
      concepts, guided by mathematical models, and constrained by biological and
      chemical reality. While still primitive compared with the natural circuits, the
      designed gene-metabolic oscillator has begun to show hallmarks of circadian
      rhythms such as temperature compensation and close interaction with metabolism.

PMID- 16649147
TI  - [Gonorrhoea and chlamydia infections during pregnancy].

PMID- 16649148
TI  - [Prevention of puerperal fever--history of its discovery].

PMID- 16649149
TI  - [Guidelines for the diagnosis and treatment of group B streptococcal colonization
      during pregnancy and delivery. Perinatal medicine section of the CGPS CLS JEP].

PMID- 16649150
TI  - [Issues of congenital syphilis in the past twenty years. I. Etiology,
      epidemiology and diagnosis].
AB  - Since 1990 there is an upward trend in the incidence of both acquired and
      congenital syphilis in the Czech Republic. A similar situation exists in other
      European countries as well. Higher incidence of syphilis is clearly associated
      with urban agglomerates and sexual tourism destinations. The only way to reduce
      the number of cases is a consistent application of mandatory preventive and
      diagnostic measures. These important measures against the spreading of the
      infection include mandatory serological testing of pregnant women and newborns
      (from umbilical blood), antibiotic treatment and systematic follow-up of HIV
      positive mothers and children. This paper describes the current epidemiological
      situation of syphilis in the Czech Republic and presents a review of available
      diagnostic tests and their significance for diagnosis.

PMID- 16649151
TI  - [Issues of congenital syphilis in the past twenty years. II. Clinical picture].
AB  - The paper describes the clinical picture and management of congenital syphilis.
      In the introduction the origin of syphilis is mentioned. The etiologic agent --
      Treponema pallidum subsp. pallidum (Tp) -- is transmitted to fetus almost
      exclusively via placenta. Perinatal infections are less frequent, and postnatal
      infections are only exceptionally. The symptoms of congenital syphilis may be
      divided into prenatal (syphilis materno-fetalis), neonatal, and rarely seen
      postnatal. Prenatal symptoms causing the immaturity of fetus are recognizable
      from the 7th month of pregnancy and associated with miscarriages, premature
      deliveries of still-born babies or live neonates with congenital syphilis.
      Neonatal and postnatal symptoms are manifested only after birth. They may present
      immediately at birth, develop within first two years of life as early congenital
      syphilis, or (similarly to acquired syphilis) later in life as a late localized
      form, often seen many years after birth, even at puberty -- late congenital
      syphilis. The clinical picture depends on many factors -- primarily on the
      duration of the infection in mother and the stage of pregnancy.

PMID- 16649152
TI  - [Mother-to-child HIV transmission].
AB  - Vertical HIV transmission is the main route of infection in children. The vast
      majority of infected children are born in the developing world. In the developed
      countries, including the Czech Republic, the situation is relatively favourable
      thanks to preventive activities and effective prophylactic measures in HIV
      positive pregnant women. The risk of vertical transmission depends on a number of
      maternal (including immunological), virological, obstetric, feto-placental and
      neonatal factors. The basic prophylactic steps are: administration of
      antiretroviral agents, delivery by Caesarean section and avoidance of breast
      feeding. Diagnosis of HIV infection in children relies on direct virological
      diagnosis -- the demonstration of the absence of viral genome in blood samples
      taken at the age of 2-3 and 4-6 months is crucial for excluding vertical
      infection. In the first 6 weeks of life, children receive the zidovudine
      prophylaxis. From the age of 6-8 weeks until approx. 6 months, children in whom
      HIV infection has not been excluded are on the primary co-trimoxazole prophylaxis
      of Pneumocystis infection.

PMID- 16649153
TI  - [Prophylaxis of the vertical transmission of the human immunodeficiency virus
      (HIV) in the Czech Republic].
AB  - GOAL: To assess the efficacy of prophylactic measures intended to reduce vertical
      transmission of HIV infection and to evaluate the predictive value of
      demographic, immunological and virological factors for determination of the risk
      of HIV transmission to fetus and neonate. METHODS: 56 pregnancies of 53 HIV
      positive women were included in this retrospective study. The women have been in
      the care of the AIDS Centre of the Dpt. of Infectious Diseases, University
      Hospital Na Bulovce over the past 15 years. Cellular immunity tests and HIV RNA
      viral load in all subjects were regularly determined. In line with our present
      knowledge and the patients compliance, we introduced prophylactic measures, which
      included the administration of antiretroviral agents, delivery by Caesarean
      section and breast-feeding avoidance. 58 children were born from these
      pregnancies and repeated blood tests were performed to detect the presence or
      absence of HIV RNA. RESULTS: 58 infants were born from 56 pregnancies-and 3 of
      them (5.17%) were infected with HIV. In two mothers, we diagnosed HIV positivity
      few hours before delivery; another woman was diagnosed early, however, the
      failure of treatment was due to her insufficient compliance. In addition,
      premature amniorrhoea was present in two women. Moreover, one of them presented
      with untreated syphilis. The other 55 children stayed uninfected. In six of them,
      however, prophylactic measures were not fully followed, mainly because the
      patients disregarded them. CONCLUSIONS: The study fully confirms the high
      efficacy of prophylactic measures, which substantially reduce the risk of
      vertical transmission of HIV infection. Routine blood tests are necessary in all
      pregnant women by law. The failure of prophylaxis is in most cases due to
      inadequate compliance with the treatment. However, we cannot rule out the
      possible resistance to antiretroviral agents.

PMID- 16649154
TI  - Dispersal and species diversity: a meta-analysis.
AB  - Species diversity in communities of interacting organisms is thought to be
      enhanced by dispersal, yet mechanisms predicting this have little to say about
      what effects differing rates of dispersal have on diversity and how dispersal
      affects diversity at larger spatial scales. I performed meta-analyses on 23
      studies comprising 50 experiments that manipulated species migration and measured
      community richness or diversity to test three hypotheses: that dispersal
      increases local diversity; that this effect depends on the rate of dispersal,
      specifically, that local diversity should be maximized at intermediate dispersal
      rates or else linearly related to dispersal rate; and that regional diversity may
      be either unaffected or negatively impacted by dispersal because dispersal tends
      to homogenize local communities. I found that immigration increased local
      diversity. Further, in animal studies, diversity appears maximized at
      intermediate dispersal rates but not with plant studies; however, more
      standardized studies are needed. Finally, results are ambiguous as to what
      happens at larger scales, with studies finding either declines or no change in
      regional diversity with dispersal. Taken together, these results reveal that
      dispersal has a complex, spatially contingent relationship with patterns of
      species diversity.

PMID- 16649155
TI  - Pereskia and the origin of the cactus life-form.
AB  - The cactus life-form is cited as an example of a tight relationship between
      organism form and function: a succulent, long-lived, photosynthetic stem allows
      cacti to survive long periods of drought while maintaining a positive tissue
      water status. Pereskia (Cactaceae) comprises 17 species of leafy shrubs and trees
      that are thought to represent the original cactus condition. Recent phylogenetic
      work has shown that there are two separate clades of Pereskia species, which are
      basal and paraphyletic with respect to the rest of the cacti. We selected seven
      Pereskia species, representing both clades, and characterized their water
      relations by measuring a suite of physiological traits in wild populations.
      Additionally, we estimated basic climate parameters from collection localities
      for all 17 Pereskia species. Extant Pereskia species exhibit ecological water use
      patterns that are very similar to those of the leafless, stem-succulent cacti.
      Ancestral trait reconstruction for the physiological and environmental data
      provides a preliminary assessment of the ecology and water relations of the
      earliest cacti and suggests that several key elements of the cactus ecological
      niche were established before the evolution of the cactus life-form. We interpret
      these ecological traits as potentially important drivers of evolutionary
      innovation in the cacti.

PMID- 16649156
TI  - Predation risk as a driving force for sexual segregation: a cross-population
      comparison.
AB  - Sexual segregation is widespread throughout the animal kingdom. Although a number
      of hypotheses have been proposed to account for observed patterns, the generality
      of the mechanisms remains debated. One possible reason for this is the focus on
      segregation patterns in large mammals such as ungulates, where the majority of
      studies are descriptions of a single population. Here, we present the results of
      a cross-population comparison of patterns of sexual segregation in the
      Trinidadian guppy, Poecilia reticulata. We relate observed patterns to
      experimental quantification of predation risk and sexual harassment of females by
      males in eight populations. We find that the degree of segregation increases with
      predation risk, with deeper waters becoming increasingly female biased.
      Furthermore, we observed that levels of male harassment are lower in deeper water
      but only in those rivers that contain major guppy predators. We conclude that
      sexual segregation in guppies is consistent with the predation risk hypothesis:
      sexual segregation results from a combination of predation risk driving males
      (the more vulnerable sex) into less risky habitats and females gaining benefits
      of reduced sexual harassment by remaining in high-predation environments.

PMID- 16649157
TI  - Adaptive introgression of herbivore resistance traits in the weedy sunflower
      Helianthus annuus.
AB  - The role of hybridization in adaptive evolution is contentious. While many cases
      of adaptive trait introgression have been proposed, the relevant traits have
      rarely been identified, resulting in a lack of clear examples of this process.
      Here, we examine a purported case of adaptive introgression in which the annual
      sunflower Helianthus annuus annuus has captured alleles from a congener
      (Helianthus debilis) to form a stabilized hybrid, Helianthus annuus texanus. We
      tested the hypotheses that herbivore resistance traits have introgressed from H.
      debilis to H. annuus and have increased adaptation in the latter. In two common
      gardens, fitness (estimated by seed production) was on average 55% higher in H.
      a. texanus than in H. a. annuus. For H. a. texanus, three damage traits (of seven
      tested) differed significantly from the H. a. annuus parent in one or both sites
      and were shifted in the direction of the more resistant H. debilis. Natural
      selection favored H. a. annuusxH. debilis BC(1) hybrids (synthesized to mimic the
      ancestors of H. a. texanus) with H. debilis-like resistance to seed midges
      Neolasioptera helianthis and to receptacle/seed feeding Lepidoptera at one or
      both sites. Assuming similar herbivore pressures in the past, these results
      suggest that introgression of biotic resistance traits was important in the
      adaptation of H. annuus to central and southern Texas.

PMID- 16649158
TI  - Synthesis and anticoagulant activities of substituted 2,4-diketochromans,
      biscoumarins, and chromanocoumarins.
AB  - Different substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins are
      the final products when 4-hydroxycoumarin and aromatic aldehydes containing
      hydroxyl group in o-, m,- or p-position condense in boiling ethanol. We
      synthesized 14 compounds. Three of them are described for the first time. The X
      ray crystal structure analysis of 3-[6-oxo-(6H, 7H)-benzopyrano[4,3-b]benzopyran
      7-yl]-4-hydroxy-2H-1-benzopyran-2-one 1 confirmed the structure of this compound.
      Acute toxicity studies of the compounds were performed on mice by oral and
      intraperitoneal administration. A comparative pharmacological study of the in
      vivo anticoagulant effect of the derivatives with respect to warfarin showed that
      the synthesized compounds have different anticoagulant activities. The most
      prospective compounds are 3-(3'-hydroxybenzylidene)-2,4-diketochroman 4 and 3,3'
      (2-pyridylmethylene)-bis-4-hydroxy-2H-1-benzopyran-2-one 11 with low toxicity and
      dose-dependent anticoagulant activity in vivo.

PMID- 16649159
TI  - Synthesis and molluscicidal activity of some 1,3,4-triaryl-5-chloropyrazole,
      pyrano[2,3-c]pyrazole, pyrazolylphthalazine and pyrano[2,3-d]thiazole
      derivatives.
AB  - 2-(5-Chloro-1,3-diphenyl-1H-pyrazol-4-ylmethylene)-malononitrile 1a reacts with
      the arylidenes of malononitrile 2a-d to afford the triaryl-5-chloropyrazoles 3a
      d, respectively. 1a reacts with the active methylene pyrazolinones 5a, b and 12a,
      b to afford different products 8, 9, 10, 11, and 14a, b--depending on the
      substitution in the pyrazole ring. Compound 1a reacts also with the pyridazinone
      derivative 15 to afford the phthalazinone 16, and with the thiazolinones 17a-c to
      afford the pyrano[2,3-d]thiazoles 20a-c, respectively. It reacts also with the
      malononitrile dimer 21a and with ethyl cyanoacetate dimer 21b to yield the
      pyrazolyl pyridines 22a, b, respectively. The synthesized compounds showed a
      moderate molluscicidal activity towards Biomphalaria alexandrina snails.

PMID- 16649160
TI  - Design, synthesis, and calcium channel antagonist activity of new 1,4
      dihydropyridines containing 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent.
AB  - A series of dialkyl, dicycloalkyl, and diaryl ester analogues of nifedipine, in
      which the ortho-nitro phenyl group at position 4 is replaced by the 4-(5)-chloro
      2-ethyl-5-(4)-imidazolyl substituent, were synthesized and evaluated as calcium
      channel antagonists using the high K+ contraction of guinea pig ileal
      longitudinal smooth muscle. The results for the symmetrical ester series showed
      that increasing the length of the chain in C3- and C5-ester substituents
      increased the activity and the most active compound was the diphenylethyl ester
      derivative, so it was more active than the reference drug nifedipine. In
      unsymmetrical diester series, when R1 is methyl or ethyl, increasing lipophilic
      properties in the R substituent, increased the activity. The most active
      compounds were methyl/phenethyl and ethyl/phenethyl ester derivatives, being
      slightly more active than nifedipine.

PMID- 16649161
TI  - Inflammation inhibitors were remarkably up-regulated in plasma of severe acute
      respiratory syndrome patients at progressive phase.
AB  - Severe acute respiratory syndrome (SARS) is a severe infectious disease that has
      affected many countries and regions since 2002. A novel member of the
      coronavirus, SARS-CoV, has been identified as the causative agent. However, the
      pathogenesis of SARS is still elusive. In this study, we used 2-D DIGE and MS to
      analyze the protein profiles of plasma from SARS patients, in the search for
      proteomic alterations associated with the disease progression, which could
      provide some clues to the pathogenesis. To enrich the low-abundance proteins in
      human plasma, two highly abundant proteins, albumin and IgG, were first removed.
      By comparing the plasma proteins of SARS patients with those of a normal control
      group, several proteins with a significant alteration were found. The up
      regulated proteins were identified as alpha-1 acid glycoprotein, haptoglobin,
      alpha-1 anti-chymotrypsin and fetuin. The down-regulated proteins were
      apolipoprotein A-I, transferrin and transthyretin. Most of the proteins showed
      significant changes (up- or down-regulated) in the progressive phase of disease,
      and there was a trend back to normal level during the convalescent phase. Among
      these proteins, the alterations of fetuin and anti-chymotrypsin were further
      confirmed by Western blotting. Since all the up-regulated proteins identified
      above are well-known inflammation inhibitors, these results strongly suggest that
      the body starts inflammation inhibition to sustain the inflammatory response
      balance in the progression of SARS.

PMID- 16649166
TI  - Bridging Proteomics and Medical Science - the 5th HUPO Brain Proteome Workshop in
      Dublin, Ireland.
AB  - More than 70 interested colleagues attended the 5th Workshop of the HUPO Brain
      Proteome Project (HUPO BPP) at the UCD Conway Institute, Dublin, Ireland. An
      overview of the outcome of the pilot study was presented and the new subprojects
      "Clinical Neuroproteomics of Human Body Fluids" as well as "Cerebellum 2D
      mapping" were announced. In addition the election of the HUPO BPP committees and
      the future directions of this project were discussed and decided. The meeting was
      enhanced by several talks highlighting the application of proteomics in
      biomedical research.

PMID- 16649167
TI  - Applications of highly sensitive phosphopeptide derivatization methods without
      the need for organic solvents.
AB  - Detection and identification of phosphorylated amino acid residues is still one
      of the most challenging tasks in contemporary protein analysis. Especially serine
      and threonine-phosphorylation is very often involved in the regulation of enzyme
      activities and regulates key functions in cellular processes.

PMID- 16649168
TI  - Patterning the heart, a template for human cardiomyocyte development.
AB  - Although in mice, the dynamics of gene expression during heart development is
      well characterized, information on humans is scarce due to the limited
      availability of material. Here, we analyzed the transcriptional distribution of
      Mlc-2a, Mlc-1v, Mlc-2v, and atrial natriuretic factor (ANF) in human embryonic
      hearts between 7 and 18 weeks of gestation and in healthy and hypertrophic adult
      hearts by in situ hybridization and compared expression with that in mice.
      Strikingly, Mlc-2a, Mlc-1v, and ANF, which are essentially chamber-restricted in
      mice by mid-gestation, showed a broader distribution in humans. On the other
      hand, Mlc-2v may prove to be an adequate ventricular marker in humans in contrast
      to mouse. This study emphasizes the importance of careful comparative human
      animal analyses during embryonic development and adulthood, as avoiding erroneous
      extrapolations may be critical to develop new and successful myocardial
      replacement therapies.

PMID- 16649169
TI  - Digital photogrammetry for quantitative wear analysis of retrieved TKA
      components.
AB  - The use of new materials in knee arthroplasty demands a way in which to
      accurately quantify wear in retrieved components. Methods such as damage scoring,
      coordinate measurement, and in vivo wear analysis have been used in the past. The
      limitations in these methods illustrate a need for a different methodology that
      can accurately quantify wear, which is relatively easy to perform and uses a
      minimal amount of expensive equipment. Off-the-shelf digital photogrammetry
      represents a potentially quick and easy alternative to what is readily available.
      Eighty tibial inserts were visually examined for front and backside wear and
      digitally photographed in the presence of two calibrated reference fields. All
      images were segmented (via manual and automated algorithms) using Adobe Photoshop
      and National Institute of Health ImageJ. Finally, wear was determined using
      ImageJ and Rhinoceros software. The absolute accuracy of the method and
      repeatability/reproducibility by different observers were measured in order to
      determine the uncertainty of wear measurements. To determine if variation in wear
      measurements was due to implant design, 35 implants of the three most prevalent
      designs were subjected to retrieval analysis. The overall accuracy of area
      measurements was 97.8%. The error in automated segmentation was found to be
      significantly lower than that of manual segmentation. The photogrammetry method
      was found to be reasonably accurate and repeatable in measuring 2-D areas and
      applicable to determining wear. There was no significant variation in uncertainty
      detected among different implant designs. Photogrammetry has a broad range of
      applicability since it is size- and design-independent. A minimal amount of off
      the-shelf equipment is needed for the procedure and no proprietary knowledge of
      the implant is needed.

PMID- 16649170
TI  - A comparison of ProOsteon, DBX, and collagraft in a rabbit model.
AB  - Many bone graft substitutes (BGSs) have been developed and are commercially
      available. These products differ in the tailoring of their properties, including
      size, form, osteoconductivity, osteoinductivity, and resorption kinetics.
      Differential enhancement of these properties may optimize the performance of
      these materials for varying applications. BGSs offer an opportunity to lessen
      morbidity of harvesting and use of autogenous and/or allograft bone. The purpose
      of this study is to quantitatively compare the magnitude of bony ingrowth and
      biodegradation of different commercially available BGS materials in a rabbit
      femoral defect model. BGSs from each of three classes (ceramic (ProOsteon),
      demineralized bone matrix (DBX), and composite (Collagraft)) were implanted in
      cylindrical defects in bilateral femoral condyles of 12 adult New Zealand White
      rabbits. Each of the three BGS materials and the empty controls were compared.
      The specimens were harvested at 3 months postimplantation for radiographic and
      histologic evaluation. Histomorphometry yielded resorption of graft material
      remaining in the index defect. Magnitude of bony ingrowth was assessed based on
      an 8-bit 256 densitometry model. Histomorphometric analysis of the data
      demonstrated statistical differences in the resorption and magnitude of bony
      ingrowth of the three BGS materials. The three BGS were significantly different
      for ingrowth (p = 0.046) when using the Wilcoxon Test. The ceramic graft material
      averaged 47% bony ingrowth. Rabbit-based DBX material showed extensive osseous
      ingrowth (35%) and the composite graft material demonstrated significant bony
      ingrowth (56%). The control, as anticipated, showed the least amount of bony
      ingrowth (29%). Fisher's Exact Test yielded statistical differences (p = 0.0003)
      when comparisons for resorption were conducted. An ideal BGS material should be
      biocompatible, be able to withstand the local load environment for a given
      application, degrade in concert with bony replacement, and be both osteoinductive
      and osteoconductive. This in-vivo, head-to-head comparison of three commercially
      available BGS materials in an animal model compares these characteristics and
      demonstrates differences between them, which may act as a guide in the use of
      these products in human applications.

PMID- 16649171
TI  - A novel polymer for potential use in a trileaflet heart valve.
AB  - A novel polyolefin, poly(styrene-b-isobutylene-b-styrene) (Quatromer), is being
      proposed as a viable polymer for use in trileaflet heart valves because of its
      oxidative stability. The current study was designed to assess the polymer's
      hemocompatibility and mechanical durability. Mechanical characterization included
      static tensile tests and dynamic tension-tension and bending fatigue tests, where
      the properties of isotropic and composite (polypropylene (PP) embedded) Quatromer
      specimens were compared with those of a polyurethane (PUR) approved for
      cardiovascular applications. It was found that by embedding PP fibers into the
      Quatromer matrix, the tensile and fatigue properties of the polymer could be
      improved, making them comparable, if not better than the PUR. The thrombotic
      potential of Quatromer was compared with the PUR, glutaraldehyde-fixed porcine
      valve material, and a positive and negative control by measuring platelet
      deposition with radiolabeled platelets in a parallel plate flow configuration.
      The porcine valve material was found to have significantly higher platelet
      deposition under all flow regimes, while no significant difference existed
      between Quatromer and PUR. In conclusion, Quatromer is shown to have suitable
      hemocompatibility and mechanical durability for use in polymer trileaflet heart
      valves, and fiber reinforcement can effectively be used to tailor the mechanical
      properties.

PMID- 16649172
TI  - The effect of self-designed bifunctional RGD-containing fusion protein on the
      behavior of human keratinocytes and dermal fibroblasts.
AB  - In this study, self-designed bifunctional RGD-containing fusion protein (BFP) was
      grafted on the petri dish to evaluate its cytotoxicity and attachment efficiency
      on primary cultured keratinocytes and dermal fibroblasts. Two lengths of the
      GRGDS sequences were separately fused to the N-terminus and C-terminus of the
      Trichoderma koningii cellobiohydrolase I gene cellulose-binding domain, to serve
      as linking molecule between the cell and the substrate. The grafting procedure
      was no more labor-intensive and could be done just in aqueous condition itself.
      The epidermal keratinocytes and dermal fibroblasts, harvested and separated from
      human foreskin, were cultured in serum-free keratinocyte culture medium and DMEM,
      respectively. The BFP was dissolved in double-deionized water, and was prepared
      at different concentrations. The BFP solution was subsequently added into the
      petri dish for grafting. MTT assay, total DNA measurement, and lactate
      dehydrogenase analysis were used to evaluate the cell viability, cell
      proliferation, and cytotoxicity. The immunochemical stain and SEM examination
      were chosen to make sure that the cultured cells still kept in phenotype. The
      results showed that the self-designed BFP was successfully coated on the petri
      dish to improve the cells' adhesion. The whole coating procedure was just done in
      aqueous solution without any organic solvent being involved. This method was much
      simpler than the traditional one, and there was no possibility to damage the
      immobilized biomolecules. From the results of the study, BFP could enhance
      attachment of keratinocytes and dermal fibroblasts without losing normal cell
      morphology and keep keratinocytes on the desired differentiation pathway. We
      believe that coating BFP on petri dish not only enhanced the keratinocyte
      attachment but also promoted keratinocytes proliferation. We suggest that the
      self-designed BFP has a great potential to apply on surface modification for the
      tissue-engineering scaffolds in the future.

PMID- 16649173
TI  - Controlling delivery properties of a waterborne, in-situ-forming biomaterial.
AB  - This study details efforts to transition an in-situ-gelling polymer for
      endovascular embolization from the bench-top to preclinical cerebral
      arteriovenous malformation animal model studies. The in-situ-forming gel is based
      on waterborne, reverse emulsion materials. For controlled embolization of
      vascular defects, it is crucial to understand the delivery properties of an in
      situ-forming gel. Directing a liquid into a small cavity requires both precise
      control of the fluid flow, and depends upon minimal variability in the materials
      behavior. A 2(3) factorial experiment performed in the laboratory revealed that
      temperature, mixing time, and buffer strength are all significant factors
      affecting the gelation time of the specific system studied. All three factors
      were also seen to reduce the standard deviation on the gel times. Changing the
      temperature from 21.3 to 37.0 degrees C reduced the cross population variability
      from 6.0 +/- 3.3 min to 3.4 +/- 1.6 min. At 30-s premixing, the protocol produced
      an average gel time of 5.3 +/- 3.0 min, which was reduced to 3.3 +/- 1.2 min with
      90 s. Finally, a 50 mM buffer solution provided a gel time of 6.5 +/- 3.2 min,
      which was reduced to 2.95 +/- 0.6 min at 100 mM. Viscosity data was analyzed to
      suggest a model for injection volume and viscosity.

PMID- 16649174
TI  - Film from peroxidation of an amino phospholipid and its biocompatibility.
AB  - A new kind of phospholipid product with fluorescence was derived from
      autoxidation of an aminophospholipid, L-alpha-phosphatidylethanolamine
      dilinoleoyl in solid film state. Atomic force microscopy showed that the film
      product was composed of round and elliptical vesicles with diameters of about 20
      45 nm. The product was difficult to dissolve in water and most organic solvents.
      Fourier transform infrared spectroscopy, solid-state (13)C NMR, and solid-state
      (31)P NMR indicated that the unsaturated double carbon bond decreased with the
      reaction, and polymerization within/between phospholipid molecules occurred.
      Endothelial cells from human vein seeded onto the film showed the highest
      proliferating activity compared with seeding onto Corning culture plate, glass
      plate, or phospholipid film with phosphorylcholine head group, as evaluated by 3
      (4,5-timethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (p < 0.001).
      The hemocompatibility of the film was also assessed by platelet adhesion and
      protein adsorption. The results suggest that the product has potential
      applications as a new biomaterial coating.

PMID- 16649175
TI  - Porous hybrid structures based on P(DLLA-co-TMC) and collagen for tissue
      engineering of small-diameter blood vessels.
AB  - Poly (D,L-lactide)-7co-(1,3-trimethylene carbonate) [P(DLLA-co-TMC)] (83 mol %
      DLLA) was used to produce matrices suitable for tissue engineering of small
      diameter blood vessels. The copolymer was processed into tubular structures with
      a porosity of approximately 98% by melt spinning and fiber winding, thus
      obviating the need of organic solvents that may compromise subsequent cell
      culture. Unexpectedly, incubation in culture medium at 37 degrees C resulted in
      disconnection of the contact points between the polymer fibers. To improve the
      structural stability of these P(DLLA-co-TMC) scaffolds, a collagen microsponge
      was formed inside the pores of the synthetic matrix by dip coating and freeze
      drying. Hybrid structures with a porosity of 97% and an average pore size of 102
      mum were obtained. Structural stability was preserved during incubation in
      culture medium at 37 degrees C. Smooth-muscle cells (SMCs) were seeded in these
      hybrid scaffolds and cultured under pulsatile flow conditions in a bioreactor
      (120 beats/min, 80-120 mmHg). After 7 days of culture in a dynamic environment
      viable SMCs were homogeneously distributed throughout the constructs, which were
      five times stronger and stiffer than noncultured scaffolds. Values for yield
      stress (2.8 +/- 0.6 MPa), stiffness (1.6 +/- 0.4 MPa), and yield strain (120% +/-
      20%) were comparable to those of the human artery mesenterica.

PMID- 16649177
TI  - Correlation of swelling pressure and intrafibrillar water in young and aged human
      intervertebral discs.
AB  - Fluid balance in the intervertebral disc under applied load is determined
      primarily by its swelling pressure, that is, the external pressure at which it
      neither loses nor gains water. This depends on the composition of the tissue, in
      particular on its proteoglycan concentration. Proteoglycans develop a high
      osmotic pressure due to their fixed negatively charged groups. Because of their
      size, proteoglycans are excluded from the collagen's intrafibrillar volume; hence
      their osmotic activity is determined only by the extrafibrillar water. Here, we
      show that in order to evaluate correctly the swelling pressure in the annuli
      fibrosi of human intervertebral disc, it is essential to evaluate its proportion
      of intrafibrillar water. We used low-angle X-ray scattering and osmotic stress
      techniques to determine the lateral packing of the collagen molecules in the
      fibrils of the annuli fibrosi (ages: 25-77). It was found that the lateral
      packing and, hence, the intrafibrillar water content depends on age, external
      osmotic pressure, and location in the tissue. Subtracting intrafibrillar water
      from total hydration yields the amount of extrafibrillar water, from which the
      true fixed charge density of the tissue could be estimated. From a force balance,
      it would appear that collagen tension plays only a minor role in the equilibrium
      of the human intervertebral disc under load, in contrast to articular cartilage,
      where collagen tension is important for load bearing.

PMID- 16649178
TI  - Pathophysiological advantages of rinsing-suction-reaming (RSR) in a pig model for
      intramedullary nailing.
AB  - Although reamed intramedullary nailing has been one of the greatest advances in
      modern fracture care, the concomitant increase in medullary cavity pressure leads
      to intravasation of bone marrow content into the blood stream, an effect that can
      evoke serious systemic reactions. A newly developed rinsing-suction-reamer (RSR)
      was able to substantially reduce the pressure and bone marrow intravasation
      content during experimental femoral nailing. We investigated the
      pathophysiological effects using the RSR, testing the hypothesis that by reducing
      marrow fat embolization, RSR would also reduce the activation of coagulation
      compared with the universal AO-Reamer (AOR) and comparable to external fixation.
      Twenty-two pigs were treated with either simulated external fixation or reamed
      femoral nailing using AOR or RSR. During surgery, the intramedullary pressure was
      measured and intravasation of medullary material was quantified. After surgery,
      the pigs were kept anaesthetised and monitored for 6 h. At defined intervals,
      serological, hematological, and hemodynamic parameters were evaluated. The RSR
      was significantly superior when compared to AOR with regard to the generation of
      intramedullary pressure and fat embolization; however, with external fixation the
      values were even lower. The evaluation of other parameters revealed no clear
      differences between the two reamers and the external fixator. The pig model
      showed that RSR led to a significant reduction of the intramedullary increase in
      pressure and fat intravasation compared to AOR. Although the reduction of fat
      embolism by RSR is not associated with pathophysiological changes, RSR can have
      advantages for the treatment of femoral fractures.

PMID- 16649179
TI  - Opioid peptides and receptors in joint tissues: study in the rat.
AB  - Using immunohistochemical and biochemical techniques, the occurrence of
      endogenous opioid peptides and their receptors in normal rat bone and joint
      tissues was investigated. Opioid receptors were detected, quantified, and
      characterized in homogenates from capsule/synovium and periosteum using
      radioligand binding assays. Receptor binding of the nonselective opioid
      [3H]naloxone to tissue homogenates was stereospecific and saturable, showing
      similar characteristics to that of brain tissue, although with lower binding
      capacities. By immunohistochemistry, the neuronal occurrence of four different
      enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta
      articular bone, whereas no neuronal dynorphin immunoreactivity was detected.
      Double-staining studies disclosed that enkephalins coexisted with substance P in
      primary afferent fibers. The applied techniques can be used to assess changes in
      the distribution of endogenous opioids and their receptors in joint tissues in
      conditions associated with pain and inflammation. The endogenous opioid system
      now demonstrated might be targeted and exploited therapeutically to obtain
      peripheral control of symptoms in joint disorders.

PMID- 16649180
TI  - Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic
      proteins-2 or -6.
AB  - Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted
      osteogenic differentiation and can be augmented by delivery of genes encoding
      bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic
      differentiation of BMDMSC was investigated using two BMP genes in monolayer and
      three-dimensional alginate culture systems. Cultured BMDMSC were transduced with
      E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding
      sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of
      infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2%
      alginate beads for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction
      resulted in abundant BMP-2 and BMP-6 mRNA and protein expression in monolayer
      culture and BMP-2 protein expression in alginate cultures. Ad-BMP-2 and Ad-BMP-6
      transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase
      positive staining and mineralization and were sustained for a longer duration
      with better morphology scores than untransduced or Ad-beta-galactosidase
      transduced cells. Ad-BMP-2- and, to a lesser degree, Ad-BMP-6-transduced BMDMSC
      suspended in alginate demonstrated greater mineralization than untransduced
      cells. Gene expression studies at day 2 confirmed an inflammatory response to the
      gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation
      of genes consistent with response to BMP exposure and osteogenic differentiation,
      specifically endochondral ossification and extracellular matrix proteins,
      occurred in BMP-transduced cells. These data support that transduction of BMDMSC
      with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and
      mineralization of stem cells in culture, including in three-dimensional culture.
      BMP-2-transduced stem cells suspended in alginate culture may be a practical
      carrier system to support bone formation in vivo. BMP-6 induced a less robust
      cellular response than BMP-2, particularly in alginate culture.

PMID- 16649181
TI  - Effect of particle size of an amorphous calcium phosphate filler on the
      mechanical strength and ion release of polymeric composites.
AB  - The random clustering of amorphous calcium phosphate (ACP) particles within resin
      matrices is thought to diminish the strength of their polymerized composites. The
      objective of this study was to elucidate the effect of ball-milling on the
      particle size distribution (PSD) of ACP fillers and assess if improved dispersion
      of milled ACP in methacrylate resin sufficiently enhanced filler/matrix
      interactions to result in improved biaxial flexure strength (BFS), without
      compromising the remineralizing potential of the composites. Unmilled and wet
      milled zirconia-hybridized ACP (Zr-ACP) fillers were characterized by PSD
      analysis, X-ray diffraction, thermogravimetric and chemical analysis, infrared
      spectroscopy, and scanning electron microscopy. Composite specimens made from a
      photoactivated, ternary methacrylate resin admixed with a mass fraction of 40% of
      un-milled or milled Zr-ACP were evaluated for the BFS (dry and wet) and for the
      release of calcium and phosphate ions into saline solutions. While having no
      apparent effect on the structure, composition, and morphology/topology of the
      fillers, milling significantly reduced the average size of Zr-ACP particulates
      (median diameter, d(m) = 0.9 +/- 0.2 microm) and the spread of their PSD. Better
      dispersion of milled Zr-ACP in the resins resulted in the improved BFS of the
      composites, even after aqueous soaking, and also gave a satisfactory ion release
      profile. The demonstrated improvement in the mechanical stability of anti
      demineralizing/remineralizing ACP composites based on milled Zr-ACP filler may be
      beneficial in potentially extending their dental utility.

PMID- 16649182
TI  - Modification of HTPB-based polyurethane with temperature-sensitive poly(N
      isopropyl acrylamide) for biomaterial usage.
AB  - Hydroxyl-terminated polybutadiene (HTPB)-based polyurethane with dimethyol
      propionic acid (DPA) as chain extender was synthesized by solution
      polymerization. The HTPB-based polyurethane was modified by UV radiation with N
      isopropyl acrylamide monomer to get poly(N-isopropyl acrylamide)-modified
      polyurethane (PUDPANIPAAm). The cohesive energy (E(coh)), molar volume (V),
      solubility parameter (delta), molecular weight (W(M)), volume per gram (V(g)),
      and the density (1/V(g)) of PUDPANIPAAm were calculated by group contribution
      methods. To evaluate the application of PUDPANIPAAm for wound dressing and
      transplantation of cell sheet, the measurement of water content, water vapor
      transmission rate, and gas permeation on the PUDPANIPAAm membrane was evaluated.
      The biocompatibility of these membranes, cell adhesion, and proliferation assay
      were conducted in the cell culture. The effect of thermosensitivity of poly(N
      isopropyl acrylamide) on cell detachment was also evaluated in the primary study.
      The results showed that these PUDPANIPAAm membranes are thermosensitive. The
      modification of PU with poly(N-isopropyl acrylamide) reduced the water vapor
      transmission rate and permeability of gas through PUDPANIPAAm membrane.
      PUDPANIPAAm membranes could support cell adhesion and growth. Owing to the
      thermosensitive nature of poly(N-isopropyl acrylamide), the relative cell numbers
      detached from PUDPANIPAAm membranes were larger than those detached from the
      polystyrene dish.

PMID- 16649183
TI  - Diffusion-induced water movement within resin-dentin bonds during bonding.
AB  - It is thought that water-filled channels and nanovoids in resin-dentin bonds
      represent potential sites for degradation of bonds or hydrolysis of collagen or
      both. How water gains access to bonded interfaces is not clear. This study
      evaluated the diffusion-induced water uptake through resin-dentin interfaces
      during bonding. Two light-cured total-etch adhesive systems (Excite and One-Step
      Plus) and a chemical-cured adhesive (Amalgambond Plus) were used in this study.
      Dentin disks were placed in a split-chamber device, and the fluid movement across
      dentin was measured, with and without a physiological pressure, during bonding
      procedures and 24 h after bonding. For light-cured adhesives in the experimental
      groups, a 6 min interval of dark storage was conducted prior to light-curing, to
      evaluate the diffusion of water through the uncured resin monomers, and to test
      the effect of prolonged infiltration time of adhesives on water permeability of
      bonds. Prolonged adhesive infiltration reduced the water permeability of resin
      dentin bonds for light-cured adhesives. Water gradients produced by bonding
      systems contribute to water movement across the dentin-adhesive interfaces during
      bonding procedures. Differences in chemical formulations for adhesive systems may
      lead to differences in the extent of diffusion-induced water movement and the
      amount of water within the resin-dentin bonds.

PMID- 16649184
TI  - Polymerization kinetics and mechanical characterization of new formulations of
      light-cured dental sealants.
AB  - The aim of the study was to develop and evaluate the in vitro performance of a
      new and simplified formulation of photocuring resin to be used as dental sealant.
      Two experimental dental sealants (CYTED1 and CYTED2) were formulated and their
      kinetic of polymerisation and physico-chemical properties were studied and
      compared to those of two commercially available sealants (Helioseal, Delton-FS).
      Rates of photoinitiated polymerisation (Rp), as well as the conversions and the
      quantum yields of polymerisation (phi(p)) were calculated. Flexural strength,
      Young's modulus, microhardness, microleakage, water sorption, and solubility were
      also tested. ANOVA, Student-Newman-Keuls, Pearson correlation and Kruskal-Wallis
      tests were used (p < 0.05). The highest Rp and phi(p) were obtained for the
      sealant CYTED2, Rp and phi(p) were similar for CYTEDl and Helioseal, and the
      lowest for Delton. Water sorption values were similar for Helioseal and CYTED2
      being higher for CYTED1 and lower for Delton. No differences were found for
      solubility and microleakage values. Mechanical properties were better for Delton
      and no differences were found within the rest of the sealants. At short
      irradiation times (30 s), the maximum effectiveness of the photoinitiating system
      was obtained by the experimental CYTED2.

PMID- 16649185
TI  - Genetic analysis of early neurogenesis: dedicated to the scientific contributions
      of Jose A. Campos-Ortega (1940-2004).
AB  - Jose Campos-Ortega stands out as one of the pioneers of developmental-genetic
      studies of early neurogenesis. He also liked to reflect about the history of
      science: how one discovery leads to the next, and what role individuals play in
      the progress of science. He had indeed started to work on a book describing the
      history of developmental genetics during the last year of his life. His goal in
      this book was to "explain how developmental genetics originated, how it
      transformed developmental biology and, while doing so, how it contributed to
      achieve the biological synthesis." In the following, I would like to reflect on
      the origin and growth of the field Campos-Ortega contributed so much. In doing
      so, it is of particular interest to consider his scientific roots, and the manner
      in which he entered the stage of developmental genetics. I believe that Campos
      Ortega's unusual scientific background influenced in an important manner the way
      in which he shaped the study of early neurogenesis.

PMID- 16649186
TI  - The efficacy and safety of rituximab in patients with active rheumatoid arthritis
      despite methotrexate treatment: results of a phase IIB randomized, double-blind,
      placebo-controlled, dose-ranging trial.
AB  - OBJECTIVE: To examine the efficacy and safety of different rituximab doses plus
      methotrexate (MTX), with or without glucocorticoids, in patients with active
      rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs
      (DMARDs), including biologic agents. METHODS: A total of 465 patients were
      randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg
      [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either
      placebo glucocorticoids, intravenous methylprednisolone premedication, or
      intravenous methylprednisolone premedication plus oral prednisone for 2 weeks.
      All patients received MTX (10-25 mg/week); no other DMARDs were permitted.
      RESULTS: Significantly more patients who received 2 500-mg or 2 1,000-mg
      infusions of rituximab met the American College of Rheumatology 20% improvement
      criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively)
      compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%,
      34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were
      achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease
      Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to
      good responses on the European League Against Rheumatism criteria (P < 0.0001)
      reflected the ACR criteria responses. Glucocorticoids did not contribute
      significantly to the primary efficacy end point, ACR20 response at 24 weeks.
      Intravenous glucocorticoid premedication reduced the frequency and intensity of
      first infusion-associated events; oral glucocorticoids conferred no additional
      safety benefit. Rituximab was well tolerated; the type and severity of infections
      was similar to those for placebo. CONCLUSION: Both rituximab doses were effective
      and well tolerated when added to MTX therapy in patients with active RA. The
      primary end point (ACR20 response) was independent of glucocorticoids, although
      intravenous glucocorticoid premedication improved tolerability during the first
      rituximab infusion.

PMID- 16649187
TI  - Cellular events leading to chondrocyte death after cartilage impact injury.
AB  - OBJECTIVE: We undertook this study to test our postulate that leukocytes extend
      the zone of injury in cartilage after acute mechanical trauma. METHODS: Fresh
      cadaveric canine femoral condyles were subjected to 20-25-MPa impact injury.
      Condyle explants or dispersed chondrocytes were cultured with autologous blood
      mononuclear leukocytes (MNLs). Viability of chondrocytes at varying distances
      from the impact site was assessed by trypan blue exclusion. RESULTS: Mechanical
      injury caused a significant loss of viable chondrocytes over 7 days, even in
      cartilage >10 mm from the impact site. After biomechanical stress, death of cells
      within 10 mm of the impact could be largely prevented by addition of N(G)
      monomethyl-L-arginine to inhibit nitric oxide (NO) generation. Chondrocytes
      within 10 mm of the impact were also susceptible to killing by living MNLs, but
      not by incubation with the supernatants of endotoxin-activated MNLs. Chondrocytes
      in this vulnerable zone expressed intercellular adhesion molecule 1 (ICAM-1)
      (CD54), facilitating attachment of MNLs that localized adjacent to the
      chondrocytes. Leukocytes killed dispersed chondrocytes harvested from the impact
      zone by generation of reactive oxygen species. Leukocyte-mediated killing could
      be blocked by desferoxamine or by antibodies to CD18, which prevent attachment of
      leukocytes to ICAM-1-expressing chondrocytes. CONCLUSION: Our data suggest that
      after mechanical injury, chondrocytes distant from the site may be killed through
      the generation of NO. Inflammatory leukocytes further extend the zone of
      chondrocyte death by adhering to chondrocytes expressing ICAM-1 and by inducing
      the accumulation of free oxygen radicals in the chondrocyte cytoplasm. Patients
      may benefit from therapies that reduce infiltration of inflammatory leukocytes
      into acutely injured cartilage.

PMID- 16649188
TI  - Evaluation of the alkaline Comet assay conducted with the wetlands plant Bacopa
      monnieri L. as a model for ecogenotoxicity assessment.
AB  - Wetlands play a key role in maintaining environmental quality, and wetlands
      plants could serve as model organisms for determining the genotoxic effects of
      pollutants contaminating these areas. In the present study, DNA damage was
      evaluated in a wetlands plant, Bacopa monnieri L., as a potential tool for the
      assessment of ecogenotoxicity. The Comet assay was used for detecting DNA damage
      in B. monnieri exposed to two model mutagens, ethyl methanesulfonate (EMS) and
      methyl methanesulfonate (MMS). Significant (P < 0.05) dose-dependent increases in
      DNA damage were observed following treatments conducted by exposing both isolated
      nuclei (acellular or in vitro exposure) and whole plants (in vivo exposure) to
      0.01-5 mM EMS and 0.05-100 microM MMS for 2 hr at (26 +/- 2) degrees C. The assay
      was then used to evaluate the genotoxic potential of cadmium (Cd), a wetlands
      contaminant. In vitro exposure of nuclei from untreated leaves to 0.001-200
      microM Cd for 2 hr resulted in significant (P < 0.05) levels of DNA damage. Cd
      concentrations >or=0.01 microM induced DNA damage as evidenced by increases in
      the Olive tail moment. In vivo exposure of plants to 0.01-500 microM Cd for 2, 4,
      and 18 hr resulted in dose- and time-dependent increases in DNA damage in the
      nuclei isolated from roots and leaves. Cd-induced DNA damage was greater in roots
      than leaves. To our knowledge, this is the first report describing the use of a
      wetlands plant for genotoxicity assessment, using the Comet assay.

PMID- 16649189
TI  - Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency
      of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous mice.
AB  - Exposure to inorganic arsenic in drinking water is linked to cancer in humans,
      but the mechanism of arsenic-induced cancer is not clear. Arsenic is not a
      powerful point mutagen, but can cause chromosome malsegregation and mitotic
      recombination, two events that can cause loss of tumor suppressor alleles and
      thereby contribute to the evolution of cancerous cells. To determine whether
      arsenic increases the frequency of allele loss due to either malsegregation or
      mitotic recombination in vivo, Aprt(+/-) hybrid mice were exposed to sodium
      arsenite (10 mg/L) in their drinking water for 10 weeks. To determine whether
      arsenic enhances the action of a known mutagen, half of the arsenic-treated mice
      were exposed to benzo[a]pyrene (BaP) for 8 weeks by skin painting (500
      nmoles/week). Cells were taken from painted dorsal skin and cultured in the
      presence of 2,6-diaminopurine (DAP), to select colonies lacking adenosine
      phosphoribosyl transferase (Aprt) activity. The frequency of DAP-resistant
      (DAP(r)) colonies varied substantially within the treatment groups, but there was
      no significant difference between the groups. Analysis of DNA from DAP(r)
      colonies suggested that mitotic recombination contributed to the loss of wild
      type Aprt allele. Whether arsenic or BaP enhanced or diminished the frequency of
      this process could not be deduced from these data.

PMID- 16649190
TI  - Comparative overview of current international strategies and guidelines for
      genetic toxicology testing for regulatory purposes.
AB  - National and international regulatory agencies historically have used
      genotoxicity information as part of a weight-of-evidence approach to evaluate
      potential human carcinogenicity. Additionally, some agencies consider heritable
      mutation a regulatory endpoint. Furthermore, genotoxicity has the potential to
      contribute to other adverse health conditions. This article provides a
      comparative overview of the testing strategies used by regulatory agencies
      throughout the world. Despite minor variations in details, the genotoxicity test
      schemes for most regulatory entities generally comprise three tests: a bacterial
      gene mutation assay, an in vitro mammalian cell assay for gene mutation and/or
      chromosome aberrations, and often an in vivo assay for chromosomal effects. In
      some cases, fewer than these three tests are required. In other cases, when
      exposure data, structure-activity considerations, or other factors warrant, even
      chemicals negative in the three baseline tests may be subject to additional
      testing. If genotoxicity is identified by the baseline screening tests,
      assessment of the ability of the chemical to interact with DNA in the gonad may
      be required. This may apply regardless of whether or not a cancer bioassay has
      been triggered. Mutagens positive in second stage gonadal assay(s) may be tested
      in third stage in vivo rodent tests to provide data for a quantitative risk
      assessment. In all testing, theutilization of internationally-recognized
      protocols, where they exist, is advisable, although not in all instances
      required. When testing for regulatory purposes, it is advisable to verify the
      testing program with the specific regulatory body or bodies responsible
      forregulatory oversight before beginning testing.

PMID- 16649191
TI  - Susceptibility of adult Coccinella septempunctata (Coleoptera: Coccinellidae) to
      insecticides with different modes of action.
AB  - Five insecticides (pyriproxifen, imidacloprid, deltamethrin + heptenophos, lambda
      cyhalothrin and Bacillus thuringiensis Berliner subsp. tenebrionis) were examined
      in the laboratory for their acute detrimental side-effects at field rates on
      adult seven-spot ladybird beetle, Coccinella septempunctata L. The toxicity of
      the preparations was determined by measuring the acute surface contact effects
      (dried spray on leaves of Philadelphus coronarius L.), except for B.
      thuringiensis where mixed pollen was treated. Four to six concentrations were
      tested (pyriproxifen 12.5, 25, 50, 100, 200, 400 mg AI litre(-1); imidacloprid
      62.4, 125, 250, 500 mg AI litre(-1); deltamethrin + heptenophos 26.4, 53.1,
      106.3, 212.5 mg AI litre(-1); lambda-cyhalothrin 1.1, 3.4, 10, 30 mg AI litre(
      1); B. thuringiensis 1.5, 3.0, 12.0, 48, 192, 768 mg AI litre(-1)), with 22
      adults exposed per concentration. All tests were conducted in the laboratory of
      the Plant Protection Department (University of Debrecen, Hungary) at 22-25
      degrees C, 40-60% RH, under a 16:8 h light:dark photoperiod in 1998-1999. Data
      were analyzed by probit analysis, probit transformation and analysis of variance.
      According to different categories of evaluation, pyriproxifen, imidacloprid and
      B. thuringiensis subsp. tenebrionis seem to be safe for C. septempunctata adults
      but the other two preparations were moderately harmful to them, which requires
      further semi-field or field tests to measure their real effect under field
      conditions.

PMID- 16649192
TI  - Delayed cuticular penetration and enhanced metabolism of deltamethrin in
      pyrethroid-resistant strains of Helicoverpa armigera from China and Pakistan.
AB  - The penetration and metabolism of [14C]deltamethrin was studied in susceptible
      and resistant Chinese and Pakistani strains of Helicoverpa armigera (Hubner),
      which were resistant to deltamethrin by 330- and 670-fold, respectively. The
      penetration of deltamethrin into resistant individuals was significantly slower
      than into susceptible individuals over a 24-h period. The time taken for 50%
      penetration of the applied deltamethrin was 1 h for the susceptible strain and 6
      h for both of the resistant strains. The internal radioactivity was reduced by
      the larvae of resistant strains much faster than by the susceptible larvae. After
      48 h, 40% of the penetrated deltamethrin was still inside the larvae of the
      susceptible strain, in comparison with 1.5-5% in the Pakistani strain and 8-14%
      in the Chinese strain. Both of the resistant strains produced methanol-soluble
      and water-soluble metabolites, but the susceptible strain produced methanol
      soluble metabolites only. By 12, 24 and 48 h after dosing, the amount of methanol
      soluble metabolites excreted by the resistant strains was almost double that of
      the susceptible strain. Both of the resistant strains also excreted 5-7% of the
      penetrated dose as a water-soluble metabolite after 48 h. In comparison with the
      Chinese strain, the Pakistani strain exhibited slower penetration, lower internal
      content and faster excretion of deltamethrin, which correlated with the higher
      resistance of the Pakistani strain. These findings show that the resistant
      Pakistani and Chinese strains of H. armigera possess mechanisms of reduced
      cuticular penetration and enhanced metabolism of deltamethrin and perhaps other
      pyrethroids.

PMID- 16649193
TI  - LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid
      arthritis.
AB  - OBJECTIVE: Human osteoclast formation from mononuclear phagocyte precursors
      involves interactions between tumor necrosis factor (TNF) ligand superfamily
      members and their receptors. LIGHT is a transmembrane protein expressed and shed
      from the surface of activated T cells. Since activated T cells have been
      implicated in osteoclastogenesis in rheumatoid arthritis (RA), this study sought
      to determine whether LIGHT can regulate RANKL/cytokine-induced osteoclast
      formation, to identify the mechanism by which LIGHT influences
      osteoclastogenesis, and to investigate the presence of LIGHT in the serum of RA
      patients. METHODS: The effect of LIGHT on human and murine osteoclast formation
      was assessed in the presence and absence of neutralizing reagents to known
      osteoclastogenic factors. Serum levels of LIGHT in RA patients were measured by
      enzyme-linked immunosorbent assay. RESULTS: In the presence and absence of RANKL,
      LIGHT induced osteoclast formation from both human peripheral blood mononuclear
      cells and murine macrophage precursors, in a dose-dependent manner, whereas no
      inhibition was observed by adding osteoprotegerin, RANK:Fc, TNFalpha, or
      interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or
      lymphotoxin beta receptor. However, formation of osteoclasts was significantly
      decreased by the soluble decoy receptor for LIGHT, DcR3, and by blocking
      antibodies to the p75 component of the TNF receptor. A significant increase in
      LIGHT levels in the serum of RA patients compared with normal controls was also
      noted. CONCLUSION: Our results indicate that LIGHT promotes RANKL-mediated
      osteoclastogenesis and that it can induce osteoclast formation by a mechanism
      independent of RANKL. The increased concentration of LIGHT in patients with RA
      raises the possibility that LIGHT may play a role in immunopathogenic conditions
      that are associated with localized or systemic bone loss.

PMID- 16649194
TI  - Restoration of shoulder function with nerve transfers in traumatic brachial
      plexus palsy patients.
AB  - Shoulder stabilization is of utmost importance in upper extremity reanimation
      following paralysis from devastating injuries. Although secondary procedures such
      as tendon and muscle transfers have been used, they never achieve a functional
      recovery comparable to that following successful reinnervation of the
      supraspinatus, deltoid, teres minor, and infraspinatus muscles. Early restoration
      of suprascapular and axillary nerve function through timely brachial plexus
      reconstruction offers a good opportunity to restore shoulder-joint stability,
      adequate shoulder abduction, and external rotation function. Overall, in our
      series, 79% of patients achieved good and excellent shoulder abduction (muscle
      grade, +3 or more), and 55% of patients achieved good or excellent shoulder
      external rotation after reinnervation of the suprascapular nerve. The best
      results were seen when direct neurotization of the suprascapular nerve from the
      distal spinal accessory nerve or neurotization by the C5 root was carried out.
      Concomitant neurotization of the axillary nerve yields improved outcomes in
      shoulder abduction and external rotation function.

PMID- 16649195
TI  - An uncommon cause of hip pain.

PMID- 16649196
TI  - Report on a multicenter fMRI quality assurance protocol.
AB  - Temporal stability during an fMRI acquisition is very important because the blood
      oxygen level-dependent (BOLD) effects of interest are only a few percent in
      magnitude. Also, studies involving the collection of groups of subjects over time
      require stable scanner performance over days, weeks, months, and even years. We
      describe a protocol designed by one of the authors that has been tested for
      several years within the context of a large, multicenter collaborative fMRI
      research project (FIRST-BIRN). A full description of the phantom, the quality
      assurance (QA) protocol, and the several calculations used to measure performance
      is provided. The results obtained with this protocol at multiple sites over time
      are presented. These data can be used as benchmarks for other centers involved in
      fMRI research. Some issues with the various protocol measures are highlighted and
      discussed, and possible protocol improvements are also suggested. Overall, we
      expect that other fMRI centers will find this approach to QA useful and this
      report may facilitate developing a similar QA protocol locally. Based on the
      findings reported herein, the authors are convinced that monitoring QA in this
      way will improve the quality of fMRI data.

PMID- 16649197
TI  - The role of fMRI in drug discovery.
AB  - Pharmacological functional (phMRI) studies are making a significant contribution
      to our understanding of drug-effects on brain systems. Pharmacological fMRI has
      an additional contribution to make in the translation of disease models and
      candidate compounds from preclinical to clinical investigation and in the early
      clinical stages of drug development. Here it can demonstrate a proof-of-concept
      of drug action in a small human cohort and thus contribute substantially to
      decision-making in drug development. We review the methods underlying
      pharmacological fMRI studies and the links that can be made between animal and
      human investigations. We discuss the potential fMRI markers of drug effect,
      experimental designs and caveats in interpreting hemodynamic fMRI data as
      reflective of changes in neuronal activity. Although there are no current
      published examples of fMRI applied to novel compounds, we illustrate the
      potential of fMRI across a range of applications and with specific reference to
      processing of pain in the human brain and pharmacological analgesia.
      Pharmacological fMRI is developing to meet the neuroscientific challenges.
      Electrophysiological methods can be used to corroborate the drug effects measured
      hemodynamically with fMRI. In future, pharmacological fMRI is likely to extend to
      examinations of the spinal cord and into pharmacogenetics to relate genetic
      polymorphisms to differential responses of the brain to drugs.

PMID- 16649198
TI  - JMRI special issue: clinical potential of brain mapping using MRI.

PMID- 16649199
TI  - Diagnostic functional MRI: illustrated clinical applications and decision-making.
AB  - Functional magnetic resonance imaging (fMRI) has become a popular research tool,
      yet its use for diagnostic purposes and actual treatment planning has remained
      less widespread. The literature yields rather sparse evidence-based data on
      clinical fMRI applications and accordant decision-making. Notwithstanding, blood
      oxygenation level dependent (BOLD)- and arterial spin labeling (ASL)-fMRI can be
      judiciously combined with perfusion measurements, electroencephalographic (EEG)
      recordings, diffusion-weighted imaging (DWI), and fiber tractographies to assist
      clinical decisions. In this article we provide an overview of clinical fMRI
      applications based on illustrative examples. Assessment of cochlear implant
      candidates by fMRI is covered in some detail, and distinct reference is made to
      particular challenges imposed by brain tumors, other space-occupying lesions,
      cortical dysplasias, seizure disorders, and vascular malformations. Specific
      strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI
      studies in individual patients are highlighted.

PMID- 16649200
TI  - Clinical applicability of functional MRI.
AB  - Functional MRI (fMRI) has become the most widely used modality for examining
      human brain function in basic and clinical neuroscience. As compared to the
      application of fMRI in basic neuroscience research, clinical fMRI presents unique
      challenges. A growing body of literature supports the feasibility of clinical
      fMRI, with the best-studied applications being localization of motor cortex and
      lateralization of language. While it may be tempting to assume that fMRI will
      supercede prior approaches, it may turn out that fMRI will be used to complement
      more difficult or invasive methods rather than replace them entirely. This
      article focuses on fMRI studies in patients and patient populations. Specific
      considerations for such applications include pathophysiological effects on
      functional physiology, brain-behavior correlations in the presence of cognitive
      or sensorimotor deficits, and test-retest reliability for longitudinal studies.

PMID- 16649201
TI  - Future prospects for fMRI in the clinic.
AB  - Functional MRI (fMRI) has tremendous clinical potential that is as yet
      unrealized. There are tremendous unmet medical needs that fMRI could address with
      significant benefit to human health. However, both medical and technical barriers
      prevent this benefit from accruing today. Technical barriers may be the reflexive
      focus of the current practitioners of fMRI, a technically savvy group. However,
      the real challenge lies in the medical realm, and this will require
      multidisciplinary and interdisciplinary work since the technical aspects of fMRI
      are ahead of the medical aspects. This can be seen in a range of diseases from
      Alzheimer's disease to schizophrenia to ischemic stroke: in each case our ability
      to image changes with fMRI outstrips our ability to do anything useful for the
      patient with them. Diagnostic imaging will always be linked in the clinic to
      therapeutic choices, and therefore the most powerful approach to link fMRI more
      directly to the clinic will be to tie fMRI to therapy development and
      implementation.

PMID- 16649202
TI  - Frontiers of brain mapping using MRI.
AB  - Over the past dozen years, the use of MRI techniques to map brain function (fMRI)
      has sparked a great deal of research. The ability of fMRI to image several
      different physiological processes concurrently (i.e., blood oxygenation, blood
      flow, metabolism) and noninvasively over large volumes make it the ideal choice
      for many different areas of neuroscience research in addition to countless
      applications in clinical settings. Furthermore, with the advent of high magnetic
      fields (and other hardware advancements, i.e., parallel imaging) for both human
      and animal research, spatial and temporal resolutions continue to be pushed to
      higher levels because of increases in the sensitivity as well as specificity of
      MR-detectable functional signals. fMRI methodology continues to grow and has the
      ability to cater to many different research applications. There seems to be no
      foreseeable end in sight to the advancement of fMRI techniques and its subsequent
      use in basic research as well as in clinical settings. In this work, fMRI
      techniques and the ongoing development of existing techniques are discussed with
      implications for the future of fMRI.

PMID- 16649203
TI  - Combining EEG and fMRI: a multimodal tool for epilepsy research.
AB  - Patients with epilepsy often present in their electroencephalogram (EEG) short
      electrical potentials (spikes or spike-wave bursts) that are not accompanied by
      clinical manifestations but are of important diagnostic significance. They result
      from a population of abnormally hyperactive and hypersynchronous neurons. It is
      not easy to determine the location of the cerebral generators and the other brain
      regions that may be involved as a result of this abnormal activity. The
      possibility to combine EEG recording with functional MRI (fMRI) scanning opens
      the opportunity to uncover the regions of the brain showing changes in the fMRI
      signal in response to epileptic spikes seen in the EEG. These regions are
      presumably involved in the abnormal neuronal activity at the origin of epileptic
      discharges. This paper reviews the methodology involved in performing such
      studies, particularly the challenge of recording a good quality EEG inside the MR
      scanner while scanning is taking place, and the methods required for the
      statistical analysis of the combined EEG and fMRI time series. We review the
      results obtained in patients with different types of epileptic disorders and
      discuss the difficult theoretical problems raised by the interpretation of an
      increase (activation) and decrease (deactivation) in blood oxygen level dependent
      (BOLD) signal, both frequently seen in response to spikes.

PMID- 16649204
TI  - Special considerations for functional magnetic resonance imaging of pediatric
      populations.
AB  - Functional MRI (fMRI) provides a noninvasive means of studying both typical and
      atypical brain development in vivo. However, the developmental and clinical
      status of the populations of interest impact how neuroimaging data should be
      collected, analyzed, and interpreted. In the present work, we review
      methodological and theoretical issues relevant to developmental and clinical
      neuroimaging research and provide possible approaches for addressing each. These
      issues include accounting for differences in biological noise, neuroanatomy,
      motion, and task performance. Finally, we emphasize the importance of a
      converging methods approach in constraining and supporting interpretations of
      pediatric imaging results.

PMID- 16649205
TI  - Role of fMRI in the decision-making process: epilepsy surgery for children.
AB  - Functional MRI (fMRI) is increasingly being used to evaluate children and
      adolescents who are candidates for surgical treatment of intractable epilepsy. It
      has the advantage of being noninvasive and well tolerated by young people. By
      identifying important functional regions within the brain, including
      unpredictable patterns of functional reorganization, it can aid in surgical
      decision-making. Here we illustrate this using a number of case studies from the
      pediatric epilepsy surgery program at our institution. We describe how fMRI, used
      in conjunction with conventional investigative methods such as neuropsychological
      assessment, MRI, and electrophysiology, can 1) help to improve functional outcome
      by enabling resective surgery that spares functional cortex, 2) guide surgical
      intervention by revealing when reorganization of function has occurred, and 3)
      show when abnormal cortex is also functionally active, and hence that surgery may
      not be the best option. Altogether, these roles have reduced the need for
      invasive procedures that can be both risky and distressing for young people with
      epilepsy. In our experience, fMRI has significantly contributed to the decision
      making process, and improved the counseling and management of young people with
      intractable epilepsy.

PMID- 16649206
TI  - Principles of magnetic resonance assessment of brain function.
AB  - MRI has advanced to being one of the major tools for the assessment of brain
      function. This review article examines the basic principles that underpin these
      measurements. The main emphasis is on the characteristics and detection of blood
      oxygen level dependent (BOLD) contrast. In the first part of the article the
      relationship between BOLD, blood flow, blood oxygen, and the rate of metabolic
      consumption of oxygen is described. The four contrast mechanisms that contribute
      to the BOLD signal change, namely extravascular static and dynamic dephasing,
      intravascular T2-like changes, and the intravascular frequency offset effect are
      described in terms of their spatial localization and relative contributions to
      the BOLD signal. The current model of changes in blood flow being an indirect
      consequence of synaptic input to a region is presented. The second section of the
      article deals with the imaging characteristics of BOLD in terms of the attainable
      spatial resolution and linear system characteristics. In the third section,
      practical BOLD imaging is examined for choice of pulse sequence, resolution, echo
      time (TE), repetition time (TR), and flip angle. The final section touches on
      other MRI approaches that are relevant to cognitive neuroimaging, in particular
      the measurement of blood flow, blood volume, resting state fluctuations in the
      BOLD signal, and measures of connectivity using diffusion tensor imaging and
      fiber-tracking.

PMID- 16649207
TI  - Role of functional imaging in neurological disorders.
AB  - Neuroimaging in recent years has greatly contributed to our understanding of a
      wide range of aspects related to central neurological diseases. These include the
      classification and localization of disease, such as in headache; the
      understanding of pathology, such as in Parkinson's disease (PD); the mechanisms
      of reorganization, such as in stroke and multiple sclerosis (MS); and the
      subclinical progress of disease, such as in amyotrophic lateral sclerosis (ALS).
      Apart from presurgical mapping, however, the clinical applications so far are
      limited. Nevertheless, functional imaging does enable the formulation of
      neurobiological hypotheses that can be tested clinically, and thus is well suited
      for testing classic clinical hypotheses about how the brain works. Understanding
      the mechanisms and sites of pathology, such as has been achieved in cluster
      headaches, facilitates the development of new therapeutic strategies.

PMID- 16649208
TI  - Design and analysis of fMRI studies with neurologically impaired patients.
AB  - Functional neuroimaging can be used to characterize two types of abnormality in
      patients with neurological deficits: abnormal functional segregation and abnormal
      functional integration. In this paper we consider the factors that influence the
      experimental design, analysis, and interpretation of such studies. With respect
      to experimental design, we emphasize that: 1) task selection is constrained to
      tasks the patient is able to perform correctly, and 2) the most sensitive designs
      entail presenting stimuli of the same type close together. In terms of data
      preprocessing, prior to statistical analysis, we note that structural pathology
      may call for constraints on nonlinear transformations, used by spatial
      normalization, to prevent distortion of intact tissue. This means that one may
      have to increase spatial smoothing to reduce the impact of inaccurate
      normalization. Important issues in statistical modeling concern the first level
      of analysis (estimation of activation within subject), which has to distinguish
      correct from incorrect responses. At the second level (between subjects),
      inference should be based on between-subjects variance. Provided that these and
      other constraints are met, deficits in functional segregation are indicated when
      activation in one or a set of regions is higher or lower in patients relative to
      control subjects. In contrast, deficits in functional integration are implied
      when the influence of one brain region on another is stronger or weaker in
      patients relative to control subjects.

PMID- 16649209
TI  - The clinical potential of functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging (fMRI) has had a huge impact on
      understanding the healthy human brain. To date it has had much less impact in
      clinical neuroscience or clinical practice. The reasons for this are in part that
      the image acquisition, paradigm design, and data analysis strategies used
      presently are not sufficiently standardized. This makes the comparison of results
      across individuals, scanning sessions, and centers difficult. Nevertheless, there
      are emerging applications for clinical fMRI, and as the field matures the number
      of applications is likely to grow. It seems certain that fMRI has an important
      role to play in helping us understand the mechanisms of neuropsychiatric diseases
      and in helping to identify effective therapeutic strategies.

PMID- 16649210
TI  - Presurgical planning for tumor resectioning.
AB  - Since the birth of functional magnetic resonance imaging (fMRI)-a noninvasive
      tool able to visualize brain function-now 15 years ago, several clinical
      applications have emerged. fMRI follows from the neurovascular coupling between
      neuronal electrical activity and cerebrovascular physiology that leads to three
      effects that can contribute to the fMRI signal: an increase in the blood flow
      velocity, in the blood volume and in the blood oxygenation level. The latter
      effect, gave the technique the name blood oxygenation level dependent (BOLD)
      fMRI. One of the major clinical uses is presurgical fMRI in patients with brain
      abnormalities. The goals of presurgical fMRI are threefold: 1) assessing the risk
      of neurological deficit that follows a surgical procedure, 2) selecting patients
      for invasive intraoperative mapping, and 3) guiding of the surgical procedure
      itself. These are reviewed here. Unfortunately, randomized trials or outcome
      studies that definitively show benefits to the final outcome of the patient when
      applying fMRI presurgically have not been performed. Therefore, fMRI has not yet
      reached the status of clinical acceptance. The final purpose of this article is
      to define a roadmap of future research and developments in order to tilt pre
      surgical fMRI to the status of clinical validity and acceptance.

PMID- 16649211
TI  - Genetic overlap between P300, P50, and duration mismatch negativity.
AB  - Mismatch Negativity (MMN), P300, and P50 suppression event-related potential
      (ERP) components measure intermediate stages of information processing but little
      is known of how they relate to each other genetically. The present study used
      multivariate genetic model fitting analytic techniques in 46 monozygotic and 32
      dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19
      channel electroencephalograph (EEG). Zygosity was determined using DNA
      genotyping. Little evidence for either genetic or environmental association
      between each of the three ERP paradigms was found. This result suggests that
      P300, MMN, and P50 suppression serve to evaluate different brain information
      processing functions that may be mediated by distinct neurobiological mechanisms
      which in turn are influenced by different sets of genes. Within paradigm, P300
      amplitude and latency shared about half of their genetic effects.

PMID- 16649212
TI  - ATP-binding to P-type ATPases as revealed by biochemical, spectroscopic, and
      crystallographic experiments.
AB  - P-type ATPases form a large family of cation translocating ATPases. Recent
      progress in crystallography yielded several high-resolution structures of Ca(2+)
      ATPase from sarco(endo)plasmic reticulum (SERCA) in various conformations. They
      could elucidate the conformational changes of the enzyme, which are necessary for
      the translocation of cations, or the mechanism that explains how the nucleotide
      binding is coupled to the cation transport. However, crystals of proteins are
      usually obtained only under conditions that significantly differ from the
      physiological ones and with ligands that are incompatible with the enzyme
      function, and both of these factors can inevitably influence the enzyme
      structure. Biochemical (such as mutagenesis, cleavage, and labeling) or
      spectroscopic experiments can yield only limited structural information, but this
      information could be considered relevant, because measurement can be performed
      under physiological conditions and with true ligands. However, interpretation of
      some biochemical or spectroscopic data could be difficult without precise
      knowledge of the structure. Thus, only a combination of both these approaches can
      extract the relevant information and identify artifacts. Briefly, there is good
      agreement between crystallographic and other experimental data concerning the
      overall shape of the molecule and the movement of cytoplasmic domains. On the
      contrary, the E1-AMPPCP crystallographic structure is, in details, in severe
      conflict with numerous spectroscopic experiments and probably does not represent
      the physiological state. Notably, the E1-ADP-AlF(4) structure is almost identical
      to the E1-AMPPCP, again suggesting that the structure is primarily determined by
      the crystal-growth conditions. The physiological relevance of the E2 and E2-P
      structures is also questionable, because the crystals were prepared in the
      presence of thapsigargin, which is known to be a very efficient inhibitor of
      SERCA. Thus, probably only crystals of E1-2Ca conformation could reflect some
      physiological state. Combination of biochemical, spectroscopic, and
      crystallographic data revealed amino acids that are responsible for the
      interaction with the nucleotide. High sequence homology of the P-type ATPases in
      the cytoplasmic domains enables prediction of the ATP-interacting amino acids
      also for other P-type ATPases.

PMID- 16649214
TI  - The extracellular matrix in oral squamous cell carcinoma: friend or foe?
AB  - Oral squamous cell carcinoma is a disfiguring, highly invasive and metastatic
      cancer. Despite advances in detection and therapy, many patients will continue to
      face a poor prognosis. It is well established that the predominate factor
      determining overall survival in patients with oral squamous cell carcinoma is
      lymph node involvement. Tumor growth and progression to invasive cancer requires
      tumor cell interactions with the extracellular matrix. An understanding of how
      the extracellular matrix influences tumor development and invasion is fundamental
      in the development of new prognostic indicators and treatment strategies for oral
      squamous cell carcinoma. In this review, we summarize how changes in the
      extracellular matrix contribute to oral cancer development.

PMID- 16649215
TI  - Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease,
      affective disorders, posttraumatic stress disorder, schizophrenia, and substance
      dependence.
AB  - Genetic variation at the locus encoding the brain derived neurotrophic factor
      (BDNF) has been implicated in some neuropsychiatric disorders such as Alzheimer's
      disease (AD), affective disorders (AFDs), schizophrenia, and substance
      dependence. We therefore performed a mutation scan of the BDNF gene to identify
      novel gene variants and examined the association between BDNF variants and
      several neuropsychiatric phenotypes in European American (EA) subjects and
      controls. Using denaturing high performance liquid chromatography (dHPLC), we
      identified a novel variant (G-712A) in the putative promoter region. This variant
      and two previously reported BDNF SNPs (C270T and Val66Met) were genotyped in 295
      patients with AD, 108 with AFDs, 96 with posttraumatic stress disorder (PTSD), 84
      with schizophrenia, 327 with alcohol and/or drug dependence, and 250 normal
      control subjects. No association was found between these three BDNF gene variants
      and AD, AFDs, PTSD, or schizophrenia. However, there was a nominally higher
      frequency of the G-712A G-allele and the G/G genotype in subjects with substance
      dependence than in controls (Allele: chi(2) = 4.080, df = 1, P = 0.043; Genotype:
      chi(2) = 7.225, df = 2, P = 0.027). Although after correction for multiple
      testing, the findings are not considered significant (threshold P-value was set
      at 0.020 by the program SNPSpD), logistic regression analyses confirmed the
      modest association between SNP G-712A and substance dependence, when the sex and
      age of subjects were taken into consideration. The negative results for AFDs,
      PTSD, and schizophrenia could be due to the low statistical power. Further study
      with larger samples is warranted.

PMID- 16649217
TI  - Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled
      analysis of 15,500 patients.
AB  - BACKGROUND: The magnitude of the survival benefit of taxanes as adjuvant
      chemotherapy for early breast cancer is still unclear. A pooled analysis of Phase
      III trials was performed to assess the advantages that adjuvant taxane
      chemotherapy has over standard chemotherapy. METHODS: All Phase III trials were
      considered eligible. A pooled analysis was accomplished and event-based relative
      risk ratios (RR) with 95% confidence intervals (95% CI) were derived. The
      significant differences in disease-free survival (DFS) and overall survival (OS)
      were explored. Magnitude outcome measures were absolute benefits and the number
      of patients needed to treat. A heterogeneity test was applied as well. A
      sensitivity analysis in 6 subpopulations was also performed. RESULTS: Nine trials
      designed to assess if paclitaxel or docetaxel improve survival (15,598 patients)
      were gathered. One of the 9 trials did not report OS results. Significant
      differences in favor of taxanes were seen in DFS in the overall (RR: 0.86; 95%
      CI, 0.81-0.90 [P<.00001]) and lymph node-positive population (RR: 0.84; 95% CI,
      0.79-0.89 [P<.0001]), and in OS in the overall (RR: 0.87; 95% CI, 0.81-0.83
      [P<.0001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.77-0.92
      [P<.0001]). The absolute benefits in DFS and OS in favor of taxanes ranged from
      3.3% to 4.6% and from 2.0% to 2.8%, respectively. CONCLUSIONS: Considering all
      the available Phase III trials, taxane-based adjuvant chemotherapy for early
      breast cancer seems to add a significant benefit in both DFS and OS over standard
      chemotherapy. The lack of significant heterogeneity in the sensitivity analysis
      underscores the homogeneous effect across all trials.

PMID- 16649218
TI  - Quality of life in long-term survivors of bladder cancer.
AB  - BACKGROUND: The quality of life (QOL) of long-term survivors of bladder cancer in
      a population-based registry was assessed. METHODS: The Functional Assessment of
      Cancer Therapy (FACT-BL) instrument was used to evaluate QOL in a population
      based sample of bladder cancer patients. QOL scores were compared between those
      undergoing radical cystectomy (RC) or those with an intact bladder (BI) and
      between continent and conduit urinary diversion groups. The influence of current
      age and time since diagnosis of cancer on QOL were also examined. Multivariate
      regression analyses were performed to examine the influence of age, time since
      diagnosis, current condition, treatment, stage of cancer, and comorbid conditions
      on QOL. RESULTS: A total of 259 patients participated in the study who had
      undergone RC (n=82) or other therapy (BI) (n=177). There were no differences in
      general QOL scores between RC and BI groups and between the 2 urinary diversion
      groups, but patients undergoing RC had worse sexual function scores. QOL scores
      for BI patients tended to decrease with increasing age (P=.01). Presence of
      comorbid conditions lowered QOL (P<.05). CONCLUSIONS: General QOL does not vary
      among long-term bladder cancer survivors regardless of treatment, but sexual
      functioning can be adversely affected in those undergoing cystectomy. Long-term
      QOL declines even in those with intact bladders, particularly in those with
      comorbidities.

PMID- 16649219
TI  - Phase I/II study of a combined gemcitabine, etoposide, and cisplatin chemotherapy
      regimen for metastatic urothelial carcinoma.
AB  - BACKGROUND: The authors attempted to determine the maximum tolerated dose (MTD)
      of gemcitabine in combination with etoposide and cisplatin as a chemotherapy
      regimen and investigated the safety and antitumor activity with the recommended
      doses of gemcitabine with etoposide and cisplatin for patients with metastatic
      urothelial carcinoma. METHODS: Patients age 75 years or younger with measurable
      lesions, creatinine clearance>or=50 mL per minute, and adequate bone marrow and
      hepatic function were studied. Etoposide and cisplatin were given on Days 1
      through 3 at fixed doses of 75 mg/m2 and 25 mg/m2, respectively, and gemcitabine
      was given on Days 1, 8, and 15. In the Phase I component, gemcitabine was
      administered at increasing doses from 600 mg/m2. Cycles were repeated every 28
      days unless progressive disease was encountered. RESULTS: In Phase I, with the
      initially fixed doses of etoposide and cisplatin, the MTD of gemcitabine could
      not be determined because of the occurrence of dose-limiting toxicity at Level 1
      in all 3 patients. When the doses of etoposide and cisplatin were modified to 60
      mg/m2 and 20 mg/m2, respectively, the MTD of gemcitabine was 1000 mg/m2. Next, 19
      additional patients were entered into Phase II with the recommended gemcitabine
      dose of 800 mg/m2, and 20 patients in all were treated at this dose level. The
      main toxicity was bone marrow suppression, with Grade 3 or 4 neutropenia and
      thrombocytopenia recognized in 20 patients (100%) and 14 patients (70%),
      respectively, although no toxic deaths occurred. In total, all 31 patients at all
      dose levels had an assessable response, with 6 complete responses and 15 partial
      responses observed, for an overall response rate of 67.7%. Patients who had
      visceral metastasis had a significantly worse response rate than patients who had
      lymph node metastasis alone (50.0% vs. 78.9%; P=.042). The response rate (66.7%)
      for 21 patients who received prior chemotherapy was not different from that for
      10 chemotherapy-naive patients. The median survival for all patients was 13.1
      months, and 4 patients survived for >2 years with no evidence of disease.
      Patients younger than age 65 years had significantly better survival than
      patients age 65 years or older (P=.026). CONCLUSIONS: Although bone marrow
      toxicity was considerable, combination chemotherapy with gemcitabine, etoposide,
      and cisplatin appeared to be very active in patients with urothelial carcinoma
      and may be especially promising for younger patients, although further study is
      warranted.

PMID- 16649220
TI  - High-risk cutaneous squamous cell carcinoma of the head and neck: results from
      266 treated patients with metastatic lymph node disease.
AB  - BACKGROUND: Most patients with cutaneous squamous cell carcinoma (cSCC) of the
      head and neck (HN) are at low-risk (<5%) of developing metastatic SCC to regional
      lymph nodes. However, patients with unfavorable clinicopathologic factors often
      are under appreciated by clinicians but remain at higher risk for developing
      metastatic lymph node disease and dying. METHODS: Patients were identified who
      had metastatic cSCC to lymph nodes (parotid and cervical) of the HN and who were
      treated within the context of a multidisciplinary HN cancer service between 1980
      and 2005 at Westmead Hospital (Sydney, Australia). Relevant patient details and
      data from primary lesions were analyzed and reported. RESULTS: In total, 266
      patients were treated with curative intent. The median patient age was 69 years
      among 219 males and 47 females. The majority of metastatic lymph nodes (162 of
      266 lymph nodes; 61%) were located in the parotid with or without cervical lymph
      node involvement. The median tumor thickness was 6 mm (range, 0.5-28 mm), and the
      median tumor size was 15 mm (range, 3-70 mm). Most tumors (65%) that measured
      >or=5 mm in thickness, and 30% of patients had lesions that measured >or=2 cm in
      greatest dimension. Recurrent cSCC was present in 15% of patients, and most
      lesions were located within the lymphatic drainage of the parotid on the
      temple/forehead (28%), on or around the ear (20%), or on the cheek (12%). Forty
      six percent of patients had moderately or poorly differentiated cSCC, and 5% of
      patients were immunosuppressed. A minority of patients (27%) did not have an
      identifiable index lesion. CONCLUSIONS: Data from this large, prospective data
      base, in concordance with other series, suggested that a patient with thick cSCC
      (>4-5 mm) located in proximity to the parotid gland can be considered at high
      risk. Increasing lesion size and recurrence contribute to this risk.

PMID- 16649221
TI  - Cancer-specific survival and predictors of prostate-specific antigen recurrence
      and survival in patients with seminal vesicle invasion after radical
      prostatectomy.
AB  - BACKGROUND: The objectives of the current study were to determine the long-term
      biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men
      with seminal vesicle invasion (SVI) and to identify risk factors for freedom from
      BCR and CSS in patients who received treatment in the prostate-specific antigen
      era and who had SVI identified at the time of radical prostatectomy (RP).
      METHODS: Prospective clinical, pathologic, and outcome data were collected for
      5377 men who underwent RP between June 1983 and August 2004. There were 936
      patients who were excluded because they received treatment before RP.
      Multivariable analysis was used to identify the factors that predicted BCR and
      CSS. RESULTS: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91
      of those 387 patients (24%) had lymph node involvement (LNI). In total, 210
      patients experienced BCR. For patients without LNI, the 10-year and 15-year
      freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS
      rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10
      year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10
      years, patients with LNI were 3 times more likely to die from cancer than from
      other causes; nonetheless, 66% of patients were alive despite their advanced
      stage. The preoperative prostate-specific antigen level, extracapsular extension,
      LNI, and Gleason grade were associated independently with BCR. Gleason scores of
      8 to 10 and LNI were significant predictors of CSS. CONCLUSIONS: SVI does not
      invariably signal BCR or death from cancer in patients who undergo RP and pelvic
      lymph node dissection. Fifteen years later, approximately 33% of men with SVI and
      negative lymph nodes are expected remain free of BCR, and CSS was surprisingly
      good.

PMID- 16649222
TI  - A cautionary note on the use of simulation procedures for analyzing contingency
      tables containing small expected cell frequencies.
AB  - A comparison of a simple simulation procedure and exact tests for tables used in
      psychiatric genetic studies is performed, with focus on tables with small
      expected cell counts. The study shows that naive simulation procedures using
      uniform random numbers, could lead to conservative results, as compared with
      Fisher exact test for contingency tables, thus discarding as non-significant
      tables that are significant according to the exact test. Exact tests are
      recommended as an alternative to naive simulation for evaluating the statistical
      significance of contingency tables with small expected cell counts.

PMID- 16649223
TI  - Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with
      chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma.
AB  - BACKGROUND: The combination of fludarabine, cyclophosphamide, and rituximab (FC
      R) shows significant in vitro synergism and may improve patient outcome with
      little overlapping toxicity. METHODS: Between December 2000 and June 2005, 77
      patients completed therapy after a median of 4 cycles of FC-R (fludarabine at a
      dose of 25 mg/m2 intravenously [i.v.] on Days 1-3, cyclophosphamide at a dose of
      250 mg/m2 i.v. on Days 1-3, and rituximab at a dose of 375 mg/m2 on Day 1). The
      median age of the patients was 59 years, 65% were male; 31% had previously
      untreated disease; and 44% had chronic lymphocytic leukemia (CLL), 29% had
      follicular lymphoma, and 27% other indolent lymphoid malignancies. In addition to
      standard disease response criteria, patients underwent evaluation using flow
      cytometric and/or molecular studies. RESULTS: Objective responses (OR) and
      complete responses (CR) were observed in 83% and 42%, respectively, of evaluable
      patients (n=76), respectively. For patients with CLL, the respective OR and CR
      rates were 100% and 67% as firstline therapy, and 95% and 14% as salvage therapy.
      For patients with follicular lymphoma, the respective OR and CR rates were 100%
      and 86% as firstline therapy, and 87% and 67% as salvage therapy. Responders who
      had no detectable disease on flow cytometric and/or molecular studies experienced
      prolonged remissions with no recurrences reported at a median 25 months of follow
      up. Peripheral stem cell collection using stem cell factor plus granulocyte
      colony-stimulating factor was successful in 10 of 13 patients who underwent
      mobilization (77%). CONCLUSIONS: FC-R is highly active as initial or salvage
      therapy in patients with CLL or indolent non-Hodgkin lymphoma. Collection of
      autologous stem cells during molecular remission is feasible and may facilitate
      future exploration of high-dose therapy in these patients.

PMID- 16649224
TI  - Xeroderma pigmentosum group D haplotype predicts for response, survival, and
      toxicity after platinum-based chemotherapy in advanced nonsmall cell lung cancer.
AB  - BACKGROUND: The treatment of lung cancer has reached a therapeutic plateau.
      Several mechanisms of platinum resistance have been described, including the
      removal of platinum-DNA adduct by nucleotide excision repair (NER). Polymorphisms
      within the Xeroderma pigmentosum Group D protein (XPD), a member of the NER
      pathway, are associated with alterations in enzyme activity and may change
      sensitivity to platinum-based chemotherapy. The authors investigated the relation
      between XPD polymorphisms and treatment response, toxicity, and overall survival
      in patients who received platinum-based chemotherapy for advanced nonsmall cell
      lung cancer (NSCLC). METHODS: Between 2001 and 2002, 108 patients with
      chemotherapy-naive, advanced NSCLC were recruited. Associations between
      XPD312/751 polymorphisms and XPD haplotype and treatment response, toxicity. and
      survival were evaluated. RESULTS: Significant correlations were observed between
      XPD haplotype and Grade 4 neutropenia and overall survival together with a
      greater response to platinum-based chemotherapy for the XPD *A haplotype.
      CONCLUSIONS: The XPD haplotype may represent a useful pharmacogenomic marker of
      platinum-based chemotherapy in patients with advanced NSCLC and requires
      prospective validation.

PMID- 16649225
TI  - Sequential gene expression changes in cancer cell lines after treatment with the
      demethylation agent 5-Aza-2'-deoxycytidine.
AB  - BACKGROUND: 5-Aza-2'-deoxycytidine (5-AzaC) is known well for its demethylation
      effect and is a promising anticancer agent. However, to the authors' knowledge,
      serial changes in gene expression over time after 5-AzaC treatment have not been
      studied to date. To clarify the categories of genes that are up-regulated or down
      regulated after 5-AzaC treatment, the authors surveyed the genes that had
      expression levels changed by 5-AzaC treatment in 6 hepatoma cell lines (Hep3B,
      HLE, Huh7, HepG2, PLC/PRF/5, and Huh6). METHODS: Cell lines were grown in medium
      that contained 1 microM of 5-AzaC. Changes in messenger RNA levels were monitored
      from 24 hours up to 120 hours after 5-AzaC treatment using an in-house microarray
      that consisted of 4608 combinational DNAs. Using clustering analysis to identify
      the genes that had gradually changed expression levels and to exclude the
      substantial experimental noise by microarray analysis, the authors focused on 206
      up-regulated genes and 248 down-regulated genes. RESULTS: According to their
      functional characterization, genes that were involved in the cytoskeleton and the
      extracellular matrix were enriched significantly in the up-regulated genes.
      Conversely, genes that were involved in metabolism were enriched significantly in
      the down-regulated genes. CONCLUSIONS: The current results demonstrated that 5
      AzaC can regulate the expression of groups of genes with characteristic
      functions.

PMID- 16649227
TI  - Detection of malignant hematopoietic cells in cerebral spinal fluid previously
      diagnosed as atypical or suspicious.
AB  - BACKGROUND: Involvement of the cerebrospinal fluid (CSF) by hematopoietic
      malignancies may be difficult to document by morphology alone. In cases with low
      numbers of cells or ambiguous morphology, the diagnoses of "atypical" or
      "suspicious" may be used. The significance of these diagnostic terms in this
      scenario has not been well established. METHODS: Between January 2000 and July
      2004, 32 patients with known lymphoma or leukemia and an initial diagnosis of
      "atypical" or "suspicious" using morphologic criteria were identified. Subsequent
      flow cytometry (FC) and cytologic data from these patients were evaluated.
      RESULTS: Of the 32 patients with an initial diagnosis of "atypical" or
      "suspicious," 40.6% (n = 13) had negative first and subsequent FC and morphologic
      evaluation of their CSF samples with follow-up up to 1 year. Nineteen patients
      (59.4%) had malignant hematopoietic cells identified in subsequent CSF samples by
      cytology and/or FC. CONCLUSIONS: In patients with a previous history of lymphoma
      or a hematopoietic malignancy, a majority of the patients (59.4%) with an
      "atypical" or "suspicious" diagnosis on CSF will ultimately have malignant cells
      identified in the CSF by cytology and/or FC. Many of these patients can be
      identified more expediently with the concurrent utilization of flow cytometry.

PMID- 16649228
TI  - Extracellular matrix scaffolds are repopulated by bone marrow-derived cells in a
      mouse model of achilles tendon reconstruction.
AB  - The extracellular matrix derived from porcine small intestinal submucosa (SIS
      ECM), an FDA-approved material currently used clinically for rotator cuff repair,
      has been shown to attract bone marrow-derived cells during in vivo remodeling of
      a subcutaneous implant and produce chemoattractant peptides following chemical
      degradation in vitro. The purpose of the present study was to determine if bone
      marrow-derived cells participate in the long-term remodeling of the Achilles
      tendon in a mouse model when repaired with SIS-ECM. A 2-mm gap was produced in
      the Achilles tendon of 40 chimeric mice produced to express green fluorescent
      protein (GFP) in all of their bone marrow-derived cells. Tendons were repaired by
      replacing the resected section with autologous tendon tissue or with a single
      layer sheet of lyophilized SIS-ECM. Four animals from each treatment group were
      sacrificed at 1, 2, 4, 8, and 16 weeks, and sections were harvested for
      histologic and fluorescence microscopy. Both groups showed accumulation of GFP
      expressing marrow-derived cells at the site of tendon remodeling at 1 and 2 weeks
      that were associated with areas of angiogenesis and inflammation. By 16 weeks,
      the SIS-ECM-treated group showed GFP expressing cells throughout the remodeled
      tendon in the absence of any inflammatory response, while the autologous tendon
      repair group showed no GFP expressing cells within the tendon except for
      occasional cells in the lumen of blood vessels. An SIS-ECM scaffold used for
      tendon repair recruits a population of bone marrow-derived cells that
      participates in the long-term remodeling process. The ability of SIS-ECM to
      recruit a population of marrow-derived cells to the remodeling site may alter the
      default mechanism of tendon healing. The involvement of these cells in the
      remodeling process may explain in part the process of site specific constructive
      remodeling as opposed to scar tissue formation when the ECM is used as a biologic
      scaffold for tendon reconstruction.

PMID- 16649229
TI  - Bifurcation stenting with drug eluting stents: illustration of the crush
      technique.
AB  - A number of percutaneous stenting techniques have been proposed for optimal
      treatment of bifurcation lesions. However, to date the most favorable
      interventional approach still remains controversial, since bifurcation lesions
      are associated with high procedural complication and restenosis rates. In the era
      of drug-eluting stents, crush stenting technique simplified the procedure,
      concurrently allowing full lesion coverage. The purpose of the present report is
      to review three cases treated with crush stenting and to describe in detail the
      technique and its variations.

PMID- 16649230
TI  - Cardiac events after low osmolar ionic or isosmolar nonionic contrast media
      utilization in the current era of coronary angioplasty.
AB  - OBJECTIVES: Our study aimed to compare the isosmolar nonionic dimer iodixanol and
      the low osmolar ionic agent ioxaglate in the current era of percutaneous coronary
      intervention (PCI), using clopidogrel, enoxaparine, direct stenting, and drug
      eluting stent. BACKGROUND: Previous studies have suggested an association between
      thrombus-related events and type of contrast media. METHODS: Our prospective
      single-center study included 498 consecutive patients who were assigned to
      receive either iodixanol (n = 231) or ioxaglate (n = 267). The primary endpoint
      was the cumulative rate of in-hospital major adverse clinical events (MACE). A
      secondary endpoint was the rate of angiographic or procedural complications.
      RESULTS: Clinical and angiographic baseline characteristics and procedural data
      were similar in the 2 groups. A peak anti-Xa > 0.5 IU/ml was obtained in 97% in
      both groups. Glycoprotein IIb/IIIa inhibitors were used in 42% of patients.
      Coronary stenting was performed in 91% of patients, with direct stenting in 70%,
      and drug-eluting stent in 28% of patients. In-hospital MACE was more frequent in
      patients receiving iodixanol compared with those receiving ioxaglate (4.8% vs.
      0.3%, P < 0.005). This difference was mainly related to the appearance of a large
      thrombus during PCI (6% with iodixanol vs. 0.3% with ioxaglate, P < 0.0001). In
      multivariate analysis, independent predictors of in-hospital MACE were use of
      iodixanol (P < 0.01), the higher number of stent used (P < 0.008),
      bifurcation/ostial lesion (P < 0.01), and balloon dilation before stenting (p <
      0.001). CONCLUSIONS: In our study reflecting the current era of PCI, thrombus
      related events are more frequent with the isosmolar nonionic dimer iodixanol than
      with the low osmolar ionic agent ioxaglate.

PMID- 16649231
TI  - Hyperoxemic perfusion of the left anterior descending coronary artery after
      primary angioplasty in anterior ST-elevation myocardial infarction.
AB  - OBJECTIVES: To assess left ventricle function recovery, ST-segment changes, and
      enzyme kinetic in ST-elevation myocardial infarction patients treated with
      intracoronary hyperoxemic perfusion (IHP) after primary percutaneous coronary
      intervention and compare them with the results obtained in control patients.
      BACKGROUND: IHP has been shown to attenuate microvascular reperfusion injury,
      which may result in poor LV function recovery despite successful primary
      percutaneous coronary intervention. METHODS: Twenty seven anterior ST-elevation
      myocardial infarction patients treated < or = 12 hr after symptom onset by
      primary percutaneous coronary intervention were subjected to selective IHP into
      the left anterior descending coronary artery for 90 min. They were compared with
      24 anterior ST-elevation myocardial infarction control patients matched in
      clinical and angiographic characteristics and treated with conventional primary
      percutaneous coronary intervention. Left ventricular function recovery was
      evaluated by serial 2D contrast echocardiography. RESULTS: Left anterior
      descending coronary artery recanalization was successful in all patients. After
      IHP (100% successful, duration 90 +/- 5.4 min), patients showed a 4.8 +/- 2.2 hr
      shorter time-to-peak creatine kinase release (P = 0.001), a shorter creatine
      kinase half-life period (23.4 +/- 8.9 hr vs. 30.5 +/- 5.8 hr, P = 0.006), and a
      higher rate of complete ST-segment resolution (78% vs. 42%, P = 0.01). A
      significant improvement of mean left ventricular ejection fraction (from (44 +/-
      9)% to (55 +/- 11)%, P < 0.001) and wall motion score index (from 1.77 +/- 0.2 to
      1.39 +/- 0.4, P < 0.001) was observed at 3 months in IHP patients only.
      CONCLUSION: After successful primary coronary intervention, IHP is associated
      with significant left ventricular function recovery when compared to conventional
      treatment. Enzyme kinetic and ST-segment changes suggest faster and more complete
      microvascular reperfusion and may explain the salutary effects of this new
      therapy on left ventricular function.

PMID- 16649232
TI  - Influence of plaque calcium on neointimal hyperplasia following bare metal and
      drug-eluting stent implantation.
AB  - OBJECTIVES: To examine the influence of vessel wall calcium on neointimal
      hyperplasia (NIH) following bare metal stent (BMS) and drug-eluting stent (DES)
      implantation. BACKGROUND: While procedural complications with coronary stenting
      in calcified lesions are well reported, little is known about subsequent NIH on
      plaque calcium following either BMS or DES implantation. METHODS: In the Study to
      COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial, 6 months
      follow-up volumetric intravascular ultrasound data were available for 41 lesions
      (BMS, 19; DES, 22). NIH thicknesses on superficial, deep, and noncalcified plaque
      were calculated at every 0.5 mm intervals over the stented segment. Calcified and
      less-calcified cross-sections were defined as those containing arcs of plaque
      calcium > or = 90 degrees and < 90 degrees , respectively. RESULTS: In BMS, mean
      NIH thickness on both superficial (0.24 +/- 0.23 mm) and deep calcium (0.25 +/-
      0.21 mm) was significantly smaller than that of noncalcified plaque (0.31 +/-
      0.22 mm) (P < 0.0005). NIH area was significantly smaller in calcified cross
      sections compared to less-calcified cross-sections (2.1 +/- 1.2 mm2 vs. 3.1 +/-
      1.9 mm2, P < 0.0001). While in contrast, in DES, mean NIH thickness was similar,
      irrespective of the presence or location of calcium (0.03 +/- 0.05 mm vs. 0.03 +/
      0.06 mm vs. 0.03 +/- 0.05 mm, superficial vs. deep vs. noncalcified plaque, P =
      NS). NIH area was also similar between calcified and less-calcified cross
      sections (0.3 +/- 0.6 mm2 vs. 0.3 +/- 0.6 mm2, P = NS). CONCLUSIONS: These
      results suggest that while plaque calcium may influence NIH following BMS
      implantation, NIH suppression using DES does not appear to be affected by the
      presence or location of calcium.

PMID- 16649233
TI  - Failure of transradial approach during coronary interventions: anatomic
      considerations.
AB  - The anatomy of the radial artery has yet to be systematically studied from the
      perspective of using it as a route for catheter access. We prospectively
      performed angiography of the arteries of the upper limb to delineate the anatomic
      features of the radial artery as a way to determine the feasibility of using it
      as a route for coronary intervention. We studied 2,211 consecutive patients
      submitted to transradial cardiac catheterization. In all patients, an angiography
      of the upper limb arteries was performed before and after procedure. Radial
      puncture was successful in 98.9% of patients. At angiography, anatomic variations
      of upper limb arteries were noted in 505 patients (22.8%) and included tortuous
      configurations (3.8%), stenosis (1.7%), hypoplasias (7.7%), radioulnar loop
      (0.8%), abnormal origin of the radial artery (8.3%), and lusoria subclavian
      artery (0.45%). Overall procedural success by transradial approach was 97.5%.
      Patients with anatomic variations of radial artery had a significantly lower
      puncture (96.2% vs 99.7%, P < 0.0001) and procedural (93.1% vs 98.8%, P < 0.0001)
      success. The procedure was successfully performed by radial approach in 98.8% of
      patients with tortuous configurations, 91.9% of radial stenosis, 93.9% of
      hypoplastic radial artery, 83.3% of radioulnar loop, 96.7% of radial axillary
      origin, and 60% of lusoria subclavian artery setting. Anatomic variations of the
      radial artery are not rare. However, they do not represent an important
      limitation in transradial approach if they are well documented previously.

PMID- 16649234
TI  - Late complete atriovenous block after percutaneous closure of a perimembranous
      ventricular septal defect.
AB  - Percutaneous closure of a perimembranous ventricular septal defect (VSD) is an
      alternative to surgical closure. Complications include arrhythmias and in
      particular early postoperative complete atrioventricular (AV) block. We report
      the cases of two patients, aged 2.5 and 4 years, treated with an eccentric VSD
      occluder device whom developed complete AV block 4 and 12 months after the
      procedure. The first patient experienced syncope, while the second one was
      completely asymptomatic. Both subjects underwent endocardial ventricular
      pacemaker implantation.

PMID- 16649235
TI  - Transcatheter closure of pulmonary arteriovenous malformations with amplatzer
      devices.
AB  - OBJECTIVE: To review the authors' experience with transcatheter closure of
      pulmonary arteriovenous malformations (PAVMs) using amplatzer duct occluder (ADO)
      devices and vascular plugs (AGA Medical, Golden Valley, MN) and present a novel
      technique for delivery sheath placement and device delivery. BACKGROUND: PAVMs
      can cause cyanosis, fatigue, polycythemia, and thromboembolic phenomena.
      Transcatheter closure using coils, detachable balloons, and various devices has
      replaced surgery as the preferred therapy. METHODS: Between January 2001 and
      December 2004, five patients (2M, 3F) of median age 33 years (14-49) were
      referred for transcatheter closure of multiple PAVMs. All patients were diagnosed
      previously with hereditary hemorrhagic telangectasia. The procedures were
      performed with sedation using a percutaneous transcatheter technique via the
      femoral vein under fluoroscopic guidance. RESULTS: A total of 14 PAVMs (11 ADO
      and 3 plugs) were closed in five patients. Three patients required two procedures
      after developing additional PAVMs. All attempts at PAVM closure were successful.
      Oxygen saturation increased from 88.4 +/- 6.1 to 96.4 +/- 0.5 (P < 0.05). No
      complications, including air or thromboembolism, hemoptysis, or chest pain,
      occurred. At median follow-up of 3.4 years (1.4-3.6), all patients are alive and
      have suffered no embolic phenomena or infection. CONCLUSION: Amplatzer patent
      ductus arteriosus occluders and vascular plugs are safe and effective in the
      closure of PAVMs in the acute setting and at intermediate follow-up. Placement of
      a long delivery sheath can be facilitated by the methods outlined. Though
      promising, further clinical evaluation of these devices is required. Their
      apparent advantages must be compared to other techniques and devices for
      transcatheter PAVM closure.

PMID- 16649236
TI  - A dual wire approach to severe ostial bifurcating renal artery stenosis.
AB  - Percutaneous intervention with balloon expandable stents has proven to be an
      effective measure to enhance renal blood flow and control blood pressure in
      subjects with severe ostial renal artery lesions. A small cohort of these
      subjects have an ostial bifurcation, which complicates the approach to
      revascularization. In these cases there is a concern of creating a total side
      branch occlusion during balloon expansion. We report two cases of an ostial
      lesion at a renal artery bifurcation revascularized by employing a sequential
      dilatation double guidewire technique. Using a single 7F sheath in each case,
      both renal artery branches were wired, and each branch was predilated and stented
      in a sequential fashion. Excellent angiographic results were obtained in both
      cases.

PMID- 16649237
TI  - Catheterization in neonates with pulmonary atresia with intact ventricular
      septum.
AB  - Cardiac catheterization is infrequently required in babies with pulmonary atresia
      with intact ventricular septum. The main indications are to decide on the best
      form of treatment, the options being determined by the right ventricular as well
      as infundibular morphology and the presence of right-ventricle dependent coronary
      circulation. In most cases, an interventional approach is appropriate. This can
      consist of radiofrequency or laser perforation of the atretic pulmonary valve,
      combined with balloon dilation. In some patients, additional stenting of the
      arterial duct may be needed.

PMID- 16649238
TI  - Occlusion of a large coronary-cameral fistula using the Amplatzer vascular plug
      in a 2-year old.
AB  - A 2-year-old girl underwent transcatheter occlusion of a fistula. The fistula
      originated from the right coronary artery and drained into the right atrium.
      Three interlocking Gianturco coils were initially placed in the distal portion of
      the fistula resulting in near-total occlusion of blood flow. Placing a 12-mm
      Amplatzer vascular plug obliterated the proximal, dilated portion of the fistula.
      Complete occlusion with accurate placement was achieved. Advantages and technical
      implications of the Amplatzer vascular plug in this clinical setting are
      discussed.

PMID- 16649239
TI  - Development of a novel catheter preventing the outflow of debris and thrombus on
      percutaneous transluminal angioplasty for hemodialysis access fistulas.
AB  - If a large amount of debris or thrombus dislodges from a lesion because of
      dilation of the stenotic or occluded lesion in the hemodialysis access fistula
      when angioplasty is performed, it may move into the pulmonary artery via the
      central vein, resulting in pulmonary embolism. A novel sheath has been developed
      to prevent the outflow of debris or thrombus to the central vein. The catheter
      consists of a 5 F sheath introducer and a silicone balloon attached at the tip of
      the sheath. The silicon balloon is inflated via small inflation lumen on the
      shaft wall of the sheath. In the case of percutaneous transluminal angioplasty
      (PTA), the silicone balloon is inflated to block the blood flow by a mixture of
      contrast medium and physiological saline, and then dilate a stenotic or occluded
      lesion by PTA balloon. Next, the debris and thrombus are aspirated using the
      flush-lumen of this device. Finally, the silicone balloon is deflated and the
      dilation of the lesion is confirmed. A case of hemodialysis access fistula graft
      with massive thrombotic occlusion was presented. This device enabled Fogarty
      procedure using PTA balloon and the blood flow of the graft was completely
      improved and a large amount of thrombus was removed. This novel device is useful
      to prevent the embolic complication of the intervention for hemodialysis access
      fistula.

PMID- 16649240
TI  - Feasibility and safety of transbrachial approach for patients with severe carotid
      artery stenosis undergoing stenting.
AB  - Although sporadic successful cases using the transradial approach (TRA) for
      carotid stenting have been reported, the safety and feasibility of carotid
      stenting using either TRA or a transbrachial approach (TBA) have not been fully
      investigated. Recently, we have developed a safe and feasible method of TRA for
      cerebrovascular angiographic studies. This study investigated whether a TBA
      approach using a 7-French (F) Kimny guiding catheter for carotid stenting is safe
      and feasible for patients with severe carotid stenosis. Thirteen patients were
      enrolled into this study (age range, 63-78 years). Seven of these 13 patients had
      severe peripheral vascular disease. A retrograde-engagement technique, involving
      looping 6-F Kimny guiding catheter, was utilized for carotid angiographic study.
      For carotid stenting, the 6-F Kimny guiding catheter was replaced with a 7-F
      Kimny guiding catheter, and the procedure was performed as the follows. First, an
      extra-support wire was inserted into the middle portion of external carotid
      artery (ECA). Second, a 0.035-inch Teflon wire was advanced into the common
      carotid artery. Then, the 6-F guiding catheter was exchanged for a 7-F Kimny
      guiding catheter. Third, if the first and second steps did not provide adequate
      support for exchanging the guiding catheter, a PercuSurge GuardWire was inserted
      into the ECA, followed by distal balloon inflation for an anchoring support.
      FilterWire EX was used in 9 patients and PercuSurge GuardWire in 4 patients to
      protect from distal embolization during the procedure. The procedure was
      successful in all patients. No neurological or vascular bleeding complications
      were observed and all patients were discharged uneventfully. The TBA for carotid
      stenting was safe and effective, providing a last resort for patients unsuited to
      femoral arterial access and surgical intervention.

PMID- 16649241
TI  - Perforation complicating carotid artery stenting: the use of a covered stent.
AB  - Carotid artery angioplasty and stenting has emerged as an effective strategy for
      the treatment of significant carotid artery stenosis. Perforation during carotid
      artery stenting is a very rare potential complication of the procedure. We
      describe a case of carotid artery perforation that occurred during postdilation
      of the carotid artery stent. In our case this potentially serious complication
      was successfully treated with a covered stent-graft.

PMID- 16649242
TI  - Successful percutaneous closure of paraprosthetic aorto-right ventricular leak
      using the Amplatzer duct occluder.
AB  - A 55-year-old male with persisting aorto-right ventricular paraprosthetic leak
      after mitroaortic valve replacement was hospitalized for recurrent heart failure.
      Depressed left ventricular ejection fraction and severe pulmonary hypertension
      with increased right and left ventricular filling pressures were associated with
      significant left to right shunting through the leak. Elective closure of the leak
      was obtained with a 6-4 mm Amplatzer duct occluder. No complications were
      observed, and the patient experienced complete resolution of heart failure
      symptoms, with NYHA class I heart failure 12 months after discharge.

PMID- 16649244
TI  - Novel stent system for bifurcation lesions: examination by intravascular
      ultrasound.
AB  - Bifurcation disease represents a mechanical and biological challenge for
      definitive interventional treatment. This case report discusses an experience
      with a novel stent system designed for the treatment of bifurcation lesions.

PMID- 16649245
TI  - Successful utilization of a novel aspiration thrombectomy catheter (Pronto) for
      the treatment of patients with stent thrombosis.
AB  - Stent thrombosis is a rare but catastrophic complication of percutaneous coronary
      intervention (PCI). Thrombolytic therapy is ineffective for the treatment of
      patients with stent thrombosis, while primary PCI in such patients is limited by
      a high thrombus burden in the culprit vessel often leading to distal embolization
      and extensive tissue infarction. We present three patients with stent thrombosis
      successfully treated with the adjunctive use of a novel and new aspiration
      thrombectomy device (Pronto).

PMID- 16649246
TI  - Novel double catheter technique in complex percutaneous coronary interventions.
AB  - We present a novel double catheter technique for successful complex intervention
      of a very old proximal left circumflex chronic total occlusion (>10 years old).
      Prior attempts of guide wire passage using bare wire alone, over-the wire balloon
      or microcatheter support techniques were unsuccessful.

PMID- 16649247
TI  - Extreme coronary guide catheter support: report of two cases of a novel
      telescopic guide catheter system.
AB  - Extra support of the guiding catheter is required in selected cases of
      percutaneous coronary intervention (PCI). We describe two successful cases of PCI
      of very calcified and tortuous right coronary arteries in which a novel
      telescopic guide system was devised. The system utilizes a long sheath that
      "armors" the guide catheter. The operator can adjust the support of the guiding
      system from soft up to extremely stiff.

PMID- 16649248
TI  - Use of a branch wire to anchor stents for exact placement proximal to bifurcation
      stents: the reverse Szabo technique.
AB  - This report describes a technique for correct positioning of a stent proximal to
      a bifurcation lesion treated with V-stents. A second wire passed through the
      first cell of a stent, the opposite end of the anchor wire technique as first
      described by Szabo et al, facilitated precise stent placement and eliminated
      erroneous positioning inside or outside the treated bifurcation lesion.

PMID- 16649249
TI  - Cross reactivity between many anti-human antibodies for their hamster homologs
      provide the tools to study the signal transduction pathway activated by asbestos
      and SV40 in the malignant mesothelioma model.
AB  - The aim of this study was to test the possibility of using human antibodies to
      study the pathogenic mechanism of SV40 and asbestos in a hamster mesothelioma
      model. The cellular lysates from human and hamster primary mesothelial cells were
      tested by Western blot analysis. All of the antibodies we tested (HGF, Notch,
      VEGF, Sp1, p53, PP2A, p-ERK1, p-c-jun, Fra1, Fra2, MMP1, MMP9, NFkappaB p65,
      IkappaB, GAPDH) cross-reacted with their hamster counterparts. These data
      indicate that hamster mesothelioma model and more in general hamster experimental
      model, can be used for functional studies because many mouse, rabbit, and goat
      monoclonal antibodies prepared against human antigens cross-react with their
      hamster counterparts.

PMID- 16649250
TI  - Persistent infection of hepatitis B virus is involved in high rate of p16
      methylation in hepatocellular carcinoma.
AB  - High rate of chronic hepatitis B virus (HBV) infection and p16 promoter
      methylation were found in the majority of hepatocellular carcinoma (HCC). To
      investigate the potential linkage between high rate of p16 methylation and HBV
      infection, p16 methylation was detected with methylation-specific polymerase
      chain reaction (PCR), and HBV markers were examined with real-time PCR and
      immunologic method. p16 methylation was detected in 5.5% of patients with
      hepatitis B, 9.1% of noncancerous liver, 36.6% of cirrhotic liver tissue, and
      70.5% of cancerous tissue of HCC, primarily in cirrhotic (46.7%) and cancerous
      tissue (90.6%) with HBV infection. In noncancerous tissue, p16 methylation could
      only be detected in samples with HBV infection, although no significant
      difference, the frequency of p16 methylation in noncancerous tissue with HBV
      infection was higher than those without it. The results showed that, in
      cancerous, cirrhotic, or noncancerous tissues, the frequency of p16 methylation
      in samples with HBV infection was higher than those without it, suggesting
      possible association between HBV infection and p16 methylation. The result of HBV
      DNA analysis showed that 96.1% (49/51) samples with p16 methylation also showed
      detectable HBV-DNA; it signifies that replication and/or integration of HBV may
      contribute to high rate of p16 methylation in hepatocarcinogenesis. Generally,
      these results indicate that persistent HBV infection may be associated with high
      rate of p16 methylation, and involved in development of HCC through this way.

PMID- 16649251
TI  - Soluble nickel inhibits HIF-prolyl-hydroxylases creating persistent hypoxic
      signaling in A549 cells.
AB  - Soluble nickel compounds are carcinogenic to humans although the mechanism by
      which they cause cancer remains unclear. One major consequence of exposure to
      nickel is the stabilization of hypoxia inducible factor-1alpha (HIF-1alpha), a
      protein known to be overexpressed in a variety of cancers. In this study, we
      report a persistent stabilization of HIF-1alpha by nickel chloride up to 72 h
      after the removal of nickel from the culture media. In addition, we show that the
      HIF-prolyl hydroxylases (PHD's) are inhibited when cells are exposed to nickel
      and that they remain repressed for up to 72 h after nickel is removed. We then
      show that nickel can inhibit purified HIF-PHD's 2 in vitro, through direct
      interference with the enzyme. Through theoretical calculations, we also
      demonstrate that nickel may be able to replace the iron in the active site of
      this enzyme, providing a plausible mechanism for the persistent inhibition of HIF
      PHD's by nickel. The data presented suggest that nickel can interfere with HIF
      PHD directly and does not inhibit the enzyme by simply depleting cellular
      factors, such as iron or ascorbic acid. Understanding the mechanisms by which
      nickel can inhibit HIF-PHD's and stabilize HIF-1alpha may be important in the
      treatment of cancer and ischemic diseases.

PMID- 16649252
TI  - Checkpoint kinase 1-mediated phosphorylation of Cdc25C and bad proteins are
      involved in antitumor effects of loratadine-induced G2/M phase cell-cycle arrest
      and apoptosis.
AB  - In this study, we first demonstrated that loratadine (LOR), a promising world
      widely used oral anti-histamine, effectively inhibits growth of tumors derived
      from human colon cancer cells (COLO 205) in an in vivo setting. In vitro study
      demonstrated that the anti-tumor effects of LOR in COLO 205 cells were mediated
      by causing G(2)/M phase cell growth cycle arrest and caspase 9-mediated
      apoptosis. Cell-cycle arrest induced by LOR (75 microM, 24 h) was associated with
      a significant decrease in protein levels of cyclin B1, cell division cycle (Cdc)
      25B, and Cdc25C, leading to accumulation of Tyr-15-phosphorylated Cdc2 (inactive
      form). Interestingly, LOR (75 microM, for 4 h) treatment also resulted in a rapid
      and sustained phosphorylation of Cdc25C at Ser-216, leading to its translocation
      from the nucleus to the cytoplasm because of increased binding with 14-3-3. We
      further demonstrated that the LOR-induced Cdc25C (Ser-216) phosphorylation was
      blocked in the presence of checkpoint kinase 1 (Chk1) specific inhibitor (SB
      218078). The cells treated with LOR in the presence of Chk1 specific inhibitor
      (SB-218078) were then released from G(2)/M arrest into apoptosis. These results
      implied that Chk1-mediated phosphorylation of Cdc25C plays a major role in
      response to LOR-mediated G(2)/M arrest. Although the Chk1-mediated cell growth
      arrest in response to DNA damage is well documented, our results presented in
      this study was the first report to describe the Chk1-mediated G(2)/M cell-cycle
      arrest by the histamine H1 antagonist, LOR.

PMID- 16649253
TI  - Thimerosal induces apoptosis and G2/M phase arrest in human leukemia cells.
AB  - Thimerosal is an organomercury compound with sulfhydryl-reactive properties. The
      ability of thimerosal to act as a sulfhydryl group is related to the presence of
      mercury. Due to its antibacterial effect, thimerosal is widely used as
      preservatives and has been reported to cause chemically mediated side effects. In
      the present study, we showed that the molecular mechanism of thimerosal induced
      apoptosis in U937 cells. Thimerosal was shown to be responsible for the
      inhibition of U937 cells growth by inducing apoptosis. Treatment with 2.5-5
      microM thimerosal but not thiosalicylic acid (structural analog of thimerosal
      devoid of mercury) for 12 h produced apoptosis, G(2)/M phase arrest, and DNA
      fragmentation in a dose-dependent manner. Treatment with caspase inhibitor
      significantly reduced thimerosal-induced caspase 3 activation. In addition,
      thimerosal-induced apoptosis was attenuated by antioxidant Mn (III) meso-tetrakis
      (4-benzoic acid) porphyrin (Mn-TBAP). These data indicate that the cytotoxic
      effect of thimerosal on U937 cells is attributable to the induced apoptosis and
      that thimerosal-induced apoptosis is mediated by reactive oxygen species
      generation and caspase-3 activation.

PMID- 16649254
TI  - Critical resources for gene therapy in Heart, Lung, and Blood Diseases Working
      Group.

PMID- 16649255
TI  - Conversion of biliary system to pancreatic tissue: complete plasticity or same
      organ?

PMID- 16649256
TI  - Late complications of NASH: a challenge for hepatologists.

PMID- 16649257
TI  - Mechanisms for resistance in soil.

PMID- 16649258
TI  - In memoriam; Dr. Gideon Rodan.

PMID- 16649259
TI  - Skin cancer epidemic. Take steps to avoid sun damage.

PMID- 16649260
TI  - Health tips. Managing heel pain.

PMID- 16649261
TI  - Older adults need to beware of sleeping pills.

PMID- 16649262
TI  - Rebound headaches. Stopping the cycle of pain.

PMID- 16649263
TI  - Shellfish. Off the cholesterol blacklist.

PMID- 16649264
TI  - Why do I need a prostate exam when my PSA levels are normal?

PMID- 16649265
TI  - Sequence conservation and correlation measures in protein structure prediction.
AB  - The rapid elucidation of protein sequences has allowed multiple sequence
      alignments to be calculated for a wide variety of proteins. Such alignments
      reveal positions that exhibit amino acid conservation--either of specific
      chemical groups in active and binding sites or of the more chemically inert
      hydrophobic residues that contribute to the protein core. The latter can provide
      constraints on the position of the protein chain and any local periodicity can
      suggest the type of secondary structure. Conservation measures, however, cannot
      provide specific pairwise packing information (each conserved hydrophobic
      position might pack against any other). However, if correlated changes between
      positions were observed then specific pairs of residue could be identified as
      interacting and therefore probably spatially adjacent. Most 'observations' of
      correlated changes have been anecdotal and of the few systematic studies that
      have been made, most have mistakenly incorporated a strong bias towards selecting
      conserved positions. When the conservation effect is separated (as best as
      possible) then little correlation signal remains to help identify adjacent
      positions.

PMID- 16649266
TI  - Surface contraction and expansion waves correlated with differentiation in
      axolotl embryos--I. Prolegomenon and differentiation during invagination through
      the blastopore, as shown by the fate map.
AB  - We have discovered a series of expansion and contraction, solitary waves that
      correlate with discrete steps of differentiation in the urodele amphibian axolotl
      embryo (Ambystoma mexicanum). Here we examine in detail the proposition that the
      blastopore is a set of differentiation waves. We superimposed the image of the
      axolotl fate map onto our digitized video images of normal gastrulation and
      matched the fate map to pigmentation irregularities on the embryo. We were then
      able to track the invagination of the fate map by tracking the variegated
      pigmentation on several embryos as gastrulation proceeded. We show a particular
      expansion and contraction wave sequence for every tissue in the blastula stage
      fate map and can now explain precisely why the fate map has the shape it does and
      its relationship to the embryo at subsequent stages. Each tissue can be assigned
      a differentiation code and placed on a hierarchical, binary differentiation tree.

PMID- 16649267
TI  - What is biology?
AB  - The following work compares two different ways of fractionating or abstracting
      from an organism: (a) a Mendelian way, which views the organism as a discrete
      bundle of phenotypic characters, each controlled by a corresponding genetic
      "factor", and (b) as a bundle of particulate molecular fractions, as envisaged by
      molecular biology. It is generally believed that the latter completely subsumes
      the former, and that it further serves to subsume all of biology into
      contemporary physics. We argue herein that the first of these assertions, if true
      at all, does not follow from an initial positing of an identity between the
      Mendelian gene and DNA sequence, and may well be false in general. In either
      case, the second assertion becomes false as well. This has profound consequences,
      not only for biology, but for the physics which is presumed to underlie it; it
      constitutes a part of the "new physics" which Erwin Schrodinger, in a famous
      essay [(1944) What is Life? Cambridge University Press, Cambridge], argued was
      inherent in biology.

PMID- 16649268
TI  - Science is in the eye of the beholder.
AB  - The way you view science limits the things that you can do "scientifically".
      Fortunately "science" is not a single thing but an evolving concept of how to
      cope with the world, and this flexible attitude towards science can be useful.
      The rigid view gives strict guidance on how to proceed "scientifically", while
      the more flexible approach allows for a greater range of response on your part.
      This paper gives some of the various views of what science is, in the hope that
      it will liberate you from being too strict without at the same time losing the
      useful guidance that "science" often provides.

PMID- 16649269
TI  - Towards single screening tests for brucellosis.
AB  - This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and
      a fluorescence polarisation assay (FPA), each capable of detecting antibody in
      several species of hosts to smooth and rough members of the genus Brucella. The I
      ELISA uses a mixture of smooth lipopolysaccharide (SLPS) and rough
      lipopolysaccharide (RLPS) as the antigen, and a recombinant protein A/G
      conjugated with horseradish peroxidase as the detection reagent. When using
      individually determined cutoff values, the SLPS/RLPS combined-antigen I-ELISA
      detected antibody in slightly more animals exposed to SLPS or to RLPS than did I
      ELISA procedures using each individual antigen separately. Similarly, the assay
      using combined antigens detected antibody in slightly fewer animals not exposed
      to Brucella sp. When a universal cutoff of 10% positivity was used (relative to
      strongly positive control sera of each species), the overall performance index
      (percentage sensitivity plus percentage specificity) value decreased by 1.0 (from
      199.4 to 198.4). In the FPA, it was not possible to use a universal cutoff
      without significant loss of performance. The overall sensitivity value for the
      FPA using the combined FPA antigen was 1.0% lower than using the O-polysaccharide
      (OPS) from SLPS and 9.1% higher than using the core antigen (CORE) from RLPS.
      When the combined antigen was used, the FPA specificity was slightly higher
      (1.2%) than from only the OPS, and considerably higher (12.6%) than the CORE.
      Overall, both the I-ELISA and the FPA with combined antigens were suitable as
      screening tests for all species of Brucella in the animal species tested.

PMID- 16649270
TI  - A two step chemo-biotechnological conversion of polystyrene to a biodegradable
      thermoplastic.
AB  - A novel approach to the recycling of polystyrene is reported here; polystyrene is
      converted to a biodegradable plastic, namely polyhydroxyalkanoate (PHA). This
      unique combinatorial approach involves the pyrolysis of polystyrene to styrene
      oil, followed by the bacterial conversion of the styrene oil to PHA by
      Pseudomonas putida CA-3 (NCIMB 41162). The pyrolysis (520 degrees C) of
      polystyrene in a fluidized bed reactor (Quartz sand (0.3-0.5 mm)) resulted in the
      generation of an oil composed of styrene (82.8% w/w) and low levels of other
      aromatic compounds. This styrene oil, when supplied as the sole source of carbon
      and energy allowed for the growth of P. putida CA-3 and PHA accumulation in shake
      flask experiments. Styrene oil (1 g) was converted to 62.5 mg of PHA and 250 mg
      of bacterial biomass in shake flasks. A 1.6-fold improvement in the yield of PHA
      from styrene oil was achieved by growing P. putida CA-3 in a 7.5 liter stirred
      tank reactor. The medium chain length PHA accumulated was comprised of monomers
      6, 8, and 10 carbons in length in a molar ratio of 0.046:0.436:1.126,
      respectively. A single pyrolysis run and four fermentation runs resulted in the
      conversion of 64 g of polystyrene to 6.4 g of PHA.

PMID- 16649271
TI  - Take your pills, all your pills: drug makers nag patients to stay the course.

PMID- 16649272
TI  - A hunt for genes that betrayed a desert people.

PMID- 16649273
TI  - Seeking ancestry, and privilege, in DNA ties uncovered by tests.

PMID- 16649274
TI  - Citing risk of missteps, judges set hurdles for lethal injection.

PMID- 16649275
TI  - State proposes using device, not doctors, in execution.

PMID- 16649276
TI  - F.D.A. dismisses medical benefit from marijuana.

PMID- 16649278
TI  - F.D.A.'s report illuminates wide divide on marijuana.

PMID- 16649279
TI  - End-of-life lawmaking.

PMID- 16649280
TI  - Enter the neuro-economists: why do investors do what they do?

PMID- 16649281
TI  - Study cites links to firms by psychiatrists.

PMID- 16649282
TI  - Court backs Briton's right to a costly drug.

PMID- 16649283
TI  - North Carolina, using medical monitoring device, executes killer.

PMID- 16649284
TI  - Judge allows device to be used for monitoring lethal injection.

PMID- 16649285
TI  - Death after RU-486.

PMID- 16649286
TI  - The epidemiology of influenza in children hospitalized in Canada, 2004-2005, in
      Immunization Monitoring Program Active (IMPACT) centres.

PMID- 16649287
TI  - Outbreak of Salmonella typhimurium phage type U302 in Ontario, spring 2005.

PMID- 16649288
TI  - Dissenting viewpoints. Healthcare IT developers wary of federal prototypes for
      nation network.

PMID- 16649289
TI  - Influenza in Canada--2004-2005 season.

PMID- 16649290
TI  - Wild birds, poultry, and avian influenza.

PMID- 16649291
TI  - Expected benefits of pneumococcal vaccination in Canadian infants and children <
      5 years old.

PMID- 16649292
TI  - Sub-regional variations in the epidemiology of Neisseria gonorrhoeae in a large
      urban region in Alberta, Canada: results from spatial analyses using routinely
      collected surveillance data.

PMID- 16649293
TI  - An interview by Paul C Adams. Colorectal cancer screening: opportunistic or
      organized?

PMID- 16649294
TI  - Influenza in Canada: 2005-2006 season update.

PMID- 16649295
TI  - Adverse events after vaccination with dTap in high school students who have
      previously been vaccinated with d2T5.

PMID- 16649297
TI  - The hidden economic benefits of childhood immunizations in Capital Health region,
      Alberta.

PMID- 16649296
TI  - Report on a workshop to develop a framework for microbial food safety policy
      research--Ottawa, 7- 8 March, 2005.

PMID- 16649298
TI  - Life on the edge.

PMID- 16649299
TI  - Breast cancer.

PMID- 16649300
TI  - Uptake of spirometry training by GPs.

PMID- 16649301
TI  - Clinical teaching.

PMID- 16649302
TI  - Fetal alcohol syndrome.

PMID- 16649303
TI  - Primary orthostatic tremor in giant breed dogs.

PMID- 16649304
TI  - MRSA--controlling expose and eliminating infection.

PMID- 16649305
TI  - On: a boycott by passport.

PMID- 16649306
TI  - Statement.

PMID- 16649307
TI  - [Effect of Helicobacter pylori eradication on microsatellite instability and
      point mutation of K-ras codon 12 gene in intestinal metaplasia].

PMID- 16649308
TI  - [CagA tyrosine phosphorylation motif structure and SHP-2 binding ability of
      Helicobacter pylori studied in stomach cancer and duodenal ulcer cell lines].

PMID- 16649309
TI  - [Role of macrophage migration inhibitory factor in pathogenesis of post
      menopausal osteoporosis].

PMID- 16649310
TI  - [Alleviating effect of the sense of coherence(SOC)in mothers having abusive
      experience who abuse their children].

PMID- 16649311
TI  - [Role of osteopontin in tendon remodeling due to decrease of mechanical stress].

PMID- 16649312
TI  - Rehabilitation in home care: new Joint Commission accrediting standards.
AB  - The Joint Commission's new set of rehabilitation standards is applicable only if
      the organization provides rehabilitation services as described in their scope of
      service. Admission to home care services requires an assessment of the patient's
      functional status that may in turn lead to the need for referral for
      rehabilitation services. A thorough review of the standards integrating the
      information in this article can help home care managers to understand and comply
      with the rehabilitation standard and identify how a surveyor may review an agency
      for compliance. These new standards can guide organizations in providing the
      quality oversight necessary to achieve goals that reflect positive patient
      outcomes.

PMID- 16649313
TI  - Encouraging research in home care: learning from agency staff and family
      caregivers.
AB  - It is clear that research is an increasing role of managers and is crucial to the
      financial and clinical success of a home health agency. This article has
      described the important considerations and approaches managers must consider to
      integrate research effectively. By following one agency's involvement with a
      researcher on a project, strategies emerge that managers can use to integrate
      research with staff in everyday practice.

PMID- 16649314
TI  - Strategic recruitment newspaper tips.

PMID- 16649315
TI  - PPS management strategies and objectives: Keys for success!

PMID- 16649316
TI  - Using PI to reinvent your skin care program.

PMID- 16649317
TI  - IPS versus PPS: a case study.

PMID- 16649318
TI  - Efforts to improve patient care outcomes continue at a strong pace.

PMID- 16649319
TI  - The CNN vs. CNN debate continues.

PMID- 16649320
TI  - Certification and credentialing--what does it mean to the patient?

PMID- 16649321
TI  - Inappropriate use of dialysis for some elderly patients: nephrology nurses'
      perceptions and concerns.
AB  - The purpose of this study was to determine what percentage of elderly patients
      (age 65 years and older) nephrology nurses (NN) believe should not be dialyzed
      and to identify NN percep tions and concerns about the inappropriate use of
      dialysis for these patients. The design was descriptive using a cross-sectional
      survey instrument. Data was collected in 1996 from 393 NN (44% response rate),
      with a mean age of 41 years and 9 years of dialysis experience. The sample was
      1,000 NN randomly selected from 7,000 members of the American Nephrology
      Nurses'Association (ANNA) who selected hemodialysis as a special area of
      interest. Quantitative analysis of respondents revealed that NN felt that 15% of
      elderly dialysis patients (EDP) should not be dialyzed, and 80% were troubled by
      decisions to start dialysis for some elderly patients. Content analysis of
      qualitative responses supported the NN concerns revealed in the quantitative
      analysis. Five themes with interrater reliability of > 98% were identified:
      qualiy of life (QoL), patient/family inadequate knowledge, patient influences on
      decision making age, and other (cost/legal reasons). QoL issues accounted for 75%
      of NN responses. Statistical analyses including an ANOVA, t-tests, and chi square
      failed to identify relationships between themes and demographic factors, such as
      age, gender, years of experience, education level, unit profit status, and type
      of staff position. The researchers conclude that NN believe dialysis is
      inappropriate for a significant percentage of EDP, these perceptions and concerns
      are widespread, and QoL issues are key factors in decisions to withhold or
      withdraw dialysis. NN may decrease the inappropriate use of dialysis by
      identifying QoL factors for EDP, facilitating discussions with family members and
      nephrologists, and continuing to advocate for the rights of EDP with poor QoL.

PMID- 16649322
TI  - Herbal remedies, nephropathies, and renal disease.
AB  - The use of herbal remedies is becoming increasingly popular in the United States.
      Research has shown that herbal remedy use may be associated with acute renal
      failure. In addition, the use of herbal remedies may be detrimental for the
      patient with compromised renal function. Patients with renal insufficiency or
      renal failure may be at risk for further kidney damage as well as complications
      related to interactions of herbal remedies with complex renal therapy regimens.
      This article will describe the escalating use of herbal therapy and the hazards
      of herbal remedy use among patients.

PMID- 16649323
TI  - Dialyzer reprocessing: improved treatment quality and increased dialyzer reuse
      using a team approach.
AB  - Use of the performance improvement process can yield unexpected positive results.
      Through the implementation of performance improvement concepts, the Dialysis
      Centers of Dayton LLC East was able to increase the average dialyzer reuse number
      and achieve economical benefits while improving the quality of patient care
      delivered. Employment of the team approach, staff education, and communication
      was vital to the success of this Over the last 10 years, the use of dialyzer
      reprocessing has steadily increased in dialysis units across the country. If the
      reuse average was down in a unit, it was not uncommon to look to the reuse staff
      for an explanation, since it is "their" job to keep the numbers up. After
      consultation with a Minntech representative, the Dialysis Centers of Dayton LLC
      East staff discovered that the most effective methods to increase the average
      reuse number were those implemented on the dialyzer before it ever reached the
      reprocessing area. Several technical changes were initiated, including the use of
      standardized heparin protocols, all of which contributed to the improvement in
      the reuse average. Although some of these changes had been done previously, they
      were not implemented and reviewed according to the formal performance improvement
      model. Two methods for calculating the reuse average were employed. Over a 12
      month time frame, reuse numbers increased from 7.1 and 7.5 to 36.6 and 18.1,
      respectively (utilizing the Hartline [1996] and conventional method of reuse
      calculation). Review of patient adequacy showed no detrimental effects and a
      slight improvement in the percentage of patients with a Kt/V of more than 1.2.
      Focusing on performance improvement in the reprocessing area has yielded many
      benefits to both patients and staff.

PMID- 16649324
TI  - Tuberculosis screening in a dialysis program.
AB  - Patients with end stage renal disease (ESRD) are at high risk for contracting
      tuberculosis (TB), therefore, routine screening of these patients is recommended
      This article describes the steps used to design and implement a TB screening
      protocol in a new regional dialysis program. The results showed a high rate of
      skin test positivity and, therefore, of infection. Over half of the patients
      tested were found to be anergic, necessitating a chest x-ray for 70% of the
      patients. In light of these findings, the annual skin testing of all patients,
      which was originally planned, has been changed to testing upon admission to the
      program, providing a baseline with which to compare subsequent skin tests.

PMID- 16649325
TI  - Blood flow rate effects in continuous venovenous hemodiafiltration on blood urea
      nitrogen and creatinine reduction.
AB  - The effect of blood flow rates (BFRs) in continuous venovenous hemodiafiltration
      (CVVHDF) on the clearances of blood urea nitrogen (BUN) and creatinine was
      studied using a retrospective chart review. Fifteen patients, 9 males and 6
      females aged 50-85 years, were included in the study. Each patient had a primary
      cardiovascular diagnosis with acute renal failure (ARF) and was treated with
      CVVHDF on the Gambro PRISMA continuous renal replacement therapy (CRRT) machine
      using the COBE AN69 filter. Independent sample t-test, simple linear regression,
      ANOVA, and multiple comparisons were used. Simple linear regression revealed that
      BUN, creatinine, and difference in creatinine (DIFFCRTN) were best predicted by
      the number of hours of treatment. For every hour of treatment the BUN decreased
      by .08 mg/dl, the creatinine decreased by .01 mg/dl, and the DIFFCRTN increased
      by .01 mg/dl. The study concluded that patients on CVVHDF for greater than 72
      hours had the greatest changes in BUN and creatinine when a BFR between 135-145
      cc/min was used.

PMID- 16649326
TI  - Anemia management: recognizing opportunities and improving outcomes through
      nursing interventions.
AB  - In the symposium "Anemia Management: Recognizing Opportunities and Improving
      Outcomes Through Nursing Interventions," Gail Wick discussed the nephrology nurse
      as a clinical change agent in the management of anemia of chronic renal failure.
      Matthew Lewis discussed the profile of sodium ferric gluconate complex, a new
      parenteral iron product, and Jamie Foret described his clinic's experience and
      research with this product. These discussions highlight how nurses, using
      effective and safe tools such as sodium ferric gluconate complex, can improve
      outcomes for hemodialysis patients.

PMID- 16649327
TI  - Assessing hyporesponse to Epoetin alfa: an algorithm approach: case study of the
      anemic patient.
AB  - Nephrology nurses who manage the anemia of end-stage renal disease (ESRD) are
      often responsible for monitoring, assessing, and intervening to maintain
      hemoglobin (Hb) and hematocrit (Hct) levels within their facility target range.
      Consistency in anemia-related outcomes is sometimes compromised when patients
      exhibit hyporesponse to Epoetin alfa therapy-defined as a temporary or chronic
      Hb/Hct level below the target range. Early detection of hyporesponse and
      correction of conditions that are affecting erythrocyte development can sometimes
      be delayed if clinicians are unable to promptly identify a causative etiology.
      This article reviews a hyporesponse algorithm worksheet that nurses can use to
      identify the cause(s) of hyporesponse and guide clinical decision making.

PMID- 16649328
TI  - Successful use of sodium ferric gluconate in sucrose in a patient with multiple
      drug allergies.
AB  - This is not a controlled study but an anecdotal experience that resulted in
      improved outcomes in a patient with multiple allergies, including iron dextran.
      Target Hct/Hgbs were attained and exceeded, although iron indices were not fully
      achieved. Infections demonstrated RE blockade and failure of TSAT to reach target
      range. The multidisciplinary team's successful decision to trial SFG in a
      medically complex patient allowed profound iron deficiency to be treated safely
      and effectively, which was not possible prior to the availability of an alternate
      iron preparation. It is rewarding to have the option to offer a medication that
      improves patients' status and enhances outcomes. Mr. C. was less tired and had
      more energy following his first and subsequent courses of therapy. "I couldn't
      believe how tired I was without realizing it until after I finished a course of
      iron therapy. I just thought that was my quality of life on dialysis. It's much
      better now and I have more energy." Such comments justify our efforts on our
      patients' behalf.

PMID- 16649329
TI  - Developing a dialysis rehabilitation program.

PMID- 16649330
TI  - Marketing your ESRD program: A presentation by Deborah Johnson.

PMID- 16649331
TI  - Hepatitis and transfusions.
AB  - Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are major causes of liver
      disease. Chronic infection with these viruses often leads to chronic liver
      disease, including cirrhosis or primary hepatocellular carcinoma (HCC). Concern
      is growing among patients and health care workers about possible transmission of
      bloodborne pathogens during medical procedures. This fear has primarily been
      focused on nosocomial transmission of human immunodeficiency virus (HIV), but
      other bloodborne infectious agents may also be transmitted during procedures.
      Chief among these are the hepatitis viruses, particularly HBVand HCV, both of
      which are significantly more widespread than HIV Circumstantial evidence suggests
      that hemodialysis, per se, is an important risk factor for infection with HCV.

PMID- 16649336
TI  - Therapeutic drug monitoring--its highs and lows (peaks and troughs).

PMID- 16649337
TI  - Acute renal failure related to rhabdomyolysis: pathophysiology, diagnosis, and
      collaborative management.
AB  - Acute renal failure related to exertional rhabdomyolysis is a medical condition
      that, if not diagnosed correctly and treated aggressively, can lead to serious
      dysfunction and may result in death. Although the history is invaluable in
      diagnosing this condition, it must be confirmed by laboratory testing. The
      sometimes subtle manifestations of exertional (non-traumatic) rhabdomyolysis make
      it mandatory that the health care team is able to recognize the signs and
      symptoms and understand the pathophysiology for prompt treatment and referral.

PMID- 16649338
TI  - Continuous renal replacement therapy: dialytic therapy for acute renal failure in
      intensive care.
AB  - Acute renal failure (ARF) is a common complication of critically ill patients in
      today's intensive care units. Intermittent renal replacement therapy for these
      types of patients may be limited or ineffective due to the critical nature of
      their illness. Volume overload and hemodynamic instability are complications that
      may not be treated adequately with conventional forms of dialysis, such as
      hemodialysis or peritoneal dialysis. Continuous renal replacement therapy (CRRT)
      is rapidly gaining ground as the treatment of choice for ARF in the intensive
      care unit (ICU) due to its slow, gentle nature of water and solute removal
      Critical care nurses are responsible for monitoring this therapy, but a
      collaborative effort with nephrology nurses' expertise and background in dialysis
      therapies is a key ingredient in implementation of a successful CRRT program.
      This article will review the causes of ARF, the history of CRRT, current
      treatment options, trends, and implementation of a successful CRRT program.

PMID- 16649339
TI  - End-stage renal disease in African-Americans.
AB  - The African-American community comprises approximately 12.4% of the total
      American population, but they account for 30.8% of patients diagnosed with end
      stage renal disease (ESRD). This article focuses first on theories explaining the
      high prevalence of ESRD in African-Americans. Two major causes of ESRD,
      hypertension and Type II diabetes, and their relationship to African-Americans
      are explored. Morbidity, familial risk and new incidences are addressed. Lastly,
      a screening project for African-Americans at risk for ESRD is proposed.

PMID- 16649340
TI  - World Foundation for Renal Care: helping acute and chronic renal failure patients
      and their families worldwide: an interview with Geraldine Biddle.
AB  - In this interview, Geraldine Biddle, president and co-founder of the World
      Foundation for Renal Care (WFRC), describes the organization's beginnings and the
      progress it has made toward its mission and vision. Ms. Biddle also details the
      historic involvement of ANNA informing WFRC and participating in its activities.
      Founded in 1997, the WFRC has its world headquarters in London and currently has
      three ANNA past presidents on its Board of Directors.

PMID- 16649341
TI  - Access thrombosis, hospitalization, and hematocrit level in hemodialysis
      patients.
AB  - Are occurrences of vascular access thrombosis and hospitalization higher in
      hemodialysis patients with hematocrits (Hcts) > 36% compared to those < 36%? This
      12-month retrospective study included 30 male hemodialysis patients who received
      erythropoietin (rHuEPO) for at least 6 months. Sixty percent (n = 18) had
      arteriovenous fistulas and 40% (n = 12) had polytetrafluoroethylene grafts. The
      mean age was 59.6 years. Twenty patients during 216 patient months had a mean Hct
      < 36% with five thromboses (2.3%). Ten patients during 118 patient months had a
      mean Hct > 36% with four thromboses (3.4%). There was no statistically
      significant difference between the thrombosis rates in the two groups. There were
      four hospitalizations in 118 patient months in the > 36% group (3.4%). There were
      33 hospitalizations in 216 patient months in the < 36% group (15.3%). This is 4.5
      times higher than the > 36% group. Our data suggest that Hcts > 36% are not
      associated with increased thrombosis and are associated with lower
      hospitalization rates.

PMID- 16649342
TI  - Supporting epoetin alfa stimulated erythropoiesis: identifying appropriate iron
      levels: case study of the anemic patient.
AB  - Stimulation of red blood cell precursors by Epoetin alfa results in a
      predictable, dose-dependent increase in red blood cell mass. Iron is an important
      substrate that supports red blood cell and hemoglobin development. Patients who
      receive Epoetin alfa therapy typically require intravenous iron supplementation
      to ensure proper red cell formation. Target and ceiling iron levels should be
      determined on the basis of safety considerations, the predicted clinical
      response, and individual patient replacement needs. Nurses can use clinical
      parameters such as body weight, baseline and target hemoglobin values, and iron
      losses from blood and other sources to estimate iron replacement doses, thereby
      providing a guide for appropriate iron replacement.

PMID- 16649343
TI  - Impact of inflammation on nutrition, iron status, and erythropoietin
      responsiveness in ESRD patients.
AB  - Since many end stage renal disease (ESRD) patients experi inflammation,
      malnutrition, and anemia, the interplay of these processes should be considered
      in the approach to patients treated with erythropoietin (EPO). This article
      reviews the interrelationship between these factors. The systemic inflammatory
      response caused by exposure to inflammatory stimuli results in anorexia and
      metabolic disturbances leading to protein calorie malnut tion as well as
      sequestration of iron and hyporesponsiveness to EPO. The implications of these
      effects and possible strategies to optimize anemia management in the presence of
      these conditions are discussed.

PMID- 16649344
TI  - Sirolimus: mammalian target of rapamycin inhibitor to prevent kidney rejection.
AB  - Current immunosuppressive therapies are effective but can be associated with
      significant adverse reactions. Sirolimus works differently from the
      immunosuppressants currently available, and except for increased lipid levels,
      the adverse reaction profile of sirolimus does not appear to overlap to any great
      extent with that associated with cyclosporine or tacrolimus. While additional
      research is needed, the initial clinical data in kidney recipients suggest that
      sirolimus, in combination with cyclosporine or tacrolimus, might have the
      potential to reduce the frequency of rejection episodes, permit reductions in
      cyclosporine or tacrolimus dosage, and permit steroid withdrawal (Kelly, 1999).

PMID- 16649345
TI  - Violence in the workplace.

PMID- 16649346
TI  - Dialysis facility-specfic reports for consumers.

PMID- 16649347
TI  - Prevention of needlestick injuries: a matter of ethics.

PMID- 16649348
TI  - Effects of chimerism on graft-versus-host disease, disease recurrence, and
      survival after HLA-identical marrow transplantation in Iran.
AB  - BACKGROUND: The coexistence of recipient's and donor's hematopoietic systems
      after allogeneic marrow transplantation is called mixed chimerism. OBJECTIVE: The
      objective of this study was to evaluate the effects of MC on graft-versus-host
      disease (GVHD), disease recurrence, and survival after HLA identical marrow
      transplantation in a transplant center in Iran. METHODS: The association of MC
      with acute GVHD, disease recurrence, survival, and relapse-free survival was
      investigated in 91 patients who underwent either bone (n = 12) or peripheral
      blood (n = 79) HLA-identical marrow transplantation. Chimerism was assessed using
      multiplex amplification of short tandem repeats (STR). Patients had thalassemia
      (n = 19), acute myelogenous leukemia (AML) (n = 29), acute lymphocytic leukemia
      (ALL) (n = 20), chronic myelogenous leukemia (CML) (n = 18), and other diseases
      (n = 5). The median age was 21 (range: 3 - 50) years. There were 38 (42%) female
      and 53 (58%) male participants. Conditioning was made through busulfan plus
      cyclophosphamide in 34 patients; busulfan plus fludarabin in 51 patients; and
      busulfan plus fludarabin plus antithymocyte globulin in 6 patients. The median
      follow-up was 13 months. RESULTS: On day +30, complete chimerism (CC) was
      observed in 72 (79%) patients, MC in 15 (17%), and no chimerism in 4 patients.
      The incidence of acute GVHD was significantly (P = 0.01) lower in mixed chimeras
      than in complete chimeras. There was no significant difference in acute GVHD
      grade (I, II vs. III, IV) between the two groups. The incidence of relapse was
      18%. There was no difference in relapse rate between MC and CC groups. Overall
      survival was 89%. There was no significant difference in the overall survival
      between MC and CC group (96% vs. 85%, respectively). Relapse-free survival was
      80% that was not significantly different between the two groups. CONCLUSION:
      Despite some previous reports, we found no significant difference in the survival
      and relapse rates between MC and CC groups.

PMID- 16649349
TI  - An epidemiological study of obsessive-compulsive disorder among high school
      students and its relationship with religious attitudes.
AB  - BACKGROUND/OBJECTIVE: Considering the importance of mental health in adolescents,
      we studied the prevalence of obsessive-compulsive disorder (OCD) in this age
      group and determined its relationship with their religious attitudes. METHODS: In
      this survey, 293 students at different grades were selected using a multiphasic
      cluster sampling method. Subjects were asked to complete demographic, Yale-Brown
      scale, and religious attitude questionnaires. Those with scores higher than the
      cutoff value were interviewed by a psychiatrist, based on the DSM-IV criteria.
      Data were analyzed by chi2 and Student's t-test. RESULTS: The prevalence of OCD
      was 8.87% (5.1% in boys and 3.75% in girls). The majority of patients with OCD
      were from urban regions and had a positive family history in their first- or
      second-degree relatives. Nonetheless, there was no relationship between OCD and
      religious attitudes. CONCLUSION: The prevalence of OCD found in our study was
      higher than many of those reported earlier. Religious attitudes could only affect
      the contents of obsession and compulsion.

PMID- 16649350
TI  - Efficacy of folic acid therapy for prevention of in-stent restenosis: a
      randomized clinical trial.
AB  - BACKGROUND: It is known that there is an association between elevated total
      plasma homocysteine level and restenosis after percutaneous coronary angioplasty.
      OBJECTIVE: To evaluate the effect of lowering plasma homocysteine levels on the
      rate of restenosis after stent-percutaneous coronary angioplasty. METHODS: Folic
      acid (1 mg) or placebo was administered to 200 patients (mean +/- SD age of 54 +/
      9 years) for 3 months, after successful coronary angioplasty in a double-blind
      randomized clinical trial. The primary end point was restenosis within six
      months, as assessed by quantitative coronary angiography after positive exercise
      tolerance test. The secondary end point was a composite of major cardiac events.
      RESULTS: Base line characteristics and initial angiographic results after stent
      percutaneous coronary angioplasty were similar in the two study groups. The rate
      of restenosis showed no significant difference in the two groups (5% in placebo
      vs. 10% in folic acid groups; P = 0.141), as there was the need for
      revascularization of the target lesion (4% in both groups; P = 0.766).
      CONCLUSION: Treatment with folic acid does not decrease the rate of restenosis
      and need for revascularization of the target lesion after stent-percutaneous
      coronary angioplasty.

PMID- 16649351
TI  - Mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.
AB  - BACKGROUND: There are few treatment options for patients with secondary
      progressive and worsening relapsing-remitting multiple sclerosis. Mitoxantrone is
      an antineoplastic drug, recently approved for treatment of multiple sclerosis.
      Mitoxantrone is, however, associated with dose-related cardiotoxicity, which
      limits its use. OBJECTIVE: To investigate the possible cardiotoxicity of
      mitoxantrone in multiple sclerosis. METHODS: We studied 96 patients with
      worsening relapsing-remitting or secondary progressive multiple sclerosis, to
      evaluate cardiotoxicity within one year of mitoxantrone therapy. This study was
      performed in the Multiple Sclerosis Clinic of Isfahan University of Medical
      Sciences from October 2003 through October 2004. Analysis of mitoxantrone therapy
      (12 mg/m2), in terms of cardiac toxicity, was conducted on patients who received
      at least 4 doses. Cardiac assessment was carried out every 6 months with
      electrocardiogram, as well as a spectral and color-flow Doppler echocardiographic
      examination at the time of enrollment and 6 and 12 months later. RESULTS: Ninety
      six patients were assessed over 12 months. There was no evidence of clinically
      significant cardiac dysfunction. Three patients had a left ventricular ejection
      fraction of <10% of the base-line value and three had <50%. CONCLUSION:
      Mitoxantrone (12 mg/m2) is effective and generally well tolerated by patients
      with worsening relapsing-remitting and secondary progressive multiple sclerosis.
      Our findings suggest that the risk for developing cardiotoxicity is low in
      patients with multiple sclerosis within one year of the treatment with
      mitoxantrone.

PMID- 16649352
TI  - Maternal and neonatal outcomes in pregnant women with immune thrombocytopenic
      purpura.
AB  - BACKGROUND: The aim of this study was to evaluate the outcome of pregnancies in
      Iranian women with immune thrombocytopenic purpura (ITP). METHODS: In a
      historical cohort study, maternal and neonatal outcomes were studied in 30
      pregnant women with ITP at a hospital in Tehran, from January 1994 through
      November 2003. RESULTS: Twenty-two cases were diagnosed as ITP before and 8
      during pregnancy. Thrombocytopenia (platelet count <150 x 10(9)/L) occurred in 22
      pregnancies. Eleven (37%) had vaginal delivery and 19 (63%) underwent elective
      cesarean section. Eight women had severe postpartum hemorrhage. All live-born
      neonates were delivered in good condition at term. Neonatal thrombocytopenia
      occurred in 20 (67%) neonates. No bleeding complications occurred in any of the
      neonates. CONCLUSION: The outcome of pregnancy in pregnant women with ITP is
      generally good. Cesarean section should only be performed for obstetric
      indications. Postpartum hemorrhage is common in these women. Postpartum
      hemorrhage is unrelated to the mode of delivery. Severe thrombocytopenia and
      bleeding in the offspring are uncommon.

PMID- 16649353
TI  - Acute lead exposure and contraction of rat isolated aorta induced by D1
      dopaminergic and alpha-adrenergic drugs.
AB  - BACKGROUND/OBJECTIVE: In the present study, the effect of acute lead exposure in
      the presence and absence of dopamine or alpha (alpha)-adrenoceptor agents on
      contractile response of rat isolated thoracic aorta was studied. METHODS: Male
      Wistar rats were used in all experiments. Thoracic aorta was carefully removed,
      cleaned, and cut into 2-mm thick rings. The rings were mounted for measurement of
      isometric contractions in a tissue bath containing 10 mL of Kreb's solution at 37
      - 38 degrees C. The following drugs were used: lead chloride, dopamine,
      phenylephrine, prazosin, clonidine, yohimbine, and SCH23390. One-way analysis of
      variance (ANOVA) and Student's t-test were used for statistical analyses. P <
      0.05 was considered significant. RESULTS: The alpha1-adrenoceptor antagonist
      (prazosin), alpha2-adrenoceptor antagonist (yohimbine), or dopamine D1 receptor
      antagonist (SCH23390), did not elicit any response. Combination of lead with
      dopamine, phenylephrine, or clonidine did not show any potentiation. SCH23390,
      prazosin, and yohimbine decreased the contraction induced by lead. SCH23390
      decreased the contraction induced by dopamine, or lead plus dopamine. Prazosin
      reduced the contraction induced by phenylephrine or lead plus phenylephrine.
      Yohimbine attenuated the response induced by clonidine or lead plus clonidine.
      CONCLUSION: alpha1, alpha2, and D1 dopamine receptor mechanisms could have a role
      in lead-induced contraction.

PMID- 16649354
TI  - The status of pelvic supporting organs in a population of iranian women 18 - 68
      years of age and possible related factors.
AB  - BACKGROUND/OBJECTIVE: The status of pelvic supporting organs and possible related
      factors in a population of Iranian women, 18 - 68 years of age, were studied in
      primary health care centers. METHODS: In this cross-sectional study, 3,730 women
      were visited in three primary health care centers. The status of their pelvic
      supporting organs was measured according to the pelvic organ prolapse
      quantification system. Stages of prolapse were evaluated for trends in terms of
      various variables, using the Pearson chi2 statistical test. Demographic and
      obstetric factors were tested for potential confounding variables with logistic
      regression analysis. RESULTS: The mean age was 36 (range: 18 - 68) years. The
      overall distribution of pelvic organ prolapse was as follows: stage 0, 47%; stage
      1, 23.1%; stage 2, 18.3%; and stage 3, 11.6%. Based on logistic regression
      analysis, age > or =50 years, menopause, gravidity >3, parity >3, number of
      vaginal deliveries >3, history of operative delivery, history of vaginal delivery
      without episiotomy, and home delivery were found to be independent risk factors
      for development of pelvic organ prolapse. CONCLUSION: The overall rate of
      prolapse was 53%, with most subjects having stage 1 or 2. Several factors
      influence development of pelvic organ prolapse.

PMID- 16649355
TI  - A novel scoring system for identifying high-risk patients undergoing carotid
      stenting.
AB  - BACKGROUND/OBJECTIVE: In patients with severe concurrent coronary and carotid
      artery disease, two different treatment strategies may be used: simultaneous
      endarterectomy and coronary bypass surgery, and carotid stenting with delayed
      coronary bypass surgery after a few weeks. To evaluate the safety and efficacy of
      carotid stenting with delayed coronary bypass surgery after a few weeks in
      patients referred to Tehran Heart Center, Tehran, Iran and to determine the
      independent predictors that may be used to identify the appropriate treatment
      plan for such patients. METHODS: This prospective study was performed from
      December 2003 through October 2004. Symptomatic patients with >60% stenosis and
      asymptomatic patients with >80% stenosis were included in this study. The risks
      and benefits of carotid stenting were explained. Patients were excluded from the
      study if any of the following was applicable: age > or =85 years, history of a
      major stroke within the last week, pregnancy, intracranial tumor or arteriovenous
      malformation, severely disabled as a result of stroke or dementia, and
      intracranial stenosis that exceeded the severity of the extracranial stenosis.
      Thirty consecutive patients who underwent carotid stenting were enrolled in this
      study. RESULTS: The mean +/- SD age of patients was 66.3 +/- 8 years. The
      procedural success rate was 96.7%. During a mean +/- SD follow-up period of 5.6
      +/- 3.2 months, 4 (17%) deaths occurred; none of which were attributed to a
      neurologic causes. Moreover, 1 (3%) patient developed a minor nonfatal stroke
      with transient cognitive disorder. Most of patients (80%) with major
      complications acquired a score of > or =26. CONCLUSION: To reduce the rate of
      carotid stenting complications in high-risk patients with heart disease, to
      optimize the patient selections, and to determine the best treatment strategy,
      based on the clinical and lesion characteristics of patients, we proposed a new
      scoring system.

PMID- 16649356
TI  - An experience with angioplasty and stenting of carotid artery stenosis with
      embolic protection devices.
AB  - BACKGROUND: Carotid artery stenting has recently been recommended as an
      alternative to carotid endarterectomy by some clinicians. OBJECTIVE: To evaluate
      success rate, as well as in-hospital and 30-day adverse events in our first
      experience in Iran for carotid artery stenting with protection devices. METHODS:
      From December 2003 through July 2004, we performed 12 consecutive (9 males and 3
      females) carotid artery stenting procedures. The patients had a mean age of 62
      (range: 46 - 78) years. Indications for carotid artery stenting included primary
      lesions in all patients, stenosis > or =50% in symptomatic, and stenosis > or
      =80% in asymptomatic patients. RESULTS: Carotid artery stenting was technically
      successful in all 12 patients. The mean +/- SD severity of stenosis before
      carotid artery stenting was 85 +/- 14% as compared with 15 +/- 10% after the
      procedure. No periprocedural death occurred. No in-hospital or 30-day minor or
      major stroke/death was observed. CONCLUSION: Percutaneous stenting of the carotid
      artery stenosis, when a cerebral protection device is used, is feasible and
      effective but not without technical difficulties and potential complications. We,
      therefore, recommend carotid artery stenting for patients who are at high risk
      for undergoing carotid endarterectomy. Nevertheless, a long-learning curve may be
      needed for anyone who wishes to start this technique.

PMID- 16649357
TI  - The influence of maternal ketonuria on fetal well-being tests in postterm
      pregnancy.
AB  - BACKGROUND: Although it is well-known that postterm pregnancies are associated
      with the risk of perinatal morbidity and mortality, a comprehensive study on its
      management is lacking. The aim of present study was to determine whether
      ketonuria is associated with abnormal fetal test results in pregnancies >40 weeks
      of gestation. METHODS: In this analytical cross sectional study, a total of 360
      pregnant women with gestational age of >40 weeks were evaluated in two hospitals
      during 2003 - 2004. For each woman, urinary ketones, glucose, pH, proteins, and
      specific gravity were measured by total screen LSG tapes (Rapignost); in
      addition, biophysical profile test was recorded and the amniotic fluid index was
      assessed by ultrasonography. RESULTS: Ketonuria was found in 34 women (9.44%).
      Statistical analyses showed that maternal ketonuria was associated with
      oligohydramnios, abnormal fetal tests, and a significant increase in fetal heart
      rate decelerations. CONCLUSION: Patients with clinically-detectable ketonuria
      have higher risk for abnormal fetal tests in comparison with those without the
      disease.

PMID- 16649358
TI  - The effect of supplemental zinc on the height and weight percentiles of children.
AB  - BACKGROUND: Considering the high incidence of low weight and short stature among
      Iranian children as well as the high prevalence of both mild and moderate types
      of zinc deficiency, this study was conducted among patients who were referred to
      the Pediatric Clinic at Massih Daneshvari Hospital during 1997 - 1999. The aim of
      this study was to determine the effect of zinc supplementation on the children's
      height and weight percentiles. METHODS: Age, sex, and height and weight
      percentiles before and after administration of zinc were determined and recorded.
      The zinc supplement used in this project was in the form of a zinc sulfate
      solution in 0.1% and 0.5% concentrations. The dose was the upper limit of a
      tolerable dose, which was given in three divided doses per day. The serum zinc
      level was measured with the atomic absorption spectrophotometry method. The
      effect of age, sex, and initial serum zinc level on the percentile changes were
      determined. RESULTS: This study was conducted on 42 children with equal
      distribution of gender (21 male and 21 female patients). The mean age was 4.9 +/-
      4.1 years. Means of height and weight were 101.8 +/- 23 cm and 16.5 +/- 8.1 kg,
      respectively. The initial serum zinc level was 85.1 +/- 31.6 microg/dL. The
      duration of zinc administration was 3.2 +/- 2.6 months. The subjects were
      followed for a minimum of one month to a maximum of 10 months. The percentage of
      children with weight and height percentiles below the 50th percentile was reduced
      from 69% to 54% (P < 0.05) and from 50% to 33% (P < 0.01), respectively. Also, it
      was noted that children with low serum zinc levels demonstrated greater
      percentile changes. CONCLUSION: It was concluded that supplemental zinc increases
      height and weight percentiles.

PMID- 16649359
TI  - Prevalence of hepatitis B, hepatitis C, human immunodeficiency virus, and
      syphilis among street children residing in southern Tehran, Iran.
AB  - Street children are among vulnerable people in the world. They are one of the
      main groups in the society who affect the pattern of health. To determine the
      prevalence of hepatitis B, hepatitis C, human immunodeficiency viruses (HIV), and
      syphilis among street children residing in southern Tehran, Iran. In a cross
      sectional study, we selected 102 children aged below 15 years from southern
      Tehran. The selected children had an interview and were examined. From each child
      a blood sample was taken and tested for anti-HIV (ELISA), anti-HCV (ELISA), HBsAg
      (ELISA), anti-HBs, anti-HBc (radioimmunoassay [RIA]), rapid plasma reagin (RPR),
      and fluorescent treponema antibody absorption (FTA-ABS). We studied 39 (38%) boys
      and 63 (62%) girls, including 79 (77%) Afghan and 16 (16%) Iranian children. The
      nationality of 8 children could not be identified. The children were negative for
      syphilis, HIV, and HCV. Nevertheless, 3 of them were positive for HBsAg and 15
      were HBsAb positive (>10 MIU/mL). The majority of street children are immigrants.
      Although these children did not have syphilis, HIV, and HCV, they are at risk of
      HBV.

PMID- 16649360
TI  - Neuroimaging in children with first afebrile seizures: to order or not to order?
AB  - Seizures are common in children and 5% of all medical attendances to accident and
      emergency departments are related to seizures. The role of emergent neuroimaging
      for those children with first afebrile seizure is, however, not well-defined. We
      reviewed medical charts of 125 children who were admitted with a new-onset
      afebrile seizure to the Pediatric Ward of Rasool Akram Hospital and underwent CT
      scan or MRI of the brain. Neuroimaging was performed for 95% (119/125) of these
      children over the first few hours of their arrival to the Emergency Department.
      In 90% (107/119) of them, the result was normal. There was a significant
      relationship between abnormal neuroimaging and focal seizure (P < 0.001), and
      with age under 2 years (P < 0.002). Therefore, it is recommended that CT scan or
      MRI to be performed in children with first afebrile seizure who present with
      focal seizures, abnormal neurologic findings, or age under 2 years.

PMID- 16649361
TI  - Isolated tuberculosis of the talus bone.
AB  - A 7-year-old boy was referred to us with a 3-month history of swelling and pain
      on his left ankle. On laboratory evaluation, he only had an elevated erythrocyte
      sedimentation rate. X-ray showed an extensive lytic lesion of the talus bone.
      Chest roentgenogram was normal. The Mantuex skin test was negative. Histological
      examination of the biopsy tissue showed granuloma and caseating necrosis of
      tuberculosis. Talectomy with 6 months of antituberculous chemotheraphy resulted
      in a good clinical outcome.

PMID- 16649362
TI  - Left renal vein transposition for treatment of the Nutcracker syndrome.
AB  - The nutcracker syndrome refers to compression of the left renal vein between the
      aorta and the superior mesenteric artery, which results in renal vein and left
      gonadal vein varices. Herein, we report our experience with left renal vein
      transposition for treatment of the nutcracker syndrome. To the best of our
      knowledge, this is the first reported case of the left renal vein transposition
      for treatment of the nutcracker syndrome in Iran.

PMID- 16649363
TI  - Selective disappearance of donor-specific antibodies and absence of acute
      rejection after liver transplantation in a patient with a strongly positive
      lymphocyte crossmatch.
AB  - We report on a young female, who received a cadaveric liver transplant from a
      donor who was a zero antigen match, and to whom she has had a strongly positive
      crossmatch. Immediately after transplantation, her panel reactive antibodies
      dropped from 55% to 0%, a value which remained for nearly 3 weeks. She
      subsequently, redeveloped her pretransplant anti-HLA antibodies, though at a
      lower level, with the exception of those specific to the donor HLA antigens. She
      also did not develop any acute rejection episodes during the 6 months of follow
      up.

PMID- 16649364
TI  - L-2-hydroxyglutaric aciduria: a report of six cases and review of the literature.
AB  - L-2-hydroxyglutaric aciduria is a rare and novel autosomal recessive inherited
      neurometabolic disorder. Since its first description by Duran in 1980, less than
      100 cases have so far been reported. Occurring mostly in childhood, it is
      characterized by slowly progressive neurological dysfunction with cerebellar
      ataxia, pyramidal signs, intellectual decline, seizure, and extrapyramidal
      symptoms. MRI scanning is highly characteristic and screening for organic acid (L
      2-hydroxyglutaric acid) in urine, serum, and cerebrospinal fluid is diagnostic.
      We investigated six Iranian children, aged 4, 14, 16, and 16 years, (the last one
      had two affected brothers and both of them died of similar illness at the ages of
      20 and 22), by urinary organic acids assay and MRI scanning with suspicion of
      this rare disorder. Symptoms were suspicious for one of the leukoencephalopathies
      accompanied by macrocephaly. Affected cases were evaluated because of mild to
      moderate psychomotor retardation and regression. Head circumferences were above 2
      standard deviations. Urine levels of L-2-hydroxyglutaric acid were strongly
      increased. MRI scanning of the brain showed hyperintense signal on T2W images of
      the subcortical white matter and basal ganglia in all of them. Because of its
      inheritance pattern (autosomal recessive) and the high rate of consanguineous
      marriages in Iran, the prevalence of this disorder might be high among the
      mentally-handicapped patients, especially those with macrocephaly. Therefore,
      this entity should be considered in the differential diagnosis of mentally
      retarded patients with macrocephaly.

PMID- 16649365
TI  - Recurrence of hemolytic-uremic syndrome following live related renal
      transplantation.
AB  - There is a significant risk of disease recurrence in patients with diarrhea
      negative hemolyticuremic syndrome undergoing renal transplantation. Considering
      the low frequency of hemolyticuremic syndrome among adults with end-stage renal
      disease, only a few reports are available on the outcome of these patients after
      renal transplantation. It has been suggested, though not proven, that living
      related transplant recipients are at increased risk of recurrence of
      hemolyticuremic syndrome. We report a 23-year-old woman with end-stage renal
      disease, owing to postpartum hemolyticuremic syndrome and the recurrence of the
      disease following live related renal transplant. Investigators believe that some
      cases of atypical hemolytic-uremic syndrome are familial and related donors may
      have a genetic susceptibility to develop hemolytic-uremic syndrome. In addition,
      recurrence of hemolytic-uremic syndrome in the allograft is associated with a
      very poor prognosis. Therefore, at present, many clinicians are reluctant to
      recommend live related transplantation in any forms of diarrhea-negative
      hemolytic-uremic syndrome.

PMID- 16649366
TI  - How to manage asymptomatic liver hydatids.

PMID- 16649367
TI  - Photoclinic. Primary alveolar soft part sarcoma of bone.

PMID- 16649368
TI  - Marshall and Warren: the Nobel Prize winners in medicine in 2005.

PMID- 16649369
TI  - Landmine injuries: experience in the West Azarbaijan Province.

PMID- 16649370
TI  - Current treatment of chronic hepatitis B.
AB  - The primary goal of therapy in patients with chronic hepatitis B is suppression
      and long-lasting maintenance of hepatitis B virus DNA to its lowest possible
      level. The threshold of hepatitis B virus DNA level for therapy is > or = 10(5)
      copies/mL for HBeAg-positive patients and > or = 10(4) for those with HBeAg
      negative chronic hepatitis B. Interferon alpha-2b, lamivudine, and adefovir
      dipivoxil are approved by FDA and could all be used as an initial first-line
      therapy in chronic hepatitis B. Adding lamivudine to either conventional
      interferon or peg-interferon did not increase the efficacy. Adding lamivudine to
      adefovir had also no additional effect in compensated patients. Response rate is
      about 30% - 40% with first-line drugs. Peg-interferon, which recently received
      the FDA approval, is associated with an increased response rate. Further long
      term studies are required to use peg-interferon as a widespread first-line
      treatment. Treatment strategy is changing towards using prolonged combination
      therapy with evolving nucleoside analogues with or without an immunomodulatory
      agent, aiming at eradicating covalently closed circular DNA.

PMID- 16649371
TI  - Determination of definitive and intermediate hosts of cercarial dermatitis
      producing agents in northern Iran.
AB  - BACKGROUND: The study concerns the prevalence of avian schistosomes in
      intermediate and definite hosts in Mazandaran Province, northern Iran. METHODS: A
      total of 14190 fresh-water snails belonging to various genera were sampled and
      tested for cercarial emission by lighting and then crushing. During the same
      period, the nasal blood vessels and mesenteric veins of aquatic birds, mainly
      belonging to the Anatidae family, were examined under dissecting microscope for
      detecting adult worms. RESULTS: Forty-seven (0.33%) of examined snails mainly
      Lymnaea gedrosiana, L.palustris, L.stagnalis, and Planorbis planorbis were found
      to be infected with larval stages of Trichobilharzia spp. Adult schistosomes were
      observed in 25 (18.1%) wild waterfowls. The most infected birds were Anas
      platyrhynchos, A.clypeata, and Aythya ferina, respectively. CONCLUSION: Annually
      migration of various species of aquatic birds toward the northern parts of Iran
      and the simultaneous presence of intermediate snails in the water resources of
      this area, combined with long hours of sunshine in the summer months, suggest
      that cercarial dermatitis could be a prominent health problem, especially among
      paddy field workers in this area.

PMID- 16649372
TI  - Subfascial endoscopic perforator vein surgery: the first report from Iran.
AB  - BACKGROUND: Chronic venous stasis ulcers of the leg are still a challenge in
      vascular surgery. Innovation of new surgical techniques using endoscopic
      instruments have ushered in a new era with less complications and better results.
      This study was designed to evaluate the safety and long-term outcomes of this
      technique for the first time in Iran. METHODS: Subfascial endoscopic perforator
      vein surgery was performed on 10 legs in 8 patients who had signs of chronic
      venous insufficiency (between September 2001 and September 2003). Patients were
      followed up for a mean of period 12.5 months. RESULTS: The operations were
      performed successfully in all patients. No serious complications occurred
      intraoperatively. There was no mortality or significant morbidity. Complete
      healing of skin ulcers was observed in 5 active and 2 healed ulcers in less than
      12 weeks. There were 2 recurrences after 4 and 27 months, respectively.
      CONCLUSION: Subfascial endoscopic perforator surgery is a safe procedure for the
      treatment of venous stasis ulcers. Rapid ulcer healing can be expected in
      selected patients.

PMID- 16649373
TI  - Risk factors for neural tube defects: a study at university-affiliated hospitals
      in Tehran.
AB  - BACKGROUND: Neural tube defects have a complex and imperfectly understood
      etiology involving both genetic and environmental factors. In this case-control
      study, we tried to determine the association of known risk factors for neural
      tube defects in patients referred to university-affiliated hospitals with
      neurosurgical services in the city of Tehran. METHODS: Risk factors were assessed
      in-person through interviews with infants' mothers. We found 192 neural tube
      defect cases. One hundred and ninety-three apparently normal babies were randomly
      selected from the same hospitals to serve as control cases. RESULTS: Maternal age
      of less than 18 years (P = 0.02), female sex of the child (P = 0.01), birth in
      spring and summer seasons (P = 0.001), history of not using folic acid (P =
      0.001), less than 5 prenatal visits (P = 0.001), and poverty (P = 0.02) were the
      most important risk factors for neural tube defects. Logistic regression analysis
      of these risk factors confirmed these correlations. A negative history of
      consuming folic acid had the most significant statistical correlation with these
      malformations. CONCLUSION: Poor quality diets were an important environmental
      risk factor in this study.

PMID- 16649374
TI  - Arteriovenous fistula thrombosis in patients on regular hemodialysis: a report of
      171 patients.
AB  - BACKGROUND: Fistula thrombosis in patients on maintenance hemodialysis is an
      important morbidity factor. Arterial or venous thrombotic events have been
      described as complications in patients on regular hemodialysis. This study was
      designed to evaluate the risk factors for arteriovenous fistula thrombosis.
      METHODS: One hundred and seventy-one patients with arteriovenous fistula on
      maintenance hemodialysis were studied prospectively during a period of 14 months
      for any episode of arteriovenous fistula thrombosis, after anticardiolipin
      antibodies were assayed by ELISA. Other risk factors for thrombosis such as the
      presence of diabetes or hypertension, the use of erythropoietin (rhEPO), fistula
      site, gender, age, ultrafiltration, hypotension during dialysis, and the number
      of dialysis visits in a week were assessed. RESULTS: Fifty-six percent of
      patients had IgG-anticardiolipin antibodies > or = 10GPL, which was significantly
      correlated with dialysis duration (23.18 +/- 24.56 months in patients with
      anticardiolipin antibodies < or = 10GPL vs. 37.73 +/- 36.35 months in patients
      with 20 < or = IgG-anticardiolipin antibodies < 40GPL). Within the 14 months of
      follow-up, 36 episodes of arteriovenous fistula thrombosis occurred in 31
      patients (18.1%). Considering anticardiolipin antibodies and other risk factors
      in a Cox proportional hazard model, only fistula site (P = 0.021, RR = 2.48, Cl =
      1.14 - 5.37) and erythropoietin (Eprex) use (P = 0.021, RR = 10.92, Cl = 1.43 -
      83.02) seemed to have an influence on fistula patency. According to fistula site,
      the survival of brachiocephalic fistulas were significantly (P = 0.007) better
      than radiocephalic ones (1- and 3-year survival were 95% and 87% for upper, and
      88% and 72% for lower ones, respectively). CONCLUSION: Although the incidence of
      the anticardiolipin antibody was high in our patients, in the presence of other
      risk factors for thrombosis, we found no correlation between IgG-anticardiolipin
      antibodies and arteriovenous fistula thrombosis. Instead, erythropoietin (Eprex)
      use and fistula site seem to have an important role in the correlation between
      IgG-anticardiolipin antibodies and arteriovenous fistula thrombosis.

PMID- 16649375
TI  - The effect of topical application of human milk, ethyl alcohol 96%, and silver
      sulfadiazine on umbilical cord separation time in newborn infants.
AB  - BACKGROUND: Several agents have been used for neonatal umbilical cord care, but
      we did not find any study evaluating the effect of human milk on umbilical cord
      separation time. The purpose of this study was to compare the effect of topical
      application of human milk, ethyl alcohol 96%, and silver sulfadiazine on
      umbilical cord separation time in newborn infants. This study was undertaken
      place at a primary-level newborn nursery at a university teaching hospital and a
      private hospital. Of 373 singleton near- to full-term newborns enrolled in the
      study, 312 completed the study. METHODS: Newborns from birth were randomized to
      either: 1) mother's milk group, 2) alcohol group, 3) silver sulfadiazine group,
      and 4) control (no treatment) group. Mother's milk for group 1, ethyl alcohol for
      group 2, and silver sulfadiazine ointment for group 3 were applied to the
      umbilical stump three hours after birth and continued every eight hours until two
      days after umbilical cord separation. The time to umbilical cord separation and
      any discomfort such as infection, hemorrhage, and granuloma formation were
      reported by mothers. Nothing was applied to the umbilical stump of the control
      group and they received dry cord care only. RESULTS: It was observed a
      significant difference in the mean cord separation time among the four group. No
      significant complications were observed in any group. CONCLUSION: Breast milk
      could be substituted for other topical agents for umbilical cord care, but a
      multicenter study is required in order to advise it for routine umbilical cord
      care.

PMID- 16649376
TI  - Burden of abortion: induced and spontaneous.
AB  - BACKGROUND: Abortion is a public health concern because of its impact on maternal
      morbidity and mortality. Each year, about 79 million unintended pregnancies,
      excluding miscarriage, occur worldwide. More than half of these unintended
      pregnancies end in abortion. The purpose of this study was to determine the ever
      event incidence of abortion (spontaneous and induced) and some related factors in
      a population-based sample of reproductive age women. METHODS: From July 2003
      through January 2004, 2470 women were included in the study through multistage
      random sampling and were interviewed. Data were collected using a checklist with
      questions about demographics and specific items regarding abortion history.
      Information about age, literacy, gravidity, marriage age, abortion, type of
      abortion, family history of abortion, history of family marriage, smoking, drug
      use, alcohol use, coffee intake, and incidence of abortion during the previous
      year were recorded. Statistical analysis included Student's t-test, Chi-square,
      ANOVA, and logistic regression using SPSS software. RESULTS: Out of the 2,470
      women in the study, 775 (45.7%), had at least one abortion in their lives. Of the
      women who had an abortion, 20.6% reported induced abortion and 74.2% reported
      spontaneous abortion. Forty-one point four percent of women aged 45 years and
      older had at least one abortion in their lifetime. Fifty-one (2.1%) women had a
      history of abortion during the previous year; the largest proportion was 5.4% for
      the age group 15 - 24 years. The most common method of induced abortion in the
      previous year was dilatation and curettage (42 to 67%). In multivariate analysis,
      household number, coffee consumption, gravidity, smoking, and history of abortion
      in the family were the most important factors related to abortion in the
      different age groups of women. CONCLUSION: This study shows that the occurrence
      of at least one abortion in the life of women in our setting is high and varies
      by age group. There is a need for expanded comprehensive sexual and reproductive
      health services, and more education and accessibility of contraception methods.

PMID- 16649377
TI  - Determination of p53 expression in basal cell carcinoma tissues and adjacent
      nontumoral epidermis from sun-exposed areas of the head and neck.
AB  - BACKGROUND: This study determines the expression of P53 protein and the intensity
      of immunoreactivity in basal cell carcinoma in comparison with the adjacent
      nontumoral epidermis in sun-exposed areas of the head and neck regions. The mean
      age of immunoreactivity in tumoral and adjacent nontumoral epidermis is also
      determined. METHODS: This descriptive-analytical study was performed
      retrospectively over a 5-year period on 150 basal cell carcinoma cases in the
      Pathology Department of Alzahra Hospital in Isfahan. Proper quality paraffin
      blocks were chosen for immunohistochemical staining for P53 through the
      immunoperoxidase method. The intensity of immunoreactivity was graded. The age of
      the patients was also recorded. RESULTS: Positive P53 immunoreactivity was
      observed in 123 basal cell carcinoma tissues (82%) and in 117 adjacent nontumoral
      epidermis (78%) (P = 0.38). The frequency of severe immunoreactivity in tumoral
      tissue and in adjacent nontumoral epidermis was 46% and 32%, respectively (P =
      0.046). The mean age of P53 expression was 66.2 years for tumoral tissue and 66.1
      years for nontumoral epidermis. The mean age of those who did not express P53 was
      52.6 and 55.9 years for the tumoral and nontumoral epidermis, respectively (P <
      0.001). CONCLUSION: No significant difference was detected between P53
      immunoreactivity in tumoral tissue and adjacent nontumoral epidermis. Intensity
      of P53 immunoreactivity was greater in tumoral specimens. Comparison of mean ages
      showed a significant difference between P53-expressing and non-P53-expressing
      groups.

PMID- 16649378
TI  - Treatment of infected pseudoaneurysm in drug abusers: ligation or reconstruction?
AB  - BACKGROUND: Recently, there has been an increase in the incidence of major
      vascular complications such as infected pseudoaneurysm due to intravenous drug
      use. OBJECTIVE: For better understanding of the existing controversies regarding
      the optimal surgical management of infected pseudoaneurysm, the present study was
      conducted. METHODS: Medical charts of 36 consecutive patients who underwent
      surgery in Taleghani Hospital, Tehran, Iran from 1996 through 2003, were
      retrospectively analyzed. RESULTS: We studied the hospital records of 33 cases;
      two patients had bilaterally infected pseudoaneurysms and one underwent an
      emergency reoperation. The total number of operations was 36. Eleven cases
      (30.5%) underwent ileofemoral reconstruction and 25 (69.5%) arteries were
      ligated. All patients presented with infected femoral or brachial pseudoaneurysms
      due to intravenous drug abuse. Postoperatively, there was no hemorrhage, vascular
      thrombosis, amputation, or mortality. Three cases (8%) had incisional infections
      (2 [18%] after reconstruction and 1 [4%] after ligation operation) and 7 patients
      (19%) had claudication (all after ligation). CONCLUSION: Ligation is the optimal
      management for infected pseudoaneurysm, because it is easy, cost-effective, and
      safe. Reconstruction is not recommended, because of an extended infection at the
      location of pseudoaneurysm and at the artificial graft site.

PMID- 16649379
TI  - Increased activation and expansion of a CD57+ subset within peripheral CD8+ T
      lymphocytes in Mycobacterium tuberculosis-infected patients.
AB  - BACKGROUND: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte
      responses restrict the spread of extracellular pathogens by limiting
      M.tuberculosis replication. Alterations in cytolytic function, inappropriate
      maturation/differentiation, and limited proliferation could reduce their ability
      to control M.tuberculosis replication. METHODS: In an attempt to further
      characterize the immune responses during M.tuberculosis infection, we enumerated
      gamma-delta and alpha-beta receptor-bearing T cells expressing CD8 or CD4
      phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T
      lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant
      patients) and 20 control subjects, using flowcytometry. RESULTS: We found that
      the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis
      patients compared to multidrug resistant and control subjects (P < 0.003). Also,
      we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed
      patients was defined by increased surface expression of CD57 as compared to the
      two other settings (P < 0.002). This increase was more profound in patients with
      an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that
      this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed
      in the percentages of CD8+CD57+ T cells between the different settings. Moreover,
      the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in
      multidrug resistant patients when compared to newly-diagnosed subjects (P <
      0.002), but not to the control subjects. In contrast, the frequency of CD28+
      marker on CD4+ T cells was higher in the setting of multidrug resistant compared
      with those of new cases (P < 0.0001). No significant changes were observed in
      percentages of gamma-delta receptor-bearing T cells between different groups.
      CONCLUSION: We suggest that the increase in the proportion of CD57+ within CD8+ T
      cells in newly-diagnosed patients results from M.tuberculosis antigenic
      stimulation, which is a hallmark of many infections and that the protracted
      accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation
      phenotype.

PMID- 16649380
TI  - Physical growth standards in six- to twelve-year-old children in Mashhad, Iran.
AB  - BACKGROUND: Growth is an increase in the physical dimensions and its result is a
      quantitative change in the body. Development is a progressive increase in the
      skills and functional capacity of a child and its result is a qualitative change
      in a child's function. METHODS: This investigation was a descriptive,
      decompositive, and observative study, which was performed on a random group of
      5,378, 6- to 12-year-old children in 45 schools in the urban population of
      Mashhad, Khorasan Province, Iran. RESULTS: The height and weight averages of the
      studied children were more than the averages of Nelson's Textbook of Pediatrics.
      However, as age increased, the height and weight averages of the studied children
      became less than the averages of Nelson. CONCLUSION: To accelerate children's
      physical growth, we should closely follow up on factors which could fortify
      children and affect their growth.

PMID- 16649381
TI  - Generation of IL-8 and TNF-alpha in platelet concentrates during storage.
AB  - BACKGROUND: Platelet transfusion is accompanied by febrile nonhemolytic
      transfusion reactions. The generation of cytokines (like IL-1 beta, IL-6, IL-8,
      and TNF-alpha) in platelet concentrates by white cells is suggested to be
      responsible for febrile nonhemolytic transfusion reactions. The number of white
      cells in the platelet concentrates is crucial to cytokine generation. METHODS:
      This study was performed to determine whether WBC reduction in platelet
      concentrates by prestorage leukodepletion filters or inactivation by gamma
      radiation reduced the levels of these cytokines during storage for 3 days. Each
      of the platelet concentrates (n = 54) was prepared from a single random donor by
      platelet-rich plasma. This was then divided into four groups: 1) unfiltered,
      nonirradiated random-donner platelet concentrates (n = 13); 2) unfiltered, gamma
      irradiated random-donner platelet concentrates (n = 16); 3) filtered,
      nonirradiated random-donner platelet concentrates (n = 14); and 4) filtered,
      gamma-irradiated random-donner platelet concentrates (n = 11). Cytokine levels in
      platelet concentrates supernatants were measured by ELISA kits according to the
      manufacturer's recommendations. RESULTS: Our results showed that IL-8 was
      detected in unfiltered, nonirradiated, and gamma-irradiated random-donner
      platelet concentrates but not in the filtered random-donner platelet
      concentrates. TNF-alpha was only detected in unfiltered, nonirradiated units.
      Compared with unfiltered platelet concentrates, prestorage filtration prevented a
      rise in the IL-8 and TNF-alpha on day 3 of storage. The concentration of IL-1
      beta was lower than the minimum concentration value of the kit used for this
      purpose. IL-6 was detected only in 7 units of all filtered platelet concentrates
      on day 3. CONCLUSION: These data indicate that gamma irradiation can not prevent
      generation of IL-8 in platelet concentrates during storage, but prestorage
      leukoreduction of platelet concentrates can prevent accumulation of IL-6, IL-8,
      and TNF-alpha during storage.

PMID- 16649382
TI  - Epidemiology of familial and sporadic restless legs syndrome in Iran.
AB  - Restless legs syndrome is one of the most common sleep and movement disorders.
      For lack of sufficient information on this syndrome in Iran, this study was
      conducted at Alzahra Hospital, Isfahan, Central Iran, to determine the
      epidemiology of idiopathic, familial and sporadic forms of the syndrome. From
      September 1999 to April 2003, 61 patients in two groups were selected. A
      questionnaire with emphasis on sleep history and neurological history was
      completed and a thorough physical examination was performed for each patient.
      Familial and sporadic groups had mean +/- SD ages of 22 +/- 2.1 and 41 +/- 3.2
      years, respectively (P < 0.05). Female to male ratio was 2:1. The mean +/- SD
      ages for women and men were 31 +/- 5.3 and 42 +/- 6.1 years (P < 0.05),
      respectively. Our findings support the current opinion that restless legs
      syndrome should be divided into the early-onset disease with a clear genetic
      component and the late-onset disease with an unclear etiology.

PMID- 16649383
TI  - Becker's nevus with ipsilateral breast hypoplasia: a case report and review of
      literature.
AB  - Specific cutaneous associations in patients with Becker's nevus have been
      reported. We present a patient with typical clinical and histopathological
      features clearly consistent with Becker's nevus associated with ipsilateral
      breast hypoplasia. The changes were distinct and could be separated from smooth
      muscle hamartoma. We include clinical and histological illustrations of our case.

PMID- 16649384
TI  - Abdominal pain due to lead-contaminated opium: a new source of inorganic lead
      poisoning in Iran.
AB  - Although the incidence of occupational and adult lead poisoning has declined, the
      problem still exists. We encountered three patients with lead poisoning in Iran,
      all of whom associated with presented with diffuse abdominal pain, which was at
      times colicky in nature, anemia, constipation, nausea, vomiting, and slightly
      abnormal liver biochemistries. A history of opium ingestion was present in each
      of these patients. None of the patients reported known occupational exposure to
      toxins. Diagnoses of lead poisoning were confirmed through the detection of
      elevated blood lead levels. The cause of lead poisoning was attributed to the
      ingestion of contaminated opium. Opium adulterated with lead had not been
      previously recognized as a source of lead poisoning in Iran. It is, therefore,
      pointed out that lead poisoning should be considered as a differential diagnosis
      for acute abdominal colic of unclear cause in patients with opium addiction.

PMID- 16649385
TI  - Delusion of oral parasitosis in a patient with major depressive disorder.
AB  - Delusion of parasitosis is a rare condition in which the patient has a strong
      conviction that he or she is infested by small organisms. The condition may exist
      as an isolated phenomenon, or may occur in association with other psychiatric
      syndromes. We report a single case of a rare form of this phenomenon. A middle
      aged woman who met forth edition of diagnostic and statistical manual of mental
      disorders criteria for major depressive disorder with psychotic features is
      described. She had delusions of oral parasitosis. She felt lizards and small
      organisms in her mouth. To the best of our knowledge, there has been only one
      previous report of delusions of oral parasitosis to date. We discuss the
      interesting aspects of this case.

PMID- 16649386
TI  - Hereditary hemochromatosis: a rare disease in Iran.
AB  - Hereditary hemochromatosis is a common cause of chronic liver disease in western
      countries. No report of this disease has appeared from Iran and the few studies
      which have focused on chronic liver disease have failed to identify a single case
      of hemochromatosis. In this report, we present the first case of hereditary
      hemochromatosis during our 25 years of gastroenterology practice in Iran.

PMID- 16649387
TI  - Photoclinic. Rhinosporidiosis.

PMID- 16649388
TI  - Dr. Johan Louis Schlimmer (1819 - 1881): the eminent professor of modern medicine
      at Dar Al-Fonun School.

PMID- 16649389
TI  - Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B.

PMID- 16649390
TI  - Current status of medical journalism in Iran.

PMID- 16649391
TI  - [A multidisciplinary approach is necessary in the neonatal withdrawal syndrome].
AB  - Two baby boys, born of mothers that were abusing drugs, were restless and
      hypertonic, typical symptoms of the neonatal withdrawal syndrome. The symptoms
      disappeared during treatment with phenobarbital and methadone. The children were
      then placed in a foster home. Symptoms of the neonatal withdrawal syndrome are
      excitation of the central nervous system, the gastrointestinal tract and the
      respiratory tract. For both legal and medical reasons it is essential to test the
      urine of the neonate for drugs. The Finnegan score is a useful tool to decide
      whether medical treatment is indicated. Medical treatment consists of the
      administration of phenobarbital and or methadone. The Child Protection Agency of
      the Ministry of Justice is notified of the child's birth. If parents that are
      abusing drugs have been shown not to be able to look after their children, they
      are limited in their right to parenthood.

PMID- 16649392
TI  - [First trimester medical abortion: a good method that is seldom used in The
      Netherlands].
AB  - A majority of Dutch women present their request for termination of pregnancy very
      early after their missed period. For these women, medical abortion with
      mifepriston and misoprostol is a good option. The method is only rarely used in
      The Netherlands. A change in attitude of the care-providers, dissemination of
      information to women and new legislation is needed to increase the use of this
      non-invasive treatment, which has proven to be safe up to 9 weeks in the home
      situation.

PMID- 16649393
TI  - [The role of trastuzumab in mammary carcinoma in The Netherlands].
AB  - Trastuzumab is the first humanised monoclonal antibody to demonstrate activity in
      patients with HER2/neu-positive breast cancer. It has taken almost 20 years of
      research from the first description of HER2/neu as an unfavourable prognostic
      factor until the development of a clinically applicable antibody that has now
      shown convincing activity in the adjuvant setting: not only progression-free
      survival (HR: 0.48-0.54) but also distant disease-free survival (HR: 0.47-0.49)
      and overall survival (HR: 0.41-0.67) were improved after four years. It is a good
      thing, therefore, that shortly after the publication of these striking results,
      the specialists concerned have designated trastuzumab in combination with
      chemotherapy as the standard adjuvant treatment for patients with HER2/neu
      positive rumours. This decision anticipates the formal registration for this
      indication and the rules for reimbursement. Nevertheless, this effective form of
      treatment may not be withheld from the patients concerned in the Netherlands
      merely on formal grounds, since there can be no doubt as to the indication.

PMID- 16649394
TI  - [Effects and costs of adjuvant chemotherapy for operable lymph node positive
      breast cancer with HER2/neu overexpression].
AB  - Newer forms ofadjuvant chemotherapy can considerably improve the prognosis for
      breast cancer. The benefits that can be achieved are particularly high for young
      women (< 50 years) with an unfavourable risk profile (tumour-positive axilliary
      nodes). The recent application of taxans and trastuzumab has sharply increased
      the costs of an adjuvant treatment for high-risk mammary breast carcinoma. The
      cost increase can especially be attributed to trastuzumab. The additional costs
      of cytostatics (10,079 Euro per life-year gained) appear to be justified if the
      following is taken into account: women under the age of 50 years still have a
      life expectancy of approximately 33 years, many have socially relevant positions,
      and that cure also prevents such things as absence through illness and inability
      to work as well as expensive palliative care. The pharmaceutical industry spends
      approximately the same amount on research and innovation as it does on
      advertising. By reducing marketing costs, there will be more room to lessen the
      costs of new and socially relevant medications. Ultimately, the pressing question
      remains on why the Dutch government does not fully compensate hospitals in the
      Netherlands for the introduction of new, potentially life-saving medications. At
      present, a substantial percentage of the costs has to be paid by the hospitals
      themselves out of the regular hospital budget, which is not meant for this. This
      is happening at the expense of other care to an increasing extent.

PMID- 16649395
TI  - [Surgical treatment of rectal prolapse].
AB  - Rectal prolapse must be distinguished from anal prolapse or mucosal prolapse
      since the treatment differs. The only effective treatment for rectal prolapse is
      surgery. The fact that rectal prolapse causes severe disability and that the
      morbidity of the current surgical treatment is low justifies surgery even at
      advanced age. Moreover, the success rate is high. Ventral rectopexy seems to be
      the surgical technique of choice on the grounds of the anatomical advantages
      (preservation of rectal innervation and lifting of the middle compartment) and
      the results (low recurrence rates and reduction of constipation). The
      laparoscopic approach is just as effective as an open procedure and results in
      less morbidity, quicker recovery and lower medical costs.

PMID- 16649396
TI  - [A request for caesarean section without a medical indication should ultimately
      be granted].
AB  - A request for the performance of an elective caesarean section should be
      discussed openly and the arguments pro and con clearly explained. If the woman
      persists in her request, it would seem advisable to consent. Respect for the
      'intuition' of a pregnant woman who is not motivated in favour of a vaginal
      delivery can prevent the delivery from ending in a secondary caesarean that will
      be perceived as an extremely traumatic experience.

PMID- 16649397
TI  - [No caesarean section on demand without a proper indication].
AB  - The risk/benefit ratio of caesarean section versus vaginal birth does not justify
      performing the operation solely on demand of the woman without a medical
      indication. Underlying fear of childbirth should be addressed by other means
      rather than simply performing the operation. These considerations should not be
      outweighed by women's freedom to decide.

PMID- 16649398
TI  - [Diagnostic image (169). A man with a painful swelling on the hand].
AB  - A 29-year-old man presented with a painful swelling on his right hand, which was
      caused by a carpal boss on the second and third carpometacarpal joint.

PMID- 16649399
TI  - [Centralisation of pancreatic resection: a systematic review and evaluation in
      the Netherlands].
AB  - OBJECTIVE: To analyse the volume-outcome effect of pancreatic surgery by means of
      a systematic review, and to determine the effect of the ongoing plea for
      centralisation of pylorus-preserving pancreaticoduodenectomy in the Netherlands.
      DESIGN: Systematic review and retrospective evaluation. METHOD: A systematic
      search for studies comparing hospital mortality rates after pancreatic resection
      in high- and low-volume hospitals was conducted. The studies were independently
      assessed regarding design, inclusion criteria, threshold value for high and low
      volume and primary hospital mortality outcome. Data were obtained from the Dutch
      nation-wide registry on the mortality outcome of pancreaticoduodenectomy in 1994
      2003. Hospitals were divided into 4 categories based on the number of
      pancreaticoduodenectomies performed. The effect of the ongoing plea for
      centralisation was analysed. RESULTS: Twelve observational studies comprising a
      total of 19,688 patients were included. Because the studies were too
      heterogeneous to allow a meta-analysis, a qualitative analysis was performed. The
      relative risk of dying in a high-volume hospital compared with a low-volume
      hospital was between 0.07 and 0.76 and was inversely proportional to the
      arbitrarily defined volume cut-off values. Various analyses conducted over a to
      year period in the Netherlands reported mortality rates of 14-17% in hospitals
      that performed fewer than 5 pancreaticoduodenectomies per year, compared with
      rates of 0.0-3.50 degrees h in hospitals that performed more than 24
      pancreaticoduodenectomies per year. The percentage of patients undergoing surgery
      in hospitals with a volume less than ro pancreaticoduodenectomies per year was
      57% in 2000-2003 (454/792), compared with 65% (280/428) in 1994-1995. CONCLUSION:
      This systematic review provided evidence of an inverse relationship between
      hospital volume and mortality after pancreaticoduodenectomy and confirmed the
      value of centralisation of this procedure in high-volume hospitals. The 10-year
      long plea of the Dutch surgical community for quality assessment and, if
      necessary, centralisation has not resulted in a reduction in mortality rates
      after pancreatic resection or a change in referral patterns in The Netherlands.

PMID- 16649400
TI  - [A boy with acute cerebellar ataxia without opsoclonus caused by neuroblastoma].
AB  - A 2-year-old boy presented with acute cerebellar ataxia without opsoclonus. The
      ataxia was assumed to be post-viral. After a period of years a neuroblastoma was
      detected. Treatment with a curative intent was successful and consisted of
      metaiodobenzylguanidine I 131, chemotherapy, tumour resection, chemotherapy again
      and follow-up treatment with isotretinoin after irradiation. In the literature, 5
      other children have been described with acute cerebellar ataxia without
      opsoclonus in whom neuroblastoma was detected eventually. The mean age of these
      children at initial presentation was 26 months. The mean time between initial
      presentation and diagnosis ofneuroblastoma or ganglioneuroblastoma was 12 months.
      Urine concentrations of catecholamine metabolites were normal in 5 of the 6 total
      children; concentrations were elevated in 1 child. The tumour was located
      paravertebrally in 5 of the 6 children. Ataxia resolved following resection of
      the neuroblastoma in all patients. Each child with prolonged or recurrent acute
      cerebellar ataxia should be extensively investigated for the presence of
      neuroblastoma, even in the absence of opsoclonus.

PMID- 16649401
TI  - [Interstitial nephritis attributed to treatment with piperacillin-tazobactam and
      with ciprofloxacin].
AB  - A 26-year-old man was treated with piperacillin-tazobactam because of suspected
      cholangitis and a 77-year-old man was given ciprofloxacin because of an infected
      knee-prosthesis. They both developed symptoms of an interstitial nephritis:
      malaise and laboratory deviations. The symptoms disappeared after the antibiotics
      were withdrawn. No other explanation for the renal function disorders could be
      found in either patient. Piperacillin-tazobactam and ciprofloxacin are considered
      to be relatively safe and serious adverse effects are rare. Acute interstitial
      nephritis may, however, occur and its clinical presentation may not be very
      informative. Withdrawal of the culprit usually leads to recovery.

PMID- 16649402
TI  - [Fundamentals of internal medicine].
AB  - The most important diagnostic tools of the internist are the patient history and
      physical examination, after which a plan must be made for further diagnostic
      evaluation and treatment. For this the internist uses clinical reasoning based on
      his or her knowledge of evidence-based medicine and pathobiology. Pathobiology is
      primarily concerned with the question of how something works; evidence-based
      medicine is concerned with whether something works, and if so, how often or how
      much on average. Diseases do not exist in their own right and diagnostic criteria
      are based on consensus. A diagnosis of a 'disease' is based on our observation of
      patients as well as our opinions, whether right or wrong, regarding its cause. It
      is important to distinguish between 'partial causes' and a 'causative
      complement'. As a result of this concept, the biological relevance of a partial
      cause in the development of a disease cannot be derived from the strength of the
      link between it and the disease. Our opinions regarding the cause of disease
      appear to be based on induction. However, induction is not a good foundation from
      which to determine causation. Hypotheses on the cause of disease cannot be
      proved. They can, however, be disproved. Education, training, research and
      patient care all depend on effective communication. Communication is enhanced if
      the thesis is given first and thereafter the arguments. Hence, transfer of
      patient information such as during a morning report should begin with a working
      diagnosis (the 'thesis') and thereafter the findings of patient history, et
      cetera (the 'arguments'). At this time, too little attention is given to these
      branches of clinical reasoning and communication in education and continuing
      education in internal medicine.

PMID- 16649403
TI  - [Migrating pulmonary infiltrates due to a foreign body].

PMID- 16649404
TI  - [The practice guideline 'Heart failure' (first revision) from the Dutch College
      of General Practitioners; a response from the perspective of cardiology].

PMID- 16649405
TI  - [Revised guideline 'Vasectomy' from the Dutch Urological Association].

PMID- 16649406
TI  - [Analysis of stagnation of perinatal mortality in the Czech Republic].
AB  - OBJECTIVE: Analysis of stagnation of perinatal mortality level in the CR in 2000
      2004. DESIGN: Retrospective nationwide epidemiological study of selected
      indicators of perinatal care level. SETTINGS: Institute for the Mother and Child
      Care, Prague, Czech Republic. METHODS: Comparison of selected indicators of
      perinatal care and conditions for such care during years period 2000-2002 and
      2003-2004. RESULTS: Stagnation of perinatal mortality in the Czech republic since
      2000 has been the result of two opposite process. On one side it is the
      continuous increase of newborns of low birth weight as a result of not only
      biological but also demographic and socio-economic risk factors, which create
      unfavorable envirement for provision of perinatal care. On the other side it is
      the improved professional care observed in two areas (prenatal diagnosis of
      congenital malformations and intensive care in newborns of extremely low birth
      weight). During 2003-2004 we were still able to observe odds of improvement of
      professional care against the deteriorating conditions which led to further
      decrease of perinatal mortality by 0.27 per thousand on average. However, there
      is a danger that negative factors will prevail in the near future, because
      reserves for the further improvement of professional care are exhausted and
      analyzed unfavorable factors are continuously on the rise. This could lead to an
      increase of the curently low perinatal mortality level. CONCLUSIONS: Stagnation
      of perinatal mortality in the Czech Republic during the last five years in a
      range of 4.0-4.4 per thousand is a result of two opposite processes. On one side
      it is due to improved level of professional care in prenatal diagnosis, and due
      to centralized intensive care of newborns of extremely low birth weight. However,
      the reserves in those two areas are already exhausted. On the other side there
      are the deteriorating conditions (demographic and social) for such care, which
      are continuously on rise. While the first process has been prevailing until now
      with the resulting minimal decrease of perinatal mortality by 0.4 per thousand,
      there is a danger that the ballance will change in the near future.

PMID- 16649407
TI  - [Ursodeoxycholic acid, S-adenosyl-L-methionine and their combinations in the
      treatment of gestational intrahepatic cholestasis (ICP)].
AB  - SEATING: Department of Obstet. Gynecol., 2nd Medical School Charles University
      and Teaching Hospital Motol, Prague, Institute of Haematology and Blood
      Transfusion Prague, Department of Clin. Bioch. General Teaching Hospital and 1st
      Medical School, Charles University Prague, Czech Republic. AIM OF THE STUDY: To
      compare the efficacy of the monotherapy with ursodeoxycholic acid and S- adenosyl
      L-methione with combined effect of both drugs in the treatment in pregnant women
      with intrahepatic cholestasis of pregnancy. METHODOLOGY: All women with singleton
      pregnancy at <36 weeks of gestation with moderate or severe form of ICP during
      January 1999 to June 2005 were enrolled. All were randomly assigned oral
      ursodeoxycholic acid (UDCA) 3 x 250 mg daily or 500mg S-adenosyl-L-methione
      (SAMe) twice daily in slow running infusion for twelve days ongoing oral 500 mg
      twice daily until delivery. Haematological and biochemical parameters were
      evaluated every week. Intensive monitoring of the fetus with cardiotocography and
      utrasound were accompanied. RESULTS: Of the 78 women enrolled, 25 received SAMe
      and 26 UDCA monotherapy. 27 women received combined therapy with both drugs. At
      enrolment, gestational age, duration of therapy, parity and biochemical
      characteristics were similar in the groups. All types of therapy improve the
      pruritus. The combined therapy and the monotherapy with UDCA led to improving of
      the serum concentrations of bile acids, asparate aminotranspherase, alanine
      aminotranspherase compared with monotherapy with SAMe. The differencies were
      statisticaly significant (p>0.01). The combined therapy led to quicker decrease
      of serum concentrations of bile acids and transaminases compared with UDCA
      monotherapy, however the results are only of borderline statistical significance.
      Gestational age at the time of labor and rate of prematurity were similar in all
      groups. No adverse effects were noted on the fetuses or neonates with either
      therapy. CONCLUSIONS: Ursodeoxycholic acid is effective in improving the
      biochemical parametres during the treatment of ICP. There is probably the
      synergistic effect with S adenosyl-L-methione. Whether the successful treatment
      influence the conditions of the fetus is not clear. The good perinatal outocome
      is probably more due to the precise monitoring of the intrauterine well-being of
      the fetus.

PMID- 16649408
TI  - [Hematological aspects of gestational cholestatic hepatosis (ICP)].
AB  - AIM OF THE STUDY: To assess the changes of hemocoagulative parametres induced by
      ICP from the view of posssible affection of the hemostasis. SEATING: Department
      of Obstet. Gynecol. 2nd Medical School Charles University and Teaching Hospital
      Motol, Prague, Institute of Haematology and Blood Transfusion Prague.
      METHODOLOGY: 20 blood samples of the pregnant with severe signs of ICP underwent
      the precise hemocoagulative analysis. The control group was composed from 12
      women with physiological course of pregnancy comparable in terms of gestational
      week, age and parity. RESULTS: The routine hemocoagulative tests did show any
      statistical significant difference between both groups of examined women. The
      statisticaly significant elevation was found in women with ICP in factor VIII
      (fVIII:C), vWf and in the serum levels of fibrinogen. The elevated levels of
      fibrinogen did not influence the function of platelets and even the analysis of
      fibrinogen itself did not show any significant differences. Clinically assessed
      peripartal blood loss did not deviate from average of loss during the spontaneous
      labor of healthy women. CONCLUSIONS: The changes in hemocoagulative parametres in
      patients with ICP do not increase the risk of thromboembolic events during
      pregnancy and labor. We also did not approve the risk of the higher peripartal
      blood loss in these patinets.

PMID- 16649409
TI  - Doula--a new model of delivery (continuous, nonprofessional care during the
      delivery).
AB  - In the last few years world literature examined advantages related to the
      presence and support of an nonprofessional person (doula) during a delivery.
      Aside from encouraging the husbands to take an active part in the delivery there
      was a rise in popularity of doula's help. The results of frequency questionnaire
      analysis show that in Poland parturients, first and foremost, expect support of a
      professional personnel (midwife, midwifery students).

PMID- 16649410
TI  - [Embryo quality evaluation according to the speed of the first cleavage after
      conventional IVF].
AB  - OBJECTIVE: To evaluate morphological parametres of embryos obtained in the
      process of conventional IVF. DESIGN: A prospective study. SETTING: Centre of
      Assisted Reproduction, Dept. of Obstetrics and Gynecology, Palacky University
      Medical School, Olomouc. METHODS: In the present study 549 embryos developing
      after conventional IVF in the period of 2001-2004 were evaluated. The beginning
      of the mitotic cleavage was assessed within the interval of 24 - 27 hours after
      insemination. The embryos were divided into three groups according to the speed
      of their division as early cleavage (EC) embryos, where two blastomeres were
      present at the time of assessment, break down pronuclei stage (BDPN) where the
      pronuclei had already disappeared, and pronuclei (PN) embryos, where both
      pronuclei were still present. In these groups the degree of fragmentation was
      evaluated on day two of cultivation and embryos were divided into four categories
      as: A - with regular blastomeres, without fragmentation, B - with irregular
      blastomeres or with fragmentation below 30%, C - with fragmentation 30-50%, D -
      with fragmentation above 50%. The speed of further cleavage and average number of
      blastomeres were evaluated on days two and three of cultivation. Statistical
      analysis was preformed in the Palacky University Computer Centre. The chi-square
      test and t test for independent samples were used. RESULTS: EC embryos were found
      in 45.5%, BDPN in 33.5% and PN in 21.0%. EC embryos were less fragmented (p =
      0.000), had more blastomeres at the time of evaluation (p = 0.000) and their
      speed of cleavage was faster (p = 0.000). The cleavage of EC embryos was faster
      in comparisson with the PN group (p = 0.000), but there were no significant
      differences between the EC and BDPN groups on day two of cultivation. On day
      three significant difference was found also between the EC and BDPN groups (p =
      0.000). CONCLUSION: The speed of the first cell cleavage is a useful additional
      criterion for the embryo selection for ET. EC embryos usually have better
      morphology and more blastomeres that the BPDN and PN ones.

PMID- 16649411
TI  - [Inhibin B and intraacrosomal proteins in men from the couples with fertility
      disorders].
AB  - THE AIM: To monitor the basic andrologic and immunologic sperm factors and the
      levels of inhibin B in serum and in seminal plasma in men from the couples with
      infertility disorders. SETTING: Department of Gynecology and Obstetrics, Medical
      School, Charles University and University Hospital, Plzen, Institute of Molecular
      Genetics, AV CR, Prague, Institute of Clinical Immunology and Allergology, LF UK
      a FN, Plzen. METHODS: We used conventional methods for estimation of sperm
      quality according to WHO and we detected the intra-acrosomal proteins by
      monoclonal antibodies (Hs8 and Hs14, immunofluorescent method), spermantibodies
      by direct mixed antiimunoglobulin reaction (MAR) test, and we examined inhibin B
      in serum (< or =400 pg/ml= A) and in seminal plasma (< or = 600 pg/ml= N) by
      ELISA in 355 men aged 21-52 years (o 34 years) with normal levels of FSH, LH and
      testosterone. The control group was created by 56 health sperm donors. RESULTS:
      We found 65% normospermatics in the group of 355 patients, 34.9% men with various
      kind of pathologies. Predominance of spermagglutinating antibodies was found in
      15.77% in IgG, in 19.44% in IgA, in 8.44% in IgA and IgG together. Normal
      intraacrosomal proteins were reached in 74.65% for Hs8, in 20.85% pathologic, in
      86.2% normal findings for Hs14, in 4.23% pathologic. The immunological results in
      control group were completaly negative. Pathological levels of inhibin B in
      seminal plasma was found in 37.2% (152 men), in 25% in serum, and in 5.6% in
      serum and in seminal plasma together. In 54.7% of patients we found physiological
      levels of inhibin B in both biological fluids. We also compared physiological
      109/152 (71.71%), and pathological spermiogrammes 43/152 (28.29%) with abnormal
      levels of inhibin B in seminal plasma, with intraacrosomal proteins to levels of
      inhibin B in serum. Our detailed study shows high interidividual results, which
      must be studied in complex with diagnosis of decreased fertility in man.
      CONCLUSION: Andrologic and immunologic analysis in the group of 355 men showed
      normal parameters of spermiogrammes in 231 patients (65%), in the rest of men the
      immunologic profil was in various parts pathologic. Only 105 men have got
      excellent spermiogrammes. Inhibin B as hormon regulates in back the secretion of
      FSH, and serves as good indicator in male reproductive failures.

PMID- 16649412
TI  - [Prenatal detection of congenital mezoblastic nephroma].
AB  - TYPE OF STUDY: Case report. SETTING: Department of Gynecology and Obstetrics,
      Department of Radiology, Department of Pathology, Department of Medical Genetics,
      Charles University Hospital, Hradec Kralove. METHODS: The autors report a case of
      renal tumor in a fetus at 33 weeks of gestation detected by means of
      ultrasonography and magnetic resonance imaging. The pregnancy course was
      complicated by polyhydramnios. The female infant was born vaginally at 37 weeks
      of gestation. Postnatal nephrectomy confirmed prenatal diagnostic presumption -
      congenital mezoblastic nephroma. At follow-up at 12 months of age, the infant had
      no evidence of the disease. CONCLUSION: Detection of renal tumor in a fetus is
      rare. Congenital mezoblastic nephroma with the favourable prognosis is most
      probable diagnosis. Prenatal detection enables the prevention of complications
      (prematurity prevention, detection of the developing cardial decompensation and
      fetal hydrops) with the planning of labour and postnatal management.

PMID- 16649413
TI  - [Radical parametrectomy in women with invasive cervix cancer after previous
      simple hysterectomy].
AB  - OBJECTIVE: Evaluate technique, indications and limits of surgical procedure in
      the treatment of cervical cancer diagnosed from uterus specimen from simple
      hysterectomy. DESIGN: Retrospective observational study, review of literature.
      SETTINGS: Department of Obstetrics and Gynecology, 1st Medical Faculty and
      General Faculty Hospital, Charles University, Prague, Czech Republic. METHODS:
      Women following radical parametrectomy with upper vaginectomy and pelvic
      lymphadenectomy were enrolled to the study. In all patients unexpected invasive
      cervical cancer was found from the uterus specimen after simple hysterectomy.
      RESULTS: Together 10 patients were enrolled to the study. CIN was the indication
      for primary hysterectomy in all but two patients. There were two operative
      complications, cystostomy in both cases, treated properly during surgery. In the
      specimen from radical procedure residual tumor in parametria was found in 2
      cases, and metastasis to pelvic nodes in 4 cases. There was no postoperative
      complication. Adjuvant radiotherapy was recommended in 4 patients due to positive
      lymph nodes, in one case due to residual tumor in parametria, and in one case for
      both reasons. CONCLUSIONS: Radical parametrectomy with upper vaginectomy and
      pelvic lymphadenectomy should be considered as an alternative solution in
      patients following simple hysterectomy with unexpected finding of invasive
      cervical cancer. Morbidity of the procedure is higher in comparison to standard
      radical hysterectomy, however majority of complications are easy to repair. The
      most significant criteria for patient's selection for surgical approach is a
      depth of invasion to cervical stroma. In our group radical procedure obviated the
      need for radiotherapy in half of the patients.

PMID- 16649414
TI  - [Antibodies against the chlamydial heat shock protein in women with periadnexal
      adhesions].
AB  - OBJECTIVE: To compare and analyze IgG antibodies against chlamydial heat shock
      protein (cHSP60) in the blood serum of women with or without periadnexal
      adhesions in small pelvis. DESIGN: Retrospective study. SETTING: Department of
      Gynaecology and Obstetrics, Masaryk University, Brno, Veterinary Research
      Institute, Brno, Department of Clinical Microbiology, Faculty Hospital Brno.
      METHODS: IgG antibodies against cHSP60 in the blood serum were detected by means
      of recombinant enzyme immunoanalysis ("cHSP60 - IgG - rELISA medac"). The
      presence of antibodies was expressed as +, ++ or +++ pozitive. Laparoscopy
      according to a standard procedure was performed in 76 women (age 28 +/- 43 years)
      from couples with fertility disorders treated in the Centre of Reproductive
      Medicine, Department of Gynaecology and Obstetrics. Chi-square test (programme
      Statcalc - EpiInfo 6) and calculation of OR value were used for statistical
      analysis. RESULTS: Twenty-four women (31.6%) had normal finding in small pelvis.
      Periadnexal adhesions were detected in 43 (56.6%) patients, hydrosalpinx in 13
      cases (17.1%), endometriosis in 27 (35.5%) patients and uterine myomas in 11
      (145%) women. In the group of 33 women without periadnexal adhesions cHSP-60
      antibodies were pozitive in 3 women (9.1%), in 43 women with periadnexal
      adhesions were pozitive in 17 cases (39.5%). In 13 patients with hydrosalpinx
      cHSP-60 antibodies were pozitive in 61.5%. In patients with periadnexal adhesions
      semiquantitative pozitivity +++ was detected in 8 cases (18.6%), 4 of them with
      hydrosalpinx (30.8%). Statistical analysis found significantly higher presence of
      cHSP-60 antibodies in women with periadnexal adhesions (OR = 654, CI interval =
      1.59 - 37.81, chi-square: p = 0.0028) CONCLUSION: Women with periadnexal
      adhesions have more frequent and stronger pozitivity of IgG antibodies against
      chlamydial heat shock protein cHSP60.

PMID- 16649415
TI  - [Syndrome of persistent low levels of human chorionic gonadotrophin (hCG)].
AB  - OBJECTIVE: To analyze the syndrome of persistent low levels of hCG in terms of
      its etiology, classification, diagnosis, and management. DESIGN: Retrospective
      analysis. SETTING: Center for Trophoblastic Disease in Czech Republic, Institute
      for Care of Mother and Child, Prague, Institute of Postgraduate medical
      education, IPVZ, Prague METHODS: An analysis of the syndrome of persistent low
      levels of hCG recorded in CTN in 29 women in the years 1979-2005 by the
      immunoluminesence method which can quantitatively assess variable levels of hCG
      in blood and urine. A comparison was made of our findings with results of a
      similar studies having been done in England and USA. RESULTS: Persistent low
      levels of hCG (PLL) can be differentiated according to cause. 1. PLL-F False
      positive, also known as Phantom hCG, often caused by heterogenous antibodies. 2.
      PLL-H Of hypophysial origin, mainly in perimenopause and menopause. 3. PLL-Q
      Quiescent with trophoblastic disease in history, of trophoblastic origin. 4. PLL
      U Undetermined, in history without trophoblastic disease, but in the past with
      physiological or pathological pregnancy. Assuming also to be of trophoblastic
      origin. All types of PLL lead in practice to the wrong diagnosis of trophoblastic
      disease and to a high percentage (40-80%) of needless chemotherapy and
      operations. In no case of PLL did chemotherapy or operations have an effect on
      PLL and thus are contraindicated. PLL-Q and PLL-U require continuous clinical and
      laboratory monitoring and repeated examinations with sophisticated visualization
      methods. The percentage of developing malignant trophoblastic tumors after PLL-Q
      and PLL-U is unclear. Extreme incidence was established in 7-25%. PLL-Q and PLL-U
      are considered as a marker of persistent trophoblastic invasion. Its detection by
      visualization methods in any organ localization before it turns into a limited
      solid tumor is excluded by it microscopic dissociative structure. CONCLUSION: The
      syndrome of persistent low levels of hCG (PLL) lately affects all gynecological
      and obstetrical workplaces. According to cause it can be divided into: 1. PLL
      false positive, 2. PLL of hypophysial origin, 3.PLL quiescent with trophoblastic
      disease in the history, 4. PLL undetermined, in history without trophoblastic
      disease. In the last two items mentioned above we assume to be of trophoblastic
      origin. Their morphological base is persistent trophoblastic invasion. The
      syndrome of PLL often leads to the wrong diagnosis of trophoblastic disease and
      to needless chemotherapy and operations. In this work was described the diagnosis
      of PLL, its classification, cause, and management. The percentage of PLL turned
      into malignant trophoblastic disease is unknown and ranges from 7-25% and
      requires monitoring in an accredited, national center for trophoblastic disease.

PMID- 16649416
TI  - [New method for detection of nonpalpable breast cancer].
AB  - OBJECTIVE: The objective of the study was to evaluate the feasibility of radio
      guided occult lesion localization (ROLL) in the cases of nonpalpable breast
      cancers with sentinel lymph node biopsy. DESIGN: Prospective clinical study
      SETTING: Department of Gynecology and Obstetrics, 2nd Medical Faculty and
      Teaching Hospital, Praha METHODS: Thirty-eight patients with nonpalpable breast
      cancer diagnosed by core cut biopsy underwent an injection of the
      radiopharmaceutical 18-20 hours before surgery. The dose of the
      radiopharmaceutical was 45 MBg into tumor and 15 MBg subdermaly. Surgical
      excision of radioactive breast tissue with nonpalpable tumor was carried out
      using the hand held gamma probe and the same technique was performed for biopsy
      of sentinel lymph node. Standard localization technique with hook-wire was
      performed in the control group of fifty-one patients. RESULTS: Radioguided
      surgery of nonpalpable tumor was successful in all cases. Surgical margins were
      clear in all cases, in four cases (10.5%) the margins were only 2 mm. The
      sentinel node was identified in all cases, in 3 patients (7.9%) the sentinel node
      was involved by tumor and axillary lymphadenectomy was performed. Infiltrating
      carcinomas were diagnosed in the "hook-wire" group in 21 cases (41.2%), all with
      clear margins over 3mm. Proportion of margins status between ROLL and hook-wire
      was the same. It seems that the health tissue loss around the tumor is in hook
      wire technique bigger but it requires next study. CONCLUSION: Simultaneous
      performance of ROLL and sentinel node biopsy is useful and practicable methods in
      the management of nonpalpable breast cancer. In comparison to hook-wire,
      radioguided removal allows reduced excision volume and better lesion centering
      within the specimen.

PMID- 16649417
TI  - [Possibilities to use the aromatase inhibitors for the treatment of the uterine
      fibroids].
AB  - OBJECTIVE: Review of the contemporary knowledge about the aromatase P 450 in the
      uterine fibroid cells and about possibilities to use the aromatase inhibitors in
      the treatment of uterine fibroids. DESIGN: Review of the literature. SETTING:
      Obstetrics and Gynecology Department, Regional Hospital Pardubice. CONCLUSION:
      The aromatase P-450 in the uterine fibroid cells has a large effect on the
      autocrinne potentiation of growing this tumor. There is a very probable
      possibility to use the aromatase inhibitors for the treatment of the uterine
      fibroids.

PMID- 16649418
TI  - [Recommendations for hormonal therapy and substitution].

PMID- 16649419
TI  - [Strategic action of the Spanish Society of Nephrology confronting chronic renal
      disease ].

PMID- 16649420
TI  - [The role of the pathologist in nephrology].

PMID- 16649421
TI  - [Minimal doses of drugs in hypertension].

PMID- 16649422
TI  - [Atrial fibrillation in dialysis patients].

PMID- 16649423
TI  - [Clinical trials (III). The publication of the results].

PMID- 16649424
TI  - [Guidelines of the Spanish Society of Nephrology: the kidney and cardiovascular
      disease. Short version].

PMID- 16649425
TI  - [Report of the Andalusian registry of patients with end stage renal disease in
      treatment with peritoneal dialysis: period 1999-2004].

PMID- 16649426
TI  - [Solitary kidney. Study of renal morphology and function in 95 children].
AB  - The aim of the study was to evaluate renal growth and function of solitary kidney
      in paediatric patients. MATERIALS AND METHODS: A prospective study was performed
      in a fifteen years period between 1988 and 2003 in paediatric patients with a
      solitary kidney, in a Children's Hospital. All the following parameters were
      evaluated every year: age, sex, ethiology, elapsed time since the concept of
      solitary kidney was assessed (ET), blood pressure, renal function measured by
      GFR, urinary excretion of solutes, concentration ability and microalbuminuria
      (MA). DMSA was made at the beginning and every five years and renal
      ultrasonography was carried out every two years. Two groups were made depending
      of nephrourologic malformations in the remanent kidney and/or antecedents of
      pyelonephritis: Group I with antecedents of pyelonephritis and/or malformations;
      Group II, nor antecedents of pyelonephritis neither malformations. RESULTS:
      Ninety five patients were evaluated, 69% (n = 66) were males and 31% (n = 29)
      were females, with an age at diagnosis of 3.5 yr (ranged 0.1-17 yrs). ET was 9.2
      yrs (range 1-20 yrs). The ethiology was: Nephrectomy of the contralateral kidney
      39 patients (pts) (41%), renal agenesis (RA) 47 pts (49%) and nonfunctioning
      multicystic displastic kidney (MCDK) 9 pts (9.4%). Functional alterations were
      found in 18 pts (19%), such as MA in 12 pts (12.6%), decreased GRF in 5 pts
      (5.5%) and hypertension in 3 pts (3.2%). It was observed more significant
      functional alterations in the patients of the Group I (58%) versus Group II (9%)
      (p < 0.001). There was in Group II a significant correlation between kidney size
      and GFR (p < 0.01, r = 0.3), and between kidney size and ET (P < 0.05; r = 0.3).
      CONCLUSIONS: Any alteration in the renal function was observed in the 12.6% of
      the children. The most frequent affected parameter of renal damage was MA,
      followed by GFR reduction. Arterial hypertension was not a prominent finding.
      Alterations have been less frequently found in RA and MCDK of the Group II, so
      clinical reviews should be made with a lesser frequency.

PMID- 16649427
TI  - [Serum creatinine and creatinine clearance to estimate renal function in
      essential hypertension].
AB  - The shortcoming of serum creatinine (SCr) as an index of renal function is well
      known, patients can have significantly decreased glomerular filtration rates
      (GFR) with normal range SCr values, making the recognition of renal dysfunction
      more difficult. This study was designed to estimate renal function and the
      prevalence of renal dysfunction in essential hypertensive patients, comparing SCr
      and 4 formulas used to measure the creatinine clearance (CrCl) (the urinary CrCl
      formula, Cockcroft-Gault, MDRD and body surface formula) The study included 721
      essential hypertensive patients, 319 men (44.2%), 402 women (55.8%), mean age
      56.3 +/- 13.9 (53.7 +/- 14.4 vs 58.3 +/- 13.3). In all subjects SCr was measured
      and 24-h urine sample was collected to evaluate CrCl. Creatinine clereance was
      calculated by 4 formulas. Patients were grouped according to age (< 40, 41-65, 65
      75 and > 76) and renal function was classified as normal when SCr < 1.4 in women
      and 1.5 mg/dl in men and CrCl (> 60 ml/m, respectively) within the above written
      formulas. SCr increases with age (1.01 +/- 0.36 vs 1.3 +/- 1.15) and CrCl
      decreases according to the 4 formulas (107.6; 92.8; 74.7 and 57.3 for the urinary
      SCr formula); (117.7; 87.7; 65.9 and 49.5 for the CC formula); (87.4, 74.9, 66.5
      and 61 for the MDRD formula) and (97, 85.3, 71.9 and 57.3 for the body suface
      formula). The 4 formulas are comparable markers of renal function in the overall
      population. With any formula the percentage of patients with impaired renal
      function was much higher than indicated by the plasma creatinine alone (4% for
      SCr) vs 18.3-25.3% (CrCl < 60 ml/m) according to the 4 formulas. This study
      documents the substantial prevalence of abnormal renal function in essential
      hypertension. Estimation of GFR may help to facilitate the early identification
      of patients with renal impairment.

PMID- 16649428
TI  - [A burden questionnaire for caregivers of peritoneal dialysis patients].
AB  - INTRODUCTION: Despite the interest generated by the increasing number of studies
      that measure Quality of Life among patients and caregivers, few of these studies
      measure the caregivers burden in Peritoneal Dialysis (PD). OBJECTIVE: The main
      target of this study was to create a burden measure questionnaire applicable
      amongst caregivers of PD patients. METHODOLOGY:  INCLUSION CRITERIA: 1) Patients
      had to be in PD treatment for more than 3 months; 2) Patients had to receive help
      with the PD treatment from a caregiver. The study was divided into 3 phases: 1st)
      design and use of the initial questionnaire; 2nd) a test-retest on a modified
      scale; and 3rd) to provide the questionnaire-3 to two collaborative centres with
      similar PD programs. Four groups of caregivers were established: A1:23, A2:17,
      B:7 and C:16 caregivers. We applied 5 scales (5): 1--Patient Dependence on
      caregiver, from caregivers' view (D); 2--Complete caregiver burden (CB),
      including 12 items which measure the caregivers' subjective burden, 3--Reduced
      caregiver burden (RB), as the one before but with only 8 items, 4--Repercussions
      on the caregiver (R), which measures objective burden; 5--Specific PD tasks (ST),
      a scale that measures the effort the tasks implied in the PD treatment represent
      for the caregiver. RESULTS: We studied 63 caregivers (table I): mean age: 53.43
      (SD = 12.3); Sex: Females: 86.4%, Males: 13.6%, corresponding to 63 patients:
      mean age: 59.79 (SD = 15.9); Sex: Males: 80.3%, Females: 19.7%. Valuable results
      for reliability, unidimensionality, and discrimination were obtained in the 1st
      and 2nd phases, except for burden scale which was compound of two factors; then
      one of those factors was suppressed. In the 3rd phase, ANOVA did not show any
      differences between centres (table II). Consequently, all caregivers could be
      analysed together. Reliability results for each one of the third phase scales
      (table III) were: D: Cronbach alpha = 0,886; CB: alpha = 0,894; RB: alpha =
      0,857; R: alpha = 0,892; ST: alpha = 0,62. Although the ST scale obtained an
      acceptable reliability, it was suppressed in the 3rd phase due to the low
      correlation with other scales and the fact that it was not applicable to all
      caregivers. Finally, a direct correlation was found between third phase scales
      (table IV): D-RB: r = 0.502, p < or = 0.001; D-R: r = 0.599, p < or = 0.001; RB
      R: r = 0.775, p < or = 0.001. We must headlight that both Burden scales, and the
      Repercussion scale, obtained a direct correlation with the Dependency scale.
      CONCLUSION: A questionnaire has been created to measure burden and repercussions
      on caregivers of peritoneal dialysis patients. It can already be applied, as
      requirements of both reliability and validity are fulfilled. This questionnaire
      can be a useful tool to prevent caregivers' burnout.

PMID- 16649429
TI  - [Late nephrology referral influences on morbidity and mortality of hemodialysis
      patients. A provincial study].
AB  - OBJECTIVE: To evaluate the influence of late referral to nephrology of the
      patients with chronic renal failure in the morbimortality of the patients who
      start hemodialysis. SUBJETS AND METHODS: There were included in the study the
      patients who started hemodialysis (HD) as first form of treatment, and that
      survived at least three months in both hospitals of reference of the province of
      Huesca from january 1990 to december 2001. Patients who started HD after acute
      renal failure were excluded. Clinical and analytical data were determined for
      each patient at the start of HD and during the follow-up. Early (ER) and late
      referral (LR) were defined by the time of first nephrology encounter greather
      than or less than 4 months respectively, before HD initiation. Morbidity analysis
      (using multiple linear regression with rate of days of hospitalization as
      dependent variable) and global and anual during the first three years of follow
      up survival analysis (using Cox proportional hazards regression) were carried
      out. RESULTS: A total of 139 patients (78%) started HD in the ER group and 39
      (22%) in LR group. Mean follow-up was similar in both (ER = 34.43 +/- 25.5
      months; LR = 34.42 +/- 28.37 months). At the start of dialysis LR was associated
      to higher proportion of temporary catheters, lower level of hematocrit and
      albumin, higher comorbidity and higher levels of urea and creatinine. Risk
      factors selected by the model in the morbidity analysis were index of comorbidity
      (CI), late referral, serum albumin, urea reduction ratio (URR) and hematocrit (R2
      = 0.334, F = 16.97, p < 0.005). The final equation of regression was: Rate of
      hospitalization's days = 101.12 + (2.45 x CI) - (12. 11 x LR) - (11.57 x Alb.) -
      (0.43 x PRU) - (0.83 x Hto). Variables selected by Cox's regression model that
      were associated with survival throughout complete follow-up were hematocrit (RR =
      -0,207, CI 95% 0.726-0.910, p < 0.0005), index of comorbidity (RR = 0,265, CI 95%
      1.066-1.594, p = 0.007), PRU (RR = - 0,059, CI 95% 0.893-0.996, p = 0.038) and
      type of dialysis membrane (RR = 0,771, Cl 95% 0.260-0.822, p = 0.007).
      Nevertheless, in successive models fitting after 12, 24 and 36 months of follow
      up the variable LR influenced in an independent way survival first two years,
      losing his significance later. CONCLUSION: In our study patients of the group LR
      presented a worse clinical and metabolic situation at the beginning of the HD.
      Later there was demonstrated in this group a higher long-term morbidity and a
      lower survival the first two years.

PMID- 16649430
TI  - [Development and use of a quality assessment scale specifically constructed for
      the assessment of studies that compare hemodialysis modalities].
AB  - There are currently many hemodialysis modalities that are believed to be superior
      to conventional hemodialysis. In order to compare the effectiveness and security
      of the different hemodialysis techniques a systematic review was carried out.
      Faced with the fact that the scales available mainly focus on study design and
      tend to ignore external validity, a quality scale was specifically developed to
      assess the quality of the studies included in the review. The objective of this
      article is to introduce the quality assessment scale developed and present the
      results of its usability and applicability. The following databases were searched
      in order to identify the studies: MEDLINE, EMBASE, Cochrane, HTA, CRD and others.
      The articles obtained were selected based on previously established
      inclusion/exclusion criteria. The scale covers three issues: general aspects of
      the studies, specific aspects of the studies and patient characteristics. This
      scale allowed for a more accurate classification of the global quality of the
      studies and was reproducible. In general, those studies classified as high
      quality studies received the highest score and those studies classified as low
      quality studies received the lowest scores. The median value was 5,35 (53,5%).
      The intraclass correlation coefficient was 0,96. As a conclusion of this work it
      can be stated that currently available scales have serious limitations for the
      use in studies that compare different hemodialysis modalities and that the use of
      a scale specifically constructed for this purpose provides more accurate
      information on the quality of the evidence which is fundamental to interpret
      results and generate inferences.

PMID- 16649431
TI  - [Cardiac troponin I determination in patients with chronic renal failure].
AB  - OBJECTIVE: The aim of the study was evaluate cardiac troponin I (cTnI)
      determination in patients with chronic renal failure (CRF) and compare with
      creatine kinase-MB isoenzyme (CK-MB and CK-MB/CK). METHODS: We performed a
      retrospective study on patients with CRF with MDRD (modification of diet in renal
      disease study group) < 60 mL/min admitted with suspected myocardial injury by
      history, physical examination and electrocardiography. cTnI measurement was
      assessed at admission with the ACCESS analyzer (Beckman). RESULTS: Acute
      myocardial injury (AMI) was diagnosed in 10% (47/467) patients with cTnI
      determination > 0.05 ng/mL, while the diagnostic was angina in 9% (41/467) and in
      81% (379/467) we finded other diagnostics. In the AMI group, 49% had chest
      discomfort, 43% diabetes and the mortality was 45%, while in the angina group
      were 41%, 32% and 7%, respectively. The sensitivity for cTnI with cut-off value >
      0.5 ng/mL was 70% and specificity 92%. The number of false positives was 31% (20
      patients). DISCUSSION: cTnI is the preferred biomarker for myocardial damage in
      patients with CRF. Other cut-off value could enhance the sensitivity for AMI.

PMID- 16649432
TI  - [Renal transplantation in HIV-infected patients in Spain].
AB  - HIV infection has experienced dramatic improvement in morbidity and mortality
      with the highly active antiretroviral therapy (HAART). This prompted a
      reevaluation of organ-solid transplantation as a treatment option for HIV
      infected patients. Some trials in the United States have shown that one- and 2
      year graft and patient survival is comparable to HIV-negative transplant
      population. In Europe the experience is still scarce. The aim of this study is to
      analyse the outcome and the clinical characteristics of HIV-infected patients who
      received kidney transplantation in Spain in the HAART era. Ten patients were
      transplanted in our country since 2001. Only one patient was black. The main
      cause of end-stage renal disease reported was glomerulonephritis. Six of the
      recipients were coinfected by hepatitis C virus. Inclusion criteria included
      undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression
      consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody
      induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46)
      months, respectively. One recipient lost his graft because of early renal venous
      thrombosis. The remaining patients are functioning graft with mean serum
      creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was
      diagnosed in 4 recipients and was reversed in all cases with antirejection
      treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have
      been stable in excess of 200 cell/microL. None of patients have developed AIDS
      complications. Recipients receiving protease inhibitor-based HAART regimens
      required significant dosing modification to maintain appropriate tacrolimus
      levels. Our results show that renal transplantation can be a safe and effective
      treatment in select HIV-infected patients. Like other series, the acute rejection
      rate was higher than in non-HIV recipients. The reasons of this rejection
      incidence remain unknown.

PMID- 16649433
TI  - [Urea distribution volume calculated by ionic dialysance].
AB  - BACKGROUND: Direct dialysis quantification is considered the gold standard for
      determining urea distribution volume, but it is impractical for routine use. So,
      urea distribution volume in hemodialysis patients is usually estimated from
      anthropometric equations. Ionic dialysance allows to calculate the urea
      distribution volume dividing the Kt obtained by ionic dialysance by the Kt/V
      obtained by a simplified formula. The aim of the present work was to analyse the
      concordance between the ionic dialysance and the direct dialysis quantification
      methods to estimate de urea distribution volume. MATERIAL AND METHODS: In 15
      hemodialysis patients (10 males and 5 females), we have estimated the urea
      distribution volume by the direct dialysis quantification (Vurea), by the
      anthropometrics equations of Watson (VWatson) and Chertow (VChertow) and by the
      ionic dialysance method (VDI). To obtain VDI we have used two simplified Kt/V
      formulas: the monocompartimental and the equilibrated Daugirdas equations (VDIm
      and VDIe respectively). The intermethod variability was assessed by the relative
      difference (absolute difference between VUrea and the other methods, divided by
      the mean). RESULTS: VUrea (26,2 L) was statistically different from theVDIe (30,6
      L, p < 0.01), VWatson 35.2 L (p < 0.001) and VChertow (38 L, p < 0.001). VDIm was
      26.3 L (p = ns). VUrea represents the 42% of the body weight for the males (range
      36 to 49%) and the 33% of the body weight for the female (range 28 to 38%). The
      intermethod variability was high for the VDIe (21.6%), VWatson (37.4%) and
      VChertow (48. 1%), but it was low for the VDIm (9.9%). CONCLUSIONS: Urea
      distribution volume calculated by the ionic dialysance method using the
      monocompartimental Daugirdas Kt/V equation has an acceptable agreement with the
      urea distribution volume calculated by the direct dialysis quantification.
      Anthropometry-based equations overestimate the urea distribution volume in
      hemodialysis patients.

PMID- 16649434
TI  - [Hypersensitivity reaction to systemic corticosteroids in a hemodialysis
      patients].
AB  - Hypersensitivity reactions are a feared complication of hemodialysis considering
      their potential for a serious and eventually fatal course. This association could
      reflect a number of different exposures, including concomitant medications. Like
      this, systemic steroid-induced hypersensitivity reactions do occur, althought
      their incidence is extremely rare. A few reactions related to metylprednisolone
      have been reported in renal transplantation. The diagnosis could be confirmed by
      the patient history and performing skin testing, oral or parenteral challenge or
      by the evidence of specific IgE. We report on a 39-year-old woman undergoing
      dialysis therapy in whom severe bronchospasm was induced by corticosteroids. She
      has a positive systemic reaction on the oral steroid challenge test. A successful
      desensitization regimen for safe administration was achieved. The recognition of
      high-risk subjects and alternative therapeutic approach are critical, mainly in
      the management of patients while receiving corticosteroids or a renal allograft.

PMID- 16649435
TI  - [Giant adrenal myelolipoma: hypertension, renal failure and spontaneous rupture].
AB  - Adrenal myelolipoma is a rare, benign, slow-growing tumor composed of adipose
      tissue and hematopoietic elements. It is usually diagnosed incidentally, although
      there are reports of patients with symptoms and descriptions of retroperitoneal
      hemorrhage due to rupture of large tumors. The condition has been associated with
      obesity, high blood pressure and adrenal dysfunction. We present a patient with
      retroperitoneal hemorrhage due to spontaneous rupture of a myelolipoma,
      hypertension, and renal failure secondary to nephroangiosclerosis.

PMID- 16649436
TI  - [Pasteurella multocida and Candida albicans peritonitis].
AB  - Peritonitis is a well-known complication of peritoneal dialysis (PD) treatment.
      Repetitive episodes may induce an irreversible damage of the peritoneal membrane
      and are a frequent cause of PD drop-out. The great majority of the episodes are
      due to Staphylococci, Streptococci or gram- negative organisms. Unusual organisms
      have been reported, specially in immunosuppressed hosts. Few cases of Pasteurella
      Multocida (PM) have been described in PD patients. To our knowledge, we describe
      the first case preceding a Candida Albicans (CA) peritonitis. A review of the
      literature of PM peritonitis and the relation between these two microorganisms is
      discussed.

PMID- 16649437
TI  - [Pleuro-pericardial effusion as the initial manifestation of Wegener's
      granulomatosis].

PMID- 16649438
TI  - [Lupus nephritis, mycophenolate, and cytomegalovirus infection].

PMID- 16649439
TI  - [Treatment with low doses of intravenous iron does not modify hemoglobin nor the
      erythropoietin dosage].

PMID- 16649440
TI  - [Plasmapheresis in amiodarone-induced hyperthyroidism].

PMID- 16649441
TI  - [Hemolytic-uremic syndrome, low C-3 and positive ANCA].

PMID- 16649442
TI  - [Blood pressure elevation in obese descendants of parents with essential arterial
      hypertension and its relation to the renin-angiotensin axis, C-reactive protein,
      and saline taste sensitivity].

PMID- 16649443
TI  - [The dialysis and transplantation report of the Spanish Neurology Society and the
      autonomous community registries].

PMID- 16649444
TI  - Antiphospholipid antibodies in medical practice: a review.
AB  - BACKGROUND: Antiphospholipid antibodies are autoantibodies that have been
      associated with . thrombosis and recurrent foetal loss. The purpose of this
      review is to highlight the history of these antibodies, their epidemiology, to
      document what is known of their pathogenesis, clinical features, diagnosis and
      available treatment modalities. METHODS: Literature on the subject was reviewed
      using manual library search, articles in journals, internet search and conference
      abstracts. RESULT: Antiphospholipid antibodies have been detected in all age
      groups; incidence increases with age. They are antibodies to protein-phospholipid
      complexes and not to phospholipid alone. The most commonly detected
      antiphospholipid antibodies are lupusanticoagulant (LA), anticardiolipin
      antibodies and anti--2 glycoprotein-1 antibodies. Apart from thrombosis and
      recurrent foetal loss, they are also associated with neurologic disorders,
      cutaneous manifestations and thrombocytopaenia. CONCLUSION: Early detection
      requires a strong index of suspicion especially when thrombosis is seen at
      unusual sites. Several modalities of treatment such as anticoagulants and
      antiplatelet agents have been developed, though it is difficult to monitor level
      of anticoagulation as the antibodies may interfere with coagulation studies. Grey
      areas remain in the management of antiphospholipid antibodies; for instance it is
      not certain if patients with a positive laboratory test without any clinical
      feature should be treated.

PMID- 16649445
TI  - Concept and practice of evidence-based psychiatry and its application in Nigerian
      psychiatry: a critical review.
AB  - BACKGROUND: The practice of Evidence-Based Psychiatry started in the 1990's,
      however prior to this time the practice of psychiatry did have an evidenced base
      though not structured and systematically spelt out. This study aimed to review
      the development of the concept and practice of Evidence-Based Psychiatry and to
      identify position of Nigerian psychiatry in it. METHODS: Narrative reviews were
      made from information obtained from scientific publications i.e. (books and
      journals) and internet-based electronic articles. RESULTS: Evidence-Based
      Psychiatry emerged from Evidence-Based Medicine in the 1990's and aims to base
      practice on the best available evidence. The evidence is graded into A, B, and C,
      depending on the study design. Also critical to the practice of Evidence-Based
      Psychiatry is the availability of high-grade evidence and an efficient means of
      storing and retrieving it. Evidence-Based Psychiatry uses a systematic approach
      and involves five steps. Its scope covers aetiology, diagnosis, intervention, and
      prognosis. CONCLUSION: A comprehensive definition of Evidence-Based Psychiatry is
      given. There is a suggestion to change the term 'Evidence-Based' to 'Systematic
      Evidence-Based'. The right way to determine if a therapeutic intervention is
      evidence-based is to consider if the process that led to it is systematic in
      terms of the five steps of Evidence-Based Psychiatry. Nigeria is yet to develop
      structures required for Systematic Evidence-Based Psychiatry.

PMID- 16649446
TI  - Splenic changes in sickle cell anaemia.
AB  - BACKGROUND: The spleen is one of the most frequently affected organ in Sickle
      cell anaemia (SCA). This has been attributed to its complex anatomy and prominent
      reticuloendothelial functions which include clearance of unwanted particulate
      matter in blood ( culling), defense against infection and reservoir for blood
      cells. This paper aims to highlight the current information on the changes that
      occur in the spleen of Sickle Cell Disease patients in this environment. METHOD:
      A review of relevant literature on the subject of splenic changes in Sickle Cell
      Disease sourced by manual library and medline search. RESULTS: The essential
      splenic change in SCA is splenomegaly and subsequent shrinkage in size
      (autosplenectomy), which maybe due to several factors. These include: high levels
      of irreversible sickle cells, decreased HbF associated with increased
      intravascular sickling and chronic Malaria infection secondary to hyperplasia of
      the reticulo-endothelial system and increased antibody production especially IgG
      and IgM. Finally, the clinical complications of these splenic changes such as
      increased susceptibility to infection, acute splenic sequestration and
      hypersplenism are also reviewed in this paper. CONCLUSION: In view of the above
      changes, it is important to ensure regular monitoring and follow-up in order to
      prevent complications, recurrent crisis and death.

PMID- 16649447
TI  - Developments in caesarean section techniques: a review.
AB  - BACKGROUND: Caesarean section is the most common surgical procedure performed on
      women world-wide. It is recommended when vaginal delivery might pose a risk to
      the mother or baby. This review examines the history and developments in
      caesarean section techniques over the years as well as the difficulties that may
      be encountered in each stage in our environment. METHOD: A review of relevant
      literature was conducted using Pubmed and e-medicine websites for computer
      search. The following keywords were used: history, development, techniques and
      caesarean section. Relevant review articles, Cochrane database and chapters in
      text books were also used to extract information. RESULTS: Though practiced since
      ancient times, the history of caesarean section remains shrouded in myths as no
      document describing its indication and techniques is still available. Ancient
      medical writers like Galen, Hippocrates and Soranus made no mention of the
      procedure. However, the evidence that it was performed arose from legal texts.
      The development in its technique was gradual over many years. CONCLUSION: The
      development of caesarean section technique occurred with the withdrawal of
      surgeries from the stronghold of religion in Renaissance time. Operative
      techniques vary and this has continued to improve through many years of trial and
      error.

PMID- 16649448
TI  - Automated techniques in haematology.
AB  - BACKGROUND: Manual techniques have been mostly in use in developing countries
      until recently because of its low cost even though it is laborious. Many
      laboratories are however changing to automated techniques since many samples can
      be analysed within a short time. It is likely that more laboratories will use
      these instruments either as semi automated or fully automated multichannel
      instruments. There is therefore a need for laboratories to become more responsive
      to the needs of physicians making request by providing help in the presentation
      and interpretation of results. METHOD: Available literature on automation in
      Haematology was sourced for using both manual library search and Medline search.
      RESULTS: Quality control in automated blood cell counts and related topics are
      extensively researched but there is still dearth of knowledge on automation in
      other areas of Haematology and on the clinical implications of automation.
      CONCLUSION: It is therefore necessary to make provision for automated facilities
      in laboratories in view of the high precision and cost effectiveness of these
      machines. This review is geared towards a critical look at this technology and
      its application to disease states.

PMID- 16649449
TI  - Incisional hernia: a review.
AB  - BACKGROUND: Otherwise known as post operative ventral hernia, incisional hernia
      is a common complication following abdominal surgery and is a significant cause
      of morbidity. This review examines incisional hernia from its historical
      perspective to the present. METHOD: A Literature review of the topic was carried
      out using manual library search of journal articles on the topic published both
      locally and internationally. The search also made use of intemet material from
      Pubmed and Medline on relevant parts of the topic. All relevant articles from the
      reference lists of these papers were also studied. RESULT: Incisional hernia is a
      common complication of abdominal surgery. Its incidence is about 1% following
      primary healing and increasing to about 11% with postoperative wound infection.
      The most consistent causative factor is wound infection and the incidence may
      rise to 30% after abdominal wound dehiscenece and resuture. It may be difficult
      to repair and a wide range of surgical procedures have been developed for such
      repair. The repair may be direct suture or prosthetic mesh using the open or
      laparoscopic technique. Prosthetic mesh has revolutionized the repair of
      incisional hernias. Laparoscopic repair, which was introduced in the 1990's, has
      been adjudged feasible, safe and as effective as the open methods of repair.
      Recurrence rates of up to 49% with direct suture repair have been reported. Open
      and laparoscopic mesh repair have recurrent rates of 0-10% and 0-9% respectively.
      CONCLUSION: Despite improved surgical techniques and the use of prosthetic mesh
      incisional herniation remains a major problem for the general surgeon.

PMID- 16649450
TI  - Sero-prevalence of HIV antibodies in pregnant women in Port Harcourt, Nigeria.
AB  - BACKGROUND: The aim of the study was to determine the Sero-Prevalence of HIV
      antibodies in pregnant women attending the antenatal clinic at the University of
      Port Harcourt Teaching Hospital, Port Harcourt. METHOD: Serial recruitment of 600
      women who attended the antenatal clinic. HIV screening was done by rapid ELISA
      technique. Positive samples were re-tested with a second rapid ELISA kit, with
      only samples sero-positive with both kits being taken as trulysero-positive.
      RESULTS: The sero-positivity rate was 7.3%, sixty-nine point seven percent
      (69.7%) of all sero-positive cases were primiparae, with 84% in advanced stages
      of pregnancy (2nd and 31rd trimesters). History of blood transfusion, dental
      manipulations, tattooing and circumcision did not contribute significantly to
      increased HIV sero-positivity. CONCLUSION: There is high HIV sero-positivity rate
      among pregnant women attending antenatal clinic in Port Harcourt. The
      implications of this finding in relation to vertical transmission, transmission
      of nosocomial infection and increased occupational exposure of laboratory and
      hospital staff to HIV infection is discussed. Compulsory routine screening of all
      pregnant women attending antenatal clinics in Sub-Saharan Africa is advocated.

PMID- 16649451
TI  - Human immunodeficiency virus infection in a rural community of plateau state:
      effective control measures still a nightmare?
AB  - BACKGROUND: This study was designed to find out the prevalence of human
      immunodeficiency virus (HIV) infection in Zawan village as well as their socio
      cultural practices that promote its spread. METHODS: Three hundred subjects were
      recruited into the study comprising 193 males and 107 females by a simple random
      sampling method. A structured questionnaire was administered to each respondent
      and 5mls of blood collected and assayed for anit-HIV antibodies. The results were
      analysed using statistical software Epi-Info version 6, P < 0.05 was considered
      significant. RESULTS: The prevalence of HIV in Zawan village was found to be 8.3%
      (25 out of 300) and the significant risk factors noted were--use of sharp
      objects, trading and the divorce/separated group, (P < 0.05). Other factors such
      as tattooing, male circumcision by traditional method and tonsillectomy were not
      found to be statistically associated with HIV infection in this community, (P >
      0.05). CONCLUSION: HIV is still causing serious devastation in our rural
      communities. Hence government should supply affordable antiretroviral drugs to
      our rural dwellers, step up public enlightenment campaign and pursue with vigour
      the present micro-economic revival policies to alleviate abject poverty in our
      rural communities.

PMID- 16649452
TI  - Some haematological parameters in plasmodial parasitized HIV-infected Nigerians.
AB  - BACKGROUND: Nigeria is highly burdened by malaria and HIV-infection, yet
      researchers know little about the impact of this co-infection on the
      haematological profile of HIV-infected adult Nigerians. This case control study
      is an attempt to investigate the effect that HIV/malaria co-infection has on some
      haematological parameters of HIV-infected Nigerians. METHODS: Complete blood
      count (CBC) of 30 plasmodium parasitized HIV-infected subjects and 70 non
      parasitized controls were studied. RESULTS: Of the 30 parasitized subjects, 28
      (93.3%) were positive for falciparum malaria and 2 (6.7%) for vivax malaria. The
      incidence of anaemia, thrombocytopenia, neutropenia and leucopenia were
      significantly higher in parasitized subjects compared to non-parasitized controls
      66.7%, 60%, 36.7% and 63.3% versus 32.9%, 42.9%, 24.3% and 24.3% respectively. A
      statistically significant difference was observed between the haemoglobin,
      platelet count and the erythrocyte sedimentation rate (ESR) of parasitized and
      non- parasitized individuals (p < 0.05) respectively. A significant positive
      correlation was observed between the level of parasitaemia and anaemia (r = 0.37,
      p < 0.04) in parasitized subjects. The incidence of anaemia was two times higher
      in parasitized subjects compared to non-parasitized controls (66.7% versus
      32.9%). Red cell morphology showed a normocytic and normochromic picture in 40%
      and 67.1% of parasitized and non- parasitized individuals respectively.
      Microcytic, hypochromic picture was observed in 60% and 23% respectively in
      parasitized and non- parasitized individuals. Striking eosinophilia was seen in 5
      (16.7%) of parasitized and 3 (4.3%) of non-parasitized individuals. CONCLUSION:
      Incidence of cytopenia appear significantly higher in parasitized subjects
      compared to non-parasitized control and bring to bare the need for regular anti
      malaria prophylaxis for HIV-infected patients particularly in Nigeria.

PMID- 16649453
TI  - Absolute lymphocyte count as a marker for CD4 T-lymphocyte count: criterion for
      initiating antiretroviral therapy in HIV infected Nigerians.
AB  - BACKGROUND: Few laboratories in resource-constrained countries can afford to
      perform laboratory-monitoring tests required for the implementation of HIV
      therapy. In this case control study, we have investigated the relevance of
      absolute lymphocyte count as a surrogate marker for CD4 lymphocyte count as a
      criterion for initiating HAARTin HIV-infected Nigerians. METHODS: A total of 100
      consecutive recruited HIV-infected, previously antiretroviral naive persons and
      30 HIV-negative individuals blood samples were run for absolute lymphocyte and
      CD4 lymphocyte counts and results were compared by a model of linear regression
      analysis. RESULTS: An overall modest correlation was observed between absolute
      lymphocyte count and CD4 lymphocyte (r = 0.51) and at CD4 lymphocyte threshold
      relevant for clinical management of HIV-infected; <200, 200-350 and >350
      cells/microL (r = 0.41, 0.30 and 0.21) respectively. Mean absolute lymphocyte
      count of 1.60 +/- 0.77 x 10(9)/L, 1.88 +/- 1.11 x 10(9)/L and 2.04 +/- 0.54 x
      10(9)/L was equivalent respectively to CD4 of <200, 200-350 and >350
      cells/microL. CONCLUSIONS: This study indicates a modest correlation between
      absolute and CD4 lymphocyte counts of HIV-infected Nigerians and at CD4
      lymphocyte count threshold significant for clinical management of HIV-infected.
      Absolute lymphocyte count can become a minimal inexpensive alternative to CD4
      lymphocyte count in conjunction with WHO staging and clinical status of patient
      in determining the optimal time to initiate therapy particularly in resource
      limited settings where other expensive methods of CD4 enumeration are
      unavailable.

PMID- 16649454
TI  - Comparative study of haematological values using manual and automated techniques
      in apparently healthy adult Nigerians.
AB  - BACKGROUND: Many public medical laboratories use automated techniques for
      analysis of samples due to the few number of laboratory staff required and the
      speed at which it operates. This study was carried out to compare haematological
      values obtained from automated techniques and manual techniques. METHOD: A total
      of 86 apparently healthy adult Nigerians, aged 18-50 years comprising 50 males
      and 36 females who came for medical examination between June, 2004 and May, 2005
      at Aminu Kano Teaching Hospital, Kano were used for the study. Standard manual
      methods and cell-dyn 3700cs system techniques were used to determine haematocrit,
      total and differential leucocyte counts. RESULTS: Statistically significant
      differences were found between automated and manual techniques in males with
      regard to haematocrit levels, total white cell counts, differential monocyte and
      basophil counts (0.45 +/- 0.031/1, 5.1 +/- 1.9 x 10(9)/l, 0.54 +/- 0.19 x 10(9)/l
      and 0.11 +/- 0.08 x 10(9)/l respectively) for automation and 0.42 +/- 0.041/l,
      4.4 +/- 1.4 x 10(9)/1, 0.05 +/- 0.06 x 10(9)/l and 0.004 +/- 0.013 x 10(9)/l
      respectively for manual methods at P < 0.001, P < 0.05, P < 0.001 and P < 0.001
      respectively while there were no significant differences in differential
      neutrophil, lymphocyte and eosinophil counts (2.1 +/- 0.7 x 10(9)/l, 2.2 +/- 0.7
      x 10(9)/l and 0.14 +/- 0.16 x 10(9)/l respectively) of the automation when
      compared to 2.1 +/- 0.5 x 10(9)/l, 2.1 +/- 0.5 x 10(9)/l and 0.09 +/- 0.09 x
      10(9)/l respectively using manual methods (P > 0.05). There were no statistically
      significant differences between automated and manual methods in females with
      regard to total white cell count, differential neutrophil, lymphocyte and
      eosinophil counts (5.8 +/- 2.3 x 10(9)/l, 2.6 +/- 0.9 x 10(9)/l, 2.4 +/- 0.8 x
      10(9)/l and 0.1 +/- 0.1 x 10(9)/l respectively) of the automation when compared
      to 4.9 +/- 1.6 x 10(9)/l, 2.5 +/- 0.7 x 10(9)/l, 2.3 +/- 0.6 x 10(9)/l and 0.06
      +/- 0.09 x 10(9)/l respectively of manual techniques (P > 0.05) while significant
      differences were observed in haematocrit, differential monocyte and basophil
      counts (0.39 +/- 0.03 l/l, 0.55 +/- 0.3 x 10(9)/l and 0.1 +/- 0.09 x 10(9)/l
      respectively) of automation when compared to 0.37 +/- 0.03 l/l, 0.03 +/- 0.04 x
      10(9)/l and 0.002 +/- 0.01 x 10(9)/l respectively of the manual methods at P <
      0.01, P < 0.001 and P < 0.001 respectively. CONCLUSION: The results have proven
      that differential monocyte and basophil counts from automation are unreliable and
      efforts should be made to carry out manual differential counts for confirmation.

PMID- 16649455
TI  - Default from tuberculosis treatment programme in Sagamu, Nigeria.
AB  - BACKGROUND: The study was embarked on to determine the risk factors associated
      with default from tuberculosis treatment in Sagamu, Nigeria. METHODS: A
      retrospective study of 774 adult patients aged 15 years and above registered for
      antituberculosis DOTS therapy was conducted between January 1997 and December
      2003 at the Department of Community Medicine and Primary Care, Olabisi Onabanjo
      University Teaching Hospital, Sagamu, Nigeria. Patients who defaulted (cases)
      during the course of treatment were compared with non-defaulters (controls) who
      commenced and completed their TB treatment at the same time. RESULTS: There were
      178 (23%) defaulted cases during the study period. Defaulting rate was highest
      (78.1%) during the continuation phase of the treatment. There was a significant
      downward trend in default rate from 37.9% in 1997 to 8.4% in 2003 (p < 0.001).
      HIV-positive patients had twice the risk of default during the intensive phase of
      treatment than HIV-negative patients (OR 2.61: CI 0.84-7.97; P = 0.06). Important
      risk factor associated with non-compliance was male sex 9 OR 1.64: CI. 1.15-2.34;
      p < 0.01). HIV status (OR: 1.4 CI: 0.77-2.57; p > 0.05), previous treatment (OR:
      0.75 CI: 0.43-1.30: p > 0.05), sputum smear result (1.02: CI: 0.59-1.74: p >
      0.05) were not significantly associated with default from treatment. CONCLUSION:
      Defaulting was higher in men than women. A downward trend over time was observed.
      Alternative strategies such as the use of family members to oversee treatment may
      be desirable in men. There is also a need to shorten duration of treatment,
      decentralize and make DOTS more accessible, and ensure adequate uninterrupted
      drug supply to TB treatment centres.

PMID- 16649456
TI  - Radiograghic evaluation of lymphadenopathy in pulmonary tuberculosis in
      Northeastern, Nigeria.
AB  - BACKGROUND: There is changing pattern of presentation of tuberculosis in the era
      of HIV Lymphadenopathy is one of the most important manifestations of
      tuberculosis, hence the need for the evaluation of its radiologic patterns.
      METHODS: A multi-centre retrospective study of chest radiographs of 116 adult
      patients diagnosed bacteriologically (positive sputum smear) as pulmonary
      tuberculosis was conducted in the University of Maiduguri Teaching Hospital,
      Maiduguri, and Federal Medical Centre Nguru, in Bomo and Yobe States, Nigeria,
      respectively between April 2003 and March 2004. Lymphadenopathy was assessed in
      all the radiographs. RESULTS: Of the one hundred and sixteen radiographs of
      patients analyzed, there were 83 (71.6%) males and 33 (28.4%) females with mean
      age of 37.99 +/- 14.11 years. A total of thirty eight patients (32.7%) presented
      with lymphadenopathy with the highest frequency in the left hilar region (12.9%).
      Bilateral hilar and paratracheal lymphadenopathy were the lowest with equal
      percentages (4.3%). Left, right and bilateral hilar enlargement were more common
      in males than females (p < 0.000) and more patients had left hilar (15) than
      right hilar (13) enlargement (p = 0.030). Only 3 (2.6%) out of all the patients
      presented with lymph node calcification. CONCLUSION: In conclusion, there is a
      rise in the prevalence of lymphadenopathy among pulmonary tuberculosis patients
      when compared to a previous study done in the pre-HIV era in Nigeria.

PMID- 16649457
TI  - Trauma related to sexual assault in Calabar, south eastern Nigeria.
AB  - BACKGROUND: A woman who is sexually assaulted experiences intense anxiety and
      fear. The associated stigmatization often results in under reporting and
      management difficulties. The aims of this study are to document the types of
      injuries seen in victims of sexual assault and to highlight problems in
      management of cases. METHOD: Twenty-two case files of sexual assault victims
      between January 1998 and December 2001 were reviewed for age, types of injuries
      sustained and treatment received. RESULT: Age range of all victims was 4 to 23
      years. The knife was used by the perpetrator in 8 (36.4%) cases. Time interval
      between assault and presentation to hospital was up to 12 hours in 13 (59.1%)
      cases. Superficial abrasions, bruises, and lacerations were observed in 12
      (54.6%) cases. Six (27.3%) victims paid for human immunodeficiency virus screen
      and the results were non-reactive. Ten (45.5%) victims had primary repair of
      perineal tear. CONCLUSION: Sexual assault is associated with multiple bruises,
      lacerations, and perineal tears. Commercialization of medical services was a
      hindrance to proper management of cases.

PMID- 16649458
TI  - Obstetric mortality in a Nigerian general hospital.
AB  - BACKGROUND: The aim of the study was to evaluate the progress towards achieving a
      50% reduction in maternal mortality by the year 2000 at a referral hospital.
      METHODS: A retrospective review of births and maternal deaths over an 18-year
      period from 1981 to 1998. RESULTS: There was a 30% reduction among booked women
      in the period 1990-1998 compared to 1981-1989 while only 8% reduction was
      achieved among referred women. Infection and hypertensive disorders remained the
      leading causes of death but the contribution of haemorrhage declined due to
      improved blood transfusion services. CONCLUSION: Further improvement in maternal
      survival can be achieved by training health personnel involved in maternity care
      to recognise or anticipate complications early and refer.

PMID- 16649459
TI  - Postpartum perineal pain in primiparous women: a comparison of two local
      anaesthetic agents.
AB  - BACKGROUND: Episiotomy is the commonest obstetric surgical operation performed to
      increase the introitus to enhance vaginal delivery. This study was to compare the
      effect of two local anaesthetic agents on postpartum perineal pain and time for
      demand for oral analgesics. METHODS: A randomized double-blinded controlled
      clinical trial was conducted in primiparous women who had spontaneous vaginal
      delivery, comparing 1% plain lidocaine and 0.25% plain bupivacaine infiltration
      for the repair of selective episiotomy or perineal injury. RESULTS: The two
      groups were comparable in sociodemographic characteristics. At 2 and 4 hours,
      women who had perineorraphy under lidocaine had significantly higher pain scores
      on the Visual Analogue Scale (VAS) than those who had the repair under
      bupivacaine, (4.0 v. 2.0)and(6.0 v. 3.0)respectively. At the 6h hour, the mean
      pain score for the bupivacaine group was 4.0 on the VAS while the lidocaine group
      had already received a dose of oral analgesic (Ibuprofen 400 mg) following severe
      pain from the repair. There was however no statistically significant difference
      in the pain score on the VAS between the two groups at the time of request for
      oral analgesics. The mean time lapse before demand for oral analgesics for the
      lidocaine group was 2.25 +/- 0.46 hrs (Mean+Standard deviation) while that for
      the bupivacaine group was 7.13 1.56 hrs (Mean Standard deviation). The P value
      was P < 0.0000 (Student's t-test) and statistically significant. CONCLUSION: It
      is concluded that the patients in the bupivacaine group had a prolonged analgesia
      and needed fewer doses of oral analgesics in the immediate postpartum perineal
      repair period.

PMID- 16649460
TI  - Fractures in children.
AB  - BACKGROUND: The burden of diseases in children in our environment is dominated by
      infections and malnutrition; paediatric trauma has low advocacy and as such is
      given scant attention. The aim of this study is to review and describe the
      pattern of paediatric fractures in our local setting. METHOD: A retrospective
      review of all the medical records of children below the age of fourteen years who
      were admitted to our center on account of major trauma between January 1999 and
      December 2003 was done. Those with incomplete records were excluded. RESULTS: The
      patients ranged in age from 1 +/-13 years with mean of 6.7 +/- 2.9 years. They
      were mostly males 60 (61.2%) and females 38 (38.8%). The causes of the accidents
      were diverse. Road traffic accidents were most common 47(51%). A great number of
      these resulted from unguarded children hit by motor vehicles while crossing the
      road 33 (36.7%). Forty-one (41.8%) patients fell from various heights. Of these
      number thirty (30.6%) fell while playing. Most fractures were close 70 (71.4%)
      while 25 (25.5%) were open fractures and 3 (3.1%) pathological fractures. The
      most common site of injury was the femoral shaft 33.7%; this was followed by
      fractures of the supracondylar region of the humerus 17.3%, distal radius 15.3%
      and tibialfibula 15.3%. More than half of the patients 58 (59.2%) presented fresh
      to our hospital, while 27 (27.6%) presented initially to traditional bonesetter
      (TBS) and 13 (13.3%) were referred from private practitioners. Of those twenty
      seven patients from the TBS, seven came with compartment syndrome and three had
      frank gangrene. Most of the patients were managed conservatively. Preliminary
      traction followed by plaster of Paris (POP) application in 36 (36.7%), and
      manipulation under anaesthesia (M.U.A) and POP (30.6%), were common definitive
      treatments given. Sixteen patients (16.3%) had open reduction and internal
      fixation. Acute compartment syndrome 7 (7.1%) and frank gangrene 3 (3.1%) were
      the commonest complications and were due to late referral by traditional
      bonesetters. CONCLUSION: In our environment, fractures in children are common and
      are frequently associated with morbidities due to interference by traditional
      bonesetters. These injuries are highly preventable and paediatric trauma
      prevention strategies directed at parents, children as well as other road users
      would help to reduce the burden of such fractures especially in the developing
      countries where the burden of other childhood diseases obscures trauma care.

PMID- 16649461
TI  - A simple lithotomy device for children.
AB  - BACKGROUND: The position of the patient is important for good access during
      surgery. The aim of this paper is to present a simple lithotomy device for
      children. METHOD: We present a simple easy-to-construct and affordable lithotomy
      device utilizing locally available materials for paediatricpatients. RESULTS: A
      simple, cheap and easy-to-construct lithotomy device for children has been used
      in our centre. It is also easy to sterilize and very durable. No complication has
      been noticed so far that is attributable to the lithotomy device. It has been
      used for Swenson's procedure for Hirschsprung's disease, and rectal biopsy.
      CONCLUSION: The affordability of the device will save hospital administrators and
      the country great cost while still being effective. The device is being
      recommended for use in developing countries where paediatric operating tables are
      not available.

PMID- 16649462
TI  - Gossypiboma: a report of 2 cases.
AB  - BACKGROUND: Retention of surgical sponges in body cavities (gossypiboma) is
      preventable. It is probably under reported, may be for medicolegal reasons. We
      report 2 cases we have managed, one at a tertiary medical centre, and the other,
      at a private clinic in Port Harcourt, in order to re-awaken the awareness of its
      occurrence and make a plea for caution during surgery. METHODS: The case notes of
      patients treated surgically over the period between 1995 and 2004 were reviewed
      for cases of retained surgical sponges. RESULTS: Two cases were identified over
      the period 1995 to 2004. One had presented acutely while the second case
      presented in a sub-acute manner. Both required re-exploration and retained
      sponges were retrieved. CONCLUSION: It may not be possible to eradicate the
      occurrence of retained sponges in the body but it can definitely be minimized,
      thus saving many patients from the associated agony.

PMID- 16649463
TI  - Mechanical airway obstruction from the laryngeal mask airway cuff.
AB  - BACKGROUND: The laryngeal mask airway (LMA) classic has been found useful in
      airway management of both routine and emergency unexpected failed intubations. We
      report a case of mechanical airway obstruction from anterior in folding of the
      laryngeal mask airway classical cuff. METHOD: The anaesthetic record of a 55-year
      old 70 kg female patient fora left sided total hip replacement that had a failed
      spinal and was augmented with the laryngeal mask airway. RESULT: Near complete
      airway obstruction developed after the size 4 laryngeal mask airway classic was
      inserted and the cuff inflated with 30 ml of air. The reduced reservoir volume
      and the desaturation that ensued as detected by the portable handheld pulse
      oximeter alerted the anesthesiologist and called for a check which was not
      corrected by any head and neck manoeuvre. On withdrawal of the laryngeal mask
      airway, the cuff was noted to have folded unto the fresh gas aperture thereby
      obstructing ventilation and oxygenation of the patient. CONCLUSION: Monitoring
      the monitors and quick reassessment of laryngeal cuff placement guaranties the
      evasion of anaesethetic catastrophes.

PMID- 16649464
TI  - Clinical photographic quiz. Laryngocoele.

PMID- 16649465
TI  - Clinical photographic quiz. Ameloblastoma.

PMID- 16649466
TI  - Clinical photographic quiz. Nasal polyposis, inverted papilloma, sino-nasal
      tumour, rhinoscleroma.

PMID- 16649467
TI  - "The medical doctors": an endangered professional group: can democracy save them?

PMID- 16649468
TI  - Understanding the terrorism threats posed to medical technology.

PMID- 16649469
TI  - Handling equipment installation and training challenges.

PMID- 16649470
TI  - Finding a home for unwanted equipment.

PMID- 16649471
TI  - Understanding the safety features of electrosurgical units.

PMID- 16649472
TI  - Tackling challenges to the PM process.

PMID- 16649473
TI  - Guidelines for design: Mapping out the ideal clinical engineering department.

PMID- 16649474
TI  - Continuing education offers benefits for biomeds, employers.

PMID- 16649475
TI  - Reach out and make a connection.

PMID- 16649476
TI  - Manage contractors like employees to ensure JCAHO compliance.

PMID- 16649477
TI  - Pumping up your insufflator troubleshooting skills.

PMID- 16649478
TI  - Competency testing demonstrates, strengthens staff abilities.

PMID- 16649479
TI  - Is singularity on the horizon?

PMID- 16649480
TI  - Portable X-ray machines.

PMID- 16649481
TI  - Increase patient safety by creating a quieter hospital environment.

PMID- 16649482
TI  - Effective training yields learning and growth.

PMID- 16649483
TI  - A prototype infant incubator for heliox therapy.
AB  - Heliox (Hx) gas has been shown to improve pulmonary function in infants, but
      methods for its delivery are invasive and problematic. To this end, we modified
      an Isolette (Hill-Rom Air-Shields) infant incubator (Hxl) to deliver Hx
      respiratory gas mixtures noninvasively while providing thermal stability for
      neonatal care in the Neonatal Intensive Care Unit (NICU). In vitro tests and in
      vivo animal studies were performed to compare the original design specifications
      and established baseline performance criteria for the Hxl design. The
      experimental environments at 50% and 80% relative humidity (RH) consisted of
      helium (He) with 21% and 50% O2 and control (C) of 21% and 50% O2 with the
      balance nitrogen (N). Elapsed times to steady state (SS) and recovery time back
      to SS (OCDss) due to opening and closing the door were recorded for each
      variable. All rabbits survived and appeared comfortable during all experimental
      conditions. These data show that the newly designed Isolette provides similar
      thermal, O2, CO2, and RH responses as the control incubator. Based on these
      positive safety/efficacy studies, study of the therapeutic impact of Hxl care on
      neonatal growth and development is in progress.

PMID- 16649484
TI  - Recognizing the need for harmonized standards.

PMID- 16649485
TI  - Preventive maintenance: a look at the big picture.

PMID- 16649486
TI  - Unseen observer: putting practice into practice.

PMID- 16649487
TI  - What is the right answer?

PMID- 16649488
TI  - Keep the kids together.

PMID- 16649489
TI  - The sci-fi life.

PMID- 16649490
TI  - Electronically speaking.

PMID- 16649491
TI  - Dangers of a wireless world.

PMID- 16649492
TI  - Are you a fraud?

PMID- 16649493
TI  - Billing for better results. Interview by Kathyrn Robyn.

PMID- 16649494
TI  - "The pen is mightier...".

PMID- 16649495
TI  - Beyond the basics: prehospital assessment and care of the stroke patient.

PMID- 16649496
TI  - Breaking down barriers.

PMID- 16649497
TI  - How Iowa got the mumps.

PMID- 16649498
TI  - Water treatment in domiciliary hemodialysis equipment: ultraviolet irradiation
      and Sartobind membrane.
AB  - Water is a fundamental element in any hemodialysis device. It must be safe, free
      not only of micro-organisms but also of any organic or inorganic chemical
      contaminant. Up to now ion exchanger, reverse osmosis, activate carbon and
      chlorine are generally used for this purpose. The results are not satisfactory.
      Microbial contaminants survive and at some points multiply. Pyrogens and
      endotoxins are not completely eliminated. Chlorine itself adds more risk factors
      because of the compounds deriving from its interaction with organic molecules. A
      system to obtain safe water in hemodialysis equipment is described. It is based
      on the use of ultraviolet irradiation to eliminate any microbial contaminant and
      on Sartobind membranes to eliminate pyrogens, endotoxins, proteins and other
      unwanted molecules. Mobile domiciliary hemodialysis equipment was used.
      Ultraviolet lamps (30 mW/cm2) were applied at two points: after the ion exchange
      and after the reverse osmosis. Three Q100 Sartobind membranes were positioned
      immediately before the monitor. The values of cfu/mL counted in the water after
      the ion exchange ranged from 450 to 1,990, whereas before the monitor they
      dropped from 0.01 to 0.09 cfu/mL. The LAL test, positive before the Sartobind
      membrane, was negative thereafter. The system proposed has shown to be effective
      in guaranteeing safe water free of micro-organisms and endotoxins.

PMID- 16649499
TI  - [Microbiological verification of a self control plan for a hospital food
      service].
AB  - During the past years, it has been an increment of food related infectious
      diseases. In order to avoid micro biological food contamination, adherence to
      good manufacturing is required through control measures of food safety practices.
      Updated national and European regulations underline the need to apply the HACCP
      system, overcoming the old concept of sample control on the end user product.
      This work shows results of microbiological controls made along the whole
      productive chain. Measurements are made using biomolecular techniques (PFGE) in
      order to assess the management of the micro biological risk of the self control
      plan applied to a hospital food service of Naples. The use of the PFGE applied on
      some micro-organisms gram negative potentially pathogen, underlines the
      circulation, continued in time, of these micro-organisms within the cooking area.
      In addition, cross contamination between several matrixes of samples has been
      detected.

PMID- 16649500
TI  - [Prevalence of risk factors for ischemic heart disease in a northern Italian
      adult population].
AB  - The aim of this study is to measure the prevalence of cardiovascular risk factors
      in Tavazzano (Lodi) inhabitants, in order to implement efficacious and preventive
      strategies at community level. In 1998 the target population consisted of 2055
      adults (males and females) aged 35-64, living in Tavazzano (Lodi province). The
      examined population was made of 856 subjects (399 males and 457 females), with a
      participation rate equal to 41,6%. A questionnaire concerning medical history and
      life habits such as: smoking, alcohol consumption and physical activity was
      administered to each participant. Height, Weight, Systolic and Diastolic Blood
      Pressure, Fasting Blood Glucose, Total Cholesterol and triglycerides were
      collected. A 12-leads electrocardiogram, evaluated both with standard clinical
      criteria and Minnesota Code, was done for each subject. The results show a high
      prevalence of modifiable cardiovascular risk factors: hypertension (25,2%),
      smoking (26,1%), obesity (14,6%), hypercholesterolemia (27,5%), low physical
      activity (39,6%) mainly in males and with an increasing trend with age. These
      data indicate the need of preventive programmes addressed to the general
      population and to "subjects at risk", according to the National Health Plan 2003
      2005.

PMID- 16649501
TI  - [The HACCP method for personnel education].
AB  - In order to guarantee an alimentary safety it is necessary to estimate the real
      meant sanitary risk as probability of insurgence of microbiological pathologies
      and to develop the concepts of the HACCP therefore as indicated from D.lgs.
      155/97. In six scholastic catering services, some which three had applied system
      HACCP and three not, have been conduct microbiological analyses on the
      superficial ones, the staff and the alimony. It has been estimated the
      effectiveness of the system HACCP observing the modifications been necessary
      during the trend temporal, through 5 series of samples, carried out in three
      years 2000-2002. The not optimal situation emerged from the search confirms that
      the use of the handbook of CPI and the self-control based on method HACCP needs
      of time and professional contributions for one they corrected management.

PMID- 16649502
TI  - [Efficient prevention of overweight and obesity in the experience of family
      practitioners and "nutrition units" of the public health system in Lombardy].
AB  - General practitioners (GP's) presence is homogeneously distributed in the
      Lombardy territory. GP's are easy accessible by people so they could play a key
      role in the prevention of overweight and obesity. In this study GP's included in
      everyday medical activity a primary prevention strategy regarding nutrition and
      lifestyle. The goal was to maintain a constant BMI for one and a half year for at
      least 50% of the patients (stable means without progression within BMI's range).
      During the same time another endpoint was to decrease from 1 to 3 units the BMI
      in overweight patients in half of the observed population. Subjects were randomly
      recruited during routinely ambulatory activity, without a specific BMI based
      selection. Diet quality was assessed with a food frequency questionnaire
      regarding "protective foods" as vegetables, fruits and legumes. Some "basic"
      information about nutrition and lifestyle where then provided through explanation
      of issues printed on A4 page brochure. Percentage BMI's range variation before
      and after the intervention show a stability in the observed population, with an
      increase 0,3% for normal weight males and 0,9% for females. BMI was constant in
      72,2% of the subjects considering a 1 unit variation and in 92,2% considering 3
      units variation. Within subjects who varied 1 unit (27,7%) more subjects
      decreased rather than gained weight (16% vs 11,7%); within subjects who varied 3
      units (7.8%), 4,5% decreased and 3,3 increased their BMI. GP's demonstrate to
      have an efficient role in weight gain control with a simple and regular
      prevention strategy towards healthy lifestyles and simple nutritional tips. It is
      important for patients to comprehend the importance the doctor give to the
      overweight and obesity problem, apart from the medical issue considered during
      the visit. GP's have a key role for healthy life-style change programs among
      their patients. These results provide new arguments about the opportunity to
      invest public resources towards population (managed in collaboration with GP's
      coordinated by a public health department such as NU), rather than towards a
      single patient. The project management was supervised by the Nutrition Unit (NU)
      of the public heath system SIAN (ASL di Brescia).

PMID- 16649503
TI  - [Evaluation of the appropriateness of hospital admissions using the iso-gravity
      classification systems APR-DRG and Disease Staging and the Italian version of
      Appropriateness Evaluation Protocol (AEP)].
AB  - Our main purpose was to evaluate the organizational appropriateness of admissions
      made in a university hospital, by comparing two iso-gravity classification
      systems, APR-DRG and Disease Staging, with the Italian version of AEP (PRUO). Our
      analysis focused on admissions made in 2001, related to specific Diagnosis
      Related Groups (DRGs), which, according an Italian Law, would be considered at
      high risk of inappropriateness, if treated as ordinary admissions. The results
      obtained by using the 2 classification systems did not show statistically
      significant differences with respect to the total number of admissions. On the
      other hand, some DRGs showed statistically significant differences due to
      different algorithms of attribution of the severity levels used by the two
      systems. For almost all of the DRGs studied, the AEP-based analysis of a sample
      of medical records showed an higher number of inappropriate admissions in
      comparison with the number expected by iso-gravity classification methods. The
      difference is possibly due to the percentage limits of tolerability fixed by the
      Law for each DRG. Therefore, the authors suggest an integrated use of the two
      methods to evaluate organizational appropriateness of hospital admissions.

PMID- 16649504
TI  - [Evaluation of the appropriateness of hospital admissions with the Italian
      version of the AEP in a university hospital].
AB  - It has been carried out a survey to evaluate the appropriateness of hospital stay
      in a university hospital. The aims of the study were: to determine the amount of
      inappropriate hospital admissions and inappropriate days of stay in relation to
      either wards and characteristics of admission; to analyse the reasons for
      inappropriate patient stay. A randomised sample stratified by ward of discharge
      of 224 medical records were analysed using the Italian version of the
      Appropriateness Evaluation Protocol. 37.9% of the hospital admissions and 18.9%
      of hospitalisation days were judged to be inappropriate. The main reasons for
      categorising an admission or a day of stay as inappropriate were a) delay in
      performing elective surgery procedures; b) that the patient's problem could be
      treated on an outpatient basis; c) delay in performing diagnostic examinations.
      The univariate statistical analysis showed an association between appropriateness
      of hospital stay and gender age, ward of discharge, length of hospital stay and
      DRG type (medical/surgical). The study highlights a lower level of
      inappropriateness compared to the results of other investigations. Hints were
      also identified for achieving an improved efficiency at hospital level.

PMID- 16649505
TI  - [Evaluation of ambulatory medical care in Milan].
AB  - Ambulatory procedures are an essential component of health care both for their
      number and for their cost. We aim therefore to identify and to quantify the
      volume of ambulatory procedures performed in Milan during 2003. The data come
      from the Outpatient Care Information Report that collect much information by
      characteristics of patient, health care institution and procedure categories. The
      analyses in this report are based on absolute measures, utilization rates and
      concentration index. During the year 2003 nearly 20 millions of ambulatory
      procedures were performed in the public and private outpatient facilities of
      Milan for the resident population. The average annual rate was 15 procedures per
      person. Utilization varied according to patient age and sex, higher in women and
      in the elderly group, statistically significant variability is observed
      (p<0.001). Outpatient care accounts for high density supply (124 specialty points
      for 100,000 inhabitants). Utilization rate was not homogenous both for the
      medical specialties and for the geographical district distribution, all that, it
      seems depending on the activity concentration differences and complexity supply
      of services than on a different distribution of health needs. This analysis may
      be useful as methodological starting point for further investigating current
      outpatient care data and for identifying those sectors in need of corrective
      actions.

PMID- 16649506
TI  - [Hospital at home: assessment of early discharge in terms of patients mortality
      and satisfaction].
AB  - New organizational models are essentials for European Hospitals because of
      restraining budget and ageing of population. Hospital at home is an alternative
      to inpatient care, effective both in clinical and economic ground. The aim of our
      study was to evaluate the impact of Hospital at Home in terms of decreased
      mortality and patient satisfaction. We carried out a meta-analysis of the
      literature about hospital at home interventions. We searched Medline (to December
      2002), the Cochrane Controlled Trials Register (to October 2002) and other
      bibliographical databases, with a supplementary handsearching of literature. We
      used the following keywords: hospital at home, home hospitalization, mortality,
      patient satisfaction, cost, acute hospital care, conventional hospitalization. We
      included studies respecting the following criteria: analytical or experimental
      studies aimed at compare early discharge to hospital at home and continued care
      in an acute hospital. Review Manager 4.2 software was used to collect data and
      perform statistical analysis. We found 2420 articles searching for the chosen
      keywords. Twelve studies (2048 patients) were included for death outcome and six
      studies (1382 patients) were included for satisfaction outcome. The selected
      studies indicated a greater effect size of patient satisfaction in home patients
      than hospitalized ones (Odds Ratio: 1.58 95% CI: 1.25, 2.00) and showed no
      difference in terms of mortality (Risk Difference: -0.01 95% CI: -0.03, 0.02).
      Our results underline the effectiveness of this organizational model, as an
      alternative to continued care in an acute hospital. Further useful considerations
      could be drawn by economic evaluation studies carried out on field.

PMID- 16649507
TI  - [Development of a technique for recovering Giardia cysts and Cryptosporidium
      oocysts from fresh vegetables].
AB  - Techniques described for recovering Giardia and Cryptosporidium (oo)cysts from
      fruit and vegetables are generally inadequate and present variable recovery
      efficience and elevated costs. The aim of our study was to evaluate the recovery
      efficiency of a simple and economic technique to apply either to berry
      vegetables, like tomatoes and peppers, or to large leave vegetables, like lettuce
      and chicory. The method include contamination and further elution of the
      vegetables. Then sedimentation of (oo)cysts by centrifugation of the eluate of
      vegetables and their visualization by means of direct immunofluorescence. The
      higher recovery values for both protozoa were obtained in large leave vegetables
      with mean data above 70% for Giardia and 76% for Cryptosporidium, whereas the
      values observed in the berry vegetables were above 43% for Giardia and above 37%
      for Cryptosporidium on average.

PMID- 16649508
TI  - [Compliance with handwashing in health care settings].
AB  - Many studies report low compliance with handwashing in health care settings, even
      if it is considered an important factor to reduce cross transmission. METHODS:
      Observational study in University Hospital with external observers. RESULTS: The
      observers recorded 1262 opportunities for handwashing among 49 nurses. The
      average of the opportunities was 8,8 handwashing/hour (d.s. +/- 5.05, range 0
      divided by 23). The compliance was 19,3%. Compliance was higher in intensive care
      unit (25,6 %) than in medical ward (18,1 %) and surgical ward (13,9 %). There
      were no difference between males (19 %) and females (19.4%). Compliance with
      handwashing was significantly better in post procedure (34%) than in pre
      procedure (10.6%) and was worst when the workload was higher. CONCLUSIONS: The
      study confirms the low adhesion to handwashing international recommendations and
      suggests to adopt "ad hoc" educational programs and suitable structural/operative
      conditions.

PMID- 16649509
TI  - [Removal of Cryptosporidium and Giardia in drinking water treatment in a Tuscan
      area].
AB  - Five drinking water treatment plants in the Tuscan area, differing in relation to
      the treatments employed, were monitored for the presence of Cryptosporidium and
      Giardia (oo)cysts in order to estimate their removal capacity of each works.
      Twenty-eight water samples (16 from inflow raw water and 12 from outflow drinking
      water) were analysed during the one-year survey. The US EPA 1623 method was used,
      obtaining, according to the PHLS quality control system, a recovery rate of 51.3
      +/- 22.9% for Cryptosporidium oocysts and 48.8 +/- 20.7% for Giardia cysts. The
      results showed that both the protozoa were present in surface raw waters:
      Cryptosporidium in 62.5% and Giardia in 87.5% of the samples. Considering the
      outflow drinking waters, the removal capacity varied from 100% in the
      technologically more complex plant (which supplies most of the area), to at least
      90% in the remaining four plants, where less complex treatments are carried out.
      The occurrence of (oo)cysts was not associated with seasonality, turbidity or
      Clostridium perfringens (Cl. perfringens seems to be related with Cryptosporidium
      oocysts in surface raw waters; in this respect, our legislation states that the
      protozoa have to be searched for whenever a water sample is positive for Cl.
      perfringens). We confirmed the validity of the US-EPA 1623 method in assessing
      and managing the risk associated with waterborne protozoa, thus a valid tool to
      safeguard the population from exposure to such pathogens.

PMID- 16649510
TI  - [Sensitivity and accuracy of health databases in determining incidence of
      lymphoid malignancies in an Italian population].
AB  - We examined the sensitivity and the accuracy of three health databases (hospital
      discharge data, death certificates and pathologic records) between 1997 and 2001
      in an Italian community, to evaluate their accuracy for the diagnosis of lymphoid
      malignancies and their ability to detect newly diagnosed patients affected by
      these diseases. Hospital discharge data showed the best sensitivity among the
      examined databases, though they exhibited an unexpectedly high number of
      diagnostic errors, even when limiting the analysis to patients with repeated
      hospital admissions over time. Overall, the pathologic registry and the death
      certificate file showed a higher diagnostic accuracy, though their sensitivity
      was considerably lower than hospital discharge data.

PMID- 16649511
TI  - ["Initiative" in primary care: survey on hypertension prevalence and definition
      of cardiovascular risk profile in ASL 3 of Lagonegro (PZ)].
AB  - The objective of our study was to estimate the prevalence of not-diagnosed
      hypertension and to determine 10-year risk of coronary heart disease in a random
      sample of individuals in ASL 3 of Lagonegro (PZ). The sample was based on the
      whole population assisted by 21 General Practitioners. All General Practitioners
      filled a form for each patient containing social-demographic, anthropometric and
      clinical data. The study included only patients aged 35 to 74 years, without a
      previous diagnosis of myocardial infarction, congestive heart failure and that
      were not taking antihypertensive drugs (N=335). The directly standardized
      prevalence of prehypertension was 0.54 (IC95%: 0.47-0.59) and that of
      hypertension was 0.33 (IC95%: 0.28-0.38). The prevalence of both, prehypertension
      and hypertension was higher in males than in females, as well as in old compared
      to young adults. Cardiovascular risk factors as Body Mass Index (BMI), diabetes,
      a family history of dyslipidemia and diabetes were more frequent among
      prehypertensive and hypertensive individuals, than in normotensive ones. We also
      estimated the risk of an acute coronary event in patients whit blood pressure
      higher than 140/90 mmHg. The calculation, carried out through Framingham
      algorithm, showed that 1 out of 10 hypertensive subject had a 10-years risk of
      developing coronary heart disease and that males had a higher risk compared to
      females. Our study highlights the fundamental role of General Practitioners may
      play in earlier diagnosis prehypertension and hypertension in the general
      population, thus adopting practices oriented to healthy promotion and prevention.

PMID- 16649512
TI  - Relationship between pathological gambling, alcoholism and drug addiction.
AB  - The aim of this survey was to evaluate the distribution of pathological gamblers
      treated in an alcohol or drug addiction treatment program run by the Italian
      National Health Service providing assistance to alcohol and drug abusers in
      Venice (North east Italy) from September 1 to December 31, 2001. Each drug- or
      alcohol-dependent patient retained for treatment for at least one month was
      administrated an anonymous precoded questionnaire to collect personal and socio
      demographic features. The South Oaks Gambling Screen (SOGS) was used to measure
      pathological gambling and the Symptom Checklist-90-Revised (SCL-90-R) to measure
      psychological distress levels and psychiatric symptoms. Among the 113 enrolled
      subjects we found a greater prevalence of pathological gamblers among drug users
      than among alcoholics and drug abusers were younger than alcoholics; moreover,
      there was a prevalence of single status, low schooling, and a low-medium income
      despite full-time occupation. Only pathological gamblers revealed a significant
      positive correlation with a family history of gambling and reached positive
      scores (>1.5) for some likely psychiatric symptoms. Abuse disorders and
      pathological gambling are frequently associated with multidependence personality
      traits. Preventing substance abuse may reduce the pathological gambling rates and
      better results can be obtained with educational campaigns beginning earlier in
      life.

PMID- 16649513
TI  - [Smoking cessation counselling and dental team].
AB  - The aim of this paper was to present specific strategies to guide dental
      professionals providing smoking cessation interventions. Original papers, reviews
      and current guidelines on this subject, published in English from 2001 to the
      first semester of 2005, were located in the MEDLINE/Pubmed database. Additional
      publications were obtained by searching the reference lists of retrieved studies.
      The "Five A's" strategic approach represents a brief and effective protocol for
      smoking cessation that members of dental team can use with all patients in their
      office practice. Intensive interventions, more effective than brief ones, can be
      further adopted with any smokers willing to make a quit attempt. All patients
      attempting to quit should also be encouraged to use the approved pharmacotherapy
      agents, including nicotine patch, nicotine gum, nicotine inhaler, nicotine nasal
      spray, and bupropion sustained released. These medications significantly increase
      success rates and offer valuable assistance in the reduction of nicotine
      withdrawal symptoms. The evidence presented supports the efficacy of smoking
      cessation counselling by oral health professionals. Dentists and dental
      hygienists, therefore, should be trained on smoking cessation counselling and
      dental offices should incorporate this service into routine patient care.

PMID- 16649514
TI  - [Burnout: rising interest phenomenon in stressful workplace].
AB  - Many stressful situations, particularly strong and long time lasting, can induce
      the burnout syndrome. The definition "burnout" refers to emotional and exhausting
      conditions related to working environment. Since 70'ties, many studies, have
      focused on this topic, have assessed that this condition is much more frequent in
      some particular professional categories: teachers, physicians, nurses, social
      workers, policemen, judges (the so-called helping professions). The main syndrome
      characteristics are: physical and emotional fatigue, depersonalization,
      frustration for unsuccessful professional realization and reduced personal
      accomplishment in competence and productivity with decreasing critical sense
      towards working field. The Maslach Burnout Inventory (MBI) has been the most
      popular instrument for measuring burnout in medical research. The coherence of
      many studies results on helping professions in different countries, leads to the
      conclusion that basically burnout is a psycho-social phenomenon of international
      relevance. These studies have also identified personal, relational and
      environmental risk factors susceptible to prevention.

PMID- 16649515
TI  - [Fine tuning of the many regulations of quality system: the role of the quality
      in the thermal medicine].
AB  - In the last decades, quality has imposed itself as a competitive need for firms,
      and also as a new normative parameter to guarantee the production process and the
      final product which the costumer buys. In the case of health services, the
      importance of quality is even greater because of the special value of this
      service, and the special relationship between the supplier and the
      costumer/patient. This relationship is often mediated by the State which has to
      provide the health services and the financial support for them. Thus, also in the
      case of Thermal Medicine, quality and its certification play a key role for the
      evaluation of the efficiency of the health service, and tend always more to be
      part of the health service accreditation process. In this article, we review the
      development of the idea of quality of service from the ancient Egyptian until the
      20th century and we briefly recall the main European and Italian norms. We also
      examine the norms for the accreditation of the thermal health structures, and we
      review the main indicators of quality in Thermal Medicine, and the role of
      scientific research. Finally, we indicate that the cost of the lack of quality
      can be so prohibitive that the firms which do not follow the new standards, are
      put out of the market.

PMID- 16649516
TI  - [Bladder endometriosis. Report of two cases and bibliographic review, with
      special focus on Spanish articles].
AB  - OBJECTIVES: To study and review the etiopathogenic hypothesis for endometriosis
      and the clinical features, diagnosis and treatment of bladder endometriosis.
      METHODS/RESULTS: We report two cases and review the international bibliography,
      collecting the cases published by Spanish authors. CONCLUSIONS: Bladder
      endometriosis is a rare pathological entity, but its diagnosis should be
      considered in fertile women with urinary tract symptoms during menstruation.
      Diagnosis is obtained by various imaging tests (ultrasound, CT scan, MRI), and is
      confirmed with cystoscopy and biopsy. The treatment may be surgical (TUR, partial
      cystectomy) and/or medical (hormonal).

PMID- 16649517
TI  - [Determination of P53 in infiltrative primary bladder tumors as a prognostic
      factor for understaging].
AB  - OBJECTIVES: To determine if p53 expression in patients with infiltrative bladder
      cancer is a prognostic factor on clinical staging and cancer specific survival.
      METHODS: Immunohistochemical analysis of p53 in 34 patients (33 males and 1
      female) undergoing radical cystectomy for infiltrative bladder cancer, with a
      mean follow-up of 16 months. RESULTS: p53 overexpression was detected in 18
      patients (64%). In the p53 positive group two patients were stage T1G3, 18
      patients T2, 1 patient T3, and 2 patients T4. In the negative group a better
      correspondence between TUR and cystectomy stage was found, with stage worsening
      only in 3 patients. On follow-up, p53 positive patients showed worse outcomes due
      to their worse stages, although no statistical differences were found (p = 0.24).
      In the group of patients following a bladder sparing protocol (n = 6), p53
      negative patients had complete remission of the disease. CONCLUSIONS: We see
      significant differences on understaging/more aggressive local outcome in p53
      positive patients, with no greater mortality in this group. P53 expression does
      not contraindicate the inclusion of a patient in a bladder sparing protocol,
      although larger studies would be necessary to confirm these results.

PMID- 16649518
TI  - [Preoperative prognostic variables in renal cancer].
AB  - OBJECTIVES: To analyze the correlation between preoperative variables in patients
      with kidney cancer and subsequent finding of bad prognosis factors. METHODS:
      Retrospective cohort study reviewing the charts of all patients undergoing
      surgery at the HIBA bet- ween June 1988 and April 2003. 555 patients were
      included, registering age, gender, and clinical presentation. Pathology reports
      were classified following WHO for histology, Furhman for tumor grade, and AJCC
      for tumor stage. Intrarenal disease was defined as tumors < or = T2; the rest of
      the tumors were considered extrarenal. Statistical analysis was performed using
      the Statistic 7 Software, performing Students t test, proportions comparison
      test, chi-square test, and odds ratio. RESULTS: Mean age was 58.8 years (r: 20
      94), 388 (69.9%) patients were males and 167 (30.1%) females. 209 (37.7%) were
      smokers or ex-smokers. 256 (46.1%) tumors were incidentally diagnosed, 299
      (53.9%) were symptomatic. The right kidney was affected more often (54.6%), and
      2.3% were bilateral synchronic tumors. Grade II was the most frequent grade
      (62.2%). T1 was the predominant TNM with 273 patients (49.2%). Mean tumor size
      was 6.7 cm, with 5.54 cm for the intrarenal tumors and 8.67 cm for the extrarenal
      (Student t test p < 0.00001). 49.6% (127) of the 256 asymptomatic patients have
      extrarenal tumors, in comparison with only 26.4% (79) of the 299 symptomatic
      patients (chi-square p < 0.00001). Ninety-two (44%) of the 209 smokers had
      extrarenal tumors in comparison with 114 (32.9%) of the non-smokers. CONCLUSIONS:
      We may say that patients having a symptomatic renal tumor have between 2 and 3
      times more probability to have non organ-confined disease at the time of surgery
      This also increases, although in smaller amounts, between smokers and older than
      70 years patients. The presence of a tumor greater than 7 cm almost triplicates
      of the possibility of extrarenal involvement.

PMID- 16649519
TI  - [Tobacco consumption and bladder cancer mortality in Spain].
AB  - OBJECTIVES: To establish the trend of the bladder cancer adjusted mortality and
      its correlation with tobacco consumption in different Spanish Autonomic
      Communities over a 15 year period. METHODS: We evaluate the trends of mortality
      rates associated with bladder cancer between January 1st 1989 and December 31st
      2002 in the geographic area of Spain, as well as the tendency of tobacco
      consumption. Demographic and mortality data were obtained from the National
      Institute of Statistics, and consumption data were obtained from the Commissioner
      for the Tobacco Market in the Spanish Economics and Finances Ministry. We
      calculate the average number of cigarettes (1 package = 20 cigarettes) consumed
      per person; we also calculate bladder cancer adjusted mortality rates, presented
      as number of deaths for that cause per 100.000 persons year, and the ratio
      between number of packages of cigarettes consumed and adjusted mortality rate. We
      determine the yearly percentage increase over the whole period of study for both
      the mortality rate and tobacco consumption, and evaluate their correlation by the
      Spearman's coefficient. RESULTS: Mean adjusted bladder cancer mortality rate over
      the period of study was 9.4 deaths per 100.000 habitants year, and mean tobacco
      consumption was 109.7 packages per person year. There has been a 2.05% yearly
      increase of bladder cancer associated mortality, mean cigarette consumption has
      diminished 1.3% per year. The Spearman's test did not show any correlation
      between both factors (p = 0.722). CONCLUSIONS: Despite preventive measures for
      tobacco addiction in our country, there is an important continuous consumption.
      The increase in the incidence of bladder cancer does not seem to be related with
      higher tobacco consumption currently, therefore it may be related with other
      genetic or environmental factors.

PMID- 16649520
TI  - [Papillary and cavitary monohydrate calcium oxalate lithiasis: comparative study
      of etiological factors].
AB  - OBJECTIVES: The monohydrate calcium oxalate lithiasis (MCO) is divided in two
      groups depending on the morphologic-crystal structure: papillary (anchorage point
      on a renal papilla lesion) and cavity (formed in a cavity with low urodynamic
      capacity). The minimal differences between urinary biochemistry of MCO makers in
      comparison with healthy population suggests that other factors different than
      urine biochemistry (professional activity, dietetic habits, systemic diseases)
      may be related with lithogenesis. The objective of this work is to study such
      factors, and compare them in both groups of MCO lithiasis (papillary and cavity).
      METHODS: We study 40 patients with MCO lithiasis (20 patients papillary and 20
      patients cavitary). Medical history was performed (family history of lithiasis;
      associated diseases such as high blood pressure, diabetes, hyperuricemia,
      hypercholesterolemia, peptic ulcer disease; dietetic survey to evaluate phytate
      consumption; professions with high-risk of exposure to toxic agents); 24-hour
      urine biochemical tests, two-hour urine (pH), and serum biochemical profile were
      performed. Statistical analysis was performed using student's t test and chi
      square. RESULTS: There is a high prevalence of family history of renal lithiasis
      (45%) without differences between groups. There are not differences in urine or
      blood biochemical tests. There is a low consumption of phytate-containing foods
      in both groups, without significant differences. There is a trend to a greater
      exposure to cytotoxic agents in the papillary group (45%) vs. the cavity group
      (25%). Hypertension and hyperuricemia are more prevalent in the cavity MCO group
      (alpha = 0.025 and alpha = 0.010, respectively). Peptic ulcer disease is more
      prevalent in the papillary MCO group (alpha = 2.025). There are no significant
      differences in prevalence of hypercholesterolemia or diabetes mellitus between
      groups. CONCLUSIONS: Papillary MCO calculi are associated with a deficit of
      crystallization inhibitors (phytates), and disorders of the epithelium covering
      the renal papilla (cytotoxic agents exposure, peptic ulcer disease). Cavity MCO
      calculi are associated with a deficit of crystallization inhibitors (phytates)
      and a greater amount of heterogeneous nucleants (organic material induced by
      diseases such as hypertension, hyperuricemia, hyperglycemia, and
      hypercholesterolemia).

PMID- 16649521
TI  - [Vesicoureteral reflux grades III-IV: factors involved in the efficacy of
      endoscopic treatment in pediatric patients].
AB  - OBJECTIVES: Vesicoureteral reflux (VUR) is detected in 30-50% of pediatric
      patients diagnosed of urinary tract infection (UTI). Multiple clinical trials
      have compared the results of conservative management against surgical therapy.
      The introduction of a third alternative in 1984 (endoscopic approach) has
      dramatically modified the management of VUR. The objective of our work is to
      analyze the factors influencing the favourable outcome of the endoscopic
      treatment of VUR. METHODS: Retrospective and prospective cohort study analyzing
      90 patients with grades III and IV VUR treated endoscopically over the last eight
      years. 184 patients undergoing endoscopic management were selected from a group
      of 550 patients (735 VUR renal units) with the diagnosis of VUR over the study
      period. All patients underwent VCUG or galactose-based sonocystography to obtain
      the diagnosis. DMSA scintigram was used to evaluate renal damage. Data about
      gender, age, UTI, bilateralism, renal damage, voiding dysfunction, outcomes,
      complications, and recurrences were registered. A new factor was defined:
      ureteral dilation independent from the international classification. This factor
      was evaluated by a single pediatric urologist blinded for the international
      classification results. Data analysis was performed using the chi square test and
      Fischer exact test; a multiple logistic regression analysis was also performed.
      Statistical significance was established at p < 0.05. SPSS 11.0 software was
      employed for data analysis. RESULTS: Boys/girls ratio was 2.91. Bilateral VUR
      appeared in 44.4% of the cases. UTI was the presenting diagnosis in 64 cases; the
      diagnosis was prenatal in 21 cases (with a male predominance 5.2:1). We found a
      strong correlation between renal scarring at the time of diagnosis and voiding
      dysfunction (p< 0.01). Cure rate after first injection was 64%. Although
      univariate analysis showed a strong correlation between cure and first injection,
      biloterality, voiding dysfunction, initial nephropathy, and ureteral dilation
      grade, on multivariate logistic regression the only significant factor to predict
      treatment response was the existence of severe ureteral dilation in comparison
      with mild dilation (p < 0.001; odds ratio 0.045, 95% confidence interval 0.01
      0.16). Renal damage progression was specially detected in those patients with
      voiding dysfunction (p = 0.053), bilaterality (p = 0.034) and severe ureteral
      dilation (p < 0.001). CONCLUSIONS: A direct relation between cure rate after
      endoscopic treatment of grade III and IV reflux and severity of ureteral dilation
      was demonstrated. Other relevant factors implied in the endoscopic resolution of
      VUR include the existence of voiding dysfunction, bilateral reflux and renal
      damage determined by DMSA at the time of initial diagnosis. Gender, age, and
      number of infections during follow up have no influence in the probability of
      cure of grade III and IV VU reflux treated with subureteral injection of
      biocompatible substances.

PMID- 16649522
TI  - [Spanish registry of the TRT Reemex system in women with stress urinary
      incontinence (SUI)].
AB  - OBJECTIVES: Due to the absence of randomized studies, the Spanish Reemex Working
      Group started a registry to analyze and review the results of a large group of
      patients with mid-term and long-term follow-up to obtain conclusions based on
      clinical experience. METHODS: A registry of 715 patients who underwent surgical
      intervention for insertion of the SUI readjustable prosthesis Reemex TRT (tension
      free readjustable tape) in 15 Spanish hospitals (40% urology departments, 60%
      gynecology departments). The registry was established to evaluate the safety and
      efficacy of the sling adjustability concept in the surgical treatment of female
      SUI. The Spanish Working Group was able to evaluate results of the Reemex system
      in 683 patients of a total of 715. Mean age was 59.9 yr (range 21-87) with a mean
      follow-up of 23 months (6-93). The group includes: 30.2% patients with mixed
      incontinence, 73.1% patients with urodynamic intrinsic sphincteric deficit, 35.7%
      patients with previous history of failed surgical interventions for urinary
      incontinence, and 54.3% previous pelvic floor associated operations. All patients
      were evaluated preoperatively with history, physical examination and urinary
      incontinence questionnaire. Each follow-up visit included incontinence
      questionnaire, physical examination and stress test. RESULTS: Cure rate was
      92.2%, with 6.9% improvement and 0.9% failures. Readjustment was performed in 416
      patients (60.9%) as a second phase of surgery over the following 24-48 hours,
      before hospital discharge. 80 patients (11.7%) were readjusted in the mid- or
      long-term (between 6 and 8 months after surgery). The level of support of the
      sling was successfully reduced in three patients between 6 and 14 months after
      surgery. No other patient suffered voiding difficulties in the long-term. 1.7% of
      the patients needed extraction of the tensor due to persistent abdominal wall
      seroma. 0.8% presented vaginal extrusion of the sling. CONCLUSIONS: The Reemex
      system is a minimally invasive technique with consistent results and even
      improved in heterogeneous groups of patients including intrinsic sphincter
      defficiency, reoperations, mixed incontinence and associated pathologies.

PMID- 16649523
TI  - [Laparoscopic pyelolithotomy].
AB  - The application of laparoscopy as a surgical technique in Urology has enabled to
      expand the therapeutic options for various pathologies. The treatment of urinary
      lithiasis localized in the renal pelvis is one of them. We report a laparoscopic
      pyelolithotomy, describing the operation step-by-step, from patient positioning
      and trochar insertion to drainage tube insertion and closure. The objective of
      this article is to show the technique, presenting it as an alternative option.

PMID- 16649524
TI  - [Partial testicular feminization syndrome].
AB  - OBJECTIVES: To report one case of partial androgen insensitivity syndrome.
      METHODS: The patient underwent history and physical examination, blood tests,
      hormone determinations, androgen stimulation and suppression tests, nuclear
      chromatin and karyotype, imaging and endoscopic tests, exploratory laparoscopy
      with gonadal biopsy and bilateral orchyectomy, and subsequent genital plasty.
      RESULTS: We report the case of a phenotypically female patient with genital
      ambiguity, with a dorsally curved peniform clitoris and a urogenital sinus with
      partial labia fusion. Blood tests, hormonal determinations, and androgen
      stimulation-suppression tests were all normal. Both ultrasound and laparoscopy
      showed absence of internal genitalia. The biopsy showed testicles with relative
      Leydig cell hyperplasia and slight basal membrane thickening. The cosmetic and
      functional results were completely satisfactory with normal sexual intercourse.
      CONCLUSIONS: The reinforcement of the generic role after genital plasty provided
      satisfactory identification and sexual performance.

PMID- 16649525
TI  - [Inverted papilloma of the anterior male urethra. Case report and bibliographic
      review].
AB  - OBJECTIVES: We report a clinical case of inverted papilloma of the anterior male
      urethra. METHODS/RESULTS: 40-year-old male without significant past medical
      history presenting with dysuria and referring three episodes of urethral
      bleeding. Preliminary studies included voiding cystourethrogram (VCUG) which
      revealed a filling defect in the anterior urethra. Urethrocystoscopy was
      performed under anesthesia, with resection of the tumor. Pathologic study
      reported a urethral inverted papilloma. CONCLUSIONS: Inverted papillomas of the
      male urethra are rare. The most frequent clinical manifestations are dysuria and
      hematuria, although they may present with urethral bleeding when located in the
      anterior urethra. Diagnosis is based on clinical symptoms, ultrasound, endoscopy
      and VCUG which enable detection of urethral filling defects. The treatment of
      choice is transurethral resection of the lesion. Annual endoscopic control is
      recommended after surgery.

PMID- 16649526
TI  - [Solitary fibrous tumor of the tunica vaginalis testis].
AB  - OBJECTIVES: We report one case of solitary fibrous tumor of the tunica vaginalis,
      a benign paratesticular lesion. METHODS: Surgical exploration with intraoperative
      biopsy and excision of the lesion was undertaken, leaving the testicle and
      epididymis undamaged. RESULTS: Intraoperative biopsy revealed the presence of
      fibrous tissue without malignant cellularity. Pathological diagnosis on the
      surgical specimen was solitary fibrous tumor of the tunica vaginalis. The patient
      remains asymptomatic and disease-free one year after treatment. CONCLUSIONS:
      Almost all testicular masses are malignant, but in order to avoid a non-indicated
      orchyectomy, one should be cautious with the finding of a paratesticular lesion
      of probable benign nature on ultrasound or during surgery.

PMID- 16649527
TI  - [Neurosyphilis and bladder dysfunction].
AB  - OBJECTIVES: Syphilis is a systemic disease the course of which follows successive
      clinical stages. Central nervous system and spinal cord involvement on late
      phases may lead to bladder dysfunction. We report one case of neurosyphilis with
      associated bladder hyperreflexia. METHODS/RESULTS: 51-year-old male with the
      diagnosis of neurosyphilis consulting for voiding disorders with evidence of
      detrusor hyperactivity of neurogenic etiology on the urodynamic study.
      CONCLUSIONS: The differential diagnosis of neurogenic bladder in patients with
      psychiatric or neurological symptoms should include neurosyphilis. Etiologic
      diagnosis is obtained by cerebrospinal fluid examination, and the diagnosis of
      bladder dysfunction by urodynamic study.

PMID- 16649528
TI  - [Ureteral endometriosis. Case report].
AB  - OBJECTIVES: Ureteral endometriosis is a rare entity which may produce urinary
      tract obstruction with subsequent loss of renal function if treatment is not
      undertaken early due to its asymptomatic but locally aggressive course.
      METHODS/RESULTS: We report one case of intrinsic ureteral endometriosis with
      unilateral renal failure (renal atrophy) and unresectable periureteral
      fibroinflammatory thickening involving vascular or visceral structures.
      CONCLUSIONS: We emphasize the diagnostic and therapeutic importance of a high
      degree of clinical suspicion about this entity, mainly in patients with history
      of genital endometriosis.

PMID- 16649529
TI  - [Solitary pararenal fibrous tumor].
AB  - OBJECTIVES: To report a rare clinical case of solitary pararenal fibrous tumor,
      analyzing its pathological characteristics and prognosis by a bibliographic
      review. METHODS/RESULTS: We present the case of a 36-year-old male consulting for
      right flank colic pain, which was diagnosed of a solid mass in the lower pole of
      the right kidney and underwent right radical nephrectomy. Pathological study of
      the surgical specimen showed the presence of a solitary pararenal fibrous tumor.
      CONCLUSIONS: Solitary fibrous tumor is a rare neoplasia, being its pararenal
      localization even rarer. It is a tumor with benign behavior in up to 90% of the
      cases. The immunohistochemical study is the key to diagnosis.

PMID- 16649530
TI  - [Bladder leiomyosarcoma: case report].
AB  - OBJECTIVES: To report a new case of bladder leiomyoma in an adult. METHODS: 64
      year-old female patient consulting for a four-month hematuria diagnosed of a
      bladder intraluminal tumor on ultrasound during a routine gynecologic revision.
      Cystoscopy confirmed the presence of the tumor. Transurethral resection was
      indicated. RESULTS: Pathology reported a definitive diagnosis of leiomyosarcoma.
      Anterior pelvic exenteration was subsequently performed. On one year follow-up
      there is no evidence of disease. CONCLUSIONS: We emphasize the rarity of these
      neoplasias. We comment on their main characteristics, pointing out the importance
      of immunohistochemical staining for the definitive histological diagnosis. We
      refer the therapeutic options described in the literature.

PMID- 16649532
TI  - Sarcomatoid chromophobe renal cell carcinoma. A case report and review of the
      literature.
AB  - OBJECTIVES: We report herein the clinical, histological, and immunohistochemical
      features of a case of sarcomatoid chromophobe renal cell carcinoma.
      METHODS/RESULTS: A 59-year-old woman referred a two-month history of constant
      right flank pain, and hematuria. A right radical nephrectomy was performed. Gross
      pathologic examination showed a tumor located in the lower part of the kidney
      with two different aspects. Histologically, the tumor was composed of two
      intermixed distinct morphologic components: a chromophobe renal cell carcinoma
      and a high-grade spindle cell sarcoma. CONCLUSION: Our case represent a typical
      sarcomatoid chromophobe cell carcinoma. This unusual renal cancer has the
      potential to behave aggressively and to metastasize.

PMID- 16649533
TI  - Beta3-adrenergic stimulation in the human heart: signal transduction, functional
      implications and therapeutic perspectives.
AB  - Next to beta1- and beta2-adrenoceptors, a third beta-adrenoceptor population is
      expressed in the human heart, the beta3-adrenoceptor. In mammalian ventricular
      myocytes, beta3-adrenergic stimulation leads to a decrease in contractility via a
      release of nitric oxide (NO). Recently, different molecular mechanisms of beta3
      adrenergic activation of endothelial nitric oxide synthase (eNOS) have been
      uncovered in cardiac myocytes. In the non-failing and especially the failing
      heart, beta3-adrenergic stimulation may offer protection against excessive
      catecholaminergic beta1-adrenoceptor stimulation. In this context, the beta3
      adrenoceptor is discussed as a novel target for the pharmacological therapy of
      heart failure.

PMID- 16649534
TI  - Oligopyrrole carboxamides linked with a nucleobase as potential DNA minor groove
      binding ligands: synthesis, DNA binding and biological evaluation.
AB  - The synthesis of a series of new oligopyrrole carboxamides closely related to
      netropsin and distamycin A, linked with a nucleobase is reported. The new
      compounds possess similar structure elements as the known peptide nucleic acids
      which are interesting sequence reading DNA ligands. Cytotoxicity in vitro, the
      DNA binding characteristics and the inhibition of topoisomerase I were studied.
      Four of the compounds, 27, 31, 33 and 37 bind to DNA probably at AT sequences
      like netropsin or distamycin A in the minor groove. Surprisingly, no cytotoxicity
      and no inhibition of topoisomerase I was found.

PMID- 16649535
TI  - New tacrine-hydrazinonicotinamide hybrids as acetylcholinesterase inhibitors of
      potential interest for the early diagnostics of Alzheimer's disease.
AB  - The syntheses and the preliminary results of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) inhibition by an affinity series of tacrine
      hydrazinonicotinamide hybrids are described. These molecules were prepared by
      condensation of tacrine analogues with the hydrazine nicotinate moiety (HYNIC).
      Derivatives 6a and 6b showed lower activity than the model tacrine, while
      compounds 6c and 6d showed the strongest affinity to AChE. All the tested
      compounds exhibited lower affinity for BChE than tacrine. Alzheimer disease (AD)
      is characterised by a deficit of acetylcholinesterase, and these new compounds,
      as ligands for 99mTc complexes, are potential radiopharmaceuticals for an early
      diagnosis of Alzheimer's disease.

PMID- 16649536
TI  - Synthesis, anti-HIV and antitubercular activities of isatin derivatives.
AB  - HIV is the most significant risk factor for many opportunistic infections like
      tuberculosis. In this study, we designed an isatinimino lead compound as a novel
      non-nucleoside reverse transcriptase inhibitor with antimycobacterial properties
      for the effective treatment of AIDS and AIDS-related tuberculosis. Among the
      compounds sythesized, 1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-7[[N4
      [3'-[(4,6-dimethylpyrimidin-2-yl)benzenesulfonamido-4-yl]imino-1'-(5
      fluoroisatinyl)]methyl]-3-methyl N1-piperazinyl]-3-quinoline carboxylic acid (9)
      emerged as the most potent broad-spectrum chemotherapeutic agent active against
      HIV (EC50: 12.1 microg/ml), and Mycobacterium tuberculosis (MIC: 1.22 microg/ml).

PMID- 16649537
TI  - [Thieno[3,2-c]quinoline-4-yl-amines--synthesis and investigation of activity
      against malaria].
AB  - Thieno[3,2-c]quinoline-4-yl-amines - synthesis and investigation of activity
      against malaria pH-Dependant reduction of the methyl 2-(2-nitrophenyl)thiophene-3
      carboxylate 3, formed by Suzuki coupling of methyl 2-iodothiophene-3-carboxylate
      (2) with 2-nitrophenylboronic acid, yielded the cyclic hydroxamic acid 4 and the
      lactam 5, respectively. The 4-chlorothieno[3,2-c]quinoline 6 was formed from the
      lactam 5 by heating with POCI3/PCI5s. Melting of 6 with the novaldiamine base in
      phenol gave the chloroquine analogue 7, whereas the amodiaquine and the
      pyronaridine analogues 8 and 9 were obtained using phenol Mannich bases. The
      reaction of 6 with putrescine and N,N'-bis(3-aminopropyl)piperazine as spacer
      formed the bisquinoline derivatives 10 and 11 as well as the monosubstituted
      quinoline 12. In the same manner the isomeric 4-chlorothieno[2,3-c]quinoline 13
      reacted to yield the quinoline-4-yl-amines 14-16. The compounds 7-12 and 14-16
      were tested for in vitro growth inhibition of the malaria parasite Plasmodium
      falciparum. As most active compound the pyronaridine derivative 9 displayed an
      IC50 value of 210 nM with the chloroquine sensitive P. falciparum strain 3D7 and
      750 nM with the chloroquine resistant P. falciparum strain Dd2. The N,N'-bis(3
      aminopropyl)piperazine derivative 11 displayed in vivo activity in Plasmodium
      vinckei infected mice with an ED50 value of 30 mg/kg after i.p. administration.

PMID- 16649538
TI  - Determination of the antihyperlipidemic simvastatin by various voltammetric
      techniques in tablets and serum samples.
AB  - The electrochemical behavior and determination of simvastatin (SMV), a lipid
      lowering drug, were studied in aqueous alcohol medium at a stationary glassy
      carbon electrode. Cyclic voltammetry studies showed one main, well-defined, sharp
      oxidation peak between pH 2 and 8. The oxidation was irreversible and exhibited a
      diffusion controlled mechanism. Differential pulse and square wave voltammetric
      methods for the quantitative determination of SMV in pharmaceutical dosage forms
      and spiked serum samples were developed based on the linear relationship between
      the peak current and the concentration. Differential pulse and square wave
      voltammetric techniques for the determination of SMV in 0.1 M H2SO4 and a
      constant amount of methanol (20%), which allow quantitation over the 2 x 10(-6)-1
      x 10(-4) M range in supporting electrolyte with a detection limit of 2.71 x 10(
      7) M and 5.50 x 10(-7) M for differential pulse and square wave voltammetric
      methods, respectively, are proposed. The repeatability and reproducibility of the
      methods were determined. Precision and accuracy were also checked. These methods
      were used for the determination of SMV in tablets. The standard addition method
      was used in biological media. No electroactive interferences from endogenous
      substances and excipients were found in biological fluids and pharmaceutical
      dosage forms, respectively.

PMID- 16649539
TI  - Voltammetric studies of sparfloxacin and application to its determination in
      pharmaceuticals.
AB  - A detailed study of the electrochemistry of sparfloxacin at a glassy carbon
      electrode was carried out in the pH range 2.0-10.0 in aqueous solution using
      cyclic and differential pulse voltammetry. Influence of different supporting
      electrolytes, pH, scan rate and concentrations were studied on the voltammetric
      response. The studies revealed the irreversible oxidation of sparfloxacin at
      basic pH in a diffusion controlled manner. In addition, a differential pulse
      voltammetric method was proposed for the determination of the drug in different
      pharmaceutical formulations.

PMID- 16649540
TI  - Protein rejecting properties of PEG-grafted nanoparticles: influence of PEG-chain
      length and surface density evaluated by two-dimensional electrophoresis and
      bicinchoninic acid (BCA)-proteinassay.
AB  - Poly (ethylene glycol) (PEG)-grafted nanoparticles have been described as
      potential intravenously injectable, long-circulating drug carriers. The in vivo
      behaviour of intravenous administered nanoparticles is decisively influenced by
      the interaction of the particles with the blood proteins. Two-dimensional
      electrophoresis (2-DE) was employed to study the protein rejecting properties of
      PEG-grafted polymer nanoparticles, possessing PEG-200 and PEG-400 chains,
      respectively. The calculated PEG-chain distances varied between 0.39/0.31 nm (PEG
      200) and 0.39/0.34 nm (PEG-400), therefore it was possible to study the influence
      of high chain densities attained by the use of short PEG chains on the protein
      adsorption. Apart from a stronger protein rejection of small-MW proteins achieved
      by PEG-chain distance diminution, the affinity of several proteins for the PEG
      chains are shown and discussed. Beside the study of protein adsorption patterns,
      the total protein mass adsorbed to the particles, as well as the extent of
      protein desorption prior to 2-DE, was investigated using the bicinchoninic acid
      (BCA)-protein assay.

PMID- 16649541
TI  - Branched-chain alkanols as skin permeation enhancers: quantitative structure
      activity relationships.
AB  - One long-standing approach for improving transdermal drug delivery is using
      penetration enhancers which reversibly decrease the skin barrier resistance.
      Though the skin permeation enhancement effect of chemical penetration enhancers
      has been studied extensively, their quantitative structure-activity relationships
      have not been adequately investigated. In this paper, we established the
      correlation equations between enhancement potencies and the physico-chemical
      parameters relevant to lipophilicity and position of hydroxyl group for 16
      alkanols using the stepwise multiple linear regression analysis. These equations
      reveal that the enhancement potencies of alkanols are excellently correlated with
      their lipophilicity and position of the hydroxyl group. The enhancement potency
      of an alkanol will increase when it has greater lipophilicity but will decrease
      as the hydroxyl group moves from the end of the alkyl chain towards the center.

PMID- 16649542
TI  - Low molecular weight quaternised chitosan (11): in vitro assessment of absorption
      enhancing properties.
AB  - N-Trimethyl chitosan chloride (TMC; high molecular weight) and N-trimethyl
      chitosan oligosaccharide (TMO; low molecular weight) with different degrees of
      quaternisation were synthesised and evaluated for their absorption enhancing
      properties across mucosal epithelia. These quaternised chitosan derivatives
      (0.0625% w/v-0.5% w/v) showed a significant decrease in the transepithelial
      electrical resistance (TEER) of cultured rabbit tracheal epithelial cell
      monolayers as compared to the control. The degree of quaternisation and
      concentration of the compounds influenced the extent of the reduction in TEER.
      Higher degrees of quaternisation and an increase in the concentration of the
      compound were associated with a more pronounced reduction in the TEER. The TMO
      derivatives seemed to be more effective in lowering the TEER of tracheal cell
      monolayers as compared to the TMC polymers. Ciliary beat frequency (CBF) is the
      main defence mechanism of the respiratory tract and is therefore a useful
      parameter in evaluating the toxicity of nasally administered drugs and additives.
      The effect of the synthesised chitosan derivatives on the CBF of human nasal
      epithelial cells at pH 7.4 was determined by a method based on an analogue
      contrast enhancement technique. The TMO oligomers exhibited lower inhibition of
      the CBF of human nasal epithelial cells compared to that of the TMC polymers. It
      was proposed that this reduced effect on the CBF is due to the lower viscosity
      and molecular weight of TMO. However, no acute toxicity was found with any of the
      synthesised chitosan derivatives by means of the CBF tests conducted in this
      study.

PMID- 16649543
TI  - Application of novel chitosan derivatives in dissolution enhancement of a poorly
      water soluble drug.
AB  - Solid dispersions of the poorly water soluble drug dexamethasone and newly
      synthesized chitosan derivatives (chitosan succinate, CS, and chitosan phthalate,
      CP) were prepared by spray drying. The resulting microspheres were evaluated in
      terms of their drug loading or encapsulation efficiency as well as drug release
      profile. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD)
      and infrared spectroscopy (IR) were used to evaluate the solid dispersion for
      possible interactions between drug and polymers. The pure drug was evaluated in
      the same manner for comparison purposes. High loading levels (>74%) were achieved
      using CP and CS as polymer matrices. Drug release rate was accelerated
      significantly upon the formation of the solid dispersions; the drug release rate
      was increased with increasing percentage of the chitosan derivatives in the
      microspheres. IR studies showed no chemical interaction while the X-ray studies
      showed a significant change in the crystallinity of the drug upon formation of
      solid dispersions.

PMID- 16649544
TI  - Effect of PEG2000 on drug delivery characterization from solid lipid
      nanoparticles.
AB  - The purpose of this work is to develop a PEG2000-modified solid lipid
      nanoparticles (SLN) intended to encapsulate a drug within their matrix and to
      study their characteristics. In the present report, drug-loaded SLN were prepared
      by a novel solvent diffusion method in an aqueous system. Monostearin and PEG2000
      were used as carrier material and modifying agent, respectively. The model drug
      salbutamol sulphate was incorporated to study the characterization of entrapment
      efficiency, size, zeta potential (charge) and drug delivery characterization. In
      the test solution of pH 7.2 phosphate buffer, drug-release behavior from SLN
      suspension exhibited a biphasic pattern. With the monoastearin-based SLN, a
      distinctly prolonged release over a monitored period of 14 days was observed
      after a burst drug release in the first 8 hours. Over the monitored period of
      prolonged release, there was delayed release in the first 5 days with nearly
      2.51% of the drug released each day, following which a slightly higher release
      rate (8.14% per day) appeared in the last 9 days. In contrast, the drug release
      rate from PEG2000-modified SLN was faster. Nevertheless, further work is required
      in order to optimize the release behavior of various entrapped drugs. These
      results also demonstrate that modification with PEG2000 can accelerate release of
      hydrophilic small molecule drugs from SLN.

PMID- 16649545
TI  - Influence of selected tensides on the hydrocortisone concentration equilibrium
      balance in micelles and the dispersing center.
AB  - The degree of hydrocortisone binding, was investigated by means of equilibrium
      dialysis in the presence of 1% or 3% micellar solutions of polysorbate 20 and 80.
      Stabilization of the concentration equilibrium was found in all the cases
      investigated. The degree of hydrocortisone binding in micelles depends on the
      concentration and type of tenside used.

PMID- 16649546
TI  - Solubility prediction of salicylic acid in water-ethanol-propylene glycol
      mixtures using the Jouyban-Acree model.
AB  - To show the applicability of a solution model, i.e. the Jouyban-Acree model, for
      predicting the solubility of a solute in ternary solvent systems based on model
      constants computed using solubility data of the solute in binary solvent systems,
      the solubility of salicylic acid in water-ethanol, water-propylene glycol,
      ethanol-propylene glycol mixtures was determined. A minimum number of three data
      points from each binary system was used to calculate the binary interaction
      parameters of the model. Then the solubility in other binary solvent compositions
      and also in a number of ternary solvents was predicted, and the mean percentage
      deviation (MPD) was calculated as an accuracy criterion. The overall MPD (+/-SD)
      was 7.3 (+/-7.3)% and those of a similar predictive model was 15.7 (+/-11.5)%.
      The mean difference between the proposed and a previous model was statistically
      significant (paired t-test, p < 0.004).

PMID- 16649547
TI  - Solubilization of valsartan by aqueous glycerol, polyethylene glycol and micellar
      solutions.
AB  - To increase the solubility of valsartan in aqueous solutions was considered of
      interest. This study therefore investigated the solubilization of valsartan by
      cosolvency and micellization. Of the solubilization agents used, sodium lauryl
      sulfate was found to be the most effective. The increase in solubility at the
      maximum concentration studied was in the following order: sodium lauryl sulfate >
      polysorbate-80 > polyethylene glycol 400 > glycerol. The effect of propylene
      glycol on the solubility of valsartan in a 2% w/v polysorbate-80 solution was
      also investigated and was found that propylene glycol decreased the solubilizing
      power of polysorbate-80 at the concentrations studied.

PMID- 16649548
TI  - Spray-dried propolis extract. I: physicochemical and antioxidant properties.
AB  - The effect of spray drying on the chemical and biological properties of alcoholic
      extract of green propolis was investigated. The total polyphenol and flavonoid
      contents in spray-dried propolis extract were determined by the Folin-Ciocalteu
      and aluminum chloride colorimetric methods, respectively. The antioxidant
      activity of the dry extract was assessed by the membrane lipid peroxidation
      inhibition method, using quercetin as reference. The polyphenol content was shown
      to depend on the drying air outlet temperature and its square at the 0.5%
      significance level, while the flavonoid content depended only on the square of
      the outlet temperature at the 5% significance level. Polyphenol and flavonoid
      recovery after spray-drying ranged from 45.1 to 54.9% and 30.6 to 40.8%,
      respectively. The antioxidant activity of the spray-dried propolis was shown to
      be affected by the extract feed rate and air outlet temperature at a significance
      level of 0.1%. The spray-dried propolis extract showed significant antioxidant
      activity, with 50% lipid peroxidation inhibition at concentrations ranging from
      2.5 to 5.0 microg/ml.

PMID- 16649549
TI  - Comparison of the percutaneous absorption of hydrophilic and lipophilic compounds
      in shed snake skin and human skin.
AB  - The in vitro transdermal permeation of eight hydrophilic drugs (antipyrine, L
      dopa, dopamine hydrochloride, diclofenac sodium, 5-fluorouracil, isoprenaline
      hydrochloride, nicorandil and morphine hydrochloride) and eight lipophilic drugs
      (aminopyrine, cyclobarbital, ibuprofen, indomethacin, isosorbide dinitrate,
      flurbiprofen, ketoprofen and lignocaine) was determined using shed snake skin of
      Elaphae obsoleta and human skin. The permeation parameters and physiological
      characteristics of the skin, e.g. the water and lipid content, and the thickness
      of shed snake skin and human skin were evaluated and compared. In shed snake
      skin, the permeability coefficients (P) of lipophilic drugs were in the same
      range as those through the human skin (0.9 to 1.8-times); whereas those of
      hydrophilic drugs were remarkably lower (3.3 to 6.1-times). The thickness and
      lipid content of shed snake skin and human stratum corneum were not significantly
      different (P > 0.05), whereas the water content of shed snake skin was
      significantly lower than that of human stratum corneum (P < 0.05). The lower
      permeability of shed snake skin for hydrophilic compounds might be caused by the
      lower porosity of skin strata. The results suggested a potential use of shed
      snake skin as barrier membrane for lipophilic compounds percutaneous absorption
      studies in vitro.

PMID- 16649550
TI  - Comparison of high sensitivity micro differential scanning calorimetry with X-ray
      powder diffractometry and FTIR spectroscopy for the characterization of
      pharmaceutically relevant non-crystalline materials.
AB  - In this study, high sensitivity micro differential scanning calorimetry (MDSC) in
      the scanning of dynamic mode was compared to X-ray powder diffractometry (XRPD)
      for quantifying amorphous nifedipine in mixtures crystalline nifedipine. This
      technique was also compared with FTIR for quantifying polymorph A of
      chloramphenicol palmitate (CAP) and poly DL-lactide-co-glycolide) (PLGA) in
      pharmaceutical formulations. The limit of determination (LOD) achieved by MDSC
      were 0.06% compared to 5% for XRPD quantification of amorphous nifedipine and
      0.02% compared to 7% for IR quanitfication of polymorph A of CAP. As little as
      0.165 mg PLGA could be measured in excipients mixtures. Desirable linearity and
      repeatability were established in all cases.

PMID- 16649551
TI  - ACEA (arachidonyl-2-chloroethylamide), the selective cannabinoid CB1 receptor
      agonist, protects against aspirin-induced gastric ulceration.
AB  - The effect of a selective cannabinoid CB1 receptor agonist, ACEA (arachidonyl-2
      chloroethylamide) in an aspirin-induced ulcer model was studied in rats. ACEA
      (1.25-5 mg/kg i.p.) significantly reduced gastric ulcer formation to 24, 21 and
      0.6% respectively. These results confirm the cytoprotective effect of CB1
      receptor agonists and suggest that the endocannabinoid system might be the target
      for a novel class of anti-ulcer drugs.

PMID- 16649552
TI  - In vivo immunomodulatory profile of telithromycin in a murine pneumococcal
      infection model.
AB  - In addition to bactericidal activity, macrolide antibacterials possess clinically
      relevant properties such as immunomodulatory activity. Whether such activity
      extends to novel antibacterials that are structurally related to macrolides, such
      as the ketolides, remains largely unknown. The objective of this study was to
      evaluate the in vivo immunomodulatory profile of the first ketolide antibacterial
      - telithromycin in a murine neutropenic thigh infection model. Specific pathogen
      free, female ICR mice were rendered transiently neutropenic with intraperitoneal
      cyclophosphamide. Thighs were inoculated with 10(6) colony-forming units of a
      single clinical isolate of Streptococcus pneumoniae. Once inoculated, mice
      (n=500) received single oral doses of telithromycin (10, 25 or 50 mg/kg of body
      weight) or no treatment (control). Blood was obtained via cardiac puncture prior
      to and at 2, 4, 8, and 24 h after dose administration for determination of
      cytokine concentrations. Significant post-inoculation elevations of interleukin
      (IL)-1beta, IL-6, and IL-10 were noted in untreated controls over 24 h.
      Telithromycin attenuated these increases and the suppression of both IL-6 and IL
      10 release was observed to be dose dependent. Systemic concentrations of IL-2 and
      tumor necrosis factor alpha showed an upward trend over the initial 8-h post
      inoculation period in the telithromycin group. These data therefore reveal novel
      in vivo immunomodulatory effects of telithromycin. Further studies are warranted
      to determine whether such effects contribute to the therapeutic efficacy of the
      drug in patients with acute respiratory tract infections.

PMID- 16649553
TI  - Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy
      induced by norepinephrine in rats.
AB  - Crocetin, a carotenoid isolated from the Chinese herbal medicine Crocus sativus
      L. (Saffron), has been shown to have cardiovascular protective effects. The
      present study investigated the protective action of the antioxidant crocetin
      against cardiac hypertrophy induced by norepinephrine (NE). This was evaluated by
      assaying for pathological histological changes with an optical microscope and
      cell image analysis system. Lipid peroxidation was quantified using
      thiobarbituric acid-reactive substances (TBARS). Myocardial superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px) and myocardial catalase (CAT) activities
      were assayed to evaluate the antioxidant capacity. After long term treatment with
      NE, antioxidant enzymatic activities were significantly decreased, while products
      of lipid peroxidation increased. Crocetin markedly reduced the content of lipid
      peroxidation (LPO), increased the GSH-Px and SOD activity in cardiac hypertrophy,
      and significantly improved the myocardial pathological histological changes
      induced by NE. These results suggest that the cardioprotective effects of
      crocetin are related to modulation of endogenous antioxidant enzymatic
      activities. Comparing crocetin with captopril, our results indicated that
      antioxidant activity is an important factor in the therapy of cardiac
      hypertrophy, but as an antioxidant only, its effects may be limited.

PMID- 16649554
TI  - Effect of Helicteres isora bark extract on blood glucose and hepatic enzymes in
      experimental diabetes.
AB  - The effect of oral administration of an aqueous extract of the bark of Helicteres
      isora was investigated on blood glucose and plasma antioxidant status in
      streptozotocin (STZ) induced diabetic rats. The study was also undertaken to
      evaluate the role of hepatic enzymes in experimental diabetes. Oral
      administration of a bark extract of Helicteres isora (100, 200 mg/kg) in STZ
      diabetic rats caused a significant increase in body weight, hepatic hexokinase
      activity and significant decrease in hepatic glucose-6-phosphatase, serum acid
      phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH).
      Based on these findings, we suggest that Helicteres isora possesses hypoglycemic
      and hepatoprotective activity and is able to ameliorate biochemical damage in STZ
      induced diabetic rats.

PMID- 16649555
TI  - Screening of new chemopreventive compounds from Digitalis purpurea.
AB  - Chemopreventive agents induce a battery of genes whose protein products can
      protect cells from chemical-induced carcinogenesis. In this study, we isolated
      four different glycosides (1 acteoside; 2 purpureaside A; 3 calceolarioside B;
      and 4, plantainoside D) from the leaves of Digitalis purpurea and studied their
      abilities to induce glutathione S-transferase (GST) and their protective
      efficiencies against aflatoxin B1-induced cytotoxicity in H4IIE cells. Of these
      four glycosides, acteoside significantly inhibited the cytotoxicity induced by
      aflatoxin B1 (AFB1) and also selectively increased GSTalpha protein levels.
      Reporter gene analysis using an antioxidant response element (ARE) containing
      construct and subcellular fractionation assays, revealed that GSTalpha induction
      by acteoside might be associated with Nrf2/ARE activation. The results suggest
      that acteoside possesses a potent hepatoprotective effect against AFB1 and that
      it can be applied as a potential chemopreventive agent.

PMID- 16649556
TI  - Screening of selected Arabian medicinal plant extracts for inhibitory activity
      against peptidases.
AB  - The methanolic extracts of 20 medicinal plants from the island Soqotra/Yemen were
      screened with respect to their inhibitory potency against angiotensin converting
      enzyme (ACE), neutral endopeptidase (NEP) and aminopeptidase N (APN). Eight
      extracts did not show significant inhibitory activity against the enzymes tested,
      only Kalanchoe farinacea, Boswellia elongata and Cissus hamaderohensis inhibited
      all three enzymes. The most active extract was prepared from Kalanchoe farinacea
      characterized by low IC50 values especially for NEP and APN.

PMID- 16649557
TI  - Assessment of neuropharmacological activities of Pandanus foetidus (Pandanaceae)
      in mice.
AB  - The methanol extract of the leaves of Pandanus foetidus Roxb. (Pandanaceae) was
      assessed for neuropharmacological activities in mice using a number of
      experimental models. The extract dose-dependently inhibited acetic acid-induced
      writhing in mice when given at the doses of 250 and 500 mg/kg body weight. At the
      same dose levels, it significantly prolonged the pentobarbitone-induced sleeping
      time in mice, and showed mild to moderate central nervous system depressant
      activity when assessed by the hole cross and the open field tests in mice model.
      On the basis of these findings, it can be assumed that the extract exerts its
      depressant effect on the central nervous system in mice by interfering with the
      cortical function.

PMID- 16649558
TI  - Two new 18-en-oleane derivatives from marine mangrove plant, Barringtonia
      racemosa.
AB  - Two new triterpenoids, olean-18-en-3beta-O-E-coumaroyl ester (1) and olean-18-en
      3beta-O-Z-coumaroyl ester (2), were isolated from the stem bark of marine
      mangrove plant Barringtonia racemosa, along with five known compounds,
      germanicol, germanicone, betulinic acid, lupeol, and taraxerol. Their structures
      were determined mainly by spectroscopic methods.

PMID- 16649559
TI  - Pluronic F127 gel effectively controls the burst release of drug from PLGA
      microspheres.
AB  - To investigate the controlled release effect of a thermo-sensitive gel, Pluronic
      F127 (PF127) on microspheres, poly[D,L-lactic-co-glycolic acid] (PLGA)
      microspheres were coated with Pluronic F127 gel and the in vitro release was
      evaluated. The results demonstrated that PF127, which gelled at 37 degrees C,
      inhibited the initial burst release of drug from microspheres effectively.

PMID- 16649560
TI  - Benazepril hydrochloride: effects of particle size on tablet properties.
AB  - Tablets manufactured from fine powder (average particle size, D[4,3] = 50.1
      microm) benazepril hydrochloride exhibited unacceptable processing and quality
      properties whereas microcrystalline material (D[4,3] = 4.5-7.7 microm) furnished
      a product with good processing and quality characteristics.

PMID- 16649561
TI  - Fault classification on vibration data with wavelet based feature selection
      scheme.
AB  - Fault classification based upon vibration measurements is an essential building
      block of a conditional based health usage monitoring system. Multiple sensors are
      incorporated to assure the redundancy and to achieve the desired reliability and
      accuracy. The shortcoming of using multiple sensors is the need to deal with a
      high dimensional feature set, a computationally expensive task in classification.
      It is vital to reduce the feature dimension via an effective feature extraction
      and feature selection algorithm. A simple wavelet based feature selection scheme
      is proposed herein, uniquely built by local discriminant bases and genetic
      optimization. This scheme overcomes the disadvantages faced by the existing
      feature selection methods by producing a generic feature set, reducing the
      dimensionality of features, and requiring no prior information of the problem
      domain. The proposed feature selection scheme is based upon the strategy of
      "divide and conquer" that significantly reduce the computation time without
      compromising the classification performance. The simulation results show the
      proposed feature selection scheme provides at least 65% reduction of the total
      number of features at no cost of the classification accuracy.

PMID- 16649562
TI  - An online novel adaptive filter for denoising time series measurements.
AB  - A nonstationary form of the Wiener filter based on a principal components
      analysis is described for filtering time series data possibly derived from noisy
      instrumentation. The theory of the filter is developed, implementation details
      are presented and two examples are given. The filter operates online,
      approximating the maximum a posteriori optimal Bayes reconstruction of a signal
      with arbitrarily distributed and non stationary statistics.

PMID- 16649563
TI  - Modeling, identification, and validation of models for predictive ammonia control
      in a wastewater treatment plant--a case study.
AB  - The aim of this work is to develop the ammonia models that could be used for
      model predictive control (MPC) of nitrification process in a wastewater treatment
      plant. First, a reduced nonlinear model is presented, which is based on
      expression for nitrification reaction rate in activated sludge model No. 1 and
      modified for attached biomass processes, while second, a linear black-box model
      is shown. The data used for model identification were collected during several
      weeks of experiments on a real plant so that good identification data were
      obtained. The designed models were validated based on open loop simulations and
      predictions. Validation results show that the reduced nonlinear model performs
      better compared to the linear model, however, both models show relatively large
      errors compared to the real plant data. Hence, a closed loop simulation study was
      performed to see the differences between the performance of model predictive
      controller using previously estimated linear and nonlinear models and a standard
      proportional integral (PI) controller. From the simulation study results it was
      seen that in spite of relatively large model errors the MPC algorithms give
      better results in terms of ammonia removal compared to the PI controller, while
      MPC with the nonlinear model shows additional improvements over the MPC with the
      linear model.

PMID- 16649564
TI  - Adaptive predictive functional control of a class of nonlinear systems.
AB  - This paper describes the use of pseudo-partial derivative (PPD) to dynamically
      linearize a nonlinear system, and aggregation is applied to the predicted PPD,
      resulting in a model-free adaptive predictive control algorithm for a nonlinear
      system. The algorithm design is only based on the PPD derived online from the
      input/output data of the controlled process, however it does provide bounded
      input/output sequence and setpoint tracking without steady-state error. A
      detailed discussion on parameter selection is also provided. To show the
      capability of the algorithm, simulations of a time-delay plant and a pH
      neutralization process show that the proposed method is effective for system
      parameter perturbation and external disturbance rejection.

PMID- 16649565
TI  - Limitations of a PI controller for a first-order nonlinear process with dead
      time.
AB  - A nonlinear process, the conical tank level process whose parameters vary with
      respect to the process variable, is considered. The time constant and gain of the
      chosen process vary as a function of level. A deliberate dead time is introduced
      in the system by delaying the valve opening. The limitations of the conventional
      PI controller tuned using Ziegler-Nichols settings for the chosen process are
      brought out. The servo and regulatory responses through simulation and
      experimentation for various magnitudes of set-point changes and load changes at
      various operating points with the controller tuned only at a chosen nominal
      operating point are obtained and analyzed. Regulatory responses for output load
      changes are studied. A benchmark system is presented to understand clearly how
      variations of system parameters affect the performance of the controller. A gain
      scheduled controller is proposed to handle the control problem. Present work
      illustrates the simplicity and effectiveness of the gain scheduling.

PMID- 16649566
TI  - Stochastic dynamic output feedback stabilization of uncertain stochastic state
      delayed systems.
AB  - This paper addresses the problem of stochastic dynamic output feedback (SDOF)
      stabilization for a class of stochastic continuous-time state-delayed systems
      with norm-bounded nonlinear uncertainties. The aim is to design a linear,
      delayless, and SDOF control for all admissible uncertainties. The designed
      control ensures stochastically exponentially stability in the mean square,
      independent of the deterministic time delay. Using the Finsler's lemma, the
      necessary and sufficient conditions for the existence of such a control are
      proposed in terms of certain linear matrix inequalities. These results are
      illustrated with a simple example to demonstrate the applicability of the
      proposed design approach.

PMID- 16649567
TI  - Large gap control in electromagnetic levitation.
AB  - This paper describes design and implementation of a single axis dc attraction
      type electromagnetic suspension system where an electromagnet of 2.6 kg mass is
      levitated over a large gap under a fixed ferromagnetic guide-way. The
      electromagnet exhibits nonlinear force-current-distance characteristics, and if
      controllers are to be designed by using linear analysis, the air-gap is
      restricted to a small region around the chosen nominal operating point. In this
      work, an attempt has been made to increase the operating range of an
      electromagnetic suspension system by using the concept of piecewise linear
      control where the nonlinear force-current-airgap relationships of the magnetic
      suspension system have been successively linearized at several operating points
      with a suitable controller designed for each operating point. A novel analog
      switching scheme has been designed and implemented to automatically switch to the
      relevant controller depending on the actual air-gap.

PMID- 16649568
TI  - Intelligent adaptive nonlinear flight control for a high performance aircraft
      with neural networks.
AB  - This paper describes the development of a neural network (NN) based adaptive
      flight control system for a high performance aircraft. The main contribution of
      this work is that the proposed control system is able to compensate the system
      uncertainties, adapt to the changes in flight conditions, and accommodate the
      system failures. The underlying study can be considered in two phases. The
      objective of the first phase is to model the dynamic behavior of a nonlinear F-16
      model using NNs. Therefore a NN-based adaptive identification model is developed
      for three angular rates of the aircraft. An on-line training procedure is
      developed to adapt the changes in the system dynamics and improve the
      identification accuracy. In this procedure, a first-in first-out stack is used to
      store a certain history of the input-output data. The training is performed over
      the whole data in the stack at every stage. To speed up the convergence rate and
      enhance the accuracy for achieving the on-line learning, the Levenberg-Marquardt
      optimization method with a trust region approach is adapted to train the NNs. The
      objective of the second phase is to develop intelligent flight controllers. A NN
      based adaptive PID control scheme that is composed of an emulator NN, an
      estimator NN, and a discrete time PID controller is developed. The emulator NN is
      used to calculate the system Jacobian required to train the estimator NN. The
      estimator NN, which is trained on-line by propagating the output error through
      the emulator, is used to adjust the PID gains. The NN-based adaptive PID control
      system is applied to control three angular rates of the nonlinear F-16 model. The
      body-axis pitch, roll, and yaw rates are fed back via the PID controllers to the
      elevator, aileron, and rudder actuators, respectively. The resulting control
      system has learning, adaptation, and fault-tolerant abilities. It avoids the
      storage and interpolation requirements for the too many controller parameters of
      a typical flight control system. Performance of the control system is
      successfully tested by performing several six-degrees-of-freedom nonlinear
      simulations.

PMID- 16649569
TI  - Computer control of a powered two degree freedom reciprocating gait orthosis.
AB  - The design of a motion control system for a powered reciprocating gait orthosis
      is considered. Models for the orthosis are obtained using least squares
      identification. The control system design is based on pole-placement techniques
      and a restricted Youla parametrization of the controller. Experimental results
      are included.

PMID- 16649570
TI  - Some practical aspects of designing a laboratory scale batch polymerization
      reactor without gas entrapment and interfaced with virtual instrumentation.
AB  - A 1-1 stainless steel (SS) reactor with a glass bottom has been designed with
      symmetrically placed internals so that gas entrapment is completely avoided
      during bulk polymerization of methyl methacrylate (MMA). This reactor is
      instrumented and controlled using virtual instrumentation. The power consumed by
      a constant-speed stirrer motor is measured as a function of time which, along
      with the temperature history, can be used to infer the state (monomer conversion
      xm and weight average molecular weight Mw) of the viscous reaction mass. This
      study highlights the importance of symmetry in the design of the reactor,
      proposes a novel reactor design, and discusses in detail the temperature control
      configuration that can help track any temperature history. Some preliminary
      results are reported for bulk polymerization of MMA and a correlation developed
      for the stirrer power, which can be used for soft sensing.

PMID- 16649571
TI  - Considerations for multivariable control of the twin-roller strip caster.
AB  - Twin-roller steel strip casters may offer advantages with respect to classical
      continuous casting hot rolling processes. Some works have reported control
      aspects of this process, however, the cross coupling elements have not been
      evaluated. In this work, the derivation of a 3 x 3 linearized multivariable model
      for process control purposes proposed in previous investigations is presented.
      The model was simplified to a 2 x 2 plant. The purpose of this work is to show
      that the process is highly interactive by performing an analysis of its
      multivariable characteristics. Some important considerations for process control
      design based on such multivariable characteristics of the process are discussed.

PMID- 16649572
TI  - Analysis of the use of industrial control systems in simulators: state of the art
      and basic guidelines.
AB  - The use of industrial control systems in simulators facilitates the execution of
      engineering activities related with the installation and the optimization of the
      control systems in real plants. "Industrial control system" intends to be a valid
      term that would represent all the control systems which can be installed in an
      industrial plant, ranging from complex distributed control systems and SCADA
      packages to small single control devices. This paper summarizes the current
      alternatives for the development of simulators of industrial plants and presents
      an analysis of the process of integrating an industrial control system into a
      simulator, with the aim of helping in the installation of real control systems in
      simulators.

PMID- 16649573
TI  - Investigations on the effect of the ruminal N-balance on rumen metabolism, urea
      content in blood serum and milk as well as some liver parameters of lactating
      cows.
AB  - Seven dairy cows fitted with ruminal and duodenal cannulae were used to
      investigate the influence of the amount of ruminally available N (Ruminal N
      Balance, RNB) on the rumen metabolism and to answer the question on the lowest N
      amount in the rumen, without negative effects on the fermentation. Animals were
      fed a ration on the basis of 7.9 kg corn silage and 7.2 kg concentrates related
      to dry matter, intended to meet the animals mean NEL and protein requirements.
      RNB amounted to -0.6 g/MJ ME in the basis ration. The other 3 rations were
      adjusted to RNB-values of -0.3, 0 and + 0.3 g/MJ ME by urea supplements in the
      concentrates. The increase in RNB resulted in higher NH3-N concentrations in the
      rumen fluid and in the duodenal digesta and higher urea concentrations in the
      blood and milk. The significantly highest amount of protein at the duodenum was
      detected when RNB showed an equilibrium (RNB = 0). The efficiency of microbial
      protein (MP) synthesis (gMP/kg fermented organic matter) was the same, g MP/d and
      g MP/MJ ME were significantly lower with RNB = -0.6g/MJ ME as compared to RNB =
      0. The group with thelowest RNB showed the highest level of feedprotein
      degradation as well as the lowest organic matter, NDF and ADF fermentation. An
      effect on cholesterol, total bilirubin and gammaGT due to different RNB was not
      detected. The activities of GLDH and AST were highest when the RNB was -0.6 g/MJ
      ME. From the results, it can be concluded that significantly negative effects on
      rumen fermentation occur when RNB-values are below -0.3 g/MJ ME. However, a
      positive RNB did not increase t he degradation and synthesis capacity of the
      rumen micro-organisms as compared to RNB = 0.

PMID- 16649574
TI  - Body composition, muscle fibre characteristics and postnatal growth capacity of
      pigs born from sows supplemented with L-carnitine.
AB  - Recently, it has been shown that supplementation of sows with L-carnitine
      increases their plasma concentrations of insulin-like growth factor (IGF)-I, and
      it has been hypothesized that this may stimulate fetal myogenesis. This study was
      performed to investigate whether piglets of sows supplemented with L-carnitine
      differ in muscle fibre characteristics, chemical body composition and postnatal
      growth capability from pigs of control sows. Muscle fibre characteristics and
      chemical body composition were determined at weaning in 21 piglets of control
      sows and 21 piglets of sows treated with L-carnitine with similar body weights;
      postnatal growth capability was determined from weaning until slaughter at a body
      weight of 118 kg in 80 pigs of control sows and 80 pigs of sows treated with L
      camitine which had also similar body weights at weaning. Piglets of sows
      supplemented with L-carnitine did not differ in number, area, diameter and type
      (percentages of slow twitch oxidative + fast twitch oxidative fibres, and fast
      twitch glycolytic fibres) of muscle fibres in m. longissimus dorsi and m.
      semitendinosus and in chermical body composition (concentrations of dry matter,
      crude protein, crude fat) from piglets of control sows. Postnatal growth
      capability (body weight gains, feed conversion ratio) from weaning to slaughter
      as well as carcass composition (carcass yield, meat thickness, fat thickness) was
      also not different between pigs of sows treated with L-carnitine and pigs of
      control sows. In conclusion, data of this study do not support the hypothesis
      that L-carnitine supplementation of sows during pregnancy enhances fetal muscle
      fibre development and increases postnatal growth capability of the offspring.

PMID- 16649575
TI  - Dietary deficiencies of single amino acids: whole-body amino acid composition of
      adult rats.
AB  - To ascertain whether chronic amino acid deficiency alters the amino acid
      composition of the body, 44 adult female rats were randomly allocated to one of
      11 treatments which included one control group, ingesting an adequate diet with
      balanced protein, and ten deficient groups in which one group received protein
      deficient diets and the other groups consumed diets each deficient in a single
      essential amino acid. The degree of deficiency was adjusted to achieve a gradual
      decline in body weight to 85% of the initial weight and was then adjusted so that
      this weight was maintained until the end of the experiment at 93 days, when the
      rats were killed. Deficient rats had lower absolute weights of liver,
      gastrointestinal tract and muscle than animals given the adequate diet but
      greater relative weights (% of body weight) of heart and kidneys. There were no
      significant differences amongst groups in percentages of lipid, nitrogen, protein
      plus lipid or dry matter. Chronic marginal amino acid deficiencies did not
      selectively alter amino acid composition.

PMID- 16649576
TI  - Effect of microbial phytase on apparent ileal amino acid digestibility of
      phosphorus-adequate diets in growing pigs.
AB  - Six ileally cannulated pigs (mean initial body weight 34.8 kg) were used to study
      the effect of microbial phytase on apparent ileal digestibility of P, total N and
      amino acids. Three P-adequate diets (digestible P concentration 2.3 g kg(- )l)
      containing barley (B), soyabean meal (S) or a mixture of the two (BS) with or
      without phytase supplement (1000 FTU x kg(-1)) were fed to pigs using a 6 x 6
      Latin square design. The addition of phytase increased (p < 0.05) apparent ileal
      P digestibility of diets B, S and BS by 16.5, 19.2 and 19.2%, respectively. There
      was no effect of phytase on the ileal digestibility of total N. Apparent ileal
      digestibility of amino acids tended to increase in the BS diet supplemented with
      phytase (mean improvement of 2.2%); but no significant difference was found for
      any amino acid as compared with the unsupplemented diet. To asses the additivity
      of apparent amino acid digestibility, the determined values for the BS diet were
      compared to those calculated from digestibilities found in diets B and S. There
      were no significant differences between the determined and calculated values. It
      is concluded that the addition of microbial phytase to P-adequate diets does not
      affect ileal amino acid digestibility in growing pigs and that the apparent amino
      acid digestibility values determined in single ingredients may be additive when
      included into a complex diet.

PMID- 16649577
TI  - Influence of a Fusarium culmorum inoculation of wheat on the progression of
      mycotoxin accumulation, ingredient concentrations and ruminal in sacco dry matter
      degradation of wheat residues.
AB  - The Fusarium head blight (FHB)-susceptible winter wheat cv. Ritmo was inoculated
      with spores of Fusarium culmorum at the beginning of full blossom. Samples of
      whole wheat plants were taken once weekly from anthesis until harvest and
      subsequently fractionated into straw, glumes and spindles, which were examined
      for deoxynivalenol (DON) and zearalenone (ZON). Additionally, the content of
      crude protein (CP) and non-starch polysaccharides (NSP) was scrutinized.
      Synthesis of the Fusarium toxins DON and ZON generally differed in terms of date
      of formation and concentration. Final mean DON concentrations of 37.5, 28.1 and
      5.0 mg/kg DM were measured in glumes, spindles and straw, respectively, at the
      time of harvest. At this time, maximal mean ZON concentrations of 587, 396 and
      275 microg/kg DM in spindles, glumes and straw, respectively, were determined.
      Moreover, Fusarium infected wheat residues contained higher CP but lower NSP
      contents at the last three sampling dates. In addition, collective samples of
      wheat straw and chaff were taken to investigate the effect of the Fusarium
      contamination on their in sacco DM degradation in dairy cows. Samples were
      analysed for mycotoxins and selected quality parameters. The dried and milled
      collective samples of straw and chaff were weighed into nylon bags and subjected
      to ruminal incubation for 4, 8, 16, 24, 48, 72, 96 and 120 h in two dairy cows
      equipped with a permanent rumen cannula. Marked differences in level of mycotoxin
      contamination as well as in ingredient composition between the variants of straw
      and chaff were detected. Moreover, after 120 h rumen incubation the in sacco DM
      degradation of inoculated straw and chaff were lower compared to the accordant
      controls. The soluble fraction was increased in inoculated samples, whereas a
      diminishment in the potentially degradable but insoluble fraction was more
      pronounced. Thereby, a decrease in the potential degradability was obtained for
      inoculated straw and even if less pronounced for chaff compared to the non
      inoculated corresponding controls. In conclusion, infection with F. culmorum of
      wheat involves an increased risk of mycotoxin contamination in straw. Also, a
      Fusarium infection may have an impact on chemical composition and may result in
      Fusarium growth-related modifications of host cell wall components.

PMID- 16649578
TI  - Fermentation of wheat: effects of backslopping different proportions of pre
      fermented wheat on the microbial and chemical composition.
AB  - The objective of the study was to examine effect of backslop on the chemical and
      microbiological characteristics of fermented wheat (FW). Coarsely ground wheat
      was mixed with water (1:3 wt/wt) and inoculated with 6 log cfu ml(-1) each of an
      overnight culture of Lactobacillus plantarum and Pediococcus pentosaceus. Four
      fermentation treatments were conducted in 45 1, closed, PVC containers over 48
      hours. Three treatments investigated the benefits of the addition of previously
      fermented wheat (backslopping, BSL) at different proportions (0.20, 0.33 or 0.42
      kg) to freshly prepared wheat. The control treatment contained no addition of
      BSL. Elimination of coliforms from the FW within 48 h was only achieved through
      backslopping; where coliform bacteria counts decreased from approximately 6.5
      log10 cfu ml(-1) to less than 3 log10 cfu ml(-1). There was no apparent advantage
      in increasing the backslop proportion above 0.20. However, the exclusion of
      coliform bacteria required the pH to remain below 4.0 for at a minimum of 24 h.
      The results of these studies indicate that fermentation of wheat has the
      potential to reduce the risk of feed-borne colibacillosis and provides a
      practical alternative to producers that cannot ferment multiple diets or have
      limited fermentation capacity.

PMID- 16649579
TI  - Effects of extrusion of corn on growth performance, nutrient digestibility and
      short-chain fatty acid profiles in the hindgut of weaned piglets.
AB  - The experiment was conducted to investigate the effects of different inclusion
      levels of extruded corn on growth performance, nutrient digestibility and short
      chain fatty acids profiles in the hindgut of weaned piglets. Ninety weaning
      piglets (28 d of age; 8.21 +/- 0.69 kg BW) were allotted to one of five dietary
      treatments only substituted for unprocessed corn at varying levels (0, 1/4, 2/4,
      3/4, 4/4) with extruded corn in a 28-d experiment. On day 28, 30 piglets were
      killed to measure concentrations and molar ratios of short-chain fatty acids in
      the hindgut. From day 0-14, digestibility of DM, N and GE was increased linearly
      and diarrhea frequency was decreased due to the increasing inclusion levels of
      extruded corn. From day 14-28, digestibility of GE and N was enhanced linearly
      due to the increasing proportion of extruded corn. On day 28, as proportion of
      extruded corn increased, the level of butyrate in the caecum and colon was
      increased linearly and the relative proportion of propionate was reduced. Results
      indicated that increasing proportions of extruded corn had no effect on growth
      performance, but significantly improved digestibility of N and energy at day 10
      of trial and may be advantageous to the intestinal health of piglets.

PMID- 16649580
TI  - In vitro degradation of the flavonol quercetin and of quercetin glycosides in the
      porcine hindgut.
AB  - The present study investigated the microbial degradation of the plant flavonol
      quercetin and its naturally occurring glycosides isoquercitrin and rutin in the
      porcine hindgut. The experiments were carried out with the semicontinuous colon
      simulation technique. The fluid and particle phase of pig hindgut contents from
      freshly slaughtered animals were used for the in vitro incubations. Following a
      five-day equilibration period, quercetin, isoquercitrin or rutin were
      administered to fermentation vessels and their turnover rate was determined. None
      of the flavonols affected parameters of microbial fermentation like pH, redox
      potential or VFA production. The turnover rate for isoquercitrin was seven times
      higher than the turnover for the fermentation fluid. The turnover rates for
      quercetin and rutin were four and twofold higher than fluid turnover,
      respectively. After administration of isoquercitrin or rutin, their aglycone
      quercetin was detected as an intermediary metabolite. Under sterile conditions
      using autoclaved incubation fluids and hindgut contents, turnover rates for
      quercetin and rutin were still higher than the fluid turnover in the fermentation
      vessels. This indicates a certain chemical instability of the flavonols and/or
      adsorption to ingesta particles. Thus, flavonols are subjected to microbial
      metabolism in the porcine hindgut. The glycosidic structure strongly influences
      the rate of metabolism.

PMID- 16649581
TI  - [Benign hypertrophy of the prostate (BHP) in France: a challenge in organization
      of care].

PMID- 16649582
TI  - [Histologic forms of benign prostatic hyperplasia: focus on fibroblastic
      factors].

PMID- 16649583
TI  - [Benign prostatic hyperplasia (BPH) and metabolic syndrome: a single
      comorbidity].

PMID- 16649584
TI  - [Evaluation of urination disorders in the male: is there a place for a diuresis
      calendar?].

PMID- 16649585
TI  - [The objective of medical treatment: relieve the symptoms or stop the course?].

PMID- 16649586
TI  - Leaching of As(III) and As(V) from exhausted calsico--a case study.
AB  - Batch leaching experiments were conducted to estimate the leaching of As(III) and
      As(V) from exhausted CalSiCo. The leaching of As(III) and As(V) was found to be
      function of time and concentrations of anions such as Cl-, NO3-, SO4(2-) in
      extraction fluid. Extraction tests were carried out to determine the maximum
      leachable concentration under the chosen conditions of leaching medium and
      leaching time. It has been observed that the leaching of As(III) is more than
      As(v) in all the cases. Leaching of As(III) and As(v) from exhausted CalSiCo is
      also carried out in rainwater and in tap water. It is observed that leaching of
      As is more in rainwater than tap water. Further higher leaching is observed in
      case of fluids containing chloride compared to those containing nitrate and
      sulphate.

PMID- 16649587
TI  - Composting of partially decomposed agroresidues.
AB  - Biphasic biodegradation of any organic waste has several advantages over
      conventional anaerobic digestion but has a problem of generation of a large
      quantity of partially decomposed residues in the acid reactor of the system that
      require further processing to make them safe for disposal. Composting of these
      residues was attempted and the quality of final product was analysed. A
      stabilized and very good quality compost was produced. The details of the
      experiments and results are discussed in the paper.

PMID- 16649588
TI  - Benzene, toluene and xylene (BTX) pollution in ambient air: a case study.
AB  - Volatile Organic Compounds (VOCs) in presence of sunlight and oxides of nitrogen
      in atmosphere are considered as precursors for ozone production at the ground
      level. Concentration of Benzene, Toluene and Xylene (BTX) in ambient air was
      measured near seven traffic junctions in the city of Nagpur. Air samples were
      collected using Organic Vapour Sampler and analyzed by Gas Chromatograph equipped
      with Flame Ionization Detector (FID). Benzene concentration was found to be in
      the range 9.3 to 28.7 microg/m3, Toluene 3.26 to 21.0 microg/m3 and Xylene 4.9 to
      15.0 microg/m3. These values are lower than those found in Metropolitan cities
      like Mumbai.

PMID- 16649589
TI  - Assessment of air pollution indices in opencast coal mining complex--an Indian
      case study.
AB  - India is world's third largest coal-producing country and to meet the future
      energy demand it will have to produce coal at a faster rate. The coal by opencast
      mining has been about 80% of the total production. This paper focuses on some of
      the key air pollution problems arising from increased use of opencast mining. It
      examines the utility of an Air Pollution Index (API) for tackling air pollution
      problems. A fact-finding survey was conducted to evaluate the status of air
      pollution due to opencast coal mining in Jharia Coalfield of Bharat Coking Coal
      Ltd. The approach for the selection of air monitoring stations, its monitoring
      programme, data analysis and results are discussed. The Oak Ridge Air Quality
      Index (ORAQI) was used to evaluate the relative ranking of overall air quality
      different locations within the mining complex. The paper recommends the use of
      API data rather than individual air pollution level data when attempting to
      develop effective air pollution control strategies for mining areas.

PMID- 16649590
TI  - Assessment of the impacts of vehicular pollution on urban air quality.
AB  - Air quality crisis in cities is mainly due to vehicular emissions. Owing to the
      expanding economic base Indian cities are growing at a faster rate.
      Transportation systems are increasing everywhere and the improved technology is
      insufficient to counteract growth. The effect of vehicular emission on urban air
      quality and human health has been described. A survey has been conducted in an
      Indian mega city to evaluate the status of air pollution at traffic intersections
      and the unique problem arising out of vehicular emissions in the study area has
      been narrated. Approach for the selection of the air monitoring stations,
      methodology adopted for data collection and the results have been discussed.
      Vulnerability analysis (VA) has been carried out to identify the zones at what
      pollution stress. Options for reducing mobile source emission have been discussed
      and a strategic air quality management plan has been proposed to mitigate the air
      pollution in the city.

PMID- 16649591
TI  - Development of an evaluation criteria for rural water supply and environmental
      sanitation programme in project and non-project villages--a case study.
AB  - The Rural Water Supply and Sanitation (RWSS) in project and non-project villages
      of Mysore Taluk has been evaluated and discussed in this paper. The study area
      covered two villages (Yelwala and Kadakola) where Integrated Water Supply Scheme
      (IRWSS) was implemented under World Bank Project and two non-project villages
      (Belwadi and Byathahalli) closer to them. Pre and post scenarios of the project
      and non-project villages were investigated in terms of water quality analysis and
      also grading of villages has been done on the basis of water supply, sanitation,
      hygienic awareness and practices. Matrix methodology was used to evaluate the
      indicators from the survey data gathered from all studied villages. Finally, the
      villages were graded on the basis of cumulative value obtained for each village.
      Water quality analysis depicted turbidity, total dissolved solids and hardness
      being high and iron deficiency was also observed in water samples of all the
      villages. It was concluded that the present method of evaluation of rural water
      supply and sanitation project could be effectively applied to different upcoming
      projects.

PMID- 16649592
TI  - Effect of noise on human performance under variable load in a die casting
      industry--a case study.
AB  - The manual mode of working in industries is very common in the developing and
      under developed countries. Many industrial processes have generated high levels
      of noise and causing physiological effects on operators and thus leading to
      reduced performance. A survey was carried in various die casting industries to
      determine the levels of noise. It was found that the levels were in the range of
      80-100dB(A). The survey also showed that the effects were more pronounced when
      the task was conducted under varying load conditions. Keeping this in view the
      problem was formulated to study whether the level of noise and amount of load has
      a bearing on human performance. For this purpose, experimental investigations in
      a simulated environment were carried out. Five subjects, all males and having no
      experience in the trade were selected for the task. The levels of noise under
      taken were 80, 90 and 100 dB(A) while the levels of load were 150, 200 and 250 N.
      A pulse oximeter was used to measure the human performance in terms of heart
      rate. The data was collected and analyzed on the basis of two factor repeated
      measure type of experimental design. Results of the study indicated that the
      level of noise and load both were having statistically significant effect on
      human performance. However, the interaction of level of noise and load was found
      to be statistically non-significant. The findings of the present work have been
      discussed in the light of the previous researches carried out on the topic.
      Suggestions have been made to reduce the levels of noise as per the
      recommendations of Occupational Safety and Health Association (1990). It is also
      suggested that instead of hand operated machines, foot operated versions should
      be used to reduce fatigue.

PMID- 16649593
TI  - Bio-medical waste management in the U.T., Chandigarh.
AB  - Investigations were carried out to assess the generation and disposal of
      biomedical waste in the various medical establishments in the urban and rural
      areas of the U.T. Chandigarh. It was found that there were 474 medical
      establishments in the U.T., Chandigarh including Nursing Homes, Clinics,
      Dispensaries, Pathological labs., Hospitals, Veterinary Institutions and Animal
      houses. The total quantity of bio-medical waste generated in Chandigarh is 811.35
      kg/day and the rate of generation of bio-medical waste varies from 0.06
      kg/day/bed to 0.25 kg/day/bed. Though the major hospitals are equipped with
      incinerators, proper bio-medical waste management system is yet to be
      implemented. The medical establishments in the rural area and smaller ones in the
      urban area dispose off their bio-medical waste along with municipal solid waste
      and no waste management system exists. It is recommended that an integrated waste
      management plan using the three incinerators installed at the major hospitals can
      safely dispose off the total bio-medical waste generated in the city.

PMID- 16649594
TI  - Ground water contamination in the area adjoining zinc smelter effluent stream.
AB  - A preliminary survey of the area adjoining to zinc smelter effluent stream was
      undertaken to assess ground water contamination. Twenty-five ground water samples
      from the wells located in the study area were collected and grouped into nine
      groups based on their lateral and longitudinal position from the stream carrying
      the effluent discharged from zinc smelter, Debari- Udaipur. The study indicate
      that waters of wells situated in the vicinity of effluent stream (255m radius)
      were of medium salinity having higher levels of Ca and Mg and lower values of pH
      as compared to the waters of the reference wells situated far away from the
      effluent stream. The Fe, Zn, Cd, Cl, F and SO4 contents ofthe water from the
      wells located within 80m vicinity of the effluent stream were above the
      permissible limits for drinking purposes. Furthermore the Zn, Cl and SO4 levels
      in these waters were so high that they were even not suitable for irrigation,
      indicating a gradual encroachment of effluent into the native ground water.

PMID- 16649595
TI  - Heavy metals accumulation in soils irrigated by municipal and industrial
      effluent.
AB  - Four soil profiles have been exposed in municipal, industrial effluents and
      municipal wastes mixed with industrial wastes (mixed effluent) and tube well
      irrigated areas of Indore district of Madhya Pradesh. Soil samples were collected
      horizon wise and analyzed for pH, electrical conductivity (EC), organic carbon,
      CaCO3, clay content, cation exchange capacity (CEC), exchangeable sodium
      percentage (ESP) and heavy metals content viz. Fe, Mn, Zn, Cu, Cd, Cr, Co and Pb.
      Results showed all the heavy metals content decreased with increase in depth of
      soil profile. Municipal wastes / untreated sewage affected soil of Bhangarh
      village depicted highest content of heavy metals. The order of percentage
      availability of different heavy metals irrespective of the sources of irrigation
      is Pb>Co>Cr>Cd. However, continuous application of sewage indicated higher
      accumulation of heavy metals although the rate of accumulation was faster in case
      of industrial effluent within 2 years of irrigation. Organic carbon content had
      significant positive correlation with heavy metals except Cu and Zn, and negative
      correlation with pH and CaCO3. ESP had a negative correlation with all the
      metals. Zn, Mn, Cd and Co indicated significant negative correlation with the CEC
      of the soil. Inter-metallic correlation indicates a significant positive
      correlation in between Fe, Cu, Zn, Mn, Co, and Pb and among themselves.

PMID- 16649596
TI  - Chemical analysis of ground water of Sanganer area, Jaipur in Rajasthan.
AB  - The chemical analysis of ground water quality of Sanganer area, Jaipur in
      Rajasthan is presented in this paper. It is important from this point of view to
      observe the suitability of water for safe drinking and irrigation. The different
      parameters measured are pH, conductivity, TDS, calcium, magnesium, total
      hardness, COD, alkalinity, Cl-, F-, PO4(3-), Na+, K+, SO4(2-), NO3-, Cd2+, Pb2+
      and Fe2+. From the observed data it is found that parameters like conductivity,
      TDS, alkalinity, F- have high values in this area whereas other parameters are
      approximately with in the limits or below limit.

PMID- 16649597
TI  - Genesis of domestic sewage--case study of a residential university campus.
AB  - The study reports on the genesis of domestic sewage in a predominantly
      residential university campus area ofDhanbad, Jharkhand. The domestic sewage has
      been collected from three different locations of the campus area and their
      physicochemical characteristics have been studied. These studies reveal that the
      extent of mineral pick-up is different for different parameter. It has been found
      out in the present study that in the domestic sewage, the chloride pick-up is
      71%, nitrate pick-up is 97%, total hardness pick-up is 20 %, iron pick-up is 98%
      and zinc pick-up is 98%. The rate constants have been found out by using standard
      methods and have been compared with those mentioned in the standard literatures
      and previous works.

PMID- 16649598
TI  - Air quality status at selected locations in Hyderabad City.
AB  - A case study for assessing the air quality status is elaborated for Hyderabad
      city. Monitoring was carried out at 11 locations during March 2003. These
      observations on air quality status and AQEI predicts that most of the localities
      in Hyderabad are experiencing the air pollution stress and the trend is likely to
      worsen in near future if proper control measures are not implemented.

PMID- 16649599
TI  - Urban air pollution forecasting with respect to SPM using time series neural
      networks modelling approach--a case study in Coimbatore City.
AB  - The Coimbatore city due to its climatic conditions and industrial development is
      experiencing an exponential growth in the vehicular usage and fuel consumption.
      On the other hand, the existing weather pattern of the city is not favourable for
      the dispersion of pollutants. This paper presents the evolution of SPM
      forecasting models for the prediction of SPM one week in advance. Time series
      neural networks approach is used for modelling. The input variables are the
      meteorological parameters, the concentration of SPM one week before and the
      concentration of SPM on the monitoring day. The evolved models of SPM for
      selected monitoring stations will be useful for the effective functioning of the
      air quality management programme.

PMID- 16649600
TI  - Characterization and management of municipal solid waste of Srinagar-Garhwal.
AB  - Characterization and physico-chemical composition of municipal solid waste of
      Srinagar-Garhwal, a hill town of Uttaranchal were carried out to know the
      composition of solid waste for its efficient management. A total of 28,56,500 kg
      (2,856.5 tonnes) of solid waste was produced per annum. A disposal site away from
      the open bank of Alaknanda has been suggested. 1,500 m3 volume of land will be
      required for the land filling of half of the solid waste generated in Srinagar
      town. In addition to it, 60 numbers of trenches (size 10 m x 3 m x 1 m) with
      clear spacing of 2.0 m will be required for the composting of remaining half of
      the solid waste. A list of suggestions has also been made for reducing the waste
      generation at source.

PMID- 16649601
TI  - Studies on persistence of temephos in sandy loam soil under field and laboratory
      conditions.
AB  - Persistence of temephos was studied in soils under field and laboratory
      conditions in sandy loam soil to evaluate the effect of moisture and formulations
      on persistence. The insecticide was applied as 50 EC and 1 % S.G. granules @1 kg
      a.i. ha-1 on surface of the soil' and residues were determined
      spectrophotometrically. The soil was fortified separately with dilute emulsion of
      EC and suspension of granular formulation at 5 ppm level and incubated at
      different moisture levels at 25:1:1 degrees C for 90 days. The residues of
      temephos from both the formulations persisted upto 55 days in soil when applied
      @1 kg a.i. ha(-1). In 40 days 92 and 91.43 per cent temephos was dissipated from
      soil treated with EC and granular formulations, respectively. There was no
      leaching or downward movement of the toxicant beyond 7.5 cm. The half-life of
      temephos under field condition for EC and granular formulations were 18.14 and
      20.44 days, respectively. Statistically, there was no significant effect of two
      formulations of temephos on its persistence. But at three different moisture
      conditions viz. airdry, field capacity and sub-merged, the difference was
      significant at 5% level.

PMID- 16649602
TI  - Anaerobic sustainability for integrated biomethanation of sugar mill waste and
      municipal sewage.
AB  - The study investigates the viability of biogas generation by integrating the
      biodegradable waste product of sugar industry viz., pressmud with municipal
      sewage using biomethanation process. The total solid content of pressmud and
      sewage mixture was optimized with respect to maximization of biogas yield with
      continuous monitoring over several operating parameters. Optimum total solid
      content of 5% found to yield 80 m3 of biogas per ton of pressmud compared to 65m3
      per ton of conventional digestion of pressmud alone. It is estimated that 3.4 x
      10(8) m3 of biogas can be generated through integrated biomethanation from the
      potential of4.2 million tons ofpressmud available annually in India.

PMID- 16649603
TI  - Batch kinetic modeling of arsenic removal from water by mixed oxide coated sand
      (mocs).
AB  - A new granular media developed by coating of iron and manganese on quartz sand
      surface proved to be effective for arsenic (III) removal from water. The media
      has shown alkali resistance. The kinetic and thermodynamic studies data were
      tested using pseudo-second- order, intraparticle diffusion and Elovich equation
      models. The rate constants, equilibrium sorption capacity and normalized standard
      deviations were calculated for all the three models. It was shown that all three
      models almost accurately predict the sorption capacity with respect to time for
      whole range of data points. However, sorption kinetic data were better correlated
      using Elovich equation model based on normalized standard deviation. The Langmuir
      and Freundlich isotherm equations could be used to describe the partitioning
      behavior of system at different pH and media size. The results of thermodynamic
      studies show that the As(III) adsorption on Mixed Oxide Coated Sand (MOCS) was
      endothermic in nature. Kinetic and isothermal studies data have also been used to
      obtain thermodynamic parameters of the process.

PMID- 16649604
TI  - Removal of toxic Cr(VI) by the adsorption of activated carbons prepared from
      Simarouba shells.
AB  - Removal of toxic Cr(VI) in aqueous medium was investigated using activated carbon
      adsorbents prepared from Simarouba glauca seed shells. The pH effect, Cr(VI)
      concentration, adsorbent dosage and contact time period were studied in batch
      experiment. The removal of Cr(VI) was in general most effective at pH range 2.0
      4.0 and high Cr(VI) concentrations. Activated carbons are prepared at 80050
      degrees C temperature. One is non-impregnated and the remaining three are
      impregnated with zinc chloride in 1:1,1:2,1:3 ratio. Important characteristics of
      activated carbons are also investigated. The data for all the adsorbents fit well
      to the Freundlich adsorption isotherm. The removal of Cr(VI) is around 97% was
      observed with 1:2 impregnated activated carbon at pH 3.0 where as other
      adsorbents showed much lower activities.

PMID- 16649605
TI  - Street-level concentrations of suspended particulate matter (SPM), nitrogen
      dioxide (NO2) and sulphur dioxide (SO2) in Pune City.
AB  - The concentration of suspended particulate matter (SPM), nitrogen dioxide (NO,)
      and sulphur dioxide (SO2) were measured at 13 important traffic intersections in
      Pune city. In order to study the contribution of these pollutants from motor
      vehicles, attention was focused on the roadside, street-level concentration. The
      statistical analysis of the sampling results indicates that there is not only
      high correlation between SPM and NO2 but the levels of these pollutants are above
      the National Ambient Air Quality Standards (NAAQS) laid down by the Central
      Pollution Control Board (CPCB), India. The SO, concentrations are found to be
      well below the NAAQS.

PMID- 16649606
TI  - Growth, nodulation and dry matter yield of blackgram cultivars under nickel
      stress.
AB  - Four cultivars of blackgram (Vigna mungo (L.) Hepper) were grown in soil amended
      with nickel (0, 50, 100, 150 and 200 mg/kg) and analysed on the 45th day. Nickel
      at all levels tested reduced the length of root and shoot, number of nodules,
      area of leaves and dry matter yield of root and shoot of blackgram cultivars. The
      reduction was lower in AB-1903 and ADT-3 than in ADT-4 and ADT-5. Cultivars AB
      1903 and ADT-3 were less sensitive than ADT-4 and ADT-5. The accumulation of
      nickel was higher in roots than in shoots. The increase of nickel content in
      roots of blackgram did not differ with cultivars. However, the accumulation of
      nickel in shoots of blackgram differed with cultivars. The sensitive cultivar ADT
      4 and ADT-5 accumulate more nickel in their shoots than the other cultivars, AB-
      1903 and ADT-3.

PMID- 16649607
TI  - Mass balance approach for assessment of pollution load in the Krishna River.
AB  - River Krishna in the Southern Peninsula of India is a typical receiving water
      body of both point and non-point discharges. Comparisons between upstream and
      downstream monitoring sites reveal changes in the concentrations and load to the
      river. This information is used to discriminate between point and non-point
      source contribution to pollution. The pre-monsoon and post-monsoon water quality
      and flow data are used to assess river pollution loads. The resulting
      differential loads, if adjusted for uncharacterized non-point source contribution
      may represent the total point loads to the river minus losses due to
      volatilization, sedimentation, adsorption and other physical, chemical and
      biological phenomena. The results of the mass balances indicate that non-point
      sources to be major contributors to the pollutant loads. The non-point sources in
      the study area predominantly include pollution due to agricultural practices and
      activities, soil erosion, dissolution of soil minerals or combination of these
      sources.

PMID- 16649608
TI  - Removal of azo dyes from aqueous solutions using activated carbon as an
      adsorbent.
AB  - The potentiality of commercially available activated carbon has been investigated
      as an effective adsorbent to remove the dyes from aqueous solutions. The effects
      of pH of the solution, adsorbent dose, solute concentration and temperature on
      activated carbon for azo dyes such as acid orange 7 and direct red 31 have been
      evaluated. The percentage removal of the dyes has been found to be high at
      neutral pH. The dynamics of adsorption has been studied at different
      temperatures. The adsorption data follow Langmuir model as well as Freundlich
      model in the case of acid orange 7 whereas the data for direct red 31 fit into
      only Langmuir model.

PMID- 16649609
TI  - Effect of vermicomposting process on metal content of paper mill solid waste.
AB  - In the present study the change in metal content on vermicomposting of paper mill
      solid waste was studied. On vermicomposting, quantity of iron, zinc and chromium
      found to be increased whereas quantity of aluminium, copper, manganese, nickel
      and lead found comparatively low. The bioaccumulation of any metal was not
      observed in the body of the earthworm, hence after vermicomposting, there is no
      harm to fishes to utilize earthworm biomass as their food. The metal content in
      the vermicompost prepared from the paper mill solid waste was well within the
      permissive limits and can therefore be safely applied in an aquaculture,
      agriculture and other food production systems.

PMID- 16649610
TI  - Uranium, radium and radon exhalation studies in geological samples belonging to
      some areas of punjab, using track etching technique.
AB  - With a view to prospect the uranium, radium and radon concentration and related
      health risk assessments in areas of Muktsar and Ferozepur districts in Punjab,
      the fission track registration technique has been used for the analysis of water
      and soil samples. Uranium content in water ranged from 5.47 to 10.19 microg/l(-1)
      and 6.28 to 11.74 microg/l(-1) for Muktsar and Ferozepur respectively. Uranium
      content in soil samples of Muktsar and Ferozepur ranged from 1.14 to 1.90 mg/kg(
      1) and 1.26 to 2.44 mg/kg(-1) respectively. Radium concentration in these soil
      samples has been found to vary from 3.97 to 15.94 bq/kg(-1) and 7.24 to 24.14
      bq/kg(-1) for Muktsar and Ferozepur respectively. The radon exhalation values
      were calculated in terms of area (E(A)) and mass (E(M)). The values of E(M)
      ranged from 4.9 to 20.6 (mbqkg(-1) hr(-1)) for Muktsar and 9.4 to 31.3 (mbqkg(
      1)hr(-1)) for Ferozepur and values of E(A) ranged from 173 to 728 (mbqm(-2)hr(
      1)) for Muktsar and 330 to 1102 (mbqm(-2)hr(-1)) for Ferozepur district. These
      values in general are low and not significant from health hazard point of view.
      The values of uranium concentration in water samples of these areas are lower
      than those reported for soil and water samples of Himachal Pradesh. These values
      are also lower than those reported by Singh et al. for the rocks belonging to
      uranium and copper mines of Bihar.

PMID- 16649611
TI  - Is environmental degradation the root cause for communicable diseases in kerala?
      A case study.
AB  - In Kerala (India), environmental degradation, consequent to urbanization,
      industrialization and skewed agricultural practices, is on the rise. The urban
      area has acute land and water pollution due to these activities. In
      Thiruvananthapuram district, especially in certain pockets of squalor and poor
      environmental quality, communicable diseases are being reported frequently. The
      present study aims to highlight the causes of environmental degradation which are
      directly related to the health issues of Thiruvananthapuram district. Based on
      this study some recommendations are also made for enhancing the environmental
      quality of the region.

PMID- 16649612
TI  - A study of effects of acid activated saw dust on the removal of different
      dissolved tannery dyes (acid dye) from aqueous solutions.
AB  - The effectiveness of acid activated sawdust in absorbing D-Brown EGP and Lurazol
      Brown PM dyes from aqueous solutions was studied as a function of agitation time
      and initial dye concentration. The experimental data were fitted to Langmuir and
      Freundlich isotherm and found that adsorption process follows both the isotherms.
      The values of Langmuir and Freundlich constants indicate favorable and beneficial
      adsorption. Saw dust is an excellent low cost adsorbent of colored organic anions
      and may have significant potential as a color removal from tannery wastewater.

PMID- 16649613
TI  - Treatment of metallic effluents using coconut shell coke.
AB  - The effect of various parameters on the removal of metal ions (Zinc and Cadmium)
      by adsorption using coconut shell coke is investigated. The time of contact,
      initial metal ion concentration, adsorbent dosage, volume of the adsorbate
      solution, size of the adsorbent particle and the effect of the presence of
      another metal at various concentrations are the parameters studied. The
      adsorption isotherms so obtained in this study followed the Freundlich and
      Langmuir isotherms showing a marginal average deviation.

PMID- 16649614
TI  - The effect of carbon as an energy source for biological denitrification through
      Pseudomonas stutzeri.
AB  - The biological denitrification processes possess many advantages in comparison to
      other denitrification processes. The present study was undertaken to observe the
      effect of quantity of carbon on biological denitrification with Pseudomonas
      stutzeri at different C/N ratios. The results obtained in the present
      investigations show that the pH and alkalinity of the effluent increased with
      increase in C/N ratio due to alkalinity generated during denitrification. The COD
      of the influent was increased with increase in C/N ratio. The effluent COD was
      nil under pseudo-steady state condition up to the C/N ratio of 2.5. Above this
      C/N ratio, the organics started entering in the treated water. The maximum
      feasible economic reduction of NO(3-)N from 51.6 mg/l to 1.2 mg/l occurred at C/N
      ratio of 2.5 and the obtained concentration of NO(3-)N was found to be lower than
      the tolerance limit (10 mg/l) prescribed by the WHO. The present work provides a
      feasible approach for a more efficient NO(3-)N removal process.

PMID- 16649615
TI  - Effect of an acute and chronic toxicity of four commercial detergents on the
      freshwater fish Gambusia affinis Baird & Gerard.
AB  - The toxic effects of four commercial detergents (two washing powders and two
      cakes) are reported in this paper on behavior, mortality and RBC counts of a
      freshwater fish Gambusia affinis. During acute toxicity studies (96h), surface
      movements of fish increased markedly for 24h, only at higher concentrations (>10
      ppm) of all the four detergents. Thereafter, they were lethargic and bottom
      dwellers similar to those exposed for a period of 30 days in the longterm
      ecotoxicological studies made on detergent powders at a sublethal concentration
      (10 ppm). The detergents exposed to fish were found slippery due to mucous
      secretion. Hemorrhage regions were also found on their gills. The dissolved
      oxygen content also decreased (10-18%) in the detergent treatments of higher
      concentration (> 10 ppm). During acute toxicity studies, cakes (LC50 = 6.69 -
      19.98ppm) were found more toxic than powders (LC50 = 18.34-20.72ppm). In
      comparison to the control fish, RBC counts decreased (12-64%) in the detergent
      exposed fish, being more pronounced among those exposed to cakes. The chronic
      exposure (30 days) of the fish also resulted in reduction in the RBC counts (41
      58%). It is thus evident that all the four detergents are toxic to the fish
      Gambusia affinis.

PMID- 16649616
TI  - Methanogenic activity test as an aid in evaluating performance and stability of
      anaerobic bioreactors.
AB  - The correlation between methanogenic activity and anaerobic reactor performance
      is intuitive. In this paper, an attempt has been made to suggest a new parameter,
      defined on the basis of the relative activity of acetoclastic and hydrogen
      oxidising methanogens, to aid in evaluating the performance and stability of
      anaerobic reactors. Performance of three bench scale reactors was assessed at
      different relative populations of the trophic groups of methanogens as estimated
      through acetoclastic and total methanogenic activity tests. Results indicated
      that the acetoclastic to total methanogenic activity ratio 0.7 yielded stable and
      optimal reactor performance. The acetoclastic and total methanogenic activity
      tests provide a simple technique that may aid in evaluating the performance and
      stability of anaerobic bioreactors.

PMID- 16649617
TI  - Role of bougainvilleas in mitigation of environmental pollution.
AB  - Environmental pollution adversely affects health of the people.
      Industrialization, urbanization, over exploitation of natural resources and
      increasing number of automobiles have aggravated the pollution manifold though
      there are various ways to mitigate the environmental pollution. Bio-remediation
      by using selected plant species is an effective method to control pollution which
      is universally accepted. Bougainvillea is a pollution tolerant plant and can help
      in the mitigation of air pollution besides its ornamental value in the
      landscaping. From the rich germplasm collection in NBRI Botanical Garden,
      tolerant plants have been experimented for road side plantation in view of
      mitigating the environmental pollution.

PMID- 16649618
TI  - Dust pollution: effect of grain size in the transportation and deposition by
      wind.
AB  - Study of movement of dust and sand by wind to far off places is seldomly reported
      in literature. To overcome this problem, modelling was done and investigations
      were carried out under reasonable physical constraints. After conducting a
      theoretical analysis, an outcome is reported in this paper which cues for a need
      of further study.

PMID- 16649619
TI  - Contamination of water due to major industries and open refuse dumping in the
      steel city of Orissa--a case study.
AB  - Contamination of ground water is common in the areas surrounded by industrial
      refuse dumping sites and the probability of contamination is more where dumping
      is done in low lying areas and the rate of percolation through the soil is high.
      In order to assess the ground water pollution by leachate around the refuse
      dumping site, eighteen wells were selected for study. Few wells are nearer to the
      dumps, few are far away and others are in between. Also an attempt has been made
      to evaluate the effect of industrial effluents on the ground and surface water
      due to Integrated Rourkela Steel Plant and other major industries. From the
      analytical data of physico-chemical parameters, it is indicated that the river
      water is contaminated mainly due to the industrial and municipal effluents and
      the ground water of some of the analyzed areas is contaminated due to municipal
      and industrial solid waste dumping.

PMID- 16649620
TI  - Physico-chemical characteristics of paper industry effluents--a case study.
AB  - This paper presents the characteristics of wastewater from a small paper mill
      which is using wastepaper as a raw material. After analysis it was found that the
      raw wastewater consisted of 202-294 mg/l and 2010-3200 mg/l of suspended and
      dissolved solids respectively while pH varied from 6.7-7.3. The BOD and COD
      values ranged from 210-310, 1680-2340 mg/l respectively. Due to the treatment of
      raw effluent, the SS and TDS of treated effluent were significantly decreased and
      the values ranged in between 118 mg L(-1) to 154 mg L(-1) and 645 mg L(-1) to 925
      mg L(-1), respectively. The pH values of the treated effluent were higher than
      the raw effluent. The nitrogen, phosphorous and potassium content of treated
      effluent were found to be higher after the treatment of paper mill raw effluent.
      The low amount of nutrient content may be because of the use of chemicals in
      process section which do not contain such elements. The sodium, calcium and
      magnesium were found higher in treated effluent, which may be due to addition of
      chemicals during the pulping and production section.

PMID- 16649621
TI  - Water quality status of Murda village in Ramtek tehsil.
AB  - Major concern for the tribals, residing at Murda village in Ramtek tehsil, has
      always been assumed to be the contaminated drinking water. It has been frequently
      reported that adults and children of this village possess white patches on hands
      due to consumption of this contaminated water. In this context, an attempt has
      been made to assess the water quality of Murda village so as to find out the
      effective solutions. The paper highlights the studies carried out to assess the
      quality of drinking water supplied to the village Murda and its impacts, on the
      habitants.

PMID- 16649622
TI  - Cleaner technology development--some practical steps for developing countries.
AB  - Cleaner technologies often originate from developed countries. Little
      developmental work is continued on the products sourced from developing
      countries. These products are by and large low value products generating large
      quantities of hazardous waste per unit of production. Methodology is proposed for
      phasing out such dirty technologies! products. The development of cleaner
      technologies is proposed for utilizing large quantity of hazardous waste
      generated from identified manufacturing process.

PMID- 16649623
TI  - Phytostabilisation of tailing dams: a quantification of physiological and
      biological responses in plants.
AB  - Effect of unamended and variously amended tailings of Rajpura-Dariba mines,
      Udaipur, India was studied on certain physiological and biochemical responses of
      plants. Plants grown in unamended tailings, showed reduction in shoot-root
      length, shoot-root dry weight, chlorophyll content and an increase in total
      phenol contents and peroxidase activity. Ameliorations resulted in an increase in
      growth and chlorophyll contents, a decrease in total phenol contents and
      reduction in peroxidase activity in the test plants.

PMID- 16649624
TI  - Impact of gutkha chewing & smoking on microbial environment of oral cavity: a
      case study on slum dwellers of selected areas in Visakhapatnam.
AB  - Oral diseases are still a neglected epidemic. During the recent years, in India,
      both in urban and rual, consumption of tobacco in the form of direct chewing of
      gutkha is alarmingly increasing especially in the young adults as which is major
      reason for subsistence of oral cancer. In the present investigation an attempt
      was made to find out the relationship between gutkha chewing including smoking
      and oral micro flora in some slum dwellers of Visakhapatnam. The subjects were
      randomly selected and their health data was collected by distributing
      questionnaire to control and effected subjects. The oral saliva samples were
      collected from both gutkha chewers, smokers and from control groups by using
      saline swabs and inoculated on suitable nutrient media. The results revealed that
      decrease in salivation and mucous formation in gutkha chewers, which further
      resulted in reduction in number of oral micro flora. Aspergillus species appeared
      only in gutkha chewers and smokers. Gutkha chewing and smoking thus, may lead to
      an increase in the oral pathogens by reducing the normal symbiotic microbial
      flora.

PMID- 16649625
TI  - Study of Serum Cholinesterase levels in fish Clarias batrachus (Linn.) exposed to
      pesticides carbaryl and phorate.
AB  - Study of the Serum Cholinesterase levels (SchE) in the freshwater catfish Clarias
      batrachus when exposed to sub lethal dose of pesticides phorate and carbamate,
      was attempted in this paper. SchE levels decreased in the fish exposed to both
      the pesticides, the depletion being more pronounced with phorate. These results
      can be due to impairment of nervous system, liver damage as well as myocardial
      infarction. Similar findings were not only reported in experimental organisms but
      also found in human beings working in agricultural fields and pesticide
      manufacturing plants. Hence it is imperative that suitable occupational health
      and preventive measures need to be undertaken.

PMID- 16649626
TI  - Fe(II) speciation and its uptake by free and immobilized cells of Pseudomonas
      fluorescens from industrial waste water.
AB  - Studies are carried out to remove Fe(II) from wastewater using free and
      immobilized cells of Pseudomonas fluorescens. Experiments are carried out with
      free cells between 6 and 8 pH and the uptake of Fe(II) is observed to be maximum
      at pH 7. Further experiments are done at pH 7. Studies with free and immobilized
      cells revealed that immobilized cells are more efficient for the removal of
      Fe(II) than free cells. Fe(II) uptake with Pseudomonas fluorescens is also
      investigated after the addition of NaCl and MgCl2 to the cells. It is found that
      the uptake has increased when Sodium chloride (NaCl) and Magnesium Chloride
      (MgCl2) mixed cells are used. Effect of deficiency of nutrients is also studied.
      It is found that glucose deficient conditions inhibit Fe(II) uptake more than
      yeast extract deficient ones. pH also plays an important role in the transport of
      Fe(II) across the membrane of the cells.

PMID- 16649627
TI  - Defluoridation studies using laterite material.
AB  - Defluoridation by adsorption process is well known technique. Though several
      established techniques are available, they are found to be expensive and labour
      intensive. Keeping this in view, a study is being done to remove excess fluoride
      in drinking water based on the concept of adsorption using locally available
      materials like laterite, sand and gravel. The studies were being conducted in a
      column with varying depths of laterite by keeping constant gravel depth. The flow
      is varied for all the depths and the results obtained were found to be quite
      encouraging as compared to some of the established costly techniques. This
      technique can be employed in rural areas and places where expensive techniques
      like electrolytic precipitation, etc. cannot be adopted.

PMID- 16649628
TI  - A field study and continuous removal of fluoride in a packed column.
AB  - The synthetic water performance in the light of fluoride removal was studied and
      compared with the actual fluoride contaminated water of different selected water
      collection stations. An indegeneous activated alumina was used as adsorbent. The
      performance of the column for fluoride contaminated water was about 94% fluoride
      reduction at a pH value of 7.0 and the presence of total dissolved solids
      (T.D.S.). 2114 mg/L in subsoil water decreased the fluoride removal by 5%.

PMID- 16649629
TI  - Adsorptive removal of basic dyes from aqueous phase onto activated carbon of used
      tea leaves: a kinetic and thermodynamic study.
AB  - Activated carbon has been prepared from used tea leaves impregnated with H3PO4
      (50%, w/v) and carbonized at 300 degrees C. Its adsorption capacity has been
      tested for the decolourisation of wastewater containing malachite green and
      methylene blue. The effect of system variables such as concentration,
      temperature, pH, contact time, adsorbent dosage and particle size was studied.
      The optimum pH range is 8-10 and dosage required is 1.2 g/L for 100% removal of
      both malachite green and methylene blue (100 mg/L). Break-through and exchaustive
      capacities for malachite green and methylene blue are 300.0 and 314.7 mg/g; 275.0
      and 290.4 mg/g, respectively. The adsorption data follow Langmuir model as well
      as Freundlich model.

PMID- 16649630
TI  - The impact of physical stresses on the growth of cyanobacterium Spirulina
      platensis-S5.
AB  - Cyanobacterium Spirulina is in ever increasing demand internationally due to its
      high value bio-chemical constituents which find application in areas like health
      foods and therapeutics, especially for its high protein content. The Spirulina
      protein is superior to practically all proteins including those from legumes, and
      is comparable to milk proteins for that matter. Moreover, interest in its
      phycocyanin, b-carotene, polyunsaturated acids (PUFA) and super oxide dismutase
      (SOD) contents has attracted the attention of researchers the world over towards
      protecting, promoting and preserving the production of this useful micro
      organism. The present investigation deals with examining the impact of various
      physical stresses viz. intensity and photo-period of light, varying chromatic
      regimes, temperature, pH, etc., on the growth of Spirulina platensis-S5 to spell
      the appropriate conditions for raising the strain in laboratory. No earlier
      report of this kind is available, so far, to our knowledge. The experimental
      results suggested that 16 : 8 hours light : dark regime at light intensity of
      2000 +/- 200 lux, temperature of 30 +/- 1 degrees C and pH of 9.1 are the optimal
      growth conditions for the test micro-organisim. The growth under different
      chromatic regimes observed the order yellow> red> green> blue.

PMID- 16649631
TI  - Persistence and degradation of metalaxyl, mancozeb fungicides and its metabolite
      ethylenethiourea in soils.
AB  - The degradation pattern of metalaxyl, mancozeb and its metabolite
      ethylenethiourea (ETU) residues indicated a close correspondence to first order
      exponential degradation kinetics in soils. Degradation of fungicides in soils was
      predominantly biological as well as chemical in nature. Slower degradation
      ofmetalaxyl was noticed in the soils and their half-life values were higher than
      mancozeb and ETU as evident by wide range of half-life values from 41.24 to
      165.11 days. In case of metalaxyl, Hiriyur soil was found to be superior in
      degrading the metalaxyl. Lower persistence of mancozeb and ETU was observed in
      soils resulting in rapid rate of degradation at smaller half-life values as
      compared to metalaxyl indicating the faster degradation of mancozeb and ETU. In
      mancozeb applied soils, the ETU formation was increased up to 30 days of
      incubation and thereafter it declined. Amongsoils, degradation of either mancozeb
      or ETU is not influenced by soil types. However, mancozeb persistence was higher
      in Hiriyur soils than Chettalli and Bangalore soils.

PMID- 16649632
TI  - Wal-Mart's Rx for health care.

PMID- 16649633
TI  - Pfizer's puzzle.

PMID- 16649634
TI  - Quality--at what price?

PMID- 16649635
TI  - Seizing upon ECT's opportunities.

PMID- 16649636
TI  - Let people make their own decisions.

PMID- 16649637
TI  - Ron Manderscheid: still on the scene.

PMID- 16649638
TI  - Letting recovery take root.

PMID- 16649639
TI  - A place to call home, a place to recover.

PMID- 16649640
TI  - Coming together to treat AIDS and mental illness.

PMID- 16649641
TI  - Improving services by holding hands, not pointing fingers.
AB  - Imagine a community with a social detox center decreasing its number of beds,
      along with facing gaps in linkages from detox to outpatient treatment because of
      funding cuts. This results in overcrowded and misused emergency rooms filled with
      intoxicated people, and patients leave before being seen. Law-enforcement needs
      increase to respond to inebriatedpeople on the streets. Community agencies become
      increasingly frustrated and mistrustful of each other. The community essentially
      is in crisis because of substance abuse issues.

PMID- 16649642
TI  - Sometimes it's not a behavioral health diagnosis.

PMID- 16649643
TI  - It's time for a national approach on staff development.

PMID- 16649644
TI  - Before an EHR, you must endure a 'paper cut'.

PMID- 16649645
TI  - Readying for the RHIO revolution.

PMID- 16649646
TI  - Looking at vendors' 'softer side'.

PMID- 16649647
TI  - Policy making's unintended consequences.

PMID- 16649648
TI  - Getting the board on board: Engaging hospital boards in quality and patient
      safety.
AB  - BACKGROUND: Transformational change in health care calls on hospital boards of
      trustees to engage in quality ata level that has never been asked before. Yet
      little research has been conducted regarding the role of hospital governance in
      quality. METHODS: Interviews were conducted with chief executive officers (CEOs)
      and board chairpersons from aconvenient sample of 30 hospitals, representing 14
      states across the United States. The interviews were 30 to 45 minutes in length
      and included approximately 30 questions that were open-ended and ratings based.
      RESULTS: The level of knowledge of landmark Institute of Medicine (IOM) quality
      reports among CEOs and board chairs was remarkably low. Conversely, board chairs
      and CEOs were well attuned to public reporting of quality information. There were
      significant differences between the CEOs' perception of the level of knowledge of
      their board chairs and the board chairs' self-perception. There was a mild
      association between board engagement in quality and hospital performance
      asdefined by their rates in their composite measure of heart failure, heart
      attack, and pneumonia. DISCUSSION: The engagement of hospital boards inquality
      can be enhanced by (1) increasing education on quality to increase the board's
      quality literacy; (2) improving the framing of an agenda for quality; (3) more
      quality planning, focus, and incentives for leadership and governance for quality
      improvement; and (4) greater focus on the patients. Implementing these steps can
      improve a hospital's overall performance.

PMID- 16649649
TI  - Facilitating and impeding factors for physicians' error disclosure: a structured
      literature review.
AB  - BACKGROUND: It is important for physicians to disclose medical errors to
      institutions (for patient safety), to colleagues (for professional learning), and
      to patients (as part of direct patient care), but no comprehensive review of
      factors that may facilitate or impede disclosure has been undertaken. METHODS: A
      MEDLINE search was conducted of English-language articles published from 1975
      2004, with review of bibliographies. A total of 5,509 articles were reviewed by
      title, 881 articles were retrieved for full text review, and 475 articles
      satisfied the inclusion criteria. Article content was assessed by identifying
      factors that facilitate or impede disclosure and classifying each article's
      primary goal of disclosure. RESULTS: Thirty-five factors believed to facilitate
      disclosure were identified (for example, accountability, honesty, restitution),
      as were 41 factors believed to impede it (for example, professional
      repercussions, legal liability, blame). The three most common goals of disclosure
      were to improve patient safety, enhance learning, and inform patients.
      Facilitating factors were more commonly cited when the goal of disclosure was to
      inform patients. DISCUSSION: A wide range of factors are capable of facilitating
      or impeding the disclosure of medical errors. Innovations to enhance error
      disclosure should address both sides of the equation: impeding factors should be
      removed and facilitating factors should be promoted.

PMID- 16649650
TI  - Using telemedicine to facilitate thrombolytic therapy for patients with acute
      stroke.
AB  - BACKGROUND: Recent stroke-care requirements state that all stroke patients should
      be screened for intravenous recombinant tissue plasminogen activator (rt-PA) and
      treated, if the appropriate inclusion and exclusion criteria are met. Two
      community hospitals 90-130 miles east of Houston deployed telemedicine
      (videoteleconferencing) to provide acute stroke consultative services. DEVELOPING
      A TELEMEDICINE CAPACITY: According to the Brain Attack Coalition's
      recommendations, neurosurgical services need to be accessible within two hours.
      Given their incomplete neurology coverage, the remote-site hospitals identified
      telemedicine as the best option, with the University of Texas Health Science
      Center at Houston stroke team as the provider of expertise. RESULTS: In the 13
      months preceding the telemedicine project (January 2003-March 2004), 2 (.8%) of
      327 patients received rt-PA, compared with 14 (4.3%) of 328 patients during the
      telemedicine project (April 2004-May 2005), p < .001). Seven patients had > or =
      4 points improvement in a stroke scale at 24 hours posttreatment. Three patients
      worsened during the 24-hour assessment. No intracerebral hemorrhages occurred.
      Door-to-needle median time was 85 minutes (range, 27-165 minutes). DISCUSSION:
      Telemedicine facilitated thrombolytic therapy for acute stroke patients and is
      intended not to replace care provided by remote-site providers but rather to
      address a time- and spatially related emergency need.

PMID- 16649651
TI  - Diabetes-related foot care at 10 Veterans Affairs medical centers: must do's
      associated with successful microsystems.
AB  - BACKGROUND: Well-coordinated interdisciplinary preventive foot care has been
      reported to significantly reduce diabetes-related foot ulcers, amputations, and
      hospitalization. However, the contribution of the specific components leading to
      these "successes" is not fully characterized. The microsystem conceptual
      framework was adapted to foot care to determine which of the microsystem success
      characteristics were associated with decreased major lower-limb amputation rates
      at 10 Veterans Affairs (VA) medical centers. METHODS: Two-day site visits were
      conducted using standardized interviews at the 10 VA medical centers. RESULTS:
      Six "must do's" for foot care in microsystems were correlated at > or = (-.30)
      with amputation rates: (1) addressing all foot care needs, (2) appropriate
      referrals, (3) ease in recruiting staff, (4) confidence in staff, (5) available
      stand alone specialized diabetic foot care services, and (6) providers attending
      diabetic foot care education in the past three years. Using multiple linear
      regression, the sum of these items described 59% of the variance (p = 0.006).
      DISCUSSION: Clinicians and managers may want to include the must-do's in system
      modifications to improve foot care for people with diabetes. Many of the sites
      displayed exemplary features in foot care, such as providing a formal orientation
      to the foot care clinics.

PMID- 16649652
TI  - Operating manual-based usability evaluation of medical devices: an effective
      patient safety screening method.
AB  - BACKGROUND: Use of medical devices often directly contributes to medical errors.
      Because it is difficult or impossible to change the design of existing devices,
      the best opportunity for improving medical device safety is during the purchasing
      process. However, most hospital personnel are not familiar with the usability
      evaluation methods designed to identify aspects of a user interface that do not
      support intuitive and safe use. A review of medical device operating manuals is
      proposed as a more practical method of usability evaluation. METHOD: Operating
      manuals for five volumetric infusion pumps from three manufacturers were selected
      for this study (January-April 2003). Each manual's safety message content was
      evaluated to determine whether the message indicated a device design
      characteristic that violated known usability principles (heuristics) or indicated
      a violation of an affordance of the device. RESULTS: "Minimize memory load," with
      65 violations, was the heuristic violated most frequently across pumps.
      Variations between pumps, including the frequency and severity of violations for
      each, were noted. DISCUSSION: Results suggest that manual review can provide a
      proxy for heuristic evaluation of the actual medical device. This method,
      intended to be a component of prepurchasing evaluation, can complement more
      formal usability evaluation methods and be used to select a subset of devices for
      more extensive and formal testing.

PMID- 16649653
TI  - A data flow sheet for managing unstable patients in the emergency department.
AB  - The one-page data flow sheet for emergency care can facilitate rapid review of
      ongoing care and transfer of information for the next care givers.

PMID- 16649654
TI  - Reconciliation failures lead to medication errors.
AB  - Poor communication of medical information at transition points of care--at
      admission, transfer, and discharge--often results in medication errors, but
      various strategies can reduce the likelihood of error.

PMID- 16649655
TI  - Using medication reconciliation to prevent errors.

PMID- 16649656
TI  - [Ancient DNA].
AB  - The review is devoted to molecular genetic studies of ancient DNA. The problems
      of DNA preservation and modification after cell death, as well as techniques of
      working with ancient DNA, including its retrieval, removal of inhibitors, PCR
      amplification, and phylogenetic analysis, are discussed in detail. The
      possibilities are considered of using ancient DNA in resolving issues of
      systematics and evolution of various animal taxa, population genetics of humans
      and rare species, taxonomic identification and paleontological reconstructions,
      geographic origin of populations, microbiological analysis of paleontological and
      archeological finds, as well as some humanitarian aspects of its use.

PMID- 16649657
TI  - [Uncontrolled genetic processes in artificial populations: proving the leading
      role of selection in evolution].
AB  - The review considers studies examining artificially maintained populations as
      models for understanding biological evolution. The key factors of gene pool
      evolution-random processes, interspecific hybridization, migration, mutation, and
      selection--are analyzed. We present evidence indicating that selection is the
      leading evolutionary factor that regulates the operation of other factors,
      directly or through genetic systems.

PMID- 16649658
TI  - [Speciation in bacteria: comparison of the 16S rRNA gene for closely related
      Enterococcus species].
AB  - Sequencing of the 16S rRNA genes from enterococcal strains used as starters
      suggested the existence of specialized taxa of lactic acid enterococci within the
      species Enterococcus durans and E. faecium and a new species, E. lactis.
      Comparisons showed that the 16S rRNA genes of closely related species have the
      same sets of variable positions with different combinations of nucleotides. The
      presence of identical combinations of nucleotide substitutions in different
      species was assumed to result from a transfer of genetic information via gene
      conversion between different rRNA operons. Such events were presumably associated
      with speciation in bacteria.

PMID- 16649659
TI  - [Antirestriction and antimodification activities of the ArdA protein encoded by
      the IncI1 transmissive plasmids R-64 and ColIb-P9].
AB  - Proteins of the Ard family are specific inhibitors of type I restriction
      modification enzymes. The ArdA of R64 is highly homologous to ColIb-P9 ArdA,
      differing only by four amino acid residues of the overall 166. However, unlike
      ColIb-P9 ArdA, which inhibits both the endonuclease and the methylase activities
      of EcoKI, the R64 ArdA protein inhibits only the endonuclease activity of this
      enzyme. The mutant forms of R64 ArdA--A29T, S43A, and Y75W, capable of partially
      reversing the protein to ColIb-P9 ArdA form--were produced by directed
      mutagenesis. It was demonstrated that only Y75W mutation of these three variants
      essentially influenced the functional activity of ArdA: the antimodification
      activity was restored to approximately 90-99%. It is assumed that R64 ArdA
      inhibits formation of the complex between unmodified DNA and the R subunit of the
      type I restriction-modification enzyme EcoKI (R2M2S), which translocates and
      cleaves DNA. ColIb-P9 ArdA protein is capable of forming the DNA complex not only
      with the R subunit, but also with the S subunit, which contacts sK site
      (containing modified adenine residues) in DNA. ArdA bound to the specific sK site
      inhibits concurrently the endonuclease and methylase activities of EcoKI (R2M2S),
      while ArdA bound to the nonspecific site in the R subunit blocks only its
      endonuclease activity.

PMID- 16649660
TI  - [Molecular evidence for the lysogenic state of microorganisms belonging to the
      genus Bordetella and characterization of Bordetella parapertussis temperate
      bacteriophage 66(2.2)].
AB  - A new bacteriophage phiK of microorganisms belonging to the genus Bordetella was
      isolated from cells of the earlier characterized strains 66(2-2) (1 and 2)
      obtained upon phage conversion of B. parapertussis 17903 cells by B. pertussis
      bacteriophage phi134. Bacteriophage phiK is identical to previously described
      Bordetella bacteriophages phiT, phi134, and phi214 in morphology and some
      biological properties but has a permuted genome different from all other phages.
      DNA of bacteriophage phiK is not integrated in the chromosome of B. parapertussis
      17903, similar to DNA of bacteriophages phiT, phi134, and phi214 that are not
      integrated into B. pertussis and B. bronchiseptica chromosomes, but may be
      present in a small part of the bacterial population as linear plasmids. Sequences
      homologous to DNA of bacteriophage phiK were detected in the chromosome of strain
      66(2-2) (1 and 2) and in chromosomes of all tested strains B. pertussis and B.
      bronchiseptica. Prophage integration in chromosomes of microorganisms of the
      genus Bordetella may vary in different bacterial strains and species. An
      assumption about abortive lysogeny of B. parapertussis bacteria for phiK phage
      and of B. bronchiseptica for closely related phages phiT, phi134, and phi214 has
      been advanced. The possibility of involvement of B. pertussis insertion sequences
      in the formation of the chromosomal structure in 66(2-2) convertants and in phage
      genomes is considered.

PMID- 16649661
TI  - [Genetic divergence in pink salmon introduced into the European north of Russia:
      microsatellite and allozyme variation analysis].
AB  - The 1985 introduction into the European North of Russia resulted in the formation
      of a large stock of pink salmon of the odd-year breeding line. To assess the
      divergence of the new population and the role of various microevolutionary
      factors, variation of four microsatellite loci and fifteen genes encoding
      proteins (allozymes) in samples of fish, running for spawning in rivers of the
      new area, and in samples from the donor population of the Ola River (Magadan
      oblast). In the generations 8 and 9 of the introduced pink salmon of the odd-year
      line, the genetic diversity (the number of alleles and the mean heterozygosity)
      both at allozyme and at microsatellite loci was significantly lower, than that in
      the donor population. The explanations of the decline in diversity are discussed.
      The first evidence for spatial genetic divergence in transplanted fish within the
      new area has been obtained; the divergence level may be comparable with that
      characteristic of native populations.

PMID- 16649662
TI  - [Abnormal meiosis in bisporic mutants of white button mushroom Agaricus bisporus
      (Lange) Imbach].
AB  - A formerly developed method of obtaining spread preparations of mushroom basidial
      nuclei was applied to study of meiotic prophase I in bisporic white button
      mushroom (Agaricus bisporus) strains. Meiotic recombination and assemblage of
      axial structures (axial elements and synaptonemal complexes) of chromosomes in
      meiotic prophase I are interrelated. It is known that the frequency of meiotic
      recombination is reduced in the bisporic A. bisporus variety. We showed that
      formation of axial structures of meiotic chromosomes in bisporic strains of this
      mushroom was disrupted. The phenotypes of disruptions in spread prophase nuclei
      are diverse. In leptotene and early zygotene, many nuclei contain abnormal, often
      short, and, as a rule, few chromosomal axial elements. The abnormalities in the
      formation of synaptonemal complexes at the zygotene-diplotene stage are of the
      same kind and even more pronounced. We discovered an important feature of meiosis
      in A. bisporus associated with fruit-body morphogenesis. Meiosis starting in
      basidia (meiocytes) of young closed fruit bodies is accompanied by disruption of
      chromatin condensation in prophase I and, probably, is arrested. After indusium
      breakage, the course of meiosis normalizes. Preparations with clearly observable
      chromosomal axial structures can be obtained only at this stage of fruit-body
      development.

PMID- 16649663
TI  - [Genetic control of dwarfism in hexaploid triticale (Triticosecale Wittm.)].
AB  - The genetic control of plant height has been studied in hexaploid forms of
      triticale (2n = 42) with genomic structure AABBRR. Thirty-four specimens from the
      world collection of triticale at the Vavilov All-Russian Research Institute of
      Plant Breeding with plant heights from 70 to 180 cm have been used in the study.
      The hybrid analysis of the first, second, and third generations, as well as
      backcross offsprings, has demonstrated that the given trait is characterized by
      different modes of inheritance: dominance of dwarfism, dominance of tallness, and
      intermediate inheritance. It has been found that triticale cultivars of middle
      and large height differ from short ones in alleles of one or two major genes.

PMID- 16649664
TI  - [Genetic control of effective juvenile resistance to leaf rust in collection
      accessions of Triticum aestivum L].
AB  - Of 153 accessions reported to be resistant to leaf rust (Puccinia recondita Rob.
      ex. Desm.), only 70 were not affected by a pooled P. recondita population.
      According to phytopathological tests (inoculation with test clones), 14
      accessions contained the Lr19 gene; 36, the Lr24 gene; 1, the Lr41 gene; and 19
      presumably had the Lr9 gene. The presence of these resistance genes was confirmed
      by hybrid analysis for 26 accessions. Of 28 accessions reported to carry new
      effective resistance genes other than the known genes, 23 were affected by the P.
      recondita population. In four of the other five accessions, resistance proved to
      be controlled by known genes. Possible causes of false identification of new
      effective leaf rust resistance genes in wheat are discussed.

PMID- 16649665
TI  - [Genetic analysis of toxic ion tolerance in barley].
AB  - The genetic control of high tolerance of toxic aluminum ions in barley Hordeum
      vulgare L. has been studied. Cultivar Faust I (c-24612) and accession 9736 from
      Karelia have been compared with aluminum-sensitive cv. Colsess IV (accession c
      24626). Analysis of F1, F2BC1, F3, and F4 progenies has shown that the
      development of roots of cv. Faust I in water medium with aluminum ions is
      determined by one (AlpF1) or two (AlpF1, AlpF2) genes. The development of roots
      of accession 9736 is determined by two genes, AlpK1 and AlpK2. The genes have not
      been not tested for nonidentity. The high tolerance of Faust I shoots are
      determined by one major tolerance factor and one dominant inhibitor gene, which
      hampers the manifestation of the dominant tolerance gene. The penetrance of the
      inhibitor gene may be incomplete. The aluminum sensitivity of roots and 7-day
      shoots of cv. Faust I is determined by different genetic factors. The response of
      barley plants to aluminum ions may be determined by small-effect genes.

PMID- 16649666
TI  - QTL mapping analysis of plant height and ear height of maize (Zea mays L.).
AB  - Genetic map containing 103 microsatellite loci obtained on 200 F2 plants derived
      from the cross R15 x 478 was used for quantitative trait loci (QTL) mapping in
      maize. QTL were characterized in a population of 200 F2:4 lines, derived from
      selfing the F2 plants, and were evaluated with two replications in two
      environments. QTL determinations were made from the mean of these two
      environments. Plant height (PH) and ear height (EH) were measured. Using
      composite interval mapping (CIM) method, a total of 14 distinct QTLs were
      identified: nine for PH and five for EH. Additive, partial dominance, dominance,
      and overdominance actions existed among all detected QTL affecting plant height
      and ear height. The QTL explained 78.27% of the phenotypic variance of PH and
      41.50% of EH. The 14 QTLs displayed mostly dominance or partial dominance gene
      action and mapped to chromosomes 2, 3, 4, 8 and 9.

PMID- 16649667
TI  - Genetic diversity of Triticum turgidum L. based on microsatellite markers.
AB  - Using microsatellite (SSR) markers, the genetic diversity and genetic
      relationships among 48 Triticum turgidum L. accessions, including 30 Triticum
      turgidum L. ssp. turgidum, 7 Triticum turgidum L. ssp. durum, 4 Triticum turgidum
      L. ssp. carthlicum, 3 Triticum turgidum L. ssp. paleocolchicum, 2 Triticum
      turgidum L. ssp. turanicum and 2 Triticum turgidum L. ssp. polonicum accessions,
      were investigated. A total of 97 alleles were detected on 16 SSR loci. At each
      locus, the number of alleles ranged from 2 to 14, with an average of 6.1. The
      Genetic similarity (GS) value ranged from 0.20 to 0.92, with the mean of 0.59. In
      cluster analysis, it was found the 48 Triticum turgidum L. accessions could be
      distinguished easily by SSR markers, whereas the 6 subspecies taxonomic entities
      of T. turgidum L. could not differentiate with each other, indicating that the
      morphological differences present among the 6 subspecies could not be reflected
      by the SSR markers. These results suggested that SSR markers had the superiority
      in detecting the genetic diversity of T. turgidum L., while it was not good for
      the studies of the phylogenic relationships among the subspecies of T. turgidum
      L.

PMID- 16649668
TI  - [Diversity of wild and domestic pig populations estimated by a set of serum
      allotypes].
AB  - Variation of serum protein allotypes serving as genetic markers of the blood has
      been analyzed in 29 populations of the domestic pig and subspecies of the wild
      boar. The population biodiversity and genetic structure have been estimated by
      two methods: by the frequencies of allotype combinations and with the use of a
      map constructed in the space of two principal components. The results obtained
      are the basis for determining the characteristics of the microevolution of wild
      boars and formation of the breeds of domestic pigs.

PMID- 16649669
TI  - [Polymorphism of dental formula and segregation of its variants in a pedigree of
      kerry blue terrier dogs].
AB  - Polymorphism of the dental formula was analyzed in a sophisticated pedigree of
      Kerry Blue Terrier. A lack of one or more lower premolars was observed in some
      dogs. Two different patterns of missing teeth were identified. One pattern
      consisted in agenesis of a second premolar, often in combination with agenesis of
      neighbor teeth, including the fourth premolar. In the second pattern, agenesis of
      a fourth premolar was expressed as an isolated abnormality. It was shown
      previously that the first pattern is inherited as a recessive trait with near
      complete penetrance. In this work, the control of a major-gene was demonstrated
      for the second pattern. This abnormality develops in 70-80% of mutant homozygotes
      and in no more than 20% of heterozygotes and wild-type homozygotes. It was shown
      that the two dentition abnormalities are controlled by different genes, which
      were designated LPA2 and LPA4 (Lower Premolar Agenesis).

PMID- 16649670
TI  - [Analysis of the hemochromatosis gene (HFE) mutations, C282Y and H63D, in the
      populations of Central Asia].
AB  - Analysis of the C282Y and H63D mutations in the HFE gene was carried out in 594
      individuals representing seven indigenous populations of Central Asia. Among the
      populations examined, mutation C28Y was found in Uighurs with the frequency of
      0.009, and in Kazakhs and Tajiks with the frequency of 0.012. The mutation was
      absent in Uzbeks, Kyrgyzes, Kurds, and Turkmens. Mutation H63D was detected in
      all populations studied with the frequencies ranging from 0.024 (Tajiks) to 0.139
      (Turkmens). Judging by the frequencies of the mutations of interest, the
      populations examined occupied the intermediate position between the European and
      Eastern Asian populations, which corresponded to their geographical position.

PMID- 16649671
TI  - [Changes in litter size in Kerry blue terrier dogs with abnormal dentition].
AB  - The pleiotropic effects of mutations resulting in abnormal dentition were
      analyzed in Kerry Blue Terrier. A decrease in litter size was demonstrated for
      dogs with dentition anomalies. The mean litter size was 5.72 puppies when both
      parents had normal dentition and 3.64 puppies when the parents had hypodontia.
      Analysis showed that the decrease in litter size cannot be fully explained by the
      effect of inbreeding and is most probably associated with the pleiotropic effect
      of the genes controlling teeth development on the embryonic viability.

PMID- 16649672
TI  - Stem cells that kill.

PMID- 16649673
TI  - Estrogen again.

PMID- 16649674
TI  - Mother-infant research informs mother-infant treatment.
AB  - A brief mother-infant treatment approach using "video feedback" is described.
      This approach is informed both by psychoanalysis and by research on mother-infant
      face-to-face interaction using video microanalysis. Two cases are presented. In
      the first, descriptions of the videotaped interactions which informed the
      interventions are presented. In the second, knowledge of mother-infant
      microanalysis research informed the treatment, even though videotaping was not an
      option. The respective "stories" of the presenting complaints, the video
      interaction, and the parent's own upbringing are linked. Specific representations
      of the baby that may interfere with the parent's ability to observe and process
      her nonverbal interaction with her infant are identified. The mother has a
      powerful experience during the video feedback of watching herself and her baby
      interact. Our attempts together to translate the action-sequences into words
      facilitates the mother's ability to "see" and to "remember", fostering a rapid
      integration of implicit and explicit modes of processing.

PMID- 16649675
TI  - "What is genuine maternal love"? Clinical considerations and technique n
      psychoanalytic parent-infant psychotherapy.
AB  - The question of what is genuine maternal love was posed by a mother struggling to
      understand and value the nature of her bond with her small baby. The question
      surfaced time and again in the context of this dyad's long-term parent-infant
      psychotherapy and has challenged me to examine my thinking and, indeed, has
      produced impassioned discussions within the Parent Infant Project team at The
      Anna Freud Centre. In this paper I will address this question through sessional
      material of this mother and baby and discuss issues of technique in response to
      it, including my countertransference and conceptualization.

PMID- 16649676
TI  - Minding the baby a reflective parenting program.
AB  - Minding the Baby, an interdisciplinary, relationship based home visiting program,
      was initiated to help young, at-risk new mothers keep their babies (and
      themselves) "in mind" in a variety of ways. The intervention--delivered by a team
      that includes a nurse practitioner and clinical social worker--uses a
      mentalization based approach; that is, we work with mothers and babies in a
      variety of ways to develop mothers' reflective capacities. This approach--which
      is an adaptation of both nurse home visiting and infant-parent psychotherapy
      models--seems particularly well suited to highly traumatized mothers and their
      families, as it is aimed at addressing the particular relationship disruptions
      that stem from mothers' early trauma and derailed attachment history. We discuss
      the history of psychoanalytically oriented and attachment based mother-infant
      intervention, the theoretical assumptions of mentalization theory, and provide an
      overview of the Minding the Baby program. The treatments of two teenage mothers
      and their infants are described.

PMID- 16649677
TI  - "In a black hole": the (negative) space between longing and dread: Home-based
      psychotherapy with a traumatized mother and her infant son.
AB  - This paper offers fragments from the first year of a home-based mother-baby
      psychotherapy, in which I attempted to help a traumatized and dissociated mother
      to emotionally engage with her infant son. The treatment was organized in part
      around certain developmental objectives common to both attachment and
      psychoanalytic theory. These include: The ability to name and metabolize
      feelings, to evoke a soothing maternal introject, and to relate to the partner's
      mind as a separate, understandable center of initiative and intention. In
      addition, attachment theory, with its emphasis on the critical psychobiological
      role of containing fear and distress in infancy, was a useful guide in
      formulating the treatment. The paper reviews research findings on mother-infant
      pairs described as frightened-disorganized, discusses some of the challenges
      encountered in home-based mother-infant psychotherapy and then discusses the case
      of Mary and John. The case illustrates how mother-infant psychotherapy may
      interrupt the intergenerational transmission of disorganized attachment by
      working within the couple to name, metabolize and flexibly respond to painful,
      dissociated or frightening experiences.

PMID- 16649678
TI  - Herding the animals into the barn: a parent consultation model.
AB  - Initial assessments of children with psychological problems are important both to
      develop appropriate diagnoses and to provide the basis for productive discussions
      with parents on treatment alternatives. This paper develops an assessment method
      referred to as the Parent Consultation Model (PCM) that emphasizes the use of
      videotape micro-analysis and developmental theory to provide critical information
      to parents as well as to the clinician in this important initial stage. The paper
      provides a description of the PCM and an expanded example of the use of the PCM,
      including illustrations of how these methods can be used to organize information
      and engage parents in the initial consultation. The paper concludes with some
      observations on the role of new techniques and ideas in psychotherapy and
      psychoanalysis.

PMID- 16649679
TI  - Recollections of being in child psychoanalysis: a qualitative study of a long
      term follow-up project.
AB  - To date there has been very little research looking at how former child analytic
      patients have made sense of the experience of being in psychoanalytic treatment
      as children. Based on semi-structured interviews with twenty-seven people who, as
      children, had been in intensive psychoanalysis at the Anna Freud Centre, London,
      between 1952 and 1980, this study uses a qualitative methodology to explore two
      central themes: "attitudes toward being in therapy" and "memories of therapy and
      the therapist". This report presents the findings of the study in narrative form,
      and argues that the recollections of former child analytic patients are an
      important, but under-used, source of knowledge for an understanding of the
      psychoanalytic process.

PMID- 16649680
TI  - The process of attachment and autonomy in latency: a longitudinal study of ten
      children.
AB  - The findings in this clinical, longitudinal study describe the process of
      attachment and autonomy as it unfolds during the latency period of development.
      Ten normal boys and girls were studied from ages six through eleven. A separate
      timetable of latency development for boys and girls is suggested. The differences
      in the boys' and girls' separation responses, which include feelings of a lack of
      self-coherence, loss, anger, neediness, movement toward peers and defense
      functioning, are delineated and discussed.

PMID- 16649681
TI  - Play in the psychoanalytic setting: Ego capacity, ego state, and vehicle for
      intersubjective exchange.
AB  - The psychoanalysis of an 8-year-old boy who does not play is presented to
      illustrate the centrality of the "state of playing" for meaning-making and
      communication in treatment. Developmental research links affect regulation,
      narcissistic balance, and the capacity for make-believe to the early inter
      subjective exchange between mother and infant. The intersubjective dialogue
      between patient and analyst in the "state of playing" is a crucial component of
      child analysis and its absence both reflects and compounds ego vulnerability in
      the child and presents a daunting technical challenge to the analyst.

PMID- 16649682
TI  - Psychoanalysis as cognitive remediation: Dynamic and Vygotskian perspectives in
      the analysis of an early adolescent dyslexic girl.
AB  - The interface of neurocognitive problems and dynamic concerns are examined in the
      treatment of an early adolescent dyslexic girl. Despite previous intensive
      remediation, she had been unable to master reading and spelling, but made
      remarkable progress after a relatively brief period of psychoanalysis.
      Psychoanalytic and Vygotskian perspectives are integrated to provide a model of
      how play, within the analytic context, is mutative for learning disabled
      children. Through the process of reexteriorization in the transference, play
      allows for the interpretation and resolution of traumatic situations which have
      become associated with learning. As the act of learning becomes separate from the
      personal and affective context in which it took place, the child gains access to
      other, more normative, functions of play. These functions include the development
      of the capacity to separate meaning from action and the ability to understand
      words as generalized categories which represent objects, rather than being part
      of the specific object named. These two capacities, fundamental to the
      development of abstract thought, will support reflective awareness and help
      modulate affective states. The abilities furthered in play also act to remediate
      one component of dyslexia-the difficulty separating context from more abstract
      bits of knowledge. Finally, the child learns to "play at reality, " often trying
      on the new role of "student". As Vygotsky notes, play is essential in allowing
      the child to become aware of what she knows. For a dyslexic child, for whom
      reading may never become completely a part of procedural memory, becoming
      conscious of what he knows may also enhance mastery of the skills of phonological
      processing, albeit more slowly than normally developing readers. The pleasure in
      play and the repetition it generates aids the internalization of the task and the
      development of automaticity.

PMID- 16649683
TI  - A girl's experience of congenital trauma: The healing function of psychoanalysis
      in the adolescent years.
AB  - This paper addresses the centrality of conflict in psychic trauma, as evidenced
      in the psychoanalytic treatment of an adolescent girl with a congenital life
      threatening and disfiguring condition that necessitated multiple surgical
      procedures in early childhood. The focus is twofold: to elucidate certain
      characteristics of analysis in the adolescent phase that promote the integration
      of early trauma; and to shed light on the modes of therapeutic action of
      psychoanalysis. Case material is presented indicative of the psychic consequences
      of early medical traumata, including the impairment of the ego's capacity to
      utilize anxiety as a signal function that mobilizes defense, the failure of
      repetition to effect mastery of the trauma, the predominant use of aggression in
      the interest of defense, and distortions in self and object representations. The
      author offers evidence to show that conflicts over aggression and oedipal
      desires, characteristic of adolescent girls who have not been subject to trauma,
      were involved in the defensive function of her patient's pervasive sense of
      defectiveness. She postulates that the interpretation of conflict and defense is
      the analyst's attuned response to the mind of the patient, and points to the
      resulting increase in the capacity to observe and to exercise volitional control
      over heretofore unconscious, automatic mental processes as evidence of the
      mutative function of dynamic interpretation.

PMID- 16649684
TI  - Psychoanalytic reconstruction and reintegration.
AB  - Psychoanalytic reconstruction has declined in theoretical and clinical interest
      as greater attention has been directed to the here and now of the transference
      counter-transference field and inter-subjectivity. Transference, however, is
      based upon childhood fantasy, and is a new edition of unconscious intra-psychic
      representation and relationships. In this paper transference is viewed as a guide
      to reconstruction, but transference itself is also an object of reconstruction.
      Reconstruction is a complementary agent of change, which integrates genetic
      interpretations and restores the continuity of the self The patient's childish
      traits, features, fixations, and irrational childish fantasies and behavior point
      to the necessity for reconstruction. Reconstruction organizes dissociated,
      fragmented memories, potentiating the further retrieval of repressed memories.
      Reconstruction is essential to the working through and attenuation of early
      traumatic experience. Recapture of the past is necessary to demonstrate and
      diminish the persistent influence of the past in the present, and to meaningfully
      connect past and present. A case is presented in which reconstruction had a
      central, vital role in the analytic process.

PMID- 16649685
TI  - On foresight.
AB  - Examples of our interest in the future are drawn from poetry, religion, general
      medicine, and from the aims of psychoanalysis. The concept of foresight is taken
      as a focus for questions regarding the relative inattention to a psychology of
      the future in psychoanalytic thought. This inquiry leads to consideration of the
      varying constraints and potentials that are determined by the formal properties
      of verbal language and mental images, which are briefly compared and contrasted
      in regard to their usefulness in understanding complex dynamic systems such as
      psychoanalysis. The paper concludes with questions regarding the qualities of
      conscious and unconscious, and secondary and primary process thought, and with
      comments on technique.

PMID- 16649686
TI  - A new type of threat.

PMID- 16649687
TI  - How a human pandemic could start.

PMID- 16649688
TI  - Survival of the adaptive.

PMID- 16649689
TI  - Leading for the long run.

PMID- 16649690
TI  - Getting straight talk right.

PMID- 16649691
TI  - Pandemic planning checklist for businesses.

PMID- 16649692
TI  - Visualizing your vulnerabilities.

PMID- 16649693
TI  - What to expect from government.

PMID- 16649694
TI  - Limiting exposure--of the legal kind.

PMID- 16649695
TI  - A preview of disruption.

PMID- 16649696
TI  - Staying connected.

PMID- 16649697
TI  - All eyes on China.

PMID- 16649698
TI  - Why innovation in health care is so hard.
AB  - Health care in the United States--and in most other developed countries--is
      ailing. Medical treatment has made astonishing advances, but the packaging and
      delivery of health care are often inefficient, ineffective, and user unfriendly.
      Problems ranging from costs to medical errors beg for ingenious solutions-and
      indeed, enormous investments have been made in innovation. But too many efforts
      fail. To find out why, it's necessary to break down the problem, look at the
      different types of innovation, and examine the forces that affect them. Three
      kinds of innovation can make health care better and cheaper: One changes the ways
      consumers buy and use health care, another taps into technology, and the third
      generates new business models. The health care system erects an array of barriers
      to each type of innovation. More often than not, organizations can overcome the
      barriers by managing the six forces that have an impact on health care
      innovation: players, the friends and foes who can bolster or destroy;funding, the
      revenue-generation and capital-acquisition processes, which differ from those in
      other industries; policy, the regulations that pervade the industry; technology,
      the foundation for innovations that can make health care delivery more efficient
      and convenient; customers, the empowered and engaged consumers of health care;
      and accountability, the demand from consumers, payers, and regulators that
      innovations be safe, effective, and cost-effective. Companies can often turn
      these six forces to their advantage. The analytical framework the author
      describes can also be used to examine other industries. Cataloging the innovation
      types and identifying the forces that aid or undermine them can reveal insights
      on how to treat chronic innovation ills- prescriptions that will make any
      industry healthier.

PMID- 16649699
TI  - Second in command: the misunderstood role of the chief operating officer.
AB  - Asking the question,"What makes a great COO?" is akin to asking "What makes a
      great candidate for U.S. vice president?" It all depends on the first name on the
      ticket--the CEO. New research sheds light on this most contingent, and most
      mysterious, of C-suite jobs. After in-depth conversations with dozens of
      executives who have held the position and with CEOs who have worked with COOs,
      the authors have concluded that different views of the COO role arise from the
      different motives behind creating the position in the first place. There are
      seven basic reasons why companies decide to hire a COO: to implement the CEO's
      strategy; to lead a particular initiative, such as a turnaround; to mentor a
      young, inexperienced CEO; to complement the strengths or make up for the
      weaknesses of the CEO; to provide a partner to the CEO; to test out a possible
      successor; or to stave off the defection of a highly valuable executive,
      particularly to a rival. This tremendous variation implies that there is no
      standard set of great COO attributes, which makes finding suitable candidates
      difficult for companies and recruiters alike. Still, certain common success
      factors came up consistently in the interviews, the most important being building
      a high level of trust between CEO and COO. Trust comes from meeting obligations
      on both sides: The COO must truly support the CEO's vision; keep ego in check;
      and exhibit strong execution, coaching, and coordination skills. The CEO must
      communicate faithfully, grant real authority and decision rights, and not stymie
      the COO's career. It's surprising that COOs are not more common. They would be,
      the authors contend, if there were less confusion surrounding the role. As we
      continue to demystify that role, more companies will benefit from more effective
      leadership.

PMID- 16649700
TI  - Creating new growth platforms.
AB  - Sooner or later, most companies can't attain the growth rates expected by their
      boards and CEOs and demanded by investors. To some extent, such businesses are
      victims of their own successes. Many were able to sustain high growth rates for a
      long time because they were in high-growth industries. But once those industries
      slowed down, the businesses could no longer deliver the performance that
      investors had come to take for granted. Often, companies have resorted to
      acquisition, though this strategy has a discouraging track record. Over time, 65%
      of acquisitions destroy more value than they create. So where does real growth
      come from? For the past 12 years, the authors have been researching and advising
      companies on this issue. With the support of researchers at Harvard Business
      School and Insead, they instituted a project titled "The CEO Agenda and Growth".
      They identified and approached 24 companies that had achieved significant organic
      growth and interviewed their CEOs, chief strategists, heads of R&D, CFOs, and top
      line managers. They asked, "Where does your growth come from?" and found a
      consistent pattern in the answers. All the businesses grew by creating new growth
      platforms (NGPs) on which they could build families of products and services and
      extend their capabilities into multiple new domains. Identifying NGP
      opportunities calls for executives to challenge conventional wisdom. In all the
      companies studied, top management believed that NGP innovation differed
      significantly from traditional product or service innovation. They had
      independent, senior-level units with a standing responsibility to create NGPs,
      and their CEOs spent as much as 50% of their time working with these units. The
      payoff has been spectacular and lasting. For example, from 1985 to 2004, the
      medical devices company Medtronic grew revenues at 18% per year, earnings at 20%,
      and market capitalization at 30%.

PMID- 16649701
TI  - Are leaders portable?
AB  - Does management talent transfer from one company to another? The market certainly
      seems to think so. Stock prices spike when companies announce new CEOs from a
      talent generator like General Electric. But how do these executives perform over
      the long term? The authors studied the careers of 20 former GE executives who
      went on to lead other major organizations, with strikingly uneven results. Even
      the best management talent, the authors found, is transferable only if it maps to
      the challenges of the new environment. More specifically, the authors identified
      five types of skills that may or may not transfer to a new job: general
      management human capital, or the skills to gather, cultivate, and deploy
      financial, technical, and human resources; strategic human capital, or
      individuals' expertise in cost cutting, growth, or cyclical markets; industry
      human capital, meaning the technical and regulatory knowledge unique to an
      industry; relationship human capital, or the extent to which a manager's
      effectiveness can be attributed to his or her experience working with colleagues
      or as part of a team; and company-specific human capital, or the knowledge about
      routines and procedures, corporate culture and informal structures, and systems
      and processes that are unique to a company. The GE executives' performance as
      CEOs depended on whether their new organizations were able to leverage each type
      of skill. The authors'findings challenge the conventional wisdom on human
      capital, which holds that there are two types of skill: general management, which
      is readily transferable, and company specific, which is not. In fact, they argue,
      other types of management capabilities can make a significant contribution to
      performance, and company-specific skills can be an asset in a new job.

PMID- 16649702
TI  - Mapping your innovation strategy.
AB  - In the complex sport of American football, teams rely on playbooks as thick as
      the Manhattan phone directory. But when it comes to creating innovative growth
      businesses-which is at least as complicated as professional football--most
      companies have not developed detailed game plans. Indeed, many managers have
      concluded that a fog enshrouds the world of innovation, obscuring high-potential
      opportunities. The authors believe that companies can penetrate that fog by
      developing growth strategies based on disruptive innovations, as defined by
      Clayton Christensen. Such innovations conform to a pattern: They offer an
      entirely new solution; they perform adequately along traditional dimensions and
      much better along other dimensions that matter more to target customers; and they
      are not initially appealing to powerful incumbents. Companies can develop
      customized checklists, or playbooks, by combining this basic pattern with
      analysis of major innovations in their markets. The key early on is to focus not
      on detailed financial estimates--which will always guide companies toward the
      markets most hostile to disruptive innovations--but on how well the innovation
      fits the pattern of success. It's also crucial to encourage flexibility:
      Companies must be willing to kill projects that are going nowhere, exempt
      innovations from standard development processes, and avoid burdening project
      teams with extra financing, which can keep them heading in the wrong direction.
      Companies can create competitive advantage by becoming champions at defining the
      pattern of successful innovations and executing against it. But as that pattern
      becomes obvious--and others emerge-building a sustainable advantage on innovation
      competencies will again prove elusive.

PMID- 16649703
TI  - The five messages leaders must manage.
AB  - If you want to know why so many organizations sink into chaos, look no further
      than their leaders' mouths. Over and over, leaders present grand, overarching-yet
      fuzzy-notions of where they think the company is going. They assume everyone
      shares their definitions of"vision;" "accountability," and "results". The result
      is often sloppy behavior and misalignment that can cost a company dearly.
      Effective communication is a leader's most critical tool for doing the essential
      job of leadership: inspiring the organization to take responsibility for creating
      a better future. Five topics wield extraordinary influence within a company:
      organizational structure and hierarchy, financial results, the leader's sense of
      his or her job, time management, and corporate culture. Properly defined,
      disseminated, and controlled, these topics give the leader opportunities for
      increased accountability and substantially better performance. For example, one
      CEO always keeps communications about hierarchy admirably brief and to the point.
      When he realized he needed to realign internal resources, he told the staff: "I'm
      changing the structure of resources so that we can execute more effectively."
      After unveiling a new organization chart, he said, "It's 10:45. You have until
      noon to be annoyed, should that be your reaction. At noon, pizza will be served.
      At one o'clock, we go to work in our new positions." The most effective leaders
      ask themselves, "What needs to happen today to get where we want to go? What
      vague belief or notion can I clarify or debunk?" A CEO who communicates precisely
      to ten direct reports, each of whom communicates with equal precision to 40 other
      employees, aligns the organization's commitment and energy with a well-understood
      vision of the firm's real goals and opportunities.

PMID- 16649704
TI  - Change management in government.
AB  - Since the days of John F. Kennedy's New Frontier, the American public's regard
      for the competence of public agencies and the value of the services they perform
      has steadily declined. During that time, innovations in management practice and
      thinking have mostly originated and been tested in the private sector. But recent
      events, such as the attacks on the World Trade Center and the engulfment of New
      Orleans, have demonstrated how essential it is for public agencies to be well
      run, too. Unfortunately, few public administrators have a background in change
      management, and a variety of factors-such as civil service rules, political
      considerations, and the limited tenures of agency heads-have combined to make
      true reform a rare event. These facts of public life may never go away. But some
      agency leaders have figured out how to court important stakeholders, rededicate
      staffers to an agency's true mission, undertake reform so comprehensively that
      resistant elements are unable to subvert it, and lay the groundwork for next
      steps clearly and systematically. Consultant Frank Ostroff has studied
      turnarounds at the federal Occupational Safety and Health Administration, the
      Government Accountability Office, and Special Operations Forces-the fast
      response, clandestine arm of the military. From these examples and others, he has
      distilled five principles that underlie successful change efforts: Improve
      performance against agency mission; win over external and internal stakeholders;
      establish a road map; recognize the connections among all the organizational
      elements; and be a leader, not a bureaucrat. Change programs that follow these
      principles are more likely to survive when leadership changes hands.

PMID- 16649705
TI  - Active construction of percepts about object location.
AB  - Mammals acquire much of their sensory information by actively moving their
      sensory organs. Rats, in particular, scan their surrounding environment with
      their whiskers. This form of active sensing induces specific patterns of temporal
      encoding of sensory information, which are based on a conversion of space into
      time via sensor movement. We investigate the ways in which object location is
      encoded by the whiskers and decoded by the brain. We recorded from first-order
      neurons located in the trigeminal ganglion (TG) of anaesthetized rats during
      epochs of artificial whisking induced by electrical stimulation of the facial
      motor nerve. We found that TG neurons encode the three positional coordinates
      with different codes. The horizontal coordinate (along the backward-forward axis)
      is encoded by two encoding schemes, both relying on the firing times of one type
      of TG neuron, the 'contact cell'. The radial coordinate (from face outward) is
      encoded primarily by the firing magnitude of another type of TG neurons, the
      'pressure cell'. The vertical coordinate (from ground up) is encoded by the
      identity of activated neurons. The decoding schemes of at least some of these
      sensory cues, our data suggest, are also active: cortical representations are
      generated by a thalamic comparison of cortical expectations with incoming sensory
      data.

PMID- 16649706
TI  - Neuronal encoding of natural stimuli: the rat tactile system.
AB  - A major challenge of sensory systems neuroscience is to quantify the brain
      activity underlying perceptual experiences and to explain this activity as the
      outcome of elemental neuronal response properties. One strategy is to measure
      variations in neuronal response in relation to controlled variations in an
      artificial stimulus. The limitation is that the stimuli scarcely resemble those
      which the sensory system has evolved to process-natural, behaviourally relevant
      stimuli. A more recent strategy is to measure neuronal responses during
      presentation of natural stimuli, but such experiments have failed to predict the
      observed responses according to the fundamental properties of neurons. In the
      work described here, we focus on tactile sensation in rats, and try to bridge the
      gap between neurons' responses to natural stimuli and their responses to
      controlled, artificial stimuli. We focus on texture, a submodality in which the
      rat whisker sensory system excels. Because the physical characteristics of
      texture stimuli have not yet been studied, the first set of experiments measures
      textures from the whiskers' point of view. The second set of experiments
      describes neurons' responses to textures. The third set of experiments computes
      kernels (estimates of the extracted stimulus features) of sensory neurons using
      white noise and then tries to account for natural texture responses according to
      these kernels. These investigations suggest ways of using natural stimuli to
      assemble a more complete picture of the neuronal basis of tactile sensation.

PMID- 16649707
TI  - Cortical commands in active touch.
AB  - The neocortex is an enormous network of extensively interconnected neurons. It
      has become clear that the computations performed by individual cortical neurons
      will critically depend on the quantitative composition of cortical activity. Here
      we discuss quantitative aspects of cortical activity and modes of cortical
      processing in the context of rodent active touch. Through in vivo whole-cell
      recordings one observes widespread subthreshold and very sparse evoked action
      potential (AP) activity in the somatosensory cortex both for passive whisker
      deflection in anaesthetized animals and during active whisker movements in awake
      animals. Neurons of the somatosensory cortex become either suppressed during
      whisking or activated by an efference copy of whisker movement signal that
      depolarize cells at certain phases of the whisking cycle. To probe the read out
      of cortical motor commands we applied intracellular stimulation in rat whisker
      motor cortex. We find that APs in individual cortical neurons can evoke long
      sequences of small whisker movements. The capacity of an individual neuron to
      evoke movements is most astonishing given the large number of neurons in whisker
      motor cortex. Thus, few cortical APs may suffice to control motor behaviour and
      such APs can be translated into action with the utmost precision. We conclude
      that there is very widespread subthreshold cortical activity and very sparse,
      highly specific cortical AP activity.

PMID- 16649708
TI  - Switching of sensorimotor transformations: antisaccades and parietal cortex.
AB  - The sensorimotor processing necessary in complex realistic situations goes beyond
      straight-forward application of a given sensorimotor transformation. Contextual
      information may make it necessary to switch to another sensorimotor
      transformation. We studied the issue of switching by using the mixed memory
      prosaccade/antisaccade task. Neurons of the lateral intra-parietal area (LIP)
      might be involved in computing the sensorimotor transformations for both
      prosaccades and antisaccades. LIP neurons may also be involved in switching to
      the antisaccade sensorimotor transformation, when an antisaccade is requested.
      Some neurons in LIP show a paradoxical pattern of activity-motor in space but
      visual in time. Funahashi, Chafee and Goldman-Rakic reported in 1993 a
      complimentary pattern of activity in prefrontal cortex-visual in space but motor
      in time. These odd observations are explained by the hypothesis that (1) the
      parietal cortex contains a sensorimotor transformation module, and prefrontal
      cortex a context categorization module, and (2) following target onset,
      information flows from early visual system to parietal cortex and on to
      prefrontal cortex; then, a second wave of activation, contingent on a switching
      signal, arrives back at parietal cortex. The duration of this loop is less than
      100 ms. Thus, the paradoxical activities are intermediate representations derived
      in the cognitive processing involved in switching sensorimotor transformations.

PMID- 16649709
TI  - Saccade initiation and the reliability of motor signals involved in the
      generation of saccadic eye movements.
AB  - We examined the trial-by-trial relationship between the metrics of saccadic eye
      movements and the activity of individual putative premotor neurons in the
      paramedian pontine reticular formation (PPRF) of rhesus monkeys. The region of
      the pons containing these excitatory burst neurons (EBNs) extends for several
      millimetres. Motoneurons innervating extraocular muscles integrate the output of
      hundreds or even thousands of these neurons. Accordingly, there was no reason to
      expect that relatively small variations in the activity of a single pontine
      neuron would be related to variations in saccade amplitude or speed observed
      during repetitive eye movements to the same target. Nonetheless, we observed
      consistent relationships between variations in the number of spikes in the burst
      of pontine neurons and the amplitude of the saccade. Trial-to-trial variations in
      the instantaneous spike frequency during a burst are associated with variations
      in the velocity profile of the movement. Based on these data, we conclude that
      the activity of pontine burst neurons is not statistically independent and that
      simultaneous recordings from multiple cells will reveal a high degree of
      correlated activity.

PMID- 16649710
TI  - Multiple roles of experience in decoding the neural representation of sensory
      stimuli.
AB  - Experience and perception are deeply intertwined. Experience, particularly early
      in life, shapes how sensory information is represented in the brain. Experience
      also establishes associations and can affect how sensory information guides
      behaviour. Central to these kinds of perceptual abilities are neural mechanisms
      that interpret, or decode, the brain's sensory representation, but little is
      known about how these decoding mechanisms depend on experience. Here I discuss
      several critical roles that experience might play in shaping these mechanisms.
      First, experience is likely to drive changes in neural connectivity to select the
      spatially and temporally distributed sensory signals that provide relevant
      information about a stimulus. Second, even the most relevant sensory signals
      provide incomplete information about the presence of a stimulus; also necessary
      is knowledge of the a priori probability of the stimulus, which must be learned
      from experience. Third, decoding noisy information is necessarily imperfect and
      therefore involves trade-offs like speed versus accuracy and false alarms versus
      misses. Experience is likely to provide ongoing feedback about the value of these
      trade-offs so that they might be adjusted appropriately. Each of these mechanisms
      appear to be capable of causing dramatic changes in sensitivity, response bias,
      response times and other manifestations of perceptual ability.

PMID- 16649711
TI  - Computational approaches to visual decision making.
AB  - Computational models based on diffusion processes have been proposed to account
      for human decision making behaviour in a variety of tasks. This study explores
      whether such models account for the speed and accuracy of perceptual decisions in
      a reaction-time random dot motion direction-discrimination task and whether they
      explain the decision-related activity of neurons recorded from the parietal
      cortex (area LIP) of monkeys performing the task. While a relatively simple
      diffusion model can explain the psychometric function and the mean response
      times, it fails to account for the response time distributions. By adding an
      'urgency mechanism' to the diffusion model the psychometric function, the mean
      response times, and the shape of the response time distributions can be
      explained. Such an urgency mechanism could be implemented in different ways, but
      the best match between the physiological data and model predictions is provided
      by a diffusion process with a time-variant gain of the sensory signals. It can be
      shown that such a time-variant decision process allows the monkey to perform
      optimally (in the sense of maximizing reward rate) given the risk of aborting a
      trial by breaking fixation before a choice can be reported.

PMID- 16649712
TI  - The inferior parietal lobule: where action becomes perception.
AB  - The view defended in this article is that action and perception share the same
      neural substrate. To substantiate this view, the anatomical and functional
      organization of the inferior parietal lobule (IPL) is reviewed. In particular, it
      will be shown that many IPL neurons discharge selectively when the monkey
      executes a given motor act (e.g. grasping). Most interestingly, most of them fire
      only if the coded motor act is followed by a subsequent specific motor act (e.g.
      placing). Some of these action-constrained motor neurons have mirror properties
      and selectively discharge during the observation of motor acts when these are
      embedded in a given action (e.g. grasping for eating, but not grasping for
      placing). Thus, the activation of these IPL neurons allows the observer not only
      to recognize the observed motor act, but also to predict what will be the next
      motor act of the action, that is to understand the intentions of the action's
      agent. The finding that the same neurons that are active during the execution of
      specific motor acts also mediate the understanding of the 'what' and the 'why' of
      others' actions provides strong evidence for a common neural substrate for action
      and perception.

PMID- 16649713
TI  - The evolution of the neocortex in mammals: intrinsic and extrinsic contributions
      to the cortical phenotype.
AB  - The neocortex is that portion of the brain that is involved in volitional motor
      control, perception, cognition and a number of other complex behaviours exhibited
      by mammals, including humans. Indeed, the increase in the size of the cortical
      sheet and cortical field number is one of the hallmarks of human brain evolution.
      Fossil records and comparative studies of the neocortex indicate that early
      mammalian neocortices were composed of only a few parts or cortical fields, and
      that in some lineages such as primates, the neocortex expanded dramatically. More
      significantly, the number of cortical fields increased and the connectivity
      between cortical fields became more complex. While we do not know the exact
      transformation between this type of increase in cortical field number and
      connectivity; and the emergence of complex behaviours like those mentioned above,
      we know that species that have large neocorticies with multiple parts generally
      have more complex behaviours, both overt and covert. Although a number of inroads
      have been made into understanding how neurons in the neocortex respond to a
      variety of stimuli, the micro and macro circuitry of particular neocortical
      fields, and the molecular developmental events that construct current
      organization, very little is known about how more cortical fields are added in
      evolution. In particular, we do not know the rules of change, nor the constraints
      imposed on evolving nervous systems that dictate the particular phenotype that
      will ultimately emerge. One reason why these issues are unresolved is that the
      brain is a compromise between existing genetic constraints and the need to adapt.
      Thus, the functions that the brain generates are absolutely imperfect, although
      functionally optimized. This makes it very difficult to determine the rules of
      construction, to generate viable computational models of brain evolution, and to
      predict the direction of changes that may occur over time. Despite these
      obstacles, it is still possible to study the evolution of the neocortex. One way
      is to study the products of the evolutionary process--extant mammal brains-and to
      make inferences about the process. The second way to study brain evolution is to
      examine the developmental mechanisms that give rise to complex brains. We have
      begun to test our theories regarding cortical evolution, generated from
      comparative studies, by 'tweaking' in a developing nervous system what we believe
      is naturally being modified in evolution. Our goals are to identify the
      constraints imposed on the evolving neocortex, to disentangle the genetic and
      activity dependent mechanisms that give rise to complex brains, and ultimately to
      produce a cortical phenotype that is consistent with what would naturally occur
      in evolution.

PMID- 16649714
TI  - Decoding the temporal evolution of a simple perceptual act.
AB  - Most perceptual tasks require sequential steps to be carried out. This must be
      the case, for example, when subjects discriminate the difference in frequency
      between two mechanical vibrations applied sequentially to their fingertips. This
      perceptual task can be understood as a chain of neural operations: encoding the
      two consecutive stimulus frequencies, maintaining the first stimulus in working
      memory, comparing the second stimulus to the memory trace left by the first
      stimulus, and communicating the result of the comparison to the motor apparatus.
      Where and how in the brain are these cognitive operations executed? We addressed
      this problem by recording single neurons from several cortical areas while
      trained monkeys executed the vibrotactile discrimination task. We found that
      primary somatosensory cortex (S1) drives higher cortical areas where past and
      current sensory information are combined, such that a comparison of the two
      evolves into a decision. Consistent with this result, direct activation of the S1
      can trigger quantifiable percepts in this task. These findings provide a fairly
      complete panorama of the neural dynamics that underlies the transformation of
      sensory information into an action and emphasize the importance of studying
      multiple cortical areas during the same behavioural task.

PMID- 16649715
TI  - Probabilistic mechanisms in sensorimotor control.
AB  - Uncertainty constitutes a fundamental constraint on human sensorimotor control.
      Our sensors are noisy and do not provide perfect information about all the
      properties of the world. Moreover, our muscles generate noisy outputs and many
      tasks we perform vary in an unpredictable way. Here we review the computations
      that the CNS uses in the face of such sensory, motor and task uncertainty. We
      show that the CNS reduces the uncertainty in estimates about the state of the
      world by using a Bayesian combination of prior knowledge and sensory feedback. It
      is shown that these mechanisms generalize to state estimation of ones own body
      during movement. We review how the CNS optimizes decisions based on these
      estimates, examining the error criterion that people optimize when performing
      targeted movements. Finally, we describe how signal-dependent noise on the motor
      output places constraints on performance. Goal-directed movement arises from a
      model in which the statistics of our actions are optimized. Together these
      studies provide a probabilistic framework for sensorimotor control.

PMID- 16649716
TI  - Human brain activation during viewing of dynamic natural scenes.
AB  - To what extent do brains of different human individuals operate in a similar
      manner? Here we explored the organization and function of different brain regions
      under progressively more natural conditions. Applying an unbiased analysis, in
      which spatiotemporal activity patterns in one brain were used to 'model' activity
      in another brain, we found a striking level of voxel by voxel synchronization
      between individuals during free viewing of an audio-visual movie. This
      intersubject correlation was evident not only in primary and secondary visual and
      auditory areas, but also in association cortices. The results reveal a surprising
      tendency of individual brains to 'tick collectively' during natural vision.
      Moreover, our results demonstrate that the unitary nature of conscious experience
      in fact consists of temporally interleaved and highly selective activations in an
      ensemble of specialized regions, each of which 'picks-up' and analyses its own
      unique subset of stimuli according to its functional specialization. Applying
      reverse correlation to the movie stimuli provides a powerful methodology for
      revealing both known and unexpected functional specializations in those cortical
      areas activated by the movie.

PMID- 16649717
TI  - Representation of object images by combinations of visual features in the macaque
      inferior temporal cortex.
AB  - The ventral visual pathway is essential for object recognition where features
      necessary for recognition are extracted from object images. This pathway is not
      directly related to action; nevertheless extraction of features from object
      images through this pathway is closely related to actions since we determine our
      behaviour based on sensory information, such as object images in the scene. To
      link perception and action, we have investigated neural representation of object
      images in area TE. Area TE, the anterior part of the inferior temporal (IT)
      cortex, is the final purely visual area in the ventral visual pathway. Since
      individual neurons in this area respond to features less complex than object
      images, an object image is supposed to be represented by multiple features. Here,
      to investigate sets of features necessary for representation of object images, we
      conducted a combination study of an optical imaging technique and single cellular
      recordings from anesthetized macaque monkeys.

PMID- 16649718
TI  - Psychophysical investigations into cortical encoding of vibrotactile stimuli.
AB  - Neurons in primary somatosensory cortex (S1) respond to vibrotactile stimuli by
      firing in phase with each cycle of the vibration. We have investigated how neural
      activity in S1 might contribute to people's perception of vibration frequency.
      The contribution of S1 was confirmed using transcranial magnetic stimulation
      (TMS): accuracy in comparing the frequency of two sequential vibrations was
      reduced by a single TMS pulse delivered to S1 in the interval between the two
      vibrations. More recent experiments have revealed that participants use the
      velocity (or energy) of the stimulus when judging its frequency. This is
      consistent with a contribution from S1: electrophysiological recording in S1
      cortex of rats shows that neurons in S1 do not explicitly code vibration
      frequency, but instead code the product of frequency and amplitude (proportional
      to the mean velocity or energy of the vibration). Further, frequency
      discrimination is reduced by the addition of even very small amounts of noise to
      the temporal structure of the vibrations (making them irregular). However, noise
      has no effect if the two vibrations are presented on opposite fingertips (i.e.
      beyond the range of receptive field sizes of neurons in S1), or if there is no
      difference in their velocity. Therefore, when judging vibration frequency, humans
      utilize information about stimulus velocity as coded by neurons in S1, but this
      coding is dependent on the temporally regular input of the vibration.

PMID- 16649719
TI  - Why is language unique to humans?
AB  - Cognitive neuroscience has focused on language acquisition as one of the main
      domains to test the respective roles of statistical vs. rule-like computation.
      Recent studies have uncovered that the brain of human neconates displays a
      typical signature in response to speech sounds even a few hours after birth. This
      suggests that neuroscience and linguistics converge on the view that, to a large
      extent, language acquisition arises due to our genetic endowment. Our research
      has also shown how statistical dependencies and the ability to draw structural
      generalizations are basic processes that interact intimately. First, we explore
      how the rhythmic properties of language bias word segmentation. Second, we
      demonstrate that natural speech categories play specific roles during language
      acquisition: some categories are optimally suited to compute statistical
      dependencies while other categories are optimally suited for the extraction of
      structural generalizations.

PMID- 16649720
TI  - Quadriscupid aortic valve: a rare entity.

PMID- 16649721
TI  - Inhibition of sodium-dependent calcium overload to treat myocardial ischemia.
AB  - Because intracellular sodium and calcium overload play a key role in both
      mechanical and electrical dysfunction during myocardial ischemia, inhibition of
      the late sodium current would be expected to decrease the intracellular sodium
      and calcium overloads and thereby reduce their undesirable effects. Ranolazine
      selectively inhibits late sodium current relative to peak sodium current, and
      attenuates the abnormalities of ventricular repolarization and contractility
      associated with ischemia. This is the currently proposed mechanism (hypothesis)
      of action of the effects of ranolazine during myocardial ischemia.

PMID- 16649722
TI  - Aspirin resistance, an emerging, often overlooked, factor in the management of
      patients with coronary artery disease.
AB  - Aspirin is the most widely used medication in patients with cardiovascular
      disease. It has had a greater effect on patients with cardiovascular disease than
      any other drug. With the importance of aspirin now known for decades, it is
      recently becoming clearer that some patients do not derive as great a benefit
      from this "wonder drug" secondary to their resistance to its effects. Aspirin
      resistance, its prevalence, its identification, and how to overcome or avert it
      with other medications then becomes a central topic of discussion as important,
      if not more so, than the importance of aspirin itself as a cornerstone in the
      treatment of patients with cardiovascular disease. This review explores the
      current understanding of the mechanism of aspirin resistance with regard to its
      prevalence and the magnitude of its clinical significance. It also examines the
      therapeutic implications of a diagnosis of aspirin resistance.

PMID- 16649723
TI  - Use and side-effect profile of spironolactone in a private cardiologist's
      practice.
AB  - BACKGROUND: The beneficial effects of spironolactone on the treatment of
      cardiovascular diseases are well known, but translating these benefits into
      private practice can be difficult because of the drug's side-effect profile.
      HYPOTHESIS: When patients are monitored over the long term, spironolactone can be
      used safely with an acceptable side-effect profile. METHODS: We retrospectively
      studied 762 patients taking spironolactone over a 7-year period in a
      cardiologist's referral-based practice and monitored them for side effects from
      the medication. RESULTS: Data were available on 762 patients. The average age of
      our patients when started on the medication was 67.2 +/- 0.5 years. Of these, 585
      (76.8%) patients were treated for heart failure and 155 (20.3%) for hypertension.
      An average dose of 38.4 +/- 1.4 mg of spironolactone was used for treatment of
      all conditions. Of the 762 patients, 81 (10.6%) experienced side effects while
      using the medication; 40 had hyperkalemia (5.3%), 14 had gynecomastia (1.8%), and
      15 had gastritis (2%). Of the patients with hyperkalemia, average creatinine
      clearance decreased from 64.6 +/- 5.8 ml/min at therapy start to 50.3 +/- 5.5
      ml/min at the time of onset of side effects. CONCLUSION: Spironolactone can be
      used with an acceptable side-effect profile as long as patients are monitored
      long-term while receiving the medication.

PMID- 16649724
TI  - Amount of left ventricular hypertrophy determines the plasma N-terminal pro-brain
      natriuretic peptide level in patients with hypertrophic cardiomyopathy and normal
      left ventricular ejection fraction.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is increased in
      patients with hypertrophic cardiomyopathy (HCM); however, the determinants of NT
      proBNP level have not been clarified in HCM. HYPOTHESIS: This study was performed
      to determine the relationship between NT-proBNP levels and various
      echocardiographic variables of patients with HCM and normal left ventricular
      ejection fraction (LVEF). METHODS: We assessed plasma NT-proBNP levels and
      echocardiographic variables of 36 patients (19 men, 58 +/- 14 years) with HCM and
      an LVEF of > or = 55%. Echocardiographic variables measured were LV wall
      thickness, end-diastolic LV internal dimension (LVIDd) and volume (LVEDV), LV
      mass, and LV mass index (LV mass/body surface area, LVMI). Left ventricular
      outflow tract pressure gradient, transmitral E and A velocities, deceleration
      time (DT) of the transmitral E wave, and septal annular E' velocity were measured
      by Doppler technique. The relationship between echocardiographic variables and
      plasma NT-proBNP level was analyzed. RESULTS: The plasma NT-proBNP level was
      775.2 +/- 994.2 pg/ml (range 33.1-4729.0 pg/ml). It showed positive correlations
      with LV end-diastolic septal thickness (r = 0.39, p = 0.010) and LVMI (r = 0.27,
      p = 0.050), while it revealed negative correlations with LVIDd (r = -0.44, p =
      0.004), LVEDV (r = -0.44, p = 0.004) and DT(r = -0.31,p = 0.034). The NT-proBNP
      level was higher in the patients with than in those without LV diastolic
      dysfunction (p = 0.033) and was independently related to LVIDd (p = 0.001), LVMI
      (p = 0.006) and DT (p = 0.031) by multivariate analysis. CONCLUSION: In patients
      with HCM and normal LVEF, the amount of LV hypertrophy and LV diastolic
      dysfunction may exert a significant role in determining plasma NT-proBNP level.

PMID- 16649725
TI  - The cardiovascular patient's perceptions of complementary and alternative
      medicine.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use is common among
      patients with cardiovascular disorders and is generally underrecognized by
      physicians. The attitudes of these patients regarding these therapies and their
      perceptions of safety and efficacy have not been well defined. METHODS: A written
      survey was received from a cohort of outpatients seen at a large outpatient
      cardiovascular clinic in Texas. Over 75% of patients responded, with more than
      90% of returned surveys adequate for analysis. RESULTS: Of the 210 respondents
      113 admitted to CAM use, with Vitamins E and C being the most frequently utilized
      agents. Women were significantly more likely to take CAM than men (69 vs. 46%, p
      = 0.002), particularly those taking hormone replacement therapy. Over half of
      patients surveyed stated their cardiologist was unaware of their use of CAM. Only
      15% of patients felt that CAM was more efficacious than their traditional
      medications, but almost half felt it was significantly safer. A similar number
      were unaware of any interactions between CAM and their other medications.
      CONCLUSIONS: Use of CAM is common in cardiology outpatients, and many patients
      remain unaware of potential health risks. Physicians should routinely question
      patients about use of CAM and attempt to educate users regarding potential health
      risks.

PMID- 16649726
TI  - Assessment of markers of thrombin generation in patients with acute myocardial
      infarction complicated by ventricular fibrillation.
AB  - BACKGROUND: In most cases, sudden cardiac death is triggered by ischemia-related
      ventricular tachyarrhythmias and accounts for 50% of deaths from cardiovascular
      disease in developed countries. Chronic elevation of indicators of coagulation
      activation has been found in patients with coronary heart disease, but a role of
      coagulation activation as a potential risk factor for ventricular fibrillation
      (VF) during acute myocardial infarction (MI) has not been investigated. METHODS:
      We enrolled 50 patients with a history of MI, of whom 26 presented with VF in the
      acute phase of myocardial ischemia; 24 patients had an acute MI without
      ventricular tachyarrhythmias. Levels of thrombin-antithrombin complexes (TAT),
      prothrombin fragment F1 + 2 (F1 + 2), fibrinopeptide A (FPA), plasmin-antiplasmin
      complexes (PAP), protein C, antithrombin, activated partial thromboplastin time
      (aPTT), thromboplastin time, D-Dimer, fibrinogen, and high-sensitivity C-reactive
      protein (hs-CRP) were measured in plasma samples of all patients. Blood
      collection was obtained sequentially in two separate settings. Patients were
      studied at a median of 351 days after the acute coronary event. RESULTS: Higher
      levels of TAT complexes (13.4 +/- 22.2 vs. 3.03 +/- 4.3 microg/l; p = 0.02), FPA
      (79.7 +/- 132.3 vs. 24.04 +/- 41.3 ng/ml; p = 0.04), and F1+2 (1.89 +/- 1.3 vs.
      1.16 +/- 0.5 nmol/l; p = 0.01) were observed in patients with VF compared with
      patients without ventricular tachyarrhythmias during the acute phase of MI. D
      Dimer levels displayed a trend without reaching statistical significance (0.69 +/
      0.48 vs. 0.48 +/- 0.24 mg/l; p = 0.06). No differences were found in hs-CRP
      (3.25 +/- 4.5 vs. 4.4 +/- 8.8 mg/l; p = 0.5) and fibrinogen (2.8 +/- 0.9 vs. 2.7
      +/- 0.9 g/l; p = 0.6) measurements. Repeat assessment of markers of coagulation
      activation at a median of 847 days revealed a highly significant decrease in
      patients with VF. CONCLUSIONS: Markers of thrombin generation are transiently
      increased in patients with VF during the acute phase of MI. These findings have
      implications for risk assessment and genetic screening of patients prone to VF
      during acute myocardial ischemia.

PMID- 16649727
TI  - Depression and thyroid axis function in coronary artery disease: impact of
      cardiac impairment and gender.
AB  - BACKGROUND: Increased rates of depression are reported in coronary artery disease
      (CAD). In heart disease, depression increases disability, reduces quality of
      life, and increases mortality. HYPOTHESIS: The study was undertaken to examine
      the relationship between depression and thyroid axis function in patients with
      CAD. METHODS: In all, 73 patients with CAD, consecutively admitted to a cardiac
      rehabilitation hospital, were assessed for depression using the Hospital Anxiety
      and Depression scale (HADS). Blood was drawn for assessment of thyroid axis
      hormones and the N-amino terminal fragment of the pro-B-type natriuretic peptide
      (NT-pro BNP). RESULTS: The patients with CAD with depressive symptoms had a
      higher prevalence of cardiac failure (p = 0.04), higher NT-pro BNP concentrations
      (p = 0.02), and lower free triiodothyronine (T3) concentrations (p = 0.04) than
      patients with CAD but without depressive symptoms. They also showed a strong
      trend (p = 0.058) toward a higher incidence of the low T3 syndrome. Higher NT-pro
      BNP concentrations were related to lower total T3 concentrations (r = -0.294, p =
      0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002). In men,
      higher scores of depression were related to lower total T3 concentration (r = 
      0.289, p = 0.034) and to higher NT-pro BNP concentration (r = 0.380, p = 0.005).
      CONCLUSION: These findings suggest that symptoms of depression in patients with
      CAD are associated with changes in thyroid axis function and with cardiac
      impairment, especially in men.

PMID- 16649728
TI  - Postpartum dissection of the left main coronary artery.
AB  - Peripartum coronary artery dissection is rare, but it is an increasingly
      recognized risk to women of childbearing age. Literature reviews reveal that
      about 80% of the population with spontaneous coronary artery dissections (SCAD)
      are female, and approximately 25-33% of cases occurred while the woman was
      pregnant or in the peripartum phase. Most cases have presented within 2 weeks of
      delivery. The left anterior descending is the most commonly affected vessel. The
      etiology is poorly understood, but many reports suggest that SCAD occurs as a
      result of protease release secondary to an eosinophilic vasculitis resulting in
      vessel lysis. Many investigators have examined the correlation between peripartum
      SCAD and estrogen levels; however, case studies have shown conflicting results
      regarding estrogen levels as the putative causative factor. Optimal treatment
      remains controversial. Presently, stenting appears to be best employed in the
      patients who have single-vessel dissection not involving the left main coronary
      artery (LMCA). Surgical revascularization via coronary artery bypass graft
      remains the optimal therapy in patients whose dissection involves the LMCA, in
      patients with concurrent multivessel dissection, and in patients with disease
      refractory to medical management. It is important to consider coronary artery
      dissection in the differential of any young woman who presents with signs or
      symptoms consistent with acute coronary syndrome, particularly if she is
      peripartum. Furthermore, once suspected, it is imperative that a definitive
      diagnostic study, that is, coronary angiography, be completed prior to the
      initiation of treatment whenever possible.

PMID- 16649729
TI  - Images in cardiology: giant left atrium.

PMID- 16649730
TI  - Images in cardiology: giant left main coronary artery aneurysm with organized
      thrombus.

PMID- 16649731
TI  - Ernest Henry Starling.

PMID- 16649732
TI  - Stem cell medicine--2006.

PMID- 16649733
TI  - Quality of life in Parkinson's disease--Indian scenario.
AB  - The subjective sense of well being is central to the concept of quality of life
      (QoL) and a good QoL should be the ultimate goal to any therapeutic measure. In
      Parkinson's disease (PD), several rating scale are in vogue to measure the QoL,
      namely PDQ-39, PDQ-8, SF-36, Likert scale etc. Parkinson's Impact Scale (PIMS)
      has been used in this study to assess the QoL which includes 10 items.
      METHODOLOGY: Thirty two patients of Parkinson's disease satisfying the UK
      Parkinson's disease brain bank diagnostic criteria, ranging from HY stage I to IV
      have been recruited. UPDRS was also administered to them. Statistical analysis
      was performed using Spearman rank correlation and multivariate stepwise
      regression analysis using SPSS for windows. RESULT: Seventy two percents were
      male, all getting levodopa, 72% got anticholinergics. Monthly income varied from
      Rs.800 (US dollars 17.10) to Rs.15,000 (US dollars 320) pm. Eighty eight percent
      belonged to HY II-III. UPDRS score ranged from 3-85 (40.4 +/- 18.6). PIMS total
      score ranged from 1-22 (10.4 +/- 6.1). DISCUSSION AND CONSLUSION: The QoL
      deteriorates with H-Y staging, the UPDRS score, not with advancing age as seen in
      other studies. It is also significantly influenced by duration of the disease and
      financial security. Surprisingly, the family and community relations were not
      significantly affected with advancing disease, perhaps due the close family and
      social tie up among Indians. So, measurement of QoL should be made an essential
      part to the routine assessment of PD patients to get a complete scenario of the
      problem. PIMS can serve as a comprehensive tool for the same suitable for use in
      the OPD.

PMID- 16649734
TI  - Sodium and potassium excretion in normotensive and hypertensive population in
      Kashmir.
AB  - One hundred thirty five hypertensive patients and equal number of age and sex
      matched healthy controls were taken up for studying the relationship of 24 hour
      urinary sodium and potassium excretion, sodium-potassium molar ratio and body
      mass index (BMI) with blood pressure in normotensive and hypertensive population
      in Kashmir. There was statistically significant elevated 24 hour urinary sodium
      excretion (p < .001), increased Na+-K+ molar ratio, significantly higher BMI in
      hypertensive population as compared to controls whereas there was a lower 24 hour
      urinary excretion of potassium (p > .20) in patients with hypertension. Thus
      sodium and potassium excretion, Na+-K+ molar ratio and body mass index has direct
      bearing in perpetuation or causation of hypertension in Kashmir which may be
      related to intake of salt tea.

PMID- 16649735
TI  - Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies:
      Tata Memorial experience.
AB  - Rituximab has been used extensively in lymphoproliferative disorders. We
      evaluated the results of 64 consecutive patients treated between 2001 and 2004 at
      our institution. This included 54 males and 10 females. The median age was 54
      years (range 17 to 85 years). One-fourth of patients were above 60 years. The
      histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed
      as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one
      were in advanced stage (III/IV) of disease. B symptoms were present in 47% of
      cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab
      monotherapy was used in 17 cases. Rituximab was used in combination with
      chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in
      one, hypotension in one and minor infusional reactions in four others. The
      patient who developed anaphylaxis required discontinuation of further Rituximab.
      Growth factors were used in 25 patients. Febrile neutropenia occurred in 19
      patients. The overall RR (CR + PR) was 72%. One patient had stable disease and
      progressive disease was documented in 17 patients. A total of seven patients
      died, three due to progressive disease, three due to chemotherapy related
      toxicity and one due to an unrelated cause. We conclude that Rituximab is a
      valuable addition to the treatment armamentarium of lymphoproliferative
      disorders.

PMID- 16649736
TI  - Chemical shift imaging in diagnosis of adrenal adenoma.

PMID- 16649737
TI  - Spontaneous migration of central venous catheter tip.

PMID- 16649738
TI  - Comprehensive stroke care: an overview.
AB  - Stroke is a global epidemic and an important cause of morbidity and mortality. It
      ranks next to cardiovascular disease and cancer as a cause of death. "India is
      likely to suffer huge social and economic burden in the rehabilitation of stroke
      patients owing to increased life expectancy" and urbanization. Though, there are
      national programs in malaria eradication and tuberculosis control, there is
      hardly any governmental support in stroke management and rehabilitation. We
      propose to formulate stroke-prevention strategies specific to our national needs
      and covering all the age groups. Allocation of resources towards the stroke
      management and research is needed. Emphasis on stroke awareness in community
      should be stressed and should be inclusive of means of primordial and primary
      prevention apart from management of stroke and its recurrence. Recent
      international experience in stroke management has suggested the need of
      specialized stroke units (comprehensive stroke care under one roof). We wish to
      establish the need of creating awareness regarding the urgency of specialized
      care in acute stroke. We also wish to motivate our national health institutions
      to offer affordable, evidence based management of stroke and offer opportunities
      in stroke training and research.

PMID- 16649739
TI  - Subarachnoid haemorrhage as a presentation of cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis can present with a variety of clinical symptoms
      ranging from isolated headache to deep coma. Subarachnoid haemorrhage is a rare
      presentation. In the report, we describe a case of non-puerperal venous
      thrombosis of many dural sinuses manifesting on imaging solely as localized
      subarachnoid haemorrhage without underlying parenchymal involvement.

PMID- 16649740
TI  - Partial HPRT deficiency (Kelley-Seegmiller syndrome).
AB  - Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency is an X-linked
      defect of purine metabolism. Clinical manifestations are usually related to the
      degree of enzyme deficiency; complete HPRT deficiency (Lesh-Nyhan Syndrome)
      presenting with severe neurological or renal symptoms, or partial HPRT deficiency
      (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. We
      report a case of partial HPRT deficiency presenting as chronic tophaceous gout,
      mental retardation, nephrolithiasis and family history suggestive of X-linked
      inheritance, for its rarity.

PMID- 16649741
TI  - Thallium poisoning presenting as paresthesias, paresis, psychosis and pain in
      abdomen.
AB  - Due to involvement of multiple systems, thallium poisoning is notorious for
      complexity and seriousness as symptoms of toxicity are non-specific and diverse.
      Alopecia and painful neuropathy are its cardinal features, others being
      gastrointestinal disturbances, encephalopathy, tachycardia, ataxia, hepatorenal
      and cardiac damage etc. We report a case of thallium poisoning who presented
      initially with gastrointestinal symptoms and later developed neurological
      features (peripheral neuropathy and delirium). Various diagnoses were entertained
      in this case and thallium poisoning was suspected only after he developed
      alopecia and neuropsychosis. He made a significant recovery by conservative
      management in spite of delay in diagnosis. We conclude that a high level of
      suspicion should be kept for thallium poisoning, especially in patients with
      painful, peripheral neuropathy and gastrointestinal symptoms which appear earlier
      than alopecia, since prognosis is more rewarding with early diagnosis, leading to
      complete recovery.

PMID- 16649742
TI  - API consensus guidelines for use of antiretroviral therapy in adults (API-ART
      guidelines). Endorsed by the AIDS Society of India.
AB  - With rational use of antiretroviral therapy (ART), human immunodeficiency virus
      (HIV) infection has been transformed into a chronic manageable illness like
      diabetes and hypertension. These guidelines provide information on state of art,
      evidence based approach for use of ART in Indian context. When to initiate ART?
      Antiretroviral therapy is indicated for all symptomatic HIV infected persons
      regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic
      patients, ART should be offered when the CD4 counts < 200/mm3 and should be
      considered in patients with CD4 counts between 200-250/mm3. Therapy is not
      recommended for patients with CD4 count more than 350/ mm3. Involvement of
      patient in all treatment decisions and assessing readiness is critical before
      initiating ART. What to start with? A non-nucleoside reverse transcriptase
      inhibitor (NNRTI) based regimen is recommended for antiretroviral naive patients.
      The choice between nevirapine and efavirenz is based on differences in adverse
      events profiles; cost and availability of convenient fixed dose combinations and
      need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse
      transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations
      and ART strategies not to be used in clinical practice has been enlisted. How to
      follow up? Recommendations have been made for baseline evaluation and monitoring
      of patients on ART. These include guidelines on laboratory and clinical
      evaluation. A plasma viral load at 6 months after initiation of first-line ART is
      strongly recommended. Yearly estimation of lipid profile has been recommended.
      How to identify and manage ART failure? The guidelines recognize the issue of
      identifying ART failure late if only CD4 counts are used for monitoring. In the
      absence of resistance testing various second-line regimens have been enlisted. A
      boosted protease inhibitor based regimen is recommended in this situation to be
      combined with 2-NRTIs. Special situations Recommendations have been made for use
      of ART in HIV-TB, HIV-HBV, and HIV-HCV co-infected patients. In patients with
      active TB and a CD4 count < 200/mm3, initiation of ART is recommended as soon as
      the anti-TB treatment is tolerated. Efavirenz is the only ARV drug, which can be
      safely used with rifampicin. In pregnancy use of single dose nevirapine for
      reducing risk of mother to child transmission of HIV is not recommended, because
      of the risk of development of resistance. For post-exposure prophylaxis taking
      ART treatment history of the source patient is crucial in designing an effective
      regimen.

PMID- 16649743
TI  - Electricity & the heart--philatelic sequelae.

PMID- 16649744
TI  - Is the presence or absence of Helicobacter pylori in gastric mucosa a greater
      risk.

PMID- 16649745
TI  - Chlamydia pneumoniae--seroprevalance among adults presenting with acute community
      acquired pneumonia (CAP).

PMID- 16649746
TI  - Time to thrombolysis in patients with acute myocardial infarction in a tertiary
      referral centre: an important performance indicator in an emergency department.

PMID- 16649747
TI  - Dewetting instability during the formation of polymersomes from block-copolymer
      stabilized double emulsions.
AB  - We investigate the formation of polymer vesicles, or polymersomes, of polystyrene
      block-poly(ethylene oxide) diblock copolymers using double emulsion droplets of
      controlled architecture as templates. To engineer the structure of the
      polymersomes, it is important to consider the concentration of diblock copolymer
      in the middle phase of the double emulsion. We describe how the presence of
      excess polymer can induce a transition from complete wetting to partial wetting
      of the middle phase, resulting in polymer shells with inhomogeneous thicknesses.

PMID- 16649748
TI  - Nanoscale conductivity mapping of hybrid nanoarchitectures: ultrathin poly(o
      phenylenediamine) on mesoporous manganese oxide ambigels.
AB  - We use conductive-probe atomic force microscopy (CP-AFM) to characterize and
      image hybrid electrode structures comprising mesoporous manganese oxide (MnO2)
      ambigel nanoarchitectures coated with an ultrathin (<10 nm) electrodeposited
      layer of poly(o-phenylenediamine), PPD. Native MnO2 ambigel films, supported on
      indium tin oxide (ITO) substrates, exhibit spatially uniform conductivity that
      correlates well with the topography of the MnO2 film, confirming that the
      nanoscopic oxide network is effectively wired to the underlying ITO substrate.
      Following the self-limiting electrodeposition of the PPD coating onto the high
      surface-area (>200 m2 g(-1)) MnO2 ambigel, the resulting hybrid structures
      display an approximately 20-fold reduction in conductivity, as determined from CP
      AFM measurements. The CP-AFM imaging studies confirm that the ultrathin,
      insulating PPD layer conformally and homogeneously coats the conductive
      nanoarchitecture. CP-AFM imaging of PPD-MnO2 hybrid electrodes following
      electrochemical cycling in an aqueous acid electrolyte reveals that the ultrathin
      PPD coating serves as an effective barrier to the electrolyte, protecting the
      underlying MnO2 nanoarchitecture from electrochemical dissolution.

PMID- 16649749
TI  - Photopatterned polymer brushes promoting cell adhesion gradients.
AB  - The ability to spatially control cellular adhesion in a continuous manner on a
      biocompatible substrate is an important factor in designing new biomaterials for
      use in wound healing and tissue engineering applications. In this work, a novel
      method of engineering cell-adhesive RGD-ligand density gradients to control
      specific cell adhesion across a substrate is presented. Polymer brushes
      exhibiting spatially defined gradients in chain density are created and
      subsequently functionalized with RGD to create ligand density gradients capable
      of inducing cell adhesion on an otherwise weakly adhesive substrate. Cell studies
      indicate that these ligand-functionalized surfaces are noncytotoxic, with
      cellular adhesion increasing with RGD-ligand density across the gradient brush
      surface.

PMID- 16649750
TI  - Preparation and characterization of terraced surfaces of low-index faces of
      anatase, rutile, and brookite.
AB  - Simple polishing and relatively low temperature annealing procedures for
      preparing atomically flat terraced surfaces of various single-crystal TiO2
      polymorphs are described. Anatase (101), anatase (001), rutile (100), rutile
      (110), and brookite (111) surfaces could all be prepared with a terraced surface
      structure as revealed in AFM images. The rutile (100) and (110) and anatase (101)
      surfaces were also shown to produce acceptable LEED patterns immediately upon
      insertion into a UHV system without the usual sputter and anneal cycles.

PMID- 16649751
TI  - Electric-field oriented polymer blend film for proton conduction.
AB  - A novel proton conductor has been realized by employing a ternary polymer blend
      system in combination with an electric-field orientation technique. A polymer
      film recast from a solution containing poly(acrylic acid), poly(vinyl butyral),
      and fluoroalkyl graft polymer under 2 kV.cm(-1) exhibited 10 times higher proton
      conductivity than that prepared without the external electric field. However,
      when the film was prepared under a field higher than 4 kV.cm(-1), proton
      conductivity decreased. The membranous character has been investigated by SEM and
      AFM observations. As a result, it has been proven that an electric-field
      treatment of 2 kV.cm(-1) forms the largest hydrophilic domains for proton
      conduction in the film. The alteration of the phase separation morphology induced
      by the electric field well explains the proton conductivity change.

PMID- 16649752
TI  - Evidence of a unique electron donor-acceptor property for platinum nanoparticles
      as studied by XPS.
AB  - In the interaction of PVP with Pt nanoparticles <7 nm in size, charge transfer is
      from carbonyl groups in PVP to Pt nanoparticles, whereas in the interaction of
      PVP with bulk Pt or Pt nanoparticles >25 nm in size, charge transfer is from Pt
      metal to the polymer side chain of PVP. There exists a critical nanoparticle size
      between 7 and 25 nm that would lead to a switch in the electron donor-acceptor
      property.

PMID- 16649753
TI  - Surface gradient material: from superhydrophobicity to superhydrophilicity.
AB  - We have developed a simple method to fabricate a gradient from
      superhydrophobicity to superhydrophilicity. It is based on the controlled self
      assembled monolayer consisting of a thiol molecule on a gold surface and the
      amplifying effect of the wetting property on a rough surface. Using a relatively
      dilute HS(CH2)11CH3 solution (0.05 mmol/L), we found that the density of
      molecules on the surface can be controlled by varying the immersion time. Slowly
      adding the dilute solution to the container holding the rough gold substrate will
      lead to a density gradient along the surface. After the complementary adsorption
      of HS(CH2)10CH2OH, the surface exhibits a gradient from superhydrophobicity to
      superhydrophilicity. The slope of the gradient can be conveniently tuned by
      varying the speed of addition. Cassie-Baxter and Wenzel equations are employed to
      explain this special property based on the rough structure and the molecular
      composition gradient that have been determined by XPS. This kind of material
      would provide a larger oriented driving force for many important biological and
      physical processes and might have potential applications in water droplet
      movement, oriented axonal specification of neurons, protein adhesion, and so on.

PMID- 16649754
TI  - Solvent entrainment in and flocculation of asphaltenic aggregates probed by small
      angle neutron scattering.
AB  - While small-angle neutron scattering (SANS) has proven to be very useful for
      deducing the sizes and masses of asphaltenic aggregates in solution, care must be
      taken to account for solvation effects within the aggregates so as to not err in
      the characterization of these important systems. SANS measurements were performed
      on solutions of asphaltenes dispersed in deuterated solvents in which a broad
      spectrum of solute and solvent chemical compositions was represented. Fits to the
      scattering intensity curves were performed using the Guinier approximation, the
      Ornstein-Zernike (or Zimm) model, a mass-fractal model, and a polydisperse
      cylinder model. The mass-fractal model provided apparent fractal dimensions (2.2
      3) for the aggregates that generally decreased with increasing aggregate size,
      indicating increased surface roughness for larger aggregates. The polydisperse
      cylinder model provided typical values of the particle thicknesses from 5 to 32
      angstroms, the average particle radius from 25 to 125 angstroms, and
      approximately 30% radius polydispersity. Subsequent calculation of average
      aggregate molar masses suggested a range of solvent entrainment from 30 to 50%
      (v/v) within the aggregates that were consistent with previous viscosity
      measurements. Additional calculations were performed to estimate the proportion
      of microparticle to nanoparticle aggregates in the solutions. The results
      indicate that the inclusion of solvation effects is essential for the accurate
      determination of aggregate molecular weights and fractal dimensions.

PMID- 16649755
TI  - The application of 1H high-resolution magic-angle spinning NMR for the study of
      clay-organic associations in natural and synthetic complexes.
AB  - The preferential sorption of model compounds to calcium-exchanged montmorillonite
      surfaces was investigated using 1H high-resolution magic-angle spinning (HR-MAS)
      and liquid-state NMR. Synthetic mixtures, representing the major structural
      categories abundant in natural organic matter (NOM), and two soil extracts were
      sorbed to montmorillonite. The NMR spectra indicate that, of the organic
      components observable by 1H HR-MAS NMR, aliphatic components preferentially sorb
      to the clay surface, while carbohydrates and amino acids mainly remain in the
      supernatant. These results may help explain the highly aliphatic nature of
      organic matter associated with clay fractions in natural soils and sediments.
      Investigations using the synthetic mixtures demonstrate a specific interaction
      between the clay surface and the polar region in 1-palmitoyl-3-stearoyl-rac
      glycerol. Similar observations were obtained with natural soil extracts. The
      results presented have important implications for understanding the role of
      organoclay complexes in natural processes, and provides preliminary evidence that
      HR-MAS NMR is a powerful analytical technique for the investigation of organoclay
      complex structure and conformation.

PMID- 16649756
TI  - Liquid crystal nanoparticles prepared as miniemulsions.
AB  - Liquid crystal nanoparticles using the low molecular weight liquid crystal E7 are
      prepared by a miniemulsion approach with a droplet size between 180 and 630 nm.
      The sizes of liquid crystal droplets prepared in this work are one of the
      smallest sizes ever reported for liquid crystals, and they are considerably
      dependent on the type and amount of the surfactant used, as well as on the amount
      of hexadecane. Furthermore, the behavior of a liquid crystal confined to small
      droplets is investigated. DSC measurements reveal a large shift in the nematic
      isotropic phase transition temperature. Further investigations on liquid crystal
      droplets are carried out using AFM measurements showing that these particles have
      an order of the liquid crystal molecules within the droplets. Light scattering
      measurements yield the temperature dependence of the anisotropy and the temporal
      stability of the droplets. An effect of the director fluctuations within the
      droplets on dynamic depolarized scattering was found.

PMID- 16649757
TI  - Vesicle-micelle transition in mixtures of dioctadecyldimethylammonium chloride
      and bromide with nonionic and zwitterionic surfactants.
AB  - We have investigated the effect of mixing spontaneously formed dispersions of the
      cationic vesicle-forming dioctadecyldimethylammonium chloride and bromide (DODAX,
      with X being anions Cl- (C) or Br- (B)) with solutions of the micelle-forming
      nonionic ethylene oxide surfactants penta-, hepta-, and octaethyleneglycol mono-n
      dodecyl ether, C12E(n) (n = 5, 7, and 8), and the zwitterionic 3-(N-hexadecyl-N,N
      dimethylammonio)propane sulfonate (HPS). We used for this purpose differential
      scanning calorimetry (DSC), turbidity, and steady-state fluorescence spectroscopy
      to investigate the vesicle-micelle (V-M) transition yielded by adding C12E(n) and
      HPS to 1.0 mM vesicle dispersions of DODAC and DODAB. The addition of these
      surfactants lowers the gel-to-liquid crystalline phase transition temperature
      (T(m)) of DODAC and DODAB, and the transition becomes less cooperative, that is,
      the thermogram transition peak shifts to lower temperature and broadens to
      disappear when the V-M transition is complete, the vesicle bilayer becomes less
      organized, and the T(m) decreases, in agreement with measurements of the
      fluorescence quantum yield of trans-diphenylpolyene (t-DPO) fluorescence
      molecules incorporated in the vesicle bilayer. Turbidity data indicate that the V
      M transition comes about in three stages: first surfactants are solubilized into
      the vesicle bilayer; after saturation, the vesicles are ruptured, and, finally,
      the vesicles are completely solubilized and only mixed micelles are formed. The
      critical points of bilayer saturation and vesicle solubilization were obtained
      from the turbidity and fluorescence curves, and are reported in this
      communication. The solubility of DODAX is stronger for C12E(n) than it is for
      HPS, meaning that C12E(n) solubilizes DODAX more efficiently than does HPS. The
      surfactant solubilization depends slightly on the counterion, and varies
      according to the sequence C12E5 > C12E7 > C12E8 > HPS.

PMID- 16649758
TI  - Controlled association in suspensions of charged nanoparticles with a weak
      polyelectrolyte.
AB  - The properties of high-pH suspensions of mixtures of silica with low-molecular
      weight samples of the water-soluble polymer polyethylenimine (PEI) have been
      studied. At pH > 10 and low ionic strength, silica nanoparticles are stabilized
      by a negative surface charge, and PEI has only a very low positive charge. The
      adsorption of PEI induces a localized positive charge on the segments of polymer
      closest to the silica surface. The parts of the molecule furthest away from the
      surface have little charge because of the high pH of the medium. The polymer
      covered particle remains negatively charged, imparting some electrostatic
      stabilization. Suspensions of silica and low-molecular-weight PEI are low
      viscosity fluids immediately after mixing, but aggregation occurs leading to the
      eventual gelation (or sedimentation at lower concentrations) of these mixtures,
      indicating colloidal instability. The gelation time passes through a minimum with
      increasing surface coverage. The rate of gelation increases exponentially with
      molecular weight: for molecular weight > or = 10,000 Da PEI, the instability is
      so severe that uniform suspensions cannot be produced using simple mixing
      techniques. The gelation rates increase rapidly with temperature, ionic strength,
      and reduction in pH. The rate of gelation increases with increasing particle
      concentration at low surface coverage but decreases at high coverage as a
      consequence of a small increase in pH. Gels are broken by application of high
      shear into aggregates that re-gel more rapidly than the original discrete coated
      particles.

PMID- 16649759
TI  - Effect of emulsifier type on droplet disruption in repeated shirasu porous glass
      membrane homogenization.
AB  - The influence of various emulsifier types (anionic, nonionic, and zwitterionic)
      on the mean particle size, transmembrane flux, and membrane fouling in repeated
      membrane homogenization using a Shirasu porous glass (SPG) membrane has been
      investigated. Oil-in-water (O/W) emulsions (40 wt % corn oil stabilized by 0.06-2
      wt % sodium dodecyl sulfate (SDS) or 0.1-2 wt % Tween 20 at pH 3 or 0.5-2 wt %
      beta-lactoglobulin (beta-Lg) at pH 7) were prepared by passing coarsely
      emulsified feed mixtures five times through the membrane with a mean pore size of
      8.0 microm under the transmembrane pressure of 100 kPa. The flux increased as the
      number of passes increased, tending to a maximum limiting value. The maximum flux
      for the Tween 20-stabilized emulsions (5-47 m3.m(-2).h(-1)) was smaller than that
      for the SDS-stabilized emulsions (29-60 m3.m(-2).h(-1)) because less energy was
      needed for the disruption of a SDS-stabilized droplet due to the lower
      interfacial tension. The mean particle size after five passes was 4.1-6.8 and 6.4
      8.7 mum for 0.1-2 wt % SDS and Tween 20, respectively. The flux in the presence
      of beta-Lg was much smaller than that in the presence of SDS and Tween 20, which
      was a consequence of more pronounced membrane fouling, due to the protein
      adsorption to the membrane surface. After five passes through the membrane, the
      fouling resistance in the presence of 2 wt % beta-Lg (1.1 x 10(10) 1/m) was 2
      orders of magnitude higher than that for 0.5 wt % Tween 20 and an order of
      magnitude higher than the membrane resistance. If a clean membrane was used in
      the fifth pass, a 2-fold reduction of the fouling resistance was observed.

PMID- 16649760
TI  - Effect of block length, polydispersity, and salt concentration on PEO-PDEAMA
      block copolymer structures in dilute solution.
AB  - A series of poly(ethylene oxide)-block-poly(N,N-diethylaminoethyl methacrylate)
      (PEO-PDEAMA) block copolymers with relatively high polydispersity (1.36 < PDI <
      1.96) have been prepared to determine the effect that polydispersity has on the
      self-assembly of amphiphilic block copolymers in dilute solution. Because
      monodisperse macroinitiators were used for the ATRP reactions, the polydispersity
      resides within the hydrophobic block. By adjusting the relative block lengths,
      spherical micelles, wormlike micelles, vesicles, or a precipitate is formed.
      Here, we show that relatively high polydispersity in the block copolymer does not
      preclude efficient self-assembly. We also discuss the effect of increasing the
      concentration of NaCl in the systems and show that this can result in a shift
      from one morphology to another. These shifts are reversible in some cases, but
      for PEO12-PDEAMA39, this method allows access to giant vesicles of between 500 nm
      and 1 microm in diameter.

PMID- 16649761
TI  - Effect of steric, double-layer, and depletion interactions on the stability of
      colloids in systems containing a polymer and an electrolyte.
AB  - Experiments carried out by Stenkamp et al. [Stenkamp, V. S.; McGuiggan, P.; Berg,
      J. C. Langmuir 2001, 17, 637.] have shown that polystyrene latexes can be
      restabilized at sufficiently high electrolyte concentrations in the presence of
      an amphiphilic block copolymer [poly(ethylene oxide)-poly(propylene oxide)
      poly(ethylene oxide) (PEO-PPO-PEO)] At even higher electrolyte concentrations,
      the systems can again be destabilized. The present paper attempts to explain the
      restabilization through the dominance of steric interactions and the
      destabilization through the dominance of depletion interactions. Because of
      salting out, as the concentration of electrolyte increases, the polymer molecules
      are increasingly precipitated onto the surface of the latex particles and, at
      sufficiently high electrolyte concentrations, form, in addition, aggregates. The
      precipitation onto the latex particles generates steric repulsion, which is
      responsible for the restabilization, whereas the formation of aggregates
      generates depletion interactions, which are responsible for destabilization.

PMID- 16649762
TI  - Self-assembly of spherical particles on an evaporating sessile droplet.
AB  - Particles adsorbed on the surface of a droplet form three-dimensional packings
      when the droplet evaporates. We study the final packings when the liquid droplet
      is attached to a solid substrate. In contrast to a droplet evaporating away from
      a substrate, here the final packings are highly dependent on both the number of
      particles and the contact angle between the droplet and the surface. Simple
      geometrical constraints quantitatively determine the parameter regions that
      particular packings can form.

PMID- 16649763
TI  - Synthesis and characterization of charged polystyrene-acrylic acid latex
      particles.
AB  - Novel, monodisperse charged colloidal particles of polystyrene cross linked with
      divinylbenzene and surface-grafted with acrylic acid were synthesized by emulsion
      polymerization and were characterized by estimating the dissociable surface
      charge by conductivity titration, the particle effective charge by conductivity
      verses particle concentration, and the particle size by dynamic light scattering
      and atomic force microscopy. The structural ordering and dynamics were
      investigated as a function of the volume fraction of the particles using static
      and dynamic light scattering, respectively. Furthermore, from the electrophoresis
      measurements, these particles are found to have a high salt tolerance due to
      increases in charge as a function of salt concentration.

PMID- 16649764
TI  - Plastic-to-elastic transition in aggregated emulsion networks, studied with
      atomic force microscopy-confocal scanning laser microscopy microrheology.
AB  - In this paper, we demonstrate how the simultaneous application of atomic force
      microscopy (AFM) and confocal scanning laser microscopy (CSLM) can be used to
      characterize the (local) rheological properties of soft condensed matter at
      micrometer length scales. Measurement of AFM force curves as a function of the
      indentation amplitude and speed (magnitude and direction) can produce a
      "mechanical fingerprint" that contains information about material stiffness,
      hysteretic losses, and time scales for stress relaxation and/or network recovery.
      The simultaneous CSLM visualization of changes in the material's structure
      provides complementary information about how the material accommodates the
      indentation load. Since these experiments are done on areas of O(100 microm2) on
      materials having a surface of O(1 cm2), the measurements can be repeated on
      "fresh" material many times, contrary to traditional rheometers where the whole
      sample is loaded at once. As a particular example, we consider the case of a
      network of aggregated water-in-oil (W/O) emulsion droplets, in which the
      mechanical behavior changes drastically over time. Whereas the freshly prepared
      material shows a soft plastic behavior, after a time lapse of several weeks, the
      very same sample shows a much stiffer and elastic response. This drastic change
      in behavior is clearly reflected both in the signature of the AFM force curves
      and in (the reversibility of) the structural deformations observed with CSLM. The
      fact that these drastic mechanical changes take place without significant changes
      in the structure of the material (before loading) indicates that the stiffening
      of the droplet network is caused by an increase in the strength of the bonds
      between droplets. A remarkable finding for the elastic droplet network is that,
      while the structure recovers completely after the indenter is taken out, there is
      still an appreciable hysteresis in the force curves, indicating that dissipation
      also occurs. This hysteresis was not found to depend on the indentation speed.

PMID- 16649765
TI  - Tailoring of horseradish peroxidase activity in cationic water-in-oil
      microemulsions.
AB  - Horseradish peroxidase (HRP) in cationic water-in-oil (W/O) microemulsions has
      always been ignored in reverse micellar enzymology, mainly because cationic
      surfactants are inhibitors of enzyme peroxidase. In the present study, for the
      first time, we have successfully introduced the cationic W/O microemulsion as an
      attractive host for efficient HRP activity. To this notion, much improved
      activity of HRP was observed in the W/O microemulsion of cetyltrimethylammonium
      bromide (CTAB) with an increase in n-hexanol concentration and W0
      ([water]/[surfactant]), presumably due to the increased interfacial area of the
      microemulsions. In support of our above observation, six surfactants were
      synthesized with an increased headgroup size where the methyl groups of CTAB were
      subsequently replaced by the n-propyl and 2-hydroxyethyl groups, respectively, to
      prepare mono-, di-, and tripropylated/hydroxyethylated n-hexadecylammonium
      bromide. The peroxidase activity enhanced with headgroup size and also followed
      an overall trend similar to that found in the case of CTAB. Possibly, the reduced
      positive charge density at the augmented interfacial area by means of increase,
      either in headgroup size, cosurfactant concentration, and/or W0, is not capable
      of inactivating HRP. Also, the larger space at the interface may facilitate
      easier solubilization of the enzyme and increase the local concentration of
      enzyme and substrate, leading to the higher activity of HRP. The best activity
      was obtained with surfactant N-hexadecyl-N,N,N-tripropylammonium bromide, the
      highest ever found in any cationic W/O microemulsions, being almost 3 times
      higher than that found in water. Strikingly, this observed highest activity is
      comparable with that observed in an anionic bis(2-ethylhexyl)sulfosuccinate
      sodium salt (AOT)-based system, the best W/O microemulsions used for HRP.

PMID- 16649766
TI  - Roles of the textural and surface chemical properties of activated carbon in the
      adsorption of acid blue dye.
AB  - This study has demonstrated the use of empirical modeling in resolving the
      effects of individual carbon properties on acid blue dye adsorption. Acid blue
      dye adsorption tests were conducted on activated carbons prepared from bagasse by
      physical (CO2) and chemical (ZnCl2, MgCl2 and CaCl2) techniques. Empirical models
      based on the carbon textural (surface area and pore size) properties and the
      surface chemistry inferred from heteroatom (C,H, N, and S) concentration and
      carbon surface pH were used to resolve the effects of individual carbon
      properties on acid blue dye adsorption. This form of analysis was conducted to
      optimize carbon preparation properties, forming the foundation for tailor-making
      adsorbents from bagasse suitable for acid dye adsorption. A series of statistical
      analyses (partial F-tests to establish the parameter significance) measured
      variants including the mean square error, r2 and adjusted r2, normality, and
      randomness of residuals, and formed the basis for testing the adequacy of these
      models. The empirical models suggest that a combination of suitable pore
      structure and distinct basic surface chemistry generated by sulfur- and nitrogen
      based groups, which were also elucidated by Fourier transform infrared
      spectroscopy, is necessary to promote acid dye adsorption.

PMID- 16649767
TI  - Ordered mesoporous carbon as an efficient and reversible adsorbent for the
      adsorption of fullerenes.
AB  - An ordered mesoporous carbon, CMK-3, was synthesized using a mesoporous siliceous
      material, SBA-15, as the template. CMK-3 was characterized and used for the
      adsorption of fullerenes C60 and C70. It was found that the adsorption capacity
      of CMK-3 is 4 times higher than that of activated carbon. The adsorption
      equilibrium isotherms of C60 and C70 on CMK-3 were studied for both single and
      binary systems. The reversibility of fullerene adsorption on CMK-3 was also
      explored. The results showed that CMK-3 is an effective and reversible adsorbent
      for the separation of fullerenes by adsorption.

PMID- 16649768
TI  - Surface plasmon resonance spectroscopy study of electrostatically adsorbed
      layers.
AB  - The use of 4-(dimethylamino)pyridine to form an adhesion layer for the adsorption
      of anionic polyelectrolytes on gold surfaces is investigated. In situ surface
      plasmon resonance spectroscopy is used to monitor the changes in thickness of the
      adsorbed layers as a function of pH changes. Weak (poly(acrylate)) and strong
      (poly(styrenesulfonate)) polyelectrolytes have been studied. Although 4
      (dimethylamino)pyridine is weakly bound to gold, it is not displaced by these
      polyelectrolytes and acts as an adhesion layer. The relationship of the
      interaction of anionic polyelectrolytes with 4-(dimethylamino)pyridine-modified
      planar gold and gold nanoparticles is discussed.

PMID- 16649769
TI  - Porous structures of polymer films prepared by spin coating with mixed solvents
      under humid condition.
AB  - We investigate the effects of interfacial energy between water and solvent as
      well as polymer concentration on the formation of porous structures of polymer
      films prepared by spin coating of cellulose acetate butyrate (CAB) in mixed
      solvent of tetrahydrofuran (THF) and chloroform under humid condition. The
      interfacial energy between water and the solvent was gradually changed by the
      addition of chloroform to the solvent. At a high polymer concentration (0.15
      g/cm3 in THF), porous structures were limited only at the top surfaces of CAB
      films, regardless of interfacial energies, due to the high viscosity of the
      solution. At a medium concentration (approximately 0.08 g/cm3 in THF), CAB film
      had relatively uniform pores at the top surface and very small pores inside the
      film because of the mixing of the water droplets with THF solution. When
      chloroform was added to THF, pores at the inner CAB film had a comparable size
      with those at the top surface because of the reduced degree of the mixing between
      the water droplets and the mixed solvent. A further decrease in polymer
      concentration (0.05 g/cm3 in THF) caused the final films to have a two-layer
      porous structure, and the size of pores at each layer was almost the same.

PMID- 16649770
TI  - Interaction of mono- and diisocyanoazulenes with gold surfaces: first examples of
      self-assembled monolayer films involving azulenic scaffolds.
AB  - The formation and properties of a new class of self-assembled monolayers (SAM) of
      aryl isocyanides and diisocyanides based on the nonbenzenoid azulenic framework
      have been investigated using FTIR spectroscopy and ellipsometry. Syntheses of
      several new members of the isocyanoazulene family, a recently established type of
      aryl isocyanides, are reported as well. The FTIR spectra for the isocyanoazulene
      derivatives absorbed on the gold surface indicate the terminal upright
      coordination of every isocyanoazulene molecule studied. In addition, the
      ellipsometric thicknesses have been measured and are consistent with those
      calculated for single monolayers of the isocyanides oriented along the surface
      normal. Unlike SAMs of some benzenoid aryl isocyanides, the nonbenzenoid
      isocyanoazule-based SAMs proved resistant to oxidation, oligomerization, and
      isomerization into the corresponding nitriles under ambient conditions, which is
      an important prerequisite to their future applications.

PMID- 16649771
TI  - Nanoimaging and spectroscopic analysis of rubber/ZnO interfaces by energy
      filtering transmission electron microscopy.
AB  - Energy-filtering transmission electron microscopy (EFTEM) was employed for
      investigating interactions between rubber and ZnO particles in the accelerated
      vulcanization process. Combining elemental mapping and electron energy loss
      spectroscopy (EELS) by EFTEM enabled the characterization of the interfaces with
      spatial resolutions of less than 10 nm and with high elemental detection
      sensitivity. We found that a sulfur- and zinc-rich compound was generated around
      ZnO particles, and that product was then revealed to be ZnS-generated as a
      byproduct in the accelerated vulcanization process. Through this study, it is
      indicated that the accelerated vulcanization with ZnO does not occur uniformly in
      the rubber matrix; it occurs locally around ZnO particles at a higher reaction
      rate, implying that the rubber network structure is not uniform on the nanoscale.

PMID- 16649772
TI  - Thermodynamic and neutron scattering study of hydrogen adsorption in two
      mesoporous ordered carbons.
AB  - Two mesoporous ordered carbon materials (MOCs) have been synthesized from silica
      templates by using sucrose as the carbon precursor. The textural characterization
      using Ar, N2, and CO2 adsorption combined with neutron diffraction showed that
      the two samples exhibit a significant microporous volume close to 0.5 cm3/g and
      an ordered network of mesopores. For both MCM48 and SBA15 templated carbons,
      adsorption first proceeds with the filling of micropores and then by the filling
      of mesopores with an adsorption energy close to the enthalpy of vaporization of
      bulk hydrogen. The hydrogen isosteric heat of adsorption in the micropores (6-8
      kJ/mol) is significantly larger than that on the graphite surface (approximately
      4 kJ/mol) but still too small for a reasonable use of these MOCs as hydrogen
      adsorbents for storage at room temperature. The neutron scattering study showed
      that the structure at 10 K of the adsorbed deuterium phase is poorly organized;
      it exhibits short and medium range orders of about 13 angstroms in micropores and
      about 20 angstroms in mesopores, respectively. The average distance between
      adsorbed molecules decreases with coverage by about 10%. In the mesopores, the
      diffracted line is consistent with a pseudohexagonal packing.

PMID- 16649773
TI  - Mass transport of O2 and N2 in nanoporous carbon (C168 schwarzite) using a
      quantum mechanical force field and molecular dynamics simulations.
AB  - A hierarchical approach is used to calculate the single-component fluxes of N2
      and O2 in nanoporous carbon molecular sieves (represented by C168 schwarzite)
      over a wide range of pressures and pressure drops. The self- and corrected
      diffusivities are calculated using equilibrium molecular dynamics simulations
      with force fields for the gas-carbon interactions obtained from quantum
      mechanical calculations. These results are combined with previously reported
      adsorption isotherms of N2 and O2 in C168 to obtain transport diffusivities and,
      by use of the Fick's equation of mass transport, to obtain single-component
      fluxes across the membrane. The diffusion coefficients and fluxes are also
      calculated using an empirical potential, which has been obtained by fitting low
      coverage adsorption data of N2 and O2 on a planar graphite sheet. By analyzing
      the diffusivities calculated with the ab initio potential in the limit of
      infinite dilution over the temperature range from 80 to 450 K, it is observed
      that the N2/O2 separation is energetically driven and a high selectivity of O2
      over N2 can be obtained at low temperatures. However, with the empirical
      potential both the energetic and entropic contributions to selectivity were found
      to be close to unity. Similarly, by calculating single-component fluxes and ideal
      selectivities at 300 K and finite pressures it is found that the ab initio
      potential better explains the large O2/N2 selectivities of similarly sized
      molecules that have been observed experimentally. An interesting reversal in
      ideal selectivity is observed by adjusting the pressure at the two ends of the
      membrane. As a consequence, we predict that a highly selective kinetic separation
      in favor of either nitrogen or oxygen could be obtained with the same membrane
      depending on the operating conditions.

PMID- 16649774
TI  - Molecular dynamics simulations of multilayer films of polyelectrolytes and
      nanoparticles.
AB  - We performed molecular dynamics simulations of multilayer assemblies of flexible
      polyelectrolytes and nanoparticles. The film was constructed by sequential
      adsorption of oppositely charged polymers and nanoparticles in layer-by-layer
      fashion from dilute solutions. We have studied multilayer films assembled from
      oppositely charged polyelectrolytes, oppositely charged nanoparticles, and mixed
      films containing both nanoparticles and polyelectrolytes. For all studied
      systems, the multilayer assembly proceeds through surface overcharging after
      completion of each deposition step. There is almost linear growth in the surface
      coverage and film thickness. The multilayer films assembled from nanoparticles
      show better layer stratification but at the same time have higher film roughness
      than those assembled from flexible polyelectrolytes.

PMID- 16649775
TI  - Iron nanoparticles: the core-shell structure and unique properties for Ni(II)
      sequestration.
AB  - It is demonstrated that iron nanoparticles function as a sorbent and a reductant
      for the sequestration of Ni(II) in water. A relatively high capacity of nickel
      removal is observed (0.13 g Ni/g Fe, or 4.43 mequiv Ni(II)/g), which is over 100%
      higher than the best inorganic sorbents available. High-resolution X-ray
      photoelectron spectroscopy (HR-XPS) confirms that the zerovalent iron
      nanoparticles have a core-shell structure and exhibit characteristics of both
      hydrous iron oxides (i.e., as a sorbent) and metallic iron (i.e., as a
      reductant). Ni(II) quickly forms a surface complex and is then reduced to
      metallic nickel on the nanoparticle surface. The dual properties of iron
      nanoparticles may offer efficient and unique solutions for the separation and
      transformation of metal ions and other environmental contaminants.

PMID- 16649776
TI  - Equilibrium and dynamic surface tension properties of partially fluorinated
      quaternary ammonium salt gemini surfactants.
AB  - The equilibrium and dynamic surface tension properties of a partially fluorinated
      quaternary ammonium salt gemini surfactant 1,2-bis[dimethyl-(3-perfluoroalkyl-2
      hydroxypropyl)ammonium]ethane bromide (C(n)(F)C3-2-C3C(n)F, where n represents
      fluorocarbon chain lengths of 4, 6, and 8) were investigated, and the effects of
      the fluorocarbon chain length and the number of chains on them were discussed.
      The plot of the logarithm of the critical micelle concentration (cmc) against the
      fluorocarbon chain length for C(n)(F)C3-2-C3C(n)F showed a linear decrease with
      an increase in chain length. On the basis of the slope of this plot, it was found
      that the variation in cmc with respect to the chain length is large for
      fluorinated gemini surfactants. The surface tension at the cmc decreased
      significantly; this surface tension value is lower than that of conventional
      fluorinated monomeric surfactants. In particular, the lowest value was 13.7 mN m(
      1) for n = 8. Furthermore, it was confirmed that the kinetics of adsorption at
      the interface decrease with an increase in the fluorocarbon chain length and the
      concentration.

PMID- 16649777
TI  - Characterization of self-assembled organic films using differential charging in X
      ray photoelectron spectroscopy.
AB  - Differential charging is often regarded as a problem in X-ray photoelectron
      spectroscopic studies, especially for insulating or partially conducting samples.
      Application of a positive bias can reduce the effect of differential charging by
      attracting stray electrons from the system, thereby compensating for the electron
      loss. On the other hand, differential charging effect can be enhanced by the
      application of a negative bias to the sample during spectrum acquisition. The
      successful use of the differential charging technique to distinguish between
      multi- and monolayer organophosphonate films on oxide-covered silicon has been
      reported. A detailed description of this technique is now presented which shows
      how differential charging can be used as an important tool for the
      characterization of self-assembled films deposited on various surfaces. The
      dependence of this technique on the conductivity of the substrate has been
      investigated by studying the spectral behavior of the deposited films of
      phosphonic acid on conducting, semiconducting, and insulating samples (stainless
      steel, silicon, and glass). Application of either positive or negative dc
      electrical bias affects the carbon core-level (C1s) line shape and intensity,
      which is dependent on the atom's physical location above the surface.

PMID- 16649778
TI  - Measurement of the azimuthal anchoring energy of liquid crystals in contact with
      oligo(ethylene glycol)-terminated self-assembled monolayers supported on
      obliquely deposited gold films.
AB  - We report measurements of the orientations and azimuthal anchoring energies of
      the nematic liquid crystal 4-cyano-4'-pentylbiphenyl (5CB) on polycrystalline
      gold films that are deposited from a vapor at an oblique angle of incidence and
      subsequently decorated with organized monolayers of oligomers of ethylene glycol.
      Whereas the gold films covered with monolayers presenting tetra(ethylene glycol)
      (EG4) lead to orientations of 5CB that are perpendicular to the plane of
      incidence of the gold, monolayers presenting tri(ethylene glycol) (EG3) direct
      5CB to orient parallel to the plane of incidence of the gold during deposition of
      the gold film. We also measure the azimuthal anchoring energy of the 5CB to be
      smaller on the surfaces presenting EG3 (3.2 +/- 0.8 microJ/m2) as compared to EG4
      (5.5 +/- 0.9 microJ/m2). These measurements, when combined with other results
      presented in this paper, are consistent with a physical model in which the
      orientation and anchoring energies of LCs on these surfaces are influenced by
      both (i) short-range interactions of 5CB with organized oligomers of ethylene
      glycol at these surfaces and (ii) long-range interactions of 5CB with the
      nanometer-scale topography of the obliquely deposited films. For surfaces
      presenting EG3, these short- and long-range interactions oppose each other,
      leading to small net values of anchoring energies that we predict are dependent
      on the level of order in the EG3 SAM. These measurements provide insights into
      the balance of interactions that control the orientational response of LCs to
      biological species (proteins, viruses, cells) on these surfaces.

PMID- 16649779
TI  - Domain memory of mixed polymer brushes.
AB  - The nano-phase-separation in mixed polymer brushes consisting of polystyrene and
      poly(methyl methacrylate) (PS-PMMA) chains attached to a silicon surface is
      studied. The topographies of the mixed brushes are examined after they have been
      exposed to solvents which induce or erase nano-phase-separation. It is discussed
      whether the brush locally forms the same pattern every time the transition from
      the smooth and featureless to the nanopatterned state occurs ("domain memory") or
      if the local assembly of the domains emerges in a different arrangement after
      each cycle of topography switching. A memory measure parameter is introduced,
      which characterizes quantitatively the domain memory effect in the nanopattern.
      It is shown that at constant grafting density but with increasing molecular
      weight of the brush chains the memory measure parameter decreases. In contrast to
      this, brushes with constant molecular weight, but differing in grafting density,
      all have a similar domain memory. We discuss a possible origin of the domain
      memory effect in the mixed brush systems studied and point out its impact on the
      motion of nanoparticles adsorbed on top of such systems.

PMID- 16649780
TI  - Termination and water adsorption at the alpha-Al2O3 (012)-aqueous solution
      interface.
AB  - Understanding the interaction of water with metal oxide surfaces is important to
      a diverse array of fields and is essential to the interpretation of surface
      charging and ion adsorption behavior. High-resolution specular X-ray reflectivity
      was used to determine the termination of and water adsorption on the alpha-Al2O3
      (012)-aqueous solution interface. Interference features in the reflectivity data
      were used to identify the likely termination, consisting of a full Al2O3 layer
      plus an additional oxygen layer that completes the coordination shell of the
      upper aluminum site. This was further investigated through a model-independent
      inversion of the data using an error correction algorithm, which also revealed
      that there are two sites of adsorbed water above the surface. Characteristics of
      these two water sites were quantified through a model-dependent structural
      refinement, which also revealed additional layering in the interfacial water that
      gradually decays toward disordered bulk water away from the surface. Although the
      termination observed in this study differs from that assumed in past studies of
      surface charging, the density of key surface functional groups is unchanged, and
      thus, predictions of surface charging behavior are unchanged. As the pH(pzc) of
      this surface has yet to be modeled accurately, a full 3-dimensional surface
      structural analysis based on the termination observed in this study is needed so
      that the effects of surface functional group bond length changes on the pK(a)
      values can be incorporated. Consideration of the termination and sites of water
      adsorption suggest that singly coordinated oxygen groups will be the primary
      sites of ion adsorption on this surface.

PMID- 16649781
TI  - Synthesis of silanol-functionalized latex nanoparticles through miniemulsion
      copolymerization of styrene and gamma-methacryloxypropyltrimethoxysilane.
AB  - The polystyrene latex nanoparticles bearing silanol groups on their surfaces were
      successfully synthesized via miniemulsion polymerization using gamma
      methacryloxypropyltrimethoxysilane (MPS) as the functional comonomer and oil
      soluble AIBN as the initiator at neutral conditions. FTIR and 29Si NMR spectra
      showed that the condensation of silanol groups was suppressed effectively. zeta
      potential and XPS analyses demonstrated that the silanol groups were enriched at
      the surfaces of the latex particles and could be tailored by MPS concentration.
      These silanol-functionalized latex particles could be easily coated with silica
      or other inorganic or organic compounds to prepare novel hybrid particles and
      hollow microspheres.

PMID- 16649782
TI  - Homophilic interactions between cadherin fragments at the single molecule level:
      an AFM study.
AB  - We report measurements of the adhesion forces between single E-cadherin fragments
      anchored on solid surfaces. These fragments consist of the two outermost
      extracellular domains of the protein. The specificity of the measured rupture
      forces was demonstrated by Ca2+ exchange experiments. Two series of experiments
      were performed using two linkers of different rigidity and length. We find that
      the pull-off force is distributed with a maximum value independent of the linker
      and logarithmically dependent on the velocity of separation of the two surfaces.
      Our dynamical results are compatible with previous flow chamber experiments
      performed with the same fragments and can be compared from a different
      perspective with previously reported AFM experiments on the full-length
      extracellular domain of the VE-cadherin. Interestingly, using a rigid linker, we
      have been able for the first time to evidence the deformation of the cadherin
      molecule under mechanical stress, a piece of information not accessible with more
      classical grafting strategies.

PMID- 16649783
TI  - Scanning force microscopy and fluorescence microscopy of microcontact printed
      antibodies and antibody fragments.
AB  - Unlabeled primary immunoglobulin G (IgG) antibodies and its F(ab')2 and Fc
      fragments were attached to oxygen-plasma-cleaned glass substrates using either
      microcontact printing (MCP) or physical adsorption during bath application from
      dilute solutions. Fluorescently labeled secondary IgGs were then bound to surface
      immobilized IgG, and the relative surface coverage was determined by measuring
      the fluorescence intensity. Results indicated that the surface coverage of IgG
      increased with increasing protein solution concentration for both MCP and bath
      applied IgG and that a greater concentration of IgG was transferred to a glass
      substrate using MCP than during physisorption during bath applications. Scanning
      force microscopy (SFM) showed that patterned MCP IgG monolayers were 5 nm in
      height, indicating that IgG molecules lie flat on the substrate. After incubation
      with a secondary IgG, the overall line thickness increased to around 15 nm,
      indicating that the secondary IgG was in a more vertical orientation with respect
      to the substrate. The surface roughness of these MCP patterned IgG bilayers as
      measured by SFM was observed to increase with increasing surface coverage.
      Physisorption of IgG to both unmodified patterned polydimethylsiloxane (PDMS)
      stamps and plasma-cleaned glass substrates was modeled by Langmuir adsorption
      kinetics yielding IgG binding constants of K(MCP) = 1.7(2) x 10(7) M(-1) and
      K(bath) = 7.8(7) x 10(5) M(-1), respectively. MCP experiments involving primary
      F(ab')2 and Fc fragments incubated in fluorescently labeled fragment-specific
      secondary IgGs were carried out to test for the function and orientation of IgG.
      Finally, possible origins of MCP stamping defects such as pits, pull outs,
      droplets, and reverse protein transfer are discussed.

PMID- 16649784
TI  - Controlling DNA orientation on mixed ssDNA/OEG SAMs.
AB  - We present and characterize a mixed self-assembled monolayer (SAM) consisting of
      single-stranded oligonucleotide (ssDNA)- and oligo(ethylene glycol) (OEG)
      terminated thiols. The ssDNA/OEG SAMs are prepared by simultaneous coadsorption
      from a common thiol solution over a broad range of compositions. Electron
      spectroscopy for chemical analysis (ESCA) is used to measure the surface coverage
      of ssDNA, whereas surface plasmon resonance (SPR) sensor is used to measure the
      hybridization of complementary ssDNA and protein resistance. Through the
      complementary use of these techniques, we find that the composition of OEG in the
      assembly solution controls a key parameter: the surface coverage of ssDNA on the
      surface. There is evidence that it influences the orientation of the immobilized
      ssDNA probes. Lower OEG concentrations yield a surface with higher ssDNA coverage
      and less favorable orientation, whereas higher OEG concentrations produce a
      surface with lower DNA coverage and more favorable orientation. Competition
      between these two effects controls the hybridization efficiency of the ssDNA
      surface. Compared to ssDNA surfaces prepared with other diluent thiols, the use
      of OEG improves the protein resistance of the surface, making it more broadly
      applicable.

PMID- 16649785
TI  - Exploring the interaction of ruthenium(II) polypyridyl complexes with DNA using
      single-molecule techniques.
AB  - Here we explore DNA binding by a family of ruthenium(II) polypyridyl complexes
      using an atomic force microscope (AFM) and optical tweezers. We demonstrate using
      AFM that Ru(bpy)2dppz2+ intercalates into DNA (K(b) = 1.5 x 10(5) M(-1)), as does
      its close relative Ru(bpy)2dppx2+ (K(b) = 1.5 x 10(5) M(-1)). However,
      intercalation by Ru(phen)3(2+) and other Ru(II) complexes with K(b) values lower
      than that of Ru(bpy)2dppz2+ is difficult to determine using AFM because of
      competing aggregation and surface-binding phenomena. At the high Ru(II)
      concentrations required to evaluate intercalation, most of the DNA strands
      acquire a twisted, curled conformation that is impossible to measure accurately.
      The condensation of DNA on mica in the presence of polycations is well known, but
      it clearly precludes the accurate assessment by AFM of DNA intercalation by most
      Ru(II) complexes, though not by ethidium bromide and other monovalent
      intercalators. When stretching individual DNA molecules using optical tweezers,
      the same limitation on high metal concentration does not exist. Using optical
      tweezers, we show that Ru(phen)2dppz2+ intercalates avidly (K(b) = 3.2 x 10(6) M(
      1)) whereas Ru(bpy)3(2+) does not intercalate, even at micromolar ruthenium
      concentrations. Ru(phen)3(2+) is shown to intercalate weakly (i.e., at micromolar
      concentrations (K(b) = 8.8 x 10(3) M(-1))). The distinct differences in DNA
      stretching behavior between Ru(phen)3(2+) and Ru(bpy)3(2+) clearly illustrate
      that intercalation can be distinguished from groove binding by pulling the DNA
      with optical tweezers. Our results demonstrate both the benefits and challenges
      of two single-molecule methods of exploring DNA binding and help to elucidate the
      mode of binding of Ru(phen)3(2+).

PMID- 16649786
TI  - Particle tracking using confocal microscopy to probe the microrheology in a phase
      separating emulsion containing nonadsorbing polysaccharide.
AB  - Brownian diffusion of fluorescent microspheres (0.21, 0.5, and 0.89 microm
      diameter) in conjunction with confocal microscopy has been used to monitor the
      microrheology of phase-separated regions in a protein-stabilized oil-in-water
      emulsion containing various low concentrations of a nonadsorbing polysaccharide,
      xanthan gum. The sensitivity and reliability of the technique has been
      demonstrated in test experiments on (i) aqueous glycerol solutions and (ii)
      concentrated surfactant-stabilized emulsions (30-60 vol % oil, 1-2 wt % Tween
      20). From particle tracking measurements on the caseinate-stabilized emulsions
      (30 vol % oil, 1.4 wt % sodium caseinate, pH 7) containing xanthan (0.03-0.07 wt
      %), the apparent viscosity in the oil-droplet-rich regions has been estimated to
      be up to 10(3) times higher than that in the phase-separated xanthan-rich
      regions. This means that our previously determined shape relaxation times for
      xanthan-containing blobs in the same systems can be attributed to the dominant
      viscoelasticity of the surrounding regions of concentrated oil droplets and not
      to the rheology of the xanthan-rich blobs themselves. These data provide clear
      and unequivocal evidence for the dominant role of the interconnected depletion
      flocculated network of oil droplets in the physicochemical mechanism by which
      hydrocolloid thickeners control the creaming instability of concentrated oil-in
      water emulsions.

PMID- 16649787
TI  - Interaction forces measured using AFM between colloids and surfaces coated with
      both dextran and protein.
AB  - Both proteins and polysaccharides are biopolymers present on a bacterial surface
      that can simultaneously affect bacterial adhesion. To better understand how the
      combined presence of proteins and polysaccharides might influence bacterial
      attachment, adhesion forces were examined using atomic force microscopy (AFM)
      between colloids (COOH- or protein-coated) and polymer-coated surfaces (BSA,
      lysozyme, dextran, BSA+dextran and lysozyme+dextran) as a function of residence
      time and ionic strength. Protein and dextran were competitively covalently bonded
      onto glass surfaces, forming a coating that was 22-33% protein and 68-77%
      dextran. Topographic and phase images of polymer-coated surfaces obtained with
      tapping mode AFM indicated that proteins at short residence times (<1 s) were
      shielded by dextran. Adhesion forces measured between colloid and polymer-coated
      surfaces at short residence times increased in the order protein+dextran < or =
      protein < dextran. However, the adhesion forces for protein+dextran-coated
      surface substantially increased with longer residence times, producing the
      largest adhesion forces between polymer coated surfaces and the colloid over the
      longest residence times (50-100 s). It was speculated that with longer
      interaction times the proteins extended out from beneath the dextran and
      interacted with the colloid, leading to a molecular rearrangement that increased
      the overall adhesion force. These results show the importance of examining the
      effect of the combined adhesion force with two different types of biopolymers
      present and how the time of interaction affects the magnitude of the force
      obtained with two-polymer-coated surfaces.

PMID- 16649788
TI  - Real-time monitoring of polymer swelling on the nanometer scale by atomic force
      microscopy.
AB  - The swelling of a polymer surface has been monitored in real time on the
      nanometer scale by atomic force microscopy (AFM). After modification by oxygen
      plasma treatment, poly(p-phenylene terephthalamide) (PPTA) displays a
      characteristic nanostructured surface morphology consisting of high-lying
      features alternating with topographically depressed areas. Selective swelling of
      the least cross-linked, depressed areas after the adsorption of ambient water or
      water from saturated humid atmospheres was observed by tapping mode AFM operated
      in the attractive interaction regime. The swollen areas could be distinguished
      from the nonswollen ones by local variations in the sample indentation made by
      the AFM tip when imaging in the tapping mode repulsive interaction regime.
      Monitoring the swelling of the plasma-treated polymer surface provided a means to
      reveal the nanometer-scale heterogeneity that this type of treatment creates on
      the polymer surface, which is something that would not be possible otherwise.
      Measurement of AFM tip-sample adhesion forces evidenced rapid water adsorption
      onto the oxygen plasma-treated surface, supporting the idea of water-induced
      swelling. This high hydrophilicity was interpreted as arising from the
      incorporation of polar oxygen functionalities, as demonstrated by X-ray
      photoelectron spectroscopy (XPS).

PMID- 16649789
TI  - Atomically flat gold on elastomeric substrate.
AB  - We present a procedure to fabricate extremely smooth Au films supported on thin
      elastomeric (PDMS) substrates. Minimum rms roughness and largest grain size are
      obtained using Si wafers, coated with native oxide and release layers, as
      templates for the growth of thermally evaporated Au films. The wafers are held at
      a temperature of 300 degrees C during deposition. The Au films, up to 200 nm
      thick, are then transferred onto poly(dimethylsiloxane) substrates which have
      been previously surface-functionalized with a (3-mercaptopropyl)trimethoxysilane
      adhesion layer. The resulting Au films have been found by AFM to be extremely
      smooth with rms-roughness 2.5-4 angstroms and to exhibit a crystalline morphology
      with flat grains >500 nm in size. Thinner films, down to 20 nm, are grown at
      lower temperature and are comparably smooth, but with a loss in crystalline
      morphology. We compare the results of this optimized procedure with other gold
      films grown on mica sheets as templates and to those produced using Ti-O-Si
      interfacial chemistry.

PMID- 16649790
TI  - Thermal Analysis of Adsorbed Poly(methyl methacrylate) on Silica.
AB  - Modulated differential scanning calorimetry has been used to quantify the glass
      transitions of small adsorbed amounts of poly(methyl methacrylate) (PMMA) on
      silica. While a relatively narrow, single glass transition was found for bulk
      PMMA, broader two-component transitions were found for the adsorbed polymer. A
      two-state model based on loosely bound polymer (glass transition similar to bulk)
      and more tightly bound polymer (glass transition centered around 156 degrees C)
      was used to interpret the thermograms. On the basis of this model, the amount of
      tightly bound polymer was found to be approximately 1.3 mg/m2, corresponding to a
      1.1 nm thick layer. The change in heat capacity for the tightly bound polymer at
      the glass transition temperature was estimated to be about 16% of that of the
      bulk polymer.

PMID- 16649791
TI  - Liquid nanodroplets spreading on chemically patterned surfaces.
AB  - Controlling the spatial distribution of liquid droplets on surfaces via surface
      energy patterning can be used to deliver material to specified regions via
      selective liquid/solid wetting. Although studies of the equilibrium shape of
      liquid droplets on heterogeneous substrates exist, much less is known about the
      corresponding wetting kinetics. Here we present large-scale atomistic simulations
      of liquid nanodroplets spreading on chemically patterned surfaces. Results are
      presented for lines of polymer liquid (droplets) on substrates consisting of
      alternating strips of wetting (equilibrium contact angle theta0 = 0 degrees) and
      nonwetting (theta0 approximately 90 degrees) material. Droplet spreading is
      compared for different wavelength lambda of the pattern and strength of surface
      interaction on the wetting strips. For small lambda, droplets partially spread on
      both the wetting and nonwetting regions of the substrate to attain a finite
      contact angle less than 90 degrees. In this case, the extent of spreading depends
      on the interaction strength in the wetting regions. A transition is observed such
      that, for large lambda, the droplet spreads only on the wetting region of the
      substrate by pulling material from nonwetting regions. In most cases, a precursor
      film spreads on the wetting portion of the substrate at a rate strongly dependent
      on the width of the wetting region.

PMID- 16649792
TI  - C-H...F hydrogen bonding: the origin of the self-assemblies of bis(2,2'-difluoro
      1,3,2-dioxaborine).
AB  - The effect of the molecular structure on the self-assembly of specially designed
      two-core 1,3,2-dioxaborines has been studied with various techniques. It was
      found that the molecules spontaneously adsorbed on HOPG surfaces and self
      organized into well-ordered two-dimensional (2D) monolayers. The structural
      details of the 2D assemblies were investigated by scanning tunneling microscopy
      (STM). From X-ray analysis of the corresponding three-dimensional (3D) crystal
      and from theoretical calculation, we were able to reveal the driving force behind
      the specific self-assembly. The C-H...F hydrogen bonding between the ortho carbon
      of the phenyl ring and the fluorine of the BF2 group plays an important role in
      the formation of the adlayers. The different electron affinities and geometries
      of the molecules affect the intermolecular interactions which further lead to
      different properties in the bulk materials.

PMID- 16649793
TI  - Surface pressure driven supramolecular architectures from mixed H-aggregates of
      dye-capped azobenzene derivative.
AB  - We demonstrate a soft chemical approach for the synthesis of dimensionally
      dictated functionalized mesostructures by continuous tuning of the surface
      molecular density of a photoreceptable molecule (E)-1-(3-chloro-4
      (octyloxy)phenyl)-2-phenyldiazene (compound 1) with Rhodamine B (Rh B). Highly
      oriented cylindrical microtubules with a hollow center running the entire
      distance of the assembly in a parallel-packed configuration were formed at the
      air-water interface. The surface tension driven self-organized structures were
      evidenced from electronic absorption and steady-state fluorescence spectroscopy
      in conjunction with optical, polarizing, and epifluorescence microscopy and
      microspectroscopy; the structural building blocks were identified to be mixed H
      aggregates from compound 1 and Rh B of 1:1 stoichiometry, corroborated by a blue
      shift in the characteristic absorption features. The appearance of a crossover
      point (apparent isosbestic point) instead of a sharp defined isosbestic point in
      the absorption spectra signified the formation of mixed H-aggregates from trans
      azobenzenes in ion-dipole interaction with the charged Rh B. Increasing the
      temperature induced an end-to-end self-assembly of the hollow tubules, and
      photoisomerization of compound 1 did not serve as a trigger to induce self
      organization. A nonfluorescent planar crystalline morphology with irregular
      topology was observed for its isomer (E)-1-(4-chlorophenyl)-2-(4
      (octyloxy)phenyl) diazene (compound 2).

PMID- 16649794
TI  - Rheology and phase behavior of poly(n-butyl acrylate)-block-poly(acrylic acid) in
      aqueous solution.
AB  - The surface activity and the rheological properties of aqueous solutions of the
      amphiphilic block copolymer poly(n-butyl acrylate)-block-poly(acrylic acid) (PnBA
      b-PAA) were studied as a function of the degree of neutralization, alpha, of the
      poly(acrylic acid) block. Although the block copolymer spontaneously forms
      spherical micelles having a stretched PAA corona and a collapsed PnBA core in
      water for alpha > 0.1, the solutions do not exhibit any surface activity at this
      degree of neutralization. Cryo-TEM micrographs show that the radii of the
      hydrophobic core of the largest micelles are as long as the length of the
      hydrophobic chain. The micelles, however, have a broad size distribution, and on
      average, as shown by SANS, the micelles are only about half as long. At
      concentrations as low as 1 wt %, the solutions exhibit highly viscoelastic
      behavior and have a yield stress value depending on alpha. The globular micelles
      are highly ordered in the bulk phase, and the viscoelastic properties are a
      result of the dense packing of the micelles. The addition of salt or cationic
      surfactants dramatically decreases the viscosity of the solution. The observed
      properties seem to be due to electrostatic interactions between the PAA chains of
      the micelles.

PMID- 16649795
TI  - Structural and diffusion characterizations of steam-stable mesostructured
      zeolitic UL-ZSM-5 materials.
AB  - A series of mesoporous UL-ZSM-5 materials (Si/Al = 50) with different micro- and
      mesoporosity as well as crystallinity was prepared following the procedure
      proposed in one of our recent studies (Trong-On, D.; Kaliaguine, S. Angew. Chem.
      Int. Ed. 2001, 40, 3248-3251. Trong-On, D.; Kaliaguine, S. U.S. Patent 6,669,924,
      B1, 2003). These materials have zeolitic structure in the form of nanoparticles
      intergrown in the walls of the amorphous wormhole-like aluminosilicate mesopores
      of Al-Meso-50, which was used as a precursor in the synthesis. The structure,
      crystallinity, and textural properties of the synthesized materials, as well as a
      reference ZSM-5 zeolite sample, were determined by X-ray diffraction (XRD),
      transmission electron microscopy (TEM)/scanning electron microscoy (SEM)
      analyses, Fourier transform infrared spectroscopy (FTIR), 27Al magic angle
      spinning (MAS) nuclear magnetic resonance (NMR), and nitrogen
      adsorption/desorption techniques. The acid properties were examined by FTIR of
      adsorbed pyridine. UL-ZSM-5 materials were shown to be highly hydrothermally
      stable. The diffusion of two C7 hydrocarbons, i.e., n-heptane and toluene, in
      four UL-ZSM-5 materials with different microporosities, related acidities, and
      crystallinities were investigated using the zero-length column (ZLC) method.
      Furthermore, the wormhole-like mesostructured aluminosilicate precursor (Al-Meso
      50) and a reference MFI zeolite sample were also investigated using the same
      technique. A theoretical model considering a combination of mesopore diffusion
      (with surface slip in the main channels) with an activated, mainly surface
      diffusion mechanism in the intrawall biporous structure, was proposed and
      employed to interpret the experimental ZLC results. A classical Knudsen type of
      diffusion was replaced by an activated surface slip type of diffusion mechanism
      in the mesopores. The transport of n-heptane in UL-ZSM-5 materials was found to
      be mainly controlled by mesopore diffusion in the main-channel structure, while
      that of toluene was dominated by the intrawall diffusion process. Diffusion
      activation energies of n-heptane are about 2 times higher in comparison to
      toluene, which has a larger kinetic diameter. The main mesopore channel structure
      seems to appreciably contribute to the overall mass transport. Furthermore, the
      effect of hydrothermal treatment (20% steam at 800 degrees C for 24 h) on the
      diffusion of these two sorbates on UL-ZSM-5 materials was also evaluated.

PMID- 16649796
TI  - Characterization of active phosphorus surface sites at synthetic carbonate-free
      fluorapatite using single-pulse 1H, 31P, and 31P CP MAS NMR.
AB  - The chemically active phosphorus surface sites defined as PO(x), PO(x)H, and
      PO(x)H2, where x = 1, 2, or 3, and the bulk phosphorus groups of PO4(3-) at
      synthetic carbonate-free fluorapatite (Ca5(PO4)3F) have been studied by means of
      single-pulse 1H,31P, and 31P CP MAS NMR. The changes in composition and relative
      amounts of each surface species are evaluated as a function of pH. By combining
      spectra from single-pulse 1H and 31P MAS NMR and data from 31P CP MAS NMR
      experiments at varying contact times in the range 0.2-3.0 ms, it has been
      possible to distinguish between resonance lines in the NMR spectra originating
      from active surface sites and bulk phosphorus groups and also to assign the peaks
      in the NMR spectra to the specific phosphorus species. In the 31P CP MAS NMR
      experiments, the spinning frequency was set to 4.2 kHz; in the single-pulse 1H
      MAS NMR experiments, the spinning frequency was 10 kHz. The 31P CP MAS NMR
      spectrum of fluorapatite at pH 5.9 showed one dominating resonance line at 2.9
      ppm assigned to originate from PO4(3-) groups and two weaker shoulder peaks at
      5.4 and 0.8 ppm which were assigned to the unprotonated PO(x) (PO, PO2-, and
      PO3(2-)) and protonated PO(x)H (PO2H and PO3H-) surface sites. At pH 12.7, the
      intensity of the peak representing unprotonated PO(x) surface sites has increased
      1.7% relative to the bulk peak, while the intensity of the peaks of the
      protonated species PO(x)H have decreased 1.4% relative to the bulk peak. At pH
      3.5, a resonance peak at -4.5 ppm has appeared in the 31P CP MAS NMR spectrum
      assigned to the surface species PO(x)H2 (PO3H2). The results from the 1H MAS and
      31P CP MAS NMR measurements indicated that H+, OH-, and physisorbed H2O at the
      surface were released during the drying process at 200 degrees C.

PMID- 16649797
TI  - Ti-Si mixed oxides prepared by polymer in situ sol-gel chemistry with the aid of
      CO2.
AB  - A method to prepare titania-silica binary oxides is proposed in this work. In
      this route, inorganic precursors tetraethyl orthosilicate (TEOS) and titanium
      isopropoxide (TIP) were simultaneously or sequentially impregnated into a
      polypropylene (PP) matrix using supercritical carbon dioxide as a swelling agent
      and carrier. Hydrolysis and condensation reaction of the precursors confined in a
      polymer network were induced by treating the composites in 1 mol.dm(-3) (1 M)
      HCl. Then the PP matrix was decomposed at higher temperature, and titania-silica
      binary oxides were obtained. The mixed oxides were characterized by X-ray
      diffraction and Raman, FTIR, and X-ray photoelectron spectroscopy. It was
      demonstrated that the structure of the oxides depended strongly on the procedure
      to impregnate the precursors. The simultaneous method, in which the TEOS and TIP
      were simultaneously impregnated into a PP matrix, resulted in mixed oxides with
      highly dispersed titanium oxide species in the SiO2 matrix, while the sequential
      method produced the mixed oxide with separate SiO2 and TiO2 phases which were
      connected by Ti-O-Si bands at the interface. The method described in this work
      provides a new route to control the texture of TiO2-SiO2 mixed oxide simply by
      the impregnation sequence.

PMID- 16649798
TI  - Enhancing the photoluminescence intensity of conjugated polycationic polymers by
      using quantum dots as antiaggregation reagents.
AB  - The aggregation in conjugated polyelectrolytes (CPs) can be effectively reduced
      by the formation of CP/nanoparticle assemblies. The photophysical properties of
      various nanoassemblies were studied by means of UV-visible and fluorescence
      spectroscopy in solution and as thin films. The dissociation of the polymer
      chains is caused by favorable electrostatic interactions between the cationic
      substituents of the CPs and the anionic charges present on the surface of the
      nanoparticles. Such an efficient displacement of pi-stacking by competitive
      positive interactions constitutes the first example of positive aggregation
      modulation.

PMID- 16649799
TI  - Starch nanocrystals with large chain surface modifications.
AB  - Nanoscale monocrystalline starch particles were successfully modified using
      stearic acid chloride and poly(ethylene glycol) methyl ether. Surface
      modification was confirmed using FTIR, XPS spectroscopy, and contact angle
      measurements. X-ray diffraction and DSC analysis confirmed that there was no
      alteration of the starch crystalline structure due to the surface modification.
      The grafts at the starch surface were also found to crystallize on the surface.
      TEM showed the individualization of nanoparticles as a result of the reduction of
      polar and hydrogen bonding forces. These results show our ability to modify the
      starch nanocrystal surface with plasticizing chains. Modified nanoparticles can
      find applications as compatibilized polymer additives, surface-active particles,
      and co-continuous nanocomposite precursors.

PMID- 16649800
TI  - Synthesis, characterization, and interfacial properties of an oligomeric,
      cationic fluorooxetane.
AB  - The synthesis and characterization of a cationic oligo(fluorooxetane) surfactant
      with pendant -C4F9 groups are reported. Molecular area demand at saturation was
      determined to be 55.6 +/- 0.3 angstroms2/molecule and characteristic of an
      oligomer. The adsorption of the cationic oligo(fluorooxetane) to the air-water
      interface appears to be diffusion-limited, and dilational rheological properties
      of the adsorbed molecules are representative of a "soluble" monolayer. Adsorption
      dynamics have been measured yielding diffusion coefficients that are dependent on
      concentration and in the 10(-7)-10(-8) cm2/s range. Complex moduli from
      dilational interfacial rheological measurements as a function of oscillation
      frequency were well fitted to the Lucassen-van den Tempel equation, providing an
      estimate of the Gibbs elasticity. The combination of the oligomeric nature of the
      fluorosurfactant, short perfluoroalkyl chain and its interfacial properties
      suggests that this synthetic approach is an attractive route to the development
      of fluorinated surfactants that avoid the environmental concerns of small
      molecule, long perfluoroalkyl-chain surfactants.

PMID- 16649801
TI  - Motional heterogeneity of intercalated species in modified clays and poly(epsilon
      caprolactone)/clay nanocomposites.
AB  - Modified laponites and synthetic saponites are used as precursors for the
      preparation of poly(epsilon-caprolactone) (PCL)/clay nanocomposites. The
      structure and dynamics of species intercalated in the modified clays and the
      corresponding nanocomposites are characterized by X-ray diffraction and magic
      angle spinning NMR. The influence of the headgroup, the hydrocarbon chain length,
      and the loading of the surfactant on the nanocomposite formation are discussed.
      The yield of PCL intercalation is related to the probability of direct polymer
      clay interactions and to the size of the clay platelets. Relaxation times in the
      laboratory and rotating frames that allow characterization of fast and slow
      molecular dynamics in these systems are discussed, showing a motional
      heterogeneity of the intercalated species.

PMID- 16649802
TI  - Influence of microwave radiation on the growth of gold nanoparticles and
      microporous zincophosphates in a reverse micellar system.
AB  - The water core of reverse micelles has been extensively used as the site for
      synthesis of a variety of materials. However, water-in-oil reverse micelles have
      a limited range of temperatures over which they are stable as a single phase.
      Directing heat to the water cores, the usual site of synthesis without heating
      the bulk provides added opportunities for synthesis. Microwave radiation is a
      method for superheating the water cores. In this study, we use an H2O-sodium
      bis(2-ethylhexyl) sulfosuccinate (AOT)-heptane reverse micelle system for the
      synthesis of Au particles by hydrazine reduction of HAuCl4 in the presence and
      absence of microwave radiation. The duration of the microwave radiation was
      limited to a 2-min duration at a power of 300 W, thereby ensuring that the
      reverse micelle phase is maintained during the synthesis. At all hydrazine
      concentrations studied (0.5-2 M), the presence of microwave radiation led to an
      increase in the particle size of Au. The second system examined was the growth of
      microporous zincophosphate-X (ZnPO-X, an analogue of the faujasite structure)
      synthesized from H2O-dioctyldimethylammonium chloride (DODMAC)-heptane reverse
      micelle system. Microwave radiation was applied for 1 min at 150 W at various
      stages of the nucleation and growth process, and did not disrupt the reverse
      micelle system. Product analysis after 48 h of reaction showed that the 1-min
      microwave pulse, if applied during the nucleation stage (the first 4 h), promoted
      the formation of NaZnPO4.H2O over ZnPO-X. The effect of the microwave pulse at
      the growth stage was to promote the formation of ZnPO-X. Absorption of the
      microwave radiation by the water core and surrounding polar surfactant molecules
      leads to a rapid rise in local temperature (predicted to be approximately 150
      degrees C/min for the AOT system), increasing the rates of intramicellar
      reactions.

PMID- 16649803
TI  - Preparation of titania-coated polystyrene particles in mixed solvents by ammonia
      catalysis.
AB  - A mixed-solvent method was developed to coat polystyrene (PS) spheres with
      smooth, homogeneous shells of amorphous titania by ammonia catalysis. The TEM
      images showed that, in the presence of ammonia, the thickness of titania shells
      could be controlled in the range of 8-65 nm by varying the concentration of
      titanium tetrabutoxide (TBOT) in the ethanol/acetonitrile mixed solvents with an
      appropriate volume ratio. The diffusion-controlled mechanism of the mixed
      solvents and the catalysis mechanism of ammonia were investigated. After the
      calcination of core-shell particles for 2 h at 500 degrees C, spherical hollow
      titania shells could be obtained, and the surfaces of the particles remained
      quite smooth and homogeneous. The XRD analysis indicated that calcination
      promoted the transformation of amorphous titania into an anatase phase.

PMID- 16649804
TI  - Dendritic nanostructures of silver: facile synthesis, structural
      characterizations, and sensing applications.
AB  - Silver nanodendrites are synthesized by a simple surfactant-free method using a
      suspension of zinc microparticles as a heterogeneous reducing agent. Structural
      characterizations suggest the preferential growth along 100 and 111 directions by
      oriented attachment of silver nanocrystals in the diffusion limit, leading to the
      formation of silver nanodendrites 20-30 nm in stem and branch diameter and 5-50
      microm in length. Surface-enhanced Raman scattering studies show that the silver
      nanodentrites give an intensive and enhanced Raman scattering when pyridine was
      used as a probing molecule. We have also demonstrated that the silver
      nanodendrites increase the sensitivity of an electrochemical glucose biosensor by
      as much as 1-2 orders of magnitude.

PMID- 16649805
TI  - Evaluation of surface roughness of hydrogels by fractal texture analysis during
      swelling.
AB  - The surface of a biomaterial reacts in contact with biological fluids. Hydrogels
      are used to prepare biomaterials. The surface roughness of materials can be
      explored by several techniques. However, when considering hydrogels, the surface
      examined in the dry state does not reflect the final conformation. How the
      surface roughness is affected by swelling has been little explored by
      quantitative methods. We have evaluated the surface roughness of poly(2
      hydroxyethyl methacrylate) (i.e., pHEMA) by image analysis. Images of disks,
      prepared from linear pHEMA, were obtained on a light microscope after various
      incubation times in saline. Fractal texture analysis was done on images to
      determine the fractal dimension D. In this study, D exhibited a significant
      decrease during swelling and was highly correlated with the swelling ratio (r2 =
      0.994, p < 0.00001). Water uptake by the surface of the polymer affected the
      surface roughness. Image analysis using fractal algorithms appears to be the most
      interesting technique for the quantitative exploration of surfaces of hydrated
      materials that cannot be measured by conventional methods.

PMID- 16649806
TI  - Structural and mechanistic investigation of a phosphate-modified HZSM-5 catalyst
      for methanol conversion.
AB  - Phosphorus modification of a HZSM-5 (MFI) zeolite by wet impregnation has long
      been known to decrease aromatic formation in methanol conversion chemistry. We
      prepared and studied a catalyst modified by introducing trimethylphosphine under
      reaction conditions followed by oxidation. Magic-angle spinning (MAS) NMR shows
      that extensive dealumination occurs, resulting in a catalyst with a much higher
      framework SiO2/Al2O3 ratio, as well as extraframework aluminum and approximately
      1.4 equiv of entrained phosphoric acid (under working conditions) per aluminum.
      Upon dehydration or regeneration, the phosphoric acid is converted, reversibly,
      to entrained P4O10. The aromatic selectivity of the modified catalyst is
      significantly lower than that of an unmodified zeolite with a similar, increased
      framework SiO2/Al2O3 ratio. By comparing the rates of H/D exchange in propene
      under conditions similar to those in methanol conversion chemistry, we determined
      that the acid site strength is indistinguishable on modified and unmodified
      zeolites, and this is consistent with theoretical modeling. On the phosphorus
      modified zeolite, the rate of propene oligomerization is greatly suppressed,
      suggesting that entrained phosphate is an impediment to sterically demanding
      reactions.

PMID- 16649807
TI  - Simultaneous Alignment and Micropatterning of Organic Crystallites under a
      Modulated Magnetic Field.
AB  - In a previous paper, we reported the micropatterning of magnetically isotropic
      particles using a microscopically modulated magnetic field. In this paper, we
      report that the alignment occurs simultaneously if the particles have magnetic
      anisotropy. An oil-in-water emulsion of p-terphenyl or anthracene was subjected
      to the modulated magnetic field and allowed to evaporate the solvent to obtain a
      line pattern consisting of the crystallites with alignment. The patterned samples
      exhibited an emission strongly polarized in the direction of the applied magnetic
      field that is perpendicular to the patterning lines.

PMID- 16649808
TI  - Meta-linked poly(phenylene ethynylene) conjugated polyelectrolyte featuring a
      chiral side group: helical folding and guest binding.
AB  - A water soluble, meta-linked poly(phenylene ethynylene) featuring chiral and
      optically active side groups based on L-alanine (mPPE-Ala) has been studied by
      using absorption, fluorescence, and circular dichroism spectroscopy. Studies of
      mPPE-Ala in methanol/water solvent mixtures show that the polymer folds into a
      helical conformation, and the extent of helical folding increases with the volume
      % water in the solvent. The presence of the helical conformation is signaled by
      the appearance of a broad, excimer-like visible fluorescence band, combined with
      a strong bisignate circular dichroism signal in the region of the pi,pi
      absorption of the polymer backbone. The circular dichroism signal exhibits
      negative chirality, suggesting that the left-handed (M-form) of the helix is in
      enantiomeric excess. Binding of the metallointercalator [Ru(bpy)2(dppz)]2+ (where
      bpy = 2,2-bipyridine and dppz = dipyrido[3,2-a:2',3'-c]phenazine) with the
      helical polymer is accompanied by the appearance of the orange-red
      photoluminescence from the metal complex. This effect is directly analogous to
      that observed when [Ru(bpy)2(dppz)]2+ binds to DNA via intercalation, suggesting
      that the metal complex binds to mPPE-Ala by intercalating between the pi-stacked
      phenylene ethynylene residues. Cationic cyanine dyes also bind to the periphery
      of the helical polymer in a manner that is interpreted as "groove binding". A
      circular dichroism signal is observed that is believed to arise from exciton
      coupling within the chiral cyanine dye chromophore aggregate that is formed as
      the dye molecules are oriented by the helical mPPE-Ala "template".

PMID- 16649809
TI  - Size control and growth process of alkylamine-stabilized platinum nanocrystals: a
      comparison between the phase transfer and reverse micelles methods.
AB  - Alkylamine-stabilized platinum nanoparticles are synthesized either by the phase
      transfer method or in reverse micelles. The phase-transfer method produces
      nanocrystals that are quite spherical whereas the synthesis in reverse micelles
      generates a large number of wormlike structures. An alkylamine is used as a
      stabilizing agent to prevent nanoparticle coalescence, and it is shown that there
      is an inverse relationship between the alkylamine chain length and the platinum
      nanoparticle diameter. By comparing alkylamine and alkylthiol analogues, it is
      found that the integrity of the different crystallites depends on the strength of
      the interaction between the stabilizing agent and the platinum nanocrystals. The
      results obtained and the comparison made between the two synthesis methods
      improve the understanding of the growth mechanisms of platinum nanocrystals in
      disperse media.

PMID- 16649810
TI  - Characterization of mixed alcohol monolayers adsorbed onto a Au(111) electrode
      using electro-fluorescence microscopy.
AB  - A single-crystal Au(111) electrode modified with an adsorbed layer of 1
      octadecanol (C18OH) or oleyl alcohol (OLA) in pure or mixed composition was
      characterized using electrochemical and in situ fluorescence microscopy. Cyclic
      voltammetry and differential capacitance measurements revealed a repeatable,
      potential-induced adsorption/desorption process of the surfactant to/from the
      electrode surface while charge density and film pressure measurements indicated
      quasi-ideal mixing of the two adsorbed alcohols. A layer less defective than pure
      C18OH was created with incorporated OLA. Optical characterization was
      accomplished using epi-fluorescence microscopy combined with electrochemistry
      (electro-fluorescence microscopy) through the incorporation of two fluorescent
      probes into the adsorbed surfactant layer. Since molecular luminescence is
      quenched by a nearby metal, fluorescence was only observed when the fluorescent
      dye/alcohol layers were desorbed and therefore separated from the metal surface.
      When desorbed, the structure of the alcohol layers were similar in character,
      revealing aggregated features which did not change in morphology over numerous
      desorption/re-adsorption cycles. We have also used the electro-fluorescence
      technique to estimate the distance separating the metal and desorbed surfactant
      and believe that the molecules are displaced from the electrode surface by a
      distance not more than 40 nm.

PMID- 16649811
TI  - Electrochemical characterization of gold stepped surfaces modified with Pd.
AB  - Three different single crystals, Au(111), Au(332), and Au(331), were used as the
      substrate for palladium deposition in the underpotential deposition (UPD) regime.
      The Au(111) single crystal was used for control experiments to compare the
      behavior of the vicinal surfaces. Cyclic voltammetry in 0.1 M sulfuric acid
      solution, as well as electrochemical impedance spectroscopy (EIS) were used to
      study the hydrogen adsorption on the Pd thin films. Our results suggest that the
      voltammetric peaks at approximately 0.3 V versus the reversible hydrogen
      electrode (RHE) are related to the adsorption of hydrogen at large palladium
      terraces, and that at least two adjacent Pd rows are needed in order for the
      adsorption to take place. Further cycling to more positive potentials leads to
      the oxidation and slow dissolution of the Pd film. The behavior of the oxidation
      cycles is explained in terms of a higher stability of Pd at the steps.

PMID- 16649812
TI  - Caregiving: the greatest challenge.

PMID- 16649813
TI  - Sclerotic hands with fissuring and thickening of palms.

PMID- 16649814
TI  - Race and depression: does race affect the diagnosis and treatment of late-life
      depression?
AB  - While it is recognized that medical and neurological comorbidities complicate the
      accurate diagnosis and treatment of late-life depression, the possibility that
      patient race or even gender may affect management decisions is less discussed.
      This article reviews the current literature on racial differences in the
      diagnosis and treatment of late-life depression, including recent studies on
      physician contribution to disparities.

PMID- 16649815
TI  - Health promotion in older adults. Prescribing exercise for the frail and home
      bound.
AB  - Some degree of physical activity is always preferable to a sedentary lifestyle.
      For home bound elderly, with limited mobility and strength, physical activity
      should be focused on "functional fitness," such as performing activities of daily
      living, transfers, and mobility. We examine the benefits of exercise for frail
      home bound elderly, potential barriers to exercise, and ways to initiate a
      physical activity program.

PMID- 16649816
TI  - pH-dependent transitions in xanthorhodopsin.
AB  - Xanthorhodopsin (XR), the light-driven proton pump of the halophilic eubacterium
      Salinibacter ruber, exhibits substantial homology to bacteriorhodopsin (BR) of
      archaea and proteorhodopsin (PR) of marine bacteria, but unlike them contains a
      light-harvesting carotenoid antenna, salinixanthin, as well as retinal. We report
      here the pH-dependent properties of XR. The pKa of the retinal Schiff base is as
      high as in BR, i.e. > or =12.4. Deprotonation of the Schiff base and the ensuing
      alkaline denaturation cause large changes in the absorption bands of the
      carotenoid antenna, which lose intensity and become broader, making the spectrum
      similar to that of salinixanthin not bound to XR. A small redshift of the retinal
      chromophore band and increase of its extinction, as well as the pH-dependent
      amplitude of the M intermediate indicate that in detergent-solubilized XR the pKa
      of the Schiff base counterion and proton acceptor is about 6 (compared to 2.6 in
      BR, and 7.5 in PR). The protonation of the counterion is accompanied by a small
      blueshift of the carotenoid absorption bands. The pigment is stable in the dark
      upon acidification to pH 2. At pH < 2 a transition to a blueshifted species
      absorbing around 440 nm occurs, accompanied by loss of resolution of the
      carotenoid absorption bands. At pH < 3 illumination of XR with continuous light
      causes accumulation of long-lived photoproduct(s) with an absorption maximum
      around 400 nm. The photocycle of XR was examined between pH 4 and 10 in
      solubilized samples. The pH dependence of recovery of the initial state slows at
      both acid and alkaline pH, with pKas of 6.0 and 9.3. The decrease in the rates
      with pKa 6.0 is apparently caused by protonation of the counterion and proton
      acceptor, and that at high pH reflects the pKa of the internal proton donor,
      Glu94, at the times in the photocycle when this group equilibrates with the bulk.

PMID- 16649818
TI  - Neural correlates of the affect regulation model in schizophrenia patients with
      substance use history: a functional magnetic resonance imaging study.
AB  - BACKGROUND: The lifetime prevalence of substance use disorders among
      schizophrenia patients is close to 50%. The negative consequences of substance
      abuse in schizophrenia are well documented, but the etiology of this comorbid
      condition remains unknown. According to the affect regulation model,
      schizophrenia patients abuse drugs in order to cope with their negative affects.
      Supporting the model, clinical studies have shown that dual-diagnosis patients
      have less blunting of affect and that they experience more negative affect. We
      hypothesized that patients with a history of substance use would have increased
      cerebral activations in response to aversive stimuli when compared to abstinent
      patients. METHOD: Schizophrenia patients were divided into 2 groups: patients
      with (SCZ-SU group; N = 12) and without (SCZ group; N = 11) a current or past
      substance use disorder (alcohol, cannabis, and/or LSD). Diagnoses were made
      according to DSM-IV criteria. Using functional magnetic resonance imaging (fMRI),
      patients were scanned during passive viewing of emotionally negative pictures
      (International Affective Picture System). Data were gathered from September 2001
      to December 2003. RESULTS: Subjectively, the emotional experience induced by
      viewing the negative pictures was rated significantly higher in the SCZ-SU group
      than in the SCZ group (p = .008). Neurally, in the SCZ-SU group, significant loci
      of activation were identified in the right medial prefrontal cortex (Brodmann's
      area [BA] 10), left medial prefrontal cortex (BA 10), right orbitofrontal cortex
      (BA 47), and left amygdala. No significant loci of activation were observed in
      the SCZ group. CONCLUSIONS: These results suggest that the functioning of the
      medial prefrontal cortex, thought to be impaired in patients with prominent
      negative symptoms, is more preserved in dual-diagnosis schizophrenia. This
      relative preservation could be primary or secondary to substance use.

PMID- 16649819
TI  - Association between attention-deficit/hyperactivity disorder and bulimia nervosa:
      analysis of 4 case-control studies.
AB  - BACKGROUND: Impulsivity is a common feature of attention-deficit/hyperactivity
      disorder (ADHD), and evidence suggests that impulsivity traits may be an
      indicator of poor prognosis for individuals with bulimia nervosa. To identify
      whether there is an association between ADHD and bulimia nervosa, the authors
      systematically examined data from children and adults with and without ADHD.
      METHOD: We systematically identified rates of bulimia nervosa in individuals with
      and without ADHD (DSM-III-R criteria) in our 2 large pediatric and 2 large adult
      samples (N = 522 children, 742 adults). Subjects were assessed from the late
      1980s to February 1999. RESULTS: In the 2 samples of adults with and without
      ADHD, significantly greater rates of bulimia nervosa were identified in women
      with versus without ADHD (12% vs. 3%, p < .05 for 1 sample and 11% vs. 1%, p <
      .05 for the other sample). No significant differences in rates of bulimia nervosa
      were identified in men or children with ADHD when compared to sex-matched control
      subjects. CONCLUSION: Although preliminary and requiring further confirmation,
      these findings suggest that ADHD may be associated with bulimia nervosa in some
      women. If confirmed, this association between bulimia nervosa and ADHD could have
      important clinical and therapeutic implications.

PMID- 16649820
TI  - Quetiapine in the treatment of anxiety in patients with bipolar I or II
      depression: a secondary analysis from a randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: Quetiapine monotherapy shows efficacy in bipolar depression. The
      analyses in this multicenter, double-blind, randomized, fixed-dose, placebo
      controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms
      in bipolar depression. METHOD: Of 542 outpatients randomly assigned to treatment,
      539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a
      major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600
      or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety
      assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant
      items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton
      Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups
      versus placebo. RESULTS: At week 8, quetiapine 600 and 300 mg/day each
      demonstrated significant improvements in HAM-A total score versus placebo (-10.8
      and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved
      HAM-A total score from week 1. In bipolar I depression, quetiapine showed
      significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p <
      .001). In bipolar I depression, quetiapine also showed significant improvements
      versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and
      somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all
      p < .001), but not the HAM-D somatic anxiety item. In bipolar II depression,
      quetiapine reduced the HAM-A total score more than placebo, but the difference
      was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II
      depression, quetiapine showed significant improvement versus placebo on the HAM-A
      anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01).
      CONCLUSION: Quetiapine monotherapy shows efficacy in treating anxiety symptoms in
      bipolar I depression; however, the anxiolytic effects in bipolar II disorder
      require further investigation.

PMID- 16649821
TI  - The epidemiology of DSM-IV panic disorder and agoraphobia in the United States:
      results from the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: To present nationally representative data on the prevalence,
      correlates, and comorbidity of DSM-IV panic disorder (PAN), including the
      differentiation between panic with agoraphobia (PDA) and without agoraphobia
      (PDWA) and agoraphobia without a history of panic disorder (AG). METHOD: The data
      were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and
      Related Conditions (N = 43,093). Prevalence, correlates, and comorbidity of PAN,
      PDA, and PDWA with Axis I and II disorders were determined. RESULTS: Prevalences
      of 12-month and lifetime PAN were 2.1% and 5.1%. Rates of 12-month and lifetime
      PDWA were 1.6% and 4.0%, exceeding those of 12-month (0.6%) and lifetime (1.1%)
      PDA. Rates of 12-month and lifetime AG were extremely low, 0.05% and 0.17%. Being
      female, Native American, middle-aged, widowed/ separated/divorced, and of low
      income increased risk, while being Asian, Hispanic, or black decreased risk for
      PAN, PDA, and PDWA. Individuals with PDA were more likely to seek treatment and
      had earlier ages at onset and first treatment, longer episodes, and more severe
      disability, impairment, panic symptomatology, and Axis I and II comorbidity than
      those with PDWA. CONCLUSION: PDA may be a more severe variant of PAN.
      Overrepresentation of PDA in treatment settings reflects increased treatment
      seeking and the severity of PDA relative to PDWA. The very low prevalence of AG
      leaves open questions about the meaning of the disorder as a distinct clinical
      entity as defined in the DSM-IV.

PMID- 16649822
TI  - A pilot study on differences in aggression in New York City and Madrid, Spain,
      and their possible impact on suicidal behavior.
AB  - OBJECTIVE: Published results from a U.S. study of depressed suicide attempters
      and a Madrid, Spain, study including all consecutively admitted suicide
      attempters suggested that aggression scores were higher in U.S. attempters. This
      observation led us to compare depressed attempters and controls from both suicide
      research centers and explore whether New York City (NYC) patients carry out
      suicidal acts of greater lethality than patients in Madrid. The study goals were
      (1) to compare aggression scores in attempters and healthy volunteers between the
      2 cities and (2) to determine whether higher aggression scores are associated
      with greater medical lethality of suicide attempts. METHOD: The respective
      samples from NYC and Madrid included attempters with a DSM-IV diagnosis of major
      depressive disorder (N = 117 and N = 133) and healthy controls (N = 90 and N =
      317). Aggression scores, measured by the Brown-Goodwin Scale, in attempters and
      healthy volunteers from both sites were compared using an analysis of variance
      model. The relationship between lethality of suicidal acts and aggression scores
      in attempters was assessed using logistic regression analyses. NYC subjects were
      recruited from 1998 to 2001, and Madrid subjects were selected from consecutive
      admissions in 1999. RESULTS: Depressed suicide attempters from NYC made attempts
      of greater lethality and reported more lifetime aggressive behavior than
      depressed attempters in Madrid. NYC healthy volunteers also reported more
      aggression than their Madrid counterparts. CONCLUSIONS: This pilot study suggests
      that the greater lethality of suicidal behavior in NYC compared to Madrid is
      related to higher aggression levels, although the data have limitations. Cross
      cultural studies are needed to verify whether aggression and higher lethality
      suicide attempts share a common diathesis explaining the higher suicide rates in
      NYC.

PMID- 16649823
TI  - An open-label trial of risperidone augmentation for refractory anxiety disorders.
AB  - BACKGROUND: There is a paucity of data to support "next-step" treatments for the
      many patients with anxiety disorders who remain symptomatic after initial
      pharmacotherapy. METHOD: Thirty patients with a primary diagnosis of an anxiety
      disorder-panic disorder (PD), social anxiety disorder (SAD), or generalized
      anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate (or
      maximally tolerated) antidepressant and/or benzodiazepine trial of at least 8
      weeks' duration prior to study initiation received open-label augmentation with
      flexibly dosed risperidone for 8 weeks. Participants were diagnosed using the
      Structured Clinical Interview for DSM-IV. RESULTS: Risperidone augmentation at a
      mean +/- SD dose of 1.12 +/- 0.68 mg/day (range, 0.25-3.00 mg/day) resulted in a
      significant reduction in anxiety symptoms across disorders as measured by the
      Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale
      for Anxiety (HAM-A) scores and for each disorder-specific primary outcome measure
      the Panic Disorder Severity Scale, the Liebowitz Social Anxiety Scale, and HAM-A
      in the intent-to-treat sample. Seventy percent (21/30) of participants completed
      the 8-week trial, with premature discontinuation due primarily to sedation and
      weight gain. CONCLUSIONS: Although conclusions are limited by the open-label,
      relatively brief nature of this trial, our data suggest that augmentation with
      low-dose risperidone may be a useful option for patients with PD, SAD, or GAD
      refractory to adequate initial intervention with antidepressants and/or
      benzodiazepines. Longer-term, controlled safety and efficacy data are needed to
      understand the place of risperidone augmentation in the algorithm of treatment
      options for refractory anxiety disorders.

PMID- 16649824
TI  - Use of treatment services and pharmacotherapy for bipolar disorder in a general
      population-based mental health survey.
AB  - OBJECTIVE: This study examined characteristics of treatment utilization in a
      large general population-based sample of bipolar subjects. METHOD: Data source
      was the Canadian Community Health Survey-Mental Health and Well-Being, a
      nationally representative, community mental health survey of over 36,000
      individuals conducted from May to December 2002. Subjects who met study criteria
      for a current or past manic episode were classified as having bipolar disorder.
      Sociodemographic and illness-related factors influencing likelihood of accessing
      treatment, delay to contact with treatment services, and use of pharmacotherapy
      among bipolar subjects were determined. RESULTS: Among the 852 bipolar subjects,
      45.2% had never accessed treatment services. Male gender (p = .001), lower level
      of education (p = .003), and immigrant status (p < .001) were each significantly
      negatively correlated with use of treatment services. Mean delay from illness
      onset to contact with any treatment services was 3.1 years. Sixty-six percent of
      bipolar subjects had not taken a mood stabilizer or antidepressant medication in
      the past year, and 22% used antidepressants without a mood stabilizer. Female
      bipolar subjects were significantly more likely than male subjects to be
      prescribed an antidepressant medication (OR = 1.99, p = .01), even in the absence
      of higher frequency of recent depressions. CONCLUSION: Many individuals with
      bipolar disorder never receive any form of mental health treatment, and, among
      those that do, use of pharmacotherapy is not consistent with guideline-based
      recommendations. These findings reinforce the importance of continued efforts to
      better identify bipolar individuals early in their course of illness, and the
      need for further educational focus on bipolar disorder for all mental health
      treatment providers.

PMID- 16649825
TI  - Persistent posttraumatic stress disorder following September 11 in patients with
      bipolar disorder.
AB  - OBJECTIVE: We examined the development of posttraumatic stress disorder (PTSD)
      following indirect exposure to the September 11, 2001, terrorist attacks in a
      cohort at high risk for adverse trauma-related sequelae as a result of having
      bipolar disorder. METHOD: Subjects (N = 137) were participants in the ongoing,
      naturalistic, longitudinal study Systematic Treatment Enhancement Program for
      Bipolar Disorder (STEP-BD) prior to September 11, 2001. The present study
      examined prospectively collected pre-event information about bipolar disorder and
      other potential predictors of PTSD, along with assessment of the level of
      indirect trauma exposure (i.e., via media) and peritraumatic distress in the
      aftermath of September 11, and their association with 9/11-related, new-onset
      PTSD as assessed by a self-report measure, the Posttraumatic Stress Diagnostic
      Scale. RESULTS: Posttrauma assessments were completed a mean +/- SD of 430.6 +/-
      78.7 days (range, 0.5-1.5 years) after September 11. Twenty percent (N = 27) of
      patients reported development of new-onset PTSD in response to the September 11
      attacks. Rates of PTSD were significantly associated with the presence of a
      hypomanic, manic, or mixed mood state at the time of trauma (chi(2) = 4.25; p <
      .05); 62% of patients in these states developed PTSD. Mania/hypomania remained a
      significant predictor of PTSD in response to the September 11 attacks after
      controlling for peritraumatic exposure and distress variables, suggestive of a
      substantial increase in risk compared with those in recovery (OR = 17; 95% CI =
      2.6 to 115.6; p = .0034). CONCLUSIONS: Rates of persistent new-onset PTSD among
      bipolar patients were elevated in the aftermath of the September 11 attacks. Our
      findings suggest that the presence of a manic state may be the most critical risk
      factor for adverse sequelae following indirect traumatic exposure in bipolar
      individuals.

PMID- 16649826
TI  - The effect of dermatologic precautions on the incidence of rash with addition of
      lamotrigine in the treatment of bipolar I disorder: a randomized trial.
AB  - OBJECTIVE: Prescribing recommendations specify that lamotrigine should ordinarily
      be discontinued at the first sign of rash, regardless of its type and severity,
      unless the rash is clearly not drug related. This practice helps to ensure that
      lamotrigine is discontinued in instances of serious rash (an event occurring in
      up to 0.13% of cases in bipolar clinical trials) but may lead to unnecessary
      discontinuation of lamotrigine for cases of nonserious rash arising from nondrug
      causes. Measures aimed at reducing overall occurrence of dermatologic reactions
      might reduce the incidence of nonserious rash leading to premature lamotrigine
      discontinuation. This study assessed the impact of specific instructions designed
      to decrease risk of dermatologic reactions, including nonserious rash, during
      initiation of and early treatment with lamotrigine in patients with bipolar I
      disorder. METHOD: Outpatients with DSM-IV-diagnosed bipolar I disorder >/= 13
      years of age at 188 sites were randomly assigned to receive Usual Care
      Precautions (UCP; precautions from the patient instructions in the prescribing
      information for reducing risk of rash including nonserious rash) or Dermatologic
      Precautions (DP; precautions as above [UCP] plus additional precautions intended
      to decrease risk of any dermatologic reaction including nonserious rash) during
      12 weeks of adding open-label lamotrigine to concomitant medications. Patients
      with comorbid medical and psychiatric problems were not excluded unless, in the
      opinion of the investigators, these problems were sufficiently severe to preclude
      participation. Investigators and patients were blinded to which precaution group
      patients were randomly assigned. The primary outcome measure was the rate of rash
      during the treatment period. Secondary outcome measures included clinical
      response to lamotrigine, assessed with the investigator- and self-rated Clinical
      Global Impressions-Bipolar version (CGI-BP) and the Clinical Global Impressions
      Efficacy Index (CGI-EI). Data were collected from August 2003 to August 2004.
      RESULTS: 867 (74%) of 1175 patients completed the study. Only 182 (15%) of 1175
      patients had an adverse event leading to discontinuation of study medication or
      withdrawal, including 62 (5.3%) of 1175 due to non-serious rash. No serious
      rashes were reported during the study in either group. The incidence of
      nonserious rash was similarly low in patients with UCP and DP (8.8% and 8.6%,
      respectively). CGI-BP-Severity and -Improvement scores indicated mood improvement
      when lamotrigine was added to existing therapy, and CGI-EI scores at weeks 5 and
      12 reflected a favorable balance between control of mood symptoms and
      tolerability. At both weeks 5 and 12, investigators reported that therapeutic
      effects of additional lamotrigine outweighed side effects in 74% of subjects.
      CONCLUSION: UCP and DP yielded low, similar non-serious rash rates, which were
      marginally lower than nonserious rash rates in prior clinical trials that did not
      utilize DP but marginally higher than that in a prior open case series using DP.
      Nevertheless, the results are encouraging: in this large study reflecting real
      world use, lamotrigine was well tolerated with no serious rash and low incidences
      of nonserious rash and discontinuation due to rash, and lamotrigine therapy was
      associated with clinical improvement in a heterogeneous cohort of patients with
      bipolar I disorder.

PMID- 16649827
TI  - Selective serotonin reuptake inhibitors in autism: a review of efficacy and
      tolerability.
AB  - BACKGROUND: Awareness of the impact and prevalence of autism spectrum disorders
      has significantly increased in recent years. Given the dearth of reliable
      interventions, there is great interest in demonstrating efficacy of the various
      treatment options. A growing body of evidence links autism spectrum disorders to
      abnormalities in serotonin function, and the selective serotonin reuptake
      inhibitors (SSRIs) have been utilized to target various symptoms of the
      disorders. This article reviews the available data on the efficacy and
      tolerability of SSRIs in individuals with autism spectrum disorders. Objectives
      for future research in this area will also be suggested. DATA SOURCES AND STUDY
      SELECTION: The entire PubMed database including MEDLINE (1966-July 2005) was
      searched for English-language biomedical articles. Search terms included autism,
      autism spectrum disorder, citalopram, escitalopram, fluoxetine, fluvoxamine,
      paroxetine, pervasive developmental disorder, selective serotonin reuptake
      inhibitors, and sertraline. All clinical trials evaluating treatment outcomes
      associated with the use of SSRIs in managing symptoms of autism that were
      identified in the search were reviewed. All randomized controlled trials and open
      label trials were included in this review. Case reports and case series were
      excluded. DATA SYNTHESIS: We identified 3 randomized controlled trials and 10
      open-label trials or retrospective chart reviews on the use of SSRIs in autism
      and autism spectrum disorders. The SSRIs that have been studied in autism
      spectrum disorders are citalopram, escitalopram, fluoxetine, fluvoxamine, and
      sertraline. Most studies demonstrate significant improvement in global
      functioning and in symptoms associated with anxiety and repetitive behaviors.
      While side effects were generally considered to be mild, increased activation and
      agitation occurred in some subjects. CONCLUSIONS: Although SSRIs may demonstrate
      therapeutic benefit in autism spectrum disorders, methodological weaknesses of
      many of the clinical trials suggest the need for additional randomized controlled
      trials. Furthermore, given the increased awareness of the dangers associated with
      SSRI-induced activation and agitation, the presence of these side effects in the
      autistic population warrants closer attention to dosage, titration, and subject
      selection issues.

PMID- 16649828
TI  - Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of
      comorbidity.
AB  - OBJECTIVE: The objective of this study was to determine if measures of broad
      clinical psychopathology or neuropsychological performance could aid in the
      prediction of therapeutic response to the highly selective norepinephrine
      transporter inhibitor, atomoxetine, among adults with attention
      deficit/hyperactivity disorder (ADHD). METHOD: We analyzed data from 2 double
      blind, placebo-controlled, parallel design studies of adult patients (Study I, N
      = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral
      and advertising. Subjects were randomly assigned to 10 weeks of treatment with
      atomoxetine or placebo and were assessed with Conners' Adult ADHD Rating Scales
      (CAARS), the General Well-Being Schedule (GWB), the Sheehan Disability Scale, the
      Stroop Color-Word Test (SCWT), and the Structured Clinical Interview for DSM-IV
      (SCID) before and after treatment. RESULTS: Therapeutic improvement on
      atomoxetine as evidenced by reduced CAARS scores was reliably predicted by the
      presence of a lifetime comorbid diagnosis of depression or post-traumatic stress
      disorder at baseline, while improvement on subscales of the GWB and Sheehan
      Disability Scale were predicted by these and other SCID endorsements, such as
      alcohol and substance use, as well as demographics such as age and gender. In
      light of the exploratory nature of this work and the many comparisons that were
      examined in the corresponding regression models, these findings should be
      regarded as tentative pending replication and extension in another dataset.
      CONCLUSION: From these findings, we conclude that the variable responsiveness of
      individuals to atomoxetine cannot be largely accounted for by differences in
      broad-spectrum psychopathology or neuropsychological indicators of attentional
      capacity.

PMID- 16649829
TI  - Effect of mirtazapine treatment on body composition and metabolism.
AB  - OBJECTIVE: Weight gain is a common side effect of psychotropic medications.
      Mirtazapine, a widely used antidepressant, induces adverse metabolic effects such
      as an increase in body weight. The aim of this study was to investigate the
      influence of mirtazapine treatment on body weight, body fat mass, glucose
      metabolism, lipoprotein profile, and leptin and its soluble receptor in a
      prospective, controlled study design. METHOD: Seven women who met the ICD-10
      diagnostic criteria for a depressive episode (ICD-10: F31-F33) were assigned to
      monotherapy with mirtazapine and observed for a 6-week period. Seven mentally and
      physically healthy female volunteers matched for age and body weight served as a
      control group. Data were collected from November 2002 to December 2003. RESULTS:
      The mean +/- SD body weight increased from 63.6 +/- 13.1 kg to 66.6 +/- 11.9 kg
      during mirtazapine treatment (p = .027). Fat mass increased in study subjects
      from 20.9 +/- 9.6 kg to 22.1 +/- 9.3 kg (p = .018). Insulin, glucose, and the
      homeostasis model assessment (HOMA) index for insulin resistance and lipid
      parameters remained stable. Leptin concentrations increased from 23.0 +/- 17.1
      ng/mL to 40.9 +/- 27.2 ng/mL (p = .018), whereas the soluble leptin receptor
      concentrations remained stable during mirtazapine treatment. In the control
      subjects, the investigated parameters remained stable. Between-group analyses of
      change scores revealed significant differences for body weight (p = .010), body
      mass index (p = .013), fat mass (p = .035), and leptin (p = .013). CONCLUSION:
      The antidepressant therapy with mirtazapine was associated with a significant
      increase in body weight, body fat mass, and leptin concentration. In contrast to
      other psychotropic medications inducing weight gain, such as some second
      generation antipsychotics, mirtazapine treatment did not influence the glucose
      homeostasis.

PMID- 16649830
TI  - Sociodemographic characteristics and cardiovascular risk factors in patients with
      severe mental disorders compared with the general population.
AB  - OBJECTIVE: To study the prevalence and distribution of cardiovascular risk
      factors in a group of patients with severe mental disorders compared with the
      general population and investigate if differences in sociodemographic background
      variables between groups were associated with differences in risk profile.
      METHOD: We compared data from the ongoing Ulleval 600 Study (205
      pharmacologically stable outpatients with DSM-IV psychotic disorders) with data
      from the 2000-2001 Oslo Health Study (18,770 individuals from the general
      population of the same area). Subjects were stratified according to age and
      gender and compared for ethnic background, level of education, marital status,
      and prevalence of risk factors. RESULTS: Patients had an overall prevalence of
      smoking, obesity, hypertension, dyslipidemia, and diabetes mellitus about twice
      that of the reference group. Patients aged 18 through 50 years had the highest
      level of risk factors when compared with the general population. There was no
      major difference in ethnic background or educational level between cohorts.
      CONCLUSION: The increased cardiovascular risk profile in patients is particularly
      pronounced in young individuals and could not be explained by sociodemographic
      variables alone.

PMID- 16649831
TI  - Distinguishing bipolar major depression from unipolar major depression with the
      screening assessment of depression-polarity (SAD-P).
AB  - BACKGROUND: Patients with bipolar I or II major depression are often misdiagnosed
      with unipolar major depression. The goal of this study was to develop and
      validate a brief instrument to screen for bipolar disorder in patients actively
      ill with major depression. METHOD: The sample consisted of subjects who enrolled
      in the National Institute of Mental Health-Collaborative Program on the
      Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode
      of major depression and included 91 subjects with bipolar I major depression, 52
      with bipolar II major depression, and 338 with unipolar major depression
      diagnosed according to Research Diagnostic Criteria. Most of the subjects were
      inpatients at the time of enrollment, and subjects were prospectively followed
      for up to 20 years. In order to create, test, and cross-validate the screening
      instrument, a split-sample data analytic procedure was performed. This procedure
      yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross
      validation sample, and the bipolar II cross-validation sample. Each group
      included subjects with bipolar major depression and subjects with unipolar major
      depression. Within the bipolar I index sample, subjects with bipolar I major
      depression at study intake were compared with subjects with unipolar major
      depression at study intake on a pool of 59 sociodemographic and clinical
      candidate variables. The 3 variables showing the greatest disparity between
      bipolar I subjects and unipolar subjects were selected for the screen, the
      Screening Assessment of Depression-Polarity (SAD-P). The operating
      characteristics of the SAD-P were then examined within the bipolar I index
      sample, bipolar I cross-validation sample, and bipolar II cross-validation
      sample. RESULTS: The items selected for the screening instrument were (1)
      presence of delusions during the current episode of major depression, (2) number
      of prior episodes of major depression, and (3) family history of major depression
      or mania. The screen identified bipolar major depression with a sensitivity of
      0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation
      sample, and 0.58 in the bipolar II cross-validation sample. With regard to
      misclassifying subjects with unipolar major depression, the screen provided a
      positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the
      bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation
      sample. CONCLUSION: We suggest using the 3-item SAD-P as a preliminary screen for
      bipolar disorder in patients who present with an active episode of major
      depression.

PMID- 16649832
TI  - Psychoeducation and compliance in the treatment of schizophrenia: results of the
      Munich Psychosis Information Project Study.
AB  - OBJECTIVE: The present study examined whether psychoeducational groups for
      patients with schizophrenic disorders and for their families can reduce
      rehospitalization rates and improve compliance. METHOD: 236 inpatients who met
      DSM-III-R criteria for schizophrenia or schizoaffective disorder and who had
      regular contact with at least 1 relative or other key person were randomly
      assigned to 1 of 2 treatment conditions. In the intervention condition, patients
      and their relatives were encouraged to attend psychoeducational groups over a
      period of 4 to 5 months. The patients' and relatives' psychoeducational programs
      were separate, and each consisted of 8 sessions. Patients in the other treatment
      condition received routine care. Outcomes were compared over 12-month and 24
      month follow-up periods. The study was conducted from 1990 to 1994. RESULTS: It
      was possible to significantly reduce the rehospitalization rate after 12 and 24
      months in patients who attended psychoeducational groups compared with those
      receiving routine care (p < .05). Patients who attended psychoeducational groups
      showed better compliance than patients under routine care without psycho
      education. CONCLUSIONS: The results suggest that a relatively brief intervention
      of 8 psychoeducational sessions with systematic family involvement in
      simultaneous groups can considerably improve the treatment of schizophrenia.
      Psychoeducation should be routinely offered to all patients with schizophrenia
      and their families.

PMID- 16649833
TI  - Medication adherence and long-term functional outcomes in the treatment of
      schizophrenia in usual care.
AB  - BACKGROUND: Relatively little is known about the relationships between medication
      adherence and long-term functional outcomes in the treatment of schizophrenia. To
      extend previous research, we prospectively examined the relationships between
      adherence with any antipsychotic medication and functional outcomes among
      schizophrenia patients treated over a 3-year period, assessed the stability of
      adherence over time, and examined whether adherence in the first year predicts
      changes in functional outcomes over the following 2 years. METHOD: Analyses
      included 1906 participants with DSM-IV diagnoses of schizophrenia or
      schizoaffective or schizophreniform disorder in a multi-site, 3-year,
      prospective, naturalistic study conducted in the United States between July 1997
      and September 2003. Outcome measures were assessed at 6-month intervals using
      systematic medical record abstraction and structured interview of patients.
      Adherence with antipsychotic regimen was assessed using patient-reported
      adherence and the medication possession ratio (percent days with prescription for
      any antipsychotic), dichotomized into adherence and non-adherence. Analyses
      employed generalized estimating equations and mixed models with repeated
      measures. RESULTS: Nonadherence was associated with poorer functional outcomes,
      including greater risks of psychiatric hospitalizations, use of emergency
      psychiatric services, arrests, violence, victimizations, poorer mental
      functioning, poorer life satisfaction, greater substance use, and more alcohol
      related problems (all p < .001). Adherence was relatively stable, with 77.3% of
      patients maintaining the same adherence status from the first year to the second
      year. Nonadherence in the first year predicted significantly poorer outcomes in
      the following 2 years. CONCLUSIONS: Findings highlight the importance of
      adherence with antipsychotic medication in the long-term treatment of
      schizophrenia and its potential beneficial impact on the mental health and
      criminal justice delivery systems.

PMID- 16649834
TI  - The effects of long-term clozapine add-on therapy on the rehospitalization rate
      and the mood polarity patterns in bipolar disorders.
AB  - OBJECTIVE: We investigated the effect long-term clozapine add-on therapy has on
      rehospitalization rate and mood polarity patterns in patients with bipolar
      disorders. METHOD: Clinical data from medical records of 51 patients with bipolar
      disorder (DSM-IV) treated with clozapine add-on for more than 6 months at the
      Refractory Bipolar Disorders Clinic of Seoul National University Hospital were
      retrospectively analyzed. Patients had been registered from 1995 to 2004.
      Rehospitalization rates were compared before and after clozapine add-on. The
      clinical polarity of episodes resulting in hospitalizations was also compared.
      Twenty-seven bipolar patients treated with clozapine add-on for more than 3 years
      were further analyzed for long-term stability. RESULTS: The number of hospital
      days per year was reduced in 90.2% of patients after clozapine add-on. Total
      number and duration of hospitalizations per year decreased, and the effect size
      of clozapine add-on was substantially large (Wilcoxon z = -5.48, p < .01 for
      number of hospitalizations/year; Wilcoxon z = -5.32, p < .01 for hospital
      days/year; r = -0.54 and -0.53, respectively). Significant reductions were found
      in the number and duration of hospitalizations associated with manic, depressive,
      and hypomanic episodes. Number and duration of hospitalizations associated with
      mixed episodes did not show significant changes. The long-term efficacy of
      clozapine add-on was supported by continuous reduction in hospital days per year
      in the 27 selected patients. CONCLUSION: Long-term clozapine add-on therapy was
      effective in reducing the number and duration of rehospitalizations of bipolar
      patients resistant to conventional treatment. A significant reduction was found
      in rehospitalizations associated with manic, depressive, and hypomanic episodes,
      whereas mixed episode-associated rehospitalizations did not show significant
      changes.

PMID- 16649835
TI  - Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment.
AB  - BACKGROUND: Anxiety disorders are common in later life, but little is known about
      the long-term benefits and risks of pharmacotherapy. METHOD: 30 patients aged 60
      years and older, with a DSM-IV anxiety disorder, entered a 32-week trial of
      citalopram. Data gathered at baseline and follow-up included anxiety symptoms
      using Hamilton Rating Scale for Anxiety (HAM-A) scores, quality of life using the
      Medical Outcomes Study 36-item Short Form (SF-36), and sleep using the Pittsburgh
      Sleep Quality Index (PSQI). Data analysis consisted of mixed-effect repeated
      measures models of HAM-A scores and pre-post comparison of SF-36 and PSQI scores.
      RESULTS: 30 persons entered treatment; most (27/30) had a primary DSM-IV
      diagnosis of generalized anxiety disorder (2 had panic disorder; 1 had
      posttraumatic stress disorder). Three subjects discontinued study medication due
      to side effects, 5 were terminated because of nonresponse, and 5 dropped out of
      the study for other reasons; thus, 17 subjects (57%) completed 32 weeks of
      treatment. Subjects' HAM-A scores improved significantly, with continuing
      improvements up until about 20 weeks of treatment. On the basis of a criterion of
      reduction in HAM-A to < 10 during the trial, 60% (18/30) of subjects were
      responders. Those who completed the 32-week trial had significant improvements in
      sleep and quality of life-including social functioning, vitality, mental health,
      and role difficulties due to emotional problems. CONCLUSIONS: In this 32-week
      study of citalopram for elderly persons with anxiety disorders, 60% responded.
      Those who received a full course of treatment experience significant improvements
      in quality of life and sleep quality.

PMID- 16649836
TI  - A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive
      gabapentin for bipolar disorder.
AB  - OBJECTIVE: To conduct the first randomized, controlled trial assessing the
      prophylactic efficacy of gabapentin in bipolar disorder. METHOD: We conducted a 1
      year, double-blind, randomized, comparative, placebo-controlled, parallel-group,
      multicenter study. As this was a pure prophylactic trial, only euthymic bipolar I
      and II patients (DSM-IV) were randomly assigned in a 1:1 ratio to gabapentin (N =
      13) or placebo (N = 12) added to the current treatment (lithium, valproate,
      carbamazepine, or any combination but not antipsychotics or antidepressants).
      Subjects participated in the study for 12 months. The primary efficacy parameter
      was the Clinical Global Impressions scale for Bipolar Illness, Modified (CGI-BP
      M), which was assessed at all visits. Other assessments were the Young Mania
      Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Hamilton
      Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the
      systematic collection of reported adverse events. Data were collected from May
      1999 to February 2004. RESULTS: The change from baseline to month 12 in mean CGI
      BP-M scores between groups was statistically significant (p = .0046). Mean score
      change from baseline to endpoint in the gabapentin group was -2.1, and the mean
      score change in the placebo group was -0.6. No emerging manic or depressive
      symptoms were seen in either group as measured with the YMRS, HAM-D, HAM-A, and
      PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean score change
      at month 12 in the gabapentin group was 0.9, and the mean score change in the
      placebo group was 0.05 (p = .0267). Overall, gabapentin was well tolerated.
      CONCLUSION: This small, randomized clinical trial comparing the prophylactic
      efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute
      efficacy, treatment with gabapentin might provide some benefit on the long-term
      outcome of bipolar disorder.

PMID- 16649837
TI  - Review of the pharmacologic management of depression.

PMID- 16649838
TI  - Use of atypical antipsychotics: observations from clinical practice.

PMID- 16649839
TI  - Toxic catatonia secondary to azithromycin.

PMID- 16649840
TI  - 3-acetyl-7-oxo-dehydroepiandrosterone for healing treatment-resistant
      posttraumatic stress disorder in women: 5 case reports.

PMID- 16649841
TI  - Exacerbation of PTSD symptoms with use of duloxetine.

PMID- 16649843
TI  - Methodological issues in a study of long-term maintenance therapy with quetiapine
      versus haloperidol decanoate.

PMID- 16649845
TI  - Neuropathologic changes in Alzheimer's disease: potential targets for treatment.
AB  - The cognitive symptoms of Alzheimer's disease (AD) are believed to be caused not
      only by the loss of neurons in the cholinergic and glutamatergic neural systems
      but also by the irregular functioning of surviving neurons in these 2 systems.
      Aberrant cholinergic functioning in AD has been linked to deficits in the
      neurotransmitter acetylcholine, while AD-related abnormalities in glutamatergic
      signaling have been attributed to excitotoxicity caused by the persistent, low
      level stimulation of glutamatergic neurons via the chronic influx of Ca(2+) ions
      through the N-methyl-D-aspartate (NMDA) receptor calcium channel. Glutamatergic
      abnormalities in AD can be corrected to some extent by the NMDA receptor
      antagonist memantine, an agent whose therapeutic efficacy is believed to be
      related to its low to moderate level of affinity for the NMDA receptor calcium
      channel, a characteristic that allows memantine to prevent excessive
      glutamatergic stimulation while still permitting normal glutamate-mediated
      neurotransmission to take place. Although the mechanism underlying the chronic
      stimulation of glutamatergic neurons in AD has yet to be elucidated, one
      hypothesis is that the characteristic neuropathologic features of AD -- beta
      amyloid deposits and neurofibrillary tangles -- induce brain inflammation, which
      in turn impairs glutamatergic receptor function in such a way that the ability of
      these receptors to prevent the influx of Ca(2+) in the absence of an appropriate
      presynaptic signal is compromised. If this hypothesis is correct, and if it is
      correct that beta-amyloid deposits and neurofibrillary tangles arise long before
      the symptomatic onset of AD, then memantine, with its ability to alleviate
      glutamatergic receptor overstimulation, would be expected to provide therapeutic
      benefits beginning from the earliest stages of the disease.

PMID- 16649846
TI  - Navigating patients and caregivers through the course of Alzheimer's disease.
AB  - Alzheimer's disease (AD) prevalence rates in the United States are expected to
      triple over the next 50 years, a consequence of the overall aging of the U.S.
      population. Because of the profound and far-reaching impact of AD, this projected
      increase in prevalence is expected to pose a tremendous challenge. Alzheimer's
      disease results in the cognitive and functional deterioration of the affected
      patient, and behavioral disturbances frequently accompany the disease.
      Furthermore, because of its progressive and debilitating nature, AD takes a
      dramatic emotional, physical, and financial toll on the patient's primary
      caregiver. Nonetheless, despite the burden experienced by both patients and
      caregivers, strategies for minimizing the negative consequences of AD are well
      characterized. Central to the successful management of AD is the prompt and
      accurate diagnosis of the disease, with current guidelines calling for a 2-tiered
      approach in which patients first undergo screening using a brief cognitive
      assessment tool, followed by a comprehensive battery of physical, psychological,
      and neurologic tests if signs of possible cognitive impairment are evident upon
      screening. Once a conclusive diagnosis of AD has been made, the development of a
      disease management approach targeting the needs of the patient and his or her
      caregiver becomes a primary concern. Pharmacologic interventions may play an
      important role in such approaches, as agents such as cholinesterase inhibitors
      and the N-methyl-D-aspartate receptor antagonist memantine have been associated
      with favorable outcomes for patients and caregivers alike. However, in addition
      to the therapeutic benefits of these agents, associated side effects and
      potential drug-drug interactions must also factor into decisions regarding the
      pharmacologic treatment of AD.

PMID- 16649847
TI  - Contemporary issues in the treatment of Alzheimer's disease: tangible benefits of
      current therapies.
AB  - Because of the mild symptomatology associated with its earlier stages,
      Alzheimer's disease (AD) is most commonly diagnosed in an intermediate to late
      stage of progression. Patients with moderate to severe AD at diagnosis have
      already experienced appreciable losses in cognition and functioning. However,
      such patients may still benefit greatly from the use of antidementia agents such
      as cholines-terase inhibitors (ChEIs) and the N-methyl-D-aspartate (NMDA)
      receptor open-channel antagonist memantine. Monotherapy regimens involving a ChEI
      or memantine have been shown to slow the progression of cognitive symptoms in
      patients with moderate to severe AD, although memantine is currently the only
      agent approved for use in this setting. Furthermore, combination therapy
      involving memantine and a ChEI has been shown to yield increased cognitive
      benefits relative to ChEI monotherapy, a result that is believed to be
      attributable to the distinct therapeutic mechanisms associated with NMDA receptor
      open-channel antagonists and ChEIs. Nonetheless, recent findings indicate that
      the therapeutic effects of these antidementia agents are not limited to
      cognition. For example, emerging data highlight the efficacy of ChEIs and
      memantine, used either alone or in combination, in improving outcomes related to
      patient functioning and behavior, 2 domains that may have a great deal of
      significance for patients and caregivers. Furthermore, recent clinical trial data
      suggest that antidementia agents may significantly delay nursing home placement,
      a unique endpoint that can be tremendously distressing to patients with AD and
      their caregivers. Thus, it is clear that the ChEIs and memantine provide
      substantial benefits that extend across the spectrum of symptoms of AD, improving
      outcomes for those who are affected, either directly or indirectly, by this
      debilitating condition.

PMID- 16649848
TI  - The social stressors-counterproductive work behaviors link: are conflicts with
      supervisors and coworkers the same?
AB  - The differential impact of conflict with supervisors and coworkers on the target
      of counterproductive work behaviors (CWB) was investigated using multiple data
      sources. The mediating role of negative emotions was also tested using an emotion
      centered model of CWB. Data were obtained from 133 dyads (incumbents plus a
      coworker) of full-time working participants representing a variety of occupations
      at the University of South Florida. Participants in the incumbent role were asked
      to complete a questionnaire measuring demographics, conflict, negative emotions,
      and CWB. The coworker was asked to respond to a shorter questionnaire measuring
      conflict and CWB regarding the incumbent's job. Evidence for a differential
      relationship between conflict sources and the target of CWB was found. The
      emotion-centered model of voluntary work behavior received partial support.

PMID- 16649849
TI  - The moderating effect of employee hostility on the association of long-term
      elderly care unit's negative resident characteristics to employee stress and well
      being.
AB  - This study examined the moderating effect of employee hostility on the
      association of unit-level resident characteristics (depression and behavioral
      problems) to individual-level employee's resident-related stress and
      psychological well-being during 1-year follow-up study among 501 employees in
      elderly care. Our results showed that employee hostility was associated with
      decreased psychological well-being. In addition, hostility moderated the
      association between unit-level proportion of depressive residents and resident
      related stress experienced by the individual employees. Hostile employees
      reported increased resident-related stress irrespective of the proportion of
      depressed residents in the unit. Instead, nonhostile employees were sensitive to
      the depression in the unit. They reported low levels of stress when depression
      levels in the unit were low and increased stress when depression levels were
      high.

PMID- 16649850
TI  - Work-supportive family, family-supportive supervision, use of organizational
      benefits, and problem-focused coping: implications for work-family conflict and
      employee well-being.
AB  - Employees (n = 230) from multiple organizations and industries were involved in a
      study assessing how work-family conflict avoidance methods stemming from the
      family domain (emotional sustenance and instrumental assistance from the family),
      the work domain (family-supportive supervision, use of telework and flextime),
      and the individual (use of problem-focused coping) independently relate to
      different dimensions of work-family conflict and to employees' affective and
      physical well-being. Results suggest that support from one's family and one's
      supervisor and the use of problem-focused coping seem most promising in terms of
      avoiding work-family conflict and/or decreased well-being. Benefits associated
      with the use of flextime, however, are relatively less evident, and using
      telework may potentially increase the extent to which family time demands
      interfere with work responsibilities.

PMID- 16649851
TI  - Social-cognitive determinants of hoist usage among health care workers.
AB  - Injuries caused by unsafe manual handling of patients are a major source of ill
      health in health care workers. The present study evaluated the ability of 4
      classes of variable to predict use of a hoist when moving a heavily dependent
      patient. Variables examined were occupational role characteristics, such as hours
      of work and type of shift worked; biographics, including age and height; aspects
      of occupational context, such as number of hoists available and number of
      patients; and motivational variables specified by the theory of planned behavior
      (Ajzen, 1985) and protection motivation theory (Rogers, 1983). Regression
      analyses showed that background and social-cognitive variables were able to
      account for 59% of variance in intention to use a hoist and 41% of variance in
      use of the hoist assessed 6 weeks later. Height, hoist availability, coworker
      injunctive norm, perceived behavioral control, response cost, response benefits,
      and social and physical costs of not using the hoist each explained independent
      variance in motivation to use a hoist at work.

PMID- 16649852
TI  - Call centers as lean service environments: job-related strain and the mediating
      role of work design.
AB  - Call centers can be considered as lean service systems, with leanness being
      described in terms of both dialog scripting and performance monitoring. Using
      data from a sample of 823 call handlers from 36 call centers, these lean
      characteristics are examined in relation to the prediction of call handler job
      related strain. Moreover, the extent to which this relationship can be accounted
      for by work design characteristics are examined. Findings confirm that employees
      who experience greater dialog scripting and more intensive performance monitoring
      show higher levels of strain. These relationships are fully mediated by work
      design. These findings demonstrate the importance of considering the impact of
      lean working practices on employee health.

PMID- 16649853
TI  - Self-stereotyping in the context of multiple social identities.
AB  - This research examines self-stereotyping in the context of multiple social
      identities and shows that self-stereotyping is a function of stereotyped
      expectancies held in particular relationships. Participants reported how others
      evaluated their math and verbal ability and how they viewed their own ability
      when their gender or ethnicity was salient. Asian American women (Experiment 1)
      and European Americans (Experiment 2) exhibited knowledge of stereotyped social
      expectancies and corresponding self-stereotyping associated with their more
      salient identity. African Americans (Experiment 3) exhibited some knowledge of
      stereotyped social expectancies but no corresponding self-stereotyping.
      Correlational evidence and a 4th experiment suggest that self-stereotyping is
      mediated by the degree to which close others are perceived to endorse stereotypes
      as applicable to the self.

PMID- 16649854
TI  - What do I think you're doing? Action identification and mind attribution.
AB  - The authors examined how a perceiver's identification of a target person's
      actions co-varies with attributions of mind to the target. The authors found in
      Study 1 that the attribution of intentionality and cognition to a target was
      associated with identifying the target's action in terms of high-level effects
      rather than low-level details. In Study 2, both action identification and mind
      attribution were greater for a liked target, and in Study 3, they were reduced
      for a target suffering misfortune. In Study 4, it was again found that action
      identification and mind attribution were greater for a liked target, but like
      that for the self or a liked other, positive actions were identified at higher
      levels than negative actions, with the reverse being true for disliked others. In
      Study 5, the authors found that instructing participants to adopt the target's
      perspective did not affect mind attribution but did lead to higher level
      identifications of the target's actions.

PMID- 16649855
TI  - Understanding knowledge effects on attitude-behavior consistency: the role of
      relevance, complexity, and amount of knowledge.
AB  - The role of properties of attitude-relevant knowledge in attitude- behavior
      consistency was explored in 3 experiments. In Experiment 1, attitudes based on
      behaviorally relevant knowledge predicted behavior better than attitudes based on
      low-relevance knowledge, especially when people had time to deliberate.
      Relevance, complexity, and amount of knowledge were investigated in Experiment 2.
      It was found that complexity increased attitude- behavior consistency when
      knowledge was of low-behavioral relevance. Under high-behavioral relevance,
      attitudes predicted behavior well regardless of complexity. Amount of knowledge
      had no effect on attitude- behavior consistency. In Experiment 3, the findings of
      Experiment 2 were replicated, and the complexity effect was extended to behaviors
      of ambiguous relevance. Together, these experiments support an attitude inference
      perspective, which holds that under high deliberation conditions, people consider
      the behavioral relevance and dimensional complexity of knowledge underlying their
      attitudes before deciding to act on them.

PMID- 16649856
TI  - You focus on the forest when you're in charge of the trees: power priming and
      abstract information processing.
AB  - Elevated power increases the psychological distance one feels from others, and
      this distance, according to construal level theory, should lead to more abstract
      information processing. Thus, high power should be associated with more abstract
      thinking-focusing on primary aspects of stimuli and detecting patterns and
      structure to extract the gist, as well as categorizing stimuli at a higher level
      relative to low power. In 6 experiments involving both conceptual and perceptual
      tasks, priming high power led to more abstract processing than did priming low
      power, even when this led to worse performance. Experiment 7 revealed that in
      line with past neuropsychological research on abstract thinking, priming high
      power also led to greater relative right-hemispheric activation.

PMID- 16649857
TI  - On racial diversity and group decision making: identifying multiple effects of
      racial composition on jury deliberations.
AB  - This research examines the multiple effects of racial diversity on group decision
      making. Participants deliberated on the trial of a Black defendant as members of
      racially homogeneous or heterogeneous mock juries. Half of the groups were
      exposed to pretrial jury selection questions about racism and half were not.
      Deliberation analyses supported the prediction that diverse groups would exchange
      a wider range of information than all-White groups. This finding was not wholly
      attributable to the performance of Black participants, as Whites cited more case
      facts, made fewer errors, and were more amenable to discussion of racism when in
      diverse versus all-White groups. Even before discussion, Whites in diverse groups
      were more lenient toward the Black defendant, demonstrating that the effects of
      diversity do not occur solely through information exchange. The influence of jury
      selection questions extended previous findings that blatant racial issues at
      trial increase leniency toward a Black defendant.

PMID- 16649858
TI  - Dating couples' attachment styles and patterns of cortisol reactivity and
      recovery in response to a relationship conflict.
AB  - This study investigated theoretically predicted links between attachment style
      and a physiological indicator of stress, salivary cortisol levels, in 124
      heterosexual dating couples. Cortisol was assessed at 7 points before and after
      an experimental conflict negotiation task, creating a trajectory of stress
      reactivity and recovery for each participant. Growth modeling of cortisol data
      tested hypotheses that (a) insecurely attached individuals show patterns of
      greater physiological stress reactions to interpersonal conflict than do securely
      attached individuals and (b) people with insecurely attached partners show
      patterns of greater stress in reaction to relationship conflict than those with
      securely attached partners. Hypothesis 1 was supported, but men and women
      differed in the type of insecure attachment that predicted stress trajectories.
      Hypothesis 2 was supported for men, but not for women. The discussion emphasizes
      the role of gender role norms and partner characteristics in understanding
      connections between adult attachment and patterns of cortisol responses to
      interpersonal stress.

PMID- 16649859
TI  - Exploring the psychological underpinnings of the moral mandate effect: motivated
      reasoning, group differentiation, or anger?
AB  - When people have strong moral convictions about outcomes, their judgments of both
      outcome and procedural fairness become driven more by whether outcomes support or
      oppose their moral mandates than by whether procedures are proper or improper
      (the moral mandate effect). Two studies tested 3 explanations for the moral
      mandate effect. In particular, people with moral mandates may (a) have a greater
      motivation to seek out procedural flaws when outcomes fail to support their moral
      point of view (the motivated reasoning hypothesis), (b) be influenced by in-group
      distributive biases as a result of identifying with parties that share rather
      than oppose their moral point of view (the group differentiation hypothesis), or
      (c) react with anger when outcomes are inconsistent with their moral point of
      view, which, in turn, colors perceptions of both outcomes and procedures (the
      anger hypothesis). Results support the anger hypothesis.

PMID- 16649860
TI  - Groups perform better than the best individuals on letters-to-numbers problems:
      effects of group size.
AB  - Individuals and groups of 2, 3, 4, or 5 people solved 2 letters-to-numbers
      problems that required participants, on each trial, to identify the coding of 10
      letters to 10 numbers by proposing an equation in letters, receiving the answer
      in letters, proposing a hypothesis, and receiving feedback on the correctness of
      the hypothesis. Groups of 3, 4, and 5 people proposed more complex equations and
      had fewer trials to solution than the best of an equivalent number of
      individuals. Groups of 3, 4, and 5 people had fewer trials to solution than 2
      person groups but did not differ from each other. These results suggest that 3
      person groups are necessary and sufficient to perform better than the best
      individuals on highly intellective problems.

PMID- 16649861
TI  - Self-esteem and organization of valenced information about others: the "Jekyll
      and Hyde"-ing of relationship partners.
AB  - The authors theorize that individuals with high self-esteem functionally
      integrate positive and negative partner information in memory, whereas those low
      in self-esteem segregate such information. The authors obtained support for this
      view in 7 studies. In a first set, participants judged whether positive and
      negative traits presented in an alternating or nonalternating order applied to a
      partner. Low but not high self-esteem individuals were slowed by the alternating
      order when judging relationship partners (but not inanimate objects). In a 2nd
      set, participants answered questions tapping integrated thinking, self-esteem,
      and other attributes. Higher self-esteem was associated with more integrated
      thinking when other attributes were controlled. In a final study, anxiously
      attached individuals were more labile in rating their spouse over a 5-day period.

PMID- 16649862
TI  - The social-cognitive model of achievement motivation and the 2 x 2 achievement
      goal framework.
AB  - Two studies examined hypotheses drawn from a proposed modification of the social
      cognitive model of achievement motivation that centered on the 2 x 2 achievement
      goal framework. Implicit theories of ability were shown to be direct predictors
      of performance attainment and intrinsic motivation, and the goals of the 2 x 2
      framework were shown to account for these direct relations. Perceived competence
      was shown to be a direct predictor of achievement goals, not a moderator of
      relations implicit theory or achievement goal effects. The results highlight the
      utility of attending to the approach-avoidance distinction in conceptual models
      of achievement motivation and are fully in line with the hierarchical model of
      achievement motivation.

PMID- 16649863
TI  - How money buys happiness: genetic and environmental processes linking finances
      and life satisfaction.
AB  - Measures of wealth such as income and assets are commonly considered to be
      objective measures of environmental circumstances, making direct contributions to
      life satisfaction. Here, the authors explored the accuracy of this assumption.
      Using a nationwide sample of 719 twin pairs from the National Survey of Midlife
      Development in the United States, the authors first noted the relative
      independence of most perceptions about financial status from measures of actual
      wealth. They then demonstrated that perceived financial situation and control
      over life completely mediated the association between measures of actual wealth
      and life satisfaction. Finally, they showed that financial resources appeared to
      protect life satisfaction from environmental shocks. In addition, control
      appeared to act as a mechanism translating life circumstances into life
      satisfaction.

PMID- 16649864
TI  - The costs and benefits of writing, talking, and thinking about life's triumphs
      and defeats.
AB  - Three studies considered the consequences of writing, talking, and thinking about
      significant events. In Studies 1 and 2, students wrote, talked into a tape
      recorder, or thought privately about their worst (N = 96) or happiest experience
      (N = 111) for 15 min each during 3 consecutive days. In Study 3 (N = 112),
      students wrote or thought about their happiest day; half systematically analyzed,
      and half repetitively replayed this day. Well-being and health measures were
      administered before each study's manipulation and 4 weeks after. As predicted, in
      Study 1, participants who processed a negative experience through writing or
      talking reported improved life satisfaction and enhanced mental and physical
      health relative to those who thought about it. The reverse effect for life
      satisfaction was observed in Study 2, which focused on positive experiences.
      Study 3 examined possible mechanisms underlying these effects. Students who wrote
      about their happiest moments--especially when analyzing them--experienced reduced
      well-being and physical health relative to those who replayed these moments.
      Results are discussed in light of current understanding of the effects of
      processing life events.

PMID- 16649865
TI  - Exposure to terrorism, stress-related mental health symptoms, and defensive
      coping among Jews and Arabs in Israel.
AB  - The authors conducted a large-scale study of terrorism in Israel via telephone
      surveys in September 2003 with 905 adult Jewish and Palestinian citizens of
      Israel (PCIs). Structural equation path modeling indicated that exposure to
      terrorism was significantly related to greater loss and gain of psychosocial
      resources and to greater posttraumatic stress disorder (PTSD) and depressive
      symptoms. Psychosocial resource loss and gain associated with terrorism were, in
      turn, significantly related to both greater PTSD and depressive symptoms. PCIs
      had significantly higher levels of PTSD and depressive symptoms than Jews.
      Further, PTSD symptoms in particular were related to greater authoritarian
      beliefs and ethnocentrism, suggesting how PTSD may lead to a self-protective
      style of defensive coping.

PMID- 16649866
TI  - Unresolved attachment, PTSD, and dissociation in women with childhood abuse
      histories.
AB  - The primary objective of this study was to examine unresolved trauma as assessed
      by the Adult Attachment Interview and current psychiatric symptoms, focusing on
      posttraumatic stress disorder (PTSD) and dissociation, in a group of adult female
      childhood abuse survivors. The authors examined psychiatric symptoms and
      attachment representations in a group with (n = 30) and without (n = 30) abuse
      related PTSD. The findings revealed that unresolved trauma carried a 7.5-fold
      increase in the likelihood of being diagnosed with PTSD and was most strongly
      associated with PTSD avoidant symptoms rather than dissociative symptoms. The
      utility of a PTSD framework for understanding unresolved trauma and the role of
      intentional avoidance of trauma cues in the maintenance of traumatized states of
      mind are discussed.

PMID- 16649867
TI  - Women's history of sexual abuse, their sexuality, and sexual self-schemas.
AB  - In this study, the authors assessed 48 female survivors of child sexual abuse
      (CSA) and 71 female control participants using measures of adult sexual function,
      psychological function (i.e., depression and anxiety), and sexual self-schemas.
      The primary purpose of this study was to examine whether differences existed
      between women with and without a history of CSA in the way that they viewed
      themselves as a sexual person and, if so, whether such differences mediated the
      link between early unwanted sexual experiences and later adult sexuality. CSA
      survivors were found to view themselves as less romantic and passionate than
      women who were not abused. In particular, CSA survivors showed an inverse
      relationship between romantic/passionate sexual self-schemas and negative sexual
      affect during sexual arousal. The relationship between CSA and negative sexual
      affect was independent from symptoms of depression and anxiety, suggesting that
      the impact of CSA on sexual self-schemas may be independent from the impact that
      the abuse may have in other areas of the survivor's life.

PMID- 16649868
TI  - Clinical characteristics of adults reporting repressed, recovered, or continuous
      memories of childhood sexual abuse.
AB  - The authors assessed women and men who either reported continuous memories of
      their childhood sexual abuse (CSA, n = 92), reported recovering memories of CSA
      (n = 38), reported believing they harbored repressed memories of CSA (n = 42), or
      reported never having been sexually abused (n = 36). Men and women were
      indistinguishable on all clinical and psychometric measures. The 3 groups that
      reported abuse scored similarly on measures of anxiety, depression, dissociation,
      and absorption. These groups also scored higher than the control group.
      Inconsistent with betrayal trauma theory, recovered memory participants were not
      more likely to report abuse by a parent or stepparent than were continuous memory
      participants. Rates of depression and posttraumatic stress disorder did not
      differ between the continuous and recovered memory groups.

PMID- 16649869
TI  - Does expressive writing reduce health care utilization? A meta-analysis of
      randomized trials.
AB  - This meta-analysis examined whether writing about stressful experiences affects
      health care utilization (HCU) compared with writing on neutral topics or no
      writing control groups. Randomized controlled trials of 30 independent samples
      representing 2,294 participants were located that contained sufficient
      information to calculate effect sizes. After omitting one study as an outlier,
      the effects were combined within 3 homogeneous groups: healthy samples (13
      studies), samples with preexisting medical conditions (6 studies), and samples
      prescreened for psychological criteria (10 studies). Combined effect sizes,
      Hedges's g (95% confidence interval), with random effects estimation were 0.16
      (0.02, 0.31), 0.21 (-0.02, 0.43), and 0.06 (-0.12, 0.24), respectively. Writing
      about stressful experiences reduces HCU in healthy samples but not in samples
      defined by medical diagnoses or exposure to stress or other psychological
      factors. The significance of these effects for individuals' health is unknown.

PMID- 16649870
TI  - Mediation and moderation of psychological pain treatments: response expectancies
      and hypnotic suggestibility.
AB  - The mediator role of response expectancies and the moderator role of hypnotic
      suggestibility were evaluated in the analogue treatment of pain. Approximately
      1,000 participants were assessed for hypnotic suggestibility. Later, as part of a
      seemingly unrelated experiment, 188 of these individuals were randomly assigned
      to distraction, cognitive-behavioral package, hypnotic cognitive-behavioral
      package, hypnotic analgesia suggestion, placebo control, or no-treatment control
      conditions. Response expectancies partially mediated the effects of treatment on
      pain. Hypnotic suggestibility moderated treatment and was associated with the
      relief produced only by the hypnotic interventions. The results suggest that
      response expectancies are an important mechanism of hypnotic and cognitive
      behavioral pain treatments and that hypnotic suggestibility is a trait variable
      that predicts hypnotic responding across situations, including hypnosis-based
      pain interventions.

PMID- 16649871
TI  - Dissonance and healthy weight eating disorder prevention programs: a randomized
      efficacy trial.
AB  - In this trial, adolescent girls with body dissatisfaction (N = 481, M age = 17
      years) were randomized to an eating disorder prevention program involving
      dissonance-inducing activities that reduce thin-ideal internalization, a
      prevention program promoting healthy weight management, an expressive writing
      control condition, or an assessment-only control condition. Dissonance
      participants showed significantly greater reductions in eating disorder risk
      factors and bulimic symptoms than healthy weight, expressive writing, and
      assessment-only participants, and healthy weight participants showed
      significantly greater reductions in risk factors and symptoms than expressive
      writing and assessment-only participants from pretest to posttest. Although these
      effects faded over 6-month and 12-month follow-ups, dissonance and healthy weight
      participants showed significantly lower binge eating and obesity onset and
      reduced service utilization through 12-month follow-up, suggesting that both
      interventions have public health potential.

PMID- 16649872
TI  - Analyzing milestones in smoking cessation: illustration in a nicotine patch trial
      in adult smokers.
AB  - Tests of addiction treatments seldom reveal where treatment exercises its effect
      (i.e., promoting initial abstinence, preventing lapses, and/or impeding
      progression from lapse to relapse). The authors illustrate analyses
      distinguishing effects on these milestones in a randomized trial of high-dose
      nicotine patch (35 mg; n = 188) versus placebo (n = 136) in adult smokers, who
      used electronic diaries to monitor smoking in real time during 5 weeks of
      treatment. High-dose patch promoted initial abstinence (hazard ratio [HR] = 1.3)
      and decreased the risk of lapsing among those who achieved abstinence (HR = 1.6).
      The biggest effect of treatment was to prevent progression to relapse among those
      who had lapsed (HR = 7.1). Analysis of effects by milestones may enhance
      understanding of cessation treatments and their mechanisms of action.

PMID- 16649873
TI  - Extended treatment with bupropion SR for cigarette smoking cessation.
AB  - The authors present results of a randomized clinical trial of the efficacy of
      extended treatment with bupropion SR in producing longer term cigarette smoking
      cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that
      combined relapse prevention training, bupropion SR, and nicotine patch followed
      by extended treatment (14 weeks) with bupropion SR or matching placebo.
      Abstinence percentages were relatively high (week 11: 52%; week 25: bupropion,
      42%; placebo, 38%; week 52: bupropion, 33%; placebo, 34%), but bupropion SR did
      not surpass placebo. Gender and baseline craving level were identified as
      significant, independent moderators of treatment response. Men were more likely
      to abstain than women (week 11: 59% vs. 43%, p = .001; week 25: 48% vs. 31%, p =
      .001; week 52: 39% vs. 27%, p = .01). Because most smokers suffer relapse with
      any current cessation treatment, the comparatively high abstinence percentages
      achieved in this trial are of interest.

PMID- 16649874
TI  - Efficacy of a tailored tobacco control program on long-term use in a population
      of U.S. military troops.
AB  - The authors evaluated the effect of a brief tailored smoking control intervention
      delivered during basic military training on tobacco use in a population of
      military personnel (N = 33,215). Participants were randomized to either a tobacco
      use intervention (smoking cessation, smokeless tobacco use cessation, or
      prevention depending on tobacco use history) or a health education control
      condition. Results indicated that smokers who received intervention were 1.16
      (95% confidence interval [CI] = 1.04, 1.30) times (7-day point prevalence) and
      1.23 (95% CI = 1.07, 1.41) times (continuous abstinence) more likely to be
      abstinent than controls from smoking cigarettes at the 1-year follow-up (p <
      .01); the cessation rate difference was 1.60% (31.09% vs. 29.49%) and 1.73%
      (15.47% vs. 13.74%) for point prevalence and continuous abstinence, respectively.
      Additionally, smokeless tobacco users were 1.33 (95% CI = 1.08, 1.63) times more
      likely than controls (p < .01) continuously abstinent at follow-up, an overall
      cessation rate difference of 5.44% (33.72% vs. 28.28%). The smoking prevention
      program had no impact on smoking initiation. These results suggest potential for
      large-scale tobacco control efforts.

PMID- 16649875
TI  - Clinical trial of abstinence-based vouchers and cognitive-behavioral therapy for
      cannabis dependence.
AB  - Ninety cannabis-dependent adults seeking treatment were randomly assigned to
      receive cognitive-behavioral therapy, abstinence-based voucher incentives, or
      their combination. Treatment duration was 14 weeks, and outcomes were assessed
      for 12 months posttreatment. Findings suggest that (a) abstinence-based vouchers
      were effective for engendering extended periods of continuous marijuana
      abstinence during treatment, (b) cognitive-behavioral therapy did not add to this
      during-treatment effect, and (c) cognitive-behavioral therapy enhanced the
      posttreatment maintenance of the initial positive effect of vouchers on
      abstinence. This study extends the literature on cannabis dependence, indicating
      that a program of abstinence-based vouchers is a potent treatment option.
      Discussion focuses on the strengths of each intervention, the clinical
      significance of the findings, and the need to continue efforts toward development
      of effective interventions.

PMID- 16649876
TI  - Significance of a behavioral economic index of reward value in predicting
      drinking problem resolution.
AB  - This study investigated whether a behavioral economic index of the value of
      rewards available over different time horizons improved prediction of drinking
      outcomes beyond established biopsychosocial predictors. Preferences for immediate
      drinking versus more delayed rewards made possible by saving money were
      determined from expenditures prior to resolution attempts by problem drinkers
      with different help-seeking experiences (N = 144). As hypothesized, stable
      resolutions over a 2-year follow-up were associated with proportionally more
      preresolution discretionary expenditures on savings and less on alcohol compared
      with unstable resolutions. The relationship held regardless of help-seeking
      history, and preresolution drinking practices, problems, and income were similar
      across outcomes. The findings extend experimental work on behavioral economics
      and indicate that measuring monetary allocation improves prediction of outcomes.

PMID- 16649877
TI  - Universal session-level change processes in an early session of psychotherapy:
      path models.
AB  - The authors used structural equation modeling to investigate universal change
      processes identified in the generic model of psychotherapy (GMP). Three path
      models of increasing complexity were examined in Study 1 in dynamic therapy. The
      best fitting model from Study 1 was replicated in Study 2 for participants
      receiving either cognitive or interpersonal therapy. Findings provided support
      for the universality of the GMP constructs in different types of therapy.
      Positive influences for therapeutic bond, openness, and realizations were
      observed, as was a surprising negative impact for one aspect of bond. Discussion
      highlights a complex conception of the therapy relationship that underscores the
      importance of investigating the multiple functions that the therapy relationship
      might serve in different psychotherapies.

PMID- 16649878
TI  - Early alliance, alliance ruptures, and symptom change in a nonrandomized trial of
      cognitive therapy for avoidant and obsessive-compulsive personality disorders.
AB  - Participants were 30 adult outpatients diagnosed with avoidant personality
      disorder or obsessive-compulsive personality disorder who enrolled in an open
      trial of cognitive therapy for personality disorders. Treatment consisted of up
      to 52 weekly sessions. Symptom evaluations were conducted at intake, at Sessions
      17 and 34, and at the last session. Alliance variables were patients' first
      alliance rating and "rupture-repair" episodes, which are disruptions in the
      therapeutic relationship that can provide corrective experiences and facilitate
      change. Stronger early alliances and rupture-repair episodes predicted more
      improvement in symptoms of personality disorder and depression. This work points
      to potentially important areas to target in treatment development for these
      personality disorders.

PMID- 16649879
TI  - Pretreatment social relations, therapeutic alliance, and improvements in
      parenting practices in parent management training.
AB  - The authors examined the parent-therapist alliance in parent management training
      for children (N = 218; 53 girls and 165 boys, ages 2-14) referred clinically for
      oppositional, aggressive, and antisocial behavior. The interrelations of
      pretreatment parent social relationships, the parent-therapist alliance over the
      course of treatment, and improvements in parenting practices at the end of
      treatment were evaluated by different raters. As expected, the better the quality
      of the parent-therapist alliance, the greater the improvements in parenting
      practices by the end of treatment. Social relations of the parents prior to
      treatment were associated with the parent-therapist alliance during treatment and
      parental improvements at the end of treatment. The relation between the
      therapeutic alliance and improvement in parenting practices was partially
      explained by pretreatment parent social relations.

PMID- 16649880
TI  - The Strong African American Families Program: a cluster-randomized prevention
      trial of long-term effects and a mediational model.
AB  - The Strong African American Families Program, a universal preventive intervention
      to deter alcohol use among rural African American adolescents, was evaluated in a
      cluster-randomized prevention trial. This 7-week family skills training program
      is based on a contextual model in which intervention effects on youth protective
      factors lead to changes in alcohol use. African American 11-year-olds and their
      primary caregivers from 9 rural communities (N = 332 families) were randomly
      selected for study participation. Communities were randomized to prevention and
      control conditions. Intent-to-treat analyses indicated that fewer prevention than
      control adolescents initiated alcohol use; those who did evinced slower increases
      in use over time. Intervention-induced changes in youth protective factors
      mediated the effect of group assignment on long-term changes in use.

PMID- 16649881
TI  - Self-system therapy as an intervention for self-regulatory dysfunction in
      depression: a randomized comparison with cognitive therapy.
AB  - Self-system therapy (SST) is a new therapy based on regulatory focus theory (E.
      T. Higgins, 1997) for depressed individuals unable to pursue promotion goals
      effectively. The authors conducted a randomized trial comparing SST with
      cognitive therapy (CT) in a sample of 45 patients with a range of depressive
      symptoms to test 2 hypotheses: that SST would be more efficacious for depressed
      individuals characterized by inadequate socialization toward pursuing promotion
      goals and that SST would lead to greater reduction in dysphoric responses to
      priming of promotion goals. There was no overall difference in efficacy between
      treatments, but patients whose socialization history lacked an emphasis on
      promotion goals showed significantly greater improvement with SST. In addition,
      SST patients showed a greater reduction in dysphoric responses to promotion goal
      priming than did CT patients. The results illustrate the value of a theory-based
      translational approach to treatment design and selection.

PMID- 16649882
TI  - Effectiveness of cognitive-behavioral treatment for panic disorder versus
      treatment as usual in a managed care setting: 2-year follow-up.
AB  - Eighty clients meeting criteria for panic disorder and receiving either panic
      control therapy (PCT; M. G. Craske, E. Meadows, & D. H. Barlow, 1994) or
      treatment as usual (TAU) in a managed care setting were assessed 1 and 2 years
      following acute treatment. PCT was provided by therapists with little or no
      previous exposure to cognitive-behavioral therapies. Analyses of the full intent
      to-treat sample revealed no significant differences between the treatments across
      the follow-up period. However, when treatment completer status was added as a
      moderator, those receiving PCT showed lower levels of panic severity and phobic
      avoidance and a greater likelihood of achieving and maintaining clinically
      significant change. Benzodiazepine use during follow-up was associated with
      greater panic severity for those clients who received PCT, but no such
      relationship was found for TAU clients. Results are discussed in relation to the
      dissemination and effectiveness of PCT as well as evidence-based psychotherapies
      more generally.

PMID- 16649883
TI  - Do black and white youths differ in levels of psychopathic traits? A meta
      analysis of the psychopathy checklist measures.
AB  - Putative ethnic group differences in various forms of psychopathology may have
      important theoretical, clinical, and policy implications. Recently, it has been
      argued that individuals of African descent are more likely to be psychopathic
      than those of European descent (R. Lynn, 2002). Preliminary evidence from the
      Psychopathy Checklist: Youth Version (A. Forth, D. Kosson, & R. Hare, 2003)
      offers some support for this contention, with Black youths rated as moderately
      higher (Cohen's d = .61) than White youths in a large institutional sample (n =
      945). To examine this issue more exhaustively, the authors meta-analyzed
      adolescent psychopathy data from several studies (combined N = 2,199) and
      obtained a much smaller mean difference (dw = .20, p = .03), although
      considerable heterogeneity was evident among the effect sizes.

PMID- 16649884
TI  - A randomized clinical trial of a brief, mailed intervention for symptoms of
      depression.
AB  - This research evaluated the efficacy of a brief, mailed personalized feedback
      intervention designed to alleviate depressed mood and antecedents (ineffective
      coping and hopelessness). College students (N = 177) were randomly assigned to
      intervention or control group following a baseline assessment. A week after
      completing the baseline assessment, participants in the intervention condition
      were mailed feedback and information detailing their mood, coping strategies, as
      well as suggestions for enhancing mood. Results indicated that feedback was
      effective in reducing depressive symptoms, hopelessness, and among men,
      increasing willingness to use coping strategies at the 1-month follow-up.
      Hopelessness mediated reductions in depressive symptoms. Results support the use
      of personalized feedback as a low-cost, initial intervention for college students
      suffering from symptoms of depression.

PMID- 16649885
TI  - III STEP: a basic scientist's perspective.

PMID- 16649886
TI  - Time dependency of walking classification in stroke.
AB  - BACKGROUND AND PURPOSE: To facilitate optimal stroke rehabilitation, valid
      interpretation of observed functional recovery is required. The purpose of this
      study was to examine the longitudinal relationship between comfortable walking
      speed and Functional Ambulation Categories (FAC) scores for physically
      independent gait. SUBJECTS: This study was a prospective cohort study with 73
      subjects who were severely affected by acute stroke. METHODS: Functional
      Ambulation Categories classification and walking speed were measured between
      weeks 4 and 26 after stroke. The responsiveness of walking speed measurements for
      detecting clinically important speed changes was determined, and the longitudinal
      association between walking speed and FAC scores and its time dependency were
      established. This relationship subsequently was scrutinized for possible speed
      changes occurring within specific FAC scores. Responsiveness ratios, random
      coefficient analysis, paired Student t tests, and the Cohen kappa statistic were
      used for statistical analyses. RESULTS: Responsiveness ratios exceeded the
      smallest detectable differences. Random coefficient analysis demonstrated a
      significant between- and within-subject coefficient and a significant negative
      interaction between timing of measurements and FAC scores. Paired Student t tests
      revealed mostly significant pretest-posttest differences in walking speeds, and
      all kappa values for pretest-posttest FAC scores were significant. DISCUSSION AND
      CONCLUSION: Walking speed measurements are sensitive for detecting clinically
      important changes. Functional Ambulation Categories scores are dependent on the
      timing of comfortable walking speed measurements after stroke. Moreover, there
      are indications that, in this relationship, repeated FAC appraisals are not only
      based on steady walking speeds, but that the walking speeds related to a specific
      FAC appraisal also change and, over time, may shift gradually from higher to
      lower speeds.

PMID- 16649887
TI  - Effects of exercise training on heart rate variability after coronary
      angioplasty.
AB  - BACKGROUND AND PURPOSE: Cardiac autonomic dysfunction is associated with risk of
      restenosis and cardiovascular mortality in patients after percutaneous
      transluminal coronary angioplasty (PTCA). Analysis of heart rate variability
      (HRV) is an important, widely used method for assessing cardiac autonomic
      regulation. The purpose of this study was to investigate the effect of exercise
      training on HRV in subjects after PTCA. SUBJECTS AND METHODS: A total of 84
      subjects who had undergone PTCA were recruited for this study. The subjects (age
      [mean+/-SD]=57.0+/-9.3 years) were randomly assigned to either an exercise group
      to undergo an 8-week outpatient exercise program or a control group to undergo
      usual care. Heart rate variability was measured for 5 minutes in the supine
      resting position at baseline and at the end of 8 weeks. RESULTS: The
      parasympathetically modulated HRV of the subjects in the exercise group increased
      significantly compared with the HRV of subjects in the control group. The effects
      of training on HRV were independent of angioplasty type (balloon or stent) and
      were unrelated to whether the subjects had received previous PTCA. DISCUSSION AND
      CONCLUSION: Exercise training can increase parasympathetic modulation of cardiac
      function in people after they have undergone successful PTCA. Our results suggest
      that analysis of HRV can be extended to assess the effect of exercise training on
      cardiac autonomic dysfunction in people after coronary angioplasty.

PMID- 16649888
TI  - Passive leg movements and passive cycling do not alter arterial leg blood flow in
      subjects with spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Subjects with a spinal cord injury (SCI) are at increased
      risk for cardiovascular disease-related secondary complications, such as pressure
      ulcers and attenuated wound healing. It has been suggested that passive exercise
      enhances blood flow via mechanical pump effects or reflex activation. The purpose
      of this study was to assess the effects of passive leg movements and passive
      cycling on the arterial circulation in subjects with SCI. SUBJECTS: Eight men
      with motor complete SCI and 8 male control subjects participated. METHODS: Echo
      Doppler measurements were obtained to measure leg blood flow at rest, during and
      after 10 minutes of standardized passive leg movements, and during and after 20
      minutes of passive leg cycling. Blood pressure was measured continuously, and
      total vascular resistance and leg vascular resistance were calculated. RESULTS:
      In both groups, no changes in leg blood flow, vascular resistance, or blood
      pressure were observed during or after the 2 interventions. DISCUSSION AND
      CONCLUSION: The results of the study demonstrate that passive leg movements and
      passive cycling do not alter the arterial peripheral circulation in subjects with
      SCI or control subjects. Although the results do not support the use of passive
      movements or exercise for the prevention of cardiovascular disease-related
      secondary complications, physical therapists should not be dissuaded from using
      these techniques to address musculoskeletal concerns.

PMID- 16649889
TI  - Timed "Up & Go" test: reliability in older people dependent in activities of
      daily living--focus on cognitive state.
AB  - BACKGROUND AND PURPOSE: It is unknown how cognitive impairment affects the
      reliability of Timed "Up & Go" Test (TUG) scores. The aim of the present study
      was to investigate the expected variability of TUG scores in older subjects
      dependent in activities of daily living (ADL) and with different levels of
      cognitive state. The hypothesis was that cognitive impairment would increase the
      variability of TUG scores. SUBJECTS: Seventy-eight subjects with multiple
      impairments, dependent in ADL, and living in residential care facilities were
      included in this study. The subjects were 84.8+/-5.7 (mean+/-SD) years of age,
      and their Mini-Mental State Examination score was 18.7+/-5.6. METHODS: The TUG
      assessments were performed on 3 different days. Intrarater and interrater
      analyses were carried out. RESULTS: Cognitive impairment was not related to the
      size of the variability of TUG scores. There was a significant relationship
      between the variability and the time taken to perform the TUG. The intraclass
      correlations were greater than .90 and were similar within and between raters. In
      repeated measurements at the individual level, an observed value of 10 seconds
      was expected to vary from 7 to 15 seconds and an observed value of 40 seconds was
      expected to vary from 26 to 61 seconds for 95% of the observations. DISCUSSION
      AND CONCLUSION: The measurement error of a TUG assessment is substantial for a
      frail older person dependent in ADL, regardless of the level of cognitive
      function, when verbal cuing is permitted during testing. The variability
      increases with the time to perform the TUG. Despite high intraclass correlation
      coefficients, the ranges of expected variability can be wide and are similar
      within and between raters. Physical therapists should be aware of this
      variability before they interpret the TUG score for a particular individual.

PMID- 16649890
TI  - Electromyographic analysis of traditional and nontraditional abdominal exercises:
      implications for rehabilitation and training.
AB  - BACKGROUND AND PURPOSE: Performing nontraditional abdominal exercises with
      devices such as abdominal straps, the Power Wheel, and the Ab Revolutionizer has
      been suggested as a way to activate abdominal and extraneous (nonabdominal)
      musculature as effectively as more traditional abdominal exercises, such as the
      crunch and bent-knee sit-up. The purpose of this study was to test the
      effectiveness of traditional and nontraditional abdominal exercises in activating
      abdominal and extraneous musculature. SUBJECTS: Twenty-one men and women who were
      healthy and between 23 and 43 years of age were recruited for this study.
      METHODS: Surface electromyography (EMG) was used to assess muscle activity from
      the upper and lower rectus abdominis, external and internal oblique, rectus
      femoris, latissimus dorsi, and lumbar paraspinal muscles while each exercise was
      performed. The EMG data were normalized to maximum voluntary muscle contractions.
      Differences in muscle activity were assessed by a 1-way, repeated-measures
      analysis of variance. RESULTS: Upper and lower rectus abdominis, internal
      oblique, and latissimus dorsi muscle EMG activity were highest for the Power
      Wheel (pike, knee-up, and roll-out), hanging knee-up with straps, and reverse
      crunch inclined 30 degrees. External oblique muscle EMG activity was highest for
      the Power Wheel (pike, knee-up, and roll-out) and hanging knee-up with straps.
      Rectus femoris muscle EMG activity was highest for the Power Wheel (pike and knee
      up), reverse crunch inclined 30 degrees, and bent-knee sit-up. Lumbar paraspinal
      muscle EMG activity was low and similar among exercises. DISCUSSION AND
      CONCLUSION: The Power Wheel (pike, knee-up, and roll-out), hanging knee-up with
      straps, and reverse crunch inclined 30 degrees not only were the most effective
      exercises in activating abdominal musculature but also were the most effective in
      activating extraneous musculature. The relatively high rectus femoris muscle
      activity obtained with the Power Wheel (pike and knee-up), reverse crunch
      inclined 30 degrees, and bent-knee sit-up may be problematic for some people with
      low back problems.

PMID- 16649891
TI  - Effectiveness of radial shock-wave therapy for calcific tendinitis of the
      shoulder: single-blind, randomized clinical study.
AB  - BACKGROUND AND PURPOSE: Radial shock-wave therapy (RSWT) is a pneumatically
      generated, low- to medium-energy type of shock-wave therapy. This single-blind,
      randomized, "less active similar therapy"-controlled study was performed to
      evaluate the effectiveness of RSWT for the management of calcific tendinitis of
      the shoulder. SUBJECTS: Ninety patients with radiographically verified calcific
      tendinitis of the shoulder were tested. METHODS: Subjects were randomly assigned
      to either a treatment group (n=45) or a control group (n=45). Pain and functional
      level were evaluated before and after treatment and at a 6-month follow-up.
      Radiographic modifications in calcifications were evaluated before and after
      treatment. RESULTS: The treatment group displayed improvement in all of the
      parameters analyzed after treatment and at the 6-month follow-up. Calcifications
      disappeared completely in 86.6% of the subjects in the treatment group and
      partially in 13.4% of subjects; only 8.8% of the subjects in the control group
      displayed partially reduced calcifications, and none displayed a total
      disappearance. DISCUSSION AND CONCLUSION: The results suggest that the use of
      RSWT for the management of calcific tendinitis of the shoulder is safe and
      effective, leading to a significant reduction in pain and improvement of shoulder
      function after 4 weeks, without adverse effects.

PMID- 16649892
TI  - Neuromuscular activation in conventional therapeutic exercises and heavy
      resistance exercises: implications for rehabilitation.
AB  - BACKGROUND AND PURPOSE: Central activation failure and muscular atrophy are
      common after knee joint injury. Thus, exercises that aim to stimulate muscular
      hypertrophy and increase neural drive to the muscle fibers should be used during
      rehabilitation. This study examined the level of knee joint neuromuscular
      activation during 4 conventional therapeutic exercises (quadriceps femoris muscle
      setting, manual lateralization of the patella, rhythmic stabilization, and the
      pelvic bridging exercise) and 4 heavy resistance exercises (free-weight squat
      with a barbell, horizontal seated leg press, isolated knee extension with a cam
      mechanism, and isolated hamstring muscle curl) in young, untrained men who were
      healthy. SUBJECTS: Thirteen male subjects (mean age=25.3 years, SD=3.0) with no
      previous history of knee injury participated in the study. METHODS: Neuromuscular
      activation during the exercises was defined as the root-mean-square (RMS)
      electromyographic (EMG) signal normalized to the peak RMS EMG signal of a maximal
      isometric muscle contraction. RESULTS: Low levels of neuromuscular activation
      were found during all conventional exercises (<35%). A limitation may be that
      only a few of many different conventional exercises were investigated. The
      highest level of neuromuscular activation (67%-79%) was observed during the open
      kinetic chain resistance exercises (isolated knee extension and hamstring muscle
      curl). None of the conventional exercises or heavy resistance exercises were
      found to preferentially activate the vastus medialis muscle over the vastus
      lateralis muscle. DISCUSSION AND CONCLUSION: The results indicate that heavy
      resistance exercises should be included in rehabilitation programs to induce
      sufficient levels of neuromuscular activation to stimulate muscle growth and
      strength.

PMID- 16649893
TI  - Transcutaneous electrical nerve stimulation for the management of neuropathic
      pain: the effects of frequency and electrode position on prevention of allodynia
      in a rat model of complex regional pain syndrome type II.
AB  - BACKGROUND AND PURPOSE: Complex regional pain syndrome type II (CPSII) is a
      painful condition that develops following a nerve injury. Although transcutaneous
      electrical nerve stimulation (TENS) relieves the pain of CPSII, the stimulation
      parameters that would best prevent the development of the condition are not
      known. The purpose of this study was to compare the ability of several different
      stimulation strategies to reduce the development of allodynia. SUBJECTS: Sprague
      Dawley rats were used in the study. METHODS: A chronic constriction injury (CCI)
      to the right sciatic nerve was used to induce allodynia. Two groups of CCI rats
      received high-frequency TENS to the lumbar paravertebral region with electrodes
      positioned on the skin overlying either the right or left paraspinal musculature.
      Two additional groups of CCI rats received low-frequency TENS to acupuncture
      points in the right or left hind limbs. A fifth group of CCI rats received no
      TENS intervention. Thermal and mechanical pain thresholds were assessed in the
      right hind paw before and 12 days after the CCI surgery. The TENS was delivered 1
      hour per day beginning on the day of surgery. RESULTS: Daily high-frequency TENS
      reduced the development of mechanical allodynia in CCI rats, and low-frequency
      TENS reduced the development of thermal allodynia, but only when TENS was
      delivered on the left side. DISCUSSION AND CONCLUSION: The results indicate that
      TENS delivered contralateral to a nerve injury best reduces allodynia
      development. Comprehensive reduction of allodynia development would require a
      combination of high- and low-frequency TENS intervention.

PMID- 16649894
TI  - A systematic review of the effectiveness of physical therapy interventions for
      temporomandibular disorders.
AB  - BACKGROUND AND PURPOSE: The purpose of this qualitative systematic review was to
      assess the evidence concerning the effectiveness of physical therapy
      interventions in the management of temporomandibular disorders. METHODS: A
      literature search of published and unpublished articles resulted in the retrieval
      of 36 potential articles. RESULTS: Twelve studies met all selection criteria for
      inclusion in the review: 4 studies addressed the use of therapeutic exercise
      interventions, 2 studies examined the use of acupuncture, and 6 studies examined
      electrophysical modalities. Two studies provided evidence in support of postural
      exercises to reduce pain and to improve function and oral opening. One study
      provided evidence for the use of manual therapy in combination with active
      exercises to reduce pain and to improve oral opening. One study provided evidence
      in support of acupuncture to reduce pain when compared with no treatment;
      however, in another study no significant differences in pain outcomes were found
      between acupuncture and sham acupuncture. Significant improvements in oral
      opening were found with muscular awareness relaxation therapy, biofeedback
      training, and low-level laser therapy treatment. DISCUSSION AND CONCLUSION: Most
      of the studies included in this review were of very poor methodological quality;
      therefore, the findings should be interpreted with caution.

PMID- 16649895
TI  - Toward a common language for function, disability, and health.
AB  - Within physical therapy, the disablement model has proven useful as a language to
      delineate the consequences of disease and injury. This perspective provides an
      update on the changing language of disablement, reviews selected contemporary
      disablement models, and discusses some challenges that need to be addressed to
      achieve a universal disablement language that can be used to discuss physical
      therapy research and clinical interventions. The World Health Organization's
      International Classification of Functioning, Disability and Health (ICF)
      framework has the potential of becoming a standard for disablement language that
      looks beyond mortality and disease to focus on how people live with their
      conditions. If widely adopted, the ICF framework could provide the rehabilitation
      field with a common, international language with the potential to facilitate
      communication and scholarly discourse across disciplines and national boundaries,
      to stimulate interdisciplinary research, to improve clinical care, and ultimately
      to better inform health policy and management.

PMID- 16649896
TI  - Interpreting change scores of tests and measures used in physical therapy.
AB  - Over the past decade, the methods and science used to describe changes in
      outcomes of physical therapy services have become more refined. Recently,
      emphasis has been placed not only on changes beyond expected measurement error,
      but also on the identification of changes that make a real difference in the
      lives of patients and families. This article will highlight a case example of how
      to determine and interpret "clinically significant change" from both of these
      perspectives. The authors also examine how to use item maps within an item
      response theory model to enhance the interpretation of change at a content level.
      Recommendations are provided for physical therapists who are interpreting changes
      in the context of clinical practice, case reports, and intervention research.
      These recommendations include a greater application of indexes that help
      interpret the meaning of clinically significant change to multiple clinical,
      research, consumer, and payer communities.

PMID- 16649897
TI  - Is there evidence to support the use of constraint-induced therapy to improve the
      quality or quantity of upper extremity function of a 2 1/2-year-old girl with
      congenital hemiparesis? If so, what are the optimal parameters of this
      intervention?

PMID- 16649898
TI  - Minority recruitment and retention.

PMID- 16649899
TI  - Clinical prediction rules.

PMID- 16649900
TI  - Clinical prediction rules.

PMID- 16649901
TI  - In vitro model of cell migration.

PMID- 16649902
TI  - An answer to a call for dialogue on advancing rehabilitation research.

PMID- 16649904
TI  - Questions dosage used in equine study.

PMID- 16649905
TI  - Analytical, physiologic, and clinical validation of a radioimmunoassay for
      measurement of procollagen type III amino terminal propeptide in serum and
      bronchoalveolar lavage fluid obtained from dogs.
AB  - OBJECTIVE: To validate a radioimmunoassay for measurement of procollagen type III
      amino terminal propeptide (PIIINP) concentrations in canine serum and
      bronchoalveolar lavage fluid (BALF) and investigate the effects of physiologic
      and pathologic conditions on PIIINP concentrations. SAMPLE POPULATION: Sera from
      healthy adult (n = 70) and growing dogs (20) and dogs with chronic renal failure
      (CRF; 10), cardiomyopathy (CMP; 12), or degenerative valve disease (DVD; 26); and
      sera and BALF from dogs with chronic bronchopneumopathy (CBP; 15) and healthy
      control dogs (10 growing and 9 adult dogs). PROCEDURE: A radioimmunoassay was
      validated, and a reference range for serum PIIINP (S-PIIINP) concentration was
      established. Effects of growth, age, sex, weight, CRF, and heart failure on S
      PIIINP concentration were analyzed. In CBP-affected dogs, S-PIIINP and BALF
      PIIINP concentrations were evaluated. RESULTS: The radioimmunoassay had good
      sensitivity, linearity, precision, and reproducibility and reasonable accuracy
      for measurement of S-PIIINP and BALF-PIIINP concentrations. The S-PIIINP
      concentration reference range in adult dogs was 8.86 to 11.48 mug/L. Serum PIIINP
      concentration correlated with weight and age. Growing dogs had significantly
      higher S-PIIINP concentrations than adults, but concentrations in CRF-, CMP-, DVD
      , or CBP-affected dogs were not significantly different from control values. Mean
      BALF-PIIINP concentration was significantly higher in CBP-affected dogs than in
      healthy adults. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, renal or cardiac
      disease or CBP did not significantly affect S-PIIINP concentration; dogs with CBP
      had high BALF-PIIINP concentrations. Data suggest that the use of PIIINP as a
      marker of pathologic fibrosis might be limited in growing dogs.

PMID- 16649906
TI  - Correlation of magnetic resonance images with anatomic features of the equine
      tarsus.
AB  - OBJECTIVE: To correlate anatomic features of the equine tarsus identified in
      plastinated sections with images obtained via magnetic resonance imaging (MRI).
      ANIMALS: 4 horses. PROCEDURE: MRI (1.5-Tesla magnet) of the tarsus was performed
      on the pelvic limbs of 4 clinically normal horses following euthanasia. After
      imaging, tarsocrural joint spaces and vasculature were injected with colored
      latex. Sagittal and transverse sections of the tarsi were plastinated to
      facilitate interpretation of MR images. RESULTS: Relevant anatomic structures
      were identified and labeled on the plastinated tissue slices and corresponding MR
      images. Results indicated high correlations between MRI findings and those of
      plastinated sections. CONCLUSIONS AND CLINICAL RELEVANCE: The data obtained
      provided certain reference standards for normal anatomic structure sizes and
      positions in the equine tarsus. This information may aid future physiologic or
      clinical studies of this joint.

PMID- 16649907
TI  - Evaluation of administration of isoflurane at approximately the minimum alveolar
      concentration on depression of a nociceptive withdrawal reflex evoked by
      transcutaneous electrical stimulation in ponies.
AB  - OBJECTIVE: To investigate effects of isoflurane at approximately the minimum
      alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the
      forelimb of ponies as a method for quantifying anesthetic potency. ANIMALS: 7
      healthy adult Shetland ponies. PROCEDURE: Individual MAC (iMAC) for isoflurane
      was determined for each pony. Then, effects of isoflurane administered at 0.85,
      0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR
      threshold was defined electromyographically for the common digital extensor and
      deltoid muscles by stimulating the digital nerve; additional electrical
      stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked
      activity was recorded and analyzed. After the end of anesthesia, the NWR
      threshold was assessed in standing ponies. RESULTS: Mean +/- SD MAC of isoflurane
      was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in
      a concentration-dependent manner during anesthesia, whereas they decreased in
      awake ponies. Significantly higher thresholds were found for the deltoid muscle,
      compared with thresholds for the common digital extensor muscle, in anesthetized
      ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles
      increased as stimulus intensities increased from 3 to 40 mA. A concentration
      dependent depression of evoked reflexes with reduction in slopes of the stimulus
      response functions was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthetic
      induced changes in sensory-motor processing in ponies anesthetized with
      isoflurane at concentrations of approximately 1.0 MAC can be detected by
      assessment of NWR. This method will permit comparison of effects of inhaled
      anesthetics or anesthetic combinations on spinal processing in equids.

PMID- 16649908
TI  - Effect of meloxicam and butorphanol on minimum alveolar concentration of
      isoflurane in rabbits.
AB  - OBJECTIVE: To determine the effects of meloxicam and butorphanol on minimum
      alveolar concentration of isoflurane (MAC(ISO)) in rabbits. ANIMALS: 10 healthy
      young adult female rabbits. PROCEDURE: Rabbits were anesthetized with isoflurane
      on 3 occasions in a blinded, randomized complete block design to determine the
      MAC(ISO) associated with administration of meloxicam (0, 0.3, or 1.5 mg/kg, PO)
      and butorphanol (0.4 mg/kg, IV). The MAC(ISO) was determined by use of a paw
      clamp technique as the end-tidal concentration of isoflurane halfway between the
      values that allowed or inhibited purposeful movement. Rectal temperature, end
      tidal CO2 concentration, heart rate, oxygen saturation, and arterial blood
      pressure were measured to evaluate cardiopulmonary function. RESULTS: Mean +/- SE
      MAC(ISO) in saline (0.9% NaCl) solution-treated rabbits was 2.49 +/- 0.07% and
      was not significantly different from that associated with administration of
      meloxicam at 0.3 mg/kg (2.56 +/- 0.07%) or 1.5 mg/kg (2.66 +/- 0.07%).
      Butorphanol significantly reduced the MAC(ISO) to 2.30 +/- 0.07% when
      administered with saline solution alone, 2.27 +/- 0.07% when administered with
      0.3 mg of meloxicam/kg, and 2.33 +/- 0.07% when administered with 1.5 mg of
      meloxicam/kg. The percentage reduction in MAC(ISO) was significantly greater for
      rabbits that received butorphanol and meloxicam at either dose, compared with
      butorphanol and saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that meloxicam does not have a direct isoflurane-sparing effect and
      does not interfere with the anesthetic-sparing effect of butorphanol in rabbits.

PMID- 16649909
TI  - Serum concentrations and analgesic effects of liposome-encapsulated and standard
      butorphanol tartrate in parrots.
AB  - OBJECTIVE: To compare serum concentrations of liposome-encapsulated butorphanol
      tartrate (LEBT) and standard butorphanol tartrate (STDBT) following SC and IM
      administration, respectively, and to evaluate analgesic effects of LEBT and STDBT
      after parenteral administration to Hispaniolan parrots. ANIMALS: 11 adult
      Hispaniolan parrots. PROCEDURE: The ability of LEBT to prolong the duration of
      analgesia in an avian species was tested. Blood samples were collected at serial
      time points after SC administration of LEBT (10 mg/kg or 15 mg/kg) or IM
      administration of STDBT (5 mg/kg). Serum concentrations of butorphanol tartrate
      were determined by use of a commercial immunoassay that measured parent drug and
      metabolites. Analgesic efficacy was evaluated in parrots exposed to electrical
      and thermal stimuli. Foot withdrawal thresholds were recorded at baseline and at
      serial time points after LEBT (15 mg/kg), liposome vehicle, STDBT (2 mg/kg), or
      physiologic saline (0.9% NaCl) solution administration. RESULTS: LEBT had a
      prolonged in vivo release for up to 5 days. Negligible serum butorphanol and
      butorphanol metabolite concentrations were obtained at 24 hours after IM
      administration of STDBT. Analgesic efficacy of LEBT as measured by foot
      withdrawal threshold to noxious thermal and electrical stimuli persisted for 3 to
      5 days following SC administration of LEBT. CONCLUSIONS AND CLINICAL RELEVANCE:
      SC administration of LEBT provided analgesia and detectable serum butorphanol
      concentrations in Hispaniolan parrots for up to 5 days. The use of LEBT may allow
      for substantial improvement in long-term pain relief without subjecting birds to
      the stress of handling and multiple daily injections.

PMID- 16649910
TI  - Effect of medetomidine on respiration and minimum alveolar concentration in
      halothane- and isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To evaluate the effect of medetomidine on minimum alveolar
      concentration (MAC), respiratory rate, tidal volume, minute volume (V(M)), and
      maximum inspiratory occlusion pressure (IOCP(max)) in halothane- and isoflurane
      anesthetized dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females).
      PROCEDURE: The MAC of both inhalants was determined before and 5, 30, and 60
      minutes after administration of medetomidine (5 microg/kg, IV). Dogs were
      subsequently anesthetized by administration of halothane or isoflurane and
      administered saline (0.9% NaCl) solution IV or medetomidine (5 microg/kg, IV).
      Respiratory variables and IOCP(max) were measured at specific MAC values 15
      minutes before and 5, 30, and 60 minutes after IV administration of medetomidine
      while dogs breathed 0% and 10% fractional inspired carbon dioxide (FICO2). Slopes
      of the lines for VM/FICO2 and IOCP(max)/FICO2 were then calculated. RESULTS:
      Administration of medetomidine decreased MAC of both inhalants. Slope of
      V(M)/FICO2 increased in dogs anesthetized with halothane after administration of
      medetomidine, compared with corresponding values in dogs anesthetized with
      isoflurane. Administration of medetomidine with a simultaneous decrease in
      inhalant concentration significantly increased the slope for V(M)/FICO2, compared
      with values after administration of saline solution in dogs anesthetized with
      halothane but not isoflurane. Values for IOCP(max) did not differ significantly
      between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Equipotent doses of halothane
      and isoflurane have differing effects on respiration that are most likely
      attributable to differences in drug effects on central respiratory centers.
      Relatively low doses of medetomidine decrease the MAC of halothane and isoflurane
      in dogs.

PMID- 16649911
TI  - Evaluation of delayed-image bone scintigraphy to assess bone formation after
      distraction osteogenesis in dogs.
AB  - OBJECTIVE: To quantitatively assess distraction-induced bone formation in a
      crural lengthening model in dogs by use of delayed-image bone scintigraphy.
      ANIMALS: 12 mature Labrador Retrievers. PROCEDURE: Dogs were randomly allocated
      to 1 of 3 groups. A circular external skeletal fixation system was mounted on the
      right crus of each dog. Osteotomy of the distal portion of the tibia and fibula
      was performed in groups 1 and 2 and was followed by a lengthening procedure of 10
      mm in the first group only. The third group served as sham-operated controls.
      Delayed-image bone scintigraphy with technetium-99m hydroxy methylene
      diphosphonate was performed 2, 4, and 6 weeks after surgery. Delayed-image-to
      region-of-interest, delayed-image-to-crural, and delayed-image-to-femoral
      scintigraphic activity ratios were calculated. New bone formation was quantified
      by use of densitometric image analysis, and values for the scintigraphic ratios
      were compared. RESULTS: In the distraction and osteotomy groups, delayed-image-to
      region-of-interest and delayed-image-to-crural ratios increased significantly.
      Although densitometric image analysis revealed increased bone formation after
      distraction, the region-of-interest ratios and crural ratios were similar in both
      groups. All dogs had increased delayed-image-to-femoral ratios. CONCLUSIONS AND
      CLINICAL RELEVANCE: Delayed-image bone scintigraphy ratios were not effective at
      differentiating between the amounts of distraction-induced bone and osteotomy
      induced bone. Metabolic bone activity in the adjacent femur was increased as a
      consequence of circular external skeletal fixator placement. Delayed-image bone
      scintigraphy was not adequately sensitive to quantitatively monitor bone
      formation but may be useful as an early predictor of bone healing.

PMID- 16649912
TI  - Assessment of bone mineral density of the femoral head in dogs with early
      osteoarthritis.
AB  - OBJECTIVE: To compare the bone mineral density (BMD) of the proximal portion of
      the femur in dogs with and without early osteoarthritis secondary to hip
      dysplasia. ANIMALS: 24 dogs (3 Greyhounds, 6 Labrador-Greyhound crossbreeds, and
      15 Labrador Retrievers). PROCEDURE: Computed tomography (CT) of the pelvis,
      including a bone-density phantom, was performed for each dog. Centrally located
      transverse CT slices and a computer workstation were used to identify 16 regions
      of interest (ROIs) in the proximal portion of the femur. For each ROI, the mean
      Hounsfield unit value was recorded; by use of the bone-density phantom and linear
      regression analysis, those values were converted to equivalent BMD (eBMD). Mean
      eBMD values for the subchondral and nonsubchondral ROIs in dogs with and without
      osteoarthritis (determined at necropsy) were compared. A mixed-model ANOVA and
      post hoc linear contrasts were used to evaluate the effects of osteoarthritis,
      breed, and sex on the BMD value. RESULTS: At necropsy, osteoarthritis was
      detected in 14 hip joints in 9 dogs; all lesions included early cartilage
      fibrillation. After adjusting for breed and sex, eBMD in subchondral ROIs 8 and
      12 (adjacent to the fovea) were 8% and 6% higher, respectively, in osteoarthritis
      affected dogs, compared with unaffected dogs; in the nonsubchondral ROIs, eBMD
      was 10% higher in osteoarthritis-affected dogs. CONCLUSIONS AND CLINICAL
      RELEVANCE: Compared with findings in unaffected dogs, increased eBMD in hip
      joints of dogs with early osteoarthritis supports a strong relationship between
      the subchondral and epiphyseal regions and articular cartilage in the
      pathogenesis and progression of osteoarthritis.

PMID- 16649913
TI  - Effect of changes in ionized calcium concentration in arterial blood and
      metabolic acidosis on the arterial partial pressure of oxygen in dogs.
AB  - OBJECTIVE: To evaluate the effects of metabolic acidosis and changes in ionized
      calcium (Ca2+) concentration on PaO2 in dogs. ANIMALS: 33 anesthetized dogs
      receiving assisted ventilation. PROCEDURE: Normal acid-base status was maintained
      in 8 dogs (group I), and metabolic acidosis was induced in 25 dogs. For 60
      minutes, normocalcemia was maintained in group I and 10 other dogs (group II),
      and 10 dogs were allowed to become hypercalcemic (group III); hypocalcemia was
      then induced in groups I and II. Groups II and IV (5 dogs) were treated
      identically except that, at 90 minutes, the latter underwent parathyroidectomy.
      At intervals, variables including PaO2, Ca2+ concentration, arterial blood pH
      (pHa), and systolic blood pressure were assessed. RESULTS: In group II, PaO2
      increased from baseline value (96 +/- 2 mm Hg) within 10 minutes (pHa, 7.33 +/-
      0.001); at 60 minutes (pHa, 7.21 +/- 0.02), PaO2 was 108 +/- 2 mm Hg. For the
      same pHa decrease, the PaO2 increase was less in group III. In group I,
      hypocalcemia caused PaO2 to progressively increase (from 95 +/- 2 mm Hg to 104 +/
      3 mm Hg), which correlated (r = -0.66) significantly with a decrease in systolic
      blood pressure (from 156 +/- 9 mm Hg to 118 +/- 10 mm Hg). Parathyroidectomy did
      not alter PaO2 values. CONCLUSIONS AND CLINICAL RELEVANCE: Induction of
      hypocalcemia and metabolic acidosis each increased PaO2 in anesthetized dogs,
      whereas acidosis-induced hypercalcemia attenuated that increase. In anesthetized
      dogs, development of metabolic acidosis or hypocalcemia is likely to affect
      ventilatory control.

PMID- 16649914
TI  - Detection of autoantibodies against thyroid peroxidase in serum samples of
      hypothyroid dogs.
AB  - OBJECTIVE: To establish a sensitive test for the detection of autoantibodies
      against thyroid peroxidase (TPO) in canine serum samples. SAMPLE POPULATION: 365
      serum samples from dogs with hypothyroidism as determined on the basis of serum
      concentrations of total and free triiodothyronine (T3), total and free thyroxine
      (T4), and thyroid-stimulating hormone, of which 195 (53%) had positive results
      for at least 1 of 3 thyroid autoantibodies (against thyroglobulin [Tg], T4, or
      T3) and serum samples from 28 healthy dogs (control samples). PROCEDURE: TPO was
      purified from canine thyroid glands by extraction with detergents,
      ultracentrifugation, and precipitation with ammonium sulfate. Screening for anti
      TPO autoantibodies in canine sera was performed by use of an immunoblot assay.
      Thyroid extract containing TPO was separated electrophoretically, blotted, and
      probed with canine sera. Alkaline phosphatase-conjugated rabbit anti-dog IgG was
      used for detection of bound antibodies. RESULTS: TPO bands were observed at 110,
      100, and 40 kd. Anti-TPO autoantibodies against the 40-kd fragment were detected
      in 33 (17%) sera of dogs with positive results for anti-Tg, anti-T4, or anti-T3
      autoantibodies but not in sera of hypothyroid dogs without these autoantibodies
      or in sera of healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The immunoblot
      assay was a sensitive and specific method for the detection of autoantibodies
      because it also provided information about the antigen. Anti-TPO autoantibodies
      were clearly detected in a fraction of hypothyroid dogs. The value of anti-TPO
      autoantibodies for use in early diagnosis of animals with thyroid gland diseases
      should be evaluated in additional studies.

PMID- 16649915
TI  - Effect of intraluminal distension or ischemic strangulation obstruction of the
      equine jejunum on jejunal motilin receptors and binding of erythromycin
      lactobionate.
AB  - OBJECTIVE: To determine whether inflammation of the jejunum of horses decreases
      the number of motilin receptors and amounts of motilin receptor mRNA and alters
      erythromycin lactobionate binding affinity to the motilin receptor in jejunal
      tissues. SAMPLE POPULATION: Jejunal segments in 6 adult horses. PROCEDURE: Each
      horse was anesthetized, and a ventral median celiotomy was performed; 2 segments
      of jejunum underwent a sham operation, 2 segments underwent ischemic
      strangulation obstruction (ISO), and 2 segments underwent intraluminal distension
      (ILD). Treatments were maintained for 120 minutes. From each segment, full
      thickness biopsy samples were collected and smooth-muscle homogenates were
      prepared. Affinity and distribution of motilin binding to these preparations were
      determined by use of iodine 125 (125I)-labeled synthetic porcine motilin. Via
      displacement experiments, competition between 125I-labeled motilin and
      erythromycin lactobionate for binding to motilin receptors in the different
      segments was investigated. A quantitative real-time PCR technique was used to
      assess motilin receptor mRNA content in the muscle preparations. RESULTS:
      Compared with the ISO or ILD segments, the number of motilin receptors was
      significantly higher in the sham-operated segments; ILD segments contained the
      lowest number of motilin receptors. The expression of motilin receptor mRNA was
      significantly decreased in ILD segments but not in ISO segments. Erythromycin
      lactobionate displacement of 125I-labeled motilin from motilin receptors did not
      differ significantly among the jejunal segments. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that downregulation and decreased production of
      motilin receptors in inflamed jejunal tissue contribute to the altered prokinetic
      response to erythromycin in horses with gastrointestinal disease.

PMID- 16649916
TI  - Evaluation of cost-effectiveness of targeted sampling methods for detection of
      Mycobacterium avium subsp paratuberculosis infection in dairy herds.
AB  - OBJECTIVE: To investigate the epidemiologic and financial impacts of targeted
      sampling of subpopulations of cows, compared with random sampling of all cows,
      for classification of dairy herd infection status for paratuberculosis. ANIMALS:
      All cows from 4 infected herds with a low-to-moderate prevalence of
      paratuberculosis and from 1 noninfected herd in California. PROCEDURE: The
      infection status of each cow was classified on the basis of results of an ELISA
      or combined ELISA and fecal culture results. Thirteen sampling schemes designed
      to randomly sample cows on the basis of lactation number, stage of lactation, and
      milk production were evaluated. Sampling without replacement was used to obtain a
      probability of herd detection of paratuberculosis for each evaluated sampling
      method and for simulated sample sizes between 30 and 150 cows. Marginal cost
      effectiveness analysis was used to determine the cost increase relative to the
      increase in detection probability. RESULTS: Sampling cows in the third or higher
      lactation and > or = 200 days into lactation yielded the highest detection
      probability in most instances, resulting in a detection probability that was 1.4
      to 2.5 times that obtained by sampling 30 cows in the second or higher lactation.
      Costs of testing via the alternative method with a 95% detection probability were
      approximately dollar 300 lower in a high-prevalence herd (31%) and dollar 800
      lower in a low-prevalence herd (9%), compared with use of the reference method.
      CONCLUSIONS AND CLINICAL RELEVANCE: Detection of herds with paratuberculosis
      could be improved, and costs of testing substantially reduced by sampling
      targeted groups of cows.

PMID- 16649917
TI  - Prevalence of exposure to Salmonella spp in finishing swine marketed in Iowa.
AB  - OBJECTIVE: To describe the prevalence of antibodies against Salmonella spp in
      swine marketed in Iowa. ANIMALS: Swine marketed by 1,044 low-volume producers and
      45 high-volume producers. PROCEDURE: Samples of diaphragm muscle collected from
      swine carcasses were tested by an indirect ELISA based on lipopolysaccharides
      from Salmonella spp, in particular Salmonella serovar Typhimurium. Prevalence of
      positive results for antibodies against Salmonella spp for carcasses, lots, and
      swine for each producer was determined. Producer-level seroprevalence was used to
      classify swine from producers as having negligible, low, moderate, or widespread
      evidence of previous or historical exposure to Salmonella spp. RESULTS: From low
      volume producers, 23,609 of 25,478 (92.7%; 95% confidence interval [CI], 92.4% to
      92.9%) samples had negative results, and 1,863 (7.3%; 95% CI, 7.05% to 7.56%) had
      antibodies against Salmonella spp. Of the 6,299 lots of swine tested, 1,191
      (18.9%) contained at least 1 sample with positive results. From high-volume
      producers, 203 of 2,486 (8.1%; 95% CI, 6.8% to 9.3%) samples had antibodies
      against Salmonella spp, and 124 of 629 lots had at least 1 sample with positive
      results for antibodies against Salmonella spp. CONCLUSIONS AND CLINICAL
      RELEVANCE: Less than 10% of pigs marketed in Iowa are apparently exposed to
      Salmonella spp. Most swine marketed by low-volume producers had negligible or
      little evidence of exposure to Salmonella spp, whereas a higher percentage of
      swine marketed by high-volume producers had positive results when tested to
      detect antibodies against Salmonella spp.

PMID- 16649918
TI  - Gait abnormalities caused by selective anesthesia of the suprascapular nerve in
      horses.
AB  - OBJECTIVE: To assess gait abnormalities associated with selective anesthesia of
      the suprascapular nerve (SSN) achieved by use of perineural catheterization and
      thereby determine the function of that nerve as it relates to gait in horses.
      ANIMALS: 3 adult horses with no preexisting clinically apparent lameness at a
      walk. PROCEDURE: Each horse was anesthetized; the right SSN was exposed
      surgically for placement of a perineural catheter to permit delivery of 1 mL of
      2% mepivacaine hydrochloride. Six hours after recovery from anesthesia, each
      horse was videotaped while walking (50-step data acquisition period) before and
      after administration of mepivacaine. Videotapes were reviewed and the proportion
      of abnormal steps before and after selective SSN anesthesia was assessed. A step
      was considered abnormal if a marked amount of scapulohumeral joint instability
      (ie, lateral luxation of the proximal portion of the humerus) was observed during
      the weight-bearing phase of the stride. RESULTS: Clinically apparent gait
      dysfunction was detected in all 3 horses following perineural administration of
      the local anesthetic agent. Anesthesia of the SSN resulted in scapulohumeral
      joint instability as evidenced by consistent lateral excursion of the shoulder
      region during the weight-bearing phase of gait at a walk. The proportion of
      abnormal steps before and after SSN anesthesia was significantly different in all
      3 horses. CONCLUSIONS AND CLINICAL RELEVANCE: These data support the role of the
      SSN in shoulder joint stability in horses and define SSN dysfunction as 1
      mechanism by which the syndrome and gait dysfunction clinically referred to as
      sweeny may develop.

PMID- 16649919
TI  - Effect of exercise on activation of the p38 mitogen-activated protein kinase
      pathway, c-Jun NH2 terminal kinase, and heat shock protein 27 in equine skeletal
      muscle.
AB  - OBJECTIVE: To investigate the effects of exercise on activation of mitogen
      activated protein kinase (MAPK) signaling proteins in horses. ANIMALS: 6 young
      trained Standardbred geldings. PROCEDURE: Horses performed a 20-minute bout of
      exercise on a treadmill at 80% of maximal heart rate. Muscle biopsy specimens
      were obtained from the vastus lateralis and pectoralis descendens muscles before
      and after exercise. Amount of expression and intracellular location of
      phosphospecific MAPK pathway intermediates were determined by use of western
      blotting and immunofluorescence staining. RESULTS: Exercise resulted in a
      significant increase in phosphorylation of p38 pathway intermediates, c-Jun NH2
      terminal kinase (JNK), and heat shock protein 27 (HSP27) in the vastus lateralis
      muscle, whereas no significant changes were found in phosphorylation of
      extracellular regulated kinase. In the pectoralis descendens muscle,
      phosphorylation of p38 and HSP27 was significantly increased after exercise.
      Immunohistochemical analysis revealed fiber-type- specific locations of
      phosphorylated JNK in type 2a/b intermediate and 2b fibers and phosphorylated p38
      in type 1 fibers. Phosphorylated HSP27 was strongly increased after exercise in
      type 1 and 2a fibers. CONCLUSIONS AND CLINICAL RELEVANCE: The p38 pathway and JNK
      are activated in the vastus lateralis muscle after a single 20-minute bout of
      submaximal exercise in trained horses. Phosphorylation of HSP27 as detected in
      the study reported here is most likely induced through the p38 signaling pathway.

PMID- 16649920
TI  - Influence of electrode placement on effective field strength in the superficial
      digital flexor tendon of horses.
AB  - OBJECTIVE: To determine the relationship between the output of an electrical
      treatment device and the effective field strength in the superficial digital
      flexor tendon of horses. SAMPLE POPULATION: Cadaver horse forelimbs without
      visible defects (n = 8) and 1 live pony. PROCEDURE: Microcurrents were generated
      by a microcurrent electrical therapy device and applied in proximodistal,
      dorsopalmar, and mediolateral directions in the entire forelimbs, dissected
      tendons, and the pony with various output settings. Corresponding field strengths
      in the tendons were measured. RESULTS: A linear relationship was detected between
      current and field strength in all conditions and in all 3 directions. In
      dissected tendons, significant differences were detected among all 3 directions,
      with highest field strength in the proximodistal direction and lowest in the
      dorsopalmar direction. In the entire forelimbs, field strength in the
      proximodistal direction was significantly lower than in the mediolateral
      direction. Results in the pony were similar to those in the entire forelimbs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Electrode placement significantly affected
      field strength in the target tissue. Many surrounding structures caused
      considerable reduction of field strength in the target tissue. These factors
      should be taken into account when establishing protocols for electrical current
      based therapeutic devices if these devices are proven clinically effective.

PMID- 16649921
TI  - Use of intra-articular administration of ethyl alcohol for arthrodesis of the
      tarsometatarsal joint in healthy horses.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intra-articular administration
      of ethyl alcohol for arthrodesis of tarsometatarsal joints in horses. ANIMALS: 8
      healthy female horses without lameness or radiographic evidence of tarsal joint
      osteoarthritis. PROCEDURE: In each horse, 1 tarsometatarsal joint was treated
      with 4 mL of 70% ethyl alcohol and the opposite joint was treated with 4 mL of
      95% ethyl alcohol. Lameness examinations were performed daily for 2 weeks,
      followed by monthly evaluations for the duration of the 12-month study.
      Radiographic evaluations of both tarsi were performed 1 month after injection and
      every 3 months thereafter. Gross and histologic examinations of the tarsi were
      undertaken at completion of the study. RESULTS: Horses had minimal to no lameness
      associated with the treatments. Radiography revealed that 8 of 16 joints were
      fused by 4 months after treatment, with significantly more joints fused in the
      70% ethyl alcohol group. Fifteen of 16 joints were considered fused at postmortem
      examination at 12 months. Gross and histologic examinations revealed foci of
      dense mature osteonal bone spanning the joint spaces. Bony fusion appeared to be
      concentrated on the dorsolateral, centrolateral, and plantarolateral aspects of
      the joints. Significant differences were not detected between treatment groups
      for lameness or pathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of ethyl alcohol into the tarsometatarsal joint of healthy horses
      appeared to facilitate arthrodesis of the joint in a pain-free manner. Results
      warrant further investigation into the potential use of ethyl alcohol in horses
      clinically affected with osteoarthritis of the tarsometatarsal and distal
      intertarsal joints.

PMID- 16649922
TI  - Association between findings on palmarodorsal radiographic images and detection
      of a fracture in the proximal sesamoid bones of forelimbs obtained from cadavers
      of racing Thoroughbreds.
AB  - OBJECTIVE: To determine the distribution for limbs and bones in horses with
      fractures of the proximal sesamoid bones and relationships with findings on
      palmarodorsal radiographic images. SAMPLE POPULATION: Proximal sesamoid bones
      obtained from both forelimbs of cadavers of 328 racing Thoroughbreds. PROCEDURE:
      Osteophytes; large vascular channels; and fracture location, orientation,
      configuration, and margin distinctness were categorized by use of high-detail
      contact palmarodorsal radiographs. Distributions of findings were determined.
      Relationships between radiographic findings and fracture characteristics were
      examined by use of chi2 and logistic regression techniques. RESULTS: Fractures
      were detected in 136 (41.5%) horses. Biaxial fractures were evident in 109 (80%)
      horses with a fracture. Osteophytes and large vascular channels were evident in
      266 (81%) and 325 (99%) horses, respectively. Medial bones typically had complete
      transverse or split transverse simple fractures, indistinct fracture margins, > 1
      vascular channel that was > 1 mm in width, and osteophytes in abaxial wing and
      basilar middle or basilar abaxial locations. Lateral bones typically had an
      oblique fracture and distinct fracture margins. Odds of proximal sesamoid bone
      fracture were approximately 2 to 5 times higher in bones without radiographic
      evidence of osteophytes or large vascular channels, respectively. CONCLUSIONS AND
      CLINICAL RELEVANCE: Biaxial fractures of proximal sesamoid bones were common in
      cadavers of racing Thoroughbreds. Differences between medial and lateral bones
      for characteristics associated with fracture may relate to differences in
      fracture pathogeneses for these bones. Osteophytes and vascular channels were
      common findings; however, fractures were less likely to occur in bones with these
      features.

PMID- 16649923
TI  - Indirect fluorescent antibody testing of cerebrospinal fluid for diagnosis of
      equine protozoal myeloencephalitis.
AB  - OBJECTIVE: To assess the use of CSF testing with an indirect fluorescent antibody
      test (IFAT) for diagnosis of equine protozoal myeloencephalitis (EPM) caused by
      Sarcocystis neurona. SAMPLE POPULATION: Test results of 428 serum and 355 CSF
      samples from 182 naturally exposed, experimentally infected, or vaccinated
      horses. PROCEDURE: EPM was diagnosed on the basis of histologic examination of
      the CNS. Probability distributions were fitted to serum IFAT results in the EPM+
      and EPM-horses, and correlation between serum and CSF results was modeled. Pairs
      of serum-CSF titers were generated by simulation, and titer-specific likelihood
      ratios and post-test probabilities of EPM at various pretest probability values
      were estimated. Post-test probabilities were compared for use of a serum-CSF test
      combination, a serum test only, and a CSF test only. RESULTS: Post-test
      probabilities of EPM increased as IFAT serum and CSF titers increased. Post-test
      probability differences for use of a serum-CSF combination and a serum test only
      were < or = 19% in 95% of simulations. The largest increases occurred when serum
      titers were from 40 to 160 and pre-test probabilities were from 5% to 60%. In all
      simulations, the difference between pre- and post-test probabilities was greater
      for a CSF test only, compared with a serum test only. CONCLUSIONS AND CLINICAL
      RELEVANCE: CSF testing after a serum test has limited usefulness in the diagnosis
      of EPM. A CSF test alone might be used when CSF is required for other procedures.
      Ruling out other causes of neurologic disease reduces the necessity of additional
      EPM testing.

PMID- 16649924
TI  - Evaluation of a comparative pathogenesis between cancer-associated retinopathy in
      humans and sudden acquired retinal degeneration syndrome in dogs via diagnostic
      imaging and western blot analysis.
AB  - OBJECTIVE: To evaluate dogs with sudden acquired retinal degeneration syndrome
      (SARDS) for evidence of pituitary gland, adrenal gland, and pulmonary neoplasia
      and antiretinal antibodies and to evaluate dogs with neoplasia for antiretinal
      antibodies. ANIMALS: 57 clinically normal dogs, 17 with SARDS, and 53 with
      neoplasia. PROCEDURE: Thoracic radiography, ultrasonography of adrenal glands,
      and contrast-enhanced computed tomography of pituitary glands were performed in
      15 dogs with SARDS. Western blot analysis was performed on sera of all dogs;
      recoverin (23 kd) and arrestin (48 kd) retinal antibodies were used as positive
      controls. RESULTS: Neoplasia was not detected via diagnostic imaging in dogs with
      SARDS. Western blot analysis revealed bands in all dogs ranging from > 48 to < 23
      kd. Prominent bands with equivalent or greater density than 1 or both positive
      controls at the 1:1,000 dilution, and present at the 1:3,000 dilution, were
      detected in 28% of clinically normal dogs, 40% of dogs with neoplasia, and 41% of
      dogs with SARDS. No bands in dogs with SARDS had a consistent location of immune
      activity, and none were detected at the 23-kd site. The area around the 48-kd
      site had increased immune activity in all 3 groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: The etiology of SARDS in dogs does not appear to be similar to cancer
      associated retinopathy in humans on the basis of absence of differential antibody
      activity against retinal proteins. Although dogs with SARDS often have clinical
      signs compatible with hyperadrenocorticism, neoplasia of the adrenal glands,
      pituitary gland, or lungs was not detected.

PMID- 16649925
TI  - Quantitative assessment of nociceptive processes in conscious dogs by use of the
      nociceptive withdrawal reflex.
AB  - OBJECTIVE: To investigate the feasibility of evoking the nociceptive withdrawal
      reflex (NWR) from fore and hind limbs in conscious dogs, score stimulus
      associated behavioral responses, and assess the canine NWR response to
      suprathreshold stimulations. ANIMALS: 8 adult Beagles. PROCEDURE: Surface
      electromyograms evoked by transcutaneous electrical stimulation of ulnaris and
      digital plantar nerves were recorded from the deltoideus, cleidobrachialis,
      biceps femoris, and tibialis cranialis muscles. Train-of-five pulses
      (stimulus(train)) were used; reflex threshold (I(t train)) was determined, and
      recruitment curves were obtained at 1.2, 1.5, and 2 x I(t train). Additionally, a
      single pulse (stimulus(single)) was given at 1, 1.2, 1.5, 2, and 3 x I(t train).
      Latency and amplitude of NWRs were analyzed. Severity of behavioral reactions was
      subjectively scored. RESULTS: Fore- and hind limb I(t train) values (median; 25%
      to 75% interquartile range) were 2.5 mA (2.0 to 3.6 mA) and 2.1 mA (1.7 to 2.9
      mA), respectively. At I(t train), NWR latencies in the deltoideus,
      cleidobrachialis, biceps femoris, and cranial tibialis muscles were not
      significantly different (19.6 milliseconds [17.1 to 20.5 milliseconds], 19.5
      milliseconds [18.1 to 20.7 milliseconds], 20.5 milliseconds [14.7 to 26.4
      milliseconds], and 24.4 milliseconds [17.1 to 40.5 milliseconds], respectively).
      Latencies obtained with stimulus(train) and stimulus(single) were similar. With
      increasing stimulation intensities, NWR amplitude increased and correlated
      positively with behavioral scores. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs,
      the NWR can be evoked from limbs and correlates with behavioral reactions.
      Results suggest that NWR evaluation may enable quantification of nociceptive
      system excitability and efficacy of analgesics in individual dogs.

PMID- 16649926
TI  - Evaluation of the prevalence and onset of lung lesions and their impact on growth
      of lambs.
AB  - OBJECTIVE: To determine the prevalence and temporal onset of lung lesions in
      lambs and the impact of lung lesions on growth of affected lambs. ANIMALS: 259
      crossbred wether lambs from a single flock in the upper Midwestern United States.
      PROCEDURE: An observational study was conducted. Lambs born in the spring and
      fall were slaughtered at finished weight or at a predetermined time point. Lungs
      of each lamb were examined and classified as normal, moderate lesions
      (consolidation > 5% but < or = 50% of any lobe), or severe lesions (consolidation
      > 50% of any lobe). Data were examined to detect effects of prevalence or
      severity of lung lesions on growth and carcass traits. RESULTS: 57 of 89 (64%)
      spring-born lambs had lung lesions characterized by consolidation of lung tissue.
      A small number of lambs had pulmonary adhesions or active abscesses. In contrast,
      only 31 of 108 (29%) fall-born lambs had lung lesions. Severe lung lesions were
      associated with a significant reduction in average daily gain. Severe lung
      lesions were not detected until the middle of the finishing period and were
      associated with culture of Mannheimia haemolytica or Pasteurella multocida.
      CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results indicates that the
      prevalence of severe lung lesions can be quite high in lambs. Severe lung lesions
      can lead to greatly decreased growth performance of lambs.

PMID- 16649927
TI  - Effect of diameter of the drill hole on torque of screw insertion and pushout
      strength for headless tapered compression screws in simulated fractures of the
      lateral condyle of the equine third metacarpal bone.
AB  - OBJECTIVE: To compare variables for screw insertion, pushout strength, and
      failure modes for a headless tapered compression screw inserted in standard and
      oversize holes in a simulated lateral condylar fracture model. SAMPLE POPULATION:
      6 pairs of third metacarpal bones from horse cadavers. PROCEDURE: Simulated
      lateral condylar fractures were created, reduced, and stabilized with a headless
      tapered compression screw by use of a standard or oversize hole. Torque, work,
      and time for drilling, tapping, and screw insertion were measured during site
      preparation and screw implantation. Axial load and displacement were measured
      during screw pushout. Effects of drill hole size on variables for screw insertion
      and screw pushout were assessed by use of Wilcoxon tests. RESULTS: Drill time was
      59% greater for oversize holes than for standard holes. Variables for tapping
      (mean maximum torque, total work, positive work, and time) were 42%, 70%, 73%,
      and 58% less, respectively, for oversize holes, compared with standard holes.
      Variables for screw pushout testing (mean yield load, failure load, failure
      displacement, and failure energy) were 40%, 40%, 47%, and 71% less, respectively,
      for oversize holes, compared with standard holes. Screws could not be completely
      inserted in 1 standard and 2 oversize holes. CONCLUSIONS AND CLINICAL RELEVANCE:
      Enlarging the diameter of the drill hole facilitated tapping but decreased
      overall holding strength of screws. Therefore, holes with a standard diameter are
      recommended for implantation of variable pitch screws whenever possible. During
      implantation, care should be taken to ensure that screw threads follow tapped
      bone threads.

PMID- 16649928
TI  - Urodynamic and morphologic changes in the lower portion of the urogenital tract
      after administration of estriol alone and in combination with phenylpropanolamine
      in sexually intact and spayed female dogs.
AB  - OBJECTIVE: To compare the urodynamic and morphologic effects of the
      administration of estriol alone and in combination with phenylpropanolamine on
      the lower portion of the urogenital tract in female dogs. ANIMALS: 3 sexually
      intact and 3 spayed female Beagles without urinary incontinence. PROCEDURE: Dogs
      received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO)
      and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure
      profilometry, diuresis cystometry, and vaginourethrography were performed before
      treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and
      closure pressure (MUCP), urethral functional and anatomic profile lengths,
      integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure,
      threshold pressure, threshold volume, compliance, urethral length, and vaginal
      length and width were measured. RESULTS: Before treatment, no urodynamic
      differences were observed between the 2 groups; however, vaginal length and width
      were significantly shorter in spayed dogs. Compared with day 0 values, estriol
      treatment significantly increased MUP, MUCP, and IP values at day 7, but at day
      14, this effect decreased despite phenylpropanolamine administration. No
      morphologic changes from baseline were detected after either treatment in any
      dog. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that estriol mainly acts on
      the urethral sphincter mechanism by increasing urethral resistance in sexually
      intact and spayed female dogs without urinary incontinence. Administration of
      estriol and phenylpropanolamine did not increase the urethral resistance more
      than estriol alone. The urodynamic effects of estriol in female dogs with urinary
      incontinence remain to be elucidated.

PMID- 16649929
TI  - Genetic basis of secondary osteoarthritis in dogs with joint dysplasia.

PMID- 16649931
TI  - Swine veterinarians resolve to eliminate the PRRS virus.

PMID- 16649932
TI  - Comments on the Preservation of Antibiotics Act.

PMID- 16649933
TI  - What is your diagnosis? Pyloric-duodenal intussusception.

PMID- 16649934
TI  - What is your diagnosis? Primary lung tumor.

PMID- 16649935
TI  - Diagnostic imaging in veterinary dental practice. Ameloblastoma.

PMID- 16649936
TI  - Impact of bluetongue virus infection on the international movement and trade of
      ruminants.

PMID- 16649937
TI  - Effects of electrostimulated acupuncture on ground reaction forces and pain
      scores in dogs with chronic elbow joint arthritis.
AB  - OBJECTIVE: To determine whether use of electrostimuluated acupuncture (ESA) would
      result in significant improvements in ground reaction forces and lameness scores
      in dogs with chronic elbow joint osteoarthritis secondary to elbow joint
      dysplasia. DESIGN: Randomized, controlled, crossover clinical trial. ANIMALS: 9
      dogs with chronic forelimb lameness and radiographic evidence of elbow joint
      osteoarthritis. PROCEDURES: All dogs had a 3-week control acclimation period
      during which gait analysis was performed weekly. Dogs then received ESA once
      weekly for 3 weeks followed by a sham treatment once weekly for 3 weeks or
      received the sham treatment followed by ESA. Gait analysis was repeated prior to
      each treatment, and owners were asked to provide pain scores by use of a visual
      analog scale method. RESULTS: Treatment (control, acupuncture, or sham) did not
      have a significant effect on ground reaction forces for any limb. Owners of 8 of
      the 9 dogs were able to correctly guess the time period when ESA was delivered.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESA did not have any
      significant effects on severity of lameness, as determined by measurement of
      ground reaction forces, or severity of pain, as determined by visual analog scale
      pain scores, in dogs with chronic elbow joint osteoarthritis secondary to elbow
      joint dysplasia.

PMID- 16649938
TI  - Evaluation of cellophane banding with and without intraoperative attenuation for
      treatment of congenital extrahepatic portosystemic shunts in dogs.
AB  - OBJECTIVE: To evaluate the effect of intraoperative attenuation of congenital
      extrahepatic portosystemic shunts (CEPSSs) during cellophane banding procedures
      in dogs. STUDY DESIGN: Retrospective case series and prospective study. ANIMALS:
      18 cases evaluated retrospectively and 14 dogs evaluated prospectively.
      PROCEDURES: Gradual occlusion of CEPSSs was performed via cellophane banding.
      Shunts were occluded to a diameter < 3.0 mm during surgery in dogs prospectively
      enrolled in the partial attenuation group, whereas the shunt was not attenuated
      during surgery in dogs prospectively enrolled in the no-attenuation group or in
      dogs that had previously undergone surgery and were retrospectively evaluated.
      Postprandial serum bile acids (PPSBA) concentrations were measured before surgery
      and at various time points after surgery. RESULTS: Mean +/- SD PPSBA
      concentrations were 26.8 +/- 24.5 micromol/L at < 2.25 months after surgery (n =
      16 dogs), 22.1 +/- 14.0 micromol/L from 2.25 to 6 months after surgery (12 dogs),
      and 34.9 +/- 32.5 micromol/L at > 6 months after surgery (22 dogs). In the
      prospectively enrolled dogs, mean PPSBA concentrations increased over time in
      dogs in the partial attenuation group, but not in dogs in the no-attenuation
      group. CONCLUSIONS AND CLINICAL RELEVANCE: Cellophane banding may be used to
      occlude larger CEPSSs and may decrease the need for intraoperative monitoring of
      portal vein blood pressure. The technique may facilitate minimally invasive
      treatment of CEPSSs in dogs. Intraoperative attenuation of CEPSSs to a diameter <
      3.0 mm is not necessary and may result in a less favorable outcome.

PMID- 16649939
TI  - Ultrasonographic and color-flow Doppler ultrasonographic assessment of direct
      cutaneous arteries used for axial pattern skin flaps in dogs.
AB  - OBJECTIVE: To describe a method for ultrasonographic and color-flow Doppler
      ultrasonographic imaging of the 4 direct cutaneous arteries commonly used for
      axial pattern skin flaps in dogs. DESIGN: Descriptive report. ANIMALS: 20
      clinically normal dogs. PROCEDURES: Dogs were manually restrained and fundamental
      and harmonic ultrasonographic and color-flow Doppler ultrasonographic
      examinations of the superficial cervical, thoracodorsal, deep circumflex iliac
      (cranial and caudal branches), and caudal superficial epigastric arteries were
      performed by a resident in diagnostic imaging. The level of confidence in
      locating these vessels was subjectively graded as high, moderate, or low.
      RESULTS: High-frequency fundamental and harmonic ultrasonography was important
      for maximizing image resolution, and color-flow Doppler ultrasonography was
      important for vessel identification. The superficial cervical artery was the most
      difficult vessel to identify; confidence in correct vessel identification was low
      or moderate. The thoracodorsal and deep circumflex iliac arteries were identified
      with a moderate or high level of confidence. The caudal superficial epigastric
      artery was the easiest vessel to identify; confidence in correct vessel
      identification was high. Except for the superficial cervical artery, the level of
      confidence in correct vessel identification improved over time as operator
      experience increased. CONCLUSION AND CLINICAL RELEVANCE: Results suggest that the
      combination of fundamental ultrasonographic and color-flow Doppler
      ultrasonographic imaging is an easy and noninvasive method for identifying the 4
      direct cutaneous arteries commonly used for axial pattern skin flaps in dogs.
      This method could be useful in planning axial pattern skin flaps, particularly in
      dogs with regional soft tissue trauma in which the integrity of the vessel is in
      question.

PMID- 16649940
TI  - Hypertrophic osteopathy associated with pulmonary Eikenella corrodens infection
      in a dog.
AB  - CASE DESCRIPTION: A 4-year-old English Pointer was examined because of chronic,
      progressive signs of pulmonary disease and failure to respond to medical
      treatment. CLINICAL FINDINGS: At examination, radiography of the thorax revealed
      increased pulmonary opacity and air bronchograms in the right caudal lung lobe,
      and radiography of the forelimbs revealed periosteal bone production typical of
      hypertrophic osteopathy. Attempts to isolate a causative organism included
      bacterial culture of bronchoalveolar lavage fluid and a lung tissue specimen
      obtained via fine-needle aspiration. Despite a cytologic diagnosis of septic
      suppurative inflammation in the lavage fluid, those specimens did not yield
      bacterial growth. However, a biopsy specimen obtained during a lung lobectomy
      procedure yielded growth of Eikenella corrodens. TREATMENT AND OUTCOME: Despite
      successful surgical removal of the consolidated lung lobe and initiation of
      antimicrobial treatment, the dog died 6 days after surgery. CLINICAL RELEVANCE:
      The authors are not aware of reports of pulmonary infection with E. corrodens in
      animals. Infection with the organism is rare, but it is possible that infections
      are underreported given that the organism is difficult to culture and biopsy may
      be necessary to obtain enough tissue to yield a diagnosis.

PMID- 16649941
TI  - Clinical signs and results of treatment in cats with patellar luxation: 42 cases
      (1992-2002).
AB  - OBJECTIVE: To describe clinical signs and results of treatment in cats with
      patellar luxation. DESIGN: Retrospective case series. ANIMALS: 42 cats in which
      patellar luxation had been diagnosed on the basis of results of palpation of the
      stifle joints. PROCEDURES: Degree of luxation was graded on a scale from 1 to 4,
      and severity of lameness was graded on a scale from 0 to 5. Radiographs of stifle
      joints were evaluated for signs of osteoarthritis. Long-term function was
      classified as poor, fair, good, or excellent. RESULTS: 34 cats had bilateral
      luxation and 8 had unilateral luxation. Only 7 (17%) cats had a history of
      trauma. Mean age of the cats was 3.3 years, and mean weight was 4.26 kg (9.4 lb);
      26 (62%) were domestic shorthairs. Seventy-three of the 76 (95%) affected joints
      had medial patellar luxation. Luxation grades could be assigned to 65 joints,
      with grade 2 (30 joints) and 3 (22 joints) luxation being most common. Lameness
      grades could be assigned to 73 joints, with grade 1 lameness (27 joints) most
      common. Outcome was excellent for 8 of 17 joints treated without surgery and for
      23 of 35 joints treated surgically. Complications attributable to surgery were
      reported in 8 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Patellar luxation should
      be considered as a cause of hind limb lameness in cats. Low-grade luxation can be
      associated with lameness of the same severity as high-grade luxation. Surgical
      correction of patellar luxation in cats with grade 2 or 3 lameness can result in
      a favorable outcome.

PMID- 16649942
TI  - Cholecystoenterostomy for treatment of extrahepatic biliary tract obstruction in
      cats: 22 cases (1994-2003).
AB  - OBJECTIVE: To identify factors associated with outcome in cats with extrahepatic
      biliary tract obstruction (EHBTO) that undergo biliary diversion surgery. DESIGN:
      Retrospective case series. ANIMALS: 22 cats. PROCEDURES: Medical records of cats
      with surgically confirmed EHBTO that underwent cholecystoenterostomy were
      reviewed. RESULTS: Clinical signs and physical examination findings included
      vomiting, anorexia, icterus, lethargy, weakness, and weight loss. Common
      clinicopathologic abnormalities included high serum hepatic enzyme activities and
      serum bilirubin concentration. Abdominal ultrasonography was performed in 21
      cats, and all 21 had findings consistent with EHBTO. Eleven of 15 cats in which
      blood pressure was monitored had intraoperative hypotension. Eighteen cats had
      anemia following surgery, and 14 cats had persistent hypotension. Extrahepatic
      biliary tract obstruction was a result of neoplasia in 9 cats and chronic
      inflammatory disease in 13. Fourteen cats survived long enough to be discharged
      from the hospital, but only 6 survived > 6 months after surgery, all of which had
      chronic inflammatory disease. Median survival time for cats with neoplasia (14
      days) was significantly shorter than that for cats with inflammatory disease (255
      days). No other variable was associated with outcome. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that cats with EHBTO secondary to neoplasia have a
      poorer prognosis than cats with EHBTO secondary to chronic inflammatory disease.
      However, the overall prognosis for cats with EHBTO undergoing
      cholecystoenterostomy must be considered guarded to poor, and the incidence of
      perioperative complications is high.

PMID- 16649943
TI  - Physical characteristics, blood hormone concentrations, and plasma lipid
      concentrations in obese horses with insulin resistance.
AB  - OBJECTIVE: To compare obese horses with insulin resistance (IR) with nonobese
      horses and determine whether blood resting glucose, insulin, leptin, and lipid
      concentrations differed between groups and were correlated with combined glucose
      insulin test (CGIT) results. ANIMALS: 7 obese adult horses with IR (OB-IR group)
      and 5 nonobese mares. PROCEDURES: Physical measurements were taken, and blood
      samples were collected after horses had acclimated to the hospital for 3 days.
      Response to insulin was assessed by use of the CGIT, and maintenance of plasma
      glucose concentrations greater than the preinjection value for > or = 45 minutes
      was used to define IR. Area under the curve values for glucose (AUC(g)) and
      insulin (AUC(i)) concentrations were calculated. RESULTS: Morgan, Paso Fino,
      Quarter Horse, and Tennessee Walking Horse breeds were represented in the OB-IR
      group. Mean neck circumference and BCS differed significantly between groups and
      were positively correlated with AUC values. Resting insulin and leptin
      concentrations were 6 and 14 times as high, respectively, in the OB-IR group,
      compared with the nonobese group, and were significantly correlated with AUC(g)
      and AUC(i). Plasma nonesterified fatty acid, very low-density lipoprotein, and
      high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly
      higher (86%, 104%, and 29%, respectively) in OB-IR horses, and HDL-C
      concentrations were positively correlated with AUC values. CONCLUSIONS AND
      CLINICAL RELEVANCE: Measurements of neck circumference and resting insulin and
      leptin concentrations can be used to screen obese horses for IR. Dyslipidemia is
      associated with IR in obese horses.

PMID- 16649945
TI  - Effectiveness of using a mat filled with a peroxygen disinfectant to minimize
      shoe sole contamination in a veterinary hospital.
AB  - OBJECTIVE: To determine the effectiveness of using a disinfectant mat filled with
      a peroxygen compound to prevent mechanical transmission of bacteria via
      contaminated footwear between the food animal ward and common breezeway of a
      veterinary teaching hospital. DESIGN: Observational study. SAMPLE POPULATION:
      Shoe soles of individuals entering and exiting from the ward. PROCEDURES: A mat
      filled with peroxygen disinfectant was placed at the entrance to the food animal
      ward, and participants wiped each shoe twice on the mat surface (n = 16) or
      walked on the mat surface but did not wipe their shoes (17) before entering and
      exiting from the ward. Swab specimens were collected from the shoe soles of
      participants before and after mat use and submitted for bacterial culture.
      RESULTS: For both study days, as participants entered the ward, median number of
      aerobic bacteria isolated from shoe swab specimens collected prior to use of the
      disinfectant mat was not significantly different from median number isolated
      after use of the disinfectant mat. However, as participants exited the ward,
      median number of aerobic bacteria isolated from shoe swab specimens collected
      prior to use of the disinfectant mat was significantly higher than median number
      isolated after use of the disinfectant mat. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that placing a mat filled with a peroxygen disinfectant at the
      exit from the food animal ward of a veterinary teaching hospital may help reduce
      mechanical transmission of bacteria on the footwear of individuals leaving the
      ward.

PMID- 16649947
TI  - Noise in the animal shelter environment: building design and the effects of daily
      noise exposure.
AB  - Sound levels in animal shelters regularly exceed 100 dB. Noise is a physical
      stressor on animals that can lead to behavioral, physiological, and anatomical
      responses. There are currently no policies regulating noise levels in dog
      kennels. The objective of this study was to evaluate the noise levels dogs are
      exposed to in an animal shelter on a continuous basis and to determine the need,
      if any, for noise regulations. Noise levels at a newly constructed animal shelter
      were measured using a noise dosimeter in all indoor dog-holding areas. These
      holding areas included large dog adoptable, large dog stray, small dog adoptable,
      small dog stray, and front intake. The noise level was highest in the large
      adoptable area. Sound from the large adoptable area affected some of the noise
      measurements for the other rooms. Peak noise levels regularly exceeded the
      measuring capability of the dosimeter (118.9 dBA). Often, in new facility design,
      there is little attention paid to noise abatement, despite the evidence that
      noise causes physical and psychological stress on dogs. To meet their behavioral
      and physical needs, kennel design should also address optimal sound range.

PMID- 16649948
TI  - Effects of induced molting on the well-being of egg-laying hens.
AB  - Induced molting in egg-laying hens is an important method for maximizing hen egg
      production and quality as well as hen health in commercial settings; however,
      there is growing societal concern over its effects on hen well-being. Using
      individual hens as their own controls, this research examined the behavior of
      hens subjected to different treatments of induced molting under premolt, molt,
      and postmolt conditions. Cage pecking increased in fast-induced subjects and
      aggression increased in fast-induced and nonfast-induced subjects during the
      molt. Gakel calling and several aspects of its acoustic structure were much
      higher during the molt condition in fast-induced subjects only. These data
      suggest that nonfast-induced molting treatments provide an effective method for
      inducing molting in hens and improving their well-being by minimizing discomfort
      due to food deprivation. In addition, these data further support that gakel
      vocalizations in hens may serve as an effective indicator for assessing well
      being in a species otherwise behaviorally stoic in expressing stress or
      discomfort.

PMID- 16649949
TI  - Conditioning shelter dogs to sit.
AB  - Human contact in the shelter may lessen effects of change in environment and
      smooth transition into a home. Training can increase a dog's interaction with
      people in a shelter environment. Experiments were conducted to determine how
      rapidly shelter dogs learn to sit, if the dogs can retain sitting behavior over
      time, and if sitting transfers to novel locations and people. Two experiments
      trained shelter dogs (n = 21) to sit when a stranger approached over a 10-trial
      session. Food and a verbal cue or a clicker reinforced the sit. The experiments
      measured latency to sit for each trial. Latency to sit decreased significantly
      over trials. Another experiment included reinforcement given to dogs (n = 20) on
      a noncontingent basis or for sitting. Five days of the experiment (condition
      training) were in the same room with the same experimenter. The last 4 days
      (testing) varied by both experimenter and location (familiar or strange). Results
      indicate that short training sessions are effective for teaching shelter dogs to
      sit, that dogs can retain sitting behavior over 2 days, and that training
      transfers to novel people and situations.

PMID- 16649950
TI  - Effect of diet change on the behavior of chicks of an egg-laying strain.
AB  - Injurious pecking has serious welfare consequences in flocks of hens kept for egg
      laying, especially when loose-housed. Frequent diet change is a significant risk
      for injurious pecking; how the mechanics of diet change influence pecking
      behavior is unknown. This study investigated the effect of diet change on the
      behavior of chicks from a laying strain. The study included a 3-week familiarity
      phase: 18 chick pairs received unflavored feed (Experiment 1); 18 pairs received
      orange oil-flavored (Experiment 2). All chicks participated in a dietary
      preference test (P); a diet change (DC); or a control group (C), 6 scenarios. All
      P chicks preferred unflavored feed. In Experiment 1, DC involved change from
      unflavored to orange-flavored; Experiment 2, orange- flavored to unflavored.
      Compared with controls, Experiment 2 DC chicks exhibited few behavioral
      differences; Experiment 1 DC chicks exhibited increased behavioral event rates on
      Days 1 and 7. They pecked significantly longer at their environment; by Day 7,
      they showed significantly more beak activity. There was little evidence of
      dietary neophobia. Change from more preferred to less preferred feed led to
      increased activity and redirected pecking behavior.

PMID- 16649951
TI  - A nonnatural head-neck position (Rollkur) during training results in less acute
      stress in elite, trained, dressage horses.
AB  - This study measured parameters of stress in recreational, trained horses (REC; n
      = 7) and elite (International Grand Prix level) trained, dressage horses (DRES; n
      = 5). The training of the DRES horses uses an unnatural head-neck position
      (Rollkur), whereas in the REC horses such training techniques are not common. The
      study measured stress by using heart rate variability analysis for 30 min
      postfeeding in the morning and 30 min postexercise after a morning training
      session. The study found no significant difference at rest between the REC and
      DRES horses. During the posttraining measurements, however, the DRES horses
      showed, among others, a less sympathetic and increased parasympathetic dominance.
      These results suggest that DRES horses tend to have less acute stress than do REC
      horses postexercise. The findings of this study suggest maintaining the health
      and well-being of DRES horses despite nonnatural, biomechanical positions.

PMID- 16649952
TI  - Behavioral management at the Phoenix Zoo: new strategies and perspectives.
AB  - It all started with a seemingly simple decision to re-evaluate and document the
      Phoenix Zoo's behavioral management protocol. The purpose of this project was to
      present proactive standards for the care and psychological well-being of our
      living collection, while meeting or exceeding the guidelines of the Animal
      Welfare Act (U. S. Department of Agriculture Animal and Plant Health and
      Inspection Service, Animal Care, 1999). Preparing the protocol was a catalyst to
      re-evaluate the zoo's philosophy and application of behavioral management. It
      suggested a restructuring of collection management and the rethinking of future
      goals and practices. Gradually, the process became more focused and organized.
      Behavioral enrichment, training, animal behavior issues, and exhibit architecture
      were embraced as essential components for providing quality of life. Staff from
      all levels worked side-by-side on assignments. Our way of thinking and working
      was changing.

PMID- 16649953
TI  - Impact of a bilingual mobile spay/neuter clinic in a U.S./Mexico border city.
AB  - There are between 4 and 10 million dogs and cats killed annually in the United
      States. Although there are no accurate national estimates of the number of
      companion animals who are sterilized surgically. Approximately 26,000 companion
      animals are euthanized annually in El Paso County, Texas, located on the
      U.S./Mexico border. In an effort to determine if a readily available spay/neuter
      program would be cost effective and eventually help to lower the county's
      euthanasia rate, a mobile spay/neuter clinic began operation for a 5-month period
      in 2004, using a volunteer veterinarian and paid staff. Sterilizations performed
      totaled 1,108: 959 dogs (372 males and 587 females) and 149 cats (50 males and 99
      females). The per companion animal sterilization cost of 15.13 dollars (27.83
      dollars had the veterinarian been paid) was considerably cheaper than the rate of
      57 dollars per companion animal achieved by a local voucher program contracting
      with private veterinarians to perform reduced-cost sterilizations.

PMID- 16649956
TI  - Patterns of HIV prevalence and HIV risk behaviors among injection drug users
      prior to and 24 months following implementation of cross-border HIV prevention
      interventions in northern Vietnam and southern China.
AB  - In 2002, we implemented a 4-year HIV prevention intervention for injection drug
      users (IDUs) in Lang Son Province, Vietnam, and Ning Ming County, Guangxi
      Province, China, a cross-border region seriously affected by inter-twined
      epidemics of heroin injection and HIV infection. The interventions involve peer
      education on HIV risk reduction and provision of new needles/syringes through
      direct distribution and pharmacy vouchers. We consider this to be a structural
      intervention in which risk reduction information and sterile injection equipment
      are diffused through the IDU populations and not limited to those who actually
      interact with peer educators. The evaluation of structural interventions poses
      complex methodological challenges. The evaluation of our interventions relies
      primarily on cross-sectional surveys (interviews and HIV testing) of samples of
      IDUs selected using a combination of targeted cluster and snowball methods. We
      consider this to be an appropriate, albeit imperfect, design given the study
      context. This paper presents analyses of data from the IDU surveys conducted just
      prior to implementation of the interventions and 24 months thereafter. The cross
      border interventions have reached large proportions of the IDUs in the project
      sites, drug-related HIV risk behaviors have declined in frequency, and HIV
      prevalence among IDUs has been stable in China and declined in Vietnam over the
      24 months since the interventions were implemented. Attribution of these positive
      trends to the interventions must be qualified in light of possible sampling
      biases and the absence of control groups. However, we believe that the structural
      interventions implemented by the cross-border project have played a role in
      stabilizing HIV prevalence among IDUs two years after they were initiated.
      Evidence of further diffusion of the interventions among IDUs and continued
      stability or decline of HIV prevalence would strengthen this case.

PMID- 16649957
TI  - Marketing the 'Sex Check': evaluating recruitment strategies for a telephone
      based HIV prevention project for gay and bisexual men.
AB  - Designing effective marketing and recruitment strategies for HIV prevention
      research requires attention to cultural relevance, logistical barriers, and
      perceived psychosocial barriers to accessing services. McGuire's
      communication/persuasion matrix (1985) guided our evaluation, with particular
      attention to success of each marketing "channel" (i.e., strategy) vis-a-vis the
      number of all callers, eligible callers, and enrolled callers, as well as
      reaching so-called "hard-to-serve" individuals. Nearly all channels offered
      success in reaching specific subgroups. Latinos responded favorably to posters,
      bisexuals responded favorably to paid media in an alternative (non-gay)
      publication, and precontemplators responded to referrals by family and friends.
      Although multiple recruitment strategies were used, three were crucial to the
      success of the project: (a) recruiters' presence in gay venues, (b) referrals by
      family and friends (snowball technique), and (c) paid advertisements in
      alternative (non-gay) local newspapers. Resource allocation and costs are also
      presented for each channel.

PMID- 16649958
TI  - Gay men's report of regret of HIV disclosure to family, friends, and sex
      partners.
AB  - The purpose of this study was to examine whether HIV-positive MSM experience
      regret as a consequence of disclosing their HIV serostatus. Participants for this
      study were 76 HIV-positive MSM involved in a longitudinal study of HIV disclosure
      (N = 139). Men with at least one network member that was aware of his HIV
      infection were included in the analyses. Results revealed that overall, HIV
      positive men do not regret family or friends knowing about their serostatus
      (63%). The observed proportion of regret events was practically negligible
      (4.2%). Compared with friends, the odds of experiencing regret were greater in
      the immediate family, with coworkers, and casual sex partners but was not
      significantly different in the extended family or committed sex partners. Despite
      disclosure being regarded as an anxiety provoking activity and negative reactions
      are typically anticipated, HIV disclosure appears to elicit very little regret to
      a wide variety of social network members. Furthermore, there were no differences
      in the occurrence of regret whether the HIV-positive person disclosed personally
      or if someone else disclosed for them. In both instances regret was remarkably
      low.

PMID- 16649959
TI  - Positive, negative, unknown: assumptions of HIV status among HIV-positive men who
      have sex with men.
AB  - Serosorting (i.e., engaging in unprotected sex with partners known to be of the
      same serostatus) can be a difficult process for men who have sex with men (MSM)
      who frequently make assumptions about their partners' serostatus. This process
      can be further complicated by a partner's dishonesty as well as other individual
      and contextual factors. The present study specifically examined how assumptions
      of serostatus made about unknown serostatus partners impact on the sexual
      behavior of 110 alcohol-abusing HIV-positive MSM. Although previous research has
      shown that HIV-positive MSM are more likely to serosort with other known HIV
      positive men than with known HIV-negative men, our data suggest that unprotected
      sex behavior may not be specifically driven by whether or not they made
      assumptions of seroconcordance or serodiscordance. The types of assumptions these
      HIV-positive MSM made about their unknown status sexual partners and the basis
      for such assumptions were also examined. Owing to the ambiguities involved in
      assumptions of a partner's serostatus in sexual encounters, the 'unknown status'
      partner category is analytically distinct from 'known status' categories, and
      needs to be more fully explored because of its impact on perceived serosorting,
      rather than actual serosorting, among HIV-positive men.

PMID- 16649960
TI  - Perceived partner serostatus, attribution of responsibility for prevention of HIV
      transmission, and sexual risk behavior with "MAIN" partner among adults living
      with HIV.
AB  - Persons living with HIV (PLH) often attribute HIV status to sexual partners based
      on observable partner characteristics. The present study investigated the
      relationship of sexual behavior with most recent "main" partner to that partner's
      perceived serostatus among 1,232 PLH interviewed in clinics and community
      agencies in Los Angeles, California. PLH who believed their most recent main
      partner to be HIV-negative more often identified partner appearance as a basis
      for their perceptions than those who believed their most recent main partner to
      be HIV-positive. PLH who perceived their most recent main partner as HIV-negative
      were more likely to assume responsibility for partner protection and always to
      use condoms, and less likely to report recent unprotected vaginal or anal sex
      with that partner. Unprotected receptive anal intercourse with their most recent
      main partner was less common among African American, Latino, and White
      participants who believed that partner to be HIV-negative. Although PLH appear
      protective toward HIV-negative main partners, interventions to encourage valid
      methods of identifying partner serostatus are needed.

PMID- 16649961
TI  - Reputationally strong HIV prevention programs: lessons from the front line.
AB  - Although HIV prevention researchers have conducted numerous controlled outcome
      studies to evaluate the effectiveness of theory-based interventions aimed at
      reducing HIV risk behaviors, many HIV risk reduction interventions are conducted
      not by researchers but by staff in local health departments or community-based
      organizations (CBOs). Despite their widely recognized role in slowing the spread
      of HIV, very few attempts have been geared toward understanding the programmatic
      and organizational characteristics of their HIV prevention efforts. The Centers
      for Disease Control and Prevention's Characteristics of Reputationally Strong
      Programs project identified and profiled 18 innovative, community-based, HIV
      prevention programs viewed by community partners as successful. The aim was to
      determine common features of the programs that could be widely applied to improve
      HIV prevention research and programs. Results indicated that several common
      intervention characteristics and organizational characteristics, including agency
      support and staff commitment, played significant roles in the success of
      reputationally strong programs.

PMID- 16649962
TI  - Sexual behavior among employed male rural migrants in Shanghai, China.
AB  - A study of sexual behavior in migrant men was conducted in construction sites,
      markets, and factories in Shanghai, the largest city in China. An anonymous, self
      administered questionnaire was completed by the migrants. Among 986 sexually
      active men, 14% had had more than one sexual partner in their lifetime, 31%
      premarital sex, 3.3% oral sex, and 11.5% commercial sex. Seventy-eight percent
      never used condoms. Risk-taking was similar in different working venues but
      increased with decreasing age. Younger men initiated sexual intercourse earlier
      and had more premarital sex and sexual partners as well as more frequent sexual
      encounters. Risk-factors that correlate with having multiple sex partners
      included having seen pornography, early age at initiating sexual intercourse,
      premarital sex, and a desire for legalization of commercial sex. Sexually
      transmitted diseases and HIV are likely to increase among migrants, particularly
      those who are young. Intervention strategies should target younger migrants, and
      must accommodate a low literacy level.

PMID- 16649963
TI  - Insulin resistance after prenatal growth restriction: is it mediated by
      adiponectin deficiency?

PMID- 16649964
TI  - Anterior pituitary dysfunction following traumatic brain injury (TBI).
AB  - Traumatic brain injury (TBI) is the commonest cause of death and disability in
      young adults living in industrialized countries. Several recent studies have
      convincingly shown that anterior hypopituitarism is a common complication of head
      trauma with a prevalence of at least 25% among long-term survivors. This is a
      much higher frequency than previously thought and suggests that most cases of
      post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. These
      findings raise important questions about the potential contribution of PTHP to
      the high physical and neuropsychiatric morbidity seen in this group of patients.
      In this review, we examine the published reports on the neuroendocrine
      abnormalities in TBI patients and highlight new data that give novel insights
      into the natural history of this disorder. We discuss the potential contribution
      of PTHP to recovery and rehabilitation after injury and the need for the
      identification and the appropriate and timely management of hormone deficiencies
      to optimize patient recovery from head trauma, improve quality of life and avoid
      the long-term adverse consequences of untreated hypopituitarism.

PMID- 16649965
TI  - Bone health in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED): findings in 25 adults.
AB  - OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is characterized by chronic mucocutaneous candidiasis and autoimmune
      destruction of endocrine organs. The resulting endocrinopathies and their
      treatment may impact bone health. The purpose of our study was to assess bone
      health and its correlates in adult patients with APECED. PATIENTS AND METHODS:
      Twenty-five adults (12 males) with APECED were prospectively assessed. Data on
      their previous medical history were collected from hospital records. Areal bone
      mineral density (aBMD) for the lumbar spine (L1-L4), femoral neck and whole body
      as well as volumetric BMD (vBMD) for the lumbar spine (L2-L4) were measured with
      dual-energy X-ray absorptiometry (DXA). RESULTS: Mean age was 34 years (range 21
      59 years). All patients had 1-4 autoimmune endocrinopathies, the most common
      being adrenocortical failure (20 patients) and hypoparathyroidism (18 patients).
      Osteopaenia or osteoporosis was present in 28%. The median (range) aBMD Z-scores
      were for the lumbar spine -0.3 (-2.3 to +3.3) and for the femoral neck, -0.1 (
      2.2 to +2.0). The BMD Z-scores tended to be higher in patients with
      hypoparathyroidism than in patients with normal parathyroid function (at the
      lumbar spine +0.4 vs.-1.2, P = 0.016, and at the femoral neck +0.3 vs.-0.4, P =
      0.090). Adrenocortical failure had a negative impact on BMD. Six patients had had
      low-impact fractures and three were diagnosed with compression fractures.
      CONCLUSIONS: Despite the complex endocrine problems, the overall prevalence of
      symptomatic osteoporosis is low in adults treated for APECED. Osteopaenia is
      frequently observed and warrants follow-up. Treated hypoparathyroidism may have a
      positive, and adrenocortical failure a negative, impact on bone health.

PMID- 16649966
TI  - No effect of B vitamins on ADMA levels in patients at increased cardiovascular
      risk.
AB  - OBJECTIVE: Asymmetric dimethylarginine (ADMA) is a recently identified potent
      cardiovascular risk factor. ADMA levels are increased in hyperhomocysteinaemia
      and the metabolism of ADMA is linked with that of homocysteine in several ways.
      Treatment with B vitamins effectively reduces homocysteine levels, but studies
      investigating the effect on ADMA levels are scarce and show conflicting results.
      In this study we evaluated the effect of treatment with B vitamins on ADMA levels
      in two high cardiovascular risk populations. METHODS: In study I, 110 siblings of
      patients with clinical atherosclerotic disease and postmethionine
      hyperhomocysteinaemia were treated with 5 mg of folic acid and 250 mg of
      pyridoxine or placebo, and were analysed after 1 year. In study II, 41 patients
      with type 2 diabetes and mild hyperhomocysteinaemia were analysed after 6 months
      treatment with 5 mg of folic acid or placebo. RESULTS: A correlation between
      baseline homocysteine and ADMA levels was found, which was partly due to
      confounding by renal function. Homocysteine levels decreased by 43% in study I
      and by 28% in study II. In both studies, treatment with B vitamins had no effect
      at all on ADMA, arginine/ADMA ratio and SDMA levels. This result was confirmed in
      multiple linear regression analyses with adjustment for baseline values and
      gender. CONCLUSIONS: Our studies indicate that B vitamins, despite causing a
      substantial reduction in plasma homocysteine levels, have no beneficial effect on
      ADMA levels.

PMID- 16649967
TI  - Peripartum maternal and foetal ghrelin, growth hormones, IGFs and insulin
      interrelations.
AB  - OBJECTIVE: Ghrelin may influence GH secretion and is associated with insulin
      sensitivity. In pregnancy, placental growth hormone (PGH) replaces GH. The aim of
      this study was to investigate the relationship between PGH and ghrelin and their
      relationship to insulin sensitivity in pregnancy. DESIGN: Prospective,
      descriptive study. PATIENTS: Thirty-seven singleton pregnant and six twin
      pregnant women MEASUREMENTS: Maternal blood samples were drawn before and 2 days
      after elective caesarian section (CS). Serum total ghrelin, PGH, GH, GH-binding
      protein, insulin and IGF-I and IGF-II, and plasma glucose were determined.
      Insulin sensitivity indices (ISIs) were calculated. Cord blood samples were drawn
      at delivery for ghrelin determination. RESULTS: Serum ghrelin only displayed a
      minimal, although statistically significant, decrease after CS. Prior to delivery
      serum PGH increased by 25% during fasting, and was undetectable the day after CS.
      Serum levels of GH were low until 48 h after CS. No significant correlations were
      detected between PGH or ghrelin and ISIs, although a trend was observed for
      ghrelin. Twin pregnancies had higher PGH levels than singletons; however, levels
      of IGFs were similar. In cord blood, ghrelin levels were higher in arterial than
      venous samples. CONCLUSIONS: Maternal ghrelin levels were only minimally affected
      by parturition, suggesting that maternal ghrelin is not involved in the
      transition from PGH to GH secretion. The increased arterial ghrelin levels in the
      foetus suggest foetal ghrelin production. Serum PGH appears to be influenced by
      fasting. Finally, elevated PGH levels in twin pregnancies do not appear to affect
      maternal IGF levels.

PMID- 16649968
TI  - Treatment with the aromatase inhibitor letrozole during adolescence increases
      near-final height in boys with constitutional delay of puberty.
AB  - OBJECTIVE: We investigated whether inhibition of oestrogen biosynthesis with the
      aromatase inhibitor, letrozole, during adolescence improves near-final height in
      boys with constitutional delay of puberty. PATIENTS AND METHODS: Seventeen boys
      with constitutional delay of puberty were randomized to receive testosterone (T)
      enanthate (1 mg/kg i.m.) every 4 weeks for 6 months in combination with placebo
      (Pl, n = 8), or the aromatase inhibitor letrozole (Lz, 2.5 mg/day orally) (n =
      9), for 12 months. After treatment, patients were followed up until near-final
      height. Height discrepancy was calculated as near-final height minus mid-parental
      target height. MEASUREMENTS: The primary end point was the difference in near
      final height between the groups treated either with T + Pl or T + Lz.
      Secondarily, height discrepancy and gain in height standard deviation score (SDS)
      were analysed in both groups. RESULTS: Boys treated with T + Lz reached a higher
      mean near-final height than did boys on T + Pl (175.8 vs. 169.1 cm, respectively,
      P = 0.04). In T + Lz-treated boys, mean near-final height did not differ from
      their mid-parental target height (175.8 vs. 177.1 cm, P = 0.38), whereas in T +
      Pl-treated boys, mean near-final height was lower than mid-parental target height
      (169.1 vs. 173.9 cm, P = 0.007). T + Lz-treated boys had a greater increment in
      height SDS over the pretreatment height SDS than T + Pl-treated boys (+1.4 SDS
      vs.+0.8 SDS, P = 0.03). CONCLUSIONS: Our findings indicate that in adolescent
      boys an increase in adult height can be attained by use of aromatase inhibitors.

PMID- 16649969
TI  - Congenital primary hypothyroidism with subsequent adenomatous goiter in a Turkish
      patient caused by a homozygous 10-bp deletion in the thyroid peroxidase (TPO)
      gene.
AB  - OBJECTIVE: Congenital primary hypothyroidism occurs in 1 of 4000 births. Whereas
      the majority of the cases are due to developmental defects of the thyroid gland,
      20% carry a defect in thyroid hormonogenesis. We report a Turkish boy who had
      goitrous hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene.
      DESIGN: The TPO gene was sequenced directly from genomic DNA and cDNA which was
      transcribed from three RNA samples harvested from different parts of the
      patient's excised thyroid gland. Patient The boy was thyroidectomized because of
      continuing growth of his thyroid gland and development of multiple nodes
      suspected of malignancy by ultrasound examination. Histopathological examination
      verified a dyshormonogenetic goiter with multiple follicular adenomas. RESULTS:
      The patient had a novel homozygous 10-bp deletion of the TPO gene at position
      2812 in exon 16. This frame shift mutation results in a severely altered
      intracellular part of the protein. The deletion identified in leucocyte DNA was
      also found in thyroid tissue cDNA - so that instability of the transcript or a
      splicing defect was excluded. Both unaffected parents were heterozygous carriers
      of the mutation whereas 50 healthy individuals of the same ethnic background did
      not harbour the mutation. CONCLUSIONS: The identified TPO gene deletion is the
      first mutation coding for an inactive TPO molecule, which has a severely altered
      intracellular segment. Because the most likely reason for the enlarging goiter
      was poor compliance of the patient, this report underlines the importance of a
      careful and regular follow-up of patients with dyshormonogenesis.

PMID- 16649970
TI  - The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in
      patients with Nelson's syndrome.
AB  - BACKGROUND: Peroxisomal proliferator-activated receptors (PPAR)- gamma are
      expressed abundantly in ACTH-secreting pituitary tumours. The PPAR-gamma
      activator rosiglitazone has been shown to suppress ACTH secretion in human
      adrenocorticotroph tumour cells in vitro, and prevent and reduce
      adrenocorticotroph tumour development in mouse models in vivo. OBJECTIVE: To
      evaluate the effect of rosiglitazone in patients with persistently elevated
      plasma ACTH levels postbilateral adrenalectomy for Cushing's disease. PATIENTS:
      Seven patients were treated with rosiglitazone 8 mg orally per day for 12 weeks.
      MEASUREMENTS: Plasma ACTH was measured at two hourly intervals from 09:00 h to
      17:00 h before and after 6 and 12 weeks of treatment. RESULTS: Plasma ACTH at
      09:00 hours immediately before the usual morning hydrocortisone dose was 2599.0
      +/- 899.7 ng/l (mean +/- SEM) basally and 1547.6 +/- 515.7 ng/l after 12 weeks of
      rosiglitazone, whereas levels at 17:00 h were 1433.4 +/- 506.2 ng/l (mean +/-
      SEM) basally and 1122.3 +/- 460.9 ng/l at 12 weeks (all nonsignificant).
      CONCLUSION: This study showed no effect of rosiglitazone treatment at maximum
      approved doses in lowering plasma ACTH levels in patients post bilateral
      adrenalectomy for Cushing's disease.

PMID- 16649971
TI  - The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese
      Black Americans.
AB  - CONTEXT: Both obesity (body mass index, BMI > or = 30 kg/m2) and Black race are
      associated with a higher risk of vitamin D deficiency and secondary
      hyperparathyroidism. We hypothesized the risk of hypovitaminosis D would
      therefore be extraordinarily high in obese Black adults. OBJECTIVE: To study the
      effects of race and adiposity on 25-hydroxyvitamin D [25(OH)D] and parathyroid
      hormone (iPTH). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 379
      Black and White adults from the Washington D.C. area. BMI ranged from 19.9 to
      58.2 kg/m2. MAIN OUTCOME MEASURES: Prevalence of hypovitaminosis D [25(OH)D <
      37.5 nmol/l] and secondary hyperparathyroidism [25(OH)D < 37.5 nmol/l with iPTH >
      4.2 pmol/l]. RESULTS: Obese Black subjects had lower mean 25(OH)D, 40.3 (SD,
      20.3) nmol/l, compared with obese Whites, 64.5 (29.7), P < 0.001, nonobese
      Blacks, 53.3 (26.0), P = 0.0025 and nonobese Whites, 78.0 (33.5), P < 0.001. The
      prevalence of hypovitaminosis D increased with increasing BMI, and was greater (P
      < 0.001) in Blacks than Whites within all BMI categories examined. Among subjects
      with BMI > or = 35 kg/m2, 59% of Blacks vs 18% of Whites had hypovitaminosis D
      (odds ratio 6.5, 95% confidence interval 3.0-14.2). iPTH was negatively
      correlated with 25(OH)D (r = -0.31, P < 0.0001), suggesting those with
      hypovitaminosis D had clinically important vitamin D deficiency with secondary
      hyperparathyroidism. For secondary hyperparathyroidism 35.2% of Blacks met the
      criteria, compared to 9.7% of Whites (OR 3.6, CI 1.5-98.8). CONCLUSIONS: Obese
      Black Americans are at particularly high risk for vitamin D deficiency and
      secondary hyperparathyroidism. Physicians should consider routinely supplementing
      such patients with vitamin D or screening them for hypovitaminosis D.

PMID- 16649972
TI  - Differences in cortisol concentrations in South Asian and European men living in
      the United Kingdom.
AB  - OBJECTIVE: The metabolic syndrome is more prevalent in South Asians in Britain
      than in the general population. Furthering our understanding of the underlying
      mechanisms is important because of the increased risk of cardiovascular disease
      associated with the metabolic syndrome. As it has been proposed that increased
      activity of the hypothalamic pituitary adrenal axis might underlie the metabolic
      syndrome, we hypothesized that plasma cortisol levels would be higher in South
      Asians and that increased cortisol levels would be associated with cardiovascular
      risk factors comprising the metabolic syndrome. The aim of the study was to
      examine ethnic differences in cortisol levels and to compare the relationships
      between cortisol levels and cardiovascular risk factors in men from different
      ethnic groups. DESIGN: Cross-sectional population-based study, Newcastle upon
      Tyne, UK. (Newcastle Heart project). Participants One hundred men, 40-67 years
      old, of European and South Asian (Indian, Pakistani, Bangladeshi) ancestry, with
      and without cardiovascular risk factors of the metabolic syndrome. MEASUREMENTS:
      Measurement of plasma cortisol and corticosteroid binding globulin in stored
      sera. RESULTS: After adjustment for age and the presence of cardiovascular risk
      factors, mean cortisol was 27% (95% CI, 10%, 40%) lower in South Asians compared
      to Europeans. Cortisol levels were higher in all men with cardiovascular risk
      factors than those without. CONCLUSIONS: Cortisol levels are lower in South Asian
      than in European men resident in the UK. Despite lower cortisol levels in South
      Asians, the relations between cortisol and cardiovascular risk factors remain
      strong.

PMID- 16649973
TI  - The effect of abdominal obesity on insulin sensitivity and serum lipid and
      cytokine concentrations in African women.
AB  - OBJECTIVES: Studies have shown clear associations of abdominal obesity with lipid
      and glucose metabolism and cytokine levels in a number of different population
      groups. However, no such studies have been performed in an African population in
      which visceral adipose tissue levels have been shown to be lower than in European
      subjects. DESIGN AND PATIENTS: Cross-sectional analysis in 124 African women.
      MEASUREMENTS: Fasting serum samples were taken from all subjects and
      anthropometric measurements obtained. Blood levels of glucose, insulin, total
      cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured.
      Subjects were separated into normal and abnormal glucose tolerant groups and into
      tertiles according to waist circumference (WC). Insulin resistance was assessed
      using the homeostasis model assessment (HOMA). RESULTS: Abnormal glucose-tolerant
      subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant
      group. Increased WC was associated with higher triglyceride, insulin and HOMA
      levels and lower HDL levels. Multiple regression analyses showed that WC
      associated positively with HOMA and serum triglyceride levels and negatively with
      HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI
      correlated positively with serum IL-6 concentrations. CONCLUSIONS: Although
      previous studies have shown that African subjects have a lower visceral adipose
      depot size than European subjects, abdominal obesity is still associated with
      insulin resistance and dyslipidaemia. The association between abdominal obesity
      and metabolic dysfunction within this population is not dependent upon IL-6, IL-8
      or IL-18.

PMID- 16649974
TI  - Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting
      pituitary adenomas.
AB  - OBJECTIVE: To assess the medium-term outcome in a cohort of patients with
      residual or recurrent pituitary adenoma treated with fractionated stereotactic
      conformal radiotherapy (SCRT). PATIENTS AND METHODS: Ninety-two patients (median
      age 50 years) with a residual or recurrent nonfunctioning (67) or a secreting
      (25) pituitary adenoma were treated between 1995 and 2003. Eighteen patients had
      a GH-secreting, five PRL-secreting and two an ACTH-secreting pituitary adenoma.
      Vision was impaired in 39 patients, with visual field deficit (35) and/or reduced
      visual acuity (25). Sixty-four patients had partial or complete hypopituitarism
      before SCRT. The treatment was delivered stereotactically by four noncoplanar
      conformal fixed fields using a 6-MV linear accelerator to a dose of 45 Gy in 25
      fractions. RESULTS: At a median follow-up of 32 months (range 4-108) the 1, 3 and
      5 years actuarial progression-free survival is 99%, 98% and 98%, and overall
      survival is 98%. Three patients recurred 5 months, 1 year and 9 years after SCRT
      requiring surgery. In secreting adenomas, hormone levels declined progressively,
      becoming normal in more than a third of patients with GH-secreting and PRL
      secreting pituitary tumours. 50% of baseline GH level was achieved in just under
      2 years. The treatment was well tolerated with minimal acute toxicity.
      Hypopituitarism was the most common long-term effect; 22% of patients had
      worsening of pituitary function. One patient developed unilateral quadrantopia
      without tumour progression. CONCLUSION: SCRT as a high-precision technique of
      localized irradiation achieves tumour and hormone control of pituitary adenomas
      comparable with previously published data on the efficacy of conventional
      radiotherapy. Despite the potential advantage of reducing the volume of normal
      brain irradiated, the theoretical benefit over conventional radiotherapy in terms
      of the reduction in long-term morbidity has not yet been demonstrated and
      requires longer follow-up. Potential effect on long-term cognitive function has
      not been tested.

PMID- 16649975
TI  - Persisting effects on fasting glucose levels and insulin sensitivity after 6
      months of discontinuation of a very low-dose GH therapy in adults with severe GH
      deficiency.
AB  - OBJECTIVE: We recently reported that, in contrast to the standard GH (SGH)
      replacement dose titrated to normalize serum IGF-I levels, 12-month treatment
      with a fixed low GH dose (LGH) (0.1 mg/day) decreased fasting glucose levels and
      improved insulin sensitivity with little effect on body composition in severely
      GH-deficient adults. In this study, we have subsequently examined the effects
      after 6 months of discontinuation of these variable GH doses (LGH: n = 8; fixed
      dose 0.10 mg/day and SGH: n = 8; mean dose 0.50 mg/day) on glucose metabolism,
      body composition and other surrogate cardiovascular risk markers. METHODS:
      Fasting insulin sensitivity using the homeostasis model assessment, and body
      composition using dual-energy X-ray absorptiometry scans were assessed at
      baseline, after 12 months of therapy (month 12) and after 6 months following
      discontinuation of therapy (month 18). RESULTS: At month 12, the LGH decreased
      fasting glucose levels and improved insulin sensitivity without altering body
      composition, whereas the SGH improved body composition without modifying insulin
      sensitivity. Six months after discontinuation of the LGH treatment (month 18),
      fasting glucose levels remained decreased and the enhanced insulin sensitivity
      persisted. In contrast, after discontinuation of SGH treatment (month 18), body
      composition reverted to baseline without changes in either fasting glucose levels
      or insulin sensitivity. CONCLUSION In contrast to the SGH, the LGH induces
      effects on fasting glucose levels and insulin sensitivity, which persist after 6
      months of discontinuation of therapy. The exact molecular mechanisms are unclear
      but may involve the modulation of hepatic and muscle insulin sensitivity,
      possibly by altering insulin and IGF-I receptor responsiveness and/or density.

PMID- 16649976
TI  - GH replacement does not increase the risk of recurrence in patients with
      craniopharyngioma.
AB  - BACKGROUND: A significant number of patients with craniopharyngioma are GH
      deficient. The safety of GH replacement in these subjects has not been
      established. OBJECTIVE: To assess the effect of GH replacement upon recurrence in
      patients with craniopharyngioma. PATIENTS AND METHODS: All the patients with
      craniopharyngioma followed-up at the Departments of Endocrinology or Paediatrics
      in Oxford and treated or not with GH were studied retrospectively. These were
      recruited from the databases of the departments consisting of subjects diagnosed
      between January 1964 and July 2005. The impact of GH replacement upon recurrence
      was evaluated after adjusting for possible confounding factors. RESULTS: Forty
      one subjects received GH replacement. Nine of them did not have follow-up imaging
      during GH therapy and were not included in the statistical analyses. The
      remaining 32 (22 males/10 females) received GH for a mean period of 6.3 +/- 4.6
      years (median 5.1, range 0.8-22); 21 started during childhood (13 of them
      continued after the achievement of final height with an adult dose) and 11 during
      adult life. The mean duration of their follow-up (from surgery until last
      assessment) was 10.8 +/- 9.2 years (range 1.9-40). Fifty-three subjects had not
      received GH therapy (30 men/23 women). The mean duration of their follow-up (from
      surgery until last assessment) was 8.3 +/- 8.8 years (range 0.5-36). During the
      observation period, 4 patients treated with GH and 22 non-GH treated ones
      developed tumour recurrence. After adjusting for sex, age at tumour diagnosis and
      type of tumour therapy (gross total removal, partial removal, surgery +
      irradiation), GH treatment was not a significant independent predictor of
      recurrence (P = 0.06; hazard ratio = 0.309). Similar results were obtained when
      the impact of GH replacement was assessed according to its duration (P = 0.18;
      hazard ratio = 0.991/month of treatment). None of the nine patients with
      insufficient imaging data for inclusion in the statistical analyses [5 men/4
      women, 3 treated with GH during childhood/6 during adult life, mean duration of
      GH therapy 2.9 +/- 2.4 years (median 1.8, range 0.4-7)] showed clinical features
      suggestive of recurrence during the period of GH replacement. CONCLUSION Based on
      the data of the craniopharyngiomas database in Oxford, there is no evidence that
      GH replacement is associated with an increased risk of tumour recurrence.

PMID- 16649977
TI  - A rare RET gene exon 8 mutation is found in two Greek kindreds with familial
      medullary thyroid carcinoma: implications for screening.
AB  - OBJECTIVE: Familial medullary thyroid carcinoma (FMTC) is caused by germ-line
      mutations in the RET proto-oncogene. These mutations concern mainly cysteine
      residues in exons 10 and 11, whereas noncysteine mutations in exons 13-16 are
      rare. Mutations in other exons have been reported only in isolated families. In
      this study we have analysed the RET gene in two FMTC families negative for
      mutations in the above exons. DESIGN: We have analysed exons 7-19 and 21 in one
      index patient from each family using DNA sequencing. PATIENTS: Twenty-eight
      subjects from both families were clinically assessed and subsequently molecularly
      analysed for the presence of RET gene mutations. RESULTS: We have found the
      mutation c.1597G-->T (Gly533Cys) in two Greek families with FMTC. The mutation
      was detected in all seven MTC patients of both families as well as in 13
      asymptomatic relatives in the heterozygote state, although one of the patients
      was also a homozygote due to consanguinity. The mutation shows a wide clinical
      heterogeneity, as there are carrier patients with age of diagnosis ranging from
      23 to 88 years. CONCLUSIONS: It is likely that this mutation causes FMTC, as no
      other mutation was found in the RET gene, the mutation co-segregates with FMTC,
      and family members without the mutation are clinically unaffected. As the same
      point mutation was previously found in a large Brazilian family, it may be
      present in other populations as well. Therefore, exon 8 of RET should be screened
      in FMTC families with no identified common RET mutations.

PMID- 16649978
TI  - The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia.
AB  - OBJECTIVE: There is controversy about the effects of statins on insulin
      resistance and plasma adiponectin. The aim of this study was to investigate the
      effects of fluvastatin treatment on these parameters in a group of dyslipidaemic
      patients who had no confounding factors for insulin resistance or alterations in
      plasma adiponectin. DESIGN AND PATIENTS: Forty-nine patients [27 males, 22
      females; mean age 47.2 +/- 10.3 years; body mass index (BMI) 29.64 +/- 3.2 kg/m2]
      with dyslipidaemia and 20 controls (six males, 14 females; mean age 45.3 +/- 9.31
      years; BMI 30.07 +/- 4.04 kg/m2) were enrolled. All patients were treated
      initially with therapeutic lifestyle changes (TLC) for 6 weeks. Six out of 49
      subjects were excluded from the study. Then, 24 out of 43 patients with high
      blood cholesterol despite TLC were allocated to fluvastatin 80 mg daily plus TLC,
      and the remaining 19 patients with normal cholesterol were subjected to TLC alone
      for additional 12 weeks. MEASUREMENTS: Plasma adiponectin, immunoreactive insulin
      levels, BMI, waist circumference, blood pressure, lipids, and glucose were
      determined. The insulin sensitivity index was quantified using the homeostasis
      model assessment (HOMA). RESULTS: TLC caused significant improvement in plasma
      insulin (P = 0.02) and elevation in plasma adiponectin (P = 0.02). Fluvastatin
      treatment decreased total cholesterol and low density lipoprotein (LDL)
      cholesterol significantly (P = 0.01 and P = 0.02, respectively). No significant
      effect of fluvastatin was observed on plasma insulin or adiponectin or on the
      HOMA index. CONCLUSIONS: Fluvastatin does not improve plasma adiponectin levels
      and insulin sensitivity, despite its beneficial effects on lipid levels. Our
      data, however, were limited by the fact that a more accurate method of assessing
      insulin sensitivity, the euglycaemic-hyperinsulinaemic glucose clamp technique,
      was not used.

PMID- 16649979
TI  - Immunogenetic association and thyroid autoantibodies in juvenile autoimmune
      thyroiditis in North India.
AB  - OBJECTIVES: Autoimmune thyroid diseases (AITD) encompass a number of conditions
      that have in common cellular and humoral responses targeting the thyroid gland.
      Interactions between susceptibility genes and environmental triggers are thought
      to initiate an autoimmune response to thyroid antigens leading to disease
      manifestation. Commencement of the disease in childhood leads to the presumption
      that genetics may have an important role in the causation of the disease. DESIGN:
      The present study was aimed at evaluating the human leucocyte antigen (HLA)
      encoded susceptibility to develop juvenile autoimmune thyroiditis (JAT) in
      patients from North India. PATIENTS: We studied 48 consecutive patients of JAT
      along with 176 first-degree relatives for their thyroid function (FT4, TSH) and
      anti-thyroid peroxidase antibody status (AbTPO). MEASUREMENTS: HLA studies were
      carried out using serology for HLA-class I antigens and DNA analysis of HLA-class
      II alleles. The data were compared with a cohort of 308 ethnically matched
      healthy individuals. RESULTS: We observed overt hypothyroidism in 50% and AbTPO
      positivity in 70.8% of the index cases. Among the first-degree relatives, goitre
      was observed in 51.7%, thyroid dysfunction in 28.4% and AbTPO in 29.5% of
      individuals. Of the 37 relatives who underwent fine-needle aspiration cytology
      (FNAC), 60% had evidence of chronic lymphocytic thyroiditis (CLT). A strong
      positive association of HLA-DRB1*1404 was observed with the JAT (35.4%vs. 10.4%,
      chi2 = 19.8, Pc = 0.0001). We also observed a higher (72%, P = 0.03) paternal
      transmission of HLA-DRB1*1404 to affected offspring in comparison to unaffected
      offspring. HLA-DRB1*03 was also increased among JAT patients but did not reach
      statistical significance. CONCLUSION: These studies point towards an important
      role of immune modifying genes, such as HLA, in influencing susceptibility to
      juvenile-onset AITD.

PMID- 16649980
TI  - Novel mutations in the calcium-sensing receptor gene associated with biochemical
      and functional differences in familial hypocalciuric hypercalcaemia.
AB  - OBJECTIVE: Heterozygous inactivating mutations of the calcium-sensing receptor
      (CaR) gene cause familial hypocalciuric hypercalcaemia (FHH), a generally benign
      disorder characterized by mild to moderate PTH-dependent hypercalcaemia. We aimed
      to identify the causative CaR mutations in three families with FHH and examine
      the correlation between type of mutation and biochemical and/or functional
      phenotypes. PATIENTS, DESIGN AND MEASUREMENTS: The CaR gene from FHH family
      members was assessed for mutations by direct DNA sequencing and mutations were
      confirmed by restriction enzyme analysis. Functional studies on two missense
      mutations were conducted by introducing them by site-directed mutagenesis into
      the CaR cloned into a mammalian expression vector, and assessing calcium
      responsiveness using an inositol phosphate (IP) assay in HEK293 cells.
      Biochemical data from patients heterozygous for each type of mutant were
      correlated with functionality. RESULTS: Two novel nonsense mutations (R25stop and
      K323stop) and one novel missense mutation (G778D) were identified. The G778D
      mutant receptor and another mutation identified in an earlier study (L174R)
      demonstrated a complete lack of Ca2+ responsiveness using the IP assay. When
      cotransfected with wild-type receptor, the mutant receptors demonstrated a
      dominant-negative effect on wild-type receptor response, with L174R having a more
      pronounced effect than G778D. Significantly more severe hypercalcaemia and a
      trend towards higher PTH levels were observed in patients heterozygous for CaR
      mutants with a stronger dominant-negative effect. CONCLUSIONS: Naturally
      occurring CaR mutations with differences in dominant-negative effect on wild-type
      receptor demonstrate differences in biochemical severity in FHH.

PMID- 16649981
TI  - Gamma knife radiosurgery for acromegaly--long-term experience.
AB  - OBJECTIVE: The Leksell gamma knife (LGK) is one of the treatment options for
      pituitary adenomas. We report on our long-term experience treating acromegaly
      using LGK. DESIGN: Since 1993 we have followed 96 acromegaly patients through
      periods of from 12 to 120 months. The mean follow-up period was 53.7 +/- 26.8
      months. Seventy-two patients were treated with neurosurgery prior to LGK; for 24
      LGK was the primary treatment. Thirteen patients were irradiated twice, due to
      persistent activity of the adenoma or its residue. Pituitary functions were
      tested at 6-month intervals, post-irradiation. The target tumour volume for
      radiosurgery was between 93.3 and 12 700 mm3 (median 1350 mm3). RESULTS: Fifty
      per cent of the patients achieved mean GH < 2.5 microg/l within 42 months,
      normalized their IGF-I within 54 months, and achieved GH suppression in the oral
      glucose tolerance test (oGTT) < 1 microg/l with normal IGF-I within 66 months.
      LGK effectiveness was dependent on initial adenoma hormonal activity (GH and IGF
      I serum levels), not on the size of the adenoma. Patients with primary
      neurosurgery followed by LGK irradiation had better outcomes than those with LGK
      alone. Irradiation arrested all adenoma growth, causing tumour shrinkage in 62.3%
      of patients. Twenty-six developed hypopituitarism when irradiated by 15 Gy (or
      more) on functional peritumoral pituitary tissue. No hypopituitarism appeared
      using lower doses. CONCLUSIONS: In acromegaly, LGK is a useful adjunct to primary
      neurosurgery when treating post-surgical residues because it can limit the
      duration of medical therapy. It can be used as a primary therapy when
      neurosurgery is not possible.

PMID- 16649982
TI  - IGF-secreting tumour treated with a combination of growth hormone and
      glucocorticoids.

PMID- 16649983
TI  - Leptin levels in breast-fed infants.

PMID- 16649984
TI  - The effect of newly diagnosed hypothyroidism on serum sodium concentrations: a
      retrospective study.

PMID- 16649985
TI  - Maternal hypothyroidism in early gestation: possible preventive strategies.

PMID- 16649987
TI  - The mitochondrial permeability transition from in vitro artifact to disease
      target.
AB  - The mitochondrial permeability transition pore is a high conductance channel
      whose opening leads to an increase of mitochondrial inner membrane permeability
      to solutes with molecular masses up to approximately 1500 Da. In this review we
      trace the rise of the permeability transition pore from the status of in vitro
      artifact to that of effector mechanism of cell death. We then cover recent
      results based on genetic inactivation of putative permeability transition pore
      components, and discuss their meaning for our understanding of pore structure.
      Finally, we discuss evidence indicating that the permeability transition pore
      plays a role in pathophysiology, with specific emphasis on in vivo models of
      disease.

PMID- 16649988
TI  - RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3beta.
AB  - The RCAN1 protein (previously called calcipressin 1 or MCIP1) binds to
      calcineurin, a serine/threonine phosphatase (PP2B), and inhibits its activity.
      Here we demonstrate that regulated overexpression of an RCAN1 transgene (this
      gene was previously called DSCR1 or Adapt78) also stimulates expression of the
      GSK-3beta kinase, which can antagonize the action of calcineurin. We also show
      that GSK-3beta is regulated by RCAN1 at a post-transcriptional level. In humans,
      high RCAN1 expression is found in the brain, where at least two mRNA isoforms
      have been reported. Therefore, we further investigated expression of the various
      RCAN1 isoforms, resulting from differential splicing and alternative promotors in
      human brain. We detected at least three distinct RCAN1s: RCAN1-1 Short at 31 kDa
      (RCAN1-1S), RCAN1-1 Long at 38 kDa (RCAN1-1 L), and RCAN1-4. Furthermore, the
      levels of RCAN1-1S, but not RCAN1-1 L or RCAN1-4 correlated with the levels of
      GSK-3beta. This suggests that RCAN1-1S might induce production of GSK-3beta in
      vivo. While RCAN1s can regulate calcineurin and GSK-3beta, it has also been shown
      that calcineurin and GSK-3beta can regulate RCAN1s. Here we propose a new model
      (incorporating all these findings) in which cells maintain an equilibrium between
      RCAN1s, calcineurin, and GSK-3beta.

PMID- 16649989
TI  - Regulated cleavage of intracellular glycosylphosphatidylinositol in a
      trypanosome. Peroxisome-to-endoplasmic reticulum translocation of a phospholipase
      C.
AB  - Cell exposure to hypo-osmolarity and alkalinity triggers a spectrum of responses
      including activation of phospholipases. Glycosylphosphatidylinositol-specific
      phospholipase C (GPI-PLC) is expressed in Trypanosoma brucei, a protozoan
      parasite that causes human African trypanosomiasis. We examined possible
      contributions of GPI-PLC to the response of T. brucei to hypo-osmotic or mildly
      alkaline conditions. GPIs were detected at the endoplasmic reticulum (ER). They
      were cleaved after exposure of T. brucei to hypo-osmolarity or mild alkalinity,
      which also, strikingly, caused translocation of GPI-PLC from glycosomes
      (peroxisomes) to the ER. A catalytically inactive Gln81Leu mutant of GPI-PLC
      failed to cleave GPIs despite being transported from glycosomes to the ER after
      hypo-osmotic or mild alkaline treatment of the parasites. In contrast, a
      Cys347Ser mutant of the enzyme could not exit glycosomes after treatment of cells
      expressing the protein with mild base or hypo-osmotic buffer. We conclude that:
      (a) GPI-PLC contributes to loss of GPIs in T. brucei treated with hypo-osmotic or
      mildly alkaline buffer; (b) access of GPI-PLC to its substrate in vivo can be
      regulated post-translationally; (c) translocation of GPI-PLC from glycosomes to
      the ER is important for in vivo cleavage of GPIs; (d) Cys347 is part of a peptide
      motif required for post-translational targeting of GPI-PLC to the ER. Glycosome
      to-ER movement of GPI-PLC reveals a novel pathway for intracellular protein
      traffic. The physiological significance of GPI digestion in cells exposed to
      mildly alkalinity or hypo-osmolarity is discussed.

PMID- 16649990
TI  - The guanine nucleotide exchange factor RasGRF1 directly binds microtubules via
      DHPH2-mediated interaction.
AB  - RasGRF is a family of guanine nucleotide exchange factors with dual specificity
      for both Ras and Rac GTPases. In this study, using mouse brain extracts, we show
      that both RasGRF1 and RasGRF2 interact with microtubules in an in vitro
      microtubule assembly system and this binding is very tight. To characterize this
      association, recombinant purified proteins containing different regions of
      RasGRF1 were tested for their ability to bind microtubules preassembled from pure
      tubulin. Only the DHPH2 tandem directly associates with microtubules, whereas the
      isolated DH or PH2 domains do not, indicating that the entire DHPH2 region is
      required for this association. The interaction occurs with high affinity (Kd
      approximately = 2 microM) and with a stoichiometry, at saturating conditions, of
      one DHPH2 molecule for two tubulin dimers. Competition experiments support the
      hypothesis that the DHPH2 module is largely responsible for RasGRF1-microtubule
      interaction. In vivo colocalization of RasGRF1 and microtubules was also observed
      by fluorescence confocal microscopy in nonneuronal cells after stimulation with
      an oxidative stress agent and in highly differentiated neuron-like cells.
      Identification of microtubules as new binding partners of RasGRF1 may help to
      elucidate the signaling network in which RasGRF1 is involved.

PMID- 16649991
TI  - The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly
      dynamics through tubulin binding. A possible mechanism for its antiproliferative
      activity.
AB  - Sanguinarine has been shown to inhibit proliferation of several types of human
      cancer cell including multidrug-resistant cells, whereas it has minimal
      cytotoxicity against normal cells such as neutrophils and keratinocytes. By
      analyzing the antiproliferative activity of sanguinarine in relation to its
      effects on mitosis and microtubule assembly, we found that it inhibits cancer
      cell proliferation by a novel mechanism. It inhibited HeLa cell proliferation
      with a half-maximal inhibitory concentration of 1.6 +/- 0.1 microM. In its lower
      effective inhibitory concentration range, sanguinarine depolymerized microtubules
      of both interphase and mitotic cells and perturbed chromosome organization in
      mitotic HeLa cells. At concentrations of 2 microM, it induced bundling of
      interphase microtubules and formation of granular tubulin aggregates. A brief
      exposure of HeLa cells to sanguinarine caused irreversible depolymerization of
      the microtubules, inhibited cell proliferation, and induced cell death. However,
      in contrast with several other microtubule-depolymerizing agents, sanguinarine
      did not arrest cell cycle progression at mitosis. In vitro, low concentrations of
      sanguinarine inhibited microtubule assembly. At higher concentrations (> 40
      microM), it altered polymer morphology. Further, it induced aggregation of
      tubulin in the presence of microtubule-associated proteins. The binding of
      sanguinarine to tubulin induces conformational changes in tubulin. Together, the
      results suggest that sanguinarine inhibits cell proliferation at least in part by
      perturbing microtubule assembly dynamics.

PMID- 16649992
TI  - Crustacean hyperglycemic and vitellogenesis-inhibiting hormones in the lobster
      Homarus gammarus.
AB  - Crustacean hyperglycemic hormone (CHH) and vitellogenesis-inhibiting hormone
      (VIH), produced by the X organ-sinus gland neurosecretory complex, belong to a
      peptide group referred to as the CHH family, which is widely distributed in
      arthropods. In this study, genetic variants and post-translationally modified
      isoforms of CHH and VIH were characterized in the European lobster Homarus
      gammarus. With the use of RP-HPLC and ELISA with specific antibodies that
      discriminate between stereoisomers of CHH and VIH, two groups of CHH
      immunoreactive peaks were characterized from HPLC fractions of sinus gland
      extract (CHH A and CHH B); each group contained two variants (CHH and D-Phe3CHH).
      In the same way, two VIH-immunoreactive peaks (VIH and D-Trp4VIH) were
      demonstrated in HPLC fractions from sinus gland extract. The masses of these
      different neuropeptides were determined by FT-ICR MS: CHH A and CHH B spectra
      exhibited monoisotopic ions at 8557.05 Da and 8527.04 Da, respectively, and both
      VIH isomers displayed an m/z value of 9129.19 Da. Two full-length cDNAs encoding
      preprohomones of CHH A and CHH B and only one cDNA for VIH precursor were cloned
      and sequenced from X organ RNA. Comparison of CHH sequences between European
      lobster and other Astacoidea suggests that the most hydrophobic form appeared
      first during crustacean evolution.

PMID- 16649993
TI  - Structure of the complex of a yeast glucoamylase with acarbose reveals the
      presence of a raw starch binding site on the catalytic domain.
AB  - Most glucoamylases (alpha-1,4-D-glucan glucohydrolase, EC 3.2.1.3) have
      structures consisting of both a catalytic and a starch binding domain. The
      structure of a glucoamylase from Saccharomycopsis fibuligera HUT 7212 (Glu),
      determined a few years ago, consists of a single catalytic domain. The structure
      of this enzyme with the resolution extended to 1.1 A and that of the enzyme
      acarbose complex at 1.6 A resolution are presented here. The structure at atomic
      resolution, besides its high accuracy, shows clearly the influence of cryo
      cooling, which is manifested in shrinkage of the molecule and lowering the volume
      of the unit cell. In the structure of the complex, two acarbose molecules are
      bound, one at the active site and the second at a site remote from the active
      site, curved around Tyr464 which resembles the inhibitor molecule in the 'sugar
      tongs' surface binding site in the structure of barley alpha-amylase isozyme 1
      complexed with a thiomalto-oligosaccharide. Based on the close similarity in
      sequence of glucoamylase Glu, which does not degrade raw starch, to that of
      glucoamylase (Glm) from S. fibuligera IFO 0111, a raw starch-degrading enzyme, it
      is reasonable to expect the presence of the remote starch binding site at
      structurally equivalent positions in both enzymes. We propose the role of this
      site is to fix the enzyme onto the surface of a starch granule while the active
      site degrades the polysaccharide. This hypothesis is verified here by the
      preparation of mutants of glucoamylases Glu and Glm.

PMID- 16649994
TI  - Modulation of glucocorticoid receptor-interacting protein 1 (GRIP1)
      transactivation and co-activation activities through its C-terminal repression
      and self-association domains.
AB  - Glucocorticoid receptor-interacting protein 1 (GRIP1), a p160 family nuclear
      receptor co-activator, possesses at least two autonomous activation domains (AD1
      and AD2) in the C-terminal region. AD1 activity appears to be mediated by
      CBP/p300, whereas AD2 activity is apparently mediated through co-activator
      associated arginine methyltransferase 1 (CARM1). The mechanisms responsible for
      regulating the activities of AD1 and AD2 are not well understood. We provide
      evidence that the GRIP1 C-terminal region may be involved in regulating its own
      transactivation and nuclear receptor co-activation activities through primary
      self-association and a repression domain. We also compared the effects of the
      GRIP1 C terminus with those of other factors that functionally interact with the
      GRIP1 C terminus, such as CARM1. Based on our results, we propose a regulatory
      mechanism involving conformational changes to GRIP1 mediated through its
      intramolecular and intermolecular interactions, and through modulation of the
      effects of co-repressors on its repression domains. These are the first results
      to indicate that the structural components of GRIP1, especially those of the C
      terminus, might functionally modulate its putative transactivation activities and
      nuclear receptor co-activator functions.

PMID- 16649995
TI  - The role of interface framework residues in determining antibody V(H)/V(L)
      interaction strength and antigen-binding affinity.
AB  - While many antibodies with strong antigen-binding affinity have stable variable
      regions with a strong antibody heavy chain variable region fragment
      (V(H))/antibody light chain variable region fragment (V(L)) interaction, the anti
      lysozyme IgG HyHEL-10 has a fairly strong affinity, yet a very weak V(H)/V(L)
      interaction strength, in the absence of antigen. To investigate the possible
      relationship between antigen-binding affinity and V(H)/V(L) interaction strength,
      a novel phage display system that can switch two display modes was employed. We
      focused on the two framework region 2 regions of the HyHEL-10 V(H) and V(L),
      facing each other at the domain interface, and a combinatorial library was made
      in which each framework region 2 residue was mixed with that of D1.3, which has a
      far stronger V(H)/V(L) interaction. The phagemid library, encoding V(H) gene 7
      and V(L) amber codon gene 9, was used to transform TG-1 (sup+), and the phages
      displaying functional variable regions were selected. The selected phages were
      then used to infect a nonsuppressing strain, and the culture supernatant
      containing V(H)-displaying phages and soluble V(L) fragment was used to evaluate
      the V(H)/V(L) interaction strength. The results clearly showed the existence of a
      key framework region 2 residue (H39) that strongly affects V(H)/V(L) interaction
      strength, and a marked positive correlation between the antigen-binding affinity
      and the V(H)/V(L) interaction, especially in the presence of a set of particular
      V(L) residues. The effect of the H39 mutation on the wild-type variable region
      was also confirmed by a SPR biosensor as a several-fold increase in antigen
      binding affinity owing to an increased association rate, while a slight decrease
      was observed for the single-chain variable region.

PMID- 16649996
TI  - SHP-1 dephosphorylates 3BP2 and potentially downregulates 3BP2-mediated T cell
      antigen receptor signaling.
AB  - Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1 (SHP-1) is
      a critical inhibitory regulator in T cell-receptor (TCR) signaling. However, the
      exact molecular mechanism underlying this is poorly defined, largely because the
      physiological substrates for SHP-1 in T cells remain elusive. In this study, we
      showed that adaptor protein 3BP2 serves as a binding protein and a physiological
      substrate of SHP-1. 3BP2 is phosphorylated on tyrosyl residue 448 in response to
      TCR activation, and the phosphorylation is required for T cell signalling, as
      indicated by transcriptional activation of nuclear factor activated in T cells
      (NFAT). Concurrently, phosphorylation of Tyr566 at the C-terminus of SHP-1 causes
      specific recruitment of 3BP2 to the phosphatase through the SH2 domain of the
      adaptor protein. This leads to efficient dephosphorylation of 3BP2 and thereby
      termination of T cell signaling. The study thus defines a novel function of the C
      terminal segment of SHP-1 and reveals a new mechanism by which T cell signaling
      is regulated.

PMID- 16649997
TI  - Differing molecular mechanisms appear to underlie early toxicity of prefibrillar
      HypF-N aggregates to different cell types.
AB  - Considerable attention has been paid to the high cytotoxic potential of small,
      prefibrillar aggregates of proteins/peptides, either associated or not associated
      with amyloid diseases. Recently, we reported that different cell types are
      variously affected by early aggregates of the N-terminal domain of the
      prokaryotic hydrogenase maturation factor HypF (HypF-N), a protein not involved
      in any disease. In this study, we provide detailed information on a chain of
      events triggered in Hend murine endothelial cells and IMR90 fibroblasts, which
      have previously been shown to be highly vulnerable or very resistant,
      respectively, to HypF-N aggregates. Initially, both cell lines displayed impaired
      viability upon exposure to HypF-N toxic aggregates; however, at longer exposure
      times, IMR90 cells recovered completely, whereas Hend cells did not. In
      particular, significant initial mitochondrial permeability transition (MPT) pore
      opening was found in IMR90 cells followed by a sudden repair of membrane
      integrity with rapid and efficient inhibition of cytochrome c and AIF release,
      and upregulation of Bcl-2. The greater resistance of IMR90 fibroblasts may also
      be due to a higher cholesterol content in the plasma membrane, which disfavours
      interaction with the aggregates. In contrast, Hend cells, which have less
      membrane cholesterol, showed delayed MPT opening with prolonged translocation of
      cytochrome c into the cytosol. Finally, the caspase 9 active fragment was
      increased significantly in both Hend and IMR90 cells; however, only Hend cells
      showed caspase 8 and caspase 3 activation with DNA fragmentation. From our data,
      the different responses of the two cell types to the same aggregates appear to be
      associated with two key events: (a) aggregate interaction with the plasma
      membrane, disfavoured by a high level of membrane cholesterol; and (b)
      alterations in mitochondrial functionality, leading to the release of pro
      apoptotic stimuli, which are counteracted by upregulation of Bcl-2.

PMID- 16649998
TI  - Kinetic deuterium isotope effects for 7-alkoxycoumarin O-dealkylation reactions
      catalyzed by human cytochromes P450 and in liver microsomes. Rate-limiting C-H
      bond breaking in cytochrome P450 1A2 substrate oxidation.
AB  - 7-Ethoxy (OEt) coumarin has been used as a model substrate in many cytochrome
      P450 (P450) studies, including the use of kinetic isotope effects to probe facets
      of P450 kinetics. P450s 1A2 and 2E1 are known to be the major catalysts of 7-OEt
      coumarin O-deethylation in human liver microsomes. Human P450 1A2 also catalyzed
      3-hydroxylation of 7-methoxy (OMe) coumarin at appreciable rates but P450 2E1 did
      not. Intramolecular kinetic isotope effects were used as estimates of the
      intrinsic kinetic deuterium isotope effects for both 7-OMe and 7-OEt coumarin
      dealkylation reactions. The apparent intrinsic isotope effect for P450 1A2 (9.4
      for O-demethylation, 6.1 for O-deethylation) showed little attenuation in other
      competitive and noncompetitive experiments. With P450 2E1, the intrinsic isotope
      effect (9.6 for O-demethylation, 6.1 for O-deethylation) was attenuated in the
      noncompetitive intermolecular experiments. High noncompetitive intermolecular
      kinetic isotope effects were seen for 7-OEt coumarin O-deethylation in a
      baculovirus-based microsomal system and five samples of human liver microsomes
      (7.3-8.1 for O-deethylation), consistent with the view that P450 1A2 is the most
      efficient P450 catalyzing this reaction in human liver microsomes and indicating
      that the C-H bond-breaking step makes a major contribution to the rate of this
      P450 (1A2) reaction. Thus, the rate-limiting step appears to be the chemistry of
      the breaking of this bond by the activated iron-oxygen complex, as opposed to
      steps involved in the generation of the reactive complex. The conclusion about
      the rate-limiting step applies to all of the systems studied with this model P450
      1A2 reaction including human liver microsomes, the most physiologically relevant.

PMID- 16649999
TI  - Brain lipid composition in postnatal iron-induced motor behavior alterations
      following chronic neuroleptic administration in mice.
AB  - Several studies have shown that deficient uptake or excessive break down of
      membrane phospholipids may be associated with neurodegenerative and psychiatric
      disorders. The purpose of the present study was to examine the effects of
      postnatal iron administration in lipid composition and behavior and whether or
      not the established effects may be altered by subchronic administration of the
      neuroleptic compounds, clozapine and haloperidol. In addition to motor activities
      such as locomotion, rearing and activity, a targeted lipidomics approach has been
      used to investigated the brains of eight groups of mice (four vehicle groups and
      four iron groups) containing six individuals in each group treated with vehicle,
      low dose clozapine, high dose clozapine and haloperidol. Lipids were extracted by
      the Folch method and analyzed using reversed-phase capillary liquid
      chromatography coupled on-line to electrospray ionization mass spectrometry
      (LC/ESI/MS). Identification of phosphatidylcholine (PC) and sphingomyelin (SM)
      molecular species was based on their retention time, m/z ratio, head group
      specific up-front fragmentation and analysis of the product ions produced upon
      fragmentation. A comparison between the Ve-groups and Fe-groups showed that
      levels of PC and SM molecular species and motor activities were significantly
      lower in Fe-Ve compared to Ve-Ve. The effects of neuroleptic treatment with and
      without iron supplementation were studied. In conclusion our results support the
      hypothesis that an association between psychiatric disorders and lipid and
      behavior abnormalities in the brain exists.

PMID- 16650000
TI  - Reconstitution in vitro of the GDP-fucose biosynthetic pathways of Caenorhabditis
      elegans and Drosophila melanogaster.
AB  - The deoxyhexose sugar fucose has an important fine-tuning role in regulating the
      functions of glycoconjugates in disease and development in mammals. The two
      genetic model organisms Caenorhabditis elegans and Drosophila melanogaster also
      express a range of fucosylated glycans, and the nematode particularly has a
      number of novel forms. For the synthesis of such glycans, the formation of GDP
      fucose, which is generated from GDP-mannose in three steps catalysed by two
      enzymes, is required. By homology we have identified and cloned cDNAs encoding
      these two proteins, GDP-mannose dehydratase (GMD; EC 4.2.1.47) and GDP-keto-6
      deoxymannose 3,5-epimerase/4-reductase (GER or FX protein; EC 1.1.1.271), from
      both Caenorhabditis and Drosophila. Whereas the nematode has two genes encoding
      forms of GMD (gmd-1 and gmd-2) and one GER-encoding gene (ger-1), the insect has,
      like mammalian species, only one homologue of each (gmd and gmer). This compares
      to the presence of two forms of both enzymes in Arabidopsis thaliana. All
      corresponding cDNAs from Caenorhabditis and Drosophila, as well as the previously
      uncharacterized Arabidopsis GER2, were separately expressed, and the encoded
      proteins found to have the predicted activity. The biochemical characterization
      of these enzymes is complementary to strategies aimed at manipulating the
      expression of fucosylated glycans in these organisms.

PMID- 16650001
TI  - Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through
      both extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt
      pathways.
AB  - Cartducin, a paralog of Acrp30/adiponectin, is a secretory protein produced by
      both chondrogenic precursors and proliferating chondrocytes, and belongs to a
      novel C1q family of proteins. We have recently shown that cartducin promotes the
      growth of both mesenchymal chondroprogenitor cells and chondrosarcoma-derived
      chondrocytic cells in vitro. However, the cartducin-signaling pathways
      responsible for the regulation of cell proliferation have not been documented. In
      this study, we examined whether cartducin exists in serum and further
      investigated the intracellular signaling pathways stimulated by cartducin in
      mesenchymal chondroprogenitor cells. Western blot analysis showed that, unlike
      Acrp30/adiponectin, cartducin was undetectable in mouse serum. Next, mesenchymal
      chondroprogenitor N1511 cells were stimulated with cartducin, and three major
      groups of mitogen-activated protein kinase (MAPK) pathways and the
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway were examined.
      Cartducin activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt,
      but not c-jun N-terminal kinase (JNK) nor p38 MAPK. The MEK1/2 inhibitor, U0126,
      blocked cartducin-stimulated ERK1/2 phosphorylation and suppressed the DNA
      synthesis induced by cartducin in N1511 cells. The PI3K inhibitor, LY294002,
      blocked cartducin-stimulated Akt phosphorylation and a decrease in cartducin
      induced DNA synthesis in N1511 cells was also observed. These data suggest that
      cartducin is a peripheral skeletal growth factor, and that the proliferation of
      mesenchymal chondroprogenitor cells stimulated by cartducin is associated with
      activations of the ERK1/2 and PI3K/Akt signaling pathways.

PMID- 16650002
TI  - Identification of RNase HII from psychrotrophic bacterium, Shewanella sp. SIB1 as
      a high-activity type RNase H.
AB  - The gene encoding RNase HII from the psychrotrophic bacterium, Shewanella sp.
      SIB1 was cloned, overexpressed in Escherichia coli, and the recombinant protein
      was purified and biochemically characterized. SIB1 RNase HII is a monomeric
      protein with 212 amino acid residues and shows an amino acid sequence identity of
      64% to E. coli RNase HII. The enzymatic properties of SIB1 RNase HII, such as
      metal ion preference, pH optimum, and cleavage mode of substrate, were similar to
      those of E. coli RNase HII. SIB1 RNase HII was less stable than E. coli RNase
      HII, but the difference was marginal. The half-lives of SIB1 and E. coli RNases
      HII at 30 degrees C were approximately 30 and 45 min, respectively. The midpoint
      of the urea denaturation curve and optimum temperature of SIB1 RNase HII were
      lower than those of E. coli RNase HII by approximately 0.2 M and approximately 5
      degrees C, respectively. However, SIB1 RNase HII was much more active than E.
      coli RNase HII at all temperatures studied. The specific activity of SIB1 RNase
      HII at 30 degrees C was 20 times that of E. coli RNase HII. Because SIB1 RNase
      HII was also much more active than SIB1 RNase HI, RNases HI and HII represent low
      and high-activity type RNases H, respectively, in SIB1. In contrast, RNases HI
      and HII represent high- and low-activity type RNases H, respectively, in E. coli.
      We propose that bacterial cells usually contain low- and high-activity type
      RNases H, but these types are not correlated with RNase H families.

PMID- 16650003
TI  - IPSE/alpha-1, a major secretory glycoprotein antigen from schistosome eggs,
      expresses the Lewis X motif on core-difucosylated N-glycans.
AB  - Schistosomes are parasitic flatworms that infect millions of people in
      (sub)tropical areas around the world. Glycoconjugates of schistosomes play a
      critical role in the interaction of the different developmental stages of the
      parasite with the host. In particular, glycosylated components of the eggs
      produced by the adult worm pairs living in the bloodstream are strongly
      immunogenic. We have investigated the glycosylation of interleukin-4-inducing
      factor from schistosome eggs (IPSE/alpha-1), a major secretory egg antigen from
      Schistosoma mansoni that triggers interleukin-4 production in human basophils, by
      MS analysis of tryptic glycopeptides. Nanoscale LC-MS(/MS) and MALDI-TOF(/TOF)-MS
      studies combined with enzymatic degradations showed that monomeric IPSE/alpha-1
      contains two N-glycosylation sites, which are each occupied for a large
      proportion with core-difucosylated diantennary glycans that carry one or more
      Lewis X motifs. Lewis X has been reported as a major immunogenic glycan element
      of schistosomes. This is the first report both on the expression of Lewis X on a
      specific schistosome egg protein and on a protein-specific glycosylation analysis
      of schistosome eggs.

PMID- 16650004
TI  - Biochemical characterization of the major sorghum grain peroxidase.
AB  - The major cationic peroxidase in sorghum grain (SPC4) , which is ubiquitously
      present in all sorghum varieties was purified to apparent homogeneity, and found
      to be a highly basic protein (pI approximately 11). MS analysis showed that SPC4
      consists of two glycoforms with molecular masses of 34,227 and 35,629 Da and it
      contains a type-b heme. Chemical deglycosylation allowed to estimate sugar
      contents of 3.0% and 6.7% (w/w) in glycoform I and II, respectively, and a mass
      of the apoprotein of 33,246 Da. High performance anion exchange chromatography
      allowed to determine the carbohydrate constituents of the polysaccharide chains.
      The N-terminal sequence of SPC4 is not blocked by pyroglutamate. MS analysis
      showed that six peptides, including the N-terminal sequence of SPC4 matched with
      the predicted tryptic peptides of gene indice TC102191 of sorghum chromosome 1,
      indicating that TC102191 codes for the N-terminal part of the sequence of SPC4,
      including a signal peptide of 31 amino acids. The N-terminal fragment of SPC4
      (213 amino acids) has a high sequence identity with barley BP1 (85%), rice Prx23
      (90%), wheat WSP1 (82%) and maize peroxidase (58%), indicative for a common
      ancestor. SPC4 is activated by calcium ions. Ca2+ binding increased the protein
      conformational stability by raising the melting temperature (Tm) from 67 to 82
      degrees C. SPC4 catalyzed the oxidation of a wide range of aromatic substrates,
      being catalytically more efficient with hydroxycinnamates than with tyrosine
      derivatives. In spite of the conserved active sites, SPC4 differs from BP1 in
      being active with aromatic compounds above pH 5.

PMID- 16650005
TI  - Phylogenetic comparison and classification of laccase and related multicopper
      oxidase protein sequences.
AB  - A phylogenetic analysis of more than 350 multicopper oxidases (MCOs) from fungi,
      insects, plants, and bacteria provided the basis for a refined classification of
      this enzyme family into laccases sensu stricto (basidiomycetous and
      ascomycetous), insect laccases, fungal pigment MCOs, fungal ferroxidases,
      ascorbate oxidases, plant laccase-like MCOs, and bilirubin oxidases. Within the
      largest group of enzymes, formed by the 125 basidiomycetous laccases, the gene
      phylogeny does not strictly follow the species phylogeny. The enzymes seem to
      group at least partially according to the lifestyle of the corresponding species.
      Analyses of the completely sequenced fungal genomes showed that the composition
      of MCOs in the different species can be very variable. Some species seem to
      encode only ferroxidases, whereas others have proteins which are distributed over
      up to four different functional clusters in the phylogenetic tree.

PMID- 16650006
TI  - Effect of casting procedures on screw loosening in UCLA-type abutments.
AB  - BACKGROUND: Screw loosening of implant restorations continues to be a
      complication in implant prosthodontics. Screw joints are subjected to a loss of
      initially applied torque because of friction and component misfit. It has been
      suggested that the loss of applied torque is less in machined metal abutments
      than in cast plastic abutments. PURPOSE: This study compared the loss of applied
      torque (detorque) values in machined titanium and in cast UCLA-type abutments for
      external hex abutment/implant interface. MATERIALS AND METHODS: Four groups of 12
      samples each were evaluated: (1) machined titanium abutments, (2) premachined
      palladium abutments cast with palladium, (3) plastic abutments cast with nickel
      chromium, and (4) plastic abutments cast with cobalt-chromium. Each abutment was
      torqued to 30 Ncm according to the manufacturer's instructions and detorqued
      three times. The mean loss of applied torque (detorque) was recorded as a
      percentage of the torque applied. Group means were calculated and compared using
      ANOVA and Tukey's LSD test. RESULTS: Mean detorque values were (1) 92.3 +/- 2.9%,
      (2) 81.6 +/- 5.0%, (3) 86.4 +/- 4.6%, and (4) 84.0 +/- 7.0%. Machined abutments
      demonstrated significantly greater detorque values compared with all cast groups
      (p < 0.05). No significant differences were found among cast groups. CONCLUSION:
      Machined abutments retained a significantly greater percentage of torque compared
      with cast abutments. Casting procedures decrease the percentage of applied
      torque, which may influence final screw joint stability.

PMID- 16650007
TI  - Histomorphologic characterization of noncarious and caries-affected
      dentin/adhesive interfaces.
AB  - PURPOSE: The purpose of this study was to compare the dentin/adhesive interfacial
      characteristics when bonding to noncarious as well as caries-affected dentin.
      MATERIALS AND METHODS: Seven extracted, unerupted, third molars were sectioned
      into halves. Artificial caries was created on one-half of each tooth, leaving the
      other half as a control. Dentin surfaces were treated with UNO adhesive according
      to the manufacturer's instructions for the wet-bonding technique and under
      environmental conditions present in the oral cavity. Dentin/adhesive interface
      sections of each half-tooth were stained with Goldner's trichrome, a classic bone
      stain, and examined using light microscopy. The width of exposed collagen was
      measured directly from photomicrographs, and adhesive penetration was analyzed
      qualitatively. RESULTS: The degree and extent to which the adhesive encapsulated
      the demineralized dentin matrix were reflected in the color difference in the
      stained sections with the noncarious dentin sections showing a degree of collagen
      encapsulation superior to that of the caries-affected dentin sections. The
      overall mean widths of exposed collagen were significantly (p < or = .05) greater
      at the caries-affected dentin/adhesive interface, 8.6 (1.7) microm, as compared
      with those at the noncarious dentin/adhesive interface, 6.0 (1.5) microm.
      CONCLUSIONS: The morphologic characteristics of the caries-affected
      dentin/interface suggest an increase in the exposed collagen zone and a decrease
      in the quality of the adhesive infiltration when compared with noncarious dentin.
      The evidence suggests that dentin substrate characteristics have a significant
      effect on the dentin/adhesive interface structure.

PMID- 16650008
TI  - Influence of abutment selection in maxillary Kennedy Class II RPD on elastic
      stress distribution in oral mucosa: an FEM study.
AB  - PURPOSE: The aim was to study the influence of abutment selection on elastic
      stress distribution in oral mucosa in a maxillary removable partial denture (RPD)
      by means of 3-dimensional finite element models. MATERIALS AND METHODS: Four RPD
      framework models of an equal size (by area) and underlying oral mucosa were
      produced for a Kennedy Class II arch. Each framework included an occlusal rest as
      part of a clasp assembly on one of four abutments (canine, first, and second
      premolars, and first molar) on the side contralateral to the edentulous ridge
      (tooth-supported side). Movement of the alveolar surface of the mucosa and the
      occlusal rest on the abutment adjacent to the ridge were fixed in a vertical
      direction. Movement of the rest on the tooth-supported side was restricted in all
      directions. Vertical or buccally oblique biting force was applied simultaneously
      on each of the locations representing three missing teeth. RESULTS: The
      frameworks with the contralateral side rest on the canine or the first premolar
      were less resistant to lateral forces than other framework designs, showing
      greater saddle displacements under the oblique force than the vertical force. The
      framework with the rest on the second premolar demonstrated relatively good
      resistance to deflection; however, both vertical saddle intrusion and the maximum
      equivalent stress in mucosa shown in all the models were within small ranges.
      CONCLUSION: The saddle movement was influenced by the abutment selection on the
      tooth-supported side, although resultant stress in the mucosa was insensitive to
      the abutment location.

PMID- 16650009
TI  - Pressure generated on a simulated mandibular oral analog by impression materials
      in custom trays of different design.
AB  - PURPOSE: The purpose was to measure the pressure exerted under a simulated
      mandibular edentulous impression at different locations using commonly used
      impression materials and four impression tray configurations. MATERIALS AND
      METHODS: This study was performed using an oral analog that simulated an
      edentulous mandibular arch. Three pressure transducers were embedded in the oral
      analog-one pressure transducer in the anterior ridge area, and the other two in
      the right and left buccal shelves. Four configurations of custom trays were
      fabricated: trays with no relief, with and without holes; and trays with relief,
      with and without holes. The impression materials tested were light body
      polysulfide, light body vinyl polysiloxane, medium body vinyl polysiloxane, and
      irreversible hydrocolloid. The custom tray and the oral analog were mounted using
      a reline jig, and a Satec universal testing machine was used to apply a constant
      pressure of 1 kg/cm(2) over a period of 5 minutes on the loaded custom tray.
      Eighty impressions for the 16 groups (n = 5) were made, and pressures were
      recorded every 10 seconds. Factorial ANOVA and Tukey Multiple Comparison Test
      were used to analyze the results (p < 0.05). RESULTS: A significant difference
      was found in the pressure produced using different impression materials.
      Irreversible hydrocolloid and medium body vinyl polysiloxane produced
      significantly higher pressure than light body polysulfide and light body vinyl
      polysiloxane impression materials. The presence of holes and/or relief
      significantly altered the magnitude of pressure produced by irreversible
      hydrocolloid and medium body vinyl polysiloxane but not light body polysulfide
      and light body vinyl polysiloxane. CONCLUSION: All impression materials produced
      pressure during simulated mandibular edentulous impression making. For making
      mandibular edentulous impressions, low-viscosity impression materials-light body
      polysulfide and light body vinyl polysiloxane-are recommended. Tray modification
      was not important in changing the amount of pressure produced for the low
      viscosity impression materials.

PMID- 16650010
TI  - Laser welding of cast titanium and dental alloys using argon shielding.
AB  - PURPOSE: This study investigated the effect of argon gas shielding on the
      strengths of laser-welded cast Ti and Ti-6Al-7Nb and compared the results to
      those of two dental casting alloys. MATERIALS AND METHODS: Cast plates of Ti, Ti
      6Al-7Nb, gold, and Co-Cr alloy were prepared. After polishing the surfaces to be
      welded, two plates were abutted and welded using Nd:YAG laser at a pulse duration
      of 10 ms, spot diameter of 1 mm, and voltage of 200 V. Five specimens were
      prepared for each metal by bilaterally welding them with three or five spots
      either with or without argon shielding. The failure load and percent elongation
      were measured at a crosshead speed of 1.0 mm/min. RESULTS: The factor of argon
      shielding significantly affected the failure load and elongation of the laser
      welded specimens. The failure loads of argon-shielded laser-welded CP Ti and Ti
      6Al-7Nb were greater compared with the failure loads of specimens welded without
      argon shielding for both three- and five-spot welding. Regardless of argon
      shielding, the failure loads of the laser-welded gold alloy were approximately
      half that of the control specimens. In contrast, the failure loads of the
      nonshielded laser-welded Co-Cr alloy were greater. The percent elongations
      positively correlated with the failure loads. CONCLUSIONS: The use of argon
      shielding is necessary for effective laser-welding of CP Ti and Ti-6Al-7Nb but
      not for gold and Co-Cr alloy.

PMID- 16650011
TI  - The effect of gingival retraction procedures on periodontal indices and
      crevicular fluid cytokine levels: a pilot study.
AB  - PURPOSE: The purpose of this study was to examine the effects of placement of
      retraction cord subgingivally upon periodontal indices including plaque index
      (PI), gingival index (GI), pocket depth (PD), bleeding on probing (BOP), and
      attachment level (AL), as well as gingival crevicular fluid (GCF) and TNF-alpha
      levels. METHODS: Ten teeth in 6 patients who were periodontally healthy were
      selected. These teeth had pocket depths of 3 mm or less, no evidence of
      significant loss of attachment, BOP, or plaque accumulation. The patients each
      received an oral prophylaxis. The following week, baseline measurements of
      periodontal indices and TNF-alpha were taken and the retraction cord was placed
      for 15 minutes. Following removal, the patients were dismissed. The periodontal
      indices measured included PI, GI, PD, BOP, and AL. In addition, the levels of TNF
      alpha in GCF, were investigated. These measurements were made before gingival
      retraction as a baseline and on the 1st, 3rd, 7th, 14th, and 28th days post
      retraction. RESULTS: A repeated measures ANOVA showed that TNF-alpha levels in
      GCF were significantly increased at all five intervals after gingival retraction
      compared to the baseline. The mean TNF-alpha level peaked at Day 1 (0.90 +/-
      0.62), then declined at Days 3 (0.53 +/- 0.16), 7 (0.43 +/- 0.08), 14 (0.47 +/-
      0.10), and 28 (0.43 +/- 0.08) but was still elevated 54% above baseline at Day
      28, p < 0.01. The GI was significantly elevated at Day 1 (0.9 +/- 0.49), p <
      0.01; Day 3 (0.53 +/- 0.32); and Day 7 (0.33 +/- 0.33), p < 0.05. Unlike TNF
      alpha, GI recovered to the baseline by day 14. Other periodontal parameters, PI,
      PD, BOP, and AL were not significantly altered by the gingival retraction
      procedure. CONCLUSION: This pilot study supports the previous research that
      gingival retraction causes an acute injury that heals clinically in 2 weeks as is
      indicated by the GI. It also provides the first evidence that gingival retraction
      results in an elevation of the proinflammatory cytokine, TNF-alpha, in GCF.

PMID- 16650012
TI  - Rehabilitation of a spark erosion prosthesis: a clinical report.
AB  - When complex prostheses are fabricated, it is expected that at some point
      maintenance will be necessary. This clinical report documents a 10-year-old
      maxillary spark erosion prosthesis that had been repaired many times, was
      discolored, and exhibited significant signs of wear. The metal superstructure was
      intact; therefore, only the acrylic resin base and teeth needed to be replaced.
      To reduce both cost and time without the prosthesis for the patient, the
      rehabilitation was completed within 24 hours.

PMID- 16650013
TI  - Use of stereolithographic templates for surgical and prosthodontic implant
      planning and placement. Part II. A clinical report.
AB  - Eight implants were placed in the posterior part of the mandible using computer
      generated stereolithographic templates. Preoperative implant simulation was done
      on a 3D computer model created by reformatted computerized tomography data. The
      surgeon and the prosthodontist positioned the simulated implants in the most
      favorable position addressing all concerns with regard to anatomy, biomechanics,
      and esthetics. The length and diameter of each implant along with the
      angulation/collar of abutments required for a screw-retained prosthesis were
      determined. Stereolithographic templates were then fabricated by incorporating
      the precise spatial position of the implants within the bone as previously
      planned during the computer simulation. The templates were fabricated to seat
      directly on the bone and were stable. The first template was used to complete
      osteotomies with a 2-mm twist drill followed by the second template for the 3-mm
      drill. Implants were placed and allowed to integrate for 4 months. After second
      stage surgery, the definitive abutments were torqued into place followed by
      insertion of the definitive screw-retained prostheses. Dimensions of all implants
      and abutments were the same as planned during the computer simulation.

PMID- 16650014
TI  - Communication between the dental laboratory technician and dentist: work
      authorization for fixed partial dentures.
AB  - PURPOSE: A questionnaire was sent to laboratory technicians to determine the
      level of communication between dentists and dental laboratories in specific areas
      of the work authorization forms for the fabrication of fixed partial dentures.
      MATERIALS AND METHODS: A select number of dental laboratories were randomly
      chosen from the National Association of Dental Laboratories (NADL) for each of
      the 50 states. The questionnaire was mailed to the laboratory directors for a
      total of 199 dental laboratories. The survey asked questions pertaining to the
      following areas of work authorization: legibility and thoroughness of
      prescriptions, patient information, choice of materials for the prosthesis,
      design of the prosthesis, and shade description. For each question, the number of
      responses received was tabulated and converted to a percentage. RESULTS: Of the
      199 laboratories surveyed, 114 (57%) responded to the questionnaire. Results from
      this survey suggest that there is lack of communication between dentists and
      dental laboratories through work authorization forms regarding choice of metal
      alloy, type of porcelain to be used, and choice of margin and pontic design for
      the prosthesis. CONCLUSIONS: Information obtained from the responding
      laboratories included effectiveness of work authorization forms. There were some
      similar trends indicated by the large percentage of dental laboratories agreeing
      on lack of communication by the dentists as reflected by the work authorization
      forms.

PMID- 16650015
TI  - The history of articulators: the wonderful world of "grinders." part I.

PMID- 16650016
TI  - 32 high-impact marketing tips for prosthodontists.

PMID- 16650020
TI  - Nursing and the EU Accession Process.

PMID- 16650023
TI  - The world needs urgent action on a huge scale: a conversation with Dr Jean Yan.

PMID- 16650024
TI  - INR authors speak out: caring for terminally ill family members in Latvia.

PMID- 16650025
TI  - The workplace is the issue - isn't it obvious?

PMID- 16650026
TI  - Our first international nursing conference: Chiang Mai, Thailand.

PMID- 16650027
TI  - Nurses at the forefront of innovation.
AB  - BACKGROUND: This paper is based on a presentation given by the author at the 23rd
      Quadrennial ICN Congress and 7th International Regulation Congress in Taipei in
      May 2005. AIM: Nurses worldwide are engaged in innovative practice on a daily
      basis. In most health systems across the world, nurses provide up to 80% of
      primary health care and are therefore well positioned to provide critically
      needed innovative solutions to many global health challenges. The aim of this
      paper is to increase awareness of the importance and value of innovations in
      nursing; provide an improved understanding of the contribution nurses make to
      innovation in health care; and increase understanding of the importance of
      creating environments that inspire innovation and help shape practice in new and
      improved ways. DESIGN: This paper explores the concept of innovation, the
      inherent set of characteristics that need to be present in order for innovations
      to succeed, and the barriers that impede innovation from occurring. CONCLUSION:
      There are numerous examples of successful innovations worldwide that are
      developed and implemented by nurses, some of which are described in this paper.
      The paper concludes that organizations need to have a support climate that
      encourages creativity and innovation to occur.

PMID- 16650028
TI  - The past, present and future of nurse education in Poland: stages, conditions and
      activities.
AB  - AIM: This paper describes the multidirectional activities recently completed to
      adapt nurse education in Poland to European standards. BACKGROUND: The Polish
      system transformation and the changes that have taken place in health care since
      the 1980s required intensive effort and change in the nursing care and education
      systems of nurses and midwives. OUTCOMES: Changes accomplished include: (1)
      preparation and implementation of a nurse education model complying with European
      standards; (2) discontinuance of the previous system of nurse education taught at
      the secondary school level; and (3) adjusting the organization and post-basic
      curricula of nurses and midwives to the actual needs of the society as well as
      for the nurses themselves. The goal of a uniform nurse education system in Poland
      that met European requirements motivated the Polish change agents. This change
      ensures the integration of Polish nurses with the nurses from Europe and other
      countries in their common endeavours to improve nursing care and health outcomes.
      CONCLUSIONS: The adopted changes in the system of nurse education resulted in
      uniformity of education and acceptance of bachelor's level education, which
      complies with European standards as well as adjusting the post-basic education to
      actual needs. Describing the substance and process of our work may be helpful to
      nurses in other countries who are working on their own models of nursing and
      health care restructuring.

PMID- 16650029
TI  - Improving international nurse training: an American-Italian case study.
AB  - BACKGROUND: Institutionalized international nurse training organized by national
      educational institutions is a relatively new phenomenon. This, descriptive case
      study examines an early example of an American-Italian initiative of such
      training, in order to stimulate future international education of nurses. AIM: To
      find out what factors have to be taken into account to improve training and what
      its potential effects are in exchange and also in the context of nurse migration.
      METHOD: A questionnaire was sent to the 85 nurses who all participated in this
      particular international programme (response rate: 30.6%). FINDINGS: The
      collected data indicate that personalized and well-aimed training, preparatory
      language courses, pre-departure exposure of nurses to the culture of the host
      country and well-prepared welcomes are among the most important ways to improve
      this programme. IMPLICATIONS FOR PRACTICE: While the specific circumstances and
      cultures involved in this particular case study should not be ignored, these
      factors might also be applied to maximize the positive effects of nurse
      migration. Two-way learning is among the positive effects of such an
      international training experience. Motivational and team-building effects can
      result in enhanced quality of care and a more efficient allocation of resources.
      However, the mind-opening effect seems to be the most important learning
      experience. Therefore, regardless of whether one system is considered better or
      worse than another, experiencing a different way of nursing/education is
      considered the most important, enriching element of an international learning
      experience. The effects of this experience could include avoiding cultural
      imposition in the increased cultural diversity of nursing in the country of
      origin.

PMID- 16650030
TI  - Nursing and midwifery research in Scotland: from partnership to collaboration.
AB  - Nurses and midwives form the workforce that provides the greatest proportion of
      direct care to service users. They have the ability to make a significant impact
      not only on the quality and outcomes of patient care, but also on service users'
      and carers' perceptions of the care experience. It is therefore vital that
      nursing and midwifery practice has a robust knowledge and evidence base. The
      Scottish Executive Health Department, in partnership with other key stakeholders,
      launched in 2004 an 8 million pounds funding package for research and development
      capacity and capability initiatives for nursing, midwifery and the allied health
      professions. This article seeks to describe the process of engagement and
      partnership building that enabled this scheme to be developed. It will attempt to
      illustrate how the convergence of political, policy and professional agendas has
      provided the opportunity for nurses and midwives to set a direction of travel for
      research and development that will enable them to become key players within
      multidisciplinary research at United Kingdom and international levels.

PMID- 16650031
TI  - Research priorities for nursing and midwifery in Southern Ireland.
AB  - AIM: To identify research priorities for nursing and midwifery in the Southern
      Health Board area in Ireland for the immediate and long term. METHOD: Ten focus
      groups were conducted over a 2-month period with 70 nurses and midwives working
      in clinical, managerial and educational roles participating. Based on focus group
      findings and a literature review a multi-item Likert type questionnaire was
      constructed and administered to 520 nurses and midwives (response rate 95%n=494).
      RESULTS: Research priorities were identified as: (1) impact of staff shortages on
      retention of RNs/RM's (80%); (2) quality of life of chronically ill patients
      (76%); (3) stress and bullying in the workplace (76%); (4) assessment and
      management of pain (75%); (5) skill mix and staff burnout (73%); (6) cardio
      pulmonary resuscitation decision making (72%); (7) coordination of care between
      hospital and primary care settings (69%); (8) medication errors (67%); and (9)
      promoting healthy lifestyles (64%). Respondents also indicated that these
      priorities warranted immediate attention. Implications for practice include the
      need for: (1) emphasis on quality pain control; (2) recognition and exploration
      of the ethical issues relating to resuscitation; and (3) management of the
      context within which clinical care is given.

PMID- 16650032
TI  - Caring for the terminally ill: experiences of Latvian family caregivers.
AB  - AIM: To increase understanding of the experiences and needs of family caregivers
      of terminally ill persons in Latvia. BACKGROUND: Latvia has high death rates from
      cardiovascular disease and cancer, and families care for the terminally ill with
      little preparation and support. Health professionals also have little preparation
      in supporting these patients and families at the end of life. METHODS: A
      qualitative study was carried out in the summer of 2004 in Latvia. Data
      collection was by semi-structured interviews with caregivers (n=18) whose care
      recipients died at least 1 year previously. FINDINGS: The caregiver narratives
      addressed experiences that paralleled the trajectory of the patient's illness:
      the disruption of normal life patterns; taking on the caregiver role;
      establishing new patterns and learning role competencies; engaging in preparation
      for dying; and the gains and losses of the caregiving experience as seen in
      retrospect. CONCLUSIONS: The caregiver narratives suggested a need for more
      education in practical caregiving; access to patient care equipment and supplies;
      and a need for ongoing support and guidance by knowledgeable medical personnel
      during caregiving.

PMID- 16650033
TI  - Hospice - the ideology and perspectives in Estonia.
AB  - BACKGROUND: Death and dying tend to be taboo for much of humankind. Themes about
      death and life ending have not been popular in Estonia because of its cultural
      traditions and history. AIMS: To describe the attitudes of Estonian professionals
      towards death and dying and to describe some future visions of hospice service in
      Estonia. METHODS: The theoretical view in this work comes from hospice conception
      and empirical data gained from structured interviews with professionals who are
      connected with dying people in their everyday work. FINDINGS: Some ideas of the
      hospice conception (e.g. pain control and psychosocial support) are used in
      hospitals and general care centres in Estonia, but there is little respect
      towards dying people and their needs. The idea of interdisciplinary teamwork is
      not in use.

PMID- 16650034
TI  - Detection of eating difficulties after stroke: a systematic review.
AB  - BACKGROUND: It is highly important in nursing care for persons with stroke to
      screen for, assess and manage eating difficulties. The impact on eating after
      stroke can be of different types, comprising dysphagia as well as eating
      difficulties in a larger perspective. Eating difficulties can cause complications
      such as malnutrition, dehydration, aspiration, suffocation, pneumonia and death.
      There is a lack of systematic reviews about methods to be used by nurses in their
      screening for eating difficulties. AIM: This review aims at systematically
      capturing and evaluating current peer-reviewed published literature about non
      instrumental (besides pulse oximetry) and non-invasive screening methods for
      bedside detection of eating difficulties among persons with stroke. METHODS: A
      search was performed in Medline and 234 articles were obtained. After a selection
      process 17 articles remained, covering seven screening methods and including
      about 2,000 patients. CONCLUSION: Best nursing practice for detecting eating
      difficulties includes as the first step the Standardized Bedside Swallowing
      Assessment (SSA) to detect dysphagia (strong evidence). As the second step an
      observation should be made of eating including ingestion, deglutition and energy
      (moderate evidence). Applying pulse oximetry simultaneously to SSA can possibly
      add to the accuracy of aspiration detection, especially silent aspiration
      (limited evidence). The methods should be used as a complement to interviews.

PMID- 16650035
TI  - Smoking among Greek nurses and their readiness to quit.
AB  - AIM AND RATIONALE: The preventable nature of smoking-associated diseases places a
      responsibility on health professionals for smoking-related health promotion. This
      paper disseminates information from a survey of qualified Greek nurses, comparing
      smoking attitudes, influences on smoking behaviours and desire to quit with their
      motivation to act as health promoters with patients and other health
      professionals who smoke. METHOD AND SAMPLE: A random sample (n=402) of qualified
      nurses employed by hospitals in Athens was surveyed with a self-administered
      questionnaire in a cross-sectional survey which had a 73% response rate.
      Following quality control measures, a final sample of 308 was achieved. RESULTS:
      Results showed that almost half of the nurses in the sample were current smokers,
      almost a quarter were former smokers, with just less than a third non-smokers.
      Using the Stages of Change model as a measure, the survey reported that 11% of
      the smokers in the sample expressed a desire to stop within the next month,
      another 12% in the coming 6 months and 23% of current smokers were still in the
      pre-contemplation stage. The main reasons given for continuing to smoke included
      using tobacco for enjoyment and as a coping mechanism for stress. Organizational
      problems were identified as the main source of stress. Finally, the majority of
      respondents confirmed the important part that they can play as role models in
      promoting health behaviours in their patients. CONCLUSIONS: Findings suggest that
      smoking prevalence among qualified Greek nurses is greater than that reported in
      the general Greek population. Implications and recommendations for nursing
      practice, education and research include the early provision of smoking education
      in nurse training. Interventions should be directed at nurses who smoke to assist
      them to stop and to maintain cessation according to their stages of change.

PMID- 16650037
TI  - 100 years of 'Allergy': can von Pirquet's word be rescued?
AB  - Summary It is 100 years since Clemens von Pirquet wrote his classic paper
      introducing the term 'allergy'. Although the word is no longer used in the way he
      intended, his concept of 'changed reactivity' laid the foundation for the modern
      science of immunology.

PMID- 16650038
TI  - Sweet talking-cellular carbohydrates and epithelial repair.

PMID- 16650039
TI  - Is the neutrophil a worthy target in severe asthma and chronic obstructive
      pulmonary disease?

PMID- 16650040
TI  - The role of probiotics in the management of allergic disease.
AB  - Probiotics have recently been advocated for the prevention and treatment of
      allergic disease (AD). In clinical practice they are increasingly being used for
      these purposes. Here we review the evidence base for the use of probiotics in the
      management of AD. We find support for their use in the treatment of childhood
      eczema, but the clinical significance of any treatment effect is uncertain. There
      is also evidence to support the use of probiotics in the prevention of childhood
      eczema. However the available evidence suggests that probiotics are not an
      effective treatment for allergic airway diseases. Probiotics may be more
      effective when used early in life, and they may have a particular role in
      gastrointestinal AD. The relative efficacy of different probiotic strains in the
      management of AD is not well established, and further work is needed to establish
      their mechanisms of action. In summary probiotics are likely to play a part in
      the management of childhood eczema in the future, and further studies are
      warranted to precisely define their role.

PMID- 16650041
TI  - Smoking and occupational asthma.
AB  - Cigarette smoking is a known risk factor for many chronic illnesses such as
      coronary heart and chronic obstructive pulmonary diseases. Smoking is often
      described as a risk factor for occupational asthma even though its effect on the
      development of asthma is still under debate and the links between smoking and
      occupational asthma, occupational rhinitis or occupational sensitization are
      elusive, controversial and contradictory. This review describes these
      relationships in a wide range of occupations, from laboratory, farm, brewery and
      hospital workers, to bakers, printers, cleaners, fish processors and others as
      observed in cross-sectional, cohort, and case-control studies published over the
      past thirty-five years i.e. from 1970 to 2005. Surprisingly, the data show there
      is little to support the view that the risk of occupational asthma is increased
      in workers who are smokers. However, evidence emerges of an increased risk of
      occupational sensitization in smoking workers exposed to several high and low
      molecular weight agents. This in-depth review confirms the relationship between
      smoking and occupational asthma is complex and contradictory. It deserves more
      attention and further studies, which need to be conducted without being
      influenced by selection bias or by the justifiable prejudice against smoking.

PMID- 16650042
TI  - Repair of the injury to respiratory epithelial cells characteristic of asthma is
      stimulated by Allomyrina dichotoma agglutinin specific serum glycoproteins.
AB  - BACKGROUND: The airway epithelium acts as a protective barrier, separating the
      external environment from the underlying tissue. Daily challenges result in
      damage to the epithelium that, in normal individuals, is quickly and effectively
      repaired. In respiratory diseases, such as asthma, this repair is compromised.
      Following injury to the epithelium, plasma leaks into the airway lumen acting as
      a protective protein cap. Carbohydrates are mediators of epithelial repair,
      however, the associated regulatory proteins remain unknown. OBJECTIVE: To
      identify mediators of epithelial repair based on their carbohydrate moieties
      using an in vitro wound repair culture model of human airway epithelial cells
      (1HAEo(-)). METHODS: Using the lectin Allomyrina dichotoma agglutinin (AlloA) as
      a tool, ligands essential in the repair of damaged epithelium were characterized.
      AlloA was subsequently used to purify and identify a glycoprotein associated with
      epithelial repair. RESULTS: The addition of AlloA to the media of mechanically
      wounded monolayers inhibited repair. Fetuin, a highly glycosylated serum protein,
      was identified as a glycoprotein bound by AlloA. The addition of fetuin to serum
      starved monolayers stimulated wound closure. CONCLUSION: These results indicate
      that following mechanical injury to the epithelium, serum glycoproteins, not only
      provide a protective barrier, but also are involved in the initiation of wound
      closure.

PMID- 16650043
TI  - Association between first-degree familial predisposition of asthma and atopy
      (total IgE) in newborns.
AB  - BACKGROUND: It is generally thought that infants with a first-degree familial
      predisposition of asthma are at higher risk of developing asthma than infants
      without predisposition. OBJECTIVE: To investigate whether there is an association
      between being at high risk for developing asthma and increased level of total IgE
      in newborns and whether total IgE is influenced by gender, family size, birth
      season, maternal smoking, birth weight, gestational age, and maternal diet.
      METHODS: Two hundred and twenty-one high risk and 308 low-risk infants were
      prenatally selected in a 5-year-period. Three to 5 days after birth, the total
      IgE was measured in capillary heel blood. RESULTS: Data on total IgE and first
      degree familial predisposition were available for 170 high-risk and 300 low-risk
      infants. There was a statistically significant relationship between being at high
      risk (maternal asthma) and increased levels of total IgE in newborns (total IgE
      cut-off levels: 0.6-0.9 IU/mL (odds ratio (OR)=2.1, 95% confidence interval (CI):
      1.2-3.7 to 3.0, 95% CI: 1.5-5.9)), between being born in autumn and increased
      levels of total IgE in newborns [total IgE cut-off levels: 0.5-0.6 IU/mL (OR=2.5,
      95% CI: 1.2-5.1 to 2.5, 95% CI: 1.2-5.4)] and between maternal vitamin
      supplements intake and decreased levels of total IgE in newborns (total IgE cut
      off level: 0.9 IU/mL (OR=0.5, 95% CI:0.3-1.0)). There was no interaction between
      the effects of maternal asthma and birth season on total IgE, as well as between
      the effects of maternal asthma and maternal vitamin supplements intake. Gender,
      family size, maternal smoking, birth weight, and gestational age did not
      influence the associations. CONCLUSION; Being at high-risk of asthma (maternal
      asthma) and birth season are positively associated with the presence of increased
      levels of total IgE at birth, whereas maternal vitamin supplements intake is
      negatively associated with the presence of total IgE at birth.

PMID- 16650044
TI  - ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese
      population.
AB  - BACKGROUND: Asthma is the most common chronic disorder in childhood, and asthma
      exacerbation is an important cause of childhood morbidity and hospitalization.
      Asthma is believed to be a complex disorder involving genetic and environmental
      factors, and several asthma susceptibility loci have been identified through
      genome-wide screening. A disintegrin and metalloprotease 33 (ADAM33) was the
      first asthma susceptibility gene to be discovered by positional cloning in 2002.
      OBJECTIVE: The aim of the present study was to investigate whether single
      nucleotide polymorphisms (SNPs) in ADAM33 are associated with childhood asthma in
      the Japanese population. METHODS: Twenty-three ADAM33 SNPs were genotyped by
      fluorescence correlation spectroscopy with the use of DNA from 155 families (538
      members) identified through children with atopic asthma. The transmission
      disequilibrium test (TDT) was performed for family-based association study.
      RESULTS: TDT revealed that minor alleles of S+1, ST+4, and T2 SNPs were over
      transmitted to asthma-affected offspring (P<0.05). According to the haplotype
      TDT, no haplotype of ADAM33 was transmitted preferentially to asthmatic
      offspring. CONCLUSION: Our results confirm the involvement of ADAM33 in the
      development of childhood asthma among the Japanese.

PMID- 16650045
TI  - Parity and decreased use of oral contraceptives as predictors of asthma in young
      women.
AB  - BACKGROUND: Asthma is more prevalent among males in childhood, but females report
      higher rates in adulthood. The reasons are unknown; although it has been
      hypothesized that hormonal factors may explain this sex-dependent risk of adult
      onset asthma. OBJECTIVE: To determine whether a woman's reproductive history or
      use of oral contraceptives is associated with adult-onset asthma. METHODS: In
      1991-1993, we surveyed 681 women aged 29-32 years randomly sampled from
      participants first surveyed at age 7 years by the 1968 Tasmanian Asthma Survey, a
      study of all children born in 1961 and attending school. Current asthma was
      defined as reporting asthma or wheezy breathing in the past 12 months. RESULTS:
      In women who did not have asthma or wheezy breathing by age 7 years, 13% had
      current asthma. The risk of current asthma in these who were parous increased
      with the number of births (odds ratio (OR) 1.50 per birth, 95% confidence
      interval (CI) 1.01-2.23 P=0.04) while women with one birth were at a lower risk
      than nulliparous women (OR 0.46 95% CI 0.2-1.06, P=0.07). Independent of parity,
      the risk decreased by 7% (95% CI 0-13%) per year of oral contraceptive pill use
      in all women. In women who did have asthma or wheezy breathing by age 7 years,
      neither reproductive history nor oral contraceptive pill use predicted current
      asthma. CONCLUSION: Our observation that parity and decreased oral contraceptive
      use predict asthma in women, is consistent with the hypothesis that the asthma
      that develops after childhood is in part a response to endogenous and exogenous
      female hormones. This may be due to alterations of cytokine responses by the
      pregnant state, triggering adult-onset asthma in women.

PMID- 16650046
TI  - Transforming growth factor-beta and interleukin-10 in breast milk and development
      of atopic diseases in infants.
AB  - BACKGROUND: Precise relationship between breastfeeding and infant allergy is
      poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in
      colostrum and mature milk from allergic and non-allergic mothers and to verify
      relationship with allergic disease development. METHODS: Mothers (13 allergics,
      nine controls) of 22 newborns participated to prospective study on development of
      children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10
      by ELISA. Children underwent paediatrician evaluation at 6 months of life.
      RESULTS: Data are presented as median values and range. A significant difference
      in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and
      mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic
      mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic
      (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL)
      (P=0.015). IL-10 was weakly expressed without significant differences between
      allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature
      milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0
      42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but
      none from controls, presented atopic dermatitis. CONCLUSION: TGF-beta(1) was
      significantly less secreted in mature milk of allergic mothers, while no
      difference in IL-10 was found. Particular cytokine patterns in milk could
      influence development of atopic diseases. Further immunological studies in this
      field are necessary.

PMID- 16650047
TI  - Cytokine responses to allergens during the first 2 years of life in Estonian and
      Swedish children.
AB  - BACKGROUND: The prevalence of atopic disease among children in the formerly
      socialist countries in Europe, with a life style similar to that prevailing in
      Western Europe 30-40 years ago, is low, whereas there has been a pronounced
      increase in industrialized countries over the last decades. The environment
      during infancy influences the risk of developing allergy for many years, perhaps
      even for life. OBJECTIVE: To investigate the development of allergen-specific
      cytokine responses during the first 2 years of life in two geographically
      adjacent countries with marked differences in living conditions and incidence of
      atopic diseases, i.e. Estonia and Sweden. METHODS: The development of immune
      responses to food (beta-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant
      (cat and birch) allergens was studied from birth up to the age of 2 years in 30
      Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were
      performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months.
      RESULTS: The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood
      mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and
      Swedish infants declined during the first 3 months of life. All cytokines then
      progressively increased in the Swedish infants, indicating the replacement of non
      specifically responding immature cord blood T cells with specific T memory cells,
      which are primed postnatally. The resurgence of allergen-specific responses in
      the Estonian infants was less marked. These differences were particularly notable
      for birch-specific T cell responses, which correlated with development of atopic
      disease in the Swedish children. CONCLUSIONS: The development of specific T cell
      memory to food and inhalant allergens during the first 2 years of life differs
      between infants living in Sweden and Estonia, and mirrors the disparate patterns
      of expression of allergic disease which subsequently develops in the respective
      populations.

PMID- 16650048
TI  - Is the effect of probiotics on atopic dermatitis confined to food sensitized
      children?
AB  - BACKGROUND: Probiotics have previously been shown to reduce the severity of
      atopic dermatitis (AD) in infants and children. OBJECTIVE: To examine the effect
      of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on
      established AD in children. SUBJECTS AND METHODS: Atopic children with current
      dermatitis received 2 x 10(10) colony forming units/g of probiotic (n=29) or
      placebo (n=30). Both were given daily as a powder mixed with food or water.
      SCORing Atopic Dermatitis (SCORAD; developed by the European Task Force on Atopic
      Dermatitis) a measure of the extent and severity of AD, was assessed at baseline,
      2 and 12 weeks after starting treatment and 4 weeks after treatment was
      discontinued. RESULTS: SCORAD geometric mean score at baseline was 26.0 (21.9
      30.8) in the probiotic group and 35.1 (28.9-42.8) in the placebo group (P=0.02).
      After adjustment for these between-group baseline differences there was no
      significant improvement in AD at 12 weeks, SCORAD geometric mean ratio: 0.80 (95%
      confidence level (CI) 0.62-1.04, P=0.10). Among the food sensitized children,
      there was an improvement in those treated with probiotics, SCORAD geometric mean
      ratio: 0.73 (95% CI 0.54-1.00, P=0.047). CONCLUSION: In this study a combination
      of Lactobacillus rhamnosus and Bifidobacteria lactis improved AD only in food
      sensitized children.

PMID- 16650049
TI  - Acute infections, infection pressure, and atopy.
AB  - BACKGROUND: During the recent years, a new theory postulating that lack of early
      childhood infections would increase the prevalence rate of allergies has rapidly
      gained momentum. This hygiene hypothesis has been widely disseminated to the
      general public and it has been suggested that vaccinations would accordingly
      indirectly increase rates of atopy. We thus investigated associations between
      acute infections, infection pressure (i.e. number of daily child contacts) and
      atopy in one of the largest population-based medical surveys ever published in
      the medical literature. METHODS: Almost all Finns born between 1976 and 1984 and
      a sample of older teenagers aged up to 19 years (n=5 47 190) were vaccinated and
      questioned to establish clinical history of mumps and rubella and manifestations
      of atopy (rhinoconjunctivitis, eczema, and asthma) in 1982-1986. A subsample
      (n=37 733) including all those subjects who were vaccinated during the first 2
      months of the measles, mumps, and rubella (MMR) programme were also queried
      information about upper respiratory infections (URIs) and infection pressure.
      Crude and adjusted prevalence ratios of atopy among those with infectious disease
      history compared with those without it were calculated. RESULTS: The risk of URI
      and a history of mumps and rubella increased with the number of daily contacts.
      This association was apparent especially among the youngest subjects with regard
      to URIs whereas the proportion with histories of mumps and rubella increased with
      increasing infection pressure more clearly among the 6-year-olds. Atopy was not
      associated with daily child contacts among pre-schoolers. Children with histories
      of repeated URIs and MMR diseases had substantially more atopy than those with
      lower URI or MMR disease rates. CONCLUSIONS: Atopic subjects seem to be
      especially prone to clinically apparent acute respiratory tract infections, and
      might be in particular need of protection by immunizations. This study does not
      support the idea that the prevalence of atopy in affluent countries would be
      affected from disappearing respiratory tract infections.

PMID- 16650050
TI  - Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in
      urban South African children.
AB  - BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic
      disease, both associated with a T-helper (Th) 2 immune response, is
      controversial, as it has been reported that helminth infection may either
      suppress or pre-dispose to atopic disease. This relation has not been tested in
      an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known
      Th1-stimulating infection. OBJECTIVE: To study the association of intestinal
      helminth infection and atopic disease in a community where helminth infection is
      endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly
      selected children aged 6-14 years from a poor urban suburb were tested with
      allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris
      specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal
      helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was
      tested in the group of children aged 10 years and older. RESULTS: were corrected
      for demographic variables, socioeconomic status, parental allergy, environmental
      tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and
      for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of
      children, Ascaris eggs were found in 15% and TST was positive in 53%. Children
      with elevated Ascaris-sIgE had significantly increased risk of positive SPT to
      aeroallergens, particularly house dust mite, atopic asthma (ever and recent),
      atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper
      responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was
      associated with significantly increased risk of atopic symptoms (adjusted odds
      ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those
      with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI
      0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris
      (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to
      mild Ascaris infection and that MTB infection may be protective against this
      risk, probably by stimulation of anti-inflammatory networks.

PMID- 16650051
TI  - Towards profiling the gene expression of fibroblasts from atopic dermatitis
      patients: human 8K complementary DNA microarray.
AB  - BACKGROUND: High-throughput technologies, including DNA-chip array, have been
      used to search for the genes that are dysregulated in human diseases. The atopic
      dermatitis (AD)-associated genes are gradually being reported; however, the
      differentially altered gene expression profiles of atopic fibroblasts have not
      been well elucidated. OBJECTIVE: We wanted to gain more insights into AD and to
      find candidate genes, especially in regards to the role of fibroblasts in the
      pathogenesis of AD. METHODS: cDNA microarray (8K) profiling of the primary
      cultured AD patients-derived fibroblasts was conducted by a pooling method of the
      recruited 22 normal controls, the 10 extrinsic type (ADe) patients and the 10
      intrinsic type (ADi) patients. SAM analysis of the microarray results (2-fold cut
      off) was conducted to select the candidate genes. Quantification by real-time
      PCRs confirmed the array data in the randomized paired samples (normal vs. ADe
      n=10; normal vs. ADi n=10). RESULTS: We listed the 22 up-regulated and 95 down
      regulated genes in the AD fibroblasts. Real-time PCR results showed that several
      genes such as hyaluronan synthase 2 (HAS2), TNF-alpha-induced protein 6 (TNFAIP6)
      and IL-8 were matched with the array results with statistical significance.
      CONCLUSION: These results suggest gene expression profiles that are associated
      with AD and this implied that fibroblasts may play important roles in the AD
      pathogenesis. We provided new insights into three candidate genes such as HAS2,
      TNFAIP6 and IL-8 with respect to their involvement in AD disease.

PMID- 16650052
TI  - Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition?
AB  - BACKGROUND: Ragweed and mugwort have nearly identical flowering periods. Clinical
      and serological studies showed that ragweed and mugwort sensitization are often
      associated and this poses relevant clinical problems in patients for whom
      specific immunotherapy is warranted. OBJECTIVE: To establish whether the
      concurrent ragweed and mugwort pollen hypersensitivity is the result of co
      sensitization or of co-recognition by using purified recombinant allergens.
      METHODS: Sensitization to ragweed and mugwort pollen was assessed by skin prick
      test (SPT) in all patients reporting allergic symptoms in August and September.
      IgE reactivity of sera from 42 patients (26 Amb+/Art+, 14 Amb+/Art-, and two Amb
      /Art+) to ragweed and mugwort pollen extract as well as to several recombinant
      ragweed (rAmb a 1, rAmb a 5, rAmb a 6, rAmb a 8, rAmb a 9, and Amb a 10) and
      mugwort (rArt v 1, rArt v 4, rArt v 5, rArt v 6, and three EF-hand calcium
      binding protein) allergens was detected by dot-blot and ELISA analyses. RESULTS:
      IgE reactivity of 372 weed pollen-allergic patients was studied. Mugwort
      reactivity was strongly associated with ragweed hypersensitivity: only 10/147
      (7%) mugwort-hypersensitive patients were not sensitized to ragweed, whereas
      225/362 (62%) ragweed-hypersensitive patients were not sensitized to mugwort. In
      vitro, 90% of ragweed-allergic patients reacted with rAmb a 1. Reactivity to
      other ragweed allergens ranged between 20% and 35%. Forty-six percent of the
      mugwort-sensitized patients recognized rArt v 1%, 25% reacted to Art v 4, Art v
      5, and Art v 6, and 7% recognized the three-EF hand calcium-binding protein.
      Immunoblot inhibition experiments showed that pre-incubation with ragweed pollen
      extract only weakly decreased IgE reactivity to mugwort allergens. CONCLUSION:
      Patients showing both ragweed- and mugwort-positive SPT and/or RAST are co
      sensitized. Future studies will establish whether IgE reactivity translates into
      clinical symptoms and, hence, if co-sensitized patients should undergo specific
      immunotherapy with extracts of both mugwort and ragweed pollen.

PMID- 16650053
TI  - The role of profilin and lipid transfer protein in strawberry allergy in the
      Mediterranean area.
AB  - BACKGROUND: In contrast to other Rosaceae fruit, only few cases of patients with
      adverse reactions to strawberry are listed in literature. OBJECTIVE To identify
      allergenic proteins in strawberry and to express and characterize recombinant
      strawberry lipid transfer protein (LTP; rFra a 3). METHODS: Established apple
      allergic patients were recruited on the basis of a reported allergic reaction to
      strawberry (n=28, confirmed by double-blind placebo-controlled food challenge in
      four patients) or on the basis of IgE reactivity to LTP (n=34). Sensitization to
      purified natural and recombinant allergens was assessed by RAST, immunoblot
      (inhibition) and basophil histamine release (BHR). A strawberry cDNA library was
      screened for genes homologous to known fruit allergens. Fra a 3 was cloned and
      expressed in the yeast Pichia pastoris and compared with peach and apple LTP by
      RAST, immunoblot-inhibition and BHR tests. RESULTS: Genes homologous to Bet v 1,
      Bet v 6, profilin and LTP were identified in a strawberry cDNA library. In BHR
      the rFra a 3 induced histamine release at a 100-fold higher concentration than
      peach LTP. RAST inhibition showed high cross-reactivity to peach and apple LTP,
      although IgE reactivity was lower by a factor 5. On strawberry immunoblot,
      patients' IgE showed reactivity to a Bet v 1 homologue, profilin, LTP and high
      molecular weight bands. CONCLUSION: In addition to a Bet v 1 homologue,
      strawberry also contains IgE-binding profilin and LTP. The rFra a 3 has less
      allergenic potency than peach and apple LTP, and therefore is an interesting tool
      for future immunotherapy. Fra a 3 does not seem to be clinically relevant.

PMID- 16650054
TI  - Effects of levocetirizine as add-on therapy to fluticasone in seasonal allergic
      rhinitis.
AB  - BACKGROUND: Addition of H(1) antagonists to intranasal corticosteroid treatment
      of allergic rhinitis (AR) is common in clinical practice and recommended by
      guidelines, despite some evidence that the additive benefits are negligible.
      OBJECTIVE: To assess additional benefits of 5 mg levocetirizine dihydrochloride
      in seasonal AR patients using 200 mcg fluticasone propionate nasal spray once
      daily. METHODS: In a double-blind placebo-controlled crossover study of 27
      patients, following 2 weeks without treatment, subjects used fluticasone with
      levocetirizine or identical placebo for 2 weeks each. Assessments were the
      Juniper mini Rhinoconjunctivitis Quality-of-Life Questionnaire (mini-RQLQ),
      domiciliary peak nasal inspiratory flow (PNIF), total nasal symptoms (TNS) scores
      and nasal nitric oxide concentrations. Effects were interpreted and tested
      against minimal clinically important differences. RESULTS: Add-on effects for
      levocetirizine vs. placebo excluded any clinically significant benefits: mean
      effects (one sided 95% confidence intervals) were mini-RQLQ -0.11 (-0.34), PNIF
      +0.57 (+5.23), and TNS -0.11 (-0.60). Numbers needed to treat (95% confidence
      intervals) by outcome were mini-RQLQ 14 (5 to 49), PNIF 4 (3-7), and TNS 3 (2-6).
      No significant within or between treatment effects were seen for nasal nitric
      oxide. CONCLUSION: Contrary to current practice, the present results demonstrate
      that for the majority of patients, antihistamine add-on to effective nasal
      steroid treatment is inappropriate. Further work is required to confirm that this
      is also true in the most severe cases, and the available evidence needs to be put
      into guidelines and implemented.

PMID- 16650073
TI  - Non-syndromic, autosomal-recessive deafness.
AB  - Non-syndromic deafness is a paradigm of genetic heterogeneity with 85 loci and 39
      nuclear disease genes reported so far. Autosomal-recessive genes are responsible
      for about 80% of the cases of hereditary non-syndromic deafness of pre-lingual
      onset with 23 different genes identified to date. In the present article, we
      review these 23 genes, their function, and their contribution to genetic deafness
      in different populations. The wide range of functions of these DFNB genes
      reflects the heterogeneity of the genes involved in hearing and hearing loss.
      Several of these genes are involved in both recessive and dominant deafness, or
      in both non-syndromic and syndromic deafness. Mutations in the GJB2 gene encoding
      connexin 26 are responsible for as much as 50% of pre-lingual, recessive
      deafness. By contrast, mutations in most of the other DFNB genes have so far been
      detected in only a small number of families, and their contribution to deafness
      on a population scale might therefore be limited. Identification of all genes
      involved in hereditary hearing loss will help in our understanding of the basic
      mechanisms underlying normal hearing, in early diagnosis and therapy.

PMID- 16650074
TI  - Views of female breast cancer patients who donated biologic samples regarding
      storage and use of samples for genetic research.
AB  - Although social and ethical issues related to the storage and use of biologic
      specimens for genetic research have been discussed extensively in the medical
      literature, few empiric data exist describing patients' views. This qualitative
      study explored the views of 26 female breast cancer patients who had consented to
      donate blood or tissue samples for breast cancer research. Participants generally
      did not expect personal benefits from research and had few unprompted concerns.
      Few participants had concerns about use of samples for studies not planned at the
      time of consent. Some participants did express concerns about insurance or
      employment discrimination, while others believed that current privacy protections
      might actually slow breast cancer research. Participants were generally more
      interested in receiving individual genetic test results from research studies
      than aggregate results. Most participants did not want individual results of
      uncertain clinical significance, although others believed that they should be
      able to receive such information. These data examined the range of participants'
      views regarding the storage and use of biologic samples. Further research with
      different and diverse patient populations is critical to establishing an
      appropriate balance between protecting the rights of human subjects in genetic
      research and allowing research to progress.

PMID- 16650075
TI  - Loss of function mutations in SIL1 cause Marinesco-Sjogren syndrome.

PMID- 16650076
TI  - The beat goes on: ciliary proteins are defective in Meckel syndrome.

PMID- 16650077
TI  - Gene discovery in methylmalonic aciduria and homocystinuria.

PMID- 16650078
TI  - Novel germline mutations in the APC gene of Cypriot patients with familial and
      sporadic adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is one of the two commonest familial
      syndromes that predispose to colorectal cancer. FAP is caused by mutations in the
      adenomatous polyposis coli (APC) tumour suppressor gene that has a high
      penetrance. The disease is characterized by the occurrence of hundreds to
      thousands of colorectal polyps, which if left untreated give rise to colorectal
      cancer. In Cyprus, there are no molecular data available as yet on families with
      FAP. This work presents the results of APC analysis in our population for the
      first time. The APC gene was analyzed in 33 DNA samples from 20 individuals
      belonging to four FAP families and 13 patients with sporadic polyposis. We
      identified three truncating mutations, four missense mutations and 11
      polymorphisms. It is of interest that two of the three truncating mutations,
      2307delA and Q1242X, are novel, which supports the existence of a unique genetic
      pool in the Cypriot population. This ethnic molecular study in addition to
      highlighting population heterogeneity also contributes to phenotype-genotype
      associations that are essential for the clinical management of FAP families in
      Cyprus.

PMID- 16650079
TI  - High prevalence of the IVS 1 + 1 G to A/GJB2 mutation among Czech hearing
      impaired patients with monoallelic mutation in the coding region of GJB2.
AB  - Biallelic pathogenic GJB2 gene mutations cause pre-lingual genetic hearing loss
      in up to 50% of individuals with bilateral sensorineural hearing loss worldwide.
      Sequencing of the entire GJB2 gene-coding region in Czech patients with pre
      lingual bilateral hearing loss revealed that 10.3% of Czech patients carry only
      one monoallelic pathogenic mutation in the coding region of the GJB2 gene, which
      is significantly more than the population frequency of 3.4%. The 309-kb GJB6
      deletion, frequent in Spain and France, is very rare in the Czech population. In
      order to evaluate the impact of the IVS1 + 1 G to A splice site mutation in the
      non-coding part of the GJB2 gene among Czech patients, we tested all available
      patients with pre-lingual hearing loss with only one monoallelic mutation in the
      coding part of GJB2. By sequencing of the exon 1 region of the GJB2 gene and HphI
      restriction analysis in 20 Czech patients we identified nine patients carrying
      IVS1 + 1 G to A. Testing for this mutation explained deafness in 45% of Czech
      GJB2 monoallelic patients. This mutation represents now 4% of GJB2 pathogenic
      mutations in Czech patients and is the third most common GJB2 mutation found in
      our cohort of 242 unrelated Czech patients with prelingual hearing loss. A
      similar frequency may also be expected in other Central European or Slavic
      populations.

PMID- 16650080
TI  - Expanding the phenotypic spectrum of L1CAM-associated disease.
AB  - Mutations in the L1CAM gene cause neurological abnormalities of variable
      severity, including congenital hydrocephalus, agenesis of the corpus callosum,
      spastic paraplegia, bilaterally adducted thumbs, aphasia, and mental retardation.
      Inter- and intrafamilial variability is a well-known feature of the L1CAM
      spectrum, and several patients have a combination of L1CAM mutations and
      Hirschsprung's disease (HSCR). We report on two siblings with a missense mutation
      in exon 7 (p.P240L) of the L1CAM gene. In one of the siblings, congenital
      dislocation of the radial heads and HSCR were present. Neither patient had
      hydrocephalus, adducted thumbs, or absent speech, but both had a hypoplastic
      corpus callosum. We suggest that L1CAM mutation testing should be considered in
      male patients with a positive family history compatible with X-linked inheritance
      and either the combination of agenesis of the CC and HSCR or the combination of
      agenesis of the CC and limb abnormalities, including abnormalities other than
      adducted thumbs.

PMID- 16650081
TI  - Genetic architecture of the F7 gene in a Spanish population: implication for
      mapping complex diseases and for functional assays.
AB  - Delineating the genetic variability of loci coding for complex diseases helps to
      understand the individual variation in disease susceptibility and drug response.
      We present the allelic architecture of the F7 gene. This gene is the major
      determinant of FVII plasma levels, and these plasma levels constitute an
      important intermediate risk factor for cardiovascular disease. As part of the
      Genetic Analysis of Idiopathic Thrombophila Project, we completely re-sequenced
      the F7 locus (promoter, exons, introns, and 3'-untranslated region) in 40
      unrelated individuals. We found 49 polymorphisms with only two amino acid changes
      suggesting that regulatory non-coding and intronic variants are responsible for
      the FVII variability. These results are important for mapping susceptibility
      alleles of complex diseases, because differences in pair-wise linkage
      disequilibrium patterns between DNA variants and haplotype frequency
      distributions may help to detect disease-associated alleles. In addition, we
      present the results of an in silico search that established genomic comparisons
      among different species. In conclusion, our study of the F7 DNA sequence
      variations is an example of a strategy for analyzing the genetic architecture of
      a quantitative trait locus. Furthermore, it provides a model for future analyses
      of genetic factors that contribute to the susceptibility of complex diseases in
      humans.

PMID- 16650082
TI  - The mapping of DFNB62, a new locus for autosomal recessive non-syndromic hearing
      impairment, to chromosome 12p13.2-p11.23.
AB  - Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common
      form of prelingual inherited hearing impairment (HI). Here is described the
      mapping of a novel ARNSHI locus in a consanguineous Pakistani family with
      profound congenital HI. Two-point and multipoint linkage analyses were performed
      for the genome scan and fine mapping markers. Haplotypes were constructed to
      determine the region of homozygosity. At theta = 0, the maximum two-point LOD
      score of 4.0 was obtained at marker AAC040. A maximum multipoint LOD score of 5.3
      was derived at marker D12S320, with the three-unit support interval demarcated by
      D12S89 and D12S1042. The region of homozygosity is flanked by markers D12S358 and
      D12S1042, which corresponds to 22.4 cM according to the Rutgers combined linkage
      physical map of the human genome and spans 15.0 Mb on the sequence-based physical
      map. A novel ARNSHI locus DFNB62 was mapped to chromosome 12p13.2-p11.23. DFNB62
      represents the second ARNSHI locus to map to chromosome 12.

PMID- 16650083
TI  - Genotype-phenotype correlation of R870H mutation in hypertrophic cardiomyopathy.

PMID- 16650084
TI  - Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families.

PMID- 16650085
TI  - Hemizygosity for chromosome 2q14.2-q22.1 spanning the GLI2 and PROC genes
      associated with growth hormone deficiency, polydactyly, deep vein thrombosis and
      urogenital abnormalities.

PMID- 16650086
TI  - Screening of the CAPN3 gene in patients with possible LGMD2A.

PMID- 16650087
TI  - Letter to the Editor in response to Duncan RE and Delatycki MB. Predictive
      genetic testing in young people for adult-onset conditions: where is the
      empirical evidence?

PMID- 16650090
TI  - Cholesteryl ester transfer protein gene mutations in Brazilian
      hyperalphalipoproteinemia.

PMID- 16650091
TI  - The local lymph node assay and skin sensitization: a cut-down screen to reduce
      animal requirements?
AB  - The local lymph node assay (LLNA), an alternative approach to skin-sensitizing
      testing, has made a significant contribution to animal welfare by permitting a
      reduction and refinement of animal use. Although there is clearly an aspiration
      to eliminate the use of animals in such tests, it is appropriate also to consider
      other opportunities for refinement and reduction of animal use. We have therefore
      explored the use of a modified version of the LLNA for screening purposes when
      there is a need to evaluate the sensitizing activity of a large number of
      chemicals, as will be the case under the auspices of registration, evaluation and
      authorization of chemicals (REACH). Using an existing LLNA database of 211
      chemicals, we have examined whether a cut-down assay comprising a single high
      dose group and a concurrent vehicle control would provide a realistic approach
      for screening chemicals for sensitizing potential. The analyses reported here
      suggest this is the case. We speculate that the animal welfare benefits may be
      enhanced further by reducing the number of animals per experimental group.
      However, a detailed evaluation will be necessary to provide reassurance that a
      reduction in group size would provide adequate sensitivity across a range of skin
      sensitization potencies.

PMID- 16650092
TI  - Application of HEMA on intact mouse skin--effects on the immune system.
AB  - Previously, we have shown that 2-hydroxyethylmethacrylate (HEMA) can bind to
      protein and that autoantibodies were induced in mice by immunization with a self
      protein in vitro conjugated with HEMA. The present study aimed to develop a model
      for HEMA-induced sensitivity by the application of the substance on intact skin.
      Female BALB/c mice were painted on the dorsum of each ear with 50% HEMA in
      vehicle twice a week for 6 weeks. The anti-CD3epsilon-stimulated lymph node
      production and the spontaneous spleen-cell production of the cytokines
      interleukin (IL)-2, IL-4, IL-6, IL-10 and interferon-gamma were assessed by
      enzyme-linked immunosorbent assay. In another experiment, the cytokines were
      followed after subcutaneous HEMA injections. Animals painted with HEMA had a
      significantly higher IL-6 production by anti-CD3epsilon-stimulated lymph node
      cells and significantly suppressed IL-10 production by spleen cells compared to
      vehicle-treated mice. This correlated to some extent with the spontaneous spleen
      cell production induced by subcutaneously administered HEMA. An injection of 20
      micromol of HEMA induced an increased production of IL-6, while injection of 40
      micromol depressed both IL-6 and IL-10 production. Although there was no sign of
      inflammation on the ears, findings suggest that HEMA had penetrated the skin and
      induced a reaction in the immune system.

PMID- 16650093
TI  - Comparison of elicitation potential of chloroatranol and atranol--2 allergens in
      oak moss absolute.
AB  - Chloroatranol and atranol are degradation products of chloroatranorin and
      atranorin, respectively, and have recently been identified as important contact
      allergens in the natural fragrance extract, oak moss absolute. Oak moss absolute
      is widely used in perfumery and is the cause of many cases of fragrance allergic
      contact dermatitis. Chloroatranol elicits reactions at very low levels of
      exposure. In oak moss absolute, chloroatranol and atranol are present together
      and both may contribute to the allergenicity and eliciting capacity of the
      natural extract. In this study, 10 eczema patients with known sensitization to
      chloroatranol and oak moss absolute were tested simultaneously to a serial
      dilution of chloroatranol and atranol in ethanol, in equimolar concentrations
      (0.0034-1072 microM). Dose-response curves were estimated and analysed by
      logistic regression. The estimated difference in elicitation potency of
      chloroatranol relative to atranol based on testing with equimolar concentrations
      was 217% (95% confidence interval 116-409%). Both substances elicited reactions
      at very low levels of exposure. It is concluded that the differences in
      elicitation capacity between the 2 substances are counterbalanced by exposure
      being greater to atranol than to chloroatranol and that both substances
      contribute to the clinical problems seen in oak moss absolute-sensitized
      individuals.

PMID- 16650094
TI  - Contact allergy to herbal teas derived from Asteraceae plants.
AB  - Contact allergy to herbal teas derived from the Asteraceae plant family was
      investigated in patients allergic to sesquiterpene lactones (SLs). 20 patients
      with a known contact allergy to SLs were recalled and patch tested with aqueous
      extracts of 8 different herbal teas based on Asteraceae plants as well as with
      parthenolide and other SLs. In 18 of 20 patients with SL allergy, there were
      positive test reactions to the Asteraceae teas, mainly to those based on German
      chamomile, dandelion and wormwood. Among the SLs, parthenolide was the most
      frequent co-reactor. Obviously, most patients with a contact allergy to SLs are
      allergic to commercial teas derived from the Asteraceae plant family as well.

PMID- 16650095
TI  - Primary prevention in health care employees: a prospective intervention study
      with a 3-year training period.
AB  - Irritant contact dermatitis is a mayor problem in health care employees. Because
      educational programs have shown convincing success in certain occupations (e.g.
      in hairdressers), this study investigates the effect of a special training
      program in health care trainees. 521 trainees from 14 nursing schools in Central
      Germany were randomly divided in 2 groups, (i) an intervention group with a
      regular teaching protocol regarding all aspects of primary prevention and (ii) a
      control group without any further teaching. Morphological changes of the hands,
      use of hand care creams and knowledge regarding skin care were evaluated
      regularly during their 3 years lasting training period (1999-2002). In the
      intervention group, we found at the end of the 3-year training period a
      significant better skin condition of the hands than in the control group: a 3
      year prevalence of morphological skin changes of 66.7% versus 89.3%. The
      unteached trainees (control group) had an odds ratio (OR) of 4.8 [95%
      confidential interval (CI): 2.9-7.8] for developing any skin changes on the hands
      after 3 years. Besides the effect of the teaching, the history of hand dermatitis
      before the study start was an independent risk factor for development of further
      hand dermatitis [OR 1.9, 95% CI: 1.0-3.6). Age and sex showed no influence on the
      skin condition. Atopic constitution had an influence on the development of skin
      changes only at the evaluation after 18 month. The observed effect in the
      intervention group may best be explained by different behaviour of the trainees,
      e.g. the amount of hand washing was reduced, while procedure of hand disinfection
      remained unchanged compared with the control group. However, the amount of used
      skin care cream did not differ between the both groups. This study shows that
      primary prevention of skin disease by regularly teaching during the training
      period of medical employees can effectively reduce the risk of development of
      irritant skin changes of the hands. Therefore, teaching and continuous motivation
      regarding preventive individual and collective measures during the training of
      medical staff should be an obliged part of the curriculum.

PMID- 16650096
TI  - Rosemary contact dermatitis and cross-reactivity with other labiate plants.
AB  - Rosemary, a plant belonging to the labiate family, is frequently used in the
      making of cosmetics and also for medicinal purposes. There are few reported cases
      of contact dermatitis due to this plant. Here we present 1 case and asses the
      existence of cross-reactivity with plants from the same family. 53-year-old man
      with several episodes of a pruritic and erythematous eruption that resulted in
      peeling of the skin, after applying rosemary alcohol, on the chest reported.
      Epicutaneous tests were done with the standard European series (GEIDC), with the
      commercial plant series (Bial-Aristegui) and with plants from the labiate family.
      Results were positive for 3 of 4 labiate species tested. we present a case of
      rosemary contact dermatitis, where we have found cross-reactivity with 3 of 4
      species tested from the same family.

PMID- 16650097
TI  - Contact dermatitis due to lipsticks and a cream containing isopalmityl diglyceryl
      sebacate (DGS).

PMID- 16650098
TI  - Oral Lichen planus and sensitization to manganese in a dental prosthesis.

PMID- 16650099
TI  - Delayed hypersensitivity following intravenous lidocaine.

PMID- 16650100
TI  - Skin reaction to hydroxyzine (Atarax): patch test utility.

PMID- 16650101
TI  - Contact dermatitis to 2-hydroxyethylamino-5-nitroanisole and 3-nitro-p
      hydroxyethyl aminophenol in a hair dye.

PMID- 16650102
TI  - The influence of contact dermatitis on career change in hairdressers.

PMID- 16650103
TI  - A painful experience: black henna tattoo causing severe, bullous contact
      dermatitis.

PMID- 16650104
TI  - Allergic contact dermatitis from methyl gentisate in a bleaching cream.

PMID- 16650105
TI  - Gold concentration in blood in patients with gold-plated stents.

PMID- 16650106
TI  - Osteosynthesis associated contact dermatitis with unusual perpetuation of
      hyperreactivity in a nickel allergic patient.

PMID- 16650107
TI  - Acute hypersensitivity to dentifrice.

PMID- 16650108
TI  - Allergic contact dermatitis to guggul extract contained in an anticellulite gel
      cream.

PMID- 16650109
TI  - Kiss-induced allergy to amoxycillin.

PMID- 16650110
TI  - Delayed patch positivity to corticosteroids in chronic eczema.

PMID- 16650111
TI  - Dermatitis on the knee following knee replacement: a minority of cases show
      contact allergy to chromate, cobalt or nickel but a causal association is
      unproven.

PMID- 16650112
TI  - Methyldibromoglutaronitrile contact allergy--the beginning of the end?

PMID- 16650113
TI  - IgE-mediated allergy to formaldehyde from topical application.

PMID- 16650114
TI  - Blue dyes in medicine--a confusing terminology.

PMID- 16650115
TI  - Guest editorial: 'Bringing down the Berlin Wall': partnership working and the
      health and social care divide.

PMID- 16650116
TI  - Accessibility and equity of health and social care services: exploring the views
      and experiences of Bangladeshi carers in South Wales, UK.
AB  - There is a paucity of information regarding the extent and nature of caring
      provided by minority ethnic communities. The proportion of older people from
      these communities will dramatically increase in the next 20 years, which will be
      accompanied by increasing health and social care needs and an increased demand
      for carers. A qualitative, exploratory study was conducted to identify the health
      and social care needs of informal carers, who were caring for a dependent adult
      from a Bangladeshi community in South Wales, UK. This paper focuses on
      Bangladeshi carers' access to formal support services provided by the statutory,
      private and voluntary sectors to assist them with their caring responsibilities.
      The findings are based on data collected using face-to-face, focused interviews
      with 20 Bangladeshi carers. Purposive and snowball sampling were used to recruit
      the sample. The data were analysed using thematic content analysis. The
      dimensions of accessibility and equity of quality of care were drawn upon to aid
      understanding of the findings. Bangladeshi carers faced a number of barriers in
      accessing health and social service provision, which impeded uptake of these
      services. Additionally, there was evidence of inequity in service provision.
      Recommendations for improving the accessibility of health and social care
      services are proposed, which may assist in promoting more equitable services for
      carers from the Bangladeshi community.

PMID- 16650117
TI  - Second-tier reviews of complaints in health and social care.
AB  - There has been a flurry of recent government initiatives concerning how citizens
      should be able to take up grievances against the state. In the fields of health
      and social care, people have been expected to use internal complaints procedures
      to resolve grievances. Research in this area suggests that there have been
      problems with the existing complaints procedures and there has been particular
      criticism of the 'second-tier' review stage in both health and social care. This
      has led to the introduction of more independent means of review. Different models
      of review have been developed in England, Wales and Scotland. Based on a review
      of recent policy documents and legislative instruments, this article looks at
      recent changes and proposals and considers the relative merits of the different
      models in the three administrations.

PMID- 16650118
TI  - Expectations of support among White British and Asian-Indian older people in
      Britain: the interdependence of formal and informal spheres.
AB  - Abstract The discourse surrounding community care characterises informal support
      being superior to and preferred over formal sources of support, with this
      distinction buttressed by policy changes. There is a lack of understanding of the
      interdependence of both spheres of support. This article argues that an
      individual's experience and expectation of one type of support is often made in
      relation to his or her understanding, expectation and experience of other sources
      of support. There is also an urgent need to understand how these associations
      operate in a cross-cultural context as it is naive to assume that normative
      expectations will remain constant when the relationship between family, state and
      other sources of support are unstable. This article reports on findings emerging
      from part of a Growing Older study funded by the Economic and Social Research
      Council of Great Britain to explore the relationship between quality of life and
      the social networks and support of older people from different ethnic groups.
      Research involved the use of a questionnaire comprising closed- and open-ended
      questions. In addition, in-depth qualitative interviews covering the existence
      and nature of social networks and support, as well as perceptions and
      expectations of these, were also conducted. This article reports on data relating
      to a sample comprising seven White British men, 10 White British women, 12 Asian
      Indian men, and nine Asian-Indian women aged 55 and over derived from the Family
      Resources Survey. Findings reveal that the high level of expectation for family
      support amongst Asian-Indian respondents coexists with a high level of
      expectation for state support and an acknowledgement that the ideal of family
      support may not always materialise. Amongst White British respondents, the high
      level of expectation for state support exists regardless of whether the
      respondent has satisfactory informal social networks. This expectation is
      commonly expressed in terms of rights and entitlement by White British
      respondents but not by Asian-Indians. Associated with this, Asian-Indian
      respondents display a consistently lower level of awareness and usage of a range
      of health and social care services. Regardless of the extent of current and past
      usage of services, however, respondents from both groups overwhelmingly indicate
      an expectation for the continued provision of such services as they would like to
      be able to use one or more of these at some stage.

PMID- 16650119
TI  - Delayed discharge from mental health hospitals: results of an English postal
      survey.
AB  - This paper reports findings from a postal survey conducted by the UK's NHS
      Confederation to explore the rate and cause of delayed hospital discharges in
      mental health inpatient services. With delayed discharges the subject of
      considerable UK government activity in general hospital settings, there has been
      debate about extending recent financial penalties to mental health, fining social
      services departments for delayed discharges (a system known as reimbursement).
      Against this background, the NHS Confederation sent a postal survey to all 83
      English mental health trusts and Primary Care Trusts with responsibility for
      providing mental health services. This asked respondents about delayed discharges
      from mental health inpatient beds in terms of number of delays, duration of
      delay, specialty and cause. Responses were then analysed quantitatively (in terms
      of number and extent of delays) and qualitatively (attitudes to reimbursement and
      other policies that might help resolve the issue). Overall, the survey reveals
      high levels of delayed discharges (with from 4% to 16% of beds affected and some
      25 to 2,366 bed days lost depending on specialty). The causes of delayed
      discharge are varied, with a range of factors interacting. Although opinion was
      divided on the benefits of extending reimbursement, closer analysis revealed
      greater agreement than may at first be apparent. In particular, those favouring
      extension tended not to be 'pro-reimbursement' per se, but rather desperate to
      tackle delayed discharges and prepared to consider any policy that might help.
      This is an important addition to the current literature and debate, as it
      suggests that those seemingly in favour of reimbursement may actually be more
      motivated by a desire to try anything that might reduce delays rather than by
      commitment to this particular policy.

PMID- 16650120
TI  - Taking the call-bell home: a qualitative evaluation of Tele-HomeCare for
      children.
AB  - Tele-HomeCare (THC) delivers health care at home using telephone technologies. A
      THC service was developed as an adjunct to existing hospital and community care
      systems. It connected healthcare providers to children and families at home,
      during the initial transition from hospital to home, using video-conferencing
      phones and remote vital signs monitors. The goal was to support the transition
      from hospital to home, for children with subacute healthcare needs. This paper
      reports the qualitative evaluation of THC and describes the experiences of
      families supported by THC. A total of 16 mothers, four fathers and two
      adolescents from 16 families participated in a series of interviews conducted
      before, during and after THC. The interviews focused on the impact of THC on the
      children, on the families, and on their overall healthcare experience. Analysis
      of their accounts identified three subthemes: the stable child, a sense of
      security, and the healthcare-proficient parent. These subthemes were consistent
      across all time points and participants. Together they contributed to the overall
      effect of THC: the timely reunification of the family at home. THC was
      consistently reported to be an important resource that supported children and
      families during the transition from hospital to home. The benefits to children
      and families observed in this study may have also been a consequence of returning
      to their home environment, since THC allowed these children to be discharged home
      at a much earlier period. However, our findings are consistent with previous
      reports of the benefits of THC. Thus, THC is a successful method of healthcare
      service delivery that enables a safe return home with professional support
      provided remotely.

PMID- 16650121
TI  - A critical policy analysis of an emerging agenda for home care in one Canadian
      province.
AB  - Amidst projections of the increased care demands and expectations for home care,
      policy in this area demands urgent attention. Home care is inherently complex as
      it challenges us to deliberate fundamental issues of responsibility for care, and
      the limits of care for people in their most immediate contexts and needs. This
      research takes the form of a critical policy analysis of the interaction of the
      context, process and content of policy proposals in home care in a regional
      health system in one Canadian province. The method of study includes thematic and
      comparative analyses of perspectives derived from policy documents, and
      interviews with policy actors (decision-makers, healthcare providers, public
      advocates) regarding their perspectives of policy problems and processes. The
      content and process of policy in home care interact in important ways with
      political, economic, social and historical contexts. This critical analysis
      revealed that the emerging policy agenda in regional home care is one of
      medicalisation, which stands in contrast to the principles of primary health
      care, and potentially leads to further marginalisation of the most vulnerable.
      This contrast is characterised by tensions between the fundamental values of
      equity and efficiency, choice and universality, and public vis-a-vis individual
      responsibility for the provision of care.

PMID- 16650122
TI  - The development of a Local Index of Need (LIN) and its use to explain variations
      in social services expenditure on mental health care in England.
AB  - Wide variations in deprivation exist across England and it is likely that these
      variations translate into differences in the need for mental health care. Social
      Services Departments in England account for a substantial proportion of mental
      health expenditure. It is important that the distribution of expenditure reflects
      mental health needs. This paper's aims are to (1) describe the development of a
      new indicator of mental health needs, (2) use the index to explain variations in
      social services expenditure on mental health, and (3) compare the index with
      other established measures of need. A principal components analysis of
      sociodemographic variables considered to be indicators of need was used to
      produce four distinct factors for 148 Local Authority areas in England. A
      weighted sum of these factors was used to produce a single index. (Weights were
      the proportion of variance explained by each factor.) The index was used in a
      regression model to explain variations in spending on mental health care and was
      compared with (1) a model containing the four individual factors, (2) the current
      method of allocating resources, (3) the index used to allocate resources to
      primary care trusts, (4) the Mental Illness Needs Index (MINI), (5) four indices
      of deprivation produced by the Office of the Deputy Prime Minister, and (6) the
      average of the above four indices. The new index could explain 54% of variation,
      compared with 56% using the current method. The four-factor model could explain
      66%, whilst the other models could explain between 37% and 20%. This new index
      has the advantage that it is not based on previous levels of utilisation or
      expenditure and yet still explains a comparable amount of variation as the
      current method. However, a disaggregated model containing individual factors may
      be preferable.

PMID- 16650123
TI  - Young people living with cystic fibrosis: an insight into their subjective
      experience.
AB  - The aim of this article is to explore the experiences of young people living with
      cystic fibrosis and the impact of these experiences on their compliance to
      treatment regimen. Thirty-one young adults participated in semi-structured
      interviews which were transcribed and the data collected analysed using
      interpretative phenomenology. Emerging themes underlined just how complex it is
      to manage life with a chronic illness as demanding as cystic fibrosis. A strong
      emphasis emerged from the participants about their desire to integrate into
      society and to be seen to be normal and this was seen as in conflict with some
      aspects of their recommended ongoing treatment. The findings suggested that
      complete compliance is rare and is affected by a multitude of factors, set within
      the context of each individual's unique life experience. Healthcare professionals
      need to understand, not just the objective medical condition in delivering care,
      but they also need to develop an insight into the subjective experience of living
      with illnesses such as cystic fibrosis. Their central concern should not be to
      maximise compliance but rather to support the making of informed decisions about
      broader lifestyles and health behaviours.

PMID- 16650132
TI  - Nurse prescribing and the management of epilepsy.

PMID- 16650133
TI  - Inhibition of the multidrug transporter P-glycoprotein improves seizure control
      in phenytoin-treated chronic epileptic rats.
AB  - PURPOSE: Overexpression of multidrug transporters such as P-glycoprotein (P-gp)
      may play a significant role in pharmacoresistance, by preventing antiepileptic
      drugs (AEDs) from reaching their targets in the brain. Until now, many studies
      have described increased P-gp expression in epileptic tissue or have shown that
      several AEDs act as substrates for P-gp. However, definitive proof showing the
      functional involvement of P-gp in pharmacoresistance is still lacking. Here we
      tested whether P-gp contributes to pharmacoresistance to phenytoin (PHT) by using
      a specific P-gp inhibitor in a model of spontaneous seizures in rats. METHODS:
      The effects of PHT on spontaneous seizure activity were investigated in the
      electrical post-status epilepticus rat model for temporal lobe epilepsy, before
      and after administration of tariquidar (TQD), a selective inhibitor of P-gp.
      RESULTS: A 7-day treatment with therapeutic doses of PHT suppressed spontaneous
      seizure activity in rats, but only partially. However, an almost complete control
      of seizures by PHT (93 +/- 7%) was obtained in all rats when PHT was
      coadministered with TQD. This specific P-gp inhibitor was effective in improving
      the anticonvulsive action of PHT during the first 3-4 days of the treatment.
      Western blot analysis confirmed P-gp upregulation in epileptic brains (140-200%
      of control levels), along with approximately 20% reduced PHT brain levels.
      Inhibition of P-gp by TQD significantly increased PHT brain levels in chronic
      epileptic rats. CONCLUSIONS: These findings show that TQD significantly improves
      the anticonvulsive action of PHT, thus establishing a proof-of-concept that the
      administration of AEDs in combination with P-gp inhibitors may be a promising
      therapeutic strategy in pharmacoresistant patients.

PMID- 16650134
TI  - Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and
      serum concentrations of antiepileptic drugs measured intraoperatively in patients
      with intractable epilepsy.
AB  - PURPOSE: The mechanisms of drug resistance in epilepsy are only incompletely
      understood. According to a current concept, overexpression of drug efflux
      transporters at the blood-brain barrier may reduce levels of antiepileptic drugs
      (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux
      transporters such as P-glycoprotein has been found in brain tissue surgically
      resected from patients with medically intractable epilepsy, but it is not known
      whether this leads to decreased extracellular (interstitial) AED concentrations
      in affected brain regions. This prompted us to measure concentrations of AEDs in
      the extracellular space of human neocortical tissue by using intraoperative
      microdialysis (IOMD) in those parts of the brain that had to be removed for
      therapeutic reasons. For comparison, AED levels were determined in brain tissue,
      subarachnoid CSF, and serum. METHODS: Concentrations of carbamazepine (CBZ), 10
      hydroxy-carbazepine (10-OH-CZ, metabolite of oxcarbazepine), lamotrigine (LTG),
      levetiracetam (LEV), topiramate, or phenytoin were determined by using one to
      four catheters during IOMD in the medial temporal gyrus. Furthermore, to
      calculate the individual recovery of every catheter, an in vitro microdialysis
      was performed with ultrafiltrate of serum concurrently obtained from the
      respective patient. In addition, AED levels were determined in the resected brain
      tissue, CSF, and serum of the same patients. Altogether 22 pharmacoresistant
      epilepsy patients (nine male, 13 female patients; age 15-54 years) with complex
      partial seizures or secondarily generalized seizures were involved. In a first
      series, IOMD samples 40 min after beginning of the microdialysis (flow rate, 1
      microl/min), and in a second series, continuous measurements 25, 30, 35, and 40
      min from the beginning were evaluated (flow rate, 2 microl/min). With in vitro
      recovery data of the individual catheters, the concentration in the extracellular
      space (ECS) was estimated. RESULTS: AED concentrations in the ECS of the cortex
      measured by catheters located at a distance of 0.6 cm differed markedly in some
      patients, whereas concentrations in the ultrafiltrate of the serum of the
      respective patients measured with the same catheters varied only slightly.
      Furthermore, ECS concentrations related to the ultrafiltrate of serum showed
      considerable interindividual variations. The high intra- and interindividual
      variation of ECS concentrations is demonstrated by the low correlation between
      concentrations in ECS and the ultrafiltrate of serum (CBZ, r= 0.41; 10-OH-CZ, r=
      0.42; LTG, r= 0.27) in contrast to the high correlation between brain tissue
      concentration and the ultrafiltrate of serum (CBZ, r= 0.97; 10-OH-CZ, r= 0.88;
      LTG, r= 0.98) in the same group of patients. When comparing AED concentrations in
      the ECS with those in the CSF, ECS concentrations were significantly lower for
      CBZ, 10-OH-CZ, LTG, and LEV. CONCLUSIONS: The data demonstrate that AED
      concentrations show a considerable intraindividual and interindividual variation
      in the ECS of cortical regions. Furthermore, the ECS concentration of several
      AEDs is significantly lower than their CSF concentration in patients with
      intractable epilepsy. However, in the absence of data from nonepileptic tissues,
      it is not possible to judge whether the present findings relate to overexpression
      of multidrug transporters in the brain. Instead, the present study illustrates
      the methodologic difficulties involved in performing IOMD studies in patients and
      may thus be helpful for future approaches aimed at elucidating the role of
      multidrug transporters in epilepsy.

PMID- 16650135
TI  - Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate.
AB  - PURPOSE: To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on
      cognitive task-related and resting-state EEG and evoked potential (EP) measures.
      METHODS: We used a double-blind, randomized, crossover design. Healthy adults (N
      = 29) had two 8-week periods of dose escalation, 4 weeks of drug maintenance (300
      mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM)
      tasks and resting conditions at baseline, at the end of each maintenance phase,
      and after final washout. RESULTS. LTG did not affect overt performance on the
      tasks, although it reduced EEG power in both resting and WM task conditions, most
      prominently in the 6- to 12-Hz frequency range, and attenuated P300 evoked
      potential amplitude equally in both WM task loads. TPM slowed responses and
      increased errors. It also increased EEG power below 6 Hz in all conditions, and
      reduced the amplitude of a slow wave observed in a difficult version of the WM
      task. CONCLUSIONS: The drugs produced both task-independent and task-related
      alterations in neurophysiologic measures. The EEG and EP changes produced by TPM
      are consistent with an impairment of WM, as evidenced by overt performance
      deficits on the behavioral tasks. By contrast, the reduction in synchronous
      cortical activity produced by LTG was not accompanied by cognitive impairment. It
      is unknown whether such effects would also be observed at lower doses, such as
      those that often are used in monotherapy for newly diagnosed patients.

PMID- 16650136
TI  - Stiripentol, a putative antiepileptic drug, enhances the duration of opening of
      GABA-A receptor channels.
AB  - PURPOSE: Stiripentol (STP) is currently an efficient drug for add-on therapy in
      infantile epilepsies because it improves the efficacy of antiepileptic drugs
      (AEDs) through its potent inhibition of liver cytochromes P450. In addition, STP
      directly reduces seizures in several animal models of epilepsy, suggesting that
      it might also have anticonvulsive effects of its own. However, its underlying
      mechanisms of action are unknown. METHODS: We examined the interactions of STP
      with gamma-aminobutyric acid (GABA) transmission by using patch-clamp methods in
      CA3 pyramidal neurons in the neonatal rat. RESULTS: STP markedly increased
      miniature inhibitory postsynaptic current (mIPSC) decay-time constant in a
      concentration-dependent manner. The prolongation of mIPSC duration does not
      result from an interaction with GABA transporters because it persisted in the
      presence of GAT-1 inhibitors (SKF-89976A and NO-711). An interaction with
      benzodiazepine or neurosteroid binding sites also was excluded because STP
      mediated increase of decay time was still observed when these sites were
      initially saturated (by clobazam, zolpidem, or pregnanolone) or blocked (by
      flumazenil or dehydroepiandrosterone sulfate), respectively. In contrast,
      saturating barbiturate sites with pentobarbital clearly occluded this effect of
      STP, suggesting that STP and barbiturates interact at the same locus. This was
      directly confirmed by using outside-out patches, because STP increased the
      duration and not the frequency of opening of GABAA channels. CONCLUSIONS: At
      clinically relevant concentrations, STP enhances central GABA transmission
      through a barbiturate-like effect, suggesting that STP should possess an
      antiepileptic effect by itself.

PMID- 16650137
TI  - Retinal nerve fiber layer and macular thickness in adolescents with epilepsy
      treated with valproate and carbamazepine.
AB  - PURPOSE: To evaluate retinal nerve retinal nerve fiber layer (RNFL) and macular
      thickness by using optical coherence tomography (OCT) in epileptic adolescents
      before and during monotherapy with valproic acid (VPA) and carbamazepine (CBZ).
      METHODS: We examined prospectively 45 epilepsy patients with partial and
      generalized epilepsy. The patients were evaluated before the beginning of therapy
      and after 1 year of VPA or CBZ monotherapy. Forty-five untreated healthy controls
      were evaluated at baseline and after 1 year. RESULTS: At the beginning of the
      study, the two groups of patients showed RNFL and macular thickness measurements
      similar to control values. At the end of the follow-up, the data of the three
      groups were similar to baseline, showing no significant differences in the
      evaluated parameters. CONCLUSIONS: The present study demonstrates that no
      modification of RNFL and macular thickness parameters is found after 1 year of
      treatment with VPA and CBZ monotherapy.

PMID- 16650138
TI  - The opening effect of pregabalin on ATP-sensitive potassium channels in
      differentiated hippocampal neuron-derived H19-7 cells.
AB  - PURPOSE: Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels can couple an
      intracellular metabolic state to an electrical activity, which is important in
      the control of neuronal excitability and seizure propagation. We investigated
      whether the newer antiepileptic drug, pregabalin (PGB), could exert effects on
      KATP channels in differentiated hippocampal neuron-derived H19-7 cells. METHODS:
      The inside-out configuration of the patch-clamp technique was used to investigate
      KATP channel activities in H19-7 cells in the presence of PGB. Effects of various
      compounds known to alter KATP channel activities were compared. RESULTS: The
      activity of KATP channels in these cells was characterized. The single-channel
      conductance from a linear current-voltage relation was 78 +/- 2 pS (n = 8) with a
      reversal potential of 63 +/- 2 mV (n = 8), similar to that of KATP channels
      reported in pancreatic beta cells. 2,4-Dinitrophenol activated channel activity,
      but the further addition of glucose (20 mM) or glibenclamide (30 microM) could
      offset these increments. PGB significantly opened these KATP channel activities
      in a concentration-dependent fashion with a median effective concentration (EC50)
      value of 18 microM. A significant increase was noted in the mean open lifetime of
      KATP channels in the presence of PGB (1.71 +/- 0.04 to 5.62 +/- 0.04 ms).
      CONCLUSIONS: This study suggests that in differentiated hippocampal neuron
      derived H19-7 cells, the opening effect on KATP channels could be one of the
      underlying mechanisms of PGB in the reduction of neuronal excitability.

PMID- 16650139
TI  - Effects of potassium concentration on firing patterns of low-calcium epileptiform
      activity in anesthetized rat hippocampus: inducing of persistent spike activity.
AB  - PURPOSE: It has been shown that a low-calcium high-potassium solution can
      generate ictal-like epileptiform activity in vitro and in vivo. Moreover, during
      status epileptiform activity, the concentration of [K+]o increases, and the
      concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the
      hypothesis that long-lasting persistent spike activity, similar to one of the
      patterns of status epilepticus, could be generated by a high-potassium, low
      calcium solution in the hippocampus in vivo. METHODS: Artificial cerebrospinal
      fluid was perfused over the surface of the exposed left dorsal hippocampus of
      anesthetized rats. A stimulating electrode and a recording probe were placed in
      the CA1 region. RESULTS: By elevating K+ concentration from 6 to 12 mM in the
      perfusate solution, the typical firing pattern of low-calcium ictal bursts was
      transformed into persistent spike activity in the CA1 region with synaptic
      transmission being suppressed by calcium chelator EGTA. The activity was
      characterized by double spikes repeated at a frequency approximately 4 Hz that
      could last for >1 h. The analysis of multiple unit activity showed that both
      elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the
      response of paired-pulse stimulation, indicating a suppression of the after
      hyperpolarization (AHP) activity. CONCLUSIONS: These results suggest that
      persistent status epilepticus-like spike activity can be induced by nonsynaptic
      mechanisms when synaptic transmission is blocked. The unique double-spike pattern
      of this activity is presumably caused by higher K+ concentration augmenting the
      frequency of typical low-calcium nonsynaptic burst activity.

PMID- 16650140
TI  - The ictal bradycardia syndrome: localization and lateralization.
AB  - PURPOSE: Previous studies have established the importance of the insular cortex
      and temporal lobe in cardiovascular autonomic modulation. Some investigators,
      based on the results of cortical stimulation response, functional imaging, EEG
      recordings of seizures, and lesional studies, have suggested that cardiac
      sympathetic and parasympathetic function may be lateralized, with sympathetic
      representation lateralized to the right insula, and parasympathetic, to the left.
      These studies have suggested that ictal bradycardia is most commonly a
      manifestation of activation of the left temporal and insular cortex. However, the
      evidence for this is inconsistent. We sought to assess critically the predictable
      value of ictal bradycardia for seizure localization and lateralization. METHODS:
      In this study, we reviewed the localization of seizure activity in 13 consecutive
      patients with ictal bradycardia diagnosed during prolonged video-EEG monitoring
      at Mayo Clinic Rochester. The localization of electrographic seizure activity at
      seizure onset and bradycardia onset was identified in all patients. In addition,
      we performed a comprehensive review of the ictal bradycardia literature focusing
      on localization of seizure activity in ictal bradycardia cases. RESULTS: All
      occurrences of ictal bradycardia in the 13 identified patients were associated
      with temporal lobe-onset seizures. However, no consistent lateralization of
      seizure activity was found at onset of seizure activity or at onset of
      bradycardia in this population. Seizure activity was bilateral at bradycardia
      onset in nine of 13 patients. The results from the literature review also showed
      that a predominance of patients had bilateral activity at bradycardia onset;
      however, more of the ictal bradycardia cases from the literature had left
      hemispheric localization of seizure onset. CONCLUSIONS: Ictal bradycardia most
      often occurs in association with bilateral hemispheric seizure activity and is
      not a consistent lateralizing sign in localizing seizure onset. Our data do not
      support the existence of a strictly unilateral parasympathetic cardiomotor
      representation in the left hemisphere, as has been suggested.

PMID- 16650141
TI  - Imaging the neural substrates involved in the genesis of pentylenetetrazol
      induced seizures.
AB  - PURPOSE: Functional imaging of animal models makes it possible to map the
      functional neuroanatomy contributing to the genesis of seizures.
      Pentylenetetrazol (PTZ)-induced seizure in rats, a relevant model of human
      absence and of generalized tonic-clonic epilepsy, was used to stimulate seizure
      activity within 30 s of administration while collecting continuous, high
      resolution, multislice images at subsecond intervals. METHODS: Pilot studies were
      conducted to establish a quick and effective PTZ model for the imaging
      experiments. PTZ was then used to stimulate seizure activity in rats while
      collecting multislice functional MRI (fMRI) images from the entire forebrain at
      4.7 Tesla. Ethosuximide (ESM) also was used to block seizure activity. RESULTS:
      Within 2-4 s of PTZ administration, a rapid increase in blood oxygen level
      dependent (BOLD) signal intensity was noted in the thalamus, especially the
      anterior thalamic nuclei. Activity in the anterior thalamus peaked approximately
      15 s before seizure onset and was more than twofold greater than that in all
      other thalamic areas. The retrosplenial cortex showed a twofold greater increase
      in activity as compared with other cortical areas, also peaking at approximately
      15 s. The dentate gyrus was twice as active as other hippocampal areas but peaked
      just before seizure onset. Treatment with ESM blocked seizures, decreasing PTZ
      induced activation in most forebrain areas. The anterior thalamus and
      retrosplenial cortex were essentially blocked by pretreatment with ESM.
      CONCLUSIONS: The anterior thalamus, retrosplenial cortex, and dentate gyrus show
      the greatest increases in BOLD signal activity before seizure onset. Neurons in
      these areas may contribute to the neural network controlling the initiation of
      generalized tonic-clonic seizure.

PMID- 16650142
TI  - Nocturnal hypermotor seizures, suggesting frontal lobe epilepsy, can originate in
      the insula.
AB  - PURPOSE: To report three patients with drug-resistant nocturnal hypermotor
      seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal
      frontal lobe epilepsy (NFLE) or autosomal dominant NLFE (ADNFLE), whose
      intracerebral EEG ictal onset primarily involved the insula, rather than the
      mesial or orbital frontal cortex. METHODS: Fourteen to 15 intracerebral
      electrodes were implanted in each patient, primarily sampling the frontal lobes
      with 80 to 91 recording leads covering the most likely side of seizure onset, and
      two to six leads placed within the ipsilateral insula. Electrical stimulation was
      used to test the epileptic threshold of frontal and insular brain regions at the
      various recording sites. RESULTS: In all three patients, a low-voltage fast
      activity was recorded within the anterosuperior aspect of the insula at ictal
      onset, either in isolation, or extending to the nearby frontal operculum in the
      ADNFLE patient. The role of the insula was further supported in all three
      patients either by the presence of high-amplitude spikes that clearly
      predominated over that region (n = 2) or by triggering the patient's typical aura
      or seizure when applying an electrical stimulation at that site, selectively (n =
      2). CONCLUSIONS: The anterosuperior portion of the insula might play a pivotal
      role in generating nocturnal hypermotor seizures in some patients with
      nonlesional drug-resistant epilepsy suggesting NFLE or ADNFLE. Whether these
      patients are amenable to successful surgery remain an open issue.

PMID- 16650143
TI  - Language-induced epilepsy, acquired stuttering, and idiopathic generalized
      epilepsy: phenotypic study of one family.
AB  - PURPOSE: Language-induced epilepsy involves seizure precipitation by speaking,
      reading, and writing. Seizures are similar to those of reading epilepsy (RE). The
      nosologic position of language-induced epilepsy is not clear. We performed a
      clinical and neurophysiological study in a multigenerational family with the
      association of idiopathic generalized epilepsy (IGE) with ictal stuttering as a
      manifestation of reflex language-induced epilepsy. METHODS: Nine members on three
      generations were studied. All patients underwent video-polygraphic EEG recordings
      (awake and during sleep). A standardized protocol was applied to test the effect
      of language and non-language-related tasks. RESULTS: Six patients presented
      language-induced jaw jerking that mimicked stuttering and corresponded to focal
      myoclonus involving facial muscles. This was associated with an IGE phenotype in
      four of these patients. Focal EEG spikes were found in all six patients by visual
      analysis and/or back-averaging techniques. The focal spikes were either
      asymptomatic (when followed by a slow wave) or symptomatic of facial myoclonia
      (when isolated). Levetiracetam, used as add-on or monotherapy in four patients,
      suppressed ictal stuttering. One additional case only had a phenotype of IGE
      without focal features. CONCLUSIONS: This family study demonstrates the
      phenotypic heterogeneity of the association of IGE phenotype with ictal
      stuttering (language-related reflex seizure). Our data suggest that this
      particular form of reflex epilepsy related to language has more similarities with
      generalized epilepsies than with focal ones. Neurophysiological investigations
      should be performed more systematically in patients with acquired stuttering,
      especially if there is family history of IGE.

PMID- 16650144
TI  - Differential actions of NPY on seizure modulation via Y1 and Y2 receptors:
      evidence from receptor knockout mice.
AB  - PURPOSE: Neuropeptide Y (NPY) has been shown to modulate seizure activities. To
      provide further understanding of the involvement of two of the most abundantly
      expressed NPY receptors, Y1 and Y2, we assessed the effect of Y1 and Y2 gene
      deletion on systemic kainic acid-induced seizures. We also examined the effect of
      rAAV-mediated hippocampal NPY overexpression on seizure susceptibility in these
      receptor knockout mice. METHODS: Recombinant adeno-associated viral vector
      overexpressing NPY (rAAV-NPY) or an empty vector control (rAAV-Empty) was
      injected into the hippocampus of adult C57BL/6-129/SvJ wild-type male mice and
      mice deficient of Y1 or Y2 receptors on the same background. Four weeks after
      vector injection, mice were subjected to systemic kainic acid-induced seizures,
      and the seizure behaviors were scored. RESULTS: The rAAV-mediated hippocampal
      overexpression of NPY led to a twofold reduction in seizures induced by systemic
      kainic acid in wild-type mice and Y1 receptor knockout mice but not in mice
      deficient of Y2 receptors. A differential action by the receptors was observed in
      the seizure-induced mortality rate, with increased fatality in Y2-/- mice. In
      addition, although NPY overexpression did not significantly affect the mortality
      rate in Y2-/- and wild-type mice, it abolished KA-induced mortality in Y1-/-mice.
      CONCLUSIONS: This study shows for the first time an altered susceptibility to
      chemically induced seizures in Y1 and Y2 knockout mice and demonstrates a
      differential seizure modulation mediated by these receptors via a genetic
      approach.

PMID- 16650145
TI  - EEG dipole characteristics in Panayiotopoulos syndrome.
AB  - PURPOSE: Panayiotopoulos syndrome (PS) is a type of benign childhood partial
      epilepsy that is frequently associated with abundant multifocal spikes other than
      main occipital spikes on the EEG. In this study, we investigated the
      characteristic features of dipoles in PS. METHODS: We performed dipole analysis
      of the interictal occipital spike discharges seen in 10 children with PS (group
      A) and in 10 children with other types of symptomatic localization-related
      epilepsy (group B). We analyzed the dipoles of the averaged spike in each
      patient. RESULTS: In group A, the averaged occipital spikes in each patient
      showed dense dipole locations in the mesial occipital area; in group B, widely
      scattered dipole locations were observed. In Group A, the geometric centers of
      the dipoles at each time point (such as at the main negative peak and before or
      after the main peak) were estimated in the neighboring locations. In contrast,
      they tended to be scattered in group B. CONCLUSIONS: Our study reveals that PS
      has high dipole stability, similar to that of rolandic epilepsy. From the
      electroencephalographic view, this seems to indicate a close link between these
      two syndromes.

PMID- 16650146
TI  - MRI volumetry and proton MR spectroscopy of the brain in Lafora disease.
AB  - PURPOSE: To determine brain involvement in Lafora disease by means of 3-T MRI
      volumetry and 1H magnetic resonance (MR) spectroscopy. METHODS: Ten patients with
      Lafora disease and 10 healthy controls were included in the study. The diagnosis
      of Lafora disease was proven genetically by the presence of mutations in the
      EPM2A gene in all patients, and their evolution was staged in three groups
      according to their functional state. MRI volumetry was performed by means of
      AX3DT1 images with assessment of the cerebellum and the brainstem, by using the
      program Stereonauta, and all the brain structures, by using voxel-based
      morphometry. [1H]MR spectroscopy was performed by using an Eclipse PRESS sequence
      probe system with 8-cc voxels positioned in the occipital and frontal cortexes,
      basal ganglia, pons, and cerebellar hemispheres. Spectral peak areas
      corresponding to NAA (N-acetylaspartate), creatine, and choline were obtained.
      RESULTS: MRI volumetry showed no statistically significant differences in
      patients compared with healthy controls in any of the analyzed structures.
      Analysis of [1H]MR spectroscopy data showed a statistically significant reduction
      in the NAA/creatine ratio in patients compared with controls in the frontal (p =
      0.001) and occipital cortex (p = 0.043), basal ganglia (p = 0.002), and
      cerebellar hemispheres (p = 0.007). The NAA/choline and choline/creatine ratios
      were statistically significantly different in the frontal cortex (p = 0.005). No
      correlation was observed between the disease-evolution stage and MRI-measured
      volumes (range, -0.92 to 0.44) or [1H]MR spectroscopy values (range, -0.29 to
      0.50). CONCLUSIONS: In our series of Lafora disease patients, [1H]MR spectroscopy
      was more sensitive than structural MRI to detect brain involvement. The brain
      cortex, especially frontal cortex, cerebellum, and basal ganglia, showed the
      greatest metabolic changes.

PMID- 16650147
TI  - Epileptic seizures superimposed on catatonic stupor.
AB  - PURPOSE: Some patients with nonconvulsive status epilepticus are known to exhibit
      catatonic stupor. Thus it is necessary to rule out ictal catatonia by
      electroencephalography in patients with catatonic stupor. However, few reports
      are available on epileptic seizures superimposed on catatonic stupor. METHODS: We
      report three cases of epileptic seizures superimposed on psychiatric catatonic
      stupor without a prominent predisposing factor, including high fever or
      encephalitis. None of the patients had a personal or family history of neurologic
      disease, including epilepsy. RESULTS: In all three patients, catatonic stupor
      persisted after resolution of the epileptic seizures with administration of
      phenytoin. In two of the three patients, catatonic stupor resolved with
      electroconvulsive therapy, which caused no marked adverse effects. CONCLUSIONS:
      Because it is possible that catatonic stupor itself predisposes patients to the
      development of epileptic seizures, electroencephalographic examinations in
      patients with catatonic stupor are indispensable for early recognition not only
      of nonconvulsive status epilepticus but also of epileptic seizures superimposed
      on catatonic stupor. Electroconvulsive therapy deserves consideration when
      catatonic stupor persists after resolution of epileptic seizures.

PMID- 16650148
TI  - Transient athetosis induced by tiagabine.
AB  - Movement disorders have been reported with use of different antiepileptic drugs
      (AEDs). We report a 32-year-old woman, affected by a symptomatic focal drug
      resistant epilepsy and a mild hemiparesis, with acute athetoid movements,
      transiently linked to increasing tiagabine (TGB) therapy. To our knowledge, no
      other cases of acute athetosis related to TGB have been reported to date.
      However, we cannot rule out the possibility that involuntary movements were
      induced by an interaction between TGB and concomitant AEDs, in particular
      phenobarbital (PB), possibly by increasing GABAergic transmission. We hypothesize
      that the presence of a static encephalopathy may have influenced the kind of
      extrapyramidal side effect induced by TGB in our patient, leading to athetosis.

PMID- 16650149
TI  - Routine tail suspension husbandry facilitates onset of seizure susceptibility in
      EL mice.
AB  - PURPOSE: Tail suspension can elicit seizures in susceptible EL mice, a model of
      idiopathic, multifactorial epilepsy. Further, repeated tail suspension hastens
      the lifetime onset of seizure susceptibility in these mice. The present study
      tested the hypothesis that curtailing human handling during development would
      delay the onset of seizure susceptibility relative to EL mice handled regularly
      by using tail suspension for standard laboratory husbandry. METHODS: Control mice
      were handled by the tail for bedding changes, whereas unhandled mice bedding was
      changed by using specially designed connector cages that allowed mice to transfer
      without handling to a cage containing clean bedding. Seizure susceptibility was
      tested beginning at 70, 80, 90, 100, or 140 days of age by using a handling
      induced seizure-susceptibility paradigm. RESULTS: Among handled mice, more than
      half of the sample exhibited seizures by age 80 days relative to fewer than one
      fourth of unhandled mice. In addition, each group was tested a second time 10
      days after the initial seizure-susceptibility test to detect potential experience
      induced increases in seizure susceptibility. Once again, a higher frequency of
      handled mice expressed seizures at significantly younger ages relative to
      unhandled mice. CONCLUSIONS: Although it was already known that repeated tail
      suspension could speed the onset of seizure susceptibility in EL mice, the
      present results are the first to demonstrate the converse finding that decreasing
      routine human handling can delay significantly the onset of seizure
      susceptibility. This suggests that removal of nonconsensual aspects of human
      animal contact may delay or prevent the onset of seizure susceptibility.

PMID- 16650150
TI  - Status epilepticus in idiopathic generalized epilepsy.

PMID- 16650151
TI  - Similarity of balloon cells in focal cortical dysplasia to giant cells in
      tuberous sclerosis.

PMID- 16650152
TI  - "Migralepsy" and the significance of differentiating occipital seizures from
      migraine.

PMID- 16650154
TI  - alpha-Difluoromethylornithine, a polyamine inhibitor: its potential role in
      controlling hair growth and in cancer treatment and chemo-prevention.

PMID- 16650155
TI  - Treatment of basal cell carcinomas by general practitioners in Australia.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) are a relatively common form of skin
      damage in Australians, involving approximately 1 in 200 general practice
      encounters per year. AIM: To determine current treatments and the associated
      healthcare resource costs of BCC therapy in Australia. METHODS: A retrospective
      survey was undertaken relating to the treatment of patients presenting to their
      doctor with previously untreated BCCs. Data were collected from a sample of
      general practitioners who were asked to randomly select two BCC patients from
      their medical records and complete a questionnaire. Information about treatment
      types, number of doctor visits, treatment complications, and specialist referrals
      was extracted from the patient records. RESULTS: One hundred and sixty-four
      patients were recruited into the study (59% male), who were treated for a total
      of 244 BCCs (average of 1.5 lesions per patient). Twenty-two per cent of patients
      were referred to a specialist, most being referred to a general surgeon (45%) or
      plastic surgeon (25%). Excision was the preferred therapy; second choices were
      cryosurgery or curettage and cautery. Few adverse events were recorded. The
      typical number of doctor visits varied from 3.2 to 7.4, with a range of total
      cost per patient of 146.60-496.20 AUS dollars, depending on complexity and the
      need for referral. CONCLUSION: With a reported incidence in Australia of
      approximately 788 per 100,000 persons, BCCs are not inexpensive to treat for such
      a relatively common condition.

PMID- 16650156
TI  - A study to determine the effect of tacrolimus on ceramide levels in the stratum
      corneum of patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is characterized both by inflammation and by
      abnormally low ceramide levels in the stratum corneum. Tacrolimus, effective in
      the treatment of AD, inhibits transcription and release of inflammatory cytokines
      operative in AD, but it is unknown if tacrolimus normalizes ceramide levels.
      METHODS: Stratum corneum ceramides of seven subjects with lesional AD were
      measured before and after treatment with tacrolimus ointment. RESULTS: Treatment
      with tacrolimus ointment did not increase the ceramide fractions toward or to
      normal. CONCLUSION: These findings suggest that tacrolimus ointment is effective
      in the treatment of atopic dermatitis due to its anti-inflammatory actions rather
      than to any restorative effect on stratum corneum ceramides.

PMID- 16650157
TI  - The Azerbaijani scrub: a simple method to harvest large amounts of stratum
      corneum.
AB  - BACKGROUND: The study of skin barrier constituents may require collection of much
      stratum corneum. Existing methods are inadequate and/or difficult. METHODS: A
      simple and safe method to harvest stratum corneum from glabrous human skin
      derives from the bathing practices of people in Azerbaijan. The method requires
      water immersion of the subject for 30 min immediately followed by vigorous
      scrubbing of skin with a moist rough crepe mitten. RESULTS: This scrubbing method
      causes the separation of large amounts of stratum corneum which is easily
      harvested. CONCLUSION: The method facilitates study of stratum corneum
      components, including intercellular lipids.

PMID- 16650158
TI  - Porokeratosis of Mibelli following bone marrow transplantation.
AB  - BACKGROUND: Porokeratosis is a rare disorder of keratinization with both
      autosomal dominant and acquired forms. Immunosuppression has been associated with
      the development of porokeratosis in numerous case reports and series. To our
      knowledge, however, only five cases of porokeratosis have been reported following
      bone marrow transplantation. RESULTS: We report five cases of porokeratosis of
      Mibelli following bone marrow transplantation. The diagnosis of porokeratosis was
      made between 1 and 13 years post-transplantation. The underlying malignancy in
      four of the five cases was leukemia, while the fifth patient had non-Hodgkin's
      lymphoma. Porokeratosis developed during remission in the four leukemia patients,
      whereas, in the fifth patient, it occurred during a relapse of lymphoma.
      CONCLUSIONS: Porokeratosis may develop following bone marrow transplantation. Our
      five cases double the number reported in the medical literature, and the
      incidence of porokeratosis following bone marrow transplantation may be
      significantly higher than previously recognized. As cutaneous carcinomas have
      been reported in association with porokeratosis, careful surveillance for
      porokeratosis in bone marrow transplant recipients is warranted.

PMID- 16650159
TI  - Borderline systemic lupus erythematosus (SLE): a separate entity or a forerunner
      to SLE?
AB  - AIM: To compare a subgroup of patients with borderline systemic lupus
      erythematosus (SLE) with those with classic lupus in order to determine whether
      the former subset is a separate entity or a forerunner to SLE. METHODS: A
      retrospective survey was undertaken of a database containing the clinical
      information of a total of 71 patients in an Abu Dhabi hospital setting over a 12
      year period. Data of interest were criterial and non-criterial features of SLE
      together with relevant laboratory tests. RESULTS: Fifty-six patients had SLE and
      15 were considered to have borderline SLE as they satisfied less than four
      criteria of classification. Age and female sex distribution were no different in
      the two subgroups, but the disease duration was shorter in patients with
      borderline lupus. The occurrence of arthropathy (non-erosive), serositis,
      thrombocytopenia, hemolytic anemia, and malar eruption was common to both
      subgroups. Patients with borderline SLE lacked other mucocutaneous manifestations
      of lupus and major organ disease involvement. A number of other clinical features
      were also observed in the latter subgroup, including antiphospholipid (APL)
      syndrome. In addition, patients with borderline SLE expressed a multiple
      autoantibody profile, but had lower titers of antinuclear factor (ANF) and anti
      double-stranded DNA (anti-dsDNA) antibodies than those with classic SLE. None
      progressed to full-blown SLE after a mean period of follow-up of 21.2 months.
      CONCLUSIONS: In our patients, borderline SLE was milder than classic lupus, yet
      shared a wide spectrum of non-criterial features and also produced clinical
      subsets. The clinical heterogeneity and multiple antibody profile may suggest
      that borderline SLE is a forerunner to SLE rather than a separate entity. A
      regular and longer period of follow-up is required, however, to ultimately
      determine the fate of these patients.

PMID- 16650160
TI  - Psoriasis treatment in the United States at the end of the 20th century.
AB  - BACKGROUND: Psoriasis presents many management complexities. A cornerstone of
      therapy has been topical corticosteroids, although over the past 10 years there
      have been many additions to the medication armamentarium. Furthermore, various
      combination regimens and approaches have been advocated. OBJECTIVE: We sought to
      characterize various patterns of psoriasis health care delivery and the changes
      associated with these patterns from 1990 to 2001. METHODS: Visits for psoriasis
      were identified using National Ambulatory Medical Care survey data, a
      representative survey of visits to physician offices in the United States. We
      determined basic demographic characteristics, specialty of the physician provider
      and medications listed at these visits over the 1990-2001 interval. RESULTS:
      There were more than 13.5 million visits for psoriasis during the 12-year study
      period. Dermatologists were responsible for the majority of the visits over the
      study interval (82%) although there was an overall decline in the proportion of
      psoriasis visits to dermatologists. As a category, the most common medications
      used for psoriasis were topical steroids. Topical calcipotriene was the single
      most listed medication. There was no observed use of non-corticosteroid topical
      agents at visits to non-dermatologists. Non-dermatologists were as likely as
      dermatologists to list a systemic medication at a visit as well as use a systemic
      as monotherapy. DISCUSSION: In conclusion, the primary topical therapies for
      psoriasis remain clobetasol and calcipotriene. The decreasing role of
      dermatologists in the treatment of psoriasis is probably a complex issue, but may
      relate in part to the difficulty of obtaining access to dermatology care.

PMID- 16650161
TI  - Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological
      study.
AB  - BACKGROUND: Frontal fibrosing alopecia (FFA) is an acquired scarring alopecia
      currently considered a clinical variant of lichen planopilaris (LPP). Our purpose
      was to examine the clinicopathological features of FFA. In addition, we
      investigated the similarities and differences between FFA and LPP. METHODS:
      Biopsies from the scalp lesions of eight patients with FFA and eight patients
      with LPP were microscopically analyzed. Two cases of FFA and four cases of LPP
      were studied using direct immunofluorescence. RESULTS: In spite of the completely
      different clinical characteristics of FFA and LPP patients, the histopathological
      findings for the two entities were similar. Common microscopic findings for both
      FFA and LPP included an inflammatory lymphocytic infiltrate involving the isthmus
      and infundibulum of the hair follicles, the presence of apoptotic cells in the
      external root sheath, and a concentric fibrosis surrounding the hair follicles
      that resulted in their destruction with subsequent scarring alopecia. Biopsies
      taken from FFA patients showed less follicular inflammation and more apoptotic
      cells than those from LPP patients. In some cases of LPP, the inflammatory
      infiltrate involved the interfollicular epidermis, a finding never present in our
      FFA cases. Direct immunofluorescence was negative in the two cases of FFA studied
      and showed deposits of immunoglobulins and/or complement in two of the four LPP
      cases examined. CONCLUSIONS: The characteristic findings for FFA were more
      prominent apoptosis and less inflammation than found in LPP, along with spared
      interfollicular epidermis. FFA cases showed a rather characteristic
      histopathological pattern, although we could not find any clear-cut histological
      differences between FFA and LPP.

PMID- 16650162
TI  - Seroprevalence of HHV-8 infection in the pediatric population of two university
      hospitals in Rio de Janeiro, Brazil.
AB  - BACKGROUND: The authors present a serologic survey of the prevalence of
      herpesvirus-8 (HHV-8) among 171 children from 0 to 12 years old in Rio de
      Janeiro, Brazil. MATERIALS AND METHODS: Sera were tested for latent nuclear and
      lytic antigens using indirect immunofluorescence and Western blotting. RESULTS:
      Serology for HHV-8 was positive in 16 of 171 patients (9.35%). Among 13 HIV
      positive patients, four (31%) were also positive for HHV-8. The seropositivity
      among healthy children was 7.6%, and females were significantly (P<0.002) more
      associated with HHV-8 seropositivity (16%) than males (1.1%). CONCLUSIONS: We
      detected a higher HHV-8 seroprevalence among the pediatric population in Rio de
      Janeiro, Brazil, when compared with similar studies performed in other countries.
      Nonsexual routes of transmission are a possible explanation for this pattern. The
      unusual finding of a higher seroprevalence among female children could be
      explained by a specific route of exposition or even an epidemiological bias.

PMID- 16650163
TI  - Skin cancer trends in northern Jordan.
AB  - BACKGROUND: The Jordan Cancer Registry was established in 1996, since which time
      all cases of cancer have been reported and registered. We have used this registry
      to perform the first analysis of skin cancer in northern Jordan and to compare
      our findings with those of published reports from other regions. METHODS: All
      histopathologically proven cases of skin cancer, reported during the years 1997
      through 2001, were reviewed. Information regarding tumor type, age, gender, and
      anatomical location was collected. RESULTS: A total of 272 cases of malignant
      skin tumors were diagnosed between the years 1997 and 2001. Basal cell carcinoma
      (BCC) was the commonest type, representing 52.9% of all skin cancers. Females
      were more frequently affected than males, with age-adjusted incidence rates of
      23.3 and 19.7 per 100,000 of population, respectively. Squamous cell carcinoma
      (SCC) comprised 26.4% of the total, its age-adjusted incidence rate per 100,000
      of population being 14.2 for males and 6.18 for females. the incidence rate
      increased in males and decreased in females during the study period. The
      incidence of both BCC and SCC increased with age. The head and neck region was
      the commonest site affected by both types of cancer. Malignant melanoma (MM)
      comprised 11.39% of all skin cancer cases, with a female to male ratio of 1.2 :
      1. The median age at onset for female patients was 49 years while that for males
      was 70 years, and the commonest site affected was the lower limbs, followed by
      the trunk. CONCLUSIONS: In Jordan, sun-related skin cancers have relatively low
      incidences and a rather stable pattern, compared with other areas with similar
      climate and skin phenotypes.

PMID- 16650164
TI  - Acropustulosis repens.
AB  - BACKGROUND: Pustular eruptions of the extremities of the fingers and toes
      (acropustulosis) have been grouped under the single term "Hallopeau's
      acrodermatitis continua", which is a severe disease, with uninterrupted course,
      and successive eruptions that may become generalized. However, there is a form of
      acropustulosis with few lesions, evolving with remissions and relapses, with a
      benign course. It is necessary to separate these two forms of acropustulosis.
      METHODS: I had the opportunity to observe six patients with a mitigated form of
      acropustulosis that does not fit into the diagnostic criteria of Hallopeau's
      acrodermatitis continua, which should be considered an independent clinical
      entity. RESULTS: Sometimes, there is only one lesion in each eruption. The
      pustules are sterile and appear in small crops, located on the hyponychium or on
      the nail bed. The result is partial onycholysis or nail detachment. After each
      eruption there is complete recovery. Histopathology shows a nonspongiform pustule
      filled with neutrophils, with subcorneal localization. Four patients had follow
      up for at least 2 years, and one patient presented psoriasis lesions on the scalp
      after 11 years. CONCLUSIONS: Acropustulosis as I described it can be
      differentiated from Halopeau's acrodermatitis continua using the following
      diagnostic criteria: (1) it is a benign condition; (2) the pustules are located
      on the hyponychium or nail bed; (3) pustules can be single or occur in small
      groups; (4) they reccur in flares, with restitutio ad integrum during the periods
      of remission; (5) the pustules are sterile; (6) microscopic study shows a
      subcorneal pustule (spongiform aspect is rare). A similar condition to that found
      in my cases was described by Radcliff-Crocker (H. Radcliff-Crocker, Diseases of
      the Skin, London: H.K. Lewis, 1888), termed "dermatitis repens".

PMID- 16650165
TI  - Influence of desloratadine on oxidative stress markers in patients with chronic
      idiopathic urticaria.
AB  - BACKGROUND: Recent findings suggest the involvement of oxidative stress in the
      pathogenesis of chronic idiopathic urticaria (CIU). It has been demonstrated that
      desloratadine has an antioxidant activity in vitro. We evaluated the effects of
      desloratadine on markers of oxidative stress in patients with CIU. METHODS: Blood
      samples were obtained from 10 patients with CIU before and after 4 weeks of
      treatment with desloratadine. Blood samples from 10 healthy volunteers were used
      as controls. In platelets from both patients and controls, radical oxygen species
      (ROS) production was measured using spectrofluorimetric detection of dichloro
      fluorescein oxidation, and superoxide dismutase (SOD) activity was determined by
      means of the xanthine-xanthine oxidase system. RESULTS: Radical oxygen species
      concentrations and SOD activity were significantly elevated in patients with CIU
      at baseline as compared with control subjects. Treatment with desloratadine
      caused a relevant reduction of ROS levels and SOD activity (P<0.005).
      CONCLUSIONS: These preliminary results suggest that desloratadine exerts
      antioxidant effects also in vivo.

PMID- 16650166
TI  - The incidence of cutaneous melanoma on Crete, Greece.
AB  - BACKGROUND: For Greece, no data regarding the incidence of cutaneous melanoma
      (CM) have been reported. In this report, we present epidemiologic data for CM on
      Crete, an island in southern Greece, during the years 1999-2002. We attempt a
      comparison with corresponding data reported for the Italian population. METHODS:
      One hundred and two CM patients of Cretan origin with primary CM first diagnosed
      between the years 1999-2002 were interviewed and underwent complete skin
      examination by the same two experienced dermatologists. Crude and/or age
      standardized incidence rates were calculated for Crete as a whole, as well as for
      each one of the four prefectures of the island. RESULTS: The age-standardized
      incidence rate according to the Greek population was 4.6 per 100,000 person-years
      for men and 4.7 per 100,000 person-years for women. The crude incidence rates did
      not differ significantly between the four prefectures. Significant differences
      between Cretan and Italian CM patients were found in terms of gender, age at
      diagnosis, anatomic site and histogenetic type of CM, hair color, skin reaction
      to sun exposure, history of sunburn before the age of 15 years, presence of solar
      lentigines, and total common nevus count. CONCLUSIONS: The incidence of CM on
      Crete is higher than that estimated for the whole of Greece and comparable with
      the incidence reported for other southern European countries.

PMID- 16650167
TI  - A simple digital image processing system to aid in melanoma diagnosis in an
      everyday melanocytic skin lesion unit: a preliminary report.
AB  - BACKGROUND: For early melanoma diagnosis, experienced dermatologists have an
      accuracy of 64-80% using clinical diagnostic criteria, usually the ABCD rule,
      while automated melanoma diagnosis systems are still considered to be
      experimental and serve as adjuncts to the naked-eye expert prediction. In an
      attempt to aid in early melanoma diagnosis, we developed an image processing
      program with the aim to discriminate melanoma from melanocytic nevi, establishing
      a mathematical model to come up with a melanoma probability. METHODS: Digital
      images of 132 melanocytic skin lesions (23 melanomas and 109 melanocytic nevi)
      were studied in features of geometry, color, and color texture. A total of 43
      variables were studied for all lesions, e.g., geometry, color texture, sharpness
      of border, and color variables. Univariate logistic regression analysis followed
      by "-2 log likelihood" test and Spearman's rank correlation coefficient were used
      to eliminate inappropriate variables, as the presence of multi-collinearity among
      variables could cause severe problems in any stepwise variable selection method.
      Initially, "-2 log likelihood" and nonparametric Spearman's rho picked five
      variables to be included in a multivariate model of prediction. The five-variable
      model was then reduced to three variables and the performance of each model was
      tested. The "jackknife" method was performed in order to validate the model with
      the three variables and its accuracy was weighed vs. the five-variable model by
      receiver-operating characteristics (ROC) curve plotting. It was concluded that
      the reduced model did not compromise discriminatory power. RESULTS: Not all
      variables contributed much to the model, therefore they were progressively
      eliminated and the model was finally reduced to three covariates of significance.
      A predictive equation was calculated, incorporating parameters of geometry,
      color, and color texture as independent covariates for the prediction of
      melanoma. The proposed model provides melanoma probability with a 60.9%
      sensitivity and 95.4% specificity of prediction, an overall accuracy of 89.4%
      (probability level 0.5), and 8% false-negative results. CONCLUSIONS: Through a
      digital image processing system and the development of a mathematical model of
      prediction, discrimination between melanomas and melanocytic nevi seems feasible
      with a high rate of accuracy using multivariate logistic regression analysis. The
      proposed model is an alternative method to aid in early melanoma diagnosis.
      Expensive and sophisticated equipment is not required and it can be easily
      implemented in a reasonably priced portable programmable computer, in order to
      predict previously undiagnosed skin melanoma before histopathology results
      confirm diagnosis.

PMID- 16650168
TI  - Dermatosurgical techniques for repigmentation of vitiligo.
AB  - There are a number of dermatosurgery techniques available to achieve
      repigmentation of vitiligo, such as suction blister grafting, split-thickness
      skin grafting, punch grafting, follicular grafting, cultured-melanocytes
      transplantation, and noncultured-melanocytes transplantation. Each method has
      advantages and disadvantages. As there are no specific data available from the
      prospective studies in this field it is uneasy to recommend which surgical
      approach to vitiligo offers the best result. According to a systematic review by
      Njoo et al.,(17) suction blister and split-thickness skin grafting have the
      highest rates of success (87%), while the average success rates for other methods
      varied from 13% to 53%. Punch grafting has the highest rate of adverse effects,
      including cobblestoning appearance (27%) and scar formation (40%) in the donor
      site. Accordingly, it is also mandatory to appropriately select vitiligo patients
      in order to achieve a complete and permanent repigmentation.

PMID- 16650169
TI  - Impact of psoriasis on quality of life in Kuwait.
AB  - BACKGROUND: Psoriasis can seriously affect the quality of life (QOL) of patients
      and has a strong impact on social relations, psychological status and daily
      activities. OBJECTIVE: The aim of this study was to describe the impact of
      different grades of severity in psoriasis on QOL in patients in Kuwait.
      PATIENTS/METHODS: We used the Dermatology Quality Of Life scale (DQOLS) developed
      by Morgan and then validated for use in Kuwait to study a sample of 330 out
      patients with psoriasis. RESULTS: Overall, physical activities were affected in
      greater than 50% of cases. This figure increased significantly with increased
      severity of psoriasis. Also, social relationships were disrupted in more than
      half of the patients but with no significant difference between different grades
      of severity. All psychological feeling items were affected by psoriasis to
      variable degrees. However, significant differences related to the severity of
      psoriasis were detected: feeling embarrassed, feeling short tempered, feeling
      depressed, and feeling a lack of hope. One third of cases declared their sexual
      activities were affected by psoriasis. CONCLUSION: Data provided should improve
      the physicians' awareness of the importance of patients' QOL and enhance
      psychological evaluation of the psoriatic patient which will promote his/her
      positive outcome and compliance with treatment.

PMID- 16650170
TI  - Pemphigus vegetans of the oral cavity.
AB  - BACKGROUND: Pemphigus vegetans, a variant of pemphigus vulgaris, constitutes a
      rare form of all pemphigus cases, and oral involvement is common. Two clinical
      subtypes of pemphigus vegetans exist, characterized initially by flaccid bullae
      and erosions (Neumann) or pustules (Hallopeau). Both subtypes subsequently
      develop into hyperpigmented vegetative plaques with pustules and hypertrophic
      granulation tissue at the periphery. METHODS: We report three cases of pemphigus
      vegetans with oral manifestations exclusively. Two patients were male aged 30 and
      45 years old, respectively, while one was a 51-year-old female. CONCLUSION: Oral
      lesions in all cases consisted of erosions and whitish, vegetating plaques. The
      histopathological characteristics were in all cases identical. The spinous cell
      layer was characterized by intense acanthosis and by the presence of vesicles
      between the spinous and basal cell layers. Inside the vesicles exudative elements
      were observed consisting mainly of eosinophils. In the upper lamina propria
      severe inflammatory reaction was observed. Streptavidin-biotin immunoperoxidase
      technique showed in all cases intercellular epithelial deposition of IgG and C3.

PMID- 16650171
TI  - Cutaneous phaeohyphomycosis caused by an Itraconazole and Amphoterecin B
      resistant strain of Veronaeae botryosa.
AB  - BACKGROUND: Although the dematiaceous fungus Veronaea botryosa is rarely
      encountered clinically, it can be pathogenic. METHODS: A patient with a history
      of diabetes mellitus, coronary artery disease, and Cushing's syndrome had
      recurrent multifocal, crusted, brownish-red noduloplaques on the right forearm,
      left upper limb, and right knee. A skin biopsy was obtained for histopathology
      and fungal cultures. RESULTS: The histopathology showed brownish hyphae and yeast
      like cells scattered in granulomatous infiltrates. Slide cultures revealed erect
      and straight conidiophores with two-celled cylindrical conidia, which have round
      tops and truncated bases. The fungus was identified as Veronaea botryosa. The
      disease slowly progressed despite a 6-month itraconazole regimen (200 mg daily).
      Subsequent use of Amphoterecin B produced only mild clinical improvements.
      Susceptibility tests showed resistance to both agents. CONCLUSIONS: Cutaneous
      phaeohyphomycosis caused by V. botryosa is extremely rare. Antifungal
      susceptibility tests are important for choosing the appropriate drug and
      predicting the clinical outcome.

PMID- 16650172
TI  - Histoid leprosy - unusual presentation.
AB  - A 39-year-old man presented with a chronic nonhealing toe ulcer and multiple skin
      colored papules on the back, arms, and knees. From an initial small erosion, the
      toe lesion ulcerated over a 1.5-year period, while the papules progressed over a
      6-month period, first appearing on the back and then spreading to the arms and
      knees. The past medical and family history were non-contributory. Pertinent
      findings included the aforementioned well-defined, asymmetric, shiny papules
      (Fig. 1). There were multiple, discrete, erythematous, pedunculated, tumor-like
      masses of various sizes over the right thigh (Fig. 2) and a well-defined 4 cm x 3
      cm ulcer on the second toe of the left foot, the floor of which was covered by
      necrotic slough. There was distal loss of sensation to temperature, touch, and
      pain. The greater auricular, ulnar, radial cutaneous and common peroneal nerves
      were thickened bilaterally, but non-tender. A clinical diagnosis of histoid
      leprosy was made. The differential diagnosis for the tumor-like thigh masses
      included dermatofibroma, neurofibroma, and Kaposi's sarcoma. The hemogram,
      liver/renal function tests, chest X-ray, and abdominal ultrasound were normal.
      Human immunodeficiency virus enzyme-linked immunosorbent assay (HIV ELISA) was
      negative. The ear lobe smear (ELS) for acid-fast bacilli showed a bacterial index
      (BI) of 6+[> 1000 organisms/oil immersion field (oif)] and a morphological index
      (MI) of 50%. The skin-colored papules on the back and the pedunculated masses
      showed a BI of 5+ (100-1,000 organisms/oif) and an MI of 50%. The normal skin
      showed a BI of 4+ (10-100 organisms/oif) and an MI of 5%. Biopsy of the papules
      and pedunculated tumors showed a well-circumscribed area of the dermis packed
      with many acid-fast organisms and foamy macrophages, consistent with histoid
      leprosy (Fig. 3). Fite-Faraco stain demonstrated cells packed with lepra bacilli.
      A final diagnosis of lepromatous leprosy, histoid variant, was made. Dapsone,
      clofazimine, rifampicin, and, later, ofloxacin were started.

PMID- 16650173
TI  - Coexistence of a systemic lupus erythematosus and porphyria cutanea tarda: case
      successfully improved by avoidance of sun exposure.

PMID- 16650174
TI  - (Juvenile) Pityriasis rubra pilaris.

PMID- 16650175
TI  - Cutaneous T-cell lymphoma with HTLV-I infection: clinical overlap with adult T
      cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a malignant proliferation of mature
      helper T lymphocytes,(1) and is caused by human T-lymphotropic virus type I (HTLV
      I);(2) an HTLV-I infection endemic in the Caribbean, south-western Japan, South
      America and Africa.(3,4) Seroepidemiological studies suggest that it is also
      endemic in Brazil.(5) Although carriers of HTLV-I show polyclonal integration of
      virus in T lymphocytes, only patients with ATLL of various subtypes show
      monoclonal integration of HTLV-I in tumor cells.(6,7) Cutaneous T-cell lymphomas
      (CTCL) are a group of primary cutaneous lymphoproliferative diseases(8) with
      unknown etiology.(9) The two most common presentations of CTCL are mycosis
      fungoides (MF) and Sezary syndrome (SS).(10-13) However, both CTCL categories can
      easily resemble ATLL. Therefore, in HTLV-I endemic areas, differentiation between
      ATLL and CTCL must be performed, as they have different prognoses and treatment
      approaches.(14).

PMID- 16650176
TI  - Disseminated sporotrichosis mimicking sarcoidosis.
AB  - A 40-year-old Caucasian man presented to the dermatology clinic at Baylor College
      of Medicine, Houston, Texas, in February 2003, for the evaluation of three
      nonhealing ulcers. The patient's past medical history was significant for
      hypothyroidism and pulmonary sarcoidosis, the diagnosis of which was made in June
      2000. In March 2000, the patient had complained of cough and shortness of breath.
      A purified protein derivative (PPD) (Mantoux text) was negative. Computed
      tomography (CT) scans of the chest revealed diffuse hilar and mediastinal
      adenopathy and bilateral interstitial and alveolar infiltrates. Although
      consistent with sarcoidosis, these findings were insufficient to exclude other
      etiologies, including disseminated fungal infection. Cultures and stains of
      subsequent bronchoscopy specimens failed to reveal any organisms, and
      histopathologic evaluation of the specimens was nondiagnostic. Based on the
      imaging studies and the negative cultures, a diagnosis of sarcoidosis was made,
      and the patient was started on therapy with prednisone. Before coming to our
      clinic, the patient had been on several courses of prednisone. In May 2002, the
      patient had presented to a private dermatologist with a 1-year history of a
      nonhealing 2.4 cm x 2.0 cm ulcer on the left medial forearm. Two biopsies were
      reported as nondiagnostic. The patient's presentation was interpreted as most
      consistent with Mycobacterium marinum infection, and so he was empirically
      treated with minocycline. This treatment was continued for almost 3 months
      without improvement in the ulcer. A few months after the minocycline had been
      discontinued, the patient was treated empirically for 2 months with
      ciprofloxacin. This treatment was also unsuccessful in ameliorating the ulcer. In
      between the two courses of antibiotics, specimens from the lesion were sent for
      bacterial and fungal cultures, which revealed normal skin flora. In January 2003,
      the patient returned to his private dermatologist with three ulcerations. In
      addition to the nonhealing ulcer on his left forearm, which he had acquired
      several months earlier, he had also developed a 3.0 cm ulcer on his right arm and
      a 3.0 cm ulcer on his central back. The patient refused biopsies at this visit.
      Given the patient's previous diagnosis of pulmonary sarcoidosis, it was thought
      that the skin lesions might represent ulcerative cutaneous sarcoidosis. Pyoderma
      gangrenosum was also considered to be a likely diagnosis. Therefore, the patient
      was started on a course of oral prednisone, an effective therapy for both
      sarcoidosis and pyoderma gangrenosum. Despite 1 month of treatment with 60 mg/day
      of prednisone, the ulcers increased, and the patient was subsequently referred to
      our clinic. Physical examination at the time of presentation revealed steroid
      acne on the trunk and upper extremities and three non-tender ulcers with
      erythematous, undermined borders (Figs 1-3). On the left arm, there was an
      adjacent nodule which the patient attributed to a scar from a previously healed
      ulcer. Histologic examination of biopsy specimens from all three sites showed
      similar findings. The lesion contained diffuse, suppurative, granulomatous,
      inflammatory infiltrates with extensive central necrosis. The infiltrates were
      composed of histiocytes, multinucleated foreign-body-type giant cells, plasma
      cells, lymphocytes, neutrophils, and neutrophil fragments. No organisms were seen
      in the initial, routinely stained sections. However, periodic acid-Schiff (PAS)
      staining demonstrated small fungal spores (Fig. 4) morphologically consistent
      with sporotrichosis, within the cytoplasm of multinucleated histiocytic giant
      cells (Fig. 5). Additional stains for bacteria and acid-fast organisms were
      negative. Cultures of the biopsy specimens from all three sites grew Sporothrix
      schenckii. Further questioning of the patient failed to reveal an obvious source
      of the infection. The patient denied any history of traumatic skin inoculation
      and did not engage in gardening or other outdoor activities that are classically
      associated with sporotrichosis. The patient did admit to blackberry picking on
      detailed retrospective questioning. Once the diagnosis of sporotrichosis was
      made, the patient was given 200 mg/day of itraconazole. After 2 months, the
      patient's ulcers were almost completely healed. The patient's pulmonary
      complaints were also much improved.

PMID- 16650177
TI  - Is Kikuchi-Fujimoto disease a manifestation of systemic lupus erythematosus?
AB  - A 32-year-old woman presented with fever and swelling in the axillae of 2 months'
      duration, and erythema of the face, fluid-filled lesions on the trunk, oral
      ulcers, crusting of the lips, and redness and watering of the eyes for 3 days.
      The patient was initially diagnosed with tuberculous lymphadenitis and was given
      antituberculous treatment. One month later, she developed the present complaints
      (see below). The patient was photosensitive. There was no joint pain or Raynaud's
      phenomenon. She had experienced three intrauterine deaths in the past with no
      live births. On examination, the patient was pale. Bilateral axillary
      lymphadenopathy was present. The lymph nodes were mobile, non-tender, and not
      matted. Mucocutaneous examination revealed a malar eruption, flaccid bullae on
      the back (Fig. 1), crusting of the lips (Fig. 2), oral ulcers, and redness and
      discharge from the eyes. On investigation, immunoglobulin G (IgG), IgM, and IgA
      for tuberculosis were negative. There was anemia and leukopenia, the erythrocyte
      sedimentation rate (ESR) was raised, albumin in urine was positive, enzyme-linked
      immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative,
      and venereal disease research laboratory (VDRL) test was nonreactive. Antinuclear
      antibody (ANA), dsDNA, and antiphospholipid antibody were positive. Fine needle
      aspiration cytology (FNAC) of the axillary lymph node showed loss of nodal
      architecture. The extensive infiltrate consisted of lymphocytes, histiocytes,
      immunoblasts, and necrosis of cortical and paracortical areas. There was
      histiocytic necrotizing lymphadenitis without granulocytic infiltration. These
      features were suggestive of Kikuchi-Fujimoto's disease (Fig. 3). Skin biopsy
      showed epidermal atrophy, basal cell vacuolation, focal hyperkeratosis,
      pilosebaceous atrophy, and follicular plugging. The dermis showed edema and a
      lymphocytic infiltrate in the upper dermis and around the blood vessels. These
      features were suggestive of systemic lupus erythematosus (SLE). Direct
      immunofluorescence of lesional skin showed a strong continuous basement membrane
      zone (BMZ) band of C3 and fibrinogen and a strong discontinuous granular BMZ band
      of IgG. IgA was negative. Covered skin showed moderate and strong positivity for
      IgM and IgG, respectively. C3, IgA, and fibrinogen were negative. These findings
      were suggestive of SLE (Fig. 4). Based on the clinical findings and
      investigations, a diagnosis of Kikuchi-Fujimoto's disease with SLE was made.

PMID- 16650178
TI  - A case of recurrent Sweet's syndrome in an 80-year-old man: a clue to an
      underlying malignancy.
AB  - An 80-year-old man presented with multiple erythematous papules on the trunk and
      extremities of a few weeks' duration. He had no past medical or family history of
      skin diseases or any other medical diseases. A biopsy showed a perivascular
      lymphohistiocytic infiltrate and sparse neutrophils with several atypical
      lymphocytes in the deeper dermis. With an initial diagnosis of T-cell
      pseudolymphoma or unspecified neutrophilic dermatosis, he showed a brisk response
      to an intramuscular injection of triamcinolone acetonide (40 mg/mL). After 1
      month, his skin lesion recurred. Steroid was given with a good clinical response.
      One month later, however, his skin lesion relapsed. At this time, he presented
      with disseminated pustulopapular lesions on the trunk and extremities.
      Examination revealed multiple, variable-sized, erythematous plaques with central
      pustules on the extremities (Fig. 1). The mucous membranes were not involved. He
      had no pain or tenderness. He had no systemic symptoms. Laboratory tests showed a
      hemoglobin level of 10.3 g/dL, a leukocyte level of 6,900/mm(3), with an
      increased proportion of segmented nuclear neutrophils (83%), and an elevated C
      reactive protein. A skin biopsy revealed a dense perivascular and interstitial
      infiltrate composed of neutrophils with marked dermal edema (Fig. 2). Sweet's
      syndrome was the final diagnosis and he was treated with oral prednisolone (30-40
      mg/day) and dapsone (50 mg/day) for 2 months. As this 80-year-old patient had a
      recurrent history of similar skin lesions and anemia, an underlying hematologic
      malignancy was suspected. A bone marrow biopsy showed typical myelodysplastic
      syndrome (MDS). The hemoglobin level was decreased to 5.3 g/dL during a follow-up
      period of 5 months. The skin lesions recurred despite oral steroids and dapsone.
      The patient received only symptomatic treatment, such as a transfusion, for the
      underlying malignancy MDS.

PMID- 16650179
TI  - Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting
      herbal extract: implication for the mechanism underlying elastase-associated
      wrinkles.
AB  - BACKGROUND: Previously, we have demonstrated that fibroblast-derived elastase
      plays an essential role in the increased three-dimensional tortuosity of elastic
      fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This
      decrease in skin elasticity is closely associated with the formation of wrinkles
      induced by UV exposure. OBJECTIVE: To further clarify the role of elastase in the
      formation of wrinkles induced by UV exposure, we assessed the effects of an
      extract of Zingiber officinale (L.) Rose (which inhibits fibroblast-derived
      elastase) on the wrinkle formation induced by chronic UV-B irradiation. RESULTS:
      Topical application of an extract of Zingiber officinale (L.) Rose to rat or
      hairless mouse skin significantly inhibited the wrinkle formation induced by
      chronic UV-B irradiation at a suberythemal dose, which was accompanied by a
      significant prevention of the decrease in skin elasticity in both types of animal
      skin. In the rat hind limb skin, consistent with the inhibition of reduced skin
      elasticity, wrinkle prevention occurred concomitantly with a significant decrease
      in the curling and three-dimensional tortuosity of dermal elastic fibers.
      CONCLUSION: Our results indicate that herbal extracts with an ability to inhibit
      fibroblast-derived elastase may prove to be effective as anti-wrinkling agents,
      confirming the important role of elastase in UV-B-induced wrinkle formation.

PMID- 16650180
TI  - Levocetirizine is an effective treatment in patients suffering from chronic
      idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel,
      multicenter study.
AB  - BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily
      presence of urticaria for at least 6 weeks without an identifiable cause.
      Symptoms include short-lived wheals, itching, and erythema. CIU impedes
      significantly a patient's quality of life (QoL). Levocetirizine is an
      antihistamine from the latest generation approved for CIU. AIM: To investigate
      the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of
      CIU, as well as for the QoL and productivity. METHODS: The primary criteria of
      evaluation were the pruritus severity scores over 1 week of treatment and over 4
      weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI).
      RESULTS: Baseline pruritus severity scores were comparable in the two treatment
      groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and
      demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy
      was maintained over the entire study period (4 weeks, P<0.001). The number and
      size of wheals were considerably reduced compared with placebo over 1 week and
      over the total treatment period (P <or= 0.001). This was paralleled by an
      improvement in the QoL (DLQI: 7.3 units in the levocetirizine group and 2.4 units
      in the placebo group) and a higher productivity at work in the levocetirizine
      group (3.0 workdays lost per patient per month in the placebo group, 0.3 in the
      levocetirizine group). No unexpected adverse events occurred. CONCLUSIONS:
      Levocetirizine, 5 mg once daily, is an effective treatment for CIU, characterized
      not only by a rapid and sustained response, but also by an important improvement
      in QoL.

PMID- 16650184
TI  - Dirofilaria repens: a dog parasite presenting as a paranasal subcutaneous nodule.

PMID- 16650185
TI  - Spontaneous repigmentation in vitiligo: why it is important.

PMID- 16650186
TI  - Toxic epidermal necrolysis caused by tetrazepam.

PMID- 16650187
TI  - Treatment of extensive and recalcitrant viral warts with acitretin.

PMID- 16650188
TI  - Scalp abscess due to Enterobacter agglomerans.

PMID- 16650190
TI  - Democracy or dictatorship at the bedside?

PMID- 16650191
TI  - Changing attitudes to the management of ischaemic stroke between 1997 and 2004: a
      survey of New Zealand physicians.
AB  - AIM: In 1997, a survey of New Zealand physicians' opinions on the management of
      stroke was carried out. Since then, there have been a number of advances in
      stroke therapy. We have repeated the 1997 survey to assess changes in physicians'
      opinions on stroke management. METHODS: A questionnaire was sent to 293
      physicians responsible for patients admitted with acute stroke to hospitals
      throughout New Zealand. It included questions on the management of acute stroke
      and secondary prevention and was based on the 1997 questionnaire. RESULTS:
      Responses were received from 211 physicians of whom 174 (82%) managed patients
      with an acute stroke. The number of respondents who thought that stroke units
      were efficacious has increased (57% in 1997 to 89%, P < 0.001). The use of
      aspirin acutely (P < 0.001) and intravenous tissue plasminogen activator (P =
      0.006) has also increased. In 2004, antihypertensive therapy for secondary stroke
      prevention would be commenced if the blood pressure was 150/90 by 98% of
      respondents and 140/90 by 70% of respondents. In 2004, a statin would be
      commenced if the total cholesterol level was 4.0 mmol/L by 56% of respondents and
      5.0 mmol/L by 91% of respondents. CONCLUSIONS: This survey has shown important
      changes in the management of ischaemic stroke over the past 7 years.

PMID- 16650192
TI  - Diagnosis of pulmonary embolus using ventilation/perfusion lung scintigraphy:
      more than 0.5 segment of ventilation/perfusion mismatch is sufficient.
AB  - BACKGROUND: To determine the optimal diagnostic cut-off point using a simplified
      criterion for the detection of pulmonary embolus (PE) and to evaluate the
      criterion's utility and reporter reproducibility. METHODS: Lung scintigraphy was
      carried out in 924 patients for the diagnosis of PE. This group consisted of 316
      men and 608 women with median age of 63 years (range 18-94 years). Ventilation
      imaging was carried out with Tc-99m Technegas followed by perfusion imaging using
      190 MBq Tc-99m macroaggregated albumin. Studies were classified using a 6
      category probability criterion of incremental ventilation/perfusion (V/Q)
      mismatch: A, normal; B, low (minor matched V/Q defects or segmental matched V/Q
      defects without opacity on chest X-ray); C, low-moderate (a partial segment of
      V/Q mismatch); D, moderate (1 segment of mismatch); E, moderate-high (1-2
      segments of V/Q mismatch) and F, high probability (=2 segments of V/Q mismatch).
      Clinical end-points at 3 and 6 months were death by PE or PE treated with
      anticoagulation therapy. Three-reporter reproducibility was determined by kappa
      statistic on a subgroup of patients (53/924). RESULTS: A total of 122 patients
      (13%) had a confirmed diagnosis of PE at 3 months and no additional cases were
      registered at 6 months. The lung scintigraphy probability classification showed:
      normal 152 (16%), low 620 (67%), low-moderate 20 (2%), moderate 28 (3%), moderate
      high 24 (3%) and high 80 (9%). The respective sensitivities and specificities,
      where the diagnostic cut-offs were established at F, high; E, moderate-high; D,
      moderate and C, low-moderate probability, were F, 64 and 100%; E, 82 and 99%; D,
      95 and 98% and C, 98 and 96%. The respective false-negative cases for F, E, D and
      C cut-offs were 44, 22, 7 and 3. Using the revised Prospective Investigation of
      Pulmonary Embolism Diagnosis reporting classification reporter agreement showed
      kappa values of 0.31-0.48. Using a simplified 2-category (>0.5 segment of V/Q
      mismatch positive, all others negative) criterion resulted in a higher reporting
      agreement (kappa 0.74-0.83). There were only 3% of indeterminate cases if this
      was defined by the D category and a maximum of 8% if categories C, D and E were
      included. CONCLUSIONS: Using a simplified diagnostic criterion where all studies
      showing >0.5 segments of V/Q mismatch are regarded as positive and all others as
      negative, lung scintigraphy, incorporating Tc-99m Technegas ventilation imaging
      or its equivalent, can achieve a very high diagnostic accuracy for the detection
      of PE. Using this technique, less than 5% of scans are indeterminate. A
      simplified, unambiguous approach to reporting is recommended.

PMID- 16650193
TI  - Monitoring the use of amiodarone: compliance with guidelines.
AB  - AIM: Careful monitoring of amiodarone is recommended because it produces a range
      of potentially severe adverse effects. The aim of this study was to compare
      existing practice at our hospitals with the current international guidelines for
      the use of this drug. METHODS: A retrospective audit was carried out on all
      patients aged 15 years or older, with a primary discharge diagnosis of
      tachyarrhythmia and who were commenced and discharged alive on amiodarone between
      1 January 2000 and 30 June 2002 from Wellington and Kenepuru Hospitals, Capital
      and Coast District Health Board, Wellington, New Zealand. The medical records
      were examined for baseline measurements of renal, liver, thyroid and pulmonary
      function, the electrocardiogram and chest X-ray. Follow-up arrangements were
      sought postdischarge. A questionnaire was sent to the general practitioner
      requesting information on follow-up testing. RESULTS: During the trial period,
      743 patients were admitted with a primary diagnosis of tachyarrhythmia. Eighty
      six patients satisfied the entry criteria, and of these 58 were followed for at
      least 1 year postdischarge. Baseline testing of the electrocardiogram, full blood
      count and renal function testing was excellent (95-100%). Chest X-rays were
      carried out in 80% of patients. Baseline testing of thyroid (61%) and liver (44%)
      function was suboptimal. Two percent of patients had pulmonary function testing
      and no patient had a formal eye examination. At 6 months, only 32% had thyroid
      function tests and 41% had liver function tests. At 1 year, of those still on
      treatment, 35% had both liver and thyroid function tests. CONCLUSION: Monitoring
      of thyroid, liver and pulmonary function tests in patients on amiodarone is less
      than ideal. This is probably because of lack of awareness of current guidelines.

PMID- 16650194
TI  - Significant exercise-induced hypoxaemia with equivocal desaturation in patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The wide 95% confidence interval for S(a)O2 measured by pulse
      oximetry (S(P)O2) and the inherent characteristics of the oxyhaemoglobin
      dissociation curve can lead to modest but significant decreases in P(a)O2
      (deltaP(a)O2 > or = 5 mmHg) that may be under-appreciated. AIM: To avoid missing
      potentially significant deltaP(a)O2 by using S(P)O2, this study establishes a
      threshold of deltaS(P)O2 to detect deltaP(a)O2 by examining the correlation
      between deltaS(P)O2 and deltaP(a)O2. METHODS: We enrolled 29 elderly patients
      with moderate to severe chronic obstructive pulmonary disease as assessed by lung
      function testing. Arterial blood gases and S(P)O2 measurements were carried out
      during maximal exercise testing. The patients were assigned to groups based on
      P(a)O2 measurements: group 1 had P(a)O2 at peak exercise (P(a)O2peak) > or = 60
      mmHg without a deltaP(a)O2; group 2 had P(a)O2peak > or = 60 mmHg with a
      deltaP(a)O2; group 3 had P(a)O2peak < 60 mmHg without a deltaP(a)O2; and group 4
      had P(a)O2peak < 60 mmHg with a deltaP(a)O2. RESULTS: The study population was
      evenly distributed between groups 1, 2 and 4. However, group 3 did not have any
      patients enrolled in this study that met group 3 criteria. The sensitivity of
      pulse oximetry required to detect S(a)O2 below 90% was 19%. DeltaS(P)O2 of 3% may
      increase the low sensitivity of S(P)O2 and was shown by a 92% positive predictive
      value for deltaP(a)O2 > or = 5 mmHg. CONCLUSION: This study suggests that
      important changes in oxygenation may be avoided if using deltaS(P)O2 rather than
      absolute values of S(P)O2 in patients with chronic obstructive pulmonary disease
      undergoing exercise testing to detect exercise-induced hypoxaemia.

PMID- 16650195
TI  - Adolescent and young adult cancer: a revolution in evolution?
AB  - The optimal management of adolescent and young adult cancer has been the subject
      of vigorous debate in paediatric and adult cancer community for many years. This
      debate is rapidly coming to the boil. There is international recognition that not
      only is cancer in young people on the rise but also that improvements in outcomes
      of cancer in young people lag well behind the advances that have been achieved
      for both children and older adults in the past 30 years. The underlying problems
      appear to relate to a complex set of interactions between the health-care system
      and the prevalence of cancer in this age group and the unique psychosocial and
      educational needs of this population. This article explores why we should be
      concerned about Australian health outcomes in this group and considers how best
      we might respond to these concerns.

PMID- 16650196
TI  - Coxibs, non-steroidal anti-inflammatory drugs and cardiovascular risk.
AB  - The introduction of selective cyclooxygenase-2 inhibitors offered the promise of
      similar efficacy in pain control without the gastrointestinal effects associated
      with non-selective non-steroidal anti-inflammatory drugs (NSAIDs). By blocking
      prostacyclin formation but leaving platelet-derived thromboxane A2 generation
      unopposed, there is concern that the potential gastrointestinal benefit of
      cyclooxygenase-2-selective inhibitors may come at the cost of increased
      thrombotic risk. However, the differential effects of coxibs on blood pressure,
      endothelial function, oxidative stress, tissue factor expression, vascular smooth
      muscle proliferation and neointimal hyperplasia indicate a distinct heterogeneity
      among this class of drugs. Importantly, the observation of an excess
      cardiovascular risk with traditional NSAIDs in randomized clinical trials, meta
      analysis and large-scale observational studies further highlights the need to
      scrutinize the entire class of anti-inflammatory drugs, including traditional
      NSAIDs, as rigorously as coxibs.

PMID- 16650197
TI  - 'On being both professional and human': a response.
AB  - A recent publication in the Internal Medicine Journal touches on some sensitive
      points. It emphasizes deficiencies in communication between doctors and patients
      and between doctors and families of the patients, particularly in extreme medical
      circumstances that are likely to end in death. It stresses as well the trauma of
      seeing a loved one reduced from a human being with a distinctive biography to an
      impersonal clinical problem. Such articles have a long history but seldom produce
      any change in the attitudes or practices of the medical profession. There seem to
      be a number of reasons for this, including clinicians' ambivalence towards the
      real importance of ethics in medicine and the lack of a forum in which consumers
      and doctors might air and discuss their experiences of suffering and
      disappointment. A forum for mutual discussion is suggested as the most
      constructive step to take. Medical education has not proven to be an answer to
      the problems of sensitive communication.

PMID- 16650198
TI  - One woman's journey is a journey we all may share.
AB  - In recent years, there has been a growing awareness of the need to take account
      of the patient's own experience of illness. Although this is to be welcomed, it
      is also important to hear the stories of those most affected by the patient's
      illness, their partners, their families, their communities and those who care for
      them. 'On being both professional and human: one woman's journey' provides a
      powerful example of how narrative may assist clinicians to learn about
      communication, care, presence and the effect of illness and death on those left
      behind.

PMID- 16650199
TI  - All troponins are not created equal.
AB  - Troponin measurement is central to the management and risk stratification of
      acute coronary syndromes. Decisions are made by categorizing troponin as positive
      or negative. We sought to evaluate categorical agreement between four troponin
      assays. Sixty blood samples were analysed by three troponin I assays (Centaur,
      Architect and point-of-care i-STAT) and one troponin T (TnT) assay (Roche
      Elecys). The upper reference limit was taken as the lowest value with a
      coefficient of variation of 10% or less. Continuous agreement between assays was
      good (Pearson's correlation coefficient 0.871-0.995). Categorical agreement
      assessed by Cohen's kappa varied from poor (between Architect and Centaur kappa =
      0.37, and between TnT and Centaur kappa = 0.48) to good (between Architect and i
      STAT kappa = 0.68, and between TnT and i-STAT kappa = 0.68). Percentage of
      positive results varied almost twofold, from 37% for the Centaur to 72% for the
      Architect. Comparison of four troponin assays showed up to twofold variations in
      the proportion of positive results. This implies that either a large proportion
      of troponin-positive diagnoses are missed by some assays or the assays with
      higher positivity are generating large numbers of false positives. Clinicians
      should evaluate troponin results in the clinical context and not base decisions
      solely on the 'normal range' of their local troponin assay.

PMID- 16650200
TI  - Cardiac involvement in Henoch-Schonlein purpura.
AB  - Cardiac involvement is not regarded as a feature of Henoch-Schonlein purpura
      (HSP). We report a patient with HSP who developed significant cardiac symptoms,
      which resolved with immunosuppression. We review previous cases of HSP with
      cardiac features, none of which showed a response to treatment, and discuss
      evidence that cardiac involvement is more common than recognized. The
      implications for investigation and treatment of this condition are discussed.

PMID- 16650201
TI  - Bilateral nephrocalcinosis in short bowel syndrome.

PMID- 16650203
TI  - Angiodysplasia and Noonan syndrome: a new association.

PMID- 16650204
TI  - On selection of medical students: a personal response.

PMID- 16650207
TI  - Preventing venous ulcer recurrence: a review.
AB  - This review article examines the available evidence on both the primary and
      secondary prevention of venous ulceration, exploring both the individual, social
      and financial implications of system failures that allow patients to remain at
      increased risk of recurrent ulceration. The role of both venous disease
      assessment and corrective superficial venous surgery are discussed in the light
      of recently published randomised controlled studies on the role of superficial
      venous surgery as both an adjunct to ulcer healing and ulcer prevention.

PMID- 16650208
TI  - Baclofen pump pocket infection: a case report of successful salvage with muscle
      flap.
AB  - Programmable pump for continuous infusion of intrathecal baclofen, an agonist of
      the inhibitory neurotransmitter gamma-aminobutyric acid, is nowadays being widely
      used to control spasticity. The most common complications leading to explantation
      of the pumps are skin breakdown and infection at the pump implantation site which
      cannot be effectively treated without pump removal. We report a 37-year-old man
      who developed a baclofen pump pocket infection that did not respond to antibiotic
      therapy. Because the continuation of intrathecal baclofen administration was
      critical to the patient, and because the high cost of the pump precluded its
      prompt replacement, the pump was salvaged using the ipsilateral rectus abdominis
      muscle that was elevated on its inferior vascular pedicle and wrapped around the
      pump. Abdominal skin was then approximated, leaving a small portion of exposed
      muscle overlying the refill site that was covered by a split-thickness skin
      graft. Continuous intrathecal baclofen administration was never discontinued.
      Three months later, the pump's refill site could be easily identified manually
      for pump refill. There were no signs of recurrent infection during the 2-year
      follow-up period.

PMID- 16650209
TI  - Wound-healing trajectories as outcome measures of venous stasis ulcer treatment.
AB  - Outcome measures of venous ulcer healing are not uniformly accepted. Stringent
      criteria of 100% closure fail to provide information of healing over the entire
      span of repair. Wound-healing trajectories (plot of percentage of wound closure
      versus time of wound treatment) were constructed for 232 patients treated in
      eight clinical trials at two independent wound care/research centres.
      Trajectories were constructed for ulcers that totally healed (100% closure) and
      those that did not (<100% closure) over a 20-week period. Kaplan-Meier survival
      plots determined the percentage of patients achieving total healing versus time
      of treatment. The wound-healing trajectories were almost identical for patients
      achieving complete ulcer healing, as were the trajectories for patients with less
      than 100% closure. The trajectories for the ulcers healing completely were
      significantly different from those with <100% closure. Only 60% of all patients
      achieved 100% closure by 20 weeks. Using linear regression, it was predicted that
      it would take 31 weeks for all patients to achieve total healing. Total healing
      is an inadequate outcome measure for healing of venous stasis ulcers. Clinical
      trials using this measure would require excessive time periods. As wound-healing
      trajectories for patients treated at two centres mimic one another, shifting the
      wound-healing trajectory from one of impaired healing to one of a more ideal
      healing course may be considered a better outcome measure for determining healing
      of venous stasis ulcers.

PMID- 16650210
TI  - Role of acellular dermal matrix allograft in minimal invasive coverage of deep
      burn wound with bone exposed--case report and histological evaluation.
AB  - A sandwich graft was applied to the debrided cortical bone layer of the tibia in
      the case of a 72-year-old male patient with full-thickness necrotic burn injury.
      The combined graft consisted of a dermal template material and autologous split
      thickness skin graft. After application, the graft was found totally accepted and
      provided good functionality with acceptable appearance. Histopathologic
      evaluation revealed a complete take with revascularisation of the implant.
      Supporting lamellar bony trabecules were also seen in the deep dermal dermis
      representing a connection to the underlying bone. The use of the dermal matrix in
      deep burn exposing the bone provides a satisfactory functional result and good
      cosmetic appearance.

PMID- 16650211
TI  - Investigation of risk factors for surgical wound infection among teaching
      hospitals in Tehran.
AB  - This prospective study was carried out to investigate the risk factors and
      incidence of surgical site infection (SSI) among patients in surgical wards of
      five hospitals affiliated to Iran University of Medical Sciences. Data was
      collected in a register card filled by specially trained staff. Nine-hundred and
      eighteen patients admitted in surgical wards were followed 30 days
      postoperatively for SSI during 1 April 2003 to 30 September 2003. A total of 77
      patients were identified among 918 cases included in the study, with a resulting
      overall SSI rate of 8.4%. The risk of SSI was increased by age older than 60
      years (OR = 3.9; P < 0.0001), diabetes mellitus (OR = 4.9; P < 0.0001), smoking
      (OR = 3.1; P < 0.0001), obesity (OR = 4.1; P < 0.0001) and wound drain (OR = 2.2;
      P < 0.0001). There were significant statistical difference in duration of
      anaesthesia (131.6 vs. 177 min, P < 0.001) and duration of surgery (99 vs. 140.5)
      between patients without SSI and patients with SSI. In conclusion, identification
      of the risk factors for SSI will help physicians to improve patient care and may
      decrease mortality and morbidity and hospital care costs of surgery patients.

PMID- 16650212
TI  - Penetrating zone II neck injury by broken windshield.
AB  - All penetrating neck wounds are potentially dangerous and require emergency
      treatment because there are important vessels, nerves and organs in the neck. We
      present the case of a patient who had an unusual penetrating neck injury caused
      by a broken windshield, noticed accidentally. Because fragments of windshield
      glass consist of sharp material, and the neck contains vital structures, such
      penetrating neck injury may cause life-threatening complications. Radiological
      examinations should be offered before the management of all neck wounds. The risk
      of retained foreign bodies and related complications can be prevented by using
      fluoroscopy during surgical exploration of the neck.

PMID- 16650214
TI  - Impairment of skin barrier function is not inherent in atopic dermatitis
      patients: a prospective study conducted in newborns.
AB  - We conducted a cohort study to determine whether the barrier dysfunction of the
      stratum corneum that facilitates the penetration of various exacerbating agents
      from the environment is inherent in atopic dermatitis patients as suggested by
      some dermatologists. Clinical observation and biophysical measurements of the
      skin were performed on the cheek and on the flexor forearm of 24 newborn infants
      once between 2 and 14 days postnatally and 1, 3, and 6 months later. Nineteen had
      atopic family histories. Most of the infants had physiologic neonatal xerosis
      that was observed as a reduced high-frequency conductance without any impairment
      in the stratum corneum barrier function assessed by transepidermal water loss.
      Four of the 24 neonates developed atopic dermatitis around 2 to 3 months after
      birth. In all of them, barrier impairment noted as increased transepidermal water
      loss was observed only after the development of skin lesions. During their
      neonatal period, their transepidermal water loss and skin surface hydration state
      were indistinguishable from those of the neonates whose skin remained lesion-free
      during the observation period. Therefore, we concluded that the barrier
      impairment found in atopic dermatitis is not inherent but represents a phenomenon
      secondary to dermatitic skin changes.

PMID- 16650215
TI  - Profile of childhood vitiligo in China: an analysis of 541 patients.
AB  - From July to December 2002, we collected data from 2247 vitiligo patients in
      order to establish the clinical and epidemiologic profile of vitiligo in China.
      Of these patients, 541 (24.1%) were children aged equal to or less than 12 years.
      Of the 541 children, 274 (50.6%) were boys and 267 (49.4%) were girls, with a
      mean age of 8.87 years and a mean onset age of 7.28 years. Similar to adult
      patients, boys and girls were affected by vitiligo with equal frequency. The most
      frequent age of onset was between 4 and 8 years (42.5%). The mean duration of
      vitiligo was 19.71 months (range: 0-132 months). The most common type of vitiligo
      was vitiligo vulgaris, the frequency of which was 38.1%, followed by focal
      vitiligo (34.6%), segmental vitiligo (19.4%), acrofacial vitiligo (7.6%), and
      universal vitiligo (0.4%). Segmental vitiligo had an earlier the other types. Of
      the 541 children with vitiligo, 60 (11.1%) had a family history, and 3 (0.6%) had
      more than one family member who was affected. Forty-one (7.6%) children had an
      associated autoimmune disease: halo nevi and alopecia areata, which were observed
      in 39 (7.2%) and 2 (0.4%) children, respectively.

PMID- 16650216
TI  - Patch testing of Singapore children and adolescents: our experience over 18
      years.
AB  - This is a retrospective epidemiologic study of allergic contact dermatitis in
      children and adolescents in Singapore who had undergone patch testing from
      January 1, 1986 to December 31, 2003. A total of 2,340 patients below the age of
      21 years had undergone patch testing. Of these, 1,063 (583 girls, 480 boys) were
      positive to one or more allergens. The most common allergens were: nickel (40%),
      thimerosal (15%), colophony (9%), lanolin (8%), cobalt (8%), fragrance mix (5%),
      and neomycin (4%). Each of these allergens will be discussed individually. This
      is the first study with over 1000 patients on this subject from Asia.

PMID- 16650217
TI  - Congenital syphilis.
AB  - Congenital syphilis is a rare and serious disease that, although preventable,
      continues to be a major healthcare problem. Its clinical spectrum ranges from an
      asymptomatic infection to fulminating sepsis or death. A diagnosis of congenital
      syphilis was made in an 8-week-old infant whose mother had adequate prenatal
      care. We present the clinical and histopathologic findings of this uncommon
      congenital disease.

PMID- 16650218
TI  - Neonatal pemphigus vulgaris in an infant born to a mother with pemphigus vulgaris
      in remission.
AB  - Neonatal pemphigus vulgaris is a rare autoimmune disease that is caused by
      transplacental passage of pemphigus vulgaris autoantibodies. The association of
      maternal pemphigus vulgaris with neonatal disease pemphigus vulgaris has been
      only rarely reported. We describe an infant with pemphigus vulgaris born to a
      mother whose disease was in remission.

PMID- 16650219
TI  - Cutaneous Infection with Mycobacterium abscessus in a child.
AB  - Nontuberculous mycobacteria can cause cutaneous infections in both children and
      adults. Localized nontuberculous mycobacterial infections of the skin have been
      reported in children following injections or surgical procedures. We report a
      child who developed a cutaneous nontuberculous mycobacterial infection after
      exposure of a skin wound to pond water. Cutaneous infection with the rapidly
      growing mycobacteria Mycobacterium abscessus was demonstrated by clinical and
      histologic evaluation on the lower leg of an otherwise healthy 12-year-old
      Caucasian boy. We describe this as an instance of an unusual acquisition of
      cutaneous M. abscessus infection in a child.

PMID- 16650220
TI  - Endemic pemphigus foliaceus in Venezuela: report of two children.
AB  - Two native Yanomami children from the Venezuelan Amazonia with erythroderma were
      hospitalized on our service. Clinical, histologic, and immunofluorescence studies
      diagnosed endemic pemphigus foliaceous. Human leukocyte antigen class II showed
      DRB1*04 subtype *0411, which has not been previously associated with this
      disease. However, it shares a common epitope with all the human leukocyte antigen
      DRB1 alleles that have been involved in this disease among Brazilian populations.
      Although this condition is endemic in Brazil, our patients are the first two
      reported in Venezuela.

PMID- 16650221
TI  - Progressive sclerodermatous skin changes in a child with phenylketonuria.
AB  - We report a child with phenylketonuria and unusually severe sclerodermatous skin
      changes. It is likely that prompt and aggressive therapy for these skin changes
      and phenylketonuria may have modified the clinical course.

PMID- 16650222
TI  - Hemorrhagic bullous lesions in a child with Henoch-Schonlein purpura.
AB  - An 8-year-old boy with Henoch-Schonlein purpura who developed hemorrhagic bullae
      is described. The occurrence of hemorrhagic bullae in children with Henoch
      Schonlein purpura is rare. A perusal of the literature revealed but seven
      occurrences to which we add another one.

PMID- 16650223
TI  - Holocarboxylase synthetase deficiency presenting as ichthyosis.
AB  - Holocarboxylase synthetase deficiency is a rare autosomal recessive disorder of
      biotin metabolism. Clinical manifestations usually present within the first few
      days of life and include severe acidosis, feeding difficulties, breathing
      abnormalities, vomiting, seizures, progressive loss of consciousness, coma, and
      death. Skin findings, when present, usually develop within the first weeks of
      life and are described as an erythroderma-like dermatitis involving the eyebrows,
      eyelashes, and scalp. We were asked to consult on a newborn with a collodion
      membrane and severe metabolic acidosis who was eventually diagnosed with
      holocarboxylase synthetase deficiency and ichthyosis. The diagnosis of
      holocarboxylase synthetase deficiency might be considered in a newborn with
      collodion membrane, ichthyosis, and acidosis.

PMID- 16650224
TI  - POEMS in childhood.
AB  - A 17-year-old boy had a 3-year history of diabetes mellitus, malabsorption
      syndrome, and skin changes consisting of induration, hyperpigmentation, and
      hypertrichosis on the anterior aspect of both thighs, lower abdomen, and scrotum.
      Physical examination found hypogonadism, hepatomegaly, gynecomastia, growth
      retardation, and ankle edema. There was no neuropathy or plasma cell dyscrasia.
      However, the characteristic skin changes and the combination of symptoms suggest
      polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes
      syndrome. This is a rare multisystemic disorder of obscure pathogenesis and no
      conspicuous heredity. Overproduction of vascular endothelial growth factor is
      thought to cause microangiopathy, neovascularization, and accelerated
      vasopermeability causing the multiorgan deterioration. Cyclophosphamid cytostatic
      therapy seems beneficial.

PMID- 16650225
TI  - Multiple trichoepitheliomas in the lines of Blaschko.
AB  - We report a unique occurrence of linear multiple trichoepitheliomas that follow
      Blaschko lines on the face of an otherwise healthy 8-year-old African American
      girl. Per the mother, the lesions had been present since birth. The diagnosis was
      made based on the histologic presence of palisading basaloid cells surrounding
      central areas of follicular differentiation and papillary mesenchymal bodies. To
      the authors' best knowledge, this is the first report of linear multiple
      trichoepitheliomas following the lines of embryologic cutaneous cell development,
      and possibly, the first of congenital multiple trichoepitheliomas.

PMID- 16650226
TI  - Two young girls with lipoblastoma and a review of the literature.
AB  - Lipoblastoma is an uncommon, benign tumor of embryonic adipose tissue that occurs
      predominantly in the pediatric population. It most often presents on the
      extremities. Biopsy of the lesion is standard for diagnosis, as clinical and
      radiologic diagnoses can be misleading. A complete yet conservative surgical
      excision is the preferred treatment modality. We describe two young girls with
      lipoblastoma and review the dermatologic literature. Initial biopsy of the lesion
      in these two patients was not diagnostic. Both tumors were excised and subsequent
      gross and histopathologic examination demonstrated features of lipoblastoma.

PMID- 16650227
TI  - Simultaneous multiple pilomatrixomas.
AB  - We report a 10-year-old girl with synchronous multiple pilomatrixomas.
      Pilomatrixomas are generally solitary tumors; synchronous multiple tumors are
      very rare. Multiple or recurring tumors may be found in association with various
      syndromes, and multiple tumors may be familial. Concurrent disorders were not
      identified in our patient and the etiology of her pilomatrixomas was not
      understood. Thorough examination of the patient and long-term follow-up are
      necessary with these tumors.

PMID- 16650228
TI  - Idiopathic disseminated comedones in a child.
AB  - An 11-year-old girl had an uncountable number of hyperkeratotic comedo-like
      lesions on her shoulders, arms, buttocks, and thighs, present for 5 years.
      Depressed scars, cysts, and small purulent nodules were observed in involved
      areas. Her 6-year-old brother does not have similar lesions. Other members of her
      family were not available for examination. Light microscopy showed dilated
      elongated infundibula filled with corneocytes and arranged in a lamellated
      pattern. A peri-infundibular inflammatory infiltrate was present.

PMID- 16650229
TI  - Localized epidermolysis bullosa simplex with generalized enamel hypoplasia in a
      child.
AB  - Epidermolysis bullosa is an uncommon disease characterized by the formation of
      blisters following minor trauma. The three major types are simplex, junctional,
      and dystrophic. Generalized enamel hypoplasia is accepted as a feature of the
      junctional type. Teeth with enamel hypoplasia are liable to destruction in the
      form of caries and/or gingivitis. In this report, a patient with epidermolysis
      bullosa simplex and severe enamel hypoplasia is described and the importance of
      early dental consultation for all children with this disease is stressed.

PMID- 16650230
TI  - Growth, bone mineral accretion, and adrenal function in glucocorticoid-treated
      infants with hemangiomas-- a retrospective study.
AB  - Hemangiomas, common proliferative vascular tumors, can grow rapidly in the first
      months of life. Although therapy with high-dose oral glucocorticoids is standard
      for lesions that threaten vital functions or are disfiguring, little is known
      about the endocrine consequences of this treatment. Using retrospective data, we
      examined growth velocity, changes in bone mineral density, and adrenal function
      in infants with hemangiomas treated with systemic glucocorticoids. Treatment
      consisted of oral prednisolone 2 to 4 mg/kg/day or dexamethasone 1 mg/kg/day.
      Mean growth velocity Z score on glucocorticoid therapy was -1.41 standard
      deviations in 13 patients. In four infants with adequate follow-up, growth
      velocity increased to +1.90 standard deviations after glucocorticoid treatment
      (Delta growth velocity +3.31 standard deviations). Mean lumbar spine bone mineral
      density Z score was -2.46 standard deviations before glucocorticoid treatment and
      -1.08 standard deviations at the end of treatment in six infants. Adrenal
      function after glucocorticoid therapy was assessed by low-dose
      adrenocorticotropic hormone stimulation test in 10 infants. Eight had a normal
      cortisol response, and one had a borderline response. One infant, who had been
      treated with dexamethasone, had an abnormal test result. In conclusion, systemic
      glucocorticoid treatment in infants with hemangiomas slowed linear growth, but
      "catch-up" growth was observed after treatment ceased. Glucocorticoids did not
      affect bone mineralization adversely. Only 1 of 10 glucocorticoid-treated infants
      had clear evidence of adrenal insufficiency after therapy was stopped.

PMID- 16650231
TI  - Vitiligo-like lesions and diffuse lightening of the skin in a pediatric patient
      treated with imatinib mesylate: a noninvasive colorimetric assessment.
AB  - Imatinib mesylate is a drug that has been recently approved for the treatment for
      chronic myeloid leukemia. It acts as a potent and selective inhibitor of BCR-ABL
      tyrosine kinase. It also inhibits both c-kit and platelet-derived growth factor
      receptor tyrosine kinases. Hypopigmentation of the skin in patients receiving
      this drug has been recently reported. We report a 17-year-old Caucasian patient
      affected by chronic myeloid leukemia in therapy with imatinib mesylate who
      developed hypopigmented vitiligo-like patches and generalized lightening of the
      skin. In order to evaluate the lightening observed clinically, we measured the
      progressive skin color hypopigmentation by using a colorimeter over several
      months. The colorimetric evaluation confirmed the generalized and gradual
      lightening of patient's skin over treatment with imatinib mesylate. We believe
      that this is the first reported instance of vitiligo-like lesions in a pediatric
      patient treated with imatinib mesylate, and the second in a Caucasian patient.

PMID- 16650232
TI  - Albendazole: single or combination therapy with permethrin against pediculosis
      capitis.
AB  - Pediculosis capitis is a worldwide problem and a growing concern because of
      resistance to pediculicides. In the present study, we investigated whether
      albendazole could be used in the treatment of pediculosis capitis in combination
      with 1% permethrin or alone. A total of 150 children were randomly divided to
      five groups of 30 each. Group 1 got albendazole in a single dose (400 mg), group
      2 got albendazole at 400 mg for 3 days, group 3 was given 1% permethrin, group 4
      took 1% permethrin and albendazole in a single dose (400 mg), and group 5 got 1%
      permethrin and albendazole in a dose of 400 mg for 3 days. Groups given
      albendazole were also given another 400 mg dose of albendazole after 1 week. The
      success rate of treatment at the 2-week follow-up for all groups was 61.5%,
      66.6%, 80.0%, 84.6%, and 82.1%, respectively. No statistically significant
      difference was found between the groups. The results of this study suggest that
      albendazole is effective against pediculosis capitis and there is no synergistic
      effect between albendazole and 1% permethrin.

PMID- 16650233
TI  - What syndrome is this? Barber-Say syndrome.

PMID- 16650234
TI  - Exophytic nodule on the helix.

PMID- 16650235
TI  - How to measure a growing hemangioma and assess response to therapy.

PMID- 16650237
TI  - Multiple bleeding papules in a teenager.

PMID- 16650238
TI  - Unspecified solitary peripheral T-cell lymphoma of the breast in a teenaged girl.

PMID- 16650239
TI  - Efficacy of sirolimus-eluting stents as compared to paclitaxel-eluting stents for
      saphenous vein graft intervention.
AB  - BACKGROUND: Saphenous vein graft (SVG) intervention is associated with a
      significantly increased rate of periprocedural complications and late clinical
      and angiographic restenosis. In the contemporary drug-eluting stent (DES) era,
      the comparison of the efficacy of sirolimus-eluting stents (SES) with paclitaxel
      eluting stents (PES) in SVG interventions is currently unknown. We conducted this
      retrospective analysis to investigate this issue. METHODS AND RESULTS: Forty
      seven patients with 50 SVG lesions who underwent standard percutaneous coronary
      intervention (PCI) with SES (SES group) were compared with 42 patients with 45
      SVG lesions with PES (PES group). All patients received distal protection devices
      (DPDs) during the interventions. The in-hospital, 30-day, and 6-month clinical
      outcomes in both groups were compared. Baseline clinical and procedural
      characteristics were balanced between both groups except for the proximal and mid
      lesions. There were no deaths or Q-wave myocardial infarctions (MIs) during the
      index hospitalization. Non-Q-wave MI was similar between the two groups (SES vs
      PES, 4.3% vs 7.1%, P=0.55). At 30-day and 6-month follow-ups, all the clinical
      outcomes were similar between the two groups. There was no subacute thrombosis
      (SAT) or late thrombosis in either group. The event-free survival at 6 months was
      also similar between both groups (P=0.75). CONCLUSIONS: The use of DES in
      patients undergoing SVG intervention with a DPD is clinically safe and feasible.
      As compared to SES, PES have the same efficacy and clinical outcomes in SVG
      interventions up to 6 months.

PMID- 16650240
TI  - Two-year follow-up of sirolimus-eluting stents for the treatment of proximal left
      anterior descending coronary artery stenosis.
AB  - INTRODUCTION: Sirolimus-eluting stents (SES) have demonstrated low target vessel
      revascularizations and low incidence of angiographic restenosis in several
      clinical scenarios. The aim of the present study was to assess the efficacy and
      safety of SES for the treatment of proximal left anterior descending coronary
      artery (pLAD) lesions. METHODS: Ninety-six patients with severe pLAD stenosis
      were enrolled. Angiographic and clinical follow-up were performed at 6 and 24
      months, respectively. Death, myocardial infarction (MI), new target lesion
      revascularization (TLR), and target vessel failure (TVF) were registered.
      Clinical, angiographic, and procedural variables were analyzed to identify
      predictors of restenosis. RESULTS: Mean clinical follow-up was 858+/-158 days
      (26.5+/-8.3 months). Angiographic procedural success was 100%. Angiographic
      follow-up showed 8.4% of binary restenosis without edge-restenosis phenomenon.
      Late loss was 0.15+/-0.65 mm; 15.6% of patients had an adverse cardiac event,
      with 1% of death, 5.2% of MI, 6.3% of TLR, and 9.4% of TVF. At 2 years, the
      probabilities of cumulative TVF- and TLR-free survival were 90.6% and 93.7%,
      respectively. Interestingly, no adverse cardiac events were registered between
      the first and second years. Female gender (OR 10.7 CI 95%[1.7-66.7]) and in-stent
      restenosis (OR 8.2, CI 95%[1.2-56.4]) were found as independent predictors of
      binary restenosis. Advanced chronic renal failure showed a strong trend toward
      worse outcome in terms of binary restenosis (P=0.063). CONCLUSIONS: SES for the
      treatment of pLAD stenosis proved safe and effective in a long-term follow-up
      with low incidence of adverse cardiac events and restenosis. Female gender and in
      stent restenosis were predictors of binary restenosis.

PMID- 16650241
TI  - Efficacy of rheolytic thrombectomy in early versus late myocardial infarction.
AB  - BACKGROUND: Rheolytic thrombectomy has been used successfully to treat acutely
      occluded lower-limb vessels, dialysis grafts, intrahepatic portosystemic shunts,
      and diseased native coronary vessels and saphenous vein grafts. Few studies,
      however, have examined the efficacy of rheolytic thrombectomy in the acute
      myocardial infarction (AMI) setting. We sought to determine the efficacy of the
      AngioJet Rheolytic thrombectomy catheter (Possis Medical, Minneapolis, MN, USA)
      in patients presenting with AMI either before or after 12 hours of onset of
      symptoms. METHODS: Procedural and angiographic data on 61 consecutive patients
      (January 2003-December 2003) who presented with an AMI and had rheolytic
      thrombectomy with the AngioJet catheter performed were reviewed. Coronary flow
      was assessed with thrombolysis in myocardial infarction (TIMI) frame counts
      (TFCs). Of the 61 patients studied, 40 had AngioJet performed within 12 hours and
      21 had it done after 12 hours from the onset of symptoms. Procedural success was
      measured by TFCs measured before and after the procedure and was defined as a
      change in the TFC of >or=50%. Statistical significance was considered at a P
      value of <0.05. RESULTS: Procedural success was achieved in 75% of the patients
      in the early presentation group (within 12 hours) and 0% of the patients in the
      late presentation group (after 12 hours). TFC values were statistically different
      (P<0.001) in the early group, but not significant (P>0.1) in the late
      thrombectomy group. CONCLUSION: Rheolytic thrombectomy with the AngioJet catheter
      is more effective in terms of improvement in coronary blood flow as assessed by
      TFCs when used less than 12 hours after the onset of clinical symptoms suggestive
      of AMI.

PMID- 16650242
TI  - A 5Fr catheter approach reduces patient discomfort during transradial coronary
      intervention compared with a 6Fr approach: a prospective randomized study.
AB  - Smaller guiding catheters can help reduce local complications and patient
      morbidity during transradial coronary intervention (TRI). This study was designed
      to compare the patient's morbidity, success rate, and the operator's convenience
      between 5-French (5Fr) and 6-French (6Fr) TRIs. This is a single-center
      prospective randomized study. Patients who underwent TRI, in 2003, were
      prospectively randomized to either 5Fr or 6Fr catheter groups (100 patients in
      each group). Procedure-related patient morbidity as well as clinical and
      procedural characteristics was scored and analyzed. Procedural success rate was
      not significantly different between the groups. The number of unsatisfactory
      supports (6% in 5Fr group, 3% in 6Fr group; P=0.31) and the incidence of local
      wound complications were not significantly different between the groups. Local
      wound pain scores were significantly lower in the 5Fr group compared with the 6Fr
      group, particularly during sheath insertion and removal, and during procedures.
      Pain scores were higher in female patients than in male patients during sheath
      removal (male: 1.3+/-1.3, female: 1.7+/-1.5; P=0.049). Radial artery diameter was
      well correlated with local pain score during sheath removal (r=0.31, P<0.001),
      and with the height and weight of the patients (height: r=0.33, P<0.001; weight:
      r=0.27, P<0.001). In conclusion, using a 5Fr catheter during TRI reduce, local
      access site pain, particularly in female patients with smaller body size, whereas
      the success and local complication rates were similar to a 6Fr approach.

PMID- 16650243
TI  - Usefulness of fractional flow reserve in multivessel coronary artery disease with
      intermediate lesions.
AB  - BACKGROUND: Calculation of myocardial fractional flow reserve (FFR) enables
      coronary stenoses to be evaluated. OBJECTIVES: We determined the usefulness of
      measuring the FFR in multivessel coronary artery disease, reflected in changes in
      the therapeutic options for patients with moderate coronary stenosis. METHODS: We
      studied 38 patients (30 men, 8 women; mean age: 59.8+/-10 years) with multivessel
      coronary artery disease with 41 moderate lesions. Indications for coronary
      angiography were unstable angina in 24 patients (60%), acute myocardial
      infarction in 10 (27%), and stable angina in 4 (13%). We studied the FFR (in
      nonactive lesions) in the left anterior descending artery in 23 patients (56%),
      the left coronary trunk in 8 (19.5%), the circumflex artery in 5 (12.2%), the
      right coronary artery in 3 (7.3%), and the left internal mammary artery and
      diagonal branch in 1 patient each. RESULTS: Twelve patients had a positive FFR,
      which resulted in no change in the mode of revascularization; 26 patients had a
      negative FFR, in 20 (77%) of whom the revascularization approach was changed,
      especially those with moderate lesions of the left coronary trunk or anterior
      descending artery. No differences were detected in the angiographic
      characteristics of the lesions examined. Cardiac events during follow-up were
      few. CONCLUSIONS: The results of FFR may influence the decision-making process
      after diagnostic coronary angiography in multivessel coronary artery disease with
      moderate lesions, especially in patients with a negative FFR in nonculprit
      lesions of the left trunk or left anterior descending artery.

PMID- 16650244
TI  - Intravascular ultrasound in patients with challenging in-stent restenosis:
      importance of precise stent visualization.
AB  - Intravascular ultrasound (IVUS) is widely used to optimize stent (ST)
      implantation. However, its value to guide therapy in challenging cases of in
      stent restenosis (ISR) is not well established. We present 3 patients with
      complex ISR where IVUS interrogation was useful: (a) to readily identify the ST
      "entry door," (b) to accurately detect ST malapposition, (c) to measure the
      extent of ST protrusion out from its deployed position, and (d) to guide and
      optimize therapy. Thus, due to its unique ability to visualize the complete
      structure of the underlying ST, IVUS constitutes a superb diagnostic tool in
      patients with ISR, especially in challenging anatomic settings.

PMID- 16650245
TI  - Complications of patent foramen ovale and atrial septal defect closure devices.

PMID- 16650246
TI  - Dysfunction of an atrial septal defect occluder 8 years after implantation.
AB  - Catheter interventional treatment of atrial septal defect (ASD) is widely
      accepted. The ASD occluder system (ASDOS) is no longer a widely used device
      nowadays. However, it is implanted in a substantial number of patients. We report
      a case of severe left-to-right shunt 8 years after catheter interventional
      closure of an ASD with an ASDOS device. The shunt was due to a membrane
      perforation, while the arms of the device were not dislocated. Microscopy,
      microbiology, and histology could not establish a proper explanation for the
      dysfunction; so long-term follow-up investigation may be required in patients
      with an implanted ASDOS device.

PMID- 16650247
TI  - Perforation of aortic root as secondary complication after implantation of patent
      foramen ovale occlusion device in a 31-year-old woman.
AB  - Transesophageal echocardiography (TEE) revealed a 3-mm-large patent foramen ovale
      (PFO). No other reason for these neurological events could be found and the
      patient underwent percutaneous closure of the PFO with a CARDIA Star 03/30 device
      without periprocedural complications. Four weeks later, the patient underwent a
      routine control of device without any adverse clinical symptoms. Surprisingly,
      echocardiography revealed a perforation of the aortic root by an umbrella strut
      with a small shunt from the aortic root to the right atrium. Magnetic resonance
      imaging (MRI) confirmed the diagnosis of device malposition. Consecutively, the
      patient underwent minimal invasive surgery. After removal of the single
      perforating strut, the bleeding lesion was closed. The patient remained free of
      any additional complications during the postoperative course and up until now has
      had uneventful follow-ups.

PMID- 16650248
TI  - Intravascular misplacement of an extravascular closure system: StarClose.
AB  - Closure devices for closing femoral arteries following catheterization procedures
      are routinely used. They reduce time of immobilization and decrease complications
      such as bleeding and aneurysm formation. We report of a new vascular closure
      device (StarClose, marketed by Abbott) that was misplaced in the femoral artery
      with subsequent vascular stenosis and need for surgical removal and plastic
      reconstruction.

PMID- 16650249
TI  - Development of the MAGIC congenital heart disease catheterization database for
      interventional outcome studies.
AB  - As the field of catheter-based therapies for congenital heart disease continues
      to expand, we lack the evidence-based data to make appropriate therapeutic
      decisions in the catheterization laboratory. A stumbling block to the
      determination of evidence-based therapies is our inability to simply and reliably
      share outcome data across multiple centers. We investigated whether a commonly
      used congenital heart disease catheterization database program (PedCath) could be
      used as an automatic catheterization data submission tool to a central database
      for outcome analysis. To test the feasibility of such a tool for collaborative
      outcomes research we formed a national group of seven congenital heart disease
      centers, the Mid-Atlantic Group of Interventional Cardiology, to warehouse and
      analyze catheterization data. We successfully modified PedCath to transfer the
      results of catheter-based therapies on 256 therapeutic procedures for atrial
      septal defect (ASD) closure, coarctation of the aorta angioplasty and stenting,
      and pulmonary and aortic balloon valvuloplasties over a 13-month pilot period.
      Short-term follow-up within the 13-month period was received on 31 patients. This
      study demonstrated the successful development of a simple process, requiring
      minimal data entry for investigators from around the world to share cardiac
      catheterization data for long-term outcome determination of catheter-based
      therapies for congenital heart disease.

PMID- 16650250
TI  - Spontaneous late thrombolysis of an occluded saphenous vein graft subsequent to
      acute myocardial infarction treated with percutaneous coronary intervention to
      the native culprit vessel.
AB  - A 67-year-old male with prior history of myocardial infarction and coronary
      artery bypass grafting (individual vein grafts to the left anterior descending
      artery [LAD] and right coronary artery) presented with an acute anterior ST
      elevation myocardial infarction and cardiogenic shock. The vein graft to the LAD
      was occluded with heavy thrombus burden and there was severe native CAD. Given
      the degree of thrombus burden and other anatomic considerations, percutaneous
      intervention with stenting was performed to the native proximal LAD. Three months
      later, after complaining of atypical chest pain, repeat angiogram revealed a
      spontaneous widely patent vein graft to the LAD and occluded proximal LAD.

PMID- 16650251
TI  - Transcatheter cardiovascular therapeutics annual meeting.

PMID- 16650252
TI  - FDA and industry happenings.

PMID- 16650259
TI  - Improvement in quality of life after radiofrequency ablation.

PMID- 16650260
TI  - Quality of life and cost for patients with premature ventricular contractions by
      radiofrequency catheter ablation.
AB  - OBJECTIVE: To evaluate the quality of life (QoL), health-care resource
      utilization, and cost for the patients with premature ventricular contractions
      (PVCs) by radiofrequency catheter ablation (RFCA). METHODS: RFCA was performed in
      58 patients with symptomatic PVCs that were refractory/easy to medication. A 24
      hour ambulatory electrocardiographic monitoring, QoL, health-care resources
      utilization, and cost were assessed at a screening visit and 3 and 12 months
      after RFCA. RESULTS: RFCA was successfully performed in 56 patients (96.6%). This
      resulted in a significant improvement in the QoL at 3 and 12 months after the
      procedure. There were no major complications related to the procedure. Nine
      patients (15.5%) had residual arrhythmia. Seven of them underwent repeated
      ablation with successful results. It also improved the QoL and reduced health
      care resource utilization and cost. CONCLUSIONS: RFCA is a safe and effective
      treatment for PVCs, and it is a viable alternative to drugs in the presence of
      disabling symptoms.

PMID- 16650261
TI  - A randomized clinical trial of continuous flow nitrous oxide and nalbuphine
      infusion for sedation of patients during radiofrequency atrial flutter ablation.
AB  - BACKGROUND: In patients with common atrial flutter (CAF), radiofrequency ablation
      (RFA) causes discomfort. Patients undergoing RFA often feel pain which is
      difficult to control as the mechanisms are unclear. HYPOTHESIS: Inhaled nitrous
      oxide (N2O) is a potent sedative-analgesic-anxiolytic agent that may relieve
      anxiety and discomfort during CAF ablation. METHODS AND RESULTS: In a prospective
      randomized study, the effect of Inhaled N2O was compared with that of intravenous
      sedation with Nalbuphine during CAF ablation in 76 patients (64 +/- 13 years, 56
      men). We used a 24 pole mapping catheter around the tricuspid annulus and a 8-mm
      tip ablation catheter for each patient. Forty-two patients (group 1) underwent
      radiofrequency (RF) application to the cavotricuspid isthmus 5 minutes after the
      beginning of inhalation of a (50% N2O/50% O2) mixture. Thirty-four patients
      (group 2), underwent the first RF application 15 minutes after the end of an
      infusion of Nalbuphine (20 mg delivered over 15 minutes). Ablation-related
      anxiety and discomfort were assessed using a visual analog scale (VAS) ranging
      from 0 to 100 mm, with 0 correlating to the statement "no pain at all" and 100
      with "the worst possible pain." The VAS score was determined at the end of each
      application. The number of RF applications (group 1; 10 +/- 8 vs group 2; 11 +/-
      6, P = NS) and procedure duration (group 1; 75 +/- 53 minutes vs group 2; 72 +/-
      45 minutes, P = NS), were similar for the two groups. N(2)O sedation compared
      with nalbuphine infusion reduced VAS for anxiety (10 mm +/- 8 vs 58 mm +/- 22, P
      < 0.05) and for discomfort (18 mm +/- 9 vs 45 mm +/- 34, P < 0.01), respectively.
      Although there was more frequent vomiting in group 1; 7 of 42 (17%) than in group
      2; 3 of 34 (9%), P < 0.05, patients were less likely to have hypotension during
      the procedure 1 of 42 (2.5%) versus 4 of 34 (12%), P < 0.05, respectively.
      CONCLUSION: Inhalation of a (50% N2O/50% O2) mixture during RF ablation for
      atrial flutter is a safe and efficient way to reduce anxiety and discomfort
      caused by RF applications.

PMID- 16650262
TI  - Efficacy and safety of ibutilide for the conversion of monomorphic atrial
      tachycardia.
AB  - BACKGROUND: Ibutilide is a class III antiarrhythmic drug, frequently used for
      conversion of atrial fibrillation and flutter. We studied the efficacy of
      ibutilide for acute conversion of monomorphic atrial tachycardia (monoAT) in a
      prospective, open label study in the intensive care unit of a cardiological
      clinic. METHODS: We examined 49 episodes of monoAT in 38 patients (19 men/19
      women). Thirty-three patients (87%) suffered from structural heart disease.
      Twenty-three episodes occurred while on antiarrhythmic therapy with class I or
      III drugs. Patients with prolonged QT interval (except for patients with
      pretreatment with class III drugs), hypokalemia, left ventricular failure, and
      recent myocardial infarction were excluded. All patients received one or two
      doses of 1 mg ibutilide fumarate under continuous rhythm monitoring. RESULTS:
      Conversion to sinus rhythm occurred in 19 episodes (38.8%), in 6 episodes (12.2%)
      after the first dose. Conversion rate was significantly higher in patients with a
      short history of symptoms (66.6% vs 28.6%; P < 0.05), of documented arrhythmia
      (0.13 (0/5.7) vs 2.6 (0.38/23.5) months, median (interquartile range); P < 0.03),
      higher atrial rate (272 +/- 49 vs 207 +/- 36 beats/min (means +/- SD); P <
      0.004), or without preexisting antiarrhythmic therapy (53.8% vs 21.7%; P < 0.02).
      No differences in conversion rates were found regarding gender, age, body mass
      index, left ventricular function, left atrial diameter, or underlying disease. In
      three episodes torsade de pointes occurred after ibutilide (6.1%), requiring
      defibrillation in two cases (4.1%). CONCLUSIONS: Ibutilide can be used for
      conversion of monoAT with a similar efficacy as for atrial fibrillation, but with
      a considerably lower efficacy compared to typical atrial flutter.

PMID- 16650263
TI  - "Torsade de pointes" in patients with structural heart disease and atrial
      fibrillation treated with amiodarone, beta-blockers, and digitalis.
AB  - Amiodarone is one of the most efficient and safe antiarrhythmic drugs in the
      treatment of atrial fibrillation (AF). Yet, though rare, proarrhythmic effects
      remain a clinical problem. We present three cases of amiodarone-associated
      "Torsade de pointes" tachycardia (Tdp) in patients treated concomitantly with
      heart rate controlling medication for AF. Amiodarone loading therapy was started
      for the treatment of tachyarrhythmic AF in all the three patients. All presented
      with a history of coronary heart disease, resulting in a severely reduced left
      ventricular ejection fraction in two patients. One received oral amiodarone
      loading, in the others, amiodarone was administered intravenously because of
      hemodynamically relevant AF episodes. Amiodarone therapy was combined with a
      heart rate controlling medication including a beta-blocking agent and digitalis
      in all the cases. All the subjects suffered from clinically relevant Tdp in the
      early run after initiation of amiodarone loading (max. 48 hours). The mean QTc in
      all patients before induction of Tdp was prolonged. The present case reports
      imply that amiodarone in combination with beta-blocker/digitalis therapy may be
      associated with an elevated proarrhythmic risk in selected patients with
      structural heart disease and AF.

PMID- 16650264
TI  - Blanked atrial flutter in patients with cardiac resynchronization therapy:
      clinical significance and implications for device programming.
AB  - BACKGROUND: Atrial arrhythmias are frequently observed in patients with heart
      failure and may be a primary cause for decompensation during cardiac
      resynchronization therapy (CRT). The accurate detection of organized atrial
      tachyarrhythmias poses a challenge to the function of mode-switching
      biventricular pacemakers/defibrillators. METHODS: The purpose of the study was to
      determine retrospectively the incidence of blanked atrial flutter and mode switch
      failure (2:1 lock-in), and to look for factors predisposing to this problem. A
      total number of 65 patients with CRT devices has been followed regularly over 18
      +/- 12 months. Five patients were excluded because of chronic atrial fibrillation
      and reprogramming to VVIR mode. RESULTS: Seven out of 60 patients (12%) were
      diagnosed with blanked atrial flutter at unscheduled device interrogation.
      Sustained biventricular pacing at a median rate of 125/min-mimicking sinus
      tachycardia-resulted in rapid deterioration of heart failure and hospitalization.
      Mode switch failure occurred due to coincidence of every second flutter wave with
      atrial blanking. The group with 2:1 lock-in was programmed to longer atrial
      blanking times (143 +/- 34 ms vs 105 +/- 32 ms; P = 0.026) and AV intervals (126
      +/- 8 ms vs 107 +/- 29; P = 0.001) than the group without lock-in. Other clinical
      characteristics examined did not differ between the two groups apart from a
      previous history of atrial fibrillation (P = 0.032). CONCLUSION: Blanked atrial
      flutter with rapid ventricular pacing is a clinically important problem in heart
      failure patients treated with CRT devices. Efforts should be made to avoid this
      complication by atrial lead implantation without ventricular farfield
      oversensing, by programming short PVAB and AV intervals, and by implementation of
      dedicated device algorithms.

PMID- 16650265
TI  - Medium-term efficacy of segmental ostial pulmonary vein isolation for the
      treatment of permanent and persistent atrial fibrillation.
AB  - INTRODUCTION: Previous studies suggest that segmental ostial isolation of the
      pulmonary veins for the treatment of patients with persistent and permanent
      atrial fibrillation is associated with a high rate of recurrence. Recurrence of
      atrial fibrillation is usually associated with electrical reconnection of the
      pulmonary veins to the left atrium. METHODS: We examined the efficacy of
      isolating all four pulmonary veins using an open irrigated tip ablation catheter
      and multiple procedures, to overcome the problem of electrical reconnection in
      the veins. Fifty-one patients (59 +/- 10 years, 48 male) with drug resistant and
      highly symptomatic persistent or permanent atrial fibrillation had their
      pulmonary veins electrically isolated using mapping guided segmental
      radiofrequency ablation. Atrial fibrillation had been present for 7.6 +/- 7.3
      years, and patients had failed treatment with 2.2 +/- 1.6 antiarrhythmic
      medications. Thirty-nine percent had structural heart disease. RESULTS: After a
      mean of 1.7 +/- 0.9 procedures per patient, 23 patients (45%) were in sinus
      rhythm (without cardioversion) after 16.9 +/- 9.1 months. Antiarrhythmic
      medications were required in four of those in sinus rhythm (17%). Recurrences
      were usually early (median 7 days). Neither age, duration of atrial fibrillation,
      type of atrial fibrillation, underlying heart disease, left atrial size, left
      ventricular wall thickness nor the number of failed antiarrhythmic drugs
      predicted outcomes. CONCLUSION: Persistent and permanent atrial fibrillation can
      be successfully treated using segmental isolation. However, recurrence is common
      even when all four veins are isolated using an open irrigated tip catheter, and
      multiple procedures are performed. Alternative techniques are required in this
      population.

PMID- 16650266
TI  - Evaluation of electromagnetic interference of GSM mobile phones with pacemakers
      featuring remote monitoring functions.
AB  - The aim of this study was to evaluate whether global system for mobile
      communication (GSM) cellular phones can affect the home monitoring (HM) function
      implemented in last generation pacemakers (PM). METHODS: We performed in vitro
      and in vivo tests on the BA03 PM (Biotronik GmbH, Berlin, Germany). In vitro we
      evaluated whether an improper HM procedure or an altered patient-activated HM
      function occurred. We used two cellular phone models, with a fixed external or
      internal antenna, positioned close to both the PM and the mobile phone-like
      device, during handover, ringing, and talking. All the tests were done with the
      PM in air, at 900 and 1,800 MHz GSM bands, under worst case conditions. A subset
      of these tests was repeated in 17 patients: the mobile phones were moved both
      around the PM implant site and the mobile cell phone-like device, during talking.
      RESULTS: In vitro, neither the HM procedure nor PM functioning were corrupted by
      the GSM communications: all the transmissions were correctly received, with a
      maximum transmission delay of about 110 seconds. In vivo, the rate of successful
      transmissions was 93%. CONCLUSION: Our data show that HM function does not call
      for specific restrictions on the use of GSM cellular phones.

PMID- 16650267
TI  - Pacemaker implantation as a risk factor for heart failure in young adults with
      congenital heart disease.
AB  - AIM: Complete postoperative heart block following open-heart surgery and sinus
      node dysfunction are indications for permanent cardiac pacing in children with
      congenital heart defects. The purpose of our study was to evaluate if cardiac
      pacing is a risk factor of heart failure during longtime follow-up of grown ups
      with congenital heart disease (GUCH). METHODS: For an objective assessment of
      heart failure, NT-Pro brain natriuretic peptide (BNP) and maximal oxygen uptake
      index (VO2max) during the cardiopulmonary exercise testing were measured in 346
      consecutive GUCH patients during a longtime follow-up examination. RESULTS:
      Thirty-nine of these patients who had pacemaker implantation had significantly
      increased BNP levels (448.2 +/- 76.8 vs 123.8 +/- 9.7 pg/mL, P < 0.0001) and
      significantly decreased VO(2max) (22.5 +/- 0.9 vs 27.4 +/- 0.4, P < 0.0001).
      Heart failure in pacemaker patients was associated with significantly prolonged
      QRS complex durations (171.1 +/- 8.3 ms vs 108.7 +/- 1.8 ms, P < 0.0001),
      increased right ventricular end diastolic diameters (38.7 +/- 2.1 mm vs 27.8 +/-
      0.5mm, P < 0.0001), lower heart rates at rest (69.5 +/- 1.9/min vs 82 +/- 1/min,
      P < 0.0001), and at exercise (140.3 +/- 5.8/min vs 163.5 +/- 1.2/min, P <
      0.0001). Mean fractional shortening of the left ventricle was normal in both
      patient groups. CONCLUSION: Pacemaker implantation may be associated with heart
      failure during longtime follow-up of GUCH indicated by significantly elevated BNP
      levels and decreased VO2max. Possible explanations are prolongation of QRS
      complex duration, decreased maximal heart rates during exercise, and dilatation
      of the right ventricle.

PMID- 16650268
TI  - One stage side-to-side replacement of infected pulse generators and leads.
AB  - Infected and contaminated cardiac pulse generators and leads must be removed
      entirely in order to effect a cure. We have shown through our experience with 68
      consecutive cases that explantation of the offending system and replacement of a
      new device on the opposite side can be safely accomplished in one sitting--a side
      to-side replacement--as long as there is appropriate case selection. There were
      no early or late infections of the new operative site.

PMID- 16650269
TI  - Excitation of the intrinsic conduction system through his and interventricular
      septal pacing.
AB  - BACKGROUND: Direct His bundle pacing results in rapid synchronous ventricular
      activation. However, clinical experiences with such pacing have been associated
      with long procedure times and compromised pacing and sensing performance.
      METHODS: We evaluated myocardial activation sequences (AS) for pacing of the His
      bundle and peri-His region and assessed acute pacing performance using custom
      designed plunge electrodes. Unipolar pacing was performed in isolated swine
      hearts (n = 10) using four quadripolar stimulation/sensing electrodes implanted
      into the interventricular septum and equally spaced between the membranous septum
      and the coronary sinus ostium (zones 1-4, respectively; electrode depth (ED) 1 =
      most distal, ED 4 = most proximal). Optimal pacing sites were defined as: pacing
      thresholds < or = 1.5 V, a P-R ratio of < or = 0.5, and > or = 50% occurrence of
      an intrinsic midseptal left ventricular (LV) endocardial electrical breakout (BO)
      and activation pattern. RESULTS: Pacing thresholds improved with greater depth of
      electrode location within the septum (ED 1: 1.51 +/- 0.8 V vs ED 4: 5.2 +/- 3.8
      V, P < 0.001), as did the P-R ratio (0.34 +/- 0.6 vs 0.78 +/- 1.0, P < 0.05). His
      potentials were only observed in zone 1 and 2 electrodes (0.12 and 0.02 mV,
      respectively). Only electrodes in zones 1 and 2 produced LV endocardial
      electrical BOs in the midseptal region that demonstrated an intrinsic-like
      endocardial AS. Depth 1 and 2 electrodes (11.75 and 8.75 mm, respectively) in
      zone 1 satisfied all three optimal pacing site requirements. CONCLUSIONS: This
      study has shown that LV activation patterns similar to sinus rhythm may be
      achieved without direct activation of the His bundle, while maintaining
      acceptable pacing and sensing performance. These data indicate that pacing
      systems designed to stimulate the tissues below the point at which the His bundle
      penetrates the central fibrous body may provide improved system efficiency and LV
      performance in comparison to both direct His bundle pacing and traditional pacing
      sites.

PMID- 16650270
TI  - Reduction of RV pacing by continuous optimization of the AV interval.
AB  - BACKGROUND: In patients requiring permanent pacing, preservation of intrinsic
      ventricular activation is preferred whenever possible. The Search AV+ (SAV+)
      algorithm in Medtronic EnPulsetrade mark dual-chamber pacemakers can increase
      atrioventricular (AV) intervals to 320 ms in patients with intact or intermittent
      AV conduction. This prospective, multicenter study compared the percentage of
      ventricular pacing with and without AV interval extension. METHODS: Among 197
      patients enrolled in the study, the percentage of ventricular-paced beats was
      evaluated via device diagnostics at the 1-month follow-up. Patient cohorts were
      defined by clinician assessment of conduction via a 1:1 AV conduction test at the
      2-week follow-up. The observed percentage of ventricular pacing with SAV + ON and
      the predicted percentage of ventricular pacing with SAV + OFF were determined
      from the SAV + histogram data for the period between the 2-week and 1-month
      follow-up visits. RESULTS: Of 197 patients, 110 (55.8%) had intact 1:1 AV
      conduction, of which 109 had 1-month data. SAV + remained ON in 99/109 patients;
      10 patients had intrinsic A-V conduction intervals beyond SAV + nominal and
      therefore SAV + disabled. The mean percentage of ventricular pacing in the 109
      patients was SAV+ ON = 23.1% (median 3.7%) versus SAV + OFF = 97.2% (median
      99.7%). In 87 patients without 1:1 AV conduction, SAV + was programmed OFF in 6,
      automatically disabled in 52, and remained ON in 29. In 8 of these patients, 80
      100% reduction in ventricular pacing was observed with SAV + ON. CONCLUSION: The
      Search AV+ algorithm in the EnPulse pacemaker effectively promotes intrinsic
      ventricular activation and substantially reduces unnecessary ventricular pacing.

PMID- 16650271
TI  - Back to the future: the role of the autonomic nervous system in atrial
      fibrillation.
AB  - The purpose of this manuscript is to review the current literature regarding the
      role of the autonomic nervous system (ANS) in atrial fibrillation (AF). We will
      be reviewing its effect on initiation, maintenance, and termination of AF, with
      emphasis on the role of baroreflex gain (BRG) and autonomic reflexes in the
      maintenance of this arrhythmia. While it is generally accepted that the ANS plays
      an important role in AF, the extent of that role remains controversial. Much of
      the controversy could be explained by the time frame during which the autonomic
      measurements were made, the differences in patient population, and possibly the
      differential effect of the autonomic changes on the trigger versus the substrate.
      While vagal stimulation results in shortening of the atrial effective refractory
      period and increased dispersion of refractoriness, its effect on the "trigger"
      might be antiarrhythmic. During AF, cardiac filling pressure increases while
      arterial blood pressure decreases sending conflicting messages to the medulla.
      The acute effect is an increase in sympathetic activity to ensure adequate
      hemodynamic stability. On the other hand, the long-term effects might be
      impairment in the cardiopulmonary BRG and changes that accentuate the presence of
      AF. While radiofrequency ablation has provided us with a unique insight into the
      role of possible denervation in AF suppression, the exact mechanisms involved are
      far from being completely understood. Today, in an era where great technological
      advances have occurred, our need to understand the role of the ANS in AF is
      greater than ever.

PMID- 16650272
TI  - Early detectors of the heart's electrical activity.
AB  - It was in Matteucci's rheoscopic frog in Pisa that evidence was first found for
      the electrical activity of the heart in 1844, and his results were confirmed and
      expanded 12 years later at Wurzburg. The capillary electrometer gave a continuous
      record that could be photographed, and was used initially by Einthoven who, to
      obviate the onerous mathematical conversion of the electrometer record, developed
      the string galvanometer by the close of the century, and showed its clinical
      value in 1906.

PMID- 16650273
TI  - Early left ventricular lead dislodgement related to hyperpnea respiration.
AB  - Left ventricular lead dislodgement remained a problem for cardiac
      resynchronization therapy and is one of the major causes of repeated procedures.
      We report a 30-year-old lady with possible left ventricular lead dislodgement
      related to hyperpnea respiration.

PMID- 16650274
TI  - Left ventricular lead stabilization utilizing a coronary stent.
AB  - Cardiac resynchronization therapy has been recently demonstrated to have a
      mortality and morbidity benefit in heart failure (HF) patients with cardiac
      dyssynchrony. Currently, the most widely used method of left ventricular (LV)
      lead placement involves transvenous placement of leads via the coronary sinus
      (CS) and into a tributary branch. Lead dislodgement is a common cause for
      reoperation, and continues to be a common problem despite advances in equipment
      and operator techniques. We describe a case where a coronary stent was placed in
      a lateral branch of the CS to stabilize the lead against the vessel wall.

PMID- 16650275
TI  - Uncomplicated heart and lung perforation by a displaced ventricular pacemaker
      lead: a case report.
AB  - Lead perforation is a rare complication of pacemaker implantation and associated
      with the risk of disastrous results like cardiac tamponade or pneumo-hemothorax.
      We report a patient in whom a ventricular lead perforated the right ventricle and
      left lung parenchyma without the development of cardiac tamponade, pneumothorax,
      or hemothorax. No objective evidence for perforation was found on
      echocardiographic evaluation and thorax computed tomography has made the definite
      diagnosis. In the literature available to us, it is the first reported case of an
      uncomplicated right ventricular and lung parenchymal perforation associated with
      pacemaker implantation.

PMID- 16650276
TI  - T-wave oversensing by an implantable cardioverter defibrillator after successful
      ablation of idiopathic ventricular fibrillation.
AB  - Focal ablation of trigger premature ventricular complexes (PVCs) from the
      Purkinje system helped to suppress idiopathic ventricular fibrillation (VF) in an
      athlete who had suffered from frequent appropriate shock therapies. However, only
      a few days after successful ablation T-wave oversensing occurred during exercise
      and resulted in repetitive distressing defibrillator shocks. Despite lack of any
      changes on the surface ECG, the endocardially recorded electrogram revealed an
      unfavorable ratio of R-to-T-wave amplitude predisposing to double counting with
      accelerated heart rates. This case illustrates that T-wave oversensing may
      complicate the clinical course after successful ablation of malignant Purkinje
      ectopy.

PMID- 16650277
TI  - Laser recanalization of the subclavian vein.
AB  - We report the use of a long wire and introducer as a rail for the laser
      recanalization of a chronically occluded subclavian vein following extraction of
      a fractured permanent pacing lead. This allowed new pacing leads to be placed
      through the previously occluded vessel.

PMID- 16650278
TI  - Pacemaker tachycardia in a minute ventilation rate-adaptive pacemaker induced by
      electrocardiographic monitoring.
AB  - Programmed upper rate pacing occurred in a patient with a rate-adaptive pacemaker
      when he was connected to a cardiac monitor in an emergency department. The
      tachycardia was mistakenly interpreted to be ventricular tachycardia and the
      patient received multiple DC shocks as well as intravenous amiodarone and
      sotalol, resulting in severe hemodynamic deterioration. It is important that
      physicians working in the hospital environment be familiar with this pacemaker
      monitor interaction as the problem may be easily rectified by disconnecting the
      monitor or by reprogramming the pacemaker to a nonrate-adaptive pacing mode.

PMID- 16650280
TI  - Determinants of changes in QRS duration resulting from artificial attenuation of
      ECG voltage.

PMID- 16650281
TI  - AV node ablation was impossible to perform, neither by right- nor by left-sided
      access.

PMID- 16650283
TI  - Resynchronization therapy is becoming a popular therapy for dilated
      cardiomyopathy with complete bundle blocks.

PMID- 16650284
TI  - The impact of cognitive functioning on mortality and the development of
      functional disability in older adults with diabetes: the second longitudinal
      study on aging.
AB  - BACKGROUND: For older adults without diabetes, cognitive functioning has been
      implicated as a predictor of death and functional disability for older adults and
      those with mild to severe cognitive impairment. However, little is known about
      the relationship between cognition functioning on mortality and the development
      of functional disability in late life for persons with diabetes. We examined the
      relative contribution of cognitive functioning to mortality and functional
      disability over a 2-year period in a sample of nationally representative older US
      adults with diabetes who were free from cognitive impairment through secondary
      data analyses of the Second Longitudinal Study of Aging (LSOA II). METHODS:
      Participants included 559 US adults (232 males and 327 females) >or= 70 years old
      who had diabetes and who were free from cognitive impairment were examined using
      an adapted Telephone Interview of Cognitive Status (TICS), Activities of Daily
      Living (ADL), and Instrumental Activities of Daily Living (IADL). RESULTS:
      Multivariate logistic regression was conducted to investigate the independent
      contribution of cognitive functioning to three mutually exclusive outcomes of
      death and two measures of functional disability status. The covariates included
      in the model were participants' sex, age, race, marital status, educational
      level, duration of diabetes, cardiovascular disease (CVD) status, and self-rated
      health. Persons with diabetes who had the lowest levels of cognitive functioning
      relative to the highest level of cognitive functioning had a greater odds of
      dying (AOR = 0.80, 95% CI = 0.67-0.96) or becoming disabled (AOR = 0.87, 95% CI =
      0.78-0.97) compared to those people who were disability free. CONCLUSION: Older
      adults with diabetes and low normal levels of cognition, yet within normal
      ranges, were approximately 20% more likely to die and 13% more likely to become
      disabled than those with higher levels of cognitive functioning over a 2-year
      period. Brief screening measures of cognitive functioning could be used to
      identify older adults with diabetes who are at increased risk for mortality and
      functional disability, as well as those who may benefit from interventions to
      prevent or minimize further disablement and declines in cognitive functioning.

PMID- 16650285
TI  - Aquaporin-11: a channel protein lacking apparent transport function expressed in
      brain.
AB  - BACKGROUND: The aquaporins are a family of integral membrane proteins composed of
      two subfamilies: the orthodox aquaporins, which transport only water, and the
      aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two
      recently described aquaporins, numbers 11 and 12, appear to be more distantly
      related to the other mammalian aquaporins and aquaglyceroporins. RESULTS: We
      report on the characterization of Aquaporin-11 (AQP11). AQP11 RNA and protein is
      found in multiple rat tissues, including kidney, liver, testes and brain. AQP11
      has a unique distribution in brain, appearing in Purkinje cell dendrites,
      hippocampal neurons of CA1 and CA2, and cerebral cortical neurons.
      Immunofluorescent staining of Purkinje cells indicates that AQP11 is
      intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the
      plasma membrane failed to transport water, glycerol, urea, or ions. CONCLUSION:
      AQP11 is functionally distinct from other proteins of the aquaporin superfamily
      and could represent a new aquaporin subfamily. Further studies are necessary to
      elucidate the role of AQP11 in the brain.

PMID- 16650286
TI  - Correlation between CD105 expression and postoperative recurrence and metastasis
      of hepatocellular carcinoma.
AB  - BACKGROUND: Angiogenesis is one of the mechanisms most critical to the
      postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus,
      finding the molecular markers associated with angiogenesis may help identify
      patients at increased risk for recurrence and metastasis of HCC. This study was
      designed to investigate whether CD105 or CD34 could serve as a valid prognostic
      marker in patients with HCC by determining if there is a correlation between
      CD105 or CD34 expression and postoperative recurrence or metastasis. METHODS:
      Immunohistochemical staining for the CD105, CD34 and vascular endothelial growth
      factor (VEGF) antibodies was performed in 113 HCC tissue specimens containing
      paracarcinomatous tissue and in 14 normal liver tissue specimens. The
      quantitation of microvessels identified by anti-CD105 and anti-CD34 monoclonal
      antibodies and the semiquantitation of VEGF expression identified by anti-VEGF
      monoclonal antibody were analyzed in conjunction with the clinicopathological
      characteristics of the HCC and any available follow-up information about the
      patients from whom the specimens were obtained. RESULTS: CD105 was not expressed
      in the vascular endothelial cells of any normal liver tissue or paracarcinomatous
      liver tissue but was expressed in the vascular endothelial cells of all HCC
      tissue. In contrast, CD34 was expressed in the vascular endothelial cells of
      normal liver tissue, paracarcinomatous tissue, and HCC tissue in the following
      proportions of specimens: 86.7%, 93.8%, and 100%, respectively. The microvascular
      densities (MVDs) of HCC determined by using an anti-CD105 mAb (CD105-MVD) and an
      anti-CD34 mAb (CD34-MVD), were 71.7 +/- 8.3 (SD) and 106.3 +/- 10.4 (SD),
      respectively. There was a significant correlation between CD105-MVD and CD34-MVD
      (r = 0.248, P = 0.021). Although CD34-MVD was significantly correlated with VEGF
      expression (r = 0.243, P = 0.024), CD105-MVD was more closely correlated (r =
      0.300, P= 0.005). The correlation between microscopic venous invasion and CD105
      MVD, but not CD34-MVD, was also statistically significant (r = 0.254, P = 0.018).
      Univariate analysis showed that CD105-MVD was significantly correlated with the 2
      year overall survival rate (P = 0.014); CD34-MVD was not (P = 0.601).
      Multivariate analysis confirmed that CD105-MVD was an independent prognostic
      factor and that CD34-MVD was not. CONCLUSION: The anti-CD105 mAb is an ideal
      instrument to quantify new microvessels in HCC as compared with anti-CD34 mAb.
      CD105-MVD as compared with CD34-MVD is relevant a significant and independent
      prognostic indicator for recurrence and metastasis in HCC patients.

PMID- 16650287
TI  - Mental health: a cause or consequence of injury? A population-based matched
      cohort study.
AB  - BACKGROUND: While a number of studies report high prevalence of mental health
      problems among injured people, the temporal relationship between injury and
      mental health service use has not been established. This study aimed to quantify
      this relationship using 10 years of follow-up on a population-based cohort of
      hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a
      retrospective population-based matched cohort study that utilised linked
      administrative data from Manitoba, Canada, to identify an inception cohort (1988
      1991) of hospitalised injured cases (ICD-9-CM 800-995) aged 18-64 years (n =
      21,032), which was matched to a non-injured population-based comparison group (n
      = 21,032). Pre-injury comorbidity and post-injury mental health data were
      obtained from hospital and physician claims records. Negative Binomial regression
      was used to estimate adjusted rate ratios (RRs) to measure associations between
      injury and mental health service use. RESULTS: Statistically significant
      differences in the rates of mental health service use were observed between the
      injured and non-injured, for the pre-injury year and every year of the follow-up
      period. The injured cohort had 6.56 times the rate of post-injury mental health
      hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury
      mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities
      and pre-existing mental health service use reduced the hospitalisations RR to
      3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59).
      CONCLUSION: These findings indicate the presence of pre-existing mental health
      conditions is a potential confounder when investigating injury as a risk factor
      for subsequent mental health problems. Collaboration with mental health
      professionals is important for injury prevention and care, with ongoing mental
      health support being a clearly indicated service need by injured people and their
      families. Public health policy relating to injury prevention and control needs to
      consider mental health strategies at the primary, secondary and tertiary level.

PMID- 16650289
TI  - Current applications of fibrin sealant in urologic surgery.
AB  - Biosurgical preparations designed to promote surgical hemostasis and tissue
      adhesion are being increasingly employed across all surgical disciplines. Fibrin
      sealant is the most widely studied and utilized biosurgical adjunct in urology.
      Complex reconstructive, oncologic, and laparoscopic genitourinary procedures are
      those most appropriate for sealant use. This article details the diverse urologic
      applications of fibrin sealant in the management of genitourinary injuries,
      surgery, and complications.

PMID- 16650290
TI  - Repetitive ureteral stenting for management of transplant graft ureteral
      obstruction.
AB  - PURPOSE: To review the use of repetitive stenting in the management of patients
      with ureteral obstruction after renal transplantation, with an emphasis on
      technique and functional graft outcome. MATERIALS AND METHODS: Five adult renal
      allograft recipients with ureteral obstruction were managed with repetitive
      ureteral stenting. Their hospital records, office notes, and operative reports
      were reviewed. RESULTS: All patients were successfully managed with retrograde
      ureteral stenting. They underwent an average of 8.8 stent changes over a mean
      34.5 month follow up. No decline in renal function was observed. CONCLUSIONS:
      Repetitive stenting is a viable treatment option for select patients with renal
      allograft ureteral obstruction.

PMID- 16650291
TI  - Virtual computed tomography cystoscopy in bladder pathologies.
AB  - OBJECTIVE: Assessed the usefulness of virtual cystoscopy performed with
      multidetector computed tomography (CT) in patients with different urinary bladder
      pathologies compared to the conventional cystoscopy. MATERIALS AND METHODS:
      Eighteen patients with different bladder pathologies, which consisted of 11
      tumors, 3 diverticula, 2 trabecular changes and 2 stones, were assessed with
      conventional cystoscopy and virtual CT cystoscopy. The results of virtual CT
      cystoscopy were compared with the findings of conventional cystoscopy. We
      determined the detection rate and positive predictive value of CT imaging based
      virtual cystoscopy in the diagnosis of urinary bladder lesions. RESULTS: CT
      scanning was well tolerated by all patients, and no complications occurred.
      Images in 16 (88%) of the 18 virtual cystoscopic examinations were either of
      excellent or good quality. All tumors except one, 2 trabecular changes and 2
      stones were characterized with similar findings in the both of methods. The
      masses ranged from 0.4 to 7.0 cm in diameter. While conventional cystoscopy could
      not evaluate interior part of the diverticulum, virtual CT cystoscopy could
      demonstrate clearly within it. There were no false-positive findings in our
      series. CONCLUSION: Virtual CT cystoscopy is a promising technique to be used in
      the detection of bladder lesions. It should be considered especially at the
      evaluation of bladder diverticula. In the future, it may be possible or even
      advantageous to incorporate into the imaging algorithm for evaluation of bladder
      lesion.

PMID- 16650292
TI  - A new nomogram to predict pathologic outcome following radical prostatectomy.
AB  - OBJECTIVE: To develop a preoperative nomogram to predict pathologic outcome in
      patients submitted to radical prostatectomy for clinical localized prostate
      cancer. MATERIALS AND METHODS: Nine hundred and sixty patients with clinical
      stage T1 and T2 prostate cancer were evaluated following radical prostatectomy,
      and 898 were included in the study. Following a multivariate analysis, nomograms
      were developed incorporating serum PSA, biopsy Gleason score, and percentage of
      positive biopsy cores in order to predict the risks of extraprostatic tumor
      extension, and seminal vesicle involvement. RESULTS: In univariate analysis there
      was a significant association between percentage of positive biopsy cores (p <
      0.001), serum PSA (p = 0.001) and biopsy Gleason score (p < 0.001) with
      extraprostatic tumor extension. A similar pathologic outcome was seen among
      tumors with Gleason score 7, and Gleason score 8 to 10. In multivariate analysis,
      the 3 preoperative variables showed independent significance to predict tumor
      extension. This allowed the development of nomogram-1 (using Gleason scores in 3
      categories - 2 to 6, 7 and 8 to 10) and nomogram-2 (using Gleason scores in 2
      categories - 2 to 6 and 7 to 10) to predict disease extension based on these 3
      parameters. In the validation analysis, 87% and 91.1% of the time the nomograms-1
      and 2, correctly predicted the probability of a pathological stage to within 10%
      respectively. CONCLUSION: Incorporating percent of positive biopsy cores to a
      nomogram that includes preoperative serum PSA and biopsy Gleason score, can
      accurately predict the presence of extraprostatic disease extension in patients
      with clinical localized prostate cancer.

PMID- 16650293
TI  - Are prostate carcinoma clinical stages T1c and T2 similar?
AB  - PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c
      tumors is similar to T2 tumors, indicating a need for further refinement of
      clinical staging system. To test this finding we compared clinicopathologic
      characteristics and the time to PSA progression following radical retropubic
      prostatectomy of patients with clinical stage T1c tumors to those with stage T2,
      T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive
      patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45%
      stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age,
      preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical
      margins, extraprostatic extension (pT3a), seminal vesicle invasion (pT3b), and
      time to PSA progression. Tumor extent was evaluated by a point-count method.
      RESULTS: Patients with clinical stage T1c were younger and had the lowest mean
      preoperative PSA. In the surgical specimen, they had higher frequency of Gleason
      score < 7 and more organ confined cancer. In 40.54% of the patients with clinical
      stage T2b tumors, there was extraprostatic extension (pT3a). During the study
      period, 54 patients (30.68%) developed a biochemical progression. Kaplan-Meier
      product-limit analysis revealed no significant difference in the time to PSA
      progression between men with clinical stage T1c versus clinical stage T2 (p =
      0.7959), T2a (p = 0.6060) or T2b (p = 0.2941) as well as between men with
      clinical stage T2a versus stage T2b (p = 0.0994). CONCLUSION: Clinicopathological
      features are not similar considering clinical stage T1c versus clinical stages
      T2, T2a or T2b.

PMID- 16650294
TI  - Prospective randomized controlled trial comparing three different ways of
      anesthesia in transrectal ultrasound-guided prostate biopsy.
AB  - PURPOSE: To make an objective controlled comparison of pain tolerance in
      transrectal ultrasound-guided prostatic biopsy using intrarectal topic
      anesthesia, injectable periprostatic anesthesia, or low-dose intravenous
      sedation. MATERIALS AND METHODS: One hundred and sixty patients were randomized
      into 4 groups: group I, intrarectal application of 2% lidocaine gel; group II,
      periprostatic anesthesia; group III, intravenous injection of midazolam and
      meperidine; and group IV, control, patients to whom no sedation or analgesic was
      given. Pain was evaluated using an analogue pain scale graded from 0 to 5.
      Acceptance of a repetition biopsy, the side effects of the drugs and
      complications were also evaluated. RESULTS: 18/20 (90%) and 6/20 (30%) patients
      reported strong or unbearable pain in the group submitted to conventional biopsy
      and topical anesthesia (p = 0.23, chi-square = 1.41); whereas those submitted to
      periprostatic blockade and sedation, severe pain occurred in only 2/60 (3%)
      patients (p < 0.001, chi-square = 40.19) and 3/60 (5%) patients (p < 0.001, chi
      square = 33.34). Acceptance of repetition of the biopsy was present in only 45%
      of the patients submitted to conventional biopsy, 60% of those that were given
      topical anesthesia (p = 0.52, chi-square = 0.4), compared to 100% of those
      submitted to periprostatic anesthesia (p < 0.01, chi-square = 15.17), and 95% of
      those who were sedated (p < 0.001, chi-square = 25.97%). CONCLUSIONS: Transrectal
      ultrasound-guided prostatic biopsy is an uncomfortable experience; however
      application of periprostatic blockade and intravenous analgesia are associated to
      higher tolerance of the exam and patient comfort. Low dose sedation by
      association of intravenous meperidine and midazolam is an emerging and safe
      outpatient option.

PMID- 16650295
TI  - Effect of allopurinol in chronic nonbacterial prostatitis: a double blind
      randomized clinical trial.
AB  - INTRODUCTION: The exact mechanism of chronic nonbacterial prostatitis has not
      been yet elucidated and the outcome with the current management is dismal. In
      this trial, we studied the effect of allopurinol in the treatment of this
      disease. MATERIALS AND METHODS: In this randomized double blind controlled trial,
      a calculated sample size of 56 were grouped into "intervention group" who
      received allopurinol (100 mg tds for 3 months) with ofloxacin (200 mg tds) for 3
      weeks (n = 29) and "control group" who received placebo tablets with ofloxacin (n
      = 27). Patients' scores based on the National Institute of Health Chronic
      Prostatitis Symptom Score were recorded before therapy and then every month
      during the study. A four-glass study was performed before intervention and after
      3 months. RESULTS: The 2 groups were similar regarding outcome variables. In the
      first month of study, a significant but similar improvement in symptom scores was
      observed in both groups. Microscopic examination of prostate massage and post
      massage samples were also similar in both groups. No side effects due to
      allopurinol were observed in patients. CONCLUSION: We did not find any advantage
      for allopurinol in the management of chronic prostatitis versus placebo in
      patients receiving routine antibacterial treatment.

PMID- 16650296
TI  - Cystic renal cell carcinoma arising from multilocular cystic nephroma of the same
      kidney.
AB  - Multilocular cystic nephroma is an uncommon benign entity grouped among the
      cystic non-genetic diseases. It is characterized by variable-sized, non
      communicating cysts separated by irregular thin walled septa. Though multilocular
      cystic nephroma is usually considered a benign lesion, malignant changes in the
      cysts should not be overlooked.

PMID- 16650297
TI  - Renal lymphoma. Atypical presentation of a renal tumor.
AB  - Primary renal lymphoma is a rare lesion that represents less than 1% of the
      kidney's lesions. The authors discuss the case of a 67-year-old woman with a
      renal mass identified 7 years after treatment of a non-Hodgkin's lymphoma, and
      analyze clinical and prognostic aspects of renal lymphomas. Radiological findings
      in this case showed an uncommon presentation of the renal lymphomatous lesion
      which served as a warning that tumors might appear during follow-up as atypical
      and uncommon lesions.

PMID- 16650298
TI  - Retroperitoneal migration of a self-inflicted ballpoint pen via the urethra.
AB  - Numerous accounts documenting the introduction of foreign bodies into the urinary
      bladder have been reported. These foreign bodies are typically self-inserted via
      urethral but migration from adjacent organs by an ulcerative process and
      penetrating injuries are also reported. However, ''contrary'' migration of a self
      inflicted vesical foreign body to the retroperitoneum was not previously reported
      in literature. We report here a case of a ballpoint pen self-inserted via
      urethral by a female patient, which was identified in retroperitoneal position
      years later.

PMID- 16650299
TI  - Refining the laparoscopic retroperitoneal lymph node dissection for testicular
      cancer.
AB  - Since its initial description, the laparoscopic retroperitoneal lymph node
      dissection has evolved considerably, from a purely diagnostic tool performed to
      stage germ cell testicular cancer to a therapeutic operation that fully
      duplicates the open technique. Herein, we describe the current technique employed
      at our institution, along with illustrations of all surgical steps, and delineate
      the refinements of the technique over time.

PMID- 16650300
TI  - Ectopic adrenal tissue in the spermatic cord in pediatric patients: surgical
      implications.
AB  - OBJECTIVE: To study the incidence and relevance of ectopic adrenal tissue in
      pediatric patients who underwent groin surgical explorations. MATERIALS AND
      METHODS: We studied 1120 patients with groin surgical explorations during a
      period of 8 consecutive years. Patients' clinical data and histological findings
      were analyzed. RESULTS: We found ectopic adrenal tissue in 13 patients in 1120
      groin surgical exploration (1.16%). Of the 13 cases, 5 were diagnosed as having
      undescended testes, 6 inguinal hernia and 2 communicating hydrocele. Median age
      at diagnosis was 5.6 years. Histological sections showed adrenal cortical tissue
      with no medulla present. CONCLUSION: Based on the clinical implications of those
      adrenal rests it is mandatory the removal of this ectopic tissue whenever
      encountered during surgical interventions in the groin region in children.

PMID- 16650301
TI  - Unilateral renal agenesia associated with partial epididymis and vas deferens
      agenesia in a patient with abdominal testicle.
AB  - This study considers a unilateral renal agenesia associated with agenesia of the
      epididymis body and tail and the vas deferens and non-palpable left testicle in a
      20-month-year-old patient. During laparoscopic procedure, the testicle was
      positioned at approximately 5 cm above the inguinal ring. The size was
      appropriate for the age and the head of the epididymis was situated in its normal
      position. The decision was made to perform the first step of the Fowler-Stephens'
      surgery and the patient presented a good evolution. The association of male duct
      system agenesia with unilateral renal agenesia in a patient with cryptorchidism
      diagnosed by laparoscopy is an extremely rare event, however generally in these
      cases the testicle is of normal size, presents unaltered hormonal function, and
      must be preserved.

PMID- 16650302
TI  - Bladder drainage and glandular epithelial morphometry of the prostate in benign
      prostatic hyperplasia with severe symptoms.
AB  - OBJECTIVE: Morphometrically analyze the cells nuclei of the basal layer of the
      prostatic glandular epithelium in 20 patients aged between 57 and 85 years
      presenting benign prostatic hyperplasia with severe symptoms, catheterized or
      not. MATERIALS AND METHODS: Patients with score of severe prostatic symptoms
      (with indication for transurethral resection of the prostate) were distributed
      according to the presence or absence of bladder drainage previous to the surgery,
      in the treated group (n = 10, catheter during 3 months) and in the control group
      (n = 10, without catheter). After obtaining prostate fragments through
      transurethral resection and the use of morphometric techniques, 100 nuclei of
      prostatic glands epithelium cells were studied (as to size and form), and
      compared to 500 nuclei from patients submitted to catheter drainage and 500
      nuclei of non-catheterized patients. RESULTS: Significantly reduced values of the
      major, medium and minor nuclear diameters, volume, area and perimeter, contour
      index and nuclear volume-nuclear area ratio were observed in the treated group in
      relation to the control group. As to the form, eccentricity and coefficient of
      nuclear form, there were significant differences between treated and control
      groups. CONCLUSION: Long-term catheter bladder drainage in patients presenting
      benign prostatic hyperplasia with severe symptoms is associated to the reduction
      of morphometric parameters of the nuclei of prostatic glands' epithelial cells,
      suggesting a likely decompressive duct effect.

PMID- 16650303
TI  - Interference of enalaprilat on glomerular permeability to macromolecules (IgG) in
      acute unilateral ureteral obstruction in rats.
AB  - INTRODUCTION: Unilateral ureteral obstruction breaks out events that cause the
      transitory increase of glomerular permeability to macromolecules, both in the
      obstructed kidney and in the contralateral kidney, suggesting the presence of
      some factor, with a systemic action, liberated as a response to the obstruction.
      We know that the rennin-angiotensin system is activated by acute ureteral
      obstruction. We have developed an experiment to assess the role of angiotensin II
      on the glomerular permeability to IgG due to acute ureteral obstruction, using
      enalaprilat, an angiotensin enzyme conversion inhibitor, to block the effects of
      the activation of the rennin-angiotensin system. MATERIALS AND METHODS: We have
      used 45 adult Wistar female rats, distributed into 3 main groups: a control group
      with 5 animals and 2 experiment groups each one with 10 animals submitted to
      unilateral ureteral obstruction and nephrectomy at 60 and 120 minutes. Each
      experiment group had its simulation correspondent (sham). We have studied both
      kidneys through the direct immunofluorescence method. RESULTS: We have found
      positive permeation in animals without enalaprilat in both kidneys and negative
      permeation in those in which the drug was used. CONCLUSION: We have concluded
      that enalaprilat interferes in this alteration of permeability, suggesting that
      angiotensin II is involved in the loss of selectivity of the glomerular membrane.

PMID- 16650304
TI  - Histological and histochemical changes of the intestinal mucosa at the urothelial
      enteric anastomotic site.
AB  - OBJECTIVE: The incorporation of bowel segments for urinary tract reconstruction
      may induce intestinal mucosal changes with the development of metabolic,
      nutritional, gastrointestinal and carcinogenic complications. The early
      histological and histochemical changes of the intestinal mucosa in contact with
      the feces-urine mixture, are evaluated in the present study. MATERIALS AND
      METHODS: Twelve rats (operated group) were submitted to a vesico-colonic
      anastomosis, and 10 rats (control group) underwent a sham operation (the colon
      was opened and immediately sutured). On the operated group, the left colon was
      divided into 3 equal portions and the middle segment was used for the bladder
      colonic anastomosis. After 20 weeks, the animals were sacrificed and the entire
      left colon in each group, as well as the bladder and the vesico-colonic
      anastomosis in the operated group, was removed. The proximal, middle (anastomotic
      site in the operated group and sutured portion in the control group) and distal
      colon were used for histological and histochemical studies. RESULTS: Metaplasia,
      chronic inflammatory process and fibrosis were significantly greater at the
      anastomotic site compared to the middle segment of the control group. There were
      no differences in both groups in terms of dysplasia, atrophy and hypertrophy
      either on the proximal, middle or anastomotic area and distal portion of the left
      colon. All animals in the operated group showed a reduced presence of sulfomucin
      and an increase in the sialomucin content. CONCLUSION: The histological changes
      observed in this study may suggest a precancerous phenomenon.

PMID- 16650326
TI  - Interpreting serological surveys using mixture models: the seroepidemiology of
      measles, mumps and rubella in England and Wales at the beginning of the 21st
      century.
AB  - A mixture modelling technique is applied to age-specific frequency distributions
      of quantitative results from serological surveys for measles, mumps and rubella
      using samples collected across the age range in England and Wales in 2000. In
      accordance with previous studies the analysis suggests that the antibody response
      to natural infection is stronger than that produced by vaccination, that vaccine
      induced antibody levels wane with time and that levels of vaccine-induced
      antibody response vary for each virus infection being strongest for rubella and
      weakest for mumps. The current mumps epidemic in the United Kingdom is focused in
      cohorts born during 1982-1987 who were too old to have received routine MMR
      vaccination. In the cohort born in 1981-1985 the model estimates that 7.5% have
      no evidence of mumps specific IgG and 24.9% have the lowest level of detectable
      antibody. The similar proportions of mumps antibody in these categories among
      cohorts with opportunity for 1 or 2 doses of vaccine is a concern, as the degree
      to which these individuals are protected is unclear. Investigations into the
      efficacy of two doses of a mumps containing vaccine should be a priority during
      the current epidemic.

PMID- 16650327
TI  - Antimicrobial susceptibility and serotype distribution of Streptococcus
      pneumoniae isolated from patients with community-acquired pneumonia and molecular
      analysis of multidrug-resistant serotype 19F and 23F strains in Japan.
AB  - A nationwide study was undertaken to determine the susceptibility to penicillin
      and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated
      from 114 adult patients with community-acquired pneumonia over 22 months at 20
      hospitals and medical centres in different regions in Japan. All but five
      isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40
      (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%)
      were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were
      susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and
      vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and
      azithromycin; only two were resistant to levofloxacin. Differences were found in
      the distribution of serotypes among isolates showing susceptibility to penicillin
      (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and
      23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25
      strains of serotype 19F had a single DNA profile, pattern A, a pattern closely
      similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A
      strains were not susceptible to penicillin but carried the macrolide resistance
      gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous
      but six were highly similar (pattern b) yet distinct from the Spanish multidrug
      resistant 23F clone although possibly related to the Taiwan multidrug-resistant
      23F clone. The pattern b strains were not susceptible to penicillin and also
      harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant
      pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the
      pandemic multidrug-resistant serotypes should be intensified.

PMID- 16650328
TI  - High case-fatality rates of meningococcal disease in Western Norway caused by
      serogroup C strains belonging to both sequence type (ST)-32 and ST-11 complexes,
      1985-2002.
AB  - A total of 293 meningococcal disease (McD) patients from Western Norway
      hospitalized during 1985-2002 were examined for risk factors related to death.
      The case-fatality rate (CFR) increased from 4% during 1985-1993 to 17% during
      1994-2002. We analysed the phenotypic and genotypic characteristics of the
      meningococcal patient isolates, with the aim of identifying whether highly
      virulent meningococcal strains contributed to the increased CFR. The Norwegian
      epidemic strain B:15:P1.7,16/ST-32 complex was overall the most common
      phenotype/genotype (n=75) and caused most deaths (n=9; CFR 12.0%). However,
      fatality was significantly associated with disease caused by serogroup C
      meningococcal strains; C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains, which
      had the highest CFRs of 21.1% and 18.2% respectively. Serogroup B strains of the
      ST-32 complex differing by serotype and/or serosubtype from the epidemic strain
      had a CFR of 5.1%, while the CFR of disease caused by other strains (all
      phenotypes and genotypes pooled) was 2.2%. The distribution of phenotypes/clonal
      complexes varied significantly between 1985-1993 and 1994-2002 (P<0.001); B:15/ST
      32 complex strains decreased whereas both C:15:P1.7,16/ST-32 complex strains and
      strains with other phenotypes/clonal complexes increased. Our results indicate
      that C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains were highly virulent
      strains and contributed to the high CFR of McD in patients from Western Norway.
      To reduce fatality, rapid identification of such virulent strains is necessary.
      In addition, early and specific measures should include public information,
      vaccination of populations at risk of disease and carriage eradication, when
      clustering of patients occurs.

PMID- 16650329
TI  - Outbreak of hepatitis A in two federal states of Germany: bakery products as
      vehicle of infection.
AB  - In April 2004, increased numbers of hepatitis A were noted in six neighbouring
      districts in Germany. Exploratory interviews showed that patients had consumed
      bakery products from company X where two employees had been diagnosed with
      hepatitis A in February. A case-control study of consumption of products of
      company X was carried out through telephone interviews. Altogether, 64 cases were
      identified. Fifty-two cases and 112 controls aged >or=16 years were included in
      the case-control study. In total, 46/52 cases and 37/112 controls had consumed
      company X products [odds ratio (OR) 15.5, 95% confidence interval (CI) 6.1-39.7].
      Of these, 36/46 cases and 16/37 controls had consumed pastries (OR 4.7, 95% CI
      1.8-12.3), 25/46 cases and 12/37 controls had consumed filled doughnuts (OR 2.5,
      95% CI 1.0-6.1). Sequence analysis of the VP1-2A junction region indicated 100%
      strain homology between cases and an infected employee of company X. We
      recommended reinforcement of hygiene precautions, and consideration of a
      prolongation of compulsory work absence after post-exposure vaccination.

PMID- 16650330
TI  - A new Puumala hantavirus subtype in rodents associated with an outbreak of
      Nephropathia epidemica in South-East Germany in 2004.
AB  - A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East
      Germany, starting in April 2004. While only three cases were registered from 2001
      to 2003, a dramatically increased number of clinically apparent human hantavirus
      infections (n=38) was observed in 2004, plus seven additional cases by June 2005.
      To determine the reservoir responsible for the infections, a total of 43 rodents
      were trapped in Lower Bavaria. Serological and genetic investigations revealed
      that Puumala virus (PUUV) is dominant in the local population of bank voles.
      Partial PUUV S segment nucleotide sequences originating from bank voles at four
      different trapping sites in Lower Bavaria showed a low divergence (up to 3.1%).
      This is contrasted by a nucleotide sequence divergence of 14-16% to PUUV strains
      detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences
      from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be
      responsible for the observed increase of human hantavirus infections in 2004
      2005.

PMID- 16650331
TI  - The paediatric burden of rotavirus disease in Europe.
AB  - Rotaviruses are a major cause of hospitalizations for acute gastroenteritis in
      developed countries. This review shows the burden of rotavirus disease in < 5
      year-old children in Europe. An estimated 72,000-77,000 hospitalizations for
      community-acquired rotavirus disease occur annually in the 23 million under-fives
      living in the European Union (EU-25), with a median cost of Euro 1417 per case.
      Annual hospitalization incidence rates range from 0.3 to 11.9/1000 children < 5
      years old (median 3/1000). The median proportion of hospital-acquired rotavirus
      disease among all cases of hospitalization for rotavirus disease is estimated to
      be 21%. Countries of the EU-25 require information on the burden of rotavirus
      disease to support introduction of rotavirus vaccines. Data on cases treated at
      home, medical visits, and emergency wards as well as rotavirus-associated deaths
      are limited. To fully evaluate the impact and effectiveness of rotavirus
      vaccination programmes in Europe, additional epidemiological studies will be
      critical and desirable.

PMID- 16650332
TI  - Survival characteristics of Salmonella enterica serovar Enteritidis in chicken
      egg albumen.
AB  - Salmonella enterica serovar Enteritidis (SE) is a major foodborne pathogen
      primarily causing human infection through contaminated chicken eggs. To
      understand how SE survives in chicken egg albumen, we systematically and
      quantitatively analysed the survival properties of SE in egg albumen and
      identified factors affecting its survival. Survival assays of SE in egg indicate
      that egg albumen restricted the growth of SE. A major factor that controlled SE's
      growth in egg albumen was iron restriction, since egg albumen supplemented with
      iron allowed SE to grow, and iron acquisition mutants of SE showed decreased
      survival in egg albumen. In addition, low pH of albumen, high concentrations of
      bacteria and low incubation temperatures of bacteria with albumen facilitates the
      survival of SE. Our results suggest that egg albumen uses multiple mechanisms to
      control SE including iron limitation, surface interaction and possible enzymatic
      activities.

PMID- 16650333
TI  - Evaluation of standardized scored inspections for Legionnaires' disease
      prevention, during the Athens 2004 Olympics.
AB  - The study was designed to determine the contribution of standardized scored
      inspections implemented during the Athens 2004 Pre-Olympic and Olympic period, in
      assessing the presence of Legionella spp. in water sites. Inspection grading
      scores of 477 water supply systems, 127 cooling towers and 134 decorative
      fountains were associated with the corresponding microbiological test results of
      2514 samples for Legionella spp. Nine violations of water supply systems and nine
      of cooling towers significantly associated with positive microbiological test
      results, and four violations of water supply systems and one of cooling towers
      were among those designated as 'critical' water safety hazards in the inspection
      reports. The study documents a strong correlation [water supply systems (RR
      1.92), cooling towers (RR 1.94)] between unsatisfactory inspection scoring
      results and Legionella-positive microbiological test results (in excess of 10,000
      c.f.u./l) and suggests the utility of inspection scoring systems in predicting
      Legionella proliferation of water systems and in preventing Legionnaires'
      disease.

PMID- 16650334
TI  - Biochemical fingerprinting of Vibrio parahaemolyticus by the PhenePlate system:
      comparison between pandemic and non-pandemic serotypes.
AB  - During recent years a pandemic clone of Vibrio parahaemolyticus has emerged.
      Isolates of this clone are distributed among several serotypes, but are
      genotypically related. In the present study, a phenotyping method (biochemical
      fingerprinting) was used to characterize pandemic and non-pandemic isolates
      belonging to V. parahaemolyticus. It was found that the pandemic isolates showed
      a high level of phenotypic homogeneity and a majority of the pandemic isolates
      belonged to the same biochemical phenotype, whereas non-pandemic V.
      parahemolyticus isolates were more heterogeneous. In conclusion, biochemical
      fingerprinting of V. parahaemolyticus can be used as a first screening method to
      differentiate between pandemic and non-pandemic isolates of V. parahaemolyticus.

PMID- 16650335
TI  - Abstracts of EUROANAESTHESIA 2006: Annual Meeting of the European Society of
      Anaesthesiology. Madrid, Spain. June 3-6, 2006.

PMID- 16650336
TI  - Disarray of sarcomeric alpha-actinin in cardiomyocytes infected by Trypanosoma
      cruzi.
AB  - Infection with Trypanosoma cruzi causes acute myocarditis and chronic
      cardiomyopathy. Remarkable changes have been demonstrated in the structure and
      physiology of cardiomyocytes during infection by this parasite that may
      contribute to the cardiac dysfunction observed in Chagas' disease. We have
      investigated the expression of alpha-actinin, an actin-binding protein that plays
      a key role in the formation and maintenance of Z-lines, during the T. cruzi
      cardiomyocyte interaction in vitro. Immunolocalization of alpha-actinin in
      control cardiomyocytes demonstrated a typical periodicity in the Z line of
      cardiac myofibrils, as well as its distribution at focal adhesion sites and along
      the cell-cell junctions. No significant changes were observed in the localization
      of alpha-actinin after 24 h of infection. In contrast, depletion of sarcomeric
      distribution of alpha-actinin occurred after 72 h in T. cruzi-infected
      cardiomyocytes, while no change occurred at focal adhesion contacts. Biochemical
      assays demonstrated a reduction of 46% and 32% in the expression of alpha-actinin
      after 24 h and 72 h of infection, respectively. Intracellular parasites were also
      stained with an anti-alpha-actinin antibody that recognized a protein of 78 kDa
      by Western blot. Taken together, our data demonstrate a degeneration of the
      myofibrils in cardiomyocytes induced by T. cruzi infection, rather than a
      disassembly of the I bands within sarcomeres.

PMID- 16650337
TI  - Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface
      tegumental responses to in vitro treatment with the sulphoxide metabolite of the
      experimental fasciolicide compound alpha.
AB  - Mature Fasciola hepatica of the triclabendazole-resistant Sligo isolate were
      incubated in vitro with 10 microg/ml of the sulphoxide metabolite of compound
      alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-H-benzimidazole]; the metabolite
      will be referred to as alpha.SO. Changes resulting from drug treatment were
      examined by scanning electron microscopy (SEM), transmission electron microscopy
      (TEM) and tubulin immunocytochemistry (ICC). SEM revealed that disruption to the
      tegumental surface mainly took the form of swelling and blebbing. Extensive spine
      loss occurred on the ventral surface of the oral cone, and sloughing of the
      tegument was observed along the lateral margins of the fluke. Examination of
      sections from the anterior mid-body region at the TEM level revealed that
      treatment with alpha.SO led to swelling of the basal infolds and mitochondria
      within the tegumental syncytium; also, accumulations of secretory bodies beneath
      the apical plasma membrane. The tegumental cell bodies contained swollen
      mitochondria and cisternae of granular endoplasmic reticulum, but few Golgi
      complexes were observed. An increase in T2 secretory bodies was observed, whilst
      in the T1 tegumental cells, the T1 secretory bodies had decreased in number.
      Immunocytochemical (ICC) studies showed that incubation with alpha.SO, ABZ.SO and
      TCBZ.SO did not cause significant changes to the distribution of tubulin within
      the tegumental syncytium of the Sligo isolate. In contrast, alpha.SO, ABZ.SO and
      TCBZ.SO caused severe disruption to tubulin organization within the syncytial
      layer of the TCBZ-susceptible Cullompton isolate. The EM results confirm that
      compound alpha is a fasciolicide capable of disrupting the tegument of mature
      TCBZ-resistant F. hepatica; however, this was not accompanied by any change in
      tubulin immunoreactivity.

PMID- 16650338
TI  - Ecological divergence of closely related Diplostomum (Trematoda) parasites.
AB  - Parasite life-cycles present intriguing model systems to study divergence in
      resource use and ecology between parasite taxa. In ecologically similar taxa,
      consistent selective forces may lead to convergence of life-history traits, but
      resource overlap and similarity of life-cycles may also promote divergence
      between the taxa in (1) use of host species or (2) specific niche within a host.
      We studied the life-history characteristics of 2 sympatric species of Diplostomum
      parasites, D. spathaceum and D. gasterostei, concentrating particularly on
      differences in intermediate host use and characteristics of the infective stages
      between the species. This group of trematodes is a notoriously difficult
      challenge for morphological taxonomy and therefore any information on the ecology
      of these species can also be helpful in resolving their taxonomy. We observed
      that these species indeed had diverged as they used mainly different snail and
      fish species as intermediate hosts and in controlled experiments infected
      different regions of the eye (lens and vitreous body) of a novel fish host.
      Interestingly, cercarial characteristics (activity and life-span) were similar
      between the species and the species were difficult to separate at the cercarial
      stage unless one observes their swimming behaviour. The release of cercaria from
      the snail hosts was higher in D. spathaceum, but when cercarial numbers were
      proportioned to the volume of the snail host, the production was higher in D.
      gasterostei suggesting differences in the rate of snail host exploitation between
      the parasite species. These results corroborate the prediction that closely
      related parasite taxa which are competing for the same resources should have
      diverged in their life-history characteristics and host use.

PMID- 16650339
TI  - The taxonomic and phylogenetic relationships of Trypanosoma vivax from South
      America and Africa.
AB  - The taxonomic and phylogenetic relationships of Trypanosoma vivax are
      controversial. It is generally suggested that South American, and East and West
      African isolates could be classified as subspecies or species allied to T. vivax.
      This is the first phylogenetic study to compare South American isolates (Brazil
      and Venezuela) with West/East African T. vivax isolates. Phylogeny using
      ribosomal sequences positioned all T. vivax isolates tightly together on the
      periphery of the clade containing all Salivarian trypanosomes. The same branching
      of isolates within T. vivax clade was observed in all inferred phylogenies using
      different data sets of sequences (SSU, SSU plus 5.8S or whole ITS rDNA). T. vivax
      from Brazil, Venezuela and West Africa (Nigeria) were closely related
      corroborating the West African origin of South American T. vivax, whereas a large
      genetic distance separated these isolates from the East African isolate (Kenya)
      analysed. Brazilian isolates from cattle asymptomatic or showing distinct
      pathology were highly homogeneous. This study did not disclose significant
      polymorphism to separate West African and South American isolates into different
      species/subspecies and indicate that the complexity of T. vivax in Africa and of
      the whole subgenus Trypanosoma (Duttonella) might be higher than previously
      believed.

PMID- 16650340
TI  - Identification and characterization of an asparaginyl proteinase (legumain) from
      the parasitic nematode, Haemonchus contortus.
AB  - Asparaginyl proteinases (or legumains) are a recently identified, novel class of
      cysteine proteinase which specifically hydrolyse peptide bonds after asparagine
      residues. Legumains have been implicated in the activation of cysteine proteases,
      particularly cathepsin B-like proteinases which are thought to help degrade the
      bloodmeal in blood-feeding helminths such as schistosomes, hookworms and other
      nematode species. An EST sequence representing a full-length legumain was
      identified from the Haemonchus contortus dataset. This encoded a protein with a
      predicted Mr of 49 kDa, the amino acid sequence of which showed good homology (34
      40% identity) to legumains from Schistosoma mansoni, human and rat and contained
      a legumain-like active site. RT-PCR indicated that the legumain transcript was
      expressed from the L4 life-cycle stage onwards. The coding sequence was expressed
      in E. coli and antibodies to the resultant recombinant protein indicated that the
      enzyme was expressed in the microvillar surface of the intestinal cells. Legumain
      activity was detected in extracts of the adult parasite but not the host
      protective Thiol-Sepharose-binding fraction, although it was detectable in the
      latter by immunoblot. Activity was relatively insensitive to E64, an inhibitor of
      cysteine proteinases and completely inhibited by the alkylating agent, N
      ethylmaleimide, consistent with inhibitor effects on previously characterized
      legumains.

PMID- 16650341
TI  - In severely suicidal young adults, hopelessness, depressive symptoms, and
      suicidal ideation constitute a single syndrome.
AB  - BACKGROUND: Despite voluminous research on the role of hopelessness and
      depression in suicidality, a systematic examination of various causal models
      pertaining to these variables is conspicuous in its absence. METHOD: The
      directions of relationships between the three variables were examined by means of
      a prospective-longitudinal, cross-lagged, three-wave design in a severely
      suicidal young adults. RESULTS: Structural Equation Modeling (SEM) analyses
      revealed synchronous, but not longitudinal, associations between hopelessness,
      depressive symptoms, and suicidal ideation. CONCLUSIONS: In severely suicidal
      young adults, the three clinical constructs appear to constitute a single
      depressive syndrome.

PMID- 16650342
TI  - Sex differences in subclinical and DSM-IV pathological gambling: results from the
      National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: To examine sex differences in DSM-IV subclinical and pathological
      gambling in nationally representative data of the US population. METHOD: Data
      come from a large (n = 43093) representative sample of the adult US population.
      RESULTS: The lifetime prevalence rate of DSM-IV pathological gambling was 0.64%
      (95% CI 0.50-0.78) for men and 0.23% (95% CI 0.17-0.29) for women, whereas the
      lifetime prevalence of subclinical pathological gambling was 6.79% (95% CI 6.32
      7.26) for men and 3.26% (95% CI 2.93-3.59) for women. For subclinical
      pathological gambling, men were significantly (p < 0.01) more likely than women
      to have smoked more than two packs of cigarettes a day, to be classified as heavy
      drinkers and to have lifetime diagnoses of alcohol and drug use disorders. Women
      with subclinical and pathological gambling were significantly more likely than
      men to have lifetime mood and anxiety disorders. With respect to pathological
      gambling, women had later ages of onset of the disorder, and were significantly
      more likely than men to report gambling to relieve depressed mood and to prefer
      casino gambling. Rates of treatment-seeking for DSM-IV pathological gambling were
      low for both men and women. CONCLUSIONS: There are important sex differences in
      the prevalence, symptom pattern, sociodemographic and clinical correlates and
      course of DSM-IV subclinical and pathological gambling. Results underscore the
      need to investigate sex differences in the social determinants, neurobiology and
      treatment response of DSM-IV subclinical and pathological gambling.

PMID- 16650343
TI  - Brain reserve and cognitive decline: a non-parametric systematic review.
AB  - BACKGROUND: A previous companion paper to this report (Valenzuela and Sachdev,
      Psychological Medicine 2006, 36, 441-454) suggests a link between behavioural
      brain reserve and incident dementia; however, the issues of covariate control and
      ascertainment bias were not directly addressed. Our aim was to quantitatively
      review an independent set of longitudinal studies of cognitive change in order to
      clarify these factors. METHOD: Cohort studies of the effects of education,
      occupation, and mental activities on cognitive decline were of interest.
      Abstracts were identified in MEDLINE (1966-September 2004), CURRENT CONTENTS (to
      September 2004), PsychINFO (1984-September 2004), Cochrane Library Databases and
      reference lists from relevant articles. Eighteen studies met inclusion criteria.
      Key information was extracted by both reviewers onto a standard template with a
      high level of agreement. Cognitive decline studies were integrated using a non
      parametric method after converting outcome data onto a common effect size metric.
      RESULTS: Higher behavioural brain reserve was related to decreased longitudinal
      cognitive decline after control for covariates in source studies (phi=1.70,
      p<0.001). This effect was robust to correction for both multiple predictors and
      multiple outcome measures and was the result of integrating data derived from
      more than 47000 individuals. CONCLUSIONS: This study affirms that the link
      between behavioural brain reserve and incident dementia is most likely due to
      fundamentally different cognitive trajectories rather than confound factors.

PMID- 16650344
TI  - Race/ethnic differences in the prevalence and co-occurrence of substance use
      disorders and independent mood and anxiety disorders: Results from the National
      Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: Very few large national epidemiologic surveys have examined the
      prevalence of psychiatric disorders among Asians and Native Americans due to
      small sample sizes. Very little is also known about the co-occurrences between
      substance use disorders and mood and anxiety disorders among these two minority
      groups and how their rates compare to Whites, Blacks, and Hispanics. METHOD:
      Analyses were based on a large (n = 43093) nationally representative survey of
      the adult (18+ years), U.S. population supplemented by a group quarters sampling
      frame. Prevalences and associations of major DSM-IV mood, anxiety and substance
      use disorders were examined among all major race/ethnic subgroups of the
      population. RESULTS: Twelve-month rates of most mood, anxiety and substance use
      disorders were generally greatest among Native Americans and lowest among Asians.
      For most race/ethnic subgroups, alcohol and drug dependence, but not abuse, were
      significantly associated with mood disorders. With few exceptions, there were no
      significant associations between alcohol and drug abuse and anxiety disorders. In
      contrast, alcohol dependence was associated with most anxiety disorders among
      Whites, Blacks and Asians, but not among Native Americans. CONCLUSIONS: The 12
      month prevalence of substance use, mood, and anxiety disorders varied greatly
      across the five major race/ethnic subgroups of the population. Twelve-month co
      occurrence of substance use disorders and mood and anxiety disorders was
      pervasive among all race/ethnic subgroups. Future research is also needed to
      understand race/ethnic differentials in prevalence and co-occurrence of these
      disorders with a particular focus on factors that may give rise to them.

PMID- 16650345
TI  - Low prevalence of depression and anxiety is linked to statutory retirement ages
      rather than personal work exit: a national survey.
AB  - BACKGROUND: Common mental disorder prevalence decreases substantially around the
      conventional retirement age for men in the UK, but trends for older women are
      more continuous. Prevalence changes in depression and anxiety around retirement
      are less clear, as is the role of risk factors. The aim of this study was to
      establish whether work status, age or other known risk factors account for the
      reduced prevalence of depressive episode and anxiety disorder around retirement
      ages for men and for women. METHOD: The British Psychiatric Morbidity Survey
      (BPMS) 2000 was analysed, including 1875 men and 2253 women aged 45-75 years.
      Diagnoses were from the Revised Clinical Interview Schedule (CIS-R). Logistic
      models were adjusted for sociodemographic factors, social network, work status,
      life events, physical illness and disability. RESULTS: There are marked
      reductions in the prevalence of depressive episode after 60 years for women [60%
      lower prevalence, 95% confidence interval (CI) 40-80] and 65 years for men (90%
      lower prevalence, 95% CI 70-100), compared to the youngest age groups. For
      anxiety disorder, the reduction in prevalence was 80% (95% CI 60-90) for men and
      40% (95% CI 20-60) for women. In fully adjusted multivariate models, the strong
      association between diagnoses and age groups remained, for both genders. Work
      status was a significant factor for men but not for women. CONCLUSION: There is a
      discontinuity in the prevalence of depressive episode for both men and women,
      coinciding with statutory retirement ages. No studied risk factor reduced the
      associations between age group and disorders. This population scale recovery may
      provide a model for understanding non-genetic factors.

PMID- 16650346
TI  - Illicit psychoactive substance use, abuse and dependence in a population-based
      sample of Norwegian twins.
AB  - BACKGROUND: Prior population-based twin studies from two Anglophonic countries
      with relatively high rates of drug use - the USA and Australia - suggest that
      genetic factors contribute substantially to individual differences in the use,
      abuse and dependence of illicit psychoactive substances. Would these results
      replicate in Norway, a Nordic country with a low prevalence of illicit drug use?
      METHOD: Lifetime use, abuse and dependence of five illicit drug categories
      (cannabis, stimulants, opiates, cocaine and psychedelics) were assessed at
      personal interview in 1386 complete young adult twin pairs ascertained from the
      Norwegian Institute of Public Health Twin Panel. Twin model fitting was performed
      using the Mx statistical package on three phenotypes: any lifetime use,
      endorsement of at least one DSM-IV symptom of abuse or dependence, and meeting
      DSM-IV criteria for abuse or dependence. RESULTS: Significant lifetime use of
      illicit substances (defined as use 10 or more times) was reported by only 6.4% of
      the sample. Meaningful analyses were possible for use of any substance and each
      of the five substances individually, but for symptoms or a diagnosis of
      abuse/dependence meaningful analyses were possible only for any substance and
      cannabis. Full twin models uniformly found twin resemblance to be due largely or
      entirely to genetic factors. Best-fit models for all analyses included only
      genetic and individual-specific environmental effects with heritability estimates
      ranging from 58% to 81%. CONCLUSION: In accord with prior results from the USA
      and Australia, genetic factors appear to play an important role in the etiology
      of use and abuse/dependence of illicit drugs in Norway.

PMID- 16650347
TI  - The role of alcohol in suicide: a case-control psychological autopsy study.
AB  - BACKGROUND: The purpose of the study was to estimate the proportion of alcohol
      abuse and dependence (AAD) among suicides and controls, and to compare the
      incidence of AAD documented by clinicians with diagnoses derived from a research
      protocol. METHOD: AAD according to DSM-IV was diagnosed on the basis of
      interviews with relatives of people who committed suicide and with controls. A
      total of 427 people who committed suicide during one year were paired by region,
      gender, age and nationality with controls randomly selected from general
      practitioners' lists. RESULTS: Alcohol abuse was found in 10% and alcohol
      dependence in 51% of suicide cases. The corresponding figures for controls were
      7% and 14% respectively. AAD was a statistically significant predictor of
      completed suicides, while abstinence was a significant predictor for female
      suicides and former use a significant predictor for older male suicides. AAD was
      diagnosed in 68% of male and 29% of female suicides. Middle-aged (35-59 years)
      males who committed suicide had the highest risk of alcohol dependence. Among
      suicide cases only 29% had received a lifetime diagnosis of AAD, against 23% of
      controls. CONCLUSIONS: AAD was significantly more prevalent among suicides than
      controls. Overall, the proportion of male suicides affected by alcohol was the
      same in the present psychological autopsy study as in our previous findings for
      Estonia on the aggregate level, while the share of female suicides with an AAD
      diagnosis was dramatically higher on the individual level. AAD is markedly
      underdiagnosed by general practitioners and clinicians.

PMID- 16650348
TI  - Assessing personality traits associated with depression: the utility of a tiered
      model.
AB  - BACKGROUND: We sought to develop a refined measure of eight personality traits or
      constructs observed in those who develop depression. We report the psychometric
      properties of the derived Temperament and Personality (T and P) questionnaire, as
      well as a pilot study examining its capacity to differentiate over-represented
      personality traits in those with depression. METHOD: The factor structure of the
      T&P measure was examined in a general practice sample of 529 subjects. We imposed
      a range of factorial solutions to determine how higher-order molar constructs
      arborized to eight lower-order constructs. Scale scores generated at each derived
      tier were contrasted for 52 out-patients with major depression and control
      subjects from the general practice sample to pursue over-represented personality
      constructs, and to clarify if an optimal number of constructs could be
      identified. RESULTS: In the factor analysis, some 90% of the items loaded on
      their a priori construct. The questionnaire showed high internal consistency,
      test-retest reliability and minimal sensitivity to mood state effects. Analyses
      rejected the hypothesis that risk to depression might be generally affected by
      individuals merely scoring high on all 'normal' personality styles, whether
      higher-order or lower-order traits. CONCLUSIONS: Findings suggest that, while
      identified constructs linked well with the widely accepted theoretical model of
      personality (the Five Factor Model) at one tier, such a fixed model may be too
      inflexible. We therefore detail potential advantages to using a multi-tiered
      model of personality traits in application studies.

PMID- 16650349
TI  - Abnormal function of the brain system supporting motivated attention in medicated
      patients with schizophrenia: an fMRI study.
AB  - BACKGROUND: Patients with schizophrenia have an impaired ability to generate
      activity that is appropriate to current circumstances and goals. METHOD: We
      report a study using functional magnetic resonance imaging (fMRI) to examine
      cerebral activity during a three-tone auditory oddball target detection task in a
      sample of 28 patients with schizophrenia and 28 healthy controls. RESULTS: The
      patients exhibited significantly less activation in response to target stimuli
      relative to baseline in an extensive set of sites in association neocortex,
      paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a
      normal level of activation in the sensorimotor cortex. Comparison of activity
      elicited by rare target stimuli with that elicited by equally rare novel stimuli
      makes it possible to distinguish cerebral activity associated with attention to
      behaviourally salient stimuli from activity associated with attending to other
      attention-capturing stimuli. This comparison revealed that the patients with
      schizophrenia also exhibited a deficit in activation of basal forebrain areas
      that mediate motivation during the processing of behaviourally salient stimuli,
      including the amygdala, ventral striatum, orbital frontal cortex and rostral
      anterior cingulate cortex. CONCLUSION: Patients with schizophrenia have a deficit
      in function of the brain system concerned with mediating motivation, in addition
      to a more general deficit in the cerebral response to attention-captivating
      stimuli.

PMID- 16650350
TI  - Menopause and osteoporosis.

PMID- 16650351
TI  - Peritoneal tuberculosis.

PMID- 16650352
TI  - Re: a randomized trial comparing oral misoprostol with intra-amniotic
      prostaglandin F2alpha for second trimester terminations.

PMID- 16650354
TI  - Re: choice of surgery for stress incontinence.

PMID- 16650356
TI  - Multiple repeat caesarean sections: complications and outcomes.
AB  - OBJECTIVE: To compare the complications and outcomes of Caesarean section (CS) in
      women who have had three or more previous lower segment Caesarean sections with
      those in women with one previous CS. METHODS: We performed a retrospective study
      of 371 patients undergoing repeat CS. Of these, 115 (31%) had previously had
      three or more Caesarean sections (group 1) and 256 (69%) had previously had one
      CS (group 2). All 371 patients had the repeat CS performed at Abha Maternity
      Hospital, Saudi Arabia between June 2002 and May 2004. Demographic data,
      complications, and outcomes were compared using the Student t and chi-square
      tests. RESULTS: There were statistically significant differences between the two
      groups with respect to mean maternal age, parity, gestation at delivery, and
      experience of the surgeon (P < 0.05). CS was performed as an emergency in 38
      (32.9%) and 186 (72.6%) of patients in groups 1 and 2 respectively (P < 0.05).
      The consultant was involved in the decision to perform CS in 215 (84.6%) of
      patients with one previous CS. There were significant differences between the two
      groups in the type of skin incision, the presence of dense adhesions during
      surgery, and bladder injury (P < 0.05). There were no statistically significant
      differences in birth weight, stillbirth rate, low Apgar score, blood loss during
      surgery, duration of surgery, or the duration of postoperative hospital stay.
      CONCLUSION: The prevalence of dense intra-abdominal adhesions and of bladder
      injury during CS was higher in women with a history of three or more previous CS
      than in women with one previous CS. Placenta previa and Caesarean hysterectomy
      occurred with equal frequency in each group, and wound dehiscence and uterine
      rupture were rare.

PMID- 16650357
TI  - Intra-amniotic sludge, short cervix, and risk of preterm delivery.
AB  - OBJECTIVE: To evaluate the association between intra-amniotic sludge seen at
      cervical ultrasound and preterm delivery. METHOD: This retrospective study
      included women at high risk for preterm delivery who were referred for second
      trimester cervical length measurement by ultrasound between 18 and 32 weeks'
      gestation. Patients with multiple gestations, cerclage, or preterm labour were
      excluded. Ultrasound images were reviewed by two independent observers and
      divided into three groups: (1) no amniotic sludge, (2) light sludge, and (3)
      dense sludge in the amniotic fluid. The primary outcome measures were delivery
      within 14 days of examination and delivery before 34 weeks' gestation. Logistic
      regression analyses were performed to adjust for confounding factors. RESULTS:
      Eighty-nine patients met the inclusion criteria. Mean gestational age at
      presentation was 25.8 +/- 4.4 weeks, and mean cervical length was 33 +/- 12 mm.
      The prevalence of light and dense amniotic fluid sludge was 10.1% and 5.6%,
      respectively. Delivery within 14 days of examination occurred in four (5.3%)
      women with no sludge, in two (22.2%) women with light sludge, and in three
      (60.0%) women with dense sludge (P < 0.01). Delivery before 34 weeks occurred in
      five (6.7%), four (44.4%) and four (80.0%) women, respectively (P < 0.01).
      Logistic regression analyses demonstrated that light amniotic fluid sludge, dense
      sludge, and cervical length of less than 25 mm were all significant and
      independent predictors of delivery within 14 days of examination and delivery
      prior to 34 weeks. CONCLUSION: The presence of amniotic fluid sludge is
      associated with delivery within 14 days and delivery before 34 weeks' gestation.

PMID- 16650358
TI  - Perspectives on the management of the short cervix identified by transvaginal
      ultrasound during pregnancy: an update for Canadian obstetrical caregivers.
AB  - A shortened cervix is often considered to be equivalent to cervical
      insufficiency, and a cerclage may be offered as an intervention to prolong
      pregnancy; however, we may not be differentiating between true cervical
      insufficiency and intrauterine causes of cervical shortening. A recent meta
      analysis found no significant reduction in preterm birth < 35 weeks' gestation in
      women with cerclage compared with no cerclage in the total population of women
      studied. However, there was a potentially significant reduction in preterm birth
      < 35 weeks among women with a singleton pregnancy (relative risk [RR] 0.74; 95%
      confidence intervals [CI] 0.57-0.96), with a singleton pregnancy and a previous
      preterm birth (RR 0.61; 95% CI 0.40-0.92), and with a singleton pregnancy with a
      previous mid-trimester loss (RR 0.57; 95% CI 0.33-0.99). An increase was found in
      preterm birth among twin gestations with cerclage placed for a shortened cervix
      on transvaginal ultrasound (RR 2.15; 95% CI 1.15-4.01). This unexpected finding
      underscores the possibility of harm with this intervention. This intervention
      deserves further study. A national registry or database would allow us to
      identify women who may benefit more significantly from cerclage by collecting
      data on possible confounding effects such as concomitant intrauterine infection
      or placental disease.

PMID- 16650359
TI  - The evaluation of the fetal fibronectin test for prediction of preterm delivery
      in symptomatic patients.
AB  - OBJECTIVE: This study was conducted to evaluate the usefulness of testing for
      fetal fibronectin (fFN) to rule out the diagnosis of preterm labour in
      symptomatic patients in a Canadian setting. METHODS: This was a prospective,
      blinded clinical evaluation of fFN testing in women presenting with threatened
      preterm labour at between 24 and 34 weeks' gestation at two Canadian tertiary
      care centres. RESULTS: Of the 149 women tested, 32 had a positive fFN test. In
      the total patient population, 10.1% delivered within seven days of testing, and
      18.2% delivered prior to 34 weeks. A negative fFN result was associated with a
      97.4% likelihood of delivering more than seven days after testing and with a
      91.4% chance of delivering after 34 weeks. CONCLUSION: The fFN test appears to
      provide useful information in the risk assessment of Canadian women presenting
      with symptoms compatible with preterm labour. A negative test has a high
      predictive value for delivering more than seven days after presentation.

PMID- 16650360
TI  - Safety of a new transobturator suburethral synthetic sling (TVT-O) procedure
      during the training phase.
AB  - OBJECTIVE: The TVT-O (Ethicon, Somerville, NJ) is a new transobturator
      suburethral synthetic sling used in the treatment of female stress urinary
      incontinence (SUI). This study aimed to evaluate the complication rates and
      procedural times associated with performing this procedure during a period of
      transition from the retropubic tension-free vaginal tape (TVT) procedure to the
      transobturator TVT-O procedure. METHODS: We performed a retrospective analysis of
      the first 50 patients to undergo the TVT-O procedure in one gynaecologist's
      practice. All patients had SUI or mixed urinary incontinence. Operative times and
      intraoperative and perioperative complications were recorded. At the two-week and
      six- to eight-week postoperative reviews, a urogenital history and examination
      were performed. RESULTS: The only complications encountered were two cases (4%)
      of urinary tract infection and one case (2%) of superficial wound infection.
      There were no cases of postoperative voiding difficulty, hemorrhage, hematoma,
      persistent groin pain, or vascular or visceral injuries. The mean procedural time
      was 21 minutes. CONCLUSION: These preliminary results indicate that the TVT-O
      procedure is a safe treatment for female SUI even during the training phase. In
      light of the safety and the ease of transition to this technique, this finding is
      encouraging for surgeons who are making the transition from other surgical
      procedures for female SUI to the transobturator TVT-O.

PMID- 16650361
TI  - Pregnancy outcomes after assisted reproductive technology.
AB  - OBJECTIVE: To review the effect of assisted reproductive technology (ART) on
      perinatal outcomes, to provide guidelines to optimize obstetrical management and
      counselling of Canadian women using ART, and to identify areas specific to birth
      outcomes and ART requiring further research. OPTIONS: Perinatal outcomes of ART
      pregnancies in subfertile women are compared with those of spontaneously
      conceived pregnancies. Perinatal outcomes are compared between different types of
      ART. OUTCOMES: This guideline discusses the adverse outcomes that have been
      recorded in association with ART, including obstetrical complications, adverse
      perinatal outcomes, multiple gestations, structural congenital abnormalities,
      chromosomal abnormalities, imprinting disorders, and childhood cancer. EVIDENCE:
      The Cochrane Library and MEDLINE were searched for English-language articles from
      1990 to February 2005, relating to assisted reproduction and perinatal outcomes.
      Search terms included assisted reproduction, assisted reproductive technology,
      ovulation induction, intracytoplasmic sperm injection (ICSI), embryo transfer,
      and in vitro fertilization (IVF). Additional publications were identified from
      the bibliographies of these articles as well as the Science Citation Index.
      Studies assessing gamete intrafallopian transfer (GIFT) and zygote intrafallopian
      transfer (ZIFT) were excluded since they are rarely used in Canada. All study
      types were reviewed. Randomized controlled trials were considered evidence of the
      highest quality, followed by cohort studies. Key studies and supporting data for
      each recommendation are summarized with evaluative comments and referenced.
      VALUES: The evidence collected was reviewed by the Genetics Committee and the
      Reproductive Endocrinology Infertility Committee of the Society of Obstetricians
      and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of
      Evidence Guidelines developed by the Canadian Task Force on the Periodic Health
      Examination. BENEFITS, HARMS, AND COSTS: The type and magnitude of benefits,
      harms, and costs expected for patients from guideline implementation. This
      guideline has been reviewed by the Genetics Committee and the Reproductive
      Endocrinology and Infertility Committee, and approved by the Executive and
      Council of the Society of Obstetricians and Gynaecologists of Canada and the
      Board of the Canadian Fertility and Andrology Society. RECOMMENDATIONS: 1.
      Spontaneous pregnancies in untreated infertile women may be at higher risk for
      obstetrical complications and perinatal mortality than spontaneous pregnancies in
      fertile women. Further research is required to clarify the contribution of
      infertility itself to adverse obstetrical and perinatal outcomes. (II-2A) 2. All
      men with severe oligozoospermia or azoospermia should be offered genetic/clinical
      counselling for informed consent and offered karyotyping for chromosomal
      abnormalities before attempting IVF-ICSI. They should be made aware of the
      availability of tests for Y chromosome microdeletion. Some patients may consider
      the option of donor insemination. (II-3B) 3. Couples exploring IVF-ICSI when the
      man has obstructive azoospermia should be offered genetic/clinical counselling
      for informed consent and offered genetic testing for alterations in genes
      associated with cystic fibrosis (CF) before attempting IVF-ICSI. (II-2A) 4.
      Pregnancies achieved by ovarian stimulation with gonadotropins and intrauterine
      insemination are at higher risk for perinatal complications, and close
      surveillance during pregnancy should be considered. It remains unclear if these
      increased risks are attributable to the underlying infertility, characteristics
      of the infertile couple, or use of assisted reproductive techniques. Multiple
      gestations remain a significant risk of gonadotropin treatment. (II-2A) 5.
      Pregnancies achieved by IVF with or without ICSI are at higher risk for
      obstetrical and perinatal complications than spontaneous pregnancies, and close
      surveillance during pregnancy should be considered. It remains unclear if these
      increased risks are attributable to the underlying infertility, characteristics
      of the infertile couple, or use of assisted reproductive techniques. (II-2A) 6.
      Women undergoing ART should be informed about the increased rate of obstetrical
      interventions such as induced labour and elective Caesarean delivery. (II-2A) 7.
      Couples suffering from infertility who are exploring treatment options should be
      made aware of the psychosocial implications of ART. Further research into the
      psychosocial impact of ART is needed. (II-2A) 8. Singleton pregnancies achieved
      by assisted reproduction are at higher risk than spontaneous pregnancies for
      adverse perinatal outcomes, including perinatal mortality, preterm delivery, and
      low birth weight, and close surveillance during pregnancy should be available as
      needed. (II-2A) 9. A significant risk of ART is multiple pregnancies. Infertile
      couples need to be informed of the increased risks of multifetal pregnancies.
      Although dichorionic twins are most common, the incidence of monochorionic twins
      is also increased. Risks of multiple pregnancies include higher rates of
      perinatal mortality, preterm birth, low birth weight, gestational hypertension,
      placental abruption, and placenta previa. Perinatal mortality in assisted
      conception twin pregnancies appears to be lower than in spontaneously conceived
      twin pregnancies. (II-2A) 10. When multifetal reduction is being considered for
      high-order multiple pregnancies, psychosocial counselling should be readily
      available. Careful surveillance for fetal growth problems should be undertaken
      after multifetal reduction. (II-2A) 11. To reduce the risks of multiple
      pregnancies associated with ART and to optimize pregnancy rates, national
      guidelines should be developed on the number of embryos replaced according to
      characteristics such as patient's age and grade of embryos. (II-2A) 12. Further
      epidemiologic and basic science research is needed to help determine the etiology
      and extent of the increased risks to childhood and long-term growth and
      development associated with ART. (II-2A) 13. Discussion of options for prenatal
      screening for congenital structural abnormalities in pregnancies achieved by ART
      is recommended, including appropriate use of biochemical and sonographic
      screening. (II-2A) 14. Further epidemiologic and basic science research is needed
      to help determine the etiology and extent of the increased risks of congenital
      abnormalities associated with ART. (II-2A) 15. Couples considering IVF-ICSI for
      male-factor infertility should receive information, and if necessary formal
      genetic counselling, about the increased risk of de novo chromosomal
      abnormalities (mainly sex chromosomal anomalies) associated with their condition.
      Prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis should be
      offered to these couples if they conceive. (II-2A) 16. Further epidemiologic and
      basic science research is needed to help determine the etiology and extent of the
      increased risks of chromosomal abnormalities associated with ART. (II-2A) 17.
      Discussion of options for prenatal screening and testing for aneuploidy in
      pregnancies achieved by ART, adapted for maternal age and number of fetuses, is
      recommended, including appropriate use of biochemical and sonographic screening.
      (II-2A) 18. The precise risks of imprinting and childhood cancer from ART remain
      unclear but cannot be ignored. Further clinical research, including long-term
      follow-up, is urgently required to evaluate the prevalence of imprinting
      disorders and cancers associated with ART. (II-2A) 19. The clinical application
      of preimplantation genetic diagnosis must balance the benefits of avoiding
      disease transmission with the medical risks and financial burden of in vitro
      fertilization. Further ethical discussion and clinical research is required to
      evaluate appropriate indications for preimplantation genetic diagnosis. (III-B).

PMID- 16650362
TI  - [Serum urate levels and urinary uric acid excretion in subjects with metabolic
      syndrome].
AB  - BACKGROUND AND OBJECTIVES: Hyperuricemia is considered a feature of the metabolic
      syndrome (MS) despite serum uric acid (SUA) is not considered a diagnostic
      criterion. The main physiopathological disturbance leading to the increased SUA
      is not completely understood. PATIENTS AND METHOD: Descriptive study without drug
      intervention including 141 subjects (NCEP-ATPIII: 105 with MS and 36 without MS).
      Serum UA levels were compared in subjects with and without MS. The mechanism of
      the rise in SUA levels was assessed (overproduction or decreased renal
      excretion). The relation of SUA levels to the HOMA index was also evaluated.
      RESULTS: Subjects with MS showed significantly higher SUA levels (5.6 [1.6] vs
      4.6 [1.7] mg/dl, p = 0.002), and lower urinary UA excretion than subjects without
      MS (UA clearance 3.60 [2.41] vs 4.65 [3.04] ml/min/m2, p = 0.049; excreted
      fraction of filtered UA 7.15 [4.72] vs 9.81 [6.78%], p = 0.045). Sex (male 6.1
      [1.6] vs female 4.9 [1.6] mg/dl, p < 0.001), alcohol intake (drinkers 6.1 [1.8]
      vs non-drinkers 5.2 [1.6] mg/dl, p < 0.01), and MS (present 5.6 [1.6] absent 4.6
      [1.7] mg/dl, p < 0.002), were significantly associated with SUA. In the multiple
      regression analysis, sex and MS were independently associated with SUA.
      CONCLUSIONS: This study demonstrates significantly higher SUA levels in subjects
      with MS. A decreased urinary UA excretion, instead of urate overproduction, was
      the leading mechanism to explain high SUA. Serum UA levels were not associated
      with the HOMA index.

PMID- 16650363
TI  - [Effect of statin treatment begun early after acute myocardial infarction on
      endothelial function in patients with normal levels of cholesterol. VAATOPE Study
      (VAlue of ATOrvastatin in Postinfarction Endothelium)].
AB  - BACKGROUND AND OBJECTIVE: Recent studies have suggested that statins reduce the
      rate of subsequent coronary events when these drugs are indicated early alter an
      acute coronary event. One potential mechanism by which these drugs might reduce
      the likelihood of such events is by enhancing endothelial function. The aim of
      this study was to determine whether early cholesterol reduction with atorvastatin
      improved endothelial function after acute myocardial infarction in patients with
      normal cholesterol levels. PATIENTS AND METHOD: Patients with a first acute
      myocardial infarction and normal levels of cholesterol were assigned to treatment
      with 10 mg atorvastatin (n = 15) or placebo (n = 15) for 8 weeks. Patients who
      had previously received treatment with statins were excluded. Brachial ultrasound
      was used to measure endothelium-dependent flow-mediated dilation and response to
      endothelium-independent nitroglycerin. Total and LDL cholesterol levels and the
      distribution of risk factors were similar on admission and before randomization
      in both groups. All patients were assessed between 5 and 7 days postinfarction
      and after 8 weeks. RESULTS: Total and LDL cholesterol levels were significantly
      decreased after atorvastatin treatment. Total cholesterol decreased by 11% (p <
      0.01) and LDL cholesterol by 18% (p < 0.01). Without atorvastatin flow-mediated
      dilation was unchanged (mean [SEM] 9.3 [1.7%] to 10.6 [1.7%]) but it increased
      with atorvastatin (8.9 [1.4%] to 16.5 [1.7%], p < 0.05). The response to
      nitroglycerin was similar in both groups during the period of study. CONCLUSIONS:
      The early administration of atorvastatin appears to enhance endothelial function
      in patients with acute myocardial infarction and normal levels of cholesterol.

PMID- 16650364
TI  - [The usefulness of hospital at home in nephrology].
AB  - BACKGROUND AND OBJECTIVE: The Hospital at Home Unit (HHU) is a medical care model
      effective in different fields of medical and surgical conditions. The objective
      of the study was to analyse the utility of moving acute nephrologic patients to a
      HHCU. PATIENTS AND METHOD: We review the Nephrology Service requests to move
      patients to the HHU the last 3 years. The results were compared with those
      obtained from the rest of patients admitted at the HHU during the same period.
      RESULTS: The requests number was 85 and 79 (93%) patients were included for the
      study. Patients had high comorbidity (Charlson index mean, 3.75) and acute
      medical problems. The length of stay at the HHU was 12.65 days. The total
      intervention rate was 1.23 interventions/day. In 71 cases (89.9%) the hospital
      discharge was at the patient's home. In 8 cases the readmission at the hospital
      was required to solve the medical process. Hospital readmissions after the HHCU
      discharge before 30 days was 6.3%. No statistical differences were found between
      nephrology patients and the rest of HHU patients when comparing the intervention
      rates, the percentage of home discharges and the hospital readmissions.
      CONCLUSIONS: The moving of nephrologic acute patients to a HHU is a save choice
      and well accepted by patients and their families.

PMID- 16650365
TI  - [Twenty five years of hospital at home in Spain].

PMID- 16650366
TI  - [Early effect of statins after myocardial infarction. A statin-induced
      pleiotropic effect?].

PMID- 16650367
TI  - [Newborn screening of hemoglobinopathies: considerations on its application in
      Spain].

PMID- 16650368
TI  - [HIV entry into the cells--mechanisms and therapeutic possibilities].
AB  - Human immunodeficiency virus (HIV) entry into cells is the first step in the
      viral replication cycle, which has been explored as a new therapeutic target. A
      better knowledge of the mechanisms involved in the entry process has led to the
      development of agents, which may inhibit each of the different steps of the viral
      entry process: attachment of the gp120 to the CD4 cell receptor; binding of the
      gp120 to CCR5 or CXCR4 coreceptors; and the fusion of viral and cell membranes.
      Entry inhibitors are the latest family of antiretroviral compounds, being
      enfuvirtide, a fusion inhibitor, the first approved. Several other entry
      inhibitors are currently in clinical development and hopefully soon will be part
      of the therapeutic armamentarium against HIV.

PMID- 16650369
TI  - [Pancreatic cyst in a 60-year-old woman].

PMID- 16650370
TI  - [Adequate use of drugs and therapeutic efficacy].

PMID- 16650371
TI  - [Bacteremia caused by Hafnia alvei in an intensive care neonatal unit].

PMID- 16650372
TI  - [Low diagnostic sensitivity of clinical models for prediction of pulmonary
      embolism].

PMID- 16650373
TI  - [Reduction of pressure effect in patients with morbid obesity submitted to
      bariatric surgery].

PMID- 16650374
TI  - [Ventilation perfusion scintigraphy and CT: comparative study in the diagnosis of
      pulmonary thromboembolism].

PMID- 16650375
TI  - [Chronic urticaria and angioedema in Giardia lamblia infection].

PMID- 16650376
TI  - [Incrusted cystitis due to Pseudomonas aeruginosa: an unusual cause of mictional
      syndrome].

PMID- 16650377
TI  - [Acquired inhibitor of factor V: an uncommon cause of prolonged coagulation
      tests].

PMID- 16650378
TI  - Investigation of the interaction of pig muscle lactate dehydrogenase with acidic
      phospholipids at low pH.
AB  - Interaction of pig muscle lactate dehydrogenase (LDH) with acidic phospholipids
      is strongly dependent on pH and is most efficient at pH values<6.5. The
      interaction is ionic strength sensitive and is not observed when bilayer
      structures are disrupted by detergents. Bilayers made of phosphatidylcholine (PC)
      do not bind the enzyme. The LDH interaction with mixed composition bilayers
      phosphatidylserine/phosphatidylcholine (PS/PC) and
      cardiolipin/phosphatidylcholine (CL/PC) leads to dramatic changes in the specific
      activity of the enzyme above a threshold of acidic phospholipid concentration
      likely when a necessary surface charge density is achieved. The threshold is
      dependent on the kind of phospholipid. Cardiolipin (CL) is much more effective
      compared to phosphatidylserine, which is explained as an effect of availability
      of both phosphate groups in a CL molecule for interaction with the enzyme. A
      requirement of more than one binding point on the enzyme molecule for the
      modification of the specific activity is postulated and discussed. Changes in CD
      spectra induced by the presence of CL and PS vesicles evidence modification of
      the conformational state of the protein molecules. In vivo qualitative as well as
      quantitative phospholipid composition of membrane binding sites for LDH molecules
      would be crucial for the yield of the binding and its consequences for the enzyme
      activity in the conditions of lowered pH.

PMID- 16650379
TI  - Mechanical compressive loading stimulates the activity of proximal region of
      human COL2A1 gene promoter in transfected chondrocytes.
AB  - Previous studies have demonstrated that the mechanical compressive loading
      affects the biosynthesis of chondrocytes seeded in three dimensional scaffolds.
      In this study, the level of type II collagen mRNA expression was increased by a
      continuous dynamic compression at 10% compressive strain and 0.1 Hz in
      chondrocytes seeded in a biodegradable, elastomeric scaffold, poly(L-lactide-co
      epsilon-caprolactone) (PLCL). To further examine this molecular mechanism, the
      promoter region of COL2A1 gene, which is encoding type II collagen, was analyzed
      using rabbit chondrocytes transfected with luciferase reporter vectors containing
      the 5'-flanking regions of human COL2A1 gene. A deletion mutant analysis revealed
      that the most active short promoter in response to continuous dynamic compression
      is in the region between -509 and -109 base pairs, where the transcription factor
      Sp1 is located. Additionally, an mRNA decay experiment using transcription
      inhibitor actinomycin D demonstrated that dynamic compression do not stabilize
      type II collagen mRNA. Our results indicate that mechanical compression increases
      the level of type II mRNA expression by transcriptional activation possibly
      through the Sp1 binding sites residing in the proximal region of the COL2A1 gene
      promoter.

PMID- 16650380
TI  - Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4).
AB  - The production of IL-8 can be induced by LPS via TLR4 signaling pathway. In this
      study, we tested the effect of a herbal melanin (HM) extract, from black cumin
      seeds (Nigella sativa L.), on IL-8 production. We used HM and LPS in parallel to
      induce IL-8 production by THP-I, PBMCs, and TLR4-transfected HEK293 cells. Both
      HM and LPS induced IL-8 mRNA expression and protein production in THP-1 and
      PBMCs. On applying similar treatment to HEK293 cells that express TLR4, MD2, and
      CD14, both HM and LPS significantly induced IL-8 protein production. We have also
      demonstrated that HM and LPS had identical effects in terms of IL-8 stimulation
      by HEK293 transfected with either TLR4 or MD2-CD14. Melanin extracted from N.
      sativa L. mimics the action of LPS in the induction of IL-8 by PBMC and the other
      used cell lines. Our results suggest that HM may share a signaling pathway with
      LPS that involves TLR4.

PMID- 16650381
TI  - The Arf-family protein, Arl8b, is involved in the spatial distribution of
      lysosomes.
AB  - Lysosomes are late-endocytic organelles which primarily contribute to degradation
      and recycling of cellular material. From a previous proteomics study of purified
      rat liver lysosomal membranes we identified a protein from the Arf-family of
      small GTPases, Arl8b. Although proteins of the Arf-family have roles in a wide
      range of cellular functions, most notably roles in protein/vesicular trafficking,
      Arl8b represents the first from this protein family to be associated with a late
      endocytic organelle. We demonstrate the co-localization of this protein with
      various lysosomal markers in different cell lines by confocal-immunofluorescence
      microscopy. We also show that GTP-restricted mutant Arl8b localizes to lysosomes
      and causes their redistribution to the periphery of the cell and into membrane
      projections. This indicates that Arl8b is involved in trafficking processes for
      lysosomes.

PMID- 16650382
TI  - Beneficial effects of candesartan, an angiotensin II type 1 receptor blocker, on
      beta-cell function and morphology in db/db mice.
AB  - Several epidemiological studies suggested that treatment with angiotensin II type
      1 receptor blocker (ARB) provided a risk reduction of developing type 2 diabetes.
      In this study, we investigated whether and how ARB treatment can improve
      abnormalities of pancreatic islets in diabetes state. We randomized db/db mice, a
      model of type 2 diabetes with obesity, at the age of 8 weeks to receive
      candesartan, an ARB, for 6 weeks. We also studied age-matched db/misty mice as
      control. Glucose tolerance test revealed that candesartan treatment improved
      glucose tolerance with the modest increase in serum insulin level in db/db mice.
      Concurrently, candesartan increased beta-cell mass, increased staining intensity
      of insulin, and decreased staining intensity of components of NAD(P)H oxidase,
      p22phox and gp91phox, and those of oxidative stress markers in beta-cells. These
      changes were accompanied by reduction of mitochondrial volume. Treatment with
      candesartan also reduced fibrosis in and around the islets and prevented the loss
      of endothelial cells in islets. Our results showed that candesartan partially
      prevented deterioration of glucose tolerance by providing protection against
      progressive beta-cell damage in diabetes.

PMID- 16650383
TI  - TGF-beta signaling pathway inactivation and cell cycle deregulation in the
      development of gastric cancer: role of the beta-spectrin, ELF.
AB  - We have shown that loss of ELF, a stem cell adaptor protein, disrupts TGF-beta
      signaling through Smad3 and Smad4 localization. Notably elf(+/-)/smad4(+/-) mice
      develop gastric cancer presenting this as an important model for analyzing
      molecular event in gastric carcinogenesis. To gain further insight into the
      functional role of ELF in gastric cancer suppression, we carried out a detailed
      characterization of cell cycle events leading to gastric tumorigenesis. elf(-/-)
      cells and elf(+/-)/smad4(+/-) mice demonstrate a marked alteration of cell cycle
      regulators, such as Cdk4, K-Ras, and p21. Levels of Cdk4 increased compared to
      normal controls, suggesting loss of ELF results in functional abnormalities in
      cell cycle regulation. We further demonstrate that the elf(-/-) MEFs show a
      disruption of G1/S cell cycle transition and a significant reduction in
      senescence. Thus, in response to ELF deficiency, the abnormalities of G1/S
      checkpoint and senescence contribute their increment of susceptibility to
      malignant transformation.

PMID- 16650384
TI  - A further study of a possible locus for schizophrenia on the X chromosome.
AB  - Several studies suggest that the X chromosome may contain a gene for
      schizophrenia. In the present study, we recruited 142 male schizophrenic patients
      and their biological mothers from all parts of the United Kingdom to detect a
      genetic association for the SYP/CACNA1F locus in the Xp11 region and the FACL4
      locus in the Xq22.3-Xq23 region. The haplotype-based haplotype relative risk
      (HHRR) analysis showed allelic association for rs2071316 (chi2=6.85, P=0.009) and
      rs5905724 (chi2=5.3, P=0.021) at the CACNA1F locus, but not for rs5943414 and
      rs1324805 at the FACL4 locus and rs3817678 at the SYP locus. The haplotype
      analysis showed a weak association for the rs3817678-rs2071316-rs5905724
      haplotypes (chi2=12.19, df=4, P=0.016) but did not show such an association for
      the rs5943414-rs1324805 haplotypes (chi2=3.96, df=2, P=0.138). Because the
      linkage disequilibrium signal was detected only at the CACNA1F locus, this gene
      should perhaps be considered as being a candidate for schizophrenia although
      further work is needed to draw firm conclusions.

PMID- 16650385
TI  - Superoxide radical production by allopurinol and xanthine oxidase.
AB  - Oxypurinol, an inhibitor of xanthine oxidase (XO), is being studied to block XO
      catalyzed superoxide radical formation and thereby treat and protect failing
      heart tissue. Allopurinol, a prodrug that is converted to oxypurinol by xanthine
      oxidase, is also being studied for similar purposes. Because allopurinol, itself,
      may be generating superoxide radicals, we currently studied the reaction of
      allopurinol with xanthine oxidase and confirmed that allopurinol does produce
      superoxide radicals during its conversion to oxypurinol. At pH 6.8 and 25 degrees
      C in the presence of 0.02 U/ml of XO, 10 and 20 microM allopurinol both produced
      10 microM oxypurinol and 2.8 microM superoxide radical (determined by cytochrome
      C reduction). The 10 microM allopurinol was completely converted to oxypurinol,
      while the 20 microM allopurinol required a second addition of xanthine oxidase to
      complete the conversion. Fourteen percent of the reducing equivalents donated
      from allopurinol or xanthine reacted with oxygen to form superoxide radicals.
      Superoxide dismutase prevented the reduction of cytochrome C by these substrates.
      At higher xanthine oxidase concentrations, or at lower temperatures, more of the
      20 microM allopurinol was converted to oxypurinol during the initial reaction. At
      lower xanthine oxidase concentrations, or higher temperatures, less conversion
      occurred. At pH 7.8, the amount of superoxide radicals produced from allopurinol
      and xanthine was nearly doubled. These results indicate that allopurinol is a
      conventional substrate that generates superoxide radicals during its oxidation by
      xanthine oxidase. Oxypurinol did not produce superoxide radicals.

PMID- 16650386
TI  - Serum free Fatty acids and glucose metabolism, insulin resistance in
      schizophrenia with chronic antipsychotics.
AB  - BACKGROUND: Weight gain and type 2 diabetes mellitus (DM) are often linked to
      antipsychotics treatment. The aim of the study is to investigate serum free fatty
      acids (FFA) levels in schizophrenic patients who received long-term
      antipsychotics treatment, and to explore the associations between serum FFA and
      fasting blood glucose, and insulin resistance. METHODS: 308 inpatients with
      schizophrenia who met with the criteria of DSM-IV were recruited into this study,
      and were divided into four groups: control subjects, single obesity, impaired
      glucose tolerance (IGT) and type 2 DM according to different body mass index,
      fasting blood glucose level and 2-hour postprandial blood glucose. Serum FFA was
      measured with colorimetry. Serum insulin and leptin were measured with
      radioimmunoassay respectively. RESULTS: There was a significant elevation in
      serum FFA levels in schizophrenic patients who received long-term antipsychotics
      treatment, especially in single obesity, IGT, and DM groups. The elevated serum
      FFA was remarkably positive correlated with fasting blood glucose and insulin
      resistance. CONCLUSIONS: The study suggested the elevated serum FFA in
      schizophrenic patients with long-term antipsychotics treatment affected the blood
      glucose metabolism, may have played an important role in insulin resistance and
      type 2 DM, and was also an important trait of metabolic syndromes.

PMID- 16650387
TI  - Electro-acupuncture attenuates stress-induced defecation in rats with chronic
      visceral hypersensitivity via serotonergic pathway.
AB  - Acupuncture has long been used for patients with irritable bowel syndrome.
      However, it has remained unclear. The aim of this study was to testify the effect
      of electro-acupuncture(EA) on (1) visceral hypersensitivity induced by the
      mechanical colorectal irritation during postnatal development of rats, and (2)
      stress-induced colonic motility changes on rats with chronic visceral
      hypersensitivity. The abdominal withdrawal reflex (pain threshold and score) for
      visceral hypersensitivity and fecal pellet output for motor dysfunction were
      selected as two indexes for measurement. In addition, the effect of EA on 5
      HT(4a) receptor and serotonin transporter (SERT) expression in the colon mucosa
      was analyzed semi-quantitatively through immunohistochemistry and 5-HT
      concentration in the colon tissue was observed through spectro-photo-fluorimeter
      detection, respectively. Our results showed that EA significantly elevated pain
      threshold, decreased the scores and also decreased fecal pellet output during
      water avoid stress. Furthermore, EA decreased 5-HT concentration in colon in rats
      with CVH and CVH rats with water avoidance stress, and increased the 5-HT(4a) and
      SERT expression in rats with CVH. Thus, it can be concluded that EA attenuates
      behavioral hyperalgesia and stress-induced colonic motor dysfunction in CVH rats
      via serotonergic pathway.

PMID- 16650388
TI  - Cardiovascular responses and neurotransmitter changes during static muscle
      contraction following blockade of inducible nitric oxide synthase (iNOS) within
      the ventrolateral medulla.
AB  - The enzyme nitric oxide synthase (NOS) which is necessary for the production of
      nitric oxide from L-arginine exists in three isoforms: neuronal NOS (nNOS),
      endothelial NOS (eNOS), and inducible NOS (iNOS). Our previous studies have
      demonstrated the roles of nNOS and eNOS within the rostral (RVLM) and caudal
      ventrolateral medulla (CVLM) in modulating cardiovascular responses during static
      skeletal muscle contraction via altering localized glutamate and GABA levels
      (Brain Res. 977 (2003) 80-89; Neuroscience Res. 52 (2005) 21-30). In this study,
      we investigated the role of iNOS within the RVLM and CVLM on cardiovascular
      responses and glutamatergic/GABAergic neurotransmission during the exercise
      pressor reflex. Bilateral microdialysis of a selective iNOS antagonist,
      aminoguanidine (AGN; 1.0 microM), for 60 min into the RVLM attenuated increases
      in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate
      levels during a static muscle contraction. Levels of GABA within the RVLM were
      increased. After 120 min of discontinuation of the drug, MAP and HR responses and
      glutamate/GABA concentrations recovered to baseline values during a subsequent
      muscle contraction. In contrast, bilateral application of AGN (1.0 microM) into
      CVLM potentiated cardiovascular responses and glutamate concentration while
      attenuating levels of GABA during a static muscle contraction. All values
      recovered after 120 min of discontinuation of the drug. These results demonstrate
      that iNOS within the ventrolateral medulla plays an important role in modulating
      cardiovascular responses and glutamatergic/GABAergic neurotransmission that
      regulates the exercise pressor reflex.

PMID- 16650389
TI  - A monosynaptic connection between baroinhibited neurons in the RVLM and IML in
      Sprague-Dawley rats.
AB  - To date, few studies have examined the relationship between the firing rate of
      neurons in the rostral ventrolateral medulla (RVLM) and neurons in the
      intermediolateral cell column (IML) of the spinal cord. In 19 Sprague-Dawley
      rats, the relationship between 20 pairs of baroinhibited RVLM and IML units was
      analyzed by cross-correlation. Three criteria were applied before acceptance that
      the firing rate of a pair of neurons was correlated. First, at an appropriate
      latency following the firing of an RVLM neuron, as judged from previous studies
      (4-200 ms), the peak in the firing rate of an IML neuron was approximately double
      that of the averaged surrounding bin counts. Secondly, the peak grew steadily in
      the examined period. Thirdly, the peak was restricted to a 1-ms bin. With this
      approach, a correlation was found between RVLM and IML neurons in 3 pairs in all.
      In 2 pairs, a correlation was found at basal arterial pressure (AP). When AP was
      decreased using a caval snare, a correlation was demonstrated in a further pair.
      A possible potentiation of synaptic strength during hypotensive stimuli is
      discussed.

PMID- 16650390
TI  - Synthesis of spacer-equipped phosphorylated di-, tri- and tetrasaccharide
      fragments of the O-specific polysaccharide of Vibrio cholerae O139.
AB  - The synthesis of oligosaccharide fragments of the O-specific polysaccharide of
      Vibrio cholerae O139 containing a 4,6-cyclic phosphate galactose residue linked
      to GlcNAc is described. 8-Azido-3,6-dioxaoctyl 2,3,4,6-tetra-O-acetyl-beta-D
      galactopyranosyl-(1-->3)-2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D
      glucopyranoside, obtained by condensation of 2,3,4,6-tetra-O-acetyl-alpha-D
      galactopyranosyl bromide and 8-azido-3,6-dioxaoctyl 2-acetamido-4,6-O-benzylidene
      2-deoxy-beta-D-glucopyranoside, was converted to 8-azido-3,6-dioxaoctyl 3-O
      benzyl-beta-D-galactopyranosyl-(1-->3)-2-acetamido-6-O-benzyl-2-deoxy-beta-D
      glucopyranoside (6) by reductive opening of the acetal, followed by deacetylation
      and selective benzylation. Phosphorylation of 6 furnished two isomeric 4,6-cyclic
      2,2,2-trichloroethyl phosphates. Glycosylation of the (S)-phosphate with 2,4-di-O
      benzyl-3,6-dideoxy-alpha-L-xylo-hexopyranosyl bromide under halide-assisted
      conditions gave the desired tetrasaccharide, together with a trisaccharide.
      Global deprotection and reduction of the azide to an amine was effected by
      catalytic hydrogenation/hydrogenolysis to give the deprotected tetrasaccharide,
      which is functionalized for conjugation.

PMID- 16650391
TI  - Aromatic O-glycosylation.
AB  - Carbohydrates carrying an aromatic aglycon are important natural products and
      thus key synthetic targets. However, due to the electron-withdrawing properties
      of aromatic rings, phenols are difficult to glycosylate. This review covers the
      most common carbohydrate donors used for aromatic O-glycosylation (anomeric
      acetates, halides, trichloroacetimidates and thioglycosides) as well as some less
      common donors. The scope of the review is to give practical examples of aromatic
      O-glycosylations and to offer guidelines for glycosylation of typical aromatic
      residues. Anomeric acetates or trichloroacetimidates, activated under acidic
      conditions, are preferred for electron rich aromatic aglycons, while glycosyl
      halides, activated using basic conditions, are preferred for electron deficient
      aromatic residues.

PMID- 16650392
TI  - Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N
      acetyllactosamine antigens.
AB  - Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O
      linked glycan structures present in glycoproteins and glycolipids. Utilizing
      various glycosyltransferases, we developed new and efficient chemoenzymatic
      methods for the synthesis of pLNs in gram-scale. Specifically, the use of
      sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24
      blood group and tumor-associated pLN derivatives with alpha-(2-->3)- and alpha-(2
      ->6)-linked sialic acid, as well as with alpha-(1-->2)- and alpha-(1-->3)-linked
      fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer
      for further modification.

PMID- 16650393
TI  - A facile stereoselective synthesis of alpha-glycosyl ureas.
AB  - Alpha-glycosyl ureas can be synthesised directly from tetra-O-benzyl glycosyl
      azides and isocyanates, using a one-pot procedure that is simple and general in
      scope. The benzyl protecting groups are easily removed from the urea products by
      catalytic hydrogenation. The synthesised alpha-glycosyl ureas represent a new
      class of neo-glycoconjugates with the potential of being resistant towards
      carbohydrate processing enzymes.

PMID- 16650394
TI  - Inter- and intramolecular glycosylation of exo-glycals promoted by metallic Lewis
      acids.
AB  - exo-Glycosyl carbonates were employed for inter- and intramolecular glycosylation
      reactions. A number of metallic Lewis Acids and solvents were examined to enhance
      the reactivity. The optimum conditions were found to be the use of AlCl3 in 1
      nitropropane. The method was demonstrated to be useful for the intermolecular
      glycosyl transfer of several nucleophiles, including simple alcohols, sugars, and
      amino acid derivatives; however, intramolecular glycosylations were not
      successful.

PMID- 16650395
TI  - Synthesis of hexa- to tridecasaccharides related to Shigella dysenteriae type 1
      for incorporation in experimental vaccines.
AB  - Hexa- to tridecasaccharides corresponding to the O-specific polysaccharide (O-SP)
      of the Gram-negative bacterium Shigella dysenteriae type 1 were synthesized in
      solution phase. The syntheses utilized tetra-, octa-, and dodecasaccharide
      intermediates that represent one to three contiguous tetrasaccharide repeating
      units of the O-SP [Synlett2003, 743]. These compounds were glycosylated with mono
      , di-, and trisaccharide trichloroacetamidates, which were synthesized in this
      study. The excellent stereodirecting effect of 4,6-O-benzophenone ketals in
      glycosylation reactions of 2-azido-2-deoxy-glucopyranosyl donors was
      demonstrated. The free oligosaccharides were characterized by 1H and 13C NMR
      spectroscopy and by high-resolution mass spectrometry. The oligosaccharides
      described herein contain the 5-(methoxycarbonyl)pentyl aglycon for eventual
      attachment to immunogenic carriers using a recently published protocol [J. Org.
      Chem.2005, 70, 6987].

PMID- 16650396
TI  - New urinary EPO drug testing method using two-dimensional gel electrophoresis.

PMID- 16650397
TI  - Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic
      breast cancer patients.
AB  - BACKGROUND: The role of circulating TGF-beta(1) in prognosis of breast cancer
      (BC) was investigated with an intention to define TGF-beta(1)-dependent high risk
      and low risk subsets of patients. METHODS: Fifty three BC patients of all
      clinical stages and 37 healthy donors (HD) were analyzed for plasma TGF-beta(1)
      by the TbetaRII receptor-based Quantikine TGF-beta(1) ELISA kit. RESULTS: The
      plasma TGF-beta(1) level of Stage I/II disease (median: 0.94 ng/ml; n=10))
      remained close to HD (median: 1.30 ng/ml; n=37; p>0.1). In contrast, Stage III/IV
      disease (median: 2.34 ng/ml; n=43) exhibited highly significant TGF-beta(1)
      elevation (p<0.001) relative to HD. Further analysis revealed that TGF-beta(1)
      increase was predominantly attributed to Stage IV, metastatic disease patients
      (Q3=4.23 ng/ml) rather than to the group Stage III/IV (Q3=3.58 ng/ml). Using the
      plasma TGF-beta(1) concentration of 3.00 ng/ml as the cut-off value, two
      subgroups of patients were formed. Overall 2-year survival of the first subgroup,
      having elevated plasma TGF-beta(1) (>3.00 ng/ml; n=10), was 10%. This was
      significantly decreased (p<0.05) compared to 52% survival observed for the second
      subgroup of patients with plasma TGFbeta(1) values close to HD (<3.00 ng/ml,
      n=19). CONCLUSION: We have performed a pilot study to determine the relationship
      between overall survival and TGF-beta(1) concentration in the blood of metastatic
      breast cancer patients. The survival was significantly reduced in the patients
      with elevated plasma TGF-beta(1) levels compared to that of the patients with
      plasma TGF-beta(1) levels close to normal. We propose that plasma TGF-beta(1)
      concentration may be a new tumour marker attributed to the presence of metastatic
      BC cells that may be used in selection of metastatic BC patients with poor
      prognosis.

PMID- 16650398
TI  - Determination of glutathione in hemolysed erythrocyte with amperometric sensor
      based on TTF-TCNQ.
AB  - BACKGROUND: GSH has a relevant role in human metabolism as an indicator of
      disease risks. An amperometric sensor for glutathione (GSH) determination is
      described as an alternative method featuring simple construction procedure and
      short time analysis. METHOD: The developed sensor was used to determine
      glutathione at low potential using a TTF-TCNQ complex. RESULTS: The sensor
      exhibits a linear response range from 5 to 340 micromol/l under applied potential
      of 200 mV vs. SCE. The sensitivity and detection limit were 90.1 microA l/mmol
      cm(2) and 0.3 micromol/l, respectively. CONCLUSION: When the sensor was tested in
      hemolysed erythrocyte samples for GSH determination, a good correlation in
      results was observed between the sensor and the spectrophotometric method. The
      sensor showed recovery values between 98% and 102%.

PMID- 16650399
TI  - Learning phonetic categories by tracking movements.
AB  - We explore in this study how infants may derive phonetic categories from adult
      input that are highly variable. Neural networks in the form of self-organizing
      maps (SOMs; ) were used to simulate unsupervised learning of Mandarin tones. In
      Simulation 1, we trained the SOMs with syllable-sized continuous F(0) contours,
      produced by multiple speakers in connected speech, and with the corresponding
      velocity profiles (D1). No attempt was made to reduce the large amount of
      variability in the input or to add to the input any abstract features such as
      height and slope of the F(0) contours. In the testing phase, reasonably high
      categorization rate was achieved with F(0) profiles, but D1 profiles yielded
      almost perfect categorization of the four tones. Close inspection of the learned
      prototypical D1 profile clusters revealed that they had effectively eliminated
      surface variability and directly reflected articulatory movements toward the
      underlying targets of the four tones as proposed by . Additional simulations
      indicated that a further learning step was possible through which D1 prototypes
      with one-to-one correspondence to the tones were derived from the prototype
      clusters learned in Simulation 1. Implications of these findings for theories of
      language acquisition, speech perception and speech production are discussed.

PMID- 16650400
TI  - A set of amino acids found to occur more frequently in human and fly than in
      plant and yeast proteomes consists of non-essential amino acids.
AB  - We investigated the hypothesis that essential amino acids are being replaced in
      proteins by non-essential amino acids. We compared the amino acid composition in
      human, worm and fly proteomes, organisms that cannot synthesize all amino acids,
      with the amino acids of the proteomes of plant, bakers yeast and budding yeast,
      which are capable of synthesizing them. The analysis covered 460,737 proteins
      (212,197,907 amino acids). The data suggest a bias towards the usage of non
      essential amino acids (mostly the set GAPQC) by metazoan organisms, except for
      the worm, a Pseudocoelomata. Our results support the hypothesis that non
      essential amino acids have been substituting essential ones in the Coelomata.

PMID- 16650401
TI  - Focal adhesions: what's new inside.
AB  - The cytoplasmic side of focal adhesions is comprised of large molecular complexes
      that link transmembrane receptors, such as integrins, to the actin cytoskeleton
      and mediate signals modulating cell attachment, migration, proliferation,
      differentiation, and gene expression. These complexes are heterogeneous and
      dynamic structures that are apparent targets of regulatory signals that control
      the function of focal adhesions. Recent studies using genetic approaches in
      invertebrate and vertebrate systems have begun to reveal the structure and
      function of these complexes in vivo.

PMID- 16650402
TI  - Possible involvement of cholinergic and opioid receptor mechanisms in fluoxetine
      mediated antinociception response in streptozotocin-induced diabetic mice.
AB  - Clinical and experimental studies have been reported that antidepressant drugs
      can be used as co-analgesics in the management of neuropathic pain. However, the
      mechanism through which they alleviate pain still remains unclear. The aim of the
      present study was to investigate the possible mechanism of action of fluoxetine
      induced antinociceptive effect in streptozotocin-induced diabetic mice,
      especially the involvement of non-serotonergic neurotransmitters and their
      receptors. Diabetes was induced in male Laka mice with a single intraperitoneal
      injection of streptozotocin (200 mg/kg). Four weeks after streptozotocin,
      diabetic mice were tested for pain responses in the tail-immersion and hot-plate
      assays. Diabetic mice exhibited significant hyperalgesia as compared with control
      mice. Fluoxetine (10 and 20 mg/kg, i.p) injected into diabetic mice produced an
      antinociceptive effect in both tail-immersion and hot-plate assays. The
      antinociceptive effect of fluoxetine in diabetic mice was significantly lower as
      compared with that in control mice. Pretreatment with a muscarinic receptor
      antagonist, atropine (2 and 5 mg/kg, i.p) and an opioid receptor antagonist,
      naloxone (2 and 5 mg/kg, i.p), but not the alpha(2)-adrenoreceptor antagonist,
      yohimbine (2 and 5 mg/kg, i.p) reversed the antinociceptive effect of fluoxetine
      (20 mg/kg). These results suggest that apart from serotonin pathway, muscarinic
      and opioid receptors also participate in fluoxetine-induced antinociception in
      diabetic neuropathic pain.

PMID- 16650403
TI  - The calpain inhibitor, A-705253, corrects penile nitrergic nerve dysfunction in
      diabetic mice.
AB  - Calpains, a superfamily of Ca(2+)-activated proteases, are associated with an
      array of physiological and pathological events, including susceptibility to
      diabetes. Recently, increased calpain activity has been linked to reduced
      endothelium-derived nitric oxide-mediated vasodilatation in diabetes. However, a
      similar mechanism for neuronal-derived nitric oxide has not been examined. Thus,
      the aim was to investigate effects of the calpain inhibitor A-705253, N-(1-benzyl
      2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethyl-aminomethylphenyl)ethen-1-yl]benzamide,
      on nitrergic neurovascular function in diabetic mice. Diabetes was induced by
      streptozotocin; duration was 6 weeks. Intervention A-705253 treatment (30
      mg/kg/day) was given for 2 weeks following 4 weeks of untreated diabetes. After 6
      weeks of diabetes, corpus cavernosa were isolated in organ baths for measurement
      of agonist- and electrical stimulation-evoked smooth muscle tensions. Adrenergic
      nerve- and phenylephrine-mediated contractions were not altered by diabetes or
      calpain inhibition. In contrast, maximum nitrergic nerve-mediated relaxation of
      phenylephrine-precontracted cavernosum was approximately 29% reduced by diabetes
      (P<0.001). This neurological deficit was 66% corrected by A-705253 treatment
      (P<0.05). Maximum nitric oxide-mediated endothelium-dependent relaxation to
      acetylcholine was attenuated approximately 39% by diabetes (P<0.01). Similarly,
      maximum endothelium-independent relaxation to the nitric oxide donor, sodium
      nitroprusside, was blunted approximately 23% by diabetes (P<0.001). A-705253
      treatment partially improved endothelium-dependent relaxation to acetylcholine
      but had no effect on the deficit in response to nitroprusside. The data suggest
      that calpain contributes to the aetiology of diabetic nitrergic autonomic
      neuropathy and endothelial dysfunction, which may provide a novel therapeutic
      target for neurovascular complications.

PMID- 16650404
TI  - Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation
      of ERK1/2 proteins.
AB  - In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial
      smooth muscle cells are upregulated. The present study revealed that organ
      culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor
      mediated contraction paralleled with increase in the receptor mRNA and protein
      expressions. The endothelin ET(B) receptor-mediated contraction was associated
      with increase in phosphorylation of extracellular regulation kinase 1 and 2
      (ERK1/2) proteins and elevated levels of intracellular calcium. The elevation
      curve of intracellular calcium consisted of two phases: one rapid and one
      sustained. Inhibition of ERK1/2 phosphorylation by SB386023 or blockage of
      calcium channels by nifedipine significantly reduced the endothelin ET(B)
      receptor-mediated contraction (P<0.05) and decreased the sustained phase of
      intracellular calcium level, but not the rapid phase. Thus, phosphorylation of
      ERK1/2 proteins and elevation of intracellular calcium level are required for
      endothelin ET(B) receptor-mediated contraction in rat mesenteric artery.

PMID- 16650405
TI  - Histamine release, an undesired effect of thrombin inhibitors with basic
      character, is mediated through direct activation of G(i) proteins.
AB  - The common structural feature of LK direct thrombin inhibitors is a strong basic
      group attached to the azaphenylalanine scaffold, which is important for the
      appropriate interaction at the thrombin active site. Our previous results have
      shown that this basic group could be responsible for a reduction of tracheal air
      flow and a fall of mean arterial pressure in anaesthetized rats, an undesired
      effect of direct thrombin inhibitors which correlated with their ability to
      release histamine from mast cells. In the present study, we investigated the
      mechanism of LK direct thrombin inhibitors-induced histamine release from rat
      peritoneal mast cells. We demonstrated that thrombin inhibitors with basic
      character (LK-732, LK-639 and LK-6063) provoked release of histamine from mast
      cells, while less basic analogs (LK-658, LK-633 and LK-6062) had no effect.
      Histamine released by LK-732 and LK-639 was suppressed by removal of sialic acid
      residues by neuraminidase and by pertussis toxin, an inhibitor of G(i) protein
      activity. Additional demonstration that G proteins are the targets of LK-732 and
      LK-639 was provided by the increase of GTPgammaS binding rate to G proteins in
      rat brain cortical membranes. Our results indicate that basic direct thrombin
      inhibitors LK-732 and LK-639 provoke release of histamine from mast cells by
      direct activation of G(i) proteins through the similar biochemical pathway as
      basic secretagogues.

PMID- 16650406
TI  - Inhibition of MHC class II gene expression in uveal melanoma cells is due to
      methylation of the CIITA gene or an upstream activator.
AB  - Most cells with an intact interferon-gamma receptor and signaling pathway are
      able to express MHC class II molecules when treated with cytokines such as
      interferon-gamma and tumor necrosis factor-a. Interestingly, primary uveal
      melanocytes and most ocular melanoma cells are resistant to interferon-gamma
      mediated induction of class II MHC genes. This unusual phenotype is hypothesized
      to be germane to the immune-privileged status to the eye. Via a series of
      experiments, we have probed the molecular basis of this class II MHC resistant
      phenotype. We have analyzed the methylation status of the gene encoding the class
      II transactivator (CIITA), and asked whether treatment of class II MHC resistant
      ocular melanoma cells with the demethylating agent 5'-azacytidine can restore
      interferon-gamma inducibility of these class II MHC genes in these cells. The
      data obtained suggest that the specific blockade in cytokine-induced class II MHC
      gene expression is due to a suppression of the gene encoding the class II
      transactivator (CIITA). Treatment with 5' azacytidine restores the ability of
      these cells to express class II MHC genes upon interferon-gamma treatment. Whilst
      this is reminiscent of what occurs in another immune-privileged tissue--the
      placental trophoblast--we show here that silencing of the CIITA gene in uveal
      melanocytes either involves methylation of distinct nucleotides from those
      detected in trophoblasts, or involves an upstream activator of CIITA gene
      expression.

PMID- 16650407
TI  - The chaperone function of cyclophilin 40 maps to a cleft between the prolyl
      isomerase and tetratricopeptide repeat domains.
AB  - Cyclophilin 40 (CyP40), an immunophilin cochaperone present in steroid receptor
      Hsp90 complexes, contains an N-terminal peptidylprolyl isomerase (PPIase) domain
      separated from a C-terminal Hsp90-binding tetratricopeptide repeat (TPR) domain
      by a 30-residue linker. To map CyP40 chaperone function, CyP40 deletion mutants
      were prepared and analysed for chaperone activity. CyP40 fragments containing the
      PPIase domain plus linker or the linker region and the adjoining TPR domain
      retained chaperone activity, whilst individually, the catalytic and TPR domains
      were devoid of chaperoning ability. CyP40 chaperone function then, is localized
      within the linker that forms a binding cleft with potential to accommodate non
      native substrates.

PMID- 16650408
TI  - Activated leukocyte cell adhesion molecule is a component of the endothelial
      junction involved in transendothelial monocyte migration.
AB  - Transendothelial leukocyte migration is a major aspect of the innate immune
      response. It is essential in repair and regeneration of damaged tissues and is
      regulated by multiple cell adhesion molecules (CAMs) including members of the
      immunoglobulin (Ig) superfamily. Activated leukocyte cell adhesion molecule
      (ALCAM/CD166) is an Ig CAM expressed by activated monocytes and endothelial
      cells. Hitherto, the functional relevance of ALCAM expression by endothelial
      cells and activated monocytes remained unknown. In this report, we demonstrate
      soluble recombinant human ALCAM significantly inhibited the rate of
      transendothelial migration of monocyte cell lines. Direct involvement of ALCAM in
      transendothelial migration was evident from the robust inhibition of this process
      by ALCAM blocking antibodies. However, soluble recombinant ALCAM had no impact on
      monocyte migration or adhesion to endothelium. Localization of ALCAM specifically
      at cell-cell junctions in endothelial cells supported its role in
      transendothelial migration. This study is the first to localize ALCAM to
      endothelial cell junctions and demonstrate a functional relevance for co
      expression of ALCAM by activated monocytes and endothelial cells.

PMID- 16650409
TI  - Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin
      and Toll-like receptor 5.
AB  - Toll-like receptors (TLR) detect pathogen-associated molecular patterns (PAMP)
      and play a crucial role in triggering immunity. Due to their large surfaces in
      direct contact with the environment, mucosal tissues are the major sites of PAMP
      TLR signalling. How innate and adaptive immunity are triggered through flagellin
      TLR5 interaction is the main focus of the review. In view of recent reports on
      genetic polymorphism, we will summarize the impact of TLR5 on the susceptibility
      to mucosal infections and on various immuno-pathologies. Finally, the
      contribution of TLRs in the induction and maintenance of mucosal homeostasis and
      commensal discrimination is discussed.

PMID- 16650410
TI  - Leader sequence of a plant ribosomal protein gene with complementarity to the 18S
      rRNA triggers in vitro cap-independent translation.
AB  - Cap-independent translation (CIT) occurs at the leader sequences of uncapped
      plant viral RNAs, but also at a number of normally capped cellular mRNAs and has
      been correlated with sequence complementarity to 18S rRNA. The ribosomal protein
      S18 (RPS18) is a component of the small ribosomal subunit and is encoded by three
      gene copies (A, B, and C) in the Arabidopsis thaliana genome. The RPS18C mRNA was
      most abundant and contained a short 5' untranslated region of 84 bp that is
      complementary to a novel putative interaction site at the 3' end of the 18S rRNA.
      The RPS18C leader mediated CIT as demonstrated by dicistronic constructs
      consisting of luciferase and chloramphenicol acetyl transferase reporter genes in
      an in vitro wheat germ extract system. CIT was rapidly inhibited upon addition of
      an oligonucleotide that competed for the 18S rRNA site complementary to the
      RPS18C leader and interfered with polysome assembly at the transcript.

PMID- 16650411
TI  - Bacterial entry into cells: a role for the endocytic machinery.
AB  - Increasing evidence indicates that pathogens have evolved highly efficient
      strategies to induce their internalization within host cells. Viruses and
      bacteria express and expose on their surface, molecules that mimic endogenous
      ligands to cell receptors, thereby inducing specific intracellular signalling
      cascades. More recently it has become clear that, as most viruses, bacteria can
      enter cells via the clathrin-mediated pathway, indicating a key role for
      endocytosis in pathogens entry into cells. Here we review the pathways followed
      by Listeria monocytogenes to enter into non-phagocytic cells, as a model for the
      subversion of cellular functions to induce pathogens internalization.

PMID- 16650412
TI  - Molecular imprinted polymer with cloned bacterial protein template enriches
      authentic target in cell extract.
AB  - Here we describe a new method for preparing a protein-imprinted polymer with a
      cloned bacterial protein template, which recognizes/adsorbs authentic target
      protein present at a relatively low level in cell extract. In this work, cloned
      pig cyclophilin 18 (pCyP18) was used as a template. The template protein was
      selectively assembled with memory molecules from their library, which consists of
      numerous limited length polymer chains with randomly distributed recognition
      sites and immobilizing sites. These assemblies of protein and memory molecules
      were adsorbed by porous polymeric beads and immobilized by cross-linking
      polymerization. After removing the template, binding sites that were
      complementary to the target protein in size, shape and the position of
      recognition groups were exposed, and their confirmation was preserved by the
      cross-linked structure. The synthesized imprinted polymer was used to adsorb
      authentic pCyP18 from cell extract, and its proportional content was enriched 300
      times.

PMID- 16650413
TI  - HCMV infection attenuates hydrogen peroxide induced endothelial apoptosis--
      involvement of ERK pathway.
AB  - Human cytomegalovirus (HCMV) exerts anti-apoptotic effect during early stage of
      infection, which provides HCMV time for propagation. We investigated pathways
      mediating the resistance to H(2)O(2)-induced cell death - a self-defense
      mechanism to remove infected cells. We found that human aortic endothelial cells
      (HAECs) infected with VHL/E strain of HCMV during first 3 days were resistant to
      H(2)O(2) (0-2 mM) induced apoptosis. This anti-apoptotic effect may be mediated
      by the upregulation of Bcl-2, an anti-apoptotic protein through the activation
      pro-survival pathway extracellular signal regulated kinase (ERK). Through this
      mechanism, HCMV is able to propagate and causes endothelial dysfunction, hence
      vascular disease.

PMID- 16650414
TI  - Follicular fluid levels of inhibin A, inhibin B, and activin A levels reflect
      changes in follicle size but are not independent markers of the oocyte's ability
      to fertilize.
AB  - OBJECTIVE: To investigate the biochemical relationship between follicular/oocyte
      maturity and follicular inhibins and activin levels. DESIGN: Prospective study.
      SETTING: Research laboratory in university hospital. PATIENT(S): Thirty-five
      women undertook IVF/ICSI program. INTERVENTION(S): Individual follicular fluid
      aspirations, oocyte isolation, follicular fluid storage. MAIN OUTCOME MEASURE(S):
      Inhibin A, inhibin B, and activin A concentrations, oocyte retrieval, and
      fertility outcome. RESULT(S): Inhibin A, inhibin B, and activin A concentrations
      varied from 7.9 to 436 ng/mL, 9.7 to 786 ng/mL, and 1.7 to 267.9 ng/mL,
      respectively. There was no change of inhibin A concentrations, whereas inhibin B
      and activin A concentrations dropped dramatically as the follicles enlarged.
      Total follicular content of inhibin A and activin A increased, and inhibin B
      remained constant. Both inhibin A and inhibin B levels were significantly higher
      in those follicles from which an oocyte could be recovered, but they did not
      differ with respect to subsequent oocyte fertilization. CONCLUSION(S): Inhibin A
      is actively produced throughout follicular growth to retain a set concentration.
      In contrast, inhibin B appears not to be actively produced, and the concentration
      drops as follicles enlarge. Activin A concentrations also decrease, but there is
      some extra synthesis. Higher levels of inhibin A and B are associated with oocyte
      presence but not with fertilization rates.

PMID- 16650415
TI  - Clinical and laboratory characteristics of adolescents with both polycystic ovary
      disease and anorexia nervosa.
AB  - In girls evaluated for anorexia nervosa (AN), coexistence of polycystic ovary
      disease (PCOS) was found when menstrual irregularities existed before weight
      loss, cessation of menses occurred at a relatively elevated body mass index, and
      LH and estrogen levels were elevated compared with adolescents with AN alone. In
      adolescents with PCOS + AN weight gain beyond recommended weight should not be
      advised.

PMID- 16650416
TI  - The clomiphene citrate challenge test versus the exogenous follicle-stimulating
      hormone ovarian reserve test as a single test for identification of low
      responders and hyperresponders to in vitro fertilization.
AB  - OBJECTIVE: This study was designed to compare the exogenous FSH ovarian reserve
      test (EFORT) versus the clomiphene citrate challenge test (CCCT), basal FSH, and
      basal inhibin B, with respect to their ability to predict poor and/or
      hyperresponders in an IVF population. DESIGN: Prospective randomized controlled
      trial. SETTING: Fertility center of a university hospital. PATIENT(S): One
      hundred ten patients undergoing their first IVF cycle, randomized into two
      groups. INTERVENTION(S): Fifty-six patients underwent a CCCT, and 54 patients
      underwent an EFORT. In all patients, the test was followed by an IVF treatment.
      MAIN OUTCOME MEASURE(S): Ovarian response, expressed by the total number of
      retrieved oocytes. RESULT(S): Univariate logistic regression showed that the best
      predictor for poor response is the CCCT (area under receiver operator
      characteristic curve [ROC-AUC] = 0.87), with maximal accuracy of 0.89. Multiple
      logistic regression analysis did not produce a better model in terms of improving
      the prediction of poor response. For hyper response, univariate logistic
      regression showed that the best predictor is the inhibin B increment in the EFORT
      (ROC-AUC = 0.92) but with a low maximal accuracy of 0.78. Again, multiple
      logistic regression analysis did not produce a better model in terms of
      predicting hyper response. CONCLUSION(S): Our study, the first which compares the
      CCCT with the EFORT for the prediction of poor and hyperresponders, shows that
      the CCCT is superior for identification of low responders. The EFORT (inhibin B
      increment) is superior for prediction of hyper response at the cost of a high
      rate of false positives. Neither of the two tests seems adequate to act alone for
      identification of both poor and hyperresponders.

PMID- 16650417
TI  - Family size in women with polycystic ovary syndrome.
AB  - Given that polycystic ovary syndrome (PCOS) is associated with oligo-ovulatory
      infertility and is an inherited trait, we hypothesized that the families of
      patients with PCOS are smaller than those of matched controls. However, our study
      of 106 white patients with PCOS, ages 18-45, and 53 healthy eumenorrheic
      nonhirsute white controls did not indicate a difference in family size between
      the groups; these results have important implications for the design of
      prospective studies of the heritability and genetics of PCOS.

PMID- 16650418
TI  - Plasma metastin levels are negatively correlated with insulin resistance and free
      androgens in women with polycystic ovary syndrome.
AB  - OBJECTIVE: This study was designed to: [1] measure, for the first time, metastin
      (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition
      associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate
      the possible correlations between metastin and PCOS-related reproductive and
      metabolic disturbances. DESIGN: Clinical study. SETTING: University hospital.
      PATIENT(S): Twenty-eight obese and overweight (body mass index [BMI] >25 kg/m2)
      women with PCOS, 28 normal weight (BMI <25 kg/m2) women with the syndrome, and 13
      obese and overweight controls (ovulatory women without clinical or biochemical
      hyperandrogenemia) were selected. INTERVENTION(S): Blood samples were collected
      between day 3 and day 6 of a spontaneous bleeding episode in the PCOS groups and
      a menstrual cycle of the controls, at 9:00 AM, after an overnight fast. MAIN
      OUTCOME MEASURE(S): Circulating levels of LH, FSH, PRL, T, Delta4-androstenedione
      (A), DHEAS, 17alpha-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose,
      and metastin were measured. RESULT(S): Both normal weight women with PCOS and
      obese controls were less insulin resistant and had significantly higher metastin
      levels, compared to obese and overweight women with the syndrome. Plasma
      kisspeptin levels were negatively correlated with BMI, free androgen index, and
      indices of insulin resistance. CONCLUSION(S): These results indicate that
      metastin is negatively associated with free androgen levels. The PCOS-associated
      insulin resistance and consequent hyperinsulinemia probably contribute to this
      effect by [1] stimulating androgen synthesis by the polycystic ovary (PCO) and
      [2] suppressing SHBG production in the liver.

PMID- 16650419
TI  - Mullerian anomalies, hearing loss, and connexin 26 mutations.
AB  - In a study of the possible inter-relationship among mullerian anomalies, hearing
      loss, and connexin 26 mutations, we evaluated all women in whom mullerian
      anomalies were diagnosed on hysterosalpingography during a 6-year period (n =
      24/519). Audiometric testing revealed five (22.7%) with unrecognized
      sensorineural hearing loss; however, on genetic evaluation, none harbored a
      connexin 26 mutation.

PMID- 16650420
TI  - Contrast infusion sonography to assess microinsert placement and tubal occlusion
      after Essure.
AB  - OBJECTIVE: To develop a technique for contrast infusion sonography and assess the
      possible use in determining microinsert placement and tubal status after Essure
      sterilization. DESIGN: Techniques and instrumentation. SETTING: Healthy women in
      an academic multispecialty group. PATIENT(S): Ten women desiring permanent
      sterilization who have recently undergone Essure hysteroscopic sterilization.
      INTERVENTION(S): Contrast infusion sonography, an adaptation of hysterosalpingo
      contrast sonography, performed at 3-23 weeks after Essure placement. MAIN OUTCOME
      MEASURE(S): To determine how readily tubal status and microinsert location could
      be assessed with this adaptation of hysterosalpingo contrast sonography.
      RESULT(S): All microinserts were readily identified and tubal status was assessed
      by identification or absence of real-time contrast agent flow. CONCLUSION(S):
      This technique is very promising and could represent a convenient alternative to
      hysterosalpingogram (HSG) 3 months after Essure placement.

PMID- 16650421
TI  - Comparison of success rates in the medical management of ectopic pregnancy with
      single-dose and multiple-dose administration of methotrexate: a prospective,
      randomized clinical trial.
AB  - OBJECTIVE: To assess whether success rate differs in single-dose versus multiple
      dose administration of methotrexate (MTX) in medical management of unruptured
      ectopic pregnancies. DESIGN: Prospective randomized clinical trial. SETTING:
      Tertiary university hospital. PATIENT(S): The study population included 108
      patients presenting with unruptured ectopic pregnancies who fulfilled the
      criteria for medical management. INTERVENTION(S): A single dose (study group) or
      multiple doses (control group) of MTX were administered IM. MAIN OUTCOME
      MEASURE(S): Success rate of medical management in each group. RESULT(S): Of the
      54 patients on the single-dose protocol, treatment was considered successful in
      48 patients (88.9%). Of the 54 patients on the multiple-dose protocol, 50
      participants responded to the treatment (92.6%). The difference between success
      rates in the two groups was not statistically significant (P=.7; odds ratio 0.64;
      95% confidence interval 0.17-2.4). In the single-dose and multiple-dose groups,
      15 (27.8%) and 20 (37%) patients, respectively, had complications (P=.3).
      CONCLUSION(S): The results of our study showed that single-dose treatment with
      MTX could be as successful as multiple doses. The incidence of complications did
      not differ between the two groups. It appears that single-dose treatment could be
      the first line of treatment in selected patients.

PMID- 16650422
TI  - Congenital malformations among 911 newborns conceived after infertility treatment
      with letrozole or clomiphene citrate.
AB  - OBJECTIVE: To evaluate the incidence of congenital malformations among offspring
      of mothers who conceived with clomiphene citrate (CC) or with letrozole treatment
      for infertility. DESIGN: Retrospective study. SETTING: 5 fertility centers in
      Canada. PATIENTS: 911 newborns from women who conceived following CC or letrozole
      treatment. INTERVENTIONS: Examination of medical files of both mother and
      newborn, and cross-checked with the parents by telephone calls. MAIN OUTCOME
      MEASURES: Identified major and minor congenital malformations, birth weight, age
      of the mother, and type of treatment that led to the conception. RESULTS:
      Overall, congenital malformations and chromosomal abnormalities were found in 14
      of 514 newborns in the letrozole group (2.4%) and in 19 of 397 newborns in the CC
      group (4.8%). The major malformation rate in the letrozole group was 1.2% (6/514)
      and in the CC group was 3.0% (12/397). One newborn in the letrozole group was
      found to have a ventricular septal defect (0.2%) compared to 4 newborns in the CC
      group (1.0%). In addition, the rate of all congenital cardiac anomalies was
      significantly higher (P: 0.02) in the CC group (1.8%) compared to the letrozole
      group (0.2%). CONCLUSION: There was no difference in the overall rates of major
      and minor congenital malformations among newborns from mothers who conceived
      after letrozole or CC treatments. However, it appears that congenital cardiac
      anomaly is less frequent in the letrozole group. The concern that letrozole use
      for ovulation induction could be teratogenic is unfounded based on our data.

PMID- 16650423
TI  - Analysis of fecal glucocorticoids in the North Atlantic right whale (Eubalaena
      glacialis).
AB  - Very little is known about the endocrinology of the baleen whales. The highly
      endangered North Atlantic right whale (NARW; Eubalaena glacialis) is a good model
      species, because most NARW individuals are photo-identified with known histories.
      We used an 125I corticosterone assay, shown to reliably measure cortisol
      metabolites, to determine glucocorticoid metabolite concentrations in 177 NARW
      fecal samples collected between 1999-2004 in the Bay of Fundy, Canada. Fecal
      glucocorticoid metabolite concentrations varied significantly with sex and
      reproductive category, being highest in pregnant females (mean +/-SE: 238.14+/
      74.37 ng/g) and mature males (71.6+/-11.36), intermediate in lactating females
      (39.33+/-5.82), and lower in non-reproducing females (23.11+/-4.25) and immature
      males (34.33+/-5.01) and females (14.0+/-0.41). One case also suggests that
      glucocorticoids rise markedly in response to severe entanglement in fishing
      lines. Whales with fecal glucocorticoid content over 100 ng/g (termed "high-cort"
      samples) were rare, and included most pregnant females, some mature males, a
      fatally entangled whale, and several very young animals. Glucocorticoid
      concentrations were highly correlated with androgen concentrations in males and
      pregnant females. We analyzed the elution profiles of glucocorticoid and androgen
      metabolites in 13 samples with high-performance liquid chromatography (HPLC) to
      determine the extent to which androgen metabolites cross-react with our
      glucocorticoid assay. Males, pregnant females, non-pregnant females, and "high
      cort" whales each had distinctly different immunoreactive HPLC profiles of
      glucocorticoid and androgen metabolites. A major glucocorticoid metabolite was
      prominent in all "high-cort" whales including the fatally entangled whale. The
      major fecal androgen was not testosterone but was instead a more nonpolar steroid
      (possibly dihydrotestosterone), which may be diagnostic of males. Androgen
      metabolites showed only minor cross-reactivity to our glucocorticoid assay,
      having a slight influence on glucocorticoid results in particular individuals. We
      conclude that fecal glucocorticoid analysis appears to be a useful measure of
      adrenal activity and reproductive condition for NARW.

PMID- 16650424
TI  - Simultaneous pituitary-gonadal recrudescence in two Corsican populations of male
      blue tits with asynchronous breeding dates.
AB  - Animal populations living in geographically variable environments respond to
      different selection pressures. The adaptive character of the responses to
      environmental information determines the degree of synchrony of the breeding
      period with local optimal conditions. An example is provided by two populations
      of Mediterranean blue tits (Parus caeruleus) in Corsica, breeding in different
      habitats, with a 1-month difference in the onset of egg laying. This difference
      in the onset of lay is supposed to be adaptive because, although chicks from both
      populations are raised mostly on caterpillars, the timing of the appearance of
      caterpillars is earlier for populations of tits associated with deciduous oak
      trees than those associated with evergreen oak trees. Here, we show that, despite
      the difference in the timing of egg laying, males from these two populations
      start seasonal hypothalamo-hypophysial-testicular development at approximately
      the same time, in late winter. Specifically, the vernal recrudescence of brain
      GnRH-I perikarya and fibers, testes volume and song activity began around the
      same dates and proceeded at the same pace in late winter in both populations.
      Plasma testosterone and LH levels displayed seasonal variations that were shifted
      by less than 2 weeks compared to the 1-month difference in egg laying periods. We
      hypothesize that the strong selection pressures on these two populations to adapt
      the timing of their breeding seasons to their local environment may have acted
      mostly on the female egg laying dates, and not so much on the initiation and rate
      of seasonal recrudescence of the hypothalamo-hypophysial-testicular activity in
      males.

PMID- 16650425
TI  - A study of nurses' spiritual intelligence: a cross-sectional questionnaire
      survey.
AB  - BACKGROUND: Nurse's spiritual well-being may assure a positive attitude toward
      spiritual care, and assist patients in overcoming spiritual distress.
      Spirituality is often related to one's belief system. Spirituality on the part of
      nurses is yet largely unheard of in a society with materialism which is one of
      the most destructive belief systems on the world. OBJECTIVES: The objective of
      the study was to explore the profile of spiritual intelligence among nurses, and
      to examine the effect of religions on nurses' spiritual intelligence in China.
      DESIGN: This is a cross-sectional descriptive and inferential designed study.
      SETTINGS: The study was carried out in a medical center in China. Subjects were
      widely distributed, throughout seven provinces, with 16 hospital settings.
      PARTICIPANTS: A total of 130 registered hospital nurses, who were taking part in
      a 3-day, national nursing quality conference held by the target medical center in
      China, were recruited by convenience sampling. METHODS: Wolman's (2001) four
      point Likert-type Psycho-Matrix Spirituality Inventroy (PSI) was distributed
      collaboratively during the period of the conference. Upon receiving oral approval
      from nursing administrators, the author ensured that subjects' responses would
      remain confidential and that filling out the questionnaire was to be construed as
      willingness to participate in this study. RESULTS: 1. The majority of nurses
      (90%) tended to experience numerous instances of physical emotional pain and
      suffering throughout life. 2. Among the 130 subjects, only seven nurses clearly
      specified their religions, and religious beliefs accounted for most of the
      variance in the criterion variable in the study. CONCLUSIONS: Exploring nurses'
      spiritual profiles, especially for those who seem to be unfamiliar with spiritual
      matters, is a starting point on the journey to delivering spiritual care. Chinese
      nurses' spiritual intelligence is only to be excavated. The study draws attention
      to the diverse culture of the nurses' concepts of spirituality, which is
      fundamental to the delivery of truly holistic care of humans in a multi-faith
      society.

PMID- 16650426
TI  - Parasite risk factors for stunting in grade 5 students in a community of extreme
      poverty in Peru.
AB  - Malnutrition in school-age children is common in developing countries and
      includes both stunting and underweight. Stunting, which represents a chronic
      state of nutritional stress, leads to adverse health, educational and cognitive
      effects. Although much research is focused on preschool-age children, recent
      studies show both the high prevalence of stunting and the effectiveness of
      interventions in school-age children. The objectives of the current study were to
      determine the risk factors for stunting only, and stunting and underweight. A
      survey was conducted in 1074 grade 5 children (mean age 10 years) from 17 schools
      in Belen, Peru, a community of extreme poverty. Prevalence of underweight and
      stunting were 10.5 and 34.5%, respectively, co-prevalence was 9.3%. Based on
      multivariable logistic regression analyses, significant independent risk factors
      (odds ratio: OR) for stunting and underweight were: age (per 1 year increment)
      (OR=1.55; 95% confidence interval (CI): 1.33, 1.81); diarrhoea in the last week
      (OR=1.96; 95% CI: 1.17, 3.29) and hookworm infection (OR=1.74; 95% CI: 1.05,
      2.86). Significant independent risk factors for stunting only were: age (per 1
      year increment) (OR=1.51; 95% CI: 1.35, 1.70); anaemia (OR=1.98; 95% CI: 1.26,
      3.11); and moderate and heavy Trichuris and Ascaris co-infection (OR=1.95; 95%
      CI: 1.35, 2.82). Our results indicate a high prevalence of stunting, in addition
      to other adverse health indicators, in the study population. Due to the
      interrelation between many of these health and nutrition problems, interventions
      at both the school and community levels, including de-worming, feeding programs
      and health and hygiene education, are needed to reduce malnutrition in this and
      other similar populations living in conditions of extreme poverty.

PMID- 16650427
TI  - Quantitation of artemisinin and its biosynthetic precursors in Artemisia annua L.
      by high performance liquid chromatography-electrospray quadrupole time-of-flight
      tandem mass spectrometry.
AB  - This study reports the development and validation of a rapid, sensitive and
      selective assay for the quantitation of artemisinin, arteannuin B, artemisitene
      and artemisinic acid in Artemisia annua L. by reversed phase high performance
      liquid chromatography (HPLC) electrospray (ESI) quadrupole time of flight (Q-TOF)
      tandem mass spectrometry (MS/MS). A recovery of >97% for all analytes was
      achieved by immersing one gram of fresh plant material in chloroform for 1 min.
      This result supports the hypothesis that artemisinin and some of its structural
      analogs present in the leaves A. annua L. are localized entirely in the
      subcuticular space of the glands on the surface of the leaves. We validated the
      use of this chloroform extract, without additional sample preparation steps, for
      quantitative Q-TOF MS/MS. No ion suppression (matrix effect) resulting from
      interference with other compounds was detected. For every concentration within
      the range of the standard curve (0.1 to 3.00 microg/ml), accuracy was between 85%
      and 115%. Within- and between-day variations for the analysis of A. annua L.
      samples were <20%.

PMID- 16650428
TI  - Experimental design considerations in quantification experiments by using the
      internal standard technique: cholesterol determination by gas chromatography as a
      case study.
AB  - An overview on experimental design in quantification experiments using the
      internal standard technique is described. Particular emphasis is given to the
      modelling of the relationship analyte/internal standard and the estimation of the
      optimal amount of internal standard to be used throughout the analytical
      concentration range by using a uniform shell design with a minimum number of
      seven experiments. The described approach is demonstrated in the analysis of
      cholesterol in various reference materials by gas chromatography (GC), using
      alpha-5 cholestan as internal standard. The outlined approaches can be applied in
      the determination of any kind of analyte.

PMID- 16650429
TI  - Atrial repolarization as observable during the PQ interval.
AB  - OBJECTIVE: We aimed to study the involvement of atrial repolarization in body
      surface potentials. METHODS: Electrocardiograms of healthy subjects were recorded
      using a 64-lead system. The data analysis focused on the PQ intervals while
      devoting special attention to the low-amplitude signals during the PQ segment:
      the segment from the end of the P wave until onset QRS. The data were analyzed by
      inspecting body surface potential maps and the XYZ signals of the
      vectorcardiogram. RESULTS: Standard P-wave features exhibited normal values. The
      local potential extremes were found at positions not sampled by the standard
      leads. The PQ segment was found to be not isoelectric, the time course of the
      potential distribution being very similar to that during the P wave but for a
      reversed polarity and about 3-fold lower magnitudes. CONCLUSION: The results
      demonstrate a significant involvement of atrial repolarization during the PQ
      interval and essentially discordant "atrial T waves," suggesting a small
      dispersion of atrial action potential durations.

PMID- 16650430
TI  - Isolation of neutrophils from mouse liver: A novel method to study effector
      leukocytes during inflammation.
AB  - Neutrophils are phagocytic leukocytes that represent one of the first lines of
      defense during infection and injury. Neutrophils emigrate into tissues during
      inflammation and are phenotypically different compared to cells in the
      circulation. To further understand the biology of tissue-recruited neutrophils,
      we have developed a reliable method to isolate these cells from inflamed liver.
      Acute liver inflammation was induced in mice by systemic treatment with
      adenovirus vectors. Two hours following adenovirus treatment, livers were
      enzymatically digested and leukocytes isolated by Percoll density gradient
      centrifugation. Neutrophils were then purified by negative immunomagnetic
      separation. Neutrophils isolated in this manner were 95% pure as determined by
      flow cytometry and more than 97% viable by propidium iodide staining. In order to
      carry out molecular studies, we extracted high quality genomic DNA and RNA from
      isolated neutrophils. PCR was used to successfully amplify sample genes from
      isolated neutrophil DNA. Isolated neutrophil RNA was used in a ribonuclease
      protection assay to evaluate chemokine gene expression. Neutrophils were shown to
      express multiple chemokine mRNA transcripts including MIP-1 beta, MIP-2 and IP
      10. This work describes a novel method to isolate highly pure, viable neutrophils
      from pathologically inflamed tissue for subsequent detailed cellular and
      molecular analysis.

PMID- 16650431
TI  - New roles for key residues in helices H1 and H2 of the Escherichia coli H-NS N
      terminal domain: H-NS dimer stabilization and Hha binding.
AB  - Bacterial nucleoid-associated proteins H-NS and Hha modulate gene expression in
      response to environmental factors. The N-terminal domain of H-NS is involved in
      homomeric and heteromeric protein-protein interactions. Homomeric interaction
      leads to the formation of dimers and higher oligomers. Heteromeric interactions
      with Hha-like proteins modify the modulatory properties of H-NS. In this study,
      we have used NMR and mutagenesis of the N-terminal domain of H-NS to identify the
      Hha-binding region around helices H1 and H2 of H-NS. Two conserved arginine
      residues, R12 and R15, located in the same side and in adjacent turns of helix H2
      are shown to be involved in two different protein-protein interactions: R12 is
      essential for Hha binding and does not affect H-NS dimer formation, and R15 does
      not affect Hha binding but is essential for the proper folding of H-NS dimers.
      Our results demonstrate a close structural connection between Hha-H-NS
      interactions and H-NS dimerization that may be involved in a possible mechanism
      for the modulation of the H-NS regulatory activity by Hha.

PMID- 16650432
TI  - The safety implications of vehicle seat adjustments.
AB  - INTRODUCTION: The goal of this study was to gather information on the preferred
      front seat position of vehicle occupants and to determine the impact of variation
      in seat position on safety during crashes. METHOD: The study evaluated the
      relationship between seat position and occupant size using the chi-square test
      and compared the risk of severe injury for small females and large males with
      regard to forward and rearward seat position using logistic regression. RESULTS:
      While smaller drivers sat closer to the steering wheel than larger drivers, front
      passengers of all sizes used similar seat positions. Additionally, the risk of
      injury was higher for small, unbelted females in rearward seat positions and
      large males (belted and unbelted) in forward seat positions. CONCLUSIONS:
      Occupants who adjust their seats to positions that are not consistent with
      required federal tests are at a greater risk for severe injury in a crash.

PMID- 16650433
TI  - Isolation of mesenchymal stem cells from human vermiform appendix.
AB  - BACKGROUND: Recent findings have shown that pluripotent stem cells exist in areas
      outside the bone marrow (BM). Moreover, it has been demonstrated that the
      appendix is important for the development of mucosal gut immunity, and
      hematopoietic progenitors have been isolated from animal and human appendices.
      MATERIALS AND METHODS: Non-inflamed appendices removed during laparotomy were
      processed and cultured until the appearance of adherent cells. Differentiations
      (performed under osteogenic, adipogenic, and myogenic conditions) were confirmed
      by immunohistochemistry and cytochemistry. Polymerase chain reaction and
      cytofluorimetric analyses were performed to evidence the presence of genes and
      protein specific lineages in appendix-derived mesenchymal stem cells (ADMCs).
      RESULTS: ADMCs were present in non-inflamed appendices. ADMCs under osteogenic
      conditions differentiated in osteoblasts and showed increased alkaline
      phosphatase expression; at the gene level, we observed the expression of Core
      binding factor alpha 1 (Cbfa1) and osteocalcin in osteogenic induced ADMCs. Under
      adipogenic conditions, lipidic drops in the cytoplasm, expression of lipoprotein
      lipase (LpL), and peroxisome proliferator-activated receptor gamma were observed;
      under myogenic conditions, myotubes expressing muscle specific proteins like
      desmin were formed. Myogenic regulatory factor 4 and MyoD were selectively
      induced in the ADMCs under myogenic conditions. CONCLUSIONS: This study shows for
      the first time that mesenchymal stem cells can be isolated from normal appendices
      obtained from a pediatric and adult age group (0-18 years of age). This finding
      not only may further knowledge of the maturation of the intestinal immunesystem
      but also could indicate a new physiological role of the human vermiform appendix.

PMID- 16650434
TI  - National trends in the utilization of cholecystectomy in children.
AB  - BACKGROUND: Previous studies have suggested that indications for cholecystectomy
      in children have evolved over the past three decades contributing to an increased
      frequency of this procedure. The purpose of this study was to evaluate recent
      trends in utilization of cholecystectomy in children in the laparoscopic era.
      MATERIALS AND METHODS: Children (<15 year) undergoing cholecystectomy between
      1996 and 2003 were identified in the Nationwide Inpatient Sample. Underlying
      medical illness and related biliary tract conditions and procedures were
      identified using ICD-9 codes. Census data were used to calculate population-based
      rates stratifying by age and risk factors for cholelithiasis. Univariate and
      multivariate analyses were performed accounting for survey design. RESULTS:
      During the study period, an estimated 11,823 cholecystectomies were performed
      nationwide. While the population frequency of children with hemolytic anemia
      undergoing cholecystectomy did not significantly change, the frequency of
      children undergoing cholecystectomy without this risk factor increased from 1.5
      to 2.5 procedures/100,000 population (P = 0.03). The percentage undergoing
      cholecystectomy by a laparoscopic approach increased from 77 to 91% (P < 0.001),
      with the largest increase being observed in children <5 years old (36% versus
      90%, P < 0.001). While no significant differences in in-hospital surgical
      complications or mortality were observed, laparoscopic cholecystectomy was
      associated with a 2.3 d (P < 0.001) shorter length of stay than open
      cholecystectomy. CONCLUSIONS: The indications for cholecystectomy have continued
      to evolve in the laparoscopic era. While the increased use of laparoscopic
      cholecystectomy has been associated with decreased length of stay, this approach
      has not been associated with changes in in-hospital outcomes. The effect of these
      trends on rates of operative biliary tract injury and long-term outcome require
      additional study.

PMID- 16650435
TI  - Increased plasma fibrinogen predicts one-year mortality in patients with acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Increased plasma fibrinogen is a risk factor for vascular
      diseases related to atherosclerosis. Its long-term predictive value in stroke
      survivors is not established. We conducted this study to establish the
      significance of hyperfibrinogenemia as the possible predictor of 30-day and one
      year mortality in patients with acute ischemic stroke. METHODS: We studied 900
      unselected patients with ischemic stroke admitted to the hospital within 24 h
      after onset of symptoms. We noted demographic data, risk factors for stroke,
      neurological deficit and disturbances of consciousness on admission. We measured
      plasma concentration of fibrinogen and the body temperature on day 1 and
      registered vital status at 1, 3, 6 and 12 months after stroke. RESULTS: Mean
      concentration of plasma fibrinogen was 2.9 g/L and 25.2% of patients had
      increased plasma concentration of fibrinogen (i.e. > or = 3.5 g/L) on day 1.
      Patients with hyperfibrinogenemia were more likely to die after 1, 3, 6 and 12
      months than those with normal plasma fibrinogen (21.1% vs. 15.6%, 36.4% vs.
      24.6%, 42.6% vs. 27.3%, 45.7% vs. 31.2%, respectively; P < 0.001 for the last
      three differences). Hyperfibrinogenemia did not predict short-term case-fatality,
      but increased concentration of plasma fibrinogen was an independent predictor of
      one-year case-fatality (P = 0.013; OR: 1.69 (95% CI 1.12-2.55)). Other
      independent predictors of one-year case-fatality were: neurological deficit on
      admission, age, white blood cell count, and body temperature on day 1.
      CONCLUSIONS: Increased concentration of plasma fibrinogen shortly after ischemic
      stroke independently increases risk of death within one year after stroke.

PMID- 16650436
TI  - The relationship between MRI and PET changes and cognitive disturbances in MS.
AB  - Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50%
      of the patients. Only moderate correlations have been found between cognitive
      dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction
      in MS is probably related to the overall disease burden of the brain including
      abnormalities in normal appearing white matter (NAWM) and cortical grey matter,
      which is undetected with conventional magnetic resonance imaging (MRI). Hence,
      imaging techniques that embrace such abnormalities are needed to achieve better
      correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with
      multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of
      brain metabolism as the cortical cerebral metabolic rate of glucose are imaging
      methods that are able to provide information on axonal loss or dysfunction in
      both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA
      using multi-slice EPSI is a new promising method for measurement of the global
      neuron capacity and can be repeated with only little discomfort and without any
      risk for the patient.

PMID- 16650437
TI  - Comparative analysis of some models of gene regulation in mixed-substrate
      microbial growth.
AB  - Mixed-substrate microbial growth is of fundamental interest in microbiology and
      bioengineering. Several mathematical models have been developed to account for
      the genetic regulation of such systems, especially those resulting in diauxic
      growth. In this work, we compare the dynamics of three such models (Narang,
      1998a. The dynamical analogy between microbial growth on mixtures of substrates
      and population growth of competing species. Biotechnol. Bioeng. 59, 116-121;
      Thattai and Shraiman, 2003. Metabolic switching in the sugar phosphotransferase
      system of Escherichia coli. Biophys. J. 85(2), 744-754; Brandt et al., 2004.
      Modelling microbial adaptation to changing availability of substrates. Water Res.
      38, 1004-1013). We show that these models are dynamically similar--the initial
      motion of the inducible enzymes in all the models is described by the Lotka
      Volterra equations for competing species. In particular, the prediction of
      diauxic growth corresponds to "extinction" of one of the enzymes during the first
      few hours of growth. The dynamic similarity occurs because in all the models, the
      inducible enzymes possess properties characteristic of competing species: they
      are required for their own synthesis, and they inhibit each other. Despite this
      dynamic similarity, the models vary with respect to the range of dynamics
      captured. The Brandt et al. model always predicts the diauxic growth pattern,
      whereas the remaining two models exhibit both diauxic and non-diauxic growth
      patterns. The models also differ with respect to the mechanisms that generate the
      mutual inhibition between the enzymes. In the Narang model, mutual inhibition
      occurs because the enzymes for each substrate enhance the dilution of the enzymes
      for the other substrate. The Brandt et al. model superimposes upon this dilution
      effect an additional mechanism of mutual inhibition. In the Thattai and Shraiman
      model, the mutual inhibition is entirely due to competition for the phosphoryl
      groups. For quantitative agreement with the data, all models must be modified to
      account for specific mechanisms of mutual inhibition, such as inducer exclusion.

PMID- 16650438
TI  - Incorporating energy metabolism into a growth model of multicellular tumor
      spheroids.
AB  - Diffusion limitations in tumors create regions that are deficient in essential
      nutrients and contain a large number of quiescent and dying cells.
      Chemotherapeutic compounds are not effective against quiescent cells and
      therefore have reduced efficacy against tumors with extensive quiescence. We have
      formulated a mathematical model that predicts the extent and location of
      quiescence in multicellular spheroids. Multicellular spheroids are in vitro
      models of in vivo tumor growth that have proven to be useful experimental systems
      for studying radiation therapy, drug penetration, and novel chemotherapeutic
      strategies. Our model incorporates a realistic description of primary energy
      metabolism within reaction-diffusion equations to predict local glucose, oxygen,
      and lactate concentrations and an overall spheroid growth rate. The model
      development is based on the assumption that local cellular growth and death rates
      are determined by local ATP production generated by intracellular energy
      metabolism. Dynamic simulation and parametric sensitivity studies are used to
      evaluate model behavior, including the spatial distribution of proliferating,
      quiescent, and dead cells for different cellular characteristics. Using this
      model we have determined the critical cell survival parameters that have the
      greatest impact on overall spheroid physiology, and we have found that oxygen
      transport has a greater effect than glucose transport on the distribution of
      quiescent cells. By predicting the extent of quiescence based on individual
      cellular characteristic alone this model has the potential to predict therapeutic
      efficiency and can be used to design effective chemotherapeutic strategies.

PMID- 16650439
TI  - Evolution on distributive lattices.
AB  - We consider the directed evolution of a population after an intervention that has
      significantly altered the underlying fitness landscape. We model the space of
      genotypes as a distributive lattice; the fitness landscape is a real-valued
      function on that lattice. The risk of escape from intervention, i.e., the
      probability that the population develops an escape mutant before extinction, is
      encoded in the risk polynomial. Tools from algebraic combinatorics are applied to
      compute the risk polynomial in terms of the fitness landscape. In an application
      to the development of drug resistance in HIV, we study the risk of viral escape
      from treatment with the protease inhibitors ritonavir and indinavir.

PMID- 16650440
TI  - Invariants of DNA sequences based on 2DD-curves.
AB  - The leading eigenvalue of the matrix associated with a DNA sequence as a
      important invariant is effectively used in analysis of DNA sequences. Here, we
      propose a new invariant base on the 2DD-Curves of DNA sequences which is simple
      for calculation. We can use it as an alternative invariant to characterize the
      DNA sequence. The utility of the new parameter is illustrated on the DNA
      sequences of 11 species.

PMID- 16650441
TI  - Probing the effects of the well-mixed assumption on viral infection dynamics.
AB  - Viral kinetics have been extensively studied in the past through the use of
      spatially well-mixed ordinary differential equations describing the time
      evolution of the diseased state. However, emerging spatial structures such as
      localized populations of dead cells might adversely affect the spread of
      infection, similar to the manner in which a counter-fire can stop a forest fire
      from spreading. In a previous publication [Beauchemin, C., Samuel, J., Tuszynski,
      J., 2005. A simple cellular automaton model for influenza A viral infections. J.
      Theor. Biol. 232(2), 223-234], a simple two-dimensional cellular automaton model
      was introduced and shown to be accurate enough to model an uncomplicated
      infection with influenza A. Here, this model is used to investigate the effects
      of relaxing the well-mixed assumption. Particularly, the effects of the initial
      distribution of infected cells, the regeneration rule for dead epithelial cells,
      and the proliferation rule for immune cells are explored and shown to have an
      important impact on the development and outcome of the viral infection in our
      model.

PMID- 16650442
TI  - Oral-tolerance induction in diet-induced obese mice.
AB  - OBJECTIVE: It is known that immune functions are altered in various ways by
      obesity. However, changes in the intestinal immune system resulting from obesity
      remain poorly understood. Oral tolerance is a system that suppresses antigen
      specific immune responses to orally administrated antigens. The intestinal immune
      system is intimately associated with the oral tolerance system, that acts to
      prevent allergic and inflammatory diseases. In this study we investigated the
      effect of obesity on induction of oral tolerance to ovalbumin (OVA) in an animal
      model of obesity. RESEARCH METHODS AND PROCEDURES: Obese mice induced by a high
      fat diet and control mice were allowed free access for 3 days to a 1%-ovalbumin
      (OVA) solution in drinking water. After continuous feeding of the antigen, all
      the mice were immunized by two intraperitoneal injections of OVA administered 7
      days apart. RESULTS: In the control mice, induction of oral tolerance caused an
      increase in antigen specific IgG1 levels and a decrease in IgG2a levels. In
      contrast, the IgG1/IgG2a ratio was reversed in obese mice. OVA-specific IL-2
      production was suppressed by antigen feeding in both the control and obese mice;
      however, suppression of OVA-specific IL-10 was observed only in the control mice.
      Although OVA-specific IgA and IgM were not affected by antigen feeding, the obese
      groups of mice had significantly lower titers of antibodies. DISCUSSION: These
      findings suggest that obesity may affect induction of oral tolerance following
      antigen feeding and that these changes may be related to the inflammatory
      reaction.

PMID- 16650443
TI  - Dynamics of progestogenic activity in serum following administration of
      Ligusticum chuanxiong.
AB  - Many women are using botanical alternatives for menopausal hormone replacement
      therapy (HRT) because current progestins, compounds with progesterone activity,
      have adverse risk profiles. However the development of phyto-progestins for HRT
      is hampered by the absence of basic pharmacokinetic/pharmacodynamic (PK/PD) data
      due to the lack of methods to capture summated effects of the numerous compounds
      that contribute to bioactivity in vivo. In this study, we explored the utility of
      progesterone receptor (PR)-driven bioassays to track changes in serum
      progestogenic activity following administration of traditional Chinese medicinal
      herb, Ligusticum chuanxiong, with potent progestogenic activity. Sensitive and
      specific (>300-fold) increases in progestogenic activity were observed when HeLa
      cells transfected with PR and a PR-driven promoter were exposed to the
      progestogenic drug, medroxy-progesterone acetate (MPA), suggesting the utility of
      the bioassay to measure progestogenic effects for PK/PD studies. Progestogens
      were administered to male Sprague-Dawley rats and serum extracted for measurement
      of progestogenic activity. Effect-time studies indicate that injection of MPA and
      L. chuanxiong extract raised area-under-curve of progestogenic activity in sera
      by 8.2-fold (p<0.001) and 4.5-fold (p<0.01) respectively, compared to sera from
      rats administered vehicle only. Administration of MPA and L. chuanxiong extract
      by the oral route resulted in a 5.4 (p<0.001) and 2.3-fold (p=0.07) increase
      respectively. Our data suggest that PR-responsive reporter gene bioassays can
      measure bioavailability of compounds, known and unknown, of complex botanicals
      for hormone replacement therapy. L. chuanxiong extracts exert progestogenic
      activity in vivo, and may have utility for progesterone-replacement therapy.

PMID- 16650444
TI  - Beach morphodynamics forcements in oiled shorelines: Coupled physical and
      chemical processes during and after fuel burial.
AB  - In November 2002, the sinking of the Prestige oil tanker off the Galician coast
      (N.W. Spain) caused the largest ecological catastrophe in the history of Spain,
      affecting the coast called the 'Costa da Morte' (Galicia, N.W. Spain). This work
      is focused on the study of the oil contamination of the intertidal area of two
      beaches located on this stretch of coast. The study of twenty cores extracted
      from both beaches has identified fuel embedded in the sedimentary column up to a
      depth of 2.38 m (this being the maximum depth of extraction). This, along with
      the presence of oil below the groundwater indicates the existence of a new factor
      which determines the burial of oil: the morphodynamic behaviour of the beach.
      Furthermore, this morphodynamic variation conditions the physical appearance of
      the buried oil. Four different types have been identified: tar-balls (cm),
      particles (mm), oil coatings on sediment grains and on emulsion, with
      distribution patterns conditioned by the degree of wave exposure. The analysis of
      the information obtained have permitted the development of a conceptual model of
      the burial and oil evolution in the sedimentary column in relation to wave
      exposure, and thus to the morphodynamic variability of the beach.

PMID- 16650445
TI  - Silent mutations in the gene encoding the p53 protein are preferentially located
      in conserved amino acid positions and splicing enhancers.
AB  - The last release of p53 somatic mutation database contains more than 20,000 of
      mutation among which 951 are silent (synonymous). This striking amount of silent
      mutations is much more than what would be expected if synonymous mutations were
      effectively neutral. The prevalent explanation to reconcile this vast amount of
      silent mutations with the neutral expectation is that they are just the
      subproduct of the hypermutability process that affect cancer cells. Some
      evidences have been presented in this direction, and the explanation has been
      taken as granted. Assuming that silent mutations are effectively neutral has
      major implication in the investigation of mutational processes that affect the
      gene encoding the p53 protein, since on the basis of this assumption they are
      considered the Null hypothesis, for instance for measuring and comparing among
      tissues the endogenous mutability. From this it follows that determining whether
      silent mutations in the p53 gene, and in all disease genes in general, are or not
      basically mutational noise, is of paramount importance. In this paper we
      readdress this topic by testing whether there is a relationship between the
      spatial distribution of silent mutations inside the p53 gene and functional
      significant features of the gene. For this purpose we divided the population of
      silent mutations in three groups: those that are found accompanied by other
      mutations (doublets and multiplest), those that were isolated as singlets, but
      the same mutation was also isolated as being part of a doublet (or multiplet) in
      another individual. And the last group is composed by those that were always
      found as singlets and never as being part of a doublet or a multiplet. This last
      group was expected to be enriched in functionally significant silent mutations.
      We found that all silent mutations, but particularly those of the last group, are
      preferentially located in conserved amino acid positions (i.e. functionally
      important amino acids) and also tend to be located inside suspected splicing
      enhancers. Noteworthy, this association remains even after eliminating the
      possible contribution of mutation hotspots. Besides, we present additional
      evidence in the direction that these putative splicing enhancers are real
      functional enhancers.

PMID- 16650447
TI  - Magnetic resonance imaging of acoustic streaming: absorption coefficient and
      acoustic field shape estimation.
AB  - In this study, magnetic resonance imaging (MRI) is used to visualize acoustic
      streaming in liquids. A single-shot spin echo sequence (HASTE) with a saturation
      band perpendicular to the acoustic beam permits the acquisition of an
      instantaneous image of the flow due to the application of ultrasound. An average
      acoustic streaming velocity can be estimated from the MR images, from which the
      ultrasonic absorption coefficient and the bulk viscosity of different glycerol
      water mixtures can be deduced. In the same way, this MRI method could be used to
      assess the acoustic field and time-average power of ultrasonic transducers in
      water (or other liquids with known physical properties), after calibration of a
      geometrical parameter that is dependent on the experimental setup.

PMID- 16650448
TI  - Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine.
AB  - We earlier reported that immunization of macaques with a reverse transcriptase
      deleted SHIV(KU2) (DeltartSHIV(KU2)) plasmid that contained HIV-1(HXB2) env and
      SIV gag-nef induced protection against AIDS caused by challenge virus SHIV89.6P
      with a heterologous env. We further deleted vif and integrase from
      DeltartSHIV(KU2) and substituted the 3'LTR with SV40 poly A sequences, creating
      Delta4SHIV(KU2) (M) and a parallel construct containing gag-nef of HIV-1(SF2),
      Delta4SHIV(KU2) (H). Six macaques received two intramuscular injections of the
      (M) DNA, and another six received three injections of the (H) DNA. Three of the
      latter group received two post-challenge boosts with (M) DNA vaccine. Seven virus
      control macaques were inoculated with SHIV89.6P. All twelve immunized macaques
      were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT
      assays. Virus control animals all developed progressive infection, whereas
      vaccinated macaques from both groups controlled virus replication, with plasma
      viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA
      vaccine was efficacious even though it encoded Env, Gag, and Nef that were
      genetically distinct from the proteins in the challenge virus. The DNA vaccine
      induced broad-based protection without using viral proteins to boost the
      immunity.

PMID- 16650449
TI  - Requirements for capsid-binding and an effector function in TRIMCyp-mediated
      restriction of HIV-1.
AB  - In owl monkeys, a retrotransposition event replaced the gene encoding the
      retroviral restriction factor TRIM5alpha with one encoding TRIMCyp, a fusion
      between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A.
      TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism
      dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid
      protein. Here, we show that infection by retroviruses other than HIV-1 can be
      restricted by TRIMCyp, providing an explanation for the evolutionary retention of
      the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1
      infection occurs before the earliest step of reverse transcription. TRIMCyp
      mediated restriction involves at least two functions: (1) capsid binding, which
      occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil
      and cyclophilin A domains, and (2) an effector function that depends upon the B
      box 2 domain.

PMID- 16650450
TI  - Almost complete colour constancy achieved with full-field adaptation.
AB  - A successive asymmetric colour-matching task was used to study the changes in
      colour appearance of simulated Munsell samples. Colour shifts were induced with
      two Planckian illuminants, standard illuminant A (u'=0.256, v'=0.524) and
      illuminant S (u'=0.174, v'=0.392). Measurements were conducted with a 20 degrees
      field and a 120 degrees field. Adaptation period varied from 1 to 30s with the
      smaller field and from 1 to 60s with the larger field. Colour shifts were
      specified in terms of a modified Brunswik ratio (BR). Higher values of BR were
      associated with longer adaptation periods but only when the larger background was
      used. Supplementary experiments showed that the changes in colour appearance were
      related to a slight shift in the perceived colour of the background. The timing
      of the colour shifts are modelled in terms of cone opponent responses. High
      values of BR correspond to almost complete von Kries adaptation in all three cone
      types.

PMID- 16650451
TI  - Contextual effects on fine orientation discrimination tasks.
AB  - We examined the influence of context on fine orientation discrimination
      performance using sinusoidal grating patterns. Discrimination performance was
      impaired in the presence of modulated surrounds of the same spatial frequency,
      orientation, and contrast as the center. When center and surround were out-of
      phase, separated by a gap of mean luminance, or very different in spatial
      frequency, performance remained at control levels. When center and surround were
      in-phase but mismatched in mean luminance, suppression was reduced or eliminated
      and performance was equivalent to luminance-mismatched control conditions. We
      speculate that lateral interactions in fine orientation discrimination tasks do
      not occur between objects that are perceptually distinct.

PMID- 16650452
TI  - Attentional control over either of the two competing percepts of ambiguous
      stimuli revealed by a two-parameter analysis: means do not make the difference.
AB  - We studied distributions of perceptual rivalry reversals, as defined by the two
      fitted parameters of the Gamma distribution. We did so for a variety of bi-stable
      stimuli and voluntary control exertion tasks. Subjects' distributions differed
      from one another for a particular stimulus and control task in a systematic way
      that reflects a constraint on the describing parameters. We found a variety of
      two-parameter effects, the most important one being that distributions of
      subjects differ from one another in the same systematic way across different
      stimuli and control tasks (i.e., a fast switcher remains fast across all
      conditions in a parameter-specified way). The cardinal component of subject
      dependent variation was not the conventionally used mean reversal rate, but a
      component that was oriented-for all stimuli and tasks-roughly perpendicular to
      the mean rate. For the Necker cube, we performed additional experiments employing
      specific variations in control exertion, suggesting that subjects have to a
      considerable extent independent control over the reversal rate of either of the
      two competing percepts.

PMID- 16650453
TI  - Contrast detection in noise with positive and negative defocus in myopes.
AB  - PURPOSE: Previous studies have shown that myopes produce an asymmetrical loss in
      contrast sensitivity with positive and negative defocusing lenses at low-medium
      spatial frequencies (1-7c/deg) compared to non-myopes. The measurement of
      contrast detection in noise allows any given loss in visual sensitivity to be
      attributed to two components namely sampling efficiency and/or equivalent noise.
      Previous work has also shown that sampling efficiency gives an indication of the
      neural effects and in the absence of sampling efficiency changes, changes in
      equivalent noise levels are considered to be due to optical factors. We
      investigate whether the asymmetrical loss shown by myopes to defocus can be
      explained by changes in sampling efficiency or equivalent noise, or both.
      METHODS: Contrast thresholds in four different levels of externally added noise
      were measured in five myopic and five non-myopic subjects for Gabors of 3c/deg.
      Measurements were obtained under cycloplegia with 0 D, +/-0.50 D, and +/-1.00 D
      defocusing lenses. RMS wavefront aberrations were also measured using a Shack
      Hartmann aberrometer. RESULTS: In the absence of noise, there was no significant
      difference in contrast sensitivity without defocus between myopes and emmetropes.
      When sampling efficiency and equivalent noise were measured from Contrast
      Detection in Noise functions, analysis of variance showed no significant
      difference in sampling efficiency between myopes and non-myopes (p=0.145). Myopes
      showed maximum levels of equivalent noise with +1.00 D defocus, decreasing to a
      minimum with -1.00 D defocus (p=0.009). Non-myopes showed a symmetrical increase
      in equivalent noise from zero for both positive and negative defocus. A
      significant correlation was found between equivalent noise and the total RMS of
      Wavefront aberrations of the eye (p=0.026). CONCLUSION: Optical factors explain
      the observed differences in contrast sensitivity with positive and negative
      defocus between myopes and non-myopes.

PMID- 16650454
TI  - The visual pigments of the West Indian manatee (Trichechus manatus).
AB  - Manatees are unique among the fully aquatic marine mammals in that they are
      herbivorous creatures, with hunting strategies restricted to grazing on sea
      grasses. Since the other groups of (carnivorous) marine mammals have been found
      to possess various visual system adaptations to their unique visual environments,
      it was of interest to investigate the visual capability of the manatee. Previous
      work, both behavioral (Griebel & Schmid, 1996), and ultrastructural (Cohen,
      Tucker, & Odell, 1982; unpublished work cited by Griebel & Peichl, 2003), has
      suggested that manatees have the dichromatic color vision typical of diurnal
      mammals. This study uses molecular techniques to investigate the cone visual
      pigments of the manatee. The aim was to clone and sequence cone opsins from the
      retina, and, if possible, express and reconstitute functional visual pigments to
      perform spectral analysis. Both LWS and SWS cone opsins were cloned and sequenced
      from manatee retinae, which, upon expression and spectral analysis, had
      lambda(max) values of 555 and 410 nm, respectively. The expression of both the
      LWS and SWS cone opsin in the manatee retina is unique as both pinnipeds and
      cetaceans only express a cone LWS opsin.

PMID- 16650455
TI  - Effect of a magnetic water treatment on homogeneous and heterogeneous
      precipitation of calcium carbonate.
AB  - In this paper are reported experimental results on the effect of a magnetic field
      on the precipitation process of calcium carbonate scale from a hard water.
      Carbonically pure water was circulated at a constant flow rate in a magnetic
      field. After this treatment, calcium carbonate precipitation was induced by
      degassing dissolved carbonic gas. The nucleation time was identified from the
      variations of the pH and the Ca(2+) concentration. The ratio between homogeneous
      and heterogeneous nucleation was determined from the measurement of the mass of
      precipitated calcium carbonate. It is shown that the magnetic treatment increases
      the total amount of precipitate. This effect depends on the solution pH, the flow
      rate and the duration of the treatment. In addition, the magnetic treatment
      modifies the ratio between homogeneous/heterogeneous nucleation. Homogeneous
      nucleation is promoted by an increasing the pH of water, the flow rate as well as
      the residence time. The magnetic treatment enhances these effects with a maximum
      for a 15 min treatment time. It is shown that the presence of calcium carbonate
      colloid particles is not necessary. It is advanced that the main magnetic effects
      concern the associations of ionic species which are present in the solution and
      which are involved in the nucleation process of calcium carbonate precipitation.

PMID- 16650456
TI  - UV spectra analysis for water quality monitoring in a fuel park wastewater
      treatment plant.
AB  - In the context of the high application potentials for on-line measurements in
      wastewater quality monitoring, UV spectroscopy has received recent attention. In
      the present work UV spectrophotometric analyses were coupled to principal
      component analysis (PCA) and cluster analysis (CA) to characterize samples taken
      from a fuel park wastewater treatment plant and to attempt preliminary
      contaminant identification in the treated wastewater. The score plot resulting
      from PCA identified two different groups of spectra, one including the influents
      to the biological reactor and the other the treated wastewater samples. Among the
      latter, weekday and weekend samples could be further distinguished. The same
      groups of samples were identified in a dendrogram from CA. The score plot and the
      dendrogram also allowed the tentative identification of employed process
      chemicals (lubricant and detergents) as residual contaminants in the treated
      effluent.

PMID- 16650457
TI  - Short-term interactions of aniline and benzidine with three soils in both natural
      and artificial matrices.
AB  - The fate of aromatic amines in natural systems is important to understand due to
      the persistence and toxicity of these chemicals. Laboratory experiments were
      performed to elucidate aniline and benzidine behavior in silty-clay, sandy loam,
      and sandy soils, and six background matrices (rainwater, 12.5 mM CaCl(2), 25 mM
      CaCl(2), and each passed through soil columns). The goals of this study were to
      test the validity of using CaCl(2) as a laboratory simulation for rainwater and
      to observe how short-term sorption (24 h) of aniline and benzidine changed when
      these solutions were passed through soil columns. Results indicated that neither
      CaCl(2) solution exactly predicted the sorption of these chemicals in
      corresponding rainwater solutions, likely due to varying soil properties that
      influenced the sorption mechanisms. Statistical analyses revealed that the
      passage of rainwater or CaCl(2) solutions through soil columns did not
      significantly affect the sorption of aniline or benzidine. Cation exchange and
      solubility plots were created to identify the sorption mechanisms taking place in
      the short-term batch experiments. These plots indicated that cation exchange
      played a role in the sorption of both aniline and benzidine under all conditions,
      while solubility plots showed higher correlations for benzidine, a consequence of
      its lower aqueous solubility.

PMID- 16650458
TI  - Evaluation of geochemical methods for discrimination of metal contamination in
      Antarctic marine sediments: a case study from Casey Station.
AB  - Detecting anthropogenic metal contamination in regional surveys can be
      particularly difficult when there is a lack of pre-disturbance data, especially
      when trying to differentiate low to moderate levels of contamination from
      background values. Furthermore, comparisons with other regional studies are
      confounded by differing analytical methods used and variations in sediment
      properties such as grainsize. Several types of geochemical technique, including
      weak acid partial extraction, strong acid extractions and total digestion have
      been used. Attempts have been made to overcome the influence that grainsize has
      on chemical concentrations in heterogeneous environments by analysing the fines,
      typically the mud fraction (<63 microm), in an attempt to improve the detection
      of anthropogenic contamination. Here we compare a weak acid partial extraction
      using 1M HCl and total digestion methods for a regional survey of reference and
      impacted sites in Antarctica using both whole sediment (<2 mm) and mud (<63
      microm) fractions. The 1M partial extraction on whole sediment (<2 mm) most
      closely distinguished weakly, or moderately, impacted sites from reference
      locations. It also identified small scale within-location spatial variation in
      metal contamination that the total digest did not detect. Compared with total
      digests or analysis of the <63 microm fraction alone, this method minimised the
      possibility of a Type II statistical error in the regional survey - that is,
      failing to identify a site as being contaminated when it has elevated metal
      concentrations. To allow inter-regional comparison of sediment chemistry data
      from elsewhere in Antarctica, and also more generally, we recommend a 1M HCl
      partial extraction on whole sediment (<2 mm).

PMID- 16650459
TI  - Zinc accumulation in Solanum nigrum is enhanced by different arbuscular
      mycorrhizal fungi.
AB  - Solanum nigrum was found to proliferate in sediments with high levels of metal
      pollution. The effect of Zn on plant growth and tissue metal accumulation was
      assessed. The response of the plant to the inoculation with four different
      isolates of arbuscular mycorrhizal fungi (AMF) (Glomus sp. BEG140, Glomus
      claroideum, Glomus mosseae and Glomus intraradices) was studied. While the
      isolates of AMF did not have a significant (P<0.05) influence on mycorrhizal
      colonisation, increasing Zn concentration to high levels (500 and 1000 mgkg(-1))
      induced significant (P<0.05) decrease of the AMF colonisation. In general, the
      presence of AMF did not affect the growth and biomass of S. nigrum individuals.
      However, the level of metal in the matrix affected S. nigrum growth; plants grown
      at 100 mgkg(-1) had significantly (P<0.05) lower leaf, stem, root and total
      biomass than control ones and plants growing at 500 and 1000 mgkg(-1) had the
      significantly (P<0.05) lowest biomass. Plants inoculated with the AMF G.
      claroideum and G. intraradices presented significantly (P<0.05) higher Zn
      accumulation in all plant tissues. In general, the stem tissues had the higher Zn
      content while the leaves registered the lowest values, which indicate a high
      translocation of the metal. AMF inoculation had no significant (P<0.05) influence
      on the metal translocation within the plant. This study suggests that inoculation
      with the AMF G. claroideum or G. intraradices, can enhance the Zn accumulation in
      the tissues of S. nigrum, not affecting the plant translocation capacities.

PMID- 16650460
TI  - Aggrecan expression is substantially and abnormally upregulated in Hutchinson
      Gilford Progeria Syndrome dermal fibroblasts.
AB  - Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder that
      displays features of segmental aging. It is manifested predominantly in
      connective tissue, with most prominent histological changes occurring in the
      skin, cartilage, bone and cardiovascular tissues. Detailed quantitative real time
      reverse-transcription polymerase chain reaction studies confirmed the previous
      observation that platelet-derived growth factor A-chain transcripts are
      consistently elevated 11+/-2- to 13+/-2-fold in two HGPS dermal fibroblast lines
      compared with age-matched controls. Furthermore, we identified two additional
      genes with substantially altered transcript levels. Nucleotide pyrophosphatase
      transcription was virtually shut down with decreased expression of 13+/-3- to
      59+/-3-fold in HGPS, whereas aggrecan mRNA was elevated to 24+/-5 times to 41+/-4
      times that of chronologically age-matched controls. Aggrecan, normally a
      component of cartilage and not always detectable in normal fibroblasts cultures,
      was secreted by HGPS fibroblast lines and was produced as a proteoglycan. This
      demonstrates that elevated aggrecan expression and its secretion are aberrant
      features of HGPS. We conclude that HGPS cells can display massively altered
      transcript levels leading to the secretion of inappropriate protein species.

PMID- 16650461
TI  - Long-term personal exposure to traffic-related air pollution among school
      children, a validation study.
AB  - Several recent studies suggest an association between long-term exposure to
      traffic-related air pollution and health. Most studies use indicators of exposure
      such as outdoor air pollution or traffic density on the street of residence.
      Little information is available about the validity of these measurements as an
      estimate of long-term personal exposure to traffic-related air pollution. In this
      pilot study, we assessed outdoor and personal exposure to traffic-related air
      pollution in children living in homes on streets with different degree of traffic
      intensity. The personal exposure of 14 children aged 9-12 years to 'soot', NO(x)
      (NO and NO(2)) was assessed in Amsterdam between March and June 2003. Each
      child's personal exposure was monitored during four repeated 48-h periods.
      Concurrently, in- and outdoor NO(x) measurements were carried out at the school
      and at the home of each participating child. Measurements were supplemented by a
      questionnaire on time activity patterns and possible indoor sources. Flow
      controlled battery operated pumps in a made-to-fit backpack were used to sample
      personal exposure to 'soot', determined from the reflectance of PM(2.5) filters.
      Exposure to NO(x) was assessed using Ogawa passive samplers. Children living near
      busy roads were found to have a 35% higher personal exposure to 'soot' than
      children living at an urban background location, despite that all children
      attended the same school that was located away from busy roads. Smaller contrasts
      in personal exposure were found for NO (14%), NO(2) (15%) and NO(x) (14%). This
      finding supports the use of 'living near a busy road' as a measure of exposure in
      epidemiological studies on the effects of traffic-related air pollution in
      children.

PMID- 16650462
TI  - Distribution of polychlorinated biphenyls, organochlorine pesticides and
      polybrominated diphenyl ethers in human umbilical cord serum, maternal serum and
      milk from Wielkopolska region, Poland.
AB  - The levels of organochlorinated pesticides (OCPs): p,p'-DDT and its metabolites,
      hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes and
      their metabolites, and 18 polychlorinated biphenyl (PCB) congeners were measured
      in maternal serum, umbilical cord serum and human milk collected from 22 mothers
      living in the Wielkopolska region, Poland. Additionally, 11 polybrominated
      diphenyl ether (PBDE) congeners were measured in the human milk samples. p,p'-DDT
      and its major metabolite, p,p'-DDE, together with HCB, were found in all milk and
      serum samples. Median concentrations of p,p'-DDE in maternal serum, umbilical
      cord serum and milk were 343, 329 and 634ng/g lipid weight (lw). PCB congeners
      138, 153 and 180 were the major congeners measured in all serum samples, while CB
      170 was detected in 74% and 100% of umbilical cord and maternal serum,
      respectively. Except for CBs 74, 101 and 105, which had a detection frequency of
      77%, 23% and 82%, respectively, all investigated PCB congeners were measured in
      all human milk samples. The median concentrations of sum PCBs in maternal serum,
      umbilical cord serum and milk were 79, 60 and 133 ng/g lw, respectively. A good
      correlation (Spearman R(S)>0.75, p<0.001) was found for major PCBs, p,p'-DDT and
      p,p'-DDE, between maternal and umbilical cord serum, while the correlation was
      weaker between milk and serum. The median of sum PBDEs in human milk was 2.0 ng/g
      lw (range 0.8 to 8.4), with BDE 47 being always the most abundant PBDE congener
      and, together with BDE 153, being present in all samples. In general, results
      found in the investigated group are at the low end of the concentration range
      measured in Europe.

PMID- 16650463
TI  - Hydrogen sulfide (H2S) and sour gas effects on the eye. A historical perspective.
AB  - The toxicology of hydrogen sulfide (H(2)S) and sour gas on the eye has a long
      history beginning at least with Ramazzini's observations [Ramazzini B. Diseases
      of Workers--De Morbis Artificum Diatriba--1713. Wright WC (trans). New York, C.
      Hafner Publishing Co Inc.; 1964. 98-99 pp.]. In contrast, a recent review by
      Alberta Health and Wellness (AHW Report) concluded that there is little evidence
      of eye irritation following short-term exposures to H(2)S at concentrations up to
      100ppm and that the H(2)S literature on the eye is a series of unsubstantiated
      claims reproduced in review articles dating back to the 1930s [Alberta Health and
      Wellness (AHW report). Health effects associated with short-term exposure to low
      levels of hydrogen sulfide: a technical review, Alberta Health and Wellness,
      October 2002, 81pp.]. In this paper, we evaluated this claim through a historical
      review of the toxicology of the eye. Ramazzini noted the effects of sewer gas on
      the eye [Ramazzini B. Diseases of Workers--De Morbis Artificum Diatriba--1713.
      Wright WC (trans). New York, C. Hafner Publishing Co Inc. 1964. 98-99 pp.].
      Lehmann experimentally showed eye effects in men at 70-90ppm H(2)S and also in
      animals [Lehmann K. Experimentalle Studien uber den Einfluss technisch und
      hygienisch wichtiger Gase und Dampfe auf den Organismus. Arch Hyg 1892;14:135
      189]. In 1923, Sayers, Mitchell and Yant reported eye effects in animals and men
      at 50ppm H(2)S. Barthelemy showed eye effects in animals and men at 20ppm H(2)S
      [Barthelemy HL. Ten years' experience with industrial hygiene in connection with
      the manufacture of viscose rayon. J Ind Hyg Toxicol 1939;21:141-51]. Masure
      experimentally showed that H(2)S is the causative agent of eye impacts in animals
      and men [Masure R. La Keratoconjunctivite des filatures de viscose; etude
      clinique and experiementale. Rev Belge Pathol 1950;20:297-341]. Michal upon
      microscopic examination of the rat's cornea, found nuclear pyknosis, edema and
      separation of cells in the eye following exposures for 3h at 36ppm H(2)S [Michal
      FV. Eye lesions caused by hydrogen sulfide. Cesk Ophthalmol 1950;6;5-8]. In 1975,
      in Alberta, irreversible eye damage and photophobia were experimentally produced
      in calves exposed to 20ppm H(2)S for 1week [Nordstrom GA. A study of calf
      response of ammonia and hydrogen sulfide gases. Thesis, University of Alberta,
      Department of Agricultural Engineering, Edmonton Alberta; 1975, 218 pp.]. Alberta
      Environmental Centre documented clinical irritation of the eye at 40ppm H(2)S in
      6 hours in rats [Alberta Environmental Centre. Morphological observations in rats
      exposed for six hours to an atmosphere of 0, 56, or 420mg/m(3) hydrogen sulfide.
      AECV86-A1. Alberta Environmental Centre, Vegreville, Alberta; 1986b. 28 pp.]. In
      two sour gas blow-outs in Alberta, in the early 1980s, eye injury was documented
      in humans and animals at 0.5 ppm H(2)S. Community studies in the United States,
      Europe and New Zealand suggest that acute exposure to 25ppb H(2)S is the lowest
      concentration to irritate the eyes; with chronic exposure, serious eye effects
      are suggested. In contrast to the conclusion, all of the studies, except one,
      cited in the AHW Report indicate toxic effects on the eye below 100ppm H(2)S
      [Alberta Health and Wellness (AHW report). Health effects associated with short
      term exposure to low levels of hydrogen sulfide (H(2)S): a technical review,
      Alberta Health and Wellness, October 2002, 81pp.]. In addition, the AHW Report
      (2002) mis-presented two studies as 'clinical studies', claiming they reported no
      evidence of eye effects in humans from 2 and 30 ppm H(2)S for 30-40 minutes
      [Alberta Health and Wellness (AHW report). Health effects associated with short
      term exposure to low levels of hydrogen sulfide (H(2)S): a technical review,
      Alberta Health and Wellness, October 2002, 81pp.].

PMID- 16650464
TI  - Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of
      human endometrial cancer.
AB  - OBJECTIVE: The high temperature requirement factor A (HTRA) family consists of
      serine proteases with domains homologous to those of bacterial HTRA. Four human
      HTRA members have been described: HTRA1-4. HTRA1 and HTRA3 share a high degree of
      domain homologies and may therefore share a functional similarity. HTRA1 mRNA and
      protein is reported to be down-regulated in SV40-transformed cells, a malignant
      melanoma cell line, ovarian tumors, and ovarian cancer cell lines, suggesting a
      progressive loss of HTRA1 and the protein in cancer. This raises the possibility
      that HTRA3 may likewise be involved in cancer. This study examined the expression
      of mRNA and protein levels of HTRA1 and HTRA3 in human endometrial cancer (EC).
      METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was
      performed in normal endometrium (n = 4) and in three grades of EC (n = 5 for each
      EC grade). Immunohistochemistry was used to determine the protein expression and
      the cellular localization of HTRA1 and HTRA3 in normal endometrium tissue (n = 6)
      and in three grades of EC (n = 8-10 for each EC grade). RESULTS: RT-PCR analysis
      showed a significant reduction of HTRA1 and HTRA3 mRNA in endometrial cancer
      compared to normal endometrium. HTRA1 and HTRA3 protein showed a similar pattern
      of expression in EC tissue. Positive immunostaining, scored semiquantitatively,
      revealed a significant decrease of HTRA1 and 3 protein expression with increasing
      grades of EC. CONCLUSION: These data suggest that HTRA1 and HTRA3 mRNA and
      protein levels decrease with increasing grades of EC.

PMID- 16650465
TI  - Gonadal steroid regulation of mood: the lessons of premenstrual syndrome.
AB  - New models for menstrual cycle-related mood disorders provide unique
      opportunities to gain insight into the processing of emotional information and
      the regulation of mood state by reproductive steroids. This paper reviews the
      role of reproductive steroids in affect regulation and in premenstrual dysphoric
      disorder (PMD), parses PMD into component processes that suggest potential
      mediating neurocircuitry, and highlights the importance of and potential
      contributors to the differential sensitivity that permits reproductive steroids
      to destabilize mood in some but not all women.

PMID- 16650466
TI  - Strain-dependent sex differences in the effects of alcohol on cocaine-induced
      taste aversions.
AB  - Research using the conditioned taste aversion procedure has reported that a
      cocaine/alcohol combination induces a significantly stronger taste aversion than
      either cocaine or alcohol alone. These findings suggest that the co
      administration of alcohol intensifies the aversive effects of cocaine. Although
      the behavioral interaction of cocaine and alcohol is well established, little is
      known about how the effects of this drug combination might be modulated by a
      variety of subject variables. The current investigation addressed this by
      assessing if the ability of alcohol to potentiate cocaine-induced taste aversions
      is dependent upon the strain and/or sex of the subject. In this series of
      studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley
      (Experiment 2) descent were given limited access to a novel saccharin solution to
      drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol
      (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every
      fourth day for a total of four conditioning trials. All subjects were then
      compared on an Aversion Test that followed the fourth conditioning cycle. In
      three of the groups tested (male Long-Evans; male and female Sprague-Dawley),
      cocaine induced a significant taste aversion that was unaffected by the co
      administration of alcohol. However, in female Long-Evans subjects, the addition
      of alcohol significantly strengthened the avoidance of the saccharin solution.
      Although the effects of alcohol on cocaine-induced taste aversions are dependent
      upon an interaction of sex and strain, the basis for this SexxStrain interaction
      is not known. That such an interaction is evident suggests that attention to such
      factors in assessing the effects of drug combinations is important to
      understanding the likelihood of the use and abuse of such drugs.

PMID- 16650467
TI  - Lanosterol 14alpha-demethylase expression in the mouse ovary and its
      participation in cumulus-enclosed oocyte spontaneous meiotic maturation in vitro.
AB  - The expression of lanosterol 14alpha-demethylase (LDM) in the mouse ovary after
      gonadotrophin administration was examined and the action of follicle fluid
      meiosis activating sterol (FF-MAS), derived from lanosterol by the action of LDM,
      on oocyte spontaneous maturation was also evaluated in cumulus cell enclosed
      oocytes (CEOs). Expression of LDM was primarily in oocytes in primordial and
      secondary follicles prior to administration of gonadotrophins, but obvious LDM
      expression was apparent in ovarian somatic cells 48 h after administration of
      equine chorionic gonadotrophin (eCG), especially in luteal and cumulus cells 54 h
      after eCG or 48 h after eCG plus 6 h after human chorionic gonadotrophin (hCG).
      The LDM expression in oocytes was only slightly elevated in larger growing
      follicles after eCG treatment. On the contrary, 48 h after hCG treatment, the
      elevated expression of LDM was only detected in interstitial cells. Therefore,
      eCG may be the primary gonadotrophin for LDM expression, and furthermore for
      production of FF-MAS in mouse cumulus cells (which are indispensable for oocyte
      maturation in vivo). Conversely, inhibitors of LDM, either 40 microM azalanstat
      or 50 microM RS-21745, significantly inhibited oocyte germinal vesicle breakdown
      (GVB) after 4h of in vitro culture; GVB rates decreased to 14 or 20%, compared to
      90% in spontaneous maturation, respectively. There was no significant increase in
      GVB in CEOs following specific inhibitor of sterol Delta14-reductase and Delta7
      reductase, AY9944-A-7 (5-100 microM), until marked oocytes degeneration appeared
      (50 microM). The phenomena may be ascribed to slow, passive accumulation of FF
      MAS by AY9944-A-7, which cannot be associated with fast spontaneous progression.
      Furthermore, in spontaneous-matured CEOs, LDM was expressed preferentially in
      cumulus cells instead of oocytes. Therefore, FF-MAS may have a positive role in
      the spontaneous maturation of CEOs. In conclusion, there was an eCG-dependent
      dual LDM expression pattern on both oocytes and somatic cells in growing
      follicles in vivo, which may increase LDM expression and FF-MAS production in
      cumulus cells for oocyte maturation. For the first time, the inhibitory effect of
      LDM inhibitors on spontaneous maturation, together with the strong LDM expression
      in spontaneous matured CEOs, indicated that FF-MAS produced by cumulus cells
      might participate in spontaneous maturation of mouse CEOs.

PMID- 16650468
TI  - Association between milk production and treatment response of ovarian cysts in
      lactating dairy cows using the Ovsynch protocol.
AB  - The objective of this study was to evaluate the association between the level of
      milk production on the day of diagnosis of ovarian cysts and treatment response
      using the Ovsynch protocol. On the day of cyst diagnosis (Day 0), 260 lactating
      dairy cows with ovarian cysts were treated with gonadotropin-releasing hormone
      (GnRH), PGF2alpha on Day 7, GnRH on Day 9, and timed inseminated 16-20 h later
      (Ovsynch protocol). Pregnancy was determined (by transrectal palpation) between
      42 and 49 days after insemination. On Day 0, data for milk production (kg/day),
      parity, days in milk (DIM), and body condition score (BCS) were recorded. Using
      the median value for milk production on the day of diagnosis, cows were
      classified as high producers (>28.5 kg) and low producers (<or=28.5 kg). Cows
      were classified as primiparous (first lactation) or multiparous (second or more
      lactations). Data for conception rate (CR) were analyzed using logistic
      regression accounting for milk production on the day of diagnosis, parity, DIM,
      and BCS. The CR for low and high producers was 6 and 16%, respectively. There was
      no association between DIM and BCS with the other variables (P>or=0.05).
      Primiparous cows were more likely (adjusted odds ratio: AOR=3.63; 95% CI: 95%
      confidence intervals=1.28-10.30; P<or=0.01) to become pregnant than multiparous
      cows, and low producers were less likely (AOR=0.31; 95% CI=0.11-0.85; P<or=0.02)
      to become pregnant than high producers. It was concluded that cows with high milk
      production on the day of cyst diagnosis were more likely to become pregnant
      following treatment than cows with low milk production. It appears paradoxical
      that high milk production predisposes to the occurrence of ovarian cysts, but
      that high-producing cows respond better to treatment compared to low-producing
      cows. It is hypothesized that the level of milk production on the day of cyst
      diagnosis could be an additional potential predictor of success to treatment of
      lactating cows with ovarian cysts using the Ovsynch protocol.

PMID- 16650469
TI  - Gonadotropin-releasing hormone (GnRH) and its natural analogues: a review.
AB  - The pivotal role of gonadotropin-releasing hormone (GnRH) during the hormonal
      regulation of reproductive processes is indisputable. Likewise, many factors are
      known to affect reproductive function by influencing either GnRH release from
      hypothalamus or pituitary gland responsiveness to GnRH. In veterinary medicine,
      GnRH and its agonists (GnRHa) are widely used to overcome reduced fertility by
      ovarian dysfunction, to induce ovulation, and to improve conception rate. GnRHa
      are, moreover, integrative part of other pro-fertility treatments, e.g. for
      synchronization of the estrous cycle or stimulation for embryo transfer.
      Additionally, continuous GnRH which shows desensitizing effects of the pituitary
      ovarian axis has been recommended for implementation in anti-fertility treatments
      like inhibition of ovulation or reversible blockade of the estrous cycle. Just as
      much, another group of GnRH analogues, antagonists, are now in principle
      disposable for use. For a few decades, GnRH was thought to be a unique structure
      with a primary role in regulation gonadotropins. However, it became apparent that
      other homologous ligands of the GnRH receptor (GnRHR) exist. In the meantime,
      more than 20 natural variants of the mammalian GnRH have been identified in
      different species which may compete for binding and/or have their own receptors.
      These GnRH forms (GnRHs) have apparently common and divergent functions. More
      studies on GnRHs should contribute to a better understanding of reproductive
      processes in mammals and interactions between reproduction and other
      physiological functions. Increased information on GnRHs might raise expectations
      in the application of these peptides in veterinary practice. It is the aim of
      this review to discuss latest results from evolutionarily based studies as well
      as first experimental tests and to answer the question how realistic might be the
      efforts to develop effective and animal friendly practical applications for
      endogenous GnRHs and synthetic analogues.

PMID- 16650470
TI  - The effect of continuous wavy micropatterns on silicone substrates on the
      alignment of skeletal muscle myoblasts and myotubes.
AB  - Tissue-engineered muscle is a viable option for tissue repair, though presently
      technologies are not developed enough to produce tissue in vitro identical to
      that in vivo. One important step in generating accurate engineered muscle is to
      mimic natural muscle architecture. Skeletal muscle is composed of fibrils whose
      organization defines functionality. In musculoskeletal myogenesis, aligning
      myoblasts in preparation for myotube formation is a crucial step. The ability to
      efficiently organize myoblasts to form aligned myotubes in vitro would greatly
      benefit efforts in muscle tissue engineering. This paper reports alignment of
      prefused and differentiated skeletal muscle cells in vitro by use of continuous
      micropatterned wavy silicone surfaces, with features sized 3, 6 and 12 microm in
      periodicity. Wave features with 6 microm periodicity produced the most healthy,
      aligned myoblasts. Alignment was found to be a function of plating density.
      Further growth on these substrates with aligned myoblasts promoted fusion,
      yielding healthy aligned myotubes. This method will be useful for applications in
      which differentiated myogenic cells need to be aligned unidirectionally as in the
      development of engineered muscle.

PMID- 16650471
TI  - Cultivation of garden vegetables in Peoria Pool sediments from the Illinois
      River: a case study in trace element accumulation and dietary exposures.
AB  - This case study was conducted to evaluate the use of reclaimed lake sediment as a
      growth media for vegetable production and to estimate whether accumulation of
      micronutrients and heavy metals in the vegetables would impact human nutrition or
      health, respectively. Five plant species, bean (Phaseolus vulgaris L.), broccoli
      (Brassica oleracea L.), carrot (Daucus carota L.), pepper (Capsicum annum L.),
      and tomato (Lycopersicon esculentum L.), were grown in pots containing either
      reclaimed sediment from the Illinois River or a reference soil. Edible and
      vegetative tissues from the plants were analyzed for 19 elements, including As,
      Cd, Cr, Cu, Hg, Mo, Ni, Pb, Se, and Zn. Tomato and pepper grown in sediment
      showed significantly greater biomass and yield as compared to plants from the
      reference soil. Elemental analysis of the tissues revealed that Zn and Mo were
      the only elements that were significantly greater in sediment-grown plants on a
      consistent basis. While significant, Zn concentrations were no more than 3-fold
      higher than those in plants from the reference soil. The same trend was observed
      for Mo, except for bean tissues, which showed a 10-fold greater concentration in
      sediment-grown plants. The projected dietary intake of Cu, Mo, and Zn from
      consumption of sediment-grown vegetable tissues was significantly higher than for
      soil-grown plants, although the contribution to the recommended dietary
      allowances (RDAs) for these elements was substantial only for Mo. Intake of
      sediment-grown beans would have provided 500% of the dietary Mo RDA. While this
      is below the lowest observable adverse effect level (LOAEL) value for this
      element, there is no evidence to indicate that there would be a nutritional or
      therapeutic benefit from the consumption of bean containing this level of Mo. The
      dietary exposures to Cd and Pb would have been below the pertinent limits for all
      age and gender groups with the exception of the cumulative dietary Cd exposure to
      the 1-3 year age group. The results from this study suggest that this reclaimed
      sediment can be utilized for the production of vegetables intended for human
      consumption. The results from this case study also suggest that sediment material
      with similar physicochemical characteristics and elemental concentrations that
      fall within the pertinent regulatory guidelines should also be a suitable and
      safe medium for vegetable production.

PMID- 16650472
TI  - Comparative gene expression of PSP-toxin producing and non-toxic Anabaena
      circinalis strains.
AB  - Blooms of the freshwater cyanobacterium Anabaena circinalis are recognised as an
      important health risk worldwide due to the production of a range of toxins such
      as saxitoxin (STX) and its derivatives, also known as paralytic shellfish
      poisoning (PSP) toxins. In this study the transcriptional profile of PSP toxin
      producing and non-toxic strains of A. circinalis was investigated by means of a
      DNA microarray approach. Additionally, gene expression was studied after exposure
      of toxic A. circinalis cultures to lidocaine hydrochloride at 1 microM for 2 h.
      Under standard growth conditions, a limited number of putative toxic-strain
      distinctive DNA fragments, identified in previous studies, were preferentially
      expressed in toxic versus non-toxic strains. The same genes did not significantly
      change their expression after exposure to 1 microM lidocaine, conditions
      previously shown to induce STX production in the cyanobacterium
      Cylindrospermopsis raciborskii T3. Lidocaine supplementation, however, enhanced
      the transcription of genes involved in physiological adaptive responses and bloom
      formation in cyanobacteria, such as the gas vesicle structural protein A and
      phycocyanin. The heat shock protein HSP-70 and the chlorophyll-a binding protein
      isiA were significantly repressed by lidocaine exposure. Stress response proteins
      and genes implicated in secondary metabolism were repressed, including
      phosphopantetheinyl transferases. The BGGM1 DNA microarray, used in this study,
      was shown to be suitable for gene expression studies in cultured toxic
      cyanobacteria and allowed the analysis of gene transcripts associated with
      surface scum formation by toxic A. circinalis.

PMID- 16650473
TI  - Alteration of steroidogenesis in H295R cells by organic sediment contaminants and
      relationships to other endocrine disrupting effects.
AB  - A novel bioassay with the human adrenocortical carcinoma cell line H295R can be
      used to screen for endocrine disrupting chemicals that affect the expression of
      genes important in steroidogenesis. This assay was employed to study the effects
      of organic contaminants associated with the freshwater pond sediments collected
      in the Ostrava-Karvina region, Czech Republic. The modulation of ten major genes
      involved in the synthesis of steroid hormones (CYP11A, CYP11B2, CYP17, CYP19,
      17betaHSD1, 17betaHSD4, CYP21, 3betaHSD2, HMGR, StAR) after exposure of H295R
      cells to sediment extracts was investigated using quantitative real-time
      polymerase chain reaction (PCR). Crude sediment extracts, containing high
      concentrations of polycyclic aromatic hydrocarbons (PAHs) and moderate amounts of
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)
      significantly stimulated expression of the CYP11B2 gene (up to 10-fold
      induction), and suppressed expression of 3betaHSD2 and CYP21 genes. A similar
      pattern was observed with the extracts after treatment with concentrated sulfuric
      acid to remove labile chemicals (including PAHs) leaving only persistent PCBs,
      OCPs and potentially PCDD/Fs. Comparison of the results with other
      mechanistically based bioassays (arylhydrocarbon receptor, AhR, mediated
      responses in H4IIE-luc cells, and estrogen receptor mediated effects in MVLN
      cells) revealed significant endocrine disrupting potencies of organic
      contaminants present in the sediments (most likely antiestrogenicity). Pronounced
      effects were observed particularly in sediment extracts from the Pilnok Pond
      which harbors an unusual intersexual population of the narrow-cawed crayfish
      Pontastacus leptodactylus (Decapoda, Crustacea). This pilot study provided the
      first experimental evidence of the wider application of the H295R bioassay for
      screening complex environmental samples, and the results support the hypothesis
      of chemical-induced endocrine disruption in intersexual crayfish.

PMID- 16650474
TI  - High-resolution retinal imaging of cone-rod dystrophy.
AB  - PURPOSE: This study examines a patient with cone-rod dystrophy using high
      resolution adaptive optics retinal imaging. Conventional ophthalmoscopes provide
      limited resolution due to their inability to overcome the eye's optical
      aberrations. In contrast, adaptive optics ophthalmoscopes correct these
      aberrations to provide noninvasive high-resolution views of the living retina. To
      date, adaptive optics ophthalmoscopy has been used mainly to examine the normal
      retina. Here we use adaptive optics ophthalmoscopy to image cone-rod dystrophy in
      vivo and compare these results with standard clinical tests. DESIGN:
      Observational case report. METHODS: High-resolution retinal images of a patient
      with cone-rod dystrophy were obtained with the University of Rochester adaptive
      optics flood-illuminated ophthalmoscope and the adaptive optics scanning laser
      ophthalmoscope located at the University of Houston and compared with standard
      clinical tests, including fundus photography, Goldmann visual fields, fluorescein
      angiography, optical coherence tomography, electroretinography, and multifocal
      electroretinography. MAIN OUTCOME MEASURES: Direct measurement of cone density
      and diameter and comparison of adaptive optics images with standard clinical
      imaging and functional tests. RESULTS: Adaptive optics images were acquired at
      multiple retinal locations throughout a clinically detected bull's-eye lesion.
      Within the atrophic regions, we observed large areas devoid of wave-guiding
      cones. In contrast, regions that appeared relatively spared by clinical
      examination contained a completely tiled cone mosaic. However, in these areas the
      cones were abnormally large, resulting in a 6.6-fold reduction from the normal
      peak cone density (patient peak density: 30 100 cones/mm2, normal peak density:
      199 200 cones/mm2). Multifocal electroretinography confirmed a 5.5-fold reduction
      in amplitude of the central peak (10.8 nanovolts/degree2 vs. 59.8
      nanovolts/degree2). CONCLUSIONS: Adaptive optics ophthalmoscopy is a noninvasive
      technique to observe a patient's retinal pathology directly at a cellular level.
      It can provide a quantitative measurement of photoreceptor loss in retinal
      disease.

PMID- 16650475
TI  - Small choroidal melanocytic lesions: features predictive of growth.
AB  - PURPOSE: To evaluate clinical features at presentation of small choroidal
      melanocytic lesions that were predictive of growth. DESIGN: Retrospective
      observational case series. PARTICIPANTS: A cohort of 240 patients with a
      presumptive diagnosis of small choroidal melanocytic lesions who were observed to
      document growth before treatment. METHODS: Data regarding size, location,
      diagnostic features, and growth were collected. To evaluate the diagnostic
      features at presentation, Barnard and Fisher exact tests were performed for
      categorical variables, and the Wilcoxon rank sum test was used for continuous
      factors. MAIN OUTCOME MEASURE: Documented growth. RESULTS: Eleven patients with
      small choroidal melanocytic lesions (4.6%) demonstrated growth within 50 months
      of follow-up. Lesions that demonstrated growth were significantly thicker (> or
      =2.0 mm; P<0.001) and closer to the foveola (<3.0 mm; P = 0.002). Significant
      increases in the risk of growth also were observed for gender (male), presence of
      symptoms, and orange pigment. CONCLUSIONS: Significant clinical features of small
      choroidal melanocytic lesions predictive of growth are greater thickness (> or
      =2.0 mm), location closer to the foveola (<3.0 mm), and presence of symptoms and
      orange pigment.

PMID- 16650476
TI  - The return of the dark neuron. A histological artifact complicating contemporary
      neurotoxicologic evaluation.
AB  - A common histological artifact of brain is the presence of contracted, intensely
      stained neurons. Such cells are termed dark neurons, and can be produced by post
      mortem manipulation or trauma in brain tissue. In a number of recently published
      experimental neurotoxicology reports cells of this nature are interpreted as
      representing dying or degenerating neurons, thus assigning inappropriate
      neurotoxic potential to the compounds administered. The latter are the commonly
      used drugs and pesticides DEET (N,N-diethyl m-toluamide), malathion, permethrin
      and pyridostigmine bromide. In this paper I review the nature and genesis of the
      dark neuron, critically discuss the neuropathologic validity of indicated studies
      and make a plea for increased awareness of this common artifact.

PMID- 16650477
TI  - Modelling calcium carbonate biomineralisation processes.
AB  - The structure-directing influence of the organic dicarboxylates malonate,
      succinate, glutarate and adipate as templating species on the hydrothermal
      formation of CaCO(3) was investigated at different temperatures (60, 80, 90, 120,
      150 and 190 degrees C) and with a range of molar ratios of [Ca(2+)]/[templating
      species] (20, 14.3, 10, 7.7, 5, 1, 0.5 and 0.33). In the presence of the
      dicarboxylates, one, two or three polymorphs of CaCO(3) - calcite, aragonite and
      vaterite - could be formed, depending on the reaction conditions. In addition
      changes in crystal morphology were observed for the CaCO(3) polymorphs depending
      on the concentration of the template. In contrast, synthesis under ambient
      conditions of temperature and pressure resulted only in calcite formation,
      although template-dependent morphological changes were again observed.
      Crystalline products were all characterized by powder X-ray patterns and SEM
      (Scanning Electron Microscopy) micrographs. The ambient reactions with the
      chelating, dinucleating carboxylato ligands H(3)heidi and H(5)hpdta produce more
      profound changes in calcite morphology. With H(3)heidi rounded calcite crystals
      with shapes similar to that of otoliths are formed and with H(5)hpdta the
      formation of microtrumpets of constructed from bundles of nanocrystals of calcite
      is observed. The possible mode of action of these ligands on calcite formation is
      discussed in the context of known coordination chemistry with other metal ions.

PMID- 16650478
TI  - A multidrug-resistant Pseudomonas aeruginosa isolate from a lethal case of sepsis
      induces necrosis of human neutrophils.
AB  - A multidrug-resistant Pseudomonas aeruginosa (r-Pa) was isolated from a lethal
      case of sepsis in a bone marrow transplant recipient. Genotypic analysis of P.
      aeruginosa isolates demonstrated that sepsis was secondary to gut colonization.
      The interactions between r-Pa and patient's neutrophils were studied. The results
      indicate that: (1) the patient's neutrophil killing activity and nitric oxide
      production against r-Pa or drug sensitive P. aeruginosa (s-Pa) were profoundly
      impaired; (2) r-Pa cells, but not s-Pa cells or their filtered culture
      supernatants, induced necrosis of healthy donor neutrophils. Neutrophil necrosis
      emerges as a remarkable event in the pathogenesis of P. aeruginosa sepsis.

PMID- 16650479
TI  - Determination of the amino acid sequence in a cyclic lipopeptide using MS with
      DHT mechanism.
AB  - A TOF MS/MS method to directly determine the amino acid sequence in a cyclic
      lipopeptide without its hydrolysis is described. The fragments of the peptide and
      the hydrocarbon chains were identified through comparing the MS of two analogues
      of the lipopeptide; the connecting relationship of amino acid residues in the
      lipopeptide was determined based on the difference of mass to charge ratio
      between peaks in the MS spectra and the amino acid analysis; and finally,
      according to the mechanism of double hydrogen transfer(DHT) the C-terminal of
      peptide and hydroxy aliphatic acid in the lipopeptide was directly determined
      without the hydrolysis. The determined sequence of amino acid residues in the
      cyclic lipopeptide is also supported by the rest peaks in the MS spectra grounded
      on simple fragmenting mechanism. This method can be used to determine the amino
      acid sequence in any aliphatic acid loop-inlaying cyclic lipopeptides.

PMID- 16650480
TI  - Investigation on drug dissolution and particle characteristics of pellets related
      to manufacturing process variables of high-shear granulation.
AB  - There is a growing interest for multiparticulate solid dosage forms such as
      pellets, because of their several advantages over tablets during drug therapy. It
      is essential to investigate the drug dissolution process which can be influenced
      by the composition and manufacturing process technology, too. This study was
      performed applying experimental design in order to evaluate the effects of
      independent process variables during high-shear pelletisation, taking the
      impeller speed (x1) and granulation binder flow rate (x2) as factors into
      consideration. Theophylline containing pellet formulation was prepared using a
      matrix consisted of ethylcellulose, microcrystalline cellulose and lactose.
      Dissolution profiles were modeled by the Weibull function to evaluate the power
      of process variables. Both process variables were powerful to influence the
      particle agglomeration. A linear regression was found between the particle size
      and the diffuse reflectance values after the Kubelka-Munk transformation.
      Differences in the diffuse reflectance spectra of pellet samples related to
      particle size offer a fast instrumental method for the in-process control.

PMID- 16650481
TI  - Typus melancholicus: personality structure and the characteristics of major
      unipolar depressive episode.
AB  - BACKGROUND: The melancholic type of personality (TM) has long been considered in
      continental and Japanese psychopathology as a relevant vulnerability trait
      constellation for the development of depression. METHOD: The symptom presentation
      in an outpatient population of 116 subjects suffering from a DSM-IV major
      depressive episode was rated according to the standardized documentation system
      of the Association for Methodology and Documentation in Psychiatry (AMDP).
      Personality features were explored by means of the Criteria for Typus
      Melancholicus (CTM). RESULTS: Statistically significant differences in depression
      related psychopathological scores (i.e. higher level of guilt feelings, feeling
      of the loss of feelings, loss of vital drive and lower degrees of irritability
      and dysphoria) were found between TM and non-TM subjects, supporting the
      phenomenic specificity of TM depression at both symptom and subsyndromal level.
      LIMITATION AND CONCLUSIONS: Although our results were obtained in a selected
      sample of outpatients at an University Mental Health Center, they are indicative
      of psychopathological differences between TM and NTM in the core symptoms of
      depression. These differences highlight the importance of including TM criteria
      for phenotypic characterization of depressive disorder, suggesting that it may
      improve diagnostic and therapeutic practice and might be a reasonable
      psychopathologic endophenotype in investigating affective-spectrum vulnerability
      in at-risk populations.

PMID- 16650482
TI  - Factor structure and internal consistency of the Young Schema Questionnaire
      (Short Form) in Korean and Australian samples.
AB  - We investigated cross-cultural differences in the factor structure and
      psychometric properties of the 75-item Young Schema Questionnaire-Short Form (YSQ
      SF). Participants were 833 South Korean and 271 Australian undergraduate
      students. The South Korean sample was randomly divided into two sub-samples.
      Sample A was used for Exploratory Factor Analysis (EFA) and sample B was used for
      Confirmatory Factor Analysis (CFA). EFA for the South Korean sample revealed a 13
      factor solution to be the best fit for the data, and CFA on the data from sample
      B confirmed this result. CFA on the data from the Australian sample also revealed
      a 13-factor solution. The overall scale of the YSQ-SF demonstrated a high level
      of internal consistency in the South Korean and Australian groups. Furthermore,
      adequate internal consistencies for all subscales in the South Korean and
      Australian samples were demonstrated. In conclusion, the results showed that YSQ
      SF with 13 factors has good psychometric properties and reliability for South
      Korean and Australian University students. Korean samples had significantly
      higher YSD scores on most of the 13 subscales than the Australian sample.
      However, limitations of the current study preclude the generalisability of the
      findings to beyond undergraduate student populations.

PMID- 16650483
TI  - Defect of toll-like receptor 9-mediated activation in NC/Nga mouse macrophages.
AB  - Toll-like receptors (TLRs) control activation of adaptive immune responses by
      antigen-presenting cells (APCs). In this study, we examined TLR9-mediated
      activation in NC/Nga mice, an animal model for human atopic dermatitis. NC/Nga
      mouse macrophages produced significantly less TNF-alpha than did BALB/c mouse
      macrophages in response to CpG oligonucleotide (ODN). In addition to defective
      TLR9-mediated TNF-alpha production, phosphorylation of ERK1,2 and p38 was rapidly
      diminished after 60 min of CpG ODN stimulation, whereas phosphorylation of these
      molecules was sustained until 60 min in BALB/c mice. Furthermore, phosphorylation
      of c-Jun N-terminal kinase (JNK) was not observed in NC/Nga mouse macrophages. In
      contrast, B cells and dendritic cells (DCs) from NC/Nga mice showed normal
      responses to CpG ODN stimulation. The expression level of TLR9 in NC/Nga mouse
      macrophages was significantly lower than that in BALB/c mouse macrophages,
      whereas levels of TLR9 expression in B cells and DCs in NC/Nga mice were the same
      as those in BALB/c mice. These results suggest that defective TLR9-mediated
      activation in NC/Nga mouse macrophages contributes to the reduction of TLR9
      expression levels.

PMID- 16650484
TI  - Subglottic cysts in children: a 10-year review.
AB  - Subglottic cysts are associated with prematurity and periods of early neonatal
      intubation and are a rare cause of infant stridor. In this study we analyse our
      experience of this rare but important problem. We discuss the aetiology,
      diagnosis and management of subglottic cysts. We carried out a retrospective
      review of all cases of subglottic cysts presenting to the otorhinolaryngology
      department at the Leeds teaching hospitals trust during the period between 1995
      and 2005. In total seven patients were identified. A retrospective review of the
      case notes of all patients proven to have subglottic cysts at direct laryngoscopy
      and bronchoscopy was undertaken. Seven patients were identified, four males and
      three females. Five were born premature (24-31 weeks). All were intubated with
      average intubation period of 20.6 days. Six of our patients' underwent endoscopic
      marsupialisation using cup forceps and one with a contact diode laser. Two
      patients had recurrence of the cyst and had a repeat of endoscopic
      marsupialisation. This study highlights the associated risk of neonatal
      intubation with the risk of formation of subglottic cysts, and the need for early
      diagnosis and appropriate treatment to avoid unnecessary morbidity.

PMID- 16650485
TI  - Pediatric adenoidectomy: what is the effect of obstructive symptoms on the
      likelihood of future surgery?
AB  - OBJECTIVE: Determine if pediatric patients undergoing adenoidectomy for
      obstruction have an increased likelihood of undergoing eventual tonsillectomy
      and/or second adenoidectomy over extended follow-up. METHODS: Retrospective
      cohort study within the ambulatory surgery component of a tertiary children's
      hospital. Exclusion criteria consisted of the presence of significant co-morbid
      conditions (obesity, craniofacial syndrome, cerebral palsy, etc.) and less than 1
      year of post-adenoidectomy follow-up. The study population included 100 children
      (mean age=3.9 years, range 0.9-15 years) randomly selected from a financial
      billing database undergoing adenoidectomy either with pre-operative obstructive
      symptoms (OB n=52) or without pre-operative obstructive symptoms (NOB n=48) with
      a minimum of 1 year of retrospective follow-up. Electronic records were searched
      for subsequent surgery (tonsillectomy and/or revision adenoidectomy). RESULTS:
      Overall, 29 of 100 children (29%) underwent subsequent surgery (tonsillectomy
      and/or revision adenoidectomy) over an average of 3.46 years (range 1.0-6.59
      years) retrospective follow-up. Children in the OB group were three times more
      likely (age, sex adjusted odds ratio=3.03, 95% confidence interval =1.18-7.78
      p=0.021) than children in the NOB group to require tonsillectomy or second
      adenoidectomy. Age less than 2 years at time of initial adenoidectomy also
      suggested an increased likelihood of subsequent surgery. CONCLUSION: Children
      undergoing adenoidectomy with obstructive symptoms are more likely to require
      eventual tonsillectomy and/or second adenoidectomy than those undergoing
      adenoidectomy without obstruction. However, the low absolute likelihood of future
      surgery precludes a generalized recommendation for tonsillectomy in these
      children.

PMID- 16650486
TI  - Rapid identification of non-essential genes for in vitro replication of Marek's
      disease virus by random transposon mutagenesis.
AB  - Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that induces
      rapid-onset T-cell lymphomas in poultry. The MDV genome encodes more than 100
      genes. However, the role of many of these genes in virus replication is not
      known. The construction of an infectious bacterial artificial chromosome (BAC)
      clone of the highly oncogenic RB-1B strain of MDV has been described previously.
      Virus reconstituted from the BAC clone induced rapid-onset lymphomas in chickens
      very similar to the wildtype viruses. In this paper, the construction of a high
      density random transposon-insertion mutant library of the RB-1B BAC clone using a
      high throughput in vitro transposon mutagenesis technique is described.
      Furthermore a PCR screening method, using primers specific for the transposon
      sequence and the MDV gene(s) of interest, was developed for the rapid
      identification of specific insertion mutants. The application of the screening
      method to identify some of the non-essential genes for MDV replication in vitro
      is described.

PMID- 16650487
TI  - Development of a semi-nested PCR using degenerate primers for the generic
      detection of small ruminant lentivirus proviral DNA.
AB  - A PCR assay was developed for the reliable detection of small ruminant lentivirus
      (SRLV) proviral DNA. The method involved the use of degenerate deoxyinosine
      substituted primers and a second semi-nested PCR step that increased the
      polyvalency and sensitivity of the detection, respectively. Primers were designed
      from the pol gene conserved motifs of 85 SRLV isolates and were evaluated using
      different SRLV isolates together with Maedi-Visna virus (MVV) and caprine
      arthritis-encephalitis virus (CAEV) reference strains. The method successfully
      detected SRLV proviral DNA in total DNA extracts originating from whole blood
      samples, separated peripheral blood mononuclear cells (PBMCs) and tissue
      cultures. The semi-nested PCR was compared with the agar gel immunodiffusion test
      and proved to be highly sensitive, specific and capable of detecting many SRLV
      variants in infected or suspect animals. Therefore, it would be useful in the
      diagnosis of natural SRLV infections, in eradication programs and epidemiological
      studies. Whole blood samples can be used directly, thus alleviating the need for
      PBMC separation, and thereby enables a simple, fast and cost-effective analysis
      of a large number of samples.

PMID- 16650488
TI  - A single tube RT-PCR assay for the detection of mosquito-borne flaviviruses.
AB  - Mosquito-borne flaviviruses include several important agents of human disease and
      have provided striking examples of emerging infections. In this study we present
      the design and validation of a single tube RT-PCR assay using a pair of consensus
      primers for the detection of mosquito-borne flaviviruses. Sequencing of the
      amplicons permits the species identification. The assay was validated using RNA
      from the yellow fever virus vaccine strain and from representative strains of
      dengue viruses 1, 2, 3 and 4, West Nile virus, Kunjin virus (a clade of West Nile
      virus), and St. Louis encephalitis virus.

PMID- 16650489
TI  - Antiviral properties of new arylsulfone derivatives with activity against human
      betaherpesviruses.
AB  - Based on our previous experience with arylsulfone derivatives displaying
      antiherpetic activity, we synthesized several analogues in which the sulfonyl
      group is part of a bicyclic structure. The benzene-fused derivative 2H-3-(4
      chlorophenyl)-3,4-dihydro-1,4-benzo-thiazine-2-carbonitrile 1,1-dioxide and its
      thiophene-fused analogue were shown to have favorable activity and selectivity
      against the betaherpesviruses human cytomegalovirus (HCMV) and human herpesvirus
      6 (HHV-6) and 7 (HHV-7). The benzene-fused derivative retained its anti-HCMV
      activity when evaluated against virus strains resistant to foscarnet,
      ganciclovir, and/or cidofovir. The compound conferred >or=95% inhibition of viral
      DNA synthesis in HHV-6-infected cells. RT-PCR analysis of immediate-early, early
      and late gene products revealed that this arylsulfone compound acts at a step
      preceding late gene expression, and coinciding with the inhibition exerted by
      foscarnet. No inhibitory effect was seen in an enzyme assay for DNA elongation
      catalyzed by the HCMV or HHV-6 DNA polymerase catalytic subunit. The arylsulfone
      derivatives had no effect on the functional interaction between the catalytic
      subunit of HCMV DNA polymerase and its accessory protein, nor did they disrupt
      the physical interaction between the two proteins. We conclude that these
      arylsulfone derivatives represent new betaherpesvirus inhibitors with a novel
      mode of action that results in indirect inhibition of viral DNA synthesis.

PMID- 16650490
TI  - Comparison of the prognostic value of cardiopulmonary exercise testing between
      male and female patients with heart failure.
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPX) clearly holds prognostic value
      in the heart failure (HF) population. Studies investigating the prognostic value
      of CPX in individuals with HF have consistently examined predominantly male
      groups. The purpose of the present study was to examine the prognostic value of
      CPX in a female HF group. METHODS: Seventy-five female and 337 male subjects
      diagnosed with HF participated in this study. The ability of peak oxygen
      consumption (VO(2)) and the minute ventilation/carbon dioxide production
      (VE/VCO(2)) slope to predict cardiac-related events were assessed. RESULTS: In
      the year following CPX, the female group suffered 26 cardiac-related events (8
      deaths/18 hospitalizations), while the male group suffered 89 cardiac-related
      events (20 deaths/69 hospitalizations). The hazard ratios for peak VO(2) and the
      VE/VCO(2) slope were 4.0 (95% confidence interval: 2.6-6.1, p<0.001) and 4.2 (95%
      confidence interval: 2.7-6.6, p<0.001) in the male group and 3.8 (95% confidence
      interval: 1.7-8.5, p<0.001) and 4.3 (95% confidence interval: 1.8-9.8, p<0.001)
      in the female group. In both the male and female groups, Cox multivariate
      analysis revealed VE/VCO(2) slope was the strongest predictor of cardiac-related
      events while peak VO(2) added significant predictive value and was retained in
      the regression. CONCLUSION: The results of the present study indicate that the
      prognostic value of peak VO(2) and the VE/VCO(2) slope are similar in men and
      women diagnosed with HF. In both men and women, the prognostic power of the
      VE/VCO(2) slope is greater than that of peak VO(2).

PMID- 16650491
TI  - Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Several studies have shown beneficial effects of eplerenone in
      hypertension and left ventricular dysfunction, but its action on cardiac and
      vascular changes secondary to blood pressure elevation are not clear yet.
      METHODS: Twenty-five male spontaneously hypertensive rats (SHR) were assigned
      into five groups: young SHR (16 weeks), control SHR (22 weeks), and SHR treated
      by eplerenone (50 mg/kg/day), enalapril (10 mg/kg/day) or eplerenone+enalapril
      during 6 weeks. Five Wistar male rats were used as reference group. Cardiac
      structure and aorta were analyzed by stereology and image analysis. RESULTS: The
      raise of blood pressure (202+/-3 mm Hg in control SHR) was significantly
      attenuated by eplerenone (169+/-2 mm Hg) or enalapril (170+/-2 mm Hg, P<0.001
      versus control SHR), and more intensely by combined therapy (160+/-2 mm Hg,
      P<0.01 versus eplerenone or enalapril). The number of cardiomyocytes in left
      ventricle was preserved in enalapril group (35,660+/-910 versus 16,220+/
      730x10(3) in control SHR, P<0.01) but more significantly in eplerenone, alone or
      combined, groups (38,380+/-439 and 38,660+/-374x10(3), respectively, P<0.001
      versus control). The increased connective tissue volume density (35.8+/-1.2%)
      noted in the left ventricle of control SHR was significantly attenuated by
      eplerenone (7.4+/-0.8%), enalapril (8.0+/-0.6%) or eplerenone+enalapril (6.0+/
      1.1%, P<0.01 treated versus control SHR). Media-to-lumen ratio of intramyocardial
      arteries was reduced by enalapril, but more significantly by eplerenone alone or
      combined with enalapril. The increase of media cross-sectional area of aorta in
      control SHR was attenuated by eplerenone and/or enalapril. CONCLUSIONS:
      Eplerenone is effective in attenuating cardiovascular remodeling in SHR,
      confirming the important role of aldosterone in this process.

PMID- 16650492
TI  - A role for matrix metalloproteinase-9 in the hemodynamic changes following acute
      pulmonary embolism.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) modulate vascular contractility and
      may affect acute pulmonary embolism (APE)-induced pulmonary hypertension. We
      examined the effects of the administration of doxycycline (a MMP inhibitor)
      following APE in anesthetized dogs. METHODS: Sham operated dogs (N=5) received
      only saline. APE was induced by intravenous injections of microspheres in amounts
      to increase mean pulmonary artery pressure (MPAP) by 20 mm Hg, and embolized dogs
      received saline (Emb group, N=8), or doxycycline (10 mg/kg, i.v.) 5 or 30 min of
      APE (Emb+Doxy 5 and Emb+Doxy 30 groups, N=9 and 8, respectively). Hemodynamic
      evaluation was performed at baseline and 5-120 after APE. Gelatin zymography of
      MMP-2 and MMP-9 from plasma samples was performed. RESULTS: No significant
      hemodynamic changes were found in Sham animals. Embolization increased MPAP by
      218+/-16% and the pulmonary vascular resistance index (PVRI) by 289+/-42% in Emb
      group (both P<0.05). Doxycyline increased the cardiac index by 24+/-5% and
      reduced PVRI by 23+/-4% 120 min of APE in Doxy 30+Emb group. In addition,
      doxycyline reduced MPAP and PVRI 30 min after APE with maximum effects seen 120
      min after APE (25+/-4% decrease in MPAP and 33+/-6% decrease in PVRI; both
      P<0.05) in Doxy+5 group. Plasma pro-MMP-9 and MMP-9 levels increased only in Emb
      group and MMP-2 remained unaltered. CONCLUSIONS: Our study shows that doxycycline
      attenuates APE-induced pulmonary hypertension, and indicates that MMP-9 has a
      role in APE-induced pulmonary hypertension. MMP-9 may be a pharmacological target
      in APE.

PMID- 16650493
TI  - Microbial ecology to manage processes in environmental biotechnology.
AB  - Microbial ecology and environmental biotechnology are inherently tied to each
      other. The concepts and tools of microbial ecology are the basis for managing
      processes in environmental biotechnology; and these processes provide interesting
      ecosystems to advance the concepts and tools of microbial ecology. Revolutionary
      advancements in molecular tools to understand the structure and function of
      microbial communities are bolstering the power of microbial ecology. A push from
      advances in modern materials along with a pull from a societal need to become
      more sustainable is enabling environmental biotechnology to create novel
      processes. How do these two fields work together? Five principles illuminate the
      way: (i) aim for big benefits; (ii) develop and apply more powerful tools to
      understand microbial communities; (iii) follow the electrons; (iv) retain slow
      growing biomass; and (v) integrate, integrate, integrate.

PMID- 16650494
TI  - Topographic change in ERP due to discrimination of geometric figures in the
      peripheral visual field.
AB  - The present study examined the neurophysiological aspects of discrimination of
      geometric figures with different eccentricities. In the behavioral experiment, a
      circle and 3 geometric polygons (square, hexagon, or octagon) were presented for
      300 ms at quadrant locations. The eccentricity was changed from 2 degrees to 16
      degrees at 2 degrees intervals. The participants (10 adults) were instructed to
      fixate the center of the CRT and find the circle among the polygons. In the
      neurophysiological experiment, 4 identical stimuli (squares, hexagons, octagons,
      or circles) were presented at an eccentricity of 4 degrees, 8 degrees, or 12
      degrees. Discrimination performance in the periphery declined when the angularity
      of the polygons increased. ERP components at 80 ms (P1 with posterior positivity)
      and 140 ms (N1 with posterior negativity) were observed regardless of the
      eccentricity or shape of the stimuli. N1 lasted longer as eccentricity increased.
      P2 with posterior positivity at 200 ms became blurred in the periphery, except
      for squares. The topography of N1 and P2 changed, depending on the retinal
      stimulus location; it was influenced by the angularity of the geometric figures
      in the peripheral visual field. Cerebral processing concerned with N1 and P2
      might play an important role in the perception and recognition of visual objects
      in the peripheral visual field.

PMID- 16650495
TI  - Distinct mechanisms for planning keypress and reaching responses: a developmental
      study.
AB  - This study examined developmental effects in the ability to use precue
      information for the planning of keypress and reaching responses. Participants
      from four age groups (7, 9, 13, and 21 year olds) performed a spatial precuing
      task either by pressing one of four response keys (keypress task) or by reaching
      directly toward one of the four target locations on the screen (reaching task).
      Reaction time data revealed striking age differences in the ability to use
      advance information in the keypress task, not in the reaching task. This
      dissociation confirms the hypothesis that distinct and separate mechanisms govern
      the planning of indirect keypress and direct reaching responses.

PMID- 16650496
TI  - K(+)-evoked [(3)H]-norepinephrine release in human brain slices from epileptic
      and non-epileptic patients is differentially modulated by gabapentin and
      pinacidil.
AB  - The modulation of K(+)-evoked [(3)H]-norepinephrine ([(3)H]-NE) release by
      gabapentin (GBP) and pinacidil (PIN), a known K(ATP) agonist, was examined in
      human brain slices. We compared the pharmacological effects on NE-release in
      human epileptic neocortex and epileptic hippocampus to non-epileptic neocortex.
      GBP (100 microM) decreased [(3)H]-NE release by 22% in non-epileptic neocortical
      slices, whereas this inhibition was absent in slices from epileptic hippocampus
      and epileptic neocortex. PIN (10 microM) also reduced [(3)H]-NE release by 30% in
      non-epileptic neocortical slices and only by 5% in epileptic hippocampal slices.
      The blockade of voltage-gated calcium channels by omega-conotoxins MVIIA and
      MVIIC (0.1 microM) reduced [(3)H]-NE release in epileptic and non-epileptic
      neocortical slices to the same extend. The data show a marked reduction in K(+)
      evoked [(3)H]-NE release by GBP and PIN in epileptic hippocampus and neocortex,
      suggesting an alteration of K(ATP) channel function, whereas the effects of the
      calcium channel modulators omega-conotoxins MVIIA and MVIIC are similar in both
      epileptic and non-epileptic neocortex.

PMID- 16650497
TI  - Time course analysis of tyrosine hydroxylase and angiotensinogen mRNA expression
      in central nervous system of rats submitted to experimental hypertension.
AB  - Catecholaminergic and angiotensinergic systems are involved in the neural control
      of blood pressure. The present study analysed the expression of tyrosine
      hydroxylase (TH), a key enzyme for catecholamine synthesis and of angiotensinogen
      (AGT), the precursor of angiotensin II (Ang II), in areas of the central nervous
      system (CNS) involved with cardiovascular regulation such as nucleus tractus
      solitarius (NTS), ventrolateral medulla (VLM), locus coeruleus (LC) and
      hypothalamic paraventricular nucleus (PVN) 2 h, 3 and 7 days after aortic
      coarctated hypertensive rats. In situ hybridization, was employed for the
      analysis of messenger RNA (mRNA) expression with anatomical resolution. No
      changes were seen in TH and AGT mRNA expression in the analysed areas 2 h and 3
      days after aortic coarctation when compared to the respective sham group. TH mRNA
      expression was increased in the NTS and LC of rats 7 days after coarctation
      hypertension when compared to sham rats. Time course analysis, showed an increase
      in TH mRNA expression in the NTS 7 days after aortic coarctation when compared to
      2 h and 3 days groups, as well as an increase in LC 3 days and 7 days following
      coarctation hypertension in comparison with the 2 h group. Analysis of AGT mRNA
      in the NTS expression revealed a decrease at 3 days, followed by an increase in
      mRNA expression 7 days following coarctation hypertension when compared to the
      sham group. Time course analysis, showed an increase in AGT mRNA expression in
      the NTS 7 days after coarctation when compared to 2 h and 3 days groups. The
      results show that TH and AGT mRNA expression changes during the different phases
      of experimental hypertension, suggesting that the noradrenaline (NOR) and
      angiotensin II (Ang II) might participate in the modulation/maintenance of
      coarctation hypertension.

PMID- 16650498
TI  - Dehydrogenation of ribitol with Gluconobacter oxydans: production and stability
      of L-ribulose.
AB  - l-Ribulose is an important chiral lead molecule used for the synthesis of, among
      others, l-ribose, a high-value rare sugar used in the preparation of antiviral
      drugs. These drugs--nucleoside-analogues--gain importance in the treatment of
      severe viral diseases, like those caused by the HIV or hepatitis virus. In this
      study, factors that may have an impact on l-ribulose production with
      Gluconobacter oxydans and on the stability of l-ribulose were investigated. A
      bioconversion-type process, using washed resting cells, was chosen to produce l
      ribulose from ribitol. In this process, the cell production and bioconversion
      phase were separated. The former was first optimized and a maximum cell mass of
      1.5 g CDWL(-1) could be produced. For the bioconversion phase, the aeration level
      of the system proved to be one of the most critical factors; a maximal production
      rate of 15.7 g L(-1)h(-1) or 5.9 g(g CDW)(-1)h(-1) of l-ribulose could be
      reached. Furthermore, resting cells were found capable of completely converting
      ribitol solutions of up to 300 g L(-1) within 30 h, although the kinetics
      indicated a rather low affinity of the dehydrogenase enzymes for the substrate.

PMID- 16650499
TI  - Cost-minimization analysis for Portugal of five doublet chemotherapy regimens
      from two phase III trials in the treatment of advanced non-small cell lung
      cancer.
AB  - OBJECTIVES: Economic evaluations of chemotherapy regimens for stage IIIB or IV
      non-small cell lung cancer (NSCLC) have been conducted for many European
      countries, but not for Portugal. This study evaluates the total health care costs
      of five commonly used doublet regimens with similar efficacy results. METHODS:
      Using the methodology reported by Schiller [Schiller JH, Tilden D, Aristides M,
      Lees M, Kielhorn A, Maniadakis N, et al. Restropective cost analysis of
      gemcitabine in combination with cisplatin in non-small cell lung cancer compared
      to other combination therapies in Europe. Lung Cancer 2004;43:101-12], we
      conducted a cost-minimization analysis to compare vinorelbine-cisplatin
      (Vin/Cis), gemcitabine-cisplatin (Gem/Cis), paclitaxel-carboplatin (Pac/Carb),
      docetaxel-cisplatin (Doc/Cis), and paclitaxel-cisplatin (Pac/Cis). The
      perspective was that of the Portuguese National Health Service and included only
      direct medical costs (reimbursed costs plus co-payments): chemotherapy
      acquisition, chemotherapy administration, hospitalizations due to adverse events,
      and other medical resources. Unit costs were drawn from official sources
      (Diagnosis Related Groups and retail/hospital costs) (2003 value [Diagnosis
      Related Groups (DRG) published at Diario da Republica; 2003]). Resource use was
      estimated from two multicenter randomized phase III trials [Comella P, Frasci G,
      Panza N, Manzione L, De Cataldis G, Cioffi R, et al. Randomized trial comparing
      cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or
      cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim
      analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J
      Clin Oncol 2000;18:1451-7; Schiller JH, Harrington D, Belani CP, Langer C,
      Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced
      non-small-cell lung cancer. N Engl J Med 2002;346:92-8]. A time horizon of a full
      course of therapy was adopted. One-way sensitivity analyses were performed.
      RESULTS: The least and the most costly chemotherapy regimens were Gem/Cis and
      Pac/Carb, respectively. Total mean cost per patient was estimated at euro7083 for
      Gem/Cis and euro10,008 for Pac/Carb, a mean cost savings of euro2925 per patient
      for Gem/Cis. The differences were mainly due to the higher chemotherapy
      acquisition costs of Pac/Carb than for Gem/Cis. Gem/Cis was less costly in all
      sensitivity analyses except when 100% inpatient chemotherapy administration was
      assumed. CONCLUSION: Gem/Cis should be considered as a cost-saving alternative to
      the other four regimens in treating NSCLC patients in Portugal.

PMID- 16650500
TI  - Mobilisation of nutrients and transport via the xylem sap in a shrub (Ligustrum
      ovalifolium) during spring growth: N and C compounds and interactions.
AB  - In open-field soilless culture there can be great deal of leaching, particularly
      in rainy springs. Ligneous plants have the capacity to store large quantities of
      nutrients in perennial organs. Knowledge of the plant's internal nutrient
      mobilisation during spring to supply growing organs could lead to reduction of
      fertiliser application. To quantify the fraction of storage mobilisation
      available for growth of new organs during spring, Ligustrum ovalifolium shrubs
      were grown for 2 years with or without fertilisation in the second spring.
      Nitrogen (N) absorption and N and carbon (C) mobilisation from storage were
      followed during spring growth via the sap quality. A mathematical combination of
      the sap composition with flow velocity provided the transported quantities of N
      and C. Nitrogen and C mobilisation towards new shoots took place during all the
      spring growth from bud break onwards. In unfertilised plants, C was mobilised
      primarily as sugars (stachyose, mannose and sucrose) and starch. In fertilised
      plants, the same sugars were transported in the xylem sap, but at lower
      concentrations. Stachyose concentration was lower in fertilised than in
      unfertilised plants and decreased during spring growth. Nitrogen was transported
      in the xylem sap mainly as amino acids in both fertilisation treatments.
      Glutamine was the predominant form at bud break and during shoot elongation. In
      fertilised plants, arginine became predominant after shoot elongation, and was
      related to low C availability. The interactions of N with C are discussed;
      specifically, insufficient availability of N limits the use of C, more of which
      is directed to aerial organs by sap flow.

PMID- 16650501
TI  - Association of broad-spectrum antibiotic use with faecal carriage of
      oxyiminocephalosporin-resistant enterobacteriaceae in an intensive care unit.
AB  - The link between administration of antibiotics and detection of third-generation
      cephalosporin-resistant (TGCR) enterobacteriaceae in faeces was studied in
      patients in a burns intensive care unit (ICU). The presence of extended-spectrum
      beta-lactamase producers was also determined in these isolates. At least two
      rectal swab samples were taken from 43 of 72 patients admitted to the ICU from
      January 1998 to June 1999. Antibiotic resistance tests were performed for all
      isolated enterobacteriaceae using the methods of the National Committee for
      Clinical Laboratory Standards. Only 10 out of 30 antibiotic-treated patients
      showed TGCR enterobacteriaceae in faeces. Fisher's exact test showed a
      relationship between the administration of oxyiminocephalosporins (third
      generation cephalosporins) (P=0.002) or carbapenems (P=0.003) and the isolation
      of TGCR enterobacteriaceae from faeces. The administration of
      oxyiminocephalosporins led to the selection of resistant strains in the faecal
      flora.

PMID- 16650502
TI  - The prevalence of resistance to silver in a Burns unit.

PMID- 16650503
TI  - Incidence and characterization of Clostridium perfringens isolated from
      antibiotic-associated diarrhoeal patients: a prospective study in an Indian
      hospital.
AB  - Clostridium perfringens has been reported as causing between 2-15% of all cases
      of antibiotic-associated diarrhoea (AAD), and may be diagnosed by detection of
      enterotoxin in faeces. A prospective study comprising 150 diarrhoeal patients and
      100 non-diarrhoeal controls was undertaken to assess the incidence of C.
      perfringens-associated diarrhoea in an Indian hospital. Methods used included C.
      perfringens culture, reverse passive latex agglutination (RPLA) and enzyme-linked
      immunosorbent assay (ELISA) for detection of enterotoxin, and polymerase chain
      reaction (PCR) assay for the presence of enterotoxin gene. Attempts were made to
      type the isolates by multiplex PCR. Of the 150 diarrhoeal stool samples tested,
      13 were culture positive. Of these, four were positive for C. perfringens
      enterotoxin by RPLA, two were positive by PCR and two were positive by RPLA and
      ELISA. Twenty-seven samples were positive for culture of C. perfringens in non
      diarrhoeal controls but none were positive for enterotoxin either by RPLA or by
      PCR. The average incidence of C. perfringens AAD using these methods was 2.6%.
      Toxin typing showed that all the isolates belonged to type A. To conclude, the
      relatively low incidence of toxigenic C. perfringens suggests that
      enterotoxigenic C. perfringens is not a major cause of AAD in this population.

PMID- 16650504
TI  - Tolerance and acceptability of 14 surgical and hygienic alcohol-based hand rubs.
AB  - Tests were performed under working practice conditions to measure the tolerance
      and acceptability of commercially available hand rubs with proven efficacy. The
      products were compared with those in current use at the Hospices Civils de Lyon
      for surgical hand disinfection (Sterillium) and hygienic hand disinfection
      (Purell) to obtain information for public sector purchases. The 12 test products
      were Alcogel H, Assanis Pro, Clinogel, Dermalcool, Manugel Plus, Manugel Plus
      NPC, Manurub Liquid, Manurub Gel, Purell 85, Spitacid, Spitagel and Sterillium
      Gel. They were tested from mid-November to mid-April over four periods of three
      weeks, separated by two-week intervals during which the customary product was re
      introduced. Participation of hospital wards and theatres was voluntary. Skin
      dryness and irritation were scored before and after each test period.
      Acceptability and ease of use were assessed by means of a questionnaire. Among
      the eight surgical hand rubs, only Manurub Liquid, Manurub Gel and Manugel Plus
      NPC did not cause significantly more dryness and irritation than Sterillium. For
      the 10 hygienic hand rubs, differences were noted depending upon the test period.
      Overall, Assanis Pro, Clinogel, Purell 85 and Sterillium Gel did not cause
      significantly more dryness and irritation than Purell. However, over the (colder)
      first three test periods, Assanis Pro and Sterillium Gel caused more irritation
      and Purell 85 caused more dryness than Purell. Responses to the questionnaires on
      acceptability indicated that users preferred their customary hand rubs
      (Sterillium and Purell). As these field tests involving many participants did not
      identify any superior products, previous purchase orders were renewed.

PMID- 16650505
TI  - Needlestick injuries during medical training.
AB  - Medical students are at risk of acquiring infections caused by needlestick
      injuries, although it is unknown when needlestick injuries are most likely to
      occur during medical training. The aim of this study was to define high-risk
      periods over the course of medical training. A cross-sectional study was
      conducted among medical students in the first, third, fourth and fifth years of
      training at two medical schools in Munich. Overall, 1317 (85%) students returned
      a questionnaire on demographic data, vaccination status against hepatitis B,
      lifetime prevalence of needlestick injuries, level of knowledge about measures
      after such accidents, and transmission risks. Lifetime prevalence of needlestick
      injuries was 23%, ranging from 12% in first year students to 41% in fourth year
      students. These accidents happened most commonly during medical internships,
      especially during blood-taking practices; an activity that usually starts during
      the third year of training. The frequency of respondents not vaccinated against
      hepatitis B also varied between first (21%) and fourth (6.6%) year students.
      Needlestick injuries occur frequently and early on in medical training. In order
      to decrease the risk of preventable infections, complete coverage of vaccination
      against hepatitis B should be achieved early in medical training.

PMID- 16650506
TI  - Endoscope disinfection using chlorine dioxide in an automated washer-disinfector.
AB  - Although 2% glutaraldehyde is often the first-line agent for endoscopic
      disinfection, its adverse reactions are common among staff and it is less
      effective against certain mycobacteria and spore-bearing bacteria. Chlorine
      dioxide is a possible alternative and an automated washer-disinfector fitted with
      this agent is currently available. This study was conducted to evaluate the
      effectiveness of chlorine dioxide in endoscopic disinfection after upper
      gastrointestinal examination. In vitro microbicidal properties of chlorine
      dioxide solutions were examined at high (600 ppm) and low (30 ppm) concentrations
      against various microbes including Pseudomonas aeruginosa, Helicobacter pylori,
      Mycobacterium avium-intracellulare and Bacillus subtilis in the presence or
      absence of bovine serum albumin (BSA). Immediately following endoscopic
      procedures and after application to the automated reprocessor incorporating
      chlorine dioxide at 30 ppm for 5 min, endoscopic contamination with infectious
      agents, blood, H. pylori ureA gene DNA and HCV-RNA was assessed by cultivation,
      sensitive test tape, polymerase chain reaction (PCR) and reverse transcriptase
      PCR analysis, respectively. Chlorine dioxide at 30 ppm has equivalent
      microbicidal activity against most microbes and faster antimicrobial effects on
      M. avium-intracellulare and B. subtilis compared with 2% glutaraldehyde, but
      contamination with BSA affected the microbicidal properties of chlorine dioxide.
      Endoscopic contamination with microbes, blood and bacterial DNA was eliminated
      after application of the automated reprocessor/chlorine dioxide system. Thus,
      chlorine dioxide is a potential alternative to glutaraldehyde. The use of
      automated reprocessors with compatibility to chlorine dioxide, coupled with
      thorough pre-cleaning, can offer effective, faster and less problematic
      endoscopic disinfection.

PMID- 16650507
TI  - Potential use of copper surfaces to reduce survival of epidemic meticillin
      resistant Staphylococcus aureus in the healthcare environment.
AB  - Epidemic meticillin-resistant Staphylococcus aureus (EMRSA) emerged in the early
      1980s with EMRSA-15 and -16 being the most prevalent strains within the UK. MRSA
      transmission between patients is largely via the hands of healthcare workers, and
      contamination of the hospital environment may occur. The objective of this study
      was to evaluate the effectiveness of copper and brass to reduce the viability of
      air-dried deposits of three MRSA strains [MRSA (NCTC 10442), EMRSA-1 (NCTC 11939)
      and EMRSA-16 (NCTC 13143)] compared with stainless steel. MRSA and EMRSA
      [10(7)colony-forming units (CFU)] were inoculated on to coupons (1 cm x 1 cm) of
      copper, brass or stainless steel and incubated at either 22 degrees C or 4
      degrees C for various time periods. Viability was determined by resuspending
      removed CFUs and plating out on tryptone soy agar plates in addition to staining
      with the respiratory indicator fluorochrome 5-cyano-2,3-ditolyl tetrazolium. On
      pure copper surfaces, 10(7) MRSA, EMRSA-1 and EMRSA-16 were completely killed
      after 45, 60 and 90 min, respectively, at 22 degrees C. In contrast, viable
      organisms for all three strains were detected on stainless steel (grade 304)
      after 72 h at 22 degrees C. At 4 degrees C, complete kill was achieved on copper
      for all three strains within 6 h. The results demonstrate an antimicrobial effect
      of copper on MRSA, EMRSA-1 and -16 in contrast to stainless steel. Consequently,
      the contemporary application of stainless steel in hospital environments for work
      surfaces and door furniture is not recommended.

PMID- 16650508
TI  - Opposite effects of low and high doses of the gastrin-releasing peptide receptor
      antagonist RC-3095 on memory consolidation in the hippocampus: possible
      involvement of the GABAergic system.
AB  - Although the gastrin-releasing peptide receptor (GRPR) has recently emerged as a
      system importantly involved in regulating memory formation, the role of
      hippocampal GRPRs in memory remains controversial. The present study examined the
      effects of GRPR antagonism on memory consolidation in area CA1 of the
      hippocampus. Male Wistar rats received bilateral infusions of the GRPR antagonist
      [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095; 1, 3, or 10
      microg/side) into the dorsal hippocampus immediately after inhibitory avoidance
      (IA) training. RC-3095 at 1 microg impaired, whereas the dose of 10 microg
      enhanced, 24-h IA retention. A second experiment showed that the RC-3095-induced
      enhancement of memory consolidation was prevented by pretraining infusion of an
      otherwise ineffective dose of the gamma-aminobutyric acid type A (GABA(A))
      receptor agonist muscimol. The results indicate that high doses of GRPR
      antagonists can induce enhancement of memory consolidation in the hippocampus. In
      addition, the memory-enhancing effect of GRPR antagonists might be mediated by
      inhibition of GABAergic transmission.

PMID- 16650509
TI  - The action of urocortins on body temperature in rats.
AB  - The actions of individual urocortins on colon temperature were studied in rats.
      Urocortin 1, urocortin 2 or urocortin 3 was injected into the lateral brain
      ventricle in conscious rats and the colon temperature was measured at different
      times following injection, for up to 6 h. In order to study the possible role of
      prostaglandins, the animals were treated with either a urocortin together with
      the pyrazolone derivative noraminophenazone to inhibit the action of
      cyclooxygenase in initiating hyperthermia, or with noraminophenazone 30 min
      following urocortin administration to act on existing hyperthermia.
      Noraminophenazone was administered intramuscularly in a dose of 50 mg/kg.
      Urocortin 1 caused a dose-related increase in colon temperature, maximal action
      being observed at a dose of 2 microg with the maximal increase in body
      temperature at 4 h. Noraminophenazone prevented the urocortin-induced increase in
      colon temperature and attenuated the already existing elevated body temperature.
      Somewhat similar action was observed with urocortin 2. However, following
      treatment with 0.5 or 1.0 microg urocortin 2, the action was already over at 2 h,
      whereas 2 microg increased the colon temperature steadily, with a maximum at 4 h.
      Noraminophenazone blocked or diminished the action of urocortin 2. Urocortin 3 in
      a dose of 1 microg was the most effective in increasing the colon temperature;
      the maximal effect was observed at 2 h. Noraminophenazone blocked the development
      of urocortin 3-induced hyperthermia, or attenuated it when the hyperthermia was
      already present. The results demonstrated that urocortin 1, 2 or 3 caused
      increases in body temperature when injected into the lateral brain ventricle,
      though the optimal dose and the duration of hyperthermia differed for the
      individual urocortins. The cyclooxygenase inhibitor blocked or diminished the
      action of these urocortins, indicating the involvement of prostaglandins in
      urocortin-induced hyperthermia.

PMID- 16650510
TI  - Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel
      cyano- and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes,
      thieno-benzofurans, benzo-dithiophenes and their acyclic precursors.
AB  - As a part of the research on the improvement of an alternative to conventional
      photodynamic therapy by light-induced formation of intercalators, we synthesized
      a series of novel heterocyclic compounds and their acyclic precursors. We now
      report details about their synthesis/characterization in respect to their
      potential of photoinduced cyclization, interactions with DNA and inhibition of
      the tumor cell growth in vitro. Among studied compounds only amidino-furyl
      substituted phenyl acrylates were efficiently converted to the corresponding
      naphthofuranes, while their thiophene analogues, all non-charged derivatives and
      amidino-phenyl-substituted analogues didn't show acceptable photoconversion. The
      significantly stronger antiproliferative activity of cyclic analogues could be
      correlated to the property of these molecules to intercalate into DNA. The
      acyclic molecules did not show any interaction with DNA, correlating with the
      inferior biological activity, except for one cyano-bearing molecule.

PMID- 16650511
TI  - [Extradigestive manifestations of chronic intestinal inflammatory diseases].

PMID- 16650512
TI  - Multivalent norovirus vaccines induce strong mucosal and systemic blocking
      antibodies against multiple strains.
AB  - Noroviruses are important agents of human gastroenteritis characterized by
      extensive sequence variation in the major capsid structural protein that likely
      encodes critical antigenic determinants of protective immunity. The lack of an
      infection model has limited detailed characterizations of viral antigenic
      relationships and identification of the essential components for protective
      immunity. This information would contribute to efficacious vaccine design against
      a broad array of norovirus strains. To understand the extent of heterotypic
      norovirus antibody specificity to inter- and intra-genogroup strains and its
      applicability to vaccine design, we collected sera from humans infected with
      different norovirus strains and from mice inoculated with alphavirus vectors
      expressing strain-specific recombinant norovirus-like particles (VLPs). We used
      VLPs that were assembled from Norwalk virus (NV), Hawaii virus (HV), Snow
      Mountain virus (SM) and Lordsdale virus (LV) as antigens to define and compare
      heterotypic antibody responses in humans and mice. We also examined if these
      heterotypic antibodies could block specific binding of ABH histo-blood group
      antigens, putative receptors for norovirus binding and entry, to norovirus VLPs.
      Furthermore, we examined the effect of multivalent inocula on the specificity,
      titer, and ligand blockade properties of systemic and mucosal norovirus-specific
      antibodies in mice. Our studies suggest that infection with one of several
      different genogroup I (GI) strains in humans induces heterotypic antibodies that
      block NV binding to ABH antigens, although comparable findings were not evident
      following infection with genogroup (GII) strains. Additionally, inoculating mice
      with vaccine cocktails encoding multiple norovirus VLPs enhances heterotypic and
      ligand attachment-blocking antibody responses against the LV strain not included
      in the cocktail. These data suggest that multivalent vaccination may provide
      better protection from a broader range of noroviruses than monovalent
      vaccination.

PMID- 16650513
TI  - Social environment and physical activity: a review of concepts and evidence.
AB  - The rapidly growing and evolving literature on the social environment and its
      influence on health outcomes currently lacks a clear taxonomy of dimensions of
      the social environment and the differing mechanisms through which each influences
      health-related behavior. This paper identifies five dimensions of the social
      environment-social support and social networks, socioeconomic position and income
      inequality, racial discrimination, social cohesion and social capital, and
      neighborhood factors-and considers each in the context of physical activity to
      illustrate important differences between them. Increasing the specificity of
      terminology and methods in social environmental research on health will enable
      more systematic inquiry and accelerate the rate of scientific discovery in this
      important area.

PMID- 16650514
TI  - Individual, neighborhood, and state-level predictors of smoking among US Black
      women: a multilevel analysis.
AB  - Baseline data from the Black Women's Health Study (BWHS) were analyzed to assess
      the relation of smoking to individual, neighborhood, and state socioeconomic
      characteristics. Data on smoking status and individual socioeconomic
      characteristics were obtained via a self-administered postal questionnaire at
      entry. Neighborhood characteristics of 41,726 never and current smokers were
      obtained by linking participants' addresses with census tract data from the 1990
      US Census. In a multilevel logistic regression model, higher neighborhood poverty
      was associated with increased smoking prevalence after adjusting for age,
      education, marital status, and occupation at the individual level, and percent
      high school graduate, percent college graduate, and percentage Black at the
      neighborhood level. Relative to women residing in neighborhoods with less than 5%
      of the residents below the poverty line, the odds ratio was 1.1 (95% confidence
      interval: 1.0-1.2) for women in neighborhoods with 5-9.9% of the residents below
      the poverty line, 1.3 (1.2-1.4) for women in neighborhoods with 10-19.9% of the
      residents below the poverty line, and 1.6 (1.5-1.8) for women in neighborhoods
      with 20% or more of the residents below poverty. State of residence was also
      significantly associated with prevalence of current smoking. These results
      suggest that contextual factors (at both the neighborhood and state level) play a
      role in Black women's smoking behaviors over and above individual
      characteristics.

PMID- 16650515
TI  - Retaining the meaning of the words religiousness and spirituality: a commentary
      on the WHOQOL SRPB group's "a cross-cultural study of spirituality, religion, and
      personal beliefs as components of quality of life" (62: 6, 2005, 1486-1497).
AB  - Recent years have seen increasing recognition paid to the relation of
      religiousness/spirituality (R/S) to health care and research. This has led to the
      development of more inclusive and trans-culturally validated measurements of R/S.
      This paper comments on the WHOQOL SRPB Group's "A cross-cultural study of
      spirituality, religion, and personal beliefs as components of quality of life"
      (62: 6, 2005, 1486-1497), a recently published paper in Social Science &
      Medicine, and illustrates a possible problem in the measurement of R/S,
      especially as related to the study of mental health outcomes. Some scales have
      included questions about psychological well-being, satisfaction, connectedness
      with others, hopefulness, meaning and purpose in life, or altruistic values as
      part of their measure of R/S. These questions are really tapping indicators of
      mental health, and should not be included in the definition of R/S itself.
      Otherwise, tautology is the result, and it should not be surprising that such
      measures of R/S (defined by questions tapping mental health) are related to
      mental health outcomes.

PMID- 16650516
TI  - Effects of escitalopram on ethanol withdrawal syndrome in rats.
AB  - The present study was designed to investigate the effects of escitalopram, a
      selective serotonin reuptake inhibitor, on ethanol withdrawal syndrome in rats.
      Adult male Wistar rats (266-278 g) were subjects. Ethanol (7.2%, v/v) was given
      to rats by a liquid diet for 21 days. Control rats were pair fed with an
      isocaloric liquid diet containing sucrose as a caloric substitute to ethanol.
      Escitalopram (2.5, 5 and 10 mg/kg) and saline were injected to rats
      intraperitoneally just before ethanol withdrawal. After the second and sixth
      hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs
      that included locomotor hyperactivity, agitation, stereotyped behavior, wet dog
      shakes, tremors and audiogenic seizures were recorded or rated. A second series
      of injections was given 30 min before sixth hour of withdrawal test. Effects of
      escitalopram on the locomotor activities of the naive (no ethanol-dependent) rats
      were also evaluated. Escitalopram (5 mg/kg) reduced the increased stereotyped
      behaviors at the sixth hour of ethanol withdrawal. It inhibited tremors at the
      second hour of ethanol withdrawal at doses of 5 and 10 mg/kg. Escitalopram (2.5
      and 5 mg/kg) also produced some significant attenuations in the incidence of wet
      dog shakes at the second and sixth hours of the observation period. It was found
      ineffective on locomotor hyperactivity, agitation and audiogenic seizures.
      Escitalopram (2.5 and 5 mg/kg) did not cause any significant effect on locomotor
      activities of the naive rats. Our results suggest that acute escitalopram
      treatment has some limited beneficial effects on ethanol withdrawal syndrome in
      rats.

PMID- 16650517
TI  - Retrospective identification of ricin in animal tissues following administration
      by pulmonary and oral routes.
AB  - A previously characterised amplified ELISA for ricin (sensitivity limit
      approximately 200 pgmL(-1)) has been employed to quantify ricin following a novel
      recovery method from selected tissues. Tissue samples from rats dosed by
      pulmonary instillation or orally with ricin were homogenised and treated with an
      elution buffer to extract ricin. This is the first time that ex vivo recovery of
      ricin post exposure following pulmonary or oral challenge has been achieved using
      clinically acceptable sampling methods, with promise in terms of diagnosis for
      the timely implementation of therapy. The toxin was detected and quantified using
      the ELISA in conjunction with pure ricin standards. Extracts from tissues
      sampled, including lung, blood, liver and spleen tested positive for ricin with
      maximum yield in lung associated fractions for pulmonary dosing and liver tissue
      for oral administration. This indicates the potential of lavage and blood
      sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes,
      respectively. Time course analysis at 24 and 48 h also indicated the progression
      of ricin from surfaces of the lung into the lung tissue. Inter-subject variation
      was observed in the case of oral dosing, with data for ricin-treated and vehicle
      control tissues not statistically different in all samples. In addition the oral
      toxicity of the crude ricin administered was found to be higher than expected in
      the rat, based upon published information and an unpublished in house murine
      study.

PMID- 16650518
TI  - John Eccles' studies of spinal cord presynaptic inhibition.
AB  - Presynaptic inhibition is one of many areas of neurophysiology in which Sir John
      Eccles did pioneering work. Frank and Fuortes first described presynaptic
      inhibition in 1957. Subsequently, Eccles and his colleagues characterized the
      process more fully and showed its relationship to primary afferent
      depolarization. Eccles' studies emphasized presynaptic inhibition of the group Ia
      monosynaptic reflex pathway but also included group Ib, II and cutaneous afferent
      pathways, and the dorsal column nuclei. Presynaptic inhibition of the group Ia
      afferent pathway was demonstrated by depression of monosynaptic excitatory
      postsynaptic potentials and inhibition of monosynaptic reflex discharges. Primary
      afferent depolarization was investigated by recordings of dorsal root potentials,
      dorsal root reflexes, cord dorsum and spinal cord field potentials, and tests of
      the excitability of primary afferent terminals. Primary afferent depolarization
      was proposed to result in presynaptic inhibition by reducing the amplitude of the
      action potential as it invades presynaptic terminals. This resulted in less
      calcium influx and, therefore, less transmitter release. Presynaptic inhibition
      and primary afferent depolarization could be blocked by antagonists of GABA(A)
      receptors, implying a role of interneurons that release gamma aminobutyric acid
      in the inhibitory circuit. The reason why afferent terminals were depolarized was
      later explained by a high intracellular concentration of Cl(-) ions in primary
      sensory neurons. Activation of GABA(A) receptors opens Cl(-) channels, and Cl(-)
      efflux results in depolarization. Another proposed mechanism of depolarization
      was an increase in extracellular concentration of K(+) following neural activity.
      Eccles' work on presynaptic inhibition has since been extended in a variety of
      ways.

PMID- 16650519
TI  - Carboplatin-based neoadjuvant treatment with peripheral blood stem cell and
      growth factor support in locally advanced cervical cancer patients with bulky
      metastatic lymph nodes.

PMID- 16650520
TI  - Analysis of human unfertilized oocytes and pronuclear zygotes--correlation
      between chromosome/chromatin status and patient-related factors.
AB  - OBJECTIVE: The objective was to evaluate the relationship between ploidy and
      chromatin status of human unfertilized oocytes/zygotes and infertility history,
      female age, and stimulation regimens. STUDY DESIGN: Two hundred and eighty-nine
      unfertilized oocytes and 63 zygotes were subjected to cytogenetic analysis:
      karyotyping for oocytes and fluorescent in situ hybridization (FISH) analysis for
      zygotes. Ploidy and chromosome/chromatin status were analyzed according to
      stimulation regimen, female age, and infertility history. The correlation
      coefficient was estimated and data were interpreted using a five-grade scale.
      RESULTS: Aneuploidy in karyotyped oocytes (19.7% hyperhaploidy, 18.8%
      hypohaploidy, and 6.3% haploid abnormal) was associated with chromosome
      fragmentation and lesions due to chromosome aging in culture. Premature
      chromosome condensation and cytoskeletal defects were significantly higher in
      unexplained infertility (34.7% and 52.9%, respectively; p<0.05). Chromatin
      quality was most important for successful ploidy analysis of zygotes. FISH
      analysis of abnormal zygotes elucidated genetic aspects of pronuclear number
      aberrations and raised questions about the current selection criteria.
      Abnormalities were found to correlate moderately with stimulation strategy and
      female age and significantly with infertility history. CONCLUSION: Genetic
      analysis of human oocytes and zygotes showed that poor chromatin quality and
      patient-related factors contribute to aneuploidy and pronuclear number
      aberrations.

PMID- 16650521
TI  - Membrane computing: brief introduction, recent results and applications.
AB  - The internal organization and functioning of living cells, as well as their
      cooperation in tissues and higher order structures, can be a rich source of
      inspiration for computer science, not fully exploited at the present date.
      Membrane computing is an answer to this challenge, well developed at the
      theoretical (mathematical and computability theory) level, already having several
      applications (via usual computers), but without having yet a bio-lab
      implementation. After briefly discussing some general issues related to natural
      computing, this paper provides an informal introduction to membrane computing,
      focused on the main ideas, the main classes of results and of applications. Then,
      three recent achievements, of three different types, are briefly presented, with
      emphasis on the usefulness of membrane computing as a framework for devising
      models of interest for biological and medical research.

PMID- 16650522
TI  - Grazers and grass: Monte Carlo simulations.
AB  - To illustrate the interplay between grazers and grass, we present a novel Monte
      Carlo model including grass-island growth, consumption of grass by grazers, and
      birth, migration and death of grazers. The rates of the former and three latter
      processes are assumed to depend on the environment so that the conventional mean
      field approximation does not hold (in particular, the model takes into account
      that grass grows on the grass-island boundaries, and grazers are mobile and
      prefer to stay on the areas covered by grass). Due to the feedback between
      various processes, as expected, the model predicts stable regimes and irregular
      oscillations of the area of the grass islands and grazer population. The patterns
      observed are however different compared to those predicted by conventional Monte
      Carlo prey-predator models. Specifically, there is no tendency for grazers and
      grass to segregate. The mean-field version of the model is briefly discussed as
      well.

PMID- 16650523
TI  - Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in
      hepatocellular carcinoma.
AB  - A high frequency of allelic loss affecting chromosome 8p and a minimal region of
      deletion at p21-22 have been previously reported in hepatocellular carcinoma
      (HCC), suggesting that at least one tumor suppressor gene is present in this
      region. In this study, we assessed whether the angiotensin II AT2 receptor
      interacting protein (ATIP)/mitochondrial tumor suppressor gene (MTUS1), a gene
      newly identified at position 8p22, may be a candidate tumor suppressor gene
      mutated in HCC. We searched for alterations in the 17 coding exons of ATIP/MTUS1
      by means of denaturating high-performance liquid chromatography and sequencing,
      in 51 HCC tumors and 58 cell lines for which loss of heterozygosity status was
      known. Five major nucleotide substitutions were identified, all located in exons
      used by the ATIP3 transcript which is the only ATIP transcript variant expressed
      in liver. These nucleotide variations result in amino-acid substitution or
      deletion of conserved structural motifs (nuclear localisation signal, polyproline
      motif, leucine zipper) and also affect exonic splicing enhancer motifs and
      physiological splice sites, suggesting potential deleterious effects on ATIP3
      function and/or expression.

PMID- 16650524
TI  - Lactoferrin potently inhibits osteoblast apoptosis, via an LRP1-independent
      pathway.
AB  - Lactoferrin induces osteoblast proliferation in vitro and is anabolic to bone in
      vivo. We recently reported that the low-density lipoprotein-receptor-related
      protein 1 (LRP1), a multifunctional member of the LDL receptor family, transduces
      the mitogenic signal activated by lactoferrin. Here we investigate the effects of
      lactoferrin on osteoblast survival. At periphysiological concentrations (1
      10mug/ml), lactoferrin protects both primary rat osteoblastic cells and SaOS2
      cells from apoptosis induced by serum withdrawal. Surprisingly, this effect was
      not sensitive to the LRP1/2 inhibitor receptor-associated protein (RAP). Neither
      did lactoferrin selectively prevent apoptosis in fibroblastic cells expressing
      wild-type LRP1 compared to LRP1-null fibroblasts. Lactoferrin activates PI3
      kinase-dependent Akt signaling in osteoblasts but this effect is neither LRP1
      dependent nor required for lactoferrin-induced cell survival. Lactoferrin
      activates p42/44 MAPK signaling, but inhibiting this process does not abrogate
      its pro-survival actions. These results demonstrate that lactoferrin promotes
      osteoblast survival, an effect that may contribute to its anabolic skeletal
      actions in vivo. Our data also suggest that the molecular mechanisms that
      underpin the ability of lactoferrin to promote cell survival differ fundamentally
      from those which subserve its mitogenic actions, in particular being mediated by
      a distinct cell-membrane-based receptor.

PMID- 16650525
TI  - Modulation of BMAL/CLOCK/E-Box complex activity by a CT-rich cis-acting element.
AB  - The interaction between the BMAL1/CLOCK transcription factor and the cis-acting
      element known as the E-Box is a key event in the regulation of clock and clock
      controlled gene expression. However, the fact that the ubiquitous E-Box element
      sits at the center of a presumably highly discriminating control system generates
      a certain level of puzzlement. Widely spread E-Boxes with a generic sequence
      CANNTG have been associated with expression of genes involved in a host of
      disparate biological processes, including the orchestration of circadian
      physiology. The intriguing specificity of this short DNA consensus element begs
      the hypothesis that its actual circadian properties might be encoded elsewhere,
      e.g., other factors or adjacent sequences. In a previous study, we found evidence
      that a short sequence in the mouse arginine vasopressin (AVP) proximal promoter
      has the ability to confer robust BMAL1/CLOCK responsiveness onto an adjacent E
      Box. Here, we report the systematic analysis of this element. Our findings
      further define the determining features and sequence boundaries of this element,
      establish the effect of the photoperiod upon its interacting protein(s), and
      suggest that its cognate binding activity might be modulated by Zn2+ in a
      peripheral oscillator.

PMID- 16650526
TI  - Human papillomavirus type 77 E7 protein is a weak deregulator of cell cycle.
AB  - Human Papillomavirus type 77 is a skin type found in non-melanoma skin cancers of
      immuno-compromised individuals. Although, the HPV77 E6 oncoprotein has been well
      studied, nothing is known about E7. Studies on mucosal HPV types (e.g. HPV16)
      showed that E7 deregulates the cell cycle by binding to and promoting degradation
      of retinoblastoma protein (pRb). Here, we characterized the impact of HPV77 E7 on
      the cell cycle. We observed that HPV77 E7 associated with pRb with a lower
      affinity than HPV16 E7, promoting weakly its degradation. Although, HPV16 E7 led
      to cellular proliferation and accumulation of the cell cycle inhibitor
      p16(INK4a), both events were not clearly observed in HPV77 E7 cells. Together,
      these data indicate that HPV77 E7 does not efficiently deregulate the cell cycle,
      in contrast to several E7s of mucosal HPV types.

PMID- 16650527
TI  - Disposal of domestic sludge and sludge ash on volcanic soils.
AB  - Column leaching experiments were conducted to test the ability of Chilean
      volcanic soils in retaining the mineral constituents and metals in sewage sludge
      and sludge ash that were incorporated into the soils. Small or negligible amounts
      of the total content of Pb, Fe, Cr, Mn, Cd, and Zn (0 to <2%), and more
      significant amounts of mineral constituents such as Na (7-9%), Ca (7-13%), PO4 (4
      10%), and SO4 (39-46%) in the sludge and sludge ash were readily soluble. When
      they were incorporated on the surface layer of the soils and leached with 12 pore
      volumes of water over a 3 month period of time, less than 0.1% of the total
      amount of heavy metals and PO4 in the sludge and sludge ash were collected in the
      drainage water. Cation exchange selectivity, specific anion adsorption and
      solubility are the processes that cause the reduction of leaching. The volcanic
      soils were capable of retaining the mineral constituents, P, and metals in
      applied sewage sludge and sludge ash and gradually released them as nutrients for
      plant growth.

PMID- 16650528
TI  - Treatment of nitrophenols by cathode reduction and electro-Fenton methods.
AB  - This study deals with the degradation of various nitrophenols by cathode
      reduction and electro-Fenton methods. Phenols (Poh), 2-nitrophenol (2-NP), 3
      nitrophenol (3-NP), 4-nitrophenol (4-NP), and 2,4-dinitrophenol (2,4-DNP) are
      treated and different degradation sequences are obtained. The relationship
      between the structure and activities of nitrophenols is discussed. Using 4-NP as
      a model nitrophenol, the electrochemical behaviors on graphite cathode and Pt
      anode are analyzed by cyclic voltammetry. The contribution of different reactions
      to the degradation of 4-NP is investigated in divided cells. The degradation of 4
      NP is much faster in the cathode cell than in the anodic cell. In the cathode
      cell, the degradation of 4-NP is significantly enhanced by the introduction of
      aeration and Fe(2+). Ultraviolet-visible (UV-vis) spectra reveal different
      reaction pathways for the degradation in the anodic cell and cathode cell.
      Treatment of high concentration of 4-NP in the undivided cell shows that more
      than 98% removal of 4-NP and about 13% removal of total organic carbon (TOC) are
      obtained for both processes, while the subsequent biodegradability test shows
      that electro-Fenton can eliminate the toxicity and improve the biodegradability
      of 4-NP. Negligible quantity of nitrate and nitrite ions detected in both
      processes indicates that there is no direct release of -NO(2) and -NO groups from
      4-NP and its degradation intermediates. Intermediates such as hydroquinone and
      bezoquinone are detected by gas chromatography/mass spectrum (GC/MS). The
      degradation pathway of 4-NP in electro-Fenton process is proposed as the cathode
      reduction followed by hydroxyl oxidation.

PMID- 16650529
TI  - Permeation of a straight oil metalworking fluid through a disposable and a
      chemically protective nitrile glove.
AB  - The aim of the present study was to quantify the permeation parameters of a
      complex water-insoluble straight oil metalworking fluid (MWF) of low volatility
      through nitrile gloves. The permeation through a chemically protective and a
      disposable glove was investigated using the American Society for Testing and
      Materials (ASTM) F739-99a method with hexane as the collection medium. Analysis
      of collection side samples involved gas chromatography-mass spectrometry (GC-MS)
      and gravimetry. The detection breakthrough time for the chemically protective
      glove was >10 h. For the disposable glove, the detection breakthrough time was
      0.7+/-0.3 h, the lag time was 1.6+/-0.1 h, the diffusion coefficient was (3.7+/
      0.3)x10(-9) cm2/min, and the steady state permeation rate was 3.5+/-2.2
      microg/cm2/min. The disposable nitrile glove can be worn for about 30 min for
      incidental contact with straight oil MWFs without known carcinogens. The
      chemically protective nitrile glove should be worn otherwise. The chromatogram
      for the permeate differed from that of the original MWF, resulting from the
      faster permeation of lower molecular weight congeners. The combination of
      chromatography and gravimetry allowed quantifying the permeation parameters of
      complex water-insoluble non-volatile mixtures.

PMID- 16650530
TI  - Update on endoscopic tissue sampling devices.

PMID- 16650531
TI  - Endoscopic clip application devices.

PMID- 16650532
TI  - Endoscopic ultrasound probes.

PMID- 16650533
TI  - Esophageal dilation.

PMID- 16650534
TI  - Pharyngeal anesthesia during sedated EGDs: is "the spray" beneficial? A meta
      analysis and systematic review.
AB  - BACKGROUND: Pharyngeal anesthesia is widely used as an adjunct to sedation during
      upper endoscopy. Methemoglobinemia and anaphylactic reactions are rare but
      serious complications of topical anesthetic agents. Individual studies produce
      variable results about the effectiveness of pharyngeal anesthesia in improving
      patient tolerance. OBJECTIVE: A systematic review was performed to evaluate the
      effectiveness of pharyngeal anesthesia in improving patient tolerance and ease of
      endoscopy during sedated upper endoscopy. DESIGN: A MEDLINE search, an EMBASE
      search, and manual searches were performed to identify pertinent English language
      articles. Randomized controlled trials (RCT) comparing the efficacy of pharyngeal
      anesthesia to placebo or no treatment were identified. Duplicate data extraction
      about patient tolerance of the procedure and endoscopist assessment regarding the
      ease of endoscopy was performed. RESULTS: From a pool of 53 studies, 5 RCTs
      evaluated a total of 491 patients and provided interpretable data. Patients who
      rated their discomfort during the sedated procedure as none/minimal were more
      likely to have received pharyngeal anesthesia (odds ratio [OR] 1.88, 95%
      confidence interval [CI] 1.13-3.12). Endoscopists were more likely to rate the
      procedure as "not difficult" for patients who received pharyngeal anesthesia (OR
      2.60, 95% CI 1.63-4.17). LIMITATIONS: Lack of standardized outcome measurements
      and standardized sedation strategies led to heterogeneity in the patient
      tolerance portion of the meta-analysis. CONCLUSIONS: Pharyngeal anesthesia before
      upper endoscopy improves ease of endoscopy and also improves patient tolerance.

PMID- 16650535
TI  - Comparison of hemostatic efficacy for epinephrine injection alone and injection
      combined with hemoclip therapy in treating high-risk bleeding ulcers.
AB  - BACKGROUND: Rebleeding occurs in 10% to 30% of bleeding ulcer patients receiving
      endoscopic epinephrine injection therapy. It remains unclear whether addition of
      a secondary clip therapy following epinephrine injection may reduce the
      rebleeding rate of high-risk bleeding ulcers. OBJECTIVE: To compare the
      efficacies of epinephrine injection alone and epinephrine injection combined with
      hemoclip therapy in treating high-risk bleeding ulcers. DESIGN: Prospective
      randomized controlled trial. SETTING: A medical center in Taiwan. PATIENTS: One
      hundred five bleeding ulcer patients with active spurting, oozing, nonbleeding
      visible vessels or adherent clots in ulcer bases. INTERVENTIONS: Endoscopic
      combination therapy (n = 52) or diluted epinephrine injection alone (n = 53).
      MAIN OUTCOME MEASUREMENTS: Initial hemostasis rates and recurrent bleeding rates.
      RESULTS: Initial hemostasis was achieved in 51 patients treated with combination
      therapy and 49 patients with epinephrine injection therapy (98% vs 92%, P = .18).
      Bleeding recurred in 2 patients in the combination therapy group and 11 patients
      in the epinephrine injection group (3.8% vs 21%, P = .008). Among the patients
      with rebleeding, repeated combination therapy was more effective than repeated
      injection therapy in achieving permanent hemostasis (100% vs 33%, P = .02). No
      patient required an emergency operation in the combination therapy group.
      However, 5 patients in the epinephrine injection group underwent emergency
      surgery to arrest bleeding (0% vs 9%, P = .023). LIMITATIONS: Treatment outcome
      of endoscopic hemoclip therapy is related to the techniques of endoscopists.
      CONCLUSION: Endoscopic combination therapy is superior to epinephrine injection
      alone in the treatment of high-risk bleeding ulcers.

PMID- 16650536
TI  - Best endoscopic hemostasis for ulcer bleeding: is there such a treatment?

PMID- 16650537
TI  - Clinical outcomes of EMR for gastric tumors: historical pilot evaluation between
      endoscopic submucosal dissection and conventional mucosal resection.
AB  - BACKGROUND: EMR is currently a standard treatment for mucosal gastric tumors.
      Endoscopic submucosal dissection (ESD) has been developed for en bloc resection.
      OBJECTIVE: We evaluated the clinical outcomes of ESD compared with conventional
      EMR. DESIGN: Not applicable. SETTING: A historical control study was performed
      between EMR and ESD. PATIENTS: EMR of 245 gastric tumors was performed in 229
      patients. Lesions were divided into two groups. Conventional EMR was performed in
      group A from February 1999 to June 2001, and ESD was performed in group B from
      July 2001 to March 2004. Group B was divided into subgroups: subgroup B-1
      underwent ESD from July 2001 to March 2003 and subgroup B-2 from April 2003 to
      March 2004. INTERVENTIONS: All lesions were resected with conventional EMR or
      with ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, rate in completeness
      of resection, required time, remnant ratio, and complications were evaluated.
      RESULTS: With regard to lesions >10 mm in size, the en bloc resection rate and
      the rate in completeness of resection of group B was significantly higher than
      that of group A (p < 0.01). Although the required time was longer in group B than
      A (p < 0.01), it was shorter in subgroup B-2 compared with B-1 (p < 0.05) with
      lesions < or =10 mm in size. The remnant ratio and perforation rate were not
      different between groups. LIMITATIONS: Not applicable. CONCLUSIONS: The en bloc
      resection rate was better with ESD than with conventional EMR. The required time
      was longer in ESD, but this disadvantage might be improved with experience.

PMID- 16650538
TI  - Can endoscopic resection be applied for early stage ampulla of Vater cancer?
AB  - BACKGROUND: Although endoscopic resection can provide a wide tumor resection with
      a negative resection margin, it is not yet recommended as a curative therapy for
      ampulla of Vater cancer. METHODS: To investigate the microinvasion rate and the
      diagnostic accuracy of endoscopic biopsy to properly judge the safety of
      endoscopic resection for ampulla of Vater cancer. DESIGN: Single-center,
      retrospective study. SETTING: Academic medical center. PATIENTS: One hundred
      fifty-nine patients who were finally diagnosed with ampulla of Vater cancer after
      curative surgical resection. INTERVENTIONS: We surveyed the pathologic
      concordance rate of endoscopic biopsy and the surgical pathology. For the 36
      early stage (Tis or T1) cancers, we surveyed the presence of microlymphovascular
      invasion, gross appearance (intra-ampullary type, periampullary type, or mixed
      type), and pathologic subtype (intestinal type or pancreaticobiliary type). MAIN
      OUTCOME MEASUREMENTS: Presence of microinvasion in early staged ampulla of Vater
      cancer. RESULTS: Endoscopic biopsy failed to reveal malignancy in 15.9% of the
      126 cases. Microlymphovascular invasion was present in 17 cases (56.7%) of the 30
      T1 cancers but was absent in all cases of the 6 Tis cancers (P = .02). Neither
      the gross appearance (P = .51) nor the pathologic subtype (P = .28) could predict
      the microinvasion rate. LIMITATIONS: Single-center, retrospective study with
      small number of patients. CONCLUSIONS: Although endoscopic resection improves the
      low predictability of endoscopic biopsy, surgical resection should be performed
      for the T1 stage ampulla of Vater cancer because of the high lymphovascular
      invasion rate. On the other hand, the safety of endoscopic resection should be
      evaluated by a large-scale study on Tis cancers to consider the absence of
      microinvasion.

PMID- 16650539
TI  - Endoscopic resection of tumors of the ampulla of Vater: how far up and how deep
      down can we go?

PMID- 16650540
TI  - Placement of a metallic stent across the main duodenal papilla may predispose to
      cholangitis.
AB  - BACKGROUND: Cholangitis is a major complication after metallic stent placement to
      treat biliary obstruction, and it may impair quality of life. Whether
      transpapillary stent placement contributes cholangitis is still controversial.
      OBJECTIVES: The present study aimed to determine risk factors for acute
      cholangitis after metallic biliary stent placement. DESIGN: Retrospective cases
      series. PATIENTS: A total of 108 patients with malignant biliary obstruction were
      treated with metallic stents, resulting in 12 cases of cholangitis. MAIN OUTCOME
      MEASUREMENTS: A multiple logistic regression model was performed with clinical
      parameters, including stent placement across the main duodenal papilla. RESULTS:
      By multiple logistic regression model, age; lower location; and Wallstent,
      Ultraflex stent, and covered stent were negatively associated with cholangitis.
      Restenosis and placement across the main duodenal papilla were positively
      associated with the occurrence of cholangitis. Transpapillary stent placement was
      the most significant risk factor. In this logistic model, the area under a
      receiver operating characteristics curve was computed as 0.92: sensitivity, 0.92
      (95% confidential interval (CI), 0.62-1.00); specificity, 0.86 (95% CI, 0.78
      0.93); positive predictive value, 0.46 (95% CI, 0.26-0.67); and negative
      predictive value, 0.99 (95% CI, 0.94-1.00). CONCLUSIONS: Disruption of the
      sphincter mechanism by transpapillary placement may be the most important
      etiologic factor in the propensity for cholangitis after metallic stent placement
      for malignant biliary obstruction.

PMID- 16650541
TI  - Single-step EUS-guided transmural drainage of simple and complicated pancreatic
      pseudocysts.
AB  - BACKGROUND: Single-step EUS-guided transmural drainage of pseudocysts has been
      reported, but there are no published prospective studies on clinical outcomes.
      OBJECTIVE: To assess the safety and the efficacy of single-step EUS-guided
      placement of large endoprostheses to treat simple and complicated pseudocysts.
      DESIGN: Prospective cohort study. SETTING: Single tertiary referral center.
      PATIENTS: Consecutive patients referred for management of symptomatic chronic
      pancreatic pseudocysts >4 cm in size. INTERVENTIONS: Single-step EUS-guided
      transmural pseudocyst drainage performed with a linear-array echoendoscope for
      placement of 10F stents in adults and 7F stents in children. MAIN OUTCOME
      MEASURES: Complete or partial (>50% reduction) resolution of pseudocyst on follow
      up imaging, recurrence, clinical response, and procedure-related complications.
      Recurrence was defined as the reappearance of a pancreatic pseudocyst in the same
      location. RESULTS: There were 33 patients, with a mean age of 43 years. Median
      pseudocyst size was 8.5 cm (range, 4-20 cm). Fourteen patients (42%) had infected
      pseudocysts, 8 patients (24%) had gastric varices, and 16 patients (48%) had no
      visible endoscopic bulge. Stent placement was successful in 31 patients (94%).
      Twenty-seven patients (82%) had complete resolution of a pseudocyst; 4 patients
      (12%) had partial resolution, with symptom relief. There were 2 major
      complications and 3 minor complications. Recurrence of a pseudocyst was observed
      in only 1 patient over a median follow-up of 46 weeks. LIMITATIONS: No randomized
      treatment arm comparing this technique with conventional endoscopic drainage.
      CONCLUSIONS: Single-step EUS-guided transmural drainage with large endoprostheses
      is a safe and effective therapy for patients with simple and complicated
      pancreatic pseudocysts.

PMID- 16650542
TI  - Delayed pancreaticoduodenectomy for cancer patients with prior ERCP-placed,
      nonforeshortening, self-expanding metal stents: a positive outcome.
AB  - BACKGROUND: Self-expanding metal stents (SEMS) inserted for malignant biliary
      obstruction are felt to be contraindicated in patients with resectable disease.
      Anecdotally, we observed a number of "unresectable" patients eventually
      undergoing a "delayed" pancreaticoduodenectomy after additional surgical
      opinions. This has not been previously described in the literature. OBJECTIVE: To
      quantitate the frequency with which patients diagnosed with unresectable
      pancreaticobiliary malignancy (and hence undergoing SEMS placement) eventually
      undergo Whipple's resection, and to report on the outcomes in these patients.
      DESIGN AND SETTING: This retrospective, observational study was conducted at a
      single tertiary care medical center. PATIENTS AND INTERVENTIONS: One hundred
      consecutive patients who underwent non-foreshortening SEMS placement for presumed
      unresectable pancreaticobiliary malignancy were identified from our ERCP
      database. The clinical course and any subsequent operative interventions were
      reviewed. RESULTS: Despite apparent unresectability, 13 of 100 patients underwent
      delayed surgical exploration for an attempt at resection. Whipple's resection was
      successfully performed in 5 patients. No interference with the biliary
      anastomosis was noted. No unresectable patient required surgical biliary bypass
      because of the presence of the stent. No pre- or postoperative infections
      occurred. CONCLUSIONS: Non-foreshortening metal stents can be precisely
      positioned below the line of any potential surgical transection. The lower risk
      of preoperative metal stent occlusion, compared to plastic stents, minimizes the
      risk of postoperative infection. At surgery, unresectable patients do not require
      unnecessary biliary bypass if a properly positioned SEMS is in place. Properly
      placed non-foreshortening biliary metal stents are not a contraindication to
      delayed attempts at Whipple's resection and may be beneficial.

PMID- 16650543
TI  - A prospective control study of the safety and cellular yield of EUS-guided FNA or
      Trucut biopsy in patients taking aspirin, nonsteroidal anti-inflammatory drugs,
      or prophylactic low molecular weight heparin.
AB  - BACKGROUND: Although the ASGE recommends that high-risk endoscopic procedures can
      safely be performed on patients taking aspirin and other nonsteroidal anti
      inflammatory drugs (NSAIDs) in standard doses, there is a paucity of data on EUS
      FNA per se in this setting. OBJECTIVE: We studied the safety and cellular yield
      of EUS-FNA and/or Trucut biopsy (TCB) in patients taking aspirin, NSAIDS, or
      prophylactic low molecular weight heparins (LMWH). DESIGN: Prospective control
      study. PATIENTS: Consecutive patients undergoing EUS-FNA and/or TCB were
      recruited over an 18-month period. The usage of aspirin, NSAIDS, or LMWH were
      recorded and patients who were not taking these medications served as controls.
      MAIN OUTCOME MEASUREMENTS: The bleeding events (endosonographic findings of
      extraluminal bleeding, intraluminal bleeding requiring hemostatic procedures,
      hematemesis, or melena) and cellular yield were compared between patients and
      controls. RESULTS: Two hundred fourteen patients (8 had repeat procedures)
      underwent EUS-FNA and/or TCB on 241 lesions. Bleeding events occurred in none (0
      of 26), 33.3% (2 of 6), and 3.7% (7 of 190) of the patients in the
      aspirin/NSAIDS, LMWH, and control groups, respectively (p = 0.023). The mean
      numbers of FNA passes, applications of suction, bloody specimens, and cellular
      yield were not significantly different between patients who were or were not
      receiving medications. No significant difference in bleeding events was noted
      between the FNA and TCB groups. CONCLUSION: EUS-FNA or TCB is safe in patients
      taking aspirin or NSAIDS. Consideration should be given to stopping LMWH before
      the procedure. The cellular yield and blood contamination of the specimen from
      FNA are similar to those in controls.

PMID- 16650544
TI  - Preoperative colonoscopy after self-expandable metallic stent placement in
      patients with acute neoplastic colon obstruction.
AB  - BACKGROUND: In patients with colorectal cancer, a preoperative colonoscopy is
      recommended to exclude synchronous lesions. Unfortunately, between 7% and 29% of
      patients with colorectal cancer present with acute colonic obstruction, making
      complete colonoscopy impossible. OBJECTIVE: The aim of our study was to evaluate
      the feasibility of a preoperative colonoscopy after effective stent placement in
      patients with acute neoplastic obstruction. DESIGN: Single-center prospective
      study. SETTING: All examinations were carried out at a tertiary referral center
      with 24-hour emergency endoscopy service. PATIENTS: Fifty-seven patients with
      acute neoplastic colon obstruction. INTERVENTIONS: Patients who recovered from an
      acute colon obstruction by an effective stent placement and who had a resectable
      cancer underwent a preoperative colonoscopy. MAIN OUTCOME MEASUREMENTS: Patients
      with a resectable cancer, complete preoperative colonoscopies, and synchronous
      lesions rates. RESULTS: Self-expandable metallic stents (SEMS) were placed in 50
      of 57 patients (87.8%). Thirty-one of 50 patients had a resectable cancer (62%),
      and a complete preoperative colonoscopy was possible in 29 of 31 patients
      (93.4%). A synchronous cancer was detected in 3 patients (9.6%), changing the
      surgical plan. LIMITATIONS: Seven patients in whom the SEMS placement (12.2%) was
      unsuccessful underwent an urgent surgical intervention. Nineteen of 50 patients
      who had stent placement were not eligible for our study because of unresectable
      cancer. CONCLUSIONS: Our study indicates that it is feasible in a majority of
      patients to perform full preoperative colonoscopy after relief of acute colonic
      obstruction with SEMS before surgical resection.

PMID- 16650545
TI  - Malignant colorectal obstruction: looking for synchronous lesions with the scope
      through a metal stent...!

PMID- 16650546
TI  - Accuracy of high-resolution chromoendoscopy in prediction of histologic findings
      in diminutive lesions of the rectosigmoid.
AB  - BACKGROUND: The ability to differentiate adenomatous from nonadenomatous colonic
      polyps by using chromoendoscopy would obviate the need to remove hyperplastic
      lesions. The aim of this study was to define the accuracy of high-resolution
      chromoendoscopy for the determination of colonic polyp histology. METHODS: In 158
      patients, 273 polyps (<5 mm) in the rectosigmoid were estimated for their
      histology. The endoscopists, in two steps, predicted the histopathology of each
      lesion on the basis of its surface characteristics by using high-resolution
      colonoscope without any staining and after indigo carmine dye according to the
      Kudo classification. RESULTS: The resected polyps included 48 adenomatous and 225
      nonadenomatous polyps. When histologically confirmed hyperplastic polyps were
      compared with adenomatous polyps, the prediction of hyperplastic polyps based on
      endoscopic findings had a sensitivity of 93%, a specificity of 60%, and an
      overall accuracy of 81%. The corresponding sensitivity, specificity, and overall
      accuracy after indigo carmine dye were 94%, 64%, and 83%, respectively.
      CONCLUSIONS: The results suggest that the chromoendoscopy only marginally
      improves the determination between hyperplastic and adenomatous polyps when using
      high-resolution colonoscopes. The overall accuracy rate increased after dyeing,
      from 81% to 83%. The omission of histopathologic analysis cannot yet be achieved
      by chromoendoscopy.

PMID- 16650547
TI  - Practicality of high-resolution chromoendoscopy during routine screening
      colonoscopy.

PMID- 16650548
TI  - Balancing family and career: addressing the challenges facing dual-career
      couples.

PMID- 16650549
TI  - NOTES: Gathering momentum.

PMID- 16650550
TI  - The Optical Dilator: a clear, over-the-scope bougie with sequential dilating
      segments.
AB  - PURPOSE: The safety and efficacy of esophageal dilation is enhanced when direct
      visualization is possible, tactile sensation and feedback from resistance is
      maintained, and multiple dilations with a single passage of the dilating device
      is an option. The InScope Optical Dilator (InScope, a Division of Ethicon Endo
      Surgery, Inc, Cincinnati, Ohio) is a flexible, transparent bougie fitted over a
      standard endoscope, with 3 dilating segments allowing sequential dilation under
      direct visualization. We report our experience with this device in treating
      benign esophageal strictures. METHODS: Patients with solid food dysphagia due to
      peptic strictures or Schatzki's ring were studied by using a 27F or 29F
      endoscope. Based on stricture appearance and estimated luminal diameter, 1 of 3
      dilator sizes was chosen: IN0216 (14-, 15-, and 16-mm dilating segments), IN0218
      (16-, 17-, and 18-mm dilating segments), or IN0220 (18-, 19-, and 20-mm dilating
      segments). RESULTS: Twenty-six patients were dilated and included 17 peptic
      strictures and 9 Schatzki's rings. Before dilation, most patients reported
      difficulties with solids at every meal. Median improvement 3 weeks after dilation
      was rated by patients as "substantial relief." Patients rated the dilation
      experience as largely "not at all unpleasant" immediately after endoscopy and had
      no recollection at 3 weeks' follow-up. There were no complications. Endoscopists
      rated dilator use as typical of experience with other bougies, and visualization
      was rated as high. CONCLUSION: The Optical Dilator maintains the value of tactile
      sensation and the convenience of 3 dilating sizes for each passage of the
      instrument with the added benefit of direct visualization.

PMID- 16650551
TI  - Optical dilators: a potential advance in the treatment of patients with
      dysphagia?

PMID- 16650552
TI  - Use of modified multiband ligator facilitates circumferential EMR in Barrett's
      esophagus (with video).
AB  - BACKGROUND: Various techniques are available for EMR in the upper- and lower-GI
      tract. For early cancers of the esophagus, the "suck and cut" technique, which
      uses a transparent cap or variceal band ligator, is the most commonly practiced
      method. To facilitate multiple or circumferential EMR, a modified multiband
      variceal ligator (MBL) is introduced, which allows sequential banding and snare
      resection without the need to withdraw the endoscope. OBJECTIVE: To study the
      feasibility of modified MBL device in facilitating circumferential EMR of
      Barrett's esophagus (BE) that contains high-grade intraepithelial neoplasia
      (HGIN) and/or intramucosal cancer (IMC). DESIGN: To enable band delivery with a
      snare inserted in the therapeutic endoscope, the threading channel of the
      cranking device is enlarged from 2 to 3.2 mm. The 6-shooter MBL was used.
      PATIENTS: Ten consecutive patients (all men; median age, 62 years; range 43-82
      years) with BE were treated. IMC and HGIN were found in 8 and 2 patients,
      respectively. INTERVENTIONS: EMR was performed with pure coagulating current when
      using a 1.5 x 2.5-cm mini hexagonal polypectomy snare. No submucosal saline
      solution injection was performed before resection. RESULTS: In 5 of 10 patients
      with circumferential BE of 2 to 9 cm in length (median, 4 cm), complete
      circumferential EMR was performed in 1 session by using 3 to 18 bands (median,
      6). Four patients with 3- to 10-cm (median, 4 cm) long segment BE required 2 to 5
      sessions (median, 3) with a total of 5 to 42 bands (median, 12). Another patient
      with multifocal HGIN and/or IMC in 24 of a total of 49 specimens was finally
      recommended for surgery because of technical difficulties caused by mural
      thickening after 4 sessions. No serious procedure-related complications were
      observed, except for 2 minor bleedings, which were controlled endoscopically.
      Seven patients developed strictures after circumferential EMR. All patients
      except 1 were successfully managed by weekly bougienage after a median of 5
      sessions (range 3-11). Deep-wall tears developed in 1 patient during the fourth
      bougienage session, for which limited distal esophageal resection was performed
      with an uneventful outcome. CONCLUSIONS: The novel technique of MBL-EMR described
      here facilitated and simplified circumferential removal of BE that contained HGIN
      and/or IMC. However, the method is associated with a very high stricture rate if
      circumferential EMR is performed in a single session. Complete removal of BE
      should be achieved by repeated partial EMR. Long-term follow-up is needed to
      observe for late recurrence and to determine the clinical impact of this method.

PMID- 16650553
TI  - Endoscopic direct cholangioscopy by using an ultra-slim upper endoscope: a
      feasibility study.
AB  - BACKGROUND: The search for an easier and less cumbersome technique to perform
      direct visual examination of the biliary tree is still underway. OBJECTIVE: To
      assess the feasibility of performing endoscopic direct cholangioscopy utilizing
      an ultra-slim upper endoscope designed for pediatric patients. DESIGN:
      Prospective, observational, pilot study. SETTING: Tertiary referral center.
      PATIENTS: Three patients who underwent endoscopic retrograde cholangiography for
      evaluation and treatment of choledocholithiasis. METHODS: Following the
      completion of the endoscopic retrograde cholangiography, a 0.035-inch diameter
      super-stiff Jagwire (Boston Scientific Corp, Natick, Mass) was placed in the
      common bile duct. Using the wire to maintain access, we removed the duodenoscope
      and backloaded the wire onto an ultra-slim upper endoscope (GIF-XP 160, Olympus
      America Inc, Melville, NY), which was advanced over the guidewire under
      fluoroscopic and endoscopic control into the duodenum and then across the ampulla
      of Vater into the common bile duct and upstream. RESULTS: Endoscopic direct
      cholangioscopy was attempted and successfully completed in all 3 patients. One
      patient was found to have persistent large amount of sludge and stones, and was
      referred for surgery. In the other two patients, endoscopic direct cholangioscopy
      demonstrated complete duct clearance, obviating the need for stent placement and
      repeat endoscopic retrograde cholangiography procedures. LIMITATIONS: Small
      sample size, pilot study. CONCLUSIONS: Endoscopic direct cholangioscopy with an
      ultra-slim upper endoscope originally designed for pediatric use is feasible.
      Future advances in endoscope development, as well as specifically designed
      accessories, could lead to the next generation of intraductal diagnosis and
      therapy.

PMID- 16650554
TI  - Paleoscopy.

PMID- 16650555
TI  - Recurrent malignant thymoma diagnosed by EUS-guided Trucut biopsy.

PMID- 16650556
TI  - Gastric piercing.

PMID- 16650557
TI  - Bile duct cancer in the setting of intraductal papillary mucinous tumor appearing
      as an impacted bile duct stone on ERCP.

PMID- 16650558
TI  - Angiodysplasia of the major duodenal papilla: a rare cause of GI bleeding.

PMID- 16650559
TI  - Jejunal diverticulosis diagnosed by double-balloon enteroscopy.

PMID- 16650560
TI  - Use of endoclips to obliterate a colonic arteriovenous malformation before
      cauterization.

PMID- 16650561
TI  - Colon varices as a source for lower-GI bleeding.

PMID- 16650562
TI  - Polyarteritis nodosa presenting as massive upper gastrointestinal hemorrhage.

PMID- 16650563
TI  - Concurrent mucinous cystadenoma of the liver and bile duct: a rare cause of
      jaundice.

PMID- 16650564
TI  - Metastatic melanoma of the common bile duct and ampulla of Vater.

PMID- 16650565
TI  - Biliary stent migration presenting as a recurrent abdominal wall abscess with
      underlying enterocutaneous fistula.

PMID- 16650566
TI  - Massive pneumoperitoneum after EUS-FNA aspiration of the pancreas.

PMID- 16650567
TI  - Successful laparoscopic treatment of hemorrhage from the appendix with
      phlegmonous acute appendicitis: a case report and review of the literature.

PMID- 16650568
TI  - Colonic varices treated by balloon-occluded retrograde transvenous obliteration
      in a cirrhotic patient with encephalopathy: a case report.

PMID- 16650569
TI  - Potential cancer cell inoculation of tattoo site through use of a contaminated
      needle.

PMID- 16650570
TI  - Melanosis of the colon and terminal ileum associated with primary malignant
      melanoma of the anorectum.

PMID- 16650571
TI  - Acute upper-GI bleeding does not decrease the diagnostic yield of gastric
      biopsies for Helicobacter pylori infection.

PMID- 16650572
TI  - Endotherapy for distally migrated metallic biliary endoprostheses.

PMID- 16650573
TI  - Antibiotics are mandatory before EUS-guided FNA in cystic or semisolid lesions of
      the mediastinum and the pancreas.

PMID- 16650574
TI  - Colonoscopic resection of an asymptomatic colon lipoma.

PMID- 16650576
TI  - A TAT-modified fusion protein efficiently penetrates mouse hypoglossal nuclei
      from transduced ependyma.
AB  - Future gene therapy for brainstem variant amyotrophic lateral sclerosis may be
      technically difficult if gene therapy vectors are injected near vital
      cardiorespiratory centers or if large portions of the tongue and pharyngeal
      muscles must be peripherally injected for retrograde transport of vectors to
      motor neurons. In this study we show that it is possible to deliver recombinant
      proteins to the hypoglossal nuclei without brainstem or muscle injections, by
      taking advantage of enhanced uptake of fusion proteins containing the protein
      transduction domain from the human immunodeficiency virus TAT protein. Adenoviral
      vectors expressing either TAT-modified or native beta-glucuronidase (beta-gluc)
      were injected into the lateral cerebral ventricles of mice, transducing
      ventricular epithelium down to the level of the obex in the brainstem. There was
      significant uptake into the hypoglossal nuclei of TAT-modified but not native
      beta-glucuronidase. The TAT-modified beta-gluc appeared to encompass half or more
      of the hypoglossal nuclei as visualized by retrograde labeling with cholera toxin
      subunit b in adjacent sections. TAT-modification of gene products may allow a
      relatively non-invasive approach to brainstem gene therapy via cerebroventricular
      injection.

PMID- 16650577
TI  - Study of anticonvulsant effect of citronellol, a monoterpene alcohol, in rodents.
AB  - Citronellol is one monoterpene alcohol, which is present in the essential oils of
      various aromatic plant species. This study evaluated the neuroprotective activity
      of citronellol on pentylenetetrazol- and picrotoxin-induced convulsions and
      maximal electroshock-induced seizures in mice. Administration of citronellol
      significantly reduced the number of animals of convulsion induced by
      pentylenetetrazol and eliminated the extensor reflex of maximal electroshock
      induced seizures test in about 80% of the experimental animals. In addition,
      administration of citronellol showed protection in the pentylenetetrazol and
      picrotoxin tests by increasing the latency of clonic seizures. We also
      investigated the effect of citronellol in the rat isolated nerve using the single
      sucrose-gap technique. We showed that the amplitude of the compound action
      potential decreased more than 90% when the monoterpene was incubated for 30 min
      at 6.4 mM and we did not verify any effect on the repolarization of the compound
      action potential. Taken together, our results demonstrated an anticonvulsant
      activity of the citronellol that could be, at least in part, explained by the
      diminution of the action potential amplitude.

PMID- 16650578
TI  - Alpha2-macroglobulin, lipoprotein receptor-related protein and lipoprotein
      receptor-associated protein and the genetic risk for developing Alzheimer's
      disease.
AB  - Alpha2-macroglobulin (alpha2M) as well as its receptor, the low-density
      lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are
      involved in the clearance of cerebral A beta. Current evidence suggests that
      polymorphisms in the genes of alpha2M, LRP and RAP may have functional effects on
      the proteins. Two independent association samples of 271 AD patients and 280
      representative controls were investigated whether the risk for developing AD is
      altered in carriers of polymorphisms in the alpha2M-gene (Va1000Ile), in the LRP
      gene (Ala216Val) and in the RAP-gene (Val311Met). Genotypes were determined by
      standard PCR and restriction fragment length polymorphism. The results were
      adjusted for age, gender and apolipoprotein E-epsilon4 (APOE) polymorphism.
      Inheritance of alpha2M conferred a small increased risk for sporadic AD with an
      estimated Mantel-Haenszel odds ratio of 1.47. There was no age- or gender
      dependent increase in alpha2M Val1000Ile allele frequencies in AD patients
      compared to controls. There was no significant difference in the allele
      frequencies among control and AD subjects for the LRP and RAP polymorphisms. We
      found no evidence of an interaction between the alpha2M and RAP or LRP with
      regard to conferred risk. Our data suggest that the alpha2M Val1000Ile
      polymorphism is weakly associated with AD. Although LRP as well as RAP seem to
      play an essential role in the metabolism of alpha2M and APOE, there is no
      increase in the genetic risk for AD in patients carrying the investigated
      polymorphisms.

PMID- 16650579
TI  - Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: in
      vitro and in vivo studies in rat.
AB  - Several lines of evidence support an important role for somatostatin receptors
      (SSTRs) in pain modulation. The therapeutic use of established SSTR peptide
      agonists for this indication is limited by their broad range of effects, need for
      intrathecal delivery, and short half-life. Therefore, the goal of the present
      study was to investigate the analgesic effect of SCR007, a new, highly selective
      SSTR2 non-peptide agonist. Behavioral studies demonstrated that paw withdrawal
      latencies to heat were significantly increased following intraplantar SCR007.
      Furthermore, both intraperitoneal and intraplantar injection of SCR007
      significantly reduced formalin- and capsaicin-induced flinching and
      lifting/licking nociceptive behaviors. Recordings from nociceptors using an in
      vitro glabrous skin-nerve preparation showed that SCR007 reduced heat responses
      in a dose-dependent fashion, bradykinin-induced excitation, heat sensitization
      and capsaicin-induced excitation. In both the behavioral and single fiber
      studies, the SCR007 effects were reversed by the SSTR antagonist cyclo
      somatostatin, demonstrating receptor specificity. In the single fiber studies,
      the opioid antagonist naloxone did not reverse SCR007-induced anti-nociception
      suggesting that SCR007 did not exert its effects through activation of opioid
      receptors. Analysis of cAMP/protein kinase A (PKA) involvement demonstrated that
      SCR007 prevented forskolin- and Sp-8-Br-cAMPS (a PKA activator)-induced heat
      sensitization, supporting the hypothesis that SCR007-induced inhibition could
      involve a down-regulation of the cAMP/PKA pathway. These data provide several
      lines of evidence that the non-peptide imidazolidinedione SSTR2 agonist SCR007 is
      a promising anti-nociceptive and analgesic agent for the treatment of pain of
      peripheral and/or central origin.

PMID- 16650580
TI  - Chronic pain and sensory changes after augmentation mammoplasty: long term
      effects of preincisional administration of methylprednisolone.
AB  - We studied the prevalence of chronic pain and long term sensory changes after
      cosmetic augmentation mammoplasty and the effects of a single i.v. preoperative
      dose of methylprednisolone 125 mg (n=74), parecoxib 40 mg (n=71), or placebo
      (n=74). A questionnaire was mailed 6 weeks and 1 year after surgery. Response
      rate after 1 year was 80%. At 1 year non-evoked pain was present in 13%, and
      evoked pain was present in 20% with no statistically significant differences
      between the groups. Methylprednisolone was associated with reduced odds for
      hyperesthesia at 1 year (OR 0.3, 95% CI 0.1-0.6), and significantly reduced the
      prevalence of hyperesthesia (30%) compared with placebo (56%, P<0.01) and
      parecoxib (51%, P<0.04). Factors associated with increased odds for pain at 1
      year were intensity of pain during the first 6 days after surgery (OR 1.3, 95% CI
      1.1-1.6), pain at 6 weeks (OR 18.4, 95% CI 6.9-49.3), hyperesthesia at 6 weeks
      (OR 2.3, 95% CI 1.1-5.1) and present hyperesthesia (OR 3.1, 95% CI 1.4-6.7). We
      conclude that persistent pain and sensory changes are common after augmentation
      mammoplasty, and that patients having pain at 6 weeks most likely will have pain
      also at 1 year. Acute postoperative pain, hyperesthesia at 6 weeks, and the
      presence of hyperesthesia increased the odds for pain at 1 year. Preoperative
      methylprednisolone resulted in significantly less hyperesthesia compared with
      both parecoxib and placebo, but did not significantly reduce the prevalence of
      persistent spontaneous or evoked pain.

PMID- 16650581
TI  - Midbrain control of spinal nociception discriminates between responses evoked by
      myelinated and unmyelinated heat nociceptors in the rat.
AB  - Descending control of spinal nociception is a major determinant of normal and
      chronic pain. Myelinated (A-fibre) and unmyelinated (C-fibre) nociceptors convey
      different qualities of the pain signal (first and second pain, respectively), and
      they play different roles in the development and maintenance of chronic pain
      states. It is of considerable importance, therefore, to determine whether
      descending control has differential effects on the central processing of A- vs. C
      nociceptive input. In anaesthetised rats, biceps femoris EMG was recorded to
      monitor the thresholds and encoding properties of responses evoked by fast (7.5
      degrees Cs(-1)) or slow (2.5 degrees Cs(-1)) rates of skin heating of the dorsal
      surface of a hindpaw to preferentially activate myelinated or unmyelinated heat
      nociceptors, respectively. Activation of neurones in the periaqueductal grey
      (PAG) by microinjection of dl-homocysteic acid (DLH) or bicuculline (BIC)
      significantly increased response thresholds to slow rates of heating (P<0.001),
      but not those to fast rates of heating (P>0.05). The ability of the EMG to encode
      the stimulus intensity of fast rates of skin heating remained intact and
      unaltered (r2=0.99, P<0.001) following BIC but not DLH injection. In contrast,
      encoding of the stimulus intensity of slow rates of skin heating was abolished
      following BIC and DLH injection. The functional significance of differential
      descending control of the central processing of C- and A-nociceptive inputs is
      discussed with respect to role of the PAG in mediating antinociception as part of
      active coping strategies in emergency situations and the role of C- and A
      nociceptive inputs in animal models of chronic pain.

PMID- 16650582
TI  - Signaling pathway of morphine induced acute thermal hyperalgesia in mice.
AB  - Systemic administration of morphine induced a hyperalgesic response in the hot
      plate test, at an extremely low dose (1-10 microg/kg). We have examined in vivo
      whether morphine, at an extremely low dose, induces acute central
      hypernociception following activation of the opioid receptor-mediated PLC/PKC
      inositol-lipid signaling pathway. The PLC inhibitor U73122 and the PKC blocker,
      calphostin C, dose dependently prevented the thermal hypernociception induced by
      morphine. This effect was also prevented by pretreatment with aODN against
      PLCbeta3 at 2 nmol/mouse and PKCgamma at 2-3 nmol/mouse. Low dose morphine
      hyperalgesia was dose dependently reversed by selective NMDA antagonist MK801 and
      ketamine. This study demonstrates the presence of a nociceptive
      PLCbeta3/PKCgamma/NMDA pathway stimulated by low concentrations of morphine,
      through muOR1 receptor, in mouse brain. This signaling pathway appears to play an
      opposing role in morphine analgesia. When mice were treated with a morphine
      analgesic dose (7 mg/kg), the downregulation of PLCbeta3 or PKCgamma at the same
      aODN doses used for the prevention of the hyperalgesic effect induced,
      respectively, a 46% and 67% potentiation in analgesic response. Experimental and
      clinical studies suggest that opioid may activate pronociceptive systems, leading
      to pain hypersensitivity and short-term tolerance, a phenomenon encountered in
      postoperative pain management by acute opioid administration. The clinical
      management of pain by morphine may be revisited in light of the identification of
      the signaling molecules of the hyperalgesic pathway.

PMID- 16650583
TI  - Effect of autogenic training on cardiac autonomic nervous activity in high-risk
      fire service workers for posttraumatic stress disorder.
AB  - OBJECTIVE: We investigated the effect of autogenic training (AT) on cardiac
      autonomic nervous activity in fire services workers with the use of the
      questionnaire of the Japanese-language version of Impact of Event Scale-Revised
      (IES-R-J) and indexes of heart rate variability. METHODS: We studied 22 male fire
      services workers who were divided into posttraumatic stress disorder (PTSD)
      related stress group (n=10) and control group (n=12). They underwent AT twice or
      three times a week for 2 months. RESULTS: Posttraumatic stress disorder-related
      stress group showed a significantly higher cardiac sympathetic nervous activity
      and a significantly lower cardiac parasympathetic nervous activity than control
      group at baseline. Autogenic training significantly decreased cardiac sympathetic
      nervous activity and significantly increased cardiac parasympathetic nervous
      activity in both groups. These changes were accompanied by a significant decrease
      in the total points of IES-R-J. CONCLUSION: Autogenic training is effective for
      ameliorating the disturbance of cardiac autonomic nervous activity and
      psychological issues secondary to PTSD.

PMID- 16650584
TI  - Anxiety and depression in primary care patients: predictors of symptom severity
      and developmental correlates.
AB  - OBJECTIVE: A study in a German general practice used the Hospital Anxiety and
      Depression Scale (HADS) to determine the prevalence of anxiety and depression in
      242 consecutive patients. The study had two additional goals: (1) to identify
      indicators of symptom severity and (2) to validate the HADS by relating it to
      measures of developmental psychopathology. METHODS: In addition to the HADS,
      clinical/sociodemographic data were collected. Patients filled up additional
      questionnaires measuring attachment characteristics, recalled parental rearing
      behavior, resilience, adverse childhood experiences, and physical complaints.
      RESULTS: Using HADS cutoff scores of > or =11 in total, we found that 21.1% of
      the patients showed clinically relevant anxiety levels; the rate for depression
      was 12.0%, that for anxiety or depression was 26.1%, and that for anxiety and
      depression combined was 7%. With the exception of psychiatric disorders, the HADS
      did not differentiate between subgroups with different somatic diseases. HADS
      scores were shown to be predicted by the patients' sex, family status, number of
      consultations, and subjective physical complaints. Patients with higher HADS
      scores also indicated lower resilience, more insecure attachment, and negative
      recalled parental rearing behavior. Resilience, attachment security, and specific
      parental behavior (control/warmth) independently predicted anxiety, depression,
      and physical complaints. CONCLUSION: This study provides further support for the
      usefulness of the HADS as a measure for routine screening for anxiety and
      depression and its relationship with constructs from developmental
      psychopathology. We recommend the use of the HADS in combination with potential
      indicators of symptom severity (fatigue, cardiovascular symptoms, high number of
      consultations) to identify patients needing psychosocial support.

PMID- 16650585
TI  - Major depressive disorders in the general hospital: how to implement guidelines.
AB  - OBJECTIVE: An implementation study that evaluated the impact of previously
      adopted guidelines on the clinical practice of medical residents was conducted to
      improve the recognition and treatment of major depressive disorders (MDDs) in
      hospitalized patients with somatic diseases. METHODS: Guidelines were implemented
      in two wards (ENT and oncology) using intranet diffusion, interactive sessions
      with medical residents, and support material. Discharge letters of 337 and 325
      patients, before and after the intervention, respectively, were checked for
      statement of diagnosis or treatment of MDDs and, in a post hoc analysis, for any
      mention about psychiatric management. RESULTS: No difference was found in the
      number of diagnosed or treated MDDs before and after the intervention. However,
      significantly more statements about psychological status (29/309 vs. 13/327) and
      its management (36/309 vs. 19/327) were observed after the intervention (P<.01).
      CONCLUSION: The intervention was not successful in improving the management of
      MDDs. However, a possible effect on general psychological aspects of medical
      diseases was observed.

PMID- 16650586
TI  - The Hospital Anxiety and Depression Scale depression subscale, but not the Beck
      Depression Inventory-Fast Scale, identifies patients with acute coronary syndrome
      at elevated risk of 1-year mortality.
AB  - OBJECTIVE: The objective of this study was to investigate the use of short-form
      depression scales in assessing 1-year mortality risk in a national sample of
      patients with acute coronary syndrome (ACS). METHODS: Patients with ACS (N=598)
      completed either the Hospital Anxiety and Depression Scale depression subscale
      (HADS-D) or the Beck Depression Inventory-Fast Scale (BDI-FS). Their mortality
      status was assessed at 1 year. RESULTS: Cox proportional hazards modeling showed
      that patients depressed at baseline (combining HADS-D and BDI-FS depressed cases)
      were more likely to die within 1 year [hazard ratio (HR)=2.8, 95% CI=1.4-5.7,
      P=.005], even when controlling for major medical and demographic variables
      (HR=4.1, 95% CI=1.6-10.3, P=.003). Scoring above the threshold on the HADS-D
      predicted mortality (HR=4.2, 95% CI=1.8-10.0, P=.001), but scoring above the
      threshold on the BDI-FS did not (HR=1.8, 95% CI=0.6-5.6, P=.291). CONCLUSION: The
      HADS-D predicted increased risk of 1-year mortality in patients with ACS.

PMID- 16650587
TI  - Depression in rheumatoid arthritis patients: demographic, clinical, and
      psychological predictors.
AB  - OBJECTIVE: To confirm the prevalence of depression in a sample of rheumatoid
      arthritis (RA) patients; to identify the most significant predictors of
      depression in RA and to explore patients attitudes to medication in relation to
      depression. METHODS: A cross-sectional survey was used to collect data from 134
      RA patients (77% female, 23% male). Participants were divided into depressed and
      nondepressed groups based on their scores on the Center for Epidemiological
      Studies-Depression (CES-D) scale. Discriminant analysis was conducted to identify
      the predictors that would best categorise patients into those two groups.
      RESULTS: Twelve predictors correctly classified 80% of patients into depressed or
      nondepressed groups. The strongest predictors of depression were high tension and
      low self-esteem followed by the perceived impact of RA, fatigue, passive coping,
      pain, and physical disability. Other predictors included medication effectiveness
      and importance as well as perceived lack of control over pain. CONCLUSION: Both
      physical and psychological factors have an impact on depression in RA. The key
      predictors identified in this study need to be considered within the regular RA
      management as possible cues to depression development.

PMID- 16650588
TI  - Positive affect as a factor of resilience in the pain-negative affect
      relationship in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a
      factor of resilience in the relationships between pain and negative affect (NA)
      in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients
      (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks.
      Multilevel modeling was applied to study the within-week relationships among the
      variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05,
      P<.01) indicating a weaker relationship between pain and NA in weeks with more
      PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001),
      depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and
      also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive
      affect is most influential in reducing NA during weeks of higher pain and may be
      a factor of resilience, helping patients experiencing pain fluctuations as less
      distressful than at lower levels of PA.

PMID- 16650589
TI  - Psychometric evaluation of the Ways of Coping Questionnaire as applied to
      clinical and nonclinical groups.
AB  - OBJECTIVE: The purpose of this study is to describe coping and evaluate the
      psychometric properties and the factor structure of the Ways of Coping
      Questionnaire (WCQ) applied to clinical and nonclinical groups. METHOD: The
      responses of 510 subjects (chronically disabled patients, their next of kin, and
      students) who completed the Swedish version of the WCQ were the basis for
      confirmatory factor analyses of the original eight-factor model as well as of the
      model consistency across samples. RESULTS: The coping patterns that emerged in
      the case of the patients were very similar to those of the next of kin. The
      exceptions were greater use of Distancing by patients and of Positive Reappraisal
      by next of kin. The results showed support for the original eight-factor model,
      but deviation from the equality of factor structures among the subsamples
      indicated a limited use of the WCQ in between-sample comparisons. CONCLUSION:
      Modifications to the eight-factor model adequately described the subsamples,
      supporting the use of the WCQ in within-sample settings. This was particularly
      evident from the evaluation of alternative factor structures based on previously
      described models derived from clinical samples.

PMID- 16650590
TI  - Validation of the Kidney Disease Quality of Life-Short Form questionnaire in
      kidney transplant patients.
AB  - OBJECTIVE: The aim of this study was to determine the basic psychometric
      properties, reliability, and validity of the Kidney Disease Quality of Life-Short
      Form (KDQOL-SF) questionnaire in kidney transplant patients. METHODS: The
      reliability and validity of the instrument were determined in 418 kidney
      transplant patients followed in a single outpatient transplant centre. RESULTS:
      Internal consistency of all the Medical Outcome Study Short Form 36 (SF-36)
      domains was very good, and the Cronbach's alpha value was above .70 for all but
      three of the disease-specific subscales. We found significant, moderate to strong
      negative correlations between most of the KDQOL-SF domains and the Center for
      Epidemiologic Studies-Depression (CES-D) scores. Finally, substantial differences
      in KDQOL-SF scores were seen between groups of transplanted patients who were
      expected to be clinically different, supporting the discriminant validity of the
      KDQOL-SF instrument. CONCLUSION: We propose that the KDQOL-SF is a reliable and
      valid tool and most of its subscales can be used to assess health-related quality
      of life (HRQOL) in kidney transplant patients and to compare HRQOL between
      different end stage renal disease (ESRD) patient populations.

PMID- 16650591
TI  - Psychosocial adaptation and quality of life among Brazilian patients with
      different hematological malignancies.
AB  - This study aims to investigate the prevalence of posttraumatic stress disorder
      (PTSD) symptoms, anxiety, and depression in patients with hematological
      malignancies, and to investigate the possible relationship between these symptoms
      and variables such as demographic data, social support, and quality of life
      (QOL). We studied 107 patients: 54 with non-Hodgkin's lymphoma (NHL), 18 acute
      myelogenous leukaemia (AML), 10 acute lymphoblastic leukaemia (ALL), and 25
      multiple myeloma (MM). Demographic data were collected, and three standardized
      instruments were applied to this group of patients: Hospital Anxiety and
      Depression Scale (HADS), Impact of Event Scale (IES), European Organization for
      Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire of QOL. The
      results showed a significant percentage of patients presenting with symptoms: 13%
      had high levels of intrusive thoughts, 20.5% had high levels of anxiety, and
      16.8% had high levels of depression. Patients with MM had the lowest QOL scores
      in the EORTC physical functioning subscale. Patients under intravenous
      chemotherapy treatment had a higher level of anxiety than the monitoring
      patients. Patients with recent diagnosis had a level of intrusion symptoms (IES)
      relevantly higher than the others. The unemployed patients and those with lower
      social support had levels of stress, anxiety, and depression significantly higher
      than the others. Our results confirm the high incidence of intrusion, avoidance,
      anxiety, and depression in patients with hematological malignancies and highlight
      the importance of a multidisciplinary staff to complement the treatment of these
      patients, including psychosocial assistance.

PMID- 16650592
TI  - Quality of life and psychological status in survivors of severe acute respiratory
      syndrome at 3 months postdischarge.
AB  - BACKGROUND: Little is known about the long-term consequence of severe acute
      respiratory syndrome (SARS). We carried out an assessment on SARS patients after
      their recovery from their acute illness. METHOD: Postal survey comprising Health
      Related Quality of Life (HRQoL) questionnaires and anxiety and depression
      measures was sent to them at 3 months' postdischarge. RESULTS: There was a
      significant impairment in both the HRQoL and mental functioning. Forty-one
      percent had scores indicative of a posttraumatic stress disorder (PTSD); about
      30% had likely anxiety and depression. CONCLUSION: SARS has significant impact on
      HRQoL and psychological status at 3 months.

PMID- 16650593
TI  - Emotional reactivity and the overreport of somatic symptoms: somatic sensitivity
      or negative reporting style?
AB  - OBJECTIVE: The purpose of this study is to examine the role of emotional
      reactivity (ER) in symptom reporting and conceptualize somatizing processes as a
      signal detection task. Emotional reactivity has been theorized to influence
      symptom reporting through somatic sensitivity as well as via a negative reporting
      style. We assess the degree to which these two competing theories about the role
      of ER are accurate within the signal detection framework. METHODS: We used a
      multimethod approach that included using both static and prospective self-reports
      as well as a signal detection task. RESULTS: Results suggest that ER exerts its
      influence on somatization tendencies via a negatively biased reporting style and
      is not mediated by somatic sensitivity as suggested by the somatosensory
      amplification and the symptom perception hypothesis. CONCLUSION: Emotional
      reactivity has yet to be associated with objective measures of somatic
      sensitivity. Until such an association is found, it is likely that ER influences
      symptom reports via negatively biased reporting.

PMID- 16650594
TI  - Prevalence of tattooing and body piercing in Germany and perception of health,
      mental disorders, and sensation seeking among tattooed and body-pierced
      individuals.
AB  - OBJECTIVE: The objective of this study was to obtain data on the incidence and
      relationship of psychological factors to tattooing and body piercing from a large
      and representative sample of German citizens (N=2043). METHODOLOGY:
      Representative data (sample age range=14-93 years) were evaluated with respect to
      health-related quality of life (SF-36), mental health (General Health
      Questionnaire), mental disorders (Patient Health Questionnaire), and sensation
      seeking (Arnett Inventory of Sensation Seeking). RESULTS: The prevalence of
      tattooing and that of body piercing in the general German population are 8.5% and
      6.5%, respectively. Individuals aged between 14 and 24 years display the highest
      rate of body piercings or tattoos (females, 41%; males, 27%). Within the group of
      individuals aged between 14 and 44 years, unemployment and nonaffiliation to a
      church are positively correlated, tattooing is significantly correlated with the
      perception of reduced mental health, and both tattooing and body piercing are
      correlated with significantly increased sensation-seeking behavior. CONCLUSIONS:
      Next to being motivated by fashion and the urge to fit in with one's peers, the
      major reasons for body modification practices in the German population appear to
      be negatively perceived conditions of life, reduced social integration, and
      increased sensation-seeking behavior.

PMID- 16650595
TI  - A new conceptualization of alexithymia in the general adult population:
      implications for research involving older adults.
AB  - OBJECTIVE: The purpose of this study is to test the validity of existing
      conceptualizations of the alexithymia concept, with particular reference to
      aging. METHODS: Two hundred and forty-eight healthy adults completed measures of
      alexithymia and psychosocial functioning; younger and older adults (n=121) also
      completed a measure of emotional responsiveness. RESULTS: Older adults engaged in
      less introspective thought traditionally thought to denote increased alexithymia.
      However, reduced introspection was associated with improved mental wellbeing,
      and, thus, could not be construed as a deficit. Difficulty identifying and
      describing emotions did not differentiate older and younger adults, but were both
      associated with heightened depression, anxiety, and poor perceived quality of
      life. CONCLUSIONS: In clinical practice and research, the Toronto Alexithymia
      Scale (TAS) is almost exclusively used, with "total" score typically used to
      index alexithymia. As one of the subscales of the TAS measures reduced
      introspection, calculating total scores may not be appropriate and may
      particularly overestimate levels of alexithymia in older adulthood.

PMID- 16650596
TI  - Kissing selectively decreases allergen-specific IgE production in atopic
      patients.
AB  - OBJECTIVE: Stress enhanced allergic skin wheal responses and allergen-specific
      IgE production. In contrast, mothers' kissing caused relaxation in infants, and
      kissing by lovers or spouses to atopic patients reduced allergic skin wheal
      responses. I studied the effect of kissing on production of allergen-specific IgE
      and cytokines in atopic patients. METHODS: Twenty-four patients with mild atopic
      eczema and 24 patients with mild allergic rhinitis kissed with lovers or spouses
      freely for 30 min while listening to soft music. Just before and immediately
      after kissing, blood mononuclear cells were separated cultured for allergen, and
      production of allergen-specific immunoglobulin and cytokine was measured.
      RESULTS: Kissing selectively decreased allergen-specific IgE production with
      skewing cytokine pattern toward Th1 type. CONCLUSION: Kissing may alleviate
      allergic symptoms by decrease in allergen-specific IgE production.

PMID- 16650597
TI  - Contracaecum sp. infection in Hoplias malabaricus (moncholo) from rivers and
      marshes of Colombia.
AB  - Nematode infection indices were recorded in Hoplias malabaricus captured in six
      different rivers and a marsh belonging to the North Coast Basin of Colombia, and
      from the Amazon River, during February 2003-December 2004. Preliminary
      morphological analysis of nematodes indicated the presence of Contracaecum sp.
      Parasites were mostly found in the intestinal mesenteries and a very low
      percentage in muscle. Parasite prevalence in all sampling locations at the north
      of Colombia was 100%, whereas in the Amazon River it was 6.12%. The mean
      intensity in the different stations were as follows: Magdalena River at the City
      of Magangue (58.92+/-7.59), Magdalena river at the city of Zambrano (128.9+/
      7.08), Sinu River (53.88+/-4.92), Dique Channel (207.3+/-59.52), Cauca River
      (77.26+/-9.35), Atrato River (21.11+/-2.6), San Jorge River (39.5+/-7.13), and
      Totumo Marsh (62.5+/-6.38). In average, all specimens of Hoplias malabaricus from
      the north coast basin of Colombia were infected with a mean intensity of 77.82+/
      4.81 (1-466 parasites per host) whereas in fish from the Amazon River this value
      was significantly lower (intensity 1.0+/-0.0). Size and weight correlated
      significantly with parasite intensity in fish collected from sampling locations
      at the north of Colombia (R=0.240, P<0.001 and R=0.199, P=0.008, respectively).
      Moreover, a significant, but low and negative correlation was found between
      condition factor and parasite intensity (R=-0.159, P=0.034), suggesting a
      possible impact of parasites on fish health. These results suggest, for the first
      time, that the parasitism in Moncholo is a widespread phenomenon in Colombian
      rivers and could represent a risk factor for human consumers.

PMID- 16650598
TI  - Identification and partial purification of serologically defined Boophilus
      microplus larval antigens by natural ectoparasite exposure.
AB  - In an effort to identify life-stage specific Boophilus microplus proteins that
      elicit a humoral response in cattle, soluble proteins were extracted from 10- to
      14-day-old larvae and subsequently fractionated by size-exclusion chromatography
      and reverse-phase high pressure liquid chromatography. Several antigens were
      identified by Western blotting as potentially shared with other ixodid tick
      species since antibodies to these proteins were present in sera of calves not
      previously exposed to B. microplus. Six putative B. microplus-specific antigens
      were identified by antibodies in the sera of calves repeatedly exposed to B.
      microplus larvae. One of the antigens, a 19.1 kDa protein, was used in the
      development of a diagnostic kELISA for previous exposure to B. microplus. The
      19.1 kDa protein did not have tryptic protease activity or inhibit bovine trypsin
      activity, but appeared to be allergenic in that a partially pure fraction
      elicited immediate-type hypersensitivity responses in calves previously exposed
      to B. microplus.

PMID- 16650599
TI  - Schistosoma japonicum eggs survive passage through dogs and chickens.
AB  - The present study sought to elucidate whether Schistosoma japonicum eggs could
      survive a passage through dogs and chickens. Three dogs and three chickens were
      used for the experiment. The dogs were allowed to eat goat faeces containing 80
      S. japonicum eggs per gram. The chickens were given 2 ml of water containing more
      than 100 S. japonicum eggs per ml. The hatchability of the eggs was 51.8% prior
      to administration. All faeces were collected for 3 days from the dogs and for 2
      days from the chickens and egg excretion and hatchability were measured. The
      results showed that nearly 50% of the eggs administered to the dogs were
      recovered in the faeces during the first 2 days and during the first 25 h 39% of
      the recovered eggs were viable and able to hatch. In the chickens 9% of the
      administered eggs were recovered within 27 h and within the first 3.5 h after
      administration 19% of the recovered eggs were viable and able to hatch. The
      results suggest that both dogs and chickens may act as transport hosts for S.
      japonicum in endemic areas.

PMID- 16650600
TI  - Extracellular signal regulated MAP-kinase signalling in osmotically stressed
      trout hepatocytes.
AB  - Activation of the extracellular signal-regulated MAP-kinase (ERK) by anisoosmotic
      conditions, the underlying signalling pathways, and the role of protein kinases
      in cell volume regulation were investigated in trout hepatocytes. While
      hyperosmolarity left phosphorylated ERK (pERK) levels unaffected, hypoosmolarity
      caused a significant increase of pERK within 2 min which peaked at around 30 min.
      Chelating extracellular Ca2+ to prevent the influx of Ca2+ associated with
      swelling reduced iso- and abolished hypoosmotic ERK activation. Similarly,
      inhibiting the ERK activator MEK, tyrosine kinases, or PKC inhibited the increase
      of pERK. In contrast, exposing cells to chelerytrine or staurosporine, PKC
      inhibitors of little specificity, increased pERK independently from osmotic
      conditions. Blocking PI3 kinase, application of 8-Br-cAMP, exposure to a P
      receptor antagonist, and inhibition of p38 MAP-kinase had no effect on ERK
      activity. A significant reduction of regulatory volume decrease (RVD) after
      hypoosmotic swelling caused by MEK-inhibition and an even more pronounced
      reduction due to p38 inhibition indicates a role for MAP-kinases in volume
      regulation, but a lack of correlation between the impact of protein kinase
      inhibitors on pERK levels and on RVD suggests that ERK may merely modulate volume
      recovery. Immunocytochemical detection of pERK indicated cytoplasmic activation,
      but no nuclear accumulation within 30 min, supporting the notion that ERK exerts
      non-genomic effects. Overall, our data underscore the complexity of hypoosmotic
      ERK signalling and suggest a role of ERK and p38 in acute cell volume regulation.

PMID- 16650601
TI  - Concentration-dependent effects of anticonvulsant enaminone methyl 4-(4'
      bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability in
      vitro.
AB  - Enaminones are a novel group of compounds some of which possess anticonvulsant
      activity in in vivo animal models of seizures. We recently reported that some
      enaminones, including methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo
      1-oate, depress glutamate-mediated excitatory synaptic transmission and that this
      may contribute to their anticonvulsant activity [Kombian SB, Edafiogho IO,
      Ananthalakshmi KVV (2005) Anticonvulsant enaminones depress excitatory synaptic
      transmission in the rat brain by enhancing extracellular GABA levels. Br J
      Pharmacol 145:945-953]. Here we studied the effects of methyl 4-(4'
      bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate, on the excitability of male
      rat (Sprague-Dawley) nucleus accumbens and hippocampal cells in vitro using whole
      cell patch clamp recording techniques. At low, therapeutically relevant
      concentrations (0.3-10 microM), methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6
      methyl-2-oxo-1-oate reversibly suppressed action potential firing rate in a
      concentration-dependent manner. This action potential suppression was present
      when GABA(A), GABA(B) and glutamate receptors were blocked with their
      antagonists. Furthermore, methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2
      oxo-1-oate suppressed tetrodotoxin-sensitive sodium currents in these cells. At
      concentrations >/=100 microM, it induced inward currents and increased action
      potential firing frequency. The inward currents were without changes in input
      resistance and did not reverse polarity between -120 and -40 mV. These currents
      were independent of extracellular potassium, but were absent when extracellular
      sodium was replaced by choline and finally, were occluded by pretreatment with
      ouabain (200 microM). We conclude that methyl 4-(4'-bromophenyl)aminocyclohex-3
      en-6-methyl-2-oxo-1-oate directly inhibits action potential firing at
      therapeutically relevant concentrations by suppressing tetrodotoxin-sensitive
      sodium currents, while inducing an ouabain-sensitive current at high
      concentrations to excite neurons. These two actions of methyl 4-(4'
      bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability
      would have therapeutic implications in future clinical use of enaminones as
      anticonvulsants in seizure disorders.

PMID- 16650602
TI  - Vagus nerve stimulation does not affect spatial memory in fast rats, but has both
      anti-convulsive and pro-convulsive effects on amygdala-kindled seizures.
AB  - Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy.
      Using a seizure-prone Fast-kindling rat strain with known comorbid behavioral
      features, we investigated the effects of VNS on spatial memory, epileptogenesis,
      kindled seizures and body weight. Electrodes were implanted in both amygdalae and
      around the left vagus nerve of 17 rats. Following recovery, rats were tested in
      the Morris water-maze utilizing a fixed platform paradigm. The VNS group received
      2 h of stimulation prior to entering the Morris water-maze. Rats were then tested
      in the kindling paradigm wherein the VNS group received 2 h of stimulation prior
      to daily kindling stimulation. Finally, the abortive effects of acute VNS against
      kindling-induced seizures were determined in fully kindled rats by applying VNS
      immediately after the kindling pulse. Body weight, water consumption and food
      intake were measured throughout. Memory performance in the Morris water-maze was
      not different between control and vagus nerve stimulation rats. Similarly,
      kindling rate was unaffected by antecedent VNS. However, pro-convulsive effects
      (P<0.05) were noted, when VNS was administered prior to the kindling pulse in
      fully kindled rats. Yet, paradoxically, VNS showed anti-convulsant effects
      (P<0.01) in those rats when applied immediately after the kindling stimulus. Body
      weight was significantly lower throughout kindling (P<0.01) in VNS-treated rats
      compared with controls, which was associated with reduced food intake (P<0.05),
      but without difference in water consumption. VNS appears to be devoid of
      significant cognitive side effects in the Morris water-maze in Fast rats.
      Although VNS exhibited no prophylactic effect on epileptogenesis or seizure
      severity when applied prior to the kindling stimulus, it showed significant anti
      convulsant effects in fully kindled rats when applied after seizure initiation.
      Lastly, VNS prevented the weight gain associated with kindling through reduced
      food intake.

PMID- 16650603
TI  - A model of posttraumatic epilepsy induced by lateral fluid-percussion brain
      injury in rats.
AB  - Although traumatic brain injury is a major cause of symptomatic epilepsy, the
      mechanism by which it leads to recurrent seizures is unknown. An animal model of
      posttraumatic epilepsy that reliably reproduces the clinical sequelae of human
      traumatic brain injury is essential to identify the molecular and cellular
      substrates of posttraumatic epileptogenesis, and perform preclinical screening of
      new antiepileptogenic compounds. We studied the electrophysiologic, behavioral,
      and structural features of posttraumatic epilepsy induced by severe, non
      penetrating lateral fluid-percussion brain injury in rats. Data from two
      independent experiments indicated that 43% to 50% of injured animals developed
      epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency
      was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s.
      Behavioral seizure severity increased over time in the majority of animals.
      Secondarily-generalized seizures comprised an average of 66+/-37% of all
      seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of
      animals with posttraumatic epilepsy compared with those subjected to traumatic
      brain injury without epilepsy. Stereologic cell counts indicated a loss of
      dentate hilar neurons ipsilaterally following traumatic brain injury. Our data
      suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after
      severe non-penetrating fluid-percussion brain injury in rats, and that the
      lateral fluid percussion model can serve as a clinically-relevant tool for
      pathophysiologic and preclinical studies.

PMID- 16650604
TI  - Afferent regulation of oxidative stress in the chick cochlear nucleus.
AB  - The chick auditory brain stem has been a useful model system for examining the
      afferent-dependent signals that regulate postsynaptic neurons. Like other sensory
      systems, compromised afferent input results in rapid death and atrophy of
      postsynaptic neurons. The present paper explores the possible contributions of an
      oxidative stress pathway in determining neuronal fate following deafferentation.
      Levels of reactive oxygen species, lipid damage measured by 4-hydroxynonenal
      formation, and a compensatory reactive oxygen species-induced response regulated
      by glutathione s transferase M1 and the reactive oxygen species-sensitive
      transcriptional factor, nuclear respiratory factor 1 were examined. Unilateral
      cochlea removal surgery was performed on young posthatch chicks. Labeling in the
      cochlear nucleus, nucleus magnocellularis, on opposite sides of the same tissue
      sections were compared by densitometry. The results showed a dramatic increase in
      reactive oxygen species in the deafferented nucleus magnocellularis by 6 h
      following cochlea removal. This increase in reactive oxygen species was
      accompanied by lipid damage and a compensatory upregulation of both glutathione s
      transferase M1 and nuclear respiratory factor 1. Double-labeling revealed that
      glutathione s transferase M1 expression was highest in neurons that were likely
      to survive deafferentation, as assessed immunocytochemically with Y10b, a marker
      for ribosomal integrity. Together, these data suggest reactive oxygen species are
      generated and a compensatory detoxifying pathway is upregulated in the first few
      hours following deafferentation. This is consistent with the hypothesis that
      oxidative stress plays a role in determining whether a given neuron survives
      following deafferentation.

PMID- 16650605
TI  - Intron retention as an alternative splice variant of the rat urocortin 1 gene.
AB  - Urocortin 1, highly conserved metazoan gene of the corticotropin-releasing
      hormone family, is a simple gene structured in two exons and the corresponding
      intron. The urocortin 1 prepropeptide is entirely coded in the second exon.
      Preliminary non-isotopic in situ hybridization experiments with an
      oligonucleotide complementary to an intron sequence of the urocortin 1 gene
      showed a significant cytoplasmic-like staining, suggesting the occurrence of an
      intron-retained urocortin 1 transcript. This observation prompted us to study
      whether the urocortin 1 gene presents alternative splicing by intron retention
      event. Confocal fluorescent in situ hybridization for urocortin 1 RNA and the use
      of the specific DNA dye TOPRO-3 allowed us to show significant expression of the
      intron-retained urocortin 1 transcript that did not colocalize with TOPRO-3
      staining indicating a cytoplasmic localization for the intron-retained urocortin
      1 transcript. The natural occurrence of a polyadenylated intron-retained
      urocortin 1 RNA was further documented by reverse transcriptase polymerase chain
      reaction (PCR), primed with oligo(dT), of total RNA extracted from three brain
      regions, a midbrain region containing the Edinger-Westphal nucleus, cerebellum
      and prefrontal cortex. In the three brain regions studied, it was possible to
      amplify both intron-less as well as intron-retained urocortin 1 transcripts. The
      use of PCR primers that simultaneously amplify both urocortin 1 transcripts
      allowed us to show that the expression of both urocortin 1 transcripts differs
      among the brain regions analyzed, suggesting a tissue specific regulation of this
      alternative splicing. In silico analysis of the five known mammalian urocortin 1
      genomic sequences showed high conservation of the urocortin 1 intron sequence.
      Further studies should investigate the regulation of this intron retention event
      and its consequence for the functionality of the urocortin 1 gene.

PMID- 16650606
TI  - Mild, non-lesioning transient hypoxia in the newborn rat induces delayed brain
      neurogenesis associated with improved memory scores.
AB  - Although neonatal hypoxia can lead to brain damage, mild hypoxic episodes may be
      beneficial, as illustrated by tolerance induction by preconditioning, a process
      that might involve neurogenesis. To examine if brief hypoxia in newborn rats
      could stimulate the generation of neurons, pups were exposed for 5 min to 100%
      N2. Cell density and apoptosis were monitored in various brain regions and cell
      proliferation was studied by the incorporation of bromodeoxyuridine. Hypoxia did
      not result in detectable cell death but promoted cell proliferation in the
      ensuing three weeks in the subventricular zone and hippocampal dentate gyrus,
      with increased cell density in hippocampus CA1 pyramidal cells and granular layer
      of the dentate gyrus. Newly generated cells expressed neuronal markers (NeuroD or
      neuronal nuclear antigen) and were able to migrate from germinative zones to
      specific sites, in particular from the subventricular zone to the CA1 layer along
      the posterior periventricle. Neurogenesis was associated with an early activation
      of the extracellular regulated kinase 1/2 pathway, and pre-hypoxic administration
      of U0126, an inhibitor of mitogen-activated protein kinase kinase, impaired
      hypoxia effect on cell proliferation. Neurobehavioral capacities of hypoxic rats
      paralleled those of controls, but early exposure to hypoxia was associated with
      significantly improved memory retrieval scores at 40 days. In conclusion, brief
      neonatal hypoxia may trigger delayed generation of potentially functional neurons
      without concomitant cell death. This may constitute an interesting model for
      studying cell key events involved in the induction of neurogenesis.

PMID- 16650607
TI  - Insulin-like growth factor I interfaces with brain-derived neurotrophic factor
      mediated synaptic plasticity to modulate aspects of exercise-induced cognitive
      function.
AB  - The ability of exercise to benefit neuronal and cognitive plasticity is well
      recognized. This study reveals that the effects of exercise on brain neuronal and
      cognitive plasticity are in part modulated by a central source of insulin-like
      growth factor-I. Exercise selectively increased insulin-like growth factor-I
      expression without affecting insulin-like growth factor-II expression in the rat
      hippocampus. To determine the role that insulin-like growth factor-I holds in
      mediating exercise-induced neuronal and cognitive enhancement, a specific
      antibody against the insulin-like growth factor-I receptor was used to block the
      action of insulin-like growth factor-I in the hippocampus during a 5-day
      voluntary exercise period. A two-trial-per-day Morris water maze was performed
      for five consecutive days, succeeded by a probe trial 2 days later. Blocking
      hippocampal insulin-like growth factor-I receptors did not significantly
      attenuate the ability of exercise to enhance learning acquisition, but abolished
      the effect of exercise on augmenting recall. Blocking the insulin-like growth
      factor-I receptor significantly reversed the exercise-induced increase in the
      levels of brain-derived neurotrophic factor mRNA and protein and pro-brain
      derived neurotrophic factor protein, suggesting that the effects of insulin-like
      growth factor-I may be partially accomplished by modulating the precursor to the
      mature brain-derived neurotrophic factor. A molecular analysis revealed that
      exercise significantly elevated proteins downstream to brain-derived neurotrophic
      factor activation important for synaptic function, i.e. synapsin I, and signal
      transduction cascades associated with memory processes, i.e. phosphorylated
      calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein
      kinase II. Blocking the insulin-like growth factor-I receptor abolished these
      exercise-induced increases. Our results illustrate a possible mechanism by which
      insulin-like growth factor-I interfaces with the brain-derived neurotrophic
      factor system to mediate exercise-induced synaptic and cognitive plasticity.

PMID- 16650608
TI  - Methamphetamine-induced cell death: selective vulnerability in neuronal
      subpopulations of the striatum in mice.
AB  - Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an
      indirect dopamine agonist. In the striatum, METH has been shown to cause long
      lasting neurotoxic damage to dopaminergic nerve terminals and recently, the
      degeneration and death of striatal cells. The present study was undertaken to
      identify the type of striatal neurons that undergo apoptosis after METH. Male
      mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h
      later. To demonstrate that METH induces apoptosis in neurons, we combined
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining with immunohistofluorescence for the neuronal marker neuron-specific
      nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout
      the striatum. METH induces apoptosis in approximately 25% of striatal neurons.
      Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial,
      dorsolateral and ventrolateral quadrants of the striatum did not reveal
      anatomical preference. The type of striatal neuron undergoing cell death was
      determined by combining TUNEL with immunohistofluorescence for selective markers
      of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr
      32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH
      induces apoptosis in approximately 21% of dopamine- and cAMP-regulated
      phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45%
      of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of
      cholinergic neurons in the dorsal-medial striatum. In contrast, the SST-positive
      interneurons were refractory to METH-induced apoptosis. Finally, the amount of
      cell loss determined with Nissl staining correlated with the amount of TUNEL
      staining in the striatum of METH-treated animals. In conclusion, some of the
      striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons
      were removed by apoptosis in the aftermath of METH. This imbalance in the
      populations of striatal neurons may lead to functional abnormalities in the
      output and processing of neural information in this part of the brain.

PMID- 16650609
TI  - Association of connexin36 and zonula occludens-1 with zonula occludens-2 and the
      transcription factor zonula occludens-1-associated nucleic acid-binding protein
      at neuronal gap junctions in rodent retina.
AB  - Most gap junctions between neurons in mammalian retina contain abundant
      connexin36, often in association with the scaffolding protein zonula occludens-1.
      We now investigate co-association of connexin36, zonula occludens-1, zonula
      occludens-2 and Y-box transcription factor 3 (zonula occludens-1-associated
      nucleic acid-binding protein) in mouse and rat retina. By immunoblotting, zonula
      occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were
      both detected in retina, and zonula occludens-2 in retina was found to co
      immunoprecipitate with connexin36. By immunofluorescence, the four proteins
      appeared as puncta distributed in the plexiform layers. In the inner plexiform
      layer, most connexin36-puncta were co-localized with zonula occludens-1, and many
      were co-localized with zonula occludens-1-associated nucleic acid-binding
      protein. Moreover, zonula occludens-1-associated nucleic acid-binding protein was
      often co-localized with zonula occludens-1. Nearly all zonula occludens-2-puncta
      were positive for connexin36, zonula occludens-1 and zonula occludens-1
      associated nucleic acid-binding protein. In the outer plexiform layer, connexin36
      was also often co-localized with zonula occludens-1-associated nucleic acid
      binding protein. In connexin36 knockout mice, labeling of zonula occludens-1 was
      slightly reduced in the inner plexiform layer, zonula occludens-1-associated
      nucleic acid-binding protein was decreased in the outer plexiform layer, and both
      zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2
      were markedly decreased in the inner sublamina of the inner plexiform layer,
      whereas zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated
      nucleic acid-binding protein puncta persisted and remained co-localized in the
      outer sublamina of the inner plexiform layer. By freeze-fracture replica
      immunogold labeling, connexin36 was found to be co-localized with zonula
      occludens-2 within individual neuronal gap junctions. In addition, zonula
      occludens-1-associated nucleic acid-binding protein was abundant in a portion of
      ultrastructurally-defined gap junctions throughout the inner plexiform layer, and
      some of these junctions contained both connexin36 and zonula occludens-1
      associated nucleic acid-binding protein. These distinct patterns of connexin36
      association with zonula occludens-1, zonula occludens-2 and zonula occludens-1
      associated nucleic acid-binding protein in different sublaminae of retina, and
      differential responses of these proteins to connexin36 gene deletion suggest
      differential regulatory and scaffolding roles of these gap junction accessory
      proteins. Further, the persistence of a subpopulation of zonula occludens
      1/zonula occludens-2/zonula occludens-1-associated nucleic acid-binding protein
      co-localized puncta in the outer part of the inner plexiform layer of connexin36
      knockout mice suggests close association of these proteins with other structures
      in retina, possibly including gap junctions composed of an as-yet-unidentified
      connexin.

PMID- 16650610
TI  - Increased matrix-metalloproteinase-2 and matrix-metalloproteinase-9 expression in
      the brain of dystrophic mdx mouse.
AB  - Brain edema and severe alterations of the glial and endothelial cells have
      recently been demonstrated in the dystrophin-deficient mdx mouse, an experimental
      model of Duchenne muscular dystrophy, and an increase in microvessel density in
      patients affected by Duchenne muscular dystrophy has also been shown. In order to
      further elucidate the mechanisms underlying the angiogenetic processes occurring
      in Duchenne muscular dystrophy, in this study we analyzed matrix
      metalloproteinase-2 and -9 expression in the brain of 20-month-old mdx and
      control mice by means of immunohistochemistry, in situ hybridization,
      immunoblotting and gelatin zymography. Moreover, we studied vascular endothelial
      growth factor expression by means of Western blot and immunohistochemistry, and
      by dual immunofluorescence using anti-vascular endothelial growth factor and anti
      matrix-metalloproteinase-2 and-9 antibodies. Ultrastructural features of the
      brain choroidal plexuses were evaluated by electron microscopy. Spatial
      relationships between endothelium and astrocyte processes were studied by
      confocal laser microscopy, using an anti-CD31 antibody as a marker of endothelial
      cells, and anti-glial fibrillary acidic protein (GFAP) as a marker of glial
      cells. The results demonstrate that high expression of matrix-metalloproteinase-2
      and matrix-metalloproteinase-9 protein content occurs in mdx brain and in
      choroidal plexuses where, by in situ hybridization, matrix-metalloproteinase-2
      and matrix-metalloproteinase-9 mRNA was localized in the epithelial cells.
      Moreover, matrix-metalloproteinase-2 mRNA was found in both mdx perivascular
      astrocytes and blood vessels, while matrix-metalloproteinase-9 mRNA was localized
      in mdx vessels. Through zymography, increased expression of matrix
      metalloproteinase-2 and matrix-metalloproteinase-9 was found in mdx brain
      compared with the controls. These enhanced matrix-metalloproteinase levels in mdx
      mice were found to be associated with increased vascular endothelial growth
      factor expression, as determined by immunoblotting and immunocytochemistry and
      with ultrastructural alterations of the mdx choroidal epithelial cells and brain
      vessels, as previously reported [Nico B, Frigeri A, Nicchia GP, Corsi P, Ribatti
      D, Quondamatteo F, Herken R, Girolamo F, Marzullo A, Svelto M, Roncali L (2003)
      Severe alterations of endothelial and glial cells in the blood-brain barrier of
      dystrophic mdx mice. Glia 42:235-251]. Indeed, in the mdx epithelial cells of the
      plexuses, the apical microvilli were located on the lateral membranes, whereas in
      the controls they were uniformly distributed over the free ventricular surface.
      Moreover, by dual immunofluorescence, a colocalization of vascular endothelial
      growth factor and matrix-metalloproteinase-2 and matrix-metalloproteinase-9 was
      found in the ependymal and epithelial cells of plexuses in mdx mice and, under
      confocal laser microscopy, mdx CD-31 positive vessels were enveloped by less GFAP
      positive astrocyte processes than the controls. Overall, these data point to a
      specific pathogenetic role of matrix-metalloproteinase-2 and matrix
      metalloproteinase-9 in neurological dysfunctions associated with Duchenne
      muscular dystrophy.

PMID- 16650611
TI  - Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons.
AB  - To determine the synaptic source of the respiratory-related activity of laryngeal
      motoneurons, spike-triggered averaging of the membrane potentials of laryngeal
      motoneurons was conducted using spikes of respiratory neurons located between the
      Botzinger complex and the rostral ventral respiratory group as triggers in
      decerebrate, paralyzed cats. We identified one excitatory and two inhibitory
      sources for inspiratory laryngeal motoneurons, and two inhibitory sources for
      expiratory laryngeal motoneurons. In inspiratory laryngeal motoneurons,
      monosynaptic excitatory postsynaptic potentials were evoked by spikes of
      inspiratory neurons with augmenting firing patterns, and monosynaptic inhibitory
      postsynaptic potentials (IPSPs) were evoked by spikes of expiratory neurons with
      decrementing firing patterns and by spikes of inspiratory neurons with
      decrementing firing patterns. In expiratory laryngeal motoneurons, monosynaptic
      IPSPs were evoked by spikes of inspiratory neurons with decrementing firing
      patterns and by spikes of expiratory neurons with augmenting firing patterns. We
      conclude that various synaptic inputs from respiratory neurons contribute to
      shaping the respiratory-related trajectory of membrane potential of laryngeal
      motoneurons.

PMID- 16650612
TI  - Memory-dependent c-Fos expression in the nucleus accumbens and extended amygdala
      following the expression of a conditioned taste aversive in the rat.
AB  - Retrieving the memory of a conditioned taste aversion involves multiple forebrain
      areas. Although the amygdala clearly plays a role in the expression of a
      conditioned taste aversion, critical regions, downstream from the amygdala remain
      to be defined. To this end, Fos immunoreactivity was used in the rat to explore
      forebrain structures associated with retrieval that have an anatomical
      relationship with the amygdala. The results showed that expression of a
      conditioned taste aversion to 0.5 M sucrose elicited neuronal activation in the
      nucleus accumbens and in a complex of structures collectively referred to as the
      extended amygdala. The posterior hypothalamus and parasubthalamic nucleus, which
      receive inputs from the extended amygdala, were also activated upon re-exposure
      to the sucrose conditioned stimulus. Fos immunoreactivity did not increase in
      these regions in response to an innately aversive tastant, quinine hydrochloride
      (conditioned stimulus control), nor to LiCl-induced visceral stimulation in
      unconditioned animals (unconditioned stimulus control). In addition, these
      regions did not respond to the sucrose conditioned stimulus in sham-conditioned
      animals. These results suggest that conditioned and innately aversive tastes are
      differentially processed in the forebrain circuitry that includes the nucleus
      accumbens and extended amygdala.

PMID- 16650613
TI  - The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either
      epileptogenesis or tyrosine receptor kinase B activation in the kindling model.
AB  - The kindling model of epilepsy is a form of neuronal plasticity induced by
      repeated induction of pathological activity in the form of focal seizures. A
      causal role for the neurotrophin receptor, tyrosine receptor kinase B, in
      epileptogenesis is supported by multiple studies of the kindling model. Not only
      is tyrosine receptor kinase B required for epileptogenesis in this model but
      enhanced activation of tyrosine receptor kinase B has been identified in the
      hippocampus in multiple models of limbic epileptogenesis. The neurotrophin ligand
      mediating tyrosine receptor kinase B activation during limbic epileptogenesis is
      unknown. We hypothesized that neurotrophin-4 (NT4) activates tyrosine receptor
      kinase B in the hippocampus during epileptogenesis and that NT4-mediated
      activation of tyrosine receptor kinase B promotes limbic epileptogenesis. We
      tested these hypotheses in NT4-deficient mice with a targeted deletion of NT4
      gene using the kindling model. The development and persistence of amygdala
      kindling were examined in wild type (+/+) and NT4 null mutant (-/-) mice. No
      differences were found between +/+ and -/- mice with respect to any facet of the
      development or persistence of kindling. Despite the absence of NT4, activation of
      the tyrosine receptor kinase B receptor in the mossy fiber pathway as assessed by
      phospho-trk immunohistochemistry was equivalent to that of +/+ mice. Together
      these findings demonstrate that NT4 is not required for limbic epileptogenesis
      nor is it required for activation of tyrosine receptor kinase B in hippocampus
      during limbic epileptogenesis.

PMID- 16650614
TI  - Descending facilitation from the rostral ventromedial medulla maintains nerve
      injury-induced central sensitization.
AB  - Nerve injury can produce hypersensitivity to noxious and normally innocuous
      stimulation. Injury-induced central (i.e. spinal) sensitization is thought to
      arise from enhanced afferent input to the spinal cord and to be critical for
      expression of behavioral hypersensitivity. Descending facilitatory influences
      from the rostral ventromedial medulla have been suggested to also be critical for
      the maintenance, though not the initiation, of experimental neuropathic pain. The
      possibility that descending facilitation from the rostral ventromedial medulla is
      required for the maintenance of central sensitization was examined by determining
      whether ablation of mu-opioid receptor-expressing cells within the rostral
      ventromedial medulla prevented the enhanced expression of repetitive touch-evoked
      FOS within the spinal cord of animals with spinal nerve ligation injury as well
      as nerve injury-induced behavioral hypersensitivity. Rats received a single
      microinjection of vehicle, saporin, dermorphin or dermorphin-saporin into the
      rostral ventromedial medulla and 28 days later, underwent either sham or spinal
      nerve ligation procedures. Animals receiving rostral ventromedial medulla
      pretreatment with vehicle, dermorphin or saporin that were subjected to spinal
      nerve ligation demonstrated both thermal and tactile hypersensitivity, and showed
      significantly increased expression of touch-evoked FOS in the dorsal horn
      ipsilateral to nerve injury compared with sham-operated controls at days 3, 5 or
      10 post-spinal nerve ligation. In contrast, nerve-injured animals pretreated with
      dermorphin-saporin showed enhanced behaviors and touch-evoked FOS expression in
      the spinal dorsal horn at day 3, but not days 5 and 10, post-spinal nerve
      ligation when compared with sham-operated controls. These results indicate the
      presence of nerve injury-induced behavioral hypersensitivity associated with
      nerve injury-induced central sensitization. Further, the results demonstrate the
      novel concept that once initiated, maintenance of nerve injury-induced central
      sensitization in the spinal dorsal horn requires descending pain facilitation
      mechanisms arising from the rostral ventromedial medulla.

PMID- 16650615
TI  - Distribution and ultrastructural localization of GEC1 in the rat CNS.
AB  - We have previously demonstrated that GEC1 interacts with the kappa opioid
      receptor and GEC1 expression enhances cell surface expression of the receptor in
      Chinese hamster ovary cells. In this study, we generated an antiserum (PA629)
      directed against GEC1 in rabbits, characterized its specificity, and investigated
      distribution of GEC1 in tissues and in brain regions and spinal cord and its
      subcellular localization in hypothalamic neurons in the rat. Immunofluorescence
      staining demonstrated that PA629 recognized HA-GEC1 transfected into Chinese
      hamster ovary cells, but not HA-GABARAP or HA-GATE-16, although the three share
      high homology. Pre-incubation of PA629 with GST-GEC1, but not GST, abolished the
      staining. In immunoblotting, affinity-purified PA629 (PA629p) recognized GEC1,
      GABARAP and GATE-16. GEC1 migrated slower than GABARAP and GATE-16, with a M(r)
      of 16 kDa for GEC1 and M(r) of 14 kDa for GABARAP and GATE-16. Immunoblotting
      results showed that GEC1 level was higher in liver and brain than in lung and
      heart, and very low in kidney and skeletal muscle. GEC1 was present in all rat
      brain regions examined and spinal cord. Immunohistochemistry demonstrated that
      GEC1 immunoreactivity was distributed ubiquitously in the rat CNS with highly
      intense immunoreactivity in various brain nuclei and motor neurons of the spinal
      cord. Ultrastructural examination of neurons in the paraventricular nucleus of
      the hypothalamus showed that GEC1 was associated with endoplasmic reticulum and
      Golgi apparatus and distributed along plasma membranes and in cytosol. Coupled
      with our previous observation that GEC1 interacts with N-ethylmaleimide-sensitive
      factor, these findings strongly suggest that GEC1 functions in intracellular
      trafficking in the biosynthesis pathway and perhaps also the endocytic pathway.
      The widespread distribution of GEC1 suggests that GEC1 may be associated with
      many proteins, in addition to the kappa opioid receptor.

PMID- 16650616
TI  - Participation of estradiol and progesterone in the retrograde labeling of
      pubococcygeus motoneurons of the female rat.
AB  - Retrograde labeling with horseradish peroxidase conjugated to wheat germ
      agglutinin showed that the pubococcygeus muscles of the female rat are innervated
      by a population of motoneurons located in a column approximately 2 mm in length
      in the central region of lamina IX of the sixth lumbar-first sacral spinal cord
      segments. These neurons have a dendritic distribution that projects to the
      lateral, medial and ventral regions of the gray matter. Values for soma size,
      primary dendrite length and arborization area obtained from intact animals that
      were in diestrous-2, were significantly reduced following ovariectomy. After
      hormone priming of the ovariectomized animals with estradiol benzoate and
      progesterone, an additional injection of estradiol benzoate alone or followed by
      progesterone increased the labeled length of the primary dendrites distributed to
      the lateral, but not to the medial or ventral regions of the gray matter in the
      spinal cord. However, dendritic labeling was not significantly increased when
      only progesterone was additionally injected. It therefore seems that
      pubococcygeus muscle motoneurons of the female rat are sensitive to the effects
      of gonadal hormones.

PMID- 16650617
TI  - Plasticity in the expression of the steroid receptor coactivator 1 in the
      Japanese quail brain: effect of sex, testosterone, stress and time of the day.
AB  - Analysis of nuclear receptor action on the eukaryotic genome highlights the
      importance of coactivators on gene transcription. The steroid receptor
      coactivator-1 in particular is the focus of an intense research and physiological
      or behavioral studies have confirmed that it plays a major role in the modulation
      of steroid and thyroid receptors activity. However, little is known about the
      regulation of steroid receptor coactivator-1 expression the brain. The goal of
      this study was to determine the potential factors modulating steroid receptor
      coactivator-1 synthesis in Japanese quail by quantification of its mRNA with real
      time quantitative polymerase chain reaction and of the corresponding protein via
      Western blotting. Contrary to previously published results from our laboratory
      [Charlier TD, Lakaye B, Ball GF, Balthazart J (2002) The steroid receptor
      coactivator SRC-1 exhibits high expression in steroid-sensitive brain areas
      regulating reproductive behaviors in the quail brain. Neuroendocrinology 76:297
      315], we found here that sexually mature females had a higher concentration of
      steroid receptor coactivator-1 in the preoptic area/hypothalamus compared with
      males. Steroid receptor coactivator-1 expression in the male preoptic
      area/hypothalamus was up-regulated by testosterone and tended to be decreased by
      stress. We also identified a significant correlation between the time of the day
      and the expression of the coactivator in the optic lobes, hippocampus,
      telencephalon and hindbrain but the pattern of changes in expression as a
      function of the time of the day varied from one brain area to another. Together,
      these data support the idea that steroid receptor coactivator-1 is not
      constitutively expressed but rather is finely regulated by steroids, stress and
      possibly other unidentified factors.

PMID- 16650618
TI  - Estrogen-triggered activation of GTP cyclohydrolase 1 gene expression: role of
      estrogen receptor subtypes and interaction with cyclic AMP.
AB  - Guanosinetriphosphate cyclohydrolase I (GTPCH) catalyzes the initial step in the
      de novo biosynthesis of (6R)-5,6,7,8-tetrahydrobiopterin, an important
      determinant of the rate of catecholamine and nitric oxide biosynthesis.
      Administration of estrogen in vivo was found to elevate GTPCH mRNA levels in
      several catecholaminergic locations. To examine the mechanism, PC12 cells were co
      transfected with a reporter construct containing 2988 bp of rat GTPCH promoter
      fused to luciferase gene, and expression vectors for estrogen receptors. Addition
      of 2.5-20 nM of 17 beta-estradiol increased GTPCH promoter-driven luciferase
      activity in the presence of either estrogen receptor alpha or estrogen receptor
      beta indicating, for the first time, that 17 beta-estradiol can regulate GTPCH
      gene expression via transcriptional mechanisms. However, there were differences
      in dose dependence and time course with estrogen receptor alpha or estrogen
      receptor beta. With estrogen receptor alpha, the effect was greater with lower
      doses of 17 beta-estradiol. At the same dose, the response with estrogen receptor
      beta was observed somewhat earlier than with estrogen receptor alpha and with 20
      nM 17 beta-estradiol was effective even after 6 h. These responses to 17 beta
      estradiol required estrogen receptors and specific agonists for estrogen receptor
      alpha and estrogen receptor beta, 4,4,4,-(4-propil-[1H-pyrazole-1,3,5-triyl)tris
      phenol and 2,3-bis[4-hydroxyphenyl]propionitrile respectively, triggered
      increased GTPCH promoter activity. In addition, neither estradiol, nor the
      selective agonists activated GTPCH promoter without transfection of appropriate
      estrogen receptor expression vectors. Addition of 17 beta-estradiol, or the
      selective agonists, also elevated endogenous GTPCH mRNA levels. The results
      demonstrate that estrogen can have a direct effect on GTPCH gene expression.
      Although estradiol increased GTPCH promoter activity in the presence of estrogen
      receptors, it attenuated the response of the promoter and endogenous gene to
      cyclic AMP, suggesting the crosstalk between estrogen and cyclic AMP pathways in
      the regulation of GTPCH gene expression. These findings reveal the significance
      of estrogen in modulating regulation of rate limiting enzyme in the (6R)-5,6,7,8
      tetrahydrobiopterin biosynthesis, which may have implications for sex-related
      differences in vulnerability in related disorders.

PMID- 16650619
TI  - Calcium binding protein containing neurons in the gliotic mouse hippocampus with
      special reference to their afferents from the medial septum and the entorhinal
      cortex.
AB  - In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic
      reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons
      was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus. In
      gliotic CA1 area at 60 days, few dendritic branches of calcium binding protein
      immunopositive neurons could be found suggesting reorganization of the afferents
      of surviving calcium binding protein immunopositive neurons. Calbindin,
      calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling
      showed that calcium binding protein immunopositive neurons in gliotic CA1 area at
      60 days were surviving instead of newly generated neurons. Iontophoretic
      injection of Phaseolus vulgaris leucoagglutinin into the medial septum and the
      nucleus of the diagonal band of Broca or the lateral entorhinal cortex showed
      contacts between Phaseolus vulgaris leucoagglutinin immunopositive en passant and
      terminal boutons and surviving calcium binding protein immunopositive neurons in
      the hippocampus. The presence in the gliotic hippocampus of enlarged and/or
      aggregated bouton-like structures 60 days after pilocarpine-induced status
      epilepticus is indicative for the reorganization of connections between the
      hippocampal afferents and surviving hippocampal neurons. This reconstruction
      could be a factor in the ongoing epileptic activity in this model of mesial
      temporal lobe epilepsy.

PMID- 16650620
TI  - Smoking and cognitive change from age 11 to 66 years: a confirmatory
      investigation.
AB  - Previously we reported that smoking is associated with a small relative decline
      in cognition from childhood to old age. In this study we perform confirmatory
      analyses on a further wave of data collected from 298 of the participants, all
      with age 11 IQ scores, at age 66years, 2years after the original observations.
      Non-smokers scored a mean 4.9 memory test and 2.6 information processing speed
      test points and ex-smokers 3.5 memory test and 1.9 information processing speed
      test points higher than current smokers respectively over the two waves of
      testing, equivalent to 4-8% of mean test scores, adjusted for the effects of
      childhood IQ. Across tests a 100l/min higher Peak Expiratory Flow Rate was
      associated with a 3-4% higher test score at ages 64 and 66years. These data
      confirm the adverse effect of smoking on information processing speed, and
      provide new evidence for a similar adverse effect on memory for people in their
      mid-sixties.

PMID- 16650621
TI  - Alcohol expectancies, self-efficacy and coping in an alcohol-dependent sample.
AB  - This study expanded earlier work conducted by this laboratory by examining the
      independent and interactive effects of avoidant coping strategies, positive and
      negative alcohol expectancies and self-efficacy, in predicting volume and
      frequency of alcohol consumption in a sample dependent on alcohol (n=296). Coping
      strategies were found to be salient predictors of frequency of drinking, while
      venting emotion interacted with negative expectancies to predict both volume and
      frequency of drinking. Venting emotion was also found to interact with drinking
      refusal self-efficacy in predicting volume of alcohol consumed. These
      interactions are discussed in terms of the cognitive and behavioural mechanisms
      thought to underlie drinking behaviour.

PMID- 16650622
TI  - Reducing excessive alcohol consumption at university fraternity parties: a cost
      effective incentive/reward intervention.
AB  - The impact of an incentive/reward intervention on college students' intoxication
      from alcohol consumption at fraternity parties was explored using a group
      randomized trial. Participants included 702 college students (447 men, 225 women)
      attending fraternity parties in Blacksburg, VA. Six fraternities were randomly
      assigned to a control or experimental group, and each of these fraternities
      hosted two parties. The three fraternities in the experimental group hosted a
      baseline party first and then hosted an intervention party at which those having
      a blood alcohol concentration (BAC) level below 0.05 were entered in a $100 cash
      lottery. The three fraternities in the control group hosted two control (non
      intervention) parties. For the experimental fraternities, mean BAC levels were
      significantly lower at the intervention parties (M=0.079) than the baseline
      parties (M=0.098) and the percentage of party-goers with a BAC below 0.08 was
      significantly higher at intervention parties (40.1%) than at baseline parties
      (30.6%). This field study supports the efficacy of differential reinforcement in
      controlling student intoxication at party settings.

PMID- 16650623
TI  - Gender differences in adolescents' responses to themes of relaxation in cigarette
      advertising: Relationship to intentions to smoke.
AB  - Studies have shown that increased exposure to cigarette advertising increases
      adolescents' risk of smoking and moreover, that gender may play an important role
      in moderating how cigarette advertisements are viewed and processed. However,
      information about the particular features of cigarette advertising that interact
      with gender to promote smoking among adolescents is scarce. The purpose of this
      study was to examine if gender moderates the degree to which the relaxation
      valence (i.e., degree to which relaxing themes are emphasized) of cigarette
      advertisements is related to smoking intentions in a sample of never smoking
      adolescents. Regardless of brand type (of the seven brands studied), cigarette
      advertisements that displayed highly relaxing images were associated with
      increased intentions to smoke among female adolescents only. These results have
      implications for understanding what features of cigarette advertisements have the
      most influence among different groups of adolescents.

PMID- 16650624
TI  - Effects of partner smoking status and gender on long term abstinence rates of
      patients receiving smoking cessation treatment.
AB  - AIMS: To assess the effect of partner smoking status on the success of a
      cessation program. DESIGN: Prospective cohort. SETTING: Smoking Cessation Unit in
      Hospital of Bellvitge (Hospitalet de Llobregat, Barcelona). PARTICIPANTS: A total
      of 1516 smokers of 10 or more cigarettes who started a smoking cessation program
      between January 1995 and December 2001 were included. MEASUREMENTS: All patients
      gave information about smoking history and smoking partner status. Abstinence was
      determined by carbon monoxide exhaled. FINDINGS: Significant differences were
      found in the abstinence rates at 12 months by smoking partner status: abstinence
      was achieved by 28.3% of patients with smoking partner, and by 46.5% of patients
      without smoking partner (p<0.001). Subjects whose partner was smoking at the
      beginning of the program appear to be more likely to relapse than subjects
      without smoking partners (p<0.001) and this is more pronounced in women than in
      men. However no significant gender differences were found in any group of smoking
      partner status. CONCLUSIONS: Having a smoking partner is a determinant of relapse
      1 year after the beginning of the cessation program. Interacting not just with
      the smoker, but also with his or her partner, could neutralize interpersonal
      influences making smokers more accessible to behavioural and pharmacological
      techniques.

PMID- 16650625
TI  - The use of GEE for analyzing longitudinal binomial data: a primer using data from
      a tobacco intervention.
AB  - Longitudinal study designs in addictive behaviors research are common as
      researchers have focused increasingly on how various explanatory variables affect
      responses over time. In particular, such designs are used in intervention studies
      that have multiple follow-up points. These designs typically involve repeated
      measurement of participants' responses, and thus correlation within each
      participant is expected. Correct inferences can only be obtained by taking into
      account this within-participant correlation between repeated measurements, which
      can complicate the analysis of longitudinal data. In recent years, generalized
      estimating equations (GEE) has become a standard method for analyzing non-normal
      longitudinal data, yet it often is not utilized by addiction researchers. The
      goal of this article is to provide an overview of the GEE approach for analyzing
      correlated binary data for behavioral researchers, using data from an
      intervention study on the prevention of relapse to tobacco smoking.

PMID- 16650626
TI  - Midzonal lesions in yellow fever: a specific pattern of liver injury caused by
      direct virus action and in situ inflammatory response.
AB  - Yellow fever is an acute infectious, non-contagious disease characterized by
      intense vasculopathy and lesions in different organs. In the liver, one of the
      main targets of the virus, the infection induces a characteristic midzonal injury
      characterized by hepatocyte necrosis, apoptosis and steatosis. This
      characteristics pattern of liver injury in yellow fever is also observed in
      conditions of low-flow hypoxia and other infections such as dengue and Rift
      Valley fever. There are no reports in the literature explaining the genesis of
      this peculiar histopathological pattern in yellow fever. Some hypotheses have
      been proposed to explain the mechanism of this midzonal distribution pattern
      observed in the liver such as low-flow hypoxia and tropism of the virus toward
      hepatocytes in this area. These hypotheses are discussed in view of more recent
      findings regarding the pathogenesis of yellow fever and regarding hepatic
      physiopathology, and a new hypothesis is proposed: the midzonal necrosis is
      consequence of action of combined factors mainly the direct cytopathic effect of
      YFV associated with a potent immune response in which CD4+ and CD8+ lymphocytes
      and the cytokines, especially TGF-beta, but also TNF-alpha and IFN-gamma play an
      important role.

PMID- 16650627
TI  - China's human rights and our responsibilities.

PMID- 16650628
TI  - Patient choice stops at inhaled insulin.

PMID- 16650629
TI  - Time for the World Bank to act on malaria.

PMID- 16650630
TI  - Good news for Marburg virus workers.

PMID- 16650631
TI  - Influenza pandemic preparedness: gauging from EU plans.

PMID- 16650632
TI  - The risk of aprotinin: a conflict of evidence.

PMID- 16650633
TI  - The rise and fall of sleeping sickness.

PMID- 16650634
TI  - Management of urethral strictures.

PMID- 16650635
TI  - Syndromic approach for treatment of STIs: time for a change.

PMID- 16650636
TI  - Chemoprevention of breast cancer.

PMID- 16650637
TI  - You need hands.

PMID- 16650638
TI  - Amy Jadesimi. Interview.

PMID- 16650639
TI  - Cuttings.

PMID- 16650640
TI  - UK statistical indifference to military casualties in Iraq.

PMID- 16650641
TI  - UK statistical indifference to military casualties in Iraq.

PMID- 16650642
TI  - Clinical recognition of meningococcal disease.

PMID- 16650643
TI  - Clinical recognition of meningococcal disease.

PMID- 16650645
TI  - Clinical recognition of meningococcal disease.

PMID- 16650646
TI  - The many stigmas of mental illness.

PMID- 16650647
TI  - Is there a doctor aboard?

PMID- 16650648
TI  - Multiple facets of China's health inequality.

PMID- 16650649
TI  - Postexposure protection against Marburg haemorrhagic fever with recombinant
      vesicular stomatitis virus vectors in non-human primates: an efficacy assessment.
AB  - BACKGROUND: Effective countermeasures are urgently needed to prevent and treat
      infections caused by highly pathogenic and biological threat agents such as
      Marburg virus (MARV). We aimed to test the efficacy of a replication-competent
      vaccine based on attenuated recombinant vesicular stomatitis virus (rVSV), as a
      postexposure treatment for MARV haemorrhagic fever. METHODS: We used a rhesus
      macaque model of MARV haemorrhagic fever that produced 100% lethality. We
      administered rVSV vectors expressing the MARV Musoke strain glycoprotein to five
      macaques 20-30 min after a high-dose lethal injection of homologous MARV. Three
      animals were MARV-positive controls and received non-specific rVSV vectors. We
      tested for viraemia, undertook analyses for haematology and serum biochemistry,
      and measured humoral and cellular immune responses. FINDINGS: All five rhesus
      monkeys that were treated with the rVSV MARV vectors as a postexposure treatment
      survived a high-dose lethal challenge of MARV for at least 80 days. None of these
      five animals developed clinical symptoms consistent with MARV haemorrhagic fever.
      All the control animals developed fulminant disease and succumbed to the MARV
      challenge by day 12. MARV disease in the controls was indicated by: high titres
      of MARV (10(3)-10(5) plaque-forming units per mL); development of leucocytosis
      with concurrent neutrophilia at end-stage disease; and possible damage to the
      liver, kidney, and pancreas. INTERPRETATION: Postexposure protection against MARV
      in non-human primates provides a paradigm for the treatment of MARV haemorrhagic
      fever. Indeed, these data suggest that rVSV-based filoviral vaccines might not
      only have potential as preventive vaccines, but also could be equally useful for
      postexposure treatment of filoviral infections.

PMID- 16650650
TI  - How prepared is Europe for pandemic influenza? Analysis of national plans.
AB  - BACKGROUND: The threat of a human pandemic of influenza has prompted urgent
      development of national preparedness plans. We assessed these plans, to judge
      Europe's preparedness for pandemic influenza. METHODS: Published national
      pandemic influenza preparedness plans from the European Union countries, the two
      acceding countries (Bulgaria and Romania), Norway, and Switzerland, were
      evaluated against criteria taken from a WHO checklist. Plans were eligible for
      inclusion if formally published between Jan 1, 2002, and Nov 30, 2005. FINDINGS:
      21 national plans were eligible for inclusion for analysis. Although preparation
      for surveillance, planning and coordination, and communication were good,
      maintenance of essential services, putting plans into action, and public-health
      interventions were probably inadequate. Few countries have addressed in their
      plans the need for collaboration with adjacent countries, despite this being an
      acknowledged imperative. Similarly, plans for the timely distribution of
      available medical supplies are notably absent. INTERPRETATION: Governmental
      commitment in most European countries is strong, and levels of preparedness are
      broadly good. However, gaps in preparedness planning remain, and substantial
      variations exist between countries, with important implications for the region
      and nation states. Improved cooperation between countries may be needed to share
      experience, and to ensure coherence of approaches.

PMID- 16650651
TI  - Rate, extent, and modifiers of spermatogenic recovery after hormonal male
      contraception: an integrated analysis.
AB  - BACKGROUND: Hormonal methods for safe, reliable, and reversible contraception
      based on the suppression of spermatogenesis could soon become available. We have
      investigated the rate, extent, and predictors of reversibility of hormonal male
      contraception. METHODS: We undertook an integrated multivariate time-to-event
      analysis of data from individual participants in 30 studies published in 1990
      2005, in which sperm output was monitored every month until recovery. The primary
      outcome was the time for the sperm concentration to recover to a threshold of 20
      million per mL, an indicator of fertility. We undertook univariate and
      multivariate analyses, using Kaplan-Meier and Cox's methods. FINDINGS: 1549
      healthy eugonadal men who were white (n=965), Asian (almost all Chinese men;
      n=535), or of other origins (n=49) and aged 18-51 years underwent 1283.5 man
      years of treatment and 705 man-years of post-treatment recovery. These data
      represented about 90% of all published data from individuals using androgen or
      androgen-progestagen regimens. The median times for sperm to recover to
      thresholds of 20, 10, and 3 million per mL were 3.4 months (95% CI 3.2-3.5), 3.0
      months (2.9-3.1), and 2.5 months (2.4-2.7), respectively. Multivariate Cox's
      analysis showed higher rates of recovery with older age, Asian origin, shorter
      treatment duration, shorter-acting testosterone preparations, higher sperm
      concentrations at baseline, faster suppression of spermatogenesis, and lower
      blood concentrations of luteinising hormone at baseline. The typical probability
      of recovery to 20 million per mL was 67% (61-72) within 6 months, 90% (85-93)
      within 12 months, 96% (92-98) within 16 months, and 100% within 24 months.
      INTERPRETATION: Hormonal male contraceptive regimens show full reversibility
      within a predictable time course. Various covariables affect the rate but not the
      extent of recovery, although their effect sizes are minor. These data are crucial
      for the further safe and practical development of such regimens.

PMID- 16650652
TI  - Bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia is a chronic lung disease that affects premature
      babies and contributes to their morbidity and mortality. Improved survival of
      very immature infants has led to increased numbers of infants with this disorder.
      This increase puts a heavy burden on health resources since these infants need
      frequent re-admission to hospital in the first 2 years after birth and, even as
      adolescents, have lung-function abnormalities and persistent respiratory
      symptoms. Unlike the original description of the disease in 1967, premature
      infants can develop chronic oxygen dependency without severe, acute respiratory
      distress; this "new bronchopulmonary dysplasia" could be the result of impaired
      postnatal lung growth. Whether such infants subsequently have catch-up lung
      growth, especially if given corticosteroids postnatally, is unknown. No safe and
      effective preventive therapy has been identified, but promising new treatments
      directed either at reducing lung injury or improving lung growth are under study.

PMID- 16650653
TI  - Laser eye surgery for refractive errors.
AB  - Several laser and non-laser refractive surgical procedures have been used to
      modify the shape of the cornea and correct myopia, hyperopia, astigmatism, and
      presbyopia. Introduction of the excimer laser to reshape the cornea has resulted
      in remarkable developments in the correction of these refractive errors. Combined
      with other advanced ophthalmological instruments, laser refractive eye surgery
      has resulted in a substantial rise in the safety, efficacy, and predictability of
      surgical outcomes. Despite these advances, certain limitations and complications
      persist. In this review, we describe the history, preoperative assessment,
      surgical techniques, outcomes, and complications of laser refractive surgery.

PMID- 16650654
TI  - The health migration crisis: the role of four Organisation for Economic
      Cooperation and Development countries.
AB  - The crisis of human resources for health that is affecting low-income countries
      and especially sub-Saharan Africa has been attributed, at least in part, to
      increasing rates of migration of qualified health staff to high-income countries.
      We describe the conditions in four Organisation for Economic Cooperation and
      Development (OECD) health labour markets that have led to increasing rates of
      immigration. Popular explanations of these trends include ageing populations,
      growing incomes, and feminisation of the health workforce. Although these
      explanations form part of the larger picture, analysis of the forces operating in
      the four countries suggests that specific policy measures largely unrelated to
      these factors have driven growing demand for health staff. On this basis we argue
      that specific policy measures are equally capable of reversing these trends and
      avoiding the exploitation of low-income countries' scarce resources. These
      policies should seek to ensure local stability in health labour markets so that
      shortages of staff are not solved via the international brain drain.

PMID- 16650655
TI  - Traffic fine.

PMID- 16650656
TI  - A Thai patient with generalised inflammatory skin disease 18 years after
      migration to Europe.

PMID- 16650657
TI  - Substance abuse treatment providers' beliefs and objections regarding contingency
      management: implications for dissemination.
AB  - Contingency management (CM) interventions are among the most effective methods
      for initiating drug abstinence, but they infrequently have been adopted by
      community drug and alcohol treatment programs. The primary purpose of this
      investigation was to determine the prevalence of specific beliefs that community
      treatment providers hold regarding contingency management interventions. We
      surveyed 383 treatment providers from three geographical areas of the United
      States regarding moral or ethical objections, negative side effects,
      practicality, limitations and positive opinions regarding tangible and social CM
      interventions. Results indicate that positive beliefs were surprisingly
      prevalent, with providers agreeing with an average of 67% of the positive
      statements regarding CM using tangible incentives and 54% indicating that they
      would be in favor of adding a tangible CM intervention to their treatment
      program. The most prevalent objections to incentive programs were that they cost
      too much, fail to address the underlying problems of addiction, and do not
      address multiple behaviors. Social incentives were viewed more favorably than
      tangible incentives and both were viewed more positively by providers who were
      supervisors, had advanced degrees, had more addictions experience, and had
      previous experience with tangible incentives. These findings have implications
      for improving the dissemination of this empirically-supported treatment.

PMID- 16650658
TI  - Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in
      abstained alcoholics.
AB  - Acute alcohol withdrawal is often associated with increased sympathetic activity,
      and a decreased baroreflex sensitivity (BRS) can be assumed. Parameters of heart
      rate variability (HRV), blood pressure variability (BPV), BRS as well as cardiac
      index (CI), left ventricular work index (LVWI) and total peripheral resistance
      (TPR) were investigated in 20 patients undergoing acute alcohol withdrawal and
      matched controls. Measures were obtained during the peak of withdrawal
      symptomatology prior to treatment as well as 2 and 24h under continuous
      clomethiazole treatment. Alcohol withdrawal scores were obtained and correlated
      with autonomic measures. In addition, parameters were assessed in 15 subjects who
      abstained from alcohol after long-term intake. We found a severe down-regulation
      of BRS during acute alcohol withdrawal and to a milder extent in abstained
      alcoholics. Furthermore, HRV and BPV did not unequivocally reveal signs of
      elevated sympathetic activity. Non-linear parameters of HRV and parameters of BRS
      correlated with the severity of AWS. The distinct decrease of BRS in AWS and in
      long-term abstained subjects described here is of importance since similar
      alterations have been identified as independent prognostic factors for cardiac
      mortality in other diseases.

PMID- 16650659
TI  - Detection of chlamydiae in boar semen and genital tracts.
AB  - Chlamydiae cause abortion and reproductive disorders in sows. Although organisms
      can infect the male genital tract, little is known about the disease situation in
      boars. Hence, we examined the prevalence of chlamydial infection in semen and
      genital tracts of boars. Samples collected from Swiss boars (group A: n=42), and
      boars from Germany (group B: n=39) were examined by bacteriology, LPS-ELISA,
      immunohistochemistry (IHC) and polymerase chain reaction (PCR). The latter
      methodology involved use of three PCR assays including 16Sig rDNA, IGS-S
      (intergenic spacer 16S/23S-Short) and IGS-L (intergenic spacer 16S/23S-Long) PCR
      for comparison methods. PCR sensitivity and the presence of potential PCR
      inhibitors were determined by spiking semen with Chlamydophila (Cp.) abortus DNA.
      Detection limits of the 16Sig and IGS-S PCR were 10 templates, while the IGS-L
      PCR was less sensitive (100 templates). Of 25 semen samples that were collected
      from group A, one semen sample was positive for Cp. psittaci and two were
      positive for Chlamydia-like organisms by 16Sig PCR. Screening of sera from Swiss
      boars revealed three animals with positive reactions in the LPS-ELISA, although
      we failed to detect chlamydiae within organs of these or sera-negative animals by
      IHC or IGS-S PCR. In group B, 10 ejaculates were positive for Chlamydia (C.) suis
      and two were positive for Chlamydia-like organisms by 16S PCR. The identification
      of DNA from Chlamydia-like organisms in semen from both groups of boars was
      surprising and a role for these bacteria in reproductive diseases requires
      further assessment. In conclusion, the prevalence of chlamydial infection was low
      in group A animals indicating that venereal transmission may not be significant
      for Chlamydia-associated reproductive diseases in pigs, although rare cases may
      occur.

PMID- 16650660
TI  - Evaluation of immune effects of fowlpox vaccine strains and field isolates.
AB  - The immune effects of fowlpox virus (FPV) field isolates and vaccine strains were
      evaluated in chickens infected at the age of 1 day and 6 weeks. The field
      isolates and the obsolete vaccine strain (FPV S) contained integrated
      reticuloendotheliosis virus (REV) provirus, while the current vaccine strain
      (FPVST) carries only REV LTR sequences. An indirect antibody ELISA was used to
      measure the FPV-specific antibody response. The non-specific humoral response was
      evaluated by injection of two T-cell-dependent antigens, sheep red blood cells
      (SRBC) and bovine serum albumin (BSA). There was no significant difference in the
      antibody response to FPV between chickens infected with FPV various isolates and
      strains at either age. In contrast, antibody responses to both SRBC and BSA were
      significantly lower in 1-day-old chickens inoculated with field isolates and FPV
      S at 2-3 weeks post-inoculation. Furthermore, cell-mediated immune (CMI)
      responses measured by in vitro lymphocyte proliferation assay and in vivo using a
      PHA-P skin test were significantly depressed in chickens inoculated with field
      isolates and FPV S at the same periods. In addition, thymus and bursal weights
      were lower in infected chickens. These immunosuppressive effects were not
      observed in chickens inoculated with the current vaccine strain, FPVST, at any
      time. The results of this study suggest that virulent field isolates and FPV S
      have immunosuppressive effects when inoculated into young chickens, which
      appeared in the first 3 weeks post infection. REV integrated in the FPV field
      isolates and FPV S may have played a central role in the development of
      immunosuppression.

PMID- 16650661
TI  - Clonal relationships among Clostridium perfringens of porcine origin as
      determined by multilocus sequence typing.
AB  - Clostridium perfringens is ubiquitous in the environment and the intestinal
      tracts of most mammals, but this organism also causes gas gangrene and enteritis
      in human and animal hosts. While expression of specific toxins correlates with
      specific disease in certain hosts, the other factors involved in commensalism and
      host pathogenesis have not been clearly identified. A multilocus sequence typing
      (MLST) scheme was developed for C. perfringens with the aim of grouping isolates
      with respect to disease presentation and/or host preference. Sequence data were
      obtained from one virulence and seven housekeeping genes for 132 C. perfringens
      isolates that comprised all five toxin types and were isolated from 10 host
      species. Eighty sequence types (STs) were identified, with the majority (75%)
      containing only one isolate. eBURST analysis identified three clonal complexes,
      which contained 59.1% of the isolates. Clonal complex (CC) 1 contained 31,
      predominantly type A isolates from diverse host species. Clonal complex 2
      contained 75% of the bovine type E isolates examined in this study. Clonal
      complex 3 consisted predominantly of porcine type A and type C isolates.
      Interestingly, these porcine isolates (n=32) all carried consensus cpb2 and cna
      genes, encoding beta2 toxin and CpCna, a collagen binding protein, respectively.
      This compares to carriage of both these genes by only 3.6% of porcine isolates
      not present in clonal complex 3 (n=28). The data obtained indicates that MLST may
      be used to identify host species relationships with respect to these C.
      perfringens isolates.

PMID- 16650662
TI  - Vertical transmission of a fluoroquinolone-resistant Escherichia coli within an
      integrated broiler operation.
AB  - The epidemiology of an enrofloxacin-resistant Escherichia coli clone was
      investigated during two separate outbreaks of colibacillosis in the Danish
      broiler production. In total five flocks were reported affected by the outbreaks.
      Recorded first-week mortalities were in the range of 1.7-12.7%. The clone was
      first isolated from dead broilers and subsequently demonstrated in samples from
      associated hatchers and the parent flock with its embryonated eggs, suggesting a
      vertical transmission from the parents. The second outbreak involved two broiler
      flocks unrelated to the affected flocks from the first outbreak. However, the
      clone could not be demonstrated in the associated parent flock. Furthermore,
      samplings from grand-parent flocks were negative for the outbreak clone. The
      clonality was evaluated by plasmid profiling and pulsed-field gel
      electrophoresis. None of the recognized virulence factors were demonstrated in
      the outbreak clone by microarray and PCR assay. The molecular background for the
      fluoroquinolone-resistance was investigated and point mutations in gyrA and parC
      leading to amino-acid substitutions in quinolone-resistance determining regions
      of GyrA and ParC were demonstrated. Vertical transmission of enrofloxacin
      resistant E. coli from healthy parents resulting in high first-week mortality in
      the offspring illustrates the potential of the emergence and spreading of
      fluoroquinolone-resistant bacteria in animal husbandry, even though the use of
      fluoroquinolones is restricted.

PMID- 16650663
TI  - Sample size for a clinical trial: why do some trials need only 100 patients and
      others 1000 patients or more?

PMID- 16650664
TI  - Population-based study of presbyopia in rural Tanzania.
AB  - OBJECTIVE: To determine the prevalence of presbyopia in a rural African
      population. DESIGN: Cross-sectional prevalence study. PARTICIPANTS: One thousand
      seven hundred nine persons age 40 years and older who resided in 3 villages and
      randomly selected neighborhoods of Kongwa town, Tanzania. METHODS: Eligible
      persons were refracted and given best distance correction. Near vision was tested
      and corrected to the nearest 0.5 diopter. Presbyopia was defined as at least 1
      line of improvement on a near visual acuity chart with an addition of a plus
      lens. RESULTS: A total of 61.7% of eligible participants were presbyopic. A
      higher prevalence of presbyopia was associated with increased age, female gender,
      higher educational level, and residence in town (odds ratio = 3.09; 95%
      confidence interval: 2.46-3.90). The odds of developing presbyopia increased 16%
      per year of age from age 40 to 50, but the increase was nonsignificant at 1% per
      year after age 50. More severe presbyopia was associated with female gender and
      less with education. CONCLUSIONS: This study provides the first population-based
      data on prevalence of presbyopia in a large, random sample of older Africans and
      suggests a high rate of presbyopia. Presbyopia plateaus after age 50, and it is
      more common in females. In addition, the 3-fold increased odds in town versus
      village dwellers was unexpected and suggests that research of other factors,
      including environmental factors, is warranted.

PMID- 16650665
TI  - Impact of presbyopia on quality of life in a rural African setting.
AB  - PURPOSE: To determine the impact of uncorrected presbyopia on quality of life in
      rural Tanzania. DESIGN: Cross-sectional study. PARTICIPANTS: Population-based
      sample of 1709 village and town-dwelling adults aged 40 and older in the Kongwa
      district in rural Tanzania. METHODS: Subjects underwent distance and near visual
      acuity testing to determine presbyopia. A near vision-related quality of life
      questionnaire was administered by trained interviewers to determine the degree of
      self-rated difficulty with tasks appropriate to life in a rural African setting,
      and how much near vision loss contributed to this difficulty. MAIN OUTCOME
      MEASURES: Near vision-related quality of life. RESULTS: Complete data were
      available for 1564 (92%) of the subjects. The prevalence rate of presbyopia was
      62%. The majority of presbyopes (94%) did not have corrective near vision
      glasses. Compared with nonpresbyopes, being presbyopic increased the odds of
      reporting some difficulty with near vision tasks by 2-fold (odds ratio [OR],
      2.04; 95% confidence interval [CI]: 1.57-2.66), odds of reporting moderate
      difficulty by 5-fold (OR 5.01; 95% CI: 3.19-7.89), and odds of reporting high
      difficulty by >8-fold (OR 8.52; 95% CI 3.13-23.10). The degree of presbyopia was
      associated with increasing difficulty with daily tasks (P<0.0001). CONCLUSIONS:
      This is the first study to demonstrate that uncorrected presbyopia has a
      significant impact on vision-related quality of life in a rural African setting.
      The high prevalence of presbyopia, and increased aging of the population in
      developing countries, suggests that the World Health Organization's Vision 2020
      refraction agenda should place greater emphasis on presbyopia.

PMID- 16650666
TI  - Evidence for delayed presbyopia after photorefractive keratectomy for myopia.
AB  - PURPOSE: To evaluate uncorrected near visual acuity (NVA), accommodation, corneal
      aberrations, and the optical quality of the retinal image in presbyopic eyes
      after photorefractive keratectomy (PRK). DESIGN: Nonrandomized comparative
      retrospective study. PARTICIPANTS: Ten post-PRK patients and 10 normal patients.
      METHODS: Twenty eyes (10 right and 10 left after PRK for myopia, minimum of 10
      years after the operation; group A) were compared with 20 eyes (10 right and 10
      left age- and gender-matched normal controls; group B). All subjects were over 40
      years of age. MAIN OUTCOME MEASURES: With best distance correction, NVA was
      measured at 40 cm (Jaeger, J series), and the range of accommodation (diopters
      [D]) was measured subjectively (negative relative amplitude and positive relative
      amplitude). The modulation transfer function (MTF) and corneal aberrations such
      as comalike, spherical (SAs), and higher order (HOAs) were measured with a
      Hartmann-Shack aberrometer. From the MTF curves, the spatial frequencies
      corresponding to contrast values of 0.1 and 0.5 were noted. RESULTS: Mean ages
      (+/- standard deviations [SDs]) were 46.3 years (4.7) for group A and 47.6 years
      (4.9) for group B (P>0.05). Near acuity was J1 or better in 12 of 20 post-PRK and
      4 of 20 control eyes. Mean accommodations (+/- SDs) were 3.2 D (1.14) for right
      group A eyes and 2.1 D (0.94) for right group B eyes (P = 0.0152), and 3.4 D
      (0.99) for left A eyes and 2.3 D (1.02) for left B eyes (P = 0.0168). Total HOA
      indexes (+/- SDs) were 1.449 (0.409) for right group A eyes and 0.824 (0.241) for
      right group B eyes (P = 0.008), and 1.464 (0.388) for left A eyes and 1.067
      (0.542) for left B eyes (P = 0.0752). Pooling the data from post-PRK and control
      eyes, a significant correlation was found between near acuity and SA (right eyes,
      r = -0.535, P = 0.015; left eyes, r = -0.493, P = 0.027). Significant
      associations were found between accommodation, near acuity, HOA, and comalike
      aberration for right eyes only. Mean spatial frequencies (+/- SDs) corresponding
      to contrast values of 0.1 for right and left eyes were 14.96 (5.71) for right
      group A eyes and 22.02 (6.85) for right group B eyes (P = 0.074), and 15.11
      (7.80) for left A eyes and 21.41 (9.00) for left B eyes (P = 0.271). Mean spatial
      frequencies (+/- SDs) corresponding to contrast values of 0.5 for right and left
      eyes were 2.86 (0.63) for right group A eyes and 3.21 (0.35) for right group B
      eyes (P = 0.596), and 2.76 (0.98) for left A eyes and 3.22 (0.27) for left B eyes
      (P = 0.194). CONCLUSIONS: Compared with normal eyes, in previously myopic eyes
      treated with first-generation PRK lasers there is a tendency for (1) the optical
      quality of the retinal image to be reduced at low contrast, (2) the aberrations
      attributed to the corneal surface to increase, and (3) both measured subjective
      accommodation and near acuity to be greater than expected. We postulate that the
      corneal aberrations induced by PRK for myopia may reduce the quality of the
      retinal image for distance but enhance near acuity by way of a multifocal effect
      that can delay the onset of age-related near vision symptoms.

PMID- 16650667
TI  - Corneal ectasia after photorefractive keratectomy for low myopia.
AB  - OBJECTIVE: To alert ophthalmologists of the possibility of an aggravation of
      forme fruste keratoconus after photorefractive keratectomy (PRK). DESIGN:
      Clinical case report. INTERVENTION: Standard bilateral PRK for low myopia. MAIN
      OUTCOME MEASURES: Corneal topography, corneal thickness, and visual acuity.
      RESULTS: Corneal ectasia occurred bilaterally after PRK. Retrospective analysis
      of preoperative videokeratography indicated the existence of forme fruste
      keratoconus on the left eye. CONCLUSIONS: This article is the first case report
      of a bilateral corneal ectasia after PRK for low myopia. Even if there is no
      direct proof to demonstrate that PRK has worsened the evolution of keratoconus,
      the safety of the PRK procedure in forme fruste keratoconus must be considered.

PMID- 16650668
TI  - Prevalence and risk factors of lens opacities in urban and rural Chinese in
      Beijing.
AB  - OBJECTIVE: To determine the prevalence of lens opacities in the elderly Chinese
      population in an urban and a rural region of Beijing. DESIGN: Population-based
      cross-sectional study. PARTICIPANTS: The study included 4439 subjects of 5324
      subjects invited to participate (response rate, 83.4%). The subjects were divided
      into a rural part (1973 subjects [44.4%]) and an urban part (2466 subjects
      [55.6%]). The study was limited to participants age 40 and older, and the mean
      age was 56.2+/-10.6 years (range, 40-101 years). METHODS: Nuclear, cortical, and
      posterior subcapsular lens opacities were assessed based on standardized slit
      lamp photographs of the lens using a modification of the grading score of the Age
      related Eye Disease Study (AREDS). MAIN OUTCOME MEASURES: Grading score of the
      AREDS. RESULTS: Lens data were provided for 4378 subjects (98.6%) of 4439 persons
      examined, which consisted of 8724 eyes. Prevalence of any cataract surgery was
      1.3% (95% confidence interval [CI]: 1.0-1.7), which was statistically independent
      of gender (P = 0.51; odds ratio [OR]: 0.86; 95% CI: 1.00-1.34), rural area versus
      urban region (P = 0.25), and level of education (P = 0.84). Prevalence of any
      nuclear lens opacity was 82.0% (95% CI: 80.8-83.2); prevalence of any cortical
      lens opacity was 10.3% (95% CI: 9.4-11.3); and prevalence of any posterior
      subcapsular opacity was 4.3% (95% CI: 3.7-4.9). If grade 2 of nuclear lens
      opacity was considered to be normal, prevalence of nuclear cataract was 50.3%
      (95% CI: 48.8-51.8), and the overall prevalence of any cataract was 53.1% (95%
      CI: 51.6-54.6), increasing from 6.5% (95% CI: 5.2-7.8) in those subjects 40 to 49
      years of age to 52.3% (95% CI: 47.4-55.3) in those who were 50 to 59 years of
      age, and to 97.8% (95% CI: 96.4-99.2) in those 70 years and older (P<0.001).
      Frequencies of any cortical cataract and any subcapsular posterior cataract were
      10.3% (95% CI: 9.4-11.3) and 4.3% (95% CI: 3.7-4.9), respectively. CONCLUSIONS:
      Cataracts are common among adult Chinese residents in Beijing, with age as the
      most important associated factor. In view of the relatively low rate of cataract
      surgery performed so far, one may expect a marked increase in the number of
      cataract surgeries to meet the visual needs of the growing elderly population in
      China.

PMID- 16650669
TI  - Subconjunctival sodium hyaluronate 2.3% in trabeculectomy: a prospective
      randomized clinical trial.
AB  - PURPOSE: To investigate the efficacy of subconjunctival sodium hyaluronate 2.3%
      in increasing the success rate of glaucoma filtering surgery and promoting
      filtering blebs with characteristics presumed to predict better success. DESIGN:
      Randomized controlled clinical trial. PARTICIPANTS: Fifty-five patients scheduled
      for glaucoma surgery. INTERVENTION: Patients underwent routine trabeculectomy,
      with or without phacoemulsification and intraocular lens implantation. In the
      study group (n = 28), sodium hyaluronate 2.3% was injected between the scleral
      and conjunctival flaps at the conclusion of the surgery. In the control group (n
      = 27), balanced salt solution (BSS) was injected in the same fashion, in an
      unmasked design. MAIN OUTCOMES MEASURES: Surgical success was defined as (1) a
      complete success if the intraocular pressure (IOP) was 21 mmHg or less without
      any antiglaucoma medication, and (2) a qualified success if the IOP was 21 mmHg
      or less, with or without antiglaucoma medication. Patients requiring additional
      surgery, including needling, or with IOP more than 21 mmHg, even when receiving
      antiglaucoma medications, were considered to have failed treatment. Success rates
      in both groups were compared using Kaplan-Meier survival curves and the log-rank
      test. The morphologic characteristics of the filtering blebs were evaluated using
      the Indiana Bleb Appearance Grading Scale. Other outcome measures were IOP,
      visual acuity, need for antiglaucoma medication, and any complications. RESULTS:
      Fifty-two patients completed the study (27 in the study group and 25 in the
      control group), with a mean follow-up of 12.3 months. Complete success rates were
      77.8% for the study group and 84.0% for the control group 12 months after surgery
      (P>0.5); qualified success rates were 88.9% for the study group and 92.0% for the
      control group (P>0.6). Mean IOP decreased from 26.0+/-10.0 mmHg to 11.6+/-4.1
      mmHg in the study eyes (P<0.001) and from 24.9+/-9.7 mmHg to 13.0+/-4.1 mmHg in
      the control eyes (P<0.001). Intraocular pressure measurements in both groups were
      similar at all visits (P>0.05). The study eyes had more diffuse blebs than the
      control eyes (62.5% > or =4 clock-hours vs. 22.7%; P = 0.012). Postoperative
      complications were similar in the study eyes (14.8%) and the control eyes (20.0%;
      P>0.6). CONCLUSIONS: There was no difference in success rates in patients who
      received subconjunctival sodium hyaluronate 2.3% compared to BSS injections.
      Subconjunctival sodium hyaluronate 2.3% was associated with more diffuse blebs
      after filtering surgery.

PMID- 16650670
TI  - 24-hour intraocular pressure control with maximum medical therapy compared with
      surgery in patients with advanced open-angle glaucoma.
AB  - PURPOSE: The purpose of this study was to evaluate 24-hour intraocular pressure
      (IOP) control in patients with moderate to severe open-angle glaucoma treated by
      trabeculectomy and mitomycin C versus maximum tolerated medical therapy. DESIGN:
      Prospective observational study. PARTICIPANTS: Thirty surgical patients and 30
      medically treated patients with advanced glaucoma. METHODS: Patients successfully
      treated with initial trabeculectomy or patients considered successfully treated
      on maximum tolerated medical therapy (2-4 medicines) were enrolled. We performed
      IOP measurements at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am. Patients were
      matched by IOP +/- 1 mmHg at 10 am. MAIN OUTCOME MEASURES: A 24-hour IOP control.
      RESULTS: The surgical patients had a mean diurnal IOP of 12.1+/-2.2 versus 13.5+/
      2.0 mmHg for the matched medically treated patients (P = 0.0001). The average
      maximum IOP for the surgical group was 13.4+/-2.3 and 16.3+/-3.2 mm Hg for the
      medical group (P<0.0001). The 24-hour range of IOP for the surgical group was
      2.3+/-0.8 and 4.8+/-2.3 mmHg for the medical group (P<0.0001). Except at 10 am (P
      = 0.5), the surgical group had a statistically lower IOP at each measured time
      point. Eleven (37%) patients in the medically treated group, and none in the
      surgically treated group, had peak IOPs > or = 18 mmHg. The majority of peak IOPs
      (10 of 11) occurred outside of normal office hours. CONCLUSIONS: This study
      suggests that a well-functioning trabeculectomy provides a statistically lower
      mean, peak, and range of IOP for the 24-hour day than maximum tolerated medical
      therapy in advanced glaucoma patients.

PMID- 16650671
TI  - Clinical experience with the Baerveldt 250-mm2 Glaucoma Implant.
AB  - PURPOSE: To report the intermediate-term results of the Baerveldt 250-mm2
      Glaucoma Implant for treatment of adult glaucoma. DESIGN: Retrospective,
      noncomparative, interventional case series. PARTICIPANTS: One hundred eight adult
      patients (108 eyes) with glaucoma who received a Baerveldt 250-mm2 Glaucoma
      Implant. INTERVENTION: Implantation of the Baerveldt 250-mm2 Glaucoma Implant.
      MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual acuity, number of
      glaucoma medications, and surgical complications. Success was defined as IOP > or
      = 6 mmHg and < or = 21 mmHg (with or without antiglaucoma medications), without
      further glaucoma surgery, devastating complication, or loss of light perception
      attributable to drainage implantation. RESULTS: Mean age was 63.8+/-16.5 years.
      Mean postoperative follow-up was 22.8 months (range, 0.2-84.9; interquartile
      range, 3.9-36.3). Mean preoperative IOP was 36.3+/-13.0 mmHg, on 2.9+/-1.1
      antiglaucoma medications. The mean postoperative IOP at final visit was 15.8+/
      7.6 mmHg (P<0.0001, paired t test), on 0.8+/-1.0 antiglaucoma medications
      (P<0.0001, Wilcoxon test). Kaplan-Meier success rates were 0.92 (6 months, n =
      81), 0.88 (12 months, n = 75), 0.84 (18 months, n = 68), and 0.79 (24 months, n =
      61). CONCLUSIONS: The Baerveldt 250-mm2 Glaucoma Implant provides good
      intermediate-term success for the treatment of adult refractory glaucoma.

PMID- 16650672
TI  - Peripapillary retinal nerve fiber layer thickness variations with myopia.
AB  - PURPOSE: To determine the relationship between peripapillary retinal nerve fiber
      layer (RNFL) thickness and myopia using optical coherence tomography (OCT).
      DESIGN: Prospective observational case series. METHODS: One hundred thirty-two
      young males with myopia (spherical equivalent [SE], -0.50 to -14.25 diopters)
      underwent ophthalmic examination of one randomly selected eye. Optical coherence
      tomography (OCT-1, version 4.1) was performed by a single operator using circular
      scans concentric with the optic disc with scan diameters of 3.40 mm, 4.50 mm, and
      1.75 x vertical disc diameter (VDD). For each scan diameter, mean peripapillary
      RNFL thickness was calculated. Statistical analysis comprised repeated
      measurements analysis and Pearson correlation. RESULTS: Mean peripapillary RNFL
      thickness did not correlate with SE for the 3.40-mm (r = -0.11, P = 0.22), 4.50
      mm (r = -0.103, P = 0.24), or 1.75xVDD (r = -0.08, P = 0.36) OCT scan diameters.
      Neither did mean peripapillary RNFL thickness correlate with axial length for the
      3.40-mm (r = -0.04, P = 0.62), 4.50-mm (r = 0.03, P=0.75), or 1.75xVDD (r = 
      0.02, P = 0.78) scan diameters. Mean peripapillary RNFL thicknesses for the 3.40
      mm, 4.50-mm, and 1.75xVDD scans were 101.1+/-8.2 microm (95% confidence interval
      [CI], 99.4-102.8), 78.9+/-8.2 microm (95% CI, 77.5-80.3), and 97.5+/-10.9 microm
      (95% CI, 95.6-99.4), respectively. CONCLUSIONS: Mean peripapillary RNFL thickness
      did not vary with myopic SE or axial length for any OCT scan diameter
      investigated. Retinal NFL thickness measurements may be a useful parameter to
      assess and monitor glaucoma damage in myopic subjects.

PMID- 16650673
TI  - Specificity of the Heidelberg Retina Tomograph's diagnostic algorithms in a
      normal elderly population: the Bridlington Eye Assessment Project.
AB  - PURPOSE: To determine the specificity of the Moorfields regression analysis (MRA)
      and R. Burk (RB) and F. S. Mikelberg (FSM) linear discriminant functions (LDFs)
      in classifying the optic discs of normal elderly patients imaged with the
      Heidelberg Retina Tomograph. DESIGN: Cross-sectional study. PARTICIPANTS: Optic
      nerve head analysis of 459 eyes of 459 normal elderly patients was performed by 2
      operators. All patients were consecutive in a cohort screened for eye disease.
      Normals were defined as having a normal visual field (VF) on automated
      suprathreshold screening, normal intraocular pressure, and normal visual acuity.
      MAIN OUTCOME MEASURES: Specificity of the optic nerve head classification by MRA
      and the RB and FSM LDFs. RESULTS: Subjects' mean age (262 female, 197 male) was
      72.6 years. Males were found to have significantly larger cups than females.
      Eighty-three percent, 11.3%, and 5.7% of discs were classed as within normal
      limits, borderline, and outside normal limits by MRA. Percentages of optic discs
      classified as outside normal limits in the smallest and largest quartiles for
      disc size were 0.9% and 14.9%. The association of disc size with the
      classification of outside normal limits was significant in males only. Agreement
      in MRA classification between 2 investigators separately placing the optic disc
      contour was moderate (Cohen's kappa = 0.54, P<0.001). The RB and FSM LDFs
      classified 6.8% and 11.8% of discs as diseased. The RB LDF was significantly more
      likely to return a diagnosis of disease in larger discs, though only in males.
      The FSM LDF tended to the same drop in specificity, although not significantly.
      CONCLUSIONS: Using the MRA and RB/FSM LDFs, specificity fell dramatically with
      increasing disc size, particularly in males. This may reflect the finding of
      significantly larger cups in males than in females in the normal elderly
      population. This divergence was not predicted by these diagnostic functions,
      which were developed on samples of younger subjects.

PMID- 16650674
TI  - Retinal nerve fiber layer thickness in normal children measured with optical
      coherence tomography.
AB  - PURPOSE: To measure the peripapillary retinal nerve fiber layer (RNFL) thickness
      in normal children. DESIGN: Observational cross-sectional study. PARTICIPANTS:
      Ninety-two eyes of 92 normal children ages 4 to 17 years presenting to the
      Ophthalmology Clinic at the Harkness Eye Institute, Department of Ophthalmology,
      Columbia University. METHODS: Retinal nerve fiber layer thickness was measured
      with optical coherence tomography (OCT). Patient cooperation and signal strength
      of the OCT scans were assessed. Optic disc photographs were evaluated by a
      glaucoma specialist in a masked fashion. Eyes with abnormal optic discs were
      excluded. One eye of each subject was randomly selected for statistical analysis.
      The effect of several factors on RNFL thickness was investigated statistically.
      MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness. RESULTS: Ninety-one
      percent of the study subjects were Hispanic; 8%, African American; and 1%,
      Caucasian. Optical coherence tomography measurements were obtained in 117 of 121
      (96.7%) subjects, and disc photographs were available for 92 of them. Mean age
      (+/-standard deviation [SD]) was 9.7+/-2.7 years. Mean global RNFL thickness (+/
      SD) was 107.0+/-11.1 microm (range, 78.1-134.6). The RNFL was thickest inferiorly
      (136.9+/-16.9 microm) and superiorly (135.4+/-19.3 microm), thinner nasally
      (83.0+/-18.0 microm), and thinnest temporally (72.5+/-13.4 microm). In univariate
      regression analysis, age (P = 0.013) and refraction (P<0.001) had a significant
      effect on RNFL thickness; age had a significant effect on refraction (P<0.001).
      When controlling for refraction, age no longer had a significant effect.
      CONCLUSIONS: Optical coherence tomography can be used to measure RNFL thickness
      in children. Refraction had an effect on RNFL thickness. In normal children,
      variation in RNFL thickness is large. The normative data provided by this study
      may assist in identifying changes in RNFL thickness in children.

PMID- 16650675
TI  - Corneal pachymetry mapping with high-speed optical coherence tomography.
AB  - OBJECTIVE: To map corneal thickness before and after LASIK with optical coherence
      tomography (OCT). DESIGN: Cross-sectional observational study. PARTICIPANTS:
      Forty-two eyes of 21 normal subjects undergoing LASIK. METHODS: A high-speed
      (2000 axial scans/second) 1.3-microm-wavelength corneal and anterior segment OCT
      prototype was used for corneal scanning. The scan pattern consisted of 10-mm
      radial lines on 8 meridians centered on the vertex reflection. The entire scan
      pattern of 1024 a-scans was acquired in 0.5 seconds. We developed automated
      computer processing for 3-dimensional corneal reconstruction and measurement.
      Corneal thickness was measured normal to the anterior surface and presented as
      color pachymetry maps and zonal statistics. The maps were divided into a central
      zone (<2 mm) and 3 annular areas (pericentral, 2-5 mm; transitional, 5-7 mm;
      peripheral, 7-10 mm), which were further divided into quadrantal zones. The
      average, minimum, and maximum corneal thicknesses were computed for zones within
      the 7-mm diameter. Optical coherence tomography and ultrasound pachymetry were
      measured 3 times at the preoperative and 3-month postoperative visits.
      Reproducibility was assessed by the pooled standard deviations (SDs) of the
      repeated measurements. MAIN OUTCOME MEASURES: Optical coherence tomography
      pachymetric map and zonal statistic, and ultrasound pachymetry. RESULTS: Before
      LASIK, central corneal thicknesses (CCTs) were 546.9+/-29.4 microm (mean +/- SD)
      for OCT and 553.3+/-33.0 microm for ultrasound. After LASIK, CCTs were 513.7+/
      44.5 microm for OCT and 498+/-46.6 microm for ultrasound. Optical coherence
      tomography and ultrasound CCT were highly correlated (Pearson correlation r =
      0.97 before LASIK and 0.98 afterwards). Optical coherence tomography CCT was
      slightly less than ultrasound CCT before surgery (mean difference, -6.4 microm;
      95% limits of agreement, -23.2 to 10.4 microm) but slightly greater after LASIK
      (15.7 microm; -1.6 to 33 microm). These differences were statistically
      significant, but no more than the CCT measurement differences between ultrasound
      pachymeters. The reproducibility of the OCT zonal pachymetry averages was roughly
      2 microm. CONCLUSIONS: High-speed OCT provided noncontact, rapid, reproducible
      pachymetric mapping over a wide area of the cornea. It is equivalent to
      ultrasound for CCT measurement before and after LASIK. This technology could be
      valuable for planning keratorefractive procedures and diagnosis of corneal
      diseases.

PMID- 16650676
TI  - Central serous chorioretinopathy after solid organ transplantation.
AB  - PURPOSE: To describe the demographic and clinical characteristics of central
      serous chorioretinopathy (CSC) after solid organ transplantation. DESIGN: Case
      series. PARTICIPANTS: Fifteen patients who presented to the authors with CSC
      after solid organ transplantation. METHODS: We performed a retrospective chart
      review to identify patient demographics and clinical features of disease,
      including angiographic changes. MAIN OUTCOME MEASURES: Patterns of CSC. These
      patterns were compared with type of organ received, demographics, and visual
      outcome. RESULTS: We identified 25 eyes of 7 women (46.7%) and 8 men (53.3%) that
      developed CSC after solid organ transplantation. Patient ages ranged from 27 to
      55 years (median, 40). Seven of the 15 patients (46.7%) were Caucasian, including
      3 Hispanic patients (20%). Of the 8 remaining patients (53.3%), 2 were African
      American (13.3%), 2 were Filipino (13.3%), and 4 were Asian (26.7%). The organs
      received included 13 kidneys (86.7%), 1 liver (6.7%), and 1 heart (6.7%).
      Systemic hypertension was reported in 14 of 15 patients (93.3%). All patients
      were receiving systemic immunosuppressive drugs at presentation; 14 of 15 (93.3%)
      were also receiving systemic corticosteroids. Visual acuity at presentation
      ranged from 20/20 to counting fingers. Patterns of CSC included (1) geographic or
      diffuse alterations in the retinal pigment epithelium (5 eyes; 2 bilateral, 1
      unilateral), (2) focal CSC (6 eyes, all unilateral), (3) multifocal CSC (6 eyes;
      2 bilateral, 2 unilateral), and (4) CSC with bullous retinal detachment (8 eyes,
      all bilateral). Follow-up, available for 21 affected eyes of 13 patients, ranged
      from 1 month to 6 years (median, 12 months). Compared with other solid organ
      transplant recipients at our institutions, renal transplant recipients (P =
      0.003), as well as Hispanic and Asian patients (P = 0.05), were more prevalent in
      this cohort. CONCLUSION: Central serous chorioretinopathy after solid organ
      transplantation varies in presentation and severity. Our observations support a
      role for choroidal vascular compromise in the pathogenesis of this disorder.

PMID- 16650677
TI  - Fundus autofluorescence in patients with pseudoxanthoma elasticum.
AB  - PURPOSE: To evaluate the autofluorescence findings of patients with
      pseudoxanthoma elasticum, a disease resulting from a defect in a reputed
      transport protein encoded by the gene adenosine triphosphate-binding cassette
      subtype C number 6. DESIGN: Observational case series. METHODS: Color, red-free
      monochromatic, and autofluorescence photography and fluorescein angiography of
      patients with pseudoxanthoma elasticum seen in a referral practice were
      evaluated. MAIN OUTCOME MEASURES: Cataloging of the abnormalities as detected by
      autofluorescence photography. RESULTS: The 8 subjects ranged in age from 26 to 60
      years (mean, 55+/-12), and their best-corrected visual acuity ranged from 20/20
      to 5/400 (mean, 20/50). Of the 16 eyes of the 8 patients, all had abnormalities
      typical of pseudoxanthoma elasticum, including angioid streaks in 14, peau
      d'orange in 4, and choroidal neovascularization in 11. Angioid streaks appeared
      as hypoautofluorescent fissures, sometimes showing expansion of the
      hypoautofluorescence suggestive of retinal pigment epithelium (RPE) absence or
      atrophy. Peau d'orange had a stippled appearance of autofluorescence, and drusen
      of the optic nerve appeared as hyperautofluorescent bodies. In addition to the
      expansion of RPE atrophy around angioid streaks, 3 additional configurations of
      RPE atrophy were recognized as RPE rips in 6 eyes, multilobular areas of atrophy
      in 9 eyes, and broad areas of poorly demarcated atrophy in 5 eyes. Some eyes had
      more than one manifestation of RPE atrophy, but the latter 3 types of atrophy
      occurred in eyes with, but not necessary contiguous to, concurrent choroidal
      neovascularization. CONCLUSIONS: Autofluorescence photography demonstrated that
      patients with pseudoxanthoma elasticum have more widespread areas of RPE
      disturbance, particularly atrophy, than what is detectable by other means of
      ocular imaging, which suggests that the RPE disturbance may play a role in the
      pathogenesis of visual loss in patients with pseudoxanthoma elasticum.

PMID- 16650678
TI  - Scleral buckling procedures for longstanding or chronic rhegmatogenous retinal
      detachment with subretinal proliferation.
AB  - OBJECTIVE: To investigate longstanding or chronic retinal detachments (RDs) with
      subretinal strands and their clinical features and therapeutic effects using
      conventional retinal surgery. DESIGN: Retrospective, consecutive, noncomparative
      case series. PARTICIPANTS: Cases of 36 patients (40 eyes) with longstanding RD
      and subretinal proliferation who had undergone scleral buckling or encircling
      procedures between January 1, 1995 and October 31, 2003 at one institution were
      reviewed. METHODS: A retrospective analysis of the patient data was conducted
      from the medical records. MAIN OUTCOME MEASURES: Visual acuity (VA) and
      postoperative anatomic retinal reattachment at the final follow-up visit between
      3 and 24 months (mean, 6.9). RESULTS: Forty eyes with an RD (mean duration, 13.8
      months) treated with scleral encircling and buckling had a 90% cure rate after
      one surgery. The VA levels increased in 77.5% of eyes to over 5/100 at the final
      follow-up visit. Longstanding or chronic RD with subretinal proliferation had
      subretinal proliferative strands (i.e., a shallow RD) and a smooth atrophic
      detached retina, not a thickened retina. CONCLUSIONS: Our results suggest that
      scleral encircling and buckling can be used in most patients with a longstanding
      RD. The chronic pathologic course of longstanding rhegmatogenous RD should be
      considered before treatment.

PMID- 16650679
TI  - Interobserver agreement in the interpretation of single-field digital fundus
      images for diabetic retinopathy screening.
AB  - PURPOSE: To assess agreement among a group of ophthalmic care providers,
      including ophthalmologists and trained nonphysician personnel, in the
      interpretation of single-field digital fundus images for diabetic retinopathy
      screening. DESIGN: Interobserver reliability study. PARTICIPANTS: Twelve
      ophthalmic care personnel, including 3 retina specialists, 3 general
      ophthalmologists, 3 ophthalmic nurses, and 3 ophthalmic photographers. METHODS:
      All participants were to read 400 good single-field digital fundus images of
      diabetic patients from a community hospital. The nonphysician personnel group
      read the images 1 month after attending a 2-day intensive instruction course
      regarding diabetic retinopathy screening. The ophthalmologists read the images
      without additional training. The 3 retina specialists read the images again
      together 2 months later to form a consensus regarding retinopathy severity and
      macular edema for each case. All readers used the Early Treatment Diabetic
      Retinopathy Study standard photographs as guidelines. MAIN OUTCOME MEASURES: The
      kappa statistic was used for the reliability assessment of the diabetic
      retinopathy severity and macular edema, and for the identification of cases that
      needed referral to ophthalmologists. RESULTS: There is only fair agreement among
      all readers. The multirater kappa coefficient for retinopathy severity is 0.34;
      for macular edema, 0.27; and for referral cases, 0.28. Retina specialists have
      the best agreement among all groups (kappa = 0.58 for retinopathy severity or
      macular edema, kappa = 0.63 for referrals). There is also fair agreement when all
      readers are compared with the consensus of retina specialists (kappas = 0.35,
      0.28, and 0.29 for retinopathy severity, macular edema, and referrals,
      respectively), and the retina specialist group also has the best agreement
      (kappas = 0.63, 0.65, and 0.67 for retinopathy severity, macular edema, and
      referrals). CONCLUSIONS: Without additional training, retina specialists may be
      the most reliable personnel to interpret single-field digital fundus images for
      diabetic retinopathy screening. For other ophthalmic care personnel to achieve
      comparable reliability, a comprehensive instruction course with specific
      continuing education is essential. Authorized nonphysician interpreters should be
      experts, and new standard photographs for single-field digital fundus image
      interpretation may also be required to improve interobserver reliability.

PMID- 16650680
TI  - Comparison of nonmydriatic digital retinal imaging versus dilated ophthalmic
      examination for nondiabetic eye disease in persons with diabetes.
AB  - OBJECTIVE: To evaluate the ability of stereoscopic nonmydriatic digital retinal
      imaging to detect ocular pathologic features other than diabetic retinopathy (DR)
      in patients with diabetes mellitus (DM) compared with dilated retinal examination
      by retinal specialist ophthalmologists. DESIGN: Clinic-based comparative
      instrument study and retrospective chart review. PARTICIPANTS: Two hundred eighty
      Joslin Diabetes Center outpatients (560 eyes) with type 1 or type 2 DM. METHODS:
      Nonsimultaneous stereoscopic nonmydriatic digital retinal images (640 x 480
      pixels) of three 45 degrees retinal fields were acquired and graded for clinical
      level of DR and other ocular pathologic features by certified readers according
      to Joslin Vision Network (JVN) protocol. Retrospective chart review compared
      findings from JVN digital images with findings from dilated retinal examination
      by retinal specialists performed within an average of 39.6 days of digital
      imaging. An independent senior retinal specialist adjudicated disagreements by
      review of 7 standard field 35-mm Early Treatment Diabetic Retinopathy Study
      protocol fundus photographs and JVN images. MAIN OUTCOME MEASURES: Detection of
      non-DR ocular pathologic features by digital imaging as compared with clinical
      examination. RESULTS: Nonmydriatic digital evaluation identified at least 1 non
      DR ocular finding in 40.7% of patients (114/280). Non-diabetes mellitus ocular
      pathologic features identified by digital images, clinical examination, or both
      included cataract (n = 100); age-related maculopathy (n = 52); suspicion of
      glaucoma (n = 18); choroidal lesions (n = 18); evidence of systemic disorder
      (e.g., hypertension or renal disease; n = 15); epiretinal membrane (n = 11);
      chorioretinal atrophy, scar, or both (n = 6); retinal emboli (n = 3); retinitis
      pigmentosa (n = 1); and asteroid hyalosis (n = 1). Agreement of nonmydriatic
      imaging with clinical examination for presence and absence of these findings was
      95.4%, 91.3%, 98.2%, 98.6%, 98.2%, 99.6%, 100%, 100%, 100%, and 100%,
      respectively. Kappa values for all non-DR lesions demonstrated near perfect
      agreement (kappa> or =0.80) except for age-related maculopathy (kappa = 0.71) and
      choroidal lesions (kappa = 0.73), where agreement was substantial. Overall, only
      55 eyes (9.8%) were ungradable for level of DR and 85 eyes (15.2%) were
      ungradable for macular edema. CONCLUSIONS: Joslin Vision Network nonmydriatic
      digital imaging demonstrated excellent agreement with dilated ophthalmic
      examination by retinal specialists in the detection of ocular disease other than
      DR, suggesting a potential role for this technology in evaluating non-DR
      disorders and highlighting the extent of findings other than retinopathy in
      patients with diabetes.

PMID- 16650681
TI  - Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological
      assessment of visual function.
AB  - PURPOSE: To evaluate retinal function in subjects suffering from hypotrichosis
      with juvenile macular dystrophy (HJMD). DESIGN: Retrospective case-control study.
      PARTICIPANTS: Sixteen HJMD patients belonging to 2 genetic groups and 20 control
      subjects. METHODS: The HJMD patients underwent clinical ophthalmological
      examination and electrophysiological testing for a period of as many as 14 years.
      The electroretinogram (ERG), electro-oculogram (EOG), and visual evoked potential
      (VEP) were recorded serially to assess visual function and to follow possible
      progression of the disease. MAIN OUTCOME MEASURES: Amplitudes and implicit times
      of ERG and VEP, and Arden ratio of EOG. RESULTS: Fundus examination revealed
      pigmentary abnormalities with atrophic changes at the posterior pole extending to
      regions beyond the macular area. A slow and time-dependent decline in visual
      acuity was noted. The ERG responses were subnormal in amplitude. The ERG deficit
      was similar for light- and dark-adapted responses. There was a gradual but
      consistent decrease in the ERGs with time. The EOG measurements were within the
      normal range. Pattern reversal VEPs were very subnormal, even in patients with
      mild deterioration of visual acuity. The flash VEPs were of slightly subnormal
      amplitudes and implicit times in the upper limit of the normal range.
      CONCLUSIONS: The fundus pictures and electrophysiological tests were consistent
      with retinal involvement extending beyond the macular region. Follow-up of visual
      acuity and ERG testing indicated a slowly progressing retinal disorder affecting
      cone-mediated vision as well as rod-mediated vision. Therefore, we suggest that a
      more appropriate name for this syndrome is hypotrichosis with cone-rod dystrophy.

PMID- 16650682
TI  - Vitreous hemorrhage in children.
AB  - PURPOSE: To describe the presentations, etiologies, and visual outcomes of
      spontaneous and traumatic vitreous hemorrhage in children. DESIGN: Retrospective
      case series of patients seen over 8 consecutive years. PARTICIPANTS: One hundred
      sixty-eight patients (186 eyes), younger than 18 years, with vitreous hemorrhage
      not secondary to active retinopathy of prematurity (ROP). METHODS: Charts were
      reviewed and data were compiled with special attention to demographic
      information, diagnosis, examination findings, visual acuity (VA) on presentation
      and last follow-up, treatment type, and length of follow-up. MAIN OUTCOME
      MEASURES: Etiologies, presenting symptoms, initial and final VAs, and management
      modalities. RESULTS: Among 168 patients (186 eyes), the most common presenting
      symptom was decreased VA in older patients and strabismus and nystagmus in
      younger patients. Seventy-three percent of cases occurred secondary to manifest
      and occult trauma, with blunt (29.6%) and penetrating (24.7%) trauma being most
      common. Twenty-seven percent of hemorrhages occurred spontaneously, with
      regressed ROP being most common. Of the cases, 90.5% were unilateral and 9.5%
      were bilateral. Shaken baby syndrome accounted for 50% of bilateral cases. The
      most common management modalities were observation (50.0%) and incisional surgery
      (45.7%), but frequency of management modality varied by etiology. Visual
      outcomes, which were limited by variable follow-up and nonstandardized
      acquisition, were poorest with penetrating trauma and best with regressed ROP.
      There was no statistical difference in severe vision loss between children older
      than 8 years and younger than 8. CONCLUSIONS: Pediatric vitreous hemorrhage may
      have multiple etiologies, but manifest and occult trauma are most common.
      Regressed ROP is a common cause of spontaneous vitreous hemorrhage. A substantial
      proportion of patients with vitreous hemorrhage had severe vision loss, but
      outcomes were highly dependent on underlying etiology.

PMID- 16650683
TI  - Ocular hypertension and secondary glaucoma in children with uveitis.
AB  - PURPOSE: To identify the risk factors for ocular hypertension and secondary
      glaucoma in children with uveitis. DESIGN: Retrospective observational case
      series of 147 patient records. PARTICIPANTS: Two hundred fifty-six eyes of 147
      children with uveitis diagnosed before the age of 16 years. METHODS: Data were
      obtained from the medical records of children with uveitis evaluated at our
      institute from 1990 through 2004. MAIN OUTCOME MEASURES: Localization and course
      of uveitis (acute or chronic), underlying systemic disease, onset of ocular
      hypertension, onset of secondary glaucoma, treatment with steroids, antinuclear
      antibodies (ANAs), lens extractions, number of blind eyes at onset and during
      follow-up, and the duration of follow-up. RESULTS: Elevated intraocular pressure
      developed in 35% of children with pediatric uveitis regardless of the form or
      type of uveitis during a follow-up of 5 years. Secondary glaucoma, however,
      developed more frequently in juvenile idiopathic arthritis-associated uveitis
      (38%) compared with other forms of uveitis (11%) and more frequently in children
      with uveitis who were ANA positive (42%) than in those who were ANA negative
      (6%). Elevated intraocular pressure occurred in two thirds of all children within
      the first 2 years after the diagnosis of uveitis. Except for patients with
      juvenile idiopathic arthritis-associated uveitis, periocular steroid injections
      represented an additional risk factor for secondary glaucoma, but this risk was
      limited to the early phase of the disease process. CONCLUSIONS: In children with
      uveitis in this series, juvenile idiopathic arthritis-associated uveitis and ANA
      positive uveitis without evidence of arthritis are the most important risk
      factors for developing secondary glaucoma.

PMID- 16650684
TI  - Incorrect IOL selection.

PMID- 16650685
TI  - Pseudomonas keratitis.

PMID- 16650686
TI  - Submacular surgery trials.

PMID- 16650688
TI  - Macular edema treatment.

PMID- 16650689
TI  - Retinal vessel diameter.

PMID- 16650691
TI  - Transformation of nevus to melanoma.

PMID- 16650692
TI  - Ganciclovir implant.

PMID- 16650693
TI  - 25-gauge vitrectomy.

PMID- 16650695
TI  - Triamcinolone for chalazia.

PMID- 16650696
TI  - Impact of being "on call".

PMID- 16650697
TI  - Medical student education.

PMID- 16650698
TI  - Cell-specific localization of progesterone receptors in the bovine ovary at
      different stages of the oestrous cycle.
AB  - This immunohistochemical study describes the localization of progesterone
      receptors (PR) in the bovine ovary of 23 cows at different stages of the oestrous
      cycle. In primordial, primary and secondary follicles the score for PR in the
      follicle cells increased progressively with the maturation of the follicle. In
      vital tertiary follicles and cystic atretic follicles a moderate score for PR was
      found, while in obliterative atretic follicles the score was much lower. Scores
      were high in corpora hemorrhagica, low in corpora lutea and still lower in
      corpora albicantia. Low PR scores were also found in the tunica albuginea and
      surface epithelium. Cyclic variations of PR immunoreactivity were manifest in
      most ovarian tissues. Follicular scores for PR were high in oestrus and decreased
      during the following stages, whereas scores in corpora lutea cells varied
      according to a characteristic pattern with high levels during oestrus and
      metoestrus. The variations in the scores for PR in the different ovarian cell
      types suggest a cell-specific and cycle-dependent influence of progesterone. A
      negative correlation was found between the PR scores and the plasma progesterone
      concentration.

PMID- 16650699
TI  - Reasons and risk: factors underlying women's perceptions of susceptibility to
      osteoporosis.
AB  - OBJECTIVES: To assess women's perceptions of risk for osteoporosis and to
      identify factors that shape those perceptions. METHODS: A community sample of 358
      women (aged 40-86) rated their perceived risk of osteoporosis and provided
      detailed information about factors underlying their risk perceptions. Their open
      ended responses were content analysed. RESULTS: On average, participants believed
      they were less likely to develop osteoporosis than other women their age. In all,
      63% perceived their risk as lower than other women their age; only 16% as higher.
      In explaining their risk, women mentioned more risk-decreasing factors than risk
      increasing factors. Women who rated their risk as low attributed their risk
      primarily to their own preventive behaviors (e.g. taking calcium, exercising),
      whereas women who rated their risk as high attributed their risk primarily to
      their family history. Risk-increasing and risk-decreasing personal actions,
      hereditary factors, and physiological factors accounted for 53% of the variance
      in perceived risk for osteoporosis. Only one-half and one-third of all women,
      however, mentioned calcium consumption and exercise, respectively, as protective
      factors employed to reduce osteoporosis risk. Women also held misconceptions
      about osteoporosis risk and protective factors. CONCLUSIONS: The current findings
      yield a detailed portrait of women's risk perceptions for osteoporosis.
      Increasing awareness of osteoporosis should be a priority for future osteoporosis
      prevention campaigns. Interventions should address misconceptions women may hold
      about their risk for the disease and promote specific behavioral strategies for
      osteoporosis prevention.

PMID- 16650700
TI  - Cyclodextrin-containing poly(ethyleneoxide) tablets for the delivery of poorly
      soluble drugs: potential as buccal delivery system.
AB  - The aim of this work was to develop a tablet for the buccal delivery of the
      poorly soluble drug carvedilol (CAR), based on poly(ethyleneoxide) (PEO) as
      bioadhesive sustained-release platform and hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) as modulator of drug release. As first, PEO tablets loaded with
      CAR/HPbetaCD binary systems with different dissolution properties were tested for
      CAR and HPbetaCD release features and compared to PEO tablets containing only
      CAR. When the drug was incorporated as CAR/HPbetaCD freeze-dried product, all CAR
      content was released from the tablet in about 10 h, displaying a constant release
      regimen after a transient. The effect of HPbetaCD incorporation on the release
      mechanism, was rationalized on the basis of the interplay of different physical
      phenomena: erosion and swelling of the tablet, drug dissolution, drug counter
      diffusion and complex formation. In the second part of the study, the potential
      of HPbetaCD-containing PEO tablets as buccal delivery system for CAR was tested.
      It was found that the incorporation of HPbetaCD in the tablet did not alter
      significantly its good adhesion properties. The feasibility of buccal
      administration of CAR was assessed by permeation experiments on pig excised
      mucosa. The amount of CAR permeated from PEO tablet was higher in the case of
      HPbetaCD-containing tablets, the maximum value being obtained for CAR/HPbetaCD
      freeze-dried system. Our results demonstrate that, when the tablet is employed as
      transmucosal system, the role of drug dissolution enhancement in the hydrated
      tablet is much more relevant than in solution for increasing the delivery rate.

PMID- 16650701
TI  - Use of a molecular form technique for the penetration of supersaturated solutions
      of salicylic acid across silicone membranes and human skin in vitro.
AB  - Permeation enhancement of salicylic acid (SA) from supersaturated solutions
      formed using a 'molecular form' technique was investigated. In a conventional
      cosolvent technique, two solvents are used, one in which the drug is considerably
      more soluble than the other. Propylene glycol and water have been predominantly
      used as cosolvents to create supersaturation in skin permeation enhancement. In
      this paper, we report the use of buffer solutions with different pHs as media for
      producing different molecular forms. Supersaturated solutions were prepared using
      pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model
      silicone membranes and human skin were used. Hydroxypropyl methyl cellulose
      (HPMC) was employed to stabilise the supersaturated states. Stability data showed
      that while the SA supersaturated solutions without HPMC crystallised between 15
      min and 46 h depending on the degree of supersaturation, the solutions with HPMC
      were stable for more than 2 months. The flux of SA increased with the degree of
      saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture.
      Although the fluxes of SA with and without HPMC were similar both through
      silicone membrane and human skin, HPMC was found to be effective in increasing
      the stability of supersaturated solutions of SA.

PMID- 16650702
TI  - Comparison of free and bound iodine and iodide species as a function of the
      dilution of three commercial povidone-iodine formulations and their microbicidal
      activity.
AB  - Equilibrium dialysis on povidone-iodine-solutions (Braunol, standardized Betadine
      and non-standardized iso-Betadine reveal that the amount of available iodine,
      free iodine, iodide and triiodide varies significantly both in the undiluted and
      diluted forms. These differences are reflected in the different bactericidal
      activity against Staphyloccus aureus as determined by the standard quantitative
      in vitro suspension test. The amount of available iodine is not an appropriate
      measure for an assessment of the microbicidal activity. For this, the free iodine
      has to be determined by means of equilibrium dialysis. The free iodine
      concentration in the Braunol concentrate was found to be 22 mg/L, in the
      standardized Betadine 9.7 mg/L and in the non-standardized Betadine concentrate
      only 2.1mg/L. Because of the atypical behaviour of iodophores and the increase of
      free iodine at dilution and because of a bactericidal level of free iodine of
      5mg/L, Braunol and standardized Betadine can be employed as disinfectant as such,
      iso-Betadine has to be diluted before use. Summarizing all results, it can be
      stated that Braunol is superior to standardized Betadine and unstandardized iso
      Betadine both as to the release of free iodine in the undiluted and in the
      diluted forms as in the killing rate of S. aureus.

PMID- 16650704
TI  - Identification and separation of DNA mixtures using peak area information.
AB  - We introduce a new methodology, based upon probabilistic expert systems, for
      analysing forensic identification problems involving DNA mixture traces using
      quantitative peak area information. Peak area is modelled with conditional
      Gaussian distributions. The expert system can be used for ascertaining whether
      individuals, whose profiles have been measured, have contributed to the mixture.
      It can also be used to predict DNA profiles of unknown contributors by separating
      the mixture into its individual components. The potential of our probabilistic
      methodology is illustrated on case data examples and compared with alternative
      approaches. The advantages are that identification and separation issues can be
      handled in a unified way within a single probabilistic model and the uncertainty
      associated with the analysis is quantified. Further work, required to bring the
      methodology to a point where it could be applied to the routine analysis of
      casework, is discussed.

PMID- 16650703
TI  - Deafness associated changes in expression of two-pore domain potassium channels
      in the rat cochlear nucleus.
AB  - Two-pore domain potassium channels (K(2PD)+) play an important role in setting
      resting membrane potential by regulating background leakage of potassium ions,
      which in turn controls neuronal excitability. To determine whether these channels
      contribute to activity-dependent plasticity following deafness, we used
      quantitative real-time PCR to examine the expression of 10 K(2PD)+ subunits in
      the rat cochlear nucleus at 3 days, 3 weeks and 3 months after bilateral cochlear
      ablation. There was a large sustained decrease in the expression of TASK-5, a
      subunit that is predominantly expressed in auditory brain stem neurons, and in
      the TASK-1 subunit which is highly expressed in several types of cochlear nucleus
      neurons. TWIK-1 and THIK-2 also showed significant decreases in expression that
      were maintained across all time points. TWIK-2, TREK-1 and TREK-2 showed no
      significant change in expression at 3 days but showed large decreases at 3 weeks
      and 3 months following deafness. TRAAK and TASK-3 subunits showed significant
      decreases at 3 days and 3 weeks following deafness, but these differences were no
      longer significant at 3 months. Dramatic changes in expression of K(2PD)+
      subunits suggest these channels may play a role in deafness-associated changes in
      the excitability of cochlear nucleus neurons.

PMID- 16650705
TI  - Autosomal STR data on the enigmatic Andaman Islanders.
AB  - We have analyzed nine autosomal STR loci (D3S1358, vWA, FGA, D8S1179, D21S11,
      D18S51, D5S818, D13S317, and D7S820) in 97 samples of enigmatic Andaman islanders
      including: 15 Great Andamanese, 46 Onge and 36 Nicobarese. Data was compared with
      the available data on Indian and South East Asian populations. Heterozygosity
      (H), power of discrimination (PD), probability exclusion (PE), typical paternity
      index (TPI), polymorphism information content (PIC), AMOVA and Arlequin analysis
      were carried out. Average heterozygosity observed was high and almost equal in
      all the populations. Similarly, PD, PE, TPI and PIC have been almost equal in all
      the populations.

PMID- 16650706
TI  - Population data of six STR loci using hexaplex PCR amplification and typing
      system, "Midi-6" in four regional populations in Japan.
AB  - The genetic differences of the allele frequency distributions for six STR loci
      (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290) among regions in
      Japan were examined using our recently designed hexaplex amplification and typing
      system, "Midi-6" newly named, to construct a database in the Japanese population.
      Genotypes at six loci were analyzed in 198, 200, 175, and 196 individuals from
      the area of Akita, Nagoya, Oita, and Okinawa, respectively, in Japan. The allele
      frequency distributions were significantly different (p<0.05) at from one to five
      loci among the four populations when compared pairwise. Significant differences
      were also observed at two or three loci between Oita- or Okinawa-Japanese and the
      "pooled" population (n=769), respectively. However, since F(ST) (theta) values
      were extremely low (<0.05), ranging from 0.0020 to 0.0118 for six loci, genetic
      differentiation within the pooled Japanese population was negligible. Therefore,
      it suggested that the data of the allele frequencies at six loci in the pooled
      population would be employed as the base of calculation for statistical
      probabilities.

PMID- 16650707
TI  - LC-MS/MS analysis of fentanyl and norfentanyl in a fatality due to application of
      multiple Durogesic transdermal therapeutic systems.
AB  - Fentanyl is a potent synthetic narcotic analgesic administered in the form of a
      transdermal patch for the management of chronic pain. A 78-year-old woman with a
      history of cancer was found dead in bed. She was lying on her back. The external
      examination revealed 10 Durogesic transdermal therapeutic systems (100 microg/h
      fentanyl) on the body. Liquid-liquid extraction and liquid chromatography tandem
      mass spectrometry with electrospray source in positive ionization mode was
      applied for the quantitation of fentanyl and its major metabolite norfentanyl in
      the post-mortem samples. Fentanyl-d5 and norfentanyl-d5 were used as internal
      standards. Multiple reaction monitoring was used for specific detection.
      Calibration was performed by addition of standard solutions to drug-free matrix
      (blood, urine and liver) prior to extraction. The method showed good linearity
      for fentanyl and norfentanyl over a concentration range of 5-150 microg/L in
      reconstituted extracts with coefficients of determination equal or greater than
      0.998. Percent mean within-day precision and accuracy of 0.9-1.0% and 99.4-101.1%
      for fentanyl and 2.0-4.5% and 93.1-101.0% for norfentanyl were obtained. Mean
      extraction recoveries varied between 95.5% and 100.3% for fentanyl and 39.2-57.4%
      for norfentanyl. The following fentanyl (norfentanyl) concentration in the post
      mortem samples were measured; 28.6 microg/L (3.0 microg/L) in right and 28.2
      microg/L (3.5 microg/L) in left subclavian blood, 21.3 microg/L (<2 microg/L) in
      right and 20.9 microg/L (<2 microg/L) in left femoral blood, 37.6 microg/L (4.2
      microg/L) in right and 33.9 microg/L (4.4 microg/L) in left ventricular blood,
      282.9 microg/L (121.2 microg/L) in urine, 688.2 microg/L in stomach contents,
      122.5 microg/L (25.4 microg/L) in bile, 19.5 microg/L (< 2 microg/L) in vitreous
      humour, 203.0 microg/kg (26.6 microg/kg) in liver and 78.6 microg/kg (46.3
      microg/kg) in kidney. We concluded that the woman's death was caused by acute
      intoxication with fentanyl. The manner of death was presumed to be suicide due to
      excessive administered Durogesic transdermal therapeutic systems.

PMID- 16650708
TI  - Gel permeation chromatography of dextrans in parenteral solutions: calibration
      procedure development and method validation.
AB  - We describe development and validation of a gel permeation chromatographic (GPC)
      method for dextrans in parenteral solutions. The GPC method was adopted from USP
      monographs on Dextran 40 and Dextran 70 raw materials. The method was optimized
      with a mobile phase flow rate of 1 mL/min and column temperature of 40 degrees C,
      to sharpen dextran and dextrose peaks. An easy-to-use, curve-fitting program
      capable of non-linear regression was developed in-house, using Microsoft Excel
      and its Solver add-in to successfully meet the GPC calibration requirements for
      dextrans and dextrose, i.e., the experimental molecular weights within 100+/-5%
      of the known molecular weights for dextrans and molecular weight of dextrose
      within 180+/-2 Da. The GPC method was validated in terms of its stability
      indicating nature, robustness (column temperature of 40+/-3 degrees C), accuracy
      (lack of effects of pH and concentration of dextrans or matrix components), and
      precision (repeatability and intermediate). Molecular weight distribution of
      dextrans were unchanged when the dextran containing test solutions were subjected
      to forced degradation using heat, light (daylight and UV light), extreme alkaline
      conditions or oxidative conditions. The method was capable of detecting changes
      in molecular weight distribution caused by degradation under extreme acidic
      conditions and heat, thereby confirming the stability indicating nature of the
      method. The concentration of Dextran 40 and Dextran 70 (75-125% of the nominal
      assay concentration), matrix components (108-111% of their nominal
      concentrations), and solution pH (pH 3-7 for Dextran 40 solutions and pH 4-7 for
      Dextran 70 solutions) did not affect the measured molecular weight distribution
      of Dextran 40 or Dextran 70. The method was precise with %R.S.D. of less than 1%
      for M (W) values of Dextran 40 or Dextran 70.

PMID- 16650709
TI  - Flow injection potentiometric determination of chlorpromazine.
AB  - New chlorpromazine selective electrodes with a tubular arrangement and no
      internal reference solution are proposed. Selective membranes are of poly(vinyl
      chloride) (PVC) with the tetraphenylborate.chlorpromazine (TPB.CPZ) ion-exchanger
      dissolved in o-nitrophenyl octyl ether (oNPOE). Analytical features of the
      electrodes were evaluated on a single-channel flow assembly having 500 microl
      injection volumes and flow-rates of 4.5 ml min(-1). For a carrier solution of 3.3
      x 10(-3)M in sodium sulphate, Nernstian response was observed over the
      concentration range 1.0 x 10(-5) to 1.0 x 10(-2)M. Average slopes were about 59
      mV decade(-1) and squared correlation coefficients were >0.9984. Slight hiper
      Nernstian behaviour was observed in buffer solutions of 4.4 pH; average slopes
      were of 62.06 mV decade(-1). The electrode displayed a good selectivity for CPZ,
      with respect to, several foreign inorganic and organic species. The selective
      electrodes were successfully applied to the analysis of pure solutions and
      pharmaceutical preparations. Proposed method allows the analysis of 84 samples h(
      1), producing wastewaters of low toxicity. The proposed method offers the
      advantage of simplicity, accuracy, applicability to coloured and turbid samples,
      and automation feasibility.

PMID- 16650710
TI  - Changes in ghrelin levels of plasma and proventriculus and ghrelin mRNA of
      proventriculus in fasted and refed layer chicks.
AB  - This is a test-report of ghrelin levels in plasma and proventriculus, the
      glandular portion of the avian stomach, by using a specific radioimmunoassay for
      acylated ghrelin, as well as the expression of the ghrelin gene in the
      proventriculus after a 12-h fasting period followed by a 6-h feeding period with
      6-day-old layer chicks. After fasting, the plasma ghrelin levels increased from
      21.3+/-4.5 to 32.9+/-5.0 fmol/ml, but once refed it returned to the control
      value. After fasting, the ghrelin mRNA and the peptide levels in the
      proventriculus increased, and ghrelin mRNA levels remained high but once refed
      the ghrelin content returned to the control level. Furthermore, in order to
      examine the effect of increased circulating ghrelin on food intake, a bolus
      intravenous injection of 500 pmol of chicken ghrelin was given to 8-day-old
      chicks. The ghrelin injection did not cause any significant changes in food
      intake. These results indicate that the levels of ghrelin and its mRNA with layer
      chicks are altered according to the feeding state and this in a similar manner as
      has been observed in mammals. Unlike in mammals, an increase in circulating
      ghrelin does not cause the promotion of food intake in chicks.

PMID- 16650712
TI  - Obsessive-compulsive spectrum disorders: a multidimensional approach.
AB  - One advantage of conceptualizing two disorders as related lies in the possibility
      that a similar treatment is effective for both conditions. The approach taken in
      this paper is somewhat different, however. The authors have argued that although
      a particular psychobiologic process may be relevant to OCD and obsessive
      compulsive conditions, it may be disrupted indifferent ways in various conditions
      that fall along a spectrum. If so, differ-ent obsessive-compulsive spectrum
      disorders may well require different treatments. Thus, although OCD and
      trichotillomania can be conceptualized in terms of the pathologic release of
      motor programs, they may require rather different treatment approaches.
      Furthermore, in the absence of a detailed understanding of the psycho-biology of
      OCD and related disorders, conceptualizations of obsessive-compulsive spectrum
      disorders can remain only preliminary in nature. The involvement of cortico
      striatal circuitry in OCD suggests that obsessive-compulsive spectrum disorders
      may be characterized by involvement of these paths. Striatal circuits mediate
      many different functions (including reward processes), however, and are involved
      in many disorders. Similarly, the involvement of serotonergic neurotransmitters
      in OCD suggests that these neurotransmitters are central to defining spectrum
      disorders.Again, however, serotonin plays a role in many functions (including
      impulse control) and mediates many different disorders. Much work remains to be
      done to delineate optimally the obsessive-compulsive spectrum of disorders.
      Nevertheless, significant progress has been made. Empiric data demonstrate
      involvement of cortico-striatal circuitry in a number of putative obsessive
      compulsive spectrum disorders [43]. Similarly, data demonstrate that a selective
      response to serotonin-reuptake inhibitors is seen in a range of these different
      spectrum disorders. As further progress is made in understanding the cognitive
      affective neuroscience of OCD and related conditions, constructs about obsessive
      compulsive spectrum disorders will become increasingly sharp.

PMID- 16650713
TI  - Obsessive-compulsive and spectrum disorders in children and adolescents.
AB  - The available literature indicates that OCD affecting children and adolescents is
      highly prevalent. Pediatric-onset OCD seems to share important similarities with
      the adult disorder but also shows important differences. For example, the
      clinical phenotype of OCD is remarkably consistent at all ages with some
      allowances for developmental expression. Pediatric patients frequently
      demonstrate poor insight into the nature of their obsessions, which in
      association with their limited verbal expression may make the diagnosis more
      difficult. Obsessions involving fear of harm and separation, compulsions without
      obsessions, and rituals involving family members are more common in younger
      patients. Treatment response,including serotonergic specificity and the need for
      robust dosing, is another feature shared by early- and adult-onset OCD. Imporfant
      differences across the life span can also be identified. Perhaps the clearest
      difference pertains to age of onset. Age-at-onset data have shown a bimodal
      distribution of age of onset of OCD, with one peak in preadolescent childhood and
      another peak in adulthood. Another distinction between child and adult OCD is
      gender representation. Whereas adult studies report equal gender representation
      or a slight female preponderance, pediatric clinical samples are clearly male
      predominant. Patterns of psychiatric comorbidity in pediatric OCD show high rates
      of tic and mood and anxiety disorders, similar to the patterns in adults, but
      also show a distinct association with disruptive behavior disorders (ADHD and
      oppositional defiant disorder) and other specific and pervasive developmental
      disorders. Family studies indicate that the disorder is highly familial and that
      a childhood onset of the disorder seems to be associated with a markedly
      increased risk for familial transmission of OCD, tic disorders, and ADHD. Both
      scientifically and clinically, the recognition of developmentally specific OCD
      phenotypes may be valuable. For example, research efforts aimed at identifying
      OCD-associated genes are likely to be more successful if developmentally
      homogeneous samples are studied instead of combining data from children,
      adolescents, and adults, as has been common in OCD studies. Clinical management
      is also informed by an appreciation of the unique cor-relates of OCD affecting
      youth, especially comorbidity with chronic tic dis-orders and ADHD and their
      impact on treatment. The so-called "spectrum disorders" related to OCD are less
      prominent in children and adolescents than in adults. Although sharing some
      features with typical OCD, these symptoms are less clearly ego-dystonic and less
      anxiety producing, frequently provide a measure of gratification, and are less
      responsive in general to SSRIs. Often cognitive antecedents to these behaviors
      are less well developed than in more typical OCD, and behavioral interventions
      are the mainstay of treatment but with more variable success.

PMID- 16650714
TI  - Animal models of obsessive-compulsive disorder: rationale to understanding
      psychobiology and pharmacology.
AB  - Animal models have shown progressive development and have undoubtedly proven
      their supportive value in OCD research. Thus, various animal models have
      confirmed the importance of the 5-HT [72-74] and dopamine systems [104,111] in
      the neurobiology and treatment of OCD. Given the neurochemical, emotional, and
      cognitive complexity of the disorder, how-ever, animal models are being used to
      investigate more and more complicated neurochemical and behavioral theories
      purported to underlie OCD. The lever-press model, for example, has implicated
      deficient response feed-back in a neural system that regulates operant behavior
      [74]. Studies on stereotypic movement disorder [89] have opened a new avenue of
      investigation into the neurobiology of stereotypy that may be applicable to more
      complex syndromes such as OCD. Models that have focused on specific
      neuropsychologic aspects of OCD such as reward [74], displacement
      behavior[63,101], perseveration and indecisiveness [73,102], and spontaneous
      stereotypy [90,94] are important in their attempt to unify the diverse behavioral
      manifestations of this disorder. It is clear that for a deeper, more holistic
      understanding of OCD, multiple animal models will be needed to allow
      investigation of the various aspects of the disorder and to provide convergent
      validation of the research findings. The heterogeneous nature of OCD, the various
      subtypes that exist within the disorder, and the range of obsessive-compulsive
      spectrum disorders suggest that particular questions regarding OCD may be
      addressed best by us-ing a particular ethologic model, whereas other questions
      might require a pharmacologic model or a combination of both for meaningful
      results[62,115]. Genetic models will be extremely useful for studying the
      genetics of pathologic behavior and for relating these findings to neuroanatomic
      and neurochemical changes in the model (eg, DICT-7 mice as a model for Tourette's
      syndrome and OCD). Neither ethologic nor pharmacologic models, however, can
      assess whether the "compulsive" behavior is a response to an "obsessive" anxiety
      or fear. Perhaps the symptoms seen in patients who have OCD, which may be
      exacerbated by everyday stress, are analogous to displacement behaviors in
      animals and also reflect some form of anxiety or stress [98]. In this regard, the
      bank vole model [116]has provided evidence that previously developed stereotypies
      increase markedly after acute stress and argues that healthy individuals
      "habituate" to everyday stress, whereas patients who have OCD do not.
      Interindividual variation in behavioral response and attempts to replicate
      studies in different laboratories often is the nemesis of the behavioral
      scientist. Small within- and between-subject variability is usually desirable,
      how-ever, because there are cases in which the study of the variability of the
      model could lead to a better understanding of the disorder. Variability can-not
      always be considered an error; it is possible that previously disregarded
      neuronal systems may have a place in the observed variation and, indeed, in the
      pathophysiology of OCD. In this regard, SRIs are not always effective for OCD
      [6,29,30] such that a lack of effect in a model may reflect an un-known
      neurobiological basis for compulsive behavior in a sub-group of SRI refractory
      patients. Similarly, separating the afflicted (ie, working with animals that show
      greater behavioral change in a model and/or after drug treatment) would have
      distinct benefits. To increase successful implementation of an ethologic animal
      model, especially when reinforcement models or signal attenuation models are
      used,the laboratory must be equipped with the essential behavioral testing
      apparatus as well as the operant chambers/rooms in which to conduct the train-ing
      and data collection. Quantification of certain stereotypy behaviors also requires
      experienced or trained observers. An illustration of the difficulty in measuring
      behavioral changes is that in the rewarded alternation model,a good response to
      behavioral treatment (alternation training) may lead to a floor effect [73]
      which, after successful drug treatment of the animal,produces no residual
      persistence (ie, measurable behavioral change) on which a drug treatment can be
      tested. Clearly, the choice of ethologic, pharmacologic, or genetic models should
      be considered carefully. A well-validated model may quell many of the limitations
      and considerations described previously. Noninvasive neuroimaging(eg, the use of
      small-animal single-photon emission CT) to explore the neuroanatomic basis of OCD
      offers an exciting future challenge, especially if combined with pharmacologic or
      ethologic models, and could confirm or ex-tend knowledge of the neuroanatomy of
      OCD. Although studies to investigate further the interactive role of 5-HT,
      dopamine, GABA, and glutamate are still needed, the role of neuroactive peptides
      such as cholecystokinin, corticotrophin-releasing factor, neuropeptide Y,
      tachykinins (ie, substance P),and natriuretic peptides in OCD should also be
      considered. Genetically engineered animal models will become increasingly
      valuable in combination with new technologies such as gene-chip microarrays, RNA
      interference, and advanced proteomics that will help further the understanding of
      OCD. Animal models of OCD are poised to play a vital role in extending the
      knowledge of the disorder now and in the future.

PMID- 16650715
TI  - Common and distinct neural correlates of obsessive-compulsive and related
      disorders.
AB  - Obsessive-compulsive disorder (OCD) often co-occurs with other anxiety disorders
      and a number of other disorders of similar phenomenology known as the "OCD
      spectrum" disorders. Neurobiologically, it is unclear how all these disorders
      relate to each other. The picture is further complicated by the clinical
      heterogeneity of OCD itself. This article reviews the literature on the common
      and distinct neural correlates of OCD, its symptom dimensions, and other anxiety
      and OCD spectrum disorders with the hope of providing a conceptual and heuristic
      framework to help understand the relationship between these phenomena.

PMID- 16650716
TI  - The current status of association studies in obsessive-compulsive disorder.
AB  - During the last 2 decades, a large number of association studies have been
      dedicated to disentangling the genetic components that may be involved in the
      etiology of OCD. The preliminary and frequently in consistent nature of the data
      represented in the majority of OCD psychiatric genetic-association studies may
      seem discouraging. Failure to replicate, and thus to confirm, previously
      identified susceptibility loci could result from a number of reasons, including
      the potential for population admixture, the clinical heterogeneity of OCD, small
      sample sizes (and subsequent lack of power),publication bias, epistasis, or
      failure to account for multiple testing. Various methods of accounting for these
      confounders do exist and should be implemented in any genetic-association study
      that is to be regarded as robust and replicable. Discrepancy between results,
      however, might be ascribed to the underlying genetic differences between the
      populations in the respective studies (ie, the investigated variant may be in
      linkage disequilibrium with the causal variant in one population but not in
      another). Such discrepancies are difficult to reconcile in single-locus
      association studies; haplotype analyses(in which a number of variants, usually
      single-nucleotide polymorphisms occurring on the same gene, are analyzed as a
      unit) may be able to resolve these uncertainties. Investigating epistatic
      interactions between variants in other genes that might be involved in the same
      physiologic pathways would be an alternative means of deciphering the reason for
      discrepant genetic association results.A valid means of increasing the power (by
      reducing background noise)would be to stratify the patient sample according to
      clinically defined sub-types, such as obsession and compulsion subtypes, age at
      onset of the disorder, and severity of the disorder. Although many of the OCD
      genetics studies have incorporated investigations of these subtypes
      [65,66,68,77,84-86,89,107,118,132,133,145,148,149], the number of subjects
      decreases after stratification, thereby limiting the power of the studies. It may
      therefore be useful to employ other quantitative approaches in the design of the
      investigation: the possibility should be considered that OCD symptoms can be
      broken down into multiple dimensions that are continuous with the normal
      population [150]. This division would represent an important route to
      disentangling the complex inheritance of OCD. The results obtained from genetic
      investigations should be incorporated with clinical and epidemiologic parameters
      to elucidate correctly the cause of OCD. Future studies should also be extended
      to incorporate the screening of more polymorphisms, because high-resolution
      mapping within specific chromosomes will improve knowledge regarding the impact
      of genetic diversity within the genes or linked chromosomal regions in OCD. The
      advantages ofa gene-based over a single-nucleotide polymorphism based approach
      are becoming ever more apparent [151]. Therefore, a more complete assessment of
      candidate genes, possibly using haplotype blocks that span larger regions,is
      proposed. In addition, increasing the amount of information on human genome
      sequences and polymorphisms will make it possible to characterize the amount of
      sequence variation expressed in the brain and to delineate the potential effects
      that these variations may have on the development of OCD. Knowledge of new
      functional variants will emerge as researchers gain an understanding of the
      potential for genetic variants in the coding and regulatory regions to impact
      gene expression.

PMID- 16650717
TI  - Immunology of obsessive-compulsive disorder.
AB  - Childhood OCD often develops into a chronic illness that lasts decades. Proof
      that some type of immunotherapy (such as antibiotic prophylaxis) could
      significantly reduce recurrence or exacerbation of symptoms of OC or tics would
      suggest a supportive role for immune triggers in the onset or worsening of these
      conditions and provide additional tools for improving outcome. The validity of
      PANDAS will continue to be questioned, however,because demonstrating a clear
      causation will be difficult on a background ofa common childhood illness. Along
      with the previously mentioned immuno-therapy study, validation of the PANDAS
      phenotype (broadly interpreted)would be advanced from new and continued research
      in the following areas: (1) prospective studies to identify infectious triggers
      in the onset and exacerbations of OCD spectrum disorders, (2) biological measures
      for immune and genetic susceptibility, and (3) large scale epidemiological
      studies demonstrating the relationship between infection and OCD spectrum
      disorders. The assimilation of these study results should allow for elucidation
      of the immune system's role in the onset and maintenance of OCD.

PMID- 16650718
TI  - Tourette's Syndrome.
AB  - This article has focused on TS, and the relationship between TS and OCD has been
      addressed from different perspectives. In patients who have OCD, the presence of
      TS seems to have some impact in the clinical manifestation of OCD symptoms. One
      of the main features of tic-related OCD is the frequent presence of sensory
      phenomena preceding the compulsions, in the absence of obsessions. Genetic
      epidemiologic studies provide consistent evidence for the association between TS
      and OCD. Although no major loci have been identified so far, family and
      segregation analysis studies support the assumption that genes play a major role
      in the etiology of TS and related disorders. Genes interact with environmental
      factors,which can modulate the expression of TS or OCD and determine the onset of
      these disorders. Neuroimaging studies suggest that the pathophysiology of TS
      encompasses projections of primary, secondary, and somato sensory cortex to the
      putamen, dorsolateral caudate nucleus, and globus pallidus,whereas the
      pathophysiology of OCD involves more ventral structures,such as orbitofrontal
      caudate-thalamic-cortical areas. Current treatment strategies for TS include
      education, behavioral therapy, pharmacotherapy,and support from patients
      associations. Alfa-adrenergic agents such as guanfacine and clonidine are first
      choice treatments for TS; typical antipsychotics are more effective but are
      troublesome because of their long-term side-effect profiles. For comorbid TS plus
      OCD, each condition should be treated with its respective first-line option.
      Nonetheless, for patients who have tic-related OCD who are unresponsive to
      monotherapy with serotonin reuptake inhibitors, augmentation of serotonin
      reuptake inhibitors with atypical antipsychotics may be of benefit. Despite
      important advances, re-search is needed to clarify further the biologic and
      behavioral aspects of TS and its relationship with the frequently associated
      conditions, with particular attention to their management and prognosis.

PMID- 16650719
TI  - Understanding and treating trichotillomania: what we know and what we don't know.
AB  - This article reviews current issues in the understanding and clinical management
      of trichotillomania (TTM). After diagnostic considerations and epidemiology are
      discussed, a brief update on biologic and environmental precipitants is provided,
      and emerging research on possible TTM subtypes is discussed. Current strategies
      for assessing TTM and t heir applicability to clinical practice are reviewed, as
      is the current state of pharmacologic and nonpharmacologic treatments for the
      disorder. The article concludes with suggestions for future research and
      descriptions of the authors'research agenda.

PMID- 16650720
TI  - Hypochondriasis: conceptualization, treatment, and relationship to obsessive
      compulsive disorder.
AB  - Once considered exclusively as a problem secondary to other mental dis-orders
      (ie, mood disorders), HC is now known to occur quite often as a pri-mary
      diagnosis. A frequent drain on medical resources, patients who have HC can be
      viewed as suffering essentially from an anxiety disorder in which intense fear is
      focused on the possibility that they might be seriously physically ill or that
      such illness is imminent. The processes that contribute to the development and
      maintenance of such health anxiety consist largely of beliefs, assumptions, and
      behavioral responses that, although internally consistent with the perception of
      health-related threat, are erroneous and highly maladaptive in that they prevent
      the correction of erroneous perceptions of threat. There is growing evidence that
      this conceptualization leads to effective reduction in HC symptoms through
      cognitive-behavioral and pharmacologic treatments. By far the main obstacle to
      successful treatment of HC is the patient's reluctance to view the problem as
      anything other than physical. The authors have found, however, that patients
      appreciate their care providers showing a genuine understanding of their concerns
      and taking the time to offer a logical, coherent explanation and rationale for
      the need for psychological and psychiatric services.

PMID- 16650721
TI  - Body dysmorphic disorder.
AB  - BDD remains an understudied psychiatric disorder. Further research is required to
      establish its etiopathology and neurocognitive underpinnings. Its relationship to
      other psychiatric disorders requires clarification. Also needed is a much better
      understanding of the best treatments to adopt should conventional approaches (eg,
      SRIs, CBT) fail.

PMID- 16650722
TI  - Compulsive aspects of impulse-control disorders.
AB  - Impulsivity and compulsivity have been considered opposite poles of a continuous
      spectrum, but their relationship seems to be more complex. Disorders
      characterized by impulsivity often have features of compulsivity and vice-versa.
      Impulse-control disorders (ICDs) are characterized by repetitive behaviors and
      impaired inhibition of these behaviors, suggesting a similarity to the frequently
      excessive, unnecessary, and unwanted rituals of obsessive-compulsive disorder
      (OCD). There are, however, important differences be-tween ICDs and OCD. The
      construct of compulsivity as related to ICDs and OCD warrants additional
      investigation to identify the similarities and differences and to examine the
      implications for prevention and treatment strategies.

PMID- 16650723
TI  - Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive
      spectrum disorders.
AB  - This article reviews new developments of pharmacotherapy in obsessive-compulsive
      disorder (OCD) and OC spectrum disorders of the past five years. New developments
      primarily involved the ex-tension of evidence of efficacy of serotonin reuptake
      inhibitors(SRIs), the use of atypical antipsychotics in addition to SRIs for
      treatment refractory patients, the combination of pharmacotherapy with behavior
      therapy, and studies assessing predictors of response. Today, frontline
      pharmacological treatment of OCD still consists of drugs with potent serotonin
      reuptake inhibition proper-ties. In case of non-response, treatment options
      comprise adding another drug, increasing the dose, switching drugs, or changing
      the mode of delivery.

PMID- 16650724
TI  - Psychotherapy of obsessive-compulsive disorder and spectrum: established facts
      and advances, 1995-2005.
AB  - Dropout rates and refractory cases persist, for reasons that remain unexplained.
      There are few predictor variables and few innovative approaches to deal with
      them. New treatment approaches must be developed to improve treatment response
      even for the responders. Studies show that symptoms are reduced minimally (30%
      50%). No new ways of dealing with treatment-refractory cases have been developed.
      Studies now include more co-morbid cases, however, and their inclusion may
      account for some of the lack of progress in improvement rates. It needs to be
      seen whether patients who have one or more comorbid conditions do as well as
      patients who do not have comorbidity and whether the number or type of comorbid
      disorders accounts for treatment response. Perhaps better results would be seen
      with pure OCD cases. Certainly results now are more generalizable to clinical
      practice. Now it is important to look for alternative treatment approaches and to
      apply cognitive therapy to more specific problems. Cognitive therapy seems to be
      helpful with the disorders of the obsessive-compulsive spectrum. The attrition
      rate is lower when cognitive therapy is used in the treatment of hypochondriasis,
      and cognitive therapy also is helpful in reducing OVI , which is more severe in
      body dysmorphic disorder and hypochondriasis. The role of cognitive therapy in
      OVI needs further exploration.

PMID- 16650725
TI  - The validity of the letter memory test as a measure of memory malingering:
      robustness to coaching.
AB  - The letter memory test (LMT) is a computerized forced-choice test of malingering
      detection including two face valid difficulty manipulations: increase in target
      stimulus length and increase of response foils. Prior research suggests the LMT
      shows promise as a malingering detection measure. In the present study, the
      utility of the LMT in the identification of malingering was further explored,
      using a counterbalanced design in a simulated malingering sample. Prior work was
      extended by assessing the robustness of the LMT to coaching and assessing the
      effectiveness of an additional scoring method, utilizing the face valid
      difficulty manipulations. Results were consistent with prior research on the LMT,
      with the standard cutoff score yielding high indices of accuracy. The LMT showed
      no order effects and was superior to the 15-item test in accuracy indices. Both
      the standard LMT score and the proposed score based on difficulty manipulations
      were relatively robust to coaching. Overall, findings indicate the LMT is a
      viable contender among measures of memory malingering.

PMID- 16650726
TI  - Gastrointestinal-focused panic attacks among Cambodian refugees: associated
      psychopathology, flashbacks, and catastrophic cognitions.
AB  - Among Cambodian refugees attending a psychiatric clinic, we assessed
      psychopathology associated with gastrointestinal panic (GIP), and investigated
      possible causal mechanisms, including "fear of fear" and GIP-associated
      flashbacks and catastrophic cognitions. GIP (n=46) patients had greater
      psychopathology (Clinician-Administered PTSD Scale [CAPS] and Symptom Checklist
      90-R [SCL]) and "fear of fear" (Anxiety Sensitivity Index [ASI]) than did non-GIP
      patients (n=84). Logistic regression revealed that general psychopathology (SCL;
      odds ratio=4.1) and fear of anxiety-related sensations (ASI; odds ratio=2.4)
      predicted the presence of GIP. Among GIP patients, a hierarchical regression
      revealed that GIP-associated trauma recall and catastrophic cognitions explained
      variance in GIP severity beyond a measure of general psychopathology (SCL). A
      mediational analysis indicated that SCL's effect on GIP severity was mediated by
      GIP-associated flashbacks and catastrophic cognitions.

PMID- 16650727
TI  - Perception of memory ability and confidence in recollections in obsessive
      compulsive checking.
AB  - Inconsistencies in research on deficits in memory for actions in studies of
      obsessive-compulsive (OC) checking have refocused investigators on beliefs such
      as confidence in the accuracy of recall as a possible motivation for checking.
      Poor confidence in relation to recall may be specific (perceived poor recall for
      a particular event) or general (perceived poor memory ability for that class of
      events). The present study examines both perception of memory ability and
      confidence in recollections in OC checkers across a range of situations,
      obsessive and non-obsessive. These ratings were compared with those of non
      checking obsessional patients, anxious controls and non-clinical controls. OC
      checkers reported poorer perception of memory ability than other groups in
      situations for which they are responsible, both OC relevant and OC non-relevant.
      OC checkers also reported lower confidence in recollections compared to the other
      groups; this was specific to obsessional situations for which they are
      responsible. These findings are considered in the context of the cognitive model
      of OCD.

PMID- 16650729
TI  - The resuscitation greats. Bernard Lown and defibrillation.

PMID- 16650730
TI  - European Resuscitation Council guidelines for resuscitation 2005.

PMID- 16650731
TI  - Right ventricular infarction simulating the Brugada syndrome.

PMID- 16650732
TI  - Flow cytometry evaluation of lead and cadmium effects on mouse spermatogenesis.
AB  - Flow cytometry (FCM) is a powerful tool to evaluate cell DNA content and ploidy
      levels. We have assessed the accuracy of two protocols of nuclei isolation from
      paraffinized samples (P1 and P2) by comparing FCM results with those obtained
      using fresh material (F1-F3). After isolation, nuclei were stained with propidium
      iodide and quantitatively analysed by FCM for changes in germ cell ratios.
      Results obtained with Protocol P2 were similar to those obtained using the
      protocol that gave best results for fresh tissues (F2). Protocol P2 was then
      applied to paraffin embedded testicular samples from ICR-CD1 mice exposed to 1, 2
      and 3 mg CdCl(2)/kg bw by single subcutaneous injection, and to 74 and 100 mg
      PbCl(2)/kg bw administered in four repeated doses. The highest doses of CdCl(2)
      decreased the number of haploid (1C) cells and increased the number of diploid
      (2C), S phase and tetraploid (4C) cells. Treatment with PbCl(2) did not induce
      significant changes in testicular cells subpopulations. These results support the
      usefulness of FCM in evaluating the effect of toxic substances on mouse
      spermatogenesis, using both fresh and paraffinized material.

PMID- 16650733
TI  - Seroepidemiological study of toxoplasmosis in intellectual disability children in
      rehabilitation centers of northern Iran.
AB  - Serological studies revealed that toxoplasmosis has world wide distribution.
      Although the infection by Toxoplasma gondii is widely prevalent in humans and
      animals, the disease is uncommon and most of the acquired infections are
      asymptomatic. The important aspect of this parasitic infection is the probable
      danger of congenital transmission and its severe effects on the fetus. There have
      been many reports about the prevalence of anti-T. gondii antibody among different
      groups of people in Iran; however the epidemiological data in intellectual
      disability (ID) persons are rare. This study was performed to evaluate the
      seroprevalence of toxoplasmosis among the inhabitants of rehabilitation centers
      of northern Iran. A total of 336 serum samples (161 males, 175 females) were
      examined for the IgG antibodies by indirect immunofluorescense technique. First
      of all, 1:50 titer dilution was tested, in the cases of positive result, further
      dilutions (1:100, 1:200, 1:400, 1:800, 1:1600, and 1:3200) were prepared and the
      last dilution was recorded. Among 336 sera, 77.4% showed seropositivity by IFAT.
      The positive rates of males and females were 77.6% (125/161) and 80% (140/175),
      respectively. However, there were no significant differences between sexes.
      Comparing the age groups, the highest seropositive rate showed in 19 or higher,
      and their rates had a tendency to increase with age. Prevalence of the infection
      in 10 rehabilitation centers was not significant either. Nevertheless, our data
      (77.4%) in rehabilitation centers in northern Iran suggest that infection is the
      same as in many other reports in normal population in this area, therefore
      toxoplasmosis is not a major problem in rehabilitation centers of this
      geographical area.

PMID- 16650734
TI  - Phytophthora captiosa sp. nov. and P. fallax sp. nov. causing crown dieback of
      Eucalyptus in New Zealand.
AB  - A locally severe crown disease of exotic plantation Eucalyptus trees has been
      recorded periodically in New Zealand since 1986. Symptoms include leaf spots,
      petiole infection and twig and small branch lesions. Outbreaks of disease are
      episodic and individual trees may show marked variation in crown symptoms ranging
      from unaffected to total defoliation. Two previously unknown species of
      Phytophthora are associated with the disease. These are described and formally
      designated here as P. captiosa, from Eucalyptus botryoides and E. saligna; and P.
      fallax, from E. delegatensis, E. fastigata, E. nitens and E. regnans. Both P.
      captiosa and P. fallax have non-papillate, non-caducous sporangia and both are
      self-fertile. Phylogenetic analysis on the basis of ITS rDNA sequence data
      indicates they are closely related to each other but evolutionarily distant from
      the majority of described Phytophthora taxa. They share a common ancestor with
      another assemblage of Phytophthora lineages that includes P. insolita, P.
      macrochlamydospora and P. richardiae. Sporulation of P. captiosa and P. fallax
      has not been observed in the field. The mode of infection and spread of these non
      caducous Phytophthora species in the eucalypt tree canopy remains unknown. This
      issue, and the possible geographic origins of these two Phytophthora species are
      discussed.

PMID- 16650735
TI  - Comorbid diagnoses in patients meeting criteria for the schizophrenia prodrome.
AB  - While schizophrenia is often associated with a variety of concurrent psychiatric
      symptoms, little attention has been paid to the prevalence of psychiatric
      comorbidity in prodromal patients. The current study examines the presence of
      comorbid current and lifetime psychiatric conditions in prospectively identified
      prodromal patients. The results suggest that like their schizophrenic
      counterparts, prodromal patients experience a wide array of comorbid psychiatric
      syndromes, with the most common being Major Depressive Disorder and Cannabis
      Dependence. Results also suggest that Cannabis Dependence may be more common
      among prodromal versus help-seeking control patients. These findings lay the
      groundwork for further examination of the role that comorbid conditions play in
      the development, course, and severity of schizophrenia.

PMID- 16650736
TI  - Hearing impairment and psychosis: a replication in a cohort of young adults.
AB  - Previous work has demonstrated an association between hearing impairment and
      psychosis. In the current study, this association was studied in a cohort of
      young people. In addition, it was studied to what degree duration of hearing
      problems (i.e. onset earlier in life) impacted on risk. Data were derived from
      the Greek National Perinatal Survey, a prospective birth cohort study of 11,048
      neonates at baseline, 6594 seven-year olds at T1 and 3500 nineteen-year olds at
      T2. A significant association was found at age 19 years between the presence of
      hearing impairment and the presence of self-reported positive psychotic-like
      experiences (beta = 0.18, S.E. = 0.02, p < 0.000). In addition, this association
      was conditional on the duration of hearing problems, in that the association at
      age 19 years was stronger if hearing impairment had already been reported at age
      7 years (test for interaction: p = 0.022). These results replicate previous
      findings of an association between hearing impairment and psychosis, extend it to
      the age range of late adolescence, and suggest that longer duration is associated
      with stronger risk.

PMID- 16650737
TI  - Effects of albumin and erythrocyte membranes on spread monolayers of lung
      surfactant lipids.
AB  - Dipalmitoyl phosphatidylcholine (DPPC), one of the main constituents of lung
      surfactant is mainly responsible for reduction of surface tension to near 0 mN/m
      during expiration, resisting alveolar collapse. Other unsaturated phospholipids
      like palmitoyloleoyl phosphatidylglycerol (PG), palmitoyloleoyl
      phosphatidylcholine (POPC) and neutral lipids help in adsorption of lung
      surfactant to the air-aqueous interface. Lung surfactant lipids may interact with
      plasma proteins and hematological agents flooding the alveoli in diseased states.
      In this study, we evaluated the effects of albumin and erythrocyte membranes on
      spread films of DPPC alone and mixtures of DPPC with each of PG, POPC,
      palmitoyloleoyl phosphatidylethanolamine (PE), cholesterol (CHOL) and palmitic
      acid (PA) in 9:1 molar ratios. Surface tension-area isotherms were recorded using
      a Langmuir-Blodgett (LB) trough at 37 degrees C with 0.9% saline as the sub
      phase. In the presence of erythrocyte membranes, DPPC and DPPC+PA monolayers
      reached minimum surface tensions of 7.3+/-0.9 and 9.6+/-1.4 mN/m, respectively.
      Other lipid combinations reached significantly higher minimum surface tensions
      >18 mN/m in presence of membranes (Newman Keul's test, p<0.05). The relative
      susceptibility to membrane inhibition was [(DPPC+PG, 7:3)=(DPPC+PG,
      9:1)=(DPPC+POPC)=(DPPC+PE)=(DPPC+CHOL)]>[(DPPC+PA)=(DPPC)]. The differential
      response was more pronounced in case of albumin with DPPC and DPPC+PA monolayers
      reaching minimum surface tensions less than 2.4 mN/m in presence of albumin,
      whereas DPPC+PG and DPPC+POPC reached minimum surface tensions of around 20 mN/m
      in presence of albumin. Descending order of susceptibility of the spread
      monolayers of lipid mixtures to albumin destabilization was as follows:
      [(DPPC+PG, 7:3)=(DPPC+PG,
      9:1)=(DPPC+POPC)]>[(DPPC+PE)=(DPPC+CHOL)]>[(DPPC+PA)=(DPPC)] The increase in
      minimum surface tension in presence of albumin and erythrocyte membranes was
      accompanied by sudden increases in compressibility at surface tensions of 15-30
      mN/m. This suggests a monolayer destabilization and could be indicative of phase
      transitions in the mixed lipid films due to the presence of the hydrophobic
      constituents of erythrocyte membranes.

PMID- 16650738
TI  - Bioavailability of seocalcitol II: development and characterisation of self
      microemulsifying drug delivery systems (SMEDDS) for oral administration
      containing medium and long chain triglycerides.
AB  - By constructing ternary phase diagrams it was possible to identify two self
      microemulsifying drug delivery systems (SMEDDS) containing either medium chain
      triglycerides (MC-SMEDDS) or long chain triglycerides (LC-SMEDDS), with the same
      ratio between lipid, surfactant and co-surfactant. The SMEDDS ended up having a
      composition of 25% lipid, 48% surfactant and 27% co-surfactant, MC-SMEDDS:
      viscoleo, cremophor RH40, akoline MCM and LC-SMEDDS: sesame oil, cremophor RH40,
      peceol. Upon dilution with water both SMEDDS resulted in clear to bluish
      transparent microemulsions with a narrow droplet size of 30nm. The industrial
      usefulness of the developed SMEDDS was evaluated with regard to bioavailability
      and chemical stability using the vitamin D analogue, seocalcitol, as model
      compound. The absorption and bioavailability of seocalcitol in rats were
      approximately 45% and 18%, respectively, from both the MC-SMEDDS and LC-SMEDDS
      indicating similar in vivo behavior of the two formulations, despite the
      difference in nature of lipid component. There was no improvement in
      bioavailability by the use of SMEDDS, compared to the bioavailability achieved
      from simple MCT and LCT solutions (22-24%) (Grove, M., Pedersen, G.P., Nielsen,
      J.L., Mullertz, A., 2005. Bioavailability of seocalcitol. I. Relating solubility
      in biorelevant media with oral bioavailability in rats-effect of medium and long
      chain triglycerides. J. Pharm. Sci. 94, 1830-1838.). After 3 months' storage at
      accelerated conditions (40 degrees C/75% RH), a decrease in concentration of
      seocalcitol of 10-11% was found in MC-SMEDDS and LC-SMEDDS compared with a
      degradation of less than 3% for the simple lipid solutions of MCT and LCT. In
      this study the simple lipid solutions seem to be a better choice compared with
      the developed SMEDDS due to a slightly higher bioavailability and a better
      chemical stability of seocalcitol.

PMID- 16650739
TI  - Design and in vitro performance testing of multiple air classifier technology in
      a new disposable inhaler concept (Twincer) for high powder doses.
AB  - Dry powder inhalation of antibiotics in cystic fibrosis (CF) therapy may be a
      valuable alternative for wet nebulisation, because it saves time and it improves
      lung deposition. In this study, it is shown that the use of multiple air
      classifier technology enables effective dispersion of large amounts of micronised
      powder (up to 25mg). X(50)-values of the aerosol from laser diffraction analysis
      obtained with the Twincer disposable inhaler concept (containing multiple air
      classifier technology) are practically the same as that for the pure drug in the
      range of dose weights between 0 and 25mg. Only for the highest dose weights, a
      minor fraction (5-7.5%) of small agglomerates (5-15microm) is released from the
      inhaler. Moreover, the size distribution of the aerosol is practically the same
      at 1 and 4kPa. Cascade impactor results confirm the good performance of the
      multiple classifier concept. Unprocessed micronised particles or soft spherical
      agglomerates can be used, and special particle engineering processes are not
      necessary. Only a minor fraction of coarse sweeper crystals in the formulation is
      desired to reduce the total inhaler losses for colistin sulfomethate to less than
      5-6% at 4kPa. The classifiers can be designed to retain these crystals with more
      than 95% efficiency.

PMID- 16650740
TI  - [Iatrogenic rectal perforation in a newborn].

PMID- 16650741
TI  - Implementing tutoring strategies into a patient simulator for clinical reasoning
      learning.
AB  - OBJECTIVE: This paper describes an approach for developing intelligent tutoring
      systems (ITS) for teaching clinical reasoning. MATERIALS AND METHODS: Our
      approach to ITS for clinical reasoning uses a novel hybrid knowledge
      representation for the pedagogic model, combining finite state machines to model
      different phases in the diagnostic process, production rules to model triggering
      conditions for feedback in different phases, temporal logic to express triggering
      conditions based upon past states of the student's problem solving trace, and
      finite state machines to model feedback dialogues between the student and
      TeachMed. The expert model is represented by an influence diagram capturing the
      relationship between evidence and hypotheses related to a clinical case. RESULTS:
      This approach is implemented into TeachMed, a patient simulator we are developing
      to support clinical reasoning learning for a problem-based learning medical
      curriculum at our institution; we demonstrate some scenarios of tutoring feedback
      generated using this approach. CONCLUSION: Each of the knowledge representation
      formalisms that we use has already been proven successful in different
      applications of artificial intelligence and software engineering, but their
      integration into a coherent pedagogic model as we propose is unique. The examples
      we discuss illustrate the effectiveness of this approach, making it promising for
      the development of complex ITS, not only for clinical reasoning learning, but
      potentially for other domains as well.

PMID- 16650742
TI  - Aggressive prenatal care results in successful fetal outcomes in CF women.
AB  - BACKGROUND: The impact of pre-pregnancy pulmonary and nutritional status in
      pregnancy outcomes of women with cystic fibrosis (CF) is not clearly defined.
      METHODS: A chart review of CF women who attended the University of Washington
      Medical Center (UWMC), Seattle WA. from January 1989 until May 2004. RESULTS:
      There were 43 pregnancies resulting in 36 live births among 25 of 189 CF women.
      In the subset of CF women receiving their obstetric care at the UWMC whose FEV1
      was < 50% predicted, infant weight was lower than in women with a higher FEV1
      (2.9 kg+/-0.4 (range 2.2-3.3 kg) versus 3.4+/-0.8 kg (range 2.5-5.1 kg)) p = 0.05
      although the gestational ages were the same (37+/-2 weeks (range 33-39 weeks)
      versus to 38+/-2 weeks (range 35-40 weeks) p = 0.17). Infant weight and
      gestational age of women whose initial BMI was < 20 kg/m2 was no different from
      women with a normal initial BMI (3.0+/-0.4 kg, range 2.2-3.4 kg versus 3.3+/-0.8
      kg, range 2.6-5.1 kg p = 0.29, and 37.7+/-2.4 weeks, range 33-39 weeks versus
      37.2+/-2.1 weeks, range 34-40 weeks). CONCLUSIONS: CF women with severe pulmonary
      impairment tend to have lower weight babies but it remains difficult to determine
      prospectively which CF women will tolerate pregnancy well. Aggressive antepartum
      management is recommended for all CF women.

PMID- 16650744
TI  - Temocillin in the treatment of Burkholderia cepacia infection in cystic fibrosis.
AB  - BACKGROUND: Infections due to Burkholderia cepacia complex (Bcc) strains increase
      morbidity and mortality in cystic fibrosis (CF). Some transplant centres reject
      Bcc infected patients. We reviewed the results in patients treated with i.v
      temocillin. METHODS: Twenty-three patients who received 38 courses of temocillin
      (1988-1998) were identified from the CF database at Royal Brompton Hospital. In
      three patients' data were inadequate; therefore analysis was done in 20. Outcome
      was measured as improvement, deterioration or no change (compared to admission)
      in the following categories: clinical (temperature, dyspnoea, sputum volume,
      chest pain), physiological (FEV1, FVC, oxygen saturation) and inflammatory
      markers (WBC, ESR, CRP). Patients who improved in two categories were classified
      as having improved. Antibiotic sensitivities and outcome were recorded. RESULTS:
      In 18 of 32 courses (56.25%) improvement occurred. The organism (Bcc) in eight
      patients' sputum became resistant (three died). The antibiotics was changed in
      five patients with Bcc strains sensitive to temocillin because of no improvement
      and one patient due to allergy (rash). The average time to the next i.v
      antibiotic was 41 days. Eight patients died (in three the Bcc strain was
      resistant to temocillin). Fourteen patients with Bcc were transplanted and eight
      patients survived. Another patient who developed Bcc infection post-operatively,
      failing to respond to temocillin. CONCLUSIONS: These results suggest the
      potential benefit of i.v temocillin in CF patients with Bcc for exacerbations and
      at the time of transplantation.

PMID- 16650745
TI  - Vitamin A and lung function in CF.
AB  - Laboratory evidence suggests that vitamin A could have a protective effect on
      respiratory status in patients with cystic fibrosis (CF). This study shows a
      significant correlation between serum vitamin A concentrations and every aspect
      of lung function tested in 38 patients with stable CF. Serum vitamin D and
      vitamin E concentrations were also measured but did not show any significant
      correlations with lung function.

PMID- 16650746
TI  - WITHDRAWN:2',4',7-Trihydroxyisoflavon (THF) inhibits heat-shock-induced matrix
      metalloproteinase-1 expression in human dermal fibroblasts.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16650747
TI  - Conjugated linoleic acid enhances transepithelial calcium transport in human
      intestinal-like Caco-2 cells: an insight into molecular changes.
AB  - Conjugated linoleic acid (CLA) has been shown to enhance paracellular and
      transcellular Ca transport across human intestinal-like Caco-2 cell monolayers.
      The mechanisms of action, however, are still unclear. Therefore, this study
      investigated the molecular mechanisms underlying CLA-induced stimulation of Ca
      transport by use of preliminary microarray data together with more detailed and
      comprehensive quantitative reverse transcriptase-PCR analysis. While molecular
      expression of junctional adhesion molecule (JAM), ZO-2, ZO-3, claudin 2 and
      claudin 3 were unaltered, ZO-1, occludin, and claudin 4 were all up-regulated
      (1.6, 1.6, 2.4-fold, respectively; P<0.001-0.01) and claudin 1 down-regulated
      (2.5-fold; P<0.05) by trans-10, cis-12 CLA, which may underpin its effects on
      tight-junction function and paracellular Ca transport. On the other hand,
      expression of key genes involved in transcellular Ca transport (CaT1, ECaC1,
      calbindin D(9k), vitamin D receptor and PMCA) were unaffected by trans-10, cis-12
      CLA. The mechanism by which CLA enhances transcellular Ca transport remains
      unclear.

PMID- 16650748
TI  - Regulating the licensing of DNA replication origins in metazoa.
AB  - Eukaryotic DNA replication is a highly conserved process; the proteins and
      sequence of events that replicate animal genomes are remarkably similar to those
      that replicate yeast genomes. Moreover, the assembly of prereplication complexes
      at DNA replication origins ('DNA licensing') is regulated in all eukaryotes so
      that no origin fires more than once in a single cell cycle. And yet there are
      significant differences between species both in the selection of replication
      origins and in the way in which these origins are licensed to operate. Moreover,
      these differences impart advantages to multicellular animals and plants that
      facilitate their development, such as better control over endoreduplication,
      flexibility in origin selection, and discrimination between quiescent and
      proliferative states.

PMID- 16650749
TI  - Cellular memory and dynamic regulation of polycomb group proteins.
AB  - Epigenetic components drive the inheritance of transcriptional programs. This
      cellular memory is crucial for the stable maintenance of cell fates throughout
      development. Polycomb group (PcG) proteins are central players in various
      epigenetic phenomena, such as the maintenance of Hox expression patterns from
      fruit flies to humans, X chromosome inactivation and imprinting in mammals. This
      cellular memory system involves changes at the chromatin level, through histone
      modifications and DNA methylation, as well as at the level of the nuclear
      architecture. Surprisingly, in addition to their role in the stable maintenance
      of repressive states, PcG factors are involved in more dynamic processes such as
      cellular proliferation and plasticity.

PMID- 16650750
TI  - Folate and long-chain polyunsaturated fatty acids in psychiatric disease.
AB  - Schizophrenia, autism and depression do not inherit by Mendel's law, and the
      search for a genetic basis seems unsuccessful. Schizophrenia and autism relate to
      low birth weight and pregnancy complications, which are associated with
      developmental adaptations by "programming". Epigenetics might constitute the
      basis of programming and depend on folate status and one-carbon metabolism in
      general. Early folate status of patients with schizophrenia might be compromised
      as suggested by (i) coinciding incidences of schizophrenia and neural tube
      defects (NTDs) in the Dutch hunger winter, (ii) coinciding seasonal fluctuations
      in birth of patients with schizophrenia and NTDs, (iii) higher schizophrenia
      incidence in immigrants and (iv) higher incidence in methylene tetrahydrofolate
      reductase 677C-->T homozygotes. Recent studies in schizophrenia and autism point
      at epigenetic silencing of critical genes or chromosomal loci. The long-chain
      polyunsaturated fatty acids (LCPUFA), arachidonic acid (AA, from meat) and
      docosahexaenoic acid (fish) are components of brain phospholipids and modulators
      of signal transduction and gene expression. Patients with schizophrenia and,
      possibly, autism exhibit abnormal phospholipid metabolism that might cause local
      AA depletion and impaired eicosanoid-mediated signal transduction. National fish
      intakes relate inversely with major and postpartum depressions. Five out of six
      randomized controlled trials with eicosapentaenoic acid (fish) have shown
      positive effects in schizophrenia, and 4 of 6 were favorable in depression and
      bipolar disorders. We conclude that folate and LCPUFA might be important in both
      the etiology and severity of at least some psychiatric diseases.

PMID- 16650751
TI  - Effects of arachidonic acid, docosahexaenoic acid, prostaglandin E(2) and
      parathyroid hormone on osteoprotegerin and RANKL secretion by MC3T3-E1 osteoblast
      like cells.
AB  - Bone is continuously remodeled through resorption by osteoclasts and the
      subsequent synthesis of the bone matrix by osteoblasts. Cell-to-cell contact
      between osteoblasts and osteoclast precursors is required for osteoclast
      formation. RANKL (receptor activator of nuclear factor-kappaB ligand) expressed
      on osteoblastic cell membranes stimulates osteoclastogenesis, while
      osteoprotegerin (OPG) secreted by osteoblasts inhibits osteoclastogenesis.
      Although polyunsaturated fatty acids (PUFAs) have been implicated in bone
      homeostasis, the effects thereof on OPG and RANKL secretion have not been
      investigated. MC3T3-E1 osteoblasts were exposed to the n-6 PUFA arachidonic acid
      (AA) and the n-3 PUFA docosahexaenoic acid (DHA); furthermore, the bone-active
      hormone parathyroid hormone (PTH) and the effects thereof were tested on OPG and
      RANKL secretion. Prostaglandin E(2) (PGE(2)), a product of AA metabolism that was
      previously implicated in bone homeostasis, was included in the study. AA (5.0-20
      microg/ml) inhibited OPG secretion by 25-30%, which was attenuated by
      pretreatment with the cyclooxygenase blocker indomethacin, suggesting that the
      inhibitory effect of AA on OPG could possibly be PGE(2)-mediated. MC3T3-E1 cells
      secreted very low basal levels of RANKL, but AA stimulated RANKL secretion,
      thereby decreasing the OPG/RANKL ratio. DHA suppressed OPG secretion to a smaller
      extent than AA. This could, however, be due to endogenous PGE(2) production. No
      RANKL could be detected after exposing the MC3T3-E1 cells to DHA. PTH did not
      affect OPG secretion, but stimulated RANKL secretion. This study demonstrates
      that AA and PTH reduce the OPG/RANKL ratio and may increase osteoclastogenesis.
      DHA, however, had no significant effect on OPG or RANKL in this model.

PMID- 16650752
TI  - Biological effects of conjugated linoleic acids in health and disease.
AB  - Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers
      of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef,
      lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9,
      trans-11 (c9t11) isomer. Commercially available CLA is usually a 1:1 mixture of
      c9t11 and trans-10, cis-12 (t10c12) isomers with other isomers as minor
      components. Conjugated LA isomer mixture and c9t11 and t10c12 isomers alone have
      been attributed to provide several health benefits that are largely based on
      animal and in vitro studies. Conjugated LA has been attributed many beneficial
      effects in prevention of atherosclerosis, different types of cancer, hypertension
      and also known to improve immune function. More recent literature with
      availability of purified c9t11 and t10c12 isomers suggests that t10c12 is the
      sole isomer involved in antiadipogenic role of CLA. Other studies in animals and
      cell lines suggest that the two isomers may act similarly or antagonistically to
      alter cellular function and metabolism, and may also act through different
      signaling pathways. The effect of CLA and individual isomers shows considerable
      variation between different strains (BALB/C mice vs. C57BL/6 mice) and species
      (e.g., rats vs. mice). The dramatic effects seen in animal studies have not been
      reflected in some clinical studies. This review comprehensively discusses the
      recent studies on the effects of CLA and individual isomers on body composition,
      cardiovascular disease, bone health, insulin resistance, mediators of
      inflammatory response and different types of cancer, obtained from both in vitro
      and animal studies. This review also discusses the latest available information
      from clinical studies in these areas of research.

PMID- 16650753
TI  - High durability cementitious material with mineral admixtures and carbonation
      curing.
AB  - Nuclear waste repositories need highly durable cementitious materials to function
      for over thousands of years while resisting leaching and degradation. The
      durability of cementitious material can be effectively improved by reducing
      permeability and by changing cement hydrates to a less soluble matrix. This paper
      describes the properties of carbonated new cementitious materials containing
      belite-rich cement and gamma-2CaO.SiO2 as main components. In addition, the long
      term leaching properties are investigated and compared with ordinary Portland
      cement by using a predictive leaching model.

PMID- 16650754
TI  - Genomics for environmental microbiology.
AB  - The utilization of natural microbial diversity in biotechnology is hindered by
      our inability to culture the vast majority of microorganisms and the observation
      that laboratory engineered bacteria rarely function in the wild. It is now clear
      that an understanding of the community structure, function and evolution of
      bacteria in their natural environments is required to meet the promise of
      microbial biotechnology. To meet these new challenges, microbiologists are
      applying the tools of genomics and related high-throughput technologies to both
      cultured microbes and environmental samples. This work will lead to new views on
      ecosystems and biological function together with the biotechnology enabled by
      this science.

PMID- 16650755
TI  - X-inactivation and human disease: X-linked dominant male-lethal disorders.
AB  - X chromosome inactivation (XCI) is the process by which the dosage imbalance of X
      linked genes between XX females and XY males is functionally equalized. XCI
      modulates the phenotype of females carrying mutations in X-linked genes, as
      observed in X-linked dominant male-lethal disorders such as oral-facial-digital
      type I (OFDI) and microphthalmia with linear skin-defects syndromes. The
      remarkable degree of heterogeneity in the XCI pattern among female individuals,
      as revealed by the recently reported XCI profile of the human X chromosome, could
      account for the phenotypic variability observed in these diseases. Furthermore,
      the recent characterization of a murine model for OFDI shows how interspecies
      differences in the XCI pattern between Homo sapiens and Mus musculus result in
      discrepancies between the phenotypes observed in patients and mice.

PMID- 16650756
TI  - X-linked premature ovarian failure: a complex disease.
AB  - Involvement of the X chromosome in premature ovarian failure was demonstrated by
      the relatively frequent chromosomal rearrangements in patients, but the
      requirement of two X chromosomes for ovarian function was quite unexplained until
      recently. Review of the data on chromosomal rearrangements suggests that several
      genes along the X chromosomes contribute to ovarian function. In most instances,
      no single X chromosome gene has a causative role in premature ovarian failure,
      and the phenotype is likely to derive from the additive effect of X-linked and
      non-X-linked factors. Recent data on a small group of balanced X-autosome
      translocations showed that X-linked premature ovarian failure might also be
      caused by a different mechanism, namely position effect of the X chromosome on
      non-X-linked genes, and suggest a peculiar organization of the X chromosome
      during oogenesis.

PMID- 16650757
TI  - Genetics of disease The sex chromosomes and human disease.

PMID- 16650758
TI  - How the gene content of human sex chromosomes evolved.
AB  - The X and Y chromosomes of humans and other mammals both have very atypical gene
      contents. The degenerate Y bears only a handful of genes that are specialized for
      male sex and reproduction. Now it seems that the X over-represents genes
      controlling reproductive traits and intelligence. This is hard to explain in
      terms of function but makes excellent sense in terms of evolution. Comparisons
      between the gene content of the X and Y in humans, distantly related mammals, and
      other vertebrates, define the evolutionary past of our sex chromosomes and
      suggest how special selective forces act on the X and Y.

PMID- 16650759
TI  - Paroxysmal nocturnal hemoglobinuria: an acquired X-linked genetic disease with
      somatic-cell mosaicism.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a severe hemolytic anemia caused by
      an intrinsic abnormality of the red blood cells that makes them exceedingly
      susceptible to the lytic action of activated complement (C). This abnormality
      results from a mutation in the PIG-A gene on Xp22. Given that the mutation is not
      inherited but is somatically acquired by a hematopoietic stem cell, it creates
      two populations of blood cells: normal cells and PNH cells. The clinical
      expression of PNH depends on the relative and absolute expansion of the PNH cell
      population, which probably depends, in turn, on a paradoxical growth advantage
      conferred to it by the existence in the patients of an autoimmune process that
      exerts negative selection against the 'normal' hematopoietic stem cells.

PMID- 16650760
TI  - The sequences of the human sex chromosomes.
AB  - The sequences of both of the human sex chromosomes and of a substantial part of
      the chimpanzee Y chromosome have now been determined, and most of the protein
      coding genes have been identified. The X chromosome codes for more than 800
      proteins but the Y chromosome for only approximately 60, illustrating their very
      different evolutionary histories since their origin from an autosomal pair
      approximately 300 million years ago and explaining their differential importance
      in disease. These sequences have provided the basis for understanding normal
      patterns of variation, such as the distribution of SNPs, and patterns of linkage
      disequilibrium. In addition, they have been useful for identifying variants
      associated with simple Mendelian disorders such as microphthalmia or mental
      retardation, and more complex disorders such as osteoporosis.

PMID- 16650761
TI  - The human Y chromosome: a masculine chromosome.
AB  - Once considered to be a genetic wasteland of no scientific interest beyond sex
      determination, the human Y chromosome has made a significant comeback in the past
      few decades and is currently implicated in multiple diseases, including
      spermatogenic failure - absent or very low levels of sperm production. The Y
      chromosome contains over one hundred testis-specific transcripts, and several
      deletions have been described that remove some of these transcripts, thereby
      causing spermatogenic failure. Screening for such deletions in infertile men is
      now a standard part of clinical evaluation. Many other Y-chromosome structural
      variants, some of which affect gene copy number, have been reported recently, and
      future research will be necessary to address the phenotypic effect of these
      structural variants.

PMID- 16650762
TI  - Synthesis and SAR of 1,3-disubstituted cyclohexylmethyl urea and amide
      derivatives as non-peptidic motilin receptor antagonists.
AB  - A series of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives were
      synthesized as motilin receptor antagonists. Starting from known motilin
      antagonists, 1a and 1b, the cyclopentene scaffold was replaced and the four
      recognition elements optimized to arrive at a potent novel series.

PMID- 16650763
TI  - Privileged structure based ligands for melanocortin-4 receptors--aliphatic
      piperazine derivatives.
AB  - Aliphatic carbocyclic replacement of the benzyl group of compound 1 yielded
      compounds with high affinity for the melanocortin-4 receptor (MC4R). Compounds
      with a cyclohexyl group showed a consistent high affinity, while different polar
      groups with less basicity were good replacements for the original diethyl amines.
      Substitution of the polar group found in these privileged structures with an
      aliphatic moiety produced compounds with high affinity for MC4R.

PMID- 16650764
TI  - Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships
      of N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides.
AB  - Substituted N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides were
      investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity
      relationship patterns for this class of compounds are discussed.

PMID- 16650765
TI  - Changing control strategies during standard assessment using computerized dynamic
      posturography with older women.
AB  - The goal of this investigation was to explore the use of spectral analysis to
      examine the data obtained during computerized dynamic posturography (CDP). In
      particular, we examined whether spectral analysis would provide more detailed
      information about underlying postural control strategies and potential learning
      across conditions and trials of the sensory organization test (SOT). Twenty older
      women between the ages of 60 and 72 (mean=65.2) were assessed using standard
      testing protocol. Participants showed significant improvements from the first to
      the second trials in their equilibrium scores in the more difficult conditions.
      This finding was reflected in the spectral analysis data by a shift in the
      frequency distribution towards greater power in the lower frequency range. This
      frequency change likely reflects a change in the ankle strategy used to maintain
      balance during the more difficult conditions.

PMID- 16650766
TI  - Dual-task-related gait changes in individuals with stroke.
AB  - Many daily activities require people to complete a motor task while walking. The
      purpose of this study was to analyze subjects' ability to perform motor tasks
      while walking. Subjects were classified into three different groups. The first
      group included 15 full community ambulators post-stroke. The second group
      included 15 least limited community ambulators post-stroke. The final group
      included 15 age-matched healthy subjects. Gait performance was measured under
      three different conditions: (1) preferred walking (single task); (2) walking
      buttoning up (buttoning task); (3) walking while carrying a tray with glasses
      (tray-carrying task). Gait velocity, cadence, stride time, stride length,
      temporal and spatial symmetry indices were examined with the GAITRite system. Our
      results showed that there were no significant differences between full community
      ambulators and control subjects for all gait variables. However, there were
      significant differences in dual-task-related gait decrement between the full
      community ambulators and control subjects. There were also significant
      differences in dual-task-related gait decrement between least limited community
      ambulators and control subjects. The findings of this study suggest that subjects
      with stroke including the full community ambulators have difficulty performing
      two motor tasks concurrently.

PMID- 16650767
TI  - Novel ketoconazole analogues based on the replacement of 2,4-dichlorophenyl group
      with 1,4-benzothiazine moiety: design, synthesis, and microbiological evaluation.
AB  - As a part of a program to develop novel antifungal agents, new compounds which
      incorporate the 1,4-benzothiazine moiety into the structure of ketoconazole (KTZ)
      were prepared. These compounds were computationally investigated to assess
      whether the 1,4-benzothiazine moiety was a suitable bioisosteric replacement for
      the 2,4-dichlorophenyl group of KTZ in order to obtain a more potent inhibition
      of CYP51 enzyme of Candida albicans. Results of preliminary microbiological
      studies show that the racemic cis-7 analogue has a good in vivo activity,
      comparable to that of KTZ, but the best activity was observed in the racemic
      trans-7 analogue.

PMID- 16650768
TI  - Volume-weighted mean volume of the submandibular gland acini in male and female
      diabetic rats.
AB  - Mouth dryness is one of the complications of diabetes mellitus but there has been
      little work on morphological changes of the salivary glands. In the present
      study, the effects of diabetes mellitus on the serous and mucous acini of
      submandibular gland of male and female rats, 4 and 12 weeks after diabetes
      induction were studied. Male and female rats were divided into experimental and
      control subgroups. Diabetes was induced to experimental rats by streptozotocin.
      At the end of 4 and 12 weeks, the submandibular glands were removed, random
      sections obtained and volume-weighted mean acini volume was estimated by point
      sampled intercepts method. The data revealed that volume reduction occurred only
      in serous acini in both male and female rats 12 weeks after diabetes induction
      and the others remained unchanged. The present research using stereological
      methods demonstrates that diabetes make some morphological changes in serous
      acini, the main exocrine part of the rat submandibular gland.

PMID- 16650769
TI  - Abscisic acid promotes accumulation of toxin ODAP in relation to free spermine
      level in grass pea seedlings (Lathyrus sativus L.).
AB  - Interrelationship among abscisic acid (ABA) content, accumulation of free
      polyamines and biosynthesis of beta-N-oxalyl-l-alpha,beta-diaminopropionic acid
      (ODAP) was studied in grass pea (Lathyrus sativus L.) seedlings under drought
      stress induced by 10% polyethylene glycol (PEG6000). Increase of ABA content
      occurred prior to that of ODAP and polyamine contents, and was found
      significantly positive correlation between ABA content and ODAP content. Addition
      of exogenous ABA increased ODAP content in leaves. On the other hand,
      pretreatment with alpha-difluoromethylarginine (DFMA), a polyamine biosynthesis
      inhibitor, significantly suppressed the accumulation of free putrescine (Put),
      free spermidine (Spd) and free spermine (Spm), which in turn inhibited
      biosynthesis of ODAP in well-watered leaves. Meanwhile, addition of exogenous Put
      alleviated DFMA-induced inhibition on the biosynthesis of Put and Spd, but did
      not affect the biosynthesis of Spm and ODAP in well-watered leaves. Same result
      was also achieved in drought-stressed leaves. Increasing accumulation of ODAP was
      significantly correlated with increasing Spm content (R=0.7957**) but not with
      that of Spd and Put. Therefore, it can be argued that ABA stimulated the
      biosynthesis of ODAP simultaneously with increasing the level of free Spm under
      drought stress condition.

PMID- 16650770
TI  - Isoflavonoids are present in Arabidopsis thaliana despite the absence of any
      homologue to known isoflavonoid synthases.
AB  - Extracts from Arabidopsis thaliana leaves and inflorescence stalks and from
      Lepidium sativa (Brassicaceae) seedlings were analysed by HPLC-MS-SIM and by five
      isoflavonoid-specific ELISA methods after the HPLC fractionation of samples, in
      order to determine presence of isoflavonoids. Individual ELISAs were specific for
      daidzein, genistein, biochanin A and for their derivatives substituted either at
      the 4'- or at the 7- positions. Both analytical approaches revealed homologous
      spectra of isoflavonoids in both plant species. As the ononin specific
      immunoassay was not available this compound was only detected by HPLC-MS.
      Formononetin and prunetin represented the main aglycones followed by biochanin A,
      daidzein and genistein; sissotrin was the most abundant isoflavonoid glycoside
      followed by ononin, daidzin and genistin. The content of individual compounds
      ranged from a few micrograms up to 2.2 mg kg(-1) (dry weight). Expression
      profiles of A. thaliana genes homologous to enzymes involved in isoflavonoid
      synthesis and metabolism were extracted from publicly available transcriptomic
      datasets for various tissues. Genes likely to be involved in important steps of
      the isoflavonoid metabolism in A. thaliana were identified. However, in accord
      with the previously published data, no homologue to isoflavone synthases known
      from the Fabaceae plants was found. These aryl migrating enzymes belong to the
      CYP93C family that is absent in A. thaliana. We conclude that another gene must
      be responsible for biosynthesis of the isoflavone skeleton in Brassicaceae.

PMID- 16650771
TI  - Vaccine-derived polioviruses.
AB  - The Sabin oral poliovaccine (OPV) is extremely efficacious and safe, despite its
      inherent genetic instability. While reversion to nearly wild-type phenotype
      regularly occurs soon after the onset of OPV reproduction in the gastro
      intestinal tract of vaccine recipients or their contacts, this is usually not a
      big problem, provided the vaccine is used either for mass vaccination or in
      populations with a relatively high level of anti-polio immunity. However, if
      these conditions are not met, the vaccine viruses are likely to be converted into
      highly transmissible agents with a nearly wild-type level of neurovirulence.
      Moreover, OPV viruses may persist and evolve even in adequately immunized
      populations. The current strategy for the "endgame" of poliovirus eradication
      envisions cessation of OPV usage shortly after the last isolation of a wild
      poliovirus. If implemented, this strategy would result in rapid growth of non
      immune human populations at the time when OPV derivatives would very likely be
      persisting. Therefore, the planned cessation of OPV vaccination is associated
      with a very high, and in the author's opinion, unacceptable risk of polio
      outbreaks caused by OPV derivatives. The only currently available tool to curb
      such outbreaks is OPV, which should have been used at a global scale. Safe
      discontinuation of OPV vaccination will be possible only after an efficient new
      vaccine or an anti-poliovirus drug is available. To achieve this goal,
      stimulation of poliovirus research and elimination of organizational and
      financial obstacles preventing it are needed.

PMID- 16650772
TI  - Vaccine-derived poliovirus from long term excretors and the end game of polio
      eradication.
AB  - Seven cases of long-term poliovirus excretion in the UK and Ireland are reviewed
      in this paper. They include a rare case of long-term virus excretion by a healthy
      child recently found in Ireland and the case with the longest period of vaccine
      derived poliovirus excretion by an immunodeficient individual ever known, 18
      years. The evolution of viral properties such as antigenic structure,
      neurovirulence, sensitivity for growth at high temperatures, and differences in
      nucleotide sequence from the Sabin vaccine strains were studied in detail. The
      relevance of these cases in the context of the global polio eradication
      initiative and the design of vaccination strategies for the last stages of
      eradication and the post-eradication era are discussed.

PMID- 16650773
TI  - Technology transfer of Sabin-IPV to new developing country markets.
AB  - The Netherlands Vaccine Institute (NVI) developed the micro-carrier technology
      for large-scale production of IPV in the late 1960s and has used this technology
      successfully to produce IPV as well as DTP-IPV for the national immunization
      program in the Netherlands. As a public sector organization, and as one of the
      Millennium Development Goals, NVI has supported over the years access to vaccine
      technology like DTP and Hib for vaccine manufacturers in developing countries. In
      line with this role as a resource institute, NVI has recently been approached by
      a number of vaccine manufacturers, predominantly from developing countries, for
      transfer of IPV technology to meet the anticipated increase in demand for IPV
      following OPV cessation. Since WHO encourages new manufacturers to use the
      attenuated Sabin virus instead of wild polio strains in the production of IPV,
      NVI decided to respond positively to this WHO policy. The existing NVI experience
      in large-scale production of IPV and OPV using Vero cell based micro-carrier
      technology and its experience with experimental Sabin-IPV is an attractive start
      for the development of Sabin-IPV. This paper discusses the approach followed and
      the experience already gained in the project, as well as factors critical to its
      success.

PMID- 16650774
TI  - High resolution scanning tunnelling microscopy of the beta-amyloid protein
      (Abeta1-40) of Alzheimer's disease suggests a novel mechanism of oligomer
      assembly.
AB  - The aggregation of the beta-amyloid protein (Abeta) is an important step in the
      pathogenesis of Alzheimer's disease. There is increasing evidence that lower
      molecular weight oligomeric forms of Abeta may be the most toxic species in vivo.
      However, little is known about the structure of Abeta oligomers. In this study,
      scanning tunnelling microscopy (STM) was used to examine the structure of Abeta
      monomers, dimers and oligomers. Abeta1-40 was visualised by STM on a surface of
      atomically flat gold. At low concentrations (0.5 microM) small globular
      structures were observed. High resolution STM of these structures revealed them
      to be monomers of Abeta. The monomers measured approximately 3-4 nm in diameter.
      Internal structure was seen in many of the monomers consistent with a
      conformation in which the polypeptide chain is folded into 3 or 4 domains.
      Oligomers were seen after ageing the Abeta solution for 24 h. The oligomers were
      also 3-4 nm in width and appeared to be formed by the end-to-end association of
      monomers with the polypeptide chain oriented at 90 degrees to the axis of the
      oligomer. The results suggest that the oligomer formation can proceed through a
      mechanism involving the linear association of monomers.

PMID- 16650775
TI  - Acute tryptophan depletion improves performance and modulates the BOLD response
      during a Stroop task in healthy females.
AB  - To gain more insight into the effect of low brain serotonin (5-HT) on brain
      activation related to conflict, the present study examined the effect of acute
      tryptophan depletion (ATD) on performance and the blood oxygen level dependent
      (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen
      healthy female volunteers were tested during a placebo and tryptophan depletion
      session in an event-related fMRI design. ATD improved performance during Stroop
      interference. Two effects of ATD on the BOLD response were found. Firstly, ATD
      increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when
      incongruent color words were compared with congruent color words in the first
      Stroop block the participants performed. Secondly, ATD increased the BOLD
      response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color
      words. ATD did not affect the BOLD response accompanying emotional stimuli.
      However, we showed that ATD increased the interference of negative words on color
      naming. This finding was explained in terms of an emotional processing bias in
      favor of negative words, which leads to stronger interference of these words. In
      line with previous studies, the present study showed that a temporary reduction
      of 5-HT improved Stroop performance and changed the underlying brain activation
      pattern in healthy female participants. Moreover, we replicated our previous
      finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex
      during tasks that require cognitive control.

PMID- 16650776
TI  - Early macrophage MRI of inflammatory lesions predicts lesion severity and disease
      development in relapsing EAE.
AB  - Magnetic resonance imaging (MRI) is of great utility in diagnosis and monitoring
      of multiple sclerosis (MS). Axonal loss is considered the main cause of
      accumulating irreversible disability. MRI using ultrasmall-super-paramagnetic
      iron-oxide (USPIO) nanoparticles is a new technique to disclose in vivo central
      nervous system (CNS) inflammatory lesions infiltrated by macrophages in
      experimental autoimmune encephalomyelitis (EAE). Here, we raised the question of
      whether USPIO-enhanced MRI could serve as a tool to predict disease severity. We
      investigated, in a relapsing EAE model with various degrees of disease severity,
      the interindividual differences at the beginning of CNS inflammation as revealed
      in vivo by MRI with USPIO in correlation to the severity of both acute and
      chronic tissue damage including axonal loss. At the onset of the disease,
      observation of MRI alterations with USPIO allowed assignment of animals into
      USPIO+ and USPIO- groups. In 54.5% of diseased rats, MRI with USPIO+ at first
      attack revealed signal abnormalities mainly localized in the brainstem and
      cerebellum. Although animals did not present any clinically significant
      differences during the first attack, USPIO+ rats presented significantly more
      important tissue alterations at the first attack (onset and initiated recovery
      phase) and, at the second attack, more severe clinical disease with axonal loss
      compared to USPIO- rats. MRI lesion load and volume at the first attack correlate
      significantly with inflammation, macrophage recruitment, demyelination, acute
      axonal damage and, at the second attack, extent of axonal loss. This new MRI
      application of in vivo monitoring of macrophage infiltration provides a new
      platform to investigate the severity of inflammatory demyelinating CNS diseases.

PMID- 16650777
TI  - Time-resolved fMRI of mental rotation revisited--dissociating visual perception
      from mental rotation in female subjects.
AB  - Functional neuroimaging studies have demonstrated that mental rotation paradigms
      activate a network of spatially distributed cortical areas rather than a discrete
      brain region. Although the neuro-anatomical nodes of the rotation network are
      well established, their specific functional role is less well identified. It was
      the aim of the present study to dissociate network components involved in the
      visual perception of 3D cubic objects from regions involved in their mental
      spatial transformation. This was achieved by desynchronizing the time course of
      the perceptional process (i.e., stimulus duration) from the duration of the
      cognitive process (i.e., reaction times) and by comparing these with the temporal
      characteristics of the hemodynamic response functions (HRFs) in regions of
      interest. To minimize intersubject variability, an all-female subject group was
      chosen for this investigation. Time-resolved fMRI analysis revealed a significant
      increase in the full width at half maximum (FWHM) of the HRF with reaction times
      in the supplementary motor area (pre-SMA), in the bilateral premotor cortex (PMd
      proper), and in the left parietal lobe (PP). The FWHM in visual system components
      such as the bilateral lateral occipital complex (LOC) and dorsal extrastriate
      visual areas (DE) was constant across trials and roughly equal to the stimulus
      duration. These findings suggest that visual system activation during mental
      rotation reflects visual perception and can be dissociated from other network
      components whose response characteristics indicates an involvement in the mental
      spatial transformation itself.

PMID- 16650778
TI  - Anatomically informed interpolation of fMRI data on the cortical surface.
AB  - Analyzing functional magnetic resonance imaging (fMRI) data restricted to the
      cortical surface is of particular interest for two reasons: (1) to increase
      detection sensitivity using anatomical constraints and (2) to compare or use fMRI
      results in the context of source localization from magneto/electro
      encephalography (MEEG) data, which requires data to be projected on the same
      spatial support. Designing an optimal scheme to interpolate fMRI raw data or
      resulting activation maps on the cortical surface relies on a trade-off between
      choosing large enough interpolation kernels, because of the distributed nature of
      the hemodynamic response, and avoiding mixing data issued from different
      anatomical structures. We propose an original method that automatically adjusts
      the level of such a trade-off, by defining interpolation kernels around each
      vertex of the cortical surface using a geodesic Voronoi diagram. This Voronoi
      based interpolation method was evaluated using simulated fMRI activation maps,
      manually generated on an anatomical MRI, and compared with a more standard
      approach where interpolation kernels were defined as local spheres of radius r=3
      or 5 mm. Several validation parameters were considered: the spatial resolution of
      the simulated activation map, the spatial resolution of the cortical mesh, the
      level of anatomical/functional data misregistration and the location of the
      vertices within the gray matter ribbon. Using an activation map at the spatial
      resolution of standard fMRI data, robustness to misregistration errors was
      observed for both methods, whereas only the Voronoi-based approach was
      insensitive to the position of the vertices within the gray matter ribbon.

PMID- 16650779
TI  - Functional EEG topography in sleep and waking: state-dependent and state
      independent features.
AB  - Power spectra in the non-rapid eye movement sleep (NREMS) electroencephalogram
      (EEG) have been shown to exhibit frequency-specific topographic features that may
      point to functional differences in brain regions. Here, we extend the analysis to
      rapid eye movement sleep (REMS) and waking (W) to determine the extent to which
      EEG topography is determined by state under two different levels of sleep
      pressure. Multichannel EEG recordings were obtained from young men during a
      baseline night, a 40-h waking period, and a recovery night. Sleep deprivation
      enhanced EEG power in the low-frequency range (1-8 Hz) in all three vigilance
      states. In NREMS, the effect was largest in the delta band, in W, in the theta
      band, while in REMS, there was a peak in both the delta and the theta band. The
      response of REMS to prolonged waking and its pattern of EEG topography was
      intermediate between NREMS and W. Cluster analysis revealed a major topographic
      segregation into three frequency bands (1-8 Hz, 9-15 Hz, 16-24 Hz), which was
      largely independent of state and sleep pressure. To assess individual topographic
      traits within each state, the differences between pairs of power maps were
      compared within (i.e., for baseline and recovery) and between individuals (i.e.,
      separately for baseline and recovery). A high degree of intraindividual
      correspondence of the power maps was observed. The frequency-specific clustering
      of power maps suggests that distinct generators underlie EEG frequency bands.
      Although EEG power is modulated by state and sleep pressure, basic topographic
      features appear to be state-independent.

PMID- 16650780
TI  - A new method for fast quantitative mapping of absolute water content in vivo.
AB  - The presence of brain edema, in its various forms, is an accompanying feature of
      many diseased states. Although the localized occurrence of brain edema may be
      demonstrated with MRI, the quantitative determination of absolute water content,
      an aspect that could play an important role in the objective evaluation of the
      dynamics of brain edema and the monitoring of the efficiency of treatment, is
      much more demanding. We present a method for the localized and quantitative
      measurement of absolute water content based on the combination of two fast multi
      slice and multi-time point sequences QUTE and TAPIR for mapping the T(2)* and
      T(1) relaxation times, respectively. Incorporation of corrections for local B(1)
      field miscalibrations, temperature differences between the subject and a
      reference probe placed in the FOV, receiver profile inhomogeneities and T(1)
      saturation effects are included and allow the determination of water content with
      anatomical resolution and a precision >98%. The method was validated in phantom
      studies and was applied to the localized in vivo measurement of water content in
      a group of normal individuals and a patient with brain tumor. The results
      demonstrate that in vivo measurement of regional absolute water content is
      possible in clinically relevant measurement times with a statistical and
      systematic measurement error of <2%.

PMID- 16650781
TI  - Enzyme-linked immunosorbent assay of a linear, recombinant peptide designed for
      immunotherapy of Japanese cedar pollinosis.
AB  - INTRODUCTION: Cry-consensus peptide, a recombinant T-cell epitope peptide for
      immunotherapy of Japanese cedar pollinosis, is a linear peptide that does not
      have disulfide bonds because no cysteine residue exists in the molecule. We
      examined whether a sandwich enzyme-linked immunosorbent assay (ELISA) could be
      performed for linear peptides such as Cry-consensus peptide. METHODS: The 3
      dimensional conformation of Cry-consensus peptide was examined by (1)H NMR
      analysis. Nineteen monoclonal antibodies (mAbs) that recognized various domains
      of Cry-consensus peptide were established to use in a sandwich ELISA. The
      relationship between the recognition sites of mAbs and the sensitivity of the
      ELISA was investigated to optimize the selection of the combination of the
      capture and the detection antibodies. ELISA inhibitors in serum and plasma were
      also studied to improve the stability and the sensitivity of determination.
      RESULTS: (1)H NMR analysis of Cry-consensus peptide suggested that Cry-consensus
      peptide molecule had no portions with rigid conformation. The sensitivity of the
      ELISA showed a good correlation with the distance between the respective binding
      sites of the capture and the detection antibodies. Human serum albumin and alpha1
      acid glycoprotein strongly inhibited the binding of the capture mAb to Cry
      consensus peptide in a dose-dependent manner, and heparin also inhibited the
      binding in the concentration at which it is used as anticoagulant. Taken
      together, the findings indicated that an optimized method showed good linearity
      and minimal variation from 0 to 1000 ng/ml of Cry-consensus peptide. DISCUSSION:
      These data indicate that this method is useful for monitoring Cry-consensus
      peptide concentrations in plasma or serum.

PMID- 16650782
TI  - A model of orthostatic hypotension in the conscious monkey using lower body
      negative pressure.
AB  - INTRODUCTION: Methods most commonly used for detecting susceptibility to
      orthostatic hypotension in humans include head-up tilt and the application of
      lower body negative pressure (LBNP). The objective of this study was to evaluate
      the use of LBNP for detecting drug-induced changes in susceptibility to
      orthostatic hypotension in conscious monkeys (Macaca fascicularis). METHODS:
      Orthostatic responses were produced using an airtight chamber, which sealed
      around the stomach (umbilical area) and enclosed the lower body, to which were
      applied successive decrements of 10 mmHg chamber pressure every 5 min until the
      orthostatic response was observed. Cardiovascular measurements, involving
      arterial pressures, heart rate, and left ventricular pressures were recorded. The
      hypotensive agents prazosin and minoxidil were administered to evaluate the
      ability of the procedure to detect drug-induced changes in the susceptibility to
      orthostatic hypotension. RESULTS: A rapid decrease in systolic arterial pressure
      of >20 mmHg occurring within a 30 s time period was determined to be the best
      indicator of an orthostatic response. The application of LBNP produced an
      orthostatic response in all monkeys and on all occasions (100% response). The
      onset, rate and magnitude of the decrease in systolic blood pressure were also
      consistent for each monkey. Prazosin (>or=0.16 mg/kg, iv) produced an increase in
      the susceptibility to the orthostatic response, whereas minoxidil (10 mg/kg, po)
      had no effect. These results are consistent with previous findings in humans,
      where similar decreases in arterial pressures occur following the administration
      of prazosin and minoxidil, whereas increased susceptibility to orthostatic
      hypotension only occurs with prazosin. DISCUSSION: The results of this study
      demonstrate that the application of the LBNP is a reliable method for producing
      an orthostatic hypotensive response in conscious monkeys. In addition, the use of
      positive (prazosin) and negative (minoxidil) controls demonstrated that the use
      of LBNP is a valid method for evaluating the effect of drug treatment on
      susceptibility to orthostatic hypotension.

PMID- 16650783
TI  - Exploration in outbred mice covaries with general learning abilities irrespective
      of stress reactivity, emotionality, and physical attributes.
AB  - Across multiple learning tasks (that place different sensory, motor, and
      information processing demands on the animals), we have found that the
      performance of mice is commonly regulated by a single factor ("general learning")
      that accounts for 30-40% of the variance across individuals and tasks.
      Furthermore, individuals' general learning abilities were highly correlated with
      their propensity to engage in exploration in an open field, a behavior that is
      potentially stress-inducing. This relationship between exploration in the open
      field and general learning abilities suggests the possibility that variations in
      stress sensitivity/responsivity or related emotional responses might directly
      influence individuals' general learning abilities. Here, the relationship of
      sensory/motor skills and stress sensitivity/emotionality to animals' general
      learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of
      six learning tasks as well as 21 tests of exploratory behavior, sensory/motor
      function and fitness, emotionality, and stress reactivity. The performances of
      individual mice were correlated across six learning tasks, and the performance
      measures of all learning tasks loaded heavily on a single factor (principal
      component analysis), accounting for 32% of the variability between animals and
      tasks. Open field exploration and seven additional exploratory behaviors
      (including those exhibited in an elevated plus maze) also loaded heavily on this
      same factor, although general activity, sensory/motor responses, physical
      characteristics, and direct measures of fear did not. In a separate experiment,
      serum corticosterone levels of mice were elevated in response to a mild
      environmental stressor (confinement on an elevated platform). Stress-induced
      corticosterone levels were correlated with behavioral fear responses, but were
      unsystematically related to individuals' propensity for exploration. In total,
      these results suggest that although general learning abilities are strongly
      related to individuals' propensity for exploration, this relationship is not
      attributable to variations in sensory/motor function or the individuals'
      physiological or behavioral sensitivity to conditions that promote stress or
      fear.

PMID- 16650784
TI  - Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia.
AB  - The diagnosis of a 14-year-old girl with a new homoallelic mutation in the
      sepiapterin reductase (SR) gene is reported. Initially she presented at the age
      of 2 with hypotonia and mild cognitive developmental delay, and was diagnosed as
      having mild methylmalonic aciduria, which was recently identified as
      methylmalonylCoA racemase deficiency, a new defect in valine-isoleucine
      metabolism. After a 12-year progression of her neurologic condition, which had
      made her wheelchair-bound at the age of 6, dystonia with diurnal variation had
      become apparent. At the age of 14 this finding led to rapid diagnosis of SR
      deficiency. The diagnostic approach with CSF neurotransmitter and pterins
      analysis and combined phenylalanine/BH(4) loading test, and finally measurement
      of sepiapterin in CSF is illustrative for the diagnosis of SR deficiency. As in
      all other patients with this new defect, very low levels of homovanillic acid and
      5-hydroxyindoleacetic acid and high levels of biopterin and sepiapterin in the
      CSF are the diagnostic hallmark. The girl improved dramatically on treatment with
      L-DOPA and 5-hydroxytryptophan. The initial diagnosis of methylmalonic aciduria
      may afterwards be considered to have not significantly contributed to her
      clinical condition and only has led to a long delay of the clinically relevant
      diagnosis of SR deficiency. Although the clinical condition of this recently
      recognized autosomal recessive defect in pterin metabolism is complex and many
      symptoms can occur in variable severity and time of onset, dystonia with diurnal
      variation is a characteristic finding, as shown in nearly all patients described
      so far. The rapid and favourable response on treatment with L-DOPA warrants the
      classification of SR deficiency as another autosomal recessive type of DOPA
      responsive dystonia (DRD). This classification is important to improve the
      awareness of clinicians that more than one metabolic defect can underlie the
      phenotype of a DOPA-responsive dystonic disorder and that dystonia should always
      trigger a rapid diagnosis of the underlying neurotransmitter synthesis defect, in
      view of the excellent treatability of a DRD.

PMID- 16650785
TI  - Deletion of Glu at codon 13 of the TCAP gene encoding the titin-cap-telethonin is
      a rare polymorphism in a large Italian population.

PMID- 16650786
TI  - Plasma histamine concentration and histamine detection in peripheral blood
      eosinophils in cats.
AB  - Plasma histamine levels were measured in 11 clinically healthy cats and 15 cats
      with allergic dermatitis. Histamine levels were markedly elevated in 5/15
      allergic cats. A calcium ionophore, A23187, stimulates histamine release from
      feline peripheral blood cells. Immunostaining of blood smears from clinically
      healthy cats revealed that approximately 10% of eosinophils possessed histamine
      containing granules. These results indicate that some peripheral eosinophils in
      cats contain histamine and can release histamine by appropriate stimulation.

PMID- 16650787
TI  - Klebsiella ozaenae splenic abscess following odontogenic infection in a girl with
      sickle cell disease.

PMID- 16650788
TI  - Kyphoplasty for pregnancy-associated osteoporotic vertebral fractures.
AB  - We report a case of pregnancy-associated osteoporotic vertebral fracture treated
      by kyphoplasty. This case is important for being the first case of postpregnancy
      osteoporotic vertebral fracture treated with kyphoplasty. Although kyphoplasty is
      a very successful procedure in short-term pain relief for osteoporotic vertebral
      fractures, there is a critical need for randomized controlled trials
      demonstrating short-term complications of kyphoplasty including new vertebral
      fractures.

PMID- 16650789
TI  - Cauda equina compression revealing brown tumor of the spine in a long-term
      hemodialysis patient.
AB  - Brown tumors, or osteoclastomas, are erosive bony lesions arising as a
      complication of hyperparathyroidism (HPT). In patients with end-stage renal
      disease (ESRD), brown tumors are classic skeletal manifestations usually seen in
      severe forms of secondary HPT. However, involvement of the spine is considered
      extremely rare. We report a long-term hemodialysis case, in which cauda equina
      compression developed due to a sacral brown tumor. A decompressive surgery and
      subtotal parathyroidectomy were indicated to preserve neurologic function, and to
      ensure remineralization of the lesion. This case illustrates that, though rare,
      brown tumors should be considered in uremic patients with neurological symptoms.
      Emergent decompressive surgery is required to remove pressure on neurological
      structures and to stabilize the spine.

PMID- 16650790
TI  - The use of newly developed real-time PCR for the rapid identification of bacteria
      in culture-negative osteomyelitis.
AB  - We report a case of a culture-negative osteomyelitis in which our newly developed
      real-time polymerase chain reaction (PCR) could differentiate Staphylococcus
      aureus from Staphylococcus epidermidis. This is the first report that described
      the application of this novel assay to an orthopedics clinical sample. This assay
      may be useful for other clinical culture-negative cases in a combination with a
      broad-spectrum assay as a rapid microorganism identification method.

PMID- 16650791
TI  - Three-dimensional Doppler sonographic vascular imaging in regions with increased
      MR enhancement in inflamed wrists of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare three-dimensional (3D) power Doppler ultrasonography (PDUS)
      with contrast enhanced magnetic resonance imaging (MRI) in their capability to
      visualize synovial vascularity in inflamed wrists of patients with rheumatoid
      arthritis (RA). METHODS: Nine patients with RA showing clinically active
      arthritis of the wrist as determined by tenderness and swelling were examined by
      contrast enhanced MRI and 3D PDUS. Vascularity close to and inside the joint
      capsule was visualized by conventional power Doppler mode. In a region with high
      Doppler signal intensity (=region of interest/ROI) a 3D blood vessel tree was
      obtained by a free-hand sweep. 3D images were evaluated with regard to the number
      of blood vessels in the intra- and peri-articular region. MRI examinations were
      performed using a 1.5 T Scanner. In MRI, time resolved coronal contrast enhanced
      T1-weighted sequences with fat suppression were acquired during an 8 min period
      to assess tissue enhancement. Relative enhancement was calculated and compared to
      3D PDUS findings. RESULTS: A 3D vascular tree consisting of peri- and intra
      articular blood vessels could be demonstrated in the same anatomical ROI in which
      an increased gadolinium enhancement was measured by MRI in all examined RA
      patients. The number of penetrating vessels into the joint capsule, the number of
      intra-articular vessels and a semiquantitative estimation of the strength of
      blood flow were used to generate a 3D score for the intensity of synovial
      vascularity. CONCLUSION: When compared with clinical symptoms and the gold
      standard dynamic MRI, 3D PDUS is a reliable imaging technique for assessing
      synovial vascularity in inflamed wrists of RA patients.

PMID- 16650792
TI  - Sonographic evaluation of the tendons in familial Mediterranean fever and
      Behcet's disease.
AB  - OBJECTIVES: There have been some studies on the burden of certain rheumatological
      disorders on the tendons; however, patients with familial Mediterranean fever
      (FMF) and Behcet's disease (BD) have not, up to now, been studied in this regard
      in the literature. Thus, this current study centers on ensuing changes in the
      tendons of these patients. METHODS: The study comprised 32 patients with FMF (13
      male, 19 female), 31 with BD (18 male, 13 female) and 35 control subjects (17
      male, 18 female). Sonographical evaluations were performed from the triceps,
      quadriceps and Achilles tendons on the non-dominant extremities of the
      individuals using a linear array probe of 8-16 MHz. RESULTS: The mean triceps
      tendon (TT) thickness value of FMF patients was greater than that of BD patients
      (P=0.03) or the controls' (P=0.02). The mean quadriceps tendon (QT) thickness
      value of BD patients was greater than that of FMF patients (P=0.00) or the
      controls' (P=0.01). The mean Achilles tendon (AT) thickness value of BD patients
      was greater than that of controls' (P=0.05) only. There was not any difference
      between the tendon thickness measurements of either group of patients with and
      without arthritic involvement. CONCLUSION: Our first and preliminary findings
      pertaining to increased tendon thicknesses in FMF (TT) and BD (QT and AT)
      patients should be complemented with future histological and clinical studies.
      The functional relevance of tendon thickening, its probable reflection on the
      rupture risk and the role of each disease related contributing factor remain to
      be uncovered.

PMID- 16650793
TI  - Thoracic outlet syndrome portending Klippel-Feil syndrome.

PMID- 16650794
TI  - The genetics of spondyloarthropathies.
AB  - The spondyloarthropathies constitute a group of inflammatory joint diseases
      linked by shared characteristics that include a strong common genetic background.
      Genetic factors include major histocompatibility complex (MHC) genes, among which
      HLA-B27 contributes 30% of the overall genetic susceptibility to
      spondyloarthropathies, and non-MHC genes, none of which have been identified to
      date. Genome screens have identified regions that may contain susceptibility
      genes for spondyloarthropathies. In particular, a locus on the long arm of
      chromosome 9 (9q31-34) was identified by two groups working independently from
      each other. Studies using the candidate gene approach ruled out a role for most
      of the tested genes, including CARD15/NOD2. However, several independent groups
      have reported significant associations between ankylosing spondylitis and the IL
      1 gene cluster on the long arm of chromosome 2.

PMID- 16650795
TI  - [Foetal rhinopharyngeal teratoma: antenatal diagnosis and prognosis. Case
      report].
AB  - Fetal teratomas are commonly found in the sacrococcygeal area. More rarely, these
      tumors may be found in cervicofacial forms. Rhinopharyngeal teratoma represent an
      extremely rare congenital tumor, often resulting in intracranial extension,
      obstruction of the respiratory or the digestive pathways and rapid asphyxia
      following birth. We report a case of rhinopharyngeal teratoma identified in a
      foetus at 18 weeks of gestation. The diagnosis was made by antenatal ultrasound
      and IRM. Tumor invaded the cavum and the right infratemporal region with no
      intracranial extension. The pregnancy was interrupted at 27 weeks of gestation.
      Authors discuss the difficulties to establish antenatal diagnosis by ultrasound,
      and those to decide what treatment to carry out.

PMID- 16650796
TI  - [Endometriosis and infertility].
AB  - Relationship between infertility and endometriosis is still controversial. Many
      mechanisms have been reported such as anatomical disorders, biologic and
      cytological modifications of peritoneal liquid, functional ovarian and
      endometrial disorders, reduced embryo quality. Management of infertility related
      to endometriosis is difficult and no consensus has been published yet. Following
      recent clinical data, therapeutic strategies are discussed.

PMID- 16650797
TI  - Determination of nucleic acids with a near infrared cyanine dye using resonance
      light scattering technique.
AB  - A new method for the determination of nucleic acids has been developed based on
      the enhancement effect of resonance light scattering (RLS) with a cationic near
      infrared (NIR) cyanine dye. Under the optimal conditions, the enhanced RLS
      intensity at 823 nm is proportional to the concentration of nucleic acids in the
      range of 0-400 ng mL-1 for both calf thymus DNA (CT DNA) and fish sperm DNA (FS
      DNA), 0-600 ng mL-1 for snake ovum RNA (SO RNA). The detection limits are 3.5 ng
      mL-1, 3.4 ng mL-1 and 2.9 ng mL-1 for CT DNA, FS DNA and SO RNA, respectively.
      Owing to performing in near infrared region, this method not only has high
      sensitivity endowed by RLS technique but also avoids possible spectral
      interference from background. It has been applied to the determination of nucleic
      acids in synthetic and real samples and satisfactory results were obtained.

PMID- 16650798
TI  - FT-IR, FT-Raman and SERS spectra of pyridine-3-sulfonic acid.
AB  - FT-IR and FT-Raman spectra of pyridine-3-sulfonic acid are recorded and analysed.
      Surface enhanced Raman scattering (SERS) spectrum is recorded in a silver
      colloid. The bands due to upsilonCH, upsilonSO are enhanced in the SERS spectrum.
      A likely 'perpendicular orientation' of the molecule on the silver surface is
      suggested.

PMID- 16650799
TI  - Elevated levels of serum soluble E-selectin in patients with chronic hepatitis B:
      Correlation with T lymphocyte subsets, NK cells and liver inflammation.
AB  - BACKGROUND: It has been reported that serum soluble E-selectin (sE-selectin) may
      be increased in some inflammatory liver diseases. The purpose of our study was to
      investigate changes of sE-selectin, T lymphocyte subsets, natural killer (NK)
      cells, and HBV load in patients with chronic hepatitis B (CHB), analyze the
      relationship between them, and discuss their significances. METHODS: Fifty-four
      patients with chronic hepatitis B and fourteen controls were studied. Serum sE
      selectin, T lymphocyte subsets, NK cells, and hepatitis B virus (HBV) load were
      detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), and
      fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively.
      RESULTS: sE-selectin level in patients with CHB increased significantly than that
      in controls (p<0.01). The percentages of CD4 positive cells and NK cells
      decreased while the percentage of CD8 positive cells increased significantly in
      CHB patients than in controls (p<0.01, respectively). sE-selectin level
      significantly related to levels of T lymphocyte subsets, NK cells, serum alanine
      aminotransferase (sALT) and aspartate aminotransferase (sAST) (p<0.01,
      respectively), but had no relationship with HBV level. CONCLUSION: The sE
      selectin levels in patients with chronic hepatitis B increase significantly and
      correlate to liver inflammation, suggesting that sE-selectin can be considered as
      an additional useful marker of CHB inflammatory activity, and E-selectin may play
      part of role in pathogenesis of chronic hepatitis B.

PMID- 16650800
TI  - Promising pharmacologic innovations in treating pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is the most common form of the interstitial lung
      diseases and is characterized by chronic progressive pulmonary parenchymal
      fibrosis. Although the diagnosis and pathophysiology of this disease have been
      better characterized over the past few years, there remains no effective therapy
      for this disease. Therapies initially aimed at inflammation have proven
      ineffective, and newer strategies targeting aspects of aberrant wound repair
      involving alveolar epithelial cells or septal endothelial cells are now being
      investigated. Therapeutic strategies include the anti-fibrotic agents pirfenidone
      and interferon-gamma. Agents targeting specific cytokines, including connective
      tissue growth factor, transforming growth factor-beta and chemokines, are being
      evaluated. The restoration of oxidant balance and inhibition of leukotrienes
      represent other strategies. Additionally, the role of the
      coagulation/fibrinolytic systems and angiogenesis has also been examined.

PMID- 16650801
TI  - Recent advances in understanding the mechanism of action of bisphosphonates.
AB  - Bisphosphonates (BPs) are widely used in the treatment of diseases associated
      with excessive osteoclast-mediated bone resorption, such as osteoporosis.
      Although several years ago the molecular target of the potent nitrogen-containing
      BPs (N-BPs) was identified as farnesyl diphosphate synthase, an enzyme in the
      mevalonate pathway, recent data have shed new light on the precise mechanism of
      inhibition and demonstrated that the acute-phase reaction, an adverse effect of N
      BPs, is also caused by inhibition of this enzyme. In addition, the identification
      of BP analogues that inhibit different enzymes in the mevalonate pathway could
      lead to the development of novel inhibitors of bone resorption with potential
      applications in the treatment of bone disease.

PMID- 16650802
TI  - The relative merits of anabolics versus anti-resorptive compounds: where our
      targets should be, and whether we are addressing them.
AB  - Currently available results from fracture trials provide evidence that the most
      potent anti-resorptive agents reduce vertebral and non-vertebral fractures
      maximally by 61% and 51%, respectively. Results from the Phase III trial with
      denosumab, the human monoclonal antibody, are eagerly awaited. Denosumab leads to
      sustained 80-90% reduction of bone resorption markers, which is below the level
      commonly achieved with bisphosphonates, and it will be interesting to see whether
      this leads to an improvement in its anti-fracture efficacy over bisphosphonates.
      If the majority of the anti-fracture efficacy of anti-resorptive agents results
      from the reduction of the remodelling space (removal of stress raisers) and the
      conservation of structural integrity of cancellous bone, a further decrease in
      bone resorption might not be desirable, especially as suppression of the residual
      remodelling capacity could lead to an increased risk for accumulation of
      microdamage. In contrast to anti-resorptive agents, the bone anabolic parathyroid
      hormone activates modelling drifts, which act to increase trabecular thickness
      and add bone predominantly on the endocortical, and to a lesser degree the
      periosteal, surface. Despite its anabolic nature, reduction of vertebral and non
      vertebral fractures is only marginally better than those achieved with anti
      resorptive agents. Ageing compromises locomotor capacity and is associated with
      an increased risk of falls. Perhaps it is time to shift our attendance to the age
      related deterioration of muscle or neuromuscular function as a target and add
      this 'adjuvant therapy' to the potent anti-remodelling and bone anabolic agents
      available for the treatment of osteoporosis if we truly want to reduce fracture
      incidence beyond what is possible today.

PMID- 16650803
TI  - Reviving exhausted T lymphocytes during chronic virus infection by B7-H1
      blockade.
AB  - Cytotoxic T lymphocytes (CTLs) are killer cells that are crucial in the control
      of viral pathogens and cancers. They can become exhausted during chronic viral
      infection, a phenomenon that consists of a reduction in both number and
      functionality of CTLs. Recently, Barber and colleagues demonstrated that B7-H1
      (also called PD-L1), a cell-surface molecule that is widely distributed in
      tissues, was necessary for the maintenance of T-cell exhaustion in a chronic
      infection mouse model of lymphocytic choriomeningitis virus (LCMV). PD-1, the
      receptor of B7-H1, was greatly upregulated on CTLs in response to LCMV, and its
      expression was maintained during chronic infection. Blockade of the B7-H1-PD-1
      pathway by a monoclonal antibody restored CTL function and reduced viral burden.
      These results suggest a new strategy for the treatment of chronic viral
      infection.

PMID- 16650804
TI  - Prostaglandins and the colon cancer connection.
AB  - Colorectal cancer is a leading cause of cancer-related deaths throughout the
      world. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the few agents
      that are known to inhibit colorectal tumorigenesis. The mechanisms that underlie
      this effect are poorly understood. Two recent studies have provided some
      significant insight. Castellone and colleagues showed that prostaglandin E2
      modulates the beta-catenin signaling axis, a key pathway for colorectal
      tumorigenesis. Holla and colleagues showed that prostaglandin E2 might act via a
      nuclear receptor. These findings shed light on the mechanisms that underlie
      prostaglandin action, and provide a molecular framework for developing future
      treatments for colorectal cancer.

PMID- 16650805
TI  - The role of apoptosis in neuromuscular diseases and prospects for anti-apoptosis
      therapy.
AB  - Although genetic mutations that are responsible for most of the inherited
      neuromuscular diseases have been identified, the molecular and cellular
      mechanisms that cause muscle and nerve depletion are not well understood and
      therapies are lacking. Histological studies of many neuromuscular diseases
      indicated that loss of motor-nerve and/or skeletal-muscle function might be due
      to excessive cell death by apoptosis. Recent studies have confirmed this
      possibility by showing that pathology in mouse models of amyotrophic lateral
      sclerosis, congenital muscular dystrophy, oculopharyngeal muscular dystrophy and
      collagen-VI deficiency, but not Duchenne muscular dystrophy, is significantly
      ameliorated by genetic or pharmacological interventions that have been designed
      to inhibit apoptosis. Thus, apoptosis greatly contributes to pathology in mouse
      models of several neuromuscular diseases, and appropriate anti-apoptosis therapy
      might therefore be beneficial for the corresponding human diseases.

PMID- 16650806
TI  - A statistical method for estimating the proportion of differentially expressed
      genes.
AB  - Microarrays have been widely used to identify differentially expressed genes. One
      related problem is to estimate the proportion of differentially expressed genes.
      For some complex diseases, the amount of differentially expressed genes may be
      relatively small and these genes may only have subtly differential expressions.
      For these microarray data, it is generally difficult to efficiently estimate the
      proportion of differentially expressed genes. In this study, I propose a
      likelihood-based method coupled with an expectation-maximization (E-M) algorithm
      for estimating the proportion of differentially expressed genes. The proposed
      method has favorable performances if either (i) the P values of differentially
      expressed genes are homogeneously distributed or (ii) the proportion of
      differentially expressed genes is relatively small. In both of these situations,
      I showed through simulations that the proposed method gave satisfactory
      performances when it was compared to other existing methods. As applications,
      these methods were applied to two microarray gene expression data sets generated
      from different platforms.

PMID- 16650807
TI  - The "perivascular pump" driven by arterial pulsation is a powerful mechanism for
      the distribution of therapeutic molecules within the brain.
AB  - We investigated the movement of interstitially infused macromolecules within the
      central nervous system (CNS) in rats with high and low blood pressure (BP)/heart
      rate and in rats euthanized immediately before infusion (no heart action). Adeno
      associated virus 2 (AAV2), fluorescent liposomes, or bovine serum albumin was
      infused into rat striatum (six hemispheres per group) by convection-enhanced
      delivery (CED). After infusion, distribution volumes were evaluated. The rats
      with high BP/heart rate displayed a significantly larger distribution of the
      infused molecules within the injected site and more extensive transport of those
      molecules to the globus pallidus. This difference was particularly apparent for
      AAV2, for which a 16.5-fold greater distribution of viral capsids was observed in
      the rats with high BP/heart rate than in the rats with no heartbeat. Similar
      results were observed for liposomes, despite their larger diameter. The
      distribution of all infused molecules in all rats that had low or no blood flow
      was confined to the space around brain blood vessels. These findings show that
      fluid circulation within the CNS through the perivascular space is the primary
      mechanism by which viral particles and other therapeutic agents administered by
      CED are spread within the brain and that cardiac contractions power this process.

PMID- 16650808
TI  - Gene transfer approaches for gynecological diseases.
AB  - Gene transfer presents a potentially useful approach for the treatment of
      diseases refractory to conventional therapies. Various preclinical and clinical
      strategies have been explored for treatment of gynecological diseases. Given the
      direst need for novel treatments, much of the work has been performed with
      gynecological cancers and ovarian cancer in particular. Although the safety of
      many approaches has been demonstrated in early phase clinical trials, efficacy
      has been mostly limited so far. Major challenges include improving gene transfer
      vectors for enhanced and selective delivery and achieving effective penetration
      and spread within advanced and complex tumor masses. This review will focus on
      current and developmental gene transfer applications for gynecological diseases.

PMID- 16650809
TI  - An interdepartmental Ph.D. program in computational biology and bioinformatics:
      the Yale perspective.
AB  - Computational biology and bioinformatics (CBB), the terms often used
      interchangeably, represent a rapidly evolving biological discipline. With the
      clear potential for discovery and innovation, and the need to deal with the
      deluge of biological data, many academic institutions are committing significant
      resources to develop CBB research and training programs. Yale formally
      established an interdepartmental Ph.D. program in CBB in May 2003. This paper
      describes Yale's program, discussing the scope of the field, the program's goals
      and curriculum, as well as a number of issues that arose in implementing the
      program. (Further updated information is available from the program's website,
      www.cbb.yale.edu.)

PMID- 16650810
TI  - Histone H2A phosphorylation and H3 methylation are required for a novel Rad9 DSB
      repair function following checkpoint activation.
AB  - In budding yeast, the Rad9 protein is an important player in the maintenance of
      genomic integrity and has a well-characterised role in DNA damage checkpoint
      activation. Recently, roles for different post-translational histone
      modifications in the DNA damage response, including H2A serine 129
      phosphorylation and H3 lysine 79 methylation, have also been demonstrated. Here,
      we show that Rad9 recruitment to foci and bulk chromatin occurs specifically
      after ionising radiation treatment in G2 cells. This stable recruitment
      correlates with late stages of double strand break (DSB) repair and,
      surprisingly, it is the hypophosphorylated form of Rad9 that is retained on
      chromatin rather than the hyperphosphorylated, checkpoint-associated, form.
      Stable Rad9 accumulation in foci requires the Mec1 kinase and two independently
      regulated histone modifications, H2A phosphorylation and Dot1-dependent H3
      methylation. In addition, Rad9 is selectively recruited to a subset of Rad52
      repair foci. These results, together with the observation that rad9Delta cells
      are defective in repair of IR breaks in G2, strongly indicate a novel post
      checkpoint activation role for Rad9 in promoting efficient repair of DNA DSBs by
      homologous recombination.

PMID- 16650811
TI  - Less common applications of monoliths: preconcentration and solid-phase
      extraction.
AB  - Monolithic materials are finding their place in a variety of fields. While liquid
      chromatography is the most emphasized use of this new category of porous media,
      some other just as important applications are eclipsed by the success of
      monolithic columns. This review article describes all current facets of use of
      monoliths in preconcentration and solid-phase extraction. In addition to the
      typical off line use that does not seem to be the main stream application for the
      monolithic materials, in-line connection of the preconcentration with HPLC,
      electrochromatography, electrophoresis, enzymatic digestion, as well as its
      applications in microfluidics are presented.

PMID- 16650812
TI  - Substrate specificity of Aspergillus oryzae family 3 beta-glucosidase.
AB  - Among glycoside hydrolases, beta-glucosidase plays a unique role in many
      physiological and biocatalytical processes that involve the beta-linked O
      glycosyl bond of various oligomeric saccharides or glycosides. Structurally, the
      enzyme can be grouped into glycoside hydrolase family 1 and 3. Although the basic
      ("retaining, double-displacement") mechanism for the catalysis of family 3 beta
      glucosidase has been established, in-depth understanding of its structure
      function relationship, particularly the substrate specificity that is of great
      interest for developing the enzyme as a versatile biocatalyst, remains limited.
      To further probe the active site, we carried out a comparative study on a family
      3 beta-glucosidase from Aspergillus oryzae with substrates and competitive
      inhibitors of different structures, in attempt to evaluate the site-specific
      spatial and chemical interactions between a pyranosyl substrate and the enzyme.
      Our results showed the enzyme having a strict stereochemical requirement (to
      accommodate beta-d-glucopyranose) for its "-1" active subsite, in contrast to its
      family 1 counterpart.

PMID- 16650813
TI  - IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK
      pathway.
AB  - IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent
      report suggested that IL-18 plays a key role in regulating the immune escape of
      melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit
      angiogenesis in several cancers but some studies have reported that it stimulates
      angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related
      to tumor proliferation and metastasis. This study investigated the relationship
      between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the
      cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1
      protein production by IL-18 increased in both a dose- and time-dependent manner.
      The cells were next treated with specific inhibitors in order to determine the
      signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1
      expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific
      inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of
      phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in
      TSP-1 expression involving JNK.

PMID- 16650814
TI  - Replication-associated strand asymmetries in vertebrate genomes and implications
      for replicon size, DNA replication origin, and termination.
AB  - Strand compositional asymmetry has been observed in prokaryotes and used in
      predicting prokaryotic DNA replication origins and termini. However, it was not
      found in eukaryotic genomes by the same methods. We propose that transcription
      associated strand asymmetries mask the replication-associated ones. By analyzing
      the nucleotide composition of intergenic sequences larger than 50 kb by
      cumulative skew diagrams (CSD), we found replication-associated strand asymmetry
      in vertebrate genomes. Furthermore, we found that the most common replicon sizes
      in vertebrates are 50-100 kb, and show evidence that the replication origin and
      termination regions of vertebrate genomes range from a discrete site to a broad
      zone.

PMID- 16650815
TI  - DNA binding-independent transcriptional activation of the vascular endothelial
      growth factor gene (VEGF) by the Myb oncoprotein.
AB  - Myb is a key transcription factor that can regulate proliferation,
      differentiation, and apoptosis, predominantly in the haemopoietic system.
      Abnormal expression of Myb is associated with a number of cancers, both
      haemopoietic and non-haemopoietic. In order to better understand the role of Myb
      in normal and tumorigenic processes, we undertook a cDNA array screen to identify
      genes that are regulated by this factor. In this way, we identified the gene
      encoding vascular endothelial growth factor (VEGF) as being potentially regulated
      by the Myb oncoprotein in myeloid cells. To determine whether this was a direct
      effect on VEGF gene transcription, we examined the activity of the murine VEGF
      promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was
      found that WT Myb was able to activate the VEGF promoter and that a minimal
      promoter region of 120 bp was sufficient to confer Myb responsiveness.
      Surprisingly, activation of the VEGF promoter was independent of DNA binding by
      Myb. This was shown by the use of DNA binding-defective Myb mutants and by
      mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of
      Sp1 sites within this region abolished Myb-mediated regulation of a reporter
      construct, suggesting that Myb DNA binding-independent activation of VEGF
      expression occurs via these Sp1 binding elements. Regulation of VEGF production
      by Myb has implications for the potential role of Myb in myeloid leukaemias and
      in solid tumours where VEGF may be functioning as an autocrine growth factor.

PMID- 16650816
TI  - Maternally inherited non-syndromic hearing loss associated with mitochondrial 12S
      rRNA A827G mutation in a Chinese family.
AB  - We explored the clinical and molecular characterization of a Chinese family with
      non-syndromic hearing impairment. Clinical evaluations revealed a possible
      maternal inheritance pattern, and showed an extremely similar phenotype of
      hearing loss including the age of onset, severity, and audiometric configuration.
      Sequence analysis of the mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes led to
      the identification of a homoplasmic A827G mutation in all maternal relatives,
      which was absent in other family members and 40 Chinese controls. This mutation
      has previously been reported sporadically in a few individuals with
      aminoglycoside-induced and non-syndromic hearing loss. The A827G mutation is
      located at the A-site of the mitochondrial 12S rRNA gene which is highly
      evolutionarily conserved in mammals. The occurrence of the A827G mutation in
      these genetically unrelated subjects strongly suggests that this mutation is
      involved in the pathogenesis of hearing impairment. However, incomplete
      penetrance of hearing loss indicates that the A827G mutation alone is not
      sufficient to produce clinical phenotype but requires the involvement of modifier
      factors for the phenotypic expression, even though aminoglycosides and GJB2 gene
      may not contribute to the penetrance of the A827G mutation in this Chinese
      family. In contrast with the variable phenotype of hearing loss associated with
      other mitochondrial mutations, all of the patients in our family exhibited
      strikingly similar clinical features. This discrepancy likely reflects the
      difference of genetic backgrounds between this pedigree and others.

PMID- 16650817
TI  - Protease-activated receptor-2 regulates vascular endothelial growth factor
      expression in MDA-MB-231 cells via MAPK pathways.
AB  - Protease-activated receptor 2 (PAR2) is a G-protein coupled receptor that is
      cleaved and activated by serine proteases including the coagulation protease
      factor VIIa (FVIIa). There is evidence that PAR2 function contributes to
      angiogenesis, but the mechanisms involved are poorly defined. Here we show that
      PAR2 activation in human breast cancer cells leads to the upregulation of
      vascular endothelial growth factor (VEGF). Activation of PAR2 with agonist
      peptide (AP), trypsin or FVIIa results in a robust increase of VEGF message and
      protein. Incubation of cells with PAR1-AP, PAR3-AP, PAR4-AP, or thrombin has only
      a modest effect on VEGF production. Cleavage blocking antibodies show that FVIIa
      mediated VEGF production is PAR2 mediated. Mitogen-activated protein kinase
      (MAPK) pathway inhibitors U0126 and SB203580 inhibit PAR2-mediated VEGF
      production. Incubation of cells with PAR2-AP leads to significant extracellular
      regulated kinase1/2 (ERK1/2) and p38 MAPK phosphorylation and activation.
      Collectively, these data suggest that PAR2 signaling through MAPK pathways leads
      to the production of proangiogenic VEGF in breast cancer cells.

PMID- 16650818
TI  - Oligomeric forms of peptide fragment PrP(214-226) in solution are preferentially
      recognized by PrP(Sc)-specific antibody.
AB  - A specific monoclonal antibody (mAb) V5B2 that discriminates between brain tissue
      of Creutzfeldt-Jakob disease patients and that from normal controls without
      proteinase K digestion has been prepared using a 13-residue synthetic peptide P1
      from the primary structure of human PrP. In the light of the specific interaction
      between mAb V5B2 and the pathological isoform of PrP (PrP(Sc)), we investigated
      the solution behavior of antigen P1 and its interactions with mAb V5B2. Our
      results show that V5B2 recognizes epitope P1 in dimeric/oligomeric forms in
      solution and in the fibril-like aggregates, as well as in PrP(Sc) aggregates, and
      demonstrate that the specific epitope is present in all of these forms, but not
      in PrP(C).

PMID- 16650819
TI  - Cellular disulfide-reducing capacity: an integrated measure of cell redox
      capacity.
AB  - To assess the disulfide reduction capacity of intact cells, EA.hy926 endothelial
      cells were incubated with alpha-lipoic acid in the presence of 5,5'-dithiobis(2
      nitrobenzoic acid) (DTNB). Alpha-lipoic acid was reduced within cells to
      dihydrolipoic acid, which could be quantified upon efflux from the cells as
      reduction of DTNB. Uptake of both alpha-lipoic acid and alpha-lipoamide occurred
      at least in part via a medium chain fatty acid transporter, based on inhibition
      by octanoate. Alpha-lipoic acid was reduced within cells by pyridine nucleotide
      disulfide oxidoreductases, since it is not reduced by GSH and since its reduction
      was inhibited by carmustine. Nonetheless, reduction was also dependent on the
      cellular redox environment, since it was inhibited by the redox cycling of
      menadione, by decreasing intracellular GSH, and by reduction of dehydroascorbate.
      Together, these results show that alpha-lipoic acid-dependent DTNB reduction
      provides a simple method to assess the disulfide-reducing capacity of intact
      cells, especially as determined by pyridine nucleotide-disulfide oxidoreductases.

PMID- 16650820
TI  - The expression of inhibin beta B is high in human adipocytes, reduced by weight
      loss, and correlates to factors implicated in metabolic disease.
AB  - Adipose tissue is an endocrine organ that produces and secretes adipokines. The
      aim of this study was to identify genes predominantly expressed in human
      subcutaneous adipocytes. For this purpose, an algorithm was developed and DNA
      microarray expression profiles from 33 human tissues and cell types were used to
      select genes. Inhibin beta B (INHBB; coding for the activin betaB subunit) was
      identified and high expression in adipocytes was confirmed by real-time PCR and
      immunohistochemistry. INHBB expression in adipose tissue was down regulated by
      diet-induced weight loss (p<0.001). Furthermore, INHBB expression was positively
      correlated to total (p<0.001) and subcutaneous (p<0.01) adipose tissue areas and
      serum levels of fasting insulin (p<0.01) and cholesterol (p<0.05). In conclusion,
      INHBB expression was high in human adipocytes, reduced by weight loss and adipose
      tissue INHBB mRNA levels correlated to metabolic risk factors. This suggests that
      activin B produced in adipocytes may play a role in the metabolic syndrome.

PMID- 16650821
TI  - Mg2+ mimicry in the promotion of group I ribozyme activities by aminoglycoside
      antibiotics.
AB  - Aminoglycoside antibiotics inhibit several types of ribozymes, including group I
      introns, by displacing critical Mg2+ ions. However, they stimulate activity of
      the small hairpin ribozyme. We show here that aminoglycosides promote self
      splicing of the Cr.psbA2 group I intron at subthreshold Mg2+ concentrations.
      Neomycin is the most effective of the aminoglycosides tested; it stimulates
      splicing of Cr.psbA2 at micromolar concentrations, and, in this respect, is >100
      fold more effective than spermidine. At optimal Mg2+ for Cr.psbA2 splicing, these
      drugs, especially kanamycin B and tobramycin, promote GTP attack at the 3' splice
      site. Kinetic analysis suggests that this is due to an alternatively folded state
      of the ribozyme that is induced, or stabilized, by aminoglycosides. A similar
      effect is observed at high Mg2+ concentrations. Comparing the effects of
      structurally related aminoglycosides indicates that splicing promotion is more
      sensitive to drug structure than misfolding and occurs at lower drug
      concentrations. These data show that aminoglycosides can promote biochemical
      activities of a large ribozyme by acting as a Mg2+ mimic. The results also
      underscore the functional diversity of group I introns in nature.

PMID- 16650822
TI  - Functional insights from the molecular modelling of a novel two-component system.
AB  - Two-component systems (TCSs) are the major signalling pathway in bacteria and
      represent potential drug targets. Among the 11 paired TCS proteins present in
      Mycobacterium tuberculosis H37Rv, the histidine kinases (HKs) Rv0600c (HK1) and
      Rv0601c (HK2) are annotated to phosphorylate one response regulator (RR) Rv0602c
      (TcrA). We wanted to establish the sequence-structure-function relationship to
      elucidate the mechanism of phosphotransfer using in silico methods. Sequence
      alignments and codon usage analysis showed that the two domains encoded by a
      single gene in homologous HKs have been separated into individual open-reading
      frames in M. tuberculosis. This is the first example where two incomplete HKs are
      involved in phosphorylating a single RR. The model shows that HK2 is a unique
      histidine phosphotransfer (HPt)-mono-domain protein, not found as lone protein in
      other bacteria. The secondary structure of HKs was confirmed using "far-UV"
      circular dichroism study of purified proteins. We propose that HK1 phosphorylates
      HK2 at the conserved H131 and the phosphoryl group is then transferred to D73 of
      TcrA.

PMID- 16650823
TI  - Delta-sarcoglycan is necessary for early heart and muscle development in
      zebrafish.
AB  - Delta-sarcoglycan, one member of the sarcoglycan complex, is a very conservative
      muscle-specific protein exclusively expressed in the skeletal and cardiac muscles
      of vertebrates. Mutations in sarcoglycans are known to be involved in limb-girdle
      muscular dystrophy (LGMD) and dilated cardiomyopathy (DCM) in humans. To address
      the role of delta-sarcoglycan gene in zebrafish development, we have studied
      expression pattern of delta-sarcoglycan in zebrafish embryos and examined the
      role of delta-sarcoglycan in zebrafish embryonic development by morpholino.
      Strong expression of delta-sarcoglycan was observed in various muscles including
      those of the segment, heart, eye, jaw, pectoral fin, branchial arches, and swim
      bladder in zebrafish embryo. Delta-sarcoglycan was also expressed in midbrain and
      retina. Knockdown of delta-sarcoglycan resulted in severe abnormality in both the
      cardiac and skeletal muscles. Some severe ones displayed serious morphological
      abnormality such as hypoplastic head, linear heart, very weak heartbeats, and
      runtish trunk, all dead within 5 dpf. Whole-mount in situ hybridization analysis
      showed that adaxial cells and muscle pioneers were affected in delta-sarcoglycan
      knockdown embryos. In addition, absence of delta-sarcoglycan protein severely
      delayed the cardiac development and influenced the differentiation of cardiac
      muscle, and the cardiac left-right asymmetry was dramatically changed in
      morpholino-treated embryos. These data together suggest that delta-sarcoglycan
      plays an important role in early heart and muscle development.

PMID- 16650824
TI  - Lysophosphatidylcholine (LPC) attenuates macrophage-mediated oxidation of LDL.
AB  - We have previously shown that paraoxonase 1 action on macrophages produced
      lysophosphatidylcholine (LPC) and significantly decreased cell-mediated LDL
      oxidation. Thus, in the present study, we questioned whether LPC can directly
      inhibit macrophage-mediated oxidation of LDL. Addition of increasing LPC
      concentrations (0-5 microM) to J774A.1 macrophages, mouse peritoneal macrophages
      (MPM), or to human monocytes-derived macrophages (HMDM) resulted in up to 83%,
      67%, and 75% inhibition in cell-mediated oxidation of LDL, respectively. The
      mechanism for this LPC effect involves up to 60% inhibition of superoxide anion
      release from MPM in response to phorbol ester (PMA), 26% inhibition of PMA
      induced NADPH oxidase activation (p47phox translocation from the cytosol to the
      plasma membrane), and a 2-fold stimulation of the macrophage paraoxonase 2 (PON2)
      lactonase activity. We thus conclude that inhibition of macrophage-mediated
      oxidation of LDL by LPC can contribute to attenuation of macrophage foam cell
      formation and atherosclerotic lesion development.

PMID- 16650825
TI  - Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor
      cells.
AB  - Interferon-alpha (IFN-alpha) is used for biotherapy of neuroendocrine carcinomas.
      The interferon-lambdas (IL-28A/B and IL-29) are a novel group of interferons. In
      this study, we investigated the effects of the IFN-lambdas IL-28A and IL-29 on
      human neuroendocrine BON1 tumor cells. Similar to IFN-alpha, incubation of BON1
      cells with IL-28A (10 ng/ml) and IL-29 (10 ng/ml) induced phosphorylation of
      STAT1, STAT2, and STAT3, significantly decreased cell numbers in a proliferation
      assay, and induced apoptosis as demonstrated by poly(ADP-ribose) polymerase
      (PARP)-cleavage, caspase-3-cleavage, and DNA-fragmentation. Stable overexpression
      of suppressor of cytokine signaling proteins (SOCS1 and SOCS3) completely
      abolished the aforementioned effects indicating that SOCS proteins act as
      negative regulators of IFN-lambda signaling in BON1 cells. In conclusion, the
      novel IFN-lambdas IL-28A and IL-29 potently induce STAT signaling and
      antiproliferative effects in neuroendocrine BON1 tumor cells. Thus, IFN-lambdas
      may hint a promising new approach in the antiproliferative therapy of
      neuroendocrine tumors.

PMID- 16650826
TI  - Elemental analysis of the Mycobacterium avium phagosome in Balb/c mouse
      macrophages.
AB  - Using a hard X-ray microprobe, we showed recently that in unstimulated peritoneal
      macrophages from C57BL/6 mice, the phagosome of pathogenic mycobacteria
      (Mycobacterium tuberculosis and Mycobacterium avium) can accumulate iron. We
      expanded our studies to the M. avium infection of peritoneal macrophages of
      Balb/c mice that show a similar degree of M. tuberculosis and M. avium-related
      chronic disease, but a higher susceptibility towards other intracellular
      pathogens such as Listeria monocytogenes, Leishmania major, or Brucella abortus
      as compared to C57BL/6 mice. Similar to C57BL/6 macrophages, the iron
      concentration in Balb/c macrophages increased significantly after 24 h of
      infection. A significant increase of the chlorine and potassium concentrations
      was observed in the Balb/c phagosomes between 1 and 24 h, in contrast with
      macrophages from C57BL/6 mice. The absolute elemental concentrations of calcium
      and zinc were higher in the mycobacterial phagosomes of Balb/c mice. We
      hypothesize that a potassium channel is abundant in the phagosome in macrophages
      that may be related to microbiocidal killing, similar to the requirement of
      potassium channels for microbiocidal function in neutrophils.

PMID- 16650827
TI  - STAT5 activators modulate acyl CoA oxidase (AOX) expression in adipocytes and
      STAT5A binds to the AOX promoter in vitro.
AB  - Growth hormone (GH) diminishes adipose tissue mass in vivo and prolactin (PRL)
      can also modulate adipocyte metabolism. Both GH and PRL are potent activators of
      STAT5 and exert a variety of effects on adipocyte gene expression. In this study,
      we have demonstrated that GH and PRL increase the mRNA of acyl CoA oxidase in 3T3
      L1 adipocytes. We also identified seven putative STAT elements in the murine AOX
      promoter. We observed that GH modulates protein binding to the majority of these
      promoter elements. However, GH induced very potent binding to -1841 to -1825 of
      the murine AOX promoter. EMSA supershift analysis revealed that this site was
      specifically bound by STAT5A, but not by STAT1 or STAT3. Taken together, these
      data strongly suggest that GH directly induces the expression of AOX in
      adipocytes through STAT5A binding to the -1841 to -1825 site within the AOX
      promoter. Our observations are consistent with other studies that demonstrate
      that STAT5 activators modulate fatty acid oxidation.

PMID- 16650828
TI  - The proteasome activator PA28 functions in collaboration with Hsp90 in vivo.
AB  - We have previously shown that the proteasome activator PA28 is essential to Hsp90
      dependent protein refolding in vitro, where PA28 mediates transfer of the Hsp90
      bound substrate protein to the Hsc70/Hsp40 chaperone machine for its correct
      refolding. This observation suggests that PA28 may also collaborate with Hsp90 in
      cells. To examine this possibility, here we have used double-stranded RNA
      interference (RNAi) against PA28 in Caenorhabditis elegans mutants of daf-21,
      which encodes Hsp90. We show that C. elegans PA28 facilitates Hsp90-initiated
      protein refolding, albeit with an activity lower than that of mouse PA28
      proteins. RNAi-mediated knockdown of PA28 significantly suppresses the Daf-c
      (dauer formation constitutive) phenotype of the daf-21 mutant, but it has no
      affect on the distinct defects of this mutant in sensing odorants. Taking these
      results together, we conclude that PA28 is likely to function in collaboration
      with Hsp90 in vivo.

PMID- 16650829
TI  - The presence of ABCG2-dependent side population cells in human periodontal
      ligaments.
AB  - Periodontal ligament (PDL) is capable of regenerating several types of
      periodontal tissues. However, the stem cells in PDL have been less well
      characterized. Recently, it has been represented that stem cells have a potent
      ability to exclude Hoechst dye, and cells possessing this phenotype are termed
      "side population (SP)." In addition, it is suggested that the SP cells are
      ubiquitously present in adult tissues, therefore, we investigated the presence of
      SP cells in PDL. Hoechst dye efflux assay showed that PDL cells include 3.9% SP
      cells. This SP profile disappeared in the presence of verapamil or reserpine.
      Only ABCG2-expressing cells were detected in PDL cells by flow cytometric
      analysis. Furthermore, RT-PCR demonstrated that ABCG2 mRNA expression remarkably
      correlated with PDL SP phenotype. Our findings demonstrate that PDL contains
      ABCG2-dependent SP cells. Hence, it is possible that this population could
      contribute to periodontal tissue regeneration as PDL stem cells.

PMID- 16650830
TI  - Effect of chronic administration of duloxetine on serotonin and norepinephrine
      transporter binding sites in rat brain.
AB  - BACKGROUND: Chronic treatment of rats with certain selective serotonin or
      norepinephrine reuptake inhibitors produces significant decreases, respectively,
      in serotonin and norepinephrine transporter binding sites in brain. Duloxetine
      may be a dual serotonin/norepinephrine reuptake inhibitor, as it is only a
      slightly more potent inhibitor of serotonin than norepinephrine uptake in vitro.
      Consequently, we hypothesized that chronic duloxetine treatment, at doses
      producing serum levels within its therapeutic range, would affect both monoamine
      transporters dose-dependently, with a higher dose causing greater reductions of
      binding sites for both transporters. METHODS: Rats were treated with either 4 or
      8 mg/kg/d of duloxetine, paroxetine, desipramine, or vehicle via subcutaneous
      osmotic minipumps for 21 days. Binding sites for serotonin and norepinephrine
      transporters were measured in amygdala and hippocampus using quantitative
      autoradiography. RESULTS: Both doses of duloxetine and paroxetine produced
      equivalent and significant decreases in [3H] cyanoimipramine binding to serotonin
      transporters, but only desipramine treatment significantly reduced [3H]
      nisoxetine binding to norepinephrine transporters. CONCLUSIONS: At doses
      producing rat serum concentrations in the range achieved in patients at
      recommended daily doses of the drug, duloxetine behaves in vivo more as a
      selective serotonin reuptake inhibitor than a dual reuptake inhibitor in its
      capacity to selectively reduce serotonin transporter density.

PMID- 16650831
TI  - Ketamine dose-dependently induces high-frequency oscillations in the nucleus
      accumbens in freely moving rats.
AB  - BACKGROUND: In humans, subanesthetic doses of ketamine and recovery from ketamine
      anesthesia are associated with psychotic-like behavior. In rodents, ketamine
      produces hyperactivity, stereotypies, and abnormal social interaction used to
      model certain features of schizophrenia. Increasing evidence has implicated
      aberrant activity in the nucleus accumbens (NAc) with the pathophysiology of
      schizophrenia. METHODS: Here, we examined the effect of an IP injection of
      ketamine (10, 25, 50, and 200 mg/kg) and d-amphetamine (3 mg/kg) on local field
      potentials in the rodent NAc. Locomotor activity was recorded simultaneously.
      RESULTS: Spontaneous high-frequency oscillations (HFO) (140-180 Hz) were present
      in local field potentials recorded from the NAc. Ketamine dose-dependently
      induced rapid and substantial increases in HFO that correlated with behavioral
      hyperactivity. Similarly, large increases in HFO occurred during recovery from
      ketamine anesthesia. In contrast, d-amphetamine, which induced locomotor
      activity, produced only small increases in HFO. CONCLUSIONS: We propose that
      ketamine-induced abnormal increases in HFO form part of the complex neurological
      changes in this model of schizophrenia. Ketamine-induced increases in HFO,
      although sharing similar temporal dynamics to hyperactivity, may not be
      functionally related to increased movement.

PMID- 16650832
TI  - Latent class analysis shows strong heritability of the child behavior checklist
      juvenile bipolar phenotype.
AB  - BACKGROUND: The Child Behavior Checklist (CBCL) has been used to provide a
      quantitative description of childhood bipolar disorder (BPAD). Many have reported
      that children in the clinical range on the Attention Problems (AP), Aggressive
      Behavior (AGG), and Anxious-Depressed (A/D) syndromes simultaneously are more
      likely to meet the criteria for childhood BPAD. The purpose of this study was to
      determine if Latent Class Analysis (LCA) could identify heritable phenotypes
      representing the CBCL-Juvenile Bipolar (CBCL-JBD) profile and whether this
      phenotype demonstrates increased frequency of suicidal endorsement. METHODS: The
      CBCL data were received by survey of mothers of twins in two large twin samples,
      the Netherlands Twin Registry. The setting for the study was the general
      community twin sample. Participants included 6246 10-year-old Dutch twins from
      the Netherlands Twin Registry. The main outcome measure consisted of the LCA on
      the items comprising the AP, AGG, and A/D subscales and means from the suicidal
      items #18 and #91 within classes. RESULTS: A 7 class model fit best for girls and
      an 8 class fit best for boys. The most common class for boys or girls was one
      with no symptoms. The CBCL-JBD phenotype was the least common--about 4%-5% of the
      boys and girls. This class was the only one that had significant elevations on
      the suicidal items of the CBCL. Gender differences were present across latent
      classes with girls showing no aggression without the CBCL-JBD phenotype and
      rarely showing attention problems in isolation. Evidence of high heritability of
      these latent classes was found with odds ratios. CONCLUSIONS: In a general
      population sample, LCA identifies a CBCL-JBD phenotype latent class that is
      associated with high rates of suicidality, is highly heritable, and speaks to the
      comorbidity between attention problems, aggressive behavior, and
      anxious/depression in children.

PMID- 16650833
TI  - Maturation of executive function in autism.
AB  - BACKGROUND: Executive dysfunction has been reported at different ages in autism.
      It is not clear however, when this impairment emerges or how its expression is
      affected by development. METHODS: 61 non-mentally retarded autism participants
      (AUT) and 61 age, gender, and IQ matched typically developing participants (CON)
      were assessed with two oculomotor executive function tasks, the oculomotor
      delayed response task (ODR) and the antisaccade task (AS), as well as a visually
      guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated
      impairments in response inhibition and spatial working memory at all ages tested.
      Developmental improvements in speed of sensorimotor processing and voluntary
      response inhibition were similar in both groups indicating sparing of some
      attentional control of behavior. Developmental progression in the speed of
      initiating a cognitive plan and maintaining information on line over time,
      however, was impaired in the AUT group indicating abnormal development of working
      memory. CONCLUSIONS: These results indicate that while executive dysfunction is
      present throughout development, there is evidence for both typical and atypical
      developmental progression of executive functions in autism. The plasticity
      suggested by the developmental improvements may have implications regarding
      appropriate developmental epochs and types of interventions aimed at enhancing
      cognitive capacities in individuals with autism.

PMID- 16650834
TI  - Regulation of GDNF and its receptor components GFR-alpha1, -alpha2 and Ret during
      development and in the mature retino-collicular pathway.
AB  - The development of the retino-tectal projection as part of the central visual
      pathway is accomplished around postnatal day (P) 10-14 in rodents, and trophic
      factors are important for topographic refinement of this projection. Emerging
      data indicate that GDNF may influence synaptic plasticity of this projection. To
      date, maturation-dependent kinetics of GDNF release and expression and biological
      function of single GDNF receptors along the retino-collicular pathway are ill
      defined. Here, we examined mRNA and protein expression of GDNF and its
      multicomponent receptor complex in the retina and superior colliculus (SC) during
      postnatal development of the rat visual system, and after optic nerve (ON) injury
      by RT-PCR, immunoblotting and immunofluorescence. Stable mRNA transcription of
      GDNF and its receptors GFR-alpha1, -alpha2 and Ret was found in retina and SC
      throughout development into adulthood and after ON transection. Expression of
      GDNF protein increased during retinal development, declined in adulthood and was
      further reduced in injured retina. In the SC, GDNF peaked at P0, continuously
      declined with maturation, and was undetectable in the deafferentiated SC. GFR
      alpha1 was abundant in retina and SC throughout, while GFR-alpha2 was not
      expressed. Since Ret was localized primarily to the vascular compartment, the
      receptor tyrosine kinase may play a minor role in neuronal GDNF signaling. In
      summary, we provide evidence for GDNF as survival and guidance factor during
      development of the retino-tectal projection with differential regulation in early
      and premature retina and SC. Postlesionally, midbrain targets do not induce GDNF,
      suggesting that retrograde GDNF is not essential for rescue of adult injured
      retinal ganglion cells (RGCs).

PMID- 16650835
TI  - Cell cycle progression is required for nuclear migration of neural progenitor
      cells.
AB  - In the developing brain, neural progenitor cells in the ventricular zone (VZ)
      show a typical migration pattern-interkinetic nuclear migration, in which nuclear
      position within the VZ is correlated with the cell cycle. However, the mechanisms
      underlying this regulation remain unclear. To clarify whether the cell cycle
      progression controls nuclear migration of neural progenitor cells, we determined
      whether chemically induced cell cycle arrest affected nuclear migration patterns
      in the VZ. Administration of 5-azacytidine (5AzC) or cyclophosphamide (CP) to
      pregnant mice induced cell cycle arrest in the fetal neural progenitor cells of
      the telencephalon: 5AzC induced G2/M-phase arrest, and CP induced S-phase arrest.
      We used 5-bromo-2'-deoxyuridine (BrdU) labeling to determine the position of the
      cell in the cell cycle and the nuclei within the VZ at the same time. Cells
      arrested in G2/M-phase stopped migrating in the inner area of the VZ. Cells
      arrested in S-phase stopped migrating in the outer area. These results indicate
      that nuclear position within the VZ was correlated with cell cycle phase, even
      when the cell cycle was disrupted, and that the nuclei of neural progenitor cells
      can migrate only when their cell cycle is going. Our results suggest that cell
      cycle regulators might control the machinery of migration through a common
      regulatory mechanism.

PMID- 16650836
TI  - Individual differences in the functional neuroanatomy of inhibitory control.
AB  - We combined the data of five event-related fMRI studies of response inhibition.
      The re-analysis (n = 71) revealed response inhibition to be accomplished by a
      largely right hemisphere network of prefrontal, parietal, subcortical and midline
      regions, with converging evidence pointing to the particular importance of the
      right frontal operculum. Functional differences were observed between the sexes
      with greater activity in females in many of these cortical regions. Despite the
      relatively narrow age range (18-46), cortical activity, on the whole, tended to
      increase with age, echoing a pattern of functional recruitment often observed in
      the elderly. More absent minded subjects showed greater activity in fronto
      parietal areas, while speed of Go trial responses produced a varied pattern of
      activation differences in more posterior and subcortical areas. Although response
      inhibition produces robust activation in a discrete network of brain regions,
      these results reveal that individual differences impact on the relative
      contribution made by the nodes of this network.

PMID- 16650837
TI  - Cellular iron concentrations directly affect the expression levels of
      norepinephrine transporter in PC12 cells and rat brain tissue.
AB  - Neurological development and functioning are adversely affected by iron
      deficiency in early life. Iron-deficient rats are known to have elevations in
      extracellular DA and NE, suggesting alterations in reuptake of these monoamines.
      To explore possible mechanisms by which cellular iron concentrations may alter NE
      transporter functioning, we utilized NET expressing PC12 cells and iron-deficient
      rats to explore the relationship between NET protein and mRNA expression patterns
      and iron concentrations. Treatment of PC12 with the iron chelator,
      desferrioxamine mesylate (DFO, 50 microM for 24 h), significantly decreased [3H]
      NE uptake by more than 35% with no apparent change in Km. PC12 cells exposed to
      increasing concentrations of DFO (25-100 microM) exhibited a dose response
      decrease in [3H] NE uptake within 24 h (38-73% of control) that paralleled a
      decrease in cellular NET protein content. Inhibition of protein synthesis with
      cycloheximide resulted in NET disappearance rates from DFO-treated cells greatly
      exceeding the rate of loss from control cells. RT-PCR analysis revealed only a
      modest decrease in NET mRNA levels. Rat brain locus ceruleus and thalamus NET
      mRNA levels were also only modestly decreased (10-15%) despite a 40% reduction in
      regional brain iron. In contrast, NET proteins levels in thalamus and locus
      ceruleus were strongly affected by regional iron deficiency with high
      correlations with iron concentrations (r > 0.94 and r > 0.80 respectively). The
      present findings demonstrate that NET protein concentrations and functioning are
      dramatically reduced with iron deficiency; the modest effect on mRNA levels
      suggests a stronger influence on NET trafficking and degradation than on protein
      synthesis.

PMID- 16650838
TI  - Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative
      stress and injury in the gerbil hippocampus.
AB  - Increased production of reactive oxygen species (ROS) following cerebral ischemia
      reperfusion (I/R) is an important underlying cause for neuronal injury leading to
      delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for
      NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase
      inhibitor can protect against ischemia-induced ROS generation and decrease DND.
      Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral
      common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as
      a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30
      min prior to ischemia significantly attenuated the early increase in HNE in
      hippocampus measured at 3 h after I/R. Apocynin also protected against I/R
      induced neuronal degeneration and DND, oxidative DNA damage, and glial cell
      activation. Taken together, the neuroprotective effects of apocynin against ROS
      production during early phase of I/R and subsequent I/R-induced neuronal damage
      provide strong evidence that inhibition of NADPH oxidase could be a promising
      therapeutic mechanism to protect against stroke damage in the brain.

PMID- 16650839
TI  - Cardiac ankyrins: Essential components for development and maintenance of
      excitable membrane domains in heart.
AB  - Ankyrins are intracellular proteins required for the biogenesis and maintenance
      of membrane domains in both excitable and non-excitable cells. Ankyrin family
      polypeptides have been implicated in the targeting and stabilization of membrane
      proteins including ion channels, transporters, exchangers and cell adhesion
      molecules in diverse tissues and cell types including the erythrocyte, kidney,
      lung and brain. Dysfunction in ankyrin-based pathways has previously been linked
      to abnormalities in vertebrate physiology including spherocytosis and anemia,
      ataxia and axonal degeneration. Recent findings have illuminated the importance
      of ankyrin-based pathways in excitable cells of the heart. Specifically, two
      ankyrin gene products, 220-kDa ankyrin-B and 190-kDa ankyrin-G, have been
      implicated in the targeting of structurally diverse membrane ion channels and
      transporters to excitable membrane domains in cardiomyocytes. Moreover, findings
      in humans and mice have determined the critical nature of ankyrin-based pathways
      for normal cardiac excitability. Reduction of ankyrin-B expression levels in mice
      or the presence of ankyrin-B loss-of-function mutations in humans leads to
      'ankyrin-B syndrome', a cardiac disease with a spectrum of clinical presentations
      including bradycardia, ventricular tachycardia and sudden cardiac death in
      response to catecholaminergic stimuli. Ankyrin-G is required for expression of
      the major cardiac voltage-gated Na(v) channel, Na(v)1.5, at specialized cardiac
      membrane domains. Human variants in SCN5A (encodes Na(v)1.5) that block Na(v)1.5
      interaction with ankyrin-G lead to loss of Na(v)1.5 membrane expression and
      Brugada syndrome. Together, these recent findings in heart reinforce the
      importance of ankyrin-based pathways for normal vertebrate physiology and raise
      exciting new questions regarding the cellular roles for ankyrin polypeptides in
      cardiac and other excitable cells. While ankyrins have only been recently
      identified in heart, our current understanding suggests that elucidating the
      roles of ankyrins in organizing and targeting protein complexes to excitable
      membrane domains will yield important insights into the molecular basis of
      cardiac arrhythmias.

PMID- 16650840
TI  - Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow
      in chronic heart failure rabbits.
AB  - OBJECTIVES: We investigated whether Angiotensin II (Ang II) modulates peripheral
      chemoreflex function through carotid body (CB) chemoreceptors in chronic heart
      failure (CHF). METHODS: We measured renal sympathetic nerve activity (RSNA) in
      response to graded hypoxia before and after intravenous administration of Ang II
      (20 ng/kg/min, i.v. 30 min) or AT1 receptor antagonist (L-158,809, 0.33 mg/kg,
      i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the
      effects of Ang II (100 pM) and L-158,809 (1 microM) on CB chemoreceptor activity
      in vascularly isolated-perfused CB preparations from sham and CHF rabbits.
      RESULTS: Ang II enhanced hypoxia-induced RSNA increases in sham rabbits but not
      in CHF rabbits. Conversely, L-158,809 attenuated hypoxia-induced responses in
      RSNA in CHF rabbits but not in sham rabbits. Using RT-PCR, Western blotting, and
      immunocytochemistry, we found that the mRNA and protein expression of AT1
      receptor in the CB from CHF rabbits were greater than that in sham rabbits. CB
      chemoreceptor afferent activity during normoxia and graded hypoxia was increased
      in CHF rabbits compared with sham rabbits. Ang II increased the response of CB
      chemoreceptors to hypoxia in sham rabbits but not CHF rabbits. L-158,809
      decreased CB chemoreceptor responses to hypoxia in CHF rabbits but not in sham
      rabbits. CONCLUSIONS: These results indicate that elevation of Ang II and
      concomitant upregulation of AT1 receptor in the CB contribute to the increased CB
      chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.

PMID- 16650841
TI  - Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and
      melanocyte development.
AB  - The requirement for SOX10 and endothelin-3/EDNRB signalling pathway during
      enteric nervous system (ENS) and melanocyte development, as well as their
      alterations in Waardenburg-Hirschsprung disease (hypopigmentation, deafness and
      absence of enteric ganglia) are well established. Here, we analysed the genetic
      interactions between these genes during ENS and melanocyte development. Through
      phenotype analysis of Sox10;Ednrb and Sox10;Edn3 double mutants, we show that a
      coordinate and balanced interaction between these molecules is required for
      normal ENS and melanocyte development. Indeed, double mutants present with a
      severe increase in white spotting, absence of melanocytes within the inner ear,
      and in the stria vascularis in particular, and more severe ENS defects. Moreover,
      we show that partial loss of Ednrb in Sox10 heterozygous mice impairs
      colonisation of the gut by enteric crest cells at all stages observed. However,
      compared to single mutants, we detected no apoptosis, cell proliferation or
      overall neuronal or glial differentiation defects in neural crest cells within
      the stomach of double mutants, but apoptosis was increased in vagal neural crest
      cells outside of the gut. These data will contribute to the understanding of the
      molecular basis of ENS, pigmentation and hearing defects observed in mouse
      mutants and patients carrying SOX10, EDN3 and EDNRB mutations.

PMID- 16650842
TI  - Correlations between mercury concentrations in umbilical cord tissue and other
      biomarkers of fetal exposure to methylmercury in the Japanese population.
AB  - Methylmercury (MeHg) is one of the most risky substances to affect humans through
      fish consumption, and the fetus is known to be in the most susceptible group. Our
      objective in this study is to examine the relationships of total mercury (THg)
      and MeHg concentrations between umbilical cord tissue and other tissues as
      biomarkers of fetal exposure to MeHg in the Japanese population. In total, 116
      paired samples were collected in three Japanese districts, the Tsushima Islands,
      Fukuoka City, and Katsushika ward of metropolitan Tokyo. THg was measured for
      hair and THg and MeHg were measured in cord tissues, maternal blood, and cord
      blood. The relationships among tissues in Hg concentrations were similar among
      districts. Therefore, we analyzed the relationships using all the samples. More
      than 90% of Hg in cord tissue, cord blood, and maternal blood was MeHg. THg and
      MeHg in cord blood was about two times higher than in maternal blood. A strong
      correlation was found between THg and MeHg in cord tissue. The cord tissue THg
      and MeHg showed a strong correlation with cord blood Hg, which is recognized as
      the best biomarker for fetal exposure to MeHg. The findings of this study
      indicate the significance of cord tissue THg and MeHg as biomarkers for fetal
      exposure to MeHg at parturition.

PMID- 16650843
TI  - Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and
      whole blood.
AB  - Some chalcones, such as hydroxychalcones have been reported previously to inhibit
      major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2)
      (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species
      production by suppressing inducible enzyme expression via inhibition of the
      mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of
      critical transcription factors. In this report, the effects of cardamonin (2',4'
      dihydroxy-6'-methoxychalcone), a chalcone that we have previously isolated from
      Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly
      used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7
      cells and whole blood. Cardamonin inhibited NO and PGE(2) production from
      lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with
      IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of
      thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the
      COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2)
      via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively.
      Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in
      its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the
      generation of intracellular reactive oxygen species and secretion of TNF-alpha
      from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8
      microM and 4.6 microM, respectively. However, cardamonin was a moderate inhibitor
      of lipoxygenase activity when tested in an enzymatic assay system, in which not a
      single concentration tested was able to cause an inhibition of more than 50%. Our
      results suggest that cardamonin acts upon major pro-inflammatory mediators in a
      similar fashion as described by previous work on other closely related synthetic
      hydroxychalcones and strengthens the conclusion of the importance of the methoxyl
      moiety substitution on the 4' or 6' locations of the A benzene ring.

PMID- 16650844
TI  - A comparative study of the action of tolperisone on seven different voltage
      dependent sodium channel isoforms.
AB  - The specific, acute interaction of tolperisone, an agent used as a muscle
      relaxant and for the treatment of chronic pain conditions, with the Na(v1.2),
      Na(v1.3), Na(v1.4), Na(v1.5), Na(v1.6), Na(v1.7), and Na(v1.8) isoforms of
      voltage dependent sodium channels was investigated and compared to that of
      lidocaine. Voltage dependent sodium channels were expressed in the Xenopus laevis
      oocyte expression system and sodium currents were recorded with the two electrode
      voltage clamp technique. Cumulative dose response relations revealed marked
      differences in IC(50) values between the two drugs on identical isoforms, as well
      as between isoforms. A detailed kinetic analysis uncovered that tolperisone as
      well as lidocaine exhibited their blocking action not only via state dependent
      association/dissociation with voltage dependent sodium channels, but a
      considerable fraction of inhibition is tonic, i.e. permanent and basic in nature.
      Voltage dependent activation was affected to a minor extent only. A shift in
      steady-state inactivation to more negative potentials could be observed for most
      drug/isoform combinations. The contribution of this shift to overall block was,
      however, small at drug concentrations resulting in considerable overall block.
      Recovery from inactivation was affected notably by both drugs. Lidocaine
      application led to a pronounced prolongation of the time constant of the fast
      recovery process for the Na(v1.3), Na(v1.5), and Na(v1.7) isoforms, indicating
      common structural properties in the local anesthetic receptor site of these three
      proteins. Interestingly, this characteristic drug action was not observed for
      tolperisone.

PMID- 16650845
TI  - Effect of desferrioxamine, a strong iron (III) chelator, on 1-methyl-4
      phenylpyridinium ion (MPP+)-induced hydroxyl radical generation in the rat
      striatum.
AB  - The present study was examined that the desferrioxamine, a strong iron (III)
      chelator, enhanced 1 methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl
      radical (*OH) generation in the extracellular fluid of caudate nucleus
      anesthetized rats. Rats were anesthetized, and sodium salicylate in Ringer's
      solution (0.5 nmol/microl/min) was infused through a microdialysis probe to
      detect the generation of *OH as reflected by the non-enzymatic formation of 2,3
      dihydroxybenzoic acid (DHBA) in the striatum. Induction of desferrioxamine (50
      microM) drastically increased the formation of *OH trapped as 2,3-DHBA by the
      action of MPP+, as compared with MPP+-only-treated animals. Although
      desferrioxamine did not change the levels of MPP+-induced dopamine, a marked
      elevation of *OH formation trapped as 2,3-DHBA was observed. When corresponding
      experiments were performed with reserpinized animals, the level of dopamine and
      2,3-DHBA drastically decreased. However, the level of dopamine did not change,
      but desferrioxamine significantly increased the level of 2,3-DHBA in reserpinized
      animals. Iron (III) decreased MPP+-induced 2,3-DHBA formations in the presence of
      dopamine (10 microM). Moreover, when iron (II) was administered to
      desferrioxamine-treated animals, a marked elevation of 2,3-DHBA was observed,
      compared with MPP+-only-treated animals, that showed a positive linear
      correlation between iron (II) and *OH formation trapped as 2,3-DHBA (R2=0.981) in
      the dialysate. The present study indicates that the suppression of MPP+-induced
      *OH formation by iron (III) may play a key role in protective effect of iron
      (III) on the rat brain.

PMID- 16650846
TI  - Role of bradykinin B2 receptors in the modulation of the peristaltic reflex of
      the guinea pig isolated ileum.
AB  - Bradykinin is well known to have a biphasic action to contract and relax
      gastrointestinal tissue. However, no studies have investigated the potential
      action of bradykinin to affect the peristaltic reflex. In the present study,
      serosally applied bradykinin (1-1000 nM) and the bradykinin B2 receptor agonist,
      kallidin (1-1000 nM), had inhibitory actions and increased the pressure threshold
      for peristalsis (maximum changes seen at 1000 nM were approximately 60 Pa), as
      did morphine (IC50=22.3+/-4.8 nM; maximum increase in the pressure threshold was
      approximately 130 Pa). Conversely, the B1 kinin receptor agonist, [des-Arg9]
      bradykinin (1-1000 nM), had no effect (P>0.05). Two potent B2 receptor
      antagonists, FR173657 (1 and 100 nM) and icatibant (10 nM), significantly
      antagonized the inhibitory action of serosally applied bradykinin on peristalsis
      (P<0.01), whilst the B1 receptor antagonist, Lys-[des-Arg9, Leu8]-bradykinin (100
      nM) was inactive (P>0.05). In comparison, 5-hydroxytryptamine (1-1000 nM)
      facilitated peristalsis (EC50=37.7+/-23.0 nM; maximum reduction of the pressure
      threshold for peristalsis was approximately 76 Pa), as did FR173657 at 100 nM
      (reducing the pressure threshold for peristalsis by approximately 15 Pa; P<0.05)
      but icatibant at 10 nM was inactive (P>0.05). The results indicate that
      bradykinin B2 receptors mediate an inhibition of peristalsis in the guinea pig
      isolated ileum.

PMID- 16650847
TI  - Weight-dependent changes of immune system in adipose tissue: importance of
      leptin.
AB  - Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly
      altered in obesity. Leptin, production of which is correlated to fat mass, is
      strongly involved in the relationships between adipose tissues and immune system.
      We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine
      whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2)
      leptin was involved in such relationships. Immunohistological analyses revealed a
      tight relationship between the T and NK lymphocytes of the stromal vascular
      fraction and adipocytes. We identified a significant negative and positive
      correlation between EPI weight and the percentage of NK and total T cells
      respectively by cytofluorometric analyses. The NK and ancestral gammadelta T cell
      contents were directly dependent of leptin since they increased significantly in
      high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to
      control. By contrast, the alphabeta T cell content seemed independent of leptin
      because their percentages increased significantly with the EPI weight whatever
      the type of mice (control, HF, ob/ob). The present study suggests that adipose
      tissues present, according to their localization, different immunological
      mechanisms that might be involved in the regulation of adipose cells functions
      and proliferations.

PMID- 16650848
TI  - IL4/PGE2 induction of an enlarged early endosomal compartment in mouse
      macrophages is Rab5-dependent.
AB  - The endosomal compartment and the plasma membrane form a complex partnership that
      controls signal transduction and trafficking of different molecules. The
      specificity and functionality of the early endocytic pathway are regulated by a
      growing number of Rab GTPases, particularly Rab5. In this study, we demonstrate
      that IL4 (a Th-2 cytokine) and prostaglandin E2 (PGE2) synergistically induce
      Rab5 and several Rab effector proteins, including Rin1 and EEA1, and promote the
      formation of an enlarged early endocytic (EEE) compartment. Endosome enlargement
      is linked to a substantial induction of the mannose receptor (MR), a well
      characterized macrophage endocytic receptor. Both MR levels and MR-mediated
      endocytosis are enhanced approximately 7-fold. Fluid-phase endocytosis is also
      elevated in treated cells. Light microscopy and fractionation studies reveal that
      MR colocalizes predominantly with Rab5a and partially with Rab11, an endosomal
      recycling pathway marker. Using retroviral expression of Rab5a:S34N, a dominant
      negative mutant, and siRNA Rab5a silencing, we demonstrate that Rab5a is
      essential for the large endosome phenotype and for localization of MR in these
      structures. We speculate that the EEE is maintained by activated Rab5, and that
      the EEE phenotype is part of some macrophage developmental program such as cell
      fusion, a characteristic of IL4-stimulated cells.

PMID- 16650849
TI  - Study of the enantiomeric separation of oxfendazole and cetirizine using
      subcritical fluid chromatography on an amylose-based column.
AB  - The enantiomeric separation of cetirizine and oxfendazole on a Chiralpak AD
      column using subcritical fluid chromatography has been studied in this work. The
      enantioseparation of cetirizine was only possible when 2-propanol was used as a
      modifier, obtaining better results in presence of the additives triethylamine
      (TEA) and trifluoroacetic acid (TFAA). On the contrary, 2-propanol provided the
      lowest enantioresolutions for oxfendazole, in this case the best results in terms
      of high resolution and short analysis time were obtained with ethanol. The study
      of the temperature effect revealed that in the case of cetirizine using 2
      propanol, and oxfendazole using methanol, the separation was enthalpy-driven and
      the isoelution temperature was above the working range. Using ethanol or 2
      propanol, the results showed that the oxfendazole enantioseparation was
      entropically driven and the isoelution temperatures were below the range studied.

PMID- 16650850
TI  - Simultaneous determination of sorbic and benzoic acids in food dressing by
      headspace solid-phase microextraction and gas chromatography.
AB  - A facile headspace solid-phase microextraction (HS-SPME) procedure using 85
      microm polyacrylate (PA) fiber is presented for the simultaneous determination of
      preservatives (sorbic and benzoic acids) in food dressing, including Thousand
      Island Dressing, HellMANN'S Salad Dressing and Tomato Ketchup, by gas
      chromatography (GC) with flame ionization detector (FID). The method presented
      preserves the advantages typical of HS-SPME such as simplicity, low intensity of
      labor, low cost and solvent free. The main factors affecting the HS-SPME process,
      such as extraction temperature and time, desorption temperature and time, the
      acidity and salt concentration of the solution, were optimized. Limits of
      detection (LODs) of the method were 2.00 microg/L for sorbic acid and 1.22
      microg/L for benzoic acid. Relative standard deviations (RSDs) for quintuplicate
      analyses at three concentration levels of 0.10, 2.0 and 20 mg/L ranged between
      3.86 and 14.8%. The method also showed good linearity n a range from 0.02 to 40
      mg/L with correlation coefficients (R2) of 0.9986 for sorbic acid and 0.9994 for
      benzoic acid. Recoveries for the two analytes in all the samples tested ranged
      from 83.44 to 113.2%. Practical applicability was demonstrated through the
      simultaneous determination of sorbic and benzoic acids in the three complex
      samples.

PMID- 16650851
TI  - High-speed counter-current chromatography for the study of defense metabolites in
      wheat. Characterization of 5,6-O-methyl trans-aconitic acid.
AB  - High-speed counter-current chromatography (HSCCC) methods were developed for the
      study of induced defense metabolites in wheat (Triticum aestivum) against powdery
      mildew (Blumeria graminis f. sp. tritici). A single HSCCC purification step
      afforded extraction of mg-quantities of an induced compound with antifungal
      activity. Subsequent LC-MS and NMR analyses have led to the characterization of
      5,6-O-methyl trans-aconitic acid, the first such report of this compound in a
      plant species. The inducible nature of aconitic acid was evidenced by comparing
      the metabolite profiles of leaf extracts from plants treated or not with soluble
      silicon and infected or not with powdery mildew. In a second step, dual-mode
      HSCCC was used to enhance the separation of other forms of aconitic acid in
      wheat. Based on these results, it was concluded that 5,6-O-methyl trans-aconitic
      acid plays an important role as a defense molecule in wheat plants and that HSCCC
      is a powerful separation method for purifying such compounds from complex plant
      pathogen interactions.

PMID- 16650852
TI  - Novel hydrophobic interaction chromatography matrix for specific isolation and
      simple elution of immunoglobulins (A, G, and M) from porcine serum.
AB  - A new, highly acetylated agarose matrix (HA-Sepharose) was synthesized and used
      as a hydrophobic interaction chromatography (HIC) medium to specifically isolate
      immunoglobulins (Igs) from porcine serum. Recovery of Igs was in a single step
      and under mild conditions. HA-Sepharose adsorption was studied in terms of salt,
      gel acetylation time, flow rate, and protein concentration on the loading buffer.
      At 0.5 M Na2SO4, control with unmodified Sepharose retained a small fraction
      (0.70 mg/mL of matrix) of serum albumin. On the contrary HA-Sepharose retained
      primary Igs (IgA, IgG, and 53% of IgM) as revealed by sodium dodecyl sulphate 10%
      polyacrylamide gel electrophoresis (SDS-PAGE), quantitative radial
      immunodiffusion and immunodetection. At a flow rate of 1 mL/min, the HA-Sepharose
      column capacity (3.9 mg/mL of matrix) was similar to the reported capacity for
      the commercial thiophilic T-gel. However, HA-Sepharose showed higher recovery of
      IgA and IgM than the T-gel in the same salt conditions, clearly an advantage in
      terms of immunoglobulin recovery strategies. Acetylation changed the matrix
      adsorption from albumin to immunoglobulins; thus, the highly acetylated gel
      rendered recoveries of Igs from unprocessed porcine serum practically free of
      albumin.

PMID- 16650853
TI  - Structural basis of carbohydrate transfer activity by human UDP-GalNAc:
      polypeptide alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T10).
AB  - Mucin-type O-glycans are important carbohydrate chains involved in
      differentiation and malignant transformation. Biosynthesis of the O-glycan is
      initiated by the transfer of N-acetylgalactosamine (GalNAc) which is catalyzed by
      UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts).
      Here we present crystal structures of the pp-GalNAc-T10 isozyme, which has
      specificity for glycosylated peptides, in complex with the hydrolyzed donor
      substrate UDP-GalNAc and in complex with GalNAc-serine. A structural comparison
      with uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes
      occur in two loops near the catalytic center upon donor substrate binding, and
      that a distinct interdomain arrangement between the catalytic and lectin domains
      forms a narrow cleft for acceptor substrates. The distance between the catalytic
      center and the carbohydrate-binding site on the lectin beta sub-domain influences
      the position of GalNAc glycosylation on GalNAc-glycosylated peptide substrates. A
      chimeric enzyme in which the two domains of pp-GalNAc-T10 are connected by a
      linker from pp-GalNAc-T1 acquires activity toward non-glycosylated acceptors,
      identifying a potential mechanism for generating the various acceptor
      specificities in different isozymes to produce a wide range of O-glycans.

PMID- 16650854
TI  - Crystal structure of pullulanase: evidence for parallel binding of
      oligosaccharides in the active site.
AB  - The crystal structures of Klebsiella pneumoniae pullulanase and its complex with
      glucose (G1), maltose (G2), isomaltose (isoG2), maltotriose (G3), or
      maltotetraose (G4), have been refined at around 1.7-1.9A resolution by using a
      synchrotron radiation source at SPring-8. The refined models contained 920-1052
      amino acid residues, 942-1212 water molecules, four or five calcium ions, and the
      bound sugar moieties. The enzyme is composed of five domains (N1, N2, N3, A, and
      C). The N1 domain was clearly visible only in the structure of the complex with
      G3 or G4. The N1 and N2 domains are characteristic of pullulanase, while the N3,
      A, and C domains have weak similarity with those of Pseudomonas isoamylase. The
      N1 domain was found to be a new type of carbohydrate-binding domain with one
      calcium site (CBM41). One G1 bound at subsite -2, while two G2 bound at -1
      approximately -2 and +2 approximately +1, two G3, -1 approximately -3 and +2
      approximately 0', and two G4, -1 approximately -4 and +2 approximately -1'. The
      two bound G3 and G4 molecules in the active cleft are almost parallel and
      interact with each other. The subsites -1 approximately -4 and +1 approximately
      +2, including catalytic residues Glu706 and Asp677, are conserved between
      pullulanase and alpha-amylase, indicating that pullulanase strongly recognizes
      branched point and branched sugar residues, while subsites 0' and -1', which
      recognize the non-reducing end of main-chain alpha-1,4 glucan, are specific to
      pullulanase and isoamylase. The comparison suggested that the conformational
      difference around the active cleft, together with the domain organization,
      determines the different substrate specificities between pullulanase and
      isoamylase.

PMID- 16650855
TI  - Evidence that membrane insertion of the cytosolic domain of Bcl-xL is governed by
      an electrostatic mechanism.
AB  - Signals from different cellular networks are integrated at the mitochondria in
      the regulation of apoptosis. This integration is controlled by the Bcl-2
      proteins, many of which change localization from the cytosol to the mitochondrial
      outer membrane in this regulation. For Bcl-xL, this change in localization
      reflects the ability to undergo a conformational change from a solution to
      integral membrane conformation. To characterize this conformational change,
      structural and thermodynamic measurements were performed in the absence and
      presence of lipid vesicles with Bcl-xL. A pH-dependent model is proposed for the
      solution to membrane conformational change that consists of three stable
      conformations: a solution conformation, a conformation similar to the solution
      conformation but anchored to the membrane by its C-terminal transmembrane domain,
      and a membrane conformation that is fully associated with the membrane. This
      model predicts that the solution to membrane conformational change is independent
      of the C-terminal transmembrane domain, which is experimentally demonstrated. The
      conformational change is associated with changes in secondary and, especially,
      tertiary structure of the protein, as measured by far and near-UV circular
      dichroism spectroscopy, respectively. Membrane insertion was distinguished from
      peripheral association with the membrane by quenching of intrinsic tryptophan
      fluorescence by acrylamide and brominated lipids. For the cytosolic domain, the
      free energy of insertion (DeltaG degrees x) into lipid vesicles was determined to
      be -6.5 kcal mol(-1) at pH 4.9 by vesicle binding experiments. To test whether
      electrostatic interactions were significant to this process, the salt dependence
      of this conformational change was measured and analyzed in terms of Gouy-Chapman
      theory to estimate an electrostatic contribution of DeltaG degrees el
      approximately -2.5 kcal mol(-1) and a non-electrostatic contribution of DeltaG
      degrees nel approximately -4.0 kcal mol(-1) to the free energy of insertion,
      DeltaG degrees x. Calcium, which blocks ion channel activity of Bcl-xL, did not
      affect the solution to membrane conformational change more than predicted by
      these electrostatic considerations. The lipid cardiolipin, that is enriched at
      mitochondrial contact sites and reported to be important for the localization of
      Bcl-2 proteins, did not affect the solution to membrane conformational change of
      the cytosolic domain, suggesting that this lipid is not involved in the
      localization of Bcl-xL in vivo. Collectively, these data suggest the solution to
      membrane conformational change is controlled by an electrostatic mechanism. Given
      the distinct biological activities of these conformations, the possibility that
      this conformational change might be a regulatory checkpoint for apoptosis is
      discussed.

PMID- 16650856
TI  - Dynamic flexibility of double-stranded RNA activated PKR in solution.
AB  - PKR, an interferon-induced double-stranded RNA activated serine-threonine kinase,
      is a component of signal transduction pathways mediating cell growth control and
      responses to stress and viral infection. Analysis of separate PKR functional
      domains by NMR and X-ray crystallography has revealed details of PKR RNA binding
      domains and kinase domain, respectively. Here, we report the structural
      characteristics, calculated from biochemical and neutron scattering data, of a
      native PKR fraction with a high level of autophosphorylation and constitutive
      kinase activity. The experiments reveal association of the protein monomer into
      dimers and tetramers, in the absence of double-stranded RNA or other activators.
      Low-resolution structures of the association states were obtained from the large
      angle neutron scattering data and reveal the relative orientation of all protein
      domains in the activated kinase dimer. Low-resolution structures were also
      obtained for a PKR tetramer-monoclonal antibody complex. Taken together, this
      information leads to a new model for the structure of the functioning unit of the
      enzyme, highlights the flexibility of PKR and sheds light on the mechanism of PKR
      activation. The results of this study emphasize the usefulness of low-resolution
      structural studies in solution on large flexible multiple domain proteins.

PMID- 16650857
TI  - Structure-stability-activity relationship in covalently cross-linked N-carbamoyl
      D-amino acid amidohydrolase and N-acylamino acid racemase.
AB  - N-Acylamino acid racemase (NAAAR) and N-carbamoyl-D-amino-acid amidohydrolase (D
      NCAase) are important biocatalysts for producing enantiopure alpha-amino acids.
      NAAAR forms an octameric assembly and displays induced fit movements upon
      substrate binding, while D-NCAase is a tetramer that does not change conformation
      in the presence of a ligand. To investigate the effects of introducing
      potentially stabilizing S-S bridges in these different multimeric enzymes,
      cysteine residues predicted to form inter or intra-subunit disulfide bonds were
      introduced by site-directed mutagenesis. Inter-subunit S-S bonds were formed in
      two NAAAR variants (A68C-D72C and P60C-Y100C) and two d-NCAase variants (A302C
      and P295C-F304C). Intra-subunit S-S bonds were formed in two additional NAAAR
      variants (E149C-A182C and V265C). Crystal structures of NAAARs variants show
      limited deviations from the wild-type overall tertiary structure. An apo A68C
      D72C subunit differs from the wild-type enzyme, in which it has an ordered lid
      loop, resembling ligand-bound NAAAR. The structures of A222C and A302C D-NCAases
      are nearly identical to the wild-type enzyme. All mutants with inter-subunit
      bridges had increases in thermostability. Compared with the wild-type enzyme,
      A68C-D72C NAAAR showed similar kcat/Km ratios, whereas mutant D-NCAases
      demonstrated increased kcat/Km ratios at high temperatures (A302C: 4.2-fold at 65
      degrees C). Furthermore, molecular dynamic simulations reveal that A302C
      substantially sustains the fine-tuned catalytic site as temperature increases,
      achieving enhanced activity.

PMID- 16650858
TI  - Crystal structures of SnoaL2 and AclR: two putative hydroxylases in the
      biosynthesis of aromatic polyketide antibiotics.
AB  - SnoaL2 and AclR are homologous enzymes in the biosynthesis of the aromatic
      polyketides nogalamycin in Streptomyces nogalater and cinerubin in Streptomyces
      galilaeus, respectively. Evidence obtained from gene transfer experiments
      suggested that SnoaL2 catalyzes the hydroxylation of the C-1 carbon atom of the
      polyketide chain. Here we show that AclR is also involved in the production of 1
      hydroxylated anthracyclines in vivo. The three-dimensional structure of SnoaL2
      has been determined by multi-wavelength anomalous diffraction to 2.5A resolution,
      and that of AclR to 1.8A resolution using molecular replacement. Both enzymes are
      dimers in solution and in the crystal. The fold of the enzyme subunits consists
      of an alpha+beta barrel. The dimer interface is formed by packing of the beta
      sheets from the two subunits against each other. In the interior of the
      alpha+beta barrel a hydrophobic cavity is formed that most likely binds the
      substrate and harbors the active site. The subunit fold and the architecture of
      the active site in SnoaL2 and AclR are similar to that of the polyketide cyclases
      SnoaL and AknH; however, they show completely different quaternary structures. A
      comparison of the active site pockets of the putative hydroxylases AclR and
      SnoaL2 with those of bona fide polyketide cyclases reveals distinct differences
      in amino acids lining the cavity that might be responsible for the switch in
      chemistry. The moderate degree of sequence similarity and the preservation of the
      three-dimensional fold of the polypeptide chain suggest that these enzymes are
      evolutionary related. Members of this enzyme family appear to have evolved from a
      common protein scaffold by divergent evolution to catalyze reactions chemically
      as diverse as aldol condensation and hydroxylation.

PMID- 16650859
TI  - Characterization of a divergent Sec61beta gene in microsporidia.
AB  - The general secretory (Sec) pathway is the main mechanism for protein secretion
      and insertion into endoplasmic reticulum and plasma membrane in prokaryotes and
      eukaryotes. However, the complete genome of the highly specialized microsporidian
      parasite Encephalitozoon cuniculi appears to lack a gene for Sec61beta, one of
      three universally conserved proteins that form the core of the Sec translocon. We
      have identified a putative, highly divergent homologue of Sec61beta in the genome
      of another microsporidian, Antonospora locustae, and used this to identify a
      previously unrecognized Sec61beta in E. cuniculi. The identity of these genes is
      supported by evidence from secondary structure prediction and gene order
      conservation. Their functional conservation is confirmed by expressing both
      microsporidian homologues in yeast, where they are localized to the endoplasmic
      reticulum and rescue a yeast Sec61beta deletion mutant.

PMID- 16650860
TI  - Thermodynamic and kinetic characterization of ligand binding to the purine
      riboswitch aptamer domain.
AB  - Riboswitches are cis-acting genetic regulatory elements found commonly in
      bacterial mRNAs that consist of a metabolite-responsive aptamer domain coupled to
      a regulatory switch. Purine riboswitches respond to intracellular concentrations
      of either adenine or guanine/hypoxanthine to control gene expression. The aptamer
      domain of the purine riboswitch contains a pyrimidine residue (Y74) that forms a
      Watson-Crick base-pairing interaction with the bound purine nucleobase ligand
      that discriminates between adenine and guanine. We sought to understand the
      structural basis of this specificity and the mechanism of ligand recognition by
      the purine riboswitch. Here, we present the 2,6-diaminopurine-bound structure of
      a C74U mutant of the xpt-pbuX guanine riboswitch, along with a detailed
      thermodynamic and kinetic analysis of nucleobase recognition by both the native
      and mutant riboswitches. These studies demonstrate clearly that the pyrimidine at
      position 74 is the sole determinant of purine riboswitch specificity. In
      addition, the mutant riboswitch binds adenine and adenine derivatives well
      compared with the guanine-responsive riboswitch. Under our experimental
      conditions, 2,6-diaminopurine binds the RNA with DeltaH=-40.3 kcal mol(-1),
      DeltaS=-97.6 cal mol(-1)K(-1), and DeltaG=-10.73 kcal mol(-1). A kinetic
      determination of the slow rate (0.15 x 10(5)M(-1)s(-1) and 2.1 x 10(5)mM(-1)s(-1)
      for 2-aminopurine binding the adenine-responsive mutant riboswitch and 7
      deazaguanine-binding guanine riboswitch, respectively) of association under
      varying experimental conditions allowed us to propose a mechanism for ligand
      recognition by the purine riboswitch. A conformationally dynamic unliganded state
      for the binding pocket is stabilized first by the Watson-Crick base pairing
      between the ligand and Y74, and by the subsequent ordering of the J2/3 loop,
      enclosing the ligand within the three-way junction.

PMID- 16650861
TI  - Concerns, dispositions and behaviors of aggressive drivers: what do self
      identified aggressive drivers believe about traffic safety?
AB  - INTRODUCTION: The purpose of this investigation was to identify beliefs, driving
      personality dispositions, and behaviors that distinguish self-defined aggressive
      drivers from non-aggressive drivers. METHOD: Telephone surveys were used to
      identify self-reported aggressive drivers (n=305) who were compared to non
      aggressive drivers (n=1,715) concerning their beliefs, driving behaviors, and
      self-described driving dispositions. RESULTS: Aggressive drivers, compared to non
      aggressive drivers, were less concerned about speeding, aggressive driving, and
      cell phone use while driving, yet were more likely to have had an encounter with
      another aggressive driver. They were also more likely to report that they had
      driven when they knew they had too much to drink, yet they felt less likely that
      they would be stopped by the police. CONCLUSION: Aggressive drivers display many
      dispositions that define them as high risk drivers and public
      information/motivational campaigns alone will likely be ineffective with this
      group of drivers. Strategies that combine visible enforcement with widespread
      publicity campaigns appear to be necessary.

PMID- 16650862
TI  - The peritoneal cavity is a distinct compartment of angiogenic molecular
      mediators.
AB  - OBJECTIVE: This study was designed to analyze porcine plasma and peritoneal fluid
      for concentration differences of angiogenic molecular mediators and to determine
      local peritoneal sites of production of these molecules. BACKGROUND: The
      peritoneum is now recognized as a dynamic cellular membrane with important
      functions, including antigen presentation; transport and movement of fluid,
      solutes, and particulate matter across serosal cavities; and secretion of
      glycosaminoglycans, extracellular matrix proteins, proinflammatory cytokines, and
      growth factors. The mechanisms of the peritoneal response to injury and the
      factors that determine the outcome of the reactive or reparative processes of the
      peritoneum remain poorly defined. METHODS: Domestic swine (n = 12) underwent
      percutaneous diagnostic peritoneal lavage to obtain preincision peritoneal fluid
      for biochemical analysis. Open biopsy samples of parietal peritoneum and omentum
      were obtained for immunochemical and molecular analysis. Vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels were
      quantitated by enzyme-linked immunosorbent assay, and nitrite/nitrate (NOx)
      measured by nonenzymatic assay. Sections of formalin-fixed tissue were stained
      for immunoreactivity to VEGF, bFGF, and nitric oxide synthase (NOS). Frozen
      homogenized peritoneum and omentum were prepared for isolation of protein and
      RNA. An endothelial growth assay was created using human umbilical vein
      endothelial cells cultured with peritoneal fluid with or without anti-VEGF or
      anti-bFGF antibodies. RESULTS: The mean plasma concentrations of VEGF, bFGF, and
      NOx were 20 +/- 5 pg/mL, 35 +/- 9 pg/mL, and 4.5 +/- 1.3 microm, compared with
      mean peritoneal fluid concentrations of 395 +/- 75 pg/mL, 486 +/- 72 pg/mL, and
      35.0 +/- 8.8 mum respectively (P < 0.05 for each molecule). Immunochemistry
      demonstrated VEGF, bFGF, and NOS protein in mesothelium, submesothelium, and
      omentum. The use of Western blotting and reverse transcription polymerase chain
      reaction confirmed peritoneal and omental presence of VEGF and NOS-2. The use of
      endothelial bioassay documented peritoneal fluid angiogenic activity, which was
      inhibited by addition of neutralizing antibody to VEGF or bFGF. CONCLUSION:
      Peritoneal compartmentalization of angiogenic mediators important in wound
      healing, inflammation, and tumor growth suggests that the plasma concentrations
      of these mediators do not reflect their tissue concentrations or local biological
      activity.

PMID- 16650863
TI  - Enhancement of NKT cells and increase in regulatory T cells results in improved
      allograft survival.
AB  - BACKGROUND: Natural killer T (NKT) cells can serve as regulatory cells important
      in peripheral tolerance. In an experimental colitis model, it was shown that
      FK506 enhances the tolerizing effect of regulatory NKT cells induced by oral
      tolerance. We explored whether a subtherapeutic dose of FK506 could enhance the
      tolerizing effect of NKT cells induced by oral administration of donor spleen
      cells (SCs) in the pre-transplant period to prolong heart allograft survival.
      METHODS: Heterotopic heart transplantation was performed from BALB/c to B6 mice.
      The B6 recipients were pre-treated with either BALB/c SCs (2 x 10(7)/mouse), or
      FK506 (1.0 mg/kg/d), or BALB/c SCs + FK506 by gavage every other day for a total
      of five feedings before transplantation. RESULTS: Heart allograft survival was
      only significantly prolonged in the BALB/c SC + FK506 pre-fed mice. This was
      associated with a marked increase of NKT cells in both the liver and spleen of
      the recipients, and most importantly, 7 days after transplantation, an increase
      in CD25+CD4+ T cells expressing CTLA4 in the spleen. CONCLUSIONS: In our model it
      appears that a subtherapeutic dose of FK506 enhanced the tolerizing effect of NKT
      cells induced by oral tolerance, prolonging allograft survival by generating
      CD25+CD4+ CTLA4 T cells. This appears to be an excellent in vivo model to
      generate regulatory T cells to allospecific transplant antigens.

PMID- 16650864
TI  - Tensile strength comparison of small intestinal submucosa body wall repair.
AB  - BACKGROUND: Porcine small intestinal submucosa (SIS) has been studied for body
      wall repair. However, the best method to implant the biological material has not
      been investigated. The objective of this study was to compare tensile strengths
      achieved after healing when SIS was placed using three implant techniques (onlay,
      inlay, underlay) in a porcine model of abdominal wall defect. MATERIALS AND
      METHODS: Twenty female domestic pigs had three abdominal midline sites assigned
      to one of five test groups: SIS implantation using inlay, onlay, or underlay
      technique; sham surgery (sutured midline incision) or normal body-wall control.
      Full-thickness muscle/fascia midline abdominal defects (6 x 4 cm) were surgically
      created and then repaired using eight-layer SIS. Healing was evaluated at 1 and 4
      post-operative months by tensile strength testing and histopathology. RESULTS:
      Hernias were not observed. Tensile strengths were not statistically different
      between the five test groups (P = 0.39) or between months 1 and 4 (P = 0.35). The
      caudal site was stronger than the cranial or middle sites in the 1 month group (P
      < 0.0001). Histologically, healing appeared to progress over time as the repair
      site showed remodeling towards an interlacing fibrous connective tissue pattern.
      CONCLUSIONS: No significant differences in tensile strength were found between
      implant techniques and were not statistically different from sham surgery and
      normal control tissue. This study suggested that SIS healing/remodeling provides
      sufficient tensile strength for the repair of ventral (anterior) abdominal wall
      defects when implanted using any of three common techniques.

PMID- 16650865
TI  - Perivenous application of fibrin glue as external support enhanced adventitial
      adenovirus transfection in rabbit model.
AB  - BACKGROUND: Placement of an external support has been reported to prevent intimal
      hyperplasia of vein grafts. However, it's application limited by potential
      complications. Peri-adventitial gene delivery is a promising alternative therapy
      to reduce intimal hyperplasia, but it is limited by low and transient levels of
      gene transfection. To get more effective inhibition of intimal hyperplasia and to
      avoid the limitations associated with these two approaches, a study was
      undertaken to investigate whether mixing adenovirus with fibrin glue may increase
      the level and prolong the time period of gene expression. METHODS: Right jugular
      vein to common carotid artery interposition grafting was performed in 36 male New
      Zealand white rabbits (2.5-3.0 kg) and the animals were divided into four groups:
      control group (n = 6); fibrin glue group (n = 6); Ad-GAL group (n = 12); fibrin
      glue/Ad-GAL group (n = 12). Commercially available fibrin glue and adenovirus
      expressing the gene for beta-galactosidase (Ad-GAL) was applied separately or in
      mixing around vein grafts. At 7th day and 14th day after implantation, the grafts
      were harvested to evaluate transfection rate. At 28th day the grafts were
      harvested for morphometric analysis. RESULTS: Compared with weak staining in 2.1
      +/- 0.5% in Ad-GAL alone grafts, a high level of beta-Galactosidase staining was
      evident in 13.2 +/- 4.6% in fibrin glue/Ad-GAL grafts at 7th day (P < 0.001). At
      14th day, almost no staining (0%) was detected in Ad-GAL alone grafts. However,
      there was still a relative high level staining (6.3 +/- 3.8%) in fibrin glue/Ad
      GAL grafts (P < 0.001 versus Ad-GAL alone group). At 28th day, a statistically
      significantly decrease in neointimal area (0.68 +/- 0.06 mm(2)versus 1.00 +/-
      0.08 mm(2), P < 0.05) was shown in fibrin glue grafts compared with unsupported
      vein grafts (control group). The same statistically significantly difference was
      also existed in fibrin glue/Ad-GAL group and unsupported group in neointimal area
      (0.66 +/- 0.07 mm(2), P < 0.05). CONCLUSIONS: A novel method of adventitial gene
      delivery using fibrin glue as external support is proposed. Fibrin glue may be an
      ideal candidate for controlled release delivery that would facilitate adventitial
      gene transfer.

PMID- 16650866
TI  - Performance of dynamic and isovolumetric trained skeletal muscle ventricles.
AB  - BACKGROUND: Dynamic training and maintaining muscle tension are important factors
      during skeletal muscle ventricle (SMV) conditioning that may improve SMV
      performance. This study sought to determine the effects of dynamic muscle
      training and progressive SMV resting pressure expansion on SMV pumping
      capability. MATERIALS AND METHODS: SMVs were constructed in 14 goats using the
      left latissimus dorsi muscle. SMVs were conditioned with a 40 ml constant-volume
      isovolumetric implant (n = 5, IsoVol group) or a compliant, pneumatic system that
      allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV
      resting pressure was either progressively increased from 40 to 100 to 120 mmHg (n
      = 5, HiP group) or maintained at 40 mmHg (n = 4, LowP group) during conditioning.
      After 8 to 10 weeks of electrical stimulation conditioning, SMVs were connected
      to a counterpulsation mock circulation system and SMV pumping performance
      evaluated across a range of pressures and stimulation parameters. RESULTS: SMV
      pumping performance was similar in each group. Stroke works generally increased
      with pressure and reached a plateau in all groups above 80 mmHg (120 msec
      contraction approximately 80 mJ/stroke; 480 msec contraction approximately 180
      mJ/stroke). Stroke volumes decreased with pressure except at high stimulation
      levels where loading effects were observed. Chronic changes in SMV volume
      significantly effected pumping performance. CONCLUSIONS: These data suggest that
      acute pumping performance is not different between 8 to 10 weeks of dynamic or
      isovolumetric training if SMV volume is not constrained. A potentially improved
      SMV conditioning protocol is proposed that determines, positions, and maintains
      SMV volume near the initial volume for maximal isovolumetric pressure during
      conditioning.

PMID- 16650867
TI  - Carcinogen-induced DNA double strand break repair in sporadic breast cancer.
AB  - BACKGROUND: Induction of DNA double strand breaks and alterations in the repair
      of these breaks is implicated in breast carcinogenesis. Prior studies have
      demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer
      patients exhibit increased numbers of DNA strand breaks after exposure to
      ionizing radiation, but these studies did not specifically measure DNA double
      strand breaks and it is not known whether chemical carcinogens produce similar
      effects. MATERIALS AND METHODS: PBMC from 32 women undergoing breast surgery were
      genotyped at nine loci of seven DNA repair genes. DNA double strand break repair
      was measured using the neutral comet assay after exposure to ionizing radiation
      (0.5 Gy) or bioactivated benzo[a]pyrene (B[a]P, 5 microM. RESULTS: PBMC from
      breast cancer patients showed higher levels of residual DNA double strand breaks
      30 min after exposure to radiation than PBMC from patients with benign breast
      disease (1.40 times baseline [95% confidence intervals [CI] 1.29-1.51] versus
      1.24 times baseline [95% CI 1.15-1.33], respectively, P = 0.04). The response to
      B[a]P trended in the same direction, but did not reach statistical significance.
      The MGMT K178R variant genotype was associated with improved DNA double strand
      break repair in PBMC exposed to B[a]P. CONCLUSIONS: Reduced repair of radiation
      induced DNA double strand breaks in PBMC is a robust biomarker of breast cancer
      risk. Reduced DNA repair capacity may have a genetic component even in sporadic
      breast cancer.

PMID- 16650868
TI  - Inflammation effects on the electrical properties of atrial tissue and
      inducibility of postoperative atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common complication after cardiac
      surgery. Postoperative atrial fibrillation (PAF) has been shown to increase
      length of stay, morbidity, and mortality. Because the clinical behavior of PAF
      parallels that of inflammation following surgery, we investigated the effect of
      the inflammatory mediator arachidonic acid on the electrical behavior of normal
      atrial tissue in vitro and assessed the efficacy of the topical application of
      anti-inflammatory drugs at suppressing PAF in an animal model. METHODS: To study
      changes in electrical behavior from inflammation, the conduction properties of
      six normal canine right atrial appendages were quantified as a function of the
      direction of impulse propagation with and without 80 mum arachidonic acid. To
      study the effect of topical anti-inflammatory drugs, 24 adult mongrel dogs were
      prepared according to the model of sterile talc pericarditis. Nine dogs received
      talc alone (T), seven received talc combined with 600 mg ibuprofen (T + I), and
      eight received talc combined with 10 mg methylprednisolone (T + M). Three days
      following preparation, programmed electrical stimulation was performed to
      quantify conduction characteristics and to attempt the induction of atrial
      fibrillation (AF). RESULTS: In vitro, arachidonic acid produced an anisotropic
      and rapidly reversible 36.1 +/- 3.4% (P = 0.01) decrease in conduction velocity
      transverse to the long axis only. In vivo, both ibuprofen and methylprednisolone
      significantly reduced the incidence of sustained AF (from 56 to 0% T + I and 12%
      T + M, respectively, P = 0.02). No differences in conduction velocities or
      refractory periods were seen during sinus rhythm among the groups. CONCLUSIONS:
      Acute inflammation as mimicked by arachidonic acid slows conduction
      anisotropically, mainly transverse to the long axis of the atrial myocardial
      fibers. This may set the stage for reentry. Preventing inflammation in vivo by
      the topical application of anti-inflammatory drugs supports this hypothesis,
      suggesting a possible role for inflammation in the genesis of postoperative
      atrial fibrillation and shedding light on the mechanism underlying PAF.

PMID- 16650869
TI  - Intestinal ischemia/reperfusion injury aggravates talc-induced adhesions in rats.
AB  - BACKGROUND: Postoperative intraperitoneal adhesions are the leading cause of
      intestinal obstruction, but the underlying mechanisms remain incompletely
      understood. The aim of the current study was to investigate the involvement of
      intestinal ischemia/reperfusion (I/R) injury in adhesion formation in rats.
      MATERIALS AND METHODS: Rats were subjected to either a dusting of talc (15
      mg/rat) over the entire small intestine or ischemia induced by clamping the
      superior mesenteric artery (SMA) for 30 min followed by reperfusion with or
      without talc dusting. On postoperative days 4, 7, and 14, the scores, lengths,
      and incidence of adhesions were evaluated. In addition, the contractile force of
      the jejunal muscle was measured at 0, 24, 48, and 96 h after the treatments using
      organ bath techniques under bethanechol-stimulated conditions. RESULTS: Talc
      induced mild adhesions in rats. Although I/R injury alone did not produce
      adhesions, it markedly aggravated the talc-induced adhesions, with higher scores
      and longer adhesions on postoperative days 4, 7, and 14. In addition, I/R injury
      caused 75-88% suppression of the circular muscle contractile force and 35-52%
      suppression of the longitudinal muscle contractile force at 24 h after SMA
      occlusion. However, talc did not affect the contractions. CONCLUSIONS: Intestinal
      I/R injury aggravated the talc-induced adhesions, and this consequence might be
      due to the functional suppression of jejunal muscle contractions. This finding
      suggests that intestinal ischemia is an important factor in the etiology of
      postoperative adhesions.

PMID- 16650870
TI  - A single nucleotide polymorphism in the plasma PAF acetylhydrolase gene and risk
      of atherosclerosis in Japanese patients with peripheral artery occlusive disease.
AB  - BACKGROUND: Plasma PAF-acetylhydrolase (PAF-AH) gene polymorphisms (G994 --> T in
      exon 9) and the resulting deficiency of enzyme activity were identified in the
      Japanese population. The objective of this study was to assess the joint effect
      of the polymorphism and hypercholesterolemia on risk of atherosclerosis. METHODS
      AND RESULTS: We performed a case-control study including 150 patients who
      underwent operation for peripheral arterial occlusive disease (PAOD) and 158
      controls matched for age and sex. Genomic DNA was analyzed for the mutant allele
      by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in
      both groups. The patients with multiple atherosclerotic diseases showed higher
      levels of PAF-AH activities than the patients with only peripheral artery
      occlusive disease among normal genotypes. PAOD patients were assessed either with
      or without polymorphism or hypercholesterolemia in regard to accompanying
      coronary artery disease or stroke. The prevalence of the polymorphism was
      significantly more frequent in the patients with PAOD. The plasma PAF-AH activity
      was correlated with total cholesterol and LDL level, and inversely related with
      HDL in normal genotype (GG) PAOD patients. However, neither the correlation nor
      the inverse relation was found in patients with the polymorphism. Patients with
      both hypercholesterolemia and the polymorphisms revealed a relative risk for
      other atherosclerotic disease of 11.5 (6.0-40.3) compared with normal genotype
      and normal lipid level. CONCLUSION: The plasma PAF-AH gene polymorphism and
      hypercholesterolemia may interact and increase the risk of atherosclerosis.

PMID- 16650871
TI  - Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical
      model in the dog.
AB  - PURPOSE: Local recurrence of rectal cancer remains a significant clinical problem
      despite multi-modality therapy. Photodynamic Therapy (PDT) is a cancer treatment
      which generates tumor kill through the production of singlet oxygen in cells
      containing a photosensitizing drug when exposed to laser light of a specific
      wavelength. PDT is a promising modality for prevention of local recurrence of
      rectal cancer for several reasons: tumor cells may selectively retain
      photosensitizer at higher levels than normal tissues, the pelvis after mesorectal
      excision is a fixed space amenable to intra-operative illumination, and PDT can
      generate toxicity in tissues up to 1 cm thick. This study evaluated the safety,
      tissue penetration of 730 nm light, normal tissue toxicity and surgical outcome
      in a dog model of rectal resection after motexafin lutetium-mediated photodynamic
      therapy. METHODS: Ten mixed breed dogs were used. Eight dogs underwent
      proctectomy and low rectal end to end stapled anastomosis. Six dogs received the
      photosensitizing agent motexafin lutetium (MLu, Pharmacyclics, Inc., Sunnyvale,
      CA) of 2 mg/kg preoperatively and underwent subsequent pelvic illumination of the
      transected distal rectum of 730 nm light with light doses ranging from 0.5
      J/cm(2) to 10 J/cm(2) three hours after drug delivery. Two dogs received light,
      but no drug, and underwent proctectomy and low-rectal stapled anastomosis. Two
      dogs underwent midline laparotomy and pelvic illumination. Light penetration in
      tissues was determined for small bowel, rectum, pelvic sidewall, and skin.
      Clinical outcomes were recorded. Animals were sacrificed at 14 days and
      histological evaluation was performed. RESULTS: All dogs recovered uneventfully.
      No dog suffered an anastomotic leak. Severe tissue toxicity was not seen.
      Histological findings at necropsy revealed mild enteritis in all dogs. The
      excitation light penetration depths were 0.46 +/- 0.18, 0.46 +/- 0.15, and 0.69
      +/- 0.39 cm, respectively, for rectum, small bowel, and peritoneum in dogs that
      had received MLu. For control dogs without photosensitizer MLu, the optical
      penetration depths were longer: 0.92 +/- 0.63, 0.67 +/- 0.10, and 1.1 +/- 0.80 cm
      for rectum, small bowel, and peritoneum, respectively. CONCLUSION: Low rectal
      stapled anastomosis is safe when performed with MLu-mediated pelvic PDT in a dog
      model. Significant tissue penetration of 730 nm light into the rectum and pelvic
      sidewall was revealed without generation of significant toxicity or histological
      sequelae. Penetration depths of 730 nm light in pelvic tissue suggest that
      microscopic residual disease of less than 5 mm are likely to be treated
      adequately with MLu-mediated PDT. This approach merits further investigation as
      an adjuvant to total mesorectal excision and chemoradiation for rectal cancer.

PMID- 16650872
TI  - Hospital-based factors predict outcome after carotid endarterectomy.
AB  - OBJECTIVE: Patient, hospital, and surgeon factors affect outcome after carotid
      endarterectomy (CEA). The nature and importance of hospital-specific factors,
      especially those unrelated to procedural volume, that affect post-CEA outcome
      remains poorly defined. We used a statewide database to determine the impact of
      several hospital-associated factors on outcome after CEA. METHODS: Hospital
      factors were established by telephone survey and validated by repeated survey as
      well as by the Connecticut Hospital Association, Connecticut state, and
      individual hospital internet Websites. All CEA in Connecticut non-federal
      hospitals between 1991 and 2002 were examined, including perioperative mortality,
      stroke, and cardiac complications. Multivariable logistic regression was used to
      analyze data. RESULTS: There were 14,288 CEAs performed with 0.5% mortality, 1.3%
      stroke, and 2.4% cardiac complications. The only hospital factor independently
      predictive of perioperative mortality was few number of hospital beds (less than
      132 beds; odds ratio (OR) 2.78, P = 0.032). Factors predictive of perioperative
      stroke included few number of beds (OR 1.96, P = 0.001) and absence of a critical
      pathway (OR 1.39, P = 0.038). Factors predictive of perioperative cardiac
      complications included few number of beds (OR 3.01, P = 0.003), absence of a
      critical pathway (OR 1.50, P = 0.001), and absence of dedicated vascular recovery
      beds (OR 1.35, P = 0.03). Combined mortality, stroke, or cardiac complications
      were independently predicted by few hospital beds (OR 4.58, P = 0.002), absence
      of a critical pathway (OR 1.81, P < or = 0.0001), or inability to perform cardiac
      angiography (OR 3.92, P = 0.024). CONCLUSIONS: Hospital-based factors, such as
      greater bed capacity, use of critical pathways, ability to perform cardiac
      angiography, or presence of a dedicated vascular recovery unit predict reduced
      perioperative mortality, stroke and cardiac complications from CEA. These results
      suggest that hospital-associated factors do impact surgical outcome and that
      surgeons need to optimize these factors, extrinsic to the patient and surgeon, to
      provide maximal quality of care.

PMID- 16650873
TI  - Proteomic analysis of neuroblastoma subtypes in response to mitogen-activated
      protein kinase inhibition: profiling multiple targets of cancer kinase signaling.
AB  - INTRODUCTION: Survival for high-risk neuroblastoma (NB) remains poor despite
      aggressive therapy. Novel therapies are vital for improving prognosis. We
      previously showed differential NB subtype sensitivity to p42/44 mitogen-activated
      protein kinase (ERK/MAPK) pathway inhibition. In this study, we investigated
      proteomic changes associated with resistance or sensitivity to MAPK kinase (MEK)
      inhibition in NB subtypes. MATERIALS AND METHODS: SH-SY5Y (N-type), BE(2)-C (I
      type), and SK-N-AS (S-type) were treated with MEK inhibitor U0126 (10 microM) for
      1 and 24 h. Proteins were extracted from untreated and treated cells and analyzed
      for differential expression by two-dimensional polyacrylamide gel electrophoresis
      (2D-PAGE). Selected polypeptides were extracted from the gel and identified by
      liquid chromatography-linked tandem mass spectrometry (LC-MS/MS). RESULTS: We
      identified 15 proteins that were decreased by 2.5-fold between untreated and 1 h
      treated cells and subsequently up-regulated 5-fold after 24 h drug treatment. N
      type NB (MEK-resistant) showed the least altered proteomic profile whereas the I
      type (MEK-sensitive) and S-type NB (MEK-intermediate) generated significant
      protein changes. The majority of proteins identified were induced by stress.
      CONCLUSIONS: Protein differences exist between MEK inhibitor-treated NB subtypes.
      Identified polypeptides all have roles in mediating cellular stress. These data
      suggest that inhibition of the ERK/MAPK in NB subtypes leads to an intracellular
      stress response. The most resistant NB cell line to MEK inhibitor treatment
      generated the least protective protein profile, whereas the intermediate and most
      sensitive NB cells produced the most stress response. These findings suggest
      stress related protein expression may be targeted in assessing a response to
      ERK/MAPK therapeutics.

PMID- 16650874
TI  - Cortical demyelination in multiple sclerosis: a substrate for cognitive deficits?
AB  - Recent studies highlight cortical demyelinated lesions as a feature of multiple
      sclerosis (MS) pathology, which has received little attention so far. Here, we
      describe that cortical plaques are frequent and widespread, in particular in
      patients with primary or secondary progressive MS. Furthermore, we describe that
      certain cortical areas, such as the cingulated gyrus, the insular cortex and the
      temporobasal cortex, are more affected than others. These data indicate that
      cortical lesions have to be considered as an additional pathological substrate
      for cognitive dysfunction in MS patients.

PMID- 16650875
TI  - Identification of quantitative trait nucleotides that regulate cancer growth: a
      simulation approach.
AB  - A general growth model derived from basic cellular properties can be used to
      describe the dynamic process of cancer growth with mathematical equations. It has
      been recognized that cancer growth is under genetic control, with a multitude of
      interacting genes each segregating in a Mendelian fashion and displaying
      environmental sensitivity. In this article, we integrate the mathematical aspects
      of the pervasive growth model into a statistical framework for the identification
      of quantitative trait nucleotides that underlie cancer growth. This integrative
      framework is constructed with a single nucleotide polymorphism-based haplotype
      blocking analysis. Simulation studies have been performed to demonstrate the
      usefulness of the model. The proposed model provides a generic platform model for
      testing and detecting specific DNA sequence variants that regulates the timing of
      cancer emergence, growth and differentiation.

PMID- 16650876
TI  - A mathematical model for apoptosome assembly: the optimal cytochrome c/Apaf-1
      ratio.
AB  - Apoptosis, a highly conserved form of cell suicide, is regulated by apoptotic
      signals and their transduction with caspases, a family of cystein proteases.
      Caspases are constantly expressed in the normal cells as inactive pro-enzymes.
      The activity of caspase is regulated by the proteolysis. Sequential proteolytic
      reactions of caspases are needed to execute apoptosis. Mitochondrial pathway is
      one of these apoptotic signal pathways, in which caspases are oligomerized into
      characteristic heptamer structure, called apoptosome, with caspase-9 that
      activate the effector caspases for apoptosis. To investigate the dynamics of
      signal transduction pathway regulated by oligomerization, we construct a
      mathematical model for Apaf-1 heptamer assembly process. The model first reveals
      that intermediate products can remain unconverted even after all assemble
      reactions are completed. The second result of the model is that the conversion
      efficiency of Apaf-1 heptamer assembly is maximized when the initial
      concentration of cytochrome c is equal to that of Apaf-1. When the concentration
      of cytochrome c is sufficiently larger or smaller than that of Apaf-1, the final
      Apaf-1 heptamer production is decreased, because intermediate Apaf-1 oligomers
      (tetramers and bigger oligomers), which themselves are unable to form active
      heptamer, accumulate too fast in the cells, choking a smooth production of Apaf-1
      heptamer. Slow activation of Apaf-1 monomers and small oligomers increase the
      conversion efficiency. We also study the optimal number of subunits comprising an
      active oligomer that maximize the conversion efficiency in assembly process, and
      found that the tetramer is the optimum.

PMID- 16650877
TI  - Astragaloside IV improved barrier dysfunction induced by acute high glucose in
      human umbilical vein endothelial cells.
AB  - The purpose of the present study was to examine the effects of astragaloside IV,
      a saponin isolated from Astragalus membranaceus (Fisch) Bge, on the impairment of
      barrier function induced by acute high glucose in cultured human vein endothelial
      cells. High glucose (27.8 mM) induced a decrease in transendothelial electrical
      impedance and an increase in cell monolayer permeability in human umbilical vein
      endothelial cells. Endothelial barrier dysfunction stimulated by high glucose was
      accompanied by translocation and activation of protein kinase C (PKC), the
      redistribution of F-actin and formation of intercellular gaps, suggesting that
      increases in PKC activity and rearrangement of F-actin could be associated with
      endothelial barrier dysfunction induced by acute high glucose. Application of
      astragaloside IV inhibited high glucose-induced endothelial barrier dysfunction
      in a dose-dependent manner, which is compatible with inhibition of PKC
      translocation and improvement of F-actin rearrangements. Western blot analysis
      revealed that high glucose-induced PKC alpha and beta2 overexpression in the
      membrane fraction were significantly reduced by astragaloside IV. These findings
      indicate that astragaloside IV protected endothelial cells from high glucose
      induced barrier impairment by inhibiting PKC activation, as well as improving
      cytoskeleton remodeling.

PMID- 16650878
TI  - Endostatin influences endothelial morphology via the activated ERK1/2-kinase
      endothelial morphology and signal transduction.
AB  - Endostatin, the proteolytic fragment of collagen XVIII, is known to be a potent
      inhibitor of angiogenesis. However, to date, only limited knowledge exists with
      regard to the effects of endostatin on vessel morphology and the underlying
      signaling pathway. The aim of the present work was therefore to determine the
      impact of endostatin and its collagen XV analogue restin on vessel development
      during wound healing and embryonic angio- and vasculogenesis. Time lapse
      experiments and electron microscopy demonstrate similar morphological changes
      evoked by endostatin and the ERK1/2-kinase inhibitor PD98059. Furthermore, we
      show that ERK1/2 phosphorylation, a crucial signaling event in vascular
      morphogenesis, is regulated by endostatin via the protein phosphatase 2A PP2A.
      These findings provide new insight into a key signaling pathway of vascular
      remodeling evoked by a matrix-derived factor.

PMID- 16650879
TI  - Perceptual, premotor and motor factors in the performance of a delayed-reaching
      task by subjects with unilateral spatial neglect.
AB  - We used a computerized delayed-reaching task with a simple reaction time (RT) to
      investigate the visuo-motor and spatio-temporal performance of right brain
      damaged (RBD) patients with unilateral spatial neglect (USN). Fifty-three RBD
      patients (22 with and 31 without USN) and 25 controls performed the tasks. We
      recorded the following data: the first RT (RT-1), which is thought to reflect the
      detection of the target position (the perceptual factor); the second RT (RT-2),
      which represents the initiation of reaching (the motor initiation aspect of
      premotor factors); the movement time (MT), which is hypothesized to reflect the
      "pure" motor component of the task. RBD patients with both USN and hemianopia
      demonstrated significantly longer RTs towards the left than towards the right for
      both the RT-1 and the RT-2. Among the RBD patients without hemianopia, the
      laterality index (left side/right side) of the RT-1 in those with USN was
      significantly greater than in those without USN or the controls. Among the three
      groups, there were no significant differences between the laterality indices of
      either the RT-2s or the MTs. These results suggest that the impairment of
      leftward movement in RBD patients with USN might be caused primarily by a
      perceptual impairment rather than an impairment in motor initiation, and is
      certainly not a "pure" motor impairment.

PMID- 16650880
TI  - The human right to the highest attainable standard of health: new opportunities
      and challenges.
AB  - The health and human rights communities have much in common. Recently, the
      international community has begun to devote more attention to the right to the
      highest attainable standard of health ("the right to health"). Today, this human
      right presents health and human rights professionals with a range of new
      opportunities and challenges. The right to health is enshrined in binding
      international treaties and constitutions. It has numerous elements, including the
      right to health care and the underlying determinants of health, such as adequate
      sanitation and safe water. It empowers disadvantaged individuals and communities.
      If integrated into national and international policies, it can help to establish
      policies that are meaningful to those living in poverty. The author introduces
      his work as the UN Special Rapporteur on the right to health. By way of
      illustration, he briefly considers his interventions on Niger's Poverty Reduction
      Strategy, Uganda's neglected (or tropical or poverty-related) diseases, and the
      recent US-Peru trade negotiations. With the maturing of human rights, health
      professionals have become an indispensable part of the global human rights
      movement. While human rights do not provide magic solutions, they have a
      constructive contribution to make. The failure to use them is a missed
      opportunity of major proportions.

PMID- 16650881
TI  - Selective gene transfer to T lymphocytes using coreceptor-specific [MLV(HIV)]
      pseudotype vectors in a transgenic mouse model.
AB  - The coreceptor usage of HIV-1 envelope proteins (Env) is mainly dependent on a
      defined variable region within the V3-loop of Env. Thus, retroviral vectors
      derived from murine leukemia virus (MLV), which have been pseudotyped with HIV-1
      envelope proteins holding different V3-loops, enable selective gene delivery into
      either CXCR4 or CCR5 positive cultured cells. Here, we tested the distribution of
      CD4/CCR5-tropic [MLV(HIV)]-pseudotype vectors in transgenic mice expressing CD4
      and either CXCR4 or CCR5 of human origin. The specificity of gene transfer was
      analyzed by ex vivo transduction of spleen cells as well as after i.v. or i.p.
      injection of transgenic mice. Expression of the transferred marker gene EGFP and
      vector sequences could be detected exclusively in lymphocytes expressing (hu)CD4
      and (hu)CCR5, whereas MLV vectors pseudotyped with the VSV-G envelope
      glycoprotein mediated gene transfer in mice of all genotypes investigated. These
      data demonstrated that cell-specific gene delivery via [MLV(HIV)]-pseudotyped
      vectors, as previously shown for cultured cells, is also achievable in vivo.

PMID- 16650882
TI  - Local luminance amplitude modulates the interpretation of shape-from-shading in
      textured surfaces.
AB  - The pattern of illumination on an undulating surface can be used to infer its 3-D
      form (shape-from-shading). But the recovery of shape would be invalid if the
      luminance changes actually arose from changes in reflectance. So how does vision
      distinguish variation in illumination from variation in reflectance to avoid
      illusory depth? When a corrugated surface is painted with an albedo texture, the
      variation in local mean luminance (LM) due to shading is accompanied by a similar
      modulation in local luminance amplitude (AM). This is not so for reflectance
      variation, nor for roughly textured surfaces. We used depth mapping and paired
      comparison methods to show that modulations of local luminance amplitude play a
      role in the interpretation of shape-from-shading. The shape-from-shading percept
      was enhanced when LM and AM co-varied (in-phase) and was disrupted when they were
      out of phase or (to a lesser degree) when AM was absent. The perceptual
      differences between cue types (in-phase vs out-of-phase) were enhanced when the
      two cues were present at different orientations within a single image. Our
      results suggest that when LM and AM co-vary (in-phase) this indicates that the
      source of variation is illumination (caused by undulations of the surface),
      rather than surface reflectance. Hence, the congruence of LM and AM is a cue that
      supports a shape-from-shading interpretation.

PMID- 16650883
TI  - Effects of fulvic fractions on the pH-dependent sorption of Cu(II) to kaolinite.
AB  - Sorption of copper on kaolinite in the absence and presence of four fulvic acid
      (FA) fractions fractionated using XAD-8 resin, including F4.8, F7.0, F11.0 and
      Feth fractions (eluted by pH4.8 buffer, pH7.0 buffer, pH11.0 buffer, and ethanol
      (95%), respectively, was investigated by batch experiments. Results showed that
      the binding of Cu(II) by pure kaolinite increased with an increase in pH values.
      The presence of each FA fraction significantly affects the sorption of Cu(II) to
      kaolinite. Below pH 6.3, Cu(II) sorption was pronouncedly promoted after adding
      FA fraction to binary systems, compared to that in pure kaolinite suspensions.
      Magnitude in enhancement of Cu(II) sorption to solid phase, which was caused by
      FA fractions, followed an order of F4.8>F7.0>11.0>Feth. Above pH 6.3, nearly all
      the Cu(II) were removed from solution in pure koalinte system, while a portion of
      Cu(II) left in aqueous phase via formation of dissolved Cu-FA complexes, was
      observed in systems in the presence of FA fractions. The largest Cu(II)
      distribution coefficients (K(d)) between solid phase and aqueous solution at pH
      3.15-5.7, are obtained from the ternary system with F4.8 fraction. The smallest
      K(d) are from system in the presence of Feth fraction. Conversely, over a pH
      range from 5.7 to 7.0, the highest K(d) values are from system with Feth
      fraction. Overall, F4.8 fraction exhibited the greatest effect on Cu(II) pH
      dependent sorption to kaolinite, and Feth fraction had the least. Functional
      groups such as carboxyl, phenolic moieties of FA played the vital role in Cu(II)
      sorption to kaolinite at lower pH conditions, and solubility under neutral
      conditions.

PMID- 16650884
TI  - Development of local knowledge of environmental contamination in Sydney, Nova
      Scotia: environmental health practice from an environmental justice perspective.
AB  - In Sydney, Nova Scotia, from 1901 through 1988 a coke and steel factory operated
      with no pollution controls, depositing over a million tons of particulate matter
      and releasing several thousands of tons of coal tar into the estuary. Previously
      we documented the presence of lead, arsenic and PAHs, in soil above Canadian
      guidelines, and in house dust in the communities surrounding the site [Lambert,
      TW, Lane, S. Lead, arsenic, and polycyclic aromatic hydrocarbons in soil and
      house dust in the communities surrounding the Sydney, Nova Scotia, tar ponds.
      Environ Health Perspect 2004; 112:35-41.]. In this paper we further the research
      by documenting and developing community knowledge with a study of resident's
      observations and experiences of the industrial contamination. We conducted two
      surveys, a quantitative door-to-door survey and qualitative dust interview,
      designed to complement each other and bring together the observations and
      experiences in the different communities to develop the local knowledge. The
      combined methodology uses techniques from both social and physical science, and
      was developed with the cooperation of community members. The research supports
      the proposition that local knowledge adds contextual meaning that complements the
      physical measurement of environmental contaminants, in order to understand the
      complex environment in which people live, and the multiple exposure pathways
      through which they can be affected. Residents in all three communities provided
      vivid observations and detailed experiences of the industrial pollution in their
      community and homes. The local knowledge is consistent with our physical data and
      review of the historical scientific research in Sydney, and supports the
      inference that the community was adversely impacted by the coke and steel
      facility. From a justice perspective, the three communities should be equally
      considered for remediation as part of the 'tar pond remediation policy' rather
      than the current policy of including only a few streets and houses.

PMID- 16650885
TI  - Life cycle assessment of wastewater treatment technologies treating petroleum
      process waters.
AB  - This paper describes the implementation of life cycle assessment to investigate
      the environmental impact of 20 technologies suitable for treating extensive
      volumes of water produced during the oil and gas extraction processes. Data on
      the physical and operational attributes of technologies under consideration were
      assembled and their life cycle environmental impacts estimated over 15 year time
      period. The results were then incorporated in a decision support system which
      allows identification and prioritisation of potential technology combinations
      capable of producing water for nine designated industrial and agricultural end
      uses. In total, more than 618 technology combinations were investigated for their
      environmental impacts. The identification and prioritisation of technologies were
      done on the basis of their environmental and technical performance. This analysis
      showed that dissolved air flotation, absorbents, dual media filtration and
      reverse osmosis technologies offer relatively low environmental impact parts of
      systems for cleaning such process waters. Furthermore, the environmental
      assessment combined within the decision support system has revealed potentially
      valuable indirect downstream "benefits" from effects such as evaporative losses
      from wetlands in terms of the overall environmental impact of a treatment system.

PMID- 16650886
TI  - The effect of primary percutaneous coronary intervention as compared to
      tenecteplase on myeloperoxidase, pregnancy-associated plasma protein A, soluble
      fibrin and D-dimer in acute myocardial infarction.
AB  - INTRODUCTION: Acute coronary reperfusion is accomplished pharmacologically with
      intravenous thrombolytic therapy or mechanically with primary percutaneous
      coronary intervention (PCI). METHODS: We have determined the immediate effects of
      the main coronary reperfusion procedures on the plasma concentrations of
      myeloperoxidase (MPO), pregnancy-associated plasma protein A (PAPP-A), fibrin
      monomer (FM) and D-dimer (DD). We studied a total of 38 patients admitted for ST
      segment elevation infarct (STEMI). 18 patients were given thrombolytic therapy
      with tenecteplase and 20 were treated with primary PCI. RESULTS: The plasma
      concentrations of PAPP-A increased by a factor of six to eight times (p<0.001)
      following both reperfusion therapies. No significant increase was observed for
      MPO by either procedure. DD and FM concentrations both increased significantly
      following thrombolytic therapy, p=0.000, whereas only minor increases, although
      statistically significant for FM (p=0.013), were noted after PCI. DD and FM were
      highly correlated prior to the two treatment regimens (R=0.91), and were still
      highly correlated after PCI (R=0.94) and thrombolytic therapy (R=0.86). No
      correlation was demonstrated between PAPP-A and markers of activated coagulation.
      CONCLUSIONS: This is the first report of a significant rise in the plasma
      concentration of PAPP-A after PCI as compared to thrombolytic treatment (p=0.002)
      and may indicate a greater impact of PCI than that of thrombolytic therapy on
      target coronary plaques.

PMID- 16650887
TI  - L-type calcium channels mediate water intake induced by angiotensin injection
      into median preoptic nucleus.
AB  - Calcium ions are widely accepted as critically important in responses of neurons
      to a stimulus. We have show previously the central involvement of angiotensin II
      (ANGII) in water intake. This study determined whether voltage-dependent calcium
      channels are involved in ANGII-induced behavioral drinking implicating nitrergic
      mechanism. The antidipsogenic actions of L-type calcium channel antagonists
      nifedipine, on ANGII-induced drinking behavior were studied when it is injected
      into the median preoptic nucleus (MnPO). The influence of nitric oxide (NO) on
      nifedipine antidipsogenic action was also studied by utilizing the N(W)-nitro-L
      arginine methyl ester (L-NAME) a constitutive nitric oxide synthase inhibitor
      constitutive (cNOSI) and 7-nitroindazol (7-NIT) a specific neuronal nitric oxide
      synthase inhibitor (nNOSI) and L-arginine a NO donor. Rats 200-250 g, with
      cannulae implanted into MnPO, pre-treated into MnPO with either nifedipine,
      followed by ANGII, drank significantly less water than controls during the first
      15 min after injection. However, L-NAME potentiated the dipsogenic effect of
      ANGII that is blocked by prior injection of nifedipine and L-arginine. 7-NIT
      injected prior to ANGII into MnPO also potentiated the dipsogenic effect of ANGII
      but with a less intensity than L-NAME that it is also blocked by prior injection
      of nifedipine. The results described in this paper provide evidence that calcium
      channels play important roles in the ANGII-induced behavioral water intake. The
      structures containing NO in the brain such as MnPO include both endothelial cells
      and neurons might be responsible for the influence of nifedipine on dipsogenic
      effect of ANGII. These data shows the correlation between L-type calcium channel
      and a free radical gas NO produced endogenously from amino acids L-arginine by
      endothelial and neuronal NO synthase in the control of ANGII-dipsogenic effect.
      This suggests that an L-type calcium channel participates in both short- and
      longer-term neuronal actions of ANGII by nitrergic way.

PMID- 16650888
TI  - Neuroendocrine and reproductive aspects of adult male rats exposed neonatally to
      an antiestrogen.
AB  - The present study was designed to investigate the effects of a single dose of an
      estrogen antagonist-clomiphene-during neonatal life, on later neuroendocrine
      system and reproductive performance. Immediately after birth, male pups received
      clomiphene citrate (s.c.). At adulthood, although testosterone levels and wet
      weights of reproductive organs were not altered, the treatment induced an
      increased number of spermatozoa and a delay in the transit time in the cauda
      epididymis. Additionally, there was impairment of sexual behavior evidenced by a
      delay in the latencies to the first mount and first intromission. Treated rats
      also showed decreased dopaminergic and serotonergic neurotransmissions in the
      hypothalamus and decreased dopaminergic neurotransmission in the striatum. The
      decreased dopaminergic activity could be related to the lower sexual motivation
      observed. These results indicate the necessity of preventing exposure to drugs
      that may impair sexual differentiation, which can compromise later mating success
      as well as the capacity to generate descendants.

PMID- 16650889
TI  - Application of assisted reproduction for population management in felids: the
      potential and reality for conservation of small cats.
AB  - Assisted reproductive technology (ART), using the primary applied tools of AI,
      ET, and sperm and embryo cryopreservation, has been promoted over the past
      decades for its potential to conserve endangered wildlife, including felids.
      However, if the goal is efficient, consistent production of viable offspring for
      population management, then the 'potential' of ART has yet to become 'reality'
      for any non-domestic cat species. For the five small-sized felids (i.e.,
      Brazilian ocelot, fishing cat, Pallas' cat, Arabian sand cat, black-footed cat)
      managed by Species Survival Plans (SSPs) in North American zoos, achieving this
      potential may be an absolute necessity if genetically viable captive populations
      are to be maintained into the next century. Modeling programs suggest that
      current SSP populations are not sustainable without periodic introduction of new
      founders and improved demographic parameters, including longer generation
      intervals and larger population sizes. ART provides the means to address each of
      these management challenges. In each small cat SSP species, fecal hormone
      metabolite assays and seminal analysis have proven useful for characterizing
      basal reproductive parameters, a necessary prerequisite to developing ART. Of the
      five SSP species, ART has been used to produce living offspring only in the
      ocelot, including after AI with frozen-thawed spermatozoa and following transfer
      of frozen-thawed IVF embryos. The true efficacy of these techniques, however, is
      still unknown. To improve the applicability of ART for population management,
      priorities for immediate research include further investigation of ovarian
      stimulation protocols, sperm and embryo cryopreservation methods, embryo culture
      systems, and fetal and neonatal viability following ART.

PMID- 16650890
TI  - Parameters influencing the stealthiness of colloidal drug delivery systems.
AB  - Over the last few decades, colloidal drug delivery systems (CDDS) such as nano
      structures have been developed in order to improve the efficiency and the
      specificity of drug action. Their small size permits them to be injected
      intravenously in order to reach target tissues. However, it is known that they
      can be rapidly removed from blood circulation by the immune system. CDDS are
      removed via the complement system and via the cells of the mononuclear phagocyte
      system (MPS), after their recognition by opsonins and/or receptors present at the
      cell surface. This recognition is dependent on the physicochemical
      characteristics of the CDDS. In this study, we will focus on parameters
      influencing the interactions of opsonins and the macrophage plasma membrane with
      the surface of CDDS, whereby parameters of the polymer coating become necessary
      to provide good protection.

PMID- 16650891
TI  - Injectable and macroporous calcium phosphate cement scaffold.
AB  - Calcium phosphate cement (CPC) can be molded and self-hardens in vivo to form
      resorbable hydroxyapatite with excellent osteoconductivity. The objective of this
      study was to develop an injectable, macroporous and strong CPC, and to
      investigate the effects of porogen and absorbable fibers. Water-soluble mannitol
      was used as porogen and mixed with CPC at mass fractions from 0% to 50%. CPC with
      0-40% mannitol was fully extruded under a syringe force of 10 N. The paste with
      50% mannitol required a 100-N force which extruded only 66% of the paste. At
      fiber volume fraction of 0-5%, the paste was completely extruded. However, at 6%
      and 7.5% fibers, some fibers were left in the syringe after the paste was
      extruded. The injectable CPC scaffold had a flexural strength (mean+/-sd; n=5) of
      (3.2+/-1.0) MPa, which approached the reported strengths for sintered porous
      hydroxyapatite implants and cancellous bone. In summary, the injectability of a
      ceramic scaffold, a macroporous CPC, was studies for the first time. Processing
      parameters were tailored to achieve high injectability, macroporosity, and
      strength. The injectable and strong CPC scaffold may be useful in surgical sites
      that are not freely accessible by open surgery or when using minimally invasive
      techniques.

PMID- 16650892
TI  - Src transduces signaling via growth hormone (GH)-activated GH receptor (GHR)
      tyrosine-phosphorylating GHR and STAT5 in human leukemia cells.
AB  - Most human leukemia cells are shown to express growth hormone receptor (GHR) and
      some of them proliferate in response to GH. We demonstrate that Src contributes
      to GHR-mediated signal transduction via STAT5 activation in F-36P human leukemia
      cells stimulated with GH. The tyrosine phosphorylation levels of GHR and STAT5
      induced by GH decreased in the presence of PP2 Src kinase inhibitor. When GHR and
      wild-type Src were co-expressed in COS7 cells, GHR was markedly tyrosine
      phosphorylated as well as when Jak2 was co-expressed with GHR, but not when
      kinase-inactive Src co-expressed. The treatment of F-36P cells with the antisense
      src oligonucleotides, which selectively decreased the Src expression, reduced the
      rhGH-induced tyrosine phosphorylation of the STAT5 activation sites.

PMID- 16650893
TI  - Chronic lymphocytic leukaemia Is terminal del(14)(q24) a new marker for
      prognostic stratification?
AB  - In a patient with chronic lymphocytic leukemia (CLL) molecular cytogenetics
      showed terminal del(14)(q24). Fluorescence in situ hybridisation (FISH) narrowed
      the deletion to a 35 megabases DNA segment, with the proximal breakpoint between
      two partially overlapping clones, RP1-116J24 and RP5-1119N5. Besides loss of
      material at 14q24-qter, comparative genomic hybridisation (CGH) showed loss of
      3p21.3-pter, 4p11-p15.1, 8p12-pter, 13q12-q14, and 15q11-q15, and gain of 3q25
      qter. Del(13)(q12-14) included the RB-1 gene but not D13S319 and D13S25 loci. The
      patient was refractory to fludarabine and rituximab. Our findings and data from
      other reports suggest del(14)(q24) is indicative of aggressive course and is
      closely associated with del(13)(q14) in CLL.

PMID- 16650894
TI  - Induction of human promyelocytic leukemia HL-60 cell differentiation into
      monocytes by arsenic sulphide: involvement of serine/threonine protein
      phosphatases.
AB  - The clinical efficacy of arsenic sulfide (As(4)S(4)), also known as realgar, in
      the treatment of leukemia in China is prompting people to explore the underlying
      mechanism. We examined the realgar-induced differentiation in human promyelocytic
      leukemia cell line HL-60. Cells exhibited proliferation inhibition when treated
      with 0.10-1.5 microM of realgar, and underwent monocytic differentiation as
      indicated by morphological changes, NBT reduction assay, and cytofluorometric
      analyses of the cell surface antigens, CD11b and CD14. Accompanying the
      differentiation, the activity of serine/threonine protein phosphatase type 1
      (PP1) and type 2A (PP2A) were enhanced, whereas the activity of PP2B remained
      virtually the same compared to the control. When cells were treated with realgar
      in the presence of an inhibitor of PP1 and 2A or an inhibitor of PP2B, the
      differentiation of the cells was partially suppressed as revealed by NBT
      reduction assay and the expression of CD14. Our data demonstrate that realgar
      induces monocytic differentiation in HL-60 cells and that some serine/threonine
      protein phosphatases may be involved in the process.

PMID- 16650895
TI  - Evaluation of heavy metal acute toxicity and bioaccumulation in soil ciliated
      protozoa.
AB  - Laboratory toxicity tests, using ciliated protozoa, are scarce and they have been
      carried out usually with freshwater species. In this study, we have analysed the
      acute cytotoxicity of Cd, Zn and Cu in five different strains of very common soil
      ciliate species (Colpoda steinii, Colpoda inflata and Cyrtolophosis elongata),
      which were isolated from very different soil samples (polluted or not with heavy
      metals). Soil ciliates are quite resistant to heavy metals pollution with regard
      to ciliates from other habitats. The toxicity sequence was Cd>Cu>>Zn. Results
      from Cd+Zn mixtures indicated that Cd cytotoxicity decreases in the presence of
      low or moderate Zn concentrations. A broad heavy metal resistance level diversity
      exists among isolates of colpodid ciliates and it is seen to be a genetic feature
      rather than a habitat dependence. Bioaccumulation is seen to be the main
      mechanism involved in the metal resistance, except for Cu. For the first time in
      ciliates, a fluorescent method has been applied to detect Zn intracellular
      deposits. This methodology might be an useful tool for monitoring heavy metal
      pollution in soils.

PMID- 16650896
TI  - Stimulation of pneumovirus-specific CD8+ T-cells using a non-toxic recombinant
      ricin delivery system.
AB  - Internalisation of the plant toxin ricin occurs by retrograde transport which
      delivers the toxin to the ER where it intersects with the MHC class I system for
      peptide antigen display. Here, we describe the generation of an inactivated, non
      toxic, ricin molecule fused to a peptide which elicits a CD8+ T-cell response in
      mice directed against pneumonia virus of mice, a pneumovirus related to human
      respiratory syncytial virus. The ricin fusion elicited a significant T-cell
      response when delivered by intraperitoneal inoculation in the absence of
      adjuvent. Challenge experiments showed that the T-cell response resulting from
      inoculation with the ricin-peptide fusion molecule delayed the onset of virus
      induced disease.

PMID- 16650897
TI  - Gammadelta T cells recognize tumor cells via CDR3delta region.
AB  - The principles governing gammadelta T cell specificity and diversity remain
      unclear due to lack of detailed structural analysis. To elucidate key structural
      basis of the specificity of gammadelta TCR for tumors, we analyzed the binding
      activities of synthesized TCR Vdelta2 CDR3 peptides derived from tumor
      infiltrating lymphocyte (TIL) s in ovarian epithelial carcinoma (OEC) via
      biospecific interaction analysis approach, enzyme immunoassay and
      immunofluorescence assays. Besides, we used human CDR3delta grafted-Ig to repeat
      major tests. We found that synthesized OEC-derived CDR3delta peptides could bind
      specifically to tumor cell lines and tissues. CDR3delta-graft Ig showed a similar
      binding specificity with CDR3delta peptides, suggesting the determinant role of
      CDR3delta in antigen binding. Moreover, CDR3delta peptide-mediated binding
      specificity was blocked by pre-incubation with same peptide, which decreased the
      cytotoxicity of gammadelta T cells to OEC cells in vitro. Our finding indicates
      that CDR3delta peptide could mimic antigen-binding specificity of gammadelta TCR.
      Our strategy provides a novel, simple and convenient approach to investigate the
      binding activity and function of gammadelta TCR.

PMID- 16650898
TI  - p38 MAP kinase drives the expression of mast cell-derived IL-9 via activation of
      the transcription factor GATA-1.
AB  - Mast cells are able to produce a huge panel of mediators including the Th2-type
      cytokine IL-9, which is considered to be a key mediator for the pathogenesis of
      allergic asthma, but detailed information on the regulation of IL-9 transcription
      in mast cells has been scarce. Herein we provide evidence that the
      erythroid/myeloid transcription factor GATA-1, which is not expressed in Th2
      cells, is a potent activator of IL-9 expression in murine bone marrow-derived
      mast cells (BMMC). Furthermore, in mast cells, but not in Th2 cells, production
      of IL-9 is sensitive to inhibition of p38 MAP kinase. As transactivation mediated
      by GATA-1 is also sensitive to inhibition of p38 MAP kinase, and GATA-1 is a
      target for p38 MAP kinase-mediated phosphorylation in vitro, we conclude that
      both signaling molecules represent a part of a mast cell-specific signaling
      network that regulates the expression of IL-9.

PMID- 16650899
TI  - Electrochemical behavior of ferrocene in ionic liquid media.
AB  - Chemistry and applicability of ionic liquids (IL), - organic salts with low
      melting point - are in the focus of interest today. The ILs with melting point
      below room temperature are expected to be good solvents. Their applicability in
      organic synthetic work, in separation processes as well as in electrochemistry is
      very promising. In the work reported here the voltammetric behavior of ferrocene
      in 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM+ PF6-) ionic liquid has
      been investigated. Conventional size and micro platinum and carbon electrodes
      were employed in CV and in chronoamperometric measurements. Karl Fischer method
      was used for the determination of water content of the solvent. Voltammetric
      measurements without addition of background electrolyte could be carried out in
      (BMIM+ PF6-) ionic liquid. A broad potential window could be used. Concentration
      dependence of the electrochemically determined diffusion coefficient of the
      ferrocene was observed.

PMID- 16650900
TI  - Do essential fatty acids have a role in the treatment of depression?
AB  - BACKGROUND: Complementary and alternative medicine (CAM) therapies are used more
      than conventional therapies by people with self-defined anxiety and depression.
      Preliminary evidence supports a hypothesis that low plasma concentration of
      essential fatty acids is associated with depression. Reported here is the result
      of a systematic review examining the therapeutic efficacy of essential fatty
      acids for depression. METHODS: Data sources included Medline, Psychinfo, AMED
      (Allied and Complementary Medicine), and Cochrane Controlled Trials Register
      databases searched from inception through September 2001. English language
      randomized controlled trials, controlled clinical trials, intervention studies,
      case control studies, reviews, and case reports of humans were selected, without
      limits for demographics or co-morbidities. Two abstractors independently
      evaluated each study, then reconciled findings. When possible, between group
      treatment effect size was noted or calculated. RESULTS: Six articles met
      inclusion criteria: one RCT, two reviews, and three case control trials. A common
      outcome measure among the case control trials allowed for direct comparison of
      effect sizes. CONCLUSIONS: The evidence implies promise of a treatment effect of
      omega-3 fatty acids for depression in adults; although a statement of definitive
      clinical efficacy is premature. Further study of essential fatty acids as
      independent and adjuvant therapy for adult depression is indicated, including
      more sophisticated investigation of dose-response in particular populations.

PMID- 16650901
TI  - Clinical and therapeutic implications of predominant polarity in bipolar
      disorder.
AB  - BACKGROUND: To determine the clinical and therapeutic relevance of longitudinally
      predominant polarity for bipolar disorders long-term outcome. METHOD: Two hundred
      twenty-four patients (n=224) were enrolled for the study in the Bipolar Disorders
      Program of Barcelona, which provides integrated care for difficult-to-treat
      bipolar patients derived from all over Spain, but also provides clinical care to
      all bipolar patients coming from a specific catchment area (Eixample Esquerre) in
      Barcelona. Data collection regarding predominant polarity started on October 1994
      and lasted for the following ten years. Patients were divided according to the
      predominance of depressive or manic/hypomanic episodes. The two groups were
      compared regarding clinical and sociodemographic variables. RESULTS: 135 patients
      (60.3%) were classified as Depressive Polarity, whilst 89 (39.7%) were considered
      as Manic Polarity. Manic Polarity was more prevalent amongst bipolar I patients
      than bipolar II. Depressive Polarity was strongly associated with depressive
      onset of bipolar disorder. Lifetime history of attempted suicide was strongly
      associated with Depressive Polarity, who also had a higher mean number of suicide
      attempts. As for therapeutic issues, acute and maintenance use of atypical
      antipsychotics and conventional neuroleptics were more common amongst Manic
      Polarity whilst antidepressants and lamotrigine use was highly prevalent amongst
      Depressive Polarity. CONCLUSIONS: Prevention of depression is crucial for the
      maintenance treatment of bipolar II patients, whilst prevention of mania and
      depression would be equally important in the case of bipolar I patients.
      Predominant polarity is a valid prognostic parameter with therapeutic
      implications.

PMID- 16650902
TI  - Motoric neurological soft signs and psychopathological symptoms in schizophrenic
      psychoses.
AB  - Motoric neurological soft signs (NSS) were investigated by means of the Brief
      Motor Scale (BMS) in 82 inpatients with DSM-III-R schizophrenic psychoses. To
      address potential fluctuations of psychopathological symptoms and extrapyramidal
      side effects, patients were examined in the subacute state, twice at an interval
      of 14 days on the average. NSS were significantly correlated with severity of
      illness, lower social functioning, and negative symptoms. Modest, but significant
      correlations were found between NSS and extrapyramidal side effects as assessed
      on the Simpson-Angus Scale. Neither the neuroleptic dose prescribed to the
      patient, nor scores for tardive dyskinesia and akathisia were significantly
      correlated with NSS. Moreover, NSS scores did not significantly differ between
      patients receiving clozapine and conventional neuroleptics. Patients in whom
      psychopathological symptoms remained stable or improved over the clinical course
      showed a significant reduction of NSS scores. This finding did not apply to those
      patients in whom psychopathological symptoms deteriorated. Our findings
      demonstrate that NSS in schizophrenic psychoses are relatively independent of
      neuroleptic side effects, but they are associated with the severity and
      persistence of psychopathological symptoms and with poor social functioning.

PMID- 16650903
TI  - Holter analyses in children with adenotonsillar hypertrophy.
AB  - OBJECTIVE: The cardiac complications of adenotonsillar hypertrophy (ATH) have
      been investigated by many scientists by using supplemental diagnostic modalities
      such as echocardiography. But, arrhythmia analysis has not been studied
      adequately in patients with ATH. This study aimed at evaluating the prevalence of
      arrhythmias, heart rate variability (HRV) and heart rate turbulence (HRT)
      analyses by means of 24 h Holter ECG monitoring in pre- and post-operative
      periods in children with ATH. METHODS: Twenty-five children with ATH consisting
      of 12 female and 13 male patients (mean age 66+/-15 months, range 24-108 months)
      included in this study. All children were assessed pre-operatively and at 1 month
      post-operatively with 24-h Holter monitoring and ECG analysis. The prevalence
      analysis of arrhythmias, heart rate variability and heart rate turbulence
      analysis was assessed. These data were compared. RESULTS: Although some ECG and
      holter findings such as sinusal tachycardia, Mobitz type 1 second-degree AV block
      improved after the operation, the prevalence of arrhythmias, HRV and HRT values
      were not changed significantly in post-operative period (p>0.05). CONCLUSION:
      Measurement of HRT and HRV are attractive and easily applicable ways of non
      invasive risk prediction of cardiac complications. But, these parameters have not
      changed significantly in post-operative period. However, ECG and 24-h Holter
      monitoring of electrocardiography may be useful at evaluating the prevalence of
      arrhythmias and determining cardiac complications in pre-operative period.

PMID- 16650904
TI  - Evaluation of a commercial real-time PCR assay for quantitation of Epstein-Barr
      virus DNA in different groups of patients.
AB  - The aim of this study was to evaluate the performance of a molecular assay for
      quantitation of Epstein-Barr virus (EBV) DNA based on real-time PCR, and to
      determine EBV DNA levels in EDTA whole blood samples derived from different
      groups of patients. Following a manual DNA extraction protocol, real-time PCR was
      performed using the LightCycler EBV Quantification Kit, which demonstrated
      sufficient accuracy and linearity. Coefficients of variations were found to be
      between 6 and 42% and 5 and 34%, respectively, for inter-assay and intra-assay
      variations. In clinical specimens, EBV DNA was detected in all patients with
      acute EBV infection (n=34), in one of 25 adults with past EBV infection, in 16
      out of 25 (64%) anti-HIV antibody positive persons, in 10 out of 25 (40%) solid
      organ transplant recipients, and in none of the 23 infants without history of EBV
      infection. When EBV DNA levels in positive specimens were compared between
      different groups, statistically significant differences were not found. The
      LightCycler EBV Quantification Kit was found to be useful for determination of
      EBV DNA levels in EDTA whole blood.

PMID- 16650905
TI  - A rapid quantitative PCR-based assay for testing antiviral agents against human
      adenoviruses demonstrates type specific differences in ribavirin activity.
AB  - Human adenovirus (HAdV) infections are increasingly frequent and potentially
      fatal as a disseminated disease in highly immunocompromised patients. Determining
      the in vitro sensitivity of HAdV to antiviral agents is not an easy task because
      HAdV CPE reduction assays are difficult to interpret and may take more than 1
      week. We developed a phenotypic assay for testing the antiviral activity during
      the first round of replication using HAdV DNA concentration as an objective
      readout within 30 h. After evaluating the assay with cidofovir, we focused on
      determining the antiviral of ribavirin against different HAdV serotypes because
      clinical response of HAdV infections towards ribavirin treatment varied
      considerably. Several HAdV prototypes (1, 2, 5, 11, 31, 34, 48) associated with
      disseminated infections and clinical isolates were tested. Predominating HAdV of
      species C were more sensitive to ribavirin (HAdV-2 and -5: EC(50)<10 microM,
      EC(99) 111 and 104 microM, respectively) than HAdV of other species, for example
      HAdV-31 (EC(50) 56 microM, EC(99)>500 microM). Differential ribavirin sensitivity
      of HAdV types may contribute to the variable outcome of ribavirin therapy. Rapid
      screening of antiviral agents with the rapid qPCR-based assay against a multitude
      of HAdV serotypes may also facilitate development of future antiviral agents.

PMID- 16650906
TI  - Decreased heparin cofactor II activity is associated with impaired endothelial
      function determined by brachial ultrasonography and predicts cardiovascular
      events.
AB  - BACKGROUND: Heparin cofactor II (HCII) could inactivate thrombin after binding to
      dermatan sulfate at injured arterial walls, and has been shown to be a novel and
      independent antiatherosclerotic factor. However, the relation between plasma HCII
      activity and peripheral vascular endothelial function remains unclear. METHODS: A
      total of 199 patients (mean age, 63+/-14 years) were enrolled and followed up for
      a median period of 24 months. Endothelial function was assessed using brachial
      ultrasonography to determine endothelium dependent flow-mediated vasodilation
      (FMD). Cox regression analyses were conducted for the 199 subjects, with
      cardiovascular events being defined as myocardial infarction (MI), percutaneous
      coronary intervention (PCI), coronary artery bypass grafting (CABG), ischemic
      stroke, and peripheral artery revascularization. RESULTS: A total of 31 patients
      (16%) had cardiovascular events. Patients with cardiovascular events had
      significantly lower HCII activity (112+/-34 versus 127+/-34%, p=0.027) and lower
      antithrombin III (ATIII) activity (82+/-12 versus 88+/-13%, p=0.014) than those
      without events. By multivariate analysis, age (p=0.012), hsCRP (p=0.020) and HCII
      activity (p=0.035) were correlated with FMD. Kaplan-Meier analysis was performed
      and showed plasma HCII (p=0.036) and ATIII activities (p=0.005) were predictors
      of cardiovascular events. By Cox regression analysis, plasma HCII activity
      (p=0.026) could be an independent predictor of future cardiovascular events, but
      not ATIII. CONCLUSIONS: The present study demonstrates that plasma HCII activity
      is positively correlated with endothelial vasodilator function. Furthermore,
      plasma HCII activity could be a predictor of future cardiovascular events in
      patients with suspected coronary artery disease, suggesting its role in
      atherosclerosis.

PMID- 16650907
TI  - Intracoronary aqueous oxygen perfusion, performed 24 h after the onset of
      postinfarction reperfusion, experimentally reduces infarct size and improves left
      ventricular function.
AB  - BACKGROUND: Intracoronary aqueous oxygen (AO) hyperoxemic perfusion, initiated
      shortly (15-30 min) after the onset of postinfarction reperfusion, reduces
      infarct size and improves left ventricular function. Whether such therapy
      provides similar benefits when administered many hours after the onset of
      reperfusion is unknown. Accordingly, the hypothesis was tested that AO hyperbaric
      perfusion, performed 24 h after the onset of postinfarction reperfusion, reduces
      infarct size and improves left ventricular ejection fraction (LVEF) in swine.
      METHODS: Following a 1-h balloon occlusion of the left anterior descending
      coronary artery in air-ventilated juvenile domestic swine, reperfusion was
      allowed to proceed without adjunctive therapy overnight in all animals. The
      following day, half of the reanesthetized, air-ventilated swine were randomized
      to treatment with intracoronary AO hyperbaric perfusion for 90 min (n=6, mean
      arterial perfusate PO(2)=899+/-78 mm Hg), while the remainder served as controls
      (n=6). RESULTS: Infarct size by triphenyl tetrazolium chloride was reduced by 48%
      and the [area of necrosis]/[area at risk] ratio was reduced by 44% in the AO
      group compared to the control group (p<0.05). By serial ventriculography, mean
      LVEF improved by 21% during AO perfusion, relative to baseline and control group
      values (p<0.05), with no significant change 1 h after completion of treatment
      (p>0.05). CONCLUSION: AO hyperbaric perfusion, delayed 24 h after the onset of
      postinfarction reperfusion, reduces infarct size and improves LVEF in an
      experimental animal model.

PMID- 16650908
TI  - DNA topoisomerase V: a new fold of mysterious origin.
AB  - Although all other topoisomerases have a broad phylogenetic distribution, DNA
      topoisomerase V, the major component of the ThermoFidelase sequencing kit, is
      presently only known in a single species--the archaeon Methanopyrus kandleri.
      Resolution of the structure of this enzyme by Taneja and co-workers now reveals
      that this atypical topoisomerase has no structural similarity with other
      proteins. So, where did it come from? It is my contention that Topo V, and many
      other orphan proteins, could have a viral origin.

PMID- 16650909
TI  - Divide and conquer: development and cell cycle genes in plant transformation.
AB  - Genetic transformation and regeneration of transgenic plants remains unfeasible
      for the majority of plant species. We propose that inducible expression and/or
      suppression of the genes that control the cell cycle and development, by altering
      chromatin structure and exerting epigenetic control of gene expression, might
      substantially improve competence for transformation and/or regeneration.
      Transformation efficiency was higher in cells with nuclei at the S and G2 phases,
      and manipulating the genes whose activation or silencing promote the G1-S
      transition has increased both transient and stable transformation. Controlling
      the cell cycle directly, using RBR and VIP1, or indirectly, through hormone
      regulation using IPT and ESR1, has improved rates of stable transformation. Other
      target genes that might promote incorporation of DNA and/or pluripotency of cells
      include HP1, CycD3 and CycD1. The availability of large EST databanks, complete
      plant-genome sequences and/or inducible gene expression systems create
      opportunities for testing homologous genes to increase competence of
      transformation and regeneration.

PMID- 16650910
TI  - Pharmacokinetic and pharmacodynamic evaluation of a novel in situ forming
      poly(ethylene glycol)-based hydrogel for the controlled delivery of the
      camptothecins.
AB  - Inadequate drug delivery, due to problems associated with achieving constant
      therapeutic blood levels, has hampered the use of anticancer agents of the
      camptothecin (CPT) class. The objective of the current studies was to develop a
      depot delivery system for the water-soluble analog of CPT, topotecan (TPT). In
      this study, a 2-phase drug depot consisting of TPT-loaded liposomes entrapped in
      a poly(ethylene glycol) hydrogel was designed. Physically entrapped unaltered TPT
      displayed a rapid release rate from the hydrogel. Controlled release was
      demonstrated in vitro and in vivo from the 2-phase system with constant blood
      levels being achieved for several days in rats. Cytotoxicity and antitumor
      activity were also evaluated in rats inoculated with syngeneic MAT B III breast
      cancer cells. Rats treated with the liposome-loaded hydrogel displayed
      significantly longer tumor growth suppression and did not exhibit body weight
      loss compared to those treated with other delivery modes. These experiments
      constitute a proof-of-principle of the 2-phase depot concept and its potential
      value for enhancing safety and efficacy in chemotherapy.

PMID- 16650911
TI  - Role of stent design and coatings on restenosis and thrombosis.
AB  - More than 15 years have passed since stent technology was introduced by Sigwart
      et al. [U. Sigwart, J. Puel, V. Mirkovitch, F. Joffe, et al. Intravascular stents
      to prevent occlusion and restenosis after transluminal angioplasty. N. Engl. J.
      Med. 316 (1987) 701-706.] among interventional cardiologists. Recently drug
      eluting stents have assumed dominance in the interventional world as positive
      trial results revealed their efficacy for preventing restenosis. Stent design,
      delivery-vehicle materials, and drug properties affect the function of these
      stents. Stainless steel stents with tubular and multicellular design have proven
      superior to coil or hybrid stent models. This chapter describes stents which have
      subtle influences of modular design, metal coverage, strut thickness, strut
      shape, surface smoothness, and coating materials like an alloy composition.

PMID- 16650912
TI  - Exogenous proline mitigates the detrimental effects of salt stress more than
      exogenous betaine by increasing antioxidant enzyme activities.
AB  - Proline and betaine accumulate in plant cells under environmental stresses
      including salt stress. Here, we investigated effects of proline and betaine on
      the growth and activities of antioxidant enzymes in tobacco Bright Yellow-2 (BY
      2) culture cells in suspension under salt stress. Both proline and betaine
      mitigated the inhibition of growth of BY-2 cells under salt stress and the
      mitigating effect of proline was more than that of betaine. Salt stress
      significantly decreased the activities of superoxide dismutase (SOD), catalase
      and peroxidase in BY-2 cells. Exogenous application of proline or betaine
      alleviated the reduction in catalase and peroxidase activities but not SOD
      activity under salt stress. In addition, proline was found to be effective in
      alleviating the inhibition of salt stress-induced catalase and peroxidase
      activities in BY-2 cells. Neither proline nor betaine directly scavenged
      superoxide (O(2)(-)) or hydrogen peroxide (H(2)O(2)). It is concluded that
      exogenous proline mitigates the detrimental effects of salt stress more than
      exogenous betaine because of its superior ability to increase the activities of
      antioxidant enzymes.

PMID- 16650913
TI  - Multiple types of dieting prospectively predict weight gain during the freshman
      year of college.
AB  - The freshman year of college is a period of heightened risk for weight gain. This
      study examined measures of restrained eating, disinhibition, and emotional eating
      as predictors of weight gain during the freshman year. Using Lowe's multi
      factorial model of dieting, it also examined three different types of dieting as
      predictors of weight gain. Sixty-nine females were assessed at three points
      during the school year. Weight gain during the freshman year averaged 2.1 kg.
      None of the traditional self-report measures of restraint, disinhibition, or
      emotional eating were predictive of weight gain. However, both a history of
      weight loss dieting and weight suppression (discrepancy between highest weight
      ever and current weight) predicted greater weight gain, and these effects
      appeared to be largely independent of one another. Individuals who said they were
      currently dieting to lose weight gained twice as much (5.0 kg) as former dieters
      (2.5 kg) and three times as much as never dieters (1.6 kg), but the import of
      this finding was unclear because there was only a small number of current dieters
      (N = 7). Overall the results indicate that specific subtypes of dieting predicts
      weight gain during the freshman year better than more global measures of
      restraint or overeating.

PMID- 16650914
TI  - Different capacities of various NMDA receptor antagonists to prevent ischemia
      induced neurodegeneration in human cultured NT2 neurons.
AB  - In the present study, human NT2 neurons obtained from embryonic teratocarcinoma
      (NT2) cells were established as human in-vitro model to investigate the
      mechanisms associated with hypoxia/ischemia-induced neuronal injury. NT2 neurons
      express functional NMDA receptors that are of particular significance for
      hypoxia/ischemia-related neuronal damage. In patch-clamp recordings under
      normoxic conditions, NMDA (plus 10 microM glycine)-induced inward currents
      (EC(50)=43.7 microM) were distinctly antagonized by memantine, a blocker of the
      receptor channel, but only slightly by 5,7-dichlorokynurenic acid (DCKA), a
      glycine(B) binding site antagonist. Immunohistochemistry demonstrated that the
      NT2 neurons are mostly GABAergic; they predominantly express the NMDA receptor
      subunits NR2B and NR2C, and lower levels of NR1 and, particularly, of NR2A. Upon
      glucose and oxygen deprivation for 3h the loss of cell viability measured
      directly after 3h was higher than after application of either hypoxia or
      aglycemia as assessed by propidium iodide flow cytometry. Ischemic conditions
      significantly reduced the NMDA responses associated with a decrease in EC(50) and
      decreased mitochondrial membrane potential as detected by JC-1 flow cytometry.
      Memantine (50 microM) and CGS19755 (a competitive NMDA receptor antagonist; 10
      microM) reduced ischemia-induced cell death, in contrast to DCKA (10 microM). In
      conclusion, in the present human in-vitro model for studying the molecular
      mechanisms associated with ischemic injury, neuroprotection could be achieved
      with NMDA receptor antagonists but not with a glycine(B) binding site antagonist.
      Accordingly, glycine antagonists might not represent an optimal therapeutic
      strategy for preventing ischemic neuronal damage in contrast to NMDA receptor
      antagonists like memantine.

PMID- 16650915
TI  - DNA vaccination can protect Cyprinus Carpio against spring viraemia of carp
      virus.
AB  - Several DNA constructs containing the spring viraemia of carp virus (SVCV)
      glycoprotein (G) gene were investigated for their ability to induce protection
      against SVCV following injection into myofibres. The constructs were pooled into
      four groups and co-injected with a plasmid encoding murine granulocyte-macrophage
      colony-stimulating factor. Group 1 contained one full-length and two truncated G
      constructs under the control of the cytomegalovirus (CMV) promoter. Group 2
      contained full-length constructs with the CMV promoter, the simian virus 40
      promoter and a muscle-specific promoter. Group 3 contained constructs in which
      the G-gene was fused with a second gene in order to improve secretion of the G
      protein or to enhance destruction of transfected myocytes by T cells. Group 4
      contained constructs with the CMV-Intron A promoter in plasmids with or without
      CpG motifs. A small-scale trial in goldfish showed that antibody responses in at
      least half the fish were induced by three injections of plasmids from Groups 1
      and 3 whereas T-cell like responses with stimulation indices of above 3 were
      induced in at least half the fish by Groups 2 and 4. A single-dose of each
      plasmid mix was then used to protect carp in a large-scale trial. Following
      challenge with a heterologous strain of SVCV that killed 64% of fish, the
      strongest protection was observed in carp that received the full length G-gene
      expressed by two plasmids driven by the CMV-Intron A promoter (Group 4), with a
      relative percentage survival of 48% (p=0.00008).

PMID- 16650916
TI  - Factors influencing MMR vaccination decisions following a mumps outbreak on a
      university campus.
AB  - Following a number of mumps outbreaks in universities and colleges, the UK Health
      Protection Agency has suggested that it is appropriate to consider offering the
      MMR vaccine in these settings. However, little is known about the factors
      associated with uptake of the MMR jab or perceptions of risks/benefits of the
      vaccine among higher education students. The current study focused on a sample of
      students offered the MMR vaccine following an outbreak of mumps on a university
      campus. Perceptions of risks/benefits of the vaccine varied considerably and
      students were unlikely to have the jab when perceived risks of immunising were
      equivalent to perceived risks of not immunising. Results suggest that public
      health interventions should address students' attitudes towards the vaccine,
      perceptions of peer expectations, and perceptions of barriers to uptake.

PMID- 16650917
TI  - Induction of protective and mucosal immunity against diphtheria by a immune
      stimulating complex (ISCOMS) based vaccine.
AB  - There is increasing concern over the efficacy of existing vaccines for diphtheria
      and there is interest in the development of a mucosally active formulation which
      might improve local protection. Lipophilic immune stimulating complexes (ISCOMS)
      containing Quil A are active by both parenteral and mucosal routes and here we
      have established methods for incorporating palmitified diphtheria toxoid (DT)
      into ISCOMS. The resulting formulation was immunogenic by the subcutaneous, oral
      and intranasal routes, with very low doses of DT inducing systemic humoral immune
      responses, as well as cell mediated immunity including both gammaIFN and IL5
      production. Intranasal immunisation with DT in ISCOMS also stimulated significant
      local antibody production in tracheal washes, as well as cellular immunity in
      draining lymphoid tissues and serum neutralising antibodies. Finally,
      subcutaneous immunisation of guinea pigs with DT in ISCOMS primed protective
      immunity against challenge with diphtheria holotoxin more efficiently than the
      equivalent doses of DT in the conventional alum vaccine. ISCOMS based vaccines
      may provide a novel strategy for mucosal and systemic immunisation against
      diphtheria.

PMID- 16650918
TI  - Long-term reduction in (137)Cs concentration in food crops on coral atolls
      resulting from potassium treatment.
AB  - Bikini Island was contaminated on March 1, 1954 by the Bravo detonation (U.S.
      nuclear test series, Castle) at Bikini Atoll. About 90% of the estimated dose
      from nuclear fallout to potential island residents is from cesium-137 ((137)Cs)
      transferred from soil to plants that are consumed by residents. Thus,
      radioecology research efforts have been focused on removing (137)Cs from soil
      and/or reducing its uptake into vegetation. Most effective was addition of
      potassium (K) to soil that reduces (137)Cs concentration in fruits to 3-5% of
      pretreatment concentrations. Initial observations indicated this low
      concentration continued for some time after K was last applied. Long-term studies
      were designed to evaluate this persistence in more detail because it is very
      important to provide assurance to returning populations that (137)Cs
      concentrations in food (and, therefore, radiation dose) will remain low for
      extended periods, even if K is not applied annually or biennially. Potassium
      applied at 300, 660, 1260, and 2070 kg ha(-1) lead to a (137)Cs concentration in
      drinking-coconut meat that is 34, 22, 10, and about 4% of original concentration,
      respectively. Concentration of (137)Cs remains low 8-10 y after K is last
      applied. An explanation for this unexpected result is discussed.

PMID- 16650919
TI  - Isotopic signature of atmospheric xenon released from light water reactors.
AB  - A global monitoring system for atmospheric xenon radioactivity is being
      established as part of the International Monitoring System to verify compliance
      with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The isotopic activity
      ratios of (135)Xe, (133m)Xe, (133)Xe and (131m)Xe are of interest for
      distinguishing nuclear explosion sources from civilian releases. Simulations of
      light water reactor (LWR) fuel burn-up through three operational reactor power
      cycles are conducted to explore the possible xenon isotopic signature of nuclear
      reactor releases under different operational conditions. It is studied how ratio
      changes are related to various parameters including the neutron flux, uranium
      enrichment and fuel burn-up. Further, the impact of diffusion and mixing on the
      isotopic activity ratio variability are explored. The simulations are validated
      with reported reactor emissions. In addition, activity ratios are calculated for
      xenon isotopes released from nuclear explosions and these are compared to the
      reactor ratios in order to determine whether the discrimination of explosion
      releases from reactor effluents is possible based on isotopic activity ratios.

PMID- 16650920
TI  - Probabilistic biokinetic modelling of radiocaesium uptake in Arctic seal species:
      verification of modelled data with empirical observations.
AB  - The necessity to provide information about radionuclide concentrations in Arctic
      marine species has been heightened in recent years due to a number of accidents
      in Arctic regions involving nuclear vessels and the presence of a large number of
      potential radioactive contamination sources. The provision for such information
      is largely dependent on the use of radionuclide uptake and transfer models. The
      uptake of radionuclides in Arctic seal species in this study has been modelled
      using a probabilistic biokinetic approach. In this paper, model results are
      compared with empirical data from relevant samples taken within the Arctic
      region. Results indicate that the model performs well when estimating
      concentrations of (137)Cs in two seal species for both median values and
      reproduction of the distribution of data values, but not as well for a third seal
      species. Likely factors affecting the results are the probability density
      functions used for the input parameters.

PMID- 16650921
TI  - Socioeconomic inequalities in health: a comparative longitudinal analysis using
      the European Community Household Panel.
AB  - This study measures socioeconomic inequalities in health across European Union
      Member States between 1994 and 2001. The analysis is based on the European
      Community Household Panel Users' Database (ECHP-UDB) and uses two binary
      indicators of health limitations for the full 8 waves of available data. Short-
      and long-run concentration indices together with mobility and health achievement
      indices are derived for indicators of severe health limitation and any health
      limitation. Results demonstrate the existence of socioeconomic inequality in
      health across Member States in both the short-term (1 year) and the long-term (up
      to 8 years), with health limitations concentrated among those with lower incomes.
      For all countries, the long-run indices show that income-related inequalities in
      health widen over time, in the sense that the longer the period over which an
      individual's health and income are measured the greater the measure of income
      related health inequality. The ranking of countries according to their prevalence
      of illness differs from ranking by overall health achievement, which takes
      account of inequalities. This means that an equity-efficiency trade-off has to be
      faced in evaluating the performance of different countries and in comparing
      countries with diverse health and social welfare systems.

PMID- 16650922
TI  - Operative laparoscopy in The Netherlands: Diffusion and acceptance.
AB  - OBJECTIVE: To evaluate and update the current status of the implementation of
      operative laparoscopy in gynaecology in The Netherlands by assessing diffusion
      and acceptance of each specific procedure per hospital. STUDY DESIGN: In 2003 a
      questionnaire was sent to all hospitals (n = 102), which addressed the total
      number and type of laparoscopic procedures performed in 2002 stratified by level
      of difficulty (level 1: diagnostic laparoscopy, sterilization, tubal patency
      tests; level 2: adhesiolysis, ectopic pregnancy (EP), laparoscopic treatment of
      endometriosis, cystectomy, oophorectomy, LAVH, tubal surgery for infertility;
      level 3: myomectomy, total laparoscopic hysterectomy (TLH) and sacropexy). Data
      were compared to previously published data of 1994. RESULTS: Response rate was
      79% (81/102). Diffusion and acceptance of level 2 procedures increased
      significantly, except endometriosis and tubal surgery for infertility. Diffusion
      of LAVH was only 58%. Four percent of hysterectomies were LAVH. TLH and sacropexy
      were not performed. The diffusion of myomectomy increased significantly (p =
      0.01), whereas its acceptance remained low. CONCLUSIONS: Although the diffusion
      of operative procedures has increased over the last decade, acceptance is still
      limited, especially for laparoscopic hysterectomy. The implementation of
      operative gynaecological laparoscopy in The Netherlands seems to develop at a
      slow pace.

PMID- 16650923
TI  - The "interceptor" properties of chlorophyllin measured within the three-component
      system: intercalator-DNA-chlorophyllin.
AB  - In aqueous solutions, in the presence of double-stranded DNA, chlorophyllin (CHL)
      forms complexes with each of the three DNA intercalators: acridine orange (AO),
      quinacrine mustard (QM), and doxorubicin (DOX). The evidence for these
      interactions was obtained by measurement changes in the absorption and
      fluorescence spectra of the mixtures containing DNA and intercalators during
      titration with CHL. A model of simple competition between DNA and CHL for the
      intercalator was used to define the measured interactions. The concentrations of
      the complexes estimated based on this model were consistent with the
      concentrations obtained by actual measurement of the absorption spectra. The
      present data provide further support for the role of chlorophyllin as an
      "interceptor" that may neutralize biological activity of aromatic compounds
      including mutagens and antitumor drugs.

PMID- 16650924
TI  - Watching the face of Janus--active surveillance as a strategy to reduce
      overtreatment for localised prostate cancer.

PMID- 16650925
TI  - Women's sexual dysfunction: a review of the "surgical landscape".
AB  - OBJECTIVES: To assess the impact of urogynaecologic surgery for stress urinary
      incontinence, oncologic pelvic surgery, and hysterectomy on women's overall
      sexual health. METHODS: We used Ovid and PubMed (updated January 2006) to conduct
      a literature electronic search on MEDLINE that included peer-reviewed English
      language articles. We analysed all studies identified that provided any
      functional outcome data about urogynaecologic surgery for the treatment of stress
      urinary incontinence, radical cystectomy for bladder cancer, surgery for rectal
      cancer, and hysterectomy. Because of the substantial heterogeneity of outcome
      measures and follow-up intervals in case studies, we did not apply meta-analytic
      techniques to the data. RESULTS: Most studies showed that either urogynaecologic
      or oncologic pelvic surgery may have a significant impact on women's sexual
      health. Epidemiology varied widely among the studies and reported either
      improvement or impairment of postoperative sexual functioning, due to different
      definitions, study designs, and small cohorts of patients. An increasing number
      of studies have prospectively examined this issue and have found often
      controversial findings about the role of pelvic and perineal surgery in women's
      sexual health. CONCLUSIONS: Although numerous controversies exist, data
      demonstrate an overall positive impact of the surgical repair for stress urinary
      incontinence on resolution of coital incontinence, coupled with an improvement of
      overall sexual life. In contrast, genitourinary and rectal cancers are commonly
      associated with treatment-related sexual dysfunction, but few studies rigorously
      assessed women's postoperative sexual function after major oncologic pelvic
      surgery. Data about the functional outcome after hysterectomy are often
      contradictory. Adequately powered prospective clinical trials are needed.

PMID- 16650927
TI  - Neural membrane microdomains as computational systems: Toward molecular modeling
      in the study of neural disease.
AB  - Several studies indicate that the lipid biological membrane contains discrete
      regions known as rafts or microdomains. These structures range in size from
      approximately 50 to 70nm to nearly a mum and play important roles in cell
      signaling. In the neuron, computational models suggest that transiently polarized
      microdomain ethenes may regulate ion-channel dynamics and control impulse
      propagation. Thus the microdomain is nominated as the fundamental unit of nervous
      system signaling. Based on this model, the article proposes a first-approximation
      design for a supported-membrane device which would mimic microdomain properties.
      The basic architecture would consist of an electrically addressable biotemplated
      nanowire crossing an artificial membrane corralled in a vertical carbon nanofiber
      barrier. Advantages and disadvantages of model components are discussed at
      length. It is proposed that artificial devices of this type would be medically
      useful in simulating membrane states correlated with neural disease. This
      possibility is examined with reference to the A-current potassium channel,
      implicated in epilepsy.

PMID- 16650928
TI  - Network topology and the evolution of dynamics in an artificial genetic
      regulatory network model created by whole genome duplication and divergence.
AB  - Topological measures of large-scale complex networks are applied to a specific
      artificial regulatory network model created through a whole genome duplication
      and divergence mechanism. This class of networks share topological features with
      natural transcriptional regulatory networks. Specifically, these networks display
      scale-free and small-world topology and possess subgraph distributions similar to
      those of natural networks. Thus, the topologies inherent in natural networks may
      be in part due to their method of creation rather than being exclusively shaped
      by subsequent evolution under selection. The evolvability of the dynamics of
      these networks is also examined by evolving networks in simulation to obtain
      three simple types of output dynamics. The networks obtained from this process
      show a wide variety of topologies and numbers of genes indicating that it is
      relatively easy to evolve these classes of dynamics in this model.

PMID- 16650929
TI  - Experimental percolation under intermittent conditions: influence on pollutants
      emission from waste.
AB  - As a precautionary measure, the re-use (or landfill) of waste requires an
      environmental assessment of its potential impact. This assessment is usually made
      by simulating the emission of pollutants with a predictive model based on
      laboratory tests (standardised batch leaching tests, up-flow percolation tests,
      acid neutralisation capacity tests [CEN, Characterisation of Waste--Leaching-
      Compliance Test for Leaching of Granular Waste Materials and Sludges, European
      Committee for Standardisation (ECS), Brussels, 2002 ; CEN, prCEN/TS 14405
      Characterisation of Waste--Leaching Behaviour Tests--Up-flow Percolation Test
      (under specified conditions), ECS, Brussels, 2002 ; CEN, prCEN/TS 14429
      Characterisation of Waste--Leaching Behaviour Test--Influence of pH on Leaching
      with Initial Acid/base Addition, ECS, Brussels, 2003 ]. These tests are performed
      with simpler conditions than those occurring in the scenario of re-use (saturated
      media, permanent inflow ...). In order to evaluate the relevance of these tests
      to be considered as a reference for predictive model, the purpose of this work is
      to determine how the intermittent hydrodynamic flow influences the pollutants
      release of unsaturated waste. As a result, we could estimate whether this
      parameter should be introduced in the model.

PMID- 16650930
TI  - Ozonation of benzothiazole saturated-activated carbons: influence of carbon
      chemical surface properties.
AB  - The combined or sequential use of ozone and activated carbon to treat toxic
      effluents has increased in recent years. However, little is known about the
      influence of carbon surface active sites on ozonation of organic adsorbed
      pollutants. This paper presents experimental results on the effect of metal
      oxides and oxygenated surface groups on gaseous ozonation of spent activated
      carbons. Benzothiazole (BT) was selected as a target organic compound in this
      study due to its environmental concern. Activated carbons with different chemical
      surface composition were prepared from a Filtrasorb-400 activated carbon. Pre
      treatment included: ozonation, demineralisation, and deoxygenation of activated
      carbon. Ozonation experiments of BT saturated-activated carbons were conducted in
      a fixed bed reactor loaded with 2 g of carbon samples. The reactor was fed with
      an O2/O3 gas mixture (2 dm3/min, 5 g O3/h), for a given exposure time, in the
      range 10-120 min, at 298 K and 1 atm. Results show that extended gaseous
      ozonation of activated carbon saturated with BT led to the effective destruction
      of the adsorbate by oxidation reactions. Oxidation of BT adsorbed on activated
      carbon seemed to occur via both direct reaction with ozone molecules, and by
      oxygen radical species generated by catalytic ozone decomposition on metallic
      surface sites.

PMID- 16650931
TI  - Changes in phase space during learning an unstable balance.
AB  - Six participants learned to maintain an unstable balance on a stabilometer,
      during 6 consecutive days of practice (total of 90 trials). Lateral and angular
      variations of body segments and body center of mass were analysed, and their
      evolution over the learning period was compared to the changes in dimensional
      variables capturing the structure of the movement itself (embedding and
      correlation dimension, largest Lyapunov exponent). Results indicated that (i)
      learning occurred, (ii) was accompanied by persistence in the dimension of the
      movement, and (iii) by a reduction in chaotic (or stochastic) components.
      Compared to other results in the learning literature, these results suggest that
      dimensional changes over learning are task-specific.

PMID- 16650932
TI  - Nanotribological and nanomechanical characterization of human hair using a
      nanoscratch technique.
AB  - Human hair ( approximately 50-100 microm in diameter) is a nanocomposite
      biological fiber with well-characterized microstructures, and is of great
      interest for both cosmetic science and materials science. Characterization of
      nanotribological and nanomechanical properties of human hair including the
      coefficient of friction and scratch resistance is essential to develop better
      shampoo and conditioner products and advance biological and cosmetic science. In
      this paper, the coefficient of friction and scratch resistance of Caucasian and
      Asian hair at virgin, chemo-mechanically damaged, and conditioner-treated
      conditions are measured using a nanoscratch technique with a Nano Indenter II
      system. The scratch tests were performed on both the single cuticle cell and
      multiple cuticle cells of each hair sample, and the scratch wear tracks were
      studied using scanning electron microscopy (SEM) after the scratch tests. The
      effect of soaking on the coefficient of friction, scratch resistance, hardness
      and Young's modulus of hair surface were also studied by performing experiments
      on hair samples which had been soaked in de-ionized water for 5 min. The
      nanotribological and nanomechanical properties of human hair as a function of
      hair structure (hair of different ethnicity), damage, treatment and soaking are
      discussed.

PMID- 16650933
TI  - Observation of self-assembled fluorescent beads by scanning near-field optical
      microscopy and atomic force microscopy.
AB  - Optical response and topography of fluorescent latex beads both on flat self
      assembled monolayer and on a micron-patterned surface with poly(dimethylsiloxane)
      are studied. Scanning near-field optical microscopy and atomic force microscopy
      were utilized together for detecting fluorescence and imaging topography of the
      patterned latex beads, respectively. As a result, the micro-patterned latex beads
      where a specific chemical binding occurred show a strong signal, whereas no
      signals are observed in the case of nonspecific binding. With fluorescein
      isothiocyanate (FITC), it is convenient to measure fluorescence signal from the
      patterned beads allowing us to monitor the small balls of fluorescent latex.

PMID- 16650934
TI  - Effective mass and flow patterns of fluids surrounding microcantilevers.
AB  - An analytical approach to determine the streamlines of fluid flow adjacent to the
      surfaces of vibrating cantilevers is presented. Fluid flow over the top and
      bottom surfaces of a microcantilever is established by solving two-dimensional
      Navier-Stokes equations for viscous flow. The x and y velocity components are
      used to establish streamlines for absolute fluid motion. These streamlines show a
      central stagnation core perpendicular and central to the cantilever surface
      extending along the full length of cantilevers, which most likely accounts for
      the added mass effect (induced mass) of fluid media around vibrating
      microcantilevers.

PMID- 16650935
TI  - Studying silane mobility on hydrated mica using ambient AFM.
AB  - The mobility of the mono-functional aminosilane, aminopropyldimethylmethoxysilane
      (APDMMS), on mica has been investigated under ambient relative humidity (RH)
      using tapping-mode (TM) AFM. Silane layers were formed from vapour phase at
      various, controlled humidities and then imaged at ambient laboratory conditions
      (typically 30-40% RH). At low RH of formation (<25%) films without any resolvable
      sub-structure were formed, and these were stable to the imaging probe. At high RH
      of formation (>25%), where islands of phase II water are known to exist on mica,
      a two-phase domain structure was seen as two height levels and the surface area
      of the higher domains correlated with the RH. Sequential images taken over a 30
      60 min time period show that these domains are mobile and at intermediate to high
      RH the domains coalesce under the influence of the scanning AFM tip. The results
      suggest the APDMMS resides at the air-water interface (rather than interacting
      with the mica) and that it preferentially interacts with the mobile phase II
      water as opposed to the phase I water tightly bound to the mica.

PMID- 16650936
TI  - Canine intestinal helminths in Finland: prevalence, risk factors and endoparasite
      control practices.
AB  - In this survey, the prevalence of canine gastrointestinal helminths in Finland
      was investigated by coprological examination (n = 541) and possible risk factors
      for helminth infections in dogs were analysed. In addition, the dog owners (n =
      296) completed a questionnaire about use of anthelmintics, sources of information
      about parasites and antiparasitic treatments and reasons for choosing the drugs.
      The prevalence of gastrointestinal helminths was 5.9%. Eggs from four different
      species were identified in the faecal samples. Toxocara canis eggs were present
      in 17 dogs (3.1%), Uncinaria stenocephala eggs in 14 dogs (2.6%) and
      Diphyllobothrium latum eggs in 2 dogs (0.4%). Moreover, one sample contained eggs
      of Trichuris vulpis (0.2%). Kennel housing and visits abroad were identified as
      risk factors for T. canis and U. stenocephala infections. Most dogs (86.0%)
      received anthelmintic treatment at least once a year. Hunting dogs were dewormed
      least; one-third was treated less than once a year. Approximately, half of the
      owners occasionally changed the anthelmintic used. The most important trait of
      the anthelmintic was its broad spectrum, fenbendazole being the most commonly
      chosen. Veterinarians, dog magazines and dog breeders were the predominant
      sources of information concerning parasites and deworming strategies.

PMID- 16650937
TI  - Tryptophan environment, secondary structure and thermal unfolding of the
      galactose-specific seed lectin from Dolichos lablab: fluorescence and circular
      dichroism spectroscopic studies.
AB  - Fluorescence and circular dichroism spectroscopic studies were carried out on the
      galactose-specific lectin from Dolichos lablab seeds (DLL-II). The
      microenvironment of the tryptophan residues in the lectin under native and
      denaturing conditions were investigated by quenching of the intrinsic
      fluorescence of the protein by a neutral quencher (acrylamide), an anionic
      quencher (iodide ion) and a cationic quencher (cesium ion). The results obtained
      indicate that the tryptophan residues of DLL-II are largely buried in the
      hydrophobic core of the protein matrix, with positively charged side chains
      residing close to at least some of the tryptophan residues under the experimental
      conditions. Analysis of the far UV CD spectrum of DLL-II revealed that the
      secondary structure of the lectin consists of 57% alpha-helix, 21% beta-sheet, 7%
      beta-turns and 15% unordered structures. Carbohydrate binding did not
      significantly alter the secondary and tertiary structures of the lectin. Thermal
      unfolding of DLL-II, investigated by monitoring CD signals, showed a sharp
      transition around 75 degrees C both in the far UV region (205 nm) and the near UV
      region (289 nm), which shifted to ca. 77-78 degrees C in the presence of 0.1 M
      methyl-beta-D-galactopyranoside, indicating that ligand binding leads to a
      moderate stabilization of the lectin structure.

PMID- 16650938
TI  - Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates
      neuronal damage and astrogliosis after focal cerebral ischemia in rats.
AB  - Cysteinyl leukotrienes are potent pro-inflammatory mediators. Cysteinyl
      leukotriene receptor 1 is one of the two cysteinyl leukotriene receptors cloned.
      We recently reported that cysteinyl leukotriene receptor 1 antagonists protected
      against cerebral ischemic injury, and an inducible expression of cysteinyl
      leukotriene receptor 1 was found in neuron- and glial-appearing cells after
      traumatic injury in human brain. To determine the role of cysteinyl leukotriene
      receptor 1 in ischemic brain injury, we investigated the temporal and spatial
      profile of cysteinyl leukotriene receptor 1 expression in rat brain from 3 h to
      14 days after 30 min of middle cerebral artery occlusion, and observed the effect
      of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, on the ischemic
      injury. We found that cysteinyl leukotriene receptor 1 mRNA expression was up
      regulated in the ischemic core both 3-12 h and 7-14 days, and in the boundary
      zone 7-14 days after reperfusion. In the ischemic core, cysteinyl leukotriene
      receptor 1 was primarily localized in neurons 24 h, and in macrophage/microglia
      14 days after reperfusion; while in the boundary zone it was localized in
      proliferated astrocytes 14 days after reperfusion. Pranlukast attenuated
      neurological deficits, reduced infarct volume and ameliorated neuron loss in the
      ischemic core 24 h after reperfusion; it reduced infarct volume, ameliorated
      neuron loss and inhibited astrocyte proliferation in the boundary zone 14 days
      after reperfusion. Thus, we conclude that cysteinyl leukotriene receptor 1
      mediates acute neuronal damage and subacute/chronic astrogliosis after focal
      cerebral ischemia.

PMID- 16650939
TI  - Does the development of the perigeniculate nucleus support the notion of a
      hierarchical progression within the visual pathway?
AB  - The development of the visual pathway has been extensively studied. However,
      despite of the importance of the perigeniculate nucleus within this pathway,
      there is a lack of information concerning its development. The present study
      examined the dendritic development of perigeniculate nucleus cells using single
      cell injections in 400-500 microm thick fixed brain slices from kittens of
      different ages between postnatal day 0 and postnatal day 125. A total of 189
      perigeniculate nucleus cells were reconstructed from serial sections for
      qualitative and quantitative analysis. Cells during the first month were
      characterized by an abundance of branch points and appendages. There was a
      significant (P>0.05), albeit variable, increase in the number of branch points
      and appendages up to about postnatal day 12 after which the numbers were rapidly
      reduced over the next two weeks. Similarly, appendage numbers significantly
      increased over the first two weeks until postnatal day 17 and then fell to near
      adult levels by postnatal day 34. The majority of branch points and appendages
      occur within 100-200 microm of the soma (10-30% of the dendritic diameter). The
      data indicate that perigeniculate nucleus dendritic maturation lags shortly
      behind that of the retina but may precede that of its dorsal thalamic target, the
      lateral geniculate nucleus. Thus, it may be that the earlier maturation of the
      perigeniculate nucleus and its inhibitory input is a necessary requirement for
      the proper development of retinogeniculate and corticothalamic topographic maps
      within the dorsal lateral geniculate nucleus and perigeniculate nucleus.

PMID- 16650940
TI  - The dreaming sleep stage: a new neurobiological model of schizophrenia?
AB  - The rapid eye movement dreaming sleep stage and schizophrenia are both
      characterized by common intracerebral disconnections, disturbed responsiveness
      and sensory deafferentation processes. Moreover, in both states, there is
      dorsolateral prefrontal deactivation as shown by the decrease of blood flow.
      Finally, identical pharmacological and neurochemical variations are observed for
      acetylcholine, dopamine, noradrenaline, serotonin and glutamate concentrations.
      Consequently, rapid eye movement sleep could become a useful new neurobiological
      model of this mental disease since more functional than current rat models using
      stimulation, lesion or drugs.

PMID- 16650941
TI  - In vivo, competitive blockade of N-methyl-D-aspartate receptors induces rapid
      changes in filamentous actin and drebrin A distributions within dendritic spines
      of adult rat cortex.
AB  - In vitro studies have demonstrated that prolonged N-methyl-D-aspartate receptor
      (NMDAR) blockade triggers a homeostatic up-regulation of NMDARs at synapses. Such
      upregulation can also be seen within 30 min in vivo in adult rats, implicating
      trafficking of reserve pools of NMDARs. Here, we evaluated the involvement of
      filamentous actin (F-actin), the major cytoskeletal component in spines, in this
      rapid in vivo homeostatic response, using biotinylated phalloidin as its probe.
      We also immuno-labeled spines for drebrin A, an F-actin-binding protein found at
      excitatory synapses and with a proposed role of modulating F-actin's cross
      linking with one another and interactions with NMDARs. Quantitative 2-D analysis
      of ultrastructural images revealed that NMDAR blockade increased filamentous
      actin labeling per spine by 62.5% (P<0.005). The proportion of dendritic spines
      immuno-labeled for drebrin A also increased significantly, from 67.5% to 85%
      following NMDAR blockade (P<0.001), especially among larger spines. The frequency
      distributions of spine widths and postsynaptic density lengths were not affected
      by the D-(+)-2-amino-5-phosphonopentanoic acid (D-APV) treatment. However, the
      average postsynaptic density length was reduced by 25 nm among the fewer, drebrin
      A immuno-negative spines, indicating that drebrin A confers stability to synapse
      size. We propose that, in a homeostatic in vivo response, increases of drebrin A
      and F-actin within spines can enhance NMDAR trafficking by reducing cytoskeletal
      rigidity within the spine cytoplasm without changing the overt morphology of axo
      spinous synapses. Alternatively or in addition, the cytoskeletal redistribution
      within spine cytoplasm may be triggered by the D-APV-induced, homeostatic up
      regulation of NMDAR.

PMID- 16650942
TI  - Neural-immune interface in the rat area postrema.
AB  - The area postrema functions as one interface between the immune system and the
      brain. Immune cells within the area postrema express immunoreactivity for the pro
      inflammatory cytokine, interleukin-1beta following challenge with immune
      stimulants, including lipopolysaccharide (from bacterial cell walls). As a
      circumventricular organ, the area postrema accesses circulating immune-derived
      mediators, but also receives direct primary viscerosensory signals via the vagus
      nerve. Neurons in the area postrema contribute to central autonomic network
      neurocircuitry implicated in brain-mediated host defense responses. These
      experiments were directed toward clarifying relationships between immune cells
      and neurons in the area postrema, with a view toward potential mechanisms by
      which they may communicate. We used antisera directed toward markers indicating
      microglia (CR3/CD11b; OX-42), resident macrophages (CD163; ED-2), or dendritic
      cell-like phenotypes (major histocompability complex class II; OX-6), in area
      postrema sections from lipopolysaccharide-treated rats processed for light, laser
      scanning confocal, and electron microscopy. Lipopolysaccharide treatment induced
      interleukin-1beta-like immunoreactivity in immune cells that either associated
      with the vasculature (perivascular cells, a subtype of macrophage) or associated
      with neuronal elements (dendritic-like, and unknown phenotype). Electron
      microscopic analysis revealed that some immune cells, including interleukin-1beta
      positive cells, evinced membrane apposition with neuronal elements, including
      dendrites and terminals, that could derive from inputs to the area postrema such
      as vagal sensory fibers, or intrinsic area postrema neurons. This arrangement
      provides an anatomical substrate by which immune cells could directly and
      specifically influence individual neurons in the area postrema, that may support
      the induction and/or maintenance of brain responses to inflammation.

PMID- 16650943
TI  - Neural pathways involved in the endocrine response of anestrous ewes to the male
      or its odor.
AB  - During the non-breeding season, anestrous ewes do not experience ovarian cycles
      but exposure to a ram or its odor results in the activation of the luteinizing
      hormone secretion leading to ovulation. The aim of our work was to identify the
      neural pathways involved in this phenomenon. Using Fos immunocytochemistry, we
      examined the brain areas activated by the male or its fleece, in comparison with
      ewes exposed to the female fleece or the testing room (control group). In
      comparison with the control group, the male or its odor significantly increases
      Fos neuronal expression in the main and accessory olfactory bulbs, anterior
      olfactory nucleus, cortical and basal amygdala, dentate gyrus, ventromedial
      nucleus of the hypothalamus, piriform and orbitofrontal cortices. The main
      olfactory bulb, the cortical amygdala and the dentate gyrus are specifically more
      activated by the male odor than the female odor. Using a procedure of double
      labeling for Fos and gonadotropin-releasing hormone, we also compared the number
      of gonadotropin-releasing hormone neurons activated in the four groups of
      females. The male or its odor significantly increases the number and the
      proportion of gonadotropin-releasing hormone cells expressing Fos
      immunoreactivity in the preoptic area and the organum vasculosum of the lamina
      terminalis, whereas no such induction of Fos-immunoreactivity was found in
      gonadotropin-releasing hormone neurons of ewes exposed to the female odor or the
      testing room. These findings emphasize the role of the main olfactory system in
      the detection and the integration of the ram odor, and also suggest the
      participation of the accessory olfactory system. Numerous structures widely
      distributed seem involved in the processing of the male olfactory cue to reach
      the gonadotropin-releasing hormone neurons.

PMID- 16650944
TI  - Single nucleotide polymorphisms in the chicken Lmbr1 gene are associated with
      chicken polydactyly.
AB  - Polydactyly is a common malformation of vertebrate limbs. Preaxial polydactyly
      (PPD) has been mapped in human, mouse and chicken to the syntenic region of human
      7q36. Lmbr1 was thought as the critical candidate gene for human and mouse PPD.
      To understand the molecular mechanism underlying chicken polydactyly, we have
      cloned the open reading frame (ORF) of chicken Lmbr1, which contains 1467
      nucleotides. Within this ORF, we found one short and one long splice forms. The
      short splice form has a complete deletion of exon 4. Six cSNPs were found in the
      chicken ORF, and two of these cSNPs, G797A and G1255A, lead to amino acid
      substitutions. However, G797A substitution had no significant association with
      polydactyly and the G1255A substitution had very low frequency in the population.
      The T1254C polymorphism in exon 13 was found to be strongly associated with
      polydactyly. Radiation hybrid mapping of a DNA fragment containing intron 13 of
      the chicken Lmbr1 assigned the gene to chromosome 2 between MCW071 (a marker
      within the EN2 gene) and ADL0270, a syntenic region to human 7q36.

PMID- 16650945
TI  - Identification and immunological characterization of conserved Mycoplasma
      hyopneumoniae lipoproteins Mhp378 and Mhp651.
AB  - Mycoplasma hyopneumoniae, the etiological agent of swine enzootic pneumonia, is
      an important pathogen in the swine industry worldwide. Investigations on
      pathogenicity mechanisms as well as current serological detection methods and the
      development of new recombinant subunit vaccines are hampered by the lack of known
      and well characterized, species-specific M. hyopneumoniae antigens. As a first
      step to solve these problems membrane and membrane-associated proteins were
      enriched from M. hyopneumoniae cells by Triton X-114 fractionation and further
      analyzed by 2D gel electrophoresis and Western blot analyses using convalescent
      sera. Two previously unknown immunogenic proteins were identified by quadrupole
      time-of-flight mass spectrometry and database analyses as the conserved putative
      lipoproteins, Mhp378 and Mhp651. Both proteins were expressed as recombinant GST
      fusion proteins and reacted with sera from convalescent pigs. Coated as solid
      phase antigen, Mhp651 showed a distinct cross-reaction only with Mycoplasma
      flocculare specific rabbit hyperimmune serum, whereas Mhp378 was only recognized
      by the positive control serum directed against M. hyopneumoniae, thereby
      indicating its species specificity.

PMID- 16650947
TI  - Acoustic quality of cry in very-low-birth-weight infants at the age of 1 1/2
      years.
AB  - BACKGROUND: Infant cry characteristics reflect the integrity of the central
      nervous system. Previous studies have shown that preterm infants and infants with
      neurological conditions have different cry characteristics such as fundamental
      frequency compared to healthy full-term infants. Cry characteristics of preterm
      infants after the first year of life have not been studied. AIMS: The aim of this
      study was to assess the quality of cry in 1 1/2-year-old very-low-birth-weight
      infants (VLBWI, < or =1500 g at birth). STUDY SUBJECTS AND DESIGN: Study groups
      included 21 VLBWI and 25 healthy full-term controls. Thirty seconds of pain cry
      after vaccination was recorded at well-baby clinics. The first cry utterance was
      acoustically analyzed using Praat software. The quality of cry was compared
      between the groups. In addition, the association of cry quality to patient
      characteristics, to developmental outcome, and to findings in brain imaging
      studies of the VLBWI was studied. RESULTS: The cry response was elicited in 20 of
      the 21 VLBWI and in 20 out of 25 full-term infants. VLBWI had higher minimum
      fundamental frequency and fourth formant values. Patient characteristics that
      were associated with cry quality were 5-min Apgar scores, the occurrence of
      bronchopulmonary dysplasia, Bayley Psychomotor Index scores at 12 months, and
      current weight and head circumference. CONCLUSIONS: Differences found between the
      study groups were not explained primarily by brain pathology or by patient
      characteristics, so it seems that prematurity has an impact on cry quality still
      at the age of 1 1/2 years.

PMID- 16650948
TI  - Psychiatric morbidity is related to a chain of prenatal and perinatal
      adversities.
AB  - BACKGROUND: Most studies on the effects of early risk factors on future mental
      health focus on specific obstetric complications as risk factors for specific
      disorders. However, obstetric complications rarely occur in isolation, and the
      same holds for psychiatric problems. AIMS: To study prenatal and perinatal risk
      factors for psychiatric multimorbidity in early adulthood and to determine
      whether these differ from risk factors for monomorbidity. STUDY DESIGN:
      Monomorbidity and multimorbidity of six types of psychiatric disorders were
      determined by a standardised psychiatric interview. Using univariate and
      multivariate logistic and ordinal logistic regression, associations of mono- and
      multimorbidity with prospectively collected early risk factors were examined.
      SUBJECTS: Two hundred and eighty-five young adults selected from a prospective
      birth cohort on the basis of their Obstetric Optimality Scores. OUTCOME MEASURES:
      Six types of psychiatric disorder and their co-occurrence. RESULTS: Monomorbidity
      was related to isolated early risk factors such as low birth weight or a low
      Apgar score, and to an accumulation of unfavourable pre- and perinatal events.
      Multimorbidity on the other hand, was only related to a chain of pre- and
      perinatal adversities. CONCLUSION: Research and prevention strategies should not
      focus solely on isolated early risk factors, but also on the entire pre- and
      perinatal situation.

PMID- 16650949
TI  - General movement assessment: predicting cerebral palsy in clinical practise.
AB  - OBJECTIVE: The general movement assessment (GMA) method is used to predict
      cerebral palsy (CP) in infants with high risk of developing neurological
      dysfunctions. Most of the work on GMA has been performed from the same group of
      researchers. The aim of this study was to demonstrate to what extent GMA
      predicted CP in our hands. METHOD: A prospective study was performed using the
      Prechtl classification system for GMA in the fidgety period to predict later
      cerebral palsy. The study population consisted of 74 term and preterm infants at
      low and high risk of developing neurological dysfunction. The absence or presence
      of CP was reported at 23 months median-corrected age by the child's physician and
      the parents. RESULTS: The GMA identified all 10 infants that later were
      classified as having CP. GMA also identified all the infants that did not develop
      CP except for one infant with abnormal GMA and no CP. Three infants had uncertain
      CP status at follow-up. The sensitivity of GMA with regard to later CP was 100%
      with 95% CI (0.73, 1.00) and the specificity was 98% with 95% CI (0.91, 0.99)
      when the three uncertain cases were excluded. CONCLUSION: Our study indicates
      that the GMA used in a clinical setting strongly predicts the development of CP.
      The work supports the results of previous studies and contributes to the
      validation of GMA. The qualitative nature of this method may be a problem for
      inexperienced observers. Larger clinical studies are needed.

PMID- 16650950
TI  - Wischnewsky's spots in an ectopic stomach.
AB  - Wischnewsky's spots in the mucosa of the stomach have been a well-known sign of
      death due to hypothermia for many years. Furthermore it is reported that those
      spots can rarely be found in the esophagus as well. We now report on a case
      concerning a 93-year-old woman who presented an ectopic stomach with erosions of
      the mucosa in the intrathoracic part of the stomach that were assessed as
      Wischnewsky's spots. When she was found dead in her flat, she was completely
      undressed and showed an injury to the head. The autopsy findings are presented
      and discussed in view of a possible genesis and pathophysiology of Wischnewsky's
      spots.

PMID- 16650951
TI  - Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram
      negative clinical strains from North American Hospitals: report from the SENTRY
      Antimicrobial Surveillance Program (1998-2004).
AB  - To assess the effect of ceftazidime resistance on the activity of other
      antimicrobial agents, 3030 ceftazidime-resistant Gram-negative bacilli (GNB)
      isolates (of a total of 42061 GNB) were tested against a panel of more than 30
      agents. Ceftazidime resistance was observed in 40.3% of Acinetobacter spp., 16.9%
      of Pseudomonas aeruginosa, and 5.7% of Enterobacteriaceae isolates. The highest
      rates of ceftazidime resistance among the enteric GNB were observed with
      Enterobacter spp. (20.9%) >Citrobacter spp. (15.3%) > indole-positive Proteae
      (10.1%). Overall, 90% of ceftazidime-resistant Enterobacteriaceae and 30% of
      ceftazidime-resistant P. aeruginosa remained susceptible to the "4th-generation"
      cephalosporin, cefepime. The activities (% susceptible) of other antimicrobials
      tested against ceftazidime-resistant Enterobacteriaceae and P. aeruginosa,
      respectively, were as follows: amikacin, 90% and 88%; ciprofloxacin, 63% and 46%;
      gentamicin, 59% and 67%, imipenem, 99% and 65%; levofloxacin, 69% and 44%; and
      piperacillin/tazobactam only 40% and 12%. Ceftazidime-resistant GNB exhibited
      high rates of resistance to other antimicrobials. Cefepime was very active
      against ceftazidime-resistant enteric GNB (AmpC enzyme producers), especially
      Enterobacter spp. (94.3% susceptible), Citrobacter spp. (96.7% susceptible), and
      indole-positive Proteae (89.6% susceptible), and showed activity similar to that
      of ceftazidime against all P. aeruginosa and Acinetobacter spp. isolated in North
      American medical centers. Continued resistances surveillance monitoring will be
      necessary to assess the effectiveness of widely used broad-spectrum
      antimicrobials as novel resistance mechanisms emerge.

PMID- 16650952
TI  - Spontaneous peritonitis caused by Leminorella grimontii.
AB  - A case of spontaneous peritonitis caused by Leminorella grimontii in a 63-year
      old man with cirrhosis is reported. To our knowledge, L. grimontii has never been
      reported as a cause of spontaneous bacterial peritonitis. The patient responded
      to antimicrobial therapy. Clinical and therapeutic implications are discussed.

PMID- 16650953
TI  - Comparison of Sensititre YeastOne with the NCCLS M38-A microdilution method to
      determine the activity of amphotericin B, voriconazole, and itraconazole against
      clinical isolates of Aspergillus fumigatus.
AB  - The in vitro activities of amphotericin B, itraconazole, and voriconazole against
      279 clinical isolates of Aspergillus fumigatus were studied by comparing
      Sensititre YeastOne with the reference method NCCLS (CLSI) M38-A. The methods
      were considered to agree when the results of the MICs by Sensititre were within 2
      dilutions of the MICs obtained by NCCLS M38-A. Agreement of readings at 24, 48,
      and 72 h was as follows: amphotericin B (0%, 31.5%, 82.1%), itraconazole (86.7%,
      98.3%, 98.2%), and voriconazole (92.8%, 98.3%, 98.9%). Sensititre YeastOne is a
      suitable alternative for the determination of the MICs of itraconazole and
      voriconazole against A. fumigatus when results are read at 48 h of incubation.

PMID- 16650954
TI  - Simultaneous species identification and detection of methicillin resistance in
      staphylococci using triplex real-time PCR assay.
AB  - For rapid identification of methicillin-resistant Staphylococcus aureus,
      molecular methods are generally targeting mecA and species-specific genes. Sa442
      DNA fragment is a popular species-specific target. However, recently, there have
      been few reports on S. aureus isolates that are negative for Sa442 fragment;
      therefore, use of single gene or DNA-fragment-specific polymerase chain reaction
      (PCR) for identification of microbial isolate may result in misidentification.
      This study includes CoA gene in parallel with Sa442 marker for identification of
      S. aureus. This further improves the specificity of the assay by checking for 2
      determinants simultaneously for the identification of S. aureus and can prevent
      misidentification of S. aureus isolates lacking Sa442 DNA fragment. In this
      study, the newly developed triplex real-time PCR assay was compared with a
      quadruplex conventional gel-based PCR assay using the same primer sets in both
      assays. The dual-labeled TaqMan probes (ProOligo, France) for these primers were
      specifically designed and used in a real-time PCR assay. The clinical isolates (n
      = 152) were subjected to both PCR assays. The results obtained from both assays
      proved that the primer and probe sets were 100% sensitive and 100% specific for
      identification of S. aureus and detection of methicillin resistance. This triplex
      real-time PCR assay represents a rapid and powerful method for S. aureus
      identification and detection of methicillin resistance.

PMID- 16650955
TI  - Biochemical and immunologic features of an outbreak of Legionnaires disease:
      comparative study between community-acquired pneumonias.
AB  - Legionella pneumophila has been recognized as an important cause of community-
      and hospital-acquired pneumonia. This study evaluates the interrelationship
      between that patients group with Legionnaires disease (LD) and the possible
      factors that may predispose hosts to acquire this infection. Likewise, we search
      for preliminary biochemical and immunologic evidences that could help physicians
      to differentiate between LD and other pneumonias. We analyzed biochemical
      parameters and immunoglobulin levels in 61 LD patients and a control group (n =
      30) who were non-Legionella pneumonia diagnosed. We observed statistically
      significant differences in LD patients versus control group in serum sodium,
      albumin, gamma-band, IgG levels, (P < .01) and for total proteins, aspartate
      aminotransferase (AST), and lactate dehydrogenase (LDH) (P < .05). Our study
      shows a trend between the presence of LD and immunoglobulin deficiencies in the
      group studied. Deficit in IgG or IgG plus IgM, during the exposure period, may
      predispose individuals to suffer legionellosis (P < .05). Overall,
      hypoalbuminemia, hyponatremia, and high AST and LDH levels can represent a useful
      prognostic marker in patients with severe pulmonary infection suspected to be
      legionellosis.

PMID- 16650956
TI  - Single-stranded conformation polymorphism of large subunit of ribosomal RNA is
      best suited to diagnosing fungal infections and differentiating fungi at species
      level.
AB  - In the last decade, various polymerase chain reaction (PCR)-based methods have
      been developed using ribosomal RNA (rRNA) for the identification of medically
      important fungi. In the present study, large subunit (LSU) and small subunit
      (SSU) of fungal rRNA were amplified and analyzed by single-stranded conformation
      polymorphism (SSCP) of nested PCR, restriction digestion, and SSCP of digested
      products. The relationship between several clinical isolates of patients
      suffering from aspergillosis, candidiasis, cryptococcosis, keratitis, and skin
      and nail infections has been established with standard fungal cultures using the
      SSU- and LSU-specific primers. Single-stranded conformation polymorphism of
      restriction profile of amplified products of LSU-specific primers was
      successfully used to differentiate fungi up to genus and species level.

PMID- 16650957
TI  - Prevalence of enterotoxigenic Bacteroides fragilis in hospital-acquired diarrhea.
AB  - Stool specimens from 152 hospitalized patients with diarrhea were analyzed for
      the presence of enterotoxigenic Bacteroides fragilis (ETBF) by a nested
      polymerase chain reaction (PCR) assay. ETBF gene sequences were directly detected
      in 14/152 (9.21%) stools of patients. The prevalence of ETBF in hospital-acquired
      diarrhea was statistically significant when compared to a prevalence of 2.3% in
      control subjects (P = 0.04). B. fragilis was cultured from 19.7% (30/152)
      patients with diarrhea; 4 of these isolates were enterotoxigenic. To determine
      whether colonization with B. fragilis is heterogeneous in nature, multiple
      colonies from 17 individual patients were analyzed for enterotoxin gene sequences
      and genotyped by arbitrarily primed PCR. Of these 17 patients, 13 harbored
      multiple strain types suggesting heterogeneity of colonization with both
      enterotoxigenic and non-enterotoxigenic strains. Identification of ETBF in the
      stools of 10 patients in the absence of a positive culture is likely due to the
      noted heterogeneity and suggests that detection of enterotoxin by PCR should be
      performed directly in the stool. These preliminary data indicate that ETBF may
      play a role in hospital-acquired diarrhea of unknown origin and suggest the need
      for further studies.

PMID- 16650958
TI  - Native-valve bacterial endocarditis caused by Lactococcus garvieae.
AB  - We report a case of definite Lactococcus garvieae native-valve endocarditis. The
      diagnosis was suspected in a patient presenting with congestive heart failure and
      found to have Enterococcus hirae bacteremia, with a history of L. garvieae
      bacteremia 1 month prior. Diagnosis was confirmed by 16S rRNA gene sequencing of
      the 2 isolates and the demonstration of aortic valve vegetations.

PMID- 16650959
TI  - Recurrent granulomatous tenosynovitis of the wrist and finger caused by
      Mycobacterium intracellulare: a case report.
AB  - We report a 65-year-old man with tenosynovitis of the wrist and finger caused by
      Mycobacterium intracellulare. The diagnosis was made after subsequent recurrence,
      when a specimen of synovial fluid was subjected to specific polymerase chain
      reaction and mycobacterial culture. Synovectomy and susceptibility-guided
      antituberculous therapy permitted complete healing of tenosynovitis.

PMID- 16650960
TI  - Hepatic bisegmentectomy 7-8 for a colorectal metastasis.

PMID- 16650961
TI  - Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal
      cancer metastatic liver disease.
AB  - AIMS: The degradation of the extracellular matrix is intrinsic to the invasion
      and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their
      natural inhibitors are involved in this process. The study aims to investigate if
      plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be
      useful markers in the diagnosis and prognosis of colorectal cancer (CRC)
      metastatic liver disease. METHODS: Fifty-seven patients undergoing liver
      metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma
      levels were determined by zymography and ELISA, before and after the resection of
      liver metastases. Data were compared with those of healthy controls (n=51) and
      primary CRC patients (n=94). The diagnostic and prognostic potential was
      investigated with ROC-curves and Kaplan-Meier survival analysis. RESULTS: Plasma
      proMMP-2 levels were lower (P<0.001), and TIMP-1 levels higher (P<0.001) in CRC
      metastatic liver disease than in healthy controls. If compared to those in
      primary CRC patients, no differences were found. In ROC-curves, the area under
      the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, 
      9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and
      prognostic examinations, CEA proved to be a better marker. In the postoperative
      follow-up, protracted low levels of proMMP-2 seemed related to disease
      recurrence. CONCLUSION: The preoperative plasma proMMP-2, -9 and TIMP-1 levels
      have no potential value as diagnostic or prognostic markers in CRC liver
      metastatic disease.

PMID- 16650962
TI  - High incidence of BRCA1-2 germline mutations, previous breast cancer and familial
      cancer history in Jewish patients with uterine serous papillary carcinoma.
AB  - OBJECTIVE: To test the carrier status of the three germline founder mutations in
      Jewish patients with uterine serous papillary carcinoma (USPC) and to evaluate
      its association to their personal and familial cancer records. METHODS:
      Retrospective analysis of histologically confirmed USPC Jewish patients diagnosed
      between April 1, 1997 and December 31, 2003. All cases were genetically tested
      for the three BRCA1-2 founder germline mutations (185delAG and 5382insC in BRCA1
      and 6174delT in BRCA2). The analysis was performed on genomic DNA extracted from
      whole blood or paraffin embedded normal tissue of these patients, employing PCR
      amplification of target sequences and differential digestion with restriction
      enzymes. The carrier frequency was compared to the known population frequency of
      these mutations. RESULTS: The study group comprised 22 Jewish patients with USPC
      diagnosed within this timeframe. The mean age was 71.8 years (range 56-79). FIGO
      surgical stage distribution revealed 59% at stages III-IV. Seven USPC patients
      (32%) with a previous diagnosis of breast cancer were identified. Familial cancer
      history was recorded in 23% of the patients (four with breast cancer and one with
      ovarian cancer). DNA analysis revealed six BRCA1-2 germline mutation carriers
      (27%) as follows: three with BRCA2-6174delT, two with BRCA1-185delAG, and one
      with BRCA1-5382insC mutation. Three of the carriers had a previous diagnosis of
      breast cancer. Four carriers had familial cancer history in first-degree relative
      (three with breast cancer and one with ovarian cancer). CONCLUSIONS: The high
      rate of BRCA germline mutations in USPC patients observed in the present study,
      coupled with the strong personal and familial cancer history as well as the
      histological and clinical resemblance to the ovarian cancer, may indicate that
      USPC is a part or an expression of the hereditary breast-ovarian cancer syndrome.
      This option may have implications in our clinical recommendations for non
      affected BRCA1-2 carriers.

PMID- 16650963
TI  - Cyclo-oxygenase-2 (COX-2) mRNA expression and hormone receptor status in breast
      cancer.
AB  - AIMS: The purpose of this study was to evaluate COX-2 mRNA expression with known
      clinical prognostic features of breast cancer, oestrogen/progesterone receptor
      status, tumour size and grade. METHODS: Total RNA was extracted from 45 frozen
      breast tumour (invasive) and 22 normal breast tissue samples. COX-2 mRNA
      transcription was quantified using a real time RT-PCR assay and expressed as copy
      number/microg total RNA. All specimens were assessed for tumour grade, size,
      nodal status and presence of vascular invasion and oestrogen and progesterone
      receptor status. RESULTS: COX-2 mRNA was detected in all samples with a median
      copy number of 1.15 x 10(7) for tumours and 6.5 x 10(6) for normal samples.
      Expression was significantly higher in oestrogen receptor negative tumours
      compared to the receptor positive group. There was no correlation between COX-2
      mRNA levels and tumour size, grade, nodal status and presence of vascular
      invasion. CONCLUSIONS: COX-2 mRNA expression is increased in oestrogen and
      progesterone receptor negative breast cancers.

PMID- 16650964
TI  - Structure, developmental course, and correlates of children's anxiety disorder
      related behavior in a Hellenic community sample.
AB  - The generality of the DSM-IV diagnostic structure for children's anxiety
      disorders, as measured by the Spence Children's Anxiety Scale (SCAS) was
      investigated with a Greek-language version of the scale. An exploratory factor
      analysis produced a six-factor solution in general accord with the DSM-IV-based
      theoretical structure of responding. However, a generalized anxiety factor
      incorporated three unexpected items interpreted as representing excessive worry,
      including two items intended to measure obsessions, raising the question of
      children's ability to discriminate the intrusiveness of vexatious cognition.
      Anxiety scores were negatively correlated with school adjustment and performance,
      and decreased with age, with the exception of social phobia scores, which
      increased. Anxiety scores were substantially higher than those observed in most
      cultures, particularly on social phobia and compulsive behavior subscales.
      Hellenic children might regard compulsive behaviors as more socially acceptable
      than other anxiety disorder-related behaviors, whereas higher overall anxiety
      scores appear to be related to socio-economic circumstances.

PMID- 16650965
TI  - Asn229 in the third helix of VPAC1 receptor is essential for receptor activation
      but not for receptor phosphorylation and internalization: comparison with Asn216
      in VPAC2 receptor.
AB  - After stimulation with agonist, G protein coupled receptors (GPCR) undergo
      conformational changes that allow activation of G proteins to transduce the
      signal, followed by phosphorylation by kinases and arrestin binding to promote
      receptor internalization. Actual paradigm, based on a study of GPCR-A/rhodopsin
      family, suggests that a network of interactions between conserved residues
      located in transmembrane (TM) domains (mainly TM3, TM6 and TM7) is involved in
      the molecular switch leading to GPCR activation. We evaluated in CHO cells
      expressing the VPAC(1) receptor the role of the third transmembrane helix in
      agonist signalling by point mutation into Ala of the residues highly conserved in
      the secretin-family of receptors: Y(224), N(229), F(230), W(232), E(236), G(237),
      Y(239), L(240). N(229)A VPAC(1) mutant was characterized by a decrease in both
      potency and efficacy of VIP stimulated adenylate cyclase activity, by the absence
      of agonist stimulated [Ca(2+)](i) increase, by a preserved receptor recognition
      of agonists and antagonist and by a preserved sensitivity to GTP suggesting the
      importance of that residue for efficient G protein activation. N(229)D mutant was
      not expressed at the membrane, and the N(229)Q with a conserved mutation was less
      affected than the A mutant. Agonist stimulated phosphorylation and
      internalization of N(229)A and N(229)Q VPAC(1) were unaffected. However, the re
      expression of internalized mutant receptors, but not that of the wild type
      receptor, was rapidly reversed after VIP washing. Receptor phosphorylation,
      internalization and re-expression may be thus dissociated from G protein
      activation and linked to another active conformation that may influence its
      trafficking. Mutation of that conserved amino acid in VPAC(2) could be
      investigated only by a conservative mutation (N(216)Q) and led to a receptor with
      a low VIP stimulation of adenylate cyclase, receptor phosphorylation and
      internalization. This indicated the importance of the conserved N residue in the
      TM3 of that family of receptors.

PMID- 16650966
TI  - ARF6 activation by Galpha q signaling: Galpha q forms molecular complexes with
      ARNO and ARF6.
AB  - G protein-coupled receptors (GPCRs) are widely expressed hepta-helical receptors
      with tightly regulated pleiotropic effects. ADP-Ribosylation Factor 6 (ARF6)
      plays an important role in GPCR trafficking and is the subject of intense
      research. However, the mechanisms underlying activation and regulation of ARF6 by
      GPCRs are poorly characterized. Here we report that Galpha(q) signaling leads to
      the activation of ARF6. Stimulation of the TPbeta receptor triggered ARF6
      activation which was completely inhibited by the RGS domain of GRK2 known to
      specifically bind and sequester Galpha(q). Co-immunoprecipitation studies
      revealed that ARNO (a guanine nucleotide exchange factor for ARF6) and ARF6
      formed complexes preferentially with activated Galpha(q) compared to non
      activated Galpha(q). Formation of the Galpha(q) complexes with ARNO and ARF6 was
      detected early and was optimal after 30 min of receptor stimulation corresponding
      with the profile of ARF6 activation. Interestingly, binding experiments using
      purified proteins showed that Galpha(q) interacted directly with ARNO. Galpha(q)
      dependent TPbeta receptor-mediated activation of ARF6 resulted in phosphoinositol
      4,5-bisphosphate production which was potently inhibited by dominant negative
      mutants of ARNO and ARF6. Furthermore, our data show that the expression of ARNO
      and ARF6 promoted, whereas dominant negative mutants of these proteins inhibited
      the internalization of the TPbeta receptor. This further elucidates our previous
      data on the PLCbeta- and PKC-independent mechanism involved in Galpha(q)-mediated
      internalization of the TPbeta receptor. Taken altogether, our results support a
      novel model where activated Galpha(q) forms molecular complexes with ARNO and
      ARF6, possibly through a direct interaction with ARNO, leading to ARF6
      activation.

PMID- 16650967
TI  - Accelerometry is a valid measure of physical inactivity but not of energy
      expended on physical activity in people with schizophrenia.

PMID- 16650968
TI  - Impaired attention is central to the cognitive deficits observed in alpha 7
      deficient mice.
AB  - alpha7-Nicotinic acetylcholine receptors (alpha7-nAChR) have been implicated in a
      range of cognitive deficits in schizophrenia. Therefore we examined alpha7-nAChR
      knockout (KO), heterozygote (HT) and wildtype (WT) littermate mice in the 5-CSR
      (a rodent model of sustained attention) and odour span (a novel mouse working
      memory paradigm) tasks, and related performance to nAChR density. Whilst there
      was no difference between groups in baseline 5-CSR task performance, alpha7-nAChR
      KO's exhibited significantly higher omission levels compared to WT mice on
      increasing the attentional load, with HT mice performing at an intermediate
      level. Furthermore, alpha7-nAChR KO mice were significantly impaired in the odour
      span task when compared to WT mice, in a pattern consistent with impaired
      attention. These behavioural deficits were associated with the loss of alpha7
      nAChRs, as alpha4beta2-nAChR density was unaltered in these mice. Thus these
      studies intimate that the attentional impairment in alpha7-nAChR transgenic mice
      maybe core to other deficits in cognition.

PMID- 16650969
TI  - Effect of n-3 and n-6 polyunsaturated fatty acids on lymphocyte proliferation,
      interleukin production and phospholipid fatty acids composition in type 2
      diabetic and healthy subjects in Jordan people.
AB  - Dietary lipid manipulation may affect a great number of immune parameters, such
      as lymphocyte proliferation, cytokine synthesis. In this study, lymphocytes of
      diabetic type 2 were incubated with different polyunsaturated fatty acid
      (docosahexaenoic, eicosapentaenoic, arachidonic acid) for investigated their
      effect on lymphoproliferation response, the concentration of interleukin 2
      produced in each essay and phospholipid fatty acid composition of lymphocyte
      membrane. Our results found that the concanavalin A and insulin increase
      significantly the proliferative response while eicosapentaenoic, arachidonic and
      docosahexaenoic acid inhibited that by different degrees: 47%, 37% and 19%,
      respectively, for healthy subjects and 39%, 29% and 13% for diabetes. However,
      the concentration of IL-2 produced in presence of either docosahexaenoic,
      eicosapentaenoic or arachidonic acid was significantly reduced by 36%, 32% and
      39%, respectively, in controls while 16%, 15% and 23%, respectively, in
      diabetics. On the other hand, the tested fatty acids demonstrated a major impact
      on the fatty acid composition of different phospholipid fractions of lymphocyte
      membrane but these fractions were different in their response to each fatty acid
      examined. For instance, the addition of docosahexaenoic acid to culture media was
      accompanied with a predominant composition of docosahexaenoic acid in
      phospholipid fractions. Also, our results showed a notable increased proportion
      of arachidonic, eicosapentaenoic and docosahexaenoic acids in control
      phospholipid fractions than those of diabetic.

PMID- 16650970
TI  - Characterisation of the onset and presenting clinical features of adult
      bronchiectasis.
AB  - BACKGROUND: There is little information available on the features of initial
      presentation of bronchiectasis and documentation of the onset and progress of
      symptoms leading up to this. Therefore a study was performed on a large cohort of
      adult patients presenting to Monash Medical Centre (MMC) to survey the course of
      their disease up to the time of diagnosis. OBJECTIVES: To characterise the onset
      and presenting clinical features of bronchiectasis in adults. METHODS: A cross
      sectional study of 103 adults presenting to a tertiary referral hospital with
      newly diagnosed bronchiectasis. Clinical features of bronchiectasis and results
      of spirometry, sputum microbiology and radiology were assessed and correlated.
      RESULTS: Most patients had idiopathic bronchiectasis (74%) and did not have other
      significant disease. The dominant symptom was chronic productive cough present in
      98% of patients with other important symptoms being chronic rhinosinusitis (70%),
      dyspnoea (62%), and fatigue (74%). Most patients had had a chronic productive
      cough for over 30 years prior to diagnosis and over 80% of patients had chronic
      respiratory symptoms from childhood. The dominant finding on physical examination
      was the presence of crackles which were generally bi-basal. Spirometry showed
      mild airway obstruction with an average forced expiratory volume in 1s of the
      cohort of 76% predicted. Radiologic imaging generally showed multilobar disease
      (80%). CONCLUSIONS: The typical profile of bronchiectasis in this group of
      patients was of longstanding productive cough, rhinosinusitis and fatigue in non
      smokers with crackles on chest auscultation.

PMID- 16650971
TI  - Genetic and environmental contributions to hay fever among young adult twins.
AB  - BACKGROUND: The susceptibility to develop hay fever is putatively the result both
      of genetic and environmental causes. We estimated the significance and magnitude
      of genetic and environmental contributions to hay fever among young adult twins.
      METHODS: From the birth cohorts 1953-82 of The Danish Twin Registry 11,750 twin
      pairs were identified through a nationwide questionnaire survey. Subjects were
      regarded hay fever cases when responding affirmatively to the question 'Do you
      have, or have you ever had hay fever?' Latent factor models of genetic and
      environmental effects were fitted to the observed data using maximum likelihood
      methods. RESULTS: The overall cumulative prevalence of hay fever was 12.6%.
      Identical twins were significantly more likely to be concordant for hay fever
      than were fraternal twins (P<0.001). Additive genetic effects accounted for 71%
      and non-shared environmental effects accounted for 29% of the individual
      susceptibility to hay fever. The same genes contributed to the susceptibility to
      hay fever both in males and in females. In families with asthma, the
      susceptibility to develop hay fever was, in addition to genes, to a great extent
      ascribable to family environment, whereas the aetiology of 'sporadic' hay fever
      was mainly genetic. CONCLUSIONS: The susceptibility to develop hay fever is
      attributable to major genetic influences. However, effects of family environment
      and upbringing are also of importance in families where asthma is present. These
      results indicate that different sub-forms of hay fever may have different
      aetiologies.

PMID- 16650972
TI  - Change in C-reactive protein levels and FEV1 decline: a longitudinal population
      based study.
AB  - Reduced pulmonary function is an important predictor of cardiovascular morbidity
      and mortality. The mechanisms underlying this association are unknown but may
      involve systemic inflammation. We assessed the cross-sectional and longitudinal
      relationships between C-reactive protein (CRP) levels and forced expiratory
      volume in 1s (FEV1) and its decline in the general population, over a period of
      8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37+/-7
      years, 50% women and 42% non-smokers), recruited at two French centers
      participating in the European Community Respiratory Health Survey. Lung function
      was expressed as a percentage of predicted FEV1. CRP was measured centrally, by
      means of a highly sensitive assay. In cross-sectional analysis, FEV1 as a % of
      predicted values was negatively associated with serum CRP concentration
      (P=0.002). Multivariate adjustment did not alter these results (P=0.002). In
      longitudinal analysis, annual FEV1 decline tended to increase from the lower to
      the upper tertile for baseline CRP concentration but the association was
      borderline significant (P=0.14). Mean values of annual FEV1 decline were 26+/-32,
      31+/-32, and 34+/-32 ml/year for the lower, middle and upper tertiles of baseline
      CRP concentration, respectively, after adjusting for potential confounders
      (P=0.09). Changes in CRP levels during follow-up were associated with annual FEV1
      decline. The mean annual FEV1 declines in subjects with increasing CRP, in those
      with stable CRP and in those with decreasing CRP were 36+/-31, 30+/-31 and 24+/
      31 ml/year, respectively (P<0.001). These findings were not affected by
      adjustment for potential confounders (P=0.002). In conclusion, increases in CRP
      levels over time were associated with a steeper FEV1 decline.

PMID- 16650973
TI  - Correlation between survivin expression and prognosis in non-small cell lung
      cancer.
AB  - AIMS AND BACKGROUND: Survivin is a recently identified protein as an inhibitor of
      apoptosis, which supresses programmed cell death and regulates cell division. In
      this study, we investigated the prognostic significance of both nuclear and
      cytoplasmic survivin expression in non-small cell lung cancer (NSCLC) and
      examined the association with clinicopathological parameters. METHODS: The study
      comprised 58 male patients diagnosed NSCLC with a mean age of 57.29+/-8.82 years;
      range 40-76 years. Patients underwent lobectomy (64%) or pneumonectomy (36%) with
      hilar and mediastinal lymph node sampling. Paraffin embedded tumor sections were
      retrieved for evaluation of nuclear and cytoplasmic staining of survivin.
      Clinicopathological data, stage and survival of patients were all determined.
      RESULTS: Cytoplasmic staining was found significantly increased in squamous cell
      carcinoma (P=0.003), whereas there was no association between nuclear staining
      and histopathological type (P=0.837). Also, both nuclear and cytoplasmic staining
      did not show any association with tumor stage (P>0.05). In univariate analysis
      there was significant correlation between nuclear survivin and short survival
      (P=0.0002). In multivariate survival analysis using Cox regression, only nuclear
      staining of survivin was determined as an independent prognostic factor
      (P=0.004). CONCLUSIONS: Localization of survivin expression might have an
      important regulatory mechanism in carcinogenesis and tumor progression. Nuclear
      survivin expression in tumor tissues might predict the prognosis in NSCLC,
      whereas cytoplasmic survivin has no prognostic significance.

PMID- 16650974
TI  - Effect of CPAP on brachial-ankle pulse wave velocity in patients with OSAHS: an
      open-labelled study.
AB  - Pulse wave velocity (PWV) is a good indicator of arterial stiffness and an
      important predictor of cardiovascular events. Recent studies have revealed that
      PWV increases in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)
      and it also correlates with its severity. However, the therapeutic effect of
      continuous positive airway pressure (CPAP) on PWV remains undetermined. To
      clarify this point, we started CPAP treatment on 17 OSAHS patients. Brachial
      ankle PWV was measured before starting CPAP, and at 2 months and 4 months after
      the start of CPAP. Before the CPAP treatment, mean brachial-ankle PWV of the
      patients was 15.6+/-0.6 m/s, and mean Epworth sleepiness scale (ESS) score was
      8.6+/-1.0. Brachial-ankle PWV was found to positively correlate with heart rate,
      systolic and diastolic blood pressures, mean blood pressure, and arousal index.
      During the study period, the CPAP treatment did not have a significant effect on
      heart rate, blood pressures and serum total cholesterol levels. However, it
      significantly improved ESS score at 4 months after the start of CPAP (P=0.001),
      while it effectively decreased brachial-ankle PWV at 2 months and at 4 months
      after the start of CPAP (P=0.010 and P=0.027, respectively). The CPAP treatment
      was shown to decrease brachial-ankle PWV without affecting blood pressures in
      OSAHS patients. Although the precise mechanism for this effect is unclear, our
      finding suggests a close relationship between OSAHS and arterial stiffness, while
      also reemphasizing the clinical importance of CPAP treatment.

PMID- 16650975
TI  - Economic aspects of antimicrobial therapy of acute exacerbations of COPD.
AB  - This article synthesizes and appraises the methodological quality of the
      international literature on costs of chronic obstructive pulmonary disease (COPD)
      exacerbations, economic value of antimicrobial therapy of exacerbations, and
      factors affecting the economic value of antibiotics. Included studies had carried
      out a cost-of-illness, cost-effectiveness, cost-utility or cost-benefit analysis.
      Exacerbation costs varied between countries and increased with the severity of
      the exacerbation. Hospitalization costs accounted for more than 45% of healthcare
      costs of exacerbations. Drug costs made up 6-21% of healthcare costs in the
      majority of studies. Cost estimates were biased due to difficulties involved in
      diagnosing and treating exacerbations, and because the patient sample studied may
      not be representative of the population of patients suffering from exacerbations.
      Although this needs to be corroborated by future research, evidence is emerging
      that second-generation antibiotics such as fluoroquinolones may have a favourable
      economic profile as compared with first-generation antibiotics. The higher
      acquisition costs of fluoroquinolones appear to be balanced by less treatment
      failure, more time between exacerbation episodes, and lower hospitalization
      costs. There is a need for prospective economic evaluations alongside clinical
      trials with a sufficient number of patients and length of follow-up period. The
      economic value of antibiotics is influenced by difficulties involved in
      diagnosing the condition, effectiveness, resistance, patient compliance with
      treatment, and treatment failure associated with antibiotics. The small number of
      economic evaluations and their methodological limitations precludes the
      recommendation of a specific antibiotic for use in the management of COPD
      exacerbations on economic grounds.

PMID- 16650976
TI  - Diagnosis of latent tuberculosis infection: the potential role of new
      technologies.
AB  - Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. TB
      control programmes need improvement in the diagnosis of latent TB infection. The
      tuberculin skin test (TST) is far from a 'gold' standard as it often gives false
      results. Interferon-gamma assays are newly available tests to detect latent TB
      infection, but they are currently not routinely used. They are based on immune
      responses to purified protein derivative (PPD) or to region of difference 1 (RD1)
      specific antigens. Assays based on RD-1 specific antigens perform better than
      both PPD based assays and TST. They correlate with TB exposure and are less
      likely to give false results in non-tuberculous mycobacterial disease, Bacille
      Calmette-Guerin (BCG) vaccination and immunosuppression. More accurate diagnosis
      of latent TB infection with RD-1 specific antigen based interferon-gamma assays
      may allow targeting of chemoprophylaxis to reduce the burden of active TB while
      decreasing wastage of health care resources due to false results associated with
      TST. However, further research and development is required to verify that new
      tests can predict the risk of later development of active TB and to make it
      feasible to perform these tests in a reproducible fashion at low cost,
      particularly in developing countries.

PMID- 16650977
TI  - Interactions between bacteria and eukaryotes via small molecules.
AB  - The interactions that occur between eukaryotes and bacteria have long been of
      interest, as knowledge of these processes could lead to the development of novel
      therapeutics and other potential applications in biotechnology. Many of these
      interactions are mediated by small molecules, which have subsequently formed the
      focus of numerous studies. An arsenal of small molecules exhibiting a wide range
      of activities has been isolated from various sources, including plants, animals
      and microorganisms. As a number of these compounds are pharmacologically active,
      there is a strong continued interest in natural product chemistry. Recent
      developments in this field have focused on two areas: evidence has been gathered
      to show that secondary metabolites are often produced by symbiotic bacteria,
      rather than by the eukaryotic host, and the importance of bacterial cell-to-cell
      signalling in bacteria-host interactions has been confirmed.

PMID- 16650978
TI  - ARX: a gene for all seasons.
AB  - The Aristaless-related homeobox gene, ARX, is an important transcription factor
      with a crucial role in forebrain, pancreas and testes development. At least fifty
      nine mutations have been described in the ARX gene in seven X-chromosome linked
      disorders involving mental retardation. Recent studies with ARX screening suggest
      that the gene is mutated in 9.5% of X-linked families with these disorders. Two
      different polyalanine expansion mutations represent 46% of all currently known
      mutations and show considerable pleiotropy. The ARX gene is emerging as one of
      the more important disease-causing genes on the X chromosome and ought to be
      considered for routine screening. Although the normal Arx protein is known to be
      a bifunctional transcriptional activator and repressor, the complete biochemical
      characterization of the normal and mutated ARX awaits further investigation. Pax4
      was identified as one of the ARX target genes, and both proteins have crucial
      functions in endocrine mouse pancreas alpha-cell and beta-cell lineage
      specification.

PMID- 16650979
TI  - The pseudoautosomal regions, SHOX and disease.
AB  - The pseudoautosomal regions represent blocks of sequence identity between the
      mammalian sex chromosomes. In humans, they reside at the ends of the X and Y
      chromosomes and encompass roughly 2.7 Mb (PAR1) and 0.33 Mb (PAR2). As a major
      asset of recently available sequence data, our view of their structural
      characteristics could be refined considerably. While PAR2 resembles the overall
      sequence composition of the X chromosome and exhibits only slightly elevated
      recombination rates, PAR1 is characterized by a significantly higher GC content
      and a completely different repeat structure. In addition, it exhibits one of the
      highest recombination frequencies throughout the entire human genome and,
      probably as a consequence of its structural features, displays a significantly
      faster rate of evolution. It therefore represents an exceptional model to explore
      the correlation between meiotic recombination and evolutionary forces such as
      gene mutation and conversion. At least twenty-nine genes lie within the human
      pseudoautosomal regions, and these genes exhibit 'autosomal' rather than sex
      specific inheritance. All genes within PAR1 escape X inactivation and are
      therefore candidates for the etiology of haploinsufficiency disorders including
      Turner syndrome (45,X). However, the only known disease gene within the
      pseudoautosomal regions is the SHORT STATURE HOMEBOX (SHOX) gene, functional loss
      of which is causally related to various short stature conditions and disturbed
      bone development. Recent analyses have furthermore revealed that the
      phosphorylation-sensitive function of SHOX is directly involved in chondrocyte
      differentiation and maturation.

PMID- 16650980
TI  - Structure of ribonuclease P--a universal ribozyme.
AB  - Ribonuclease P (RNase P) is one of only two known universal ribozymes and was one
      of the first ribozymes to be discovered. It is involved in RNA processing, in
      particular the 5' maturation of tRNA. Unlike most other natural ribozymes, it
      recognizes and cleaves its substrate in trans. RNase P is a ribonucleoprotein
      complex containing one RNA subunit and as few as one protein subunit. It has been
      shown that, in bacteria and in some archaea, the RNA subunit alone can support
      catalysis. The structure and function of bacterial RNase P RNA have been studied
      extensively, but the detailed catalytic mechanism is not yet fully understood.
      Recently, structures of one of the structural domains and of the entire RNA
      component of RNase P from two different bacteria have been described. These
      structures provide the first atomic-level information on the structural assembly
      of the RNA component, and the regions involved in substrate recognition and
      catalysis. Comparison of these structures reveals a highly conserved core that
      comprises two universally conserved structural modules. Interestingly, the same
      structural core can be found in the context of different scaffolds.

PMID- 16650981
TI  - Evolution of protein fold in the presence of functional constraints.
AB  - The functional requirement to form and maintain the active site structure
      probably exerts a strong selective pressure on a protein to adopt just one stable
      and evolutionarily conserved fold. Nonetheless, new evidence suggests the
      likelihood of protein fold being neither physically nor biologically invariant.
      Alternative folds discovered in several proteins are composed of constant and
      variable parts. The latter display context-dependent conformations and a tendency
      to form new oligomeric interfaces. In turn, oligomerisation mediates fold
      evolution without loss of protein function. Gene duplication breaks down homo
      oligomeric symmetry and relieves the pressure to maintain the local architecture
      of redundant active sites; this can lead to further structural changes.

PMID- 16650982
TI  - Evolution of transcriptional regulatory networks in microbial genomes.
AB  - Advances in sequencing and generating high-throughput expression data have
      created a situation in which it is possible to integrate comparative analysis
      with genome-wide studies of the structure and function of regulatory systems in
      model organisms. Recent studies have focused on topological properties and the
      evolution of regulatory networks. This problem can be addressed on several
      levels: evolution of binding sites upstream of orthologous or duplicated genes;
      co-evolution of transcription factors and the DNA motifs that they recognize;
      expansion, contraction and replacement of regulatory systems; the relationship
      between co-regulation and co-expression; and, finally, construction of
      evolutionary models that generate networks with realistic properties. This should
      eventually lead to the creation of a theory of regulatory evolution with a
      similar level of detail and understanding to the theory of molecular evolution of
      protein and DNA sequences.

PMID- 16650983
TI  - 3D QSAR studies of N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones: a novel
      class of antibacterial agents.
AB  - Three-dimensional QSAR studies for N-4-arylacryloylpiperazin-1-yl-phenyl
      oxazolidinones were conducted using TSAR 3.3. The in vitro activities (MICs) of
      the compounds against Staphylococcus aureus ATCC 25923 exhibited a strong
      correlation with the prediction made by the model developed in the present study.

PMID- 16650984
TI  - Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships
      of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl
      benzothiadiazine analogs containing substituents on the aromatic ring.
AB  - A series of non-nucleoside HCV NS5B polymerase inhibitors based on the N-1-benzyl
      or N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine core
      substituted in the D-ring aromatic moiety have been prepared and evaluated.
      Aromatic substituents extending from position 7 of the D-ring exhibited excellent
      potency against both genotypes 1a and 1b.

PMID- 16650985
TI  - A highly selective kappa-opioid receptor agonist with low addictive potential and
      dependence liability.
AB  - Buprenorphine analogs have been synthesized. In the studies of analgesic and
      addictive effects in mice and [(35)S]GTPgammaS binding assay in human brain
      tissue, an analog of buprenorphine where the tert-butyl is replaced by a
      cyclobutyl moiety (16) has been identified as a selective kappa-partial agonist
      which gives antinociceptive effects, but has low abuse potential. The results may
      lead to lower degrees of dysphoria than full kappa-agonists.

PMID- 16650986
TI  - Synthesis and antibacterial evaluation of ureides of Baylis-Hillman derivatives.
AB  - The synthesis of several 1-(2-cyano-3-aryl-allyl)-3-aryl-urea(thiourea)
      constructed from the reaction between allylamines generated from Baylis-Hillman
      acetates and substituted isocyanates and isothiocyanates has been described.
      Further, their cyclization in the presence of a base led to the formation of 5
      arylmethyl-4-imino-3-aryl-3,4-dihydro-1H-pyrimidin-2-ones. All compounds were
      tested for their antibacterial activity. Few of the compounds showed superior
      activity or were equipotent to the standard antibacterial agents.

PMID- 16650987
TI  - Efforts toward oral bioavailability in factor VIIa inhibitors.
AB  - Efforts toward developing orally bioavailable factor VIIa inhibitors starting
      from parenteral lead compound 1 are described. SAR resulted in improved
      physicochemical properties, leading to enhanced oral absorption in rat.

PMID- 16650988
TI  - Facile synthesis and application of uniformly 13C, 15N-labeled phosphotyrosine
      for ligand binding studies.
AB  - The first synthesis of [U-13C, 15N] labeled phosphotyrosine is described.
      Preliminary studies toward the binding of phosphotyrosine to an SH2 domain have
      been performed by means of heteronuclear NMR.

PMID- 16650989
TI  - SAR studies of 2-methoxyestradiol and development of its analogs as probes of
      anti-tumor mechanisms.
AB  - The major estrogen metabolite 2-methoxyestradiol (2ME) has been shown to target
      tumor cells without severe side effects and is currently being evaluated in
      clinical trials for several types of cancer. Despite its promise for use in
      clinical setting, the mechanism(s) by which 2ME exerts its anti-tumor activity is
      not clearly defined at this time. Employing organic chemistry tools, we
      synthesized 2ME analogs with which 2ME affinity column was prepared, enabling us
      to detect a protein that selectively interacts with 2ME. This 2ME analog will be
      useful as a probe to identify the biological target(s) of 2ME and study their
      functions in tumor cells.

PMID- 16650990
TI  - Regiospecific one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives in the
      solid state under microwave irradiations.
AB  - Electron rich 6-[(dimethylamino)methylene]amino uracil 1, undergoes [4+2]
      cycloaddition reactions with various in situ generated glyoxylate imine and imine
      oxides 6 to provide novel pyrimido[4,5-d]pyrimidine derivatives of biological
      significance, after elimination of dimethylamine from the (1:1) cycloadducts and
      oxidative aromatisation. This procedure provides a convenient method for the
      direct synthesis of pyrimido[4,5-d]pyrimidines in excellent yields when carried
      out in the solid state and under microwave irradiations.

PMID- 16650991
TI  - Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential
      treatment for Type 1 diabetes.
AB  - Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti
      inflammatory agent that protects beta-cells from Th1 cytokine-induced dysfunction
      and reduces the onset of Type 1 diabetes in non-obese diabetic (NOD) mice. Due to
      its low potency, poor oral bioavailability, and short half-life, the widespread
      clinical utility of LSF may be limited. Our goal has been to develop new agents
      based on the LSF structural motif that resolve the potency and pharmacokinetic
      liabilities of LSF. In this study, we have generated a focused library of LSF
      analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while
      substituting a variety of nitrogen-containing heterocyclic substructures for the
      xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7
      deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were
      evaluated in a pancreatic beta-cell line for the effects on apoptosis protection
      and insulin release. The metabolic stability of selected compounds was also
      tested.

PMID- 16650992
TI  - The neuroprotective activity of GPE tripeptide analogues does not correlate with
      glutamate receptor binding affinity.
AB  - The influence of several modifications on the GPE tripeptide structure upon the
      binding to GluRs and on their neuroprotective effects has been studied. The
      results indicated that the prevention of neuronal death showed by GPE and some
      analogues is not directly related to their affinity at glutamate receptors.

PMID- 16650993
TI  - The diagnostic impact of contrast-enhanced MRI in management of breast disease.
AB  - For effective use, the diagnostic impact of contrast-enhanced breast MRI (CE MRI)
      needs to be quantified. This is a retrospective study of 441 women who have
      undergone CE MRI of the breast from 1 July 1997 to 25 March 2002. Indications for
      CE MRI studies were diagnostic in 176, monitoring chemotherapy in 126 and study
      of MRI screening for breast cancer (MARIBS) cases in 139. CE MRI results were
      confusing or incorrect in 6% of the diagnostic group, 13% of the chemotherapy
      group and 9% of the MARIBS group. In 18 of 38 of these cases CE MRI stimulated
      further tests to clarify a clinical query. CE MRI resulted in an increase in
      confidence or change in clinical plan in 46% of the diagnostic group, 72% of the
      chemotherapy group and 80% of the MARIBS group. In 44 of 283 of these, CE MRI
      caused a beneficial change in the clinical plan based on conventional radiology.
      CE MRI results in a positive diagnostic impact above conventional imaging in a
      clinically important proportion of patients, but gives some false calls in a
      smaller proportion (8.6%).

PMID- 16650994
TI  - Tiam1 takes PARt in cell polarity.
AB  - Cell polarity is an essential requirement for the proper tissue development of
      complex organisms. This is underscored by in vivo studies showing that loss of
      cell polarity contributes to the formation and progression of tumours.
      Evolutionary conserved multiprotein complexes, such as the Par3-Par6-aPKC or, in
      short, the Par polarity complex, regulate the establishment of cell polarity. The
      small Rho GTPases CDC42 and Rac control the activation of the Par polarity
      complex. Evidence now implicates the Rac activator Tiam1 as a crucial component
      of the Par complex in regulating neuronal (axonal) and epithelial (apical-basal)
      polarity. Our current knowledge places Tiam1 at the centre of a pivotal
      biological process, the establishment and maintenance of cell polarity, and
      suggests that deregulation of the Tiam1-Par complex contributes to
      tumourigenicity.

PMID- 16650995
TI  - 2D QSAR of PPARgamma agonist binding and transactivation.
AB  - Multilinear QSAR models are developed for the largest and most diverse set of
      PPARgamma agonists treated hitherto. Binding of these small molecules to the
      human nuclear receptor PPARgamma is described by models that are built on simple
      2D molecular descriptors and nevertheless are of good quality and predictive
      power (e.g., 144 compounds, 10 descriptors, r2=0.79, r2(cv)=0.76). The models
      presented are thoroughly validated by crossvalidation, randomization experiments,
      bootstrapping, and training set/test set partitioning. They may therefore be
      helpful in the design of new antidiabetic drug candidates. For gene
      transactivation, the functional activity of the agonists, a corresponding model
      for a similarly diverse compound set is of somewhat lower statistical quality.

PMID- 16650996
TI  - Novel 2-substituted nitronyl nitroxides as free radical scavengers: synthesis,
      biological evaluation and structure-activity relationship.
AB  - To develop more potent small molecules with enhanced free radical scavenger
      properties, we designed and synthesized a series of nitronyl nitroxide
      derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced
      vascorelaxation assay. Further chemical modification based on this scaffold
      provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s.
      The newly synthesized compounds 6a-s possess improved radical scavenger's
      activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of
      the most potent compounds in terms of NO, H(2)O(2), and OH scavenging ability. 2
      Substitued phenylnitronyl nitroxides had a higher radical scavenging activity
      with the electron-donating group (EDG). In contrast, the introduction of electron
      withdrawing group (EWG) to the aromatic ring led to a dramatic decrease in its
      radical scavenging activity. These results suggest that the electron-donating
      group (EDG) of the aromatic ring may be an important factor influencing the
      radical scavenging behavior of these compounds, and the potency of free radical
      scavenging activity largely depended on the position and electronic properties of
      the phenyl ring substituents. The enhanced radical scavenging capacities of the
      novel 2-substituted nitronyl nitroxides may be potential drug leads against the
      deleterious action of ROS (reactive oxygen species)/RNS (reactive nitrogen
      species).

PMID- 16650997
TI  - Development of affinity chromatography using a bioactive peptide as a ligand.
AB  - By repeatedly introducing hydrophilic polyethylene glycol (PEG) spacer (2) onto
      affinity resin bearing a bioactive peptide (1/2 secretory leukocyte protease
      inhibitor, 1/2SLPI) as a ligand, the adsorption of nonspecific binding proteins
      was effectively reduced and the purification efficacy of elastase, which is one
      of the target molecules for 1/2SLPI, from a protein mixture was improved.
      Moreover, using this resin, we also successfully detected L-plastin, as an
      endogenous target molecule for SLPI, from HL-60 cell lysate.

PMID- 16650998
TI  - Synthesis of 7-chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4
      benzothiazines as antimicrobial agents.
AB  - 7-Chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines have
      been synthesized by 2-amino-5-fluoro/5-trifluoromethyl/5-chloro-3-trifluoromethyl
      benzenethiols condensed with beta-diketone/beta-ketoesters in the presence of
      DMSO involving oxidative cyclization. Pharmacological activities have also been
      included.

PMID- 16650999
TI  - QSAR modeling of the inhibition of glycogen synthase kinase-3.
AB  - Quantitative structure-activity relationship (QSAR) models of the biological
      activity (pIC50) of 277 inhibitors of Glycogen Synthase Kinase-3 (GSK-3) are
      developed using geometrical, topological, quantum mechanical, and electronic
      descriptors calculated by CODESSA PRO. The linear (multilinear regression) and
      nonlinear (artificial neural network) models obtained link the structures to
      their reported activity pIC50. The results are discussed in the light of the main
      factors that influence the inhibitory activity of the GSK-3 enzyme.

PMID- 16651000
TI  - Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing
      40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.
AB  - Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were
      synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor
      bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o
      carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3
      hydroxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 8, are B40 congeners with
      different lipophilicities, each less than their B80 congener, copper (II) meso
      5,10,15,20-tetrakis[m-(3,5-di-o-carboranylmethoxybenzyloxy)phenyl]porphyrin, 18.
      Two days after the last of a series of i.p. injections in BALB/c mice bearing EMT
      6 mammary tumors, a dose of 185 mg/kg 6 (54 mg/kg B) delivered over 3.5 times the
      concentration of boron to tumor (169 microg/g B) than did 118 mg/kg 8 (36 mg/kg
      B), which delivered 35 microg/g B, or 87 mg/kg 18 (30 mg/kg B), which delivered
      46 microg/g B. The tumor-to-blood and tumor-to-brain boron concentration ratios
      at that time for all three porphyrins exceeded 80:1. Two days after the last
      injection, there resulted moderate thrombocytopenia that essentially disappeared
      two days later from 6 and 18, and mild leukocytosis from 6, 8, and 18, all of
      which were clinically inconsequential. Thus, 6 may rank among the most clinically
      promising carboranyl porphyrins ever made to deliver 10B to tumors for boron
      neutron-capture therapy (BNCT) that has also been tested for its toxicity in
      vivo.

PMID- 16651001
TI  - Exploration of orally available calpain inhibitors. Part 3: Dipeptidyl alpha
      ketoamide derivatives containing pyridine moiety.
AB  - Calpain-mediated proteolysis has been implicated as a major process in neuronal
      cell death including retinal neurological degeneration. The previously reported
      calpain inhibitor SJA6017 (1) showed oral efficacy in a retinal pharmacological
      model, but its oral bioavailability was low due to the metabolic lability and low
      water-solubility. The purpose of present study was to identify good orally
      bioavailable calpain inhibitors. A series of water-soluble dipeptidyl alpha
      ketoamides containing a pyridine moiety at P3 were designed, synthesized, and
      evaluated for their oral bioavailability and retinal penetration. Introduction of
      a pyridineethanol moiety provided the potent alpha-ketoamide inhibitor 8 with
      good oral bioavailability. Compound 8 showed about 12-fold higher retinal AUC
      than 1.

PMID- 16651002
TI  - Synthesis and pharmacological activities of xanthone derivatives as alpha
      glucosidase inhibitors.
AB  - Considerable interest has been attracted in xanthone and its derivatives because
      of their large variety of pharmacological activities. In this project, a series
      of hydroxylxanthones and their acetoxy and alkoxy derivatives were synthesized
      and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure
      activity correlation. The results indicated that these xanthone derivatives were
      capable of inhibiting in vitro alpha-glucosidase with moderate to good
      activities. Among them, polyhydroxylxanthones exhibited the highest activities
      and thus may be exploitable as a lead compound for the development of potent
      alpha-glucosidase inhibitors.

PMID- 16651003
TI  - Early and transient alteration of adenosine A2A receptor signaling in a mouse
      model of Huntington disease.
AB  - Huntington Disease (HD) is characterized by choreic involuntary movements and
      striatal vulnerability. A2A receptors expressed on GABAergic striatal neurons
      have been suggested to play a pathogenetic role. Previous data demonstrated the
      presence of an aberrant alteration of A2A receptor-dependent adenylyl cyclase in
      an in vitro model of the disease (striatal cells expressing mutant huntingtin)
      and in peripheral circulating cells of HD patients. Here, we investigated whether
      this dysfunction is present in the R6/2 HD transgenic mouse model, by analyzing
      striatal A2A receptor-binding and adenylyl cyclase activity at different
      developmental stages in comparison with age-matched wild type animals. A
      transient increase in A2A receptor density (Bmax) and A2A receptor-dependent cAMP
      production at early presymptomatic ages (7-14 postnatal days) was found. Both
      alterations normalized to control values starting from postnatal day 21. In
      contrast, A2A receptor mRNA, as detected by real time PCR, dramatically decreased
      starting from PND21 until late symptomatic stages (12 weeks of age). The
      discrepancy between A2A receptor expression and density suggests compensatory
      mechanisms. These data, reproducing ex vivo the previous observations in vitro,
      support the hypothesis that an alteration of A2A receptor signaling is present in
      HD and might represent an interesting target for neuroprotective therapies.

PMID- 16651004
TI  - Antihypertensive effect of ragaglitazar: a novel PPARalpha and gamma dual
      activator.
AB  - Ragaglitazar is a novel and potent dual peroxisome proliferators activated
      receptor (PPAR) alpha and gamma activator. The aim of this study is to
      investigate the effect of ragaglitazar on blood pressure and endothelial function
      in insulin resistant animal model and non-insulin resistant hypertensive models.
      The effects ragaglitazar were tested in Zucker fa/fa, spontaneously hypertensive
      rats (SHR), 2 kidney 1clip rat (2K1C) and Wistar Kyoto rats (WKY). Pioglitazone
      was taken as a comparative standard. Ragaglitazar showed significant reduction
      (P<0.001) of systolic blood pressure (SBP) in insulin resistant fa/fa rats, with
      concomitant reduction in plasma triglycerides (TG) and insulin levels while
      pioglitazone (10 mg kg(-1)) showed significant (P<0.05) but comparatively less
      reduction. Ragaglitazar in contrast to pioglitazone showed significant reduction
      (P<0.05) of SBP in SHR, 2K1C while the same dose did not have any effect on
      normotensive WKY. Ragaglitazar also showed significant improvement in
      acetylcholine-induced relaxation in isolated aorta of Zucker fa/fa, SHR, 2K1C and
      also potentiated the insulin-induced vasorelaxation in Zucker fa/fa rats. These
      findings summarize that ragaglitazar shows significant reduction of BP and
      improvement in endothelial function not only in insulin resistant but also in non
      insulin resistant hypertensive models where standard thiazolidinediones are
      ineffective. These data indicates that dual PPARalpha and gamma activator
      ragaglitazar can be beneficial for the treatment of hypertension and vascular
      disease commonly associated with type 2 diabetes.

PMID- 16651006
TI  - Attempts to rationalize protein crystallization using relative crystallizability.
AB  - Protein crystal growth (PCG) remains the bottleneck of crystallography despite
      many decades of study. The nucleation zone in the two-dimensional-phase diagram
      has been used to evaluate the relative crystallizability of proteins, which is
      expressed as a percentage over the phase area delineated by experimental protein
      and precipitating agent concentration ranges. For protein-salts which are subject
      to a direct temperature effect on solubility, as represented by Egg Lysozyme, a
      decrease in temperature augments the nucleation zone percentage whereas for those
      with retrograde solubility as a function of temperature, for example fructose-1,6
      bisphosphatase in the presence and absence of AMP, an increase in temperature can
      significantly enhance the relative crystallizability. These results have been
      confirmed by the number of "hits" using PEGs as precipitating agents in Sparse
      Matrix Screen experiments for different proteins and are in excellent agreement
      with the relative crystallizability. The relationship between solubility
      dependence, relative crystallizability and crystallization success, has been
      evidenced. Such crystallizability can become a guide to identify efficient
      crystallization regions, providing a rational approach to PCG and structural
      biology.

PMID- 16651007
TI  - Reading cinnamon activates olfactory brain regions.
AB  - Some words immediately and automatically remind us of odours, smells and scents,
      whereas other language items do not evoke such associations. This study
      investigated, for the first time, the abstract linking of linguistic and odour
      information using modern neuroimaging techniques (functional MRI). Subjects
      passively read odour-related words ('garlic', 'cinnamon', 'jasmine') and neutral
      language items. The odour-related terms elicited activation in the primary
      olfactory cortex, which include the piriform cortex and the amygdala. Our results
      suggest the activation of widely distributed cortical cell assemblies in the
      processing of olfactory words. These distributed neuron populations extend into
      language areas but also reach some parts of the olfactory system. These
      distributed neural systems may be the basis of the processing of language
      elements, their related conceptual and semantic information and the associated
      sensory information.

PMID- 16651008
TI  - Reliability of MRI-derived measurements of human cerebral cortical thickness: the
      effects of field strength, scanner upgrade and manufacturer.
AB  - In vivo MRI-derived measurements of human cerebral cortex thickness are providing
      novel insights into normal and abnormal neuroanatomy, but little is known about
      their reliability. We investigated how the reliability of cortical thickness
      measurements is affected by MRI instrument-related factors, including scanner
      field strength, manufacturer, upgrade and pulse sequence. Several data processing
      factors were also studied. Two test-retest data sets were analyzed: 1) 15 healthy
      older subjects scanned four times at 2-week intervals on three scanners; 2) 5
      subjects scanned before and after a major scanner upgrade. Within-scanner
      variability of global cortical thickness measurements was <0.03 mm, and the point
      wise standard deviation of measurement error was approximately 0.12 mm.
      Variability was 0.15 mm and 0.17 mm in average, respectively, for cross-scanner
      (Siemens/GE) and cross-field strength (1.5 T/3 T) comparisons. Scanner upgrade
      did not increase variability nor introduce bias. Measurements across field
      strength, however, were slightly biased (thicker at 3 T). The number of (single
      vs. multiple averaged) acquisitions had a negligible effect on reliability, but
      the use of a different pulse sequence had a larger impact, as did different
      parameters employed in data processing. Sample size estimates indicate that
      regional cortical thickness difference of 0.2 mm between two different groups
      could be identified with as few as 7 subjects per group, and a difference of 0.1
      mm could be detected with 26 subjects per group. These results demonstrate that
      MRI-derived cortical thickness measures are highly reliable when MRI instrument
      and data processing factors are controlled but that it is important to consider
      these factors in the design of multi-site or longitudinal studies, such as
      clinical drug trials.

PMID- 16651009
TI  - Dissociation of neural responses and skin conductance reactions during fear
      conditioning with and without awareness of stimulus contingencies.
AB  - This study investigates the effect of awareness of stimulus contingencies on BOLD
      responses within the amygdala, the orbitofrontal, and the occipital cortex, and
      on differential skin conductance responses (SCRs) during fear conditioning. Of
      two geometric figures, the paired conditioned stimulus (CS+) predicted an
      electrical stimulus (unconditioned stimulus = UCS), whereas the unpaired
      conditioned stimulus (CS-) was not followed by the UCS. Awareness of stimulus
      contingencies was manipulated experimentally, creating an aware and an unaware
      group: a distracter figure and a working memory task were introduced to conceal
      the stimulus contingencies of the conditioning paradigm, hence preventing
      contingency detection in the unaware group. The aware group was informed
      beforehand about the relation between CS+, CS-, and UCS. Differential SCRs were
      only obtained in the aware but not in the unaware group. Conversely, we observed
      enhanced responses of the amygdala, the orbitofrontal, and the occipital cortex
      to the CS+ in the unaware group only. Thus, we found a dissociation of SCR
      differentiation and the activation of a neural fear network depending on the
      presence or absence of awareness. These results support a model of fear
      conditioning that distinguishes between a more cognitive level of learning,
      reflected in contingency awareness and differential SCRs, and the awareness
      independent activation of a fear network.

PMID- 16651010
TI  - Using a white matter reference to remove the dependency of global signal on
      experimental conditions in SPECT analyses.
AB  - Proportional scaling models are often used in functional imaging studies to
      remove confounding of local signals by global effects. It is generally assumed
      that global effects are uncorrelated with experimental conditions. However, when
      the global effect is estimated by the global signal, defined as the intracerebral
      average, incorrect inference may result from the dependency of the global signal
      on preexisting conditions or experimental manipulations. In this paper, we
      propose a simple alternative method of estimating the global effect to be used in
      a proportional scaling model. Specifically, by defining the global signal with
      reference strictly to a white matter region within the centrum semiovale, the
      dependency is removed in experiments where white matter is unaffected by the
      disease effect or experimental treatments. The increase in the ability to detect
      changes in regional blood flow is demonstrated in a SPECT study of healthy and
      ill Gulf War veterans in whom it is suspected that brain abnormalities influence
      the traditional calculation of the global signal. Controlling for the global
      effect, ill veterans have significantly lower intracerebral averages than healthy
      controls (P = 0.0038), evidence that choice of global signal has an impact on
      inference. Scaling by the modified global signal proposed here results in an
      increase in sensitivity leading to the identification of several regions in the
      insula and frontal cortex where ill veterans have significantly lower SPECT
      emissions. Scaling by the traditional global signal results in the loss of
      sensitivity to detect these regional differences. Advantages of this alternative
      method are its computational simplicity and its ability to be easily integrated
      into existing analysis frameworks such as SPM.

PMID- 16651011
TI  - Mechanisms for detecting auditory temporal and spectral deviations operate over
      similar time windows but are divided differently between the two hemispheres.
AB  - In order to keep track of potentially relevant information in the acoustic
      environment, the human brain processes sounds to a high extent even when they are
      not attended: it extracts basic features, encodes regularities, and detects
      deviances. Here, we deliver evidence that the initial 300 ms of a sound
      contribute more to this preattentive processing than the sound's later parts. We
      directly compared the influence of the temporal distance relative to sound onset
      on the processing of the sound's duration and frequency information. The mismatch
      negativity (MMN), an event-related potential indicator for preattentive feature
      encoding and deviance detection, was measured for infrequent duration deviants
      and frequency modulation deviants. The onset of either deviancy was at 100, 200,
      300, or 400 ms relative to sound onset. MMN was only elicited for deviations
      occurring within the first 300 ms after sound onset for both types of deviants.
      Its neural sources were localized in supra-temporal cortices with source current
      density analyses (SCD) and variable resolution electromagnetic tomography
      (VARETA), revealing a right-hemispheric preponderance for frequency modulations
      but not for duration shortenings. This suggests that preattentive deviance
      detection is based upon partly diverging functional memory registers for temporal
      and dynamic spectral information. The influence of temporal distance on MMN in
      both conditions supports the view that temporal and spectral sound properties are
      integrated into an auditory object representation prior to preattentive deviance
      detection. Importantly, the decline of MMN to unattended sounds with larger
      temporal distance suggests that parts beyond 300 ms are less important for
      preattentive auditory object representation.

PMID- 16651012
TI  - An fMRI task battery for assessing hemispheric language dominance in children.
AB  - Hemispheric dominance for language is an important issue in functional
      neuroimaging, particularly driven by efforts to overcome the need for the
      invasive Wada test, which is all the more pressing in children. Here, we aimed at
      developing new paradigms for functional magnetic resonance imaging (fMRI) for
      assessment of language dominance that can be used in younger children and allow
      for performance monitoring. Two new tasks (letter and animal task) were developed
      and compared to two reference tasks (synonyms and verb generation task) from the
      literature. Overall, 23 healthy children participated (13 boys, 10 girls, 10.2 +/
      2.5 years, range 6.1-15.3 years). Analysis was done using statistical
      nonparametrical mapping (SnPM2) on SPM2. Both reference tasks show activation in
      a number of left-frontal brain regions. The letter task induced a very localized
      activation in the left hemisphere's Broca's region, while not activating other
      frontal brain regions. Lateralization (as assessed in different anatomically and
      functionally defined regions) was consistent and strong. The animal task failed
      to activate frontal brain regions and was not suitable for assessing language
      dominance in children in this form. We conclude that while both reference tasks
      are useful for determining language dominance, they coactivate a number of task
      related frontal areas not directly involved in language processing. Additionally,
      one task is not applicable in young children while the other does not allow
      performance monitoring. The letter task allows to selectively activate language
      areas in the dominant hemisphere and is applicable even in the very lowest age
      group amenable to fMRI investigations while still allowing performance
      monitoring. It may thus be a useful tool in assessing normal and pathological
      language organization.

PMID- 16651013
TI  - Vagus nerve stimulation and cognition.
AB  - Vagus nerve stimulation (VNS) has been developed as an add-on treatment for
      patients with refractory epilepsy. Based on the clinical observation of improved
      cognition in many epilepsy patients who received VNS, we reviewed the recent
      literature for evidence concerning the cognitive effects of this treatment. From
      most of these studies it seems that, with currently used stimulation parameters,
      the effects on memory are only of theoretical importance. However, some animal
      studies suggest positive effects on specific modalities of memory function. In
      studies in epilepsy patients, there is no evidence of adverse effects on
      cognition but clear-cut positive effects cannot be expected either. Preliminary
      results of VNS in the treatment of diseases associated with cognitive decline
      such as Alzheimer's disease seem promising but need to be further investigated.

PMID- 16651014
TI  - Increased incidence of Parkinson disease among relatives of patients with Gaucher
      disease.
AB  - In a previous study of 99 Ashkenazi Jewish patients with Parkinson disease from
      Israel who were tested for the six most common mutations for Gaucher disease,
      31.3% had at least one Gaucher disease mutation, implying that carrier status per
      se my be a risk for Parkinson disease. The purpose of this survey was to
      ascertain the presence of Parkinson disease among Ashkenazi Jewish obligate
      carriers of Gaucher disease relative to its incidence in a comparable cohort of
      Ashkenazi Jews who are putatively non-carriers. There was no statistically
      significant difference in gender or age between the groups (n>100). Among
      patients, 27.3% reported having a relative with Parkinson disease while among the
      controls there was a reported 12.3% which was statistically significant (P=0.05).
      While based completely on subjective reports in a paper-base questionnaire, the
      results of this survey implicate a high rate of Parkinson disease among
      individuals with Gaucher disease mutations.

PMID- 16651015
TI  - Cloning, characterization and expression analysis of two Tetraodon nigroviridis
      interleukin-16 isoform genes.
AB  - Interleukin-16 (IL-16) is an important pro-inflammatory cytokine that functions
      as a chemoattractant factor and is well characterized in human and other mammals,
      but is largely unknown in fish. In the present study, two isoforms of pro-IL-16
      homologues were cloned and characterized from pufferfish Tetraodon nigroviridis.
      The full-length T. nigroviridis pro-IL-16 isoform 1 cDNA exhibits 2453 bp in size
      including 291 bp 5'UTR (untranslated region), 1704 bp ORF (open reading frame)
      and 458 bp 3'UTR, while pro-IL-16 isoform 2 cDNA exhibits a 3801 bp ORF and a 458
      bp 3'UTR. Bioinformatics analysis demonstrated that the pro-IL-16 isoform 1 with
      a predicted mass of 60.6 kDa contained two PDZ (postsynaptic density/disc
      large/zona occludens-1) domains, whereas the 138.2 kDa pro-IL-16 isoform 2 had
      two additional PDZ domains in its N-terminal extension. RT-PCR results revealed
      that ,almost in all examined organs and tissues, the mRNA of both pro-IL-16
      isoforms can be detected, except in intestine and gill, where the isoform 2 mRNA
      is absent. The two putative precursor proteins showed 30.0-33.0% identity to
      various mammalian and avian homologues. This is the first report of such genes in
      teleostean fish and we hope the molecular characterization of these two pro-IL-16
      isoforms will provide insights into the study of both evolution of IL-16
      precursor proteins and the immune system as a whole.

PMID- 16651016
TI  - Age-associated changes of insulin action on the hydrolysis of diacylglycerol
      generated from phosphatidic acid.
AB  - Age-related changes in insulin action on diacylglycerol (DAG) degradation was
      studied in rat cerebral cortex synaptosomes. The generation of monoacylglycerol
      (MAG) and water soluble products (WSP, glycerol plus glycerol-3-phosphate) from
      DAG was studied in cerebral cortex (CC) synaptosomes from adult (4-month-old) and
      aged (28-month-old) rats. Additionally, the effect of porcine insulin and
      tyrosine phosphorylation was evaluated in the same group of animals. In this
      study we demonstrate that the age-related increase in WSP generation was
      accompanied by unmodified MAG levels. In the presence of diacylglycerol lipase
      (DAG lipase) inhibitor, RHC-80267, a lower inhibitory effect on MAG production
      was observed in CC synaptosomes from aged rats with respect to that in adult
      membranes. Under these experimental conditions, WSP formation was only diminished
      in aged membranes. Insulin stimulated MAG and WSP formation at long incubation
      times (30 min) in adult animals, while it had an inhibitory effect in aged
      animals. Insulin plus vanadate (as tyrosine-phosphatase inhibitor) inhibited MAG
      production at short incubation times whereas the same effect was observed in aged
      animals at long times of incubation. WSP formation was stimulated by insulin plus
      vanadate both in adult and aged animals at 30 min of incubation. Our results show
      that insulin differentially modulates MAG and WSP production from exogenous PA in
      CC synaptosomes from aged rats compared with adult rats.

PMID- 16651017
TI  - Parathyroid adenocarcinoma in a nephropathic Persian cat.
AB  - This report describes an uncommon clinical case of cystic parathyroid
      adenocarcinoma. A 17-year-old male Persian cat was presented for evaluation of a
      ventral cervical mass. The cat was inappetent and showed weight loss, polydipsia
      and vomiting. Serum biochemistry and urinalysis revealed moderate hypercalcaemia,
      a mild increase of creatinine, isosthenuria and proteinuria. Sodium dodecyl
      sulphate-agarose gel electrophoresis showed a mixed tubular proteinuric pattern,
      in accordance with histological examination that revealed interstitial nephritis
      and glomerulonephritis. Diagnosis of parathyroid carcinoma was based on
      histopathological findings.

PMID- 16651018
TI  - Acute brucellosis: presentation, diagnosis, and treatment of 144 cases.
AB  - OBJECTIVES: Brucellosis, whether in an endemic region or not, remains a
      diagnostic puzzle due to occasional misleading unusual presentations and non
      specific symptoms. Presented herein is our 14-year experience with acute
      brucellosis at Sparta General Hospital, Lakonia, Greece. METHODS: A case series
      of 144 patients admitted to the internal medicine, pediatrics, and urology
      departments, through evaluation of history, occupational data, serological tests,
      cultures of blood and other body fluids, and imaging studies. Patients were
      treated with a 21-day course of intramuscular streptomycin and a prolonged two
      month course of doxycycline with a six-month follow-up. RESULTS: Infected
      patients had a relevant occupational history in fewer than 20% of cases. Clinical
      manifestations included non-specific symptoms (fever, malaise, sweats,
      arthralgias, lower back pain, headache), findings such as splenomegaly (51%),
      osteoarticular involvement (42%), cervical lymphadenitis (31%), hepatomegaly
      (25%), genitourinary involvement (13% of men), cholecystitis (2%), breast abscess
      (0.7%), and acute abdomen (0.7%). Ninety-five percent of the patients had a
      serological titer > or =1/160 with culture-proven brucellosis. Overall, 82% of
      blood cultures and 100% of other body fluid cultures (synovial, bile) were
      positive. Ninety-seven percent of the patients were cured. Relapse in the follow
      up period was observed in four patients who had not complied with treatment.
      CONCLUSIONS: Brucellosis is an infection with multiple presentations, and whether
      in an endemic region or not, a thorough history of exposure and clinical
      suspicion are required since thresholds in serological evaluation may lead to
      misdiagnosis and withholding of adequate treatment.

PMID- 16651019
TI  - Prosodic phrasing is central to language comprehension.
AB  - Words, like musical notes, are grouped together into phrases by their rhythmic
      and durational properties as well as their tonal pitch. This 'prosodic phrasing'
      affects the understanding of sentences. Many processing studies of prosody have
      investigated sentences with a single, grammatically required prosodic boundary,
      which might be interpreted strictly locally, as a signal to end the current
      syntactic unit. Recent results suggest, however, that the global pattern of
      prosodic phrasing is what matters in sentence comprehension, not just the
      occurrence or size of a single local boundary. In this article we claim that the
      impact of prosodic boundaries depends on the other prosodic choices a speaker has
      made. We speculate that prosody serves to hold distinct linguistic
      representations together in memory.

PMID- 16651020
TI  - Microbial genomics for the improvement of natural product discovery.
AB  - The quest for the discovery of novel natural products has entered a new chapter
      with the enormous wealth of genetic data that is now available. This information
      has been exploited by using whole-genome sequence mining to uncover cryptic
      pathways, or biosynthetic pathways for previously undetected metabolites.
      Alternatively, using known paradigms for secondary metabolite biosynthesis,
      genetic information has been 'fished out' of DNA libraries resulting in the
      discovery of new natural products and isolation of gene clusters for known
      metabolites. Novel natural products have been discovered by expressing genetic
      data from uncultured organisms or difficult-to-manipulate strains in heterologous
      hosts. Furthermore, improvements in heterologous expression have not only helped
      to identify gene clusters but have also made it easier to manipulate these genes
      in order to generate new compounds. Finally, and perhaps the most crucial aspect
      of the efficient and prosperous use of the abundance of genetic information,
      novel enzyme chemistry continues to be discovered, which has aided our
      understanding of how natural products are biosynthesized de novo, and enabled us
      to rework the current paradigms for natural product biosynthesis.

PMID- 16651021
TI  - Serum amyloid A (SAA)-induced remodeling of CSF-HDL.
AB  - Inflammation is a risk factor for Alzheimer's disease. Serum amyloid A (SAA) is
      an acute phase protein that dissociates apolipoprotein AI (apoAI) from plasma
      HDL. In cerebrospinal fluid (CSF), the SAA concentration is much higher in
      subjects with Alzheimer's disease than in controls. CSF-HDL is rich in apoE,
      which plays an important role as a ligand for lipoprotein receptors in the
      central nervous system (CNS). To clarify whether SAA dissociates apoE from CSF
      HDL, we added recombinant SAA to CSF and determined the apoE distribution in the
      CSF using native two-dimensional gel electrophoresis. We found that SAA
      dissociated apoE from CSF-HDL in a dose-dependent manner. This effect was more
      evident in apoE4 carriers than in apoE3 or apoE2 carriers. After a 24-h
      incubation at 37 degrees C, SAA continuously dissociated apoE from CSF-HDL.
      Amyloid beta (Abeta) fragments (1-42) were bound to large CSF-HDL but not to apoE
      dissociated by SAA. In conclusion, SAA dissociates apoE from CSF-HDL. We
      postulate that inflammation in the CNS may impair Abeta clearance due to the loss
      of apoE from CSF-HDL.

PMID- 16651022
TI  - Oxidative stress and arachidonic acid mobilization.
AB  - Reactive oxygen species are known to contribute to tissue damage during injury
      and inflammation. However, these species can also be sensed by the cells and
      trigger intracellular signaling cascades. This review examines recent evidence on
      the involvement of reactive oxygen species in lipid signaling. Attention is
      focused on activation of phospholipase A2s, enzymes whose action on membrane
      phospholipids can also render molecules with opposite effects on cells. The
      participation of Ca2+-dependent and Ca2+-independent phospholipase A2s in
      arachidonic acid mobilization from phospholipids is discussed, with particular
      attention to the interplay between cytosolic and secreted Ca2+-dependent forms.
      The involvement of alternative routes for arachidonic acid mobilization under
      oxidative stress is also considered.

PMID- 16651023
TI  - Modulations of interlimb and intralimb cutaneous reflexes during simultaneous arm
      and leg cycling in humans.
AB  - OBJECTIVE: We investigated to what extent intralimb and interlimb cutaneous
      reflexes are altered while simultaneously performing arm and leg cycling (AL
      cycling) under different kinematic and postural conditions. METHODS: Eleven
      subjects performed AL cycling under conditions in which the arm and leg crank
      ipsilateral to the stimulation side were moved synchronously (in-phase cycling)
      or asynchronously (anti-phase cycling) while sitting or standing. Cutaneous
      reflexes following superficial radial or superficial peroneal nerve stimulation
      (2.0-2.5 times radiating threshold, 5 pulses at 333 Hz) were recorded at 4
      different pedal positions from 12 muscles in the upper and lower limbs. Cutaneous
      reflexes with a peak latency of 80-120 ms were then analyzed. RESULTS: The
      magnitude of interlimb and intralimb cutaneous reflexes in the arm and leg
      muscles was significantly modulated depending on the crank position for the
      relevant limb (phase-dependent modulation). A significant correlation between the
      magnitude of the cutaneous reflex and background EMG was observed in the majority
      of muscles during static contraction, but not during AL cycling (task-dependent
      modulation). No significant difference was found in comparisons of the magnitude
      of intralimb and interlimb cutaneous reflexes obtained during in- and anti-phase
      AL cycling. Qualitatively, the same results were obtained during AL cycling while
      sitting or standing. In addition, the modulation of cutaneous reflexes in arm
      muscles was identical among in-phase, anti-phase and isolated arm cycling.
      Results were the same for leg muscles. CONCLUSIONS: Cutaneous reflexes in arm
      muscles are little influenced by rhythmic movement of the legs and vice versa
      during AL cycling. It is likely that neural components that control interlimb
      reflexes are loosely coupled during AL cycling while sitting or standing.
      SIGNIFICANCE: Our results provide a better understanding of the coordination
      between the upper and lower limbs during rhythmic movement.

PMID- 16651024
TI  - Chemosensory event-related potentials in relation to side of stimulation, age,
      sex, and stimulus concentration.
AB  - OBJECTIVE: For chemosensory event-related potentials (ERP) significant effects of
      age and sex have been demonstrated. The aim of the present study was to assess
      the effects of stimulus concentration, side of stimulation, and sex on the
      topographical distribution of chemosensory ERP in a large group of subjects
      stratified for different age groups. In addition, psychophysical measures of both
      olfactory and trigeminal function should be assessed in greater detail compared
      to previous work. METHODS: A total of 95 healthy subjects participated in the
      study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising
      tests of odor identification, odor discrimination, and odor threshold. Trigeminal
      sensitivity was assessed on a psychophysical level using a lateralization
      paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were
      recorded; stimuli were presented in different concentrations to the left and
      right nostril. RESULTS: Olfactory thresholds exhibited an age-related increase
      while the outcome of psychophysical trigeminal tests was not significantly
      affected by age. In contrast, there was no significant main effect of the factor
      'sex' for olfactory tests, while women scored higher than men in the trigeminal
      task. ERP to olfactory and trigeminal stimuli exhibited a relationship to
      stimulus concentration, age, and sex with youngest women showing largest
      amplitudes and shortest latencies. There was no significant main effect of left-
      or right-sided stimulation on ERP. Measures of olfactory function were found to
      correlate with parameters of olfactory ERP even when controlling for the
      subject's age. In addition, correlations between scores in the lateralization
      task and parameters of the trigeminal ERP were found. CONCLUSIONS: Based on
      electrophysiological data obtained in a large sample size the present results
      established an age-related loss of olfactory and trigeminal function, which
      appears to be almost linear. Further, the present results emphasize that
      responses to chemosensory stimuli are related to sex, while the side of
      stimulation does not play a major role in the presently used paradigm. Finally,
      these data establish the lateralization paradigm as a psychophysical tool to
      investigate intranasal trigeminal function. SIGNIFICANCE: The present results
      obtained in a representative group of healthy subjects establishes a
      comprehensive set of data, which will serve as reference for future work in this
      area of research.

PMID- 16651025
TI  - Engineering of beta-propeller protein scaffolds by multiple gene duplication and
      fusion of an idealized WD repeat.
AB  - The ability to design specific amino acid sequences that fold into desired
      structures is central to engineering novel proteins. Protein design is also a
      good method to assess our understanding of sequence-structure and structure
      function relationships. While beta-sheet structures are important elements of
      protein architecture, it has traditionally been more difficult to design beta
      proteins than alpha-helical proteins. Taking advantage of the tandem repeated
      sequences that form the structural building blocks in a group of beta-propeller
      proteins; we have used a consensus design approach to engineer modular and
      relatively large scaffolds. An idealized WD repeat was designed from a structure
      based sequence alignment with a set of structural guidelines. Using a plasmid
      sequential ligation strategy, artificial concatemeric genes with up to 10 copies
      of this idealized repeat were then constructed. Corresponding proteins with 4
      through to 10 WD repeats were soluble when over-expressed in Escherichia coli.
      Notably, they were sufficiently stable in vivo surviving attack from endogenous
      proteases, and maintained a homogeneous, non-aggregated form in vitro. The
      results show that the beta-propeller scaffold is an attractive platform for
      future engineering work, particularly in experiments in which directed evolution
      techniques might improve the stability of the molecules and/or tailor them for a
      specific function.

PMID- 16651026
TI  - Lipid metabolism, atherogenesis and CD1-restricted antigen presentation.
AB  - CD1 molecules are a family of major histocompatibility complex (MHC)-related
      glycoproteins that present lipid and glycolipid antigens to T cells.
      Interestingly, it has been demonstrated that CD1d-restricted T cells have a
      pathogenic role in atherosclerosis. Recent studies suggest an association between
      the cellular machinery that loads CD1 molecules with glycolipids and several key
      proteins in lipid metabolism. These proteins include the sphingolipid activator
      proteins (SAPs), microsomal triglyceride transfer protein (MTP) and
      apolipoprotein E (apoE). MTP and SAPs seem to be crucial for loading CD1d with
      lipids in the endoplasmic reticulum and endosomal compartments, respectively,
      whereas apoE facilitates efficient uptake and delivery of exogenous lipid
      antigens to CD1d in endosomal compartments. These studies reveal new and
      unexpected relationships between lipid metabolism and antigen presentation by CD1
      molecules. Targeting this pathway of immune activation might have therapeutic
      potential for the treatment of chronic inflammatory diseases.

PMID- 16651027
TI  - Why substrate depletion has apparent first-order kinetics in enzymatic digestion.
AB  - A number of enzyme digestion assays show apparent first-order kinetics of
      reactant depletion. There are four possible explanations of this phenomenon: (i)
      the reaction is dominated by a first-order limiting step, (ii) the digestion
      follows a pseudo-first-order kinetics under the excess of a reactant species,
      (iii) the first-order kinetics is only applicable to the slow transient of the
      reaction, or (iv) the aggregate behavior of the reaction pathway produces
      behavior indistinguishable from the first-order kinetics. In this paper, we
      investigate the kinetics for protein digestion by formulating rate equations for
      two proposed mechanisms, namely the one-by-one mechanism and the zipper
      mechanism. Our analysis shows that the kinetics of protein digestion follows
      apparent first-order kinetics irrespective of the mechanism for low initial
      substrate concentration compared to the initial enzyme concentration. Also, our
      results provide an explanation for experimental observations and suggest a new
      experimental protocol that could reveal information on the mechanism of
      digestion.

PMID- 16651028
TI  - In vivo transduction by intravenous injection of a lentiviral vector expressing
      human ADA into neonatal ADA gene knockout mice: a novel form of enzyme
      replacement therapy for ADA deficiency.
AB  - Using a mouse model of adenosine deaminase-deficient severe combined immune
      deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method
      of gene transfer for the sustained systemic expression of human ADA as enzyme
      replacement therapy. The method of delivery is a human immunodeficiency virus 1
      based lentiviral vector given systemically by intravenous injection on day 1 to 2
      of life. In this article we characterize the biodistribution of the integrated
      vector, the expression levels of ADA enzyme activity in various tissues, as well
      as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype
      in this mouse model. The long-term expression of enzymatically active ADA
      achieved by this method, primarily from transduction of liver and lung, restored
      immunologic function and significantly extended survival. These studies
      illustrate the potential for sustained in vivo production of enzymatically active
      ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.

PMID- 16651029
TI  - N-terminal proBNP levels in patients with Chagas disease: a marker of systolic
      and diastolic dysfunction of the left ventricle.
AB  - AIMS: NT-proBNP levels are known to be elevated in systolic and diastolic
      dysfunction. Doppler indices of diastolic dysfunction (DD) have been shown to
      have prognostic value in patients with Chagas' cardiomyopathy (CC). However, the
      additional value of NT-proBNP levels in further stratifying these patients
      according to DD has not been established. This study analyzed the correlation of
      N-terminal proBNP (NT-proBNP) levels with systolic and diastolic function in
      patients with CC. METHODS AND RESULTS: NT-proBNP levels were measured in 59
      patients with dilated cardiomyopathy due to Chagas disease without other systemic
      illness that were studied by Doppler echocardiography, including left atrial
      volume (LAV) calculation and tissue Doppler evaluation of LV longitudinal
      function. Univariate analysis showed a strong correlation of NT-proBNP values
      with LVEF (r=-0.733, p<0.001) and a weak correlation with most Doppler
      echocardiographic parameters of diastolic function. On a multivariate analysis,
      LVEF and LAV volume emerged as correlating with elevated levels of the NT-proBNP.
      Patients with restrictive filling pattern (n=10), when compared to other patterns
      of DD, (n=49), showed a lower LVEF (25.4+/-6.4% vs. 39.8+/-9.4, p<0.001), a
      larger LAV (50.1+/-17.2 vs. 37.7+/-15.6 ml/m(2), p=0.004) and higher NT-proBNP
      levels (median+/-IQR: 3488+/-3056 vs. 492+/-700 pg/dl, p<0.001). A marked
      elevated concentration of NT-proBNP (> or =800 pg/ml) had a sensitivity of 90.0%,
      specificity of 70.5%, positive predictive value of 40.9% and negative predictive
      value of 96.9% for detecting a restrictive filling pattern. CONCLUSION: In
      patients with CC, NT-proBNP augmentation is a marker of LV dysfunction, with
      higher levels correlating with the more severe forms of both systolic and
      diastolic dysfunction.

PMID- 16651031
TI  - Relationship between prostaglandin E2 and vascular endothelial growth factor
      (VEGF) in angiogenesis in human vascular endothelial cells.
AB  - To address the role of prostaglandin E2 (PGE2) in tube formation of endothelial
      cells and the relationships between the action of PGE2 and vascular endothelial
      growth factor (VEGF), cultured human umbilical vein endothelial cells (HUVECs)
      were used to evaluate tube formation on Matrigel and the expression of
      angiogenesis-related genes. PGE2 treatment stimulated the tube-like formation of
      HUVECs. Whereas VEGF-induced tube formation was significantly suppressed by ETYA,
      an inhibitor of arachidonic acid metabolism, or SU5614, an inhibitor of VEGF
      receptor tyrosine kinase, the stimulatory effect of PGE2 was observed in the
      presence of ETYA or SU5614. Thus, PGE2 counteracted both ETYA- and SU5614-induced
      blockage of angiogenesis in the presence of VEGF. VEGF induced cyclooxygenase
      (COX) -2 mRNA expression in HUVECs and increased the PGE2 concentration in the
      medium. PGE2 treatment enhanced the expression of VEGF mRNA. These findings
      suggest that PGE2 directly stimulates angiogenesis, apart from VEGF signaling,
      and further induces VEGF expression in HUVECs. In addition, the effect of VEGF on
      angiogenesis may be mediated, in part, by PGE2 secretion.

PMID- 16651032
TI  - Effect of gap junction uncoupler heptanol on resistance arteries reactivity in
      experimental models of diabetes, hyperlipemia and hyperlipemia-diabetes.
AB  - The understanding of the involvement of the gap junctions (GJ) in the vascular
      reactivity is an ongoing effort. In this study we questioned on impact of
      pathologies such as diabetes, hyperlipemia, and simultaneous hyperlipemia
      diabetes on GJ involvement in the contractile/relaxant response of the mesenteric
      resistance arteries. To this purpose, four groups of Golden Syrian hamsters were
      used: (i) diabetics (D), injected by streptozotocin, (ii) hyperlipemics (H), fed
      the standard chow of the species supplemented with 3% cholesterol and 15% butter,
      (iii) simultaneously hyperlipemic-diabetics (HD), and (iv) controls (C), age
      matched normal healthy animals. At 24 weeks after the beginning of the
      experiment, the vascular reactivity of the resistance arteries was measured by
      the myograph technique in the presence/absence of 1 mM Heptanol (Hep) and of
      vasoconstrictors and vasodilators. The results showed that: (i) in pathological
      conditions 1 mM Hep significantly impaired the constrictor response of the
      hamster resistance arteries to both 10(-5) M NA (noradrenaline, agonist of
      alpha(1)-adrenoceptors) and 64.1 mM K+ (potassium ion, the major intracellular
      cation). The impairment occur in the group range: HD < H < D < C being the
      highest at the simultaneous insult of hyperlipemia and diabetes; (ii)
      independently of the pathological condition, 1 mM Hep abolishes both endothelium
      dependent and independent relaxation of the hamster resistance arteries. At 1 mM
      Hep we noticed a reversible effect on endothelium-dependent relaxation that may
      be partially restored (in normal) in the presence of L-arginine. It is hoped that
      these results may contribute to understanding of the involvement of GJ in
      vascular pathology/dysfunction.

PMID- 16651034
TI  - Diltiazem, an antagonist of calcium channels, reduces norepinephrine in the rat
      myocardium.
AB  - The present study examined the effect of diltiazem, a calcium channel antagonist,
      on potassium (K(+)) depolarization-induced norepinephrine (NE) release in rat
      myocardium using a flexibly mounted microdialysis technique. When high
      concentration of KCl (70 mM) was directly infused in rat heart through a
      microdialysis probe, the level of NE gradually increased in a time dependent
      manner. However, when a high concentration of KCl (70 mM) was administered to
      diltiazem-pretreated animals, it failed to increase the KCl-induced dialysate NE.
      These results suggest that calcium (Ca(2+)) may play a key role in K(+)
      depolarization-induced NE release in the myocardium.

PMID- 16651035
TI  - Determination of three bile acids in artificial Calculus Bovis and its medicinal
      preparations by micellar electrokinetic capillary electrophoresis.
AB  - A micellar electrokinetic capillary electrophoresis (MEKCE) method for the
      determination of cholic acid (CA), hyodeoxycholic acid (HDCA) and
      chenodeoxycholic acid (CDCA) in artificial Calculus Bovis and its four medicinal
      preparations is described. The buffer solution consisted of 40 mM disodic
      phosphate and 40 mM sodium dodecylsulfate (SDS) adjusted to pH 9.0. UV detection
      was set to 200 nm. Under optimum conditions, the analytes were baseline separated
      within 11min. The linear calibration range was 12.1-970 microgml(-1) for CA and
      18.8-950 microgml(-1) for HDCA and CDCA, respectively. It was found that overall
      recoveries were within the range of 98-102%, and R.S.D.s were less than 5% for
      the analytes. This method, due to its convenience, high accuracy and good
      reproducibility can be employed in quality control of artificial Calculus Bovis
      and its medicinal preparations.

PMID- 16651033
TI  - Expression of fractalkine and fractalkine receptor in urinary bladder after
      cyclophosphamide (CYP)-induced cystitis.
AB  - Alterations in the expression of the chemokine, fractalkine (CX3CL1), were
      examined in the urinary bladder after cyclophosphamide (CYP)-induced cystitis of
      varying duration: acute (4 h or 48 h), or chronic (10 day). CYP-induced cystitis
      significantly (p<or=0.01) increased fractalkine protein expression in the urinary
      bladder with acute (48 h) and chronic CYP treatment. Western blot analysis also
      demonstrated significantly (p<or=0.01) increased fractalkine expression in the
      whole urinary bladder with acute (1.5-2.2-fold) and chronic (3-fold) CYP-induced
      cystitis. Immunohistochemistry for fractalkine-immunoreactivity revealed little
      fractalkine-IR in control or acute (4 h) CYP-treated rat urinary bladders except
      in a vascular bed but showed no colocalization with nerve fibers in the
      suburothelial plexus in any experimental group. However, expression was
      significantly (p<or=0.001) upregulated in the urothelium with 48 h or chronic CYP
      treatment. Similarly, fractalkine receptor (CX3CR1)-IR was significantly
      (p<or=0.001) upregulated in the urothelium with 48 h or chronic CYP treatment.
      These studies demonstrated upregulation of the chemokine, fractalkine, in the
      urinary bladder and specifically in the urothelium with CYP-induced cystitis.
      Chemokines, and specifically, fractalkine, may be another class of
      neuromodulatory agents upregulated in the urinary bladder that can affect
      micturition function and sensory processing with cystitis and may represent
      novel, drug targets for cystitis.

PMID- 16651036
TI  - Transfusion-transmitted malaria: how satisfactory are current preventative
      measures?

PMID- 16651037
TI  - Gabapentin in the treatment of intractable idiopathic chronic cough: case
      reports.

PMID- 16651038
TI  - High-density lipoprotein cholesterol and sex difference in coronary heart disease
      risk.

PMID- 16651039
TI  - Associated atherothrombotic disease risk factors in diabetes and prediabetes.

PMID- 16651040
TI  - Response to differences in antibiotic prescribing.

PMID- 16651042
TI  - Cardiovascular abnormalities in hyperthyroidism.

PMID- 16651043
TI  - Dangerous kisses: Epstein-barr virus myocarditis mimicking myocardial infarction.

PMID- 16651044
TI  - Bilateral exophthalmos revealing a case of husband and wife sarcoidosis.

PMID- 16651045
TI  - Topical imiquimod for recurrent acyclovir-resistant HSV infection.

PMID- 16651046
TI  - A near-failing grade: federal planning for US healthcare.

PMID- 16651047
TI  - Does testosterone have a role in erectile function?
AB  - PURPOSE: Despite the well-established role of testosterone in enhancing libido,
      its exact contribution to erections in men remains unclear. The main objectives
      of this review are to clarify the role of testosterone in erectile function and
      evaluate its therapeutic value in men with erectile dysfunction (ED). METHODS:
      Review of the relevant literature (English, French, and Spanish) from 1939 to
      June 2005 was conducted using data sources from MEDLINE, endocrinology text
      books, and hand searching of cross-references from original articles and reviews.
      Clinical trials, animal studies, case reports, reviews, and guidelines of major
      associations were included. RESULTS: Animal and preliminary human studies suggest
      that testosterone may facilitate erection by acting as vasodilator of the penile
      arterioles and cavernous sinusoids. Following castration, most, but not all, men
      had partial or complete loss of erection. Hypogonadism is not a common finding in
      ED, occurring in about 5% of cases, and in general, there is lack of association
      between serum testosterone levels, when present in normal or moderately low
      levels, and erectile function. Most trials using testosterone for treatment of ED
      in hypogonadal men suffer from methodological problems and report inconsistent
      results, but overall, suggest that testosterone may be superior to placebo.
      Erectile function is more likely to improve with testosterone therapy in patients
      with severe degrees of hypogonadism. Testosterone treatment may ameliorate the
      response to the phosphodiesterase 5 (PDE5) inhibitors in hypogonadal men and men
      with low-normal serum testosterone. Repeated measurement of morning serum total
      testosterone is a fairly accurate and easy method to evaluate androgenecity, but
      measurement of free or bioavailable testosterone is recommended in conditions
      that alter the levels of sex-hormone-binding globulin (SHBG), such as in the
      elderly and in obesity. CONCLUSIONS: Available data suggest that in most men
      circulating levels of testosterone, well below the normal range, are essential
      for normal erection and that higher levels of serum testosterone may not have
      major impact on erectile function. Screening for hypogonadism in all men with ED
      is necessary to identify cases of severe hypogonadism and some cases of mild to
      moderate hypogonadism, who may benefit from testosterone treatment.

PMID- 16651048
TI  - Posttraumatic stress disorder: clinical features, pathophysiology, and treatment.
AB  - Posttraumatic stress disorder (PSTD), classified as an anxiety disorder, has
      become increasingly important because of wars overseas, natural disasters, and
      domestic violence. After trauma exposes the victim to actual or threatened death
      or serious injury, 3 dimensions of PTSD unfold: (1) reexperiencing the event with
      distressing recollections, dreams, flashbacks, and/or psychologic and physical
      distress; (2) persistent avoidance of stimuli that might invite memories or
      experiences of the trauma; and (3) increased arousal. Traumatic events sufficient
      to produce PTSD in susceptible subjects may reach a lifetime prevalence of 50% to
      90%. The actual lifetime prevalence of PTSD among US citizens is approximately
      8%, with the clinical course driven by pathophysiologic changes in the amygdala
      and hippocampus. Comorbid depression and other anxiety disorders are common.
      General principles of treatment include the immediate management of PTSD symptoms
      and signs; management of any trauma-related comorbid conditions; nonpharmacologic
      interventions including cognitive behavioral treatment; and psychopharmacologic
      agents including antidepressants (selective serotonin reuptake inhibitors most
      commonly), antianxiety medications, mood stabilizing drugs, and antipsychotics.
      This review of PTSD will provide the reader with a clearer understanding of this
      condition, an increased capacity to recognize and treat this syndrome, and a
      greater appreciation for the role of the internist in PTSD.

PMID- 16651049
TI  - Revisiting hereditary hemochromatosis: current concepts and progress.
AB  - Originally regarded as a rare affliction notable for its distinctive evolution to
      "bronze diabetes," hereditary hemochromatosis is now recognized as the most
      common genetic disorder in populations of European ancestry. Recent advances in
      our understanding of iron metabolism, the identification of the gene responsible
      for hemochromatosis, and large epidemiologic studies have changed the diagnostic
      approach toward patients with hereditary hemochromatosis and other forms of iron
      overload. This article reviews the pathophysiology, epidemiology, clinical
      features, diagnostic testing, and management of hemochromatosis for the primary
      care provider.

PMID- 16651050
TI  - Clinical perspectives of statin-induced rhabdomyolysis.
AB  - Fear of muscle toxicity remains a major reason that patients with hyperlipidemia
      are undertreated. Recent evaluations of statin-induced rhabdomyolysis offer new
      insights on the clinical management of both muscle symptoms and hyperlipidemia
      after rhabdomyolysis. The incidence of statin-induced rhabdomyolysis is higher in
      practice than in controlled trials in which high-risk subjects are excluded.
      Accepted risks include age; renal, hepatic, and thyroid dysfunction; and
      hypertriglyceridemia. New findings suggest that exercise, Asian race, and
      perioperative status also may increase the risk of statin muscle toxicity. The
      proposed causes and the relationship of drug levels to statin rhabdomyolysis are
      briefly reviewed along with the problems with the pharmacokinetic theory. Data
      suggesting that patients with certain metabolic abnormalities are predisposed to
      statin rhabdomyolysis are presented. The evaluation and treatment of patients'
      muscle symptoms and hyperlipidemia after statin rhabdomyolysis are presented.
      Patients whose symptoms are related to other disorders need to be identified.
      Lipid management of those whose symptoms are statin-related is reviewed including
      treatment suggestions.

PMID- 16651051
TI  - Broadening the differential diagnosis.

PMID- 16651052
TI  - A prickly problem.

PMID- 16651053
TI  - Witness to a heart attack?

PMID- 16651054
TI  - Health outcomes in older men with localized prostate cancer: results from the
      Prostate Cancer Outcomes Study.
AB  - PURPOSE: We compared health-related quality-of-life (HRQOL) outcomes and survival
      of men with localized prostate cancer who received aggressive treatment with
      those receiving conservative management. METHODS: We conducted a population-based
      cohort study of men aged 75 to 84 years when diagnosed with a clinically
      localized cancer in 1994 or 1995. We used medical record abstractions and patient
      surveys to obtain clinical and HRQOL data at diagnosis and 24-month follow-up. We
      used a propensity score method to adjust for baseline differences between men
      treated with radical prostatectomy or radiation therapy (n = 175) and men who
      received hormone therapy or no treatment (n = 290). Propensity scores were used
      in regression analyses comparing HRQOL outcomes between treatment groups. Overall
      and disease-specific survivals were estimated with multivariate proportional
      hazards models. RESULTS: At 24 months following diagnosis, aggressively treated
      men were more likely to report daily urinary leakage (odds ratio [OR] = 2.9, 95%
      confidence interval [CI] 1.2-7.0) and to be bothered by urinary problems (OR =
      5.1, 95% CI, 1.3-9.1) and sexual problems (OR = 2.8, 95% CI, 1.2-6.3). The
      adjusted disease-specific mortality hazard ratio was 0.43 (95% CI, 0.15, 1.28),
      favoring aggressive treatment. However, the absolute 5-year disease-specific
      survival difference was only 6% (98% vs 92%). Over 80% of all deaths were from
      other causes. CONCLUSIONS: Aggressive treatment was associated with significant
      decreases in disease-specific HRQOL. However, men who were aggressively treated
      for localized cancer had a minimally reduced absolute risk of dying from prostate
      cancer. Physicians and older patients should consider these outcomes in making
      decisions about screening and treatment.

PMID- 16651055
TI  - Estradiol, testosterone, and the risk for hip fractures in elderly men from the
      Framingham Study.
AB  - BACKGROUND: Low serum estradiol has been more strongly associated with low bone
      mineral density in elderly men than has testosterone, but its association with
      incident hip fracture is unknown. We examined whether low estradiol increases the
      risk for future hip fracture among men and explored whether testosterone levels
      influence this risk. METHODS: We examined 793 men (mean age = 71 years) evaluated
      between 1981 and 1983, who had estradiol measures and no history of hip fracture,
      and followed until the end of 1999. Total estradiol and testosterone were
      measured between 1981 and 1983. Hip fractures were identified and confirmed
      through medical records review through the end of 1999. We created 3 groups of
      men based on estradiol levels and performed a Cox-proportional hazards model to
      examine the risk for incident hip fracture, adjusted for age, body mass index,
      height, and smoking status. We performed similar analyses based on testosterone
      levels, and then based on both estradiol and testosterone levels together.
      RESULTS: There were 39 men who sustained an atraumatic hip fracture over follow
      up. Incidence rates for hip fracture (per 1000 person-years) were 11.0, 3.4, and
      3.9 for the low (2.0-18.1 pg/mL [7-67 pmol/L]), middle (18.2-34.2 pg/mL [67-125
      pmol/L]), and high (> or =34.3 pg/mL [> or =126 pmol/L]) estradiol groups,
      respectively. With adjustment for age, body mass index, height, and smoking
      status, the adjusted hazard ratios for men in the low and middle estradiol
      groups, relative to the high group, were 3.1 (95% confidence interval [CI], 1.4
      6.9) and 0.9 (95% CI, 0.4-2.0), respectively. In similar adjusted analyses
      evaluating men by their testosterone levels, we found no significant increased
      risk for hip fracture. However, in analyses in which we grouped men by both
      estradiol and testosterone levels, we found that men with both low estradiol and
      low testosterone levels had the greatest risk for hip fracture (adjusted hazard
      ratio: 6.5, 95% CI, 2.9-14.3). CONCLUSION: Men with low estradiol levels are at
      an increased risk for future hip fracture. Men with both low estradiol and low
      testosterone levels seem to be at greatest risk for hip fracture.

PMID- 16651056
TI  - Moderate alcohol consumption and safety of lovastatin and warfarin among men: the
      post-coronary artery bypass graft trial.
AB  - PURPOSE: Although moderate drinking has been associated with lower mortality
      among patients with coronary heart disease, its safety among patients taking
      common cardiac medications is unknown. SUBJECTS AND METHODS: We studied 1244 men
      enrolled in the Post-Coronary Artery Bypass Graft (CABG) Trial who had undergone
      previous coronary bypass surgery. Participants were randomly assigned to
      lovastatin in low (mean 4 mg) or high (mean 76 mg) doses and to low-dose warfarin
      (mean international normalized ratio [INR] 1.4, goal INR <2.0) or placebo in a
      factorial design. Participants underwent routine measurement of alanine
      aminotransferase (ALT) and INR levels every 6 to 12 weeks for 4 to 5 years. We
      categorized weekly alcohol intake as abstention (<1 drink), light (1-6 drinks),
      moderate (7-13 drinks), and heavier (> or =14 drinks). RESULTS: During follow-up,
      66% of men taking warfarin had an INR of 2.0 or higher, and 7% of men had an ALT
      of 80 IU/L or higher. Maximum INR (P = .72) and ALT (P = .51) levels did not
      differ across categories of alcohol intake. The risks of an INR of 2.0 or higher
      were 67%, 66%, 68%, and 61% among non-, light, moderate, and heavier drinkers (P
      = .86), respectively. The corresponding risks of an ALT of 80 IU/L or more were
      8%, 10%, 9%, and 6% (P = .70), respectively. CONCLUSION: Moderate drinking did
      not adversely influence the safety of low-dose warfarin or even high-dose
      lovastatin among men in this randomized trial, as measured by INR and ALT levels.

PMID- 16651057
TI  - Characteristics associated with sustained abstinence from smoking among patients
      with COPD.
AB  - PURPOSE: Smoking cessation is the mainstay of recommended treatment for chronic
      obstructive pulmonary disease (COPD), yet many continue smoking. This study seeks
      to understand the characteristics of patients with COPD who have quit and those
      who have not quit to identify important factors to evaluate in smoking-cessation
      interventions. SUBJECTS/METHODS: A cross-sectional survey of a random sample of
      1.5 million, predominantly male Veterans Administration enrollees. Of the
      respondents (63% [n = 887,775]), those with at least 1 COPD visit, a smoking
      history, and aged more than 34 years were included in this analysis (n = 89 337).
      Differences in demographics, functional status, comorbidities, and provider
      patient interactions were evaluated for current and former smokers. RESULTS:
      Ninety-seven percent of the cohort with COPD was male. Former smokers (n = 58
      482) were older (mean age of 69.6 vs 62.8, P<.001) and had more cardiac
      comorbidities, but better mental health (Mean Mental Component Summary score from
      the Veterans Short Form-36 +/- standard deviation of 43.4 +/- 13.2 vs 39.9 +/-
      13.7, P<.001) than current smokers (n = 25 595), respectively. In addition,
      former smokers more actively participated in their health care and had a better
      relationship with their provider than current smokers. CONCLUSION: Former smokers
      with COPD were older, had more cardiac comorbidities, better mental health, and
      better perceived provider-patient interactions than active smokers. This study
      highlights the importance of screening participants with COPD who are enrolling
      in forthcoming smoking cessation trials for mental illnesses. In addition,
      developing interventions that address psychiatric comorbidities and potentially
      improve provider-patient communication may be other key areas to evaluate in
      future smoking cessation trials in patients with COPD.

PMID- 16651058
TI  - Quality of life in patients with atrial fibrillation: a systematic review.
AB  - The impact of atrial fibrillation (AF) on patients' quality of life (QoL) has yet
      to be fully elucidated in a systematic manner. This article examines QoL in
      "general" patients with AF as well as the effects that rate and/or rhythm-control
      interventions have on QoL. Patients with AF have significantly poorer QoL
      compared with healthy controls, the general population, and other patients with
      coronary heart disease. Studies examining rate or rhythm-control strategies alone
      demonstrate improved QoL after intervention. Three of the four large randomized
      control trials (STAF, PIAF, RACE) comparing rate versus rhythm control
      demonstrated a greater improvement in QoL in patients receiving rate control.
      However, the AFFIRM trial revealed a similar improvement in QoL for both rate and
      rhythm-control groups. The data, although frequently compromised by various
      methodologic weaknesses, suggest that patients with AF have impaired QoL, and
      that QoL can be significantly improved through rate or rhythm-control strategies.

PMID- 16651059
TI  - Ocular syphilis in HIV-positive patients receiving highly active antiretroviral
      therapy.
AB  - BACKGROUND: From October 2001 to October 2002, we have observed a surprisingly
      high incidence of ocular syphilis in human immunodeficiency virus-positive (HIV+)
      patients receiving highly active antiretroviral therapy at our clinic. METHODS:
      We conducted a retrospective chart and patient database review. RESULTS: From
      1997 to 2002, 455 patients in our clinic were screened for syphilis; 320 were
      screened from 2001 to 2002; 7.3% of patients (33/455) were diagnosed with
      syphilis. During the past year, syphilis was diagnosed in 7.5% of patients
      (24/320), of whom 13% (3/24) had ocular syphilis. We estimate the prevalence of
      ocular syphilis in HIV+ patients on highly active antiretroviral therapy screened
      for syphilis to be 9% (3/33). Presenting symptoms included blurred vision, loss
      of vision, central scotomas, and bilateral ocular involvement. The most common
      ocular manifestation of syphilis was posterior chamber uveitis; one patient also
      had a retinal detachment. All patients demonstrated reactive rapid plasma reagin
      and fluorescent treponemal antibody absorption test results, cerebrospinal fluid
      pleocytosis, and elevated total protein. Each patient received a 21-day course of
      intravenous penicillin G (24 million units daily) with improvement of visual
      symptoms. CONCLUSION: Our data demonstrate an unexpectedly high incidence of
      ocular syphilis in our HIV+ patients receiving highly active antiretroviral
      therapy during the past year. A diagnosis of ocular syphilis should be considered
      in any HIV+ patient who presents with visual symptoms, irrespective of the
      patient's CD4 count.

PMID- 16651060
TI  - Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: a meta-analysis.
AB  - PURPOSE: Because dyspeptic symptoms are far more prevalent than ulcer
      complications in users of nonsteroidal anti-inflammatory drugs (NSAIDs), economic
      models indicate that dyspepsia rates (not ulcer complications) are the major
      determinant of cost-effectiveness in treating arthritis. We performed a meta
      analysis to compare rates of dyspepsia for two common therapies in high-risk
      patients with arthritis: cyclooxygenase-2 inhibitor (Coxib) alone and combination
      therapy with a nonselective NSAID and a proton pump inhibitor (PPI) (NSAID+PPI).
      METHODS: We performed a systematic review to identify trials comparing either a
      Coxib versus NSAID or NSAID+PPI versus NSAID in chronic arthritis. We selected
      studies that report incident dyspepsia, defined a priori as "epigastric pain,"
      "dyspepsia," and "nausea." We then performed meta-analysis to compare the
      relative risk reduction and absolute risk reduction of dyspepsia for Coxib versus
      NSAID and NSAID+PPI versus NSAID. RESULTS: Meta-analysis of 26 studies comparing
      dyspepsia between Coxibs and NSAIDs revealed a 12% relative risk reduction for
      Coxibs with an absolute risk reduction of 3.7%. Meta-analysis of four studies
      comparing dyspepsia between the NSAID+PPI combination and NSAIDs alone revealed a
      66% relative risk reduction for NSAID+PPI with an absolute risk reduction of 9%.
      Compared with the NSAID strategy, the number needed to treat to prevent dyspepsia
      was 27 for Coxibs and 11 for NSAID+PPI. CONCLUSION: NSAID+PPI affords greater
      risk reduction for dyspepsia than Coxibs when compared with the common baseline
      of NSAIDs. Because there are limited head-to-head data comparing Coxibs versus
      NSAID+PPI, these data provide the best indirect evidence that NSAID+PPI may be
      superior to Coxibs in minimizing incident dyspepsia.

PMID- 16651061
TI  - Opting in: part-time careers in academic medicine.

PMID- 16651063
TI  - Prophylaxis and treatment of implant-related infections by antibiotic-coated
      implants: a review.
AB  - Implant-related infection is a feared complication in orthopedic and trauma
      surgery with tremendous consequences for the patient. To reduce this risk,
      administration of perioperative antibiotic prophylaxis is a routine procedure in
      orthopedic surgery. A local delivery system for antibiotics based on a polymer
      implant coating has been developed to optimize the prophylaxis. In an animal
      experiment, the efficacy of local prophylaxis of gentamicin was compared to a
      systemic single shot of gentamicin and to a combination of both administrations.
      The medullary cavities of rat tibiae were contaminated with Staphylococcus aureus
      and titanium K-wires were implanted into the medullary canals. For local
      antibiotic therapy, the implants were coated with poly(D,L-Lactide) (PDLLA)
      loaded with gentamicin. All the animals not treated with local and systemic
      application of the antibiotic developed osteomyelitis and all cultures of the
      implants tested positive for S. aureus. Onset of infection was prevented in 80
      90% of animals treated with gentamicin-coated K-wires, with and without systemic
      prophylaxis. Gentamicin-coated intramedullary tibial nails are CE-certified for
      Europe and Canada and several patients have already been treated for implant
      related infection. Up to now, eight patients with open tibia fractures have been
      treated with an unreamed tibial nail (UTN) coated with PDLLA and gentamicin. In
      the 1-year follow up, none of the patients developed an infection. A prospective
      randomized clinical documentation is currently in progress. So far, the results
      suggest that a local application of gentamicin from PDLLA-coated implants might
      support systemic antibiotic prophylaxis in preventing implant-associated
      osteomyelitis.

PMID- 16651066
TI  - Tolerance of staphylococci to bactericidal antibiotics.
AB  - Antibiotic therapy for deep-seated staphylococcal infections, especially when
      they are associated with artificial devices used for orthopedic surgery is often
      associated with failure. Standard anti-staphylococcal bactericidal antibiotics,
      such as semi-synthetic penicillins, cephalosporins, or glycopeptides, are
      effective when given prophylactically in clinical conditions or experimental
      trials of implant-related infections. However, the efficacy of all anti
      staphylococcal agents is seriously diminished on already established implant
      related deep-seated infections, which then frequently require surgical implant
      removal to obtain a cure. The failure of antibiotic therapy to cure established
      staphylococcal foreign-body infections may arise in part from a broad-spectrum
      phenotypic tolerance expressed in vivo to different classes of antimicrobial
      agents. The molecular and physiological mechanisms of this in vivo tolerance
      remain poorly understood.

PMID- 16651067
TI  - State of the knowledge of bacterial resistance.
AB  - Bacteria have adapted a variety of different ways to acquire antibiotic
      resistance, fostering the rapid development of resistance within a short
      evolutionary time. The general genetic basis of events leading to and promoting
      antibiotic resistance formation in bacteria are presented and exemplified by
      showing the evolution of methicillin, glycopeptide, linezolid, and ketolide
      resistance in Staphylococcus aureus.

PMID- 16651068
TI  - The small colony variant (SCV) concept -- the role of staphylococcal SCVs in
      persistent infections.
AB  - The recovery of small colony variants (SCVs) from clinical specimens was first
      described at the beginning of the last century. However, not until the past
      decade was an association of these variants with chronic, recurrent, and
      persistent infections such as chronic osteomyelitis and persistent skin and
      softtissue infection described. Since then, a number of reports and prospective
      studies have supported a pathogenic role for SCVs in disease. Biochemical and
      other characteristics of SCVs have suggested a link between electron-transport
      defective SCV strains and persistent infections, however, the strains examined
      were genetically undefined SCVs. Therefore, a stable mutant in electron transport
      was generated by interrupting one of the hemin biosynthetic genes, hemB, in
      Staphylococcus aureus. This mutant showed characteristics typical of clinical
      SCVs such as slow growth, decreased pigment formation, low coagulase activity,
      reduced hemolytic activity, and resistance to aminoglycosides. Furthermore, the
      mutant was able to persist within cultured endothelial cells due to decreased a
      toxin production. It was suggested that the intracellular location of this
      subpopulation might shield the variants from host defenses and antibiotics, thus
      providing one explanation for the difficulty in removing SCVs from host tissues.
      Therefore, a defect in the electron-transport system allows S. aureus SCVs to
      resist aminoglycosides and persist intracellularly. Because of their fastidious
      growth characteristics, they are easily missed or misidentified in the clinical
      laboratory. Therefore, when an infection persists for weeks or months or fails to
      respond to antimicrobial therapy, clinicians as well as laboratory personnel
      should consider further efforts to search for this staphylococcal subpopulation.

PMID- 16651069
TI  - Staphylococci and implant surfaces: a review.
AB  - Surfaces of internal fracture fixation implants are generally designed to
      encourage soft- and/or hard-tissue adherence, eventually leading to tissue or
      osseo integration. Unfortunately, this feature may also encourage bacterial
      adhesion. About half of the two million cases of nosocomial infections per year
      in the US are associated with indwelling devices. In the UK, implant-associated
      infections are estimated to cost pound 7-11 million per year, and with the rise
      in antibiotic-resistant bacteria, are an important issue. Soft-tissue infections
      and osteomyelitis are serious complications associated with implants,
      particularly open fractures, external fixation devices, and intramedullary
      nailing. Consequences of implant-associated infections include prolonged
      hospitalization with systemic antibiotic therapy, several revision procedures,
      possible amputation, and even death. This review discusses the issue of implant
      associated infections and some of the methods used to prevent bacterial adhesion
      to osteosynthesis implants.

PMID- 16651070
TI  - Antimicrobial peptides: review of their application in musculoskeletal
      infections.
AB  - Antimicrobial resistance is expected to increase the burden of osteomyelitis
      drastically. The rise in resistant bacterial strains is driving researchers to
      find new treatment options. As a potential new antibiotic class, antimicrobial
      peptides (AMPs) combine several attractive intrinsic properties. Their minimal
      propensity for inducing antimicrobial resistance could be of particular clinical
      significance. AMPs act as an essential part of the innate immune system and have
      been identified in virtually all forms of life. These short, positively charged
      peptides have a combined pore-forming and intracellular killing effect on a broad
      range of microorganisms. Their reported spectrum of action includes resistant
      bacterial strains, viruses, and fungi. Moreover, immunomodulating, antitumoric,
      and angiogenic mechanisms have been reported. We have designed degradable and
      nondegradable drug-release systems for local treatment with AMPs. In animal
      models of osteomyelitis, these systems reduced bone infection caused by both
      resistant and nonresistant strains. The systemic application of several peptides
      for experimental detection and treatment of bone and soft-tissue infection is
      also discussed in this review. Radioactive-labeled peptides have accurately
      discriminated sterile inflammation from active infection in imaging studies.
      Successful preclinical studies of AMPs indicate that clinical evaluation of these
      powerful antibiotic agents is in order.

PMID- 16651071
TI  - Staphylococcus aureus capsular material promotes osteoclast formation.
AB  - Osteomyelitis, which is most frequently due to infection by Staphylococcus
      aureus, commonly causes bone destruction. S. aureus is known to secrete a number
      of surface-associated proteins that are potent stimulators of bone resorption.
      The precise cellular and humoral mechanisms that mediate this stimulatory effect
      are uncertain. In this study, we have determined whether osteoclast formation and
      resorption is directly promoted by surface-associated proteins. Surface
      associated material (SAM) obtained from a 24-hour culture of S. aureus was added
      to cultures of mouse and human monocytes. Human monocyte cultures were incubated
      in the presence and absence of a soluble receptor activator of nuclear factor
      kappa B ligand (RANKL) and macrophage colony stimulating factor (M-CSF). In
      cultures where M-CSF, RANKL, and SAM were added together, osteoclast formation
      did not exceed that seen in cultures with M-CSF and RANKL. In keeping with this
      finding, SAM did not increase osteoclast formation and resorption when mouse
      monocytes were cocultured with RANKL-expressing osteoblasts. In the absence of
      RANKL, however, SAM was capable of inducing osteoclast formation in cultures of
      human monocytes. This finding was evidenced by the generation of vitronectin
      receptor and tartrate-resistant acid phosphatasepositive multinucleated cells
      that were capable of lacunar resorption. Inhibitors of RANKL-dependent (RANK:Fc,
      OPG) and RANKL-independent (anti-TNF-alpha, gp130, IL-8, TGF-beta) osteoclast
      formation did not inhibit SAM-induced osteoclast formation. SAM did not stimulate
      mature osteoclast resorption activity. These findings indicate that RANKL, which
      is present in the circulation as a soluble factor, does not play a role in
      osteoclast formation in the presence of S. aureus SAM and that S. aureus SAM
      contains a soluble factor that promotes osteoclast formation by a RANKL
      independent mechanism.

PMID- 16651072
TI  - Histology of osteosynthesis associated bone infection.
AB  - The introduction to this paper summarizes the small amount of information
      currently published on the histological changes that accompany posttraumatic
      osteomyelitis in man in addition to other information to aid understanding of
      this topic. The development of three cases of posttraumatic osteomyelitis and the
      histological analysis of important tissue areas harvested during debridement are
      described in detail. Two of the patients suffered from diaphyseal fractures, one
      of which was nailed and the other plated. The third patient had an epi
      metaphyseal fracture, which was later plated with the additional use of an
      autogenous bone graft. The histological examination consisted of embedding the
      undecalcified tissue specimens in methylmethacrylate and cutting with a diamond
      saw or a special microtome. Bone necrosis, damaged soft tissue around it, and
      penetration of bacteria are the prominent etiological features for the onset of
      osteomyelitis. The distribution of bone necrosis depends mainly on trauma, the
      care of the surgeon, and the type of osteosynthesis. Loose dead bone and bone
      pieces demarcated by osteoclastic activity are transformed into sequestra
      surrounded by tissue that exhibits different infection activities according to
      the state of spontaneous development or treatment. Remodeling of bone necrosis
      from the living bone is slow and depends on many factors. New bone formation is
      mainly subperiosteal, embedding osteomyelitic areas if the periosteum is not
      destroyed.

PMID- 16651073
TI  - Diagnosis and treatment of infections associated with fracture-fixation devices.
AB  - The pathogenesis of infections associated with fracture-fixation devices is
      related to microorganisms growing in biofilms, which render these infections
      difficult to treat. These infections are classified as early (<2 weeks), delayed
      (2-10 weeks) or late infections (>10 weeks) according to the implant surgery.
      Most infections are caused by staphylococci and are acquired during trauma (in
      penetrating injuries) or subsequent fracture-fixation procedures. A combination
      of clinical, laboratory, histopathology, microbiology, and imaging studies are
      usually needed to accurately diagnose infection. Magnetic resonance imaging (MRI)
      and computed tomography (CT) scans are often used to diagnose infection and plan
      surgical treatment. Positron emission tomography (PET) and PET-CT are promising
      new tools for diagnosing implant-associated osteomyelitis. The treatment goal is
      achieving bone consolidation and avoiding development of chronic osteomyelitis.
      Successful treatment requires adequate surgical procedures combined with 6-12
      weeks of antimicrobial therapy acting on adhering stationary-phase
      microorganisms. In chronic osteomyelitis, orthopedic and plastic- reconstructive
      surgery is combined in the same procedure or within a short time span. In this
      article, pathogenesis, classification, diagnosis, and treatment of infections
      associated with intramedullary nails, external-fixation pins, plates, and screws
      are reviewed.

PMID- 16651074
TI  - Surgical aspects of infection involving osteosynthesis implants: implant design
      and resistance to local infection.
AB  - Infection is still a major complication associated with surgery in orthopedics
      and traumatology. The implant design, the implant material, and the implantation
      technique may play essential roles in preventing infection. The goal of this
      paper is to discuss a series of experiments evaluating different aspects of both
      surgical procedures and implants. For this purpose, standardized local
      application of the human pathogen Staphylococcus aureus was performed in an
      animal model. Although these experimental results may be clinically relevant,
      direct extrapolation to clinical infection rates should be avoided.

PMID- 16651075
TI  - Antibiotics in trauma and orthopedic surgery -- a primer of evidence-based
      recommendations.
AB  - Systematic reviews and meta-analyses published in recent years have allowed
      drafting of evidence-based guidelines for antibiotic prophylaxis in orthopedic
      and trauma surgery. It is important to recognize the limitations of the
      recommendations derived from the available body of evidence. Since some of the
      most relevant randomized controlled clinical trials were performed more than 20
      years ago, it is sometimes difficult to apply the data to today's clinical
      practice. In establishing consensus guidelines, it could prove difficult to
      identify areas for improvement through further research and better compliance.
      Although recommendations for optimized treatment of orthopedic implant infections
      are not currently based on first-class evidence, there are very promising new
      concepts emerging in this field, and we are awaiting more data and decisive
      conclusions from larger clinical trials.

PMID- 16651076
TI  - Antibacterial coating systems.
AB  - The local application of antibiotics is a well-known procedure that has been in
      successful clinical use for more than 20 years. The most frequently used carrier
      substance for the antibiotic or other antibacterial substances is
      polymethylmethacrylate (PMMA). However, because PMMA is not resorbable, as much
      as 70% of the antibiotic dose is permanently sequestered in the PMMA cement and
      therefore not available to combat bacterial colonization. Antibacterial coatings
      of metal implants represent an attractive solution to simplify the local
      application of an antibacterial substance in fracture care. Several coating
      technologies have been investigated, involving different carrier materials as
      well as different antibacterial substances. A fully resorbable coating containing
      gentamicin sulphate has yielded promising results in animal studies and
      intramedullary tibial nails with this coating have already been implanted
      successfully in a few patients. In the future, the main developmental focus for
      antibacterial coatings for implants will lie in tailoring the release
      characteristics and the antibacterial substance to minimize the risk of breeding
      resistant bacterial strains while maximizing the efficacy of the coating.

PMID- 16651077
TI  - Principles of systemic antimicrobial therapy in foreign material associated
      infection in bone tissue, with special focus on periprosthetic infection.
AB  - Foreign material associated infection in bone tissue is mostly characterized by
      the features of sessile pathogens acting from the foreign material surface. These
      bacteria protected by biofilm attached to the surface are highly resistant for
      antimicrobial agents and host's own defense as well. Therapy is based on surgical
      revision, with removal of the foreign material and supplementary antimicrobial
      therapy. Empirical antimicrobial therapy cannot be recommended unless life
      threatening septicemia occurs. Infected bone tissue is lower compartment with
      respect to antimicrobial chemotherapy. Therefore, antibiotics must be
      administered in high dosage for an extended period of time. It is almost
      impossible to eradicate these pathogens by antibiotics alone even though the
      clinical symptoms may be influenced. The options of antimicrobial therapy are: 1.
      Antibiotics alone: Only suppression of clinical symptoms. 2. Amputation or
      resection arthroplasty in combination with antibiotics: The results are fair but
      poor in function. 3. Surgical revision with retention of the foreign material and
      long-term antibiotic therapy including rifampicin: This procedure is possible in
      early, not yet established foreign material infections. 4. Treatment of the
      periprosthetic infection: Surgical revision with exchange of the prosthesis
      combined with systemic (and optional local) therapy, regardless whether the
      revision is performed in 1 - or multiple-stages. Treatment of these infections
      should be carried out in specialized centers in cooperation with an experienced
      infectious disease specialist. Since most available data are empirical, further
      prospective studies are needed for evaluation of these therapeutic concepts.

PMID- 16651078
TI  - Prophylaxis and treatment of implant-related infections by local application of
      antibiotics.
AB  - Despite the improvement in surgical technique and implant design in orthopedic
      and trauma surgery, implant-related infections are still a challenging problem
      for surgeons. The use of local prophylaxis to avoid infection, such as antibiotic
      loaded cement in arthroplasty, gentamicin PMMA beads and gentamicin-collagen
      sponge in trauma surgery, and antibacterial coating of metal implants, is
      discussed in the first part of this article. The second part discusses the role
      of local antibiotics such as gentamicin PMMA beads, and gentamicin-collagen and
      antibiotic-loaded cement spacers in treating implant-related infections.

PMID- 16651154
TI  - Meniscus allograft survival in patients with moderate to severe unicompartmental
      arthritis: a 2- to 7-year follow-up.
AB  - PURPOSE: We present meniscus allograft survival data at least 2 years from
      surgery for 45 patients (47 allografts) with significant arthrosis to determine
      if the meniscus can survive in an arthritic joint. TYPE OF STUDY: Prospective,
      longitudinal survival study. METHODS: Data were collected for 31 men and 14
      women, mean age 48 years (range, 14 to 69 years), with preoperative evidence of
      significant arthrosis and an Outerbridge classification greater than II. Failure
      is established by previous studies as allograft removal. No patient was lost to
      follow-up. RESULTS: The success rate was 42 of 47 allografts (89.4%) with a mean
      failure time of 4.4 years as assessed by Kaplan-Meier survival analysis.
      Statistical power is greater than 0.9, with alpha = 0.05 and N = 47. There was
      significant mean improvement in preoperative versus postoperative self-reported
      measures of pain, activity, and functioning, with P = .001, P = .004, and P =
      .001, respectively, as assessed by a Wilcoxon rank-sum test with P = .05.
      CONCLUSIONS: Meniscus allografts can survive in a joint with arthrosis,
      challenging the contraindications of age and arthrosis severity. These results
      compare favorably with those in previous reports of meniscus allograft survival
      in patients without arthrosis. LEVEL OF EVIDENCE: Level IV.

PMID- 16651155
TI  - A prospective randomized comparison of spinal versus local anesthesia with
      propofol infusion for knee arthroscopy.
AB  - PURPOSE: Knee arthroscopy is the most common orthopaedic procedure performed in
      the United States, and there are few randomized studies comparing local
      anesthesia, in conjunction with propofol, with regional anesthesia for knee
      arthroscopy. The purpose of the study was to test the hypothesis that patients
      receiving local anesthesia combined with propofol infusion (LAP) will recover
      from anesthesia faster and experience less postoperative headache and back pain
      compared with spinal anesthesia (SA). TYPE OF STUDY: Randomized trial. METHODS: A
      randomized trial was used to compare SA and LAP in adults undergoing knee
      arthroscopy. A simple randomization scheme in sealed envelopes was used. An
      independent observer collected data the day of surgery and contacted patients by
      telephone on the first postoperative day to inquire about back pain or headaches,
      and to have them rate their anesthesia (excellent, good, fair, or poor). RESULTS:
      Eighteen patients (average age, 53 years) received LAP and 14 received SA.
      Baseline assessment of the 2 groups was similar. The mean time spent in the
      postoperative anesthesia care unit (PACU) was 2.8 hours for the LAP group and 4.0
      hours for the SA group (P < .0001). Spinal anesthesia was associated with back
      pain in 5 of 14 patients in the SA group compared with none in the LAP group (P =
      .004). There were no statistically significant differences between the 2 groups
      with respect to headache (P = .5) or overall patient satisfaction (P = .3). The
      amount of time required to administer anesthesia was similar between the 2 groups
      (P = .2). The number of patients requiring additional sedation intraoperatively
      was higher in the LAP group compared with the SA group, 9 of 18 and 1 of 14,
      respectively (P = .02). CONCLUSIONS: Although subjects receiving LAP were more
      likely to require additional sedation intraoperatively compared with the SA
      group, LAP was associated with significantly less time to home readiness as
      measured by time in the PACU. LEVEL OF EVIDENCE: Level I.

PMID- 16651156
TI  - Anterior horn tears of the lateral meniscus in soccer players.
AB  - PURPOSE: The purpose of this retrospective study was to define the clinical and
      arthroscopic characteristics of anterior horn tears of the lateral meniscus. TYPE
      OF STUDY: Case series. METHODS: Fourteen patients with mean age of 20.2 years
      were enrolled in this institutional review board-approved study. All patients
      were soccer players with tears of the anterior horn of the lateral meniscus. All
      patients underwent physical examinations, magnetic resonance imaging (MRI), and
      arthroscopic treatment. RESULTS: Common symptoms were a catching sensation in 10
      patients (71.4%), pain at squatting in 9 patients (64.3%), and sense of giving
      way and effusion, each in 7 patients (50%). Five patients (35.7%) had lateral
      joint-line tenderness. McMurray's test was positive in 6 (42.9%) and tears were
      diagnosed by MRI in 13 (92.8%) patients. Arthroscopic examination showed multiple
      longitudinal tears in the avascular white zone of the meniscus in 7 patients
      (50%). CONCLUSIONS: These data show that the McMurray test and joint-line
      tenderness had a low diagnostic value in diagnosing anterior horn tears of the
      lateral meniscus. MRI, however, had a high diagnostic value. Common arthroscopic
      findings included multiple longitudinal tears within the white zone of the
      anterior horn. LEVEL OF EVIDENCE: Level IV.

PMID- 16651157
TI  - Comparison of in vitro and in vivo complement activation by metal and
      bioabsorbable screws used in anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of the study was to evaluate the biocompatibility of
      polylactide (PLLA) screws in comparison with standard metal screws for fixation
      of the patellar tendon graft in human anterior cruciate ligament (ACL)
      reconstruction. METHODS: A total of 41 patients (22 women and 19 men) were
      prospectively randomized for the use of metal interference screws (20 patients)
      or biologically resorbable PLLA screws from Linvatec, Largo, FL (21 patients).
      Average age at the time of surgery was 26 years (15 to 51 y). Synovial fluid and
      plasma were collected preoperatively and after 6 weeks in both groups. Plasma was
      analyzed for C5a and synovial fluid, as well as for terminal SC5b-9 complement
      complex (TCC) and interleukin (IL)-8. At 1 year after surgery, serum was
      incubated with metal, PLLA, and no screws; this was followed by analysis of C5a
      after 1 and 6 hours of incubation. Inflammatory mediators were measured through
      enzyme-linked immunosorbent assay (ELISA). RESULTS: In the BioScrew group, 4
      patient samples showed high C5a concentration in synovial fluid after 6 weeks,
      but no statistically significant difference was observed between the 2 groups (P
      = .11). One patient in the BioScrew group had a high TCC value after 6 weeks, but
      no statistically significant difference was seen between the 2 groups (P = .20).
      In the in vitro study, no increased C5a generation was observed in sera incubated
      with a BioScrew or a metal screw compared with controls. CONCLUSIONS: No
      statistically significant difference was observed between the BioScrew and metal
      screw groups concerning C5a, TCC, and IL-8 formation. However, some patients in
      the BioScrew group showed elevated values. LEVEL OF EVIDENCE: Level II,
      prospective randomized trial.

PMID- 16651158
TI  - Simultaneous arthroscopic reconstruction of the anterior and posterior cruciate
      ligaments with autogenous hamstring tendons.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      simultaneous arthroscopic reconstruction of anterior cruciate ligament (ACL) and
      posterior cruciate ligament (PCL) with hamstring tendons. TYPE OF STUDY:
      Retrospective case series. METHODS: Twelve cases of combined ACL/PCL ruptures
      were reconstructed arthroscopically with hamstring tendons in 1 stage. The
      semitendinosus tendon of the injured leg was used for 4-stranded ACL
      reconstruction, and the semitendinosus tendon and gracilis tendon of the
      uninjured leg were used for 6- to 8-stranded PCL reconstruction. The patients
      were followed-up for 32 months on average. Function was evaluated according to
      the International Knee Documentation Committee (IKDC) and Lysholm scales.
      Anterior and posterior knee laxity were examined using the KT-1000 arthrometer.
      RESULTS: No patients showed knee extension limitation. Knee flexion was 143
      degrees +/- 3.7 degrees on average (range, 130 degrees to 150 degrees ). KT-1000
      examination showed that the side-to-side difference of overall anterior-posterior
      laxity at 70 degrees of flexion was 0 to 2 mm in 7 patients, 3 to 5 mm in 4
      patients, and 7 mm in 1 patient; the side-to-side difference of posterior sag at
      70 degrees of flexion was 0 to 2 mm in 9 patients and 3 to 4 mm in 3 patients;
      the side-to-side difference of anterior laxity at 25 degrees of flexion was 0 to
      2 mm in 8 patients, 3 to 5 mm in 3 patients, and 7 mm in 1 patient. The Lysholm
      score of the 9 chronic cases was 66.5 +/- 8.1 before surgery and 91.8 +/- 4.6 at
      the last follow-up (P < .01). According to the last IKDC evaluation, 7 patients
      (58.33%) were graded A, 4 patients (33.3%) B, and 1 patient (8.33%) C. Except for
      1 patient who complained of mild pain at the donor site of the contralateral
      healthy knee, no patients complained of donor-site morbidity or dysfunction of
      the healthy leg. CONCLUSIONS: Simultaneous arthroscopic reconstruction of the ACL
      and PCL with autogenous hamstring tendons is reliable for the restoration of knee
      stability. LEVEL OF EVIDENCE: Level IV.

PMID- 16651159
TI  - Endoscopic iliotibial band release for external snapping hip syndrome.
AB  - PURPOSE: The external snapping hip syndrome is caused by slippage of the
      iliotibial band over the greater trochanter. Most cases are treated
      conservatively but if this fails, open surgical treatment is commonly performed
      by Z-plasty or by creating a defect on the iliotibial band. We present a series
      of 11 hips that were surgically treated by an endoscopic technique. TYPE OF
      STUDY: Prospective consecutive series of patients. METHODS: Diagnosis of external
      snapping hip syndrome was clinical in all cases and anteroposterior pelvis
      radiographs were taken to evaluate the hip joint. Endoscopic release was
      performed with the patient in the lateral decubitus position without traction
      using 2 portals, the superior trochanteric and inferior trochanteric. A standard
      4-mm, 30 degrees arthroscope was introduced at the inferior trochanteric portal
      over the iliotibial band. A needle was placed at the proximal trochanteric portal
      and visualized endoscopically. The portal was then established and subcutaneous
      tissue resection was performed with radiofrequency (RF) probes and a shaver until
      the iliotibial band was identifiable and released with a vertical cut made using
      an RF hook probe. The arthroscope was introduced into the space created under the
      iliotibial band and a transverse cut at the middle of the vertical release was
      then made, creating a cross-shape. Next the 4 resulting flaps were resected to
      make a diamond-shaped defect. RESULTS: Between September 2001 and December 2003,
      we treated 11 patients, 9 female (1 bilateral) and 1 male with an average age of
      26 years, for external snapping hip syndrome using an endoscopic technique. At an
      average 2-year follow-up, we had 1 patient with nonpainful snapping. The rest of
      the patients in the series had no complaints and returned to their previous level
      of activity. CONCLUSIONS: We present a reproducible endoscopic technique for the
      treatment of external snapping hip syndrome. Our results are comparable to those
      reported for open procedures. LEVEL OF EVIDENCE: Level IV.

PMID- 16651160
TI  - Arthroscopic visualization of the posterior subtalar joint in the prone position:
      a cadaver study.
AB  - PURPOSE: Subtalar arthroscopy in the prone position is thought to allow broader
      access to the posterior aspect of the joint than in the standard supine or
      lateral position. This study is aimed to assess if using the posteromedial (PM)
      portal in the prone position can increase the working area available through the
      dorsal and ventral posterolateral (PL) portals commonly used in the standard
      techniques. TYPE OF STUDY: In vitro cadaver study. METHODS: Six below-knee
      cadaver specimens were subjected to experimental arthroscopy on the posterior
      subtalar joint in a simulated prone position. On both the talar and calcaneal
      surfaces, the working areas (the maximal extent available to a working instrument
      while preserving surrounding cartilage) for the PL portals and the PM portal were
      identified. The combined area was compared with the area available from the PL
      portals alone, to assess the area extended with the PM portal. RESULTS: The talar
      working areas provided by the PL portals and PM portal were 31% +/- 13% and 26%
      +/- 8% of the total articular surface, respectively. The combined working area
      (43% +/- 13%) was greater than the PL working area alone; use of the PM portal
      increased the working area by a factor of 1.45. The calcaneal working areas from
      the PL and PM portals were 25% +/- 11% and 20 +/- 7%, respectively. The combined
      working area (35% +/- 14%) was similarly increased by a factor of 1.46 using the
      PM portal compared with PL portals alone (P < .05). CONCLUSIONS: In prone
      subtalar arthroscopy, significant extension of the working area was found by
      adding the PM portal to the standard PL portals, on both the talar and calcaneal
      surfaces. CLINICAL RELEVANCE: The PM portal that can be used in the prone
      position has a potential to increase the arthroscopic working area in the
      posterior subtalar joint.

PMID- 16651161
TI  - Arthroscopic distal clavicle resection: a comparison of bursal and direct
      approaches.
AB  - PURPOSE: To test the hypothesis that the direct (superior) approach to
      arthroscopic distal clavicle resection is as safe and effective as the bursal
      (subacromial) approach. METHODS: All patients who had an arthroscopic distal
      clavicle resection in our institution between 1994 and 2002 were reviewed.
      Patients with a history of acromioclavicular joint (ACJ) instability, previous
      shoulder surgery, glenohumeral pathology, full-thickness rotator cuff tear, or
      other significant orthopaedic comorbidity were excluded. Outcome data were
      collected including the American Shoulder and Elbow Surgeons (ASES) score as well
      as subjective ratings of pain and instability. RESULTS: Follow-up was completed
      on 66 shoulders of 60 patients. Twenty-four shoulders had a bursal approach
      (group I) and 42 had a direct approach (group II). There were 45 men and 15 women
      with an average age of 46 years (range, 21 to 78 years). Follow-up averaged 6.0
      years (range, 2 to 11.5 years). The average ASES score was 90 (range, 53-100) in
      group I and 94 (range, 55-100) in group II. Four patients (10%) in group II
      required reoperation: 2 patients required ACJ stabilization at 6 and 9 months
      postoperatively because of anteroposterior instability, and 2 patients required
      resection again at 5 years because of recurrent symptoms. CONCLUSIONS: Both the
      direct and bursal approaches lead to satisfactory outcomes in the majority of
      patients with ACJ arthrosis. However, the direct approach to the ACJ may damage
      the superior capsular ligaments, potentially leading to distal clavicle
      instability. Care should be taken when performing the direct ACJ resection to
      avoid disrupting the capsular restraints. LEVEL OF EVIDENCE: Level IV therapeutic
      case series.

PMID- 16651162
TI  - Arthroscopic treatment of chronically painful calcifying tendinitis of the
      supraspinatus tendon.
AB  - PURPOSE: The purpose of this study was to analyze the outcome of arthroscopic
      removal of calcifying tendinitis of the rotator cuff, to document the
      postoperative pain evolution, and to analyze structural changes of the
      supraspinatus tendon by use of ultrasonography. METHODS: Fifty-four of 58
      patients with a mean age of 45.4 years (+/-8 years) enrolled in the study were
      available for follow-up. The calcific deposits were exclusively located in the
      supraspinatus tendon. Shoulder function was evaluated by using the Constant
      score. Radiographs were obtained preoperatively, immediately postoperatively, and
      at 3, 6, 12, and 24 months. The integrity of the rotator cuff was assessed by
      using ultrasonography. RESULTS: Shoulder function according to the Constant score
      improved from 32.8 points (+/-19.8) preoperatively to 90.9 (+/-13.0) at 24 months
      (P < 0.001). The evolution of postoperative pain was very irregular; 31% of the
      patients were pain free or reached their minimum pain level after 3 months, 17%
      after 6 months, 20% after 9 months, and 28% after 12 months; 78% of the patients
      returned to work within 6 weeks, irrespective of their profession. At the final
      follow-up 92% of the patients were very satisfied with the outcome.
      Ultrasonography revealed minor structural changes of the supraspinatus tendon in
      66% of the patients. CONCLUSIONS: The study confirmed previously reported
      successful results of arthroscopic treatment of calcifying tendinitis of the
      rotator cuff. Complete intraoperative removal of the deposit did not appear to be
      essential. Even if most of the patients were able to return to work within 6
      weeks, postoperative recovery was prolonged over several months in most of the
      patients. The clinical relevance of the ultrasonographic changes of the
      supraspinatus tendon has not yet been determined. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 16651163
TI  - Volume analysis of arthroscopic capsular shift.
AB  - PURPOSE: To determine how much volume reduction can be obtained with varying
      amounts of arthroscopic capsular plication. METHODS: Six fresh-frozen, cadaveric
      specimens were used. Specimens were rejected if a rotator cuff tear was present.
      The volume of each shoulder joint was measured under 3 conditions: no capsular
      shift, 5-mm capsular shift, and 10-mm capsular shift. For each shift, 4 sutures
      were placed arthroscopically, 2 anteriorly and 2 posteriorly. Repeated measures
      were used to confirm the validity of the measurements. Data were analyzed with
      parametric and nonparametric tests. RESULTS: The average percentage of volume
      reduction at 5 mm of capsular plication from control was 16.2% (range, 9.7% to
      21.5%). The percentage of volume reduction from control to 10 mm of capsular
      plication averaged 33.7% (range, 25.3% to 44.6%). Statistical significance was
      found with both parametric (P < .0001) and nonparametric tests (P < .0313).
      CONCLUSIONS: The current study found that capsular volume reduction was related
      to the amount of capsular plication with reproducible results. Capsular plication
      can produce volume reduction comparable to other techniques. CLINICAL RELEVANCE:
      The data could be used to determine the potential number of sutures and amount of
      tissue plication needed for the amount of laxity found at surgery.

PMID- 16651164
TI  - Tendon augmentation grafts: biomechanical failure loads and failure patterns.
AB  - PURPOSE: The purpose of this study was to determine the load to failure strengths
      and modes of failure of various commercially available tendon augmentation
      xenografts and allografts. TYPE OF STUDY: Experimental laboratory study. METHODS:
      GraftJacket (Wright Medical Technology, Arlington, TN), CuffPatch (Arthrotek,
      Warsaw, IN), Restore (Depuy, Warsaw, IN), Permacol (Tissue Science Laboratories,
      Covington, GA; licensed to Zimmer, Warsaw, IN), and TissueMend (TEI Biosciences,
      Boston, MA; licensed to Stryker Howmedica Osteonics, Kalamazoo, MI) measuring 2 x
      5 cm were hydrated according to manufacturers guidelines, a horizontal mattress
      stitch 5-mm wide was placed 5 mm from the narrow edge of the graft. Tensile loads
      to failure were applied on the suture while an Instron machine held the graft
      material and mean loads to failure of the suture graft construct were obtained
      and modes of graft failure noted. RESULTS: The mean loads to failure were
      obtained: GraftJacket thin (157 N), GraftJacket MaxForce (182 N), GraftJacket
      Extreme (229 N), CuffPatch (32 N), Restore (38 N), Permacol (128 N), and
      TissueMend (70 to 76 N). Failure occurred principally by suture pull-through in
      all specimens and patterns tended to vary by implant type. CuffPatch and
      TissueMend tended to fail by isthmus pullout, whereas Restore and Graft jacket
      failed by end pullout. The tissues were statistically stratified into four groups
      depending on the material. Human skin (GraftJacket) was the strongest followed by
      porcine skin (Permacol) and bovine skin (TissueMend). Both in turn were stronger
      than the porcine small intestine submucosa (Restore and CuffPatch) (P < 0.001).
      CONCLUSIONS: Suture retention can be reliably tested with a narrow range of
      standard error utilizing this testing methodology. Skin has higher loads to
      failure than intestine submucosa. Failure modes differed significantly among the
      implant types, suggesting that suturing methods for each implant should be
      considered independently before use. These data cannot be interpreted to suggest
      that one graft material is clinically superior to another. Rather, each has
      different properties that the surgeon should recognize when considering their
      use. CLINICAL RELEVANCE: These grafts have been used as augmentations and
      substitutions in tendon repairs and as a material for interpositional
      arthroplasty. These data show that the successful use of these materials requires
      adequate separation of the fixation sutures and provides an understanding of how
      each material will fail if subjected to excessive loading during the
      rehabilitation period.

PMID- 16651165
TI  - Arthroscopic anterior stabilization and posterior capsular plication for anterior
      glenohumeral instability: a report of 71 cases.
AB  - PURPOSE: Results after arthroscopic treatment of anterior glenohumeral
      instability continue to improve as advancements are made in instrumentation and
      techniques. We present 71 cases of anterior glenohumeral instability treated with
      arthroscopic anterior stabilization and posterior capsular plication. TYPE OF
      STUDY: Case series. METHODS: Arthroscopic anterior reconstruction and posterior
      inferior "pinch-tuck" capsular plication was performed in 71 shoulders (67
      patients) with anterior glenohumeral instability. The average follow-up was 33.3
      months (range, 20 to 24 months). Outcomes were assessed by completion of the
      Simple Shoulder Test (SST), Western Ontario Shoulder Instability (WOSI) Index, a
      Rowe score, and a subjective self-assessment shoulder instability form. RESULTS:
      Postoperative dislocation occurred in 5 patients (7%). The average SST score was
      11.2 (12 maximum) and the average WOSI Index was 85.6% (range, 30.6% to 100%).
      The average Rowe score was 85. Ninety-seven percent of patients reported they
      were able to return to their normal activity level, and 90% of patients reported
      that they were able to return to their previous level of athletics; 100% of
      patients reported that they were doing better than before surgery and were
      satisfied with their result; 100% of patients reported that they would undergo
      the procedure again. CONCLUSIONS: Arthroscopic anterior stabilization using
      suture anchors, combined with posterior capsular suture plication, is a reliable
      treatment option for anterior glenohumeral instability. LEVEL OF EVIDENCE: Level
      IV.

PMID- 16651166
TI  - Treatment of patients with spinoglenoid cysts associated with superior labral
      tears without cyst aspiration, debridement, or excision.
AB  - PURPOSE: To describe a case series of 10 consecutive patients with spinoglenoid
      cysts and associated superior labral tears treated by labral repair performed by
      the same surgeon without formal cyst aspiration, debridement, or excision.
      METHODS: Ten patients with spinoglenoid cysts and associated superior labral
      tears demonstrated on preoperative magnetic resonance imaging (MRI) were
      retrospectively reviewed. Evidence of weakness on examination was further
      evaluated through nerve conduction studies. All 10 patients underwent surgical
      repair of the labral tear performed by the same surgeon without formal cyst
      aspiration, debridement, or excision. Postoperatively, detailed shoulder and
      neurologic examinations were performed, and follow-up nerve conduction studies
      and MRIs were obtained. RESULTS: Ten patients were evaluated clinically at a mean
      of 10.2 months after surgical repair (range, 6 to 27 months). In all, 8 males and
      2 females of average age 47.7 years (range, 35 to 56 years) were studied.
      Preoperative examination revealed that 6 patients had external rotation weakness.
      Nerve conduction studies performed in these 6 patients confirmed suprascapular
      neuropathy in 4 of them. Labral repair without formal cyst excision resulted in
      successful outcomes for all 10 patients after spinoglenoid cysts associated with
      superior labral tears had been diagnosed. All 4 patients with suprascapular
      neuropathy recovered strength and demonstrated normal nerve conduction studies
      postoperatively. In 8 of 10 patients, MRIs performed postoperatively demonstrated
      complete resolution of the cyst, along with labral healing. All patients were
      able to return to work with no restrictions on activities, and all were satisfied
      with their outcomes. CONCLUSIONS: This study demonstrated successful clinical,
      electromyographic, and MRI outcomes for patients with spinoglenoid cysts and
      superior labral tears, who were treated by labral repair without formal cyst
      excision. Treatment given for intra-articular disease is the key component of
      surgical management. LEVEL OF EVIDENCE: Level IV, case series study.

PMID- 16651167
TI  - Monopolar radiofrequency electrothermal shrinkage of the scapholunate ligament.
AB  - PURPOSE: This study examined whether radiofrequency electrothermal shrinkage has
      a role in the treatment of patients with symptomatic dynamic and predynamic
      scapholunate (SL) instability without advanced degenerative changes. METHODS:
      From January 1999 to July 2001, 19 wrists with laxity of the SL ligament, but
      with symptomatic instability, were treated with arthroscopic electrothermal
      shrinkage of the SL ligament using a monopolar radiofrequency probe. Before
      surgery, all patients underwent wrist arthroscopy to confirm the diagnosis and
      exclude arthritis. The sample included 16 men and 3 women with an average age of
      23.3 years (range, 18 to 27 years). The average time from injury to operation was
      17.2 months (range, 14 to 28 months). All patients underwent follow-up at our
      clinic regularly for an average of 28.1 months (range, 24 to 34 months). RESULTS:
      All 19 patients had attenuation or laxity of the continuity SL ligament in the
      radiocarpal joint. Modified Mayo wrist scores revealed the following
      functionality: the total arc of wrist motion in the flexion-extension plane loss
      averaged 5.1 degrees (P > .01). Grip force improved significantly, with 14.7%
      improvement of that on the normal side (P < .01). The Wilcoxon signed-rank test
      was used to compare the results: the postoperative scores were significantly
      better than the preoperative scores (P < .01). Fifteen patients (79%) were fully
      satisfied with the results and returned to their preinjury activity. Four
      patients (21%) had recurrent laxity of the SL joint. CONCLUSIONS: Electrothermal
      shrinkage of the SL ligament in patients with symptomatic, predynamic and dynamic
      SL instability had a 79% success rate at a minimum of 2 years' follow-up. LEVEL
      OF EVIDENCE: Level IV, case series.

PMID- 16651168
TI  - Bone tumors around the knee: risks and benefits of arthroscopic procedures.
AB  - Although most primary bone tumors and soft tissue tumors arise around the knee
      joint, many patients with tumoral conditions attribute their symptoms to
      traumatic events. This may lead to misdiagnosis and mistakes in selection of
      therapeutic approach. Arthroscopy is the preferred method for diagnosis and
      treatment of knee joint disease, but even a minimally invasive procedure may have
      adverse consequences in the presence of an unsuspected neoplasm. Thus, evaluation
      of all patients who may benefit from knee arthroscopy requires a careful and
      systematic workup that consists of appropriate noninvasive imaging studies and
      thoughtful consideration regarding the need for magnetic resonance imaging.
      Arthroscopic biopsy and treatment are recommended for selected intra-articular
      tumors. In addition, arthroscopy is a useful adjunct during surgical treatment of
      patients with certain juxta-articular benign bone tumors. In this Current
      Concepts review, we consider the risks and benefits of arthroscopy in the
      presence of tumors about the knee joint.

PMID- 16651169
TI  - Arthroscopic transosseous suture anchor technique for rotator cuff repairs.
AB  - The skin is incised 1 to 2 cm distal to the lateral portal. A transosseous tunnel
      is created through the greater tuberosity by a sharp penetrator, entering 1.5 to
      2 cm distal to the top of the greater tuberosity. The penetrator exits medially,
      between the tip of the greater tuberosity and the articular surface of the
      humeral head, in the middle of the footprint. The first anchor, a 5-mm Spiralok
      (DePuy Mitek, Norwood, MA) is placed at the penetrator's exit site on the
      footprint. Using a specially designed suture leader, the lateral limb of the
      suture in the anchor, which passes through the previously created transosseous
      tunnel, is taken from the anchor and pulled out. The other suture end is passed
      through the supraspinatus tendon. The second suture, placed superficially in the
      anchor, is passed from the anchor through the supraspinatus tendon, as a mattress
      suture. If more anchors are required, the procedure should be repeated. The
      transosseous suture limb and the suture limb that is passed through the
      supraspinatus tendon are tied through the lateral portal. The knot tying is then
      performed with a sliding Delimar knot. The mattress suture, passing through the
      supraspinatus tendon, is tied through the anterior lateral portal. The knot tying
      procedure is repeated depending on the number of anchors.

PMID- 16651170
TI  - ISOCAN method and device for arthroscopic suture management.
AB  - ISOCAN refers to a method and device that functionally isolates sutures within
      the working cannula during arthroscopic rotator cuff repair, allowing passage of
      instruments through the same cannula through an instrument-passing quadrant. As
      sutures are passed, tension and orientation are maintained with each limb by
      parking each limb into a suture-holding slot. Suture tension prevents loops from
      forming and functionally isolates each limb. Attention to detail as the sutures
      are passed, keeping track of the cuff limb and the lateral limb, and parking them
      in sequence, prevents tangles. The instrument-passing quadrant is kept clear by
      parking sutures in only 3 of the 4 quadrants around the ISOCAN. Advantages extend
      beyond suture management and include the ability of an ISOCAN ring to hold
      reduction tension on the cuff edge, spreading the reduction force over multiple
      points of fixation, allowing individual suture pairs to be tied down without
      tension. This enhances knot security and loop security. The technique is
      especially helpful in arthroscopic rotator cuff repair but can be used wherever
      arthroscopic suture management is needed, including arthroscopic Bankart repairs
      and SLAP lesion repairs. A do-it-yourself ISOCAN may be constructed
      intraoperatively using an 8.25-mm Arthrex clear screw in cannula with a no-spray
      stopper (Arthrex, Naples, FL). Radial cuts can be made in the no-spray stopper to
      serve as ISOCAN suture parking slots. A metal ISOCAN ring prototype has been
      adapted to press-fit over this same cannula and has been used to great advantage
      in over 100 arthroscopic rotator cuff repairs by the author.

PMID- 16651171
TI  - Repair of the adult acetabular labrum.
AB  - Although hip arthroscopy is a new technique, indications for its use are rapidly
      expanding. With better utilization and understanding of both radiologic
      assessment of hip pathology and clinical examination, specific intra-articular
      derangement is being identified. Longitudinal, peripheral, and intrasubstance
      anterior hip labral tears can be repaired using anterior paratrochanteric and
      anterior portals with standard hip arthroscopy equipment. Repair of the torn
      labrum may help re-establish the anatomic function of the labrum, thereby
      preventing biomechanical compromise through surgical debridement, which may lead
      to degenerative changes associated with osteoarthritis. Although long-term
      results are still unknown, results of short-term follow-up are positive.

PMID- 16651172
TI  - Meniscus transplantation using the femoral distractor.
AB  - Accurate tunnel placement, graft passage, and secure suture fixation are key
      elements in meniscus allograft transplantation. We describe the use of a femoral
      distractor in meniscus transplantation. Joint distraction on the side of the
      transplantation by the femoral distractor can dramatically improve visibility and
      joint access. The distractor is applied after all necessary preparatory work. The
      distal femoral pin is placed in the supracondylar region on the side
      corresponding to the side to be transplanted. To avoid injury to the peroneal
      nerve, the proximal tibial pin is placed medial to lateral for both medial and
      lateral transplantations. The tibial pin is placed at a level approximately 1 to
      2 cm below the tibial tubercle. The knee is then held in the flexion angle that
      affords the best visualization arthroscopically (typically between 60 degrees and
      90 degrees of flexion). Gradual distraction is then applied with the distraction
      rod until adequate visualization is obtained. The case then proceeds with tunnel
      or trough creation, graft delivery, and peripheral repair. The improved
      visualization and access provided by the femoral distractor markedly simplifies
      the more challenging aspects of meniscus transplantation, helping to ensure
      precise tunnel placement, facilitate graft passage, and aid in accurate suturing.

PMID- 16651173
TI  - Arthroscopic treatment of glenoid fractures.
AB  - The patient was placed in the lateral decubitus position. The arthroscope was
      introduced through the posterior approach. The probe hook was introduced through
      a working cannula through the anterosuperior portal performed in an inside-out
      technique. The mobilization possibilities of the osteochondral fragments were
      then assessed. The use of a shaver was always necessary to clean the fracture
      site and evacuate clots. A nonabsorbable suture was passed through the labrum and
      the capsule tissue of the displaced articular fragment in its superior edge. The
      first suture was used as a traction stitch and allowed replacing the fragment in
      its original position and maintaining it during the placement of others sutures.
      A hole was made in the anterosuperior edge of the nonfractured glenoid and then a
      long drill was passed backward according to the transglenoid suture technique of
      Caspari or Morgan. Stitches were passed through the glenoid to the infraspinatus
      fossa. When articular congruity was judged satisfactory, the stitches were tied
      on the fascia of the infraspinatus muscle. The patients were immobilized in a
      sling for 3 weeks.

PMID- 16651174
TI  - Arthroscopic technique of interposition arthroplasty of the glenohumeral joint.
AB  - Arthroscopic glenohumeral interposition arthroplasty is performed with the
      patient placed in the lateral decubitus position. Standard posterior, anterior,
      and anterosuperior portals are created, a routine diagnostic arthroscopy is
      performed, and the joint is debrided with the use of an arthroscopic shaver. An
      arthroscopic burr is used to resect prominent osteophytes, to alter the version
      of the glenoid if necessary, and to create microfractures on the glenoid surface.
      Next, 3 absorbable sutures are passed percutaneously with a 30 degrees angled
      suture grasper from 3 different sites posteriorly through the posterior capsular
      labral tissue and into the anterior portal cannula, where they are isolated by
      means of the suture saver kit. The prepared interposition membrane/tissue
      (GRAFTJACKET Regenerative Tissue Matrix, Wright Medical Technology, Inc.,
      Arlington, TN) is tagged with the 3 sutures in the anterior cannula before it is
      introduced into the joint. Three additional sutures are attached to the membrane
      anteriorly at 1, 3, and 5 o'clock positions and are isolated with suture savers.
      The membrane is next introduced into the joint through the anterior cannula and
      is aligned with the glenoid rim. The anterior sutures are rerouted through the
      anterior capsular-labral tissue with a 70 degrees angled suture grasper, and they
      are retrieved through the anterior cannula. Intra-articular nonsliding knots are
      used anteriorly to anchor the interposition tissue to the anterior glenoid labrum
      and capsule. The posterior sutures are knotted intra-articularly, or they may be
      tied extra-articularly; the proximal and distal posterior sutures are retrieved
      subcutaneously out through the skin tract of the posterior portal and are knotted
      with the suture present in this portal, with the use of nonsliding knots.
      Stability of the interposition tissue is assessed by movement of the glenohumeral
      joint through its entire range of motion. The postoperative protocol consists of
      early passive exercises, active exercises after 3 weeks, and muscle-strengthening
      exercises after 6 weeks.

PMID- 16651175
TI  - New hamstring fixation technique for medial collateral ligament or posterolateral
      corner reconstruction using the mosaicplasty system.
AB  - In this study, we describe a new hamstring fixation technique with a bone graft
      using the Mosaicplasty system for the reconstruction of the medial collateral
      ligament (MCL) or posterolateral corner (PLC) of the knee. In this technique, a
      cylindrical bone plug (6.5 mm in diameter, 15 mm in length) is harvested from the
      anatomical femoral attachment of the MCL or popliteal tendon using the
      Mosaicplasty system. After placing the autologous semitendinosus or gracilis
      tendon as a graft in the created bone socket, the bone plug is replaced over the
      graft. The graft is secured with a spike staple after appropriate tension is
      applied to the graft. This fixation technique can provide rigid and less invasive
      fixation, because the distance between the fixation sites can be shorter than
      that in the Endobutton technique. Compared to fixation with only a staple with no
      bone graft, the bone graft may enhance tendon to bone healing.

PMID- 16651176
TI  - Arthroscopic all-inside lateral meniscus suture using posterolateral portal.
AB  - A new arthroscopic all-inside suture for lateral meniscus posterior horn tear
      using a single posterolateral portal is described. A lateral meniscus posterior
      horn peripheral longitudinal tear is often seen with anterior cruciate ligament
      injury or discoid lateral meniscus tear. Conventional repair methods, such as
      arthroscopic inside-out, outside-in, or all-inside sutures, can be cumbersome and
      technically demanding. Our all-inside suture using the posterolateral portal
      allows thorough visualization of the posterolateral structures, excellent
      coaptation of torn meniscus, strong knot tightening, and avoidance of inadvertent
      cartilage injury. The arthroscope is inserted through the anteromedial portal and
      reaches the posterolateral compartment by a transcondylar approach. A suture hook
      is introduced into the posterolateral portal without a cannula, penetrates
      posterior peripheral rim, crosses the tear, and passes through mobile torn
      fragment. A large amount of No. 0 PDS is passed, so that it curls up inside the
      joint. After the suture hook is removed, a suture retriever is inserted through
      the posterolateral portal to pull out 2 ends of the PDS at the same time. The
      retrieved suture ends are passed through a knot pusher and a 5.5-mm cannula is
      introduced over the retrieved suture materials for the SMC knot to be tied. A
      longitudinal tear of lateral meniscus posterior horn is repaired with 2 to 3
      sutures.

PMID- 16651177
TI  - Variation in the length of the tibial tunnel in anterior cruciate ligament
      reconstruction: is it safe to use a 35-mm screw?
AB  - Tibial fixation is the key to success in anterior cruciate ligament (ACL) surgery
      using the hamstring tendon technique. Interference screws are popular intratunnel
      fixation devices not exceeding 35 mm in length. A mismatch between the lengths of
      the tibial tunnel and the interference screw can cause protrusion of the screw
      inside the knee or outside the anterior tibia, with a poor postoperative outcome.
      Our objective was to evaluate the safety length that exists with the use of a 35
      mm screw in the tibial tunnel. For this purpose, 27 patients with ACL
      reconstruction were included. All measurements were performed directly during
      surgery. The lengths were recorded along with the patients' data. Our study group
      included 16 male and 11 female patients with an average age of 30.9 years. The
      average tibial tunnel length was 43.4 mm (range, 40 to 48 mm). This means that
      for a tibial tunnel drilled at a 55 degrees angle, its length will be at least 5
      mm longer than the 35-mm screw. In the same way, the distance between the graft
      fixation and the articular surface will not exceed 13 mm if the screw is
      completely inside the tunnel.

PMID- 16651178
TI  - Arthroscopically assisted reduction of a lateral femoral notch in acute tear of
      the anterior cruciate ligament.
AB  - We report the case of a 20-year-old soccer player who suffered a tear of the
      anterior cruciate ligament with a depression fracture of the lateral femoral
      condyle. In addition to repairing the ligament we were able to arthroscopically
      reduce the depression fracture using a bioabsorbable screw. We tamped the
      surrounding cancellous bone with dilatators and chisels to create a bearing for
      an interference screw. This prepared for the placing of the screw and resulted in
      a sufficient reshaping of the condyle. We then inserted a threaded bioabsorbable
      interference screw into the lateral condyle under arthroscopic guidance to reline
      the fracture and reduce joint incongruity. Postoperative magnetic resonance
      imaging showed a significant reduction of the fracture.

PMID- 16651179
TI  - Radial displacement of lateral meniscus after partial meniscectomy.
AB  - Radial displacement or extrusion of the meniscus has been reported as a
      complication after meniscal transplantation and is sometimes observed in knees
      with advanced osteoarthritis. In this report, the case of a patient with radial
      displacement of the lateral meniscus after partial meniscectomy is presented. He
      had an incomplete discoid lateral meniscus with an anterior horn tear. The inner
      portion of the lateral meniscus was excised to leave a width of 8 to 10 mm.
      However, follow-up magnetic resonance imaging showed radial displacement of the
      mid-body of the lateral meniscus and a compatible finding of chondromalacia of
      the lateral compartment of the knee.

PMID- 16651180
TI  - Tissue engineering techniques for the treatment of a complex knee injury.
AB  - We report and discuss the use of and rationale for tissue engineering techniques
      in a 40-year-old sportsman who suffered simultaneous anterior cruciate ligament
      (ACL) rupture, irreparable medial meniscal tear, and chondral lesion of the
      medial femoral condyle. A 2-step treatment was adopted to address all lesions.
      The first procedures consisted of ACL reconstruction and collagen meniscus
      implant (CMI), followed 6 months later by autologous chondrocyte implantation on
      a collagen membrane (MACI). A CMI biopsy was performed 6 months after
      implantation. Histologic and ultrastructural analysis documented scaffold
      invasion by cells and newly synthesized connective tissue. At 2-year follow up,
      the clinical and functional results were good and magnetic resonance imaging
      showed integration of the meniscal and cartilage implants. In this patient, each
      lesion needed to be addressed to achieve an optimal outcome. The primary goal was
      to restore normal joint biomechanics by performing CMI and ACL reconstruction.
      MACI was an adequate solution for the management of the large (5 cm(2)) chondral
      defect.

PMID- 16651181
TI  - Ulnar nerve palsy after elbow arthroscopy.
AB  - Reports of ulnar nerve injury as a result of elbow arthroscopy are rare in the
      literature. We report a case of ulnar nerve injury following arthroscopic
      debridement and retrograde drilling of the capitulum in a patient with
      symptomatic osteochondritis dissecans. The standard location of proximal medial
      portal placement is 2 cm proximal to the medial epicondyle at the level of the
      medial intermuscular septum. In this location, the ulnar nerve is protected from
      injury by the medial intermuscular septum. Extending this placement more
      proximally may negate this protection, leaving the nerve more susceptible to
      injury.

PMID- 16651183
TI  - Ulnar collateral ligament of the elbow.

PMID- 16651184
TI  - Anopheles gambiae lipophorin: characterization and role in lipid transport to
      developing oocyte.
AB  - Lipid transport in arthropods is achieved by highly specialized lipoproteins,
      which resemble those described in vertebrate blood. Here, we describe
      purification and characterization of the lipid-apolipoprotein complex, lipophorin
      (Lp), in the malaria vector mosquito Anopheles gambiae. We also describe the Lp
      mediated lipid transfer to developing eggs and the distribution of the imported
      lipid in developing embryos. The density of the Lp complex was 1.135 g/ml with an
      apparent molecular weight of 630 kDa. It is composed of two major polypeptides,
      apoLp I (260 kDa) and apoLp II (74 kDa) and composed of 50% protein, 48% lipid
      and 2% carbohydrate (w/w). Hydrocarbon, cholesterol, phosphatidyl choline,
      phosphatidyl ethanolamine, cholesteryl ester and diacylglyceride were the major
      Lp-associated lipids. Using fluorescently tagged lipids, we observed patterns
      that suggest that in live developing oocytes, the Lp was taken up by a receptor
      mediated endocytic process. Such process was blocked at low temperature and in
      the presence of excess unlabeled Lp, but not by bovine serum albumin. Imported Lp
      was segregated in the spherical yolk bodies (mean size 1.8 microm) and
      distributed evenly in the cortex of the oocyte. In embryonic larvae, before
      hatching, a portion of the fatty acid in vesicles was found evenly distributed
      along the body, whereas portion of phospholipids was accumulated in the
      intestine.

PMID- 16651185
TI  - Role of the transcriptional repressor mdGfi-1 in CYP6D1v1-mediated insecticide
      resistance in the house fly, Musca domestica.
AB  - Gfi-1 is a C(2)H(2)-type zinc finger protein that is a transcriptional repressor
      in vertebrates and has been implicated in control of CYP6D1 expression in house
      flies (Musca domestica). A 15 bp insert, which disrupts a putative mdGfi-1
      binding site in the CYP6D1v1 promoter has been implicated as a cause of increased
      expression of CYP6D1, and thus insecticide resistance. Using electrophoretic
      mobility shift assays we demonstrate that the CYP6D1 promoter from susceptible
      strains binds mdGfi-1. The 15 bp insert that interrupts the mdGfi-1-binding site
      in insecticide-resistant strains reduces the amount of mdGfi-1 binding by 9- to
      20-fold, consistent with the role of mdGfi-1 in resistance. Partial sequences of
      mdGfi-1 (spanning the first intron) from individual houseflies from 11 different
      strains revealed the presence of 23 alleles. There was no consistent difference
      in the mdGfi-1 alleles between susceptible and CYP6D1-mediated insecticide
      resistant strains, indicating that mdGfi-1 alleles were not likely involved in
      resistance. Polymorphisms were used to map mdGfi-1 to autosome 1. Quantitative
      real time PCR (qRT-PCR) revealed Gfi-1 expression was higher in the thorax
      compared to the head and abdomen, and varied between life stages and between
      strains. However, similar levels of mdGfi-1 were detected in susceptible and
      resistant adults suggesting that altered levels of mdGfi-1 were not likely a
      cause of insecticide resistance. The significance of these results to
      understanding insecticide resistance is discussed.

PMID- 16651186
TI  - Mutations in the acetylcholinesterase gene of Bactrocera dorsalis associated with
      resistance to organophosphorus insecticides.
AB  - Mutations in the gene encoding the enzyme acetylcholinesterase (AChE) of the
      oriental fruit fly, Bactrocera dorsalis, associated with resistance to an
      organophosphorus insecticide have been characterized. Three point mutations
      producing nonsynonymous changes in the predicted amino acid sequence of the
      product of the B. dorsalis ace gene in resistant vs. susceptible flies have been
      identified. One of these changes is unique to B. dorsalis while the other two
      occur at sites that are identical to mutations previously described for another
      Bactrocera species. Although the precise role of the third mutation is not
      clearly established, the independent origin of two identical alterations in these
      two species strongly supports the idea proposed previously that molecular changes
      associated with insecticide resistance in key genes and enzymes such as AChE are
      largely constrained to a limited number of sites. The results obtained here also
      suggest that the widespread use of organophosphorus insecticides will likely lead
      to a predictable acquisition of resistance in wild populations of B. dorsalis as
      well as other pest species. For surveys of B. dorsalis populations that may
      develop resistance, diagnostic tests using PCR-RFLP based methods for detecting
      the presence of all three mutations in individual flies are described.

PMID- 16651187
TI  - In vitro assay for sex pheromone biosynthesis by the female yellow mealworm
      beetle and identification of a regulated step.
AB  - Several pheromones are known to be involved in mediating the mating behavior of
      the yellow mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae). The
      only sex pheromone that has been identified to date in this species is the female
      produced male attractant, 4-methylnonanol (MNol). The objective of this study was
      to develop an in vitro assay for the last biosynthetic step involved in MNol
      biosynthesis, the reduction of 4-methylnonanoic acid (MNA) to the corresponding
      pheromone product. In vitro assays were conducted by adding appropriate cofactors
      and radioactively labelled precursor. Radioactive pheromone product was separated
      from the radioactive precursor by column chromatography, and quantified through
      scintillation counting. The conversion of MNA to MNol was observed, and was
      comparable to that observed in vivo using the same radiolabelled substrate. In
      both the in vivo and in vitro assays, the (3)H-MNA was also converted to a
      nonpolar product, tentatively identified as a triacylglyerol (TAG) derivative.
      The reduction of (3)H-MNA to pheromone proceeded through the coenzyme A
      intermediate. Mature females reduced significantly more precursor to pheromone
      than the immature females and the males, both in vivo and in vitro, indicating
      that the reduction of MNA to MNol is a regulated step involved in pheromone
      production. Using the in vitro assay reported herein, studies are ongoing in our
      lab to purify and characterize the enzyme catalyzing the reduction.

PMID- 16651188
TI  - Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae
      to dietary plant xenobiotics.
AB  - The response of mosquito larvae to plant toxins found in their breeding sites was
      investigated by using Aedes aegypti larvae and toxic arborescent leaf litter as
      experimental models. The relation between larval tolerance to toxic leaf litter
      and cytochrome P450 monooxygenases (P450s) was examined at the toxicological,
      biochemical and molecular levels. Larvae pre-exposed to toxic leaf litter show a
      higher tolerance to those xenobiotics together with a strong increase in P450
      activity levels. This enzymatic response is both time- and dose-dependent. The
      use of degenerate primers from various P450 genes (CYPs) allowed us to isolate 16
      new CYP genes belonging to CYP4, CYP6 and CYP9 families. Expression studies
      revealed a 2.3-fold over-expression of 1 CYP gene (CYP6AL1) after larval pre
      exposure to toxic leaf litter, this gene being expressed at a high level in late
      larval and pupal stages and in fat bodies and midgut. The CYP6AL1 protein has a
      high level of identity with other insect's CYPs involved in xenobiotic
      detoxification. The role of CYP genes in tolerance to natural xenobiotics and the
      importance of such adaptive responses in the capacity of mosquitoes to colonize
      new habitats and to develop insecticide resistance mechanisms are discussed.

PMID- 16651189
TI  - Highly conserved piggyBac elements in noctuid species of Lepidoptera.
AB  - The piggyBac transposable element was originally discovered in a Trichoplusia ni
      cell line and nearly identical elements were subsequently discovered in the
      tephritid fly, Bactrocera dorsalis. This suggested the existence of piggyBac in
      additional insects and this study shows highly conserved, though not identical,
      piggyBac sequences in the noctuid species Heliocoverpa armigera, H. zea, and
      Spodoptera frugiperda, as well as new piggyBac sequences from the T. ni
      organismal genome. Genomic piggyBac elements could not be unambiguously
      identified in several other moth species indicating a discontinuous presence of
      piggyBac in the Lepidoptera. Most sequences have greater than 95% nucleotide
      identity to the original IFP2 piggyBac, except for a more diverged sequence in S.
      frugiperda, having approximately 78% identity. Variants of 1.3 and 0.8kb
      sequences found in both H. armigera and H. zea most likely became established by
      interbreeding, supporting the notion that the species are conspecific. None of
      the independent piggyBac sequences isolated from T. ni larval genomes are
      identical to IFP2, though all have an uninterrupted reading frame with the
      potential for encoding a functional transposase. The piggyBac sequences from T.
      ni and the Helicoverpa species, as well as those previously reported from B.
      dorsalis, all share three common nucleotide substitutions resulting in a single
      amino acid substitution in the transposase. This suggests that the original IFP2
      piggyBac is a related variant of a predecessor element that became widespread.
      The existence of conserved piggyBac elements, some of which may have been
      transmitted horizontally between lepidopteran species, raises important
      considerations for the stability and practical use of piggyBac transformation
      vectors.

PMID- 16651190
TI  - A transgenic silkworm expressing the immune-inducible cecropin B-GFP reporter
      gene.
AB  - To analyze cecropin B promoter (P-CecB) activity in vivo, we constructed
      transgenic silkworms that expressed EGFP under the control of P-CecB using the
      piggyBac transposable element. Genomic Southern blot analysis of the G1 and G2
      generations indicated the stable insertion of EGFP in the genome. Injection of
      Escherichia coli cells into the larvae strongly induced EGFP expression in the
      fat bodies and all five hemocyte cell types. Northern blot analysis indicated
      that the expression kinetics of EGFP in the fat bodies following bacterial
      injection were correlated with that of endogenous CecB. Flow cytometric analysis
      of the hemocytes revealed that EGFP expression was increased by bacteria, but not
      by yeast. Our results indicate that the features of EGFP expression in the
      transgenic silkworm are equivalent to those of endogenous CecB and that P-CecB
      activation can be monitored by EGFP expression using transgenic silkworms.

PMID- 16651191
TI  - So you want to be a researcher...

PMID- 16651192
TI  - Perioperative complications of the Agility total ankle replacement in 50 initial,
      consecutive cases.
AB  - Although functional and clinical outcomes after total ankle arthroplasty have
      been promising, a steep learning curve has been recognized. In addition, the
      performance of concomitant hindfoot realignment procedures is controversial. The
      purpose of this study was to report on a single surgeon's experience with the
      first 50 total ankle arthroplasty procedures. We wanted to define the
      characteristics of the learning curve and whether the rate of complications was
      increased in patients who required complex reconstruction for preexistent foot
      and ankle deformities. This was a retrospective study of 50 cases with an average
      follow-up of 24.2 months. The patient population consisted of 18 men and 30 women
      with an average age of 57.6 years. Twenty-six percent of the cases had
      concomitant bony realignment procedures, while 20% had prior history of major
      hindfoot corrective procedures. There were 19 cases with intraoperative malleolar
      fractures, 12 cases that exhibited some degree of malalignment, and 6 cases of
      syndesmotic nonunion, and 8 ankles required early component revision. Minor wound
      complications that resolved with local wound care occurred in 9 cases, while 1
      patient had a major wound complication requiring flap coverage. Each of these
      complications, other than wound complications, decreased with the surgeon's
      experience. Our results also indicate that the performance of major realignment
      procedures at the same time of implant arthroplasty is not associated with an
      increased incidence of complications. The results of this study suggest that
      total ankle arthroplasty is associated with a learning curve. Perioperative
      complications may potentially decrease with surgeon experience.

PMID- 16651193
TI  - A critical analysis of Dudley Morton's concept of disordered foot function.
AB  - The name Morton is associated with a foot structure characterized by a short
      first metatarsal in comparison with the adjacent second metatarsal. Dudley Morton
      is credited with recognizing a short first metatarsal as being a primary defect
      of the foot. Morton, an anatomist, approached his observation from an
      evolutionary perspective. His theory of disordered foot function was based on the
      premise that human alignment centered on an "axis of leverage" and around an
      "axis of balance." Morton concluded that the presence of a short first metatarsal
      was compounded when the first metatarsal segment was hypermobile. Shortness and
      hypermobility diminished the capacity of the first metatarsal segment to carry
      weight, allowed pronation during activity, and led to an overload of the central
      metatarsals. The term Morton Foot sprang from his teachings. The extensive
      writings of Morton are commonly cited even today. This study compares Morton's
      teachings with research published during the last 70 years, which either supports
      or refutes his claims.

PMID- 16651194
TI  - Morbidity associated with high gastrocnemius recession: retrospective review of
      126 cases.
AB  - To evaluate morbidity associated with surgical lengthening of the gastrocnemius,
      medical records were reviewed retrospectively for 126 patients (mean age, 49.7
      years; range, 8-78 years) who had undergone open gastrocnemius recession. Ten
      patients had isolated recession; 116 had gastrocnemius recession with an
      additional foot or ankle procedure on the ipsilateral limb. During a mean follow
      up period of 19 months (range, 6-50 months), all patients were examined for any
      postoperative complications associated with the recession. Complications were
      defined as the presence of postoperative infection, wound dehiscence, nerve
      problems, decreased muscle strength, scar problems, or calcaneus gait
      (overlengthening). Uncomplicated outcome was defined as absence of all these
      complications and return to regular activity, both occurring during a follow-up
      of at least 6 months. Postsurgical complications developed in 9 (6%) of the 126
      patients: 6 (4%) had scar problems, 2 (1.33%) had wound dehiscence, 2 (1.33%) had
      infection, 3 (2%) had nerve problems, and 1 (0.67%) developed complex regional
      pain syndrome. No patient complained of either a limp or gait disturbance.
      Neither persistent decrease in muscle strength nor calcaneus gait was seen. These
      data suggest that the open gastrocnemius recession procedure has low associated
      morbidity.

PMID- 16651195
TI  - Radiographic measurements of patients with juvenile hallux valgus compared with
      age-matched controls: a cohort investigation.
AB  - The purpose of this study was to investigate radiographic measurements in a
      cohort of patients with juvenile hallux valgus (with a hallux valgus angle > 15
      degrees ) using standardized weightbearing x-rays compared with an age-matched
      control group. First metatarsal protrusion distance, metatarsus primus adductus
      angle, metatarsus adductus, first metatarsal cuneiform angle, calcaneal
      inclination angle, and talocalcaneal angles were assessed with discriminant
      functional analysis. A total of 37 sets of data were analyzed from patients with
      a mean age of 13.45 +/- 1.75 years. The study identified 2 significant components
      of juvenile hallux valgus: a positive first metatarsal protrusion distance (P
      <.001) and metatarsal primus adductus angle (P = .002). Discriminant functional
      analysis was then used to determine the best predictors of juvenile hallux
      valgus. This analysis allowed only 1 variable, metatarsal protrusion distance, as
      a predictor of whether juvenile hallux valgus was present (P < .001), with 94.3%
      accuracy. This study showed that a positive metatarsal protrusion distance is a
      significant component of juvenile hallux valgus.

PMID- 16651196
TI  - Comparison of initial compression force across the subtalar joint by two
      different screw fixation techniques.
AB  - The purpose of this study was to compare the magnitude of compressive force
      across the posterior facet of the subtalar joint between 2 different screw
      orientations in a simulated subtalar fusion model fixated with cannulated 7.3-mm
      screws. Eight paired fresh, frozen cadaver feet were used. Before testing, the
      bone mineral density of the calcanei and tali was measured with dual energy x-ray
      absorptiometry to ensure comparable bone mineral density. The paired cadaver
      calcanei and tali were noted to have less than .05 g/cm(2) difference in bone
      mineral density. The paired specimens were each randomly assigned to 1 of 2
      methods of fixation across the subtalar joint: a plantar approach, where the
      screw was oriented vertically from the plantar aspect of the calcaneus, distal to
      the tuberosity; and a posterior approach, where the screw was oriented obliquely
      from the posterior calcaneal tuberosity. A load-sensing washer was placed under
      the cancellous screw head before insertion of the screw to measure the magnitude
      of the compression force across the simulated fusion site. The mean compression
      force for the posterior-to-anterior approach was 581 N, with a standard deviation
      of 242 N. The mean force for the plantar-to-superior approach was 604 N, with a
      standard deviation of 276 N. The compression force obtained by the 2 approaches
      was not significantly different (P = .74). The plantar-to-superior fixation
      technique represents an alternative subtalar arthrodesis technique to the
      posterior-to-anterior approach, potentially allowing one to revise a previously
      failed arthrodesis when the standard fixation techniques cannot be applied.

PMID- 16651197
TI  - Superficial peroneal nerve (superficial fibularis nerve): the clinical
      implications of anatomic variability.
AB  - The purpose of this study is to refine further the knowledge about the anatomic
      variability of the superficial peroneal nerve in the middle third of the leg.
      Approaching the superficial peroneal nerve in this location is required: 1) when
      either the deep or the superficial peroneal nerve must be resected for the
      treatment of dorsal foot pain; 2) when a neurolysis of the superficial peroneal
      nerve is required; 3) when a fasciotomy must be performed either for trauma or
      for exertional compartment syndrome surgery; and 4) during elevation of a
      fasciocutaneous or fibular flaps. Because of the variability encountered during
      these procedures, a prospective study was carried out via lower extremity cadaver
      dissection with fresh, frozen specimens. A total of 35 nonpaired lower
      extremities and 40 paired lower extremities were dissected with 3.5 loupe
      magnification. The superficial peroneal nerve was identified in the lateral
      compartment immediately adjacent to the fascial septum in 72% of the specimens
      (54 of 75), with a branch in both the anterior and the lateral compartment in 5%
      of the specimens (4 of 75), and located in the anterior compartment in only 23%
      of the specimens (17 of 75). The clinical implications of these anatomic findings
      are that the surgeon operating in the anterior and lateral compartments of the
      leg should be aware that the superficial peroneal nerve may be located in the
      lateral compartment and may also exhibit branches in both the anterior and
      lateral compartments.

PMID- 16651198
TI  - Treatment of severe and neglected clubfoot with a double zigzag incision: outcome
      of 21 feet in 15 patients followed up between 1 and 5 years.
AB  - Patients presenting late for treatment of clubfoot deformity are still common in
      many parts of the world. These feet are often rigid and severely deformed.
      Surgical correction is the prevailing option to attain a plantigrade foot, and
      the extent of correction required predisposes to wound-healing problems. We
      present the results of treatment of 15 patients (21 feet) with severe, untreated
      congenital talipes equino varus, who underwent operations using a double zigzag
      incision as a single-stage procedure. These patients ranged in age from 6 months
      to 4 years and presented late, having received no treatment or inadequate
      treatment since birth. The desired end point of the study was a fully corrected
      foot with a wound that would heal primarily without complications. The etiology
      was isolated congenital talipes equino varus in 11 patients and arthrogryposis
      multiplex congenita in 4 patients. Eleven patients were boys and 4 were girls; 6
      patients underwent bilateral procedures. The patients were graded preoperatively
      and postoperatively using the Dimeglio classification, with 10 feet classified
      preoperatively as grade 3 and 11 graded as grade 4. Desired correction was
      achieved in all feet, and all wounds healed uneventfully with no complications.
      This single-stage technique is very safe and cost-effective and is an easy
      alternative to standard techniques for dealing with late-presenting untreated
      severe clubfoot deformities.

PMID- 16651199
TI  - Metastatic squamous cell carcinoma resembling cellulitis and osteomyelitis of the
      fifth toe.
AB  - Statistically, metastasis of carcinomas to pedal phalanges is rare. However, true
      to all bone metastases of the body, its presence is associated with a very poor
      prognosis. A case of metastatic sinonasal squamous cell carcinoma to the fifth
      toe is presented followed by a review of the literature.

PMID- 16651200
TI  - Extrusion of metal radiological marker from a total ankle replacement insert: a
      case report.
AB  - Total ankle arthroplasty has become an increasingly performed procedure for the
      treatment of ankle arthritis. Failures related to polyethylene inserts can result
      from uncorrected deformities or malalignment of the components. We report a case
      of a 63-year-old man who underwent total ankle arthroplasty for osteoarthritis of
      the ankle. The talar component was placed in neutral alignment. Initial
      postoperative recovery and rehabilitation were unremarkable. At 9 months
      postoperatively, plain radiographs of the ankle showed worsening varus tilt when
      compared with radiographs taken earlier. There was also radiographic evidence of
      separation of the posterior metal marker, suggestive of a fracture of the
      polyethylene insert. Revision surgery to correct the varus tilt and replace the
      polyethylene insert was performed. At operation, the polyethylene insert was
      found to be intact with no evidence of fracture. The posterior metal marker of
      the polyethylene insert was found to be extruded from the insert. Small degrees
      of ankle prosthesis malalignment can lead to various degrees of polyethylene
      liner failure, such as metal marker extrusion. This article also shows that these
      metal markers may not be accurate indicators of the integrity of the polyethylene
      insert.

PMID- 16651201
TI  - The transverse dorsal approach to displaced multi-metatarsal fractures.

PMID- 16651202
TI  - Rail external fixation for stabilization of closing base wedge osteotomies and
      Lapidus procedures: a retrospective analysis of sixteen cases.

PMID- 16651204
TI  - Sexual functioning and satisfaction in nonresponders to testosterone gel:
      Potential effectiveness of retreatment in hypogonadal males.
AB  - There is a slow but continuous decline in testosterone (T) levels with age, with
      a substantial percentage of males exhibiting T levels in the hypogonadal range.
      This age-dependent decline in circulating androgens is associated, in large part,
      with reduced sexual functioning and libido. The effectiveness of TestimR 1%
      (Auxilium Pharmaceuticals, Inc., Norristown, Pennsylvania) topical T gel was
      evaluated in older hypogonadal males who failed to experience satisfactory
      symptom relief after treatment with AndroGelR 1% (Solvay Pharmaceuticals, Inc.,
      Marietta, Georgia). In this open-label study, consecutive subjects were assigned
      randomly to experimental treatment with Testim 1% (5 g) or to maintenance therapy
      (control group) with AndroGel 1% (5 g). Seventy-six experimental subjects and 75
      control subjects were followed for 4 weeks to evaluate improvements in sexual
      functioning and satisfaction. Changes from baseline in the 5 domains of the Brief
      Male Sexual Function Inventory were compared between groups. The mean percentage
      improvement favored the experimental treatment in sexual drive (23% vs 16%, P <
      0.3), erectile function (32% vs 8%, P < 0.03), ejaculatory function (11% vs 9%, P
      < 0.4), problem assessment (47% vs 12%, P < 0.01), and sexual satisfaction (62%
      vs 23%, P < 0.02). A greater percentage of subjects also reported satisfaction
      with the experimental treatment (55% vs 33%, P < 0.02), and these subjects were
      less likely to require upward dose titration at the final follow-up visit (53% vs
      72%, P < 0.03). Consideration of Testim 1% gel in patients who have an inadequate
      response to prior T therapy is encouraged, although it is difficult to estimate
      the contribution of nonspecific study effects (eg, placebo) in this trial.

PMID- 16651205
TI  - Improvement in sexual functioning and satisfaction in nonresponders to
      testosterone gel: clinical effectiveness in hypogonadal, HIV-positive males.
AB  - Impairment in gonadal function with reduced testosterone (T) levels is commonly
      associated with HIV infection and patients often complain of diminished libido
      and sexual dysfunction. The effectiveness of Testim 1% (Auxilium Pharmaceuticals,
      Inc., Norristown, Pennsylvania) topical T gel was evaluated in HIV-positive males
      who failed to experience satisfactory symptom relief following prior treatment
      with AndroGel 1% (Solvay Pharmaceuticals, Inc., Marietta, Georgia). In this open
      label study, consecutive subjects were randomly assigned to experimental
      treatment with Testim 1% (5 g) or to maintenance therapy (control group) with
      AndroGel 1% (5 g). Twenty-four experimental subjects and 24 control subjects were
      followed for 4 weeks to evaluate improvements in sexual functioning and
      satisfaction. Changes from baseline in the 5 domains of the Brief Male Sexual
      Function Inventory (BMSFI) were compared between groups. The average percentage
      improvement favored the experimental treatment in all 5 comparisons of the BMSFI,
      including sexual drive (53% vs 18%, P < 0.001), erectile function (49% vs 7%, P <
      0.004), ejaculatory function (15% vs 8%, P < 0.14), problem assessment (59% vs
      12%, P < 0.003), and sexual satisfaction (58% vs 9%, P < 0.006). A greater
      percentage of subjects also reported satisfaction with the experimental treatment
      (85% vs 48%, P < 0.03), and these subjects were less likely to require upward
      dose titration at the final follow-up visit (30% vs 74%, P = 0.01). It is
      hypothesized that the results of the current study may be explained, in part, by
      an improved pharmacokinetic profile of the experimental intervention.
      Consideration of Testim 1% gel in HIV patients who have an inadequate response to
      prior T therapy is encouraged, although it is difficult to estimate the
      contribution of nonspecific study effects (eg, placebo) in this trial.

PMID- 16651206
TI  - Testosterone therapy in hypogonadal men. Introduction.

PMID- 16651207
TI  - Benefits of a new testosterone gel formulation for hypogonadal men.
AB  - Hypogonadism is a common problem in men. It affects 2% to 30% of men aged 40 to
      59 years, 20% to 45% aged 60 to 69 years, 34% to 70% aged 70 to 79 years, and
      most men aged >80 years. Hypogonadism is also highly prevalent in men with
      chronic illnesses, such as HIV infection. The low testosterone (T) levels
      associated with hypogonadism impair sexual function and many other aspects of
      health and well-being. In aging men and in those who are chronically ill,
      impaired gonadal function is characterized by subtle changes at many stages of T
      regulation. T therapy reverses the effects of hypogonadism, improving sexual
      function, body composition, mood, and well-being. Although many forms of T
      therapy are available, some therapies have limitations that render them
      ineffective or inconvenient. A new type of T gel has improved pharmacokinetic and
      clinical profiles compared with other forms of T therapy. This T gel has been
      shown to be effective in older men and in men with HIV infection, despite
      unsatisfactory response to earlier T-gel therapy.

PMID- 16651209
TI  - Eye safety--you can make the difference.

PMID- 16651210
TI  - Color vision screening for individuals with intellectual disabilities: a
      comparison between the Neitz Test of Color Vision and Color Vision Testing Made
      Easy.
AB  - BACKGROUND: The Neitz Test of Color Vision (Neitz) and Color Vision Testing Made
      Easy(trade mark) (CVTME) were compared to determine which test was more effective
      in evaluating patients with intellectual disability (i.e., mental retardation)
      and developmental delay. METHODS: Two hundred eight Special Olympics floor hockey
      athletes were screened in San Diego, California, and 93 athletes were screened in
      Long Beach, California for a total of 301 athletes. Each athlete was administered
      the CVTME and the Neitz tests. RESULTS: The pass rate for the CVTME was 94.6% (n
      = 93) at Long Beach and 96.2% (n = 208) at San Diego. Every athlete was able to
      complete the CVTME. The pass rate for the Neitz was 38.7% at Long Beach and 56.7%
      at San Diego. Additionally, 10.8% of the Long Beach athletes and 12.5% of the San
      Diego athletes were unable to understand the Neitz. In addition, there was a low
      level of agreement between the results from the 2 tests with kappa = 0.081 for
      the San Diego data and 0.028 for the Long Beach data. CONCLUSIONS: This study
      suggests that the CVTME continues to be the screening test of choice in
      evaluating color vision in individuals with intellectual disability. The Neitz
      had more failing scores on the first attempt and more total failing scores
      leading to over-referrals, making it an inappropriate screening test for
      individuals with intellectual disability and developmental delay.

PMID- 16651211
TI  - Crouzon syndrome.
AB  - BACKGROUND: Crouzon syndrome is a rare genetic disorder characterized by
      distinctive malformations of the skull and facial region. Premature cranial
      suture closure is the most common skull abnormality. Optic disc edema and
      proptosis are among the most common ocular findings. CASE REPORT: We present a
      case of a 5-year-old girl with Crouzon syndrome displaying classic facial
      abnormalities along with proptosis and papilledema. The child's condition was
      improved dramatically after a monoblock advancement procedure. CONCLUSIONS: The
      differential diagnosis of the condition and treatment options are discussed. The
      referring optometrist can play an integral role in the multidisciplinary care the
      patients require.

PMID- 16651212
TI  - Primary acquired melanosis of the conjunctiva.
AB  - BACKGROUND: Primary acquired melanosis (PAM) presents as a unilateral patchy area
      of conjunctival pigmentation mostly found in middle-aged or elderly white
      patients. Because PAM has the potential of becoming malignant, it is important to
      recognize PAM and to rule out other causes of pigmented lesions. The presence or
      absence of atypia is helpful in determining the potential for malignancy, because
      PAM without atypia is usually benign, whereas PAM with atypia may convert into a
      conjunctival melanoma. If atypia is present, the presence or absence of
      epithelioid cells and the pattern of intraepithelial growth are the main factors
      in determining the likelihood of neoplastic transformation. However, atypia can
      only be determined with histopathologic examination. Therefore, a biopsy is
      usually recommended. CASE REPORT: A 72-year-old white man presented for his
      annual examination with no visual complaints. His ocular history was remarkable
      for early cataracts and for a choroidal nevus. Slit lamp examination found a
      large dark area of elevated conjunctival pigmentation at the medial canthus that
      extended onto the superior bulbar conjunctiva and superior palpebral conjunctiva
      in the left eye. No conjunctival pigmentation had been noted previously. Results
      of a biopsy indicated primary acquired melanosis with atypia. The lesion was
      surgically excised, and the conjunctiva was reconstructed with an amniotic
      membrane graft. The patient was subsequently treated with topical 5-fluorouracil
      chemotherapy. There have been no signs of recurrence to date after his treatment.
      CONCLUSION: Because of the potential for malignancy, biopsies of all cases of
      primary acquired melanosis are indicated. If atypia is present, treatment options
      include local excision, cryotherapy, and topical chemotherapy.

PMID- 16651213
TI  - Effect of heterophoria measurement technique on the clinical accommodative
      convergence to accommodation ratio.
AB  - BACKGROUND: Measurement of the stimulus accommodative convergence to
      accommodation (AC/A) ratio is a standard procedure in clinical optometric
      practice. Typically, heterophoria is assessed at several accommodative stimulus
      levels, and the gradient of the vergence to accommodation function computed. A
      number of procedures are available for the subjective measurement of
      heterophoria, but it is unclear whether the use of different vergence measurement
      techniques will alter the obtained AC/A value. Accordingly, the current study
      compared AC/A ratios measured using 3 clinical subjective heterophoria tests,
      namely the von Graefe (VG), Maddox Rod (MR), and Modified Thorington (MT)
      procedures. METHODS: The AC/A ratio was measured in 60 visually normal subjects
      between 20 and 25 years of age using each of the 3 procedures listed above. The
      accommodative stimulus was varied by the introduction of +/-1.00 diopter (D)
      spherical lenses over the distance refractive correction while subjects viewed a
      target at a viewing distance of 40 cm. To examine the repeatability of each
      procedure, the AC/A ratio was measured on 2 separate occasions for each
      measurement technique, with the 2 sessions being separated by at least 24 hours.
      RESULTS: Mean values of stimulus AC/A ratio measured using the VG, MR, and MT
      procedures were 3.47, 2.99, and 2.46Delta/D, respectively. These differences were
      significant (p=0.0001). In addition, the coefficient of repeatability for the 3
      techniques was 2.22, 1.99, and 1.20 Delta/D, respectively. CONCLUSIONS: Ratios
      obtained using the Modified Thorington technique with +/-1.00 D lenses showed the
      best repeatability, whereas the poorest repeatability was found with the von
      Graefe technique when only +1.00 D lenses were used to vary the accommodative
      stimulus. Accordingly, we recommend that that Modified Thorington procedure with
      +/-1.00 D lenses be used to quantify heterophoria during clinical measurement of
      the stimulus AC/A ratio.

PMID- 16651214
TI  - Investigation of axial symptoms after cervical laminoplasty, using questionnaire
      survey.
AB  - BACKGROUND CONTEXT: Cervical laminoplasty is a good strategy for cervical
      myelopathy, but some postoperative patients complain of obstinate axial symptoms
      after surgery, that is, nuchal pain, neck stiffness, and shoulder pain. It was
      reported that these symptoms proved to be more serious than has been believed and
      should be considered in the evaluation of the outcome of cervical spinal surgery.
      However, axial symptoms are sometimes recognized before surgery, or also after
      corpectomy. Addressing this issue becomes complicated. PURPOSE: We investigate
      the difference in axial symptoms before and after laminoplasty and discuss the
      characteristics of these symptoms as a surgical complication. STUDY
      DESIGN/SETTING: We conducted a questionnaire survey and reviewed the medical
      records of respondents. PATIENT SAMPLE: All of the 180 patients who underwent a
      spinous process-splitting laminoplasty for cervical myelopathy caused by
      degenerative disease in our institution from 1993 until 2002 and were followed
      for 2 years or longer after surgery. OUTCOME MEASURES: Self-report measures and
      functional measures. The questionnaire elicited information as follows: the
      location and characteristics of pre- and postoperative symptoms, frequency and
      duration of postoperative symptoms, and impairment in activities of everyday
      living, analgesic use, and the duration of use of cervical orthosis after
      surgery. METHODS: We divided axial symptoms into four characteristics based on
      previous reports: "pain," "heaviness," "stiffness," and "other." An illustration
      of the upper back on which respondents could mark each characteristic was
      utilized to acquire information about the location of axial symptoms. The
      following information was gathered from medical records and statistically
      analyzed: whether postoperative axial symptoms were related or not, age, sex,
      neurological findings, the period of cervical orthosis, surgery time, blood loss,
      with or without reconstruction surgery of the semispinalis cervicis muscle, and
      preoperative axial symptoms. RESULTS: For all of the 51 respondents, the average
      time since surgery was 4.1 years at the time of investigation; 42 patients
      complained of postoperative axial symptoms; 26 patients stated the duration of
      symptoms after surgery to be "more than 2 years." The surgical outcome of this
      group, however, did not differ from that of the 2-year-or-less group. Axial
      symptoms, which accounted for 13.3% of all answers about postoperative impairment
      of everyday living, were similar to hand numbness. Of respondents with
      postoperative axial symptoms, 52.2% stated the frequency of affliction to be "all
      day long," but 34.8% replied "rarely" to frequency of use of analgesics. Axial
      symptoms in the nuchal region increased from 45.2% to 48.6% after surgery.
      "Stiffness" was the most common characteristic before and after surgery, but
      "pain" significantly increased from 24.6% before surgery to 38.4% after surgery.
      We speculate that the principal manifestation of axial symptoms might be pain and
      that the nuchal region might be the predominant region for axial symptoms. There
      was no significant difference in age, blood loss, operative time, sex, duration
      of use of cervical orthosis, reconstructive surgery, and preoperative symptoms
      between two groups--those who complained of axial symptoms after surgery, and
      those who did not. CONCLUSIONS: In this survey, axial symptoms were not usually
      so severe as to require analgesic use and did not worsen the Japanese Orthopaedic
      Association score after surgery; symptoms were, however, considered to
      continuously affect everyday life as much as hand numbness. Regarding their
      features, we speculate the main characteristics of axial symptoms might be pain
      and that the nuchal region might be the predominant region for axial symptoms.
      Our data are consistent with the hypothesis that laminoplasty is not, as such, an
      effective treatment for axial neck pain and that axial symptoms may in fact be
      worsened by the procedure.

PMID- 16651215
TI  - Enlarging retro-odontoid pseudotumor after expanding cervical laminoplasty in the
      presence of kyphosis.
AB  - BACKGROUND CONTEXT: In cranio-vertebral junction, retro-odontoid pseudotumor
      without evidence of rheumatoid arthritis is a rare condition. PURPOSE: To discuss
      the mechanism of enlarging retro-odontoid pseudotumor after expanding cervical
      laminoplasty as a predictable complication. STUDY DESIGN: We report a rare case
      of an elderly man with non-inflammatory retro-odontoid pseudotumor after cervical
      expanding laminoplasty. PATIENT SAMPLE: A 76-year-old man presented with
      progressive quadriparesis of two week's duration caused by enlarging retro
      odontoid soft tissue mass after cervical laminoplasty. OUTCOME MEASURES: Pre- and
      postoperative image, including X-ray and MRI, and the Japanese Orthopaedic
      Association scores for cervical myelopathy were assessed. METHODS: The patient
      subsequently underwent resection of the posterior arch of the atlas and posterior
      fusion from the occiput to C6 using Olerud system without removal of the retro
      odontoid soft tissue mass. RESULTS: One year after surgery, the Japanese
      Orthopaedic Association scores for cervical myelopathy improved from 1 to 10
      points, and postoperative MRI showed a mild reduction in the size of the retro
      odontoid soft tissue mass. CONCLUSIONS: The kyphotic stability from C3 to C7
      after laminoplasty, leading to a compensatory hyperlordosis at the
      occipitocervical junction, may cause the development of a degenerative
      osteoarthritic change, resulting in the production of an enlarging mass. Not only
      posterior compression of spinal cord due to posterior arch of the hyperextended
      atlas but also anterior compression of spinal cord due to retro-odontoid
      pseudotumor probably triggered the severe myelopathy. Laminoplasty may be
      inappropriate in cervical myelopathy with kyphosis.

PMID- 16651216
TI  - Design limitations of Bryan disc arthroplasty.
AB  - BACKGROUND CONTEXT: Disc arthroplasty is gaining momentum as a surgical procedure
      in the treatment of spinal degenerative disease. Results must be carefully
      scrutinized to recognize benefits as well as limitations. PURPOSE: The aim of
      this study was to investigate factors associated with segmental kyphosis after
      Bryan disc replacement. STUDY DESIGN/SETTING: Prospective study of a
      consecutively enrolled cohort of 10 patients treated in a single center using the
      Bryan cervical disc prosthesis for single-level segmental reconstruction in the
      surgical treatment of cervical radiculopathy and/or myelopathy. Radiographic and
      quality of life outcome measures. METHODS: Static and dynamic lateral radiographs
      were digitally analyzed in patients undergoing Bryan disc arthroplasty throughout
      a minimum 3-month follow-up period. Observations were compared with preoperative
      studies looking for predictive factors of postoperative spinal alignment.
      RESULTS: Postoperative end plate angles through the Bryan disc in the neutral
      position were kyphotic in 9 of 10 patients. Compared with preoperative end plate
      angulation there was a mean change of -7 degrees (towards kyphosis) in
      postoperative end plate alignment (p=.007, 95% confidence interval [CI] -6
      degrees to -13 degrees). This correlated significantly with postoperative
      reduction in posterior vertebral body height of the caudal segment (p=.011,
      r2=.575) and postoperative functional spine unit (FSU) kyphosis (p=.032, r2=.46).
      Despite intraoperative distraction, postoperative FSU height was significantly
      reduced, on average by 1.7 mm (p=.040, 95% CI 0.5-2.8 mm). CONCLUSIONS:
      Asymmetrical end plate preparation occurs because of suboptimal coordinates to
      which the milling jig is referenced. Although segmental motion is preserved,
      Bryan disc arthroplasty demonstrates a propensity towards kyphotic orientation
      through the prosthesis likely as a result of intraoperative lordotic distraction.
      FSU angulation tends towards kyphosis and FSU height is decreased in the
      postoperative state from lack of anterior column support. Limitations of Bryan
      cervical disc arthroplasty should be carefully considered when reconstruction or
      maintenance of cervical lordosis is desirable.

PMID- 16651217
TI  - Range of motion and adjacent level degeneration after lumbar total disc
      replacement.
AB  - BACKGROUND CONTEXT: There are no published studies on the relationship between
      total disc replacement (TDR) motion and the development of adjacent level
      degeneration (ALD). Because prevention of ALD is the underlying justification for
      TDR, studies investigating the validity of this concept are essential. PURPOSE:
      To examine the relationship between range of motion (ROM) and ALD 8.7 years after
      lumbar TDR. STUDY DESIGN/SETTING: Retrospective radiographic and chart review.
      PATIENT SAMPLE: Forty-two patients 8.7 years after lumbar TDR. OUTCOME MEASURES:
      Radiographic flexion-extension and ALD. Modified Stauffer-Coventry score.
      Oswestry Disability Questionnaire. Subjective patient ratings of back pain, leg
      pain, and disability. METHODS: We reviewed the flexion-extension radiographs of
      42 patients 8.7 years after TDR. Cephalad adjacent levels were evaluated for
      degeneration: loss of disc space height, anterior osteophyte formation, or
      dynamic flexion-extension instability. Graphical analysis of motion and the
      prevalence of ALD was performed. A statistical relationship between ALD and
      clinical outcome was sought. RESULTS: Ten of 42 patients evaluated (24%) had
      radiographic ALD. The mean motion was 3.8 degrees +/-2.0 degrees. The patients
      with ALD had mean motion of 1.6 degrees +/-1.3 degrees whereas the patients
      without ALD had motion of 4.7 degrees +/-4.5 degrees (p=.035). A clear
      relationship between motion and the presence of ALD at 8.7-year follow-up was
      observed. Patients with motion 5 degrees or greater (n=13) had a 0% prevalence of
      ALD. Patients with motion less than 5 degrees (n=29) had a 34% prevalence of ALD
      (p=.021, odds ratio 13.5). ALD had no statistically significant effect on
      clinical outcome although the sample size was small. CONCLUSIONS: At 8.7-year
      follow-up, the prevalence of ALD after TDR is higher in patients with motion less
      than 5 degrees. The presence of ALD had no significant effect on clinical
      outcome, but the sample size was small. These data suggest that patients with
      significant ROM after lumbar TDR may have reduced risk for radiographic ALD.

PMID- 16651218
TI  - The multidirectional bending properties of the human lumbar intervertebral disc.
AB  - BACKGROUND CONTEXT: While the biomechanical properties of the isolated
      intervertebral disc have been well studied in the three principal anatomic
      directions of flexion/extension, axial rotation, and lateral bending, there is
      little data on the properties in the more functional directions that are
      combinations of these principal anatomic directions. PURPOSE: To determine the
      bending flexibility, range of motion (ROM), and neutral zone (NZ) of the human
      lumbar disc in multiple directions and to determine if the values about the
      combined moment axes can be predicted from the values about principal moment
      axes. STUDY DESIGN/SETTING: Three-dimensional biomechanical analysis of the
      elastic bending properties of human lumbar discs about principal and combined
      moment axes. METHODS: Pure, unconstrained moments were applied about multiple
      axes. The bending properties (flexibility, ROM, and NZ) of isolated lumbar discs
      (n=4 for L2/L3 and n=3 for L4/L5) were determined in the six principal directions
      and in 20 combined directions. The experimental values were compared with those
      predicted from the linear combination of the six principal moment axes. RESULTS:
      The maximum and minimum values of the biomechanical properties were found at the
      principal moment axes. Among combined moment axes, ROM and NZ (but not
      flexibility) values were predicted from the principal moment axis values.
      CONCLUSIONS: The principal moment axes coincide with the primary mechanical axes
      of the intervertebral disc and demonstrate significant differences in direction
      for values of flexibility, ROM, and NZ. Not all combined moment axis values can
      be predicted from principal moment axis values.

PMID- 16651219
TI  - Disc arthroplasty design influences intervertebral kinematics and facet forces.
AB  - BACKGROUND CONTEXT: Total disc replacement is a novel approach for dynamically
      stabilizing a painful intervertebral segment. While this approach is gaining
      popularity, and several types of implants are used, the effect of disc
      arthroplasty on lumbar biomechanics has not been widely reported. Consequently,
      beneficial or adverse effects of this procedure may not be fully realized, and
      data for kinematic optimization are unavailable. PURPOSE: To characterize
      kinematic and load transfer modifications at L5/S1 secondary to joint
      replacement. STUDY DESIGN: A human cadaveric biomechanical study in which the
      facet forces and instant axes of rotation (IAR) were measured for different
      spinal positions under simulated weightbearing conditions before and after total
      disc replacement at L5/S1 using semiconstrained (3 degrees of freedom [DOF];
      Prodisc) and unconstrained (5 DOF; Charite) articulated implants. METHODS: Twelve
      radiographically normal human cadaveric L5/S1 joints (age range 45-64 years) were
      tested before and after disc replacement using Prodisc II implants (Spine
      Solutions, Paoli, PA) in six specimens and SB Charite III (Johnson & Johnson, New
      Brunswick, NJ) in six other specimens. Semiconstrained fixtures in combination
      with a servo-hydraulic materials testing system subjected the test specimens to a
      physiologic combination of compression and anterior shear. Multiple
      intervertebral positions were studied and included up to 6 degrees of flexion,
      extension, and lateral bending. The IAR was calculated for every 3-degree
      intervals, and the force through the facet joints was simultaneously measured
      using flexible intra-articular sensors. Data were analyzed using repeated
      measures analysis of variance. RESULTS: During flexion/extension, the average IAR
      positions and directions were not significantly modified by implantation with the
      exception that the IAR was higher relative to S1 end plate with the Charite
      (p=.028). The IAR had a vertically oriented centrode throughout flexion/extension
      with the Prodisc (p<.001) and the Charite (p<.016). The centrode tended to be
      greater with the Prodisc. There was a trend that the facet force was decreased
      throughout flexion/extension for the Prodisc; however, this was statistically
      significant only at 6 degrees extension (27%, p=.013). In lateral bending, the
      IAR was significantly modified by Prodisc replacement, with a decreased
      inclination relative to S1 end plate, (ie, increased coupled axial rotation).
      While the IAR moved in the horizontal plane toward the side of bending, this
      effect was more pronounced with the Prodisc. The ipsilateral facet force was
      significantly increased in 6 degrees lateral bending with the Charite (85%;
      p=.001). CONCLUSIONS: The degree of constraint affects post-implantation
      kinematics and load transfer. With the Prodisc (3 DOF), the facets were partially
      unloaded, though the IAR did not match the fixed geometrical center of the
      UHMWPE. The latter observation suggests joint surface incongruence is developed
      during movement. With the Charite (5 DOF), the IAR was less variable, yet the
      facet forces tended to increase, particularly during lateral bending. These
      results highlight the important role the facets play in guiding movement, and
      that implant constraint influences facet/implant synergy. The long-term
      consequences of the differing kinematics on clinically important outcomes such as
      wear and facet arthritis have yet to be determined.

PMID- 16651220
TI  - Measurement and analyses of the effects of adjacent end plate curvatures on
      vertebral stresses.
AB  - BACKGROUND: Vertebral end plates of the lumbosacral spine have various degrees of
      concavity and convexity. It is believed that the shape of the end plates alters
      the distribution of loads transferred along the spine, between the vertebrae.
      Animal models have been regularly used in the design and development of vertebral
      disc implants and cages; to date, very little information is known about the
      animal vertebral end plate curvature. PURPOSE: The purpose was to measure and
      analyze the end plate curvature in the cadaver human male-female, chimpanzee, and
      canine lumbar vertebral bones. STUDY DESIGN/SETTING: Nondestructive and
      nontouching scanning method was designed to obtain curvature in anterior
      posterior and medial-lateral directions in the cadaver bones. Statistical
      analysis was performed on the data collected, and this data was then used to
      create a biomechanical model to evaluate the load transmission. METHOD:
      Measurements in anterior-posterior and medial-lateral directions were performed
      on human, canine, and chimpanzee cadaver lumbar bones to obtain accurate data for
      the end plate curvatures. Six sets of measurements (on human male-female L4 lower
      to S1 upper end plates) were performed. A parametric vertebral motion segment
      model (with and without posterior elements) that includes the experimental
      curvature information was developed. The characteristic kidney-shaped cross
      sectional model was created using a parametric equation. This model was used to
      perform finite element analyses investigating the effects of the location of
      maximum curvature on the stress distributions. RESULTS: The measurements for
      different species showed that the canine and chimpanzees, the quadrupeds, have
      entirely different curvature of their upper end plates compared with those in
      humans, the bipeds. Also, the curvatures of the human S1 upper end plates are
      significantly different from the rest of the vertebrae. This is a very useful
      piece of information in the comparison of these species. The stress distribution
      varied as the location of the maximum curvature shifted from the center to a more
      posterior position. The stresses in the vertebral core were found to decrease,
      with the shell taking more loads. CONCLUSIONS: This provides essential
      information for rehabilitation and surgical techniques, including designs for
      various interbody devices such as fusion cages, bone grafts, and disc prosthesis.

PMID- 16651221
TI  - Cervical juxtafacet cysts: case report and literature review.
AB  - BACKGROUND: Juxtafacet cysts of the cervical and thoracic spine are rare and
      often present with myelopathy. Juxtafacet cysts are well recognized entities
      found commonly in the lumbar spine but are unusual in the cervical and thoracic
      spine. We present a case of a patient with gait disturbance and early myelopathy
      who was found to have a juxtafacet cyst at the cervico-thoracic junction. We
      further review the literature. PURPOSE: To describe a case of a cervico-thoracic
      juxtafacet cyst and review the literature. STUDY DESIGN: Case report and subject
      review. METHODS: One patient presenting with early myelopathy and pain underwent
      surgery for resection of the lesion. Pathologic analysis revealed a juxtafacet
      cyst. RESULTS: The patient recovered uneventfully with relief of his pain. Pubmed
      review revealed less than 30 similar cases in the literature. CONCLUSION:
      Juxtafacet cysts of the cervical spine are rare entities. These lesions comprise
      both synovial cysts and ganglion cysts. The benign lesions present with
      myelopathy and should be considered in patients with cystic lesions in the
      cervical spinal canal.

PMID- 16651222
TI  - Knowledge transfer in family physicians managing patients with acute low back
      pain: a prospective randomized control trial.
AB  - BACKGROUND CONTEXT: The process through which new scientific developments are
      incorporated into clinical practice is referred to as "knowledge transfer" and is
      currently the subject of great interest in many areas of clinical medicine.
      Family physicians managing patients with acute low back pain have been shown to
      have a poor overall rate of concordance with clinical practice guideline
      recommended treatments. New methods need to be developed to help physicians
      bridge the guideline implementation gap. PURPOSE: To determine the efficacy of a
      knowledge transfer method that communicates clinical practice guidelines to
      family physicians and their patients using patient-specific, physician-to
      physician communications. STUDY DESIGN: A prospective randomized controlled
      study. PATIENT SAMPLE: 428 patients with acute mechanical low back pain and
      accepted Workers' Compensation Board claims were studied. OUTCOME MEASURES:
      Concordance with specific clinical practice guideline-derived history taking
      items, physical examination procedures and treatment recommendations was
      determined. METHODS: Patients with acute mechanical back pain of less than 4
      weeks duration and accepted Workers' Compensation Board claims were randomly
      assigned to one of three groups. In Group 1 (control group) neither the patients
      nor their family physicians received any information concerning the guidelines.
      In Group 2, family physicians alone or as well as their patients (Group 3)
      received a summary of clinical practice guidelines at approximately 2 weeks
      postinjury. In addition, both Groups 2 and 3 received reminders summarizing the
      recommended guidelines for patients at three specific stages of their clinical
      course. All guideline correspondence was addressed to a specific family physician
      or patient, signed by the study physician-investigators, and specified the
      patient by name. RESULTS: Family physicians in the control and intervention
      groups demonstrated a high degree of concordance with the guideline-recommended
      history taking and physical examination procedures, but were generally highly
      discordant with guideline-recommended treatments. Significant improvement in
      guideline-concordant treatments was seen only with diminished recommendations of
      prolonged bed rest and passive therapies and an increase in recommended aerobic
      exercise. Concordance with guideline recommendations relating to the use of
      spinal manipulative therapy was poor in all study groups. CONCLUSIONS: A
      knowledge transfer method that involved patient-specific, physician-to-physician
      communication to family physicians or their patients at three stages of the
      patient's clinical course was largely unsuccessful in improving concordance with
      guideline treatment recommendations.

PMID- 16651223
TI  - Does the evidence for spinal manipulation translate into better outcomes in
      routine clinical care for patients with occupational low back pain? A case
      control study.
AB  - BACKGROUND CONTEXT: Previous research has identified clinical characteristics of
      patients who are likely to respond favorably to thrust manipulation. The
      application of this evidence and its effect on clinical outcomes among patients
      with occupational low back pain has not been examined. PURPOSE: Examine patients
      treated in physical therapy with occupational low back pain who fit a subgroup
      likely to respond to thrust manipulation. STUDY DESIGN/SETTING: Retrospective
      review of clinical database. PATIENT SAMPLE: Patients with low back pain of less
      than 16 days duration with no symptoms distal to the knee or signs of nerve root
      compression receiving workers' compensation and referred to physical therapy were
      included. OUTCOME MEASURES: Self-report measures: numeric pain rating and
      Oswestry disability questionnaire. FUNCTIONAL MEASURES: Number of visits,
      duration, and costs of physical therapy. METHODS: Physical therapy notes for the
      first two sessions were examined. Patients were categorized as having received
      thrust manipulation, nonthrust manipulation, or no manipulation. Pain intensity
      and disability were recorded at initial and final sessions. The number of
      sessions, length of stay, and costs of physical therapy were recorded.
      Comparisons were made between patients receiving manipulation versus no
      manipulation, and between those receiving thrust versus nonthrust manipulation.
      RESULTS: Two hundred fifteen patients were included (mean age 35.9 [+/-10.1]
      years, 67.9% male). Thrust manipulation was received by 107 (49.8%) patients; 36
      (16.7%) received nonthrust manipulation and 72 (33.5%) received no manipulation.
      Patients receiving manipulation (thrust or nonthrust) experienced greater
      reductions in pain and disability with treatment. Patients receiving thrust
      manipulation had fewer sessions, a shorter length of stay, and lower costs in
      physical therapy than patients receiving nonthrust manipulation. CONCLUSIONS: The
      evidence supporting superior clinical outcomes with the use of manipulation for a
      subgroup of patients was corroborated by this retrospective review of patients
      with occupational low back pain. The use of thrust manipulation appeared to be
      more efficient than the use of nonthrust manipulation for these patients.

PMID- 16651224
TI  - Changes in spine loading patterns throughout the workday as a function of
      experience, lift frequency, and personality.
AB  - BACKGROUND CONTEXT: Psychosocial stressors have been associated with low back
      pain reporting. However, response to psychosocial risk factors may be dependent
      on the individual's personality type that, in turn, can affect muscle recruitment
      and spine loading. This study explores how personality might be associated with
      spine loading during repetitive lifting performed throughout an entire work
      shift. PURPOSE: Assess spine loading as a function of an individual's personality
      type during repetitive, long-term exposure to a materials handling tasks. STUDY
      DESIGN: Laboratory experiment where experienced and inexperienced participants
      performed repetitive, asymmetric lifts at various load and lift frequency levels
      throughout a series of 8-hour exposure periods. Spine loads were monitored
      throughout the work period. PATIENT SAMPLE: Twelve novice and 12 experienced
      materials handlers who were asymptomatic for back pain. OUTCOME MEASURES: Spine
      compression, anterior-posterior (A/P) shear, and lateral shear at the L5-S1
      level. METHODS: Participants were categorized into personality types based upon
      the Myers-Briggs personality type indicator. An electromyography-assisted
      biomechanical model was used to assess spine compression, A/P shear, and lateral
      shear throughout the exposure period. RESULTS: The results indicate that
      intuitors had higher shear spinal loading regardless of moment exposure, lift
      frequency, and time through the work period, compared with the sensor personality
      type. In addition, higher spine compressive and shear forces occurred in the
      perceiver personality compared with the judgers' personality trait, regardless of
      moment and, often, lift frequency. Novice lifters typically experienced greater
      spine loading. CONCLUSIONS: The results suggest that when there exists a
      personality-job environment mismatch, spinal loading increases via an increase in
      antagonistic co-contraction. The trends suggest that inherent personality
      characteristics may play a role in one's motor control strategies when performing
      a repetitive lifting task.

PMID- 16651225
TI  - Low back pain incident episodes: a community-based study.
AB  - BACKGROUND CONTEXT: The available evidence regarding low back pain (LBP) incident
      episodes is not consistent. Such knowledge can add information for the potential
      contribution of preventive programs. PURPOSE: a) To evaluate annual incident
      episodes of LBP among the general population. b) To evaluate the contribution of
      demographic, lifestyle, and back pain history to LBP incident episodes. STUDY
      DESIGN: A community-based longitudinal study. PATIENT SAMPLE: A randomized sample
      of individuals, free of LBP at a previous cross-sectional survey. OUTCOME
      MEASURES: Low back pain during the past year. METHODS: Subjects were followed up
      after 1 year. Baseline data included back pain history, perception of general
      health, physical activity, smoking, work satisfaction, and demographic
      characteristics. RESULTS: Annual incident episodes of LBP were 18.4%. Those who
      experienced LBP during the past year had a lower baseline perception of general
      health and were less involved in sporting activities than those free of pain.
      Those without history of LBP were more likely to be free of back pain after 1
      year. CONCLUSIONS: The annual incident episodes of LBP are relatively high and
      relate indirectly to baseline perception of general health and to level of
      sporting activities. Those without history of LBP are more likely to be free of
      back pain after 1 year. These results raise the potential of LBP preventive
      programs for adult populations.

PMID- 16651226
TI  - Serum C-reactive protein levels correlate with clinical response in patients
      treated with antibiotics for wound infections after spinal surgery.
AB  - BACKGROUND CONTEXT: C-reactive protein (CRP) and erythrocyte sedimentation rate
      (ESR) have been used to diagnose postoperative infections after spinal surgery.
      However, it has not been demonstrated if resolution of the signs and symptoms of
      postoperative spinal wound infections in patients who are being treated with
      intravenous antibiotics correlates with these markers. PURPOSE: The objective of
      this study was to determine if improvement of the signs and symptoms of
      postoperative wound infection after spinal surgery correlates with a decrease in
      serum CRP and ESR while intravenous antibiotics are administered. STUDY DESIGN:
      Retrospective review. PATIENT SAMPLE: The study consisted of 21 patients (mean
      age 63.8 years; 13 female, 8 male) with postoperative wound infections after
      spinal surgery. They were studied for a minimum of 20 weeks. OUTCOME MEASURES:
      CRP and ESR were measured at the time of diagnosis and at serial time-points.
      METHODS: All patients received intravenous antibiotic therapy for 6-8 weeks.
      Patients were monitored for clinical signs and symptoms of infection such as
      fever, drainage, erythema, or a need for continued wound packing at 4, 7, and 20
      weeks after being diagnosed with a wound infection. RESULTS: The average CRP for
      all 21 patients at time of diagnosis was 11.7+/-9.0 mg/dL (range 1.2 to 37.8
      mg/dL). At the 4-week time-point, 16 patients ("early responders") showed
      clinical improvement with no fevers, no wound drainage, no erythema, and no need
      for wound packing. The average CRP of this group at the 4-week time-point
      decreased to 0.3+/-0.5 mg/dL. In contrast, at the 4-week time-point five patients
      ("late responders") still had signs and symptoms of infection (2 with continuing
      drainage requiring wound packing; 1 with vertebral osteomyelitis requiring
      irrigation and debridement; 2 with erythema without fevers). The average CRP for
      this group was still elevated at the 4-week time-point at 7.3+/-3.5 mg/dL. The
      CRP value difference was statistically significant between the two groups
      (p<.05). As treatment continued, at the 20-week time-point the average CRP of the
      late responders gradually decreased to 0.8+/-0.8 mg/dL, which was not
      statistically different from that of the early responders (average CRP=0.6+/-1.1
      mg/dL). All 21 patients had resolution of infection at the 20-week time-point.
      The ESR did not correlate well with clinical improvement. At time of diagnosis,
      the ESR of both early responders (average=57.6+/-27.6 mm/hr) and late responders
      (average=64.0+/-21.9 mm/hr) was elevated. It remained elevated for both groups
      from the beginning of the study to the end at all time-points. The final ESR at
      the 20-week time-point was not different between the early responders and late
      responders (average=27.6+/-22.3 mm/hr vs. 31.0+/-2.6 mm/hr, respectively; p>.05).
      CONCLUSIONS: Our data suggest that CRP may be of value in following the treatment
      response to antibiotics in wound infections after spinal surgery. The ESR can
      remain elevated in the presence of a normal CRP despite a resolution of clinical
      signs and symptoms of postoperative wound infection.

PMID- 16651227
TI  - Screening for depressive symptoms in patients with chronic spinal pain using the
      SF-36 Health Survey.
AB  - BACKGROUND DATA: Depression is a common co-morbidity for patients with complaints
      of spinal pain, yet often goes undiagnosed in clinical practice. Depressed
      patients who are not identified do not receive a referral or recommendation for
      treatments that may help ease their total illness burden. Relative to the total
      outcomes of spine care this may increase costs, decrease overall functional
      outcomes, and limit patient satisfaction. Some spine care settings track
      functional outcomes using a general health status survey. Although a specific and
      reliable survey to detect depression could be employed, an additional survey
      would unnecessarily increase responder and analyst burdens if the general health
      status survey could be used instead. OBJECTIVE: To identify the Mental Component
      Summary (MCS) cutoff score from the Short Form 36-item Health Survey (SF-36) that
      best predicts a positive depression score as measured by the Center for
      Epidemiological Study-Depression Survey (CES-D). STUDY DESIGN: An analysis of the
      diagnostic properties of the SF-36 MCS Scale as a predictor of depressive
      symptoms as measured by the CES-D. OUTCOME MEASURES: The SF-36 is a general
      health survey that contains a MCS score that represents the psychological well
      being and general health perception of the respondent. This composite score is
      norm-based (mean = 50, SD = 10) with lower scores representing poorer health. The
      CES-D has been well-studied in patients with chronic pain complaints and was used
      as the gold standard for determining the MCS cutoff score. A CES-D score of 19 or
      greater was considered positive for depressive symptoms. PATIENT SAMPLE: All
      patients entering our facility routinely complete the SF-36. Between February
      2002 and October 2002, all patients scoring 30 or less on the MCS (MCS < or = 30)
      also completed the CES-D. Patients who scored 2 standard deviations below the
      mean (MCS = 30 or less) were considered most at risk for depression. Patients
      scoring above 30 on their MCS (MCS > 30) were considered less likely to have
      depressive symptoms and were randomly chosen to complete the CES-D. There were
      420 patients who completed both surveys of which there were 99 MCS < or = 30
      patients and 321 MCS > 30 patients. METHODS: Receiver operating characteristic
      (ROC) curves were used to assess the sensitivity and specificity of the SF-36 as
      a screening tool for detecting depressive symptoms. RESULTS: An MCS score of 35
      has a sensitivity of 80% (76-83; 95% confidence interval), a specificity of 90%
      (87-93), an ROC area of 0.8517 (0.81-0.89), and correctly identified 87% of the
      sample. CONCLUSION: The SF-36 provides the benefits of a general functional
      health status measure and additionally appears to provide a screening tool for
      depressive symptoms. A cutoff score of 35 or less on the MCS scale has a high
      degree of sensitivity and specificity and is able to identify depressive symptoms
      in patients with back pain, which can help identify patients who will benefit
      from mental health treatments.

PMID- 16651228
TI  - Noncontiguous dual segment thoracic brucellosis with neurological deficit.
AB  - BACKGROUND CONTEXT: Brucellosis can affect the musculoskeletal system, and bony
      involvement ranges from 2% to 70% in the literature. Spinal brucellosis is
      generally localized to the sacroiliac region; thoracic brucellosis is rarely
      seen. PURPOSE: To present a case with noncontiguous multilevel thoracic
      brucellosis with spinal cord compression. STUDY DESIGN: Case report. METHODS: The
      patient underwent aggressive surgical debridement (posterior decompression,
      fusion and stabilization, and two noncontiguous level anterior corpectomy and
      fusion procedures with titanium mesh cages). RESULTS: At the latest follow-up of
      2 years, her clinical, radiological, and laboratory examination showed no
      recurrence of infection. The neurological examination was completely normal.
      CONCLUSION: Early aggressive debridement and stabilization together with medical
      treatment, especially in the elderly and immunocompromised patients, would be the
      most beneficial treatment for eradication of pathology.

PMID- 16651229
TI  - Paraparesis due to exacerbation of preexisting spinal pseudoarthrosis following
      infliximab therapy for advanced ankylosing spondylitis.
AB  - BACKGROUND CONTEXT: Recent reports have described the long-term efficacy and
      safety of infliximab as a treatment for ankylosing spondylitis (AS). The most
      important adverse effects of infliximab are infections, malignancies,
      autoimmunities, and hypersensitivity reactions. There has never been a reported
      case of paraparesis after infliximab therapy for AS. PURPOSE: To describe a case
      with paraparesis caused by rapid exacerbation of preexisting spinal
      pseudoarthrosis after infliximab therapy for advanced AS. STUDY DESIGN/SETTING:
      Case report/Osaka University Graduate School of Medicine, Suita, Japan. PATIENT
      SAMPLE: A 55-year-old man with a 27-year history of AS. OUTCOME MEASURES: Case
      report. METHODS: A 55-year-old man with a 27-year history of AS was treated with
      infliximab, which provided considerable pain relief and improvement of activities
      of daily living. However, as the patient resumed vigorous daily activity, he felt
      back pain and subsequently developed paraparesis. Radiographs showed rapid
      exacerbation of preexisting spinal pseudoarthrosis at the T11-T12 level after
      infliximab therapy. RESULTS: After laminectomy and posterolateral fusion, the
      back pain and paraparesis improved sufficiently to allow independent walking, but
      moderate bladder dysfunction persisted. CONCLUSIONS: Although this patient could
      have certainly become myelopathic over time without undergoing infliximab
      therapy, the patient's history and radiographic course suggest that suppression
      of inflammation by infliximab improved his activities of daily living, which
      paradoxically exacerbated preexisting spinal pseudoarthrosis and quickened the
      onset of subsequent myelopathy.

PMID- 16651230
TI  - Distraction injury to thoracic spine treated with thoracoscopic dual-rod
      fixation.
AB  - BACKGROUND CONTEXT: Thoracic hyperextension fracture-dislocation is a rare
      pattern of traumatic spinal injury, typically associated with gross spinal
      instability and severe neurological deficit. These extremely unstable injuries
      require internal fixation despite their potentially benign clinical presentation.
      PURPOSE: We present a patient with a thoracic distraction injury who remained
      neurologically intact. METHODS: The patient underwent thoracoscopic reduction and
      anterior fixation of the thoracic spine using a paired screw-rod construct.
      RESULTS: Postoperatively, the patient remained neurologically intact and had no
      complications related to his thoracic fixation and fusion. Follow-up radiographs
      showed maintenance of thoracic alignment and bony fusion. CONCLUSIONS: The
      endoscopic approach to the anterior thoracic spine was an excellent treatment
      option for this thoracic distraction injury.

PMID- 16651231
TI  - Methylprednisolone treatment in acute spinal cord injury: the myth challenged
      through a structured analysis of published literature.
AB  - BACKGROUND CONTEXT: Methylprednisolone has evolved during the 1990s, through the
      results obtained from the National Acute Spinal Cord Injury Studies NASCIS II and
      III, as a standard treatment in acute spinal injury. PURPOSE: To evaluate the
      scientific basic for the use of methylprednisolone in acute spinal cord injury.
      STUDY DESIGN: Systematic review of the accumulated literature. METHODS: Critical
      evaluation of the data obtained in the NASCIS II and III studies plus other
      accumulated literature. RESULTS: Analyses have been made on subgroups of the
      study populations, and the results were based on statistical artefacts.
      Furthermore, improved functional recovery shown by these studies was not
      clinically significant. CONCLUSION: There is insufficient evidence to support the
      use of methylprednisolone as a standard treatment in acute spinal cord injury.

PMID- 16651232
TI  - Intervertebral disc cyst.

PMID- 16651233
TI  - Quadriparesis following cervical epidural steroid injections.

PMID- 16651235
TI  - Proposal of a modified, treatment-oriented classification of odontoid fractures.

PMID- 16651236
TI  - The evaluation of blood donor deferral causes.
AB  - Safety of blood and blood products is a major problem all over the world.
      Screening for the markers of infectious diseases is an incomplete solution. One
      of the most important steps in improving the safety of blood and blood products
      is donor selection. In this study, causes of donor deferral were evaluated
      retrospectively in the blood center of a children's hospital. Analysis of the
      deferrals showed that the most commonly defined causes were recent sexual
      exposure in high-risk activity, recent ingestion of medication, low hemoglobin
      level, abnormal blood pressure, being underweight, tattoos, piercing or
      acupuncture in the preceding 6 months, recent history of infection and presenting
      for a subsequent donation too soon, elevation of transaminases, presence of the
      markers of the infectious diseases.

PMID- 16651237
TI  - Sickle cell intrahepatic cholestasis with cholelithiasis.
AB  - Sickle cell intrahepatic cholestasis (SCIC) is a rare complication seen in sickle
      cell patients who present with sudden onset of RUQ pain, progressive
      hepatomegaly, mild elevation of transaminases, coagulopathy, and extreme
      hyperbilirubinemia. Early recognition of this entity is essential to avoid life
      threatening complications. Diagnosis can be challenging given the overlap in
      clinical presentation with other conditions affecting the hepatobiliary biliary
      system in sickle cell anemia such as hepatitis, cholecystitis, and hepatic
      crisis. Treatment is currently limited to exchange transfusion. The authors
      present two patients with SCIC and cholelithiasis; the clinical picture of one is
      complicated by choledocholithiasis.

PMID- 16651238
TI  - Irinotecan for children with relapsed solid tumors.
AB  - Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen
      children with relapsed solid tumors received irinotecan 180 mg/m2/day for 3
      consecutive days, repeated once after 25 days off. Their original tumors were
      neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated
      sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1
      each. The average age at trials was 6 years. Partial response was achieved in 5
      (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated
      sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2.
      Irinotecan appears promising, and could become included in the first-line
      treatment.

PMID- 16651239
TI  - Acquired von Willebrand syndrome in a patient with Ewing sarcoma.
AB  - Acquired von Willebrand syndrome is a rare bleeding disorder with clinical and
      laboratory features closely resembling to hereditary von Willebrand disease. The
      syndrome may accompany various conditions, including malignant disorders, most
      often with Wilms tumor and adrenal cell carcinoma. In this report, the authors
      present a patient with AvWS in association with Ewing sarcoma for the first time
      in the literature. The abnormal bleeding tendency was successfully treated with
      fresh frozen plasma and did not recur after the first two courses of chemotherapy
      with clinical improvement.

PMID- 16651240
TI  - Identification of novel genes with prognostic value in childhood leukemia using
      cDNA microarray and quantitative RT-PCR.
AB  - The aim of this study was to identify genes distinctively expressed or suppressed
      in childhood leukemia with different prognoses, using cDNA microarray and
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). The
      expression levels of the selected genes by cDNA microarray were quantified in
      primary leukemic blasts from 44 patients (acute lymphoblastic leukemia, 28; acute
      myelogenous leukemia (AML), 13; transient myeloproliferative disorder, 3). The
      expression levels of CDKN2C, CRADD, and IGFBP-2 genes were significantly
      associated with the event-free survival of the patients in AML. The present
      results suggest that a combination of cDNA microarray and quantitative RT-PCR may
      be useful to identify novel genes with prognostic value in childhood AML.

PMID- 16651241
TI  - Long-term FVII substitution in a preterm infant with severe gastrointestinal
      bleeding and FVII deficiency due to a homozygous donor splice mutation IVS4+1G-
      >A.
AB  - Congenital FVII deficiency is a rare bleeding disorder. Clinical complications
      are similar to those seen in hemophilia A, and an increased incidence of
      intracerebral hemorrhage related to birth trauma has been reported. The authors
      report on an infant who presented at the second day of life with melaena and
      hematemesis caused by congenital FVII deficiency with minimal activity of 4%. A
      homozygous mutation IVS4+G-->A, formerly described in 2 siblings, who died of
      brain hemorrhage within the first month of life, was identified. Severe bleeding
      events were prevented with prophylactic treatment. Early identification of the
      underlying mutation helps to assess the risk of hemorrhage and prevent severe
      bleeding by prophylactic FVII therapy.

PMID- 16651242
TI  - Hungarian experience with Langerhans cell histiocytosis in childhood.
AB  - The Langerhans cell histiocytosis (LCH) in children is relatively rare and the
      long-term analysis of therapy results has not been done yet in Hungary. The aim
      of this study was to investigate the incidence, clinical features, prognostic
      risk factors, and treatment results of children's LCH in Hungary in a 20-year
      period. Children less than 18 years of age with newly diagnosed LCH in Hungary
      were entered in this study. Clinical data of all children with LCH were reported
      to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The
      clinical files were collected and abstracted for information regarding age at
      diagnosis, gender, disease characteristics, treatment, and outcome of treatment.
      Median follow-up duration of surviving patients is 10.98 years. Between January
      1981 and December 2000, 111 children under 18 years of age were newly diagnosed
      with LCH in Hungary. The annual incidence of LCH in children younger than 18
      years of age was 2.24/million children. The male-female ratio was 1.36:1; the
      mean age was 4 years 11 months. Thirty-eight children had localized disease and
      in 73 cases systemic dissemination was found already at the time of diagnosis.
      Twenty-two patients were treated only by local surgery, 7 by surgery with local
      irradiation, and 5 children got only local irradiation. In 2 cases remission was
      achieved with local steroid administration. Seventy-five patients received
      chemotherapy. In the 20 years of the study 14 children died, 9 due to the
      progression of the disease. Sixteen patients had relapse with a mean of 2.16 +/-
      1.29 years after the first diagnosis. Three patients with relapse got
      chemotherapy generally used in lymphoma and remission was achieved. The overall
      survival of all patients (n = 111) was 88.3 +/- 3.1% at 5 years and 87.3 +/- 3.2%
      at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival
      rate is high. Even disseminated diseases have a quite good prognosis in
      childhood.

PMID- 16651243
TI  - Which one is a risk factor for chemotherapy-induced febrile neutropenia in
      childhood solid tumors: early lymphopenia or monocytopenia?
AB  - Neutropenia is one of the undesirable effects of cancer chemotherapy, sometimes
      causing life-threatening events. The present study was conducted to identify the
      risk factors of neutropenia caused by chemotherapy. Between January 2001 and
      March 2004, a total of 77 children with 165 neutropenic attacks were enrolled in
      this study. Complete blood count was performed before chemotherapy and on days 1,
      3, 5, 7, and 9 consecutively. The complete blood count results of the febrile
      neutropenia (FN) group were compared to those of the non-FN group. The incidence
      of FN was significantly higher in patients with ANC counts < or =0.5 x 10(9)/L on
      days 3, 5, and 7, lymphocyte counts < or =0.5 x 10(9)/L on days 7 and 9, < or
      =0.7 x 10(9)/L on days 5, 7, and 9, and with monocyte counts < or =0.15 x 10(9)/L
      on days 7 and 9, respectively. Further statistical analysis showed that
      lymphocyte count < or =0.7 x 10(9)/L on day 5, and monocyte count < or =0.15 x
      10(9)/L on day 7 were independent risk factors for FN. The authors conclude that
      lymphocyte counts on the 5th day can be more a predictive factor than monocyte
      count.

PMID- 16651244
TI  - Successful treatment of multifocal unresectable hepatoblastoma with chemotherapy
      only.
AB  - We report the case of a girl with multi-focal hepatoblastoma in whom chemotherapy
      alone has resulted in long term event-free survival and possibly cure, without
      any surgical procedure apart from biopsy for initial diagnosis. At presentation
      she had a large tumour arising from the left lobe of liver and two other separate
      masses were noted in the right lobe, but the lungs were free of metastases.
      Histology showed a foetal type of hepatoblastoma. The serum alpha-feto protein
      (AFP) level was 44,000 iu/litre. Chemotherapy was started using the triple drug
      regime recommended for "high risk" (of relapse) patients in the SIOPEL 2
      hepatoblastoma protocol of the International Society of Paedaitric Oncology
      (SIOP). Within a few weeks her abdominal girth decreased, the child became much
      more comfortable. Drug-induced cardiotoxicity, ototoxicity and nephrotoxicity
      were not observed. After a total of 4 courses of chemotherapy (completed at the
      end of August 1998) a CT scan showed that all 3 tumours were smaller but that
      there were residual multifocal defects in the liver neither hepatic resection nor
      liver transplantation were considered safe or appropriate. 6.5 years after
      completion of chemotherapy and now aged 8.5 years the child is in normal health
      and at school with normal liver size, serum AFP levels and chest imaging.

PMID- 16651245
TI  - No effect of high-doses-methotrexate treatment on serum cardiac troponin I levels
      in children.

PMID- 16651246
TI  - Invasive fungal infections in children with hematological malignancies: a 5-year
      study.

PMID- 16651247
TI  - Methyl jasmonate treatment of mature Norway spruce (Picea abies) trees increases
      the accumulation of terpenoid resin components and protects against infection by
      Ceratocystis polonica, a bark beetle-associated fungus.
AB  - When conifers such as Picea abies Karst. (Norway spruce) are attacked by insects
      or pathogens, they often respond by producing increased quantities of terpenoid
      oleoresin. This response can be mimicked in young P. abies seedlings by treatment
      with methyl jasmonate (MJ). In this study, we determined the effects of MJ on
      terpenoids and other chemical defenses of mature P. abies, and investigated
      whether this treatment protected trees against attack by the blue-stain fungus
      Ceratocystis polonica (Siem.) C. Moreau, the most important fungal associate of
      the spruce bark beetle Ips typographus L. Methyl jasmonate treatment induced the
      formation of traumatic resin ducts in the developing xylem, enhanced resin flow
      and stimulated increased accumulation of monoterpenes, sesquiterpenes and
      diterpene resin acids. However, only minor changes were detected in terpene
      composition in response to MJ treatment and no changes in soluble phenolic
      concentration were measured. There was much variability in the timing and degree
      of response to MJ among clones. The observed chemical and anatomical changes in
      response to MJ treatment were correlated with increased resistance to C.
      polonica, suggesting that terpenoid oleoresin may function in defense against
      this pathogen.

PMID- 16651248
TI  - Physiology and anatomy of lenticel-like structures on leaves of Eucalyptus nitens
      and Eucalyptus globulus seedlings.
AB  - Intumescences or abnormal, non-pathogenic, blister-like protuberant growths, form
      on Eucalyptus globulus Labill. and, to a much lesser extent, Eucalyptus nitens
      (Deane and Maiden) Maiden leaves when plants are grown in a high relative
      humidity environment. We examined the histology of intumescences and their
      effects on leaf photosynthetic processes. Intumescences were induced by placing
      E. globulus and E. nitens seedlings in a relative humidity of 80% in a greenhouse
      for 5 days. Symptomatic and asymptomatic leaves of plants with intumescence
      development were compared with leaves of control plants. Light-saturated carbon
      dioxide (CO(2)) assimilation (A(max)) and responses of CO(2) assimilation (A) to
      varying intercellular CO(2) partial pressure (C(i)) were measured. Symptomatic
      and asymptomatic leaf samples were fixed and sectioned and cellular structure was
      examined. Intumescences greatly reduced the photosynthetic capacity of E.
      globulus leaves and were associated with reduced electron transport rate and
      ribulose bisphosphate (RuBP) regeneration capacity. Tissue necrotization and
      cellular collapse of the palisade mesophyll and deposition of phenolic compounds
      in the affected areas, probably reduced light penetration to photosynthesizing
      cells as well as reducing the amount of photosynthesizing tissue. Photosynthetic
      capacity of E. nitens was unaffected. The intumescences resembled simple
      lenticels, both morphologically and developmentally. To our knowledge, this is
      the first time that lenticel-like structures developed in response to
      environmental conditions have been described on leaves.

PMID- 16651249
TI  - Protein phosphatases 1 and 2A and the regulation of calcium uptake and pollen
      tube development in Picea wilsonii.
AB  - To investigate the roles of protein phosphatases 1 and 2A in the development of
      pollen tubes of Picea wilsonii Mast., pollen grains were cultured in standard
      medium in the presence and absence of the protein phosphatase inhibitors okadaic
      acid and calyculin A. At nanomolar concentrations, these compounds blocked pollen
      tube growth, causing abnormal morphologies of the pollen tubes. Studies with Fluo
      3 revealed that the inhibitors reduced the pollen-tube tip-to-base cytoplasmic
      calcium (Ca(2+)) gradient and arrested extracellular Ca(2+) uptake. The
      transmission electron microscope observations indicated that the fusion of
      paramural bodies with plasma membranes occurred frequently in the tip and sub-tip
      regions of control pollen tubes, but fusion rarely occurred in inhibitor-treated
      pollen tubes. Staining with aniline blue showed that callose accumulated in the
      tip regions of inhibitor-treated pollen tubes. Immunolabeling of pollen tubes
      revealed that acidic pectin epitopes recognized by the monoclonal antibody JIM5
      were present in the tip region and on the flanks of the sub-tip in normal pollen
      tubes. In inhibitor-treated pollen tubes, these epitopes existed only in the
      extreme tip region and at higher concentrations than in control pollen tubes. The
      esterified pectin recognized by JIM7 was located preferentially at the extreme
      tip region in normal pollen tubes, but at basal sites in inhibitor-treated tubes.
      Fourier transform infrared (FTIR) analysis further confirmed the changes in
      acidic and esterified pectin distributions and their relative contents. These
      results suggest that protein phosphatase 1 or 2A, or both, are involved in the
      regulation of Ca(2+) uptake across the plasma membrane, in exocytotic activity
      and in the biosynthesis of cell wall components, all processes that occur in the
      tip region of pollen tubes and that control pollen tube development.

PMID- 16651250
TI  - Critical night length for bud set and its variation in two photoperiodic ecotypes
      of Betula pendula.
AB  - We studied the variation in critical night length for bud set in two
      photoperiodic ecotypes (two latitudinally distant stands) of silver birch (Betula
      pendula Roth) in three phytotron experiments. Seeds from 21 open-pollinated
      mother trees in a southern (Tuusula, 60 degrees N) and a northern (Kittila, 67
      degrees N) Finnish stand were germinated and grown for 4 weeks in a 24-h
      photoperiod in a greenhouse and then moved to different night length treatments
      at 18 degrees C for 4 to 6 weeks. Night lengths from 5 to 8.5 h were used for
      southern origin seedlings and from 1 to 4.5 h for northern origin seedlings. At
      the end of the treatments, apical bud set was observed and the percentage of
      seedlings with bud set calculated for each treatment and tree progeny. The
      critical night lengths (CNL) for 50% bud set were determined separately for
      seedlings from each mother tree by regression analysis. In both ecotypes, the
      mean percentage of seedlings with bud set was lowest for the shortest night
      lengths and increased rapidly as night lengths increased. Mean CNL with its 95%
      confidence interval for the southern and northern ecotypes was 6.3 +/- 0.2 and
      3.1 +/- 0.3 h, respectively. The CNL of the two ecotypes differed significantly
      in three experiments. Within-ecotype variance of the CNL was significantly higher
      in the northern ecotype (0.484) than in the southern ecotype (0.150). Significant
      differences in CNL were detected between individual mother trees of the southern
      ecotype, but not between mother trees of the northern ecotype. The ranking of
      individual mother trees, based on CNL, differed in the three experiments.

PMID- 16651251
TI  - Carbohydrate transfer through root grafts to support shaded trees.
AB  - We investigated whether root grafts between lodgepole pine (Pinus contorta var.
      latifolia Dougl. ex. Loud.) trees can transfer sufficient carbohydrate reserves
      from a source tree to a grafted sink tree to affect the vigor of trees growing in
      a light-limited environment. Eleven plots were established in early spring and
      two grafted tree pairs and two independent non-grafted trees were selected at
      each plot. One tree in a grafted pair and one non-grafted tree were shaded at
      each plot, whereas the remaining trees were non-shaded during the experimental
      period. Shaded trees had significantly lower carbohydrate reserves and smaller
      crowns than non-shaded trees following one growing season. Grafted shaded trees
      had significantly higher root total nonstructural carbohydrate concentrations
      than non-grafted shaded trees, indicating that root grafts partially offset the
      effects of shading. Also, large root grafts transferred proportionately more
      carbohydrates to the shaded trees than small root grafts. Carbohydrates
      transferred through root grafts could allow grafted trees to persist under
      conditions where non-grafted trees would be removed by competition.

PMID- 16651252
TI  - Seasonal variations in water relations in current-year leaves of evergreen trees
      with delayed greening.
AB  - We investigated seasonal patterns of water relations in current-year leaves of
      three evergreen broad-leaved trees (Ilex pedunculosa Miq., Ligustrum japonicum
      Thunb., and Eurya japonica Thunb.) with delayed greening in a warm-temperate
      forest in Japan. We used the pressure-volume method to: (1) assess the extent to
      which seasonal variation in leaf water relations is attributable to leaf
      development processes in delayed greening leaves versus seasonal variation in
      environmental variables; and (2) investigate variation in leaf water relations
      during the transition from the sapling to the adult tree stage. Leaf mass per
      unit leaf area was generally lowest just after completion of leaf expansion in
      May (late spring), and increased gradually throughout the year. Osmotic potential
      at full turgor (Psi(o) (ft)) and leaf water potential at the turgor loss point
      (Psi(w) (tlp)) were highest in May, and lowest in midwinter in all species. In
      response to decreasing air temperature, Psi(o) (ft) dropped at the rate of 0.037
      MPa degrees C(-1). Dry-mass-based water content of leaves and the symplastic
      water fraction of total leaf water content gradually decreased throughout the
      year in all species. These results indicate that reductions in the symplastic
      water fraction during leaf development contributed to the passive concentration
      of solutes in cells and the resulting drop in winter Psi(o) (ft). The ratio of
      solutes to water volume increased in winter in current-year leaves of L.
      japonicum and E. japonica, indicating that osmotic adjustment (active
      accumulation of solutes) also contributed to the drop in winter in Psi(o) (ft).
      Bulk modulus of elasticity in cell walls fluctuated seasonally, but no general
      trend was found across species. Over the growing season, Psi(o) (ft) and Psi(w)
      (tlp) were lower in adult trees than in saplings especially in the case of I.
      pedunculosa, suggesting that adult-tree leaves are more drought and cold tolerant
      than sapling leaves. The ontogenetic increase in the stress resistance of I.
      pedunculosa may be related to its characteristic life form because I. pedunculosa
      grows taller than the other species studied.

PMID- 16651253
TI  - Relative shoot height and irradiance and the shoot and leaf properties of Quercus
      serrata saplings.
AB  - Effects of relative shoot height and irradiance on shoot and leaf properties of
      Quercus serrata Thunb. saplings growing in the understory and in gaps were
      investigated. Photosynthetic photon flux (PPF) at the location of the shoot
      relative to that in the open (relative PPF; rPPF) and the height of the shoot
      base relative to tree height (relative height; rHeight) were measured for all
      current-year shoots of each sapling. Current-year shoot properties (length, leaf
      area, number of daughter shoots) and mortality, and leaf properties (mass per
      area (LMA) and nitrogen content per area (N(area))) were examined in relation to
      rPPF and rHeight. N(area) was used as a proxy for area-based assimilative
      capacity. Shoot length, leaf area per shoot and number of daughter shoots
      increased with increasing rHeight, especially in well-lit conditions. Shoot
      mortality decreased with increasing rHeight and rPPF. Both LMA and N(area) were
      positively correlated with rPPF, but not rHeight.

PMID- 16651254
TI  - Soil-plant hydrology of indigenous and exotic trees in an Ethiopian montane
      forest.
AB  - Fast-growing exotic trees are widely planted in the tropics to counteract
      deforestation; however, their patterns of water use could be detrimental to
      overall ecosystem productivity through their impact on ecosystem water budget. In
      a comparative field study on seasonal soil-plant water dynamics of two exotic
      species (Cupressus lusitanica Mill. and Eucalyptus globulus Labill.) and the
      indigenous Podocarpus falcatus (Thunb.) Mirb. in south Ethiopia, we combined a
      2.5-year record for climate and soil water availability, natural-abundance oxygen
      isotope ratios (delta(18)O) of soil and xylem water, destructive root sampling
      and transpiration measurements. Soil was generally driest under C. lusitanica
      with its dense canopy and shallow root system, particularly following a
      relatively low-rainfall wet season, with the wettest soil under E. globulus. Wet
      season transpiration of C. lusitanica was twice that of the other species. In the
      dry season, P. falcatus and C. lusitanica reduced transpiration by a factor of
      six and two, respectively, whereas E. globulus showed a fivefold increase. In all
      species, there was a shift in water uptake to deeper soil layers as the dry
      season progressed, accompanied by relocation of live fine root biomass (LFR) of
      C. lusitanica and P. falcatus to deeper layers. Under P. falcatus, variability in
      soil matric potential, narrow delta(18)O depth gradients and high LFR indicated
      fast water redistribution. Subsoil water uptake was important only for E.
      globulus, which had low topsoil LFR and tap roots exploiting deep water. Although
      P. falcatus appeared better adapted to varying soil water availability than the
      exotic species, both conifers decreased growth substantially during dry weather.
      Growth of E. globulus was largely independent of topsoil water content, giving it
      the potential to cause substantial dry-season groundwater depletion.

PMID- 16651255
TI  - Co-occurring species differ in tree-ring delta(18)O trends.
AB  - The stable oxygen isotope ratio (delta(18)O) of tree-ring cellulose is jointly
      determined by the delta(18)O of xylem water, the delta(18)O of atmospheric water
      vapor, the humidity of the atmosphere and perhaps by species-specific differences
      in leaf structure and function. Atmospheric humidity and the delta(18)O of water
      vapor vary seasonally and annually, but if the canopy atmosphere is well mixed,
      atmospheric characteristics should be uniform among co-occurring trees. In
      contrast, xylem water delta(18)O is determined by the delta(18)O of water being
      drawn from the soil, which varies with depth. If co-occurring trees draw water
      from different soil depths, this soil-water delta(18)O signal would be manifest
      as differences in delta(18)O among the trees. We examined the variation in tree
      ring delta(18)O, over eight decades during the 20th Century, among three species
      co-occurring in natural forest stands of the northern Rocky Mountains in the USA.
      We sampled 10 Douglas-firs (Pseudotsuga menziesii (Mirb.) Franco var. glauca), 10
      ponderosa pines (Pinus ponderosa Laws.) and seven western white pines (Pinus
      monticola Dougl.). As expected, variation in atmospheric conditions was recorded
      in the delta(18)O of the cellulose produced in a given year, but observed
      climatic correlations with delta(18)O were weak. Significant correlations with
      June climate data included: daily maximum temperature (r = 0.29), daily minimum
      temperature (r = -0.25), mean temperature (r = 0.20), mean daily precipitation (r
      = -0.54), vapor pressure deficit (r = 0.32) and solar radiation (r = 0.44).
      Lagged effects were observed in Douglas-fir and western white pine. In these
      species, the delta(18)O of a given annual ring was correlated with the delta(18)O
      of the previous ring. Ponderosa pine showed no significant autocorrelation.
      Although the species means were correlated among years (r = 0.67 to 0.76),
      ponderosa pine was consistently enriched in delta(18)O relative to the other
      species; differences were close to 2 per thousand and they are steadily
      increasing. Relative to the mean for the three species, ponderosa pine is
      becoming steadily more enriched (-1.0 per thousand). In contrast, Douglas-fir is
      being steadily depleted and western pine is intermediate, with an enrichment of
      0.5 per thousand. Because all trees were exposed to the same atmospheric
      conditions, the differences in delta(18)O observed between species are likely due
      either to differences in the depth of water extraction or leaf function. If the
      former, presumably ponderosa pine has steadily taken up more water from near the
      soil surface and Douglas-fir has shifted uptake to a greater depth. If the
      latter, we suggest the pronounced changes in leaf-water delta(18)O are a result
      of changes in leaf structure and function with tree size and age.

PMID- 16651256
TI  - Carbonic anhydrase in Tectona grandis: kinetics, stability, isozyme analysis and
      relationship with photosynthesis.
AB  - Carbonic anhydrase (CA, EC: 4.2.1.1) activity in teak (Tectona grandis L.f.) was
      studied to determine its characteristics, kinetics and isozyme patterns. We also
      investigated effects of leaf age, plant age and genotype on CA activity and gas
      exchange parameters. Carbonic anhydrase extracted from leaves in 12 mM veronal
      buffer, pH 7.8, had a K(m) for CO(2) of 15.20 mM and a V(max) of 35,448 U mg(-1)
      chlorophyll min(-1), which values declined by 50 and 70%, respectively, after 1
      week of storage at 4 degrees C. A 15% native polyacrylamide gel revealed the
      absence of CA isozymes in teak, with only a single CA band of 45 kD molecular
      mass observed across 10 segregating half-sib families and groups of trees ranging
      in age from 10 to 25 years. Activity remained stable during the first month in
      storage at 0 degrees C, but gradually declined to 25% of the initial value after
      1 year in storage. During the period of active growth (February-May), maximal CA
      activity was observed in fully expanded and illuminated leaves. Significant
      variation was observed in CA activity across 10 1-year-old half-sib families and
      21 5-year-old half-sib families. There was a positive correlation between CA
      activity and photosynthetic rate in a population of 10-year-old trees (P <
      0.005). Positive correlations between CA activity and photosynthetic rate were
      found in 10 of 21 5-year-old half-sib families (P < 0.005 to P < 0.05), which
      showed greater diversity in CA activity than in photosynthetic characteristics.
      Thus, CA may serve as a biochemical marker for photosynthetic capacity in teak
      genotypes.

PMID- 16651257
TI  - Optical properties of bud scales and protochlorophyll(ide) forms in leaf
      primordia of closed and opened buds.
AB  - The transmission spectra of bud scales of 14 woody species and the 77 K
      fluorescence emission spectra of the innermost leaf primordia of closed and
      opened buds of 37 woody species were studied. Pigment concentrations were
      determined in some species. Bud scales had low transmittance between 400 and 680
      nm with a local minimum around 680 nm. Transmittance increased steeply above 680
      nm and was > 80% in the 700-800 nm spectral region. Significant
      protochlorophyllide (Pchlide) accumulation was observed in leaf primordia of
      tightly packed, closed buds with relatively thick, dark bud scales. In common ash
      (Fraxinus excelsior L.) and Hungarian ash (Fraxinus angustifolia Vahl.), the
      innermost leaf primordia of the closed buds contained protochlorophyll (Pchl) and
      Pchlide (abbreviated as Pchl(ide)), but no chlorophyll. We observed Pchl(ide)
      forms with emission maxima at 633, 643 and 655 nm in these leaves. Complete
      transformation of Pchlide(655) (protochlorophyllide form with maximum emission at
      655 nm) into Chlide(692) (chlorophyllide form with maximum emission at 692 nm)
      occurred after irradiation for 10 s. The innermost leaf primordia of the buds of
      four species (flowering ash (Fraxinus ornus L.), horse chestnut (Aesculus
      hippocastanum L.), tree of heaven (Ailanthus altissima P. Mill.) and common
      walnut (Juglans regia L.)) contained Pchl(ide)(633), Pchl(ide)(643) and
      Pchlide(655) as well as an emission band at 688 nm corresponding to a chlorophyll
      form. The Pchlide(655) was fully photoactive in these species. The outermost leaf
      primordia of these four species and the innermost leaf primordia of 28 other
      species contained all of the above described Pchl(ide) forms in various ratios
      but in small amounts. In addition, Chl forms were present and the main bands in
      the fluorescence emission spectra were at 690 or 740 nm, or both. The results
      indicate that Pchl(ide) accumulation occurs in leaf primordia in near darkness
      inside the tightly closed buds, where the bud scales and the external leaf
      primordia function as optical filters.

PMID- 16651258
TI  - Transient etiolation: protochlorophyll(ide) and chlorophyll forms in
      differentiating plastids of closed and breaking leaf buds of horse chestnut
      (Aesculus hippocastanum).
AB  - An accompanying paper reports the accumulation of photoactive protochlorophyllide
      (Pchlide) in the innermost leaf primordia of buds of many tree species. In this
      paper, we describe plastid differentiation, changes in pigment concentrations and
      spectral properties of bud scales and leaf primordia of horse chestnut (Aesculus
      hippocastanum L.) from January until the end of bud break in April. The bud
      scales contained plastids with grana, stroma thylakoids characteristic of
      chloroplasts and large dense bodies within the stroma. In January, proplastids
      and young chloroplasts were present in the leaf primordia, and the fluorescence
      spectra of the primordia were similar to those of green leaves except for a minor
      band at 630 nm, indicative of a protochlorophyll(ide). During bud break, the
      pigment concentrations of the green bud scales and the outermost leaf primordia
      increased, and Pchlide forms with emission maxima at 633, 644 and 655 nm
      accumulated in the middle and innermost leaf primordia. Depending on the position
      of the leaf primordia within the bud, their plastids and their pigment
      concentrations varied. Etio-chloroplasts with prolamellar bodies (PLBs) and
      prothylakoids with developing grana were observed in the innermost leaves.
      Besides the above-mentioned Pchlide forms, the middle and innnermost leaf
      primordia contained only a Chl band with an emission maximum at 686 nm. The
      outermost leaf primordia contained etio-chloroplasts with well-developed grana
      and small, narrow-type PLBs. These outermost leaves contained only chlorophyll
      forms like the mature green leaves. No Pchlide accumulation was observed after
      bud break, indicating that etiolation of the innermost and middle leaves is
      transient. The Pchlide forms and the plastid types of the primordia in buds grown
      in nature were similar to those of leaves of dark-germinated seedlings and to
      those of the leaf primordia of dark-forced buds. We conclude that transient
      etiolation occurs under natural conditions. The formation of PLBs and etio
      chloroplasts and the accumulation of the light-dependent
      NADPH:protochlorophyllide oxidoreductase are involved in the natural greening
      process and ontogenesis of young leaf primordia of horse chestnut buds.

PMID- 16651259
TI  - Seasonal variation in photosystem II efficiency and photochemical reflectance
      index of evergreen trees and perennial grasses growing at low and high elevations
      in subtropical Taiwan.
AB  - Three pines species, three evergreen broadleaf trees, one C(3) and two C(4)
      perennial grasses of subtropical Taiwan were studied to elucidate the correlation
      between photosystem II (PSII) efficiency and photochemical reflectance index (PRI
      = (R(531) - R(570))/(R(531) + R(570))). Measurements were made at two sites
      differing in altitude (800 and 2600 m) over several growing seasons. At high
      elevation, potential PSII efficiency, measured by chlorophyll fluorescence (the
      ratio of variable to maximal fluorescence; F(v)/F(m)) at predawn, decreased with
      decreasing air temperature and varied greatly among species. At the lowest air
      temperature (-3 degrees C) studied, variation in F(v)/F(m) among species ranged
      from 0.33 to 0.72. In contrast, at low elevation where air temperature was
      moderate, seasonal variation in F(v)/F(m) was small in all of the study species.
      When species, elevation and season data were pooled, despite the high variation
      in F(v)/F(m) among species, a good correlation between F(v)/F(m) and PRI was
      observed. When compared at the same value of PRI, F(v)/F(m) of evergreen trees
      was higher than that of perennial grasses; however, when the minimum temperature
      on the measurement day was below 0 degrees C, F(v)/F(m) was underestimated
      relative to PRI. We conclude that PRI could be used as a remote indicator of
      photosynthetic function when air temperature is above 0 degrees C.

PMID- 16651260
TI  - Protein kinase D intracellular localization and activity control kinase D
      interacting substrate of 220-kDa traffic through a postsynaptic density-95/discs
      large/zonula occludens-1-binding motif.
AB  - Protein kinase D (PKD) controls protein traffic from the trans-Golgi network
      (TGN) to the plasma membrane of epithelial cells in an isoform-specific manner.
      However, whether the different PKD isoforms could be selectively regulating the
      traffic of their specific substrates remains unexplored. We identified the C
      terminus of the different PKDs that constitutes a postsynaptic density-95/discs
      large/zonula occludens-1 (PDZ)-binding motif in PKD1 and PKD2, but not in PKD3,
      to be responsible for the differential control of kinase D-interacting substrate
      of 220-kDa (Kidins220) surface localization, a neural membrane protein identified
      as the first substrate of PKD1. A kinase-inactive mutant of PKD3 is only able to
      alter the localization of Kidins220 at the plasma membrane when its C terminus
      has been substituted by the PDZ-binding motif of PKD1 or PKD2. This isoform
      specific regulation of Kidins220 transport might not be due to differences among
      kinase activity or substrate selectivity of the PKD isoenzymes but more to the
      adaptors bound to their unique C terminus. Furthermore, by mutating the
      autophosphorylation site Ser(916), located at the critical position -2 of the PDZ
      binding domain within PKD1, or by phorbol ester stimulation, we demonstrate that
      the phosphorylation of this residue is crucial for Kidins220-regulated transport.
      We also discovered that Ser(916) trans-phosphorylation takes place among PKD1
      molecules. Finally, we demonstrate that PKD1 association to intracellular
      membranes is critical to control Kidins220 traffic. Our findings reveal the
      molecular mechanism by which PKD localization and activity control the traffic of
      Kidins220, most likely by modulating the recruitment of PDZ proteins in an
      isoform-specific and phosphorylation-dependent manner.

PMID- 16651261
TI  - Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for
      inverting 4,6-dehydratase activity.
AB  - FlaA1 from the human pathogen Helicobacter pylori is an enzyme involved in
      saccharide biosynthesis that has been shown to be essential for pathogenicity.
      Here we present five crystal structures of FlaA1 in the presence of substrate,
      inhibitors, and bound cofactor, with resolutions ranging from 2.8 to 1.9 A. These
      structures reveal that the enzyme is a novel member of the short-chain
      dehydrogenase/reductase superfamily. Additional electron microscopy studies show
      the enzyme to possess a hexameric doughnut-shaped quaternary structure. NMR
      analyses of "real time" enzyme-substrate reactions indicate that FlaA1 is a UDP
      GlcNAc-inverting 4,6-dehydratase, suggesting that the enzyme catalyzes the first
      step in the biosynthetic pathway of a pseudaminic acid derivative, which is
      implicated in protein glycosylation. Guided by evidence from site-directed
      mutagenesis and computational simulations, a three-step reaction mechanism is
      proposed that involves Lys-133 functioning as both a catalytic acid and base.

PMID- 16651262
TI  - Role of heme-protein covalent bonds in mammalian peroxidases. Protection of the
      heme by a single engineered heme-protein link in horseradish peroxidase.
AB  - Oxidation of SCN-, Br-, and Cl- (X-) by horseradish peroxidase (HRP) and other
      plant and fungal peroxidases results in the addition of HOX to the heme vinyl
      group. This reaction is not observed with lactoperoxidase (LPO), in which the
      heme is covalently bound to the protein via two ester bonds between carboxylic
      side chains and heme methyl groups. To test the hypothesis that the heme of LPO
      and other mammalian peroxidases is protected from vinyl group modification by the
      hemeprotein covalent bonds, we prepared the F41E mutant of HRP in which the heme
      is attached to the protein via a covalent bond between Glu41 and the heme 3
      methyl. We also examined the E375D mutant of LPO in which only one of the two
      normal covalent heme links is retained. The prosthetic heme groups of F41E HRP
      and E375D LPO are essentially not modified by the HOBr produced by these enzymes.
      The double E375D/D225E mutant of LPO that can form no covalent bonds is inactive
      and could not be examined. These results unambiguously demonstrate that a single
      heme-protein link is sufficient to protect the heme from vinyl group modification
      even in a protein (HRP) that is normally highly susceptible to this reaction. The
      results directly establish that one function of the covalent heme-protein bonds
      in mammalian peroxidases is to protect their prosthetic group from their highly
      reactive metabolic products.

PMID- 16651263
TI  - Functional consequences of interactions between Pax9 and Msx1 genes in normal and
      abnormal tooth development.
AB  - Pax9 and Msx1 encode transcription factors that are known to be essential for the
      switch in odontogenic potential from the epithelium to the mesenchyme. Multiple
      lines of evidence suggest that these molecules play an important role in the
      maintenance of mesenchymal Bmp4 expression, which ultimately drives morphogenesis
      of the dental organ. Here we demonstrate that Pax9 is able to directly regulate
      Msx1 expression and interact with Msx1 at the protein level to enhance its
      ability to transactivate Msx1 and Bmp4 expression during tooth development. In
      addition, we tested how a missense mutation (T62C) in the paired domain of PAX9
      that is responsible for human tooth agenesis (1) affects its functions. Our data
      indicate that although the mutant Pax9 protein (L21P) can bind to the Msx1
      protein, it fails to transactivate the Msx1 and Bmp4 promoter, presumably because
      of its inability to bind cognate paired domain recognition sequences. In
      addition, synergistic transcriptional activation of the Bmp4 promoter was lost
      with coexpression of mutant Pax9 and wild-type Msx1. This suggests that Pax9 is
      critical for the regulation of Bmp4 expression through its paired domain rather
      than Msx1. Our findings demonstrate the partnership of Pax9 and Msx1 in a
      signaling pathway that involves Bmp4. Furthermore, the regulation of Bmp4
      expression by the interaction of Pax9 with Msx1 at the level of transcription and
      through formation of a protein complex determines the fate of the transition from
      bud to cap stage during tooth development.

PMID- 16651264
TI  - The solution structure of Escherichia coli Wzb reveals a novel substrate
      recognition mechanism of prokaryotic low molecular weight protein-tyrosine
      phosphatases.
AB  - Low molecular weight protein-tyrosine phosphatases (LMW-PTPs) are small enzymes
      that ubiquitously exist in various organisms and play important roles in many
      biological processes. In Escherichia coli, the LMW-PTP Wzb dephosphorylates the
      autokinase Wzc, and the Wzc/Wzb pair regulates colanic acid production. However,
      the substrate recognition mechanism of Wzb is still poorly understood thus far.
      To elucidate the molecular basis of the catalytic mechanism, we have determined
      the solution structure of Wzb at high resolution by NMR spectroscopy. The Wzb
      structure highly resembles that of the typical LMW-PTP fold, suggesting that Wzb
      may adopt a similar catalytic mechanism with other LMW-PTPs. Nevertheless, in
      comparison with eukaryotic LMW-PTPs, the absence of an aromatic amino acid at the
      bottom of the active site significantly alters the molecular surface and
      implicates Wzb may adopt a novel substrate recognition mechanism. Furthermore, a
      structure-based multiple sequence alignment suggests that a class of the
      prokaryotic LMW-PTPs may share a similar substrate recognition mechanism with
      Wzb. The current studies provide the structural basis for rational drug design
      against the pathogenic bacteria.

PMID- 16651265
TI  - A novel estradiol/estrogen receptor alpha-dependent transcriptional mechanism
      controls expression of the human prolactin receptor.
AB  - Prolactin exerts diverse functions in target tissues through its membrane
      receptors, and is a potent mitogen in normal and neoplastic breast cells.
      Estradiol (E(2)) induces human prolactin receptor (hPRLR) gene expression through
      stimulation of its generic promoter (PIII). This study identifies a novel E(2)
      regulated non-estrogen responsive element-dependent transcriptional mechanism
      that mediates E(2)-induced hPRLR expression. E(2) stimulated transcriptional
      activity in MCF7A(2) cells transfected with PIII lacking an estrogen responsive
      element, and increased hPRLR mRNA and protein. The abolition of the E(2) effect
      by mutation of Sp1 or C/EBP elements that bind Sp1/Sp3 and C/EBPbeta within PIII
      indicated the cooperation of these transfactors in E(2)-induced transcription of
      the hPRLR. DNA affinity protein assay showed that E(2) induced estrogen receptor
      alpha (ERalpha) binding to Sp1/Sp3 and C/EBPbeta DNA-protein complexes. The
      ligand-binding domain of ERalpha was essential for its physical interaction with
      C/EBPbeta, and E(2) promoted this association, and its DNA binding domain was
      required for transactivation of PIII. Co-immunoprecipitation studies revealed
      tethering of C/EBPbeta to Sp1 by E(2)-activated ERalpha. Chromatin
      immunoprecipitation analysis showed that E(2) induced recruitment of C/EBPbeta,
      ERalpha, SRC1, p300, pCAF, TFIIB, and Pol II, with no change in Sp1/Sp3. E(2)
      also induced promoter-associated acetylation of H3 and H4. These findings
      demonstrate that an E(2)/ERalpha, Sp1, and C/EBPbeta complex with recruitment of
      coactivators and TFIIB and Pol II are required for E(2)-activated transcriptional
      expression of the hPRLR through PIII. Estradiol produced in breast stroma and
      adipose tissue, which are major sources of estrogen in post-menopausal women,
      could up-regulate hPRLR gene expression and stimulate breast tumor growth.

PMID- 16651266
TI  - Roles of glutamate receptors and the mammalian target of rapamycin (mTOR)
      signaling pathway in activity-dependent dendritic protein synthesis in
      hippocampal neurons.
AB  - Local protein synthesis in neuronal dendrites is critical for synaptic
      plasticity. However, the signaling cascades that couple synaptic activation to
      dendritic protein synthesis remain elusive. The purpose of this study is to
      determine the role of glutamate receptors and the mammalian target of rapamycin
      (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We
      first characterized the involvement of various subtypes of glutamate receptors
      and the mTOR kinase in regulating dendritic synthesis of a green fluorescent
      protein (GFP) reporter controlled by alphaCaMKII 5' and 3' untranslated regions
      in cultured hippocampal neurons. Specific antagonists of N-methyl-d-aspartic acid
      (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and
      metabotropic glutamate receptors abolished glutamate-induced dendritic GFP
      synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate
      receptors activated GFP synthesis in dendrites. Inhibitions of the mTOR
      signaling, as well as its upstream activators, phosphatidylinositol 3-kinase and
      AKT, blocked NMDA receptor-dependent dendritic GFP synthesis. Conversely,
      activation of mTOR signaling stimulated dendritic GFP synthesis. In addition, we
      also found that inhibition of the mTOR kinase blocked dendritic synthesis of the
      endogenous alphaCaMKII and MAP2 proteins induced by tetanic stimulations in
      hippocampal slices. These results identify critical roles of NMDA receptors and
      the mTOR signaling pathway for control of synaptic activity-induced dendritic
      protein synthesis in hippocampal neurons.

PMID- 16651267
TI  - Phosphorylation of microtubule-associated protein STOP by calmodulin kinase II.
AB  - STOP proteins are microtubule-associated, calmodulin-regulated proteins
      responsible for the high degree of stabilization displayed by neuronal
      microtubules. STOP suppression in mice induces synaptic defects affecting both
      short and long term synaptic plasticity in hippocampal neurons. Interestingly,
      STOP has been identified as a component of synaptic structures in neurons,
      despite the absence of microtubules in nerve terminals, indicating the existence
      of mechanisms able to induce a translocation of STOP from microtubules to
      synaptic compartments. Here we have tested STOP phosphorylation as a candidate
      mechanism for STOP relocalization. We show that, both in vitro and in vivo, STOP
      is phosphorylated by the multifunctional enzyme calcium/calmodulin-dependent
      protein kinase II (CaMKII), which is a key enzyme for synaptic plasticity. This
      phosphorylation occurs on at least two independent sites. Phosphorylated forms of
      STOP do not bind microtubules in vitro and do not co-localize with microtubules
      in cultured differentiating neurons. Instead, phosphorylated STOP co-localizes
      with actin assemblies along neurites or at branching points. Correlatively, we
      find that STOP binds to actin in vitro. Finally, in differentiated neurons,
      phosphorylated STOP co-localizes with clusters of synaptic proteins, whereas
      unphosphorylated STOP does not. Thus, STOP phosphorylation by CaMKII may promote
      STOP translocation from microtubules to synaptic compartments where it may
      interact with actin, which could be important for STOP function in synaptic
      plasticity.

PMID- 16651268
TI  - Identification of the maturation factor for dual oxidase. Evolution of an
      eukaryotic operon equivalent.
AB  - Dual oxidase 2 (DUOX2), an NADPH:O(2) oxidoreductase flavoprotein, is a component
      of the thyroid H(2)O(2) generator crucial for hormone synthesis at the apical
      membrane. Mutations in DUOX2 produce congenital hypothyroidism in humans.
      However, no functional DUOX-based NADPH oxidase has ever been reconstituted at
      the plasma membrane of transfected cells. It has been proposed that DUOX
      retention in the endoplasmatic reticulum (ER) of heterologous systems is due to
      the lack of an unidentified component required for functional maturation of the
      enzyme. By data mining of a massively parallel signature sequencing tissue
      expression data base, we identified an uncharacterized gene named DUOX maturation
      factor (DUOXA2) arranged head-to-head to and co-expressed with DUOX2. A paralog
      (DUOXA1) was similarly linked to DUOX1. The genomic rearrangement leading to
      linkage of ancient DUOX and DUOXA genes could be traced back before the
      divergence of echinoderms. We demonstrate that co-expression of DUOXA2, an ER
      resident transmembrane protein, allows ER-to-Golgi transition, maturation, and
      translocation to the plasma membrane of functional DUOX2 in a heterologous
      system. The identification of DUOXA genes has important implications for studies
      of the molecular mechanisms controlling DUOX expression and the molecular
      genetics of congenital hypothyroidism.

PMID- 16651269
TI  - Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha
      D-phosphohexomutase superfamily, and its substrate and product complexes.
AB  - N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the
      synthetic process of UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a UDP
      sugar that serves as a biosynthetic precursor of glycoproteins,
      mucopolysaccharides, and the cell wall of bacteria. Thus, a specific inhibitor of
      AGM1 from pathogenetic fungi could be a new candidate for an antifungal reagent
      that inhibits cell wall synthesis. AGM1 catalyzes the conversion of N
      acetylglucosamine 6-phosphate (GlcNAc-6-P) into N-acetylglucosamine 1-phosphate
      (GlcNAc-1-P). This enzyme is a member of the alpha-D-phosphohexomutase
      superfamily, which catalyzes the intramolecular phosphoryl transfer of sugar
      substrates. Here we report the crystal structures of AGM1 from Candida albicans
      for the first time, both in the apoform and in the complex forms with the
      substrate and the product, and discuss its catalytic mechanism. The structure of
      AGM1 consists of four domains, of which three domains have essentially the same
      fold. The overall structure is similar to those of phosphohexomutases; however,
      there are two additional beta-strands in domain 4, and a circular permutation
      occurs in domain 1. The catalytic cleft is formed by four loops from each domain.
      The N-acetyl group of the substrate is recognized by Val-370 and Asn-389 in
      domain 3, from which the substrate specificity arises. By comparing the substrate
      and product complexes, it is suggested that the substrate rotates about 180
      degrees on the axis linking C-4 and the midpoint of the C-5-O-5 bond in the
      reaction.

PMID- 16651270
TI  - Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin
      ligase.
AB  - The Hedgehog (Hh) signaling pathway plays a crucial role in embryogenesis and has
      been linked to the development of several human malignancies. The transcription
      factor Gli2 plays a key role in the transduction of Hh signals by modulating
      transcription of some Hh target genes, yet the mechanisms that control Gli2
      protein expression are largely unknown. Here we report that beta-transducin
      repeat-containing protein (beta-TrCP) E3 ubiquitin ligase is required for Gli2
      degradation. beta-TrCP2 directly binds wild type Gli2 and promotes its
      ubiquitination. Single amino acid substitution in Gli2 putative binding site
      inhibits its interaction with beta-TrCP2, its ubiquitination, and stabilizes the
      Gli2 protein. Stable Gli2 mutant is expressed in higher levels and is more potent
      in the activation of Gli-dependent transcription as compared with wild type Gli2.
      We also found that GLI2 protein is expressed highly in prostate cancer cell lines
      and primary tumors, whereas the level of GLI2 mRNA is not appreciably different
      in normal and neoplastic prostate. These data identify beta-TrCP2 as a pivotal
      regulator of Gli2 expression and point to an important role for posttranslational
      modulation of GLI2 protein levels in Hh pathway-associated human prostate cancer.

PMID- 16651271
TI  - Assessing the potential for violent behavior in children and adolescents.

PMID- 16651272
TI  - Seizure-like states.

PMID- 16651273
TI  - Childhood drowning.

PMID- 16651274
TI  - Approach to acute limb pain in childhood.

PMID- 16651275
TI  - Body composition: salt and water.

PMID- 16651276
TI  - Index of suspicion.

PMID- 16651277
TI  - Principles of growth assessment.

PMID- 16651278
TI  - Endocarditis after closure of ventricular septal defect by transcatheter device.
AB  - Advances in interventional cardiology have enabled the treatment of severe
      congenital heart defects without the need for surgery. The percutaneous closure
      of atrial septal defects and, more recently, ventricular septal defects is
      considered a safe procedure with fewer complications and less morbidity compared
      with surgery. We report on a 2-year-old child who developed endocarditis after
      ventricular septal defect closure with an Amplatzer device. The patient recovered
      after intravenous antibiotics and anticoagulation. To the best of our knowledge,
      this is the first report of endocarditis associated with ventricular septal
      defect closure device insertion.

PMID- 16651279
TI  - Interferon-alpha treatment of molluscum contagiosum in a patient with
      hyperimmunoglobulin E syndrome.
AB  - We report widely disseminated molluscum contagiosum that occurred in a 9-year-old
      boy secondary to hyperimmunoglobulin E syndrome, a primary immunodeficiency
      disorder. Cutaneous examination revealed numerous, widespread, skin-colored to
      translucent, firm, umbilicated papules of varying sizes. They were distributed
      throughout the perineal and gluteal areas and bilaterally over his lower limbs. A
      biopsy specimen from his skin lesion demonstrated lobulated epidermal growth that
      consisted of keratinocytes with large intracytoplasmic eosinophilic inclusion
      bodies and a central crater. These findings were consistent with the diagnosis of
      molluscum contagiosum. Many treatments for his skin lesions were ineffective,
      including physical destruction or manual extrusion of the lesions; cryotherapy;
      curettage; and topical therapies with phenol, trichloroacetic acid, and
      imiquimod. The patient was treated successfully with subcutaneous interferon
      alpha for 6 months without any adverse effect.

PMID- 16651280
TI  - Air swallowing caused recurrent ileus in Tourette's syndrome.
AB  - This report describes an adolescent boy who has Tourette's syndrome and developed
      a subtle but significant increase in vocal tics after an 8-month respite. The
      increase in vocal tics was associated with an acute increase in psychological
      stressors and resulted in recurrent air swallowing, which, in turn, caused
      abdominal cramping, eructation, and flatus, eventually leading to aeroenteria.
      Air swallowing was recognized only after a second hospital admission for
      recurrent ileus. Air swallowing and associated symptoms were mitigated by
      reinstitution of psychopharmacologic treatment and an increase in the patient's
      self-awareness of the air-swallowing behavior. Clinically significant air
      swallowing has not been described previously in Tourette syndrome or a tic
      disorder. This case is important for pediatricians and pediatric
      gastroenterologists because either may be the first to evaluate a child or an
      adolescent with unexplained recurrent ileus. This report also documents the
      importance of the connection between the brain and the body.

PMID- 16651281
TI  - 2005 American Heart Association (AHA) guidelines for cardiopulmonary
      resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and
      neonatal patients: pediatric advanced life support.

PMID- 16651282
TI  - 2005 American Heart Association (AHA) guidelines for cardiopulmonary
      resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and
      neonatal patients: neonatal resuscitation guidelines.

PMID- 16651283
TI  - Findings in older children with abusive head injury: does shaken-child syndrome
      exist?
AB  - Shaken-baby syndrome (SBS) has been hypothesized to occur after shaking by an
      adult during the first 2 years of life. We wondered whether it is possible to
      achieve rotational forces sufficient to cause SBS-like injuries in children >2
      years of age. The present study describes cases of child abuse in older children
      who presented with the classic ophthalmologic and intracranial findings of SBS.
      In this case series, 4 cases of older children (2.5-7 years old; 11.8-22 kg) who
      died from abusive head injuries and who had diffuse retinal hemorrhages
      identified antemortem were selected for review. The cases were abstracted from
      hospital charts, records from autopsies, coroners' and district attorneys'
      offices, and court transcripts. In all 4 cases the history provided by the
      primary caregiver did not match the severity of the injuries. Three case subjects
      presented with patterned bruises. Multilayered retinal hemorrhages and acute
      subdural hematoma were observed in all 4 cases. At autopsy, diffuse axonal injury
      was evident in 3 of the 4 cases; all 4 cases had optic nerve sheath hemorrhages.
      None of the victims had skeletal fractures on radiologic examination or at
      autopsy. This case series demonstrates that it is possible to observe SBS-like
      retinal and central nervous system findings in the older and heavier child. Our
      findings underscore the need for providers to consider intentional shaking as a
      mechanism of injury in the evaluation of abusive head injury in older children.

PMID- 16651284
TI  - Persistent cough and failure to thrive: a presentation of foreign body aspiration
      in a child with asthma.
AB  - Severe failure to thrive (FTT) in a child with asthma and a persistent cough
      should not be explained solely by asthma and warrants a thorough and prompt
      evaluation. The finding of a foreign body in our case was surprising, because it
      does not usually present as or lead to FTT. Good clinical judgment and habits
      could prevent the course of events that we described in this case. Following are
      the key lessons to be learned from this presentation: (1) maintain a high index
      of suspicion for foreign body aspiration, even in toddlers with asthma, (2) pay
      special attention to a child with FTT, (3) be aware of localizing findings on
      physical examination and chest radiographs, and (4) perform a chest radiograph no
      later than after 1 month of chronic cough.

PMID- 16651285
TI  - Therapy with gastric acidity inhibitors increases the risk of acute
      gastroenteritis and community-acquired pneumonia in children.
AB  - OBJECTIVE: Gastric acidity (GA) inhibitors, including histamine-2 receptor
      antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of
      gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor
      induced hypochlorhydria has been suggested as a risk factor for severe
      gastrointestinal infections. In addition, a number of papers and a meta-analysis
      have shown an increased risk of pneumonia in H2-blocker-treated intensive care
      patients. More recently, an increased risk of community-acquired pneumonia
      associated with GA inhibitor treatment has been reported in a large cohort of
      adult patients. These findings are particularly relevant to pediatricians today
      because so many children receive some sort of GA-blocking agent to treat GERD. To
      test the hypothesis that GA suppression could be associated with an increased
      risk of acute gastroenteritis and pneumonia in children treated with GA
      inhibitors, we conducted a multicenter, prospective study. METHODS: The study was
      performed by expert pediatric gastroenterologists from 4 pediatric
      gastroenterology centers. Children (aged 4-36 months) consecutively referred for
      common GERD-related symptoms (for example, regurgitation and vomiting, feeding
      problems, effortless vomiting, choking), from December 2003 to March 2004, were
      considered eligible for the study. Exclusion criteria were a history of GA
      inhibitors therapy in the previous 4 months, Helicobacter pylori infection,
      diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food
      allergy, congenital motility gastrointestinal disorders, neuromuscular diseases,
      or malnutrition. Control subjects were recruited from healthy children visiting
      the centers for routine examinations. The diagnosis of GERD was confirmed in all
      patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50
      children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the
      physicians for 2 months. All enrolled children were evaluated during a 4-month
      follow-up. The end point was the number of patients presenting with acute
      gastroenteritis or community-acquired pneumonia during a 4-month follow-up study
      period. RESULTS: We obtained data in 186 subjects: 95 healthy controls and 91 GA
      inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were
      comparable for age, gender, weight, length, and incidence of acute
      gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects
      presenting with acute gastroenteritis and community-acquired pneumonia was
      significantly increased in patients treated with GA inhibitors compared with
      healthy controls during the 4-month follow-up period. In the GA inhibitor-treated
      group, the rate of subjects presenting with acute gastroenteritis and community
      acquired pneumonia was increased when comparing the 4 months before and after
      enrollment. No differences were observed between H2 blocker and PPI users in
      acute gastroenteritis and pneumonia incidence in the previous 4 months and during
      the follow-up period. On the contrary, in healthy controls, the incidence of
      acute gastroenteritis and pneumonia remained stable. CONCLUSIONS: This is the
      first prospective study performed in pediatric patients showing that the use of
      GA inhibitors was associated with an increased risk of acute gastroenteritis and
      community-acquired pneumonia in GERD-affected children. It could be interesting
      to underline that we observed an increased incidence of intestinal and
      respiratory infection in otherwise healthy children taking GA inhibitors for GERD
      treatment. On the contrary, the majority of the previous data showed that the
      patients most at risk for pneumonia were those with significant comorbid
      illnesses such as diabetes or immunodeficiency, and this points to the importance
      of GA suppression as a major risk factor for infections. In addition, this effect
      seems to be sustained even after the end of therapy. The results of our study are
      attributable to many factors, including direct inhibitory effect of GA inhibitors
      on leukocyte functions and qualitative and quantitative gastrointestinal
      microflora modification. Additional studies are necessary to investigate the
      mechanisms of the increased risk of infections in children treated with GA
      inhibitors, and prophylactic measures could be considered in preventing them.

PMID- 16651286
TI  - The safety of trivalent influenza vaccine among healthy children 6 to 24 months
      of age.
AB  - OBJECTIVE: The objective of this study was to assess the safety of routine
      trivalent influenza vaccine (TIV) administration among healthy children 6 through
      23 months of age, after the Advisory Committee on Immunization Practices
      recommendation. METHODS: The study was a retrospective case-control study of
      children receiving TIV in the first 2 seasons after the Advisory Committee on
      Immunization Practices recommendation. We assessed outcomes in the 42 days after
      vaccination in a population of 13,383 children. Each case subject was matched,
      according to age and gender, with 3 control subjects. Hazard ratios were
      calculated with conditional logistic regression analysis. RESULTS: We found no
      statistically significantly elevated hazard ratios for the first TIV dose. An
      elevated risk of pharyngitis was found for children receiving a second TIV dose.
      No elevated risk of seizure was found. CONCLUSION: These results, for a
      population of healthy children, showed no medically significant adverse events
      related to TIV among children 6 to 23 months of age.

PMID- 16651287
TI  - Intussusception after administration of the rhesus tetravalent rotavirus vaccine
      (Rotashield): the search for a pathogenic mechanism.
AB  - OBJECTIVES: The rhesus tetravalent rotavirus vaccine (RRV) was withdrawn from the
      routine program for childhood immunization in the United States because of the
      rare and unexpected occurrence of intussusception in the 2-week period after
      administration of the first dose. METHODS: To search for the pathogenesis of this
      association, we compared the pathology of surgical specimens from infants who had
      surgical reduction of their intussusceptions within 2 weeks of receiving the
      vaccine (case patients; n = 8) with the pathology of specimens from children who
      had surgery > 2 weeks after immunization (n = 6) or who had never been immunized
      (n = 26). Tissue was examined for evidence of the vaccine strain of rotavirus by
      reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization,
      and immunohistochemical staining. RESULTS: RRV was identified by RT-PCR in tissue
      samples from 7 of the 8 case patients and in 2 of the 6 children who received the
      vaccine at a more distant time (29 and 58 days before surgery), but it was not
      identified in samples from any of the nonvaccinated children. No evidence of
      rotavirus tissue involvement was detected in any of the children by in situ
      hybridization or immunohistochemical staining. Pathologic evidence (for example,
      inclusion bodies, smudge cells) of adenovirus infection was present in 35% of the
      37 specimens examined by routine staining and immunohistochemistry. CONCLUSIONS:
      The fact that RRV was detected by RT-PCR but not by either of the other assays
      could be explained by RRV being present in the lumen of the gut but not in the
      tissues of appendix, ileum, or Peyer's patches. The Peyer's patches were not
      hyperplastic, and we could not establish the pathogenic mechanism for this
      association.

PMID- 16651288
TI  - Varicella-related hospitalization and emergency department visit rates, before
      and after introduction of varicella vaccine, among white and black children in
      Hamilton County, Ohio.
AB  - OBJECTIVE: The American Academy of Pediatrics recommended routine use of
      varicella vaccine in pediatric practice in 1995. We examined the impact of
      varicella immunization on population-based rates of pediatric varicella-related
      hospitalizations and emergency department (ED) visits in the years before and
      after introduction of varicella vaccine. STUDY DESIGN: Discharge data for
      hospitalizations and ED encounters from 1990 through 2003 were queried for
      patients <20 years of age with varicella International Classification of
      Diseases, Ninth Revision, Clinical Modification codes (052.0-052.9) in any
      diagnostic position. Addresses were geocoded for identification of Hamilton
      County, Ohio, residents. Rates were calculated according to year, age, and race,
      with census estimates. RESULTS: During the 14-year study period, there were 3983
      incident varicella cases; 335 patients were hospitalized and 3833 were treated
      only in the ED. The rate of varicella-related hospitalizations decreased from
      15.7 cases per 100,000 population to 5.5 cases per 100,000 population between the
      prevaccine period (1990-1995) and the postvaccine period (1996-2003); varicella
      related ED use decreased from 178.2 cases per 100,000 population to 61.2 cases
      per 100,000 population. In the prevaccine period, hospitalization and ED visit
      rates were significantly higher for black children than for white children. In
      the postvaccine period, hospitalization rates did not differ according to race
      but ED visit rates remained significantly higher for black children, compared
      with white children. CONCLUSIONS: Varicella-related hospitalization and ED visit
      rates decreased significantly for both white and black children in Hamilton
      County, Ohio, after the introduction of varicella vaccine, and the racial
      disparity found before licensure decreased after licensure.

PMID- 16651289
TI  - A multicenter case-control study on predictive factors distinguishing childhood
      leukemia from juvenile rheumatoid arthritis.
AB  - OBJECTIVE: Acute lymphocytic leukemia (ALL) often presents with musculoskeletal
      concerns such as pain or swelling, even before appearance of blasts in the
      peripheral blood. Such presentation may lead to misdiagnosis of a child with
      juvenile rheumatoid arthritis (JRA). This study was designed to identify the
      predictive factors for leukemia using basic clinical and laboratory information.
      METHODS: A retrospective chart review was performed using a simple questionnaire
      to compare the clinical and laboratory findings present during the initial visit
      to a pediatric rheumatology clinic for 277 children who were ultimately diagnosed
      with either JRA (n = 206) or ALL (n = 71). Sensitivity and specificity analysis
      of a variety of parameters, both singly and in combination, was performed to
      identify predictive value for ALL. RESULTS: The majority (75%) of children with
      ALL did not have blasts in the peripheral blood at the time of evaluation by
      pediatric rheumatologists. In children presenting with unexplained
      musculoskeletal complaints, the 3 most important factors that predicted a
      diagnosis of ALL were low white blood cell count (< 4 x 10(9)/L), low-normal
      platelet count (150-250 x 10(9)/L), and history of nighttime pain. In the
      presence of all 3, the sensitivity and specificity for a diagnosis of ALL were
      100% and 85%, respectively. Other findings, including antinuclear antibody, rash,
      and objective signs of arthritis, were not helpful in differentiating between
      these diagnoses because they occurred at similar rates in both groups.
      CONCLUSIONS: When a child develops new-onset bone-joint complaints, the presence
      of subtle complete blood count changes combined with nighttime pain should lead
      to consideration of leukemia as the underlying cause.

PMID- 16651290
TI  - The effect of instituting a prehospital-discharge newborn bilirubin screening
      program in an 18-hospital health system.
AB  - OBJECTIVE: Kernicterus is a rare but devastating condition. The prevention of
      bilirubin-induced brain injury is based on the detection of infants at risk for
      developing severe hyperbilirubinemia. In an 18-hospital health system,
      Intermountain Health Care (IHC), we initiated a program of predischarge bilirubin
      screening of all neonates and coupled this with a results assessment using a
      percentile-based nomogram. Data during 2 periods of time, before versus after
      initiating the program, were compared to assess the effect of the program on
      significant hyperbilirubinemia and rehospitalization. METHODS: We conducted a
      historic cohort study involving all neonates delivered at > or =35 weeks'
      gestation, within IHC's 18-hospital system, during 2 periods of time: March 1,
      2001, to December 31, 2002, versus January 1, 2003, to December 31, 2004. A
      bilirubin screening program, instituted in December 2002, called for a total
      serum bilirubin (TSB) or transcutaneous bilirubin measurement to be performed on
      every neonate either at the recognition of clinical jaundice or before discharge
      regardless of whether jaundice was observed. For nonjaundiced neonates, the
      nursery staff was encouraged to obtain the screening TSB at the same time they
      obtained the state-mandated newborn screen for inborn errors of metabolism.
      Bilirubin values were plotted on an hour-specific nomogram and the corresponding
      percentile was used to guide evaluation, therapy, and follow-up. This study
      compared TSB data and readmission data for a 2-year period before versus a 2-year
      period after implementing the program. RESULTS: The study involved 101272
      neonates: 48789 in period 1 and 52483 in period 2. Before the program, 1 in every
      77 neonates born at an IHC hospital had 1 or more serum bilirubin levels >20
      mg/dL. After initiating the program, the incidence fell to 1 in 142 and the
      number of neonates with a level >25 mg/dL fell from 1 in 1522 before to 1 in 4037
      after. The rate of hospital readmission with a primary diagnosis of jaundice fell
      from 0.55% in period 1 to 0.43% in period 2. CONCLUSIONS: Initiating a program of
      bilirubin screening in a multihospital health system, coupled with evaluating the
      results using a percentile-based nomogram, reduced the proportion of neonates
      with significant hyperbilirubinemia and reduced the rate of hospital readmissions
      with jaundice.

PMID- 16651291
TI  - Racial disparities in childhood asthma in the United States: evidence from the
      National Health Interview Survey, 1997 to 2003.
AB  - OBJECTIVE: To examine differences in asthma prevalence and emergency department
      (ED) visits for asthma between non-Hispanic black and white children, and factors
      that might explain those differences, in a large, nationally representative
      sample covering the period 1997 to 2003. METHODS: Bivariate and multivariate
      regression analyses (with logit and multinomial logit methods) were conducted
      with a sample consisting of all non-Hispanic black and white children (<18 years
      of age) from the 1997 to 2003 rounds of the National Health Interview Survey.
      Models included a progressively larger set of controls for factors that might
      explain racial differences in asthma prevalence and ED visits for asthma.
      RESULTS: Being black was associated with a greater likelihood of currently having
      asthma and with a greater likelihood of having gone to the ED for asthma
      treatment in the past 1 year. Elevated asthma risks for black children were
      robust after controlling for a host of child and family characteristics that
      might explain them. CONCLUSIONS: Black children are more likely to have asthma
      and to experience ED visits for asthma, compared with otherwise comparable white
      children, and these racial disparities cannot be explained by differences in
      measurable child or family characteristics. These results suggest that racial
      disparities in asthma continue to pose risks for black children, and they point
      to the need for additional research into potential explanations and remedies.

PMID- 16651292
TI  - Effectiveness of population-based newborn hearing screening in England: ages of
      interventions and profile of cases.
AB  - OBJECTIVE: The objective of this study was to determine the effectiveness in
      routine practice of the first phase of a national population-based newborn
      hearing screening and follow-up program that seeks to identify infants with
      bilateral permanent hearing loss of > or =40-dB hearing loss. METHODS: The study
      was a part of the independent evaluation of the 23 first phase sites (annual
      birth population approximately 120,000) of the national newborn hearing screening
      program in England. For each infant identified with the defined hearing loss, the
      measures of interest were degree and type of hearing loss, presence of risk
      factors, age of first audiologic assessment, age of identification of hearing
      loss, age of enrollment in an early support program, and age of hearing aid
      fitting. Data collection took place over the first 2 years of the program.
      RESULTS: Data were provided on 169 infants with permanent bilateral moderate or
      greater hearing loss identified through screening 169487 infants. Fifty-four
      percent of all cases were from an "at-risk" population. Three fourths of these
      "at-risk" infants spent > or =48 hours in the NICU. For the whole sample, the
      median age at first audiologic assessment was 5 weeks; the median age of
      identification of the hearing loss and of enrollment in early support program was
      10 weeks irrespective of the degree of hearing loss; and the median age at
      hearing aid fitting was 16 weeks. Infants with moderate hearing loss were fitted
      with hearing aids significantly later than those with severe and profound hearing
      loss. CONCLUSIONS: Properly implemented, a newborn hearing screening program
      based on whole populations and routine service provision can deliver satisfactory
      outcomes in terms of age of referral, identification, and intervention. The
      distribution of degree and type of hearing loss and proportion with risk factors
      was similar to that expected. The numbers identified were such as to suggest that
      very few cases were missed by the screening program.

PMID- 16651293
TI  - Intrauterine growth and intelligence within sibling pairs: findings from the
      Aberdeen children of the 1950s cohort.
AB  - OBJECTIVE: The objective of this study was to examine whether the established
      positive association between birth weight and childhood psychometric intelligence
      is seen within singleton sibling pairs from the same family as well as between
      nonsiblings. METHODS: We examined the association of intrauterine growth
      (measured as birth weight standardized for gender and gestational age) with
      psychometric intelligence (measured using the Moray House picture test) at 7
      years old in a birth cohort of 9792 individuals who were singleton births
      occurring in Aberdeen, Scotland, between 1950 and 1956. We further compared this
      association within siblings with that between nonsiblings in the cohort; this
      family-based analysis included 1645 sibling pairs (N = 3290 individuals).
      RESULTS: There was a positive linear association between birth weight and
      childhood psychometric intelligence at age 7 in the whole cohort, which remained
      with adjustment for a range of potential confounding factors. A one standard
      deviation increase in birth weight for gestational age z score was associated
      with a greater intelligence score in a regression model adjusting for sex, year
      of birth, paternal social class, maternal height, age, gravidity, and birth
      outside of marriage. The mean age difference between the siblings within each
      family pair was 2.2 years. In the family-based analysis there was no strong
      association between birth weight for gestation age z score and intelligence
      within sibling pairs from the same family, but there was a positive association
      between nonsiblings; the difference in these effects being unlikely to be due to
      chance. With additional adjustment for social class, maternal height, age,
      gravidity, and birth outside of marriage, the within-sibling pair effect was
      unaltered and the nonsibling effect attenuated, although an apparently robust
      positive association remained. In these adjusted analyses there was still
      evidence that the within-sibling effect differed from that between nonsiblings.
      We found no evidence that the main effects or the family-based analyses differed
      between males and females. DISCUSSION: Our family-based analyses are consistent
      with one previous large family-based study that included >2500 sibling pairs and
      found no within-sibling-pairs association between birth weight and childhood
      intelligence, but did not make a direct statistical comparison between the within
      sibling-pairs association and that between nonsiblings. In a second large study
      that included only sibling pairs of the same sex, in males there was a within
      sibling-pairs association between birth weight and childhood intelligence.
      However, for females there was no within-sibling-pairs association. The authors
      commented that this sex difference was puzzling and needed replication. Although
      we had less power than this earlier study to assess sex differences, the point
      estimates and statistical tests in our study suggested that there was no sex
      difference. CONCLUSIONS: The lack of any association within sibling pairs from
      the same family suggests that the association between birth weight and childhood
      intelligence in the general population of singletons is largely explained by
      fixed family factors that are closely matched in siblings of a similar age. These
      factors include family socioeconomic characteristics, parental education and
      intelligence, genetic factors and fixed maternal factors, such as her behaviors,
      size, and metabolic and cardiovascular health that are constant from one
      pregnancy to the next and could therefore affect her offspring growth and
      intelligence across all pregnancies.

PMID- 16651294
TI  - Neurophysiologic assessment of neonatal sleep organization: preliminary results
      of a randomized, controlled trial of skin contact with preterm infants.
AB  - BACKGROUND: Sleep is important to brain organization, but few strategies to
      promote sleep among premature infants have been tested. Behaviorally based
      measures of sleep have shown increased quiet sleep (QS) and decreased active
      sleep (AS) during skin-to-skin contact (SSC) with the mother, but these results
      have not been confirmed with objective electroencephalographic/polysomnographic
      measures of sleep organization. Important differences exist between behavioral
      and electroencephalographic/polysomnographic definitions of sleep state. METHODS:
      Data for the first 28 relatively healthy, preterm subjects of an ongoing
      randomized trial of one 2- to 3-hour session of SSC or incubator care between
      feedings are reported here. Infants were positioned prone, inclined, and nested
      in an incubator during the 2- to 3-hour pretest period, were fed, and then went
      into the test period of SSC or incubator care. Infants were left largely
      undisturbed throughout testing. A mixed-model regression analysis compared the
      test-pretest differences in outcome measures within and between groups. RESULTS:
      Results showed that arousals were significantly lower in the SSC group, compared
      with the control group, for the entire study period and for test-pretest matched
      segments of QS and AS. Rapid eye movement was significantly lower for the SSC
      group for the study period and AS segments. Indeterminate sleep was significantly
      lower for the SSC group when confounding environmental variables were included in
      the regression analysis. When 4 subjects who experienced excessive ambient light
      levels during SSC were removed from analysis, QS increased during SSC.
      CONCLUSIONS: The patterns demonstrated by the SSC group are analogous to more
      mature sleep organization. SSC may be used as an intervention to improve sleep
      organization in this population of preterm infants.

PMID- 16651295
TI  - Third ventricle enlargement among newborn infants with trisomy 21.
AB  - OBJECTIVE: Our goal was to determine whether the third ventricle is significantly
      enlarged among neonates with trisomy 21, compared with infants without clinical
      signs of trisomy 21. This enlargement might be related to hypoplasia of the
      structures surrounding the third ventricle. These structures participate in
      cognitive development, and hypoplasia in this area may be responsible for some of
      the unique cognitive abnormalities observed among children with trisomy 21.
      METHODS: Measurements of routine head sonographic scans of 57 term infants with
      trisomy 21 who were born between January 2000 and August 2005 were performed
      within 7 days after birth and were compared with measurements of head sonographic
      scans of 21 randomly selected, healthy, term infants without trisomy 21. RESULTS:
      Although the 2 groups were of similar gestational ages, infants with trisomy 21
      were generally smaller, with smaller head circumferences. Despite the smaller
      overall head circumference, both the width and length of the third ventricle were
      enlarged among the infants with trisomy 21. Vertical measurements of the lateral
      ventricles were similar for the 2 groups. CONCLUSIONS: The third ventricle is an
      important diencephalic space. In our neonatal population, we did show significant
      enlargement of both the length and width of the third ventricle among the infants
      with trisomy 21, compared with the control group of unaffected newborns. We
      suspect that the unique neuropsychological development and cognitive dysfunction
      associated with trisomy 21 and the enlargement of the third ventricle in the
      neonatal period might be related.

PMID- 16651296
TI  - Distance from home when death occurs: a population-based study of Washington
      State, 1989-2002.
AB  - OBJECTIVE: For patients who die in hospitals, the regionalization of tertiary
      health care services may be increasing the home-to-hospital distance,
      particularly for younger patients whose care is especially regionalized and for
      whom access to and use of home hospice services remains limited. The objective of
      this study was to test the hypotheses that the distance from home at the time of
      death in a hospital has increased over time and is inversely related to the age
      of the dying patient. METHODS: A population-based case series was conducted in
      Washington State of all deaths of state residents from 1989 to 2002. The main
      outcome measure was driving distance between home residence and location at the
      time of death. RESULTS: The overall mean distance from home to the hospital where
      death occurred has increased by 1% annually. Children who died in hospitals were
      much farther from home than their adult counterparts: the mean distance was 37.4
      km for neonates and 50.9 km for children who were aged 1 to 9 years, compared
      with 19.9 km for adults who were aged 60 to 79 years and 14.0 km for patients who
      were older than 79 years. Disparities of distance were even greater among
      patients who were at the 90th percentile for distance (85.6 km for neonates
      compared with 30.8 for patient who were older than 79 years). CONCLUSIONS: The
      distance between home residence and the hospital where death occurs is greatest
      for children and has increased over time. Both of these findings have
      implications for the design of local and regional pediatric end-of-life
      supportive care services.

PMID- 16651297
TI  - Context matters: a community-based study of maternal mental health, life
      stressors, social support, and children's asthma.
AB  - OBJECTIVE: Recent national survey data indicate an overall asthma prevalence of
      12.2% for children who are younger than 18 years. Previous research in clinical
      samples of children with asthma suggests that their mothers are at greater risk
      for symptoms of depression. We describe the relationship between maternal
      symptoms of depression and having a child with asthma in a community-based
      sample. METHODS: After a school-based ascertainment of asthma and asthma symptoms
      in 15 low-income, racially/ethnically diverse public elementary schools, 1149
      eligible mothers agreed to participate in a longitudinal study. Mothers either
      had a child with previously diagnosed asthma or a child with symptoms consistent
      with possible asthma or were in the randomly selected comparison group in which
      no child in the household had asthma. During the first interview, mothers
      responded to questions about their own life stressors, supports and mental
      health, and their children's health. RESULTS: In bivariate analyses of a
      community-based sample of children who share low-income neighborhoods, mothers of
      children with diagnosed or with possible undiagnosed asthma had more symptoms of
      depression than did mothers of children who have no asthma. Mothers of children
      with diagnosed or with possible undiagnosed asthma also experienced more life
      stressors than did mothers of children without asthma. Using nested linear
      regression, we estimated a model of maternal symptoms of depression. Most of the
      variation in Center for Epidemiologic Studies-Depression score was accounted for
      by life stressors and social support. There were no independent effects of either
      asthma status or asthma status-specific child health status on maternal symptoms
      of depression. CONCLUSION: Children who are under care for chronic conditions
      such as asthma live and manage their illness outside the clinical setting. Their
      social context matters, and maternal mental health is related to their children's
      physical health. Although having a child with asthma may be "just" another
      stressor in the mother's social context, complex treatment plans must be followed
      despite the many other pressures of neighborhood and family lives.

PMID- 16651298
TI  - 2005 American Heart Association (AHA) guidelines for cardiopulmonary
      resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and
      neonatal patients: pediatric basic life support.
AB  - This publication presents the 2005 American Heart Association (AHA) guidelines
      for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC)
      of the pediatric patient and the 2005 American Academy of Pediatrics/AHA
      guidelines for CPR and ECC of the neonate. The guidelines are based on the
      evidence evaluation from the 2005 International Consensus Conference on
      Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With
      Treatment Recommendations, hosted by the American Heart Association in Dallas,
      Texas, January 23-30, 2005. The "2005 AHA Guidelines for Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care" contain recommendations designed
      to improve survival from sudden cardiac arrest and acute life-threatening
      cardiopulmonary problems. The evidence evaluation process that was the basis for
      these guidelines was accomplished in collaboration with the International Liaison
      Committee on Resuscitation (ILCOR). The ILCOR process is described in more detail
      in the "International Consensus on Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care Science With Treatment Recommendations." The recommendations
      in the "2005 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care" confirm the safety and effectiveness of many approaches,
      acknowledge that other approaches may not be optimal, and recommend new
      treatments that have undergone evidence evaluation. These new recommendations do
      not imply that care involving the use of earlier guidelines is unsafe. In
      addition, it is important to note that these guidelines will not apply to all
      rescuers and all victims in all situations. The leader of a resuscitation attempt
      may need to adapt application of the guidelines to unique circumstances. The
      following are the major pediatric advanced life support changes in the 2005
      guidelines: There is further caution about the use of endotracheal tubes.
      Laryngeal mask airways are acceptable when used by experienced providers. Cuffed
      endotracheal tubes may be used in infants (except newborns) and children in in
      hospital settings provided that cuff inflation pressure is kept <20 cm H2O.
      Confirmation of tube placement requires clinical assessment and assessment of
      exhaled carbon dioxide (CO2); esophageal detector devices may be considered for
      use in children weighing >20 kg who have a perfusing rhythm. Correct placement
      must be verified when the tube is inserted, during transport, and whenever the
      patient is moved. During CPR with an advanced airway in place, rescuers will no
      longer perform "cycles" of CPR. Instead, the rescuer performing chest
      compressions will perform them continuously at a rate of 100/minute without
      pauses for ventilation. The rescuer providing ventilation will deliver 8 to 10
      breaths per minute (1 breath approximately every 6-8 seconds). Timing of 1 shock,
      CPR, and drug administration during pulseless arrest has changed and now is
      identical to that for advanced cardiac life support. Routine use of high-dose
      epinephrine is not recommended. Lidocaine is de-emphasized, but it can be used
      for treatment of ventricular fibrillation/pulseless ventricular tachycardia if
      amiodarone is not available. Induced hypothermia (32-34 degrees C for 12-24
      hours) may be considered if the child remains comatose after resuscitation.
      Indications for the use of inodilators are mentioned in the postresuscitation
      section. Termination of resuscitative efforts is discussed. It is noted that
      intact survival has been reported following prolonged resuscitation and absence
      of spontaneous circulation despite 2 doses of epinephrine. The following are the
      major neonatal resuscitation changes in the 2005 guidelines: Supplementary oxygen
      is recommended whenever positive-pressure ventilation is indicated for
      resuscitation; free-flow oxygen should be administered to infants who are
      breathing but have central cyanosis. Although the standard approach to
      resuscitation is to use 100% oxygen, it is reasonable to begin resuscitation with
      an oxygen concentration of less than 100% or to start with no supplementary
      oxygen (ie, start with room air). If the clinician begins resuscitation with room
      air, it is recommended that supplementary oxygen be available to use if there is
      no appreciable improvement within 90 seconds after birth. In situations where
      supplementary oxygen is not readily available, positive-pressure ventilation
      should be administered with room air. Current recommendations no longer advise
      routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born
      to mothers with meconium staining of amniotic fluid. Endotracheal suctioning for
      infants who are not vigorous should be performed immediately after birth. A self
      inflating bag, a flow-inflating bag, or a T-piece (a valved mechanical device
      designed to regulate pressure and limit flow) can be used to ventilate a newborn.
      An increase in heart rate is the primary sign of improved ventilation during
      resuscitation. Exhaled CO2 detection is the recommended primary technique to
      confirm correct endotracheal tube placement when a prompt increase in heart rate
      does not occur after intubation. The recommended intravenous (IV) epinephrine
      dose is 0.01 to 0.03 mg/kg per dose. Higher IV doses are not recommended, and IV
      administration is the preferred route. Although access is being obtained,
      administration of a higher dose (up to 0.1 mg/kg) through the endotracheal tube
      may be considered. It is possible to identify conditions associated with high
      mortality and poor outcome in which withholding resuscitative efforts may be
      considered reasonable, particularly when there has been the opportunity for
      parental agreement. The following guidelines must be interpreted according to
      current regional outcomes: When gestation, birth weight, or congenital anomalies
      are associated with almost certain early death and when unacceptably high
      morbidity is likely among the rare survivors, resuscitation is not indicated.
      Examples are provided in the guidelines. In conditions associated with a high
      rate of survival and acceptable morbidity, resuscitation is nearly always
      indicated. In conditions associated with uncertain prognosis in which survival is
      borderline, the morbidity rate is relatively high, and the anticipated burden to
      the child is high, parental desires concerning initiation of resuscitation should
      be supported. Infants without signs of life (no heartbeat and no respiratory
      effort) after 10 minutes of resuscitation show either a high mortality rate or
      severe neurodevelopmental disability. After 10 minutes of continuous and adequate
      resuscitative efforts, discontinuation of resuscitation may be justified if there
      are no signs of life.

PMID- 16651299
TI  - Evaluation of a learning collaborative to improve the delivery of preventive
      services by pediatric practices.
AB  - OBJECTIVE: Effective delivery of preventive services is an essential component of
      high-quality pediatric health care. However, both variation in and deviation from
      accepted guidelines have been reported. Learning collaboratives (LCs) have been
      shown to result in improvement in several aspects of pediatric care. The
      objective of this study was to determine whether pediatric practices that
      participated in a preventive services LC would improve their delivery of
      preventive services. METHODS: After conducting an initial audit of the medical
      records of twenty 2-year-olds and twenty 4-year-olds for documentation of
      preventive services on the basis of national standards, practice teams attended a
      quality improvement workshop. They were presented with evidence to support the
      value of preventive services and the results of their audits and taught quality
      improvement methods, eg, rapid cycles of change. Each team developed plans to
      improve 1 or more services. Brief audits with feedback and monthly conference
      calls were used to support practices to conduct rapid cycles of change, to
      discuss barriers and solutions, and to monitor progress. The results of final
      chart audits of twenty 2-year-olds and 4-year-olds were compared with the initial
      chart audits. A Preventive Service Score (PSS) was assigned to each practice on
      the basis of the number of services provided, and initial to final comparisons
      were made. RESULTS: Fourteen practices participated. PSSs improved for all
      practices after the LC. Mean PSS for 2-year-olds increased from 4.0 +/- 1.1 to
      4.9 +/- 1.2 and for 4-year-olds increased from 3.8 +/- 1.8 to 5.6 +/- 1.9. The
      proportions of children who received 9 of the 10 individual preventive services
      also improved significantly. CONCLUSION: LCs are a potentially effective method
      of improving the quality of care that is delivered by pediatric practices.

PMID- 16651300
TI  - Does familiarity breed acceptance? The influence of policy on physicians'
      attitudes toward newborn screening programs.
AB  - OBJECTIVE: As newborn screening (NBS) programs expand to include conditions that
      challenge traditional public health criteria, little is known about what
      influences physicians' attitudes toward screening. We examined the effect of
      state policy and perceived state policy on pediatricians' attitudes toward
      screening. METHODS: Six hundred pediatricians from the American Academy of
      Pediatrics who practiced in Wisconsin, Colorado, Florida, or Illinois were
      queried about (1) testing high-risk infants and (2) universal NBS for cystic
      fibrosis (CF), glucose-6-phosphate dehydrogenase deficiency (G6PD), and type 1
      diabetes. RESULTS: A total of 225 (41%) of 548 eligible pediatricians returned
      223 surveys with usable data. The majority were supportive of NBS for CF (n = 188
      [84%]) and G6PD (n = 130 [58%]), whereas only 25% (n = 55) supported type 1
      diabetes screening. Pediatricians who lived in states that screen for a condition
      were more likely to support screening than those who lived in states that did not
      (CF: 117 of 119 [98%] vs 71 of 89 [80%]; type 1 diabetes: 32 of 88 [36%] vs 23 of
      109 [21%]). Physicians also were more likely to support NBS when they believed
      that it was offered in their state versus when they believed that it was not (CF:
      117 of 119 [98%] vs 52 of 65 [80%]; G6PD: 28 of 32 [88%] vs 75 of 108 [69%]; type
      1 diabetes: 7 of 14 [50%] vs 25 of 102 [25%]). CONCLUSIONS: Most pediatricians
      are supportive of NBS for CF and G6PD but not type 1 diabetes. Pediatricians who
      live in states that screen or believe that their states screen are more likely to
      support screening.

PMID- 16651301
TI  - Factors that are associated with parental acceptance of human papillomavirus
      vaccines: a randomized intervention study of written information about HPV.
AB  - OBJECTIVES: Prophylactic vaccines against human papillomavirus (HPV) are expected
      to be available for public use by 2007 and likely will be targeted to
      preadolescent children. Parental acceptance of these vaccines will be critical
      for their success. The objectives of this study were (1) to determine the overall
      acceptance of HPV vaccines for preadolescent children by parents, (2) to evaluate
      the influence of written educational information about HPV on parental
      acceptability of HPV vaccines, and (3) to identify independent predictors
      associated with HPV vaccine acceptability by parents. METHODS: A randomized
      intervention study within a cross-sectional survey was conducted. Parental HPV
      vaccine acceptability was measured under 3 different hypothetical scenarios. A
      self-administered survey on the knowledge, attitudes, and beliefs about HPV and
      HPV vaccines was sent to 1600 parents of 8- to 12-year-old children. In addition
      to a baseline paragraph about HPV that was received by all study participants, a
      random half of the study participants received a detailed "HPV Information Sheet"
      outlining the epidemiology and potential clinical sequelae of HPV infection.
      Independent predictors of parental HPV vaccine acceptability were determined
      using multivariate linear regression models. RESULTS: Parents who received the
      HPV information sheet had higher mean scores on the HPV knowledge assessment tool
      than the control group. However, despite this apparent improvement in knowledge,
      there was not a statistically significant difference in HPV vaccine acceptability
      between the 2 groups. CONCLUSIONS: Providing parents with an HPV information
      sheet did seem to improve knowledge about HPV, but this increased knowledge had
      little effect on the acceptability of these vaccines by parents for their
      children. Instead, attitudes and life experiences seemed to be more important
      factors influencing HPV vaccine acceptability among parents.

PMID- 16651302
TI  - Epilepsy surgery in young children with tuberous sclerosis: results of a novel
      approach.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with medically
      refractory epilepsy and developmental delay in children and usually results from
      cortical tubers. Seizures that begin in young patients are often refractory and
      may contribute to development delay. Functional outcome is improved when seizures
      are controlled at an early age. Previous reports have shown modest benefit from
      surgical resection of single tubers/seizure foci in older children; however, many
      children with TSC develop uncontrolled seizures before age 1. To identify
      patients who might benefit from surgery and to maximize outcome, we used a novel
      surgical approach in young children that consists of invasive intracranial
      monitoring, which is typically 3-staged and often bilateral. METHODS: Of 110
      consecutive children who underwent epilepsy surgery by a single surgeon in the
      past 6 years, 25 patients (9 boys and 16 girls) had TSC. At the time of their
      first surgery at our institution, they were a median age of 4.0 years. A total of
      31 separate admissions for epilepsy surgery in these 25 patients were identified.
      Bilateral electrode placement was performed in 13 children whose seizures could
      not be lateralized definitively preoperatively, and 22 patients underwent 3-stage
      surgeries. RESULTS: At 6 months or longer after the initial resection, 21 (84%)
      children were class I, 2 (8%) children were class II, and 2 (8%) children were
      class IV. At a mean follow-up of 28 months, 17 (68%) children were class I, 6
      (24%) were class II, and 2 (8%) were class III. Four of the 5 children who
      initially were rejected as surgical candidates because of multifocality and who
      required initial bilateral electrode study are now seizure-free. CONCLUSIONS:
      This approach can help to identify both primary and secondary epileptogenic zones
      in young TSC patients with multiple tubers. Multiple or bilateral seizure foci
      are not necessarily a contraindication to surgery. Long-term follow-up will
      determine whether this approach has durable effects.

PMID- 16651303
TI  - Adverse neonatal outcomes associated with antenatal dexamethasone versus
      antenatal betamethasone.
AB  - OBJECTIVE: Antenatal dexamethasone and betamethasone may not be equally
      efficacious in the prevention of adverse neonatal outcomes. We compared the risks
      of periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH),
      retinopathy of prematurity (ROP), and neonatal death among very low birth weight
      infants who were exposed to dexamethasone, betamethasone, or neither steroid.
      METHODS: Infants (401-1500 g) in the National Institute of Child Health and Human
      Development Neonatal Research Network were studied. Multivariate logistic
      regression analyses compared the 3 groups with regard to PVL, IVH, ROP, and
      neonatal death, adjusting for network center and selected covariates. RESULTS: A
      total of 3600 infants met entry criteria. Compared with no antenatal steroids,
      there were trends for a reduced risk for PVL associated with dexamethasone and
      betamethasone but no difference in risk between dexamethasone and betamethasone.
      Dexamethasone reduced the risk for IVH and severe IVH, compared with no antenatal
      steroid exposure. Betamethasone reduced the risk for IVH, severe IVH, and
      neonatal death, compared with no antenatal steroids. Compared with betamethasone,
      dexamethasone had a statistically significant increased risk for neonatal death.
      There were trends for greater risks associated with dexamethasone compared with
      betamethasone for IVH and severe ROP. CONCLUSIONS: Betamethasone was associated
      with a reduced risk for neonatal death, with trends of decreased risk for other
      adverse neonatal outcomes, compared with dexamethasone. It may be in the best
      interest of neonates to receive betamethasone rather than dexamethasone when
      available.

PMID- 16651304
TI  - Pain assessment for pediatric patients in the emergency department.
AB  - OBJECTIVE: To examine the relationship between pediatric patient visit
      characteristics and pain score documentation in the emergency department (ED) and
      determine whether documentation of a pain score is associated with increased
      analgesic use. METHODS: A cross-sectional analysis was conducted of ED visits for
      pediatric patients from the National Hospital Ambulatory Medical Care Survey
      (1997-2000). Survey weighted regression first was used to assess the association
      between patient visit characteristics and pain score documentation. The
      regression then was repeated to determine the association between documentation
      of a pain score and analgesic use, adjusting for visit characteristics. RESULTS:
      A total of 24,707 visits were included. Only 44.5% of visits had documented pain
      scores. In the regression analysis, younger age, self-pay, visits to pediatric
      facilities, and visits that were not designated as injury related were associated
      with decreased pain score documentation. Documentation of pain score was
      associated with increased odds of an analgesic prescription and opioid
      prescription. When no pain score was documented, the odds of receiving any
      analgesic was similar to visits with pain documented as mild. CONCLUSION: ED pain
      score documentation is suboptimal in the pediatric population. Infants and
      toddlers are at particular risk for not having a pain score documented. There is
      a significant association between pain score documentation and the use of any
      analgesic, particularly opioids. Improvements in pain documentation for acutely
      ill and injured children are needed to improve pain management.

PMID- 16651305
TI  - Controlled clinical trial of dichloroacetate for treatment of congenital lactic
      acidosis in children.
AB  - OBJECTIVE: Open-label studies indicate that oral dichloroacetate (DCA) may be
      effective in treating patients with congenital lactic acidosis. We tested this
      hypothesis by conducting the first double-blind, randomized, control trial of DCA
      in this disease. METHODS: Forty-three patients who ranged in age from 0.9 to 19
      years were enrolled. All patients had persistent or intermittent hyperlactatemia,
      and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase
      deficiency, 25 patients had 1 or more defects in enzymes of the respiratory
      chain, and 7 patients had a mutation in mitochondrial DNA. Patients were
      preconditioned on placebo for 6 months and then were randomly assigned to receive
      an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours.
      The primary outcome results were (1) a Global Assessment of Treatment Efficacy,
      which incorporated tests of neuromuscular and behavioral function and quality of
      life; (2) linear growth; (3) blood lactate concentration in the fasted state and
      after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses
      and hospitalizations; and (5) safety, including tests of liver and peripheral
      nerve function. OUTCOME: There were no significant differences in Global
      Assessment of Treatment Efficacy scores, linear growth, or the frequency or
      severity of intercurrent illnesses. DCA significantly decreased the rise in blood
      lactate caused by carbohydrate feeding. Chronic DCA administration was associated
      with a fall in plasma clearance of the drug and with a rise in the urinary
      excretion of the tyrosine catabolite maleylacetone and the heme precursor delta
      aminolevulinate. CONCLUSIONS: In this highly heterogeneous population of children
      with congenital lactic acidosis, oral DCA for 6 months was well tolerated and
      blunted the postprandial increase in circulating lactate. However, it did not
      improve neurologic or other measures of clinical outcome.

PMID- 16651306
TI  - Qualitative analysis of mothers' decision-making about vaccines for infants: the
      importance of trust.
AB  - BACKGROUND: The high visibility of controversies regarding vaccination makes it
      increasingly important to understand how parents decide whether to vaccinate
      their infants. OBJECTIVE: The purpose of this research was to investigate
      decision-making about vaccinations for infants. DESIGN: We conducted qualitative,
      open-ended interviews. PARTICIPANTS: Subjects included mothers 1 to 3 days
      postpartum and again at 3 to 6 months. RESULTS: We addressed 3 topics: attitudes
      to vaccination, knowledge about vaccination, and decision-making. Mothers who
      intended to have their infants vaccinated ("vaccinators," n = 25) either agreed
      with or did not question vaccination or they accepted vaccination but had
      significant concerns. Mothers who did not intend to vaccinate ("nonvaccinators,"
      n = 8) either completely rejected vaccination or they purposely delayed
      vaccinating/chose only some vaccines. Knowledge about which vaccines are
      recommended for children was poor among both vaccinators and nonvaccinators. The
      theme of trust in the medical profession was the central concept that underpinned
      all of the themes about decision-making. Promoters of vaccination included
      trusting the pediatrician, feeling satisfied by the pediatrician's discussion
      about vaccines, not wanting to diverge from the cultural norm, and wanting to
      adhere to the social contact. Inhibitors included feeling alienated by or unable
      to trust the pediatrician, having a trusting relationship with an influential
      homeopath/naturopath or other person who did not believe in vaccinating, worry
      about permanent side effects, beliefs that vaccine-preventable diseases are not
      serious, and feeling that since other children are vaccinated their child is not
      at risk. CONCLUSION: Trust or lack of trust and a relationship with a
      pediatrician or another influential person were pivotal for decision-making of
      new mothers about vaccinating their children. Attempts to work with mothers who
      are concerned about vaccinating their infants should focus not only on providing
      facts about vaccines but also on developing trusting and positive relationships.

PMID- 16651307
TI  - Comparison of enzyme-linked immunospot assay and tuberculin skin test in healthy
      children exposed to Mycobacterium tuberculosis.
AB  - OBJECTIVE: To compare the enzyme-linked immunospot (ELISPOT) assay with the
      tuberculin skin test (TST) in children for the diagnosis of Mycobacterium
      tuberculosis infection in the Gambia. METHODS: We divided child contacts of
      sputum smear-positive tuberculosis cases into 3 age categories (<5, 5-9, and 10
      14 years) and assessed agreement between the 2 tests plus their relationship to
      prior Bacille Calmette-Guerin (BCG) vaccination. We categorized a child's level
      of M tuberculosis exposure according to where he/she slept relative to a case:
      the same room, same house, or a different house. The relationship between
      exposure and test result was assessed by multiple logistic regression. RESULTS:
      In child contacts of 287 cases, 225 (32.5%) of 693 were positive by TST and 232
      (32.3%) of 718 by ELISPOT. The overall agreement between tests was 83% and the
      discordance was not significant. Both tests responded to the M tuberculosis
      exposure gradient in each age category. The percentage of those who were TST
      positive/ELISPOT negative increased with increasing exposure. At the lowest
      exposure level, the percentage of ELISPOT-positive children who were TST negative
      was increased compared with the highest exposure level. Neither test had evidence
      of false positive results because of BCG. CONCLUSIONS: In Gambian children, the
      ELISPOT is slightly less sensitive than the TST in the diagnosis of M
      tuberculosis infection from recent exposure, and neither test is confounded by
      prior BCG vaccination. Evidence of reduced TST sensitivity in subjects with the
      lowest known recent M tuberculosis exposure suggests that, when maximal
      sensitivity is important, the 2 tests may be best used together.

PMID- 16651308
TI  - Delayed whole-body cooling to 33 or 35 degrees C and the development of impaired
      energy generation consequential to transient cerebral hypoxia-ischemia in the
      newborn piglet.
AB  - OBJECTIVES: Fundamental questions remain about the precise temperature providing
      optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if
      hypothermia delays the onset of the neurotoxic cascade and the secondary
      impairment in cerebral energy generation, the "latent phase" may be prolonged,
      thus extending the period when additional treatments may be effective. The aims
      of this study were to investigate the effects of delayed systemic cooling at
      either 33 degrees C or 35 degrees C on the following: (1) latent-phase duration,
      and (2) cerebral metabolism during secondary energy failure itself, in the 48
      hour period after transient HI. METHODS: Piglets were randomly assigned to the
      following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2)
      HI-Trectal 35 degrees C (HI-35; n = 7), and (3) HI-Trectal 33 degrees C (HI-33; n
      = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI.
      Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of
      cooling on secondary energy failure severity (indexed by the nucleotide
      triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic
      phosphate [PCr/Pi] ratios) was assessed. RESULTS: Compared with HI-n, HI-35 and
      HI-33 had a longer NTP/EPP latent phase and during the entire study duration had
      higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and
      the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the
      hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled
      groups, but this advantage was not maintained after rewarming. Compared with HI
      n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS: Whole-body
      hypothermia for 24 hours at either 35 or 33 degrees C, commenced 2 hours after
      resuscitation, prolonged the NTP/EPP latent phase and reduced the overall
      secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the
      temperature from 35 to 33 degrees C neither increased mean PCr/Pi and NTP/EPP nor
      further lengthened the latent phase.

PMID- 16651309
TI  - Impaired flow-mediated vasodilation, carotid artery intima-media thickening, and
      elevated endothelial plasma markers in obese children: the impact of
      cardiovascular risk factors.
AB  - OBJECTIVES: Childhood obesity contributes to the development of adult obesity and
      subsequent cardiovascular disease. The present study aimed to assess vascular
      status (flow-mediated vasodilation [FMD], intima-media thickness [IMT]) and to
      analyze plasma surrogate endothelial markers (von Willebrand factor [vWf], E
      selectin, and thrombomodulin) in obese children as compared with controls.
      Associations between early morphologic and functional vascular changes, surrogate
      soluble markers of early atherosclerosis, and the cardiovascular risk profile
      were determined. METHODS: We examined 32 obese children versus 20 control
      subjects. All of the children underwent identical screening, comprehensive risk
      factor assessment, and measurements of E-selectin, vWf, thrombomodulin, FMD, and
      IMT. RESULTS: Compared with controls, obese children demonstrated significantly
      impaired FMD and increased IMT. Concentrations of soluble E-selectin and
      thrombomodulin were significantly elevated in obese children, whereas vWf showed
      no significant differences between obese children and controls. FMD, IMT, E
      selectin, and thrombomodulin were significantly associated with various risk
      factors, including the extent of obesity, arterial hypertension, fibrinogen, C
      reactive protein, and low physical fitness. CONCLUSIONS: The present study
      documented increased IMT, impaired endothelial function, and elevated plasma
      markers of endothelial activation and injury in obese children. Morbid obesity,
      arterial hypertension, subclinical inflammation, and low physical fitness formed
      a risk profile associated with the risk of early atherosclerosis in these
      children. Sonographic assessment of vascular status and the estimation of soluble
      endothelial plasma markers, combined with comprehensive risk factor screening,
      may form a rationale to identify high-risk children susceptible to early
      atherosclerotic disease and to monitor vascular changes during follow-up studies
      and therapeutic measures.

PMID- 16651310
TI  - Do bullied children get ill, or do ill children get bullied? A prospective cohort
      study on the relationship between bullying and health-related symptoms.
AB  - OBJECTIVES: A number of studies have shown that victimization from bullying
      behavior is associated with substantial adverse effects on physical and
      psychological health, but it is unclear which comes first, the victimization or
      the health-related symptoms. In our present study, we investigated whether
      victimization precedes psychosomatic and psychosocial symptoms or whether these
      symptoms precede victimization. DESIGN: Six-month cohort study with baseline
      measurements taken in the fall of 1999 and follow-up measurements in the spring
      of 2000. SETTING: Eighteen elementary schools in the Netherlands. PARTICIPANTS:
      The study included 1118 children aged 9 to 11 years, who participated by filling
      out a questionnaire on both occasions of data collection. OUTCOME MEASURES: A
      self-administered questionnaire measured victimization from bullying, as well as
      a wide variety of psychosocial and psychosomatic symptoms, including depression,
      anxiety, bedwetting, headaches, sleeping problems, abdominal pain, poor appetite,
      and feelings of tension or tiredness. RESULTS: Victims of bullying had
      significantly higher chances of developing new psychosomatic and psychosocial
      problems compared with children who were not bullied. In contrast, some
      psychosocial, but not physical, health symptoms preceded bullying victimization.
      Children with depressive symptoms had a significantly higher chance of being
      newly victimized, as did children with anxiety. CONCLUSIONS: Many psychosomatic
      and psychosocial health problems follow an episode of bullying victimization.
      These findings stress the importance for doctors and health practitioners to
      establish whether bullying plays a contributing role in the etiology of such
      symptoms. Furthermore, our results indicate that children with depressive
      symptoms and anxiety are at increased risk of being victimized. Because
      victimization could have an adverse effect on children's attempts to cope with
      depression or anxiety, it is important to consider teaching these children skills
      that could make them less vulnerable to bullying behavior.

PMID- 16651311
TI  - Psychological differences between children with and without soiling problems.
AB  - OBJECTIVES: Previous studies, based on clinic samples, report that childhood
      soiling is associated with behavior problems and reduced self-esteem. This
      population-based study investigates the prevalence of psychological problems
      associated with childhood soiling. METHODS: A total of 8242 children aged 7-8
      years born to mothers in the United Kingdom-based Avon Longitudinal Study of
      Parents and Children were studied. Parents completed postal questionnaires
      assessing common childhood emotional and behavioral problems, and children were
      asked questions at a research clinic concerning their behavior, friendships,
      bullying, and self-esteem. The rate of psychological problems was compared in
      children who soil frequently (once a week or more), those who soil occasionally
      (less than once a week), and those with no soiling problems (controls). Analyses
      were adjusted for developmental delay, gender, sociodemographic background, and
      stressful life events. RESULTS: Children who soil were reported by their parents
      to have significantly more emotional and behavioral problems compared with
      children who do not soil. Children who soil frequently had significantly more
      problems than those who soil occasionally. The rate of attention and activity
      problems, obsessions and compulsions, and oppositional behavior was particularly
      high in frequently soiling children. Children with soiling problems reported
      significantly higher rates of involvement in overt bullying (as both perpetrator
      and victim) and antisocial activities compared with controls. CONCLUSIONS: The
      current study finds significantly higher rates of behavior and emotional
      problems, bullying, and antisocial activities in children who soil compared with
      those who do not soil. Children who soil frequently are more likely to have these
      problems than those who soil occasionally.

PMID- 16651312
TI  - Verbal abuse by the teacher and child adjustment from kindergarten through grade
      6.
AB  - OBJECTIVES: Many adults mention past incidences of verbal abuse by the teacher as
      the most overwhelming negative experience in their lives. The present study
      examined (1) the course and stability of verbal abuse by the teacher from
      kindergarten through grade 4 and (2) the link between verbal abuse by the teacher
      and children's behavioral, emotional, and academic adjustment. DESIGN:
      Participants were 399 children (177 girls) who were assessed yearly over a period
      of 7 years, starting in kindergarten. Verbal abuse by the teacher, as well as
      acceptance versus rejection by the peer group from kindergarten through grade 4,
      were assessed through peer nomination. Child adjustment from kindergarten through
      grade 4 (antisocial behavior, attention problems, anxiety) was evaluated by the
      teacher. Child adjustment in early adolescence (delinquent behavior, depressive
      feelings, academic performance) was assessed by teacher evaluations and self
      reports. RESULTS: The vast majority of children (approximately 85%) have almost 0
      risk of becoming a target of verbal abuse by the teacher over the course of
      elementary school. However, a small minority of children (15%) seems to be at
      relatively high risk of verbal abuse by the teacher in kindergarten, and this
      risk increases even further over the course of elementary school. Boys, as well
      as children with high levels of early antisocial behavior and attention problems
      in kindergarten, are at high risk of verbal abuse by the teacher during
      elementary school. In turn, verbal abuse by the teacher is significantly related
      to subsequent delinquent behavior and academic difficulties in early adolescence,
      although this effect depends on child characteristics. CONCLUSIONS: Verbal abuse
      by the teacher seems to be a highly stable phenomenon for at-risk children.
      Children who are relatively well adjusted are at low risk of becoming the target
      of verbal abuse by the teacher. If they do, however, these children are the most
      vulnerable to subsequent developmental difficulties.

PMID- 16651313
TI  - Differences in infant and parent behaviors during routine bed sharing compared
      with cot sleeping in the home setting.
AB  - OBJECTIVES: To observe the behavior of infants sleeping in the natural physical
      environment of home, comparing the 2 different sleep practices of bed sharing and
      cot sleeping quantifying to factors that have been identified as potential risks
      or benefits. METHODS: Forty routine bed-sharing infants, aged 5-27 weeks were
      matched for age and season of study with 40 routine cot-sleeping infants.
      Overnight video and physiologic data of bed-share infants and cot-sleep infants
      were recorded in the infants' own homes. Sleep time, sleep position, movements,
      feeding, blanket height, parental checks, and time out of the bed or cot were
      logged. RESULTS: The total sleep time was similar in both groups (bed-sharing
      median: 8.6 hours; cot-sleeping median: 8.2 hours). Bed-sharing infants spent
      most time in the side position (median: 5.7 hours, 66% of sleep time) and most
      commonly woke at the end of sleep in this position, whereas cot-sleeping infants
      most commonly slept supine (median: 7.5 hours, 100%) and woke at the end of sleep
      in the supine position. Prone sleep was uncommon in both groups. Head covering
      above the eyes occurred in 22 bed-sharing infants and 1 cot-sleeping infant. Five
      of these bed-sharing infants were head covered at final waking time, but the cot
      sleeping infant was not. Bed-sharing parents looked at or touched their infant
      more often (median: 11 vs 4 times per night) but did not always fully wake to do
      so. Movement episodes were shorter in the bed-sharing group as was total movement
      time (37 vs 50 minutes respectively), whereas feeding was 3.7 times more frequent
      in the bed-sharing group than the cot-sleeping group. CONCLUSIONS: Bed-share
      infants without known risk factors for sudden infant death syndrome (SIDS)
      experience increased maternal touching and looking, increased breastfeeding, and
      faster and more frequent maternal responses. This high level of interaction is
      unlikely to occur if maternal arousal is impaired, for example, by alcohol or
      overtiredness. Increased head covering and side sleep position occur during bed
      sharing, but whether these factors increase the risk of SIDS, as they do in cot
      sleeping, requires further investigation.

PMID- 16651314
TI  - The role of early maternal responsiveness in supporting school-aged cognitive
      development for children who vary in birth status.
AB  - OBJECTIVES: To examine the relation between the pattern of maternal
      responsiveness that children experienced in the infancy, preschool, and school
      age periods and growth in cognitive skills across 3-10 years of age and determine
      whether the relation differs by birth status. METHODS: In 1990-1992, 360 children
      varying in birth status (very low birthweight [VLBW]; demographically matched
      controls) were recruited to examine parenting and birth status influences on
      development. This report includes children with observations of parenting at 6,
      12, and 24 months and 3, 4, 6, 8, and 10 years and cognitive skills evaluated at
      3, 4, 6, 8, and 10 years of age (71% of original cohort). RESULTS: Four groups of
      mothers varying in the pattern of responsiveness displayed across the infancy and
      the preschool period were found. When controlling for school-age parenting and
      economic status, children parented with higher levels of responsiveness across
      both developmental periods, irrespective of birth status, showed higher levels in
      development than those who experienced responsiveness in only 1 development
      period or minimal responsiveness. Greater benefit was found for consistency in
      responsiveness for children born VLBW with less, versus more, severe neonatal
      complications. Inspection of the means showed that higher risk birth status
      combined with minimal responsiveness resulted in cognitive scores, on average, 14
      points lower than when parented with consistently higher responsiveness.
      CONCLUSIONS: Cognitive development for children born at VLBW, particularly those
      with less severe complications, are supported by consistently responsive
      parenting across early childhood in similar ways to those born at term. This
      effect persisted through 10 years of age even after school-age parenting and
      economic level. These findings have important implications for the timing (across
      early childhood) and content (responsive interactive behaviors) of early
      intervention to enhance the outcomes for children born at VLBW.

PMID- 16651315
TI  - The changing face of race: risk factors for neonatal hyperbilirubinemia.
AB  - OBJECTIVES: Race is a predictor of health outcomes and risk for some clinical
      conditions, for example, mother's race predicts risk for hyperbilirubinemia in
      newborns, with blacks at lowest risk. Little is known about the correlation of
      race as recorded in medical records with self-reported race. Also, use of
      maternal race to predict newborn risk for hyperbilirubinemia has not been tested
      for multiracial mothers and newborns. We sought to examine how maternal race
      documented in medical records correlates with self-reported race and to examine
      the correlation between mothers' and newborns' race in the context of risk for
      neonatal hyperbilirubinemia, focusing on multiracial mothers and newborns.
      DESIGN: A cohort study with 3021 newborns at > or =35 weeks gestation discharged
      from normal nursery between January 2001 and October 2002 with a telephone survey
      of their mothers within 6 months of birth. SETTING: The study was conducted in
      the Neonatology Department of Henry Ford Hospital. PATIENTS: There were 1773
      mothers (58%) with incorrect telephone numbers. Of 1248 mothers contacted, 866
      (69%) completed the interview. OUTCOME MEASURES: We measured mother's race in
      hospital database and mother's reported race for herself, her newborn, and the
      father, allowing < or =5 responses for each. RESULTS: Of mothers documented in
      the medical record as white, 64% self-reported as white. Among mothers recorded
      as black, 70% self-reported as black. Mothers identified 93 newborns as > or =2
      races with primary race matching both parents for 41%, father for 25%, mother for
      23%, and neither parent for 11%. Of 70 newborns whose parents were not the same
      race, mothers identified 45 (64%) as > or =2 races. CONCLUSIONS: There is
      incomplete overlap between racial identification in medical records versus self
      report. Given 1 choice, mothers of multiracial infants overselect black in their
      newborns' ancestry. Because black race is the lowest risk category for neonatal
      hyperbilirubinemia, this may lead to underestimating their risk.

PMID- 16651316
TI  - Prolonged indomethacin exposure is associated with decreased white matter injury
      detected with magnetic resonance imaging in premature newborns at 24 to 28 weeks'
      gestation at birth.
AB  - OBJECTIVES: Newborns delivered before 28 weeks' gestation commonly have white
      matter lesions on MRI that are associated with adverse neurodevelopmental
      outcomes. Our objective was to determine the risk factors for MRI-detectable
      white matter injury in infants delivered before 28 weeks' gestation who were
      treated with prophylactic indomethacin. METHODS: This was a prospective cohort
      study conducted at the intensive care nursery at University of California San
      Francisco Children's Hospital. Patients included 57 premature newborns between 24
      and 27 (+6 days) weeks' gestation at birth (October 1998 to October 2004). We
      identified perinatal and neonatal risk factors associated with moderate-severe
      "white matter injuries" (T1 signal abnormalities >2 mm or >3 areas of T1
      abnormality) and moderate-severe "brain abnormality" (moderate-severe white
      matter injuries, any degree of ventriculomegaly, or severe intraventricular
      hemorrhage) on MRI. Infants were studied with MRI at 31.1 weeks' postmenstrual
      age (median). RESULTS: Moderate-severe white matter injuries were detected in 12
      (21%) of 53 preterm newborns, and 20 (35%) of 57 had moderate-severe brain
      abnormality. Prolonged indomethacin exposure was the only risk factor
      independently associated with a lower risk of white matter injury or brain
      abnormality, even when adjusting for the presence of a hemodynamically
      significant PDA, gestational age at birth, prenatal betamethasone, systemic
      infection, and days of mechanical ventilation. CONCLUSIONS: In this observational
      study, a longer duration of indomethacin exposure was associated with less white
      matter injury in infants delivered before 28 weeks' gestation. A randomized trial
      of prolonged indomethacin treatment is needed to determine whether indomethacin
      can decrease white matter injury and neurodevelopmental abnormalities.

PMID- 16651317
TI  - Mortality and morbidities among very premature infants admitted after hours in an
      Australian neonatal intensive care unit network.
AB  - OBJECTIVES: To assess risk-adjusted early (within 7 days) mortality and major
      morbidities of newborn infants at < 32 weeks' gestation who are admitted after
      office hours to a regional Australian network of NICUs where statewide caseload
      is coordinated and staffed by on-floor registrars working in shift rosters. We
      hypothesize that adverse sequelae are increased in these infants. DESIGNS: We
      conducted a database review of the records of infants (n = 8654) at < 32 weeks'
      gestation admitted to a network of 10 tertiary NICUs in New South Wales and the
      Australian Capital Territory from 1992 to 2002. Multivariate logistic regression
      analysis was performed to adjust for case-mix and significant baseline
      characteristics. OUTCOMES: Sixty-five percent of infants were admitted to the
      NICUs after hours. These infants did not have an increase in early neonatal
      mortality or major neonatal sequelae compared with their office-hours
      counterparts. Admissions during late night hours after midnight or fatigue risk
      periods before the end of a medical 12-hour shift were not associated with higher
      early mortality. Risk factors significantly predictive of early neonatal death
      were lack of antenatal steroid treatment, Apgar score < 7 at 5 minutes, male
      gender, gestation age, and being small for gestation. CONCLUSIONS: Current
      staffing levels, specialization, and networking are associated with lower
      circadian variation in adverse outcomes and after-hours admission to this NICU
      network and have no significant impact on early neonatal mortality and morbidity.

PMID- 16651318
TI  - Cost-effectiveness of neonatal extracorporeal membrane oxygenation based on 7
      year results from the United Kingdom Collaborative ECMO Trial.
AB  - OBJECTIVE: To assess the long-term cost-effectiveness of extracorporeal membrane
      oxygenation (ECMO) for mature newborn infants with severe respiratory failure.
      METHODS: A prospective economic evaluation was conducted alongside a pragmatic
      randomized, controlled trial in which 185 infants were randomly allocated to ECMO
      (n = 93) or conventional management (n = 92) and then followed up to 7 years of
      age. Information about their use of health services during the follow-up period
      was combined with unit costs (pound sterling, 2002-2003 prices) to obtain a net
      cost per child. The cost-effectiveness of neonatal ECMO was expressed in terms of
      incremental cost per additional life year gained and incremental cost per
      additional disability-free life year gained. The nonparametric bootstrap method
      was used to present cost-effectiveness acceptability curves and net benefit
      statistics at alternative willingness-to-pay thresholds held by decision-makers
      for an additional life year and for an additional disability-free life year.
      RESULTS: Over 7 years, neonatal ECMO was effective at reducing known death or
      severe disability. Mean health service costs during the first 7 years of life
      were 30,270 pound sterling in the ECMO group and 10,229 pound sterling in the
      conventional management group, generating a mean cost difference of 20,041 pound
      sterling that was statistically significant. The incremental cost per life year
      gained was estimated at 13,385 pound sterling. The incremental cost per
      disability-free life year gained was estimated at 23,566 pound sterling. At the
      notional willingness-to-pay threshold of 30,000 pound sterling for an additional
      life year, the probability that neonatal ECMO is cost-effective at 7 years was
      estimated at 0.98. This translated into a mean net benefit of 24,362 pound
      sterling for each adoption of neonatal ECMO rather than conventional management.
      CONCLUSIONS: This study provides rigorous evidence of the cost-effectiveness of
      neonatal ECMO during childhood.

PMID- 16651319
TI  - Economic analysis of prevaccination serotesting compared with presumptive
      immunization for polio, diphtheria, and tetanus in internationally adopted and
      immigrant infants.
AB  - BACKGROUND: No consensus exists about whether to conduct prevaccination
      serotesting or to presumptively vaccinate internationally adopted and immigrant
      infants with inactivated polio (IPV) and diphtheria-tetanus-acellular pertussis
      (DTaP) immunizations. OBJECTIVE: To study the clinical and economic outcomes from
      a societal perspective of prevaccination serotesting in a hypothetical 12-month
      old internationally adopted or immigrant infant. DESIGN AND METHODS: A decision
      analysis model was developed comparing presumptive vaccination with IPV versus
      serotesting for poliovirus type 1, 2, and 3 antibodies followed by vaccination in
      unprotected patients. A similar decision analysis model was developed comparing
      presumptive vaccination with DTaP versus serotesting for diphtheria and tetanus
      toxoid antibodies. The main outcome measures were cost per patient protected from
      polio, diphtheria, and tetanus. RESULTS: Compared with presumptive immunization,
      prevaccination serotesting for polio increases the cost per patient from $57 to
      $62 and decreases the percentage of patients protected against polio from 95.3%
      to 94.0%. Serotesting for diphtheria and tetanus increases the cost per patient
      from $62 to $119 and increases the percentage of patients protected against both
      diphtheria and tetanus from 91.5% to 92.3%. Presumptive immunization with DTaP
      costs less and is more clinically effective than serotesting if >80% of patients
      do not complete the full vaccine series or if antibody seroprevalence to both
      diphtheria and tetanus is <51%. CONCLUSIONS: Presumptive immunization for polio
      improves outcomes and saves costs compared with prevaccination serotesting in
      internationally adopted and immigrant infants. The results for DTaP are less
      definitive, although immunization is the preferred strategy in populations with
      poor vaccine compliance or low seroprevalence of antibodies to diphtheria and
      tetanus.

PMID- 16651320
TI  - Predictors of fatality in postdiarrheal hemolytic uremic syndrome.
AB  - OBJECTIVES: Describe the cause of deaths among patients with postdiarrheal
      hemolytic uremic syndrome (HUS) and identify predictors of death at the time of
      hospital admission. METHODS: Case-control study of 17 deaths among patients with
      HUS identified from the Intermountain HUS Patient Registry (1970-2003) compared
      against all nonfatal cases. RESULTS: Of the 17 total deaths, 15 died during the
      acute phase of disease. Two died because treatment was withdrawn based on their
      preexisting conditions, and 1 died because of iatrogenic cardiac tamponade; they
      were excluded from analysis. Brain involvement was the most common cause of death
      (8 of 12); congestive heart failure, pulmonary hemorrhage, and hyperkalemia were
      infrequent causes. Presence of prodromal lethargy, oligoanuria, or seizures and
      white blood cell count (WBC) >20 x 10(9)/L or hematocrit >23% on admission were
      predictive of death. In multivariate analysis, elevated WBC and elevated
      hematocrit were independent predictors. The combination of prodromal dehydration,
      oliguria, and lethargy and admission WBC values >20 x 10(9)/L and hematocrit >23%
      appeared in 7 of the 12 acute-phase deaths. CONCLUSIONS: Diarrheal HUS patients
      presenting with oligoanuria, dehydration, WBC >20 x 10(9)/L, and hematocrit >23%
      are at substantial risk for fatal hemolytic uremic syndrome. Such individuals
      should be referred to pediatric tertiary care centers.

PMID- 16651321
TI  - Clinical value of autoantibodies against C1q in children with glomerulonephritis.
AB  - OBJECTIVE: Autoantibodies against C1q (anti-C1q) have been found in a number of
      autoimmune and renal diseases. They are best described in adult patients with
      systemic lupus erythematosus, where a strong correlation between the occurrence
      of anti-C1q and severe lupus nephritis (LN) has been observed. However, the role
      of anti-C1q in children with systemic lupus erythematosus has not yet been
      determined. Furthermore, the clinical importance of anti-C1q in other forms of
      glomerulonephritis remains to be elucidated. The aim of this study was to
      investigate anti-C1q in children with different forms of glomerulonephritis
      including LN. METHODS: We prospectively investigated 112 children with different
      forms of newly diagnosed glomerulonephritis for the presence of anti-C1q by an
      enzyme-linked immunosorbent assay and compared them with healthy controls.
      Associations between anti-C1q and disease manifestations at the time of the
      measurements and during follow-up were investigated. RESULTS: Twenty-one of 112
      patients were positive for anti-C1q compared with 0 of 40 healthy controls. Anti
      C1q was associated with activity in LN and with disease severity in patients with
      acute poststreptococcal glomerulonephritis (APSGN). In LN, 7 of 12 patients were
      found to be anti-C1q positive. Six of these 7 had active disease at the time of
      the serum sampling compared with 1 of 5 of the anti-C1q-negative children. In
      children with APSGN, 8 of 24 were positive for anti-C1q. Anti-C1q-positive APSGN
      patients had significantly higher proteinuria and more often hypertension than
      those without anti-C1q. All 4 patients in which APSGN did not resolve
      spontaneously were anti-C1q positive. CONCLUSIONS: Anti-C1q is associated with
      active LN in children. In addition, children with anti-C1q-positive APSGN have
      more severe disease than those who are anti-C1q negative. These data suggest
      APSGN is another disease in which anti-C1q has a pathogenic role.

PMID- 16651322
TI  - Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome.
AB  - OBJECTIVES: We sought to verify the association between maternal intrahepatic
      cholestasis of pregnancy (ICP) and neonatal respiratory distress syndrome (RDS)
      and to determine how bile acids levels alter the risk of developing neonatal RDS.
      METHODS: We extracted data from our divisional database about all of the newborns
      born during the years 2000-2004. We compared 77 neonates born from pregnancies
      complicated by ICP with 427 neonates in the same range of gestational age born
      from noncomplicated pregnancies. We studied maternal bile acids levels
      immediately before delivery in mothers with ICP and measured bile acid levels
      during the first 24 hours of life in their newborns. RESULTS: The incidence of
      RDS in newborns from cholestatic pregnancies was twice that the reference
      population (28.6% vs 14%). The multivariate analysis showed that the risk of RDS
      in these newborns was approximately 2.5 times higher than in control infants.
      Within the ICP group, maternal and neonatal bile acid levels of infants affected
      by RDS were not significantly higher than those of healthy infants. The
      multivariate analysis showed that a low gestational age was the most important
      risk factor, but the probability of respiratory distress syndrome also increased
      by 2 per thousand for every additional micromole of the interaction term
      "neonatal by maternal bile acids level." CONCLUSIONS: Maternal ICP is
      significantly associated with the occurrence of RDS in the newborn. We
      hypothesize that bile acids can produce surfactant depletion in the alveoli
      reverting the reaction of phospholipase A2. This hypothesis could potentially be
      confirmed by bronchoalveolar lavage study.

PMID- 16651323
TI  - Venous thrombosis associated with staphylococcal osteomyelitis in children.
AB  - BACKGROUND: Venous thrombosis (VT) in children with Staphylococcus aureus
      osteomyelitis occurs rarely. We describe clinical features of infections and
      molecular characterization of isolates of children at Texas Children's Hospital
      with S aureus osteomyelitis and VT. METHODS: We reviewed records and imaging
      studies (chest radiographs, ultrasound, computed tomography, and MRI) of 9
      patients at Texas Children's Hospital with acute S aureus osteomyelitis and new
      onset VT between August 1999 and December 2004. Isolates were fingerprinted by
      pulsed-field gel electrophoresis and tested for the presence of genes encoding
      selective virulence factors. RESULTS: The mean age of the patients was 10.6
      years. All 9 of the patients had osteomyelitis with sites of infection adjacent
      to the VT. The femoral and popliteal veins were most commonly affected. Two
      patients had VTs develop on the same side in which a central line had been in
      place. Four patients had chest radiographs consistent with septic emboli;
      inferior vena cava filters were placed in 3. Evaluation for hypercoagulable state
      revealed 3 patients with lupus anticoagulant, 1 with anticardiolipin IgG
      antibody, and 5 with no defect. Most laboratory abnormalities had resolved at
      follow-up. Seven patients had infections caused by methicillin-resistant S aureus
      belonging to the same clonal group (USA300); all were community acquired. Seven
      isolates carried the Panton-Valentine leukocidin (luk-S-PV and luk-F-PV) genes.
      CONCLUSIONS: The predominant community-acquired, methicillin-resistant S aureus
      clone in Houston, Texas, (USA300) may have a unique propensity to cause VT in
      association with osteomyelitis. Management of the venous thrombosis in this
      setting may be complicated by the rapid evolution of septic emboli.

PMID- 16651324
TI  - Changing incidence of Candida bloodstream infections among NICU patients in the
      United States: 1995-2004.
AB  - OBJECTIVES: Recent reports suggest that candidemia caused by fluconazole
      resistant strains is increasing in certain adult populations. We evaluated the
      annual incidence of neonatal candidemia and the frequency of disease caused by
      different species of Candida among neonates in the United States. PATIENTS: The
      study included neonates admitted to 128 NICUs participating in the National
      Nosocomial Infections Surveillance system from January 1, 1995, to December 31,
      2004 (study period). METHODS: Reports of bloodstream infection (BSI) with Candida
      spp.; Candida BSIs, patient admissions, patient-days, and central venous catheter
      days were pooled by birth weight category. The number of Candida BSIs per 100
      patients (attack rate) and per 1000 patient-days (incidence density) was
      determined. Both overall and species-specific rates were calculated; data were
      pooled over time to determine the differences by birth weight category and by
      year to determine trends over time. RESULTS: From the 130,523 patients admitted
      to NICUs during the study period, there were 1997 Candida spp. BSIs reported.
      Overall, 1472 occurred in the <1000-g birth weight group. Candida albicans BSIs
      were most common, followed by Candida parapsilosis, Candida tropicalis, Candida
      lusitaniae, Candida glabrata, and only 3 Candida krusei. Among neonates <1000 g,
      incidence per 1000 patient-days decreased from 3.51 during 1995-1999 to 2.68
      during 2000-2004 but remained stable among heavier neonates. No increase in
      infections by species that tend to demonstrate resistance to fluconazole (C
      glabrata or C krusei) was observed. CONCLUSIONS: Although Candida BSI is a serous
      problem among neonates <1000 g, incidence has declined over the past decade, and
      disease with species commonly resistant to azoles was extremely rare.

PMID- 16651325
TI  - Early vancomycin therapy and adverse outcomes in children with pneumococcal
      meningitis.
AB  - BACKGROUND: Experts recommend that children with suspected pneumococcal
      meningitis should empirically receive combination therapy with vancomycin plus
      either ceftriaxone or cefotaxime. The relationship between timing of the first
      dose of vancomycin relative to other antibiotics and outcome in these children,
      however, has not been addressed. METHODS: Medical records of children with
      pneumococcal meningitis at a single institution from 1991-2001 were
      retrospectively reviewed. Vancomycin start time was defined as the number of
      hours from initiation of cefotaxime or ceftriaxone therapy until the
      administration of vancomycin therapy. Outcome variables were death, sensorineural
      hearing loss, and other neurologic deficits at discharge. Associations between
      independent variables and outcome variables were assessed in univariate and
      multiple logistic regression analyses. RESULTS: Of 114 subjects, 109 received
      empiric vancomycin therapy in combination with cefotaxime or ceftriaxone. Ten
      subjects (9%) died, whereas 37 (55%) of 67 survivors who underwent audiometry had
      documented hearing loss, and 14 (13%) of 104 survivors were discharged with other
      neurologic deficits. Subjects with hearing loss had a significantly shorter
      median vancomycin start time than did those with normal hearing (<1 vs 4 hours).
      Vancomycin start time was not significantly associated with death or other
      neurologic deficits in univariate or multivariate analyses. Multiple logistic
      regression revealed that hearing loss was independently associated with
      vancomycin start time <2 hours, blood leukocyte count <15000/microL, and
      cerebrospinal fluid glucose concentration <30 mg/dL. CONCLUSIONS: Early empiric
      vancomycin therapy was not clinically beneficial in children with pneumococcal
      meningitis but was associated with a substantially increased risk of hearing
      loss. It may be prudent to consider delaying the first dose of vancomycin therapy
      until > or =2 hours after the first dose of parenteral cephalosporin in children
      beginning therapy for suspected or confirmed pneumococcal meningitis.

PMID- 16651326
TI  - Incidence and predictors of serious bacterial infections among 57- to 180-day-old
      infants.
AB  - BACKGROUND: Numerous researchers have investigated fever in infants <2 months of
      age. However, the etiology of fever and usefulness of screening tests in older (2
      6 months) infants is not well studied. METHODS: This was a prospective study of
      febrile infants 57-180 days old. Evaluation included blood and urine tests and
      direct fluorescent antibody (DFA) of nasal swabs for respiratory viruses.
      Additional studies were performed at the discretion of managing clinicians.
      RESULTS: Serious bacterial illness (SBI) was diagnosed in 44 (10.3%) of 429
      infants: 41 with bacteruria and 4 with bacteremia (1 infant had concurrent
      Escherichia coli bacteruria and bacteremia). Lumbar puncture, performed in 58
      (13.5%) infants, revealed no cases of bacterial meningitis. DFAs were positive in
      163 (38.0%) infants: the majority were respiratory syncytial virus or influenza
      A. SBI was noted in 4.9% of infants with positive DFA. Age and height of fever
      were not significant predictors of SBI. White blood cell count (17.1 K/mm3 vs
      12.4 K/mm3) and CRP (2.6 mg/dL vs 0.9 mg/dL) were elevated in infants with SBI,
      as was the Yale Observation Score (9.4 vs 8.0). CONCLUSIONS: A substantial
      proportion (10.3%) of older febrile infants has SBI. In the postpneumococcal
      vaccine era, only 1 infant had pneumococcal disease; bacteremia was noted in
      0.9%. Bacteruria is commonly associated with fever in this age range. Infants
      older than 8 weeks remain at risk for bacteremia and bacteruria, regardless of
      positive DFA or other apparent source of fever. CRP is a better indicator than
      white blood cell count, but no single ideal indicator of SBI was identified for
      this age group.

PMID- 16651327
TI  - Azithromycin does not cure pityriasis rosea.
AB  - OBJECTIVES: Pityriasis rosea (PR) is a common skin disorder in children. Its
      cause is unknown. A recent publication reported a 73% cure rate in patients with
      PR after treatment with erythromycin. To duplicate this result using a drug with
      fewer adverse effects and greater biological half-life, we set out to study the
      effect of azithromycin on PR. Azithromycin is an azalide antibiotic with a
      spectrum of antimicrobial activity very similar to that of erythromycin. DESIGN:
      We randomly assigned 49 children with PR to receive either azithromycin (12 mg/kg
      per day, up to a maximum of 500 mg/day) for 5 days or a similar-appearing
      placebo. Study physicians were blinded to patients' treatment type. Two
      pediatricians had to agree on the diagnosis of PR before patients could be
      enrolled. Subjects were seen at follow-up visits 1, 2, and 4 weeks after starting
      treatment. OUTCOME MEASURES: We measured the appearance of new lesions and
      resolution of lesions. RESULTS: Rates of cure and of partial resolution were
      similar in the azithromycin and placebo groups. CONCLUSION: Azithromycin does not
      cure PR.

PMID- 16651328
TI  - Variation in standards of research compensation and child assent practices: a
      comparison of 69 institutional review board-approved informed permission and
      assent forms for 3 multicenter pediatric clinical trials.
AB  - OBJECTIVE: To systematically compare standards for compensation and child
      participant assent in informed permission, assent, and consent forms (IP-A-CFs)
      approved by 55 local institutional review boards (IRBs) reviewing 3 standardized
      multicenter research protocols. METHOD: Sixty-nine principal investigators
      participating in any of 3 national, multicenter clinical trials submitted
      standardized research protocols for their trials to their local IRBs for
      approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to
      an academic clinical research organization. This collection of IRB-approved forms
      allowed for a quasiexperimental retrospective evaluation of the variation in
      informed permission, assent, and consent standards operationalized by the local
      IRBs. RESULTS: Standards for compensation and child participant assent varied
      substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering
      compensation, monetary compensation was offered by 33 as reimbursement for
      travel, parking, or food expenses, whereas monetary or material compensation was
      offered by 22 for subject inconvenience and by 13 for subject time. Compensation
      ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and
      study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that
      included a form of assent documentation, 33 included a line for assent on the
      informed permission or consent form, whereas 35 included a separate form written
      in simplified language. Of the IP-A-CFs that stipulated the documentation of
      assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission
      or consent forms were addressed either to parents or child participants.
      CONCLUSION: In response to identical clinical trial protocols, local IRBs
      generate IP-A-CFs that vary considerably regarding compensation and child
      participant assent.

PMID- 16651329
TI  - The epidemiology of meconium aspiration syndrome: incidence, risk factors,
      therapies, and outcome.
AB  - OBJECTIVE: We sought to examine, in a large cohort of infants within a definable
      population of live births, the incidence, risk factors, treatments,
      complications, and outcomes of meconium aspiration syndrome (MAS). DESIGN: Data
      were gathered on all of the infants in Australia and New Zealand who were
      intubated and mechanically ventilated with a primary diagnosis of MAS (MASINT)
      between 1995 and 2002, inclusive. Information on all of the live births during
      the same time period was obtained from perinatal data registries. RESULTS: MASINT
      occurred in 1061 of 2,490,862 live births (0.43 of 1000), with a decrease in
      incidence from 1995 to 2002. A higher risk of MASINT was noted at advanced
      gestation, with 34% of cases born beyond 40 weeks, compared with 16% of infants
      without MAS. Fetal distress requiring obstetric intervention was noted in 51% of
      cases, and 42% were delivered by cesarean section. There was a striking
      association between low 5-minute Apgar score and MASINT. In addition, risk of
      MASINT was higher where maternal ethnicity was Pacific Islander or indigenous
      Australian and was also increased after planned home birth. Uptake of exogenous
      surfactant, high-frequency ventilation, and inhaled nitric oxide increased
      considerably during the study period, with >50% of infants receiving > or =1 of
      these therapies by 2002. Risk of air leak was 9.6% overall, with an apparent
      reduction to 5.3% in 2001-2002. The duration of intubation remained constant
      throughout the study period (median: 3 days), whereas duration of oxygen therapy
      and length of hospital stay increased. Death related to MAS occurred in 24
      infants (2.5% of the MASINT cohort; 0.96 per 100,000 live births). CONCLUSIONS:
      The incidence of MASINT in the developed world is low and seems to be decreasing.
      Risk of MASINT is significantly greater in the presence of fetal distress and low
      Apgar score, as well as Pacific Islander and indigenous Australian ethnicity. The
      increased use of innovative respiratory supports has not altered the duration of
      mechanical ventilation.

PMID- 16651330
TI  - Inhibition of meconium-induced cytokine expression and cell apoptosis by
      pretreatment with captopril.
AB  - OBJECTIVE: To study whether pretreatment of newborn lungs by captopril inhibits
      meconium-induced lung injury and inflammatory cytokine expression. DESIGN: Four
      groups of 2-week-old rabbit pups were used for the study: group 1, saline
      instilled rabbits; group 2, captopril-pretreated rabbits; group 3, meconium
      instilled rabbits; and group 4, captopril-pretreated and then meconium-instilled
      rabbits. Each group was studied at different time points: 0, 2, 4, 8, and 24
      hours after instillation of meconium. Experiments were done at the University of
      Illinois and Michael Reese Hospital at Chicago. After treatment and instillation
      of meconium, the right lung was fixed with formalin, and 2-mum slices were
      obtained for immunohistochemistry. The left lung was used for obtaining of lung
      lavage and measurement of total proteins (for enzyme-linked immunosorbent assay)
      and mRNA (for reverse transcription-polymerase chain reaction) purification.
      RESULTS: We found that meconium induces inflammatory cytokine expression and
      apoptotic lung cell death. In situ end labeling revealed a dramatic DNA
      fragmentation in the meconium group, which supports the presence of apoptosis.
      Using enzyme-linked immunosorbent assay, we demonstrated increase of interleukin
      6 and interleukin 8 cytokines in meconium-instilled lungs, which were
      significantly decreased in captopril-pretreated lungs. Captopril pretreatment
      also decreased meconium-induced cell death and angiotensinogen expression. We
      believe this effect is explained by the ability of captopril to decrease
      processing of ANGEN to angiotensinogen (ANG) I and finally to ANG II. It suggests
      that captopril inhibits ANG II-induced lung cell apoptosis. CONCLUSION: Our
      results demonstrate that captopril pretreatment significantly inhibits meconium
      induced lung cell death, cytokine, and ANGEN expression in newborn lungs.

PMID- 16651331
TI  - The associations among childhood headaches, emotional and behavioral
      difficulties, and health care use.
AB  - BACKGROUND: Headaches are common among children and adolescents, particularly
      migraine and tension-type headaches. They contribute to missed school days,
      affect children's peer and family relationships, and significantly impact
      children's quality of life, often times into adulthood. OBJECTIVES: This study,
      based on responses to the Strengths and Difficulties Questionnaire, was designed
      to examine difficulties and impairments related to emotions, concentration,
      behavior, and social functioning among children with frequent or severe headaches
      (FSH). METHODS: We used a cross-sectional study of 9264 children aged 4-17 years
      from the 2003 National Health Interview Survey, an ongoing, computer-assisted
      personal interview survey of the noninstitutionalized US population. RESULTS:
      Approximately 6.7% of children experienced FSH during the previous 12 months.
      Overall, children with FSH were 3.2 times more likely than children without FSH
      to have a high level of difficulties and 2.7 times more likely to have a high
      level of impairment, suggesting potential mental health issues. More
      specifically, analyses revealed that children with FSH were significantly more
      likely than those without FSH to exhibit high levels of emotional, conduct,
      inattention-hyperactivity, and peer problems and were significantly more likely
      than children without FSH to be upset or distressed by their difficulties and to
      have their difficulties interfere with home life, friendships, classroom
      learning, and leisure activities. CONCLUSION: Because children with FSH
      experience notable pain, mental health issues, and functional limitations,
      integrated care using a biopsychosocial approach is warranted.

PMID- 16651332
TI  - Pediatric hospitalists: a systematic review of the literature.
AB  - BACKGROUND: Systematic reviews have demonstrated consistently decreased length of
      stay and costs in internal medicine hospitalist systems. Systematic reviews of
      pediatric hospitalist systems have not been conducted. OBJECTIVE: Our aim was to
      determine the effects of pediatric hospitalist systems on length of stay, costs,
      quality of care, and provider satisfaction and experience. METHODS: We searched
      PubMed, Medline, Cochrane Library databases, and the Pediatric Academic Societies
      National Meeting research abstracts for all primary-data studies published or
      presented on pediatric hospitalist systems. Studies presenting primary data on
      efficiency, financial performance, clinical outcomes, or family, referring
      provider, and housestaff experience in hospitalist systems were included; review
      articles and case studies were excluded. To minimize publication bias, we
      contacted all primary authors to obtain information about unpublished studies.
      RESULTS: Of 47 publications reviewed, 20 were primary-data studies that met
      criteria for inclusion. Six of 7 studies that compared traditional and
      hospitalist systems of care demonstrated improvements in costs and/or length of
      stay in pediatric hospitalist systems. The average decrease in cost was 10%;
      average decrease in length of stay was 10%. Three of 3 economic analyses,
      however, demonstrate that efficiency gains do not generally translate into
      revenues for the hospitalist programs themselves; most hospitalist programs are
      currently losing money. Surveys of families, referring providers, and pediatric
      residents demonstrate neutral or improved experiences in hospitalist systems,
      although these data are less comprehensive. Data on quality of care are
      insufficient to draw conclusions. CONCLUSIONS: Emerging research suggests that
      pediatric hospitalist systems decrease hospital costs and length of stay without
      adversely affecting provider, parent, or housestaff experiences. The quality of
      care in pediatric hospitalist systems is unclear, because rigorous metrics to
      evaluate quality are lacking. Studies of the processes and outcomes of hospital
      care are needed.

PMID- 16651333
TI  - Environmental tobacco smoke exposure: prevalence and mechanisms of causation of
      infections in children.
AB  - BACKGROUND AND OBJECTIVES: Environmental tobacco smoke (ETS) exposure is probably
      one of the most important public health hazards in our community. Our aim with
      this article is to (1) review the prevalence of ETS exposure in the United States
      and how this prevalence is often measured in practice and (2) summarize current
      thinking concerning the mechanism by which this exposure may cause infections in
      young children. METHODS: We conducted a Medline search to obtain data published
      mainly in peer-reviewed journals. RESULTS: There is still a very high prevalence
      of ETS exposure among US children ranging from 35% to 80% depending on the method
      of measurement used and the population studied. The mechanism by which ETS may be
      related to these infections is not entirely clear but may be through suppression
      or modulation of the immune system, enhancement of bacterial adherence factors,
      or impairment of the mucociliary apparatus of the respiratory tract, or possibly
      through enhancement of toxicity of low levels of certain toxins that are not
      easily detected by conventional means. CONCLUSIONS: The prevalence of ETS
      exposure in the United States is still very high, and its role in causing
      infections in children is no longer in doubt even if still poorly understood.
      Research, therefore, should continue to focus on the various mechanisms of
      causation of these infections and how to best reduce the exposure levels.

PMID- 16651334
TI  - Should pacifiers be recommended to prevent sudden infant death syndrome?
AB  - OBJECTIVES: Our aim was to review the evidence for a reduction in the risk of
      sudden infant death syndrome (SIDS) with pacifier ("dummy" or "soother") use, to
      discuss possible mechanisms for the reduction in SIDS risk, and to review other
      possible health effects of pacifiers. RESULTS: There is a remarkably consistent
      reduction of SIDS with pacifier use. The mechanism by which pacifiers might
      reduce the risk of SIDS is unknown, but several mechanisms have been postulated.
      Pacifiers might reduce breastfeeding duration, but the studies are conflicting.
      CONCLUSIONS: It seems appropriate to stop discouraging the use of pacifiers.
      Whether it is appropriate to recommend pacifier use in infants is open to debate.

PMID- 16651335
TI  - The 75th anniversary of the American Academy of Pediatrics.

PMID- 16651336
TI  - Sickle cell disease: a question of equity and quality.
AB  - Thirty years ago, the first major federal legislation concerning sickle cell
      disease treatment was passed, resulting in the development of comprehensive
      sickle cell centers. We are now at another watershed moment in the treatment of
      this illness with the passage in October 2004 of the Sickle Cell Treatment Act,
      designed to substantially expand specialized sickle cell treatment programs. This
      legislation offers a remarkable opportunity to significantly improve health
      outcomes for individuals with sickle cell disease if it is implemented with a
      specific focus on the distinct but related issues of equity and quality. Despite
      major advances in sickle cell disease treatment that have occurred over the past
      3 decades, important gaps exist both in the equity of government and private
      philanthropic support for research and in the uniform provision of high quality
      clinical care. This article assesses the current gaps in funding support and in
      the implementation of improvements in clinical care in order to suggest
      strategies for making optimal use of the opportunity that the new legislation
      presents to improve the health of all individuals affected by this disease.

PMID- 16651337
TI  - Pediatric medicolegal education in the 21st century.

PMID- 16651338
TI  - Newborn screening technology: proceed with caution.

PMID- 16651339
TI  - We need expanded newborn screening.

PMID- 16651340
TI  - Assent in pediatric research.

PMID- 16651341
TI  - Pacifiers and sudden infant death syndrome: what should we recommend?

PMID- 16651342
TI  - Concussion in the young athlete.

PMID- 16651343
TI  - Sudden cardiac arrest in an intubated premature infant with cerebellar and
      brainstem injury: is there a link?
AB  - The ventilated premature infant frequently exhibits unprovoked desaturation
      episodes accompanied by bradycardia. In most instances, these episodes are short
      lived and recover spontaneously or with minimal interventions. However, in some
      infants these episodes may be more profound and require substantial interventions
      to restore cardiorespiratory status. Here we present the case of a ventilated
      premature infant who had experienced prolonged, multiple daily desaturation
      episodes accompanied by bradycardia that required significant interventions.
      Postoperatively, after placement of a tracheotomy and despite a patent airway,
      the infant developed acute bradycardia that progressed rapidly to sudden death.
      At autopsy, significant cerebellar and brainstem injury was noted. We hypothesize
      that the specific cerebellum and brainstem injury may have contributed to
      autonomic dysfunction and sudden death.

PMID- 16651344
TI  - The Boston Marathon Study: a novel approach to research during residency.
AB  - Resident physicians from a pediatric academic training program developed a
      hospital-wide research project in an effort to enhance their residency research
      experience. In this model, residents themselves assumed primary responsibility
      for each stage of a large prospective clinical research study. The project, which
      was integrated successfully into the residency program, enabled a large group of
      residents, with mentorship from a dedicated faculty member, to benefit from a
      structured clinical research experience while providing the flexibility necessary
      to meet the demands of a busy residency curriculum. Careful topic selection with
      a well-defined end point, faculty involvement, resident collegiality, and
      institutional support were factors identified by study leaders as central to the
      success of this model.

PMID- 16651345
TI  - Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization
      during acute otitis media.
AB  - The heptavalent pneumococcal conjugate vaccine (PCV7) has been shown to reduce
      the incidence of acute otitis media (AOM) caused by Streptococcus pneumoniae by
      34% and reduces the overall incidence of AOM by 6% to 8%. More recent studies
      have shown increases in the proportion of Haemophilus influenzae and Moraxella
      catarrhalis in the middle-ear fluid of PCV7-immunized children. There has been no
      report on the effect of PCV7 on all 3 bacterial pathogens combined, either in the
      middle-ear fluid or nasopharynx of individual children with AOM. We investigated
      the impact of PCV7 on nasopharyngeal colonization with bacterial pathogens during
      AOM in the pre-PCV7 and post-PCV7 vaccination eras. Four hundred seventeen
      children (6 months to 4 years of age) were enrolled onto AOM studies between
      September 1995 and December 2004. Of these, 200 were enrolled before the vaccine
      use (historical controls), and 217 were enrolled after the initiation of PCV7
      vaccination (101 were underimmunized, and 116 were immunized). Although the
      nasopharyngeal colonization rate for S pneumoniae was not different between the 3
      groups, a significantly higher proportion of PCV7-immunized children with AOM
      were colonized with M catarrhalis. Overall, the mean number of pathogenic
      bacteria types isolated from immunized children (1.7) was significantly higher
      than in controls (1.4). The increase in bacterial colonization of the nasopharynx
      during AOM could be associated with an increase in AOM pathogens and
      theoretically can predispose PCV7-immunized children with AOM to a higher rate of
      antibiotic treatment failure or recurrent AOM.

PMID- 16651346
TI  - Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac
      troponin T gene.
AB  - Here we report the first infantile case of restrictive cardiomyopathy caused by a
      de novo mutation of the cardiac troponin T gene. The patient presented with an
      apparent life-threatening event. She developed malignant arrhythmias and
      hemodynamic instability, requiring initial rescue support with extracorporeal
      membrane oxygenation, and subsequently underwent insertion of a biventricular
      assist device (VAD). She successfully received an orthotopic heart transplant 172
      days after VAD implantation.

PMID- 16651347
TI  - Active healthy living: prevention of childhood obesity through increased physical
      activity.
AB  - The current epidemic of inactivity and the associated epidemic of obesity are
      being driven by multiple factors (societal, technologic, industrial, commercial,
      financial) and must be addressed likewise on several fronts. Foremost among these
      are the expansion of school physical education, dissuading children from pursuing
      sedentary activities, providing suitable role models for physical activity, and
      making activity-promoting changes in the environment. This statement outlines
      ways that pediatric health care providers and public health officials can
      encourage, monitor, and advocate for increased physical activity for children and
      teenagers.

PMID- 16651348
TI  - Ophthalmologic examinations in children with juvenile rheumatoid arthritis.
AB  - Unlike the joints, ocular involvement with juvenile rheumatoid arthritis is most
      often asymptomatic; yet, the inflammation can cause serious morbidity with loss
      of vision. Scheduled slit-lamp examinations by an ophthalmologist at specific
      intervals can detect ocular disease early, and prompt treatment can prevent
      vision loss.

PMID- 16651349
TI  - The pacifier debate.

PMID- 16651350
TI  - The pacifier debate.

PMID- 16651351
TI  - The pacifier debate.

PMID- 16651352
TI  - Physiomarkers of neonatal heart rate.

PMID- 16651353
TI  - Intensivist-led team approach to critical care of children with heart disease.

PMID- 16651354
TI  - Ampicillin and cefotaxime as a risk factor of neonatal death.

PMID- 16651355
TI  - Is it safer to intubate premature infants in the delivery room?

PMID- 16651356
TI  - Maternal anxiety impairs lactation initiation and maintenance.

PMID- 16651357
TI  - Masturbation in infancy and early childhood presenting as a movement disorder.

PMID- 16651358
TI  - Administration of epinephrine for life-threatening allergic reactions in school
      settings.

PMID- 16651359
TI  - High-dose indomethacin for patent ductus arteriosus closure: how strong is the
      evidence?

PMID- 16651360
TI  - Therapeutic nihilism in Duchenne cardiomyopathy.

PMID- 16651361
TI  - Psychosocial implications of disaster on children and pediatric care.

PMID- 16651362
TI  - Hypertrophic cardiomyopathy in preterm infants treated with methylprednisolone
      for bronchopulmonary dysplasia.

PMID- 16651363
TI  - Effects of growth hormone treatment on neutrophil count in children born small
      for gestational age.

PMID- 16651364
TI  - Research for newborn screening: developing a national framework.

PMID- 16651365
TI  - Genome-wide location analysis: insights on transcriptional regulation.
AB  - Gene expression analysis of microarray data can provide a global view of the
      transcriptome of a cell or specific tissue type, revealing important information
      about the kinds of signaling pathways, genes and protein classifications that are
      active. However, transcript profiles alone do not reveal how expression levels
      are controlled or which transcription factors (TFs) are responsible. Establishing
      transcriptional regulatory networks requires knowledge of TFs bound to promoter,
      enhancer and repressor elements. Accessibility of these sites and an additional
      level of control are mediated by chromatin and DNA modifications. Genome-wide
      location analysis is a tool for identifying protein-DNA interaction sites on a
      genomic scale. Applications of this tool are proving invaluable in determining in
      vivo target genes of TFs, epigenetic marks and cis-regulatory elements. Here, we
      will discuss how advances have been made in each of these categories and how this
      has helped to elucidate regulatory networks and control mechanisms.

PMID- 16651366
TI  - Non-coding RNA.
AB  - The term non-coding RNA (ncRNA) is commonly employed for RNA that does not encode
      a protein, but this does not mean that such RNAs do not contain information nor
      have function. Although it has been generally assumed that most genetic
      information is transacted by proteins, recent evidence suggests that the majority
      of the genomes of mammals and other complex organisms is in fact transcribed into
      ncRNAs, many of which are alternatively spliced and/or processed into smaller
      products. These ncRNAs include microRNAs and snoRNAs (many if not most of which
      remain to be identified), as well as likely other classes of yet-to-be-discovered
      small regulatory RNAs, and tens of thousands of longer transcripts (including
      complex patterns of interlacing and overlapping sense and antisense transcripts),
      most of whose functions are unknown. These RNAs (including those derived from
      introns) appear to comprise a hidden layer of internal signals that control
      various levels of gene expression in physiology and development, including
      chromatin architecture/epigenetic memory, transcription, RNA splicing, editing,
      translation and turnover. RNA regulatory networks may determine most of our
      complex characteristics, play a significant role in disease and constitute an
      unexplored world of genetic variation both within and between species.

PMID- 16651367
TI  - From genome to proteome: developing expression clone resources for the human
      genome.
AB  - cDNA clones have long been valuable reagents for studying the structure and
      function of proteins. With recent access to the entire human genome sequence, it
      has become possible and highly productive to compare the sequences of mRNAs to
      their genes, in order to validate the sequences and protein-coding annotations of
      each (1,2). Thus, well-characterized collections of human cDNAs are now playing
      an essential role in defining the structure and function of human genes and
      proteins. In this review, we will summarize the major collections of human cDNA
      clones, discuss some limitations common to most of these collections and describe
      several noteworthy proteomics applications, focusing on the detection and
      analysis of protein-protein interactions (PPI). These human cDNA collections
      contain principally two types of cDNA clones. The largest collections comprise
      cDNAs with full-length protein coding sequences (FL-CDS). Some but not all of
      these cDNA clones may represent the entire mRNA sequence, but many are missing
      considerable non-coding UTR sequence, usually at the 5' end. A second type of
      cDNA clone, a 'full-ORF' (F-ORF) expression clone, is one where the annotated
      protein-coding sequence, excised of 5' UTR and 3' UTR sequence, has been
      transferred to a vector designed to facilitate transfer to other vectors for
      protein expression.

PMID- 16651368
TI  - Ethical issues in medical-sequencing research: implications of genotype-phenotype
      studies for individuals and populations.
AB  - Advances and declining costs in sequencing technology will result in increasing
      number of studies with individual sequence data linked to phenotypic information,
      which has been dubbed medical sequencing. At least some of this linked
      information will be publicly available. Medical sequencing raises ethical issues
      for both individuals and populations, including data release and identifiability,
      adequacy of consent, reporting research results, stereotyping and stigmatization,
      inclusion and differential benefit and culturally and community-specific
      concerns. Those issues are reviewed, along with possible solutions to them.

PMID- 16651369
TI  - Evolution at the nucleotide level: the problem of multiple whole-genome
      alignment.
AB  - With the genome sequences of numerous species at hand, we have the opportunity to
      discover how evolution has acted at each and every nucleotide in our genome. To
      this end, we must identify sets of nucleotides that have descended from a common
      ancestral nucleotide. The problem of identifying evolutionary-related nucleotides
      is that of sequence alignment. When the sequences under consideration are entire
      genomes, we have the problem of multiple whole-genome alignment. In this paper,
      we first state a series of definitions for homology and its subrelations between
      single nucleotides. Within this framework, we review the current methods
      available for the alignment of multiple large genomes. We then describe a subset
      of tools that make biological inferences from multiple whole-genome alignments.

PMID- 16651370
TI  - Structural variants: changing the landscape of chromosomes and design of disease
      studies.
AB  - The near completeness of human chromosome sequences is facilitating accurate
      characterization and assessment of all classes of genomic variation.
      Particularly, using the DNA reference sequence as a guide, genome scanning
      technologies, such as microarray-based comparative genomic hybridization (array
      CGH) and genome-wide single nucleotide polymorphism (SNP) platforms, have now
      enabled the detection of a previously unrecognized degree of larger-sized (non
      SNP) variability in all genomes. This heterogeneity can include copy number
      variations (CNVs), inversions, insertions, deletions and other complex
      rearrangements, most of which are not detected by standard cytogenetics or DNA
      sequencing. Although these genomic alterations (collectively termed structural
      variants or polymorphisms) have been described previously, mainly through locus
      specific studies, they are now known to be more global in occurrence. Moreover,
      as just one example, CNVs can contain entire genes and their number can correlate
      with the level of gene expression. It is also plausible that structural variants
      may commonly influence nearby genes through chromosomal positional or domain
      effects. Here, we discuss what is known of the prevalence of structural variants
      in the human genome and how they might influence phenotype, including the
      continuum of etiologic events underlying monogenic to complex diseases.
      Particularly, we highlight the newest studies and some classic examples of how
      structural variants might have adverse genetic consequences. We also discuss why
      analysis of structural variants should become a vital step in any genetic study
      going forward. All these progresses have set the stage for a golden era of
      combined microscopic and sub-microscopic (cytogenomic)-based research of
      chromosomes leading to a more complete understanding of the human genome.

PMID- 16651371
TI  - Lessons from studying monogenic disease for common disease.

PMID- 16651372
TI  - Sleeping beauty: a novel cancer gene discovery tool.
AB  - The National Cancer Institute and the National Human Genome Research Institute
      recently announced a 3-year 100-million-dollar pilot study to use large-scale
      resequencing of genes in human tumors to identify new cancer genes. The hope is
      that some of these genes can be used as drug targets for developing better
      therapeutics for treating cancer. Although this effort will identify new cancer
      genes, it could be made more efficient by preferentially resequencing genes
      identified as novel candidate cancer genes in animal models of cancer. Although
      retroviral insertional mutagenesis has proven to be an effective tool for
      identifying novel cancer genes in the mouse, these studies are limited by the
      fact that retroviral mutagenesis primarily induces hematopoietic and mammary
      cancer, but little else, while the majority of cancers affecting humans are solid
      tumors. Recently, two groups have shown that sleeping beauty (SB) transposon
      based insertional mutagenesis can also identify novel candidate cancer genes in
      the mouse. Unlike retroviral infection, SB transposition can be controlled to
      mutagenize any target tissue and thus potentially induce many different kinds of
      cancer, including solid tumors. SB transposition in animal models of cancer could
      therefore greatly facilitate the identification of novel human cancer genes and
      the development of better cancer therapies.

PMID- 16651373
TI  - Integrating biological data through the genome.
AB  - Owing to the ongoing success of the genome sequencing and structural genomics
      projects, the increase in both sequence and structural data is rapid. The
      development of tools for the annotation of sequence and structural data has
      become more important in the hope of keeping up with this data explosion.
      Scientists in this field have addressed these issues over the last 10 years and
      there now exists a wealth of methods and approaches to help interpret these data.
      However, there is no current way in which these methods can be incorporated
      easily so that the resulting annotations can be viewed together. This review
      discusses the development of these annotation methods and introduces the
      BioSapiens Network of Excellence, which has been formed in order to integrate the
      methods which have been developed in Europe.

PMID- 16651374
TI  - Pharmacogenomics: from bedside to clinical practice.
AB  - The field of pharmacogenomics has seen some exciting advances in the recent past.
      The Human Genome Project and International HapMap projects have uncovered a
      wealth of information for researchers. The discovery of clinically predictive
      genotypes (e.g. UGT1A1*28, TYMS TSER), haplotypes (e.g. VKORC1 Haplotype A) and
      somatic mutations (e.g. epidermal growth factor receptor), along with the
      introduction of FDA approved pharmacogenetic tests (UGT1A1*28) and the initiation
      of a genotype-guided clinical trial for cancer therapy (TYMS TSER in rectal
      cancer) have provided the first steps towards the integration of pharmacogenomics
      into clinical practice. This review describes some of the recent advances in
      pharmacogenomics research.

PMID- 16651375
TI  - Influence of human genome polymorphism on gene expression.
AB  - Genetic variation, through its effects on gene expression, plays a crucial role
      in phenotypic variation and disease susceptibility. Recent studies from our group
      and others have integrated a number of resources and technologies to assess
      several aspects of genome variation affecting gene expression. Some of these
      large-scale mapping studies involving expression quantitative traits have
      recently been reviewed [Gibson, G. and Weir, B. (2005) The quantitative genetics
      of transcription. Trends Genet., 21, 616-623; de Koning, D.J. and Haley, C.S.
      (2005) Genetical genomics in humans and model organisms. Trends Genet., 21, 377
      381], with particular attention to the statistical issues. In this review, we
      compare allele-specific expression studies in human samples (primarily
      lymphoblastoid cell lines from the CEPH HapMap panel), as a prelude to a
      discussion on study design issues and sources of variation, in order to propose
      the steps required to build a detailed map of cis-acting regulatory variation in
      the human genome. Obtaining panels of tissues from large numbers of individuals
      remains an important limitation. We also conclude that there is insufficient
      knowledge as to the feasibility of comprehensive studies of trans-acting
      variation in the human genome.

PMID- 16651376
TI  - The emerging science of epigenomics.
AB  - One of the most exciting frontiers in both epigenetics and genome sciences is the
      new field of epigenomics. This new discipline promises novel insights into the
      genome because of its potential to detect quantitative alterations, multiplex
      modifications and regulatory sequences outside of genes. A number of new
      epigenomic strategies are emerging to exploit microarray formats with varying
      substrate choice, pre-processing and data analysis. These approaches are designed
      to detect large numbers of variations in DNA methylation and chromatin
      modification. Many groups are joining forces toward developing an organized Human
      Epigenome Project to exploit these new technologies to better understand the
      basis of normal development and human disease.

PMID- 16651377
TI  - Distinct mechanisms regulate hemocyte chemotaxis during development and wound
      healing in Drosophila melanogaster.
AB  - Drosophila melanogaster hemocytes are highly motile macrophage-like cells that
      undergo a stereotypic pattern of migration to populate the whole embryo by late
      embryogenesis. We demonstrate that the migratory patterns of hemocytes at the
      embryonic ventral midline are orchestrated by chemotactic signals from the
      PDGF/VEGF ligands Pvf2 and -3 and that these directed migrations occur
      independently of phosphoinositide 3-kinase (PI3K) signaling. In contrast, using
      both laser ablation and a novel wounding assay that allows localized treatment
      with inhibitory drugs, we show that PI3K is essential for hemocyte chemotaxis
      toward wounds and that Pvf signals and PDGF/VEGF receptor expression are not
      required for this rapid chemotactic response. Our results demonstrate that at
      least two separate mechanisms operate in D. melanogaster embryos to direct
      hemocyte migration and show that although PI3K is crucial for hemocytes to sense
      a chemotactic gradient from a wound, it is not required to sense the growth
      factor signals that coordinate their developmental migrations along the ventral
      midline during embryogenesis.

PMID- 16651378
TI  - Notch signaling via Hes1 transcription factor maintains survival of melanoblasts
      and melanocyte stem cells.
AB  - Melanoblasts (Mbs) are thought to be strictly regulated by cell-cell interactions
      with epidermal keratinocytes, although the precise molecular mechanism of the
      regulation has been elusive. Notch signaling, whose activation is mediated by
      cell-cell interactions, is implicated in a broad range of developmental
      processes. We demonstrate the vital role of Notch signaling in the maintenance of
      Mbs, as well as melanocyte stem cells (MSCs). Conditional ablation of Notch
      signaling in the melanocyte lineage leads to a severe defect in hair
      pigmentation, followed by intensive hair graying. The defect is caused by a
      dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of
      Hes1 is sufficient to protect Mbs from the elimination by apoptosis. Thus, these
      data provide evidence that Notch signaling, acting through Hes1, plays a crucial
      role in the survival of immature Mbs by preventing initiation of apoptosis.

PMID- 16651379
TI  - A functional network involved in the recycling of nucleocytoplasmic pre-60S
      factors.
AB  - Eukaryotic pre-ribosomes go through cytoplasmic maturation steps before entering
      translation. The nucleocytoplasmic proteins participating in these late stages of
      maturation are reimported to the nucleus. In this study, we describe a functional
      network focused on Rei1/Ybr267w, a strictly cytoplasmic pre-60S factor indirectly
      involved in nuclear 27S pre-ribosomal RNA processing. In the absence of Rei1, the
      nuclear import of at least three other pre-60S factors is impaired. The
      accumulation in the cytoplasm of a small complex formed by the association of
      Arx1 with a novel factor, Alb1/Yjl122w, inhibits the release of the putative
      antiassociation factor Tif6 from the premature large ribosomal subunits and its
      recycling to the nucleus. We propose a model in which Rei1 is a key factor for
      the coordinated dissociation and recycling of the last pre-60S factors before
      newly synthesized large ribosomal subunits enter translation.

PMID- 16651380
TI  - The activity status of cofilin is directly related to invasion, intravasation,
      and metastasis of mammary tumors.
AB  - Understanding the mechanisms controlling cancer cell invasion and metastasis
      constitutes a fundamental step in setting new strategies for diagnosis,
      prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of
      a novel class of serine-threonine protein kinases. Cofilin, a LIMK1 substrate, is
      essential for the regulation of actin polymerization and depolymerization during
      cell migration. Previous studies have made opposite conclusions as to the role of
      LIMK1 in tumor cell motility and metastasis, claiming either an increase or
      decrease in cell motility and metastasis as a result of LIMK1 over expression
      (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis.
      2000. J. Cell Biol. 151:1119-1128; Davila, M., A.R. Frost, W.E. Grizzle, and R.
      Chakrabarti. 2003. J. Biol. Chem. 278:36868-36875; Yoshioka, K., V. Foletta, O.
      Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247-7252; Nishita,
      M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell
      Biol. 171:349-359). We resolve this paradox by showing that the effects of LIMK1
      expression on migration, intravasation, and metastasis of cancer cells can be
      most simply explained by its regulation of the output of the cofilin pathway.
      LIMK1-mediated decreases or increases in the activity of the cofilin pathway are
      shown to cause proportional decreases or increases in motility, intravasation,
      and metastasis of tumor cells.

PMID- 16651381
TI  - Stress fibers are generated by two distinct actin assembly mechanisms in motile
      cells.
AB  - Stress fibers play a central role in adhesion, motility, and morphogenesis of
      eukaryotic cells, but the mechanism of how these and other contractile actomyosin
      structures are generated is not known. By analyzing stress fiber assembly
      pathways using live cell microscopy, we revealed that these structures are
      generated by two distinct mechanisms. Dorsal stress fibers, which are connected
      to the substrate via a focal adhesion at one end, are assembled through formin
      (mDia1/DRF1)-driven actin polymerization at focal adhesions. In contrast,
      transverse arcs, which are not directly anchored to substrate, are generated by
      endwise annealing of myosin bundles and Arp2/3-nucleated actin bundles at the
      lamella. Remarkably, dorsal stress fibers and transverse arcs can be converted to
      ventral stress fibers anchored to focal adhesions at both ends. Fluorescence
      recovery after photobleaching analysis revealed that actin filament cross-linking
      in stress fibers is highly dynamic, suggesting that the rapid association
      dissociation kinetics of cross-linkers may be essential for the formation and
      contractility of stress fibers. Based on these data, we propose a general model
      for assembly and maintenance of contractile actin structures in cells.

PMID- 16651382
TI  - Competitive intra- and extracellular nutrient sensing by the transporter
      homologue Ssy1p.
AB  - Recent studies of Saccharomyces cerevisiae revealed sensors that detect
      extracellular amino acids (Ssy1p) or glucose (Snf3p and Rgt2p) and are
      evolutionarily related to the transporters of these nutrients. An intriguing
      question is whether the evolutionary transformation of transporters into
      nontransporting sensors reflects a homeostatic capability of transporter-like
      sensors that could not be easily attained by other types of sensors. We
      previously found SSY1 mutants with an increased basal level of signaling and
      increased apparent affinity to sensed extracellular amino acids. On this basis,
      we propose and test a general model for transporter- like sensors in which
      occupation of a single, central ligand binding site increases the activation
      energy needed for the conformational shift between an outward-facing, signaling
      conformation and an inward-facing, nonsignaling conformation. As predicted,
      intracellular leucine accumulation competitively inhibits sensing of
      extracellular amino acids. Thus, a single sensor allows the cell to respond to
      changes in nutrient availability through detection of the relative concentrations
      of intra- and extracellular ligand.

PMID- 16651383
TI  - Influenza: current threat from avian influenza.
AB  - Influenza is an infectious respiratory pathogen causing annual outbreaks and
      infrequent pandemics, resulting in significant morbidity, mortality and burdens
      on the delivery of health care. The geographical spread of highly pathogenic
      avian influenza (HPAI) H5N1 among poultry and wild bird populations is
      unprecedented. Growing numbers of sporadic avian influenza infections are
      occurring in humans, increasing the threat of the next influenza pandemic.
      Vaccines are the principle means of combating influenza, and a number of studies
      with H5N1 vaccine candidates are underway. Antiviral agents can be used to treat
      influenza infection and can be taken as chemoprophylaxis during influenza
      outbreaks. Oseltamivir has been stockpiled as part of influenza pandemic
      preparedness planning; however, the emergence of drug resistance may limit its
      clinical use.

PMID- 16651384
TI  - Bax does not have to adopt its final form to drive T cell death.
AB  - The introduction of antigen into animals causes antigen-specific T cells to
      divide and then die. Activated T cell death requires either of the death effector
      molecules, Bak or Bax. When T cells die, Bak and Bax change their conformations,
      a phenomenon that is thought to be required for Bak or Bax to drive cell death.
      Here we show that Bak changes conformation before activated T cells die, as
      detected by an antibody specific for a peptide near the NH2 terminus of Bak, but
      Bax does not change its shape markedly until after the cells are dead, as
      detected by an antibody specific for a peptide near the NH2 terminus of Bax. This
      latter finding is also true in activated T cells that lack Bak and are therefore
      dependent on Bax to die. This result suggests that Bax does not have to adopt its
      final, completely unfolded form until after the cells are dead.

PMID- 16651385
TI  - A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis.
AB  - Telomerase is a ribonucleoprotein complex consisting of two essential core
      components: a reverse transcriptase and an RNA subunit (telomerase RNA [TR]).
      Dysregulation of telomerase has been associated with cell immortalization and
      oncogenesis. Marek's disease herpesvirus (MDV) induces a malignant T cell
      lymphoma in chickens and harbors in its genome two identical copies of a viral TR
      (vTR) with 88% sequence identity to chicken TR. MDV mutants lacking both copies
      of vTR were significantly impaired in their ability to induce T cell lymphomas,
      although lytic replication in vivo was unaffected. Tumor incidences were reduced
      by >60% in chickens infected with vTR- viruses compared with animals inoculated
      with MDV harboring at least one intact copy of vTR. Lymphomas in animals infected
      with the vTR- viruses were also significantly smaller in size and less
      disseminated. Constitutive expression of vTR in the chicken fibroblast cell line
      DF-1 resulted in a phenotype consistent with transformation as indicated by
      morphological alteration, enhanced anchorage-independent cell growth, cell growth
      beyond saturation density, and increased expression levels of integrin alpha v.
      We concluded that vTR plays a critical role in MDV-induced T cell
      lymphomagenesis. Furthermore, our results provide the first description of tumor
      promoting effects of TR in a natural virus-host infection model.

PMID- 16651386
TI  - Protective immune responses against West Nile virus are primed by distinct
      complement activation pathways.
AB  - West Nile virus (WNV) causes a severe infection of the central nervous system in
      several vertebrate animals including humans. Prior studies have shown that
      complement plays a critical role in controlling WNV infection in complement (C)
      3(-/-) and complement receptor 1/2(-/-) mice. Here, we dissect the contributions
      of the individual complement activation pathways to the protection from WNV
      disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in
      increased mortality in mice, suggesting that all activation pathways function
      together to limit WNV spread. In the absence of alternative pathway complement
      activation, WNV disseminated into the central nervous system at earlier times and
      was associated with reduced CD8+ T cell responses yet near normal anti-WNV
      antibody profiles. Animals lacking the classical and lectin pathways had deficits
      in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q
      was required for productive infection in the spleen but not for development of
      adaptive immune responses after WNV infection. Our results suggest that
      individual pathways of complement activation control WNV infection by priming
      adaptive immune responses through distinct mechanisms.

PMID- 16651387
TI  - Mechanisms imposing the Vbeta bias of Valpha14 natural killer T cells and
      consequences for microbial glycolipid recognition.
AB  - Mouse and human natural killer T (NKT) cells recognize a restricted set of
      glycosphingolipids presented by CD1d molecules, including self iGb3 and microbial
      alpha-glycuronosylceramides. The importance of the canonical Valpha14-Jalpha18
      TCR alpha chain for antigen recognition by NKT cells is well recognized, but the
      mechanisms underlying the Vbeta8, Vbeta7, and Vbeta2 bias in mouse have not been
      explored. To study the influences of thymic selection and the constraints of
      pairing with Valpha14-Jalpha18, we have created a population of mature T cells
      expressing Valpha14-Jalpha18 TCR alpha chain in CD1d-deficient mice and studied
      its recognition properties in vitro and in vivo. Transgenic cells expressed a
      diverse Vbeta repertoire but their recognition of endogenous ligands and
      synthetic iGb3 was restricted to the same biased Vbeta repertoire as expressed in
      natural NKT cells. In contrast, alpha-GalCer, a synthetic homologue of microbial
      alpha-glycuronosylceramides, was recognized by a broader set of Vbeta chains,
      including the biased NKT set but also Vbeta6, Vbeta9, Vbeta10, and Vbeta14. These
      surprising findings demonstrate that, whereas Vbeta8, Vbeta7, and Vbeta2
      represent the optimal solution for recognition of endogenous ligand, many Vbeta
      chains that are potentially useful for the recognition of foreign lipids fail to
      be selected in the NKT cell repertoire.

PMID- 16651388
TI  - Immunolocalization of full-length NK1 tachykinin receptors in human tumors.
AB  - Biological effects of substance P (SP) are mediated by the neurokinin-1 (NK1)
      receptor that exists as a full-length and as a carboxy-terminally truncated
      isoform in humans. Although NK1 receptor mRNA and binding sites have been
      detected in certain malignancies, little is known about the cellular and
      subcellular localization of NK1 receptor protein in human neoplastic tissues. We
      developed and characterized a novel anti-peptide antibody to the carboxy-terminal
      region of the human full-length NK1 receptor. Specificity of the antiserum was
      demonstrated by (1) detection of a broad band migrating at molecular mass 70,000
      90,000 Da in Western blots of membranes from NK1-expressing tissues; (2) cell
      surface staining of NK1-transfected cells; (3) translocation of NK1 receptor
      immunostaining after SP exposure; and (4) abolition of tissue immunostaining by
      preadsorption of the antibody with its immunizing peptide. Distribution of NK1
      receptors was investigated in 72 formalin-fixed, paraffin-embedded human tumors
      showing that NK1 receptors were frequently expressed in glioblastomas and breast
      and pancreatic carcinomas. Immunoreactive NK1 receptors were clearly confined to
      the plasma membrane and uniformly present on nearly all tumor cells. Development
      of this novel NK1 receptor antibody allows the efficient localization of NK1
      receptor protein in human formalin-fixed, paraffin-embedded tissues. NK1 receptor
      visualization with this simple and rapid immunohistochemical method will
      facilitate identification of tumors with a sufficient receptor overexpression for
      diagnostic or therapeutic intervention using SP analogs.

PMID- 16651389
TI  - Differential expression and subcellular localization of claudin-7, -8, -12, -13,
      and -15 along the mouse intestine.
AB  - Among tight-junction proteins, claudins, which play a key role in paracellular
      transport across epithelia, claudins 1 to 5 are expressed in the intestine, and
      changes in their abundance and/or distribution are considered to contribute to
      various gastrointestinal diseases. We investigated, by reverse transcription-PCR,
      immunoblot, and immunofluorescence analyses, which other claudin species were
      expressed in the mouse intestine, and whether they showed unique expression
      profiles. Rabbit polyclonal antibodies against mouse claudin-8, claudin-12, and
      claudin-15 were generated, and their specificity was verified by immunoblotting
      using COS-7 cells transfected with individual claudin cDNAs. Claudin-7, -8, -12, 
      13, and -15 appeared to be expressed in the duodenum, jejunum, ileum, and/or
      colon with remarkable variations in the expression levels along the intestinal
      tract, and had distinct subcellular localization in the intestinal epithelium. In
      addition, claudin-13 and -15 exhibited gradients along the crypt-surface axis of
      the colon. By contrast, claudin-6, -9, -10, -11, -14, -16, -18, and -19 were not
      observed in the intestine. Our results indicate that five additional species of
      claudins have very complex expression patterns along and within the intestine,
      and that this may reflect differences in paracellular permeable properties,
      providing valuable resources for studying the significance of these claudins in
      gastrointestinal disorders. This manuscript contains online supplemental material
      available at http://www.jhc.org. Please visit this article online to view these
      materials.

PMID- 16651390
TI  - Differential expression of cell surface markers by ovine respiratory tract
      dendritic cells.
AB  - Dendritic cells (DCs) are key antigen-presenting cells central to the induction
      of primary immune responses. Despite the prevalence of respiratory disease in
      sheep and the increasing use of the ovine lung as a model for human disease,
      ovine respiratory tract DCs (RTDCs) have not yet been characterized. Using single
      and double immunocytochemical staining, expression of a number of potential DC
      markers (MHC class II, CD1b, SIRPalpha, and CD205) by ovine RTDC populations has
      been determined. MHC class II staining revealed widespread populations of DCs
      either adjacent to respiratory airway epithelium or within the lung parenchyma.
      CD1b was expressed by a small subpopulation of both airway and parenchymal RTDCs.
      Expression of SIRPalpha was limited to a small subpopulation of airway RTDCs but
      was absent from the lung parenchyma. CD205 was widely expressed by airway RTDCs
      but expressed only by a small subpopulation of parenchymal RTDCs. In addition,
      the majority (87%) of parenchymal CD205+ cells exhibited a non-DC-like morphology
      and did not express MHC class II, suggesting that these single CD205+ cells were
      not DCs. Phenotypic differences between airway and parenchymal RTDCs may be
      related to functional differences between the two populations.

PMID- 16651391
TI  - Expression of bone morphogenic proteins and receptors at the injured growth plate
      cartilage in young rats.
AB  - The injured growth plate cartilage is often repaired by bony tissue, resulting in
      impaired bone growth in children. Bone morphogenic proteins (BMPs) are important
      for bone fracture repair, and as a step to characterize potential involvement of
      BMPs in bony repair of injured growth plate, expression of BMPs and receptors
      (BMP-R) was examined by quantitative RT-PCR and immunohistochemistry in rat
      injured tibial growth plate. During the inflammatory response on day 1, slightly
      increased expression of BMP-3, BMP-4, BMP-R1a, and BMP-R2 was observed, with
      immunostaining seen among inflammatory cells at the injury site. During
      mesenchymal infiltration and osteogenic responses on days 3-14, moderately
      increased expression of BMP-2, -3, -4, -7, and BMP-R1a was found, with
      immunostaining observed among infiltrated mesenchymal cells and differentiated
      osteoblasts lining bony trabeculae. During maturation phase on days 14-25, only
      BMP-7 was seen upregulated slightly and was localized in osteoblasts and marrow
      cells at the injury site. The temporospatial expression of BMPs and receptors at
      the injured growth plate suggests potential involvement of BMP-3 and -4 in
      regulating the inflammatory response or as its mediators in modulating downstream
      events, and BMP-2, -3, -4, and -7 in the fibrogenic and osteogenic responses, and
      BMP-7 in bone remodeling at the injured growth plate.

PMID- 16651392
TI  - Expression of enzymes involved in estrogen metabolism in human prostate.
AB  - There is evidence that estrogens can directly modulate human prostate cell
      activity. It has also been shown that cultured human prostate cancer LNCaP can
      synthesize the active estrogen estradiol (E2). To elucidate the metabolism of
      estrogens in the human prostate, we have studied the expression of enzymes
      involved in the formation and inactivation of estrogens at the cellular level.
      17beta-Hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 4, 7, and 12, as
      well as aromatase mRNA and protein expressions, were studied in benign prostatic
      hyperplasia (BPH) specimens using in situ hybridization and immunohistochemistry.
      For 17beta-HSD type 4, only in situ hybridization studies were performed.
      Identical results were obtained with in situ hybridization and
      immunohistochemistry. All the enzymes studied were shown to be expressed in both
      epithelial and stromal cells, with the exception of 17beta-HSD types 4 and 7,
      which were detected only in the epithelial cells. On the basis of our previous
      results, showing that 3beta-HSD and 17beta-HSD type 5 are expressed in human
      prostate, and of the present data, it can be concluded that the human prostate
      expresses all the enzymes involved in the conversion of circulating
      dehydroepiandrosterone (DHEA) to E2. The local biosynthesis of E2 might be
      involved in the development and/or progression of prostate pathology such as BPH
      and prostate cancer through modulation of estrogen receptors, which are also
      expressed in epithelial and stromal cells.

PMID- 16651393
TI  - Localization of extracellular matrix receptors on the chondrocyte primary cilium.
AB  - A single primary cilium is found in chondrocytes and other connective tissue
      cells. We have previously shown that extracellular matrix (ECM) macromolecules
      such as collagen fibers closely associate with chondrocyte primary cilia, and
      their points of contact are characterized by electron-opaque plaques suggesting a
      direct link between the ECM and the cilium. This study examines the expression of
      receptors for ECM molecules on chondrocyte primary cilia. Embryonic chick sterna
      were fluorescently labeled with antibodies against alpha and beta integrins, NG2,
      CD44, and annexin V. Primary cilia were labeled using acetylated alpha-tubulin
      antibody. Expression of ECM receptors was examined on chondrocyte plasma
      membranes and their primary cilia using immunofluorescence and confocal
      microscopy. All receptors examined showed a punctate distribution on the plasma
      membrane. alpha2, alpha3, and beta1 integrins and NG2 were also present on
      primary cilia, whereas annexin V and CD44 were excluded. The number of receptor
      positive cilia varied from 8/50 for NG2 to 43/50 for beta1 integrin. This is the
      first study to demonstrate the expression of integrins and NG2 on chondrocyte
      primary cilia. The data strongly suggest that chondrocyte primary cilia have the
      necessary machinery to act as mechanosensors, linking the ECM to cytoplasmic
      organelles responsible for matrix production and secretion.

PMID- 16651394
TI  - What do we know about health care team effectiveness? A review of the literature.
AB  - This review of health care team effectiveness literature from 1985 to 2004
      distinguishes among intervention studies that compare team with usual (nonteam)
      care; intervention studies that examine the impact of team redesign on team
      effectiveness; and field studies that explore relationships between team context,
      structure, processes, and outcomes. The authors use an Integrated Team
      Effectiveness Model (ITEM) to summarize research findings and to identify gaps in
      the literature. Their analysis suggests that the type and diversity of clinical
      expertise involved in team decision making largely accounts for improvements in
      patient care and organizational effectiveness. Collaboration, conflict
      resolution, participation, and cohesion are most likely to influence staff
      satisfaction and perceived team effectiveness. The studies examined here
      underscore the importance of considering the contexts in which teams are
      embedded. The ITEM provides a useful framework for conceptualizing relationships
      between multiple dimensions of team context, structure, processes, and outcomes.

PMID- 16651395
TI  - Regulatory perspectives on pharmacogenomics: a review of the literature on key
      issues faced by the United States Food and Drug Administration.
AB  - Pharmacogenomics (PGx), the use of genetic information to individualize drug
      therapy, is an immediate and important application of the Human Genome Project.
      The advent of PGx presents challenges to the U.S. Food and Drug Administration
      (FDA) in pursuing its mandate of protecting public health and safety. The authors
      conducted a review of academic, industry, and government literature using a
      technology diffusion framework to identify issues faced by the FDA relevant to
      the application of PGx. Two hundred and ten articles were reviewed. Key issues
      were categorized as rationale and structure for PGx regulation, regulation of PGx
      based testing technologies, regulation of applications in clinical settings,
      regulation of data, and regulation of product life cycles. This review identifies
      issues faced by the FDA with respect to PGx, which the FDA is addressing through
      several initiatives. It also illustrates the complex issues involved in
      developing, implementing, and adopting new technologies.

PMID- 16651396
TI  - Hospital inpatient costs for adults with multiple chronic conditions.
AB  - This article offers national estimates of the proportions of hospital inpatient
      cases and cost for adult, nonmaternal patients who have multiple chronic
      conditions. The authors employ a refined classification of chronic versus acute
      conditions, collapsed to no more than one condition per distinct category of
      condition. The number of different chronic conditions provides a simple measure
      of complexity, differing from measures of severity of illness that pertain to a
      particular episode of treatment. A multivariate regression finds that the number
      of chronic conditions is an independent influence on hospital cost per case,
      controlling for other key determinants. Patients with complex illness (e.g., 3+
      or 5+ chronic conditions) have a disproportionately large effect on hospital cost
      per year. The identification of patients in the hospital with complex illness can
      help in targeting new covered services in a health plan or in risk adjusting
      health plan premiums. Current policies and demonstrations for the Medicare
      program may not be sufficient to address complex illness.

PMID- 16651397
TI  - Nursing home consumer complaints and quality of care: a national view.
AB  - This study uses 5 years of national data on investigated nursing home complaints
      (1998-2002) to evaluate whether complaints might be used to assess nursing home
      quality of care. On-Line Survey Certification and Reporting (OSCAR) data are used
      to evaluate the association between consumer complaints, facility and resident
      characteristics, and other nursing home quality measures. The analyses are
      undertaken in the context of considerable cross-state variation in nursing home
      complaint processes and rates. Complaints varied across facility characteristics
      in ways consistent with the nursing home quality literature. Complaints were
      significantly positively associated with survey deficiencies and the presence of
      serious survey deficiencies, and significantly negatively associated with nurse
      and nurse aide staffing. Complaints performance was significantly predictive of
      survey deficiencies at subsequent inspections. This study presents the first
      national evidence for using consumer complaints to assess nursing home quality of
      care. Despite limitations, nursing home complaints appear to offer a real-time
      signal of quality concerns.

PMID- 16651398
TI  - Toward the creation of an institutional logic for the management of hospitals:
      efficiency in the early nineteen hundreds.
AB  - This research focuses on the creation of an institutional logic--efficiency--and
      on its organizing principles of standardization and business practices through a
      study of the American Hospital Association and its publication, the Modern
      Hospital. In the early years of the 20th century, efficiency began to emerge as a
      first institutional logic for the management of hospitals. The term was defined
      broadly, encompassing not only economy but also quality and breadth of services,
      as well as access to care. This early emphasis on efficiency foreshadowed three
      issues that affect health policy and hospital management to this day: the
      pressure on hospitals to introduce new technology while containing cost, the
      assumption that hospitals should act like businesses, and the practice of
      offering large hospitals as the model for other providers.

PMID- 16651399
TI  - Ethanol consumption enhances endothelin-1-induced contraction in the isolated rat
      carotid.
AB  - We investigated the mechanisms involved in the enhancement of endothelin (ET)-1
      vascular reactivity induced by ethanol consumption. Ethanol intake for 2, 6, and
      10 weeks enhanced the ET-1-induced contractile response of endothelium-intact but
      not endothelium-denuded rat carotid rings independently of the treatment
      duration. Conversely, phenylephrine-induced contraction was not affected by
      ethanol intake. The contraction induced by IRL1620 [succinyl-(Glu(9),Ala(11,15))
      ET-1-(8-21)], a selective ET(B) agonist, was increased after treatment with
      ethanol in endothelium-intact but not in endothelium-denuded carotid rings.
      Moreover, ET-1- and IRL1620-induced relaxation was reduced in endothelium-intact
      phenylephrine-precontracted rings from ethanol-treated rats. Acetylcholine
      induced relaxation was not affected by ethanol treatment. N(G)-Nitro-l-arginine
      methyl ester, 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one, indomethacin, and
      tetraethylammonium reduced the relaxation induced by IRL1620 in carotid glands
      from control but not ethanol-treated rats. The mRNA levels for ET(A) and ET(B)
      receptors were not altered by ethanol consumption. However, ethanol treatment
      reduced the protein expression of ET(B) receptors. Furthermore,
      immunohistochemical assays showed reduced immunostaining for endothelial ET(B)
      receptors after treatment with ethanol. We conclude that ethanol consumption
      enhances ET-1-induced contraction in the rat carotid and that this response is
      not different among the three periods of treatment used in this study. Finally,
      the potentiation of ET-1-induced vascular reactivity is probably caused by
      reduced expression of relaxing endothelial ET(B) receptors.

PMID- 16651400
TI  - Distinct functional characteristics of the lateral/basolateral amygdala GABAergic
      system in C57BL/6J and DBA/2J mice.
AB  - It is generally understood that genetic mechanisms contribute to pathological
      anxiety and that C57BL/6 (B6) and DBA/2J (D2) mice, inbred strains differing
      markedly in their anxiety-like behaviors, may represent a model system to study
      these contributions. Because lateral/basolateral amygdala (BLA) GABA(A) receptors
      help regulate anxiety-like behaviors, we have tested the hypothesis that
      differences in receptor function/expression may be related to strain-specific
      differences in experimentally measured anxiety. First, we demonstrated that
      anxiety-like behaviors in two separate assays were more substantial in D2 mice.
      Then, using whole-cell electrophysiology of isolated neurons, we found that D2
      BLA neurons expressed significantly greater GABA-gated responses than B6 BLA
      neurons. This was specific for GABA(A) receptors, because N-methyl-d-aspartate
      gated responses were similar between strains. At the molecular level, this
      increased GABA(A) function was associated with higher levels of alpha 2 subunit
      mRNA expression in D2 BLA. Finally, to understand the ramifications of these
      functional and molecular biological differences, we examined both electrically
      evoked GABAergic responses and spontaneous synaptic currents using whole-cell
      recordings with in vitro slice preparations. Presynaptic GABAergic function was
      more robust in D2 compared with B6 slices. Together, our findings suggest that
      genetic mechanisms differentially represented in these two inbred mouse strains
      lead to robust differences in pre- and postsynaptic aspects of amygdala GABAergic
      function.

PMID- 16651401
TI  - Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor
      highly expressed in gastrointestinal lymphocytes.
AB  - Here, the ligand binding, activation, and tissue distribution of the orphan G
      protein-coupled receptor (GPCR) GPR92 were studied. GPR92 binds and is activated
      by compounds based on the lysophosphatidic acid (LPA) backbone. The binding of
      LPA to GPR92 was of high affinity (K(D) = 6.4 +/- 0.9 nM) and led to an increase
      in both phosphoinositide hydrolysis and cAMP production. GPR92 is atypical in
      that it has a low sequence homology with the classic LPA(1-3) receptors (21-22%).
      Expression of GPR92 is mainly found in heart, placenta, spleen, brain, lung, and
      gut. Notably, GPR92 is highly expressed in the lymphocyte compartment of the
      gastrointestinal tract. It is the most abundant GPCR activated by LPA found in
      the small intestinal intraepithelial CD8+ cytotoxic T cells.

PMID- 16651402
TI  - Exploring a new twist on tumor metastasis.
AB  - Unraveling the genetic programs that drive -metastasis may offer insights into
      how to limit or prevent this deadly aspect of cancer progression. Our recent
      studies indicate that tumor cell metastasis involves the activity of the
      transcription factor, Twist, which regulates epithelial-mesenchymal transition
      and early embryonic morphogenesis. Here, we review the Twist signaling pathway
      during normal development and discuss how the transcription factor Twist and the
      epithelial-mesenchymal transition program impinge their biological functions
      during tumor metastasis.

PMID- 16651403
TI  - Normal stem cells and cancer stem cells: the niche matters.
AB  - Scientists have tried for decades to understand cancer development in the context
      of therapeutic strategies. The realization that cancers may rely on "cancer stem
      cells" that share the self-renewal feature of normal stem cells has changed the
      perspective with regard to new approaches for treating the disease. In this
      review, we propose that one of the differences between normal stem cells and
      cancer stem cells is their degree of dependence on the stem cell niche, a
      specialized microenvironment in which stem cells reside. The stem cell niche in
      adult somatic tissues plays an essential role in maintaining stem cells or
      preventing tumorigenesis by providing primarily inhibitory signals for both
      proliferation and differentiation. However, the niche also provides transient
      signals for stem cell division to support ongoing tissue regeneration. The
      balance between proliferation-inhibiting and proliferation-promoting signals is
      the key to homeostatic regulation of stem cell maintenance versus tissue
      regeneration. Loss of the niche can lead to loss of stem cells, indicating the
      reliance of stem cells on niche signals. Therefore, cancer stem cells may arise
      from an intrinsic mutation, leading to self-sufficient cell proliferation, and/or
      may also involve deregulation or alteration of the niche by dominant
      proliferation-promoting signals. Furthermore, the molecular machinery used by
      normal stem cells for homing to or mobilizing from the niche may be "hijacked" by
      cancer stem cells for invasion and metastasis. We hope this examination of the
      interaction between stem cells and their niche will enhance understanding of the
      process of cancer development, invasiveness, and metastasis and reveal possible
      targets for cancer treatment.

PMID- 16651404
TI  - Meeting report: exploiting the tumor microenvironment for therapeutics.
AB  - Recent progress in understanding the role of the tumor microenvironment in cancer
      progression was the subject of the 2nd International Tumor Metabolism Summit
      entitled "Exploiting the Tumor Microenvironment for Therapeutics," a meeting held
      at Palazzo Ducale in Genoa, Italy, October 7 to 8, 2005. One of the major
      conceptual advances in oncology over the last decade has been the appreciation
      that all major aspects of cancer biology are influenced by the tumor
      microenvironment. Two important means by which cancer cells adapt to their
      microenvironment are by reprogramming cellular glucose/energy metabolism to use
      pathways that generate ATP in the absence of O(2) and by stimulating angiogenesis
      to increase O(2) delivery. These responses are principally mediated at the
      transcriptional level by hypoxia-inducible factor-1. This meeting emphasized the
      complexity of the tumor microenvironment and opportunities for therapeutic
      intervention by targeting transcriptional and metabolic pathways that are
      activated during cancer progression. A better understanding of the crosstalk
      between signaling pathways and metabolic alterations that contribute to the
      cancer phenotype may provide insights leading to the development of novel
      therapeutic strategies.

PMID- 16651405
TI  - DNA damage-induced BARD1 phosphorylation is critical for the inhibition of
      messenger RNA processing by BRCA1/BARD1 complex.
AB  - BRCA1-associated RING domain protein BARD1, along with its heterodimeric partner
      BRCA1, plays important roles in cellular response to DNA damage. Immediate
      cellular response to genotoxic stress is mediated by a family of phosphoinositide
      3-kinase-related protein kinases, such as ataxia-telangiectasia mutated (ATM),
      ATM and Rad3-related, and DNA-dependent protein kinase. ATM-mediated
      phosphorylation of BRCA1 enhances the DNA damage checkpoint functions of BRCA1,
      but how BARD1 is regulated during DNA damage signaling has not been examined.
      Here, we report that BARD1 undergoes phosphorylation upon ionizing radiation or
      UV radiation and identify Thr(714) as the in vivo BARD1 phosphorylation site.
      Importantly, DNA damage functions of BARD1 (i.e., inhibition of pre-mRNA
      polyadenylation and degradation of RNA polymerase II) are abrogated in T714A and
      T734A mutants. Our findings suggest that phosphorylation of BARD1 is critical for
      the DNA damage functions of the BRCA1/BARD1 complex.

PMID- 16651406
TI  - Epigenetic inactivation of Betaig-h3 gene in human cancer cells.
AB  - Gene silencing by CpG island methylation in the promoter region is one of the
      mechanisms by which tumor suppressor genes are inactivated in human cancers. It
      has been shown previously that Betaig-h3 gene, which encodes an extracellular
      matrix protein involved in cell adhesion and tumorigenesis, is down-regulated or
      silenced in a variety of human cancer cell lines. To unravel the underlying
      molecular mechanism(s) for this phenomenon, DNA methylation patterns of Betaig-h3
      CpG island were examined in normal, immortalized, and cancer cell lines derived
      from lung, prostate, mammary, and kidney. A good correlation was observed between
      promoter hypermethylation and lost expression of Betaig-h3 gene, which was
      supported by the data that demethylation of promoter by 5-aza-2'-deoxycytidine
      reactivated Betaig-h3 and restored its expression in Betaig-h3-silenced tumor
      cell lines. This result was further substantiated by a luciferase reporter assay,
      showing the restoration of promoter activities and increased response to
      transforming growth factor-beta treatment in Betaig-h3-negative 293T cells when
      transfected with unmethylated Betaig-h3 promoter. In contrast, activity of Betaig
      h3 promoter was completely inactivated by in vitro methylation. Furthermore, CpG
      methylation of Betaig-h3 promoter was also shown in primary lung tumors that
      expressed decreased level of Betaig-h3 protein. These results suggest that
      promoter methylation plays a critical role in promoter silencing of the Betaig-h3
      gene in human tumor cells.

PMID- 16651407
TI  - Comparative genome analysis identifies the vitamin D receptor gene as a direct
      target of p53-mediated transcriptional activation.
AB  - p53 is the most frequently mutated tumor suppressor gene in human neoplasia and
      encodes a transcriptional coactivator. Identification of p53 target genes is
      therefore key to understanding the role of p53 in tumorigenesis. To identify
      novel p53 target genes, we first used a comparative genomics approach to identify
      p53 binding sequences conserved in the human and mouse genome. We hypothesized
      that potential p53 binding sequences that are conserved are more likely to be
      functional. Using stringent filtering procedures, 32 genes were newly identified
      as putative p53 targets, and their responsiveness to p53 in human cancer cells
      was confirmed by reverse transcription-PCR and real-time PCR. Among them, we
      focused on the vitamin D receptor (VDR) gene because vitamin D3 has recently been
      used for chemoprevention of human tumors. VDR is induced by p53 as well as
      several other p53 family members, and analysis of chromatin immunoprecipitation
      showed that p53 protein binds to conserved intronic sequences of the VDR gene in
      vivo. Introduction of VDR into cells resulted in induction of several genes known
      to be p53 targets and suppression of colorectal cancer cell growth. In addition,
      p53 induced VDR target genes in a vitamin D3-dependent manner. Our in silico
      approach is a powerful method for identification of functional p53 binding sites
      and p53 target genes that are conserved among humans and other organisms and for
      further understanding the function of p53 in tumorigenesis.

PMID- 16651408
TI  - Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through
      recruitment of histone deacetylase 1 by FG repeats.
AB  - The formation of fusion genes between NUP98 and members of the HOX family
      represents a critical factor for the genesis of acute leukemia or acute
      transformation of chronic myeloid leukemia (CML). To gain insights into the
      molecular mechanisms underlying the leukemogenesis of NUP98-HOX fusion products,
      we cloned NUP98-PMX1 from a CML-blast crisis patient with t(1;11) as a secondary
      chromosomal translocation, and functionally studied the fusion products in detail
      through various molecular and protein biochemical assays. In addition to many
      interesting features, we have found that the NUP98-PMX1 fusion protein exerts a
      repressive effect on PMX1 or serum response factor-mediated c-FOS activation,
      probably through the recruitment of a common corepressor histone deacetylase 1 by
      FG domains of the NUP98-PMX1 fusion protein. Moreover, we have provided evidence
      that the FG domains of NUP98-PMX1 and two other NUP98-containing fusion proteins,
      i.e., NUP98-HOXA9 and NUP98-HOXC11, all exhibit dual binding ability to both CREB
      binding protein, a coactivator, and histone deacetylase 1, a corepressor.
      Accordingly, we have hypothesized that this dual binding activity is shared by
      most, if not all, NUP98-HOX-involved fusion proteins, enabling these fusion
      proteins to act as both trans-activators and trans-repressors, and contributing
      to the genesis of acute leukemia or acute transformation of CML.

PMID- 16651409
TI  - Reversible kinetic analysis of Myc targets in vivo provides novel insights into
      Myc-mediated tumorigenesis.
AB  - Deregulated expression of the Myc transcription factor is a frequent causal
      mutation in human cancer. Thousands of putative Myc target genes have been
      identified in in vitro studies, indicating that Myc exerts highly pleiotropic
      effects within cells and tissues. However, the complexity and diversity of Myc
      gene targets has confounded attempts at identifying which of these genes are the
      critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of
      Myc in a reversibly switchable transgenic model of Myc-mediated beta cell
      tumorigenesis induces rapid tumor onset, whereas subsequent Myc deactivation
      triggers equally rapid tumor regression. Thus, sustained Myc activity is required
      for tumor maintenance. We have used this reversibly switchable kinetic tumor
      model in combination with high-density oligonucleotide microarrays to develop an
      unbiased strategy for identifying candidate Myc-regulated genes responsible for
      maintenance of Myc-dependent tumors. Consistent with known Myc functions, some
      Myc-regulated genes are involved in cell growth, cycle, and proliferation. In
      addition, however, many Myc-regulated genes are specific to beta cells,
      indicating that a significant component of Myc action is cell type specific.
      Finally, we identify a very restricted cadre of genes with expression that is
      inversely regulated upon Myc activation-induced tumor progression and
      deactivation-induced tumor regression. By definition, such genes are candidates
      for tumor maintenance functions. Combining reversibly switchable, transgenic
      models of tumor formation and regression with genomic profiling offers a novel
      strategy with which to deconvolute the complexities of oncogenic signaling
      pathways in vivo.

PMID- 16651410
TI  - Functional gene expression analysis uncovers phenotypic switch in aggressive
      uveal melanomas.
AB  - Microarray gene expression profiling is a powerful tool for generating molecular
      cancer classifications. However, elucidating biological insights from these large
      data sets has been challenging. Previously, we identified a gene expression-based
      classification of primary uveal melanomas that accurately predicts metastatic
      death. Class 1 tumors have a low risk and class 2 tumors a high risk for
      metastatic death. Here, we used genes that discriminate these tumor classes to
      identify biological correlates of the aggressive class 2 signature. A search for
      Gene Ontology categories enriched in our class-discriminating gene list revealed
      a global down-regulation of neural crest and melanocyte-specific genes and an up
      regulation of epithelial genes in class 2 tumors. Correspondingly, class 2 tumors
      exhibited epithelial features, such as polygonal cell morphology, up-regulation
      of the epithelial adhesion molecule E-cadherin, colocalization of E-cadherin and
      beta-catenin to the plasma membrane, and formation of cell-cell adhesions and
      acinar structures. One of our top class-discriminating genes was the helix-loop
      helix inhibitor ID2, which was strongly down-regulated in class 2 tumors. The
      class 2 phenotype could be recapitulated by eliminating Id2 in cultured class 1
      human uveal melanoma cells and in a mouse ocular melanoma model. Id2 seemed to
      suppress the epithelial-like class 2 phenotype by inhibiting an activator of the
      E-cadherin promoter. Consequently, Id2 loss triggered up-regulation of E
      cadherin, which in turn promoted anchorage-independent cell growth, a likely
      antecedent to metastasis. These findings reveal new roles for Id2 and E-cadherin
      in uveal melanoma progression, and they identify potential targets for
      therapeutic intervention.

PMID- 16651411
TI  - Chromatin modification of the trefoil factor 1 gene in human breast cancer cells
      by the Ras/mitogen-activated protein kinase pathway.
AB  - Histone H3 phosphorylation is a downstream response to activation of the
      Ras/mitogen-activated protein kinase (MAPK) pathway. This modification is thought
      to have a role in chromatin remodeling and in the initiation of gene
      transcription. In MCF-7 breast cancer cells, we observed that phosphorylated
      histone H3 (phospho-H3) at Ser(10) but not Ser(28) increased with phorbol ester
      (12-O-tetradecanoylphorbol-13-acetate, TPA) treatment. Although phosphorylated
      extracellular signal-regulated kinase 1/2 levels in these cells cultured under
      estradiol deplete and replete conditions displayed no change, a significant
      induction was observed after TPA treatment. Furthermore, whereas both estradiol
      and TPA increased trefoil factor 1 (TFF1) mRNA levels in these cells, only TPA
      induced and not estradiol-induced TFF1 expression was inhibited by the H3 kinase
      mitogen and stress activated protein kinase (MSK) inhibitor H89 and MAPK kinase
      inhibitor UO126, showing the involvement of the Ras/MAPK following TPA induction.
      Mutation of the activator protein 1 (AP-1) binding site abrogated the TPA-induced
      transcriptional response of the luciferase reporter gene under the control of the
      TFF1 promoter, showing the requirement for the AP-1 site. In chromatin
      immunoprecipitation assays, estradiol treatment resulted in the association of
      the estrogen receptor-alpha (ERalpha) and acetylated H3 with the TFF1 promoter.
      The levels of phospho-H3 and MSK1 associated with the TFF1 promoter were
      moderately increased. In the presence of TPA, whereas ERalpha was not bound to
      the promoter, a strong association of acetylated and/or phospho-H3, MSK1, and c
      Jun was observed. These results show that although both stimuli lead to TFF1 gene
      activation, estradiol and TPA exert their effects on TFF1 gene expression by
      different mechanisms.

PMID- 16651412
TI  - Frequent silencing of the candidate tumor suppressor PCDH20 by epigenetic
      mechanism in non-small-cell lung cancers.
AB  - Protocadherins are a major subfamily of the cadherin superfamily, but little is
      known about their functions and intracellular signal transduction. We identified
      a homozygous loss of protocadherin 20 (PCDH20, 13q21.2) in the course of a
      program to screen a panel of non-small-cell lung cancer (NSCLC) cell lines (1 of
      20 lines) for genomic copy number aberrations using an in-house array-based
      comparative genomic hybridization. PCDH20 mRNA was expressed in normal lung
      tissue but was not expressed in the majority of NSCLC cell lines without a
      homozygous deletion of this gene (10 of 19 lines, 52.6%). Expression of PCDH20
      mRNA was restored in gene-silenced NSCLC cells after treatment with 5-aza 2'
      deoxycytidine. The DNA methylation status of the PCDH20 CpG-rich region
      correlated inversely with the expression of the gene and a putative target region
      for methylation showed clear promoter activity in vitro. Methylation of this
      PCDH20 promoter was frequently observed in primary NSCLC tissues (32 of 59
      tumors, 54.2%). Among our primary NSCLC cases, the methylated PCDH20 seemed to be
      associated with a shorter overall survival (P = 0.0140 and 0.0211 in all and
      stage I tumors, respectively; log-rank test), and a multivariate analysis showed
      that the PCDH20 methylation status was an independent prognosticator. Moreover,
      restoration of PCDH20 expression in NSCLC cells reduced cell numbers in colony
      formation and anchorage-independent assays. These results suggest that epigenetic
      silencing by hypermethylation of the CpG-rich promoter region of PCDH20 leads to
      loss of PCDH20 function, which may be a factor in the carcinogenesis of NSCLC.

PMID- 16651413
TI  - Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota
      as a biomarker and potential oncogene in ovarian carcinoma.
AB  - The protein kinase C (PKC) family plays a key regulatory role in a wide range of
      cellular functions as well as in various cancer-associated signal transduction
      pathways. Here, we investigated the genomic alteration and gene expression of
      most known PKC family members in human ovarian cancer. The DNA copy number of PKC
      family genes was screened by a high-resolution array-based comparative genomic
      hybridization in 89 human ovarian cancer specimens. Five PKC genes exhibited
      significant DNA copy number gains, including PKCiota (43.8%), PKCbeta1 (37.1%),
      PKCgamma (27.6%), PKCzeta (22.5%), and PKCtheta (21.3%). None of the PKC genes
      exhibited copy number loss. The mRNA expression level of PKC genes was analyzed
      by microarray retrieval approach. Two of the amplified PKC genes, PKCiota and
      PKCtheta, were significantly up-regulated in ovarian cancer compared with normal
      ovary. Increased PKCiota expression correlated with tumor stage or grade, and
      PKCiota overexpression was seen mostly in ovarian carcinoma but not in other
      solid tumors. The above results were further validated by real-time reverse
      transcription-PCR with 54 ovarian cancer specimens and 24 cell lines;
      overexpression of PKCiota protein was also confirmed by tissue array and Western
      blot. Interestingly, overexpressed PKCiota did not affect ovarian cancer cell
      proliferation or apoptosis in vitro. However, decreased PKCiota expression
      significantly reduced anchorage-independent growth of ovarian cancer cells,
      whereas overexpression of PKCiota contributed to murine ovarian surface
      epithelium transformation in cooperation with mutant Ras. We propose that PKCiota
      may serve as an oncogene and a biomarker of aggressive disease in human ovarian
      cancer.

PMID- 16651414
TI  - Gene expression profiling shows medullary breast cancer is a subgroup of basal
      breast cancers.
AB  - Medullary breast cancer (MBC) is a rare but enigmatic pathologic type of breast
      cancer. Despite features of aggressiveness, MBC is associated with a favorable
      prognosis. Morphologic diagnosis remains difficult in many cases. Very little is
      known about the molecular alterations involved in MBC. Notably, it is not clear
      whether MBC and ductal breast cancer (DBC) represent molecularly distinct
      entities and what genes/proteins might account for their differences. Using whole
      genome oligonucleotide microarrays, we compared gene expression profiles of 22
      MBCs and 44 grade III DBCs. We show that MBCs are less heterogeneous than DBCs.
      Whereas different molecular subtypes (luminal A, luminal B, basal, ERBB2
      overexpressing, and normal-like) exist in DBCs, 95% MBCs display a basal profile,
      similar to that of basal DBCs. Supervised analysis identified gene expression
      signatures that discriminated MBCs from DBCs. Discriminator genes are associated
      with various cellular processes related to MBC features, in particular immune
      reaction and apoptosis. As compared with MBCs, basal DBCs overexpress genes
      involved in smooth muscle cell differentiation, suggesting that MBCs are a
      distinct subgroup of basal breast cancer with limited myoepithelial
      differentiation. Finally, MBCs overexpress a series of genes located on the 12p13
      and 6p21 chromosomal regions known to contain pluripotency genes. Our results
      contribute to a better understanding of MBC and of mammary oncogenesis in
      general.

PMID- 16651415
TI  - Dysregulated human myeloid nuclear differentiation antigen expression in
      myelodysplastic syndromes: evidence for a role in apoptosis.
AB  - Reduced levels of human myeloid nuclear differentiation antigen (MNDA) gene
      transcripts have been detected in both familial and sporadic cases of
      myelodysplastic syndromes (MDS). Numerous reports implicate elevated
      apoptosis/programmed cell death and death ligands and their receptors in the
      pathogenesis of MDS. MNDA and related proteins contain the pyrin domain that
      functions in signaling associated with programmed cell death and inflammation. We
      tested the hypothesis that MNDA is involved in the regulation of programmed cell
      death in human myeloid hematopoietic cells. Clones of K562 cells (MNDA-null) that
      expressed ectopic MNDA protein were established using retroviral transduction.
      MNDA-expressing K562 clones were resistant to tumor necrosis factor-related
      apoptosis inducing ligand (TRAIL)-induced apoptosis, but were not protected from
      programmed cell death induced with genotoxic agents or H(2)O(2). MNDA protein
      expression assessed in control and intermediate and high-grade MDS marrows showed
      several patterns of aberrant reduced MNDA. These variable patterns of
      dysregulated MNDA expression may relate to the variable pathophysiology of MDS.
      We propose that MNDA has a role regulating programmed cell death in myeloid
      progenitor cells, and that its down-regulation in MDS is related to granulocyte
      macrophage progenitor cell sensitivity to TRAIL-induced programmed cell death.

PMID- 16651416
TI  - The protease complex consisting of dipeptidyl peptidase IV and seprase plays a
      role in the migration and invasion of human endothelial cells in collagenous
      matrices.
AB  - Dipeptidyl peptidase IV (DPP4/CD26) and seprase/fibroblast activation protein
      alpha are homologous type II transmembrane, homodimeric glycoproteins that
      exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed
      in epithelial and endothelial cells and serves multiple functions in cleaving the
      penultimate positioned prolyl bonds at the NH(2) terminus of a variety of
      physiologically important peptides in the circulation. Recent studies showed a
      linkage between DPP4 and down-regulation of certain chemokines and mitogenic
      growth factors, and degradation of denatured collagens (gelatin), suggesting a
      role of DPP4 in the cell invasive phenotype. Here, we found the existence of a
      novel protease complex consisting of DPP4 and seprase in human endothelial cells
      that were activated to migrate and invade in the extracellular matrix in vitro.
      DPP4 and seprase were coexpressed with the three major protease systems (matrix
      metalloproteinase, plasminogen activator, and type II transmembrane serine
      protease) at the cell surface and organize as a complex at invadopodia-like
      protrusions. Both proteases were colocalized at the endothelial cells of
      capillaries, but not large blood vessels, in invasive breast ductal carcinoma in
      vivo. Importantly, monoclonal antibodies against the gelatin-binding domain of
      DPP4 blocked the local gelatin degradation by endothelial cells in the presence
      of the major metallo- and serine protease systems that modified pericellular
      collagenous matrices and subsequent cell migration and invasion. Thus, we have
      identified a novel mechanism involving the DPP4 gelatin-binding domain of the
      DPP4-seprase complex that facilitates the local degradation of the extracellular
      matrix and the invasion of the endothelial cells into collagenous matrices.

PMID- 16651417
TI  - Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and
      promotes proliferation of pancreatic carcinoma cells.
AB  - Pancreatic cancer is characterized by its invasiveness, early metastasis, and the
      production of large amounts of extracellular matrix (ECM). We analyzed the
      influence of type I collagen and fibronectin on the regulation of cellular
      adhesion in pancreatic cancer cell lines to characterize the role of ECM proteins
      in the development of pancreatic cancer. We show that collagen type I is able to
      initiate a disruption of the E-cadherin adhesion complex in pancreatic carcinoma
      cells. This is due to the increased tyrosine phosphorylation of the complex
      protein beta-catenin, which correlates with collagen type I-dependent activation
      of the focal adhesion kinase and its association with the E-cadherin complex. The
      activation and recruitment of focal adhesion kinase to the E-cadherin complex
      depends on the interaction of type I collagen with beta1-containing integrins and
      an integrin-mediated activation of the cellular kinase Src. The disassembly of
      the E-cadherin adhesion complex correlates with the nuclear translocation of beta
      catenin, which leads to an increasing expression of the beta-catenin-Lef/Tcf
      target genes, cyclin D1 and c-myc. In addition to that, cells grown on collagen
      type I show enhanced cell proliferation. We show that components of the ECM,
      produced by the tumor, contribute to invasiveness and metastasis by reducing E
      cadherin-mediated cell-cell adhesion and enhance proliferation in pancreatic
      tumor cells.

PMID- 16651418
TI  - p130Cas as a new regulator of mammary epithelial cell proliferation, survival,
      and HER2-neu oncogene-dependent breast tumorigenesis.
AB  - To investigate the mechanisms through which p130Cas adaptor protein is linked to
      tumorigenesis, we generated mouse mammary tumor virus (MMTV)-p130Cas mice
      overexpressing p130Cas in the mammary gland. MMTVp130Cas transgenic mice are
      characterized by extensive mammary epithelial hyperplasia during development and
      pregnancy and by delayed involution at the end of lactation. These phenotypes are
      associated with activation of Src kinase, extracellular signal-regulated kinase
      1/2, mitogen-activated protein kinase, and Akt pathways, leading to an increased
      rate of proliferation and a decreased apoptosis. A double-transgenic line derived
      from crossing MMTV-p130Cas with MMTV-HER2-Neu mice expressing the activated form
      of the HER2-Neu oncogene develops multifocal mammary tumors with a significantly
      shorter latency than the HER2-Neu parental strain alone. Mammary epithelial cells
      isolated from tumors of double-transgenic mice display increased tyrosine
      phosphorylation, c-Src, and Akt activation compared with cells derived from HER2
      Neu tumors. In addition, p130Cas down-regulation by RNA interference increases
      apoptosis in HER2-Neu-expressing cells, indicating that p130Cas regulates cell
      survival. Consistently with the double-transgenic mice model, p130Cas is
      overexpressed in a significant subset of human breast cancers and high levels of
      p130Cas in association with HER2 expression correlate with elevated
      proliferation. These findings provide evidences for a role of p130Cas as a
      positive regulator of both proliferation and survival in normal and transformed
      mammary epithelial cells. Its overexpression contributes to HER2-Neu-induced
      breast tumorigenesis, thus identifying this protein as a putative target for
      clinical therapy.

PMID- 16651419
TI  - Platelet-activating factor induces up-regulation of antiapoptotic factors in a
      melanoma cell line through nuclear factor-kappaB activation.
AB  - In this study, we investigated the influence of platelet-activating factor (PAF)
      on the induction of apoptosis-regulating factors in B16F10 melanoma cells. PAF
      increased the expression of mRNA and the protein synthesis of antiapoptotic
      factors, such as Bcl-2 and Bcl-xL, but did not increase the expression of the
      proapoptotic factor, Bax. A selective nuclear factor-kappaB (NF-kappaB)
      inhibitor, parthenolide, inhibited the effects of PAF. Furthermore, PAF inhibited
      etoposide-induced increases in caspase-3, caspase-8, and caspase-9 activities, as
      well as cell death. p50/p65 heterodimer increased the mRNA expression of Bcl-2
      and Bcl-xL and decreased etoposide-induced caspase activities and cell death. In
      an in vivo model in which Matrigel was injected s.c., PAF augmented the growth of
      B16F10 cells and attenuated etoposide-induced inhibition of B16F10 cells growth.
      These data indicate that PAF induces up-regulation of antiapoptotic factors in a
      NF-kappaB-dependent manner in a melanoma cell line, therefore suggesting that PAF
      may diminish the cytotoxic effect of chemotherapeutic agents.

PMID- 16651420
TI  - Dynamic imaging of emerging resistance during cancer therapy.
AB  - One of the greatest challenges in developing therapeutic regimens is the
      inability to rapidly and objectively assess tumor response due to treatment.
      Moreover, tumor response to therapeutic intervention in many cases is transient,
      and progressive alterations within the tumor may mask the effectiveness of an
      initially successful therapy. The ability to detect these changes as they occur
      would allow timely initiation of alternative approaches, maximizing therapeutic
      outcome. We investigated the ability of diffusion magnetic resonance imaging
      (MRI) to provide a sensitive measure of tumor response throughout the course of
      treatment, possibly identifying changes in sensitivity to the therapy. Orthotopic
      9L gliomas were subjected to two separate therapeutic regimens, with one group
      receiving a single 5-day cycle (1omega) of low-dose 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) and a second group receiving two cycles at the same dose,
      bisected with 2 days of rest (2omega). Apparent diffusion coefficient maps were
      acquired before and throughout treatment to observe changes in water mobility,
      and these observations were correlated to standard measures of therapeutic
      response and outcome. Our results showed that diffusion MRI was indeed able to
      detect the emergence of a drug-resistant tumor subpopulation subsequent to an
      initially successful cycle of BCNU therapy, leading to minimal gains from a
      second cycle. These diffusion MRI findings were highly correlated with tumor
      growth delay, animal survival, and ex vivo growth inhibition assays showing
      emerging resistance in excised tumors. Overall, this study highlights the ability
      of diffusion MRI to provide sensitive dynamic assessment of therapy-induced
      response, allowing early opportunities for optimization of therapeutic protocols.

PMID- 16651421
TI  - Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes
      apoptosis.
AB  - A variety of melanoma antigen A (MAGE-A) genes are commonly detected in non-small
      cell lung cancers. Their biological function is not well characterized but may
      involve the regulation of apoptosis and cell cycle progression. We hypothesized
      that MAGE-A4 is involved in the regulation of apoptosis. To investigate this,
      expression of MAGE-A was evaluated. MAGE-A4 was expressed in 48% of non-small
      cell lung carcinomas. Ninety percent of lung carcinomas expressing MAGE-A4 were
      classified as squamous cell carcinomas and 10% were adenocarcinomas. Tumor-free
      surrounding lung tissue was negative for MAGE-A4. A molecular clone of MAGE-A4
      derived from human lung cancer was stably expressed in human embryonic kidney
      cells (293 cells) to evaluate effects on cell death. Overexpression of MAGE-A4
      increased apoptosis as measured by the apoptotic index (P < 0.0001) and caspase-3
      activity (P < 0.002). Exposure to 25 micromol/L etoposide, a chemotherapeutic
      agent, increased the apoptotic effect (P < 0.0001). Furthermore, we show that
      MAGE-A4 silencing using a small interfering RNA approach results in decreased
      caspase-3 activity in the squamous cell lung cancer cell line H1703 by 58% (P =
      0.0027) and by 24% (P = 0.028) in 293/MAGE-A4 cells. These findings suggest that
      MAGE-A4 expression may promote tumor cell death, sensitize malignancies to
      apoptotic stimuli, such as chemotherapeutic agents, and therefore may represent a
      tumor suppressor protein.

PMID- 16651422
TI  - Noninvasive bioluminescence imaging of normal and spontaneously transformed
      prostate tissue in mice.
AB  - Several transgenic mouse models of prostate cancer have been developed recently
      that are able to recapitulate many key biological features of the human
      condition. It would, therefore, be desirable to employ these models to test the
      efficacy of new therapeutics before clinical trial; however, the variable onset
      and non-visible nature of prostate tumor development limit their use for such
      applications. We now report the generation of a transgenic reporter mouse that
      should obviate these limitations by enabling noninvasive in vivo bioluminescence
      imaging of normal and spontaneously transformed prostate tissue in the mouse. We
      used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to
      achieve specific and robust expression of firefly luciferase in the prostate
      glands of transgenic mice. Ex vivo bioluminescence imaging and in situ
      hybridization analysis confirmed that luciferase expression was restricted to the
      epithelium in all four lobes of the prostate. We also show that PSA-Luc mice
      exhibit decreased but readily detectable levels of in vivo bioluminescence over
      extended time periods following androgen ablation. These results suggest that
      this reporter should enable in vivo imaging of both androgen-dependent and
      androgen-independent prostate tumor models. As proof-of-principle, we show that
      we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in
      mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can
      be successfully used to image tumor response to androgen ablation in transgenic
      mice and, as a result, that we can rapidly identify individual animals capable of
      sustaining tumor growth in the absence of androgen.

PMID- 16651423
TI  - The interaction mode of premalignant Schwann and immune effector cells during
      chemically induced carcinogenesis in the rat peripheral nervous system is
      strongly influenced by genetic background.
AB  - Contrary to rats of the highly sensitive inbred strain BDIX, BDIV rats are
      resistant to the induction of malignant schwannomas by N-ethyl-N-nitrosourea,
      arising predominantly in the trigeminal nerves. A point mutation of the neu/erbB
      2 gene diagnostic of N-ethyl-N-nitrosourea-induced rat schwannomas is an early
      marker of Schwann precursor cells at high risk of subsequent malignant
      transformation. Neu-mutant cells initially arise at a similar frequency in
      sensitive and resistant animals. However, these cells disappear from the
      trigeminal nerves of resistant rats while giving rise to highly malignant
      schwannomas in susceptible animals. The resistance of BDIV rats obviously
      includes mechanisms to recognize and eliminate premalignant cells. The
      involvement of a cellular immune response was investigated in trigeminal nerves
      of both strains at different times after neonatal carcinogen exposure. An
      inflammatory reaction involving sequentially CD4(+) macrophages and T helper
      cells, CD8(+) cytotoxic T cells, and ED1(+) and ED2(+) macrophages was detected
      as a consequence of N-ethyl-N-nitrosourea treatment as early as postnatal day 40,
      briefly after the emergence of premalignant neu-mutant Schwann cells. It
      persisted throughout the observation period (40-250 days). However, there were no
      gross differences in immune cell counts between tumor-susceptible and tumor
      resistant rats, except for a moderate increase of ED2(+) macrophages in N-ethyl-N
      nitrosourea-treated BDIX rats only. Differential interactions of immune effector
      cells with premalignant Schwann cells may thus be involved in genetically
      determined tumor susceptibility or resistance, which could include functional
      differences of immune effector cells and/or a differential capability of
      premalignant Schwann cells to escape or counteract the cellular immune response.

PMID- 16651424
TI  - Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent
      inhibition of p53.
AB  - Notch signaling is believed to promote cell survival in general. However, the
      mechanism is not clearly understood. Here, we show that cells expressing
      intracellular domain of human Notch1 (NIC-1) are chemoresistant in a wild-type
      p53-dependent manner. NIC-1 inhibited p53 by inhibiting its activating
      phosphorylations at Ser(15), Ser(20), and Ser(392) as well as nuclear
      localization. In addition, we found that inhibition of p53 by NIC-1 mainly occurs
      through mammalian target of rapamycin (mTOR) using phosphatidylinositol 3-kinase
      (PI3K)-Akt/protein kinase B (PKB) pathway as the mTOR inhibitor, rapamycin
      treatment abrogated NIC-1 inhibition of p53 and reversed the chemoresistance.
      Consistent with this, rapamycin failed to reverse NIC-1-induced chemoresistance
      in cells expressing rapamycin-resistant mTOR. Further, ectopic expression of
      eukaryotic initiation factor 4E (eIF4E), a translational regulator that acts
      downstream of mTOR, inhibited p53-induced apoptosis and conferred protection
      against p53-mediated cytotoxicity to similar extent as that of NIC-1
      overexpression but was not reversed by rapamycin, which indicates that eIF4E is
      the major target of mTOR in Notch1-mediated survival signaling. Finally, we show
      that MCF7 (breast cancer) and MOLT4 (T-cell acute lymphoblastic leukemia) cells
      having aberrant Notch1 signaling are chemoresistant, which can be reversed by
      both PI3K and mTOR inhibitors. These results establish that Notch1 signaling
      confers chemoresistance by inhibiting p53 pathway through mTOR-dependent PI3K
      Akt/PKB pathway and imply that p53 status perhaps is an important determinant in
      combination therapeutic strategies, which use mTOR inhibitors and chemotherapy.

PMID- 16651425
TI  - Distinct roles of nonmuscle myosin II isoforms in the regulation of MDA-MB-231
      breast cancer cell spreading and migration.
AB  - Initial stages of tumor cell metastasis involve an epithelial-mesenchyme
      transition that involves activation of amoeboid migration and loss of cell-cell
      adhesion. The actomyosin cytoskeleton has fundamental but poorly understood roles
      in these events. Myosin II, an abundant force-producing protein, has roles in
      cell body translocation and retraction of the posterior of the cell during
      migration. Recent studies have suggested that this protein may also have roles in
      leading edge protrusive events. The metastasis-promoting protein metastasin-1, a
      regulator of myosin II assembly, colocalizes with myosin IIA at the leading edge
      of cancer cells, suggesting direct roles for myosin II in metastatic behavior. We
      have assessed the roles of specific myosin II isoforms during lamellar spreading
      of MDA-MB-231 breast cancer cells on extracellular matrix. We find that the two
      major myosin II isoforms IIA and IIB are both expressed in these cells, and both
      are recruited dramatically to the lamellar margin during active spreading on
      fibronectin. There is also a transient increase in regulatory light chain
      phosphorylation that correlates the recruitment of myosin IIA and myosin IIB into
      this spreading margin. Pharmacologic inhibition of myosin II or myosin light
      chain kinase dramatically reduced spreading. Depletion of myosin IIA via small
      interfering RNA impaired migration but enhanced lamellar spreading, whereas
      depletion of myosin IIB impaired not only migration but also impaired initial
      rates of lamellar spreading. These results indicate that both isoforms are
      critical for the mechanics of cell migration, with myosin IIB seeming to have a
      preferential role in the mechanics of lamellar protrusion.

PMID- 16651426
TI  - beta-Catenin/Wnt signaling regulates expression of the membrane type 3 matrix
      metalloproteinase in gastric cancer.
AB  - Activation of Wnt signaling through beta-catenin dysregulation occurs in numerous
      human tumors, including gastric cancer. The specific consequences of Wnt
      signaling in gastric cancer, however, are not well characterized. This study
      shows that the introduction of mutant beta-catenin into gastric cancer cell lines
      by adenoviral infection enhances invasiveness and proliferation and up-regulates
      the expression of the gene encoding the matrix metalloproteinase (MMP) family
      member membrane type 3 MMP (MT3-MMP). Up-regulation of MT3-MMP is critical to the
      invasive phenotype as shown by small interfering RNA (siRNA) studies.
      Immunohistochemical staining also showed that MT3-MMP was highly expressed in
      gastric cancers with activating beta-catenin mutations. These observations
      suggest that Wnt activation may contribute to gastric cancer progression by
      increasing the invasiveness of neoplastic cells in the stomach via up-regulation
      of MT3-MMP expression.

PMID- 16651427
TI  - Validation of met as a therapeutic target in alveolar and embryonal
      rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a highly malignant soft-tissue tumor of childhood
      deriving from skeletal muscle cells. RMS can be classified in two major
      histologic subtypes: embryonal (ERMS) and alveolar (ARMS), the latter being
      characterized by the PAX3/7-FKHR translocation. Here we first investigated
      whether the Met receptor, a transcriptional target of PAX3 and PAX7, has a role
      in PAX3-FKHR-mediated transformation. Following PAX3-FKHR transduction, Met was
      up-regulated in mouse embryonal fibroblasts (MEF), NIH 3T3 and C2C12 cells, and
      they all acquired anchorage independence. This property was lost in low serum but
      addition of hepatocyte growth factor/scatter factor (HGF/SF) rescued soft-agar
      growth. Genetic proof that Met is necessary for this PAX3-FKHR-mediated effect
      was obtained by transducing with PAX3-FKHR MEFs derived from Met mutant
      (Met(D/D)) and wild-type (Met(+/+)) embryos. Only Met(+/+) MEFs acquired
      anchorage-independent growth whereas PAX3-FKHR-transduced Met(D/D) cells were
      unable to form colonies in soft agar. To verify if Met had a role in RMS
      maintenance, we silenced the receptor by transducing ERMS and ARMS cell lines
      with an inducible lentivirus expressing an anti-Met short hairpin RNA (shRNA).
      Met down-regulation significantly affected RMS cells proliferation, survival,
      invasiveness, and anchorage-independent growth. Finally, induction of the Met
      directed shRNA promoted a dramatic reduction of tumor mass in a xenograft model
      of RMS. Our data show that both ARMS- and ERMS-derived cell lines, in spite of
      the genetic drift which may have occurred in years of culture, seem to have
      retained an "addiction" to the Met oncogene and suggest that Met may represent a
      target of choice to develop novel therapeutic strategies for ARMS.

PMID- 16651428
TI  - MET overexpression turns human primary osteoblasts into osteosarcomas.
AB  - The MET oncogene was causally involved in the pathogenesis of a rare tumor, i.e.,
      the papillary renal cell carcinoma, in which activating mutations, either
      germline or somatic, were identified. MET activating mutations are rarely found
      in other human tumors, whereas at higher frequencies, MET is amplified and/or
      overexpressed in sporadic tumors of specific histotypes, including osteosarcoma.
      In this work, we provide experimental evidence that overexpression of the MET
      oncogene causes and sustains the full-blown transformation of osteoblasts.
      Overexpression of MET, obtained by lentiviral vector-mediated gene transfer,
      resulted in the conversion of primary human osteoblasts into osteosarcoma cells,
      displaying the transformed phenotype in vitro and the distinguishing features of
      human osteosarcomas in vivo. These included atypical nuclei, aberrant mitoses,
      production of alkaline phosphatase, secretion of osteoid extracellular matrix,
      and striking neovascularization. Although with a lower tumorigenicity, this
      phenotype was superimposable to that observed after transfer of the MET gene
      activated by mutation. Both transformation and tumorigenesis were fully abrogated
      when MET expression was quenched by short-hairpin RNA or when signaling was
      impaired by a dominant-negative MET receptor. These data show that MET
      overexpression is oncogenic and that it is essential for the maintenance of the
      cancer phenotype.

PMID- 16651429
TI  - Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a
      potent proteasome inhibitor and suppresses human prostate cancer growth in nude
      mice.
AB  - Interest in the use of traditional medicines for cancer prevention and treatment
      is increasing. In vitro, in vivo, and clinical studies suggest the potential use
      of proteasome inhibitors as novel anticancer drugs. Celastrol, an active compound
      extracted from the root bark of the Chinese medicine "Thunder of God Vine"
      (Tripterygium wilfordii Hook F.), was used for years as a natural remedy for
      inflammatory conditions. Although Celastrol has been shown to induce leukemia
      cell apoptosis, the molecular target involved has not been identified.
      Furthermore, whether Celastrol has antitumor activity in vivo has never been
      conclusively shown. Here, we report, for the first time, that Celastrol potently
      and preferentially inhibits the chymotrypsin-like activity of a purified 20S
      proteasome (IC(50) = 2.5 micromol/L) and human prostate cancer cellular 26S
      proteasome (at 1-5 micromol/L). Inhibition of the proteasome activity by
      Celastrol in PC-3 (androgen receptor- or AR-negative) or LNCaP (AR-positive)
      cells results in the accumulation of ubiquitinated proteins and three natural
      proteasome substrates (IkappaB-alpha, Bax, and p27), accompanied by suppression
      of AR protein expression (in LNCaP cells) and induction of apoptosis. Treatment
      of PC-3 tumor-bearing nude mice with Celastrol (1-3 mg/kg/d, i.p., 1-31 days)
      resulted in significant inhibition (65-93%) of the tumor growth. Multiple assays
      using the animal tumor tissue samples from both early and end time points showed
      in vivo inhibition of the proteasomal activity and induction of apoptosis after
      Celastrol treatment. Our results show that Celastrol is a natural proteasome
      inhibitor that has a great potential for cancer prevention and treatment.

PMID- 16651430
TI  - Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver
      damage in hepatocellular carcinoma progression.
AB  - Hepatocellular carcinoma is among the most common and lethal cancers in humans.
      Hepatocellular carcinoma is commonly associated with physical or functional
      inactivation of the p53 tumor suppressor, high levels of chromosomal instability,
      and disease conditions causing chronic cycles of hepatocyte death and
      regeneration. Mounting evidence has implicated regeneration-induced telomere
      erosion as a potential mechanism fueling genome instability. In mouse models of
      hepatocellular carcinoma, telomere dysfunction has been shown to enhance
      initiation of hepatic neoplasias yet constrain full malignant progression of
      these neoplasms possibly due to activation of a p53-dependent checkpoint and/or
      intolerable levels of genomic instability. Here, in a hepatocellular carcinoma
      prone model brought about through toxin-induced hepatocyte injury and
      regeneration, we sought to determine the cooperative interactions of germ line
      p53 mutation and telomere dysfunction [produced by telomerase reverse
      transcriptase (mTERT) gene knockout]. In the setting of intact telomeres, p53
      mutation had no effect on hepatocarcinogenesis, whereas in the setting of
      telomere dysfunction, p53 mutation enabled advanced hepatocellular carcinoma
      disease. Notably, there was no evidence of deletion or mutation of the wild-type
      p53 allele in the late generation mTert(-/-)p53(+/-) mice, suggesting that
      reduced levels of p53 potently enable hepatocellular carcinoma progression in the
      setting of telomere dysfunction. Thus, this study supports a model that, in the
      face of chronic liver damage, attenuated p53 function and telomere-induced
      chromosomal instability play critical and cooperative roles in the progression of
      hepatocellular carcinoma.

PMID- 16651431
TI  - Splicing factor Tra2-beta1 is specifically induced in breast cancer and regulates
      alternative splicing of the CD44 gene.
AB  - The human CD44 gene undergoes extensive alternative splicing of multiple variable
      exons positioned in a cassette in the middle of the gene. Expression of
      alternative exons is often restricted to certain tissues and could be associated
      with tumor progression and metastasis of several human malignancies, including
      breast cancer. Exon v4 contains multiple copies of a C/A-rich exon enhancer
      sequence required for optimal inclusion of the exon and binding to the nucleic
      acid-binding proteins YB-1 and human Tra2-beta1. Here, we show that hTra2-beta1,
      a member of the extended family of serine/arginine-rich (SR) splicing factors,
      enhances the in vivo inclusion of CD44 exons v4 and v5. It increased inclusion of
      exons v4 and v5 and acted synergistically with YB-1. Activation required the C/A
      rich enhancer within exon v4. Several other SR proteins had none or only a slight
      effect on CD44 exon inclusion. In contrast, SC35 inhibited exon usage and
      antagonized the effects of Tra2 or YB-1. In a matched pair analysis of human
      breast cancers and their corresponding nonpathologic tissue controls, we found a
      significant induction of Tra2-beta1 in invasive breast cancer, both on the RNA
      and protein levels. Together with our functional data, these results suggest an
      important role for Tra2-beta1 in breast cancer. Induction of this splicing factor
      might be responsible for splicing of CD44 isoforms associated with tumor
      progression and metastasis.

PMID- 16651432
TI  - Inhibition of the phosphatidylinositol 3'-kinase pathway promotes autocrine Fas
      induced death of phosphatase and tensin homologue-deficient prostate cancer
      cells.
AB  - Rationally designed therapeutics that target the phosphatidylinositol 3'-kinase
      (PI3K) cell survival pathway are currently in preclinical and clinical
      development for cancer therapy. Drugs targeting the PI3K pathway aim to inhibit
      proliferation, promote apoptosis, and enhance chemosensitivity and
      radiosensitivity of cancer cells. The phosphatase and tensin homologue (PTEN)
      phosphatidylinositol 3'-phosphatase is a key negative regulator of the PI3K
      pathway. Inactivation of the PTEN tumor suppressor results in constitutive
      activation of the PI3K pathway and is found in approximately 50% of advanced
      prostate cancers, which correlates with a high Gleason score and poor prognosis.
      Inhibition of the PI3K pathway leads to apoptosis of prostate cancer cells;
      however, the precise mechanism by which this occurs is unknown. Here we report
      that apoptotic cell death of PTEN-deficient LNCaP and PC3 prostate cancer cells
      induced by the PI3K inhibitor LY294002 can be abrogated by disrupting Fas/Fas
      ligand (FasL) interactions with recombinant Fas:Fc fusion protein or FasL
      neutralizing antibody (Nok-1), or by expressing dominant-negative Fas-associated
      death domain. Furthermore, we find that apoptosis induced by expression of wild
      type PTEN, driven by a tetracycline-inducible expression system in LNCaP cells,
      can be inhibited by blocking Fas/FasL interaction using Fas:Fc or Nok-1. These
      data show that apoptosis induced by blockade of the PI3K pathway in prostate
      tumor cells is mediated by an autocrine Fas/FasL apoptotic mechanism and the Fas
      apoptotic pathway is both necessary and sufficient to mediate apoptosis by PI3K
      inhibition.

PMID- 16651433
TI  - Estradiol and tamoxifen regulate endostatin generation via matrix
      metalloproteinase activity in breast cancer in vivo.
AB  - Matrix metalloproteinases (MMP) are important regulators of tumor progression and
      angiogenesis. MMPs generate both proangiogenic and antiangiogenic fragments, such
      as vascular endothelial growth factor and endostatin. The in vivo activation of
      MMPs and endostatin generation occur mainly in the extracellular environment by
      interactions of different cell types. Therefore, these processes are necessary to
      study in the extracellular space in vivo. Sex steroids play a dominant role in
      breast carcinogenesis, by largely unknown mechanisms. In the present study, we
      used in vivo microdialysis to directly quantify MMP-2 and MMP-9 activity and
      sample endostatin from both stroma (murine) and tumor (human) cells in vivo in
      solid MCF-7 tumors in nude mice. We found that tamoxifen in combination with
      estradiol increased tumor MMP-2/MMP-9 in vivo activity, endostatin levels, and
      decreased tumor vascularization compared with estradiol treatment only. The
      stroma-derived endostatin was three to five times higher than cancer cell
      generated endostatin. After inhibition of MMP-2/MMP-9, endostatin levels
      decreased, providing evidence that these proteases are highly involved in the
      generation of endostatin. Our results support the previously reported concept
      that MMPs may serve as negative regulators of angiogenesis. The regulation of
      endostatin generation by modulation of MMP-2/MMP-9 activities suggests a
      previously unrecognized mechanism of estradiol and tamoxifen, which may have
      implications for the pathogenesis of breast cancer.

PMID- 16651434
TI  - The regulation of exosome secretion: a novel function of the p53 protein.
AB  - The p53 protein responds to stress signals by regulating the transcription of a
      variety of genes. Some of these genes encode secreted proteins that may be
      involved in the communication between adjacent cells. In this study, a proteomics
      approach was employed to identify proteins secreted by cells in a p53-dependent
      manner after DNA damage. In addition to the known transcriptional targets of p53,
      a set of proteins encoded by genes that are not transcriptional targets of p53
      were found to increase in the culture medium after p53 activation. These proteins
      exit the cell via small, secreted vesicles called exosomes and exosome production
      by cells was found to be regulated by the p53 response. A p53-regulated gene
      product, TSAP6, was shown to enhance exosome production in cells undergoing a p53
      response to stress. Thus, the p53 pathway regulates the production of exosomes
      into the medium and these vesicles can communicate with adjacent cells and even
      cells of the immune system.

PMID- 16651435
TI  - Gefitinib modulates the function of multiple ATP-binding cassette transporters in
      vivo.
AB  - The 4-anilinoquinazoline (4-AQ) derivative gefitinib (Iressa) is an oral
      epidermal growth factor receptor tyrosine kinase inhibitor. Oral administration
      of 4-AQ molecules, such as gefitinib, inhibits ATP-binding cassette (ABC)
      transporter-mediated drug efflux and strongly increases the apparent
      bioavailability of coadministered drug molecules that are transporter substrates.
      Based on in vitro studies investigating 4-AQ interactions with several
      transporters, these effects have primarily been attributed to the inhibition of
      breast cancer resistance protein (BCRP; ABCG2). Although 4-AQ shows in vitro
      inhibition of P-glycoprotein [multidrug resistance protein (MDR1); ABCB1], the in
      vivo effect on this and other transporters is not known. In our studies,
      pretreatment of Abcg2(-/-) and Mdr1(a/b)(-/-) mice with gefitinib increased oral
      absorption and decreased systemic clearance of topotecan, a model substrate,
      indicating that additional transporters were inhibited. These results were
      extended to human orthologues using engineered cell lines to show that gefitinib
      inhibited the efflux of BCRP and MDR1 substrates and restored vincristine
      sensitivity in MDR1-expressing cells. Although gefitinib inhibited BCRP more
      potently than MDR1 (10-fold), the inhibition of both transporters occurred at
      clinically relevant concentrations (e.g., 1-5 micromol/L). These studies
      illustrate the broad implications for the therapeutic combination of gefitinib or
      other 4-AQ molecules with agents that are BCRP and MDR1 substrates. 4-AQ
      molecules may offer a means to increase the low and variable oral drug absorption
      of transporter substrates while decreasing interpatient variability and reversing
      tumor drug resistance.

PMID- 16651436
TI  - Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to
      circumvent multidrug resistance in cancer.
AB  - ATP-binding cassette (ABC) proteins include the best known mediators of
      resistance to anticancer drugs. In particular, ABCB1 [MDR1/P-glycoprotein (P-gp)]
      extrudes many types of drugs from cancer cells, thereby conferring resistance to
      those agents. Attempts to overcome P-gp-mediated drug resistance using specific
      inhibitors of P-gp has had limited success and has faced many therapeutic
      challenges. As an alternative approach to using P-gp inhibitors, we characterize
      a thiosemicarbazone derivative (NSC73306) identified in a generic screen as a
      compound that exploits, rather than suppresses, P-gp function to induce
      cytotoxicity. Cytotoxic activity of NSC73306 was evaluated in vitro using human
      epidermoid, ovarian, and colon cancer cell lines expressing various levels of P
      gp. Our findings suggest that cells become hypersensitive to NSC73306 in
      proportion to the increased P-gp function and multidrug resistance (MDR).
      Abrogation of both sensitivity to NSC73306 and resistance to P-gp substrate
      anticancer agents occurred with specific inhibition of P-gp function using either
      a P-gp inhibitor (PSC833, XR9576) or RNA interference, suggesting that
      cytotoxicity was linked to MDR1 function, not to other, nonspecific factors
      arising during the generation of resistant or transfected cells. Molecular
      characterization of cells selected for resistance to NSC73306 revealed loss of P
      gp expression and consequent loss of the MDR phenotype. Although hypersensitivity
      to NSC73306 required functional expression of P-gp, biochemical assays revealed
      no direct interaction between NSC73306 and P-gp. This article shows that NSC73306
      kills cells with intrinsic or acquired P-gp-induced MDR and indirectly acts to
      eliminate resistance to MDR1 substrates.

PMID- 16651437
TI  - Antitumor and antimetastatic activities of docetaxel are enhanced by genistein
      through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB
      (RANK)/RANK ligand/MMP-9 signaling in prostate cancer.
AB  - Bone metastasis is very common in advanced prostate cancer. Docetaxel has been
      shown to improve survival in patients with metastatic prostate cancer. However,
      treatment with docetaxel is associated with a certain degree of toxicity.
      Genistein, derived from soybeans, has been found to inhibit cancer cell growth
      without toxicity. We have recently reported that genistein could potentiate the
      antitumor activity of chemotherapeutic agents both in vitro and in vivo. However,
      the molecular mechanism of this novel effect of genistein has not been fully
      elucidated. In this study, we found that genistein significantly potentiated the
      antitumor, anti-invasive, and antimetastatic activities of docetaxel both in
      culture and in severe combined immunodeficient (SCID)-human model of experimental
      prostate cancer bone metastasis. We further conducted microarray analysis, real
      time reverse transcription-PCR, Western blot analysis, small interfering RNA and
      cDNA transfection, matrix metalloproteinase-9 (MMP-9) activity assay, and
      invasion assay. We found that the expression of osteoprotegerin (OPG) was induced
      by genistein and inhibited by docetaxel, whereas genistein significantly down
      regulated the expression and secretion of receptor activator of nuclear factor
      kappaB (RANK) ligand (RANKL) and inhibited osteoclast formation. Moreover,
      genistein down-regulated the expression and activity of MMP-9, which was induced
      by docetaxel treatment, and inhibited invasion of PC-3 cells. These results
      suggest that the observed potentiation of antitumor activity of docetaxel by
      genistein in the SCID-human model of experimental bone metastasis could be
      mediated by regulation of OPG/RANK/RANKL/MMP-9 signaling, resulting in the
      inhibition of osteoclastic bone resorption and prostate cancer bone metastasis.
      From these results, we conclude that genistein could be a promising nontoxic
      agent to improve the treatment outcome of metastatic prostate cancer with
      docetaxel.

PMID- 16651438
TI  - Luteolin promotes degradation in signal transducer and activator of transcription
      3 in human hepatoma cells: an implication for the antitumor potential of
      flavonoids.
AB  - In this study, we have investigated the underlying molecular mechanism for the
      potent proapoptotic effect of luteolin on human hepatoma cells both in vitro and
      in vivo, focusing on the signal transducer and activator of transcription 3
      (STAT3)/Fas signaling. A clear apoptosis was found in the luteolin-treated HLF
      hepatoma cells in a time- and dosage-dependent manner. In concert with the
      caspase-8 activation by luteolin, an enhanced expression in functional Fas/CD95
      was identified. Consistent with the increased Fas/CD95 expression, a drastic
      decrease in the Tyr(705) phosphorylation of STAT3, a known negative regulator of
      Fas/CD95 transcription, was found within 20 minutes in the luteolin-treated
      cells, leading to down-regulation in the target gene products of STAT3, such as
      cyclin D1, survivin, Bcl-xL, and vascular endothelial growth factor. Of interest,
      the rapid down-regulation in STAT3 was consistent with an accelerated ubiquitin
      dependent degradation in the Tyr(705)-phosphorylated STAT3, but not the Ser(727)
      phosphorylated one, another regulator of STAT3 activity. The expression level of
      Ser(727)-phosphorylated STAT3 was gradually decreased by the luteolin treatment,
      followed by a fast and clear down-regulation in the active forms of CDK5, which
      can phosphorylate STAT3 at Ser(727). An overexpression in STAT3 led to resistance
      to luteolin, suggesting that STAT3 was a critical target of luteolin. In nude
      mice with xenografted tumors using HAK-1B hepatoma cells, luteolin significantly
      inhibited the growth of the tumors in a dosage-dependent manner. These data
      suggested that luteolin targeted STAT3 through dual pathways-the ubiquitin
      dependent degradation in Tyr(705)-phosphorylated STAT3 and the gradual down
      regulation in Ser(727)-phosphorylated STAT3 through inactivation of CDK5, thereby
      triggering apoptosis via up-regulation in Fas/CD95.

PMID- 16651439
TI  - Combination of a fusogenic glycoprotein, prodrug activation, and oncolytic herpes
      simplex virus for enhanced local tumor control.
AB  - We have previously developed an oncolytic herpes simplex virus-1 based on a
      clinical virus isolate, which was deleted for ICP34.5 to provide tumor selected
      replication and ICP47 to increase antigen presentation as well as tumor selective
      virus replication. A phase I/II clinical trial using a version of this virus
      expressing granulocyte macrophage colony-stimulating factor has shown promising
      results. The work reported here aimed to develop a version of this virus in which
      local tumor control was further increased through the combined expression of a
      highly potent prodrug activating gene [yeast cytosine deaminase/uracil phospho
      ribosyltransferase fusion (Fcy::Fur)] and the fusogenic glycoprotein from gibbon
      ape leukemia virus (GALV), which it was hoped would aid the spread of the
      activated prodrug through the tumor. Viruses expressing the two genes
      individually or in combination were constructed and tested, showing (a) GALV
      and/or Fcy::Fur expression did not affect virus growth; (b) GALV expression
      causes cell fusion and increases the tumor cell killing at least 30-fold in vitro
      and tumor shrinkage 5- to 10-fold in vivo; (c) additional expression of Fcy::Fur
      combined with 5-fluorocytosine administration improves tumor shrinkage further.
      These results indicate, therefore, that the combined expression of the GALV
      protein and Fcy::Fur provides a highly potent oncolytic virus with improved
      capabilities for local tumor control. It is intended to enter the GALV/Fcy::Fur
      expressing virus into clinical development for the treatment of tumor types, such
      as pancreatic or lung cancer, where local control would be anticipated to be
      clinically advantageous.

PMID- 16651440
TI  - IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces
      nonobese diabetic/severe combined immunodeficient engraftment of some acute
      lymphoblastic leukemia cell lines and primary leukemic samples.
AB  - The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of
      patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is
      expressed at extremely high levels in ALL patients with mixed lineage leukemia
      rearrangements or hyperdiploidy and is sometimes mutated in these same patients.
      In this report, we investigate the effects of treating ALL cell lines and primary
      samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing
      binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3
      mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in
      ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation
      was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10
      actually stimulated FLT3 activation, possibly as a result of antibody-mediated
      receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity,
      such an antibody could still prove efficacious against leukemia cells in vivo. In
      fact, IMC-EB10 treatment significantly prolonged survival and/or reduced
      engraftment of several ALL cell lines and primary ALL samples in nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when
      IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence
      activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice
      surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy
      reduced leukemic engraftment below the level of detection in these assays
      (<0.001%). Furthermore, in vivo IMC-EB10 treatment did not select for resistant
      cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10
      cytotoxicity upon retransplantation. In vivo studies involving either partial
      depletion or activation of natural killer (NK) cells show that most of the
      cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an
      antibody, either naked or conjugated to radioactive isotopes or cytotoxic agents,
      may prove useful in the therapy of infant ALL as well as childhood and adult ALL
      patients whose blasts typically express FLT3.

PMID- 16651441
TI  - Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear
      factor-kappaB gene expression by soy isoflavones does not require estrogenic
      activity.
AB  - We have analyzed in molecular detail how soy isoflavones (genistein, daidzein,
      and biochanin A) suppress nuclear factor-kappaB (NF-kappaB)-driven interleukin-6
      (IL6) expression. In addition to its physiologic immune function as an acute
      stress cytokine, sustained elevated expression levels of IL6 promote chronic
      inflammatory disorders, aging frailty, and tumorigenesis. Our results in estrogen
      unresponsive fibroblasts, mitogen- and stress-activated protein kinase (MSK)
      knockout cells, and estrogen receptor (ER)-deficient breast tumor cells show that
      phytoestrogenic isoflavones can selectively block nuclear NF-kappaB
      transactivation of specific target genes (in particular IL6), independently of
      their estrogenic activity. This occurs via attenuation of mitogen-activated
      protein/extracellular signal-regulated kinase (ERK) kinase (MEK) and ERK
      activity, which further down-regulates MSK-dependent NF-kappaB p65 and histone H3
      phosphorylation. As constitutive NF-kappaB and MSK activity are hallmarks of
      aggressive metastatic ER-deficient breast cancer, the MSK signaling pathway may
      become an attractive target for chemotherapy.

PMID- 16651442
TI  - Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell
      death.
AB  - Doxorubicin (Adriamycin) is one of the most commonly used chemotherapeutic drugs
      and exhibits a wide spectrum of activity against solid tumors, lymphomas, and
      leukemias. Doxorubicin is classified as a topoisomerase II poison, although other
      mechanisms of action have been characterized. Here, we show that doxorubicin-DNA
      adducts (formed by the coadministration of doxorubicin with non-toxic doses of
      formaldehyde-releasing prodrugs) induce a more cytotoxic response in HL-60 cells
      than doxorubicin as a single agent. Doxorubicin-DNA adducts seem to be
      independent of classic topoisomerase II-mediated cellular responses (as observed
      by employing topoisomerase II catalytic inhibitors and HL-60/MX2 cells).
      Apoptosis induced by doxorubicin-DNA adducts initiates a caspase cascade that can
      be blocked by overexpressed Bcl-2, suggesting that adducts induce a classic mode
      of apoptosis. A reduction in the level of topoisomerase II-mediated double-strand
      breaks was also observed with increasing levels of doxorubicin-DNA adducts and
      increased levels of apoptosis, further confirming that adducts exhibit a separate
      mechanism of action compared with the classic topoisomerase II poison mode of
      cell death by doxorubicin alone. Collectively, these results indicate that the
      presence of formaldehyde transfers doxorubicin from topoisomerase II-mediated
      cellular damage to the formation of doxorubicin-DNA adducts, and that these
      adducts are more cytotoxic than topoisomerase II-mediated lesions. These results
      also show that doxorubicin can induce apoptosis by a non-topoisomerase II
      dependent mechanism, and this provides exciting new prospects for enhancing the
      clinical use of this agent and for the development of new derivatives and new
      tumor-targeted therapies.

PMID- 16651443
TI  - Disruption of the Y-box binding protein-1 results in suppression of the epidermal
      growth factor receptor and HER-2.
AB  - The overexpression of the epidermal growth factor receptor (EGFR) and HER-2
      underpin the growth of aggressive breast cancer; still, it is unclear what
      governs the regulation of these receptors. Our laboratories recently determined
      that the Y-box binding protein-1 (YB-1), an oncogenic transcription/translation
      factor, induced breast tumor cell growth in monolayer and in soft agar.
      Importantly, mutating YB-1 at Ser(102), which resides in the DNA-binding domain,
      prevented growth induction. We reasoned that the underlying cause for growth
      attenuation by YB-1(Ser(102)) is through the regulation of EGFR and/or HER-2. The
      initial link between YB-1 and these receptors was sought by screening primary
      tumor tissue microarrays. We determined that YB-1 (n = 389 cases) was positively
      associated with EGFR (P < 0.001, r = 0.213), HER-2 (P = 0.008, r = 0.157), and
      Ki67 (P < 0.0002, r = 0.219). It was inversely linked to the estrogen receptor (P
      < 0.001, r = -0.291). Overexpression of YB-1 in a breast cancer cell line
      increased HER-2 and EGFR. Alternatively, mutation of YB-1 at Ser(102) > Ala(102)
      prevented the induction of these receptors and rendered the cells less responsive
      to EGF. The mutant YB-1 protein was also unable to optimally bind to the EGFR and
      HER-2 promoters based on chromatin immunoprecipitation. Furthermore, knocking
      down YB-1 with small interfering RNA suppressed the expression of EGFR and HER-2.
      This was coupled with a decrease in tumor cell growth. In conclusion, YB
      1(Ser(102)) is a point of molecular vulnerability for maintaining the expression
      of EGFR and HER-2. Targeting YB-1 or more specifically YB-1(Ser(102)) are novel
      approaches to inhibiting the expression of these receptors to ultimately suppress
      tumor cell growth.

PMID- 16651444
TI  - 3,3'-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that
      can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human
      breast cancer cells.
AB  - Epidemiologic evidence suggests that high dietary intake of Brassica vegetables,
      such as broccoli, cabbage, and Brussels sprouts, protects against tumorigenesis
      in multiple organs. 3,3'-Diindolylmethane, one of the active products derived
      from Brassica vegetables, is a promising antitumor agent. Previous studies in our
      laboratory showed that 3,3'-diindolylmethane induced a G(1) cell cycle arrest in
      human breast cancer MCF-7 cells by a mechanism that included increased expression
      of p21. In the present study, the upstream events leading to p21 overexpression
      were further investigated. We show for the first time that 3,3'-diindolylmethane
      is a strong mitochondrial H(+)-ATPase inhibitor (IC(50) approximately 20
      micromol/L). 3,3'-Diindolylmethane treatment induced hyperpolarization of
      mitochondrial inner membrane, decreased cellular ATP level, and significantly
      stimulated mitochondrial reactive oxygen species (ROS) production. ROS
      production, in turn, led to the activation of stress-activated pathways involving
      p38 and c-Jun NH(2)-terminal kinase. Using specific kinase inhibitors (SB203580
      and SP600125), we showed the central role of p38 and c-Jun NH(2)-terminal kinase
      (JNK) pathways in 3,3'-diindolylmethane-induced p21 mRNA transcription. In
      addition, antioxidants significantly attenuated 3,3'-diindolylmethane-induced
      activation of p38 and JNK and induction of p21, indicating that oxidative stress
      is the major trigger of these events. To further support the role of ROS in 3,3'
      diindolylmethane-induced p21 overexpression, we showed that 3,3'-diindolylmethane
      failed to induce p21 overexpression in mitochondrial respiratory chain deficient
      rho(0) MCF-7 cells, in which 3,3'-diindolylmethane did not stimulate ROS
      production. Thus, we have established the critical role of enhanced mitochondrial
      ROS release in 3,3'-diindolylmethane-induced p21 up-regulation in human breast
      cancer cells.

PMID- 16651445
TI  - The role of mitogen-activated protein kinase phosphatase-1 in oxidative damage
      induced cell death.
AB  - Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a member of the
      MAPK phosphatase family that functions as a negative regulator of MAPK signaling.
      MKP-1 is induced by oxidative stress, but the role of its induction in cell death
      is not fully understood. Here, we show that hydrogen peroxide (H(2)O(2)) induces
      MKP-1 and activates MAPKs. Induction of MKP-1 by H(2)O(2) correlated with
      inactivation of p38 and c-Jun-NH(2)-kinase (JNK). Overexpression of MKP-1
      increased cell resistance to H(2)O(2)-induced death. Furthermore, we show by
      small interfering RNA silencing that down-regulation of MKP-1 increases
      phosphorylated p38 and JNK and subsequent cell death induced by H(2)O(2). More
      importantly, primary embryonic fibroblasts from mice lacking MKP-1 had a higher
      level of phosphorylated p38 and JNK and were more sensitive to H(2)O(2)-induced
      cell death compared with corresponding cells with MKP-1, indicating that p38 and
      JNK pathways may play important roles in H(2)O(2)-mediated cell death. Thus,
      these results suggest that activation of MKP-1 is a survival mechanism against
      oxidative damage.

PMID- 16651446
TI  - Combinational FLt3 ligand and granulocyte macrophage colony-stimulating factor
      treatment promotes enhanced tumor infiltration by dendritic cells and antitumor
      CD8(+) T-cell cross-priming but is ineffective as a therapy.
AB  - Dendritic cells play significant roles in the development and maintenance of
      antitumor immune responses. Therapeutic recruitment of dendritic cells into the
      tumor microenvironment has the potential to result in enhanced antitumor T-cell
      cross-priming against a broad array of naturally processed and presented tumor
      associated antigens. We have observed that the treatment of BALB/c mice bearing
      syngeneic CMS4 sarcomas with the combination of recombinant Flt3 ligand and
      recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for five
      sequential days is sufficient to optimize the number of tumor-infiltrating
      dendritic cells (TIDC). However, despite the significant increase in the number
      of TIDCs, the therapeutic benefit of Flt3 ligand and GM-CSF treatment is minimal.
      Therapy-associated TIDCs do not exhibit a "suppressed" or "suppressor" phenotype
      in vitro, and their enhanced numbers in cytokine-treated mice were associated
      with increased levels of peripheral antitumor CD8(+) T effector cells and with an
      augmented population of CD8(+) tumor-infiltrating lymphocytes (TIL). These data
      suggest that Flt3 ligand + GM-CSF therapy of murine tumors fails at a mechanistic
      point that is downstream of specific T-cell priming by therapy-induced TIDCs and
      the recruitment of these T cells into the tumor microenvironment. Based on the
      enhanced infiltration of tumors by CD4(+)CD25(+) TIL in Flt3 ligand + GM-CSF
      treated mice, this could reflect the dominant influence of regulatory T cells in
      situ.

PMID- 16651447
TI  - Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and
      tumor immunity.
AB  - Immunization of mice with plasmids encoding xenogeneic orthologues of tumor
      differentiation antigens can break immune ignorance and tolerance to self and
      induce protective tumor immunity. We sought to improve on this strategy by
      combining xenogeneic DNA vaccination with an agonist anti-glucocorticoid-induced
      tumor necrosis factor receptor family-related gene (GITR) monoclonal antibody
      (mAb), DTA-1, which has been shown previously both to costimulate activated
      effector CD4(+) and CD8(+) T cells and to inhibit the suppressive activity of
      CD4(+)CD25(+) regulatory T cells. We found that ligation of GITR with DTA-1 just
      before the second, but not the first, of 3 weekly DNA immunizations enhanced
      primary CD8(+) T-cell responses against the melanoma differentiation antigens
      gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased
      protection from a lethal challenge with B16 melanoma. This improved tumor
      immunity was associated with a modest increase in focal autoimmunity, manifested
      as autoimmune hypopigmentation. DTA-1 administration on this schedule also led to
      prolonged persistence of the antigen-specific CD8(+) T cells as well as to an
      enhanced recall CD8(+) T-cell response to a booster vaccination given 4 weeks
      after the primary immunization series. Giving the anti-GITR mAb both during
      primary immunization and at the time of booster vaccination increased the recall
      response even further. Finally, this effect on vaccine-induced CD8(+) T-cell
      responses was partially independent of CD4(+) T cells (both helper and
      regulatory), consistent with a direct costimulatory effect on the effector CD8(+)
      cells themselves.

PMID- 16651448
TI  - Ex vivo culture with interleukin (IL)-12 improves CD8(+) T-cell adoptive
      immunotherapy for murine leukemia independent of IL-18 or IFN-gamma but requires
      perforin.
AB  - In animal models and clinical trials, adoptive transfer of activated, antigen
      specific CD8(+) T cells mediates tumor regression in a cell dose-dependent
      manner. The cytokine interleukin (IL)-12 promotes CD8(+) T-cell cytotoxicity and,
      with IL-18, synergistically up-regulates IFN-gamma release. We have shown that
      culturing CD8(+) T cells ex vivo with IL-12 and IL-18 enhanced antitumor
      responses in vivo and in vitro using a model of C1498/ovalbumin, a murine acute
      myeloid leukemia cell line expressing the antigen ovalbumin. Activated ovalbumin
      specific CD8(+) T cells cultured with IL-12, IL-18, both, or neither were assayed
      for antigen-specific cytokine production and cytolytic activity and adoptively
      transferred to C57BL/6 mice with established tumors. Maximal IFN-gamma release
      occurred after T-cell culture with IL-12 and IL-18. Tumor-specific in vitro
      cytotoxicity was enhanced by IL-12, unaffected by addition of IL-18, and
      abrogated in perforin-deficient T cells irrespective of cytokine exposure. T
      cells cultured with IL-12 more effectively eliminated tumors, and addition of IL
      18 did not further augment responses. IFN-gamma-deficient CD8(+) T cells showed
      effective antitumor activity that was enhanced by IL-12 with or without IL-18.
      Perforin-deficient CD8(+) T cells were poor mediators of antitumor activity,
      though, and showed no improvement after culture with IL-12 and/or IL-18. Thus, ex
      vivo culture with IL-12 was sufficient to augment antigen-specific in vitro
      cytotoxicity and antitumor activity in vivo in an IFN-gamma-independent but
      perforin-dependent manner. Ex vivo culture with IL-12 may improve CD8(+) T-cell
      immunotherapy of cancer in the absence of donor cell-derived IFN-gamma via
      perforin-mediated cytolysis.

PMID- 16651449
TI  - Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen
      recognized by autologous CTL induced on human lung adenocarcinoma.
AB  - The purpose of our present study is to identify a tumor-specific antigen capable
      of inducing a specific cellular immune response in lung cancer patients. We
      established a lung adenocarcinoma cell line, designated as F1121L, and induced
      tumor-specific CTL clone H1 from regional lymph node lymphocytes of patient
      F1121. CTL clone H1 lysed autologous tumor cells in an HLA-B*1507-restricted
      manner, but not autologous EBV-B, phytohemagglutinin-blast cells, and K562. The
      CTL clone also recognized allogeneic HLA-B*1501- or 1507-positive lung cancer
      cell lines in the HLA-restricted manner. Using the CTL clone, we identified an
      antigen-coding gene by cDNA expression cloning technique. The gene consisted of
      556 bp, including an open reading frame consisted of 113 amino acids, designated
      as Kita-kyushu lung cancer antigen 1 (KK-LC-1). A 9-mer peptide (KK-LC-1(76-84);
      RQKRILVNL) was identified as an epitope peptide. The genomic DNA of this antigen
      was located in chromosome Xq22. A reverse transcription-PCR analysis revealed
      that the mRNA of this gene was only expressed in the testis among normal tissues.
      It was expressed in 9 of 18 (50%) allogeneic non-small-cell lung cancer cell
      lines and in 40 of 100 (40%) non-small-cell lung cancer tissues. We thus
      identified a new tumor antigen-coding gene categorized as a cancer/germline gene
      by an autologous lung cancer and CTL system. The new cancer/germline gene was
      located in Xq22, which is apparently different from the locations of previously
      reported cancer/germline genes.

PMID- 16651450
TI  - Menin links estrogen receptor activation to histone H3K4 trimethylation.
AB  - The product of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor
      gene, menin, is an integral component of MLL1/MLL2 histone methyltransferase
      complexes specific for Lys4 of histone H3 (H3K4). We show that menin is a
      transcriptional coactivator of the nuclear receptors for estrogen and vitamin D.
      Activation of the endogenous estrogen-responsive TFF1 (pS2) gene results in
      promoter recruitment of menin and in elevated trimethylation of H3K4. Knockdown
      of menin reduces both activated TFF1 (pS2) transcription and H3K4 trimethylation.
      In addition, menin can directly interact with the estrogen receptor-alpha
      (ERalpha) in a hormone-dependent manner. The majority of disease-related MEN1
      mutations prevent menin-ERalpha interaction. Importantly, ERalpha-interacting
      mutants are also defective in coactivator function. Our results indicate that
      menin is a critical link between recruitment of histone methyltransferase
      complexes and nuclear receptor-mediated transcription.

PMID- 16651451
TI  - Molecular evidence for independent origin of multifocal neuroendocrine tumors of
      the enteropancreatic axis.
AB  - Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have
      investigated whether multifocal intestinal carcinoid tumors and multifocal
      pancreatic endocrine tumors arise independently or whether they originate from a
      single clone with subsequent intramural or intrapancreatic spread. Twenty-four
      cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal
      pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from
      72 distinct tumor nodules using laser capture microdissection. Loss of
      heterozygosity (LOH) assays were done using markers for putative tumor suppressor
      genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21,
      18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on
      the tumors from eight female patients. Twenty-two of 24 (92%) cases showed
      allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of
      multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic
      endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for
      each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among
      some of the coexisting tumors, whereas other coexisting tumors displayed the same
      allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every
      individual tumor. X chromosome inactivation analysis showed a discordant pattern
      of nonrandom X chromosome inactivation in two of six informative cases and
      concordant pattern of nonrandom X chromosome inactivation in the four remaining
      informative cases. Our data suggest that some multifocal neuroendocrine tumors of
      the enteropancreatic axis arise independently, whereas others originate as a
      single clone with subsequent local and discontinuous metastasis.

PMID- 16651452
TI  - Immunization of stage IV melanoma patients with Melan-A/MART-1 and gp100 peptides
      plus IFN-alpha results in the activation of specific CD8(+) T cells and
      monocyte/dendritic cell precursors.
AB  - The use of IFN-alpha in clinical oncology has generally been based on the
      rationale of exploiting its antiproliferative and antiangiogenic activities.
      However, IFN-alpha also exhibits enhancing effects on T-cell and dendritic cell
      functions, which may suggest a novel use as a vaccine adjuvant. We have carried
      out a pilot phase I-II trial to determine the effects of IFN-alpha, administered
      as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on
      immune responses in stage IV melanoma patients. In five of the seven evaluable
      patients, a consistent enhancement of CD8(+) T cells recognizing modified and
      native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was
      observed. Moreover, vaccination induced an increase in CD8(+) T-cell binding to
      HLA tetramers containing the relevant peptides and an increased frequency of
      CD45RA(+)CCR7(-) (terminally differentiated effectors) and CD45RA(-)CCR7(-)
      (effector memory) cells. In all patients, treatment augmented significantly the
      percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell
      fraction. An increased expression of CD40 and CD86 costimulatory molecules in
      monocytes was also observed. Notably, postvaccination monocytes from two of the
      three patients showing stable disease or long disease-free survival showed an
      enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10
      when tested in mixed leukocyte reaction assays, associated to a boost of antigen
      and melanoma-specific CD8(+) T cells. Although further clinical studies are
      needed to show the adjuvant activity of IFN-alpha, the present data represent an
      important starting point for considering a new clinical use of IFN-alpha and new
      immunologic end points, potentially predictive of clinical response.

PMID- 16651453
TI  - Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane
      induced cell growth inhibition and apoptosis in breast cancer cells.
AB  - The phytochemical indole-3-carbinol (I3C), found in cruciferous vegetables, and
      its major acid-catalyzed reaction product 3,3'-diindolylmethane (DIM) showed
      anticancer activity mediated by its pleiotropic effects on cell cycle
      progression, apoptosis, carcinogen bioactivation, and DNA repair. To further
      elucidate the molecular mechanism(s) by which 3,3'-diindolylmethane exerts its
      effects on breast cancer cells, we have used microarray gene expression profiling
      analysis. We found a total of 1,238 genes altered in 3,3'-diindolylmethane
      treated cells, among which 550 genes were down-regulated and 688 genes were up
      regulated. Clustering analysis showed significant alterations in some genes that
      are critically involved in the regulation of cell growth, cell cycle, apoptosis,
      and signal transduction, including down-regulation of survivin. Previous studies
      have shown that antiapoptotic protein survivin is overexpressed in many human
      cancers, including breast cancer. However, very little or no information is
      available regarding the consequence of down-regulation of survivin for cancer
      therapy. We, therefore, hypothesized that down-regulation of survivin as observed
      by 3,3'-diindolylmethane could be an important approach for the treatment of
      breast cancer. We have tested our hypothesis using multiple molecular approaches
      and found that 3,3'-diindolylmethane inhibited cell growth and induced apoptosis
      in MDA-MB-231 breast cancer cells by down-regulating survivin, Bcl-2, and cdc25A
      expression and also caused up-regulation of p21(WAF1) expression, which could be
      responsible for cell cycle arrest. Down-regulation of survivin by small
      interfering RNA before 3,3'-diindolylmethane treatment resulted in enhanced cell
      growth inhibition and apoptosis, whereas overexpression of survivin by cDNA
      transfection abrogated 3,3'-diindolylmethane-induced cell growth inhibition and
      apoptosis. These results suggest that targeting survivin by 3,3'-diindolylmethane
      could be a new and novel approach for the prevention and/or treatment of breast
      cancer.

PMID- 16651454
TI  - Dose-response relationship between cooking fumes exposures and lung cancer among
      Chinese nonsmoking women.
AB  - The high incidence of lung cancer among Chinese females, despite a low smoking
      prevalence, remains poorly explained. Cooking fume exposure during frying could
      be an important risk factor. We carried out a population-based case-control study
      in Hong Kong. Cases were Chinese female nonsmokers with newly diagnosed primary
      lung cancer. Controls were female nonsmokers randomly sampled from the community,
      frequency matched by age groups. Face-to-face interviews were conducted using a
      standardized questionnaire. The "total cooking dish-years," categorized by
      increments of 50, was used as a surrogate of cooking fumes exposure. Multiple
      unconditional logistic regression was used to estimate the odds ratios (OR) for
      different levels of exposure after adjusting for various potential confounding
      factors. We interviewed 200 cases and 285 controls. The ORs of lung cancer across
      increasing levels of cooking dish-years were 1, 1.17, 1.92, 2.26, and 6.15. After
      adjusting for age and other potential confounding factors, the increasing trend
      of ORs with increasing exposure categories became clearer, being 1, 1.31, 4.12,
      4.68, and 34. The OR of lung cancer was highest for deep-frying (2.56 per 10 dish
      years) followed by that of frying (1.47), and stir-frying had the lowest OR
      (1.12) among the three methods. Cumulative exposure to cooking by means of any
      form of frying could increase the risk of lung cancer in Hong Kong nonsmoking
      women. Practical means to reduce exposures to cooking fumes should be given top
      priority in future research.

PMID- 16651455
TI  - DNA sequence context affects repair of the tobacco-specific adduct O(6)-[4-Oxo-4
      (3-pyridyl)butyl]guanine by human O(6)-alkylguanine-DNA alkyltransferases.
AB  - The repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) protects cells
      from the mutagenic and carcinogenic effects of alkylating agents by removing O(6)
      alkylguanine adducts from DNA. Recently, we established that AGT protects against
      the mutagenic effects of pyridyloxobutylation resulting from the metabolic
      activation of the tobacco-specific nitrosamines (TSNA) 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone and N-nitrosonornicotine by repairing O(6)-[4-oxo-4-(3
      pyridyl)butyl]guanine (O(6)-pobG). There have been several epidemiologic studies
      examining the association between the I143V/K178R AGT genotype and lung cancer
      risk. Two studies have found positive associations, suggesting that AGT proteins
      differ in their repair of DNA damage caused by TSNA. However, it is not known how
      this genotype alters the biochemical activity of AGT. We proposed that AGT
      proteins may differ in their ability to remove large O(6)-alkylguanine adducts,
      such as O(6)-pobG, from DNA. Therefore, we examined the repair of O(6)-pobG by
      wild-type (WT) human, I143V/K178R, and L84F AGT proteins when contained in
      multiple sequence contexts, including the twelfth codon of H-ras, a mutational
      hotspot within this oncogene. The AGT-mediated repair of O(6)-pobG was more
      profoundly influenced by sequence context than that of O(6)-methylguanine. These
      differences are not the result of secondary structure (hairpin) formation in DNA.
      In addition, the I143V/K178R variant seems less sensitive to the effects of
      sequence context than the WT or L84F proteins. These studies indicate that the
      sequence dependence of O(6)-pobG repair by human AGT (hAGT) varies with subtle
      changes in protein structure. These data establish a novel functional difference
      between the I143V/K178R protein and other hAGTs in the repair of a
      toxicologically relevant substrate, O(6)-pobG.

PMID- 16651456
TI  - Nonsteroidal anti-inflammatory drugs and the esophageal inflammation-metaplasia
      adenocarcinoma sequence.
AB  - Observational studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs)
      reduce the risk of esophageal adenocarcinoma, but it is not known at what stage
      they may act in the esophageal inflammation-metaplasia-adenocarcinoma sequence.
      In an all-Ireland case-control study, we investigated the relationship between
      the use of NSAIDs and risk of reflux esophagitis, Barrett's esophagus, and
      esophageal adenocarcinoma. Patients with esophageal adenocarcinoma, long-segment
      Barrett's esophagus and population controls were recruited from throughout
      Ireland. Esophagitis patients were recruited from Northern Ireland only. Data
      were collected on known and potential risk factors for esophageal adenocarcinoma
      and on the use of NSAIDs, including aspirin, at least 1 year before interview.
      Associations between use of NSAIDs and the stages of the esophageal inflammation
      metaplasia-adenocarcinoma sequence were estimated by multiple logistic
      regression. In total, 230 reflux esophagitis, 224 Barrett's esophagus, and 227
      esophageal adenocarcinoma and 260 population controls were recruited. Use of
      aspirin and NSAIDs was associated with a reduced risk of Barrett's esophagus
      [odds ratio [OR; 95% confidence interval (95% CI)], 0.53 (0.31-0.90) and 0.40
      (0.19-0.81), respectively] and esophageal adenocarcinoma [OR (95% CI), 0.57 (0.36
      0.93) and 0.58 (0.31-1.08), respectively]. Barrett's esophagus and esophageal
      adenocarcinoma patients were less likely than controls to have used NSAIDs.
      Selection or recall bias may explain these results and the results of previous
      observational studies indicating a protective effect of NSAIDs against esophageal
      adenocarcinoma. If NSAIDs have a true protective effect on the esophageal
      inflammation-metaplasia-adenocarcinoma sequence, they may act early in the
      sequence.

PMID- 16651457
TI  - Prognostic implications of left ventricular mass among Hispanics: the Northern
      Manhattan Study.
AB  - Hispanics may carry a similar burden of increased left ventricular mass (LVM) as
      non-Hispanic blacks but whether LVM portends a worse outcome among Hispanics is
      largely unknown. We prospectively evaluated 1081 Hispanics enrolled in the
      Northern Manhattan Study during the period of 1993 to 2001. Subjects were aged >
      or =40 years and free of prior myocardial infarction or stroke. LVM was defined
      echocardiographically and indexed for height(2.7). Cox proportional hazards
      models were used to assess the risk of vascular events with adjustments for age,
      gender, systolic blood pressure, diabetes, and smoking. LVM averaged 48.4+/-15
      gm/ht(2.7) and on multivariate analysis was significantly associated with the
      combined end point of myocardial infarction, stroke, or vascular death (adjusted
      hazard ratio 1.34 per SD change in LVM [95% CI 1.10 to 1.63]). During a mean of
      57 months of follow-up, 74 vascular events occurred. The annual rate of vascular
      events was 21.8 per 1000 patient-years in the highest quartile of LVM and 8.6 per
      1000 patient-years in the lowest quartile (P=0.007). These data demonstrate in a
      large population-based sample that increased LVM yields independent prognostic
      information among Hispanics, predicting a higher incidence of events attributable
      to vascular disease in this understudied population. Our findings identify the
      Hispanic population with increased LVM as a high-risk subgroup.

PMID- 16651458
TI  - Gender differences of cardiovascular disease: new perspectives for estrogen
      receptor signaling.

PMID- 16651459
TI  - Validation of a generalized transfer function to noninvasively derive central
      blood pressure during exercise.
AB  - Exercise brachial blood pressure (BP) predicts mortality, but because of wave
      reflection, central (ascending aortic) pressure differs from brachial pressure.
      Exercise central BP may be clinically important, and a noninvasive means to
      derive it would be useful. The purpose of this study was to test the validity of
      a noninvasive technique to derive exercise central BP. Ascending aortic pressure
      waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30
      patients (56+/-9 years; 21 men) undergoing diagnostic coronary angiography.
      Simultaneous recordings of the derived central pressure waveform were acquired
      using servocontrolled radial tonometry at rest and during supine cycling. Pulse
      wave analysis of the direct and derived pressure signals was performed offline
      (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate
      were increased by 20+/-10 mm Hg and 15+/-7 bpm, respectively, and central
      systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high
      correlation between invasive and noninvasive techniques with a mean difference
      (+/-SD) for central systolic BP of -1.3+/-3.2 mm Hg at rest and -4.7+/-3.3 mm Hg
      at peak exercise (for both r=0.995; P<0.001). Conversely, systolic BP was
      significantly higher peripherally than centrally at rest (155+/-33 versus 138+/
      32 mm Hg; mean difference, -16.3+/-9.4 mm Hg) and during exercise (180+/-34
      versus 164+/-33 mm Hg; mean difference, -15.5+/-10.4 mm Hg; for both P<0.001).
      True myocardial afterload is not reliably estimated by peripheral systolic BP.
      Radial tonometry and pulse wave analysis is an accurate technique for the
      noninvasive determination of central BP at rest and during exercise.

PMID- 16651460
TI  - Angiotensin type-1 receptor A1166C gene polymorphism correlates with oxidative
      stress levels in human heart failure.
AB  - Oxidative stress plays a critical role in the pathogenesis of cardiovascular
      disease and diabetes. Studies in vascular cells and experimental animals have
      demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation
      of reactive oxygen species by activating nicotinamide-adenine dinucleotide
      phosphate oxidases, but the relevance of this pathway to human heart disease has
      not been established. Here we demonstrate that a polymorphism in the AT1R gene
      (A1166C), linked to increased receptor activity, is associated with elevated
      levels of oxidative stress markers in heart failure patients but not in healthy
      controls. Plasma protein carbonyls (PCs), a marker of oxidative protein
      modification, were 10-fold higher in heart-failure patients compared with
      controls [geometric means and 95% CIs for patients, 75 (57 to 100) pmol/mg;
      controls, 5 (4 to 7) pmol/mg; P<0.001]. Moreover, levels of PCs were 50-fold
      higher in patients homozygous for the polymorphism (CC) than in controls and
      significantly higher than the AA and AC genotype patient groups [CC: 273 (135
      550); AC: 59 (35-98); AA: 65 (40-106) pmol/mg; P<0.001]. Levels of
      myeloperoxidase were also modestly increased in heart-failure patients [51 (46
      57) ng/mL] compared with controls [37 (32-44) ng/mL; P<0.001], but were
      especially elevated in patients with a CC genotype [CC: 72 (58-89); AC: 52 (44
      61); AA: 39 (34-46) ng/mL; P<0.001]. The AT1R genotype was demonstrated to be an
      independent predictor of both PCs and myeloperoxidase levels in heart-failure
      patients. These findings suggest that oxidative stress in human heart failure is
      regulated via angiotensin signaling and may involve the nicotinamide dinucleotide
      oxidase pathway.

PMID- 16651461
TI  - Hypoxia-induced endothelial NO synthase gene transcriptional activation is
      mediated through the tax-responsive element in endothelial cells.
AB  - Although hypoxia is known to induce upregulation of endothelial NO synthase
      (eNOS) gene expression, the underlying mechanism is largely unclear. In this
      study, we show that hypoxia increases eNOS gene expression through the binding of
      phosphorylated cAMP-responsive element binding (CREB) protein (pCREB) to the eNOS
      gene promoter. Hypoxia (1% O2) increased both eNOS expression and NO production,
      peaking at 24 hours, in bovine aortic endothelial cells, and these increases were
      accompanied by increases in pCREB. Treatment with the protein kinase A inhibitor
      H-89 or transfection with dominant-negative inhibitor of CREB reversed the
      hypoxia-induced increases in eNOS expression and NO production, with concomitant
      inhibition of the phosphorylation of CREB induced by hypoxia, suggesting an
      involvement of protein kinase A/pCREB-mediated pathway. To map the regulatory
      elements of the eNOS gene responsible for pCREB binding under hypoxia, we
      constructed an eNOS gene promoter (-1600 to +22 nucleotides) fused with a
      luciferase reporter gene [pGL2-eNOS(-1600)]. Hypoxia (for 24-hour incubation)
      increased the promoter activity by 2.36+/-0.18-fold in the bovine aortic
      endothelial cells transfected with pGL2-eNOS(-1600). However, progressive 5'
      deletion from -1600 to -873 completely attenuated the hypoxia-induced increase in
      promoter activity. Electrophoretic mobility shift, anti-pCREB antibody
      supershift, and site-specific mutation analyses showed that pCREB is bound to the
      Tax-responsive element (TRE) site, a cAMP-responsive element-like site, located
      at -924 to -921 of the eNOS promoter. Our data demonstrate that the interaction
      between pCREB and the Tax-responsive element site within the eNOS promoter may
      represent a novel mechanism for the mediation of hypoxia-stimulated eNOS gene
      expression.

PMID- 16651462
TI  - Human bird flu infection: is there any relationship to hypertension?

PMID- 16651463
TI  - Acute cardiovascular and sympathetic effects of nicotine replacement therapy.
AB  - Sympathetic overactivity is implicated in the increased cardiovascular risk of
      cigarette smokers. Excitatory nicotinic receptors are present on peripheral
      chemoreceptor cells. Chemoreceptors located in the carotid and aortic bodies
      increase ventilation (Ve), blood pressure (BP), heart rate (HR), and sympathetic
      nerve activity to muscle circulation (MSNA) in response to hypoxia. We tested the
      hypothesis that nicotine replacement therapy (NRT) increases MSNA and
      chemoreceptor sensitivity to hypoxia. Sixteen young healthy smokers were included
      in the study (8 women). After a randomized and blinded sublingual administration
      of a 4-mg tablet of nicotine or placebo, we measured minute Ve, HR, mean BP, and
      MSNA during normoxia and 5 minutes of isocapnic hypoxia. Maximal voluntary end
      expiratory apneas were performed at baseline and at the end of the fifth minute
      of hypoxia. Nicotine increased HR by 7+/-3 bpm, mean BP by 5+/-2 mm Hg, and MSNA
      by 4+/-1 bursts/min, whereas subjects breathed room air (all P<0.05). During
      hypoxia, nicotine also raised HR by 8+/-2 bpm, mean BP by 2+/-1 mm Hg, and MSNA
      by 7+/-2 bursts/min (all P<0.05). Nicotine increased MSNA during the apneas
      performed in normoxia and hypoxia (P<0.05). Nicotine also raised the product of
      systolic BP and HR, a marker of cardiac oxygen consumption, during normoxia,
      hypoxia, and the apneas (P<0.05). Ve, apnea duration, and O2 saturation during
      hypoxia and the apneas remained unaffected. In conclusion, sympathoexcitatory
      effects of NRT are not because of an increased chemoreflex sensitivity to
      hypoxia. NRT increases myocardial oxygen consumption in periods of reduced oxygen
      availability.

PMID- 16651464
TI  - Recommendations for evaluating compliance and persistence with hypertension
      therapy using retrospective data.

PMID- 16651465
TI  - Adiponectin replenishment ameliorates obesity-related hypertension.
AB  - Patients with obesity are susceptible to hypertension. We have reported that the
      plasma adiponectin levels are decreased in obesity and that adiponectin has many
      defensive properties against obesity-related diseases, such as type 2 diabetes
      and coronary artery disease. The aim of this study was to determine the
      relationship between adiponectin and hypertension in mice. We measured blood
      pressure and heart rate directly by a catheter in the carotid artery and
      indirectly by automatic sphygmomanometer at the tail artery. Obese KKAy mice had
      significantly lower plasma adiponectin levels and higher systolic blood pressure
      than control C57BL/6J mice at 21 weeks of age. Adenovirus-delivered adiponectin
      significantly decreased blood pressure in KKAy mice. The direct role of
      adiponectin on blood pressure regulation under insulin resistance-free state was
      investigated in adiponectin-knockout (KO) mice. Adiponectin KO mice developed
      hypertension when maintained on a high-salt diet (8% NaCl) without insulin
      resistance. The hypertension of salt-fed adiponectin KO mice was associated with
      reduced mRNA levels of endothelial NO synthase (eNOS) and prostaglandin I(2)
      synthase in aorta and low metabolite levels of endothelial NO synthase and
      prostaglandin I(2) synthase in plasma. Adiponectin therapy lowered the elevated
      blood pressure and corrected the above mRNA levels to those of the wild type. Our
      results suggest that hypoadiponectinemia contributes to the development of
      obesity-related hypertension, at least in part, directly, in addition to its
      effect via insulin resistance, and that adiponectin therapy can be potentially
      useful for hypertension in patients with the metabolic syndrome.

PMID- 16651466
TI  - Novel locus for an inherited cardiomyopathy maps to chromosome 7.
AB  - BACKGROUND: Genetic mutations are the most common cause of hypertrophic
      cardiomyopathy (HCM) and an increasingly recognized cause of dilated
      cardiomyopathy. Autosomal dominant HCM is caused by mutations in sarcomere
      proteins; such mutations are not universally present, however, and fail to
      account for &40% of cases of phenotypic HCM. To add further complexity, other
      genetic origins can mimic the gross clinical phenotype of HCM, and mutations in
      sarcomere genes have been demonstrated to cause dilated cardiomyopathy. METHODS
      AND RESULTS: To explore novel genetic causes of inherited cardiomyopathies,
      genome-wide linkage analysis was used to study one kindred (4 generations, 32
      individuals) with predominant clinical features of left ventricular hypertrophy
      in addition to cardiac dilation, end-stage heart failure, and sudden death. Of
      note, histopathology from 2 family members did not demonstrate myocyte disarray
      and fibrosis, indicating that this phenotype is not typical sarcomere mutation
      HCM. Direct DNA sequencing was performed on sarcomere genes known to cause HCM
      and dilated cardiomyopathy, and no mutations were identified. Linkage was then
      established to a novel locus on chromosome 7 (7p12.1-7q21). A maximum 2-point
      logarithm of odds score of 4.11 was obtained. Recombination events refine the
      disease interval between D7S506 and D7S3314, corresponding to a distance of 27.2
      megabases. CONCLUSIONS: The discovery of a novel genetic locus in this family
      provides more evidence that molecular pathways leading to inherited cardiac
      hypertrophy extend beyond the sarcomere. Identification of the causal gene
      mutation and additional genotype-phenotype correlation studies will provide
      fundamental insight into mechanisms of cardiac remodeling.

PMID- 16651467
TI  - Polymorphism in the beta2-adrenergic receptor and lipoprotein lipase genes as
      risk determinants for idiopathic venous thromboembolism: a multilocus, population
      based, prospective genetic analysis.
AB  - BACKGROUND: Candidate genes in inflammation, thrombosis, coagulation, and lipid
      metabolism pathways have been implicated in venous thromboembolism (VTE). METHODS
      AND RESULTS: Using DNA samples collected at baseline in the Physicians' Health
      Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304
      individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases)
      and among 2070 individuals who remained free of reported vascular disease over a
      mean follow-up of 13.2 years to prospectively determine whether these gene
      polymorphisms contribute to the risk of VTE. For idiopathic VTE, in addition to
      the factor V (Leiden) mutation (odds ratio [OR], 5.13; 95% confidence interval
      [CI], 3.24 to 8.14; P<0.0001; false discovery rate [FDR], P<0.0001), an N291S
      lipoprotein lipase gene polymorphism (OR, 3.09; 95% CI, 1.56 to 6.09; P=0.001;
      FDR, P=0.036) and a Q27E beta2-adrenergic receptor gene polymorphism (OR, 1.40;
      95% CI, 1.09 to 1.79; P=0.006; FDR, P=0.036) were found to be significantly
      associated with increased risk. For secondary VTE, a Q360H apolipoprotein A4 gene
      polymorphism (OR, 0.34; 95% CI, 0.18 to 0.65; P=0.001; FDR, P=0.07) and an I50V
      interleukin-4 receptor polymorphism (OR, 0.66; 95% CI, 0.52 to 0.84; P=0.0009;
      FDR, P=0.07) were moderately, but not statistically and significantly, associated
      with reduced risk after adjustment for multiple comparisons. CONCLUSIONS: These
      present findings are hypothesis generating and require replication and
      confirmation in an independent investigation.

PMID- 16651468
TI  - Characteristics and baseline clinical predictors of future fatal versus nonfatal
      coronary heart disease events in older adults: the Cardiovascular Health Study.
AB  - BACKGROUND: Although >80% of annual coronary heart disease (CHD) deaths occur in
      adults aged >65 years and the population is aging rapidly, CHD event fatality and
      its predictors in the elderly have not been well described. METHODS AND RESULTS:
      The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or
      =65 years occurring during enrollment in the Cardiovascular Health Study during
      1989-2001 was identified and adjudicated. Characteristics measured at
      examinations before the event were examined for associations with case fatality
      (death before hospitalization or hospital discharge) and for differences in
      predictors by demographics or clinical history. During a median follow-up of 8.2
      years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased
      slightly over time, ranging from 28% to 30% per year in the early 1990s versus
      23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower
      odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence
      interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but
      higher with age and prior CHD (MI, angina, or revascularization). When considered
      alone, many subclinical disease measures, such as common carotid intima-media
      thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG
      abnormality, and traditional risk factors, such as diabetes and hypertension,
      were associated with fatality. In multivariable analysis, independent predictors
      of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41),
      prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43),
      diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI,
      1.07 to 1.37), adjusted for gender and each other. Prior congestive heart
      failure, regardless of left ventricular systolic function, age, gender, or prior
      CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups.
      CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains
      substantial, with easily identifiable risk factors that may be different from
      those that predict incident disease. In the elderly in whom the risk/benefit of
      therapies may be influenced by multiple competing comorbidities and care needs,
      risk stratification possibly may be improved further by focusing more aggressive
      care on specific patients, especially those with a history of congestive heart
      failure or prior CHD.

PMID- 16651469
TI  - Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes.
AB  - BACKGROUND: Cyclic guanosine monophosphate (cGMP) is the common second messenger
      for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides,
      such as atrial or brain natriuretic peptide, which activate the soluble and
      particulate forms of guanylyl cyclase, respectively. However, natriuretic
      peptides and NO donors exert different effects on cardiac and vascular smooth
      muscle function. We therefore tested whether these differences are due to an
      intracellular compartmentation of cGMP and evaluated the role of
      phosphodiesterase (PDE) subtypes in this process. METHODS AND RESULTS:
      Subsarcolemmal cGMP signals were monitored in adult rat cardiomyocytes by
      expression of the rat olfactory cyclic nucleotide-gated (CNG) channel alpha
      subunit and recording of the associated cGMP-gated current (ICNG). Atrial
      natriuretic peptide (10 nmol/L) or brain natriuretic peptide (10 nmol/L) induced
      a clear activation of ICNG, whereas NO donors (S-nitroso-N-acetyl-penicillamine,
      diethylamine NONOate, 3-morpholinosydnonimine, and spermine NO, all at 100
      micromol/L) had little effect. The ICNG current was strongly potentiated by
      nonselective PDE inhibition with isobutyl methylxanthine (100 micromol/L) and by
      the PDE2 inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (10 micromol/L) and Bay
      60-7550 (50 nmol/L). Surprisingly, sildenafil, a PDE5 inhibitor, produced a dose
      dependent increase of I(CNG) activated by NO donors but had no effect (at 100
      nmol/L) on the current elicited by atrial natriuretic peptide. CONCLUSIONS: These
      results indicate that in rat cardiomyocytes (1) the particulate cGMP pool is
      readily accessible at the plasma membrane, whereas the soluble pool is not; and
      (2) PDE5 controls the soluble but not the particulate pool, whereas the latter is
      under the exclusive control of PDE2. Differential spatiotemporal distributions of
      cGMP may therefore contribute to the specific effects of natriuretic peptides and
      NO donors on cardiac function.

PMID- 16651470
TI  - Outcome of watchful waiting in asymptomatic severe mitral regurgitation.
AB  - BACKGROUND: The management of asymptomatic severe mitral regurgitation remains
      controversial. The aim of this study was to evaluate the outcome of a watchful
      waiting strategy in which patients are referred to surgery when symptoms occur or
      when asymptomatic patients develop left ventricular (LV) enlargement, LV
      dysfunction, pulmonary hypertension, or recurrent atrial fibrillation. METHODS
      AND RESULTS: A total of 132 consecutive asymptomatic patients (age 55+/-15 years,
      49 female) with severe degenerative mitral regurgitation (flail leaflet or valve
      prolapse) were prospectively followed up for 62+/-26 months. Patients underwent
      serial clinical and echocardiographic examinations and were referred for surgery
      when the criteria mentioned above were fulfilled. Overall survival was not
      statistically different from expected survival either in the total group or in
      the subgroup of patients with flail leaflet. Eight deaths were observed. Thirty
      eight patients developed criteria for surgery (symptoms, 24; LV criteria, 9;
      pulmonary hypertension or atrial fibrillation, 5). Survival free of any
      indication for surgery was 92+/-2% at 2 years, 78+/-4% at 4 years, 65+/-5% at 6
      years, and 55+/-6% at 8 years. Patients with flail leaflet tended to develop
      criteria for surgery slightly but not significantly earlier. There was no
      operative mortality. Postoperative outcome was good with regard to survival,
      symptomatic status, and postoperative LV function. CONCLUSIONS: Asymptomatic
      patients with severe degenerative mitral regurgitation can be safely followed up
      until either symptoms occur or currently recommended cutoff values for LV size,
      LV function, or pulmonary hypertension are reached. This management strategy is
      associated with good perioperative and postoperative outcome but requires careful
      follow-up.

PMID- 16651471
TI  - Histological assessment of 526 symptomatic carotid plaques in relation to the
      nature and timing of ischemic symptoms: the Oxford plaque study.
AB  - BACKGROUND: Atherosclerotic plaque at the carotid bifurcation is often associated
      with transient ischemic attack (TIA) and ischemic stroke, but the mechanisms are
      not completely understood. Previous histological studies have been too small or
      insufficiently detailed to reliably determine the temporal course of features of
      plaque instability or to stratify analyses by the nature of presenting symptoms.
      METHODS AND RESULTS: We performed the largest-ever histological study of
      symptomatic carotid plaques from consecutive patients (n=526) undergoing
      endarterectomy and related detailed reproducible histological assessments to the
      nature and timing of presenting symptoms. There was a high prevalence of many
      features of coronary-type plaque instability. Dense plaque inflammation
      (especially infiltration with macrophages) was the feature most strongly
      associated with both cap rupture (odds ratio 3.39, 95% confidence interval 2.31
      to 4.98, P<0.001) and time since stroke (P=0.001). Strong negative associations
      with time since stroke were also seen for cap rupture (P=0.02), overall plaque
      inflammation (P=0.003), and "unstable plaque" (P=0.001). Although plaques removed
      < or =60 days after the most recent event were more unstable after a stroke than
      after a TIA, the instability persisted after a TIA, and plaques removed >180 days
      after most recent event were less unstable after a stroke than after a TIA
      (plaque inflammation: < or =60 days, odds ratio 2.33 [95% confidence interval
      0.76 to 7.19]; >180 days, 0.36 [0.16 to 0.84]; P=0.008; unstable plaque: odds
      ratio 3.27 [95% confidence interval 0.93 to 11.50] versus 0.74 [0.33 to 1.69],
      P=0.05). CONCLUSIONS: Pathology of recently symptomatic carotid plaques is
      similar to that of culprit coronary plaques, with strong correlations between
      macrophage infiltration and plaque instability. The tendency for plaque
      inflammation and overall instability to persist with time after a TIA but to
      decrease with time after a stroke suggests that the nature of the underlying
      pathology may differ.

PMID- 16651472
TI  - Creation of engineered cardiac tissue in vitro from mouse embryonic stem cells.
AB  - BACKGROUND: Embryonic stem (ES) cells can terminally differentiate into all types
      of somatic cells and are considered a promising source of seed cells for tissue
      engineering. However, despite recent progress in in vitro differentiation and in
      vivo transplantation methodologies of ES cells, to date, no one has succeeded in
      using ES cells in tissue engineering for generation of somatic tissues in vitro
      for potential transplantation therapy. METHODS AND RESULTS: ES-D3 cells were
      cultured in a slow-turning lateral vessel for mass production of embryoid bodies.
      The embryoid bodies were then induced to differentiate into cardiomyocytes in a
      medium supplemented with 1% ascorbic acid. The ES cell-derived cardiomyocytes
      were then enriched by Percoll gradient centrifugation. The enriched
      cardiomyocytes were mixed with liquid type I collagen supplemented with Matrigel
      to construct engineered cardiac tissue (ECT). After in vitro stretching for 7
      days, the ECT can beat synchronously and respond to physical and pharmaceutical
      stimulation. Histological, immunohistochemical, and transmission electron
      microscopic studies further indicate that the ECTs both structurally and
      functionally resemble neonatal native cardiac muscle. Markers related to
      undifferentiated ES cell contamination were not found in reverse transcriptase
      polymerase chain reaction analysis of the Percoll-enriched cardiomyocytes. No
      teratoma formation was observed in the ECTs implanted subcutaneously in nude mice
      for 4 weeks. CONCLUSIONS: ES cells can be used as a source of seed cells for
      cardiac tissue engineering. Additional work remains to demonstrate engraftment of
      the engineered heart tissue in the case of cardiac defects and its functional
      integrity within the host's remaining healthy cardiac tissue.

PMID- 16651473
TI  - Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by
      doxorubicin.
AB  - BACKGROUND: Doxorubicin (DOX) is an important antineoplastic agent. However, the
      associated cardiotoxicity, possibly mediated by the production of reactive oxygen
      species, has remained a significant and dose-limiting clinical problem. Our
      hypothesis is that the hematopoietic/megakaryocytopoietic growth factor
      thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might
      involve antiapoptotic mechanism exerted on cardiomyocytes. METHODS AND RESULTS:
      In vitro investigations on H9C2 cell line and spontaneously beating cells of
      primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of
      DOX-induced acute cardiomyopathy, were performed. Our results showed that
      pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells
      and beating rates of neonatal myocytes, with effects similar to those of
      dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX
      induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active
      caspase-3, and mitochondrial membrane potential. In the mouse model,
      administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly
      reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count,
      cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and
      animal mortality. Using Doppler echocardiography, we observed increased heart
      rate, fractional shortening, and cardiac output in animals pretreated with TPO
      compared with those receiving DOX alone. CONCLUSIONS: These data have provided
      the first evidence that TPO is a protective agent against DOX-induced cardiac
      injury. We propose to further explore an integrated program, incorporating TPO
      with other protocols, for treatment of DOX-induced cardiotoxicity and other forms
      of cardiomyopathy.

PMID- 16651474
TI  - Role of diuretics in the prevention of heart failure: the Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial.
AB  - BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent
      in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent
      Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of
      chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS:
      ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk
      hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were
      examined with proportional-hazards models. Relative risks (95% confidence
      intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35
      (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards
      assumption of constant relative risk over time was not valid. A more appropriate
      model showed relative risks of amlodipine or lisinopril versus chlorthalidone
      during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001),
      and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58).
      There was no significant interaction between prior medication use and treatment.
      Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were
      137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and
      lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin
      converting enzyme inhibitors, and calcium channel blockers in the treatment
      groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus
      amlodipine or lisinopril use during year 1. Subsequently, risk for those
      individuals taking chlorthalidone versus amlodipine remained decreased but less
      so, whereas it was equivalent to those given lisinopril. Prior medication use,
      follow-up blood pressures, and concomitant medications are unlikely to explain
      most of the HF differences. Diuretics are superior to calcium channel blockers
      and, at least in the short term, angiotensin-converting enzyme inhibitors in
      preventing HF in hypertensive individuals.

PMID- 16651475
TI  - Inflammation in atherosclerosis: some thoughts about acute coronary syndromes.

PMID- 16651476
TI  - Images in cardiovascular medicine. Stereolithographic biomodeling of congenital
      heart disease by multislice computed tomography imaging.

PMID- 16651477
TI  - Images in cardiovascular medicine. Implantation of a drug-eluting stent for the
      coronary artery stenosis of Takayasu arteritis: de novo and in-stent restenosis.

PMID- 16651478
TI  - Images in cardiovascular medicine. Pheochromocytoma-related cardiomyopathy:
      inverted Takotsubo contractile pattern.

PMID- 16651481
TI  - Cardiology education in Bosnia and Herzegovina.

PMID- 16651482
TI  - Akt signaling and growth of the heart.

PMID- 16651483
TI  - The forgotten lymphocyte: immunity and stroke.

PMID- 16651484
TI  - Is C-reactive protein an innocent bystander or proatherogenic culprit? The
      verdict is still out.

PMID- 16651486
TI  - Returning to the basics: a new era in pediatric education.

PMID- 16651487
TI  - Pediatric organ transplantation needs: organ donation best practices.

PMID- 16651488
TI  - Estimate of the commercial value of underage drinking and adult abusive and
      dependent drinking to the alcohol industry.
AB  - OBJECTIVES: To document quantity and cash value of underage and adult Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined
      abusive and dependent drinking as well as underage drinking and adult DSM-IV
      defined abusive and dependent drinking combined to the alcohol industry. DESIGN:
      Analysis of multiple cross-sectional national data sets. SETTING: The 2001
      National Household Survey on Drug Abuse, the 2001 Youth Risk Behavior Survey, the
      2001 Behavioral Risk Factor Surveillance Survey, the 2000 US Census, the 2000 to
      2001 National Epidemiological Survey on Alcohol and Related Conditions, and the
      2001 Adams Business Research. PARTICIPANTS: A total of 260,580 persons aged 12
      years and older across 4 data sources. MAIN EXPOSURE: Underage drinking or
      pathological drinking defined as meeting the DSM-IV criteria for abusive or
      dependent drinking. MAIN OUTCOME MEASURES: Total amount of alcohol consumed and
      the cash value for alcohol consumed among underage and adult drinkers with DSM-IV
      defined alcohol abuse and dependence as well as all underage drinkers combined
      with adult drinkers with DSM-IV-defined alcohol abuse and dependence. RESULTS:
      The short-term cash value of underage drinking to the alcohol industry was 22.5
      billion dollars in 2001-17.5% of total consumer expenditures for alcohol. The
      long-term commercial value of underage drinking is the contribution of underage
      drinking to maintaining consumption among adult drinkers with alcohol abuse and
      dependence, which was equal to at least 25.8 billion dollars in 2001.
      CONCLUSIONS: The combined value of illegal underage drinking and adult
      pathological drinking to the industry was at least 48.3 billion dollars, or 37.5%
      of consumer expenditures for alcohol, in 2001. Alternative estimates suggest that
      these costs may be closer to 62.9 billion dollars, or 48.8% of consumer
      expenditures for alcohol.

PMID- 16651489
TI  - Patterns and knowledge of nonmedical use of stimulants among college students.
AB  - OBJECTIVE: To determine patterns and knowledge of nonmedical use of stimulants
      among a sample of college students. DESIGN: Completion of an anonymous survey
      consisting of 23 questions designed to explore college student use of medications
      intended to treat attention-deficit/hyperactivity disorder. SETTING: A private
      liberal arts college in New England. PARTICIPANTS: Three hundred forty-seven
      undergraduate students. MAIN OUTCOME MEASURE: Nonmedical use of stimulants.
      RESULTS: Thirty-one students (9.2%) reported nonmedical stimulant use. Two
      hundred forty students (71.4%) had peers who used nonprescribed stimulants, 149
      (44.3%) knew of peers who made stimulant medication-seeking visits to a physician
      although they did not believe that they had attention-deficit/hyperactivity
      disorder, and 178 (53.0%) knew of people who sold stimulants to students.
      Nonprescription users were significantly more knowledgeable about the effects of
      stimulants than nonusers, and nonusers whose peers used nonprescribed stimulants
      were more knowledgeable about the effects of stimulants than nonusers whose peers
      did not use nonprescribed stimulants. After controlling for age, race, and sex,
      the variables that predicted nonmedical use of stimulants were beliefs that
      stimulants help individuals study better, stay awake, and lose weight.
      CONCLUSIONS: A substantial proportion of college students in this sample were
      using nonprescribed stimulants. Among nonusers, those whose peers use
      nonprescribed stimulants were much more knowledgeable about the effects of
      stimulant use than those whose peers do not use stimulants. This knowledge may
      confer an increased risk of future nonmedical stimulant use if students become
      tempted to seek the beneficial effects experienced by their peers.

PMID- 16651490
TI  - Pediatricians' clinical decision making: results of 2 randomized controlled
      trials of test performance characteristics.
AB  - OBJECTIVE: To determine whether presenting test performance characteristics
      influences clinical management. DESIGN: Two questionnaire-based, randomized
      controlled trials. SETTING: Mailed surveys with 2 clinical vignettes.
      PARTICIPANTS: Randomly selected US pediatricians (N=1502). INTERVENTION: Vignette
      specific, randomly assigned test information: no additional information
      (control), test characteristics (TC), or TC defined. In the pertussis vignette,
      the TC group received the direct fluorescent antibody test's sensitivity and
      specificity, and the TC defined group received the same information with
      definitions. In the urinalysis vignette, the TC group received the false-positive
      rate of persistent microhematuria in predicting renal disease, and the TC defined
      group received a definition of this information. MAIN OUTCOME MEASURES: In the
      pertussis vignette, diagnostic test choice and management of erythromycin therapy
      and hospital discharge plans. In the urinalysis vignette, serum laboratory
      testing and nephrology referral plans. RESULTS: Six hundred fifty-three
      participants (49.5% of those eligible) returned completed surveys. In the
      pertussis vignette, significantly more of the TC (73%) and TC defined (71%)
      groups ordered the best-performing test than did controls (21%) (P<.001 for both
      comparisons). Receiving test characteristics did not significantly affect
      erythromycin therapy or hospital discharge plans (P>or=.40). In the urinalysis
      vignette, the TC defined group referred to nephrology (30%) and checked
      laboratory tests (88%) significantly more often than did controls (19%, P=.01;
      78%, P=.01, respectively), but the TC and control groups' testing and referral
      plans did not differ significantly (22% vs 19%, P=.36; 75% vs 78%, P=.48,
      respectively). CONCLUSION: Providing test performance characteristics influenced
      certain clinical decisions, sometimes in unexpected ways.

PMID- 16651491
TI  - Error reduction in pediatric chemotherapy: computerized order entry and failure
      modes and effects analysis.
AB  - OBJECTIVE: To implement and evaluate the impact of computerized provider order
      entry (CPOE) on reducing ordering errors in pediatric chemotherapy. DESIGN:
      Before-and-after study from 2001 to 2004. SETTING: Pediatric Oncology in an
      academic medical center. INTERVENTION: Implementation of a CPOE system guided by
      multidisciplinary failure modes and effects analysis into pediatric chemotherapy.
      MAIN OUTCOME MEASURES: Completion data on chemotherapy steps of high
      morbidity/mortality potential if missed (as determined by attending oncologists)
      from 1259 pre-CPOE paper and 1116 post-CPOE pediatric chemotherapy orders.
      RESULTS: After CPOE deployment, daily chemotherapy orders were less likely to
      have improper dosing (relative risk [RR], 0.26; 95% confidence interval [CI],
      0.11-0.61), incorrect dosing calculations (RR, 0.09; 95% CI, 0.03-0.34), missing
      cumulative dose calculations (RR, 0.32; 95% CI, 0.14-0.77), and incomplete
      nursing checklists (RR, 0.51; 95% CI, 0.33-0.80). There was no difference in the
      likelihood of improper dosing on treatment plans and a higher likelihood of not
      matching medication orders to treatment plans (RR, 5.4; 95% CI, 3.1-9.5).
      CONCLUSION: Failure modes and effects analysis-guided CPOE reduced ordering
      errors in pediatric chemotherapy and provided data for further improvements.

PMID- 16651492
TI  - Picture of the month. Trichobezoar.

PMID- 16651493
TI  - Systematic review of the relationship between early introduction of solid foods
      to infants and the development of allergic disease.
AB  - OBJECTIVE: To assess the evidence that early solid feeding (before age 4 months)
      increases the risk of allergic disease. DATA SOURCES: MEDLINE, the Cochrane
      Library, and the Drugs and Pharmacology section of EMBASE with key words
      "infant," "food," and "allergy." STUDY SELECTION: We found 2719 article citations
      and reviewed references of relevant articles. We critically evaluated the methods
      and results of articles that met inclusion criteria. We identified 13 studies
      that met inclusion criteria. There was only 1 controlled trial. DATA EXTRACTION:
      Allergic disease. DATA SYNTHESIS: Five studies found a positive association
      between early solid feeding and eczema, with a persistence of the association for
      10 years in 1 study. Four studies found no association. One study found an
      association between early solid feeding and pollen allergy. We found no strong
      evidence to support the association between early solid feeding and the
      development of persistent asthma, persistent food allergy, allergic rhinitis, or
      animal dander allergy. CONCLUSIONS: Systematic review of available evidence
      suggests that early solid feeding may increase the risk of eczema. However, there
      are little data supporting an association between early solid feeding and other
      allergic conditions. Since many studies had problematic methods, additional
      controlled trials are needed to help guide physicians as they advise parents
      about the allergic risks of early introduction of solids.

PMID- 16651494
TI  - Excessive crying beyond 3 months may herald other features of multiple regulatory
      problems.
AB  - OBJECTIVE: To assess duration of excessive crying and its relation to sleep and
      eating disturbances in a population sample of infants. DESIGN: Cross-sectional
      study. SETTING: Random digit-dialing survey, enrolling birth cohorts between 1999
      and 2003, in Germany. PARTICIPANTS: Children aged 4 years and younger. MAIN
      EXPOSURES: Excessive crying, retrospectively ascertained according to modified
      Wessel's criteria, and duration of excessive crying. MAIN OUTCOME MEASURES:
      Severe eating or sleeping problems at interview. RESULTS: The participation rate
      in the random digit-dialing survey was 62%. The analysis was confined to 1865
      children with complete data. The observed prevalence for excessive crying ever
      was 16.3% (95% confidence interval [CI], 14.7-18.1), beyond 3 months 5.8% (95%
      CI, 4.8-6.9), and beyond 6 months 2.5% (95% CI, 1.9-3.3). Excessive crying only
      in the first 3 months did not increase the prevalence of sleep or eating
      disturbances whereas crying beyond 6 months did; prevalence of eating disorders
      was 19.1% (95% CI, 9.1-33.3) and prevalence of sleeping disorders was 12.8% (95%
      CI, 4.8-25.7) compared with 2.7% (95% CI, 1.9-3.6) and 3.6% (95% CI, 2.7-4.6),
      respectively, in children without excessive crying. CONCLUSIONS: Persistence of
      crying beyond the first 6 months heralded a higher prevalence of eating or
      sleeping difficulties in children with excessive crying than in children without
      excessive crying. These parents should be offered support and counseling over a
      broader spectrum of features related to multiple regulatory problems.

PMID- 16651495
TI  - Maternal infant-feeding style and children's adiposity at 5 years of age.
AB  - OBJECTIVES: To examine the relationship between maternal infant-feeding style and
      adiposity in childhood and to determine whether feeding style explains any of the
      association between maternal obesity and childhood adiposity. DESIGN: Prospective
      cohort study. SETTING: Cincinnati metropolitan area. PARTICIPANTS: A total of 313
      preschool children; 80% were white and 20% were black. MAIN OUTCOME MEASURES:
      Seven factors describing maternal infant-feeding style derived from the Infant
      Feeding Questionnaire administered at age 3 years; maternal obesity, defined as a
      body mass index of 30 or higher before pregnancy; and adiposity at 5 years of age
      as assessed by dual-energy x-ray absorptiometry. RESULTS: The mean +/- SD fat
      mass was 4.55 +/- 1.64 kg. Seventeen percent of the mothers were obese before
      pregnancy. Children whose mothers had high concern about the infant overeating or
      becoming overweight (the highest tertile of the "overeating" factor) had 0.67 kg
      (95% confidence interval, 0.31-1.03 kg) higher fat mass than children whose
      mothers did not have high concern (the other 2 tertiles). None of the other 6
      feeding factors were related to childhood adiposity. Children of obese mothers
      had 0.54 kg (95% confidence interval, 0.10-0.98 kg) higher fat mass than children
      of nonobese mothers. High concern about the infant overeating, which was more
      common in obese mothers, accounted for 15% of this 0.54-kg difference.
      CONCLUSION: High maternal concern about an infant overeating or becoming
      overweight was associated with higher adiposity at 5 years of age and explained
      some of the association between maternal obesity and child adiposity.

PMID- 16651496
TI  - Prevalence of diabetes and impaired fasting glucose levels among US adolescents:
      National Health and Nutrition Examination Survey, 1999-2002.
AB  - OBJECTIVE: To determine the current prevalence of self-reported diabetes and
      impaired fasting glucose levels among US adolescents. DESIGN AND SETTING: Cross
      sectional, National Health and Nutrition Examination Survey (1999-2002).
      PARTICIPANTS: A sample of 4370 adolescents (aged 12-19 years) with self-reported
      diabetes and a subsample of 1496 adolescents without self-reported diabetes who
      had fasted for at least 8 hours. Subjects who reported having diabetes and using
      insulin were further categorized as having type 1 diabetes, those reporting
      having diabetes and not using insulin as having type 2 diabetes, and those with a
      fasting plasma glucose level greater than or equal to 5.6 mmol/L (100 mg/dL) as
      having impaired fasting glucose levels. MAIN OUTCOME MEASURES: Prevalence of self
      reported diabetes, type 1 and type 2 diabetes, and impaired fasting glucose
      levels among US adolescents. RESULTS: In the full sample, 0.5% (95% confidence
      interval [CI], 0.24%-0.76%) of adolescents reported having diabetes. Of those
      reporting diabetes, roughly 71% (95% CI, 56%-86%) were categorized as having type
      1 and 29% (95% CI, 14%-44%) as having type 2 diabetes. In the subsample, roughly
      11% (95% CI, 8%-14%) had impaired fasting glucose levels. Using population-based
      sample weights, these proportions were equivalent to 39 005 US adolescents with
      type 2 diabetes and 2 769 736 with impaired fasting glucose levels. CONCLUSIONS:
      The prevalence of type 2 diabetes and impaired fasting glucose levels is
      substantial among US adolescents. These estimates have important implications for
      public health because of the high rate of conversion from impaired fasting
      glucose level to type 2 diabetes in adults and the increased risk of
      cardiovascular disease in individuals with type 2 diabetes.

PMID- 16651497
TI  - Genetic testing of minors for alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Alpha(1)-antitrypsin deficiency (AATD) is a genetic disorder
      primarily affecting the lungs and liver of affected individuals, causing severe
      panlobular emphysema and cirrhosis. OBJECTIVE: To describe the demographics and
      feasibility of a home test for AATD in children and adolescents. DESIGN: Case
      series of parents who test their children for AATD. SETTING: Nonprofit supported
      program in which participants telephoned or e-mailed requests for alpha(1)
      antitrypsin testing. PARTICIPANTS: All persons younger than 18 years whose
      parents or guardians chose to test for AATD from January 1, 2002, to October 1,
      2004. INTERVENTIONS: Home-administered finger-stick blood spot test for alpha(1)
      antitrypsin genotype and questionnaire. MAIN OUTCOME MEASURES: The alpha(1)
      antitrypsin genotypes and questionnaire responses. RESULTS: The Alpha Coded
      Testing Study tested 422 children and adolescents with a confidential test for
      AATD. Testing was suggested by a family member in most (76.7%) of the cases and
      was responsible for the many carrier (PIMZ and PIMS) genotypes (51.9%) in the
      study. Interest in testing was equally distributed among all ages. Test
      confidentiality was seen as an important reason to test (64.1% with a Likert
      scale score of 4-5 on a 5-point scale). Parents and guardians of the minors
      suggested that testing benefits (mean [SD] Likert score, 3.5 [1.4] on a 5-point
      scale) were higher than risks (mean [SD] Likert score, 1.7 [1.2]) (P=.001).
      CONCLUSION: Parents value genetic testing of their children at risk for AATD when
      testing can be done in a confidential setting.

PMID- 16651498
TI  - Improved asthma outcomes in a high-morbidity pediatric population: results of an
      emergency department-based randomized clinical trial.
AB  - OBJECTIVE: To determine if an emergency department-based asthma follow-up clinic
      could improve outcomes within a high-morbidity pediatric population. DESIGN:
      Prospective, randomized clinical trial with 6 months of follow-up. SETTING:
      Emergency department of an urban pediatric medical center. PARTICIPANTS:
      Convenience sample of 488 patients aged 12 months to 17 years, inclusive, with
      prior physician-diagnosed asthma and 1 or more other unscheduled visits in the
      previous 6 months and/or 1 or more hospitalizations in the prior 12 months.
      INTERVENTION: Single follow-up clinic visit focusing on 3 domains: asthma self
      monitoring and management, environmental modification and trigger control, and
      linkages and referrals to ongoing care. MAIN OUTCOME MEASURES: The primary
      outcome measure was unscheduled visits for acute asthma care. Secondary outcomes
      included compliance with a medical plan and asthma quality of life. Analysis was
      by intention to treat with adjustment for baseline differences. RESULTS: Of those
      randomized to the clinic visit, 172 (70.5%) of 244 attended. The intervention
      group had significantly fewer mean unscheduled visits for asthma care during
      follow-up (1.39 vs 2.34; relative risk [RR] = 0.60 [95% confidence interval (CI),
      0.46-0.77]). At 6 months, significantly more patients in the intervention group
      reported use of inhaled corticosteroids in the prior 2 days (49.3% vs 26.5%; RR =
      2.03 [95% CI, 1.57-2.62]), no limitation in daytime quality of life (43.8% vs
      34.4%; RR = 1.36 [95% CI, 1.06-1.73]), and no functional limitations in quality
      of life (49.8% vs 40.8%; RR = 1.33 [95% CI, 1.08-1.63]). CONCLUSION: Attendance
      in the follow-up clinic was high. The intervention decreased subsequent
      unscheduled health care use while improving compliance and quality of life.

PMID- 16651499
TI  - Parental misperceptions about children and firearms.
AB  - OBJECTIVE: To assess the accuracy of parental predictions about their children's
      self-reported behavior around household guns. DESIGN: Survey. SETTING: Family
      practice clinic in rural Alabama. PARTICIPANTS: Convenience sample of parents and
      their children aged 5 to 14 years. INTERVENTION: Questionnaires about firearms
      administered separately to children and their parents. MAIN OUTCOME MEASURES:
      Rates of concordance and discordance between parents and their children living in
      homes with guns about whether the children knew the storage location of household
      firearms and had ever handled firearms in the home. RESULTS: Of 420 parent-child
      dyads, 314 agreed to participate; 201 of the 314 homes contained guns. Children
      younger than 10 years were as likely as older children to report knowing the
      storage location (73% vs 79%, respectively) and to report having handled a
      household gun (36% vs 36%, respectively). Thirty-nine percent of parents who
      reported that their children did not know the storage location of household guns
      and 22% of parents who reported that their children had never handled a household
      gun were contradicted by their children's reports. Such discordance between
      parent and child reports was unrelated to whether parents stored their firearms
      locked away or had ever discussed firearm safety with their children.
      CONCLUSIONS: Many parents who were living in homes with firearms and who reported
      that their children had never handled firearms in their homes were contradicted
      by their children's self-reports. Parents who locked their guns away and
      discussed gun safety with their children were as likely to be contradicted as
      parents who did not take such safety measures.

PMID- 16651500
TI  - Meeting the need for transplantable organs through the US donation system.

PMID- 16651502
TI  - Implications for primary care of diabetes and impaired fasting glucose prevalence
      in adolescents.

PMID- 16651503
TI  - Prospects for the prevention of allergy: a losing battle or a battle still worth
      fighting?

PMID- 16651504
TI  - Napoleon Bonaparte visiting the plague-stricken at Jaffa.

PMID- 16651505
TI  - Caution regarding the use of pilot studies to guide power calculations for study
      proposals.
AB  - Clinical researchers often propose (or review committees demand) pilot studies to
      determine whether a study is worth performing and to guide power calculations.
      The most likely outcomes are that (1) studies worth performing are aborted and
      (2) studies that are not aborted are underpowered. There are many excellent
      reasons for performing pilot studies. The argument herein is not meant to
      discourage clinical researchers from performing pilot studies (or review
      committees from requiring them) but simply to caution against their use for the
      objective of guiding power calculations.

PMID- 16651506
TI  - A national study of violent behavior in persons with schizophrenia.
AB  - CONTEXT: Violent behavior is uncommon, yet problematic, among schizophrenia
      patients. The complex effects of clinical, interpersonal, and social
      environmental risk factors for violence in this population are poorly understood.
      OBJECTIVE: To examine the prevalence and correlates of violence among
      schizophrenia patients living in the community by developing multivariable
      statistical models to assess the net effects of psychotic symptoms and other risk
      factors for minor and serious violence. DESIGN: A total of 1410 schizophrenia
      patients were clinically assessed and interviewed about violent behavior in the
      past 6 months. Data comprise baseline assessments of patients enrolled in the
      National Institute of Mental Health Clinical Antipsychotic Trials of Intervention
      Effectiveness. SETTING AND PATIENTS: Adult patients diagnosed as having
      schizophrenia were enrolled from 56 sites in the United States, including
      academic medical centers and community providers. MAIN OUTCOME MEASURES: Violence
      was classified at 2 severity levels: minor violence, corresponding to simple
      assault without injury or weapon use; and serious violence, corresponding to
      assault resulting in injury or involving use of a lethal weapon, threat with a
      lethal weapon in hand, or sexual assault. A composite measure of any violence was
      also analyzed. RESULTS: The 6-month prevalence of any violence was 19.1%, with
      3.6% of participants reporting serious violent behavior. Distinct, but
      overlapping, sets of risk factors were associated with minor and serious
      violence. "Positive" psychotic symptoms, such as persecutory ideation, increased
      the risk of minor and serious violence, while "negative" psychotic symptoms, such
      as social withdrawal, lowered the risk of serious violence. Minor violence was
      associated with co-occurring substance abuse and interpersonal and social
      factors. Serious violence was associated with psychotic and depressive symptoms,
      childhood conduct problems, and victimization. CONCLUSIONS: Particular clusters
      of symptoms may increase or decrease violence risk in schizophrenia patients.
      Violence risk assessment and management in community-based treatment should focus
      on combinations of clinical and nonclinical risk factors.

PMID- 16651507
TI  - Long-term effectiveness and cost of a systematic care program for bipolar
      disorder.
AB  - CONTEXT: Despite the availability of efficacious treatments, the long-term course
      of bipolar disorder is often unfavorable. OBJECTIVE: To test the effectiveness of
      a multicomponent intervention program to improve the quality of care and long
      term outcomes for persons with bipolar disorder. DESIGN: Randomized controlled
      trial with allocation concealment and blinded outcome assessment. SETTING: Mental
      health clinics of a group-model prepaid health plan. PATIENTS: Of 785 patients in
      treatment for bipolar disorder who were invited to participate, 509 attended an
      evaluation appointment, 450 were found eligible to participate, and 441 enrolled
      in the trial. INTERVENTIONS: Participants were randomly assigned to a
      multicomponent intervention program or to continued care as usual. Three nurse
      care managers provided a 2-year systematic intervention program, including the
      following: a structured group psychoeducational program, monthly telephone
      monitoring of mood symptoms and medication adherence, feedback to treating mental
      health providers, facilitation of appropriate follow-up care, and as-needed
      outreach and crisis intervention. MAIN OUTCOME MEASURES: In-person blinded
      research interviews every 3 months assessed mood symptoms using the Longitudinal
      Interval Follow-up Examination. Health plan administrative records were used to
      assess the use and cost of mental health services. RESULTS: Intent-to-treat
      analyses demonstrated that the intervention significantly reduced the mean level
      of mania symptoms (z = 2.09, P = .04) and the time with significant mania
      symptoms (19.2 vs 24.7 weeks; F(1) = 6.0, P = .01). There was no significant
      intervention effect on mean level of depressive symptoms (z = 0.19, P = .85) or
      time with significant depressive symptoms (47.6 vs 50.7 weeks; F(1) = 0.56, P =
      .45). Benefits of the intervention were found only in a subgroup of 343 persons
      with clinically significant mood symptoms at the baseline assessment. The
      incremental cost (adjusted) of the intervention was 1251 dollars (95% confidence
      interval, 55-2446 dollars), including approximately 800 dollars for the
      intervention program services and an approximate 500 dollars increase in the
      costs of other mental health services. CONCLUSIONS: Population-based systematic
      care programs can significantly reduce the frequency and severity of mania in
      bipolar disorder, and cost increases are modest considering the clinical gains.
      The incorporation of more specific cognitive and behavioral content or more
      effective medication regimens may be necessary to significantly reduce the
      symptoms of depression.

PMID- 16651508
TI  - Major depressive episodes and random mood.
AB  - CONTEXT: Mathematical models describing changes in mood in affective disorders
      may assist in the identification of underlying pathologic and neurobiologic
      mechanisms and in differentiating between alternative interpretations of
      psychiatric data. OBJECTIVE: Using time-to-event data from a large epidemiologic
      survey on recovery from major depression, to model the survival probability, in
      terms of an underlying process, with parameters which might be recognized and
      influenced in clinical practice. DESIGN: We present a sequential-phase model for
      survival analysis, which describes depression as a state with or without an
      additional incubation phase. Recovery is seen as the transition to a
      nondepressive state. We show that this sequential-phase model finds a microscopic
      realization in a dynamic description, the random-mood model, which depicts mood
      as governed by an Ornstein-Uhlenbeck type of stochastic process, driven by
      intermittent gaussian noise. RESULTS: For reversible depression (80%), the
      fractional probability of recovery is remarkably independent of the history of
      the depression. Analysis with the sequential-phase model suggests single
      exponential decay in this group, possibly with a short incubation phase. Within
      the random-mood model, the data for this reversibly depressed cohort are
      compatible with an intermittent noise pattern of stimuli with average spacing of
      4 months and incompatible with nonintermittent noise. CONCLUSIONS: Time-to-event
      data from psychiatric epidemiologic studies can be conceptualized through
      modeling as intrasubject processes. The proposed random-mood model reproduces the
      time-to-event data and explains the incubation phase as an artifact due to the
      inclusion criterion of 14 days in most current psychiatric diagnostic systems.
      Depression is found to result more often from pileup of negative stimuli than
      from single life events. Time sequences, generated using the random-mood model,
      produce power plots, phase-space trajectories, and pair-correlation sums, similar
      to recent results for individual patients. This suggests possible clinical
      relevance along with the model's use as a tool in survival analysis.

PMID- 16651509
TI  - Sertraline for prevention of depression recurrence in diabetes mellitus: a
      randomized, double-blind, placebo-controlled trial.
AB  - CONTEXT: In patients with diabetes mellitus, depression is a prevalent and
      recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To
      determine whether maintenance therapy with sertraline hydrochloride prevents
      recurrence of major depression in patients with diabetes. DESIGN: A randomized,
      double-blind, placebo-controlled, maintenance treatment trial. Patients who
      recovered from depression during open-label sertraline treatment continued to
      receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52
      weeks or until depression recurred. SETTING: Outpatient clinics at Washington
      University, St Louis, MO, the University of Washington, Seattle, and the
      University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with
      diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who
      recovered from major depression (43.3% of those initially assigned) during 16
      weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d).
      INTERVENTION: Sertraline continued at recovery dose or identical-appearing
      placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured
      as the number of days after randomization) to recurrence of major depression as
      defined in DSM-IV. The secondary outcome was glycemic control, which was assessed
      via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline
      conferred significantly greater prophylaxis against depression recurrence than
      did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02).
      Elapsed time before major depression recurred in one third of the patients
      increased from 57 days in patients who received placebo to 226 days in patients
      treated with sertraline. Glycosylated hemoglobin levels decreased during the open
      treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/-
      1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than
      baseline during depression-free maintenance (P = .002) and did not differ between
      treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance
      therapy with sertraline prolongs the depression-free interval following recovery
      from major depression. Depression recovery with sertraline as well as sustained
      remission with or without treatment are associated with improvements in
      glycosylated hemoglobin levels for at least 1 year.

PMID- 16651510
TI  - Depression and risk for Alzheimer disease: systematic review, meta-analysis, and
      metaregression analysis.
AB  - CONTEXT: A history of depression may increase risk for developing Alzheimer
      disease (AD) later in life. Clarifying this relation might improve understanding
      of risk factors for and disease mechanisms in AD. OBJECTIVE: To systematically
      review and complete a meta-analysis on the relation of depression and AD. DATA
      SOURCES: We conducted electronic bibliographic searches of MEDLINE, PsychLit,
      EMBASE, and BIOSIS using search terms sensitive to studies of etiology combined
      with searches on terms related to depression and AD and reviewed reference lists
      of articles. STUDY SELECTION: Studies with data contrasting depressed vs
      nondepressed patients who did and did not later develop AD were included. Studies
      that related continuous measures of depression and cognitive status were
      excluded. DATA EXTRACTION: Numerical data were independently extracted by 3
      reviewers. They also rated studies on a scale that assessed quality indicators
      for observational studies. Data on the interval between observation of depression
      and the diagnosis of AD were collected when available. DATA SYNTHESIS: Meta
      analytic evaluation with random-effects models resulted in pooled odds ratios of
      2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95%
      confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk
      were robust to sensitivity analyses. Interval between diagnoses of depression and
      AD was positively related to increased risk of developing AD, suggesting that
      rather than a prodrome, depression may be a risk factor for AD. CONCLUSIONS: A
      history of depression may confer an increased risk for later developing AD. This
      relation may reflect an independent risk factor for the disease.

PMID- 16651511
TI  - Longitudinal mapping of cortical thickness and clinical outcome in children and
      adolescents with attention-deficit/hyperactivity disorder.
AB  - CONTEXT: Data from a previous prospective study of lobar volumes in children with
      attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of
      cortical thickness. OBJECTIVE: To determine whether regional differences in
      cortical thickness or cortical changes across time characterize ADHD and predict
      or reflect its clinical outcome. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal
      study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls
      recruited mainly from a local community in Maryland. Participants were assessed
      with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or
      more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7
      years). MAIN OUTCOME MEASURES: Cortical thickness across the cerebrum. Patients
      with ADHD were divided into better and worse outcome groups on the basis of a
      mean split in scores on the Children's Global Assessment Scale and
      persistence/remission of DSM-IV-defined ADHD. RESULTS: Children with ADHD had
      global thinning of the cortex (mean reduction, -0.09 mm; P=.02), most prominently
      in the medial and superior prefrontal and precentral regions. Children with worse
      clinical outcome had a thinner left medial prefrontal cortex at baseline than the
      better outcome group (-0.38 mm; P=.003) and controls (-0.25 mm; P=.002). Cortical
      thickness developmental trajectories did not differ significantly between the
      ADHD and control groups throughout except in the right parietal cortex, where
      trajectories converged. This normalization of cortical thickness occurred only in
      the better outcome group. CONCLUSIONS: Children with ADHD show relative cortical
      thinning in regions important for attentional control. Children with a worse
      outcome have "fixed" thinning of the left medial prefrontal cortex, which may
      compromise the anterior attentional network and encumber clinical improvement.
      Right parietal cortex thickness normalization in patients with a better outcome
      may represent compensatory cortical change.

PMID- 16651512
TI  - Maternal mental health, substance use, and domestic violence in the year after
      delivery and subsequent behavior problems in children at age 3 years.
AB  - CONTEXT: Mental health disorders, substance use, and domestic violence often
      occur together. However, studies examining the impact of these conditions in
      mothers on the well-being of their children have focused only on isolated
      conditions. OBJECTIVE: To examine the cumulative effect of maternal mental health
      disorders, substance use, and domestic violence on the risk of behavior problems
      in young children. DESIGN: A birth cohort (1998-2000) followed up to age 3 years.
      SETTING: Eighteen large US cities. PARTICIPANTS: At 3 years, 2756 (65%) were
      followed up from the population-based birth cohort of 4242. Thirty-six percent
      had annual incomes below the poverty threshold. MAIN OUTCOME MEASURES: One year
      after delivery, mothers were asked questions about conditions in 3 categories:
      (1) mental health (major depressive episode and generalized anxiety disorder),
      (2) substance use (smoking, binge drinking, and illicit drug use), and (3)
      domestic violence (emotional and physical). At 3 years, mothers completed
      questions from the Child Behavior Checklist. RESULTS: Fifty percent of mothers
      had a condition in at least 1 of the 3 categories. The prevalence of child
      behavior problems increased with the number of categories (0, 1, 2, or 3) in
      which the mother reported a condition: respectively, 7%, 12%, 17%, and 19% for
      aggression (P<.001); 9%, 14%, 16%, and 27% for anxious/depressed (P<.001); and
      7%, 12%, 15%, and 19% for inattention/hyperactivity (P<.001). This graded risk
      persisted after adjustment for sociodemographic and prenatal factors and for
      paternal mental health and substance use. CONCLUSIONS: The risk of child behavior
      problems increased with the number of areas--mental health, substance use, or
      domestic violence--in which the mother reported difficulties. Preventing behavior
      problems in young children requires family-oriented strategies that address the
      needs of both parents and their children.

PMID- 16651513
TI  - Prediction of early-onset deviant peer group affiliation: a 12-year longitudinal
      study.
AB  - CONTEXT: Deviant peer group involvement is strongly related to onset,
      aggravation, and persistence of conduct problems during adolescence. OBJECTIVE:
      To identify early childhood behavioral profiles that predict early-onset deviant
      peer group involvement. DESIGN: A 12-year longitudinal study of behavioral
      development. SETTING: Fifty-three inner-city elementary schools in a large
      Canadian city. PARTICIPANTS: A total of 1037 boys in kindergarten from low
      socioeconomic neighborhoods. MAIN OUTCOME MEASURES: Annual self-reported deviant
      peer group involvement from 11 to 17 years of age. RESULTS: Kindergarten boys
      were at highest risk of following an early adolescence trajectory of deviant peer
      group affiliation if they were hyperactive, fearless, and low on prosocial
      behaviors but much less at risk if they scored high on only 2 of these
      dimensions. Family adversity had no main effect but substantially increased the
      risk of following an early adolescence trajectory of deviant peer group
      affiliation for boys with a profile of hyperactivity, fearlessness, and low
      prosocial behaviors. CONCLUSIONS: Kindergarten boys from low socioeconomic areas
      who are hyperactive, fearless, infrequently prosocial, and raised in adverse
      family environments are at much heightened risk of engaging in deviant peer
      groups early in their development. Boys at high risk can be identified as early
      as kindergarten and should be targeted for preventive intervention.

PMID- 16651514
TI  - Subtle neurologic compromise as a vulnerability factor for combat-related
      posttraumatic stress disorder: results of a twin study.
AB  - CONTEXT: Previous studies have demonstrated subtle neurologic dysfunction in
      chronic posttraumatic stress disorder (PTSD) manifest as increased neurologic
      soft signs (NSSs). The origin of this dysfunction is undetermined. OBJECTIVE: To
      resolve competing origins of increased NSSs in PTSD, namely, preexisting
      vulnerability factor vs acquired PTSD sign. DESIGN: Case-control study of
      identical twins. SETTING: A Veterans Affairs and academic medical center
      (ambulatory). PARTICIPANTS: A convenience sample of male Vietnam veteran twins
      with (n = 25) and without (n = 24) PTSD and their combat-unexposed identical
      (monozygotic) co-twins. INTERVENTIONS: Neurologic examination for 45 NSSs. MAIN
      OUTCOME MEASURE: Average scores for 45 NSSs, each scored on an ordinal scale from
      0 to 3, masked to diagnosis and combat exposure status. RESULTS: There was a
      significant between-pair main effect of PTSD diagnosis (as determined in the
      combat-exposed twin) on average NSS score in the absence of a significant combat
      exposure main effect or diagnosis x exposure interaction. Combat veterans with
      PTSD had significantly higher NSS scores than combat veterans without PTSD. The
      "high-risk," unexposed co-twins of the former also had significantly higher NSS
      scores than the "low-risk," unexposed co-twins of the latter. This result could
      not be explained by age, number of potentially traumatic lifetime noncombat
      events, alcoholism, or the presence of a comorbid affective or anxiety disorder.
      The average NSS score in unexposed co-twins was not significantly associated with
      combat severity in combat-exposed twins. CONCLUSIONS: These results replicate
      previous findings of increased NSSs in Vietnam combat veterans with PTSD.
      Furthermore, results from their combat-unexposed identical co-twins support the
      conclusion that subtle neurologic dysfunction in PTSD is not acquired along with
      the trauma or PTSD but rather represents an antecedent familial vulnerability
      factor for developing chronic PTSD on exposure to a traumatic event.

PMID- 16651515
TI  - Parenting behaviors associated with risk for offspring personality disorder
      during adulthood.
AB  - CONTEXT: Research has suggested that some types of parental child-rearing
      behavior may be associated with risk for offspring personality disorder (PD), but
      the association of parenting with offspring PD has not been investigated
      comprehensively with prospective longitudinal data. OBJECTIVE: To investigate the
      association of parental child-rearing behavior with risk for offspring PD during
      adulthood. DESIGN: The Children in the Community study, a prospective
      longitudinal investigation. SETTING AND PARTICIPANTS: A community-based sample of
      593 families interviewed during childhood (mean age, 6 years), adolescence (mean
      ages, 14 and 16 years), emerging adulthood (mean age, 22 years), and adulthood
      (mean age, 33 years) of the offspring. MAIN OUTCOME MEASURE: The Structured
      Clinical Interview for DSM-IV Personality Disorders. RESULTS: Ten types of
      parenting behavior that were evident during the child-rearing years were
      associated with elevated offspring risk for PD during adulthood when childhood
      behavioral or emotional problems and parental psychiatric disorders were
      controlled statistically. Parental behavior in the home during the child-rearing
      years was associated with elevated risk for offspring PD at mean ages of 22 and
      33 years. Risk for offspring PD at both assessments increased steadily as a
      function of the number of problematic parenting behaviors that were evident. Low
      parental affection or nurturing was associated with elevated risk for offspring
      antisocial (P = .003), avoidant (P = .01), borderline (P = .002), depressive (P =
      .02), paranoid (P = .002), schizoid (P = .046), and schizotypal (P<.001) PDs.
      Aversive parental behavior (eg, harsh punishment) was associated with elevated
      risk for offspring borderline (P = .001), paranoid (P = .004), passive-aggressive
      (P = .046), and schizotypal (P = .02) PDs. CONCLUSIONS: Parental behavior during
      the child-rearing years may be associated with risk for offspring PD that endures
      into adulthood. This risk may not be attributable to offspring behavioral and
      emotional problems or parental psychiatric disorder, and it may not diminish over
      time. Low parental nurturing and aversive parental behavior during child rearing
      may both be associated with elevated risk for offspring PDs.

PMID- 16651517
TI  - Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent
      transcriptional regulation by Runx3.
AB  - Regulation of gene expression by tissue-specific transcription factors involves
      both turning on and turning off transcription of target genes. Runx3, a runt
      domain transcription factor, regulates cell-intrinsic functions by activating and
      repressing gene expression in sensory neurons, dendritic cells (DC), and T cells.
      To investigate the mechanism of Runx3-mediated repression in an in vivo context,
      we generated mice expressing a mutant Runx3 lacking the C-terminal VWRPY, a motif
      required for Runx3 interaction with the corepressor Groucho/transducin-like
      Enhancer-of-split (TLE). In contrast with Runx3(-/-) mice, which displayed ataxia
      due to the death of dorsal root ganglia TrkC neurons, Runx3(VWRPY-/-) mice were
      not ataxic and had intact dorsal root ganglia neurons, indicating that ability of
      Runx3 to tether Groucho/TLE is not essential for neurogenesis. In the DC
      compartment, the mutant protein Runx3(VWRPY-) promoted normally developed skin
      Langerhans cells but failed to restrain DC spontaneous maturation, indicating
      that this latter process involves Runx3-mediated repression through recruitment
      of Groucho/TLE. Moreover, in CD8(+) thymocytes, Runx3(VWRPY-) up-regulated
      alphaE/CD103-like WT Runx3, whereas unlike wild type, it failed to repress
      alphaE/CD103 in CD8(+) splenocytes. Thus, in CD8-lineage T cells, Runx3 regulates
      alphaE/CD103 in opposing regulatory modes and recruits Groucho/TLE to facilitate
      the transition from activation to repression. Runx3(VWRPY-) also failed to
      mediate the epigenetic silencing of CD4 gene in CD8(+) T cells, but normally
      regulated other pan-CD8(+) T cell genes. These data provide evidence for the
      requirement of Groucho/TLE for Runx3-mediated epigenetic silencing of CD4 and
      pertain to the mechanism through which other Runx3-regulated genes are
      epigenetically silenced.

PMID- 16651518
TI  - Post-Miocene expansion, colonization, and host switching drove speciation among
      extant nematodes of the archaic genus Trichinella.
AB  - Parasitic nematodes of the genus Trichinella cause significant food-borne illness
      and occupy a unique evolutionary position at the base of the phylum Nematoda,
      unlike the free-living nematode Caenorhabditis elegans. Although the forthcoming
      genome sequence of Trichinella spiralis can provide invaluable comparative
      information about nematode biology, a basic framework for understanding the
      history of the genus Trichinella is needed to maximize its utility. We therefore
      developed the first robust and comprehensive analysis of the phylogeny and
      biogeographic history of Trichinella using the variation in three genes (nuclear
      small-subunit rDNA, and second internal transcribed spacer, mitochondrial large
      subunit rDNA, and cytochrome oxidase I DNA) from all 11 recognized taxa. We
      conclude that (i) although Trichinellidae may have diverged from their closest
      extant relatives during the Paleozoic, all contemporary species of Trichinella
      diversified within the last 20 million years through geographic colonization and
      pervasive host switching among foraging guilds of obligate carnivores; (ii)
      mammalian carnivores disseminated encapsulated forms from Eurasia to Africa
      during the late Miocene and Pliocene, and to the Nearctic across the Bering Land
      Bridge during the Pliocene and Pleistocene, when crown species ultimately
      diversified; (iii) the greatest risk to human health is posed by those species
      retaining an ancestral capacity to parasitize a wide range of hosts; and (iv)
      early hominids may have first acquired Trichinella on the African savannah
      several million years before swine domestication as their diets shifted from
      herbivory to facultative carnivory.

PMID- 16651519
TI  - Loss of p53 impedes the antileukemic response to BCR-ABL inhibition.
AB  - Targeted cancer therapies exploit the continued dependence of cancer cells on
      oncogenic mutations. Such agents can have remarkable activity against some
      cancers, although antitumor responses are often heterogeneous, and resistance
      remains a clinical problem. To gain insight into factors that influence the
      action of a prototypical targeted drug, we studied the action of imatinib (STI
      571, Gleevec) against murine cells and leukemias expressing BCR-ABL, an imatinib
      target and the initiating oncogene for human chronic myelogenous leukemia (CML).
      We show that the tumor suppressor p53 is selectively activated by imatinib in BCR
      ABL-expressing cells as a result of BCR-ABL kinase inhibition. Inactivation of
      p53, which can accompany disease progression in human CML, impedes the response
      to imatinib in vitro and in vivo without preventing BCR-ABL kinase inhibition.
      Concordantly, p53 mutations are associated with progression to imatinib
      resistance in some human CMLs. Our results identify p53 as a determinant of the
      response to oncogene inhibition and suggest one way in which resistance to
      targeted therapy can emerge during the course of tumor evolution.

PMID- 16651520
TI  - A time-resolved vibrational spectroscopy glimpse into the oxygen-evolving complex
      of photosynthesis.

PMID- 16651521
TI  - Tracking germinal center B cells expressing germ-line immunoglobulin gamma1
      transcripts by conditional gene targeting.
AB  - Germinal centers (GCs) represent the main sites for the generation of high
      affinity, class-switched antibodies during T cell-dependent antibody responses.
      To study gene function specifically in GC B cells, we generated Cgamma1-cre mice
      in which the expression of Cre recombinase is induced by transcription of the Ig
      gamma1 constant region gene segment (Cgamma1). In these mice, Cre-mediated
      recombination at the fas, Igbeta, IgH, and Rosa26 loci occurred in GC B cells as
      early as 4 days after immunization with T cell-dependent antigens and involved
      >85% of GC B cells at the peak of the GC reaction. Less than 2% of IgM(+) B cells
      showed Cre-mediated recombination. These cells carried few Ig somatic mutations,
      expressed germ-line Cgamma1- and activation-induced cytidine deaminase-specific
      transcripts and likely include GC B cell founders and/or plasma cell precursors.
      Cre-mediated recombination involved most IgG1, but also a fraction of IgG3-,
      IgG2a-, IgG2b-, and IgA-expressing GC and post-GC B cells. This result indicates
      that a GC B cell can transcribe more than one downstream C(H) gene before
      undergoing class switch recombination. The efficient induction of Cre expression
      in GC B cells makes the Cgamma1-cre allele a powerful tool for the genetic
      analysis of these cells, as well as, in combination with a suitable marker for
      Cre-mediated recombination, the tracking of class-switched memory B and plasma
      cells in vivo. To expedite the genetic analysis of GC B cells, we have
      established Cgamma1-cre F(1) embryonic stem cells, allowing further rounds of
      gene targeting and the cloning of compound mutants by tetraploid embryo
      complementation.

PMID- 16651522
TI  - Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA
      genomes in human tissue.
AB  - Human erythrovirus is a minute, single-stranded DNA virus causing many diseases,
      including erythema infectiosum, arthropathy, and fetal death. After primary
      infection, the viral genomes persist in solid tissues. Besides the prototype,
      virus type 1, two major variants (virus types 2 and 3) have been identified
      recently, the clinical significance and epidemiology of which are mostly unknown.
      We examined 523 samples of skin, synovium, tonsil, or liver (birth year range,
      1913-2000), and 1,640 sera, by qualitative and quantitative molecular assays for
      the DNA of human erythroviruses. Virus types 1 and 2 were found in 132 (25%) and
      58 (11%) tissues, respectively. DNA of virus type 1 was found in all age groups,
      whereas that of type 2 was strictly confined to those subjects born before 1973
      (P < 0.001). Correspondingly, the sera from the past two decades contained DNA of
      type 1 but not type 2 or 3. Our data suggest strongly that the newly identified
      human erythrovirus type 2 as well as the prototype 1 circulated in Northern and
      Central Europe in equal frequency, more than half a century ago, whereafter type
      2 disappeared from circulation. Type 3 never attained wide occurrence in this
      area during the past > or =70 years. The erythrovirus DNA persistence in human
      tissues is lifelong and represents a source of information about our past, the
      Bioportfolio, which, at the individual level, provides a registry of one's
      infectious encounters, and at the population level, a database for
      epidemiological and phylogenetic analyses.

PMID- 16651523
TI  - CO(2) signaling in guard cells: calcium sensitivity response modulation, a Ca(2+)
      independent phase, and CO(2) insensitivity of the gca2 mutant.
AB  - Leaf stomata close in response to high carbon dioxide levels and open at low
      CO(2). CO(2) concentrations in leaves are altered by daily dark/light cycles, as
      well as the continuing rise in atmospheric CO(2). Relative to abscisic acid and
      blue light signaling, little is known about the molecular, cellular, and genetic
      mechanisms of CO(2) signaling in guard cells. Interestingly, we report that
      repetitive Ca(2+) transients were observed during the stomatal opening stimulus,
      low [CO(2)]. Furthermore, low/high [CO(2)] transitions modulated the cytosolic
      Ca(2+) transient pattern in Arabidopsis guard cells (Landsberg erecta).
      Inhibition of cytosolic Ca(2+) transients, achieved by loading guard cells with
      the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and
      not adding external Ca(2+), attenuated both high CO(2)-induced stomatal closing
      and low CO(2)-induced stomatal opening, and also revealed a Ca(2+)-independent
      phase of the CO(2) response. Furthermore, the mutant, growth controlled by
      abscisic acid (gca2) shows impairment in [CO(2)] modulation of the cytosolic
      Ca(2+) transient rate and strong impairment in high CO(2)-induced stomatal
      closing. Our findings provide insights into guard cell CO(2) signaling
      mechanisms, reveal Ca(2+)-independent events, and demonstrate that calcium
      elevations can participate in opposed signaling events during stomatal opening
      and closing. A model is proposed in which CO(2) concentrations prime Ca(2+)
      sensors, which could mediate specificity in Ca(2+) signaling.

PMID- 16651524
TI  - The brain-specific carnitine palmitoyltransferase-1c regulates energy
      homeostasis.
AB  - Fatty acid synthesis in the central nervous system is implicated in the control
      of food intake and energy expenditure. An intermediate in this pathway, malonyl
      CoA, mediates these effects. Malonyl-CoA is an established inhibitor of carnitine
      palmitoyltransferase-1 (CPT1), an outer mitochondrial membrane enzyme that
      controls entry of fatty acids into mitochondria and, thereby, fatty acid
      oxidation. CPT1c, a brain-specific enzyme with high sequence similarity to CPT1a
      (liver) and CPT1b (muscle) was recently discovered. All three CPTs bind malonyl
      CoA, and CPT1a and CPT1b catalyze acyl transfer from various fatty acyl-CoAs to
      carnitine, whereas CPT1c does not. These findings suggest that CPT1c has a unique
      function or activation mechanism. We produced a targeted mouse knockout (KO) of
      CPT1c to investigate its role in energy homeostasis. CPT1c KO mice have lower
      body weight and food intake, which is consistent with a role as an energy-sensing
      malonyl-CoA target. Paradoxically, CPT1c KO mice fed a high-fat diet are more
      susceptible to obesity, suggesting that CPT1c is protective against the effects
      of fat feeding. CPT1c KO mice also exhibit decreased rates of fatty acid
      oxidation, which may contribute to their increased susceptibility to diet-induced
      obesity. These findings indicate that CPT1c is necessary for the regulation of
      energy homeostasis.

PMID- 16651525
TI  - The infectious kiss: newly infected B cells deliver Epstein-Barr virus to
      epithelial cells.

PMID- 16651526
TI  - A unified theory for the basis of the limitations of the primary reaction of
      photosynthetic CO(2) fixation: was Dr. Pangloss right?

PMID- 16651527
TI  - Basic requirements for a metal-binding site in a protein: the influence of loop
      shortening on the cupredoxin azurin.
AB  - The main active-site loop of the copper-binding protein azurin (a cupredoxin) has
      been shortened from C(112)TFPGH(117)SALM(121) to C(112)TPH(115)PFM(118) (the
      native loop from the cupredoxin amicyanin) and also to C(112)TPH(115)PM(117). The
      Cu(II) site structure is almost unaffected by shortening, as is that of the Cu(I)
      center at alkaline pH in the variant with the C(112)TPH(115)PM(117) loop
      sequence. Subtle spectroscopic differences due to alterations in the spin density
      distribution at the Cu(II) site can be attributed mainly to changes in the
      hydrogen-bonding pattern. Electron transfer is almost unaffected by the
      introduction of the C(112)TPH(115)PFM(118) loop, but removal of the Phe residue
      has a sizable effect on reactivity, probably because of diminished homodimer
      formation. At mildly acidic pH values, the His-115 ligand protonates and
      dissociates from the cuprous ion, an effect that has a dramatic influence on the
      reactivity of cupredoxins. These studies demonstrate that the amicyanin loop
      adopts a conformation identical to that found in the native protein when
      introduced into azurin, that a shorter than naturally occurring C-terminal active
      site loop can support a functional T1 copper site, that CTPHPM is the minimal
      loop length required for binding this ubiquitous electron transfer center, and
      that the length and sequence of a metal-binding loop regulates a range of
      structural and functional features of the active site of a metalloprotein.

PMID- 16651528
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic
      neuronal cell death in association with IL-6.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to
      decrease ischemic neuronal damage and increase IL-6 secretion in rats. However,
      the mechanisms underlying neuroprotection are still to be fully elucidated. The
      present study was designed to investigate the role played by PACAP and IL-6 in
      mediating neuroprotection after ischemia in a null mouse. Infarct volume,
      neurological deficits, and cytochrome c in cytoplasm were higher in PACAP(+/-)
      and PACAP(-/-) mice than in PACAP(+/+) animals after focal ischemia, although the
      severity of response was ameliorated by the injection of PACAP38. A decrease in
      mitochondrial bcl-2 was also accentuated in PACAP(+/-) and PACAP(-/-) mice, but
      the decrease could be prevented by PACAP38 injection. PACAP receptor 1 (PAC1R)
      immunoreactivity was colocalized with IL-6 immunoreactivity in neurons, although
      the intensity of IL-6 immunoreactivity in PACAP(+/-) mice was less than that in
      PACAP(+/+) animals. IL-6 levels increased in response to PACAP38 injection, an
      effect that was canceled by cotreatment with the PAC1R antagonist. However,
      unlike in wild-type controls, PACAP38 treatment did not reduce the infarction in
      IL-6 null mice. To clarify the signaling pathway associated with the activity of
      PACAP and IL-6, phosphorylated STAT (signal transducer and activator of
      transcription) 3, ERK (extracellular signal-regulated kinase), and AKT levels
      were examined in PACAP(+/-) and IL-6 null mice after ischemia. Lower levels of
      pSTAT3 and pERK were observed in the PACAP(+/-) mice, whereas a reduction in
      pSTAT3 was recorded in the IL-6 null mice. These results suggest that PACAP
      prevents neuronal cell death after ischemia via a signaling mechanism involving
      IL-6.

PMID- 16651529
TI  - Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and
      embryo death in mice.
AB  - Errors in meiotic chromosome segregation are the leading cause of spontaneous
      abortions and birth defects. Almost all such aneuploidy derives from meiotic
      errors in females, with increasing maternal age representing a major risk factor.
      It was recently reported that histones are globally deacetylated in mammalian
      oocytes during meiosis but not mitosis. In the present study, inhibition of
      meiotic histone deacetylation was found to induce aneuploidy in fertilized mouse
      oocytes, which resulted in embryonic death in utero at an early stage of
      development. In addition, a histone remained acetylated in the oocytes of older
      (10-month-old) female mice, suggesting that the function for histone
      deacetylation is decreased in the oocytes of such mice. Thus, histone
      deacetylation may be involved in the fair distribution of chromosomes during
      meiotic division. The high incidence of aneuploidy in the embryos of older
      females may be due to inadequate meiotic histone deacetylation.

PMID- 16651530
TI  - Requirement of Rac1 in the development of cardiac hypertrophy.
AB  - The development of cardiac hypertrophy is mediated, in part, by increase in NADPH
      oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates
      NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in
      which "phox" is phagocyte oxidase). However, it is not known which Rac isoform
      mediates this effect in the heart. Here we show that Rac1 is critical for
      generating oxidative stress and producing cardiac hypertrophy in the adult heart.
      The Rac1 gene was temporally and specifically deleted in adult mouse
      cardiomyocytes (c-Rac1(-/-)). Compared with wild-type or Rac1 heterozygous mice,
      the hearts of c-Rac1(-/-) mice showed decreased gp91(phox) and p67(phox)
      interaction, NADPH oxidase activity, and myocardial oxidative stress in response
      to angiotensin II (400 ng/kg per day for 2 weeks) stimulation. This result
      correlated with decreased myocardial hypertrophy. These results indicate that
      Rac1 is critical for the hypertrophic response in the heart and suggest that
      therapies which target myocardial Rac1 may be beneficial in the treatment of
      cardiac hypertrophy.

PMID- 16651531
TI  - Self-recognition, color signals, and cycles of greenbeard mutualism and altruism.
AB  - Altruism presents a challenge to evolutionary theory because selection should
      favor selfish over caring strategies. Greenbeard altruism resolves this paradox
      by allowing cooperators to identify individuals carrying similar alleles
      producing a form of genic selection. In side-blotched lizards, genetically
      similar but unrelated blue male morphs settle on adjacent territories and
      cooperate. Here we show that payoffs of cooperation depend on asymmetric costs of
      orange neighbors. One blue male experiences low fitness and buffers his unrelated
      partner from aggressive orange males despite the potential benefits of defection.
      We show that recognition behavior is highly heritable in nature, and we map
      genetic factors underlying color and self-recognition behavior of genetic
      similarity in both sexes. Recognition and cooperation arise from genome-wide
      factors based on our mapping study of the location of genes responsible for self
      recognition behavior, recognition of blue color, and the color locus. Our results
      provide an example of greenbeard interactions in a vertebrate that are typified
      by cycles of greenbeard mutualism interspersed with phases of transient true
      altruism. Such cycles provide a mechanism encouraging the origin and stability of
      true altruism.

PMID- 16651532
TI  - There is no universal molecular clock for invertebrates, but rate variation does
      not scale with body size.
AB  - The existence of a universal molecular clock has been called into question by
      observations that substitution rates vary widely between lineages. However,
      increasing empirical evidence for the systematic effects of different life
      history traits on the rate of molecular evolution has raised hopes that rate
      variation may be predictable, potentially allowing the "correction" of the
      molecular clock. One such example is the body size trend observed in vertebrates;
      smaller species tend to have faster rates of molecular evolution. This effect has
      led to the proposal of general predictive models correcting for rate
      heterogeneity and has also been invoked to explain discrepancies between
      molecular and paleontological dates for explosive radiations in the fossil
      record. Yet, there have been no tests of an effect in any nonvertebrate taxa. In
      this study, we have tested the generality of the body size effect by surveying a
      wide range of invertebrate metazoan lineages. DNA sequences and body size data
      were collected from the literature for 330 species across five phyla.
      Phylogenetic comparative methods were used to investigate a relationship between
      average body size and substitution rate at both interspecies and interfamily
      comparison levels. We demonstrate significant rate variation in all phyla and
      most genes examined, implying a strict molecular clock cannot be assumed for the
      Metazoa. Furthermore, we find no evidence of any influence of body size on
      invertebrate substitution rates. We conclude that the vertebrate body size effect
      is a special case, which cannot be simply extrapolated to the rest of the animal
      kingdom.

PMID- 16651533
TI  - Stat3 activation of NF-{kappa}B p100 processing involves CBP/p300-mediated
      acetylation.
AB  - Activation of the noncanonical NF-kappaB signaling pathway involved in the
      proteolytic processing of NF-kappaB p100 to p52 is tightly regulated, and
      overproduction of p52 leads to lymphocyte hyperplasia and transformation. We have
      demonstrated that active but not latent Stat3, expressed in many types of human
      cancers involved in cell proliferation and survival, induces p100 processing to
      p52 by activation of IKKalpha and subsequent phosphorylation of p100. The Stat3
      mediated p100 processing to p52 requires activation of Stat3 by the
      acetyltransferase activity of cAMP-response element-binding protein (CREB)
      binding protein (CBP)/p300. A mutant of Stat3 defective in acetylation blocked
      Stat3-mediated p100 processing to p52 and acted as a dominant negative in
      blocking the production of p52. Furthermore, overexpression of p52 protected
      cells from apoptotic cell death. Thus, activation of the processing of p100 to
      p52 by Stat3 may represent one of the common pathways used by cancer cells to
      survive and escape therapy.

PMID- 16651534
TI  - On the Pleistocene extinctions of Alaskan mammoths and horses.
AB  - The fossil record has been used to shed light on the late Pleistocene megafaunal
      extinctions in North America and elsewhere. It is therefore important to account
      for variability due to the incompleteness of the fossil record and error in
      dating fossil remains. Here, a joint confidence region for the extinction times
      of horses and mammoths in Alaska is constructed. The results suggest that a prior
      claim that the extinction of horses preceded the arrival of humans cannot be made
      with confidence.

PMID- 16651535
TI  - Mammalian cell survival and processing in supercritical CO(2).
AB  - We demonstrate that mammalian cells can survive for 5 min within high-pressure
      CO(2)(.) Cell survival was investigated by exposing a range of mammalian cell
      types to supercritical CO(2) (scCO(2)) (35 degrees C, 74 bar; 1 bar = 100 kPa)
      for increasing exposure and depressurization times. The myoblastic C2C12 cell
      line, 3T3 fibroblasts, chondrocytes, and hepatocytes all displayed appreciable
      but varying metabolic activity with exposure times up to 1 min. With
      depressurization times of 4 min, cell population metabolic activity was >/=70% of
      the control population. Based on survival data, we developed a single-step
      scCO(2) technique for the rapid production of biodegradable poly(dl-lactic acid)
      scaffolds containing mammalian cells. By using optimum cell-survival conditions,
      scCO(2) was used to process poly(dl-lactic acid) containing a cell suspension,
      and, upon pressure release, a polymer sponge containing viable mammalian cells
      was formed. Cell functionality was demonstrated by retention of an osteogenic
      response to bone morphogenetic protein-2 in C2C12 cells. A gene microarray
      analysis showed no statistically significant changes in gene expression across
      4,418 genes by a single-class t test. A significance analysis of microarrays
      revealed only eight genes that were down-regulated based on a delta value of
      1.0125 and a false detection rate of 0.

PMID- 16651536
TI  - Progestin is an essential factor for the initiation of the meiosis in
      spermatogenetic cells of the eel.
AB  - Meiosis is an indispensable process of sexual reproduction. However, detailed
      information on the regulatory mechanisms that initiate meiosis is not available.
      Progestins are important steroids regulating final maturation in male and female
      vertebrates. In male teleosts, it is known that progestin induces spermiation and
      sperm maturation. However, a role for progestin in early spermatogenesis or
      meiosis has not yet been described. In this study, we examined the functions of
      progestin on the initiation of meiosis in male Japanese eel. A natural progestin
      in teleost fish 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) and its receptors
      were present in the testis at an early stage of spermatogenesis. By using an eel
      testicular culture system, DHP was shown to induce DNA replication in
      spermatogonia. Although 11-ketotestosterone, a known initiator of
      spermatogenesis, also stimulated DNA synthesis in spermatogonia, antibodies
      against DHP prevented DNA replication when added during the period in which
      meiosis was initiated. DHP treatment also induced the expression of meiosis
      specific markers, such as DmcI and Spo11. Furthermore, Spo11 expression and
      synaptonemal complexes, specific features of the meiotic prophase, were detected
      in testicular fragments cultured with DHP in some germ cells that showed
      morphological characteristics of undifferentiated spermatogonia. We conclude that
      DHP, a progestin, is an essential factor for the initiation of meiosis.

PMID- 16651537
TI  - Proteomic identification of oncogenic chromosomal translocation partners encoding
      chimeric anaplastic lymphoma kinase fusion proteins.
AB  - The anaplastic lymphoma kinase (ALK) on 2p23 is a tyrosine kinase that forms
      chimeric fusions with numerous translocation partners. We describe a mass
      spectrometry-based approach for the identification of ALK fusion partners. This
      approach accurately identified the nucleophosmin (NPM)-ALK fusion protein in an
      anaplastic large cell lymphoma (ALCL)-derived cell line carrying the
      t(2;5)(p23;q35), and the TPM3-ALK in a clinical biopsy of inflammatory
      myofibroblastic tumor (IMT) carrying the t(1;2)(q21;p23). This study shows the
      ability of mass spectrometry to identify oncogenic chimeric proteins resulting
      from chromosomal rearrangements. This strategy can be adapted for the
      identification of known and unknown translocation partners of chimeric ALK fusion
      proteins involved in oncogenesis.

PMID- 16651538
TI  - Construction and characterization of infectious intragenotypic and intergenotypic
      hepatitis C virus chimeras.
AB  - Chronic liver disease caused by infection with hepatitis C virus (HCV) is an
      important global health problem that currently affects 170 million people. A
      major impediment in HCV research and drug development has been the lack of
      culture systems supporting virus production. This obstacle was recently overcome
      by using JFH1-based full-length genomes that allow production of viruses
      infectious both in vitro and in vivo. Although this improvement was important,
      because of the restriction to the JFH1 isolate and a single chimera consisting of
      J6CF and JFH1-derived sequences, broadly based comparative studies between
      different HCV strains were not possible. Therefore, in this study we created a
      series of further chimeric genomes allowing production of infectious genotype
      (GT) 1a, 1b, 2a, and 3a particles. With the exception of the GT3a/JFH1 chimera,
      efficient virus production was obtained when the genome fragments were fused via
      a site located right after the first transmembrane domain of NS2. The most
      efficient construct is a GT2a/2a chimera consisting of J6CF- and JFH1-derived
      sequences connected via this junction. This hybrid, designated Jc1, yielded
      infectious titers 100- to 1,000-fold higher than the parental isolate and all
      other chimeras, suggesting that determinants within the structural proteins
      govern kinetic and efficiency of virus assembly and release. Finally, we describe
      an E1-specific antiserum capable of neutralizing infectivity of all HCV chimeras.

PMID- 16651539
TI  - Signs of change: hormone receptors that regulate plant development.
AB  - Hormonal signalling plays a pivotal role in almost every aspect of plant
      development, and of high priority has been to identify the receptors that
      perceive these hormones. In the past seven months, the receptors for the plant
      hormones auxin, gibberellins and abscisic acid have been identified. These join
      the receptors that have previously been identified for ethylene, brassinosteroids
      and cytokinins. This review therefore comes at an exciting time for plant
      developmental biology, as the new findings shed light on our current
      understanding of the structure and function of the various hormone receptors,
      their related signalling pathways and their role in regulating plant development.

PMID- 16651540
TI  - Global analysis of the transcriptional network controlling Xenopus endoderm
      formation.
AB  - A conserved molecular pathway has emerged controlling endoderm formation in
      Xenopus zebrafish and mice. Key genes in this pathway include Nodal ligands and
      transcription factors of the Mix-like paired homeodomain class, Gata4-6 zinc
      finger factors and Sox17 HMG domain proteins. Although a linear epistatic pathway
      has been proposed, the precise hierarchical relationships between these factors
      and their downstream targets are largely unresolved. Here, we have used a
      combination of microarray analysis and loss-of-function experiments to examine
      the global regulatory network controlling Xenopus endoderm formation. We
      identified over 300 transcripts enriched in the gastrula endoderm, including most
      of the known endoderm regulators and over a hundred uncharacterized genes.
      Surprisingly only 10% of the endoderm transcriptome is regulated as predicted by
      the current linear model. We find that Nodal genes, Mixer and Sox17 have both
      shared and distinct sets of downstream targets, and that a number of unexpected
      autoregulatory loops exist between Sox17 and Gata4-6, between Sox17 and
      Bix1/Bix2/Bix4, and between Sox17 and Xnr4. Furthermore, we find that Mixer does
      not function primarily via Sox17 as previously proposed. These data provides new
      insight into the complexity of endoderm formation and will serve as valuable
      resource for establishing a complete endoderm gene regulatory network.

PMID- 16651541
TI  - A threshold requirement for Gbx2 levels in hindbrain development.
AB  - Gbx2 is a homeobox gene that plays a crucial role in positioning the
      mid/hindbrain organizer (isthmus), which regulates midbrain and cerebellar
      development primarily through the secreted factor FGF8. In Gbx2 null homozygotes,
      rhombomeres (r) 1-3 fail to develop and the isthmic expression of Fgf8 is reduced
      and disorganized. These mutants fail to form a cerebellum, as it is derived from
      r1. Here, we analyze mice homozygous for a Gbx2 hypomorphic allele (Gbx2(neo)).
      Quantitative RT-PCR and RNA in situ analyses indicate that the presence of a neo
      resistance cassette impairs normal Gbx2 splicing thus reducing wild-type Gbx2
      mRNA levels to 6-10% of normal levels in all domains and stages examined. In Gbx2
      hypomorphic mutants, gene marker and neuronal patterning analyses indicate that
      reduced Gbx2 expression is sufficient to support the development of r3 but not
      r2. The posterior region of r1, from which the lateral cerebellum develops, is
      unaffected in these mutants. However, the anterior region of r1 is converted to
      an isthmus-like tissue. Hence, instead of expressing r1 markers, this region
      displays robust expression of Fgf8 and Fgf17, as well as the downstream FGF
      targets Spry1 and Spry4. Additionally, we demonstrate that the cell division
      regulator cyclin D2 is downregulated, and that cellular proliferation is reduced
      in both the normal isthmus and in the mutant anterior r1. As a result of this
      transformation, the cerebellar midline fails to form. Thus, our studies
      demonstrate different threshold requirements for the level of Gbx2 gene product
      in different regions of the hindbrain.

PMID- 16651542
TI  - Roadkill attenuates Hedgehog responses through degradation of Cubitus
      interruptus.
AB  - The final step in Hedgehog (Hh) signal transduction is post-translational
      regulation of the transcription factor, Cubitus interruptus (Ci). Ci resides in
      the cytoplasm in a latent form, where Hh regulates its processing into a
      transcriptional repressor or its nuclear access as a transcriptional activator.
      Levels of latent Ci are controlled by degradation, with different pathways
      activated in response to different levels of Hh. Here, we describe the roadkill
      (rdx) gene, which is expressed in response to Hh. The Rdx protein belongs to a
      conserved family of proteins that serve as substrate adaptors for Cullin3
      mediated ubiquitylation. Overexpression of rdx reduced Ci levels and decreased
      both transcriptional activation and repression mediated by Ci. Loss of rdx
      allowed excessive accumulation of Ci. rdx manipulation in the eye revealed a
      novel role for Hh in the organization and survival of pigment and cone cells.
      These studies identify rdx as a limiting factor in a feedback loop that
      attenuates Hh responses through reducing levels of Ci. The existence of human
      orthologs for Rdx raises the possibility that this novel feedback loop also
      modulates Hh responses in humans.

PMID- 16651543
TI  - Conserved roles for Oct4 homologues in maintaining multipotency during early
      vertebrate development.
AB  - All vertebrate embryos have multipotent cells until gastrulation but, to date,
      derivation of embryonic stem (ES) cell lines has been achieved only for mouse and
      primates. ES cells are derived from mammalian inner cell mass (ICM) tissue that
      express the Class V POU domain (PouV) protein Oct4. Loss of Oct4 in mice results
      in a failure to maintain ICM and consequently an inability to derive ES cells.
      Here, we show that Oct4 homologues also function in early amphibian development
      where they act as suppressors of commitment during germ layer specification.
      Antisense morpholino mediated PouV knockdown in Xenopus embryos resulted in
      severe posterior truncations and anterior neural defects. Gastrulation stage
      embryos showed reduced expression of genes associated with uncommitted marginal
      zone cells, while the expression of markers associated with more mature cell
      states was expanded. Importantly, we have tested PouV proteins from a number of
      vertebrate species for the ability to substitute Oct4 in mouse ES cells. PouV
      domain proteins from both Xenopus and axolotl could support murine ES cell self
      renewal but the only identified zebrafish protein in this family could not.
      Moreover, we found that PouV proteins regulated similar genes in ES cells and
      Xenopus embryos, and that PouV proteins capable of supporting ES cell self
      renewal could also rescue the Xenopus PouV knockdown phenotype. We conclude that
      the unique ability of Oct4 to maintain ES cell pluripotency is derived from an
      ancestral function of this class of proteins to maintain multipotency.

PMID- 16651545
TI  - Bainbridge sets the stage on scaling in fish swimming.

PMID- 16651546
TI  - When bad things happen to good fish: the loss of hemoglobin and myoglobin
      expression in Antarctic icefishes.
AB  - The Antarctic icefishes (Family Channichthyidae) provide excellent examples of
      unique traits that can arise in a chronically cold and isolated environment.
      Their loss of hemoglobin (Hb) expression, and in some cases, loss of myoglobin
      (Mb) expression, has taught us much about the function of these proteins.
      Although absences of the proteins are fixed traits in icefishes, the losses do
      not appear to be of adaptive value. Contrary to some suggestions, loss of Hb has
      led to higher energetic costs for circulating blood, and losses of Mb have
      reduced cardiac performance. Moreover, losses of Hb and Mb have resulted in
      extensive modifications to the cardiovascular system to ensure adequate oxygen
      delivery to working muscles. Recent studies suggest that losses of Hb and Mb, and
      their associated nitric oxide (NO)-oxygenase activities, may have accelerated the
      development and evolution of these cardiovascular modifications. The high levels
      of NO that should occur in the absence of Hb and Mb have been shown in other
      animal groups to lead to an increase in tissue vascularization, an increase in
      the lumenal diameter of blood vessels, and an increase in mitochondrial
      densities. These characteristics are all hallmark traits of Antarctic icefishes.
      Homeostatic feedback mechanisms thus may have accelerated evolution of the
      pronounced cardiovascular traits of Antarctic icefishes.

PMID- 16651547
TI  - Transcriptional regulation of neuropeptide and peptide hormone expression by the
      Drosophila dimmed and cryptocephal genes.
AB  - The regulation of neuropeptide and peptide hormone gene expression is essential
      for the development and function of neuroendocrine cells in integrated
      physiological networks. In insects, a decline in circulating ecdysteroids
      triggers the activation of a neuroendocrine system to stimulate ecdysis, the
      behaviors used to shed the old cuticle at the culmination of each molt. Here we
      show that two evolutionarily conserved transcription factor genes, the basic
      helix-loop-helix (bHLH) gene dimmed (dimm) and the basic-leucine zipper (bZIP)
      gene cryptocephal (crc), control expression of diverse neuropeptides and peptide
      hormones in Drosophila. Central nervous system expression of three neuropeptide
      genes, Dromyosuppressin, FMRFamide-related and Leucokinin, is activated by dimm.
      Expression of Ecdysis triggering hormone (ETH) in the endocrine Inka cells
      requires crc; homozygous crc mutant larvae display markedly reduced ETH levels
      and corresponding defects in ecdysis. crc activates ETH expression though a 382
      bp enhancer, which completely recapitulates the ETH expression pattern. The
      enhancer contains two evolutionarily conserved regions, and both are imperfect
      matches to recognition elements for activating transcription factor-4 (ATF-4),
      the vertebrate ortholog of the CRC protein and an important intermediate in
      cellular responses to endoplasmic reticulum stress. These regions also contain a
      putative ecdysteroid response element and a predicted binding site for the
      products of the E74 ecdysone response gene. These results suggest that
      convergence between ATF-related signaling and an important intracellular steroid
      response pathway may contribute to the neuroendocrine regulation of insect
      molting.

PMID- 16651548
TI  - Flight and echolocation behaviour of whiskered bats commuting along a hedgerow:
      range-dependent sonar signal design, Doppler tolerance and evidence for 'acoustic
      focussing'.
AB  - Echolocating bats obtain three-dimensional images of their surroundings in
      complete darkness by emitting sonar signals and evaluating returning echoes. When
      flying close to objects, bats risk collision and therefore depend on the accuracy
      of images--particularly in the perceived distance of obstacles, which is coded by
      the time delay between call and echo. Yet, during flight, such accuracy is
      perturbed first because bats call and receive echoes at different positions and
      second because echoes are modified by Doppler shifts. Certain call designs avoid
      both sources of ranging error, but only for a limited range of distances [the
      'distance of focus' (DOF)]. Here, we show that whiskered bats (Myotis mystacinus)
      using broadband echolocation calls adjust call design in a range-dependent manner
      so that nearby obstacles are localised accurately. Such behaviour is adaptive
      because it reduces collision risk. The bats also reduced call duration to some
      extent as they approached obstacles so that most returning echoes arrived after
      they finished calling. This reduction in call duration during the approach to
      obstacles was neither the only nor the main factor that influenced DOF. Indeed,
      both duration and bandwidth of calls influenced DOF independently, with lower
      bandwidths and longer durations giving greater DOF. Our findings give a new
      perspective on the adaptive significance of echolocation call design in nature
      and have implications for sonar engineering.

PMID- 16651549
TI  - Common and specific inhibitory motor neurons innervate the intersegmental muscles
      in the locust thorax.
AB  - The inhibitory innervation of the intersegmental (body wall) muscles between the
      first and the second thoracic segment of the migratory locust, Locusta
      migratoria, was investigated using neuroanatomical, immunocytochemical and
      electrophysiological techniques. Three neurons located in the prothoracic
      ganglion show GABA-like immunoreactivity and project into the intersegmental
      nerve. Two are common inhibitors. One of those innervates the oblique
      intersegmental muscle M59 and two dorsal longitudinal muscles (M81 and M82). The
      second common inhibitor also innervates M59 and the ventral longitudinal muscle
      M60. The third neuron innervates M60 exclusively and, for that reason, has to be
      regarded as the first specific inhibitor ever observed in insect neuromuscular
      assemblies. According to their innervation pattern, we term these neurons
      CI(59/60), CI(59/81/82), and SI(60). CI(59/81/82) and CI(59/60) appear to be
      segmentally homologous to CI(a) and CI(b) neurons, respectively, in the other
      body segments.

PMID- 16651550
TI  - A new set of laboratory-selected Drosophila melanogaster lines for the analysis
      of desiccation resistance: response to selection, physiology and correlated
      responses.
AB  - Artificial selection experiments provide insights into the evolutionary factors
      that can shape adaptive responses and have previously been utilized to examine
      the physiological adaptations that can improve survival to desiccation in
      Drosophila melanogaster. While such studies demonstrate that multiple resistance
      mechanisms may arise via different base populations and selection regimes, water
      retention emerges as a key mechanism for desiccation survival. Here, we present
      the physiological, correlated response and life history data for a new set of
      selection lines designed for the genetic dissection of desiccation resistance.
      After 26 generations of selection for desiccation resistance, female survival
      increased twofold. In contrast to previous studies, the altered resistance was
      associated primarily with enhanced dehydration tolerance and increased mass and
      less consistently with decreased rates of water loss. Life history tradeoffs and
      correlated selection responses were examined and overlap with previously
      published data. We crossed the resistant selected lines to desiccation-sensitive
      lines from the same control background to examine how each heterozygous resistant
      chromosome (excluding four) may improve desiccation resistance and observed that
      most of the resistance was due to genes on the third and first chromosomes,
      although interaction effects with the second chromosome were also detected.
      Results are compared to other selection responses and highlight the multiple
      evolutionary solutions that can arise when organisms are faced with a common
      selection pressure, although water loss rate remains a common mechanism in all
      studies.

PMID- 16651551
TI  - Reciprocal expression of gill Na+/K+-ATPase alpha-subunit isoforms alpha1a and
      alpha1b during seawater acclimation of three salmonid fishes that vary in their
      salinity tolerance.
AB  - The upregulation of gill Na+/K+-ATPase activity is considered critical for the
      successful acclimation of salmonid fishes to seawater. The present study examines
      the mRNA expression of two recently discovered alpha-subunit isoforms of Na+/K+
      ATPase (alpha1a and alpha1b) in gill during the seawater acclimation of three
      species of anadromous salmonids, which vary in their salinity tolerance. Levels
      of these Na+/K+-ATPase isoforms were compared with Na+/K+-ATPase activity and
      protein abundance and related to the seawater tolerance of each species. Atlantic
      salmon (Salmo salar) quickly regulated plasma Na+, Cl- and osmolality levels
      within 10 days of seawater exposure, whereas rainbow trout (Oncorhynchus mykiss)
      and Arctic char (Salvelinus alpinus) struggled to ionoregulate, and experienced
      greater perturbations in plasma ion levels for a longer period of time. In all
      three species, mRNA levels for the alpha1a isoform quickly decreased following
      seawater exposure whereas alpha1b levels increased significantly. All three
      species displayed similar increases in gill Na+/K+-ATPase activity during
      seawater acclimation, with levels rising after 10 and 30 days. Freshwater
      Atlantic salmon gill Na+/K+-ATPase activity and protein content was threefold
      higher than those of Arctic char and rainbow trout, which may explain their
      superior seawater tolerance. The role of the alpha1b isoform may be of particular
      importance during seawater acclimation of salmonid fishes. The reciprocal
      expression of Na+/K+-ATPase isoforms alpha1a and alpha1b during seawater
      acclimation suggests they may have different roles in the gills of freshwater and
      marine fishes; ion uptake in freshwater fish and ion secretion in marine fishes.

PMID- 16651552
TI  - Evolution of pharyngeal behaviors and neuronal functions in free-living soil
      nematodes.
AB  - To explore the use of Caenorhabditis elegans and related nematodes for studying
      behavioral evolution, we conducted a comparative study of pharyngeal behaviors
      and neuronal regulation in free-living soil nematodes. The pharynx is divided
      into three parts: corpus, isthmus and terminal bulb, and pharyngeal behaviors
      consist of stereotyped patterns of two motions: pumping and peristalsis. Based on
      an outgroup species, Teratocephalus lirellus, the ancestral pattern of pharyngeal
      behaviors consisted of corpus pumping, isthmus peristalsis and terminal bulb
      pumping, each occurring independently. Whereas corpus pumping remained largely
      conserved, isthmus and terminal bulb behaviors evolved extensively from the
      ancestral pattern in the four major free-living soil nematode families. In the
      Rhabditidae family, which includes Caenorhabditis elegans, the anterior isthmus
      switched from peristalsis to pumping, and anterior isthmus and terminal bulb
      pumping became coupled to corpus pumping. In the Diplogasteridae family, the
      terminal bulb switched from pumping to peristalsis, and isthmus and terminal bulb
      became coupled for peristalsis. In the Cephalobidae family, isthmus peristalsis
      and terminal bulb pumping became coupled. And in the Panagrolaimidae family, the
      posterior isthmus switched from peristalsis to pumping. Along with these
      behavioral changes, we also found differences in the neuronal regulation of
      isthmus and terminal bulb behaviors. M2, a neuron that has no detectable function
      in C. elegans, stimulated anterior isthmus peristalsis in the Panagrolaimidae.
      Further, M4 was an important excitatory neuron in each family, but its exact
      downstream function varied between stimulation of posterior isthmus peristalsis
      in the Rhabditidae, isthmus/terminal bulb peristalsis in the Diplogasteridae,
      isthmus peristalsis and terminal bulb pumping in the Cephalobidae, and posterior
      isthmus/terminal bulb pumping in the Panagrolaimidae. In the Rhabditidae family,
      although M4 normally has no effect on the terminal bulb, we found that M4 can
      stimulate the terminal bulb in C. elegans if the Ca2+-activated K+ channel SLO-1
      is inactivated. C. elegans slo-1 mutants have generally increased
      neurotransmission, and in slo-1 mutants we found novel electropharyngeogram
      signals and increased pumping rates that suggested activation of M4-terminal bulb
      synapses. Thus, we suggest that the lack of M4-terminal bulb stimulations in C.
      elegans and the Rhabditidae family evolved by changes in synaptic transmission.
      Altogether, we found behavioral and neuronal differences in the isthmus and
      terminal bulb of free-living soil nematodes, and we examined potential underlying
      mechanisms of one aspect of M4 evolution. Our results suggest the utility of
      Caenorhabditis elegans and related nematodes for studying behavioral evolution.

PMID- 16651553
TI  - Removal of the chorion before hatching results in increased movement and
      accelerated growth in rainbow trout (Oncorhynchus mykiss) embryos.
AB  - We investigated the effects of the chorion on movement and growth in rainbow
      trout (Oncorhynchus mykiss) embryos. To test if the chorion restricts movement
      and growth before hatching, we manually removed the chorion 3-6 days before the
      natural time of hatching (dechorionated) and compared movement, growth and oxygen
      consumption in dechorionated embryos and in embryos whose chorions remained
      intact until the time of hatching (chorionated). Dechorionated embryos exhibited
      36 times more movement before hatching compared with intact embryos. By 10 h post
      hatch there was no difference in the number of movements between the two groups.
      At the time of hatching [30 days post-fertilization (d.p.f.)], dechorionated
      embryos had a significantly greater embryonic body dry mass compared with
      chorionated embryos, which persisted up to 45 d.p.f. At first feeding (50 d.p.f.)
      there was no significant difference in embryonic body dry mass between the two
      groups. Dechorionated embryos had a significantly greater embryonic body protein
      content after hatching (32, 33 d.p.f.) compared with chorionated embryos. Despite
      the differences in movement and growth, there were no significant differences in
      oxygen consumption between chorionated and dechorionated embryos. Furthermore,
      there was no correlation between the number of movements and oxygen consumption
      in rainbow trout embryos (chorionated, dechorionated, and hatched). Taken
      together, the data indicate that rainbow trout embryos have the capacity to be
      relatively active before hatching, but that the chorion restricts or inhibits
      movement. Moreover, precocious activity in pre-hatch embryos is correlated with
      accelerated growth and higher protein content, suggesting that the exercise
      training effect observed in adult salmonids is also present in early
      developmental stages.

PMID- 16651554
TI  - Water dynamics in the digestive tract of the freshwater rainbow trout during the
      processing of a single meal.
AB  - The temporal effects of feeding and digestion on chyme composition, specifically
      water and solid content, and net fluxes across the gastrointestinal tract, as
      well as plasma parameters, were examined in freshwater rainbow trout. A single
      meal of commercial dry pellets, incorporating ballotini beads as inert reference
      markers, was employed. Plasma Na+ levels increased by 15-20% at 2 h post-feeding,
      where Cl- levels did not change. Plasma osmolality was well regulated despite an
      initial chyme osmolality (775 mOsm) 2.8-fold higher than that in the blood
      plasma. Chyme osmolality throughout the gastrointestinal tract remained
      significantly higher than plasma osmolality for the duration of the 72 h period.
      Solid material was absorbed along the entire intestinal tract, although not in
      the stomach, necessitating the incorporation of an inert marker. A similar
      temporal pattern of transit between the ballotini beads (solid phase marker) and
      3[H]-PEG 4000 (fluid phase marker), provided support for the use of ballotini
      beads. Large additions of water to the chyme were seen in the stomach, the
      largest occurring within 2 h following feeding (7.1+/-1.4 ml kg(-1)), and
      amounted to approximately 16 ml kg(-1) over the first 12 h. As the chyme entered
      the anterior intestine, a further large water secretion (3.5+/-0.5 ml kg(-1)) was
      seen. Thereafter the water fluxes into the chyme of the anterior intestine
      decreased steadily over time, but remained positive, whereas the mid-intestine
      exhibited net absorption of water at all time points, and the posterior intestine
      demonstrated little water handling at any time. The endogenous water that was
      secreted into the anterior intestine was absorbed along the tract, which showed a
      net water flux close to zero. However, assuming that the water secreted into the
      stomach was endogenous in nature, the processing of a single meal resulted in net
      loss of endogenous water (0.24 ml kg(-1) h(-1)) to the environment, a beneficial
      consequence of the osmotic challenge offered by the food for a freshwater
      hyperosmotic regulator.

PMID- 16651555
TI  - The hydrodynamic effects of shape and size change during reconfiguration of a
      flexible macroalga.
AB  - Rocky intertidal organisms experience large hydrodynamic forces due to high water
      velocities created by breaking waves. Flexible organisms, like macroalgae, often
      experience lower drag than rigid organisms because their shape and size change as
      velocity increases. This phenomenon, known as reconfiguration, has been
      previously quantified as Vogel's E, a measure of the relationship between
      velocity and drag. While this method is very useful for comparing reconfiguration
      among organisms it does not address the mechanisms of reconfiguration, and its
      application to predicting drag is problematic. The purpose of this study was
      twofold: (1) to examine the mechanisms of reconfiguration by quantifying the
      change in shape and size of a macroalga in flow and (2) to build a mechanistic
      model of drag for reconfiguring organisms. Drag, frontal area and shape of the
      intertidal alga Chondrus crispus were measured simultaneously in a recirculating
      flume at water velocities from 0 to approximately 2 m s(-1). Reconfiguration was
      due to two separate mechanisms: whole-alga realignment (deflection of the stipe)
      at low velocities (<0.2 m s(-1)) and compaction of the crown (reduction in
      frontal area and change in shape) at higher velocities. Change in frontal area
      contributed more to drag reduction than change in drag coefficient. Drag
      coefficient and frontal area both decrease exponentially with increasing water
      velocity, and a mechanistic model of drag was developed with explicit functions
      to describe these changes. The model not only provides mechanistic parameters
      with which to compare reconfiguration among individuals and species, but also
      allows for more reliable predictions of drag at high, ecologically relevant water
      velocities.

PMID- 16651556
TI  - Partial coherence and other optical delicacies of lepidopteran superposition
      eyes.
AB  - Superposition eyes are generally thought to function ideally when the eye is
      spherical and with rhabdom tips in the focal plane of the imaging optics of facet
      lenses and crystalline cones. Anatomical data as well as direct optical
      measurements demonstrate that the superposition eyes of moths and skippers often
      deviate severely from the expected ideal case. Part of the deviation has been
      attributed to diffraction at the single facet lens, which was taken to be an
      essential limit to spatial resolution, because light traveling through different
      facet lenses was assumed to be incoherent. By considering the two-dimensional
      facet lens lattice, it is here demonstrated that many facets within a
      superposition aperture transmit coherent light, allowing a much sharper image
      than possible with single facet lens diffraction. Partial coherence therefore is
      an important aspect of superposition imaging. It is argued that broadening of the
      photoreceptor acceptance angles occurs because of optical errors in the facet
      lens-crystalline cone system other than diffraction. The transmittance of the
      superposition aperture of moths and skippers is improved by the corneal nipple
      arrays of the facet lenses, but quantitative assessment shows that the effect is
      minor.

PMID- 16651558
TI  - Characterization of a branchial epithelial calcium channel (ECaC) in freshwater
      rainbow trout (Oncorhynchus mykiss).
AB  - The entry of calcium (Ca2+) through an apical membrane epithelial calcium channel
      (ECaC) is thought to a key step in piscine branchial Ca2+ uptake. In mammals,
      ECaC is a member of the transient receptor potential (TRP) gene family of which
      two sub-families have been identified, TRPV5 and TPRV6. In the present study we
      have identified a single rainbow trout (Oncorhynchus mykiss) ECaC (rtECaC) that
      is similar to the mammalian TRPV5 and TRPV6. Phylogenetic analysis of the protein
      sequence suggests that an ancestral form of the mammalian genes diverged from
      those in the lower vertebrates prior to the gene duplication event that gave rise
      to TRPV5 and TRPV6. The putative model for Ca2+ uptake in fish proposes that the
      mitochondria-rich cell (also termed ionocyte or chloride cell) is the predominant
      or exclusive site of transcellular Ca2+ movements owing to preferential
      localisation of ECaC to the apical membrane of these cells. However, the results
      of real-time PCR performed on enriched gill cell populations as well as
      immunocytochemistry and in situ hybridisation analysis of enriched cells, cell
      cultures and whole gill sections strongly suggest that ECaC is not exclusive to
      mitochondria-rich cells but that it is also found in pavement cells. Not only was
      ECaC protein localized to areas of the gill normally having few mitochondria-rich
      cells, but there was also no consistent co-localization of ECaC- and Na+/K+
      ATPase-positive (a marker of mitochondria rich cells) cells. Taken together, the
      results of the present study suggest that although ECaC (mRNA and protein) does
      exist in trout gill, its cellular distribution is more extensive than previously
      thought, thus suggesting that Ca2+ uptake may not be restricted to mitochondria
      rich cells as was proposed in previous models.

PMID- 16651557
TI  - Vomeronasal sensory neurons from Sternotherus odoratus (stinkpot/musk turtle)
      respond to chemosignals via the phospholipase C system.
AB  - The mammalian signal transduction apparatus utilized by vomeronasal sensory
      neurons (VSNs) in the vomeronasal organ (VNO) has been richly explored, while
      that of reptiles, and in particular, the stinkpot or musk turtle Sternotherus
      odoratus, is less understood. Given that the turtle's well-known reproductive and
      mating behaviors are governed by chemical communication, 247 patch-clamp
      recordings were made from male and female S. odoratus VSNs to study the
      chemosignal-activated properties as well as the second-messenger system
      underlying the receptor potential. Of the total neurons tested, 88 (35%) were
      responsive to at least one of five complex natural chemicals, some of which
      demonstrated a degree of sexual dimorphism in response selectivity. Most notably,
      male VSNs responded to male urine with solely outward currents. Ruthenium Red, an
      IP3 receptor (IP3R) antagonist, failed to block chemosignal-activated currents,
      while the phospholipase C (PLC) inhibitor, U73122, abolished the chemosignal
      activated current within 2 min, implicating the PLC system in the generation of a
      receptor potential in the VNO of musk turtles. Dialysis of several second
      messengers or their analogues failed to elicit currents in the whole-cell patch
      clamp configuration, negating a direct gating of the transduction channel by
      cyclic adenosine monophosphate (cAMP), inositol 1,4,5-trisphosphate (IP3),
      arachidonic acid (AA), or diacylglycerol (DAG). Reversal potential analysis of
      chemosignal-evoked currents demonstrated that inward currents reversed at -5.7+/
      7.8 mV (mean +/- s.e.m.; N=10), while outward currents reversed at -28.2+/-2.4 mV
      (N=30). Measurements of conductance changes associated with outward currents
      indicated that the outward current represents a reduction of a steady state
      inward current by the closure of an ion channel when the VSN is exposed to a
      chemical stimulus such as male urine. Chemosignal-activated currents were
      significantly reduced when a peptide mimicking a domain on canonical transient
      receptor potential 2 (TRPC2), to which type 3 IP3 receptor (IP3R3) binds, was
      included in the recording pipette. Collectively these data suggest that there are
      multiple transduction cascades operational in the VSNs of S. odoratus, one of
      which may be mediated by a non-selective cation conductance that is not gated by
      IP3 but may be modulated by the interaction of its receptor with the TRPC2
      channel.

PMID- 16651559
TI  - Color discrimination in the red range with only one long-wavelength sensitive
      opsin.
AB  - The basic precondition for color vision is the presence of at least two receptor
      types with different spectral sensitivities. The sensitivity of a receptor is
      mostly defined by the opsin-based visual pigment expressed in it. We show here,
      through behavioral experiments, that the nymphalid butterfly Heliconius erato,
      although it expresses short and medium wavelength opsins and only one long
      wavelength opsin, discriminates colors in the long-wavelength range (590 nm, 620
      nm and 640 nm), whereas another nymphalid, Vanessa atalanta, despite having color
      vision, is unable to do so. In the eyes of H. erato we identified filtering
      pigments very close to the rhabdom which differ between ommatidia and produce the
      yellow and red ommatidial reflection seen under orthodromic illumination. The
      eyes of V. atalanta lack the filtering pigments, and reflect a homogeneous
      orange. We hypothesize that the filtering pigments found in the eyes of H. erato
      may shift the spectral sensitivity peak of the long wavelength receptors in some
      ommatidia towards longer wavelengths. The comparison of the signals between the
      two new receptor types makes color discrimination in the red range possible. To
      our knowledge, this is the first behavioral proof of color vision based on
      receptors expressing the same opsin.

PMID- 16651560
TI  - The role of the sarcoplasmic reticulum in the generation of high heart rates and
      blood pressures in reptiles.
AB  - The functional significance of the sarcoplasmic reticulum (SR) in the generation
      of high heart rates and blood pressures was investigated in four species of
      reptile; the turtle, Trachemys scripta; the python, Python regius, the tegu
      lizard, Tupinanvis merianae, and the varanid lizard, Varanus exanthematicus.
      Force-frequency trials and imposed pauses were performed on ventricular and
      atrial tissue from each species with and without the SR inhibitor ryanodine, and
      in the absence and presence of adrenaline. In all species, an imposed pause of 1
      or 5 min caused a post-rest decay of force, and a negative force-frequency
      response was observed in all species within their in vivo frequency range of
      heart rates. These relationships were not affected by either ryanodine or
      adrenaline. In ventricular strips from varanid lizards and pythons, ryanodine
      caused significant reductions in twitch force within their physiologically
      relevant frequency range. In atrial tissue from the tegu and varanid lizards, SR
      inhibition reduced twitch force across the whole of their physiological frequency
      range. In contrast, in the more sedentary species, the turtle and the python, SR
      inhibition only decreased twitch force at stimulation frequencies above maximal
      in vivo heart rates. Adrenaline caused an increase in twitch force in all species
      studied. In ventricular tissue, this positive inotropic effect was sufficient to
      overcome the negative effects of ryanodine. In atrial tissue however, adrenaline
      could only ameliorate the negative effects of ryanodine at the lower pacing
      frequencies. Our results indicate that reptiles recruit Ca2+ from the SR for
      force development in a frequency and tissue dependent manner. This is discussed
      in the context of the development of high reptilian heart rates and blood
      pressures.

PMID- 16651561
TI  - Electrochemical gradients for Na+, K+, Cl- and H+ across the apical membrane in
      Malpighian (renal) tubule cells of Rhodnius prolixus.
AB  - Measurements of intracellular and luminal ion activities as well as membrane
      potential were used to calculate electrochemical gradients for Cl-, Na+, K+ and
      H+ across the apical membrane during fluid secretion by Malpighian tubules of
      Rhodnius prolixus. The results show that the contribution of Na+/H+ and/or K+/H+
      exchangers to fluid secretion is feasible both in unstimulated and serotonin
      stimulated tubules. Similarly, the electrochemical potential for Cl- is
      consistent with the passive movement of Cl- from cell to lumen through Cl-
      channels. The contribution of apical K+:Cl- cotransport and/or paracellular Cl-
      movement to net transepithelial ion transport is thermodynamically unfeasible. pH
      in the lumen (pH 6.08+/-0.1, N=6) was more acid than in the bath (pH 7.25+/-0.01,
      N=26) and serotonin stimulation produced a significant increase in lumen pH to
      6.32+/-0.04 (N=5). Intracellular pH was 6.97+/-0.01 and 6.82+/-0.04 in
      unstimulated and serotonin-stimulated tubules, respectively. Lumen pH was altered
      whereas intracellular pH was tightly regulated during serotonin and bumetanide
      treatment. Furthermore, DIDS or amiloride treatment did not affect intracellular
      pH. However, intracellular pH shifted 0.25 pH units more acid in Na+-free saline,
      suggesting that a Na+-dependent pH regulatory mechanism is at play in steady
      state pH regulation during fluid secretion by Malpighian tubules of Rhodnius
      prolixus. The data are consistent with a role for a basolateral Na+/H+ exchanger
      in intracellular pH regulation during fluid secretion.

PMID- 16651562
TI  - The effects of temperature on peripheral neuronal function in eurythermal and
      stenothermal crustaceans.
AB  - To determine whether neuronal function in Antarctic crustaceans is adapted to the
      low and narrow range of temperatures at which these animals live, we have
      compared conduction velocities in the peripheral nervous systems of two temperate
      species, the decapod Carcinus maenas and the isopod Ligia oceanica, and two
      Antarctic species, the isopod Glyptonotus antarcticus and the amphipod
      Paraceradocus gibber. Neuronal conduction velocity differs among the species in
      the order C. maenas > G. antarcticus > P. gibber > L. oceanica. When measured at
      the normal environmental temperatures characteristic of each species, conduction
      velocity of the Antarctic peracarid P. gibber is greater than that of its similar
      sized temperate relative L. oceanica, demonstrating complete thermal
      compensation. The temperate decapod C. maenas has a higher thermal dependence of
      neuronal conduction velocity than either of the Antarctic species, G. antarcticus
      and P. gibber, but the temperate L. oceanica does not. These data, when collated
      with published values, indicate that peracarid crustaceans (L. oceanica, G.
      antarcticus and P. gibber) have lower neuronal conduction velocities and a lower
      thermal dependence of neuronal conduction velocity than do other arthropods,
      irrespective of habitat. There is a linear dependence of conduction velocity on
      temperature down to -1.8 degrees C in all three species. Our data extend by more
      than 10 degrees the lower range of temperatures at which conduction velocities
      have been tested systematically in previous studies. The upper thermal block of
      neuronal conduction is similar in C. maenas, G. antarcticus, P. gibber and L.
      oceanica at 24.5, 19.5, 21.5 and 19.5 degrees C, respectively. This suggests that
      failure to conduct action potentials is not what determines the mortality of
      Antarctic invertebrates at approximately 10 degrees C. The excitability of axons
      in the leg nerve of G. antarcticus is not affected by temperatures ranging from 
      1.8 to +18 degrees C. The responses of sensory neurones activated by movements of
      spines on the leg, however, are strongly modulated by temperature, with maximal
      responses at 5-10 degrees C; well above the normal environmental temperature
      range for the species. The responses fail at 20-22 degrees C. The number of large
      diameter axons (which produce the fast action potentials recorded in this study)
      is the same in L. oceanica and G. antarcticus, but the median axon diameter is
      greater in L. oceanica than G. antarcticus. In G. antarcticus, however, there are
      glial wrappings around some large (>5 microm diameter) axons that may increase
      their conduction velocity. Such wrappings are not found in L. oceanica.

PMID- 16651563
TI  - Immunolocalisation of the D. melanogaster Nramp homologue Malvolio to gut and
      Malpighian tubules provides evidence that Malvolio and Nramp2 are orthologous.
AB  - Nramp (Slc11a1) genes in mammals are associated with the transport of iron and
      other divalent cations; Nramp1 in macrophages involved in the innate immune
      response against intracellular pathogens, and Nramp2 with duodenal iron uptake
      and the transferrin-transferrin-receptor pathway of iron assimilation. The
      Drosophila melanogaster Nramp-related gene is known as Malvolio. The localisation
      of Malvolio protein was inferred from the enhancer trap line initially used to
      isolate Malvolio in a screen for mutants with defects in taste perception. Here
      we describe the generation of a Malvolio-reactive polyclonal antibody and apply
      it to evaluate Malvolio localisation during stages of D. melanogaster
      development, and compare the results with the localisation of the enhancer trap
      line identified with beta-galactosidase. All immunolocalisation studies have been
      confirmed to be specific with Malvolio-blocking peptides. Our results
      demonstrated expression within Malpighian tubules, testis, brain, the amnioserosa
      of embryos, the larval and adult alimentary canal. Expression within the gut was
      of significant interest, as mammalian Nramp2 in the gut plays a primary role in
      the acquisition of dietary iron. We confirm expression within the central nervous
      system and in cells of the haematopoietic system. By immunohistochemistry we
      showed that expression within cells was either punctuate, diffuse cytoplasmic or
      plasma membrane associated, or both. The staining within the gut indicates a
      degree of conservation of components for iron acquisition between flies and
      mammals, suggesting that a comparable mechanism has been retained during
      evolution.

PMID- 16651564
TI  - Seasonal variation in mussel byssal thread mechanics.
AB  - The blue mussel, Mytilus edulis, attaches itself to the substrate by producing a
      radially arranged complex of collagenous byssal threads. The strength of byssal
      attachment, or tenacity, has been shown to vary seasonally on Rhode Island
      shores, increasing twofold in spring in comparison with fall. It was previously
      assumed that this seasonality was due to increased thread production following
      periods of increased wave action; however, recent findings do not support this
      view. As an alternate hypothesis, this study evaluates the contribution of
      seasonal changes in the material properties of byssal threads to an annual cycle
      in mussel attachment strength. Tensile mechanical tests were performed
      seasonally, on both newly produced threads and on threads outplanted in the field
      for up to nine weeks. Threads produced in spring were over 60% stronger and 83%
      more extensible than threads produced in all other seasons. The mechanical
      integrity of byssal threads also deteriorated over time in spring and summer.
      These results suggest that reduced attachment strength in fall reflects the
      production of inferior quality threads following a period of increased decay.
      Here, we propose a new scheme where variation in byssal thread material
      properties, rather than quantity, explains the seasonal pattern in attachment
      strength observed on Rhode Island shores.

PMID- 16651565
TI  - Treatment of femoro-acetabular impingement: preliminary results of labral
      refixation.
AB  - BACKGROUND: Recent advances in the understanding of the anatomy and function of
      the acetabular labrum suggest that it is important for normal joint function. We
      found no available data regarding whether labral refixation after treatment of
      femoro-acetabular impingement affects the clinical and radiographic results.
      METHODS: We retrospectively reviewed the clinical and radiographic results of
      fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent
      arthrotomy and surgical dislocation of the hip to allow trimming of the
      acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the
      torn labrum was resected (Group 1); in the next thirty-five hips, the intact
      portion of the labrum was reattached to the acetabular rim (Group 2). At one and
      two years postoperatively, the Merle d'Aubigne clinical score and the Tonnis
      arthrosis classification system were used to compare the two groups. RESULTS: At
      one year postoperatively, both groups showed a significant improvement in their
      clinical scores (mainly pain reduction) compared with their preoperative values
      (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years
      postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent
      result, 48% had a good result, 20% had a moderate result, and 4% had a poor
      result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an
      excellent result, 14% had a good result, and 6% had a moderate result. Comparison
      of the clinical scores between the two groups revealed significantly better
      outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01).
      Radiographic signs of osteoarthritis were significantly more prevalent in Group 1
      than in Group 2 at one year (p = 0.02) and at two years (p = 0.009). CONCLUSIONS:
      Patients treated with labral refixation recovered earlier and had superior
      clinical and radiographic results when compared with patients who had undergone
      resection of a torn labrum. Although the results must be considered preliminary,
      we now recommend refixation of the intact portion of the labrum after trimming of
      the acetabular rim during surgical treatment of femoro-acetabular impingement.

PMID- 16651566
TI  - Arthroscopic debridement for osteoarthritis of the knee.
AB  - BACKGROUND: The role of arthroscopic debridement in the treatment of
      osteoarthritis of the knee remains to be defined, and few clinical and
      radiographic characteristics have been quantitatively associated with the
      outcome. The hypothesis of this study was that the outcome of arthroscopic
      debridement for osteoarthritis of the knee is associated with preoperative
      clinical and radiographic features and intraoperative characteristics and that
      there are subsets of patients who are more and less likely to respond favorably
      to the treatment. METHODS: We performed a cross-sectional study of a consecutive
      cohort of 122 patients who underwent arthroscopic debridement for the treatment
      of osteoarthritis of the knee that had been unresponsive to anti-inflammatory
      therapy. One hundred and ten patients were followed for a mean of thirty-four
      months. Pain was assessed with the pain domain of the Knee Society scoring
      system. Radiographs were scored with the Kellgren-Lawrence method, and limb
      alignment and the widths of the medial and lateral joint spaces were measured.
      The severity of cartilage lesions was scored intraoperatively with a modified
      Noyes grading system. Specific methods of data collection and analysis were
      incorporated to minimize bias. RESULTS: Fifty-two (90%) of fifty-eight knees with
      mild arthritis, normal alignment, and a joint space width of > or = 3 mm were
      improved after arthroscopic debridement. Conversely, only five (25%) of twenty
      knees with severe arthritis, limb malalignment, and a joint space width of < 2 mm
      had substantial relief of symptoms. Of seventy-two patients who had improvement,
      forty-four (61%) had it within six months after the arthroscopy. The severity of
      the lesion was highly predictive of the clinical outcome both in patients with
      mild arthritis and in those with severe arthritis. CONCLUSIONS: The severity of
      the arthritis, as assessed preoperatively with radiography and intraoperatively
      by rating the severity of cartilage lesions, influences the clinical outcome of
      arthroscopic debridement of an osteoarthritic knee. Knees with severe arthritis
      fare poorly, whereas those with mild arthritis fare well. We could not predict
      the outcome for knees with moderate arthritis. We believe that these observations
      are relevant for establishing indications for arthroscopy in patients with
      osteoarthritis of the knee and may be useful for designing studies with a more
      rigorous experimental design.

PMID- 16651567
TI  - A sixteen-year follow-up of three operative techniques for the treatment of acute
      ruptures of the anterior cruciate ligament.
AB  - BACKGROUND: This study compares three surgical procedures that we used in the
      past to treat ruptures of the anterior cruciate ligament: acute primary repair,
      acute repair augmented with a synthetic ligament-augmentation device, and acute
      repair augmented with autologous bone-patellar tendon-bone graft. METHODS: This
      is the third report on a group of patients who were randomized to the three
      different procedures between 1986 and 1988. There were fifty patients in each
      group. The patients were evaluated prospectively at one, two, five, and sixteen
      years with use of the Tegner activity score and the Lysholm functional score.
      Stability of the knee was assessed with clinical examination and with use of the
      KT-1000 arthrometer. RESULTS: One hundred and twenty-nine (88%) of the 147
      patients who were available for follow-up completed the study. Eleven patients
      (24%) who had a primary repair, four patients (10%) who had repair with a
      ligament augmentation device, and one patient (2%) who had augmentation with
      autologous bone-patellar tendon-bone graft underwent anterior cruciate ligament
      revisions between the primary operation and the sixteen-year follow-up
      examination. The rate of revision was ten times higher in the group that had
      primary repair than in the group that had repair with bone-patellar tendon-bone
      graft (p = 0.003). In the remaining patients, those who had repair with a bone
      patellar tendon-bone graft had significantly more stable knees than those who had
      repair with a ligament augmentation device, as measured by the Lachman test (p =
      0.026). Nine (11%) of the eighty-five patients for whom data were available had
      osteoarthritis in the primarily reconstructed knee, and three patients (3.5%) had
      osteoarthritis in the contralateral knee at sixteen years (p = 0.001); no
      difference was noted among the three groups. The mean Lysholm score at sixteen
      years was 88 points for the knees that had primary repair, 85 points for those
      that had repair with the ligament augmentation device, and 90 points for those
      managed with a bone-patellar tendon-bone graft (p = 0.286). CONCLUSIONS: At long
      term (sixteen-year) follow-up, the rate of revision anterior cruciate ligament
      surgery is much higher following primary repair than after primary repair
      augmented by a bone-patellar tendon-bone graft. It can be expected that
      approximately 10% of patients undergoing anterior cruciate ligament
      reconstruction acutely will have osteoarthritis develop in the reconstructed
      knee. We no longer perform any of these surgical techniques as open procedures.

PMID- 16651568
TI  - Proximal femoral allograft treatment of Vancouver type-B3 periprosthetic femoral
      fractures after total hip arthroplasty.
AB  - BACKGROUND: Periprosthetic femoral fractures following total hip arthroplasty are
      becoming more prevalent. When a fracture occurs in a femur with substantial
      proximal bone deficiency, the surgical options for revision are limited. One
      option includes the use of a proximal femoral allograft. METHODS: We
      retrospectively assessed the results and complications of the use of a proximal
      femoral allograft to treat twenty-five Vancouver type-B3 periprosthetic fractures
      in twenty-four patients. The mean duration of follow-up was 5.1 years. Clinical
      results were graded with use of the Harris hip score. Radiographs were assessed
      for evidence of trochanteric union, host-allograft union, allograft resorption,
      and component loosening or fracture. Failure of the procedure was defined as the
      need for revision surgery requiring graft removal. RESULTS: The mean
      postoperative Harris hip score was 70.8. At the time of the final follow-up,
      twenty-one of the twenty-four patients reported no or mild pain and twenty-three
      patients were able to walk; fifteen required a walking aid. The greater
      trochanter united in seventeen of the twenty-five hips, and osseous union of the
      allograft to the host femur occurred in twenty hips. There was mild graft
      resorption in four hips and moderate graft resorption in two. Four (16%) of the
      twenty-five hips required repeat revision. CONCLUSIONS: The use of a proximal
      femoral allograft for the treatment of a Vancouver type-B3 periprosthetic femoral
      fracture can provide a satisfactory result in terms of pain relief and function
      at five years.

PMID- 16651569
TI  - Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A
      randomized trial.
AB  - BACKGROUND: Postoperative analgesia with the use of parenteral opioids or
      epidural analgesia can be associated with troublesome side effects. Good
      perioperative analgesia facilitates rehabilitation, improves patient
      satisfaction, and may reduce the hospital stay. We investigated the analgesic
      effect of locally injected drugs around a total knee prosthesis. METHODS: Sixty
      four patients undergoing total knee arthroplasty were randomized either to
      receive a periarticular intraoperative injection containing ropivacaine,
      ketorolac, epimorphine, and epinephrine or to receive no injection. The
      perioperative analgesic regimen was standardized. All patients in both groups
      received patient-controlled analgesia for twenty-four hours after the surgery,
      and this was followed by standard analgesia. Visual analog scores for pain,
      during activity and at rest, and for patient satisfaction were recorded
      preoperatively and postoperatively and at the six-week follow-up examination. The
      consumption of patient-controlled analgesia at specific postoperative time-points
      and the overall analgesic requirement were measured. RESULTS: The patients who
      had received the injection used significantly less patient-controlled analgesia
      at six hours, at twelve hours, and over the first twenty-four hours after the
      surgery. In addition, they had higher visual analog scores for patient
      satisfaction and lower visual analog scores for pain during activity in the post
      anesthetic-care unit and four hours after the operation. No cardiac or central
      nervous system toxicity was observed. CONCLUSIONS: Intraoperative periarticular
      injection with multimodal drugs can significantly reduce the requirements for
      patient-controlled analgesia and improve patient satisfaction, with no apparent
      risks, following total knee arthroplasty.

PMID- 16651570
TI  - Treatment of glenohumeral arthritis with a hemiarthroplasty: a minimum five-year
      follow-up outcome study.
AB  - BACKGROUND: Glenohumeral hemiarthroplasty is well established as a method to
      treat glenohumeral arthritis. This study was designed to report longer-term
      results and to provide a decision model to assist surgeons in achieving
      successful outcomes. Our selection strategy for hemiarthroplasty included
      shoulders with (1) a concentric glenoid with eburnated bone, (2) a nonconcentric
      glenoid that could be converted to a smooth concentric surface, and (3) a humeral
      head centered within the glenoid after soft-tissue balancing. METHODS: Fifty
      seven consecutive patients (sixty-four shoulders) who had osteoarthritis of the
      glenohumeral joint, without advanced disease in the glenoid, were treated with
      hemiarthroplasty. In each instance, a modular prosthesis was implanted. Clinical
      assessment was performed preoperatively and at one-year intervals postoperatively
      for at least five years with use of patient self-assessment instruments,
      including the American Shoulder and Elbow Surgeons questionnaire, the Simple
      Shoulder Test, and a visual analog pain scale. A detailed radiographic analysis
      was performed to determine the presence of glenohumeral subluxation,
      periprosthetic radiolucency, and glenoid bone loss. RESULTS: Forty-three patients
      (fifty shoulders) were followed for a minimum of five years (mean, 7.5 years). Of
      the remaining fourteen patients (fourteen shoulders), ten were lost to follow-up,
      three had died, and one was excluded. For the Simple Shoulder Test, and for every
      visual analog scale measure, the results at the final follow-up evaluation were
      significantly better than the preoperative results (p < 0.0001 for each). The
      mean Simple Shoulder Test score at the time of the final follow-up was 9.4
      positive responses compared with 9.7 positive responses at the two-year
      evaluation (p = 0.32), and the mean visual analog scale score for pain was 18.6
      points compared with 14.9 points at two years (p = 0.45). Radiographic analysis
      showed the majority of stems had either no lucency or lucencies only near the tip
      of the stem. Glenoid bone loss and subluxation improved postoperatively, and the
      results were maintained at the final follow-up evaluation. CONCLUSIONS: Shoulder
      hemiarthroplasty provides sustained good-to-excellent pain relief and functional
      improvement at five to ten years postoperatively in carefully selected patients
      with osteoarthritis.

PMID- 16651571
TI  - Predictors of short-term functional outcome following ankle fracture surgery.
AB  - BACKGROUND: Ankle fractures are among the most common injuries treated by
      orthopaedic surgeons. However, very few investigators have examined the
      functional recovery following ankle fracture surgery and, to our knowledge, none
      have analyzed factors that may predict functional recovery. In this study, we
      evaluated predictors of short-term functional outcome following surgical
      stabilization of ankle fractures. METHODS: Over three years, 232 patients who
      sustained a fracture of the ankle and were treated surgically were followed
      prospectively, for a minimum of one year. Trained interviewers recorded baseline
      characteristics, including patient demographics, medical comorbidities, and
      functional status according to the Short Musculoskeletal Function Assessment
      (SMFA). Laboratory findings, the American Society of Anesthesiologists (ASA)
      class, and operative findings were recorded from the chart during
      hospitalization. Follow-up information included the occurrence of complications
      or additional surgery, weight-bearing status, functional status according to the
      SMFA, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot
      score. The data were analyzed to determine predictors of functional recovery at
      three months, six months, and one year postoperatively. RESULTS: Complete follow
      up data were available for 198 patients (85%). At one year, 174 (88%) of the
      patients had either no or mild ankle pain and 178 (90%) had either no limitations
      or limitations only in recreational activities. According to the AOFAS ankle
      hindfoot score, 178 (90%) of the patients had > or = 90% functional recovery. A
      patient age of less than forty years was a predictor of recovery, as measured
      with the SMFA subscores, at six months after the ankle fracture. At one year,
      however, age was no longer a predictor of recovery. Patients who were younger
      than forty were more likely to recover > or = 90% of function (p = 0.004), and
      men were more likely than women to recover function (p = 0.02). ASA Class 1 or 2
      (p = 0.03) and an absence of diabetes (p = 0.02) were also predictors of better
      functional recovery at one year. SMFA subscores were below average at baseline,
      indicating a healthy population. At three and six months postoperatively, all
      SMFA subscores were significantly higher than the baseline subscores (p < 0.001);
      however, at one year, the SMFA subscores were almost back to the baseline, normal
      level. CONCLUSIONS: One year after ankle fracture surgery, patients are generally
      doing well, with most experiencing little or mild pain and few restrictions in
      functional activities. They have a significant improvement in function compared
      with six months after the surgery. Younger age, male sex, absence of diabetes,
      and a lower ASA class are predictive of functional recovery at one year following
      ankle fracture surgery. It is important to counsel patients and their families
      regarding the expected functional recovery after an ankle injury.

PMID- 16651572
TI  - Treatment of multidirectionally unstable supracondylar humeral fractures in
      children. A modified Gartland type-IV fracture.
AB  - BACKGROUND: There is an uncommon subset of supracondylar humeral fractures in
      children that are so unstable they can displace into both flexion and extension.
      The purposes of this study were to describe this subset of supracondylar
      fractures and to report a new technique of closed reduction and percutaneous
      pinning for their treatment. METHODS: In a retrospective review of 297
      consecutive displaced supracondylar humeral fractures in children treated
      operatively at our institution, we identified nine that were completely unstable
      with documented displacement into both flexion and extension as seen on
      fluoroscopic examination with the patient under anesthesia. We used a new
      technique for closed reduction and fixation of these fractures, and then we
      assessed fracture-healing and complications from the injury and treatment.
      RESULTS: All nine fractures were treated satisfactorily with closed reduction and
      percutaneous pinning. The complication rate associated with these unstable
      fractures was no higher than that associated with the 288 more stable fractures.
      Seven of the nine fractures were stabilized with lateral entry pin placement, and
      two fractures were stabilized with crossed medial and lateral pins. None of the
      patients had a nonunion, cubitus varus, malunion, additional surgery, or loss of
      motion. CONCLUSIONS: In rare supracondylar fractures in children,
      multidirectional instability results in displacement into flexion and/or
      extension. This fracture can be classified as type IV according to the Gartland
      system, as it is less stable than a Gartland type-III extension supracondylar
      fracture. These fractures can be treated successfully with a new technique of
      closed reduction and percutaneous pinning, thus avoiding open reduction.

PMID- 16651573
TI  - Long-term follow-up of patients with clubfeet treated with extensive soft-tissue
      release.
AB  - BACKGROUND: Although long-term follow-up studies have shown favorable results, in
      terms of foot function, after treatment of idiopathic clubfoot with serial
      manipulations and casts, we know of no long-term follow-up studies of patients in
      whom clubfoot was treated with an extensive surgical soft-tissue release.
      METHODS: Forty-five patients (seventy-three feet) in whom idiopathic clubfoot was
      treated with either a posterior release and plantar fasciotomy (eight patients)
      or an extensive combined posterior, medial, and lateral release (thirty-seven
      patients) were followed for a mean of thirty years. Patients were evaluated with
      detailed examination of the lower extremities, a radiographic evaluation that
      included grading of osteoarthritis, and three independent quality-of-life
      questionnaires, including the Short Form-36 Medical Outcomes Study. RESULTS: At
      the time of follow-up, the majority of patients in both treatment groups had
      significant limitation of foot function, which was consistent across the three
      independent quality-of-life questionnaires. No significant difference between
      groups was noted with regard to the results of the quality-of-life measures, the
      range of motion of the ankle or the position of the heel, or the radiographic
      findings. Six patients who had been treated with only one surgical procedure had
      better ranges of motion of the ankle and subtalar joints (p < 0.004) than those
      who had had multiple surgical procedures. CONCLUSIONS: Many patients with
      clubfoot treated with an extensive soft-tissue release have poor long-term foot
      function. We found a correlation between the extent of the soft-tissue release
      and the degree of functional impairment. Repeated soft-tissue releases can result
      in a stiff, painful, and arthritic foot and significantly impaired quality of
      life.

PMID- 16651574
TI  - Risk factors for respiratory failure following operative stabilization of
      thoracic and lumbar spine fractures.
AB  - BACKGROUND: Respiratory failure is a serious complication that can adversely
      affect the hospital course and survival of multiply injured patients. Some
      studies have suggested that delayed surgical stabilization of spine fractures may
      increase the incidence of respiratory complications. However, the authors of
      these studies analyzed small sets of patients and did not assess the independent
      effects of multiple risk factors. METHODS: A retrospective cohort study was
      conducted at a regional level-I trauma center to identify risk factors for
      respiratory failure in patients with surgically treated thoracic and lumbar spine
      fractures. Demographic, diagnostic, and procedural variables were identified. The
      incidence of respiratory failure was determined in an adult respiratory distress
      syndrome registry maintained concurrently at the same institution. Univariate and
      multivariate analyses were used to determine independent risk factors for
      respiratory failure. An algorithm was formulated to predict respiratory failure.
      RESULTS: Respiratory failure developed in 140 of the 1032 patients in the study
      cohort. Patients with respiratory failure were older; had a higher mean Injury
      Severity Score (ISS) and Charlson Comorbidity Index Score; had greater incidences
      of pneumothorax, pulmonary contusion, and thoracic level injury; had a lower mean
      Glasgow Coma Score (GCS); were more likely to have had a posterior surgical
      approach; and had a longer mean time from admission to surgical stabilization
      than the patients without respiratory failure (p < 0.05). Multivariate analysis
      identified five independent risk factors for respiratory failure: an age of more
      than thirty-five years, an ISS of > 25 points, a GCS of < or = 12 points, blunt
      chest injury, and surgical stabilization performed more than two days after
      admission. An algorithm was created to determine, on the basis of the number of
      preoperative predictors present, the relative risk of respiratory failure when
      surgery was delayed for more than two days. CONCLUSIONS: Independent risk factors
      for respiratory failure were identified in an analysis of a large cohort of
      patients who had undergone operative stabilization of thoracic and lumbar spine
      fractures. Early operative stabilization of these fractures, the only risk factor
      that can be controlled by the physician, may decrease the risk of respiratory
      failure in multiply injured patients.

PMID- 16651575
TI  - The press-fit condylar modular total knee system with a posterior cruciate
      substituting design. A concise follow-up of a previous report.
AB  - The purpose of the present study was to determine the long-term results of a
      series of 150 consecutive primary posterior stabilized modular knee
      arthroplasties that had been performed in 118 patients with use of a
      circumferential tibial insert capture as described in a previous report,
      published in 1997. The patients were evaluated with use of a patient-administered
      questionnaire; Knee Society clinical, functional, and radiographic scoring
      systems; and Kaplan-Meier survivorship analysis. A good to excellent result was
      confirmed in seventy-six (90%) of the eighty-four patients (105 knees) with a
      mean duration of follow-up of twelve years (range, ten to thirteen years). At
      twelve years, the survival rate was 94.6% +/- 4.0% with failure for any reason as
      the end point and 98.3% +/- 2.4% with mechanical failure as the end point.
      Revision surgery was performed in five knees because of infection (two knees),
      dislocation (one knee), and substantial polyethylene wear with femoral osteolysis
      (two knees). We concluded that, while fixation failure is rare, polyethylene wear
      and osteolysis are emerging as important causes of failure.

PMID- 16651576
TI  - Mechanical distraction for the treatment of posttraumatic stiffness of the elbow
      in children and adolescents.
AB  - BACKGROUND: Elbow contracture is a recognized sequela of elbow injuries in
      children and adolescents, but previous studies of operative treatment with formal
      capsular release have demonstrated unpredictable outcomes and unfavorable
      results. METHODS: Over a period of five years, fourteen children and adolescents
      with a mean age of fourteen years who had posttraumatic stiffness of the elbow
      were managed according to a prospective protocol. Eleven patients had undergone a
      mean of three previous operative procedures before the index operation. After
      intraoperative distraction with an external fixator, there was a relaxation phase
      for six days followed by mobilization of the elbow joint under distraction in the
      fixator for a mean of seven weeks. Intraoperative range of motion under
      distraction reached a mean of 100 degrees. Open arthrolysis was not performed,
      but in four children impinging heterotopic bone was removed through a limited
      approach. Decompression of the ulnar nerve was performed in seven patients.
      RESULTS: The mean preoperative arc of total elbow motion was 37 degrees. The mean
      pronation was 46 degrees, and the mean supination was 56 degrees. After a mean
      duration of follow-up of thirty-four months, all patients but two had achieved a
      functional arc of motion of 100 degrees. The mean arc of flexion-extension was
      108 degrees (range, 75 degrees to 130 degrees). The mean range of pronation was
      73 degrees (range, 20 degrees to 90 degrees), and the mean range of supination
      was 75 degrees (range, 10 degrees to 90 degrees). There were no pin-track
      infections or deep infections, and all elbows were stable. At the time of follow
      up, three patients had radiographic evidence of humeroulnar degeneration.
      CONCLUSIONS: Closed distraction of the elbow joint with use of a monolateral
      external fixation frame with motion capacity yields more favorable results than
      other previously reported options for the treatment of posttraumatic elbow
      contractures in children and adolescents.

PMID- 16651577
TI  - Thoracoscopic spinal fusion compared with posterior spinal fusion for the
      treatment of thoracic adolescent idiopathic scoliosis.
AB  - BACKGROUND: Posterior spinal fusion with segmental instrumentation is the gold
      standard for the surgical treatment of thoracic adolescent idiopathic scoliosis.
      More recently, anterior surgery and video-assisted thoracoscopic surgery with
      spinal instrumentation have become available. The purpose of the present study
      was to compare the radiographic and clinical outcomes as well as pulmonary
      function in patients managed with either anterior thoracoscopic or posterior
      surgery. METHODS: Radiographic data, Scoliosis Research Society patient-based
      outcome questionnaires, pulmonary function, and operative records were reviewed
      for fifty-one patients undergoing surgical treatment of scoliosis. Data were
      collected preoperatively, immediately postoperatively, and at the time of the
      final follow-up. The radiographic parameters that were analyzed included coronal
      curve correction, the most caudad instrumented vertebra tilt angle correction,
      coronal balance, and thoracic kyphosis. The operative parameters that were
      evaluated included the operative time, the estimated blood loss, the blood
      transfusion rate, the number of levels fused, the type of bone graft used, and
      the number of intraoperative and postoperative complications. The pulmonary
      function parameters that were analyzed included vital capacity and peak flow.
      RESULTS: The thoracoscopic group included twenty-eight patients with a mean age
      of 14.6 years, and the posterior fusion group included twenty-three patients with
      a mean age of 14.3 years. The percent correction was 54.5% for the thoracoscopic
      group and 55.3% for the posterior group. With the numbers available, there were
      no significant differences between the two groups in terms of kyphosis (p =
      0.84), coronal balance (p = 0.70), or tilt angle (p = 0.91) at the time of the
      final follow-up. The mean number of levels fused was 5.8 in the thoracoscopic
      group, compared with 9.3 levels in the posterior group (p < 0.0001). The
      estimated blood loss in the thoracoscopic group was significantly less than that
      in the posterior fusion group (361 mL compared with 545 mL; p = 0.03), and the
      transfusion rate in the thoracoscopic group was significantly lower than that in
      the posterior fusion group (14% compared with 43%; p = 0.01). Operative time in
      the thoracoscopic group was significantly greater than that in the posterior
      group (6.0 compared with 3.3 hours, p < 0.0001). There were no intraoperative
      complications in either group. Vital capacity and peak flow had returned to
      baseline levels in both groups at the time of the final follow-up. Patients in
      the thoracoscopic group scored higher than those in the posterior group in terms
      of the total score (p < 0.0001) and all of the domains (p < 0.01) of the
      Scoliosis Research Society questionnaire at the time of the final follow-up.
      CONCLUSIONS: Thoracoscopic spinal instrumentation compares favorably with
      posterior fusion in terms of coronal plane curve correction and balance, sagittal
      contour, the rate of complications, pulmonary function, and patient-based
      outcomes. The advantages of the procedure include the need for fewer levels of
      spinal fusion, less operative blood loss, lower transfusion requirements, and
      improved cosmesis as a result of small, well-hidden incisions. However, the
      operative time for the thoracoscopic procedure was nearly twice that for the
      posterior approach. Additional study is needed to determine the precise role of
      thoracoscopic spinal instrumentation in the treatment of thoracic adolescent
      idiopathic scoliosis.

PMID- 16651578
TI  - The effect of derotational humeral osteotomy on global shoulder function in
      brachial plexus birth palsy.
AB  - BACKGROUND: Derotational humeral osteotomies have been used in older children
      with brachial plexus birth palsy and glenohumeral joint deformity to place the
      upper extremity in a more functional position. The purpose of this study was to
      determine the effects of these procedures on shoulder function and joint
      morphology. METHODS: Forty-three patients underwent a derotational humeral
      osteotomy for functional impairment in the setting of internal rotation
      contracture and/or glenohumeral joint deformity at our institution from 1996 to
      2004. Osteotomies were performed proximal to the deltoid insertion and were
      stabilized with plate-and-screw fixation. The average age of the patients at the
      time of surgery was 7.6 years (range, 2.3 to 17.0 years). Shoulder function was
      graded according to the modified Mallet classification system. Glenohumeral
      deformity was graded according to the classification scheme of Waters et al. The
      results for twenty-seven patients who were followed for a minimum of two years
      (average, 3.7 years) are reported. RESULTS: The average amount of external
      rotation achieved with osteotomy was 64 degrees (range, 35 degrees to 90
      degrees). The mean aggregate Mallet classification score improved from 13 to 18
      points (p < 0.01). The mean Mallet classification scores for the individual
      elements similarly demonstrated improvement following osteotomy, with the
      greatest gains in hand-to-mouth, hand-to-neck, and external rotation motions. The
      mean classification of the glenohumeral deformity was type IV preoperatively and
      postoperatively, signifying the persistence of glenohumeral dysplasia. There were
      no nonunions. One patient required a revision osteotomy for inadequate initial
      correction. One patient sustained a humeral fracture distal to the plate fixation
      because of sports-related trauma. CONCLUSIONS: Derotational humeral osteotomy
      improves shoulder function in patients with brachial plexus birth palsy, internal
      rotation contracture, and/or advanced glenohumeral joint deformity. This
      osteotomy provides an attractive treatment option for patients with brachial
      plexus birth palsy who have advanced glenohumeral dysplasia precluding soft
      tissue releases and tendon transfers.

PMID- 16651579
TI  - Lumbar hemivertebra resection.
AB  - BACKGROUND: A single lumbar hemivertebra can be expected to cause progressive
      scoliosis. The aim of this study was to evaluate the results of a lumbar
      hemivertebra resection and short-segment fusion through a combined posterior and
      anterior approach. METHODS: From 1987 to 2002, a consecutive series of twenty-one
      patients with congenital scoliosis or kyphoscoliosis due to a lumbar hemivertebra
      were managed by resection of the hemivertebra through a combined posterior and
      anterior approach and with the use of a short anterior and posterior convex-side
      fusion. RESULTS: The mean age at the time of surgery was 3.3 years (range, twelve
      months to 10.2 years). The mean followup period was 8.6 years. There was a mean
      improvement of 71.4% in the segmental scoliosis curve from a mean angle of 32.9
      degrees before surgery to 9.4 degrees at the time of the latest follow-up
      assessment, and a mean improvement of 63.9% in the global scoliosis curve from
      34.1 degrees to 12.3 degrees. The mean final lordosis was within normal values.
      CONCLUSIONS: Excision of a lumbar hemivertebra is safe and provides stable
      correction when combined with a short-segment fusion. Surgery should be performed
      as early as possible to avert the development of severe local deformities and
      prevent secondary structural deformities that would require a more extensive
      fusion later.

PMID- 16651580
TI  - Up-regulation of bone morphogenetic proteins in cultured murine bone cells with
      use of specific electric fields.
AB  - BACKGROUND: Capacitively coupled electric stimulation has been successfully used
      in the treatment of bone nonunions and to effect spinal fusions. However, the
      pathway of biologic events whereby this is accomplished has not been fully
      elucidated. To determine whether bone morphogenetic proteins (BMPs) could be
      involved, the effect of electrical stimulation on BMP gene expression was
      investigated. METHODS: Postconfluent cultures of MC3T3-E1 bone cells were exposed
      to a series of capacitively coupled signals in which the duration, amplitude,
      frequency, and duty cycle were sequentially and systematically varied. The
      cellular response was measured by quantifying the mRNA levels of BMP-2 through
      BMP-8, as well as the BMP antagonists gremlin and noggin, with use of reverse
      transcription followed by real-time quantitative polymerase chain reaction. BMP-2
      protein was measured by enzyme-linked immunosorbent assay, and alkaline
      phosphatase activity was measured by a specific colorimetric assay. RESULTS: The
      results showed that BMP-2 through BMP-8, gremlin, and noggin were all normally
      expressed by MC3T3-E1 cells, and could be significantly up-regulated by specific
      and selective capacitively coupled electric fields (p < 0.05). However, mRNA
      expression for BMP-2, 4, 5, 6, and 7 was consistently up-regulated several times
      higher than that for BMP-3 and BMP-8, gremlin, and noggin under identical
      conditions. Concomitantly, BMP-2 protein production and alkaline phosphatase
      activity were both significantly increased in the same electrically stimulated
      cultures (p = 0.001 and p < 0.01, respectively). CONCLUSIONS: These data clearly
      show that our optimal capacitively coupled signal (60 kHz, 20 mV/cm at a 50% duty
      cycle for twenty-four hours) can specifically, selectively, and simultaneously up
      regulate the expression of a number of osteoinductive BMPs; other BMPs and
      antagonists are only moderately affected.

PMID- 16651581
TI  - Proximal deep vein thrombosis after hip replacement for oncologic indications.
AB  - BACKGROUND: Patients with cancer who undergo surgery about the hip are at
      increased risk for the development of deep vein thrombosis. We implemented a
      program of chemical and mechanical prophylaxis to prevent this problem. This
      study was performed to assess the effectiveness of that program. METHODS: Eighty
      seven consecutive patients with an active malignant tumor who underwent hip
      replacement surgery at our institution over a two-year period were included in
      the study. All patients were treated with intermittent pneumatic compression
      devices. Seventy-eight patients received anticoagulants, and nine did not.
      Postoperative surveillance for proximal deep vein thrombosis was routinely
      performed on all patients with duplex Doppler ultrasonography. RESULTS: Four
      patients had proximal deep vein thrombosis, and one patient, who did not receive
      anticoagulation, had a nonfatal pulmonary embolism. The use of prophylactic low
      molecular-weight heparin (dalteparin) was associated with a 4% rate of proximal
      deep vein thrombosis (three of seventy-eight patients). Proximal deep vein
      thrombosis developed in three of eight patients with pelvic disease, one of
      nineteen patients with femoral disease, and zero of sixty patients with hip
      disease (p < 0.00001). The prevalence of proximal deep vein thrombosis was
      significantly higher (p < 0.02) following replacements in patients with sarcoma
      (three of twenty-one) than it was after replacements in patients with carcinoma
      (zero of fifty-seven) or hematologic malignant disease (one of nine). On
      multivariate analysis, only the location of the disease (the pelvis, femur, or
      hip) was found to be independently significant for an association with deep vein
      thrombosis. A wound complication developed in four of twenty-one patients with
      sarcoma and no patient with carcinoma or hematologic malignant disease (p <
      0.001). The pathologic type was the only factor studied that was independently
      significant for an association with wound complications on multivariate analysis.
      CONCLUSIONS: The rate of proximal deep vein thrombosis in patients who had
      undergone hip replacement for oncologic indications was low when the use of an
      intermittent pneumatic compression device was supplemented with prophylaxis with
      low-molecular-weight heparin.

PMID- 16651582
TI  - Viscoelasticity and temperature variations decrease tension and stiffness of
      hamstring tendon grafts following anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Hamstring tendon grafts used for anterior cruciate ligament
      reconstruction are typically harvested early in the surgical procedure and are
      preconditioned prior to reimplantation. Postoperatively, the grafts undergo
      stress relaxation and warm from the temperature of the operating room to body
      temperature. The hypothesis of this study was that the tension within
      semitendinosus and gracilis tendon grafts and the stiffness of the grafts
      significantly decrease postoperatively because of both stress relaxation and an
      increase in temperature. METHODS: Double-strand grafts were created from six
      semitendinosus tendons and six gracilis tendons harvested from cadaver specimens.
      The grafts were loaded to 65 N while at operating-room temperature (20 degrees
      C). After fifteen minutes of stress relaxation, graft tension was measured and
      the grafts were stretched by 0.1 mm to determine stiffness. The tension and
      stiffness measurements represented graft properties immediately following
      reconstruction. Additional tension and stiffness measurements were made following
      three hours of stress relaxation and after increasing the temperature to the body
      temperature at the knee (34 degrees C). Both types of graft were examined for
      differences in stiffness and tension due to stress relaxation and the temperature
      increase. RESULTS: For both types of graft, the tension and stiffness decreased
      following stress relaxation to approximately 50% and 80%, respectively, of the
      value immediately after reconstruction. Increasing the temperature decreased the
      tension and stiffness further to approximately 40% and 70%, respectively, of the
      value after reconstruction for both types of graft. All changes in tension and
      stiffness were significant (p < 0.01). CONCLUSIONS: Graft tension and stiffness
      achieved immediately following reconstruction are not maintained postoperatively
      because of stress relaxation and a temperature increase. This could lead to
      increased knee laxity.

PMID- 16651583
TI  - Revision total hip arthroplasty with a custom cementless stem with distal cross
      locking screws. Early results in femora with large proximal segmental
      deficiencies.
AB  - BACKGROUND: Revision total hip arthroplasty in the setting of a large proximal
      segmental femoral deficiency and/or discontinuity between the proximal and distal
      parts of the femur remains a challenging problem. We describe the use of a
      cementless stem with distal cross-locking screws to provide stability of the
      femoral implant in this situation. METHODS: Seventeen custom fully porous and
      hydroxyapatite-coated titanium femoral stems with distal cross-locking titanium
      screws were implanted in sixteen patients during revision total hip arthroplasty.
      Preoperatively, all of the patients had Paprosky grade-IIIB or IV femoral
      deficiencies. At the time of follow-up, the Harris hip scores were calculated and
      radiographs were made. A successful result was defined as a postoperative
      increase in the Harris hip score of >20 points, a radiographically stable
      implant, and no additional femoral reconstruction. RESULTS: At the time of final
      follow-up, at a mean of 5.3 years postoperatively, the result was successful in
      sixteen of the seventeen hips, the mean Harris hip score had improved from 35 to
      76 points, and all implants were clinically and radiographically stable. There
      were no postoperative infections or hip dislocations. CONCLUSIONS: The use of a
      custom femoral stem with distal cross-locking screws can provide at least
      intermediate-term clinical and radiographic stability in patients with Paprosky
      grade-IIIB or IV femoral deficiencies. Longer follow-up will be required to
      determine the longevity of these implants.

PMID- 16651584
TI  - Pathoanatomy of posterior malleolar fractures of the ankle.
AB  - BACKGROUND: The functional outcome following ankle fractures that involve a
      posterior malleolar fragment is often not satisfactory, and treatment of this
      type of fracture remains controversial. Thorough knowledge of the pathologic
      anatomy of the posterior malleolar fracture is essential for planning appropriate
      treatment. Thus, we conducted a computed tomographic study to clarify the
      pathologic anatomy of the posterior malleolar fracture. METHODS: Between 1999 and
      2003, fifty-seven consecutive patients with a unilateral ankle fracture with one
      or more posterior fragments were managed at our hospital. We reviewed the
      patients' preoperative computed tomographic scans to determine (1) the ratio of
      the posterior fragment area to the total cross-sectional area of the tibial
      plafond and (2) the angle between the bimalleolar axis and the major fracture
      line of the posterior malleolus. Each fracture was categorized according to the
      location of the major fracture line on the computed tomographic image at the
      level of the tibial plafond. RESULTS: The fifty-seven fractures were categorized
      into three types: (1) the posterolateral-oblique type (thirty-eight fractures;
      67%), (2) the medial-extension type (eleven fractures; 19%), and (3) the small
      shell type (eight fractures; 14%). Two of the eleven medial-extension fractures
      extended to the anterior part of the medial malleolus. A total of nine of the
      eleven medial-extension fractures actually consisted of two fragments [corrected]
      The conditions are not exclusive of one another; for example, in the case of one
      of the fractures exhibiting two fragments, the fracture also extended to the
      anterior part of the medial malleolus [corrected] The average area of the
      fragment comprised 11.7% of the cross-sectional area of the tibial plafond for
      posterolateral-oblique fractures and 29.8% for medial-extension fractures. In the
      cases of seven of the nine fractures that comprised >25% of the tibial plafond,
      the fracture line extended to the medial malleolus. The angles between the
      bimalleolar axis and the major fracture line of the posterior malleolus varied.
      CONCLUSIONS: The fracture lines associated with posterior malleolar fractures
      appear to be highly variable. A large fragment extending to the medial malleolus
      existed in almost 20% of the posterior malleolar fractures in the current study,
      and some fragments involved almost the entire medial malleolus. Because of the
      great variation in fracture configurations, preoperative use of computed
      tomography may be justified. The information obtained from this study will be
      helpful for conducting basic research of this condition and for determining
      appropriate surgical approaches.

PMID- 16651585
TI  - Spinal implants and radiation therapy: the effect of various configurations of
      titanium implant systems in a single-level vertebral metastasis model.
AB  - BACKGROUND: The combination of surgery and radiation therapy is a common clinical
      practice in the treatment of spinal tumors. Although it is known that metallic
      implants disturb radiation therapy beams, it is not known what kind of dose
      distributions appear with spinal irradiation in the presence of a spinal implant.
      The aim of the present study was to investigate the effect of various spinal
      implant constructs on the dose of radiation delivered to the spinal canal in a
      single-level metastasis model. METHODS: We performed four spinal implant
      reconstructions on standard sawbones spine models: posterior instrumentation
      without anterior column reconstruction, posterior instrumentation with anterior
      column reconstruction with use of a titanium cage, anterior instrumentation with
      anterior column reconstruction with use of a titanium cage, and anterior
      instrumentation with anterior column reconstruction with use of chest tubes
      filled with bone cement. Irradiation with two different radiation therapy units
      (a cobalt-60 teletherapy unit and a linear accelerator) was performed twice for
      each model in a posterior-to-anterior direction, and thermoluminescent dosimeters
      were used to measure the dose changes in the anterior, middle, and posterior
      portions of the spinal canal. RESULTS: Compared with the sawbones-only model, the
      posterior instrumentation reconstructions resulted in a 5% to 7% decrease in the
      radiation dose delivered to the spinal canal with both radiation therapy units,
      whereas the anterior instrumentation reconstructions resulted in a 1% decrease in
      the dose delivered with the linear accelerator unit and a < or = 2% increase in
      the dose delivered with the cobalt-60 teletherapy unit. When thermoluminescent
      dosimeters in the middle of the spinal canal were evaluated individually,
      anterior instrumentation with anterior column reconstruction with use of bone
      cement-filled chest tubes resulted in a 5.5% increase in the radiation dose
      delivered with the cobalt-60 teletherapy unit, whereas all of the other
      instrumentation models resulted in a <1% disturbance in the radiation dose
      delivered with both radiation therapy units. CONCLUSIONS: The posterior
      instrumentation systems did not result in the delivery of an increased dose of
      radiation to the spinal cord, suggesting that current radiation therapy regimens
      may be performed without additional harm. The anterior instrumentation systems
      also appeared to be relatively safe when irradiation was performed with the
      linear accelerator unit. However, when irradiation was performed with use of the
      cobalt-60 teletherapy unit, there was an increase in the dose of radiation
      delivered to the spinal canal in the presence of the anterior instrumentation
      systems, particularly the anterior column reconstruction with use of bone cement
      filled chest tubes. These dose-perturbation characteristics might be important to
      consider during the calculation of radiation therapy protocols for patients who
      are going to receive high doses or recurrent treatments that would reach the
      tolerance limits of the spinal cord.

PMID- 16651586
TI  - Skeletal tuberculosis following fracture fixation. A report of five cases.

PMID- 16651587
TI  - Necrotizing fasciitis caused by methicillin-resistant Staphylococcus aureus
      resulting in death. A report of three cases.

PMID- 16651588
TI  - Maisonneuve fracture equivalent with proximal tibiofibular dislocation. A case
      report and literature review.

PMID- 16651589
TI  - Nontraumatic osteonecrosis of the femoral head: ten years later.
AB  - The etiology of osteonecrosis of the hip may have a genetic basis. The
      interaction between certain risk factors and a genetic predisposition may
      determine whether this disease will develop in a particular individual. The
      rationale for use of joint-sparing procedures in the treatment of this disease is
      based on radiographic measurements and findings with other imaging modalities.
      Early diagnosis and intervention prior to collapse of the femoral head is key to
      a successful outcome of joint-preserving procedures. The results of joint
      preserving procedures are less satisfactory than the results of total hip
      arthroplasty for femoral heads that have already collapsed. New pharmacological
      measures as well as the use of growth and differentiation factors for the
      prevention and treatment of this disease may eventually alter our treatment
      approach, but it is necessary to await results of clinical research with long
      term follow-up of these patients.

PMID- 16651590
TI  - Failed spine surgery syndrome in the life and career of John Fitzgerald Kennedy.

PMID- 16651591
TI  - Antimicrobial prophylaxis to prevent surgical site infection.

PMID- 16651592
TI  - An AOA critical issue. Should there be a minimal surgical experience for a
      graduating orthopaedic surgery resident?

PMID- 16651593
TI  - Efficacy of surgical preparation solutions in foot and ankle surgery.

PMID- 16651595
TI  - Treatment of acute Achilles tendon ruptures. A meta-analysis of randomized,
      controlled trials.

PMID- 16651597
TI  - Revised grades of recommendation for summaries or reviews of orthopaedic surgical
      studies.

PMID- 16651600
TI  - Femoral component revision with use of impaction bone-grafting and a cemented
      polished stem.

PMID- 16651602
TI  - Oral direct thrombin inhibitor ximelagatran compared with warfarin for the
      prevention of venous thromboembolism after total knee arthroplasty.

PMID- 16651604
TI  - Accuracy in the measurement of compartment pressures: a comparison of three
      commonly used devices.

PMID- 16651605
TI  - Continuous passive motion after surgery in infants with clubfoot led to greater
      short-term but not long-term improvement relative to standard immobilization.

PMID- 16651606
TI  - Total disc replacement with the CHARITE artificial disc was as effective as
      lumbar interbody fusion.

PMID- 16651607
TI  - Direct decompressive surgery and radiation therapy improved walking ability in
      metastatic epidural spinal cord compression.

PMID- 16651608
TI  - Cancer interaction with the bone microenvironment: a workshop of the National
      Institutes of Health Tumor Microenvironment Study Section.

PMID- 16651609
TI  - Attenuation of folic acid-induced renal inflammatory injury in platelet
      activating factor receptor-deficient mice.
AB  - Platelet-activating factor (PAF), a potent lipid mediator with various biological
      activities, plays an important role in inflammation by recruiting leukocytes. In
      this study we used platelet-activating factor receptor (PAFR)-deficient mice to
      elucidate the role of PAF in inflammatory renal injury induced by folic acid
      administration. PAFR-deficient mice showed significant amelioration of renal
      dysfunction and pathological findings such as acute tubular damage with
      neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2
      hexenal (day 2), and interstitial fibrosis with macrophage infiltration
      associated with expression of monocyte chemoattractant protein-1 and tumor
      necrosis factor-alpha in the kidney (day 14). Acute tubular damage was attenuated
      by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the
      contribution of neutrophils to acute phase injury. Macrophage infiltration was
      also decreased when treatment with a PAF antagonist (WEB2086) was started after
      acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that
      PAF exhibits a strong chemotactic activity for macrophages. These results
      indicate that PAF is involved in pathogenesis of folic acid-induced renal injury
      by activating neutrophils in acute phase and macrophages in chronic interstitial
      fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from
      inflammatory cells.

PMID- 16651610
TI  - Antigen and lipopolysaccharide play synergistic roles in the effector phase of
      airway inflammation in mice.
AB  - T helper (Th) cells play major roles in orchestrating asthmatic airway
      inflammation, but the molecular mechanisms controlling Th-cell recruitment to the
      airways remain incompletely defined. Innate immunity contributes importantly to
      the recruitment of effector T cells into sites of inflammation. To understand
      better the role of innate immune signals in the development of airway
      inflammation, we used a murine model in which lipopolysaccharide (LPS)
      contaminating the antigen is thought to trigger Toll-like receptor 4 (TLR4). To
      investigate the importance of the TLR4-signaling pathway in induction of lung
      inflammation, we compared recruitment of adoptively transferred ovalbumin
      specific Th1 and Th2 cells in wild-type and TLR4 mutant (TLR4m) mice after
      intranasal or aerosol challenge. Intranasal challenge of TLR4m mice with
      ovalbumin resulted in decreased recruitment of Th1 and Th2 cells compared with
      that of wild-type mice. The numbers of Th1 and Th2 cells recruited to the airways
      of TLR4m mice were less profoundly reduced after aerosol ovalbumin challenge.
      Comparing the effects of altering the dose of ovalbumin with that of LPS
      suggested that both contribute to the magnitude of the response in wild-type
      mice. Our findings demonstrate the importance of both antigen and endotoxin
      acting in a synergistic manner in the development of airway inflammation.

PMID- 16651611
TI  - Rapid fatty acid ethyl ester synthesis by porcine myocardium upon ethanol
      infusion into the left anterior descending coronary artery.
AB  - Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been
      implicated in ethanol-induced heart injury. To assess the in vivo production of
      FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in
      pigs. A controlled 60-minute ethanol infusion was administered into the distal
      left anterior descending coronary artery in seven swine; serial blood sampling of
      the coronary sinus and peripheral vein before, during, and after infusion allowed
      measurement of FAEE production and ethanol levels in the coronary sinus and the
      peripheral circulation. In a single animal, FAEEs were also quantified from nine
      different sites within the myocardium. FAEEs were produced by the heart within 5
      minutes of exposure to ethanol, with very high concentrations of FAEEs detected
      in coronary sinus blood. Significant variability in amounts of FAEEs was detected
      in different regions of the heart tissue. A strong correlation was found between
      coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE
      production by the heart after delivery of ethanol into the left anterior
      descending coronary artery was rapid, reaching levels in the coronary sinus blood
      4 to 10 times greater than that found in peripheral blood after ethanol intake.
      These data demonstrate that FAEEs may be mediators of ethanol-induced
      cardiotoxicity.

PMID- 16651612
TI  - The mitochondrial K-ATP channel opener, diazoxide, prevents ischemia-reperfusion
      injury in the rabbit spinal cord.
AB  - Paraplegia resulting from ischemia is a catastrophic complication of
      thoracoabdominal aortic surgery. The current study was designed to investigate
      the effects of diazoxide (DZ) on mitochondrial structure, neurological function,
      DNA damage-repair, and apoptosis in spinal cord ischemia-reperfusion injury.
      Rabbits were subjected to 30 minutes of spinal cord ischemia and reperfusion (1
      hour) with or without diazoxide (n = 6 in each group) by clamping and releasing
      the infrarenal aorta. The neurological functional score was significantly
      improved in the DZ-treated ischemia-reperfusion injury group. Electron
      microscopic studies demonstrated that mitochondrial damage in the spinal cord
      after injury was significantly reduced by DZ. Mitochondrial superoxide and
      hydrogen peroxide levels were also markedly decreased in the DZ-treated injury
      group compared with the untreated group. DZ decreased levels of the oxidative DNA
      damage product 8-oxoG and increased levels of the DNA repair enzyme OGG-1.
      Furthermore, DZ inhibited apoptosis via caspase-dependent and -independent
      pathways. These studies indicate for the first time that the mitochondrial K-ATP
      channel opener diazoxide improves neurological function after spinal cord
      ischemia and reperfusion by diminishing levels of reactive oxygen species,
      decreasing DNA oxidative damage, and inhibiting caspase-dependent and 
      independent apoptotic pathways while preserving mitochondrial structure.

PMID- 16651613
TI  - SUMOylation attenuates sensitivity toward hypoxia- or desferroxamine-induced
      injury by modulating adaptive responses in salivary epithelial cells.
AB  - Hypoxic stress activates various signal transduction pathways including
      posttranslational modification with the ubiquitin-like SUMO protein
      (SUMOylation). However, the molecular mechanisms by which SUMOylation regulates
      hypoxic responses remain unclear. Here, we investigated the ability of rat
      salivary Pa-4 epithelial cells to resist cell injury elicited by 1% O(2)- or
      hypoxia-mimetic desferroxamine (DFO)-stimulated SUMOylation processes. By using
      Pa-4 cells stably transduced with lenti-SUMO-1 and a cell-permeant peptide
      harboring SUMO-binding motif to interfere with SUMO-dependent protein-protein
      interactions, we demonstrate that SUMOylation augments cell survival against DFO
      treatment. This appeared to be partly mediated through attenuation of Protein
      Kinase C (PKC)-delta activation and caspase-3 cleavage, hallmarks of pro
      apoptotic signaling. Intriguingly, DFO-induced phosphorylation of DNA damage
      marker ataxia-telangiectasia-mutated protein S1981 preceded activation of
      PKCdelta and caspase-3. Constitutive SUMOylation facilitated 1% O(2)- or DFO
      induced nuclear factor kappaB transactivation, possibly via activation of
      genotoxic signaling cascade. In addition, we observed transient preservation of
      transepithelial electrical resistance during the early stage of hypoxia (1% O(2))
      as well as enhanced transepithelial electrical resistance recovery after
      prolonged hypoxia in SUMO-1-expressing cell monolayers. In conclusion, our
      results unveil a previously unrecognized mechanism by which SUMOylation and
      activation of ataxia-telangiectasia-mutated protein, PKCdelta, caspase-3, and
      nuclear factor kappaB signaling pathways modulate salivary adaptive responses to
      stress in cells exposed to either 1% O(2) or DFO.

PMID- 16651614
TI  - Deleterious role of IFNgamma in a toxic model of central nervous system
      demyelination.
AB  - Interferon-gamma (IFNgamma) is a pleiotropic cytokine that plays an important
      role in many inflammatory processes, including autoimmune diseases such as
      multiple sclerosis (MS). Demyelination is a hallmark of MS and a prominent
      pathological feature of several other inflammatory diseases of the central
      nervous system, including experimental autoimmune encephalomyelitis, an animal
      model of MS. Accordingly, in this study we followed the effect of IFNgamma in the
      demyelination and remyelination process by using an experimental autoimmune
      encephalomyelitis model of demyelination/remyelination after exposure of mice to
      the neurotoxic agent cuprizone. We show that demyelination in response to
      cuprizone is delayed in mice lacking the binding chain of IFNgamma receptor. In
      addition, IFNgammaR(-/-) mice exhibited an accelerated remyelination process
      after cuprizone was removed from the diet. Our results also indicate that the
      levels of IFNgamma were able to modulate the microglia/macrophage recruitment to
      the demyelinating areas. Moreover, the accelerated regenerative response showed
      by the IFNgammaR(-/-) mice was associated with a more efficient recruitment of
      oligodendrocyte precursor cells in the demyelinated areas. In conclusion, this
      study suggests that IFNgamma regulates the development and resolution of the
      demyelinating syndrome and may be associated with toxic effects on both mature
      oligodendrocytes and oligodendrocyte precursor cells.

PMID- 16651615
TI  - Heat shock proteins and mitogen-activated protein kinases in steatotic livers
      undergoing ischemia-reperfusion: some answers.
AB  - Ischemic preconditioning protects steatotic livers against ischemia-reperfusion
      (I/R) injury, but just how this is achieved is poorly understood. Here, I/R or
      preconditioning plus I/R was induced in steatotic and nonsteatotic livers
      followed by investigating the effect of pharmacological treatments that modulate
      heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs). MAPKs,
      HSPs, protein kinase C, and transaminase levels were measured after reperfusion.
      We report that preconditioning increased HSP72 and heme-oxygenase-1 (HO-1) at 6
      and 24 hours of reperfusion, respectively. Unlike nonsteatotic livers, steatotic
      livers benefited from HSP72 activators (geranylgeranylacetone) throughout
      reperfusion. This protection seemed attributable to HO-1 induction. In steatotic
      livers, preconditioning and geranylgeranylacetone treatment (which are
      responsible for HO-1 induction) increased protein kinase C activity. HO-1
      activators (cobalt(III) protoporphyrin IX) protected both liver types.
      Preconditioning reduced p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in
      HSP72 induction though HO-1 remained unmodified. Like HSP72, both p38 and JNK
      appeared not to be crucial in preconditioning, and inhibitors of p38 (SB203580)
      and JNK (SP600125) were less effective against hepatic injury than HO-1
      activators. These results provide new data regarding the mechanisms of
      preconditioning and may pave the way to the development of new pharmacological
      strategies in liver surgery.

PMID- 16651616
TI  - Cadherin-11 induces rheumatoid arthritis fibroblast-like synoviocytes to form
      lining layers in vitro.
AB  - The synovial lining of diarthrodial joints is composed of a condensed network of
      synoviocytes that form an intact layer via cell-to-cell contacts with significant
      intercellular matrix spaces. However, the molecular basis for synovial lining
      formation and its structural integrity has not been previously defined. In this
      study, using a three-dimensional fibroblast-like synoviocyte in vitro organ
      culture system, we provide evidence that cadherin-11 expressed in fibroblast-like
      synoviocytes plays a determining role in establishing the synovial lining layer.
      Fibroblast-like synoviocytes that were grown in three-dimensional matrices
      demonstrated formation of a lining structure at the interface between the matrix
      and the fluid phase. Treatment of fibroblast-like synoviocyte organ cultures with
      a cadherin-11-Fc fusion protein efficiently abrogated lining layer organization.
      Moreover, because E-cadherin-expressing fibroblasts failed to organize a lining
      layer structure at the tissue boundary, this effect appears to be a distinct
      characteristic of fibroblasts expressing cadherin-11. We found that cadherin-11
      mediated fibroblast-like synoviocyte cell-to-cell adhesion via formation of
      adherens junctions that were linked to and remodeled the actin cytoskeleton.
      Together, these studies implicate cadherin-11 in synovial tissue and lining layer
      formation and provide an in vitro system to model fibroblast-like synoviocyte
      behavior and function in organizing the synovial tissue.

PMID- 16651617
TI  - Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation.
AB  - Hepatic fibrosis is a common outcome of a variety of chronic liver diseases. Here
      we evaluated the therapeutic efficacy of hepatocyte growth factor (HGF) on liver
      fibrosis induced by bile duct ligation (BDL) and investigated potential
      mechanisms. Mice underwent BDL, followed by intravenous injections of naked HGF
      expression plasmid or control vector. HGF gene therapy markedly ameliorated
      hepatic fibrotic lesions, as demonstrated by reduced alpha-smooth muscle actin
      (alphaSMA) expression, attenuated deposition of type I and type III collagen, and
      normalized total hydroxyproline content. HGF also suppressed transforming growth
      factor-beta1 (TGF-beta1) expression. Interestingly, colocalization of alphaSMA
      and cytokeratin-19 in bile duct epithelium was observed, suggesting the
      possibility of biliary epithelial to myofibroblast transition after BDL. Cells
      that were still positive for cytokeratin-19 but actively producing type I
      collagen were found in the biliary epithelia and periductal region. Laminin
      staining revealed an impaired basement membrane of the bile duct epithelium in
      diseased liver. These lesions were largely prevented by HGF administration. In
      vitro, treatment of human biliary epithelial cells with TGF-beta1 induced
      alphaSMA and fibronectin expression and suppressed cytokeratin-19. HGF abolished
      the phenotypic conversion of biliary epithelial cells induced by TGF-beta1. These
      results suggest that HGF ameliorates hepatic biliary fibrosis in part by blocking
      bile duct epithelial to mesenchymal transition.

PMID- 16651618
TI  - Delineation of matriptase protein expression by enzymatic gene trapping suggests
      diverging roles in barrier function, hair formation, and squamous cell
      carcinogenesis.
AB  - The membrane serine protease matriptase is required for epidermal barrier
      function, hair formation, and thymocyte development in mice, and dysregulated
      matriptase expression causes epidermal squamous cell carcinoma. To elucidate the
      specific functions of matriptase in normal and aberrant epidermal
      differentiation, we used enzymatic gene trapping combined with
      immunohistochemical, ultrastructural, and barrier function assays to delineate
      the spatio-temporal expression and function of matriptase in mouse keratinized
      tissue development, homeostasis, and malignant transformation. In the
      interfollicular epidermis, matriptase expression was restricted to postmitotic
      transitional layer keratinocytes undergoing terminal differentiation. Matriptase
      was also expressed in keratinizing oral epithelium, where it was required for
      oral barrier function, and in thymic epithelium. In all three tissues, matriptase
      colocalized with profilaggrin. In staged embryos, the onset of epidermal
      matriptase expression coincided with that of profilaggrin expression and
      acquisition of the epidermal barrier. In marked contrast to stratifying
      keritinized epithelium, matripase expression commenced already in
      undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and
      displayed hair growth cycle-dependent expression. Exposure of the epidermis to
      carcinogens led to the gradual appearance of matriptase in a keratin-5-positive
      proliferative cell compartment during malignant progression. Combined with
      previous studies, these data suggest that matriptase has diverging functions in
      the genesis of stratified keratinized epithelium, hair follicles, and squamous
      cell carcinoma.

PMID- 16651619
TI  - Mortalin-based cytoplasmic sequestration of p53 in a nonmammalian cancer model.
AB  - In nature the soft shell clam Mya arenaria develops a fatal neoplasm that shares
      molecular similarity with an unrelated group of human cancers. In leukemic clam
      hemocytes, wild-type p53 and mortalin proteins co-localize in the cytoplasm. A
      similar phenotype, characterized by cytoplasmic sequestration of wild-type p53
      protein, has been observed in several human cancers (undifferentiated
      neuroblastoma, retinoblastoma, colorectal and hepatocellular carcinomas, and
      glioblastoma). In some of these cancers p53 is tethered in the cytoplasm by
      mortalin when the latter protein is overexpressed. Using co-immunoprecipitation
      we have demonstrated that mortalin and p53 proteins are complexed in the
      cytoplasm of leukemic clam hemocytes (and not in normal hemocytes). In addition,
      treatment of leukemic clam hemocytes with MKT-077, a cationic inhibitor of
      mortalin, disrupts the interaction of mortalin and p53 proteins, resulting in
      translocation of some p53 to the nucleus. Based on these data, we introduce
      leukemic clam hemocytes as novel and easily accessible, in vivo and in vitro
      models for human cancers displaying a similar mortalin-based phenotype. Treatment
      of these models with novel chemotherapeutics may help reveal the molecular
      mechanism(s) involved in inactivating p53 by this form of cytoplasmic
      sequestration.

PMID- 16651620
TI  - p21Cip1 is required for the development of monocytes and their response to serum
      transfer-induced arthritis.
AB  - One of the central functions of cyclin-dependent kinase inhibitors, such as p21,
      p27, or p16, is to prevent entry into the cell cycle. However, the question
      remains as to whether they have other functions in the cell. We previously
      demonstrated that overexpression of p21 in fibroblasts isolated from patients
      with rheumatoid arthritis decreases the production of pro-inflammatory molecules.
      Overexpression of p21 has been also shown to reduce the development of
      experimental arthritis in mice and rats. To explore the role of endogenous p21 in
      the development of arthritis, we induced arthritis in p21(-/-) mice using the
      K/BxN serum transfer model of arthritis. Mice deficient in p21 were more
      resistant to serum transfer-induced arthritis (K/BxN) than wild-type (wt) control
      mice. Fewer macrophages were detected in p21(-/-) as compared to wt joints
      following transfer of K/BxN serum. Chemotaxis assays of bone marrow-derived
      macrophages from p21(-/-) and wt mice revealed no difference in migration.
      However, there was a substantial decrease in inflammatory monocytes circulating
      in peripheral blood and in monocyte precursors in bone marrow of p21(-/-) mice as
      compared to wt mice. Adoptive transfer of wt bone marrow-derived macrophages into
      p21(-/-) mice restored the sensitivity to serum transfer-induced arthritis. These
      data suggest a novel role for p21 in regulating the development and/or
      differentiation of monocytic populations that are crucial for the induction of
      inflammatory arthritis.

PMID- 16651621
TI  - Ongoing coxsackievirus myocarditis is associated with increased formation and
      activity of myocardial immunoproteasomes.
AB  - A growing body of evidence indicates that viral infections of the heart
      contribute to ongoing myocarditis and dilated cardiomyopathy. Murine models of
      coxsackievirus B3 (CVB3)-induced myocarditis mimic the human disease and allow
      identification of susceptibility factors that modulate the course of viral
      myocarditis. Susceptible mouse strains develop chronic myocarditis on the basis
      of restricted viral replication, whereas resistant strains recover after
      successful virus elimination. In comparative whole-genome microarray analyses of
      infected hearts, several genes involved in the processing and presentation of
      viral epitopes were found to be uniformly up-regulated in acutely CVB3-infected
      susceptible mice compared with resistant animals. In particular, expression of
      the catalytic subunits LMP2, LMP7, and MECL-1, immunoproteasome proteins
      important in the generation of major histocom-patibility complex (MHC) class I
      restricted peptides, was clearly enhanced in the susceptible host. Increased
      expression resulted in enhanced formation of immunoproteasomes and altered
      proteolytic activities of proteasomes in the heart. This was accompanied by a
      concerted up-regulation of the antigen-presenting machinery in susceptible mice.
      Thus, we propose that increased formation of immunoproteasomes in susceptible
      mice affects the generation of antigenic peptides and the subsequent T-cell
      mediated immune responses.

PMID- 16651622
TI  - Longitudinal analysis of monocyte/macrophage infection in simian immunodeficiency
      virus-infected, CD8+ T-cell-depleted macaques that develop lentiviral
      encephalitis.
AB  - The histopathological hallmark of lentiviral-associated encephalitis is an
      abundance of infected and activated macrophages. Why a subset of infected hosts
      develops lentiviral encephalitis and others do not is unknown. Using a CD8(+) T
      cell depletion model of simian immunodeficiency virus (SIV)-infected rhesus
      macaques, we examined the relationship between peripheral SIV infection of
      monocytes/macrophages and the development of encephalitis. At the same time that
      cerebral spinal fluid viral load increased in macaques that developed
      encephalitis, we observed that monocyte-derived macrophages from these macaques
      produced more virus than those from macaques that did not develop encephalitis.
      However, during the course of infection, the number of blood monocyte-associated
      SIV DNA copies did not distinguish macaques that developed simian
      immunodeficiency virus encephalitis from macaques that did not develop
      encephalitis. Paradoxically, in this model, macaques that developed encephalitis
      had fewer SIV-infected macrophages in lungs and thymus at postmortem than
      macaques that did not develop encephalitis. These findings suggest that inherent
      differences in host monocyte viral production are related to development of
      encephalitis.

PMID- 16651623
TI  - Uncoupling protein 2 has protective function during experimental autoimmune
      encephalomyelitis.
AB  - Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter
      superfamily that is expressed in many tissues, including immune cells. UCP2
      prevents oxidative stress by reducing reactive oxygen species. Using UCP2
      deficient mice, it was shown that UCP2 is involved in the regulation of insulin
      secretion, in the resistance to infection, and in atherosclerosis. Here, we
      investigated the role of UCP2 in experimental autoimmune encephalomyelitis, a
      murine model of multiple sclerosis. Immunized C57BL/6J UCP2-deficient mice showed
      a slightly delayed onset during experimental autoimmune encephalomyelitis (13.0
      +/- 0.6 versus 11.5 +/- 0.8 in wild-type controls) and developed significantly
      higher disease scores than littermate controls (maximum disease score of 2.9 +/-
      0.2 versus 1.7 +/- 0.2, P = 0.001). Higher levels of infiltrating T cells into
      the spinal cord meninges and parenchyma were observed. The T-cell proliferative
      response to the specific antigen was increased in UCP2-deficient mice compared
      with littermate controls, and CD4 cells of UCP2 knockout mice produced
      significantly higher levels of pro-inflammatory cytokines, eg, tumor necrosis
      factor-alpha and interleukin-2, resulting from a Th1 response. Mice lacking UCP2
      also developed a higher B-cell response. Concomitantly, CD4 and CD8 cells of the
      UCP2-deficient mice showed increased production of reactive oxygen species. These
      results suggest a protective function of UCP2 in chronic inflammatory diseases
      such as multiple sclerosis.

PMID- 16651624
TI  - Inhibition of experimental metastasis by targeting the HUIV26 cryptic epitope in
      collagen.
AB  - Metastasis from the primary tumor to distant sites involves an array of molecules
      that function in an integrated manner. Proteolytic remodeling and subsequent
      tumor cell interactions with the extracellular matrix regulate tumor invasion. In
      previous studies, we have identified a cryptic epitope (HUIV26) that is
      specifically exposed after alterations in the triple helical structure of type IV
      collagen. Exposure of this cryptic epitope plays a fundamental role in the
      regulation of angiogenesis in vivo. However, little is known concerning the
      ability of tumor cells to interact with this cryptic site or whether this site
      regulates tumor cell metastasis in vivo. In this regard, many of the same
      cellular processes that regulate angiogenesis also contribute to tumor
      metastasis. Here we provide evidence that tumor cells such as B16F10 melanoma
      interact with denatured collagen type IV in part by recognizing the HUIV26
      cryptic site. Systemic administration of a HUIV26 monoclonal antibody inhibited
      experimental metastasis of B16F10 melanoma in vivo. Taken together, our findings
      suggest that tumor cell interactions with the HUIV26 cryptic epitope play an
      important role in regulating experimental metastasis and that this cryptic
      element may represent a therapeutic target for controlling the spread of tumor
      cells to distant sites.

PMID- 16651625
TI  - Sequential expression of type IV collagen networks: testis as a model and
      relevance to spermatogenesis.
AB  - The six alpha chains of type IV collagen are organized into three networks:
      alpha1/alpha2, alpha3/alpha4/alpha5, and alpha1/alpha2/alpha5/alpha6. A shift
      from the alpha1/alpha2 to the alpha3/alpha4/alpha5 network occurs in the
      developing glomerular basement membrane, but how the alpha1/alpha2/alpha5/alpha6
      network fits into this sequence is less clear, because the three networks do not
      colocalize. Here, we studied the seminiferous tubule basement membrane of normal
      canine testis where all three networks do colocalize: the alpha1/alpha2 network
      is expressed from birth, the alpha1/alpha2/alpha5/alpha6 network by 5-6 weeks of
      age, and the alpha3/alpha4/alpha5 network by 2 months of age. A canine model of
      Alport syndrome allowed study of the absence of alpha3/alpha4/alpha5 and
      alpha1/alpha2/alpha5/alpha6 networks in testis. In Alport dogs, the seminiferous
      tubule basement membrane was thinner than in controls. Spermatogenesis began at
      the same time as with normal dogs; however, the number of mature sperm was
      significantly reduced in Alport dogs. Thus, it would appear that
      alpha3/alpha4/alpha5 and alpha1/alpha2/alpha5/alpha6 networks are not essential
      for onset of spermatogenesis, but long-term function may be compromised by the
      loss of one or both networks. This situation is analogous to the glomerular
      basement membrane in Alport syndrome. In conclusion, testis can serve as a model
      system to study the sequence of type IV collagen network expression.

PMID- 16651626
TI  - Region-specific dissociation of neuronal loss and neurofibrillary pathology in a
      mouse model of tauopathy.
AB  - Neurofibrillary tangles form in a specific spatial and temporal pattern in
      Alzheimer's disease. Although tangle formation correlates with dementia and
      neuronal loss, it remains unknown whether neurofibrillary pathology causes cell
      death. Recently, a mouse model of tauopathy was developed that reversibly
      expresses human tau with the dementia-associated P301L mutation. This model
      (rTg4510) exhibits progressive behavioral deficits that are ameliorated with
      transgene suppression. Using quantitative analysis of PHF1 immunostaining and
      neuronal counts, we estimated neuron number and accumulation of neurofibrillary
      pathology in five brain regions. Accumulation of PHF1-positive tau in neurons
      appeared between 2.5 and 7 months of age in a region-specific manner and
      increased with age. Neuron loss was dramatic and region-specific in these mice,
      reaching over 80% loss in hippocampal area CA1 and dentate gyrus by 8.5 months.
      We observed regional dissociation of neuronal loss and accumulation of
      neurofibrillary pathology, because there was loss of neurons before
      neurofibrillary lesions appeared in the dentate gyrus and, conversely,
      neurofibrillary pathology appeared without major cell loss in the striatum.
      Finally, suppressing the transgene prevented further neuronal loss without
      removing or preventing additional accumulation of neurofibrillary pathology.
      Together, these results imply that neurofibrillary tangles do not necessarily
      lead to neuronal death.

PMID- 16651627
TI  - Beta-amyloid mediated nitration of manganese superoxide dismutase: implication
      for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse
      model of Alzheimer's disease.
AB  - Alzheimer's disease is a multifactorial, progressive, age-related
      neurodegenerative disease. In familial Alzheimer's disease, Abeta is excessively
      produced and deposited because of mutations in the amyloid precursor protein,
      presenilin-1, and presenilin-2 genes. Here, we generated a double homozygous
      knock-in mouse model that incorporates the Swedish familial Alzheimer's disease
      mutations and converts mouse Abeta to the human sequence in amyloid precursor
      protein and had the P264L familial Alzheimer's disease mutation in presenilin-1.
      We observed Abeta deposition in double knock-in mice beginning at 6 months as
      well as an increase in the levels of insoluble Abeta1-40/1-42. Brain homogenates
      from 3-, 6-, 9-, 12-, and 14-month-old mice showed that protein levels of
      manganese superoxide dismutase (MnSOD) were unchanged in the double knock-in mice
      compared to controls. Genotype-associated increases in nitrotyrosine levels were
      observed. Protein immunoprecipitation revealed MnSOD as a target of this
      nitration. Although the levels of MnSOD protein did not change, MnSOD activity
      and mitochondrial respiration decreased in knock-in mice, suggesting compromised
      mitochondrial function. The compromised activity of MnSOD, a primary antioxidant
      enzyme protecting mitochondria, may explain mitochondrial dysfunction and provide
      the missing link between Abeta-induced oxidative stress and Alzheimer's disease.

PMID- 16651628
TI  - Gangliosides trigger inflammatory responses via TLR4 in brain glia.
AB  - Gangliosides participate in various cellular events of the central nervous system
      and have been closely implicated in many neuronal diseases. However, the precise
      molecular mechanisms underlying the pathological activity of gangliosides are
      poorly understood. Here we report that toll-like receptor 4 (TLR4) may mediate
      the ganglioside-triggered inflammation in glia, brain resident immune cells.
      Gangliosides rapidly altered the cell surface expression of TLR4 in microglia and
      astrocytes within 3 hours. Using TLR4-specific siRNA and a dominant-negative TLR4
      gene, we clearly demonstrate the functional importance of TLR4 in ganglioside
      triggered activation of glia. Inhibition of TLR4 expression by TLR4-siRNA
      suppressed nuclear factor (NF)-kappaB-binding activity, NF-kappaB-dependent
      luciferase activity, and transcription of inflammatory cytokines after exposure
      to gangliosides. Transient transfection of dominant-negative TLR4 also attenuated
      NF-kappaB-binding activity and interleukin-6 promoter activity. In contrast,
      these activities were slightly elevated in cells with wild-type TLR4. In
      addition, CD14 was required for ganglioside-triggered activation of glia, and
      lipid raft formation may be associated with ganglioside-stimulated signal
      propagation. Taken together, these results suggest that TLR4 may provide an
      explanation for the pathological ability of gangliosides to cause inflammatory
      conditions in the brain.

PMID- 16651629
TI  - Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in
      lymphocytes.
AB  - Tyrosine kinases play a fundamental role in cell proliferation, survival,
      adhesion, and motility and have also been shown to mediate malignant cell
      transformation. Here we describe constitutive expression of the protein tyrosine
      kinase Brk in a large proportion of cutaneous T-cell lymphomas and other
      transformed T- and B-cell populations. The kinase is expressed in the nuclear
      localization and activated state. Brk expression was also induced in normal T
      cells on their activation. Introduced expression of the Brk gene resulted in
      markedly diminished cytokine and growth factor dependence of transfected BaF3
      lymphocytes in regard to their in vitro proliferation and survival. Brk also
      conferred in vivo oncogenicity on the BaF3 cells. siRNA-mediated inhibition of
      the endogenous Brk in malignant T cells diminished their growth and survival
      capacity. These findings document inducible expression of Brk in normal T
      lymphocytes and persistent expression of the activated kinase in malignant T and
      B cells. Furthermore, our results indicate that Brk may play a key role in
      lymphomagenesis, hence identifying the kinase as a potential therapeutic target
      in lymphomas.

PMID- 16651630
TI  - The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3
      induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
AB  - Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of
      liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS
      DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the
      development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma
      cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe
      combined immunodeficient mice and exhibited a capillary network morphology that
      was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the
      transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3-
      and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression
      pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by
      accumulation of fat and transformation to a lipoblast-like morphology. In
      conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a
      liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS
      may develop from cell types other than preadipocytes. This may explain the
      preferential occurrence of MLS/RCLS in nonadipose tissues. In addition,
      development of lipoblasts and the typical MLS/RCLS capillary network could be an
      effect of the DDIT3 transcription factor partner of the fusion oncogene.

PMID- 16651631
TI  - Rapid development of salivary gland carcinomas upon conditional expression of K
      ras driven by the cytokeratin 5 promoter.
AB  - We have used a recently described model in which a ras oncogene is expressed in
      cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the
      effects of this oncogene in salivary glands of adult mice. Inducible expression
      of a mutated K-ras gene under the control of the K5 promoter led to the
      development of hyperplastic and dysplastic epithelial lesions and carcinomas,
      with an incidence of 100% and a minimum latency of a week. All major salivary
      glands were affected, as well as a set of previously undescribed buccal accessory
      salivary glands located on the apex of the masseter muscle, close to the oral
      angle. The tumors appear to arise from the cytokeratin 5-positive basal cell
      compartment. Myoepithelial cells participated in the hyperplasias but not in
      carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas
      did not accumulate immunoreactive p53 but are positive for p63, as assayed by
      immunohistochemistry using an antibody against the N terminus of DeltaN p63, a
      splice variant of p63 that can inhibit p53 transcriptional activity. In this
      study, we provide evidence that the ras oncogene, targeted to a specifically
      sensitive cell compartment within the salivary glands, can trigger a series of
      event that are sufficient for full carcinogenesis.

PMID- 16651632
TI  - Galectin-3 expression correlates with apoptosis of tumor-associated lymphocytes
      in human melanoma biopsies.
AB  - The immune system recognizes diverse melanoma antigens. However, tumors can evade
      the immune response, therefore growing and progressing. It has been reported that
      galectin-3 and galectin-1 can induce apoptosis of activated lymphocytes. However,
      there is strong evidence indicating that the regulation of galectins function in
      the human tumor microenvironment is a complex process that is influenced by
      diverse biological circumstances. Here, we have investigated 33 biopsies (eight
      primary and 25 metastases) from 24 melanoma patients (15-72 years old) and
      describe the correlation between the expression of galectin-3 or galectin-1 and
      the level of apoptosis of tumor-associated lymphocytes using immunohistochemistry
      and an in situ nick translation assay. The range of galectin-3-positive tumor
      cells varied between 0% and 93% and that of galectin-1-positive tumor cells
      varied between 5% and 97%. In addition, 23 +/- 27% of tumor-associated
      lymphocytes were apoptotic. Although our results show a correlation between
      galectin-3 expression and apoptosis of tumor-associated lymphocytes, we could not
      find such correlation with galectin-1. Considering the complex process of cancer
      immunoediting, various interacting factors must be considered.

PMID- 16651633
TI  - Osteopontin expression in intratumoral astrocytes marks tumor progression in
      gliomas induced by prenatal exposure to N-ethyl-N-nitrosourea.
AB  - To better study early events in glioma genesis, markers that reliably denote
      landmarks in glioma development are needed. In the present study, we used
      microarray analysis to compare the gene expression patterns of magnetic resonance
      imaging (MRI)-localized N-ethyl-N-nitrosourea (ENU)-induced tumors in rat brains
      with those of uninvolved contralateral side and normal brains. Our analysis
      identified osteopontin (OPN) as the most up-regulated gene in glioma. Using
      immunohistochemistry we then confirmed OPN expression in every tumor examined (n
      = 17), including those with diameters as small as 300 mum. By contrast, no OPN
      immunostaining was seen in normal brain or in brains removed from ENU-exposed
      rats before the development of glioma. Further studies confirmed that OPN was co
      localized exclusively in intratumoral glial fibrillary acidic protein-expressing
      cells and was notably absent from nestin-expressing ones. In conjunction with
      this, we confirmed that both normal neurosphere cells and ENU-im-mortalized
      subventricular zone/striatal cells produced negligible amounts of OPN compared to
      the established rat glioma cell line C6. Furthermore, inducing OPN expression in
      an immortalized cell line increased cell proliferation. Based on these findings,
      we conclude that OPN overexpression in ENU-induced gliomas occurs within a
      specific subset of intratumoral glial fibrillary acidic protein-positive cells
      and becomes evident at the stage of tumor progression.

PMID- 16651634
TI  - Perinatal epidermal growth factor receptor blockade prevents peripheral nerve
      disruption in a mouse model reminiscent of benign world health organization grade
      I neurofibroma.
AB  - Benign peripheral nerve tumors called neurofibromas are a major source of
      morbidity for patients with neurofibromatosis type 1. Some neurofibroma Schwann
      cells aberrantly express the epidermal growth factor receptor (EGFR). In a mouse
      model in which the CNPase promoter drives expression of human EGFR in Schwann
      cells, nerves develop hypertrophy, mast cell accumulation, collagen deposition,
      disruption of axon-glial interactions, characteristics of neurofibroma and are
      hypoalgesic. Administration of the EGFR antagonist cetuximab (IMC-C225) for 2
      weeks beginning at birth in CNPase-hEGFR mice normalized all pathologies at 3
      months of age as evaluated by hotplate testing or histology and by electron
      microscopy. Mast cell chemoattractants brain-derived neurotrophic factor,
      monocyte chemoattractant protein-1, and transforming growth factor-beta1, which
      may account for mast cell accumulation and fibrosis, were reduced by cetuximab.
      Later treatment was much less effective. A birth to 2-week pulse of cetuximab
      blocked hEGFR phosphorylation and Schwann cell prolifera-tion in perinatal mutant
      nerve, so CNPase-hEGFR Schwann cell numbers correlate with the cetuximab effect.
      A >250-fold enlarged population of EGFR(+)/p75(+) cells was detected in newborn
      Nf1(+/-) mouse nerves. These results suggest the existence of an EGFR(+) cell
      enriched in the perinatal period capable of driving complex changes
      characteristic of neurofibroma formation.

PMID- 16651635
TI  - Doxycycline alters vascular smooth muscle cell adhesion, migration, and
      reorganization of fibrillar collagen matrices.
AB  - Remodeling of injured blood vessels is dependent on smooth muscle cells and
      matrix metalloproteinase activity. Doxycycline is a broad spectrum matrix
      metalloproteinase inhibitor that is under investigation for the treatment of
      acute coronary syndromes and aneurysms. In the present study, we examine the
      mechanisms by which doxycycline inhibits smooth muscle cell responses using a
      series of in vitro assays that mimic critical steps in pathological vascular
      remodeling. Doxycycline treatment dramatically increased smooth muscle cell
      adhesion to the substrate, as evidenced by interference reflection microscopy and
      immunostaining for paxillin and phosphotyrosine. Cell aggregation was also
      potentiated after treatment with doxycycline. Treatment with 104 mumol/L
      doxycycline reduced thymidine uptake by 58% compared with untreated cells (P <
      0.05) and inhibited closure of a scrape wound made in a smooth muscle cell
      monolayer by 20% (P < 0.05). Contraction of a three-dimensional collagen gel was
      used as an in vitro model for constrictive vessel remodeling, demonstrating that
      treatment with 416 mumol/L doxycycline for 12 hours inhibited collagen gel
      remodeling by 37% relative to control (P < 0.05). In conclusion, we have shown
      that doxycycline treatment leads to dramatically increased smooth muscle cell
      adhesion, which in turn might limit responses in pathological vascular
      remodeling.

PMID- 16651636
TI  - The origin and in vivo significance of murine and human culture-expanded
      endothelial progenitor cells.
AB  - In adults highly purified populations of early hematopoietic progenitors or cells
      derived from ex vivo expanded unmobilized human peripheral blood mononuclear
      cells contribute to new blood vessel formation. However, the source of these
      culture-expanded endothelial progenitor cells (CE-EPCs) remains controversial. We
      demonstrate that ex vivo expansion of unmobilized human peripheral blood
      generated CE-EPCs with similar numbers, kinetics, and antigen expression profile
      as compared to plating unfractionated CD34(+)/lin(-)-enriched bone marrow
      mononuclear cells. Both CE-EPC populations uniformly co-expressed myeloid and
      endothelial markers, suggesting that peripheral blood progenitor enumeration does
      not correlate with the numbers of early outgrowth CE-EPCs. Using purified myeloid
      subpopulations obtained from mice harboring the lacZ transgene driven by an
      endothelial-specific promoter, we showed that the immature myeloid lineage marker
      CD31(+) cells generated CE-EPCs with fourfold greater frequency than mature
      myeloid populations. Biphenotypic cells co-expressing myeloid/endothelial
      antigens were not detected in circulating human or murine peripheral blood or
      bone marrow but were associated with murine tumors. Unlike CE-EPCs, CD14(+)
      leukocytes admixed within tumors did not generate vWF-positive blood vessels
      during a similarly defined period of tumor growth, but some leukocytes up
      regulated the endothelial marker VE-cadherin. Taken together, the data suggest
      that the local neovascular microenvironment may facilitate vasculogenesis by
      promoting endothelial differentiation and that CE-EPCs may accelerate such
      vasculo-genesis.

PMID- 16651637
TI  - Expression of protein kinase CK2 in astroglial cells of normal and
      neovascularized retina.
AB  - We previously documented protein kinase CK2 involvement in retinal
      neovascularization. Here we describe retinal CK2 expression and combined effects
      of CK2 inhibitors with the somatostatin analog octreotide in a mouse model of
      oxygen-induced retinopathy (OIR). CK2 expression in human and rodent retinas with
      and without retinopathy and in astrocytic and endothelial cultures was examined
      by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase
      chain reaction. A combination of CK2 inhibitors, emodin or 4,5,6,7
      tetrabromobenzotriazole, with octreotide was injected intraperitoneally from
      postnatal (P) day P11 to P17 to block mouse OIR. All CK2 subunits (alpha, alpha',
      beta) were expressed in retina, and a novel CK2alpha splice variant was detected
      by reverse transcriptase-polymerase chain reaction. CK2 antibodies primarily
      reacted with retinal astrocytes, and staining was increased around new
      intraretinal vessels in mouse OIR and rat retinopathy of prematurity, whereas
      preretinal vessels were negative. Cultured astrocytes showed increased
      perinuclear CK2 staining compared to endothelial cells. In the OIR model, CK2
      mRNA expression increased modestly on P13 but not on P17. Octreotide combined
      with emodin or 4,5,6,7-tetrabromobenzotriazole blocked mouse retinal
      neovascularization more efficiently than either compound alone. Based on its
      retinal localization, CK2 may be considered a new immunohistochemical astrocytic
      marker, and combination of CK2 inhibitors and octreotide may be a promising
      future treatment for proliferative retinopathies.

PMID- 16651638
TI  - Activation of mitogen-activated protein kinases by lysophosphatidylcholine
      induced mitochondrial reactive oxygen species generation in endothelial cells.
AB  - Lysophosphatidylcholine (lysoPC) evokes diverse biological responses in vascular
      cells including Ca(2+) mobilization, production of reactive oxygen species, and
      activation of the mitogen-activated protein kinases, but the mechanisms linking
      these events remain unclear. Here, we provide evidence that the response of
      mitochondria to the lysoPC-dependent increase in cytosolic Ca(2+) leads to
      activation of the extracellular signal-regulated kinase (ERK) mitogen-activated
      protein kinase through a redox signaling mechanism in human umbilical vein
      endothelial cells. ERK activation was attenuated by inhibitors of the electron
      transport chain proton pumps (rotenone and antimycin A) and an uncoupler
      (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), suggesting that
      mitochondrial inner membrane potential plays a key role in the signaling pathway.
      ERK activation was also selectively attenuated by chain-breaking antioxidants and
      by vitamin E targeted to mitochondria, suggesting that transduction of the
      mitochondrial hydrogen peroxide signal is mediated by a lipid peroxidation
      product. Inhibition of ERK activation with MEK inhibitors (PD98059 or U0126)
      diminished induction of the antioxidant enzyme heme oxygenase-1. Taken together,
      these data suggest a role for mitochondrially generated reactive oxygen species
      and Ca(2+) in the redox cell signaling path-ways, leading to ERK activation and
      adaptation of the pathological stress mediated by oxidized lipids such as lysoPC.

PMID- 16651639
TI  - Differential regulation of pulmonary endothelial monolayer integrity by varying
      degrees of cyclic stretch.
AB  - Ventilator-induced lung injury is a life-threatening complication of mechanical
      ventilation at high-tidal volumes. Besides activation of proinflammatory cytokine
      production, excessive lung distension directly affects blood-gas barrier and lung
      vascular permeability. To investigate whether restoration of pulmonary
      endothelial cell (EC) monolayer integrity after agonist challenge is dependent on
      the magnitude of applied cyclic stretch (CS) and how these effects are linked to
      differential activation of small GTPases Rac and Rho, pulmonary ECs were
      subjected to physiologically (5% elongation) or pathologically (18% elongation)
      relevant levels of CS. Pathological CS enhanced thrombin-induced gap formation
      and delayed monolayer recovery, whereas physiological CS induced nearly complete
      EC recovery accompanied by peripheral redistribution of focal adhesions and
      cortactin after 50 minutes of thrombin. Consistent with differential effects on
      monolayer integrity, 18% CS enhanced thrombin-induced Rho activation, whereas 5%
      CS promoted Rac activation during the EC recovery phase. Rac inhibition
      dramatically attenuated restoration of monolayer integrity after thrombin
      challenge. Physiological CS preconditioning (5% CS, 24 hours) enhanced EC
      paracellular gap resolution after step-wise increase to 18% CS (30 minutes) and
      thrombin challenge. These results suggest a critical role for the CS amplitude
      and the balance between Rac and Rho in mechanochemical regulation of lung EC
      barrier.

PMID- 16651640
TI  - Apigenin: is it a pro- or anti-inflammatory agent?

PMID- 16651642
TI  - American Society of Clinical Oncology recommendations on fertility preservation
      in cancer patients.
AB  - PURPOSE: To develop guidance to practicing oncologists about available fertility
      preservation methods and related issues in people treated for cancer. METHODS: An
      expert panel and a writing committee were formed. The questions to be addressed
      by the guideline were determined, and a systematic review of the literature from
      1987 to 2005 was performed, and included a search of online databases and
      consultation with content experts. RESULTS: The literature review found many
      cohort studies, case series, and case reports, but relatively few randomized or
      definitive trials examining the success and impact of fertility preservation
      methods in people with cancer. Fertility preservation methods are used
      infrequently in people with cancer. RECOMMENDATIONS: As part of education and
      informed consent before cancer therapy, oncologists should address the
      possibility of infertility with patients treated during their reproductive years
      and be prepared to discuss possible fertility preservation options or refer
      appropriate and interested patients to reproductive specialists. Clinician
      judgment should be employed in the timing of raising this issue, but discussion
      at the earliest possible opportunity is encouraged. Sperm and embryo
      cryopreservation are considered standard practice and are widely available; other
      available fertility preservation methods should be considered investigational and
      be performed in centers with the necessary expertise. CONCLUSION: Fertility
      preservation is often possible in people undergoing treatment for cancer. To
      preserve the full range of options, fertility preservation approaches should be
      considered as early as possible during treatment planning.

PMID- 16651643
TI  - Really, disease doesn't matter? A commentary on correlates of depressive symptoms
      in women treated for early-stage breast cancer.

PMID- 16651644
TI  - Is intravenous arsenic trioxide a useful therapy in myelodysplastic syndromes?

PMID- 16651645
TI  - Predicting vinorelbine disposition and toxicity: does BSA provide more than a
      "bad statistical association"?

PMID- 16651646
TI  - Arsenic trioxide in patients with myelodysplastic syndromes: a phase II
      multicenter study.
AB  - PURPOSE: Evaluation of the safety and efficacy of arsenic trioxide in patients
      with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: MDS patients
      diagnosed according to standard French-American-British criteria received a
      loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a
      maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks.
      Patients were divided into two cohorts: lower-risk MDS (International Prognostic
      Scoring System risk category low or intermediate 1) and higher-risk MDS
      (International Prognostic Scoring System risk category intermediate 2 or high).
      Modified International Working Group criteria were used for response evaluation.
      RESULTS: Of 115 patients enrolled and treated in the study, 67% of patients were
      transfusion dependent at baseline; median age was 68 years. Most treatment
      related adverse events were mild to moderate. The overall rate of hematologic
      improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one
      partial response in the higher-risk cohort. The hematologic response rates were
      13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk
      MDS, respectively. Major responses were observed in all three hematologic
      lineages; 16% of RBC transfusion-dependent patients and 29% of platelet
      transfusion-dependent patients became transfusion independent. At data cut off,
      the median response duration was 3.4 months, with responses ongoing in nine
      patients. CONCLUSION: Arsenic trioxide treatment consisting of an initial loading
      dose followed by maintenance therapy has moderate activity in MDS, inducing
      hematologic responses in both lower- and higher-risk patients. This activity
      combined with a manageable adverse effect profile warrants the additional study
      of arsenic trioxide, particularly in combination therapy, for the treatment of
      patients with MDS.

PMID- 16651647
TI  - Phase II multicenter study of arsenic trioxide in patients with myelodysplastic
      syndromes.
AB  - PURPOSE: To evaluate the efficacy and safety of arsenic trioxide monotherapy in
      patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: Patients
      received arsenic trioxide (0.25 mg/kg/d) on 5 consecutive days per week for 2
      weeks, followed by 2 weeks' rest (one cycle). Two patient cohorts were
      established according to International Prognostic Scoring System risk category:
      lower-risk (low or intermediate-1) or higher-risk MDS (intermediate-2 or high).
      For lower-risk MDS, hematologic improvement (HI) was the primary response end
      point. For higher-risk MDS, additional end points included complete or partial
      remission. Based on the expected time to response, patients receiving two or more
      cycles were prospectively evaluated. RESULTS: Hematologic adverse events included
      neutropenia, thrombocytopenia, and febrile neutropenia. Two patients died during
      the study due to treatment-related toxicities. Most common grade 3/4
      nonhematologic events were pneumonia, fatigue, hemorrhage, pain, and dyspnea.
      Among patients who received one or more doses (n = 70) or completed two or more
      cycles (n = 51), the HI rates were 34% and 39% in lower-risk patients, and 6% and
      9% in higher-risk patients, respectively; the overall major HI rates were 20% and
      22%. One higher-risk patient achieved a complete remission (3%). Major HIs were
      observed in all hematologic lineages; erythroid responses were the most common.
      Transfusion independence or reduction by > or = 50% occurred in 33% of patients
      dependent on RBC transfusions. The overall median duration of HI was 6.8 months
      (range, 2 to 40 months). CONCLUSION: Arsenic trioxide monotherapy has moderate
      activity against MDS, with a manageable adverse effect profile. The further study
      of arsenic trioxide in MDS, particularly in combination with other agents, is
      warranted.

PMID- 16651648
TI  - Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with
      cancer.
AB  - PURPOSE: Marked interindividual variation in drug disposition and toxicity pose
      an ongoing challenge to chemotherapy dosage individualization. The aim of this
      study was to evaluate pretreatment clinical features, genotype and functional
      indicators of drug clearance as predictors of vinorelbine clearance, and
      myelotoxicity that could inform dosage optimization. PATIENTS AND METHODS: Forty
      one patients with cancer received a 60 mg intravenous dose of vinorelbine.
      Pretreatment routine body size measurements and blood tests were performed.
      Midazolam clearance and hepatic technetium labeled sestamibi (99mTc-MIBI)
      clearance were used to investigate CYP3A and ABCB1 (MDR1, P-glycoprotein)
      phenotype respectively and selected single nucleotide polymorphisms in CYP3A and
      ABCB1 were documented. A limited blood sampling strategy was employed and
      vinorelbine concentrations were determined by high-performance liquid
      chromatography. Posterior Bayesian estimates of vinorelbine clearance were
      obtained for each patient using population pharmacokinetic modeling.
      Myelotoxicity was estimated from the fractional survival of neutrophils post
      treatment. RESULTS: There was 4.3-fold variation in vinorelbine clearance across
      the cohort. In a multivariable analysis, pretreatment estimated creatinine
      clearance (P < .01) and hepatic (99m)Tc-MIBI clearance (P = .01) were independent
      predictors of vinorelbine clearance. Fractional survival of neutrophils ranged
      from 1.3% to 100% and was significantly correlated with vinorelbine clearance (P
      < .01). Body-surface area was the only pretreatment predictor of fractional
      survival of neutrophils independent of vinorelbine clearance (P = .02).
      CONCLUSION: Specific indicators of drug clearance provide predictive information
      about vinorelbine pharmacokinetics, and body-surface area, probably reflecting
      normal bone marrow reserve, provides an additional pharmacodynamic indicator. Use
      of a fixed dose of vinorelbine with modifications guided by pretreatment measures
      is worthy of prospective evaluation.

PMID- 16651649
TI  - Objective cancer-related variables are not associated with depressive symptoms in
      women treated for early-stage breast cancer.
AB  - PURPOSE: Women with breast cancer are thought to be vulnerable to depression for
      reasons associated with impact of diagnosis, treatment, and metabolic/endocrine
      changes. While the literature shows that most of these women do not become
      clinically depressed, 15% to 30% report elevated depressive symptoms that may be
      clinically important. The purpose was to identify and determine the relative
      importance of predictors of depressive symptoms in women treated for early-stage
      breast cancer. PATIENTS AND METHODS: A total of 2,595 women (< or = 4 years
      following completion of initial treatment for early-stage breast cancer) provided
      data on cancer-related variables, personal characteristics, health behaviors,
      physical functioning/symptoms, and psychosocial variables. Participants were
      divided into high or low depressive groups using the Center for Epidemiologic
      Studies Depression Scale screening form. RESULTS: Results of the binary logistic
      regression analysis were significant (overall R2 = 32.4%). Before entry of
      psychosocial variables, younger age, being unmarried, poorer physical
      functioning, and more vasomotor and gastrointestinal symptoms were significant
      risk factors for elevated depressive symptoms (R2 = 16.1%), but objective cancer
      related variables were not. After inclusion of psychosocial variables in the
      model (DeltaR2 = 16.3%), none of the preceding variables remained significant.
      Greater risk for depressive symptoms was associated with stressful life events,
      less optimism, ambivalence over expressing negative emotions, sleep disturbance,
      and poorer social functioning. CONCLUSION: Depressive symptoms in women treated
      for early-stage breast cancer are not associated with objective cancer-related
      factors. Rather, they are most strongly linked with many subjective psychosocial
      variables.

PMID- 16651650
TI  - Eukaryotes learn how to count: quorum sensing by yeast.

PMID- 16651651
TI  - Terminating the transcript: breaking up is hard to do.

PMID- 16651652
TI  - Development requires activation but not phosphorylation of beta1 integrins.

PMID- 16651653
TI  - Transcriptional and post-transcriptional regulation of the circadian clock of
      cyanobacteria and Neurospora.
AB  - Circadian clocks are self-sustained oscillators modulating rhythmic transcription
      of large numbers of genes. Clock-controlled gene expression manifests in
      circadian rhythmicity of many physiological and behavioral functions. In
      eukaryotes, expression of core clock components is organized in a network of
      interconnected positive and negative feedback loops. This network is thought to
      constitute the pacemaker that generates circadian rhythmicity. The network of
      interconnected loops is embedded in a supra-net via a large number of interacting
      factors that affect expression and function of core clock components on
      transcriptional and post-transcriptional levels. In particular, phosphorylation
      and dephosphorylation of clock components are critical processes ensuring robust
      self-sustained circadian rhythmicity and entrainment of clocks to external cues.
      In cyanobacteria, three clock proteins have the capacity to generate a self
      sustained circadian rhythm of autophosphorylation and dephosphorylation
      independent of transcription and translation. This phosphorylation rhythm
      regulates the function of these clock components, which then facilitate rhythmic
      gene transcription, including negative feedback on their own genes. In this
      article, we briefly present the mechanism of clock function in cyanobacteria. We
      then discuss in detail the contribution of transcriptional feedback and protein
      phosphorylation to various functional aspects of the circadian clock of
      Neurospora crassa.

PMID- 16651654
TI  - Dynamic regulatory interactions of Polycomb group genes: MEDEA autoregulation is
      required for imprinted gene expression in Arabidopsis.
AB  - The imprinted Arabidopsis Polycomb group (PcG) gene MEDEA (MEA), which is
      homologous to Enhancer of Zeste [E(Z)], is maternally required for normal seed
      development. Here we show that, unlike known mammalian imprinted genes, MEA
      regulates its own imprinted expression: It down-regulates the maternal allele
      around fertilization and maintains the paternal allele silent later during seed
      development. Autorepression of the maternal MEA allele is direct and independent
      of the MEA-FIE (FERTILIZATION-INDEPENDENT ENDOSPERM) PcG complex, which is
      similar to the E(Z)-ESC (Extra sex combs) complex of animals, suggesting a novel
      mechanism. A complex network of cross-regulatory interactions among the other
      known members of the MEA-FIE PcG complex implies distinct functions that are
      dynamically regulated during reproduction.

PMID- 16651655
TI  - Functional coupling of RNAP II transcription to spliceosome assembly.
AB  - The pathway of gene expression in higher eukaryotes involves a highly complex
      network of physical and functional interactions among the different machines
      involved in each step of the pathway. Here we established an efficient in vitro
      system to determine how RNA polymerase II (RNAP II) transcription is functionally
      coupled to pre-mRNA splicing. Strikingly, our data show that nascent pre
      messenger RNA (pre-mRNA) synthesized by RNAP II is immediately and quantitatively
      directed into the spliceosome assembly pathway. In contrast, nascent pre-mRNA
      synthesized by T7 RNA polymerase is quantitatively assembled into the nonspecific
      H complex, which consists of heterogeneous nuclear ribonucleoprotein (hnRNP)
      proteins and is inhibitory for spliceosome assembly. Consequently, RNAP II
      transcription results in a dramatic increase in both the kinetics of splicing and
      overall yield of spliced mRNA relative to that observed for T7 transcription. We
      conclude that RNAP II mediates the functional coupling of transcription to
      splicing by directing the nascent pre-mRNA into spliceosome assembly, thereby
      bypassing interaction of the pre-mRNA with the inhibitory hnRNP proteins.

PMID- 16651656
TI  - A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR
      49-dependent and -independent pathways in C. elegans.
AB  - The Caenorhabditis elegans Nuclear Hormone Receptor NHR-49 coordinates expression
      of fatty acid (FA) metabolic genes during periods of feeding and in response to
      fasting. Here we report the identification of MDT-15, a subunit of the C. elegans
      Mediator complex, as an NHR-49-interacting protein and transcriptional
      coactivator. Knockdown of mdt-15 by RNA interference (RNAi) prevented fasting
      induced mRNA accumulation of NHR-49 targets in vivo, and fasting-independent
      expression of other NHR-49 target genes, including two FA-Delta9-desaturases (fat
      5, fat-7). Interestingly, mdt-15 RNAi affected additional FA-metabolism genes
      (including the third FA-Delta9-desaturase, fat-6) that are regulated
      independently of NHR-49, suggesting that distinct unidentified regulatory factors
      also recruit MDT-15 to selectively modulate metabolic gene expression. The
      deregulation of FA-Delta9-desaturases by knockdown of mdt-15 correlated with
      dramatically decreased levels of unsaturated FAs and multiple deleterious
      phenotypes (short life span, sterility, uncoordinated locomotion, and
      morphological defects). Importantly, dietary addition of specific polyunsaturated
      FAs partially suppressed these pleiotropic phenotypes. Thus, failure to properly
      govern FA-Delta9-desaturation contributed to decreased nematode viability. Our
      findings imply that a single subunit of the Mediator complex, MDT-15, integrates
      the activities of several distinct regulatory factors to coordinate metabolic and
      hormonal regulation of FA metabolism.

PMID- 16651657
TI  - A mitotic topoisomerase II checkpoint in budding yeast is required for genome
      stability but acts independently of Pds1/securin.
AB  - Topoisomerase II (Topo II) performs topological modifications on double-stranded
      DNA molecules that are essential for chromosome condensation, resolution, and
      segregation. In mammals, G2 and metaphase cell cycle delays induced by Topo II
      poisons have been proposed to be the result of checkpoint activation in response
      to the catenation state of DNA. However, the apparent lack of such controls in
      model organisms has excluded genetic proof that Topo II checkpoints exist and are
      separable from the conventional DNA damage checkpoint controls. But here, we
      define a Topo II-dependent G2/M checkpoint in a genetically amenable eukaryote,
      budding yeast, and demonstrate that this checkpoint enhances cell survival.
      Conversely, a lack of the checkpoint results in aneuploidy. Neither DNA damage
      responsive pathways nor Pds1/securin are needed for this checkpoint. Unusually,
      spindle assembly checkpoint components are required for the Topo II checkpoint,
      but checkpoint activation is not the result of failed chromosome biorientation or
      a lack of spindle tension. Thus, compromised Topo II function activates a yeast
      checkpoint system that operates by a novel mechanism.

PMID- 16651658
TI  - Monocytic leukemia zinc finger protein is essential for the development of long
      term reconstituting hematopoietic stem cells.
AB  - Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and
      member of the MYST family of histone acetyltransferases, is the target of
      recurrent translocations in acute myeloid leukemia. Since genes associated with
      translocations in leukemia are typically important regulators of blood formation,
      we investigated if Moz has a role in normal hematopoiesis. We generated mice
      carrying a mutation in the Moz gene. Homozygous Moz mutant mice died at birth.
      Moz mutant fetal liver hematopoietic cells were incapable of contributing to the
      hematopoietic system of recipients after transplantation. We observed profound
      defects in the stem cell compartment of Moz-deficient mice. Progenitors of all
      lineages were reduced in number. However, blood cell lineage commitment was
      unaffected. Together, these results show that Moz is essential for a fundamental
      property of hematopoietic stem cells, the ability to reconstitute the
      hematopoietic system of a recipient after transplantation and that Moz is
      specifically required in the stem cell compartment.

PMID- 16651659
TI  - SOX2 is a dose-dependent regulator of retinal neural progenitor competence.
AB  - Approximately 10% of humans with anophthalmia (absent eye) or severe
      microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, a
      SOXB1-HMG box transcription factor. However, at present, the molecular or
      cellular mechanisms responsible for these conditions are poorly understood. Here,
      we directly assessed the requirement for SOX2 during eye development by
      generating a gene-dosage allelic series of Sox2 mutations in the mouse. The Sox2
      mutant mice display a range of eye phenotypes consistent with human syndromes and
      the severity of these phenotypes directly relates to the levels of SOX2
      expression found in progenitor cells of the neural retina. Retinal progenitor
      cells with conditionally ablated Sox2 lose competence to both proliferate and
      terminally differentiate. In contrast, in Sox2 hypomorphic/null mice, a reduction
      of SOX2 expression to <40% of normal causes variable microphthalmia as a result
      of aberrant neural progenitor differentiation. Furthermore, we provide genetic
      and molecular evidence that SOX2 activity, in a concentration-dependent manner,
      plays a key role in the regulation of the NOTCH1 signaling pathway in retinal
      progenitor cells. Collectively, these results show that precise regulation of
      SOX2 dosage is critical for temporal and spatial regulation of retinal progenitor
      cell differentiation and provide a cellular and molecular model for understanding
      how hypomorphic levels of SOX2 cause retinal defects in humans.

PMID- 16651660
TI  - The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal
      sterols.
AB  - Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7)
      that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the
      origin of fetal sterols. Because their heterozygous mothers synthesize
      cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus
      having a Delta(7) or a Delta(8) double bond must have been synthesized by the
      fetus itself but any cholesterol had to have come from the mother. Early in
      gestation, most fetal sterols were of maternal origin, but at approximately E13
      14, in situ synthesis became increasingly important, and by birth, 55-60% of
      liver and lung sterols had been made by the fetus. In contrast, at E10-11, upon
      formation of the blood-brain barrier, the brain rapidly became the source of
      almost all of its own sterols (90% at birth). New, rapid, de novo sterol
      synthesis in brain was confirmed by the observation that concentrations of C24,25
      unsaturated sterols were low in the brains of all very young fetuses but
      increased rapidly beginning at approximately E11-12. Reduced activity of sterol
      C24,25-reductase (Dhcr24) in brain, suggested by the abundance of C24,25
      unsaturated compounds, seems to be the result of suppressed Dhcr24 expression.
      The early fetal brain also appears to conserve cholesterol by keeping cholesterol
      24-hydroxylase expression low until approximately E18.

PMID- 16651661
TI  - Regulation of de novo phosphatidylinositol synthesis.
AB  - Mechanisms that function to regulate the rate of de novo phosphatidylinositol
      (PtdIns) synthesis in mammalian cells have not been elucidated. In this study, we
      characterize the effect of phorbol ester treatment on de novo PtdIns synthesis in
      C3A human hepatoma cells. Incubation of cells with 12-O-tetradecanoyl phorbol 13
      acetate (TPA) initially (1-6 h) results in a decrease in precursor incorporation
      into PtdIns; however, at later times (18-24 h), a marked increase is observed.
      TPA-induced glucose uptake from the medium is not required for observation of the
      stimulation of PtdIns synthesis, because the effect is apparent in glucose-free
      medium. Inhibition of the activation of arachidonic acid substantially blocks the
      synthesis of PtdIns but has no effect on the synthesis of phosphatidylcholine
      (PtdCho). Increasing the concentration of cellular phosphatidic acid by blocking
      its conversion to diacylglycerol, on the other hand, enhances the synthesis of
      PtdIns and inhibits the synthesis of PtdCho. The TPA-induced stimulation of
      PtdIns synthesis is not the result of the concomitant TPA-induced G1 arrest,
      because G1 arrest induced by mevastatin has no effect on PtdIns synthesis.
      Inhibition of protein kinase C activity blocks the stimulatory action of TPA on
      de novo synthesis of PtdIns but has no effect on TPA-induced inhibition.
      Potential sites of enzymatic regulation are discussed.

PMID- 16651662
TI  - Embracing the complexity of genomic data for personalized medicine.
AB  - Numerous recent studies have demonstrated the use of genomic data, particularly
      gene expression signatures, as clinical prognostic factors in cancer and other
      complex diseases. Such studies herald the future of genomic medicine and the
      opportunity for personalized prognosis in a variety of clinical contexts that
      utilizes genome-scale molecular information. The scale, complexity, and
      information content of high-throughput gene expression data, as one example of
      complex genomic information, is often under-appreciated as many analyses continue
      to focus on defining individual rather than multiplex biomarkers for patient
      stratification. Indeed, this complexity of genomic data is often--rather
      paradoxically--viewed as a barrier to its utility. To the contrary, the
      complexity and scale of global genomic data, as representing the many dimensions
      of biology, must be embraced for the development of more precise clinical
      prognostics. The need is for integrated analyses--approaches that embrace the
      complexity of genomic data, including multiple forms of genomic data, and aim to
      explore and understand multiple, interacting, and potentially conflicting
      predictors of risk, rather than continuing on the current and traditional path
      that oversimplifies and ignores the information content in the complexity. All
      forms of potentially relevant data should be examined, with particular emphasis
      on understanding the interactions, complementarities, and possible conflicts
      among gene expression, genetic, and clinical markers of risk.

PMID- 16651663
TI  - A genome-wide distribution of 8-oxoguanine correlates with the preferred regions
      for recombination and single nucleotide polymorphism in the human genome.
AB  - 8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is
      considered to be a natural cause of genomic diversity in organisms because of its
      mutagenic potential. The steady-state level of 8-oxoG in the nuclear genome of a
      human cell has been estimated to be several residues per 10(6) guanines. In the
      present study, to clarify the genome-wide distribution of 8-oxoG in the steady
      state, we performed fluorescence in situ detection of 8-oxoG on human metaphase
      chromosomes using a monoclonal antibody. Multiple dot-like signals were observed
      on each metaphase chromosome. We then mapped the position of the signal at
      megabase resolution referring to the cytogenetically identified chromosomal band,
      and demonstrated that 8-oxoG is unevenly distributed in the normal human genome
      and that the distribution pattern is conserved among different individuals.
      Moreover, we found that regions with a high frequency of recombination and single
      nucleotide polymorphisms (SNPs) are preferentially located within chromosomal
      regions with a high density of 8-oxoG. Our findings suggest that 8-oxoG is one of
      the main causes of frequent recombinations and SNPs in the human genome, which
      largely contribute to the genomic diversity in human beings.

PMID- 16651664
TI  - The fate of laterally transferred genes: life in the fast lane to adaptation or
      death.
AB  - Large-scale genome arrangement plays an important role in bacterial genome
      evolution. A substantial number of genes can be inserted into, deleted from, or
      rearranged within genomes during evolution. Detecting or inferring gene
      insertions/deletions is of interest because such information provides insights
      into bacterial genome evolution and speciation. However, efficient inference of
      genome events is difficult because genome comparisons alone do not generally
      supply enough information to distinguish insertions, deletions, and other
      rearrangements. In this study, homologous genes from the complete genomes of 13
      closely related bacteria were examined. The presence or absence of genes from
      each genome was cataloged, and a maximum likelihood method was used to infer
      insertion/deletion rates according to the phylogenetic history of the taxa. It
      was found that whole gene insertions/deletions in genomes occur at rates
      comparable to or greater than the rate of nucleotide substitution and that higher
      insertion/deletion rates are often inferred to be present at the tips of the
      phylogeny with lower rates on more ancient interior branches. Recently
      transferred genes are under faster and relaxed evolution compared with more
      ancient genes. Together, this implies that many of the lineage-specific
      insertions are lost quickly during evolution and that perhaps a few of the genes
      inserted by lateral transfer are niche specific.

PMID- 16651665
TI  - Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli
      global regulation.
AB  - The role of nonlinear DNA in replication, recombination, and transcription has
      become evident in recent years. Although several studies have predicted and
      characterized regulatory elements at the sequence level, very few have
      investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4
      DNA motifs as a model, we have researched the role of DNA structure in
      transcription on a genome-wide scale. Analyses of >61,000 open reading frames
      (ORFs) across 18 prokaryotes show enrichment of G4 motifs in regulatory regions
      and indicate its predominance within promoters of genes pertaining to
      transcription, secondary metabolite biosynthesis, and signal transduction. Based
      on this, we predict that G4 DNA may present regulatory signals. This is supported
      by conserved G4 motifs in promoters of orthologous genes across phylogenetically
      distant organisms. We hypothesized a regulatory role of G4 DNA during
      supercoiling stress, when duplex destabilization may result in G4 formation. This
      is in line with our observations from target site analysis for 55 DNA-binding
      proteins in Escherichia coli, which reveals significant (P<0.001) association of
      G4 motifs with target sites of global regulators FIS and Lrp and the sigma factor
      RpoD (sigma70). These factors together control >1000 genes in the early growth
      phase and are believed to be induced by supercoiled DNA. We also predict G4 motif
      induced supercoiling sensitivity for >30 operons in E. coli, and our findings
      implicate G4 DNA in DNA-topology-mediated global gene regulation in E. coli.

PMID- 16651666
TI  - Iterative gene prediction and pseudogene removal improves genome annotation.
AB  - Correct gene prediction is impaired by the presence of processed pseudogenes:
      nonfunctional, intronless copies of real genes found elsewhere in the genome.
      Gene prediction programs frequently mistake processed pseudogenes for real genes
      or exons, leading to biologically irrelevant gene predictions. While methods
      exist to identify processed pseudogenes in genomes, no attempt has been made to
      integrate pseudogene removal with gene prediction, or even to provide a
      freestanding tool that identifies such erroneous gene predictions. We have
      created PPFINDER (for Processed Pseudogene finder), a program that integrates
      several methods of processed pseudogene finding in mammalian gene annotations. We
      used PPFINDER to remove pseudogenes from N-SCAN gene predictions, and show that
      gene prediction improves substantially when gene prediction and pseudogene
      masking are interleaved. In addition, we used PPFINDER with gene predictions as a
      parent database, eliminating the need for libraries of known genes. This allows
      us to run the gene prediction/PPFINDER procedure on newly sequenced genomes for
      which few genes are known.

PMID- 16651667
TI  - Painless procedures in pediatrics pipe dream or a possibility.

PMID- 16651668
TI  - Juvenile hyperthyroidism: an experience.
AB  - OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at
      presentation, their treatment outcome; predictors of remission and relapse.
      METHODS: Retrospective analysis of medical records of 56 patients with juvenile
      hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18
      males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was
      analyzed. RESULTS: Majority of patients was in the age group of 12-16 years.
      Common symptoms observed at presentation were weight loss (82.1%), excessive
      sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and
      diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of
      patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and
      4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6),
      T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5
      microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated
      with carbimazole; subsequently 4 patients required thyroidectomy and one required
      radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients
      was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of
      treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD)
      duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33
      months. On intention to treat analysis, remission with carbimazole was achieved
      in 47.6%, remaining patients failed to achieve remission with drug treatment.
      CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism.
      Carbimazole is safe, effective, cheap, and easily available form of therapy. It
      is occasionally associated with serious side effects but requires prolonged
      follow up.

PMID- 16651669
TI  - Safe and efficacious use of procedural sedation and analgesia by non
      anesthesiologists in a pediatric hematology-oncology unit.
AB  - BACKGROUND: Children often require relief of pain and anxiety while undergoing
      diagnostic and therapeutic procedures. Procedural sedation and analgesia (PSA) is
      the safe and effective control of pain, anxiety and motion so as to allow a
      necessary procedure to be performed and to provide an appropriate degree of
      memory loss or decreased awareness. OBJECTIVE: To prospectively describe
      procedural sedation and analgesia as performed in the pediatric oncology unit and
      to report the success of sedation and the incidence of complications. METHODS: IV
      Midazolam and IV Ketamine were used for PSA in pediatric oncology patients
      undergoing painful procedures. RESULTS: Between June 2004 and December 2004, 55
      diagnostic and therapeutic procedures were performed using PSA in 16 children.
      There were 9 boys and 7 girls with a median age of 11 years. Twelve patients had
      hematolymphoid malignancies and 4 patients had solid tumors. The indication for
      PSA were bone marrow aspiration and or biopsy in 7 patients, therapeutic lumbar
      puncture in 43 patients, bone marrow aspiration and lumbar puncture in 4 patients
      and skin biopsy in 1 patient. All 55 procedures were successfully completed.
      Adverse events occurred in 15 (27%) episodes and included transient drop in
      oxygen saturation, vomiting, dizziness and disinhibition with crying spells.
      Average time to arousable state and full recovery was 22 minutes and 31 minutes
      respectively. None of the patients complained of post procedure pain nor recalled
      the procedure at the follow up visit. CONCLUSION: Procedural sedation and
      analgesia using midazolam and ketamine is a safe and efficient method of limiting
      anxiety and procedure related pain and can be successfully administered by non
      anaesthesiologists. The complication rate is low and can be easily managed.

PMID- 16651670
TI  - Avian flu and possible human pandemic.
AB  - Avian flu is affecting the poultry animals world over since first outbreak in
      1997 in Hong Kong and has resulted in 92 human deaths and culling of more than
      150 million poultry animals in Asia and Europe. The loss to the economy has also
      been enormous. 13 new countries, including India, reported occurrence of the
      disease in poultry animals in February 2006 only, to the World Health
      Organisation. This rapid rate of spread of virus along with notoriety of the
      virus for frequent genetic re-assortment, which might enable H5N1 to infect human
      beings, threatens of possible influenza pandemic since the last pandemic in 1968.
      The human influenza caused by this subtype of the virus (H5N1) has high case
      fatality of 54% and majority of affected humans are between the age of 5 to 23
      years. Lack of effective vaccine, poor knowledge about treatment, and with
      scarcity of public health measures in developing countries are major causes of
      concern. The real threat of impending pandemic can be avoided only if we act
      immediately on the basis of currently available source of information and apply
      scientific knowledge rationally for containment and prevention of bird flu and
      treat human cases promptly.

PMID- 16651671
TI  - Childhood hypertension.

PMID- 16651672
TI  - A reappraisal of the criteria to diagnose plasma leakage in dengue hemorrhagic
      fever.
AB  - A study was undertaken to analyze the usefulness of radiographic and
      ultrasonographic findings and area specific hematocrit cut off values in Dengue
      Hemorrhagic Fever (DHF). Of the 65 cases, 35 were DHF and 30 were Dengue Fever as
      per the WHO case definition. Among the DHF cases, hemoconcentration (>20%) was
      detected in 20 cases (57.14%), hypoproteinemia in 11 (31.42%) and clinical
      evidence of pleural effusion and or ascites in 25 (71.42%). Hemoconcentration
      based on area specific hematocrit cut off values was observed in 32 cases
      (91.42%). Ultrasonographic evidence of plasma leakage was seen in 32 cases
      (91.42%). In detecting plasma leakage, area specific hematocrit cut off values
      and ultrasonography had the highest sensitivity (91.42%), while ultrasonography
      had the highest negative predictive value of 84.21%. Clinical evidence of plasma
      leakage was more frequent than hemoconcentration or hypoproteinuria.
      Ultrasonography is an ideal non-invasive investigation to detect plasma leakage
      and area specific hematocrit values are useful as evidence of plasma leakage.

PMID- 16651673
TI  - Attenuated form of Evans syndrome among pediatric ITP patients.
AB  - Long term follow up of adult patients with immune thrombocytopenic purpura (ITP)
      have shown evolvement of secondary autoimmune diseases such as SLE, Evans
      syndrome, autoimmune neutropenia, Graves disease etc. We studied 30 cases of
      pediatric ITP patients for evidence of hemolysis to assess the possibility of
      Evans like syndrome. Measurement of free serum haptoglobin, a sensitive indicator
      of red cell destruction was used after careful exclusion of micro angiopathic
      hemolysis, SLE or overt Evans Syndrome. Results showed abnormally low level of
      free serum haptoglobin in 11 of the 30 (36.7%) patients compared to that in 20
      age matched controls (P < 0.001) as an evidence of hemolysis. Our data in
      pediatric patients is similar to that reported in adult ITP cases and support the
      observation of Evans made 50 years ago that there is a spectrum like relationship
      between primary thrombocytopenia and hemolytic anemia. Thus the concept of
      attenuated form of Evans syndrome could be considered, in group of patients with
      ITP in pediatric age group.

PMID- 16651674
TI  - Profile of neonates admitted in pediatric ICU and validation of Score for
      Neonatal Acute Physiology (SNAP).
AB  - A retrospective study was conducted in the Pediatric Intensive Care Unit (PICU)
      of a tertiary care hospital in northern India to profile neonatal admissions and
      to assess the validity of the Score for Neonatal Acute Physiology (SNAP) in
      predicting the outcome in terms of mortality and length of hospital stay (LOS).
      Neonatal sepsis (51%) and birth asphyxia (11.2%) were the commonest indications
      for admission. Thirty-seven (38.1%) of the neonates died. The mean SNAP score in
      babies who died was 18.8 +/- 9.8 and 10.1 +/- 6.4 in survivors (P<0.001). There
      was no correlation between SNAP score and mean length of stay in hospital
      (P=0.5). We conclude that SNAP correlates well with mortality in neonates
      admitted to the PICU.

PMID- 16651675
TI  - Proximal femoral focal deficiency.

PMID- 16651676
TI  - Herpes zoster with dissemination.
AB  - Herpes zoster or shingles is an acute vesico-bullous cutaneous infection
      characterized by dermatomal distribution, predominantly in adults. Extensive
      cutaneous dissemination has been reported in immunocompromised patients. However,
      its existence is documented in immunocompetent individuals as well. We report two
      children with disseminated herpes zoster, one of whom was immunocompromised
      secondary to severe mal-nutrition and had associated orbital septal cellulitis.

PMID- 16651677
TI  - Constitutional tetrasomy 18p.
AB  - We present here the first case of constitutional tetrasomy 18p from India. A 3
      year old female with developmental delay and dysmorphic features revealed
      47,XX,+mar karyotype. The small meta-centric marker chromosome was identified as
      i(18p) with m-FISH followed by m-BAND. Parents and a normal sibling of the
      proband revealed normal karyotype. There was history of mental retardation and
      dysmorphic features in four cases on paternal side; however, their karyotype was
      also normal.

PMID- 16651678
TI  - Subcutaneous fat necrosis with hypercalcemia.
AB  - Subcutaneous fat necrosis of the newborn (SCFN) is an uncommon condition and may
      be complicated by hypercalcemia. A 28-day-old neonate, presenting with SCFN,
      hypercalcemia and nephrocalcinosis was managed with intravenous saline followed
      by furosemide, oral prednisolone, potassium citrate and etidronate.

PMID- 16651679
TI  - Scimitar syndrome.

PMID- 16651680
TI  - Acute transverse myelitis following hepatitis E virus infection.

PMID- 16651681
TI  - Errors in administration of combination antibiotics.

PMID- 16651682
TI  - How baby friendly are the baby products?

PMID- 16651683
TI  - Repeated cutdown intervention in cutis marmorata telengiectatica.

PMID- 16651684
TI  - Avoidance of food allergens in asthma (reply).

PMID- 16651685
TI  - More steps needed to tackle authors who do not respond.

PMID- 16651686
TI  - Abscess of the nasal septum with staphylococcal scalded skin syndrome.

PMID- 16651687
TI  - Prognostic value of early vs late steroid resistance in idiopathic nephrotic
      syndrome.

PMID- 16651689
TI  - Effects of dietary genistein on nutrient use and mineral status in heat-stressed
      quails.
AB  - Genistein is a powerful antioxidant and plays a role in calcium and bone
      metabolism. We evaluated the efficacy of dietary supplementation with genistein
      on the nutrient use and mineral concentrations in tibia and serum of quails
      reared at high environmental temperature (34 degrees C). Two hundred and forty
      Japanese quails (10 days old) were randomly assigned to 8 treatment groups
      consisting of 10 replicates of 3 birds. The birds were kept in a temperature
      controlled room at 22 degrees C (Thermoneutral, TN groups) or 34 degrees C (for 8
      h/d; 09.00 am-05.00 pm; Heat stress, HS groups). Birds were fed either a basal
      diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of
      genistein/kg of diet. Heat exposure decreased apparent nutrient digestibility and
      bone mineralization when the basal diet was fed (P < 0.001). Apparent
      digestibility of dry matter (DM) (P < 0.05), crude protein (CP) (P < 0.05) and
      ash (P < 0.01) was significantly improved by genistein supplementation. However,
      this improvement was not in direct proportion to increased doses of supplement
      since there was no difference when diets included either 400 or 800 mg
      genistein/kg of diet (P < 0.05) in birds reared under heat stress. The amounts of
      Ca, P, Mg, Mn, Zn, Fe and Cu in the excreta decreased (P < 0.01), while Ca, P,
      Mg, Mn, Zn and Cu concentrations in tibia ash increased in quails reared under
      heat stress conditions (P < 0.01) with genistein supplementation. Ca and P
      concentrations in tibia ash were also increased in birds kept under thermoneutral
      conditions with genistein supplementation. Increased serum alkaline phosphatase
      activity (P < 0.01) was associated with increasing dietary genistein in all
      groups. In conclusion, genistein supplementation to the basal diet improved
      digestibility of CP, DM and ash and levels of Ca and P and bone mineralization in
      quails reared under heat stress conditions.

PMID- 16651690
TI  - Study on the ophthalmic diseases in ICR mice and BALB/c mice.
AB  - In pharmaceutical companies and research institutes, many toxicity tests are
      performed with laboratory animals. This study was performed to produce reference
      data for eye toxicity tests and to investigate the ophthalmic diseases of 408 ICR
      mice and 119 BALB/c mice, which are commonly used as subjects in toxicity tests.
      The experimental animals without clinical disorders were selected regardless of
      sex. The ophthalmic diseases were examined by using special ophthalmic
      instruments: direct ophthalmoscope, indirect ophthalmoscope, slit-lamp
      biomicroscope and focal illuminator. The most prevalent ocular variation within
      normal limits was hyaloid vessel remnant (ICR mice, 28.2%; BALB/c mice, 31.9%)
      and the incidence gradually decreased with age. The ocular diseases found in ICR
      mice were retinal degeneration (9.8%), corneal scar (4.2%), focal cataract
      (2.2%), anisocoria (1.2%), corneal ulcer (0.2%) and uveitis (0.2%). In BALB/c
      mice, corneal scar (9.2%), focal cataract (1.7%) and corneal ulcer (0.8%) were
      the ocular diseases found.

PMID- 16651691
TI  - Quantitative trait loci determining weight reduction of testes and pituitary by
      diethylstilbesterol in LEXF and FXLE recombinant inbred strain rats.
AB  - Increasing exposure to environmental endocrine disruptor, xeno-estrogen, is a
      serious hazard to male reproductive activity. To explore possible genetic control
      in susceptibility to xeno-estrogen, the weight reduction of testes induced by the
      continuous administration of a synthetic estrogen, diethylstilbesterol, were
      investigated by quantitative trait analysis in LEXF and FXLE recombinant inbred
      strain rats, consisting of 21 independent strains, 9 of their substrains,
      parental F344/Stm and LE/Stm strains, and (F344 x LE)F1. For the weight of
      testes, one highly significant quantitative trait locus (QTL) and one significant
      QTL were mapped on chromosomes 7 and 1, respectively. The QTL on chromosome 7 is
      closely associated with c-myc. Pituitary weight and serum prolactin were also
      variable among recombinant inbred strains, but no QTL was detected for them in
      this study.

PMID- 16651692
TI  - Detection of quantitative trait loci causing abnormal spermatogenesis and reduced
      testis weight in the small testis (Smt) mutant mouse.
AB  - The small testis (Smt) mutant mouse is characterized by a small testis of one
      third to one half the size of a normal testis, and its spermatogenesis is mostly
      arrested at early stages of meiosis, although a small number of spermatocytes at
      the late prophase of meiosis and a few spermatids can sometimes be seen. We
      performed quantitative trait locus (QTL) analysis of these spermatogenic traits
      and testis weight using 221 F2 males obtained from a cross between Smt and MOM
      (Mus musculus molossinus) mice. At the genome-wide 5% level, we detected two QTLs
      affecting meiosis on chromosomes 4 and 13, and two QTLs for paired testis weight
      as a percentage of body weight on chromosomes 4 and X. In addition, we found
      several QTLs for degenerated germ cells and multinuclear giant cells on
      chromosomes 4, 7 and 13. Interestingly, for cell degeneration, the QTL on
      chromosome 13 interacted epistatically with the QTL on chromosome 4. These
      results reveal polygenic participation in the abnormal spermatogenesis and small
      testis size in the Smt mutant.

PMID- 16651693
TI  - Type 2 diabetes mellitus in obese mouse model induced by monosodium glutamate.
AB  - The number of diabetic patients is increasing every year, and new model animals
      are required to study the diverse aspects of this disease. An experimental obese
      animal model has reportedly been obtained by injecting monosodium glutamate (MSG)
      to a mouse. We found that ICR-MSG mice on which the same method was used
      developed glycosuria. Both female and male mice were observed to be obese but had
      no polyphagia, and were glycosuric by 29 weeks of age, with males having an
      especially high rate of incidence (70.0%). Their blood concentrations of glucose,
      insulin, total cholesterol, and triglycerides were higher than in the control
      mice at 29 weeks. These high concentrations appeared in younger males more often
      than in females, and were severe in adult males. Also, the mice at 54 weeks of
      age showed obvious obesity and increased concentrations of glucose, insulin, and
      total cholesterol in the blood. The pathological study of ICR-MSG female and male
      mice at 29 weeks of age showed hypertrophy of the pancreatic islet. This was also
      observed in most of these mice at 54 weeks. It was recognized as a continuation
      of the condition of diabetes mellitus. From the above results, these mice are
      considered to be useful as new experimental model animals developing a high rate
      of obese type 2 (non-insulin dependent) diabetes mellitus without polyphagia.

PMID- 16651694
TI  - Development of ELISA using recombinant antigens for specific detection of mouse
      parvovirus infection.
AB  - Nucleotide sequences of mouse parvovirus (MPV) isolate, named MPV/UT, and mouse
      minute virus (MMV) were analyzed and used for expressing recombinant proteins in
      E. coli. ELISA tests using recombinant major capsid protein (rVP2) and
      recombinant major non-structural protein (rNS1) as antigens were developed and
      their performance in serologic detection of rodent parvovirus infection was
      assessed. MPV-rVP2 and MMV-rVP2 ELISAs reacted specifically with anti-MPV and
      anti-MMV mouse sera, respectively. MMV-rNS1 antigen had a wide reaction range
      with antisera to rodent parvoviruses including MPV, MMV, Kilham rat virus (KRV)
      and H-1 virus. All mice oronasally infected with MPV were seropositive at 4 weeks
      post-infection in screening by ELISAs using MPV-rVP2 and MMV-rNS1 antigens, but
      were negative by conventional ELISA using whole MMV antigen. A contact
      transmission experiment revealed that transmission of MPV occurred up to 4 weeks
      post-infection, and all cage mates were seropositive in screening with MPV-rVP2
      and MMV-rNS1 ELISAs. These results indicate that MPV-rVP2 and MMV-rVP2 are
      specific ELISA antigens which distinguish between MPV and MVM infection, while
      MMV-rNS1 antigen can be used in generic ELISA for a variety of rodent
      parvoviruses. The higher sensitivity of MPV-rVP2 ELISA than conventional ELISA
      for detecting seroconversion to MPV in oronasally infected mice as well as in
      cage mates suggests the usefulness of MPV-rVP2 ELISA in quarantine and
      microbiological monitoring of MPV infection in laboratory mice.

PMID- 16651695
TI  - Ultrasonic vocalization response elicited in adjuvant-induced arthritic rats as a
      useful method for evaluating analgesic drugs.
AB  - Adjuvant-induced arthritic (AIA) rats develop a severe chronic polyarthritis
      which shares some features in common with human rheumatoid arthritis. The purpose
      of the present study was to examine whether AIA rats emit ultrasonic
      vocalizations (USVs) when they are confronted with a healthy 'stimulus rat' in
      social interactions. We also examined the effects of three analgesic drugs
      (piroxicam, rofecoxib and ketoprofen) on USV responses using the same paradigm.
      In social interactions, AIA rats and intact controls emitted USVs in the 22-28
      kHz range. Vocalization activities were significantly higher in AIA rats than
      those in intact controls. Moreover, the USVs of AIA rats were significantly
      inhibited by the three analgesic drugs. These results suggest that the USV
      responses elicited in AIA rats are useful for the evaluation of analgesic drugs.

PMID- 16651696
TI  - No effect of recombinase-mediated DNA transfer on production efficiency of
      transgenic rats.
AB  - It was reported that recombinase-A protein (RecA)-coated exogenous DNA was more
      likely to be integrated into mouse, goat and pig genomes. The objective of this
      study was to investigate whether integration of exogenous DNA into the rat genome
      is improved by the recombinase-mediated DNA transfer. Pronuclear microinjection
      of RecA-coated EGFP or OAMB DNA resulted in a production efficiency of transgenic
      rats of 1.4-2.9%, comparable with 0.9-2.6% when non-coated control DNA was used.
      Intracytoplasmic injection of the sperm heads exposed to RecA-coated EGFP DNA did
      not produce any transgenic rats (0 vs. 0-2.8% in control groups). Thus, the
      recombinase-mediated DNA transfer contributed very little to the production of
      transgenic rats by means of pronuclear microinjection and intracytoplasmic sperm
      injection.

PMID- 16651697
TI  - High-efficiency CAG-FLPe deleter mice in C57BL/6J background.
AB  - The increasing popularity of conditional knockout (KO) technology has resulted in
      the demand for efficient FLP deleter mice. In addition, FLP deleters are needed
      in genetic backgrounds that are suited to behavioral studies. We generated CAG
      FLPe transgenic (Tg) mice with the C57BL/6J genetic background, which is one of
      the most commonly-used strains in behavioral studies. We assessed the
      recombination efficiency of the CAG-FLPe-Tg lines by crossing them with a mouse
      line carrying a FRT-PGK-neo-FRT cassette. Four of five independent CAG-FLPe lines
      induced recombination in most (91%-100%) of their progenies, although a small
      fraction (0%-30%, depending on the line) showed mosaic recombination patterns.
      These animals are highly potent as deleters of FRT cassettes and are useful for
      behavioral studies involving conditional KO mice.

PMID- 16651698
TI  - Changes in submaxillary gland gene expression in F344 rats by multiple dosing of
      theophylline.
AB  - Multiple exposure to theophylline, a phosphodiesterase (PDE) inhibitor, induces
      acinar hypertrophy in the salivary gland. This study examined the effect of
      theophylline on the gene expression of secretory proteins and phosphodiesterases
      in the submaxillary gland. Male F344 rats received saline or theophylline (50
      mg/kg) intraperitoneally for 4 days. The gene expressions for the secretory
      protein, cystatin S (CysS), and PDE subfamilies 3A and 4D in the submaxillary
      gland were quantified using RT-PCR. Theophylline exposure resulted in a sustained
      increase in mRNA expression for CysS and PDE3A, but PDE4D gene expression was
      unchanged. Our results suggest that submaxillary hypertrophy is primarily caused
      by the enhanced transcription of CysS, and that the transcription of each PDE
      subfamily gene is regulated differently.

PMID- 16651699
TI  - Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets.
AB  - We evaluated the antiemetic effect of zacopride, a potent 5-HT3-receptor
      antagonist with 5-HT4-receptor agonist properties, on delayed emesis caused by
      cisplatin (5 mg/kg, i.p.) in ferrets, compared with granisetron, a selective 5
      HT3-receptor antagonist. Multiple intravenous injections of zacopride at 1 mg/kg,
      a dose that completely inhibited acute emesis caused bycisplatin (10 mg/kg,
      i.v.), significantly reduced delayed emesis. Granisetron (3.2 mg/kg) also reduced
      delayed emesis but this failed to reach statistical significance. The present
      study suggests that a combined 5-HT3-receptor antagonist/5-HT4-receptor agonist,
      like zacopride, may be useful against both acute and delayed emesis induced by
      cancer chemotherapy.

PMID- 16651700
TI  - A critical role of TRPM2 in neuronal cell death by hydrogen peroxide.
AB  - A brief exposure to hydrogen peroxide (H2O2) induces severe deterioration of
      primary cultured neurons in vitro. We have investigated a link between the H2O2
      induced neuronal death and Ca2+-permeable TRPM2 channels regulated by ADP-ribose
      (ADPR). In cultured cerebral cortical neurons from fetal rat, TRPM2 proteins were
      detected at cell bodies and neurite extensions. Application of H2O2 to the
      cultured neurons elicited an increase in intracellular Ca2+ concentration
      ([Ca2+]i) caused by Ca2+ influx and the Ca2+-dependent neuronal death in a
      similar concentration range. Molecular cloning of TRPM2 cDNA from rat brain
      revealed several differences in amino acid sequences within the Nudix box region
      as compared with those of human and mouse TRPM2. ADPR-induced current responses,
      H2O2-induced Ca2+ influx, and H2O2-induced cell death were induced in human
      embryonic kidney cells heterologously expressing rat TRPM2. Treatment of cultured
      neurons with small interfering RNA against rat TRPM2,which efficiently suppressed
      immunoreactive TRPM2 content and the H2O2-induced Ca2+ influx,significantly
      inhibited H2O2-induced neuronal death. These results suggest that TRPM2 plays a
      pivotal role in H2O2-induced neuronal death as redox-sensitive Ca2+-permeable
      channels expressed in neurons.

PMID- 16651701
TI  - A missing link between a high salt intake and blood pressure increase.
AB  - It is widely accepted that a high sodium intake triggers blood pressure rise.
      However, only one-third of the normotensive subjects were reported to show salt
      sensitivity in their blood pressure. Many factors have been proposed as causes of
      salt-sensitive hypertension, but none of them provides a satisfactory
      explanation. We propose, on the basis of accumulated data, that the reduced
      activity of the kallikrein-kinin system in the kidney may provide this link.
      Renal kallikrein is secreted by the distal connecting tubular cells and all
      kallikrein-kinin system components are distributed along the collecting ducts in
      the distal nephron. Bradykinin generated is immediately destroyed by
      carboxypeptidase Y-like exopeptidase and neutral endopeptidase, both quite
      independent from the kininases in plasma, such as angiotensin converting enzyme.
      The salt-sensitivity of the blood pressure depends largely upon ethnicity and
      potassium intake. Interestingly, potassium and ATP-sensitive potassium (K(ATP))
      channel blockers accelerate renal kallikrein secretion and suppress blood
      pressure rises in animal hypertension models. Measurement of urinary kallikrein
      may become necessary in salt-sensitive normotensive and hypertensive subjects.
      Furthermore, pharmaceutical development of renal kallikrein releasers, such as
      K(ATP) channel blockers, and renal kininase inhibitors, such as ebelactone B, may
      lead to the development of novel antihypertensive drugs.

PMID- 16651702
TI  - [Antibodies to citrullinated proteins in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology,
      characterized by chronic joint inflammation that often leads to joint
      destruction. Diagnosis of RA is currently based on the revised classification
      criteria of the American College of Rheumatology (ACR); however, it remains
      imprecise, especially early in the course of disease. Rheumatoid factor (RF) has
      been widely used in clinical practice as a useful serological marker for
      diagnosis of RA. Although RF is the only serological test in the criteria of the
      ACR, its specificity is limited since RF can be also detected in other rheumatic
      diseases. Because the current therapeutic strategies in RA employ increasingly
      aggressive regimens from early stage of the disease, more specific serological
      markers than RF are desirable. Recently, anti-cyclic citrullinated peptide (anti
      CCP) antibodies have attracted attention as a useful marker for the diagnosis of
      RA with high specificity. In addition to the diagnostic properties, anti-CCP
      antibodies showed to be a good prognostic marker for joint destructions. In this
      review, we will explain about the clinical usefulness of anti-CCP antibodies for
      the daily practice of RA.

PMID- 16651703
TI  - [The mechanisms of antinuclear antibody production and its pathogenicity in
      systemic autoimmune diseases].
AB  - Genesis of antinuclear antibodies is one of the most important immunological
      abnormalities that are closely associated with clinical manifestations, disease
      activity, and prognosis of systemic autoimmune diseases. Previous reports
      indicated that autoreactive T cells have critical roles not only in antinuclear
      antibody production but also in organ damages. Recently, the possible molecules
      that are involved in the mechanism of antinuclear antibody production have been
      determined by using lupus-prone mice. Target treatment against the key molecules
      associated with autoreactive T cells and B cells may be the useful therapeutic
      strategy for systemic autoimmune diseases along with the suppression of disease
      specific antinuclear antibody production.

PMID- 16651704
TI  - [The role of cell stress in systemic autoimmune disease].
AB  - Anti-DNA antibody is a characteristic feature of systemic lupus erythematosus
      (SLE) and plays an important role in pathogenesis of lupus nephritis. However,
      the mechanism of anti-DNA antibody production, which may directly link to the
      etiology of SLE, remains uncertain. Mammalian DNA alone is not immunogenic.
      However, some anti-DNA antibodies cross-react with self antigens, and
      immunization of mice with a certain peptide could induce anti-DNA antibodies.
      These facts raise a question as to whether an antigenic trigger of anti-DNA
      antibodies production is DNA itself. Therefore, molecular mimicry of DNA by non
      DNA antigen is a possibility for the initial production of anti-DNA antibodies.
      We found that the human monoclonal nephritogenic anti-DNA antibody, O-81,
      specifically bound to an endoplasmic reticulum stress response protein, Herp.
      This suggests that lupus nephritogenic anti-DNA antibody cross-react with Herp
      and an epitope on Herp mimics DNA. Each time cells receive stress (for example,
      viral infection), the synthesis of Herp protein is induced. If the epitope is
      immunogenic, repetitive cell stress can be a trigger of anti-DNA antibodies
      production.

PMID- 16651705
TI  - [B cell abnormalities and autoantibody production in systemic sclerosis].
AB  - The pathogenetic roles of autoantibodies remain unknown in systemic sclerosis
      (SSc). CD19, a cell-surface critical signal transduction molecule of B
      lymphocytes, augments signaling through B cell antigen receptor and CD19
      overexpression in mice induces various autoantibody production. Peripheral B
      cells from SSc patients exhibit 20%-increase in CD19 expression. Furthermore, B
      cells from a tight-skin (TSK) mouse, a genetic murine model of SSc, show
      augmented signaling through CD19. The deficiency of CD19 expression in TSK mice
      results in inhibition of autoantibody production, reduced skin fibrosis, and
      inhibition of augmented IL-6 production by splenic B cells. Collectively, a new
      model that could explain the relationship between autoantibody and the
      development of fibrosis is proposed. CD19 overexpression observed in SSc patients
      breaks down peripheral tolerance of B cells, which results in autoantibody
      production. Furthermore, it is also possible that in vivo chronic B cell
      activation probably due to CD19 overexpression results in the development of
      fibrosis through production of fibrogenic cytokines, such as IL-6. This model
      indicates that B cells or CD19 would be potential therapeutic targets in SSc.

PMID- 16651706
TI  - [Autoantibodies specifically detected in patients with
      polymyositis/dermatomyositis].
AB  - Polymyositis/Dermatomyositis (PM/DM) is a chronic inflammatory disorder that
      culminates in injury to the skin and muscle and, sometimes, is accompanied by
      interstitial lung disease (ILD). A number of autoantibodies are associated with
      myositis, including those specific for aminoacyl-tRNA synthetase (anti-ARS),
      signal recognition particle (anti-SRP), and Mi-2. These autoantibodies have
      proven to be useful in the diagnosis and classification of the diseases and are
      predictive of prognosis. It has been known that certain patients may have typical
      DM skin manifestations without clinical evidence of myositis for at least 2 years
      (Clinically Amyopathic DM; C-ADM). Although classical myositis-related antibodies
      are well known, specificities related to C-ADM have not been examined in detail.
      Therefore, we have examined sera from 15 Japanese patients with C-ADM to identify
      additional autoantibodies associated with this disease. Eight sera of C-ADM
      patient recognized a polypeptide of approximately 140 kDa and we named this new
      antibody specificity anti-CADM-140. Anti-CADM-140 antibodies were detected in 8
      of 42 patients with DM, but not in patients with other connective tissue diseases
      or idiopathic pulmonary fibrosis. It is noteworthy that DM patients with anti
      CADM-140 had significantly more rapidly progressive ILD when compared to patients
      without anti-CADM-140 (50% vs 6%, P=0.008). Further studies of the pathogenicity
      of these autoantibodies specificity may provide insight into the pathogenic
      mechanisms of PM/DM accompanied by rapidly progressive ILD.

PMID- 16651707
TI  - [Anti-neutrophil cytoplasmic antibody MPO-ANCA related with disease activity of
      vasculitis].
AB  - Myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA)
      are involved in the development of vasculitis microscopic polyangiitis, a
      systemic vasculitis etc. We have showed a correlation of MPO-ANCA epitopes in
      vasculitis concerning contribution of N and C terminus of MPO to severity of the
      diseases. On the other hand, a role of activated neutrophils in inflammatory
      nephritis renal lesions using SCG/Kj mice. In the phase of nephritis with a low
      grade of proteinuria, the spontaneous release of MPO from peripheral neutrophils
      increased, indicating that neutrophils are activated and contribute to the
      development of active crescentic lesions in SCG/Kj mice. In addition, we have
      investigated that mice having CADS/CAWS-induced vasculitis also are good model
      animals for the analysis of the production of MPO-ANCA. Furthermore, we have
      clarified that MPO is a major antigen for MPO-ANCA production using MPO knock
      mice.

PMID- 16651708
TI  - [A case of Good syndrome accompanied by myasthenia gravis: immunological
      evaluations].
AB  - Good syndrome, characterized by both thymoma and hypogammaglobulinemia, is a rare
      immunodeficient disorder. We experienced a case of Good syndrome accompanied by
      myasthenia gravis (MG). A 58-year-old man was admitted to our hospital because of
      muscle weakness and fatigability. Based on the presence of anti-acetylcholine
      receptor (AChR) antibody and thymoma, he was diagnosed as having MG. Peripheral
      blood lymphocyte count was normal, but gammaglobulin levels were markedly
      decreased (IgG 283 mg/dl, IgA 17 mg/dl, IgM 1 mg/dl). Clinical remission of MG
      was achieved by thymectomy followed by high-dose corticosteroids. Despite monthly
      intravenous immunoglobulin supplementation, he suffered from repeated respiratory
      tract infections and candidiasis. Body CT revealed adrenal tumor and pancreatic
      cancer with liver metastasis, and he died of bacterial pneumonia. Immunological
      evaluations showed complete lack of CD19+ B cell in the peripheral blood and
      responses of peripheral blood mononuclear cells to mitogens. Peripheral blood T
      cells responded to a suboptimal concentration of a recombinant AChR fragment:
      this pattern of AChR-induced T cell response was typical of MG patients. We
      failed to detect IgG autoantibodies reactive with B cells in his serum. Patients
      with Good syndrome represent imbalance of immune responses, leading to both
      immunodeficiency and autoimmunity.

PMID- 16651709
TI  - Soybean oil fat emulsion to prevent TPN-induced liver damage: possible molecular
      mechanisms and clinical implications.
AB  - Long-term total parenteral nutrition (TPN) is known to be associated with
      cholestasis and hepatic steatosis, which can be lethal in infants who cannot be
      fed orally. The present review focuses on the metabolic complications in the
      liver that may occur due to the excessive administration of fat-free TPN. We have
      recently developed an infant rat model of hepatic dysfunction and steatosis
      induced by overdose of fat-free TPN. In this model, plasma levels of liver
      enzymes in the fat-free TPN group were found to be significantly higher than in
      the other groups (i.e., the oral diet and fat-containing TPN groups).
      Pathological examination showed hepatomegaly and severe fatty changes without
      cholestasis in the liver of infant rats that received fat-free TPN. We clearly
      demonstrated that the addition of soybean oil emulsion to the TPN regimen
      prevented hepatic dysfunction and fatty changes. In the present review, we
      discuss the molecular mechanism of the hepatic dysfunction induced by fat-free
      TPN and the role of soybean oil fat emulsion in the TPN regimen. We also discuss
      the clinical implications of soybean oil-containing TPN solutions and point out
      the importance of including fat in the TPN regimen in order to prevent the
      hepatic abnormalities associated with the excessive administration of fat-free
      TPN.

PMID- 16651710
TI  - Inhibition of putrescine aminopropyltransferase influences rat liver
      regeneration.
AB  - A close relationship between rat liver regeneration and the concentration ratio
      of spermidine to spermine (spd:spm) was demonstrated by the oral administration
      of trans-4-methylcyclohexylamine (MCHA), a specific inhibitor of putrescine
      aminopropyltransferase. A decrease in recovery rate of remnant liver with MCHA,
      as a percentage index of remnant liver weight to body weight, correlated well
      with a decrease of the spd:spm value, with a correlation coefficient of 0.952 for
      the remnant livers on day 3 after partial hepatectomy. The decrease in recovery
      rate could be explained by a prolonged cell cycle based on the data of the
      proliferating cell nuclear antigen labelling index and mitotic cell index in both
      livers of day 2 and day 3 after partial hepatectomy. The results presented here
      will give a new aspect in the field of polyamine regulation to control cell
      growth in vivo.

PMID- 16651711
TI  - Purification of liver serine protease which activates microsomal glutathione S
      transferase: possible involvement of hepsin.
AB  - Rat liver microsomal glutathione S-transferase (MGST1) is known to be activated
      by trypsin, however, it has not been clarified whether MGST1 is activated by a
      protease present in liver. In the present study we purified the MGST1 activating
      protease from liver microsomes and finally identified that the protease is
      hepsin, a type II transmembrane serine protease. When the protease was incubated
      with the purified MGST1 or liposomal MGST1 at 4 degrees C, MGST1 activity was
      increased 3-4.5 fold after 3-6 d. In electrophoretic and immunoblot analyses
      after the incubation of MGST1 with the protease MGST1 dimer and its degraded
      fragment were detected. These results suggest that the rat liver microsomal
      hepsin functions as MGST1 activating/degrading enzyme.

PMID- 16651712
TI  - Primary structure and properties of ribonuclease Bm2 (RNase Bm2) from Bryopsis
      maxima.
AB  - A base non-specific ribonuclease (RNase Bm2) was isolated from a green algae
      (Ulvophyceae, Bryopsis maxima) as a single band on SDS-PAGE, and its primary
      structure and enzymatic properties, including base specificity, were
      investigated. The amino acid sequence of RNase Bm2 was homologous to many RNase
      T2 family RNases, and their characteristic CAS sequences were also conserved. The
      molecular mass of RNase Bm2 was 24444 Da, and its optimal pH was 5.5. RNase Bm2
      was a poly U preferential RNase, similar to RNase MC1 from bitter gourd. The base
      specificity of this RNase suggested that the base specificity of the B1- and B2
      base binding sites of RNase Bm2 were G > or = U > C >> A and U > G > C >> A,
      respectively. The estimated active site of RNase Bm2 was very similar to that of
      RNase MC1 from bitter gourds; however, a tyrosine residue at the B1-base binding
      site that is conserved for all RNase T2 family RNases was replaced by a
      tryptophan residue. Here we discuss the effect of this replacement on the base
      specificity of RNase Bm2 and the phylogenetic relationship of RNase T2 family
      enzymes.

PMID- 16651713
TI  - Anti-inflammatory activity of Ailanthus altissima in ovalbumin-induced lung
      inflammation.
AB  - As part of an ongoing investigation to find bioactive medicinal herbs exerting
      anti-inflammation activity, the effect of an ethanol extract from the parts of
      Ailanthus altissima (Simaroubaceae) was evaluated in both in vitro and in in vivo
      system. The ethanol extract of A. altissima (EAa) inhibited generation of the
      cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 in bone marrow
      derived mast cells (BMMC) in a concentration-dependent manner with an IC50 value
      of 214.6 microg/ml. However, this compound did not inhibit COX-2 protein
      expression up to a concentration of 400 microg/ml in the BMMC, indicating that
      EAa directly inhibits COX-2 activity. In addition, EAa inhibited leukotriene C4
      production with an IC50 value of 25.7 microg/ml. Furthermore, this compound
      inhibited degranulation reaction in a dose dependent manner, with an IC50 value
      of 27.3 microg/ml. Ovalbumin (OVA)-sensitized mice were orally pretreated with
      EAa before aerosol challenges. EAa reduced the eosinophil infiltration into the
      airway and the eotaxin, IL-4, and IL-13 mRNA expression levels. These results
      suggest that the anti-inflammation activity of A. altissima in OVA-induced lung
      inflammation may occur in part via the down regulation of T(H)2 cytokines and
      eotaxin transcripts as well as the inhibition of inflammatory mediators.

PMID- 16651714
TI  - Augmentation of Ca2+-induced microsomal triglyceride transfer protein activity by
      glucose supply enhances hypertriglyceridemia in vivo.
AB  - We have investigated possible roles of intra-glucose supply on microsomal
      triglyceride (TG) transfer protein (MTP) in the secretion of TG-rich very low
      density lipoprotein (VLDL) from the liver. Due to the activation of MTP, TG and
      apolipoprotein B (apoB) in the liver are assembled into VLDL and then the VLDL is
      transferred into the blood stream. High MTP activity can increase the release of
      VLDL into the blood stream, and this would lead high levels of TG and apoB in the
      blood. High MTP activity was found when the liver (or hepatocytes) contained a
      high level of total Ca2+ as a response of glucose administration. However, the
      MTP activity was reduced in response to the calmodulin antagonist N-(6
      aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7, Ki=25 microM), the
      intracellular Ca2+ chelator BAPTA-AM, and the extracellular Ca2+ chelator EDTA.
      These suggested that there might be a very close relationship between high MTP
      activity and high Ca2+ level in the liver by glucose administration. Glucose
      derived hyperglycemic condition resulted from those elevations of TG and total
      cholesterol in the liver. This hyperglycemic phenomenon may be associated with
      the increase of TG and apoB levels in blood. The possibility for the regulation
      of VLDL formation in the liver and, further, those related circulatory diseases
      due to the excess of VLDL in the blood stream by controlling MTP activity in
      association with Ca2+ was investigated.

PMID- 16651715
TI  - The effect of AgK114 on wound healing.
AB  - AgK114 is a newly isolated membrane-associated protein which is expressed on
      keratinocytes. Its expression is restricted to dermal sheath cells near sebaceous
      glands in normal skin. However, it is transiently induced by UV exposure or
      injury stimulation (Tatefuji T. et al., Biol. Pharm. Bull., 27, 1742-1749, 2004).
      Thus, the expression pattern of AgK114 suggested its potential role in wound
      healing response. We report here that expression of AgK114 is induced in the
      initial 24 h at the edge keratinocytes during keratinocyte migration, followed by
      disappearance once epithelialization is completed in the murine excisional wound
      model. We also demonstrate that exogenous recombinant mouse AgK114FL promoted
      wound healing process. Mouse AgK114FL up-regulated pro-matrix-metalloproteinase
      9, vascular endothelial growth factor, transforming growth factor-beta, IL-6, and
      IL-1beta production in the early stage of wound tissue. Moreover, mouse AgK114FL
      induced the matrix-metalloproteinase-9 activity of wound fibroblasts prepared
      from impaired skin in the presence of proinflammatory cytokines. These results
      suggest that the AgK114 participates in the wound response during the healing
      process, and promotes wound repair.

PMID- 16651716
TI  - let-7 microRNA functions as a potential growth suppressor in human colon cancer
      cells.
AB  - MicroRNAs (miRNAs) are endogenously expressed RNAs, 18-25 nucleotides in length,
      that repress protein translation through binding to target mRNAs. miRNAs have
      been implicated in many cellular processes including cell proliferation,
      differentiation, and death. Recently, let-7 miRNAs were found to regulate human
      RAS oncogene expression and to be often down-regulated in human lung tumors. In
      this study, we examined the expression of let-7 miRNAs in human colon cancer
      tumors and cell lines, with the result that 2 of 6 cases and 1 of 3 cell lines
      showed reduced expression of let-7. When let-7 low-expressing DLD-1 human colon
      cancer cells were transfected with let-7a-1 precursor miRNA, which is located at
      chromosome 9q22.3, the cells underwent significant growth suppression. At that
      time, the levels of RAS and c-myc proteins were lowered after the transfection,
      whereas the levels of both of their mRNAs remained almost unchanged. These
      findings suggest the involvement of let-7 miRNA in the growth of colon cancer
      cells. Thus, miRNAs might provide a basis for novel RNA anti-cancer agents.

PMID- 16651717
TI  - Synthetic peptide (P-21) derived from Asp-hemolysin inhibits the induction of
      apoptosis on HUVECs by lysophosphatidylcholine.
AB  - Lysophosphatidylcholine (LPC), formed during low-density lipoprotein (LDL)
      oxidation and located within atherosclerotic plaques, regulates a variety of
      cellular functions, some of which could be construed to promote atherosclerotic
      lesion development, including vascular muscle cell proliferation, monocyte
      attraction, and endothelial cell apoptosis. We have previously reported that the
      synthetic peptide derived from Asp-hemolysin, named P-21, inhibits oxidized LDL
      (OxLDL)-induced macrophage proliferation through binding of P-21 to OxLDL. In
      this study, to clarify the interaction between P-21 and LPC as a typical lipid
      moiety of OxLDL, we examined the influence of P-21 on LPC-induced apoptosis in
      human umbilical vein endothelial cells (HUVECs). Based on flow cytometric
      analysis, using annexin V-fluorescein isothiocyanate and propidium iodide as
      probes to assess apoptosis, LPC induced the apoptosis of HUVECs, and P-21
      significantly inhibited this activity by 82.4%. Furthermore, dissociation
      enhanced lanthanide fluorometric immunoassay indicated that LPC inhibited the
      binding of P-21 to OxLDL in a dose-dependent manner. A 50% inhibition dose was
      estimated to be 4.65 microM of LPC. These results suggest that P-21 inhibits LPC
      induced HUVEC apoptosis through binding of P-21 to LPC.

PMID- 16651718
TI  - Vibrio vulnificus vulnibactin, but not metalloprotease VvpE, is essentially
      required for iron-uptake from human holotransferrin.
AB  - The roles of metalloprotease (VvpE) and catechol-siderophore (vulnibactin) in the
      uptake of iron from human transferrins by Vibrio vulnificus have been determined
      using different experimental conditions and methods. Therefore, in this study, we
      attempted to elucidate the roles of VvpE and vulnibactin using the same methods
      and experimental conditions, in an in vitro and a human ex vivo system, and in
      accordance with the molecular version of Koch's postulates. Neither vvpE mutation
      nor in trans vvpE complementation affected vulnibactin production, iron
      assimilation from human holotransferrin (HT), and bacterial growth in a HT
      containing deferrated Heart-Infusion medium (HT-DF-HI) or a HT-containing
      cirrhotic ascites (HT-CA). In contrast, the mutation of fur gene encoding Fur, a
      repressor regulating expression of the vulnibactin-mediated iron-uptake system,
      derepressed vulnibactin production, and facilitated iron-assimilation from HT and
      bacterial growth in HT-DF-HI or HT-CA. The mutation of vis gene encoding
      isochorismate synthase required for vulnibactin synthesis abolished vulnibactin
      production, iron-assimilation from HT and bacterial growth in HT-DF-HI or HT-CA.
      These results demonstrate that vulnibactin is essentially required for iron
      assimilation from transferrin, and that VvpE has no direct effect on facilitating
      vulnibactin-mediated iron-assimilation from transferrin in vitro or in a human ex
      vivo system.

PMID- 16651719
TI  - Effects of antifungal drugs on proliferation signals in Candida albicans.
AB  - The sensitivity of Candida albicans to antifungal drugs when cultured under
      aerobic and anaerobic conditions was measured. Ciclopirox olamine and siccanin
      were more effective under aerobic than under anaerobic conditions. Terbinafine,
      neticonazole and amphotericin B showed the same antifungal activity under both
      aerobic and anaerobic conditions. None of these antifungal activities were
      affected by the pH conditions. Terbinafine inhibited the elongation of hyphae,
      while neticonazole and amphotericin B induced proliferation of the yeast form.
      The expression of RAS1, EFG1 and CPH1 mRNAs was inhibited by these drugs. These
      results suggested that the inhibition of hyphal formation might be caused by
      disruption of the RAS1-signal pathway.

PMID- 16651720
TI  - Mechanism of Candida albicans transformation in response to changes of pH.
AB  - Hyphal growth of Candida albicans was observed at neutral condition, whereas the
      yeast growth was increased below pH 5. Eight out of 12 strains of C. albicans
      grow in hyphal form at pH 7, and hyphal formation was inhibited in all strains at
      pH 4. The addition of GMP, an alternative oxidase (AOX) activator, induced the
      hyphal growth at pH 4. Although C. albicans grew in hyphal form in pH 7, SHAM, an
      AOX inhibitor, enhanced the yeast proliferation at this pH. The relative
      expression level of RAS1 mRNA was higher at pH 7 than at pH 4, indicating that
      the hyphal formation signal was defective under acidic conditions. Based on these
      findings, we concluded that AOX-RAS1 signal transduction is the main pathway of
      hyphal formation of C. albicans, and that the signal was controlled by pH
      condition.

PMID- 16651721
TI  - Surface plasmon resonance analysis for the screening of anti-prion compounds.
AB  - The interaction of anti-prion compounds and amyloid binding dyes with a carboxy
      terminal domain of prion protein (PrP121-231) was examined using surface plasmon
      resonance (SPR) and compared with inhibition activities of abnormal PrP formation
      in scrapie-infected cells. Most examined compounds had affinities for PrP121-231:
      antimalarials had low affinities, whereas Congo red, phthalocyanine and
      thioflavin S had high affinities. The SPR binding response correlated with the
      inhibition activity of abnormal PrP formation. Several drugs were screened using
      SPR to verify the findings: propranolol was identified as a new anti-prion
      compound. This fact indicates that drug screenings by this assay are useful.

PMID- 16651722
TI  - Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal
      injuries in Dahl salt-sensitive rats.
AB  - The sympathetic nerve activity plays an important role on the renal function
      through the vasoactive system and the renin-angiotensin system. Although interest
      in the renal protective effects of anti-sympathetic agents has been increased,
      there are not enough data to clarify this efficiency. Therefore, we investigated
      the effects of L/N-type calcium channel antagonist, cilnidipine on progressive
      renal injury in Dahl salt-sensitive (Dahl S) rats. Male Dahl S rats (6 weeks of
      age) were fed a high salt (4% NaCl) diet. They were divided into groups with
      similar blood pressure at 12 weeks of age and they received vehicle (n=7) or
      cilnidipine (30 mg/kg/d as food admix, n=9) for 8 weeks. Cilnidipine treatment
      suppressed the increase in systolic blood pressure. Although urinary protein
      excretion was not influenced, cilnidipine inhibited the increase in blood urea
      nitrogen and decrease in creatinine clearance. Histological investigation
      revealed that progression of glomerular sclerosis was inhibited in cilnidipine
      treatment group. Of notes, cilnidipine reduced plasma norepinephrine level and
      plasma rennin activity compared with vehicle-treated Dahl S rats. These data
      indicated that cilnidipine has suppressive effects against progressive renal
      injury in Dahl S rats. This effect is not only explained by the L-type calcium
      channel blocking action that lowered blood pressure, but also partially explained
      by the N-type calcium channel blocking action that lead to suppression of the
      sympathetic nerve activity and renin-angiotensin system.

PMID- 16651723
TI  - Ethanolic extracts from Curcuma longa attenuates behavioral, immune, and
      neuroendocrine alterations in a rat chronic mild stress model.
AB  - The ethanolic extracts from the rhizome of Curcuma longa L. (turmeric), possesses
      a wide variety of biological activities related to the treatment and prevention
      of affective disorders. To study their antidepressant effects, the impacts of
      chronic mild stress (CMS) and of the subsequent administration of ethanolic
      extracts of C. longa were investigated. Male Sprague-Dawley rats subjected to the
      CMS procedure demonstrated increased serum interleukin-6 and tumor necrosis
      factor-alpha levels, as well as a reduction of natural killer cell activity in
      splenocytes. In addition, CMS-treated rats exhibited elevated corticotropin
      releasing factor in serum and medulla oblongata and cortisol levels in serum,
      with no significant change in serum adrenocorticotropin hormone levels. The
      preferential behavior of reduction in sucrose intake was also observed. These
      findings indicate that the alterations in immune and hypothalamic-pituitary
      adrenal (HPA) axis systems could participate in the behavioral response to the
      CMS procedure in animals. Administration of ethanolic extracts of C. longa
      largely reversed the above effects. These results demonstrate the antidepressant
      like activity of ethanolic extracts of C. longa in the rat CMS model of
      depression, at least in part by improving the abnormalities in immune and the HPA
      axis functions.

PMID- 16651724
TI  - Puerarin induces angiogenesis in myocardium of rat with myocardial infarction.
AB  - Puerarin is a major effective ingredient extracted from the traditional Chinese
      medicine ge-gen (radix puerariae, RP). Recently, puerarin has been used to treat
      patients with coronary artery diseases (CAD). However, the mechanisms of puerarin
      on coronary artery diseases are still not very clear. In this study, we
      investigated the role of puerarin on angiogenesis in the non-ischemic and
      ischemic myocardium. We found that puerarin (120, 60 mg/kg, i.p.) could reduce
      infarct area in the heart of rat with myocardial infarction (MI). Puerarin (120
      mg/kg) induced angiogenesis in the non-ischemic and ischemic myocardium, which
      was one of the mechanisms of curing coronary artery diseases. The gene expression
      or activation of vascular endothelial growth factor (VEGF), hypoxia-inducible
      factor 1alpha (HIF-1alpha) and endothelial nitric oxide synthase (eNOS) that
      correlated with angiogenesis were also induced by puerarin. From these results,
      we suggested that puerarin may induce therapeutic angiogenesis in myocardium of
      rat with MI. The mechanism may be that puerarin can induce VEGF and eNOS
      expression.

PMID- 16651725
TI  - In vitro assessment of plasma protein binding of 20(R)-ginsenoside Rh2 by
      equilibrium dialysis and LC-MS analysis: a case of species differences.
AB  - 20(R)-Ginsenoside Rh2 is isolated from Chinese traditional ginsengs with main
      antitumor effects. To support its pharmacokinetic study which was essential for
      the pre-clinical research for new drug development, in this paper, 20(R)-Rh2
      plasma protein binding was assessed in vitro at four concentration levels (50,
      100, 200, 400 ng/ml) both in rat and human plasma using equilibrium dialysis and
      followed by LC-MS analysis. The method was optimized against some influencing
      factors during both experimental procedures. And it was validated to be specific,
      sensitive, accurate, precise and of satisfactory recovery. The results showed the
      binding fractions were about 70% for rats and 27% for human within four
      concentration levels. It exhibited a significant species difference between human
      and rats for the plasma protein binding of 20(R)-Rh2.

PMID- 16651726
TI  - Neuroprotective effects of trolox in global cerebral ischemia in gerbils.
AB  - Stroke is a third leading cause of death and oxygen free radicals have been shown
      to be involved in its pathophysiology. In the present study, we have investigated
      neuroprotective potential of trolox, a free radical scavenger in bilateral
      carotid arteries occlusion (5 min) model of global cerebral ischemia in Mongolian
      gerbils. Gerbils were treated with trolox (3, 10 or 30 mg/kg, i.p.) 30 min prior
      to occlusion. There was a significant increase in neurological symptoms and
      locomotor activity in ischemic animals as compared with the sham-operated
      animals. These effects were attenuated by trolox 30 mg/kg, i.p. Significant
      increase in the number of the surviving neurons in the hippocampal CA1 pyramidal
      region was observed in ischemic animals treated with trolox 30 mg/kg, i.p. There
      was significant increase in the level of malondialdehyde (MDA) in ischemic
      animals indicating oxidative stress. Elevated levels of MDA in ischemic animals
      (25.79+/-3.34 microM/mg of protein) were reduced (16.43+/-3.32 microM/mg of
      protein) and (8.98+/-0.89 microM/mg of protein) by trolox 10 and 30 mg/kg, i.p.,
      respectively. This study demonstrates the neuroprotective potential of trolox in
      global cerebral ischemia in gerbils.

PMID- 16651727
TI  - Aged garlic extract ameliorates physical fatigue.
AB  - Aged garlic extract (AGE) has recently received attention as a potent anti
      fatigue agent. The principal aim of this study was to elucidate the mechanism
      responsible for the ameliorating effect of AGE on physical fatigue in rats caused
      by repeated endurance exercise on a mechanical treadmill apparatus. Rats were
      subjected to endurance exercise 5 times per week for 4 weeks. AGE at a dosage of
      2.86 g/kg was administrated to rats 30 min before every exercise. Succinate
      dehydrogenase (SDH) activity in the gastrocnemius and soleus muscles and
      superoxide dismutase (SOD) activity, nitric oxide (NO) metabolites, and lactic
      acid concentration in plasma were evaluated as biomarkers of physical fatigue.
      SDH activity was increased 2-4-fold by repeated endurance exercise in comparison
      with unexercised (intact) rats, and AGE further up-regulated this activity by
      40%. SOD activity was increased 5-fold, whereas AGE maintained it at a level
      equivalent to that in intact rats. Levels of NO metabolites were slightly
      decreased, whereas AGE enhanced them 2-fold. Lactic acid concentration was not
      changed in any of the groups. These results indicate that AGE may facilitate the
      turnover of aerobic glucose metabolism, attenuate oxidative stress, and promote
      oxygen supply based on vasodilation, suggesting that AGE ameliorates the various
      impairments associated with physical fatigue.

PMID- 16651728
TI  - The anti-gastropathic and anti-rheumatic effect of niga-ichigoside F1 and 23
      hydroxytormentic acid isolated from the unripe fruits of Rubus coreanus in a rat
      model.
AB  - This study was undertaken to produce the clinical merits of two natural
      antinociceptive anti-inflammatory triterpenoids which synthetic anti-inflammatory
      drugs do not have. The triterpenoid glycoside niga-ichigoside F1 (NIF1) and its
      aglycone 23-hydroxytormentic acid (23-HTA), which were isolated from the unripe
      fruits of Rubus coreanus (Rosaceae), reduced rheumatoid arthritis (RA) factor and
      C-reactive protein (CRP) factor in Freund's complete adjuvant reagent-induced
      rats, suggesting that these two triterpenoids had an anti-rheumatic effect. It
      was also shown that treatment with NIF1 or 23-HTA reduced gastric lesion extent,
      acidity and total gastric acid output induced by EtOH plus sodium salicylate in a
      gastric secretion test. Moreover, 23-HTA had a greater effect than the glycoside,
      NIF1. To clarify the anti-gastropathic mechanism of these two compounds, their
      free radical scavenging activities in the gastric mucosa were examined in a rat
      EtOH-sodium salicylate-induced gastropathy model. The two compounds significantly
      increased superoxide dismutase and glutathione peroxidase activities, indicating
      that the healing effects of NIF1 and 23-HTA against gastropathy are associated
      with free radical scavenging enzyme activities. These results support the notion
      that the long-term administration of NIF1 or 23-HTA should overcome the adverse
      effects of synthetic anti-inflammatory drugs.

PMID- 16651729
TI  - The anti-inflammatory and anti-nociceptive effects of ethyl acetate fraction of
      cynanchi paniculati radix.
AB  - The anti-inflammatory and anti-nociceptive effects and sedative activities of the
      ethyl acetate fraction of Cynanchum paniculatum (EACP) were evaluated in mice and
      rats by acetic acid-induced vascular permeability, arachidonic acid-induced paw
      edema, cotton pellet-induced granuloma formation, formalin-induced licking time,
      acetic acid-induced writhing response, and pentobarbital-induced sleeping time.
      EACP at a dose of 40 mg/kg significantly exhibited anti-inflammatory activities
      on acetic acid-induced vascular permeability, arachidonic acid-induced paw edema,
      and the late phase of formalin-induced licking time. Moreover, it showed anti
      nociceptive effects on acetic acid-induced writhing responses and significant
      sedative effects on pentobarbital-induced sleeping time. The results demonstrated
      that the anti-nociceptive effects are apparently related to the sedative effects
      of EACP. These results support the use of Cynanchum paniculatum in relieving
      inflammatory pain.

PMID- 16651730
TI  - Inhibition of nuclear factor-kappaB activation by 2',8''-biapigenin.
AB  - Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play a key
      role in the inflammatory processes. Improper overproduction of NO and
      prostaglandins by both enzymes are also believed to be involved in the
      pathogenesis of certain human cancers. Crude extracts of Selaginella tamariscina
      are used as an oriental medicine, which has been reported to inhibit the
      production of proinflammatory cytokines and cause cell cycle arrest. We isolated
      2',8''-biapigenin from S. tamariscina and investigated whether it modulates iNOS
      and COX-2 expressions in Raw264.7 macrophages stimulated with lipopolysaccharide
      (LPS). We found that 2',8''-biapigenin blocked the transactivations of iNOS and
      COX-2 genes via the inactivation of nuclear factor-kappaB by preventing the
      nuclear translocation of p65. Hence, it may be possible to develop S. tamariscina
      extracts or 2',8''-biapigenin as a useful agent for cancer chemoprevention or for
      the treatment of inflammatory diseases.

PMID- 16651731
TI  - Molecular target of decursins in the inhibition of lipid droplet accumulation in
      macrophages.
AB  - During screening for inhibitors of lipid droplet accumulation in mouse peritoneal
      macrophages, two coumarins identified as decursin and decursinol angelate were
      isolated from the roots of Angelicae gigantis. The cellular molecular target of
      these inhibitors in macrophages was studied. Decursin and decursinol angelate
      inhibited cholesteryl ester (CE) synthesis with IC50 values of 9.7 and 10.1
      microM, respectively, whereas they enhanced triacylglycerol (TG) synthesis.
      Lysosomal metabolism of cholesterol to CE was inhibited by the compounds,
      indicating that the site of inhibition is one of the steps between the exiting of
      cholesterol from the lysosomes and CE synthesis in the endoplasmic reticulum.
      Therefore, acyl-CoA:cholesterol acyltransferase (ACAT) activity in the microsomal
      fractions prepared from mouse macrophages was studied, and the results showed
      inhibition of this activity by decursin and decursinol angelate with IC50 values
      of 43 and 22 microM, respectively. Thus, it was concluded that the compounds
      inhibit macrophage ACAT activity to decrease CE synthesis, leading to a reduction
      of lipid droplets in macrophages.

PMID- 16651732
TI  - Preventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide
      induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via
      suppression of nuclear factor-kappaB in RAW 264.7 cells.
AB  - During our ongoing efforts to identify bioactive natural products with anti
      inflammatory activity, we produced an extract from Ginkgo biloba (GBB) which
      contains higher levels of the active principles terpene and biflavonoid than EGb,
      the standard commercially available extract. In the present study, we examined
      and compared the effects of these two extracts on lipopolysaccharide (LPS)
      induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7
      macrophage cell line. Our data indicate that GBB is a more potent inhibitor of NO
      and PGE2 production than EGb 761, and it also significantly decreased tumor
      necrosis factor (TNF)-alpha release. Consistent with these observations, the
      protein and mRNA expression levels of inducible NO synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were found to be inhibited by GBB in a dose-dependent
      manner. Furthermore, GBB inhibited the LPS-induced DNA binding activity of
      nuclear factor-kappaB (NF-kappaB), which was associated with the prevention of
      IkappaB degradation, and subsequently with decreased p65 protein level in the
      nucleus. These results suggest that GBB inhibits LPS-induced iNOS, COX-2 and TNF
      alpha expressions through the down-regulation of NF-kappaB-DNA binding activity.

PMID- 16651733
TI  - Regulators for blood glucose level affect gene expression of aquaporin 3.
AB  - Aquaporin 3 (AQP3), a membrane protein, is known to permeabilize water and other
      small molecules such as glycerol and urea and is localized in the bowel, skin,
      kidney, and erythrocytes. Since glycerol is a nutrient and serves as a source
      material in glycolytic metabolism, absorption of glycerol in the gastrointestinal
      tract may be under some control. Therefore we first investigated whether insulin
      regulating the glycolytic pathway took part in glycerol transport through AQP3 in
      the gastrointestinal tract and found that insulin significantly suppressed mRNA
      and protein expressions of AQP3 in Caco-2 cells. The antidiabetic drugs
      troglitazone and tolbutamide were also observed to suppress significantly AQP3
      expression, but the biguanides metformin and buformin did not induce such
      suppression. Epinephrine was found to increase expression of AQP3, although
      glucagon showed no change of expression. Wortmannin and rapamycin were
      demonstrated to deactivate suppression of AQP3 expression by insulin and
      troglitazone, suggesting that the signal transducers, phosphoinositide 3 kinase
      (PI3K) and the mammalian target of rapamycin (mTOR), are involved in the signal
      pathway for regulating transcription of AQP3.

PMID- 16651734
TI  - The extracellular pH dependency of transport activity by human oligopeptide
      transporter 1 (hPEPT1) expressed stably in Chinese hamster ovary (CHO) cells: a
      reason for the bell-shaped activity versus pH.
AB  - Human oligopeptide transporter (hPEPT1) translocates di/tri-peptide by coupling
      to movement of proton down the electrochemical gradient. This transporter has the
      characteristics that the pH-profile of neutral dipeptide transport shows a bell
      shaped curve with an optimal pH of 5.5. In the present study, we examined the
      reason for the decrease in the acidic region with hPEPT1-transfected CHO cells
      stably oeverexpressing hPEPT1 (CHO/hPEPT1). The pH profile of the transport
      activity vs. pH was measured in the presence of nigericin/monensin. Under this
      condition, the inwardly directed proton concentration gradient was dissipated
      while the membrane potential remained. As pH increased the activity increased,
      and the Henderson-Hasselbalch equation with a single pKa was fitted well to the
      activity curve. The pKa value was estimated to be 6.7+/-0.2. This value strongly
      suggests that there is a key amino acid residue, which is involved in pH
      regulation of transport activity. To identify the key amino acid residue, we
      examined the effects of various chemical modifications on pH-profile of the
      transport activity. Modification of carboxyl groups or hydroxyl groups had no
      significant influence on the pH-profile, whereas a chemical modification of
      histidine residue with diethylpyrocarbonate (DEPC) completely abolished the
      transport activity in CHO/hPEPT1 cells. On the other hand, this abolishment was
      almost prevented by the presence of 10 mM Gly-Sar. This protection was observed
      only in the presence of the substrate of hPEPT1, indicating that the histidine
      residue is located at the substrate recognition site. The pH-profile of the
      transport activity in CHO/hPEPT1 cells treated with DEPC in the presence of 10 mM
      Gly-Sar also showed a bell-shape similar to that in non-treated CHO/hPEPT1 cells.
      These data stressed that the histidine residue located at or near the substrate
      binding site is involved in the pH regulation of transport activity.

PMID- 16651735
TI  - Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase.
AB  - The biguanides metformin and buformin, which are clinically used for diabetes
      mellitus, are known to improve resistance to insulin in patients. Biguanides were
      reported to cause lactic acidosis as a side effect. Since the mechanism of the
      side effect still remains obscure, we have examined genes whose expression
      changes by treating HepG2 cells with buformin in order to elucidate the
      mechanisms of the side effect. A subtraction cDNA library was constructed by the
      method of suppressive subtractive hybridization and the screening of the library
      was performed with cDNA probes prepared from HepG2 cells treated with or without
      buformin for 12 h. The expression of the gene and the protein obtained by the
      screening was monitored by real-time RT-PCR with specific primers and Western
      blotting with specific antibody. The amounts of ATP and NAD+ were determined with
      luciferase and alcohol dehydrogenase, respectively. We found that expression of
      the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by
      treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library
      screening. The decrease in the expression depended on the treatment period. The
      amount of GAPD protein also decreased simultaneously with the suppression of the
      gene expression by the treatment with buformin. The amount of ATP and NAD+ in the
      HepG2 cells treated with buformin decreased to 10 and 20% of the control,
      respectively. These observations imply that the biguanide causes deactivation of
      the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and
      a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate
      dehydrogenase leans towards lactate production and this may result in lactic
      acidosis.

PMID- 16651736
TI  - Preparation of neocarzinostatin apoprotein mutants and the randomized library on
      the chromophore-binding cavity.
AB  - W39F, F52Y, S98G, S98A, and S98C mutants of the neocarzinostatin apoprotein (apo
      NCS) were newly prepared and investigated their physicochemical properties. The
      circular dichroism (CD) spectra of F78W, F52Y, S98A, S98G, S98C were
      superimposable with that of wild type 1R49 protein although the minor spectral
      change seemed to be in the ellipticity of W39F. The results suggest that position
      52, 78, and 98 involving natural chromophore binding do not play a major role in
      the inducing overall structural changes of the protein. Conversely, the position
      39 would be affected slightly. Ethidium bromide (EtdBr) binding to mutants was
      also evaluated by the monitoring of total fluorescence intensity and fluorescence
      polarization (FP). The observed dissociation constant in the FP study was 4.4
      microM for wild type, 2.2 microM for S98A, 1.3 microM for S98G, 9.7 microM for
      S98C, respectively. When S98G and F52Y, the calculated maximum change of the
      total fluorescence intensity was increased, suggesting that the EtdBr binding to
      S98G or F52Y were slightly improved compared with the wild type. Then, a total of
      14 amino acids randomly substituted phage displayed library of apo-NCS was
      successfully prepared, because substitution of the amino acid structured the
      chromophore-binding cavity were not change the overall structural features. The
      phages which bound glycyrrhetic acid conjugated bovine serum albumin were
      enriched from this library using phage display technique as the pilot
      experiments. Although more precision investigation still needs, it should be
      possible to select variants that have new functions not found in nature.

PMID- 16651737
TI  - Increment of plasma soluble CD14 level in carrageenan-primed endotoxin shock
      model mice.
AB  - CD14 is membrane-associating or free soluble glycoprotein which recognizes
      lipopolysaccharide (LPS) and is assumed to be involved in the onset of endotoxin
      shock. There are some reports suggesting the relationship between increased
      expression of CD14 in infectious or inflammatory diseases. However, little has
      been reported concerning the soluble CD14 (sCD14) level, especially in mice. In
      this study, we measured the plasma level of sCD14, TNF-alpha and IL-6 in the iota
      carrageenan (CAR)-primed endotoxin shock model in addition to the D-galactosamine
      (D-galN)-primed endotoxin shock model mice. It was confirmed that all mice were
      dead within 12 h after a higher dose of LPS-treatment in both animal models. The
      level of TNF-alpha, IL-6 and sCD14 significantly increased in the CAR-primed
      endotoxin shock model mice. However, the D-galN-primed endotoxin shock model mice
      showed only a slight increment of TNF-alpha and IL-6 level, and sCD14 was below
      the detectable level. In the examination using several doses of LPS in CAR-primed
      model mice, IL-6 and sCD14 were increased dependent on the LPS dose, but TNF
      alpha remained at an almost equal level at any dose of LPS in this study
      condition. In conclusion, the production of TNF-alpha, IL-6 and sCD14 was
      significantly enhanced in the CAR-primed model mice, compared to the D-galN
      primed model mice. Therefore, these data indicate the possibility that the sCD14
      level did not increase consistently, even under a fatal condition in endotoxin
      shock. Also, CAR-primed endotoxin shock would be an important experimental model
      to examine the elevation mechanisms for sCD14 and IL-6 production.

PMID- 16651738
TI  - Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic
      leukemia (APL) patient: speciation of arsenic metabolites in serum and urine.
AB  - The pharmacokinetics of arsenic species in a Japanese patient with relapsed acute
      promyelocytic leukemia (APL) treated with arsenic trioxide at a daily dose of
      0.08 mg/kg was investigated. After achieving complete remission on Day 35 during
      the induction therapy of arsenic trioxide, we collected the serum and urine
      samples on Days 4 and 5 during the consolidation therapy of arsenic trioxide. The
      concentrations of inorganic arsenic and the methylated metabolites in serum and
      urine were measured by HPLC/ICP-MS. The patient restricted taking the seafood for
      3 d before the start of administration and during the sampling period in order to
      avoid the influence of arsenic derived from seafood. Arsenite (As(III)),
      methylarsonic acid (MMAs(V)), and dimethylarsinic acid (DMAs(V)) were detected in
      serum and urine. The total concentration of As(III), MMAs(V) and DMAs(V) in serum
      ranged from 18 to 41 microg/l (240-547 nM) during 24 h on Day 4. The amount of
      total arsenic (As(III)+MMAs(V)+DMAs(V)) in urine was 4464 microg/d on Day 4.
      These results suggest that not the micro-molar but the nano-molar order of
      arsenic in serum is sufficient to produce the therapeutic effect on APL cells.

PMID- 16651739
TI  - Anti-angiogenic and anti-tumor activities of 2'-hydroxy-4'-methoxychalcone.
AB  - In the present study, we evaluated the in vitro and in vivo anti-angiogenic and
      anti-tumor activities of 2'-hydroxy-4'-methoxychalcone (HMC). HMC decreased
      angiogenesis in both chick embryos in the chorioallantoic membrane assay and
      basic fibroblast growth factor (bFGF)-induced vessel formation in the mouse
      Matrigel plug assay. This compound also reduced the proliferation of calf
      pulmonary arterial endothelial cells and was found to possess relatively weak
      gelatinase/collagenase inhibitory activity in vitro. HMC, when administered
      subcutaneously at the dose of 30 mg/kg for 20 d to mice implanted with murine
      Lewis lung carcinoma, caused a significant inhibition of tumor volume by 27.2%.
      Intraperitoneal (i.p.) treatment at the same dosage for 10 d to ICR mice bearing
      sarcoma 180 caused a significant suppression in tumor weight by 33.7%. Taken
      together, out data demonstrate that the anti-angiogenic activities of HMC might
      be due to anti-proliferative activity under inhibition of the induction of COX-2
      enzyme. Furthermore, the results suggest that the potent anti-angiogenic activity
      of HMC seems to be the possible mechanism of action in these animal models of
      solid tumors.

PMID- 16651740
TI  - Expression and regulation of breast cancer resistance protein and multidrug
      resistance associated protein 2 in BALB/c mice.
AB  - Microsomal enzyme inducers are known to influence the expression of many
      transporter proteins and mRNA. In this study, we examined the effects of
      microsomal enzyme inducers on the mRNA expression of Breast Cancer Resistance
      Protein (BCRP) and Multidrug Resistance Associated Protein 2 (MRP2) in BALB/c
      mice. mRNA expression in liver, duodenum, jejunum and ileum was examined in mice,
      which were treated with microsomal enzyme inducers-aryl hydrocarbon receptor
      (AhR) ligands 3-methylcholanthrene (3-MC) and pregnane-x-receptor (PXR) ligand
      pregenolone-16alpha-carbonitrile (PCN) and compared with control vehicle. The
      results suggested that the expression level of bcrp mRNA in the ileum was twice
      that in the liver, duodenum and jejunum using both semi quantitative PCR and Real
      time PCR. Mrp2 mRNA was significantly increased by both PCN and 3-MC treatment.
      In contrast, bcrp mRNA expression was not significantly affected by these
      inducers. In summary, this study demonstrated that the expression of mrp2 mRNA is
      regulated by PCN and 3-MC, however, bcrp mRNA expression was not significantly
      affected by PCN and 3-MC.

PMID- 16651741
TI  - Effects of perinatal stress on the emotion-related behavior of the adolescent
      mouse.
AB  - We examined the effects of perinatal stress on the emotion-related behavior of
      the mouse during their adolescent period. Firstly, we applied the sound noise
      and/or the forced swim stress to the maternal pregnant mice in the pregnant mice
      at 10 to 18 d gestation. The stress applied during the fetal period did affect
      neither the spontaneous locomotor activity of the offspring mice in a new
      environment at an age of 4 weeks, nor those sound-induced changes in the
      locomotor activity. Secondly, we applied the stress to the neonatal mouse during
      the late lactation period, 14 to 18 d after birth. The mice that underwent the
      forced swim stress accompanied by the sound noise stress showed a significant
      reduction of the locomotor activity. On the other hand, the mice that underwent
      the forced swim stress during the lactation period showed a significant increase
      in the locomotor activity after the stimulation by the sound noise. Lastly, we
      applied the stress to the neonatal mouse immediately after the weaning period, 21
      to 25 d after birth. The spontaneous locomotor activity of the mice was not
      changed compared to that of the non-stressed group. Thus, it was found that the
      stress applied to the mice during the lactation period, thought to be the
      critical period of mouse brain development, selectively influenced the emotion
      related behavior in the subsequent adolescent period. These results suggested
      that second postnatal week may be the critical period for establishing proper
      behavioral responses to emotional stress in the adolescent mouse.

PMID- 16651742
TI  - The anti-Helicobacter pylori flavones in a Brazilian plant, Hyptis fasciculata,
      and the activity of methoxyflavones.
AB  - Two known flavonoids were isolated from a tropical medicinal plant, Hyptis
      fasciculata (Labiatae), found in Brazil. Flavonoids were identified as
      cirsilineol (1) and cirsimaritin (2) by spectroscopic means and were exhibited
      potent antibacterial activity against Helicobacter pylori, and cirsilineol (1)
      had weak antibacterial activity against Escherichia coli and Salmonella
      enteritidis. Following up on the relationship between anti-H. pylori activity and
      flavonoids with methoxy groups, several methoxy flavonoids were evaluated for
      proliferation of H. pylori.

PMID- 16651743
TI  - Increased gene expression of glutathione peroxidase-3 in diabetic mouse heart.
AB  - Increased incidence of heart disease is reported in patients with diabetes. To
      elucidate a molecular profile of expressed genes during the progression of
      diabetes, a cDNA array was screened in the hearts of mice treated with
      streptozotocin (200 mg/kg, i.v.). Among the genes investigated, the plasma type
      glutathione peroxidase, GPX-3, was predominantly up-regulated in diabetic mice
      compared with control mice. In northern blot analysis, a significant increase in
      GPX-3 expression was observed as early as 5 d after the induction of
      hyperglycemia. On day 21, a nearly three-fold induction was demonstrated. Daily
      administration of insulin (0.2 U/d, s.c.) for 21 d almost completely abolished
      the increase in GPX-3 mRNA in streptozotocin-treated mice, suggesting that the
      expression level of the GPX-3 gene was dependent on insulin and serum glucose.
      Increased GPX-3 may play a significant role in protecting cardiomyocytes from
      oxidative stress caused by hyperglycemia.

PMID- 16651744
TI  - Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin
      inflammation.
AB  - Ginkgetin, a biflavonoid from Ginkgo biloba leaves (Ginkgoaceae), was previously
      demonstrated to inhibit phospholipase A2 and to suppress proinflammatory gene
      expression such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase.
      In this study, the effects of ginkgetin were examined on an animal model of
      chronic skin inflammation and proinflammatory gene expression. When topically
      applied to ICR mouse ear, ginkgetin (20-80 microg/ear/treatment) inhibited ear
      edema (22.8-30.5%) and prostaglandin E2 production (30.2-31.1%) induced by
      multiple treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 7
      consecutive days. By histological comparison, ginkgetin was also found to reduce
      epidermal hyperplasia. The expression of proinflammatory gene, interleukin-1beta,
      was suppressed by ginkgetin. From the results, it is suggested that ginkgetin may
      be beneficial against chronic skin inflammatory disorders like atopic dermatitis.

PMID- 16651745
TI  - Antimalarial activity of cassane- and norcassane-type diterpenes from Caesalpinia
      crista and their structure-activity relationship.
AB  - Malaria is one of the most life-threatening infectious diseases worldwide and
      claims millions of people's lives each year. The appearance of drug-resistance
      Plasmodium falciparum has made the treatment of malaria increasingly problematic,
      and thus, it is a dire need to search the new alternatives of current drugs. In
      the present study, 44 cassane- and norcassane-type diterpenes isolated from
      Caesalpinia crista of Myanmar and Indonesia were evaluated for their antimalarial
      activity against the malaria parasite Plasmodium falciparum FCR-3/A2 clone in
      vitro. Most of the tested diterpenes displayed antimalarial activity, and
      norcaesalpinin E (28) showed the most potent activity with an IC50 value of 0.090
      microM, more potent than the clinically used drug chloroquine (IC50, 0.29
      microM). Based on the observed results, a structure-activity relationship has
      been established.

PMID- 16651746
TI  - The cytotoxic saponin from heat-processed Achyranthes fauriei roots.
AB  - An extract of heat-processed Achyranthes fauriei roots showed more potent
      cytotoxic activity against human hepatoma SK-Hep-1 cells than that of the crude
      plant. Employing a bioassay-linked HPLC-ELSD (high performance liquid
      chromatography-evaporative light scattering detector) method, followed by silica
      gel column chromatography, a cytotoxic triterpenoid saponin, chikusetsusaponin
      IVa was isolated. It is contributive to the increased cytotoxic activity of the
      heat-processed. The amount of chikusetsusaponin IVa from the roots of Achyranthes
      fauriei was significantly increased after heat-processing.

PMID- 16651747
TI  - Alleviation of picryl chloride-induced delayed type hypersensitivity reaction by
      saponin fraction of Gleditsia sinensis.
AB  - The objective of the present study was to investigate the effects of saponin
      fraction from anomalous fruits of Gleditsia sinensis (SFGS) on picryl chloride
      induced delayed type hypersensitivity (PC-DTH) and functions of T lymphocytes and
      macrophages in mice. SFGS (100, 200 mg/kg), orally administered during either
      sensitization stage or effector stage, produced remarkable inhibition of PC-DTH.
      In vitro, SFGS (1, 2, 4 microg/ml) concentration-dependently attenuated
      concanavalin A (Con A)-elicited mouse splenocyte proliferation and interleukin 2
      (IL-2) production. At concentrations of 10 and 20 microg/ml, SFGS inhibited
      lipopolysaccharide (LPS)-induced production of nitric oxide and interleukin 1beta
      (IL-1beta) of mouse peritoneal macrophages. The findings indicate that SFGS
      attenuates PC-DTH in mice, which is probably mediated by preventing proliferation
      and differentiation of T cells during the sensitization stage and suppressing
      activation of macrophages during the effector stage.

PMID- 16651748
TI  - Poloxamer 188 and propylene glycol-based rectal suppository enhances anticancer
      effect of 5-fluorouracil in mice.
AB  - The tumoricidal and apoptosis-inducing activities of 5-fluorouracil (5-FU) have
      been demonstrated in experimental and clinical investigations. Clinically, the 5
      FU suppository form has been widely adopted for its advantages of less systemic
      toxicity, higher local tissue concentrations, and reduced first-pass effect. In
      this study, we investigated the feasibility of rectal administration of 5-FU
      suppository based on poloxamer 188 (P188) and propylene glycol (PG) and its
      anticancer effect on the murine experimental cancer models. The rectal
      suppository was made with 70% P188 and 30% PG, which was a solid phase at room
      temperature and instantly melted at physiological temperature. The treatment with
      the 5-FU suppository was more effective than the oral route in decreasing the
      volume of rectal cancer in mice. In addition, the survival rate of the mice with
      rectal cancer was higher in the group treated with the 5-FU suppository than in
      the group treated with 5-FU orally. Furthermore, in mice skin cancers induced by
      inoculation of murine CT-26 colon carcinoma cells, the anticancer effect of 5-FU
      was significantly enhanced by the rectal administration of the suppository than
      by oral treatment. Taken together, the results suggest that a poloxamer gel
      system with 5-FU/P188/PG is an effective rectal dosage form for the treatment of
      both rectal and non-rectal cancers.

PMID- 16651749
TI  - Effect of 2-methoxyestradiol, buthionine sulfoximine and hydrogen peroxide on the
      viability of renal carcinoma cell lines (ACHN and ACVB).
AB  - 2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, induces
      the intracellular accumulation of superoxide anion (O2*-) and buthionine
      sulfoximine (BSO) is an inhibitor of glutathione (GSH) synthesis. We have
      examined the combination anticancer effect of 2-ME and BSO accompanied with
      hydrogen peroxide (H2O2). 2-ME inhibited cell growth in renal carcinoma cell
      lines (ACHN and ACVB) accompanied by an increase in the intracellular contents of
      GSH. The combination of 2-ME, BSO and H2O2 showed a significant antiproliferation
      effect in both ACHN and ACVB. The intracellular levels of reactive oxygen species
      (ROS) with a combination with 2-ME and H2O2 in ACHN and ACVB pretreated with BSO
      were markedly increased, which may have contributed to the potential
      antiproliferative action.

PMID- 16651750
TI  - Comparison of nicotine pharmacokinetics in healthy Japanese male smokers
      following application of the transdermal nicotine patch and cigarette smoking.
AB  - Transdermal nicotine patch (TNP) contains approximately 16.6 and 24.9 mg of
      nicotine per 20 and 30 cm2 (TNP-20 and TNP-30). The aims of the study are to
      investigate linearity of nicotine pharmacokinetics after single application of
      different strengths of TNP and to directly compare plasma nicotine concentrations
      with those during cigarette smoking. Twelve healthy Japanese male smokers were
      randomly allocated to 1 of 2 cohorts consisting of 6 subjects each. Cohort 1
      subjects received 1 sheet of TNP-20 (TNP-20x1) in period 1, and 2 sheets of TNP
      20 (TNP-20x2) in period 3. Cohort 2 subjects were received 1 sheet of TNP-30 (TNP
      30x1) in period 2, and smoked a total of 12 cigarettes at 1 h intervals in period
      4. Each TNP was applied to the upper arm for 16 h. After TNP-20x1 or TNP-20x2
      treatment in cohort 1, the amount of nicotine delivered from TNP (Dose) was
      proportional to surface area of TNP. Cmax and AUC of nicotine increased with the
      surface area (Dose), and tmax, t(1/2), CL/F and percentage of dose excreted in
      urine were almost the same between both treatments. These suggest the linear
      pharmacokinetics of nicotine in proportion to the surface area and Dose following
      single application of TNP in identical subjects. In cohort 2, the plasma nicotine
      concentrations after TNP-30x1 treatment were approximately half those just before
      each smoking.

PMID- 16651751
TI  - Triterpenoid saponins from the fruits of Akebiae quinata.
AB  - Three new triterpenoid saponins together with eight known compounds have been
      isolated from the fruits of Akebiae quinata. On the basis of the spectroscopic
      and physiochemical evidence, the new compounds were elucidated as 3-O-beta-D
      xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl gypsogenin, 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl gypsogenin and 3-O-beta-D
      xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-28-O-beta-D-glucopyranosyl-(1-->6)
      beta-D-glucopyranosyl gypsogenin.

PMID- 16651752
TI  - Study of the critical points in lobenzarit disodium hydrophilic matrices for
      controlled drug delivery.
AB  - Percolation theory is a multidisciplinary theory that studies chaotic systems. It
      has been applied in the pharmaceutical field since 1987. The application of this
      theory to study the release and hydration rate of hydrophilic matrices allowed
      for first time to explain the changes in release and hydration kinetic of
      swellable matrices type controlled delivery systems. The objective of the present
      paper is to estimate the percolation threshold of HPMC K4M in matrices of
      lobenzarit disodium and to apply the obtained result to the design of hydrophilic
      matrices for the controlled delivery of this drug. The materials used to prepare
      the tablets were Lobenzarit disodium (LBD) and HPMC of viscosity grade K4M. The
      drug mean particle size was 42+/-0.61 mum and the polymer was sieved and 150-200
      microm granulometric fraction was selected. The formulations studied were
      prepared with different excipient contents in the range of 10-80% w/w.
      Dissolution studies were carried out using the paddle method and the water uptake
      measurements were performed using a modified Enslin apparatus. In order to
      estimate the percolation threshold, the behaviour of the kinetic parameters with
      respect to the volumetric fraction of each component at time zero, was studied.
      According to percolation theory, the critical points observed in dissolution and
      water uptake studies are attributed to the existence of an excipient percolation
      threshold. This threshold was situated between (18.58 to 24.33% v/v of HPMC).
      Therefore, the LBD-HPMC K4M matrices with a relative HPMC particle size of should
      be formulated with an excipient content above 24.33% v/v of HPMC, to obtain a
      control of the drug release from these systems.

PMID- 16651753
TI  - A novel dual antagonist of thromboxane A2 and leukotriene D4 receptors: synthesis
      and structure-activity relationships of chloroquinolylvinyl derivatives.
AB  - To discover an orally active thromboxane A(2) (TXA(2)) and leukotriene D(4)
      (LTD(4)) dual antagonist, we designed and synthesized chloroquinolylvinyl
      derivatives based on the structures of the TXA(2) antagonist daltroban and the
      LTD(4) antagonist montelukast. Among these derivatives, 4-{[(2-(4
      chlorophenylsulfonylamino)-1-{3-[(E)-2-(7-chloro-2
      quinolyl)vinyl]phenyl}ethyl)thio]methyl}benzoic acid (18d) showed potent
      inhibitory activity against U46619-induced aggregation of guinea pig platelets
      and LTD(4)-induced contraction in the guinea pig ileum, with IC(50) values of 340
      nm and 0.40 nm, respectively. Oral administration of 18 d also inhibited both the
      LTD(4)-induced acceleration of plasma leakage to skin in guinea pig and the
      U46619-induced increase in airway resistance in guinea pig with ED(50) values of
      0.47 mg/kg and 3.3 mg/kg, respectively.

PMID- 16651754
TI  - Synthesis and evaluation as NOP ligands of some spiro[piperidine-4,2'(1'H)
      quinazolin]-4'(3'H)-ones and spiro[piperidine-4,5'(6'H)-[1,2,4]triazolo[1,5
      c]quinazolines].
AB  - Some spiro[piperidine-4,2'(1'H)-quinazolin]-4'(3'H)-ones 3 and spiro[piperidine
      4,5'(6'H)-[1,2,4]triazolo[1,5-c]quinazolines] 4 were synthesized and evaluated as
      ligands of the nociceptin receptor. The examined compounds showed partial
      agonistic activity, except compounds 3, 4n that proved to be pure antagonists.

PMID- 16651755
TI  - Halosterols A and B, chymotrypsin inhibitory sterols from Haloxylon recurvum.
AB  - Two new sterols, halosterols A (1) and B (2), have been isolated from the CHCl(3)
      soluble fraction of Haloxylon recurvum, and their structures were elucidated by
      spectroscopic techniques including two dimensional-NMR. Both the compounds
      displayed chymotrypsin enzyme inhibitory potential.

PMID- 16651756
TI  - Quantitative analysis of irbesartan in commercial dosage forms by kinetic
      spectrophotometry.
AB  - The objective of this work is to develop a new kinetic spectrophotometric method
      for the determination of irbesartan in pharmaceutical formulations. The method is
      based on the reaction of carboxylic acid group of the oxidized irbesartan with a
      mixture of potassium iodate (KIO(3)) and iodide (KI) to form yellow colored
      triiodide ions in aqueous medium at 30+/-1 degrees C. The reaction is followed
      spectrophotometrically by measuring the rate of change of absorbance at 352 nm.
      The initial-rate and fixed-time (DeltaA) methods are adopted for constructing the
      calibration curves, which were found to be linear over the concentration ranges
      of 10.0-60.0 and 7.5-60.0 microg ml(-1) respectively. The regression analysis of
      calibration data yielded the linear equations: rate=-2.138 x 10(-6)+1.058 x 10(
      4)C and DeltaA=-3.75 x 10(-3)+3.25 x 10(-3)C for initial rate and fixed time
      (DeltaA) methods, respectively. The limit of detection for initial rate and fixed
      time methods are 0.21 and 2.40 mug ml(-1), respectively. The various activation
      parameters such as E(a), DeltaH++, DeltaS++ and DeltaG++ are also calculated for
      the reaction and found to be 70.95+/-0.43 kJ mol(-1), 68.48+/-0.21 kJ mol(-1),
      16.54+/-0.24 J K(-1) mol(-1) and -4.94+/-0.07 kJ mol(-1), respectively. The
      proposed methods are optimized and validated as per the guidelines of
      International Conference on Harmonisation (U.S.A.). The point and interval
      hypothesis tests have been performed which indicate that there is no significant
      difference between the proposed methods and the reference method. The methods
      have been successfully applied to the determination of irbesartan in commercial
      dosage forms.

PMID- 16651757
TI  - Novel penicillins synthesized by biotransformation using laccase from Trametes
      spec.
AB  - Eight novel penicillins were synthesized by heteromolecular reaction of
      ampicillin or amoxicillin with 2,5-dihydroxybenzoic acid derivatives using a
      laccase from Trametes spec. All products inhibited the growth of several gram
      positive bacterial strains in the agar diffusion assay, among them methicillin
      resistant Staphylococcus aureus and vancomycin-resistant Enterococci. The
      products protected mice against an infection with Staphylococcus aureus lethal to
      the untreated animals. Cytotoxicity and acute toxicity of the new compounds were
      neglectable. The results show the usefulness of laccase for the synthesis of
      potential new antibiotics. The biological activity of the new compounds
      stimulates intensified pharmacological tests.

PMID- 16651758
TI  - Synthesis and biological properties of gemini quaternary ammonium compounds, 5,5'
      [2,2'-(alpha,omega-polymethylnedicarbonyldioxy)diethyl]bis-(3-alkyl-4
      methylthiazolium iodide) and 5,5'-[2,2'-(p-phenylenedicarbonyldioxy)diethyl]bis(3
      alkyl-4-methylthiazolium bromide).
AB  - We synthesized gemini quaternary ammonium compounds (gemini QACs) having two
      thiazolium moieties in a molecule, 5,5'-[2,2'-(alpha,omega
      polymethylnedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium iodide) (5DEBT
      m,n), on which the carbon number of the methylene chain linking the two thiazoles
      (m) is 2, 6 or 8 and that of the alkyl group (n) is 8, 10, 12, 14 or 16. 5,5'
      [2,2'-(p-Phenylenedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium bromide)
      (5DEBT-P,n) was then synthesized, which is composed of a p-phenylene as the
      methylene spacer. For five gemini QAC series, in addition to the previously
      described 5DEBT-4,n to the four new compound series, their antimicrobial
      activities were determined. 5DEBT-m,10 and -P,10 exhibited a wide and strong
      bacteriostatic activity against gram-negative and -positive bacteria, fungi and
      then yeast in comparison with N-tetradecyl-5-(2-hydroxyethyl)-4-methylthiazolium
      iodide as a mono-QAC. The bactericidal activity of the 5DEBT series against
      Escherichia coli IFO 12713 and Staphylococcus aureus IFO 12732 was investigated
      on the basis of the effects of their alkyl chain length and their molecular
      hydrophobicity. It was found that the effect of theses factors on their activity
      significantly changes by the difference between the gram-negative and -positive
      bacteria. Although against the gram-negative bacterium, the change in the
      activity due to extension of the alkyl group for each compound affected the kind
      of methylene spacer, against the gram-positive bacterium, it was almost equal in
      spite of the methylene spacer. This result could be responsible for the
      bactericidal mechanism of the gemini QACs being influenced by the diversity of
      the steric structure participating in the methylene chain length and by the
      bacterium cell surface hydrophobicity.

PMID- 16651759
TI  - Improved CNDO/S calculation of electronic spectra of organic compounds. I. New
      CNDO/S calculation by using an improved method of one-center electron repulsion
      integral.
AB  - The NM-gamma CNDO/S program previously developed by our group was modified by the
      introduction of a new one-center electron repulsion integral gamma(AA)(new)
      approximation, namely, the gamma(AA)(new)-CNDO/S method. The value of this
      gamma(AA)(new) was evaluated according to the product values of the coefficient C
      with the gamma(AA) value proposed in our previous paper. This method using a new
      gamma(AA) was also found to improve the two-center electron repulsion integral
      gamma(AB) value with respect to the chemical softness proposed by Nishimoto and
      co-workers, together with the difference between HOMO and LUMO orbital energies.
      The results calculated by the present improved gamma(AA)(new)-CNDO/S method
      demonstrated that not only the calculated absorption maxima wavelengths and
      ionization potentials, but also the order and the assignment of orbitals
      coincided very well with those based on the results of experiments investigating
      a variety of polyenes, cyanynes, and polycyclic aromatic hydrocarbons.

PMID- 16651760
TI  - Spectrofluorimetric and spectrophotometric stability-indicating methods for
      determination of some oxicams using 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD
      Cl).
AB  - Two sensitive and selective spectrofluorimetric and spectrophotometric stability
      indicating methods have been developed for the determination of some non
      steroidal anti-inflammatory oxicam derivatives namely lornoxicam (Lx), tenoxicam
      (Tx) and meloxicam (Mx) after their complete alkaline hydrolysis. The methods are
      based on derivatization of alkaline hydrolytic products with 7-chloro-4-nitrobenz
      2-oxa-1,3-diazole (NBD-Cl). The products showed an absorption maximum at 460 nm
      for the three studied drugs and fluorescence emission peak at 535 nm in methanol.
      The color was stable for at least 48 h. The optimum conditions of the reaction
      were investigated and it was found that the reaction proceeds quantitatively at
      pH 8, after heating in a boiling water bath for 30 min. The methods were found to
      be linear in the ranges of 1-10 microg ml(-1) for Lx and Tx and 0.5-4.0 microg
      ml(-1) for Mx for spectrophotometric method, while 0.05-1.0 microg ml(-1) for Lx
      and Tx and 0.025-0.4 microg ml(-1) for Mx for the spectrofluorimetric method. The
      validity of the methods was assessed according to USP guidelines. Statistical
      analysis of the results revealed high accuracy and good precision. The suggested
      procedures could be used for the determination of the above mentioned drugs in
      pure and dosage forms as well as in the presence of their degradation products.

PMID- 16651761
TI  - Structure-activity relationships of neuromedin U. V. study on the stability of
      porcine neuromedin U-8 at the C-terminal asparagine amide under mild alkaline and
      acidic conditions.
AB  - Porcine neuromedin U-8 (X-Asn-NH(2), X=H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg) is
      occasionally unstable in the biological fluids used for bioassay as well as in
      the acidic solutions used for purification of synthetic peptides. In this study,
      HPLC examination of an incubate solution of X-Asn-NH(2) revealed that the main
      decomposition products in Tyrode's solution (pH 7.4) were either alpha- or beta
      monocarboxylic acid analogs (X-Asn-OH or X-Asp-NH(2)), and that no dicarboxylic
      acid analog (X-Asp-OH) was produced. Further investigation, employing a model
      peptide (Y-Asn-NH(2), Y=Benzoyl-Pro-Arg) incubated in a 0.1 M sodium bicarbonate
      solution at 60 degrees C, revealed that the decomposition of C-terminal Asn-NH(2)
      occurred through the formation of an aminosuccinimide intermediate (Y-Asu), at a
      rate faster than that of Y-Asn-Ser peptide but slower than that of Y-Asn-Gly
      peptide. Mild acid hydrolysis of X-Asn-NH(2) examined in a 1 M HCl solution at 60
      degrees C yielded X-Asn-OH and X-Asp-NH(2), which further decomposed to yield X
      Asp-OH. The C-terminal degradation of X-Asn-NH(2) resulted in reduced biological
      and immunochemical binding activities.

PMID- 16651762
TI  - Stereoselective conversion of anhydrovinblastine into vinblastine utilizing an
      anti-vinblastine monoclonal antibody as a chiral mould.
AB  - Dimeric indole alkaloid, anhydrovinblastine, which can be obtained from
      catharanthine and vindoline in a high yield, was converted stereoselectively into
      vinblastine through alternating oxidation-reduction with oxygen and NaBH(3)CN in
      the presence of anti-vinblastine monoclonal antibody.

PMID- 16651763
TI  - Monoterpene constituents from Cistanche tubulosa--chemical structures of
      kankanosides A-E and kankanol-.
AB  - Four new iridoid glycosides, kankanosides A (1), B (2), C (3), and D (4), a
      chlorinated iridoid, kankanol (5), and an acyclic monoterpene glycoside,
      kankanoside E (6), were isolated from the methanolic extract of dried stems of
      Cistanche tubulosa (SCHRENK) R. WIGHT (Orobanchaceae) together with 16 known
      compounds. The structures of these new compounds (1-6) were determined on the
      basis of the chemical and physicochemical evidence.

PMID- 16651764
TI  - A new eudesmane derivative and a new fatty acid ester from Sambucus williamsii.
AB  - 1,4,13-Trihydroxy-eudesm-11(12)-ene, a new eudesmane derivative (3), (9E)-8,11,12
      trihydroxyoctadecenoic acid methyl ester, a new fatty acid ester (2) and tianshic
      acid (1) were obtained from the stems of Sambucus williamsii. Their structures
      were elucidated by physiochemical properties and spectroscopic analysis. Both
      compounds 1 and 2 showed stimulating effects on alkaline phosphatase activity of
      the osteoblastic UMR106 cell about 1.5 fold at 30 mumol/l while they had no
      effects on cell proliferation.

PMID- 16651765
TI  - Antimicrobial C-glucoside from aerial parts of Diospyros nigra.
AB  - A new C-alkylglucoside, diospyrodin [beta-1C-(1'S*,2'R*,3'R*,4'S*-1',2',3',4',5'
      pentahydroxypentyl)-glucopyranoside] (1) has been isolated as its nonaacetate
      from the leaves and stems of Diospyros nigra. Its structure was elucidated on the
      basis of chemical and spectral properties and a single crystal X-ray analysis. It
      showed antimicrobial activity against Gram-positive and Gram-negative bacteria.

PMID- 16651766
TI  - HIV-1 integrase inhibition of biscoumarin analogues.
AB  - Nineteen biscoumarins bearing free and modified hydroxyl substituents at
      benzoyloxyphenyl linker have been synthesized by multiple step synthesis. Among
      these biscoumarins, thirteen were found to be active molecules against HIV-1
      integrase (HIV-1 IN). The structure-activity relationship of the nineteen
      compounds on HIV IN may be useful for the design of potent therapeutic agents.

PMID- 16651767
TI  - The quantification of monacolin K in some red yeast rice from Fujian province and
      the comparison of the other product.
AB  - When used as a dietary supplement to achieve and maintain healthy cholesterol
      levels,Chinese red yeast rice has significant potential to reduce health care
      costs and contribute to public health by reducing heart disease risk in
      individuals with moderate elevations of circulating cholesterol levels. Red yeast
      rice is typical product in Mingbei area of Fujian province. Nine products from
      different area were measured, using high-performance chromatography (HPLC) with
      photodiode array detector (PDA) and tandem mass spectrometry (MS) and the results
      show that the contents of monacolin K in these products were considerably
      different, and more than the other product.

PMID- 16651768
TI  - Cyclic peptides from the seeds of Annona glauca and A. cherimola.
AB  - From the seeds of Annona glauca and A. cherimola, two novel cyclic peptides,
      glaucacyclopeptide B and cherimolacyclopeptide G, have been isolated,
      respectively. Their structures were elucidated by chemical and spectral methods.

PMID- 16651769
TI  - New constituents from the heartwood of Picea morrisonicola HAYATA.
AB  - Three new constituents, including a p-menthane type monoterpene, trans-p-menthane
      7,8,9-triol (1), an aromatic, 2,6-dihydroxy-3,4-dimethylbenzoic acid methyl ester
      (2), and a lignan, (+)-morrisonicolanin (3), were isolated from the low polar
      layer of heartwood extracts of Picea morrisonicola, and their structures were
      elucidated on the basis of spectroscopic analysis. Of these compounds identified,
      1 was obtained as its diacetylated derivative 1a, and 2 was the chemical entity
      first isolated from a natural source.

PMID- 16651770
TI  - Two new C21 steroidal glycosides from Marsdenia tenacissima (ROXB.) WIGHT et ARN.
AB  - Two new C(21) steroidal glycosides, tenacissoside L (1), tenacissoside M (2),
      were isolated from the stems of Marsdenia tenacissima (ROXB.) WIGHT et ARN. Their
      structures were elucidated, respectively, by means of chemical and spectral data,
      including ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR.

PMID- 16651771
TI  - Carbonylative cross-coupling reaction of ethynylstibane with aryl iodides.
AB  - Palladium-catalyzed carbonylative cross-coupling reaction of ethynylstibane
      (PhSbPh(2)) and aryl iodides (Ar-I) is described. The reaction of the stibanes
      and the halides under 1 atm of carbon monoxide in N,N-dimethylacetamide using a
      combination of 5 mol% Pd(OAc)(2) and 4 equivalents (20 mol%) of PPh(3) brought
      about carbonylative cross-coupling reaction to afford arylethynylketones
      [ArC(O)Ph] in good yields along with a small amount of directly coupled products,
      aryl acetylens (ArPh). Formation of the side product was completely suppressed by
      conducting the reaction under high CO pressure (20 atm) conditions. The present
      method provides a variety of carbonylated products in good yield even with
      electron-deficient aryl iodides which usually give inferior results due to their
      tendency to undergo decarbonylation in the cross-coupling reaction of
      ethynylstibanes and acyl halides.

PMID- 16651772
TI  - Effective preparation of cycloheptimidazol-4-one compounds.
AB  - Effective preparation of cycloheptimidazol-4-ones was developed. The reactions of
      2-tosyloxytropone (5) with amidines (6) carried out under simple conditions such
      as aq. NaOH in toluene at 35 degrees C afforded the corresponding
      cycloheptimidazol-4-ones (3) in low yield. However, by adding tetra-n
      butylammonium bromide (n-Bu(4)NBr) to this reaction system, the yield was
      improved dramatically. The reaction conditions were screened in detail.

PMID- 16651773
TI  - Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3h-cycloheptimidazol-4
      ones and 2-alkyl-3h-cycloheptimidazol-4-ones.
AB  - Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4
      one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2'-(1
      tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H
      cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by
      using NaH in DMF or THF. On the other hand, 3-[2'-(1-tert-butyl-1H-tetrazol-5
      yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one
      (5), the synthetic intermediate compound of Pratosartan, was obtained selectively
      in the presence of n-Bu(4)NBr in toluene by using aqueous sodium hydroxide as a
      base. In this reaction, it was found that the concentration of the alkaline
      solution influences its regioselectivity. This selectivity was observed even for
      aldehyde and ester derivatives.

PMID- 16651774
TI  - PARAFAC and PLS applied to spectrophotometric determination of tetracycline in
      pharmaceutical formulation and biological fluids.
AB  - A simple and rapid analytical procedure was proposed for determination of
      tetracycline in pharmaceutical formulation, urine and plasma based on
      chemometrics methods and spectrophotometric measurements. The calibration set was
      constructed with twenty solutions in concentration range 0.25-13.00 microg ml(-1)
      for tetracycline. The procedure was repeated at nine different pH values. Partial
      least squares (PLS) models were built at each pH and used to determinate a set of
      synthetic tetracycline solutions. The best model was obtained at pH 8.00 (PLS
      PH8). Parallel factor analysis (PARAFAC) model was applied to a three-way array
      constructed using all the pH data sets and enabled better results. The
      capabilities of the method for the analysis of real samples were evaluated by
      determination of tetracycline in pharmaceutical formulations and biological
      fluids with satisfactory results.

PMID- 16651775
TI  - Psoralenoside and isopsoralenoside, two new benzofuran glycosides from Psoralea
      corylifolia.
AB  - Two new benzofuran glycosides, called psoralenoside and isopsoralenoside, were
      isolated from the fruits of Psoralea corylifolia, together with nine known
      compounds. Their structures were elucidated by detailed spectral analyses
      including extensive two dimensional (2D) NMR spectra.

PMID- 16651776
TI  - Two isocoumarins from Pleurospermum angelicoides.
AB  - Two new isocoumarins, angelicoins A and B, were isolated from the roots of
      Pleurospermum angelicoides, and their structures were established by spectral
      means.

PMID- 16651777
TI  - Biotransformation of isoflavones by the larvae of the common cutworm (Spodoptera
      litura).
AB  - Biotransformation of the 5,7,4'-trimethoxyisoflavone (1), 6,7,4'
      trimethoxyisoflavone (2), and 7,4'-dimethoxyisoflavone (3) by insects, Spodoptera
      litura was investigated. Compound 1 was transformed to 5-hydroxy-7,4'
      dimethoxyisoflavone (4), 7-hydroxy-5,4'-dimethoxyisoflavone (5) and 4'-hydroxy
      5,7-dimethoxyisoflavone (6) by S. litura. Compounds 2 and 3 were hardly
      metabolized by S. litura. This suggested that compound 1 was converted to
      compounds 4, 5 and 6 by demethylation at the C-5, C-7 and C-4' position,
      respectively.

PMID- 16651778
TI  - Puqienine F, a novel veratramine alkaloid from the bulbs of Fritillaria
      puqiensis.
AB  - A novel veratramine alkaloid, called puqienine F (1) and possessing a 12,16-epoxy
      ring, was isolated from the bulbs of Fritillaria puqiensis G. D. Yu et G. Y. Chen
      (Liliaceae). The structure was elucidated by extensive spectral and X-ray
      crystallographic analyses.

PMID- 16651779
TI  - Tentative fingerprint-efficacy study of Houttuynia cordata injection in quality
      control of traditional Chinese medicine.
AB  - To establish potent fingerprint for quality control of traditional Chinese
      medicine, Houttuynia cordata (Saururaceae) injection (HCI), the attempt on
      fingerprint-efficacy was developed in this study. HCI from ten different
      factories were determined by gas chromatography-mass spectrum (GC-MS) and
      classified by hierarchical clustering. The anti-inflammatory effect of HCI was
      characterized with the rat pleurisy model induced by carrageenin and the mice ear
      edema model by xylene. The results showed that anti-inflammatory effect of the
      injections from most of factories on the two models was significant. There was
      corresponding relationship between the fingerprint of HCI and efficacy to certain
      extent. The main common constitutes in injection from the factories that possess
      anti-inflammatory activity were analysed with GC-MS and identified using the NIST
      Mass Spectral Database. This common pattern of HCI based on the efficacy was
      helpful for the purpose of quality control.

PMID- 16651780
TI  - Ab initio molecular orbital study of the reactivity of active alkyl groups. VII.
      Solvent effects on the formation of enolate isomers from 2-butanone with
      methoxide anion in methanol.
AB  - The mechanism of the deprotonation of 2-butanone (1) with methoxide anion (2) was
      studied by ab initio molecular orbital (MO) methods. Calculations of the
      thermodynamic stabilities of each complex and the regioselectivity of the
      reaction were performed using a static isodensity surface polarized continuum
      model (IPCM) which takes the solvent effect into consideration. The calculated
      energies of the complexes lead ultimately to the conclusion that the major
      deprotonation pathway in protic solvents is dependent upon thermodynamically
      stable complexes with small activation energies under equilibrium control.

PMID- 16651781
TI  - Acerogenin M, a cyclic diarylheptanoid, and other phenolic compounds from Acer
      nikoense and their anti-inflammatory and anti-tumor-promoting effects.
AB  - A new cyclic diarylheptanoid, acerogenin M (1), has been isolated along with nine
      known diarylheptanoids, 2-10, and two known phenolic compounds, 11 and 12, from a
      MeOH extract of the stem bark of Acer nikoense MAXIM. (Aceraceae). The structure
      of 1 was determined on the basis of a spectroscopic method. Upon evaluation of
      the inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inflammation (1 microg/ear) in mice of nine of the compounds (2-6, 8, 10-12), six
      (2, 4-6, 8, 10) showed a marked anti-inflammatory effect with a 50% inhibitory
      dose (ID(50)) of 0.26-0.81 mg per ear. In addition, upon an evaluation against
      the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA for all
      of the compounds, all exhibited moderate inhibitory effects against EBV-EA
      induction (IC(50) values of 356-534 mol ratio/32 pmol TPA).

PMID- 16651782
TI  - Three new pentacyclic triterpenes and some flavonoids from the fruits of an
      Indian Ayurvedic plant Dendrophthoe falcata and their estrogen receptor binding
      activity.
AB  - Extensive chromatographic screening of extracts of the fruits of the Indian
      Ayurvedic plant, Dendrophthoe falcata, resulted in the isolation of three new
      triterpenes, 3beta-acetoxy-1beta-(2-hydroxy-2-propoxy)-11alpha-hydroxy-olean-12
      ene (1), 3beta-acetoxy-11alpha-ethoxy-1beta-hydroxy-olean-12-ene (2) and 3beta
      acetoxy-1beta-hydroxy-11alpha-methoxy-olean-12-ene (3) along with nine known
      compounds, 3beta-acetoxy-1beta,11alpha-dihydroxy-olean-12-ene (4), 3beta-acetoxy
      1beta,11alpha-dihydroxy-urs-12-ene (5), 3beta-acetoxy-urs-12-ene-11-one (6),
      3beta-acetoxy-lup-20(29)-ene (7), 30-nor-lup-3beta-acetoxy-20-one (8), (20S)
      3beta-acetoxy-lupan-29-oic acid (9), kaempferol-3-O-alpha-L-rhamnopyranoside
      (10), quercetin-3-O-alpha-L-rhamnopyranoside (11), and gallic acid (12). The
      structures of these compounds were determined using 1D and 2D NMR and high
      resolution electrospray mass spectrometry. These compounds were assayed for
      binding to estrogen receptors-alpha and beta and kaempferol-3-O-alpha-L
      rhamnopyranoside (10) was found to be a ligand for both receptors with greater
      affinity for beta. The triterpenes (1-9) are reported for the first time in the
      genus Dendrophthoe and assumes taxonomic significance.

PMID- 16651783
TI  - Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense.
AB  - A new prenylated xanthone, 5-O-methylcelebixanthone (1), together with six known
      compounds; celebixanthone (2), 1,3,7-trihydroxy-2,4-di(3-methylbut-2
      enyl)xanthone (3), cochinchinone A (4), alpha-mangostin (5), beta-mangostin (6)
      and cochinchinone C (7) were isolated from roots of Cratoxylum cochinchinense.
      Their structures were elucidated by spectroscopic methods. Compounds 2 and 4-7
      showed cytotoxic activity against the human lung cancer cell line (NCI-H187) with
      IC(50) values ranging from 0.65 to 5.2 microg/ml. Compounds 1, 2, 6 and 7 also
      showed antimalarial activity against Plasmodium falciparum with IC(50) values of
      3.2, 4.9, 7.2 and 2.6 microg/ml, respectively.

PMID- 16651784
TI  - Phenolic constituents from the rhizomes of Dryopteris crassirhizoma.
AB  - A new phenolic glycoside, dryopteroside (1), was isolated from the rhizomes of
      Dryopteris crassirhizoma (Dryopteridaceae), together with five known compounds,
      4beta-carboxymethyl-(-)-epicatechin (2), isobiflorin (3), biflorin (4), 1-beta-D
      glucopyranosyloxy-3-methoxy-5-hydroxybenzene (5) and (+)-catechin-6-C-beta-D
      glucopyranoside (6). The new compound was elucidated to be 1-butanoyl-3-C-beta-D
      glucopyranosyl-5-methyl-phloroglucinyl-6-O-beta-D-glucopyranoside (1) by chemical
      and various spectroscopic analyses. The known compounds 2-6 were first reported
      from the genus Dryopteris.

PMID- 16651785
TI  - Ginsenoside Rg8, a new dammarane-type triterpenoid saponin from roots of Panax
      quinquefolium.
AB  - A new dammarane-type triterpenoid saponin, ginsenoside Rg(8) (1), was isolated
      from the roots of Panax quinquefolium, along with five known saponins, (20E)
      ginsenoside F(4) (2), ginsenosides Rh(1) (3), Rg(2) (4), F(1) (5), and (20R)
      ginsenoside Rh(1) (6). The structure of ginsenoside Rg(8) (1) was determined to
      be (3beta,6alpha,12beta,20E)-24,25-epoxy-3,12,23-trihydroxydammar-20(22)-en-6-O
      alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside by various spectroscopic
      analyses. Among the known saponins, (20E)-ginsenoside F(4) (2) and ginsenoside
      F(1) (5) were first reported from the title plant.

PMID- 16651786
TI  - Quantitative determination of jatrophone in "cachaca" prepared with Jatropha
      elliptica.
AB  - A method for sample preparation and analysis by high performance liquid
      chromatography with UV detection (HPLC-UV) was developed for analysis of
      jatrophone in "cachaca" prepared with Jatropha elliptica, administered orally,
      employed in Brazil for the treatment of venomous snake bites. The linearity,
      accuracy, precision of the procedure was evaluated. Analytical curve for
      jatrophone was linear in the range of 16.24-81.20 microg ml(-1). The recovery of
      the jatrophone in the samples analyzed was 98.99-99.89%. The percent coefficient
      of variation for the quantitative analysis of the "cachaca" in the analyses was
      under 2%.

PMID- 16651787
TI  - Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of
      aphidicolin-like tetracyclic diterpene of Scoparia dulcis.
AB  - Specific inhibitors of the MVA pathway (pravastatin) and the MEP pathway
      (fosmidomycin) were used to interfere with the biosynthetic flux which leads to
      the production of aphidicolin-like diterpene in leaf organ cultures of Scoparia
      dulcis. Treatment of leaf organs with fosmidomycin resulted in dose dependent
      inhibition of chlorophylls, carotenoids, scopadulcic acid B (SDB) and phytol
      production, and no effect on sterol production was observed. In response to the
      pravastatin treatment, a significant decrease in sterol and perturbation of SDB
      production was observed.

PMID- 16651788
TI  - Development of soft-based double-stranded peptide chelators which selectively
      separate europium and lanthanum ions based on the hardness concept.
AB  - New double-stranded peptide chelators (1) conjugated Cat (2,3-dihydroxybenzoic
      acid) were synthesized and formed a molecular complex 1-Eu(3+) (or 1-Lu(3+)) with
      Eu(3+) and Lu(3+) but not La(3+). The double-stranded peptide chelator may prove
      to be useful tools for studying the selective separation of lanthanide ions.

PMID- 16651789
TI  - [TRP channels and nociception].

PMID- 16651790
TI  - [Proteinase-activated receptor-2 and pain].

PMID- 16651791
TI  - [Neurogenic inflammation facilitates neuropeptides release from primary afferent
      neurons].

PMID- 16651792
TI  - [Production of nitric oxide in the spinal cord and pain].

PMID- 16651793
TI  - [Cognitive neuroscience and neuropharmacology of itching in humans].

PMID- 16651794
TI  - [Animal models of neuropathic pain].

PMID- 16651795
TI  - [Ca channel and pain transmission].

PMID- 16651796
TI  - [Lysophosphatidic acid as initiator of neuropathic pain].

PMID- 16651797
TI  - [ATP receptors in pain].

PMID- 16651798
TI  - [Clinical approach to cancer pain].

PMID- 16651799
TI  - [The prevalence of chronic pain in Japan].

PMID- 16651800
TI  - [Cigarette smoke-induced animal models to evaluate drug efficacy on chronic
      obstructive pulmonary disease (COPD)].

PMID- 16651801
TI  - [Finding a novel target for depression through the orphan receptor strategy].

PMID- 16651802
TI  - [Neuropeptide receptors: novel therapeutic targets for depression].

PMID- 16651803
TI  - [Depression and BDNF].

PMID- 16651804
TI  - [Clinical development of antidepressants].

PMID- 16651805
TI  - [The problems of the current antidepressants and their future possibilities].

PMID- 16651806
TI  - [Physicochemical profiling and preformulation studies at the drug discovery
      stage].

PMID- 16651807
TI  - [Safety, pharmacokinetic, and physicochemical studies in the early stage of drug
      discovery].

PMID- 16651808
TI  - [Pharmacokinetic, pharmacological, and clinical profile of miglitol (SEIBULE), a
      novel alpha-glucosidase inhibitor].

PMID- 16651809
TI  - Targets of cytoprotection in acute ischemic stroke: present and future.
AB  - Although the management of stroke has improved remarkably over the last decade
      due mainly to the advent of thrombolysis, most neuroprotective agents, although
      successful in animal studies, have failed in humans. Our increasing knowledge
      concerning the ischemic cascade is leading to a considerable development of
      pharmacological tools suggesting that each step of this cascade might be a target
      for cytoprotection. Glutamate has long been recognized to play key roles in the
      pathophysiology of ischemia. However, although some trials are still ongoing, the
      results from several completed trials with drugs interfering with the
      glutamatergic pathway have been disappointing. Regarding the inhibition of
      glutamate release as a possible target for cytoprotection, it might be afforded
      either by decreasing glutamate efflux or by increasing glutamate uptake. In this
      context, it has been shown that glutamate transport is the primary and only
      mechanism for maintaining extracellular glutamate concentrations below
      excitotoxic levels. This transport is executed by the five high-affinity, sodium
      dependent plasma membrane glutamate transporters. Among them, the transporter
      EAAT2 is responsible for up to 90% of all glutamate transport. We will discuss
      the effect of different neuroprotective tools (membrane stabilizers or endogenous
      neuroprotection) affecting glutamate efflux and/or expression of EAAT2. We will
      also describe the finding of a novel polymorphism in the EAAT2 promoter region
      which could be responsible for differences in both gene function and regulation
      under pathological conditions such as cerebral ischemia, and which might well
      account for the failure of glutamate antagonists in the clinical practice. These
      results may possess important therapeutic implications in the management of
      patients at risk of ischemic events, since it has been demonstrated that those
      patients with progressing stroke have higher plasma concentrations of glutamate
      which remain elevated up to 24 h when compared to the levels in patients without
      neurological deterioration.

PMID- 16651810
TI  - Apoptosis: future targets for neuroprotective strategies.
AB  - Focal permanent or transient cerebral artery occlusion produces massive cell
      death in the central core of the infarction, whereas in the peripheral zone
      (penumbra) nerve cells are subjected to various determining survival and death
      signals. Cell death in the core of the infarction and in the adult brain is
      usually considered a passive phenomenon, although events largely depend on the
      partial or complete disruption of crucial metabolic pathways. Cell death in the
      penumbra is currently considered an active process largely dependent on the
      activation of cell death programs leading to apoptosis. Yet cell death in the
      penumbra includes apoptosis, necrosis, intermediate and other forms of cell
      death. A rather simplistic view implies poor prospects regarding cell survival in
      the core of the infarction and therapeutic expectations in the control of cell
      death and cell survival in the penumbra. However, the capacity for
      neuroprotection depends on multiple factors, primarily the use of the appropriate
      agent, at the appropriate time and during the appropriate interval. Understanding
      the mechanisms commanding cell death and survival area is as important as
      delimiting the therapeutic time window and the facility of a drug to effectively
      impact on specific targets. Moreover, the detrimental effects of homeostasis and
      the activation of multiple pathways with opposing signals following ischemic
      stroke indicate that better outcome probably does not depend on a single compound
      but on several drugs acting in combination at the optimal time in a particular
      patient.

PMID- 16651811
TI  - Vascular protection in brain ischemia.
AB  - Vascular damage occurring after cerebral ischemia may lead to a worse outcome in
      patients with ischemic stroke, as it facilitates edema formation and hemorrhagic
      transformation. There are several phases in the development of vascular injury
      (acute, subacute and chronic) and different mediators act in each one.
      Therapeutic options to avoid vascular injury must be focused on acting in each
      phase. However, even though experimental studies have demonstrated the benefit of
      therapeutic interventions both in the acute and chronic phases of cerebral
      ischemia, only the chronic phase offers a therapeutic window sufficiently wide
      enough to provide vascular protection in clinical practice. Several drugs
      including erythropoietin and HMG-CoA reductase inhibitors (statins),
      antihypertensive (angiotensin modulators), antibiotics (minocycline) and
      antihyperglycemic drugs (thiazolidinediones) have been proved to provide vascular
      protection in patients with ischemic stroke. Anti-inflammatory, antioxidant, and
      antiapoptotic actions are responsible for the vascular protective effect related
      to these drugs.

PMID- 16651812
TI  - Gene expression in cerebral ischemia: a new approach for neuroprotection.
AB  - Cerebral ischemia is one of the strongest stimuli for gene induction in the
      brain. Hundreds of genes have been found to be induced by brain ischemia. Many
      genes are involved in neurodestructive functions such as excitotoxicity,
      inflammatory response and neuronal apoptosis. However, cerebral ischemia is also
      a powerful reformatting and reprogramming stimulus for the brain through
      neuroprotective gene expression. Several genes may participate in both cellular
      responses. Thus, isolation of candidate genes for neuroprotection strategies and
      interpretation of expression changes have been proven difficult. Nevertheless,
      many studies are being carried out to improve the knowledge of the gene
      activation and protein expression following ischemic stroke, as well as in the
      development of new therapies that modify biochemical, molecular and genetic
      changes underlying cerebral ischemia. Owing to the complexity of the process
      involving numerous critical genes expressed differentially in time, space and
      concentration, ongoing therapeutic efforts should be based on multiple
      interventions at different levels. By modification of the acute gene expression
      induced by ischemia or the apoptotic gene program, gene therapy is a promising
      treatment but is still in a very experimental phase. Some hurdles will have to be
      overcome before these therapies can be introduced into human clinical stroke
      trials.

PMID- 16651813
TI  - Ischemic preconditioning: a novel target for neuroprotective therapy.
AB  - Ischemic preconditioning involves a brief exposure to ischemia in order to
      develop a tolerance to injurious effects of prolonged ischemia. The molecular
      mechanisms of neuroprotection that lead to ischemic tolerance are not yet
      completely understood. However, it seems that two distinct phases are involved.
      Firstly, a cellular defense function against ischemia may be developed by the
      mechanisms inherent to neurons such as posttranslational modification of proteins
      or expression of new proteins via a signal transduction system to the nucleus.
      Secondly, a stress response and synthesis of stress proteins (heat shock
      proteins) may be activated. These mechanisms are mediated by chaperones. The
      objective of ischemic preconditioning research is to identify the underlying
      endogenous protective cellular receptors and signaling cascades, with the long
      term goal of allowing therapeutic augmentation of the endogenous protective
      mechanisms in cerebral ischemia and possibly development of new neuroprotective
      strategies for ischemic stroke treatment.

PMID- 16651814
TI  - Estrogens as neuroprotectants against ischemic stroke.
AB  - Estrogens have proven vasoprotective properties against atherosclerosis that
      depend on the direct effect on vascular smooth muscle and endothelium and on
      systemic actions that imply serum lipids, coagulation and fibrinolytic cascades,
      vasoactive proteins and antioxidant systems. They also have neuroprotective
      effects against cerebral ischemia that include antioxidant and anti-inflammatory
      effects, modulation of protein synthesis, inhibition of apoptosis and trophic
      effects and preservation of microvascular blood flow in the ischemic area.
      Estrogenic actions depend on activation of specific estrogen receptors that
      modulate gene expression and produce long-term effects on vascular endothelial
      and smooth muscle cells, neurons and glia, on interaction with plasma membrane
      sites that produce rapid non-genomic actions and also on receptor-independent
      mechanisms. This paper reviews what it is known about the mechanisms underlying
      the vaso- and neuroprotective effects of estrogens. Experimental and clinical
      evidences of such protective effects are also discussed. Therapeutical
      implications for stroke prevention and treatment derived from the available
      evidence are considered.

PMID- 16651815
TI  - Neurorepair versus neuroprotection in stroke.
AB  - Stroke is the second to third leading cause of death and the main cause of
      severe, long-term disability in adults. However, treatment is almost reduced to
      fibrinolysis, a therapy useful in a low percentage of patients. Given that the
      immediate treatment for stroke is often unfeasible in the clinical setting, the
      need for new therapy strategies is imperative. After stroke, the remaining
      impairment in functions essential for routine activities, such as movement
      programming and execution, sensorimotor integration, language and other cognitive
      functions have a deep and life-long impact on the quality of life. An interesting
      point is that a slow but consistent recovery can be observed in the clinical
      practice over a period of weeks and months. Whereas the recovery in the first few
      days likely results from edema resolution and/or from reperfusion of the ischemic
      penumbra, a large part of the recovery afterwards is due mainly to brain
      plasticity, by which some regions of the brain assume the functions previously
      performed by the damaged areas. Neurogenesis and angiogenesis are other possible
      mechanisms of recovery after stroke. An understanding of the mechanisms
      underlying functional recovery may shed light on strategies for neurorepair, an
      alternative with a wide therapeutic window when compared with neuroprotective
      strategies.

PMID- 16651816
TI  - The ischemic penumbra: a new opportunity for neuroprotection.
AB  - The development of acute stroke therapies has yielded only limited success and
      many failures in multiple clinical trials. The target of acute stroke therapy is
      that portion of the ischemic region that is still potentially salvageable, i.e.
      the ischemic penumbra. Neuroprotective drugs have the potential to prevent a
      portion of the ischemic penumbra from evolving into infracted tissue and
      designing trials that target neuroprotective drugs at patients with persistent
      penumbra should enhance the likelihood of a positive outcome. Currently,
      diffusion and perfusion MRI has the potential to approximate the location and
      persistence of the ischemic penumbra and can be used in clinical trials to select
      appropriate patients for inclusion and to evaluate a meaningful treatment effect.
      Perfusion CT may also have similar capabilities. Use of these imaging modalities
      in clinical trials and ultimately in clinical practice will likely help in the
      development and utilization of novel neuroprotective drugs.

PMID- 16651817
TI  - Evolving paradigms for neuroprotection: molecular identification of ischemic
      penumbra.
AB  - Ischemic penumbra defines the existence of tissue at risk of infarction and which
      is, hence, potentially salvageable and the target for current stroke reperfusion
      and neuroprotective therapies. Penumbral tissue evolves toward irreversibly
      damaged tissue at different rates in individual stroke patients yielding
      different therapeutic windows depending on the individual duration of risk of
      infarction of this tissue. An accurate identification of the penumbra is then
      necessary in order to individualize the window of opportunity for therapeutic
      interventions. Imaging techniques, although helpful, may not give the most
      accurate information as to the existence of penumbra given that the threshold for
      identification of penumbra varies depending on the technique used. A better
      identification of the true penumbral tissue might be based on the cascade of
      molecular events that are responsible for the evolution of the penumbra toward
      infarcted tissue. Multiple penumbras can be defined in molecular terms taking
      into account which vessel is occluded, the time of evolution of the ischemia, the
      degree of the ischemia, and the sensitivity to ischemia of the different cells.
      Future studies are necessary to clarify whether the enhancement of cytoprotective
      mechanisms, and/or the block of cytotoxic mechanisms confirming the existence of
      penumbra at different times of ischemic evolution, are effective neuroprotective
      strategies.

PMID- 16651818
TI  - Deterioration in acute ischemic stroke as the target for neuroprotection.
AB  - The prevention and treatment of progressing stroke should be one of the main
      therapeutic targets of neuroprotective therapies. Despite the high prevalence of
      progressing stroke in acute stroke (25-35%) and its importance as a predictor of
      poor outcome, no treatment capable of preventing early neurological deterioration
      (END) or of reducing its impact has yet been developed. It is essential that our
      understanding of END's underlying mechanisms be improved as it is currently not
      possible to predict its occurrence accurately. Published studies to date have
      been unable to identify a clinical profile which reliably predicts those patients
      likely to suffer neurological deterioration in the very early acute phase of
      ischemic stroke. In the following pages, we will discuss the present situation
      with regard to neurological worsening in general, paying special attention to END
      given the prognostic and therapeutic implications of this common condition.
      Factors associated with neurological deterioration and the potential mechanisms,
      particularly excitotoxic theory, are discussed.

PMID- 16651819
TI  - Non-pharmacological neuroprotection: role of emergency stroke management.
AB  - Acute stroke should be considered a medical emergency, where actions taken in the
      first hours are fundamental for achieving recovery of the damaged cerebral tissue
      and a better prognosis for the patient. Recanalization and neuroprotective
      treatment has been used with mixed results. The effectiveness observed in the
      first hours with thrombolytic drug treatment is only applicable to a small
      percentage of patients, and attempts to widen this treatment window have not yet
      proved fruitful. Pharmacological neuroprotective treatment has not yet
      demonstrated the clinical effectiveness observed in experimental models. The
      concept of neuroprotection in cerebral ischemia also involves a series of
      mechanisms that take place at the cerebral level following vascular occlusion. In
      this context, it should be borne in mind that a series of physiological functions
      usually involved in the cerebral metabolism (control of blood pressure, of
      temperature, of glycemia and of arterial oxygen saturation) play a key role in
      modulation of the ischemic process. Changes in the control of these mechanisms
      may aggravate the process of cerebral damage in the first hours of ischemic
      stroke. In this work we review the prognostic importance of the main mechanisms
      that may influence the acute phase of cerebral ischemic stroke, as well as their
      therapeutic management and control in the clinical situation.

PMID- 16651820
TI  - Neuroprotection in malignant MCA infarction.
AB  - Massive unilateral hemispheric infarction often develops progressive postischemic
      edema that leads to a malignant course of stroke with mortality of up to 80% with
      conventional medical therapies. Hypothermia and decompressive hemicraniectomy
      have shown neuroprotective effects in several animal models of focal transient
      and permanent MCA occlusion by reducing infarct size and improving neurological
      outcome. Our aim in this paper was to review the possible mechanisms of both
      therapies as well as the optimal time window and duration of application of each
      treatment in animal model and in human malignant MCA infarction reported in the
      literature.

PMID- 16651821
TI  - Neuroprotection in vascular dementia.
AB  - Vascular dementia (VaD) is the second most common form of dementia after
      Alzheimer's disease (AD), and one of the major causes of mental and physical
      disability in developed countries. As such, the identification and implementation
      of strategies which prevent the development of the condition or enable
      improvements in patients with VaD are healthcare objectives of the first order.
      VaD is now regarded as a combined group of clinical-pathological entities rather
      than one disease, that is, multiple pathogenic mechanisms and lesion types
      underlie a cognitive impairment of vascular origin. The clinical diagnosis of VaD
      is complex and difficult because of the heterogeneous nature of its clinical
      presentation and progression and the low sensitivity of existing clinical
      criteria. Moreover, there is growing evidence of the epidemiological significance
      of mixed forms of dementia, and that ischemic processes may precipitate and
      exacerbate cognitive impairment in AD. Numerous compounds have been proposed as
      potentially useful in the treatment of patients with VaD, comprising
      vasodilatative, antithrombotic, hemorrheological, nootropic, antiserotoninergic
      and, most recently, antiglutamatergic and cholinergic approaches. In spite of
      some initially favorable reports based on the use of memantine, donepezil and
      galantamine, there is as yet no conclusive evidence of a definitive treatment for
      VaD. Unsatisfactory results from VaD drug trials may be attributed in part to the
      diversity of the patients included (underlying pathogenic mechanisms, number,
      type, and location of vascular lesions), and to methodological limitations in the
      design of the trials (outcome measures, end-points, size, follow-up period). The
      treatment of modifiable vascular risk factors - hypertension, diabetes mellitus,
      hypercholesterolemia and heart disease - is an important strategy for the
      reduction of the risk of dementia, and is likely to slow the progress of
      cognitive decline.

PMID- 16651822
TI  - Thrombolysis and neuroprotection in cerebral ischemia.
AB  - Stroke is a major cause of death and disability worldwide. The resulting burden
      on society grows with the increase in the incidence of stroke. The term brain
      attack was introduced to describe the acute presentation of stroke and emphasize
      the need for urgent action to remedy the situation. Though a large number of
      therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium
      channel blockers and antioxidants, have been used or are being evaluated, there
      is still a large gap between the benefits of these agents and the properties of
      an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour
      time window has been shown to improve the outcome of patients with ischemic
      stroke. Understanding the mechanisms of injury and neuroprotection in these
      diseases is important to target news sites for treating ischemia. Better
      evaluation of the drugs and increased similarity between the results of animal
      experimentation and in the clinical setting requires critical assessment of the
      selection of animal models and the parameters to be evaluated. Our laboratory has
      employed a rat embolic stroke model to investigate the combination of rtPA with
      citicoline as compared to monotherapy alone and investigated whether
      neuroprotection should be provided before or after thrombolysis in order to
      achieve a greater reduction of ischemic brain damage.

PMID- 16651823
TI  - Other neuroprotective therapies on trial in acute stroke.
AB  - New neuroprotective agents on trial may potentially offer benefit to stroke
      patients without the associated hemorrhagic risk of thrombolytic therapy.
      Clinical investigation of these drugs has been designed to obtain the highest
      probability of success, or concentrates on the salvageable ischemic brain and use
      infarct growth on MRI as a surrogate end-point. Nine substances in 10 trials are
      currently being tested in three therapeutical strategies in patients with acute
      ischemic stroke. These strategies focus on: (1) the optimal management of serum
      glucose with the infusion of glucose, insulin and potassium to induce and
      maintain euglycemia; (2) the modulation of the inflammatory response with
      recombinant human interferon-beta(1a), and (3) interfering with the ischemic
      cascade using magnesium, albumin, the metal iron chelator DP-b99, the AMPA
      receptor antagonist zonampanel, the serotonin agonists repinotan and piclozotan,
      the free radical scavenger cerovive, and the membrane modulator citicoline.
      Future directions should develop neuroprotective compounds that are safe and well
      tolerated, are effective in a broad range of patients and can be used with or
      without rt-PA.

PMID- 16651824
TI  - Characterization of osteogenically induced adipose tissue-derived precursor cells
      in 2-dimensional and 3-dimensional environments.
AB  - Earlier reports on a putative precursor cell population in adipose tissue showed
      differentiation along several mesodermal lineages, leading some to think that
      adipose tissue can be a source of cells applicable in regenerative medicine.
      However, characterizations of these adipose-derived precursor cells (ADPC) in the
      3-dimensional (3-D) environment, especially within the area of bone-specific
      composite scaffolds, have been lacking. In this study, ADPC plated on culture
      flasks or seeded on medical grade polycaprolactone-tricalcium phosphate scaffolds
      (mPCL-CaP) were able to differentiate along the osteogenic lineages in both 2-D
      and 3-D environments as assessed with immunohistochemistry of osteo-related
      proteins, reverse transcriptase-polymerase chain reactions and alkaline
      phosphatase assay. The mPCL-CaP scaffolds provided adipose-derived cells (ADC)
      with a suitable environment as determined by DNA and metabolic assays, light,
      confocal and scanning electron microscopy. Flow cytometry revealed ADC to be
      CD29+, CD44+, CD73+, CD90+ and CD14-, CD31-, CD34-, CD45-, CD71-, and therefore
      showed the absence of hematopoietic stem cells but possibly the presence of
      pericytes and mescenchymal stem cells with osteogenic potential. The results of
      this study demonstrated the potential of using ADPC in combination with mPCL-CaP
      scaffolds for bone regenerative medicine.

PMID- 16651825
TI  - The neural tube is required to maintain primary segmentation in the sclerotome.
AB  - Primary segmentation in vertebrates is considered to be an intrinsic property of
      the presomitic paraxial mesoderm controlled by a number of interconnected
      oscillating signals. Re-segmentation, in contrast, has been shown to depend on
      signals from the axial structures. Here we report the requirement of the neural
      tube for maintenance but not formation of primary segmentation in chick embryos.
      Unilateral removal of the neural tube, next to the anterior presomitic mesoderm,
      caused disturbed development of the neural arches and the spinous processes. But
      already 24 h postsurgery, the sclerotome showed loss of primary segmentation in
      the craniocaudal axis. Cells strongly expressing twist and not showing any
      segmentation were located dorsomedially between the remaining left half of the
      neural tube and the right side dermomyotome, which frequently was truncated
      medially.

PMID- 16651826
TI  - Immunohistochemical detection of macrophage migration inhibitory factor in fetal
      and adult bovine epididymis: release by the apocrine secretion mode?
AB  - Originally defined as a lymphokine inhibiting the random migration of
      macrophages, the macrophage migration inhibitory factor (MIF) is an important
      mediator of the host response to infection. Beyond its function as a classical
      cytokine, MIF is currently portrayed as a multifunctional protein with growth
      regulating properties present in organ systems beyond immune cells. In previous
      studies, we detected substantial amounts of MIF in the rat epididymis and
      epididymal spermatozoa, where it appears to play a role during post-testicular
      sperm maturation and the acquisition of fertilization ability. To explore its
      presence in other species not yet examined in this respect, we extended the range
      of studies to the bull. Using a polyclonal antibody raised against MIF purified
      from bovine eye lenses, we detected MIF in the epithelium of the adult bovine
      epididymis with the basal cells representing a prominently stained cell type. A
      distinct accumulation of MIF at the apical cell pole of the epithelial cells and
      in membranous vesicles localized in the lumen of the epididymal duct was obvious.
      In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas
      MIF accumulation was evident at the apical cell surface and in apical
      protrusions. By immunoelectron microscopy of the adult bovine epididymis, we
      localized MIF in apical protrusions of the epithelial cells and in luminal
      membrane-bound vesicles that were found in close proximity to sperm cells.
      Although the precise origin of the MIF-containing vesicles remains to be
      delineated, our morphological observations support the hypothesis that they
      become detached from the apical surface of the epididymal epithelial cells.
      Additionally, an association of MIF with the outer dense fibers of luminal
      spermatozoa was demonstrated. Data obtained in this study suggest MIF release by
      an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized
      in the basal cells of the epithelium and in the connective tissue could be
      responsible for regulating the migration of macrophages in order to avoid contact
      of immune cells with spermatozoa that carry a wide range of potent antigens.

PMID- 16651827
TI  - Anatomical study and proportional analysis of the pig spleen arterial segments.
AB  - A systematic study was performed in 31 pig spleens to provide an analysis of the
      splenic arterial segmentation and an analysis of the proportional area of each
      segment. There were two independent arterial segments in all cases, a dorsal and
      a ventral. The dorsal segment was smaller than the ventral segment, presenting
      16.81 and 83.19% as the median percentage of the total area of the spleen,
      respectively. In conclusion, the pig arterial segments are quite similar to those
      of dog, buffalo, goat, and sheep, where there is a small dorsal segment and a
      large ventral segment, and somewhat similar to the human spleen, where there are
      two segments as well, though with a similar area.

PMID- 16651828
TI  - Ultrastructural localization of tritiated histidine in down feathers of the
      chick.
AB  - During the differentiation of cells in developing down feathers of the chick
      embryo, keratin and associated proteins are synthesized. Previous studies
      indicated that a histidine-rich protein with a different amino acid composition
      but similar molecular weight and localization of feather keratin is produced in
      forming feathers. The precise localization of the histidine-rich protein, either
      in feather barb and barbule cells and/or in supportive cells (sheath, barb vane
      ridge and cylindrical cells) is not known. The present ultrastructural
      autoradiographic study on developing feathers in the chick embryo shows the
      subcellular localization of histidine-labeled molecules, presumably representing
      histidine-rich proteins. Two hours after injection of tritiated histidine in
      chick embryos, the labeling is mainly present in the cytoplasm or is associated
      with forming keratin filaments of barb and barbule cells. Neither keratin
      filaments nor dense granules of barbule cells are specifically or prevalently
      labeled with tritiated histidine. No labeling is seen in periderm granules or in
      keratinaceous dark granules of sheath and barb vane ridge cells localized among
      barbule cells. The present study indicates that histidine-rich material rapidly
      associates with newly synthesized filaments of keratin. This observation suggests
      that histidine-labeled material contributes to the formation of long keratin
      filaments with axial orientation that are utilized for the elongation of barb and
      barbule cells.

PMID- 16651829
TI  - Immunocytochemical characterization of Delta-opioid and Mu-opioid receptor
      protein in the bovine pineal gland.
AB  - Opioidergic innervation has been identified in the mammalian pineal gland.
      Recently, opioid receptors in bovine pineal glands have been characterized; the
      activation of these receptors leads to the stimulation of melatonin synthesis. In
      this study, the precise localization of opioid receptors in bovine pineal glands
      was determined by an immunohistochemical technique using antibodies raised
      against delta-opioid and mu-opioid receptors. Immunoreactivity of these two
      receptors was present at a moderate level in pinealocytes. A double-labeling
      study has shown that delta-opioid receptors are localized predominantly with mu
      opioid receptors in the same pinealocytes. These immunopositive pinealocytes are
      often located in a group; however, some of them are dispersed individually. In
      addition, both types of receptors were found in glial cells and processes. A
      small number of delta-receptor-immunoreactive nerve fibers were observed in the
      perivascular space and intraparenchyma of the pineal gland. Mu-opioid receptor
      immunoreactivity was found in a number of nerve fibers throughout the gland, and
      in terminal-like dots on pinealocytes. There was immunocolocalization between
      delta-opioid receptors or mu-opioid receptors and leu-enkephalin in some nerve
      fibers. The results of this study indicate that the modulatory effect of the
      opioid system on melatonin secretion in pineal glands might act via opioid
      receptors on pinealocytes, whereas receptors located on nerve fibers might
      modulate the release of opioid peptides.

PMID- 16651830
TI  - A bioequivalence study of two oral desmopressin tablet formulations.
AB  - The present study was carried out to test bioequivalence between two different
      oral desmopressin formulations. Sixty healthy volunteers were enrolled in the
      study and were randomly assigned to receive the test (T) and reference (R) drug
      in a two-period two-sequence, crossover, analyst-blinded study design. Subjects
      received an oral dose of 400 mug of desmopressin acetate separated by a wash-out
      period of at least 7 days. The area under the concentration-time curve (AUC) over
      12 h in plasma and the maximum concentration (C(max)) were compared by analysis
      of variance (ANOVA) after log transformation. The mean ratios of the T to R drug
      were within the bioequivalence boundaries with mean values of 1.00 (90% CI: 0.87
      1.14) and 1.03 (90% CI: 0.92-1.15) for AUC(0-t) and AUC(0-inf), respectively. For
      the C(max), the mean ratio of the T to R drug was 0.97 (90% CI: 0.87-1.08). The
      rate and the extent of oral desmopressin absorption were identical for both
      formulations. Hence, the desmopressin test tablet met all bioequivalence criteria
      of the marketed reference desmopressin tablet.

PMID- 16651831
TI  - Trends in prosthodontics.
AB  - Prosthodontics is concerned with the impact of tooth or tissue damage and partial
      or complete loss of teeth on oral function in its broadest sense. It deals with
      this largely through prosthetic replacement. The discipline occupies a major
      portion of a dental school curriculum, and dental practitioners usually devote
      much of their practice to prosthodontic services. With the rapid improvement in
      oral health and the reduction of edentulism in many countries, increasing numbers
      of people are retaining more teeth later in life.Gradually,the main focus in
      prosthodontics has shifted from removable dentures to fixed prostheses, while
      implant-supported restorations have attracted intense interest in the dental
      community. Another factor increasingly influencing prosthodontic practice is
      patients' awareness of newer technologies in aesthetic dentistry. Because
      prosthodontic interventions as well as maintenance and repair are by nature
      costly, the global development in the field manifests fundamental inequalities in
      the levels of service that patients can access. Diminishing resources for health
      care in general challenges educators and practitioners of prosthodontics alike.
      This review is an attempt to describe the recent developments in prosthodontics
      and its therapeutic areas, and the impact such developments may have on the
      theory and practice of the discipline.

PMID- 16651832
TI  - The Kuwait cataract outcome study: a 12-month evaluation.
AB  - OBJECTIVE: To assess the frequency of intraopertive difficulties, postoperative
      complications and the visual outcome in cataract surgery performed at the Al
      Bahar Eye Center, Kuwait. SUBJECTS AND METHODS: This case series study is
      comprised of 350 eyes from 325 subjects (169 male, 156 female; 30-78 years, mean
      age 64 years) undergoing consecutive cataract surgery performed at the Al-Bahar
      Eye Center, Kuwait from July 2001 to June 2002. All the eyes underwent extensive
      ophthalmic examinations before and after surgery. Details of surgical procedures,
      including the type of the cataract surgery, intraoperative difficulties or
      complications, postoperative complications, and the visual outcome were
      documented. RESULTS: The extracapsular cataract extraction (ECCE) technique was
      used for 50.2% of the eyes and for the remaining 49.8%, the small-incision
      phacoemulsification technique was used. Of the 350 eyes operated upon, 9.7% had
      coexisting ocular disease which may have affected the best spectacle corrected
      visual acuity (BSCVA). Complications included posterior capsule tears and
      vitreous loss (10%), cystoid macular edema (0.6%) and endophthalmitis (0.9%) of
      the eyes. A BSCVA of 6/12 or better was achieved in 78.3% of the cases.
      CONCLUSION: A high success rate in terms of visual acuity outcome was achieved in
      the cataract surgery. The operative and postoperative complications were similar
      for both techniques, ECCE and phacoemulsification.

PMID- 16651833
TI  - Physicians' perceptions and expectations of pharmacists' professional duties in
      government hospitals in Kuwait.
AB  - OBJECTIVE: The objectives of this study were to evaluate the perceptions,
      expectations and experience of physicians with hospital-based pharmacists in
      Kuwait. MATERIALS AND METHODS: A piloted self-administered questionnaire was hand
      delivered to 200 physicians practicing in four government hospitals in Kuwait.
      Main sections of the questionnaire comprised a series of statements pertaining to
      physicians' perceptions, expectations and experiences with pharmacists. RESULTS:
      One hundred and twenty (60%) questionnaires were returned. At least 57% of
      physicians in Kuwait appear comfortable with pharmacists carrying out patient
      directed roles. In addition, they appeared to have high expectations of
      pharmacists, with 79% of them regarding pharmacists as knowledgeable drug therapy
      experts. Less than 60% considered pharmacists as applying their drug knowledge in
      practice and only 29% agreed that pharmacists routinely counselled their
      patients. There was no correlation between physician variables such as number of
      years since graduation from medical school, age, area of practice and their
      perceptions of pharmacists. CONCLUSION: Physicians in Kuwait appear comfortable
      with pharmacists providing a broad range of services but appear somewhat less
      comfortable with pharmacists' provision of direct patient care. Physicians
      considered pharmacists knowledgeable drug therapy experts, but regarded them as
      not routinely providing a broad range of higher-level pharmacy services.

PMID- 16651834
TI  - The prevalence of neuropathy and relationship with risk factors in diabetic
      patients: a single-center experience.
AB  - OBJECTIVE: To determine the rate of distal symmetrical polyneuropathy (DSP) in
      patients with type 2 diabetes mellitus, to evaluate the role of history,
      neurological examination and the electrodiagnostic methods in the diagnosis of
      DSP, and to determine the association between electromyography-supported
      neuropathy (ESN), neuropathic complaints (NCs) and risk factors. SUBJECTS AND
      METHODS: A total of 191 type 2 DM patients (109 female, 82 male; mean age 58.7 +/
      10 years) were recruited. The NCs were recorded. All patients had
      electromyographic (EMG) examinations. The relationship between ESN, NCs and risk
      factors were evaluated. RESULTS: Of the 191 patients, 83 (43.5%) had DSP on EMG
      examinations and 92 (48.2%) patients suffered from NCs. Among the ESN patients, a
      significant relationship existed with HbA1(c) level, illness duration, smoking,
      male gender or insulin usage (p < 0.05) but not with age, hypertension,
      hypercholesterolemia or hypertriglyceridemia. The frequency of NCs was higher in
      patients with ESN. There was also a significant association between NCs and ESN
      (p < 0.05). The presence of NCs was not related to age, gender, smoking,
      hypertension, hypercholesterolemia and hypertriglyceridemia (p > 0.05) but NCs
      were correlated to HbA1(c) level, illness duration and insulin usage (p < 0.05).
      CONCLUSION: Our data show that a strong association exists between the presence
      of DSP and illness duration, HbA1(c), smoking, thereby indicating that cessation
      of smoking and near normal glycemic control would be additional precautions to
      delay the beginning or progression of polyneuropathy.

PMID- 16651835
TI  - Smoking prevalence and its effect on dental health attitudes and behavior among
      dental students.
AB  - OBJECTIVE: To determine smoking prevalence and its effect on dental health
      attitudes and behavior among dental students in Jordan. SUBJECTS AND METHODS: A
      cross-sectional study of 314 dental students was conducted at Jordan University
      of Science and Technology. Subjects were surveyed using a modified version of the
      Hiroshima University Dental Behavior Inventory (HU-DBI) questionnaire.
      Multivariate logistic regression analyses were performed to study differences
      between male smokers and nonsmokers only. RESULTS: The response rate was 83.7%,
      with 48% males and 52% females. The prevalence of smoking was 17.2%. Smoking was
      more prevalent among male students (31%) than female (4.3%). For male students,
      the multivariate logistic regression analysis showed 6 items that were different
      between smokers and nonsmokers. Nonsmokers tended to brush their teeth more often
      than smokers (OR 8.67, 95% CI 1.66-45.25); claimed that they had never been
      professionally taught how to brush their teeth (OR 11.15, 95% CI 1.89-65.67);
      believed that they spend too much time brushing their teeth (OR 12.24, 95% CI 2.0
      75.05); were more concerned about having bad breath (OR 41.86, 95% CI 3.44-58.75)
      and were more concerned about the color of their gums (OR 8.04, 95% CI 1.55
      41.84). CONCLUSIONS: Smoking prevalence among male dental students in Jordan was
      high, 7 times greater than for females. Male smokers and nonsmokers had different
      attitudes and oral health behaviors as indicated by the study survey.

PMID- 16651836
TI  - Seasonal and temporal variations in the population and biting habit of mosquitoes
      on the Atlantic coast of Lagos, Nigeria.
AB  - OBJECTIVES: To determine the hourly density of vector mosquitoes in coastal
      Nigeria, compare seasonal human-biting and sporozoite rates in the vector
      density, locate breeding sites of mosquitoes, and determine larval population at
      breeding sites. MATERIALS AND METHODS: Indoor and outdoor mosquitoes of a coastal
      Nigerian community were caught during early and late wet seasons and in the
      harmattan period, a time of dusty wind from the Sahara on the western coast of
      Africa. Larvae were collected from various locations during the study period. The
      mosquitoes were physically characterized and their salivary glands dissected for
      sporozoite rate. Larvae density was calculated. Human-biting rate was calculated
      for Anopheles gambiae complex. RESULTS: Of the 4,317 female A. gambiae complex
      collected during the night bait catches, 3,543 (82.1%) were from outdoors and 774
      (17.9%) from indoors during the three seasons. The maximum human-biting rate
      approached 25/h and the sporozoite rate was almost 3.0%. These vector mosquitoes
      were mainly outdoor biting and midnight feeding. Of the 1,269 Anopheles
      mosquitoes collected with pyrethrum spray catches, 1,245 (98.1%) were A. gambiae
      complex. There was no significant difference in the entomological inoculation or
      sporozoite rates during the three seasons of study. There was a preponderance of
      A. gambiae complex larvae from larval collection. CONCLUSION: Findings from this
      study should be useful in the implementation of Integrated Vector Management for
      the control of malaria in coastal and noncoastal areas of Nigeria.

PMID- 16651837
TI  - Impact of operator on determining functional parameters of nuclear medicine
      procedures.
AB  - OBJECTIVE: The study was designed to assess the significance of the interoperator
      variability in the estimation of functional parameters for four nuclear medicine
      procedures. MATERIALS AND METHODS: Three nuclear medicine technologists with
      varying years of experience processed the following randomly selected 20 cases
      with diverse functions of each study type: renography, renal cortical scans,
      myocardial perfusion gated single-photon emission computed tomography (MP-GSPECT)
      and gated blood pool ventriculography (GBPV). The technologists used the same
      standard processing routines and were blinded to the results of each other. The
      means of the values and the means of differences calculated case by case were
      statistically analyzed by one-way ANOVA. The values were further analyzed using
      Pearson correlation. RESULTS: The range of the mean values and standard deviation
      of relative renal function obtained by the three technologists were 50.65 +/- 3.9
      to 50.92 +/- 4.4% for renography, 51.43 +/- 8.4 to 51.55 +/- 8.8% for renal
      cortical scans, 57.40 +/- 14.3 to 58.30 +/- 14.9% for left ventricular ejection
      fraction from MP-GSPECT and 54.80 +/- 12.8 to 55.10 +/- 13.1% for GBPV. The
      difference was not statistically significant, p > 0.9. The values showed a high
      correlation of more than 0.95. Calculated case by case, the mean of differences
      +/- SD was found to range from 0.42 +/- 0.36% in renal cortical scans to 1.35 +/-
      0.87% in MP-GSPECT with a maximum difference of 4.00%. The difference was not
      statistically significant, p > 0.19. CONCLUSION: The estimated functional
      parameters were reproducible and operator independent as long as the standard
      processing instructions were followed.

PMID- 16651838
TI  - Persistence, recurrence, and progression rates of superficial bladder tumours
      after resection using the differentiated technique.
AB  - OBJECTIVE: To investigate whether the differentiated resection technique for
      excising superficial bladder cancer leads to higher recurrence and progression
      rates as compared with regular resection. SUBJECTS AND METHODS: We evaluated 163
      patients, 66 undergoing a differentiated and 97 a regular resection. All patients
      underwent a routine second resection within 6-10 weeks. Recurrence and
      progression rates as well as tumour persistence on second resection were
      analyzed. RESULTS: Patients with differentiated resections of bladder tumours did
      not have higher tumour recurrence and progression rates. Also, these patients had
      a significantly higher percentage of tumour-free second resections (p = 0.03).
      CONCLUSION: The differentiated resection technique for excising superficial
      bladder cancer has no negative influence on recurrence and progression rates, but
      it leads to a reduced tumour persistence.

PMID- 16651839
TI  - Comparison of free radical scavenging activity of Siamese neem tree (Azadirachta
      indica A. Juss var. siamensis Valeton) leaf extracts prepared by different
      methods of extraction.
AB  - OBJECTIVE: The aim of this study was to investigate the antioxidant activity of
      the aqueous extracts of leaves of Siamese neem tree (Azadirachta indica A. Juss
      var. siamensis Valeton) from several extracting and drying methods using 2,2
      diphenyl-1-picrylhydrazyl (DPPH)-scavenging assay. MATERIALS AND METHODS: The
      leaves of Siamese neem tree were extracted using percolation, decoction,
      maceration, soxhlet extraction, freeze drying or spray drying methods. The
      extract was tested for antioxidant activity using DPPH-scavenging assay. Thin
      layer chromatography of the extract from decoction was also investigated.
      RESULTS: The freeze drying method gave the highest yield (51.50%, w/w) of crude
      extract, while decoction gave the most effective DPPH-scavenging activity
      (EC(50): 31.4 microg/ml). Thin-layer chromatography analysis was used to screen
      the leaf extract obtained using decoction, and the chromatogram showed spots
      corresponding to quercetin and rutin flavonoids which exhibited antioxidant
      activities (EC(50): 2.29 and 34.67 microg/ml, respectively). CONCLUSION: Siamese
      neem tree leaf extracts possessed free radical scavenging activity against the
      DPPH radical. The most active extract was obtained with the leaf decoction
      method. It showed antioxidant activity with EC(50) of 31.4 microg/ml.

PMID- 16651840
TI  - Comparative evaluation of BacT/ALERT 3D and BACTEC systems for the recovery of
      pathogens causing bloodstream infections.
AB  - OBJECTIVE: To compare BacT/ALERT (BTA) and BACTEC 9240 (BAC), two continuously
      monitoring automated blood culture systems, for the recovery of bloodstream
      pathogens and standard media available for these systems. MATERIALS AND METHODS:
      Blood samples from 100 adults and 50 paediatric patients suspected of having
      bloodstream infections were inoculated at the bedside into non-vented BTA and BAC
      standard blood culture bottles and incubated in their respective instruments. The
      time to growth detection (TD) was recorded for each bottle that became positive.
      A quantitative assay was also carried out with 5 standard bloodstream pathogens
      to assess TD of each pathogen as well as the quantity of organisms recovered.
      RESULTS: A total of 23 isolates representing true infections were recovered by
      both BTA and BAC bottles, indicating a blood culture positivity rate of 15.3%, 18
      (78.3%) by BTA bottles and 13 (56.5%) by BAC. Proteus mirabilis, Pseudomonas
      aeruginosa and Clostridium perfringens were recovered only by the BTA system. The
      average TDs were 19.0 and 24.6 h for BTA and BAC, respectively. Analysis of the
      quantitative growth of known pathogens in both systems was more or less the same
      for Staphylococcus aureus, Escherichia coli and P. aeruginosa but slightly
      different for Haemophilus influenzae and Streptococcus pneumoniae. The anaerobic
      bottle ofthe BTA did not support the growth of H. influenzae below an inoculum of
      10(10) CFU/ml whereas the BAC did so at a lower inoculum of 10(8) CFU/ml. TD for
      S. pneumoniae in the BTA was about half of that in the BAC. CONCLUSIONS: The BTA
      system appears to be more efficient in detecting common bloodstream pathogens asa
      higher inoculum is needed for the BAC system to detect the same organism.

PMID- 16651841
TI  - Comorbidity of constrictive pericarditis and hemophilia A.
AB  - OBJECTIVE: To report a case of comorbidity of constrictive pericarditis and
      hemophilia A. CLINICAL PRESENTATION AND INTERVENTION: A 21-year-old male with
      hemophilia A was referred to our clinic and was examined with the subsequent
      evaluation of shortness of breath, leg edema and ascites. Clinical and laboratory
      examinations were performed. The results were consistent with constrictive
      pericarditis (CP), and the symptoms were completely relieved following
      institution of medical therapy. CONCLUSION: Because hemophilia A and pericarditis
      may be coincidentally present clinical conditions, avoidance of surgical
      procedures in hemophilic patients is preferable unless the resolution of the
      symptoms of pericarditis cannot be effected by medical therapy.

PMID- 16651842
TI  - Varicella-associated purpura fulminans: chicken pox is not always benign.
AB  - OBJECTIVE: To report a 6-year-old boy with post-chicken pox purpura fulminans
      (PF). CLINICAL PRESENTATION AND INTERVENTION: A 6-year-old boy presented with
      purpura of the legs that rapidly progressed to other parts of the limbs and the
      buttocks. The patient had had chicken pox 10 days prior to presentation. He was
      afebrile and the chicken pox lesions were dry. He received anti-coagulants, a
      large volume of fresh frozen plasma, immunoglobulin and steroids. The skin
      lesions regressed but both hands and parts of the lower limbs remained necrotic;
      the patient was transferred to an orthopaedic hospital for amputation and skin
      grafting. CONCLUSION: This case report shows that PF can occur as a post
      infection syndrome after primary varicella. Early and aggressive treatment of
      post-chicken pox PF might reduce the mortality and morbidity associated with this
      condition.

PMID- 16651843
TI  - Disseminated Penicillium marneffei infection with fungemia and endobronchial
      disease in an AIDS patient in China.
AB  - OBJECTIVE: To present a rare Chinese case of disseminated Penicillium marneffei
      infection with fungemia and endobronchial disease in an AIDS patient. CLINICAL
      PRESENTATION AND INTERVENTION: A 26-year-old policeman who had resided in Guangxi
      Province, China, for 3 years presented to his county hospital with a 2-month
      history of high fever and cough. A provisional diagnosis of pulmonary
      tuberculosis (TB) was made. Accordingly, the patient was treated with anti-TB
      drugs for 1 month but with no clinical improvement; he was then referred to West
      China Hospital. Blood and bone marrow cultures as well as a bronchoscopic biopsy
      were positive for P. marneffei. A confirmatory serologic test for HIV was
      positive. A combination therapy with amphotericin B and itraconazole was
      instituted, and the patient responded well to treatment. CONCLUSION: This case
      shows endobronchial involvement caused by an emerging fungal microorganism. HIV
      positive patients with a history of residence in or travel to southern China and
      a clinical presentation suggestive of TB but responding poorly to anti-TB
      treatment may have P. marneffei infection.

PMID- 16651844
TI  - Moyamoya syndrome with primary antiphospholipid syndrome.
AB  - OBJECTIVES: To report a rare case of moyamoya syndrome with primary
      antiphospholipid syndrome (APS). CLINICAL PRESENTATION AND INTERVENTION: A 41
      year-old woman was admitted with sudden onset of left-sided hemiparesis. Magnetic
      resonance imaging and magnetic resonance angiography of the brain showed
      characteristic features of moyamoya vessels. Laboratory investigations revealed
      raised levels of anticardiolipin antibody. She made a complete and uneventful
      recovery with aspirin and intensive physiotherapy over a period of 2 weeks.
      CONCLUSION: The association of APS and moyamoya disease may present a dilemma in
      management. While APS is often considered to be an indication for giving
      anticoagulation, a trial of antiplatelet agents is preferable to anticoagulation
      because of the risk of bleeding from the fragile moyamoya vessels.

PMID- 16651845
TI  - Unilateral diaphragm paralysis possibly due to cervical spine involvement in
      multiple myeloma.
AB  - OBJECTIVE: To describe a patient with unilateral diaphragmatic paralysis due to
      multiple myeloma (MM) involving the cervical spine and related structures. CASE
      PRESENTATION AND INTERVENTION: A 52-year-old female presented with dyspnea, low
      back and widespread bone pain. She was diagnosed as having MM with vertebral
      involvement and unilateral paralysis of the diaphragm. She received two cycles of
      a chemotherapeutic regimen consisting of vincristine-Adriamycin-dexamethasone.
      The bisphosphonate zoledronic acid was also initiated at the same time. During
      follow-up, the back pain disappeared and the complaint of dyspnea decreased,
      although the paralysis persisted. CONCLUSION: As part of the differential
      diagnosis of bone and back pain, we draw attention to MMand the rare complication
      of diaphragmatic paralysis due to phrenic nerve involvement.

PMID- 16651846
TI  - Sympathectomy causes aggravated lesions and dedifferentiation in large rabbit
      atherosclerotic arteries without involving nitric oxide.
AB  - Previously [Histochem J 1997;29:279-286], we found that sympathectomy induced
      neointima formation in ear but not cerebral arteries of genetically
      hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in
      atherosclerosis, and whether their influence involves vascular NO activity, we
      studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and
      hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6
      hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries
      were studied histochemically, to evaluate differentiation (anti-desmin, anti
      vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in
      vitro myography. In BAs, staining of NI and NS groups was similar. In
      hypercholesterolemic groups, a small neointima developed, more frequently in HS
      segments where smooth muscle cells (SMCs) positive for all antibodies appeared to
      be migrating into the neointima. In FAs, SMCs stained for the three antibodies in
      the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive
      cells in some external medial layers of the NS, HI and HS groups, identical to
      adventitial fibroblasts. Large neointimas of the HS group contained vimentin
      positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or
      FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy
      increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus,
      sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate,
      increasing atherosclerotic lesions, without decreasing NO activity, but has only
      minor effects on BAs.

PMID- 16651847
TI  - Benefits of screening in von Hippel-Lindau disease--comparison of morbidity
      associated with initial tumours in affected parents and children.
AB  - Von Hippel-Lindau (VHL) is a rare autosomal dominant syndrome characterised by
      the association of retinal and CNS haemangioblastomas, phaeochromocytoma and
      renal cell carcinoma. If a child of an affected parent has inherited a VHL
      mutation or the parent's mutation cannot be identified, then clinical screening
      is recommended. We report the clinical features in three parent-offspring pairs
      where the parents have presented clinically with renal cell carcinoma,
      phaeochromocytoma, cerebellar haemangioblastoma and retinal haemangioma, and the
      children have undergone pre-symptomatic screening. During the first screening a
      13-year-old boy was diagnosed with bilateral phaeochromocytoma and later
      developed an endolymphatic sac tumour at 19 years. A right phaeochromocytoma was
      found in a 12-year-old girl who was screened from the age of 4 years and in a 13
      year-old boy screened from 5 years of age. All children were asymptomatic at the
      time of diagnosis. These families demonstrate that clinical screening of children
      at risk of VHL can detect tumours before the first symptoms arise with a
      consequent reduction in morbidity. These observations strongly support the
      recommendation to undertake screening of the children of VHL patients.

PMID- 16651848
TI  - Renal function in patients with abdominal aortic aneurysm. Comparison with
      hypertensive patients.
AB  - AIMS: Renal dysfunction occurs occasionally after the repair of abdominal aortic
      aneurysm (AAA), and preoperative renal function is considered as one of the
      potential causes. The present study was designed to evaluate and compare renal
      function and risk factors of AAA patients with those of hypertensive patients.
      METHODS: We prospectively examined 95 patients with AAA and 72 patients with
      essential hypertension (HT) without other cardiovascular diseases (CVD). Renal
      function, urinary albumin excretion (UAE) and renal scintigraphy were compared.
      Kidney size was calculated using ultrasonography. RESULTS: Serum creatinine and
      creatinine clearance in AAA patients was worse than in HT patients. Smoking
      status was more apparent in AAA patients. Renal artery stenosis occurred in 8
      patients with AAA. Renal scintigraphy showed normal function in 19%, hypofunction
      in 69% and severe dysfunction in 12% of the AAA patients, and normal function in
      42% and hypofunction in 58% of the HT patients (p < 0.0001). Multivariate linear
      regression analysis showed that renal function was related to age, UAE, CVD,
      smoking status and kidney size for all patients, UAE, CVD, smoking status and
      kidney size for AAA patients, and age and kidney size for HT patients.
      CONCLUSION: Renal function of AAA patients was worse than HT patients without
      other CVD. The risk factors for renal dysfunction were different between AAA and
      HT patients. These preoperative conditions may relate to the postoperative renal
      dysfunction seen in AAA patients.

PMID- 16651849
TI  - Effects of anesthesia on plasma and kidney ANG II levels in normotensive and ANG
      II-dependent hypertensive rats.
AB  - BACKGROUND: Previous studies have implicated that normotensive rats with normal
      renal renin activity respond to anesthesia and surgery with greater increases in
      plasma and kidney angiotensin II (ANG II) concentrations than ANG II-dependent
      hypertensive rats with intrarenal renin depletion. In the present study, we
      therefore compared plasma and kidney ANG II levels in anesthetized and conscious
      normotensive and ANG II-dependent hypertensive rats. METHODS: Salt-replete
      Hannover-Sprague-Dawley rats (HanSD) served as controls. As models of ANG II
      dependent hypertension we used: 1st, transgenic rats harboring the Ren-2 renin
      gene (TGR); 2nd, two-kidney, one-clip (2K1C) Goldblatt hypertensive rats, and,
      3rd, ANG II-infused hypertensive rats. As additional model with enhanced renin
      angiotensin system (RAS) activity, salt-depleted HanSD and TGR were employed.
      RESULTS: In anesthetized salt-repleted HanSD, plasma and kidney ANG II levels
      were higher than in salt-repleted TGR, ANG II-infused and 2K1C rats. Salt
      depletion caused marked increases in ANG II levels in HanSD but did not alter
      them in TGR. In contrast, in conscious animals immediately after decapitation
      plasma and kidney ANG II levels were similar in salt-repleted and salt-depleted
      TGR, in ANG II-infused rats, in the clipped kidney of 2K1C rats and in salt
      depleted HanSD and in all these groups they were significantly higher than in
      salt-repleted HanSD. CONCLUSIONS: These findings indicate that anesthesia
      increases plasma and kidney ANG II levels in HanSD to a greater degree than in
      ANG II-dependent models of hypertension. Therefore, the results from studies
      employing anesthetized animals must be interpreted with caution.

PMID- 16651850
TI  - Genomewide oligonucleotide microarray analysis on placentae of pre-eclamptic
      pregnancies.
AB  - OBJECTIVE: Human placentae from normal and pre-eclamptic pregnancies were
      evaluated for possible changes in gene expression by microarray analysis to
      uncover new clues for the research of the etiology of pre-eclampsia. METHODS:
      Placentae from five normal pregnancies and five pregnancies complicated by pre
      eclampsia were collected. mRNA levels of five pre-eclamptic placentae were
      examined using genome-wide 70-mer oligonucleotide microarrays (CapitalBio,
      Beijing, China) in comparison with the pooled control consisting of total RNA
      from five normotensive placentae. RESULTS: Ninety-six genes were found
      consistently down- or up-regulated in at least four pre-eclamptic samples. Most
      of them were related to an imbalance of reactive oxygen metabolites in placenta,
      abnormal trophoblast invasion, disorders of lipoprotein metabolism and signal
      transduction, or some that have been reported to have close correlation to the
      pathology of pre-eclampsia. The microarray data were also confirmed by the
      measurement of real-time PCR. CONCLUSION: DNA microarray is a high throughput and
      time-saving method to monitor altered gene expression. The results could provide
      interesting clues to the etiology of pre-eclampsia and lead to further studies in
      a more targeted fashion.

PMID- 16651851
TI  - The current and future state of interventional cardiology: a critical appraisal.
AB  - After 75 years of invasive and over 50 years of interventional cardiology,
      cardiac catheter-based procedures have become the most frequently used
      interventions of modern medicine. Patients undergoing a percutaneous coronary
      intervention (PCI) outnumber those with coronary artery bypass surgery by a
      factor of 2 to 4. The default approach to PCI is the implantation of a (drug
      eluting) stent, in spite of the fact that it improves the results of balloon
      angioplasty only in about 25% of cases. The dominance of stenting over
      conservative therapy or balloon angioplasty on one hand and bypass surgery on the
      other hand is a flagrant example of how medical research is digested an applied
      in real life. Apart from electrophysiological interventions, closure ot the
      patent foramen ovale and percutaneous replacement of the aortic valve in the
      elderly have the potential of becoming daily routine procedures in
      catheterization laboratories around the world. Stem cell regeneration of vessels
      or heart muscle, on the other hand, may remain a dream never to come true.

PMID- 16651852
TI  - Detection of human chorionic gonadotrophin-beta in serum or urine of prostate
      cancer patients is of no clinical significance.
AB  - The aim of this study was to prospectively evaluate the potential role of
      elevated urinary/serum human chorionic gonadotrophin-beta (hCGbeta) in prostate
      cancer prognosis. 104 patients with newly diagnosed prostate cancers were
      included; 68 patients had organ-confined, 18 had locally advanced and 18 had
      metastatic disease. A control group consisted of 115 patients presenting with
      benign prostatic disease. Serum and urinary total hCGbeta was measured prior to
      treatment and serum PSA was measured at diagnosis. The patients were treated
      along conventional lines and progression-free survival was assessed. Four
      patients had elevated serum and 10 had elevated urinary, total hCGbeta. There
      were no significant correlations between serum/urinary levels of hCGbeta and
      tumour stage, Gleason score or PSA. In contrast, serum PSA had significant linear
      correlations with both clinical tumour stage and Gleason score (p = 0.0001). At a
      median follow-up of 36 months, 22 (21.2%) patients had died while 17 (16.3%)
      others had progressed. Kaplan-Meier plots and log-rank test revealed no
      significant difference in progression-free survival between patients with
      elevated or normal levels of serum and/or urinary total hCGbeta. Clinical tumour
      stage, grade and PSA were statistically significant prognostic variables.
      Immunoassay measurement of serum or urinary hCGbeta has no significant role in
      the clinical management of prostate cancer.

PMID- 16651853
TI  - Elevated serum soluble CD30 precedes the development of AIDS-associated non
      Hodgkin's B cell lymphoma.
AB  - CD30, first described as the Ki antigen on malignant B cells in Hodgkin's
      lymphoma, is also expressed on normal activated B and T cells. It can be cleaved
      from the cell surface and detected in normal serum as soluble CD30 (sCD30), where
      it can be an indicator of levels of immune activation. In a cross-sectional study
      utilizing archived sera at a time point close to but preceding a diagnosis of
      acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's B cell
      lymphoma, AIDS lymphoma subjects (n = 49) showed elevated mean levels of sCD30
      compared to controls with AIDS but no malignancy (n = 44, p < 0.01), HIV-infected
      but relatively healthy (n = 47, p < 0.001), or HIV-seronegative controls (n = 44,
      p < 0.001). Serum sCD30 was significantly correlated to serum levels of the B
      cell cytokines interleukin-6 (IL-6), IL-10, and sCD23, but only among lymphoma
      subjects (p < or = 0.05). Correlations between sCD30 and other markers of immune
      system activation were seen among all HIV-infected subjects (sCD27, sCD44,
      CXCL13, p < 0.05). These observations suggest that sCD30, especially in
      combination with other immune system molecules, could be an important biomarker
      for an immune system environment conducive to B cell hyperactivation and the
      development of AIDS-associated B cell lymphoma.

PMID- 16651854
TI  - Effects of HER2-binding affibody molecules on intracellular signaling pathways.
AB  - BACKGROUND: HER2, which is overexpressed in 25-30% of human breast cancers, is a
      tyrosine kinase receptor critical for the signal transduction network that
      regulates proliferation, migration and apoptosis of cells. METHOD: We report the
      effects of two novel HER2-binding affibody molecules (Affibody), (ZHER2:4)2 and
      ZHER2:342, on intracellular signal transduction pathways (Erk1/2, Akt and
      PLCgamma1) using quantitative immunoblotting techniques and their biological
      effects in cell culture. The clinically approved antibody trastuzumab (Herceptin)
      was used as reference substance. RESULTS: Our data showed that, although all
      substances target HER2, the effects on the receptor and signaling molecules
      differed. For example, HER2 phosphorylation was induced by trastuzumab and
      (ZHER2:4)2 but inhibited by ZHER2:342. The effects these substances had on signal
      transduction correlated to some degree with changes in growth and migration, e.g.
      (ZHER2:4)2 stimulated phosphorylation of Erk1/2 and PLCgamma1, as well as growth
      and migration, while ZHER2:342 did not. ZHER2:342 even inhibited phosphorylation
      of PLCgamma1 and migration. CONCLUSION: Our data suggest that ZHER2:342 is a
      promising small agent (7 kDa) that may be used as an alternative, or complement,
      to trastuzumab. If radiolabelled, it can hopefully also be used for HER2 imaging
      and radionuclide therapy.

PMID- 16651856
TI  - Quality councils as health system performance and accountability mechanisms: the
      Cancer Quality Council of Ontario experience.
AB  - Recent national and provincial reviews on the status of healthcare in Canada have
      recommended the establishment of quality councils to guide quality improvement
      efforts. The emergence of quality councils, such as the Health Quality Council of
      Alberta, the Saskatchewan Health Quality Council, the Cancer Quality Council of
      Ontario and the Health Council of Canada, reflect new but largely unscrutinized
      models for improving quality of care. We discuss the varying mandates of these
      new quality councils, their fit with evolving governance and accountability
      structures and the credibility and legitimacy of their role as perceived by other
      health system organizations. To further illustrate these issues, we present
      insiders' perspectives on the Cancer Quality Council of Ontario's activities over
      its first three years, including the initial agenda, critical success factors and
      the nature of evolving relationships with other organizations in Ontario's
      healthcare system. While current Canadian quality councils represent an eclectic
      mix of methods for achieving improvements in quality of care, it is not entirely
      clear how quality councils will stimulate sustained and significant improvements
      in quality of care where other models have failed. However, these new Canadian
      quality councils represent natural experiments in motion from which much needs to
      be learned.

PMID- 16651857
TI  - The role of safety and quality councils in improving the quality of healthcare:
      an Australian perspective.
AB  - The Australian Council for Safety and Quality in Health Care (the Council) has
      made considerable advances in gaining acceptance of and commitment to the
      healthcare safety improvement agenda by all involved in healthcare in Australia.
      It has provided a focus for national efforts in safety and quality improvement,
      by raising awareness, building consensus and clarifying areas for priority
      action. While the Council has set the agenda for change and provides advice in
      relation to problems, initiatives and actions, it has limited operational
      capacity and lacks the statutory authority to embed a culture of safety at all
      levels of the healthcare system. Statutory and regulatory responsibility and
      accountability for implementation lies with the Australian, State and Territory
      Governments and organizations in the private sector. Progress depends on
      coordinating the activities of Departments of Health and Human Services of nine
      sovereign governments. The "levers for change" available to the Council were
      leadership, persuasion, advice and example, with the ability to develop
      strategies, frameworks, standards, tools and guidelines. With the end of the
      Council's term approaching, a recent review recommended the establishment of an
      Australian Commission on Safety & Quality in Health Care (the Commission).

PMID- 16651858
TI  - Citizens' quality councils: an innovative mechanism for monitoring and providing
      social endorsement of healthcare providers' performance?
AB  - In recent years, under the influence of continuing improvement and total quality
      strategies, efforts to improve the quality of healthcare have been generated from
      within each healthcare organization. External mechanisms, such as accreditation,
      that drive quality improvement from without, have existed for much longer.
      However, these accreditation systems incorporated the need to demonstrate the
      existence of continuing improvement processes as a standard barely 10 years ago;
      thus, the external mechanism included the development of internal processes as
      yet another requirement. As Dobrow, Langer, Angus and Sullivan state in the lead
      article, the existence of a whole evidence-based culture that has spread the
      concern about quality is beyond doubt; I would add that it has also intensified
      this concern. Several factors have contributed to this trend, which now seems
      irreversible. On the one hand, as the paper points out, one of these factors is
      the growing requirement to allocate resources according to performance. On the
      other, there is the growing evidence of errors committed by health systems that
      cause harm to patients. The latter has created increasing demand for reliable
      information, conceived not only to allow the detection of these situations, but
      also to invest greater reliability in the health systems in the eyes of patients
      and general public. In both cases, however, the question remains: Who defines and
      who measures quality levels in such a way that the information is credible?

PMID- 16651859
TI  - Quality councils as catalysts and leaders in quality improvement: the experience
      of the health quality council in Saskatchewan.
AB  - Quality councils are an increasingly common phenomenon in Canada. The Health
      Quality Council in Saskatchewan, the largest such council in Canada, is similar
      to other councils in that it reports publicly on quality of care, but it differs
      in that it has an explicit, central role to support quality improvement
      activities. The HQC strives to gain buy-in and cooperation from provider groups,
      even those identified as having suboptimal care, by offering them quality
      improvement training, measurement tools, information about best practices and
      advice from experts in change management, group psychology, process redesign and
      operations research. Developing relationships with stakeholders is a very labour-
      intensive process, but it is essential to fostering a blame-free culture of
      quality improvement. The HQC works with senior leaders to help coordinate
      province-wide priorities for quality improvement and with middle managers and
      frontline staff to establish local quality improvement teams. It does not alter
      the structure of existing accountability relationships; rather, it tries to make
      the dialogue more quality-focused. Its largest-scale activity is a Learning
      Collaborative involving 20% of all family physicians in the province in an effort
      to improve chronic disease management. The HQC believes that these targeted,
      coordinated activities in quality improvement will ultimately be far more
      effective than simply releasing reports or making recommendations.

PMID- 16651860
TI  - Enhancing quality improvement.
AB  - The healthcare systems of most developed nations face a common challenge: a
      substantial gap exists between the best possible care and the care routinely
      delivered. Numerous studies in the literature and reports from authoritative
      bodies, such as the Institute of Medicine (IOM) in the United States, have
      provided compelling and persuasive evidence that care is not consistently safe,
      timely, effective, equitable, efficient or patient-centred. A landmark study
      published in 2003 reported that Americans receive recommended care 54.9% of the
      time (McGlynn et al. 2003). The recent survey conducted by the Commonwealth Fund
      of sicker adults in six countries - Australia, Canada, Germany, New Zealand, the
      United Kingdom and the United States - underscores the pervasive challenges of
      providing high-quality care. The differences between the six countries pale in
      contrast to the common theme of significant opportunities for improvement in all
      nations (Schoen et al. 2005).

PMID- 16651861
TI  - Quality councils as change agents and drivers of quality improvement in
      healthcare.
AB  - This commentary addresses four key questions raised in the lead paper. We
      recognize that health quality councils have a delimited range of tools available
      to bring about needed change. They have neither funding and regulatory powers nor
      day-to-day operational authority. Nevertheless, based on the Health Quality
      Council of Alberta's (HQCA) successes to date using a multidimensional change
      strategy, we are confident that quality councils can play a vital role in driving
      and sustaining quality improvement in provincial healthcare systems. The provisos
      are that the councils need to be sufficiently empowered, establish themselves as
      trusted partners and independent advisors, use effective change strategies, focus
      on strategic priorities and gain strong stakeholder support for needed changes.
      We are also convinced that multilevel measurement is an essential tool for
      learning, priority setting, establishing the imperative for action and assessing
      progress. Finally, in terms of the value proposition - the relationship between
      resource inputs and healthcare outcomes - we strongly suggest that health quality
      councils work collaboratively with service providers to obtain better value for
      money by improving quality rather than aligning themselves with funders and rely
      on "pay for quality" incentives to "compel" quality improvement.

PMID- 16651863
TI  - Physiopathology of catalytic antibodies: the case for factor VIII-hydrolyzing
      immunoglobulin G.
AB  - Antibodies that are able to catalyze the antigen for which they are specific are
      produced spontaneously by the immune system. Catalytic immunoglobulins (Igs) both
      of the IgM and IgG isotypes have been detected in the serum of healthy donors,
      where they have been proposed to participate in the removal of metabolic waste
      and in the defense of the organism against invading pathogens. Conversely,
      antigen-specific hydrolytic IgG have been reported in a number of inflammatory,
      autoimmune and neoplastic disorders: their pathogenic effects have been
      demonstrated occasionally. The pathophysiological relevance of catalytic
      antibodies thus remains an elusive issue. Through the description of the pro
      coagulation factor VIII as a model target antigen for catalytic antibodies, we
      propose that catalytic antibodies have either a beneficial or a deleterious role
      depending on the physiopathological context. Physiology thus relies on a delicate
      equilibrium between the levels of soluble target antigen and that of antigen
      specific hydrolyzing immunoglobulins. Indeed, in patients with hemophilia A, in
      whom endogenous factor VIII is deficient or missing and exogenous factor VIII
      needs to be administered to treat hemorrhagic events, the development of factor
      VIII-hydrolyzing IgG that inactivate the therapeutically administered factor
      VIII, may reveal deleterious. In contrast, in a situation in which excess factor
      VIII may be detrimental and lead to excessive coagulation, disseminated
      thrombosis and organ ischemia, as seen in severe sepsis, our recent data suggest
      that the presence of factor VIII-hydrolyzing IgG may be beneficial to the
      patient.

PMID- 16651864
TI  - Inherited abnormalities of fibrinogen: 10-year clinical experience of an Italian
      group.
AB  - Inherited abnormalities of fibrinogen present a high variability in penetrance
      and expressivity, and clinical manifestations vary from severe bleeding or
      thrombosis to asymptomatic This variability makes clinical and genetic counseling
      more difficult. We report the experience of a clinical group working in
      specialist centers in Southern Italy on a series of consecutive patients
      presenting with congenital abnormalities of fibrinogen. Over 10 years, 18
      patients were diagnosed to carry a congenital abnormality of fibrinogen. These
      patients and 26 first-degree relatives were investigated in-depth to fully
      characterize the nature of their abnormal fibrinogen levels. A gene mutation was
      identified in 15 patients (four afibrinogenemic patients, three
      hypofibrinogenemic patients, and eight dysfibrinogenemic patients). A new
      mutation was found in four of them: Aalpha Arg159Stop in one afibrinogenemic
      patient, Aalpha Arg104Cys in two hypofibrinogenemic patients, and Aalpha
      Pro270Thr in one dysfibrinogenemic patient. While all afibrinogenemic patients
      had clinically important bleeding, participants presenting with
      hypofibrinogenemia remained asymptomatic. In the presence of the synthesis of an
      abnormal molecule, the clinical phenotype was not strictly related to plasma
      fibrinogen levels but was associated with the molecular defect, most carriers
      remaining asymptomatic. Personal and family histories of bleeding and thrombosis
      are important for the clinical management of patients presenting with congenital
      abnormalities of fibrinogen. Biochemical and genetic investigations may be a
      useful guide for decision-making, providing additional steps in the assessment of
      the risk of patients presenting with low levels of a normal molecule
      (hypofibrinogenemia and afibrinogenemia) and with an abnormal molecule
      (dysfibrinogenemia), respectively.

PMID- 16651865
TI  - Recombinant activated factor VIIa in uncontrolled bleeding: a haemostasis
      laboratory study in non-haemophilia patients.
AB  - Extensive surgery and massive tissue trauma are often associated with severe
      bleeding. We present retrospective data on the use of recombinant factor VIIa in
      haemostatic emergencies in13 non-hemophilia patients with uncontrolled bleeding.
      Recombinant factor VIIa was administered in doses ranging from 16 mug/kg
      bodyweight to 60 microg/kg bodyweight. Blood loss during 24 h before and after
      the infusion was registered, showing that 10 out of 13 patients (77%) had a 70%
      or greater reduction in transfusion requirement decreasing significantly in mean
      from 28.1 to 9.9 red blood cell units. Coagulation parameters were studied in
      blood samples collected 10 min before and 10-15 min after the injection of
      recombinant factor VIIa. Factors VII:C, II:C, and X:C increased significantly
      while the activated partial thromboplastin time, platelet numbers, and
      concentration of fibrinogen and D-dimers were unchanged. The dose of rFVIIa
      correlated significantly with the rise in factor X:C and inversely with
      transfusion requirements. Dynamic clot velocity of whole blood was recorded
      before and after rFVIIa infusion in four patients. Judged from red blood cell
      usage no improvement in haemostasis was seen in one patient suffering
      thrombocytopenia and low fibrinogen. This patient died 6 h after recombinant
      factor VIIa infusion, and three other patients died before 1 month. None of the
      fatalities appeared to be related to recombinant factor VIIa usage. No
      thromboembolic complications were seen. In conclusion, 12 out of 13 patients
      survived the first 24 h after treatment with relatively low doses of recombinant
      factor VIIa for large-scale bleeding. Recombinant factor VIIa was well tolerated
      and safe in these non-hemophilia patients. With quite low doses of recombinant
      factor VIIa (<or= 60 microg/kg), the dose of recombinant factor VIIa correlated
      positively with efficacy. Activation of factor X appeared to predict haemostatic
      efficacy.

PMID- 16651866
TI  - Factor XI enhances fibrin generation and inhibits fibrinolysis in a coagulation
      model initiated by surface-coated tissue factor.
AB  - In-vitro studies have shown that thrombin-mediated factor XI activation enhances
      thrombin and fibrin formation, rendering the clot more thrombogenic and
      protecting it from lysis by activation of thrombin activatable fibrinolysis
      inhibitor. These effects of factor XI are only observed when coagulation is
      initiated by a low concentration of soluble tissue factor. At high concentrations
      of soluble tissue factor no effects of factor XI are seen on coagulation and
      fibrinolysis. In vivo, tissue factor is present in large amounts in the vascular
      wall. This makes it difficult to extrapolate these in-vitro findings on factor XI
      to the in-vivo situation. To address the question of whether factor XI could play
      a role in coagulation initiated on a tissue factor-containing surface we devised
      a static in-vitro coagulation model in which clotting is initiated in recalcified
      citrated plasma by tissue factor coated on the bottom of microtiter plates. The
      effect of factor XI was studied with an antibody that blocked the activation of
      factor IX by activated factor XI. The tissue factor coating strategy produced
      clotting times similar to those obtained with cultured tissue factor-expressing
      vessel wall cells (smooth muscle cells, fibroblasts and activated endothelial
      cells) grown to confluence in the same wells. A factor XI-dependent effect on
      clot formation and clot lysis was observed depending on the plasma volume used.
      In clots formed from small amounts of plasma (100 microl) no effect of factor XI
      was detected. In larger clots (200-300 microl) factor XI not only increased
      prothrombin activation and the fibrin formation rate but also inhibited
      fibrinolysis. Effects of factor XI were observed at short clotting times (3-4
      min) similar to the clotting times found on cultured tissue factor-expressing
      vessel wall cells. This is in contrast with earlier studies using soluble tissue
      factor, in which effects of factor XI were only observed at much longer clotting
      times using low soluble tissue factor concentrations. We conclude that factor XI
      not only enhances coagulation initiated by surface bound tissue factor but also
      protects the clot against lysis once it is formed. On the basis of these results,
      we propose a coagulation model in which initial clot formation in the proximity
      of the tissue factor surface is not factor XI dependent. Clot formation becomes
      dependent on factor XI in the propagation phase when the clot is increasing in
      size. These findings support a role for factor XI in the propagation of clot
      growth after tissue factor-dependent initiation.

PMID- 16651867
TI  - Inhibitory effects of cardiotonic pills on platelet function in dogs fed a high
      fat diet.
AB  - Insulin resistance and the consequent metabolic disorders are associated with a
      state of platelet hyperactivity. Oxidative stress is responsible for the
      persistent platelet activation. We sought to study the inhibitory effect of
      cardiotonic pills, an oral herbal component, on platelet function in a dog model
      with insulin resistance induced by high-fat feeding. We fed 18 dogs with a high
      fat diet and six dogs with normal chow as control for 6 months. Then, six dogs
      were fed with a high-fat diet and received additional aspirin (250 mg/day), and
      another six dogs received additional cardiotonic pills (1,000 mg/day) for 4
      months. Time-course changes in metabolic parameters and platelet function were
      detected. After high-fat feeding for 6 months, 18 dogs developed a series of
      metabolic disorders including obesity, dyslipidemia, oxidative stress and insulin
      resistance. In addition, a platelet hyperactivity state, characterized by
      increased agonist (arachidonic acid, ADP and collagen) induced platelet
      aggregation, platelet expression of adhesion molecules (P-selectin and GP
      IIb/IIIa), and platelet intracellular calcium concentration, was indicated.
      Cardiotonic pills showed a significant antioxidative activity by presenting an
      increase in plasma superoxide dismutase and decrease in erythrocyte glutathione,
      as well as a lipid-lowering effect (decrease in both plasma cholesterol and
      triglyceride). Either aspirin or cardiotonic pills could significantly reverse
      the platelet hypersensitivity and hyperfunction. Compared with aspirin,
      cardiotonic pills showed a more exaggerated inhibitory effect on platelet
      function (a significantly decreased collagen-stimulated platelet aggregation, and
      expression of adhesion molecules). In conclusion, cardiotonic pills inhibited
      platelet hyperfunction in dogs with insulin resistance. This inhibitory effect
      may mainly be explained by antioxidative activity and metabolic control.

PMID- 16651868
TI  - Risk factors associated with venous thromboembolic events in patients with
      malignancy.
AB  - Malignancy is a major risk factor for venous thromboembolic events, but not all
      patients with malignancy develop such events. This study attempts to identify
      risk factors in patients with malignancy who develop venous thromboembolic
      events. In the current study, 566 consecutive patients without venous
      thromboembolic events and 416 patients with, admitted to University of Michigan
      with malignancy between 1992 and 2000, were identified using International
      Classification of Diseases-9 Clinical Modification codes. Data on potential risk
      factors was obtained from the University of Michigan Cancer Registry and the
      medical record. Univariate and multivariate analysis was used to identify factors
      associated with venous thromboembolic events and mortality. The mean patient age
      was 45.6 years with a mean survival of 7.8 years from cancer diagnosis. Venous
      thromboembolic events were associated with solid tumors (odds ratio 5.0; 95%
      confidence interval 1.7-14.9; P = 0.004), infection (4.9; 1.2-19.8; P = 0.03),
      and increasing age (1.05; 1.03-1.08; P < 0.001). While leukopenia (4.2; 1.2-14.6;
      P = 0.02) was associated with an increased incidence of venous thromboembolic
      events, neutropenia was not. Sex, type of therapy, and cancer stage were not
      independently associated with venous thromboembolic events. Survival was
      decreased in patients with venous thromboembolic events (5.9 versus 9.2 years, P
      < 0.0001). Solid tumors (3.9; 1.8-8.4; P = 0.001), infection (3.3; 1.1-9.9; P =
      0.03), advanced stage (1.6; 1.2-2.1; P = 0.001), and increasing age (1.02; 1.0
      1.04; P = 0.01) were associated with decreased survival. Patients with malignancy
      who have solid tumors, advanced age, infection, and leukopenia have a
      significantly increased risk of venous thromboembolic events.

PMID- 16651869
TI  - Factor V Leiden and increased risk for arterial thrombotic disease in young
      Brazilian patients.
AB  - The contribution of mutations in the prothrombin (FII G20210A),
      methylenetetrahydrofolate reductase (C677T) genes and factor V Leiden (FVL) to
      the pathogenesis of arterial thrombosis remains controversial. In this study,
      these polymorphisms were investigated by polymerase chain reaction-restriction
      fragment length polymorphism in a group of 53 patients that presented arterial
      thrombosis other than myocardial infarction as a first thrombotic event and 275
      control subjects living in the state of Minas Gerais, Brazil. Odds ratio (OR) and
      chi tests were applied for statistical comparisons. Similar frequencies were
      detected among patients and control subjects for the C677T mutation. The 20210A
      mutation was present in 3.6% of the control subjects but was not detected among
      ischemic stroke patients. Significant differences were detected only for factor V
      Leiden (odds ratio 7.11; 95% confidence interval 1.55-32.73). Our data indicate
      that, among these genetic factors, factor V Leiden was identified as an important
      risk factor for arterial thrombosis in this group of patients. In addition, our
      results indicate regional differences in the incidence of these genetic factors
      in Brazil, as compared to the incidences reported in other studies.

PMID- 16651870
TI  - Effect of native fucoidan, sulfated fucoidan, heparin and 6-aminohexanoic acid on
      the activation of glutamic-plasminogen by urokinase: role of NaCl.
AB  - Addition of a physiological concentration of NaCl (0.9%) to 0.05 mol/l Tris
      buffer (pH 7.4) reversed the enhancement of the activation of glutamic-type
      plasminogen (Glu-Plg) by low molecular weight urokinase by fucoidan and heparin,
      while addition of aminohexanoic acid (6-AH) enhanced the activation. Native
      fucoidan (N-2), sulfated fucoidan (S-2) and heparin alone and in the presence of
      6-AH were investigated to determine the effect of NaCl addition to 0.05 mol/l
      Tris (pH 7.4) on the activation of Glu-plg by high molecular weight urokinase
      (HMW u-Pa). Heparin alone and in conjunction with 6-AH enhanced 4.5 to 5.5-fold
      the initial rate of activation of Glu-plg, while N-2 alone or in conjunction with
      6-AH gave 3 to 5.5-fold enhancement and S-2 gave no enhancement of activation
      using 0.05 mol/l Tris buffer (pH 7.4). Addition of 0.9% NaCl to the buffer
      reversed the enhancement by the cofactors but, in the presence of 6-AH, N-2 gave
      two-fold and S-2 gave three-fold enhancement of activation while heparin gave 25%
      enhancement. The mechanism of enhancement by S-2 in the presence of 6-AH was
      investigated by dilution and enzyme kinetic studies. The results show that the
      enhancement was due to interaction with HMW u-PA and not with Glu-plg.

PMID- 16651871
TI  - Molecular cloning and functional expression of rabbit alpha2-antiplasmin.
AB  - The rabbit is frequently employed in small animal models of in-vivo coagulation
      and fibrinolysis, but the degree to which its plasma proteins resemble their
      human counterparts is incompletely known. Our aims were: to determine the
      nucleotide sequence of a full-length rabbit liver alpha(2)-antiplasmin
      (alpha(2)AP) cDNA; compare it with its human, murine, and bovine counterparts;
      and express it in functional form. Partial cDNAs encoding 5' and 3' portions of
      the alpha(2)AP mRNA were obtained by reverse transcriptase (RT)-polymerase chain
      reaction (PCR), using rabbit liver RNA and 'guessmer' oligonucleotides based on
      known sequences. This information was employed to design additional
      oligonucleotides for RT-PCR and rapid amplification of cDNA ends (RACE)
      procedures yielding overlapping clones corresponding to the entire rabbit
      alpha(2)AP mRNA sequence. Mature alpha(2)AP was expressed as a hexahistidine
      tagged recombinant protein in Escherichia coli, purified by nickel-chelate
      affinity and ion exchange chromatography, and its reaction with plasmin and
      soluble fibrin assessed electrophoretically and compared with an analogous
      recombinant human alpha(2)AP. The consensus rabbit alpha(2)AP cDNA is 2,157 bp
      long, and encodes a 464-residue mature sequence and a 27-amino-acid presequence.
      The mature protein is 82% identical to its human counterpart, and its recombinant
      form produced denaturation-resistant complexes with both plasmin and fibrin. The
      region of greatest sequence divergence lies within the C-terminal extension of
      alpha(2)AP, unique in the serpin family of proteins to which alpha(2)AP belongs.
      The highly conserved nature of rabbit alpha(2)AP reinforces its role as a vital
      antifibrinolytic protein and supports fibrinolytic investigations in models
      employing this small animal.

PMID- 16651872
TI  - Folate deficiency induced hyperhomocysteinemia changes the expression of
      thrombosis-related genes.
AB  - Hyperhomocysteinemia (HH) is an independent risk factor for thrombosis although
      the precise pathogenesis is still unresolved. Previous studies have demonstrated
      that HH changes whole blood coagulation by increasing the velocity, increasing
      the firmness of the formed clot, and by prolonging the initiation phase of the
      coagulation. With the aim of elucidating the genetic pathogenesis which might be
      responsible for the changes in whole blood coagulation, we applied oligo-array
      technology to RNA from buffycoat-cells comparing animals suffering from
      hyperhomocysteinemia (42 micromol/l) with controls (6 micromol/l). Data mining
      identified a number of relevant genes, and the expression pattern was validated
      by real time reverse transcriptase-polymerase chain reaction. An upregulation of
      integrin beta-3, Rap 1b, glycoprotein V, platelet-endothelial cell adhesion
      molecule-1 (PECAM-1) and von Willebrand factor (vWF) led us to deduce increased
      platelet activation/aggregation. Coagulation factor XIIIa was upregulated and may
      contribute in increasing the firmness of the formed clot. Impaired fibrinolysis
      was anticipated, since an upregulation of plasminogen activator inhibitor-1 (PAI
      1) and a downregulation of tissue-type plasminogen activator (t-PA) were
      detected. Reduced spontaneous contact activation was anticipated due to a
      downregulation of the kallikrein gene. Upregulation of selectins may contribute
      to increased tethering and rolling of leukocytes. In conclusion, folate
      deficiency induced hyperhomocysteinemia changes in the gene expression of buffy
      coat cells which was characterized by increased platelet activation, impaired
      fibrinolysis and a reduced contact activation of the coagulation. These changes
      may contribute to explain the increased risk of thrombosis seen in
      hyperhomocysteinemia individuals. This pattern of the hyperhomocysteinemia
      affected genes may represent a reference for further studies at the protein level
      to define the folate depletion effects in blood cells.

PMID- 16651873
TI  - D-dimer is not a long-term prognostic marker following acute cerebral ischemia.
AB  - Recent evidence indicates a possible role of D-dimer in the early diagnosis of
      ischemic stroke subtypes. Whether D-dimer can also predict the long-term outcome
      following ischemic stroke is controversial. To define the prognostic role of D
      dimer, patients hospitalized after an acute ischemic cerebrovascular event
      underwent D-dimer measurement (Liatest D-D; normal level < 0.50 microg/ml) on
      admission and were followed up for recurrent cerebrovascular events, occurrence
      of other cardiovascular events, and mortality. We enrolled 96 patients (mean age
      74.9 years, 42 men). Mean follow-up was 61.5 months; 47 (48.5%) patients died, 23
      (48.9%) because of a vascular event. There was no difference in mean D-dimer
      levels between dead patients and survivors (1.68 and 1.63 microg/ml, P = NS), but
      the mortality risk was higher with D-dimer of at least 0.50 microg/ml (odds
      ratio, 5.32; 95% confidence interval, 1.79-15.84). After adjustment for age and
      stroke subtype, the odds ratio was not significant. Mean D-dimer was similar
      between patients with and without a new vascular event (1.43 and 1.68 microg/ml,
      P = NS), and D-dimer of at least 0.50 microg/ml was not predictive of an
      increased risk of subsequent events. D-dimer levels measured in the acute phase
      after an acute cerebrovascular event probably do not predict the long-term
      clinical outcome.

PMID- 16651874
TI  - Role of interleukin-6 in fibrinolytic changes induced by lipopolysaccharide in
      mice.
AB  - We have recently demonstrated that interleukin (IL)-6 is protective against
      coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage
      induced by bacterial endotoxin, at least partly, via the inhibition of
      proinflammatory cytokines and chemokines using IL-6-null [IL-6(-/-)] mice and
      corresponding wild-type mice. Its role in fibrinolytic systems remains undefined,
      however. The present study elucidated the role of IL-6 in the activity of
      alpha(2)-plasmin inhibitor, an inhibitor of fibrinolysis, during inflammation
      induced by intraperitoneal administration of lipopolysaccharide in IL-6(-/-) and
      wild-type mice. Both IL-6(-/-) and wild-type mice were injected with vehicle or
      lipopolysaccharide (1 mg/kg). Seventy-two hours later, blood samples were
      collected and alpha(2)-plasmin inhibitor activity was examined.
      Lipopolysaccharide challenge induced significant enhancement of alpha(2)-plasmin
      inhibitor activity as compared with vehicle challenge in wild-type mice, but not
      in IL-6(-/-) mice. In the presence of lipopolysaccharide, the activity was
      significantly lower in IL-6(-/-) mice than that in wild-type mice. These results
      indicate that IL-6 can, at least partly, inhibit the lipopolysaccharide-enhanced
      fibrinolysis via the enhanced alpha2-plasmin inhibitor activity.

PMID- 16651875
TI  - The use of recombinant-activated factor VII in von Willebrand disease: a case
      series.
AB  - Spontaneous and surgery-associated bleeding in patients with von Willebrand
      disease (vWD) cannot always be controlled with desmopressin or replacement
      therapy. This paper presents results on the use of recombinant-activated factor
      VII (rFVIIa) in patients with vWD included in the internet registry
      Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified
      from the database and included in this analysis. The bleeding episodes were
      classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were
      unspecified in three cases. The median dose of rFVIIa administered was 94
      microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27
      evaluable patients (85%) and markedly decreased in three patients; the total
      response rate was 96% (26/27 patients). Response did not correlate with the type
      of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other
      replacement therapies were infrequently used, and their use was similar in the 24
      h before and after rFVIIa administration. Eighteen patients also received
      antifibrinolytic treatment, but its impact on response was not recorded. Only one
      adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as
      a safe and effective therapy for vWD.

PMID- 16651876
TI  - Use of recombinant activated factor VII to control bleeding in a young child with
      qualitative platelet disorder: a case report.
AB  - Defects of platelet adhesion, aggregation, secretion, or procoagulant activities
      can lead to bleeding diathesis of variable severity. We used recombinant
      activated factor VII (rFVIIa) in the treatment of uncontrolled epistaxis in a
      patient with a qualitative platelet disorder. We aimed to assess the efficacy of
      a single rFVIIa dose (100 microg/kg) in the control of mild and severe refractory
      epistaxis, and evaluate the influence of rFVIIa on markers of platelet adhesion
      and aggregation during a period of hematological stability (i.e. non-bleeding, no
      medication). The efficacy study showed mild episodes of epistaxis could be
      successfully managed using a single rFVIIa (100 microg/kg) dose; however, severe
      bleedings were not well controlled, and platelet transfusion was required to
      achieve hemostasis. Hematological investigations showed ADP-induced and collagen
      induced platelet aggregation increases from 20 to 34% and 16 to 30%,
      respectively, following rFVIIa administration. There were no differences between
      pre-dose and post-dose concentrations of membrane glycoproteins. rFVIIa may
      therefore induce platelet aggregation by activating a glycoprotein-independent
      aggregation pathway. rFVIIa may have a role in managing mild bleeding episodes
      not controlled using conventional measures in patients with a qualitative
      platelet disorder. Further research is needed to determine the mechanism of
      action, efficacy, and safety of rFVIIa in this population.

PMID- 16651877
TI  - Recombinant activated factor VII for severe uterine bleeding after chemotherapy
      in a woman with acute myeloid leukemia.
AB  - Acute hemorrhage is sometimes a serious complication that may arise in patients
      with acute leukemia as a result of therapy-induced myelosuppression. In most
      cases, transfusion of platelets and red blood cells are used to manage this
      clinical entity. These therapeutic interventions are not always successful and a
      more direct approach to activating the coagulation system can be more effective
      and, in some instances, life saving. Recombinant activated factor VII (rFVIIa),
      which is used for management of hemophiliac patients with inhibitors, is a major
      alternative in such situations. Here we describe the use of rFVIIa in a 41-year
      old patient with ongoing vaginal bleeding with acute myeloid leukemia. Our
      experience indicates that rFVIIa may be an effective salvage treatment in
      bleeding conditions related to leukemia.

PMID- 16651878
TI  - Efficacy of desmopressin in preventing hemorrhagic complications in a patient
      with Marfan syndrome undergoing cardiac surgery.
AB  - In this case report, we describe the successful use of desmopressin as
      prophylaxis against hemorrhage in a patient with a bleeding tendency associated
      with Marfan syndrome and a platelet function defect undergoing cardiovascular
      surgery.

PMID- 16651879
TI  - Successful treatment of massive acute lower gastrointestinal bleeding in
      diverticular disease of colon, with activated recombinant factor VII (NovoSeven).
AB  - Recombinant coagulation factor (rFVIIa) (NovoSeven; Novo Nordisk A/S, Copenhagen,
      Denmark) is registered in most regions in the world for the treatment of bleeding
      episodes in haemophilia with inhibitors to factor VIII or factor IX. The
      mechanism of action suggests that its enhancing effects in haemostasis are
      limited to the site of injury and that systemic activation of the coagulation
      cascade does not occur. We report a case of lower gastrointestinal bleeding in
      diverticular disease of the colon in an inoperable elderly patient without pre
      existing coagulopathy, which has successfully treated with a single injection of
      rFVIIa. This experience suggests that rFVIIa, besides its actual high costs,
      might be a useful and safe, noninvasive therapeutic tool in selected cases of
      massive lower gastrointestinal bleeding in the elderly.

PMID- 16651880
TI  - Bivalirudin for anticoagulation in mechanical aortic valve replacement and
      heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially serious syndrome. Since
      there are some alternatives to treatment with heparin in patients who develop
      HIT, the decision as to which to use should be based on renal and hepatic
      function, drug availability and the available monitoring resources. We report a
      patient who received heparin for mechanical aortic valve replacement. Her
      clinical course was complicated by HIT, which was treated initially by
      danaparoid. The syndrome progressed with new thrombotic complications, and
      eventually was treated successfully by bivalirudin (Angiomax; Medison Pharma Ltd,
      Petach Tikva, Israel) for 9 days. We propose that treatment with bivalirudin for
      several days is a safe and effective alternative to heparin therapy in patients
      who develop HIT.

PMID- 16651881
TI  - Microglia in the aging brain.
AB  - The aging brain is characterized by a demonstrable decrease in weight and volume,
      particularly after the age of 50. This atrophy, which affects both grey and white
      matter, is presumed to result from a loss of neurons and myelinated axons. Glial
      cells, on the other hand, appear to increase in the aging brain, which exhibits
      greater immunoreactivity with both astrocytic and microglial markers. This review
      is focused on the morphologic and phenotypic changes that occur in microglial
      cells with normal aging. Although there is a consistent aging-related
      upregulation of microglial activation markers in experimental animals and humans
      that could be interpreted as aging-related neuroinflammation, it is generally
      difficult to show a direct correlation between ostensible microglial activation
      and neurodegeneration. This raises questions about whether aging-related
      microglial activation indeed represents reactive gliosis in the conventional
      sense. As an alternative, we discuss the possibility that structural and
      phenotypic changes that occur in microglia are a direct reflection of the aging
      process on microglia. Thus, microglia cells themselves may be subject to cellular
      senescence in the sense that they no longer function efficiently. The concept of
      microglial senescence offers a novel perspective on aging-related
      neurodegeneration, namely that neurodegeneration could also occur secondary to
      microglial degeneration.

PMID- 16651882
TI  - The burden of radiation-induced central nervous system tumors: a single
      institution s experience.
AB  - Radiation-induced tumors of the central and peripheral nervous systems are
      becoming a noticeable subset of tumors seen at referral institutions. This paper
      outlines a single institution s experience with 22 examples of secondary
      meningiomas, gliomas, and sarcomas that developed in adults. These tumors are
      being increasingly encountered by physicians, but the greatest burden is on the
      patients themselves, who not only experience the life-altering effects of the
      original tumor and the subsequent delayed cognitive effects of radiotherapy, but
      later develop a second intracranial neoplasm. We detail a particularly poignant
      example of a 34-year-old man who developed a high-grade sarcoma with
      rhabdomyosarcomatous and osteogenic elements. Local control was difficult over
      the next year, and he eventually developed cerebrospinal fluid dissemination and
      succumbed. Although radiation-induced neoplasm remain relatively infrequent
      numerically, each case reminds us of the need for new, less toxic, and more
      targeted therapies for brain neoplasms.

PMID- 16651883
TI  - Endoplasmic reticulum stress and apoptosis signaling in human temporal lobe
      epilepsy.
AB  - Apoptosis signaling pathways are implicated in the pathogenesis of temporal lobe
      epilepsy (TLE), but the role of endoplasmic reticulum (ER) stress and ER
      localized apoptosis signaling components remains largely unexplored. Presently,
      we investigated ER stress and ER localization of proapoptotic Bcl-2 family
      members and initiator and effector caspases in resected hippocampus from patients
      with intractable TLE and compared findings with autopsy controls. Hippocampal
      immunoreactivity for KDEL (Lys-Asp-Glu-Leu), a motif in ER stress chaperones
      glucose-regulated proteins 78 and 94, and calnexin, was significantly higher in
      TLE hippocampus compared with controls. The ER-containing microsomal fraction in
      control brain contained Bid, Bim, and caspase 3, whereas Bad and caspases 6, 7,
      and 9 were very low or absent. In contrast, caspases 6, 7, and 9 were present
      within the microsomal fraction of TLE brain. Furthermore, cleaved caspases 7 and
      9 were detected in TLE samples but not controls, and KDEL-expressing neurons
      coexpressed cleaved caspase 9. Potentially adaptive changes were also detected,
      including lowered Bim levels in this fraction, and binding of caspase 7 to the X
      linked inhibitor of apoptosis protein. These data suggest seizures may induce ER
      stress and trigger proapoptotic signaling pathways in the ER that are
      counteracted by antiapoptotic signals in chronic human TLE.

PMID- 16651884
TI  - Purkinje cell vulnerability to mild and severe forebrain head trauma.
AB  - Pathophysiological changes in the cortex, thalamus, and hippocampus have been
      implicated as contributors to motor and cognitive deficits in a number of animal
      models of traumatic brain injury (TBI). Indirect cerebellar injury may contribute
      to TBI pathophysiology because impairment of motor function and coordination are
      common consequences of TBI, but are also domains associated with cerebellar
      function. However, there is a lack of direct evidence to support this claim.
      Hence, in this study, a dose-response relationship of the cerebellum's
      susceptibility was determined at four grades of fluid percussion injury (1.5,
      2.0, 2.5, and 3.0 atm) applied in the right lateral cerebral cortex of adult male
      Sprague-Dawley rats. Evidence suggests primary and secondary injury mechanisms
      resulting in selective cerebellar Purkinje neuron (PN) loss, whereas interneurons
      of the molecular layer were spared. The posterior region of the cerebellar vermis
      displayed significant PN loss (p = 0.001) at 1 day postinjury, whereas the gyrus
      of the horizontal fissure and gyrus of lobules III and IV exhibited delayed PN
      loss at higher levels of injury severity. Interestingly, neither terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) or cleaved
      caspase-3 colocalized with PNs at any time point or injury severity. Expression
      of calbindin-28k increased in regions of greatest PN loss, suggesting that the
      surviving PNs possess higher calcium-buffering capacities, which may account for
      their survival.

PMID- 16651885
TI  - Stereologic analysis of microvascular morphology in the elderly: Alzheimer
      disease pathology and cognitive status.
AB  - The presence of microvascular changes has been documented both in brain aging and
      Alzheimer disease (AD), although the relationship between the morphometry of
      brain capillaries and cognitive impairment is still unknown. We performed an
      analysis of capillary morphometric parameters and AD-related pathology in 19
      elderly individuals with variable degrees of cognitive decline. Cognitive status
      was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total
      capillary lengths and numbers as well as mean length-weighted diameter, total
      neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were
      estimated in entorhinal cortex and the CA1 field. Total capillary numbers and
      mean diameters explained almost 40% of the neuron number variability in both the
      CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and
      entorhinal cortex did not predict cognitive status. Mean capillary diameters in
      the CA1 and entorhinal cortex were significantly related to CDR scores,
      explaining 18.5% and 31.1% of the cognitive variability, respectively. This
      relationship persisted after controlling for NFT and neuron numbers in
      multivariate regression models. Consistent with the growing interest about
      microvascular pathology in brain aging, the present data indicate that changes in
      capillary morphometric parameters may represent independent predictors of AD
      related neuronal depletion and cognitive decline.

PMID- 16651886
TI  - Endogenous cell repair of chronic demyelination.
AB  - In multiple sclerosis lesions, remyelination typically fails with repeated or
      chronic demyelinating episodes and results in neurologic disability. Acute
      demyelination models in rodents typically exhibit robust spontaneous
      remyelination that prevents appropriate evaluation of strategies for improving
      conditions of insufficient remyelination. In the current study, we used a mouse
      model of chronic demyelination induced by continuous ingestion of 0.2% cuprizone
      for 12 weeks. This chronic process depleted the oligodendrocyte progenitor
      population and impaired oligodendrocyte regeneration. Remyelination remained
      limited after removal of cuprizone from the diet. Fibroblast growth factor 2
      (FGF2) expression was persistently increased in the corpus callosum of
      chronically demyelinated mice as compared with nonlesioned mice. We used FGF2
      mice to determine whether removal of endogenous FGF2 promoted remyelination of
      chronically demyelinated areas. Wild-type and FGF2 mice exhibited similar
      demyelination during chronic cuprizone treatment. Importantly, in contrast to
      wild-type mice, the FGF2 mice spontaneously remyelinated completely during the
      recovery period after chronic demyelination. Increased remyelination in FGF2 mice
      correlated with enhanced oligodendroglial regeneration. FGF2 genotype did not
      alter the density of oligodendrocyte progenitor cells or proliferating cells
      after chronic demyelination. These findings indicate that attenuating FGF2
      created a sufficiently permissive lesion environment for endogenous cells to
      effectively remyelinate viable axons even after chronic demyelination.

PMID- 16651887
TI  - Increased metabolic activity in nucleus basalis of Meynert neurons in elderly
      individuals with mild cognitive impairment as indicated by the size of the Golgi
      apparatus.
AB  - In this study, we examined the metabolic activity of nucleus basalis of Meynert
      (NBM) neurons in individuals clinically diagnosed with no cognitive impairment
      (NCI, n = 8), mild cognitive impairment (MCI, n = 9), and subjects with moderate
      Alzheimer disease (AD, n = 7). We used Golgi apparatus (GA) size as a measure of
      neuronal metabolic activity. Subjects with MCI showed increased NBM metabolic
      activity; they had significantly more neurons with larger GA size as compared
      with NCI and AD subjects. In contrast, more NBM neurons with extremely small GA
      sizes, indicating reduced metabolic activity, were seen in AD. When these cases
      were classified according to their AD pathology (Braak I-II, III-IV, or V-VI),
      Braak III-IV subjects showed significantly increased GA sizes, comparable with
      the increase in clinically diagnosed MCI, whereas in Braak V-VI, GA sizes were
      dramatically reduced. Of all MCI and NCI subjects with similar Braak III-IV
      pathology, the MCI subjects again had significantly larger GA sizes. The larger
      NBM neuronal GA size seen in MCI suggests increased metabolic activity,
      associated with both the clinical progression from NCI to MCI, and with the early
      stages of AD pathology.

PMID- 16651888
TI  - Neuronal-specific roles of the survival motor neuron protein: evidence from
      survival motor neuron expression patterns in the developing human central nervous
      system.
AB  - Despite recent data on the cellular function of the survival motor neuron (SMN)
      gene, the spinal muscular atrophy (SMA) disease gene, the role of the SMN protein
      in motor neurons and hence in the pathogenesis of SMA is still unclear. The
      spatial and temporal expression of SMN in neurons, particularly during
      development, could help in verifying the hypotheses on the SMN protein functions
      so far proposed. We have therefore investigated the expression and subcellular
      localization of the SMN protein in the human central nervous system (CNS) during
      ontogenesis with immunocytochemical, confocal immunofluorescence, and Western
      blot experiments using a panel of anti-SMN antibodies recognizing the full-length
      SMN protein. The experiments not only revealed the early SMN expression in all
      neurons, but also demonstrated the progressive shift in SMN subcellular
      localization from mainly nuclear to cytoplasmic and then to axons during CNS
      maturation. This finding was present in selected neuronal cell populations and it
      was particularly conspicuous in motor neurons. Our data support the idea of a
      specific role for SMN in axons, which becomes predominant in the ontogenetic
      period encompassing axonogenesis and axonal sprouting. In addition, the
      asymmetric SMN staining demonstrated in the germinative neuroepithelium suggests
      a possible role for SMN in neuronal migration and/or differentiation.

PMID- 16651889
TI  - Biochemical staging of synucleinopathy and amyloid deposition in dementia with
      Lewy bodies.
AB  - The primary feature of dementia with Lewy bodies (DLB) is the aggregation of
      alpha-synuclein into characteristic lesions: Lewy bodies (LBs) and Lewy neurites.
      However, in most of DLB cases, LBs are associated with neurofibrillary tangles
      and amyloid plaques (both Alzheimer disease [AD]-related lesions). We wanted to
      determine if this overlap of lesions is statistical, as a result of the late
      onset of both diseases, or results from a specific physiopathological synergy
      between synucleinopathy and either tauopathy or amyloid pathology. All patients
      with DLB from our prospective and multidisciplinary study were analyzed. These
      cases were compared with cases with pure AD and patients with Parkinson disease
      and controls. All cases were analyzed thoroughly at the neuropathologic and
      biochemical levels with a biochemical staging of aggregated alpha-synuclein, tau,
      and Abeta species. All sporadic cases of DLB were associated with abundant
      deposits of Abeta x-42 that were similar in quality and quantity to those of AD.
      Amyloid precursor protein (APP) dysfunction is a risk factor for AD as
      demonstrated by pathogenic mutations and Abeta accumulation. The constant and
      abundant Abeta x-42 deposition in sporadic DLB suggests that synucleinopathy is
      also promoted by APP dysfunction. Therefore, we conclude that APP is a
      therapeutic target for both AD and DLB.

PMID- 16651890
TI  - Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian
      frontotemporal lobar degeneration family.
AB  - The most common histologic feature in patients with frontotemporal lobar
      degeneration (FTLD) is intracellular brain inclusions of yet uncharacterized
      proteins that react with antiubiquitin (Ub) antibodies, but not with tau or
      synuclein (FTLD-U). We identified a four-generation Belgian FTLD family in which
      8 patients had dominantly inherited FTLD. In one patient, we showed
      frontotemporal atrophy with filamentous Ub-positive intracellular inclusions in
      absence of tau pathology or any alterations in the levels of soluble tau. We
      characterized the cellular and subcellular localization and morphology of the
      inclusions. Ub-positive inclusions predominantly occurred within neurons (>97%),
      but were also observed within oligodendroglia (approximately 2%) and microglia
      (<1%), but not within astroglia. Regarding the subcellular localization, the
      intranuclear inclusions (INI) were up to approximately four-fold more frequent
      than the cytoplasmic inclusions, although the latter were more specific to
      neurons. The INIs frequently appeared spindle-shaped and 3-dimensional confocal
      reconstructions identified flattened, leaf-like structures. Ultrastructurally,
      straight 10- to 18-nm-diameter filaments constituted the spindle-shaped
      inclusions that occurred in close proximity to the nuclear membrane. Staining for
      HSP40, p62, and valosin/p97 was observed in only a minority of the inclusions.
      Whereas the precise nature of the protein remains elusive, characterization of
      such familial FTLD-U patients would be helpful in identifying a common
      denominator in the pathogenesis of familial and the more prevalent sporadic FTLD
      U.

PMID- 16651892
TI  - Pitfalls of the morphologic approach.

PMID- 16651893
TI  - Excellence is nonnegotiable... and the right thing to do.

PMID- 16651895
TI  - Nurses "gamble" on nurses to provide staffing solution.

PMID- 16651896
TI  - What you don't know about the FMLA can hurt you.

PMID- 16651897
TI  - The good news about managed care organizations.

PMID- 16651898
TI  - See the positive side of sentinel events.

PMID- 16651899
TI  - Vascular safety: it's all about PICCs.

PMID- 16651900
TI  - Nurse collegiality: fact or fiction?

PMID- 16651901
TI  - Research to practice: don't get lost in translation.

PMID- 16651902
TI  - Nursing in the dark: leadership support for night staff.

PMID- 16651903
TI  - How to open new nursing units: a blueprint for success.

PMID- 16651905
TI  - Enjoy "smarter" patient monitoring.

PMID- 16651906
TI  - Challenge: new educational levels.

PMID- 16651907
TI  - Child abuse fatalities: are we missing opportunities for intervention?
AB  - OBJECTIVE: Child abuse is a leading cause of childhood morbidity and mortality
      and often goes unrecognized until severe injury or death has occurred. This study
      describes a cohort of fatally abused children and explores contacts with the
      health care community, which may represent missed opportunities for recognition
      and intervention. METHODS: Homicide deaths in children younger than 10 years were
      identified through medical examiners' records from a 4-county area from 1999 to
      2002. Medical records from the 3 area children's hospitals were searched for
      health care visits by the subjects before death. Subject demographics, cause of
      death, injury patterns, person supervising the child, and recent contacts with
      the health care community were collected from medical examiner and hospital
      records. RESULTS: Forty-four cases were identified, with 37 subjects (84%)
      younger than 4 years. Further analysis focused on these 37 younger subjects.
      Causes of death were blunt head injury, 57%; blunt torso injury, 13%; gunshot
      wound, 11%; fire, 8%; drowning, 8%; and poisoning, 3%. Fractures were noted in 9
      children (24%), 7 children with fractures at different stages of healing. Eleven
      children (30%) had documented health care visits for reasons other than routine
      well-child care in the year before their death, including 7 children (19%) with
      such visits within a month before their death. CONCLUSIONS: Child homicides in
      this cohort occurred primarily in younger children, among whom the most common
      cause of death was blunt trauma. Almost 20% of this subgroup had documented
      contact with the health care community for reasons other than routine care within
      a month before their death. Some of these presentations are suspicious for
      undiagnosed abusive injuries, which, if properly identified, could serve as
      opportunities for life-saving intervention.

PMID- 16651908
TI  - Protocols for pediatric poisonings from nontoxic substances: are they valid?
AB  - OBJECTIVES: Most pediatric poisonings have favorable outcomes and are managed in
      the home by poison control centers utilizing protocols that deem products or
      substances as nontoxic. We sought to evaluate the validity of protocols for
      nontoxics. METHODS: This is retrospective study in which poison control center
      case records within a statewide poison control center system during calendar year
      2001 were searched for products or substances involved in a pediatric poisoning
      ingestion and identified in the poison control center nontoxic substance or
      product list. This was coupled with systematic literature search to ascertain if
      any significant medical outcomes were associated with ingestion of a nontoxic
      substance or product. RESULTS: During the 1-year study period, 20,900 pediatric
      ingestions involving 46 different nontoxic substances or products were analyzed
      for significant outcomes. Only 6 cases (0.03%) had a potentially serious clinical
      effect requiring emergency hospital management. The literature search revealed
      2326 ingestion cases of nontoxic products from 635,000 citations in 50 different
      databases. Of these, 28 cases (1.2%) described an effect, although none was
      described as significant. CONCLUSIONS: Poisoning protocols for pediatric
      ingestions of substances or products we deemed as nontoxic were rarely associated
      with significant outcomes. However, non-dose-related potentially life-threatening
      effects are possible. Therefore, use of nontoxic protocols by other health care
      practitioners for telephone triage or by the public directly requires further
      study to be valid. Our study suggests that the term nontoxic is misleading and
      recommends that it be replaced with "minimally toxic" as a more appropriate term
      for identifying the lowest level of risk of toxicity from a substance or product.

PMID- 16651909
TI  - Cardiac troponin I as a predictor of mortality for pediatric submersion injuries
      requiring out-of-hospital cardiopulmonary resuscitation.
AB  - BACKGROUND: It is difficult to predict ultimate survivors to hospital discharge
      in children who are successfully resuscitated after a cardiorespiratory arrest
      associated with a submersion injury. Serum measurements of organ injury or
      dysfunction may serve as a surrogate marker of the degree of hypoxic injury. We
      designed a prospective study whose purpose was to assess the predictive value for
      outcome of serum cardiac troponin I measurements after submersion injury and
      cardiorespiratory arrest. METHODS: This is a prospective, observational study of
      children admitted to a postintensive care unit after experiencing an out-of
      hospital cardiorespiratory arrest associated with a submersion event. Cardiac
      troponin I measurements were examined upon admission to the postoperative
      intensive care unit after successful emergency department resuscitation. RESULTS:
      Nine patients were admitted, and 2 patients (22%) survived to hospital discharge.
      The area under the receiver operating characteristic curve is 0.786 (95%
      confidence interval, 0.481-1.0). This suggests that cardiac troponin I has a
      moderate degree of discriminatory power in selecting children who did not survive
      to hospital discharge.

PMID- 16651910
TI  - Pediatric laryngoscope blade size selection using facial landmarks.
AB  - OBJECTIVES: The study evaluates whether facial landmarks can be used to estimate
      an appropriate laryngoscope blade length for oral endotracheal intubation in
      children. We tested the hypothesis that the laryngoscope blade measuring 10 mm or
      less distal or proximal to the angle of the mandible (when the flat portion of
      the blade follows the facial contour from the upper incisor teeth to the angle of
      the mandible) will demonstrate greater success and ease of oral tracheal
      intubation. METHODS: We performed an observational study that prospectively
      evaluated a convenience sample of children 8 years old or younger and who were
      undergoing direct laryngoscopy for oral endotracheal intubation in the operating
      room, outpatient surgery center, emergency department, or pediatric intensive
      care unit of a tertiary referral medical center. Ease and success of oral
      tracheal intubation were compared with distance measurements from the angle of
      the mandible to the tip of the laryngoscope blade. RESULTS: Blade lengths
      considered too short (blade lengths >10 mm proximal to the angle of the mandible)
      were more likely to be associated with more than 1 attempt at intubation. Only
      57.1% (12/21; 95% confidence interval [CI], 36.5-75.5) of the intubations using
      the shorter blade were performed on the first attempt as compared with 89.7%
      (26/29; 95% CI, 73.6-96.4) of the intubations using the recommended length or
      85.7% (6/7; 95% CI, 48.7-97.4) of the intubations using blades extending longer
      than 10 mm past the angle of the mandible. CONCLUSIONS: The distance from the
      upper incisor teeth to the angle of the jaw seems to be an excellent clinical
      landmark for laryngoscope blade length selection for pediatric intubations. When
      the blade (excluding the handle insertion block) is placed at the upper midline
      incisor teeth and the tip is located within 1 cm proximal or distal to the angle
      of the mandible, oral tracheal intubations are more consistently accomplished on
      the first attempt. Our observations suggest that facial landmarks can be used to
      estimate an appropriate laryngoscope blade length for oral endotracheal
      intubation in children.

PMID- 16651911
TI  - Parental presence during invasive procedures and resuscitation: attitudes of
      health care professionals in Turkey.
AB  - OBJECTIVES: An agreement among physician, nurse, and family on the issue and a
      solution developed by all will improve the quality of work. The aims of this
      study were to determine health care professionals' (physicians and nurses)
      attitude toward parental presence during invasive procedures and toward parental
      participation in this decision and to investigate the difference between the
      approach of physicians and nurses. METHODS: This study was performed on the
      physicians and nurses of the Medical Faculty of the Department of Pediatrics of
      Ege University between December 2003 and March 2004. The questionnaire delivered
      was completed by 49 (94%) of 52 nurses and 51 (89%) of 57 physicians. RESULTS:
      Parental presence during blood sampling, simple wound repair/suture, lumbar
      puncture, and bone marrow aspiration/biopsy was approved by 72.5%, 27.5%, 66.7%,
      and 82.4% of the physicians and 53.1%, 57.1%, 81.6%, and 85.7% of the nurses,
      respectively. None of the health care professionals preferred parents to attend
      during any kind of resuscitation. Attitudes of the nurses and physicians were
      found to be similar between the 2 groups except for simple wound repair. Major
      determinants of the decision about the agreement for parental presence were
      procedural invasiveness for physicians (reported by 82.5%) and level of sedation
      for nurses (reported by 75.5%). The mean ages of both groups of health care
      professionals who did not approve parental presence during invasive procedures
      were lower than that of the ones who approved for all procedures. CONCLUSION: The
      physicians and nurses in the study population tended to prefer parents not to be
      present during procedures as the level of invasiveness increased. An agreement
      between the attitudes of physicians and nurses toward parental presence during
      invasive procedures is essential for improving quality of service, especially in
      the dynamic environment of the emergency department.

PMID- 16651912
TI  - Randomized comparison of pain perception during radial head subluxation reduction
      using supination-flexion or forced pronation.
AB  - OBJECTIVE: To determine if a difference exists in perceived pain between the
      forced pronation and supination-flexion methods of radial head subluxation (RHS)
      reduction. DESIGN AND METHODS: We developed a prospective randomized trial of
      children aged 6 months to 7 years who presented to the emergency department (ED)
      at Miami Children's Hospital with an immobile arm and physical findings
      suggestive of RHS. Children were randomized into 2 groups for RHS reduction:
      forced pronation and supination-flexion. Parents, physicians, and nurses were
      given a standard visual analog pain scale for pain assessment before, during, and
      at 1 minute after successful reduction. RESULTS: Seventy-five children presented
      to the ED with RHS; 3 children were excluded from the study because of
      nonadherence to the protocol and another 9 were excluded because of unsuccessful
      reduction during the first attempt. Of the remaining children, 32 children
      underwent forced pronation and 31 underwent supination-flexion. Physicians did
      not find a significant difference in gain scores between their perceptions of the
      premeasure and postmeasure of pain between those patients receiving supination
      flexion and those receiving forced pronation. For nurses (P < 0.031) and parents
      (P < 0.043), there were statistically significant differences in gain scores.
      Nurses and parents perceived forced pronation as being less painful. The mean
      difference for parents was 1.7 cm, which exceeded the value of 1.3 cm identified
      as clinically significant. CONCLUSIONS: Forced pronation is perceived as less
      painful than the supination-flexion method by parents of children treated for RHS
      in our ED.

PMID- 16651913
TI  - Pediatric nerve agent poisoning: medical and operational considerations for
      emergency medical services in a large American city.
AB  - Most published recommendations for treatment of pediatric nerve agent poisoning
      are based on standard resuscitation doses for these agents. However, certain
      medical and operational concerns suggest that an alternative approach may be
      warranted for treatment of children by emergency medical personnel after mass
      chemical events. (1) There is evidence both that suprapharmacological doses may
      be warranted and that side effects from antidote overdosage can be tolerated. (2)
      There is concern that many emergency medical personnel will have difficulty
      determining both the age of the child and the severity of the symptoms.
      Therefore, the Regional Emergency Medical Advisory Committee of New York City and
      the Fire Department, City of New York, Bureau of Emergency Medical Services, in
      collaboration with the Center for Pediatric Emergency Medicine of the New York
      University School of Medicine and the Bellevue Hospital Center, have developed a
      pediatric nerve agent antidote dosing schedule that addresses these
      considerations. These doses are comparable to those being administered to adults
      with severe symptoms and within limits deemed tolerable after inadvertent nerve
      agent overdose in children. We conclude that the above approach is likely a safe
      and effective alternative to weight-based dosing of children, which will be
      nearly impossible to attain under field conditions.

PMID- 16651914
TI  - Apparent life-threatening event or child abuse?
AB  - Children with apparent life-threatening events (ALTEs) often pose a diagnostic
      and management dilemma in a pediatric emergency department. Although the term
      ALTE is nonspecific and symptoms are vague, it may have alarming connotations and
      may signal serious life threatening conditions. It may be a subtle presentation
      of child abuse. We report an infant who was presented with an ALTE and
      subsequently determined to have subdural hematoma caused by nonaccidental injury.

PMID- 16651915
TI  - Recurrent episodes of intractable laryngospasm during dissociative sedation with
      intramuscular ketamine.
AB  - We report 2 cases of dissociative sedation with intramuscular ketamine with
      recurrent episodes of laryngospasm that we were unable to ventilate with bag-mask
      ventilation, in 1 case leading to endotracheal intubation to protect the airway.
      Supplemental oxygen was given throughout the sedations, and ventilatory status
      was noninvasively monitored on a continuous basis, providing detailed and
      objective documentation of the patients' clinical status throughout the
      sedations. We were, therefore, able to rapidly assess and confirm apnea,
      laryngospasm, and airway dysfunction.

PMID- 16651916
TI  - Streptococcal pyomyositis of the psoas: case reports and review.
AB  - We present two unusual cases of pyomyositis of the psoas muscle caused by Group A
      beta-hemolytic streptococcus (GABHS) in children presenting with fever, emesis
      and leg pain. Pyomyositis secondary to GABHS is rare in children and cases
      involving the psoas muscle have not been previously reported. In our discussion,
      we review the epidemiology, presentation, diagnosis and treatment of GABHS psoas
      myositis in comparison with staphylococcal pyomyositis. Prompt recognition of the
      signs and symptoms of GABHS psoas pyomyositis is essential for treatment of this
      life-threatening infection.

PMID- 16651917
TI  - Chlorine-related inhalation injury from a swimming pool disinfectant in a 9-year
      old girl.
AB  - Chlorine is a potential respiratory hazard in both occupational and household
      settings. The clinical sequelae of inhalation are variable in severity and
      timing, and subacute presentation is a concern. We report the case of a 9-year
      old girl who developed dyspnea, hypoxemia, and pneumonitis approximately 12 hours
      after exposure to chlorine released from aerosolized swimming pool purification
      tablets. Her course was characterized by improvement with supplemental oxygen and
      bronchodilator therapy. Follow-up pulmonary testing at 4 months after the episode
      revealed the presence of mild obstructive reactivity of the airways, but she was
      able to perform normal activities without requiring medications. We discuss the
      pathophysiology, symptoms, therapy, and long-term follow-up of chlorine
      inhalation injuries.

PMID- 16651918
TI  - Intrathecal baclofen overdose and withdrawal.
AB  - Intrathecal baclofen (ITB) therapy is being used increasingly to treat medically
      intractable spasticity in children with cerebral palsy and spinal cord injuries.
      Baclofen overdose and withdrawal are potentially life-threatening complications
      of pump and spinal catheter system malfunction. We report a case of a 12-year-old
      boy, on long-term ITB therapy, who presents to our emergency department with an
      overdose of ITB, which is followed by withdrawal symptoms. The patient initially
      presented obtunded and in respiratory arrest. His symptoms of respiratory arrest,
      obtundation, fixed pupils, and hypotension mimicked other diagnoses, such as head
      trauma. The history obtained from the family about the pump reservoir being
      refilled just before the onset of symptoms led to the diagnosis. During
      hospitalization, as the patient recovered from the overdose, he began to
      experience symptoms of baclofen withdrawal, including hypertension, hyperthermia,
      and hallucinations. The pump was found to be disconnected and was revised. The
      patient was discharged home without permanent sequelae. With increased use of
      ITB, emergency medicine physicians must be aware of the mechanics of these pumps
      and the management of baclofen toxicity and withdrawal.

PMID- 16651919
TI  - Case report: esophageal foreign body mistaken for impacted button battery.
AB  - Foreign body ingestion is a common complaint in the pediatric emergency
      department. Here, we report an interesting case of a coin ingestion in which the
      radiographic findings were alarming and inconsistent with the history provided by
      our patient. A brief review of the diagnosis and management of gastrointestinal
      foreign bodies is presented, with particular focus on ingested coins and button
      batteries.

PMID- 16651920
TI  - Known asthmatic: right-side wheezing.

PMID- 16651921
TI  - Management of primary herpetic gingivostomatitis in young children.
AB  - OBJECTIVE: To review the treatment of primary herpetic gingivostomatitis at a
      children's hospital. METHODS: A review of charts from 1999 to 2003. RESULTS:
      Forty-eight cases were identified. They ranged in age from 8 months to 12 years,
      with a median age of 2 years 7 months. All children were treated with fluids and
      analgesics; 11 children were treated with fluids and analgesics exclusively.
      Thirty-five children were treated with a mixture of Maalox and diphenhydramine, 8
      with acyclovir, and 7 with viscous lidocaine; 11 children were treated with 2 or
      more of these regimens. Both the Maalox and diphenhydramine mixture and the
      viscous lidocaine were administered as swish and swallow, swish and spit, or by
      application with a swab as frequently as every hour or as infrequently as every 8
      hours. CONCLUSIONS: Topical therapy with Maalox and diphenhydramine or viscous
      lidocaine was administered to 73% and 15% of the patients, respectively, whereas
      acyclovir was administered to only 17%. Dosing and administration of topical
      agents in the treatment of primary herpetic gingivostomatitis in preschoolers
      were problematic. Acyclovir was not being used as often as it could have been.

PMID- 16651922
TI  - Emergency department perspective on methicillin-resistant Staphylococcus aureus.

PMID- 16651924
TI  - ECGs in the ED.

PMID- 16651925
TI  - Child and adolescent psychiatric emergencies: the need for a clear research
      agenda.

PMID- 16651926
TI  - Acute otitis media-to treat or not to treat?

PMID- 16651928
TI  - Hypersensitivity reaction to hyaluronic acid with negative skin testing.

PMID- 16651929
TI  - Surgical management of the windblown hand in the adult.

PMID- 16651930
TI  - Total peroneal artery occlusion during fibula free flap harvesting: salvage using
      the venous flow-through principle.

PMID- 16651931
TI  - Feminizing genitoplasty for treatment of XX male with masculine genitalia.

PMID- 16651932
TI  - Z-plasty of dorsal and plantar flaps for hallux varus with preaxial polydactyly
      of the foot.

PMID- 16651933
TI  - Thumb trapeziometacarpal arthritis: treatment with ligament reconstruction tendon
      interposition arthroplasty.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the pathomechanical and biochemical basis for thumb
      trapeziometacarpal joint degeneration. 2. Diagnose and grade trapeziometacarpal
      joint disease based on presentation, physical examination (including provocative
      testing), and radiographic evidence. 3. Understand the principles of ligament
      reconstruction and tendon arthroplasty procedures. 4. Describe the surgical
      technique for ligament reconstruction tendon interposition arthroplasty and its
      variants. BACKGROUND: Osteoarthritis of the trapeziometacarpal joint is the
      second most common site of degenerative joint disease in the hand, and mostly
      affects postmenopausal women. Degenerative arthritis of the thumb
      trapeziometacarpal joint is associated with a lack of bony constraints and laxity
      of the supporting ligaments, particularly the anterior oblique ("beak") ligament,
      which is consistently implicated in disease progression. Resultant increases in
      joint stress loads leads eventually to metacarpal and trapezial articular
      destruction, thumb instability, and pain. METHODS: In this article, the authors
      review the diagnosis and treatment modalities available to the surgeon in the
      treatment of patients with trapeziometacarpal osteoarthritis. The technique of
      ligament reconstruction tendon interposition arthroplasty is discussed in detail.
      RESULTS: Ligament reconstruction tendon interposition arthroplasty procedures
      center on three common principles: (1) excision of the diseased trapezium; (2)
      reconstruction of the beak ligament; and (3) interposition of a tissue substance
      to maintain metacarpal position. CONCLUSIONS: Both conservative and surgical
      management can be effective in the treatment of trapeziometacarpal arthritis,
      when properly selected. The success of ligament reconstruction tendon
      interposition arthroplasty in treating trapeziometacarpal arthritis has withstood
      the test of time.

PMID- 16651934
TI  - Satisfaction with prophylactic mastectomy and breast reconstruction in
      genetically predisposed women.
AB  - BACKGROUND: Prophylactic mastectomy with breast reconstruction is a risk-reducing
      strategy for women at increased risk of breast cancer. It remains a very radical
      intervention, and long-term data on satisfaction are insufficiently available. In
      the present follow-up study, the authors assess satisfaction with prophylactic
      mastectomy and breast reconstruction and its impact on sexual relationships.
      METHODS: The authors conducted a retrospective study using a short self-report
      questionnaire administered to 114 genetically predisposed women who underwent
      prophylactic mastectomy and breast reconstruction mainly by subpectorally
      implanted silicone prostheses performed at one institution. RESULTS: The median
      follow-up time between prophylactic mastectomy/breast reconstruction and
      completion of the questionnaire was 3 years. Sixty percent of all participants
      were satisfied with the result of prophylactic mastectomy/breast reconstruction.
      Satisfaction was significantly and negatively correlated with perceived lack of
      information, experienced complications, ongoing complaints, whether or not the
      reconstructed breasts feel "like your own," and not choosing this type of breast
      reconstruction again. Adverse effects in the patient's sexual relationship were
      strongly correlated with perceived lack of information, discrepant expectations,
      ongoing complaints and limitations, whether or not the reconstructed breasts feel
      "like your own," altered feelings of femininity, partner's negative perception on
      femininity and sexuality, and not choosing this type of breast reconstruction
      again. CONCLUSIONS: A majority of women would choose the procedure again, but
      adverse effects and untoward changes in the perception of the sexual relationship
      need to be addressed in the counselling of women at high risk, to optimize an
      informed choice and enable adequate adjustment postoperatively.

PMID- 16651936
TI  - Respecting the aesthetic unit in autologous breast reconstruction improves the
      outcome.
AB  - BACKGROUND: In postmastectomy breast reconstruction, a patchwork-like appearance
      and a double-bubble phenomenon may result from scar contracture and the possible
      destruction of the normal inframammary fold during mastectomy. Restoring an age
      related breast ptosis can be difficult, and often contralateral breast surgery
      has to be performed to achieve symmetry. The purpose of this article is to
      present a technique that respects the aesthetic unit in autologous
      reconstruction, improves the outcome, and minimizes secondary surgery. METHODS:
      The area between the resected mastectomy scar and the marked inframammary fold is
      deepithelialized. The inferior skin margin of the flap is sutured to the lower
      line of the deepithelialized area, which corresponds to the inframammary fold of
      the contralateral side. The degree of ptosis can be adjusted by insetting greater
      or lesser amounts of skin. From December of 2000 to June of 2004, 12 patients
      underwent secondary breast reconstruction using this technique. The patients'
      ages ranged from 39 to 63 years (median, 51 years). Three patients had reduction
      mammaplasty of the contralateral breast. RESULTS: Mean patient follow-up was 14.7
      months (range, 4 to 45 months). There were no free flap failures. Cosmetic
      evaluation of the reconstructed breasts by two independent plastic surgeons
      showed good results with regard to symmetry in 10 patients and fair results in
      two patients. Concerning visibility of the inferior scar, 11 patients had a good
      result and one patient had a fair result. All patients had a good result in terms
      of age-appropriate ptosis. CONCLUSIONS: The authors' technique facilitates the
      formation of an age-appropriate ptosis. Altogether, the aesthetic unit of the
      breast is restored.

PMID- 16651938
TI  - Nipple-areola complex sensitivity after primary breast augmentation: a comparison
      of periareolar and inframammary incision approaches.
AB  - BACKGROUND: The body of literature documenting normative breast sensation and
      postoperative changes in sensation after reduction mammaplasty has grown
      considerably over the last several years. Despite this, only two studies have
      ever been published on the subject of postaugmentation mammaplasty sensory
      outcomes. The purpose of this study was to precisely measure sensory thresholds
      at the nipple-areola complex in women who have undergone augmentation mammaplasty
      by either the inframammary or periareolar approach. METHODS: Twenty women
      underwent primary augmentation mammaplasty by either the periareolar or
      inframammary approach at an average follow-up of 1.12 years. Sensory testing was
      performed using the Pressure-Specified Sensory Device by comparing moving and
      static sensory thresholds at the upper and lower areola and nipple. Nine women
      served as size-matched, nonoperated controls in the study. RESULTS: Primary
      augmentation mammaplasty was found to have a statistically significant negative
      effect on sensory outcomes when nonoperated controls were compared with women who
      had undergone augmentation mammaplasty via either the periareolar or inframammary
      approach. No differences in sensory outcomes were found between the two
      approaches used. Implant volume was found to be highly predictive of sensory
      outcomes, with an inverse relationship between implant size and the degree of
      sensitivity within the nipple-areola complex. CONCLUSIONS: Plastic surgeons
      should feel comfortable counseling patients that augmentation mammaplasty by
      either the inframammary or periareolar approach results in no discernible
      differences in sensory outcomes. Furthermore, women who choose very large
      implants relative to their breast skin envelopes should be warned about potential
      adverse sensory sequelae within the nipple-areola complex.

PMID- 16651939
TI  - The role of the lateral thoracodorsal fasciocutaneous flap in immediate
      conservative breast surgery reconstruction.
AB  - BACKGROUND: Although the lateral thoracodorsal fasciocutaneous flap is a well
      studied procedure for late breast reconstruction following radical surgery, there
      are few previous reports regarding its indication, flap design, and clinical
      outcome following conservative breast surgery. METHODS: Thirty-four patients
      underwent immediate unilateral lateral thoracodorsal fasciocutaneous flap breast
      reconstructions. Mean time of follow-up was 23 months. The lateral thoracodorsal
      fasciocutaneous flap was indicated to reconstruct moderate lateral breast defects
      where there was not enough breast tissue to perform the reconstruction. Flap and
      donor-site complications were evaluated. Information on aesthetic results and
      patient satisfaction was collected. RESULTS: All tumors were located in lateral
      breast regions, and 64.7 percent measured 2 cm or less (T1). Flap complications
      occurred in four patients (11.8 percent), with partial flap necrosis in three
      (8.8 percent). Donor-site complications occurred in eight (23.5 percent), with
      seroma in five (14.7 percent) and wound dehiscence in three (8.8 percent). The
      cosmetic result was considered to be good or very good in 88.2 percent, and the
      majority of patients were either very satisfied or satisfied. Surgical
      intervention was necessary in two cases of wound dehiscence. Serial dorsal
      puncture in cases of seroma were performed with satisfactory results.
      CONCLUSIONS: The lateral thoracodorsal fasciocutaneous flap is a simple and
      reliable technique for conservative breast surgery reconstruction. Success
      depends on patient selection, coordinated planning with the oncologic surgeon,
      and careful intraoperative management.

PMID- 16651940
TI  - DIEP and pedicled TRAM flaps: a comparison of outcomes.
AB  - BACKGROUND: Studies comparing similar and sizable numbers of deep inferior
      epigastric perforator (DIEP) and pedicled transverse rectus abdominis
      musculocutaneous (TRAM) flap reconstructions are lacking. The authors hoped to
      determine whether the DIEP flap has advantages over the pedicled TRAM flap for
      breast reconstruction. METHODS: The authors retrospectively reviewed the records
      of women undergoing breast reconstruction over a 9-year period at a single
      institution. Patients were grouped by type of reconstruction: DIEP or pedicled
      TRAM. Only patients with at least 3 months of postoperative follow-up were
      studied. RESULTS: A total of 190 women underwent unilateral breast
      reconstructions (96 DIEP and 94 pedicled TRAM flaps). The patient groups were
      similar in terms of age, body mass index, preoperative chest wall irradiation and
      abdominal operations, and cancer stage. The median hospital stay for the DIEP
      group was shorter than that for the pedicled TRAM group (4 versus 5 days, p <
      .001). Operative time for the DIEP group (5:53 hours) was longer than that for
      the pedicled TRAM group (4:46 hours, p < .001). The fat necrosis rates for the
      pedicled TRAM group were higher (58.5 percent) than those for the DIEP group
      (17.7 percent, p < .001). Abdominal wall hernias occurred more frequently in
      pedicled TRAM (16.0 percent) than DIEP patients (1.0 percent, p < .001).
      Abdominal wall bulge rates were similar for both groups (DIEP 9.4 percent versus
      pedicled TRAM 14.9 percent). CONCLUSIONS: DIEP flap reconstruction can be
      performed with lower morbidity rates and shorter hospital stays than pedicled
      TRAM reconstruction. Specifically, fat necrosis and abdominal wall hernias are
      less common in DIEP patients than in pedicled TRAM patients, while flap failure
      and abdominal wall bulging rates are similar in the two patient groups. These
      data support the DIEP flap as the preferred option over the pedicled TRAM flap
      for autologous breast reconstruction in postmastectomy patients.

PMID- 16651942
TI  - A simple barrier drape for breast implant placement.

PMID- 16651943
TI  - Nonresective shrinkage of the septum and fat compartments of the upper and lower
      eyelids: a comparative study with carbon dioxide laser and Colorado needle.
AB  - BACKGROUND: The purpose of this article is to describe an alternative
      nonresective treatment of the fat-septum component of the eyelids during
      blepharoplasty, using shrinkage desiccation with two low-energy modalities: a
      carbon dioxide laser and a low-range grid of electrocautery with a Colorado
      microdissection needle. METHODS: Thirty-six patients underwent a four-lid
      blepharoplasty. During surgery, after exposure (not opening) of the septum and
      assessment of the amount of bulging by gentle globe compression, a grid spray of
      electrocautery (right eye) and carbon dioxide laser (left eye) was applied over
      the entire septum until shrinkage and correction of the bulging was achieved.
      Preoperative, postoperative day 15, and 1-year follow-up photographs were
      evaluated using an objective grading system by blinded surgeons. For statistical
      analysis, the Wilcoxon matched-pairs signed-ranks test was used, with p < 0.05
      indicating statistical significance. RESULTS: All the patients completed the 15
      day evaluation, but only 32 completed the 1-year follow-up. No major eye or
      eyelids complications were observed. There were no statistical differences in
      surgical time and postoperative pain on either side. In this study, laser fat
      septum shrinkage achieved substandard results compared with electrocautery when
      analyzed as a continuous variable, but it did not influence the categorical
      Strasser scale final result in the short- and long-term follow-up. CONCLUSIONS:
      The method described is simple and safe, and provides a subtle but long-lasting,
      adequate result. No statistical clinical differences were observed between the
      electrocautery and laser fat-septum shrinkage techniques.

PMID- 16651945
TI  - Lifestyle outcomes, satisfaction, and attitudes of patients after liposuction: a
      Dallas experience.
AB  - BACKGROUND: Liposuction is the most common cosmetic operation performed. To the
      authors' knowledge, no report has examined patients' attitudes and postoperative
      opinions, lifestyle changes, weight gain changes, and satisfaction with their
      liposuction procedure in general and by specific site. The authors report on data
      from a survey provided to patients by two plastic surgeons at the University of
      Texas Southwestern Medical Center at Dallas. METHODS: Six hundred questionnaires
      were mailed to all patients who had liposuction surgery performed between 1999
      and 2003. There were 108 undeliverable surveys; 209 completed surveys were
      returned (34.8 percent of 600 and 42.5 percent of 492 surveys). Data were
      analyzed using the chi-square test. A p value of less than 0.05 was considered
      significant. RESULTS: The majority of patients (80 percent) were satisfied with
      their results. Fifty-three percent thought that their appearance was either
      "excellent" or "very good." With regard to satisfaction by site treated, 60
      percent or more of the responders were "very satisfied" or "satisfied" with their
      results. Weight gain was reported in 43 percent of the responders, with 56
      percent of them gaining between 5 and 10 pounds 6 months after their surgery. Fat
      return was reported in 65 percent of the responders. The abdomen was the most
      common location for fat return. As a group, 79.7 percent would have the procedure
      again and 86 percent would recommend the procedure to family or friends.
      Approximately 75 percent of responders described their postoperative discomfort
      as mild to moderate, with 60 percent indicating that their discomfort lasted less
      than 7 days (39.8 percent indicated their pain lasted longer than 7 days); 83
      percent indicated that they only needed to use narcotics for 7 days of less. When
      responders were divided into groups, the great majority of patients were
      satisfied with the surgery and their results. CONCLUSIONS: Despite postoperative
      pain, fat return, and weight gain, patients were willing to have the procedure
      again and recommend it to others. Those patients who were unsatisfied and were
      less likely to refer patients were those who had the lowest opinion of their
      appearance.

PMID- 16651946
TI  - Securing nasal tip rotation through suspension suture technique.
AB  - BACKGROUND: Multiple techniques have been described to produce tip rotation in
      rhinoplasty, including the use of sutures, a technique popularized by several
      authors and shown to be predictable, controllable, and nondestructive. The
      authors describe a simple procedure for nasal tip rotation with a suture
      suspension technique through a closed method that allows the nasal tip to be
      rotated while maintaining its appropriate position. METHODS: In each case, after
      the authors performed standard rhinoplasty techniques, the osteocartilaginous
      junction was used as an anchor for their suture suspension technique. This
      technique requires the use of a guide that positions the sutures across the
      medial side of both domes of the alar cartilages and osteocartilaginous junction.
      RESULTS: Between September of 2002 and September of 2004, this technique was used
      in 30 patients with nasal tip ptosis who requested improvement of this condition.
      There were 21 primary rhinoplasty and nine secondary rhinoplasty procedures. The
      results were satisfactory in all of the patients, but four patients had minimal
      asymmetries of the tip. In the follow-up of these patients, the projection of the
      nasal tip was maintained long term. CONCLUSION: With this suspension suture
      technique, the authors were able to maintain the optimal position of the nasal
      tip, using the osteocartilaginous junction as a pillar to provide long-term
      stability of the nasal tip.

PMID- 16651948
TI  - Use of botulinum toxin type A to prevent widening of facial scars.
AB  - BACKGROUND: Wounds of the face, especially those lying perpendicular to the lines
      of Langer, are known to heal poorly with conspicuous scarring. Different methods
      have been tried to tackle this problem, including corticosteroid injections,
      irradiation, ultrasound, silicone applications, and many others. However, as
      expected, their effects were far from satisfactory, because they do nothing to
      alleviate the underlying pathologic process, which is the distracting effect of
      muscle pull on immature collagen. METHODS: In 40 patients with ugly scars of the
      face, botulinum toxin was used to induce temporary paralysis of the muscles
      during revision surgery, thus minimizing tension on healing wound edges until the
      collagen could mature. RESULTS: Using both objective and subjective assessment
      scales, 90 percent of patients ended up with an improved outcome. This new
      technique has been proven effective in primates and in this study was shown to be
      as effective in humans, yielding results superior to those of any other treatment
      modality. CONCLUSION: In view of the results of this study, it is considered
      worthwhile to offer patients with ugly scars of the face botulinum toxin
      injections simultaneous with revision surgery.

PMID- 16651950
TI  - Evaluation of a novel technique for wound closure using a barbed suture.
AB  - BACKGROUND: Suture knots present several disadvantages in wound closure, because
      they are tedious to tie and place ischemic demands on tissue. Bulky knots may be
      a nidus for infection, and they may extrude through skin weeks after surgery.
      Needle manipulations during knot-tying predispose the surgeon to glove
      perforation. A barbed suture was developed that is self-anchoring, requiring no
      knots or slack management for wound closure. The elimination of knot tying may
      have advantages over conventional wound closure methods. METHODS: This
      prospective, randomized, controlled trial was designed to show that the use of
      barbed suture in dermal closure of the Pfannenstiel incision during nonemergent
      cesarean delivery surgery produces scar cosmesis at 5 weeks that is no worse than
      that observed with conventional closure using 3-0 polydioxanone suture. Cosmesis
      was assessed by review of postoperative photographs by a blinded, independent
      plastic surgeon using the modified Hollander cosmesis score. Secondary endpoints
      included infection, dehiscence, pain, closure time, and other adverse events.
      RESULTS: The study enrolled 195 patients, of whom 188 were eligible for analysis.
      Cosmesis scores did not significantly differ between the barbed suture group and
      the control group. Rates of infection, dehiscence, and other adverse events did
      not significantly differ between the two groups. Closure time and pain scores
      were comparable between the groups. CONCLUSIONS: The barbed suture represents an
      innovative option for wound closure. With a cosmesis and safety profile that is
      similar to that of conventional suture technique, it avoids the drawbacks
      inherent to suture knots.

PMID- 16651951
TI  - Bilateral lumbar hip dermal fat rotation flaps: a novel technique for autologous
      augmentation gluteoplasty.
AB  - BACKGROUND: The present study reports a novel technique for augmentation and/or
      correction of deformities in the gluteal region. This technique is applicable to
      patients with skin excess, skin flaccidity, and/or ptosis, and for redundant skin
      folds in the lower back region, that often occur following the surgical treatment
      of morbid obesity. METHODS: In a retrospective review, nine female patients, aged
      27 to 64 years, underwent the bilateral lumbar hip dermal fat rotation flaps
      procedure for gluteal augmentation. The patients were observed over a period of 3
      months to 4 years. Gluteal projection was measured with a standardized computed
      tomographic scan in two patients. Complications were analyzed. RESULTS: The
      postoperative photographs and the measurements taken by computed tomographic scan
      proved that the gluteal projection had been increased satisfactorily with this
      innovative procedure. Three complications were observed, the major one being a
      hematoma that required reoperation. CONCLUSION: Bilateral lumbar hip dermal fat
      rotation flaps is an ultimate technique that should be performed in selected
      patients to create a harmonic autologous augmentation of the buttocks region.
      Although the complication rate of this technique was high, it was similar to that
      in some authors' reports for belt lipectomy.

PMID- 16651952
TI  - Biocompatibility of two novel dermal fillers: histological evaluation of implants
      of a hyaluronic acid filler and a polyacrylamide filler.
AB  - BACKGROUND: Several biomaterials are currently available for soft-tissue
      augmentation. Biocompatibility is an indispensable condition for any such
      product. Appropriate histologic evaluation is a prerequisite for understanding
      the responses of tissues to implant materials. Recently, hyaluronic acid and
      polyacrylamide gel products have been introduced as dermal fillers. Both types of
      product are widely considered to be biocompatible. METHODS: The present study
      compared tissue responses in a rat in vivo model (n = 80) to a hyaluronic acid
      filler (Restylane Perlane; Q-Med AB, Uppsala, Sweden) and a polyacrylamide gel
      filler (Aquamid; Contura SA, Montreux, Switzerland). Four groups were evaluated:
      group 1 (n = 20) received the Restylane Perlane implant, group 2 received the
      Aquamid implant (n = 20), group 3 comprised a placebo group (n = 20), group 4 was
      the control group (n = 20). Responses and biocompatibility were assessed by
      histopathologic and histomorphometric evaluations between 1 week and 8 months
      after implantation. RESULTS: The two products induced very different tissue
      responses. The polyacrylamide gel filler was highly bioactive, undergoing cell
      infiltration and integration into tissues. The hyaluronic acid filler underwent
      minimal cell infiltration, and the product remained surrounded by a uniformly
      thin capsule. CONCLUSIONS: This study reveals that two soft-tissue fillers
      considered to be biocompatible induce very different tissue reactions. This
      indicates that their behavior in clinical practice is likely to be different.

PMID- 16651953
TI  - Abdominoplasty and abdominal contour surgery: a national plastic surgery survey.
AB  - BACKGROUND: According to the American Society for Aesthetic Plastic Surgery's
      2004 Cosmetic Surgery National Data Bank, during the last 7 years, the number of
      abdominoplasty procedures performed has increased 344 percent. A national report
      on abdominoplasty has not been since 1977. Grazer and Goldwyn's study reflects
      the preliposuction era of abdominal contouring surgery. The purpose of this study
      was to assess current trends in abdominal contouring techniques and associated
      procedures and the incidence of their complications. METHODS: The study was
      designed as a descriptive correlation survey evaluating the frequency of various
      abdominal contour techniques and complications among 3300 randomly chosen members
      of the American Society of Plastic Surgeons. There were 497 respondents, for a
      response rate of 15 percent. RESULTS: A total of 20,029 procedures were reported
      in the survey; 35 percent (n = 7010) were liposuction of the abdomen, 10 percent
      (n = 2003) were limited abdominoplasties, and 55 percent (n = 11,016) were full
      abdominoplasties. Survey data covered the plastic surgeon's demographics,
      techniques, and incidence of complications during a 12-month period. CONCLUSIONS:
      The authors report the largest series of local and systemic complication rates
      and compare them with those of previously published abdominoplasty surveys. With
      respect to full abdominoplasty, lower complication rates for deep vein thrombosis
      (0.04 percent) and pulmonary embolus (0.02 percent) were seen. No deaths were
      reported. There was no correlation between a surgeon's years in practice and
      complication rates, in concordance with the earlier study by Grazer and Goldwyn.
      Despite more extensive abdominal contouring techniques and the addition of
      liposuction to abdominal contouring, the local and systemic complication rates
      coincided with previous complication rates, as outlined in other studies.

PMID- 16651954
TI  - The evolution of the midface lift in aesthetic plastic surgery.
AB  - The midface lift has recently gained significant popularity with many surgeons.
      It allows the surgeon an opportunity to achieve greater facial harmony with
      facial rejuvenation procedures by correcting midfacial atrophy, addressing the
      tear trough deformity, and correcting the perceived malposition of the malar fat
      pad. This article examines the history of midfacial procedures. Surgical attempts
      at improving the aging face have evolved from minimal excisions and skin closure
      to aggressive dissections at multiple planes. The midface target area is
      peripheral to classic approaches, and its correction has required further
      anterior dissection from a distance or direct access centrally. Ultimately,
      conquering the stigmata of midface aging is entirely related to vectors and
      volume.

PMID- 16651955
TI  - The effect of liposuction and diet on ghrelin, adiponectin, and leptin levels in
      obese Zucker rats.
AB  - BACKGROUND: The fat-regulating hormones, adiponectin, ghrelin, and leptin, have
      been studied extensively with the hope that some therapeutic modality might be
      gleaned from their augmentation or blockade. The authors studied levels of
      ghrelin, adiponectin, and leptin after liposuction in obese male Zucker rats. In
      addition, they altered the fat and carbohydrate content of the rats'
      postoperative diets to determine whether diet affects hormonal levels and/or
      liposuction outcome. METHODS: Thirty-five male, obese Zucker rats were divided
      into four experimental groups. Group I (n = 10) was fed a low-fat/low
      carbohydrate diet; group II (n = 10) was fed a regular chow diet; and group III
      (n = 10) was fed a high-fat/high-carbohydrate diet. Five additional rats served
      as the baseline, unoperated group. The experimental rats underwent subcutaneous
      liposuction, and for 6 weeks they were then fed their experimental diets starting
      on day 0. Experimental rats were euthanized on day 42 and blood was sampled for
      hormonal, triglyceride, and cholesterol levels. RESULTS: Triglyceride levels were
      significantly higher in the high-fat/high-carbohydrate group compared with the
      regular chow and low-fat/low-carbohydrate groups, indicating an effect of diet on
      systemic circulation after liposuction. Ghrelin levels decreased significantly
      and leptin levels demonstrated an increasing trend after liposuction. Adiponectin
      levels did not demonstrate any change with alteration in diet or liposuction.
      CONCLUSIONS: Liposuction may prove to offer patients medically therapeutic
      benefits through hormonal alterations. After liposuction, diet plays an important
      role in weight gain.

PMID- 16651956
TI  - Autologous human fat grafting: effect of harvesting and preparation techniques on
      adipocyte graft survival.
AB  - BACKGROUND: Autogenous fat transfer with lipoinjection for soft-tissue
      augmentation is a commonly used technique without a universally accepted
      approach. The high percentage and variable amount of fat resorption reduce the
      clinical efficacy of this procedure and often result in the need for further
      grafting. The purposes of this study were to evaluate the effect of different
      harvesting and preparation techniques on human fat tissue viability and to
      determine fat tissue viability rates among the different fat preparations
      transplanted into a severe combined immune deficiency mouse model at 3 months.
      METHODS: Using standard liposuction and syringe aspiration, fat was removed from
      patients (n = 3) undergoing elective body contouring. Tissue was prepared by six
      different combinations of centrifugation and/or washing the cells with lactated
      Ringer's solution or normal saline. Metabolic activities of fat cell viability
      were monitored to assess overall cell viability. To analyze viability over 3
      months, freshly harvested tissue specimens (minimum n = 5) were prepared by a
      combination of various procedures (wash, centrifugation, and different solutions)
      and subsequently injected under the dorsal flank skin of severe combined immune
      deficiency mice in two experiments. Mice were monitored for 12 weeks and the fat
      xenografts were removed for mass and histological evaluations. RESULTS: Metabolic
      analyses showed improved cell viability in tissue specimens undergoing minimal
      manipulation. No significant differences in fat cell viability, as assessed by
      graft weight maintenance or histologic evaluations, were observed with regard to
      harvesting or preparation techniques. CONCLUSIONS: Improved viability of freshly
      harvested but untreated fat specimens may be expected as compared with grafts
      that have undergone additional manipulations. No unique combination of
      preparation or harvesting techniques appeared to be more advantageous on
      transplanted fat grafts at 3 months. This study also demonstrated a reliable
      animal model for future investigation into examining novel applications for
      augmenting fat graft survival.

PMID- 16651957
TI  - Adipose aspirates as a source for human processed lipoaspirate cells after
      optimal cryopreservation.
AB  - BACKGROUND: The purpose of this study was to test the authors' hypothesis that
      previously cryopreserved adipose aspirates collected from conventional
      liposuction could still be a reliable source of human processed lipoaspirate
      cells. METHODS: Adipose aspirates were collected from 12 adult female patients
      after conventional liposuction of the abdomen and were then preserved by an
      optimal cryopreservation method with added cryoprotective agents (0.5 M dimethyl
      sulfoxide and 0.2 M trehalose). Cryopreservation of the adipose tissues was
      subsequently conducted with controlled slow cooling and then stored in liquid
      nitrogen (-196 degrees C). One gram of fresh or cryopreserved (after fast
      rewarming) adipose aspirates was processed in vitro and the resulting cell
      pellet, consisting of processed lipoaspirate cells, was cultured separately. The
      length of time until processed lipoaspirate cells became adherent to the culture
      plate was recorded and the number of processed lipoaspirate cells after a 2-week
      culture was counted. RESULTS: Flat, spindle-shape processed lipoaspirate cells
      from the cryopreserved group became adherent to the plate within 48 to 72 hours
      after initial culture compared with the fresh group, where the cells became
      adherent by 24 hours. After a 2-week culture, the cryopreserved aspirates yielded
      an average of 3.7 +/- 1.4 x 10(5) processed lipoaspirate cells per milliliter,
      equal to 90 percent of the yielded number of cells obtained from the fresh
      aspirates (4.1 +/- 1.4 x 10(5) cells/ml). CONCLUSIONS: The authors' results
      indicate that although there is a latency of cell growth after an optimal
      cryopreservation, cryopreserved adipose aspirates can yield a significant number
      of processed lipoaspirate cells compared with fresh aspirates and may be a
      reliable source of human processed lipoaspirate cells because they can still be
      processed later after long-term preservation.

PMID- 16651958
TI  - Rhinoplasty model in rabbit.
AB  - BACKGROUND: Rhinoplasty has become one of the most frequently requested and
      performed surgical procedures for both functional and aesthetic purposes. As an
      attention-attracting prominence, even the slightest disfigurement of the nose
      causes serious disturbance to the patient before or after the operation.
      Functional problems also cause discomfort. For these reasons, postrhinoplasty
      complications are regarded as challenging problems for both for the patient and
      the surgeon. Some cases necessitate grafts for better aesthetic or functional
      outcome, but there is still controversy over the preference for autogenous or
      allogenous grafts, both for primary and secondary cases. Evaluation of autogenous
      and allogenous grafts implanted in the nose is quite challenging for several
      reasons, including the possibility of unpredictable complications leading to
      catastrophic disfigurements, the impossibility of obtaining pathologic specimens,
      and the need for a long follow-up period for stable results. An experimental
      model for rhinoplasty, fulfilling the need for precise evaluation, was planned
      and performed after anatomical observation of the noses of rabbits. METHODS:
      Fifteen adult New Zealand rabbits were used, five for the anatomical evaluation
      and 10 for the rhinoplasty model. Computed tomographic images and measurements
      were obtained before and after the surgical processes. RESULTS AND CONCLUSION:
      This experimental model for rhinoplasty has not been reported in any previous
      studies. This study demonstrates the surgical anatomy of the rabbit in detail and
      constitutes a guide for researchers as a convenient experimental model for
      rhinoplasty, with all stages similar to those performed on humans.

PMID- 16651959
TI  - Prefabricated engineered skin flap using an arteriovenous vascular bundle as a
      vascular carrier in rabbits.
AB  - BACKGROUND: The authors previously described induction of spontaneous tissue
      generation by implanting a collagen matrix and a ligated pedicle (arteriovenous
      bundle) into a hollow porous chamber in vivo in the rabbit. They hypothesized
      that increased tissue volume could be obtained by the application of basic
      fibroblast growth factor (bFGF) and/or by increasing the chamber size and
      porosity. METHODS: In rabbits, a saphenous arteriovenous pedicle and a collagen
      sponge were inserted into a porous chamber in the groin. Small-volume pore
      chambers (experiment 1, n = 7) and larger-volume, wider pore chambers (experiment
      2, n = 13) were compared, and each was compared with and without bFGF. An
      additional three flaps of experiment 2 with bFGF were skin grafted,
      microsurgically transplanted to the ear, and evaluated at 6 months for stability.
      RESULTS: All patent chambers grew tissue; chambers with bFGF were almost filled,
      and those without were only half-filled. Histomorphometric analysis confirmed a
      significant difference. The larger-volume, larger-pore chambers produced more
      than twice the volume of tissue as the smaller chambers did, and this was
      significant. Tissue volume in both the control and bFGF groups of experiment 2
      was significantly greater than that in the respective groups of experiment 1.
      Histology, angiography, and scanning electron microscopy confirmed greater
      vascularity in the bFGF groups and demonstrated vascular connections penetrating
      the chamber pores linking with angiogenic sprouts, probably from the vasa vasorum
      of the pedicle, to contribute to new growth. Transplanted flaps survived and
      appeared normal 6 months later. CONCLUSIONS: Patent pedicles, bFGF, large pore
      size, and larger-volume chambers all seemed to contribute to increased tissue
      growth in this model. The tissue is stable long term.

PMID- 16651960
TI  - An investigation to optimize angiogenesis within potential dermal replacements.
AB  - BACKGROUND: Acute and chronic wounds are costly and invariably expose significant
      structures. Surgical reconstruction causes donor-site morbidity, scarring, and
      the need for intensive care. Reconstruction using an artificial dermis avoids
      donor sites, but available collagen-based solutions are susceptible to poor take.
      Using an in vitro angiogenic assay, the authors investigated dermal matrices for
      potential inclusion in a second-generation proangiogenic synthetic dermal
      replacement. METHODS: Human placental endothelial cells were cocultured on
      Cytodex beads (Pharmacia Biotech) and plated in eight different extracellular
      matrix gels (collagen, fibrin, four glycosaminoglycans, vitronectin, and
      fibronectin), with or without stimulation from two soluble angiogenic factors.
      Three different cell lines were used, with 30 beads per condition. Cellular
      invasion into gels was calculated using Sigma Scan computer software, and
      statistical comparisons were made. RESULTS: The authors found that fibrin
      provided greatest stimulus for endothelial invasion, with invasion in fibrin
      inhibited by collagen in a concentration-dependent fashion. Invasion by
      alternative extracellular matrix components and soluble angiogenic factors was
      far less than that in fibrin. CONCLUSIONS: The authors identified that
      extracellular matrices can provide greater angiogenic potential than soluble
      angiogenic factors. Fibrin provided a better proangiogenic scaffold than
      collagen. This could well be used to encourage blood vessel ingress and eventual
      take of a second-generation proangiogenic synthetic dermal replacement.

PMID- 16651961
TI  - Intracranial volume changes in craniosynostotic rabbits: effects of age and
      surgical correction.
AB  - BACKGROUND: The premature fusion of one or more cranial sutures, termed
      craniosynostosis, alters normal brain growth patterns and results in compensatory
      changes in the cranial vault. The authors previously reported that bilateral
      coronal suture fusion resulted in a reduction in intracranial volume in a rabbit
      model of nonsyndromic, familial coronal suture synostosis. METHODS: The current
      follow-up study involved collecting cross-sectional three-dimensional computed
      tomographic head scans from 142 rabbits (70 normal, 44 with uncorrected
      synostosis, and 28 synostosed rabbits with coronal suturectomy) at 0, 10, 25, 42,
      84, and 126 days of age. Intracranial contents were reconstructed, and indirect
      intracranial volume was calculated. RESULTS: Results revealed a significant (p <
      0.05) postsynostotic reduction of intracranial volume (23 percent) by 25 days of
      age in rabbits with uncorrected craniosynostosis compared with normal controls,
      which continued through 84 days of age. Also, rabbits with surgically released
      synostosis, using a simple strip suturectomy, showed significantly (p < 0.05)
      greater intracranial volume at 25 days of age compared with unoperated synostosed
      rabbits. However, no changes in intracranial volume were noted between 42 and 84
      days of age in rabbits with surgically released synostosis, at which point their
      intracranial volume was 30 percent less than that in normal control rabbits.
      CONCLUSIONS: These data suggest that in rabbits with uncorrected
      craniosynostosis, compensatory changes in the neurocranium were not capable of
      compensating for the loss of sutures as growth sites. The results also showed
      that that surgical release of the synostosed suture improved intracranial volume
      in the short term (25 to 42 days) but failed to change it in the long term (42 to
      84 days), possibly because of rapid resynostosis of the suturectomy site. This
      study suggests that surgical release of the suture fusion site alone may not be
      adequate to allow for normal intracranial volume growth in synostotic rabbits.
      For this reason, it may be efficacious to design and develop adjunct protein and
      gene therapies to prevent resynostosis and improve postoperative intracranial
      volume in craniosynostotic individuals.

PMID- 16651962
TI  - Face transplant: is it worth it?

PMID- 16651963
TI  - Camptodactyly as a spectrum of congenital deficiencies: a treatment algorithm
      based on clinical examination.
AB  - BACKGROUND: Camptodactyly is a frequent congenital hand disorder, but its cause
      and treatment remain a matter of controversy. Although it is difficult to
      establish the primary cause of camptodactyly, careful clinical examination allows
      the assessment of all the structures involved (e.g., skin, subcutaneous fascia,
      flexor tendons, extensor tendon, intrinsic muscles, and joints). The purpose of
      the study was to assess the validity of an algorithm based on the clinical
      examination in planning the operation. METHODS: An algorithm based on clinical
      examination and the authors' 27-year experience was designed to determine and
      customize the surgery for each case according to the function of the anatomical
      structures involved. The authors compared the results of surgical treatment in
      two groups of patients with camptodactyly of the fifth finger operated on before
      (group 1, 33 patients) or after use of the algorithm (group 2, 35 patients). All
      patients had more than 1 year of follow-up (range, 21 to 47 months). RESULTS:
      There were significantly fewer failures in group 2 (14 percent versus 45.5
      percent, p < 0.01). The improvement, after an extensive liberation in stiff early
      cases (type Ia), gave better results than previous attempts but did not reach
      significance (84 percent versus 66 percent). Similarly, for types Ib (early and
      correctable) and IIb (late and correctable) camptodactyly, the surgical results
      were improved, with 91 percent and 90 percent improvement, respectively, in group
      2 versus 50 percent and 44 percent in group 1 (not significant). CONCLUSION: A
      selective surgical indication, based on careful clinical examination, improves
      the results of camptodactyly treatment by correcting the involved anatomical
      components.

PMID- 16651964
TI  - Immediate partial great toe transfer for the reconstruction of composite defects
      of the distal thumb.
AB  - BACKGROUND: Thumb defects distal to the interphalangeal joint do not cause any
      disability; therefore, any consideration to reconstruct the thumb is governed by
      the lifestyle and cultural background of the patient. This study presents the
      excellent results achieved by immediate partial great toe-to-hand transfer to
      reconstruct acute composite defects of the distal thumb. METHODS: Fifty-three
      patients with amputation or crush injury of the distal thumb who underwent
      partial great toe-to-hand transfer at the authors' institute over an 11-year
      period were reviewed. Based on the amputation level of the distal thumb, the
      authors classified the injuries into three groups. Operative techniques used were
      osteo-onychocutaneous flap with partial or whole toenail from the great toe and
      partial great toe transfer with arthrodesis of the interphalangeal joint. Overall
      results were evaluated in terms of success rate, incidence of emergency
      reexploration, and number and type of secondary operation. Static two-point
      discrimination, range of motion, pinch strength, and subjective satisfaction were
      also evaluated. RESULTS: The success rate of immediate partial great toe-to-hand
      transfer was 100 percent. The incidence of inflammation and the reexploration
      rate were not significantly different from those in previously reported articles.
      In 35 cases where postoperative follow-up was possible, static two-point
      discrimination, total active range of motion, and pinch strength were generally
      excellent and the majority of the patients were satisfied with the final outcome.
      CONCLUSION: Immediate reconstruction with partial great toe transfer is an
      excellent option for reconstruction of composite defects of the distal thumb, not
      only for aesthetic reasons but also for functional purposes.

PMID- 16651965
TI  - The thenar index: an objective assessment and classification of thenar atrophy
      based on static hand imprints and clinical implications.
AB  - BACKGROUND: The aims of this study were to test the effectiveness of the
      subjective clinical evaluation and to search for any possibility of constituting
      an objective assessment system for the diagnosis of thenar atrophy based on
      static hand imprints. METHODS: Static hand imprints were obtained from normal
      subjects (group A, n = 116) and carpal tunnel syndrome patients with thenar
      atrophy (group B, n = 26). Thenar index and the bilateral thenar index ratio were
      defined. Cutoff values were considered by analyses with receiver operating
      characteristic curves. RESULTS: No statistically significant difference could be
      demonstrated in thenar index values of dominant and nondominant hands between
      genders and age groups (p > 0.05). A statistically significant difference was
      observed between severity groups in group B (p < 0.05). There was a statistically
      significant difference between thenar index and bilateral thenar index ratio
      values of groups A and B (p < 0.05). Cutoff values were considered a thenar index
      of 31 and a bilateral thenar index ratio of 0.8, which revealed acceptable
      specificity (95.3 percent) and sensitivity (77.4 percent). A new quantitative
      classification for thenar atrophy severity is proposed. CONCLUSIONS:
      Understanding the true onset and natural progression of thenar atrophy can only
      be anticipated with the aid of an objective assessment system. Currently, this
      method should be regarded as a system for patient records and comparison for
      presurgical and postsurgical data. The authors believe that the thenar index
      classification has some merit for future use. It seems that additional objective
      and scientific evaluation systems and novel approaches are still needed to
      demystify the true nature of carpal tunnel syndrome.

PMID- 16651966
TI  - Split flexor carpi ulnaris transfer: a new functioning free muscle transfer with
      independent dual function.
AB  - BACKGROUND: A functioning free muscle transfer is a well-established modality of
      restoring upper limb function in patients with significant functional deficits.
      Splitting the neuromuscular compartments of the free muscle based on its
      intramuscular neural anatomy and using each compartment for a different function
      would allow for restoration of two functions instead of one at the new distant
      site. METHODS: The authors previously reported on the clinical use of a pedicled
      split flexor carpi ulnaris muscle transfer. They now report the use of this
      muscle as a functioning free split muscle transfer to restore independent thumb
      and finger extension in a patient with total extensor compartment muscle loss in
      the forearm and a concomitant high radial nerve avulsion injury. RESULTS: Nine
      months postoperatively, the patient was able to extend his thumb and fingers
      independent of each other. CONCLUSION: This is the first report of a functioning
      free split muscle transfer demonstrating two independent functions in the upper
      limb.

PMID- 16651967
TI  - The hatchet flap for reconstruction of fingertip amputations.
AB  - BACKGROUND: Emmett has described a single triangular flap that contains a partial
      skin bridge on one of its sides and called it the hatchet flap. It was
      successfully used for defects located on various body parts. The aim of this
      study was to present the authors' experience and results obtained with this flap
      in fingertip amputations. METHODS: Nine patients who have completed their 1-year
      follow-up period were included in the study. Two-point discrimination and
      stiffness were tested, and the patients were queried about the existence of cold
      intolerance, hypersensitivity, numbness, and pain in the early (3 months) and
      late (1 year) postoperative periods. RESULTS: The amputations were located on the
      thumb in three patients, index finger in one patient, middle finger in three
      patients, and ring finger in two patients. The average defect size was 2.1 x 1.5
      cm. Partial wound dehiscence was observed in one patient. The flap has provided
      good protective padding and aesthetic contour for the fingers. All incisions
      healed with inconspicuous scars. Average two-point discrimination was 6.3 mm
      (range, 4 to 8 mm). Cold intolerance was observed in two (22.2 percent) and
      paresthesia in one patient (11.1 percent). Joint stiffness was not noted. Most
      patients could return to their normal routine in approximately 4 to 5 weeks.
      CONCLUSIONS: The hatchet flap is a good alternative for transverse and lateral
      oblique fingertip amputations and valuable for volar oblique amputations (defects
      <2 cm) with more extensive flap designs. The technique is simple and safe and
      provides good protective padding and acceptable tactile gnosis.

PMID- 16651968
TI  - Orthognathic surgery in juvenile rheumatoid arthritis patients.
AB  - BACKGROUND: Mandible advancement osteotomy in juvenile rheumatoid arthritis
      patients for class II anterior open-bite malocclusion is controversial; however,
      there is no literature discussing outcomes of surgery in this group of patients.
      An evaluation of such outcomes was undertaken at The Hospital for Sick Children.
      METHODS: A retrospective chart review revealed that eight patients with juvenile
      arthritis underwent orthognathic surgery during a period of 5 years. All of the
      patients had a bilateral sagittal split osteotomy of the mandible, six had a
      simultaneous Le Fort I osteotomy, and four had an additional advancement
      genioplasty. The age of the patients at the time of surgery ranged between 17 and
      22 years (mean, 18 years), with three male patients and five female patients. The
      patients were under follow-up for a minimum of 8 months after surgery, and
      measurements were performed studying preoperative and postoperative lateral
      cephalometric radiographs. RESULTS: All patients have an improved occlusion and
      improved facial aesthetics. One patient continued to suffer from
      temporomandibular joint pain. The mean mandible advancement was 9.6 mm (range,
      3.9 to 18.3 mm). The mean mandible relapse after surgery was 2.1 mm (range, 1 to
      3.1 mm). No exacerbation of the juvenile rheumatoid arthritis was encountered as
      a result of the surgical procedure. CONCLUSIONS: Orthognathic surgery in juvenile
      rheumatoid arthritis patients improves the patient's occlusion, facial
      aesthetics, and therefore quality of life. The relapse rate postoperatively did
      not significantly affect the clinical outcome, and the authors recommend
      orthognathic surgery for this patient population. Future presurgical plans in
      this patient population will include a small posterior open bite and positioning
      the incisors edge to edge to allow for some postoperative relapse.

PMID- 16651969
TI  - Combined transcutaneous transethmoidal/transorbital approach for the treatment of
      medial orbital blowout fractures.
AB  - BACKGROUND: The transcutaneous transorbital approach to medial orbital wall
      fractures facilitates placing a large implant or autogenous graft. However, its
      major disadvantage is the difficulty of accurately reducing the fractured medial
      orbital wall and herniated soft tissues with minimal morbidity. METHODS: To
      resolve this problem, a combined transcutaneous transethmoidal/transorbital
      approach through the same skin incision was developed at the Chonnam National
      University Medical School. Between 1997 and 2003, this approach was used in 54
      patients with pure medial orbital blowout fractures. All fractures were larger
      than 2 cm in defect size and had 3 mm or more of bone displacement. RESULTS:
      Postoperative computed tomographic scans showed complete release of entrapped
      soft tissues and accurate reconstruction of bone defects in all cases.
      Complications related to the operation such as intraorbital and intramuscular
      hemorrhage, infection, and eyeball and optic nerve injuries were not observed,
      except in two cases with slight implant displacement. Follow-up ranged from 2 to
      22 months, with an average of 9 months. Forty-one patients were evaluated 6
      months or more after their reconstructive procedure. At the time of surgery,
      diplopia was present in 39 patients, eyeball movement limitation in 35 orbits,
      and enophthalmos of more than 2 mm in 16 orbits. Postoperatively, diplopia and
      eyeball movement limitation were resolved in most cases. Two patients had
      persistent diplopia for more than 1 year after surgery, and one of these needed
      extraocular muscle surgery. Enophthalmos of more than 2 mm developed in three
      orbits, but enophthalmos of more than 3 mm was not observed in any orbit.
      Cosmetic results at the incision site were acceptable in all patients.
      CONCLUSIONS: The combined transcutaneous transethmoidal/transorbital approach is
      a safe procedure that can be performed with minimal morbidity; it offers the
      advantages of both the transcutaneous approach and the trans-nasal approach.
      Therefore, the authors suggest that this method be considered as a surgical
      alternative for the treatment of medial orbital blowout fractures, especially
      large and combined fractures of the medial wall and other parts of the orbit.

PMID- 16651970
TI  - Improved malar projection with transconjunctival hydroxyapatite granules.
AB  - BACKGROUND: Augmentation of the zygomatic body enhances appearance and provides a
      more youthful look. Porous hydroxyapatite granules offer an alternative to
      alloplastic implants. METHODS: Hydroxyapatite granules were placed by means of a
      transconjunctival approach into subperiosteal malar pockets (n = 8). From the
      preoperative, postoperative, and 1-year follow-up lateral views, malar projection
      was measured as the right angle distance from the point of malar prominence to
      the nasale-subnasale line. RESULTS: Patients were either very satisfied (six of
      eight) or satisfied (two of eight). Malar projection was significantly improved
      postoperatively and was maintained after 1 year. CONCLUSION: This technique,
      performed for cosmetic and reconstructive indications, resulted in measurable
      improvement in malar projection, minimal complications, and optimal patient
      satisfaction.

PMID- 16651971
TI  - Calvarial thickness and its relation to cranial bone harvest.
AB  - BACKGROUND: The purpose of this study was to define the variability in skull
      thickness from location to location and from individual to individual in a large
      number of human skulls. METHOD: Skull thickness was measured in multiple areas of
      the calvaria in 281 dry skulls from the Hamman-Todd osteological collection
      (Cleveland Museum of Natural History, Cleveland, Ohio). A total of 40 points were
      determined over the frontal, occipital, and parietal bones, with a higher number
      of points concentrated on the latter. Repeated measures analysis of variance
      models were used to assess the effects of covariates (individual variables) on
      skull thickness and location. RESULT: A statistically significant pattern of
      increased thickness toward the posterior parietal bones was seen in all
      subgroups. The mean thickness of the skull across all locations was 6.32 mm (SEM,
      0.07 mm) and ranged from 5.3 mm (SEM, 0.09 mm) to 7.5 mm (SEM, 0.09 mm). Age was
      not found to be a significant predictor of mean skull thickness. Differences
      between male and female skulls were greater toward the rear of the parietal
      bones. CONCLUSION: The thickest area of the skull is the parasagittal posterior
      parietal area in male skulls and the posterior parietal area midway between the
      sagittal and superior temporal line in female skulls. An accurate map of the
      skull thickness representing the normative data of the studied population was
      developed. It is hoped that this topographic map will assist the surgeons in
      choosing the safest area of cranial bone graft harvest, thus increasing the
      safety of the procedure.

PMID- 16651972
TI  - Minimally invasive zygoma reduction.
AB  - BACKGROUND: It is universally accepted that zygoma reduction is one of the best
      strategies for facial contouring for Asian patients, and many studies have been
      conducted regarding this subject. However, these studies have continued to
      perform the zygoma reduction by sectioning the complete malar eminence to fix it
      into a new location, which requires a wide range of periosteum dissection to
      expose the bone sufficiently for correct osteotomy. METHODS: In this study, with
      the help of a new instrument, the authors have applied a new minimally invasive,
      blind technique to zygoma reduction with multiple scoring and molding. The
      minimally invasive zygoma reduction was performed through a 5-mm intraoral stab
      incision, and the authors have operated on over 271 male and female patients.
      RESULTS: As a result, the authors could reduce the operation time and the
      postoperative swelling and have achieved greater cosmetic effects and enlarged
      indications compared with those of conventional methods. The well-known
      complications of cheek drooping, facial nerve injury, temporomandibular joint
      injury, and malunion were absent. In particular, because of the relatively
      reduced swelling, most of the patients could resume activities of daily life
      within 3 days after the operation. CONCLUSION: Therefore, the authors recommend
      this new minimally invasive zygoma reduction as another option for zygoma
      reduction.

PMID- 16651973
TI  - Free fibula bone wedge technique for mandible reconstruction using fibula
      osteocutaneous flaps.

PMID- 16651974
TI  - Bilateral cleft lip and whistling deformity: the X flap procedure for its
      correction.

PMID- 16651975
TI  - Formation of the philtral column using vertical interdigitation of orbicularis
      oris muscle flaps in the secondary cleft lip.

PMID- 16651976
TI  - Platysma suspension and platysmaplasty during neck lift: anatomical study and
      analysis of 30 cases.
AB  - BACKGROUND: The authors developed a technique for the treatment of the cervical
      area during face lifts. The authors called this technique platysma suspension and
      platysmaplasty rather than plication. METHODS: After an anatomical study on 10
      corpses on which the authors tested the various platysma suspension techniques,
      they carried out platysma suspension associated with platysmaplasty in 30
      patients. RESULTS: This technique consists of suspending the free edge of the
      platysma muscle and fixing it to a resistant tissue close to the earlobe (Lore's
      fascia or tympanoparotid fascia). The anterior triangle of the neck was well
      defined, and there was no need to undermine the platysma muscle because of a
      perfect sliding plane between the platysma and sternocleidomastoid muscles.
      CONCLUSIONS: This technique is both simple and effective. It generates long
      lasting results, without the inconveniences or complications associated with
      other techniques.

PMID- 16651978
TI  - A new method of costal cartilage harvest for total auricular reconstruction: part
      I. Avoidance and prevention of intraoperative and postoperative complications and
      problems.
AB  - BACKGROUND: The occurrence of chest wall deformity is not dependent on the amount
      of costal cartilage harvested but results from the method of costal cartilage
      harvest. Therefore, the authors developed a new method of costal cartilage
      harvest where the perichondrium is left completely intact at the donor site and
      the remaining costal cartilage after fabrication of the three-dimensional costal
      cartilage framework is returned to the perichondrial pocket to fill the dead
      space formed. By leaving the perichondrium completely intact, the most ideal
      environmental condition for regeneration of cartilage is attained. METHODS: The
      costal cartilages are harvested en bloc with the perichondrium left completely
      intact at the donor site. After fabrication of the three-dimensional frame, the
      remaining costal cartilage is cut into small blocks that act as spacers to fill
      the dead space formed in the perichondrial pocket. RESULTS: The findings of the
      authors' study involving over 270 cases performed with the new method of costal
      cartilage harvest revealed that there were absolutely no postoperative chest wall
      deformities identified, and there was a significant decrease in intraoperative
      complications. CONCLUSION: The authors' study revealed that the new method of
      costal cartilage harvest plays an important role in the regeneration of cartilage
      and in the prevention and avoidance of postoperative chest wall deformity.

PMID- 16651979
TI  - Clinical application of cultured autologous human auricular chondrocytes with
      autologous serum for craniofacial or nasal augmentation and repair.
AB  - BACKGROUND: The repair of a craniofacial or nose deformity requires a large
      volume of reconstructive material. A conventional cartilage graft does not
      provide a sufficient volume of reconstructive material. Therefore, augmentation
      of the facial form to the defect shape is quite difficult. The authors developed
      a new treatment method that provides a sufficiently large volume of
      reconstructive material and enables an easier reconstruction of the original
      shape. METHODS: Ages of the patients ranged between 9 and 63 years. Approximately
      1 cm of auricular cartilage was collected from the auricular concha. Isolated
      chondrocytes were cultured with autologous serum that accelerates cell
      proliferation. The cells were subcultured and formed a gel-form mass. This mass,
      together with autologous serum, was grafted (injected) on the periosteum and into
      the subcutaneous pocket. The volume of grafted cultured chondrocytes ranged from
      1.7 to 40 cc (1 to 5 x 10(7) cells/cc). The lesion changed from soft gel form
      into hard cartilage tissues within 2 to 3 weeks and stabilized. RESULTS:
      Excellent or good satisfactory results were obtained in all patients and have
      been maintained for periods ranging from 3 to 34 months. No patient experienced
      absorption of cultured chondrocytes. Biopsy of the newly formed tissues showed
      that it was an elastic cartilage derived from the original tissue. CONCLUSIONS: A
      small number of chondrocytes obtained from a 1-cm auricular cartilage are
      successfully cultured into a large number of cells in a gel form. Those
      autologous auricular chondrocytes in a gel form allow for the repair of
      complicated shapes of the defect area. This technique is applicable to various
      treatments for craniofacial or nose deformity.

PMID- 16651981
TI  - Composite anterolateral thigh-fascia lata flap: a good alternative to radial
      forearm-palmaris longus flap for total lower lip reconstruction.
AB  - BACKGROUND: Major defects of the lower lip are challenging to the reconstructive
      surgeon. The major goals in treating total lower lip defects are reconstruction
      of the external skin and mucosal lining and maintenance of oral competence and
      sphincter function. The authors describe reconstruction of total lower lip and
      larger full-thickness defects including the cheek and commissure by means of a
      composite anterolateral thigh-fascia lata free flap. METHODS: The flap was
      harvested with 5-cm fascial extensions at the superior and inferior margins. The
      flap was folded over the fascia lata to restore the intraoral lining and cover
      the external skin defect. Fascia lata extensions were divided longitudinally into
      two fascial strips at both margins of the flap. Two strips were tunneled through
      the orbicularis muscle in the upper lip and sutured to each other and to the
      orbicularis muscle. The remaining two strips were anchored to the zygomatic bone
      periosteum by permanent sutures. This procedure was used in 11 patients. RESULTS:
      In all cases, disease was advanced squamosus cell carcinoma. The patients' ages
      ranged from 37 to 72 years. Nine patients had cancer of the lower lip and two
      patients had a buccal cancer involving the lip. The entire lower lip, bilateral
      modiolus, and part of the cheek were resected in all patients, and mandibulectomy
      was performed in three patients. Flap survival was 100 percent. One patient died
      10 days after the operation because of cardiopulmonary arrest. At the end of the
      1-year follow-up period, all patients had good oral continence at rest and had
      achieved sufficient oral competence when eating. Eight patients were able to
      resume a regular diet and two patients could eat a soft diet. CONCLUSIONS: This
      flap is a good choice for reconstruction of the extensive head and neck defects.
      We think that anterolateral thigh-fascia lata composite flap has maximum
      reconstructive capacity and minimal donor-site morbidity. This flap has many
      advantages over the radial forearm flap and should replace to the composite
      radial forearm palmaris longus tendon flap when total lower lip reconstruction is
      concerned.

PMID- 16651982
TI  - Immunohistochemical differentiation and localization analysis of sweat glands in
      the adult human axilla.
AB  - BACKGROUND: The classic concept of axillary glands differentiates between eccrine
      glands, producing abundant clear, nonodorous sweat; and apocrine glands,
      excreting small amounts of turbid, odorous milky sweat. A third type of sweat
      glands, the "apoeccrine" glands, were recently identified. To define the
      different types of sweat glands and their location and number, the authors
      carried out a prospective histologic study on adult human axillary skin,
      including various immunohistochemical markers. METHODS: Forty-three consecutive
      Caucasian, subjectively normhidrotic patients, who underwent a surgical procedure
      in the axilla unrelated to the axillary glands, were included in the study. For
      verification of normhidrosis, the gravimetric test was carried out by measuring
      the amount of sweat secretion per minute. Then, a 1 x 1-cm measuring piece of
      skin and subcutaneous tissue was excised in the apex of the axilla, divided into
      three samples--altogether, 129 samples--and processed for histologic examination.
      RESULTS: In the dermis, the authors found only very few eccrine (average, 0.3
      gland/cm in only 12 percent of all patients) and apocrine glands (average, 0.1
      gland/cm in only 4.7 percent of patients), and no apoeccrine glands in any
      patient. In the subcutaneous tissue, the mean number of glands per centimeter
      squared was 10 for the eccrine glands, nine for the apocrine glands, and six for
      the apoeccrine glands. CONCLUSIONS: In the authors' Caucasian subjects, all or
      most of the sweat glands were found in the subcutaneous tissue near the border to
      the dermis and not in the dermis. For extremely hyperfunctioning sweat glands,
      the authors recommend less radical surgical methods, with the preservation of
      skin, based on the knowledge that most glands are localized in the subcutaneous
      tissue.

PMID- 16651983
TI  - A review of vascular injection techniques for the study of perforator flaps.
AB  - BACKGROUND: With a new era of flap surgery, additional anatomical information is
      required. The relatively recent interest in musculocutaneous perforator flaps has
      once again sparked interest in the vascular anatomy of surgical flaps. There are
      a variety of anatomical techniques available to define the vascular anatomy of
      tissues of interest. In this article, the authors review vascular injection
      techniques available and describe the technique currently used in their
      laboratory. METHODS: A comprehensive review of vascular injection techniques is
      summarized. Barium sulfate and lead oxide in particular are reviewed in detail.
      RESULTS: This article reviews the historical development of vascular injection
      techniques, outlines current investigative methods, and expands on a radiopaque
      lead oxide and gelatin injection method that provides high-quality angiograms.
      CONCLUSIONS: The standard method for the study of perforator flap is the lead
      oxide-gelatin technique. However, other methods can provide complementary
      information on vascular anatomy.

PMID- 16651984
TI  - Using the descending branch of the lateral femoral circumflex vessel as a source
      of two independent flaps.
AB  - BACKGROUND: Simultaneous reconstruction of two separate defects by two free flaps
      is time consuming and often requires two donor sites. The anterior and lateral
      aspect of the thigh is an ideal donor site for free tissue harvest without
      incurring significant morbidity. In this article, the authors describe their
      recently developed technique that allows for harvesting two independent
      fasciocutaneous free flaps from the same descending branch of lateral circumflex
      femoral vessel as a new clinical application of the versatile anterolateral thigh
      flap. METHODS: A total of eight flaps were developed from left thighs of four
      patients. There were two male and two female patients, with a mean age of 42.0
      years. The defects were either on the lower extremity (n = 2) or in the oral
      cavity (n = 2). Each anterolateral aspect of the thigh was used to develop two
      perforator flaps, based on one perforator each. The anterolateral thigh flap was
      elevated in the standard manner based on at least two cutaneous vessels of the
      descending branch of the lateral circumflex femoral artery. The skin flaps were
      tailored to the recipient site requirement and the main descending branches of
      the lateral femoral circumflex vessels were divided in between to be used as the
      pedicle of both flaps. The mean flap dimensions ranged from 2.5 x 4 cm to 8 x 12
      cm (mean, 5 x 8 cm). The mean operation time was 11 hours 30 minutes. The mean
      length of the pedicle was 9 cm (ranged, 8 to 11 cm). The mean external diameter
      of the descending branch in the mid thigh and where it joined to the lateral
      circumflex femoral artery was 1.75 mm and 3 mm, respectively. Three donor sites
      were closed directly and one was grafted. RESULTS: All flaps survived completely.
      No complications were encountered. Donor-site morbidity was negligible.
      Hospitalization averaged 9.9 +/- 1.7 days. CONCLUSION: Two fasciocutaneous flaps
      based on independent skin vessels can be reliably harvested from the same
      descending branch of the lateral femoral circumflex artery for simultaneous
      reconstruction of two separate defects.

PMID- 16651985
TI  - The use of a pain pump for optimal postoperative pain management.

PMID- 16651986
TI  - On the ethics of composite tissue allotransplantation (facial transplantation).

PMID- 16651987
TI  - The root of all evil.

PMID- 16651992
TI  - Arterial supply to type II muscle after fasciocutaneous free flap transfer.

PMID- 16651993
TI  - Flow-through anterior thigh flaps with a short pedicle.

PMID- 16651994
TI  - Randomized controlled trials in plastic surgery.

PMID- 16651996
TI  - Surgical technique for the correction of postpalatoplasty fistulae of the hard
      palate.

PMID- 16651999
TI  - Extending the reach of the heterodigital arterialized flap.

PMID- 16652000
TI  - What causes eyelid bags?

PMID- 16652001
TI  - Unusual facial impalement injury with wooden material.

PMID- 16652003
TI  - Sideburn flap for temple reconstruction.

PMID- 16652004
TI  - An easy way to create a subcutaneous tunnel and deliver the nerve graft across
      the face for reconstruction of facial palsy.

PMID- 16652005
TI  - Parotid duct fistula: an unusual complication of epidermoid (sebaceous) cyst
      excision.

PMID- 16652006
TI  - Performance of the surgeon during suction-assisted lipectomy.

PMID- 16652007
TI  - In situ-generated vascularized fibula free flap for the reconstruction of
      complete mandibular defects.

PMID- 16652008
TI  - Permanent pressure alopecia after microsurgical breast reconstruction.

PMID- 16652009
TI  - Breast cancer recurrence following delayed reconstruction detected within the
      latissimus dorsi flap and locoregional tissue.

PMID- 16652010
TI  - Iterative wound dehiscence in augmentation mammaplasty as a systemic side effect
      of hidden topical corticotherapy.

PMID- 16652011
TI  - Early complication with the use of polyurethane-covered breast implants.

PMID- 16652012
TI  - Preventing "T" junction dehiscence in mammaplasty.

PMID- 16652013
TI  - Breast ptosis: to augment, to lift, or to do both?

PMID- 16652014
TI  - Pectoralis major hemiosseous flap for paradoxical respiration.

PMID- 16652015
TI  - Hypospadias with urethral quadruplication.

PMID- 16652016
TI  - The proximal phalanx: another option to harvest a skin graft for skin defects on
      the fingers.

PMID- 16652017
TI  - Is diabetes mellitus type 2 a risk factor for Dupuytren's contracture in the
      Mediterranean region?

PMID- 16652018
TI  - Don't smoke warnings on thermoplastic hand splints.

PMID- 16652019
TI  - Pyoderma gangrenosum associated with multiple sclerosis.

PMID- 16652020
TI  - Accentuated varicella eruption: a complication of Q-switched alexandrite laser
      treatment.

PMID- 16652021
TI  - Augmentation brachioplasty.

PMID- 16652022
TI  - Does Egyptian foot present an increased risk of ingrown toenail?

PMID- 16652023
TI  - The grid layer system for mapping of the rat cremaster muscle flap
      microcirculation.

PMID- 16652024
TI  - A simple device to reliably facilitate "stripping" of a closed-suction drainage
      tube.

PMID- 16652025
TI  - Same-session multiple procedures in office-based surgery: a warning for the
      growing and dangerous field of office surgery.

PMID- 16652026
TI  - HIV/hepatitis C virus-coinfected patients with normal alanine aminotransferase
      levels.
AB  - BACKGROUND AND AIMS: The significance of normal alanine aminotransferase (ALT)
      levels in patients with HIV/hepatitis C virus (HCV) coinfection is not well
      understood. METHODS: We performed a cross-sectional retrospective analysis on
      consecutive HIV/HCV-coinfected patients (n = 89) who underwent a liver biopsy
      during a 2-year period. Similar data were also collected on HCV-monoinfected
      patients (n = 117). RESULTS: Mean ALT levels and the percentage of patients with
      normal ALT (< or =40 U/L) levels were similar in HIV/HCV-coinfected (mean +/- SD,
      81.7 +/- 56.1 U/L; 21%) and HCV-monoinfected patients (97.3 +/- 100.7 U/L; 18%; P
      = 0.19 and 0.54, respectively). Coinfected patients, however, had significantly
      advanced necroinflammation (P= 0.001) and fibrosis (P = 0.02) compared with
      monoinfected patients. The percentage of patients with advanced necroinflammation
      (grades 3 or 4) was lower in HCV-monoinfected patients with normal ALT levels
      compared with those with elevated ALT (5% vs 20%, respectively). In contrast, the
      percentage of coinfected patients with advanced necroinflammation was similar
      whether the patient had normal or elevated ALT levels (32% vs 37%, respectively).
      CONCLUSIONS: In coinfected patients, normal ALT levels are not an indicator of
      mild necroinflammation and may not portend a more benign disease course.

PMID- 16652027
TI  - Intestinal lymphocyte subsets and turnover are affected by chronic alcohol
      consumption: implications for SIV/HIV infection.
AB  - We recently demonstrated that simian immunodeficiency virus (SIV) viral loads
      were significantly higher in the plasma of rhesus macaques consuming alcohol
      compared with controls following intrarectal SIV infection. To understand the
      possible reasons behind increased viral replication, here we assessed the effects
      of chronic alcohol consumption on distribution and cycling of various lymphocyte
      subsets in the intestine. Macaques were administered alcohol (n = 11) or sucrose
      (n = 12), and percentages of memory and naive and activated lymphocyte subsets
      were compared in the blood, lymph nodes, and intestines. Although minimal
      differences were detected in blood or lymph nodes, there were significantly
      higher percentages of central memory (CD95+CD28+) CD4+ lymphocytes in the
      intestines from alcohol-receiving animals before infection compared with
      controls. In addition, higher percentages of naive (CD45RA+CD95-) as well as
      CXCR4+CD4 cells were detected in intestines of alcohol-treated macaques.
      Moreover, alcohol consumption resulted in significantly lower percentages of
      effector memory (CD95+CD28-) CD8 lymphocytes as well as activated Ki67+CD8 cells
      in the intestines. A subset (7 receiving alcohol and 8 receiving sucrose) were
      then intrarectally inoculated with SIV(mac251). Viral RNA was compared in
      different tissues using real-time PCR and in situ hybridization. Higher levels of
      SIV replication were observed in tissues from alcohol-consuming macaques compared
      with controls. Central memory CD4 lymphocytes were significantly depleted in
      intestines and mesenteric lymph nodes from all alcohol animals at 8 weeks
      postinfection. Thus, changes in the mucosal immune compartment (intestines) in
      response to alcohol are likely the major reasons behind higher replication of SIV
      observed in these animals.

PMID- 16652028
TI  - Dominant ex vivo cross-stimulation of CD8+ T-cells with whole soluble gag protein
      in HIV-infected subjects.
AB  - BACKGROUND: Soluble HIV proteins are often used to detect HIV-specific CD4+ T
      helper cell responses in vitro. However, exogenous antigens can also indirectly
      stimulate CD8+ T-cells and thus complicate assessment of CD4+ T-cell responses.
      OBJECTIVE: To analyze the extent of in vitro HIV-1 Gag p55 protein cross
      stimulation to CD8+ T-cells in therapy-naive and highly active antiretroviral
      therapy (HAART)-treated HIV patients and to correlate this phenomenon with HIV
      disease progression. METHODS: Gag protein-stimulated T-cell responses were
      measured in total and CD8-depleted peripheral blood mononuclear cells (PBMCs) by
      interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays in 20
      therapy-naive and 60 HAART-treated HIV patients. Numbers of spot forming cells
      (SFCs) relative to CD4+ and CD8+ T-cell subsets were calculated. Gag protein
      stimulated responses were correlated with markers of disease progression.
      RESULTS: Stimulation of PBMC with HIV-1 Gag protein induced higher CD8+ T-cell
      responses than CD4+ T-cell responses in both therapy-naive and HAART-treated HIV
      patients (P < 0.001). Gag protein cross-stimulation of CD8+ T-cells was higher in
      therapy-naive than in HAART-treated HIV patients (P < 0.001). In HAART-treated
      HIV patients, we detected an inverse correlation between Gag protein cross
      stimulation of CD8+ T-cells and the CD4 count (R = -0.311; P = 0.016). Depletion
      of CD14+ cells abrogated the responses, suggesting that Gag protein cross
      stimulation of CD8+ T-cells depends on antigen processing and presentation by
      antigen-presenting cells (APCs). CONCLUSIONS: HIV protein cross-presentation to
      CD8+ T-cells should be taken into account when detecting HIV-specific T-cell
      responses by stimulation of PBMCs with whole exogenous antigens.

PMID- 16652029
TI  - Evaluation of p24-based antiretroviral treatment monitoring in pediatric HIV-1
      infection: prediction of the CD4+ T-cell changes between consecutive visits.
AB  - Worldwide, 700,000 infants are infected annually by HIV-1, most of them in
      resource-limited settings. Care for these children requires simple, inexpensive
      tests. We have evaluated HIV-1 p24 antigen for antiretroviral treatment (ART)
      monitoring in children. p24 by boosted enzyme-linked immunosorbent assay of
      heated plasma and HIV-1 RNA were measured prospectively in 24 HIV-1-infected
      children receiving ART. p24 and HIV-1 RNA concentrations and their changes
      between consecutive visits were related to the respective CD4+ changes. Age at
      study entry was 7.6 years; follow-up was 47.2 months, yielding 18 visits at an
      interval of 2.8 months (medians). There were 399 complete visit data sets and 375
      interval data sets. Controlling for variation between individuals, there was a
      positive relationship between concentrations of HIV-1 RNA and p24 (P < 0.0001).
      While controlling for initial CD4+ count, age, sex, days since start of ART, and
      days between visits, the relative change in CD4+ count between 2 successive
      visits was negatively related to the corresponding relative change in HIV-1 RNA
      (P = 0.009), but not to the initial HIV-1 RNA concentration (P = 0.94).
      Similarly, we found a negative relationship with the relative change in p24 over
      the interval (P < 0.0001), whereas the initial p24 concentration showed a trend
      (P = 0.08). Statistical support for the p24 model and the HIV-1 RNA model was
      similar. p24 may be an accurate low-cost alternative to monitor ART in pediatric
      HIV-1 infection.

PMID- 16652030
TI  - Pharmacokinetic drug interactions between opioid agonist therapy and
      antiretroviral medications: implications and management for clinical practice.
AB  - BACKGROUND: Opioid dependence and HIV/AIDS are 2 of the most serious yet
      treatable diseases worldwide. Global access to opioid agonist therapy and HIV
      treatment is expanding but when concurrently used, problematic pharmacokinetic
      drug interactions can occur. METHODS: We reviewed English, Spanish, French, and
      Italian language articles from 1966 to 2005 in Medline using the following
      keywords: HIV, AIDS, HIV therapy, antiretroviral therapy, HAART, drug
      interactions, methadone, and buprenorphine. Additionally, we reviewed abstracts
      from national and international meetings and conference proceedings. Selected
      references from these articles were reviewed as well. RESULTS: Clinical case
      series and carefully controlled pharmacokinetic interaction studies have been
      conducted between methadone and most approved antiretroviral therapies. Important
      pharmacokinetic drug interactions have been demonstrated within each class of
      agents, affecting either methadone or antiretroviral agents. Few studies,
      however, have been conducted with buprenorphine. The metabolism of both
      therapies, description of the known interactions, and clinical implications and
      management of these interactions are reviewed. CONCLUSIONS: Certain interactions
      between methadone and antiretroviral medications are known and may have important
      clinical consequences. To optimize care, clinicians must be alert to these
      interactions and have a basic knowledge regarding their management.

PMID- 16652031
TI  - Primary HIV drug resistance and efficacy of first-line antiretroviral therapy
      guided by resistance testing.
AB  - BACKGROUND: Primary HIV drug resistance has been associated with poor treatment
      outcome of first-line highly active antiretroviral therapy (HAART) in several
      trials. The aim of the study was to assess the efficacy of first-line HAART
      guided by resistance testing. METHODS: In a prospective multicenter study in the
      state of Nordrhein-Westfalen, Germany, chronically HIV-infected patients
      underwent genotypic resistance testing and were monitored for 48 weeks after
      initiation of HAART. RESULTS: Primary drug resistance was found in 30 of 269
      patients entering the study between January 2001 and December 2003 [11.2%; 95%
      confidence interval, 7.4-14.9]. In intent-to-treat analysis, the proportion of
      patients with viral load below 50 copies/mL after 24 and 48 weeks was 70.0% and
      66.7%, respectively, in patients with resistance and 74.1% and 73.6%,
      respectively, in patients without (P = 0.66 and 0.51). In on-treatment analysis,
      the proportions were 80.8% and 83.3%, respectively, in patients with resistance
      and 81.9% and 85.0%, respectively, in patients without (P= 0.79 and 0.77). These
      results were also valid considering a detection limit of 400 copies/mL.
      CONCLUSIONS: The prevalence of primary drug resistance was 11.2% in chronically
      HIV-infected patients. HAART guided by resistance testing had similar efficacy in
      patients with primary drug resistance as compared with patients with wild-type
      virus. Based on these facts, resistance-adapted first-line HAART is suggested as
      routine practice.

PMID- 16652032
TI  - Mixed patterns of changes in central and peripheral fat following initiation of
      antiretroviral therapy in a randomized trial.
AB  - INTRODUCTION: Although peripheral fat loss is a consistent feature of HIV
      associated lipodystrophy, less is known about whether changes in central and
      peripheral fat occur in tandem or independently over time. We examined
      intraindividual changes in dual-energy x-ray absorptiometry (DEXA) and
      anthropometry data over 64 weeks after initiation of antiretroviral therapy
      (ART). METHODS: In ACTG 384, ART-naive subjects were randomized to receive
      didanosine and stavudine or zidovudine and lamivudine plus efavirenz, nelfinavir,
      or both. In the metabolic substudy A5005S (N= 329), waist, hip, thigh, and arm
      circumferences were measured in triplicate. DEXA scanning was performed in 157
      subjects. RESULTS: Individual changes in limb and trunk fat at week 64 correlated
      positively (R =.72, P <.001). Most subjects had directionally concordant changes
      in limb and trunk fat (36% gained and 32% lost in both regions). In 26%, trunk
      fat increased while limb fat decreased, whereas the reverse occurred in only 6%
      (P <.001). Changes in waist and hip circumferences also correlated positively (R
      =.62, P <.001). The proportion of subjects with waist/hip ratio more than .95
      (men) or .90 (women) was 34% at baseline and 47% at week 64 (P =.003). In those
      who developed increased waist/hip ratio, 76% had increased waist circumference.
      CONCLUSIONS: Individual results obtained by both anthropometry and DEXA show
      diverse patterns of fat gain and loss over 64 weeks after initiation of ART, but
      changes tended to occur in the same direction. Increased waist/hip ratio was
      predominantly associated with increased waist circumference. There was no
      evidence that central fat accumulation and peripheral fat loss are linked in most
      subjects.

PMID- 16652033
TI  - Efficacy and safety of a once-daily fixed-dose combination of abacavir/lamivudine
      compared with abacavir twice daily and lamivudine once daily as separate entities
      in antiretroviral-experienced HIV-1-infected patients (CAL30001 Study).
AB  - BACKGROUND: A one-tablet, once-daily abacavir/lamivudine fixed-dose combination
      (FDC) has been recently approved to treat HIV-1 infection. METHODS: A randomized,
      open-label, parallel-group, multicenter study to compare the efficacy and safety
      of the FDC group to the separate entities (SE) group, in combination with
      tenofovir and a new protease inhibitor or nonnucleoside reverse transcription
      inhibitor in antiretroviral-experienced adults experiencing virologic failure
      (VF). Eligible subjects had viral loads >1000 copies/mL with < or =3 nucleoside
      reverse transcription inhibitor-associated mutations. The primary efficacy end
      point was time-average changed from baseline (average area under the curve minus
      baseline) in plasma HIV-1 RNA over 48 weeks. RESULTS: A total of 186 subjects
      were enrolled. The average area under the curve minus baseline was -1.65 and 
      1.83 log10 copies/mL in the FDC and SE groups, respectively (intention to treat;
      95% confidence interval: -0.13, 0.38). Patients in the FDC (50%) and SE groups
      (47%) achieved viral loads <50 copies/mL based on the time to loss of virologic
      response algorithm. VF was low and similar in both groups (FDC, 16%; SE, 18%).
      Tolerability was similar between the 2 groups. CONCLUSIONS: The FDC group had
      noninferior efficacy over 48 weeks to the SE group in treatment-experienced
      subjects with VF.

PMID- 16652034
TI  - Evaluation of a low-cost method, the Guava EasyCD4 assay, to enumerate CD4
      positive lymphocyte counts in HIV-infected patients in the United States and
      Uganda.
AB  - OBJECTIVE: To evaluate the EasyCD4 assay, a less expensive method to enumerate
      CD4+ lymphocytes, in resource-limited settings. DESIGN: Cross-sectional study
      conducted in the United States and Uganda. METHODS: We compared CD4+ cell counts
      obtained on replicate samples from HIV-infected patients by the EasyCD4 assay, a
      microcapillary flow-based system, and by standard flow cytometry or FACSCount
      with linear regression and the Bland-Altman method. RESULTS: Two hundred eighteen
      samples were analyzed (77 in the United States and 141 in Uganda). In the United
      States, mean +/- SD CD4 was 697 +/- 438 cells/microL by standard flow cytometry
      and 688 +/- 451 cells/microL by EasyCD4. In Uganda, the mean +/- SD CD4 was 335
      +/- 331 cells/microL by FACSCount and 340 +/- 327 cells/microL by EasyCD4. The 2
      methods were highly correlated (US cohort, r2 = 0.97, slope = 1.0, intercept = 
      18; Ugandan cohort, r2 = 0.92; slope = 0.95; intercept = 23). The mean
      differences in CD4 cell counts were 9.0 and -4.6 cells/microL for the US and
      Ugandan cohorts, respectively, and they were not significant in either cohort. In
      the Ugandan cohort, sensitivity and specificity of the EasyCD4 for CD4 below 200
      cells/microL were 90% and 98%, respectively. Positive predictive value was 96%;
      negative predictive value was 93%. CONCLUSIONS: Our results suggest that EasyCD4
      may be used with high positive and negative predictive value in resource-limited
      settings.

PMID- 16652035
TI  - A comparison of genital HIV-1 shedding and sexual risk behavior among Kenyan
      women based on eligibility for initiation of HAART according to WHO guidelines.
AB  - BACKGROUND: Guidelines for initiating antiretrovirals are based on markers of
      advanced disease and are not directly linked to markers of HIV-1 transmission
      such as viral shedding. METHODS: We evaluated genital HIV-1 shedding and risk
      behavior among 650 antiretroviral-naive women stratified by WHO criteria for
      initiating antiretrovirals based on CD4 count and symptoms. RESULTS: Genital HIV
      1 concentrations increased in stepwise fashion with declining CD4 counts and the
      presence of symptoms. Compared with the reference group (asymptomatic with CD4
      >350 cells/microL), those with advanced immunosuppression (CD4 <200 cells/microL)
      had significantly higher cervical HIV-1 RNA concentrations (2.4 log10 copies/swab
      vs. 3.8 log10 copies/swab, P < 0.001). However, women with CD4 counts <200
      cells/microL were also less likely than the reference group to report intercourse
      during the past week (58% vs. 26%, P < 0.001). CONCLUSIONS: Antiretroviral
      guidelines focusing on individuals with the most advanced immunosuppression will
      target those with the highest genital HIV-1 concentrations. However, individuals
      with less advanced immunosuppression also have high levels of genital HIV-1 and
      may be more sexually active. The effect of increased antiretroviral availability
      on the spread of HIV-1 might be enhanced by extending treatment, in addition to
      other risk reduction services, to those with less advanced disease.

PMID- 16652036
TI  - Heterosexually transmitted HIV infection among African Americans in North
      Carolina.
AB  - CONTEXT: Rates of heterosexually transmitted HIV infection among African
      Americans in the southeastern United States greatly exceed those for whites.
      OBJECTIVE: Determine risk factors for heterosexually transmitted HIV infection
      among African Americans. METHODS: Population-based case-control study of black
      men and women, aged 18-61 years, reported to the North Carolina state health
      department with a recent diagnosis of heterosexually transmitted HIV infection
      and age- and gender-matched controls randomly selected from the state driver's
      license file. A lower-risk stratum of respondents was created to identify
      transmission risks among people who denied high-risk behaviors. RESULTS: Most
      case subjects reported annual household income < $16,000, history of sexually
      transmitted diseases, and high-risk behaviors, including crack cocaine use and
      sex partners who injected drugs or used crack cocaine. However, 27% of case
      subjects (and 69% of control subjects) denied high-risk sexual partners or
      behavior. Risk factors for HIV infection in this subset of participants were less
      than high school education (adjusted odds ratio [OR] 5.0; 95% CI: 2.2, 11.1),
      recent concern about having enough food for themselves or their family (OR 3.7;
      1.5, 8.9), and having a sexual partner who was not monogamous during the
      relationship with the respondent (OR 2.9; 1.3, 6.4). CONCLUSION: Although most
      heterosexually transmitted HIV infection among African Americans in the South is
      associated with established high-risk characteristics, poverty may be an
      underlying determinant of these behaviors and a contributor to infection risk
      even in people who do not have high-risk behaviors.

PMID- 16652037
TI  - Trends in AIDS and mortality in HIV-infected subjects with hemophilia from 1985
      to 2003: the competing risks for death between AIDS and liver disease.
AB  - OBJECTIVE: To study trends in progression to AIDS, all-cause mortality, and cause
      specific mortality (AIDS-related, liver disease, and hemorrhagic complications)
      over calendar periods with different exposure to highly active antiretroviral
      therapy (HAART) in a cohort of hemophiliacs in Spain, taking into account the
      competing risks of the causes of death. METHODS: Multicenter cohort of HIV
      infected hemophiliacs. HIV seroconversion was estimated using mathematic
      techniques for interval-censored data from 1979 through 1985. Rates of AIDS and
      cause-specific death were calculated by Poisson regression, allowing for late
      entry, for the periods 1985 through 1992, 1993 through 1996, 1997 through 2000
      (early HAART), and 2001 through 2003 (late HAART), also allowing for competing
      risks. RESULTS: Of 585 subjects, 44% were younger than 15 years of age, 82% had
      severe hemophilia, 86% had type A hemophilia, and the median seroconversion date
      was October 1982. Calendar period and age at HIV seroconversion strongly
      influenced AIDS and death rates. Compared with 1993 through 1996, decreases of
      75% (relative risk [RR] = 0.25, 95% confidence interval [CI]: 0.14 to 0.43) and
      72% (RR = 0.28, 95% CI: 0.12 to 0.63) in the RR of AIDS were observed in early
      and late HAART. For all-cause mortality, 72% (RR = 0.28, 95% CI: 0.18 to 0.42)
      and 83% (RR = 0.17, 95% CI: 0.09 to 0.33) decreases were observed by 1997 through
      2000 and 2001 through 2003. For liver-related deaths, increases were observed in
      the late-HAART period (RR = 2.80, 95% CI: 0.94 to 8.36) compared with 1993
      through 1996, but using competing risks, this RR was substantially reduced (RR =
      1.70, 95% CI: 0.57 to 5.04). DISCUSSION: Major reductions in AIDS and death rates
      were observed from 1997 to 2003 in hemophiliacs. These survival improvements are
      largely attributable to decreases in AIDS-related deaths and have been
      accompanied by increases in liver disease death rates, which are overestimated if
      competing risks are not taken into account.

PMID- 16652038
TI  - Potential impact of antiretroviral therapy on HIV-1 transmission and AIDS
      mortality in resource-limited settings.
AB  - OBJECTIVE: To estimate the potential impact of antiretroviral therapy on the
      heterosexual spread of HIV-1 infection and AIDS mortality in resource-limited
      settings. METHODS: A mathematic model of HIV-1 disease progression and
      transmission was used to assess epidemiologic outcomes under different scenarios
      of antiretroviral therapy, including implementation of World Health Organization
      guidelines. RESULTS: Implementing antiretroviral therapy at 5% HIV-1 prevalence
      and administering it to 100% of AIDS cases are predicted to decrease new HIV-1
      infections and cumulative deaths from AIDS after 10 years by 11.2% (inter
      quartile range [IQR]: 1.8%-21.4%) and 33.4% (IQR: 26%-42.8%), respectively. Later
      implementation of therapy at endemic equilibrium (40% prevalence) is predicted to
      be less effective, decreasing new HIV-1 infections and cumulative deaths from
      AIDS by 10.5% (IQR: 2.6%-19.3%) and 27.6% (IQR: 20.8%-36.8%), respectively.
      Therapy is predicted to benefit the infected individual and the uninfected
      community by decreasing transmission and AIDS deaths. The community benefit is
      greater than the individual benefit after 25 years of treatment and increases
      with the proportion of AIDS cases treated. CONCLUSIONS: Antiretroviral therapy is
      predicted to have individual and public health benefits that increase with time
      and the proportion of infected persons treated. The impact of therapy is greater
      when introduced earlier in an epidemic, but the benefit can be lost by residual
      infectivity or disease progression on treatment and by sexual disinhibition of
      the general population.

PMID- 16652039
TI  - Sexual risk reduction for persons living with HIV: research synthesis of
      randomized controlled trials, 1993 to 2004.
AB  - OBJECTIVE: To conduct a meta-analytic review of interventions to reduce HIV
      individuals' sexual risk. DESIGN: Studies were included if they examined a
      deliberate sexual risk-reduction strategy in a sample that included HIV
      participants, used a randomized controlled trial design, measured condom use or
      number of sexual partners after the intervention, and provided sufficient
      information to calculate effect size (ES) estimates. METHOD: Reports were
      gathered from computerized databases, by contacting individual researchers, by
      searching relevant journals and conference proceedings, and by reviewing
      reference sections of obtained papers. Data from 15 studies (N = 3234
      participants) available as of November 30, 2004 were included. ES estimates were
      standardized mean differences. RESULTS: Across the studies, intervention
      participants exhibited lowered sexual risk relative to control participants on
      condom use (mean ES = 0.16, 95% confidence interval [CI]: 0.08 to 0.25) but not
      for number of sexual partners (mean ES = -0.01, 95% CI: -0.16 to 0.14).
      Interventions were more successful at increasing condom use if the sample
      included fewer men who have sex with men (MSM) or younger participants and when
      interventions included motivational and skills components. CONCLUSIONS:
      Behavioral interventions reduced sexual risk especially if they included
      motivational and skills components. Such interventions have been less effective
      for older samples, suggesting the need for further refinement to enhance their
      efficacy. Motivation-and skill-based interventions have not yet been tested with
      HIV MSM who, in general, seem to have benefited less from extant risk-reduction
      interventions.

PMID- 16652040
TI  - Prevalence of HIV in the US household population: the National Health and
      Nutrition Examination Surveys, 1988 to 2002.
AB  - To examine trends in HIV prevalence in the US household population, serum or
      urine samples from 2 National Health and Nutrition Examinations Surveys (NHANES)
      (1988-1994 and 1999-2002), were tested for HIV antibody. In the 1999 to 2002
      survey, data on risk behaviors, CD4 T lymphocytes, and antiretroviral therapy
      (ART) were also available. In the 1988 to 1994 survey, there were 59 positive
      individuals of 11,203 tested. In NHANES 1999 to 2002, there were 32 positive
      individuals of 5926 tested. The prevalence of HIV infection among those aged 18
      to 39 years in NHANES 1988 to 1994 was 0.38% (95% confidence interval [CI]: 0.22
      0.68) as compared with 0.37% (95% CI: 0.17 to 0.80) in 1999 to 2002. Prevalence
      did not change significantly between surveys in any race and/or ethnic or gender
      group among 18- to 39-year-old participants. HIV prevalence was 3.58% (95% CI:
      1.88 to 6.71) among non-Hispanic blacks in the 40- to 49-year-old age group in
      1999 to 2002, but the age range available in NHANES 1988 to 1994 was 18 to 59
      years and does not allow direct comparison of prevalence. Cocaine use and the
      presence of herpes simplex virus-2 antibody were the only significant risk
      factors for HIV infection for non-Hispanic blacks. Fifty-eight percent of
      infected individuals not reporting ART had CD4 T-lymphocyte counts < 200
      cells/mm3 compared with 18.2% on therapy and 12.5% of participants newly informed
      of their HIV status.

PMID- 16652041
TI  - HIV prevalence, sociodemographic, and behavioral correlates and recruitment
      methods among injection drug users in St. Petersburg, Russia.
AB  - OBJECTIVE: In St. Petersburg, Russia, we sought to describe the characteristics
      of active high-risk injection drug users (IDUs) to evaluate the associations
      between behavioral and demographic characteristics and HIV-1 infection and to
      describe 3 discrete recruitment methods. METHODS: Active high-risk IDUs were
      recruited in 3 ways: through street outreach, at facilities serving IDUs, and by
      network-based chain referral. Recruits were screened, counseled, and tested for
      HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was
      analyzed as a function of sociodemographic and behavioral variables. RESULTS:
      During the 10-month recruitment period, data from 900 participants were
      collected: median age was 24 years, and in the previous month, 96% used heroin
      and 75% shared needles with others. The baseline HIV prevalence was 30% (95%
      confidence interval [CI]: 27 to 33). Recruitment through social networks was the
      most productive strategy. HIV-positive individuals were younger, but none of the
      other sociodemographic or behavioral characteristics differed significantly by
      HIV status. CONCLUSIONS: The estimated HIV prevalence of 30% places St.
      Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment
      through network-based chain referral is a useful method for recruiting active
      IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to
      be elucidated.

PMID- 16652042
TI  - Molecular epidemiology of HIV-1 infection in a small Brazilian county: usefulness
      of envelope and polymerase sequences to epidemiologic studies.
AB  - OBJECTIVE: The AIDS epidemic in Brazil is spreading from the large urban centers
      to small counties and the innermost parts of the country; however, data on the
      features of HIV-1 infection in these places are scarce. To study the routes of
      HIV-1 spread and assess the existence of transmission networks in such a setting,
      we performed a genetic analysis of viral sequences from the small county of
      Miracema, Rio de Janeiro State. METHODS: HIV-1 envelope and polymerase sequences
      recovered from 63 adult patients (from a cohort of 78 patients) were
      phylogenetically analyzed. RESULTS: A polyphyletic pattern ensued. Six clusters
      of sequences sharing close genetic relatedness were also recovered from 29 (46%)
      patients. Envelope and polymerase phylogenies yielded essentially the same
      results. CONCLUSIONS: The polyphyletic pattern suggests multiple viral
      introductions in the region. Intracluster cases, including those with no known
      direct epidemiologic link, probably took part in the same chain of viral
      transmission. Such a pattern suggests the existence of sexual networks and the
      emergence of multiple new infections within a relatively short period, a
      potential molecular marker of high incidence.

PMID- 16652043
TI  - Sexually transmitted infection services as a component of HIV care: findings of a
      demonstration project among HIV-infected women in Thailand.
AB  - OBJECTIVES: As Thailand scales up its antiretroviral treatment program, the role
      of sexually transmitted infection (STI) services to prevent HIV transmission has
      not been addressed. We provided STI services for HIV-infected women as a
      component of HIV care and assessed STI prevalence and risk behaviors. METHODS:
      HIV-infected women attending an infectious disease clinic and an STI clinic in
      Bangkok were screened for the presence of genital ulcers by visual inspection,
      for gonorrhea and chlamydial infection by polymerase chain reaction, for
      trichomoniasis by wet mount, and for syphilis by serology. Women were asked about
      sexual risk behavior and use of antiretroviral treatment. Risk-reduction
      counseling, condoms, and STI treatment were provided. RESULTS: Two-hundred ten
      HIV-infected women at an infectious disease clinic (n = 150) and an STI clinic (n
      = 60) received STI services from July 2003 through February 2004. The prevalence
      for any STI was 8.0% at the infectious disease clinic and 30.0% at the STI clinic
      (P < 0.01). Of the 116 (55.2%) sexually active women, 42 (36.2%) reported sex
      without a condom during the last 3 months. Women receiving antiretroviral
      treatment reported condom use during last sex more often compared with those not
      receiving antiretroviral treatment (82.2% vs. 58.8%; P = 0.03). CONCLUSION: STIs
      and sexual risk behavior were common among these HIV-infected women, and STI
      services for HIV-infected persons have been expanded to more clinics in Thailand.
      Further analysis of HIV transmission risk is necessary for developing a national
      strategy for prevention of HIV transmission among HIV-infected persons.

PMID- 16652044
TI  - Different methods to calculate the inhibitory quotient of boosted single protease
      inhibitors and their association with virological response.

PMID- 16652045
TI  - Response to Rapatski BL, Suppe F, Yorke JA. HIV epidemics driven by late disease
      stage transmission.

PMID- 16652046
TI  - Genetic characterization of diverse HIV-1 strains in an immigrant population
      living in New York City.
AB  - New York City (NYC) is one of the original foci of the HIV-1 epidemic and has a
      greater number of AIDS cases than any other city in the United States. NYC also
      hosts the highest number of immigrants among the nation's cities: more than 2
      million among a total population of 8 million. Such a high rate of immigration
      could act as a potential source for introducing and disseminating novel HIV-1
      strains into the United States. Our current study focuses on the genetic
      characterization of HIV-1 strains circulating in an immigrant population in NYC.
      Of the 505 HIV-1-positive specimens obtained, 196 were available for viral
      sequencing from the C2 to V3 region of env. Phylogenetic analysis using maximum
      likelihood and neighbor-joining methods demonstrated that non-B subtypes and
      circulating recombinant forms (CRFs) accounted for 43.4% (85 of 196 cases),
      whereas the remaining 56.6% (111 of 196) cases had viral variants similar to the
      typical North American subtype B virus. Of those non-B subtypes and CRFs, subtype
      A and CRF02 dominated (63.5% combined); other subtypes, including C, D, F1, G,
      CRF01_AE, and CRF06_cpx, were also detected. Two HIV-1 sequences do not cluster
      with any known subtypes or CRFs. Furthermore, the distribution of non-B subtypes
      and CRFs was consistent with the countries of origin, suggesting that many of the
      study subjects were likely infected in their home country before they entered the
      United States. Subtype B viruses identified in the immigrant population showed no
      significant differences from the typical North American B subtype, however,
      indicating that a significant proportion of the immigrants must have been
      infected after they came to the United States. Public health officials and
      physicians should be aware of the growing genetic diversity of HIV-1 in this
      country, particularly in areas with sizable immigrant populations.

PMID- 16652047
TI  - Persistent abnormalities in peripheral blood dendritic cells and monocytes from
      HIV-1-positive patients after 1 year of antiretroviral therapy.
AB  - Antiretroviral therapy (ART) has led to marked decreases in morbidity and
      mortality rates among HIV-1-positive patients; however, immune recovery is not
      complete. Although dendritic cells (DCs) were shown to be involved in HIV-1
      pathogenesis, few studies have investigated the effect of ART on DCs. We have
      analyzed the effect of ART on numerical distribution, expression of chemokine
      receptors, and ex vivo production of inflammatory cytokines by peripheral blood
      (PB) monocytes and DCs in a cohort of chronically infected HIV-1-positive
      patients. Patients were tested before therapy and at weeks +2, +4, +8, +12, and
      +52 after starting ART.Our results show an incomplete T-cell immune
      reconstitution in chronically infected patients who had undetectable plasma
      viremia while taking ART for 1 year. This was associated with persistent
      abnormalities at week +52 of ART, corresponding to increased numbers of CD16 DCs
      and monocytes, as well as altered expression of CXC chemokine receptors, in the
      form of increased CXCR1 expression on monocytes and decreased reactivity for
      CXCR2 and/or CXCR4 on myeloid and plasmacytoid DCs. In addition, an abnormally
      high spontaneous ex vivo secretion of inflammatory cytokines by CD16 DCs and
      monocytes was still detected after 1 year of ART. These abnormalities were
      especially pronounced in patients with less than 200 CD4 T cells/microL, which
      could be related to the persistence of undetected viral replication and sustained
      immune activation.

PMID- 16652048
TI  - Evaluation of HIV-1 p24 antigenemia and level of CD8+CD38+ T cells as surrogate
      markers of HIV-1 RNA viral load in HIV-1-infected patients in Dakar, Senegal.
AB  - Alternative, affordable, and simple assays to monitor antiretroviral therapy
      (ART) in resource-poor settings are needed. We have evaluated and compared a heat
      denatured (HD) HIV p24 amplified enzyme-linked immunosorbent assay from Perkin
      Elmer and CD38CD8 T-cell levels, determined by flow cytometry, for their capacity
      to predict viral load (VL) in HIV-1-infected patients from Senegal. Median
      fluorescence intensity (MFI) of CD38 expression on memory (CD45RO) CD8 T cells
      correlated better with RNA VL than HD p24 antigenemia (R = 0.576, P < 0.0001 vs R
      = 0.548, P < 0.0001). MFI of CD38 expression on memory CD8 T cells could predict
      detectable RNA VL (VL = 2.6 log10) with a sensitivity of 87% and a specificity of
      74%. A comparable sensitivity (89%) could be reached for HD p24 assay, but only
      to predict RNA VL of more than 5 logs, which might lead to unacceptable delays in
      clinical decision making. The clinical use of the HD p24 assay to monitor ART in
      Senegal would require more comparative data about the kinetics of p24 antigen and
      HIV RNA in peripheral blood as well as further evaluation regarding its
      sensitivity toward subtype A and CRF02. MFI of CD38 expression on memory CD8 T
      cells appeared to be a better alternative to monitor ART in HIV-infected patients
      from Senegal.

PMID- 16652049
TI  - Safe treatment interruptions in patients with nadir CD4 counts of more than 350
      cells/microL: a randomized trial.
AB  - OBJECTIVE: To evaluate clinical, immunologic, and virologic performance of
      patients with nadir CD4 counts of >350 cells/microL upon treatment interruption.
      DESIGN: Randomized, open-label clinical trial of 48 weeks' duration. METHODS:
      Patients on effective highly active antiretroviral therapy, with nadir CD4 counts
      of >350 cells/microL and peak viral loads of <50,000 copies/mL were randomized to
      continue therapy or to interrupt antiretroviral medication. End points for
      patients with treatment interruption were CD4 counts of <350 cells/microL, viral
      loads of >1 log above the pretherapy values, or clinical symptoms attributable to
      HIV, at which point treatment was restarted. In the continuation group, the end
      points were virologic failure, opportunistic infections, and treatment
      discontinuation due to toxicities. RESULTS: Twenty patients were randomized to
      stop therapy and 16 patients to continue. Median CD4 counts at baseline were 643
      cells/microL for the interruption group and 633 cells/microL for the continuation
      group. No end points were reached in the interruption group. By week 8, viral
      load returned to values comparable to those of pretherapy in all patients in the
      interruption group and remained stable until week 48. CD4 counts dropped in the
      interruption group (median loss of 156 cells/microL) at week 48. Significant
      decreases in venous lactate were observed in the interruption group. CONCLUSIONS:
      Treatment interruptions in patients with nadir CD4 counts of >350 cells/microL
      seem safe for at least 48 weeks. Pretherapy viral load appears as a valuable tool
      to predict its level at week 48.

PMID- 16652050
TI  - Lower genitourinary tract sources of seminal HIV.
AB  - OBJECTIVE: To investigate genital tract sources of HIV-1, we conducted extensive
      genitourinary sampling of 23 seropositive men without urethritis who shed HIV in
      their seminal plasma. DESIGN: Semen was collected, then samples were obtained for
      HIV RNA in blood plasma, urethral fluid, pre-prostate massage fluid/urine (PMF/U)
      and post-PMF/U, and expressed prostatic secretions. Systematic transrectal
      ultrasound-guided prostate biopsies obtained from multiple prostate areas were
      evaluated for HIV RNA and DNA. RESULTS: Seminal HIV RNA levels correlated with
      HIV RNA levels in urethral fluid and post-PMF/U and with prostate biopsies HIV
      DNA, but not with expressed prostatic secretions HIV RNA. However, only the HIV
      RNA level in post-PMF/U independently predicted that in semen (2.77-fold change
      in semen for each 10-fold change in post-PMF/U; 95% confidence interval, 1.0-7.7)
      accounting for one third of the seminal HIV RNA level variation, irrespective of
      adjustment for antiretroviral therapy. CONCLUSIONS: These data indicate that
      distal genitourinary sources other than the prostate appear to be the major
      source of seminal HIV in men without clinical urethritis or prostatitis. Because
      the HIV RNA level in blood plasma is not reliable as an independent clinical
      predictor of virus levels in seminal plasma, these findings also extend the
      concept that the male genital tract is a distinct virological compartment from
      blood.

PMID- 16652051
TI  - Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a
      decade of experience.
AB  - Transmitted resistance to antiretroviral drugs in acute and early HIV-1 infection
      has been well documented, although overall trends vary depending on geography and
      cohort characteristics. To describe the changing pattern of transmitted drug
      resistant HIV-1 in a well-defined cohort in New York City, a total of 361
      patients with acute or recent HIV-1 infection were prospectively studied over a
      decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell
      subsets and HIV-1 RNA levels. The prevalence of overall transmitted resistance
      changed from 13.2% to 24.1% (P = 0.11) during the periods 1995 to 1998 and 2003
      to 2004. Nonnucleoside reverse transcriptase inhibitor resistance prevalence
      increased significantly from 2.6% to 13.4% (P = 0.007) during the same periods,
      whereas prevalence of multidrug-resistant virus shifted from 2.6% to 9.8% (P =
      0.07) but did not achieve statistical significance. A comparable immunologic and
      virologic response of appropriately treated individuals was observed regardless
      of viral drug susceptibility status, suggesting that initial combination therapy
      guided by baseline resistance testing in the case of acute and early infection
      may result in a favorable treatment response even in the case of a drug-resistant
      virus. These data have important implications for selection of empiric first-line
      regimens for treatment of acutely infected antiretroviral-naive individuals and
      reinforce the need for baseline resistance testing in acute and early HIV-1
      infection.

PMID- 16652052
TI  - The 118I reverse transcriptase mutation is the only independent genotypic
      predictor of virologic failure to a stavudine-containing salvage therapy in HIV-1
      infected patients.
AB  - Patients infected with HIV-1 with more than 1000 HIV-1 RNA copies/mL, who were
      genotyped within 3 months before starting stavudine and treated for at least 3
      months with a stable stavudine-containing highly active antiretroviral therapy,
      were selected from our database to identify the determinants of response to
      stavudine. Nonresponse was defined as a failure to achieve HIV-1 RNA level of
      less than 400 copies/mL or a reduction of more than 2 log10 by week 12.
      Univariate logistic analysis was used to elicit the failure-associated reverse
      transcriptase mutations (scored 1 to develop a genotype score). Eighty-one
      patients were eligible for the analysis, including 75 (93%) who previously
      received zidovudine. Thirty-five (43%) were nonresponders. Univariate logistic
      analysis revealed the following failure-associated mutations: 41L (P = 0.0001),
      44D (P = 0.02), 118I (P = 0.0006), 184V (P = 0.04), 210W (P = 0.0004), and 215Y
      (P = 0.002) for a median stavudine score of 2. Failure was observed in 7 (18.9%)
      of 37 patients with a score less than 2, compared with 28 (63.6%) of 44 patients
      with a score of 2 or greater (P < 0.0001). The multivariable analysis showed that
      the 118I mutation (P = 0.04) was the only independent genotypic predictor of
      failing on a stavudine- containing highly active antiretroviral therapy.

PMID- 16652053
TI  - Dyslipidemia among perinatally HIV-infected children enrolled in the PACTS-HOPE
      cohort, 1999-2004: a longitudinal analysis.
AB  - BACKGROUND: Protease inhibitor (PI)-containing regimens have led to improved
      survival among HIV-infected children. However, adverse effects, including
      dyslipidemia, may put children at risk for cardiovascular disease. METHODS: Serum
      cholesterol and triglyceride levels were recorded on perinatally HIV-infected
      children participating in the PACTS-HOPE cohort (1999-2004). Hypercholesterolemia
      (HC) was defined as cholesterol > or =200 mg/dL and hypertriglyceridemia (HT) as
      triglycerides >or =150 mg/dL. HC and HT were modeled over time using generalized
      estimating equations. RESULTS: For 178 children, 47% met criteria for HC and 67%
      for HT at least once during the study period. In generalized estimating equation
      models, PI use, undetectable viral load, and immunologic category 3 were
      independent predictors of HC. HT was significantly associated with PI use and
      body mass index (BMI) > or =90th percentile for age and gender. Among children on
      PI-containing regimens, HC was significantly associated with multiple PIs and
      undetectable viral load; HT was predicted by body mass index > or =90th
      percentile and ritonavir use. The prevalence of clinical lipodystrophy was 5.6%
      (10/178). CONCLUSIONS: Children on PI-containing regimens have a higher risk of
      both HC and HT. Lipid levels should be measured regularly in children on
      antiretroviral treatment. Interventions such as diet, exercise, or lipid-lowering
      drug therapy may benefit some children.

PMID- 16652054
TI  - Pharmacologic optimization of protease inhibitors and nonnucleoside reverse
      transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic
      drug monitoring and adherence support.
AB  - We evaluated the feasibility and effectiveness of therapeutic drug monitoring
      (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in
      patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse
      transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points
      were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound,
      or development of treatment limiting toxicity. One hundred twenty-two patients
      (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks. No
      difference was observed between arms in risk of reaching a study end point or
      between groups of patients with abnormal vs "therapeutic" drug concentrations.
      Interindividual variabilities (coefficient of variation) were the following:
      efavirenz, 77.5%; nevirapine, 74.5%; lopinavir, 73.4%; nelfinavir, 83.7%;
      indinavir, 80.8%; saquinavir, 112.4%. Intraindividual variabilities (median
      coefficient of variation) were the following: NNRTIs, approximately 25%; PIs,
      48.4%. Despite persistently abnormal results in 26 of patients in the AT arm
      (38%), dosage adjustment was only undertaken in 9 patients (35%).A significant
      proportion of patients had drug concentrations outside the therapeutic range. The
      Pharmacologic Optimization of PIs and NNRTIs (POPIN) study confirms that TDM
      trials are complex to interpret and statistically underpowered, with
      effectiveness better assessed through the clinical utility of a TDM result,
      whether normal or abnormal. Although TDM of PIs and NNRTIs may be useful in
      selected patients, routine and unselected use is not supported by current
      evidence.

PMID- 16652055
TI  - Increased incidence of disseminated histoplasmosis following highly active
      antiretroviral therapy initiation.
AB  - To determine whether the initiation of highly active antiretroviral therapy
      (HAART) had any influence on the incidence of disseminated histoplasmosis, a
      retrospective cohort study was performed on 1551 patients followed for up to 12
      years. After controlling for CD4 counts, age, and sex, patients taking HAART for
      2 months or less were more likely to develop disseminated histoplasmosis than
      untreated patients (respectively, hazard ratio, 3.7 [95% confidence interval,
      1.57-8.7]; P = 0.003). In contrast, after 6 months of HAART, treated patients
      were less likely to develop disseminated histoplasmosis than untreated patients
      (hazard ratio, 0.6 [95% confidence interval, 0.37-0.98], P = 0.04). This
      increased incidence suggests that the initiation of HAART and the subsequent
      immune reconstitution may reveal undiagnosed latent disseminated histoplasmosis.

PMID- 16652056
TI  - Predictors of hepatitis C virus RNA levels in a prospective cohort study of drug
      users.
AB  - High levels of hepatitis C virus (HCV) RNA are associated with a poor response to
      treatment of chronic hepatitis C, and a substantial reduction in HCV RNA levels
      predicts a favorable treatment response. We prospectively studied time-dependent
      and time-independent predictors of HCV RNA levels in 264 drug users with chronic
      HCV infection. Interviews on medical history and high-risk behaviors, phlebotomy
      for HIV viral load, serum HCV RNA levels as measured by the COBAS Amplicor HCV
      Monitor (Roche Diagnostics, Branchburg, NJ), and a lymphocyte subset assay were
      performed. Factors associated with HCV RNA levels over time were analyzed using a
      linear mixed model. Nearly 70% of the participants were men, two thirds were
      Hispanic, and the mean age was 46 years. HCV RNA levels increased over time.
      Older age (P < 0.001), HIV seropositivity (P = 0.03), and HCV nongenotype 1 (P =
      0.05) were predictors of higher HCV RNA levels on multivariate analysis. Among
      142 HIV-seropositive participants, a detectable HIV-1 viral load (P < 0.001) and
      recent alcohol use (P = 0.02) were predictors of higher HCV RNA levels. The
      predictors of higher HCV RNA levels found in this longitudinal study are
      consistent with those of prior cross-sectional studies. Further studies are
      warranted to determine if treatment of alcohol use affects HCV RNA levels.

PMID- 16652057
TI  - Factors associated with nonadherence to highly active antiretroviral therapy: a 5
      year follow-up analysis with correction for the bias induced by missing data in
      the treatment maintenance phase.
AB  - This study aimed to identify factors associated with nonadherence during the
      maintenance phase of highly active antiretroviral therapy (months 12-60) in the
      Anti PROtease Cohort (APROCO) cohort after correcting for the bias due to missing
      outcome data. A Heckman 2-stage approach (generalized estimating equations probit
      model) was used to compare visits with moderate or poor adherence and visits with
      high adherence. Between months 12 and 60, at least 1 self-reported adherence
      measure was available for 970 of the 1110 patients with at least 12 months of
      follow-up (3889 visits with adherence assessments). Adherence was rated as high
      at 2466 visits, moderate at 1125, and poor at 298. After adjustment for
      "missingness," moderate and poor adherence were independently associated with age
      (younger), perceived treatment side effects, dosing frequency different from
      twice daily, and a protease inhibitor-based regimen. They were also associated
      with depression and lack of support from the main partner. High adherence was
      most likely among patients born outside the European Union. A comparison
      restricted to poor-adherence and high-adherence visits yielded a similar pattern
      of predictors. Adjusting for missing outcome data changed the predictor set.
      Reasons for nonadherence are multifactorial. Psychosocial interventions and the
      selection of the best-tolerated regimens are needed to improve long-term
      adherence of HIV-infected patients to their lifelong treatment.

PMID- 16652058
TI  - Individual, interpersonal, and structural correlates of effective HAART use among
      urban active injection drug users.
AB  - Among individuals receiving highly active antiretroviral therapy (HAART),
      injection drug users (IDUs) are less likely to achieve HIV suppression. The
      present study examined individual-level, interpersonal, and structural factors
      associated with achieving undetectable plasma viral load (UVL) among US IDUs
      receiving recommended HAART. Data were from baseline assessments of the INSPIRE
      (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4
      site, secondary HIV prevention intervention for heterosexually active IDUs. Of
      1113 study participants at baseline, 42% (n = 466) were currently taking
      recommended HAART (34% were female, 69% non-Hispanic black, 26% recently
      homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic
      regression revealed that among those on recommended HAART, adjusted odds of UVL
      were at least 3 times higher among those with high social support, stable
      housing, and CD4 > 200; UVL was approximately 60% higher among those reporting
      better patient-provider communication. Outpatient drug treatment and non-Hispanic
      black race and an interaction between current drug use and social support were
      marginally negatively significant. Among those with high perceived support,
      noncurrent drug users compared with current drug users had a greater likelihood
      of UVL; current drug use was not associated with UVL among those with low
      support. Depressive symptoms (Brief Symptom Inventory) were not significant.
      Results suggest the major role of social support in facilitating effective HAART
      use in this population and suggest that active drug use may interfere with HAART
      use by adversely affecting social support. Interventions promoting social support
      functioning, patient-provider communication, stable housing, and drug abuse
      treatment may facilitate effective HAART use in this vulnerable population.

PMID- 16652059
TI  - Transitions to injecting drug use among noninjecting heroin users: social network
      influence and individual susceptibility.
AB  - OBJECTIVES: To determine the incidence/predictors of transitions to injecting
      among noninjecting heroin users (NIUs). METHODS: Street-recruited NIUs in New
      York City, March/1996-March/2003, were interviewed for a prospective cohort study
      about social network influence (communication promoting injecting; exposure to
      injectors) and individual susceptibility. A transition to injecting was the first
      drug injection following baseline. Hazards ratios (HRs) (P < 0.05) were estimated
      by Cox proportional hazards regression, stratified by baseline injecting history.
      RESULTS: Of 369 (64% of 579) followed, former-injectors were more likely to
      transition to injecting (33% or 53/160 vs. 12% or 25/209; 16.0/100 person-years
      at-risk [pyar] vs. 4.6/100 pyar; HR = 3.25). Independent predictors among never
      injectors included using > or =2 bags of heroin daily (HR = 7.0); social network
      influence (communication) and homelessness (HR = 6.3); shorter-term heroin use
      (HR = 5.3); social network influence (exposure) and physically abused (HR = 4.7);
      friends approve/condone drug injecting (HR = 3.5); lower perceived social
      distance from injectors (HR = 2.9); and younger age at first heroin use (HR =
      1.2). Independent predictors among former-injectors were social network influence
      (communication) and lower perceived social distance from injectors (HR = 3.4);
      white race/ethnicity (HR = 2.0); not very afraid of needles (HR = 1.8); and
      younger age (HR = 1.1). CONCLUSIONS: The risk of initiating injecting was lower
      than the risk of resuming injecting. Social network influence facilitates
      transitioning to injecting among those susceptible. Interventions to prevent
      injecting should address both social network influence and individual
      susceptibility.

PMID- 16652060
TI  - Mortality in HIV-infected and uninfected children of HIV-infected and uninfected
      mothers in rural Uganda.
AB  - OBJECTIVE: To estimate 2-year mortality rates in HIV-1-infected and uninfected
      infants born to HIV and HIV mothers. METHODS: Data are from a prospective study
      in rural Rakai District, Uganda. Infant HIV status (determined by polymerase
      chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast
      feeding, and maternal HIV viral load and CD4 levels were measured at the
      postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier
      survival analysis were used to assess survival of infants by maternal and infant
      HIV status and by quartiles of viral load. Log-rank tests were used to test the
      equality of survival functions. RESULTS: Of the 4604 pregnant women, 16.9% were
      HIV, and the proportion of children infected was 20.9%. Median survival of HIV
      infected infants was 23 months. Two-year child mortality rates were 128 of 1000
      children born to HIV mothers, 165.5 of 1000 uninfected children born to HIV
      mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with
      children of HIV mothers, the hazard of child mortality was 2.04 (P < 0.001) if
      the mother was HIV and 3.78 (P < 0.001) if the infant was also infected. In the
      adjusted model, the highest quartiles of log10 HIV viral load in infants and
      mothers were associated with significantly increased hazard of child mortality
      (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200
      cells/mL were also significant predictors of child mortality (HR = 2.61). A total
      of 67.6% of HIV-infected children with viral loads above the median died by the
      age of 2 years and are in need of early antiretroviral therapy (ART).
      CONCLUSIONS: More than half of HIV-infected infants died at less than 2 years of
      age. Therefore, ART may need to be initiated earlier in HIV-infected African
      children.

PMID- 16652061
TI  - Higher in utero and perinatal HIV infection risk in girls than boys.
AB  - OBJECTIVE: This study analyzed mother-to-child HIV transmission rates by sex and
      exposure time for babies born to HIV-infected, untreated African women. METHODS:
      Data were analyzed from 2 independent studies done in Malawi during the 1990s.
      Infections were established by polymerase chain reaction on blood samples. Odds
      ratios (ORs) for transmission were examined by period at risk: in utero (infected
      in umbilical cord blood), perinatal (infected in 1st postnatal blood > or =4
      weeks), and postnatal (later postnatal infection). RESULTS: Among 1394 singleton
      births, girls were more likely to become infected than boys. For in utero
      transmission, the OR was 1.4 (95% CI: 0.9 to 2.2). For transmission during early
      life (umbilical cord blood not available) the OR was 2.7 (95% CI: 1.5 to 4.9).
      However, transmission risks in the perinatal and postnatal infection periods did
      not differ in boys and girls. Among 303 tested twin-birth pairs, girls were at
      higher risk than boys for in utero (OR: 2.6; 95% CI: 1.2 to 5.8) and perinatal
      (OR: 1.9; 95% CI: 1.0 to 3.7) infection. Recognized mother-to-child transmission
      risk factors did not explain the higher risk of infection in girls. CONCLUSIONS:
      Girls were at higher risk of early (in utero and perinatal) HIV infection than
      boys. It is proposed that minor histocompatibility reactions between maternal
      lymphocytes and infant Y chromosome-derived antigens reduce the risk of HIV
      transmission in boys.

PMID- 16652062
TI  - Acceptability of routine HIV testing ("opt-out") in antenatal services in two
      rural districts of Zimbabwe.
AB  - Low uptake of prevention of mother-to-child transmission of HIV (PMTCT) services
      in resource-limited settings requires new approaches to prevent missed
      opportunities. Routine HIV testing ("opt-out" testing) in antenatal care (ANC)
      should be considered. An exploratory cross-sectional survey was conducted in 6
      PMTCT sites in rural Zimbabwe. Women who had attended ANC in health centers where
      PMTCT was provided were surveyed in postnatal services. Of 520 women sampled, 285
      (55%) had been HIV tested during their last pregnancy. Primary education or no
      education (P = 0.02), reporting receiving neither group education in the ANC
      clinic (P < 0.001) nor individual pretest counseling (P < 0.001), and having
      attended <6 ANC visits (P < 0.03) were associated with not having been HIV
      tested. Among the 235 women not HIV tested in ANC, 79% would accept HIV testing
      if opt-out testing was introduced. Factors associated with accepting the opt-out
      approach were being <20 years old (P = 0.005), having secondary education or more
      (P = 0.03), living with a partner (P = 0.001), and the existence of a PMTCT
      service where the untested women delivered. Thirty-seven women of 235 (16%) would
      decline routine HIV testing, mainly because of their fear of knowing their HIV
      status and the need to have their partner's consent. Among the women already
      tested in ANC (n = 285), 97% would accept the opt-out approach. In Zimbabwe,
      where 25% of pregnant women are HIV infected, introducing the opt-out strategy
      for HIV testing may have a far-reaching public health impact on PMTCT. Issues
      regarding, stigma, quality of post-testing counseling and staffing must be
      considered, however.

PMID- 16652063
TI  - Updated estimates of healthcare utilization and costs among perinatally HIV
      infected children.
AB  - OBJECTIVES: This study examined changes in healthcare use among perinatally HIV
      infected children and developed new estimates of expected lifetime treatment
      costs. METHODS: The study analyzed longitudinal medical record data from the
      Pediatric Spectrum of Disease study on perinatally HIV-infected children enrolled
      in 6 US sites during 1995 and 2001 for enrollee characteristics including
      healthcare utilization. For the year 2001, costs were assigned to
      hospitalization, HIV-related drug usage, and laboratory testing. To estimate
      lifetime treatment costs based on those categories, median survival times of 9,
      15, and 25 years were assumed and average annual healthcare utilization costs
      were applied to each year of survival. RESULTS: From 1995 to 2001,
      hospitalization rates fell from 0.67 per child-year to 0.23 per child-year (P <
      0.05). In 2001, the average cost of healthcare utilization per child was $12,663,
      including $2164 for hospitalization, $9505 for HIV-related drugs, and $994 for
      laboratory tests. The discounted lifetime treatment cost, based on those 3 cost
      categories, was $113,476 for 9 years of survival, $151,849 for 15 years, and
      $228,155 for 25 years. CONCLUSIONS: Hospitalizations among perinatally HIV
      infected children decreased significantly from 1995 to 2001. Compared with
      previously published estimates, lifetime treatment costs for children perinatally
      infected with HIV have remained relatively stable. However, as years of survival
      increase for this population, lifetime costs also are likely to increase.

PMID- 16652064
TI  - Incidence of and risk factors for genital human papillomavirus infection in women
      drug users.
AB  - A total of 230 women drug users were prospectively studied. At 6-month intervals,
      interviews, HIV testing, and cervicovaginal lavage sampling for human
      papillomavirus (HPV) were performed. HPV was detected and typed using a MY09/MY11
      polymerase chain reaction system. 230 women without high-risk HPV (types 16, 18,
      26, 31, 33, 35, 39, 45, 51, 52, 56, 58. 59, 68, 73 and 82), with or without non
      high risk HPV types at baseline, were included in analyses. Incidence rates of
      and factors associated with HPV infections of all types and high-risk types
      (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) were
      analyzed. Baseline median age was 40 years (range 24-65); 62% of women were
      Hispanic, 20% black, and 16% white; 54 (24%) were HIV seropositive; 172 (75%)
      were without detectable HPV; 58 (25%) had only low-risk or untypeable HPV. The
      incidence rates for any and for high-risk type HPV infection were 9.5/100 and
      4.8/100 person-years, respectively. HIV-positive women had a significantly
      increased hazard rate for any HPV (HRadj: 3.4; 95% CI: 1.4 to 8.0) and for high
      risk HPV (HRadj 3.0; 95% CI: 1.4 to 6.6), adjusted for race, sexual behaviors,
      condom use, and history of other sexually transmitted infections. HIV infection
      was independently associated with a substantial and significantly increased risk
      for any and for high-risk genital HPV infection and was the most important risk
      factor found.

PMID- 16652065
TI  - Validity of self-reported antiretroviral therapy use among injection drug users.

PMID- 16652066
TI  - Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral
      suppression.

PMID- 16652067
TI  - Bacterial disease in HIV-infected patients: the blind spot of highly active
      antiretroviral therapy?

PMID- 16652068
TI  - In utero nucleoside reverse transcriptase inhibitor exposure and cancer in HIV
      uninfected children: an update from the pediatric AIDS clinical trials group 219
      and 219C cohorts.

PMID- 16652069
TI  - Internet-based screening for Chlamydia trachomatis to reach non-clinic
      populations with mailed self-administered vaginal swabs.
AB  - BACKGROUND: Testing for Chlamydia trachomatis by nucleic acid amplification tests
      (NAATs) using self-collected vaginal swabs (VS) is acceptable and accurate. The
      objectives were to implement an educational Internet-based program for women to
      facilitate home screening, to determine whether women would request and use self
      collected VS kits, to determine associated risk factors for infection, and to
      determine satisfaction with the process. METHODS: The website,
      www.iwantthekit.org, was designed to encourage women > or =14 years to obtain
      home-sampling kits. Kits could be obtained in the community, requested by
      Internet/e-mail, or telephone. Users mailed the self-collected VS to the
      laboratory. Swabs were tested by 3 NAAT assays. Respondents called for results.
      RESULTS: Forty-one of 400 (10.3%) women were chlamydia positive; 95.1% were
      treated. Questionnaires indicated 89.5% preferred self-collection, 93.5% rated
      collection easy/very easy, and 86.3% would use the Internet program again. Black
      race and age <25 years were associated independently with being chlamydia
      positive, while use of birth control and non-consensual sex were protective.
      Thirty-six of 41 (87.8%) positive samples were positive by all 3 NAATs, 5/41
      (12.2%) were positive by only 2 NAATs, and none were positive by only 1 NAAT. The
      Internet/e-mail request method was better than the community pick-up approach
      because 97.2% of kit requests were e-mailed and 87.5% of kits returned for
      testing were e-mail requested. CONCLUSIONS: Women will use the Internet to
      request and use home-sampling kits for chlamydia. NAAT testing performed well on
      dry-transported VS. High prevalence was detected and questionnaires indicated
      high-risk sexual behavior.

PMID- 16652070
TI  - From trial intervention to scale-up: costs of an adolescent sexual health program
      in Mwanza, Tanzania.
AB  - OBJECTIVE: To estimate annual costs of a multifaceted adolescent sexual health
      intervention in Mwanza, Tanzania, by input (capital and recurrent), component (in
      school, community activities, youth-friendly health services, condom
      distribution), and phase (development, startup, trial implementation, scale-up).
      STUDY DESIGN: Financial and economic providers' costs and intervention outputs
      were collected to estimate annual total and unit costs (1999-2001). The
      incremental financial budget projects funding requirements for scale-up within an
      integrated model. RESULTS: The 3-year economic costs of trial implementation were
      US dollars 879,032, of which approximately 70% were for the school-based
      component. Costs of initial development and startup were relatively substantial (
      approximately 21% of total costs); however, annual costs per school child dropped
      from US dollars 16 in 1999 to US dollars 10 in 2001. The incremental scale-up
      cost is approximately 1/5 of ward trial implementation running costs.
      CONCLUSIONS: Annual costs can reduce by almost 40% as project implementation
      matures. When scaled up, only an additional US dollars 1.54 is needed per pupil
      per year to continue the intervention.

PMID- 16652071
TI  - Effect of gabapentin on the sensation and impact of tinnitus.
AB  - OBJECTIVES/HYPOTHESIS: This study evaluated the effectiveness of gabapentin in
      treating chronic tinnitus in two populations: participants with tinnitus with
      associated acoustic trauma and participants with tinnitus without associated
      acoustic trauma. The hypothesis was that gabapentin would decrease both
      subjective and objective features of tinnitus in the trauma group but would be
      less effective in the nontrauma group. STUDY DESIGN: Prospective, placebo
      controlled, single-blind clinical trial. METHODS: Pure-tone audiograms and
      personal histories were used to categorize tinnitus etiology as either secondary
      to acoustic trauma or not associated with acoustic trauma. Participants were
      restricted to those with moderate to severe tinnitus for at least 1 year. All
      participants received gabapentin in a graduated ascending-descending dose series
      extending over 20 weeks (peak dose of 2,400 mg/d). RESULTS: There was a
      significant improvement in tinnitus annoyance for the trauma group (P = .05).
      Other subjective aspects of tinnitus were not significantly affected in either
      group. Between-subject variability of therapeutic response was considerable.
      Nevertheless, in consideration of subjective loudness ratings, 4 of 19 nontrauma
      participants and 6 of 20 trauma participants showed an improvement of 20% or
      better. In consideration of psychoacoustic loudness estimates, 3 of 19 nontrauma
      and 6 of 20 trauma participants showed an improvement of 20 dB HL or greater.
      Evenly dividing each group into high and low responders revealed significant
      improvement in loudness at 1,800 and 2,400 mg/day for the trauma high-response
      subgroup (P = .007). No significant improvement was obtained for other subgroups.
      CONCLUSION: Gabapentin is effective in reducing subjective and objective aspects
      of tinnitus in some individuals, with the best therapeutic response obtained in
      individuals with associated acoustic trauma.

PMID- 16652072
TI  - Assessing and documenting general competencies in otolaryngology resident
      training programs.
AB  - OBJECTIVES: The objectives of this study were to: 1) implement web-based
      instruments for assessing and documenting the general competencies of
      otolaryngology resident education, as outlined by the Accreditation Council of
      Graduate Medical Education (ACGME); and 2) examine the benefit and validity of
      this online system for measuring educational outcomes and for identifying
      insufficiencies in the training program as they occur. METHODS: We developed an
      online assessment system for a surgical postgraduate education program and
      examined its feasibility, usability, and validity. Evaluations of behaviors,
      skills, and attitudes of 26 residents were completed online by faculty, peers,
      and nonphysician professionals during a 3-year period. Analyses included
      calculation and evaluation of total average performance scores of each resident
      by different evaluators. Evaluations were also compared with American Board of
      Otolaryngology-administered in-service examination (ISE) scores for each
      resident. Convergent validity was examined statistically by comparing ratings
      among the different evaluator types. RESULTS: Questionnaires and software were
      found to be simple to use and efficient in collecting essential information. From
      July 2002 to June 2005, 1,336 evaluation forms were available for analysis. The
      average score assigned by faculty was 4.31, significantly lower than that by
      nonphysician professionals (4.66) and residents evaluating peers (4.63) (P <
      .001), whereas scores were similar between nonphysician professionals and
      resident peers. Average scores between faculty and nonphysician groups showed
      correlation in constructs of communication and relationship with patients, but
      not in those of professionalism and documentation. Correlation was observed in
      respect for patients but not in medical knowledge between faculty and resident
      peer groups. Resident ISE scores improved in the third year of the study and
      demonstrated high correlation with faculty perceptions of medical knowledge (r =
      0.65, P = .007). CONCLUSIONS: Compliance for completion of forms was 97%. The
      system facilitated the educational management of our training program along
      multiple dimensions. The small perceptual differences among a highly selected
      group of residents have made the unambiguous validation of the system
      challenging. The instruments and approach warrant further study. Improvements are
      likely best achieved in broad consultation among other otolaryngology programs.

PMID- 16652073
TI  - Squamous cell carcinoma of the sinonasal cavity arising as a second primary in
      individuals with head and neck cancer.
AB  - OBJECTIVES/HYPOTHESIS: Second primary tumors occur frequently in patients with
      head and neck carcinoma. This may be caused by generalized exposure to
      carcinogens resulting in "field cancerization" or to the individuals' generalized
      susceptibility to cancer. The paranasal sinuses are not commonly included in the
      sites considered at risk for this process. We therefore sought to assess the
      overall risk of contracting a primary cancer in this region after having a tumor
      elsewhere in the upper aerodigestive tract. STUDY DESIGN: Retrospective. METHODS:
      Two thousand four hundred seventy-five patients with squamous cell carcinoma of
      the upper aerodigestive tract were analyzed using a tumor registry at a tertiary
      care institution. RESULTS: Five (0.2%) patients were identified as having a
      second primary in the sinonasal tract. The average interval between the index and
      second primary tumors was 28.4 (range 8-60) months. All five patients presented
      with symptoms typical of sinus inflammatory disease and had advanced sinus
      lesions at the time of diagnosis. These findings are typical of those with
      sinonasal carcinoma in that they present with nonspecific signs and symptoms and
      were diagnosed with locally advanced disease despite being in a surveillance
      program for their index cancer. CONCLUSIONS: Although uncommon, the data reported
      here support inclusion of the sinonasal tract in these surveillance programs.
      This could result in earlier detection and greater opportunity for curative
      intervention.

PMID- 16652074
TI  - Tissue-engineered calcium alginate patches in the repair of chronic chinchilla
      tympanic membrane perforations.
AB  - OBJECTIVE: Chronic tympanic membrane perforations are a common problem in the
      United States. A high number of these cases results from placement of pressure
      equalization tubes. These perforations may initially be treated with paper patch
      techniques and although safe and well tolerated, the procedure demonstrates poor
      efficacy. The ideal treatment for small perforations should be rapid, minimally
      invasive, and efficacious. Calcium alginate-based tissue engineered tympanic
      membrane patches represent an attractive option, but in vivo data are required.
      METHODS: A controlled prospective study of tympanic membrane perforation repair
      using a well-known chinchilla model of chronic tympanic membrane perforation was
      performed. Calcium alginate-based tympanic membrane patches were created using
      computer-aided design techniques. A previously described chinchilla model of
      chronic tympanic membrane perforations was used to create stable perforations
      ranging from 2 to 5 mm. Ears with chronic perforations were divided into three
      groups: control (no patch), paper patch, and calcium alginate plugs. At 10 weeks
      postimplantation, all animals were killed and inspected both grossly and
      histologically for healing. RESULTS: In the chinchilla model, the alginate grafts
      demonstrated significantly improved healing rates over both the untreated control
      group (spontaneous repair) and the paper patch group; nine of 13 healed in the
      alginate group versus two of nine healed in the paper patch group (P < .05)
      versus one of 11 healed in the control group (P < .05). CONCLUSION: Calcium
      alginate tympanic membrane perforation patches offer a significant advantage in
      the repair of chronic perforations over traditional techniques in the chinchilla
      perforation model and may offer attractive opportunities in the clinical setting.

PMID- 16652075
TI  - Utility of positron emission tomography-computed tomography in identification of
      residual nodal disease after chemoradiation for advanced head and neck cancer.
AB  - OBJECTIVES: Planned neck dissection after chemoradiation (CR) is often advocated
      in patients with head and neck squamous cell cancer (HNSCC) with advanced nodal
      disease who demonstrate a clinical complete response to CR because identification
      of residual occult nodal disease is difficult. We sought to investigate the
      utility of positron emission tomography-computed tomography (PET-CT) in
      identifying patients with occult nodal disease after CR. STUDY DESIGN:
      Nonrandomized retrospective cohort analysis. MATERIALS AND METHODS: The medical
      records of all patients treated with primary CR for advanced HNSCC with N2 or N3
      disease from December 2003 to June 2005 were reviewed. Patients with a clinical
      complete response were eligible for inclusion if PET-CT performed at 8 to 10
      weeks after CR showed no evidence of distant disease and they were treated with a
      planned neck dissection. RESULTS: Seventeen patients met study criteria. PET-CT
      was positive for residual nodal disease in 11 (64.7%) patients, with a
      standardized uptake value (SUV) range of 1.7 to 3.8. Pathologic examination
      revealed residual viable carcinoma in five (29.4%) patients, with tumor size
      ranging from 2.0 to 9.5 mm. Carcinoma was present in 2 of 11 (18.2%) patients
      with positive PET-CT scans and 3 of 6 (50%) patients with negative PET-CT scans.
      The sensitivity and specificity of PET-CT in predicting occult nodal disease was
      40% and 25%, respectively. There was no correlation between PET-CT findings and
      histologic findings (P = .26) or between SUV and size of viable tumor (P = .67).
      CONCLUSIONS: A significant proportion of HNSCC patients with advanced neck
      disease harbor residual occult metastases after CR. PET-CT is not sufficiently
      specific or sensitive to reliably predict the need for posttreatment neck
      dissection.

PMID- 16652076
TI  - Three-dimensional reconstruction and modeling of middle ear biomechanics by high
      resolution computed tomography and finite element analysis.
AB  - OBJECTIVE: To present a systematic and practical approach that uses high
      resolution computed tomography to derive models of the middle ear for finite
      element analysis. STUDY DESIGN: This prospective study included 31 subjects with
      normal hearing and no previous otologic disorders. Temporal bone images obtained
      from 15 right ears and 16 left ears were used for evaluation and reconstruction.
      METHODS: High-resolution computed tomography of temporal bone was performed using
      simultaneous acquisition of 16 sections with a collimated slice thickness of
      0.625 mm. All images were transferred to an Amira visualization system for three
      dimensional reconstruction. The created three-dimensional model was translated
      into two commercial modeling packages, Patran and ANSYS, for finite element
      analysis. RESULT: The characteristic dimensions of the model were measured and
      compared with previously published histologic section data. This result confirms
      that the geometric model created by the proposed method is accurate except that
      the tympanic membrane is thicker than when measured by the histologic section
      method. No obvious difference in the geometrical dimension between right and left
      ossicles was found (P > .05). The three-dimensional model created by finite
      element method and predicted umbo and stapes displacements are close to the
      bounds of the experimental curves of Nishihara's, Huber's, Gan's, and Sun's data
      across the frequency range of 100 to 8000 Hz. CONCLUSION: The model includes a
      description of the geometry of the middle ear components and dynamic equations of
      vibration. The proposed method is quick, practical, low-cost, and, most
      importantly, noninvasive as compared with histologic section methods.

PMID- 16652077
TI  - Audiologic performance and benefit of cochlear implantation in Usher syndrome
      type I.
AB  - OBJECTIVE: The objective of this retrospective study was to evaluate the benefit
      and performance of cochlear implantation in patients with Usher syndrome type 1
      (USH1). METHODS: Fourteen patients with a clinical diagnosis of USH1 were
      included. Mutation analysis of USH1 genes was performed in all of them. All
      patients filled in the G(C)BI questionnaire, which measures the benefit of
      implantation. In addition, equivalent hearing level scores (EHL) were calculated
      to measure performance. Correlations between the mentioned parameters were
      studied. RESULTS: One or two pathogenic mutations were identified in seven of the
      14 examined patients. Similar to previous studies, it was demonstrated that
      implantation at an earlier age results in better performance than implantation at
      higher age. Cochlear implantation performed within the first 2 decades of life
      was beneficial to 13 of 14 (93%) of the patients with USH1. Finally, the EHL
      score and the G(C)BI score showed a significant correlation; the benefit of
      implantation increases with a decreasing EHL score. CONCLUSIONS: Cochlear
      implantation in patients with USH1 improves the audiologic performance when
      patients are implanted at an earlier age and is beneficial according to the
      G(C)BI when performed within the first 2 decades of life.

PMID- 16652078
TI  - Quality of life and cochlear implantation in Usher syndrome type I.
AB  - OBJECTIVES: The objectives of this descriptive, retrospective study were to
      evaluate quality of life, hearing, and vision in patients with Usher syndrome
      type I with and without cochlear implant. METHODS: Quality of life (QoL) of 14
      patients with Usher type I (USH1) with a cochlear implant (CI) (seven adults,
      seven children) was compared with those of 14 patients with USH1 without a CI (12
      adults, two children) by means of three questionnaires: NCIQ, SF12, and the Usher
      Lifestyle Survey. Additional information on hearing level was obtained by the
      equivalent hearing loss (EHL) principle and on the visual deterioration by the
      functional vision score (FVS). RESULTS: A significant benefit of CI was seen in
      the hearing-specific questionnaire NCIQ. This difference could not be detected in
      the generic SF12 survey. The Usher Lifestyle Survey indicated that patients with
      USH1 with a CI tend to be able to live an independent life more easily than the
      profoundly deaf unimplanted patients with USH1. EHL and FVS scores varied in both
      groups. CONCLUSIONS: Overall QoL can be enhanced by CI in patients with USH1,
      although effects are mostly seen in hearing-related QoL items.

PMID- 16652079
TI  - Comparative study on the long-term effectiveness between coblation- and
      microdebrider-assisted partial turbinoplasty.
AB  - OBJECTIVES: Various surgical methods have been tried to relieve the symptoms of
      nasal obstruction in patients with inferior turbinate hypertrophy. Recently,
      coblation that uses the radiofrequency and microdebrider is being increasingly
      used in turbinate surgery. The aim of this study was to compare the long-term
      postoperative outcome between the coblation- and microdebrider-assisted partial
      turbinoplasty. METHODS: We selected 60 patients for this prospective study who
      had nasal obstruction and hypertrophied turbinate mucosa that was refractory to
      medical treatment. Thirty patients were treated with coblation (group 1) and 30
      patients were treated with microdebrider (group 2). Postoperative changes in
      degree of nasal obstruction were evaluated prospectively at 3, 6, and 12 months
      after the procedure. A cross-sectional area of second notch and volume of nasal
      cavity were compared at 12 months after operation. Operation time, duration of
      crust formation, postnasal drip, and postoperative bleeding were also compared.
      RESULTS: Nasal obstruction was improved significantly in both groups at 3, 6, and
      12 months after the procedure. However, when compared between two groups, symptom
      improvement was statistically significant in group 2 at 12 months after surgery.
      Acoustic rhinometry performed at 12 months demonstrated a significant increase of
      cross-sectional area of second notch and volume of nasal cavity in group 2 in
      comparison with group 1. There were no significant differences in degree of
      postnasal drip, operation time, or duration of crust formation between the two
      groups. CONCLUSION: This study suggests that microdebrider-assisted partial
      turbinoplasty is more effective and satisfactory in long-term relief of nasal
      obstruction and reduction in mucosal volume of anterior head of inferior
      turbinate.

PMID- 16652080
TI  - Genome-wide profiling of oral squamous cell carcinoma by array-based comparative
      genomic hybridization.
AB  - OBJECTIVES: Array-based comparative genomic hybridization (aCGH) was used to
      develop a genome-wide molecular profile of oral squamous cell carcinoma (OSCC).
      Copy number alterations (CNAs) were identified by chromosomal region, mapped to
      specific genes, and compared with several previously documented CNAs associated
      with head and neck squamous cell carcinoma (HNSCC). The status of 512 commonly
      altered cancer genes was assessed and evaluated as potential correlates of tumor
      behavior. METHODS: Tumor tissue DNA was isolated for aCGH from 21 prospectively
      collected fresh-frozen OSCC specimens. aCGH was performed at 0.9-Mb resolution to
      identify distinct regions of genomic alteration and their associated genes.
      Cancer genes commonly altered were then correlated with clinicopathologic tumor
      data. RESULTS: Genomic regions most frequently amplified (>35%) were located on
      3q, 5p, 8q, 9q, and 20q, although regions most frequently deleted (>40%) involved
      chromosomes 3p, 8p, 13q, and 18q. Minimal regions of CNA identified, by aCGH
      narrowed larger, previously documented CNAs associated with HNSCC to
      significantly smaller regions, yielding shorter lists of candidate genes. Cancer
      related genes altered in greater than 25% OSCC samples were identified (22
      amplified, 17 deleted). Several genes associated with the Fanconi anemia DNA
      damage response pathway were frequently altered, including BRCA1, BRCA2, FANCD2,
      and FANCG. Other cancer-related genes linked to hereditary cancer syndromes
      include VHL, MLH1, XPC, and RB1. CONCLUSIONS: Genome-wide aCGH can be used to
      detect and map CNAs in OSCC tissue specimens with high resolution. These data
      implicate several candidate genes and gene pathways in the tumorigenesis of
      sporadic OSCC.

PMID- 16652081
TI  - Surgical removal of jugular paragangliomas after stenting of the intratemporal
      internal carotid artery: a preliminary report.
AB  - OBJECTIVE: Jugular paragangliomas with extensive involvement of the internal
      carotid artery (ICA) represent a true challenge for surgeons, especially in the
      presence of inadequate collateral circulation through the circle of Willis. The
      aim of our study is to present a preliminary report of our experience with the
      surgical removal of three such cases using the stenting of the ICA as the method
      of choice for protecting and preserving the integrity of the artery. METHODS:
      This retrospective study was conducted at Gruppo Otologico, a private referral
      center for neurotology and skull base surgery. The subjects of our study are
      three cases of jugular paragangliomas with extensive involvement of the ICA and
      inadequate collateral circulation. These cases are the first three cases operated
      at our center after stenting of the intratemporal portion of the ICA. RESULTS:
      Complete surgical removal of the tumor, including the part involving the ICA, was
      achieved in all cases. Over a follow-up period of 22 to 30 months, no
      complications occurred and the patency of the stented arteries was preserved.
      CONCLUSION: Although more follow-up is still needed before establishing the exact
      long-term outcome of stenting the intratemporal ICA, our preliminary report shows
      that the stent has facilitated the complete surgical removal of the tumor,
      preserving the integrity of the ICA.

PMID- 16652082
TI  - Intratympanic dexamethasone injection for refractory sudden sensorineural hearing
      loss.
AB  - OBJECTIVE: This case-control study aimed to analyze the effect of intratympanic
      dexamethasone injection (ITDI) as a treatment option for patients with sudden
      sensorineural hearing loss (SSNHL) who were refractory to classic oral steroid
      treatment. METHODS: Sixty-six patients with SSNHL, who were refractory to a
      course of oral steroid therapy, were included in this study. We prospectively
      treated consecutive 33 patients (34 ears) with ITDI from August 2002 to January
      2004. We then retrospectively collected data from age- and sex-matched previous
      patients who did not take any more treatments after the initial regimen between
      March 2000 and July 2002. ITDI was performed in the supine position on four
      separate occasions over the course of 2 weeks. Hearing was assessed immediately
      before every injection and at 1 week after therapy. Hearing improvement was
      defined as more than 10 dB in pure-tone average (PTA). RESULTS: Hearing
      improvement was observed in 13 (39.4%) of 33 patients who underwent ITDI and in
      two (6.1%) of 33 patients in the control group. Five of 13 represented hearing
      improvement over than 20 dB in PTA, and 11 of 20 patients, who showed no
      improvement in PTA by ITDI, showed improvement over 10 dB in some frequencies.
      There were no definite prognostic factors between the patients who responded to
      ITDI and those who did not. CONCLUSION: ITDI may be a simple and effective
      therapy for patients with refractory SSNHL.

PMID- 16652083
TI  - Direct measurement of subglottic air pressure while swallowing.
AB  - OBJECTIVE: The subglottic pressure theory for swallowing asserts that laryngeal
      mechanoreceptors have a role in the regulation of swallowing function. The
      primary purpose of this study was to determine if subglottic air pressure is
      generated during swallowing in a healthy, nontracheostomized person. METHODS:
      This pilot investigation used a prospective, repeated-measures design in a single
      subject. Direct measurement of subglottic air pressure was obtained through
      percutaneous puncture of the cricothyroid membrane. Swallows were timed with four
      randomly assigned lung volumes: total lung capacity, tidal volume, functional
      residual capacity (FRC), and residual volume. RESULTS: Lung volumes above FRC
      generated positive subglottic pressure during the swallow, whereas lung volumes
      below FRC generated consistently negative subglottic pressures. The degree and
      polarity of the pressure was directly related to lung volume at the time of the
      swallow. CONCLUSION: These findings illustrate that during normal swallowing,
      positive subglottic air pressure is likely present. Previously, subglottic air
      pressure during swallowing had been measured in tracheostomy patients only.

PMID- 16652084
TI  - Molecular basis of posttransplant squamous cell carcinoma: the potential role of
      cyclosporine a in carcinogenesis.
AB  - Cyclosporine (CSA) is a widely used immunosuppressive agent, predominantly for
      transplant patients. It is well recognized that transplant patients are prone to
      develop squamous carcinoma of the skin and mucosa, and this high incidence of
      squamous carcinoma in the transplant population cannot be explained by
      immunosuppression alone. We hypothesize that CSA may play a significant role in
      the transformation of normal epidermal squamous cells to carcinoma. CSA is a
      specific ligand for calcineurin, a ubiquitously expressed cellular
      serine/threonine phosphatase, that plays important roles in the immune system and
      cardiac muscles. Using global gene-profiling methods, we studied the short-time
      CSA effect on the squamous cell line (SCC-015) using Affymetrix human gene chips
      (Human U133, 2.0 plus chip). Multiple groups of genes were identified to be
      responsive to CSA treatment, including many genes of unknown functions. We then
      used reverse transcriptase-polymerase chain reaction and immunoblot analyses to
      selectively confirm the results from the chips analyses with emphasis on the
      regulatory molecules important for cellular functions of apoptosis, DNA damage
      repair, and cellular transformation. This global gene-profiling study indicated
      that CSA not only functions as an immunosuppressant on the immune system, but
      also activates/inhibits a wide array of genes important for cell-cycle
      regulation, apoptosis, and oncogene/tumor-suppressor activation. These functions
      of CSA on skin and mucosa systems at the molecular level are likely important in
      the pathogenesis of squamous carcinoma in transplant patients.

PMID- 16652085
TI  - A short course of oral prednisone followed by intranasal budesonide is an
      effective treatment of severe nasal polyps.
AB  - BACKGROUND: Nasal polyposis is an inflammatory disease of unknown etiology. This
      study aimed to evaluate the effect of a short course of oral prednisone followed
      by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed
      tomography scan. METHODS: Eighty-four patients with severe nasal polyps were
      included. After a steroid washout period, patients were randomized into two
      groups: group A (n = 63) received oral prednisone for 2 weeks and group B (n =
      21) did not receive any steroid treatment. Patients from group A received
      intranasal budesonide for 12 weeks. RESULTS: Atopy was positive in 36.8% of
      patients. Blood eosinophilia was higher in asthmatic (7.2 +/- 0.7%, P < .05) than
      in nonasthmatic (3.0 +/- 0.4%) patients. Asthmatic patients showed higher scores
      on nasal obstruction and loss of smell than nonasthmatics. Oral steroids caused a
      significant improvement in all nasal symptoms and improved polyp size (2.1 +/-
      0.1, P < .05) and nasal flow (560 +/- 35 cm/s, P < .05) compared with nontreated
      patients (2.8 +/- 0.1 and 270 +/- 34 cm/s, respectively). Intranasal budesonide
      maintained the improvement on nasal symptoms, polyp size, and nasal flow. Steroid
      treatment reduced the computed tomography scan score (15.4 +/- 1, P < .05)
      compared with before treatment (18.2 +/- 0.8). CONCLUSION: A short course of oral
      steroids improved all nasal symptoms, polyp size, and nasal flow, whereas
      intranasal steroid maintain this effect.

PMID- 16652086
TI  - Vestibular evoked myogenic potential (VEMP) in patients with Meniere's disease
      with drop attacks.
AB  - OBJECTIVE: In this retrospective study, we tested the hypothesis that vestibular
      evoked myogenic potential (VEMP) thresholds are more often elevated or absent in
      patients with Meniere's disease experiencing Tumarkin drop attacks than in other
      patients with Meniere's disease. METHODS: Subjects included normal subjects (n =
      14) and patients with unilateral Meniere's disease by AAO-HNS (1995) diagnostic
      criteria with (n = 12) and without (n = 82) Tumarkin drop attacks at a large
      specialty hospital otology service. VEMP threshold testing was conducted using
      250, 500, and 1,000 Hz tone burst stimuli. RESULTS: VEMP responses were present
      in at all frequencies in both ears of all normal subjects. In unaffected ears of
      patients with unilateral Meniere's disease, VEMPs were undetectable in 13% of
      measurements attempted. This number rose to 18% in affected ears of patients with
      unilateral Meniere's disease and to 41% in Meniere ears with Tumarkin drop
      attacks. Frequency tuning of the VEMP response in normal subjects showed lowest
      thresholds at 500 Hz. In Meniere ears, the tuning was altered such that the 500
      Hz thresholds were higher than the 1,000-Hz thresholds. There was a gradient of
      threshold elevation and altered tuning that corresponded to the gradient of
      worsening disease. CONCLUSION: Our findings support the hypothesis that Tumarkin
      drop attacks arise from advanced disease involving the saccule and that VEMP may
      be a clinically valuable metric of disease severity or progression in patients
      with Meniere's disease.

PMID- 16652087
TI  - Soft-tissue sarcomas of the head and neck: a retrospective analysis of the
      Alberta experience 1974 to 1999.
AB  - BACKGROUND: Soft-tissue sarcomas (STS) of the head and neck constitute a
      heterogeneous group of rare malignant tumors occurring in an uncommon site. The
      most common subtypes of STS in the head and neck are malignant fibrous
      histiocytoma, dermatofibrosarcoma protuberans, and fibrosarcoma. Evidence based
      subtype-specific treatment decisions are often not possible. METHODS: The medical
      records of 110 patients diagnosed with head and neck sarcomas were reviewed. All
      were treated at one of the two major Cancer Centers in Alberta, Canada, between
      1974 and 1999. Potential prognostic factors including age, sex, tumor size,
      histology, grade, tumor location (superficial or deep), and use of adjuvant
      treatment were evaluated. Cox proportional hazards models were developed to study
      the impact of these covariates on survival. RESULTS: The median duration of
      follow-up was 61.5 months. Five year overall, disease specific, and relapse free
      survival were 65.8%, 83.4%, and 74.2%, respectively. With use of a Cox
      proportional-hazards model, tumor stage and grade were important prognostic
      factors affecting survival. CONCLUSIONS: Tumor size and grade were important
      prognostic factors affecting survival. Tumor location in relation to the
      superficial fascia (depth) was the best predictor of outcome. The overall and
      disease-free survival in this patient group was excellent. However, this likely
      caused by the high proportion of patients with low-grade tumors in our study.

PMID- 16652088
TI  - Partial cricotracheal resection for successful reversal of laryngotracheal
      separation in patients with chronic aspiration.
AB  - OBJECTIVE: To present our experience with successful reversal of laryngotracheal
      separation in patients with chronic aspiration, to discuss our surgical
      technique, and to review the literature. STUDY DESIGN: Retrospective case review.
      METHODS: The medical records of two patients who underwent a successful reversal
      of laryngotracheal reversal after separation were reviewed. The two patients were
      evaluated clinically with videostroboscopy and videofluoroscopy. RESULTS: Both
      patients presented with intractable aspiration despite protective tracheostomy
      because of impairment of lower cranial nerve function. After laryngotracheal
      separation, swallowing rehabilitation was safely possible, and neurologic
      improvement allowed reversal of the separation procedure. For reversal, we
      present the use of a partial cricotracheal resection with tracheocricothyropexia
      similar to the technique used for subglottic stenosis. Both patients were
      successfully reversed. Satisfactory voice and swallowing function 7 and 10 years
      after reversal, respectively, could be assessed through our evaluation. Review of
      the literature revealed a total of 13 cases of successful reversal after
      laryngotracheal separation. Technical details of surgery and functional results
      are rarely reported.

PMID- 16652089
TI  - Merkel cell carcinoma: does tumor size or depth of invasion correlate with
      recurrence, metastasis, or patient survival?
AB  - OBJECTIVE: The objective of this retrospective study and literature review was to
      compare the clinical and histologic criteria including tumor size and depth of
      invasion with outcomes in patients with Merkel cell carcinoma. METHODS: The state
      cancer registry provided patients (n = 46) diagnosed with Merkel cell carcinoma
      from 1992 through 2002. Pathology slides were reviewed by the author for tumor
      size, depth of invasion, Clark level, and margin status. Further clinical
      information and survival data were gathered from patient records. Statistical
      analysis was performed using t tests and Kaplan-Meier survival curves. Patients
      were excluded from specific analysis based on misdiagnosis, unavailability of
      pathology slides, absent medical records, or those lost to follow up. RESULTS:
      Disease-free survival rates were 52%, 39%, and 9% at 1, 2, and 5 years,
      respectively. The average disease-free interval was 18.4 months (range, 1-80
      months). No correlation was found between tumor size (P = .49), depth (P = .41),
      or Clark level (P = .82) to overall survival. A trend was found comparing tumor
      size or depth of invasion with local recurrence (P = .07) but with no correlation
      to regional recurrence (P = .93 and P = .60) or distant metastasis (P = .16 and P
      = .24). Overall recurrence was found in 60.7% of patients with local recurrence
      occurring in 18.1%, regional recurrence 40.9%, and distant recurrence 47.8%.
      Comparing patients with positive versus negative margins at initial excision,
      local recurrence was found in 33.3% versus 9.09% (P = .19), regional recurrence
      66.6% versus 27.2% (P = .08), and distant metastasis 66.6% versus 45.4% (P =
      .36), respectively. CONCLUSIONS: No correlation was found between tumor size or
      depth of invasion to patient survival or metastasis. However, there was a trend
      toward increased local and regional recurrence rates when comparing size and
      depth and in specimens with positive tumor margins. These outcomes are consistent
      with those reported in recent literature and further characterize the
      unpredictable nature of this disease. An aggressive approach should be taken,
      including wide local excision with negative tumor margins and lymph node
      dissection; however, larger multistate reviews are needed for additional support.

PMID- 16652090
TI  - SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient
      with branchio-oto syndrome.
AB  - OBJECTIVES: : The objectives of this study were to identify SIX1 gene mutations
      in a patient with branchio-oto syndrome (BO) and to clarify the relationship
      between SIX1 mutation and enlargement of the vestibular aqueduct (EVA). METHODS:
      : A genetic study and retrospective chart review for a patient in whom EYA1
      mutation had already been excluded was conducted. We studied a Japanese patient
      who had autosomal-dominant mixed hearing loss, a unilateral ear pit and
      unilateral EVA, and who was previously diagnosed as having BO. We searched for
      SIX1 and SLC26A4 mutations using polymerase chain reaction and direct gene
      sequencing. RESULTS: : The patient carried a heterozygous A-->G mutation at
      nucleotide 386 within exon 1 of SIX1 that resulted in substitution of a cysteine
      for a tyrosine at codon 129 (Y129C) of the gene product. Y129C is a previously
      identified SIX1 mutation and was not detected in any of our 164 control
      chromosomes. No SLC26A4 mutations were identified. CONCLUSION: : Y129C mutation
      in SIX1 may cause EVA as well as BO.

PMID- 16652091
TI  - Human cochleae with three turns: an unreported malformation.
AB  - OBJECTIVE: The objective of this histologic study of archival temporal bone
      sections was to describe the morphology of human cochleae found with three turns,
      a previously unreported anomaly, found in three pairs of temporal bones. METHODS:
      The authors conducted histopathologic processing and measurement of basilar
      membrane length. Basilar membrane length was compared with that found in six
      normal control bones. RESULTS: Cochleae with three complete turns, rather than
      the usual two and a half turns, are described for the first time. All had longer
      than normal basilar membranes, with a mean length of 40.6 mm compared with a mean
      of 33.8 mm in the normal bones. CONCLUSIONS: Human cochleae with three turns
      exist as an unreported anomaly. This is a new category of anomaly, not likely
      based on interruption of development.

PMID- 16652092
TI  - Endoscopic sentinel lymph node biopsy in a porcine model.
AB  - OBJECTIVE: The objective of this study was to investigate the feasibility of
      endoscopic sentinel lymph node biopsy in a porcine model. METHODS: One hundred
      microcuries of technetium-labeled sulfa colloid (Tc-SC) was injected into the
      right and left ventrolateral surfaces of the oral tongue of six adult Yorkshire
      pigs. A handheld gamma probe was used to locate the region of focal radioactivity
      on the neck that corresponded to the sentinel lymph node (SLN). Next, 0.25 mL of
      isosulfan blue dye was injected into the Tc-SC injection sites on the tongue.
      Endoscopic SLN dissection was then performed using a combination of balloon
      dissection and CO2 insufflation. The operative time, blood loss, and
      radioactivity of the SLN were measured for each animal. RESULTS: The SLN was
      detected transcutaneously with the gamma probe, and endoscopic SLN excision was
      successful. Endoscopic visualization and an endoscopic gamma probe confirmed the
      presence of both isosulfan blue dye and radiopositivity in the SLN in each pig.
      The procedure lasted 22 to 61 minutes (median duration, 35 minutes). There was no
      measurable blood loss in any of the animals. Mean radioactivity measured 14,466
      counts/second per lymph node. CONCLUSIONS: Endoscopic SLN biopsy for oral tongue
      lesions is feasible and warrants further study.

PMID- 16652093
TI  - FDG-PET in the clinically negative neck in oral squamous cell carcinoma.
AB  - OBJECTIVE: With improved diagnostic imaging techniques, it remains difficult to
      reduce occult metastatic disease in oral squamous cell carcinoma (SCC) to less
      than 20%. Therefore, supraomohyoid neck dissection (SOHND) still is a valuable
      staging procedure in these patients. METHODS: Patients with clinically and
      ultrasonographically staged cN0 SCC of the oral cavity underwent FDG-PET before
      SOHND. Histologic examination of neck dissection specimens was used as a "gold
      standard." RESULTS: Twenty-eight consecutive patients were included, representing
      30 necks. Occult metastatic disease was found in 30% of SOHND specimens. Average
      diameter of metastatic deposits was 4.3 mm. Sensitivity, specificity, and
      accuracy of FDG-PET was 33%, 76%, and 63%, respectively. CONCLUSIONS: In patients
      with cN0 SCC of the oral cavity, FDG-PET does not contribute to the preoperative
      workup. FDG-PET does not replace SOHND as a staging procedure.

PMID- 16652094
TI  - Everolimus (RAD) inhibits in vivo growth of murine squamous cell carcinoma (SCC
      VII).
AB  - OBJECTIVE: Everolimus (RAD) is an mTOR inhibitor closely related to rapamycin. A
      potent immunosuppressive agent, it has also shown evidence of antineoplastic
      properties. SCC VII is a spontaneously arising murine squamous cell carcinoma
      line. This study examines the effect of everolimus on SCC VII proliferation. The
      data may provide support for the use of everolimus in transplant recipients with
      a history of malignancy. METHODS: A dose efficacy study was conducted that used a
      murine model of intradermal tumor growth and pulmonary metastases. The
      development of intradermal tumors and pulmonary metastases were studied. Of 80
      total mice, 40 received intradermal injection of 1 x 10 SCC VII cells and 40
      received intravenous injection of 1 x 10 cells to establish pulmonary metastases.
      Within each group, animals were subdivided into four subgroups that received 1) 1
      mg/kg everolimus twice a day, 2) 0.5 mg/kg everolimus twice a day, 3) 7.5 mg/kg
      cyclosporine per day, and 4) no treatment. Intradermal tumors were measured three
      times per week. Animals receiving an intravenous tumor injection were killed
      after 17 days and pulmonary metastases were quantified. Medication trough levels
      were measured in all treated animals. RESULTS: Everolimus showed statistically
      significant tumor inhibition at 1.0 mg/kg twice a day and 0.5 mg/kg twice a day
      when compared with animals treated with cyclosporine and with untreated animals
      (P < .0001). Tumor inhibition was evident in both models studied (intradermal
      tumors and pulmonary metastasis generation). CONCLUSIONS: Everolimus provides
      potent tumor inhibition in animals inoculated with SCC VII cells. Inhibition of
      both local and distant spread of disease is evident. Although most
      immunosuppressives are known to potentiate neoplastic disease, this study
      supports the use of everolimus immunosuppression in the face of prior malignancy.
      This data has significant implication for laryngeal transplantation after
      laryngectomy.

PMID- 16652095
TI  - Patient-controlled comparison of flexible endoscopic evaluation of swallowing
      with sensory testing (FEESST) and videofluoroscopy.
AB  - OBJECTIVE: The objective of this study was to compare the results of
      videofluoroscopy (VFS) with flexible endoscopic evaluation of swallowing with
      sensory testing (FEESST) in dysphagia testing. METHODS: The authors conducted a
      retrospective review of data collected over a 4-year period at a tertiary care
      medical center. The FEESST and VFS results for patients receiving both
      examinations within a 2-week period were compared with respect to swallowing
      function. Comparisons were categorized as full agreement, minor disagreement that
      would not result in a significant difference in diet recommendations, and major
      disagreement that would result in a significant difference in diet
      recommendations. Kappa with quadratic weighting was calculated to evaluate the
      inter-test agreement. RESULTS: Fifty-four patients met inclusion criteria and
      were reviewed. Forty-one percent of patients were not eating by mouth at the time
      of FEESST and the mean interval between the two examinations was 5 days.
      Laryngeal examination revealed edema/erythema in 93%, impaired pharyngeal squeeze
      in 66%, decreased laryngopharyngeal sensation in 82%, and absent laryngeal
      adductor reflex in 30%. FEESST with all consistencies revealed pooling in 89%,
      penetration in 83%, and aspiration in 65% of patients. VFS revealed pooling in
      65%, penetration in 67%, and aspiration in 54% of patients. Comparison of FEESST
      and VFS revealed full agreement in 52%, minor disagreement in 13%, and major
      disagreement in 35% of patients. A weighted kappa value of 0.324 signified only
      "fair" agreement between the two tests. CONCLUSIONS: FEESST and VFS may not
      represent comparable tests of dysphagia. Further comparative studies of tests of
      swallowing function are required to determine the ideal approach to dysphagia
      testing.

PMID- 16652096
TI  - Inner ear hemorrhage in systemic lupus erythematosus.
AB  - A 33-year-old man had systemic lupus erythematosus (SLE) with anticardiolipin
      antibody. At the age of 40 years, he experienced bilateral hearing deterioration.
      The three-dimensional fluid-attenuated inversion recovery of magnetic resonance
      imaging showed high signals bilaterally in the cochlea and vestibule. He was
      diagnosed with bilateral inner ear hemorrhage on the basis of the presence of
      anticardiolipin antibody. This is the first published case of inner ear
      hemorrhage in a patient with SLE. Our findings suggest that inner ear hemorrhage
      is associated with hearing deterioration in some patients with SLE.

PMID- 16652097
TI  - Baroreflex failure: a rare complication of carotid paraganglioma surgery.
AB  - Multiple head and neck paragangliomas are a rare occurrence. We report a patient
      with removal of bilateral carotid paragangliomas who subsequently developed
      baroreflex failure 1 month after surgery. The pathology and physiology of this
      presentation is extremely interesting because it exhibits the complex homeostatic
      mechanisms involved in the maintenance of steady-state blood pressure. Although
      rare, it is important to be aware of baroreflex failure and its variable course.
      Most postsurgical cases occur within days of surgery but, as this report
      demonstrates, hypertensive urgency can occur weeks to months after surgery; and
      if not recognized early, it can lead to disastrous postoperative complications
      such as stroke and myocardial infarction.

PMID- 16652098
TI  - A rare differential diagnosis in dysphagia: wound botulism.
AB  - The incidence of wound botulism is increasing dramatically among intravenous drug
      users. Efficient intensive care and early treatment with antitoxin is essential
      to avoid lethal courses. The clinical picture of botulism is of descending,
      symmetric, flaccid paralysis. Early symptoms include cranial nerve palsies
      resulting in blurred vision and diplopia, difficulty in focusing, ptosis, facial
      weakness, dysphagia, dysphonia, and dysarthria. Because patients presenting with
      dysarthria and dysphagia will often be seen by an ear, nose and throat specialist
      initially, this rare but upcoming neurologic disease must be considered in the
      differential diagnoses.

PMID- 16652099
TI  - Need for an urgent ultrasound examination for neck lump.
AB  - Thromboembolic phenomenon is rare but serious consequence of ovarian
      hyperstimulation syndrome (OHSS) and in vitro fertilization (IVF) treatment. We
      present a case of thrombosis of the right internal jugular vein presenting as a
      neck lump to the ENT department. Ultrasonography of the neck and upper extremity
      revealed thrombosis of right internal jugular vein. The patient was started on
      low molecular weight heparin, which resulted in resolution of her clinical
      condition. Interestingly, the majority of cases after OHSS involve thrombosis of
      the upper extremities. ENT surgeons, general physicians, and infertility experts
      should consider this in the differential diagnosis of neck swellings,
      particularly after OHSS and IVF treatment, and in this case report, we emphasis
      the need for an urgent ultrasound of the neck in such patients.

PMID- 16652100
TI  - Immediate lamina papyracea reconstruction during endoscopic sinus surgery for
      surgically managed subperiosteal abscess in children.
AB  - The sinonasal area of a child's face is the keystone of facial architecture, and
      any trauma to this area may result in facial dysplasia. Animal studies have
      proven facial skeletal growth retardation following functional endoscopic sinus
      surgery. The effect of sinus surgery on facial skeletal growth in humans still
      needs to be established. Therefore, very conservative surgical resection during
      functional endoscopic sinus surgery in children is advocated. We present a
      surgical technique of immediate lamina papyracea reconstruction during endoscopic
      sinus surgery in children. We have used this technique in endoscopic surgical
      decompression of subperiosteal abscess secondary to sinusitis in children. We
      present two cases in which this technique was used in children aged 33 months and
      8 years old. The postoperative computed tomography scans showed an intact lamina
      papyracea.

PMID- 16652101
TI  - Transseptal laser resection of recurrent carcinoma confined to the nasopharynx.

PMID- 16652102
TI  - A technical improvement in sialendoscopy to enter the salivary ducts.

PMID- 16652104
TI  - Objective computerized versus subjective analysis of facial synkinesis.

PMID- 16652106
TI  - Percutaneous injection of vocal fold with synthetic dermal filler.

PMID- 16652107
TI  - Vascular defects and liver damage by the acute inactivation of the VHL gene
      during mouse embryogenesis.
AB  - Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene leads to the
      development of central nervous system hemangioblastomas, pheochromocytomas and
      renal cell carcinomas. The biological role of the VHL gene during development is
      poorly understood because of early lethality of VHL-null embryos. To overcome
      early embryo lethality observed in the conventional knockout mouse, we introduced
      a tamoxifen-inducible Cre (CreER(TM)) transgene for the stage specific
      inactivation of the VHL gene. Acute tamoxifen-induced inactivation of the VHL
      gene at E10.5 resulted in embryonic lethality between E14.5 and E15.0 with
      extensive hemorrhage and necrosis, while littermate controls showed normal
      development. Examination of the VHL-inactivated embryos between E10.5 and E14.5
      revealed dilated blood vessels, hemorrhage and necrotizing liver damage.
      Concomitant with severe hemorrhage and abnormal vasculature at E15.0, blood
      circulation in the yolk sac was impaired in the VHL-inactivated embryos, which
      may be the cause of embryo death. Placental development looked normal before
      embryo death (E14.5); however, at E16.5 following embryo death, we observed
      reduced growth of the placental labyrinthine layer. Inactivation of the VHL gene
      resulted in hypoxia-inducible factor (HIF)-1alpha stabilization and induction of
      its target genes, VEGF and CAIX, in mouse embryonic fibroblasts (MEFs). In
      addition, we observed lactate overproduction and acidification of culture media
      by the inactivation of the VHL gene. Thus, by using a novel conditional VHL
      knockout mouse model, we could show that the VHL gene plays an important role in
      the developing vasculature and liver during embryogenesis through regulation of
      HIF-1alpha and its target genes. This mouse model will be useful for the
      screening of anti-HIF or anti-VEGF drugs in vivo. Additionally, this acute VHL
      inactivation system may provide a useful tool for the in vivo study of genes that
      cause early embryonic lethality.

PMID- 16652108
TI  - Nell-1 induces acrania-like cranioskeletal deformities during mouse embryonic
      development.
AB  - We previously reported NELL-1 as a novel molecule overexpressed during premature
      cranial suture closure in patients with craniosynostosis (CS). Nell-1
      overexpression also results in premature suture closure/craniosynostosis in
      newborn transgenic mice. On a cellular level, increased levels of Nell-1 induce
      osteoblast differentiation and apoptosis. In this report, mice over-expressing
      Nell-1 were examined during embryonic development as well as shortly after birth
      for further analysis of craniofacial defects including neural tube defects
      (NTDs). The results demonstrated that overexpression of Nell-1 could induce
      acrania at relatively late gestation stage (E15.5) in mouse embryos, through
      massive apoptosis in calvarial osteoblasts and neural cells. The induced
      apoptosis was associated with an increase in Fas and Fas-L production. In
      addition, transgenic E15.5 and newborn transgenic mice with the CS phenotype
      displayed distortion of the chondrocranium associated with premature hypertrophy
      and increased apoptosis of chondrocytes. These findings were also verified in
      vitro with primary chondrocytes transduced with AdNell-1. In conclusion, Nell-1
      overexpression can induce craniofacial anomalies associated with neural tube
      defects during embryonic development and may involve mechanisms of massive
      apoptosis associated with the Fas/Fas-L signaling pathway. NELL-1: used when
      describing the human gene; NELL-1: used when describing the human protein; Nell
      1: used when describing the rodent gene; Nell-1: used when describing the rodent
      protein.

PMID- 16652109
TI  - Derivation of male germ cells from bone marrow stem cells.
AB  - Recent studies have demonstrated that somatic stem cells have a more flexible
      potential than expected, whether put into tissue or cultured under different
      conditions. Bone marrow (BM)-derived stem cells can transdifferentiate into
      multilineage cells, such as muscle of mesoderm, lung and liver of endoderm, and
      brain and skin of ectoderm origin. Here we show that BM stem cells are able to
      transdifferentiate into male germ cells. For derivation of male germ cells from
      adult BM stem (BMS) cells, we used the Stra8-enhanced green fluoresence protein
      (EGFP) transgenic mouse line expressing EGFP specifically in male germ cells. BMS
      cell-derived germ cells expressed the known molecular markers of primordial germ
      cells, such as fragilis, stella, Rnf17, Mvh and Oct4; as well as molecular
      markers of spermatogonial stem cells and spermatogonia including Rbm, c-Kit,
      Tex18, Stra8, Piwil2, Dazl, Hsp90alpha, beta1- and alpha6-integrins. Our ability
      to derive male germ cells from BMS cells reveals novel aspects of germ cell
      development and opens the possibilities for use of these cells in reproductive
      medicine.

PMID- 16652111
TI  - Pushing research to the bottom line.

PMID- 16652110
TI  - The oligopeptide transporter hPepT1: gateway to the innate immune response.
AB  - Bacterial products that are normally present in the lumen of the colon, such as N
      formylated peptides and muramyl-dipeptide, are important for inducing the
      development of mucosal inflammation. The intestinal dipeptide transporter,
      hPepT1, which is expressed in inflamed but not in noninflamed colonic epithelial
      cells, mediates the transport of these bacterial products into the cytosol of
      colonic epithelial cells. The small bacterial peptides subsequently induce an
      inflammatory response, including the induction of MHC class I molecules
      expression and cytokines secretion, via the activation of nucleotide-binding site
      and leucine-rich repeat (NBS-LRR) proteins, for example NOD2, and activation of
      NF-kappaB. Subsequent secretion of chemoattractants by colonic epithelial cells
      induces the movement of neutrophils through the underlying matrix, as well as
      across the epithelium. These bacterial products can also reach the lamina propria
      through the paracellular pathway and across the basolateral membrane of
      epithelial cells. As a consequence, small formylated peptides can interact
      directly with immune cells through specific membrane receptors. Since immune
      cells, including macrophages, also express hPepT1, they can transport small
      bacterial peptides into the cytosol where these may interact with the NBS-LRR
      family of intracellular receptors. As in intestinal epithelial cells, the
      presence of these small bacterial peptides in immune cells may trigger immune
      response activation.

PMID- 16652112
TI  - The industrial research lab: a relic of the past?

PMID- 16652113
TI  - Full-speed ahead at Bell Laboratories?

PMID- 16652115
TI  - Superconducting materials: superconductivity on the verge of catastrophe.

PMID- 16652116
TI  - Surface science: excitement of molecules on surfaces.

PMID- 16652117
TI  - Material witness: higher Tc?

PMID- 16652118
TI  - Bio-functionalized quantum dots: tinkering with cell machinery.

PMID- 16652119
TI  - Ethanol-responsive genes: identification of transcription factors and their role
      in metabolomics.
AB  - Transcription factors (TFs) and their combinatorial control on cis-regulatory
      elements play critical role in the co-expression of genes. This affects the
      interaction of genes in the transcriptome and thus may affect signals that
      cascade through cellular pathways. Using a combination of bioinformatic
      approaches, we sought to identify such common combinations of TFs in a set of
      ethanol-responsive (ER) genes and assess the role of ethanol in affecting
      multiple pathways through their co-regulation. Our results show that the
      metallothionein genes are regulated by TF motifs cAMP responsive element binding
      protein (CREB) and metal-activated transcription factor 1 and primarily involved
      in zinc ion homeostasis. We have also identified new target genes, Synaptojanin 1
      and tryptophan hydroxylase 1, potentially regulated by this module. Altered
      arrangement of TF-binding sites in the module may direct the action of these and
      other target genes in intracellular signaling cascades, cell growth and/or
      maintenance. In addition to CREB, other key TFs identified are ecotropic viral
      integration site-1 and SP1. These modulate the contribution of the target ER
      genes in cell cycle regulation and apoptosis or programmed cell death. Multiple
      lines of evidence confirm the above findings and indicate that different groups
      of ER genes are involved in different biological processes and their co
      regulation most likely results from different sets of regulatory modules. These
      findings associate the role of the ER genes studied and their potential TF
      modules with alcohol response pathways and phenotypes.

PMID- 16652120
TI  - The drug diagnostic co-development concept paper: commentary from the 3rd FDA-DIA
      PWG-PhRMA-BIO Pharmacogenomics Workshop.
AB  - At the Washington DC Pharmacogenomics in Drug Development and Regulatory Decision
      Making: Workshop III - Three Years of Promise, Proposals and Progress on
      Optimizing the Benefit/Risk of Medicines (11-13 April 2005), one break-out
      session (Track 2) focused on co-development of therapeutic drug and diagnostic
      products. The Food and Drug Administration (FDA) released a draft concept paper
      shortly before the workshop was to convene. Track 2 was a forum for initial
      discussion of the content of the concept paper, and industry's initial reactions.
      After the workshop, formal commentaries on the co-development concept paper were
      submitted by several trade associations (e.g., Pharmaceutical Research and
      Manufacturers of America (PhRMA), Advanced Medical Technology Association
      (AdvaMed), American Association for Clinical Chemistry) and individual companies
      to FDA's Docket No. 2004N-0279. This paper includes a summary of the key features
      of the draft concept paper, the discussion in Track 2 of the April, 2005 meeting
      and highlights of the industry comments submitted to the FDA docket following the
      meeting.

PMID- 16652121
TI  - Myofibroblastic stromal reaction and expression of tenascin-C and laminin in
      prostate adenocarcinoma.
AB  - The aim of this study was to analyse relationship between changes of the stroma
      and expression of tenascin-C (TN-C) and laminin in prostate carcinoma. Tenascin-C
      immunostaining was increased, and laminin decreased in carcinomas compared with
      peritumoral tissue and benign prostate hyperplasia (P<0.05). Statistical analysis
      confirmed connection between stromal changes and TN-C expression in prostate
      carcinoma (P<0.05). Gleason pattern 3 carcinomas showed more pronounced stromal
      reaction and TN-C expression compared with Gleason pattern 4 carcinomas (P<0.05).
      The main cells in prostate cancer stroma are myofibroblasts that are also
      responsible for tenascin production. Degradation of laminin was not connected
      with myofibroblastic stromal changes.

PMID- 16652122
TI  - The effect of sibutramine-assisted weight loss in men with obstructive sleep
      apnoea.
AB  - OBJECTIVE: Obstructive sleep apnoea (OSA) occurs frequently in obese patients and
      may be reversible with weight loss. Obstructive sleep apnoea and obesity are both
      independent risk factors for hypertension and increased sympathetic activity.
      Sibutramine has been increasingly used in the management of obesity, but is
      relatively contraindicated in patients with hypertension. No studies have
      investigated the effect of sibutramine on OSA, blood pressure and heart rate. We
      aimed to assess the changes in OSA and cardiovascular parameters in obese men
      with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL).
      DESIGN: Open uncontrolled cohort study of obese male subjects with OSA in an SIB
      WL. SUBJECTS: Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle
      aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/
      3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the
      study. RESULTS: At 6 months, there was significant weight loss (8.3+/-4.7 kg,
      P<0.0001), as well as a reduction in waist and neck circumference and sagittal
      height (all P<0.0001). These changes were accompanied by a reduction in OSA
      severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both
      P<0.0001). There was no significant change to systolic (P=0.07) or diastolic
      blood pressure (P=0.87); however, there was a mild rise in resting heart rate
      (P<0.0001). CONCLUSION: Moderate (approximately 10%) weight loss with SIB-WL
      results in improvement in OSA severity without increase in blood pressure in
      closely monitored OSA subjects.

PMID- 16652123
TI  - Does physical activity equally predict gain in fat mass among obese and nonobese
      young adults?
AB  - BACKGROUND: Differences in energy metabolism and physical activity (PA) may
      contribute to the long-term regulation of body weight (BW). OBJECTIVE: To examine
      the associations between metabolic determinants, energy expenditure and
      objectively measured components of PA with change in BW and fat mass (FM).
      DESIGN: Prospective (4 years.), case-control study in obese (n=13) and normal
      weight (n=15) young adults. MEASUREMENTS: At baseline, we measured resting
      metabolic rate, substrate oxidation, movement economy (ml O(2) kg(-1) min(-1)),
      aerobic fitness (VO(2max)), total and PA energy expenditure by doubly labelled
      water, and PA by accelerometry. Fat mass was measured by DXA. At follow-up we
      repeated our measurements of PA and FM. RESULTS: Fat mass increased significantly
      (P<0.001) in both groups. Physical activity did not change between baseline and
      'follow up'. Change in overall PA (counts per minute) was inversely associated
      with change in BW and (beta=-0.0124, P=0.054) and FM (beta=-0.008, P=0.04). Post
      hoc analyses suggested that this association was explained by changes in the
      normal weight group only (beta=-0.01; P=0.008; and beta=-0.0097; P=0.009, for BW
      and FM, respectively). Metabolic determinants, energy expenditure estimates and
      subcomponents of PA (i.e. time spent at different intensity levels) were not
      significantly associated with change in BW or FM. CONCLUSION: Our results suggest
      an independent association between PA and FM. However, this association may
      differ depending on obesity status. The gain in FM, without any change in PA, may
      suggest that dietary intake is the major contributor to the positive energy
      balance.

PMID- 16652124
TI  - Regional differences in abdominal fat loss.
AB  - OBJECTIVE: This study determined if the magnetic resonance imaging (MRI) protocol
      used alters the estimation of change in abdominal fat with weight loss in obese
      type 2 diabetic women. This study also examined if there is a uniform fat loss
      across the abdomen. METHODS AND PROCEDURES: Thirty-three obese postmenopausal
      women with type 2 diabetes (age 50-70 years, body mass index>30 kg/m(2)) had a
      total abdominal MRI scan pre- and post weight loss intervention. Three different
      MRI analysis protocols were used and compared: a single slice at L(2)-L(3) vs
      five slices (centered at L(4)-L(5)) vs all abdominal slices. In addition, the
      total abdominal scan was divided into four regions (four slices each) with region
      3 (critical region) including the traditionally studied L(2)-L(3), and regions 1
      and 2 superior and region 4 inferior to critical region 3. Analysis of variance
      (ANOVA) with repeated measures was used to compare the influence of weight loss
      on abdominal fat measured both regionally and using the varying number of MR
      slices. RESULTS: At baseline, the ratio of visceral adipose tissue:subcutaneous
      adipose tissue (VAT:SAT) was significantly lower using the single-slice method
      compared to five slices and the total abdomen (P<0.01). Using the single-slice
      method, a lower %VAT was found than with the other methods (P<0.01). In regions
      1, 2, 3, and 4, the absolute change in total fat was 122+/-50, 182+/-48, 182+/
      55, and 155+/-40 cm(3), respectively. The regional difference in abdominal fat
      patterning revealed that the critical region (region 3) had a smaller VAT:SAT
      ratio than regions 1 and 2 (P<0.05), and the ratio at region 4 was smaller than
      region 3 (P<0.05). Weight loss resulted in a decrease in the VAT:SAT ratio
      (P<0.05) for regions 3 and 4 but not for regions 1 and 2. CONCLUSIONS: The number
      of MR slices analyzed yields differential result in relative VAT distribution.
      Regional differences in abdominal fat loss occur with a greater relative VAT loss
      in the critical region, thus if only the critical region is analyzed the overall
      VAT loss induced by weight loss intervention may be overestimated.

PMID- 16652125
TI  - Viral mRNA expression but not DNA replication is required for lipogenic effect of
      human adenovirus Ad-36 in preadipocytes.
AB  - OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and shows
      association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and
      human preadipocytes, without cell lysis, a characteristic that may contribute to
      its adipogenic effect observed in vivo. Ad-2, another human adenovirus is
      nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human
      obesity. The objective of this study was to determine the adipogenic roles of
      viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2
      on preadipocyte differentiation. METHODS: This study determined the duration of
      selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes
      differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an
      antiadenoviral agent. RESULTS: The results showed that Ad-36, but not Ad-2,
      expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation
      and very low levels persisted after day 7. Despite the viral mRNA expression, Ad
      36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease
      in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced
      the adipogenic effect of the virus. CONCLUSION: In conclusion, viral mRNA
      expression, although transient, is a prerequisite for enhancing differentiation
      of preadipocytes by Ad-36. Viral DNA replication was not required for the effect.
      This is the first evidence for the role of gene expression of an adipogenic human
      virus in enhancing preadipocytes differentiation. This study provides the basis
      for further understanding novel regulatory modulators of preadipocytes
      differentiation.

PMID- 16652126
TI  - Sitting time and socio-economic differences in overweight and obesity.
AB  - OBJECTIVES: To examine (1) the inter-relationships between socio-economic status
      (SES), physical activity, three different domains of sitting time (weekday,
      weekend day and leisure-time sitting), and being overweight or obese (body mass
      index>/=25 kg/m(2)); and (2) the potential mediation effects of sitting time in
      the relationship between socio-economic factors and being overweight or obese in
      working Australian adults. DESIGN: Observational epidemiological study. SUBJECTS:
      One thousand forty eight working adults. Using a multistage sampling design on
      neighbourhood SES, participants were from high and low SES neighbourhoods of an
      Australian capital city. MEASUREMENTS: Neighbourhood SES was assessed using
      census data; individual SES was based on self-reported educational attainment and
      household income. There were three sitting time variables: sitting time on
      weekdays, weekend days and in leisure time. Overweight and obesity were
      determined using self-reported body weight and height. RESULTS: Gender, age,
      neighbourhood SES, education, working hours and physical activity were
      independently associated with weekday, weekend day and leisure-related sitting
      time. With the exception of education and working hours, these variables were
      also independently associated with being overweight or obese. Leisure-time
      sitting was found to be a mediator in the relationships between gender, education
      and being overweight or obese. CONCLUSION: Strategies to promote less sitting in
      leisure time are required to combat overweight and obesity in Australian adults,
      especially among those from low SES neighbourhoods, and among those with high
      levels of education and income who work long hours.

PMID- 16652127
TI  - The G1057D polymorphism of IRS-2 gene and its relationship with obesity in
      conferring susceptibility to type 2 diabetes in Asian Indians.
AB  - OBJECTIVE: To investigate the association of insulin receptor substrate-2 (IRS-2)
      G1057D polymorphism with type 2 diabetes and obesity in Asian Indians. METHODS:
      The study comprised of 1193 normal glucose tolerant (NGT) subjects and 1018
      subjects with type 2 diabetes, aged >/=20 years with an average body mass index
      of 23.7+/-4.6 and 25.3+/-4.2 kg/m(2), respectively. The subjects were unrelated
      and randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a
      population-based study in Chennai in southern India. The G1057D polymorphism of
      the IRS-2 gene was genotyped using PCR-RFLP assay. RESULTS: The genotype
      frequency of the IRS-2 G1057D polymorphism was significantly different between
      the NGT and type 2 diabetic groups (P=0.0007) in the total study subjects and
      among the obese subjects (P=0.00007). Logistic regression analysis showed that
      the DD genotype showed an increased susceptibility to diabetes with an odds ratio
      (adjusted for age and sex) of 2.19 (95% CI: 1.34-3.57, P=0.002) when compared to
      the GG+GD genotype, among the obese subjects, but not in non obese subjects. In
      order to explore possible interaction with obesity, logistic regression analysis
      was performed and the coefficient corresponding to the interaction parameter
      (genotype x obesity) was significant (P=0.0001). CONCLUSION: In Asian Indians,
      the DD genotype increases susceptibility to type 2 diabetes by interacting with
      obesity.

PMID- 16652128
TI  - Is China facing an obesity epidemic and the consequences? The trends in obesity
      and chronic disease in China.
AB  - BACKGROUND: Over the past two decades, China has enjoyed impressive economic
      development, and her citizens have experienced many remarked changes in their
      lifestyle. These changes are often associated with an increase in obesity and
      chronic disease. METHODS: In this meta-analysis, based on nationally
      representative data, we studied the current prevalence of obesity and the trends
      in obesity, mortality and morbidity in China. RESULTS: Between 1992 and 2002, the
      prevalence of overweight and obesity increased in all gender and age groups and
      in all geographic areas. Using the World Health Organization body mass index cut
      points, the combined prevalence of overweight and obesity increased from 14.6 to
      21.8%. The Chinese obesity standard shows an increase from 20.0 to 29.9%. The
      annual increase rate was highest in men aged 18-44 years and women aged 45-59
      years (approximately 1.6 and 1.0% points, respectively). In general, male
      subjects, urban residents, and high-income groups had a greater increase. With
      the increase in overweight and obesity, obesity-, and diet-related chronic
      diseases (e.g., hypertension, cardiovascular disease (CVD), and type 2 diabetes)
      also increased over the past decade and became a more important preventable cause
      of death. Hypertension increased from 14.4% in 1991 to 18.8% in 2002 in adults;
      in older adults aged 35-74 years, it increased from 19.7 to 28.6%. Between 1993
      and 2003, the prevalence of CVD increased from 31.4 to 50.0%; diabetes increased
      from 1.9 to 5.6%. During 1990-2003, although total mortality rate (per 100 000)
      decreased, overall the mortality rate and contribution (as percentages) to total
      death of obesity-related chronic disease increased, in particular, in rural
      areas. Mortality rate (per 100 000) of CVD increased from 128 to 145 and its
      contribution to total death, 27 to 32%, in rural areas; the figures decreased
      slightly in urban areas. The mortality rate of 'nutrition, endocrinology and
      metabolism-related disease' (NEMD) increased in both rural and urban areas
      between 1990 and 2000, 8.0 to 10.6 and 4.9 to 5.3, respectively. The current
      prevalence of hypertension, dyslipidaemia, metabolic syndrome, and diabetes among
      Chinese adults is approximately 20, 20, 15, and 3%, respectively. CONCLUSION: The
      prevalence of overweight and obesity and obesity-related chronic diseases have
      increased in China in the past decade. Our findings provide useful information
      for the projection of future trends and the formulation of national strategies
      and programmes that can address the challenges of the growing obesity and chronic
      disease epidemic.

PMID- 16652129
TI  - Energy expenditure of genuine laughter.
AB  - OBJECTIVE: To measure energy expenditure (EE) and heart rate (HR) during genuine
      laughter. DESIGN: Experimental trial of viewing film clips in four cycles either
      intended to evoke laughter (humorous -10 min) or unlikely to elicit laughter (not
      humorous -5 min) under strictly controlled conditions of a whole-room indirect
      calorimeter equipped with audio recording system. PARTICIPANTS: Forty five adult
      friend dyads in either same-sex male (n=7), same-sex female (n=21) and mix-sex
      male-female (n=17); age 18-34 years; body mass index 24.7+/-4.9 (range 17.9
      41.1). MEASUREMENTS: Energy expenditure in a whole-room indirect calorimeter, HR
      using Polar HR monitor. Laugh rate, duration and type from digitized audio data
      using a computerized system and synchronized with HR and EE results. RESULTS:
      Laughter EE was 0.79+/-1.30 kJ/min (0.19+/-0.31 kcal/min) higher than resting EE
      (P<0.001, 95% confidence interval=0.75-0.88 kJ/min), ranging from -2.52 to 9.67
      kJ/min (-0.60-2.31 kcal/min). Heart rate during laughter segments increased above
      resting by 2.1+/-3.8 beats/min, ranging from -7.6 to 26.8 beats/min. Laughter EE
      was correlated with HR (r (s)=0.250, P<0.01). Both laughter EE and HR were
      positively correlated with laughter duration (r (s)=0.282 and 0.337, both
      P<0.001) and rate (r(s)=0.256 and 0.298, both P<0.001). CONCLUSION: Genuine
      voiced laughter causes a 10-20% increase in EE and HR above resting values, which
      means that 10-15 minutes of laughter per day could increase total EE by 10-40 kJ
      (2-10 kcal) [corrected].

PMID- 16652130
TI  - Body fat loss achieved by stimulation of thermogenesis by a combination of
      bioactive food ingredients: a placebo-controlled, double-blind 8-week
      intervention in obese subjects.
AB  - BACKGROUND: A combination of tyrosine, capsaicin, catechines and caffeine may
      stimulate the sympathetic nervous system and promote satiety, lipolysis and
      thermogenesis. In addition, dietary calcium may increase fecal fat excretion.
      OBJECTIVE: To investigate the acute and subchronic effect of a supplement
      containing the above mentioned agents or placebo taken t.i.d on thermogenesis,
      body fat loss and fecal fat excretion. DESIGN: In total, 80 overweight-obese
      subjects ((body mass index) 31.2+/-2.5 kg/m(2), mean+/-s.d.) underwent an initial
      4-week hypocaloric diet (3.4 MJ/day). Those who lost>4% body weight were
      instructed to consume a hypocaloric diet (-1.3 MJ/day) and were randomized to
      receive either placebo (n=23) or bioactive supplement (n=57) in a double-blind, 8
      week intervention. The thermogenic effect of the compound was tested at the first
      and last day of intervention, and blood pressure, heart rate, body weight and
      composition were assessed. RESULTS: Weight loss during the induction phase was
      6.8+/-1.9 kg. At the first exposure the thermogenic effect of the bioactive
      supplement exceeded that of placebo by 87.3 kJ/4 h (95%CI: 50.9;123.7, P=0.005)
      and after 8 weeks this effect was sustained (85.5 kJ/4 h (47.6;123.4), P=0.03).
      Body fat mass decreased more in the supplement group by 0.9 kg (0.5; 1.3)
      compared with placebo (P<0.05). The bioactive supplement had no effect on fecal
      fat excretion, blood pressure or heart rate. CONCLUSION: The bioactive supplement
      increased 4-h thermogenesis by 90 kJ more than placebo, and the effect was
      maintained after 8 weeks and accompanied by a slight reduction in fat mass. These
      bioactive components may support weight maintenance after a hypocaloric diet.

PMID- 16652131
TI  - Musculoskeletal findings in obese subjects before and after weight loss following
      bariatric surgery.
AB  - OBJECTIVE: To determine the point prevalence of painful musculoskeletal (MSK)
      conditions in obese subjects before and after weight loss following bariatric
      surgery. DESIGN: Longitudinal, interventional, unblended. SUBJECTS: Forty-eight
      obese subjects (47 women, one man, mean age 44+/-9 years; mean body mass index
      (BMI) 51+/-8 kg/m(2)) recruited from an academic medical center bariatric surgery
      program. MEASUREMENTS: Comorbid medical conditions; MSK findings; BMI; Western
      Ontario McMaster Osteoarthritis Index (WOMAC) for pain, stiffness and function;
      and SF-36 for quality of life. METHODS: Consecutive subjects were recruited from
      the University Hospitals of Cleveland Bariatric Surgery Program. Musculoskeletal
      signs and symptoms and non-MSK comorbid conditions were documented at baseline
      and at follow-up. SUBJECTS completed the SF-36 and the WOMAC questionnaires.
      Analyses were carried out for each MSK site, fibromyalgia syndrome (FMS) and for
      the cumulative effect on the spine, upper and lower extremities. The impact of
      change in comorbid medical conditions, BMI, physical and mental health domains of
      the SF-36 on the WOMAC pain subscale score was evaluated. SF-36 outcomes were
      compared to normal published controls. RESULTS: Forty-eight subjects were
      available for baseline and a follow-up assessment 6-12 months after gastric
      bypass surgery. They lost an average of 41+/-15 kg and the mean BMI decreased
      from 51+/-8 to 36+/-7 kg/m(2). Baseline comorbid medical conditions were present
      in 96% before surgery and 23% after weight loss. There was an increased
      prevalence of painful MSK conditions at baseline compared to general population
      frequencies. Musculoskeletal complaints had been present in 100% of obese
      subjects before, and 23% after weight loss. The greatest improvements occurred in
      the cervical and lumbar spine, the foot and in FMS (decreased by 90, 83, 83 and
      92%, respectively). Seventy-nine percent had upper extremity MSK conditions
      before and 40% after weight loss. Before surgery, 100% had lower extremity MSK
      conditions and only 37% did after weight loss. The WOMAC subscale and composite
      scores all improved significantly, as did the SF-36((R)). Change in BMI was the
      main factor impacting the WOMAC pain score. CONCLUSION: There was a higher
      frequency of multiple MSK complaints, including non-weight-bearing sites compared
      to historical controls, before surgery, which decreased significantly at most
      sites following weight loss and physical activity. These benefits may improve
      further, as weight loss may continue for up to 24 months. The benefits seen with
      weight loss indicate that prevention and treatment of obesity can improve MSK
      health and function.

PMID- 16652132
TI  - Subcutaneous adipose tissue cytokine production is not responsible for the
      restoration of systemic inflammation markers during weight loss.
AB  - CONTEXT: It has been suggested that weight loss can improve systemic inflammation
      associated with obesity by decreasing the adipose production of pro-inflammatory
      cytokines. This suggestion, however, remains controversial. OBJECTIVE: To analyse
      the effect of weight loss on peripheral inflammatory markers and subcutaneous
      adipocytokine production. DESIGN: Patients were studied at baseline, at the end
      of the weight loss period, and after 2 weeks of weight stabilisation. SUBJECTS:
      Nineteen morbid obese non-diabetic patients and 20 lean control subjects.
      INTERVENTION: During the weight loss period patients followed a 6-week low
      calorie diet. MEASUREMENTS: Plasma levels of inflammatory markers, maximal in
      vitro whole-blood cytokine production, subcutaneous adipose tissue expression and
      content of several cytokines. RESULTS: Obese subjects had higher circulating
      levels of C reactive protein (CRP), serum amyloid A (SAA), interleukin IL-6, IL-1
      and soluble tumor necrosis factor receptors (sTNFR). Weight loss was associated
      with a significant decrease in CRP, SAA, leucocytes and plasma IL-6. Maximal in
      vitro cytokine production of IL-1 and sTNFR1 increased during this period. Weight
      loss did not induce significant changes in the adipose concentrations of IL-6, IL
      1 or sTNF-receptors. However, adipose expression of IL-6, IL-1, TNFalpha,
      membrane cofactor protein-1 and adiponectin increased at the end of the weight
      loss period. During weight maintenance, circulating inflammatory parameters
      increased and in some cases returned to baseline. CONCLUSIONS: A low-calorie diet
      is associated with an improvement in the systemic inflammatory status. This seems
      to be due to energy restriction rather than to adipose mass loss, since
      inflammatory levels return to baseline soon after weight stabilisation.
      Furthermore, a negative energy balance and fat mobilisation are associated with
      increased subcutaneous cytokine adipose expression.

PMID- 16652133
TI  - Cardiovascular risk factors and anthropometric measurements of adolescent body
      composition: a cross-sectional analysis of the Third National Health and
      Nutrition Examination Survey.
AB  - OBJECTIVE: To assess the association between certain cardiovascular risk factors
      that are commonly clustered among individuals with insulin resistance syndrome
      (IRS) and adolescents' body composition measurements. METHODS: We examined a
      total of 1068 adolescents aged 12-16 years from the Third National Health and
      Nutrition Examination Survey. The sex-specific third tertiles of glucose,
      triglycerides, systolic blood pressure and first tertile of high-density
      lipoprotein (HDL) cholesterol were used to classify the presence of each IRS
      component. We compared adolescents with none, one, two and three/four IRS
      components across a series of body composition measurements and lipid profile.
      RESULTS: About 18% of the adolescents had three or four IRS components. Overall,
      IRS among adolescents is more likely to be associated with body weight and
      measurements related to body girths and less likely to be associated with the
      measurements related to body lengths. Multivariate analysis results showed that
      the odds of being at increased risk of obesity (body mass index z-score> 0.85)
      were significantly greater among those with two (odds ratio (OR)=4.5; 95% CI 2.5
      8.2) and three/four (OR=8.9, 95% CI 4.5-17.5) IRS components compared to those
      without any IRS components. Across sex, the level of non-HDL cholesterol was
      significantly higher among adolescents with more IRS components (P for trends
      <0.05). CONCLUSIONS: The clustered cardiovascular risk factors are strongly
      associated with an increased risk of obesity and higher levels of non-HDL
      cholesterol among adolescents.

PMID- 16652134
TI  - Association of peroxisome proliferator-activated receptor delta +294T/C with body
      mass index and interaction with peroxisome proliferator-activated receptor alpha
      L162V.
AB  - OBJECTIVE: To investigate the association of a polymorphism at position 294
      (+294T/C) in the Peroxisome Proliferator-activated Receptor delta (PPARdelta)
      with body mass index (BMI) and the additional role of a gene-to-gene interaction
      between PPARdelta, PPARalpha and PPARgamma. DESIGN: An association between
      genetic variations in PPARdelta, PPARalpha and PPARgamma and indices of obesity
      and metabolism. SUBJECTS: A group of 462 moderately obese (mean BMI 28.9+/-7.7)
      and dyslipidemic, middle-aged (mean age 43.9+/-13.7), Caucasion men and women.
      MEASUREMENTS: The three most frequent single-nucleotide-polymorphisms (snp) in
      PPARdelta (+294T/C), PPARalpha (L162V) and PPARgamma (P12A) were genotyped and
      associated with clinical parameters. RESULTS: The C allele in PPARdelta was
      significantly associated with a lower body mass index. Moreover an interaction
      between the polymorphisms in PPARalpha and PPARdelta on body weight could be
      demonstrated. CONCLUSION: Our data provide further evidence for an involvement of
      PPARdelta in the regulation of BMI.

PMID- 16652135
TI  - Safety and efficacy of NT, an herbal supplement, in treating human obesity.
AB  - OBJECTIVE: A human pilot study testing the safety and effectiveness of NT (Number
      Ten), a dietary herbal supplement made from rhubarb, ginger, astragulus, red sage
      and turmeric, to reduce food intake and cause weight loss. RESEARCH METHODS AND
      PROCEDURES: A total of 24 healthy women, 18-60 years, body mass index 25-35
      kg/m(2) on no chronic medication were randomized to four groups of six: (1) oral
      freeze-dried NT 6 gm/day, (2) bed-dried NT 6 gm/day, (3) freeze-dried NT 12
      gm/day or (4) placebo. Number Ten dose was escalated over 3 weeks and maintained
      for 8 weeks on a 700 kcal/day diet below maintenance. Food intake was measured at
      baseline and 4 weeks. Safety parameters were monitored weekly during dose
      escalation, week 6 and week 12. RESULTS: Weight loss was 1.8 kg for placebo and
      0.4 kg for 500 mg NT whereas the 250 mg bed- and freeze-dried NT gained 0.43 and
      0.87 kg, respectively (P=NS). The food intake increased 74 kcal with 250 mg
      freeze-dried NT and decreased 193.7 kcal with 500 mg freeze-dried NT (P<0.01).
      There was a dose-related incidence of loose stools in the NT groups, but no other
      toxicity was seen. Number Ten was found to contain sennosides, known laxatives
      and gallic acid, which is known to give weight loss in rodents. DISCUSSION: The
      human dose equivalent of NT used in this study was & frac16; and & frac112; of
      that shown to give well-tolerated weight loss in rodents. Number Ten will not be
      an effective dietary herbal supplement for the treatment of obesity owing to dose
      limiting gastrointestinal toxicity.

PMID- 16652136
TI  - Joint association of coffee consumption and other factors to the risk of type 2
      diabetes: a prospective study in Finland.
AB  - OBJECTIVE: To examine joint associations of coffee consumption and other factors
      (including physical activity, obesity and alcohol consumption) with the risk of
      type 2 diabetes. DESIGN: Prospective follow-up study. SUBJECTS: In all, 10 188
      Finnish men and 11 197 women aged 35-74 years without a history of stroke,
      coronary heart disease or diabetes at baseline. MEASUREMENT: A self-administered
      questionnaire data on coffee, tea, alcohol and other food consumption, physical
      activity, smoking, socio-economic factors and medical history, together with
      measured height, weight and blood pressure using standardized protocol. RESULTS:
      During a mean follow-up of 13.4 years, there were 964 incident cases of type 2
      diabetes. Multivariate-adjusted (age, study year, systolic blood pressure,
      education, smoking, physical activity, body mass index (BMI) and fruit,
      vegetable, sausage, bread, alcohol and tea consumption) hazard ratio of type 2
      diabetes in participants who drank 0-2, 3-6 and > or =7 cups of coffee were 1.00,
      0.77 and 0.66 (P=0.022 for trend) in men, 1.00, 0.71 and 0.52 (P=0.001 for trend)
      in women, and 1.00, 0.75 and 0.61 (P<0.001 for trend) in men and women combined
      (adjusted also for sex), respectively. This inverse association was consistent in
      subjects with any joint levels of physical activity and BMI, and in alcohol
      drinkers and non-drinkers. Among obese and inactive people, coffee drinking of
      seven cups or more daily reduced the risk of type 2 diabetes to half.
      CONCLUSIONS: Coffee drinking was associated with a reduced risk of type 2
      diabetes in both men and women, and this association was observed regardless of
      the levels of physical activity, BMI and alcohol consumption.

PMID- 16652137
TI  - Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying
      relationships according to diabetes type.
AB  - OBJECTIVE: To compare the relationships between markers of total and regional
      adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic
      subjects and their respective nondiabetic controls, and to document these
      relationships in type 1 diabetic subjects. DESIGN: Cross-sectional study.
      SUBJECTS: In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control
      subjects. Each diabetic group was matched for age, sex and body mass index with
      its respective nondiabetic control group. MEASUREMENTS: Measures of body
      composition (hydrodensitometry), fat distribution (waist circumference, abdominal
      and mid-thigh computed tomography scans) and blood lipid profiles were assessed.
      RESULTS: Low attenuation mid-thigh muscle surface correlated similarly with
      markers of adiposity and body composition in all groups, regardless of diabetes
      status, except for visceral adipose tissue and waist circumference. Indeed,
      relationships between visceral adiposity and muscle adiposity were significantly
      stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes).
      In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%),
      daily insulin requirements tended to correlate with low attenuation mid-thigh
      muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not
      with glycemic control (HbA(1c)). CONCLUSION: This study suggests that the
      relationship of central adiposity and muscle adiposity is modulated by diabetes
      status and is stronger in the insulin resistant diabetes type (type 2 diabetes).
      In well-controlled nonobese type 1 diabetic subjects, the relationship between
      muscle fat accumulation and insulin sensitivity was also maintained.

PMID- 16652138
TI  - The versatile epsilon-proteobacteria: key players in sulphidic habitats.
AB  - The epsilon-proteobacteria have recently been recognized as globally ubiquitous
      in modern marine and terrestrial ecosystems, and have had a significant role in
      biogeochemical and geological processes throughout Earth's history. To place this
      newly expanded group, which consists mainly of uncultured representatives, in an
      evolutionary context, we present an overview of the taxonomic classification for
      the class, review ecological and metabolic data in key sulphidic habitats and
      consider the ecological and geological potential of the epsilon-proteobacteria in
      modern and ancient systems. These integrated perspectives provide a framework for
      future culture- and genomic-based studies.

PMID- 16652139
TI  - Genomic instability during Myc-induced lymphomagenesis in the bursa of Fabricius.
AB  - Retroviral vector-mediated overexpression of c-myc in embryonic bursal precursors
      induces multi-staged tumorigenesis beginning with preneoplastic-transformed
      follicles (TF) and progressing to clonal metastatic B-cell lymphomas. Using a 13K
      chicken cDNA microarray, specifically enriched for chicken immune system
      expressed sequence tagged (ESTs), we carried out array-based comparative genomic
      hybridization (array-CGH) and detected significant DNA copy number change at many
      loci on most or all chromosomes in both early TF and end-stage lymphomas.
      Formation of long palindromes, through breakage-fusion-bridge cycles, is thought
      to play an early role in gene amplification. Employing genome-wide analysis of
      palindrome formation (GAPF), we detected extensive palindrome formation in early
      TF and end-stage lymphomas. The population of loci showing amplification by array
      CGH was enriched for palindromes detected by GAPF providing strong evidence for
      genetic instability early in Myc-induced tumorigenesis and further support for
      the role of palindromes in gene amplification. Comparing gene copy number change
      and RNA expression changes profiled on the same cDNA array, we detected very
      little consistent contribution of gene copy number change to RNA expression
      changes. Palindromic loci in TF and tumors, however, were expressed, many at high
      levels, suggesting an abundance of RNA species with long double-stranded segments
      generated during tumorigenesis.

PMID- 16652140
TI  - siRNA-mediated AML1/MTG8 depletion affects differentiation and proliferation
      associated gene expression in t(8;21)-positive cell lines and primary AML blasts.
AB  - The chromosomal translocation t(8;21) is associated with 10-15% of all cases of
      acute myeloid leukaemia (AML). The resultant fusion protein AML1/MTG8 interferes
      with haematopoietic gene expression and is an important regulator of
      leukaemogenesis. We studied the effects of small interfering RNA (siRNA)-mediated
      AML1/MTG8 depletion on global gene expression in t(8;21)-positive leukaemic cell
      lines and in primary AML blasts using cDNA arrays, oligonucleotide arrays and
      real-time reverse transcription-polymerase chain reaction (RT-PCR). Suppression
      of AML1/MTG8 results in the increased expression of genes associated with myeloid
      differentiation, such as AZU1, BPI, CTSG, LYZ and RNASE2 as well as of
      antiproliferative genes such as IGFBP7, MS4A3 and SLA both in blasts and in cell
      lines. Furthermore, expression levels of several genes affiliated with drug
      resistance or indicative of poor prognosis AML (BAALC, CD34, PRG2, TSPAN7) are
      affected by AML1/MTG8 depletion. In conclusion, siRNA-mediated suppression of
      AML1/MTG8 cause very similar changes in gene expression pattern in t(8;21)
      positive cell lines and in primary AML blasts. Furthermore, the results suggest
      that the specific targeting of AML1/MTG8 function may be a promising approach for
      complementing existing treatment strategies.

PMID- 16652141
TI  - Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human
      hepatocellular carcinoma and linked to the malignant phenotype of tumors.
AB  - Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway
      has been shown to be involved in the progression of human hepatocellular
      carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is
      poorly understood. Recently, we identified Sprouty-related protein with
      Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a
      physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found
      that the expression levels of Spred-1 and -2 in human HCC tissue were frequently
      decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred
      expression levels in HCC tissue were inversely correlated with the incidence of
      tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell
      proliferation in vitro and in vivo, which was associated with reduced ERK
      activation. Spred-1 overexpression also reduced the secretion of matrix
      metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor
      invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated
      HCC cell motility. These data indicate that the reduction of Spred expression in
      HCC is one of the causes of the acquisition of malignant features. Thus, Spred
      could be not only a novel prognostic factor but also a new therapeutic target for
      human HCC.

PMID- 16652142
TI  - Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor
      tyrosine kinase.
AB  - Mer (MerTK) is a receptor tyrosine kinase important in platelet aggregation, as
      well as macrophage cytokine secretion and clearance of apoptotic cells. Mer is
      not normally expressed in thymocytes or lymphocytes; however, ectopic Mer RNA
      transcript and protein expression is found in a subset of acute lymphoblastic
      leukemia cell lines and patient samples, suggesting a role in leukemogenesis. To
      investigate the oncogenic potential of Mer in vivo, we created a transgenic mouse
      line (Mer(Tg)) that expresses Mer in the hematopoietic lineage under control of
      the Vav promoter. Ectopic expression and activation of the transgenic Mer protein
      was demonstrated in lymphocytes and thymocytes of the Mer(Tg) mice. At 12-24
      months of age, greater than 55% of the Mer(Tg) mice, compared to 12% of the wild
      type, developed adenopathy, hepatosplenomegaly, and circulating lymphoblasts.
      Histopathological analysis and flow cytometry were consistent with T-cell
      lymphoblastic leukemia/lymphoma. Mer may contribute to leukemogenesis by
      activation of Akt and ERK1/2 anti-apoptotic signals, which were upregulated in
      Mer(Tg) mice. Additionally, a significant survival advantage was noted in Mer(Tg)
      lymphocytes compared to wild-type lymphocytes after dexamethasone treatment.
      These data suggest that Mer plays a cooperative role in leukemogenesis and may be
      an effective target for biologically based leukemia/lymphoma therapy.

PMID- 16652143
TI  - Novel role of Stat1 in the development of docetaxel resistance in prostate tumor
      cells.
AB  - A major obstacle for clinicians in the treatment of advanced prostate cancer is
      the inevitable progression to chemoresistance, especially to docetaxel. It is
      essential to understand the molecular events that lead to docetaxel resistance in
      order to identify means to prevent or interfere with chemoresistance. In initial
      attempts to detect these events, we analysed genomic differences between non
      resistant and docetaxel-resistant prostate tumor cells and, of the genes
      modulated by docetaxel treatment, we observed Stat1 and clusterin gene expression
      heightened in the resistant phenotype. In this study, we provide biochemical and
      biological evidence that these two gene products are related. Stat1 and clusterin
      protein expression was induced upon docetaxel treatment of DU145 cells and highly
      overexpressed in the docetaxel-resistant DU145 cells (DU145-DR). The increase in
      total Stat1 corresponded to an increase in phosphorylated Stat1. Interestingly,
      there was no detectable difference between DU145 and DU145-DR cells expression of
      total Stat3 and phosphorylated Stat3. Treatment of DU145-DR cells with small
      interfering RNA targeted for Stat1 not only resulted in the knockdown of Stat1
      expression, but it also caused the inhibition of clusterin expression. Thus,
      Stat1 appears to play a key role in the regulation of clusterin. Remarkably,
      inhibition of Stat1 or clusterin expression resulted in the re-sensitization of
      DU145-DR cells to docetaxel. These results offer the first evidence that Stat1,
      and its subsequent regulation of clusterin, are essential for docetaxel
      resistance in prostate cancer. Targeting this pathway could be a potential
      therapeutic means for intervention of docetaxel resistance.

PMID- 16652144
TI  - Oxidative stress induces a prolonged but reversible arrest in p53-null cancer
      cells, involving a Chk1-dependent G2 checkpoint.
AB  - Reactive oxygen species (ROS), the principal mediators of oxidative stress,
      induce responses such as apoptosis or permanent growth arrest/senescence in
      normal cells. Moreover, p53 activation itself contributes to ROS accumulation.
      Here we show that treatment of p53-null cancer cells with sublethal
      concentrations of ROS triggered an arrest with some morphological similarities to
      cellular senescence. Different from a classical senescent arrest in G(1), the ROS
      induced arrest was predominantly in the G(2) phase of the cell cycle, and its
      establishment depended at least in part on an intact Chk1-dependent checkpoint.
      Chk1 remained phosphorylated only during the repair of double strand DNA breaks,
      after which Chk1 was inactivated, the G(2) arrest was suppressed, and some cells
      recovered their ability to proliferate. Inhibition of Chk1 by an RNAi approach
      resulted in an increase in cell death in p53-null cells, showing that the Chk1
      dependent G(2) checkpoint protected cells that lacked a functional p53 pathway
      from oxidative stress. It has been proposed that the induction of a senescent
      like phenotype by antineoplastic agents can contribute therapeutic efficacy. Our
      results indicate that oxidative stress-induced growth arrest of p53-null tumor
      cells cannot be equated with effective therapy owing to its reversibility and
      supports the concept that targeting Chk1 may enhance the effects of DNA-damaging
      agents on cancer progression in such tumors.

PMID- 16652145
TI  - Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to
      bone marrow endothelial cells.
AB  - Using a validated tetracycline (tet)-regulated MCF7-founder (MCF7F) expression
      system to modulate expression of CD44 standard form (CD44s), we report the
      functional importance of CD44s and that of a novel transcriptional target of
      hyaluronan (HA)/CD44s signaling, EMS1/cortactin, in underpinning breast cancer
      metastasis. In functional experiments, tet-regulated induction of CD44s
      potentiated the migration and invasion of MCF7F cells through HA-supplemented
      Matrigel. EMS1/cortactin was identified by expression profiling as a novel
      transcriptional target of HA/CD44 signaling, an association validated by
      quantitative PCR and immunoblotting experiments in a range of breast cancer cell
      lines. The mechanistic basis underpinning CD44-promoted transcription of
      EMS1/cortactin was shown to be dependent upon a NFkappaB mechanism, since
      pharmacological inhibition of IkappaKinase-2 or suppression of p65 Rel A
      expression attenuated CD44-induced increases in cortactin mRNA transcript levels.
      Overexpression of a c-myc tagged murine cortactin construct in the weakly
      invasive, CD44-deficient MCF7F and T47D cells potentiated their invasion.
      Furthermore, the functional importance of cortactin to CD44s-promoted metastasis
      was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F
      B5 and MDA-MB-231 breast cancer cells using RNAi, which was shown to result in
      attenuated CD44-promoted invasion and CD44-promoted adhesion to bone marrow
      endothelial cells (BMECs).

PMID- 16652146
TI  - Sustained expression of Mect1-Maml2 is essential for tumor cell growth in
      salivary gland cancers carrying the t(11;19) translocation.
AB  - Mucoepidermoid (MEC) salivary gland tumors arise from a t(11;19) rearrangement
      which generates a fusion oncogene, Mect1-Maml2, that functions to activate CREB
      responsive target genes. To determine if sustained expression of Mect1-Maml2 is
      required for tumor cell growth, we first showed that ectopic expression of Mect1
      Maml2 in rat epithelial RK3E cells is tumorigenic in vivo in nude mice and that
      excised xenografts continue to express the fusion oncogene. We then generated a
      hairpin RNAi vector that selectively suppressed the fusion peptide and showed
      that ectopic expression in either parotid or pulmonary MEC tumor cell lines
      containing the t(11;19) rearrangement resulted in at least 90% colony growth
      inhibition. In contrast, single nucleotide changes within this RNAi sequence
      abolished the ability to suppress Mect1-Maml2 protein and abolished all growth
      inhibition of these MEC tumor lines. In addition, the RNAi-specific vector had no
      effect on colony growth of non-MEC tumors including a lung tumor or two other
      salivary gland cell lines that do not express Mect1-Maml2. We also generated a
      mutant Mect1-Maml2 expression plasmid that carried silent nucleotide changes
      within the RNAi target sequence and observed that co-transfection of this mutant,
      but not wild-type Mect1-Maml2, could partially rescue RNAi growth inhibition in
      the MEC tumor line. The recent detection of acquired fusion oncogenes in
      epithelial solid tumors has suggested new possibilities for the diagnosis and
      therapy of these cancers. Our data show that the 'gain-of-function' activity from
      aberrant Mect1-Maml2 expression is a candidate therapeutic target for this group
      of malignant salivary gland tumors.

PMID- 16652147
TI  - RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription.
AB  - RUNX1 (AML1) is a gene that is frequently disrupted by chromosomal translocations
      in acute leukemia. Like its Drosophila homolog Runt, RUNX1 both activates and
      represses transcription. Both Runt and RUNX1 are required for gene silencing
      during development and a central domain of RUNX1, termed repression domain 2
      (RD2), was defined as being required for transcriptional repression and for the
      silencing of CD4 during T-cell maturation in thymic organ cultures. Although
      transcriptional co-repressors are known to contact other repression domains in
      RUNX1, the factors that bind to RD2 had not been defined. Therefore, we tested
      whether RD2 contacts histone-modifying enzymes that may mediate both repression
      and gene silencing. We found that RD2 contacts SUV39H1, a histone
      methyltransferase, via two motifs and that endogenous Suv39h1 associates with a
      Runx1-regulated repression element in murine erythroleukemia cells. In addition,
      one of these SUV39H1-binding motifs is also sufficient for binding to histone
      deacetylases 1 and 3, and both of these domains are required for full RUNX1
      mediated transcriptional repression. The association between RUNX1, histone
      deacetylases and SUV39H1 provides a molecular mechanism for repression and
      possibly gene silencing mediated by RUNX1.

PMID- 16652148
TI  - Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in
      mesothelioma cells and negatively regulates FAK.
AB  - The neurofibromatosis type 2 NF2 gene product, merlin, is a tumor suppressor
      frequently inactivated in malignant mesothelioma (MM). To investigate a possible
      correlation between merlin inactivation and MM invasiveness, we restored merlin
      expression in NF2-deficient MM cells. Re-expression of merlin markedly inhibited
      cell motility, spreading and invasiveness, properties connected with the
      malignant phenotype of MM cells. To test directly whether merlin inactivation
      promotes invasion in a nonmalignant system, we used small interfering RNA to
      silence Nf2 in mouse embryonic fibroblasts (MEFs) and found that downregulation
      of merlin resulted in enhanced cell spreading and invasion. To delineate
      signaling events connected with this phenotype, we investigated the effect of
      merlin expression on focal adhesion kinase (FAK), a key component of cellular
      pathways affecting migration and invasion. Expression of merlin attenuated FAK
      phosphorylation at the critical phosphorylation site Tyr397 and disrupted the
      interaction of FAK with its binding partners Src and p85, the regulatory subunit
      of phosphatidylinositol-3-kinase. In addition, NF2-null MM cells stably
      overexpressing FAK showed increased invasiveness, which decreased significantly
      when merlin expression was restored. Collectively, these findings suggest that
      merlin inactivation is a critical step in MM pathogenesis and is related, at
      least in part, with upregulation of FAK activity.

PMID- 16652149
TI  - Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by
      RhoA kinase signaling and inhibited by neutral endopeptidase.
AB  - The neuropeptides bombesin and endothelin-1 stimulate prostate cancer (PC) cell
      migration and invasion (J Clin Invest, 2000; 106: 1399-1407). The intracellular
      signaling pathways that direct this cell movement are not well delineated. The
      monomeric GTPase RhoA is required for migration in several cell types including
      neutrophils, monocytes and fibroblasts. We demonstrate that bombesin-stimulated
      PC cell migration occurs via the heterotrimeric G-protein-coupled receptors (G
      protein) G alpha 13 subunit leading to activation of RhoA, and Rho-associated
      coiled-coil forming protein kinase (ROCK). Using siRNA to suppress expression of
      the three known G-protein alpha-subunit-associated RhoA guanine nucleotide
      exchange factors (GEFs), we also show that two of these RhoA GEFs, PDZ-RhoGEF and
      leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non
      redundant manner in PC cells. We next show that focal adhesion kinase, which
      activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated RhoA
      activation. Neutral endopeptidase (NEP) is expressed on normal prostate
      epithelium whereas loss of NEP expression contributes to PC progression. We also
      demonstrate that NEP inhibits neuropeptide activation of RhoA. Together, these
      results establish a contiguous signaling pathway from the bombesin receptor to
      ROCK in PC cells, and they implicate NEP as a major regulator of neuropeptide
      stimulated RhoA in these cells. This work also identifies members of this
      signaling pathway as potential targets for rational pharmacologic manipulation of
      neuropeptide-stimulated migration of PC cells.

PMID- 16652150
TI  - Identification of expressed genes characterizing long-term survival in malignant
      glioma patients.
AB  - Better understanding of the underlying biology of malignant gliomas is critical
      for the development of early detection strategies and new therapeutics. This
      study aimed to define genes associated with survival. We investigated whether
      genes coupled with a class prediction model could be used to define subgroups of
      high-grade gliomas in a more objective manner than standard pathology. RNAs from
      29 malignant gliomas were analysed using Agilent microarrays. We identified 21
      genes whose expression was most strongly and consistently related to patient
      survival based on univariate proportional hazards models. In six out of 10 genes,
      changes in gene expression were validated by quantitative real-time PCR. After
      adjusting for clinical covariates based on a multivariate analysis, we finally
      obtained a statistical significance level for DDR1 (discoidin domain receptor
      family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated
      kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed
      that DDR1 protein expression was also correlated to the prognosis of glioma
      patients detected by immunohistochemical staining. Furthermore, we analysed the
      efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA
      synthesis in glioma cell lines. Cell proliferation and invasion were
      significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel
      molecular target of therapy as well as an important predictive marker for
      survival in patients with glioma. Our method was effective at classifying high
      grade gliomas objectively, and provided a more accurate predictor of prognosis
      than histological grading.

PMID- 16652151
TI  - Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head
      to-head Ets binding sites present in the promoter.
AB  - Regulation of the gene expression of Stromelysin-1 (matrix metalloproteinase-3),
      a member of the matrix metalloproteinase family, is critical for tissue
      homeostasis. The Stromelysin-1 promoter is known to be transactivated by Ets
      proteins through palindromic head-to-head Ets binding sites (EBS), an unusual
      configuration among metalloproteinase promoters. Patterns of increased co
      expression of Stromelysin-1 and Ets-1 genes have been observed in pathological
      processes such as rheumatoid arthritis, glomerulonephritis and tumor invasion. In
      this context, we show in a synovial fibroblastic model cell line (HIG-82), which
      is able to co-express Stromelysin-1 and Ets-1, that the EBS palindrome is
      essential for the expression of Stromelysin-1. More precisely, using
      electrophoretic mobility shift assays, DNA affinity purification and chromatin
      immunoprecipitation, we demonstrate that endogenous Ets-1, but not Ets-2, is
      present on this palindrome. The use of a dominant-negative form of Ets-1 and the
      decrease of Ets-1 amount either by fumagillin, an antiangiogenic compound, or by
      short interfering RNA show that the activation rate of the promoter and the
      expression of Stromelysin-1 correlate with the level of endogenous Ets-1. Thus,
      it is the first demonstration, using this cellular model, that endogenously
      expressed Ets-1 is actually a main activator of the Stromelysin-1 promoter
      through its effective binding to the EBS palindrome.

PMID- 16652152
TI  - Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of
      tumour cell invasion: a link to integrin function.
AB  - Cancer cells can invade three-dimensional matrices by distinct mechanisms,
      recently defined by their dependence on extracellular proteases, including matrix
      metalloproteinases. Upon treatment with protease inhibitors, some tumour cells
      undergo a 'mesenchymal to amoeboid' transition that allows invasion in the
      absence of pericellular proteolysis and matrix degradation. We show here that in
      HT1080 cells, this transition is associated with weakened integrin-dependent
      adhesion, consistently reduced cell surface expression of the alpha2beta1
      integrin collagen receptor and impaired signalling downstream, as judged by
      reduced autophosphorylation of focal adhesion kinase (FAK). On examining cancer
      cells that use defined invasion strategies, we show that distinct from
      mesenchymal invasion, amoeboid invasion is independent of intracellular calpain 2
      proteolytic activity that is usually needed for turnover of integrin-linked
      adhesions during two-dimensional planar migration. Moreover, an inhibitor of
      Rho/ROCK signalling, which specifically impairs amoeboid-like invasion, restores
      cell surface expression of alpha2beta1 integrin, downstream FAK
      autophosphorylation and calpain 2 sensitivity--features of mesenchymal invasion.
      These findings link weakened integrin function to a lack of requirement for
      calpain 2-mediated integrin adhesion turnover during amoeboid invasion. In
      keeping with the need for integrin adhesion turnover, mesenchymal invasion is
      uniquely sensitive to Src inhibitors. Thus, the need for a major pathway that
      controls integrin adhesion turnover defines and distinguishes cancer cell
      invasion strategies.

PMID- 16652153
TI  - DNA-binding independent cell death from a minimal proapoptotic region of E2F-1.
AB  - The ability to induce cell cycle progression while evading cell death is a
      defining characteristic of cancer. Deregulation of E2F is a common event in most
      human cancers. Paradoxically, this can lead to both cell cycle progression and
      apoptosis. Although the way in which E2F causes cell cycle progression is well
      characterized, the pathways by which E2F induces cell death are less well
      defined. Many of the known mechanisms through which E2F induces apoptosis occur
      through regulation of E2F target genes. However, mutants of E2F-1 that lack the
      transactivation domain are still able to induce cell death. To further
      investigate this activity, we refined a transactivation independent mutant to
      identify a minimal apoptotic domain. This revealed that only 75 amino acids from
      within the DNA-binding domain of E2F-1 is sufficient for cell death and that this
      activity is also present in the DNA-binding domains of E2F-2 and E2F-3. However,
      analysis of this domain from E2F-1 revealed it does not bind DNA and is
      consequently unable to transactivate, repress or de-repress E2F target genes.
      This provocative observation therefore defines a potential new mechanism of death
      from E2F and opens up new opportunities for inducing cell death in tumours for
      therapeutic gain.

PMID- 16652154
TI  - Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin:
      in vitro and in vivo studies in acute leukemia.
AB  - The telomerase complex is responsible for telomere maintenance and represents a
      promising neoplasia therapeutic target. Recently, we have demonstrated that
      treatment with a G-quadruplex-interactive agent, telomestatin reproducibly
      inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines. In the
      present study, we investigated the mechanisms of apoptosis induced by telomerase
      inhibition in acute leukemia. We have found the activation of caspase-3 and poly
      (ADP-ribose) polymerase in telomestatin-treated U937 cells (PD20) and dominant
      negative DN-hTERT-expressing U937 cells (PD25). Activation of p38 mitogen
      activated protein (MAP) kinase and MKK3/6 was also found in telomestatin-treated
      U937 cells (PD20) and dominant-negative DN-hTERT-expressing U937 cells (PD25);
      however, activation of JNK and ASK1 was not detected in these cells. To examine
      the effect of p38 MAP kinase inhibition on growth properties and apoptosis in
      telomerase-inhibited cells, we cultured DN-hTERT-expressing U937 cells with or
      without SB203580. Dominant-negative-hTERT-expressing U937 cells stopped
      proliferation on PD25; however, a significant increase in growth rate was
      observed in the presence of SB203580. Treatment of SB203580 also reduced the
      induction of apoptosis in DN-hTERT-expressing U937 cells (PD25). These results
      suggest that p38 MAP kinase has a critical role for the induction of apoptosis in
      telomerase-inhibited leukemia cells. Further, we evaluated the effect of
      telomestatin on the growth of U937 cells in xenograft mouse model. Systemic
      intraperitoneal administration of telomestatin in U937 xenografts decreased tumor
      telomerase levels and reduced tumor volumes. Tumor tissue from telomestatin
      treated animals exhibited marked apoptosis. None of the mice treated with
      telomestatin displayed any signs of toxicity. Taken together, these results lay
      the foundations for a program of drug development to achieve the dual aims of
      efficacy and selectivity in vivo.

PMID- 16652155
TI  - Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4.
AB  - The four members of the ErbB family of receptor tyrosine kinases are involved in
      development and tumorigenesis of the mammary gland. Whereas the epidermal growth
      factor receptor, ErbB2 and ErbB3 are positively associated with various cancers,
      clinical studies of ErbB4 in breast cancer are contradictory. Results from tissue
      culture analyses and some clinical studies suggested that ErbB4 is either a tumor
      suppressor or is a negative regulator of ErbB2-driven tumors. Neu-Cre
      ErbB4(flox/null) mice in which ErbB4 was inactivated by Cre-lox-mediated
      recombination in the mammary gland developed MMTV-Neu-driven mammary tumors with
      a similar latency period to mice with one or two wild-type ErbB4 alleles.
      Moreover, there was no difference in the histologies of tumors that developed,
      nor in the propensity to form lung metastases. Taken together these results
      suggest that ErbB4 is not a potent, highly penetrant tumor suppressor, nor is it
      a factor in Neu-mediated tumorigenesis in this model.

PMID- 16652156
TI  - Functional connection between p53 and caspase-2 is essential for apoptosis
      induced by DNA damage.
AB  - Recent findings have established caspase-2 as an important apical regulator in
      apoptotic pathways leading from DNA damage to release of mitochondrial cytochrome
      c and subsequent activation of effector caspases. Yet, the molecular map
      connecting the embarking stimuli of genotoxic stress with caspase-2 activation
      remains to be elucidated. Here, we address the question of potential caspase-2
      regulators by examining 5-fluorouracil (5-FU)-induced apoptosis in wild-type and
      p53-deficient human colon carcinoma cells. Apoptosis was observed only in
      p53(+/+) cells and was preceded by caspase-2 activation. Hence, although no
      direct interaction between p53 and caspase-2 was observed in the cell system
      used, our data clearly demonstrate that a functional connection between these two
      proteins is essential for initiation of the 5-FU-induced apoptotic process.
      Proposed mediators of caspase-2 activation include PIDDosome complex proteins
      PIDD and RAIDD. Surprisingly, the presence of a complex encompassing at least
      RAIDD, PIDD and caspase-2 was verified in both p53(+/+) and p53(-/-) cells, also
      in the absence of 5-FU treatment. Thus, our results confirm the participation of
      PIDD and RAIDD in PIDDosome complex formation but question their role as sole
      mediators of caspase-2 activation. This assumption was further supported by siRNA
      transfections targeting PIDD or RAIDD. In conclusion, our findings support the
      hypothesis of p53 as an upstream regulator of caspase activity and provide data
      concerning caspase-2 processing mechanisms. As suppression of caspase-2
      expression in 5-FU-treated cells also affects the level of the p53 protein,
      possibilities of a reciprocal interaction between these proteins are discussed.

PMID- 16652157
TI  - The LIM-only protein FHL2 is a negative regulator of E4F1.
AB  - The E1A-targeted transcription factor E4F1 is a key player in the control of
      mammalian embryonic and somatic cell proliferation and survival. Mouse embryos
      lacking E4F die at an early developmental stage, whereas enforced expression of
      E4F1 in various cell lines inhibits cell cycle progression. E4F1
      antiproliferative effects have been shown to depend on its capacity to repress
      transcription and to interact with pRb and p53. Here we show that full-length
      E4F1 protein (p120(E4F1)) but not its E1A-activated and truncated form
      (p50(E4F1)), interacts directly in vitro and in vivo with the LIM-only protein
      FHL2, the product of the p53-responsive gene FHL2/DRAL (downregulated in
      rhabdomyosarcoma Lim protein). This E4F1-FHL2 association occurs in the nuclear
      compartment and inhibits the capacity of E4F1 to block cell proliferation.
      Consistent with this effect, ectopic expression of FHL2 inhibits E4F1 repressive
      effects on transcription and correlates with a reduction of nuclear E4F1-p53
      complexes. Overall, these results suggest that FHL2/DRAL is an inhibitor of E4F1
      activity. Finally, we show that endogenous E4F1-FHL2 complexes form in U2OS cells
      upon UV-light-induced nuclear accumulation of FHL2.

PMID- 16652158
TI  - A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished
      promoter activity and increased risk of non-small cell lung cancer.
AB  - X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision
      repair and cells lacking its activity are hypersensitive to DNA damage. Recently,
      we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region
      (UTR) was significantly associated with the risk of developing esophageal
      squamous-cell carcinoma. Computer analysis predicted that this SNP was in the
      core of Sp1-binding motif, which suggested its functional significance. Gel shift
      and super shift assays confirmed that -77T>C polymorphic site in the XRCC1
      promoter was within the Sp1-binding motif and the T>C substitution greatly
      enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated
      that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced
      transcriptional activity. The association between -77T>C and three other amino
      acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was
      examined in 1024 patients and 1118 controls and the results showed that only the 
      77T>C polymorphism was significantly associated with an increased risk of
      developing lung cancer. Multivariate logistic regression analysis found that an
      increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes
      (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001)
      and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21)
      than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results
      showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer
      development owing to the decreased transcriptional activity of C-allele
      containing promoter with higher affinity to Sp1 binding.

PMID- 16652159
TI  - DNp73alpha protects myogenic cells from apoptosis.
AB  - The P73 gene is transcribed from two promoters, P1 and P2, that direct the
      expression of multiple transactivation competent (TA) and dominant negative (DN)
      isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis
      in response to DNA damage and are involved in developmental processes. P73 mRNA
      levels increase and the P1p73 promoter is upregulated during myogenic
      differentiation of C2C12 skeletal muscle satellite cells. The DNp73 proteins act
      as trans-repressors of p53- and p73-dependent transcription, and possess both
      antiapoptotic and pro-proliferative potential. Here, we show that DNp73alpha is
      expressed in proliferating C2C12 myoblasts, rapidly accumulates in
      differentiating myocytes and remains elevated in C2C12 myotubes. By combining
      transactivation assays and chromatin immunoprecipitation analysis, we could show
      that the upregulation of the P2p73 promoter during myogenic differentiation is
      mediated by the coordinated recruitment and activity of MyoD and p53/p73.
      Abrogation of DNp73 expression by specific siRNA led to a strong potentiation of
      the spontaneous apoptosis of C2C12 myoblasts induced to differentiate. Finally,
      unlike TAp73 that contributes to DNA damage-induced apoptosis of myotubes,
      endogenous DNp73 mediates the relative resistance of differentiated myotubes to
      DNA damage. Altogether, our findings identify DNp73alpha as an important target
      in designing strategies aimed at the potentiation of the regenerative potential
      of skeletal satellite cells.

PMID- 16652161
TI  - Nephrologists Sans Frontieres: chronic kidney disease in Japan.

PMID- 16652162
TI  - Nephrology at Washington University School of Medicine: my early days.

PMID- 16652163
TI  - Infected right atrial thrombus associated with a tunneled hemodialysis catheter.

PMID- 16652164
TI  - The arrow of bioimpedance.
AB  - The value of bioimpedance in hemodialysis remains under debate. However, when
      appropriately used, bioimpedance can provide measures of body hydration
      characterized by a small error, a high sensitivity to changes in water volume,
      and, above all, a linear relationship over a wide range of volume changes. These
      features make it very useful to measure body hydration in hemodialysis patients.

PMID- 16652166
TI  - Management of hyperuricemia-associated endothelial dysfunction: from the bench to
      the clinical practice.

PMID- 16652167
TI  - Purinergic receptors activating rapid intracellular Ca increases in microglia.
AB  - We provide both molecular and pharmacological evidence that the metabotropic,
      purinergic, P2Y(6), P2Y(12) and P2Y(13) receptors and the ionotropic P2X(4)
      receptor contribute strongly to the rapid calcium response caused by ATP and its
      analogues in mouse microglia. Real-time PCR demonstrates that the most prevalent
      P2 receptor in microglia is P2Y(6) followed, in order, by P2X(4), P2Y(12), and
      P2X(7) = P2Y(13). Only very small quantities of mRNA for P2Y(1), P2Y(2), P2Y(4),
      P2Y(14), P2X(3) and P2X(5) were found. Dose-response curves of the rapid calcium
      response gave a potency order of: 2MeSADP>ADP=UDP=IDP=UTP>ATP>BzATP, whereas A2P4
      had little effect. Pertussis toxin partially blocked responses to 2MeSADP, ADP
      and UDP. The P2X(4) antagonist suramin, but not PPADS, significantly blocked
      responses to ATP. These data indicate that P2Y(6), P2Y(12), P2Y(13) and P2X
      receptors mediate much of the rapid calcium responses and shape changes in
      microglia to low concentrations of ATP, presumably at least partly because ATP is
      rapidly hydrolyzed to ADP. Expression of P2Y(6), P2Y(12) and P2Y(13) receptors
      appears to be largely glial in the brain, so that peripheral immune cells and CNS
      microglia share these receptors. Thus, purinergic, metabotropic, P2Y(6), P2Y(12),
      P2Y(13) and P2X(4) receptors might share a role in the activation and recruitment
      of microglia in the brain and spinal cord by widely varying stimuli that cause
      the release of ATP, including infection, injury and degeneration in the CNS, and
      peripheral tissue injury and inflammation which is signaled via nerve signaling
      to the spinal cord.

PMID- 16652168
TI  - Early events in node of Ranvier formation during myelination and remyelination in
      the PNS.
AB  - Action potential conduction velocity increases dramatically during early
      development as axons become myelinated. Integral to this process is the
      clustering of voltage-gated Na(+) (Nav) channels at regularly spaced gaps in the
      myelin sheath called nodes of Ranvier. We show here that some aspects of
      peripheral node of Ranvier formation are distinct from node formation in the CNS.
      For example, at CNS nodes, Nav1.2 channels are detected first, but are then
      replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels
      are detected at newly forming nodes. By contrast, the earliest Nav-channel
      clusters detected during developmental myelination in the PNS have Nav1.6.
      Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we
      show that accumulation of the cell adhesion molecule neurofascin always precedes
      Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186)
      accumulates first, but occasionally paranodal neurofascin is detected first. We
      suggest there is heterogeneity in the events leading to Nav channel clustering,
      indicating that multiple mechanisms might contribute to node of Ranvier formation
      in the PNS.

PMID- 16652169
TI  - Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB
      pathways.
AB  - Forkhead box (Fox)/winged-helix transcription factors regulate multiple aspects
      of immune responsiveness and Foxp3 is recognized as an essential functional
      marker of regulatory T cells. Herein we describe downstream signaling pathways
      targeted by Foxp3 that may negatively impact retroviral pathogenesis.
      Overexpression of Foxp3 in HEK 293T and purified CD4+ T cells resulted in a dose
      dependent and time-dependent decrease in basal levels of nuclear factor-kappaB
      (NF-kappaB) activation. Deletion of the carboxyl-terminal forkhead (FKH) domain,
      critical for nuclear localization and DNA-binding activity, abrogated the ability
      of Foxp3 to suppress NF-kappaB activity in HEK 293T cells, but not in Jurkat or
      primary human CD4+ T cells. We further demonstrate that Foxp3 suppressed the
      transcription of two human retroviral promoters (HIV-1 and human T cell
      lymphotropic virus type I [HTLV-I]) utilizing NF-kappaB-dependent and NF-kappaB
      independent mechanisms. Examination of the latter identified the cAMP-responsive
      element binding protein (CREB) pathway as a target of Foxp3. Finally, comparison
      of the percent Foxp3+CD4+CD25+ T cells to the HTLV-I proviral load in HTLV-I
      infected asymptomatic carriers and patients with HTLV-I-associated
      myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is
      associated with low proviral load and absence of disease. These results suggest
      an expanded role for Foxp3 in regulating NF-kappaB- and CREB-dependent cellular
      and viral gene expression.

PMID- 16652170
TI  - RNA interference analysis of Legionella in Drosophila cells: exploitation of
      early secretory apparatus dynamics.
AB  - Legionella pneumophila translocates multiple bacterial effector proteins into
      host cells to direct formation of a replication vacuole for the bacterium. The
      emerging consensus is that formation of this compartment involves recruitment of
      membrane material that traffics between the endoplasmic reticulum (ER) and Golgi.
      To investigate this model, a targeted approach was used to knock down expression
      of proteins involved in membrane trafficking, using RNA interference in
      Drosophila cells. Surprisingly, few single knockdowns of ER-Golgi transport
      proteins decreased L. pneumophila replication. By analyzing double-stranded RNAs
      in pairs, combinations were identified that together caused defects in
      intracellular replication, consistent with the model that membrane traffic
      funnels into the replication vacuole from multiple sources. In particular,
      simultaneous depletion of the intermediate compartment and Golgi-tethering factor
      transport protein particle together with the ER SNARE protein Sec22 reduced
      replication efficiency, indicating that introduction of lesions at distinct sites
      in the secretory system reduces replication efficiency. In contrast to knockdowns
      in secretory traffic, which required multiple simultaneous hits, knockdown of
      single cytosolic components of ER-associated degradation, including Cdc48/p97 and
      associated cofactors, was sufficient to inhibit intracellular replication. The
      requirement for the Cdc48/p97 complex was conserved in mammalian cells, in which
      replication vacuoles showed intense recruitment of ubiquitinated proteins, the
      preferred substrates of Cdc48/p97. This complex promoted dislocation of both
      ubiquitinated proteins and bacterial effectors from the replication vacuole,
      consistent with the model that maintenance of high-level replication requires
      surveillance of the vacuole surface. This work demonstrates that L. pneumophila
      has the ability to gain access to multiple sites in the secretory system and
      provides the first evidence for a role of the Cdc48/p97 complex in promoting
      intracellular replication of pathogens and maintenance of replication vacuoles.

PMID- 16652172
TI  - The Acetobacteraceae: extending the spectrum of human pathogens.

PMID- 16652171
TI  - A drug-sensitive genetic network masks fungi from the immune system.
AB  - Fungal pathogens can be recognized by the immune system via their beta-glucan, a
      potent proinflammatory molecule that is present at high levels but is
      predominantly buried beneath a mannoprotein coat and invisible to the host. To
      investigate the nature and significance of "masking" this molecule, we
      characterized the mechanism of masking and consequences of unmasking for immune
      recognition. We found that the underlying beta-glucan in the cell wall of Candida
      albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin,
      causing the exposed fungi to elicit a stronger immune response. Using a library
      of bakers' yeast (Saccharomyces cerevisiae) mutants, we uncovered a conserved
      genetic network that is required for concealing beta-glucan from the immune
      system and limiting the host response. Perturbation of parts of this network in
      the pathogen C. albicans caused unmasking of its beta-glucan, leading to
      increased beta-glucan receptor-dependent elicitation of key proinflammatory
      cytokines from primary mouse macrophages. By creating an anti-inflammatory
      barrier to mask beta-glucan, opportunistic fungi may promote commensal
      colonization and have an increased propensity for causing disease. Targeting the
      widely conserved gene network required for creating and maintaining this barrier
      may lead to novel broad-spectrum antimycotics.

PMID- 16652173
TI  - PITANSEMA-MAS, a solid-state NMR method to measure heteronuclear dipolar
      couplings under MAS.
AB  - A 2D NMR method is presented for the measurement of the dipole-dipole interaction
      between a proton and a low-frequency nuclear spin species in the solid state
      under the magic angle spinning. It employs the time averaged nutation concept to
      dramatically reduce the required radio frequency (rf) power on the low gamma
      nuclear channel and spin exchange at the magic angle is used to suppress (1)H
      (1)H dipolar interactions and chemical shifts. The flexibility in choosing the
      spinning speed, rf power and the scaling factor of the pulse sequence are of
      considerable importance for the structural studies of biological solids. The
      performance of the pulse sequence has been numerically and experimentally
      demonstrated on several solids.

PMID- 16652174
TI  - Active transport: a new chemical separation method?

PMID- 16652175
TI  - On-chip pressure injection for integration of infrared-mediated DNA amplification
      with electrophoretic separation.
AB  - Poly(dimethylsiloxane) (PDMS) membrane valves were utilized for diaphragm pumping
      on a PDMS-glass hybrid microdevice in order to couple infrared-mediated DNA
      amplification with electrophoretic separation of the products in a single device.
      Specific amplification products created during non-contact, infrared (IR)
      mediated polymerase chain reaction (PCR) were injected via chip-based diaphragm
      pumping into an electrophoretic separation channel. Channel dimensions were
      designed for injection plug shaping via preferential flow paths, which aided in
      minimizing the plug widths. Unbiased injection of sample could be achieved in as
      little as 190 ms, decreasing the time required with electrokinetic injection by
      two orders of magnitude. Additionally, sample stacking was promoted using laminar
      or biased-laminar loading to co-inject either water or low ionic strength DNA
      marker solution along with the PCR-amplified sample. Complete baseline resolution
      (Res = 2.11) of the 80- and 102-bp fragments of pUC-18 DNA marker solution was
      achieved, with partially resolved 257- and 267-bp fragments (Res = 0.56), in a
      separation channel having an effective length of only 3.0 cm. This resolution was
      deemed adequate for many PCR amplicon separations, with the added advantage of
      short separation time-typically complete in <120 s. Decreasing the amount of
      glass surrounding the PCR chamber reduced the DNA amplification time, yielding a
      further enhancement in analysis speed, with heating and cooling rates as high as
      13.4 and -6.4 degrees C s(-1), respectively. With the time requirements greatly
      reduced for each step, it was possible to seamlessly couple IR-mediated
      amplification, sample injection, and separation/detection of a 278-bp fragment
      from the invA gene of <1000 starting copies of Salmonella typhimurium DNA in
      approximately 12 min on a single device, representing the fastest PCR-ME
      integration achieved to date.

PMID- 16652176
TI  - A microsystem for sensing and patterning oxidative microgradients during cell
      culture.
AB  - We present the design, modeling, fabrication and testing of a microsystem for the
      electrolytic patterning and sensing of oxidative microgradients within 1 x 1 mm2
      area during cell culture. The system employs an array of microfabricated
      electrodes (3-40 microm in width) embedded in gas-permeable microchannels to
      generate precise doses of dissolved oxygen (ranging from 10 fmol O2 mm(-2) s(-1)
      to 100 nmol O2 mm(-2) s(-1)) via electrolysis. The microgradients generated by
      different microelectrodes in the array can be superimposed to pattern multi
      dimensional oxygen profiles not possible with other methods. We demonstrate the
      patterning, sensing and quantification of dissolved oxygen microgradients in the
      0 to 40% dO2 range using this microsystem. Reactive oxygen species generation and
      dosing is also quantified. Lastly, we demonstrate how the microtechnology enables
      new types of experiments in three different cell culture models: localized
      hyperoxia-induced apoptosis in C2C12 myoblasts, dynamic aerotaxis assays of
      Bacillus subtilis, and studies of calcium release in an ischemia/re-oxygenation
      myoblast model.

PMID- 16652177
TI  - Development and multiplexed control of latching pneumatic valves using
      microfluidic logical structures.
AB  - Novel latching microfluidic valve structures are developed, characterized, and
      controlled independently using an on-chip pneumatic demultiplexer. These
      structures are based on pneumatic monolithic membrane valves and depend upon
      their normally-closed nature. Latching valves consisting of both three- and four
      valve circuits are demonstrated. Vacuum or pressure pulses as short as 120 ms are
      adequate to hold these latching valves open or closed for several minutes. In
      addition, an on-chip demultiplexer is demonstrated that requires only n pneumatic
      inputs to control 2(n-1) independent latching valves. These structures can reduce
      the size, power consumption, and cost of microfluidic analysis devices by
      decreasing the number of off-chip controllers. Since these valve assemblies can
      form the standard logic gates familiar in electronic circuit design, they should
      be useful in developing complex pneumatic circuits.

PMID- 16652178
TI  - A nanofabricated planar aperture as a mimic of the nerve-muscle contact during
      synaptogenesis.
AB  - The release of synaptogenic factors by the nerve terminal plays a central role in
      the aggregation of neurotransmitter receptors at the postsynaptic membrane, a
      precisely timed and localized process that is essential for the correct formation
      and functioning of the synapse. This process has been difficult to re-capitulate
      in cell culture because present cell stimulation methods do not have sufficient
      spatiotemporal control of the delivery of soluble signals. We cultured myotubes
      atop nanofabricated planar apertures (2-8 microm diameter) to focally stimulate
      the muscle cell membrane with neural agrin, a synaptogenic factor released by
      motor neurons during development. Focal agrin delivery through the apertures
      after myotube fusion results in local aggregation of acetylcholine receptors
      (AChRs) in the vicinity of the apertures, a process reminiscent of AChR
      clustering at innervation sites. Since the apertures are spatially organized in
      microarrays, multiple experiments can be run in parallel on one device. The
      technique has wide applicability in cell-cell communication studies and cell
      based bioassays.

PMID- 16652179
TI  - A method for dynamic system characterization using hydraulic series resistance.
AB  - The pressure required to drive flow through a microfluidic device is an important
      characteristic of that device. We present a method to measure the flow rate
      through microfluidic components and systems, including micropumps and
      microvalves. The measurement platform is composed of two pressure sensors and a
      glass tube, which provides series resistance. The principle of the measurement is
      the fluid dynamical equivalent of Ohm's law, which defines the relationship
      between current, resistance, and voltage that are analogues to flow rate,
      hydraulic resistance, and pressure drop, respectively. Once the series resistance
      is known, it is possible to compute the flow rate through a device based on
      pressure alone. In addition, the dynamic system characteristics of the device
      resistance and capacitance-can be computed. The benefits of this method are its
      simple configuration, capability of measuring flow rate accurately from the more
      easily measured pressure, and the ability to predict the dynamic response of
      microfluidic devices.

PMID- 16652180
TI  - Characterization of a microscale cyclical electrical field flow fractionation
      system.
AB  - A microscale cyclical electrical field flow fractionation (CyElFFF) channel is
      characterized with regard to the effect of various operating parameters and
      comparison made to recent theoretical developments. Challenges associated with
      various operating conditions are reported along with some of the optimized
      operating parameters. The effect of retention wall choice, an offset voltage,
      relaxation steps, and flow rates, along with the basic operating parameters of
      voltage, frequency, and electrophoretic mobility are reported. Retention of
      polystyrene nanoparticle standards is accomplished and the first separations
      using this technique in a microscale system are also demonstrated. Relaxation
      steps and offset voltages are found to be effective in eliminating early peaks
      and in improving plate heights. Plate heights were also found to decrease with
      increasing flow rates, which is the opposite of the behavior seen in most
      existing chromatographic systems. The experimental results are compared to the
      analytical and empirical models of CyElFFF and found to be compatible.
      Suggestions are made for improving the separation and analysis methods used with
      CyElFFF.

PMID- 16652181
TI  - Critical particle size for fractionation by deterministic lateral displacement.
AB  - The fractionation of small particles in a liquid based on their size in a
      micropost array by deterministic lateral displacement was recently demonstrated
      with unprecedented resolution (L. R. Huang, E. C. Cox, R. H. Austin and J. C.
      Sturm, Science, 2004, 304, 987-990, ). In this paper, we present a model of how
      the critical particle size for fractionation depends on the micropost geometry,
      depending specifically on the gap between posts, the offset of posts in one row
      with respect to another, and whether the fluid is driven by hydrodynamics or by
      electroosmosis. In general the critical particle diameter is much smaller than
      the gap, which prevents clogging. The model is supported by data with particles
      from 2.3 to 22 microm.

PMID- 16652182
TI  - An effervescent reaction micropump for portable microfluidic systems.
AB  - A water-activated, effervescent reaction was used to transport fluid in a
      controllable manner on a portable microfluidic device. The reaction between
      sodium bicarbonate and an organic acid, tartaric acid and/or benzoic acid, was
      modeled to analyze methods of controlling the generation of carbon-dioxide gas
      for the purposes of pumping fluids. Integration and testing of the effervescent
      reaction pump in a microfluidic device was made possible by using elastomeric
      polymers as both photopolymerizable septa and removable lids. These materials
      combined to enable facile access to otherwise gas-tight devices. Based on
      theoretical predictions for 0.33 mg of sodium bicarbonate and a stoichiometric
      amount of organic acid, the pumping flow rate could be varied from 0.01 microL s(
      1) to 70 microL s(-1). The flow rate is controlled by adjusting any or all of the
      particle size of the least soluble reactant, the amount of reactants used, and
      the type of organic acid selected. The tartaric acid systems rapidly produce
      carbon dioxide; however, the gas generation rates dramatically decrease over the
      course of the reaction. In contrast, carbon dioxide production rate in the
      benzoic acid systems is lower and nearly constant for several minutes. Water
      activation and direct placement on a microfluidic device are key features of this
      micropump, which is therefore useful for portable microfluidic applications.

PMID- 16652183
TI  - Design and fabrication of a multilayered polymer microfluidic chip with
      nanofluidic interconnects via adhesive contact printing.
AB  - The design and fabrication of a multilayered polymer micro-nanofluidic chip is
      described that consists of poly(methylmethacrylate) (PMMA) layers that contain
      microfluidic channels separated in the vertical direction by polycarbonate (PC)
      membranes that incorporate an array of nanometre diameter cylindrical pores. The
      materials are optically transparent to allow inspection of the fluids within the
      channels in the near UV and visible spectrum. The design architecture enables
      nanofluidic interconnections to be placed in the vertical direction between
      microfluidic channels. Such an architecture allows microchannel separations
      within the chip, as well as allowing unique operations that utilize nanocapillary
      interconnects: the separation of analytes based on molecular size, channel
      isolation, enhanced mixing, and sample concentration. Device fabrication is made
      possible by a transfer process of labile membranes and the development of a
      contact printing method for a thermally curable epoxy based adhesive. This
      adhesive is shown to have bond strengths that prevent leakage and delamination
      and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels
      100 microm in width and 20 microm in depth are contact printed without the
      adhesive entering the microchannel. The chip is characterized in terms of
      resistivity measurements along the microfluidic channels, electroosmotic flow
      (EOF) measurements at different pH values and laser-induced-fluorescence (LIF)
      detection of green-fluorescent protein (GFP) plugs injected across the
      nanocapillary membrane and into a microfluidic channel. The results indicate that
      the mixed polymer micro-nanofluidic multilayer chip has electrical
      characteristics needed for use in microanalytical systems.

PMID- 16652184
TI  - Immunosensing of Staphylococcus enterotoxin B (SEB) in milk with PDMS
      microfluidic systems using reinforced supported bilayer membranes (r-SBMs).
AB  - A versatile and novel method has been developed for microfluidic immunosensing of
      the food-borne pathogen Staphylococcus enterotoxin B (SEB) in
      poly(dimethylsiloxane) (PDMS) chips. Supported bilayer membranes (SBMs) were
      generated by vesicle fusion in oxidized PDMS microchannels for minimizing non
      specific adsorption of biomolecules. The stability of SBMs was strengthened with
      a streptavidin layer to make them air-stable and allow for subsequent display of
      the biotin-functionalized antibodies. The reinforced supported bilayer membranes
      (r-SBMs) are fluid, exhibiting a lateral diffusion coefficient of approximately
      1.9 microm(2) s(-1), and no detectable change of mobility was found after
      dehydration/rehydration. This is a substantial improvement over
      phosphatidylcholine (PC) membranes on PDMS, which suffered a roughly 10%
      reduction in the mobile fraction and 30% decrease in mobility after dehydration.
      Non-specific protein adsorption in the membrane-treated channels was reduced 100
      1000 fold as compared to PDMS surfaces without a membrane coating. A flow-based
      microfluidic immunosensor for SEB was developed using antibodies linked to the r
      SBMs in PDMS channels, and a detection limit of 0.5 ng mL(-1) was obtained from
      the linear portion of the calibration curve. The microchip was applied to
      detection of SEB in milk, and similar response and sensitivity were obtained,
      demonstrating the sensor's remarkable performance for real world samples. The r
      SBMs overcome the stability hurdle in SBM-modified surfaces, opening up
      possibilities for transport and storage of membrane-functionalized microchips in
      the dehydrated form without compromising the performance, and facilitating the
      commercialization of disposable SBM-based microdevices.

PMID- 16652185
TI  - A micro-scale multi-frequency reactance measurement technique to detect bacterial
      growth at low bio-particle concentrations.
AB  - The technique described enables the user to detect the presence and proliferation
      of bacteria through an increase in the bulk capacitance (C) of the suspension,
      which is proportional to the bacteria count, at practical frequencies less than 1
      MHz. The geometry of the micro-capillary design employed increases the bulk
      resistance (R) of the medium, thus increasing its RC time. This makes the
      measured reactance sensitive to changes in the bulk capacitance, which is usually
      masked by the much larger surface capacitance. The sensitivity is further
      enhanced by the existence of a minimum in the value of the reactance at a
      frequency proportional to the inverse medium RC time. The value of this reactance
      minimum and the frequency at which the minimum is recorded are dependent on the
      bacteria count and permit the detection of an initial concentration of
      approximately 100 CFU ml(-1) of E. coli within 3 hours of incubation, in
      comparison with the previous reported values of about 8 hours, with an initial
      load of 1000 CFU ml(-1).

PMID- 16652186
TI  - Cardiac troponins--biochemical markers of cardiac toxicity after cytostatic
      therapy.
AB  - Cardiotoxicity is a serious adverse effect of chemotherapy that encompasses a
      spectrum of disorders, ranging from relatively benign arrhythmias to potentially
      lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. The
      toxicity of chemotherapeutic drugs can cause loss of myocytes' sarcolemmal
      integrity, release of bioactive markers into the extracellular environment
      (tissue and circulation) and ultimately leading to the necrosis of myocytes. The
      extent and severity of the necrosis can be monitored by the levels of bioactive
      markers. Therefore current research is aimed at finding biochemical markers with
      absolute cardiac specificity, high sensitivity and predictive value that can be
      used in early detection of patients with treatment-induced myocardial damage.
      Routinely used biomarkers like CK, CK-MB, and myoglobin do not meet the stated
      criteria. Their role in early diagnosis of chemotherapy- induced myocardial
      toxicity is controversial and limited. However, cardiac troponins, new
      nonconventional markers, have shown promising results in assessment and
      monitoring of both, early and late, clinical and subclinical damage to myocardium
      after chemotherapy. The article reviews clinical studies evaluating the role of
      cardiac troponins in the diagnosis of cardiotoxicity and their use in the
      management of cancer survivors.

PMID- 16652187
TI  - Garlic-derived organosulfides induce cytotoxicity, apoptosis, cell cycle arrest
      and oxidative stress in human colon carcinoma cell lines.
AB  - Organosulfur compounds (OSC) from garlic, especially allicin (ALI), diallyl
      sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) are
      recognized as a group of potential chemopreventive agents. In this study, we
      examined the effects of OSC on human Caco-2 and HT-29 colon carcinoma cell lines.
      Apoptosis induction (Annexin-V-FITC/PI, fluorescein diacetate/PI, sub-G1
      fraction), modulation of DNA cell cycle (G2/M arrest, phospho-H3 mitotic marker),
      transmembrane mitochondrial potential (JC-1) and intracellular GSH amount
      (monochlorobimane assay) were measured by flow cytometry and fluorimetry. Our
      results showed that order of OSC-induced cell death in Caco-2 and HT-29 cells
      increased in the range as follows: ALI < DAS = DADS < DATS and ALI = DAS < DADS <
      DATS, respectively. Both cell lines used are relatively resistant to OSC induced
      cytotoxicity, because compound concentrations required to obtain significant
      effect are in high micromolar range. ALI was less toxic than equimolar doses of
      other OSC tested with the exception of GSH modulation and G2/M arrest in Caco-2
      cells. DADS-treated HT-29 cells and both DATS-treated cell lines exhibit inverse
      correlation between p-H3 positivity and compound concentration due to higher
      apoptotic rate. These results show the correlation of sulfur atoms number in OSC
      with their capacity in apoptosis induction and support the role of redox
      sensitive "sulfhydryl switches" in maintaining intracellular redox milieu.

PMID- 16652188
TI  - Effect of IL-18 on leukocyte expression of iNOS and phospho-IkB in patients with
      squamous cell carcinoma of the oral cavity.
AB  - The inducible synthase of nitric oxide (iNOS) is responsible for the synthesis of
      nitric oxide (NO) in neutrophils (PMN) and in peripheral blood mononuclear cells
      (PBMC). This enzyme is controlled by a number of cytokines which accomplish their
      biological effect via e.g. activation of NF-kB pathway. The aim of the present
      study was to assess the expression of iNOS and production of NO by PMN and PBMC
      in patients with oral cavity squamous cell carcinoma (SCC), and to examine the
      role of the NF-kB pathway in the IL-18-stimulated activation of this enzyme. The
      production of NO and iNOS expression in PMN were reduced, while iNOS expression
      in PBMC was increased but NO production by these cells remain unchanged. Patients
      after treatment showed lower intensity of iNOS expression compared to that
      observed before treatment. Moreover, both before and after treatment iNOS
      expression was inversely correlated with phospho-IkB expression in PMN and in
      PBMC. Significantly higher levels of total NO were observed in the serum of Stage
      IV patients before and after treatment as compared to the control group. Altered
      expression of iNOS and NO generation by PMN and PBMC may have an unfavorable
      effect on the course of antineoplastic response in patients with squamous cell
      carcinoma of the oral cavity. Intensification of iNOS expression and NO
      production in Stage IV patients, induced by rhIL-18, suggests its beneficial
      effect on the activity of leukocytes in patients with squamous cell carcinoma of
      the oral cavity.

PMID- 16652189
TI  - Knockdown of survivin gene by vector-based short hairpin RNA technique induces
      apoptosis and growth inhibition in Burkitt's lymphoma Raji cell line.
AB  - Survivin is the smallest member of mammalian IAP (inhibitor of apoptosis) family.
      It is ubiquitous during embryonic development but is not expressed in normal post
      natal tissues, except the thymus, colonic epithelial cells and CD34+
      hematopoietic stem cells. However, its expression is upregulated during
      neoplastic transformation in both solid organ and hematological malignancies,
      including leukemia and lymphoma. In this study, we used RNA interference with
      short hairpin RNA (shRNA) technique to inhibit survivin expression in a Burkitt's
      lymphoma cell line Raji and validated its effects on apoptosis and cell
      proliferation. A survivin-shRNA expression vector were constructed and introduced
      into Raji cells. Expression of survivin mRNA and protein was assessed by RT-PCR
      and western blot analysis. Apoptosis index of transfected cells was quantified by
      flow cytometry and cell proliferation was enumerated by trypan blue exclusion. In
      Raji cells treated with survivin-shRNA expression vector, survivin mRNA levels
      were significantly reduced by 67.14% (transient transfection) and 64.28% (stable
      transfection) respectively, compared with control-shRNA treated group and PBS
      treated group (p<0.05). The levels of survivin protein were significantly reduced
      by 62.50% (transient transfection) and 60.93% (stable transfection), compared
      with the two control groups (p<0.05). Apoptosis index was significantly increased
      during transient transfection and stable transfection, respectively 31.20+/-2.45%
      and 29.40+/-1.72% (p<0.05). Survivin-shRNA inhibited the proliferation of Raji
      cells of stable transfection. In conclusion, the vector-based survivin-shRNA can
      effectively reduce the expression of survivin gene and induce apoptosis and
      growth inhibition of transfected Raji cells. We suggest that survivin can be
      regarded as an ideal target for new anticancer intervention of NHL.

PMID- 16652190
TI  - Prognostic significance of plasma cell propidium iodide and annexin-V indices and
      their mutual ratio in multiple myeloma.
AB  - The aim of this study was a contemporaneous measurement of plasma cells
      proliferative and apoptotic activity in patients examined at the time of multiple
      myeloma (MM) diagnosis before initiation of chemotherapy, focussed on the
      following aspects: determination of prognostic significance of plasma cell
      propidium iodide (PC-PI) and annexin-V FITC (PC-AI) indices; optimal cut off of
      PC-PI and PC-AI with regard to overall survival; calculation of summary kinetic
      index of plasma cells (PC-PI/AI ratio) for evaluation of its prognostic
      importance; determination of an index (out of PC-PI, PC-AI and PC-PI/AI) showing
      the closest relation to prognosis of multiple myeloma. The analyzed 122 patients
      fulfilling SWOG multiple myeloma criteria were treated by conventional
      chemotherapy. Plasma cell proliferative activity was measured by means of PC-PI
      examined by flow cytometry using a DNA/CD138 double staining technique. For
      detection of plasma cells entering apoptosis (PC-AI), flow-cytometry method with
      annexin-V FITC and MoAb CD138 was used. The PC-PI median in 122 patients was
      2.6(0.4-4.8)%. The sequence prognostic analysis showed that the optimal PC-PI cut
      off was 2.9% and displayed a significant relationship with overall survival (OS)
      (p=0.031). The group of 94 patients had PC-AI median of 5.0(1.4-24.5)%. The best
      statistical significance of the rate of apoptosis related to overall survival was
      found at cut off value of 4.4% (p=0.022). The median of overall kinetic index of
      plasma cells (PC-PI/AI) examined in 94 MM patients was 0.5(0.05-2.60) and the
      overall kinetic index was found to display a very good relationship to OS at the
      cut off value of 0.71 (p=0.032). All the three indices expressing various aspects
      of kinetics of plasma cells allow the stratification of patients into two
      prognostically different groups with statistically significantly different
      medians of overall survival: good risk - OS still undeterminable at the time of
      analysis; bad risk - M: OS was for PC-PI 17 months, for PC-AI 23 months and for
      PC-PI/AI 16 months. The ratio of both indices, i.e. PC- PI/AI, however did not
      bring any further contribution to overall survival/prognosis evaluation, when
      compared with single PC-PI and PC-AI. Results of present study indicates that the
      evaluation of both proliferation and apoptotic activities of plasma cells is
      important for prognosis thus extending possibilities of initial stratification of
      MMpatients into groups with different prognostic risk.

PMID- 16652191
TI  - Prognostic relevance of the FAB morphological criteria in chronic lymphocytic
      leukemia: correlations with IgVH gene mutational status and other prognostic
      markers.
AB  - Morphological examination is the routine first step in the diagnosis of
      hematological malignancies, including chronic lymphocytic leukemia (CLL).
      Atypical cell morphology according to the FAB criteria is known to herald disease
      progression. Several years ago, it was proposed that FAB morphology at diagnosis
      had a considerable prognostic impact. However, this proposal has not been widely
      adopted in practice. Thus we questioned the prognostic value of the morphological
      examination, which was performed retrospectively in 88 patients out of our 110
      institutional registry patients (70 males and 40 females, median age 57 yrs) with
      CLL at diagnosis. We related the results to the more modern prognostic markers.
      Atypical FAB morphology was shown to correlate with IgVH gene mutation status,
      trisomy of chromosome 12 and deletion of 17p detected either by conventional G
      banding or by fluorescence in situ hybridization (FISH) analysis. The correlation
      of FAB morphology with CD38 antigen expression or with the histopathological
      pattern of bone marrow infiltration was not significant. Overall survival (OS)
      data were available for 84 morphologically examined patients. The patients with
      atypical morphology (64 patients) had a significantly shorter OS (103 months)
      than the 20 patients presenting with typical CLL morphology (237 months; p=0.03).
      Only the mutation status of IgVH genes correlated more closely with OS (p=0.002).
      Of note, there was no leukemia-related death within "unmutated" cases who had
      typical FAB morphology (p=0.14), and vice versa, the mutation status had a
      significant prognostic impact within the morphologically atypical cases (p=0.01).
      Thus FAB morphology and the mutation status may yield complementary prognostic
      information. OS was affected both by the presence of cytogenetic aberrations
      (p=0.03) - most adversely by deletions of 17p and 11q, and by CD38 expression
      (p=0.003). We conclude that careful examination of peripheral blood smears
      according to FAB is a simple, cheap and valuable tool in the first-line
      assessment of prognosis of CLL patients and should not be overlooked even in 3rd
      millennium when more sophisticated prognostic markers are at hand. This ought to
      be confirmed in larger prospective studies with multivariate analysis of data.

PMID- 16652192
TI  - Induction of drug resistance in embryonal rhabdomyosarcoma treated with
      conventional chemotherapy is associated with HLA class I increase.
AB  - Effectiveness of conventional cytotoxic treatment of rhabdomyosarcoma (RMS) may
      be limited by the development of multidrug resistance (MDR) mediated by mdr1
      gene. This gene codes for P-glycoprotein (P-gp) which has been related to a
      immunoregulatory function. Modulation of HLA expression by P-gp has been
      described in different types of tumor cells including RMS. However, very little
      is known about biological implications of the P-gp expression in RMS patients
      treated with conventional chemotherapy. In order to study the problem, we used
      embryonal RMS tissue samples from treated patients. Our results indicated that
      positive RMS samples to mdr1 show higher HLA class I expression than those which
      were negative to mdr1 PCR, what indicates a significant correlation between the
      expression of both molecules. In addition, we developed two resistant RMS cell
      lines (A-204-1 and 2) using similar concentrations of actinomycin D as are plasma
      levels in clinical situation. Both resistant cell lines showed mdr1 expression
      and an increase of HLA class I expression which was dose-dependent. These results
      demonstrated that conventional chemotherapy of embryonal RMS is able to induce
      resistance which can modulate HLA class I expression and suggest that
      immunological studies of these tumors may be necessary to the design new specific
      therapeutic strategies.

PMID- 16652193
TI  - High dose rate brachytherapy in the treatment of oral cancer--the preliminary one
      institution experience.
AB  - Low dose rate brachytherapy is well established treatment modality of oral
      cancer. Data about high dose rate brachytherapy (HDR BT) are still scarce with
      heterogenous results. The aim of our study was to evaluate preliminary results in
      a small group of oral cancer patients treated by HDR BT. Seventeen applications
      were performed on 16 patients in years 2001-2004, in 15 cases for new tumor
      (mobile tongue 10x, floor of mouth 2x, lip 3x) and in 2 cases for local
      recurrence after radiotherapy. Ten treatments (for T1-2N0 tumors and recurrences)
      were performed with brachytherapy alone (18 x 3 Gy twice daily), seven patients
      (T2-3 N0-2 tumors) were treated with a combination of external beam radiotherapy
      (40-68 Gy) and brachytherapy (2-6 x 3 Gy twice daily). The plastic tubes
      technique was used for brachytherapy. Follow-up periods were between 8-46 months
      (median 17). Fifteen patients were disease free during follow-up period. One
      patient (brachytherapy alone for T2N0M0 mobile tongue cancer) died immediately
      after neck dissection for the neck recurrence due to the heart failure. The other
      one died due to distant metastases but without local recurrence. Acute
      complications were mucositis gr. II at maximum, late complications were ulcer of
      soft tissues in 3 and superficial bone necrosis in 2 cases. The evaluation of the
      brachytherapy implants was done according ICRU 58 recommendations.
      Hyperfractionated high dose rate brachytherapy alone or as a boost to external
      beam radiotherapy is feasible with promising local control. Carefull planning of
      the implant and mandibular shielding are necessary to avoid complications.

PMID- 16652194
TI  - Performance of opportunistic breast cancer screening in Slovenia.
AB  - The purpose of the study was to assess performance indicators of opportunistic
      breast screening carried out in one of the Primary Breast Diseases Centers (PBDC)
      and to find out if these indicators meet the standards set in "European
      guidelines for quality assurance in mammographic screening". The records of 1,896
      asymptomatic women, aged between 50 and 69 years who attended PBDC for the first
      time in the period from October 15 1998 to October 15 2002, were reviewed. In all
      of them, clinical examination and mammography was done. If necessary, non
      invasive additional imaging was also performed in the PBDC. If malignancy could
      not be excluded, the women were referred to the Institute of Oncology (IO) for
      additional invasive diagnostic procedures. The data on these findings were
      collected from the records of the IO. We compared our results with the
      recommended values of performance indicators valid for organized screening
      programs as determined by "European guidelines". Of 1,896 women, 415 (22%) were
      recalled for additional imaging. In 335/415 women the suspicion for malignancy
      was excluded with noninvasive diagnostic methods. Invasive diagnostic procedures
      were applied in 80/415 women. Carcinomas were detected in 23 women, the majority
      of them (96%) were non palpable. All carcinomas were ductal; 9 (39%), 7 (30.5%),
      7 (30.5%) were grade 1, 2 and 3, respectively. One carcinoma was preinvasive; 20
      had the tumor size T1, 1 had T2, while in one the size was not specified. The
      axillary lymph nodes were negative in 14/23 (61%) women with invasive carcinoma
      and positive in 5/23 (22%). Surgery of the axilla was considered unnecessary in
      4/23 (17%). Diagnostic sensitivity in presented cohort was 96%, specificity 79%.
      After a negative mammogram 1 interval cancer was detected. Compared to the
      "European guidelines" we achieved satisfactory results in the number and size of
      detected and interval cancers, but the analysis showed a higher recall rate with
      too many false-positive results. Efforts should target lowering the recall rate
      without reducing the cancer detection rate. Compared to Slovenian average, a
      large percentage of localized breast cancers in our study claim for organized
      breast cancer screening program in Slovenia at earliest convenience.

PMID- 16652195
TI  - Evaluation of tumor angiogenesis and thymidine phosphorylase tissue expression in
      patients with endometrial cancer.
AB  - The formation of new blood vessels in endometrial cancer tissue is a main
      process, which leads to tumor progression, and is connected with tumor expansion
      and invasiveness. The aim of the study was evaluation of thymidine phosphorylase
      protein (TP) expression in human endometrial cancer cells by immunohistochemistry
      and comparison obtained data with intensity of angiogenesis process and
      clinicopathological factors as FIGO stage of disease and histopathologic grade.
      Endometrial cancer specimens were obtained from 55 postmenopausal patients (aged
      52 to 74 years) underwent total abdominal hysterectomy with bilateral salpingo
      oophorectomy. None of patients received preoperative pelvic irradiation.
      Histopathological typing and grading of the endometrial tumors (G-1, G-2, G-3) as
      well as myometrial invasion (<1/2, >1/2) were assessed using standard criteria,
      on hematoxylin-eosin sections. At the surgery, FIGO clinical stage of disease was
      determined. Thymidine phosphorylase overexpression was observed in 23 of 55
      (41.8%) cases of endometrial cancer. Although we found no statistically
      significant differences in TP expression between histopathologic grades,
      particular FIGO stages showed a significant trend of increase TP tumor
      overexpression. Thymidine phosphorylase overexpression cases demonstrate higher
      intensity of angiogenesis in comparison to negative samples and results are
      statistically significant for t-test (p<0.0001). The most intensive new blood
      vessel formation was observed in G-2 of tumor differentiation grade (p=0.013 for
      ANOVA test) Mean angiogenic points density (APD) values in cases of G-1
      histopathologic grade reached 135.7; values of G-2 and G-3 grades reached 213.8
      and 162.8, respectively. Mean intensity of angiogenesis in the first FIGO stage
      of disease reached 160.0 APD, in stage II 205.6 APD, and in the third 286.9,
      respectively. Angiogenesis was more intensive in cases of advanced tumors -
      analysis of variance (ANOVA) confirmed statistically significant differences in
      APD values between FIGO stage groups (p=0.0007). In conclusion, thymidine
      phosphorylase expression correlates with increased microvessel density in
      endometrial cancer. The intensity of angiogenesis process increases according to
      FIGO stage of disease, which is connected with progressing of cancer disease.
      Thymidine phosphorylase can play an important role in endometrial cancer
      progression and could offer additional information about advance of disease.

PMID- 16652196
TI  - A correlation of microvascular density and proliferative activity to clinical and
      histological characteristics in neuroblastoma.
AB  - Seventy-four neuroblastoma patients were analyzed according to the clinical data
      including age, stage, bone metastases, primary tumor localization, tumor
      diameter, LDH, and serum ferritin. Histological examination of tumor specimens
      comprised calculation of proliferative index (PI) on slides stained with anti Ki
      67 antibody and assessment of microvascular density (MVD) on anti-CD34 stained
      sections. Wide range of PI (1.5-79; median 37.8%) and MVD (41-385; median
      172/mm2) values was observed. Significant relationship between higher PI and
      tumor diameter more than 5 cm (40.3 vs 37.2%) was found. Lower PI was found more
      frequently in stroma-rich tumors. Significantly higher median MVD was found in
      infant tumors and in smaller tumors <5 cm. Tendency to inverse relationship
      between PI and MVD was observed. The high values of both PI and MVD were found in
      some aggressive tumors in patients >1-year old. We evaluated the new parameter:
      proliferative-vascular index (PVI) as PVI=PIxMVD which ranged from 213-18333.
      Among eleven patients >1 year old, with PVI >7000, seven (64%) had a poor outcome
      within the mean period of 22 months. Our results suggest that the simultaneous
      estimation of proliferative activity and vascularity of neuroblastomas could be
      studied as a prognostic indicator. Further investigations are needed to confirm
      this finding.

PMID- 16652197
TI  - Angiogenic and coagulation-fibrinolysis factors in non Hodgkin's lymphoma.
AB  - High serum VEGF and bFGF levels are independent prognostic factors of poor
      prognosis in NHL patients. There is growing evidence that both angiogenesis and
      haemostatic aberrancies are integral parts of the pathobiology of cancer growth
      and dissemination. The purpose of the study was: (a) to analyze relations of VEGF
      and bFGF serum levels, fibrinogen and D-dimer plasma levels with lymphoma Ann
      Arbor Staging System (AASS) and International Prognostic Index (IPI) and, (b) to
      evaluate correlations between serum levels of angiogenic cytokines and plasma
      levels of coagulation-fibrinolysis factors in 52 previously untreated NHL
      patients included to the study. The control group consisted of 23 healthy
      volunteers. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme
      linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined
      on Behring Coagulation System (BCS) equipment. In lymphoma group serum VEGF and
      bFGF levels were significantly higher than in the control. Differences in
      concentrations of VEGF, bFGF between II, III and IV stage of disease acc. AASS
      were not statistically significant. Plasma levels of fibrinogen and D-dimer were
      elevated in lymphoma patients when compared with the control. Fibrinogen plasma
      levels were similar in all stages. The D-dimer level was significantly higher in
      patients with IV stage in comparison to stage II and III. Statistically
      significant differences of VEGF and bFGF serum levels were observed only between
      intermediate/high and high risk groups acc. IPI. Fibrinogen plasma levels were
      significantly higher in high risk group than in low risk group. D-dimer plasma
      levels were significantly higher in high risk group than in low risk group and
      low/intermediate group. We observed positive correlation between serum level of
      VEGF and plasma level of fibrinogen, and between serum level of bFGF and plasma
      level of fibrinogen. There was also negative correlation between serum level of
      VEGF and plasma level of D-dimer, and between serum level of bFGF and plasma
      level of D- dimer. Our study indicates that D-dimer level, but not VEGF, bFGF and
      fibrinogen correlates with AASS and IPI in NHL patients. Significant correlations
      between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions
      between angiogenic and coagulation-fibrinolysis system.

PMID- 16652198
TI  - Expression and prognostic significance of Cathepsin L in early cutaneous
      malignant melanoma.
AB  - Cathepsins are papain-like lysosome cysteine proteases involved in tumor growth,
      invasiveness and spread, angiogenesis and alteration in immune and inflammatory
      responses. We investigated the differences in cathepsin L (CatL) concentrations
      in primary cutaneous malignant melanoma stage I and normal skin and correlated
      these values with well-established malignant melanoma prognostic factors. The
      study was performed on 36 patients (17 men and 19 women; mean age 54 years; range
      21-84 years) with histological confirmed primary malignant melanomas less than
      1.5 mm thick. The CatL concentrations were measured in 36 pairs of triton
      extracts of cytosols prepared from the tumor and adjacent normal tissue samples
      (matched pairs). The CatL concentrations were determined by commercially
      available enzyme-liked immunosorbent (ELISA) assay from KRKA (Novo Mesto,
      Slovenia). Significantly higher concentrations of CatL were detected in malignant
      melanomas than in normal surrounding skin (6.73 vs. 1.42 ng/mg total protein
      (mgp), p<0.001). Significant correlations between malignant melanoma and normal
      skin concentrations for CatL were found. The malignant melanoma CatL
      concentrations correlated significantly with normal skin (r=0.38; p=0.021). CatL
      concentrations were significantly lower (p<0.01) in the malignant melanomas of
      Breslow thickness <or=0.75 mm, Clark invasion <II, without microscopic ulceration
      and without vascular invasion (4.14, 4.73, 6.15, 5.29 ng/mgp, respectively) than
      in the malignant melanomas of Breslow thickness >0.75 mm, Clark invasion of
      >or=II and <or=III, with microscopic ulceration and with vascular invasion (7.67,
      7.41, 9.15, 10.35 ng/mgp, respectively). Higher CatL concentrations in early
      primary malignant melanomas indicate its possible involvement in the processes of
      early metastatic spread and its association with poor prognosis.

PMID- 16652199
TI  - Preoperative radiotherapy for locally advanced rectal cancer and prognostic
      factors influencing outcome.
AB  - The aim of presented study was to evaluate the impact of different factors on
      survival, local recurrence and development of metastatic disease in patients with
      rectal cancer treated with preoperative radiotherapy or 5-fluorouracil (5-FU)
      based concurrent chemoradiation. Retrospective clinical evaluation was performed
      in 165 patients (33% women and 67% men) with locally advanced rectal
      adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the
      period January 1998 - March 2003. Tumor extent was evaluated by CT and/or MRI
      and/or TRUS examination and tumor biopsy was performed during colonoscopy. The
      median follow up is 21 month. All patients received preoperative external beam
      radiation to primary tumor, adjacent lymphnodes and presacral region. Computed
      tomography localisation of target volume was used for 3D radiotherapy treatment
      planning. Accelerated short term regimen (25 Gy/5 fraction/1 week) was performed
      in 14% of patients especially in year 1998-2000 and normofractionated regimen (40
      50 Gy/20-25 fractions/4-5 weeks) was performed in 86% of patients.
      Chemoradiotherapy with 5-FU was carried out in 22% of patients. Radical resection
      underwent 85% of patients, inoperable tumor persisted in 7% and distant
      metastases were detected peroperatively in 8%. The 2-year overall survival (OS)
      was 84% and 5-year OS was 60% following radical resection. The important
      prognostic factors affecting survival were postradiotherapy determined
      pathological staging (p=0.005), postradiotherapy tumor grade (p<0.001) and the
      presence of angioinvasion and/or perineural spread (p=0.023). Prognostic factors
      for disease-free survival were identical with those for OS. Higher local
      recurrence rate was associated in preradiotherapy tumor staged T4 (p=0.048) and
      in presence of angioinvasion and/or perineural spread (0.049). Age, tumor
      location, histological grade before radiotherapy and tumor downstaging were not
      statistically significant for survival and/or for local recurrence rate. The best
      survival rates were obtained in patients with postradiotherapy grade 1 tumors (5
      years survival 100%), tumors without angioinvasion and perineural spread (5-years
      survival 65%) and in patients who obtained complete remission after preoperative
      radiotherapy (5-years survival 86%).

PMID- 16652202
TI  - The perichondrial ring as a reservoir for precartilaginous cells. In vivo model
      in young chicks' epiphysis.
AB  - BACKGROUND: The purpose of this study is to illustrate the routes of migration of
      precartilaginous cells from the perichondrial ring of LaCroix, as a potential
      reservoir for growth-plate germ cells. METHODS: Chondrocytes derived from the
      ring of LaCroix of young chicks' proximal tibia were cultured in vitro and
      transfected with adenovirus vector containing the gene encoding for Escherichia
      coli (beta)-galactosidase (lacZ) gene, which allows assessment of the migratory
      routes of these cells. The lacZ- transfected cells were injected back into the
      perichondrial ring of LaCroix of young chicks' proximal tibias. Four weeks later
      the migration root was assessed microscopically. RESULTS: Injection of cells
      derived from the ring of LaCroix of neonate chicks, transfected in culture with
      adenoviruses containing LacZ reporter gene, allows the assessment of migratory
      potential of these cells. Stained cells were found at the outer layer of the
      epiphysis, particularly in areas adjacent to the perichondrial ring. Further
      longitudinal histopathological studies along the bone axis demonstrated a
      condensed layer of the stained cells arranged horizontally along parts of the
      physis. CONCLUSION: The perichondrial ring of LaCroix represents a potential
      reservoir of growth-plate germ cells in young chicks.

PMID- 16652201
TI  - A comparison of stimulus synchronous activity in the primary motor cortices of
      athletes and non-athletes.
AB  - In this study, we measured primary motor cortex (MI) activity during a reaction
      time task to examine the appearance of MI activity that synchronized with the
      stimulus presentation (stimulus synchronous MI activity, SSMA). Because brain
      activity was expected to be enhanced by the repetitive/extensive activation, we
      hypothesized that the SSMA would be more clearly observable in athletes who were
      trained to perform reactive movements than in non-athletes. MI activity was
      measured in ten athletes and ten non-athletes by magnetoencephalography. The
      tasks were a simple reaction task and a Go/Nogo reaction task in which the
      subjects were asked to abduct their right index fingers in response to a visual
      stimulus. The Go/Nogo reaction time task was adopted to confirm the presence of
      the SSMA, because the MI activity in response to a Nogo stimulus did not overlap
      with the MI activity that was synchronous with the execution of the movement. The
      results show that the SSMA was clearly apparent in the athlete group (9/10). In
      the non-athlete group, however, only three subjects showed the SSMA (3/10).
      Moreover, the MI activity of the athletes tended to be larger than that of the
      non-athletes, even though the athletes did not specifically practice these index
      finger movements during their daily training. We concluded that long-term
      physical training promotes MI activity and the effects of reactive task
      repetition were more clearly apparent in the MI activity of the athletes.

PMID- 16652203
TI  - Straining-cremasteric reflex: identification of a new reflex and its role during
      increased intra-abdominal pressure.
AB  - The cremasteric muscle (CM) being composed of fleshy muscle bundles constitutes
      the active component of the fasciomuscular tube of the spermatic cord. On
      contraction, the CM compresses the cord veins pushing the blood in the
      pampiniform plexus to the abdominal veins. The role of the CM during increased
      intra-abdominal pressure (IAP) could not be traced in the literature. We
      investigated the hypothesis that the CM contracts upon IAP increase so as to
      support the cord veins and prevent abdominal veins reflux into them. Thirty-two
      healthy male volunteers (mean age 40.2 +/- 11.2 SD years) were studied. The IAP
      was recorded by a manometric catheter introduced into the rectum. The CM response
      to straining (sudden by coughing and slow by Valsalva's maneuver) was registered
      by a needle electrode introduced into the muscle. The response was recorded again
      after individual anesthetization of the CM and rectum. The test was repeated
      using saline instead of lidocaine and was performed on both sides. Straining
      (sudden or slow sustained) effected increase of the rectal pressure and CM EMG.
      The more the rectal pressure was increased by straining, the more the CM EMG was
      increased. The CM EMG response disappeared after prolonged or repeated successive
      straining. The CM did not respond to straining after individual anesthetization
      of the rectum and CM but did respond to saline administration. The response was
      similar from muscles on both sides. Increased CM EMG on straining postulates a
      reflex relationship which we call the 'straining-cremasteric reflex' (SCR). We
      suggest that this reflex, which results in CM contraction, supports the spermatic
      cord veins against the increase of the IAP induced by straining and against the
      tendency of venous reflux from the abdominal veins. The SCR may prove of
      diagnostic significance in neurogenic disorders provided further studies are
      performed in this respect.

PMID- 16652204
TI  - The production of a new extracellular putative long-chain saturated polyester by
      smooth variants of Mycobacterium vaccae interferes with Th1-cytokine production.
AB  - Mycobacterium vaccae is of major pharmaceutical interest as an immunotherapeutic
      agent. Although M. vaccae 15483 ATCC(T) strain displays smooth and rough colonial
      morphologies on solid culture media, it is not known in which conditions M.
      vaccae switches from one colonial morphotype to the other or whether there are
      biological differences, especially immunological, between them. We have found
      that the change from a smooth to rough stable variant occurs spontaneously at 30
      degrees C. The analysis of the composition of the cell wall in both variants
      showed that the smooth morphotype presents an extracellular material that has
      never previously been described and was identified as a long-chain saturated
      polyester that, interestingly, is not produced by the rough morphotype. Our
      results also indicate that this compound could be implicated in the spreading
      ability of smooth colonies. Proliferation, IFN-gamma and IL-12(p40) production by
      splenocyte cultures was significantly higher in mice immunised with the rough
      variant compared with those immunised with the smooth one. This latter finding
      suggests that the different colonial morphology of M. vaccae may affect the
      immunomodulatory effects induced from M. vaccae preparations.

PMID- 16652205
TI  - Polysaccharides and phenolic compounds as substrate for yeasts isolated from
      rotten wood and description of Cryptococcus fagi sp.nov.
AB  - Pieces of rotten wood collected in the forest were screened for the presence of
      yeasts. In spring time 3 tree species were sampled, followed by 9 species in
      summer. Yeast strains were identified by traditional methods. Identifications
      were confirmed by sequencing of ribosomal DNA in case of doubt. In total 14 yeast
      species of ascomycetous affiliation and 6 anamorphic basidiomycetous yeasts were
      isolated and identified. Most species were represented by only one strain, but
      Candida bertae by two and Trichosporon porosum by six strains, all from different
      wood samples. Three strains represented novel species, one of which is described
      as Cryptococcus fagi Middelhoven et Scorzetti. The type strain is CBS 9964 (JCM
      13614). All strains were tested for growth on several polysaccharides as sole
      carbon source. Only some of these polymers supported growth of ascomycetous
      yeasts. Basidiomycetous yeasts assimilated soluble starch, pullulan, dextran,
      xylan, polygalacturonate, galactomannan and tannic acid or at least some of
      these. Cryptococcus podzolicus and T. porosum were the most active in this
      respect. None of the isolated strains grew on carboxymethyl cellulose, colloidal
      chitin, arabinogalactan and gum xanthan. Phenolic compounds were assimilated by
      several strains, belonging to the Trichosporonales and the Microbotryum and
      Stephanoascus/Blastobotrys clades, but not by members of the Tremellales
      (Cryptococcus musci excepted) and the Debaryomyces/Lodderomyces clade. Most of
      the ascomycetes assimilated n-hexadecane.

PMID- 16652206
TI  - Dominance of Lysobacter sp. in the rhizosphere of two coastal sand dune plant
      species, Calystegia soldanella and Elymus mollis.
AB  - Bacterial diversity in the rhizosphere of beach morning glory (Calystegia
      soldanella) and wild rye (Elymus mollis), two of the major plant species
      inhabiting the coastal sane dune in Tae-An, Korea, was studied by the analysis of
      community 16S rRNA gene clones. The amplified rDNA restriction analysis (ARDRA)
      of the clones using HaeIII exhibited significant differences in the community
      composition between the two plant species as well as regional differences, but
      also identified a specific ARDRA pattern that was most common among the clones
      regardless of plant species. Subsequent sequence analysis indicated that the
      pattern was that of Lysobacter spp., which is a member of the family
      Xanthomonadaceae, class Gamma proteobacteria. The Lysobacter clones comprised
      50.6% of the clones derived from C. soldanella and 62.5% of those from E. mollis.
      Other minor patterns included those of Pseudomonas spp., species of Rhizobium,
      Chryseobacterium spp. and Pantoea spp. among C. soldanella clones, and
      Pseudomonas sp. and Aeromonas hydrophila among E. mollis clones. It is not yet
      clear what kind of roles Lysobacter plays in association with sand dune plants,
      but its universal presence in the rhizosphere, together with the potential of
      this taxon for antagonistic activity against plant pathogens, suggests that
      Lysobacter might form a symbiotic relationship with its host plants.

PMID- 16652207
TI  - Protein Alpha Shape (PAS) Dock: a new gaussian-based score function suitable for
      docking in homology modelled protein structures.
AB  - Protein Alpha Shape (PAS) Dock is a new empirical score function suitable for
      virtual library screening using homology modelled protein structures. Here, the
      score function is used in combination with the geometry search method Tabu
      search. A description of the protein binding site is generated using gaussian
      property fields like in Protein Alpha Shape Similarity Analysis (PASSA). Gaussian
      property fields are also used to describe the ligand properties. The overlap
      between the receptor and ligand hydrophilicity and lipophilicity fields is
      maximised, while minimising steric clashes. Gaussian functions introduce a
      smoothing of the property fields. This makes the score function robust against
      small structural variations, and therefore suitable for use with homology models.
      This also makes it less critical to include protein flexibility in the docking
      calculations. We use a fast and simplified version of the score function in the
      geometry search, while a more detailed version is used for the final prediction
      of the binding free energies. This use of a two-level scoring makes PAS-Dock
      computationally efficient, and well suited for virtual screening. The PAS-Dock
      score function is trained on 218 X-ray structures of protein- ligand complexes
      with experimental binding affinities. The performance of PAS-Dock is compared to
      two other docking methods, AutoDock and MOE-Dock, with respect to both accuracy
      and computational efficiency. According to this study, PAS-Dock is more
      computationally efficient than both AutoDock and MOE-Dock, and gives a better
      prediction of the free energies of binding. PAS-Dock is also more robust against
      structural variations than AutoDock.

PMID- 16652208
TI  - Involvement of ERK1/2 and p38 in Mg2+ accumulation in liver cells.
AB  - Activation of PKC signaling induces Mg(2+) accumulation in liver cells. To test
      the hypothesis that PKC induces Mg(2+) accumulation via MAPKs activation,
      hepatocytes were incubated in the presence of PD98059 and SB202190 as specific
      inhibitors of ERK1/2 and p38, respectively, and stimulated for Mg(2+)
      accumulation by addition of PMA or OAG. Accumulation of Mg(2+) within the cells
      was measured by atomic absorbance spectrophotometry in the acid extract of cell
      pellet. The presence of either inhibitor completely abolished Mg(2+) accumulation
      irrespective of the dose of agonist utilized while having no discernible effect
      on beta -adrenoceptor mediated Mg(2+) extrusion. A partial inhibition on alpha
      (1)-adrenoceptor mediated Mg(2+) extrusion was observed only in cells treated
      with PD98059. To confirm the inhibitory effect of PD98509 and SB202190, total and
      basolateral liver plasma membrane vesicles were purified in the presence of
      either MAPK inhibitor during the isolation procedure. Consistent with the data
      obtained in intact cells, liver plasma membrane vesicles purified in the presence
      of PD98509 or SB202190 lost the ability to accumulate Mg(2+)in exchange for intra
      vesicular entrapped Na(+) while retaining the ability to extrude entrapped Mg(2+)
      in exchange for extra-vesicular Na(+). These data indicate that ERK1/2 and p38
      are involved in mediating Mg(2+) accumulation in liver cells following activation
      of PKC signaling. The absence of a detectable effect of either inhibitor on beta 
      adrenoceptor induced, Na(+)-dependent Mg(2+) extrusion in intact cells and in
      purified plasma membrane vesicles further support the hypothesis that Mg(2+)
      extrusion and accumulation occur through distinct and differently regulated
      transport mechanisms.

PMID- 16652209
TI  - Cytotoxic and antiproliferative effects induced by a non terpenoid polar extract
      of A. indica seeds on 3T6 murine fibroblasts in culture.
AB  - Neem oil is a natural product obtained from the seeds of the tree Azadirachta
      indica. Its composition is very complex and the oil exhibits a number of
      biological activities. The most studied component is the terpenoid azadirachtin
      which is used for its insecticidal and putative antimicrobial properties. In this
      report we investigate the biological activity of partially purified components of
      the oil obtained from A. indica. We show that the semi-purified fractions have
      moderate to strong cytotoxicity. However, this is not attributable to
      azadirachtin but to other active compounds present in the mixture. Each fraction
      was further purified by appropriate extraction procedures and we observed a
      differential cytotoxicity in the various sub-fractions. This led us to
      investigate the mode of cell death. After treatment with the oil fractions we
      observed positivity to TUNEL staining and extensive internucleosomal DNA
      degradation both indicating apoptotic death. The anti-proliferative properties of
      the neem oil-derived compounds were also assayed by evaluation of the nuclear
      PCNA levels (Proliferating Cell Nuclear Antigen). PCNA is significantly reduced
      in cells treated with a specific fraction of neem oil. Finally, our results
      strongly suggest a possible involvement of the mitochondrial pathway in the
      apoptotic death.

PMID- 16652215
TI  - Superior mesenteric artery pseudoaneurysm associated with celiac axis occlusion
      treated using endovascular techniques.
AB  - The case of a 30-year-old woman with a post-traumatic pseudoaneurysm of the
      superior mesenteric artery and associated celiac axis occlusion is presented. The
      patient was successfully treated with celiac artery recanalization and placement
      of a covered stent within the superior mesenteric artery. Follow-up at 3, 6, and
      12 months and 3 years demonstrated patency of the covered stent and continued
      exclusion of the aneurysm. Although the long-term success of this procedure is
      unknown this management option should be considered where facilities are
      available, to reduce the increased morbidity associated with open surgical
      procedure.

PMID- 16652216
TI  - Haemophilus influenzae type b and pertussis vaccinations in preterm infants.
AB  - INTRODUCTION: The aim of the study was to evaluate the serological efficacy of
      Hiberix and Infanrix-DTPa vaccines in preterm infants. MATERIALS AND METHODS: The
      results of the investigation of 61 preterm infants immunized three times (primary
      vaccination) with Hiberix and Infanrix-DTPa at 6-week intervals are presented. Of
      the 61 children, 17 were additionally immunized with a booster dose of these
      vaccines. Postvaccinal response to these immunizations was evaluated by means of
      an immunoenzymatic method. RESULTS: We observed a significant increase in
      protective postvaccinal antibody titers against Haemophilus influenzae type b
      (Hib) and Bordetella pertussis after the primary vaccination compared with the
      initial antibody levels (p<0.05). A significant increase (p<0.0002) in protective
      antibody titers after the booster dose of Hiberix compared with the primary
      vaccination was also noted. No correlations between birth weight, gestational
      age, and the achieved levels of postvaccinal anti-polyribosylribitol phosphate of
      Hib and of anti-pertussis toxin and anti-filamentous hemagglutinin of B.
      pertussis antibodies after the primary vaccination or booster dose were found.
      After the booster dose, all the preterm infants responded with the production of
      protective postvaccinal antibody titers against Hib and B. pertussis.
      CONCLUSIONS: Due to the very good immunogenicity of the vaccines against Hib
      studied, inclusion of this immunization should be proposed in the obligatory
      vaccination schedule in Poland, especially in preterm infants. An additional
      immunization (i.e. a second booster dose) of Polish children with acellular
      pertussis (DTPa) vaccine is necessary to protect them from decreasing protective
      anti-pertussis antibody titers in early childhood.

PMID- 16652217
TI  - Modulation of apoptosis signaling for cancer therapy.
AB  - Apoptosis, the cell's intrinsic death program, plays a central role in regulating
      tissue homeostasis. Also, most cytotoxic therapies used for cancer treatment,
      such as chemotherapy, gamma-irradiation, suicide genes, or immunotherapy,
      predominantly act by triggering apoptosis in target cells. Thus, understanding
      the molecular events that regulate apoptosis and how tumor cells evade apoptotic
      deletion have provided a paradigm to link cancer genetics and response to cancer
      therapy. Therefore, insights into the mechanisms regulating drug-induced
      apoptosis provide rational targets for novel therapeutic interventions.

PMID- 16652218
TI  - Impact of fetal-maternal tolerance in hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is known to cure
      various hematological disorders; however, its widespread use is limited due to a
      lack of histocompatible donors. Reciprocal cell traffic between the mother and
      fetus during pregnancy gives rise to postpartum fetal-maternal
      lymphohematopoietic microchimerism, which is frequently detected in the blood or
      tissue of healthy individuals. Studies in clinical and experimental
      transplantation provide evidence that exposure to non-inherited maternal antigens
      (NIMAs) during pregnancy may result in long-lasting fetomaternal microchimerism
      and tolerance induction. Studies of HLA-mismatched HSCT have suggested a
      relatively lower incidence of severe graft-versus-host disease (GVHD) after
      transplantation from a NIMA-mismatched donor. Studies using a mouse model have
      also demonstrated a "child-to-mother" bone marrow transplantation from an NIMA
      exposed donor to reduce the morbidity and mortality of GVHD in an antigen
      specific manner while preserving the graft-versus-leukemia effects and favoring
      the immune reconstitution, thus resulting in a marked improvement in outcome
      after HSCT. Prospective clinical studies are therefore warranted to confirm these
      beneficial effects of fetal-maternal tolerance in allogeneic HSCT.

PMID- 16652219
TI  - ETS transcription factors and regulation of immunity.
AB  - The ETS family is a diverse group of transcription factors that control the
      expressions of genes that participate in an array of cellular activities, ranging
      from mitosis to apoptosis. As a consequence of regulating these processes, most
      ETS factors are oncogenic. However, there is growing evidence that ETS factors
      are also essential to regulation of the immune system. Of the 29 recognized ETS
      factors, nine are known to regulate genes involved in immunity, including Ets1,
      Ets2, GABP, Fli1, Elf1, MEF, ESE1, PU.1, and SpiB. These ETS factors typically
      activate the transcription of genes associated with pathogen and tumor defense,
      but several also demonstrate ability to repress transcription. Ets1 and PU.1
      appear to have the greatest impact on immunity, primarily through their control
      of immune cell development. Alterations of Fli1 and Elf1 expression are
      associated with autoimmunity, emphasizing the role of ETS factors as not only
      positive, but also negative regulators of immunity. This review summarizes the
      roles of ETS factors in development of the immune system, defense against
      pathogens and malignancies, and self-tolerance.

PMID- 16652220
TI  - Ubiquitous presence of beta-glucuronidase (GUS) in plants and its regulation in
      some model plants.
AB  - The enzyme beta-glucuronidase (GUS) is well characterized in animals and
      microbes. However, this enzyme is not well studied in plants and is widely
      assumed to be absent in them. In this study we document the ubiquitous presence
      of GUS in the model plants Arabidopsis thaliana, Oryza sativa, Nicotiana tabacum
      and Zea mays and record its expression pattern. The pH of the assay buffer was
      found to be critical with pH 4.0 being optimum for detection in all the species.
      GUS in plants appears to be associated with growth. In general, younger regions
      of the organs showed more GUS activity than the older and more mature tissues. In
      Brassica juncea roots stained for GUS, intense blue color could be seen in the
      trichoblast cells and the growing root hair cells as compared to the non-root
      hair forming epidermal cells or the fully elongated root hairs. Cotton fibers
      showed high GUS activity during the initial phase of elongation while the seed
      coat, from which the fibers formed, did not stain for GUS activity. The activity
      in the fibers disappeared after they were fully elongated. The level of GUS
      activity increased 2.58 folds in leaf tissues of N. tabacum when cultured in MS
      medium supplemented with 6-benzylaminopurine, while gibberellic acid enhanced GUS
      activity 2.9 folds in the inter-nodal regions of rice in 12-h treatment. In
      addition, elongation of stem, root and root hairs in tobacco seedlings was
      strongly inhibited by the specific inhibitor of GUS, saccharo-1-4-lactone in a
      reversible manner. Taken together, these evidences suggest a probable association
      of plant GUS in cell growth.

PMID- 16652221
TI  - Overexpression of the genes from thermophiles in Escherichia coli by high
      temperature cultivation.
AB  - Twenty-nine aminotransferase genes from Pyrococcus horikoshii, Aeropyrum pernix,
      and Sulfolobus tokodaii were cloned and expressed in Escherichia coli. The
      expression of several of the genes at 15, 25, or 37 degrees C resulted in the
      formation of insoluble protein aggregates. Therefore, we developed a simple
      method to express these genes into soluble proteins, by cultivating E. coli
      clones at a higher temperature. Thus, four genes could be expressed efficiently
      into soluble and active enzymes by cultivating the respective E. coli clones at
      46 degrees C. Subsequently, the method was applied to the expression into soluble
      proteins of other aminotransferase genes that were derived from nine species of
      thermophilic microorganisms.

PMID- 16652223
TI  - Long term effects of ketogenic diet in obese subjects with high cholesterol
      level.
AB  - OBJECTIVE: Various studies have convincingly shown the beneficial effect of
      ketogenic diet (in which the daily consumption of carbohydrate is less than 20
      grams, regardless of fat, protein and caloric intake) in reducing weight in obese
      subjects. However, its long term effect on obese subjects with high total
      cholesterol (as compared to obese subjects with normal cholesterol level is
      lacking. It is believed that ketogenic diet may have adverse effect on the lipid
      profile. Therefore, in this study the effect of ketogenic diet in obese subjects
      with high cholesterol level above 6 mmol/L is compared to those with
      normocholesterolemia for a period of 56 weeks. MATERIALS AND METHODS: In this
      study, 66 healthy obese subjects with body mass index (BMI) greater than 30,
      having high cholesterol level (Group I; n = 35) and those subjects with normal
      cholesterol level (Group II; n = 31) were selected. The body weight, body mass
      index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine,
      glucose and triglycerides were determined before and after the administration of
      the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32,
      40, 48 and 56 weeks of the treatment. RESULTS: The body weight and body mass
      index of both groups decreased significantly (P < 0.0001). The level of total
      cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased
      significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P <
      0.0001) after the treatment in both groups. CONCLUSION: This study shows the
      beneficial effects of ketogenic diet following its long term administration in
      obese subjects with a high level of total cholesterol. Moreover, this study
      demonstrates that low carbohydrate diet is safe to use for a longer period of
      time in obese subjects with a high total cholesterol level and those with
      normocholesterolemia.

PMID- 16652224
TI  - Effects of melatonin in reducing the toxic effects of doxorubicin.
AB  - Anthracycline antibiotics, such as doxorubicin and daunorubicin, constitute a
      group of wide spectrum therapeutic agents. Application of these drugs in
      chemotherapy is limited because of their toxic effects. Melatonin, the main
      secretory product of pineal gland, was recently found as a free radical scavenger
      and antioxidant. We decided to evaluate the tissue protective effect of melatonin
      against toxic effects of doxorubicin in six groups of rats. Rats were given
      doxorubicin (Dx) (45 mg/kg dose), melatonin (MEL) (10 mg/kg), first doxorubicin
      and then melatonin (DM), first melatonin and then doxorubicin (MD). The degree of
      kidney, lung, liver and brain cells' alterations were examined biochemically. In
      doxorubicin-treated group, malondialdehyde (MDA) levels of kidney, lung, liver
      and brain tissues were significantly increased but glutathione (GSH) levels were
      decreased compared to control rats. In the group in which first doxorubicin and
      then melatonin were given, MDA levels were significantly decreased compared to
      the doxorubicin-treated group. In doxorubicin-treated group, serum levels of
      creatinine, uric acid, blood urea nitrogen (BUN), Gamma-glutamyl transpeptidase
      (GGT) and Lactic acid dehydrogenase (LDH) were significantly increased while
      serum albumin and total protein levels were significantly decreased compared to
      control rats. Melatonin decreased the intensity of the changes produced by the
      administration of doxorubicin alone. Melatonin was quite efficient in reducing
      the formation of lipid peroxidation, restoring the tissue GSH contents and
      alterations of serum levels.

PMID- 16652225
TI  - Identification of elongation factor 1alpha as a potential associated binding
      partner for Akt2.
AB  - Akt protein kinase has been shown to play a pivotal role in diverse cell
      functions, including motility, apoptosis, growth and metabolism. How it
      differentially regulates these diverse functions is of significant interest.
      Three isoforms have been well characterized, Akt1, 2, and 3, encoded by separate
      genes, but showing high homology over the entire coding sequence (> 80%). An area
      of variability between the three isoforms is the C-terminal tail. To find
      potentially regulating binding partners of Akt2, the isoform implicated in
      metabolic control, we used a glutathione-S-transferase (GST) fusion protein
      expressing the C-terminal 75 residues of Akt2 (GST-Akt2 tail) to screen for
      proteins that specifically bound the Akt2 tail. Elongation factor 1alpha
      (EF1alpha) and beta-tubulin were identified as binding partners for the Akt2 tail
      by peptide mass fingerprinting. These two proteins have themselves been
      previously identified as interacting partners (Nakazawa et al.FEBS Lett. 453,29
      34, 1999). Using CHOT cells that overexpress insulin receptors and HA-tagged
      Akt2, we showed that EF1alpha co-immunoprecipitated with HA-tagged Akt2. It is
      thus possible that these proteins colocalise as part of a regulatory signaling
      complex with the cytoskeleton directing them to sites of cell activity.

PMID- 16652226
TI  - The action of extracellular NAD+ on gluconeogenesis in the perfused rat liver.
AB  - In the rat liver NAD+ infusion produces increases in portal perfusion pressure
      and glycogenolysis and transient inhibition of oxygen consumption. The aim of the
      present work was to investigate the possible action of this agent on
      gluconeogenesis using lactate as a gluconeogenic precursor. Hemoglobin-free rat
      liver perfusion in antegrade and retrograde modes was used with enzymatic
      determination of glucose production and polarographic assay of oxygen uptake.
      NAD+ infusion into the portal vein (antegrade perfusion) produced a concentration
      dependent (25-100 microM) transient inhibition of oxygen uptake and
      gluconeogenesis. For both parameters inhibition was followed by stimulation. NAD+
      infusion into the hepatic vein (retrograde perfusion) produced only transient
      stimulations. During Ca2+-free perfusion the action of NAD+ was restricted to
      small transient stimulations. Inhibitors of eicosanoid synthesis with different
      specificities (indo-methacin, nordihydroguaiaretic acid, bromophenacyl bromide)
      either inhibited or changed the action of NAD+. The action of NAD+ on
      gluconeogenesis is probably mediated by eicosanoids synthesized in non
      parenchymal cells. As in the fed state, in the fasted condition extracellular
      NAD+ is also able to exert two opposite effects, inhibition and stimulation.
      Since inhibition did not manifest significantly in retrograde perfusion it is
      likely that the generating signal is located in pre-sinusoidal regions.

PMID- 16652227
TI  - Expression of constitutive and inducible cytochrome P450 2E1 in rat brain.
AB  - Studies initiated to investigate the expression of cytochrome P450 2E1 (CYP2E1)
      in rat brain demonstrated low but detectable protein and mRNA expression in
      control rat brain. Though mRNA and protein expression of CYP2E1 in brain was
      several fold lower as compared to liver, relatively high activity of N
      nitrosodimethylamine demethylase (NDMA-d) was observed in control rat brain
      microsomes. Like liver, pretreatment with CYP2E1 inducers such as ethanol or
      pyrazole or acetone significantly increased the activity of brain microsomal NDMA
      d. Kinetic studies also showed an increase in the Vmax and affinity (Km) of the
      substrate towards the brain enzyme due to increased expression of CYP2E1 in
      microsomes of brain isolated from ethanol pretreated rats. In vitro studies using
      organic inhibitors, specific for CYP2E1 and anti-CYP2E1 significantly inhibited
      the brain NDMA-d activity indicating that like liver, NDMA-d activity in rat
      brain is catalyzed by CYP2E1. Olfactory lobes exhibited the highest CYP2E1
      expression and catalytic activity in control rats. Furthermore, several fold
      increase in the mRNA expression and activity of CYP2E1 in cerebellum and
      hippocampus while a relatively small increase in the olfactory lobes and no
      significant change in other brain regions following ethanol pretreatment have
      indicated that CYP2E1 induction maybe involved in selective sensitivity of these
      brain areas to ethanol induced free radical damage and neuronal degeneration.

PMID- 16652229
TI  - Novel heptamethine cyanine dyes with large Stoke's shift for biological
      applications in the near infrared.
AB  - A series of novel functionalized, water-soluble, pH-unsensitive, highly
      photostable heptamethine cyanine dyes (HCDs) has been synthesized. The aim of the
      synthesis was to obtain novel effective probes for fluorescence detection in the
      near infrared. Synthesis and characterization of a special HCD with large Stokes'
      shift (>100 nm), bioconjugation to IgG and effect of pH upon the new structure
      are presented.

PMID- 16652230
TI  - Matrix metalloproteinase-9 and autoimmune diseases.
AB  - Matrix metalloproteinases (also named matrixin or MMPs) are a major group of
      enzymes that regulate cell-matrix composition by using zinc for their proteolytic
      activities. They are essential for various normal biological processes such as
      embryonic development, morphogenesis, reproduction tissue resorption, and
      remodeling. Metalloproteinases also play a role in pathological processes
      including inflammation, arthritis, cardiovascular diseases, pulmonary diseases
      and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune
      diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic
      sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and
      atherosclerosis. MMP-9 plays either a primary or secondary role in each one of
      those autoimmune diseases by its up or down-regulation. It is not expressed
      constantly but rather is induced or suppressed by many regulating molecules. This
      feature of MMP-9 along with its involvement in disease pathogenesis turns it into
      a target for therapy of autoimmune diseases.

PMID- 16652236
TI  - Abnormal selective attention normalizes P3 amplitudes in PDD.
AB  - This paper studied whether abnormal P3 amplitudes in PDD are a corollary of
      abnormalities in ERP components related to selective attention in visual and
      auditory tasks. Furthermore, this study sought to clarify possible age
      differences in such abnormalities. Children with PDD showed smaller P3 amplitudes
      than controls, but no abnormalities in selective attention. Adolescents with PDD
      showed abnormal selective attention, as reflected by larger auditory Processing
      Negativity (PN) and visual N2b, but no P3 abnormalities. Dipole localizations
      revealed that the locations of PN generators in subjects with PDD differed from
      controls. It was concluded that the abnormalities in selective attention in
      adolescents with PDD have a normalizing effect on P3, and possibly act as a
      compensatory process.

PMID- 16652237
TI  - Physical activity patterns in youth with autism spectrum disorders.
AB  - The purpose of this study was to examine age-related physical activity patterns
      in youth with autism spectrum disorders (ASD). Thirty youth, aged 10-19 years,
      were divided into three groups: elementary (n=9), middle (n=9) and high (n=12)
      school. Participants wore an accelerometer and completed an activity
      questionnaire for seven consecutive days. The main findings were that (a)
      elementary youth are more active than the other groups, regardless type of day or
      time period, and (b) there are no consistent patterns in physical activity of
      youth with ASD according to day or time period. Findings emphasize that
      interventions for this population should address increasing extracurricular
      physical activity options during adolescence.

PMID- 16652248
TI  - Toxicity of dimethoate on primary productivity of a lentic aquatic ecosystem: a
      microcosm approach.

PMID- 16652249
TI  - Immunoassay method for the determination of pentachlorophenol in soil and
      sediment.

PMID- 16652250
TI  - Personal airborne asbestos exposure levels associated with various types of
      abatement.

PMID- 16652251
TI  - Effects of microbial and phosphate amendments on the bioavailability of lead (Pb)
      in shooting range soil.

PMID- 16652252
TI  - Persistence and transformation of thiamethoxam, a neonicotinoid insecticide, in
      soil of different agroclimatic zones of India.

PMID- 16652253
TI  - Persistence and dissipation of linuron (Afalon-50wp) in pea cropped soil and its
      effect on soil microorganisms.

PMID- 16652254
TI  - Dissipation of organophosphorus pesticides in green onion (Allium fistulosum L),
      cultivated in forced system called "barbacoas".

PMID- 16652255
TI  - Organochlorine pesticide (HCH and DDT) residues in dietary products from Shaanxi
      Province, People's Republic of China.

PMID- 16652256
TI  - Estimation of organochlorine pesticide residues in two popular spices extensively
      used as herbal tea ingredients in India.

PMID- 16652257
TI  - Trace metal content of snacks and appetizers consumed in Turkey.

PMID- 16652258
TI  - Distribution and source of polycyclic aromatic hydrocarbons (PAHs) on dust
      collected in Shanghai, People's Republic of China.

PMID- 16652259
TI  - Speciation of particle-associated resin acids and chromophoric compounds in water
      samples from the biological treatment system of two New Zealand pulp mills.

PMID- 16652260
TI  - Benzene, toluene, ethylbenzene, and isomeric xylenes in various water samples in
      Croatia.

PMID- 16652261
TI  - Pesticide residues in Rawal Lake, Islamabad, Pakistan.

PMID- 16652262
TI  - Leaching behavior and flux of toxic metals from chromated copper arsenate-treated
      wood and chromated copper arsenate-treated wood ash.

PMID- 16652263
TI  - Degradation of low and high molecular weight fractions of softwood bleachery
      effluents by Penicillium camemberti in up-flow column reactor.

PMID- 16652264
TI  - Evaluation of surface water pollution with atrazine, an endocrine disruptor
      chemical, in agricultural areas of Turopolje, Croatia.

PMID- 16652265
TI  - Accumulation of PCBs and organochlorine pesticides in river-caught European river
      lamprey (Lampetra fluviatillis) in Finland.

PMID- 16652266
TI  - Effects of the water soluble fraction of diesel fuel oil on some functional
      parameters of the neotropical freshwater fish Prochilodus lineatus Valenciennes.

PMID- 16652267
TI  - Chromium toxicity to Euglena gracilis strains depending on the physiocochemical
      properties of the culture medium.

PMID- 16652268
TI  - Copper kinetics and hepatic glutathione levels in the copper exposed frog Rana
      ridibunda after tetrathiomolybdate treatment.

PMID- 16652269
TI  - Accumulation of cadmium and lead in Cerastoderma glaucum originating from the
      Gulf of Gabes, Tunisia.

PMID- 16652270
TI  - Absorption of zinc and lead by Dittrichia viscosa grown in a contaminated soil
      amended with olive-derived wastes.

PMID- 16652271
TI  - Preexposure to copper modulates nonenzymatic antioxidants in liver of Channa
      punctata (Bloch) exposed to the herbicide paraquat.

PMID- 16652272
TI  - Impact of age of immature Dendrobaena octaedra (Sav.), (Lumbricidae: Oligochaeta)
      at cadmium application on life history response.

PMID- 16652273
TI  - A persistent(ly) enigmatic ecological mystery: bacterial vaginosis.

PMID- 16652274
TI  - High recurrence rates of bacterial vaginosis over the course of 12 months after
      oral metronidazole therapy and factors associated with recurrence.
AB  - BACKGROUND: We wished to determine recurrences of bacterial vaginosis (BV) after
      treatment over the course of 12 months and to establish factors associated with
      recurrence. METHODS: Women with symptomatic BV (a Nugent score [NS] of 7-10 or of
      4-6 with >or=3 Amsel criteria) were enrolled. BV was treated with 400 mg of oral
      metronidazole twice a day for 7 days. Participants completed a questionnaire and
      vaginal swabs were collected at 1, 3, 6, and 12 months; the study end point was
      an NS of 7-10. RESULTS: A total of 121 (87%) women with an NS of 7-10 and 18
      (13%) with an NS of 4-6 and >or=3 Amsel criteria were enrolled; 130 (94%)
      returned >or=1 vaginal samples. Sixty-eight women (58% [95% confidence interval
      {CI}, 49%-66%]) had a recurrence of BV (NS 7-10), and 84 (69% [95% CI, 61%-77%])
      had a recurrence of abnormal vaginal flora (NS 4-10) by 12 months. A past history
      of BV, a regular sex partner throughout the study, and female sex partners were
      significantly associated with recurrence of BV and abnormal vaginal flora by
      multivariate analysis; the use of hormonal contraception had a negative
      association with recurrence. CONCLUSION: Current recommended treatment is not
      preventing the recurrence of BV or abnormal vaginal flora in the majority of
      women; factors associated with recurrence support a possible role for sexual
      transmission in the pathogenesis of recurrent BV.

PMID- 16652275
TI  - Indirect effect of conjugate vaccine on adult carriage of Streptococcus
      pneumoniae: an explanation of trends in invasive pneumococcal disease.
AB  - BACKGROUND: Use of heptavalent protein-polysaccharide pneumococcal conjugate
      vaccine (PCV7) has been associated with decreases in PCV7-type invasive
      pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use
      has also indirectly decreased the rate of invasive disease in adults, presumably
      through decreased transmission of pneumococci from vaccinated children to adults.
      METHODS: We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004.
      Streptococcus pneumoniae isolates were characterized by serotype and
      antimicrobial susceptibility. We analyzed trends in serotype distribution,
      antibiotic resistance, and factors associated with adult carriage of PCV7
      serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS:
      We collected 15,598 NP swabs; overall, 52% of adults living in the villages
      surveyed participated in the colonization study. The proportion of adult carriers
      with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000
      to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing
      isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6%
      in 2004 (P=.05), whereas the percentage of isolates with intermediate
      susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004
      (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived
      with a child <5 years old or if they lived with a child who had not been age
      appropriately vaccinated with PCV7. CONCLUSIONS: Pediatric vaccination with PCV7
      has resulted in decreased PCV7-type pneumococcal carriage among adults and helps
      to explain recent decreases in the rate of PCV7-type invasive pneumococcal
      disease among adults.

PMID- 16652276
TI  - Roles of 34 virulence genes in the evolution of hospital- and community
      associated strains of methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: The extent to which the horizontal transfer of virulence genes has
      contributed to the emergence of contemporary virulent strains of methicillin
      resistant Staphylococcus aureus (MRSA) in hospital and community settings is
      poorly understood. METHODS: Epidemiologically well-characterized MRSA isolates
      collected over 8.5 years were genotyped and tested for the presence of 34
      virulence genes. RESULTS: Six strain types accounted for 88.2% of all MRSA
      infections. The evolution of contemporary hospital and community phenotypes
      within the CC8 and CC30 lineages--2 background genomes that produced historical
      pandemic MRSA clones--were associated with multiple horizontal acquisitions of
      virulence genes. The epidemic community phenotype of a CC8 strain, designated
      ST8:USA300, was linked to the acquisition of staphylococcal cassette chromosome
      (SCC)mec type IV, the genes for Panton-Valentine leukocidin (PVL), and the
      enterotoxin Q and K genes. Similarly, the epidemic community phenotype of a CC30
      strain, ST30:USA1100, was linked to the acquisition of SCCmec type IV and the pvl
      genes. In contrast, the epidemic hospital phenotype of another CC30 strain,
      ST36:USA200, was associated with the acquisition of SCCmec type II, the
      enterotoxin A gene, and the toxic shock syndrome toxin 1 gene. The pvl genes
      appear not to be essential for the evolution OF other community-associated
      strains of mrsa, including ST8:USA500 and ST59:USA1000. CONCLUSIONS: The
      horizontal transfer of virulence genes, although infrequent, is epidemiologically
      associated with the emergence of new virulent strains of MRSA.

PMID- 16652277
TI  - Revisiting the role of neutralizing antibodies in mother-to-child transmission of
      HIV-1.
AB  - We analyzed the association between mother-to-child transmission (MTCT) of human
      immunodeficiency virus type 1 (HIV-1) and maternal neutralizing antibodies to
      heterologous primary isolates of various HIV-1 clades, to test the hypothesis
      that protective antibodies are those with broad neutralizing activity. Our study
      sample included 90 Thai women for whom the timing of HIV-1 transmission (in utero
      or intrapartum) was known. The statistical analysis included a conditional
      logistic-regression model to control for both plasma viral load and duration of
      zidovudine prophylaxis. The higher the titer of neutralizing antibodies to a
      heterologous strain of the same clade, the lower the rate of MTCT of HIV-1. More
      specifically, high levels of neutralizing antibodies to the MBA (CRF01_AE) strain
      were associated with low intrapartum transmission of HIV-1. This suggested that
      such heterologous neutralizing antibodies may be involved in the natural
      prevention of late perinatal HIV transmission. These data are consistent with the
      hypothesis that the use of some antibodies might help to prevent perinatal HIV
      transmission, through passive immunoprophylaxis. Moreover, the study of humoral
      factors associated with MTCT of HIV-1 may identify correlates of protection that
      should help in the design of efficient HIV/acquired immunodeficiency syndrome
      vaccines.

PMID- 16652278
TI  - Association between the replication capacity and mother-to-child transmission of
      HIV-1, in antiretroviral drug-naive Malawian women.
AB  - Replication capacity and transmission of human immunodeficiency virus (HIV)-1 in
      antiretroviral drug-naive Malawian women who had subtype C infection were
      investigated. Infant children of these women received either 1 dose of nevirapine
      or 1 dose of nevirapine plus 1 week of daily doses of zidovudine. PhenoSense HIV
      was used to determine replication capacity in 49 women whose infants were
      infected with HIV-1 and in 47 women whose infants were uninfected by 6-8 weeks of
      age. Mean replication capacity was higher in transmitters than in nontransmitters
      (P=.01). In a multivariate model, higher replication capacity was associated with
      transmission (odds ratio, 1.45 for each 10% increase in replication capacity [95%
      confidence interval, 1.11-1.90]; P = .0063), after adjustment for maternal HIV-1
      load and other factors.

PMID- 16652279
TI  - Lopinavir-ritonavir: effects on endothelial cell function in healthy subjects.
AB  - To differentiate between the effects that antiretroviral drugs have on the
      endothelium and the secondary effects that they have on immune function, viral
      load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human
      subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of
      forearm blood flow, the treatment's effects on endothelial cell function were
      measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm
      blood-flow responses to the endothelium-dependent vasodilator, acetylcholine,
      increased significantly (P=.03), and forearm blood flow decreased to a greater
      extent during specific inhibition of NO synthase by N(G)-monomethyl-L-arginine.
      Thus, in this small cohort of subjects, short-term treatment with lopinavir
      ritonavir does not appear to directly promote endothelial cell dysfunction.

PMID- 16652280
TI  - Cytokine modulation of the innate immune response in feline immunodeficiency
      virus-infected cats.
AB  - BACKGROUND: In vitro data suggest that innate immune function in human
      immunodeficiency virus type 1-infected patients is compromised; however, in vivo
      studies are lacking. Feline immunodeficiency virus (FIV) infection in cats
      provides an excellent model to explore innate immune function in vivo. The innate
      response against Listeria monocytogenes is well understood, making it a useful
      immune probe. METHODS: Recombinant L. monocytogenes carrying eukaryotic
      expression plasmids for feline tumor necrosis factor (TNF)- alpha , interleukin
      (IL)-10, interferon (IFN)- gamma , and IL-15 were created to determine whether
      specific cytokines would modulate innate immune function. L. monocytogenes was
      delivered subcutaneously, and local lymph nodes were evaluated for size, cell
      subpopulations, and L. monocytogenes burden. Two months later, memory responses
      were evaluated by IFN- gamma enzyme-linked immunospot assay. RESULTS: FIV
      positive cats had significantly less lymph-node enlargement and a greater L.
      monocytogenes burden than FIV-negative control cats. TNF- alpha improved
      listericidal activity in FIV-negative control cats but not in FIV-positive cats,
      whereas IL-10 modestly reduced function in FIV-negative control cats. IFN- gamma
      improved memory responses but not clearance of L. monocytogenes. IL-15 improved
      innate function in FIV-positive cats and increased the percentage of natural
      killer cells. CONCLUSIONS: Lentivirus infection impairs innate immune function in
      vivo, and IL-15 can significantly restore function. We hypothesize that altered
      dendritic-cell function and increased regulatory T cell activity may underlie the
      innate immune defect in HIV infection.

PMID- 16652281
TI  - Long-term protection against carriage of hepatitis B virus after infant
      vaccination.
AB  - BACKGROUND: Carriage of hepatitis B virus (HBV) is a major risk factor for liver
      cirrhosis and hepatocellular carcinoma. Infant vaccination has been effective in
      preventing horizontal transmission during early childhood. It is unknown whether
      protection is maintained into early adulthood. METHODS: In 1984, early childhood
      vaccination was introduced in 2 rural Gambian villages. In 2003, serological
      assessment of 81.5% of 1,350 eligible participants 1-24 years old was done, to
      determine vaccine efficacy against infection and carriage. RESULTS: Overall
      vaccine efficacy against infection and carriage was 83.4% (95% confidence
      interval [CI], 79.8%-86.6%) and 96.5% (85% CI, 93.9%-98.9%), respectively.
      Vaccine efficacy against infection was similar when restricted to primary
      responders (85.3%), but a significant effect of peak antibody concentration was
      found. Both vaccine efficacy and levels of hepatitis B surface antibody (anti
      HBs) decreased with age, resulting in a vaccine efficacy against infection and
      carriage among 20-24-year-old participants of 70.9% (95% CI, 60.4%-80.5%) and
      91.1% (95% CI, 75.8%-100%), respectively. Fifteen years after vaccination, fewer
      than half of the vaccinees had detectable anti-HBs. The prevalence of carriage in
      the unvaccinated population was similar to the prevalence 20 years earlier.
      CONCLUSIONS: HBV vaccination early during life can provide long-lasting
      protection against carriage, despite decreasing antibody levels. The role played
      by subclinical boosting and the necessity of a booster need to be evaluated.

PMID- 16652282
TI  - The relationship of rhinovirus-associated asthma hospitalizations with inhaled
      corticosteroids and smoking.
AB  - BACKGROUND: Although rhinovirus (RV) respiratory infections trigger asthma
      exacerbations, the etiologic association between this virus and severe
      exacerbations, as well as the clinical characteristics of adults at risk for RV
      associated asthma that necessitates hospitalization, have not been established.
      METHODS: During 1999-2003, we conducted a cohort study of 101 adults
      prospectively enrolled at hospital admission for an asthma exacerbation. Patient
      characteristics and frequencies of RV in nasal specimens were analyzed, by
      reverse-transcription polymerase chain reaction (RT-PCR), at asthma-related
      hospital admission and at a 3-month convalescent follow-up visit. RESULTS: RV was
      detected by RT-PCR in 21% of hospitalized patients over a 4-year period and in
      1.3% of patients who returned for a 3-month follow-up visit. RV detection was
      strongly associated with hospitalization for asthma (adjusted odds ratio [OR],
      15.1 [95% confidence interval {CI}, 1.88-121.4]). After adjustment for baseline
      asthma severity, RV-positive patients were more likely than RV-negative patients
      to be current smokers and nonusers of inhaled corticosteroids (ICSs) (adjusted
      OR, 11.18 [95% CI, 2.37-52.81]; P=.002). CONCLUSIONS: RV respiratory infection is
      an etiologic agent in severe asthma exacerbations necessitating hospitalization
      in adults. Compared with hospitalized patients with asthma who were RV negative,
      RV-positive patients were significantly more likely to be smokers and nonusers of
      ICSs.

PMID- 16652283
TI  - The impact of infection with human metapneumovirus and other respiratory viruses
      in young infants and children at high risk for severe pulmonary disease.
AB  - We conducted a prospective, observational study to characterize the clinical
      manifestations of respiratory infections caused by human metapneumovirus (hMPV)
      and other viruses in 194 premature infants and young children with chronic lung
      disease or congenital heart disease in Buenos Aires. Children had 567 episodes of
      respiratory illness and were monitored until they were 2 years old or until the
      completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of
      moderate or greater severity. Human parainfluenza virus type 3 caused 24
      infections (4%), and 5 (25%) of 20 lung infections led to hospitalization.
      Respiratory syncytial virus (RSV) caused 33 episodes--17% of infections and 32%
      of hospitalizations during the respiratory season. None of the 10 children
      infected with influenza virus had severe disease. The present study of at-risk
      children suggests that hMPV and influenza virus are infrequent agents of severe
      disease and highlights the need for preventive interventions against RSV in
      developing countries.

PMID- 16652284
TI  - Kinetics of US28 gene expression during active human cytomegalovirus infection in
      lung-transplant recipients.
AB  - Targeting viral proteins early during infection may limit exacerbation of human
      cytomegalovirus infection. The viral chemokine-receptor homologue US28 interferes
      with leukocyte trafficking and, possibly, viral replication. Because US28
      molecules are abundant on the surface of infected cells, this homologue is a
      potential target for antiviral therapy. To assess the relationship between US28
      and disease activity, we measured, by quantitative reverse-transcription
      polymerase chain reaction, the levels of US28 and immediate-early (IE) 1 gene
      transcripts in the blood of lung-transplant recipients. We found that, during
      primary and secondary infection, the IE1 and US28 genes have early transcription
      kinetics and are expressed at similar levels. This may render US28 an attractive
      target for antiviral therapy.

PMID- 16652285
TI  - Reduced Foxp3 protein expression is associated with inflammatory disease during
      human t lymphotropic virus type 1 Infection.
AB  - The Foxp3 protein is a specific marker of CD4(+)CD25(+) regulatory T (T(reg))
      cells, and its expression is critical to their development and function. Several
      studies have demonstrated the dysregulation of Foxp3 expression during human
      inflammatory diseases. Infection with human T lymphotropic virus type 1 (HTLV-1)
      is associated with the development of a number of inflammatory conditions,
      including myelopathy, although the majority of individuals who are infected with
      HTLV-1 remain asymptomatic. To examine the role played by T(reg) cells in the
      development of inflammatory disease during HTLV-1 infection, we examined Foxp3
      expression by flow cytometry. Our analysis showed that HTLV-1-associated
      myelopathy/tropical spastic paraparesis was associated with a lower expression
      (compared with that in asymptomatic HTLV-1 carriers and healthy donors) of Foxp3
      in peripheral-blood leukocytes. In individuals infected with HTLV-1, Foxp3
      expression was inversely correlated with HTLV-1 tax proviral DNA load. These
      results suggest that impaired Foxp3 expression may contribute to the development
      of inflammatory disease during HTLV-1 infection.

PMID- 16652286
TI  - Virulence of malaria is associated with differential expression of Plasmodium
      falciparum var gene subgroups in a case-control study.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major
      pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is
      encoded by approximately 60 var genes per haploid genome. Most var genes are
      grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific
      expression of these subgroups has clinical significance. Using field samples from
      children from Papua New Guinea with severe, mild, and asymptomatic malaria, we
      compared proportions of transcripts of var groups, as determined by quantitative
      polymerase chain reaction. We found a significantly higher proportion of var
      group B transcripts in children with clinical malaria (mild and severe), whereas
      a large proportion of var group C transcripts was found in asymptomatic children.
      These data from naturally infected children clearly show that major differences
      exist in var gene expression between parasites causing clinical disease and those
      causing asymptomatic infections. Furthermore, parasites forming rosettes showed a
      significant up-regulation of var group A transcripts.

PMID- 16652287
TI  - Interferon-gamma and nitric oxide in combination with antibodies are key
      protective host immune factors during trypanosoma congolense Tc13 Infections.
AB  - The control of chronic Trypanosoma congolense trypanosomiasis was analyzed using
      several gene-deficient mouse strains. First, interferon (IFN)-gamma receptor (IFN
      gamma-R)-deficient mice were used to show that IFN- gamma -mediated immune
      activation is crucial for parasitemia control. Second, infections in major
      histocompatibility complex (MHC) class II-deficient mice indicate that this
      molecule is needed for initiation of IFN- gamma and subsequent tumor necrosis
      factor (TNF) production. Downstream of IFN-gamma-R signaling, inducible NO
      synthase (iNOS)-dependent trypanosome killing occurs, as is shown by the
      hypersusceptible phenotype of iNOS-deficient mice. Besides proinflammatory
      responses, B cells and, more specifically, immunoglobulin (Ig) G antibodies are
      crucial for parasite killing. Hence, parasitemia control is abolished in B cell
      deficient mice, whereas IgM-deficient mice control the infection as efficiently
      as do wild-type mice. In addition, splenectomized mice that have a normal IgM
      response but an impaired IgG2a/3 response fail to control T. congolense
      infection. Collectively, these results suggest that host protective immunity
      against T. congolense is critically dependent on the combined action of the
      proinflammatory mediators/effectors IFN- gamma , TNF, and NO and antiparasite
      IgGs.

PMID- 16652288
TI  - Chemokine CC receptor 2 is important for acute control of cardiac parasitism but
      does not contribute to cardiac inflammation after infection with Trypanosoma
      cruzi.
AB  - The CC chemokine ligand 2 (CCL2) and CC chemokine receptor 2 (CCR2) are expressed
      in the heart after infection with Trypanosoma cruzi, suggesting that they play an
      important role in host defense. Infection of CCR2-deficient (CCR2(-/-)) mice with
      T. cruzi resulted in increased cardiac parasitism, yet the severity of cardiac
      inflammation was not affected. In addition, expression of interferon- gamma and
      inducible NO synthase in the heart, which are associated with effective killing
      of trypomastigotes, was not affected in CCR2(-/-) mice. These observations reveal
      that CCR2 signaling plays a distinct role that is separate from that of
      influencing either chemotaxis or previously defined anti-trypomastigote
      mechanisms for the control of T. cruzi's replication in the heart.

PMID- 16652289
TI  - Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo.
AB  - Mannan-binding lectin (MBL) is a component of the innate immune system. The goal
      of the present study was to evaluate binding of MBL to Candida albicans in vitro
      and in vivo and to assess the impact of MBL treatment on host resistance. The
      results showed a variable and often discontinuous pattern of binding to
      individual yeast cells. MBL bound to cells grown at 37 degrees C but not to cells
      grown at 23 degrees C. The putative MBL ligand was constitutively present on
      yeast cells grown at 23 degrees C, but the ligand was masked on such cells, such
      that MBL could not bind. C. albicans yeasts and hyphae in infected tissue bound
      MBL. Finally, parenteral administration of MBL increased resistance of mice to
      hematogenously disseminated candidiasis. These results suggest that MBL is an
      important component of innate resistance to candidiasis and that MBL therapy may
      be a means to prevent disseminated candidiasis in high-risk patients.

PMID- 16652290
TI  - Predominant influence of environmental determinants on the persistence and
      avidity maturation of antibody responses to vaccines in infants.
AB  - BACKGROUND: Immune responses are complex traits influenced by genetic and
      environmental factors. We previously reported that genetic factors control early
      antibody responses to vaccines in Gambian infants. For the present study, we
      evaluated the determinants of the memory phase of immunoglobulin G (IgG)
      responses. METHODS: Antibody responses to tetanus toxoid (TT), measles vaccines,
      and environmental antigens (total IgG levels) were measured in 210 Gambian twin
      pairs recruited at birth. Intrapair correlations for monozygous and dizygous
      pairs were compared to estimate the environmental and genetic components of
      variations in response. RESULTS: In contrast to antibody responses measured in
      infants at age 5 months, 1 month after immunization, no significant contribution
      of genetic factors to anti-TT antibody and total IgG levels was detected at age
      12 months. Genetic factors controlled measles antibody responses in 12-month-old
      infants, which indicates that the increasing influence of environmental
      determinants on anti-TT responses was not related to the older age of the
      children but, rather, to the time elapsed since immunization. Environmental
      factors also predominantly controlled affinity maturation and the production of
      high-avidity antibodies to TT. CONCLUSIONS: Genetic determinants control the
      early phase of the vaccine antibody response in Gambian infants, whereas
      environmental determinants predominantly influence antibody persistence and
      avidity maturation.

PMID- 16652291
TI  - Interferon-gamma-mediated antiviral immunity against orthopoxvirus infection is
      provided by gamma delta T cells.

PMID- 16652293
TI  - Single-dose sulfadoxine-pyrimethamine in intermittent preventive treatment of
      malaria.

PMID- 16652295
TI  - Gilbert syndrome and the development of antiretroviral therapy-associated
      hyperbilirubinemia: genetic screening is unnecessary.

PMID- 16652298
TI  - Heterosubtypic immunity to influenza: right hypothesis, wrong comparison.

PMID- 16652299
TI  - Excretion of oral poliovirus vaccine strains: effect of vaccination schedule.

PMID- 16652300
TI  - Early detection of perinatal tuberculosis using a whole blood interferon-gamma
      release assay.
AB  - BACKGROUND: The diagnosis of perinatal tuberculosis (TB) is problematic because
      of its nonspecific presentation, the difficulty of obtaining microbiological
      confirmation, and the unreliability of the tuberculin skin test. Immunodiagnosis
      of TB has received new attention with the discovery of Mycobacterium tuberculosis
      specific immunodominant antigens (early secreted antigenic target 6 [ESAT-6] and
      culture filtrate protein 10 [CFP-10]) that are encoded by the RD1 region of the
      pathogen. A whole blood assay has recently been developed to quantitatively
      measure interferon- gamma production by lymphocytes specific to these antigens,
      but its evaluation in the diagnosis of TB in infants and children has been
      limited to date. METHODS: In addition to routine diagnostic evaluation
      (tuberculin skin tests, culture of early-morning gastric aspirate samples, and
      chest radiographs), 2 infants with suspected perinatal TB were investigated with
      a whole blood interferon-gamma release assay. RESULTS: The results of the
      tuberculin skin tests were negative for both patients. The findings of the chest
      radiographs were abnormal with features suggestive of miliary TB. A whole blood
      interferon- gamma release assay was performed and yielded positive results within
      48 h after admission to the hospital for both patients, prompting early
      antituberculous treatment. M. tuberculosis was cultured after 6 weeks from
      gastric aspirate samples collected on admission to the hospital from both
      infants. At 6 months of age, both infants were thriving and had acheived normal
      developmental milestones. CONCLUSIONS: The advent of interferon- gamma release
      assays may prove to be useful in the evaluation of infants with suspected
      perinatal TB.

PMID- 16652301
TI  - Against all odds: molecular confirmation of an implausible case of bone
      tuberculosis.
AB  - We report the use of typing based on a variable number of tandem repeats of
      genetic elements called "mycobacterial interspersed repetitive units" to clarify
      a puzzling situation involving a patient with an exceptional case of
      spondylodiskitis that initially led to the suspicion of a possible event of
      laboratory cross-contamination with Mycobacterium tuberculosis.

PMID- 16652302
TI  - HIV type 2 demyelinating encephalomyelitis.
AB  - A human immunodeficiency virus (HIV) type 2 (HIV-2)-infected African patient
      developed inflammatory demyelinating lesions of the optic nerves, spinal cord,
      and brain, which coincided with a decreasing CD4 cell count and with active HIV-2
      replication. This case provides evidence that HIV-2 is neurotropic, extends the
      range of known HIV-2-associated neurological complications, and confirms the
      overlap between the neurological complications of HIV type 1 and HIV-2 infection.

PMID- 16652303
TI  - Deep-seated resistance in relapsed paratyphoid fever.
AB  - We describe a case of relapsed paratyphoid fever in which the isolate had reduced
      susceptibility to ciprofloxacin due to a rare mutation within the gyrA gene.
      18fluorodeoxyglucose positron emission tomography scanning identified deep-seated
      infection including unsuspected aortitis and highlights the utility of novel
      imaging techniques to improve our understanding and treatment of this disease.

PMID- 16652304
TI  - In vivo development of ertapenem resistance in a patient with pneumonia caused by
      Klebsiella pneumoniae with an extended-spectrum beta-lactamase.
AB  - Four sequential extended-spectrum beta -lactamase-producing isolates of
      Klebsiella pneumoniae were obtained from a patient after treatment with ertapenem
      and cultured. The first and fourth isolates were susceptible to ertapenem,
      whereas the second and third were resistant. All 4 isolates belonged to the same
      strain and produced a group 1 CTX-M enzyme; additionally, the resistant isolates
      had lost a porin.

PMID- 16652305
TI  - Apparent absence of Pneumocystis jirovecii in healthy subjects.
AB  - We prospectively investigated 30 healthy subjects with normal CD4+ T cell counts
      in blood and normal findings of spirometry and chest radiography for the presence
      of Pneumocystis jirovecii, by performing polymerase chain reaction on sputum
      specimens. Fifty patients with chronic obstructive pulmonary disease were
      investigated at the same time in the same manner; this group was used as controls
      for the diagnosis of pulmonary colonization with P. jirovecii. None of the
      healthy subjects had positive test results, whereas the fungus was detected in 8
      patients with chronic obstructive pulmonary disease. The results suggest that in
      our region (Amiens, France), P. jirovecii is apparently uncommon in healthy
      subjects and that this population, therefore, plays a minor role in circulation
      of the fungus within human communities.

PMID- 16652306
TI  - Outbreak of enterotoxigenic Escherichia coli infection with an unusually long
      duration of illness.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is an emerging cause of
      foodborne outbreaks of infection in the United States, yet its epidemiology is
      not completely understood. METHODS: In September 2004, we investigated an
      outbreak of infection due to ETEC at an Illinois corporation following a meal
      served to approximately 700 employees. Clinical samples were negative for enteric
      pathogens and were tested for ETEC using stool culture and polymerase chain
      reaction (PCR). An environmental investigation was conducted to determine whether
      food-service practices or conditions led to this outbreak. A case of illness
      caused by ETEC was defined as onset of diarrhea and > or =1 of the following
      symptoms during 23-30 September 2004: cramps, vomiting, nausea, headache, or
      weight loss. RESULTS: The 111 ill employees interviewed had only 1 meal in
      common. Cucumber salad and noodle salad from that meal were associated with
      illness; no food was available for testing. A PCR test for ETEC in stool was
      positive in samples from 6 of 11 patients; 3 ETEC serotypes were detected. The
      environmental investigation revealed no critical violations. The median duration
      of diarrhea (7 days) was longer than that observed for the majority of outbreaks
      of ETEC infection (4 days) and was associated with consumption of carbonated
      beverages (odds ratio, 4.5; 95% confidence interval, 2.0-10.3). CONCLUSIONS:
      Emerging features of ETEC identified in this outbreak include the organism's role
      in domestic outbreaks and its ability to cause prolonged diarrheal illness.
      Additionally, integrating the results of nonculture-based diagnostic techniques
      into foodborne outbreak surveillance presents challenges under the current
      guidelines of the Centers for Disease Control and Prevention.

PMID- 16652307
TI  - Enterotoxigenic Escherichia coli: outbreak surveillance and molecular testing.

PMID- 16652308
TI  - Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus
      hemorrhagic fever in the Republic of Congo.
AB  - BACKGROUND: Patients who have refused to provide blood samples has meant that
      there have been significant delays in confirming outbreaks of Ebola virus
      hemorrhagic fever (EVHF). During the 2 EVHF outbreaks in the Republic of Congo in
      2003, we assessed the use of oral fluid specimens versus serum samples for
      laboratory confirmation of cases of EVHF. METHODS: Serum and oral fluid specimens
      were obtained from 24 patients with suspected Ebola and 10 healthy control
      subjects. Specimens were analyzed for immunoglobulin G antibodies by enzyme
      linked immunosorbent assay (ELISA) and for Ebola virus by antigen detection ELISA
      and reverse-transcriptase polymerase chain reaction (RT-PCR). Oral fluid
      specimens were collected with a commercially available collection device.
      RESULTS: We failed to detect antibodies against Ebola in the oral fluid specimens
      obtained from patients whose serum samples were seropositive. All patients with
      positive serum RT-PCR results also had positive results for their oral fluid
      specimens. CONCLUSIONS: This study demonstrates the usefulness of oral fluid
      samples for the investigation of Ebola outbreaks, but further development in
      antibodies and antigen detection in oral fluid specimens is needed before these
      samples are used for filovirus surveillance activities in Africa.

PMID- 16652309
TI  - Fatal hemorrhagic fever caused by West Nile virus in the United States.
AB  - BACKGROUND: Most West Nile virus (WNV) infections in humans are asymptomatic;
      severe disease occurs in relatively few patients and typically manifests as
      encephalitis, meningitis, or acute flaccid paralysis. A few cases of life
      threatening disease with diffuse hemorrhagic manifestations have been reported in
      Africa; however, this clinical presentation has not been documented for any of
      the >16,700 cases of WNV disease reported in the United States during 1999-2004.
      We describe a case of fulminant WNV infection in a 59-year-old Florida man who
      died following a brief illness that resembled hemorrhagic disease caused by
      Rickettsia reckettsii, dengue virus or yellow fever virus. METHODS: Traditional
      and contemporary diagnostic assays, including culture isolation, electron
      microscopic examination, reverse-transcriptase polymerase chain reaction
      amplification, and immunohistochemical stains, were used to confirm systemic WNV
      infection in the patient. RESULTS: WNV was isolated in a cell culture from a skin
      biopsy specimen obtained from the patient shortly prior to death. Electron
      microscopic examination identified the isolate as a flavivirus, and reverse
      transcriptase polymerase chain reaction amplified specific WNV sequences from the
      isolate and patient tissue. Quantitative polymerase chain reaction identified
      approximately 1x10(7) viral copies/mL in the patient's serum. WNV antigens were
      detected by immunohistochemical stains in intravascular mononuclear cells and
      endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central
      nervous system; no viral antigens were identified in neurons or glial cells of
      the central nervous system. CONCLUSIONS: Although hemorrhagic disease is a rare
      manifestation of WNV infection, the findings provided by this report may offer
      new insights regarding the clinical spectrum and pathogenesis of WNV disease in
      humans.

PMID- 16652310
TI  - Clinical and virological improvement of hepatitis B virus-related or hepatitis C
      virus-related chronic hepatitis with concomitant hepatitis A virus infection.
AB  - BACKGROUND: We evaluated the clinical and virological characteristics of
      hepatitis A virus infection in persons concomitantly infected with hepatitis B
      virus (HBV) or hepatitis C virus (HCV). METHODS: We enrolled 21 patients with
      acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13
      patients who were positive for hepatitis B surface antigen (case B group), 8
      patients who were anti-HCV positive (case C group), and 21 patients with acute
      hepatitis A without a preexisting liver disease (control A group). Two control
      groups of patients with chronic hepatitis B (control B group) or C (control C
      group) were also chosen. All control groups were pair-matched by age and sex with
      the corresponding case group. RESULTS: Fulminant hepatitis A was never observed,
      and hepatitis A had a severe course in 1 patient in the case B group and in 1
      patient in the control A group. Both patients recovered. On admission, HBV DNA
      was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in
      the control B group; HCV RNA was found in no patient in the case C group and in
      16 patients (81.2%) in the control C group. Of 9 patients in the case B group who
      were followed up for 6 months, 3 became negative for hepatitis B surface antigen
      and positive for hepatitis B surface antibody, 2 remained positive for hepatitis
      B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA
      with a low viral load [corrected] Of 6 patients in the case C group who were
      followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently
      low viral loads. CONCLUSION: Concomitant hepatitis A was always self-limited,
      associated with a marked inhibition of HBV and HCV genomes, and possibly had a
      good prognosis for the underlying chronic hepatitis.

PMID- 16652311
TI  - Reduction of urinary tract infection and antibiotic use after surgery: a
      controlled, prospective, before-after intervention study.
AB  - BACKGROUND: Urinary tract infection is the most frequent health care-associated
      complication. We hypothesized that the implementation of a multifaceted
      prevention strategy could decrease its incidence after surgery. METHODS: In a
      controlled, prospective, before-after intervention trial with 1328 adult patients
      scheduled for orthopedic or abdominal surgery, nosocomial infection surveillance
      was conducted until hospital discharge. A multifaceted intervention including
      specifically tailored, locally developed guidelines for the prevention of urinary
      tract infection was implemented for orthopedic surgery patients, and abdominal
      surgery patients served as control subjects. Infectious and noninfectious
      complications, adherence to guidelines, and antibiotic use were monitored before
      and after the intervention and again 2 years later. RESULTS: The incidence of
      urinary tract infection decreased from 10.4 to 3.9 episodes per 100 patients in
      the intervention group (incidence-density ratio, 0.41; 95% CI, 0.20-0.79;
      P=.004). Adherence to guidelines was 82.2%. Both the frequency and the duration
      of urinary catheterization decreased following the intervention. Recourse to
      antibiotic therapy after surgery dropped in the intervention group from 17.9 to
      15.6 defined daily doses per 100 patient-days (P<.005) because of a reduced need
      for the treatment of urinary tract infection (P<.001). Follow-up after 2 years
      revealed a sustained impact of the strategy and a subsequent low use of
      antibiotics, consistent with stable adherence to guidelines (80.8%). CONCLUSIONS:
      A multifaceted prevention strategy can dramatically decrease postoperative
      urinary tract infection and contribute to the reduction of the overall use of
      antibiotics after surgery.

PMID- 16652312
TI  - Reduction in acquisition of vancomycin-resistant enterococcus after enforcement
      of routine environmental cleaning measures.
AB  - BACKGROUND: The role of environmental contamination in nosocomial cross
      transmission of antibiotic-resistant bacteria has been unresolved. Using
      vancomycin-resistant enterococci (VRE) as a marker organism, we investigated the
      effects of improved environmental cleaning with and without promotion of hand
      hygiene adherence on the spread of VRE in a medical intensive care unit. METHODS:
      The study comprised a baseline period (period 1), a period of educational
      intervention to improve environmental cleaning (period 2), a "washout" period
      without any specific intervention (period 3), and a period of multimodal hand
      hygiene intervention (period 4). We performed cultures for VRE of rectal swab
      samples obtained from patients at admission to the intensive care unit and daily
      thereafter, and we performed cultures of environmental samples and samples from
      the hands of health care workers twice weekly. We measured patient clinical and
      demographic variables and monitored intervention adherence frequently. RESULTS:
      Our study included 748 admissions to the intensive care unit over a 9-month
      period. VRE acquisition rates were 33.47 cases per 1000 patient-days at risk for
      period 1 and 16.84, 12.09, and 10.40 cases per 1000 patient-days at risk for
      periods 2, 3, and 4, respectively. The mean (+/-SD) weekly rate of environmental
      sites cleaned increased from 0.48+/-0.08 at baseline to 0.87+/-0.08 in period 2;
      similarly high cleaning rates persisted in periods 3 and 4. Mean (+/-SD) weekly
      hand hygiene adherence rate was 0.40+/-0.01 at baseline and increased to 0.57+/
      0.11 in period 2, without a specific intervention to improve adherence, but
      decreased to 0.29+/-0.26 in period 3 and 0.43+/-0.1 in period 4. Mean proportions
      of positive results of cultures of environmental and hand samples decreased in
      period 2 and remained low thereafter. In a Cox proportional hazards model, the
      hazard ratio for acquiring VRE during periods 2-4 was 0.36 (95% confidence
      interval, 0.19-0.68); the only determinant explaining the difference in VRE
      acquisition was admission to the intensive care unit during period 1.
      CONCLUSIONS: Decreasing environmental contamination may help to control the
      spread of some antibiotic-resistant bacteria in hospitals.

PMID- 16652313
TI  - Nasopharyngeal shedding of severe acute respiratory syndrome-associated
      coronavirus is associated with genetic polymorphisms.
AB  - BACKGROUND: A high initial or peak severe acute respiratory syndrome (SARS)
      associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to
      be associated with a high mortality rate. Because all infected individuals were
      devoid of preeexisting protective immunity against SARS-CoV, the biological basis
      for the variable virus burdens in different patients remains elusive. METHODS:
      The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single
      nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with
      SARS, to identify SNPs for which distribution between patients with or without
      detectable nasopharyngeal shedding of SARS-CoV was biased. RESULTS: Titers of
      SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from
      nondetectable to 10(8) SARS-CoV RNA copies/mL, and they were correlated
      positively with a high mortality rate (P<.0001, by trend test) and with early
      death (i.e., death occurring within 2 weeks of the onset of illness) (P=.0015, by
      trend test). Virus shedding was found to be higher among male patients (P=.0014,
      by multivariate logistic regression) and among older patients (P=.015, by
      multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV
      was associated with polymorphic alleles of interleukins 18 (P=.014) and 1A
      (P=.031) and a member of NF kappa B complex (reticuloendotheliosis viral oncogene
      homolog B [RelB]) (P=.034), all of which are proinflammatory in nature, as well
      as the procoagulation molecule fibrinogen-like protein 2 (P=.008). CONCLUSION:
      The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is
      associated with polymorphisms of genes involved in innate immunity, which might
      be regulated in an age- and sex-dependent manner. The findings of the present
      study provided leads to genes involved in the host response to SARS-CoV
      infection; if substantiated with functional studies, these findings may be
      applicable to other newly emerged respiratory viruses (e.g., the influenza
      pandemic strain).

PMID- 16652315
TI  - Serotonin toxicity associated with the use of linezolid: a review of
      postmarketing data.
AB  - BACKGROUND: Linezolid is the first oxazolidinone antimicrobial marketed in the
      United States. It exhibits monoamine oxidase (MAO) type A and MAO type B
      inhibitory effects. The concomitant administration of nonselective MAO inhibitors
      or MAO-A inhibitors with drugs that increase serotonin concentrations is
      associated with serotonin toxicity. METHODS: We requested from the US Food and
      Drug Administration all postmarketing adverse event reports regarding linezolid
      that included serotonin toxicity or any report describing cognitive or behavioral
      symptoms and autonomic and neuromuscular excitability. We assessed the case
      summaries obtained from the Adverse Event Reporting System database for serotonin
      toxicity. A case of serotonin toxicity was defined as having the following: (1)
      linezolid as the primary suspect drug; (2) concurrent administration of > or =1
      secondary suspect drug known to increase serotonin concentrations in the central
      nervous system; and (3) serotonin toxicity, as defined by the modified Hunter
      Serotonin Toxicity Criteria or by the reporter. RESULTS: Twenty-nine cases were
      classified as serotonin toxicity. Patients' ages ranged from 17-83 years, and the
      ratio of females to males was 1:1. The most common class of drugs received
      concurrently with linezolid was selective serotonin reuptake inhibitors (26 of 43
      patients). Thirteen patients required an intervention to prevent permanent
      impairment or required hospitalization for the adverse event. CONCLUSION: The use
      of linezolid with medications that increase concentrations of serotonin in the
      central nervous system may result in serotonin toxicity. Prescribers must weigh
      risks and benefits of this combination. Patients and prescribers should be
      cognizant of signs and symptoms of serotonin toxicity and should initiate
      appropriate measures if such symptoms develop.

PMID- 16652314
TI  - Molecular and pharmacological determinants of the therapeutic response to
      artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria.
AB  - BACKGROUND: Our study examined the relative contributions of host,
      pharmacokinetic, and parasitological factors in determining the therapeutic
      response to artemether-lumefantrine (AL). METHODS: On the northwest border of
      Thailand, patients with uncomplicated Plasmodium falciparum malaria were enrolled
      in prospective studies of AL treatment (4- or 6-dose regimens) and followed up
      for 42 days. Plasma lumefantrine concentrations were measured by high performance
      liquid chromatography; malaria parasite pfmdr1 copy number was quantified using a
      real-time polymerase chain reaction assay (PCR), and in vitro drug susceptibility
      was tested. RESULTS: All treatments resulted in a rapid clinical response and
      were well tolerated. PCR-corrected failure rates at day 42 were 13% (95%
      confidence interval [CI], 9.6%-17%) for the 4-dose regimen and 3.2% (95% CI, 1.8%
      4.6%) for the 6-dose regimen. Increased pfmdr1 copy number was associated with a
      2-fold (95% CI, 1.8-2.4-fold) increase in lumefantrine inhibitory
      concentration(50) (P=.001) and an adjusted hazard ratio for risk of treatment
      failure following completion of a 4-dose regimen, but not a 6-dose regimen, of
      4.0 (95% CI, 1.4-11; P=.008). Patients who had lumefantrine levels below 175
      ng/mL on day 7 were more likely to experience recrudescence by day 42 (adjusted
      hazard ratio, 17; 95% CI, 5.5-53), allowing prediction of treatment failure with
      75% sensitivity and 84% specificity. The 6-dose regimen ensured that therapeutic
      levels were achieved in 91% of treated patients. CONCLUSIONS: The lumefantrine
      plasma concentration profile is the main determinant of efficacy of artemether
      lumefantrine. Amplification in pfmdr1 determines lumefantrine susceptibility and,
      therefore, treatment responses when plasma lumefantrine levels are
      subtherapeutic.

PMID- 16652316
TI  - Clinical issues regarding relapsing aspergillosis and the efficacy of secondary
      antifungal prophylaxis in patients with hematological malignancies.
AB  - Advancements in early diagnosis and the introduction of effective agents have
      improved the rates of response of aspergillosis to primary antifungal therapy.
      These changes allow the subsequent continuation of cytotoxic chemotherapy and/or
      performance of hematopoietic stem cell transplantation in an increasing number of
      patients with hematological malignancies. These developments have increased
      interest in secondary prophylaxis of aspergillosis, because the resumption of
      myelotoxic chemotherapy in these patients is associated with high rates of
      relapse of this opportunistic mycosis in the absence of prophylaxis. However, the
      risk factors for relapsing invasive aspergillosis and the strategies for reducing
      risk are not well defined. Furthermore, differentiating aspergillosis relapse
      from reinfection with a new Aspergillus isolate is problematic when using the
      available laboratory tools. We summarize the existing knowledge regarding the
      pathogenesis of, risk factors for, and natural history of relapsing invasive
      aspergillosis and review the limited data regarding the role of secondary
      antifungal prophylaxis.

PMID- 16652317
TI  - The risk of tuberculosis in patients with cancer.
AB  - Current US guidelines for the management of latent tuberculosis infection in
      cancer patients are based on studies from 1970s, yet much about cancer care has
      changed in the interim. In a review of our experience during the past 25 years,
      we found that incidence of tuberculosis varied significantly according to country
      of birth and cancer type. Foreign-born patients with underlying hematologic
      neoplasm had a tuberculosis rate 50-100 times higher than US-born patients,
      whereas US-born patients with an underlying solid tumor had the same tuberculosis
      rate as US-born persons without cancer. These findings may help guide the
      management of latent tuberculosis infection in persons with cancer.

PMID- 16652318
TI  - Fluoroquinolones and anaerobes.
AB  - The usefulness of fluoroquinolones for the treatment of mixed aerobic and
      anaerobic infections has been investigated since these agents started being used
      in clinical practice. Newer compounds have increased in vitro activity against
      anaerobes, but clinically relevant susceptibility breakpoints for these bacteria
      have not been established. Pharmacodynamic analyses and corroboration by new data
      from clinical trials have enhanced our knowledge concerning the use of
      fluoroquinolones to treat selective anaerobic pathogens. These studies suggest
      that newer agents could be useful in the treatment of several types of mixed
      aerobic and anaerobic infections, including skin and soft-tissue, intra
      abdominal, and respiratory infections. The major concerns with expanding the use
      of fluoroquinolones to treat anaerobic infections have been reports of increasing
      resistance in Bacteroides group isolates and the impact of these antibiotics on
      the incidence of Clostridium difficile-associated disease.

PMID- 16652319
TI  - Web resources for HIV type 1 genotypic-resistance test interpretation.
AB  - Interpreting the results of plasma human immunodeficiency virus type 1 (HIV-1)
      genotypic drug-resistance tests is one of the most difficult tasks facing
      clinicians caring for HIV-1-infected patients. There are many drug-resistance
      mutations, and they arise in complex patterns that cause varying levels of drug
      resistance. In addition, HIV-1 exists in vivo as a virus population containing
      many genomic variants. Genotypic-resistance testing detects the drug-resistance
      mutations present in the most common plasma virus variants but may not detect
      drug-resistance mutations present in minor virus variants. Therefore,
      interpretation systems are necessary to determine the phenotypic and clinical
      significance of drug-resistance mutations found in a patient's plasma virus
      population. We describe the scientific principles of HIV-1 genotypic-resistance
      test interpretation and the most commonly used Web-based resources for clinicians
      ordering genotypic drug-resistance tests.

PMID- 16652320
TI  - A randomized trial of directly administered antiretroviral therapy and adherence
      case management intervention.
AB  - BACKGROUND: A randomized, controlled trial was conducted to evaluate the impact
      of a directly administered antiretroviral therapy program (DAART) and intensive
      adherence case management (IACM) intervention on virologic and immunologic
      response to highly active antiretroviral therapy (HAART) among patients at 3
      public human immunodeficiency virus clinics in Los Angeles County, California.
      METHODS: Participants included 250 treatment-naive and treatment-experienced
      persons for whom no more than 1 prior HAART regimen had failed. Five days per
      week for 6 months, a community worker delivered 1 HAART dose to DAART
      participants and observed the participant take it. IACM participants met weekly
      with a case manager to overcome barriers to HAART adherence. A control group (the
      standard of care [SOC] group) received the usual care. RESULTS: The majority of
      patients were Latino (64%) or African American (24%); 57% were monolingual
      Spanish speakers. Seventy-five percent of the patients were male, and 64%
      reported an annual income of <10,000 dollars. In an intent-to-treat analysis, no
      statistical differences were observed in the percentage of patients with an
      undetectable viral load (i.e., <400 copies/mL) at 6 months between the DAART
      group (54%), IACM group (60%), and SOC group (54%; P>.05). An on-treatment
      analysis determined that there were no statistical differences in the percentage
      of patients with an undetectable viral load at 6 months between the DAART group
      (71%), IACM group (80%), and SOC group (74%; P>.05). Additionally, there were no
      statistical differences in 6-month changes in the CD4+ cell count or in self
      reported adherence to therapy. CONCLUSIONS: Among patients with limited prior
      HAART experience and adherence barriers that had not been assessed before
      randomization, no differences were found in virologic or immunologic response for
      DAART or IACM, compared with SOC, at 6 months. DAART and IACM did not improve
      short-term outcomes when SOC included other means of adherence support that were
      not controlled for by the study design.

PMID- 16652321
TI  - Directly administered antiretroviral therapy in methadone clinics is associated
      with improved HIV treatment outcomes, compared with outcomes among concurrent
      comparison groups.
AB  - BACKGROUND: Directly administered antiretroviral therapy (DAART) in methadone
      clinics has the potential to improve treatment outcomes for human
      immunodeficiency virus (HIV)-infected injection drug users (IDUs). METHODS: DAART
      was provided at 3 urban methadone clinics. Eighty-two participants who were
      initiating or reinitiating highly active antiretroviral therapy (HAART) received
      supervised doses of therapy at the clinic on the mornings on which they received
      methadone. Treatment outcomes in the DAART group were compared with outcomes in 3
      groups of concurrent comparison patients, who were drawn from the Johns Hopkins
      HIV Cohort. The concurrent comparison patients were taking HAART on a self
      administered basis. The 3 groups of concurrent comparison patients were as
      follows: patients with a history of IDU who were receiving methadone at the time
      HAART was used (the IDU-methadone group; 75 patients), patients with a history of
      IDU who were not receiving methadone at the time that HAART was used (the IDU
      nonmethadone group; 244 patients), and patients with no history of IDU (the non
      IDU group; 490 patients). RESULTS: At 12 months, 56% of DAART participants
      achieved an HIV type 1 RNA level <400 copies/mL, compared with 32% of
      participants in the IDU-methadone group (P=.009), 33% of those in the IDU
      nonmethadone group (P=.001), and 44% of those in the non-IDU group (P=.077). The
      DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3,
      compared with 21 cells/mm3 in the IDU-methadone group (P=.04), 33 cells/mm3 in
      the IDU-nonmethadone group (P=.09), and 84 cells/mm3 in the non-IDU group
      (P=.98). After adjustment for other covariates in a logistic regression model,
      DAART participants were significantly more likely to achieve viral suppression
      than were patients in each of the 3 comparison groups. CONCLUSIONS: These results
      suggest that methadone clinic-based DAART has the potential to provide
      substantial clinical benefit for HIV-infected IDUs.

PMID- 16652322
TI  - The good, the bad, and the ugly: providing highly active antiretroviral therapy
      when it is most difficult.

PMID- 16652323
TI  - Immune reconstitution syndrome in HIV: validating a case definition and
      identifying clinical predictors in persons initiating antiretroviral therapy.
AB  - BACKGROUND: Clinical deterioration after initiation of antiretroviral therapy may
      result from restored immunity. There is no standard clinical definition for
      immune reconstitution syndrome. The objectives of this study were to validate a
      proposed definition and to identify factors predictive of immune reconstitution
      syndrome. METHODS: This was a retrospective case-control study from an academic
      university medical practice. Cases were matched to > or =2 control subjects by
      CD4+ cell count at the time of initiation of antiretroviral therapy. Cases and
      "mock cases" were blindly reviewed by 2 human immunodeficiency virus (HIV)
      experts. RESULTS: Twenty possible cases of immune reconstitution syndrome were
      identified; HIV experts excluded all cases of herpes zoster (shingles), with
      agreement on real and mock cases of 92%. For 14 confirmed case patients (compared
      with 40 control subjects), immune reconstitution syndrome was associated with a
      higher number of prior opportunistic infections (P=.003) and higher CD8+ cell
      counts at baseline (P=.05) and at week 12 (P=.02). Immune reconstitution syndrome
      was associated with lower baseline levels of alanine aminotransferase (P=.05) and
      hemoglobin (P=.02). On multivariate analysis, the number of prior opportunistic
      infections (odds ratio, 2.7; P=.007) and lower hemoglobin level at baseline (odds
      ratio, 0.8; P=.003) were independently associated with development of immune
      reconstitution syndrome. A predictive model was defined by classification and
      regression tree analysis with a sensitivity and specificity of 78.57% and 87.50%,
      respectively, for an importance score of > or =4 (on a scale of 0.0 to 100.0),
      and 92.86% and 80.00%, respectively, for a score of > or =2, using the number of
      prior opportunistic infections, CD8+ cell count, and hemoglobin level.
      CONCLUSIONS: A standard definition for immune reconstitution syndrome is
      possible. Patients with a greater severity of illness at initiation of
      antiretroviral therapy are at risk for immune reconstitution syndrome. The model
      defined by classification and regression tree analysis may provide a basis for
      risk stratification before initiation of antiretroviral therapy.

PMID- 16652324
TI  - Oscar Costa-Mandry and posthurricane bacillary dysentery.
AB  - After the recent hurricanes Katrina and Rita, outbreaks of waterborne viral and
      bacterial diseases were expected. Dr. Oscar Costa-Mandry, a Puerto Rican
      bacteriologist and epidemiologist in the 1930s, identified the relationship
      between hurricanes and epidemic bacillary dysentery in townships that were
      directly affected by hurricanes.

PMID- 16652325
TI  - An association between reduced susceptibility to daptomycin and reduced
      susceptibility to vancomycin in Staphylococcus aureus.

PMID- 16652326
TI  - Acute schizophrenic symptoms as the initial manifestation of HIV infection that
      respond to highly active antiretroviral therapy.

PMID- 16652327
TI  - Vaccinia complications and methisazone therapy.

PMID- 16652328
TI  - Eosinophilia in refugees.

PMID- 16652329
TI  - Tenofovir-associated kidney diseases and interactions between tenofovir and other
      antiretrovirals.

PMID- 16652330
TI  - The role of drug interactions and monitoring in the prevention of tenofovir
      associated kidney disease.

PMID- 16652332
TI  - GENOMIZER: an integrated analysis system for genome-wide association data.
AB  - Genome-wide association analysis appears to be a promising way to identify
      heritable susceptibility factors for complex human disorders. However, the
      feasibility of large-scale genotyping experiments is currently limited by an
      incomplete marker coverage of the genome, a restricted understanding of the
      functional role of given genomic regions, and the small sample sizes used. Thus,
      genome-wide association analysis will be a screening tool to facilitate
      subsequent gene discovery rather than a means to completely resolve individual
      genetic risk profiles. The validation of association findings will continue to
      rely upon the replication of "leads" in independent samples from either the same
      or different populations. Even under such pragmatic conditions, the timely
      analysis of the large data sets in question poses serious technical challenges.
      We have therefore developed public-domain software, GENOMIZER, that implements
      the workflow of an association experiment, including data management, single
      point and haplotype analysis, "lead" definition, and data visualization.
      GENOMIZER (www.ikmb.uni-kiel.de/genomizer) comes with a complete user manual, and
      is open-source software licensed under the GNU Lesser General Public License. We
      suggest that the use of this software will facilitate the handling and
      interpretation of the currently emerging genome-wide association data.

PMID- 16652333
TI  - Reduced secretion of fibulin 5 in age-related macular degeneration and cutis
      laxa.
AB  - Age-related macular degeneration (ARMD) is the leading cause of irreversible
      visual loss in the Western world, affecting approximately 25 million people
      worldwide. The pathogenesis is complex and missense mutations in FBLN5 have been
      reported in association with ARMD. We have investigated the role of fibulin 5 in
      ARMD by completing the first European study of the gene FBLN5 in ARMD (using 2
      European cohorts of 805 ARMD patients and 279 controls) and by determining the
      functional effects of the missense mutations on fibulin 5 expression. We also
      correlated the FBLN5 genotype with the ARMD phenotype. We found two novel
      sequence changes in ARMD patients that were absent in controls and expressed
      these and the other nine reported FBLN5 mutations associated with ARMD and two
      associated with the autosomal recessive disease cutis laxa. Fibulin 5 secretion
      was significantly reduced (P<0.001) for four ARMD (p.G412E, p.G267S, p.I169 T,
      and p.Q124P) and two cutis laxa (p.S227P, p.C217R) mutations. These results
      suggest that some missense mutations associated with ARMD lead to decreased
      fibulin 5 secretion with a possible corresponding reduction in elastinogenesis.
      This study confirms the previous work identifying an association between FBLN5
      mutations and ARMD and for the first time suggests a functional mechanism by
      which these mutations can lead to ARMD. It further demonstrates that FBLN5
      mutations can be associated with different phenotypes of ARMD (not limited to the
      previously described cuticular drusen type). Such knowledge may ultimately lead
      to the development of novel therapies for this common disease.

PMID- 16652334
TI  - Megalencephalic leukoencephalopathy with subcortical cysts: an update and
      extended mutation analysis of MLC1.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal
      recessive cerebral white matter disorder in children. This disease is
      histopathologically characterized by myelin splitting and intramyelinic vacuole
      formation. MLC is caused by mutations in the gene MLC1, which encodes a novel
      protein, MLC1. Since the first report, 50 mutations in this gene have been found.
      Mutations occur throughout the entire coding region and include all different
      types: 11 splice-site mutations; one nonsense mutation; 24 missense mutations;
      and 14 deletions and insertions. Until now, six polymorphisms within the coding
      sequence of MLC1 had been reported. In about 20% of the patients with a typical
      clinical and MRI picture, no mutations in the MLC1 gene are found. Several of the
      families, in which no mutations are found, also do not show linkage with the MLC1
      locus, which suggests a second gene involved in MLC. The absence of mutations may
      also be the consequence of performing standard mutation analysis that can miss
      heterozygous deletions, mutations in the promoter, 3' and 5' untranslated regions
      (UTRs), and intron mutations, which may influence the amino acid composition of
      the end product. In this work we describe 13 novel mutations, including those
      found with extended mutation analysis on MLC patients. This study shows that
      extended mutation analysis is a valuable tool to identify at least some of the
      missing mutations. Therefore, we suggest extended mutation analysis for the MLC1
      gene, if no mutations are found during standard analysis.

PMID- 16652335
TI  - Pharmacological rescue of carnitine transport in primary carnitine deficiency.
AB  - Primary carnitine deficiency is a recessive disorder caused by heterogeneous
      mutations in the SLC22A5 gene encoding the OCTN2 carnitine transporter. Here we
      extend mutational analysis to eight new families with this disorder. To determine
      the mechanism by which missense mutations impaired carnitine transport, the OCTN2
      transporter was tagged with the green fluorescent protein and expressed in CHO
      cells. Analysis by confocal microscopy indicated that several missense mutants
      (M1I, R169W, T232 M, G242 V, S280F, R282Q, W283R, A301D, W351R, R399Q, T440 M,
      E452 K, and T468R) matured normally to the plasma membrane. By contrast, other
      mutations (including R19P, DeltaF22, R83L, S280F, P398L, Y447C, and A142S/R488 H)
      caused significant retention of the mutant OCTN2 transporter in the cytoplasm.
      Failed maturation to the plasma membrane is a common mechanism in disorders
      affecting membrane transporters/ion channels, including cystic fibrosis. To
      correct this defect, we tested whether drugs reducing the efficiency of protein
      degradation in the endoplasmic reticulum (ER) (phenylbutyrate, curcumin) or
      capable of binding the OCTN2 carnitine transporter (verapamil, quinidine) could
      improve carnitine transport. Prolonged incubation with phenylbutyrate, quinidine,
      and verapamil partially stimulated carnitine transport, while curcumin was
      ineffective. These results indicate that OCTN2 mutations can affect carnitine
      transport by impairing maturation of transporters to the plasma membrane.
      Pharmacological therapy can be effective in partially restoring activity of
      mutant transporters.

PMID- 16652336
TI  - A subset of patients with epithelial basement membrane corneal dystrophy have
      mutations in TGFBI/BIGH3.
AB  - Epithelial basement membrane corneal dystrophy (EBMD), also known as Cogan
      microcystic epithelial dystrophy or map-dot-fingerprint dystrophy, is a common
      bilateral epithelial dystrophy. Usually, this disease is not considered to be
      inherited although several families with autosomal dominant inheritance have been
      described. We report the analysis of two families with an autosomal dominant
      pattern of inheritance as well as the analysis of single affected individuals; we
      identified two different point mutations in the TGFBI/BIGH3 genes, genes known to
      be associated with other corneal dystrophies. This is the first report of a
      molecular mutation in individuals with EBMD and it increases the spectrum of
      mutations in the TGFBI/BIGH3 gene. Based on our screening, up to 10% of EBMD
      patients could have a mutation in this gene.

PMID- 16652337
TI  - Synergetic effects of quetiapine and venlafaxine in preventing the chronic
      restraint stress-induced decrease in cell proliferation and BDNF expression in
      rat hippocampus.
AB  - Clinical studies show better response rates of patients with depression and
      schizophrenia to combinations of atypical antipsychotics and antidepressants,
      compared to responses to either type of drugs alone. Animal studies demonstrate
      that some antipsychotics and antidepressants increase neurogenesis and BDNF
      expression in the hippocampus, which is reduced in volume in patients with
      depression or schizophrenia. We hypothesized that the better therapeutic effects
      of combined treatment seen in schizophrenia and depression patients are related
      to the additive or synergistic effects of combined treatment on hippocampal
      neurogenesis and BDNF expression. To test this hypothesis, we investigated the
      effects of chronic administration of quetiapine, venlafaxine, and their
      combination, on hippocampal cell proliferation and BDNF expression in rats, when
      subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week
      drug administration period. We found (1) CRS decreased hippocampal cell
      proliferation and BDNF expression; (2) chronic administration of quetiapine or
      venlafaxine dose-dependently prevented these decreases in hippocampal cell
      proliferation and BDNF expression caused by CRS (6 h/day for 14 days); (3) the
      combination of lower doses of quetiapine (5 mg/kg) and venlafaxine (2.5 mg/kg)
      increased hippocampal cell proliferation and prevented BDNF decrease in stressed
      rats, whereas each of the drugs exerted mild or no effects; (4) individual higher
      doses of quetiapine (10 mg/kg) or venlafaxine (5 mg/kg) exerted effects
      comparable to those produced by their combination. These results support our
      hypothesis and can lead to future studies to develop new therapeutic approaches
      for treatment-resistant depression and the negative symptoms of schizophrenia.

PMID- 16652338
TI  - Comparisons of PCR-based genome amplification systems using CpG island
      microarrays.
AB  - The characterization of complex DNA libraries by high-throughput sequencing
      technologies provides a powerful approach toward finding mutations and genetic
      variation in the human genome. However, the value of these analyses is highly
      dependent upon the quality of the DNA libraries themselves. For example, the
      sequence composition of libraries made using PCR-based procedures can be skewed
      due to biases in the amplification efficiency of individual library members.
      Here, we used CpG island microarrays to evaluate the biases incurred in PCR-based
      genome amplification using three different DNA polymerase mixtures designed to
      efficiently amplify problematic sequence tracts. Based on hybridization
      properties of dye-labeled DNA libraries to these microarrays, we quantified the
      overall and specific trends in the PCR efficiency of more than 1,400 sequences
      with high GC-content, which generally amplify with low efficiency using
      conventional PCR protocols. Overall, all three DNA polymerase mixtures produced
      libraries that show substantial increases in the representation of CpG island
      segments that poorly amplify with Taq DNA polymerase. However, the effects of
      these DNA polymerases were quite specific since they did not alter the relative
      representation of segments that efficiently amplify with Taq DNA polymerase.
      Furthermore, we demonstrate that DNA microarrays provide a robust platform for
      rapidly evaluating the ability of different PCR systems to amplify difficult
      genomic regions targeted for mutational, resequencing, and genotyping analyses.

PMID- 16652339
TI  - MRI analysis of in vivo meniscal and tibiofemoral kinematics in ACL-deficient and
      normal knees.
AB  - The objectives of this study were to analyze simultaneously meniscal and
      tibiofemoral kinematics in healthy volunteers and anterior cruciate ligament
      (ACL)-deficient patients under axial load-bearing conditions using magnetic
      resonance imaging (MRI). Ten healthy volunteers and eight ACL-deficient patients
      were examined with a high-field, closed MRI system. For each group, both knees
      were imaged at full extension and partial flexion ( approximately 45 degrees )
      with a 125N compressive load applied to the foot. Anteroposterior and
      medial/lateral femoral and meniscal translations were analyzed following three
      dimensional, landmark-matching registration. Interobserver and intraobserver
      reproducibilities were less than 0.8 mm for femoral translation for image
      processing and data analysis. The position of the femur relative to the tibia in
      the ACL-deficient knee was 2.6 mm posterior to that of the contralateral, normal
      knee at extension. During flexion from 0 degrees to 45 degrees , the femur in ACL
      deficient knees translated 4.3 mm anteriorly, whereas no significant translation
      occurred in uninjured knees. The contact area centroid on the tibia in ACL
      deficient knees at extension was posterior to that of uninjured knees.
      Consequently, significantly less posterior translation of the contact centroid
      occurred in the medial tibial condyle in ACL-deficient knees during flexion.
      Meniscal translation, however, was nearly the same in both groups. Axial load
      bearing MRI is a noninvasive and reproducible method for evaluating tibiofemoral
      and meniscal kinematics. The results demonstrated that ACL deficiency led to
      significant changes in bone kinematics, but negligible changes in the movement of
      the menisci. These results help explain the increased risk of meniscal tears and
      osteoarthritis in chronic ACL deficient knees.

PMID- 16652340
TI  - Inducible gene deletion in astroglia and radial glia--a valuable tool for
      functional and lineage analysis.
AB  - Astrocytes are thought to play a variety of key roles in the adult brain, such as
      their participation in synaptic transmission, in wound healing upon brain injury,
      and adult neurogenesis. However, to elucidate these functions in vivo has been
      difficult because of the lack of astrocyte-specific gene targeting. Here we show
      that the inducible form of Cre (CreERT2) expressed in the locus of the astrocyte
      specific glutamate transporter (GLAST) allows precisely timed gene deletion in
      adult astrocytes as well as radial glial cells at earlier developmental stages.
      Moreover, postnatal and adult neurogenesis can be targeted at different stages
      with high efficiency as it originates from astroglial cells. Taken together, this
      mouse line will allow dissecting the molecular pathways regulating the diverse
      functions of astrocytes as precursors, support cells, repair cells, and cells
      involved in neuronal information processing.

PMID- 16652341
TI  - Olig gene function in CNS development and disease.
AB  - Olig1 and Olig2 encode basic helix-loop-helix (bHLH) transcription factors that
      are expressed in both the developing and mature vertebrate central nervous
      system. While numerous studies have established critical functions for Olig genes
      during the formation of motor neurons and oligodendrocytes of the ventral neural
      tube, their roles at later stages of development and in adulthood have remained
      relatively obscure. Recent studies, however, reveal that in the fetal dorsal
      spinal cord and neural progenitor cells of the adult brain, Olig expression
      continues to mark, and may regulate, the formation of oligodendroglia. Studies of
      Olig expression in human brain tumors and repair of demyelinating lesions suggest
      the possibility of additional functions in a variety of neurological diseases.

PMID- 16652342
TI  - Minced cartilage without cell culture serves as an effective intraoperative cell
      source for cartilage repair.
AB  - Traumatic articular cartilage injuries heal poorly and may predispose patients to
      the early onset of osteoarthritis. One current treatment relies on surgical
      delivery of autologous chondrocytes that are prepared, prior to implantation,
      through ex vivo cell expansion of cartilage biopsy cells. The requirement for
      cell expansion, however, is both complex and expensive and has proven to be a
      major hurdle in achieving a widespread adoption of the treatment. This study
      presents evidence that autologous chondrocyte implantation can be delivered
      without requiring ex vivo cell expansion. The proposed improvement relies on
      mechanical fragmentation of cartilage tissue sufficient to mobilize embedded
      chondrocytes via increased tissue surface area. Our outgrowth study, which was
      used to demonstrate chondrocyte migration and growth, indicated that fragmented
      cartilage tissue is a rich source for chondrocyte redistribution. The
      chondrocytes outgrown into 3-D scaffolds also formed cartilage-like tissue when
      implanted in SCID mice. Direct treatment of full-thickness chondral defects in
      goats using cartilage fragments on a resorbable scaffold produced hyaline-like
      repair tissue at 6 months. Thus, delivery of chondrocytes in the form of
      cartilage tissue fragments in conjunction with appropriate polymeric scaffolds
      provides a novel intraoperative approach for cell-based cartilage repair.

PMID- 16652343
TI  - Microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3
      pathway and modulate the cell activation toward a neuroprotective role.
AB  - Microglia perform both neuroprotective and neurotoxic functions in the brain,
      with this depending on their state of activation and their release of mediators.
      Upon P2X(7) receptor stimulation, for example, microglia release small amounts of
      TNF, which protect neurons, whereas LPS causes massive TNF release leading to
      neuroinflammation. Here we report that, in rat primary cultured microglia,
      nicotine enhances P2X(7) receptor-mediated TNF release, whilst suppressing LPS
      induced TNF release but without affecting TNF mRNA expression via activation of
      alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs). In microglia, nicotine
      elicited a transient increase in intracellular Ca(2+) levels, which was abolished
      by specific blockers of alpha7 nAChRs. However, this response was independent of
      extracellular Ca(2+) and blocked by U73122, an inhibitor of phospholipase C
      (PLC), and xestospongin C, a blocker of the IP(3) receptor. Repeated experiments
      showed that currents were not detected in nicotine-stimulated microglia.
      Moreover, nicotine modulation of LPS-induced TNF release was also blocked by
      xestospongin C. Upon LPS stimulation, inhibition of TNF release by nicotine was
      associated with the suppression of JNK and p38 MAP kinase activation, which
      regulate the post-transcriptional steps of TNF synthesis. In contrast, nicotine
      did not alter any MAP kinase activation, but enhanced Ca(2+) response in P2X(7)
      receptor-activated microglia. In conclusion, microglial alpha7 nAChRs might drive
      a signaling process involving the activation of PLC and Ca(2+) release from
      intracellular Ca(2+) stores, rather than function as conventional ion channels.
      This novel alpha7 nAChR signal may be involved in the nicotine modification of
      microglia activation towards a neuroprotective role by suppressing the
      inflammatory state and strengthening the protective function.

PMID- 16652344
TI  - Response to rituximab in a child with neuroblastoma and opsoclonus-myoclonus.
AB  - Opsoclonus-myoclonus (OM) is a paraneoplastic syndrome of probable autoimmune
      origin. Despite current therapies aimed at decreasing autoantibody formation, OM
      is difficult to control and may impact long-term neurologic outcome. We present a
      case of a 19-month-old patient who initially presented with OM, neuroblastoma and
      a constitutional cytogenetic abnormality t(5;12)(q11.2;q15). The patient's OM was
      recalcitrant to conventional therapies, but showed significant improvement
      following treatment with rituximab.

PMID- 16652345
TI  - Neuroblastomas that might benefit from mass screening at 6 months of age in
      Japan.

PMID- 16652346
TI  - Maxillary ameloblastic carcinoma in a child.
AB  - We report an extremely rare occurrence of ameloblastic carcinoma located in the
      maxilla of a pediatric patient. Wide surgical resection was done along with
      adjuvant radiotherapy because of involved surgical margins. Histopathological
      diagnosis was established with morphological features of both ameloblastoma and
      carcinoma.

PMID- 16652347
TI  - The cathepsin D rs17571 polymorphism: effects on CSF tau concentrations in
      Alzheimer disease.
AB  - The lysosomal protease cathepsin D (CtsD, EC 3.4.23.5; gene, CTSD) has been
      associated with Alzheimer disease (AD) due to its cerebral expression being
      increased early in the course of AD; additionally, a CTSD exon 2 polymorphism
      (rs17571; NT_009237.17:g.569834T>C) may confer risk to AD. Functionally, it may
      be implicated in amyloid precursor protein (APP) processing and tau protein
      degradation. The objective of this study was to determine whether the CTSD exon 2
      polymorphism affects cerebrospinal fluid (CSF), concentrations of beta-amyloid
      (Abeta42) and tau in two independent samples from Germany (n=73) and Sweden
      (n=66). Patients carrying the CTSD rs17571-T allele had significantly decreased
      CSF levels of tau (Munich, p=0.003; Swedish, p=0.029; combined sample, p<0.001),
      whereas no significant effect was observed on Abeta42 concentrations. Likewise,
      no significant impact was observed on Mini Mental State Examination (MMSE)
      scores. The data of both independent samples suggest that the CTSD rs17571
      polymorphism does not affect APP processing but shows significant effects on tau
      processing. The result may corroborate the implication of the lysosomal system in
      the pathogenesis of AD and is of particular importance if CSF tau is used as a
      diagnostic biomarker.

PMID- 16652349
TI  - Hypertension and prehypertension in long-term survivors of childhood and
      adolescent cancer.
AB  - BACKGROUND: Hypertension as a late effect following childhood and adolescent
      cancer has received little attention. Since obesity, a known risk factor for
      hypertension, is increased following some childhood cancers, it seems likely that
      significant numbers of survivors would have hypertension. PROCEDURES: The records
      of patients seen in the Long Term Follow Up Clinic of Children's National Medical
      Center were examined for a single institution, retrospective study of blood
      pressure in survivors of childhood and adolescent cancer. Of 103 consecutive
      survivors who attended the clinic from January 1 through June 30, 2004, 51
      (49.5%) were female and 52 (50.5%) were male. Their mean age was 14.6 years.
      Systolic and diastolic blood pressures for children and adolescents under 18
      years of age were evaluated for hypertension and prehypertensive according to
      standards for age, sex, and height. Blood pressures for adults 18 years of age
      and older were evaluated according to standard adult values. Children and
      adolescents were evaluated for obesity and overweight according to body mass
      index (BMI) standards for age and sex. Adults were evaluated according to
      standard adult values. RESULTS: Twenty-nine patients (28.2%) were hypertensive or
      prehypertensive, and 74 (71.8%) were normal. Thirty-eight patients (36.9%) were
      obese or overweight, and 65 (63.1%) were non-obese. Most Wilms tumor patients, 7
      of 10 (70.0%), had hypertension or prehypertension, but only 4 of 10 (40.0%) were
      obese or overweight. CONCLUSION: Careful follow-up of their blood pressure status
      is warranted for long-term survivors of childhood and adolescent cancer,
      especially for those with an initial diagnosis of Wilms tumor.

PMID- 16652348
TI  - The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer.
AB  - Homozygous mutation in the ATM gene causes ataxia telangiectasia and heterozygous
      mutation carriers may be at increased risk of breast cancer. We studied a total
      of 22 ATM variants; 18 variants were analyzed in one of two large population
      based studies from the U.S. and Poland, and four variants were analyzed in all
      2,856 breast cancer cases and 3,344 controls from the two studies. The missense
      mutation Ser49Cys (c.146C>G, p.S49C), carried by approximately 2% of subjects,
      was more common in cases than controls in both study populations, combined odds
      ratio (OR) 1.69 (95% CI, 1.19-2.40; P=0.004). Another missense mutation at
      approximately 2% frequency, Phe858Leu (c.2572T>C, p.F858L), was associated with a
      significant increased risk in the U.S. study but not in Poland, and had a
      combined OR of 1.44 (95% CI, 0.98-2.11; P=0.06). These analyses provide the most
      convincing evidence thus far that missense mutations in ATM, particularly p.S49C,
      may be breast cancer susceptibility alleles. Because of their low frequency, even
      larger sample sizes are required to more firmly establish these associations.

PMID- 16652350
TI  - Incidence and survival of childhood Langerhans cell histiocytosis in Northwest
      England from 1954 to 1998.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder
      of pathological Langerhans cells, for which the aetiology and pathogenesis remain
      largely unknown. PROCEDURE: Information on the 101 children with LCH registered
      with the population-based Manchester Children's Tumour Registry (MCTR) between
      1954 and 1998 was extracted from the records of the MCTR. This included age, sex,
      date of diagnosis, systems affected at diagnosis and follow-up. RESULTS: The
      overall incidence rate for LCH was 2.6 cases per million child years. In those
      under 1 year of age the incidence rate was 9.0 cases per million child years,
      compared to 0.7 cases per million in those aged 10-14 years (P < 0.0001 for age
      trend). There was no evidence of seasonal variation in presentation by month of
      birth or first symptom. Bone was the most common site of disease involvement (67%
      of cases), followed by skin (37%) and soft tissue (22%). The overall survival
      rate has improved over time, from 57% in 1954-1968 to 74% in 1985-1998. Ninety
      percent of deaths were due to disease progression, the remainder were due to
      complications of intensive therapy. The site of LCH lesions and extent of disease
      present at diagnosis strongly predicted survival outcome. Patients with initial
      liver involvement had a 5-year survival rate of 25% compared with 93% for those
      with bone lesions alone at diagnosis. CONCLUSIONS: Incidence rates varied
      significantly by age at diagnosis, and have been stable over time. Survival has
      improved considerably over time, but varies strongly by age and systems affected
      at diagnosis.

PMID- 16652351
TI  - Congenital dysgranulopoietic neutropenia.
AB  - We investigated a 15-year-old female with congenital dysgranulopoietic
      neutropenia (CDN) and her non-neutropenic mother who had recurrent stomatitis. In
      both patients, cells of the neutrophilic, eosinophilic, monocytic,
      megakaryocytic, and basophilic series were dysmorphic. Plasmacytoid lymphocytes
      and mild megaloblastic erythroid precursors were present. Bleeding times of both
      patients were prolonged. The mother had a secondary aggregation defect; the
      number of the plasmacytoid lymphocytes, dense granules of platelets, and
      dysmorphic neutrophils, neutrophil chemotaxis, and myeloperoxidase content
      fluctuated according to the presence or not of aphthae. The daughter's karyotype
      revealed 46,XX/46,XX, t(1;8). No ELA2 or G-CSFR mutation was detected. These
      findings support stem cell involvement in CDN.

PMID- 16652352
TI  - Solution scattering studies of conformation stability of xylanase XYNII from
      Trichoderma longibrachiatum.
AB  - Xylanase (endo-1,4-beta-xylanase; EC 3.2.1.8) is an enzyme that catalyzes the
      hydrolysis reaction of xylan. The structure of the xylanase II (XYNII) molecule
      from Trichoderma longibrachoatum (formerly Trichoderma reesei) in a solution and
      at different pH values has been studied by small- and wide-angle scattering of
      synchrotron radiation (SAXS-WAXS). Analysis of the radius of gyration that
      characterizes xylanase has confirmed the stability of the above enzyme structure
      (the radius of gyration varied from 1.65 to 1.74 nm). On the basis of the SAXS
      data, the low-resolution structure of the xylanase molecule in solution has been
      reconstructed by using ab initio methods and programs DALAI_GA and DAMMIN. The
      full SAXS-WAXS data set (0.15 > s > 9.5 nm(-1)) fed to the program GASBOR
      permitted us to construct a chain-like spatial distribution of a dummy residues
      model of the xylanase molecule. The shape of the model molecules is similar to
      that of xylanase molecule in the crystal and shows the characteristic asymmetry
      that makes the molecule to resemble a right hand.

PMID- 16652353
TI  - Number of pericryptal fibroblasts correlates with density of distinct mast cell
      phenotypes in the crypt lamina propria of human duodenum: implications for the
      homeostasis of villous architecture.
AB  - Pericryptal fibroblasts (PFs), a class of myofibroblasts, have strongly been
      implicated in the regulation of villous structure because of their location close
      to crypts and their ability to secrete cytokines affecting intestinal epithelial
      cell proliferation and differentiation. Recently, mast cells (MCs) have also been
      involved in the homeostasis of villous architecture. As myofibroblasts arise in a
      wide variety of settings concurrently with a local increase in the number of
      tissue MCs, we calculated in this study the density of both PF and distinct
      pericryptal MC phenotypes in the mucosa of human duodenum showing normal,
      defective, or atrophic villous profiles. In addition, we evaluated the
      statistical association between PF-MC densities and each pattern of villous
      architecture. Finally, we correlated the density of PF with the density of
      pericryptal MC phenotypes. For this purpose, samples taken by endoscopy from 30
      patients complaining of inflammatory bowel disorders were studied by
      immunohistochemistry. The densities of alpha-smooth muscle actin-positive PFs as
      well as tryptase-, chymase-, and c-kit-positive MCs were determined in the crypt
      lamina propria. Villous architecture was found to be significantly associated
      with the number of PFs and tryptase-, chymase-, c-kit-positive MCs in the lamina
      propria (ANOVA group effect P < 0.001). High density of both PFs and MCs was
      found in intestinal samples with normal villous morphology while lower densities
      were associated with defective or atrophic villous profiles (Tukey's test for
      multiple comparison P < 0.001). In addition, a significant correlation was found
      between PF density and the density of each pericryptal MC phenotype (vs. tryptase
      positive MCs, r = 0.913; vs. chymase-positive MC, r = 0.905; vs. c-kit-positive
      MC, r = 0.927; P < 0.001 in all cases). This study provides morphological support
      for an important cooperation between PFs and MCs in maintaining normal villous
      architecture.

PMID- 16652354
TI  - p53 and its downstream proteins as molecular targets of cancer.
AB  - The p53 tumor suppressor gene plays a key role in prevention of tumor formation
      through transcriptional dependent and independent mechanisms. Transcriptional
      dependent mechanisms are mainly mediated by p53 regulation of downstream targets,
      leading to growth arrest and apoptosis. Mutational inactivation of the p53 gene
      is detected in more than 50% of human cancers. Mutation of p53 renders cancer
      cells more resistant to current cancer therapies due to lack of p53-mediated
      apoptosis. Extensive studies have been conducted to identify small molecules that
      manipulate p53, including restoration of mutant p53 conformation to wild-type,
      disruption of murine double minute-2 (Mdm2)-p53 binding to increase p53 level and
      inhibition of Mdm2 E3 ubiquitin ligase activity to prevent p53 degradation.
      Another approach was to identify and validate "drugable" target(s) in p53
      signaling pathways that modulate p53-induced apoptosis. We profiled a p53
      temperature-sensitive lung cancer cell model with the Affymetrix human HG-U133
      GeneChip, covering the entire human transcriptome. We identified thousands of
      unique genes that were either induced or repressed in response to p53-induced
      apoptosis. A follow-up study characterized a p53-repressed gene, SAK, a polo-like
      kinase (PLK) family member, as an appealing cancer drug target. Snk/Plk-akin
      kinase (SAK) silencing via small interfering RNA (siRNA) induced apoptosis,
      whereas SAK overexpression attenuated p53-induced apoptosis. Thus, SAK repression
      by p53 contributes to p53-induced apoptosis. Future work is directed at
      determining the normal cell response to SAK silencing. If a therapeutic window is
      obtained, a SAK inhibitor identified from high throughput screening (HTS) could
      serve as a lead compound for development of a novel class of apoptosis-inducing
      anticancer drugs.

PMID- 16652355
TI  - Molecular targets for the cancer preventive activity of tea polyphenols.
AB  - Inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated in
      many animal models. The mechanisms of action have been extensively investigated
      mostly in cell culture systems with (-)-epigallocatechin-3-gallate (EGCG), the
      most active and major polyphenolic compound from green tea. However, the
      mechanisms of cancer preventive activity by tea and tea polyphenols are not
      clearly understood. This article discusses some of the reported mechanisms and
      possible targets for the action of EGCG. The difficulties and major issues in
      extrapolating data from studies in cancer cell lines to cancer prevention
      mechanisms are discussed. Activities observed in cell culture with high
      concentrations of EGCG may not be relevant because of the limited systemic
      bioavailability of EGCG. In addition, possible artifacts due to the auto
      oxidation of EGCG may complicate this issue. Some recent studies revealed high
      affinity EGCG binding proteins as possible direct targets for the action of EGCG.
      Validating the related cancer preventive mechanisms found in in vitro studies in
      animal models and human samples would be exciting.

PMID- 16652356
TI  - Results of a SNP genome screen in a large Costa Rican pedigree segregating for
      severe bipolar disorder.
AB  - We have ascertained in the Central Valley of Costa Rica a new kindred (CR201)
      segregating for severe bipolar disorder (BP-I). The family was identified by
      tracing genealogical connections among eight persons initially independently
      ascertained for a genome wide association study of BP-I. For the genome screen in
      CR201, we trimmed the family down to 168 persons (82 of whom are genotyped),
      containing 25 individuals with a best-estimate diagnosis of BP-I. A total of
      4,690 SNP markers were genotyped. Analysis of the data was hampered by the size
      and complexity of the pedigree, which prohibited using exact multipoint methods
      on the entire kindred. Two-point parametric linkage analysis, using a
      conservative model of transmission, produced a maximum LOD score of 2.78 on
      chromosome 6, and a total of 39 loci with LOD scores >1.0. Multipoint parametric
      and non-parametric linkage analysis was performed separately on four sections of
      CR201, and interesting (nominal P-value from either analysis <0.01), although not
      statistically significant, regions were highlighted on chromosomes 1, 2, 3, 12,
      16, 19, and 22, in at least one section of the pedigree, or when considering all
      sections together. The difficulties of analyzing genome wide SNP data for complex
      disorders in large, potentially informative, kindreds are discussed.

PMID- 16652357
TI  - De novo pure 12q22q24.33 duplication: first report of a case with mental
      retardation, ADHD, and Dandy-Walker malformation.
AB  - We present a patient with a de novo 12q nonmosaic pure duplication characterized
      by multiple minor anomalies and Dandy-Walker malformation. A neurological and
      behavioral assessment revealed psychomotor retardation and attention
      deficit/hyperactivity disorder (ADHD), with neurobehavioral abnormalities (auto-
      and heteroaggressive behavior). Fluoxetine therapy in this case markedly improved
      the neurobehavioral profile, with a decreased level of aggression. To define the
      extension of the duplicated region, we performed FISH analyses by using YAC
      probes. The analyses revealed a tandem duplication of the 12q22q24.33 region,
      with the proximal breakpoint located between 96.5 and 97.6 cM and the distal one
      between 154 and 161 cM. This is the first case of pure de novo duplication
      involving the 12q22q24.33 region. To better define the clinical phenotype
      associated with 12q partial duplication, we compared our case with the four
      patients with similar pure duplications previously described.

PMID- 16652358
TI  - Intrachromosomal triplication 12p11.22-p12.3 and gonadal mosaicism of partial
      tetrasomy 12p.
AB  - Cases of tetrasomy 12p and trisomy 12p are known to be associated with specific
      phenotypic abnormalities well described in the literature. Here, we report on the
      unusual case of a partial tetrasomy 12p found in an affected patient and in a
      mosaic constellation in the patient's mother, who showed no phenotypic
      abnormality. The index patient was a 16-year-old boy with clinical features
      similar to the "trisomy 12p syndrome" including mental retardation, macrocephaly,
      a short nose with anteverted nostrils, and a broad protruding lower lip. G
      banding analysis and fluorescence in situ hybridization (FISH) experiments using
      locus specific YAC DNA probes revealed a derivative chromosome 12 with a partial
      triplication of the short arm with an inverted copy, flanked by two direct
      copies. Chromosome analyses in parental lymphocytes showed a chromosomal
      mosaicism in the phenotypically normal mother, with 12% cells exhibiting the same
      partial tetrasomy 12p as detected in her son. The allelic pattern of short tandem
      repeats (STR) in the mother's blood DNA showed that a chimerism can be excluded
      with high probability. To our knowledge, this is the first report of
      intrachromosomal triplication on chromosome 12, as well as partial tetrasomy 12p
      mosaicism. Moreover, as a consequence of the chromosomal aberration in the son it
      can be concluded that a gonadal mosaicism is present in the mother.

PMID- 16652359
TI  - Response to "Letter: Fibular aplasia, tibial campomelia and oligosyndactyly" by
      Evans and Elliott.

PMID- 16652360
TI  - Pregnancy outcome of fetuses with trisomy 18 identified by prenatal sonography
      and chromosomal analysis in a perinatal center.
AB  - To investigate the pregnancy outcome of fetuses affected with trisomy 18, we
      analyzed 63 cases diagnosed at our hospital from January 1993 to December 2004.
      Twenty-nine were males and 34 were females. Fifty-eight were prenatally
      diagnosed, and in 16 (27.6%) of them intrauterine fetal death (IUFD) occurred
      between 28 weeks and 41 weeks gestation (34.6 +/- 3.9 weeks, Mean +/- SD). Ten
      (17.2%) fetuses died during labor and their age ranged from 30 weeks to 40 weeks
      of gestation. The total number of cases ending in fetal demise was 26 (44.8%) and
      the mean gestational age at the time of fetal demise was 35.0 +/- 3.6 weeks (Mean
      +/- SD). All liveborn infants (n = 36) were born after 31 weeks gestation. In our
      study the preterm birth ratio for trisomy 18 is 34.8%, which is much higher than
      the ratio for the general population. Females are more likely than males to be
      long-term survivors. These data are helpful in the counseling of parents faced
      with the difficult decision of whether or not to continue a pregnancy with a
      fetus affected with trisomy 18.

PMID- 16652361
TI  - A population-based case-control study of isolated primary congenital glaucoma.
AB  - We studied the possible etiological factors of isolated primary congenital
      glaucoma (IPCG) using data from the Hungarian Case-Control Surveillance of
      Congenital Abnormalities, 1980-2002. The study group consisted of 52 cases with
      IPCG compared to 52 matched control pairs without any defects, and 22,744
      malformed controls with non-ocular defects and 37,837 population controls with no
      defect. Exposure data and family history were collected (i) prospectively by
      prenatal logbook and other medical records, (ii) retrospectively through a
      structured questionnaire completed by mothers, and (iii) from supplementary
      information obtained by regional nurses visiting the homes of non-respondent
      mothers. Autosomal recessive inheritance of IPCG was suspected on the basis of
      sib occurrence and parental consanguinity in 15% of cases. The shorter
      gestational age (with high proportion of preterm birth), higher birth order,
      large proportion of births among unmarried women, low socioeconomic status, and
      high rate of unemployment may be related to Gypsy origin of at least 54% of cases
      of IPCG. We conclude that the higher incidence of IPCG in the Hungarian Gypsy
      population is associated with their inbreeding and the possible founder effect of
      a gene mutation.

PMID- 16652362
TI  - When is a "positive" association truly a "positive" in psychiatric genetics? A
      commentary based on issues debated at the World Congress of Psychiatric Genetics,
      Boston, October 12-18, 2005.
AB  - The accumulated literature on candidate gene findings in psychiatric genetics is
      extensive. There is concern that many of the published findings to data are false
      positives. At the October 2005 World Congress of Psychiatric Genetics this issue
      was discussed by a panel of experts. This manuscript describes the panel
      discussion, its implications for the reporting of association studies of
      psychiatric disorders and suggestions for when to decide that a positive finding
      is truly positive.

PMID- 16652363
TI  - Transgenic mice expressing tamoxifen-inducible Cre for somatic gene modification
      in renal epithelial cells.
AB  - Gene inactivation often leads to an embryonic-lethal phenotype. In focal diseases
      like renal cell carcinomas and polycystic kidney disease, somatic gene
      inactivation in subsets of cells is likely to occur at later stages. We generated
      a transgenic mouse line with an inducible form of Cre recombinase for conditional
      gene modifications in kidney epithelial cells. To this end a 1.4-kb promoter
      fragment of the kidney-specific cadherin gene (KspCad) was cloned upstream of a
      tamoxifen-inducible Cre recombinase (CreER(T2)) encoding sequence. Expression and
      activity of Cre was evaluated using reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis and by crossbreeding to Z/EG reporter mice. One KspCad
      CreER(T2) line showed kidney-specific Cre expression and mediated recombination
      upon tamoxifen treatment in Z/EG reporter mice. No reporter gene expression was
      detected in untreated animals or in extrarenal tissues upon treatment. Within the
      kidneys, enhanced green fluorescent protein (EGFP) fluorescence was observed in
      epithelial cells in several nephronic segments. In addition, the system
      successfully recombined a floxed Pkd1 gene.

PMID- 16652364
TI  - Temporal regulation of Cre recombinase activity in neural stem cells.
AB  - Neural stem cells are known to give rise to distinct subtypes of neurons and
      glial cells over time by changing their competency. However, precise
      characterization of neural stem cells at various developmental stages remains to
      be performed. For such analysis, a tool to manipulate neural stem cells at
      different time points is necessary. Here, we generated transgenic mice that
      express Cre-ER(T2) in the ventricular zone of the developing nervous system under
      the control of the nestin promoter and enhancer (Nes-CreER(T2)). In mice
      expressing Cre-ER(T2) at appropriate levels, Cre recombinase activity was mostly
      inactive but efficiently activated by tamoxifen within 1 day. When such mice were
      crossed with the ROSA-26 or Z/EG reporter mice, neural stem cells were
      permanently labeled after administration of tamoxifen. Thus, Nes-CreER(T2) mice
      offer a powerful tool to manipulate neural stem cells genetically at desired time
      points.

PMID- 16652365
TI  - Cortical, callosal, and thalamic connections from primary somatosensory cortex in
      the naked mole-rat (Heterocephalus glaber), with special emphasis on the
      connectivity of the incisor representation.
AB  - We investigated the distribution of cortical, callosal, and thalamic connections
      from the primary somatosensory area (S1) in naked mole-rats, concentrating on
      lower incisor and forelimb representations. A neuronal tracer (WGA-HRP) was
      injected into the center of each respective representation under guidance from
      microelectrode recordings of neuronal activity. The locations of cells and
      terminals were determined by aligning plots of labeled cells with flattened
      cortical sections reacted for cytochrome oxidase. The S1 lower incisor area was
      found to have locally confined intrahemispheric connections and longer
      connections to a small cluster of cells in the presumptive secondary
      somatosensory (S2) and parietal ventral (PV) incisor fields. The S1 incisor area
      also had sparse connections with anterior cortex, in presumptive primary motor
      cortex. Homotopic callosal projections were identified between the S1 lower
      incisor areas in each hemisphere. Thalamocortical connections related to the
      incisor were confined to ventromedial portions of the ventral posterior medial
      subnucleus (VPM) and posterior medial nucleus (Po). Injections into the S1
      forelimb area revealed reciprocal intrahemispheric connections to S2 and PV, to
      two areas in frontal cortex, and to two areas posterior to S1 that appear
      homologous to posterior lateral area and posterior medial area in rats. The S1
      forelimb representation also had callosal projections to the contralateral S1
      limb area and to contralateral S2 and PV. Thalamic distribution of label from
      forelimb injections included ventral portions of the ventral posterior lateral
      subnucleus (VPL), dorsolateral Po, the ventral lateral nucleus, and the ventral
      medial nucleus and neighboring intralaminar nuclei.

PMID- 16652366
TI  - Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc
      deficiency during pregnancy.
AB  - Subfamily II of the solute-linked carrier 39A superfamily contains three well
      conserved zinc transporters (ZIPs1, 2, 3) whose physiological functions are
      unknown. We generated mice homozygous for knockout alleles of ZIP1 and both ZIP1
      and ZIP 3 (double-knockout). These mice were apparently normal when dietary zinc
      was replete, but when dietary zinc was limited during pregnancy embryos from ZIP1
      or ZIP3 knockout mice were two to three times more likely to develop abnormally
      than those in wildtype mice, and 91% (71/78) of embryos developed abnormally in
      ZIP1, ZIP3 double-knockout mice. Analysis of the patterns of expression of these
      genes in mice revealed predominate expression in intestinal stromal cells,
      nephric-tubular epithelial cells, pancreatic ductal epithelial cells, and
      hepatocytes surrounding the central vein. This suggests that these zinc
      transporters function, at least in part, in the redistribution and/or retention
      of zinc rather than its acquisition from the diet. In conclusion, mutations in
      the ZIP1 and ZIP3 zinc transporter genes are silent when dietary intake of zinc
      is normal, but can dramatically compromise the success of pregnancy when dietary
      intake of zinc is limiting.

PMID- 16652367
TI  - Generation of mice harboring a Sox6 conditional null allele.
AB  - Sox6 belongs to the family of Sry-related HMG box transcription factors, which
      determine cell fate and differentiation in various lineages. Sox6 is expressed in
      several tissues, including cartilage, testis, neuronal, and erythropoietic
      tissues. Mice lacking Sox6 have revealed critical roles for Sox6 in several of
      these tissues, but their multiple defects and early lethality has limited studies
      in specific cell types and in postnatal mice. We show here that we have generated
      mice harboring a Sox6 conditional null allele (Sox6(fl+)) by flanking the second
      coding exon with loxP sites. This allele encodes wildtype Sox6 protein, is
      expressed normally, and is efficiently converted into a null allele (Sox6(fl-))
      by Cre-mediated recombination in somatic and germ cells. Sox6(fl+/fl+) mice are
      indistinguishable from wildtype mice, and Sox6(fl-/fl-) mice from Sox6(-/-) mice.
      These Sox6 conditional null mice will thus be valuable for further uncovering the
      roles of Sox6 in various processes in vivo.

PMID- 16652368
TI  - Successful thrombus extraction with the Rescue thrombus management system during
      acute percutaneous coronary intervention improves flow but does not necessarily
      restore optimal myocardial tissue perfusion.
AB  - We determined the effectiveness of the Rescue device in restoring flow and
      achieving optimal tissue perfusion during percutaneous coronary intervention
      (PCI) in thrombus-laden coronary arteries. METHODS: A total of 30 patients with
      an acute coronary syndrome underwent PCI using the Rescue device. RESULTS: The
      mean age was 65.5 +/- 9.8 years. Although the Rescue device could not be passed
      across the lesion in 6 (20%) cases, debris was aspirated in 26 (87%). The
      uncorrected TIMI frame count improved following the use of the Rescue device and
      improved further at the completion of PCI (92.2 +/- 23.9 pre-PCI vs. 38.7 +/-
      31.3 post-Rescue vs. 21.96 +/- 24 post-PCI, P < 0.0001). The thrombus score
      improved from 4 +/- 0 to 2.2 +/- 1.29 to 0.86 +/- 1.4 (P < 0.0001). TIMI flow
      grade (TFG) 3 was restored in 60% of cases following the Rescue device and in 87%
      after PCI. Myocardial blush grade 3 occurred in only 13% of patients following
      the Rescue device and 37% of patients after PCI. CONCLUSION: These data suggest
      that the Rescue device can aspirate considerable amounts of debris in the
      majority of patients and significantly improves the angiographic epicardial
      coronary blood flow. How effective such a device is in improving tissue perfusion
      and, thereby, clinical outcomes for patients remains to be seen.

PMID- 16652369
TI  - Model averaging in linkage analysis.
AB  - Methods for genetic linkage analysis are traditionally divided into "model
      dependent" and "model-independent," but there may be a useful place for an
      intermediate class, in which a broad range of possible models is considered as a
      parametric family. It is possible to average over model space with an empirical
      Bayes prior that weights models according to their goodness of fit to
      epidemiologic data, such as the frequency of the disease in the population and in
      first-degree relatives (and correlations with other traits in the pleiotropic
      case). For averaging over high-dimensional spaces, Markov chain Monte Carlo
      (MCMC) has great appeal, but it has a near-fatal flaw: it is not possible, in
      most cases, to provide rigorous sufficient conditions to permit the user safely
      to conclude that the chain has converged. A way of overcoming the convergence
      problem, if not of solving it, rests on a simple application of the principle of
      detailed balance. If the starting point of the chain has the equilibrium
      distribution, so will every subsequent point. The first point is chosen according
      to the target distribution by rejection sampling, and subsequent points by an
      MCMC process that has the target distribution as its equilibrium distribution.
      Model averaging with an empirical Bayes prior requires rapid estimation of
      likelihoods at many points in parameter space. Symbolic polynomials are
      constructed before the random walk over parameter space begins, to make the
      actual likelihood computations at each step of the random walk very fast. Power
      analysis in an illustrative case is described. (c) 2006 Wiley-Liss, Inc.

PMID- 16652370
TI  - Anti-angiogenic drugs: from bench to clinical trials.
AB  - Angiogenesis, the generation of new capillaries through a process of pre-existing
      microvessel sprouting, is under stringent control and normally occurs only during
      embryonic and post-embryonic development, reproductive cycle, and wound repair.
      However, in many pathological conditions (solid tumor progression, metastasis,
      diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among
      others), the disease appears to be associated with persistent upregulated
      angiogenesis. The development of specific anti-angiogenic agents arises as an
      attractive therapeutic approach for the treatment of cancer and other
      angiogenesis-dependent diseases. The formation of new blood vessels is a complex
      multi-step process. Endothelial cells resting in the parent vessels are activated
      by an angiogenic signal and stimulated to synthesize and release degradative
      enzymes allowing endothelial cells to migrate, proliferate and finally
      differentiate to give rise to capillary tubules. Any of these steps may be a
      potential target for pharmacological intervention. In spite of the disappointing
      results obtained initially in clinical trials with anti-angiogenic drugs, recent
      reports with positive results in phases II and III trials encourage expectations
      in their therapeutic potential. This review discusses the current approaches for
      the discovery of new compounds that inhibit angiogenesis, with emphasis on the
      clinical developmental status of anti-angiogenic drugs.

PMID- 16652371
TI  - Augmented cancer resistance and DNA damage response phenotypes in PPM1D null
      mice.
AB  - The p53-induced serine/threonine phosphatase, protein phosphatase 1D magnesium
      dependent, delta isoform (PPM1D) (or wild-type p53-induced phosphatase 1 (Wip1)),
      exhibits oncogenic activity in vitro and in vivo. It behaves as an oncogene in
      rodent fibroblast transformation assays and is amplified and overexpressed in
      several human tumor types. It may contribute to oncogenesis through functional
      inactivation of p53. Here, we show that the oncogenic function of PPM1D is
      associated with its phosphatase activity. While overexpressed PPM1D may be
      oncogenic, PPM1D null mice are resistant to spontaneous tumors over their entire
      lifespan. This cancer resistance may be based in part on an augmented stress
      response following DNA damage. PPM1D null mice treated with ionizing radiation
      display increased p53 protein levels and increased phosphorylation of p38 MAP
      kinase, p53, checkpoint kinase 1 (Chk1), and checkpoint kinase 2 (Chk2) in their
      tissues compared to their wild-type (WT) counterparts. Male PPM1D null mice show
      a modest reduction in longevity, reduced serum insulin-like growth factor 1 (IGF
      1) levels, and reduced body weight compared to WT mice. The PPM1D null mouse
      phenotypes indicate that PPM1D has a homeostatic role in abrogating the DNA
      damage response and may regulate aspects of male longevity.

PMID- 16652372
TI  - Roles of reactive oxygen species in hepatocarcinogenesis and drug resistance gene
      expression in liver cancers.
AB  - Hepatocellular carcinoma (HCC) has traditionally been an attractive system for
      cancer research because many animal HCC models are available. It is well known
      that liver tumors in animals can be induced by many different protocols, such as
      chronic hepatitis viral infections, carcinogens, toxins, steroid hormones, and
      dietary intervention. Although these different inducers have different cellular
      targets and modes of cytotoxic effects, their common denominator is the formation
      of reactive oxygen species (ROS). In this review, we present compelling evidence
      to support the hypothesis that ROS play important roles in hepatocarcinogenesis
      and the associated upregulation of drug resistance gene expression.

PMID- 16652373
TI  - DNA repair gene polymorphisms and probability of p53 mutation in bladder cancer.
AB  - We investigated if the presence of single nucleotide polymorphisms (SNPs) in the
      XRCC1, XRCC3, and XPD genes were associated with the type and frequency of p53
      mutations in bladder cancer. Using a hospital-based case-control study we have
      previously reported risks for the XRCC1 codon 194, XRCC1 codon 399, XRCC3 codon
      241, and XPD codon 751 SNPs 1-3. We have also previously reported mutation data
      for 149 cases from this study who were screened for mutations in exons 4 through
      9 of the p53 gene 4. Here we investigate possible associations between the DNA
      repair SNPs mentioned above and the presence of p53 mutations by comparing the
      frequency of each genotype between p53 mutation positive and negative cases. We
      also considered different classes of p53 mutations, including any mutation
      (nonsense, missense or silent), transversions and transitions and estimated odds
      ratios (ORs) and 95% confidence intervals (CI) for these associations. Cases with
      the XRCC1 codon 399 Gln/Gln genotype were positively associated with the presence
      of p53 transversions (OR = 4.8; 94% CI = 0.8-30). Cases with the XPD codon 751
      Gln/Gln genotype were positively associated with the presence of p53 transitions
      (OR = 2.8; 95% CI = 0.8-9.3), in particular G:C-A:T transitions (OR = 3.7; 95% CI
      = 1.1-13). Our data provide some limited support for the hypothesis that
      mutations in the p53 gene in bladder cancer may differ according to the presence
      or absence of certain DNA repair gene variants.

PMID- 16652374
TI  - c-jun/AP-1 activation does not affect the antiproliferative activity of phenethyl
      isothiocyanate, a cruciferous vegetable-derived cancer chemopreventive agent.
AB  - Cruciferous vegetable-derived isothiocyanates (ITCs) display potent cancer
      chemopreventive activity, but also markedly stimulate oncogenic activator protein
      1 (AP-1). AP-1 is well known to promote cell survival and proliferation. We
      examined the impact of AP-1 activation on antiproliferative activity of ITCs,
      using bladder cancer cells and phenethyl isothiocyanate (PEITC) as models. AP-1
      transactivation induced by PEITC was almost completely suppressed by a dominant
      negative c-jun (TAM67). However, suppression of AP-1 transactivation did not
      affect PEITC-induced apoptosis or cell-cycle arrest. Moreover, we previously
      showed that in response to ITC treatment c-jun was predominantly stimulated among
      AP-1 family members largely by c-jun N-terminal kinase (JNK) [Food Chem Toxicol
      2005; 43: 1373-1380], but neither JNK inhibition nor forced expression of c-jun
      altered the antiproliferative activity of PEITC. In addition, cyclin D1, which is
      considered as an AP-1 target gene and promotes cell proliferation, was markedly
      elevated in PEITC-treated cells. Unexpectedly, neither TAM67 or JNK inhibition,
      nor forced c-jun expression had a significant impact on cyclin D1 induction by
      PEITC, indicating that c-jun/AP-1 does not play an important role in cyclin D1
      induction by PEITC. In conclusion, despite the known role of c-jun/AP-1 as a
      stimulator of cell growth and proliferation, our data show that its activation
      does not diminish the antiproliferative activity of PEITC and is not responsible
      for cyclin D1 induction by PEITC.

PMID- 16652375
TI  - Strain-specific induction of murine lung tumors following in utero exposure to 3
      methylcholanthrene.
AB  - Fetal mice are more sensitive to chemical carcinogens than are adults. We
      previously demonstrated that resistant offspring of a DBA/2 x (C57BL/6 x DBA2)
      backcross exhibited a high incidence of lung tumors 12-13 mo after transplacental
      exposure to 3-methylcholanthrene (MC). We compared the effects of in utero
      treatment with MC on lung tumor incidence in the offspring of intermediately
      susceptible BALB/c (C), resistant C57BL/6 (B6), and reciprocal crosses between
      these strains. Pregnant mice were treated with 45 mg/kg of MC on day 17 of
      gestation and tumor incidence, multiplicity, and the Ki-ras mutational spectrum
      determined in the offspring 12-18 mo after birth. Tumor incidences in C mice and
      reciprocal crosses were 86% and 100%, respectively, while B6 mice demonstrated
      resistance to tumorigenesis, with a tumor incidence of 11%. Tumor multiplicities
      in C, B6C, CB6, and B6 mice were 3.3 +/- 3.2, 5.8 +/- 3.2, 5.0 +/- 2.7, and <0.1,
      respectively. Ki-ras mutations, which occurred chiefly in the K(s) allele (96%),
      were found in 79-81% of reciprocally crossed F1 mice, 64% of C mice, and 50% of
      B6 mice, with the Val(12), Asp(12), and Arg(13) mutations associated with more
      aggressive tumors. A subset of these mice was used to demonstrate the utility of
      computer tomography (CT) for the visualization and measurement of lung tumors in
      the submillimeter range in vivo. Based on known genetic differences in murine
      strains for lung cancer, our results suggest the presence of a previously
      unidentified genetic factor(s) which appears to specifically influence lung
      tumorigenesis following exposure to carcinogens during fetal development.

PMID- 16652376
TI  - Antitumor activity of an Ets protein, PEA3, in breast cancer cell lines MDA-MB
      361DYT2 and BT474M1.
AB  - Polyomavirus enhancer activator 3 (PEA3) is a member of the Ets family of
      transcription factors. We demonstrated in a previous study that, by
      downregulating the HER-2/neu oncogene at the transcriptional level, PEA3 can
      inhibit the growth and development into tumors of HER-2/neu-overexpressing
      ovarian cancer cells. Here, we establish stable clones of the human breast cancer
      cell line MDA-MB-361DYT2 that express PEA3 under the control of a tetracycline
      inducible promoter. Ectopic expression of PEA3 in this cell line inhibited cell
      growth and resulted in cell cycle accumulation in the G1 phase. We demonstrate
      that expression of PEA3 in an orthotopic breast cancer model inhibited tumor
      growth and prolonged the survival of tumor-bearing mice. In a parallel experiment
      with another breast cancer cell line, BT474M1, we were unable to obtain stable
      PEA3-inducible transfectants, suggesting that PEA3 may exert a strong growth
      inhibition effect in this cell line. Indeed, PEA3 coupled with the liposome SN2
      demonstrated therapeutic effects in mice bearing tumors induced by BT474M1. These
      results provide evidence for the antitumor activity of PEA3 in human breast
      cancers.

PMID- 16652377
TI  - Dietary agents as histone deacetylase inhibitors.
AB  - In cancer cells, an imbalance often exists between histone acetyltransferase
      (HAT) and histone deacetylase (HDAC) activities, and various drug companies are
      actively seeking competitive HDAC inhibitors for chemotherapeutic intervention.
      Cancer cells appear to be more sensitive than nontransformed cells to HDAC
      inhibitors, which disrupt the cell cycle and induce apoptosis via derepression of
      genes such as P21 and BAX. However, in the search for potent HDAC inhibitors with
      cancer therapeutic potential, a tendency exists to overlook or dismiss weak
      ligands that could prove effective in cancer prevention. Butyrate, diallyl
      disulfide (DADS), and sulforaphane (SFN) are three dietary agents that exhibit
      HDAC inhibitory activity in vitro and/or in vivo, and other such dietary agents
      probably will be discovered that affect HDAC activity. We make the distinction
      between 'pharmacologic' agents that potently derepress gene expression, during
      therapeutic intervention, and dietary HDAC inhibitors that, as weak ligands,
      might subtly regulate the expression of genes involved in cell growth and
      apoptosis. An important issue for future study is to determine the extent to
      which dietary HDAC inhibitors, by modulating genes such as p21 and Bax, enable
      normal, nontransformed cells to respond most effectively to external stimuli and
      toxic insults.

PMID- 16652378
TI  - Targeting carcinogenesis: a role for the prolyl isomerase Pin1?
AB  - Phosphorylation of proteins on serine or threonine residues that immediately
      precede proline (pSer/Thr-Pro) is a central signaling mechanism in cell
      proliferation and transformation. Recent studies indicate that certain pSer/Thr
      Pro motifs in native proteins exist in two completely distinct conformations, cis
      and trans, whose conversion is markedly slowed down upon phosphorylation, but
      specifically catalyzed by the peptidyl-prolyl cis/trans isomerase Pin1.
      Importantly, such Pin1-catalyzed conformational changes can have profound effects
      on the function of many phosphorylation signaling pathways, thereby playing an
      important role in various cellular processes. Moreover, increasing evidence
      indicates that aberrant Pin1 function plays an important role in the pathogenesis
      of some human diseases. Notably, Pin1 is not only overexpressed in a large number
      of human cancers, but also is an excellent prognostic marker in some cancers.
      Furthermore, Pin1 overexpression can function as a critical catalyst that
      amplifies multiple oncogenic signaling pathways during oncogenesis. Moreover,
      Pin1 overexpression causes cell transformation, centrosome amplification, genomic
      instability, and tumor development. In contrast, Pin1 knockout in mice prevents
      certain oncogenes from inducing tumors and Pin1 inhibition in cancer cells
      suppresses their cell proliferation, transformed phenotype and tumorigenicity in
      nude mice as well as increases the response to other anticancer agents. These
      results suggest that Pin1-mediated postphosphorylation regulation may provide a
      unique opportunity for disrupting oncogenic pathways, and thereby represent an
      appealing target for novel anticancer therapies.

PMID- 16652379
TI  - Construct validity of the incontinence severity index.
AB  - AIMS: To assess the construct validity of the incontinence severity index (ISI)
      by testing its correlation with two health-related quality of life measures, the
      short forms of the Urogenital Distress Inventory (UDI-6) and the Incontinence
      Impact Questionnaire (IIQ-7), in women with urodynamic stress incontinence.
      MATERIALS AND METHODS: A cohort of 170 women with the urodynamic stress
      incontinence who underwent corrective surgery completed the ISI, IIQ-7, and the
      UDI-6 both pre- and post-treatment. We correlated the pre- and post-treatment
      responses between the ISI, the IIQ-7, the UDI-6 and their subscales. We also
      assessed the sensitivity of the ISI to change by correlating the percent change
      in score between the three instruments. The results were analyzed using a non
      parametric test of correlation, the Spearman's rho. RESULTS: The ISI scores were
      generally not well correlated with the pre-treatment IIQ-7 and UDI-6 scores (r <
      0.40). The post-treatment scores and percent change from pre- to post-treatment
      of the ISI, however, were highly correlated with that of the IIQ-7 and UDI-6 (r's
      > 0.70, P < 0.001). The ISI was most highly correlated with the UDI-6 stress
      symptoms subscale and most poorly correlated with the UDI-6
      obstructive/discomfort subscale. CONCLUSIONS: This study provides valuable
      insight into the construct validity of the ISI. Evidence of its convergent
      validity is found in the high correlation with the stress symptoms subscales of
      the UDI-6, while the poorer correlation with the obstructive subscale provides
      evidence of its divergent validity. These data also suggest that the ISI is
      highly sensitive to change seen with treatment.

PMID- 16652380
TI  - Global ratings of patient satisfaction and perceptions of improvement with
      treatment for urinary incontinence: validation of three global patient ratings.
AB  - AIMS: To test the validity of three patient global ratings, satisfaction,
      perception of improvement, and estimated percent improvement, for measuring
      outcomes of behavioral treatment for urinary incontinence. METHODS: This report
      is a secondary analysis of data from three randomized controlled trials testing
      behavioral interventions for incontinence. Participants were 359 community
      dwelling women, aged 40-92 years, with stress, urge, or mixed urinary
      incontinence. All participants received an 8-week program of clinic-based or self
      administered behavioral training. Subjective outcomes included a patient
      satisfaction question (PSQ), global perception of improvement (GPI), and
      estimated percent improvement (EPI). Convergent validity was tested by examining
      the relationship between each measure and reduction of incontinence (bladder
      diary), change on the incontinence impact questionnaire (IIQ), and desire for
      another treatment. Discriminant validity was explored by examining the
      relationship of the global ratings to five measures not expected to be related to
      outcome (age, race, BMI, education level, and change in perceived pain). RESULTS:
      All three patient global ratings were significantly associated with each other (P
      < 0.0001), with diary measures of reduction of incontinence episodes (P <
      0.0001), and change in the IIQ (P < 0.005), and inversely associated with desire
      for another treatment (P < 0.0001). All three patient ratings were not
      significantly associated with age, race, BMI, education level, or change in
      perceived pain. CONCLUSION: Patient global ratings of satisfaction, perception of
      improvement, and estimated percent improvement have acceptable convergent and
      discriminant validity for measuring outcomes in studies of behavioral treatment
      for urinary incontinence.

PMID- 16652381
TI  - Ultrasound measurement of detrusor wall thickness in healthy adults.
AB  - AIMS: Measurements of detrusor wall thickness (DWT) are used to diagnose bladder
      outlet obstruction (BOO). No values of DWT exist in healthy adults so far. These
      values, however, are necessary to judge DWT in patients with suspected BOO
      correctly. The aim of this study was to determine DWT in healthy adults and to
      investigate if bladder filling, gender, age, or body-mass index (BMI) influences
      DWT. MATERIALS AND METHODS: In 55 healthy adult volunteers between 15 and 40
      years of age, DWT was measured at the anterior bladder wall with a 7.5 MHz
      ultrasound probe and with a full bladder. In nine of those volunteers, an
      urodynamic investigation was performed additionally during which DWT was measured
      in steps of 50 ml until 300 ml and in steps of 100 ml until the maximum bladder
      volume. RESULTS: DWT decreases rapidly during the first 250 ml of bladder filling
      but, thereafter, remains almost stable until maximal bladder capacity. No
      statistical difference was found between DWT at 250 ml and DWT at a higher
      bladder filling. Men had a greater DWT compared to women (1.4 vs. 1.2 mm, P <
      0.001). The age and BMI did not have a significant impact on DWT. CONCLUSIONS:
      DWT remains stable at a bladder filling of 250 ml. At this state of bladder
      filling, DWT between different groups are comparable. Men have to be evaluated
      separately from women.

PMID- 16652382
TI  - Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation
      of prostate cancer.
AB  - BACKGROUND: Prostate cancer (PC) contains a minor component of neuroendocrine
      (NE) cells that may stimulate androgen-independent growth of the tumor. The
      mechanism of neuroendocrine differentiation remains unknown. METHODS: The
      expression of PTP1B, a protein tyrosine phosphatase, was studied in LNCaP cells
      induced to show neuroendocrine phenotype by androgen withdrawal. Wild-type PTP1B
      and its dominant-negative mutant were transfected into LNCaP cells to study their
      effects on neuroendocrine differentiation. In vivo expression of PTP1B in human
      prostate cancer was studied by immunohistochemistry. RESULTS: Androgen withdrawal
      of LNCaP cells led to increased expression of PTP1B with a corresponding increase
      in its tyrosine phosphatase activity. Overexpression of PTP1B in LNCaP cells led
      to neuroendocrine differentiation while expression of its dominant-negative
      mutant inhibited neuroendocrine differentiation. Immunohistochemical study showed
      that PTP1B was exclusively expressed in neuroendocrine cells of human prostate
      cancer tissue. CONCLUSION: Our findings suggest that PTP1B plays an important
      role in neuroendocrine differentiation, and therefore, may possibly be involved
      in the progression of prostate cancer.

PMID- 16652383
TI  - Genistein-induced neuroendocrine differentiation of prostate cancer cells.
AB  - BACKGROUND: Neuroendocrine (NE) cells are present in normal prostate and their
      number appears to be increased in advanced prostate cancer (PCA). In this study,
      we studied the effect of the phytoestrogen, genistein, on NE differentiation of
      LNCaP cells in vitro. METHODS: Neuroendocrine marker expression of LNCaP cells
      exposed to genistein was measured by immunohistochemistry, Western blot, and real
      time PCR methods. Western blot analysis was used to study cell cycle and
      signaling pathways induced by genistein treatment. RESULTS: Six days after
      continuous genistein treatment, the majority of genistein-surviving cancer cells
      underwent transdifferentiation into a NE-like phenotype overexpressing the NE
      markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE
      differentiation process was associated with upregulation of the cell cycle
      modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways.
      CONCLUSION: Our data indicate that genistein evokes not only apoptosis but also
      NE transdifferentiation of PCA cells.

PMID- 16652384
TI  - Overexpression of EIF3S3 promotes cancer cell growth.
AB  - BACKGROUND: Amplification and overexpression of EIF3S3 gene has been demonstrated
      in breast and prostate cancer. Here, our goal was to study the effect of EIF3S3
      on cell growth. METHODS: The effect of EIF3S3 on growth of NIH 3T3 murine
      fibroblasts as well as breast (SK-Br-3 and ZR-75-1) and prostate (PC-3 and LNCaP)
      cancer cell lines was examined by using transfection with inducible pTet-Off
      system and siRNAs. RESULTS: NIH 3T3 cells with overexpression of EIF3S3 grew
      significantly faster than cells transfected with empty vector and survived longer
      when grown in soft agar. The EIF3S3 overexpression was associated with increased
      fraction of cells in S-phase and with phosphorylation of retinoblastoma (Rb)
      protein. siRNA treatment inhibited significantly (P = 0.0022) the growth of all
      breast and prostate cancer cell lines studied. CONCLUSIONS: The results suggest
      that EIF3S3 regulates cell growth and viability, and that overexpression of the
      gene may provide growth advantage to the cancer cells.

PMID- 16652385
TI  - A histone deacetylation-dependent mechanism for transcriptional repression of the
      gap junction gene cx43 in prostate cancer cells.
AB  - BACKGROUND: The connexin 43 gene (cx43, GJA1) mediates gap junctional
      intercellular communication (GJIC), which regulates tissue homeostasis. cx43 is
      frequently downregulated in prostate cancer. We investigated the role of a
      histone deacetylase (HDAC)-dependent mechanism in the transcriptional repression
      of cx43 in a panel of prostate cancer cells. METHODS: The impact of Trichostatin
      A (TSA), an inhibitor of HDAC, on exogenous and endogenous cx43 gene
      transcription was examined by the luciferase assay, Northern blot, nuclear run
      on, Western blot, and chromatin immunoprecipitation assays. RESULTS: Trichostatin
      A induces transcription of cx43 gene and GJIC. The co-activator p300/CBP
      synergizes with TSA for cx43 promoter activation. We identified a promoter region
      where cooperation between Ap1 and Sp1 elements was essential for TSA-induced cx43
      transcription. TSA increased the level of hyperacetylated histones bound to cx43
      promoter. CONCLUSION: Our results highlight the potential utility of inhibitors
      of HDAC to restore cx43 gene expression in prostate cancer.

PMID- 16652386
TI  - Androgen and anti-androgen treatment modulates androgen receptor activity and DJ
      1 stability.
AB  - BACKGROUND: Mechanisms regulating the transition from hormone responsive to
      hormone refractory prostate cancer (PCa) have remained unclear. METHODS: We
      analyzed androgen and anti-androgen treatment on endogenous AR activity in
      primary human prostate epithelial (HPE) cells cultured directly from patient
      radical prostatectomy specimens utilizing a transiently infected gene reporter
      (TIGR) assay. RESULTS: Flutamide treatment exhibited agonist activities in HPE
      cells derived from tumor and non-tumor specimens which contained wild-type AR.
      After proteomic comparison of these cells to those where flutamide functioned
      normally as an antagonist, we identified DJ-1, a positive regulator of AR. DJ-1
      expression increased in HPE and LNCaP cells during flutamide treatment as a
      result of DJ-1 protein stabilization. CONCLUSION: Stabilization of AR and its co
      regulators in the absence of androgen may partially account for anti-androgen
      withdrawal syndrome and potentially contribute to the development of hormone
      refractory PCa.

PMID- 16652387
TI  - Finasteride targets prostate vascularity by inducing apoptosis and inhibiting
      cell adhesion of benign and malignant prostate cells.
AB  - BACKGROUND: This study investigated the effects of finasteride, a 5alpha
      reductase inhibitor, clinically used for the treatment of benign prostatic
      hyperplasia (BPH) on prostate tumor vascularity, apoptosis, and cell adhesion in
      situ and in vitro. METHODS: Prostate specimens from BPH patients treated with
      finasteride for 1-12 months (n = 13), or without finasteride treatment (n = 14),
      were evaluated for apoptosis (TUNEL assay), microvessel density (Factor VIII),
      and prostate specific antigen (PSA) immunoreactivity. In vitro, the effect of
      finasteride was investigated in benign prostate cells, BPH-1, and its tumorigenic
      derivatives, CAFTD-01 and CAFTD-03, using Hoechst staining and cell adhesion
      assays. RESULTS: A significant increase in the apoptotic index, and reduced
      microvessel density and PSA expression were detected in prostates from
      finasteride-treated patients, compared to controls (P < 0.01). In vitro
      finasteride led to a significant decrease in prostate epithelial cell adhesion (P
      < 0.05). CONCLUSIONS: Finasteride can induce prostate apoptosis and reduce tissue
      vascularity by inhibiting epithelial cell adhesion. This evidence supports that
      finasteride has apoptotic and anti-angiogenic effects against benign and
      malignant prostate.

PMID- 16652388
TI  - Expression of mTOR signaling pathway markers in prostate cancer progression.
AB  - BACKGROUND: The PI3K/AKT/mTOR pathway is central to prostate cancer progression.
      A preliminary investigation of immuno-histochemical expression of mammalian
      target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of
      expression in prostate tissue. METHODS: Immunohistochemistry was performed on a
      custom-made prostate tissue array. Mean long scores and variability of long
      scores for each marker were recorded for normal lumenal cells, prostate
      intraepithelial neoplasia (PIN), and cancer. RESULTS: Expression of PTEN
      decreased and mTOR signaling pathway markers increased in PIN and in cancer as
      compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and
      p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression
      of 4E-BP1 was significantly higher than with any other marker. DISCUSSION:
      Results suggest that 4E-BP1 overexpression is strongly associated with prostate
      cancer, especially when combined with PTEN and mTOR expression data. Hierarchical
      clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer
      cell populations in most cases.

PMID- 16652389
TI  - The economics of diagnosis.
AB  - Any population can be divided into two groups, one with the presence of a given
      disease or condition, and the other without. Diagnosis consists of using tests to
      sort the population into these groups. Diagnostic tests use a threshold value of
      a diagnostic variable to distinguish between disease-positive and disease
      negative individuals. The analysis of error in diagnostic tests has typically
      been undertaken using receiver-operator characteristic (ROC) curves. More
      recently, economic value of information (VOI) methods have characterised the
      costs and consequences of testing. This paper develops a new method for economic
      test evaluation, which we call ROTS analysis. The ROTS curve plots the costs and
      effects of changing test thresholds, in cost-effectiveness space. We illustrate
      the use of our method with a worked example, and show how it can answer three key
      questions: (1) Is there any test that is worth doing? (2) What is a test's
      optimum operating point in terms of sensitivity and specificity? (3) If two tests
      are available, which is best? We contrast the merits of our method with those of
      established ROC and VOI analysis. We argue that ROTS analysis more clearly
      reveals the link between changing test thresholds and the cost-effectiveness of
      different treatments.

PMID- 16652390
TI  - Microarray detection of novel nuclear RNA substrates for the exosome.
AB  - Microarray analyses were performed on yeast strains mutant for the nuclear
      specific exosome components Rrp6p and Rrp47p/Lrp1p or the core component
      Rrp41p/Ski6p, at permissive temperature and following transfer to 37 degrees C.
      339 mRNAs showed clearly altered expression levels, with an unexpectedly high
      degree of heterogeneity in the different exosome mutants. In contrast, no clear
      alterations were seen in strains lacking the cytoplasmic exosome component Ski7p.
      27 mRNAs that were overexpressed in each strain defective in the nuclear exosome
      are good candidates for regulation by nuclear turnover. These included the mRNA
      for the autoregulated RNA-binding protein Nrd1p. Northern and primer extension
      analyses confirmed the elevated NRD1 mRNA levels in exosome mutants, and revealed
      the accumulation of truncated 5' fragments of the mRNA. These contain a predicted
      Nrd1p-binding site, potentially sequestering the protein and disrupting its
      autoregulation. Several genes located immediately downstream of independently
      transcribed snoRNA genes were overexpressed in exosome mutants, presumably due to
      stabilization of the products of transcription termination read-through. Further
      analyses indicated that many snoRNA and snRNA genes are inefficiently terminated,
      but read-through transcripts into downstream ORFs are normally rapidly degraded
      by the exosome.

PMID- 16652391
TI  - A 5-hydroxymethyl furfural reducing enzyme encoded by the Saccharomyces
      cerevisiae ADH6 gene conveys HMF tolerance.
AB  - The fermentation of lignocellulose hydrolysates by Saccharomyces cerevisiae for
      fuel ethanol production is inhibited by 5-hydroxymethyl furfural (HMF), a furan
      derivative which is formed during the hydrolysis of lignocellulosic materials.
      The inhibition can be avoided if the yeast strain used in the fermentation has
      the ability to reduce HMF to 5-hydroxymethylfurfuryl alcohol. To enable the
      identification of enzyme(s) responsible for HMF conversion in S. cerevisiae,
      microarray analyses of two strains with different abilities to convert HMF were
      performed. Based on the expression data, a subset of 15 reductase genes was
      chosen to be further examined using an overexpression strain collection. Three
      candidate genes were cloned from two different strains, TMB3000 and the
      laboratory strain CEN.PK 113-5D, and overexpressed using a strong promoter in the
      strain CEN.PK 113-5D. Strains overexpressing ADH6 had increased HMF conversion
      activity in cell-free crude extracts with both NADPH and NADH as co-factors. In
      vitro activities were recorded of 8 mU/mg with NADH as co-factor and as high as
      1200 mU/mg for the NADPH-coupled reduction. Yeast strains overexpressing ADH6
      also had a substantially higher in vivo conversion rate of HMF in both aerobic
      and anaerobic cultures, showing that the overexpression indeed conveyed the
      desired increased reduction capacity.

PMID- 16652392
TI  - Mass spectrometry-based profiling of phospholipids and sphingolipids in extracts
      from Saccharomyces cerevisiae.
AB  - Lipids are rapidly moving to centre stage in many fields of biological sciences.
      Lipidomics, the systems-level scale analysis of lipids and their interacting
      factors, is thus an emerging field which holds great promise for drug and
      biomarker discovery. Here we present a mass spectrometry-based approach for
      profiling of polar lipids, in particular phospholipids and sphingolipids, in
      Saccharomyces cerevisiae. The first step includes semi-quantitative surveys of
      lipids in an untargeted fashion, which is particularly powerful for detection of
      changes that cannot easily be anticipated. This leads to the identification of
      ions with increased or decreased signal intensities. Comprehensive theoretical
      calculation of the masses of yeast phospholipid and sphingolipid molecular
      species, based on fatty acyl and headgroup heterogeneity, is next used to
      tentatively assign ions of interest. Subsequent targeted analysis using tandem
      mass spectrometry allows for characterization and quantification of phospholipids
      and sphingolipids. Given the high degree of conservation in pathways of lipid
      metabolism between different organisms, it can be expected that this method will
      lead to the discovery of novel enzymatic activities and modulators of known ones,
      particularly when used in combination with genetic and chemogenetic libraries and
      screens. We validated the method using the EUROSCARF library of non-essential
      deletion mutants. Mutants of SCS7, a lipid hydroxylase, and SLC1, a putative acyl
      transferase with unknown substrate specificity, were profiled for their
      phospholipid and sphingolipid content. The observed changes in lipid profiles are
      consistent with previous observations and extend our knowledge on in vivo
      substrate use under permissive growth conditions.

PMID- 16652393
TI  - Autonomous cytoplasmic linear plasmid pPac1-1 of Pichia acaciae: molecular
      structure and expression studies.
AB  - The genome organization of the linear DNA-element pPac1-1 from Pichia acaciae was
      determined. It turned out to be the smallest autonomous cytoplasmic yeast plasmid
      known so far, consisting of only 12 646 bp, carrying the shortest terminal
      inverted repeats yet found (138 bp). As for other cytoplasmic linear yeast
      plasmids, it is characterized by a strikingly high A + T content (75.35%). Ten
      putative genes (open reading frames, ORFs) reside on the element, leaving only
      2.9% of the sequence outside a coding region. Highest similarities of the
      predicted proteins were obtained for proteins encoded by the three hitherto known
      autonomous cytoplasmic linear yeast plasmids. Amino acid sequences correspond to
      predicted polypeptides encoded by ORFs 2-11 of the linear plasmids pGKL2 of
      Kluyveromyces lactis, pSKL of Saccharomyces kluyveri and pPE1B of Pichia
      etchellsii. As for the latter, ORF1 existing on the two other plasmids is lacking
      on pPac1-1. Consistent with cytoplasmic localization, a cytoplasmic promoter
      termed upstream conserved sequence (UCS) is located in front of each reading
      frame. RT-PCR transcript analyses for ORFs 8, 9 and 11 proved expression of such
      genes but functions could not be attributed. The genome organization of pPac1-1
      and other autonomous linear elements was found to be almost congruent,
      irrespective of the accompanying smaller elements, which may or may not encode
      their own element-specific DNA polymerases.

PMID- 16652394
TI  - A new strategy for prenatal diagnosis of homozygous alpha(0)-thalassemia.
AB  - OBJECTIVES: We have shown previously that ultrasound examination performed by one
      experienced operator can be useful to exclude homozygous alpha(0)-thalassemia in
      a tertiary referral center. This study aimed to determine whether the technique
      was still applicable when performed by several operators and in different
      centers. METHODS: At the Maternal and Neonatal Hospital of Guangzhou (MNH) and
      Tsan Yuk Hospital of Hong Kong (TYH), women at risk of homozygous alpha(0)
      thalassemia were given the option of a non-invasive approach (using serial
      ultrasound examinations at 12-15, 16-20 and 25-30 weeks' gestation) to exclude an
      affected pregnancy. The fetal cardiothoracic ratio (CTR) was measured at each of
      these examinations and the placental thickness was measured at 12-15 weeks'
      gestation. The operators of MNH received training on the ultrasound examination
      techniques at TYH and the quality of the subsequent ultrasound examinations was
      checked regularly. The final diagnosis of homozygous alpha(0)-thalassemia was
      confirmed using an invasive test. RESULTS: Of 832 at-risk pregnancies studied in
      the two hospitals, 168 (20.2%) were affected. The overall sensitivity and
      specificity of the non-invasive approach was 100% and 95.6%, respectively. At
      MNH, the need for an invasive test was reduced by 80.8%, and all the affected
      pregnancies were diagnosed before 24 weeks' gestation. The results achieved at
      MNH were comparable with those at TYH. The at-risk pregnancies including the
      affected ones presented at a more advanced gestational age at MNH. At each
      hospital, one affected pregnancy was missed at the 12-week scan but this was
      subsequently detected at the 15-18-week scan. CONCLUSIONS: This non-invasive
      approach to exclude homozygous alpha(0)-thalassemia can be applicable when it is
      performed by several operators and in different centers.

PMID- 16652395
TI  - Placental volume measured by three-dimensional ultrasound in the prediction of
      fetal alpha(0)-thalassemia: a preliminary report.
AB  - OBJECTIVE: To evaluate the use of placental volume measured by three-dimensional
      (3D) ultrasound in predicting fetal homozygous alpha(0)-thalassemia (Hb-Bart's
      disease). METHODS: From June 2002 to May 2004 singleton pregnancies at risk of
      alpha(0)-thalassemia and normal controls were studied prospectively at 9-12 weeks
      of gestation. Affected fetuses were suspected to have alpha(0)-thalassemia by two
      dimensional (2D) ultrasound and confirmed by DNA analysis. Placental volume was
      measured on 3D ultrasound by a multiplanar technique. Intra- and interobserver
      agreement of measurements was assessed. The placental volume/crown-rump length
      quotient of the affected fetuses was compared with that of normal fetuses.
      RESULTS: The final study group comprised 105 pregnancies; 43 were at risk of
      alpha(0)-thalassemia and 62 were normal controls. Eleven (10.5%) fetuses were
      affected by alpha(0)-thalassemia, all from the at-risk group, and the others were
      normal. Intra- and interobserver agreement of volume measurement by 3D ultrasound
      was relatively poor; this was reflected in the wide limits of agreement, which
      ranged from -10.82 to 40.86 mL. The mean +/- SD placental volume/crown-rump
      length quotient in affected pregnancies was larger than that in unaffected
      pregnancies (1.37 +/- 0.65 vs. 1.13 +/- 0.39), but this difference was not
      significant (P > 0.05). CONCLUSIONS: Assessment of placental volume by 3D
      ultrasound does not seem to be superior to 2D ultrasound in the first-trimester
      prediction of alpha(0)-thalassemia.

PMID- 16652396
TI  - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX):
      report of the first prenatal mutation testing.

PMID- 16652397
TI  - Prenatal sonography and magnetic resonance imaging of pulmonary sequestration
      associated with a gastric duplication cyst.

PMID- 16652398
TI  - Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in
      rats.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) is a highly profibrogenic
      molecule implicated in hepatic fibrogenesis. Small interfering RNA (siRNA) is an
      effective tool to silence gene expression post-transcriptionally. Therefore, we
      conducted an investigation to determine if intraportal vein siRNA injection
      targeting CTGF inhibits CTGF expression on rat liver in vivo and furthermore
      whether it protects the liver from liver fibrosis. METHODS: Some rats received
      carbon tetrachloride (CCl4) by subcutaneous injections every three days for six
      consecutive weeks, and meantime they also obtained either siRNA (0.1 mg/kg)
      targeting CTGF, saline or a control siRNA by intraportal vein injection to rats'
      liver at the same pattern. Other rats received CCl4 by subcutaneous injection for
      2 weeks, followed by CCl4 and CTGF siRNA intraportal vein injection for four more
      weeks. RESULTS: Intraportal vein injection of CTGF siRNA specifically reduced the
      expression of CTGF protein in rat liver, and these effects were maintained for 3
      days. Six weeks after CCl4 injection, prominent upregulations were observed in
      the gene expressions of CTGF, type I, III collagen, laminin, tissue inhibitor
      metal proteinase-1 (TIMP-1) and transforming growth factor-beta1 (TGF-beta1) in
      saline or control siRNA-treated rats livers. Administrating CTGF siRNA for 4 or 6
      weeks, by contrast, markedly attenuated the induction of CTGF, type I, III
      collagen, laminin, TIMP-1 and TGF-beta1 genes, whereas Smad2, 7 gene expression
      was not affected. The number of active hepatic stellate cells (HSCs) determined
      by the expression of alpha-smooth muscle actin was also significantly decreased.
      The CTGF siRNA treatment markedly reduced serum procollagen type III, hepatic
      hydroxyproline and liver fibrosis staging. CONCLUSIONS: Silencing CTGF expression
      with siRNA demonstrates therapeutic potential to prevent liver fibrosis by
      inhibiting HSC activation with consequent extracellular matrix accumulation and
      the upregulation of TGF-beta1 gene expression.

PMID- 16652399
TI  - Ex vivo hypothermic recirculatory adenoviral gene transfer to the transplanted
      pig heart.
AB  - BACKGROUND: To facilitate the application of adenoviral gene therapy in clinical
      heart transplantation, we developed an ex vivo hypothermic recirculatory
      adenoviral gene transfer method to the transplanted pig heart. METHODS:
      Experimental animals were assigned into three groups; controls, 1x10(8) plaque
      forming units (pfu)/ml group and 1x10(9) pfu/ml group. During the 30 min gene
      transfer perfusion, 200 ml of University of Wisconsin solution containing the
      adenoviral vector was recirculated through the coronary vessels. The myocardial
      temperature was maintained below 4 degrees C and the perfusion pressure was
      adjusted at 50 mmHg. RESULTS: Cardiac myocyte transduction efficiencies in the
      1x10(8) pfu/ml group were 0.04% and 0.07%, whereas transduction efficiencies in
      the 1x10(9) pfu/ml group were widely distributed from 0.45% to 22.62%. The gene
      transduction efficiency increased with the virus titer. Additionally, no
      difference in the transduction efficiency was observed between different segments
      of the left ventricle. The current gene transfer method at 1x10(9) pfu/ml of
      adenovirus titer enabled homogeneous gene transduction into the transplanted pig
      heart up to a maximum of 22.62%. CONCLUSIONS: This model can be applied to a
      large isolated heart and will greatly facilitate the investigation of gene
      therapy in large animal models of heart transplantation.

PMID- 16652403
TI  - Fetal serum beta2-microglobulin as a marker for fetal infectious diseases.
AB  - OBJECTIVES: To evaluate whether fetal serum beta2-microglobulin could be used as
      a marker of fetal cytomegalovirus (CMV) or toxoplasmosis infection. METHODS:
      beta2-microglobulin was retrospectively assayed in fetal serum collected from 64
      patients with maternal infectious seroconversion (toxoplasmosis in 49 cases, CMV
      in 15). Using a beta2-microglobulin cutoff of 5 mg/L, infection and control
      groups were compared. RESULTS: Fetal serum beta2-microglobulin was >5 mg/L (5.2
      13.5 mg/L) in 12 of the 13 cases with proved fetal toxoplasmosis infection,
      indicating 90% sensitivity. In the 39 pregnancies with maternal seroconversion
      but no laboratory signs of fetal infection, fetal serum beta2-microglobulin was
      <5 mg/L, indicating 100% specificity. Fetal serum was >5 mg/L (6.3-32 mg/L) in 14
      of the 15 cases with proved fetal CMV infection, indicating 93.3% sensitivity.
      Specificity cannot be evaluated because maternal serum is not routinely screened
      for CMV during pregnancy. CONCLUSIONS: Fetal serum beta2-microglobulin is a
      reliable marker of fetal CMV or toxoplasmosis infection, which can be used in
      ambiguous situations. Because this increase is not specific, fetal serum beta2
      microglobulin would potentially be raised in other fetal infections.

PMID- 16652404
TI  - Fetal echocardiography during routine first-trimester screening: a feasibility
      study in an unselected population.
AB  - OBJECTIVE: To evaluate the feasibility of obtaining standard echocardiographic
      views of the fetal heart during routine first-trimester screening and construct
      reference ranges for cardiac biometry at 11 + 0 to 13 + 6 weeks of gestation.
      METHODS: A cross-sectional study of 584 fetuses in an unselected population.
      Viable pregnancies with a crown-rump length (CRL) of 41-78 mm were included.
      Echocardiography was performed by a single obstetrician using a 5 to 7.5 MHz
      vaginal transducer. The course and outcome of pregnancies were recorded and
      information on the babies was obtained in all cases. RESULTS: A completely
      satisfactory visualization of the fetal heart structures was possible in 58%
      (43%, 56% and 62% at 11, 12 and 13 weeks, respectively). Reference ranges were
      constructed from the measurements of cardiac ventricles, their outflow tracts,
      and cardiothoracic circumference ratio in relation to CRL. CONCLUSION: Standard
      echocardiograhic views of the fetal heart can be obtained at 11 + 0 to 13 + 6
      weeks of gestation using the transvaginal approach. New reference ranges were
      established for fetal cardiac biometry at 11 + 0 to 13 + 6 weeks of gestation.

PMID- 16652405
TI  - Congenital heart defects associated with fetal trisomy 18.

PMID- 16652406
TI  - Prenatal diagnosis of congenital immature teratoma arising from retroperitoneum.

PMID- 16652407
TI  - Placental volume in twin and triplet pregnancies measured by three-dimensional
      ultrasound at 11 + 0 to 13 + 6 weeks of gestation.
AB  - OBJECTIVE: To compare the placental volume at 11 + 0 to 13 + 6 weeks' gestation
      between singleton and multiple pregnancies and to examine the possible effect of
      chorionicity on placental volume. METHODS: The placental volume was measured by
      three-dimensional (3D) ultrasound using the Virtual Organ Computer-aided AnaLysis
      (VOCAL) technique in 290 consecutive twin and 37 triplet pregnancies at 11 + 0 to
      13 + 6 weeks of gestation. For the comparison of twin, triplet and singleton
      placental volumes each measurement was expressed as a multiple of the median
      (MoM) for singletons, previously established from the study of 417 normal fetuses
      at 11 + 0 to 13 + 6 weeks of gestation. RESULTS: Median twin and triplet
      placental volumes were 1.66 and 2.28 MoM for singletons, respectively. In twins
      the placental volumes increased significantly with gestation from a median of
      83.6 mL (5th and 95th centiles: 56.0 mL and 124.9 mL) at 11 + 0 weeks to 149.3 mL
      (5th and 95th centiles: 100.0 mL and 223.1 mL) at 13 + 6 weeks. The median MoM in
      monochorionic twins was not significantly different from that in dichorionic
      twins with fused placentas or dichorionic twins with separate placentas. In
      triplets the placental volumes increased significantly with gestation from a
      median of 114.9 mL (5th and 95th centiles: 77.6 mL and 170.1 mL) at 11 weeks to
      217.9 mL (5th and 95th centiles: 147.2 mL and 322.5 mL) at 13 + 6 weeks. There
      were no significant differences in total placental volume between monochorionic
      and dichorionic triplets, monochorionic and trichorionic triplets, or dichorionic
      and trichorionic triplets. CONCLUSIONS: Placental volume in multiple pregnancies
      does not depend on chorionicity, and the rate of placental growth between 11 and
      13 + 6 weeks is not significantly different between singletons, twins and
      triplets. Moreover, for a given gestational age the placental volume
      corresponding to each fetus in twins and triplets is 83% and 76%, respectively,
      of the placental volume in singletons.

PMID- 16652409
TI  - Debaryomyces hansenii--an extremophilic yeast with biotechnological potential.
AB  - We illuminate the ecological, physiological and genetic characteristics of the
      yeast Debaryomyces hansenii in the view of our belief that this metabolically
      versatile, non-pathogenic, osmotolerant and oleaginous microorganism represents
      an attractive target for fundamental and applied biotechnological research. To
      this end, we give a broad overview of extant biotechnological procedures using D.
      hansenii, e.g. in the manufacture of various foods, and propose research into the
      heterologous synthesis of a range of fine chemicals.

PMID- 16652410
TI  - Applications of functional magnetic resonance imaging in psychiatry.
AB  - While the use of MRI techniques has become a cornerstone of the neurology clinic,
      the application of such methods in psychiatry was rather limited until the advent
      of functional magnetic resonance imaging (fMRI). Over the past decade fMRI has
      superseded radionuclide-imaging techniques and blossomed into a widely used
      psychiatric research tool. This review focuses on the neurobiological findings
      from fMRI research in three less well-documented psychiatric disorders: attention
      deficit hyperactivity disorder (ADHD), depression, and obsessive-compulsive
      disorder (OCD). Although there was some disparity in early findings, greater
      standardization of image acquisition, analysis, and paradigms, and improved
      clinical classification are leading to a greater convergence of observations from
      different laboratories. fMRI is also beginning to realize its potential as an
      important mediator between genes and phenotypes, and may thus contribute to a
      better understanding of the pathophysiology of major neuropsychiatric diseases.
      The role of fMRI in the objective assessment of therapeutic intervention and
      early prediction of response to treatment is also discussed.

PMID- 16652412
TI  - Anti-tumor necrosis factor-alpha agents for rheumatoid arthritis: assessing
      longterm safety.

PMID- 16652413
TI  - The DAS is the most specific measure, but a patient questionnaire is the most
      informative measure to assess rheumatoid arthritis.

PMID- 16652414
TI  - Identifying those at risk of developing persistent pain following a motor vehicle
      collision.

PMID- 16652415
TI  - Classification in systemic sclerosis.

PMID- 16652416
TI  - Role of SLC22A4, SLC22A5, and RUNX1 genes in rheumatoid arthritis.
AB  - OBJECTIVE: Excessively suppressed expression of the SLC22A4 gene by RUNX1 is
      associated with the pathogenesis of rheumatoid arthritis (RA). Two etiological
      polymorphisms in the RUNX1 and SLC22A4 genes have been defined in a Japanese
      population. We studied additional polymorphisms to ascertain whether any
      SLC22A4/SLC22A5 haplotype is relevant for RA predisposition in a Spanish
      population. METHOD: We performed a case-control study comprising 416 patients
      with RA and 501 healthy subjects. RESULTS: The etiologic SLC22A4 mutation was
      rarely found in homozygosis (0.72% patients vs 0.40% controls). None of the 4
      haplotypes present in the SLC22A4/SLC22A5 region in 5q31 showed significant
      association with RA in our Spanish cohort. The causative RUNX1 variant found in a
      Japanese cohort displayed the same genotype distribution in our population.
      However, no difference was observed when allele or genotype frequencies were
      compared between Spanish patients with RA and controls. CONCLUSION: The SLC22A4
      and RUNX1 polymorphisms described as etiological in the Japanese study did not
      show a significant role in RA susceptibility in our population. The mechanism
      proposed by these Japanese investigators could underlie RA susceptibility
      irrespective of ethnicity, but the lower mutation rate present in our population
      hampered detection of a significant effect. Most probably the lack of mutated
      SLC22A4 substrate explains the absence of RUNX1 association with RA observed in
      our population.

PMID- 16652417
TI  - Controlled trial of methotrexate versus CH-1504 in the treatment of rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the clinical efficacy, safety, tolerability, and
      toxicity profile of a metabolically stable antifolate, CH-1504, compared to
      methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). METHODS: A 24
      week open-label trial of MTX and CH-1504 was performed in 20 patients with RA.
      RESULTS: Improvements in clinical and laboratory indicators were observed in both
      study groups. Improvement in the CH-1504 group was greater than in the MTX group.
      Both treatments were generally well tolerated; however, the liver function test
      abnormalities and gastrointestinal related adverse events expected with this
      class of medication were not seen with CH-1504. CONCLUSION: CH-1504 appears to be
      clinically efficacious and may possess a superior safety and tolerance profile
      compared to MTX.

PMID- 16652418
TI  - Safety of infliximab used in combination with leflunomide or azathioprine in
      daily clinical practice.
AB  - OBJECTIVE: To investigate the safety of infliximab (INF) combination therapy with
      leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis
      (RA). METHOD: A standardized questionnaire on the use of INF in combination with
      LEF or AZA was mailed to hospital physicians and collected over a 2 month period.
      Adverse events (AE) and the reasons for withdrawal of combination therapy were
      analyzed. RESULTS: Data on 225 patients with RA were collected retrospectively.
      INF was used in combination with LEF in 171 patients and with AZA in 54. The
      duration of INF exposure was similar in both groups (mean 8.8 mo). AE were
      reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations
      (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were
      infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion
      (5.3%), and skin reactions (4%). At the time the questionnaires were sent out,
      161 patients were continuing combination therapies. The main reasons for drug
      withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one
      temporary discontinuation for surgery. CONCLUSION: Our study suggests that INF
      used in combination with LEF or AZA could be an alternative to methotrexate/INF
      combinations.

PMID- 16652419
TI  - Patient's ethnicity does not influence utilization of effective therapies in
      rheumatoid arthritis.
AB  - OBJECTIVE: Biological agents have revolutionized the treatment of rheumatoid
      arthritis (RA). Given the previously documented ethnic disparity in the health
      service literature, we sought to determine if ethnic difference exists in the lag
      time between the diagnosis of RA and use of first biological agent. METHODS:
      RADIUS 1 and 2 are observational studies designed to document how rheumatologists
      treat RA across the United States. The sample analyzed here included early
      patients with RA who entered RADIUS with the initiation of the first biological
      agent. Ethnic status was categorized as White (W), African American (AA), and
      Hispanic (H). Lag time (months from RA diagnosis to initiation of the first
      biological agent) was the principal outcome variable. RESULTS: Compared to W
      (n=1616), AA (n=147) and H (n=116) were more likely to be female, younger, and
      have less than a high school education. Despite similar swollen and tender joint
      counts, AA and H had more active disease on the basis of Health Assessment
      Questionnaire and patient global assessments. Almost 97% of patients had some
      type of insurance coverage. On multivariable analysis, ethnic affiliation was not
      associated with lag time (14.5 months W vs 14.9 AA vs 14.3 H; p=NS). Similarly,
      there were also no significant ethnic differences in time to first DMARD (e.g.,
      methotrexate) initiation. CONCLUSION: In a national sample of patients with RA,
      most of whom were insured, the length of time from diagnosis of RA to initiation
      of the first biological agent was not significantly different among Whites,
      African Americans, and Hispanics.

PMID- 16652420
TI  - Survival analysis and longterm results of elbow synovectomy in rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate longterm results and survival rate of open synovectomy of
      the elbow joint in patients with rheumatoid arthritis (RA). METHODS: Between 1986
      and 2000, synovectomy of the elbow was performed on 103 joints in 92 patients
      with RA. Eighty-five joints were included in this study. Mean age at time of
      surgery was 52 years (range 13 to 62 yrs). On 13 elbows with Larsen stage I and
      II disease, early synovectomy preserving the radial head was performed; in 72
      cases with Larsen stage III and IV, late synovectomy with radial head resection
      was necessary. RESULTS: In early synovectomy, one joint received prosthetic joint
      replacement and 2 joints underwent resynovectomy a mean of 9 years after primary
      surgery. The survival rate (no further operations) was 91% after 5 years and 78%
      after 10 years. In late synovectomy, 16 elbow joints were operated again a mean
      of 4.6 years after primary surgery (10 prosthetic joint replacements, 2 resection
      interposition arthroplasties, 4 resynovectomies). Survival rate was 82% after 5
      years and 66% after 10 years. Sixty-one elbows were examined clinically at a mean
      followup period of 8.7 years (range 2.8-17.3 yrs). There was a significant
      improvement of the Morrey score at followup, especially due to effective relief
      of pain. Improvement of joint motion was seen in late synovectomy for pronation
      and supination. The mean preoperative Larsen stage was 3.11, which decreased
      significantly to 3.66 at followup. CONCLUSION: Our findings suggest that
      synovectomy is a safe and effective procedure in differential treatment of RA of
      the elbow.

PMID- 16652421
TI  - Role of endothelial damage in the pathogenesis of interstitial pneumonitis in
      patients with polymyositis and dermatomyositis.
AB  - OBJECTIVE: Polymyositis and dermatomyositis (PM/DM) are often complicated by
      interstitial pneumonitis (IP), which is an important cause of death. It has been
      reported that blood concentration of transforming growth factor-beta (TGF-beta),
      which is produced by a wide range of cells including endothelial cells and
      enhances the fibrotic changes in various tissues, is increased in PM/DM with IP.
      Endothelial damage is likely to exist in PM/DM. We studied the relationship
      between endothelial damage and IP in PM/DM. METHODS: Blood levels of sialylated
      carbohydrate antigen KL-6, TGF-beta, endothelin-1 (ET-1), thrombomodulin (TM),
      and plasminogen activator inhibitor-1 (PAI-1) were determined in 43 patients with
      PM or DM with or without IP, and the relationship between these measures was
      analyzed. RESULTS: Blood levels of KL-6 and TGF-beta were higher in the patients
      with IP than those without, and these measures were well correlated with each
      other. Levels of ET-1, TM, and PAI-1, all known to reflect the extent of
      endothelial damage, were also increased in patients with IP, and these measures
      correlated well with TGF-beta. CONCLUSION: Our data suggest that endothelial
      damage might play an important role through the production of fibrosis-enhancing
      factors such as TGF-beta or ET-1 in PM/DM.

PMID- 16652422
TI  - Cepharanthin, a biscoclaurine alkaloid, prevents destruction of acinar tissues in
      murine Sjogren's syndrome.
AB  - OBJECTIVE: Our previous study suggested that suppression by cepharanthin of tumor
      necrosis factor-a (TNF-a)-induced matrix metalloproteinase-9 (MMP-9) could
      prevent destruction of the acinar structure in the salivary glands of patients
      with Sjogren's syndrome (SS). In this study, we observed that in vivo
      administration of cepharanthin prevented severe damage to acinar tissues in the
      murine model of human SS. METHODS: Cepharanthin was intraperitoneally
      administered to thymectomized female NFS/sld mice. Inflammatory lesions in the
      salivary and lacrimal glands were then examined histologically. Expression of
      phosphorylated IkB-a, MMP-9, and type IV collagen was analyzed
      immunohistochemically. The apoptotic cell death of acinar cells was determined.
      RESULTS: Although extensive mononuclear cell infiltration and destruction of
      acinar tissue in salivary and lacrimal glands were observed in control mice,
      significant improvement of these lesions was evident in mice treated with
      cepharanthin. Immunohistochemical analysis revealed that p65, phosphorylated IkB
      a, and MMP-9 were more strongly stained in the acinar cells of control mice than
      in cepharanthin-treated mice. Although no staining for type IV collagen was
      observed in the acinar tissues of control mice, continuity of staining for type
      IV collagen was observed in acinar tissues of cepharanthin-treated mice.
      Destruction of acinar tissues was attributed to the induction of apoptosis,
      suggesting that cepharanthin inhibits apoptosis by suppressing phosphorylation of
      IkB-a, followed by prevention of MMP-9 activation. CONCLUSION: Our findings
      suggest that cepharanthin may be a promising agent for use in preventing
      destruction of acinar tissues in murine SS.

PMID- 16652423
TI  - Characterization of an activation factor released from human neutrophils after
      stimulation by triclinic monosodium urate crystals.
AB  - OBJECTIVE: To determine the presence and characterize the activity of a soluble
      activation factor rapidly released by human neutrophils after stimulation with
      monosodium urate (MSU) crystals. METHODS: Supernatants from human neutrophils
      stimulated by MSU crystals for 5 to 60 min were tested for their ability to
      stimulate a chemotactic response, induce a mobilization of calcium, and increase
      the tyrosine phosphorylation levels in naive neutrophils. RESULTS: Supernatant
      from neutrophils stimulated <or= 15 min by MSU crystals was chemotactic for
      neutrophils, induced a mobilization of calcium, and increased the levels of
      tyrosine phosphorylation in fresh neutrophils. Generation of activity in the
      supernatant was independent of protein synthesis and was eliminated after
      digestion with trypsin. Leukotriene B4 (LTB4), platelet-activating factor (PAF),
      and formyl peptide receptor antagonists as well as neutralizing anti-interleukin
      8 (IL-8) antibodies did not inhibit the chemotactic activity in the supernatant,
      although pertussis toxin did inhibit the mobilization of calcium observed in
      response to the supernatant. Stimulation of neutrophils with formyl-methionine
      leucine-phenylalanine, IL-8, and LTB4 inhibited subsequent mobilization of
      calcium by the supernatant. CONCLUSION: There is rapid liberation of a potent
      activation signal from neutrophils after interaction with MSU crystals. This
      activation factor can further stimulate surrounding neutrophils and contribute to
      amplification of the inflammatory response induced by MSU crystals.

PMID- 16652424
TI  - Ambulatory physical activity, disease severity, and employment status in adult
      women with osteoarthritis of the hip.
AB  - OBJECTIVE: To measure ambulatory physical activity and determine associations
      between physical inactivity and joint function, gait function, disease severity,
      and employment status in adult women with hip osteoarthritis (OA) living in the
      community. METHODS: Sixty-five adult women with hip OA were recruited from an
      outpatient clinic. Ambulatory physical activity was measured using an activity
      monitor based on an accelerometer over 7 days, which estimated step counts, net
      energy expenditure, and time spent in activity by acceleration intensity. The
      Harris hip score, walking speed, and radiographic stage were assessed for joint
      function, gait function, and disease severity, respectively. Employment status
      was classified into unemployed and employed (sitting occupations and
      standing/walking occupations). RESULTS: More than 40% of patients were classified
      as inactive, with less time spent in moderate-intensity activity (median 5.6 vs
      22.9 min/day) compared with their counterparts. Employment status and the
      presence or absence of stage 4 (endstage) arthritis were independently associated
      with activity classification, and there was an interaction between these 2
      variables; i.e., although stage 4 arthritis was associated with inactivity in
      patients who were unemployed, it bore no relationship in patients who were
      employed. CONCLUSION: A significant proportion of adult women with hip OA were
      physically inactive, with a lack of moderate-intensity activity. The possible
      interaction between endstage OA and employment status requires further study to
      determine whether being at work negates the adverse effects of endstage OA or
      whether higher functioning due to physical activity enables patients with
      endstage OA to be employed.

PMID- 16652425
TI  - Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis
      of the knee.
AB  - OBJECTIVE: Intraarticular (IA) hylan injections constitute second-line therapy
      for osteoarthritis (OA) of the knee, but human studies suggesting a possible
      mechanism of action are lacking. We examined the effect of IA Hylan GF-20
      injections on synovial fluid (SF) hyaluronan (HA) concentration, viscosity, and
      elasticity over a 6-month period in patients with mild to moderate OA of the
      knees. METHODS: Patients with symptomatic knee OA (Osteoarthritis Research
      Society International grade 1-2) had SF aspirated from the study knee pre- and 3
      and 6 months post-Hylan injection. Primary endpoints included SF HA
      concentration, viscosity, and elasticity. SF HA concentration was determined
      using uronic acid assay, and rheology measured using a micro-Fourier rheometer.
      RESULTS: Sequential SF samples were available from 32 of 60 subjects injected at
      baseline (15 men, 17 women; mean age 65 yrs) at 3 months post-injection. The mean
      HA concentration had increased by 13% (p<0.0008), and the complex shear modulus
      had increased by 16% (p<0.03). Sufficient SF was also available from 19 of these
      subjects at 6 months post-injection when mean HA concentration was 2.24+/-0.62
      mg/ml compared to their baseline mean of 2.02+/-0.52 mg/ml, an increase of 10%
      (p<0.053). CONCLUSION: This open-label study showed a statistically significant
      change from baseline in both SF HA concentration and complex shear modulus at 3
      months following IA Hylan GF-20 injection among subjects with mild to moderate
      knee OA. These results suggest that one possible mechanism of action of
      viscosupplementation is to promote endogenous HA production. Longer-term studies
      are required to identify whether these changes in SF measures are important for
      modification of disease progression in knee OA.

PMID- 16652426
TI  - A prospective, randomized, double-blind, placebo controlled study to evaluate the
      efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee.
AB  - OBJECTIVE: To assess the efficacy of intraarticular (IA) injections of hyaluronic
      acid (HA) compared to placebo in patients with osteoarthritis (OA) of the knee;
      and to assess patient satisfaction with treatment relative to placebo, and
      whether there is a difference between a series of 3 versus 6 consecutive IA
      injections. METHODS: We conducted a randomized, double-blind, placebo controlled,
      2-arm parallel design trial of 106 patients with radiologically confirmed knee
      OA. Two-milliliter IA injections using 20 mg/ml HA sodium salt or saline placebo
      were administered once weekly over 3 weeks (HA and placebo groups), followed by
      once weekly IA injection with 2.0 ml (20 mg/ml) HA for a further 3 consecutive
      weeks. The primary efficacy assessment included Western Ontario and McMaster
      Universities osteoarthritis index (WOMAC) score for knee pain (Week 3 score).
      Secondary efficacy assessments included WOMAC scores for knee pain at Weeks 6 and
      12 (followup), as well as WOMAC stiffness, physical function and quality of life
      scores, visual analog scale (VAS) scores for pain at rest and following walking
      and stepping activity, range of knee joint motion, and global patient
      satisfaction with treatment and quality of life using the SF-36. RESULTS: After 3
      weeks of study treatment, both treatment groups showed improvements in knee
      function, the HA group showing a greater improvement compared to placebo in WOMAC
      knee pain score (p < 0.01). The HA group showed greater (p < 0.05) improvement in
      the overall WOMAC score and VAS pain following walking and stepping activity at
      Week 3. Results from all other secondary efficacy assessments at Weeks 6 and 12
      including patient satisfaction were similar and were not statistically
      significant between treatment groups, and there were no significant differences
      between groups for adverse events. CONCLUSION: Intraarticular HA was superior to
      placebo in improving knee pain and function, with no difference between 3 or 6
      consecutive injections for the primary efficacy assessment.

PMID- 16652427
TI  - Medicinal and injection therapies for mechanical neck disorders: a Cochrane
      systematic review.
AB  - OBJECTIVE: To systematically review randomized trials on medicines and injections
      used to improve pain, function/disability, and patient satisfaction in adults
      with mechanical neck disorders (MND) with or without associated headache or
      radicular findings. METHODS: We searched CENTRAL (Issue 4, 2002), and MEDLINE,
      EMBASE, MANTIS, CINHAL from their start to March 2003. Two authors independently
      selected articles, abstracted data, and assessed methodological quality using the
      Jadad criteria. When clinical heterogeneity was absent, we combined studies using
      random-effects metaanalysis models. RESULTS: Thirty-two selected trials had an
      overall methodological quality of mean 3.2/5. For acute whiplash, administering
      intravenous methylprednisolone within 8 hours reduced pain at one week [SMD -0.90
      (95% CI -1.57 to -0.24)], and sick leave but not pain at 6 months compared to
      placebo. For chronic MND at short-term followup, intramuscular injection of
      lidocaine was superior to placebo [SMD 1.36 (95% CI -1.93 to -0.80)]. In chronic
      MND with radicular findings, epidural methylprednisolone and lidocaine reduced
      neck pain [SMD -1.46 (95% CI -2.16 to -0.76)] and improved function at one-year
      followup compared to the intramuscular route. In subacute/chronic MND, we found
      conflicting evidence for oral psychotropic agents. In chronic MND with or without
      radicular findings or headache, there was moderate evidence from 5 high quality
      trials showing that botulinum toxin (Botox A) intramuscular injections were not
      better than saline in improving pain [SMD pooled -0.39 (95% CI -1.25 to 0.47)],
      disability, or global perceived effect. CONCLUSION: Intramuscular injection of
      lidocaine for chronic MND and intravenous injection of methylprednisolone for
      acute whiplash were effective treatments. There was limited evidence of
      effectiveness of epidural injection of methylprednisolone and lidocaine for
      chronic MND with radicular findings. Muscle relaxants and nonsteroidal
      antiinflammatory drugs have unclear benefits. There was moderate evidence that
      Botox-A intramuscular injections for chronic MND were not better than saline.

PMID- 16652428
TI  - Alberta rodeo athletes do not develop the chronic whiplash syndrome.
AB  - OBJECTIVE: To determine if an unselected group of rodeo athletes would report a
      more benign outcome to their motor vehicle whiplash injuries than a group of
      spectators at rodeo events. METHODS: This survey compares the self-reported
      outcome of motor vehicle collision whiplash injuries (neck and/or back sprain) in
      rodeo athletes and spectators attending rodeo events. Subjects were asked to
      recall motor vehicle collision experiences, the type of vehicle they were in, the
      presence of symptoms as a result, and outcomes for those symptoms. RESULTS: Forty
      seven percent of rodeo athletes and 59% of spectators recalled being in a motor
      vehicle collision. A total of 33% of rodeo athletes who had collisions recalled
      acute symptoms they associated with the collision compared to a recall of
      symptoms in 61% of spectators who had collisions. Vehicle types during collisions
      and occupation type at time of the survey were the same for both groups. Duration
      of symptoms, however, was 30 days (+/- 14 days) in rodeo athletes and 73 days (+/
      61 days) in spectators. None of the rodeo athletes recalled symptoms lasting for
      more than 60 days compared to 15% of spectators who had symptoms more than 60
      days. Rodeo athletes took no more than 3 weeks off work, whereas among
      spectators, it was common to take more than 6 weeks off. CONCLUSION: Rodeo
      athletes appear to be in at least as many motor vehicle collisions as rodeo
      spectators, and 33% suffered the acute whiplash syndrome. Rodeo athletes appear,
      however, to be more resistant than spectators to developing prolonged pain and
      disability.

PMID- 16652429
TI  - Clinical significance of decreased serum concentration of cartilage oligomeric
      matrix protein in systemic juvenile idiopathic arthritis.
AB  - OBJECTIVE: Serum cartilage oligomeric matrix protein (COMP) concentration is
      elevated in patients with early osteoarthritis and early rheumatoid arthritis,
      and may be a biomarker of cartilage turnover. We investigated whether serum COMP
      concentration could be a clinically significant marker of arthritis and/or growth
      impairment in juvenile idiopathic arthritis (JIA). METHODS: Specimens were
      collected from 82 healthy blood donors under 22 years of age with no growth
      impairment who served as healthy controls, and from 24 patients with JIA (6 with
      oligoarthritis, 10 with polyarthritis, 8 with systemic JIA) presenting with
      active arthritis. Serum COMP concentration was determined using a human COMP
      assay kit. RESULTS: Serum COMP concentrations were significantly higher in all
      controls less than 16 years of age than in all controls aged 16 years or older.
      There was a significant negative correlation between serum COMP concentration and
      serum C-reactive protein in patients with JIA. Serum COMP concentrations in
      patients with systemic JIA were significantly lower than those in controls.
      CONCLUSION: Serum COMP concentrations in healthy children reflected increased
      cartilage turnover in the growth phase. Because the serum COMP concentration was
      decreased in cases of systemic JIA in which growth impairment was pronounced, the
      systemic inflammation occurring in systemic JIA may have an effect on cartilage
      turnover, which plays an important role in growth. Serum COMP concentration may
      prove to be a marker that indicates growth impairment in systemic JIA.

PMID- 16652430
TI  - Bone mineral density and turnover in non-corticosteroid treated African American
      children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To determine bone mineral content (BMC), bone mineral density (BMD), Z
      scores, and markers of bone turnover in African American children with juvenile
      rheumatoid arthritis (JRA). METHODS: Eight children with JRA with no prior
      exposure to corticosteroids were evaluated. Lumbar spine (L1-L4) and total body
      and total hip BMC and BMD were determined using dual x-ray absorptiometry (DXA),
      and Z scores (BMD) were calculated. Serum samples of markers of bone turnover
      including pyridinoline (PYR), N-terminal propeptide of type I procollagen (P1NP),
      osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP) were measured.
      RESULTS: The mean Z score (BMD) at the lumbar spine (L1-L4) in patients with JRA
      was -1.2+/-0.8. Z scores for total body and total hip were within 1 standard
      deviation of normal compared with healthy historical controls matched for age,
      sex, and race. CONCLUSION: BMD was normal for chronological age (defined as Z
      score >or= 2.0) in African American children with JRA who had not previously been
      treated with corticosteroids. Further studies are needed on the effects of JRA on
      skeletal health in African American children.

PMID- 16652431
TI  - Tumor necrosis factor-alpha inhibition and VATER association: a causal
      relationship.
AB  - Inflammatory conditions that may require the use of a tumor necrosis factor-a
      (TNF-a) antagonist often involve women of child-bearing age. TNF-a antagonists
      are presumed to be safe in pregnancy based on animal data. However, this has
      never been formally studied in prospective trials involving humans. We describe a
      patient with psoriasis and psoriatic arthritis who took etanercept 50 mg
      subcutaneously (SQ) twice weekly throughout her pregnancy. She gave birth to a
      child with VATER association. Animal and human data exist to suggest a possible
      causal relationship between the mother's use of etanercept and the child's
      development of VATER association. We propose that the TNF antagonists,
      specifically etanercept, be used with caution in pregnant women. Patient
      registries of women who take TNF-a antagonists during pregnancy also need to be
      followed to see if there is an increase in the birth defects that are part of
      VATER association.

PMID- 16652432
TI  - Regulation of killer immunoglobulin-like receptors in systemic lupus
      erythematosus.

PMID- 16652433
TI  - Angry fat.

PMID- 16652434
TI  - Neck injury and fibromyalgia-- are they really associated?
AB  - OBJECTIVE: To investigate whether whiplash injury may be a trigger for the onset
      of fibromyalgia (FM). METHODS: One hundred fifty-three patients presenting to the
      emergency room with the diagnosis of whiplash injury were examined. The control
      group included 53 patients hospitalized with fractures of the limbs, spine, and
      ribs due to road accident. The study and control groups were interviewed shortly
      after presenting and then followed prospectively. Patients complaining of
      musculoskeletal symptoms during followup were examined and a count of 18 tender
      points was conducted. FM was diagnosed if the patient fulfilled currently
      accepted 1990 American College of Rheumatology criteria. RESULTS: The mean
      followup period for the study and control groups was 14.5 months (range 12-18)
      and 9 months (range 6-14), respectively. There were no differences between the
      groups with regard to age, sex, marital, education, or employment status. During
      the followup period only one patient in the study group and no patients in the
      control group developed signs and symptoms of FM. Three patients in the study
      group (2%) and 15 patients in the control group (16%) filed insurance claims;
      none was associated with FM. CONCLUSION: Whiplash injury and road accident trauma
      were not associated with an increased rate of FM after more than 14.5 months of
      followup.

PMID- 16652435
TI  - Licofelone reduces progression of structural changes in a canine model of
      osteoarthritis under curative conditions: effect on protease expression and
      activity.
AB  - OBJECTIVE: We investigated the effectiveness of licofelone, a combined 5
      lipoxygenase and cyclooxygenase inhibitor, on structural changes in the anterior
      cruciate ligament (ACL) experimental dog model of osteoarthritis (OA) under
      therapeutic conditions. The effect of drug treatment on the expression and
      activity of metalloproteases in the OA cartilage was also studied. METHODS: The
      cranial cruciate ligament of the right stifle joint was surgically sectioned in
      14 dogs to create OA lesions. Of these dogs, 7 received placebo treatment and
      served as OA controls, while 7 were treated with licofelone 2.5 mg/kg twice daily
      for an 8-week period, starting 4 weeks after surgery. At necropsy, macroscopic
      evaluations were made of the size of osteophytes and the severity of cartilage
      lesions on femoral condyles and tibial plateaus. Collagenase and other
      metalloprotease activity levels in cartilage were measured. Levels of gene
      expression of matrix metalloprotease (MMP-1), MMP-13, cathepsin K, and ADAMTS-5
      were quantified by RT-PCR. RESULTS: Licofelone treatment reduced the development
      of osteophytes and size of cartilage lesions on the femoral condyles and on the
      tibial plateaus (p < 0.04). Drug treatment also significantly decreased
      collagenase (p < 0.02) and metalloprotease (p < 0.04) activities, as well as the
      levels of gene expression of MMP-1 (p < 0.01), MMP-13 (p < 0.05), cathepsin K,
      and ADAMTS-5 (p = 0.01). CONCLUSION: Under therapeutic conditions licofelone
      showed the ability to reduce the progression of structural changes in
      experimental dog OA. This beneficial effect is likely mediated through decrease
      in the synthesis of a number of catabolic factors, including proteolytic enzymes,
      involved in cartilage breakdown.

PMID- 16652436
TI  - Associations between joint space narrowing and molecular markers of collagen and
      proteoglycan turnover in patients with knee osteoarthritis.
AB  - OBJECTIVE: We examined whether plasma concentrations of biomarkers of the
      collagenase cleavage of type II collagen (C2C), types I and II collagens (C1,2C),
      type II collagen synthesis (CPII), proteoglycan aggrecan turnover (CS846), and
      the ratio C2C:CPII would distinguish subjects with progressive radiographic
      osteoarthritis (OA) from those with stable disease. METHODS: Subjects were 120
      obese middle-aged women with unilateral knee OA who participated in a 30-month
      clinical trial of structure modification with doxycycline, in which a
      standardized semiflexed anteroposterior view of the knee was obtained at
      baseline, 16 months, and 30 months. Subjects were selected from a larger sample
      to permit a priori comparisons between 60 OA progressors and 60 nonprogressors,
      as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment.
      Each group contained 30 subjects who exhibited clinically significant increases
      in knee pain over 30 months and 30 who did not. Plasma samples were obtained
      every 6 months for determination of C2C, CPII, CS846, and C1,2C. RESULTS: None of
      the biomarkers was a significant predictor of progression of JSN. Over the
      interval from baseline to 16 months, the mean and the maximum of the intercurrent
      CS846 values were significantly associated with JSN (i.e., 0.12-0.14 mm of JSN
      per SD decrease in mean or maximum CS846; p < 0.01). The mean of serial CS846
      levels was related to JSN also during the interval between months 16 and 30.
      CONCLUSION: Markers of type II collagen synthesis/degradation and of proteoglycan
      aggrecan turnover were not predictive of JSN in knee OA in this pilot study.
      However, serial concentrations of proteoglycan aggrecan epitope CS846 were
      associated with JSN during both the intervals studied.

PMID- 16652437
TI  - Adalimumab for treating rheumatoid arthritis.
AB  - OBJECTIVE: To assess the efficacy and safety of adalimumab in the treatment of
      rheumatoid arthritis (RA). METHODS: A Cochrane systematic review was performed.
      The literature search, selection and assessment of the methodological quality of
      the studies, and the data extraction were performed according to the standard
      methodology of the Cochrane reviews. Outcome measures included American College
      of Rheumatology (ACR) and European League Against Rheumatism responses, Disease
      Activity Score 28 and components of the ACR response, and radiographic and safety
      data. Weighted mean difference and relative risk were used for reporting
      continuous and dichotomous data, respectively. Number needed to treat (NNT) or to
      harm (NNH) were estimated when appropriate. When significant heterogeneity was
      not found, data were pooled. RESULTS: Six studies with 2,390 patients were
      included in this review. With adalimumab 40 mg every other week (eow) +
      methotrexate versus placebo + methotrexate, the absolute risk differences to
      achieve an ACR20, ACR50, and ACR70 response at 52 weeks were 35%, 32%, and 19%
      with NNT of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg eow
      and 20 mg every week (ew) significantly slowed the radiological progression. With
      adalimumab 40 mg eow versus placebo, the absolute risk differences to achieve an
      ACR20, ACR50, and ACR70 response at 24/26 weeks were 23.64%, 15.31%, and 12.22%
      with NNT of 5.0, 7.0, and 9.0, respectively. In most of the analyzed studies and
      comparisons, there were no significant differences in safety outcomes between
      adalimumab and control groups. CONCLUSION: On the basis of studies reviewed here,
      adalimumab is efficacious in the treatment of RA. No serious adverse effects
      occurred.

PMID- 16652439
TI  - Crossroads of B cell activation in autoimmunity: rationale of targeting B cells.
AB  - B cells have historically been considered as not preferentially involved in the
      immunopathogenesis of inflammatory joint diseases, in particular rheumatoid
      arthritis (RA), despite the notion that autoantibodies and immune complexes were
      involved in pathogenesis and served as diagnostic and classification markers.
      Following initial reports that patients with non-Hodgkin's lymphoma (NHL) and
      coexisting RA showed improvement in signs and symptoms of RA after anti-CD20
      therapy, the role of B cells in autoimmune diseases was reexamined. Potential
      mechanisms can be inferred from what is known about the role of B cell functions,
      in particular antigen-experienced memory B cells. Activation of these cells can
      be dependent on T lymphocytes or independent of them. Once activated, the cells
      can efficiently act as antigen-presenting cells, can produce inflammatory
      cytokines, and may alternatively differentiate into antibody-producing plasma
      cells. These processes contribute to the activation of other immune cells and
      ultimately to joint destruction in RA. The development and maintenance of RA may
      be related to both direct and indirect involvement of these B cell-dependent
      processes. In systemic lupus erythematosus (SLE), the central pathogenic
      importance of autoimmune B cells is well recognized, based on early recognition
      of numerous autoantibodies and clinically important immune complexes. Based on
      the evidence supporting B cell involvement in the pathophysiology of autoimmune
      diseases, investigations are evaluating the clinical impact of B cell targeted
      therapies. B cell targeted therapies in human trials include an anti-B lymphocyte
      stimulator protein agent, belimumab; an anti-CD20 agent, rituximab; and an anti
      CD22 antibody, epratuzumab.

PMID- 16652440
TI  - Updates from B Cell Trials: Efficacy.
AB  - Recent reports of data from ongoing trials have contributed substantially to our
      growing understanding of the potential effectiveness and safety of B cell
      targeted therapy in the treatment of rheumatic diseases. In addition, the results
      have addressed practical questions regarding the administration of specific
      agents. Phase II trials of rituximab (RTX) have provided data supporting efficacy
      in rheumatoid arthritis (RA), including more clearly defining the role of
      glucocorticoids in the treatment and exploring the doses necessary to improve the
      signs and symptoms of RA. The Phase IIb Dose-Ranging Assessment International
      Clinical Evaluation of Rituximab in RA (DANCER) trial demonstrated that a
      significant percentage of patients achieved clinical improvement when treated
      with different doses of RTX as compared with those given placebo. The Phase III
      Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) trial
      demonstrated efficacy of RTX in patients with a history of nonresponse to tumor
      necrosis factor inhibitors. Preliminary results of a small cohort of patients
      receiving RTX retreatment demonstrated efficacy with repeat administration. Phase
      II results of another B cell targeted therapy, anti-B lymphocyte stimulator
      protein, demonstrated efficacy. The efficacy of the agent, belimumab, resulted in
      an ACR20 response that was significantly higher in patients treated with
      belimumab versus placebo and in patients with RA. These findings support the
      hypothesis that B cells play an integral role in the pathogenesis of RA, and this
      report will review the efficacy results of clinical trials targeting B cells.

PMID- 16652441
TI  - B cell targeted therapies: safety considerations.
AB  - Reported data from recent clinical trials have contributed substantially to our
      growing understanding of the potential effectiveness and safety of B cell
      targeted therapy in the treatment of rheumatic diseases. Trials with rituximab,
      an anti-CD20 monoclonal antibody that depletes mature B cells, have amassed the
      most data of any B cell targeted therapy to date. A number of other B cell
      directed therapies are under investigation. Interestingly, although they may
      share a common target, the different agents have quite distinct mechanisms of
      action, and therefore their efficacy and safety profiles may differ. A common
      concern with all B cell directed therapies is the potential effect these agents
      may have on humoral immunity. The safety profile of rituximab in the oncology
      setting is well known, based on a database of well over 370,000 patients. Phase
      II trials of rituximab in rheumatoid arthritis (RA) have begun to examine safety
      issues specifically in the RA population, including issues surrounding longterm
      and repeated treatment safety profiles. Questions about the longterm safety of B
      cell therapy remain to be clarified: What will be the safety profile for repeated
      treatment courses? What will be the safety profile when B cell targeted therapies
      are used in sequence or in conjunction with other agents? Answers to these
      important questions are likely to come from careful observations by treating
      clinicians, data from registries, and longterm followup of patients enrolled in
      clinical trials.

PMID- 16652442
TI  - B cell targeted therapies in autoimmune diseases.
AB  - In addition to rheumatoid arthritis (RA), B cells are likely to play a
      significant role in the development of other autoimmune rheumatic diseases, such
      as systemic lupus erythematosus (SLE), myositis, and vasculitis. Small-vessel
      vasculitis subtypes may be immune complex-mediated (cryoglobulinemia) or
      antineutrophil cytoplasmic antibody (ANCA)-associated; ANCA may be involved in
      the pathogenesis of vasculitis. In SLE, both antibody-associated and antibody
      independent processes are almost certainly involved. B cell activity and
      autoantibody production are increased, while patients often have reduced
      peripheral B cells and abnormal B cell profiles. B lymphocyte stimulator (BLyS)
      protein regulates B cell activation and differentiation. For these reasons, B
      cells and the molecules that activate them are potential therapeutic targets in
      these diseases. Recent clinical trial data from small studies of rituximab (RTX)
      in SLE suggest that treatment improved clinical variables and measures of disease
      activity in patients, including those with central nervous system SLE. With
      retreatment, patients whose B cells were successfully depleted continued to show
      improvement in clinical and laboratory variables. Preliminary data suggest that
      treatment with RTX may be effective in ANCA-associated vasculitis. In addition a
      recent study showed significant benefit with myositis. Although these studies
      contain small cohorts of patients, they demonstrate that B cell-modulating
      therapies show promise in treatment of a variety of autoimmune diseases.

PMID- 16652443
TI  - Preliminary study finds brain training can reduce pain.

PMID- 16652444
TI  - Tinnitus. Overcoming the noise.

PMID- 16652445
TI  - How common is celiac disease?

PMID- 16652446
TI  - Can I catch a sexually transmitted disease from a toilet seat?

PMID- 16652447
TI  - What now for biotechnology?

PMID- 16652448
TI  - Mentoring mismatch.

PMID- 16652449
TI  - Mass uprising of women in science.

PMID- 16652450
TI  - Preventing the incurable: Asian rabies experts advocate rabies control.

PMID- 16652451
TI  - Readers' responses to "in the wake of Katrina: a surgeon's first-hand report of
      the New Orleans tragedy".

PMID- 16652452
TI  - Readers' responses to "in the wake of Katrina: a surgeon's first-hand report of
      the New Orleans tragedy".

PMID- 16652453
TI  - Veterinary Oncology Research Cooperative.

PMID- 16652454
TI  - Readers' responses to "are 80 hours a week enough to train a surgeon?".

PMID- 16652455
TI  - Proceedings of the American Association of Orthodontics 2nd Early Treatment
      Symposium. Las Vegas, Nevada, USA, 21-23 January 2005.

PMID- 16652456
TI  - Clinical photographic quiz. Foreign body impacted in the larynx.

PMID- 16652457
TI  - Clinical photographic quiz. Provision of an artificial airway.

PMID- 16652458
TI  - Clinical photographic quiz. Ranula.

PMID- 16652459
TI  - Clinical photographic quiz. None of the above.

PMID- 16652460
TI  - Clinical photographic quiz. Incisional biopsy and histology.

PMID- 16652461
TI  - Clinical photographic quiz. Thyroglossal cyst.

PMID- 16652463
TI  - FOREWORD.

PMID- 16652462
TI  - Clinical photographic quiz. The intimate relationship between the tract and the
      body of the hyoid bone.

PMID- 16652464
TI  - EFFECTS OF CORRELATION BETWEEN VEGETATIVE AND REPRODUCTIVE FUNCTIONS IN THE
      TOMATO (LYCOPERSICON ESCULENTUM MILL.).

PMID- 16652465
TI  - THE EXTRACTION OF PLANT TISSUE FLUIDS AND THEIR UTILITY IN PHYSIOLOGICAL STUDIES.

PMID- 16652466
TI  - SOME OBSERVATIONS ON THE GROWTH OF YEAST.

PMID- 16652467
TI  - SULPHUR IN RAINWATER.

PMID- 16652468
TI  - A PLANT PHOTOMETER.

PMID- 16652470
TI  - NOTES.

PMID- 16652469
TI  - SCIENTIFIC PUBLICATION.

PMID- 16652471
TI  - NUTRITIONAL STUDIES ON FUSARIUM LINI.

PMID- 16652472
TI  - ADSORPTION AS A MEANS OF DETERMINING RELATIVE HARDINESS IN THE APPLE.

PMID- 16652473
TI  - A STUDY OF THE CLEARING OF ALCOHOLIC PLANT EXTRACTS.

PMID- 16652474
TI  - THE ADAPTATION OF CERTAIN COLORIMETRIC METHODS TO THE ESTIMATION OF NITRATES,
      PHOSPHATES AND POTASSIUM IN PLANT SOLUTIONS.

PMID- 16652475
TI  - SOME FURTHER NOTES ON THE HYDROLYSIS OF STARCH GRAINS UNDER POLARIZED LIGHT.

PMID- 16652476
TI  - A CONDUCTIVITY CELL FOR CONTINUOUS MEASUREMENTS OF RESPIRATORY RATE.

PMID- 16652477
TI  - CITATION OF LITERATURE.

PMID- 16652478
TI  - NOTES.

PMID- 16652480
TI  - THE MECHANISM OF ACCUMULATION OF DYES BY LIVING CELLS.

PMID- 16652479
TI  - STUDIES ON THE OXYGEN-SUPPLYING POWER OF THE SOIL TOGETHER WITH QUANTITATIVE
      OBSERVATIONS ON THE OXYGEN-SUPPLYING POWER REQUISITE FOR SEED GERMINATION.

PMID- 16652481
TI  - EVIDENCE ON THE INDISPENSABLE NATURE OF ZINC AND BORON FOR HIGHER GREEN PLANTS.

PMID- 16652482
TI  - SOME CHEMICAL CHANGES INCIDENT TO RIPENING AND STORAGE IN THE GRIMES APPLE.

PMID- 16652483
TI  - GROWTH STUDIES ON FRUITS.

PMID- 16652484
TI  - PLANT GROWTH-PROMOTING SUBSTANCES, HYDROGEN ION CONCENTRATION AND THE
      REPRODUCTION OF LEMNA.

PMID- 16652485
TI  - DIFFERENCES IN RESISTANCE TO LOW TEMPERATURES SHOWN BY CLOVER VARIETIES.

PMID- 16652486
TI  - FOOD STORAGE.

PMID- 16652487
TI  - NOTES.

PMID- 16652488
TI  - TEMPERATURE EFFECTS IN THE METABOLISM OF WHEAT.

PMID- 16652489
TI  - SULPHUR METABOLISM OF YEAST.

PMID- 16652490
TI  - STUDIES ON THE OXIDATION OF CERTAIN FATTY ACIDS.

PMID- 16652491
TI  - THE DISTRIBUTION OF THE ROOTS OF SUGAR CANE IN THE SOIL IN THE HAWAIIAN ISLANDS.

PMID- 16652492
TI  - THE DIGESTION OF PECTIN AND METHYLATED GLUCOSES BY VARIOUS ORGANISMS.

PMID- 16652493
TI  - GROWTH OF YOUNG WHEAT PLANTS IN AUTO-IRRIGATED SOILS, AS RELATED TO THE WATER
      SUPPLYING POWER OF THE SOIL AND TO THE ADJUSTMENT OF THE AUTO-IRRIGATOR.

PMID- 16652494
TI  - THE CHEMICAL ANALYSIS OF PLANT TISSUES.

PMID- 16652495
TI  - THE USE OF POTASSIUM OXALATE AS A DELEADING REAGENT.

PMID- 16652496
TI  - AQUEOUS EXTRACTS OF SEEDS AS AGENTS IN THE PREPARATION OF SILVER SOLS.

PMID- 16652498
TI  - A DEVICE FOR MAINTAINING CONSTANT LEVEL OF CULTURE SOLUTIONS.

PMID- 16652497
TI  - CLIMATIC EFFECTS IN THE METABOLISM OF MAIZE.

PMID- 16652499
TI  - NOTES.

PMID- 16652501
TI  - NEGATIVE RESULTS ON PHYSIOLOGICAL BALANCE IN SOIL CULTURES.

PMID- 16652500
TI  - PLANT PHYSIOLOGY AT THE ITHACA CONGRESS.

PMID- 16652502
TI  - A LABORATORY METHOD OF PREPARING STARCH FROM MAIZE SEED.

PMID- 16652504
TI  - NOTES.

PMID- 16652503
TI  - THE ACTION OF ETHYLENE IN ACCELERATING THE BLANCHING OF CELERY.

PMID- 16652505
TI  - ON THE PASSAGE OF BORIC ACID AND CERTAIN SALTS INTO FRUITS AND VEGETABLES.

PMID- 16652506
TI  - NITROGENOUS METABOLISM OF PYRUS MALUS L.: I. INFLUENCE OF TEMPERATURE OF
      DESICCATION ON WATER-SOLUBLE NITROGENOUS CONSTITUENTS AND SEPARATION OF WATER
      SOLUBLE PROTEIN FROM NON-PROTEIN CONSTITUENTS.

PMID- 16652507
TI  - NITROGENOUS METABOLISM OF PYRUS MALUS L.: II. THE DISTRIBUTION OF NITROGEN IN THE
      INSOLUBLE CYTOPLASMIC PROTEINS.

PMID- 16652508
TI  - SOIL-MOISTURE CONDITIONS IN RELATION TO PLANT GROWTH.

PMID- 16652509
TI  - DOES THE PEA PLANT FIX ATMOSPHERIC NITROGEN?

PMID- 16652511
TI  - APPARATUS FOR CONTINUOUS DIALYSIS AT LOW TEMPERATURE.

PMID- 16652510
TI  - THE DETERMINATION OF POLYSACCHARIDES.

PMID- 16652512
TI  - NITROGENOUS METABOLISM OF PYRUS MALUS L.: III THE PARTITION OF NITROGEN IN THE
      LEAVES, ONE AND TWO YEAR BRANCH GROWTH AND NON-BEARING SPURS THROUGHOUT A YEAR'S
      CYCLE.

PMID- 16652513
TI  - THE CURRENT MINERAL NUTRIENT CONTENT OF THE PLANT SOLUTION AS AN INDEX OF
      METABOLIC LIMITING CONDITIONS.

PMID- 16652514
TI  - GROWTH STUDIES ON FRUITS AN EXPLANATION OF THE SHAPE OF THE GROWTH CURVE.

PMID- 16652515
TI  - CHEMICAL CHANGES ACCOMPANYING THE WESTERN YELLOW BLIGHT OF TOMATO.

PMID- 16652516
TI  - THE EFFECT OF ULTRAVIOLET RADIATION UPON YEAST CULTURE MEDIA.

PMID- 16652517
TI  - SEMIPERMEABILITY OF SEED COVERINGS AND STIMULATION OF SEEDS.

PMID- 16652518
TI  - THE USE OF ETHYLENE, PROPYLENE, AND SIMILAR COMPOUNDS IN BREAKING THE REST PERIOD
      OF TUBERS, BULBS, CUTTINGS, AND SEEDS.

PMID- 16652519
TI  - THE DETERMINATION OF SOLUBLE CARBOHYDRATES.

PMID- 16652520
TI  - THE DETERMINATION OF NITROGEN IN RELATIVELY SIMPLE COMPOUNDS.

PMID- 16652521
TI  - AN APPARATUS FOR CONTROLLING THE FLOW OF NUTRIENT SOLUTIONS IN PLANT CULTURES.

PMID- 16652522
TI  - DEVICES FOR SOWING AND GROWING SPORES.

PMID- 16652524
TI  - NOTES.

PMID- 16652523
TI  - IONIZATION AND ABSORPTION ISOELECTRIC POINTS.

PMID- 16652525
TI  - CARBOHYDRATE TRANSFORMATIONS IN CARROTS DURING STORAGE.

PMID- 16652526
TI  - NITROGENOUS METABOLISM OF PYRUS MALUS L.: IV. THE EFFECT OF SODIUM NITRATE
      APPLICATIONS ON THE TOTAL NITROGEN AND ITS PARTITION PRODUCTS IN THE LEAVES, NEW
      AND ONE YEAR BRANCH GROWTH THROUGHOUT A YEAR'S CYCLE.

PMID- 16652527
TI  - RELATION OF COMPOSITION TO GROWTH AND FRUITFULNESS OF YOUNG APPLE TREES AS
      AFFECTED BY GIRDLING, SHADING, AND PHOTOPERIOD.

PMID- 16652528
TI  - TEMPERATURE AND OTHER FACTORS AFFECTING THE REST PERIOD OF POTATO TUBERS.

PMID- 16652529
TI  - THE BASIC NITROGEN OF PLANT EXTRACTS.

PMID- 16652530
TI  - ELECTRODIALYSIS AS A MEANS OF STUDYING BIOCHEMICAL DIFFERENCES IN ABNORMAL APPLE
      TISSUE.

PMID- 16652531
TI  - GERMINATION AND GROWTH OF SEEDS AS DEPENDENT UPON SELECTIVE IRRADIATION.

PMID- 16652532
TI  - LENGTH OF LIFE OF SEED-PIECE ROOTS OF SUGAR CANE AND PROGRESS OF THE ROOTS IN THE
      SOIL AT DIFFERENT AGES OF GROWTH.

PMID- 16652533
TI  - FACTORS AFFECTING THE COMPOSITION OF DATES.

PMID- 16652534
TI  - THE EFFECT OF ETHYLENE ON THE RESPIRATION OF BANANAS DURING RIPENING.

PMID- 16652535
TI  - NOTES.

PMID- 16652536
TI  - THE FIRST INTERNATIONAL CONGRESS OF SOIL SCIENCE.

PMID- 16652537
TI  - THE MEASUREMENT AND INTERPRETATION OF THE WATER-SUPPLYING POWER OF THE SOIL WITH
      SPECIAL REFERENCE TO LAWN GRASSES AND SOME OTHER PLANTS.

PMID- 16652538
TI  - DIFFERENTIAL STAINING OF SPECIALIZED CELLS IN BEGONIA WITH INDICATORS.

PMID- 16652539
TI  - A MODIFIED KJELDAHL METHOD FOR THE DETERMINATION OF THE NITROGEN CONTENT OF
      YEAST.

PMID- 16652540
TI  - THE INFLUENCE OF DIRECT IRRADIATION BY A QUARTZ MERCURY ARC LAMP UPON THE
      GERMINATION AND GROWTH OF CERTAIN SEEDS.

PMID- 16652541
TI  - THE EFFECT OF BORIC ACID ON THE GROWTH OF TOBACCO PLANTS IN NUTRIENT SOLUTIONS.

PMID- 16652542
TI  - NOTES ON APPARATUS FOR LOW TEMPERATURE RESPIRATION STUDIES.

PMID- 16652543
TI  - THE DETERMINATION OF PEPTIDE AND BASIC FORMS OF NITROGEN.

PMID- 16652544
TI  - THE APPLICATION OF PHYSIOLOGICAL METHODS TO WEED CONTROL.

PMID- 16652545
TI  - A MODIFIED VAN TIEGHEM CELL FOR PHYSIOLOGICAL STUDIES OF POLLEN GERMINATION.

PMID- 16652546
TI  - NOTES.

PMID- 16652547
TI  - STUDIES UPON WHEAT GROWN UNDER CONSTANT CONDITIONS-I.

PMID- 16652548
TI  - NITROGEN METABOLISM IN THE SOY BEAN.

PMID- 16652550
TI  - ON THE NITROGEN CONTENT OF GROWING CULTURES OF MYCODERMA AND OF SACCHAROMYCES
      CEREVISIAE.

PMID- 16652549
TI  - THE EFFECT OF ACCUMULATED CARBON DIOXIDE ON PLANT RESPIRATION.

PMID- 16652551
TI  - STUDIES UPON WHEAT GROWN UNDER CONSTANT CONDITIONS-II.

PMID- 16652552
TI  - THE DEVELOPMENT OF CHLOROPHYLL IN SEEDLINGS IN DIFFERENT RANGES OF WAVE LENGTHS
      OF LIGHT.

PMID- 16652553
TI  - SIMILARITY BETWEEN PHYSICOCHEMICAL AND BIOLOGICAL REACTIONS.

PMID- 16652554
TI  - PHOTOSYNTHESIS IN ABSENCE OF OXYGEN.

PMID- 16652555
TI  - A STUDY OF THE EFFECT OF H-ION CONCENTRATION ON THE GROWTH OF AGARICUS
      CAMPESTRIS.

PMID- 16652557
TI  - NOTES.

PMID- 16652556
TI  - EFFECT OF HIGH TEMPERATURE ON CHARACTER OF GROWTH OF CABBAGE.

PMID- 16652558
TI  - STUDIES IN PERIODIC PRECIPITATION.

PMID- 16652559
TI  - CHANGES IN THE BUFFER SYSTEM OF THE WHEAT PLANT DURING ITS DEVELOPMENT.

PMID- 16652560
TI  - LIPIDES AND THEIR ESTIMATION IN VEGETABLE TISSUES.

PMID- 16652561
TI  - A STUDY OF CERTAIN CONSTITUENTS OF THE LEAF AND THEIR RELATION TO THE BURNING
      QUALITIES OF TOBACCO.

PMID- 16652562
TI  - MUCK-SOIL REACTION AS RELATED TO THE GROWTH OF CERTAIN LEAF VEGETABLES.

PMID- 16652563
TI  - THE EXTRACTION AND SEPARATION OF CHLOROPHYLL (alpha+beta) CAROTIN AND XANTHOPHYLL
      IN FRESH GREEN LEAVES, PRELIMINARY TO THEIR QUANTITATIVE DETERMINATION.

PMID- 16652564
TI  - FURTHER EVIDENCE OF THE ESSENTIAL NATURE OF ZINC FOR THE GROWTH OF HIGHER GREEN
      PLANTS.

PMID- 16652565
TI  - A STERILE CHARACTER IN SOYBEANS.

PMID- 16652567
TI  - NOTES.

PMID- 16652566
TI  - TIMIRIAZEFF AND THE TIMIRIAZEFF AGRICULTURAL INSTITUTE.

PMID- 16652568
TI  - EFFECTS OF THE ABSENCE OF BORON AND OF SOME OTHER ESSENTIAL ELEMENTS ON THE CELL
      AND TISSUE STRUCTURE OF THE ROOT TIPS OF PISUM SATIVUM.

PMID- 16652569
TI  - CALCIUM, POTASSIUM, AND IRON BALANCE IN CERTAIN CROP PLANTS IN RELATION TO THEIR
      METABOLISM.

PMID- 16652570
TI  - AN APPARATUS FOR THE GROWTH OF PLANTS IN A CONTROLLED ENVIRONMENT.

PMID- 16652571
TI  - ALUMINUM TOXICITY.

PMID- 16652572
TI  - SOME STUDIES ON THE HARDINESS OF CERTAIN SPECIES OF VACCINIUM.

PMID- 16652573
TI  - CERTAIN PHYSICOCHEMICAL PROPERTIES OF PINEAPPLE STEM COLLOIDS.

PMID- 16652574
TI  - THE QUANTITATIVE DETERMINATION OF CHLOROPHYLL.

PMID- 16652575
TI  - BIOCHEMICAL STUDIES ON SEED VIABILITY: I. MEASUREMENTS OF CONDUCTANCE AND
      REDUCTION.

PMID- 16652576
TI  - PLANT PHYSIOLOGY IN RUSSIA.

PMID- 16652578
TI  - NOTES.

PMID- 16652577
TI  - SOIL MOISTURE AT PERMANENT WILTING OF PLANTS.

PMID- 16652579
TI  - GERMINATIVE ENERGY OF LOTS OF CONIFEROUS-TREE SEED, AS RELATED TO INCUBATION
      TEMPERATURE AND TO DURATION OF INCUBATION.

PMID- 16652580
TI  - OSMOTIC PRESSURE, OSMOTIC VALUE, AND SUCTION TENSION.

PMID- 16652581
TI  - PLANT NUTRITION STUDIES IN RELATION TO THE TRIANGULAR SYSTEM OF WATER CULTURES.

PMID- 16652582
TI  - ANATOMICAL MATERIAL FOR THE STUDY OF GROWTH DIFFERENTIATION IN HIGHER PLANTS.

PMID- 16652583
TI  - THE INFLUENCE OF ONE ION ON THE ACCUMULATION OF ANOTHER BY PLANT CELLS WITH
      SPECIAL REFERENCE TO EXPERIMENTS WITH NITELLA.

PMID- 16652584
TI  - THE PREPARATION OF CHLOROPHYLL.

PMID- 16652585
TI  - A METHOD FOR THE DETERMINATION OF INORGANIC NITROGEN IN PLANT EXTRACTS.

PMID- 16652587
TI  - TWO PLANT MATERIAL DRIERS.

PMID- 16652586
TI  - EFFECT OF SUNSHINE AND SHAPE OF FRUIT ON THE RATE OF RIPENING OF TOMATO FRUITS.

PMID- 16652588
TI  - NOTES.

PMID- 16652589
TI  - STUDIES IN EXPERIMENTAL CYTOLOGY.

PMID- 16652590
TI  - SOME CRITICAL COMMENTS ON THE METHODS EMPLOYED IN THE EXPRESSION OF LEAF SAPS.

PMID- 16652591
TI  - CHEMICAL RELATIONSHIP BETWEEN SCION AND STOCK IN CITRUS.

PMID- 16652592
TI  - STORAGE OF TRUCK CROPS: THE GIRASOLE, HELIANTHUS TUBEROSUS.

PMID- 16652593
TI  - SEASONAL VARIATION OF THE CHLOROPLAST PIGMENTS IN SEVERAL PLANTS ON THE MALL AT
      WASHINGTON, D. C.

PMID- 16652595
TI  - X-RAY PHOTOGRAPHY OF MINERAL ACCUMULATIONS IN PLANTS.

PMID- 16652594
TI  - EFFECTS OF STORAGE ON ALCOHOLIC EXTRACTS OF PLANT TISSUES. AMINO ACID CHANGES.

PMID- 16652596
TI  - JULIUS VON SACHS.

PMID- 16652598
TI  - SCHLOESING'S EXPERIMENTS ON THE RELATION OF TRANSPIRATION TO THE TRANSLOCATION OF
      MINERALS.

PMID- 16652597
TI  - AN INVADING POTATO SPROUT.

PMID- 16652599
TI  - NOTES.

PMID- 16652600
TI  - THE INFLUENCE OF BORON ON THE CHEMICAL COMPOSITION AND GROWTH OF THE TOMATO
      PLANT.

PMID- 16652602
TI  - THE MECHANISM OF THE WATER TIGHT DOOR OF THE UTRICULARIA TRAP.

PMID- 16652601
TI  - RELATION BETWEEN TOP AND ROOT SIZE IN HERBACEOUS PLANTS.

PMID- 16652603
TI  - A STUDY OF THE RELATIONS BETWEEN CHLOROPLAST PIGMENTS AND DRY WEIGHTS OF TOPS IN
      DENT CORN.

PMID- 16652604
TI  - THE TOXIC SUBSTANCE PRODUCED BY THE EYE-SPOT FUNGUS OF SUGAR CANE,
      HELMINTHOSPORIUM SACCHARI BUTLER.

PMID- 16652605
TI  - THE ABSORPTION OF PHOSPHATE FROM SOIL AND SOLUTION CULTURES.

PMID- 16652606
TI  - THE EXTRACTION OF NITROGENOUS MATERIALS FROM PEAR TISSUES.

PMID- 16652607
TI  - HEMICELLULOSE AS A STORAGE CARBOHYDRATE IN WOODY PLANTS, WITH SPECIAL REFERENCE
      TO THE APPLE.

PMID- 16652608
TI  - IDENTIFICATION OF CERTAIN SPECIES OF CITRUS BY COLORIMETRIC TESTS.

PMID- 16652610
TI  - THE EFFECT OF TEMPERATURE ON FLOWERS.

PMID- 16652609
TI  - THE EFFECT OF POTASSIUM, NITROGEN AND PHOSPHORUS FERTILIZING UPON THE CHLOROPLAST
      PIGMENTS, UPON THE MINERAL CONTENT OF THE LEAVES, AND UPON PRODUCTION IN CROP
      PLANTS.

PMID- 16652611
TI  - WILHELM PFEFFER.

PMID- 16652613
TI  - NOTES.

PMID- 16652612
TI  - A SIMPLE METHOD FOR NITRATE NITROGEN DETERMINATION IN WHEAT PLANTS.

PMID- 16652614
TI  - ON SOME LIMITING FACTORS IN THE USE OF SATURATED PETROLEUM OILS AS INSECTICIDES.

PMID- 16652615
TI  - OPENING OF STOMATA IN DIFFERENT RANGES OF WAVE LENGTHS OF LIGHT.

PMID- 16652616
TI  - MECHANISM OF CELL WALL FORMATION.

PMID- 16652617
TI  - THE PURE PIGMENTS, CAROTIN AND XANTHOPHYLL, AND THE TSWETT ADSORPTION METHOD.

PMID- 16652618
TI  - GROWTH STUDIES ON FRUITS. RESPIRATION OF TOMATO FRUITS.

PMID- 16652619
TI  - SOME OBSERVATIONS ON THE MICROCHEMICAL DEMONSTRATION OF PHLORIDZIN.

PMID- 16652620
TI  - THE EFFECT OF pH VALUE AND HYDROGEN PEROXIDE CONCENTRATION ON FRUIT OXIDASE
      ACTIVITY.

PMID- 16652621
TI  - TESTING THE SUGAR CONTENT OF BEETS FOR GENETICAL PURPOSES.

PMID- 16652622
TI  - EFFECT OF ACID AND ALKALINE HYDROLYSIS ON THE ESTIMATION OF HEMICELLULOSE AND
      ASSOCIATED GROUPS IN YOUNG APPLE WOOD.

PMID- 16652623
TI  - INFLUENCE OF SHAPE ON THE CHEMICAL COMPOSITION OF POTATO TUBERS.

PMID- 16652624
TI  - THE WATER CONTENT OF WHEAT LEAVES AT FLOWERING TIME.

PMID- 16652625
TI  - NOTES.

PMID- 16652626
TI  - COMPOSITION AND GROWTH INITIATION OF DORMANT BARTLETT PEAR SHOOTS AS INFLUENCED
      BY TEMPERATURE.

PMID- 16652627
TI  - RELATION BETWEEN THE DEVELOPMENT OF ROOT SYSTEM AND SHOOT UNDER LONG- AND SHORT
      DAY ILLUMINATION.

PMID- 16652628
TI  - SOME SEASONAL CHANGES IN THE TRACHEAL SAP OF PEAR AND APRICOT TREES.

PMID- 16652629
TI  - PHYSICAL MEASUREMENTS OF THE WINTER WHEAT PLANT AT VARIOUS STAGES IN ITS
      DEVELOPMENT.

PMID- 16652630
TI  - SOME EFFECTS OF CALCIUM DEFICIENCY ON PISUM SATIVUM.

PMID- 16652631
TI  - THE INSOLUBLE TYROSINASE OF THE VELVET BEAN SEED COAT.

PMID- 16652632
TI  - THE DETERMINATION OF NITRATE IN GREEN TOMATO AND LETTUCE TISSUES.

PMID- 16652633
TI  - MOISTURE FLUCTUATIONS IN EXTRACTED PLANT SOLUTIONS AND IN LEAF TISSUE.

PMID- 16652634
TI  - THE EFFECT OF pH VALUE ON THE INACTIVATION TEMPERATURE OF FRUIT OXIDASE.

PMID- 16652636
TI  - NOTES.

PMID- 16652635
TI  - JOANNES BAPTISTA VAN HELMONT.

PMID- 16652637
TI  - THE RELATION OF TEMPERATURE AND THE PARTIAL PRESSURE OF OXYGEN TO RESPIRATION AND
      GROWTH IN GERMINATING WHEAT.

PMID- 16652638
TI  - EXPERIMENTS WITH TRIANEA ON ANTAGONISM AND ABSORPTION.

PMID- 16652639
TI  - ENERGY EMANATION DURING CELL DIVISION PROCESSES (M-RAYS).

PMID- 16652640
TI  - TOXICITY OF SOME ALIPHATIC ALCOHOLS.

PMID- 16652641
TI  - CHANGES IN THE COMPOSITION OF THE TOMATO PLANT ACCOMPANYING DIFFERENT STAGES OF
      YELLOWS.

PMID- 16652642
TI  - THE FOURTH PACIFIC SCIENCE CONGRESS.

PMID- 16652644
TI  - NOTE ON THE RELATION OF RATE OF RESPIRATION TO CHEMICAL COMPOSITION IN FRESH
      VEGETABLES.

PMID- 16652643
TI  - HUGO DE VRIES.

PMID- 16652645
TI  - THE PHYSIOLOGICAL LABORATORY OF THE BOTANICAL INSTITUTE IN THE UNIVERSITY OF
      ZAGREB.

PMID- 16652646
TI  - NOTES.

PMID- 16652647
TI  - RELATION OF INCREASED WATER CONTENT AND DECREASED AERATION TO ROOT DEVELOPMENT IN
      HYDROPHYTES.

PMID- 16652648
TI  - A FURFURAL-YIELDING SUBSTANCE AS A SPLITTING PRODUCT OF PROTOPECTIN DURING THE
      RIPENING OF FRUITS.

PMID- 16652649
TI  - ASH CONSTITUENTS OF PASTURE GRASSES, THEIR STANDARD ELECTRODE POTENTIALS AND
      ECOLOGICAL SIGNIFICANCE.

PMID- 16652651
TI  - DORMANCY AND GROWTH STUDIES OF THE AMERICAN LOTUS, NELUMBO LUTEA.

PMID- 16652650
TI  - PRELIMINARY RESULTS IN MEASURING THE HARDINESS OF PLANTS.

PMID- 16652652
TI  - TENTATIVE CLASSIFICATION OF SYMPTOMATIC TYPES OF "TOMATO POCKETS".

PMID- 16652653
TI  - THE ROLE OF MANGANESE IN THE NUTRITION OF LEMNA.

PMID- 16652654
TI  - A MICROELECTRODE FOR THE RAPID DETERMINATION OF THE HYDRION CONCENTRATION OF
      EXPRESSED JUICES FROM SMALL AMOUNTS OF PLANT TISSUE.

PMID- 16652655
TI  - METHODS FOR THE QUANTITATIVE EXTRACTION AND SEPARATION OF THE PLASTID PIGMENTS OF
      TOBACCO.

PMID- 16652657
TI  - A CASE OF SECOND CROP SEEDLESS APPLES.

PMID- 16652656
TI  - SOME GROWTH CURVES OF BARLEY KERNELS.

PMID- 16652658
TI  - THE MASS FACTOR IN THE ENERGY RELATIONS OF LEAVES.

PMID- 16652660
TI  - NOTES.

PMID- 16652659
TI  - JAN INGEN-HOUSZ.

PMID- 16652661
TI  - EFFECTS OF INSOLATION AND SOIL CHARACTERISTICS ON TISSUE FLUID REACTION IN WHEAT.

PMID- 16652662
TI  - TITRATION CURVES OF ETIOLATED AND OF GREEN WHEAT SEEDLINGS REPRODUCED WITH BUFFER
      MIXTURES.

PMID- 16652663
TI  - THE PHYSIOLOGY OF CONVOLVULUS ARVENSIS (MORNING-GLORY OR BINDWEED) IN RELATION TO
      ITS CONTROL BY CHEMICAL SPRAYS.

PMID- 16652664
TI  - DETERMINATION OF THE PERCENTAGE OF SUCROSE IN SUGAR BEETS FOR RESEARCH PURPOSES.

PMID- 16652665
TI  - ESTIMATION OF NITRATE NITROGEN IN PLANT JUICE: A STUDY OF THE EXPRESSION AND
      CLARIFICATION OF THE JUICE.

PMID- 16652666
TI  - THE EFFECT OF FERTILIZER ON THE QUALITY AND KEEPING QUALITY OF WATERMELONS.

PMID- 16652668
TI  - ACCUMULATED IRON IN THE NODES OF CORN PLANTS.

PMID- 16652667
TI  - THE ESSENTIAL NATURE OF BORON TO THE GROWTH AND FRUITING OF THE TOMATO.

PMID- 16652669
TI  - THE CHEMICAL CHANGES IN PEAS AFTER PICKING.

PMID- 16652670
TI  - A METHOD FOR THE RAPID DETERMINATION OF PHOSPHATE IN FRESH PLANT TISSUES.

PMID- 16652671
TI  - THE ASKENASY DEMONSTRATION.

PMID- 16652672
TI  - NICOLAS THEODORE DE SAUSSURE.

PMID- 16652673
TI  - SOME ACCESSORIES FOR THE DISSECTING MICROSCOPE.

PMID- 16652675
TI  - NOTES.

PMID- 16652674
TI  - EFFECT OF SOMATIC INJURY UPON YIELD IN CORN.

PMID- 16652677
TI  - ELECTRIC CORRELATION POTENTIALS IN THE LEAF OF BRYOPHYLLUM.

PMID- 16652676
TI  - THE FEEDING POWER OF PLANTS.

PMID- 16652678
TI  - RESPIRATION OF APPLE TWIGS IN RELATION TO WINTER HARDINESS.

PMID- 16652679
TI  - CARBON DIOXIDE DISSOLVED IN PLANT SAP AND ITS EFFECT ON RESPIRATION MEASUREMENTS.

PMID- 16652680
TI  - INFLUENCE OF LEAFAGE REMOVAL ON ANATOMICAL STRUCTURE OF ROOTS OF STIPA PULCHRA
      AND BROMUS HORDEACEUS.

PMID- 16652681
TI  - DISTRIBUTION OF MOISTURE, DRY MATTER, AND SUGARS IN THE MATURING CORN STEM.

PMID- 16652683
TI  - CALLUSING OF COTTON STEM CUTTINGS.

PMID- 16652682
TI  - EFFECT OF MOLDS ON TEMPERATURE OF STORED GRAIN.

PMID- 16652684
TI  - PRELIMINARY STUDY OF ELONGATION OF ROOTS OF GEORGIA COLLARDS AS AFFECTED BY
      SODIUM LUMINAL.

PMID- 16652685
TI  - EFFECT OF VARIOUS METHODS OF STORAGE ON THE CHLOROPHYLL CONTENT OF LEAVES.

PMID- 16652687
TI  - WILHELM HOFMEISTER.

PMID- 16652686
TI  - EFFECT OF FERTILITY ON THE CARBOHYDRATE-NITROGEN RELATION IN THE SOYBEAN.

PMID- 16652688
TI  - USEFUL DEVICE FOR EVAPORATING ALCOHOL FROM PLANT EXTRACTS.

PMID- 16652689
TI  - NOTES.

PMID- 16652690
TI  - MOVEMENT OF ORGANIC MATERIALS IN PLANTS.

PMID- 16652691
TI  - RELATION OF H-ION CONCENTRATION OF TISSUE FLUIDS TO THE DISTRIBUTION OF IRON IN
      PLANTS.

PMID- 16652692
TI  - PHENOLASE ACTIVITY IN RELATION TO SEED VIABILITY.

PMID- 16652693
TI  - USE OF EXPRESSED SAP IN PHYSIOLOGIC STUDIES OF CORN.

PMID- 16652694
TI  - EFFECT OF PETROLEUM OILS ON THE RESPIRATION OF BEAN LEAVES.

PMID- 16652695
TI  - STRANGULATION OF COTTON ROOTS.

PMID- 16652696
TI  - TESTS OF CHIBNALL'S METHOD OF EXTRACTION FOR INVESTIGATING WINTER HARDINESS OF
      PLANTS.

PMID- 16652697
TI  - COMPOSITION AND QUALITY OF PENNSYLVANIA CIGAR-LEAF TOBACCO AS RELATED TO
      FERTILIZER TREATMENT.

PMID- 16652698
TI  - A STUDY OF THE AMMONIA CONTENT OF CIGAR SMOKE.

PMID- 16652699
TI  - JEAN SENEBIER.

PMID- 16652700
TI  - GRAFTING EXPERIMENTS WITH COTTON.

PMID- 16652701
TI  - TEMPERATURE AS A POSSIBLE FACTOR IN REGENERATION.

PMID- 16652702
TI  - NOTES.

PMID- 16652704
TI  - SOME REACTIONS OF THE BANANA TO PRESSURE, GRAVITY, AND DARKNESS.

PMID- 16652703
TI  - FOOD RESERVES IN RELATION TO OTHER FACTORS LIMITING THE GROWTH OF GRASSES.

PMID- 16652705
TI  - AN EXPERIMENTAL STUDY OF THE GERMINATION OF WHEAT SEED UNDER WATER, AS RELATED TO
      TEMPERATURE AND AERATION.

PMID- 16652706
TI  - DISCHARGE OF SACCHARASE FROM MYCELIUM OF PENICILLIUM GLAUCUM.

PMID- 16652707
TI  - LIGHT AND THE CAROTINOID CONTENT OF CERTAIN FRUITS AND VEGETABLES.

PMID- 16652708
TI  - STUDIES ON INANITION IN ARACHIS AND PHASEOLUS.

PMID- 16652709
TI  - COMPARISON OF THE CHEMICAL COMPOSITION OF SOME MARINE ALGAE.

PMID- 16652710
TI  - RELATION OF PHOTOTROPISM TO THE WAVE-LENGTH OF LIGHT.

PMID- 16652711
TI  - VARIATIONS IN THE O(g) OF PLANT TISSUES.

PMID- 16652712
TI  - FACTORS MODIFYING THE TOXICITY OF PHENOL.

PMID- 16652713
TI  - STATISTICAL STUDY OF THE TOTAL NITROGEN IN BARTLETT PEAR SHOOTS.

PMID- 16652714
TI  - COPPER AS AN ESSENTIAL FOR PLANT GROWTH.

PMID- 16652715
TI  - RELATION OF CATALASE ACTIVITY TO PHYSIOLOGICAL BREAKDOWN IN JONATHAN APPLES.

PMID- 16652716
TI  - IS ELECTRODIALYSIS USEFUL IN A STUDY OF APPLE TISSUE.

PMID- 16652717
TI  - CHANGES IN OSMOTIC PRESSURE OF BANANAS DURING RIPENING.

PMID- 16652719
TI  - NOTES.

PMID- 16652718
TI  - A QUANTITATIVE DEMONSTRATION OF OSMOTIC EQUILIBRIUM.

PMID- 16652720
TI  - ABSORPTION OF MINERAL ELEMENTS BY PLANTS IN RELATION TO SOIL PROBLEMS.

PMID- 16652721
TI  - INFLUENCE OF ACETIC, PROPIONIC, NORMAL BUTYRIC AND SULPHURIC ACIDS AND POTASSIUM
      ACETATE ON ELONGATION OF PRIMARY ROOTS OF SEEDLINGS OF WHITE LUPINE.

PMID- 16652723
TI  - SOME EFFECTS OF ACETYLENE ON THE RIPENING PROCESSES OF BANANAS.

PMID- 16652722
TI  - LIGHT SOURCES AND LIGHT MEASUREMENTS.

PMID- 16652724
TI  - WATER-SUPPLYING POWER OF THE SOIL UNDER DIFFERENT SPECIES OF GRASS AND WITH
      DIFFERENT RATES OF WATER APPLICATION.

PMID- 16652725
TI  - MOVEMENT OF WATER IN PLANTS AS AFFECTED BY A MUTUAL RELATION BETWEEN THE
      HYDROSTATIC AND PNEUMATIC SYSTEMS.

PMID- 16652726
TI  - EXTERNAL POLARITY POTENTIALS IN THE APEX OF THE DOUGLAS FIR BEFORE AND AFTER
      MECHANICAL STIMULATION.

PMID- 16652727
TI  - SEASONAL CHANGES IN TOTAL, SOLUBLE, SOLUBLE-PROTEIN, NON-PROTEIN, AND INSOLUBLE
      NITROGEN IN CURRENT YEAR'S SHOOTS OF BARTLETT PEAR.

PMID- 16652728
TI  - STUDIES ON PARENCHYMATOUS AND VASCULAR PLANT TISSUES, SOME ANALYTICAL AND
      SPECIFIC GRAVITY DATA.

PMID- 16652729
TI  - PERMEABILITY OF THE SKIN OF APPLES AS MEASURED BY EVAPORATION LOSS.

PMID- 16652730
TI  - RESPIRATION STUDIES OF STRAWBERRIES.

PMID- 16652731
TI  - EFFECT OF MANGANESE, COPPER AND ZINC ON THE GROWTH OF YEAST.

PMID- 16652732
TI  - INFLUENCE OF DRY SOIL ON ROOT EXTENSION.

PMID- 16652733
TI  - COMPARISON OF METHODS OF DETERMINING MOISTURE IN CORN TISSUES.

PMID- 16652734
TI  - EFFECTS OF HIGH SOIL MOISTURE AND LACK OF SOIL AERATION UPON FRUITING BEHAVIOR OF
      YOUNG COTTON PLANTS.

PMID- 16652736
TI  - NOTES.

PMID- 16652735
TI  - PROOF OF THE ESSENTIAL NATURE OF COPPER FOR HIGHER GREEN PLANTS.

PMID- 16652737
TI  - EFFECTS OF CALCIUM DEFICIENCY ON NITRATE ABSORPTION AND ON METABOLISM IN TOMATO.

PMID- 16652738
TI  - ELECTRIC CORRELATION BETWEEN LIVING CELLS IN CORTEX AND WOOD IN THE DOUGLAS FIR.

PMID- 16652739
TI  - NOTES ON THE NUTRIENT REQUIREMENTS AND THE HISTOLOGY OF THE CRANBERRY (VACCINIUM
      MACROCARPON AIT.) WITH SPECIAL REFERENCE TO MYCORRHIZA.

PMID- 16652740
TI  - EFFECT OF CUTTING AND FERTILIZER APPLICATIONS ON GRASS DEVELOPMENT.

PMID- 16652741
TI  - EFFECT OF X-IRRADIATION UPON GROWTH AND REPRODUCTION OF TOMATO.

PMID- 16652742
TI  - EFFECT OF FERTILIZERS AND DATE OF PLANTING ON THE PHYSIOLOGICAL DEVELOPMENT OF
      THE CORN PLANT.

PMID- 16652743
TI  - COMPARISON OF TWO METHODS OF MEASURING STOMATAL APERTURE.

PMID- 16652744
TI  - MECHANISM OF ROOT-CONTRACTION IN BRODIAEA LACTEA.

PMID- 16652746
TI  - OBSERVATIONS ON THE RED COLOR OF THE BLOOD ORANGE.

PMID- 16652745
TI  - THE SENSITIVITY OF RED CLOVER (TRIFOLIUM PRATENSE) TO SMALL AMOUNTS OF BORON AND
      MANGANESE.

PMID- 16652747
TI  - NOTES.

PMID- 16652748
TI  - WILTING AND WITHERING OF GRASSES IN GREENHOUSE CULTURES AS RELATED TO WATER
      SUPPLYING POWER OF THE SOIL.

PMID- 16652749
TI  - SEASONAL CHANGES IN THE COMPOSITION OF THE NON-PROTEIN NITROGEN IN THE CURRENT
      YEAR'S SHOOTS OF BARTLETT PEAR.

PMID- 16652750
TI  - CHEMICAL EQUIVALENT BASE EXCHANGE REACTIONS IN PLANTS.

PMID- 16652751
TI  - RAPIDITY OF RESPONSE OF SPINACH TO CHANGE IN PHOTOPERIOD.

PMID- 16652752
TI  - MODE OF OCCURRENCE OF CAOUTCHOUC IN THE GUAYULE, PARTHENIUM ARGENTATUM GRAY, AND
      ITS FUNCTION.

PMID- 16652753
TI  - OXYGEN CONSUMPTION AND CARBON DIOXIDE PRODUCTION DURING THE GROWTH OF YEAST.

PMID- 16652754
TI  - EFFECT OF HOT-WATER TREATMENT ON THE CARBOHYDRATE CHANGES IN NARCISSUS BULBS
      DURING STORAGE.

PMID- 16652755
TI  - CATALASE ACTIVITY IN TOMATO FRUITS AT DIFFERENT STAGES OF THEIR DEVELOPMENT.

PMID- 16652756
TI  - EFFECT OF BORON ON THE GROWTH OF LETTUCE.

PMID- 16652757
TI  - MOVEMENT OF ORGANIC MATERIALS IN PLANTS: A NOTE ON A RECENTLY SUGGESTED
      MECHANISM.

PMID- 16652758
TI  - CONTAINER FOR THE STUDY OF THE BEHAVIOR OF INDIVIDUAL ROOTS.

PMID- 16652759
TI  - A SIMPLE DILATOMETER.

PMID- 16652760
TI  - NOTES.

PMID- 16652761
TI  - AVAILABLE WATER AND THE WILTING OF PLANTS.

PMID- 16652762
TI  - METHODS OF DETERMINING GLUCOSE AND FRUCTOSE IN CORN TISSUES.

PMID- 16652763
TI  - INVESTIGATIONS OF THE HARDINESS OF PLANTS BY MEASUREMENT OF ELECTRICAL
      CONDUCTIVITY.

PMID- 16652764
TI  - GROWTH AND DEVELOPMENT AS INFLUENCED BY FRUIT AND SEED FORMATION.

PMID- 16652765
TI  - CHANGES ACCOMPANYING FRUIT DEVELOPMENT IN THE GARDEN PEA.

PMID- 16652766
TI  - FACTORS AFFECTING THE DISTRIBUTION OF IRON IN PLANTS.

PMID- 16652767
TI  - HYDROGEN-ION CONCENTRATION AND IRON CONTENT OF TRACHEAL SAP FROM GREEN AND
      CHLOROTIC PEAR TREES.

PMID- 16652768
TI  - USE OF EXPRESSED SAP IN DETERMINING THE COMPOSITION OF CORN TISSUE.

PMID- 16652769
TI  - CHANGES IN THE COMPOSITION OF THE GARDEN PEA AFTER HARVEST.

PMID- 16652770
TI  - SEASONAL SHRINKAGE OF MONTEREY PINE AND REDWOOD TREES.

PMID- 16652771
TI  - CONTROL OF THE FLUX EQUILIBRIUM OF ELECTROCHEMICAL PROCESSES AND ELECTRIC
      POLARITY IN THE DOUGLAS FIR BY TEMPERATURE.

PMID- 16652772
TI  - FLOWER PRODUCTION FROM GLADIOLUS CORMS HARVESTED AT DIFFERENT STAGES OF RIPENING.

PMID- 16652773
TI  - FIELD METHOD FOR ESTIMATING NITRATE, PHOSPHATE, AND POTASSIUM IN PLANTS.

PMID- 16652774
TI  - SEASONAL CHANGES IN THE COMPOSITION OF THE INSOLUBLE NITROGEN FRACTION IN THE
      CURRENT YEAR'S SHOOTS OF BARTLETT PEAR.

PMID- 16652776
TI  - SIERGEI PAVLOVITCH KOSTYTCHEV.

PMID- 16652775
TI  - CHLOROSIS OF TREES.

PMID- 16652777
TI  - SOME PHOTOPERIODIC AND TEMPERATURE RESPONSES OF THE RADISH.

PMID- 16652778
TI  - TOXICITY OF ROOT EXCRETIONS.

PMID- 16652779
TI  - NOTES.

PMID- 16652780
TI  - PHLOEM ANATOMY, EXUDATION, AND TRANSPORT OF ORGANIC NUTRIENTS IN CUCURBITS.

PMID- 16652781
TI  - COMPOSITION OF CURRENT AND PREVIOUS SEASON'S BRANCH GROWTH IN RELATION TO
      VEGETATIVE AND REPRODUCTIVE RESPONSES IN PYRUS MALUS L.

PMID- 16652782
TI  - RELATION OF AGE AND OF SEASONAL CONDITIONS TO COMPOSITION OF ROOT, PETIOLE, AND
      LEAF BLADE IN RHUBARB.

PMID- 16652783
TI  - MECHANISM OF THE ACTION OF LIGHT AND OTHER FACTORS ON STOMATAL MOVEMENT.

PMID- 16652784
TI  - COMPARISON OF THE EFFECTS OF TEMPERATURE ON THE RADIAL AND LONGITUDINAL ELECTRIC
      POLARITIES IN WOOD AND CORTEX OF THE DOUGLAS FIR.

PMID- 16652785
TI  - DETERMINATION OF THE INORGANIC NITROGEN IN THE CORN PLANT BY THE EXPRESSED SAP
      METHOD.

PMID- 16652786
TI  - RELATION OF HYDROGEN-ION CONCENTRATION OF SOILS TO THE GROWTH OF CERTAIN PASTURE
      PLANTS.

PMID- 16652787
TI  - ISOLATION IN PURE CULTURE OF GREEN ALGAE FROM SOIL BY A SIMPLE TECHNIQUE.

PMID- 16652788
TI  - SUGGESTIONS FOR GROWING MASS CULTURES OF ALGAE FOR VITAMIN AND OTHER
      PHYSIOLOGICAL STUDY.

PMID- 16652789
TI  - DETERMINATION OF STARCH IN PLANT TISSUES.

PMID- 16652790
TI  - MANNOSE AND THE FIRST SUGAR OF PHOTOSYNTHESIS.

PMID- 16652791
TI  - A PLANT TEST OF THE SUN LAMP.

PMID- 16652792
TI  - A DUAL-PURPOSE MICROSCOPE LAMP.

PMID- 16652793
TI  - A USEFUL INSTRUMENT FOR MEASURING HEIGHT GROWTH.

PMID- 16652794
TI  - NOTES.

PMID- 16652795
TI  - EFFECTS OF THE PHYSICAL ENVIRONMENT ON THE PHYSICO-CHEMICAL PROPERTIES OF PLANT
      SAPS, AND THE RELATION OF THESE PROPERTIES TO LEAF TEMPERATURE.

PMID- 16652796
TI  - EFFECTS OF SULPHUR DEFICIENCY ON METABOLISM IN TOMATO.

PMID- 16652797
TI  - INFLUENCE OF POTASSIUM NITRATE ON NODULE FORMATION AND NITROGEN FIXATION BY
      CLOVER.

PMID- 16652798
TI  - INFLUENCE OF SOME ENVIRONMENTAL CONDITIONS ON THE GROWTH OF EXCISED ROOT TIPS OF
      WHEAT SEEDLINGS IN LIQUID MEDIA.

PMID- 16652799
TI  - ROLE OF "NUTRILITES" IN THE NUTRITION OF MOLDS AND OTHER FUNGI.

PMID- 16652801
TI  - RELATION OF WESTERN YELLOW PINE SEEDLINGS TO THE REACTION OF THE CULTURE
      SOLUTION.

PMID- 16652800
TI  - FURTHER NOTES ON THE NUTRIENT REQUIREMENTS AND THE HISTOLOGY OF THE CRANBERRY,
      WITH SPECIAL REFERENCE TO THE SOURCES OF NITROGEN.

PMID- 16652802
TI  - ABSORPTION OF OXYGEN BY ROOTS WHEN THE SHOOT IS IN DARKNESS OR IN LIGHT.

PMID- 16652803
TI  - COMPARISON OF EXISTING METHODS FOR THE DETERMINATION OF AMMONIA NITROGEN AND
      THEIR ADAPTABILITY TO PLANT JUICE.

PMID- 16652804
TI  - MANGANESE ESSENTIAL FOR THE GROWTH OF LEMNA MAJOR.

PMID- 16652805
TI  - CARBOHYDRATE CONTENT OF TOMATO FRUIT.

PMID- 16652806
TI  - RELATION BETWEEN THE GREEN AND THE YELLOW PIGMENTS IN CHLOROTIC LEAVES.

PMID- 16652807
TI  - A MICRO-METHOD FOR NITROGEN IN PLANT MATERIAL.

PMID- 16652808
TI  - STUDIES OF THE HARDINESS OF PLANTS: A MODIFICATION OF THE NEWTON PRESSURE METHOD
      FOR SMALL SAMPLES.

PMID- 16652809
TI  - THE OPTICAL LEVER AS A TOOL IN PHYSIOLOGICAL STUDIES.

PMID- 16652810
TI  - CALLUSING AND ROOTING OF COTTON STEM CUTTINGS.

PMID- 16652811
TI  - RESPONSE OF IRIS TO SOIL REACTION.

PMID- 16652812
TI  - GROWTH OF TREE SEEDLINGS IN RELATION TO LIGHT INTENSITY AND CONCENTRATION OF
      NUTRIENT SOLUTION.

PMID- 16652813
TI  - METHODS OF MEASURING STRAWBERRY LEAF AREAS.

PMID- 16652814
TI  - NOTES.

PMID- 16652816
TI  - PLASTID STUDIES IN GENETIC TYPES OF MAIZE: ARGENTIA CHLOROPHYLL.

PMID- 16652815
TI  - SEASONAL ABSORPTION OF NUTRIENT SALTS BY THE FRENCH PRUNE GROWN IN SOLUTION
      CULTURES.

PMID- 16652817
TI  - EFFECT OF SEVERAL ENVIRONMENTAL FACTORS ON THE HARDENING OF PLANTS.

PMID- 16652818
TI  - INFLUENCE OF VARIOUS NITROGENOUS COMPOUNDS AND MANNITOL ON NODULE FORMATION BY
      CLOVER.

PMID- 16652819
TI  - MANGANESE AND THE GROWTH OF LEMNA.

PMID- 16652820
TI  - HENRI LOUIS DUHAMEL DUMONCEAU.

PMID- 16652821
TI  - NITROGEN CHANGES IN STORED ALCOHOLIC EXTRACTS OF PLANT TISSUES.

PMID- 16652822
TI  - CORRELATION OF SPECIFIC HEAT AND PERCENTAGE OF WATER IN APPLE WOOD.

PMID- 16652823
TI  - FIELD PROPAGATION OF COTTON BY MEANS OF GRAFTS.

PMID- 16652824
TI  - NOTES.

PMID- 16652825
TI  - PHYSIOLOGICAL ANATOMY, TYPE, VARIETY, AND MATURITY OF CITRUS FRUITS AS AFFECTING
      QUALITY OF PREPARED JUICES.

PMID- 16652826
TI  - SIEVE-TUBE STRUCTURE AND TRANSLOCATION IN THE POTATO.

PMID- 16652828
TI  - EFFECT OF SOIL TYPE AND AERATION UPON ROOT SYSTEMS OF CERTAIN AQUATIC PLANTS.

PMID- 16652827
TI  - SAP HYDRAULICS.

PMID- 16652829
TI  - INFLUENCE OF LEAF DESTRUCTION BY SULPHUR DIOXIDE AND BY CLIPPING ON YIELD OF
      ALFALFA.

PMID- 16652830
TI  - PHOTOSYNTHESIS IN VARIOUS PORTIONS OF THE SPECTRUM.

PMID- 16652831
TI  - EFFECT OF LIGHT ON THE BIOELECTRIC POTENTIALS OF ISOLATED ELODEA LEAVES.

PMID- 16652832
TI  - RELATION OF HYDROPHILIC COLLOIDS TO HARDINESS IN CABBAGE, BRUSSELS SPROUTS, AND
      ALFALFA PLANTS AS SHOWN BY THE DYE ADSORPTION TEST.

PMID- 16652833
TI  - STIMULATIVE EFFECTS OF X-RAYS ON PLANT GROWTH.

PMID- 16652834
TI  - DECREASING HARDINESS OF WINTER WHEAT IN RELATION TO PHOTOSYNTHESIS, DEFOLIATION,
      AND WINTER INJURY.

PMID- 16652835
TI  - FURTHER EVIDENCE THAT BORON IS ESSENTIAL FOR THE GROWTH OF LETTUCE.

PMID- 16652836
TI  - RAPID COLORIMETRIC DETERMINATION OF POTASSIUM IN PLANT TISSUES.

PMID- 16652837
TI  - A NEW METHOD AND INSTRUMENT FOR THE QUANTITATIVE DETERMINATION OF CHLOROPHYLL.

PMID- 16652838
TI  - GASOMETRIC METHOD OF ESTIMATING OXIDASE ACTIVITY.

PMID- 16652839
TI  - LEAF-WRINKLE, A NUTRITIONAL DISORDER OF SOY BEAN.

PMID- 16652841
TI  - RELATIVE INFLUENCE OF NITRATE AND AMMONIACAL NITROGEN UPON INTAKE OF CALCIUM BY
      TOBACCO PLANTS.

PMID- 16652840
TI  - THE TROPOGRAPH AND ITS USE.

PMID- 16652842
TI  - NOTES.

PMID- 16652843
TI  - COMPARATIVE RESPONSES OF LONG-DAY AND SHORT-DAY PLANTS TO RELATIVE LENGTH OF DAY
      AND NIGHT.

PMID- 16652845
TI  - DATE OF FLOWERING AS AFFECTED BY CLIMATIC TEMPERATURE.

PMID- 16652844
TI  - EFFECTS OF STARVATION ON DISTRIBUTION OF MINERAL NUTRIENTS IN FRENCH PRUNE TREES
      GROWN IN CULTURE SOLUTIONS.

PMID- 16652846
TI  - EFFECT OF FREQUENT CLIPPING ON THE DEVELOPMENT OF CERTAIN GRASS SEEDLINGS.

PMID- 16652847
TI  - QUANTITATIVE RELATION BETWEEN CHLOROPHYLL AND IRON IN GREEN AND CHLOROTIC PEAR
      LEAVES.

PMID- 16652848
TI  - INDIRECT COLORIMETRIC METHOD FOR THE DETERMINATION OF CALCIUM.

PMID- 16652849
TI  - POSSIBLE CHANGES IN THE WAXLIKE COATING OF APPLES CAUSED BY CERTAIN SPRAY AND
      OTHER TREATMENTS.

PMID- 16652850
TI  - GAS INJURY TO PURE CULTURES OF SPIRODELA.

PMID- 16652851
TI  - OCCURRENCE OF DULCITOL IN IRIDEAE LAMINARIOIDES (RHODOPHYCEAE).

PMID- 16652852
TI  - MOVEMENT OF ORGANIC MATERIALS IN PLANTS: A CORRECTION.

PMID- 16652853
TI  - NOTES.

PMID- 16652854
TI  - CONCENTRATIONS OF INORGANIC IONS AS RELATED TO GROWTH OF EXCISED ROOT-TIPS OF
      WHEAT SEEDLINGS.

PMID- 16652856
TI  - PHOTODYNAMICALLY INDUCED TROPISMS IN PLANT ROOTS.

PMID- 16652855
TI  - ACIDITY AND ALKALINITY PRODUCED BY CHANGES IN THE NITROGEN, SULPHUR, AND CARBON
      CYCLES.

PMID- 16652857
TI  - NUTRIENT ELEMENTS USED BY LEAVES AND GROWTH OF APPLE TREES.

PMID- 16652858
TI  - CONTROLLED THERMOSTATS FOR PHYSIOLOGICAL STUDIES AT LOW, NON-FREEZING
      TEMPERATURES.

PMID- 16652859
TI  - NEW METHOD OF ARRANGING EXPERIMENTS WITH VEGETABLES IN SAND CULTURES WITH FLOWING
      SOLUTION.

PMID- 16652860
TI  - CHARACTER OF HEMICELLULOSE IN CERTAIN FRUIT TREES.

PMID- 16652861
TI  - EXAMINATION OF STARCH AND HEMICELLULOSE EXTRACTS FROM APPLE WOOD.

PMID- 16652862
TI  - DETECTION AND ESTIMATION OF FORMALDEHYDE WITHIN THE CELL OF A GREEN PLANT BY THE
      ALLISON APPARATUS.

PMID- 16652864
TI  - RELATIONS OF GERMINATING SOY BEANS TO TEMPERATURE AND LENGTH OF INCUBATION TIME.

PMID- 16652863
TI  - NOTES.

PMID- 16652865
TI  - HYDRATION OF SOLUTE IONS IN RELATION TO ACIDITY, ALKALINITY, AND pH.

PMID- 16652866
TI  - INFLUENCE OF SHORTER LIGHT RAYS UPON ABSORPTION OF NITRATE BY THE YOUNG WHEAT
      PLANT.

PMID- 16652867
TI  - AMOUNTS OF BOUND AND FREE WATER IN AN ORGANIC COLLOID AT DIFFERENT DEGREES OF
      HYDRATION.

PMID- 16652868
TI  - GRADIENT COMPOSITION OF ROSE SHOOTS FROM TIP TO BASE.

PMID- 16652869
TI  - SIGNIFICANCE OF TRANSPIRATION.

PMID- 16652870
TI  - EFFECT OF SOFT X-RAYS ON GERMINATION OF WHEAT SEEDS.

PMID- 16652871
TI  - ABSORPTION SPECTRA OF ALPHA AND BETA CAROTENES AND LEAF XANTHOPHYLL AT ROOM AND
      LIQUID NITROGEN TEMPERATURES.

PMID- 16652872
TI  - SOLUBLE SOLIDS IN THE WATERMELON.

PMID- 16652873
TI  - NOTES.

PMID- 16652875
TI  - CHLOROPHYLL PRODUCTION UNDER VARIOUS ENVIRONMENTAL CONDITIONS.

PMID- 16652874
TI  - FACTORS AFFECTING ASSIMILATION OF AMMONIUM AND NITRATE NITROGEN, PARTICULARLY IN
      TOMATO AND APPLE.

PMID- 16652876
TI  - RESPONSES OF KENTUCKY BLUEGRASS TO VARIATIONS IN TEMPERATURE, LIGHT, CUTTING, AND
      FERTILIZING.

PMID- 16652877
TI  - NUTRITIONAL REQUIREMENTS OF THE ROOT-ROT FUNGUS, PHYMATOTRICHUM OMNIVORUM.

PMID- 16652878
TI  - EFFECTS OF HUMIDITY ON METABOLISM IN TOMATO AND APPLE.

PMID- 16652879
TI  - THE SOIL AS DIRECT SOURCE OF CARBON DIOXIDE FOR ORDINARY PLANTS.

PMID- 16652880
TI  - CAUSES OF BLIND WOOD IN ROSES.

PMID- 16652881
TI  - RELATION BETWEEN ROOT RESPIRATION AND ABSORPTION.

PMID- 16652882
TI  - CARBOHYDRATE-NITROGEN AND BASE ELEMENT RELATIONSHIPS OF PEAS GROWN IN WATER
      CULTURE UNDER VARIOUS LIGHT EXPOSURES.

PMID- 16652883
TI  - APPLICATION OF CALORIMETRIC METHODS TO ECOLOGICAL RESEARCH.

PMID- 16652885
TI  - METABOLISM OF ETIOLATED SEEDLINGS AS AFFECTED BY AMMONIUM NUTRITION.

PMID- 16652884
TI  - CARBON DIOXIDE CONTENT OF THE GAS FROM PEA PODS.

PMID- 16652886
TI  - PRODUCTION OF ALCOHOL AND ACETALDEHYDE BY TOMATOES.

PMID- 16652887
TI  - COMPARISON OF THE HEATING AND FREEZING METHODS OF KILLING PLANT MATERIAL FOR
      CRYOSCOPIC DETERMINATIONS.

PMID- 16652888
TI  - INFLUENCE OF THYROXIN ON THE GROWTH OF PLANTS.

PMID- 16652890
TI  - LATERAL WATER TRANSFER IN LEAVES OF GINKGO BILOBA.

PMID- 16652889
TI  - EFFECT OF HIGH FREQUENCY SOUND WAVES ON OXIDASE ACTIVITY.

PMID- 16652891
TI  - COMPARISON OF ANATOMICAL AND HISTOLOGICAL DIFFERENCES BETWEEN ROOTS OF BARLEY
      GROWN IN AERATED AND IN NON-AERATED CULTURE SOLUTIONS.

PMID- 16652893
TI  - NOTES.

PMID- 16652892
TI  - TOLERANCE OF LIQUID-AIR TEMPERATURES BY SEEDS OF HIGHER PLANTS FOR SIXTY DAYS.

PMID- 16652894
TI  - SOME EFFECTS OF POTASSIUM UPON THE GROWTH OF SUGAR CANE AND UPON THE ABSORPTION
      AND MIGRATION OF ASH CONSTITUENTS.

PMID- 16652895
TI  - SOME EFFECTS OF POTASSIUM UPON THE AMOUNTS OF PROTEIN AND AMINO FORMS OF
      NITROGEN, SUGARS, AND ENZYME ACTIVITY OF SUGAR CANE.

PMID- 16652896
TI  - GERMINATION OF THE RED SPRUCE.

PMID- 16652897
TI  - CARBOHYDRATE AND NITROGEN RELATIONS IN WHEAT PLANTS WITH REFERENCE TO TYPE OF
      GROWTH UNDER DIFFERENT ENVIRONMENTAL CONDITIONS.

PMID- 16652898
TI  - PHYSIOLOGICAL ASPECTS OF THE EFFECT OF CONTINUOUS SOIL AERATION ON PLANT GROWTH.

PMID- 16652899
TI  - POTENTIALLY UNLIMITED GROWTH OF EXCISED TOMATO ROOT TIPS IN A LIQUID MEDIUM.

PMID- 16652900
TI  - SALT CONCENTRATION AND REVERSIBILITY OF ICE-FORMATION AS RELATED TO THE HARDINESS
      OF WINTER WHEAT.

PMID- 16652901
TI  - EFFECT OF SOIL TEMPERATURE ON TRANSPIRATION IN HELIANTHUS ANNUUS.

PMID- 16652902
TI  - RELATION OF BENZOIC ACID CONTENT AND OTHER CONSTITUENTS OF CRANBERRIES TO KEEPING
      QUALITY.

PMID- 16652903
TI  - EFFECT OF ETHYLENE, ETHYLENE CHLOROHYDRIN, AND ULTRA-VIOLET LIGHT ON CARBOHYDRATE
      CONTENT OF STORED APPLES.

PMID- 16652904
TI  - LONG AND SHORT WAVE-LENGTH LIMITS OF PHOTOSYNTHESIS.

PMID- 16652905
TI  - EVAPORATION IN ITS THERMODYNAMIC RELATION TO THE COHESION THEORY AND TO
      IMBIBITIONAL AND OSMOTIC PRESSURES OF CELL CONSTITUENTS.

PMID- 16652906
TI  - PREPARATION OF HUMATE IRON AND OTHER HUMATE METALS.

PMID- 16652907
TI  - CHEMICAL CHANGES IN CARROTS DURING GROWTH.

PMID- 16652908
TI  - APPLICATION OF QUANTITATIVE SPECTRAL ANALYSES TO BINARY MIXTURES OF THE COMMON
      CAROTENOIDS.

PMID- 16652909
TI  - WHAT THE ORGANIC CHEMIST CAN DO FOR PLANT PHYSIOLOGY.

PMID- 16652910
TI  - A LARGE-CAPACITY DRYING OVEN WITH CONSTANT UNIFORM TEMPERATURE AND FORCED
      VENTILATION.

PMID- 16652911
TI  - QUANTITATIVE ABSORPTION SPECTRA OF THE COMMON CAROTENOIDS.

PMID- 16652912
TI  - NOTES.

PMID- 16652913
TI  - PENETRATION AND ACCUMULATION OF PETROLEUM SPRAY OILS IN THE LEAVES, TWIGS, AND
      FRUIT OF CITRUS TREES.

PMID- 16652914
TI  - CARBOHYDRATE-NITROGEN RATIOS WITH RESPECT TO THE SEXUAL EXPRESSION OF HEMP.

PMID- 16652915
TI  - LOSSES TO THE CORN CROP CAUSED BY LEAF INJURY.

PMID- 16652916
TI  - FACTORS IN ELONGATION AND EXPANSION UNDER REDUCED LIGHT INTENSITY.

PMID- 16652917
TI  - THE COHESION THEORY OF TRANSPIRATION.

PMID- 16652918
TI  - FREEZING PHENOMENA IN CRESOAP EMULSIONS OF PETROLEUM OILS.

PMID- 16652919
TI  - PRODUCTION OF VITAMINS BY A PURE CULTURE OF CHLOROCOCCUM GROWN IN DARKNESS ON A
      SYNTHETIC MEDIUM.

PMID- 16652920
TI  - PREPARATION OF AQUEOUS EXTRACTS OF SOLUBLE NITROGEN FROM PLANT TISSUES.

PMID- 16652921
TI  - RELATION OF CERTAIN AMINO ACIDS TO CARBON DIOXIDE AND MYCELIUM PRODUCTION OF
      FUSARIUM OXYSPORUM.

PMID- 16652922
TI  - RESPIRATORY RATE AND ENZYME ACTIVITY AS RELATED TO THE HARDENED CONDITION OF
      PLANTS.

PMID- 16652923
TI  - METHOD FOR THE PREPARATION OF GREEN PLANT MATERIAL FOR THE EXTRACTION OF JUICES.

PMID- 16652925
TI  - GOTTLIEB HABERLANDT.

PMID- 16652924
TI  - NUCLEAR DIVISION IN TRADESCANTIA VIRGINIANA.

PMID- 16652926
TI  - DEMONSTRATION OF SOME OF THE MECHANISMS INVOLVED IN THE ASCENT OF SAP IN PLANTS.

PMID- 16652927
TI  - A NOTE ON FRUITING APPLE SPUR PHYLLOTAXY.

PMID- 16652928
TI  - NOTES.

PMID- 16652929
TI  - Anaerobic metabolism in plants.
AB  - Exposure to oxygen deficits is more widespread in biological systems than is
      commonly believed. Until recently, the general perception of anaerobic metabolism
      was often limited to the induction of alcoholic or lactic acid fermentation as
      the sole biochemical response to hypoxia/anoxia. Developments in the physiology,
      biochemistry, and molecular biology of anaerobic responses in invertebrates,
      lower plants, and higher plants have demonstrated that, depending upon the
      species, anaerobic metabolism may encompass much more than simple glycolytic
      metabolism. Here, recent progress in elucidating the mechanism(s) determining
      tolerance versus intolerance to anaerobic environments in higher plants is
      discussed, drawing most heavily on experimental systems using seeds or seedlings.

PMID- 16652930
TI  - Cadmium-Sensitive Mutants of Arabidopsis thaliana.
AB  - A screening procedure for identifying Cd-sensitive mutants of Arabidopsis
      thaliana is described. With this procedure, two Cd-sensitive mutants were
      isolated. These represent independent mutations in the same locus, referred to as
      CAD1. Genetic analysis has shown that the sensitive phenotype is recessive to the
      wild type and segregates as a single Mendelian locus. Crosses of the mutant to
      marker strains showed that the mutation is closely linked to the tt3 locus on
      chromosome 5. In addition to Cd, the mutants are also significantly more
      sensitive to mercuric ions and only slightly more sensitive to Cu and Zn, while
      being no more sensitive than the wild type to Mn, thus indicating a degree of
      specificity in the mechanism affected by the mutation. Undifferentiated callus
      tissue is also Cd sensitive, suggesting that the mutant phenotype is expressed at
      the cellular level. Both wild-type and mutant plants showed increased sensitivity
      to Cd in the presence of buthionine sulfoximine, an inhibitor of the biosynthesis
      of the cadmium-binding (gamma-glutamylcysteine)(n)-glycine peptides, suggesting
      that the mutant is still able to synthesize these peptides. However, the effects
      of a cad1 mutation and buthionine sulfoximine together on cadmium sensitivity are
      essentially nonadditive, indicating that they may affect different aspects of the
      same detoxification mechanism. Assays of Cd uptake by intact plants indicate that
      the mutant is deficient in its ability to sequester Cd.

PMID- 16652931
TI  - The decrease in auxin polar transport down the lupin hypocotyl could produce the
      indole-3-acetic Acid distribution responsible for the elongation growth pattern.
AB  - The variation of indole-3-acetic acid (IAA) transport along Lupinus albus L.
      hypocotyls was studied using decapitated seedlings and excised sections. To
      confirm that the mobile species was IAA and not IAA metabolites, dual isotope
      labeled IAAs, [5-(3)H]IAA + [1-(14)C]IAA, were used. After apical application to
      decapitated seedlings, the longitudinal distribution of both isotopes at
      different transport periods showed that the velocity of IAA transport was higher
      in the apical, elongating region than in the basal, non-growing region. This
      variation in velocity was not a traumatic consequence of decapitation because
      after application of IAA to the basal region of decapitated seedlings, both the
      velocity and intensity of IAA transport were lower than in the apical treatment.
      The variation in IAA transport down the hypocotyl was confirmed when it was
      measured in excised sections located at different positions along the hypocotyl.
      The velocity and, to a greater extent, the intensity of IAA transport decreased
      from the apical to the basal sections. Consequently, if the amount of IAA
      reaching the apical zones of lupin hypocotyl were higher than the IAA transport
      capacity in the basal zones, accumulation of mobile IAA might be expected in
      zones located above the basal region. In fact, an IAA accumulation occurred in
      the elongating region during the first 4-h period of transport after apical
      treatment with IAA. It is proposed that the fall in IAA transport along the
      hypocotyl might be responsible for the IAA distribution and, consequently, for
      the growth distribution reported in this organ. An indirect proof of this was
      obtained from experiments that showed that the excision of the slowly
      transporting basal zones strongly reduced the growth in the remaining part of the
      organ, whereas excision of the root caused no significant modification in growth
      during a 20-h period.

PMID- 16652932
TI  - Lower growth temperature increases alternative pathway capacity and alternative
      oxidase protein in tobacco.
AB  - Suspension cells of NT1 tobacco (Nicotiana tabacum L. cv bright yellow) have been
      used to study the effect of growth temperature on the CN-resistant,
      salicylhydroxamic acid-sensitive alternative pathway of respiration. Mitochondria
      isolated from cells maintained at 30 degrees C had a low capacity to oxidize
      succinate via the alternative pathway, whereas mitochondria isolated from cells
      24 h after transfer to 18 degrees C displayed, on average, a 5-fold increase in
      this capacity (from 7 to 32 nanoatoms oxygen per milligram protein per minute).
      This represented an increase in alternative pathway capacity from 18 to 45% of
      the total capacity of electron transport. This increased capacity was lost upon
      transfer of cells back to 30 degrees C. A monoclonal antibody to the terminal
      oxidase of the alternative pathway (the alternative oxidase) from Sauromatum
      guttatum (T.E. Elthon, R.L. Nickels, L. McIntosh [1989] Plant Physiology 89: 1311
      1317) recognized a 35-kilodalton mitochondrial protein in tobacco. There was an
      excellent correlation between the capacity of the alternative path in isolated
      tobacco mitochondria and the levels of this 35-kilodalton alternative oxidase
      protein. Cycloheximide could inhibit both the increased level of the 35
      kilodalton alternative oxidase protein and the increased alternative pathway
      capacity normally seen upon transfer to 18 degrees C. We conclude that transfer
      of tobacco cells to the lower temperature increases the capacity of the
      alternative pathway due, at least in part, to de novo synthesis of the 35
      kilodalton alternative oxidase protein.

PMID- 16652933
TI  - Cell Wall Structure in Cells Adapted to Growth on the Cellulose-Synthesis
      Inhibitor 2,6-Dichlorobenzonitrile : A Comparison between Two Dicotyledonous
      Plants and a Graminaceous Monocot.
AB  - Our previous work (E. Shedletzky, M. Shmuel, D.P. Delmer, D.T.A. Lamport [1990]
      Plant Physiol 94:980-987) showed that suspension-cultured tomato cells adapted to
      growth on the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile (DCB) have a
      markedly altered cell wall composition, most notably a markedly reduced level of
      the cellulose-xyloglucan network. This study compares the adaptation to DCB of
      two cell lines from dicots (tomato [Lycopersicon esculentum] and tobacco
      [Nicotiana tabacum]) and a Graminaceous monocot (barley [Hordeum bulbosum]
      endosperm). The difference in wall structures between the dicots and the monocot
      is reflected in the very different types of wall modifications induced by growth
      on DCB. The dicots, having reduced levels of cellulose and xyloglucan, possess
      walls the major integrity of which is provided by Ca(2+)-bridged pectates because
      protoplasts can be prepared from these cells simply by treatment with divalent
      cation chelator and a purified endopolygalacturonase. The tensile strength of
      these walls is considerably less than walls from nonadapted cells, but wall
      porosity is not altered. In contrast, walls from adapted barley cells contain
      very little pectic material and normal to elevated levels of noncellulosic
      polysaccharides compared with walls from nonadapted cells. Surprisingly, they
      have tensile strengths higher than their nonadapted counterpart, although
      cellulose levels are reduced by 70%. Evidence is presented that these walls
      obtain their additional strength by an altered pattern of cross-linking of
      polymers involving phenolic components. Such cross-linking may also explain the
      observation that the porosity of these walls is also considerably reduced. Cells
      of adapted lines of both the dicots and barley are resistant to plasmolysis,
      suggesting that they possess very strong connections between the wall and the
      plasma membrane.

PMID- 16652934
TI  - Spread of engineered genes to wild relatives.

PMID- 16652935
TI  - 1-Aminocyclopropane-1-Carboxylic Acid Transported from Roots to Shoots Promotes
      Leaf Abscission in Cleopatra Mandarin (Citrus reshni Hort. ex Tan.) Seedlings
      Rehydrated after Water Stress.
AB  - The effect of water stress and subsequent rehydration on 1-aminocyclopropane-1
      carboxylic acid (ACC) content, ACC synthase activity, ethylene production, and
      leaf abscission was studied in Cleopatra mandarin (Citrus reshni Hort. ex Tan.)
      seedlings. Leaf abscission occurred when drought-stressed plants were allowed to
      rehydrate, whereas no abscission was observed in plants under water stress
      conditions. In roots of water-stressed plants, a high ACC accumulation and an
      increase in ACC synthase activity were observed. Neither increase in ACC content
      nor significant ethylene production were detected in leaves of water-stressed
      plants. After rehydration, a sharp rise in ACC content and ethylene production
      was observed in leaves of water-stressed plants. Content of ACC in xylem fluid
      was 10-fold higher in plants rehydrated for 2 h after water stress than in
      nonstressed plants. Leaf abscission induced by rehydration after drought stress
      was inhibited when roots or shoots were treated before water stress with
      aminooxyacetic acid (AOA, inhibitor of ACC synthase) or cobalt ion (inhibitor of
      ethylene-forming enzyme), respectively. However, AOA treatments to shoots did not
      suppress leaf abscission. The data indicate that water stress promotes ACC
      synthesis in roots of Cleopatra mandarin seedlings. Rehydration of plants results
      in ACC transport to the shoots, where it is oxidized to ethylene. Subsequently,
      this ethylene induces leaf abscission.

PMID- 16652936
TI  - Purification of Multiple Forms of Glutathione Reductase from Pea (Pisum sativum
      L.) Seedlings and Enzyme Levels in Ozone-Fumigated Pea Leaves.
AB  - Glutathione reductase was purified from pea seedlings using a procedure that
      included 2',5'-ADP Sepharose, fast protein liquid chromatography (FPLC)-anion
      exchange, and FPLC-hydrophobic interaction chromatography. The purified
      glutathione reductase was resolved into six isoforms by chromatofocusing. The
      isoform eluting with an isoelectric point of 4.9 accounted for 18% of the total
      activity. The five isoforms with isoelectric points between 4.1 and 4.8 accounted
      for 82% of the activity. Purified glutathione reductase from isolated, intact
      chloroplasts also resolved into six isoforms after chromatofocusing. The isoform
      eluting at pH 4.9 constituted a minor fraction of the total activity. By
      comparing the chromatofocusing profile of the seedling extract with that of the
      chloroplast extract, we inferred that the least acidic isoform was extraplastidic
      and that the five isoforms eluting from pH 4.1 to 4.8 were plastidic. Both the
      plastidic (five isoforms were pooled) and extraplastidic glutathione reductases
      had a native molecular mass of 114 kD. The plastidic glutathione reductase is a
      homodimer with a subunit molecular mass of 55 kD. Both glutathione reductases had
      optimum activity at pH 7.8. The K(m) for the oxidized form of glutathione (GSSG)
      was 56.0 and 33.8 mum for plastidic and extraplastidic glutathione reductase,
      respectively, at 25 degrees C. The K(m) for NADPH was 4.8 and 4.0 mum for
      plastidic and extraplastidic isoforms, respectively. Antiserum raised against the
      plastidic glutathione reductase recognized a 55-kD polypeptide from purified
      antigen on western blots. In addition to the 55-kD polypeptide, another 36-kD
      polypeptide appeared on western blots of leaf crude extracts and the purified
      extraplastidic isoform. The lower molecular mass polypeptide might represent GSSG
      independent enzyme activity observed on activity-staining gels of crude extracts
      or a protein that has an epitope similar to that in glutathione reductase.
      Fumigation with 75 nL L(-1) ozone for 4 h on 2 consecutive days had no
      significant effect on glutathione reductase activity in peas (Pisum sativum L.).
      However, immunoblotting showed a greater level of glutathione reductase protein
      in extracts from ozone-fumigated plants compared with that in control plants at
      the time when the target concentration was first reached, approximately 40 min
      from the start of the fumigation, and 4 h on the first day of fumigation.

PMID- 16652937
TI  - Arginine decarboxylase of oats is clipped from a precursor into two polypeptides
      found in the soluble enzyme.
AB  - We have examined soluble oat (Avena sativa) arginine decarboxylase by probing its
      structure with polyclonal antibodies that separately recognize amino-terminal and
      carboxyl-terminal antigens and with a monoclonal antibody that immunoprecipitates
      enzyme activity. These experiments indicated that oat arginine decarboxylase is
      clipped from a 66,000-D precursor polypeptide into 42,000- and 24,000-D produce
      polypeptides. Both of these are found in the enzyme and may be held together by
      disulfide bonds. A full-length precursor protein could not be detected in plants
      but could be produced by expression of the cDNA in Escherichia coli. Analysis of
      the expression of the cDNA in E. coli, with antibodies and using pulse labeling
      with [(35)S]methionine, indicated that the bulk of the expressed protein was the
      full-length 66,000-D form. Small amounts of 42,000- and 24,000-D polypeptides
      could also be detected. A reconstruction experiment, adding a radioactively
      labeled full-length protein isolated from E. coli to powdered oat leaves,
      supported the idea that the protein extraction method used for western blots was
      not likely to result in artifactual proteolytic degradation.

PMID- 16652938
TI  - Cytokinin Is Required to Induce the Nitrogen-Dependent Accumulation of mRNAs for
      Phosphoenolpyruvate Carboxylase and Carbonic Anhydrase in Detached Maize Leaves.
AB  - Previous studies with intact maize (Zea mays L.) plants indicated that
      phosphoenolpyruvate carboxylase (PEPC) levels are controlled by nitrogen (N)
      availability and that this regulation is presumably at the transcriptional level
      (B. Sugiharto, K. Miyata, H. Nakamoto, H. Sasakawa, T. Sugiyama [1990] Plant
      Physiol 92: 963-969; B. Sugiharto, T. Sugiyama [1992] Plant Physiol 98: 1403
      1408). In the present study, detached maize leaves were used to investigate
      further the mechanism of N-dependent regulation of gene expression in C(4)
      plants. PEPC and carbonic anhydrase (CA) mRNA levels decreased in leaves detached
      from maize plants. Addition of high nitrate did not prevent this decrease.
      However, the addition of zeatin to solutions bathing the cut ends of the detached
      leaves inhibited the decrease of PEPC and CA mRNA levels. Simultaneous addition
      of high nitrate and zeatin to leaves detached from N-deficient maize plants
      caused a large and rapid increase in PEPC and CA mRNA levels. Zeatin could be
      replaced by benzyladenine, but not by indoleacetic acid or abscisic acid. Both CA
      isozymes were effected and responded in an identical manner. We conclude that
      detached maize leaves provide an excellent experimental system to study the
      mechanism(s) of N-mediated regulation of PEPC and CA gene expression. However,
      zeatin is an essential component of this system.

PMID- 16652939
TI  - Biphasic kinetic behavior of nitrate reductase from heterocystous, nitrogen
      fixing cyanobacteria.
AB  - Nitrate reductase activity from filamentous, heterocyst-forming cyanobacteria
      showed a biphasic kinetic behavior with respect to nitrate as the variable
      substrate. Two kinetic components were detected, the first showing a higher
      affinity for nitrate (K(m), 0.05-0.25 mm) and a lower catalytic activity and the
      second showing a lower affinity for nitrate (K(m), 5-25 mm) and a higher (3- to 5
      fold) catalytic activity. In contrast, among unicellular cyanobacteria, most
      representatives studied exhibited a monophasic, Michaelis-Menten kinetic pattern
      for nitrate reductase activity. Biphasic kinetics remained unchanged with the use
      of different assay conditions (i.e. cell disruption or permeabilization, two
      different electron donors) or throughout partial purification of the enzyme.

PMID- 16652940
TI  - Growth, Gravitropism, and Endogenous Ion Currents of Cress Roots (Lepidium
      sativum L.) : Measurements Using a Novel Three-Dimensional Recording Probe.
AB  - A novel, three-dimensional recording, vibrating probe was used for measuring the
      density and direction of the endogenous ionic current of cress roots (Lepidium
      sativum L.) bathed in low salt media (artificial pond water, APW). Roots
      submerged in regular APW and growing vertically show the following current
      pattern. Current of 0.7 microampere/square centimeter density enters or leaves
      the root cap; the current changes direction frequently. Current of 1.6
      microamperes/square centimeter enters the meristem zone most of the time. Maximum
      current with a density of 2.2 microamperes/square centimeter enters the apical
      elongating zone, i.e. between 0.8 and 1.2 millimeters behind the root tip. The
      current density decreases to 1.4 microamperes/square centimeter at 2 millimeters,
      i.e. in the central elongating zone, and to 1.0 microampere/square centimeter at
      3 millimeters, i.e. in the basal elongating zone. The current direction changes
      from inward to predominantly outward between 1.2 and 3 millimeters behind the
      tip. Measurements on opposite flanks of the roots indicate that the current
      pattern is fairly symmetrical. After placing the roots horizontally, the density
      of the endogenous current remains stable, but the current direction changes at
      the root cap and in the meristem zone. The current leaves the root on the upper
      side and enters on the lower side, causing a highly asymmetrical current pattern
      at the very tip. The current pattern at the upper and lower side further away
      from the tip remains the same as in vertical roots. Roots submerged in low Ca(2+)
      APW show a very different current pattern, no gravitropism, and no change of the
      current pattern after horizontal orientation. In these roots current enters the
      root cap and the basal elongating zone and leaves the apical elongating zone.
      Three conclusions are drawn from these results: First, plant roots elongate by
      two different modes of growth that are correlated with different current
      directions. They grow by cytoplasmic enlargement at sites of inward current and
      by turgor-driven elongation at sites of outward current. Second, a change in the
      current pattern at the root cap and in the meristem zone is a clear indicator of
      later gravitropism. Third, Ca(2+) ions are involved in the gravistimulated change
      in the current pattern, probably affecting the activity of plasmalemma H(+)
      ATPases.

PMID- 16652941
TI  - A wound-inducible potato proteinase inhibitor gene expressed in non-tuber-bearing
      species is not sucrose inducible.
AB  - Sequences homologous to a potato cathepsin D inhibitor cDNA, p749, were
      identified in the genomic DNA of tomato (Lycopersicon esculentum) and of two non
      tuber-bearing potato species (Solanum etuberosum and S. brevidens) by means of
      Southern blot analysis. The expression of these p749 genes in leaves was induced
      at the RNA level in response to wounding. High levels of p749 transcripts were
      detected in polyadenylated RNA extracted from locally wounded leaves 12 h after
      wounding. Systemic induction of the cathepsin D inhibitor gene also occurred in
      nonwounded leaves of wounded plants. Both potato and tomato leaves treated with
      the oligosaccharide chitosan showed an induced accumulation of p749 transcripts.
      Even though the cathepsin D inhibitor genes from tomato and from non-tuber
      bearing potato species are wound inducible, they could not be induced in leaf
      explants cultured on medium containing very high concentrations of sucrose. Only
      leaf explants from the tuber-bearing potato (S. tuberosum) accumulated p749
      transcripts when cultured on high sucrose medium. A sequence related to the 22-kD
      potato proteinase inhibitor cDNA, p34021, was identified in tomato by means of
      genomic Southern blot analysis. Northern blot hybridization showed that p34021
      transcripts accumulated in potato (S. tuberosum) leaf explants, but not in tomato
      explants, when cultured on high sucrose medium. This study demonstrates that the
      expression of a potato cathepsin D inhibitor gene in tomato and in non-tuber
      bearing potato species is wound inducible, but not sucrose inducible.

PMID- 16652942
TI  - Phytochrome-mediated phototropism in de-etiolated seedlings : occurrence and
      ecological significance.
AB  - Phototropic responses to broadband far red (FR) radiation were investigated in
      fully de-etiolated seedlings of a long-hypocotyl mutant (lh) of cucumber (Cucumis
      sativus L.), which is deficient in phytochrome-B, and its near isogenic wild type
      (WT). Continuous unilateral FR light provided against a background of white light
      induced negative curvatures (i.e. bending away from the FR light source) in
      hypocotyls of WT seedlings. This response was fluence-rate dependent and was
      absent in the lh mutant, even at very high fluence rates of FR. The phototropic
      effect of FR light on WT seedlings was triggered in the hypocotyls and occurred
      over a range of fluence rates in which FR was very effective in promoting
      hypocotyl elongation. FR light had no effect on elongation of lh-mutant
      hypocotyls. Seedlings grown in the field showed negative phototropic responses to
      the proximity of neighboring plants that absorbed blue (B) and red light and back
      reflected FR radiation. The bending response was significantly larger in WT than
      in lh seedlings. Responses of WT and lh seedlings to lateral B light were very
      similar; however, elimination of the lateral B light gradients created by the
      proximity of plant neighbors abolished the negative curvature only in the case of
      lh seedlings. More than 40% of the total hypocotyl curvature induced in WT
      seedlings by the presence of neighboring plants was present after equilibrating
      the fluence rates of B light received by opposite sides of the hypocotyl. These
      results suggest that: (a) phytochrome functions as a phototropic sensor in de
      etiolated plants, and (b) in patchy canopy environments, young seedlings actively
      project new leaves into light gaps via stem bending responses elicited by the B
      absorbing photoreceptor(s) and phytochrome.

PMID- 16652943
TI  - Purification and Properties of Fructokinase from Developing Tubers of Potato
      (Solanum tuberosum L.).
AB  - Fructokinase has been purified from developing potato (Solanum tuberosum L.)
      tubers by a combination of hydrophobic interaction, affinity chromatography, and
      gel filtration. The protein has a native molecular mass of approximately 70 kD
      but is apparently a dimer. Ion-exchange chromatography and two-dimensional
      western blots resolved three major fructokinases, designated FK-I, FK-II, and FK
      III in order of their elution from a Mono-Q column. Fructokinase activity proved
      labile when proteins were purified in the absence of fructose. Kinetically, FKs
      I, II, and III all have broad pH optima with peaks at about pH 8.5. The enzymes
      have a high specificity for fructose (K(m) values ranging from 0.041 to 0.128
      mm), and can utilize a range of nucleoside triphosphates. Unlike FKs I and II, FK
      III is not inhibited by fructose concentrations in excess of 1 mm. MgADP
      inhibited activity of the three FKs (between 68 and 75% inhibition at 1.0 mm),
      whereas fructose 6-P caused inhibition at concentrations of 10 mm. There were no
      regulatory effects observed with a range of other metabolites. K(+) (10 mm)
      activated FK-I by 4-fold and FKs II and III by only about 50%.

PMID- 16652944
TI  - Transport Processes and Corresponding Changes in Metabolite Levels in Relation to
      Starch Synthesis in Barley (Hordeum vulgare L.) Etioplasts.
AB  - Intact etioplasts with an intactness of 85% and with a cytosolic and a
      mitochondrial contamination of less than 10% were isolated from 8-d-old dark
      grown barley (Hordeum vulgare) leaves. These plastids contained starch equivalent
      to 21.5 mumol of glucose per mg protein. From various likely precursors applied
      to isolated etioplasts, only dihydroxyacetone phosphate (DHAP) had significant
      effects on metabolite levels and on the internal ATP/ADP ratio. The concentration
      dependence of DHAP uptake exhibited saturation characteristics with half
      saturation at 0.36 mm DHAP and a maximal velocity of 6.6 mumol mg(-1) of protein
      h(-1). The transport was significantly inhibited by inorganic phosphate,
      pyridoxal-5'-phosphate, and 4,4'-diisothiocyano-2,2'-stilbenedisulfonate. The
      rate of glucose-6-phosphate uptake was much lower and not saturable up to a
      concentration of 10 mm. Exogenously applied [(14)C]DHAP was incorporated into
      starch at a rate of 0.14 mumol of DHAP mg(-1) of protein h(-1). Enzyme activities
      required to convert DHAP into starch were found to be present in etioplasts.
      Furthermore, enzymes generating ATP from DHAP for ADPglucose synthesis were also
      detected. Finally, a scheme is presented suggesting DHAP uptake to serve both as
      carbon skeleton and as energy source for starch synthesis, mediated by a
      translocator with properties similar to those of the triose phosphate
      translocator from chloroplasts.

PMID- 16652945
TI  - A Comparison of Dark Respiration between C(3) and C(4) Plants.
AB  - Lower respiratory costs were hypothesized as providing an additional benefit in
      C(4) plants compared to C(3) plants due to less investment in proteins in C(4)
      leaves. Therefore, photosynthesis and dark respiration of mature leaves were
      compared between a number of C(4) and C(3) species. Although photosynthetic rates
      were generally greater in C(4) when compared to C(3) species, no differences were
      found in dark respiration rates of individual leaves at either the beginning or
      after 16 h of the dark period. The effects of nitrogen on photosynthesis and
      respiration of individual leaves and whole plants were also investigated in two
      species that occupy similar habitats, Amaranthus retroflexus (C(4)) and
      Chenopodium album (C(3)). For mature leaves of both species, there was no
      relationship between leaf nitrogen and leaf respiration, with leaves of both
      species exhibiting a similar rate of decline after 16 h of darkness. In contrast,
      leaf photosynthesis increased with increasing leaf nitrogen in both species, with
      the C(4) species displaying a greater photosynthetic response to leaf nitrogen.
      For whole plants of both species grown at different nitrogen levels, there was a
      clear linear relationship between net CO(2) uptake and CO(2) efflux in the dark.
      The dependence of nightly CO(2) efflux on CO(2) uptake was similar for both
      species, although the response of CO(2) uptake to leaf nitrogen was much steeper
      in the C(4) species, Amaranthus retroflexus. Rates of growth and maintenance
      respiration by whole plants of both species were similar, with both species
      displaying higher rates at higher leaf nitrogen. There were no significant
      differences in leaf or whole plant maintenance respiration between species at any
      temperature between 18 and 42 degrees C. The data suggest no obvious differences
      in respiratory costs in C(4) and C(3) plants.

PMID- 16652946
TI  - Purification and Characterization of Wheat beta(2-->1) Fructan:Fructan Fructosyl
      Transferase Activity.
AB  - Fructans are the major storage carbohydrate in vegetative tissues of wheat
      (Triticum aestivum L.). Fructan:fructan fructosyl transferase (FFT) catalyzes
      fructosyl transfer between fructan molecules to elongate the fructan chain. The
      objective of this research was to isolate this activity in wheat. Wheat (cv
      Caldwell) plants grown at 25 degrees C for 3 weeks were transferred to 10 degrees
      C to induce fructan synthesis. From the leaf blades kept at 10 degrees C for 4
      days, fructosyl transferase activity was purified using salt precipitation and a
      series of chromatographic procedures including size exclusion, anion-exchange,
      and affinity chromatography. The transferase activity was free from invertase and
      other fructan-metabolizing activities. Fructosyl transferase had a broad pH
      spectrum with a peak activity at 6.5. The temperature optimum was 30 degrees C.
      The activity was specific for fructosyl transfer from beta(2-->1)-linked 1
      kestose or fructan to sucrose and beta(2-->1) fructosyl transfer to other
      fructans (1-FFT). Fructosyl transfer from oligofructans to sucrose was most
      efficient when 1-kestose was used as donor molecule and declined as the degree of
      polymerization of the donor increased from 3 to 5. 1-FFT catalyzed the in vitro
      synthesis of inulin tetra- and penta-saccharides from 1-kestose; however,
      formation of the tetrasaccharide was greatly reduced at high sucrose
      concentration. 6-Kestose could not act as donor molecule, but could accept a
      fructosyl moiety from 1-kestose to produce bifurcose and a tetrasaccharide having
      a beta(2-->1) fructose attached to the terminal fructose of 6-kestose. The role
      of this FFT activity in the synthesis of fructan in wheat is discussed.

PMID- 16652947
TI  - Use of positive pressures to establish vulnerability curves : further support for
      the air-seeding hypothesis and implications for pressure-volume analysis.
AB  - Loss of hydraulic conductivity occurs in stems when the water in xylem conduits
      is subjected to sufficiently negative pressure. According to the air-seeding
      hypothesis, this loss of conductivity occurs when air bubbles are sucked into
      water-filled conduits through micropores adjacent to air spaces in the stem.
      Results in this study showed that loss of hydraulic conductivity occurred in stem
      segments pressurized in a pressure chamber while the xylem water was under
      positive pressure. Vulnerability curves can be defined as a plot of percentage
      loss of hydraulic conductivity versus the pressure difference between xylem water
      and the outside air inducing the loss of conductivity. Vulnerability curves were
      similar whether loss of conductivity was induced by lowering the xylem water
      pressure or by raising the external air pressure. These results are consistent
      with the air-seeding hypothesis of how embolisms are nucleated, but not with the
      nucleation of embolisms at hydrophobic cracks because the latter requires
      negative xylem water pressure. The results also call into question some basic
      underlying assumptions used in the determination of components of tissue water
      potential using "pressure-volume" analysis.

PMID- 16652948
TI  - Carbon Partitioning in a Flaveria linearis Mutant with Reduced Cytosolic Fructose
      Bisphosphatase.
AB  - Oxygen sensitivity and partitioning of carbon was measured in a mutant line of
      Flaveria linearis that lacks most of the cytosolic fructose-1,6-bisphosphatase
      found in wild-type lines. Photosynthesis of leaves of the mutant line was nearly
      insensitive to O(2), as found before. The mutant plants partitioned 2.5 times
      less carbon into sucrose than the wild type in a pulse chase experiment, with the
      extra carbon going mainly to starch but also to amino acids. From 10 to 50 min
      postlabeling, radioactivity chased out of the amino acid fraction to starch in
      both lines. In the middle of the light period, starch grains were larger in the
      mutant than in the wild type and covered 30% of the chloroplast area as seen with
      an electron microscope. Starch grains were found in both mesophyll and bundle
      sheath chloroplasts in both lines in these C(3)-C(4) intermediate plants. At the
      end of the dark period, the starch levels were considerably reduced from what
      they were in the middle of the light in both lines. The concentration of sucrose
      was higher in the mutant line despite the lack of cytosolic fructose-1,6
      bisphosphatase. The amino acid fraction accounted for about 30% of all label
      following a 10-min chase period. In the mutant line, most of the label was in the
      glycine + serine fraction, with 10% in the alanine fraction. In wild-type leaves,
      35% of the label in amino acids was in alanine. These results indicate that this
      mutant survives the reduced cytosolic fructose-1,6-bisphosphatase activity by
      partitioning more carbon to starch and less to sucrose during the day and
      remobilizing the excess starch at night. However, these results raise two other
      questions about this mutant. First, why is the sucrose concentration high in a
      plant that partitions less carbon to sucrose, and second, why is alanine heavily
      labeled in the wild-type plants but not in the mutant plants?

PMID- 16652949
TI  - Abscisic Acid Elicits the Water-Stress Response in Root Hairs of Arabidopsis
      thaliana.
AB  - Water stress has been shown to cause root hairs to become short and bulbous.
      Because abscisic acid (ABA) mediates a variety of water-stress responses, we
      investigated the response of Arabidopsis thaliana root hairs to ABA. When wild
      type root hairs were treated with ABA, they exhibited the water-stress response.
      The Arabidopsis mutants abi1 and abi2, which are insensitive to ABA at the
      seedling stage, did not display the root hair response. These data suggest that
      ABA may mediate the response of root hairs to water stress. The drought response
      of root hairs resulting in an inhibition of tip growth will provide an easy
      screen to select mutations that are insensitive to ABA and/or involved in tip
      growth.

PMID- 16652950
TI  - The Stimulation of Ethylene Synthesis in Nicotiana tabacum Leaves by the
      Phytotoxin Coronatine.
AB  - Coronatine is a chlorosis-inducing toxin produced by the plant pathogen
      Pseudomonas syringae pv atropurpurea. This bacterium is the causal agent of
      chocolate spot disease, in which brown lesions with chlorotic margins develop on
      the leaves of Lolium multiflorum Lam. Among the many physiological changes to
      plants caused by coronatine is the stimulation of ethylene production from bean
      leaves. The ethyl-substituted side chain of coronatine is an analog of the
      ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC). We have examined
      the question of whether part or all of the released ethylene comes from the
      breakdown of coronatine itself. The rate of ethylene release from leaves of
      Nicotiana tabacum was proportional to the concentration of coronatine applied to
      the leaf surface. The lowest effective concentration of coronatine, applied to
      leaves at 15 pmol cm(-2) of leaf area, resulted in the production of 44 pmol of
      ethylene cm(-2) over a period of 4 h. The maximum rate of ethylene production
      occurred 28 to 32 h after application of coronatine. The specific activity of
      ethylene produced by discs cut from coronatine-treated Nicotiana tabacum leaves
      floating on a solution containing 10 mm [U-(14)C]methionine was consistent with
      its exclusive origin from methionine. ACC accumulated in the coronatine-treated
      tissue. ACC synthase activity increased in Phaseolus aureus hypocotyls during a 6
      h treatment with coronatine. Thus, coronatine induces the synthesis of ethylene
      from methionine.

PMID- 16652951
TI  - Maturation proteins and sugars in desiccation tolerance of developing soybean
      seeds.
AB  - The desiccation-tolerant state in seeds is associated with high levels of certain
      sugars and maturation proteins. The aim of this work was to evaluate the
      contributions of these components to desiccation tolerance in soybean (Glycine
      max [L.] Merrill cv Chippewa 64). When axes of immature seeds (34 d after
      flowering) were excised and gradually dried (6 d), desiccation tolerance was
      induced. By contrast, seeds held at high relative humidity for the same period
      were destroyed by desiccation. Maturation proteins rapidly accumulated in the
      axes whether the seeds were slowly dried or maintained at high relative humidity.
      During slow drying, sucrose content increased to five times the level present in
      the axes of seeds held at high relative humidity (128 versus 25 mug/axis,
      respectively). Stachyose content increased dramatically from barely detectable
      levels upon excision to 483 mug/axis during slow drying but did not increase
      significantly when seeds were incubated at high relative humidity. Galactinol was
      the only saccharide that accumulated to higher levels in axes from seeds
      incubated at high relative humidity relative to axes from seeds that were slowly
      dried. This suggests that slow drying serves to induce the accumulation of the
      raffinose series sugars at a point after galactinol biosynthesis. We conclude
      that stachyose plays an important role in conferring desiccation tolerance.

PMID- 16652952
TI  - Regulation of ascorbate oxidase expression in pumpkin by auxin and copper.
AB  - Ascorbate oxidase expression in pumpkin (Cucurbita spp.) tissues was studied.
      Specific ascorbate oxidase activities in pumpkin leaf and stem tissues were about
      2 and 1.5 times that in the fruit tissues, respectively. In seeds, little
      ascorbate oxidase activity was detected. Northern blot analyses showed an
      abundant ascorbate oxidase mRNA in leaf and stem tissues. Fruit tissues had lower
      levels of ascorbate oxidase mRNA than leaf and stem tissues. Ascorbate oxidase
      mRNA was not detected in seeds. Specific ascorbate oxidase activity gradually
      increased during early seedling growth of pumpkin seeds. The increase was
      accompanied by an increase in ascorbate oxidase mRNA. When ascorbate oxidase
      activity in developing pumpkin fruits was investigated, the activities in
      immature fruits that are rapidly growing at 0, 2, 4, and 7 d after anthesis were
      much higher than those in mature fruits at 14 and 30 d after anthesis. The
      specific activity and mRNA of ascorbate oxidase markedly increased after
      inoculation of pumpkin fruit tissues into Murashige and Skoog's culture medium in
      the presence of an auxin such as 2,4-dichlorophenoxyacetic acid (2,4-D) but not
      in the absence of 2,4-D. In the presence of 10 mg/L of 2,4-D, ascorbate oxidase
      mRNA was the most abundant. Thus, ascorbate oxidase is induced by 2,4-D. These
      results indicate that ascorbate oxidase is involved in cell growth. In pumpkin
      callus, ascorbate oxidase activity could be markedly increased by adding copper.
      Furthermore, immunological blotting showed that the amount of ascorbate oxidase
      protein was also increased by adding copper. However, northern blot analyses
      showed that ascorbate oxidase mRNA was not increased by adding copper. We suggest
      that copper may control ascorbate oxidase expression at translation or at a site
      after translation.

PMID- 16652953
TI  - Ethylene-Induced Polyamine Accumulation in Rice (Oryza sativa L.) Coleoptiles.
AB  - Effects of ethylene on free polyamine biosynthesis in rice (Oryza sativa L. cv
      Taichung Native 1) coleoptiles were investigated in sealed and aerobic
      conditions. In sealed conditions, putrescine increased significantly and
      coincided with ethylene accumulation. Application of ethylene in sealed
      containers promoted putrescine accumulation over that in sealed controls. This
      ethylene-enhanced putrescine accumulation was inhibited by the ethylene action
      inhibitor 2,5-norbornadiene at 4000 muL/L. In aerobic conditions, ethylene and 1
      aminocyclopropane-1-carboxylic acid also induced putrescine accumulation.
      Activity of arginine decarboxylase (EC 4.1.1.19) and S-adenosylmethionine
      decarboxylase (EC 4.1.1.50) increased on exposure to ethylene in aerobic
      conditions. Ornithine decarboxylase (EC 4.1.1.17) activity, however, remained
      unchanged. The ethylene-induced putrescine accumulation was inhibited by 5 x 10(
      4)m alpha-difluromethylarginine, but not by 5 x 10(-4)m alpha
      difluromethylornithine. Apparently, arginine decarboxylase, not ornithine
      decarboxylase, mediates the ethylene-induced putrescine accumulation. The
      increased S-adenosylmethioinine decarboxylase activity, however, did not result
      in a significant spermidine/spermine accumulation. In ethylene-treated
      coleoptiles, the accumulation of putrescine paralleled the increase of coleoptile
      length in both sealed and aerobic conditions. alpha-difluromethylarginine
      inhibited ethylene induced putrescine accumulation and coleoptile elongation. It
      seems that putrescine biosynthesis might be involved in the ethylene-induced
      elongation of rice coleoptiles.

PMID- 16652954
TI  - Lateral and Rotational Mobilities of Lipids in Specific Cellular Membranes of
      Eucalyptus gunnii Cultivars Exhibiting Different Freezing Tolerance.
AB  - Two cell lines of Eucalyptus gunnii have been shown to keep their differential
      frost tolerance at the cellular level after long-term culture. They have been
      used to investigate the fluidity of specific cell membranes in relation with
      frost tolerance. Protoplasts and isolated vacuoles were obtained from both cell
      lines. In addition, purified plasma membrane and tonoplast (the vacuolar
      membrane) were separated from a crude microsomal fraction through free-flow
      electrophoresis. The lateral and rotational mobilities of lipids in these
      different membranes were studied by two biophysical techniques: fluorescence
      recovery after photobleaching (FRAP) and fluorescence polarization. After
      labeling the vacuoles isolated from the frost-sensitive cells with 1-oleoyl-2-(7
      nitro-2,1,3-benz-oxadiazol-4-yl)aminocaproyl phosphatidylcholine, a single mobile
      component was observed with a diffusion coefficient of 2.4 x 10(-9) cm(2) s(-1)
      and a mobile fraction close to 100% at a temperature of 23 degrees C. When using
      isolated vacuoles from the frost tolerant line, a higher lateral diffusion of
      tonoplast lipids was found with a diffusion coefficient of 3.2 x 10(-9) cm(2) s(
      1), still with a mobile fraction close to 100%. No convincing data were obtained
      when performing fluorescence recovery after photobleaching experiments on
      protoplasts. Fluorescence polarization experiments confirmed the differential
      behavior of the two cell lines for tonoplast and also for plasma membrane. In
      addition, they showed that intrinsically tonoplast exhibited a higher fluidity
      than plasma membrane. Our results provide the first information on the fluidity
      of tonoplast and on the compared properties of two important plant membranes
      tonoplast and plasma membrane-through the use of two complementary biophysical
      approaches. In addition, they suggest there is a correlation between membrane
      fluidity and cold tolerance. The potential interest of plant vacuole as a natural
      model system in membrane studies is emphasized.

PMID- 16652955
TI  - Evidence for an Amiloride-Inhibited Mg/2H Antiporter in Lutoid (Vacuolar)
      Vesicles from Latex of Hevea brasiliensis.
AB  - Lutoids represent a lysosomal microvacuolar compartment of rubber-tree (Hevea
      brasiliensis) latex. We observed acidification of isolated vesicles after
      imposing an outward Mg(2+) diffusion gradient and dissipation of a preformed pH
      gradient in the presence of exogenous Mg(2+). These results suggest the presence
      of a Mg(2+)/H(+) antiporter. The maximum Mg(2+)/H(+) exchange rate was observed
      at pH 8.5. The K(m) values for Mg(2+) (2.6 mm) were identical for both influx and
      efflux experiments. When membrane potential was clamped at zero with K(+) and
      valinomycin, the response of the membrane potential probe oxonol VI showed that
      the Mg(2+)/H(+) exchange was electroneutral. Mg(2+)/H(+) exchange was inhibited
      by amiloride and imipramine. Both the inhibiting concentration range and the K(m)
      for Mg(2+) are similar to those reported for the Mg(2+)/2Na(+) antiporter in
      animals cell. These data are consistent with the existence of a Mg(2+)/2H(+)
      antiporter in a plant tonoplast.

PMID- 16652956
TI  - Spatial Distribution of Photosynthesis during Drought in Field-Grown and
      Acclimated and Nonacclimated Growth Chamber-Grown Cotton.
AB  - Inhomogeneous photosynthetic activity has been reported to occur in drought
      stressed leaves. In addition, it has been suggested that these water stress
      induced nonuniformities in photosynthesis are caused by "patchy" stomatal closure
      and that the phenomenon may have created the illusion of a nonstomatal component
      to the inhibition of photosynthesis. Because these earlier studies were performed
      with nonacclimated growth chamber-grown plants, we sought to determine whether
      such "patches" existed in drought-treated, field-grown plants or in chamber-grown
      plants that had been acclimated to low leaf water potentials (psi(leaf)). Cotton
      (Gossypium hirsutum L.) was grown in the field and subjected to drought by
      withholding irrigation and rain from 24 d after planting. The distribution of
      photosynthesis, which may reflect the stomatal aperture distribution in a
      heterobaric species such as cotton, was assayed by autoradiography after briefly
      exposing attached leaves of field-grown plants to (14)CO(2). A homogeneous
      distribution of radioactive photosynthate was evident even at the lowest
      psi(leaf) of -1.34 MPa. "Patchiness" could, however, be induced by uprooting the
      plant and allowing the shoot to air dry for 6 to 8 min. In parallel studies,
      growth chamber-grown plants were acclimated to drought by withholding irrigation
      for three 5-d drought cycles interspersed with irrigation. This drought
      acclimation lowered the psi(leaf) value at which control rates of photosynthesis
      could be sustained by approximately 0.7 MPa and was accompanied by a similar
      decline in the psi(leaf) at which patchiness first appeared. Photosynthetic
      inhomogeneities in chamber-grown plants that were visible during moderate water
      stress and ambient levels of CO(2) could be largely removed with elevated CO(2)
      levels (3000 muL L(-1)), suggesting that they were stomatal in nature. However,
      advanced dehydration (less than approximately 2.0 MPa) resulted in "patches" that
      could not be so removed and were probably caused by nonstomatal factors. The
      demonstration that patches do not exist in drought-treated, field-grown cotton
      and that the presence of patches in chamber-grown plants can be altered by
      treatments that cause an acclimation of photosynthesis leads us to conclude that
      spatial heterogeneities in photosynthesis probably do not occur frequently under
      natural drought conditions.

PMID- 16652957
TI  - Effects of the Air Pollutant SO(2) on Leaves : Inhibition of Sulfite Oxidation in
      the Apoplast by Ascorbate and of Apoplastic Peroxidase by Sulfite.
AB  - After SO(2) has entered leaves of spinach (Spinacia oleracea) through open
      stomata and been hydrated in the aqueous phase of cell walls, the sulfite formed
      can be oxidized to sulfate by an apoplastic peroxidase that is normally involved
      in phenol oxidation. The oxidation of sulfite is competitive with the oxidation
      of phenolics. During sulfite oxidation, the peroxidase is inhibited. In the
      absence of ascorbate, which is a normal constituent of the aqueous phase of the
      apoplast, peroxidative sulfite oxidation facilitates fast additional sulfite
      oxidation by a radical chain reaction. By scavenging radicals, ascorbate inhibits
      chain initiation and sulfite oxidation. Even after exposure of leaves to high
      concentrations of SO(2), which inhibited photosynthesis, the redox state of
      ascorbate remained almost unaltered in the apoplastic space of the leaves. It is
      concluded that the oxidative detoxification of SO(2) in the apoplast outside the
      cells is slow. Its rate depends on the rate of apoplastic hydrogen peroxide
      generation and on the steady-state apoplastic concentrations of phenolics and
      sulfite. The affinity of the peroxidase for phenolics is higher than that for
      sulfite.

PMID- 16652958
TI  - Synthesis and assembly of large subunits into ribulose bisphosphate
      carboxylase/oxygenase in chloroplast extracts.
AB  - We have developed a new system for the in vitro synthesis of large subunits and
      their assembly into ribulose bisphosphate carboxylase oxygenase (Rubisco)
      holoenzyme in extracts of higher plant chloroplasts. This differs from previously
      described Rubisco assembly systems because the translation of the large subunits
      occurs in chloroplast extracts as opposed to isolated intact chloroplasts, and
      the subsequent assembly of large subunits into holoenzyme is completely dependent
      upon added small subunits. Amino acid incorporation in this system displayed the
      characteristics previously reported for chloroplast-based translation systems.
      Incorporation was sensitive to chloramphenicol or RNase but resistant to
      cycloheximide, required magnesium, and was stimulated by nucleotides. The primary
      product of this system was the large subunit of Rubisco. However, several lower
      molecular weight polypeptides were formed. These were structurally related to the
      Rubisco large subunit. The initiation inhibitor aurintricarboxylic acid (ATA)
      decreased the amount of lower molecular weight products accumulated. The
      accumulation of completed large subunits was only marginally reduced in the
      presence of ATA. The incorporation of newly synthesized large subunits into
      Rubisco holoenzyme occurred under conditions previously identified as optimal for
      the assembly of in organello-synthesized large subunits and required the addition
      of purified small subunits.

PMID- 16652959
TI  - Prunus serotina Amygdalin Hydrolase and Prunasin Hydrolase : Purification, N
      Terminal Sequencing, and Antibody Production.
AB  - In black cherry (Prunus serotina Ehrh.) seed homogenates, amygdalin hydrolase
      (AH) participates with prunasin hydrolase (PH) and mandelonitrile lyase in the
      sequential degradation of (R)-amygdalin to HCN, benzaldehyde, and glucose. Four
      isozymes of AH (designated AH I, I', II, II') were purified from mature cherry
      seeds by concanavalin A-Sepharose 4B chromatography, ion-exchange chromatography,
      and chromatofocusing. All isozymes were monomeric glycoproteins with native
      molecular masses of 52 kD. They showed similar kinetic properties (pH optima,
      K(m), V(max)) but differed in their isoelectric points and N-terminal amino acid
      sequences. Analytical isoelectric focusing revealed the presence of subisozymes
      of each isozyme. The relative abundance of these isozymes and/or subisozymes
      varied from seed to seed. Three isozymes of PH (designated PH I, IIa, and IIb)
      were purified to apparent homogeneity by affinity, ion-exchange, and
      hydroxyapatite chromatography and by nondenaturing polyacrylamide gel
      electrophoresis. PH I and PH IIb are 68-kD monomeric glycoproteins, whereas PH
      IIa is dimeric (140 kD). The N-terminal sequences of all PH and AH isozymes
      showed considerable similarity. Polyclonal antisera raised in rabbits against
      deglycosylated AH I or a mixture of the three deglycosylated PH isozymes were not
      monospecific as judged by immunoblotting analysis, but also cross-reacted with
      the opposing glucosidase. Monospecific antisera deemed suitable for
      immunocytochemistry and screening of expression libraries were obtained by
      affinity chromatography. Each antiserum recognized all known isozymes of the
      specific glucosidase used as antigen.

PMID- 16652960
TI  - Tissue and Subcellular Localization of Enzymes Catabolizing (R)-Amygdalin in
      Mature Prunus serotina Seeds.
AB  - In black cherry (Prunus serotina Ehrh.) homogenates, (R)-amygdalin is catabolized
      to HCN, benzaldehyde, and d-glucose by the sequential action of amygdalin
      hydrolase, prunasin hydrolase, and mandelonitrile lyase. The tissue and
      subcellular localizations of these enzymes were determined within intact black
      cherry seeds by direct enzyme analysis, immunoblotting, and colloidal gold
      immunocytochemical techniques. Taken together, these procedures showed that the
      two beta-glucosidases are restricted to protein bodies of the procambium, which
      ramifies throughout the cotyledons. Although amygdalin hydrolase occurred within
      the majority of procambial cells, prunasin hydrolase was confined to the
      peripheral layers of this meristematic tissue. Highest levels of mandelonitrile
      lyase were observed in the protein bodies of the cotyledonary parenchyma cells,
      with lesser amounts in the procambial cell protein bodies. The residual endosperm
      tissue had insignificant levels of amygdalin hydrolase, prunasin hydrolase, and
      mandelonitrile lyase.

PMID- 16652961
TI  - Apoplastic expression of yeast-derived invertase in potato : effects on
      photosynthesis, leaf solute composition, water relations, and tuber composition.
AB  - In potato plants (Solanum tuberosum), a chimeric yeast-derived invertase gene
      fused to a 35S cauliflower mosaic virus promoter has been expressed. The protein
      was targeted to the cell wall by using the signal peptide of proteinase inhibitor
      II fused to the amino terminus of the yeast invertase. The transformed plants had
      crinkled leaves, showed a reduced growth rate, and produced fewer tubers.
      Although in the apoplast of the leaves of the transformed plants the content of
      glucose and fructose rose by a factor of 20, and that of sucrose declined 20
      fold, 98% of the carbohydrate in the phloem sap consisted of sucrose,
      demonstrating the strong specificity of phloem loading. In the leaf cells of the
      transformed plants, glucose, fructose, and amino acids, especially proline, were
      accumulated. Consequently, the osmolality of the cell sap rose from 250 to 350
      mosmol/kg. Our results show that the observed 75% decrease of photosynthesis is
      not caused by a feedback regulation of sucrose synthesis and is accompanied by an
      increase in the osmotic pressure in the leaf cells. In the transformed plants,
      not only the amino acid to sucrose ratio in the phloem sap, but also the amino
      acid and protein contents in the tubers were found to be elevated. In the tubers
      of the transformed plants, the protein to starch ratio increased.

PMID- 16652962
TI  - Operationally defined apoplastic and symplastic aluminum fractions in root tips
      of aluminum-intoxicated wheat.
AB  - Knowledge of the mechanistic basis of differential aluminum (Al) tolerance
      depends, in part, on an improved ability to quantify Al located in the apoplastic
      and symplastic compartments of the root apex. Using root tips excised from
      seedlings of an Al-tolerant wheat cultivar (Triticum aestivum L. cv Yecora Rojo)
      grown in Al solutions for 2 d, we established an operationally defined apoplastic
      Al fraction determined with six sequential 30-min washes using 5 mm CaCl(2) (pH
      4.3). Soluble symplastic Al was eluted by freezing root tips to rupture cell
      membranes and performing four additional 30-min CaCl(2) washes, and a residual
      fraction was determined via digestion of root tips with HNO(3). The three
      fractions were then determined in Yecora Rojo and a sensitive wheat cultivar
      (Tyler) grown at 18, 55, or 140 mum total solution Al (Al(T)). When grown at
      equal Al(T), Tyler contained more Al than Yecora Rojo in all fractions, but both
      total Al and fractional distribution were similar in the two cultivars grown at
      Al(T) levels effecting a 50% reduction in root growth. Residual Al was
      consistently 50 to 70% of the total, and its location was elucidated by staining
      root tips with the fluorophore morin and examining them using fluorescence and
      confocal laser scanning microscopy. Wall-associated Al was only observed in tips
      prior to any washing, and the residual fraction was manifested as distinct
      staining of the cytoplasm and nucleus but not of the apoplastic space.
      Accordingly, the residual fraction was allocated to the symplastic compartment
      for both cultivars, and recalculated apoplastic Al was consistently approximately
      30 to 40% of the total. Distributions of Al in the two cultivars did not support
      a symplastic detoxification hypothesis, but the role of cytoplasmic exclusion
      remains unsettled.

PMID- 16652963
TI  - In Vivo Competition between Plastocyanin and a Copper-Dependent Regulator of the
      Chlamydomonas reinhardtii Cytochrome c(6) Gene.
AB  - The Chlamydomonas reinhardtii gene encoding cytochrome c(6) (Cyt c(6)) is
      transcriptionally repressed by cupric ions. In quantitating the level of
      expression of this gene as a function of cupric ions available per cell, we find
      that transformed Chlamydomonas reinhardtii cells that accumulate high levels of
      plastocyanin (a type I copper protein) have a higher sensory threshold for copper
      dependent repression of the Cyt c(6) gene than do untransformed, otherwise
      isogenic, cells that are plastocyanin-deficient. Also, in wild-type cells, the
      extent to which the gene is expressed at any given ratio of copper/cell is
      exactly correlated with the predicted deficiency (at this level of copper) in the
      organism's capacity to synthesize holoplastocyanin. These results support a
      simple model in which the sensory threshold for transcriptional repression of the
      Cyt c(6) gene is determined by direct competition for intracellular copper ions
      between a copper-binding regulator of this gene and plastocyanin. Thus, the
      organism is able to maintain a constant amount of Cyt c(6) plus plastocyanin per
      Photosystem I. With the use of in vitro-generated Cyt c(6)-encoding transcripts
      as a standard for the quantitation of cellular Cyt c(6) mRNA levels, we estimate
      that whereas copper-deficient wild-type cells maintain approximately 1 x 10(2) to
      4 x 10(2) Cyt c(6)-specific transcripts per cell, copper-supplemented cells
      contain, on average, less than one Cyt c(6)-encoding mRNA. Thus, repression of
      the Cyt c(6) gene by copper ions is essentially 100%, making it unlikely that Cyt
      c(6) has any essential metabolic function in copper-supplemented cells. We find
      also that the steady-state levels of several transcripts, including those for Cyt
      c(6), are influenced by cell density, so that cells harvested at low density
      contain several-fold as many copies of a particular message as cells harvested
      near stationary phase.

PMID- 16652964
TI  - Characterization of an Electron Transport Pathway Associated with Glucose and
      Fructose Respiration in the Intact Chloroplasts of Chlamydomonas reinhardtii and
      Spinach.
AB  - The role of an electron transport pathway associated with aerobic carbohydrate
      degradation in isolated, intact chloroplasts was evaluated. This was accomplished
      by monitoring the evolution of (14)CO(2) from darkened spinach (Spinacia
      oleracea) and Chlamydomonas reinhardtii chloroplasts externally supplied with
      [(14)C]fructose and [(14)C]glucose, respectively, in the presence of nitrite,
      oxaloacetate, and conventional electron transport inhibitors. Addition of nitrite
      or oxaloacetate increased the release of (14)CO(2), but it was shown that O(2)
      continued to function as a terminal electron acceptor. (14)CO(2) evolution was
      inhibited up to 30 and 15% in Chlamydomonas and spinach, respectively, by 50 mum
      rotenone and by amytal, but at 500- to 1000-fold higher concentrations,
      indicating the involvement of a reduced nicotinamide adenine dinucleotide
      phosphate-plastoquinone oxidoreductase. (14)CO(2) release from the spinach
      chloroplast was inhibited 80% by 25 mum 2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone. (14)CO(2) release was sensitive to propylgallate, exhibiting
      approximately 50% inhibition in Chlamydomonas and in spinach chloroplasts of 100
      and 250 mum concentrations, respectively. These concentrations were 20- to 50
      fold lower than the concentrations of salicylhydroxamic acid (SHAM) required to
      produce an equivalent sensitivity. Antimycin A (100 mum) inhibited approximately
      80 to 90% of (14)CO(2) release from both types of chloroplast. At 75 mum, sodium
      azide inhibited (14)CO(2) evolution about 50% in Chlamydomonas and 30% in
      spinach. Sodium azide (100 mm) combined with antimycin A (100 mum) inhibited
      (14)CO(2) evolution more than 90%. (14)CO(2) release was unaffected by
      uncouplers. These results are interpreted as evidence for a respiratory electron
      transport pathway functioning in the darkened, isolated chloroplast. Chloroplast
      respiration defined as (14)CO(2) release from externally supplied [1
      (14)C]glucose can account for at least 10% of the total respiratory capacity
      (endogenous release of CO(2)) of the Chlamydomonas reinhardtii cell.

PMID- 16652965
TI  - Involvement of Molecular Oxygen in the Enzyme-Catalyzed NADH Oxidation and Ferric
      Leghemoglobin Reduction.
AB  - Ferric leghemoglobin reductase (FLbR) from soybean (Glycine max [L.] Merr)
      nodules catalyzed oxidation of NADH, reduction of ferric leghemoglobin (Lb(+3)),
      and reduction of dichloroindophenol (diaphorase activity). None of these
      reactions was detectable when O(2) was removed from the reaction system, but all
      were restored upon readdition of O(2). In the absence of exogenous electron
      carriers and in the presence of O(2) and excess NADH, FLbR catalyzed NADH
      oxidation with the generation of H(2)O(2) functioning as an NADH oxidase. The
      possible involvement of peroxide-like intermediates in the FLbR-catalyzed
      reactions was analyzed by measuring the effects of peroxidase and catalase on
      FLbR activities; both enzymes at low concentrations (about 2 mug/mL) stimulated
      the FLbR-catalyzed NADH oxidation and Lb(+3) reduction. The formation of H(2)O(2)
      during the FLbR-catalyzed NADH oxidation was confirmed using a sensitive assay
      based on the fluorescence emitted by dichlorofluorescin upon reaction with
      H(2)O(2). The stoichiometry ratios between the FLbR-catalyzed NADH oxidation and
      Lb(+3) reduction were not constant but changed with time and with concentrations
      of NADH and O(2) in the reaction solution, indicating that the reactions were not
      directly coupled and electrons from NADH oxidation were transferred to Lb(+3) by
      reaction intermediates. A study of the affinity of FLbR for O(2) showed that the
      enzyme required at least micromolar levels of dissolved O(2) for optimal
      activities. A mechanism for the FLbR-catalyzed reactions is proposed by analogy
      with related oxidoreductase systems.

PMID- 16652966
TI  - Purification of Two Superoxide Dismutase Isozymes and Their Subcellular
      Localization in Needles and Roots of Norway Spruce (Picea abies L.) Trees.
AB  - Two isozymes of superoxide dismutase (SOD; EC 1.15.1.1) were purified from Norway
      spruce (Picea abies L.) needles to apparent electrophoretic homogeneity.
      Purification factors were 354 for SOD I and 265 for SOD II. The native molecular
      mass of both purified enzymes was approximately 33 kD, as determined by gel
      filtration. The subunit molecular weights, as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, were 20,000 for SOD I and 16,000 for SOD II
      in the presence of 2-mercaptoethanol, and 15,800 and 15,000, respectively, in its
      absence. These results indicate that the native enzymes were homodimers whose
      subunits contained intrachain disulfide bonds. Isoelectric points determined by
      nondenaturing isoelectric focusing were 4.5 and 5.5 for SOD I and II,
      respectively. NH(2)-terminal sequence analysis of the first 22 to 23 amino acids
      revealed 70 to 75% sequence identity with chloroplastic CuZn SODs from other
      plant species for SOD I, and 75% sequence identity with the cytosolic CuZn SOD
      from Scots pine for SOD II. SOD I was the major activity in needles and it was
      associated with chloroplasts. SOD II activity was dominant in roots.

PMID- 16652967
TI  - Resistance Responses of Potato to Vesicular-Arbuscular Mycorrhizal Fungi under
      Varying Abiotic Phosphorus Levels.
AB  - In mycorrhizal symbioses, susceptibility of a host plant to infection by fungi is
      influenced by environmental factors, especially the availability of soil
      phosphorus. This study describes morphological and biochemical details of
      interactions between a vesicular-arbuscular mycorrhizal (VAM) fungus and potato
      (Solanum tuberosum L. cv Russet Burbank) plants, with a particular focus on the
      physiological basis for P-induced resistance of roots to infection. Root
      infection by the VAM fungus Glomus fasciculatum ([Thaxt. sensu Gerdemann]
      Gerdemann and Trappe) was extensive for plants grown with low abiotic P supply,
      and plant biomass accumulation was enhanced by the symbiosis. The capacity of
      excised roots from P-deficient plants to produce ethylene in the presence or
      absence of exogenous 1-amino cyclopropane-1-carboxylic acid (ACC) was markedly
      reduced by VAM infection. This apparent inhibition of ACC oxidase (ACC(ox))
      activity was localized to areas containing infected roots, as demonstrated in
      split-root studies. Furthermore, leachate from VAM roots contained a potent water
      soluble inhibitor of ethylene generation from exogenous ACC by nonmycorrhizal
      (NM) roots. The leachate from VAM-infected roots had a higher concentration of
      phenolics, relative to that from NM roots. Moreover, the rates of ethylene
      formation and phenolic concentration in leachates from VAM roots were inversely
      correlated, suggesting that this inhibitor may be of a phenolic nature. The
      specific activity of extracellular peroxidase recovered in root leachates was not
      stimulated by VAM infection, although activity on a fresh weight basis was
      significantly enhanced, reflecting the fact that VAM roots had higher protein
      content than NM roots. Polyphenol oxidase activity of roots did not differ
      between NM and VAM roots. These results characterize the low resistance response
      of P-deficient plants to VAM infection. When plants were grown with higher
      abiotic P supply, the relative benefit of the VAM symbiosis to plant growth
      decreased and root infection was lower. The in vivo ACC(ox) activity was also
      greater in roots of plants grown on high levels of P compared with those grown on
      low levels, although the influence of VAM infection was partially to counteract
      the nutritional effect of P on ACC(ox) activity. Similar to ACC(ox) activity,
      extracellular peroxidase activity of roots increased linearly with increasing
      abiotic P supply, thus indicating a greater potential for resistance to VAM
      infection. These findings suggest that VAM fungi may alter phenolic metabolism of
      roots so as to hinder ethylene production and the root's ability to invoke a
      defense response. Raising the abiotic P supply to plants at least partially
      restores the capacity of roots to produce ethylene and may, in this way, increase
      the root's resistance to VAM infection.

PMID- 16652968
TI  - Plant dihydroxyacetone phosphate reductases : purification, characterization, and
      localization.
AB  - A cytosolic form of dihydroxyacetone phosphate (DHAP) reductase was purified
      200,000-fold from spinach (Spinacia oleracea L.) leaves to apparent
      electrophoretic homogeneity. The purification procedure included anion-exchange
      chromatography, gel filtration, hydrophobic chromatography, and dye-ligand
      chromatography on Green-A and Red-A agaroses. The enzyme, prepared in an overall
      yield of 14%, had a final specific activity of about 500 mumol of DHAP reduced
      min(-1) mg(-1) protein, a subunit molecular mass of 38 kD, and a native molecular
      mass of 75 kD. A chloroplastic isoform of DHAP reductase was separated from the
      cytosolic form by anion-exchange chromatography and partially purified 56,000
      fold to a specific activity of 135 mumol min(-1) mg(-1) protein. Antibodies
      generated in rabbits against the cytosolic form did not cross-react with the
      chloroplastic isoform. The two reductases were specific for NADH and DHAP.
      Although they exhibited some dissimilarities, both isoforms were severely
      inhibited by higher molecular weight fatty acyl coenzyme A esters and
      phosphohydroxypyruvate and moderately inhibited by nucleotides. In contrast to
      previous reports, the partially purified chloroplastic enzyme was not stimulated
      by dithiothreitol or thioredoxin, nor was the purified cytosolic enzyme
      stimulated by fructose 2,6-bisphosphate. A third DHAP reductase isoform was
      isolated from spinach leaf peroxisomes that had been prepared by isopycnic
      sucrose density gradient centrifugation. The peroxisomal DHAP reductase was
      sensitive to antibodies raised against the cytosolic enzyme and had a slightly
      smaller subunit molecular weight than the cytosolic isoform.

PMID- 16652969
TI  - Bilevel disulfide group reduction in the activation of c(4) leaf nicotinamide
      adenine dinucleotide phosphate-malate dehydrogenase.
AB  - The time course of thioredoxin-mediated reductive activation of isolated Zea mays
      nicotinamide adenine dinucleotide phosphatemalate dehydrogenase is highly
      sigmoidal in nature. We examined the factors affecting these kinetics, including
      the thiol-disulfide status of unactivated and activated forms of the enzyme. The
      maximum steady rate of activation was increased, and the length of the lag in
      activation decreased, as the concentrations of thioredoxin-m, dithiothreitol, and
      KCl were increased. The lag in activation (sigmoidicity) was eliminated by
      preincubating the unactivated enzyme with 100 mm 2-mercaptoethanol; this
      pretreatment did not activate the enzyme. Unactivated nicotinamide adenine
      dinucleotide phosphate-malate dehydrogenase was found to contain approximately
      two SH groups per subunit, increasing to about four SH per subunit after
      pretreatment with 2-mercaptoethanol and six SH per subunit after activation by
      incubating the enzyme with dithiothreitol. We suggest that reduction of one
      particular higher redox potential disulfide group in unactivated nicotinamide
      adenine dinucleotide phosphate-malate dehydrogenase facilitates the subsequent
      reduction of the critical S-S group (regulatory S-S) necessary to generate the
      active form of the enzyme.

PMID- 16652970
TI  - Limitations of the pulse-modulated technique for measuring the fluorescence
      characteristics of algae.
AB  - Precise measurements of the minimal fluorescence yield (F(o)) and maximal
      fluorescence yield (F(m)) of a dark-adapted sample are prerequisites for the
      quantification of other fluorescence parameters. The pulse amplitude-modulated
      chlorophyll fluorometer (PAM 101 Chlorophyll Fluorometer, Heinz Walz, Effeltrich,
      Germany) and saturating pulse technique have frequently been used in measuring
      F(o) and F(m) and in resolving the contributions of photochemical and
      nonphotochemical quenching to the total fluorescence yield. The extent to which
      instrument-dependent factors may affect the accurate measurement of F(o) and F(m)
      is addressed. It is shown that the increase in pulse amplitude-modulated
      measuring beam intensity at 1.6 and 100 kHz was nonlinear at higher light
      intensity settings. The implications of this for measurements of F(o) (1.6 kHz)
      and F(m) (100 kHz) are discussed. It is also demonstrated that underestimation of
      F(m) may result due to saturation of the PAM 101 photodiode by scattered infrared
      light associated with intense light pulses. In addition, it is shown how sample
      dependent factors may affect measurements of F(o) and F(m) in samples with low
      chlorophyll concentrations, in particular, dilute algal suspensions of
      Phaeodactylum tricornutum and Chlamydomonas reinhardtii. A technique is presented
      for the accurate measurement of F(o) in algal suspensions (<8 mug chlorophyll a
      mL(-1)). The importance of examining the saturating pulse transient and F(m)
      level as a function of the damping setting, pulse width, and pulse intensity, and
      in the presence of 3-(3,4-dichlorophenyl)-1, 1-dimethylurea is discussed.

PMID- 16652971
TI  - Identification and expression of a cDNA clone encoding aspartate aminotransferase
      in carrot.
AB  - A full-length cDNA clone encoding aspartate aminotransferase (AAT) has been
      identified from a carrot root cDNA library. Degenerate oligo primers were
      synthesized from the known amino acid sequence of AAT form I from carrot (Daucus
      carota L. cv Danvers). These primers were utilized in a polymerase chain reaction
      to amplify a portion of a carrot AAT gene from first strand cDNA synthesized from
      poly(A)(+) RNA isolated from 5-d-old cell suspension cultures. The resulting 750
      bp fragment was cloned, mapped, and sequenced. The cloned fragment, mpAAT1, was
      used as a probe to identify a full-length cDNA clone in a library constructed
      from poly(A)(+) RNA isolated from carrot roots. A 1.52-kb full-length clone,
      AAT7, was isolated and sequenced. AAT7 has 54% nucleotide identity with both the
      mouse cytoplasmic and mitochondrial AAT genes. The deduced amino acid sequence
      has 52 and 53% identity with the deduced amino acid sequences of mouse
      cytoplasmic and mitochondrial AAT genes, respectively. Further analysis of the
      sequence data suggests that AAT7 encodes a cytoplasmic form of carrot AAT; the
      evidence includes the (a) absence of a transit or signal sequence, (b) lack of "m
      residues," or invariant mitochondrial residues, in the carrot AAT sequence, and
      (c) high degree of sequence similarity with the amino acid sequence previously
      obtained for form I of carrot, a cytoplasmic isoenzyme. High- and low-stringency
      hybridizations to Southern blots of carrot nuclear DNA with AAT7 show that AAT is
      part of a small multigene family. Northern blot analysis of AAT7 suggests that
      AAT is expressed throughout cell culture up to 7 d and is highly expressed in
      roots but not in leaves.

PMID- 16652972
TI  - Inactivation of maize leaf phosphoenolpyruvate carboxylase by the binding to
      chloroplast membranes.
AB  - Phosphoenolpyruvate carboxylase (PEPC) purified from maize (Zea mays L.) leaves
      associates with maize leaf chloroplast membrane in vitro. The binding of PEPC to
      the membrane results in enzyme inactivation. A protein isolated from a maize leaf
      chloroplast membrane preparation inactivated PEPC. Treatment with membrane
      preparation or with partially purified inactivating protein accelerates PEPC
      inactivation at low temperature (4 degrees C). Interaction of PEPC with
      chloroplast membrane or inactivating protein may inactivate the enzyme by
      influencing dissociation of the enzyme active tetramer.

PMID- 16652973
TI  - alpha-l-Arabinofuranosidase from Radish (Raphanus sativus L.) Seeds.
AB  - An alpha-l-arabinofuranosidase has been purified 1043-fold from radish (Raphanus
      sativus L.) seeds. The purified enzyme was a homogeneous glycoprotein consisting
      of a single polypeptide with an apparent molecular weight of 64,000 and an
      isoelectric point value of 4.7, as evidenced by denaturing gel electrophoresis
      and reversed-phase or size-exclusion high-performance liquid chromatography and
      isoelectric focusing. The enzyme characteristically catalyzes the hydrolysis of p
      nitrophenyl alpha-l-arabinofuranoside and p-nitrophenyl beta-d-xylopyranoside in
      a constant ratio (3:1) of the initial velocities at pH 4.5, whereas the
      corresponding alpha-l-arabinopyranoside and beta-d-xylofuranoside are
      unsusceptible. The following evidence was provided to support that a single
      enzyme with one catalytic site was responsible for the specificity: (a) high
      purity of the enzyme preparation, (b) an invariable ratio of the activities
      toward the two substrates throughout the purification steps, (c) a parallelism of
      the activities in activation with bovine serum albumin and in heat inactivation
      of the enzyme as well as in the inhibition with heavy metal ions and sugars such
      as Hg(2+), Ag(+), l-arabino-(1-->4)-lactone, and d-xylose, and (d) results of the
      mixed substrate kinetic analysis using the two substrates. The enzyme was shown
      to split off alpha-l-arabinofuranosyl residues in sugar beet arabinan, soybean
      arabinan-4-galactan, and radish seed and leaf arabinogalactan proteins. Arabinose
      and xylose were released by the action of the enzyme on oat-spelt xylan.
      Synergistic action of alpha-l-arabinofuranosidase and beta-d-galactosidase on
      radish seed arabinogalactan protein resulted in the extensive degradation of the
      carbohydrate moiety.

PMID- 16652974
TI  - Purification of an infection-related, extracellular peroxidase from barley.
AB  - Increases in two extracellular peroxidases were observed following inoculation of
      barley (Hordeum vulgare L.) with the powdery mildew pathogen (Erysiphe graminis
      DC.: Fr. f. sp. hordei Em. Marchal). The more prominent isozyme, P8.5, was
      purified from intercellular wash fluids by acetone precipitation, ion-exchange
      chromatography, isoelectric focusing, and gel filtration. Purified P8.5 is a heme
      containing, glycoprotein with a M(r) of 35,000. It has eight cysteine residues. A
      highly specific, high-titer antiserum to deglycosylated P8.5 was produced.

PMID- 16652975
TI  - Lactic Acid efflux as a mechanism of hypoxic acclimation of maize root tips to
      anoxia.
AB  - Hypoxic pretreatment (3 kPa oxygen) of maize (Zea mays L.) root tips improved
      their survival time in a subsequent anoxic incubation from 10 h to more than 3 d,
      provided that glucose was added to the medium to sustain metabolism. The
      glycolytic flux (lactate + ethanol) was the same in both pretreated and untreated
      root tips during the 1st h after transfer to anoxia. It was only after 2 h that
      it declined sharply in untreated tips, but was sustained in pretreated ones.
      Right after the transition from normoxia to anoxia of untreated root tips, the
      only fermentative product detected was lactic acid, which accumulated in a 7:1
      proportion after 30 min in tissue and medium, respectively. It took 10 min before
      ethanol could be detected and 20 min for it to be produced at its maximum rate at
      the expense of lactate production, which slowed down. In contrast, in hypoxically
      pretreated root tips, ethanol was produced at a maximum rate right after the
      transfer to anoxia. Concurrently, low amounts of lactic acid were produced that
      accumulated in a 1:1 proportion after 30 min in tissue and medium, respectively.
      This large efflux of lactic acid could account for the higher cytoplasmic pH
      values always found in pretreated tissues. The presence of cycloheximide during
      pretreatment abolished this difference, suggesting that the greater efficiency of
      lactate efflux was linked to protein synthesis. The role of lactate in cytosolic
      pH regulation and in sensitivity to anoxia is discussed.

PMID- 16652976
TI  - Gibberellin Is Required for Flowering in Arabidopsis thaliana under Short Days.
AB  - Mutants of Arabidopsis thaliana deficient in gibberellin synthesis (ga1-3 and ga1
      6), and a gibberellin-insensitive mutant (gai) were compared to the wild-type
      (WT) Landsberg erecta line for flowering time and leaf number when grown in
      either short days (SD) or continuous light (CL). The ga1-3 mutant, which is
      severely defective in ent-kaurene synthesis because it lacks most of the GA1
      gene, never flowered in SD unless treated with exogenous gibberellin. After a
      prolonged period of vegetative growth, this mutant eventually underwent
      senescence without having produced flower buds. The gai mutant and the "leaky"
      ga1-6 mutant did flower in SD, but took somewhat longer than WT. All the mutants
      flowered readily in CL, although the ga1-3 mutant showed some delay. Unlike WT
      and ga1-3, the gai mutant failed to respond to gibberellin treatment by
      accelerating flowering in SD. A cold treatment promoted flowering in the WT and
      gai, but failed to induce flowering in ga1-3. From these results, it appears that
      gibberellin normally plays a role in initiating flowering of Arabidopsis.

PMID- 16652977
TI  - Osmotin gene expression is posttranscriptionally regulated.
AB  - Accumulation of both osmotin mRNA and osmotin protein in tissues of tobacco
      (Nicotiana tabacum L. var Wisconsin 38) is subject to complex developmental
      control. Osmotin was found to be most abundant in tobacco roots and in tissues of
      the outer stem comprised primarily of epidermis, and it was less abundant in the
      corolla. It was a minor protein in other tissues and was undetectable in some
      tissues, including those of developing and mature seeds. The mRNA abundances did
      not always reflect the amount of protein accumulation because in some tissues
      high levels of mRNA but not protein were measured and vice versa. Accumulation of
      osmotin mRNA but not protein occurred in some plant tissues due to treatment with
      abscisic acid, wounding, and tobacco mosaic virus infection. Ethylene induced the
      accumulation of osmotin mRNA and, to a small extent, protein in seedlings, but
      was ineffective with cultured cells. Exposure of cultured cells and plants to
      NaCl caused high levels of both mRNA and the protein to accumulate. Thus, the
      accumulation of osmotin mRNA is controlled developmentally and by at least five
      hormonal or environmental signals. However, posttranscriptional processes can
      limit osmotin accumulation.

PMID- 16652978
TI  - Convergent Induction of Osmotic Stress-Responses : Abscisic Acid, Cytokinin, and
      the Effects of NaCl.
AB  - In Mesembryanthemum crystallinum, salt stress induces the accumulation of proline
      and a specific isoform of the enzyme phosphoenolpyruvate carboxylase (PEPCase)
      prior to the switch from C(3) to Crassulacean acid metabolism (CAM). To determine
      whether plant growth regulators initiate or imitate these responses, we have
      compared the effects elicited by NaCl, abscisic acid (ABA), and cytokinins using
      PEPCase and proline levels as diagnostic tools. Exogenously applied ABA is a poor
      substitute for NaCl in inducing proline and CAM-specific PEPCase accumulation.
      Even though ABA levels increase 8- to 10-fold in leaves during salt stress,
      inhibition of ABA accumulation does not affect these salt-induced responses. In
      contrast, the addition of cytokinins (6-benzylaminopurine, zeatin, 2
      isopentyladenine) mimic salt by greatly increasing proline and PEPCase amounts.
      Endogenous zeatin levels remain unchanged during salt stress. We conclude: (a)
      The salt-induced accumulation of proline and PEPCase is coincident with, but is
      not attributable to, the rise in ABA or zeatin concentration. (b) For the first
      time, cytokinins and NaCl are implicated as independent initiators of a sensing
      pathway that signals leaves to alter PEPCase gene expression. (c) During stress,
      the sensing of osmotic imbalances leading to ABA, proline, and CAM-specific
      PEPCase accumulation may be mediated directly by NaCl.

PMID- 16652979
TI  - Stress Tolerance of Photosystem II in Vivo: Antagonistic Effects of Water, Heat,
      and Photoinhibition Stresses.
AB  - The in vivo photochemical activity of photosystem II was inferred from modulated
      chlorophyll fluorescence and photoacoustic measurements in intact leaves of
      several plant species (Lycopersicon esculentum Mill., Solanum tuberosum L.,
      Solanum nigrum L.) exposed to various environmental stresses (drought, heat,
      strong light) applied separately or in combination. Photosystem II was shown to
      be highly drought-resistant: even a drastic desiccation in air of detached leaf
      samples only marginally affected the quantum yield for photochemistry in
      photosystem II. However, water stress markedly modified the responses of
      photosystem II to superimposed constraints. The stability of photosystem II to
      heat was observed to increase strongly in leaves exposed to water stress
      conditions: heat treatments (e.g. 42 degrees C in the dark), which caused a
      complete and irreversible inhibition of photosystem II in well-watered (tomato)
      leaves, resulted in a small and fully reversible reduction of the photochemical
      efficiency of photosystem II in drought-stressed leaves. In vivo photoacoustic
      data indicated that photosystem I was highly resistant to both heat and water
      stresses. When leaves were illuminated with intense white light at 25 degrees C,
      photoinhibition damage of photosystem II was more pronounced in water-stressed
      leaves than in undesiccated controls. However, in nondehydrated leaves,
      photoinhibition of photosystem II was strongly temperature dependent, being
      drastically stimulated at high temperatures above 38 to 40 degrees C. As a
      consequence, when exposed to strong light at high temperature, photosystem II
      photochemistry was significantly less inhibited in dehydrated leaves than in
      control well-hydrated leaves. Our results demonstrate the existence of a marked
      antagonism between physicochemical stresses, with water stress enhancing the
      resistance of photosystem II to constraints (heat, strong light at high
      temperature) that are usually associated with drought in the field.

PMID- 16652980
TI  - Expression, activity, and cellular accumulation of methyl jasmonate-responsive
      lipoxygenase in soybean seedlings.
AB  - Exposure of soybean (Glycine max) seedlings to low levels of atmospheric methyl
      jasmonate induced the expression and accumulation of one or more lipoxygenase(s)
      in the primary leaves, hypocotyls, epicotyls, and cotyledons. In the primary
      leaf, the major site of lipoxygenase accumulation in response to methyl jasmonate
      was in the vacuoles of paraveinal mesophyll cells. In the other organs, however,
      most of the methyl jasmonate-responsive lipoxygenase(s) were associated with both
      the epidermal and cortical cells and were present in both vacuoles and plastids.
      In plastids, the methyl jasmonate-responsive lipoxygenase was sequestered into
      protein inclusion bodies; no lipoxygenase was evident in either the thylakoids or
      the stroma. Both spectrophotometric measurement of conjugated diene formation and
      thin layer chromatography of lipoxygenase product formation indicated that methyl
      jasmonate caused an increase in the amount of lipoxygenase activity. Electron
      microscopy of the methyl jasmonate-responsive lipoxygenase protein in the
      vacuoles showed that it was arranged into a stellate, paracrystalline structure
      in various cell types other than the paraveinal mesophyll cells. The paracrystals
      appeared to be composed of tubular elements of between 5 and 8 nm in diameter,
      were of variable length, and were observed in most cell types of the seedling
      organs.

PMID- 16652981
TI  - Localized Changes in Flavonoid Biosynthesis in Roots of Lotus pedunculatus after
      Infection by Rhizobium loti.
AB  - Two-dimensional paper chromatography in four solvent systems, high-sensitivity
      spray reagents, and UV absorption spectroscopy were used to separate and
      characterize flavonoids and isoflavonoids in roots and root nodules of 20-d-old
      Lotus pedunculatus Cav. Seedlings were grown either under sterile conditions or
      after inoculation with Fix(+) or Fix(-) strains of Rhizobium loti. Flavonoids
      rather than isoflavonoids predominated in all tissues. Flavonoid profiles in
      sterile and denodulated root tissues were remarkably similar, both qualitatively
      and quantitatively. At least 14 partially purified flavonoid aglycones and
      conjugates were found in root extracts; denodulated root tissues contained no
      compounds that were not also present in sterile roots. Fix(+) rhizobia were
      responsible for major postinfection shifts in plant flavonoid biosynthesis at the
      sites of nodule morphogenesis. Polymeric flavolans were absent from Fix(+)
      nodules but present in all root tissues and in Fix(-) nodules. Catechin was
      detected only in Fix(+) nodules.

PMID- 16652982
TI  - Short-term effects of rhizosphere microorganisms on fe uptake from microbial
      siderophores by maize and oat.
AB  - Effects of rhizosphere microorganisms on Fe uptake by oat (Avena sativa) and
      maize (Zea mays) were studied in short-term (10 h) nutrient solution experiments.
      Fe was supplied either as microbial siderophores (pseudobactin [PSB] or
      ferrioxamine B [FOB]) or as phytosiderophores obtained as root exudates from
      barley (epi-3-hydroxy-mugineic acid [HMA]) under varied population densities of
      rhizosphere microorganisms (axenic, uninoculated, or inoculated with different
      microorganism cultures). When maize was grown under axenic conditions and
      supplied with FeHMA, Fe uptake rates were 100 to 300 times higher compared to
      those in plants supplied with Fe siderophores. Fe from both sources was taken up
      without the involvement of an extracellular reduction process. The supply of
      FeHMA enhanced both uptake rate and translocation rate to the shoot (more than
      60% of the total uptake). However, increased density of microorganisms resulted
      in a decrease in Fe uptake rate (up to 65%), presumably due to microbial
      degradation of the FeHMA. In contrast, when FeFOB or FePSB was used as the Fe
      source, increased population density of microorganisms enhanced Fe uptake. The
      enhancement of Fe uptake resulted from the uptake of FeFOB and FePSB by
      microorganisms adhering to the rhizoplane or living in the free space of cortical
      cells. The microbial apoplastic Fe pool was not available for root to shoot
      transport or, thus, for utilization by the plants. These results, in addition to
      the low uptake rate under axenic conditions, are in contrast to earlier
      hypotheses suggesting the existence of a specific uptake system for Fe
      siderophores in higher plants. The bacterial siderophores PSB and FOB were
      inefficient as Fe sources for plants even when supplied by stem injection. It was
      concluded that microorganisms are involved in degradation processes of microbial
      siderophores, as well as in competition for Fe with higher plants.

PMID- 16652983
TI  - Partial purification and properties of an inducible uridine 5'-diphosphate
      glucose-salicylic Acid glucosyltransferase from oat roots.
AB  - A salicylic acid (SA)-inducible uridine 5'-diphosphate (UDP)-glucose:SA 3-O
      glucosyltransferase was extracted from oat (Avena sativa L. cv Dal) roots.
      Reverse phase high-performance liquid chromatography or anion exchange
      chromatography was used to separate SA from the product, beta-O-d
      glucosylsalicylic acid. The soluble enzyme was purified 176-fold with 5% recovery
      using a combination of pH fractionation, anion exchange, gel filtration, and
      chromatofocusing chromatography. The partially purified protein had a native
      molecular weight of about 50,000, an apparent isoelectric point at pH 5.0, and
      maximum activity at pH 5.5. The enzyme had a K(m) of 0.28 mm for UDP-glucose and
      was highly specific for this sugar donor. More than 20 hydroxybenzoic and
      hydroxycinnamic acid derivatives were assayed as potential glucose acceptors. UDP
      glucose:SA 3-O-glucosyltransferase activity was highly specific toward SA (K(m) =
      0.16 mm). The enzyme was inhibited by UDP and uridine 5'-triphosphate but not by
      up to 7.5 mm uridine 5'-monophosphate.

PMID- 16652984
TI  - Bronze-2 Gene Expression and Intron Splicing Patterns in Cells and Tissues of Zea
      mays L.
AB  - A large fraction of the transcripts of the Bronze-2 (Bz2) gene of maize (Zea mays
      L.) are unspliced in purple husk tissues. The accumulation of unspliced messages
      could have destructive potential if the intron-bearing mRNAs are translated into
      aberrant proteins. Our initial studies suggested that both genetic and
      physiological factors may influence the degree of splicing failure. Nuclear
      background rather than cis-sequence effects is shown to contribute to the genetic
      component. The accumulation of unspliced message does not appear to be directly
      influenced by diurnal effects on transcript abundance, by the expression level of
      the Bz2 gene, or by thermal stress. We also show that maize cell cultures (Black
      Mexican Sweet, BMS) can be used to examine the molecular details involved in
      splicing failure. Much like whole maize plants, the BMS cells excise the Bz2
      intron with varying degrees of efficiency. In contrast with heterologous
      constructs containing plant introns, splicing of the native Bz2 intron can
      appproach 100% in BMS cells. Splicing of transcripts from a marked, introduced
      gene can be compared to the endogeneous Bz2 gene facilitating analysis of the
      impact of sequence changes.

PMID- 16652985
TI  - Improvement of Longevity and Viability of Sperm Cells Isolated from Pollen of Zea
      mays L.
AB  - Our previous studies showed that the common maize (Zea mays L.) sperm isolation
      medium (Brewbaker and Kwack salts in 0.44 m sucrose without buffering) caused
      cell lysis in vitro. In an attempt to remedy this situation, 6 sugars, 10
      buffers, 5 pH values, and 3 membrane protective agents were screened to improve
      longevity and viability of isolated Zea mays sperm cells as estimated by
      hemacytometry and flow cytometry. Use of 0.55 m galactose in the isolation
      solution increased sperm yield by 2.5-fold compared with sucrose, and suspension
      of isolated sperm cells in the galactose solution gave the best longevity among
      the six sugars. Buffering the galactose solution with 2 mm 2-(N
      morpholino)ethanesulfonic acid significantly improved longevity, whereas other
      buffers had no effect or decreased the longevity and/or viability. Among the five
      pH values tested (5.0, 6.0, 6.7, 7.0, and 8.0), pH 6.7 appeared to be optimal for
      maintenance of both longevity and viability. Screening of membrane protectants
      showed that cysteine caused a rapid decrease in cell viability and increased
      lysis, whereas dithiothreitol increased the cell numbers but lowered their
      viability. Addition of 0.1% bovine serum albumin increased cell numbers and
      viability, and about 70% of the cells remained viable after 72 h of suspension.
      Cell longevity and viability were also improved in 0.44 m sucrose when the
      solution was conditioned with 2-(N-morpholino)ethanesulfonic acid and bovine
      serum albumin. Use of 2-(N-morpholino)ethanesulfonic acid and bovine serum
      albumin inthe isolation and suspension medium significantly improved the
      viability and longevity of sperm cells isolated from Zea mays pollen.

PMID- 16652986
TI  - In situ incorporation of Fatty acids into lipids of the outer and inner envelope
      membranes of pea chloroplasts.
AB  - When incubated with [1-(14)C]acetate and cofactors (ATP, Coenzyme A, sn-glycerol
      3-phosphate, UDPgalactose, and NADH), intact chloroplasts synthesized fatty acids
      that were subsequently incorporated into most of the lipid classes. To study
      lipid synthesis at the chloroplast envelope membrane level, (14)C-labeled pea
      (Pisum sativum) chloroplasts were subfractionated using a single flotation
      gradient. The different envelope membrane fractions were characterized by their
      density, lipid and polypeptide composition, and the localization of enzymic
      activities (UDPgalactose-1,2 diacylglycerol galactosyltransferase, Mg(2+)
      dependent ATPase). They were identified as very pure outer membranes (light
      fraction) and strongly enriched inner membranes (heavy fraction). A fraction of
      intermediate density, which probably contained double membranes, was also
      isolated. Labeled glycerolipids recovered in the inner envelope membrane were
      phosphatidic acid, phosphatidyl-glycerol, 1,2 diacylglycerol, and
      monogalactosyldiacylglycerol. Their (14)C-fatty acid composition indicated that a
      biosynthetic pathway similar to the prokaryotic pathway present in cyanobacteria
      occurred in the inner membrane. In the outer membrane, phosphatidylcholine was
      the most labeled glycerolipid. Phosphatidic acid, phosphatidylglycerol, 1,2
      diacylglycerol, and monogalactosyldiacylglycerol were also labeled. The (14)C
      fatty acid composition of these lipids showed a higher proportion of oleate than
      palmitate. This labeling, different from that of the inner membrane, could result
      either from transacylation activities or from a biosynthetic pathway not yet
      described in pea and occurring partly in the outer chloroplast envelope membrane.
      This metabolism would work on an oleate-rich pool of fatty acids, possibly due to
      the export of oleate from chloroplast toward the extrachloroplastic medium. The
      respective roles of each membrane for chloroplast lipid synthesis are emphasized.

PMID- 16652987
TI  - Comparison of Pch313 (pTOM13 Homolog) RNA Accumulation during Fruit Softening and
      Wounding of Two Phenotypically Different Peach Cultivars.
AB  - Pch313 was isolated as a cDNA whose RNA accumulated during the softening period
      of peach (Prunus persica L. Batsch) fruit development. To better understand the
      role of the gene, we compared the amount of pch313-related RNA detected during
      fruit softening and tissue wounding between cultivars with different softening
      characteristics. The cultivar that softened faster, "Bailey," had a significantly
      higher amount of pch313-related RNA accumulate during softening than the slower
      softening cultivar, "Suncrest." Pch313 was sequenced and found to be related to a
      tomato fruit cDNA clone, pTOM13, which has been shown to encode the ethylene
      forming enzyme. The derived amino acid sequence of pch313 is 74 to 83% identical
      to the pTOM13-related sequences. A pch313-3' noncoding region probe was used to
      demonstrate that pch313 is related to both a wound-induced RNA transcript and the
      major fruit-softening transcript. The relationship of pch313 RNA accumulation and
      ethylene evolution was examined upon wounding and appeared to be both tissue and
      cultivar specific. When leaves were wounded, more pch313-related RNA was detected
      in Bailey and the rate of ethylene evolved was also higher in Bailey. When fruits
      were wounded, the levels of ethylene evolved were nearly identical but Suncrest
      accumulated more pch313-related RNA. Southern analysis of the DNA indicated a
      small number of related genes.

PMID- 16652988
TI  - Molecular characterization of the soybean alcohol dehydrogenase gene family
      amplified in vitro by the polymerase chain reaction.
AB  - Soybean (Glycine max) alcohol dehydrogenase (ADH) cDNAs were amplified in vitro
      from total RNA by the polymerase chain reaction (PCR). The amplification strategy
      involved first strand cDNA synthesis from anaerobic cotyledon total RNA using an
      18-thymidine primer. The second strand cDNA primer was a conserved sequence near
      the 5' end of known plant ADH transcripts. The PCR products were ligated into a
      plasmid vector and unique clones were isolated on the basis of size and
      restriction pattern. Sequence analysis revealed three distinct classes of soybean
      ADH cDNAs, all of which showed high homology to Adh genes from maize and peas.
      RNA blot hybridization analyses showed differential expression patterns for these
      genes. One gene, expressed constitutively in all seedling organs, was inducible
      by anaerobiosis, one gene was expressed only in anaerobic organs, and the third
      gene was expressed predominantly in anaerobic roots.

PMID- 16652989
TI  - Surface chemical properties of purified root cell walls from two tobacco
      genotypes exhibiting different tolerance to manganese toxicity.
AB  - Surface chemical characteristics of root cell walls extracted from two tobacco
      genotypes exhibiting differential tolerance to Mn toxicity were studied using
      potentiometric pH titration and Fourier transform infrared spectroscopy. The Mn
      sensitive genotype KY 14 showed a stronger interaction of its cell wall surface
      with metal ions than did the Mn-tolerant genotype Tobacco Introduction (T.I.)
      1112. This observation may be attributed to the relatively higher ratio of COO(-)
      to COOH in KY 14 cell walls than that found in the cell walls of T.I. 1112 in the
      pH range of 4 to 10. For both genotypes, the strength of binding between metal
      ions and cell wall surface was in the order of Cu > Ca > Mn > Mg > Na. However, a
      slightly higher preference of Ca over Mn was observed with the T.I. 1112 cell
      wall. This may explain the high accumulation of Mn in the leaves of Mn-tolerant
      genotype T.I. 1112 rather than the high accumulation of Mn in roots, as occurred
      in Mn-sensitive KY 14. It is concluded that surface chemical characteristics of
      cell walls may play an important role in plant metal ion uptake and tolerance.

PMID- 16652990
TI  - Sucrose phosphate synthase and sucrose accumulation at low temperature.
AB  - The influence of growth temperature on the free sugar and sucrose phosphate
      synthase content and activity of spinach (Spinacia oleracea) leaf tissue was
      studied. When plants were grown at 25 degrees C for 3 weeks and then transferred
      to a constant 5 degrees C, sucrose, glucose, and fructose accumulated to high
      levels during a 14-d period. Predawn sugar levels increased from 14- to 20-fold
      over the levels present at the outset of the low-temperature treatment. Sucrose
      was the most abundant free sugar before, during, and after exposure to 5 degrees
      C. Leaf sucrose phosphate synthase activity was significantly increased by the
      low-temperature treatment, whereas sucrose synthase and invertases were not.
      Synthesis of the sucrose phosphate synthase subunit was increased during and
      after low-temperature exposure and paralleled an increase in the steady-state
      level of the subunit. The increases in sucrose and its primary biosynthetic
      enzyme, sucrose phosphate synthase, are discussed in relation to adjustment of
      metabolism to low nonfreezing temperature and freezing stress tolerance.

PMID- 16652991
TI  - Auxin Biosynthesis during Seed Germination in Phaseolus vulgaris.
AB  - The relative roles of de novo biosynthesis of indoleacetic acid (IAA) and IAA
      conjugates stored in mature seeds (Phaseolus vulgaris L.) in supplying auxin to
      germinating bean seedlings were studied. Using (2)H oxide and 2,4,5,6,7-[(2)H]l
      tryptophan as tracers of IAA synthesis, we have shown that de novo biosynthesis
      of IAA, primarily from tryptophan, is an important source of auxin for young bean
      seedlings. New synthesis of IAA was detected as early as the second day of
      germination, at which time the seedlings began to accumulate fresh weight
      intensively and the total content of free IAA began to increase steadily. IAA
      conjugates that accumulate in large amounts in cotyledons of mature seeds may
      thus be considered to be only one of the possible sources of IAA required for the
      growth of bean seedlings.

PMID- 16652992
TI  - Hydrogen Photoevolution Indicates an Increase in the Antenna Size of Photosystem
      I in Chlamydobotrys stellata during Transition from Autotrophic to
      Photoheterotrophic Nutrition.
AB  - The changes in the light-harvesting antenna size of photosystem I were
      investigated in the green alga Chlamydobotrys stellata during transition from
      autotrophic to photoheterotrophic nutrition by measuring the light-saturation
      behavior of hydrogen evolution following single turnover flashes. It was found
      that during autotrophic-to-photoheterotrophic transition the antenna size of
      photosystem I increased from 180 to 250 chlorophyll. The chlorophyll (a + b)/P700
      ratio decreased from 800 to 550. The electron transport of photosystem I measured
      from reduced 2,6-dichloro-phenolindophenol to methylviologen was accelerated 1.4
      times. In the 77K fluorescence spectra, the photosystem II fluorescence yield was
      considerably lowered relative to the photosystem I fluorescence yield. It is
      suggested that the increased light-harvesting capacity and redistribution of
      absorbed excitation energy in favor of photosystem I is a response of
      photoheterotrophic algae to meet the ATP demand for acetate metabolism by
      efficient photosystem I cyclic electron transport when the noncyclic
      photophosphorylation is inhibited by CO(2) deficiency.

PMID- 16652993
TI  - Induction of Glutamine Synthetase Activity in Nonnodulated Roots of Glycine max,
      Phaseolus vulgaris, and Pisum sativum.
AB  - Nitrate or ammonium fertilization significantly increased glutamine synthetase
      (GS) activity in nonnodulated roots of French bean (Phaseolus vulgaris), soybean
      (Glycine max), and pea (Pisum sativum). Western analysis revealed substantial GS
      antibody-positive protein in root extracts that had minimal GS activity,
      indicating that an inactive form of GS may be present in nonfertilized plants.

PMID- 16652994
TI  - A new method of measuring protein-methionine-s-oxide reductase activity.
AB  - A new assay for measuring protein-methionine-S-oxide reductase is reported. The
      assay measures the conversion of N-(9-fluorenylmethoxycarbonyl)-methionine
      sulfoxide to N-(9-fluorenylmethoxycarbonyl)-methionine using fluorescence
      detection after high-performance liquid chromatography separation. Enzyme
      activity is linear over a 60-min period and the assay is sensitive enough to
      detect the consumption of only 1% of available substrate. Protein-methionine-S
      oxide reductase activity was demonstrated in pea (Pisum sativum L.) chloroplasts,
      and enzyme levels in leaves of etiolated and light-grown seedlings were compared.

PMID- 16652995
TI  - The Primary Structure of a cDNA Clone of the Stearoyl-Acyl Carrier Protein
      Desaturase Gene from Potato (Solanum tuberosum L.).

PMID- 16652996
TI  - Nucleotide sequence of a cDNA encoding the ethylene-forming enzyme from petunia
      corollas.

PMID- 16652997
TI  - Nucleotide Sequence of a Root-Specific Transcript Encoding a Germin-Like Protein
      from the Halophyte Mesembryanthemum crystallinum.

PMID- 16652998
TI  - Molecular cloning and sequence analysis of an andean potato mottle virus cDNA
      clone encoding the major coat protein.

PMID- 16652999
TI  - The Uptake of (+)-S- and (-)-R-Abscisic Acid by Suspension Culture Cells of
      Hopbush (Dodonaea viscosa).
AB  - The uptake of (+)-S- and (-)-R-abscisic acid (ABA) by suspension culture cells of
      hopbush (Dodonaea viscosa L. Jacqu.) was followed over a range of temperatures,
      pH values, and time intervals. The natural (+)-S-ABA was taken up about five
      times faster than the unnatural (-)-R-ABA. Each 10 degrees C rise in temperature
      from 1 to 31 degrees C increased the rate of uptake (Q(10)) of (+)-S-ABA about
      2.2-fold, whereas that of the (-)-R increased with a Q(10) of 1.4. (+)-ABA was
      taken into the cells by a saturable carrier, but (-)-ABA and both enantiomers of
      2-trans-ABA were not; they appeared to enter by passive diffusion. The uptake of
      (+)-ABA was linear over the first 8 hours but concentrations within the cells
      decreased after 2 hours to remain constant after 4 hours as rapid metabolism was
      induced. Electron microscopy of thin sections of the cells, combined with a
      stereological analysis of their shape, showed that the vacuoles comprised 80% of
      the cell volume and the cytoplasm plus nucleus comprised 20%. There were no
      photosynthetically active plastids in the cells. Concentrations of the endogenous
      ABA in the cytoplasm (pH 7.32) and vacuoles (pH 5.88) were calculated by applying
      the Henderson-Hasselbalch equation (ABA pK(a) 4.7) so that, provided no active
      metabolic redistribution occurred, the concentration in the cytoplasm was 7.9
      micromolar and that in the vacuole was 0.3 micromolar. In vivo pH was measured by
      (31)P nuclear magnetic resonance spectroscopy.

PMID- 16653000
TI  - Nucleotide Sequence of Cauliflower Mosaic Virus Isolate NY8153.

PMID- 16653001
TI  - Analysis of Indole-3-Acetic Acid Metabolites from Dalbergia dolichopetala by High
      Performance Liquid Chromatography-Mass Spectrometry.
AB  - A mixture of [2-(14)C(1)] and [(13)C(6)]indole-3-acetic acid was applied to the
      cotyledons of 6-day-germinated seeds of "jacaranda do cerrado" (Dalbergia
      dolichopetala) and after 8 hours the seeds were extracted. Analysis of the
      fractionated extract by reversed-phase high performance liquid chromatography
      radiocounting revealed the presence of five radiolabeled metabolite peaks (I-V).
      After further purification, the individual peaks of radioactivity were analyzed
      by combined high performance liquid chromatography-steel filter-fast atom
      bombardment-mass spectrometry. The metabolite fraction V was found to contain
      [(14)C(1), (13)C(6)]indole-3-acetylas-partic acid and unlabeled indole-3
      acetylglutamic acid. Analysis of the metabolite fraction II revealed the presence
      of dioxindole-3-acetylaspartic acid and putative dioxindole-3-acetylglutamic acid
      as well as putative benzene ring-hydroxylated derivatives of oxindole-3
      acetylaspartic acid and oxindole-3-acetylglutamic acid. There was no evidence of
      significant incorporation of label from [2'-(14)C(1)] or [(13)C(6)]indole-3
      acetic acid into any of these conjugated indoles.

PMID- 16653002
TI  - NAD-Linked Isocitrate Dehydrogenase: Isolation, Purification, and
      Characterization of the Protein from Pea Mitochondria.
AB  - The NAD(+)-dependent isocitrate dehydrogenase from etiolated pea (Pisum sativum
      L.) mitochondria was purified more than 200-fold by dye-ligand binding on Matrix
      Gel Blue A and gel filtration on Superose 6. The enzyme was stabilized during
      purification by the inclusion of 20% glycerol. In crude matrix extracts, the
      enzyme activity eluted from Superose 6 with apparent molecular masses of 1400 +/-
      200, 690 +/- 90, and 300 +/- 50 kD. During subsequent purification steps the
      larger molecular mass species disappeared and an additional peak at 94 +/- 16 kD
      was evident. The monomer for the enzyme was tentatively identified at 47 kD by
      sodium dodecyl-polyacrylamide gel electrophoresis. The NADP(+)-specific
      isocitrate dehydrogenase activity from mitochondria eluted from Superose 6 at 80
      +/- 10 kD. About half of the NAD(+) and NADP(+)-specific enzymes remained bound
      to the mitochondrial membranes and was not removed by washing. The NAD(+)
      dependent isocitrate dehydrogenase showed sigmodial kinetics in response to
      isocitrate (S(0.5) = 0.3 mm). When the enzyme was aged at 4 degrees C or frozen,
      the isocitrate response showed less allosterism, but this was partially reversed
      by the addition of citrate to the reaction medium. The NAD(+) isocitrate
      dehydrogenase showed standard Michaelis-Menten kinetics toward NAD(+) (K(m) = 0.2
      mm). NADH was a competitive inhibitor (K(i) = 0.2 mm) and, unexpectedly, NADPH
      was a noncompetitive inhibitor (K(i) = 0.3 mm). The regulation by NADPH may
      provide a mechanism for coordination of pyridine nucleotide pools in the
      mitochondria.

PMID- 16653003
TI  - Nitrate activation of cytosolic protein kinases diverts photosynthetic carbon
      from sucrose to amino Acid biosynthesis: basis for a new concept.
AB  - The regulation of carbon partitioning between carbohydrates (principally sucrose)
      and amino acids has been only poorly characterized in higher plants. The
      hypothesis that the pathway of sucrose and amino acid biosynthesis compete for
      carbon skeletons and energy is widely accepted. In this review, we suggest a
      mechanism involving the regulation of cytosolic protein kinases whereby the flow
      of carbon is regulated at the level of partitioning between the pathways of
      carbohydrate and nitrogen metabolism via the covalent modulation of component
      enzymes. The addition of nitrate to wheat seedlings (Triticum aestivum) grown in
      the absence of exogenous nitrogen has a dramatic, if transient, impact on sucrose
      formation and on the activities of sucrose phosphate synthase (which is
      inactivated) and phosphoenolpyruvate carboxylase (which is activated). The
      activities of these two enzymes are modulated by protein phosphorylation in
      response to the addition of nitrate, but they respond in an inverse fashion.
      Sucrose phosphate synthase in inactivated and phosphoenolpyruvate carboxylase is
      activated. Nitrate functions as a signal metabolite activating the cytosolic
      protein kinase, thereby modulating the activities of at least two of the key
      enzymes in assimilate partitioning and redirecting the flow of carbon away from
      sucrose biosynthesis toward amino acid synthesis.

PMID- 16653004
TI  - Biosynthesis of White Lupin Isoflavonoids from [U-C]l-Phenylalanine and Their
      Release into the Culture Medium.
AB  - Pulse-labeling experiments of white lupin (Lupinus albus L.) cell cultures with
      [U-(14)C]l-phenylalanine for 72 h resulted in the incorporation of the
      radioactivity into the isoflavone aglucones, glucosides, and prenylated
      derivatives. Both the aglucones genistein and 2'-hydroxygenistein and their 7-O
      glucosides accounted for 85% of the total isoflavonoids identified in the
      cultured cells and contained 35% of the radioactivity, whereas the prenylated
      derivatives comprised 15 and 65%, respectively. Almost 20% of the labeled
      isoflavones of the cellular pool was recovered from the culture medium, 90% of
      which were monoprenylated and diprenylated derivatives containing 80% of the
      radioactivity. These results clearly demonstrate the release into the culture
      medium of a substantial amount of the endogenously synthesized isoflavonoids,
      especially the prenylated derivatives.

PMID- 16653005
TI  - Developmental change in c(6)-aldehyde formation by soybean leaves.
AB  - Damage to plant leaves by wounding or freezing induces the production of large
      amounts of C(6)-compounds. However, the control of formation of these compounds
      in leaves is not yet clear. In the current study, C(6)-aldehyde formation by
      freeze-injured soybean leaves of different ages (based on the leaf positions on
      the plant) at stage R1 of plant development was investigated. The results
      demonstrate that C(6)-aldehyde formation by the soybean (Glycine max L.) leaves
      changes as leaves develop. Younger leaves produce high levels of C(6)-aldehydes,
      mainly composed of hexanal. Subsequently, as the leaves develop, the level of
      C(6)-aldehyde formation decreases markedly, followed by an increase with a large
      shift from hexanal to hexenals. Lipoxygenase and lipolytic acyl hydrolase
      activity was reduced, and, in contrast, hydroperoxide lyase activity increased.
      There was little difference in lipoxygenase substrate specificity for linoleic
      acid and linolenic acid, but hydroperoxide lyase preferentially utilized 13
      hydroperoxy-9,11,15-octadecatrienoic acid. In the in vivo lipoxygenase substrate
      pool, the linoleic acid level declined and the relative level of linolenic acid
      increased. The change in ratios of linolenic acid to linoleic acid showed a
      similar trend during soybean leaf development to that of hexenals to hexanal.

PMID- 16653006
TI  - Seed effects on gibberellin metabolism in pea pericarp.
AB  - Pea fruit (Pisum sativum L.) is a model system for studying the effect of seeds
      on fruit growth in order to understand coordination of organ development. The
      metabolism of (14)C-labeled gibberellin A(12) (GA(12)) by pea pericarp was
      followed using a method that allows access to the seeds while maintaining
      pericarp growth in situ. Identification and quantitation of GAs in pea pericarp
      was accomplished by combined gas chromatography-mass spectrometry following
      extensive purification of the putative GAs. Here we report for the first time
      that the metabolism of [(14)C]GA(12) to [(14)C]GA(19) and [(14)C]GA(20) occurs in
      pericarp of seeded pea fruit. Removal of seeds from the pericarp inhibited the
      conversion of radiolabeled GA(19) to GA(20) and caused the accumulation of
      radiolabeled and endogenous GA(19). Deseeded pericarp contained no detectable
      GA(20), GA(1), or GA(8), whereas pericarp with seeds contained endogenous and
      radiolabeled GA(20) and endogenous GA(1). These data strongly suggest that seeds
      are required for normal GA biosynthesis in the pericarp, specifically the
      conversion of GA(19) to GA(20).

PMID- 16653007
TI  - Ethylene is not involved in the blue light-induced growth inhibition of red light
      grown peas.
AB  - Although the growth of intact plants is inhibited by irradiation with blue light,
      the growth rate of isolated stem segments is largely unaffected by blue light. We
      hypothesized that this loss of responsiveness was a result of ethylene production
      as part of the wounding response. However, we found no interaction between
      ethylene- and blue light-induced growth inhibition in dark- or red light-grown
      seedlings of pea (Pisum sativum L.). Inhibition of growth begins in dark-grown
      seedlings exposed to blue light within 3 min of the onset of blue light, as was
      known for red light-grown seedlings. By contrast, ethylene-induced inhibition of
      growth occurs only after a lag of 20 to 30 min or more (dark-grown seedlings) or
      60 min (red light-grown seedlings). Also, the inhibition response of red light
      grown seedlings is the same whether ethylene is present from the onset of
      continuous blue-light treatment or not. Finally the spatial distribution of
      inhibition following blue light was different from that following ethylene
      treatment.

PMID- 16653008
TI  - Purification and Characterization of Sucrose Synthase from the Cotyledons of
      Vicia faba L.
AB  - Partial purification (approximately 270-fold) of sucrose synthase (EC 2.4.1.13)
      from developing cotyledons of Vicia faba L. cv Maris Bead was achieved by
      ammonium sulfate fractionation and hydrophobic, affinity, anion-exchange, and gel
      filtration chromatography. Further purification to homogeneity resulted from gel
      elution of single bands from native and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The enzyme was identified as a homotetramer with a total
      molecular mass of 360 kD and subunits of 92 to 93 kD. Antibodies were raised to
      both native and denatured protein. The identity of the polypeptide was confirmed
      in western blots using antibodies raised against soybean nodule sucrose synthase.
      The enzyme has a pH optimum of 6.4 (cleavage direction) and an isoelectric point
      of 5.5. The affinity of the enzyme for sucrose (K(m)) was estimated at 169 mm,
      and for UDP at 0.2 mm. With uridine diphosphate as the nucleoside diphosphate,
      the V(max) is 4-fold higher than with adenosine diphosphate. Fructose acts as a
      competitive inhibitor with an inhibitor constant (K(i)) of 2.48 mm.

PMID- 16653009
TI  - Auxins induce tryptophan decarboxylase activity in radicles of catharanthus
      seedlings.
AB  - Germinating seedlings of Catharanthus roseus produce monoterpenoid indole
      alkaloids as a result of a transient increase of tryptophan decarboxylase (TDC)
      activity. The influence of auxins on this transient rise of TDC activity was
      studied. External application of indolebutyric acid or 2,4-dichlorophenoxyacetic
      acid at a concentration of 20 to 40 mum enhanced and prolonged the rise in TDC
      activity in developing seedlings. Auxin treatment also influenced the morphology
      of the seedlings; it induced a shortening and thickening of the hypocotyl and the
      radicle and promoted the initiation of lateral roots in the radicle. During
      development, the radicles of auxin-treated seedlings displayed a gradual increase
      in TDC activity that was absent in the radicles of untreated controls.
      Examination of immunoblots revealed anti-TDC reactive proteins in extracts from
      radicles of auxin-treated seedlings, but none in extracts from radicles of
      control seedlings. In contrast, TDC activity and immunoreactive protein levels in
      the aerial parts of controls and auxin-treated seedlings were comparable. Our
      results indicate that externally applied auxins induce both abnormal development
      and TDC activity in the radicles of Catharanthus seedlings. Although auxins
      slightly delayed the light-mediated induction of the cotyledon-specific last step
      in vindoline biosynthesis (i.e. acetylcoenzyme A: deacetylvindolin-O
      acetyltransferase activity), seedlings still synthesized vindoline, one of the
      major alkaloid end products.

PMID- 16653010
TI  - Genotypic variability in vulnerability of leaf xylem to cavitation in water
      stressed and well-irrigated sugarcane.
AB  - Genotypic variability in vulnerability of leaf xylem to water-stress-induced
      cavitation was determined in four sugarcane (Saccharum sp.) clones using detached
      leaf segments in a hydraulic conductivity apparatus. Vulnerability curves were
      constructed by plotting the percentage of maximum conductivity versus leaf water
      potential (psi(I)) and fitting curves using a Weibull function. The psi(I) at
      which each clone lost 10, 50, and 80% of maximum conductivity was determined.
      Maximum conductivity per unit of leaf width was positively associated with
      metaxylem vessel diameter. The commercial clone H65-7052 exhibited the highest
      and the nondomesticated S. spontaneum exhibited the lowest conductivity. All four
      clones lost substantial conductivity at values of psi(I) less negative than -1.4
      MPa, but H65-7052 was able to maintain 50% conductivity to lower psi(I) than the
      other clones. S. spontaneum sustained the most negative psi(I) (-1.99 MPa) before
      reaching the 80% conductivity loss point. Clone H69-8235 was consistently the
      most vulnerable to initial loss of conductivity. These vulnerability functions
      were used in conjunction with field measurements of psi(I) to estimate diurnal
      losses in leaf hydraulic conductivity under irrigated and droughted conditions.
      H69-8235 lost up to 50% of its conductivity during the day, even when well
      irrigated, and more than 80% when subjected to drought. The other clones
      exhibited lower conductivity losses. These losses are apparently reversed
      overnight by root pressure. Despite their close genetic relationships, these
      clones exhibited large differences in conductivity, in the vulnerability of their
      xylem to cavitation, and in gas exchange behavior. The potential for altering
      water relations by selecting for particular hydraulic characteristics is
      discussed.

PMID- 16653011
TI  - Phytochrome is involved in the light-regulation of vindoline biosynthesis in
      catharanthus.
AB  - The enzyme acetylcoenzyme A:deacetylvindoline 4-O-acetyl-transferase (DAT)
      catalyzes the final step in the biosynthesis of the monoterpenoid indole
      alkaloid, vindoline. Previous studies have shown that the appearance of DAT
      activity in etiolated seedlings of Catharanthus roseus is induced by exposure of
      seedlings to light and that enzyme activity is restricted principally to the
      cotyledons. Evidence is now presented that phytochrome is involved in the light
      mediated induction of DAT activity in Catharanthus cotyledons.

PMID- 16653012
TI  - Carbon isotope ratios in ear parts of triticale : influence of grain filling.
AB  - Four triticale (xTriticosecale Wittmack) genotypes were grown under rainfed
      conditions with limited irrigation support in Lleida in northeast Spain. For each
      variety, samples consisting of 10 tillers with half-sterilized spikes were taken
      three times from anthesis to maturity. Carbon isotope ratios (delta(13)C) were
      then determined in water extracts from ear bracts (glumes, paleas, and lemmas),
      awns and flag leaves, and in powdered kernels. For the half-sterilized spikes,
      carbon isotope analysis was carried out separately in bracts and awns from
      fertile and nonfertile spikelets. The delta(13)C in the water-soluble fraction of
      awns, glumes, and glumells from fruitless spikelets was significantly higher than
      that from fertile spikelets sampled at mid-grain filling. Differences in
      delta(13)C among sterile and fertile spikelets were not significant in samples
      taken a few days after anthesis or at maturity. These results are in accordance
      with some degree of refixation by awns and ear bracts of the CO(2) respired by
      grains during grain filling. There was progressively higher delta(13)C from flag
      leaf blades to awns, glumes, and glumells. This variation in delta(13)C along
      plant parts may be caused by differences in the ratio of assimilation rate to
      CO(2)-diffusive conductance. Values of delta(13)C of mature kernels were between
      the values at anthesis and mid-grain filling for the water-soluble fraction of
      flag leaves and inner bracts and were fairly similar to those of glumes and awns.

PMID- 16653013
TI  - Pressure clamp method to measure transpiration in growing single plant cells :
      demonstration with sporangiophores of phycomyces.
AB  - A pressure probe method (pressure clamp) was developed to measure transpiration
      rates of both growing and nongrowing single plant cells, and represents an
      improvement over the previous pressure probe method (pressure relaxation), which
      is restricted to nongrowing plant cells (J.K.E. Ortega, R.G. Keanini, K.J. Manica
      [1988] Plant Physiol 87: 11-14). The pressure clamp method was used to measure
      transpiration rates of Phycomyces sporangiophores in two developmental stages:
      stage III (nongrowing) and stage IV (growing).

PMID- 16653014
TI  - Artifactual Elevation of the Apparent Levels of Phosphatidic Acid and
      Phosphatidylinositol 4,5-Bisphosphate during Short-Term Labeling of Plant Tissue
      with Radioactive Precursor.
AB  - Some pulvini of Samanea saman Mehr. labeled with radioactive phosphate show
      apparent remarkable elevations of the levels of phosphatidic acid and
      phosphatidylinositol 4,5-bisphosphate. The elevated levels, however, appear to be
      illusory and to result from rapid initial incorporation of label into these
      phospholipids relative to others. These results demonstrate the need for caution
      in interpreting apparent changes in the levels of phosphatidic acid or inositol
      phospholipids in cultures or plants labeled with radioactive precursors.

PMID- 16653015
TI  - Kinetics of Maize Leaf Elongation : III. Silver Thiosulfate Increases the Yield
      Threshold of Salt-Stressed Plants, but Ethylene Is Not Involved.
AB  - The involvement of ethylene in the short-term responses of maize (Zea mays L.)
      leaf elongation to salinity was investigated. Leaf elongation rates (LER) were
      monitored with linear variable differential transformers. Salinity (80 mm NaCl)
      rapidly inhibited LER. Pretreatment with 4 mm silver thiosulfate (STS), an
      inhibitor of ethylene action, decreased LER of salt-stressed plants, but not that
      of controls. Investigation of the growth parameters affected by the interaction
      of STS and salinity indicated that the yield threshold was increased and the cell
      wall extensibility was decreased. All other growth parameters controlling cell
      elongation were unaffected. Further investigation indicated that ethylene
      production may not be involved in this reponse because treatments with 10 mum
      aminoethoxyvinylglycine, an ethylene biosynthesis inhibitor, did not affect the
      growth of salt-stressed plants, and no increase in ethylene production was
      detected in salt-stressed plants compared with controls. No changes in
      sensitivity to ethylene were evident because LER of both control and salt
      stressed plants were inhibited to the same extent with exposure to 1.2 ppm
      ethylene. The above evidence indicated that ethylene was not involved in the
      short-term LER responses of salt-stressed maize.

PMID- 16653016
TI  - Isolation and characterization of a cDNA clone encoding the major hsp70 of the
      pea chloroplastic stroma.
AB  - The 70-kD heat shock proteins (hsp70s) are a group of ubiquitous, highly
      conserved molecular chaperones that have been implicated in a variety of
      processes, ranging from DNA replication to protein folding and transport. To
      learn more about the evolution and possible functions of higher plant
      chloroplastic hsp70s, we isolated a cDNA clone encoding the major stromal hsp70
      of pea chloroplasts, which we term CSS1 (Chloroplastic Stress Seventy). This cDNA
      clone encodes a 75,490-D protein that is very closely related to an hsp70 from
      the cyanobacterium, Synechocystis. CSS1 is nuclear encoded and synthesized as a
      higher molecular mass precursor with a chloroplastic transit peptide
      approximately 65 amino acids long. CSS1 mRNA was detected in RNA samples from
      leaves and roots of pea (Pisum sativum) plants grown at 18 degrees C but
      increased 9- and 6-fold, respectively, after brief exposure of the plants to
      elevated temperature. We discuss the possible role(s) of CSS1 in chloroplastic
      protein transport and other processes.

PMID- 16653017
TI  - In Vitro Antifungal Activity of a Radish (Raphanus sativus L.) Seed Protein
      Homologous to Nonspecific Lipid Transfer Proteins.
AB  - A basic 9-kD protein was purified from seeds of radish (Raphanus sativus L.). The
      43 amino-terminal amino acids show extensive sequence identity with nonspecific
      lipid transfer proteins from other plant species. The radish seed nonspecific
      lipid transfer protein-like protein inhibits the growth of several fungi in
      vitro.

PMID- 16653018
TI  - Isolation and identification of lepidimoide, a new allelopathic substance from
      mucilage of germinated cress seeds.
AB  - A new allelopathic substance that promoted the shoot growth of different plant
      species but inhibited the root growth was isolated as an amorphous powder from
      mucilage of germinated cress (Lepidium sativum L.) seeds. This substance was
      identified as sodium 2-O-rhamnopyranosyl-4-deoxy-threo-hex-4-enopyranosiduronate
      (designated lepidimoide) from the mass and the nuclear magnetic resonance and
      infrared spectra coupled with some chemical evidence. Lepidimoide promoted the
      hypocotyl growth of etiolated Amaranthus caudatus L. at concentrations higher
      than 3 mum and inhibited the root growth at concentrations higher than 100 mum.
      The growth-promoting activity in hypocotyls was 20 or 30 times as much as that of
      gibberellic acid.

PMID- 16653019
TI  - Conversion of proplastids to amyloplasts in tobacco cultured cells is accompanied
      by changes in the transcriptional activities of plastid genes.
AB  - When tobacco (Nicotiana tabacum L.) cultured cells (line BY-2) at the stationary
      phase were transferred to culture medium that contained cytokinin (benzyladenine)
      instead of auxin (2,4-dichlorophenoxyacetic acid), proplastids in the BY-2 cells
      were converted to amyloplasts within 48 h. The data obtained from in vitro
      transcription assays using isolated plastid-nucleoids (nuclei) strongly suggested
      that amyloplast formation in BY-2 cells was accompanied by changes in the
      transcriptional activities of plastid genes.

PMID- 16653020
TI  - Nucleotide sequence of an abscisic Acid-responsive, embryo-specific maize gene.

PMID- 16653021
TI  - Complementary DNA Sequence of an Adenylate Translocator from Arabidopsis
      thaliana.

PMID- 16653022
TI  - cDNA Sequence of PsPK5, a Protein Kinase Homolog from Pisum sativum L.

PMID- 16653023
TI  - Cloning and Sequencing of a Second cDNA Encoding 3-Deoxy-d-arabino-Heptulosonate
      7-Phosphate Synthase from Solanum tuberosum L.

PMID- 16653024
TI  - Nucleotide sequence of a complementary DNA encoding tobacco chloroplastic
      carbonic anhydrase.

PMID- 16653025
TI  - Sequences of the Chlamydomonas reinhardtii Chloroplast Genes Encoding tRNA and
      Ribosomal Protein L20.

PMID- 16653026
TI  - Modification of fruit ripening by suppressing gene expression.

PMID- 16653027
TI  - The enzymic reduction of glyoxylate and hydroxypyruvate in leaves of higher
      plants.
AB  - Glyoxylate and hydroxypyruvate are metabolites involved in the pathway of carbon
      in photorespiration. The chief glyoxylate-reducing enzyme in leaves is now known
      to be a cytosolic glyoxylate reductase that uses NADPH as the preferred cofactor
      but can also use NADH. Glyoxylate reductase has been isolated from spinach
      leaves, purified to homogeneity, and characterized kinetically and structurally.
      Chloroplasts contain lower levels of glyoxylate reductase activity supported by
      both NADPH and NADH, but it is not yet known whether a single chloroplastic
      enzyme catalyzes glyoxylate reduction with both cofactors. The major
      hydroxypyruvate reductase activity of leaves has long been known to be a highly
      active enzyme located in peroxisomes; it uses NADH as the preferred cofactor. To
      a lesser extent, NADPH can also be used by the peroxisomal enzyme. A second
      hydroxypyruvate reductase enzyme is located in the cytosol; it preferentially
      uses NADPH but can also use NADH as cofactor. In a barley mutant deficient in
      peroxisomal hydroxypyruvate reductase, the NADPH-preferring cytosolic form of the
      enzyme permits sufficient rates of hydroxypyruvate reduction to support continued
      substrate flow through the terminal stages of the photosynthetic carbon oxidation
      (glycolate/glycerate) pathway. The properties and metabolic significance of the
      cytosolic and organelle-localized glyoxylate and hydroxypyruvate reductase
      enzymes are discussed.

PMID- 16653028
TI  - Partitioning of malate dehydrogenase isoenzymes into glyoxysomes, mitochondria,
      and chloroplasts.
AB  - Malate dehydrogenase isoenzymes catalyzing the oxidation of malate to
      oxaloacetate are highly active enzymes in mitochondria, in peroxisomes, in
      chloroplasts, and in the cytosol. Determination of the primary structure of the
      isoenzymes has disclosed that they are encoded in different nuclear genes. All
      three organelle-targeted malate dehydrogenases are synthesized with an amino
      terminal extension that is cleaved off in connection with the import of the
      enzyme precursor into the organelle. The sequence of the 27 amino acids of the
      mitochondrial transit peptide is unrelated to the 37-residue glyoxysomal transit
      peptide, which in turn is entirely different in sequence from the 57-residue
      chloroplastic transit peptide. With the exception of malate dehydrogenase and 3
      ketoacyl thiolase, peroxisomal enzymes are synthesized without transit peptides
      and are frequently translocated into the organelle with a peroxisomal targeting
      signal consisting of a conserved tripeptide at the carboxy terminus of the
      protein. Based on the observation that this tripeptide (Ala-His-Leu) occurs in
      the transit peptides of glyoxysomal malate dehydrogenase and peroxisomal 3
      ketoacyl thiolase, the possible significance of amino terminal transit peptides
      for peroxisome import is discussed.

PMID- 16653029
TI  - Is there an alternative pathway for starch synthesis?
AB  - In leaf tissue, carbon enters starch via the gluconeogenesis pathway where d
      glycerate 3-phosphate formed from CO(2) fixation is converted into hexose
      monophosphates within the chloroplast stroma. In starch-containing sink organs,
      evidence has been obtained indicating that the flow of carbon into starch follows
      a different pathway whereby hexose monophosphates formed from sucrose are
      transported into the amyloplast, a plastid specialized in starch accumulation. In
      both chloroplasts and amyloplasts, the formation of ADPglucose, the substrate for
      starch synthase, is controlled by the activity of ADPglucose pyrophosphorylase, a
      key regulatory enzyme of starch synthesis localized in the plastid. Recently, an
      alternative pathway of starch synthesis has been proposed in which ADPglucose is
      synthesized from sucrose and transported directly into the plastid compartment,
      where it is used for starch synthesis. On the basis of the biochemical phenotypes
      exhibited by various plant mutants with defined genetic lesions, it is concluded
      that ADPglucose pyrophosphorylase is essential for starch synthesis, whereas the
      alternative pathway has only a minor role in this process.

PMID- 16653030
TI  - Iron-induced changes in light harvesting and photochemical energy conversion
      processes in eukaryotic marine algae.
AB  - The role of iron in regulating light harvesting and photochemical energy
      conversion processes was examined in the marine unicellular chlorophyte
      Dunaliella tertiolecta and the marine diatom Phaeodactylum tricornutum. In both
      species, iron limitation led to a reduction in cellular chlorophyll
      concentrations, but an increase in the in vivo, chlorophyll-specific, optical
      absorption cross-sections. Moreover, the absorption cross-section of photosystem
      II, a measure of the photon target area of the traps, was higher in iron-limited
      cells and decreased rapidly following iron addition. Iron-limited cells exhibited
      reduced variable/maximum fluorescence ratios and a reduced fluorescence per unit
      absorption at all wave-lengths between 400 and 575 nm. Following iron addition,
      variable/maximum fluorescence ratios increased rapidly, reaching 90% of the
      maximum within 18 to 25 h. Thus, although more light was absorbed per unit of
      chlorophyll, iron limitation reduced the transfer efficiency of excitation energy
      in photosystem II. The half-time for the oxidation of primary electron acceptor
      of photosystem II, calculated from the kinetics of decay of variable maximum
      fluorescence, increased 2-fold under iron limitation. Quantitative analysis of
      western blots revealed that cytochrome f and subunit IV (the plastoquinone
      docking protein) of the cytochrome b(6)/f complex were also significantly reduced
      by lack of iron; recovery from iron limitation was completely inhibited by either
      cycloheximide or chloramphenicol. The recovery of maximum photosynthetic energy
      conversion efficiency occurs in three stages: (a) a rapid (3-5 h) increase in
      electron transfer rates on the acceptor side of photosystem II correlated with de
      novo synthesis of the cytochrome b(6)/f complex; (b) an increase (10-15 h) in the
      quantum efficiency correlated with an increase in D1 accumulation; and (c) a slow
      (>18 h) increase in chlorophyll levels accompanied by an increase in the
      efficiency of energy transfer from the light-harvesting chlorophyll proteins to
      the reaction centers.

PMID- 16653031
TI  - Hormonal and Environmental Regulation of the Carrot lea-Class Gene Dc3.
AB  - Dc3 is a carrot lea-class gene belonging to a small gene family that encodes Dc3
      and Dc3-like RNA sequences. We have examined the responsiveness to water deficit
      and abscisic acid (ABA) of the promoter/enhancer complex of Dc3 fused to a beta
      glucuronidase (GUS) reporter gene in vegetative cells of transgenic tobacco. In
      56-d tobacco, GUS expression in leaves increased about 200-fold during a 3-d
      drying cycle, during which there were small decreases (3 atmospheres or less) in
      leaf water potential and a 16-fold increase in free ABA. These effects were
      reversed by rewatering. Changes in GUS activity were closely paralleled by
      changes in GUS transcript levels during the desiccation/watering cycle,
      indicating transcriptional regulation of GUS gene expression. The Dc3 promoter
      responds to exogenous ABA; the effect is time and concentration dependent, with
      greater than 10-fold induction in 8 h with 10 mum ABA. Histochemical
      visualization of GUS activity in seedlings induced by water deficit or exogenous
      ABA revealed Dc3-driven GUS expression in all organs of transgenic tobacco
      seedlings. We suggest that the Dc3/GUS reporter system is a sensitive analytical
      tool to study various environmental effects on plant growth and development.

PMID- 16653032
TI  - A Phosphoribosylanthranilate Transferase Gene Is Defective in Blue Fluorescent
      Arabidopsis thaliana Tryptophan Mutants.
AB  - An Arabidopsis thaliana gene encoding phosphoribosylanthranilate transferase is
      shown to be the gene that is defective in blue fluorescent trp1 mutant plants.
      This gene, named PAT1, was isolated using an A. thaliana cDNA clone that
      suppressed an Escherichia coli trpD(-) mutation. The PAT1 coding region is
      homologous to those for the phosphoribosylanthranilate transferases from many
      microorganisms. Unlike other genes involved in aromatic amino acid biosynthesis
      in A. thaliana, PAT1 appears to be a single-copy gene. PAT1 was demonstrated to
      be the gene that is defective in blue fluorescent trp1 mutants by two methods:
      genetic complementation in transgenic plants and genetic mapping studies. This is
      the first report of cloning a plant phosphoribosylanthranilate transferase gene.
      The PAT1 gene should prove useful as a selectable marker for transformation or a
      visible reporter of gene expression when used in conjunction with trp1 plants.

PMID- 16653033
TI  - Antifreeze protein produced endogenously in winter rye leaves.
AB  - After cold acclimation, winter rye (Secale cereale L.) is able to withstand the
      formation of extracellular ice at freezing temperatures. We now show, for the
      first time, that cold-acclimated winter rye plants contain endogenously produced
      antifreeze protein. The protein was extracted from the apoplast of winter rye
      leaves, where ice forms during freezing. After partial purification, the protein
      was identified as antifreeze protein because it modified the normal growth
      pattern of ice crystals and depressed the freezing temperature of water
      noncolligatively.

PMID- 16653034
TI  - Labeling of Carbon Pools in Bradyrhizobium japonicum and Rhizobium leguminosarum
      bv viciae Bacteroids following Incubation of Intact Nodules with CO(2).
AB  - The aim of the work reported here was to ascertain that the patterns of labeling
      seen in isolated bacteroids also occurred in bacteroids in intact nodules and to
      observe early metabolic events following exposure of intact nodules to (14)CO(2).
      Intact nodules of soybean (Glycine max L. Merr. cv Ripley) inoculated with
      Bradyrhizobium japonicum USDA 110 and pea (Pisum sativum L. cv Progress 9)
      inoculated with Rhizobium leguminosarum bv viciae isolate 128C53 were detached
      and immediately fed (14)CO(2) for 1 to 6 min. Bacteroids were purified from these
      nodules in 5 to 7 min after the feeding period. In the cytosol from both soybean
      and pea nodules, malate had the highest radioactivity, followed by citrate and
      aspartate. In peas, asparagine labeling equaled that of aspartate. In B.
      japonicum bacteroids, malate was the most rapidly labeled compound, and the rate
      of glutamate labeling was 67% of the rate of malate labeling. Aspartate and
      alanine were the next most rapidly labeled compounds. R. leguminosarum bacteroids
      had very low amounts of (14)C and, after a 1-min feeding, malate contained 90% of
      the radioactivity in the organic acid fraction. Only a trace of activity was
      found in aspartate, whereas the rate of glutamate and alanine labeling approached
      that of malate after 6 min of feeding. Under the conditions studied, malate was
      the major form of labeled carbon supplied to both types of bacteroids. These
      results with intact nodules confirm our earlier results with isolated bacteroids,
      which showed that a significant proportion of provided labeled substrate, such as
      malate, is diverted to glutamate. This supports the conclusion that microaerobic
      conditions in nodules influence carbon metabolism in bacteroids.

PMID- 16653035
TI  - Xylem embolism in response to freeze-thaw cycles and water stress in ring-porous,
      diffuse-porous, and conifer species.
AB  - Vulnerability to xylem embolism by freeze-thaw cycles and water stress was
      quantified in ring-porous (Quercus gambelii Nutt.), diffuse-porous (Populus
      tremuloides Michx., Betula occidentalis Hook.), and conifer species (Abies
      lasiocarpa Nutt., Juniperus scopulorum Sarg.). Embolism was measured by its
      reduction of xylem hydraulic conductivity; it was induced by xylem tension (water
      stress response) and by a tension plus a freeze-thaw cycle (freeze response).
      Conifers showed little (Juniperus) or no (Abies) freeze response even to repeated
      cycles. In contrast, Quercus embolized more than 90% by freezing at tensions
      below 0.2 MPa, whereas similar embolism without freezing required tensions above
      4.5 MPa. Diffuse-porous trees (Betula, Populus) showed an intermediate freeze
      response. The magnitude of the freeze response was correlated with conduit volume
      but occurred at higher tensions than predicted from theory. Large early-wood
      vessels (2.8 x 10(-9) m(3)) in oak were most vulnerable to embolism by freezing,
      small vessels in Populus and Betula were intermediate (approximately 7 x 10(-11)
      m(3)), and tracheids in conifers (about 3 x 10(-13) m(3)) were most resistant.
      The same trend was found within a stem: embolism by freeze-thawing occurred
      preferentially in wider conduits. The water-stress response was not correlated
      with conduit volume; previous work indicates it is a function of interconduit pit
      membrane structure. Native embolism levels during winter corroborated laboratory
      results on freezing: Quercus embolized 95% with the first fall freeze, Populus
      and Betula showed gradual increases to more than 90% embolism by winter's end,
      and Abies remained below 30%.

PMID- 16653036
TI  - Electric current precedes emergence of a lateral root in higher plants.
AB  - Stable electrochemical patterns appear spontaneously around roots of higher
      plants and are closely related to growth. An electric potential pattern
      accompanied by lateral root emergence was measured along the surface of the
      primary root of adzuki bean (Phaseolus angularis) over 21 h using a
      microelectrode manipulated by a newly developed apparatus. The electric potential
      became lower at the point where a lateral root emerged. This change preceded the
      emergence of the lateral root by about 10 h. A theory is presented for
      calculating two-dimensional patterns of electric potential and electric current
      density around the primary root (and a lateral root) using only data on the one
      dimensional electric potential measured near the surface of the primary root. The
      development of the lateral root inside the primary root is associated with the
      influx of electric current of about 0.7 muA.cm(-2) at the surface.

PMID- 16653037
TI  - Lack of Types 1 and 2A Protein Serine(P)/Threonine(P) Phosphatase Activities in
      Chloroplasts.
AB  - Protein phosphatase activity in crude leaf extracts and in purified intact
      chloroplasts of wheat (Triticum aestivum) and pea (Pisum sativum) was analyzed
      using exogenously supplied phosphoproteins or endogenous thylakoid proteins. Leaf
      extracts contain readily detectable amounts of protein phosphatase activity
      measured with either phosphohistone or phosphorylase a, substrates of mammalian
      protein phosphatases. No significant chloroplast protein phosphatase activity was
      detected using these exogenous phosphoproteins. The dephosphorylation of
      endogenous thylakoid light-harvesting chlorophyll a/b binding proteins in situ
      was inhibited by fluoride, but not by microcystin-LR or okadaic acid, diagnostic
      inhibitors of mammalian types 1 and 2A protein phosphatases. Additionally, no
      evidence for a pea chloroplast alkaline phosphatase activity was found using beta
      glycerolphosphate or 4-methylum-belliferyl phosphate as substrates. From these
      results, we conclude that phosphohistone and phosphorylase a are not useful
      substrates for chloroplast thylakoid protein phosphatase activity and that the
      chloroplast enzymes may not fit into one of the canonical classifications
      currently used for protein phosphatases.

PMID- 16653038
TI  - Inhibition of Gibberellin Production in the Fungi Gibberella fujikuroi and
      Sphaceloma manihoticola by Plant Growth Retardants.
AB  - The effect of different types of plant growth retardants on fungal gibberellin
      (GA) formation has been studied in cultures of Gibberella fujikuroi and
      Sphaceloma manihoticola. Quaternary ammonium compounds (chlormequat chloride,
      mepiquat chloride, Amo-1618), triazoles (uniconazole and several experimental
      compounds), and the norbornanodiazetine tetcyclacis inhibited GA biosynthesis in
      both fungal species. Concentrations between 2 x 10(-4) and 10(-9)m were required
      for a 50% inhibition of the production of gibberellin A(3) in Gibberella
      fujikuroi and of giberellin A(4) in Sphaceloma manihoticola. The formation of
      other prominent GAs was affected at a similar degree of intensity. Tetcyclacis
      was the most active compound in both fungi. Compared to the growth retardants
      mentioned above, the biological activity of chlorphonium chloride was low. The
      acylcyclohexanediones prohexadione and LAB 198 999 had virtually no activity.
      Most likely, this lack of activity is due to a rapid metabolism of the compounds
      in the cultures. For the triazole-type compounds and tetcyclacis, a relatively
      distinct correlation exists in their ability to inhibit GA formation in fungal
      cultures, to block ent-kaurene oxygenase in a cell-free system, and to reduce
      shoot growth of rice seedlings. Due to differences in their metabolic fate and
      species specificities, such conclusions cannot be made for the other compounds.

PMID- 16653039
TI  - On the Mechanism of Resistance to Paraquat in Hordeum glaucum and H. leporinum:
      Delayed Inhibition of Photosynthetic O(2) Evolution after Paraquat Application.
AB  - The mechanism of resistance to paraquat was investigated in biotypes of Hordeum
      glaucum Steud. and H. leporinum Link. with high levels of resistance. Inhibition
      of photosynthetic O(2) evolution after herbicide application was used to monitor
      the presence of paraquat at the active site. Inhibition of photosynthetic O(2)
      evolution after paraquat application was delayed in both resistant biotypes
      compared with the susceptible biotypes; however, this differential was more
      pronounced in the case of H. glaucum than in H. leporinum. Similar results could
      be obtained with the related herbicide diquat. Examination of the concentration
      dependence of paraquat-induced inhibition of O(2) evolution showed that the
      resistant H. glaucum biotype was less affected by herbicide compared with the
      susceptible biotype 3 h after treatment at most rates. The resistant H. leporinum
      biotype, in contrast, was as inhibited as the susceptible biotype except at the
      higher rates. In all cases photosynthetic O(2) evolution was dramatically
      inhibited 24 h after treatment. Measurement of the amount of paraquat transported
      to the young tissue of these plants 24 h after treatment showed 57% and 53%
      reductions in the amount of herbicide transported in the case of the resistant H.
      glaucum and H. leporinum biotypes, respectively, compared with the susceptible
      biotypes. This was associated with 62% and 66% decreases in photosynthetic O(2)
      evolution of young leaves in the susceptible H. glaucum and H. leporinum
      biotypes, respectively, a 39% decrease in activity for the resistant H. leporinum
      biotype, but no change in the resistant H. glaucum biotype. Photosynthetic O(2)
      evolution of leaf slices from resistant H. glaucum was not as inhibited by
      paraquat compared with the susceptible biotype; however, those of resistant and
      susceptible biotypes of H. leporinum were equally inhibited by paraquat. Paraquat
      resistance in these two biotypes appears to be a consequence of reduced movement
      of the herbicide in the resistant plants; however, the mechanism involved is not
      the same in H. glaucum as in H. leporinum.

PMID- 16653040
TI  - Regulation of Calcium Influx in Chara: Effects of K, pH, Metabolic Inhibition,
      and Calcium Channel Blockers.
AB  - Measurements were made of (45)Ca influx into isolated internodal cells of Chara
      corallina and also into internodal cells of intact plants. (45)Ca influx was
      closely related to growth. In rapidly expanding internodal cells, the influx was
      approximately 1.4 nmol m(-2) s(-1) compared to the influx in mature cells from
      slow-growing cultures of 0.2 nmol m(-2) s(-1). Isolated internodal cells had
      influxes in the range 0.2 to 0.7 nmol m(-2) s(-1), but this increased to
      approximately 2 nmol m(-2) s(-1) in high calcium solutions and to 4 nmol m(-2) s(
      1) in high potassium solutions. No significant effects on calcium influx were
      observed for changes in external pH or for treatments that changed internal pH,
      except that NH(4) was slightly inhibitory. Severe metabolic inhibition by
      carbonylcyanide-m-chlorophenyl-hydrazone stimulated influx, whereas
      dicyclohexylcarbodiimide had no effect and darkness inhibited influx. La(3+) also
      inhibited influx, but the organic channel blockers nifedipine and bepridil
      stimulated influx. Verapamil had no effect. The results are generally consistent
      with voltage regulation of calcium channels as in animal cells.

PMID- 16653041
TI  - Effects of nitrite, chlorate, and chlorite on nitrate uptake and nitrate
      reductase activity.
AB  - Effects of NO(2) (-), ClO(3) (-), and ClO(2) (-) on the induction of nitrate
      transport and nitrate reductase activity (NRA) as well as their effects on NO(3)
      (-) influx into roots of intact barley (Hordeum vulgare cv Klondike) seedlings
      were investigated. A 24-h pretreatment with 0.1 mol m(-3) NO(2) (-) fully induced
      NO(3) (-) transport but failed to induce NRA. Similar pretreatments with ClO(3) (
      ) and ClO(2) (-) induced neither NO(3) (-) transport nor NRA. Net ClO(3) (-)
      uptake was induced by NO(3) (-) but not by ClO(3) (-) itself, indicating that
      NO(3) (-) and ClO(3) (-) transport occur via the NO(3) (-) carrier. At the uptake
      step, NO(2) (-) and ClO(2) (-) strongly inhibited NO(3) (-) influx; the former
      exhibited classical competitive kinetics, whereas the latter exhibited complex
      mixed-type kinetics. ClO(3) (-) proved to be a weak inhibitor of NO(3) (-) influx
      (K(i) = 16 mol m(-3)) in a noncompetitive manner. The implications of these
      findings are discussed in the context of the suitability of these NO(3) (-)
      analogs as screening agents for the isolation of mutants defective in NO(3) (-)
      transport.

PMID- 16653042
TI  - Use of an Acylcyclohexanedione Growth Retardant, LAB 198 999, to Determine
      Whether Gibberellin A(20) Has Biological Activity per se in Dark-Grown Dwarf (le)
      Seedlings of Pisum sativum.
AB  - Dwarf (le(5839)) seedlings of Pisum sativum respond to gibberellin A(20) (GA(20))
      in the dark, although the same dosage of GA(20) applied to light-grown le(5839)
      seedlings elicits no growth response. The acylcyclohexanedione growth retardant,
      LAB 198 999, which is known to inhibit gibberellin oxidation and in particular
      3beta-hydroxylation such as the conversion of GA(20) to GA(1), also inhibits the
      growth response of dark-grown dwarf (le(5839)) seedlings to GA(20). Thus, the
      biological activity of GA(20) in the dark appears to be a consequence of its
      conversion to GA(1), even though it is known from studies with light-grown
      seedlings that the le mutation reduces the conversion of GA(20) to GA(1).

PMID- 16653043
TI  - Blue light activates a specific protein kinase in higher plants.
AB  - Blue light mediates the phosphorylation of a membrane protein in seedlings from
      several plant species. When crude microsomal membrane proteins from dark-grown
      pea (Pisum sativum L.), sunflower (Helianthus annuus L.), zucchini (Cucurbita
      pepo L.), Arabidopsis (Arabidopsis thaliana L.), or tomato (Lycopersicon
      esculentum L.) stem segments, or from maize (Zea mays L.), barley (Hordeum
      vulgare L.), oat (Avena sativa L.), wheat (Triticum aestivum L.), or sorghum
      (Sorghum bicolor L.) coleoptiles are illuminated and incubated in vitro with
      [gamma-(32)P]ATP, a protein of apparent molecular mass from 114 to 130 kD is
      rapidly phosphorylated. Hence, this system is probably ubiquitous in higher
      plants. Solubilized maize membranes exposed to blue light and added to
      unirradiated solubilized maize membranes show a higher level of phosphorylation
      of the light-affected protein than irradiated membrane proteins alone, suggesting
      that an unirradiated substrate is phosphorylated by a light-activated kinase.
      This finding is further demonstrated with membrane proteins from two different
      species, where the phosphorylated proteins are of different sizes and, hence,
      unambiguously distinguishable on gel electrophoresis. When solubilized membrane
      proteins from one species are irradiated and added to unirradiated membrane
      proteins from another species, the unirradiated protein becomes phosphorylated.
      These experiments indicate that the irradiated fraction can store the light
      signal for subsequent phosphorylation in the dark. They also support the
      hypothesis that light activates a specific kinase and that the systems share a
      close functional homology among different higher plants.

PMID- 16653044
TI  - A Sulfonylurea Herbicide Resistance Gene from Arabidopsis thaliana as a New
      Selectable Marker for Production of Fertile Transgenic Rice Plants.
AB  - A mutant acetolactate synthase (ALS) gene, csr1-1, isolated from sulfonylurea
      herbicide-resistant Arabidopsis thaliana, was placed under control of a
      cauliflower mosaic virus 35S promoter (35S). Rice protoplasts were transformed
      with the 35S/ALS chimeric gene and regenerated into fertile transgenic rice
      (Oryza sativa) plants. The 35S/ALS gene was expressed effectively as demonstrated
      by northern blot hybridization analysis, and conferred to transformed calli at
      least 200-fold greater chlorsulfuron resistance than nontransformed control
      calli. Effective selection of 35S/ALS-transformed protoplasts was achieved at
      extremely low chlorsulfuron concentrations of 10 nm. The results demonstrated
      that the 35S/ALS gene is an alternative selectable marker for rice protoplast
      transformation and fertile transgenic rice production. The results also suggest
      that the mutant form of Arabidopsis ALS enzyme operates normally in rice cells.
      Thus, the mechanism of protein transport to chloroplast and ALS inhibition by
      chlorsulfuron is apparently conserved among plant species as diverse as
      Arabidopsis (dicotyledon) and rice (monocotyledon).

PMID- 16653045
TI  - Hydraulic Conductivity Recovery versus Water Pressure in Xylem of Acer saccharum.
AB  - Experiments were conducted to determine the influence of stem diameter, xylem
      pressure potential, and temperature on the rate of recovery of hydraulic
      conductivity in embolized stems of Acer saccharum Marsh. Recovery of conductivity
      was accompanied by an increase in stem water content as water replaced air
      bubbles and bubbles dissolved from vessels into the surrounding water. The time
      required for stems to go from less than 3 to 100% hydraulic conductivity
      increased approximately with the square of the stem diameter and increased with
      decreasing xylem pressure potential. Recovery was halted when xylem pressure
      potential decreased below -6 kPa. Increasing xylem pressure from 13 to 150 kPa
      reduced the time for recovery by a factor of 4. Temperature had little influence
      on the rate of recovery of hydraulic conductivity. All of these results are in
      accord with a theory of bubble dissolution in which it is assumed that: (a) the
      rate of bubble dissolution is rate limited by diffusion of air from the bubbles
      to the outer surface of the stems, (b) the equilibrium concentration of gases in
      liquid in stems is determined by Henry's law at all air-water interfaces, (c) the
      equilibrium solubility concentration is determined only by the partial pressure
      of the gas in the gas phase and not directly by the liquid-phase pressure, and
      (d) the gas pressure of an entrapped air bubble in the lumen of a cell can never
      be less than atmospheric pressure at equilibrium.

PMID- 16653046
TI  - Purification and Characterization of Polyphenol Oxidase from Glandular Trichomes
      of Solanum berthaultii.
AB  - Type A glandular trichomes of the wild potato (Solanum berthaultii Hawkes) entrap
      insects by rapidly polymerizing the trichome contents after breakage by insect
      contact. Polymerization of trichome exudate appears to be driven by a soluble
      polyphenol oxidase (PPO). PPO constitutes up to 70% of the protein in
      individually collected trichomes and reaches a concentration approaching 200 mum
      in these organs. Trichome PPO has been purified and shown to be a monomeric
      copper metalloprotein with an isoelectric point of 5.5, possessing only o
      diphenol oxygen oxido-reductase activity, and is larger than most other reported
      PPOs, with relative molecular weight of 59,000. Chlorogenic and caffeic acid were
      the most readily oxidized of 14 phenolic substrates tested. Polyclonal antibodies
      raised against the relative molecular weight 59,000 S. berthaultii trichome PPO
      were used to show that S. tuberosum L. trichomes express low levels of a cross
      reactive protein that lacks detectable PPO activity.

PMID- 16653047
TI  - Photosynthetic Light Utilization Efficiency, Photosystem II Heterogeneity, and
      Fluorescence Quenching in Chlamydomonas reinhardtii during the Induction of the
      CO(2)-Concentrating Mechanism.
AB  - The photosynthetic light-response curve, the relative amounts of the different
      photosystem II (PSII) units, and fluorescence quenching were altered in an
      adaptive manner when CO(2)-enriched wild-type Chlamydomonas reinhardtii cells
      were transferred to low levels of CO(2). This treatment is known to result in the
      induction of an energy-dependent CO(2)-concentrating mechanism (CCM) that
      increases the internal inorganic carbon concentration and thus the photosynthetic
      CO(2) utilization efficiency. After 3 to 6 h of low inorganic carbon treatment,
      several changes in the photosynthetic energy-transducing reactions appeared and
      proceeded for about 12 h. After this time, the fluorescence parameter
      variable/maximal fluorescence yield and the amounts of both PSIIalpha and
      PSIIbeta (secondary quinone electron acceptor of PSII-reducing) centers had
      decreased, whereas the amount of PSIIbeta (secondary quinone electron acceptor of
      PSII-nonreducing) centers had increased. The yield of noncyclic electron
      transport also decreased during the induction of the CCM, whereas both
      photochemical and nonphotochemical quenching of PSII fluorescence increased.
      Concurrent with these changes, the photosynthetic light-utilization efficiency
      also decreased significantly, largely attributed to a decline in the curvature
      parameter theta, the convexity of the photosynthetic light-response curve. Thus,
      it is concluded that the increased CO(2) utilization efficiency in algal cells
      possessing the CCM is maintained at the cost of a reduced light utilization
      efficiency, most probably due to the reduced energy flow through PSII.

PMID- 16653048
TI  - Cytosolic alkalinization mediated by abscisic Acid is necessary, but not
      sufficient, for abscisic Acid-induced gene expression in barley aleurone
      protoplasts.
AB  - We investigated whether intracellular pH (pH(i)) is a causal mediator in abscisic
      acid (ABA)-induced gene expression. We measured the change in pH(i) by a "null
      point" method during stimulation of barley (Hordeum vulgare cv Himalaya) aleurone
      protoplasts with ABA and found that ABA induces an increase in pH(i) from 7.11 to
      7.30 within 45 min after stimulation. This increase is inhibited by plasma
      membrane H(+)-ATPase inhibitors, which induce a decrease in pH(i), both in the
      presence and absence of ABA. This ABA-induced pH(i) increase precedes the
      expression of RAB-16 mRNA, as measured by northern analysis. ABA-induced pH(i)
      changes can be bypassed or clamped by addition of either the weak acids 5,5
      dimethyl-2,4-oxazolidinedione and propionic acid, which decrease the pH(i), or
      the weak bases methylamine and ammonia, which increase the pH(i). Artificial
      pH(i) increases or decreases induced by weak bases or weak acids, respectively,
      do not induce RAB-16 mRNA expression. Clamping of the pH(i) at a high value with
      methylamine or ammonia treatment affected the ABA-induced increase of RAB-16 mRNA
      only slightly. However, inhibition of the ABA-induced pH(i) increase with weak
      acid or proton pump inhibitor treatments strongly inhibited the ABA-induced RAB
      16 mRNA expression. We conclude that, although the ABA-induced the pH(i) increase
      is correlated with and even precedes the induction of RAB-16 mRNA expression and
      is an essential component of the transduction pathway leading from the hormone to
      gene expression, it is not sufficient to cause such expression.

PMID- 16653049
TI  - Comparative studies of the light modulation of nitrate reductase and sucrose
      phosphate synthase activities in spinach leaves.
AB  - We recently obtained evidence that the activity of spinach (Spinacia oleracea L.)
      leaf nitrate reductase (NR) responds rapidly and reversibly to light/dark
      transitions by a mechanism that is strongly correlated with protein
      phosphorylation. Phosphorylation of the NR protein appears to increase
      sensitivity to Mg(2+) inhibition, without affecting activity in the absence of
      Mg(2+). In the present study, we have compared the light/dark modulation of
      sucrose-phosphate synthase (SPS), also known to be regulated by protein
      phosphorylation, and NR activities (assayed with and without Mg(2+)) in spinach
      leaves. There appears to be a physiological role for both enzymes in mature
      source leaves (production of sucrose and amino acids for export), whereas NR is
      also present and activated by light in immature sink leaves. In mature leaves,
      there are significant diurnal changes in SPS and NR activities (assayed under
      selective conditions where phosphorylation status affects enzyme activity) during
      a normal day/night cycle. With both enzymes, activities are highest in the
      morning and decline as the photoperiod progresses. For SPS, diurnal changes are
      largely the result of phosphorylation/dephosphorylation, whereas with NR, the
      covalent modification is super-imposed on changes in the level of NR protein.
      Accumulation of end products of photosynthesis in excised illuminated leaves
      increased maximum NR activity, reduced its sensitivity of Mg(2+) inhibition, and
      prevented the decline in activity with time in the light seen with attached
      leaves. In contrast, SPS was rapidly inactivated in excised leaves. Overall, NR
      and SPS share many common features of control but are not identical in terms of
      regulation in situ.

PMID- 16653050
TI  - Phosphorus Distribution in Red Pine Roots and the Ectomycorrhizal Fungus Hebeloma
      arenosa.
AB  - Red pines (Pinus resinosa Ait.) were grown in a pasteurized sandy loam either
      unamended with phosphate or fertilized with one of two levels of phosphate (34 or
      136 mg/kg) as superphosphate, and with and without addition of Hebeloma arenosa
      inoculum. Shoot and total dry weights of mycorrhizal seedlings grown in soil
      unamended with P were greater than those for nonmycorrhizal seedlings grown in
      the same soil, but less than the dry weights of seedlings grown in soil amended
      with middle to high levels of P. Mycorrhizal infection was inhibited at the
      highest level of P amendment. (31)P nuclear magnetic resonance spectra of intact
      mycorrhizal roots showed the presence of two dominant peaks, orthophosphate (Pi)
      and polyphosphate (polyP). The polyP peak was absent in spectra of nonmycorrhizal
      roots. The ratio for areas under the two peaks, Pi/polyP, was 1.8 for mycorrhizal
      roots grown in both unamended soil and soil that had received middle levels of
      superphosphate. Apparently, the fungus strongly mediates the supply of phosphate
      to the tree through the production of polyP, even at growth-limiting levels of
      soil P, and regulates compartmentalization of P in the mycorrhizal roots.

PMID- 16653051
TI  - Mechanism of the Decline in Vacuolar H -ATPase Activity in Mung Bean Hypocotyls
      during Chilling.
AB  - The mechanism responsible for the decrease in the activity of vacuolar H(+) 
      ATPase during chilling was investigated in seedlings of mung bean (Vigna
      radiata). After chilling at 0 degrees C for 3 d, the activity of vacuolar H(+) 
      ATPase, calculated on the basis of membrane protein, decreased to 47% of the
      original value. Of the nine subunits of the ATPase, the specific contents of at
      least six subunits, of 68, 57, 44, 38, 37, and 32 kD, decreased in vacuolar
      membranes after chilling, as judged by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. These subunits were released by treatment with chaotropic anions
      such as thiocyanate. The level of the 16-kD subunit did not change. Immunoblot
      analyses showed the decrease in the levels of the subunits of 68, 57, and 32 kD.
      Furthermore, the specific activity of the ATPase purified from chilled hypocotyls
      was two-thirds of that of the enzyme from nonchilled seedlings, and the enzyme
      from chilled tissue retained only a small amount of the 32-kD subunit. These
      results suggest that a selective release of the peripheral subunits of the ATPase
      from the membrane and a partial degradation of the ATPase complex may occur in
      vivo during chilling.

PMID- 16653052
TI  - Common identity of substrate binding subunit of vacuolar h-translocating
      inorganic pyrophosphatase of higher plant cells.
AB  - There have been conflicting reports in the literature concerning the polypeptide
      composition of the vacuolar H(+)-translocating inorganic pyrophosphatase
      (tonoplast H(+)-PPase) of plant cells. The major subunit(s) of the enzyme have
      been attributed to polypeptides of relative molecular weight (M(r)) 64,500 (Beta
      vulgaris), 67,000 (Beta vulgaris), 73,000 (Vigna radiata), and 37,000 to 45,000
      (Zea mays). Here, we reconcile these differences to show, through the combined
      application of independent purification, affinity-labeling, sequencing, and
      immunological procedures, that the major polypeptide associated with the H(+)
      PPase from all of these organisms, and Arabidopsis thaliana, corresponds to the
      same moiety. The principal polypeptide components of the H(+)-PPase purified from
      Beta and Vigna by independent procedures have similar apparent subunit masses
      when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) under identical conditions (M(r(Beta)) = 64,500; M(r(Vigna)) = 66,000) and
      exhibit identical kinetics of irreversible inhibition and ligand-modified
      labeling by [(14)C]-N-ethylmaleimide. Similarly, the M(r) 64,500 and 67,000
      polypeptides isolated from Beta by independent methods (cf. C.J. Britten, J.C.
      Turner, P.A. Rea [1989] FEBS Lett 256: 200-206 versus V. Sarafian and R.J. Poole
      [1989] Plant Physiol 91: 34-38) are indistinguishable: the two polypeptides
      comigrate when electrophoresed under the same conditions and yield tryptic
      fragments with identical overlapping sequences. Because both the N-terminal
      sequence of the M(r) 66,000 subunit of the H(+)-PPase isolated from Vigna and the
      direct sequence data from Beta align precisely with the deduced amino acid
      sequence of cDNAs encoding the H(+)-PPase of Arabidopsis, all three enzymes are
      inferred to be highly conserved structurally. Accordingly, immunoblots of
      membranes prepared from Arabidopsis, Beta, Vigna, and Zea, probed with antibody
      affinity purified against the magnesium inorganic pyrophosphate-binding, M(r)
      66,000 polypeptide of Vigna, reveal a single immunoreactive band at M(r) 64,500
      to 67,000 in all four preparations. The M(r) 66,000 polypeptide of Zea membranes
      is, however, prone to proteolysis during membrane fractionation and selective
      aggregation during sample denaturation for SDS-PAGE. The anomalous M(r) 37,000 to
      45,000 subunit pattern previously ascribed to the H(+)-PPase from Zea (A. Chanson
      and P.E. Pilet [1989] Plant Physiol 90: 934-938) is attributed to loss of the
      M(r) 66,000 subunit and the appearance of polypeptide fragments of M(r) 44,700
      and 39,000 through the combined effects of sample aggregation before SDS-PAGE and
      proteolysis, respectively. It is, therefore, concluded that the substrate-binding
      subunit of the tonoplast H(+)-PPase has a common identity in all four organisms.

PMID- 16653053
TI  - Effects of Water-Deficit Stress on Photosynthesis, Its Components and Component
      Limitations, and on Water Use Efficiency in Wheat (Triticum aestivum L.).
AB  - It is of theoretical as well as practical interest to identify the components of
      the photosynthetic machinery that govern variability in photosynthesis rate (A)
      and water-use efficiency (WUE), and to define the extent by which the component
      processes limit A and WUE during developing water-deficit stress. For that
      purpose, leaf exchange of CO(2) and H(2)O was determined in two growth-chamber
      grown wheat cultivars (Triticum aestivum L. cv TAM W-101 and cv Sturdy), and the
      capacity of A was determined and broken down into carboxylation efficiency
      (c.e.), light- and CO(2)-saturated A, and stomatal conductance (g(s)) components.
      The limitations on A measured at ambient CO(2) concentration (A(350)) were
      estimated. No cultivar difference was observed when A(350) was plotted versus
      leaf water potential (Psi(w)). Light- and CO(2)-saturated A, c.e., and g(s)
      decreased with decreasing leaf Psi(w), but of the corresponding photosynthesis
      limitations only those caused by insufficient c.e. and g(s) increased. Thus,
      reduced stomatal aperture and Calvin cycle activity, but not electron
      transport/photophosphorylation, appeared to be major reasons for drought stress
      induced inhibition of A(350). WUE measured as A(350)/g(s) first increased with
      stomatal closure down to a g(s) of about 0.25 mol H(2)O m(-2) s(-1) (Psi(w) = 
      1.6 MPa). However, it was predicted that A(350)/g(s) would decrease with more
      severe stress due to inhibition of c.e.

PMID- 16653054
TI  - Induction of cold stability of microtubules in cultured tobacco cells.
AB  - In suspension-cultured tobacco (Nicotiana tabacum) cells, we have often
      encountered cold-stable microtubules (MTs). The cold-stable MTs were found in the
      pelleted fraction of tobacco cell homogenates. These cold-stable MTs were shown
      to be accompanied by unidentified filamentous structures that extended along part
      of their length. However, during the early hours in culture such cold-stable MTs
      were never observed. They were detectable from 120 h after the beginning of
      subculture and then their numbers increased gradually. The number of cells with
      cold-stable MTs eventually accounted for more than 95% of the total population of
      cells at the stationary phase of culture. The rapid loss of cold stability of MTs
      occurred when such cells were transferred to fresh medium for subculture.
      However, if the fresh medium was supplemented with once-used medium, the cold
      stability of MTs was retained. The active agent in the medium appeared to be of
      low molecular weight and to be heat resistant. A similar activity was detected in
      a pectin hydrolyzate. When an inhibitor of protein kinase, either 6
      dimethylaminopurine or staurosporin, was added to the cells at an early stage of
      culture, when cold-stable MTs were normally completely absent, most cells
      acquired cold-stable MTs. It appears that acquisition or loss of cold stability
      of MTs in tobacco cells is regulated by the action of a kinase/phosphatase or a
      phosphorylation/dephosphorylation system on some MT protein(s), such as a cold
      stabilizer of MTs, some unidentified MT-associated filamentous structure, or even
      tubulin itself.

PMID- 16653055
TI  - Alterations in Nicotiana tabacum L. cv Xanthi Cell Membrane Function following
      Treatment with an Ethylene Biosynthesis-Inducing Endoxylanase.
AB  - An ethylene biosynthesis-inducing xylanase (EIX) produced by the fungus
      Trichoderma viride elicited enhanced ethylene biosynthesis and leakage of
      potassium and other cellular components when applied to leaf disks of tobacco
      (Nicotiana tabacum L. cv Xanthi). Suspension-cultured cells of Xanthi tobacco
      responded to EIX by rapid efflux of potassium, uptake of calcium, alkalization of
      the medium, inhibition of ethylene biosynthesis, and increased leakage of
      cellular components. EIX-treated cell suspensions released 1-aminocyclopropane-1
      carboxylate (ACC) into the surrounding medium, resulting in a reduction of
      cellular pools of ACC. The responses of both cell suspensions and leaf disks were
      inhibited (50-80%) by the preincubation of the tissues with the calcium channel
      blocker La(3+). High concentrations of EGTA inhibited the alkalization of the
      medium by cell suspensions responding to EIX, but EGTA alone caused extensive
      loss of K(+) and ACC and inhibited ethylene biosynthesis by tobacco cells.
      Alterations in membrane function appear to be important in the mode of action of
      EIX in Xanthi cells.

PMID- 16653056
TI  - Purification of maize pollen exines and analysis of associated proteins.
AB  - Zea mays (maize) pollen exines have been purified with the use of differential
      centrifugation and sucrose gradients, followed by mild detergent and high salt
      treatment. The final exine fraction is highly purified from other organelles and
      subcellular structures as assayed by transmission electron microscopy. Using
      mature maize pollen as the starting material, 0.2 to 0.3% of the total pollen
      protein remained associated with the exine fraction throughout the purification.
      Seven abundant sodium dodecyl sulfate-extractable proteins are detected by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis in the final fraction. Amino
      acid analysis reveals that one of the proteins contains a substantial amount of
      hydroxyproline, a characteristic of some primary cell wall proteins. The amino
      acid composition of the 25-kD protein strongly implies that it is an
      arabinogalactan protein. When exines are purified from earlier pollen
      developmental stages, a subset of the proteins found in the mature pollen exine
      is seen.

PMID- 16653057
TI  - Iron Reduction and Trans Plasma Membrane Electron Transfer in the Yeast
      Saccharomyces cerevisiae.
AB  - The ferri-reductase activity of whole cells of Saccharomyces cerevisiae (washed
      free from the growth medium) was markedly increased 3 to 6 h after transferring
      the cells from a complete growth medium (preculture) to an iron-deficient growth
      medium (culture). This increase was prevented by the presence of iron, copper,
      excess oxygen, or other oxidative agents in the culture medium. The cells with
      increased ferri-reductase activity had a higher reduced glutathione content and a
      higher capacity to expose exofacial sulfhydryl groups. Plasma membranes purified
      from those cells exhibited a higher reduced nicotinamide adenine phosphate
      (NADPH)-dependent ferri-reductase specific activity. However, the intracellular
      levels of NADPH, NADH, and certain organic acids of the tricarboxylic acids cycle
      were unchanged, and the activity of NADPH-generating enzymes was not increased.
      Addition of Fe(III)-EDTA to iron-deprived and iron-rich cells in resting
      suspension resulted in a decrease in intracellular reduced glutathione in the
      case of iron-deprived cells and in an increase in organic acids and a sudden
      oxidation of NADH in both types of cells. The depolarizing effect of Fe(3+) was
      more pronounced in iron-rich cells. The metabolic pathways that may be involved
      in regulating the trans-plasma membrane electron transfer in yeast are discussed.

PMID- 16653058
TI  - Basic Endochitinases Are Major Proteins in Castanea sativa Cotyledons.
AB  - Basic endochitinases are abundant proteins in Castanea sativa Mill. cotyledons.
      Three basic chitinases were purified with molecular masses of 25, 26, and 32 kD
      (Ch1, Ch2, and Ch3) and with isoelectric points between 8 and 9.5. Antibodies
      raised against Ch1 cross-reacted with Ch2 and Ch3. However, Ch3 showed
      differences when compared with the other two enzymes, especially in its higher
      cysteine content. The size, amino acid composition, and N-terminal sequence of
      Ch1 indicate that it is a class II endochitinase and, therefore, has no cysteine
      rich hevein domain. Ch1 inhibits the growth of the fungus Trichoderma viride. The
      biological role of these endochitinases is discussed.

PMID- 16653059
TI  - Association of Carbonic Anhydrase Activity with Carboxysomes Isolated from the
      Cyanobacterium Synechococcus PCC7942.
AB  - The development of a simple method for the isolation of purified carboxysomes
      from the cyanobacterium Synechococcus PCC7942 has made it possible to identify a
      specific and inducible, intracellular carbonic anhydrase (CA) activity that is
      strongly associated with carboxysomes. This was shown, in part, through enzyme
      recovery experiments that indicated that a clear majority of a CA activity that
      is sensitive to the CA inhibitor ethoxyzolamide (I(50) = 4 mum) copurifies with a
      majority of the cell's ribulose-1,5-bisphosphate carboxylase/oxygenase activity
      in a highly purified pelletable fraction. Electron microscopy of this pelletable
      fraction revealed the presence of carboxysomes that were physically intact.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of carboxysome
      proteins showed that the large and small subunits of ribulose-1,5-bisphosphate
      carbosylase/oxygenase were clearly prominent and that several other minor
      proteins could be distinguished. The specific location of this carboxysomal CA
      activity is further reinforced by the finding that a previously isolated high
      CO(2)-requiring mutant, Type II/No. 68 (G.D. Price, M.R. Badger [1989] Plant
      Physiol 91: 514-525), displayed a 30-fold reduction in carboxysome-associated CA
      activity when tested under optimal conditions. Carboxysomal CA has the unusual
      property of being inactivated by dithiothreitol. The enzyme also requires 20 mm
      Mg(2+) (as MgSO(4)) for near maximum activity; other divalent cations, such as
      Ca(2+) and Mn(2+), also stimulate carboxysomal CA activity, but to a lesser
      extent than Mg(2+). Results are discussed in relation to the role of carboxysomes
      in the CO(2)-concentrating mechanism in cyanobacteria and the role that
      carboxysomal CA activity appears to play in this process.

PMID- 16653060
TI  - Isolation of a Putative Carboxysomal Carbonic Anhydrase Gene from the
      Cyanobacterium Synechococcus PCC7942.
AB  - The Type II mutants of the cyanobacterium Synechococcus PCC7942 (G.D. Price, M.R.
      Badger [1989] Plant Physiol 91: 514-525) are able to accumulate a large pool of
      inorganic carbon inside the cell, but are unable to utilize it for CO(2)
      fixation, resulting in a high CO(2)-requiring phenotype. We have isolated a 3.5
      kb BamHI clone (pT2) that complements the Type II mutants, and complementation
      analysis with DNA subclones indicated that the complementing region was located
      in the 0.75-kb XhoI-Bg/II fragment. This same region hybridized to the
      chloroplastic carbonic anhydrase (CA) gene from spinach on Southern blots and to
      a mRNA of approximate 1 kb on northern blots. Restriction mapping and sequence
      analysis revealed that pT2 is the same as a genomic clone (pBM3.8) that
      complements another high CO(2)-requiring (temperature sensitive) mutant, C3P-O
      (E. Suzuki, H. Fukuzawa, S. Miyachi [1991] Mol Gen Genet 226: 401-408). Recently,
      a 272-amino acid open reading frame showing 22% homology with pea and spinach
      chloroplast CA genes was identified in clone pBM3.8 (H. Fukuzawa, E. Suzuki, Y.
      Komukal, S. Miyachi [1992] Proc Natl Acad Sci USA 89: 4437-4441). CA activity was
      detected in Escherichia coli cells transformed with subclones of pT2 (pT2-A and
      pT2-A1) containing the HindIII-Bg/II fragment, and the expressed CA has
      properties similar to those of the CA activity associated with carboxysomes
      purified from Synechococcus PCC7942 (G.D. Price, J.R. Coleman, M.R. Badger [1992]
      Plant Physiol 100: 784-793). Therefore, it is reasonable to conclude that the
      HindIII-Bg/II fragment codes for the carboxysomal CA gene product. The result is
      discussed in the context of the role that carboxysomal CA plays in the operation
      of the CO(2)-concentrating mechanism in cyanobacteria.

PMID- 16653061
TI  - Developmental expression of tomato heat-shock cognate protein 80.
AB  - Heat-shock protein 80 (HSP80) is a major heat-shock protein induced in yeast and
      animals both by heat shock and by specific developmental events. In plants, a
      heat-shock-induced HSP80 cDNA has been described, although no information
      concerning developmental regulation of HSP80 genes is available. We have
      characterized a tomato (Lycopersicon esculentum) gene encoding a typical HSP80
      protein. This gene, called HSC80, is interrupted by two introns, 995 and 109 bp
      long. Northern blot analyses and in situ RNA hybridization show that HSC80 mRNA
      is abundant in shoot and root apices and in fertilized ovaries up to 6 d
      postanthesis but is rare in mature leaves. Heat shock increased mRNA levels in
      mature leaves but only 3-fold. Developmental regulation of the HSC80 gene was
      confirmed by fusing 2 kb of its 5' region to the beta-glucuronidase reporter gene
      and introducing the chimeric gene into tomatoes. The roots of transformants
      showed high beta-glucuronidase expression in the apex and in lateral root
      primordia but not in mature tissue. Expression in the shoot was up to 10-fold
      higher in the apex than in mature leaves. Thus, HSC80 is preferentially expressed
      in shoot and root apices during normal development.

PMID- 16653062
TI  - Synthesis and Accumulation of Calmodulin in Suspension Cultures of Carrot (Daucus
      carota L.) : Evidence for Posttranslational Control of Calmodulin Expression.
AB  - The expression of calmodulin mRNA and protein were measured during a growth cycle
      of carrot (Daucus carota L.) cells grown in suspension culture. A full-length
      carrot calmodulin cDNA clone isolated from a lambdagt10 library was used to
      measure steady-state calmodulin mRNA levels. During the exponential phase of
      culture growth when mitotic activity and oxidative respiration rates were
      maximal, calmodulin mRNA levels were 4- to 5-fold higher than they were during
      the later stages of culture growth, when respiration rates were lower and growth
      was primarily by cell expansion. Net calmodulin polypeptide synthesis, as
      measured by pulse-labeling in vivo with [(35)S]methionine, paralleled the changes
      in calmodulin steady-state mRNA level during culture growth. As a consequence,
      net calmodulin polypeptide synthesis declined 5- to 10-fold during the later
      stages of culture growth. The qualitative spectrum of polypeptides synthesized
      and accumulated by the carrot cells during the course of a culture cycle,
      however, remained largely unchanged. Calmodulin polypeptide levels, in contrast
      to its net synthesis, remained relatively constant during the exponential phases
      of the culture growth cycle and increased during the later stages of culture
      growth. Our data are consistent with increased calmodulin polypeptide turnover
      associated with periods of rapid cell proliferation and high levels of
      respiration.

PMID- 16653063
TI  - Normal growth of transgenic tobacco plants in the absence of cytosolic pyruvate
      kinase.
AB  - The coding sequence of the cytosolic isozyme of potato tuber pyruvate kinase (PK)
      was attached to the transit peptide of the small subunit of pea ribulose-1,5
      bisphosphate carboxylase oxygenase and placed under the control of the
      cauliflower mosaic virus 35S promoter. This construct was transformed into
      Nicotiana tabacum. Unexpectedly, two primary transformants were recovered in
      which PK activity in leaves was greatly reduced. The reduction in PK activity
      appeared to result from the complete absence of the cytosolic form of the enzyme
      (PK(c)). In addition, no PK(c) could be detected on western blots of leaf
      extracts. Metabolite analyses indicated that the levels of phosphoenolpyruvate
      are substantially higher in PK(c)-deficient leaves than in wild-type leaves,
      consistent with a block in glycolysis at the step catalyzed by PK. PK(c)
      deficiency in the leaves does not appear to adversely affect plant growth.
      Analysis of progeny indicates that PK(c) deficiency is a heritable trait. The
      leaves of PK(c)-deficient transformants have normal rates of photosynthetic O(2)
      evolution and respiratory O(2) consumption, indicating that these plants are
      using alternative pathways to bypass PK.

PMID- 16653064
TI  - Putrescine N-Methyltransferase in Cultured Roots of Hyoscyamus albus: n
      Butylamine as a Potent Inhibitor of the Transferase both in Vitro and in Vivo.
AB  - Biosynthesis of tropane alkaloids is thought to proceed by way of the diamine
      putrescine, followed by its methylation by putrescine N-methyltransferase (PMT;
      EC 2.1.1.53). High PMT activities were found in branch roots and/or cultured
      roots of several solanaceous plants. PMT was partially purified and characterized
      from cultured roots of Hyoscyamus albus that contain hyoscyamine as the main
      alkaloid. Initial velocity studies and product inhibition patterns of PMT are
      consistent with an ordered bi-bi mechanism, in which the K(m) values for
      putrescine and S-adenosyl-l-methionine are 277 and 203 mum, respectively, and the
      K(i) value for S-adenosyl-l-homocysteine is 110 mum. PMT efficiently N-methylated
      amines that have at least two amino groups separated by three or four methylene
      groups. Monoamines were good competitive inhibitors of PMT, among which n
      butylamine, cyclohexylamine, and exo-2-aminonorbornane were most inhibitory, with
      respective K(i) values of 11.0, 9.1, and 10.0 mum. When n-butylamine was fed to
      root cultures of H. albus, the alkamine intermediates (tropinone, tropine, and
      pseudotropine) drastically decreased at 1 mm of the exogenous monoamine, and the
      hyoscyamine content decreased by 52% at 6 mm, whereas the contents of 6beta
      hydroxyhyoscyamine and scopolamine did not change. Free and conjugated forms of
      polyamines were also measured. The n-butylamine treatment caused a large increase
      in the putrescine content (especially in the conjugated pool), and the spermine
      content also increased slightly, whereas the spermidine content decreased
      slightly. The increase in the putrescine pool size (approximately 40 nmol/mg dry
      weight) was large enough to account for the decrease in the total alkaloid pool
      size. Similar results were also obtained in root cultures of Datura stramonium.
      These studies further support the role of PMT as the first committed enzyme
      specific to alkaloid biosynthesis.

PMID- 16653065
TI  - Two Tropinone Reductases with Distinct Stereospecificities from Cultured Roots of
      Hyoscyamus niger.
AB  - Tropinone is an alkamine intermediate at the branch point of biosynthetic
      pathways leading to various tropane alkaloids. Two stereospecifically distinct
      NADPH-dependent oxidoreductases, TR-I and TR-II, which, respectively, reduce
      tropinone to 3alpha-hydroxytropane (tropine) and 3beta-hydroxytropane (psi
      tropine), were detected mainly in the root of tropane alkaloid-producing plants
      but not in nonproducing cultured root. Both reductases were purified to near
      homogeneity from cultured root of Hyoscyamus niger and characterized. The TR-I
      reaction was reversible, whereas the TR-II reaction was essentially irreversible,
      reduction of the ketone being highly favored over oxidation of the alcohol psi
      tropine. Marked differences were found between the two reductase in their
      affinities for tropinone substrate and in the effects of amino acid modification
      reagents. Some differences in substrate specificity were apparent. For example, N
      propyl-4-piperidone was reduced by TR-II but not by TR-I. Conversely, 3
      quinuclidinone and 8-thiabicyclo[3,2,1]octane-3-one were accepted as substrates
      by TR-I but hardly at all by TR-II. Both enzymes were shown to be class B
      oxidoreductases, which transfer the pro-S hydrogen of NAD(P)H to their
      substrates. Possible roles of these tropinone reductases in alkaloid biosynthesis
      are discussed.

PMID- 16653066
TI  - Release of Small Polyuronides from Nitella Cell Walls during Ionic Exchange.
AB  - Mono-divalent ion exchange in isolated cell walls of Nitella flexilis (L.) Ag.
      induces a marked loss of wall polymers and a decrease in the wall cationic
      exchange capacity. These data correlate with the replacement in the walls of
      adsorbed Mn(2+) by Na(+) ions. Boiling wall samples in methanol for 1 h or
      keeping the ionic solutions chilled to 4 degrees C does not inhibit the cell wall
      polymer leakage but modifies the kinetics both of the ionic exchange and of the
      released polymers. These data are more compatible with physical rather than
      enzymic induced processes. The extracted polymers in the successively renewed
      NaCl solutions initially belong to the wall protein and pectin fractions and
      mainly to pectic fractions subsequently. Determination of the average degree of
      polymerization shows that the average molecular size of the lost acidic
      polysaccharides increases with extraction time up an average polymerization
      degree of 25. Enzyme-linked immunosorbent assay inhibition tests show the
      presence of homopolymer blocks equal to or higher than 10 in the released polymer
      fragments. Compositional analysis of released polysaccharides suggests that the
      pectin lost by action of monovalent ions was largely composed of
      rhamnogalacturonans whose acidic residue fraction is approximately 60% in
      association with galactose chains. Small quantities of glucuronylated xylans are
      also found.

PMID- 16653067
TI  - Effect of stem water content on sap flow from dormant maple and butternut stems:
      induction of sap flow in butternut.
AB  - Sap flow from excised maple stems collected over the winter (1986/87) was
      correlated with stem water content. Stem water content was high in the fall
      (>0.80) and decreased rapidly during 2 weeks of continuous freezing temperatures
      in late winter (<0.60). Exudation of sap from stem segments subjected to
      freeze/thaw cycles was small (<10 mL/kg) in the fall, but substantial exudation
      (45-50 mL/kg) occurred following the decline in water content. These observations
      are consistent with Milburn's and O'Malley's models (J.A. Milburn, P.E.R.
      O'Malley [1984] Can J Bot 62: 2101-2106; P.E.R. O'Malley, J.A. Milburn [1983] Can
      J Bot 61:3100-3106) of sap absorption into gas-filled fibers during freezing.
      Exudation volume was increased 200 to 300% in maple stems originally at high
      water content (>0.80) after perfusion with sucrose and dehydration at -12 degrees
      C. Sap flow was also induced in butternut stem segments after the same treatment.
      Thus, sap flow may not be unique to maples. Sap flow could not be increased in
      stem segments dehydrated at 4 degrees C. Migration of water molecules from small
      ice crystals in fibers to larger crystals in vessels while stems were frozen may
      account for increase exudation after dehydration at -12 degrees C. This would
      result in preferential dehydration of fibers and a distribution of gas and sap
      favorable for stem-based sap flow.

PMID- 16653068
TI  - Characterization of vacuolar calcium-binding proteins.
AB  - The vacuole plays a major structural and biochemical role in the higher plant
      cell. Among the most studied properties of the vacuole have been transport
      activities. One important aspect of vacuolar function is its participation in the
      regulation of cytosolic calcium levels. To identify the molecular entities
      involved in calcium regulation, a study of vacuole-associated, calcium-binding
      proteins (CaBs) was initiated. A competition assay was used, and it was observed
      that the majority of the total cellular membrane-associated, calcium-binding
      activity resided in low-density fractions enriched in vacuole membranes. Much of
      that calcium-binding activity was inactivated by a 0.5 m KI wash, and of the
      remaining activity, 77% was estimated to be peripherally associated with vacuolar
      membranes, whereas 23% was integrally associated with the vacuolar membrane.
      Calcium-ligand blots were used, and four major CaBs, with apparent molecular
      masses of 64, 58, 55, and 42 kD, were detected in purified vacuole membrane
      fractions. Two of these, the 58- and the 55-kD polypeptide, also appear to be
      present in significant amounts in endoplasmic reticulum-enriched fractions.
      However, the 64- and the 42-kD polypeptide are found primarily in vacuolar
      fractions. It is interesting that expression of the 42-kD polypeptide appears to
      be restricted to the heavily vacuolated cortical tissues (i.e. it is not found in
      vascular tissues). The localization of CaBs in the vacuole is consistent with the
      presence of calcium uptake (H(+)/Ca(2+) antiport) and release mechanisms
      (inositol trisphosphate sensitive) on vacuolar membranes. These vacuole
      associated CaBs, which may play a role in calcium buffering, together with the
      calcium transport systems, could mediate the vacuolar component of cellular
      calcium homeostasis.

PMID- 16653069
TI  - Cytochrome p-450-dependent hydroxylation of lauric Acid at the subterminal
      position and oxidation of unsaturated analogs in wheat microsomes.
AB  - Microsomes from etiolated wheat (Triticum aestivum L. cv Etoile de Choisy) shoots
      catalyzed the reduced nicotinamide adenine dinucleotide phosphate-dependent
      hydroxylation of lauric acid predominantly at the subterminal or (omega-1)
      position (65%). Minor amounts of 10-hydroxy- (31%) and 9-hydroxylaurate (4%) were
      also formed. The reaction was catalyzed by cytochrome P-450, since enzyme
      activity was strongly inhibited by tetcyclacis, carbon monoxide, and antibodies
      against NADPH-cytochrome c (P-450)-reductase. The apparent K(m) for lauric acid
      was estimated to be 8.5 +/- 2.0 mum. Seed treatment with the safener naphthalic
      acid anhydride or treatment of seedlings with phenobarbital increased cytochrome
      P-450 content and lauric acid hydroxylase (LAH) activity of the microsomes. A
      combination of both treatments further stimulated LAH activity. A series of
      radiolabeled unsaturated lauric acid analogs (8-, 9-, 10-, and 11-dodecenoic
      acids) was used to explore the regioselectivity and catalytic capabilities of
      induced wheat microsomes. It has been found that wheat microsomes catalyzed the
      reduced nicotinamide adenine dinucleotide phosphate-dependent epoxidation of sp2
      carbons concurrently with hydroxylation at saturated positions. The
      regioselectivity of oxidation of the unsaturated substrates and that of lauric
      acid were similar. Preincubation of wheat microsomes with reduced nicotinamide
      adenine dinucleotide phosphate and 11-dodecenoic acid resulted in a partial loss
      of LAH activity.

PMID- 16653070
TI  - Aryl hydroxylation of the herbicide diclofop by a wheat cytochrome p-450
      monooxygenase : substrate specificity and physiological activity.
AB  - Wheat (Triticum aestivum L. cv Etoile de Choisy) microsomes catalyzed the
      cytochrome P-450-dependent oxidation of the herbicide diclofop to three hydroxy
      diclofop isomers. Hydroxylation was predominant at carbon 4, with migration of
      chlorine to carbon 5 (67%) and carbon 3 (25%). The 2,4-dichloro-5-hydroxy isomer
      was identified as a minor reaction product (8%). Substrate-specificity studies
      showed that the activity was not inhibited or was weakly inhibited by a range of
      xenobiotic or physiological cytochrome P-450 substrates, with the exception of
      lauric acid. Wheat microsomes also catalyze the metabolism of the herbicides
      chlorsulfuron, chlortoluron, and 2,4-dichlorophenoxyacetic acid and of the model
      substrate ethoxycoumarin, as well as the hydroxylation of the endogenous
      substrates cinnamic and lauric acids. Treatments of wheat seedlings with
      phenobarbital or the safener naphthalic acid anhydride enhanced the cytochrome P
      450 content of the microsomes and all related activities except that of cinnamic
      acid 4-hydroxylase, which was reduced. The stimulation patterns of diclofop aryl
      hydroxylase and lauric acid hydroxylase were similar, in contrast with the other
      activities tested. Lauric acid inhibited competitively (K(i) = 9 mum) the
      oxidation of diclofop and reciprocally. The similarity of diclofop aryl
      hydroxylase and lauric acid hydroxylase was further investigated by alternative
      substrate kinetics, autocatalytic inactivation, and computer-aided molecular
      modelisation studies, and the results suggest that both reactions are catalyzed
      by the same cytochrome P-450 isozyme.

PMID- 16653071
TI  - Tolerance to imidazolinone herbicides in wheat.
AB  - An imidazolinone-tolerant wheat (Triticum aestivum L. em Thell) mutant in the
      winter wheat cultivar Fidel has been identified and characterized. The mutant was
      isolated from a population derived through seed mutagenesis of the variety with
      an aqueous solution containing sodium azide. Imidazolinone-tolerant wheat
      seedlings were selected from the M(2) generation of the population in the
      presence of imazethapyr herbicide and identified as herbicide-insensitive
      individuals. The trait is inherited as a single semidominant gene and confers
      high levels of tolerance to imazethapyr. Acetohydroxyacid synthase activity in
      extracts from imidazolinonetolerant plants was less inhibited by imazethapyr than
      the enzyme from the wild type. The herbicide-tolerant plants have a completely
      normal phenotype and display no negative effects on growth and yield in either
      the absence or presence of imazethapyr.

PMID- 16653072
TI  - beta-Amylases in Cereals : A Study of the Maize beta-Amylase System.
AB  - beta-Amylase of maize (Zea mays L.) caryopses was studied during development and
      germination by means of enzymic, electrophoretic, and immunochemical techniques.
      beta-Amylase activity increased during caryopsis development to a maximum value
      at the beginning of the water content plateau (at this stage the enzyme was
      located primarily within the pericarp) and then decreased. Almost no beta-amylase
      (activity or antigen) was found in either free or bound forms in the mature maize
      caryopsis. The activity increased again during seedling growth and reached much
      higher values. Both the aleurone layer (to a major extent) and the scutellum
      produced and secreted beta-amylase during germination, the secretion being
      stimulated by Ca(2+). No posttranslational modification of the enzyme was
      detected during germination. The molecular specific activity of the enzyme
      remained unchanged during the observed periods, indicating that the regulation of
      the activity is based essentially on protein turnover. The enzyme from developing
      and germinating caryopses was found to be identical in terms of antigenicity,
      isoelectric point, and molecular mass to the beta-amylases extracted from the
      roots and the leaves of the maize seedling. The maize beta-amylase resembles in
      all respects the ubiquitous beta-amylase described for rye and wheat, whereas the
      major beta-amylase of those cereals appears to be lacking in the maize caryopsis.

PMID- 16653073
TI  - Expression of the Yeast Delta-9 Fatty Acid Desaturase in Nicotiana tabacum.
AB  - To examine the processes of plant cytoplasmic fatty acid desaturation and
      glycerolipid biosynthesis, the protein coding sequence of the endoplasmic
      reticulum cytochrome b(5)-dependent, Delta-9 fatty acid desaturase gene from
      Saccharomyces cerevisiae was introduced into Nicotiana tabacum via Agrobacterium
      transformation. All transformed plants expressing the yeast gene at the mRNA
      level exhibited an approximately 10-fold increase in the levels of palmitoleic
      acid (16:1) in leaf tissue. This fatty acid species is found in very low levels
      (less than 2%) in wild-type plants. These results indicate that the yeast
      desaturase can function in plants, presumably by using a leaf microsomal
      cytochrome b(5)-mediated electron transport system. Lipid analysis demonstrated
      that the overproduced 16:1 is incorporated into most of the major polar lipid
      classes, including the cytoplasmically produced "eukaryotic" fraction of the
      chloroplast galactolipids. 16:1 was not found, however, in phosphatidyl glycerol,
      which is considered to be produced almost exclusively in the chloroplast. Despite
      these changes in membrane lipid composition, no obvious phenotypic differences
      were apparent in the transformed plants. Positional analysis shows that the
      cytoplasmically produced 16:1 is found primarily in the sn-2 position of
      phosphatidylcholine, phosphatidylethanolamine, monogalactosyldiacylglycerol, and
      digalactosyldiacylglycerol. The positional data suggest that the sn-2
      acyltransferases responsible for the "eukaryotic" arrangement of 16- and 18-
      carbon fatty acids in glycerolipids are selective for unsaturated fatty acids
      rather than chain length.

PMID- 16653074
TI  - Flavonols stimulate development, germination, and tube growth of tobacco pollen.
AB  - The effect of anther-derived substances on pollen function was studied using
      pollen produced by in vitro culture of immature pollen of tobacco (Nicotiana
      tabacum L.) and petunia (Petunia hybrida). Addition of conditioned medium
      consisting of diffusates from in situ matured pollen strongly increased pollen
      germination frequency and pollen tube growth, as well as seed set after in situ
      pollination. Thin-layer chromatography and depletion of phenolic substances by
      Dowex treatment indicated that flavonols are present in the diffusate and may be
      the active compounds. When added to the germination medium, flavonols (quercetin,
      kaempferol, myricetin) but not other flavonoids strongly promoted pollen
      germination frequency and pollen tube growth in vitro. The best results were
      obtained at very low concentrations of the flavonols (0.15-1.5 mum), indicating a
      signaling function. The same compounds were also effective when added during
      pollen development in vitro.

PMID- 16653075
TI  - Light regulation of leaf mitochondrial pyruvate dehydrogenase complex : role of
      photorespiratory carbon metabolism.
AB  - Light-dependent inactivation of mitochondrial pyruvate dehydrogenase complex
      (mtPDC) in pea (Pisum sativum L.) leaves was further characterized, and this
      phenomenon was extended to several monocot and dicot species. The light-dependent
      inactivation of mtPDC in vivo was rapidly reversed in the dark, even after
      prolonged illumination. The mtPDC can be efficiently cycled through the
      inactivated-reactivated status by rapid light-dark cycling. Light-dependent
      inactivation of mtPDC was shown to be suppressed by inhibitors of
      photorespiratory carbon metabolism, including 2-pyridylhydroxymethane sulfonate,
      isonicotinic acid hydrazide, and aminoacetonitrile, and by an inhibitor of
      photosynthesis, 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Glycine fed to pea leaf
      strips in the dark yielded partially inactivated leaf mtPDC, and this
      inactivation was blocked by inhibitors of glycine oxidation. It is concluded that
      the photorespiratory glycine to serine conversion that occurs in C(3) leaf
      mitochondria can provide the NADH to drive oxidative phosphorylation and
      subsequent inactivation of mtPDC. Glycine oxidation also produces ammonium ion,
      which has been shown to enhance the inactivation of mtPDC in vitro by stimulating
      the pyruvate dehydrogenase kinase that catalyzes the phosphorylation
      (inactivation) of the mtPDC. Thus, light-dependent, photorespiration-stimulated
      inactivation of the mtPDC can regulate carbon entry into the Krebs cycle during
      C(3) photosynthesis.

PMID- 16653076
TI  - Characterization of a Cold-Regulated Wheat Gene Related to Arabidopsis cor47.
AB  - The cDNA clone pWG1 represents a gene, designated cor39, from Triticum aestivum
      L. cv Winoka (a winter wheat) that is related to a cold-regulated Arabidopsis
      thaliana L. (Heyn) gene, cor47. In vitro transcription/translation experiments in
      conjunction with DNA sequence analysis indicated that cor39 encodes a hydrophilic
      polypeptide of 39 kD (isoelectric point of 7.5), designated COR39. The
      polypeptide is composed primarily of two sequences, each of which is repeated six
      times. One sequence, which is lysine rich, occurs in COR47 (the polypeptide
      encoded by Arabidopsis cor47) and group II LEA proteins, polypeptides
      hypothesized to have roles in desiccation and drought tolerance (J. Baker, C.
      Steele, L. Dure III [1988] Plant Mol Biol 11: 277-291). The second sequence,
      which is glycine rich, occurs in some, but not all, group II LEA proteins.
      Southern analysis indicated that wheat has a number of loci related to cor39.
      Transcripts of about 3.3, 1.5, and 0.8 kb that hybridize with cor39 were found to
      accumulate in leaf, root, and crown tissues of cold-acclimated plants; they
      accumulated rapidly in response to low temperature and returned quickly to low
      levels when plants were returned to normal growth temperature. Transcripts
      hybridizing with cor39 were present at relatively high levels in wheat seeds and
      accumulated in plants in response to exogenous application of ABA and water
      stress. The similarities in expression of wheat and Arabidopsis cor genes and
      possible functional relationships among COR39, COR47, and LEA proteins are
      discussed.

PMID- 16653077
TI  - Regulation of plant Fatty Acid biosynthesis : analysis of acyl-coenzyme a and
      acyl-acyl carrier protein substrate pools in spinach and pea chloroplasts.
AB  - In previous work (D. Post-Beittenmiller, J.G. Jaworski, J.B. Ohlrogge [1991] J
      Biol Chem 266: 1858-1865), the in vivo acyl-acyl carrier protein (ACP) pools were
      measured in spinach (Spinacia oleracea) leaves and changes in their levels were
      compared to changes in the rates of fatty acid biosynthesis. To further examine
      the pools of substrates and cofactors for fatty acid biosynthesis and to evaluate
      metabolic regulation of this pathway, we have now examined the coenzyme A (CoA)
      and short chain acyl-CoA pools, including acetyl- and malonyl-CoA, in isolated
      spinach and pea (Pisum sativum) chloroplasts. In addition, the relationships of
      the acetyl- and malonyl-CoA pools to the acetyl- and malonyl-ACP pools have been
      evaluated. These studies have led to the following conclusions: (a) Essentially
      all of the CoA (31-54 mum) in chloroplasts freshly isolated from light-grown
      spinach leaves or pea seedling was in the form of acetyl-CoA. (b) Chloroplasts
      contain at least 77% of the total leaf acetyl-CoA, based on comparison of acetyl
      CoA levels in chloroplasts and total leaf. (c) CoA-SH was not detected either in
      freshly isolated chloroplasts or in incubated chloroplasts and is, therefore,
      less than 2 mum in the stroma. (d) The malonyl-CoA:ACP transacylase reaction is
      near equilibrium in both light- and dark-incubated chloroplasts, whereas the
      acetyl-CoA:ACP transacylase reaction is far from equilibrium in light-incubated
      chloroplasts. However, the acetyl-CoA:ACP transacylase reaction comes nearer to
      equilibrium when chloroplasts are incubated in the dark. (e) Malonyl-CoA and -ACP
      could be detected in isolated chloroplasts only during light incubations, and
      increased with increased rates of fatty acid biosynthesis. In contrast, both
      acetyl-CoA and acetyl-ACP were detectable in the absence of fatty acid
      biosynthesis, and acetyl-ACP decreased with increased rates of fatty acid
      biosynthesis. Together these data have provided direct in situ evidence that
      acetyl-CoA carboxylase plays a regulatory role in chloroplast fatty acid
      biosynthesis.

PMID- 16653078
TI  - The Role of Acyl Lipids in Reconstitution of Lipid-Depleted Light-Harvesting
      Complex II from Cold-Hardened and Nonhardened Rye.
AB  - The role of acyl lipids in the in vitro stabilization of the oligomeric form of
      light-harvesting complex II of winter rye (Secale cereale L. cv Muskateer) grown
      at 5 or 20 degrees C was investigated. Purified light-harvesting complex II was
      enzymically delipidated to various extents by treatment with the following
      lipolytic enzymes: phospholipase C, phospholipase A(2), and galactolipase.
      Complete removal of phosphatidylcholine had no effect on the stability of the
      oligomeric form, whereas the removal of phosphatidylcholine plus
      phosphatidylglycerol caused a decrease in the ratio of oligomeric:monomeric forms
      from 1.86 +/- 0.17 to 0.85 +/- 0.17 and 3.51 +/- 0.82 to 0.81 +/- 0.29 for
      purified cold-hardened and nonhardened light-harvesting complex II, respectively,
      with no change in free pigment content. Incubation of delipidated cold-hardened
      or nonhardened light-harvesting complex with purified thylakoid
      phosphatidylglycerol containing trans-Delta(3)-hexadecenoic acid resulted in 48%
      reconstitution of the oligomeric form on a total chlorophyll basis with an
      oligomer:monomer of about 1.90. Incubation in the presence of di- 16:0 or di-
      18:1 phosphatidylglycerol, phosphatidylcholine, monogalactosyldiacylglyceride, or
      digalactosyldiacylglyceride caused no oligomerization, but rather a further
      destabilization of the monomeric form. These lipid-dependent structural changes
      were correlated with significant changes in the 77K fluorescence emission spectra
      for purified light-harvesting complex II. We conclude that the stabilization of
      the supramolecular organization of light-harvesting complex II from rye is
      specifically dependent upon molecular species of phosphatidylglycerol containing
      trans-Delta(3)-hexadecenoic acid.

PMID- 16653079
TI  - Degree of C(4) Photosynthesis in C(4) and C(3)-C(4)Flaveria Species and Their
      Hybrids : I. CO(2) Assimilation and Metabolism and Activities of
      Phosphoenolpyruvate Carboxylase and NADP-Malic Enzyme.
AB  - The degree of C(4) photosynthesis was assessed in four hybrids among C(4), C(4)
      like, and C(3)-C(4) species in the genus Flaveria using (14)C labeling, CO(2)
      exchange, (13)C discrimination, and C(4) enzyme activities. The hybrids
      incorporated from 57 to 88% of the (14)C assimilated in a 10-s exposure into C(4)
      acids compared with 26% for the C(3)-C(4) species Flaveria linearis, 91% for the
      C(4) species Flaveria trinervia, and 87% for the C(4)-like Flaveria brownii.
      Those plants with high percentages of (14)C initially fixed into C(4) acids also
      metabolized the C(4) acids quickly, and the percentage of (14)C in 3
      phosphoglyceric acid plus sugar phosphates increased for at least a 30-s exposure
      to (12)CO(2). This indicated a high degree of coordination between the carbon
      accumulation and reduction phases of the C(4) and C(3) cycles. Synthesis and
      metabolism of C(4) acids by the species and their hybrids were highly and
      linearly correlated with discrimination against (13)C. The relationship of (13)C
      discrimination or (14)C metabolism to O(2) inhibition of photosynthesis was
      curvilinear, changing more rapidly at C(4)-like values of (14)C metabolism and
      (13)C discrimination. Incorporation of initial (14)C into C(4) acids showed a
      biphasic increase with increased activities of phosphoenolpyruvate carboxylase
      and NADP-malic enzyme (steep at low activities), but turnover of C(4) acids was
      linearly related to NADP-malic enzyme activity. Several other traits were closely
      related to the in vitro activity of NADP-malic enzyme but not phosphoenolpyruvate
      carboxylase. The data indicate that the hybrids have variable degrees of C(4)
      photosynthesis but that the carbon accumulation and reduction portions of the
      C(4) and C(3) cycles are well coordinated.

PMID- 16653080
TI  - Degree of C(4) Photosynthesis in C(4) and C(3)-C(4)Flaveria Species and Their
      Hybrids : II. Inhibition of Apparent Photosynthesis by a Phosphoenolpyruvate
      Carboxylase Inhibitor.
AB  - Hybrids have been made between species of Flaveria exhibiting varying levels of
      C(4) photosynthesis. The degree of C(4) photosynthesis expressed in four
      interspecific hybrids (Flaveria trinervia [C(4)] x F. linearis [C(3)-C(4)], F.
      brownii [C(4)-like] x F. linearis, and two three-species hybrids from F.
      trinervia x [F. brownii x F. linearis]) was estimated by inhibiting
      phosphoenolpyruvate carboxylase in vivo with 3,3-dichloro-2
      dihydroxyphosphinoylmethyl-2-propenoate (DCDP). The inhibitor was fed to detached
      leaves at a concentration of 4 mm, and apparent photosynthesis was measured at
      atmospheric levels of CO(2) and at 20 and 210 mL L(-1) of O(2). Photosynthesis at
      210 mL L(-1) of O(2) was inhibited 32% by DCDP in F. linearis, by 60% in F.
      brownii, and by 87% in F. trinervia. Inhibition in the hybrids ranged from 38 to
      52%. The inhibition of photosynthesis by 210 mL L(-1) of O(2) was increased when
      DCDP was used, except in the C(4) species, F. trinervia, in which photosynthesis
      was insensitive to O(2). Except for F. trinervia, control plants with less O(2)
      sensitivity (more C(4)-like) exhibited a progressively greater change in O(2)
      inhibition of photosynthesis when treated with DCDP. This increased O(2)
      inhibition probably resulted from decreased CO(2) concentrations in bundle sheath
      cells due to inhibition of phosphoenolpyruvate carboxylase. The inhibition of
      photosynthesis by DCDP is concluded to underestimate the degree of C(4)
      photosynthesis in the interspecific hybrids because increased direct assimilation
      of atmospheric CO(2) by ribulose bisphosphate carboxylase may compensate for
      inhibition of phosphoenolpyruvate carboxylase.

PMID- 16653081
TI  - A Role for the Surrounding Fruit Tissues in Preventing the Germination of Tomato
      (Lycopersicon esculentum) Seeds : A Consideration of the Osmotic Environment and
      Abscisic Acid.
AB  - During tomato seed development the endogenous abscisic acid (ABA) concentration
      peaks at about 50 d after pollination (DAP) and then declines at later stages (60
      70 DAP) of maturation. The ABA concentration in the sheath tissue immediately
      surrounding the seed increases with time of development, whereas that of the
      locule declines. The water contents of the seed and fruit tissues are similar
      during early development (20-30 DAP), but decline in the seed tissues between 30
      and 40 DAP. The water potential and the osmotic potential of the embryo are lower
      than that of the locular tissue after 35 DAP also. Seeds removed from the fruit
      at 30, 35, and 60 DAP and placed ex situ on 35 and 60 DAP sheath and locular
      tissue are prevented from germinating. Development of 30 DAP seeds is maintained
      or promoted by the ex situ fruit tissue with which they are in contact. Their
      germination is inhibited until subsequent transfer to water, and germination is
      normal, i.e. by radicle protrusion, and viable seedlings are produced, compared
      with 30 DAP seeds transferred directly to water; more of these seeds germinate,
      but by hypocotyl extension, and seedling viability is very poor. Isolated seeds
      at 35 and 60 DAP re-placed in contact with fruit tissues only germinate when
      transferred to water after 7 d. At 30 DAP, isolated seeds are insensitive to ABA
      at physiological concentrations in that they germinate as if on water, albeit by
      hypocotyl extension. At higher concentrations germination occurs by radicle
      protrusion. Osmoticum prevents germination, but there is some recovery upon
      subsequent transfer to water. Seeds at 35 DAP are very sensitive to ABA and
      exhibit little or no germination, even upon transfer to water. The response of
      the isolated seeds to osmoticum more closely approximates that to incubation on
      the ex situ fruit tissues than does their response to ABA. This is also the case
      for isolated 60 DAP seeds, whose germination is not prevented by ABA, but only by
      the osmoticum; these seeds are inhibited when in contact with ex situ fruit
      tissues also. It is proposed that the osmotic environment within the tissues of
      the tomato fruit plays a greater role than endogenous ABA in preventing
      precocious germination of the developing seeds.

PMID- 16653082
TI  - Plastid DNA in developing maize endosperm : genome structure, methylation, and
      transcript accumulation patterns.
AB  - Amyloplasts in storage organs such as maize (Zea mays L.) endosperm are plastid
      derived, nonphotosynthetic, starch-accumulating organelles. This study was
      initiated to characterize the plastid genome in maize endosperm cells containing
      differentiated amyloplasts and to determine whether plastid genes are transcribed
      during the period of amyloplast biogenesis in endosperm development. Four cosmid
      clones representing the total sequence diversity of the maize plastid genome were
      hybridized to restriction digests of total cellular DNA from isolated 16-day-old
      endosperms. The hybridization patterns indicated that the plastid DNA present in
      endosperm tissue was indistinguishable from that in leaf total DNA. Methylation
      of maize endosperm amyloplast DNA or leaf chloroplast DNA was not detected with
      the methylation-sensitive enzymes HpaII and EcoRII. Transcripts homologous to the
      17 specific plastid DNA BamHI fragments tested were detectable in total RNA
      prepared from 16-day-old endosperm tissue. Compared with leaf transcripts, the
      abundance of endosperm transcripts was substantially lower for transcripts
      detected by 12 different BamHI fragments and was similar or relatively higher for
      some transcripts homologous to five BamHi fragments. Transcripts homologous to
      genes for plastid ribosomal small subunit proteins 7 and 12 on fragments 10 and
      23 and to an open reading frame on fragment 14 accumulated primarily as
      unprocessed or partially processed species in endosperm RNA. The demonstration
      that maize endosperm cells contain an intact, transcriptionally active plastid
      genome indicates that plastid genes could contribute to amyloplast biogenesis,
      although no transcripts unique to endosperm were identified.

PMID- 16653083
TI  - Autophosphorylation of the pea mitochondrial heat-shock protein homolog.
AB  - Highly purified mitochondria isolated from 14-day-old pea (Pisum sativum L., cv
      Little Marvel) seedlings contain a homolog of the 70,000 molecular weight heat
      shock protein. The amount of this heat-shock cognate (Hsc70) was not reduced by
      limited proteolysis of intact mitochondria or by preparation of mitoplasts,
      indicating that the protein is located within the matrix compartment. Pea
      mitochondrial Hsc70 binds to immobilized ATP and reacts on western blots with
      anti-tomato Hsc70 antiserum. When a mitochondrial matrix fraction was incubated
      with [gamma-(32)P]ATP, there was phosphorylation of Hsc70. The extent of
      phosphorylation was increased by including calcium chloride in the reactions.
      Phospho amino acid analysis of purified mitochondrial Hsc70, phosphorylated in
      the calcium-stimulated reaction, revealed only phosphothreonine. Pea
      mitochondrial Hsc70, purified by a combination of ATP-agarose affinity
      chromatography and gel permeation chromatography, was labeled when incubated with
      ATP plus calcium, suggesting autophosphorylation rather than phosphorylation by
      an associated kinase. In analogy to mammalian cells and yeast, it is likely that
      mitochondrial Hsc70 acts as a molecular chaperone, and it is possible that
      phosphorylation plays a role in chaperone function.

PMID- 16653084
TI  - Effects of cycling temperatures on fiber metabolism in cultured cotton ovules.
AB  - The effects of temperature on rates of cellulose synthesis, respiration, and long
      term glucose uptake were investigated using cultured cotton ovules (Gossypium
      hirsutum L. cv Acala SJ1). Ovules were cultured either at constant 34 degrees C
      or under cycling temperatures (12 h at 34 degrees C/12 h at 15-40 degrees C).
      Rates of respiration and cellulose synthesis at various temperatures were
      determined on day 21 during the stage of secondary wall synthesis by feeding
      cultured ovules with [(14)C]glucose. Respiration increased between 18 and
      approximately 34 degrees C, then remained constant up to 40 degrees C. In
      contrast, the rate of cellulose synthesis increased above 18 degrees C, reached a
      plateau between about 28 and 37 degrees C, and then decreased at 40 degrees C.
      Therefore, the optimum temperature for rapid and metabolically efficient
      cellulose synthesis in Acala SJ1 is near 28 degrees C. In ovules cycled to 15
      degrees C, respiration recovered to the control rate immediately upon rewarming
      to 34 degrees C, but the rate of cellulose synthesis did not fully recover for
      several hours. These data indicate that cellulose synthesis and respiration
      respond differently to cool temperatures. The long-term uptake of glucose, which
      is the carbon source in the culture medium, increased as the low temperature in
      the cycle increased between 15 and 28 degrees C. However, glucose uptake did not
      increase in cultures grown constantly at 34 degrees C compared to those cycled at
      34/28 degrees C. These observations are consistent with previous observations on
      the responses of fiber elongation and weight gain to cycling temperatures in
      vitro and in the field.

PMID- 16653085
TI  - Isoprene emission rate and intercellular isoprene concentration as influenced by
      stomatal distribution and conductance.
AB  - Isoprene emission in relation to stomatal distribution and conductance was
      determined for the hypostomatous species, aspen and white oak, and the
      amphistomatous species, cottonwood. For aspen and oak, isoprene emission from the
      adaxial (nonstomatal) surface was <2% of that from the abaxial (stomatal)
      surface, even when stomata were closed by addition of abscisic acid (ABA). When
      treated with ABA, the total flux rate of isoprene emission from leaves of these
      two hypostomatous species was unchanged, despite decreases in stomatal
      conductance of over 90%. The lack of control over isoprene emission rate by
      stomatal conductance, despite the apparent movement of isoprene through the
      stomatal pores, was due to increases in the intercellular isoprene concentration
      that compensated for the decreased stomatal conductance and restored the
      equilibrium between the isoprene synthesis rate and emission rate. This
      relationship was demonstrated by (a) an experiment in which the decrease in the
      internal isoprene pool following the imposition of darkness took longer in the
      presence of ABA than in its absence, and (b) direct measurements of the internal
      isoprene concentration through vacuum extraction, which revealed substantially
      higher values in the presence of ABA than in its absence. In the amphistomatous
      species, cottonwood, isoprene was emitted from both surfaces and addition of ABA
      caused an increase in isoprene emission from one surface coupled with a decrease
      from the other surface. The specific surface exhibiting an increase varied among
      leaves, with some leaves exhibiting an increase from the adaxial surface and
      other leaves from the abaxial surface. We interpret this as indicating nonuniform
      stomatal closure with concomitant emission of isoprene at the greatest rate from
      the surface with the highest stomatal conductance. We also observed an increase
      in the total isoprene emission rate from cottonwood leaves following treatment
      with ABA. We interpret this as indicating a stimulation of isoprene synthesis in
      response to ABA or stomatal closure, with unknown cause.

PMID- 16653086
TI  - Effect of cellulose synthesis inhibition on growth and the integration of
      xyloglucan into pea internode cell walls.
AB  - 2,6-Dichlorobenzonitrile (DCB, 100 mum) inhibited by 80 to 85% the incorporation
      of [(3)H]glucose into cellulose in stem segments of etiolated pea (Pisum sativum)
      seedlings. The inhibition lasted for at least 24 h. In the period 1 to 4 h after
      the excision of the segments, DCB did not influence elongation in the presence or
      absence of 2,4-dichlorophenoxyacetic acid (2,4-D). However, during the period 1
      to 24 h after excision, DCB enhanced endogenous and 2,4-D-stimulated elongation
      by 65 and 34%, respectively. DCB did not affect the incorporation of (3)H from
      [(3)H]arabinose into xyloglucan, and did not change the ability of the
      [(3)H]xyloglucan formed in vivo to bind strongly to the cell wall. Therefore, at
      least 80 to 85% of newly synthesized cellulose was excess to the requirements for
      tight wall binding of newly synthesized xyloglucan. This conflicts with the
      hypothesis that xyloglucan is held in the cell wall solely by direct hydrogen
      bonding to the surfaces of cellulosic microfibrils.

PMID- 16653087
TI  - Molecular Analysis and Heterologous Expression of an Inducible Cytochrome P-450
      Protein from Periwinkle (Catharanthus roseus L.).
AB  - We screened cDNA libraries from periwinkle (Catharanthus roseus) cell cultures
      induced for indole alkaloid synthesis and selected clones for induced cytochrome
      P-450 (P-450) proteins by differential hybridization, size of the hybridizing
      mRNA, and presence of amino acid motifs conserved in many P-450 families. Four
      cDNAs satisfying these criteria were analyzed in detail. They were grouped in two
      classes (pCros1, pCros2) that represented two closely related genes of a new P
      450 family designated CYP72. Antiserum against a cDNA fusion protein
      overexpressed in Escherichia coli recognized in C. roseus a protein band of 56
      kD. Quantification of western blots showed that it represented 1.5 +/- 0.5 and 6
      +/- 1 mug/mg of protein in the membranes from noninduced and induced cells,
      respectively, and analysis of the total P-450 content suggested that the cDNA
      encoded protein was one of the dominant P-450 proteins. The pathway to indole
      alkaloids contains two known P-450 enzymes, geraniol-10-hydroxylase (GE10H) and
      nerol-10-hydroxylase (NE10H). The induction kinetics of the cloned P-450 protein
      and of GE10H activity were similar, but those of NE10H were different. Western
      blots with membranes from other plants suggested that P-450 CYP72 is specific for
      C. roseus and other plants with GE10H activity. A tentative assignment of CYP72
      as GE10H is discussed. The cDNA was recloned for expression in Saccharomyces
      cerevisiae, and the presence of the protein was demonstrated by western blots.
      Assays for GE10H failed to detect enzyme activity, and the same negative result
      was obtained for NE10H and other P-450 enzymes that are present in C. roseus.

PMID- 16653088
TI  - Modifying starch biosynthesis with transgenes in potatoes.

PMID- 16653089
TI  - Measurements of the Engagement of Cyanide-Resistant Respiration in the
      Crassulacean Acid Metabolism Plant Kalanchoe daigremontiana with the Use of On
      Line Oxygen Isotope Discrimination.
AB  - Discrimination against (18)O during dark respiration in tissues of Kalanchoe
      daigremontiana, Medicago sativa, and Glycine max was measured using an on-line
      system that enabled direct measurements of the oxygen fractionation of samples in
      a gas-phase leaf disk electrode unit. Discrimination factors for cytochrome
      pathway respiration were 18.6 to 19.8%(o) for all tissues. However,
      discrimination in cyanide-resistant respiration was significantly higher in green
      tissues (30.4-31.2%(o)) compared with nongreen tissues (25.3-25.9%(o)). Using
      these discrimination factors, the partitioning of electron transport to these
      pathways was calculated from measurements of discrimination in the absence of
      inhibitors. Changes in flux through the alternative pathway were measured during
      the light and dark phases of Crassulacean acid metabolism in leaf disks of K.
      daigremontiana. The flux of electrons through the alternative pathway was higher
      during deacidification than during the other phases of Crassulacean acid
      metabolism. The increase in alternative pathway electron flux accounted for all
      of the increased respiration in the light phase. Despite this increase,
      simultaneous measurements of malate concentration and respiratory flux confirm
      that only a small proportion of the total malate decarboxylation occurs in the
      mitochondria.

PMID- 16653090
TI  - Flow cytometry of spinach chloroplasts : determination of intactness and lectin
      binding properties of the envelope and the thylakoid membranes.
AB  - Intact spinach (Spinacia oleracea) chloroplasts, thylakoid membranes, and inside
      out or right-side-out thylakoid vesicles have been characterized by flow
      cytometry with respect to forward angle light scatter, right angle light scatter,
      and chlorophyll fluorescence. Analysis of intact chloroplasts with respect to
      forward light scatter and the chlorophyll fluorescence parameter revealed the
      presence of truly "intact" and "disrupted" chloroplasts. The forward light
      scatter parameter, normally considered to reflect object size, was instead found
      to reflect the particle density. One essential advantage of flow cytometry is
      that additional parameters such as Ricinus communis agglutinin (linked to
      fluorescein isothiocyanate) fluorescence can be determined through logical
      conditions placed on bit-maps, amounting to an analytical purification procedure.
      In the present case, chloroplast subpopulations with fully preserved envelopes,
      thylakoid membrane, and inside-out or right-side-out thylakoid membranes vesicles
      can be distinguished. Flow cytometry is also a useful tool to address the
      question of availability of glycosyl moities on the membrane surfaces if one
      keeps in mind that organelle-to-organelle interactions could be partially
      mediated through a recognition process. A high specific binding of R. communis
      agglutinin and peanut lectin to the chloroplast envelope was detected. This
      showed that galactose residues were exposed and accessible to specific lectins on
      the chloroplast surface. No exposed glucose, fucose, or mannose residues could be
      detected by the appropriate lectins. Ricin binding to the intact chloroplasts
      caused a strong aggregation. Disruption of these aggregates by resuspension or
      during passage in the flow cytometer induced partial breakage of the
      chloroplasts. Only minor binding of R. communis agglutinin and peanut lectin to
      the purified thylakoid membranes was detected; the binding was found to be low
      for both inside-out and right-side-out vesicles of the thylakoid membranes.

PMID- 16653091
TI  - Constitutive Transcription and Stable RNA Accumulation in Plastids during the
      Conversion of Chloroplasts to Chromoplasts in Ripening Tomato Fruits.
AB  - The size distribution of plastid transcripts during chromoplast differentiation
      in ripening tomato (Lycopersicon esculentum L.) fruits was determined using
      northern blot analysis. Hybridization of total cellular RNA from leaves and
      fruits with several tobacco chloroplast DNA probes showed distinct transcript
      patterns in chloroplasts and chromoplasts. We also compared transcriptional rates
      by probing immobilized DNA fragments of small size (representing about 85% of the
      plastid genome) with run-on transcripts from tomato plastids. The relative rates
      of transcription of the various DNA regions were very similar in chloro- and
      chromoplasts. Parallel determination of the steady-state levels of plastid RNA
      showed no strict correlation between synthesis rate and RNA accumulation.
      Differences in the relative abundance of transcripts between chloro- and
      chromoplasts were not very pronounced and were limited to a small number of
      genes. The results indicate that the conversion of chloroplasts to chromoplasts
      at the onset of tomato fruit ripening proceeds with no important variations in
      the relative transcription rates and with only moderate changes in the relative
      stability of plastid-encoded transcripts.

PMID- 16653092
TI  - Induction of UDP-Glucose:Salicylic Acid Glucosyltransferase in Oat Roots.
AB  - A UDP-glucose:salicylic acid 3-O-glucosyltransferase (EC 2.4.1.35) (GTase) from
      oat (Avena sativa L. cv Dal) root extracts was assayed in vitro using
      [(14)C]salicylic acid (SA) and an ion exchange column to separate SA from beta
      glucosylsalicylic acid. The GTase, present at a very low constitutive level, was
      inducible to 23 times the constitutive level. When excised roots were exposed to
      SA at pH 6.5, the specific activity of the enzyme increased within 1.5 h, peaked
      after 8 to 10 h, and then declined. The increase in specific activity depended on
      the concentration of SA in the induction medium. Among 16 phenolics and phenolic
      derivatives tested, GTase induction showed high specificity toward SA and
      acetylsalicylic acid. Specific activity of the enzyme was induced to higher
      levels in roots from 7-d-old seedlings than roots from younger plants. GTase
      activity was less inducible in basal compared with median or apical root
      sections. Induction of GTase activity was a result of de novo RNA and protein
      synthesis. Candidate peptides for the GTase were identified by comparison of two
      dimensional electrophoresis gels of proteins labeled with [(35)S]methionine
      during incubation of roots in the presence or the absence of SA and a gel of a
      partially purified GTase preparation.

PMID- 16653093
TI  - Ethanol-Induced Activation of ATP-Dependent Proton Extrusion in Elodea densa
      Leaves.
AB  - In Elodea densa leaves, ethanol up to 0.17 m stimulates H(+) extrusion activity.
      This effect is strictly dependent on the presence of K(+) in the medium and is
      suppressed by the presence of the plasmalemma H(+)-ATPase inhibitor vanadate.
      Stimulation of H(+) extrusion is associated with (a) a decrease in cellular ATP
      level, (b) a marked hyperpolarization of transmembrane electrical potential, and
      (c) an increase in net K(+) influx. These results suggest that ethanol-induced
      H(+) extrusion is mediated by an activation of the plasma membrane ATP-dependent,
      electrogenic proton pump. This stimulating effect is associated with an increase
      of cell sap pH and of the capacity to take up the weak acid 5,5
      dimethyloxazolidine-2,4-dione, which is interpretable as due to an increase of
      cytosolic pH. This indicates that the stimulation of H(+) extrusion by ethanol
      does not depend on a cytosolic acidification by products of ethanol metabolism.
      The similarity of the effects of ethanol and those of photosynthesis on proton
      pump activity in E. densa leaves suggests that a common metabolic situation is
      responsible for the activation of the ATP-dependent H(+)-extruding mechanism.

PMID- 16653094
TI  - Turnover of 1-aminocyclopropane-1-carboxylic Acid synthase protein in wounded
      tomato fruit tissue.
AB  - Ethylene production in plant tissues declines rapidly following induction, and
      this decline is due to a rapid decrease in the activity of 1-aminocyclopropane-1
      carboxylic acid (ACC) synthase, a key enzyme in ethylene biosynthesis. To study
      the nature of the rapid turnover of ACC synthase in vivo, proteins in wounded
      ripening tomato (Lycopersicon esculentum) fruit discs were radiolabeled with
      [(35)S]methionine, followed by a chase with nonradioactive methionine.
      Periodically, the radioactive ACC synthase was isolated with an immunoaffinity
      gel and analyzed. ACC synthase protein decayed rapidly in vivo with an apparent
      half-life of about 58 min. This value for protein turnover in vivo is similar to
      that previously reported for activity half-life in vivo and substrate-dependent
      enzyme inactivation in vitro. Carbonylcyanide-m-chlorophenylhydrazone and 2,4
      dinitrophenol, potent uncouplers of oxidative phosphorylation, strongly inhibited
      the rapid decay of ACC synthase protein in the tissue. Degradation of this enzyme
      protein was moderately inhibited by the administration of aminooxyacetic acid, a
      competitive inhibitor of ACC synthase with respect to its substrate S-adenosyl-l
      methionine, alpha,alpha'-dipyridyl, and phenylmethanesulfonyl fluoride or
      leupeptin, serine protease inhibitors. These results support the notion that the
      substrate S-adenosyl-l-methionine participates in the rapid inactivation of the
      enzyme in vivo and suggest that some ATP-dependent processes, such as the
      ubiquitin-requiring pathway, are involved in the degradation of ACC synthase
      proteins.

PMID- 16653095
TI  - Phytochrome-mediated germination of very sensitive oospores.
AB  - The light receptor and its mode of operation were studied in photosensitive
      oospores of Nitella furcata subsp. megacarpa (Allen emend. Wood). Brief pulses of
      light activated maximal germination of post-secondary dormant oospores removed
      from lake sediments. Fluence response data at 12 wavelengths were used to
      construct an action spectrum for germination. The shape of the action spectrum
      with its maximum at 669 nm provides evidence for the involvement of phytochrome.
      Germination was induced with photon fluences that established as little as 0.01%
      of the phytochrome in the far red-absorbing form, which suggests that phytochrome
      was operating in the very low-fluence response mode. The functioning of
      phytochrome in the very low-fluence response mode in Nitella is similar to that
      in higher plants.

PMID- 16653096
TI  - Characterization of Vacuolar Malate and K Channels under Physiological
      Conditions.
AB  - Patch-clamp techniques were employed to study the electrical properties of
      vacuoles from sugar beet (Beta vulgaris) cell suspensions at physiological
      concentrations of cytoplasmic Ca(2+). Vacuoles exposed to K(+) malate revealed
      the activation of instantaneous and time-dependent outward currents by positive
      membrane potentials. Negative potentials induced only instantaneous inward
      currents. The time-dependent outward currents were 10 times more selective for
      malate than for K(+) and were completely blocked by zinc. Vacuoles exposed to KCl
      developed instantaneous currents when polarized to positive or negative membrane
      potentials. The time-dependent outward channels could serve as the route for the
      movement of malate into the vacuole, whereas K(+) could move through the time
      independent inward and outward channels.

PMID- 16653097
TI  - Photoacclimation in the Red Alga Porphyridium cruentum: Changes in Photosynthetic
      Enzymes, Electron Carriers, and Light-Saturated Rate of Photosynthesis as a
      Function of Irradiance and Spectral Quality.
AB  - Acclimation of the photosynthetic apparatus to changes in the light environment
      was studied in the unicellular red alga Porphyridium cruentum (American Type
      Culture Collection No. 50161). Absolute or relative amounts of four
      photosynthetic enzymes and electron carriers were measured, and the data were
      compared with earlier observations on light-harvesting components (F.X.
      Cunningham, Jr., R.J. Dennenberg, L. Mustardy, P.A. Jursinic, E. Gantt [1989]
      Plant Physiol 91: 1179-1187; F.X. Cunningham, Jr., R.J. Dennenberg, P.A.
      Jursinic, E. Gantt [1990] Plant Physiol 93: 888-895) and with measurements of
      photosynthetic capacity. P(max), the light-saturated rate of photosynthesis on a
      chlorophyll (Chl) basis, increased more than 4-fold with increase in growth
      irradiance from 6 to 280 mueinsteins.m(-2).s(-1). Amounts of ferredoxin-NADP(+)
      reductase, ribulose-1,5-bisphosphate carboxylase, and cytochrome f increased in
      parallel with P(max), whereas numbers of the light-harvesting complexes
      (photosystem [PS] I, PSII, and phycobilisomes) changed little, and ATP synthase
      increased 7-fold relative to Chl. The calculated minimal turnover time for PSII
      under the highest irradiance, 5 ms, was thus about 4-fold faster than that
      calculated for cultures grown under the lowest irradiance (19 ms). A change in
      the spectral composition of the growth light (irradiance kept constant at 15
      mueinsteins.m(-2).s(-1)) from green (absorbed predominantly by the phycobilisome
      antenna of PSII) to red (absorbed primarily by the Chl antenna of PSI) had little
      effect on the amounts of ribulose-1,5-bisphosphate carboxylase, ATP synthase, and
      phycobilisomes on a Chl, protein, or thylakoid area basis. However, the number of
      PSI centers declined by 40%, cytochrome f increased by 40%, and both PSII and
      ferredoxin-NADP(+) reductase increased approximately 3-fold on a thylakoid area
      basis. The substantial increase in ferredoxin-NADP(+) reductase under PSI light
      is inconsistent with a PSI-mediated reduction of NADP as the sole function of
      this enzyme. Our results demonstrate a high degree of plasticity in content and
      composition of thylakoid membranes of P. cruentum.

PMID- 16653098
TI  - Plasma membrane vesicles from source and sink leaves : changes in solute
      transport and polypeptide composition.
AB  - Plasma membrane vesicles (PMVs) were prepared by phase partitioning from
      microsomal fractions of either sink or source leaves of sugar beet (Beta vulgaris
      L.). The purity, the internal volume, the sidedness, and the sealingness of PMVs
      prepared from sink leaves did not differ from those measured with PMVs from
      source leaves. Yet, in response to an imposed proton motive force, PMVs from
      source leaves accumulated about 4-fold more sucrose than PMVs from sink leaves.
      The developmental stage did not affect the uptake of glucose and valine in PMVs
      prepared from leaf tissues. It was concluded that the sink/source transition is
      accompanied either by the incorporation into the plasma membrane of leaf cells of
      proteins mediating proton-sucrose cotransport, or by their activation. N
      ethylmaleimide and a polyclonal ascitic fluid directed against the 42-kD region
      of the plasma membrane containing a putative sucrose carrier inhibited the uptake
      of sucrose in PMVs from source leaves, but not in PMVs from sink leaves. Sodium
      dodecyl sulfate gel electrophoresis and western blot suggested that the 42
      polypeptide was more abundant in the PMVs from source leaves than in the PMVs
      from sink leaves.

PMID- 16653099
TI  - Threonine Overproduction in Transgenic Tobacco Plants Expressing a Mutant
      Desensitized Aspartate Kinase of Escherichia coli.
AB  - In higher plants, the synthesis of the essential amino acid threonine is
      regulated primarily by the sensitivity of the first enzyme in its biosynthetic
      pathway, aspartate kinase, to feedback inhibition by threonine and lysine. We
      aimed to study the potential of increasing threonine accumulation in plants by
      means of genetic engineering. This was addressed by the expression of a mutant,
      desensitized aspartate kinase derived from Escherichia coli either in the
      cytoplasm or in the chloroplasts of transgenic tobacco (Nicotiana Tabacum cv
      Samsun NN) plants. Both types of transgenic plants exhibited a significant
      overproduction of free threonine. However, threonine accumulation was higher in
      plants expressing the bacterial enzyme in the chloroplast, indicating that
      compartmentalization of aspartate kinase within this organelle was important,
      although not essential. Threonine overproduction in leaves was positively
      correlated with the level of the desensitized enzyme. Transgenic plants
      expressing the highest leaf aspartate kinase activity also exhibited a slight
      increase in the levels of free lysine and isoleucine, both of which share a
      common biosynthetic pathway with threonine, but showed no significant change in
      the level of other free amino acids. The present study proposes a new molecular
      biological approach to increase the limiting content of threonine in higher
      plants.

PMID- 16653100
TI  - Expression of the Large ATP Synthase Gene Cluster in Spinach Plastids during
      Light-Induced Development.
AB  - The large ATP synthase gene cluster in spinach (Spinacia oleracea) plastids
      encodes four of the six chloroplast-encoded ATP synthase subunits. Expression of
      this cluster was examined to determine its response to light-induced plastid
      development. Spinach plastid transcripts were isolated from etiolated tissues,
      etiolated tissues exposed to 24 h of light, young (1-3 cm) leaves, and mature (8
      10 cm) leaves. Transcript levels were examined from each developmental stage as a
      function of either the quantity of total RNA or gene dosage. The relative
      transcriptional activity of this gene cluster at each of the four developmental
      stages was also investigated. The stability of these transcripts was deduced by
      comparing the transcriptional activity with steady-state transcript levels.
      During the initial 24 h of light-induced development of an etioplast to a
      chloroplast, transcription decreases in conjunction with increased transcript
      stability. Transcriptional activity of this cluster per genome then increases
      between the 24-h and young stages, with a concomitant decrease in the stability
      of the transcripts. As the young chloroplast matures, the transcripts from this
      cluster again become markedly more stable, and the transcription of this set of
      genes declines. Therefore, the regulation of the expression of this cluster is
      dependent upon a complex interaction between transcriptional and
      posttranscriptional factors throughout light-induced plastid development.

PMID- 16653101
TI  - Differential Expression and Sequence Analysis of Ribosomal Protein Genes Induced
      in Stolon Tips of Potato (Solanum tuberosum L.) during the Early Stages of
      Tuberization.
AB  - cDNA clones of two genes, TUBS19 and TUBL7, which show a 15- to 20-fold increase
      in transcript level in the stolon tip during the early stages of tuberization,
      have been isolated by differential screening. These genes are also expressed in
      leaves, stems, and roots, and the expression pattern in these organs changes on
      tuberization. Southern analysis shows that there are similar sequences in the
      genome of nontuberizing wild-type potato species Solanum brevidens and in
      Lycopersicon esculentum (tomato). Sequence analysis reveals a high degree of
      similarity between the TUBS19 cDNA and the eukaryotic S19 ribosomal protein gene.
      TUBL7 cDNA shows similarity to another eukaryotic ribosomal protein gene, L7.

PMID- 16653102
TI  - Chloroplast Dedifferentiation in Mechanically Isolated Asparagus Cells during
      Culture Initiation.
AB  - Mechanically isolated asparagus (Asparagus officinalis) mesophyll cells
      dedifferentiate and divide when cultured in the dark in a medium containing
      sucrose. A strong correlation was observed between the onset of cell division and
      a loss of photosynthetic capacity. For the first 8 to 9 d of culture, there was
      no change in chloroplast size or morphology. However, following this period, the
      chloroplasts divided to form smaller proplastid-like structures. The gross
      chlorophyll content of the cell population did not change, suggesting that the
      loss of photosynthetic potential was not by senescence. Northern analysis showed
      that mRNA of the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase
      was undetectable within 1 d postisolation, which was quicker than in dark-treated
      plants. The mRNA of the large subunit of ribulose 1,5-bisphosphate
      carboxylase/oxygenase decreased to low levels within 2 d of cell isolation. Both
      the large and small subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase
      protein showed a gradual reduction in abundance, falling to basal levels by days
      6 to 7, which coincided with the onset of rapid cell division. A similar trend
      was observed with chloroplast rRNA molecules, which decreased to basal levels by
      day 6 in culture.

PMID- 16653103
TI  - Regulation of Gibberellin Biosynthesis in Gibberella fujikuroi.
AB  - Gibberellin production by Gibberella fujikuroi started only after the nitrogen
      source was depleted and ceased upon its renewal. Nitrogen repression of
      gibberellin biosynthesis is not an indirect effect of the growth arrest that
      follows the depletion of an essential nutrient because gibberellins were not
      produced upon depletion of phosphate. Mycelia produced gibberellins when
      suspended in a glucose solution. Production ceased some time after depletion of
      glucose and resumed upon its readdition. Under certain conditions, the
      gibberellin production rate was inversely proportional to the glucose
      concentrations. The specific regulation of gibberellin biosynthesis by the
      nitrogen source imposes a revision of the concept that gibberellins are secondary
      metabolites whose production is triggered by imbalance or cessation of growth.

PMID- 16653104
TI  - Involvement of the oxidative burst in phytoalexin accumulation and the
      hypersensitive reaction.
AB  - The role of the oxidative burst, transient production of activated oxygen species
      such as H(2)O(2) and superoxide (O(2) (-)) in elicitation of phytoalexins and the
      hypersensitive reaction (HR) was investigated in white clover (Trifolium repens
      L.) and tobacco (Nicotiana tabacum L.). H(2)O(2) and O(2) (-) production was
      measured as chemiluminescence (CL) mediated by luminol, which was added to
      suspension-cultured white clover just before measurement in an out-of-coincidence
      mode scintillation counter. Maximum CL occurred between 10 and 20 min after
      addition of 0.4 x 10(8) colony-forming units/mL of incompatible Pseudomonas
      corrugata or 158 mum HgCl(2). Autoclaved P. corrugata produced a slightly higher
      response. Elicitation of cells with 25 mum HgCl(2) did not produce CL.
      Preincubation of plant cells in superoxide dismutase, which converts O(2) (-) to
      H(2)O(2), for 2 min before addition of bacteria did not significantly increase
      maximum CL levels (P >/= 0.05). Preincubation of plant cells with catalase for 2
      min before addition of bacteria prevented the increase in CL, confirming that
      H(2)O(2) is the substrate for the luminol reaction. Addition of live bacteria or
      HgCl(2) (25 and 158 mum) to white clover increased levels of the phytoalexin
      medicarpin during a 24-h period, but addition of autoclaved bacteria did not
      elicit formation of medicarpin. Preincubation of plant cells with catalase, which
      quenched the bacteria-induced oxidative burst, did not decrease phytoalexin
      accumulation. Live bacteria infiltrated into Havana 44 tobacco leaf panels
      induced development of the HR, but autoclaved bacteria did not. Incubation of
      live bacteria with superoxide dismutase and catalase before infiltration into
      tobacco leaves did not interfere with development of the HR. Tobacco leaf panels
      infiltrated with up to 158 mum HgCl(2) did not develop an HR. These results
      suggest that an oxidative burst consisting of H(2)O(2) and O(2) (-) does occur
      during these two plant defense responses, but it may not be a necessary element
      of the signaling system for HR and phytoalexin formation.

PMID- 16653105
TI  - Seed Dormancy in Red Rice : VIII. Embryo Acidification during Dormancy-Breaking
      and Subsequent Germination.
AB  - Exposure of dehulled, dormant red rice (Oryza sativa) seeds to dormancy-breaking
      treatments (10 mm sodium nitrite, 20 mm propionic acid, 30 mm methyl propionate,
      40 mm propionaldehyde, or 70 mmn-propanol) induced tissue pH acidification during
      chemical contact at least 12 h before visible germination. During chemical
      contact, the onset of embryo acidification occurred before or coincident with the
      chemical contact interval necessary for subsequent germination. Upon seed
      transfer to H(2)O following chemical contact, embryo pH also decreased coincident
      with visible germination. During this period, the percentage of germination and
      embryo pH were closely linked irrespective of the dormancy-breaking compound
      used. Therefore, tissue acidification during the breaking of seed dormancy and
      the germination process may be analogous to similar tissue pH changes associated
      with the termination of developmental arrest in other multicellular systems, such
      as brine shrimp cysts and nematode larvae.

PMID- 16653106
TI  - Cell Wall Changes in Nectarines (Prunus persica) : Solubilization and
      Depolymerization of Pectic and Neutral Polymers during Ripening and in Mealy
      Fruit.
AB  - Nectarine fruit (Prunus persica L. Batsch var nectarina [Ait] maxim) cultivar
      Fantasia were either ripened immediately after harvest at 20 degrees C or stored
      for 5 weeks at 2 degrees C prior to ripening. Fruit ripened after 5 weeks of
      storage did not soften to the same extent as normally ripened fruit, they lacked
      juice, and had a dry, mealy texture. Pectic and hemicellulosic polysaccharides
      were solubilized from the mesocarp of the fruit using phenol:acetic acid:water
      (PAW) treatment to yield PAW-soluble material and cell wall material (CWM). The
      carbohydrate composition and relative molecular weight (M(r)) of polysaccharide
      fractions released from the CWM by sequential treatment with cyclohexane-trans
      1,2-diamine tetra-acetate, 0.05 m Na(2)CO(3), 6 m guanidinium thiocyanate, and 4
      m KOH were determined. Normal ripening of nectarines resulted in solubilization
      of pectic polymers of high M(r) from CWM during the first 2 d at ripening
      temperatures. Concurrently, galactan side chains were removed from pectic
      polymers. Solubilized pectic polymers were depolymerized to lower M(r) species
      during the latter stages of ripening. Upon removal from cool storage, fruit had
      undergone some pectic polymer solubilization, and after ripening, pectins were
      not depolymerized and were of high M(r). Side chains did not appear to be removed
      from insoluble pectic polymers and branched pectins accumulated in the CWM. The
      molecular weight profiles obtained by gel filtration of the hemicellulosic
      fractions from normally ripening and mealy fruit were similar. The results
      suggest that mealiness results as a consequence of altered pectic polymer
      breakdown, including that associated with neutral side chains.

PMID- 16653107
TI  - Mode of Action Studies on a Chiral Diphenyl Ether Peroxidizing Herbicide:
      Correlation between Differential Inhibition of Protoporphyrinogen IX Oxidase
      Activity and Induction of Tetrapyrrole Accumulation by the Enantiomers.
AB  - The nitrodiphenyl ether herbicide 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2
      nitroacetophenone oxime-O-(acetic acid, methyl ester) (DPEI) induced an abnormal
      accumulation of protoporphyrin IX in darkness in the green alga Chlamydomonas
      reinhardtii, as determined by high-performance liquid chromatography and
      spectrofluorimetry. It also inhibited the increase in cell density of the alga in
      light-grown cultures with an I(50) (concentration required to decrease cell
      density increase to 50% of the noninhibited control value) of 0.16 mum. The
      relative ability of four peroxidizing diphenyl ether herbicides to cause
      tetrapyrrole accumulation in C. reinhardtii correlated qualitatively with their
      ability to inhibit the increase in cell density in light-grown cultures. The
      purified S(-) enantiomer of the optically active phthalide DPE 5-[2-chloro-4
      (trifluoromethyl)phenoxy]-3-methylphthalide (DPEIII), which has greater
      herbicidal activity than the R(+) isomer, induces a 4- to 5-fold greater
      tetrapyrrole accumulation than the R(+) isomer. The I(50) for inhibition of
      increase in cell density in light-grown cultures of C. reinhardtii by the S(-)
      isomer (0.019 mum) is less than 25% of that for the R(+) isomer. DPEIII inhibits
      protoporphyrinogen IX oxidase activity in pea (Pisum sativum) etioplast lysates,
      with the S(-) enantiomer showing considerably greater potency than the R(+)
      isomer and the racemic mixture showing a potency intermediate between the two.
      The results indicate that the site at which DPEs inhibit protoporphyrinogen IX
      oxidase shows chiral discrimination and provide further evidence for the link
      between inhibition of this enzyme, protoporphyrin IX accumulation, and the
      phytotoxicity of DPE herbicides.

PMID- 16653108
TI  - Analysis of Light-Induced Depressions of Photosynthesis in Leaves of a Wheat Crop
      during the Winter.
AB  - The photosynthetic performances of individual leaves of a wheat (Triticum
      aestivum cv Bezostaya) crop were assessed daily and throughout individual days
      during the winter when temperature and light levels were fluctuating.
      Measurements of chlorophyll fluorescence induction and the maximum quantum yield
      of O(2) evolution were made on individual leaves. Depressions in the ratio of
      variable to maximal fluorescence (F(v)/F(m)) were correlated with low
      temperatures and high light levels throughout the winter and during the course of
      individual days. Depressions in F(v)/F(m) observed in the field during the day
      were not accompanied by any significant change in the ability of photosystem II
      complexes to bind 3-(3,4-dichlorophenyl)-1-dimethyl urea, indicating that the
      depressions in F(v)/F(m) were not attributable to photodamage to the D1 protein
      of the photosystem II reaction center. Decreases in F(v)/F(m) were associated
      with increases in the rate of dissipation of excitation energy by radiationless
      decay processes and decreases in the quantum efficiency of CO(2) assimilation,
      indicative of a rapidly reversible light-induced "downregulation" of
      photosynthesis. No major changes were observed in the maximum quantum efficiency
      of O(2) evolution of leaves throughout periods of fluctuating temperature and
      light, because light-induced depressions in photosynthetic efficiency recovered
      within the time required to make these measurements.

PMID- 16653109
TI  - Modulation of Na/H Antiporter Activity by Extreme pH and Salt in the Halotolerant
      Alga Dunaliella salina.
AB  - The effect of different growth conditions on the activity of the Na(+)/H(+)
      antiporter in Dunaliella salina has been investigated. Adaptation of D. salina
      cells to ammonia at alkaline pH or to high NaCl concentrations is associated with
      a pronounced increase in the plasma membrane Na(+)/H(+) exchange activity. The
      enhanced activity is manifested both in vivo, by stimulation of Na(+) influx into
      intact cells in response to internal acidification, and in vitro, by a larger
      (22)Na accumulation in plasma membrane vesicles in response to an induced pH
      gradient. Kinetic analysis shows that the stimulation does not result from a
      change of the K(m) for Na(+) but from an increase in the V(max). In contrast,
      adaptation of cells to a high LiCl concentration (0.8 m) depresses the activity
      of the Na(+)/H(+) antiporter. Adaptation to ammonia is also associated with a
      large increase of three polypeptide bands in purified plasma membrane
      preparations, indicating that they may compose the antiporter polypeptides. These
      results suggest that adaptation to ammonia or to high salinity induces
      overproduction of the plasma membrane Na(+)/H(+) antiporter in Dunaliella.

PMID- 16653110
TI  - Regulation of key enzymes of sucrose biosynthesis in soybean leaves : effect of
      dark and light conditions and role of gibberellins and abscisic Acid.
AB  - An important part in the understanding of the regulation of carbon partitioning
      within the leaf is to investigate the endogenous variations of parameters related
      to carbon metabolism. This study of diurnal changes in the activities of sucrose
      synthesizing enzymes and levels of nonstructural carbohydrates in intact leaves
      of field-grown soybean plants (Glycine max [L.]) showed pronounced diurnal
      fluctuations in sucrose phosphate synthase (SPS) activity. However, there was no
      distinct diurnal change in the activity of fructose-1,6-bisphosphatase
      (F1,6BPase). SPS activity in leaves from plants grown in controlled environments
      presented two peaks during the light period. In contrast to field-grown plants,
      F1,6BPase activity in leaves from growth chamber-grown plants manifested one peak
      during the first half of the light period. In plants grown under both conditions,
      sucrose and starch accumulation rates were highest during early hours of the
      light period. By the end of the dark period, most of the starch was depleted. A
      pattern of diurnal fluctuations of abscisic acid (ABA) levels in leaves was also
      observed under all growing conditions. Either imposition of water stress or
      exogenous applications of ABA inhibited F1,6BPase activity. However, SPS
      extractable activity increased following water deficit but did not change in
      response to ABA treatment. Gibberellin application to intact soybean leaves
      increased levels of both starch and sucrose. Both gibberellic acid (10(-6)m) and
      gibberellins 4 and 7 (10(-5)m) increased the activity of SPS but had an
      inconsistent effect on F1,6BPase. Correlation studies between the activities of
      SPS and F1,6BPase suggest that these two enzymes are coordinated in their
      function, but the factors that regulate them may be distinct because they respond
      differently to certain environmental and physiological changes.

PMID- 16653111
TI  - Regulation of sucrose phosphate synthase by gibberellins in soybean and spinach
      plants.
AB  - Exogenous applications of gibberellins (GAs) increased the extractable activity
      of leaf sucrose phosphate synthase (SPS) in soybean (Glycine max [L.]) and
      spinach (Spinacia oleracea [L.]). The response to GA applications was detectable
      within 2 h postapplication and was still observed 6 h, 24 h, and 7 d after
      treatment. When paclobutrazol, a GA biosynthesis inhibitor, was applied to intact
      soybean and spinach plants, decreased extractable SPS activity resulted within 24
      h following the treatment. Different methods of GA application (spray, injection,
      capillary wick, and excised leaf systems) produced similar effects on SPS
      activity of soybean leaves. Protein synthesis in soybean leaves appeared to be
      necessary for GA-promoted SPS activity because gibberellic acid only partially
      reversed the inhibitory effect of pretreatment with cycloheximide. Levels of SPS
      protein from crude extracts of spinach plants were measured by a dot blot
      technique using monoclonal antibodies against SPS. Application of gibberellic
      acid to spinach leaves increased levels of SPS protein 2 h, 24 h, and 7 d after
      treatment. The results suggest that, in both soybean and spinach, GA is one of
      the endogenous hormonal factors that regulate the steady-state level of SPS
      protein and, hence, its activity.

PMID- 16653112
TI  - Involvement of Abscisic Acid in Regulating Water Status in Phaseolus vulgaris L.
      during Chilling.
AB  - During the first hours of chilling, bean (Phaseolus vulgaris L., cv Mondragone)
      seedlings suffer severe water stress and wilt without any significant increase in
      leaf abscisic acid (ABA) content (P. Vernieri, A. Pardossi, F. Tognoni [1991]
      Aust J Plant Physiol 18: 25-35). Plants regain turgor after 30 to 40 h. We
      hypothesized that inability to rapidly synthesize ABA at low temperatures
      contributes to chilling-induced water stress and that turgor recovery after 30 to
      40 h is mediated by changes in endogenous ABA content. Entire bean seedlings were
      subjected to long-term (up to 6 d) chilling (3 degrees C, 0.2-0.4 kPa vapor
      pressure deficit, 100 mumol.m(-2).s(-1) photosynthetic photon flux density,
      continuous fluorescent light). During the first 24 h, stomata remained open, and
      plants rapidly wilted as leaf transpiration exceeded root water absorption.
      During this phase, ABA did not accumulate in leaves or in roots. After 24 h, ABA
      content increased in both tissues, leaf diffusion resistance increased, and
      plants rehydrated and regained turgor. No osmotic adjustment was associated with
      turgor recovery. Following turgor recovery, stomata remained closed, and ABA
      levels in both roots and leaves were elevated compared with controls. The
      application of ABA (0.1 mm) to the root system of the plants throughout exposure
      to 3 degrees C prevented the chilling-induced water stress. Excised leaves fed
      0.1 mm ABA via the transpiration stream had greater leaf diffusion resistance at
      20 and 3 degrees C compared with non-ABA fed controls, but the amount of ABA
      needed to elicit a given degree of stomatal closure was higher at 3 degrees C
      compared with 20 degrees C. These findings suggest that endogenous ABA may play a
      role in ameliorating plant water status during chilling.

PMID- 16653113
TI  - Localization of Nitrate Absorption and Translocation within Morphological Regions
      of the Corn Root.
AB  - The absorption of NO(3) (-) was characterized in six regions of a 7-d-old corn
      root (Zea mays L. cv W64A x W182E) growing in a complete nutrient solution. Based
      on changing rates of (15)N accumulation during 15-min time courses, translocation
      of the concurrently absorbed N through each region of the intact root was
      calculated and distinguished from direct absorption from the medium. Of the (15)N
      accumulated in the 5-mm root tip after 15 min, less than 15 and 35% had been
      absorbed directly from the external solution at 0.1 and 10 mm NO(3) (-)
      concentration of the external solution, respectively. The characterization of the
      apical portion of the primary root as a sink for concurrently absorbed N was
      conconfirmed in a pulse-chase experiment that showed an 81% increase of (15)N in
      the 5-mm root tip during a 12-min chase (subsequent to a 6-min labeling period).
      The lateral roots alone accounted for 60% of root influx and 70% of 15-min whole
      root (15)N accumulation at either 0.1 or 10 mm. NO(3) (-) concentration of the
      external solution. Because relatively steady rates of (15)N accumulation in the
      shoot were reached after 6 min, the rapidly exchanging pools in lateral roots
      must have been involved in supplying (15)N to the shoot. The laterals and the
      basal primary root also showed large decreases (24 and 17%) in (15)N during the
      chase experiment, confirming their role in rapid translocation.

PMID- 16653114
TI  - Modulation of the Access of Exogenous NAD(P)H to the Alternative Pathway in
      Potato Tuber Callus Mitochondria with Triton X-100.
AB  - Alternative oxidase activity in potato tuber (Solanum tuberosum L. cv Bintje)
      callus mitochondria with exogenous NAD(P)H as substrate is inhibited by low
      concentrations of the detergent Triton X-100. Alternative oxidase activity with
      succinate or malate as substrate is not affected by these low concentrations of
      Triton X-100. Cytochrome pathway activity was not influenced under these
      conditions, neither with endogenous nor with exogenous substrate. Washing of
      Triton X-100-treated mitochondria did partially restore both uninhibited and CN
      resistant NADH oxidation, indicating that under these conditions Triton X-100
      does not permanently remove major components from the mitochondrial membrane.
      Apparently, it is possible to manipulate mitochondria in such a way that the
      access of exogenous NADH to the alternative pathway is blocked while access to
      the cytochrome pathway is uninhibited. It is suggested that membrane conditions
      have a regulatory function (possibly via influencing the diffusion path) in the
      oxidation of exogenous NADH via the alternative pathway.

PMID- 16653115
TI  - Oxygen radical generation by isolated microsomes from soybean seedlings.
AB  - The generation of active oxygen species by microsomes isolated from soybean
      seedlings was studied. NADPH-dependent superoxide anion production was 5.0 +/-
      0.4 nmol . min(-1) mg(-1) of microsomal protein. Hydrogen peroxide generation by
      microsomes was 1.40 +/- 0.05 nmol . min(-1) mg(-1) of protein. Hydroxyl radical
      production, in the presence of ferric EDTA, evaluated through the generation of
      formaldehyde from dimethyl sulfoxide or tert-butyl alcohol was 0.50 +/- 0.04 and
      0.44 +/- 0.03 nmol . min(-1) mg(-1), respectively. NADH proved to be suitable as
      cofactor for oxygen radical generation by microsomes from soybean seedlings.
      Because transition metals are implicated in radical generation by biological
      systems, the ability of microsomal membranes to reduce iron complexes was
      studied. Ferric ATP, ferric citrate, ferric ADP, ferric diethylenetriamine
      pentaacetic acid, and ferric EDTA were efficiently reduced in the presence of
      either NADPH or NADH as cofactor. The pattern of effectiveness of the different
      ferric complexes, on superoxide anion, hydrogen peroxide, and hydroxyl radical
      production, was similar to that found with animal microsomes. The data presented
      here indicate that microsomal ability to catalyze oxygen radical generation must
      be considered as an important contribution to cellular radical steady-state
      concentrations in cells from soybean seedlings.

PMID- 16653116
TI  - De Novo Synthesis of Plasma Membrane and Tonoplast Polypeptides of Barley Roots
      during Short-Term K Deprivation : In Search of the High-Affinity K Transport
      System.
AB  - [(35)S]Methionine labeling of intact barley roots (Hordeum vulgare cv Klondike)
      after short (6-12 h) and longer (18-24 and 90-96 h) periods of K(+) deprivation
      revealed that several membrane polypeptides were synthesized in significantly
      increased amounts following withdrawal of K(+) from nutrient solutions. One of
      these, a 43-kD polypeptide localized in plasma membrane- and tonoplast-enriched
      fractions, accounted for a large part of (35)S incorporation into membranes when
      [(35)S]methionine was administered for 6 h following 6 h of K(+) deprivation.
      With increasing duration of K(+) deprivation, (35)S incorporation into this 43-kD
      polypeptide decreased. This polypeptide, referred to as KR43, was not synthesized
      when NO(3) (-) or inorganic phosphate was removed or when Rb(+) was substituted
      for K(+). However, it was synthesized when K(+) was removed and replaced by an
      equivalent concentration of Na(+). The intrinsic nature of this polypeptide and
      the time course of changes in its expression, which correspond with changes of
      K(+)((86)Rb) influx associated with K(+) deprivation, provide evidence that this
      polypeptide may form part of the high-affinity K(+) transport system in barley
      roots. A possible role for this polypeptide is discussed in the context of
      changes in the subcellular distribution of K(+) in barley roots following
      interruption of K(+) supply. A 45-kD microsomal polypeptide, identified in
      earlier studies as a response to K(+) deprivation, is suggested to be an
      extrinsic protein, readily displaced from membranes by exposure to
      ethylenediaminetetraacetate.

PMID- 16653117
TI  - Enhancement of Naphthaleneacetic Acid-Induced Rhizogenesis in T(L)-DNA
      Transformed Brassica napus without Significant Modification of Auxin Levels and
      Auxin Sensitivity.
AB  - Determination of the abscisic acid and indoleacetic acid (IAA) contents of floral
      stem segments of nontransformed and pRi A(4) T(L)-DNA-transformed rape (Brassica
      napus L. var oleifera, cv Brutor) using a high performance liquid chromatography
      enzyme-linked immunosorbent assay procedure and mass spectrometry controls showed
      that IAA levels were not modified. The regeneration abilities of the in vitro
      cultured explants were compared on media supplemented with several plant growth
      regulator combinations. No regeneration occurred on hormone-free media, and shoot
      production was similar in both genotypes when supplemented with benzyladenine. In
      the presence of naphthaleneacetic acid (NAA), transformed explants were
      characterized by faster root regeneration and reduced shoot organogenesis. The
      optimum for root formation was the same in nontransformed and transformed plants,
      but the sensitivity threshold was slightly lower in the latter. The NAA inductive
      period was shorter (14 versus 22 h) with transformed tissue. Root neoformation
      occurred about 72 h earlier on transformed explants. Our results suggest mainly
      that there is an acceleration of the auxinic signal transduction and/or that the
      events preliminary to the formation of roots occur faster in the transformed
      tissues than in the normal ones.

PMID- 16653118
TI  - Effect of cold hardening on sensitivity of winter and spring wheat leaves to
      short-term photoinhibition and recovery of photosynthesis.
AB  - Photoinhibition of photosynthesis and its recovery were studied in wheat
      (Triticum aestivum L.) leaves grown at nonhardening (20 degrees C) and cold
      hardening (5 degrees C) temperatures. Cold-hardened wheat leaves were less
      susceptible to photoinhibition at 5 degrees C than nonhardened leaves, and the
      winter cultivars, Kharkov and Monopol, were less susceptible than the spring
      cultivar, Glenlea. The presence of chloramphenicol, a chloroplastic protein
      synthesis inhibitor, increased the susceptibility to photoinhibition, but cold
      hardened leaves still remained less susceptible to photoinhibition than
      nonhardened leaves. Recovery at 50 mumol m(-2) s(-1) photosynthetic photon flux
      density and 20 degrees C was at least biphasic, with a fast and a slow phase in
      all cultivars. Cold-hardened leaves recovered maximum fluorescence and maximum
      variable fluorescence in the dark-adapted state during the fast phase at a rate
      of 42% h(-1) compared with 22% h(-1) for nonhardened leaves. The slow phase
      occurred at similar rates (2% h(-1)) in cold-hardened and nonhardened leaves.
      Full recovery required up to 30 h. Fast-recovery phase was not reduced by either
      lowering the recovery temperature to 5 degrees C or by the presence of
      chloramphenicol. Slow-recovery phase was inhibited by both treatments. Hence, the
      fast phase of recovery does not require de novo chloroplast protein synthesis. In
      addition, only approximately 60% of the photochemical efficiency lost through
      photoinhibition at 5 degrees C was associated with lost [(14)C]atrazine binding
      and, hence, with damage to the secondary quinone electron acceptor for
      photosystem II-binding site. We conclude that the decrease in susceptibility to
      photoinhibition exhibited following cold hardening of winter and spring cultivars
      is not due to an increased capacity for repair of photoinhibitory damage at 5
      degrees C but reflects intrinsic properties of the cold-hardened photosynthetic
      apparatus. A model to account for the fast component of recovery is discussed.

PMID- 16653119
TI  - Monovinyl and divinyl protochlorophyllide pools in etiolated tissues of higher
      plants.
AB  - The composition of chlorophyll-precursor pigments, particularly the contents of
      monovinyl (MV) and divinyl (DV) protochlorophyllides (Pchlides), in etiolated
      tissues of higher plants were determined by polyethylene-column HPLC (Y. Shioi,
      S. I. Beale [1987] Anal Biochem 162: 493-499), which enables the complete
      separation of these pigments. DV-Pchlide was ubiquitous in etiolated tissue of
      higher plants. From the analyses of 24 plant species belonging to 17 different
      families, it was shown that the concentration of DV-Pchlide was strongly
      dependent on the plant species and the age of the plants. The ratio of DV-Pchlide
      to MV-Pchlide in high DV-Pchlide plants such as cucumber and leaf mustard
      decreased sharply with increasing age. Levels of DV-Pchlide in Gramineae plants
      were considerably lower at all ages compared with those of other plants.
      Etiolated tissues of higher plants such as barley and corn were, therefore, good
      sources of MV-Pchlide. Absorption spectra of the purified MV- and DV-Pchlides in
      ether are presented and compared.

PMID- 16653120
TI  - Polyphosphoinositide Phospholipase C in Plasma Membranes of Wheat (Triticum
      aestivum L.) : Orientation of Active Site and Activation by Ca and Mg.
AB  - Polyphosphoinositide-specific phospholipase C activity was present in plasma
      membranes isolated from different tissues of several higher plants. Phospholipase
      C activities against added phosphatidylinositol 4-phosphate (PIP) and
      phosphatidylinositol 4,5-bisphosphate (PIP(2)) were further characterized in
      plasma membrane fractions isolated from shoots and roots of dark-grown wheat
      (Triticum aestivum L. cv Drabant) seedlings. In right-side-out (70-80% apoplastic
      side out) plasma membrane vesicles, the activities were increased 3 to 5 times
      upon addition of 0.01 to 0.025% (w/v) sodium deoxycholate, whereas in fractions
      enriched in inside-out (70-80% cytoplasmic side out) vesicles, the activities
      were only slightly increased by detergent. Furthermore, the activities of inside
      out vesicles in the absence of detergent were very close to those of right-side
      out vesicles in the presence of optimal detergent concentration. This verifies
      the general assumption that polyphosphoinositide phospholipase C activity is
      located at the cytoplasmic surface of the plasma membrane. PIP and PIP(2)
      phospholipase C was dependent on Ca(2+) with maximum activity at 10 to 100 mum
      free Ca(2+) and half-maximal activation at 0.1 to 1 mum free Ca(2+). In the
      presence of 10 mum Ca(2+), 1 to 2 mm MgCl(2) or MgSO(4) further stimulated the
      enzyme activity. The other divalent chloride salts tested (1.5 mm Ba(2+), Co(2+),
      Cu(2+), Mn(2+), Ni(2+), and Zn(2+)) inhibited the enzyme activity. The
      stimulatory effect by Mg(2+) was observed also when 35 mm NaCl was included.
      Thus, the PIP and PIP(2) phospholipase C exhibited maximum in vitro activity at
      physiologically relevant ion concentrations. The plant plasma membrane also
      possessed a phospholipase C activity against phosphatidylinositol that was 40
      times lower than that observed with PIP or PIP(2) as substrate. The
      phosphatidylinositol phospholipase C activity was dependent on Ca(2+), with
      maximum activity at 1 mm CaCl(2), and could not be further stimulated by Mg(2+).

PMID- 16653121
TI  - Water relation parameters of embryogenic cultures and seedlings of larch.
AB  - Changes in the water relations parameters of developing somatic embryogenic and
      xygotic European larch (Larix decidua) were studied. Water release curves were
      generated by suspending tissue samples over unsaturated NaCl solutions until they
      reached vapor equilibration with the surrounding air. Twenty solutions were used
      whose water potentials ranged from -0.05 to -10 MPa. Water release curves were
      obtained by plotting paired values of tissue relative water content (RWC) and
      solution potential. Curves were derived for embryonic larch at various stages of
      development and for hypocotyls and roots from germinated zygotic and somatic
      embryos. The ability to resist dehydration increased markedly with development.
      Stage 1 tissue, which consisted of clusters of loosely associated
      nonchlorophyllous cells, had extremely low bulk elastic modulus (epsilon) (1.91
      MPa) and apoplastic water content (A) (0.023), relatively high osmotic potential
      (Psi(pi)) (-0.53 MPa), and lost turgor at 0.56 RWC. In contrast, mature embryoids
      with primary roots, hypocotyl, and cotyledons (stage 3) had an almost 4-fold
      increase in A (0.089), significantly higher epsilon (3.49 MPa), and lower Psi(pi)
      (-0.88 MPa) and lost turgor at 0.66 RWC. Hypocotyl tissue from germinated somatic
      embryos lost turgor at 0.74 RWC and had higher epsilon, A, and solute
      accumulation than pregerminated tissue. Hypocotyl tissue resisted dehydration
      more strongly than root tissue, and differences between root and hypocotyl water
      relation parameters were more pronounced in xygotic than in somatic seedlings.
      Highest dehydration resistance was in zygotic hypocotyls. The characterization of
      the water relations of tissue cultures should allow the development of more
      consistent and reliable desiccation protocols to induce maturation of embryos and
      produce synchronously germinating seed.

PMID- 16653122
TI  - Slow degradation of the d1 protein is related to the susceptibility of low-light
      grown pumpkin plants to photoinhibition.
AB  - Photoinhibition of photosystem II (PSII) electron transport and subsequent
      degradation of the D1 protein were studied in pumpkin (Cucurbita pepo L.) leaves
      developed under high (1000 mumol m(-2) s(-1)) and low (80 mumol m(-2) s(-1))
      photon flux densities. The low-light leaves were more susceptible to high light.
      This difference was greatly diminished when illumination was performed in the
      presence of chloramphenicol, indicating that a poor capacity to repair
      photodamaged PSII centers is decisive in the susceptibility of low-light leaves
      to photoinhibition. In fact, the first phases of the repair cycle, degradation
      and removal of photodamaged D1 protein from the reaction center complex, occurred
      slowly in low-light leaves, whereas in high-light leaves the degradation of the
      D1 protein more readily followed photoinhibition of PSII electron transport. A
      modified form of the D1 protein, with slightly slower electrophoretic mobility
      than the original D1, accumulated in the appressed thylakoid membranes of low
      light leaves during illumination and was subsequently degraded only slowly.

PMID- 16653123
TI  - The Role of beta-Galactosidases in the Modification of Cell Wall Components
      during Muskmelon Fruit Ripening.
AB  - The changes in activities of soluble beta-galactosidase and two forms of wall
      bound beta-galactosidases extracted with NaCl and EDTA were investigated
      throughout the development of muskmelon (Cucumis melo L. cv Prince) fruits. DEAE
      cellulose ion-exchange chromatography of soluble beta-galactosidase revealed the
      presence of two isoforms. Soluble isoform I was detected in all stages throughout
      the fruit development, whereas soluble isoform II appeared around 34 d after
      anthesis when fruit ripening initiated. Both NaCl- and EDTA-released beta
      galactosidase activities also increased as ripening proceeded. The soluble and
      wall-bound forms behaved differently upon ion-exchange chromatography.
      Enzymological properties such as optimum pH, optimum temperature, K(m) values for
      p-nitrophenyl beta-d-galactopyranoside, and inhibition by metal ions were nearly
      similar in all forms. Molecular sizes of pectic polymers and hemicelluloses
      extracted from fruit mesocarp cell walls were shifted from larger to smaller
      polymers during ripening, as determined by gel filtration profiles. NaCl-released
      beta-galactosidase from cell walls of ripe fruits had the ability to degrade in
      vitro the pectin extracted from preripe fruit cell walls to smaller sizes of
      pectin similar to those that were observed in ripe cell walls in situ. Both
      soluble isoform I and II were able to degrade in vitro the 5% KOH-extractable
      hemicellulose from preripe fruit cell walls to sizes of molecules similar to
      those that were observed in ripe cell walls in situ. Soluble isoform I and the
      NaCl-released form from ripe fruits were able to modify in vitro 24% KOH
      extractable hemicellulose from preripe cell walls to sizes of molecules similar
      to those that were observed in ripe fruits in situ.

PMID- 16653124
TI  - Pleiotropic Effects of sym-17 : A Mutation in Pisum sativum L. cv Sparkle Causes
      Decreased Nodulation, Altered Root and Shoot Growth, and Increased Ethylene
      Production.
AB  - R82 (sym-17), a stable mutant of Pisum sativum L. cv Sparkle, is described. The
      shoot growth of the mutant was less than that of its parent under light or dark
      growth conditions. Gibberellic acid treatment did not normalize the shoot growth
      of R82. The mutant had thick and short roots. It formed few nodules, but the
      specific nitrogenase activity was not affected. R82 produced and contained more
      ethylene than Sparkle. It also contained more free 1-amino-cyclopropane-1
      carboxylic acid than did its parent in both the shoot and the root. The root tip
      of R82 had a lower activity of ethylene-forming enzyme than that of Sparkle,
      whereas the whole shoot of R82 had a similar activity. The sensitivity of R82 to
      exogenous ethylene was not more than that of Sparkle. Exogenous ethylene
      treatments did not make Sparkle mimic R82, and inhibitors of ethylene
      biosynthesis or action did not normalize the phenotype of R82. The data suggest
      that the primary effect of sym-17 is not the enhanced ethylene production.

PMID- 16653125
TI  - Ethylene as a Possible Mediator of Light- and Nitrate-Induced Inhibition of
      Nodulation of Pisum sativum L. cv Sparkle.
AB  - Exposure of pea (Pisum sativum L. cv Sparkle) roots to light suppressed
      nodulation and induced an increase in ethylene production by roots. Dim light did
      not affect the number of infections per centimeter of root on the primary root,
      but most infections were blocked when the infection thread was in the epidermis
      or in the outer cortex. This is the same stage of infection on lateral roots that
      is blocked by exogenous ethylene. Silver, an inhibitor of ethylene action,
      increased nodule number on roots exposed to dim light. Exposure of pea roots to
      nitrate also suppressed nodulation and induced increased ethylene production by
      roots. However, induction of ethylene production from roots by nitrate was less
      than that induced by dim light. Nitrate decreased the number of infections per
      centimeter of lateral root. With 25 mm nitrate, about half of the infections that
      occurred were blocked in the epidermis or in the outer cortex. Silver did not
      reverse the inhibitory effects of nitrate on nodulation. Our data indicate that
      the inhibitory effect of light may occur via increased ethylene production, but
      they do not support the hypothesis that ethylene mediates nitrate control of
      nodule number. The possible role of ethylene in regulating nodule number should
      be studied in experiments in which light is excluded from the roots.

PMID- 16653126
TI  - Specific and abundant secretion of a novel hydroxyproline-rich glycoprotein from
      salt-adapted winged bean cells.
AB  - Winged bean callus was adapted to increasing concentrations of NaCl by sequential
      transfer to medium with 0, 0.5, 1.0, 1.5, and 2.0% (w/v) NaCl. When the culture
      media, after cell suspension cultures of callus adapted to 0.5 (SA-0.5), 1.0 (SA
      1.0), 1.5 (SA-1.5), or 2.0% (w/v) NaCl (SA-2.0), were analyzed by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis, six specific or enhanced
      polypeptide bands (SAP1, -2, -3, -4, -5, and -6) were observed. SAP1, with a
      molecular weight of 84,000, was abundantly secreted in suspension cultures of SA
      1.0 and SA-1.5, and was observed as the most striking polypeptide band. The SAP1
      yield was about 4 mg/g cells fresh weight. SAP1 was abundantly secreted after the
      suspension culture of SA-1.0 in the presence of AlCl(3), but little was secreted
      in the presence of KCl, LiCl, CaCl(2), MgCl(2), mannitol, sucrose, or abscisic
      acid. SAP1 was purified from the culture medium after suspension culture of SA
      1.0 in the presence of 1.0% (w/v) NaCl. Two steps, ammonium sulfate fractionation
      and CM-cellulose chromatography, were sufficient for purification to homogeneity.
      Finally, about 5 mg of SAP1 could be isolated from 7 g of fresh callus cells. Of
      the amino-terminal 32 amino acid residues of SAP1, 10 and 5 were found to be
      hydroxyproline and proline, respectively. SAP1 on an acrylamide gel was stained
      by the periodic acid-Schiff method. It is interesting that SAP1 has
      pentahydroxyproline blocks (Hyp(5)) instead of tetrahydroxyproline blocks
      (Hyp(4)) common to many hydroxyproline-rich glycoproteins in dicotyledons. Thus,
      this novel hydroxyproline-rich glycoprotein was shown to be abundantly secreted
      from NaCl-adapted winged bean cells.

PMID- 16653127
TI  - Regulation of indole-3-acetic Acid biosynthetic pathways in carrot cell cultures.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) promotes the accumulation of tryptophan
      derived indole-3-acetic acid (IAA) in carrot cell cultures during callus
      proliferation by a biosynthetic pathway that is apparently not active during
      somatic embryo formation. The effects of 2,4-D were examined by measuring the
      isotopic enrichment of IAA due to the incorporation of stable isotope-labeled
      precursors (deuterium oxide, [(15)N]indole, and (2)H(5)-l-tryptophan). Enrichment
      of IAA from deuterium oxide is similar in both cultured hypocotyls and cell
      suspension cultures in the presence and absence of 2,4-D, despite the large
      differences in absolute IAA concentrations. The enrichment of IAA due to the
      incorporation of [(15)N]indole is also similar in callus proliferating in the
      presence of 2,4-D and in embryos developing in the absence of 2,4-D. The
      incorporation of (2)H(5)-l-tryptophan into IAA, however, is at least 7-fold
      higher in carrot callus cultures proliferating in the presence of 2,4-D than in
      embryos developing in the absence of 2,4-D. Other experiments demonstrated that
      this differential incorporation of (2)H(5)-l-tryptophan into IAA does not result
      from differential tryptophan uptake or its subsequent compartmentation. Thus, it
      appears that differential pathways for IAA synthesis operate in callus cultures
      and in developing embryos, which may suggest that a relationship exists between
      the route of IAA biosynthesis and development.

PMID- 16653128
TI  - Gibberellin concentration and transport in genetic lines of pea : effects of
      grafting.
AB  - Effects of the Na and Le loci on gibberellin (GA) content and transport in pea
      (Pisum sativum L.) shoots were studied. GA(1), GA(8), GA(17), GA(19), GA(20),
      GA(29), GA(44), GA(8) catabolite, and GA(29) catabolite were identified by full
      scan gas chromatography-mass spectrometry in extracts of expanding and fully
      expanded tissues of line C79-338 (Na Le). Quantification of GAs by gas
      chromatography-single-ion monitoring using deuterated internal standards in lines
      differing at the Na and Le alleles showed that na reduced the contents of GA(19),
      GA(20), and GA(29) on average to <3% and of GA(1) and GA(8) to <30% of those in
      corresponding Na lines. In expanding tissues from Na le lines, GA(1) and GA(8)
      concentrations were reduced to approximately 10 and 2%, respectively, and GA(29)
      content increased 2- to 3-fold compared with those in Na Le plants. There was a
      close correlation between stem length and the concentrations of GA(1) or GA(8) in
      shoot apices in all six genotypes investigated. In na/Na grafts, internode length
      and GA(1) concentration of nana scions were normalized, the GA(20) content
      increased slightly, but GA(19) levels were unaffected. Movement of labeled GAs
      applied to leaves on Na rootstocks indicated that GA(19) was transported poorly
      to apices of na scions compared with GA(20) and GA(1). Our evidence suggests that
      GA(20) is the major transported GA in peas.

PMID- 16653129
TI  - Coupling of Carbon Dioxide Fixation to the Oxyhydrogen Reaction in the Isolated
      Chloroplast of Chlamydomonas reinhardtii.
AB  - The oxyhydrogen reaction (the reduction of O(2) to water by H(2)) in the presence
      of CO(2) was studied in the isolated Chlamydomonas reinhardtii chloroplast by
      monitoring the rate of (14)CO(2) incorporation into acid-stable products in the
      dark. The endogenous rate of CO(2) uptake (50-125 nmol/mg chlorophyll per h) was
      increased about 3- to 4-fold by ATP and additionally when combined with glucose,
      ribose-5-phosphate, and glycerate-3-phosphate. The rate was diminished 50 to 75%,
      respectively, when H(2) was replaced by N(2) or by air. Decrease in CO(2) uptake
      by dl-glyceraldehyde was taken to indicate that the regenerative phase and
      complete Calvin cycle turnover were involved. Diminution of CO(2) incorporation
      by rotenone, antimycin A, and 2,5-dibromo-3-methyl-6-isopropanol-p-benzoquinone
      was attributed to an inhibition of the oxyhydrogen reaction, resulting in an
      elevated NADPH/NADP ratio. If so, then the diminished CO(2) uptake could have
      been by "product inhibition" of the carbon metabolic network. Our data are
      consistent with the proposal (H. Gaffron [1942] J Gen Physiol 26: 241-267) that
      CO(2) fixation coupled to the oxyhydrogen reaction is dependent to some extent on
      exchloroplastic metabolism. This support is primarily ATP provided by
      mitochondrial respiration.

PMID- 16653130
TI  - Inactivation of maize phosphoenolpyruvate carboxylase by urea.
AB  - Phosphoenolpyruvate carboxylase purified from leaves of maize (Zea mays, L.) is
      sensitive to the presence of urea. Exposure to 2.5 m urea for 30 min completely
      inactivates the enzyme, whereas for a concentration of 1.5 m urea, about 1 h is
      required. Malate appears to have no effect on inactivation by urea of
      phosphoenolpyruvate carboxylase. However, the presence of 20 mm
      phosphoenolpyruvate or 20 mm glucose-6-phosphate prevents significant
      inactivation by 1.5 m urea for at least 1 h. The inactivation by urea is
      reversible by dilution. The inhibition by urea and the protective effects of
      phosphoenolpyruvate and glucose-6-phosphate are associated with changes in
      aggregation state.

PMID- 16653131
TI  - Inhibition of phytoalexin biosynthesis in elicitor-treated tobacco cell
      suspension cultures by calcium/calmodulin antagonists.
AB  - A role for calcium/calcium-binding proteins in a mechanism of signaling elicitor
      inducible phytoalexin biosynthesis was investigated. Two classes of
      calcium/calmodulin antagonists, phenothiazines and naphthalenesulfonamides,
      inhibited sesquiterpene phytoalexin accumulation in tobacco (Nicotiana tabacum)
      cell-suspension cultures when added 1 h before elicitor. The antagonists also
      inhibited the induction of sesquiterpene cyclase enzyme activity, a key
      regulatory enzyme for sesquiterpene biosynthesis. The antagonists suppressed the
      induction of sesquiterpene cyclase only if added before or simultaneously with
      elicitor. Additionally, the antagonists inhibited (a) accumulation of the cyclase
      protein as measured in immunoblots; (b) the in vivo synthesis rate of the cyclase
      protein, measured as the incorporation of [(35)S]methionine into
      immunoprecipitable cyclase protein; and (c) the cyclase mRNA translational
      activity, measured as the incorporation of [(35)S]methionine into
      immunoprecipitable cyclase protein synthesized by in vitro translation of RNA
      isolated from antagonist-treated, elicitor-induced cells. In contrast, elicitor
      inducible phenylalanine ammonia lyase enzyme activity, the level of the enzyme
      protein, the in vivo synthesis rate, and the mRNA translational activity were not
      affected by any of the antagonist treatments. Uptake and incorporation of
      [(35)S]methionine into total cellular proteins and total in vitro translation
      products were also not indiscriminately altered by the antagonist treatments. The
      current results suggest that calcium and/or calmodulin-like proteins may be
      elements of a signal transduction pathway mediating elicitor-induced accumulation
      of phytoalexins in tobacco.

PMID- 16653132
TI  - Effect of brassinolide on gene expression in elongating soybean epicotyls.
AB  - We have studied the effect of brassinolide (BR), a plant steroidal lactone, on
      the expression of auxin-regulated genes in soybean (Glycine max L. cv Williams
      82) epicotyls. BR caused up to 4-fold increases in epicotyl length during
      extended assays at 10(-7)m, in the absence of added auxin. Structurally related
      steroids failed to induce elongation or to alter the BR effect. Northern blot
      analysis, using sequences corresponding to auxin-regulated genes as probes, has
      shown that the molecular mechanism of BR-induced elongation is likely to differ
      from that of auxin-induced elongation in this system. BR does not rapidly induce
      members of the GH, SAUR, or JCW auxin-inducible gene families before the onset of
      elongation. BR enhances SAUR and GH1 transcripts after 18 h but has no effect on
      JCW1 or GH3 transcripts at any time examined. We have shown by two-dimensional
      gel analysis of in vitro translated mRNA that a submicromolar concentration of BR
      alters the pattern of gene expression in elongating soybean epicotyls.

PMID- 16653133
TI  - Coordinate Gene Response to Salt Stress in Lophopyrum elongatum.
AB  - Lophopyrum elongatum is a highly salt-tolerant relative of wheat. A previous
      study showed that the abundance of a number of mRNA species is enhanced or
      reduced in the roots of the L. elongatum x Triticum aestivum amphiploid by salt
      stress. Eleven genes with enhanced expression in the roots of salt-stressed L.
      elongatum plants have been cloned as cDNAs. The clones were used as probes to
      characterize temporal expression of these genes in roots after initiation of salt
      (250 mm NaCl) stress. All 11 genes are induced within 2 h after exposure to 250
      mm NaCl and reached peak expression after 6 h. The decline of gene expression
      distinguished two groups, one in which mRNA concentrations returned to basal
      levels by 24 h and the other in which this occurred between 3 and 7 d. One of the
      11 clones was found to be homologous to a multigene family of abscisic acid
      induced genes, rab and dhn, identified in other species. We suggest that the
      coordinate expression of this large number of genes reflects the existence of a
      highly specific early response to salt stress. We refer to this response as the
      "early salt stress response."

PMID- 16653134
TI  - Endogenous rhythmicity of ethylene production in growing intact cereal seedlings.
AB  - Ethylene evolution from etiolated barley (Hordeum vulgare), wheat (Triticum
      aestivum), and rye (Secale cereale) seedlings during coleoptile growth followed a
      rhythmic pattern, with a period of about 16 h for barley and wheat and 12 h for
      rye seedlings. Leaf emergence disturbed the established rhythm of ethylene
      evolution.

PMID- 16653135
TI  - Ubiquitin Conjugation to Protein Increases following Chilling of Clerodendrum
      Leaves.
AB  - The protein content of clerodendrum (Clerodendrum speciosum) leaves declines
      following chilling (48 h, 3 degrees C). Using western and dot blots and
      fluorescence immunoassays, we found that isolated leaf proteins had more
      conjugated ubiquitin following chilling. In contrast, the amount of free
      ubiquitin declined by almost 90% after chilling. The increase in ubiquitin
      conjugation was greater in the membrane fraction than in the soluble fraction.

PMID- 16653136
TI  - Metabolism of Auxin in Tomato Fruit Tissue: Formation of High Molecular Weight
      Conjugates of Oxindole-3-Acetic Acid via the Oxidation of Indole-3-Acetylaspartic
      Acid.
AB  - High performance liquid chromatography of extracts of tomato (Lycopersicon
      esculentum Mill.) incubated with a relatively low concentration (4 mum) of [1
      (14)C]indole-3-acetic acid (IAA) revealed the presence of two major polar
      metabolites. Hydrolysis of the two metabolites with 7 n NaOH yielded the same
      compound, which had a retention time similar to that of ring-expanded oxindole-3
      acetic acid (OxIAA) on high performance liquid chromatography. The identity of
      the indolic moiety of these conjugates as OxIAA was further confirmed by gas
      chromatography-mass spectrometry. Chromatography of the two OxIAA conjugates on a
      calibrated Bio-Gel P-2 column indicated that their molecular weights are about
      1200 and 1000. Aspartic acid and glutamic acid were the major amino acids
      detected in acid hydrolysates of the two conjugates. Increasing the concentration
      of IAA in the incubation medium resulted in an increase in the formation of
      indole-3-acetylaspartic acid (IAAsp) with a concomitant decrease in the formation
      of the two OxIAA conjugates. Feeding experiments with labeled IAAsp and OxIAA
      showed that IAAsp and not OxIAA is the precursor of these conjugates. The data
      obtained indicate that exogenous IAA is converted in tomato pericarp tissue to
      high molecular weight conjugates, presumably peptides, of OxIAA via the oxidation
      of IAAsp. The oxidation of IAAsp seems to be a rate-limiting step in the
      formation of these conjugates from exogenous IAA.

PMID- 16653137
TI  - Temperature and Photoperiod Influence Trichome Density and Sesquiterpene Content
      of Lycopersicon hirsutum f. hirsutum.
AB  - Resistance to Colorado potato beetle in a clone of Lycopersicon hirsutum f.
      hirsutum L. is attributed to the presence of the sesquiterpene zingiberene in the
      type VI leaf trichomes; however, both day/night temperature regimen and
      photoperiod affect zingiberene content and trichome density. In short days (SD),
      zingiberene content per trichome is more than 3-fold greater than in long days.
      In SD, trichome density per unit leaf surface is 2-fold greater at 25/20 degrees
      C (day/night) than at either 30/25 degrees C or 20/15 degrees C, thus indirectly
      influencing zingiberene content per cm(2). In long days, temperature regimen had
      little effect on either trichome density or zingiberene content, although
      trichome density was greater than or equal to that in SD.

PMID- 16653138
TI  - Production and Characterization of Monoclonal Antibodies against NADPH-Cytochrome
      P-450 Reductases from Helianthus tuberosus.
AB  - Monoclonal antibodies (mAbs) against a plant NADPH-cytochrome P-450 (Cyt P-450)
      reductase from Jerusalem artichoke (Helianthus tuberosus) tuber were prepared.
      These antibodies were produced by hybridoma resulting from the fusion of spleen
      cells from a rat immunized with a purified preparation of the reductase and mouse
      myeloma cells. The mAbs thus obtained were screened for their interaction with
      the reductases, first in western dots and then in blots, and for their ability to
      inhibit the NADPH-cytochrome c (Cyt c) reductase activity from Jerusalem
      artichoke microsomes. Among the 11 clones giving a positive response on western
      blots, only 6 were also able to inhibit microsomal NADPH-Cyt c reductase
      activity, and the microsomal Cyt P-450 monooxygenase activities dependent upon
      electrons transferred by the reductase. Thus, two families of mAbs were
      characterized: a family of mAbs that interact with epitopes of the reductase
      implicated in the reduction of Cyt P-450 by NADPH (binding sites for NADPH,
      flavin mononucleotide, flavin adenine dinucleotide, and Cyt P-450), and a
      structural family, whose members recognize epitopes outside the active site of
      the reductases. These mAbs specifically recognize the reductase, and all of them
      interact with all of the isoforms, indicating that important primary or secondary
      structural analogies exist between the isoforms, not only at the active site, but
      also at the level of epitopes not directly associated with catalytic activity.

PMID- 16653139
TI  - Metabolite activation of crassulacean Acid metabolism and c(4)
      phosphoenolpyruvate carboxylase.
AB  - The effects of glycine, alanine, serine, and various phosphorylated metabolites
      on the activity of phosphoenolpyruvate (PEP) carboxylase from Zea mays and
      Crassula argentea were studied. The maize enzyme was found to be activated by
      amino acids at a site that is separate from the glucose 6-phosphate binding site.
      The combination of glycine and glucose 6-phosphate synergistically reduced the
      apparent K(m) of the enzyme for PEP and increased the apparent V(max). Of the
      amino acids tested, glycine showed the lowest apparent K(a) and caused the
      greatest activation. d-Isomers of alanine and serine were more effective
      activators than the l-isomers. Unlike the maize enzyme, the Crassula enzyme was
      not activated by amino acids. Activation of either the Crassula or maize enzyme
      by glucose 6-phosphate occurred without dephosphorylation of the activator
      molecule. Furthermore, the Crassula enzyme was activated by two compounds
      containing phosphonate groups whose carbon-phosphorus bonds were not cleaved by
      the enzyme. A study of analogs of glucose 6-phosphate with Crassula PEP
      carboxylase revealed that the identity of the ring heteroatom was a significant
      structural feature affecting activation. Activation was not highly sensitive to
      the orientation of the hydroxyl group at the second or fourth carbon positions or
      to the presence of a hydroxyl group at the second position. However, the position
      of the phosphate group was found to be a significant factor.

PMID- 16653140
TI  - Ionic Current Changes Associated with the Gravity-Induced Bending Response in
      Roots of Zea mays L.
AB  - A vibrating probe was used to measure the changes in ionic currents around
      gravistimulated roots of Zea mays L. in an effort to determine whether these
      currents are involved in stimulus transduction from the root cap to the
      elongation zone. We did not observe a migration of the previously reported auxin
      insensitive current efflux associated with gravity sensing (T. Bjorkman, A.C.
      Leopold [1987] Plant Physiol 84:841-846) back from the root cap. Instead,
      beginning 10 to 15 min after gravistimulation, an asymmetry in current developed
      simultaneously along the root around the meristem and apical regions of the
      elongation zone. This asymmetry comprised a proton efflux from the upper surface,
      which was superimposed on the symmetrical pattern around the vertical root. The
      gravity-induced proton efflux was inhibited by the application of the auxin
      transport inhibitor, 2,3,5-triiodobenzoic acid, whereas the calcium channel
      blocker, lanthanum, had little effect. Because the onset of the gravity-induced
      current asymmetry coincided both spatially and temporally with the onset of the
      differential growth response, we suggest that this current efflux may result from
      auxin-requiring acid-growth phenomena in the upper root tissue. The implications
      of this simultaneous onset of both proton efflux and elongation for theories
      about gravity stimulus transduction are discussed.

PMID- 16653141
TI  - Tissue Distribution of Glutamate Synthase and Glutamine Synthetase in Rice Leaves
      : Occurrence of NADH-Dependent Glutamate Synthase Protein and Activity in the
      Unexpanded, Nongreen Leaf Blades.
AB  - To further explore the function of NADH-dependent glutamate synthase (GOGAT), the
      tissue distribution of NADH-GOGAT protein and activity was investigated in rice
      (Oryza sativa L.) leaves. The distributions of ferredoxin (Fd)-dependent GOGAT,
      plastidic glutamine synthetase, and cytosolic glutamine synthetase proteins were
      also determined in the same tissues. High levels of NADH-GOGAT protein (33.1 mug
      protein/g fresh weight) and activity were detected in the 10th leaf blade before
      emergence. The unexpanded, nongreen portion of the 9th leaf blade contained more
      than 50% of the NADH-GOGAT protein and activity per gram fresh weight when
      compared with the 10th leaf. The expanding, green portion of the 9th leaf blade
      outside of the sheath contained a slightly lower abundance of NADH-GOGAT protein
      than the nongreen portion of the 9th blade on a fresh weight basis. The fully
      expanded leaf blades at positions lower than the 9th leaf had decreased NADH
      GOGAT levels as a function of increasing age, and the oldest, 5th blade contained
      only 4% of the NADH-GOGAT protein compared with the youngest 10th leaf blade. Fd
      GOGAT protein, on the other hand, was the major form of GOGAT in the green
      tissues, and the highest amount of Fd-GOGAT protein (111 mug protein/g fresh
      weight) was detected in the 7th leaf blade. In the nongreen 10th leaf blade, the
      content of Fd-GOGAT protein was approximately 7% of that found in the 7th leaf
      blade. In addition, the content of NADH-GOGAT protein in the 10th leaf blade was
      about 4 times higher than that of Fd-GOGAT protein. The content of plastidic
      glutamine synthetase polypeptide was also the highest in the 7th leaf blade (429
      mug/g fresh weight) and lowest in nongreen blades and sheaths. On the other hand,
      the relative abundance of the cytosolic glutamine synthetase polypeptide was the
      highest in the oldest leaf blade, decreasing to 10 to 20% of that value in young,
      nongreen leaves. These results suggest that NADH-GOGAT is important for the
      synthesis of glutamate from the glutamine that is transported from senescing
      source tissues through the phloem in the nongreen sink tissues in rice leaves.

PMID- 16653142
TI  - Turnover of soluble proteins in the wheat sieve tube.
AB  - Although the enucleate conducting cells of the phloem are incapable of protein
      synthesis, phloem exudates characteristically contain low concentrations of
      soluble proteins. The role of these proteins and their movement into and out of
      the sieve tubes poses important questions for phloem physiology and for cell-to
      cell protein movement via plasmodesmata. The occurrence of protein turnover in
      sieve tubes was investigated by [(35)S]methionine labeling and by the use of
      aphid stylets to sample the sieve tube contents at three points along a source-to
      sink pathway (flag leaf to grains) in wheat plants (Triticum aestivum L.).
      Protein concentration and composition were similar at all sampling sites. The
      kinetics of (35)S-labeling of protein suggested a basically source-to-sink
      pattern of movement for many proteins. However, an appreciable amount of protein
      synthesis and, presumably, removal also occurred along the path. This movement
      appeared to be protein specific and not based on passive molecular sieving. The
      results have important implications for the transport capacities of plasmodesmata
      between sieve tubes and companion cells. The observations considerably expand the
      possible basis for ongoing sieve tube-companion cell interactions and, perhaps,
      interaction between sources and sinks.

PMID- 16653143
TI  - Photophysiology of the Elongated Internode (ein) Mutant of Brassica rapa: ein
      Mutant Lacks a Detectable Phytochrome B-Like Polypeptide.
AB  - Several phytochrome-controlled processes have been examined in etiolated and
      light-grown seedlings of a normal genotype and the elongated internode (ein/ein)
      mutant of rapid-cycling Brassica rapa. Although etiolated ein seedlings displayed
      normal sensitivity to prolonged far-red light with respect to inhibition of
      hypocotyl elongation, expansion of cotyledons, and synthesis of anthocyanin, they
      displayed reduced sensitivity to prolonged red light for all three of these
      deetiolation responses. In contrast to normal seedlings, light-grown ein
      seedlings did not show a growth promotion in response to end-of-day far-red
      irradiation. Additionally, whereas the first internode of light-grown normal
      seedlings showed a marked increase in elongation in response to reduced ratio of
      red to far-red light, ein seedlings showed only a small elongation response. When
      blots of protein extracts from etiolated and light-treated ein and normal
      seedlings were probed with monoclonal antibody to phytochrome A, an
      immunostaining band at about 120 kD was observed for both extracts. The
      immunostaining intensity of this band was substantially reduced for extracts of
      light-treated normal and ein seedlings. A mixture of three monoclonal antibodies
      directed against phytochrome B from Arabidopsis thaliana immunostained a band at
      about 120 kD for extracts of etiolated and light-treated normal seedlings. This
      band was undetectable in extracts of ein seedlings. We propose that ein is a
      photoreceptor mutant that is deficient in a light-stable phytochrome B-like
      species.

PMID- 16653144
TI  - Rapid stimulation of 5-lipoxygenase activity in potato by the fungal elicitor
      arachidonic Acid.
AB  - The activity of lipoxygenase (LOX) in aged potato tuber discs increased by almost
      2-fold following treatment of the discs with the fungal elicitor arachidonic acid
      (AA). Enzyme activity increased above that in untreated discs within 30 min after
      AA treatment, peaked at 1 to 3 h, and returned to near control levels by 6 h. The
      majority of the activity was detected in a soluble fraction (105,000g
      supernatant), but a minor portion was also associated with a particulate fraction
      enriched in microsomal membranes (105,000g pellet); both activities were
      similarly induced. 5-Hydroperoxyeicosatetraenoic acid was the principal product
      following incubation of these extracts with AA. Antibodies to soybean LOX
      strongly reacted with a protein with a molecular mass of approximately 95-kD
      present in both soluble and particulate fractions whose abundance generally
      corresponded with LOX activity in extracts. LOX activity was not enhanced by
      treatment of the discs with nonelicitor fatty acids or by branched beta-glucans
      from the mycelium of Phytophthora infestans. Prior treatment of the discs with
      abscisic acid, salicylhydroxamic acid, or n-propyl gallate, all of which have
      been shown to suppress AA induction of the hypersensitive response, inhibited the
      AA-induced increment in LOX activity. Cycloheximide pretreatment, which abolishes
      AA elicitor activity for other responses such as phytoalexin induction, did not
      inhibit LOX activity in water- or elicitor-treated discs but enhanced activity
      similar to that observed by AA treatment. The elicitor-induced increase in 5-LOX
      activity preceded or temporally paralleled the induction of other studied
      responses to AA, including the accumulation of mRNAs for 3-hydroxy-3
      methylglutaryl coenzyme A reductase and phenylalanine ammonia lyase reported
      here. The results are discussed in relation to the proposed role of the 5-LOX in
      signal-response coupling of arachidonate elicitation of the hypersensitive
      response.

PMID- 16653145
TI  - Metabolism of Indole-3-Acetic Acid by Pericarp Discs from Immature and Mature
      Tomato (Lycopersicon esculentum Mill).
AB  - [1'-(14)C, (13)C(6)]Indole-3-acetic acid was infiltrated into immature pericarp
      discs from fruits of tomato (Lycopersicon esculentum Mill., cv Moneymaker). After
      a 24-h incubation period the discs were extracted with methanol and the partially
      purified extract was analyzed by reversed-phase high-performance liquid
      chromatography-radiocounting. Five metabolite peaks (1-5) were detected and
      subsequently analyzed by combined high-performance liquid chromatography-frit
      fast atom bombardment-mass spectrometry. The metabolite 4 fraction was found to
      contain [(13)C(6)]-indole-3-acetylaspartic acid, and analysis of metabolite 5
      identified [(13)C(6)]indole-3-acetyl-beta-d-glucose. The other metabolites could
      not be identified, but alkaline hydrolysis studies and gel permeation
      chromatography indicated that metabolites 1 and 3 were both amide conjugates with
      a molecular weight of approximately 600. Studies with radiolabeled indole-3
      acetic acid, indole-3-acetylaspartic acid, and indole-3-acetyl-beta-d-glucose
      demonstrated that in immature pericarp indole-3-acetic acid is deactivated
      primarily via metabolism to indole-3-acetylaspartic acid, which is further
      converted to metabolites 1, 2, and 3. In mature, pink pericarp discs, indole-3
      acetic acid is converted more extensively to its glucosyl conjugate. Conjugation
      of indole-3-acetic acid to indole-3-acetylaspartic acid appears to be dependent
      upon protein synthesis because it is inhibited by cycloheximide. In contrast,
      cycloheximide has little effect on the further conversion of indole-3
      acetylaspartic acid to metabolites 1, 2, and 3.

PMID- 16653146
TI  - Induction of a Putative Ca-ATPase mRNA in NaCl-Adapted Cells.
AB  - A cDNA clone was isolated that encodes the partial sequence of a putative
      endoplasmic reticulum Ca(2+)-ATPase of tobacco. The 1.497-kb insert had an open
      reading frame of 1.149 kb. The deduced peptide had the greatest homology to the
      endoplasmic reticulum Ca(2+)-ATPases of Drosophila and Artemia, followed by the
      mammalian and avian enzymes (SERCA2 and 3). The cDNA insert hybridized to a
      single mRNA of 4.4 kb from tobacco cultured cells or plant tissues. The level of
      this transcript was induced about 2-fold by NaCl shock in 428 mm NaCl-deadapted
      tobacco cells that were maintained in medium without salt, but not in unadapted
      cells. The level of this transcript was 3- to 4-fold higher in 428 mm NaCl
      adapted cells growing in salt than in unadapted cells growing without salt.

PMID- 16653147
TI  - Inducible phytoalexins in juvenile soybean genotypes predict soybean looper
      resistance in the fully developed plants.
AB  - The hypocotyl of different soybean genotypes was tested for its inducible
      phytoalexin (i.e. glyceollin or coumestrol) accumulation and its inducible
      soybean looper resistance in response to chemical elicitation. A very highly
      insect-resistant soybean genotype (PI 227687) produced significantly more
      phytoalexins than a relatively insect-susceptible one (Davis) in response to the
      same chemical elicitation. The resultant standardized hypocotyl assay allowed
      quick categorization of unknown soybean genotypes regarding the level of insect
      resistance in the fully developed plants. Glyceollin was a better indicator of
      inducible resistance than coumestrol. Elicitor concentration influenced the
      amount of glyceollin and coumestrol accumulated. Younger seedlings (4-5 d old)
      responded stronger to chemical elicitation than did older ones (7-10 d old). The
      elicited accumulation of glyceollin showed a temporal pattern that peaked at 72
      h. Accumulation of coumestrol showed a gradual increase. Elicitation of
      phytoalexins in juvenile soybean plants by sulfhydryl-binding reagents was found
      to be useful for the prediction of genotypic differences in the level of insect
      resistance in the fully developed plants.

PMID- 16653148
TI  - Characterization of a Novel Protein Induced by Progressive or Rapid Drought and
      Salinity in Brassica napus Leaves.
AB  - Under progressive drought stress, Brassica napus displays differential leaf
      modifications. The oldest leaves, developed before the onset of water deficit,
      wilt gradually, whereas the youngest leaves harden. Hardening was distinguished
      by leaf turgor and bluish wax bloom when the shoot water potential was below -3
      MPa and the leaf water saturation deficit was about 60%. This adaptive change was
      accompanied by modifications in two-dimensional protein profiles. Ten percent of
      the polypeptides had altered abundance or were unique to drought-stressed plants.
      Two-dimensional analysis of in vitro translation products did not reveal a
      general decrease in mRNA population. A 22-kD double polypeptide was increased by
      progressive or rapid water stress and salinity and disappeared upon rehydration.
      These polypeptides have a common N-terminal sequence, which does not reveal
      homology with any known water-stress protein but which contains the signature
      motif of soybean Kunitz trypsin inhibitors. Immunoprecipitation allowed these
      polypeptides to be identified on two-dimensional gels of in vitro translation
      products. They appeared to be synthesized as a 24-kD precursor, and their
      transcript was present in the control well-watered leaves, where the polypeptides
      were never detected, indicating a possible translational regulation. A putative
      function of this protein, named BnD22, in the retardation of drought-induced leaf
      senescence is discussed.

PMID- 16653149
TI  - Expression of a ribosomal protein gene in axillary buds of pea seedlings.
AB  - Axillary buds of intact pea seedlings (Pisum sativum L. cv Alaska) do not grow
      and are said to be dormant. Decapitation of the terminal bud promotes the growth
      of these axillary buds, which then develop in the same manner as terminal buds.
      We previously showed that unique sets of proteins are expressed in dormant and
      growing buds. Here we describe the cloning, sequencing, and expression of a cDNA
      clone (pGB8) that is homologous to ribosomal protein L27 from rat. RNA
      corresponding to this clone increases 13-fold 3 h after decapitation, reaches a
      maximum enhancement of about 35-fold after 12 h, and persists at slightly reduced
      levels at later times. Terminal buds, root apices, and elongating internodes also
      contain pGB8 mRNA but fully expanded leaflets and fully elongated internodes do
      not. In situ hybridization analysis demonstrates that pGB8 mRNA increases in all
      parts of the bud within 1 h of decapitation. Under appropriate conditions,
      growing buds can be made to stop growing and become dormant; these buds
      subsequently can grow again. Therefore, buds have the capacity to undergo
      multiple cycles of growth and dormancy. RNA gel blots show that pGB8 expression
      is reduced to dormancy levels as soon as buds stop growing. However, in situ
      hybridization experiments show that pGB8 expression continues at growing-bud
      levels in the apical meristem for 2 d after it is reduced in the rest of the bud.
      When cultured stems containing buds are treated with indoleacetic acid at
      concentrations >/=10 mum, bud growth and expression of pGB8 in the buds are
      inhibited.

PMID- 16653150
TI  - Expression of a Maize Ubiquitin Gene Promoter-bar Chimeric Gene in Transgenic
      Rice Plants.
AB  - We have constructed a chimeric gene consisting of the promoter, first exon, and
      first intron of a maize ubiquitin gene (Ubi-1) and the coding sequence of the bar
      gene from Streptomyces hygroscopicus. This construct was transferred into rice
      (Oryza sativa L.) protoplasts via electroporation, and 10 plants were regenerated
      from calli that had been selected for resistance to exogenously supplied
      bialaphos. Transgenic plants grown in a greenhouse were resistant to both
      bialaphos and phosphinothricine at a dosage lethal to untransformed control
      plants. Evidence of stable integration of the transferred gene into the genome of
      the regenerated primary transformant plants was obtained from Southern blot
      analysis. In addition, northern blot analysis indicated expression and proper
      splicing of the maize ubiquitin gene first intron from the primary chimeric
      transcript in these transgenic rice plants, and western blot analysis and enzymic
      assays verified expression of the active bar gene product. Apparent mendelian
      segregation for bialaphos resistance in T(1) progeny of primary transformants was
      confirmed.

PMID- 16653151
TI  - Appearance of Endoproteolytic Enzymes during the Germination of Barley.
AB  - Barley endoproteolytic enzymes are important to germination because they
      hydrolyze endosperm storage proteins to provide precursors for new protein
      synthesis. We recently developed an electrophoretic method utilizing gel
      incorporated protein substrates to study the endoproteinases of 4-d-germinated
      barley (Hordeum vulgare L. cv Morex) grain. This work extends those findings to
      determine the temporal pattern of the appearance of the endoproteinases during
      germination, the sensitivities of the proteinases to class-specific proteinase
      inhibitors, and where, in germinating caryopses, the proteinases reside. Six
      endoproteinase activity bands (representing a minimum of seven enzymes) were
      present in 5-d-germinated barley grain extracts subjected to electrophoresis in
      nondenaturing gels at pH 8.8. The activities of two of the enzyme bands
      ("neutral" proteinases) increased as the pH was increased from 3.8 to 6.5. The
      activities of the remaining four ("acidic") bands diminished abruptly as the pH
      increased above 4.7. Two proteinase bands hydrolyzed gelatin but not edestin,
      four of the proteinases hydrolyzed both gelatin and edestin at nearly the same
      rates, and one enzyme degraded only edestin. One neutral endoproteinase was
      sensitive to diisopropyl fluorophosphate inhibition, and the other was not
      inhibited by any of inhibitors tested. Four of acidic enzymes were cysteine
      proteinases [inhibited by trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane
      and N-ethylmaleimide]; the other was an aspartic acid endoproteinase (sensitive
      to pepstatin). Only the aspartic proteinase was detected in either ungerminated
      or steeped barley grain. During the germination (malting) process, the aspartic
      endoproteinase activity decreased until the second day of germination and then
      increased until germination day 5. The first endoproteinase(s) induced during
      germination was a neutral enzyme that showed activity on the 1st day of the
      germination phase after steeping. Most of the endoproteinases became active on
      the 2nd or 3rd germination day, but one cysteine proteinase was not detected
      until the 5th day. Acid cysteine proteinases were present in the aleurone,
      scutellum, and endosperm tissues but not in shoots and roots. The aleurone layer
      and endosperm contained almost exclusively band B1 neutral proteinases, whereas
      the scutellum, shoots, and roots contained both B1 and B2 bands. This work shows
      that germinating barley contains a complex set of proteinases whose expression is
      temporally and spatially controlled. But, at the same time, it also shows that
      this electrophoretic method for separating and studying individual enzymes of
      this complex will allow us to more readily characterize and purify them.

PMID- 16653152
TI  - Biochemical Characterization of Photosystem II Antenna Polypeptides in Grana and
      Stroma Membranes of Spinach.
AB  - The photosystem (PS) II antenna system comprises several biochemically and
      spectroscopically distinct complexes, including light-harvesting complex II
      (LHCII), chlorophyll-protein complex (CP) 29, CP26, and CP24. LHCII, the most
      abundant of these, is both structurally and functionally diverse. The
      photosynthetic apparatus is laterally segregated within the thylakoid membrane
      into PSI-rich and PSII-rich domains, and the distribution of antenna complexes
      between these domains has implications for antenna function. We report a detailed
      analysis of the differences in the polypeptide composition of LHCII, CP29, and
      CP26 complexes associated with grana and stroma thylakoid fractions from spinach
      (Spinacia oleracea L.), making use of a very high-resolution denaturing gel
      system, coupled with immunoblots using monospecific antibodies to identify
      specific antenna components. We first show that the polypeptide composition of
      the PSII antenna system is more complex than previously thought. We resolved at
      least five type I LHCII apoproteins and two to three type II LHCII apoproteins.
      We also resolved at least two apoproteins each for CP29 and CP26. In state 1
      adapted grana and stroma thylakoid membranes, the spectrum of LHCII apoproteins
      is surprisingly similar. However, in addition to overall quantitative
      differences, we saw subtle but reproducible qualitative differences in the
      spectrum of LHCII apoproteins in grana and stroma membrane domains, including two
      forms of the major type II apoprotein. The implications of these findings for
      models of PSII antenna function in spinach are discussed.

PMID- 16653153
TI  - Phosphatidylcholine synthesis in castor bean endosperm : free bases as
      intermediates.
AB  - The methylation steps in the biosynthesis of phosphatidylcholine by castor bean
      (Ricinus communis L.) endosperm have been studied by pulse-chase labeling.
      Endosperm halves were incubated with [methyl-(14)C]S-adenosyl-l-methionine, [2
      (14)C]ethanolamine, [(14)C]ethanolamine phosphate, or [(14)C]serine phosphate.
      The kinetics of appearance were followed in the free, phospho-, and phosphatidyl
      bases. The initial methylation utilized ethanolamine as a substrate to form
      methylethanolamine, which was then converted to dimethylethanolamine, choline,
      and phosphomethylethanolamine. Subsequent methylations occurred at the phospho
      base and, to a lesser extent, the phosphatidyl-base levels, after which the
      radioactivity either remained constant or decreased in these compounds and
      accumulated in phosphatidylcholine. Although the precursors tested did support
      the synthesis of choline, the kinetics of the labeling make them unlikely to be
      the major sources of free choline to be utilized for the nucleotide pathway. A
      model with two pools of choline is proposed, and the implications of these
      results for the pathways leading to phosphatidylcholine biosynthesis are
      discussed.

PMID- 16653154
TI  - Phosphatidylcholine Synthesis in Castor Bean Endosperm : Occurrence of an S
      Adenosyl-l-Methionine:Ethanolamine N-Methyltransferase.
AB  - Methylethanolamine synthesis by S-adenosyl-l-methionine:ethanolamine N
      methyltransferase from an extract of castor bean (Ricinus communis L. var Hale)
      endosperm was characterized. The apparent Michaelis-Menten constants of the
      enzyme for ethanolamine and S-adenosyl-l-methionine were estimated to be 6.7 and
      1.4 mum, respectively, although the K(m) for ethanolamine is imprecise because of
      strong substrate inhibition. The pH optimum was 8.0, and a divalent cation was
      required for activity, with Mg(2+) giving the greatest stimulation at 5 mm. The
      enzyme was inhibited by calcium in the micromolar range and relatively high
      concentrations of ethanolamine (above about 7 mum). The activity was found in the
      119,000g supernatant fraction and, therefore, appears to be cytoplasmic. The
      potential roles of S-adenosyl-l-methionine:ethanolamine N-methyltransferase in
      choline and phosphatidylcholine synthesis are discussed.

PMID- 16653155
TI  - Role of Salicylic Acid and Benzoic Acid in Flowering of a Photoperiod-Insensitive
      Strain, Lemna paucicostata LP6.
AB  - Lemna paucicostata LP6 does not normally flower when grown on basal Bonner
      Devirian medium, but substantial flowering is obtained when 10 mum salicylic acid
      (SA) or benzoic acid is added to the medium. Benzoic acid is somewhat more
      effective than SA, and the threshold level of both SA and benzoic acid required
      for flower initiation is reduced as the pH of the medium is lowered to 4.0. SA-
      or benzoic acid-induced flowering is enhanced in the simultaneous presence of 6
      benzylaminopurine (BAP), although BAP per se does not influence flowering in
      strain LP6. Continuous presence of SA or benzoic acid in the culture medium is
      essential to obtain maximal flowering. A short-term treatment of the plants (for
      first 24 h) with 10 mum SA or benzoic acid, followed by culture in the basal
      medium containing 1 mum BAP can, however, stimulate profuse flowering. Benzoic
      acid is more effective than SA, and the effect is more pronounced at pH 4 than at
      5.5. Thus, under these conditions, flowering is of an inductive nature.
      Experiments with [(14)C]SA and [(14)C]benzoic acid have provided evidence that at
      pH 4 there is relatively more uptake of benzoic acid than SA, thus leading to an
      increased flowering response. The data obtained from the experiments designed to
      study the mobility of [(14)C]SA and [(14)C]-benzoic acid from mother to daughter
      fronds indicate that there is virtually no mobility of SA or benzoic acid between
      fronds.

PMID- 16653156
TI  - Light dependence of catalase synthesis and degradation in leaves and the
      influence of interfering stress conditions.
AB  - The enzyme catalase (EC 1.11.1.6) is light sensitive and subject to a rapid
      turnover in light, similar to the D1 reaction center protein of photosystem II.
      After 3 h of preadaptation to darkness or to different light intensities (90 and
      520 mumol m(-2) s(-1) photosynthetic photon flux density), sections of rye leaves
      (Secale cereale L.) were labeled for 4 h with l-[(35)S]methionine. From leaf
      extracts, catalase was immunoprecipitated with an antiserum prepared against the
      purified enzyme from rye leaves. Both incorporation into catalase and degradation
      of the enzyme polypeptide during a subsequent 16-h chase period increased with
      light intensity. At a photon flux density of 520 mumol m(-2) s(-1), the apparent
      half-time of catalase in rye leaves was 3 to 4 h, whereas that of the D1 protein
      was much shorter, about 1.5 h. Exposure to stress conditions, such as 0.6 m NaCl
      or a heat-shock temperature of 40 degrees C, greatly suppressed both total
      protein synthesis and incorporation of the label into catalase and into the D1
      protein. Immunoblotting assays indicated that in light, but not in darkness,
      steady-state levels of catalase and of the D1 protein strongly declined during
      treatments with salt, heat shock, or translation inhibitors that block repair
      synthesis. Because of the common property of rapid photodegradation and the
      resulting dependence on continuous repair, declines in catalase as well as of the
      D1 protein represent specific and sensitive indicators for stress conditions that
      suppress the translational activities of leaves.

PMID- 16653157
TI  - Photoinactivation of Catalase Occurs under Both High- and Low-Temperature Stress
      Conditions and Accompanies Photoinhibition of Photosystem II.
AB  - Severe photoinactivation of catalase (EC 1.11.1.6) and a decline of variable
      fluorescence (F(v)), indicating photoinhibition of photosynthesis, were observed
      as rapid and specific symptoms in leaves exposed to a high heat-shock temperature
      of 40 degrees C as well as in leaves exposed to low chilling temperatures in
      white light of only moderately high photosynthetic photon flux density of 520 muE
      m(-2) s(-1). Other parameters, such as peroxidase (EC 1.11.1.7), glycolate
      oxidase (EC 1.1.3.1), glutathione reductase (EC 1.6.4.2), or the chlorophyll
      content, were hardly affected under these conditions. At a compatible temperature
      of 22 degrees C, the applied light intensity did not induce severe
      photoinactivations. In darkness, exposures to high or low temperatures did not
      affect catalase levels. Also, decline of F(v) in light was not related to
      temperature sensitivity in darkness. The effective low-temperature ranges
      inducing photoinactivation of catalase differed significantly for chilling
      tolerant and chilling-sensitive plants. In leaves of rye (Secale cereale L.) and
      pea (Pisum sativum L.), photoinactivation occurred only below 15 degrees C,
      whereas inactivation occurred at 15 degrees C in cucumber (Cucumis sativus L.)
      and maize (Zea mays L.). The behavior of F(v) was similar, but the difference
      between chilling-sensitive and chilling-tolerant plants was less striking.
      Whereas the catalase polypeptide, although photoinactivated, was not cleaved at 0
      to 4 degrees C, the D1 protein of photosystem II was greatly degraded during the
      low-temperature treatment of rye leaves in light. Rye leaves did not exhibit
      symptoms of any major general photodamage, even when they were totally depleted
      of catalase after photoinactivation at 0 to 4 degrees C, and catalase recovered
      rapidly at normal temperature. In cucumber leaves, the decline of catalase after
      exposures to bright light at 0 to 4 degrees C was accompanied by bleaching of
      chlorophyll, and the recovery observed at 25 degrees C was slow and required
      several days. Similar to the D1 protein of photosystem II, catalase differs
      greatly from other proteins by its inactivation and high turnover in light.
      Inasmuch as catalase and D1 protein levels depend on continuous repair synthesis,
      preferential and rapid declines are generally to be expected in light whenever
      translation is suppressed by stress actions, such as heat or chilling, and
      recovery will reflect the repair capacity of the plants.

PMID- 16653158
TI  - Fast Fluorescence Quenching from Isolated Guard Cell Chloroplasts of Vicia faba
      Is Induced by Blue Light and Not by Red Light.
AB  - Chlorophyll a fluorescence transients from isolated Vicia faba guard cell
      chloroplasts were used to probe the response of these organelles to light
      quality. Guard cell chloroplasts were isolated from protoplasts by passing them
      through a 10-mum nylon net. Intact chloroplasts were purified on a Percoll
      gradient. Chlorophyll a fluorescence transients induced by actinic red or blue
      light were measured with a fluorometer equipped with a measuring beam. Actinic
      red light induced a monophasic quenching, and transients induced by blue light
      showed biphasic kinetics having a slow and a fast component. The difference
      between the red and blue light-induced transients could be observed over a range
      of fluence rates tested (200-800 mumol m(-2) s(-1)). The threshold fluence rate
      of blue light for the induction of the fast component of quenching was 200 mumol
      m(-2) s(-1), but in the presence of saturating red light, fluence rates as low as
      25 mumol m(-2) s(-1) induced the fast quenching. These results indicate that
      guard cell chloroplasts have a specific response to blue light.

PMID- 16653159
TI  - Vanadate inhibits blue light-stimulated swelling of vicia guard cell protoplasts.
AB  - When supplied under low chloride concentrations, vanadate inhibits the blue light
      stimulated swelling of Vicia faba L. guard cell protoplasts in a dose-dependent
      fashion. The volume of guard cell protoplasts incubated in 10 mm K-imino-diacetic
      acid, 0.4 m mannitol, and 1 mm CaCl(2) remained essentially constant under 1000
      mumol m(-2) s(-1) red light, but increased an average of 27% after 8 min of the
      addition of 50 mumol m(-2) s(-1) blue light to the background red light. At 500
      mum, vanadate completely inhibits the response to blue light. Vanadate also
      inhibits the swelling of guard cell protoplasts stimulated by the H(+)-ATPase
      agonist fusicoccin. The vanadate sensitivity of the blue light-stimulated
      swelling implicates a proton-pumping ATPase as a component of the sensory
      transduction of blue light in guard cells.

PMID- 16653160
TI  - Estimation of Ammonium Ion Distribution between Cytoplasm and Vacuole Using
      Nuclear Magnetic Resonance Spectroscopy.
AB  - Evidence is presented that intracellular ammonium is trapped in vacuoles of maize
      (Zea mays L.) root tips because of rapid movement of ammonia between cytoplasm
      and vacuoles. The concentration of cytoplasmic ammonium is estimated to be <15
      mum at extracellular ammonium concentrations up to 1 mm. The implications for
      pathways of ammonium assimilation are discussed.

PMID- 16653161
TI  - Intracellular Localization of Three l-Glutamate Dehydrogenase Isozymes from
      Chlamydomonas reinhardtii.
AB  - The intracellular localization of the activity and synthesis of three isozymes of
      NAD(P)(+)-glutamate dehydrogenase from the unicellular green alga Chlamydomonas
      reinhardtii cw-92 has been established. Isozyme activities have been located
      within mitochondria by using differential centrifugation techniques and
      discontinuous Percoll gradient separations. Experiments with protein synthesis
      inhibitors cycloheximide, rifampicin, chloramphenicol, and actinomycin D, under
      dark and carbon starvation conditions, revealed that synthesis of the three
      isozymes was likely to occur in cytosol as precursor proteins that are then
      transported and processed inside the mitochondria.

PMID- 16653162
TI  - Purification and characterization of cytosolic 6-phosphogluconate dehydrogenase
      isozymes from maize.
AB  - Cytosolic isozymes of 6-phosphogluconate dehydrogenase were purified from roots
      of maize (Zea mays L.). The final preparation contained two 55-kD proteins.
      Affinity-purified dehydrogenases from a maize line that is null for both
      cytosolic 6-phosphogluconate dehydrogenase isozymes (Pgd1-null, Pgd2-null) lacked
      the 55-kD proteins. The substrate kinetics of the purified enzyme were
      determined.

PMID- 16653163
TI  - In situ nuclear magnetic resonance of N pulse labels monitors different routes
      for nitrogen assimilation.
AB  - Nuclear magnetic resonance offers the possibility of noninvasive in situ
      observation of (15)N pulse labeling in the presence of light. In vivo,
      exclusively the delta-nitrogen of Gln is labeled in the cyanobacterium
      Microcystis firma when glutamate synthase is inhibited by azaserine. In contrast,
      the green alga Chlorella fusca is additionally capable of incorporating nitrogen
      into Glu, thus providing evidence for an anabolic function of glutamate
      dehydrogenase in this organism.

PMID- 16653164
TI  - Intact Leaves Exhibit a Climacteric-Like Rise in Ethylene Production before
      Abscission.
AB  - The rate of ethylene production by intact, attached leaves of cotton plants
      (Gossypium hirsutum L.) during aging and senescence was studied using a
      continuous flow system that allowed air around enclosed leaves to be scrubbed to
      collect and assay ethylene. Senescence of lower leaves began around 150 d after
      planting in a controlled environment room. A progressive decline in the ethylene
      production rate was observed when comparing the 3rd, 6th, and 10th leaves from
      the base with each other. Ethylene production rates of individual leaves also
      declined over a 50-d period. However, as leaves began to appear chlorotic, a peak
      of ethylene production occurred that lasted for about 4 d followed by abscission.
      This peak involved a 3-fold or greater increase in the rate of ethylene
      production. The data indicate that intact leaves experience a climacteric-like
      surge in ethylene production after visible symptoms of senescence appear. This
      "ethylene climacteric" is apparently the signal that initiates hydrolysis of cell
      walls in the abscission zone.

PMID- 16653165
TI  - Detection of a Cytosolic Glutamine Synthetase in Leaves of Nicotiana tabacum L.
      by Immunocytochemical Methods.
AB  - Two glutamine synthetase (GS) polypeptides (44 and 39 kD) were immunodetected on
      western blots of leaf extracts from tobacco (Nicotiana tabacum L.), a plant that
      has been reported to contain only chloroplast GS in the leaves. By
      immunocytochemical methods, we confirmed the localization of GS in the cytosol of
      cells in the vascular tissue and in the chloroplasts of mesophyll cells.

PMID- 16653166
TI  - Differential temperature sensitivity of pea superoxide dismutases.
AB  - The activity of pea (Pisum sativum L.) Cu/Zn and Mn superoxide dismutase isoforms
      was evaluated across a range of temperatures from 10 to 45 degrees C. Maximal
      activity of the Cu/Zn and Mn superoxide dismutase isoforms was observed at 10
      degrees C. Both cytoplasmic and chloroplast Cu/Zn superoxide dismutases exhibit a
      reduction in staining intensity with increasing temperatures. Mn superoxide
      dismutase, however, maintained a relatively constant staining intensity across
      the range of temperatures evaluated. An unrelated enzyme used as a control,
      malate dehydrogenase, exhibited the expected increase in staining activity with
      increasing temperatures. These results describe a unique response of a protection
      enzyme to temperature.

PMID- 16653167
TI  - Evidence against the Regulation of Grain Set by Spikelet Abscisic Acid Levels in
      Water-Stressed Wheat.
AB  - A possible role of abscisic acid (ABA) in the regulation of grain set in water
      stressed wheat (Triticum aestivum L.) was investigated using a split root system
      to dry half the roots while the remainder were kept watered. Water uptake by the
      wet roots maintained the leaf water potential at the normal level, whereas the
      ABA produced in the dry roots was transported to the spike. This caused the
      spikelet ABA level to increase to the same extent as when the entire root system
      was stressed to permit a drop in the leaf water potential. In spite of this, the
      former treatment did not induce a reduction in grain set, whereas the latter did.
      Thus, contrary to previous reports, water stress-induced changes in spikelet ABA
      level alone do not appear to regulate grain set.

PMID- 16653168
TI  - The Extensin from Prunus amygdalus.

PMID- 16653169
TI  - Molecular cloning and nucleotide sequence of a cDNA encoding catalase from
      tomato.

PMID- 16653170
TI  - Nucleotide Sequence of a cDNA Encoding NADP-Sorbitol-6-Phosphate Dehydrogenase
      from Apple.

PMID- 16653171
TI  - Deduced amino Acid sequence of a plant cDNA containing a leucine zipper motif.

PMID- 16653172
TI  - Complementary DNA cloning and sequence analysis of a pathogen-induced putative
      peroxidase from rice.

PMID- 16653173
TI  - Nucleotide Sequence of a cDNA Encoding 3-Hydroxy-3-Methylglutaryl Coenzyme A
      Reductase from Catharanthus roseus.

PMID- 16653174
TI  - Nucleotide Sequence of the Nicotiana tabacum cv Xanthi Gene Encoding 1
      Aminocyclopropane-1-Carboxylate Synthase.

PMID- 16653175
TI  - ADP-Glucose Pyrophosphorylase Large Subunit cDNA from Barley Endosperm.

PMID- 16653176
TI  - Concerning a dual function of coupled cyclic electron transport in leaves.
AB  - Coupled cyclic electron transport is assigned a role in the protection of leaves
      against photoinhibition in addition to its role in ATP synthesis. In leaves, as
      in reconstituted thylakoid systems, cyclic electron transport requires "poising,"
      i.e. availability of electrons at the reducing side of photosystem I (PSI) and
      the presence of some oxidized plastoquinone between photosystem II (PSII) and
      PSI. Under self-regulatory poising conditions that are established when carbon
      dioxide limits photosynthesis at high light intensities, and particularly when
      stomata are partially or fully closed as a result of water stress, coupled cyclic
      electron transport controls linear electron transport by helping to establish a
      proton gradient large enough to decrease PSII activity and electron flow to PSI.
      This brings electron donation by PSII, and electron consumption by available
      electron acceptors, into a balance in which PSI becomes more oxidized than it is
      during fast carbon assimilation. Avoidance of overreduction of the electron
      transport chain is a prerequisite for the efficient protection of the
      photosynthetic apparatus against photoinactivation.

PMID- 16653177
TI  - Nuclear targeting in plants.

PMID- 16653178
TI  - The Expression Pattern of the Tonoplast Intrinsic Protein gamma-TIP in
      Arabidopsis thaliana Is Correlated with Cell Enlargement.
AB  - The vacuolar membrane (tonoplast) contains an abundant intrinsic protein with six
      membrane-spanning domains that is encoded by a small gene family. Different
      isoforms of tonoplast intrinsic protein (TIP) are expressed in different tissues
      or as a result of specific signals. Using promoter-beta-glucuronidase (GUS)
      fusions and in situ hybridization, we have examined the expression of gamma-TIP
      in Arabidopsis thaliana. GUS staining of plants transformed with promoter-GUS
      fusions showed that gamma-TIP gene expression is high in recently formed tissues
      of young roots. In the shoot, gamma-TIP gene expression was highest in the
      vascular bundles of stems and petioles, as well as in the stipules and in the
      receptacle of the flower. No GUS activity was detected in root or shoot meristems
      or in older tissues, suggesting temporal control of gamma-TIP gene expression
      associated with cell elongation and/or differentiation. In situ hybridization
      carried out with whole seedlings confirmed that in root tips, gamma-TIP mRNA was
      present only in the zone of cell elongation just behind the apical meristem. In
      seedling shoots, mRNA abundance was also found to be correlated with cell
      expansion. These results indicate that gamma-TIP may be expressed primarily at
      the time when the large central vacuoles are being formed during cell
      enlargement.

PMID- 16653179
TI  - Sink to Source Transition in Tendrils of a Semileafless Mutant, Pisum sativum cv
      Curly.
AB  - Sink to source transition parallels loss of thigmotropic capacity in tendrils of
      a semileafless mutant, Pisum sativum cv Curly. Macroscopic tendril development is
      subdivided based on thigmotropic capacity. Stage I is the elongation stage and,
      although the rate of photosynthesis is similar to that of stage II and III
      tendrils, dark respiration rates are higher in stage I. During stage II, tendrils
      are thigmotropic and act as a sink. Even though stage II tendrils have CO(2)
      exchange characteristics similar to those of stage III tendrils, which are
      coiled, our fluorescein, (14)C-partitioning, and (11)C-translocation experiments
      suggest that stage I and II tendrils do not export carbon. Only stage III
      tendrils act as sources of newly fixed carbon. Export from them is blocked by
      cold, heat girdling of the petiole, or anoxia treatment of the tendrils. A late
      stage II tendril complex, in which coiling is occurring, may be exporting
      photoassimilates; however, this phenomenon can be attributed to the fact that the
      pea leaf is a compound structure and there may be one or more stage III tendrils,
      no longer thigmotropic, within the tendril complex. Photosynthetic maturity in
      pea tendrils occurs at stage III and is characterized by the ability of these
      tendrils to export photoassimilates.

PMID- 16653180
TI  - The PsENOD12 Gene Is Expressed at Two Different Sites in Afghanistan Pea
      Pseudonodules Induced by Auxin Transport Inhibitors.
AB  - A number of early nodulin genes are expressed in specific cell types as pea
      (Pisum sativum) root nodules develop. The Pisum sativum early nodulin PsENOD2 is
      detected only in the uninfected cells of the nodule parenchyma, whereas PsENOD12
      is expressed at two spatially removed sites: in root hairs and adjacent cortical
      cells, both of which can be invaded by Rhizobium entering through infection
      threads, and in derivatives of newly divided root inner cortical cells that
      establish the nodule primordium. We tested whether Rhizobium infection is
      required for triggering PsENOD12 gene expression by inducing nodule-like
      structures on Afghanistan pea roots with the auxin transport inhibitor N-(1
      naphthyl)phthalamic acid (NPA). These nodule-like structures lack infection
      threads but resemble Rhizobium-induced nodules in other aspects. For one, both
      PsENOD2 and PsENOD12 transcripts were detected in these structures. PsENOD2 mRNA
      was localized by in situ hybridization to a zone equivalent to the nodule
      parenchyma of Rhizobium-induced nodules, whereas PsENOD12 transcripts were
      detected in a group of cells comparable to the nodule primordium of developing
      nodules. In addition, PsENOD12 mRNA was detected in uninfected root hairs 48 h
      after NPA treatment. These results indicate that infection is not a trigger for
      PsENOD12 gene expression in Afghanistan pea and rather suggest that the
      expression of the PsENOD2 and PsENOD12 genes is correlated with the
      differentiation of specific cell types in the developing nodule.

PMID- 16653181
TI  - Delay of Membrane Lipid Degradation by Calcium Treatment during Cabbage Leaf
      Senescence.
AB  - Cabbage leaf discs (Brassica oleracea L., Capitata group) were floated adaxial
      side up in 0, 0.05, or 0.25 m CaCl(2) solutions at 15 degrees C for 14 d in the
      dark. To assess whether the delay of senescence by calcium treatment involved
      protection of membrane lipids, chlorophyll and protein content and the lipid
      composition of the membranes were determined during incubation. Chlorophyll and
      protein content decreased with time, in correlation with a reduction in the
      amount of phospholipids. The degree of unsaturation of phospholipids and free
      fatty acids decreased, whereas the ratio of sterol to phospholipid increased. The
      proportions of phospholipid classes did not change during senescence. The
      catabolism of phospholipids was delayed by 0.05 m calcium, but accelerated by
      0.25 m, as compared to the untreated control. Based on the levels of the lipid
      intermediates, phospholipase D, phosphatidic acid phosphatase, lipolytic acyl
      hydrolase, and lipoxygenase appeared to be involved in the breakdown of
      phospholipids during senescence. Phospholipase D and phosphatidic acid
      phosphatase may be directly influenced by calcium. The calcium treatment
      apparently did not affect the activity of acyl hydrolase. Lipoxygenase,
      responsible for the peroxidation of the polyunsaturated fatty acids, was probably
      indirectly influenced by calcium. We conclude that the delay of senescence of
      cabbage leaf discs by calcium treatment involved protection of membrane lipids
      from degradation.

PMID- 16653182
TI  - Identification, cDNA Cloning, and Analysis of mRNAs Having Altered Expression in
      Tips of Harvested Asparagus Spears.
AB  - Changes in mRNA activity in tips of harvested asparagus spears (Asparagus
      officinalis L.) held in light or dark for up to 48 h at 20 degrees C were
      investigated as an initial step in elucidating the genetic response of asparagus
      spears to harvest. Total RNA was isolated from 30-mm tips of spears 180 mm in
      length at 0, 6, 12, 24, and 48 h after spear harvest and translated in vitro, and
      translation products were separated using both sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and two-dimensional polyacrylamide gel
      electrophoresis. We detected 25 consistent changes in translatable mRNAs,
      involving both increase and decrease in mRNA abundance. The majority of the
      changes occurred within 12 h of harvest. Most of the changes were not light
      regulated. cDNA libraries were constructed from polyadenylated mRNA extracted
      from tips of spears at harvest (0 h) and after 12 h in the dark at 20 degrees C.
      Differential hybridization screening of the cDNA libraries isolated nine cDNA
      clones whose corresponding transcripts had altered expression after harvest.
      Investigations of mRNA activity during spear development demonstrated that the
      changes detected were harvest related. Possible roles for the mRNAs corresponding
      to the isolated clones in tips of harvested spears are discussed.

PMID- 16653183
TI  - Reconstitution and Characterization of a Calmodulin-Stimulated Ca-Pumping ATPase
      Purified from Brassica oleracea L.
AB  - Purification and functional reconstitution of a calmodulin-stimulated Ca(2+)
      ATPase from cauliflower (Brassica oleracea L.) is described. Activity was
      purified about 120-fold from a microsomal fraction using calmodulin-affinity
      chromatography. The purified fraction showed a polypeptide at 115 kD, which
      formed a phosphorylated intermediate in the presence of Ca(2+), together with a
      few polypeptides with lower molecular masses that were not phosphorylated. The
      ATPase was reconstituted into liposomes by 3-([cholamidopropyl]-dimethylammonio
      )1-propanesulfonate (CHAPS) dialysis. The proteoliposomes showed ATP-dependent
      Ca(2+) uptake and ATPase activity, both of which were stimulated about 4-fold by
      calmodulin. Specific ATPase activity was about 5 mumol min(-1) (mg protein)(-1),
      and the Ca(2+)/ATP ratio was 0.1 to 0.5 when the ATPase was reconstituted with
      entrapped oxalate. The purified, reconstituted Ca(2+)-ATPase was inhibited by
      vanadate and erythrosin B, but not by cyclopiazonic acid and thapsigargin.
      Activity was supported by ATP (100%) and GTP (50%) and had a pH optimum of about
      7.0. The effect of monovalent and divalent cations (including Ca(2+)) on activity
      is described. Assay of membranes purified by two-phase partitioning indicated
      that approximately 95% of the activity was associated with intracellular
      membranes, but only about 5% with plasma membranes. Sucrose gradient
      centrifugation suggests that the endoplasmic reticulum is the major cellular
      location of calmodulin-stimulated Ca(2+)-pumping ATPase in Brassica oleracea
      inflorescences.

PMID- 16653184
TI  - P relaxation responses associated with n(2)/o(2) diffusion in soybean nodule
      cortical cells and excised cortical tissue.
AB  - N(2)-fixing Bradyrhizobium japonicum nodules and cortical tissue derived from
      these nodules were examined in vivo by (31)P nuclear magnetic resonance (NMR)
      spectroscopy. Perfusion of the viable nodules and excised cortical tissue with
      O(2) followed by N(2) or Ar caused a loss of orthophosphate (Pi) resonance
      magnetization associated with the major portion of acidic Pi (delta 0.9 ppm, pH
      5.5) residing in the cortical cells. Resumption of O(2) perfusion restored
      approximately 80% of the intensity of this peak. Detailed examination of the
      nuclear relaxation processes, spin-lattice relaxation time (T(1)), and spin-spin
      relaxation time (T(2)), under perfusion with N(2) or Ar as opposed to O(2),
      indicated that loss of signal was due to T(1) saturation of the acidic Pi signal
      under the rapid-pulsed NMR recycling conditions. In excised cortical tissue, Pi
      T(1), values derived from biexponential relaxation processes under perfusing O(2)
      were 59% 3.72 +/- 0.93 s and 41% 0.2 +/- 0.08 s, whereas under N(2) these values
      were 85% 7.07 +/- 1.36 s and 15% 0.39 +/- 0.07 s. The T(1) relaxation behavior of
      whole nodule vacuolar Pi showed the same trend, but the overall values were
      somewhat shorter. T(2) values for cortical tissue were also biexponential but
      were essentially the same under O(2) (38% 0.066 +/- 0.01 s and 63% 0.41 +/- 0.08
      s) and N(2) (39% 0.07 +/- 0.01 s and 61% 0.37 +/- 0.01 s) perfusion. Soybean
      (Glycine max) root tissue as well as Pi solutions exhibited single exponential
      T(1) decay values that were not altered by changes in the perfusing gas. These
      data indicate that oxygen induces a change in the physical environment of
      phosphate in the cortical cell tissue. Although under certain conditions oxygen
      has been observed to act as a paramagnetic relaxation agent, model T(1)
      experiments demonstrate that O(2) does not significantly influence Pi relaxation
      in this manner. Alternatively, we suggest that an increase in solution viscosity
      brought on by the production of an occlusion glycoprotein (under O(2) perfusion)
      is responsible for the observed relaxation changes.

PMID- 16653185
TI  - Observation of the Oxygen Diffusion Barrier in Soybean (Glycine max) Nodules with
      Magnetic Resonance Microscopy.
AB  - The effects of selected gas perfusion treatments on the spinlattice relaxation
      times (T(1)) of the soybean (Glycine max) nodule cortex and inner nodule tissue
      were studied with (1)H high resolution magnetic resonance microscopy. Three gas
      treatments were used: (a) perfusion with O(2) followed by N(2); (b) O(2) followed
      by O(2); and (c) air followed by N(2). Soybean plants with intact attached
      nodules were placed into the bore of a superconducting magnet and a selected root
      with nodules was perfused with the gas of interest. Magnetic resonance images
      were acquired with repetition times from 50 to 3200 ms. The method of partial
      saturation was used to calculate T(1) times on selected regions of the image.
      Calculated images based on T(1) showed longer T(1) values in the cortex than in
      the inner nodule during all of the gas perfusions. When nodules were perfused
      with O(2)-O(2), there was no significant change in the T(1) of the nodule between
      the two gas treatments. When the nodule was perfused with O(2)-N(2) or air-N(2),
      however, the T(1) of both the cortex and inner nodule increased. In these
      experiments, the increase in T(1) of the cortex was 2- to 3-fold greater than the
      increase observed in the inner nodule. A similar change in T(1) was found in
      detached live nodules, but there was no change in T(1) with selective gas
      perfusion of detached dead nodules. These observations suggest that cortical
      cells respond differently to selected gas perfusion than the inner nodule, with
      the boundary of T(1) change sharply delineated at the interface of the inner
      nodule and the inner cortex.

PMID- 16653186
TI  - Kinetics of the Vacuolar H-Pyrophosphatase : The Roles of Magnesium,
      Pyrophosphate, and their Complexes as Substrates, Activators, and Inhibitors.
AB  - The responses of the vacuolar membrane (tonoplast) proton-pumping inorganic
      pyrophosphatase (H(+)-PPase) from oat (Avena sativa L.) roots to changes in
      Mg(2+) and pyrophosphate (PPi) concentrations have been characterized. The
      kinetics were complex, and reaction kinetic models were used to determine which
      of the various PPi complexes were responsible for the observed responses. The
      results indicate that the substrate for the oat root vacuolar H(+)-PPase is
      Mg(2)PPi and that this complex is also a non-competitive inhibitor. In addition,
      the enzyme is activated by free Mg(2+) and competitively inhibited by free PPi.
      This conclusion differs from that reached in previous studies, in which it was
      proposed that MgPPi is the substrate for plant vacuolar H(+)-PPases. However,
      models incorporating MgPPi as a substrate were unable to describe the kinetics of
      the oat H(+)-PPase. It is demonstrated that models incorporating Mg(2)PPi as the
      substrate can describe some of the published kinetics of the Kalanchoe
      daigremontiana vacuolar H(+)-PPase. Calculations of the likely concentrations of
      Mg(2)PPi in plant cytoplasm suggest that the substrate binding site of the oat
      vacuolar H(+)-PPase would be about 70% saturated in vivo.

PMID- 16653187
TI  - Regulation of vacuolar h-pyrophosphatase by free calcium : a reaction kinetic
      analysis.
AB  - The H(+)-translocating inorganic pyrophosphatase (H(+)-PPase) associated with
      vesicles of the vacuolar membrane (tonoplast) isolated from beet (Beta vulgaris
      L.) is subject to direct inhibition by Ca(2+) and a number of other divalent
      cations (Co(2+), Mn(2+), Zn(2+)). By contrast, the H(+)-translocating ATPase
      (H(+)-ATPase) located on the same membrane is insensitive to Ca(2+). Here we
      examine the mechanism and feasibility of regulation of the vacuolar H(+)-PPase by
      cytosolic free Ca(2+) under the conditions thought to prevail in vivo with
      respect to Mg(2+), inorganic pyrophosphate (PPi), and pH. The minimal reaction
      scheme that satisfactorily describes the effects of elevated Ca(2+) or CaPPi on
      the enzyme is one that invokes equilibrium binding of substrate (Mg(2)PPi) at one
      site, inhibitory binding of Mg(2)PPi to a lower-affinity second site, binding of
      activator (Mg(2+)) at a third site, and direct binding of Ca(2+) or CaPPi to a
      fourth site. Changes in enzyme activity in response to selective manipulation of
      either Ca(2+) or CaPPi are explicable only if Ca(2+), rather than CaPPi, is the
      inhibitory ligand. This conclusion is supported by the finding that CaPPi fails
      to mimic substrate in protection of the enzyme from inhibition by N
      ethylmaleimide. Furthermore, the reaction scheme quantitatively and independently
      predicts the observed noncompetitive effects of free Ca(2+) on the substrate
      concentration dependence of H(+)-PPase activity. The results are discussed in
      relation to the previous proposal that CaPPi is the principal inhibitory ligand
      of the vacuolar H(+)-PPase (M. Maeshima [1991] Eur J Biochem 196: 11-17) and the
      possibility that in vivo modulation of cytosolic free Ca(2+) might constitute a
      specific mechanism for selective regulation of this enzyme, and consequently for
      stabilization of PPi levels in the cytoplasm of plant cells.

PMID- 16653188
TI  - The Isolation of Actin from Pea Roots by DNase I Affinity Chromatography.
AB  - Native actin can be isolated from pea (Pisum sativum L.) roots by DNase I
      affinity chromatography, but the resulting yields and quality of actin are
      variable. By use of two assays for actin, a DNase I inhibition assay and a gel
      scanning assay, we identified several factors that increased actin yield. ATP is
      required for the actin in crude pea root extracts to bind to immobilized DNase I.
      Low amounts of ATP are hydrolyzed rapidly by an endogenous ATPase in the extract,
      and the actin then irreversibly loses the ability to bind to DNase I. High ATP
      concentrations (5-10 mm) or inhibition of the ATPase (with 10 mm pyrophosphate)
      are required for pea actin to retain DNase I binding ability. When adequate
      amounts of ATP are present, actin binding from the extract is further enhanced by
      basic pH, formamide, and soluble polyvinyl-pyrrolidone. Once actin is bound to
      the DNase I-agarose and washed free of extract, high ATP concentrations are not
      required to keep actin bound. Actin eluted from the DNase I-agarose with
      formamide retained its ability to polymerize into filaments with the addition of
      KCl and Mg(2+). The advantages and disadvantages of this procedure and its
      application to other plant materials are discussed.

PMID- 16653189
TI  - Changes in Cytokinin Activities and Mass Spectrometric Analysis of Cytokinins in
      Root Exudates of Rice Plant (Oryza sativa L.) : Comparison between Cultivars
      Nipponbare and Akenohoshi.
AB  - Changes in exudation rate and cytokinin activities in the exudates were measured
      in two varieties of rice (Oryza sativa L.), cv Nipponbare (a Japanese normal
      cultivar) and cv Akenohoshi (a high-yielding cultivar). The exudation rates of
      Akenohoshi, the leaves of which remained green for a longer time, were higher
      than those of Nipponbare after the booting stage. Cytokinin activities in the
      exudates of Akenohoshi were higher than those of Nipponbare during the ripening
      period. Cytokinins in the exudates collected during the middle of the ripening
      stage were analyzed with mass spectrometry using deuterium-labeled standards.
      trans-Zeatin, trans-ribosylzeatin, and N(6)-isopentenyladenosine were detected as
      free cytokinins, and zeatin was detected in the hydrolysates of highly polar
      fractions ("conjugated zeatin") in the exudates of both cultivars. Conjugated
      zeatin was the predominant cytokinin in both cultivars. Therefore, we suggest
      that conjugated zeatin is an important form of cytokinin during the ripening
      stage. The level of each of the cytokinins in Akenohoshi was higher than that in
      Nipponbare. Also, we discuss the correlation between the leaf senescence and
      cytokinin content in root exudates.

PMID- 16653190
TI  - Expression of a bacterial ice nucleation gene in plants.
AB  - We have introduced an ice nucleation gene (inaZ) from Pseudomonas syringae pv.
      syringae into Nicotiana tabacum, a freezing-sensitive species, and Solanum
      commersonii, a freezing-tolerant species. Transformants of both species showed
      increased ice nucleation activity over untransformed controls. The concentration
      of ice nuclei detected at -10.5 degrees C in 15 different primary transformants
      of S. commersonii varied by over 1000-fold, and the most active transformant
      contained over 100 ice nuclei/mg of tissue. The temperature of the warmest
      freezing event in plant samples of small mass was increased from approximately 
      12 degrees C in the untransformed controls to -4 degrees C in inaZ-expressing
      transformants. The threshold nucleation temperature of samples from transformed
      plants did not increase appreciably with the mass of the sample. The most
      abundant protein detected in transgenic plants using immunological probes
      specific to the inaZ protein exhibited a higher mobility on sodium dodecyl
      sulfate polyacrylamide gels than the inaZ protein from bacterial sources.
      However, some protein with a similar mobility to the inaZ protein could be
      detected. Although the warmest ice nucleation temperature detected in transgenic
      plants is lower than that conferred by this gene in P. syringae (-2 degrees C),
      our results demonstrate that the ice nucleation gene of P. syringae can be
      expressed in plant cells to produce functional ice nuclei.

PMID- 16653191
TI  - Distinctive Responses of Ribulose-1,5-Bisphosphate Carboxylase and Carbonic
      Anhydrase in Wheat Leaves to Nitrogen Nutrition and their Possible Relationships
      to CO(2)-Transfer Resistance.
AB  - The amounts of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), total
      chlorophyll (Chl), and total leaf nitrogen were measured in fully expanded, young
      leaves of wheat (Triticum aestivum L.), rice (Oryza sativa L.), spinach (Spinacia
      oleracea L.), bean (Phaseolus vulgaris L.), and pea (Pisum sativum L.). In
      addition, the activities of whole-chain electron transport and carbonic anhydrase
      were measured. All plants were grown hydroponically at different nitrogen
      concentrations. Although a greater than proportional increase in Rubisco content
      relative to leaf nitrogen content and Chl was found with increasing nitrogen
      supply for rice, spinach, bean, and pea, the ratio of Rubisco to total leaf
      nitrogen or Chl in wheat was essentially independent of nitrogen treatment. In
      addition, the ratio of Rubisco to electron transport activities remained constant
      only in wheat. Nevertheless, gas-exchange analysis showed that the in vivo
      balance between the capacities of Rubisco and electron transport in wheat, rice,
      and spinach remained almost constant, irrespective of nitrogen treatment. The in
      vitro carbonic anhydrase activity in wheat was very low and strongly responsive
      to increasing nitrogen content. Such a response was not found for the other C(3)
      plants examined, which had 10- to 30-fold higher carbonic anhydrase activity than
      wheat at any leaf-nitrogen content. These distinctive responses of carbonic
      anhydrase activity in wheat were discussed in relation to CO(2)-transfer
      resistance and the in vivo balance between the capacities of Rubisco and electron
      transport.

PMID- 16653192
TI  - Identification of Embryoid-Abundant Genes That Are Temporally Expressed during
      Pollen Embryogenesis in Wheat Anther Cultures.
AB  - Uninucleate microspores in anther cultures of bread wheat (Triticum aestivum cv
      Pavon) are capable of producing haploid pollen embryoids and plants. To gain an
      understanding of this alternate pathway of pollen development, we constructed a
      cDNA library to young pollen embryoids, isolated embryoid-specific genes, and
      analyzed their expression patterns during morphogenesis. Two embryoid-abundant
      clones, pEMB4 and 94, were expressed very early during culture, suggesting that
      these genes are associated with development and are not simply expressed as a
      consequence of differentiation. The accumulation patterns of five cloned mRNAs
      may indicate the activation of specific genes associated with the major
      morphological and physiological activities connected with the differentiation of
      embryoids in vitro. These results suggest that embryoid-abundant gene expression
      is causally related to this pathway because gene expression is spatially and
      temporally specific and is not observed when microspores are cultured under
      noninductive conditions.

PMID- 16653193
TI  - Isolation and characterization of two safflower oleoyl-acyl carrier protein
      thioesterase cDNA clones.
AB  - Oleoyl-acyl carrier protein (18:1-ACP) thioesterase has been partially purified
      from developing safflower (Carthamus tinctorius) seeds. Protein species with
      molecular masses of 34 and 40 kD associated with thioesterase activity were
      identified and partially sequenced. Analysis of amino-terminal and internal
      cyanogen bromide peptide sequences revealed no differences in the primary
      structure of the two species. Amino acid sequence was used to design degenerate
      oligonucleotides for primers in a polymerase chain reaction (PCR) using safflower
      embryo cDNA as a template. A 380-base pair PCR product was used to isolate two
      classes of cDNA clones, designated 2-1 and 5-2, from the embryo cDNA library.
      Clone 2-1 encodes a 389-amino acid protein including a 60-amino acid transit
      peptide, and contains all of the protein sequence determined from the 34- and 40
      kD proteins. Clone 5-2 encodes a 385-amino acid protein with 80% identity to that
      encoded by 2-1. Expression of the two safflower cDNA clones in Escherichia coli
      resulted in a 50- to 100-fold increase in the level of 18:1-ACP thioesterase
      activity. Both thioesterases are most active on 18:1-ACP; however, the enzyme
      encoded by 5-2 shows less discrimination against saturated 16- and 18-carbon acyl
      ACP substrates.

PMID- 16653194
TI  - Exogenous Ethylene Inhibits Nodulation of Pisum sativum L. cv Sparkle.
AB  - Exogenous ethylene inhibited nodulation on the primary and lateral roots of pea,
      Pisum sativum L. cv Sparkle. Ethylene was more inhibitory to nodule formation
      than to root growth; nodule number was reduced by half with only 0.07 muL/L
      ethylene applied continually to the roots for 3 weeks. The inhibition was
      overcome by treating roots with 1 mum Ag(+), an inhibitor of ethylene action.
      Exogenous ethylene also inhibited nodulation on sweet clover (Melilotus alba) and
      on pea mutants that are hypernodulating or have ineffective nodules. Exogenous
      ethylene did not decrease the number of infections per centimeter of lateral pea
      root, but nearly all of the infections were blocked when the infection thread was
      in the basal epidermal cell or in the outer cortical cells.

PMID- 16653195
TI  - Structure and Expression of a Heat-Shock Protein 83 Gene of Pharbitis nil.
AB  - Four cDNA clones representing mRNAs whose levels were affected by a photoperiod
      that induces flowering in Pharbitis nil were isolated by a differential
      hybridization screening procedure. The level of mRNAs represented by three clones
      (12L, 15L, and 17L) increased following a photoperiod that induces flowering and
      that represented by the fourth clone (clone 27) increased under conditions in
      which flowering was inhibited. DNA sequence analysis showed that one cDNA, clone
      17L, is homologous to members of the 83- to 90-kD heat-shock protein (hsp) gene
      family. The corresponding gene, hsp83A, was isolated and its DNA sequence was
      determined. hsp83A encodes a protein that exhibits 70% amino acid identity with
      Drosophila melanogaster HSP83. The P. nil hsp83A gene contains two introns within
      the coding region. hsp83A mRNA was not detectable in cotyledons of plants grown
      in continuous light, but its level increased transiently following a 14-h dark
      period and reached a maximum 2 h after the lights were turned on. A dramatic
      increase in the level of hsp83A mRNA was also found 2 h after an end-of-day dark
      treatment. Genomic Southern blot analysis demonstrated that the P. nil hsp83-90
      gene family consists of at least six members, one of which appears to be
      constitutively expressed in the light.

PMID- 16653196
TI  - Structure and Light-Induced Expression of a Small Heat-Shock Protein Gene of
      Pharbitis nil.
AB  - To isolate genes that are regulated by a photoperiod that promotes flowering in
      Pharbitis nil, a cDNA library representing mRNA of induced cotyledons was
      screened by differential hybridization. The DNA sequence of one cDNA clone
      isolated by this approach, clone 12L, showed homology to plant small heat-shock
      protein (hsp) genes. P. nil genomic clones hybridizing to clone 12L were
      isolated, and the DNA sequences of two P. nil small hsp (shsp) genes, shsp-1 and
      shsp-2, were determined. The derived amino acid sequences of shsp-1 and shsp-2
      showed maximum homology to the 17.9-kD soybean hsp, a member of the class II
      cytoplasmic hsps found in plants. A study of the expression of shsp-1 and shsp-2
      genes by RNase protection assay indicated that shsp-1 is induced by photoperiod,
      by light treatment of dark-grown P. nil seedlings, and by heat shock, and that
      shsp-2 is induced only by heat shock. Analysis of the sequences of the
      nontranscribed region indicates that both genes contain multiple heat-shock
      elements. The shsp-1 gene, in addition, contains sequences homologous to the GT-1
      binding site, which may play a role in its light-regulated expression.

PMID- 16653197
TI  - The effect of heat shock on morphogenesis in barley : coordinated circadian
      regulation of mRNA levels for light-regulated genes and of the capacity for
      accumulation of chlorophyll protein complexes.
AB  - The effect of daily heat-shock treatments on gene expression and morphogenesis of
      etiolated barley (Hordeum vulgare) was investigated. Heat-shock treatments in the
      dark induced shortening of the primary leaves and the coleoptiles to the length
      of those in light-grown plantlets. In addition, the mRNA levels of the light
      induced genes that were investigated were raised under these conditions and
      showed distinct oscillations over a period of at least 3 d. While the mRNA levels
      for chlorophyll a/b binding protein (LHC II), plastocyanin, and the small subunit
      of ribulose-1,5-bisphosphate carboxylase had maxima between 8 and 12 pm (12-16h
      after the last heat-shock treatment), the mRNA levels for thionin oscillated with
      a phase opposed to that of LHC II. Etiolated barley, the circadian oscillator of
      which was synchronized by cyclic heatshock treatments, was illuminated for a
      constant interval at different times of the day; this led to the finding that
      greening was fastest at the time when the maximal levels of mRNA for LHC II were
      also observed. Whereas accumulation of chlorophyll a during a 4-h period of
      illumination oscillated by a factor of 3, chlorophyll b accumulation changed 10-
      to 15-fold. Similarly, accumulation of LHC II was highest when pigments
      accumulated maximally. Hence, greening or, in other words, thylakoid membrane
      assembly is under control of the circadian oscillator.

PMID- 16653198
TI  - Tonoplast-bound protein kinase phosphorylates tonoplast intrinsic protein.
AB  - Tonoplast intrinsic protein (TIP) is a member of a family of putative membrane
      channels found in bacteria, animals, and plants. Plants have seed-specific,
      vegetative/reproductive organ-specific, and water-stress-induced forms of TIP.
      Here, we report that the seed-specific TIP is a phosphoprotein whose
      phosphorylation can be monitored in vivo by allowing bean cotyledons to take up
      [(32)P]orthophosphate and in vitro by incubating purified tonoplasts with gamma
      labeled [(32)P]ATP. Characterization of the in vitro phosphorylation of TIP
      indicates that a membrane-bound protein kinase phosphorylates TIP in a Ca(2+)
      dependent manner. The capacity of the isolated tonoplast membranes to
      phosphorylate TIP declined markedly during seed germination, and this decline
      occurred well before the development-mediated decrease in TIP occurs.
      Phosphoamino acid analysis of purified, radiolabeled TIP showed that serine is
      the major, if not only, phosphorylated residue, and cyanogen bromide cleavage
      yielded a single radioactive peptide peak on a reverse-phase high-performance
      liquid chromatogram. Estimation of the molecular mass of the cyanogen bromide
      phosphopeptide by laser desorption mass spectroscopy led to its identification as
      the hydrophilic N-terminal domain of TIP. The putative phosphate-accepting serine
      residue occurs in a consensus phosphorylation site for serine/threonine protein
      kinases.

PMID- 16653199
TI  - The aba Mutant of Arabidopsis thaliana (L.) Heynh. Has Reduced Chlorophyll
      Fluorescence Yields and Reduced Thylakoid Stacking.
AB  - It has been shown that the aba mutant of Arabidopsis thaliana (L.) Heynh. is
      impaired in epoxy-carotenoid biosynthesis and accumulates the epoxy-carotenoid
      precursor, zeaxanthin (C.D. Rock, J.A.D. Zeevaart [1991] Proc Natl Acad Sci USA
      88: 7496-7499). In addition to providing conclusive evidence for the indirect
      pathway of abscisic acid biosynthesis from epoxy-carotenoids, the aba mutation
      offers a powerful means to study the function of xanthophylls (oxygenated
      carotenoids) in photosynthesis. We measured in vivo the chlorophyll (Chl)
      fluorescence parameters F(o) (initial), F(m) (maximum), F(v) (variable = F(m) -
      F(o)), and t((1/2)) (half-rise time of fluorescence induction) of wild-type (WT)
      and three allelic aba mutants. The mutant genotypes had significantly lower F(o)
      and F(m) values relative to those of WT. The F(v)/F(m) ratio and t((1/2)), which
      are parameters affected by photochemical efficiency, photosystem II (PSII), and
      plastoquinone pool sizes, were similar in the aba alleles and WT. Because the aba
      genotypes accumulate high levels of zeaxanthin, which is involved in
      nonphotochemical quenching of Chl fluorescence, we propose that the reduced
      fluorescence yields in the aba genotypes are a consequence of the accumulated
      zeaxanthin. Measurement of PSII oxygen evolution rates in isolated thylakoid
      membranes of WT and aba-4 confirmed that quantum efficiency was not altered in
      aba-4 but indicated that the mutant had reduced PSII activity in vitro. Electron
      microscopy revealed an abnormal chloroplast ultrastructure in the aba plants: the
      mutants had significantly fewer thylakoid lamellae per granum stack but
      significantly more grana per chloroplast, as well as more chloroplasts per cell
      than WT. Immunoblot analysis established that aba-4 had normal levels of the Chl
      a/b-binding core polypeptide of PSII (CP29) and the PSII light-harvesting Chl a/b
      binding complex. These results provide evidence for the role of zeaxanthin in
      nonphotochemical fluorescence quenching and suggest involvement of epoxy
      carotenoids and/or zeaxanthin in thylakoid stacking and PSII activity.

PMID- 16653200
TI  - Purification and partial characterization of a membrane-associated lipoxygenase
      in tomato fruit.
AB  - Membrane-associated lipoxygenase from green tomato (Lycopersicon esculentum L. cv
      Caruso) fruit has been purified 49-fold to a specific activity of 8.3 mumol.min(
      1).mg(-1) of protein by solubilization of microsomal membranes with Triton X-100,
      followed by anion- exchange and size-exclusion chromatography. The apparent
      molecular mass of the enzyme was estimated to be 97 and 102 kD by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and size-exclusion chromatography,
      respectively. The purified membrane lipoxygenase preparation consisted of a
      single major band following sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, which cross-reacts with immunoserum raised against soluble
      soybean lipoxygenase 1. It has a pH optimum of 6.5, an apparent K(m) of 6.2 mum,
      and V(max) of 103. mumol.min(-1).mg(-1) of protein with linoleic acid as
      substrate. Corresponding values for the partially purified soluble lipoxygenase
      from tomato are 3.8 mum and 1.3 mumol.min(-1).mg(-1) of protein, respectively.
      Thus, the membrane-associated enzyme is kinetically distinguishable from its
      soluble counterpart. Sucrose density gradient fractionation of the isolated
      membranes indicated that the membrane-associated lipoxygenase sediments with
      thylakoids. A lipoxygenase band with a corresponding apparent mol wt of 97,000
      was identified immunologically in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis-resolved proteins of purified thylakoids prepared from intact
      chloroplasts isolated from tomato leaves and fruit.

PMID- 16653201
TI  - Dynamics of Nitrogenous Assimilate Partitioning between Cytoplasmic and Vacuolar
      Fractions in Carrot Cell Suspension Cultures.
AB  - Bulk vacuole isolation, gas chromatography-mass spectrometry,, and high
      performance liquid chromatography have been used to investigate the accumulation
      and partitioning of assimilated nitrogen supplied as (15)NH(4)Cl between vacuolar
      and extravacuolar (cytoplasmic) fractions of protoplasts from suspension cultures
      of carrot (Daucus carota L. cv Chantenay). Glutamine was the most abundant amino
      acid in the vacuole of protoplasts from late-exponential phase cells, whereas
      alanine, glutamate, and gamma-aminobutyric acid were located primarily in the
      cytoplasmic fraction. In (15)N-feeding studies, newly synthesized glutamine
      partitioned strongly to the vacuole, whereas glutamate partitioned strongly to
      the cytoplasm, gamma-aminobutyric acid was totally excluded from the vacuole, and
      alanine was distributed in both compartments. Comparison of the (15)N-enrichment
      patterns suggests that initial assimilation to glutamine occurs within a
      subcompartment of the cytoplasmic fraction. The protoplast-feeding technique may
      be extended to investigate cytoplasmic compartmentation further.

PMID- 16653202
TI  - Physiological Aspects of Sugar Exchange between the Gametophyte and the
      Sporophyte of Polytrichum formosum.
AB  - The sporophyte of bryophytes is dependent on the gametophyte for its carbon
      nutrition. This is especially true of the sporophytes of Polytrichum species, and
      it was generally thought that sucrose was the main form of sugar for long
      distance transport in the leptom. In Polytrichum formosum, sucrose was the main
      soluble sugar of the sporophyte and gametophyte tissues, and the highest
      concentration (about 230 mm) was found in the haustorium. In contrast, sugars
      collected from the vaginula apoplast were mainly hexoses, with traces of sucrose
      and trehalose. p-Chloromercuribenzene sulfonate, a nonpermeant inhibitor of the
      cell wall invertase, strongly reduced the hexose to sucrose ratio. The highest
      cell wall invertase activity (pH 4.5) was located in the vaginula, whereas the
      highest activity of a soluble invertase (pH 7.0) was found in both the vaginula
      and the haustorium. Glucose uptake was carrier-mediated but only weakly dependent
      on the external pH and the transmembrane electrical gradient, in contrast to
      amino acid uptake (S. Renault, C. Despeghel-Caussin, J.L. Bonnemain, S. Delrot
      [1989] Plant Physiol 90: 913-920). Furthermore, addition of 5 or 50 mm glucose to
      the incubation medium induced a marginal depolarization of the transmembrane
      potential difference of the transfer cells and had no effect on the pH of this
      medium. Glucose was converted to sucrose after its absorption into the
      haustorium. These results demonstrate the noncontinuity of sucrose at the
      gametophyte/sporophyte interface. They suggest that its conversion to glucose and
      fructose at this interface, and the subsequent reconversion to sucrose after
      hexose absorption by haustorium cells, mainly governs sugar accumulation in this
      latter organ.

PMID- 16653203
TI  - Identification of Endogenous Gibberellins in Dormant Bulbils of Chinese Yam,
      Dioscorea opposita.
AB  - It is known that dormancy of the genus Dioscorea is induced by application of
      gibberellin (GA) A(3). To understand the role of GAs in dormancy induction,
      endogenous GAs have been identified by Kovats retention indices and full mass
      spectra from capillary gas chromatography-mass spectrometry analysis of purified
      extract from dormant bulbils of Dioscorea opposita Thunb. These include GA(4),
      GA(9), GA(12), GA(19), GA(20), GA(24), GA(36), and GA(53); their presence
      suggests the occurrence of two biosynthetic pathways in D. opposita bulbils, the
      early 13-hydroxylation pathway and the non-13-hydroxylation pathway.

PMID- 16653204
TI  - Role of the Leader Sequence during Thermal Repression of Translation in Maize,
      Tobacco, and Carrot Protoplasts.
AB  - The 5'-untranslated leader of maize (Zea mays) heat-shock protein (hsp) 70 mRNA
      is required for translational competence during heat shock in protoplasts. When
      the beta-glucuronidase gene was used as a reporter mRNA, expression at elevated
      temperatures increased more than 10-fold when the hsp70 leader constituted the 5'
      untranslated region. The hsp70 leader did not affect the physical half-life of
      the mRNA and, therefore, does not function at the level of transcript stability.
      The maize hsp70 leader was required to escape thermal repression in both maize
      and tobacco (Nicotiana tabacum) but was less effective in carrot. In addition,
      mRNAs containing the tobacco mosaic virus untranslated leader (omega) were also
      efficiently translated during heat shock, data suggesting that the presence of
      the omega sequence enables the transcript to escape the translational repression
      that occurs during thermal stress.

PMID- 16653205
TI  - Dormancy of the barley grain is correlated with gibberellic Acid responsiveness
      of the isolated aleurone layer.
AB  - The relationship between barley grain dormancy and gibberellic acid (GA(3))
      responsiveness of aleurone layers has been investigated. Barley (Hordeum
      distichum L. cvs Triumph and Kristina) grains were matured under defined
      conditions in a phytotron. Grains of Triumph plants grown under long-day/warm
      conditions had lower dormancy levels than grains of plants grown under short
      day/cool conditions. Aleurone layers isolated from grains of long-day Triumph
      plants secreted more alpha-amylase and had a higher responsiveness to GA(3) as
      measured by alpha-amylase secretion. Storage of the grains increased both the
      percentage of germination and the responsiveness of the aleurone to GA(3). Use of
      different sterilization methods to break dormancy confirmed the correlation
      between germination percentage and aleurone layer GA(3) responsiveness. The
      response of embryoless Triumph grains to GA(3) was lower than that of the
      isolated aleurone layers, suggesting a role of the starchy endosperm in
      regulating the GA(3) response of the aleurone layer. Grains of the cultivar
      Kristina harvested from short day- and long day-grown plants lacked dormancy, and
      their isolated aleurone layers had a similar responsiveness to GA(3) as measured
      by alpha-amylase secretion. The data indicate that the physiological state of the
      aleurone layers contributes to the percentage germination of the grains.

PMID- 16653206
TI  - Diurnal and Circadian Light-Harvesting Complex and Quinone B-Binding Protein
      Synthesis in Leaves of Tomato (Lycopersicon esculentum).
AB  - In leaves of tomato (Lycopersicon esculentum), the synthesis of a light
      harvesting complex (LHC) polypeptide of photosystem II and the quinone B (Q(B))
      binding protein varies at different time points during the day. In vivo labeling
      with [(35)S]methionine revealed diurnal oscillations of synthesis of these
      thylakoid membrane proteins. Both proteins are synthesized at elevated levels
      right after the transition from darkness to light, a maximum is reached around
      noon, and decreasing levels were measured during the afternoon and night. In
      addition, in constant darkness both proteins were also synthesized to varied
      extents at different diurnal time points. Together, these results indicate that
      the synthesis of a LHC II and the Q(B)-binding protein is under the control of
      the circadian clock. This circadian oscillation of LHC II protein synthesis
      correlates with the very well documented circadian Lhc a/b mRNA accumulation.

PMID- 16653207
TI  - Coordinate regulation of cytochrome and alternative pathway respiration in
      tobacco.
AB  - In suspension cells of NT1 tobacco (Nicotiana tabacum L. cv bright yellow),
      inhibition of the cytochrome pathway of respiration with antimycin A induced a
      large increase in the capacity of the alternative pathway over a period of
      approximately 12 h, as confirmed in both whole cells and isolated mitochondria.
      The increase in alternative pathway capacity required de novo RNA and protein
      synthesis and correlated closely with the increase of a 35-kD alternative oxidase
      protein. When the cytochrome pathway of intact cells was inhibited by antimycin
      A, respiration proceeded exclusively through the alternative pathway, reached
      rates significantly higher than before antimycin A addition, and was not
      stimulated by p-trifluoromethoxycarbonylcyanide (FCCP). When inhibition of the
      cytochrome pathway was relieved, alternative pathway capacity and the level of
      the 35-kD alternative oxidase protein declined. Respiration rate also declined
      and could once again be stimulated by FCCP. These observations show that the
      capacities of the mitochondrial electron transport pathways can be regulated in a
      coordinate fashion.

PMID- 16653208
TI  - Rapid Changes in Cell Wall Yielding of Elongating Begonia argenteo-guttata L.
      Leaves in Response to Changes in Plant Water Status.
AB  - Elongation and epidermal cell turgor (P) of Begonia argenteoguttata L. leaves
      were simultaneously measured to determine the wall-yielding behavior of growing
      leaf cells in response to changes in plant water status. Rapid changes in plant
      water status were imposed by irrigating the rooting media with solutions of -0.20
      and -0.30 MPa mannitol. These treatments caused decreases in P of 0.09 and 0.17
      MPa, respectively. The decreases in P were complete within 10 min, and P did not
      change thereafter. Following treatments, leaf elongation was nil for periods of
      25 to 38 min. Subsequently, elongation recovered to steady rates that were 45 or
      75% lower than in the well-watered controls. Leaves of plants that were
      pretreated with -0.30 MPa of mannitol and rewatered showed an increase in P of
      0.19 MPa, which was complete within 15 min; P did not change thereafter.
      Rewatering caused a several-fold increase in leaf elongation rates, which
      subsequently declined while P was increasing, to reach steady rates similar to
      that of the controls. Several estimates of elastic deformation indicated that
      most of the elongation responses to altered P were due to changes in irreversible
      deformation. The results showed that the initial effects of changes in P on leaf
      elongation were partially compensated for by changes in the cell wall-yielding
      properties. We conclude that linear relationships between P and adjusted growth
      rates are not necessarily indicative of constant wall-yielding properties.
      Instead, these relationships may reflect the effect of P on wall-loosening
      processes.

PMID- 16653209
TI  - Species-dependent variation in the interaction of substrate-bound ribulose-1,5
      bisphosphate carboxylase/oxygenase (rubisco) and rubisco activase.
AB  - Purified spinach (Spinacea oleracea L.) and barley (Hordeum vulgare L.) ribulose
      1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase supported 50 to 100%
      activation of substrate-bound Rubisco from spinach, barley, wheat (Triticum
      aestivum L.), soybean (Glycine max L.), pea (Pisum sativum L.), Arabidopsis
      thaliana, maize (Zea mays L.), and Chlamydomonas reinhardtii but supported only
      10 to 35% activation of Rubisco from three Solanaceae species, tobacco (Nicotiana
      tabacum L.), petunia (Petunia hybrida L.), and tomato (Lycopersicon esculentum
      L.). Conversely, purified tobacco and petunia Rubisco activase catalyzed 75 to
      100% activation of substrate-bound Rubisco from the three Solanacee species but
      only 10 to 25% activation of substrate-bound Rubisco from the other species.
      Thus, the interaction between substrate-bound Rubisco and Rubisco activase is
      species dependent. The species dependence observed is consistent with
      phylogenetic relationships previously derived from plant morphological
      characteristics and from nucleotide and amino acid sequence comparisons of the
      two Rubisco subunits. Species dependence in the Rubisco-Rubisco activase
      interaction and the absence of major anomalies in the deduced amino acid sequence
      of tobacco Rubisco activase compared to sequences in non-Solanaceae species
      suggest that Rubisco and Rubisco activase may have coevolved such that amino acid
      changes that have arisen by evolutionary divergence in one of these enzymes
      through spontaneous mutation or selection pressure have led to compensatory
      changes in the other enzyme.

PMID- 16653210
TI  - Reversible o(2) inhibition of nitrogenase activity in attached soybean nodules.
AB  - Various forms of stress result in decreased O(2) permeability or decreased
      capacity to consume O(2) in legume root nodules. These changes alter the nodule
      interior O(2) concentration (O(i)). To determine the relationship between O(i)
      and nitrogenase activity in attached soybean (Glycine max) nodules, we controlled
      O(i) by varying external pO(2) while monitoring internal H(2) concentration
      (H(i)) with microelectrodes. O(i) was monitored by noninvasive leghemoglobin
      spectrophotometry (nodule oximetry). After each step-change in O(i), H(i)
      approached a new steady state, with a time constant averaging 23 s. The rate of
      H(2) production by nitrogenase was calculated as the product of H(i), nodule
      surface area, and nodule H(2) permeability. H(2) permeability was estimated from
      O(2) permeability (measured by nodule oximetry) by assuming diffusion through air
      filled pores; support for this assumption is presented. O(i) was nearly optimal
      for nitrogenase activity (H(2) production) between 15 and 150 nm. A 1- to 2-min
      exposure to elevated external pO(2) (40-100 kPa) reduced H(i) to zero, but
      nitrogenase activity recovered quickly under air, often in <20 min. This rapid
      recovery contrasts with previous reports of much slower recovery with longer
      exposures to elevated pO(2). The mechanism of nitrogenase inhibition may differ
      between brief and prolonged O(2) exposures.

PMID- 16653211
TI  - Energy storage of linear and cyclic electron flows in photosynthesis.
AB  - The energy storage of photosynthesis in the green alga Chlorella vulgaris was
      determined by pulsed, time-resolved photoacoustics. The energy storage of the
      linear electron transfer process in photosynthesis, of cyclic photosystem (PS) I,
      and possibly of PSII was determined by selection of excitation wavelength and of
      flash interval. At 695 nm excitation, a rather large cyclic PSI energy storage of
      0.68 +/- 0.04 eV/quantum of energy at 8 ms after a 1-mus flash was obtained. This
      energy remained the same at flash intervals of 0.35 to 60 s and was independent
      of the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. We tentatively assign
      this energy to the ferredoxin-NADP-reductase-ferredoxin and oxidized cytochrome
      b(6)/f complexes. An efficient distribution of energy between cyclic and linear
      systems is obtained with the simple assumption that the turnover time of the
      cyclic system is slower than that of the linear system. The energy storage of
      linear electron flow was determined by 655 nm excitation of Chlorella with a
      short flash interval of 0.35 s per flash. It was calculated to be 0.50 +/- 0.03
      eV/hv, close to that expected for oxygen and NADPH formation. The energy storage
      of PSII is determined by excitation of Chlorella at 655 nm with a long flash
      interval of 60 s per flash. It was calculated to be 1.07 +/- 0.05 eV/hv,
      consistent with the energy storage being in S-states and the secondary electron
      acceptor of PSII with a calculated redox energy of 1.03 eV/hv. In the presence of
      1 mum 3-(3,4-dichlorophenyl)-1,1-dimethylurea, the calculated energy storage in
      PSII is still significant, 0.53 +/- 0.04 eV/hv. This probably indicates a
      significant cyclic electron flow around PSII. These cyclic flows may contribute
      considerably to energy storage in photosynthesis.

PMID- 16653212
TI  - Carbon fluxes in mature peach leaves.
AB  - The turnover and transport of sugars are described in peach (Prunus persica L.
      Batsch), a species exporting both sucrose and sorbitol. Apparent export rate was
      slower in peach leaves than in leaves of herbaceous species. Sorbitol was the
      major soluble end product of photosynthesis and the major soluble carbohydrate in
      the leaf (higher than sucrose). Carbon fluxes were described using (14)C
      labeling, radioactivity loss curves, and compartmental analysis during the second
      half of the photoperiod when chemical steady state was reached for soluble
      carbohydrates. The measured specific radioactivity of sucrose was typical of a
      primary product. The delayed decrease in specific radioactivity of sorbitol
      indicated that part of it was secondarily synthesized. Sucrose is proposed to be
      the carbon source for the delayed synthesis of sorbitol in the light. The
      sorbitol to sucrose ratio was higher in the petiole than in the leaf tissues. In
      phloem sap, obtained using stylectomy of aphids and collected from the main stem
      between source leaves and apex, this ratio was lower than in the petiole,
      suggesting a preferential sorbitol demand by sinks.

PMID- 16653213
TI  - Comparison of polyphenol oxidase expression in glandular trichomes of solanum and
      lycopersicon species.
AB  - Tetralobulate glandular trichomes are present on the foliage of many solanaceous
      species. Resistance of many of these species to insects is conditioned by the
      ability of trichomes to rupture upon contact and to rapidly polymerize their
      contents, resulting in entrapment of insects in hardened trichome exudate. In the
      wild potato, Solanum berthaultii, polymerization of trichome exudate is initiated
      by a soluble M(r) 59,000 polyphenol oxidase (PPO), which is a dominant protein
      constituent of the organ. PPOs, although ubiquitous in angiosperms, typically
      display great heterogeneity in molecular weight and are found at low levels in
      plant cells. Because of the unusually high accumulation and tissue-specific
      expression of the M(r) 59,000 PPO in S. berthaultii glandular trichomes, we
      analyzed trichome proteins of a number of Lycopersicon and Solanum species to
      assess the extent to which possession of the M(r) 59,000 PPO is conserved.
      Trichomes were collected manually and examined for PPO activity, immuno-cross
      reactivity with S. berthaultiiM(r) 59,000 PPO, and protein content. In addition,
      N-terminal amino acid sequences were obtained for five trichome PPOs. All species
      analyzed possessed trichome PPOs similar in structure and level of expression to
      that of S. berthaultii. The relationship between sequences and structures of
      these conserved PPOs and the variable PPOs of leaf is discussed.

PMID- 16653214
TI  - Effects of glucose starvation on mitochondrial subpopulations in the meristematic
      and submeristematic regions of maize root.
AB  - Mitochondria isolated from 3-mm long maize (Zea mays L. var Dea) root tips were
      found to be heterogeneous on Percoll density gradients. The ultrastructure of
      these isolated mitochondria correlated well with that of mitochondria observed in
      situ and was consistent with the existence of mitochondria at different stages of
      maturation during cell development. The mitochondria of higher density presented
      an ultrastructure with many cristae and a dense matrix. These mitochondria showed
      classic respiratory properties, although with low ADP/O ratios. In contrast, the
      mitochondria of lower density showed few cristae and a clear matrix and did not
      seem to be fully functional because their rate of respiration was low and showed
      weak respiratory control. Lower- and higher- density mitochondria were shown to
      be differentially affected during the first stages of glucose starvation. The
      higher-density mitochondria from glucose-starved maize root tips retained the
      ultrastructure and most of the respiratory properties of nonstarved mitochondria,
      whereas lower- and intermediate-density mitochondria were absent in the
      mitochondrial preparations from glucose-starved maize root tips and were not
      observed in situ. Quantitatively, there was a decrease of the total mitochondrial
      pool when expressed as the amount of mitochondrial protein per root tip. However,
      this decrease affected low- and intermediate-density mitochondria, but not higher
      density mitochondria. Thus, it was shown that a significant pool of functional
      mitochondria is maintained in maize root tips during the first stages of glucose
      starvation. The reasons for these apparently selective effects of glucose
      starvation on mitochondria are discussed in relation to effects on mitotic and
      differentiation processes.

PMID- 16653215
TI  - Phenotypic Analysis of a Dwarf Wheat (Triticum aestivum L.) with Altered
      Phytochrome-Mediated Growth Responses.
AB  - The influence of the amount of red light relative to far red light (red/far red
      ratio) on leaf-sheath elongation, leaf length, tillering, assimilate partitioning
      to shoots and roots, and chlorophyll content in a dwarf wheat (Triticum aestivum
      L. cv Tibet Dwarf) and seven other dwarf and standard cultivars was determined.
      All cultivars tested showed far red-stimulated leaf and leaf-sheath elongation
      except Tibet Dwarf. Tibet Dwarf was also unresponsive to a brief end-of-day
      exposure to far red light, although the other cultivars exhibited increased leaf
      sheath and leaf length. In these cultivars, the effects of an end-of-day 5-min
      far red exposure were reversible by a subsequent 5-min red light exposure.
      Shoot/root ratios were higher and tillering was suppressed by increased far red
      irradiance in all cultivars except Tibet Dwarf. In addition, Tibet Dwarf was less
      responsive to dark-induced leaf and leaf-sheath elongation (etiolation) and
      retained chlorophyll in dark-adapted leaves longer than control cultivars. Tibet
      Dwarf did not differ from the other cultivars in leaf chlorophyll content.
      Western blot analysis, using an antibody against phytochrome A, showed that dark
      grown Tibet Dwarf shoots contained at least twice the amount of detectable
      phytochrome A protein present in the other wheat cultivars. These results, plus
      the short, thick-stemmed, dark-pigmented phenotype of Tibet Dwarf suggest the
      possibility of a mutation in the phytochrome/signal transduction pathway.

PMID- 16653216
TI  - Resistance to Acetolactate Synthase-Inhibiting Herbicides in Annual Ryegrass
      (Lolium rigidum) Involves at Least Two Mechanisms.
AB  - WLR1, a biotype of Lolium rigidum Gaud. that had been treated with the
      sulfonylurea herbicide chlorsulfuron in 7 consecutive years, was found to be
      resistant to both the wheat-selective and the nonselective sulfonylurea and
      imidazolinone herbicides. Biotype SLR31, which became cross-resistant to
      chlorsulfuron following treatment with the aryloxyphenoxypropionate herbicide
      diclofop-methyl, was resistant to the wheat-selective, but not the nonselective,
      sulfonylurea and imidazolinone herbicides. The concentrations of herbicide
      required to reduce in vitro acetolactate synthase (ALs) activity 50% with respect
      to control assays minus herbicide for biotype WLR1 was greater than those for
      susceptible biotype VLR1 by a factor of >30, >30, 7,4, and 2 for the herbicides
      chlorsulfuron, sulfometuron-methyl, imazapyr, imazathapyr, and imazamethabenz,
      respectively. ALS activity from biotype SLR31 responded in a similar manner to
      that of the susceptible biotype VLR1. The resistant biotypes metabolized
      chlorsulfuron more rapidly than the susceptible biotype. Metabolism of 50% of
      [phenyl-U-(14)C]chlorsulfuron in the culms of two-leaf seedlings required 3.7 h
      in biotype SLR31, 5.1 h in biotype WLR1, and 7.1 h in biotype VLR1. In all
      biotypes the metabolism of chlorsulfuron in the culms was more rapid than that in
      the leaf lamina. Resistance to ALS inhibitors in L. rigidum may involve at least
      two mechanisms, increased metabolism of the herbicide and/or a herbicide
      insensitive ALS.

PMID- 16653217
TI  - Short-term experiments on ion transport by seedlings and excised roots :
      technique and validity.
AB  - The absorption of K(+) by excised roots of barley (Hordeum vulgare L. cv
      California Mariout) has been systematically compared with that of entire,
      undisturbed seedlings. Some experiments have also been done with wheat (Triticum
      aestivum L.) and an amphiploid obtained from a cross between it and salt-tolerant
      tall wheatgrass (Lophopyrum elongatum Host Love [syn. Agropyron elongatum Host]).
      For all three genotypes, the rate of K(+) absorption measured in a 20-min period
      was identical for entire 8-d-old seedlings and their excised roots within the
      experimental error. Manipulation gentler than root excision, viz. careful
      transfer of seedlings from one experimental solution to another, was also without
      effect on the rate of K(+) absorption. Absorption of K(+) measured by assay of
      its (86)Rb label in the tissue was identical with that measured by K(+) depletion
      of the experimental solutions assayed chemically. For the plant materials and
      conditions of these experiments, the excised root technique for studying ion
      transport into roots is validated. The advantages of the technique, and findings
      differing from the present ones, are discussed.

PMID- 16653218
TI  - Salicylic Acid induces cyanide-resistant respiration in tobacco cell-suspension
      cultures.
AB  - Cyanide-resistant, alternative respiration in Nicotiana tabacum L. cv Xanthi-nc
      was analyzed in liquid suspension cultures using O(2) uptake and calorimetric
      measurements. In young cultures (4-8 d after transfer), cyanide inhibited O(2)
      uptake by up to 40% as compared to controls. Application of 20 mum salicylic acid
      (SA) to young cells increased cyanide-resistant O(2) uptake within 2 h.
      Development of KCN resistance did not affect total O(2) uptake, but was
      accompanied by a 60% increase in the rate of heat evolution from cells as
      measured by calorimetry. This stimulation of heat evolution by SA was not
      significantly affected by 1 mm cyanide, but was reduced by 10 mm
      salicylhydroxamic acid (SHAM), an inhibitor of cyanide-resistant respiration.
      Treatment of SA-induced or uninduced cells with a combination of cyanide and SHAM
      blocked most of the O(2) consumption and heat evolution. Fifty percent of the
      applied SA was taken up within 10 min, with most of the intracellular SA
      metabolized in 2 h. 2,6-Dihydroxybenzoic and 4-hydroxybenzoic acids also induced
      cyanide-resistant respiration. These data indicate that in tobacco cell
      suspension culture, SA induces the activity and the capacity of cyanide-resistant
      respiration without affecting the capacity of the cytochrome c respiration
      pathway.

PMID- 16653219
TI  - Inhibition and Ultraviolet-Induced Chemical Modification of UDP-Glucose:(1,3)
      beta-Glucan (Callose) Synthase by Chlorpromazine : Mechanism of Chlorpromazine
      Binding to the Plant Plasma Membrane.
AB  - UDP-glucose:(1,3)-beta-glucan (callose) synthase (CS) from storage tissue of red
      beet (Beta vulgaris L.) was strongly inhibited by the phenothiazine drug
      chlorpromazine (CPZ). In the absence of ultraviolet irradiation, CPZ was a
      noncompetitive inhibitor with 50% inhibitory concentration values for plasma
      membrane and solubilized CS of 100 and 90 mum, respectively. Both the Ca(2+)- and
      Mg(2+)- stimulated components of CS activity were affected. CPZ inhibition was
      partially alleviated at saturating levels of Ca(2+), but not Mg(2+), suggesting
      that CPZ interferes with the Ca(2+)-binding site of CS. Binding experiments with
      [(14)C]CPZ, however, showed strong non-specific partitioning of CPZ into the
      plasma membrane, providing evidence that perturbation of the membrane environment
      is probably the predominant mode of inhibition. Ultraviolet irradiation at 254 nm
      markedly enhanced CPZ inhibition, with complete activity loss following exposure
      to 4 mum CPZ for 2 min. Inhibition followed a pseudo-first order mechanism with
      at least three CPZ binding sites per CS complex. Under these conditions,
      [(3)H]CPZ was covalently incorporated into plasma membrane preparations by a free
      radical mechanism; however, polypeptide labeling profiles showed labeling to be
      largely nonspecific, with many polypeptides labeled even at [(3)H]CPZ levels as
      low as 1 mum, and with boiled membranes. Although CPZ is one of the most potent
      known inhibitors of CS, its use as a photolabel will require a homogeneous CS
      complex or establishment of conditions that protect against the interaction of
      CPZ with specific binding sites located on various polypeptide components of the
      CS complex.

PMID- 16653220
TI  - Photocontrol of the Accumulation of Plastid Polypeptides during Greening of
      Tomato Cotyledons : Potentiation by a Pulse of Red Light.
AB  - A pulse of red light acting through phytochrome accelerates the formation of
      chlorophyll upon subsequent transfer of dark-grown seedlings to continuous white
      light. Specific antibodies were used to follow the accumulation of representative
      subunits of the major photosynthetic complexes during greening of seedlings of
      tomato (Lycopersicon esculentum). The time course for accumulation of the various
      subunits was compared in seedlings that received a red light pulse 4 h prior to
      transfer to continuous white light and parallel controls that did not receive a
      red light pulse. The light-harvesting chlorophyll-binding proteins of photosystem
      II (LHC II), the 33-kD extrinsic polypeptide of the oxygen-evolving complex
      (OEC1), and subunit II of photosystem I (psaD gene product) all increased in the
      light, and did so much faster in seedlings that received the inductive red light
      pulse. The red light pulse had no significant effect on the abundance of the
      small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), nor
      on several plastid-encoded polypeptides: the large subunit of Rubisco, the beta
      subunit of the CF(1) complex of plastid ATPase, and the 43- and 47-kD subunits of
      photosystem II (CP43, CP47). Subunits I (cytochrome b(6)f) and III (Rieske Fe-S
      protein) of the cytochrome b(6)f complex showed a small or no increase as a
      result of the red pulse. The potentiation of greening by a pulse of red light,
      therefore, is not expressed uniformly in the abundance of all the photosynthetic
      complexes and their subunits.

PMID- 16653221
TI  - Fourier transform infrared microspectroscopy is a new way to look at plant cell
      walls.
AB  - Highly reproducible Fourier transform infrared (FTIR) spectra from both single
      onion (Allium cepa) cell walls and their constituent polymers were obtained under
      a variety of sampling conditions. The specificity of the chemical extraction
      sequence used in the preparation of the material was confirmed: pectins only are
      extracted by cyclohexanediaminetetraacetic acid and sodium carbonate, whereas
      xyloglucans are extracted by increasing concentrations of potassium hydroxide.
      There was very little contamination of the first potassium hydroxide extract with
      residual pectin. The low abundance of both phenolics and protein was also
      confirmed. The first sodium carbonate extraction almost completely removes esters
      remaining in the cell wall. We have demonstrated that FTIR spectroscopy can
      detect large conformational changes in pectic polymers on removal from the cell
      wall and on drying. FTIR spectroscopy provides a powerful and rapid assay for
      wall components and putative cross-links by identifying polymers and functional
      groups nondestructively in muro. The availability of micro-sampling and data
      acquisition techniques that permit subtraction of the blanket absorption of water
      make FTIR spectroscopy particularly suitable for studies of cell wall
      architecture. The use of polarizers with the microscope accessory permits
      determination of the orientation of particular functional groups with respect to
      the direction of cell elongation in carrot suspension cells.

PMID- 16653222
TI  - Photosystem II Core Phosphorylation Heterogeneity, Differential Herbicide
      Binding, and Regulation of Electron Transfer in Photosystem II Preparations from
      Spinach.
AB  - The effect of photosystem II core phosphorylation on the secondary quinone
      acceptor of photosystem II (Q(B)) domain environment was analyzed by comparative
      herbicide-binding studies with photosystem II preparations from spinach (Spinacia
      oleracea L.). It was found that phosphorylation reduces the binding affinity for
      most photosynthetic herbicides. The binding of synthetic quinones and of the
      electron acceptor 2,6-dichlorophenolindophenol is also reduced by photosystem II
      phosphorylation. Four photosystem II core populations isolated from membranes
      showed different extents of phosphorylation as well as different degrees of
      affinity for photosynthetic herbicides. These findings support the idea that
      heterogeneity of photosystem II observed in vivo could be, in part, due to
      phosphorylation.

PMID- 16653223
TI  - The Effect of 5OH-1,4-Naphthoquinone on Norway Spruce Seeds during Germination.
AB  - The effect of 5-OH-1,4-naphthoquinone (5OH-NQ), a known inhibitor of germination
      and growth and an inducer of oxidative stress, on seeds from Norway spruce (Picea
      abies) during germination was studied. 5OH-NQ was activated by homogenate from
      seeds to reactive species that reduce oxygen to superoxide radicals in vitro.
      Increasing concentrations of 5OH-NQ increased lipid peroxidation during this
      activation. Small effects of 5OH-NQ on germination of seeds were observed at
      concentrations up to 200 mum. However, higher concentrations, e.g. 500 and 1000
      mum, exerted more pronounced effects on seeds. These results suggest that the
      effect of 5OH-NQ was a delay rather than an inhibition of germination. However,
      the effect of 5OH-NQ on postgerminative growth was more potent than that on
      germination, and higher concentrations inhibited growth >97%. These results
      suggest that the seeds have a very effective defense system against quinone and
      reactive oxygen species, since the small effects of 5OH-NQ on germination and
      postgermination at concentrations up to 200 mum can be explained by the formation
      of a metabolite of 5OH-NQ that is not as reactive with oxygen as the original
      quinone. The 5OH-NQ metabolite collected during germination experiments showed
      differences in its absorption spectrum in comparison with 5OH-NQ, which suggest
      changes in structure. This metabolite was reduced by quinone reductase, but
      reduction of oxygen to superoxide radicals was not detected during its activation
      with homogenate from seeds. This metabolite may arise via a conjugation reaction,
      since the addition of 500 mum uridine 5'-diphosphoglucuronic acid or 3'
      phosphoadenosine-5'-phosphosulfate to the incubation mixture during activation of
      this metabolite by homogenate from seeds in vitro inhibited reduction of oxygen
      to superoxide radicals by 50 and 64%, respectively. The constitutive levels of
      superoxide dismutase and catalase were sufficient to prevent oxygen toxicity
      during activation of 5OH-NQ, since these enzymes were not induced when the seeds
      were treated with 200 mum 5OH-NQ.

PMID- 16653224
TI  - Effects of deuterium oxide on growth, proton extrusion, potassium influx, and in
      vitro plasma membrane activities in maize root segments.
AB  - Elongation of subapical segments of maize (Zea mays) roots was greatly inhibited
      by (2)H(2)O in the incubation medium. Short-term exposure (30 min) to (2)H(2)O
      slightly reduced O(2) uptake and significantly increased ATP levels. (2)H(2)O
      inhibited H(+) extrusion in the presence of both low (0.05 mm) and high (5 mm)
      external concentrations of K(+) (about 30 and 53%, respectively at 50% [v/v]
      (2)H(2)O). Experiments on plasma membrane vesicles showed that H(+)-pumping and
      ATPase activities were greatly inhibited by (2)H(2)O (about 35% at 50% [v/v]
      (2)H(2)O); NADH-ferricyanide reductase and 1,3-beta-glucan synthase activities
      were inhibited to a lesser extent (less than 15%). ATPase activities present in
      both the tonoplast-enriched and submitochondrial particle preparations were not
      affected by (2)H(2)O. Therefore, the effect of short incubation time and low
      concentration of (2)H(2)O is not due to a general action on overall cell
      metabolism but involves a specific inhibition of the plasma membrane H(+) 
      ATPase. K(+) uptake was inhibited by (2)H(2)O only when K(+) was present at a low
      (0.05 mm) external concentration where absorption is against its electrochemical
      potential. The transmembrane electric potential difference (E(m)) was slightly
      hyperpolarized by (2)H(2)O at low K(+), but was not affected at the higher K(+)
      concentrations. These results suggest a relationship between H(+) extrusion and
      K(+) uptake at low K(+) external concentration.

PMID- 16653225
TI  - Stimulation of growth and ion uptake in bean leaves by red and blue light.
AB  - Red and blue light both stimulate growth and ion accumulation in bean (Phaseolus
      vulgaris L.) leaves, and previous studies showed that the growth response is
      mediated by phytochrome and a blue-light receptor. Results of this study confirm
      that there is an additional photosynthetic contribution from the growing cells
      that supports ion uptake and growth. Disc expansion in the light was enhanced by
      exogenous K(+) and Rb(+), but was not specific for anions. Light increased K(+)
      accumulation and the rate of (86)Rb(+) uptake by discs, over darkness, with no
      effect of light quality. The photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1
      dimethylurea, inhibited light-driven (86)Rb(+) uptake by 75%. Light quality
      caused differences in short-term kinetics of growth and acidification of the leaf
      surface. At comparable fluence rates (50 mumol m(-2) s(-1)), continuous exposure
      to blue light increased the growth rate 3-fold after a 2-min lag, whereas red
      light caused a smaller growth response after a lag of 12 min. In contrast, the
      acidification of the leaf surface normally associated with growth was stimulated
      3-fold by red light but only slightly (1.3-fold) by blue light. This result shows
      that, in addition to acidification caused by red light, a second mechanism
      specifically stimulated by blue light is normally functioning in light-driven
      leaf growth.

PMID- 16653226
TI  - Expression of a Ripening-Related Avocado (Persea americana) Cytochrome P450 in
      Yeast.
AB  - One of the mRNAs that accumulates during the ripening of avocado (Persea
      americana Mill. cv Hass) has been previously identified as a cytochrome P450
      (P450) monooxygenase and the corresponding gene designated CYP71A1. In this
      report we demonstrate that during ripening the accumulation of antigenically
      detected CYP71A1 gene product (CYP71A1) correlates with increases in total P450
      and two P450-dependent enzyme activities: para-chloro-N-methylaniline
      demethylase, and trans-cinnamic acid hydroxylase (tCAH). To determine whether
      both of these activities are derived from CYP71A1, we have expressed this protein
      in yeast (Saccharomyces cerevisiae) using a galactose-inducible yeast promoter.
      Following induction, the microsomal fraction of transformed yeast cells undergoes
      a large increase in P450 level, attributable almost exclusively to the plant
      CYP71A1 protein. These membranes exhibit NADPH-dependent para-chloro-N
      methylaniline demethylase activity at a rate comparable to that in avocado
      microsomes but have no detectable tCAH. These results demonstrate both that the
      CYP71A1 protein is not a tCAH and that a plant P450 is fully functional upon
      heterologous expression in yeast. These findings also indicate that the
      heterologous P450 protein can interact with the yeast NADPH:P450 reductase to
      produce a functional complex.

PMID- 16653227
TI  - A Cyanobacterial Gene Encoding Peptidyl-Prolyl cis-trans Isomerase.
AB  - The rotA gene encoding peptidyl-prolyl cis-trans isomerase has been identified,
      sequenced, and shown to be transcribed in the cyanobacterium Synechococcus sp.
      PCC7942. Inactivation of the gene by replacement of a region containing the open
      reading frame with a gene conferring kanamycin resistance resulted in
      merodiploids containing both the wild type and the modified genomic region. We
      were not able to isolate a kanamycin-resistant mutant in which all the genomic
      wild-type copies were substituted, which suggests that such replacement could
      have been lethal.

PMID- 16653228
TI  - Phenotypic Complementation of High CO(2)-Requiring Mutants of the Cyanobacterium
      Synechococcus sp. Strain PCC 7942 by Inosine 5'-Monophosphate.
AB  - The high CO(2)-requiring mutants of Synechococcus PCC 7942, D4 and R14, were
      obtained by deletion or inactivation (respectively) of an open reading frame
      immediately downstream of rbc (the operon encoding the subunits of ribulose 1,5
      bisphosphate carboxylase/oxygenase). These mutants exhibit photosynthetic
      characteristics similar to those of high CO(2)-grown wild type, unlike other
      cyanobacterial high CO(2)-requiring mutants, where the apparent photosynthetic
      affinity for inorganic carbon is approximately 2 orders of magnitude lower than
      that of the wild type. Sequence analysis and metabolic complementation of the
      mutants by inosine 5'-monophosphate identified this open reading frame as the
      cyanobacterial equivalent of purK, the eubacterial gene encoding subunit II of
      phosphoribosyl aminoimidazole carboxylase in the purine biosynthetic pathway.
      Exposure of high CO(2)-grown Synechococcus to low CO(2) conditions led to the
      induction of transcription of purK. It is suggested that the high CO(2)-requiring
      phenotype of these mutants resulted from the defect in purine biosynthesis after
      exposure to low CO(2). We also raise the possibility that the level of cellular
      purines is involved in the process of adaptation of cyanobacteria to low
      concentrations of CO(2).

PMID- 16653229
TI  - Gibberellins and the Legume-Rhizobium Symbiosis : III. Quantification of
      Gibberellins from Stems and Nodules of Lima Bean and Cowpea.
AB  - Lima bean (Phaseolus lunatus L.) plants inoculated with Bradyrhizobium sp. strain
      127E14 displayed a period of marked internode elongation that was not observed in
      plants inoculated with other compatible bradyrhizobia, including strain 127E15.
      When strain 127E14 nodulated an alternate host, cowpea (Vigna unguiculata L.
      Walp), a similar, although less dramatic growth response induced by the bacteria
      was observed. It has been speculated that the elongative growth promotion brought
      about by inoculation with strain 127E14 is mediated by gibberellins (GAs). Using
      deuterated internal standards and gas chromatography-mass spectroscopy analysis,
      we have quantified the levels of GA(1), GA(20), GA(19), and GA(44) in nodules and
      stems of two varieties of lima bean (bush and pole) and one variety of cowpea
      that were inoculated with either strain 127E14 or 127E15. In nodules formed by
      strain 127E14 on lima bean, endogenous levels of GA(20) and GA(19) were 10 to 40
      times higher (35-88 ng/g dry weight) than amounts found in nodules formed by
      strain 127E15 (2.2-3.9 ng/g dry weight). Relative amounts of GA(44) were also
      higher (4- to 11-fold) in 127E14 nodules, but this increase was less pronounced.
      The rhizobial-induced increase of these GAs in the nodule occurred in both pole
      and bush varieties and seemed to be independent of host morphology. Regardless of
      rhizobial inoculum, levels of the "bioactive" GA(1) in the nodule (0.3-1.1 ng/g
      dry weight) were similar. In cowpea nodules, a similar, although smaller,
      difference in GA content due to rhizobial strain was observed. The concentration
      of GA(1) in lima bean stems was generally higher than that observed in the
      nodule, whereas concentrations of the other GAs measured were lower. In contrast
      with the nodule, GA concentrations in lima bean stems were not greater in plants
      inoculated with strain 127E14, and in some cases the slower growing plants
      inoculated with strain 127E15 actually had higher levels of GA(20), GA(19), and
      GA(44). Thus, there were major differences in concentrations of the precursors to
      GA(1) in nodules formed by the two bacterial strains, which were positively
      correlated with the observed elongation growth. These results support the
      hypothesis that the rhizobial strain modifies the endogenous GA status of the
      symbiotic system. This alteration in GA balance within the plant, presumably,
      underlies the observed growth response.

PMID- 16653230
TI  - Amide-Linked Indoleacetic Acid Conjugates May Control Levels of Indoleacetic Acid
      in Germinating Seedlings of Phaseolus vulgaris.
AB  - We have shown that amide-linked IAA (indole-3-acetic acid) conjugates accumulated
      to high levels during maturation of bean seeds (K. Bialek and J.D. Cohen [1989]
      Plant Physiol 91: 775-779). In the present study, we were interested in the fate
      of these and other IAA conjugates during seed germination. The content of amide
      linked conjugates of IAA in cotyledons declined dramatically during the first
      hours of imbibition. The rate of decline slowed markedly during the period of the
      resumption of axis growth. The level of amide-linked IAA conjugates in cotyledons
      remained relatively high after almost 1 week of germination. The decline of IAA
      conjugates in cotyledons was followed by a steady increase in the content of both
      free and amide-linked IAA in the embryonic axes. Amide-linked IAA conjugates were
      also present in the axes cultured on agar after the cotyledons were removed,
      which suggests that de novo production of these IAA conjugates occurs in the axis
      of germinating bean seedlings. A comparison of relative amounts of free and
      conjugated IAA in the axes of intact seedlings and axes cultured on agar showed
      lower levels of free IAA and higher levels of conjugated IAA in much slower
      growing isolated axes. These results suggest a more general role for IAA
      conjugates in the control of seedling growth than simply to serve as a seed
      storage form of auxin.

PMID- 16653231
TI  - Electrically induced protoplast fusion using pulse electric fields for
      dielectrophoresis.
AB  - The formation of protoplast chains in suspensions of isolated pea (Pisum sativum
      cv Ran 1) mesophyll protoplasts induced by electric fields was studied. The chain
      formation induced by a sine-wave field (2 V, peak to peak; 500-0.1 kHz) was
      compared to that induced by an alternating pulse field (1 V, amplitude; 0.1-0.4
      kHz). An increased number of dielectrophoretically paired protoplasts, formation
      of protoplast chains in the presence of CaCl(2) up to 5 mm, and protoplast fusion
      in the presence of 3 mm CaCl(2) were found when the pulse field was applied. The
      present results suggest the possibility of electrically induced protoplast fusion
      at cation concentrations that prevent fusion when sine-wave fields are applied.

PMID- 16653232
TI  - Organization of Ripening and Ethylene Regulatory Regions in a Fruit-Specific
      Promoter from Tomato (Lycopersicon esculentum).
AB  - Tomato (Lycopersicon esculentum) fruit ripening is initiated by an increase in
      ethylene hormone concentration. E8 gene transcription is fruit-specific and is
      activated at the onset of ripening and in unripe fruit treated with exogenous
      ethylene. To understand how E8 gene transcription is controlled during ripening,
      we analyzed the effect of deletions of flanking DNA sequences on E8 gene
      expression in transgenic tomato fruit. We found that a minimum of three 5' and
      one 3' regions influence E8 gene expression during fruit ripening. DNA sequences
      that confer responsiveness to exogenous ethylene in unripe fruit are distinct
      from DNA sequences that are sufficient for expression during fruit ripening.

PMID- 16653233
TI  - Characterization of Overexpressed cDNAs Isolated from a Hormone-Autonomous,
      Radiation-Induced Tumor Tissue Line of Arabidopsis thaliana.
AB  - To investigate the molecular mechanisms of hormonal control of growth, we
      constructed a subtracted cDNA library enriched for sequences expressed more in a
      hormone-autonomous, radiation-induced tumor tissue line of Arabidopsis thaliana
      than in normal, hormone-dependent callus. Ten cDNA clones, which are expressed
      1.3- to 10-fold more in the tumor line, were isolated and partially
      characterized. The clones differ greatly in their level of expression in tumor
      tissue and in their pattern of expression in plant organs. Southern blot
      hybridization and sequence analysis showed that this group contains three pairs
      of closely related clones. Northern blot analysis indicates that one pair of
      clones represents two members of a gene family that are expressed in different
      plant organs. One of the isolated sequences shows strong sequence similarity to a
      cDNA encoding a lipid transfer protein. Two sequences are highly similar to those
      of previously described membrane channel proteins but have different organ
      specificities. Two other cDNAs have significant sequence similarity to glycine
      rich proteins and hydroxy-proline-rich glycoproteins. When used to probe Southern
      blots, none of the cDNAs identified polymorphisms between tumor and callus DNA,
      which might be expected if their overexpression were due to local genome
      rearrangements induced by radiation. The diversity observed among these 10 clones
      suggests that some are likely to be involved in tumorous growth and not simply
      specific to a certain cell or tissue type present in the tumor.

PMID- 16653234
TI  - Structure-Activity Relationships of Abscisic Acid Analogs Based on the Induction
      of Freezing Tolerance in Bromegrass (Bromus inermis Leyss) Cell Cultures.
AB  - The induction of freezing tolerance in bromegrass (Bromus inermis Leyss) cell
      culture was used to investigate the activity of absisic acid (ABA) analogs.
      Analogs were either part of an array of 32 derived from systematic alterations to
      four regions of the ABA molecule or related, pure optical isomers. Alterations
      were made to the functional group at C-1 (acid replaced with methyl ester,
      aldehyde, or alcohol), the configuration at C-2, C-3 (cis double bond replaced
      with trans double bond), the bond order at C-4, C-5 (trans double bond replaced
      with a triple bond), and ring saturation (C-2', C-3' double bond replaced with a
      single bond so that the C-2' methyl and side chain were cis). All deviations in
      structure from ABA reduced activity. A cis C-2, C-3 double bond was the only
      substituent absolutely required for activity. Overall, acids and esters were more
      active than aldehydes and alcohols, cyclohexenones were more active than
      cyclohexanones, and dienoic and acetylenic analogs were equally active. The
      activity associated with any one substituent was, however, markedly influenced by
      the presence of other substituents. cis, trans analogs were more active than
      their corresponding acetylenic analogs unless the C-1 was an ester.
      Cyclohexenones were more active than cyclohexanones regardless of oxidation level
      at C-1. An acetylenic side chain decreased the activity of cyclohexenones but
      increased the activity of cyclohexanones relative to their cis, trans
      counterparts. Trends suggested that for activity the configuration at C-1' has to
      be the same as in (S)-ABA, in dihydro analogs the C-2'-methyl and the side chain
      must be cis, small positional changes of the 7'-methyl are tolerable, and the C-1
      has to be at the acid oxidation level.

PMID- 16653235
TI  - Isolation and characterization of the tricarboxylate transporter from pea
      mitochondria.
AB  - The tricarboxylate transporter was solubilized from pea (Pisum sativum)
      mitochondria with Triton X-114, partially purified over a hydroxylapatite column,
      and reconstituted in phospholipid vesicles. The proteoliposomes exchanged
      external [(14)C]citrate for internal citrate or malate but not for preloaded d,l
      isocitrate. Similarly, although external malate, succinate, and citrate competed
      with [(14)C]citrate in the exchange reaction, d,l-isocitrate and
      phosphoenolpyruvate did not. This tricarboxylate transporter differed from the
      equivalent activity from animal tissues in that it did not transport isocitrate
      and phosphoenolpyruvate. In addition, tricarboxylate transport in isolated plant
      mitochondria, as well as that measured with the partially purified and
      reconstituted transporter, was less active than the transporter isolated from
      animal tissues.

PMID- 16653236
TI  - Evidence for the Existence of Two Essential and Proximal Cysteinyl Residues in
      NADP-Malic Enzyme from Maize Leaves.
AB  - Incubation of maize (Zea mays) leaf NADP-malic enzyme with monofunctional and
      bifunctional N-substituted maleimides results in an irreversible inactivation of
      the enzyme. Inactivation by the monofunctional reagents, N-ethylmaleimide (NEM)
      and N-phenylmaleimide, followed pseudo-first-order kinetics. The maximum
      inactivation rate constant for phenylmaleimide was 10-fold higher than that for
      NEM, suggesting a possible hydrophobic microenvironment of the residue(s)
      involved in the modification of the enzyme. In contrast, the inactivation
      kinetics with the bifunctional maleimides, ortho-, meta-, and para
      phenylenebismaleimide, were biphasic, probably due to different reactivities of
      the groups reacting with the two heads of these bifunctional reagents, with a
      possible cross-linking of two sulfhydryl groups. The inactivation by mono and
      bifunctional maleimides was partially prevented by Mg(2+) and l-malate, and NADP
      prevented the inactivation almost totally. Determination of the number of
      reactive sulfhydryl groups of the native enzyme with [(3)H]NEM in the absence or
      presence of NADP showed that inactivation occurred concomitantly with the
      modification of two cysteinyl residues per enzyme monomer. The presence of these
      two essential residues was confirmed by titration of sulfhydryl groups with
      [(3)H]NEM in the enzyme previously modified by o-phenylenebismaleimide in the
      absence or presence of NADP.

PMID- 16653237
TI  - Purification and characterization of 1-aminocyclopropane-1-carboxylate N
      malonyltransferase from etiolated mung bean hypocotyls.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) N-malonyltransferase converts ACC, an
      immediate precursor of ethylene, to the presumably inactive product malonyl-ACC
      (MACC). This enzyme plays a role in ethylene production by reducing the level of
      free ACC in plant tissue. In this study, ACC N-malonyltransferase was purified
      3660-fold from etiolated mung bean (Vigna radiata) hypocotyls, with a 6% overall
      recovery. The final specific activity was about 83,000 nmol of MACC formed mg(-1)
      protein h(-1). The five-step purification protocol consisted of polyethylene
      glycol fractionation, Cibacron blue 3GA-agarose chromatography using salt
      gradient elution, Sephadex G-100 gel filtration, MonoQ anion-exchange
      chromatography, and Cibacron blue 3GA-agarose chromatography using malonyl-CoA
      plus ACC for elution. The molecular mass of the native enzyme determined by
      Sephadex G-100 chromatography was 50 +/- 3 kD. Protein from the final
      purification step showed one major band at 55 kD after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, indicating that ACC N-malonyltransferase is a
      monomer. The mung bean ACC N-malonyltransferase has a pH optimum of 8.0, an
      apparent K(m) of 0.5 mm for ACC and 0.2 mm for malonyl-coenzyme A, and an
      Arrhenius activation energy of 70.29 kJ mol(-1) degree(-1).

PMID- 16653238
TI  - Effects of solubilization on the inhibition of the p-type ATPase from maize roots
      by N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline.
AB  - The biochemical events utilized by transport proteins to convert the chemical
      energy from the hydrolysis of ATP into an electro-chemical gradient are poorly
      understood. The inhibition of the plasma membrane ATPase from corn (Zea mays L.)
      roots by N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) was compared to
      that of ATPase solubilized with N-tetradecyl-N,N-dimethyl-3-ammonio-1-propane
      sulfonate (3-14) to provide insight into the minimal functional unit. The
      chromatographic behavior of the 3-14-solubilized ATPase activity during size
      exclusion chromatography and glycerol gradient centrifugation indicated that the
      solubilized enzyme was in a monomeric form. Both plasma membrane-bound and
      solubilized ATPase were inhibited by EEDQ in a time- and concentration-dependent
      manner consistent with a first-order reaction. When the log of the reciprocal of
      the half-time for inhibition was plotted as a function of the log of the EEDQ
      concentration, straight lines were obtained with slopes of approximately 0.5 and
      1.0 for membrane-bound and 3-14-solubilized ATPase, respectively, indicating a
      change in the number of polypeptides per functional ATPase complex induced by
      solubilization with 3-14.

PMID- 16653239
TI  - Pleiotropy in Triazine-Resistant Brassica napus: Ontogenetic and Diurnal
      Influences on Photosynthesis.
AB  - Studies were conducted that supported the hypothesis that the mutation to the
      psbA plastid gene that confers S-triazine resistance (R) in Brassica napus also
      results in an altered diurnal pattern of photosynthetic carbon assimilation (A)
      relative to that of the susceptible (S) wild type, and that these patterns change
      over the ontogeny of a plant. Photosynthetic photon flux density, under closely
      controlled environmental conditions, was incrementally increased and decreased on
      either side of the midday maxima of 1150 to 1300 mumol quanta m(-2) s(-1). In all
      experiments, A approximately tracked the increasing and decreasing diurnal light
      levels. Younger (3- to 4-leaf) R plants had greater photosynthetic rates early
      and late in the diurnal light period, whereas those of S plants were greater
      during midday as well as during the photoperiod as a whole. These relative
      photosynthetic characteristics of R and S plants changed in several ways with
      ontogeny. As the plants aged during the vegetative phase of development, S plants
      gradually assimilated more carbon in the early, and then in the late, part of the
      day. At the end of the vegetative phase of development, R plant carbon
      assimilation was less relative to S plants at most times of the day, and was
      never greater. This relationship between the two biotypes dramatically changed
      with the onset of the reproductive phase (8(1/2) to 9(1/2) leaf) of plant
      development: R plants assimilated more carbon than S plants during all periods of
      the diurnal light period with the exception of the late part of the day. In
      addition to these differences in A, R plant stomatal function differed from that
      in S plants. R plant leaves were always cooler than S plant leaves under the same
      environmental and diurnal conditions. Correlated with this difference in leaf
      temperature were equal or greater total conductances to water vapor and
      intercellular CO(2) partial pressures in R compared to S leaves in most
      instances. These studies indicate a more complex pattern of photosynthetic carbon
      assimilation than previously observed. The photosynthetic superiority of one
      biotype relative to the other was a function of the time of day and the age of
      the plant. These studies also suggest that R plants may have an adaptive
      advantage over S plants in certain unfavorable ecological niches independent of
      the presence of S-triazine herbicides, such as cool, low-light environments early
      and late in the day, as well as late in the plants' development. This advantage
      could result in R biotypes appearing in populations of a species in greater
      numbers than plastidic mutation alone could cause.

PMID- 16653240
TI  - Characteristics of ethylene biosynthesis-inducing xylanase movement in tobacco
      leaves.
AB  - (125)I-Labeled ethylene biosynthesis-inducing xylanase (EIX) was used to study
      the movement of this protein in tobacco (Nicotiana tabacum) tissues. A
      biologically active (125)I-labeled EIX was obtained using chloramine-T as the
      oxidizing agent. Labeled EIX was detected in the far most edges of the leaf 5 min
      after it was applied to the petiole of a detached leaf. EIX was distributed
      uniformly throughout the leaf, including the mesophyll area within 5 to 15 min,
      after which there was only little change in the distribution of radioactivity in
      the leaf. (125)I-Labeled EIX was extracted from treated leaves, and EIX
      translocation in the leaf was blocked by preincubation of labeled EIX with anti
      EIX antibodies, indicating that the intact peptide moves in the leaf. Injection
      of anti-EIX antibodies into the intercellular spaces of the leaf mesophyll
      prevented induction of necrosis by EIX, suggesting the mesophyll as the site of
      EIX action. EIX was translocated both to upper and lower parts of the plant when
      applied to a whole plant through the petiole of a cut leaf. Radioactivity was
      found in all leaves and in the stem, although some leaves accumulated much more
      EIX than others; EIX was not found in the roots. There was no difference between
      the accumulation pattern of EIX in fresh and ethylene-treated leaves or between
      sensitive (Xanthi) and insensitive (Hicks) tobacco cultivars. These data support
      the hypothesis that intact EIX protein is translocated to the leaf mesophyll,
      where it directly elicits plant defense responses.

PMID- 16653241
TI  - Glutamine Induces the N-Dependent Accumulation of mRNAs Encoding
      Phosphoenolpyruvate Carboxylase and Carbonic Anhydrase in Detached Maize Leaf
      Tissue.
AB  - We have used detached leaves to study the N-dependent control of expression of
      phosphoenolpyruvate carboxylase (PEPC) and carbonic anhydrase (CA) genes in maize
      (Zea mays L. cv Golden Cross Bantam T51). Following supplementation with an N
      source and zeatin, PEPC and CA mRNA levels increased in leaves detached from N
      deficient maize plants. Addition of methionine sulfoximine (MSX), a specific
      inhibitor of glutamine synthetase, inhibited the nitrate-dependent increase of
      PEPC and CA mRNA but did not affect the glutamine-dependent increase of PEPC and
      CA mRNA levels. Glutamine levels in detached maize leaves treated with various N
      sources in the presence or absence of MSX correlated with the levels of PEPC and
      CA mRNA. We conclude that glutamine is the most likely effector for controlling
      the N-dependent expression of PEPC and CA in maize plants.

PMID- 16653242
TI  - Enlargement in chara studied with a turgor clamp : growth rate is not determined
      by turgor.
AB  - A new method, the turgor clamp, was developed to test the effects of turgor on
      cell enlargement. The method used a pressure probe to remove or inject cell
      solution and change the turgor without altering the external environment of the
      cell walls. After the injections, the cells were permanently at the new turgor
      and required no further manipulation. Internode cells of Chara corallina grew
      rapidly with the pressure probe in place when growth was monitored with a
      position transducer. Growth-induced water potentials were negligible and turgor
      effects could be studied simply. As turgor was decreased, there was a threshold
      below which no growth occurred, and only reversible elastic/viscoelastic changes
      could be seen. Above the threshold, growth was superimposed on the
      elastic/viscoelastic effects. The rate of growth did not depend on turgor.
      Instead, the rate was highly dependent on energy metabolism as shown by
      inhibitors that rapidly abolished growth without changing the turgor. However,
      turgors could be driven above the maximum normally attainable by the cell, and
      these caused growth to respond as though plastic deformation of the walls was
      beginning, but the deformation caused wounding. Growth was inhibited when turgor
      was changed with osmotica but not inhibited when similar changes were made with
      the turgor clamp. It was concluded that osmotica caused side effects that could
      be mistaken for turgor effects. The presence of a turgor threshold indicates that
      turgor was required for growth. However, because turgor did not control the rate,
      it appears incorrect to consider the rate to be determined by a turgor-dependent
      plastic deformation of wall polymers. Instead, above the turgor threshold, the
      rapid response to energy inhibitors suggests a control by metabolic reactions
      causing synthesis and/or extension of wall polymers.

PMID- 16653243
TI  - The identification of a heat-shock protein complex in chloroplasts of barley
      leaves.
AB  - In vivo radiolabeling of chloroplast proteins in barley (Hordeum vulgare L. cv
      Corvette) leaves and their separation by one-dimensional electrophoresis revealed
      at least seven heat-shock proteins between 24 and 94 kD, of which most have not
      been previously identified in this C(3) species. Fractionation into stromal and
      thylakoid membrane components showed that all chloroplast heat-shock proteins
      were synthesized on cytoplasmic ribosomes, translocated into the chloroplast, and
      located in the stroma. Examination of stromal preparations by native
      (nondissociating) polyacrylamide gel electrophoresis revealed the presence of a
      high-molecular mass heat-shock protein complex in barley. This complex was
      estimated to be 250 to 265 kD in size. Dissociation by denaturing polyacrylamide
      gel electrophoresis revealed a single protein component, a 32-kD heat-shock
      protein. The synthesis of this protein and the formation of the heat-shock
      protein complex were dependent on functional cytoplasmic ribosomes. Immunological
      studies showed that the heat-shock protein complex did not contain any proteins
      homologous to the alpha-subunit of ribulose bisphosphate carboxylase oxygenase
      subunit-binding protein. Other features about the complex included the absence of
      nucleic acid (RNA or DNA) and its nondissociation in the presence of Mg(2+)/ATP.
      These results suggest that the heat-shock protein complex in barley chloroplasts
      is a homogeneous octamer of 32-kD subunits.

PMID- 16653244
TI  - Inhibition of growth of cultured tobacco cells at low concentrations of
      lovastatin is reversed by cytokinin.
AB  - De novo synthesis of mevalonic acid, which is catalyzed by 3-hydroxy-3
      methylglutaryl coenzyme A reductase, is the first committed step in the formation
      of isoprenoid compounds. Various studies have shown that mevalonic acid-derived
      compounds are required for growth of plant and animal cells, a conclusion
      supported by the observation that cells treated with lovastatin (a potent
      inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase) cease growth. We
      show that Nicotiana tabacum BY-2 cells, which require exogenous auxin for growth
      in culture but do not require exogenous cytokinin, are growth inhibited by 1 mum
      lovastatin. However, these cells are capable of growing in the presence of 1 mum
      lovastatin if 8 mum zeatin is supplied in the medium. Furthermore, benzyladenine,
      kinetin, and thidiazuron effectively reverse the inhibition of growth of these
      cells at 1 mum lovastatin, whereas adenine and 6-methyladenine have no effect.
      These results demonstrate that restoration of growth to lovastatin-treated cells
      is cytokinin specific and is not caused by metabolism of cytokinin into other
      isoprenoid compounds. Cytokinin does not effectively reverse the effects of
      higher concentrations of lovastatin, but mevalonic acid does, consistent with the
      hypothesis that cytokinin biosynthesis is more sensitive to lovastatin than the
      biosynthesis of other essential isoprenoid compounds in tobacco cells. This
      observation suggests that lovastatin can be used to induce cytokinin dependence
      in cytokinin-autonomous tobacco cell cultures.

PMID- 16653245
TI  - Evidence for Activation of the Oxidative Pentose Phosphate Pathway during
      Photosynthetic Assimilation of NO(3) but Not NH(4) by a Green Alga.
AB  - Addition of NO(3) (-) to N-limited Selenastrum minutum during photosynthesis
      resulted in an immediate drop in the NADPH/NADP ratio and a slower increase of
      the NADH/NAD ratio. These changes were accompanied by a rapid decrease in glucose
      6-phosphate and increase in 6-phosphogluconate, indicating activation of glucose
      6-phosphate dehydrogenase and a role for the oxidation pentose phosphate pathway
      during photosynthetic NO(3) (-) assimilation. In contrast, the short-term changes
      in pyridine nucleotides and metabolites during photosynthetic assimilation of
      NH(4) (+) were not consistent with a stimulation of the oxidative pentose
      phosphate pathway.

PMID- 16653246
TI  - Effects of light and external solutes on the catabolism of nuclear-encoded
      stromal proteins in intact chloroplasts isolated from pea leaves.
AB  - The catabolism of nuclear-encoded stromal proteins was investigated in intact
      chloroplasts isolated mechanically from pea (Pisum sativum) leaves. Glutamine
      synthetase, phosphoribulokinase, and nitrite reductase (quantified by
      immunoblotting) were more rapidly degraded in the light than in the dark.
      Furthermore, the degradation rates depended on exogenously supplied metabolites.
      For example, 2-oxoglutarate accelerated the catabolism of all three enzymes in
      chloroplasts incubated in the light, whereas oxaloacetate stabilized glutamine
      synthetase and at the same time destabilized the other two enzymes.

PMID- 16653247
TI  - Effect of atmospheric pressure on maize root growth and ethylene production.
AB  - Maize (Zea mays) seedlings were exposed to elevated atmospheric pressures while
      growing in moist sand in open plastic envelopes to evaluate the effects of
      directly applied atmospheric pressure on ethylene production and root growth.
      Effects were evaluated after 24 h. The threshold pressures necessary to promote
      ethylene production and decrease root elongation were about 600 and 400 kPa,
      respectively. Direct atmospheric pressure, at levels up to 300 kPa, mimicked the
      control decrease in root diameter and increased diameter only slightly at 500 to
      1200 kPa. In contrast, in previous work it was shown that physical impedance
      resulting from compression of the growth medium by external application of 100
      kPa increased the ethylene production rate 4-fold and the root diameter 7-fold
      while reducing elongation 75% in 10 h. The relative insensitivity of roots to
      direct atmospheric pressure suggests that they perceive physical impedance,
      achieved experimentally by compressing the growth medium, via a surface mechanism
      rather than via a pressure-sensing mechanism.

PMID- 16653248
TI  - Substrate-Induced Stability of Glyceraldehyde 3-Phosphate Dehydrogenase from Mung
      Beans (Vigna radiata L.).
AB  - Time-dependent thermal inactivation of glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH) present in the extract of mung beans at different periods of germination
      showed biphasic kinetics in the 12-h germinated seeds but single exponential
      decay at 24 h of germination. The glyceraldehyde 3-phosphate (G-3-P)
      concentration in the deproteinated extracts was found to increase with period of
      germination up to 36 h, parallel to that of GAPDH activity. G-3-P was found to
      offer protection of the enzyme against thermal inactivation and trypsin
      digestion. It is suggested that accumulation of G-3-P in germinating mung beans
      may be of physiological significance and it might offer protection to the enzyme
      in vivo against thermal inactivation and proteolysis.

PMID- 16653249
TI  - Two Polypeptides in the Inner Chloroplast Envelope of Dunaliella tertiolecta
      Induced by Low CO(2).
AB  - Unicellular green algae have a mechanism for concentrating dissolved inorganic
      carbon (DIC) only when grown in low CO(2). To find proposed transporter
      protein(s) for DIC, we isolated intact chloroplasts from Dunaliella tertiolecta
      cells, separated the chloroplast envelopes by isopyknic centrifugation, and
      separated their polypeptides by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Two peptides of apparent molecular masses of 45 and 47 kD were
      constituents of the inner chloroplast envelope only if the cells had been adapted
      to low CO(2) in the light or grown in low CO(2). These two low CO(2)-induced
      peptides appear to be part of the algal DIC pump.

PMID- 16653250
TI  - Association of Phosphatidylinositol Kinase, Phosphatidylinositol Monophosphate
      Kinase, and Diacylglycerol Kinase with the Cytoskeleton and F-Actin Fractions of
      Carrot (Daucus carota L.) Cells Grown in Suspension Culture : Response to Cell
      Wall-Degrading Enzymes.
AB  - Phosphatidylinositol kinase (PI), phosphatidylinositol monophosphate (PIP)
      kinase, and diacylglycerol (DAG) kinase activities were detected in the
      cytoskeletal fraction isolated from microsomes and plasma membranes of carrot
      (Daucus carota L.) cells grown in suspension culture. The lipid kinase activities
      were associated with the actin filament fraction (F-actin fraction) isolated from
      the cytoskeleton. The PI and PIP kinase activity in the F-actin fraction
      significantly increased after cells were treated with Driselase, a mixture of
      cell wall-degrading enzymes; however, the DAG kinase activity in the F-actin
      fraction was unaffected by the Driselase treatment. These data indicate that at
      least one form of PI, PIP, and DAG kinase preferentially associates with actin
      filaments and/or actin binding proteins and that cytoskeletal-associated PI and
      PIP kinase activities can change in response to external stimulation.

PMID- 16653251
TI  - Genomic Nucleotide Sequence of a Soybean Seed Maturation Protein GmPM9 Gene.

PMID- 16653252
TI  - TOXICITY OF ALUMINUM ON SEEDLINGS AND ACTION OF CERTAIN IONS IN THE ELIMINATION
      OF THE TOXIC EFFECTS.

PMID- 16653253
TI  - OSMOTIC QUANTITIES OF PLANT CELLS IN GIVEN PHASES.

PMID- 16653254
TI  - DETERMINATION OF AMINO NITROGEN IN PLANT EXTRACTS.

PMID- 16653255
TI  - GROWTH, ORGANIC NITROGEN FRACTIONS, AND BUFFER CAPACITY IN RELATION TO HARDINESS
      OF PLANTS.

PMID- 16653257
TI  - A MECHANISM FOR CONTROLLED CONTINUOUS FLOW OF NUTRIENT SOLUTIONS.

PMID- 16653256
TI  - RELATIONSHIP BETWEEN NITROGEN FERTILIZATION AND CHLOROPHYLL CONTENT IN PINEAPPLE
      PLANTS.

PMID- 16653258
TI  - GROWTH MODIFICATIONS IN CITRUS SEEDLINGS GROWN FROM X-RAYED SEED.

PMID- 16653259
TI  - CAROTENE AND XANTHOPHYLL IN PINEAPPLES.

PMID- 16653260
TI  - LIGHT AS A FACTOR INFLUENCING THE DORMANCY OF LETTUCE SEEDS.

PMID- 16653261
TI  - A CASE OF CHANGE OF TROPIC RESPONSE.

PMID- 16653262
TI  - NOTES.

PMID- 16653263
TI  - LINKAGE BETWEEN OUTPUT OF ELECTRIC ENERGY BY POLAR TISSUES AND CELL OXIDATION.

PMID- 16653264
TI  - PHYSIOLOGY OF APPLE VARIETIES.

PMID- 16653265
TI  - DETERMINATION OF THE NITROGENOUS FRACTIONS IN VEGETATIVE TISSUE OF THE PEACH.

PMID- 16653266
TI  - CARBON DIOXIDE BALANCE AT HIGH LIGHT INTENSITIES.

PMID- 16653267
TI  - PROOF OF THE PRINCIPLE OF SUMMATION OF CELL E.M.F.'S.

PMID- 16653268
TI  - EFFECTS OF EXFLORATION ON PLANT METABOLISM.

PMID- 16653269
TI  - LIMITATIONS OF BLACKMAN'S LAW OF LIMITING FACTORS AND HARDER'S CONCEPT OF
      RELATIVE MINIMUM AS APPLIED TO PHOTOSYNTHESIS.

PMID- 16653270
TI  - TEMPERATURE AS A PREDETERMINING FACTOR IN THE DEVELOPMENT OF AVENA SATIVA.

PMID- 16653271
TI  - ABSORPTION OF SULPHUR DIOXIDE BY ALFALFA AND ITS RELATION TO LEAF INJURY.

PMID- 16653272
TI  - INFLUENCE OF DIFFERENT QUANTITIES OF MOISTURE IN A HEAVY SOIL ON RATE OF GROWTH
      OF PEARS.

PMID- 16653273
TI  - COLORIMETRIC DETERMINATION OF CAROTENE IN PLANT TISSUE.

PMID- 16653274
TI  - EFFECT OF SOLAR RADIATION ON TRANSPIRATION OF HELIANTHUS ANNUUS.

PMID- 16653275
TI  - METHOD FOR QUICKLY DETERMINING NITROGEN IN PLANTS, AND SOLUBLE NITROGEN AS A
      MEASURE OF THE NITROGEN AVAILABLE FOR ANABOLIC PROCESSES.

PMID- 16653276
TI  - DEVELOPMENT OF THE CHLOROPHYLL AND CAROTENOID PIGMENTS IN BARLEY SEEDLINGS.

PMID- 16653277
TI  - ABSORPTION SPECTRA OF ALPHA AND BETA CAROTENES AND LYCOPENE.

PMID- 16653278
TI  - CHEMICAL ANALYSIS OF PLANT TISSUE.

PMID- 16653279
TI  - DETERMINATION OF CARBOHYDRATES.

PMID- 16653280
TI  - DETERMINATION OF NITROGEN IN RELATIVELY SIMPLE COMPOUNDS.

PMID- 16653281
TI  - FORMATION OF CHLOROPHYLL AND THE BEGINNING OF PHOTOSYNTHESIS.

PMID- 16653283
TI  - NOTES.

PMID- 16653282
TI  - SALT CONCENTRATION AND REVERSIBILITY OF ICE-FORMATION AS RELATED TO THE HARDINESS
      OF ALFALFA.

PMID- 16653284
TI  - KARL RITTER VON GOEBEL.

PMID- 16653285
TI  - ACCUMULATION OF BORON BY RECIPROCALLY GRAFTED PLANTS.

PMID- 16653286
TI  - SALT TOLERANCE OF RUPPIA MARITIMA IN LAKES OF HIGH MAGNESIUM SULPHATE CONTENT.

PMID- 16653287
TI  - PHYSIOLOGICAL ROLE OF ASPARAGINE AND RELATED SUBSTANCES IN NITROGEN METABOLISM OF
      PLANTS.

PMID- 16653288
TI  - FACTORS INFLUENCING THE GROWTH AND YIELD OF POTATOES IN FLORIDA.

PMID- 16653289
TI  - STOCK-SCION CHEMISTRY AND THE FRUITING RELATIONSHIPS IN APPLE TREES.

PMID- 16653290
TI  - CHANGES IN NITROGEN COMPOUNDS IN THE WHEAT GRAIN AT DIFFERENT STAGES OF
      DEVELOPMENT.

PMID- 16653292
TI  - THERMAL CONDUCTIVITY OF STORED OATS WITH DIFFERENT MOISTURE CONTENT.

PMID- 16653291
TI  - DISTRIBUTION OF ROOTS IN POROUS AND NONPOROUS PLANT CONTAINERS.

PMID- 16653293
TI  - SULPHUR CONTENT OF PLANTS.

PMID- 16653294
TI  - BIOCHEMICAL PHASES OF OLEORESIN PRODUCTION.

PMID- 16653295
TI  - SOME EFFECTS OF THE PHOTOPERIOD ON DEVELOPMENT OF IMPATIENS BALSAMEA.

PMID- 16653296
TI  - FACTORS RENDERING THE PLASMOLYTIC METHOD INAPPLICABLE IN THE ESTIMATION OF
      OSMOTIC VALUES OF PLANT CELLS.

PMID- 16653297
TI  - PANTOTHENIC ACID AS A NUTRILITE FOR GREEN PLANTS.

PMID- 16653298
TI  - SOLUBILITY OF POTASSIUM IN CORN TISSUES.

PMID- 16653299
TI  - PHOTOELECTRIC APPARATUS FOR MEASURING LEAF AREAS.

PMID- 16653300
TI  - NOTES ON THE SUCROSE CONTENT AND DEXTROSE-LEVULOSE RATIO OF CALIFORNIA DRIED
      PRUNES.

PMID- 16653302
TI  - NOTES.

PMID- 16653301
TI  - ISOLATION AND DETERMINATION OF STARCH IN PLANT TISSUE.

PMID- 16653303
TI  - THE COURSE OF STONE CELL FORMATION IN PEAR FRUITS.

PMID- 16653304
TI  - STUDIES OF THE EFFECT OF ARTIFICIAL WIND ON GROWTH AND TRANSPIRATION IN
      HELIANTHUS ANNUUS.

PMID- 16653305
TI  - FURTHER STUDIES OF ELONGATION AND EXPANSION IN HELIANTHUS PHYTOMETERS.

PMID- 16653306
TI  - OSMOTIC PRESSURE AND WATER CONTENT OF PRAIRIE PLANTS.

PMID- 16653307
TI  - KINETICS OF AN INTRACELLULAR SYSTEM FOR RESPIRATION AND BIOELECTRIC POTENTIAL AT
      FLUX EQUILIBRIUM.

PMID- 16653308
TI  - PHYSIOLOGICAL PROBLEMS CONNECTED WITH THE USE OF SODIUM CHLORATE IN WEED CONTROL.

PMID- 16653309
TI  - PHYSICAL AND CHEMICAL PROPERTIES OF THE SOLUBLE POLYSACCHARIDES IN SWEET CORN.

PMID- 16653310
TI  - SEASONAL MARCH OF CARBOHYDRATES IN ELYMUS AMBIGUUS AND MUHLENBERGIA GRACILIS, AND
      THEIR REACTION UNDER MODERATE GRAZING USE.

PMID- 16653311
TI  - GROWTH AND SEASONAL CHANGES IN COMPOSITION OF OAK LEAVES.

PMID- 16653312
TI  - MODIFICATION OF LEAF STRUCTURE BY X-RAYS.

PMID- 16653313
TI  - OBSERVATIONS ON THE CRACKING OF CHERRIES.

PMID- 16653314
TI  - STREAMLINE FLOW AND THE MOVEMENT OF SOLUTES IN THE TRANSPIRATION STREAM.

PMID- 16653315
TI  - UNFREEZABLE AND FREEZABLE WATER EQUILIBRIUM IN PLANT TISSUES AS INFLUENCED BY SUB
      ZERO TEMPERATURES.

PMID- 16653316
TI  - HORMONES IN RELATION TO ROOT FORMATION ON STEM CUTTINGS.

PMID- 16653317
TI  - THE STOMATA AND TRANSPIRATION OF OAKS.

PMID- 16653318
TI  - PHOTOSYNTHESIS IN GRIMMIA MONTANA.

PMID- 16653319
TI  - SOME CHEMICAL ASPECTS OF CALCIUM DEFICIENCY EFFECTS ON PISUM SATIVUM.

PMID- 16653320
TI  - SOME EFFECTS OF FUEL OIL ON PLANTS.

PMID- 16653321
TI  - BRIEF PAPERS: EFFECT OF TITANOUS CHLORIDE ON THE FORMATION OF CHLOROPHYLL IN ZEA
      MAYS.

PMID- 16653322
TI  - NOTES.

PMID- 16653323
TI  - EFFECT OF PETROLEUM OILS ON THE RESPIRATION OF BEAN PLANTS, APPLE TWIGS AND
      LEAVES, AND BARLEY SEEDLINGS.

PMID- 16653324
TI  - CHANGES IN CARBOHYDRATE CONTENT OF WHEAT PLANTS DURING THE PROCESS OF HARDENING
      FOR DROUGHT RESISTANCE.

PMID- 16653325
TI  - EFFECT OF VARIATION IN LENGTH OF DAY ON GROWTH AND DORMANCY OF TREES.

PMID- 16653327
TI  - INFLUENCE OF THE CHLORIDE ION ON THE CONTENT OF CHLOROPHYLL IN THE LEAVES OF
      POTATOES.

PMID- 16653326
TI  - DISTRIBUTION OF CERTAIN SUGARS IN BOSC PEARS.

PMID- 16653328
TI  - THE CHLOROLYTIC ACTION OF SERUM.

PMID- 16653329
TI  - ANALYSIS OF OSMOTIC RELATIONS BY EXTENDING THE SIMPLIFIED METHOD.

PMID- 16653330
TI  - ADAPTATION OF THE MICRO-KJELDAHL METHOD FOR THE DETERMINATION OF NITROGEN IN
      PLANT TISSUES.

PMID- 16653331
TI  - RATE OF ADJUSTMENT OF LEAF TEMPERATURE TO INCIDENT ENERGY.

PMID- 16653332
TI  - PREPARATION OF SINTERED PYREX GLASS AERATORS FOR USE IN WATER CULTURE EXPERIMENTS
      WITH PLANTS.

PMID- 16653333
TI  - BREAKDOWN OF FRUIT AND VEGETABLE TISSUE DUE TO AN ELECTRIC CURRENT.

PMID- 16653334
TI  - NORMAL VIABILITY OF SEEDS AND BACTERIAL SPORES AFTER EXPOSURE TO TEMPERATURES
      NEAR THE ABSOLUTE ZERO.

PMID- 16653335
TI  - DIAGNOSIS OF PLANT TROUBLES WITH DIPHENYLAMINE.

PMID- 16653337
TI  - CHLOROPHYLLOMETRY.

PMID- 16653336
TI  - A DILATOMETER FOR PLANT MATERIALS.

PMID- 16653338
TI  - NOTES.

PMID- 16653339
TI  - SEASONAL STUDY OF TISSUE FUNCTION AND ORGANIC SOLUTE MOVEMENT IN THE SUNFLOWER.

PMID- 16653341
TI  - FURTHER STUDIES ON EXUDATION IN CUCURBITS.

PMID- 16653340
TI  - EFFECT OF AMMONIUM AND OF NITRATE NITROGEN ON THE COMPOSITION OF THE TOMATO
      PLANT.

PMID- 16653342
TI  - UTILIZATION OF GALACTOSE BY ASPERGILLUS NIGER AND PENICILLIUM GLAUCUM.

PMID- 16653343
TI  - THE SIXTH INTERNATIONAL BOTANICAL CONGRESS AT AMSTERDAM.

PMID- 16653344
TI  - PHOTOPERIODIC RESPONSES OF CERTAIN GREENHOUSE ANNUALS AS INFLUENCED BY INTENSITY
      AND WAVELENGTH OF ARTIFICIAL LIGHT USED TO LENGTHEN THE DAYLIGHT PERIOD.

PMID- 16653345
TI  - NITROGEN NUTRITION OF SUGAR CANE.

PMID- 16653346
TI  - SUSCEPTIBILITY OF SEVENTY SPECIES OF FLOWERING PLANTS TO X-RADIATION.

PMID- 16653347
TI  - LEAF TEMPERATURES AND THE COOLING OF LEAVES BY RADIATION.

PMID- 16653348
TI  - MAINTAINED ELECTRICAL POLARITIES IN REGION OF THE AXILLARY BUDS IN PHASEOLUS
      MULTIFLORUS.

PMID- 16653349
TI  - GROWTH AND WATER RELATIONS OF THE AVOCADO FRUIT.

PMID- 16653350
TI  - EFFECTS ON TREES OF AN ILLUMINATING GAS IN THE SOIL.

PMID- 16653351
TI  - GLUTAMINE METABOLISM OF THE BEET.

PMID- 16653352
TI  - HEMICELLULOSE CONSTITUENTS IN ALFALFA ROOTS.

PMID- 16653353
TI  - REDUCTION OF NITRATES TO NITRITES BY THE EXPRESSED JUICE OF HIGHER GREEN PLANTS.

PMID- 16653354
TI  - SIMPLE APPARATUS FOR THE QUANTITATIVE DETERMINATION OF PHOTOSYNTHETIC AND
      RESPIRATORY RATIOS.

PMID- 16653355
TI  - SOME RELATIONS BETWEEN LEAF AREA AND FRUIT SIZE IN TOMATOES.

PMID- 16653356
TI  - VARIATIONS IN THE CHIEF ASH CONSTITUENTS OF APPLES AFFECTED WITH BLOTCHY CORK.

PMID- 16653357
TI  - INFLUENCE OF IRRIGATION ON THE DEVELOPMENT OF THE ROOT SYSTEM OF SPRING WHEAT
      PLANTS.

PMID- 16653358
TI  - CARBOHYDRATES IN IRIDEAE LAMINARIOIDES (RHODOPHYCEAE).

PMID- 16653359
TI  - COLORIMETRIC DETERMINATION OF NARINGIN.

PMID- 16653361
TI  - F. A. F. C. WENT (1863-1935).

PMID- 16653360
TI  - NOTES.

PMID- 16653362
TI  - GENERAL NATURE OF THE PROCESS OF SALT ACCUMULATION BY ROOTS WITH DESCRIPTION OF
      EXPERIMENTAL METHODS.

PMID- 16653363
TI  - SALIENT FEATURES OF THE ROOT SYSTEM RELATIVE TO THE PROBLEM OF SALT ABSORPTION.

PMID- 16653364
TI  - RELATION OF TEMPERATURE AND TIME TO CARBON DIOXIDE PRODUCTION AND GROWTH IN
      CONTINUOUSLY AERATED MALT-AGAR CULTURES OF POLYSTICTUS VERSICOLOR.

PMID- 16653365
TI  - RESPIRATION AND METABOLISM IN ETIOLATED WHEAT SEEDLINGS AS INFLUENCED BY
      PHOSPHORUS NUTRITION.

PMID- 16653367
TI  - COMPARATIVE EFFECTS OF ALTERING LEAF TEMPERATURES AND AIR HUMIDITIES ON VAPOR
      PRESSURE GRADIENTS.

PMID- 16653366
TI  - TRANSPIRATION AS MODIFIED BY POTASSIUM.

PMID- 16653368
TI  - CHEMICAL NATURE OF THE OXYGEN-TRANSFERRING FERMENT OF RESPIRATION IN PLANTS.

PMID- 16653369
TI  - STIMULATION OF GROWTH OF SOY BEAN SEEDS BY SOFT X-RAYS.

PMID- 16653370
TI  - THE STATE OF WATER IN DUCTS AND TRACHEIDS.

PMID- 16653372
TI  - STERILIZATION OF CORN GRAINS WITH SODIUM HYPOCHLORITE.

PMID- 16653371
TI  - APPROXIMATE GERMINATION TEST FOR NON-AFTER-RIPENED PEACH SEED.

PMID- 16653373
TI  - VARIATIONS IN FLESHINESS OF TOMATO FRUITS AS AFFECTED BY FERTILIZATION.

PMID- 16653374
TI  - BEHAVIOR OF CITRUS FRUIT UNDER SPECIAL RESPIRATORY CONDITIONS AS AN EXPEDIENT
      INDEX OF VITALITY.

PMID- 16653375
TI  - BEHAVIOR OF STOMATA OF IRRIGATED WHEAT PLANTS.

PMID- 16653376
TI  - TOXICITY OF MERCURY VAPOR TO GERMINATING TOBACCO SEEDS.

PMID- 16653377
TI  - MODIFICATION OF ECKERSON METHOD FOR DETERMINING NITRATE REDUCASE.

PMID- 16653378
TI  - NOTES.

PMID- 16653379
TI  - VARIETAL DIFFERENCES IN THE PHOSPHORUS FEEDING CAPACITY OF PLANTS.

PMID- 16653380
TI  - UNFROZEN WATER IN APPLE SHOOTS AS RELATED TO THEIR WINTER HARDINESS.

PMID- 16653381
TI  - BIOCHEMICAL METHODS FOR THE STUDY OF NITROGEN METABOLISM IN PLANTS.

PMID- 16653382
TI  - TIME FACTOR IN UTILIZATION OF MINERAL NUTRIENTS BY HEMP.

PMID- 16653383
TI  - THE QUANTITATIVE MINERAL NUTRIENT REQUIREMENTS OF PLANTS.

PMID- 16653384
TI  - EFFECT OF BORON DEFICIENCY UPON THE STRUCTURE OF ZEA MAYS.

PMID- 16653385
TI  - TRANSPORT OF ROOT-FORMING HORMONE IN WOODY CUTTINGS.

PMID- 16653386
TI  - NUTRITIONAL REQUIREMENTS OF THE PATHOGENIC MOLD TRICHOPHYTON INTERDIGITALE.

PMID- 16653387
TI  - PHOTOPERIODIC RESPONSE OF CERTAIN LONG AND SHORT DAY PLANTS TO FILTERED RADIATION
      APPLIED AS A SUPPLEMENT TO DAYLIGHT.

PMID- 16653388
TI  - CHANGE IN ACTIVITY OF ENZYMES, SOLUBLE CARBOHYDRATES, AND INTENSITY OF
      RESPIRATION OF RICE SEEDS GERMINATING UNDER WATER.

PMID- 16653389
TI  - EFFECTS OF CARBON ARC LIGHT ON THE CHEMICAL COMPOSITION AND VEGETATIVE
      PROPAGATION OF TOMATO PLANTS GROWN WITH A LIMITED SUPPLY OF NITROGEN.

PMID- 16653390
TI  - RESPONSE OF QUACK GRASS TO DEFOLIATION AND FERTILIZATION.

PMID- 16653391
TI  - NITRITE AND FORMALDEHYDE FORMATION IN CERTAIN ALGAE.

PMID- 16653392
TI  - INFLUENCE OF THE CHLORIDE ION ON THE CONTENT OF CARBOHYDRATES IN POTATO LEAVES.

PMID- 16653393
TI  - HYDRATION STUDIES IN FRESH AND DRIED RED CLOVER ROOTS AND SHOOTS WITH REFERENCE
      TO PHYSICAL PROPERTIES AND CHEMICAL COMPOSITION OF TISSUE.

PMID- 16653394
TI  - A SIMPLE GAS ANALYSIS APPARATUS FOR THE MEASUREMENT OF PLANT RESPIRATION.

PMID- 16653395
TI  - NOTES.

PMID- 16653396
TI  - DISTRIBUTION OF THE VELOCITIES OF ABSORPTION OF WATER IN THE ONION ROOT.

PMID- 16653397
TI  - EFFECTS OF X-RAYS ON ZEA MAYS.

PMID- 16653398
TI  - LAG IN WATER ABSORPTION BY PLANTS IN WATER CULTURE WITH RESPECT TO CHANGES IN
      WIND.

PMID- 16653399
TI  - HYDROGEN ION CONCENTRATION AND SEXUAL EXPRESSION IN LYCHNIS DIOICA L.

PMID- 16653400
TI  - NITROGEN IN RELATION TO THE GROWTH OF CITRUS CUTTINGS IN SOLUTION CULTURES.

PMID- 16653401
TI  - EFFECTS OF PHOSPHORUS AND LIME IN REDUCING ALUMINUM TOXICITY OF ACID SOILS.

PMID- 16653402
TI  - SEASONAL FLUCTUATIONS IN GROWTH RATES OF EXCISED TOMATO ROOT TIPS.

PMID- 16653403
TI  - STRUCTURAL CHANGES PRODUCED IN LEAF TISSUE OF SOY BEAN PLANTS BY IRRADIATION OF
      THE DRY SEEDS WITH SOFT X-RAYS.

PMID- 16653405
TI  - EFFECT OF ETHYLENE CHLORHYDRIN AND THIOUREA ON ELODEA AND NITELLA.

PMID- 16653404
TI  - NUTRITIONAL STUDIES ON LOBLOLLY PINE.

PMID- 16653406
TI  - RELATION OF NUTRIENT SALT CONCENTRATION TO GROWTH OF THE TOMATO AND TO THE
      INCIDENCE OF BLOSSOM-END ROT OF THE FRUIT.

PMID- 16653407
TI  - SPECTROGRAPHIC METHOD FOR DETERMINING THE CARBON DIOXIDE EXCHANGE BETWEEN AN
      ORGANISM AND ITS SURROUNDINGS.

PMID- 16653408
TI  - CAROTENOIDS OF THE PEACH.

PMID- 16653410
TI  - NOTES.

PMID- 16653409
TI  - BORON CONTENT OF APPLES AT DIFFERENT STAGES OF DEVELOPMENT.

PMID- 16653411
TI  - THE FROST-HARDENING MECHANISM OF PLANT CELLS.

PMID- 16653412
TI  - EFFECT OF LIGHT ON SOLANINE SYNTHESIS IN THE POTATO TUBER.

PMID- 16653413
TI  - METHODS OF RESEARCH ON THE PHYSICAL PROPERTIES OF PROTOPLASM.

PMID- 16653414
TI  - EFFECT OF LIGHT INTENSITY ON THE PHOTOSYNTHETIC EFFICIENCY OF TOMATO PLANTS.

PMID- 16653415
TI  - EFFECT OF CERTAIN NUTRIENT DEFICIENCIES ON STOMATAL BEHAVIOR.

PMID- 16653416
TI  - THE CONTINUOUS MEASUREMENT OF PHOTOSYNTHESIS, RESPIRATION, AND TRANSPIRATION OF
      ALFALFA AND WHEAT GROWING UNDER FIELD CONDITIONS.

PMID- 16653417
TI  - RELATION OF SULPHUR DIOXIDE IN THE ATMOSPHERE TO PHOTOSYNTHESIS AND RESPIRATION
      OF ALFALFA.

PMID- 16653418
TI  - INFLUENCE OF WEAK ELECTRIC CURRENTS UPON THE GROWTH OF THE COLEOPTILE.

PMID- 16653419
TI  - ELECTRICAL POLARITY AND AUXIN TRANSPORT.

PMID- 16653421
TI  - EXCHANGE OF ELECTROLYTES BETWEEN ROOTS AND ACID SOLUTIONS.

PMID- 16653420
TI  - EFFECT OF ETHYLENE AND CERTAIN METABOLIC GASES UPON RESPIRATION AND RIPENING OF
      PEARS BEFORE AND AFTER COLD STORAGE.

PMID- 16653422
TI  - UREASE DISTRIBUTION IN PLANTS: GENERAL METHODS.

PMID- 16653423
TI  - A RECORDING POTENTIOMETER FOR USE IN PHYSIOLOGICAL INVESTIGATIONS.

PMID- 16653424
TI  - CONTRIBUTION TO THE KNOWLEDGE OF PLANT PHENOLASES.

PMID- 16653425
TI  - EFFECT OF ULTRAVIOLET RADIATION ON INDOLE-3-N-PROPIONIC ACID.

PMID- 16653426
TI  - FACTORS AFFECTING COLD RESISTANCE IN PLANTS.

PMID- 16653427
TI  - GAS CONTENT OF CRANBERRIES AND POSSIBLE RELATIONSHIP OF RESPIRATORY ACTIVITY TO
      KEEPING QUALITY.

PMID- 16653428
TI  - NATURE OF THE BLACKMAN REACTION IN PHOTOSYNTHESIS.

PMID- 16653429
TI  - TUBERIZATION OF THE COLORADO WILD POTATO AS AFFECTED BY X-RADIATION.

PMID- 16653430
TI  - CALCIUM AND BORON CONTENTS OF THE APPLE FRUIT AS RELATED TO THE INCIDENCE OF
      BLOTCHY CORK.

PMID- 16653432
TI  - NOTES.

PMID- 16653431
TI  - METHOD OF STIRRING GASES WITHIN A CLOSED CHAMBER.

PMID- 16653433
TI  - FIFTY YEARS OF PLANT PHYSIOLOGY IN AUSTRIA.

PMID- 16653434
TI  - FOLIAR DIAGNOSIS: PRINCIPLES AND PRACTICE.

PMID- 16653435
TI  - UREASE DISTRIBUTION IN CANAVALIA ENSIFORMIS.

PMID- 16653436
TI  - NUTRITIONAL CHARACTERISTICS OF CERTAIN WOOD-DESTROYING FUNGI, POLYPORUS BETULINUS
      FR., FOMES PINICOLA (FR.) COOKE, AND POLYSTICTUS VERSICOLOR FR.

PMID- 16653437
TI  - METHODS OF SAMPLING VISIBLE RADIATION.

PMID- 16653438
TI  - A PRECISE METHOD, WITH DETAILED CALIBRATION FOR THE DETERMINATION OF ABSORPTION
      COEFFICIENTS; THE QUANTITATIVE MEASUREMENT OF THE VISIBLE AND ULTRAVIOLET
      ABSORPTION SPECTRA OF ALPHA CAROTENE, BETA CAROTENE, AND LYCOPENE.

PMID- 16653439
TI  - ENZYME ACTIVITY IN COLD-HARDENED AND UNHARDENED RED CLOVER.

PMID- 16653440
TI  - WATER ABSORPTION IN THE COTTON PLANT AS AFFECTED BY SOIL AND WATER TEMPERATURES.

PMID- 16653441
TI  - FACTORS IN VARIETAL SUSCEPTIBILITY OF WALNUT FRUITS TO ATTACK BY THE WALNUT-HUSK
      FLY.

PMID- 16653442
TI  - POLAR TRANSPORT OF AUXIN AND ELECTRICAL POLARITY IN COLEOPTILE OF AVENA.

PMID- 16653443
TI  - CARBOHYDRATE CHANGES WITHIN THE NEEDLES OF PINUS PONDEROSA AND PSEUDOTSUGA
      TAXIFOLIA.

PMID- 16653444
TI  - SURVIVAL OF ISOLATED TOMATO ROOTS AT SUBOPTIMAL AND SUPRAOPTIMAL TEMPERATURES.

PMID- 16653445
TI  - SEPARATION FROM YEAST OF MATERIALS ESSENTIAL FOR GROWTH OF EXCISED TOMATO ROOTS.

PMID- 16653446
TI  - AMINO ACIDS IN THE NUTRITION OF EXCISED TOMATO ROOTS.

PMID- 16653448
TI  - DORMANCY AND GERMINATION OF FRAXINUS SEEDS.

PMID- 16653447
TI  - VITAMIN B(1) IN THE NUTRITION OF EXCISED TOMATO ROOTS.

PMID- 16653449
TI  - INFLUENCE OF HOST NUTRITION ON SYSTEMIC DEVELOPMENT OF TOBACCO MOSAIC.

PMID- 16653450
TI  - ABSORPTION SPECTRA OF SINGLE CHLOROPLASTS IN LIVING CELLS IN THE REGION FROM 664
      mmu TO 704 mmu.

PMID- 16653451
TI  - ON THE DETERMINATION OF PLANT ENZYMES.

PMID- 16653452
TI  - INCREASE OF TRANSPIRATION RATES OF TOMATO LEAVES DUE TO COPPER SPRAYS.

PMID- 16653453
TI  - PROOF OF THE FLUX EQUILIBRIUM RELATION.

PMID- 16653454
TI  - VALUE OF THE DYE-ADSORPTION TEST FOR PREDETERMINING THE DEGREE OF HARDINESS.

PMID- 16653455
TI  - ENVIRONMENTAL CONDITIONS INFLUENCING THE DEVELOPMENT OF TOMATO POCKETS OR PUFFS.

PMID- 16653456
TI  - PHOTOPERIODIC STIMULATION OF GROWTH BY ARTIFICIAL LIGHT AS A CAUSE OF WINTER
      KILLING.

PMID- 16653458
TI  - NOTES.

PMID- 16653457
TI  - DEVELOPMENT OF CAROTENOID PIGMENTS WITHOUT THE AID OF LIGHT.

PMID- 16653459
TI  - CHLOROPHYL IN SULTANINA GRAPES AND RAISINS.

PMID- 16653460
TI  - THE QUANTITY OF ETHYLENE PRESENT IN APPLES.

PMID- 16653461
TI  - A TEACHERS' FORUM.

PMID- 16653462
TI  - NOTES.

PMID- 16653463
TI  - ASSIMILATION OF AMMONIUM AND NITRATE NITROGEN FROM SOLUTION CULTURES BY ROOTS OF
      PANDANUS VEITCHI HORT., AND DISTRIBUTION OF THE VARIOUS NITROGEN FRACTIONS AND
      SUGARS IN THE STELE AND CORTEX.

PMID- 16653464
TI  - EFFECT OF ENVIRONMENTAL FACTORS UPON THE COLOR OF THE TOMATO AND THE WATERMELON.

PMID- 16653465
TI  - EFFECTS OF IONIZED AIR AND OZONE ON PLANTS.

PMID- 16653466
TI  - INTENSITY OF REMOVAL OF CATIONS FROM COTTON, CORN, AND SOY BEAN TISSUE BY
      FRACTIONAL ELECTRODIALYSIS.

PMID- 16653467
TI  - LEAF TEMPERATURES OF SUGAR CANE.

PMID- 16653468
TI  - SEASONAL VARIATION IN ELONGATION OF YOUNG SEEDLING RADICLES.

PMID- 16653469
TI  - APPLICATION OF THE CHLORATE METHOD FOR DETERMINING NITROGEN TO LIGHT, FLUFFY
      MATERIALS.

PMID- 16653470
TI  - PLANT PHYSIOLOGY IN THE U.S.S.R.

PMID- 16653472
TI  - SOME ABSORPTION SPECTRA OF LEAF EXTRACTS.

PMID- 16653471
TI  - UPWARD MOVEMENT OF INORGANIC SOLUTES AS AFFECTED BY A GIRDLE.

PMID- 16653473
TI  - EFFECT OF LIGHT ON CO(2) IN LEAVES.

PMID- 16653474
TI  - EFFECT OF HYDROGEN-ION CONCENTRATION ON CHLORELLA PHOTOSYNTHESIS.

PMID- 16653475
TI  - SOIL MOISTURE AS AN INDICATION OF ROOT DISTRIBUTION IN DECIDUOUS ORCHARDS.

PMID- 16653476
TI  - EFFECT OF SOIL MOISTURE ON THE RATE OF GROWTH OF LONGLEAF AND SLASH PINE
      SEEDLINGS.

PMID- 16653477
TI  - TIME FACTOR CONCERNED WITH FLUIDITY CHANGES IN WARMED AND COOLED CELLS OF ZYGNEMA
      AND SPIROGYRA.

PMID- 16653478
TI  - META- AND PYROPHOSPHATE WITHIN THE ALGAL CELL.

PMID- 16653479
TI  - BRIEF PAPERS: PREPARATION OF INULIN FOR USE IN ADSORPTION COLUMNS.

PMID- 16653480
TI  - BRIEF PAPERS: EFFECTS OF X-RAYS ON SEEDS.

PMID- 16653481
TI  - NOTES.

PMID- 16653482
TI  - UREASE DISTRIBUTION IN SOJA MAX.

PMID- 16653483
TI  - RECOVERY PROCESSES OF PONDEROSA PINE REPRODUCTION FOLLOWING INJURY TO YOUNG
      ANNUAL GROWTH.

PMID- 16653484
TI  - SPECIFIC FACTORS OTHER THAN AUXIN AFFECTING GROWTH AND ROOT FORMATION.

PMID- 16653485
TI  - BUD REGENERATION AND ELECTRICAL POLARITIES IN PHASEOLUS MULTIFLORUS.

PMID- 16653486
TI  - PROGRESS OF PLANT PHYSIOLOGICAL INVESTIGATIONS IN CZECHOSLOVAKIA.

PMID- 16653487
TI  - PRELIMINARY EXPERIMENTS ON THE RELATION OF GROWTH-PROMOTING SUBSTANCES TO THE
      REST PERIOD IN FRUIT TREES.

PMID- 16653488
TI  - PLANT DIASTASE IN EVIDENCE AS TO THE FORMATION AND STRUCTURE OF STARCH GRANULES.

PMID- 16653489
TI  - RESPIRATORY BLOCK IN THE DORMANT SPORES OF NEUROSPORA TETRASPERMA.

PMID- 16653490
TI  - AMMONIUM NUTRITION AND METABOLISM OF ETIOLATED SEEDLINGS.

PMID- 16653491
TI  - STRUCTURE OF THE STARCH GRANULE.

PMID- 16653492
TI  - A CHEMICAL AND PHYSIOLOGICAL STUDY OF TRAUMATIN, A PLANT WOUND HORMONE.

PMID- 16653493
TI  - EFFECT OF CERTAIN IONS, USED SINGLY AND IN COMBINATION, ON THE GROWTH AND
      POTASSIUM, CALCIUM, AND MAGNESIUM ABSORPTION OF THE BEAN PLANT.

PMID- 16653494
TI  - CHEMICAL AND SPECTROSCOPIC ANALYSIS OF PHLOEM EXUDATE AND PARENCHYMA SAP FROM
      SEVERAL SPECIES OF PLANTS.

PMID- 16653495
TI  - CARBOHYDRATE METABOLISM OF VITIS VINIFERA: HEMICELLULOSE.

PMID- 16653496
TI  - ACCESSORY SALTS IN THE NUTRITION OF EXCISED TOMATO ROOTS.

PMID- 16653497
TI  - INFLUENCE OF FOLIAGE SPRAYS ON DROUGHT RESISTANCE OF CONIFERS.

PMID- 16653498
TI  - FORMATION OF NITRATE IN DETACHED GREEN LEAVES OF SWISS CHARD AND TOMATO.

PMID- 16653499
TI  - FORMATION OF CAROTENOIDS AND CHLOROPHYLLS IN ETIOLATED BARLEY SEEDLINGS EXPOSED
      TO RED LIGHT.

PMID- 16653500
TI  - A PHOTOELECTRIC PHOTOMETER FOR CHEMICAL ANALYSIS.

PMID- 16653501
TI  - APPLICABILITY OF KUNDT'S RULE TO CHLOROPHYLL.

PMID- 16653502
TI  - NOTES.

PMID- 16653503
TI  - HORMONES AND THE ANALYSIS OF GROWTH.

PMID- 16653504
TI  - EXANTHEMA IN PEAR, AND COPPER DEFICIENCY.

PMID- 16653505
TI  - WATER RELATIONS IN BRYOPHYLLUM CALYCINUM SUBJECTED TO SEVERE DRYING.

PMID- 16653506
TI  - ASSIMILATION OF AMMONIUM AND NITRATE BY PINEAPPLE PLANTS GROWN IN NUTRIENT
      SOLUTIONS AND ITS EFFECTS ON NITROGENOUS AND CARBOHYDRATE CONSTITUTENTS.

PMID- 16653507
TI  - ELECTRICAL POLARITY AND AUXIN TRANSPORT.

PMID- 16653508
TI  - CONDUCTIVITY MEASUREMENTS OF PLANT SAP.

PMID- 16653509
TI  - BEHAVIOR OF PECTIC SUBSTANCES AND NARINGIN IN GRAPEFRUIT IN THE FIELD AND IN
      STORAGE.

PMID- 16653510
TI  - AUXIN PRODUCTION IN SEEDLINGS OF DWARF MAIZE.

PMID- 16653511
TI  - CORRELATION BETWEEN GROWTH OF EXCISED ROOT TIPS AND TYPES OF FOOD STORED IN THE
      SEED.

PMID- 16653512
TI  - INTERMEDIATES OF VITAMIN B(1) AND THE GROWTH OF TORULA.

PMID- 16653513
TI  - RELATIONSHIP OF THE ORGANIC ACIDS OF TOBACCO TO THE INORGANIC BASIC CONSTITUENTS.

PMID- 16653514
TI  - GROWTH OF CABBAGE SEEDLINGS IN SAND CULTURE, AS AFFECTED BY DELAYED APPLICATION
      OF NUTRIENT SALTS.

PMID- 16653515
TI  - ISOLATION OF A HEXOSEMONOPHOSPHATE FROM PEA LEAVES.

PMID- 16653516
TI  - INFLUENCE OF OSMOTIC PRESSURE ON SPORULATION BY BACILLUS SUBTILIS.

PMID- 16653517
TI  - INFLUENCE OF THE LENGTH OF DAY ON THE DORMANCY OF TREE SEEDLINGS.

PMID- 16653518
TI  - EFFECT OF DROUGHT ON PROTOPLASMIC ELASTICITY.

PMID- 16653519
TI  - NOTES.

PMID- 16653520
TI  - DIURNAL FLUCTUATION IN ROOT PRESSURE.

PMID- 16653521
TI  - FOLIAR DIAGNOSIS: ITS RELATION TO THE OPTIMUM NUTRITION OF THE POTATO.

PMID- 16653522
TI  - EFFECTS OF A LIMITING ELEMENT ON THE ABSORPTION OF INDIVIDUAL ELEMENTS AND ON THE
      ANION: CATION BALANCE IN WHEAT.

PMID- 16653523
TI  - RELATION BETWEEN LIGHT AND THE ELECTRIC POLARITY OF CHARA.

PMID- 16653524
TI  - A STUDY OF MINERAL NUTRITION OF WHEAT AS INFLUENCED BY FERTILIZER COMBINATIONS.

PMID- 16653525
TI  - SALT TOLERANCE OF PLANTS AT VARIOUS TEMPERATURES.

PMID- 16653526
TI  - TRANSLOCATION IN PLANTS.

PMID- 16653527
TI  - ICE FORMATION AND THE DEATH OF PLANT CELLS BY FREEZING.

PMID- 16653528
TI  - TEMPERATURE EFFECTS UPON THE GROWTH OF EXCISED ROOT TIPS.

PMID- 16653529
TI  - CARBOHYDRATES OF BEAN PLANTS AFTER TREATMENT WITH INDOLE-3-ACETIC ACID.

PMID- 16653530
TI  - THE MIRSKY-PAULING THEORY OF THE STRUCTURE OF NATIVE, DENATURED, AND COAGULATED
      PROTEINS, AND SOME THEORETICAL ASPECTS OF THE EVOLUTION OF OXYGEN FROM THE
      IRRADIATED GREEN PLANT.

PMID- 16653531
TI  - HERITABLE VARIATIONS IN CHLOROPHYLL.

PMID- 16653532
TI  - NICOTINIC ACID AND THE GROWTH OF ISOLATED PEA EMBRYOS.

PMID- 16653534
TI  - EFFECT OF SUN AND SHADE ON PIGMENT DEVELOPMENT.

PMID- 16653533
TI  - EFFECTS OF FLUE DUST ON THE GROWTH OF SUNFLOWER AND GOLDEN WAX BEAN.

PMID- 16653536
TI  - NOTES.

PMID- 16653535
TI  - TEACHING METHODS IN PLANT PHYSIOLOGY.

PMID- 16653537
TI  - EFFECT OF POTASH MANURING ON THE PRODUCTION OF ORGANIC MATTER.

PMID- 16653538
TI  - ESTIMATION OF PROTOPLASMIC PERMEABILITY FROM PLASMOLYTIC TESTS.

PMID- 16653539
TI  - EFFECT OF ETHYLENE ON CERTAIN CHEMICAL CHANGES ASSOCIATED WITH THE RIPENING OF
      PEARS.

PMID- 16653540
TI  - GROWTH BEHAVIOR OF ONE-MILLIMETER EXCISED ROOT TIPS.

PMID- 16653541
TI  - TRANSPIRATION AND THE ABSORPTION OF MINERAL SALTS.

PMID- 16653542
TI  - TIME AND TEMPERATURE OF PROTOPLASMIC COAGULATION.

PMID- 16653543
TI  - A METHOD FOR THE TREATMENT OF CUTTINGS AND ROOTS OF THE PECAN WITH ROOT-INDUCING
      CHEMICALS.

PMID- 16653544
TI  - PLANT PHYSIOLOGY IN THE WOMEN'S COLLEGES.

PMID- 16653545
TI  - NOTES.

PMID- 16653546
TI  - ROLE OF NITROGEN IN FUNGOUS THERMOGENESIS.

PMID- 16653547
TI  - TRANSLOCATION OF CARBOHYDRATES IN THE SUGAR BEET.

PMID- 16653548
TI  - FOLIAR DIAGNOSIS: THE INFLUENCE OF THE SOIL ON THE ACTION OF FERTILIZERS.

PMID- 16653549
TI  - ANTAGONISM OF CERTAIN ELEMENTS ESSENTIAL TO PLANTS TOWARD CHEMICALLY RELATED
      TOXIC ELEMENTS.

PMID- 16653550
TI  - THE RELATION OF CABBAGE HARDINESS TO BOUND WATER, UNFROZEN WATER, AND CELL
      CONTRACTION WHEN FROZEN.

PMID- 16653551
TI  - CARBOHYDRATE AND RESPIRATORY METABOLISM IN THE ISOLATED STARVING LEAF OF WHEAT.

PMID- 16653552
TI  - DISTRIBUTION OF DIFFERENT NITROGEN FRACTIONS, SUGARS AND OTHER SUBSTANCES IN
      VARIOUS SECTIONS OF THE PINEAPPLE PLANT GROWN IN SOIL CULTURES AND RECEIVING
      EITHER AMMONIUM OR NITRATE SALTS.

PMID- 16653553
TI  - EFFECT OF TEMPERATURE UPON THE RATE OF ELONGATION OF THE STEMS OF ASPARAGUS GROWN
      UNDER FIELD CONDITIONS.

PMID- 16653554
TI  - PROBLEMS IN THE STORAGE OF CUT CARNATIONS.

PMID- 16653555
TI  - APPLICATION OF THE CERIC SULPHATE METHOD IN THE ANALYSIS OF CARBOHYDRATES IN THE
      ROOTS OF LEPIDIUM AND CONVOLVULUS.

PMID- 16653556
TI  - EFFECT OF HEAVY AND LATE APPLICATIONS OF NITROGENOUS FERTILIZER ON THE COLD
      RESISTANCE OF KENTUCKY BLUEGRASS.

PMID- 16653557
TI  - SUGGESTIONS FOR THE USE OF WARBURG RESPIROMETERS IN PLANT PHYSIOLOGICAL
      INVESTIGATIONS.

PMID- 16653558
TI  - RELATION BETWEEN FRUIT SIZE AND FOOD SUPPLY IN THE TOMATO.

PMID- 16653559
TI  - ORGANIC ACID METABOLISM OF THE BUCKWHEAT PLANT.

PMID- 16653560
TI  - DETERMINATION OF AMMONIA AND AMIDE NITROGEN IN CONNECTION WITH THE CHLORATE
      METHOD FOR NITROGEN IN PLANT TISSUES.

PMID- 16653562
TI  - ELECTRICAL RESPONSE OF PHASEOLUS MULTIFLORUS TO ELECTRICAL CURRENTS.

PMID- 16653561
TI  - DETERMINATION OF CONSTANTS FOR CURVES OF WATER ABSORPTION BY DRY ORGANIC
      SUBSTANCES.

PMID- 16653563
TI  - TRANSPORT OF INORGANIC IONS IN POLAR PLANT TISSUES.

PMID- 16653564
TI  - THE ESSENTIALITY OF CERTAIN ELEMENTS IN MINUTE QUANTITY FOR PLANTS WITH SPECIAL
      REFERENCE TO COPPER.

PMID- 16653565
TI  - ALKALOIDS FROM SANGUINARIA CANADENSIS AND THEIR INFLUENCE ON GROWTH OF
      PHYMATOTRICHUM OMNIVORUM.

PMID- 16653566
TI  - SEASONAL SUGAR VARIATIONS IN ALFALFA.

PMID- 16653568
TI  - CONDITION OF CHLOROPHYLL IN THE LEAF.

PMID- 16653567
TI  - RELATIONS OF PLANTS TO MINUTE DOSES OF INHIBITIVE SUBSTANCES.

PMID- 16653569
TI  - AN AUTOMATIC PLANT IRRIGATOR AND RECORDER.

PMID- 16653570
TI  - NOTES.

PMID- 16653571
TI  - DANIEL TREMBLY MACDOUGAL: PIONEER PLANT PHYSIOLOGIST.

PMID- 16653572
TI  - ATMOSPHERIC HUMIDITY AND TEMPERATURE IN RELATION TO THE WATER SYSTEM OF PLANTS
      AND SOILS.

PMID- 16653573
TI  - STUDIES ON ANTAGONISTIC PHENOMENA AND CATION ABSORPTION IN TOBACCO IN THE
      PRESENCE AND ABSENCE OF MANGANESE AND BORON.

PMID- 16653574
TI  - TRANSPIRATION AND PHYSICO-CHEMICAL PROPERTIES OF LEAVES AS RELATED TO DROUGHT
      RESISTANCE IN LOBLOLLY PINE AND SHORTLEAF PINE.

PMID- 16653575
TI  - SOME INVESTIGATIONS ON THE ASSIMILATION OF APPLE LEAVES.

PMID- 16653576
TI  - INFLUENCE OF CERTAIN AMINO ACIDS AND OF NICOTINIC ACID UPON THE NICOTINE CONTENT
      OF TOBACCO LEAVES.

PMID- 16653577
TI  - GROWTH OF WHEAT PLANTS FROM DRY AND SOAKED IRRADIATED GRAINS.

PMID- 16653578
TI  - GREENHOUSE STUDIES OF THE EFFECT OF CLIPPING THE TOPS OF ALFALFA AT VARIOUS
      HEIGHTS ON THE PRODUCTION OF ROOTS, RESERVE CARBOHYDRATES, AND TOP GROWTH.

PMID- 16653579
TI  - EQUIPMENT FOR THE GROWING OF PLANTS AT CONTROLLED TEMPERATURES.

PMID- 16653580
TI  - GLYCINE IN THE NUTRITION OF EXCISED TOMATO ROOTS.

PMID- 16653581
TI  - EFFECTS OF CATIONS AND ANIONS ON PROTOPLASMIC ELASTICITY.

PMID- 16653582
TI  - CHARACTERISTICS OF THE TYROSINASE SYSTEM IN POTATOES WHICH BLACKEN AFTER BOILING.

PMID- 16653583
TI  - CARBOHYDRATES OF WHEAT LEAVES.

PMID- 16653584
TI  - STIMULATION OF GERMINATION OF DORMANT LETTUCE SEED BY SULPHUR COMPOUNDS.

PMID- 16653585
TI  - SOME FACTORS CONTRIBUTING TO TOMATO PUFFING.

PMID- 16653586
TI  - ELECTRODIALYSIS OF PEA SEEDS.

PMID- 16653587
TI  - INTERPRETATION OF COMPARATIVE GROWTHS OF FUNGAL COLONIES GROWING ON DIFFERENT
      SOLID SUBSTRATA.

PMID- 16653588
TI  - THE CALIBRATION OF A CONSTANT RECORDING ILLUMINOMETER WHEN THE SENSITIVE SAMPLING
      SURFACE IS HORIZONTAL.

PMID- 16653589
TI  - MOLYBDENUM AS AN ESSENTIAL ELEMENT FOR HIGHER PLANTS.

PMID- 16653590
TI  - SINTERED PYREX GLASS AERATORS.

PMID- 16653591
TI  - NITROGEN NUTRITION IN RELATION TO YIELD AND QUALITY OF GRAPEFRUIT.

PMID- 16653592
TI  - NOTES.

PMID- 16653593
TI  - RESPIRATION OF ACORNS AS RELATED TO TEMPERATURE AND AFTER-RIPENING.

PMID- 16653595
TI  - CHANGES IN THE COMPOSITION AND RATE OF GROWTH ALONG THE DEVELOPING STEM OF
      ASPARAGUS.

PMID- 16653594
TI  - DISTRIBUTION OF NITROGENOUS FRACTIONS, SUGARS, AND OTHER SUBSTANCES IN ANANAS
      GROWN IN DARKNESS VERSUS DAYLIGHT.

PMID- 16653596
TI  - FOLIAR DIAGNOSIS: PHYSIOLOGICAL BALANCE BETWEEN THE BASES LIME, MAGNESIA, AND
      POTASH.

PMID- 16653597
TI  - EFFECTS OF CERTAIN INSECTICIDES AND INERT MATERIALS UPON THE TRANSPIRATION RATE
      OF BEAN PLANTS.

PMID- 16653598
TI  - POLYSACCHARIDES OF THE VEGETATIVE TISSUES OF MAIZE.

PMID- 16653599
TI  - A STUDY OF DEVELOPMENTAL CHANGES IN COMPOSITION OF THE MACADAMIA.

PMID- 16653600
TI  - THE EFFECT OF HOST NUTRITION ON CONCENTRATION OF TOBACCO-MOSAIC VIRUS.

PMID- 16653601
TI  - FLORAL DEVELOPMENT OF CERTAIN SPECIES AS INFLUENCED BY X-RADIATION OF BUDS.

PMID- 16653602
TI  - SOME EFFECTS OF METAL SALTS ON YEAST DEHYDROGENASE.

PMID- 16653603
TI  - PECTIC CONTENT OF PLANT MATERIALS.

PMID- 16653604
TI  - PRODUCTION AND CONSUMPTION OF ETHYLENE BY ETHYLENE-TREATED BANANAS.

PMID- 16653605
TI  - EVIDENCE FOR THE ESSENTIALITY OF SILICON FOR GROWTH OF THE BEET PLANT.

PMID- 16653606
TI  - A METERING PUMP FOR SMALL VOLUMES OF SOLUTION.

PMID- 16653607
TI  - METERING PUMP AND TURNTABLE ARRANGEMENT FOR SUPPLYING MEASURED QUANTITIES OF
      NUTRIENT SOLUTION SUCCESSIVELY TO ANY NUMBER OF CULTURE VESSELS.

PMID- 16653608
TI  - CONVENIENT SEEDLING SUPPORT FOR GROWING PLANTS IN WATER CULTURE.

PMID- 16653609
TI  - NOTES.

PMID- 16653610
TI  - HENRY HORATIO DIXON.

PMID- 16653611
TI  - RESPONSES OF THE BEAN PLANT TO CALCIUM DEFICIENCY.

PMID- 16653613
TI  - DETERMINATION OF MINERAL ELEMENTS IN PLANT TISSUE.

PMID- 16653612
TI  - LIGHT-MASS ABSORPTION DURING PHOTOSYNTHESIS.

PMID- 16653614
TI  - ABSORPTION AND MOVEMENT OF RADIOPHOSPHORUS IN BEAN SEEDLINGS.

PMID- 16653615
TI  - RESPONSES OF VARIOUS SPRING WHEATS TO VERNALIZATION.

PMID- 16653616
TI  - EFFECT OF CHLOROPICRIN IN THE SOIL SOLUTION ON PLANT GROWTH.

PMID- 16653617
TI  - EFFECT OF NITRATE OF SODA ON THE RESPONSE OF SPINACH TO LENGTH OF DAY.

PMID- 16653618
TI  - QUANTITATIVE STUDY OF THE PRODUCTION OF ETHYLENE BY RIPENING MCINTOSH APPLES.

PMID- 16653619
TI  - FLAX VARIETIES COMPARED.

PMID- 16653620
TI  - NOTES.

PMID- 16653621
TI  - METABOLIC PROCESSES OF POTATO DISCS UNDER CONDITIONS CONDUCIVE TO SALT
      ACCUMULATION.

PMID- 16653622
TI  - ROOT RESISTANCE AS A CAUSE OF DECREASED WATER ABSORPTION BY PLANTS AT LOW
      TEMPERATURES.

PMID- 16653623
TI  - SEASONAL VARIATIONS IN THE PRODUCTION OF PLANT PIGMENTS.

PMID- 16653624
TI  - EFFECTS OF BORON DEFICIENCY AND EXCESS ON PLANTS.

PMID- 16653625
TI  - FACTORS AFFECTING REGENERATION OF THE HORSERADISH ROOT.

PMID- 16653626
TI  - THE ABSORPTION OF CARBON DIOXIDE BY UNILLUMINATED LEAVES.

PMID- 16653627
TI  - DISTRIBUTION OF NITROGENOUS AND CARBOHYDRATE FRACTIONS AND OTHER SUBSTANCES IN
      EXPOSED AND COVERED PINEAPPLE SISTER SHOOTS.

PMID- 16653628
TI  - RESPIRATION OF CEREAL GRAINS AND FLAXSEED.

PMID- 16653629
TI  - EFFECT OF LIGHT INTENSITY ON THE DEVELOPMENT OF THE PHOTOSYNTHETIC MECHANISM.

PMID- 16653630
TI  - AUXIN IN MARINE ALGAE.

PMID- 16653631
TI  - SPIRAL SYSTEMS IN THE ORGANIZATION OF LIVING MATERIAL.

PMID- 16653632
TI  - RELATION BETWEEN QUANTITY OF CHLOROPHYLL AND CAPACITY FOR PHOTOSYNTHESIS.

PMID- 16653633
TI  - EXPERIMENTS ON PHOTOPERIOD IN RELATION TO THE VEGETATIVE GROWTH OF PLANTS.

PMID- 16653634
TI  - OBSERVATIONS ON THE DEVELOPMENT OF CERTAIN CELL-WALL CONSTITUENTS OF FORAGE
      PLANTS.

PMID- 16653635
TI  - SOIL TEMPERATURE AND GROWTH OF MARQUIS WHEAT.

PMID- 16653636
TI  - EFFECT OF CERTAIN THIOCYANATE SPRAYS ON FOLIAGE AND FRUIT IN APPLES.

PMID- 16653637
TI  - DOES "C.P. GRADE" SUCROSE CONTAIN IMPURITIES SIGNIFICANT FOR THE NUTRITION OF
      EXCISED TOMATO ROOTS?

PMID- 16653638
TI  - SUCROSE VS. DEXTROSE AS CARBOHYDRATE SOURCE FOR EXCISED TOMATO ROOTS.

PMID- 16653639
TI  - KUNDT'S RULE.

PMID- 16653640
TI  - NOTES.

PMID- 16653641
TI  - STARCH FORMATION IN TOBACCO PLANTS DEFICIENT IN POTASSIUM.

PMID- 16653642
TI  - RELATION OF pH TO GROWTH IN CITRUS.

PMID- 16653643
TI  - THE BALANCE SHEET OF METABOLITES FOR POTATO DISCS SHOWING THE EFFECT OF SALTS AND
      DISSOLVED OXYGEN ON METABOLISM AT 23 degrees C.

PMID- 16653644
TI  - EFFECT OF SOIL MOISTURE ON GROWTH AND TRANSPIRATION IN HELIANTHUS ANNUUS.

PMID- 16653645
TI  - STORAGE OF ROOT RESERVES IN RHODES GRASS.

PMID- 16653646
TI  - THE MINERAL COMPOSITION OF THE ALCOHOLIC EXTRACT OF POTATO LEAVES AND ITS
      RELATIONSHIP TO CROP YIELDS.

PMID- 16653647
TI  - SOME ASPECTS OF MINERAL NUTRITION IN RELATION TO BISON FLAX.

PMID- 16653649
TI  - MEASUREMENT OF THE RESPIRATORY QUOTIENT OF PLANT TISSUES IN A CONSTANT GASEOUS
      ENVIRONMENT.

PMID- 16653648
TI  - AUXITHALS SYNTHESIZED BY SOME FILAMENTOUS FUNGI.

PMID- 16653650
TI  - MICRO DETERMINATION OF SOME CONSTITUENTS OF PLANT ASH.

PMID- 16653651
TI  - RESPONSE OF EXCISED TOMATO ROOTS TO beta (-4-METHYLTHIAZOLYL-5) -ALANINE.

PMID- 16653652
TI  - SPECIFICITY OF NICOTINIC ACID AS A GROWTH FACTOR FOR ISOLATED PEA ROOTS.

PMID- 16653653
TI  - TRANSMISSION SPECTROGRAMS OF LEAF EXTRACTS.

PMID- 16653654
TI  - IMPROVEMENTS IN THE SIMPLIFIED METHOD FOR OSMOTIC MEASUREMENTS.

PMID- 16653655
TI  - ISOLATION OF THE ALKALOIDS, BERBERINE AND BERBAMINE, FROM MAHONIA SWASEYI.

PMID- 16653656
TI  - CRITICISM OF A RECENT PAPER ON THE PECTIC CONTENT OF PLANT MATERIALS.

PMID- 16653657
TI  - NOTES.

PMID- 16653658
TI  - A STUDY OF THE PIGMENTS PRODUCED IN DARKNESS BY CERTAIN GREEN ALGAE.

PMID- 16653659
TI  - USE OF TENSIOMETERS IN REGULATING WATERING IN FOREST NURSERIES.

PMID- 16653660
TI  - THE EFFECT OF VARIOUS WAVEBANDS OF SUPPLEMENTARY RADIATION ON THE PHOTOPERIODIC
      RESPONSE OF CERTAIN PLANTS.

PMID- 16653661
TI  - EFFECTS OF ENVIRONMENTAL FACTORS ON OXIDIZING ENZYMES OF ROSE MALLOW SEEDS.

PMID- 16653663
TI  - PHYSIOLOGICAL FACTORS OPERATIVE IN ICE-SHEET INJURY OF ALFALFA.

PMID- 16653662
TI  - STUDIES ON THE PROTOPLASMIC NATURE OF STIMULATION AND ANESTHESIA. II.

PMID- 16653664
TI  - THE RELATIVE RATES OF DESTRUCTION OF PECTIN IN MACERATES OF VARIOUS CITRUS
      FRUITS.

PMID- 16653665
TI  - MOVEMENT OF ORGANIC SOLUTES IN THE SAUSAGE TREE KIGELIA AFRICANA.

PMID- 16653666
TI  - DETERMINATION OF AMMONIA, GLUTAMINE, AND ASPARAGINE AMIDE NITROGEN IN PLANT
      JUICE.

PMID- 16653667
TI  - SOME CHEMICAL AND RESPIRATIONAL CHANGES IN THE PAPAYA FRUIT DURING RIPENING, AND
      THE EFFECTS OF COLD STORAGE ON THESE CHANGES.

PMID- 16653668
TI  - A SEMI-MICRO METHOD FOR THE DETERMINATION OF REDUCING SUGARS.

PMID- 16653669
TI  - SAND CULTURE STUDIES OF THE USE OF SALINE AND ALKALINE WATERS IN GREENHOUSES.

PMID- 16653670
TI  - INFLUENCE OF AUXINS ON REPRODUCTION OF LEMNA MAJOR.

PMID- 16653671
TI  - AN ESTIMATION OF THE VOLUME OF WATER MADE AVAILABLE BY ROOT EXTENSION.

PMID- 16653673
TI  - SOME EFFECTS OF STANNOUS SULPHATE AND STANNIC CHLORIDE ON SEVERAL HERBACEOUS
      PLANTS.

PMID- 16653672
TI  - DETERMINATION OF THE NITROGEN FRACTIONS IN ATLAS AND MILO SORGHUM PLANTS.

PMID- 16653674
TI  - THE LITHIUM METHOD OF MEASURING THE EXTENT OF CORN ROOT SYSTEMS.

PMID- 16653675
TI  - MONTHLY ABSORPTION OF NUTRIENTS FROM THE SOIL BY THE PERFECTION PIMIENTO PLANT.

PMID- 16653676
TI  - NOTES.

PMID- 16653677
TI  - A CRITICAL STUDY OF THE NUTRITIONAL REQUIREMENTS OF PHYMATOTRICHUM OMNIVORUM.

PMID- 16653678
TI  - FOLIAR DIAGNOSIS STUDY OF CLIMATIC INFUENCES ON THE NUTRITION OF SPRING AND FALL
      GROWN GREENHOUSE TOMATOES.

PMID- 16653679
TI  - EFFECT OF THE FORM OF THE AVAILABLE NITROGEN ON THE CALCIUM DEFICIENCY SYMPTOMS
      IN THE BEAN PLANT.

PMID- 16653680
TI  - ROOT MODIFICATIONS INDUCED IN VICIA FABA BY IRRADIATING DRY SEEDS WITH SOFT X
      RAYS.

PMID- 16653681
TI  - DEHYDRATION INJURY AND RESISTANCE.

PMID- 16653682
TI  - EFFECTS OF PERIODS OF WARM WEATHER UPON THE WINTER HARDENED CONDITION OF A PLANT.

PMID- 16653683
TI  - EFFECT OF MANGANESE DEFICIENCY UPON THE HISTOLOGY OF LYCOPERSICUM ESCULENTUM.

PMID- 16653684
TI  - COMPARISON OF RATES OF WATER INTAKE IN CONTIGUOUS REGIONS OF INTACT AND ISOLATED
      ROOTS.

PMID- 16653685
TI  - TOXICITY OF SELENIUM-CONTAINING PLANTS AS A MEANS OF CONTROL FOR RED SPIDERS.

PMID- 16653686
TI  - LACK OF INHIBITION OF LATERAL BUDS BY THE GROWTH-PROMOTING SUBSTANCE PHENYLACETIC
      ACID.

PMID- 16653687
TI  - AUTOMATIC WATERING OF EXPERIMENTAL PLOTS.

PMID- 16653688
TI  - COMPARATIVE TRANSMISSION SPECTROGRAMS OF AN IRRADIATED LEAF EXTRACT.

PMID- 16653689
TI  - HEXOSE-PHOSPHATE IN ALFALFA HAY.

PMID- 16653690
TI  - NOTES.

PMID- 16653691
TI  - THE DETERMINATION OF SELECTED CHEMICAL CHARACTERISTICS OF SOIL WHICH AFFECT THE
      GROWTH AND COMPOSITION OF PLANTS.

PMID- 16653692
TI  - SIGNIFICANCE OF PHLOEM EXUDATE OF CUCURBITA PEPO WITH REFERENCE TO TRANSLOCATION
      OF ORGANIC MATERIALS.

PMID- 16653693
TI  - THE EFFECT OF SALT CONCENTRATION UPON THE METABOLISM OF POTATO DISCS AND THE
      CONTRASTED EFFECT OF POTASSIUM AND CALCIUM SALTS WHICH HAVE A COMMON ION.

PMID- 16653694
TI  - INHIBITION OF INCREASE AND ACTIVITY OF TOBACCO-MOSAIC VIRUS UNDER NITROGEN
      DEFICIENT CONDITIONS.

PMID- 16653695
TI  - RESPONSE OF SEEDLINGS TO VARIOUS WAVEBANDS OF LOW INTENSITY IRRADIATION.

PMID- 16653696
TI  - ABSORPTION AND UTILIZATION OF RADIOACTIVE CARBON DIOXIDE BY SUNFLOWER LEAVES.

PMID- 16653697
TI  - NATURE OF BOUND WATER IN COLLOIDAL SYSTEMS.

PMID- 16653698
TI  - UNEQUAL DISTRIBUTION OF SOLUBLE SOLIDS IN THE PULP OF CITRUS FRUITS.

PMID- 16653699
TI  - TOLERANCE OF SHORTLEAF PINE SEEDLINGS FOR SOME VARIATIONS IN SOLUBLE CALCIUM AND
      H-ION CONCENTRATION.

PMID- 16653700
TI  - THE EFFECT OF AERATION ON GROWTH OF THE TOMATO IN NUTRIENT SOLUTION.

PMID- 16653701
TI  - LACTIC ACID FORMATION IN ALCOHOLIC FERMENTATION BY YEAST.

PMID- 16653702
TI  - PRESSURE-COMPOSITION RELATIONSHIPS OF THE GAS IN THE MARINE BROWN ALGA,
      NEREOCYSTIS LUETKEANA.

PMID- 16653704
TI  - PLANT CULTURE EQUIPMENT.

PMID- 16653703
TI  - X-RAY EFFECTS ON THE GROWTH AND REPRODUCTION OF WHEAT.

PMID- 16653705
TI  - ANTAGONISTIC ACTION OF CHLORIDES ON THE TOXICITY OF IODIDES TO CORN.

PMID- 16653706
TI  - SOME COMMENTS ON THE MECHANISM OF PHLOEM TRANSPORT.

PMID- 16653707
TI  - pH DETERMINATION IN PLANT TISSUE.

PMID- 16653708
TI  - POTASSIUM DETERMINATION BY THE COBALTINITRITE METHOD AS AFFECTED BY TEMPERATURE
      AND pH.

PMID- 16653709
TI  - CHANGES IN CHEMICAL COMPOSITION OF TWIGS AND BUDS OF YELLOW POPLAR DURING THE
      DORMANT PERIOD.

PMID- 16653710
TI  - A PRESS FOR RECOVERY OF FLUIDS FROM PLANT TISSUES.

PMID- 16653711
TI  - SEED IMPRESSIONS ON PLASTIC FILMS.

PMID- 16653712
TI  - COMPARATIVE TRANSMISSION SPECTROGRAMS OF DIFFERENT CONCENTRATIONS OF LEAF
      EXTRACT.

PMID- 16653713
TI  - NOTES.

PMID- 16653714
TI  - SIGNIFICANT ROLES OF TRACE ELEMENTS IN THE NUTRITION OF PLANTS.

PMID- 16653715
TI  - WATER BALANCE IN THE ONION ROOT: RELATION OF VOLUME INTAKE TO VOLUME EXUDATE OF
      EXCISED ROOTS AND ISOLATED ROOT SEGMENTS.

PMID- 16653716
TI  - AGENCIES AFFECTING THE PRODUCTION OF SUBSTANCE B BY RHIZOPUS SUINUS.

PMID- 16653717
TI  - EFFECTS OF pH AND THE COMPONENTS OF BICARBONATE AND PHOSPHATE BUFFERED SOLUTIONS
      ON THE METABOLISM OF POTATO DISCS AND THEIR ABILITY TO ABSORB IONS.

PMID- 16653719
TI  - WATER UPTAKE AND ROOT GROWTH AS INFLUENCED BY INEQUALITIES IN THE CONCENTRATION
      OF THE SUBSTRATE.

PMID- 16653718
TI  - ACCUMULATION OF ARSENIC IN THE SHOOTS OF SUDAN GRASS AND BUSH BEAN.

PMID- 16653721
TI  - FACTORS AFFECTING ROOT FORMATION OF PHASEOLUS VULGARIS.

PMID- 16653720
TI  - INFLUENCE OF SOIL MOISTURE ON PHOTOSYNTHESIS, RESPIRATION, AND TRANSPIRATION OF
      APPLE LEAVES.

PMID- 16653722
TI  - TRANSFORMATION OF SUGARS IN EXCISED BARLEY SHOOTS.

PMID- 16653723
TI  - REFRACTIVE INDEX AS AN ESTIMATE OF QUALITY BETWEEN AND WITHIN MUSKMELON FRUITS.

PMID- 16653724
TI  - SOME EFFECTS OF SUPPLEMENTARY ILLUMINATION WITH MAZDA LAMPS ON THE CARBOHYDRATE
      AND THE NITROGEN METABOLISM OF THE ASTER (CALLISTEPHUS CHINENSIS VAR. HEART OF
      FRANCE).

PMID- 16653725
TI  - AN INEXPENSIVE INTEGRATING LIGHT RECORDER.

PMID- 16653726
TI  - PRODUCTION OF SOLUTES IN GROWING EPIDERMAL CELLS.

PMID- 16653727
TI  - AUTOMATIC CONDUCTIVITY MEASUREMENTS OF CO(2).

PMID- 16653728
TI  - A HIGHLY SIMPLIFIED THERMIONIC CONTROL OF TEMPERATURE.

PMID- 16653729
TI  - SPECTROSCOPIC ANALYSIS OF PLANT EXTRACTS FOR CHLOROPHYLLS a AND b.

PMID- 16653730
TI  - PHOTOSYNTHESIS WITH RADIOACTIVE CARBON, AND THE DISTRIBUTION OF THE INTERMEDIATE
      PRODUCTS IN THE PLANT CELL.

PMID- 16653731
TI  - NOTES.

PMID- 16653732
TI  - INFLUENCE OF NITROGEN SUPPLY ON THE RATE OF MULTIPLICATION OF TOBACCO-MOSAIC
      VIRUS.

PMID- 16653733
TI  - THE EFFECT OF HIGH CONCENTRATIONS OF CARBON DIOXIDE ON THE GLUTAMINE AND
      ASPARAGINE METABOLISM OF THE SUGAR BEET.

PMID- 16653734
TI  - SELECTIVE ABSORPTION OF CATIONS BY HIGHER PLANTS.

PMID- 16653735
TI  - INFLUENCE OF BORDEAUX MIXTURE AND ITS COMPONENT PARTS ON TRANSPIRATION AND
      APPARENT PHOTOSYNTHESIS OF APPLE LEAVES.

PMID- 16653736
TI  - FORMIC ACID FORMATION IN ALCOHOLIC FERMENTATION.

PMID- 16653737
TI  - SUCCINIC ACID AS A METABOLITE IN PLANT TISSUES.

PMID- 16653738
TI  - BOUND WATER IN PLANT SAP AND SOME EFFECTS OF TEMPERATURE AND NUTRITION THEREON.

PMID- 16653739
TI  - THE RESPIRATORY METABOLISM OF McINTOSH APPLES DURING ONTOGENY, AS DETERMINED AT
      22 degrees C.

PMID- 16653740
TI  - THE EFFECT ON BARLEY SEEDLINGS OF SOME INTER-RELATIONS OF CATIONS AND ANIONS IN A
      THREE-SALT NUTRIENT SOLUTION.

PMID- 16653741
TI  - MOISTURE DISTRIBUTION IN SOIL IN CONTAINERS.

PMID- 16653742
TI  - EFFECTS OF INJURIES CAUSED BY THE CICADA, MAGICICADA SEPTENDECIM, ON THE LATER
      GROWTH OF TREES.

PMID- 16653743
TI  - A SIEVE TUBE TRANSLOCATION MODEL.

PMID- 16653745
TI  - NOTES.

PMID- 16653744
TI  - USE OF NITRIC ACID IN CONTROL OF pH AND NITRATE LEVELS IN NUTRIENT SOLUTION.

PMID- 16653746
TI  - EFFECTS OF SOME CHEMICALLY INERT DUSTS UPON THE TRANSPIRATION RATE OF YELLOW
      COLEUS PLANTS.

PMID- 16653747
TI  - DIFFERENCES IN GROWTH LIMITATION OF CERTAIN PLANTS BY MAGNESIUM AND MINOR ELEMENT
      DEFICIENCIES.

PMID- 16653748
TI  - INFLUENCE OF SOIL TEMPERATURE ON THE DEVELOPMENT OF COLONIAL BENT GRASS.

PMID- 16653749
TI  - SOME RESPONSES OF THE BEAN PLANT TO CHLORATE AND PERCHLORATE IONS.

PMID- 16653750
TI  - INFLUENCE OF CARBON DIOXIDE ON RESPONSE OF ASPERGILLUS NIGER TO TRACE ELEMENTS.

PMID- 16653751
TI  - A SIMPLE, RAPID METHOD FOR DETERMINATION OF LEAF CAROTENE.

PMID- 16653752
TI  - INFLUENCE OF VITAMIN B(1) ON THE GROWTH OF AGROSTIS TENUIS AND BRASSICA ALBA.

PMID- 16653753
TI  - BRIEF PAPERS: EFFECT OF VITAMIN B(1) ON THE GROWTH OF RICE PLANTS.

PMID- 16653754
TI  - BRIEF PAPERS: EFFECT OF BORAX APPLICATIONS ON THE INCIDENCE OF RUST ON FLAX.

PMID- 16653756
TI  - NOTES.

PMID- 16653755
TI  - BRIEF PAPERS: THE CIRCULAR REVOLVING BRUSH AS A TISSUE DISINTEGRATOR.

PMID- 16653757
TI  - EFFECTS OF GROWTH REGULATING CHEMICALS ON THE OPENING OF VEGETATIVE AND FLORAL
      BUDS OF PEACH AND PEAR.

PMID- 16653758
TI  - LIME-INDUCED CHLOROSIS OF CITRUS IN RELATION TO SOIL FACTORS.

PMID- 16653759
TI  - SOME FACTORS INFLUENCING THE UTILIZATION OF INORGANIC NITROGEN BY THE ROOT ROT
      FUNGUS.

PMID- 16653760
TI  - EFFECTS OF PRETREATMENT ON THE ESTIMATION OF ORGANIC ACIDS IN PLANT TISSUES.

PMID- 16653761
TI  - EFFECT OF SUBSOIL ACIDITY AND FERTILITY ON THE GROWTH OF SEEDLING BLACK LOCUST
      AND GREEN ASH.

PMID- 16653762
TI  - RESPIRATION STUDIES OF DEVELOPING JONATHAN APPLES.

PMID- 16653763
TI  - EFFECT OF EXTERNAL FACTORS ON TOMATO PIGMENTS AS STUDIED BY CHROMATOGRAPHIC
      METHODS.

PMID- 16653764
TI  - ALFRED URSPRUNG.

PMID- 16653765
TI  - "VEGETABLE DYNAMICKS" AND PLANT TISSUE CULTURES.

PMID- 16653766
TI  - COMPOSITION OF ALCOHOLIC LEAF EXTRACT AND THE ENTIRE LEAF OF IRISH POTATOES AS
      INDICES OF SOIL FERTILITY.

PMID- 16653767
TI  - EFFECT OF TEMPERATURE ON THE RESPIRATION RATE AND THE RESPIRATORY QUOTIENT OF
      SOME VEGETABLES.

PMID- 16653768
TI  - ANALYSIS OF PLANT EXTRACTS FOR CHLOROPHYLLS a AND b BY A PHOTOELECTRIC
      SPECTROPHOTOMETRIC METHOD.

PMID- 16653769
TI  - SPECIFIC BIOLOGICAL ACTIVITY OF TOBACCO-MOSAIC VIRUS AS INFLUENCED BY AGE OF
      LESION AND NITROGEN SUPPLY.

PMID- 16653770
TI  - LIMITATIONS OF AUTO-IRRIGATORS FOR CONTROLLING SOIL MOISTURE UNDER GROWING
      PLANTS.

PMID- 16653771
TI  - GROWTH, AUXIN, AND TROPISMS IN DECAPITATED AVENA COLEOPTILES.

PMID- 16653772
TI  - A NON-OSMOTIC FORCE IN THE WATER RELATIONS OF POTATO TUBERS DURING STORAGE.

PMID- 16653774
TI  - GROWTH OF RHIZOPUS SUINUS AS AFFECTED BY CERTAIN GROWTH FACTORS.

PMID- 16653773
TI  - STUDY OF RESPIRATION IN HEALTHY AND MOSAIC-INFECTED TOBACCO PLANTS.

PMID- 16653775
TI  - A STUDY OF THE CHEMICAL COMPOSITION OF SOYBEANS DURING MATURATION.

PMID- 16653776
TI  - APPLICATION OF THE LIQUID EXTRACTION METHOD FOR THE DETERMINATION OF TOTAL
      ORGANIC ACIDS IN PLANT SAP.

PMID- 16653777
TI  - THE NECESSITY OF ZINC FOR PINUS RADIATA.

PMID- 16653778
TI  - RESPONSE OF CYPERUS ROTUNDUS L. TO FIVE MOISTURE LEVELS.

PMID- 16653779
TI  - THE IRON-MANGANESE RATIO IN RELATION TO THE RESPIRATORY CO(2) AND DEFICIENCY
      TOXICITY SYMPTOMS IN SOYBEANS.

PMID- 16653780
TI  - FAILURE OF ROOT TIPS OF TOMATO SEEDLINGS GERMINATED FROM X-RAYED SEEDS TO GROW IN
      VITRO.

PMID- 16653781
TI  - STERILIZATION TECHNIQUE FOR GRASS SEEDS.

PMID- 16653782
TI  - NOTES.

PMID- 16653783
TI  - THE PREPARATION AND ABSORPTION SPECTRA OF FIVE PURE CAROTENOID PIGMENTS.

PMID- 16653784
TI  - EFFECT OF SALINE SUBSTRATE ON HOURLY LEVELS OF CARBOHYDRATES AND INORGANIC
      CONSTITUENTS OF BARLEY PLANTS.

PMID- 16653785
TI  - WEEKLY ABSORPTION OF NITRATE BY YOUNG, BEARING ORANGE TREES GROWING OUT OF DOORS
      IN SOLUTION CULTURES.

PMID- 16653786
TI  - SOME EFFECTS OF RADIANT ENERGY IN RELATION TO ETIOLATION.

PMID- 16653787
TI  - THE CULTURE OF ALBINO MAIZE.

PMID- 16653788
TI  - ABSORPTION AND ACCUMULATION OF RUBIDIUM BROMIDE BY BARLEY PLANTS. LOCALIZATION IN
      THE ROOT OF CATION ACCUMULATION AND OF TRANSFER TO THE SHOOT.

PMID- 16653789
TI  - SULPHUR CONTENT OF SEEDS AND SEED WEIGHT IN RELATION TO EFFECTS OF SULPHUR
      DEFICIENCY ON GROWTH OF SUNFLOWER PLANTS.

PMID- 16653790
TI  - EFFECT OF ORCHARD FERTILIZER APPLICATIONS ON THE COMPOSITION OF APPLES.

PMID- 16653791
TI  - PHOSPHORUS ANALYSIS OF PLANT MATERIAL.

PMID- 16653792
TI  - ROOT MODIFICATIONS INDUCED IN ZEA MAYS SEEDLINGS BY IRRADIATING DRY SEEDS WITH
      SOFT X-RAYS.

PMID- 16653793
TI  - EFFECT OF POTASSIUM IODIDE ON THE ASCORBIC ACID CONTENT AND GROWTH OF TOMATO
      PLANTS.

PMID- 16653795
TI  - RESPIRATION AND CHEMICAL CHANGES OF THE PAPAYA FRUIT IN RELATION TO TEMPERATURE.

PMID- 16653794
TI  - PRELIMINARY INVESTIGATION OF THE RHYTHMIC FLUCTUATIONS IN TRANSPIRATION UNDER
      CONSTANT ENVIRONMENTAL CONDITIONS.

PMID- 16653796
TI  - EFFECT OF DROUGHT ON THE PRODUCTION OF PLANT PIGMENTS.

PMID- 16653797
TI  - A GRATING SPECTROGRAPH FOR MINERAL NUTRITION STUDIES.

PMID- 16653798
TI  - AN ATMOSPHERIC HALATOMETER.

PMID- 16653800
TI  - NOTES.

PMID- 16653799
TI  - EFFECT OF INFECTING CARROT PLANTS WITH CERTAIN VIRUSES ON SEEDSTALK DEVELOPMENT.

PMID- 16653801
TI  - A METHOD OF STUDYING THE MOVEMENT OF RESPIRATORY GASES THROUGH WAXY COATINGS.

PMID- 16653802
TI  - HYDROGEN ION CONCENTRATION IN RELATION TO ABSORPTION OF INORGANIC NUTRIENTS BY
      HIGHER PLANTS.

PMID- 16653803
TI  - INFLUENCE OF HYDROGEN ION CONCENTRATION ON THE GROWTH OF HIGHER PLANTS UNDER
      CONTROLLED CONDITIONS.

PMID- 16653804
TI  - CARBOHYDRATE AND NITROGEN TRENDS IN BLUEBUNCH WHEATGRASS, AGROPYRON SPICATUM,
      WITH SPECIAL REFERENCE TO GRAZING INFLUENCES.

PMID- 16653805
TI  - THE PROXIMATE CHEMICAL CONSTITUTENTS OF CITRUS WOODS, WITH SPECIAL REFERENCE TO
      LIGNIN.

PMID- 16653806
TI  - THE IRON-MANGANESE RELATION IN PLANT METABOLISM.

PMID- 16653807
TI  - INFLUENCE OF SUBMERSION OF THE ROOTS ON TRANSPIRATION, APPARENT PHOTOSYNTHESIS,
      AND RESPIRATION OF YOUNG APPLE TREES.

PMID- 16653808
TI  - GROWTH RATES OF MAIZE UNDER FIELD CONDITIONS.

PMID- 16653809
TI  - GROWTH RESPONSES OF BARLEY SEEDLINGS IN RELATION TO POTASSIUM AND SODIUM
      NUTRITION.

PMID- 16653810
TI  - COMPARISON OF THE EFFICIENCY OF SINGLE APPLICATIONS WITH REPEATED TOP DRESSINGS
      OF NITROGENOUS FERTILIZERS IN INCREASING THE YIELD OF DRY MATTER, NITROGEN, AND
      VITAMIN C (ASCORBIC ACID) OF SUDAN GRASS.

PMID- 16653811
TI  - THE AMOUNT OF BORON ABSORBED BY SOYBEAN PLANTS AND ITS EFFECT ON THEIR GROWTH.

PMID- 16653813
TI  - INTERLABORATORY COMPARISON OF ABSORPTION SPECTRA BY THE PHOTOELECTRIC
      SPECTROPHOTOMETRIC METHOD.-DETERMINATIONS ON CHLOROPHYLL AND WEIGERT'S SOLUTIONS.

PMID- 16653812
TI  - COMPARISON OF THE CALCIUM AND SULPHUR CONTENT OF PLANT FLUIDS EXPRESSED FROM
      TISSUES KILLED BY AUTOCLAVING AND BY FREEZING WITH SOLID CARBON DIOXIDE.

PMID- 16653814
TI  - INFLUENCE OF SULFANILAMIDE AND DERIVATIVES ON GROWTH OF LUPINUS ALBUS.

PMID- 16653815
TI  - A COMPARISON OF THE EFFECTS OF GREEN LIGHT AND OF RED LIGHT ON THE SIMPLE-LEAF
      DEVELOPMENT OF INTACT AND DECAPITATED BEAN PLANTS.

PMID- 16653816
TI  - THE MECHANISM OF AUXIN ACTION.

PMID- 16653817
TI  - ENZYMES AND THE LAW OF MASS ACTION.

PMID- 16653818
TI  - AERIAL ROOTS FROM OLD TREE WOUND.

PMID- 16653819
TI  - NOTES.

PMID- 16653820
TI  - THE PROCESS OF OIL FORMATION AND ACCUMULATION IN THE MACADAMIA.

PMID- 16653821
TI  - OXIDATION-REDUCTION POTENTIALS OF THE TISSUE FLUID OF CABBAGE.

PMID- 16653822
TI  - THE USE OF ION EXCHANGE MATERIALS IN STUDIES ON CORN NUTRITION.

PMID- 16653823
TI  - ESTIMATION OF STOMATED FOLIAR SURFACE OF PINES.

PMID- 16653824
TI  - BRIEF PAPERS: A TECHNIQUE FOR TREATING SMALL SEEDLINGS WITH COLCHICINE.

PMID- 16653825
TI  - A SIMPLIFIED INTEGRATING LIGHT RECORDER FOR FIELD USE.

PMID- 16653826
TI  - A LIGHT-TIGHT BOX FOR MAKING SHADOWGRAPHS OF AVENA SEEDLINGS FOR GROWTH HORMONE
      DETERMINATIONS.

PMID- 16653827
TI  - NOTES.

PMID- 16653829
TI  - EFFECTS OF CERTAIN GROWTH REGULATING SUBSTANCES ON GROWTH CORRELATION IN LETTUCE
      SEEDLINGS.

PMID- 16653828
TI  - EFFECTS OF DROUGHT, TEMPERATURE AND NITROGEN ON TURF GRASSES.

PMID- 16653830
TI  - EFFECT OF THE ROOT SYSTEM ON TOMATO STEM GROWTH.

PMID- 16653831
TI  - USE OF TENSIOMETERS IN MEASURING AVAILABILITY OF WATER TO PLANTS.

PMID- 16653832
TI  - MEASUREMENT OF SMALL CONCENTRATIONS OF ETHYLENE AND AUTOMOBILE EXHAUST GASES AND
      THEIR RELATION TO LEMON STORAGE.

PMID- 16653833
TI  - STIMULATIVE EFFECTS OF X-RAYS ON PLANTS.

PMID- 16653834
TI  - RESPIRATION OF MOSAIC-INFECTED TOBACCO PLANTS.

PMID- 16653835
TI  - RIDGES AND SECTORS INDUCED IN THE RIND OF CITRUS FRUITS BY FUMIGATION WTH
      HYDROCYANIC ACID.

PMID- 16653836
TI  - A SYSTEM OF ANALYSIS FOR PLANT TISSUE BY USE OF PLANT JUICE.

PMID- 16653838
TI  - AMOUNT, DISTRIBUTION, AND SEASONAL TREND OF CERTAIN ORGANIC RESERVES IN THE ROOT
      SYSTEM OF FIELD BINDWEED, CONVOLVULUS ARVENSIS L.

PMID- 16653837
TI  - EFFECT OF SALT CONCENTRATION, KIND OF SALT, AND CLIMATE ON PLANT GROWTH IN SAND
      CULTURES.

PMID- 16653839
TI  - SOLUBLE CONSTITUENTS AND BUFFER PROPERTIES OF ORANGE JUICE.

PMID- 16653840
TI  - MOLECULAR EQUIVALENCE OF CARBOHYDRATES TO CARBON DIOXIDE IN PHOTOSYNTHESIS.

PMID- 16653841
TI  - ROLE OF ETHER SOLUBLE ORGANIC ACIDS IN THE CATIONANION BALANCE IN PLANTS.

PMID- 16653842
TI  - AMOUNT AND DURATION OF GROWTH OF VARIOUS SPECIES OF TREE SEEDLINGS.

PMID- 16653843
TI  - TRANSPIRATION RATES OF SOME FOREST TREE SPECIES DURING THE DORMANT SEASON.

PMID- 16653844
TI  - A NOTE ON THE GROWTH BEHAVIOR OF COTTON BOLLS.

PMID- 16653845
TI  - POLLEN GERMINATION AND POLLEN TUBE GROWTH, AS INFLUENCED BY PURE GROWTH
      SUBSTANCES.

PMID- 16653846
TI  - AN AUTO-IRRIGATOR FOR GROWING PLANTS IN THE LABORATORY.

PMID- 16653847
TI  - A METHOD OF INCREASING THE RATE OF SEED GERMINATION OF TARAXACUM KOK-SAGHYZ.

PMID- 16653848
TI  - INHIBITING INFLUENCE OF THE LEAVES ON THE PHOTOPERIODIC RESPONSE OF NOBLE
      SPINACH.

PMID- 16653850
TI  - BRIEF PAPERS: CHLOROSIS IN SUDAN GRASS.

PMID- 16653849
TI  - THE AMERICAN MISLETOE WITH RESPECT TO CHLOROPHYLL AND PHOTOSYNTHESIS.

PMID- 16653851
TI  - ENZYME ACTION DOMINATED BY ASSOCIATED COLLOIDS.

PMID- 16653852
TI  - A POSSIBLE NON-ENZYMATIC MECHANISM OF CHANGES OCCURRING IN THE PECTIC SUBSTANCES
      AND OTHER POLYSACCHARIDES IN LIVING PLANTS.

PMID- 16653854
TI  - NOTES.

PMID- 16653853
TI  - AN AIR PUMP OF LOW CAPACITY.

PMID- 16653855
TI  - FOOD RESERVE DEPLETION AND SYNTHESIS IN FIELD BINDWEED, CONVOLVULUS ARVENSIS L.,
      AS RELATED TO 7-DAY AND 14-DAY INTERVALS OF CULTIVATION.

PMID- 16653856
TI  - NUTRIENT DEFICIENCIES IN THE STRAWBERRY LEAF AND FRUIT.

PMID- 16653857
TI  - AN INSTALLATION OF LARGE SAND-CULTURE BEDS SURMOUNTED BY INDIVIDUAL AIR
      CONDITIONED GREENHOUSES.

PMID- 16653858
TI  - THE UTILIZATION OF SULPHATE AND SULPHUR DIOXIDE FOR THE SULPHUR NUTRITION OF
      ALFALFA.

PMID- 16653859
TI  - POLARIZATION AND STIMULATION OF THE ONION ROOT BY DIRECT CURRENT.

PMID- 16653860
TI  - PREPARATION OF SYNTHETIC COMPOSTS FOR MUSHROOM CULTURE.

PMID- 16653861
TI  - EFFECT OF BORON IN THE SUBSTRATE ON THE RATE OF NITRATE ABSORPTION AND ON
      NITROGEN DISTRIBUTION IN NASTURTIUM.

PMID- 16653862
TI  - CHANGES IN CERTAIN WATER-SOLUBLE NITROGENOUS CONSTITUENTS OF BURLEY TOBACCO
      DURING CURING.

PMID- 16653863
TI  - A QUANTITATIVE STUDY OF CHLOROSIS IN CHLORELLA UNDER CONDITIONS OF SULPHUR
      DEFICIENCY.

PMID- 16653864
TI  - STRUCTURE AND COMPOSITION OF CITRUS LEAVES AFFECTED WITH MESOPHYLL COLLAPSE.

PMID- 16653865
TI  - RADIANT ENERGY NOMENCLATURE.

PMID- 16653866
TI  - SUGARS IN RELATION TO COLOR AND THIOCYANATE SPRAY IN APPLES.

PMID- 16653867
TI  - INFLUENCE OF UNKNOWN FACTORS ON THE VALIDITY OF MATHEMATICAL CORRELATIONS OF
      BIOLOGICAL DATA.

PMID- 16653868
TI  - BORDEAUX INJURY TO FOLIAGE AT LOW TEMPERATURES.

PMID- 16653869
TI  - NUTRITIONAL RELATIONSHIPS OF BORON AND INDOLEACETIC ACID IN HEAD LETTUCE.

PMID- 16653870
TI  - GERMINATION (EMERGENCE) OF VEGETABLE SEED AS AFFECTED BY DIFFERENT SOIL MOISTURE
      CONDITIONS.

PMID- 16653871
TI  - INFLUENCE OF THE HYDROGEN-ION CONCENTRATION OF THE SUBSTRATE ON THE DEVELOPMENT
      OF LEAFY MOSS PLANTS.

PMID- 16653873
TI  - NOTES.

PMID- 16653872
TI  - BRIEF PAPER: BLOSSOM INDUCTION OF THE CRANBERRY.

PMID- 16653874
TI  - A NEW TYPE OF INTERMITTENTLY-IRRIGATED SAND CULTURE EQUIPMENT.

PMID- 16653875
TI  - A BIOCHEMICAL STUDY OF CURING PROCESSES IN SWEET POTATOES.

PMID- 16653876
TI  - SOME EFFECTS OF SODIUM SALTS ON THE GROWTH OF THE TOMATO.

PMID- 16653877
TI  - STIMULATION OF THE ONION ROOT BY ALTERNATING CURRENT.

PMID- 16653878
TI  - QUANTITATIVE MEASUREMENT OF THE VELOCITY OF WATER ABSORPTION IN INDIVIDUAL ROOT
      HAIRS BY A MICROTECHNIQUE.

PMID- 16653879
TI  - EFFECTS OF IRON ON THE GROWTH AND ASH CONSTITUENTS OF ANANAS COMOSUS (L.) MERR.

PMID- 16653880
TI  - FLAGELLATES OF LATICIFEROUS PLANTS.

PMID- 16653882
TI  - EFFECT OF OXYGEN CONCENTRATION ON THE RESPIRATION OF SOME VEGETABLES.

PMID- 16653881
TI  - COMPOSITION OF THE ROOTS AND STUBBLE OF PERENNIAL RYEGRASS FOLLOWING PARTIAL
      DEFOLIATION.

PMID- 16653884
TI  - FIRMNESS OF STRAWBERRIES AS MEASURED BY A PENETROMETER.

PMID- 16653883
TI  - GERMINATION, GROWTH, AND RESPIRATION OF RICE AND BARLEY SEEDLINGS AT LOW OXYGEN
      PRESSURES.

PMID- 16653885
TI  - SPECTROGRAPHIC ANALYSIS OF PLANT ASH FOR SEVERAL ELEMENTS SIMULTANEOUSLY.

PMID- 16653886
TI  - DECOMPOSITION OF THE LEAVES OF SOME FOREST TREES UNDER FIELD CONDITIONS.

PMID- 16653887
TI  - INTERNAL PRECIPITATION OF PHOSPHORUS IN RELATION TO ALUMINUM TOXICITY.

PMID- 16653888
TI  - BRIEF PAPERS: PYRROLE DERIVATIVES AND IRON CHLOROSIS IN PLANTS.

PMID- 16653890
TI  - NOTES.

PMID- 16653889
TI  - LENGTHENING THE STORAGE LIFE OF APPLES BY REMOVAL OF VOLATILE MATERIALS FROM THE
      STORAGE ATMOSPHERE.

PMID- 16653891
TI  - THE EXUDATION OF GLUTAMINE FROM LAWN GRASS.

PMID- 16653892
TI  - EFFECT OF BORON, COPPER, MANGANESE, AND ZINC ON THE ENZYME ACTIVITY OF TOMATO AND
      ALFALFA PLANTS GROWN IN THE GREENHOUSE.

PMID- 16653893
TI  - RELATION OF LIGHT TO GROWTH OF PLANTS.

PMID- 16653894
TI  - FRUIT GROWTH AND FOOD TRANSPORT IN CUCURBITS.

PMID- 16653895
TI  - RELATION OF WEATHER CONDITIONS TO ONION BLAST.

PMID- 16653896
TI  - SEMI-MICRO ESTIMATION OF REDUCING SUGARS.

PMID- 16653897
TI  - USE OF ROOT PRESSURES IN DETERMINING INJURY TO ROOTS BY CULTIVATION.

PMID- 16653898
TI  - BUFFER VALUES OF THE LEAVES OF SOME PLANTS.

PMID- 16653899
TI  - GLASS POTOMETERS FOR STUDIES OF ABSORPTION AND EXUDATION BY EXCISED ROOTS.

PMID- 16653900
TI  - NOTES.

PMID- 16653901
TI  - ELECTRODIALYSIS OF SEEDS.

PMID- 16653902
TI  - EFFECTS OF OXYGEN TENSION ON CERTAIN PHYSIOLOGICAL RESPONSES OF RICE, BARLEY, AND
      TOMATO.

PMID- 16653903
TI  - EFFECTS OF IRON ON CHLOROPHYLLOUS PIGMENTS, ASCORBIC ACID, ACIDITY AND
      CARBOHYDRATES OF ANANAS COMOSUS (L.) MERR., SUPPLIED WITH NITRATE OR AMMONIUM
      SALTS.

PMID- 16653904
TI  - EFFECT OF INTERMITTENT IRRADIATION ON PHOTOPERIODIC RESPONSES.

PMID- 16653905
TI  - RAPID ANALYTICAL METHODS FOR SOME OF THE MORE COMMON INORGANIC CONSTITUENTS OF
      PLANT TISSUES.

PMID- 16653906
TI  - EVALUATION OF FOLIAGE INJURY AND WATER LOSS IN CONNECTION WITH USE OF WAX AND OIL
      EMULSIONS.

PMID- 16653907
TI  - APPARENT PHOTOSYNTHESIS IN SOME CONIFERS DURING WINTER.

PMID- 16653908
TI  - HAIR SPROUT OF POTATOES.

PMID- 16653909
TI  - RELATION BETWEEN ELECTRICAL AND CURVATURE RESPONSES IN THE AVENA COLEOPTILE TO
      MECHANICAL STIMULI.

PMID- 16653910
TI  - SOME CHEMICAL REACTIONS OF SULPHUR DIOXIDE AFTER ABSORPTION BY ALFALFA AND SUGAR
      BEETS.

PMID- 16653911
TI  - A STUDY OF THE SULPHUR METABOLISM OF WHEAT, BARLEY AND CORN USING RADIOACTIVE
      SULPHUR.

PMID- 16653912
TI  - RADIOAUTOGRAPHS SHOWING THE DISTRIBUTION OF SULPHUR IN WHEAT.

PMID- 16653913
TI  - IONIC ABSORPTION BY TOMATO PLANTS AS CORRELATED WITH VARIATIONS IN THE
      COMPOSITION OF THE NUTRIENT MEDIUM.

PMID- 16653914
TI  - ABSORPTION OF CARBON DIOXIDE BY MAIZE.

PMID- 16653915
TI  - GROWTH RESPONSES OF HEMP TO DIFFERENTIAL SOIL AND AIR TEMPERATURES.

PMID- 16653916
TI  - EFFECT OF MOISTURE AND OF TREATMENTS WITH ACID AND ALKALI ON RATE OF FORMATION OF
      FREE FATTY ACIDS IN STORED COTTONSEED.

PMID- 16653917
TI  - COMPOSITION OF FRUITS AND PHLOEM EXUDATE OF CUCURBITS.

PMID- 16653918
TI  - OSMOTIC QUANTITIES IN GROWING COTTON BOLLS.

PMID- 16653919
TI  - RELATION BETWEEN LIGHT INTENSITY AND RATE OF PHOTOSYNTHESIS OF LOBLOLLY PINE AND
      CERTAIN HARDWOODS.

PMID- 16653920
TI  - THE CULTIVATION OF CHLORELLA SP.

PMID- 16653921
TI  - APPARENT EQUILIBRIUM BETWEEN PHOTOSYNTHESIS AND RESPIRATION IN AN UNRENEWED
      ATMOSPHERE.

PMID- 16653922
TI  - CHEMICAL COMPOSITION OF ROOTS AND TOPS OF DIOECIOUS LYCHNIS IN VEGETATIVE AND
      FLOWERING PHASES OF GROWTH.

PMID- 16653923
TI  - THE HOTTENTOT FIG AS A POSSIBLE COMMERCIAL SOURCE OF TANNIN.

PMID- 16653924
TI  - NOTES.

PMID- 16653925
TI  - CONCURRENCY OF CARBOHYDRATE FORMATION AND CARBON DIOXIDE ABSORPTION DURING
      PHOTOSYNTHESIS IN SUNFLOWER LEAVES.

PMID- 16653926
TI  - SOME EFFECTS OF BORON SUPPLY ON THE CHEMICAL COMPOSITION OF TOMATO LEAFLETS.

PMID- 16653927
TI  - NUTRIENT INTERRELATIONS IN LIME-INDUCED CHLOROSIS.

PMID- 16653928
TI  - MYCORRHIZAL SYMBIOSIS IN APLECTRUM, CORALLORHIZA AND PINUS.

PMID- 16653929
TI  - CALCIUM AND OTHER POLYVALENT CATIONS AS ACCELERATORS OF ION ACCUMULATION BY
      EXCISED BARLEY ROOTS.

PMID- 16653930
TI  - THE GROWTH AND CARBOHYDRATE RESPONSES OF AGROPYRON SMITHII AND BOUTELOUA GRACILIS
      TO CHANGES IN NITROGEN SUPPLY.

PMID- 16653931
TI  - INFLUENCE OF PHOSPHORUS SUPPLY AND THE FORM OF AVAILABLE NITROGEN ON THE
      ABSORPTION AND THE DISTRIBUTION OF PHOSPHORUS BY THE TOMATO PLANT.

PMID- 16653932
TI  - SUGAR MOVEMENT TO ROOTS, MINERAL UPTAKE, AND THE GROWTH CYCLE OF THE COTTON
      PLANT.

PMID- 16653933
TI  - RELATION OF THE PRODUCTION OF AN ACTIVE EMANATION TO RESPIRATION IN THE AVOCADO
      FRUIT.

PMID- 16653934
TI  - PHYSICAL CHARACTERS OF THE SKIN IN RELATION TO APPLE FRUIT TRANSPIRATION.

PMID- 16653935
TI  - LIGHT AND THE ELONGATION OF THE MESOCOTYL IN CORN.

PMID- 16653937
TI  - IS NATURAL GAS INJURIOUS TO FLOWERING PLANTS?

PMID- 16653936
TI  - CRYOSCOPY OF SMALL AMOUNTS OF EXPRESSED TISSUE SAP.

PMID- 16653938
TI  - ISOLATION IN UNIALGAL CULTURE OF LICHEN GONIDIA BY A SIMPLE PLASMOLYSIS
      TECHNIQUE.

PMID- 16653939
TI  - USE OF MONOCHLORACETIC ACID TO INCLUDE AMMONIA IN THE "SOLUBLE NITROGEN" TISSUE
      TEST.

PMID- 16653940
TI  - NOTES.

PMID- 16653941
TI  - SIR JOHN RUSSELL.

PMID- 16653942
TI  - LIGHT AND PIGMENT DEVELOPMENT IN THE KIDNEY BEAN.

PMID- 16653943
TI  - THE GROWTH OF CHLORELLA PYRENOIDOSA UNDER VARIOUS CULTURE CONDITIONS.

PMID- 16653944
TI  - STUDIES ON MINERAL DEFICIENCY IN PINE.

PMID- 16653945
TI  - SUGARS IN APPLE AND CHERRY BLOSSOMS.

PMID- 16653946
TI  - THE CAROTENE AND ASCORBIC ACID CONCENTRATION OF VEGETABLE VARIETIES.

PMID- 16653947
TI  - SPECTROSCOPIC STABILITY OF CHLOROPHYLLS a AND b AND CERTAIN ANALYTICAL
      CONSIDERATIONS.

PMID- 16653948
TI  - EFFECT OF DAYLENGTH ON GROWTH AND REPRODUCTION OF THE CUCUMBER.

PMID- 16653949
TI  - INFLUENCE OF PHOSPHORUS SUPPLY AND THE FORM OF AVAILABLE NITROGEN ON THE NITROGEN
      METABOLISM OF THE TOMATO PLANT.

PMID- 16653950
TI  - THE EFFECT OF DISC THICKNESS ON THE RESPIRATION AND THE VARIOUS NITROGEN
      FRACTIONS OF CUT DISCS OF RADISH ROOTS IMMERSED IN WATER AND IN SUGAR SOLUTIONS.

PMID- 16653951
TI  - EFFECT OF NUTRIENT RATIO AND CONCENTRATION ON GROWTH AND COMPOSITION OF TOMATO
      PLANTS AND ON THE OCCURENCE OF BLOSSOM-END ROT OF THE FRUIT.

PMID- 16653952
TI  - EFFECT OF TEMPERATURE ON PHOTOSYNTHESIS AND RESPIRATION IN RED AND LOBLOLLY
      PINES.

PMID- 16653953
TI  - CHLOROPHYLL AND CAROTENE CONTENT OF EIGHTEEN TOBACCO VARIETIES.

PMID- 16653954
TI  - CHANGES IN CHEMICAL COMPOSITION OF TUNG KERNELS DURING GERMINATION.

PMID- 16653956
TI  - A SIMPLE APPARATUS FOR SAND CULTURE WORK.

PMID- 16653955
TI  - A METHOD FOR MEASURING ROOT RESPIRATION.

PMID- 16653957
TI  - EFFECT OF HEAVY APPLICATIONS OF GYPSUM ON PLANT GROWTH.

PMID- 16653958
TI  - NOTES.

PMID- 16653959
TI  - GROWTH AND BIOCHEMICAL COMPOSITION OF BEAN PLANTS AS CONDITIONED BY SOIL MOISTURE
      TENSION AND SALT CONCENTRATION.

PMID- 16653960
TI  - CHANGES IN ELECTRICAL POLARITY IN THE AVENA COLEOPTILE AS AN ANTECEDENT TO
      HORMONE ACTION IN GEOTROPIC RESPONSE.

PMID- 16653961
TI  - RENEWAL OF GROWTH BY GUAYULE TRANSPLANTS.

PMID- 16653962
TI  - A CRITICAL EVALUATION OF THE TERMINOLOGY OF DIFFUSION PHENOMENA.

PMID- 16653964
TI  - EFFECT OF FERTILIZERS ON LOBLOLLY PINE IN A NORTH CAROLINA NURSERY.

PMID- 16653963
TI  - NOTES.

PMID- 16653965
TI  - THE INFLUENCE OF HEPARIN ON GROWTH OF LUPINUS ALBUS SEEDLINGS.

PMID- 16653966
TI  - ANALYSIS OF THE ORGANIC ACIDS OF ORANGE JUICE.

PMID- 16653967
TI  - SIGNIFICANCE OF THE pH OF BLUEBERRY LEAVES.

PMID- 16653968
TI  - SOME ASPECTS OF THE METABOLISM OF THE EBENEZER ONION.

PMID- 16653969
TI  - SUGARS IN THE ROOT OF THE CARROT.

PMID- 16653970
TI  - LEAF ANALYSIS AS AN INDICATOR OF POTASSIUM REQUIREMENT OF CANE FRUITS.

PMID- 16653971
TI  - ABSORPTION OF HYDROCYANIC ACID BY VALENCIA-ORANGE FRUITS AND LEAVES FUMIGATED AT
      ATMOSPHERIC PRESSURE AND AT PARTIAL VACUUM.

PMID- 16653972
TI  - ASHING PROCEDURES FOR THE DETERMINATION OF COPPER IN PLANT MATERIAL.

PMID- 16653974
TI  - DIURNAL AND SEASONAL CHANGES IN THE ASCORBIC ACID CONTENT OF SOME VEGETABLES.

PMID- 16653973
TI  - PHOTOSYNTHESIS IN MAIZE AS INFLUENCED BY A TRANSPIRATION-REDUCING SPRAY.

PMID- 16653975
TI  - CHARLES ALBERT SHULL: AN APPRECIATION.

PMID- 16653976
TI  - RESPIRATION AND INTERNAL GAS CONTENT OF INJURED SWEET-POTATO ROOTS.

PMID- 16653977
TI  - GROWTH AND NUTRIENT RESPONSES OF LITTLE TURKISH TOBACCO TO LONG AND SHORT
      PHOTOPERIODS.

PMID- 16653978
TI  - TEMPERATURE-GROWTH RELATIONS OF THE ROOTS AND HYPOCOTYLS OF COTTON SEEDLINGS.

PMID- 16653979
TI  - EFFECT OF CARBON DIOXIDE ON ABSORPTION OF WATER AND NUTRIENTS BY ROOTS.

PMID- 16653980
TI  - IRON IN THE LEAVES AND CHLOROPLASTS OF SOME PLANTS IN RELATION TO THEIR
      CHLOROPHYLL CONTENT.

PMID- 16653981
TI  - THE EFFECT OF REDUCED LIGHT INTENSITY ON THE AERIAL AND SUBTERRANEAN PARTS OF THE
      EUROPEAN BINDWEED.

PMID- 16653982
TI  - A SIMPLIFIED RECORDING POTENTIOMETER.

PMID- 16653983
TI  - SOME EFFECTS OF BORON AND MANGANESE ON THE QUALITY OF BEETS AND TOMATOES.

PMID- 16653984
TI  - THE B VITAMIN CONTENT OF BUDS AND SHOOTS OF SOME COMMON TREES.

PMID- 16653985
TI  - EFFECT OF COPPER AND ZINC DEFICIENCIES ON THE PHOTOSYNTHETIC ACTIVITY OF OF THE
      FOLIAGE OF YOUNG TUNG TREES.

PMID- 16653986
TI  - A GERMINATION INHIBITOR IN THE SEED COATS OF CERTAIN VARIETIES OF CABBAGE.

PMID- 16653987
TI  - A SIMPLE AND INEXPENSIVE VOLTAGE REGULATOR FOR LABORATORY USE.

PMID- 16653988
TI  - VITAMIN CONTENT OF SOME MATURE AND GERMINATED LEGUME SEEDS.

PMID- 16653989
TI  - THE USE OF MONOCHLORACETIC ACID TO INCLUDE AMMONIA IN THE CHLORATE METHOD FOR
      TOTAL NITROGEN IN PLANT TISSUE.

PMID- 16653990
TI  - ALUMINUM TOXICITY: MICROCHEMICAL TESTS FOR INORGANICALLY AND ORGANICALLY BOUND
      PHOSPHORUS.

PMID- 16653991
TI  - PRE-STORAGE CARBON DIOXIDE TREATMENTS FOR CONTROL OF APPLE SCALD.

PMID- 16653992
TI  - NOTES.

PMID- 16653993
TI  - BORON IN CITRUS TREES.

PMID- 16653995
TI  - EXTENT AND LONGEVITY OF THE SEMINAL ROOTS OF CERTAIN GRASSES.

PMID- 16653994
TI  - EFFECT OF MECHANICAL STIMULATION ON THE ELECTRICAL AND CURVATURE RESPONSES IN THE
      AVENA COLEOPTILE.

PMID- 16653996
TI  - EFFECT OF LIGHT INTENSITY, NITROGEN SUPPLY, AND FRUITING ON CARBOHYDRATE
      UTILIZATION BY THE COTTON PLANT.

PMID- 16653998
TI  - INDUCING DORMANCY IN LETTUCE SEED WITH COUMARIN.

PMID- 16653997
TI  - STARCH AND SUGARS OF VITIS VINIFERA.

PMID- 16653999
TI  - A SIMPLE AND EFFECTIVE HUMIDITY CONTROL.

PMID- 16654000
TI  - THE RESPIRATION OF GROWING PLANT CELLS.

PMID- 16654001
TI  - NOTE ON GALL FORMATION IN DECAPITATED YOUNG BEAN PLANTS.

PMID- 16654002
TI  - WOUNDING AND SUGAR TRANSLOCATION.

PMID- 16654003
TI  - A NOTE ON THE PRESENCE OF PYRUVIC ACID IN EBENEZER ONIONS.

PMID- 16654004
TI  - NOTES.

PMID- 16654006
TI  - BREAKING THE DORMANCY OF PEACH SEED BY TREATMENT WITH THIOUREA.

PMID- 16654005
TI  - RESPIRATORY ACTIVITY AND DURATION OF LIFE OF APPLES GATHERED AT DIFFERENT STAGES
      OF DEVELOPMENT AND SUBSEQUENTLY MAINTAINED AT A CONSTANT TEMPERATURE.

PMID- 16654007
TI  - PERMANENT WILTING PERCENTAGES OF SOILS OBTAINED FROM FIELD AND LABORATORY TRIALS.

PMID- 16654008
TI  - THE INFLUENCE OF MINERAL NUTRITION, SOIL FERTILITY, AND CLIMATE ON CAROTENE AND
      ASCORBIC ACID CONTENT OF TURNIP GREENS.

PMID- 16654010
TI  - A DIBASAL (MINIMUM SALT, MAXIMUM YIELD) SOLUTION FOR ASPERGILLUS NIGER; ACIDITY
      AND MAGNESIUM OPTIMUM.

PMID- 16654009
TI  - DROUGHT RESISTANCE IN RANGE AND PASTURE GRASSES.

PMID- 16654012
TI  - QUANTITATIVE STUDY OF ETHYLENE PRODUCTION IN APPLE VARIETIES.

PMID- 16654011
TI  - EFFECTS OF DIFFERENT AMOUNTS OF POTASSIUM ON GROWTH AND ASH CONSTITUENTS OF
      ANANAS COMOSUS (L.) MERR.

PMID- 16654013
TI  - OBSERVATIONS ON THE CAUSES OF THE FLOW OF SAP IN RED MAPLE.

PMID- 16654014
TI  - EFFECTS OF POTASSIUM ON CHLOROPHYLL, ACIDITY, ASCORBIC ACID, AND CARBOHYDRATES OF
      ANANAS COMOSUS (L.) MERR.

PMID- 16654015
TI  - WATER RELATIONS OF POCOSIN OR BOG SHRUBS.

PMID- 16654016
TI  - A NOTE ON THE EFFECTS OF COPPER IMPURITIES IN DISTILLED WATER ON GROWTH OF
      PLANTS.

PMID- 16654017
TI  - NOTES.

PMID- 16654019
TI  - AN ELECTROMETRIC METHOD FOR DEFINING THE AREA OF BARK AFFECTED BY TAPPING HEVEA
      BRASILIENSIS.

PMID- 16654018
TI  - CRITERIA OF NUTRITIVE RELATIONS OF FUNGI AND SEED-PLANTS IN MYCORRHIZAE.

PMID- 16654020
TI  - ENTRANCE OF WATER INTO SUBERIZED ROOTS OF TREES.

PMID- 16654021
TI  - GROWTH STIMULATION AND PHOSPHORUS ABSORPTION OF MYCORRHIZAL AND NON-MYCORRHIZAL
      NORTHERN WHITE PINE AND DOUGLAS FIR SEEDLINGS IN RELATION TO FERTILIZER
      TREATMENT.

PMID- 16654022
TI  - NOTES.

PMID- 16654023
TI  - EFFECT OF VARIOUS OXYGEN AND CARBON DIOXIDE CONCENTRATIONS ON COTTON ROOT
      DEVELOPMENT.

PMID- 16654024
TI  - ABSORPTION OF WATER THROUGH SUBERIZED ROOTS OF TREES.

PMID- 16654025
TI  - MINERAL REQUIREMENTS OF LEMNA MINOR.

PMID- 16654027
TI  - THE LACK OF SCION EFFECT ON ROOT QUALITY OF DERRIS ELLIPTICA.

PMID- 16654026
TI  - INFLUENCE OF EXTERNAL AND INTERNAL FACTORS ON GROWTH HORMONE IN GREEN PLANTS.

PMID- 16654028
TI  - EFFECT OF AUXINS ON THE ACTION OF DIASTASE IN VITRO.

PMID- 16654029
TI  - EFFECTS OF IRON ON CERTAIN NITROGENOUS FRACTIONS OF ANANAS COMOSUS (L.) MERR.

PMID- 16654030
TI  - TRANSPIRATION OF PINE SEEDLINGS AS INFLUENCED BY FOLIAGE COATINGS.

PMID- 16654031
TI  - DEVELOPMENT OF SOME RECENT CONCEPTS IN THE PHYSIOLOGICAL CHEMISTRY OF THE TOBACCO
      ALKALOIDS.

PMID- 16654032
TI  - NEW CARRIERS FOR PLANT GROWTH REGULATORS.

PMID- 16654033
TI  - THE ORGANIC ACIDS OF GRAPEFRUIT JUICE.

PMID- 16654034
TI  - EFFECTS OF VARIOUS AGENTS ON THE STRUCTURAL VISCOSITY OF ELODEA PROTOPLASM.

PMID- 16654035
TI  - THE SOLUBLE NITROGEN FRACTIONS OF POTATO TUBERS; THE AMIDES.

PMID- 16654036
TI  - THE EFFECT OF VARIOUS IONS ON GUTTATION OF THE TOMATO.

PMID- 16654037
TI  - LENGTH OF LIFE OF ROOTS OF TEN SPECIES OF PERENNIAL RANGE AND PASTURE GRASSES.

PMID- 16654038
TI  - EFFECTS OF POTASSIUM ON THE NITROGENOUS CONSTITUENTS OF ANANAS COMOSUS (L.) MERR.

PMID- 16654039
TI  - PHYCOMYCES IN THE ASSAY OF THIAMINE IN AGAR.

PMID- 16654041
TI  - NOTES.

PMID- 16654040
TI  - LEAFSPOT OF PEANUT ASSOCIATED WITH MAGNESIUM DEFICIENCY.

PMID- 16654042
TI  - EFFECTS OF NITROGEN ON GROWTH AND ASH CONSTITUENTS OF ANANAS COMOSUS (L.) MERR.

PMID- 16654043
TI  - NITROGEN METABOLISM OF CORN (ZEA MAYS) AS INFLUENCED BY AMMONIUM NUTRITION.

PMID- 16654044
TI  - THE EFFECT OF COPPER DEFICIENCY ON THE NITROGEN METABOLISM AND OIL SYNTHESIS OF
      THE TUNG TREE.

PMID- 16654045
TI  - EFFECT OF OXYGEN AND SODIUM THIOGYCOLLATE ON GROWTH OF RICE.

PMID- 16654046
TI  - FACTORS INFLUENCING THE VOLATILE OIL CONTENT OF THE PEEL OF IMMATURE AND MATURE
      ORANGES.

PMID- 16654047
TI  - THE EFFECT OF TOP ENVIRONMENT AND FLOWERING UPON TOP-ROOT RATIOS.

PMID- 16654048
TI  - SELECTIVITY OF HERBICIDES.

PMID- 16654049
TI  - NOTE ON THE EFFECT OF UNILATERAL ILLUMINATION ON THE TRANSVERSE ELECTRICAL
      POLARITY IN THE AVENA COLEOPTILE.

PMID- 16654050
TI  - THE EFFECTS OF AN INCREASE IN PRESSURE ON THE ACTION OF DIASTASE IN VITRO.

PMID- 16654052
TI  - NOTES.

PMID- 16654051
TI  - RIDGES AND SECTORS INDUCED IN OLIVE FRUITS BY FUMIGATION WITH HYDROCYANIC ACID.

PMID- 16654053
TI  - THE CASE FOR GREATER COOPERATION AMONG THE PLANT SCIENCE SOCIETIES.

PMID- 16654054
TI  - THE COMING OF AGE OF THE AMERICAN SOCIETY OF PLANT PHYSIOLOGISTS.

PMID- 16654055
TI  - PHOTOCHEMICAL REDUCTION OF CHLOROPLAST GRANA.

PMID- 16654056
TI  - AN APPARATUS AND METHOD FOR THE MEASUREMENT OF THE RESPIRATION OF COTTONSEED.

PMID- 16654057
TI  - THE RESPIRATORY PROCESSES IN PLANT CELLS IN RELATION TO THE FORMATION OF
      COACERVATES.

PMID- 16654058
TI  - CONCERNING THE FUNCTION OF RUBBER HYDROCARBON (CAOUTCHOUC) IN THE GUAYULE PLANT,
      PARTHENIUM ARGENTATUM A. GRAY.

PMID- 16654059
TI  - THE EXTENSION OF PLANT ROOTS INTO DRY SOIL.

PMID- 16654060
TI  - THE EFFECTS OF LIGHT, GRAVITY, AND CENTRIFUGAL FORCE UPON THE TROPIC RESPONSES OF
      BUCKWHEAT SEEDLINGS.

PMID- 16654061
TI  - MICROMANIPULATIVE STUDIES ON GELATINIZED STARCH GRANULES.

PMID- 16654062
TI  - THE EFFECT OF LIGHT ON THE ELECTRICAL POLARITY AND THE RATE OF ELONGATION OF THE
      AVENA COLEOPTILE.

PMID- 16654063
TI  - SOME PHYSICAL AND CHEMICAL CHANGES IN THE COMPOSITION OF PECAN NUTS DURING KERNEL
      FILLING.

PMID- 16654064
TI  - SOME CHEMICAL CHANGES ASSOCIATED WITH THE TRANSITION FROM VEGETATIVE TO
      REPRODUCTIVE GROWTH OF WINTER WHEAT.

PMID- 16654065
TI  - RESPIRATION OF COTTONSEED.

PMID- 16654066
TI  - STABILITY OF THE BUFFER SYSTEM OF LEMON JUICE.

PMID- 16654067
TI  - CHANGES IN THE COMPOSITION OF SQUASH DURING STORAGE.

PMID- 16654068
TI  - POLAR DISTRIBUTION OF RESPIRATORY RATE IN THE ONION ROOT TIP.

PMID- 16654069
TI  - COMPARISON OF RESPIRATION, FREE FATTY ACID FORMATION, AND CHANGES IN THE SPECTRUM
      OF THE SEED OIL DURING THE STORAGE OF COTTONSEED.

PMID- 16654070
TI  - OSMOTIC PRESSURE DETERMINATIONS WITH ISOLATED PROTOPLASMIC PROTEINS.

PMID- 16654071
TI  - EFFECT OF INHIBITORS ON THE RESPIRATION AND STORAGE OF COTTONSEED.

PMID- 16654072
TI  - EFFECT OF 2,4-DICHLOROPHENOXY ACETIC ACID ON THE RIPENING OF BARTLETT PEARS.

PMID- 16654073
TI  - NOTES.

PMID- 16654074
TI  - Studies in the Metabolism of Crassulacean Plants: Changes in the Composition of
      Bryophyllum calycinum During Growth.

PMID- 16654075
TI  - Some Mold-Induced Changes in Shelled Corn.

PMID- 16654076
TI  - Changes in the Chlorophyll and Carotene Contents of Curing Burley Tobacco Cut at
      Different Stages of Maturity.

PMID- 16654077
TI  - Influence of Temperature on Growth and Alkaloid Content of Cinchona Seedlings.

PMID- 16654078
TI  - A Comparison of Photosynthesis in Individual Pine Needles and Entire Seedlings at
      Various Light Intensities.

PMID- 16654079
TI  - Changes in Food Reserves and Respiratory Capacity of Bindweed Tissues
      Accompanying Herbicidal Action of 2,4-Dichlorophenoxyacetic Acid.

PMID- 16654080
TI  - Studies on the Relationship between the Rate of Infection of Cotton Seedlings by
      Phymatotrichum omnivorum and the Available Oxygen Supply.

PMID- 16654081
TI  - Levulins and Inulin in Guayule, Parthenium argentatum A. Gray.

PMID- 16654082
TI  - An Automatic Apparatus to Cover and Uncover Plants in Photoperiod Experiments.

PMID- 16654083
TI  - Notes.

PMID- 16654084
TI  - The Vitamin Content of Soybeans and Soybean Sprouts as a Function of Germination
      Time.

PMID- 16654085
TI  - Effects of Nitrogen on the Nitrogenous Fractions of Ananas comosus (L.) Merr.

PMID- 16654086
TI  - The Use of 2,3,5-Triphenyl-Tetrazoliumchloride as a Measure of Seed
      Germinability.

PMID- 16654087
TI  - Chlorophyll and Protein Interrelationships in Ananas comosus (L.) Merr.

PMID- 16654088
TI  - Radioactive Phosphorus Procedures as Applied to Soil and Plant Research.

PMID- 16654089
TI  - Relations Between Carbohydrate Accumulation and Resistance of Cotton Plants to
      Phymatotrichum Root Rot in Dry Summers.

PMID- 16654090
TI  - Inverse Correlation Between Rubber Hydrocarbons and Insolubles in Total Solids of
      Latex from Hevea brasiliensis.

PMID- 16654091
TI  - The Formation of Chlorophyll A in Etiolated Oat Seedlings.

PMID- 16654092
TI  - Notes.

PMID- 16654093
TI  - Effects of Nitrogen on Chlorophyll, Acidity, Ascorbic Acid, and Carbohydrate
      Fractions of Ananas comosus (L.) Merr.

PMID- 16654094
TI  - Studies in the Metabolism of Crassulacean Plants; The Effect upon the Composition
      of Bryophyllum calycinum of the Form in which Nitrogen is Supplied.

PMID- 16654095
TI  - Effect of Mineral Deficiencies upon the Synthesis of Riboflavin and Ascorbic Acid
      by the Oat Plant.

PMID- 16654096
TI  - Interrelationships of Calcium, Nitrogen, and Phosphorus in Vegetable Crops.

PMID- 16654097
TI  - Ether-Soluble Organic Acids of Mature Valencia Orange Leaves.

PMID- 16654098
TI  - Starch Hydrolysis Induced by Polarized Light in Stomatal Guard Cells of Living
      Plants.

PMID- 16654099
TI  - Determination of Total Available Carbohydrates in Plants.

PMID- 16654100
TI  - Influence of Mineral Deficiencies on Growth and Composition of Vanilla Vines.

PMID- 16654101
TI  - The Effect of Indole-3-Acetic Acid in the Diastase Charcoal Model System.

PMID- 16654102
TI  - Influence of Phosphate on Stability of Crude Penicillin.

PMID- 16654103
TI  - A Viewpoint for Plant Physiology.

PMID- 16654105
TI  - The Chemical Relation of the Leaf, Sheath, and Stem of Blue Panicum, Panicum
      antidotale Retz.

PMID- 16654104
TI  - The Non-Flowering Character of Sweet Potatoes of the Jersey Type.

PMID- 16654106
TI  - A Modification of the Celluloid Holder for Cobalt Chloride Paper.

PMID- 16654108
TI  - Distribution of Rubber and Resins in Guayule.

PMID- 16654107
TI  - Notes.

PMID- 16654109
TI  - Studies in the Metabolism of Crassulacean Plants: The Diurnal Variation in
      Organic Acid and Starch Content of Bryophyllum calycinum.

PMID- 16654110
TI  - The Physiological Action of 2,4-Dichlorophenoxyacetic Acid on Dandelion,
      Taraxacum officinale.

PMID- 16654111
TI  - Growth of the Dandelion Scape.

PMID- 16654112
TI  - Some Effects of Temperature and Photoperiod on Flower Formation and Runner
      Production in the Strawberry.

PMID- 16654113
TI  - Carotenoid Pigments in Tubers of the Katahdin Variety of Irish Potato.

PMID- 16654114
TI  - The Sugars of the Roots of Daucus carota.

PMID- 16654115
TI  - Respiration and Nitrogen Metabolism of Whole and Sliced Radish Roots with
      Reference to the Effect of Alternation of Air and Nitrogen Atmospheres.

PMID- 16654116
TI  - Nitrogen Metabolism of Detached Corn Leaves in Darkness and in Light.

PMID- 16654117
TI  - Studies in the Metabolism of Crassulacean Plants: The Behavior of Excised Leaves
      of Bryophyllum calycinum During Culture in Water.

PMID- 16654118
TI  - Plant Growth with Artificial Sources of Radiant Energy.

PMID- 16654119
TI  - The Thermodynamics of Active (Non-osmotic) Water Absorption.

PMID- 16654120
TI  - Effect of Alternating Conditions of Boron Nutrition upon Growth and Boron Content
      of Grape Vines in Sand Culture.

PMID- 16654121
TI  - Some Effects of Potassium Deficiency on the Nitrogen Metabolism and Oil Synthesis
      in the Tung Tree (Aleurites Fordii).

PMID- 16654122
TI  - Vitamin Studies of Varieties and Strains of Peas.

PMID- 16654123
TI  - The Effect of Air Supply on Apparent Photosynthesis.

PMID- 16654124
TI  - Artificial Parthenocarpy in Lycopersicum esculentum; Tissue Development.

PMID- 16654125
TI  - The Porometer Method for the Continuous Estimation of Dimensions of Stomates.

PMID- 16654126
TI  - Culture Conditions and the Development of the Photosynthetic Mechanism: V.
      Influence of the Composition of the Nurient Medium.

PMID- 16654127
TI  - A Further Investigation of the Replacement of Boron by Indoleacetic Acid.

PMID- 16654128
TI  - Germination of Asystasia gangetica L. Seed with Special Reference to the Effect
      of Age on the Temperature Requirement for Germination.

PMID- 16654129
TI  - The Effect of Ultraviolet Light on Subsequent Ripening of the Fruit of the Tomato
      (Lycopersicon esculentum).

PMID- 16654130
TI  - Influence of High, Medium, and Low Soil Moisture on Growth and Alkaloid Content
      of Cinchona ledgeriana.

PMID- 16654131
TI  - Distribution of Thiamin and Riboflavin in the Tomato Plant.

PMID- 16654132
TI  - The Absorption of Phosphorus and Iron from Nutrient Solutions.

PMID- 16654133
TI  - Selectivity of 2,4-D and Sinox When Applied to Soil.

PMID- 16654134
TI  - Soluble Solids Content of Different Regions of Watermelons.

PMID- 16654135
TI  - Notes.

PMID- 16654136
TI  - IN MEMORIAM: FRANCIS ERNEST LLOYD 1868-1947.

PMID- 16654137
TI  - THE EFFECT OF VARYING AMOUNTS OF POTASSIUM ON THE GROWTH AND POTASSIUM
      ACCUMULATION OF YOUNG APPLE TREES.

PMID- 16654138
TI  - STUDIES IN THE METABOLISM OF CRASSULACEAN PLANTS: THE EFFECT OF TEMPERATURE UPON
      THE CULTURE OF EXCISED LEAVES OF BRYOPHYLLUM CALYCINUM.

PMID- 16654139
TI  - VITAMIN C CONTENT OF WALNUTS (PERSIAN) DURING GROWTH AND DEVELOPMENT.

PMID- 16654140
TI  - PECTIC CONTENT OF APPLES IN RELATION TO THIOCYANATE SPRAYS.

PMID- 16654141
TI  - CORRECTION OF DATA FOR PROTEIN NITROGEN IN LEAVES OF BRYOPHYLLUM CALYCINUM.

PMID- 16654142
TI  - RECOVERY OF TURGOR BY CUT SHOOTS AFTER WILTING.

PMID- 16654144
TI  - THE ACTION OF TRI-IODOBENZOIC ACID ON GROWTH.

PMID- 16654143
TI  - DIURNAL FLUCTUATIONS OF GROWTH IN LENGTH OF TOMATO STEM.

PMID- 16654145
TI  - CHLOROSIS AND NODULATION OF COWPEAS AS AFFECTED BY TRIAL SULPHUR APPLICATIONS TO
      CALCAREOUS SOIL IN THE GREENHOUSE.

PMID- 16654146
TI  - NOTES.

PMID- 16654148
TI  - THE EFFECT OF SOME ENVIRONMENTAL FACTORS ON THE MOVEMENTS OF GUARD CELLS.

PMID- 16654147
TI  - DIURNAL CHANGES AND GROWTH RATES AS ASSOCIATED WITH ASCORBIC ACID, TITRATABLE
      ACIDITY, CARBOHYDRATE AND NITROGENOUS FRACTIONS IN THE LEAVES OF ANANAS COMOSUS
      (L.) MERR.

PMID- 16654149
TI  - THE EFFECT OF 2,4-DICHLOROPHENOXYACETIC ACID ON THE RESPIRATORY METABOLISM OF
      BEAN STEM TISSUE.

PMID- 16654150
TI  - A RAPID METHOD FOR THE MEASUREMENT OF THE INHIBITION OF DETERIORATION IN INTACT
      SEEDS.

PMID- 16654151
TI  - THE DETERMINATION OF PECTIC MATERIALS IN APPLES. THE USE OF 19 PER CENT.
      HYDROCHLORIC ACID AND PECTINOL A.

PMID- 16654152
TI  - CARBOHYDRATE ACCUMULATION IN THE COTTON PLANT AT LOW MOISTURE LEVELS.

PMID- 16654153
TI  - ELECTRICAL AND CURVATURE RESPONSES OF THE AVENA COLEOPTILE TO TRANSVERSELY
      APPLIED DIRECT CURRENT.

PMID- 16654154
TI  - RELATION OF WATER TO THE GERMINATION OF CORN AND COTTON SEEDS.

PMID- 16654155
TI  - EFFECT OF NUTRIENT LEVEL ON THE GROWTH AND CHEMICAL COMPOSITION OF SWEETPOTATOES
      IN SAND CULTURES.

PMID- 16654156
TI  - A SURVEY OF THE POSSIBILITIES AND METHODS OF BREEDING HIGH-NIACIN CORN (MAIZE).

PMID- 16654157
TI  - NOTES.

PMID- 16654158
TI  - BURTON EDWARD LIVINGSTON 1875-1948.

PMID- 16654159
TI  - MINERAL ACCUMULATION IN CORN.

PMID- 16654160
TI  - NOTE ON FLOWER FORMATION IN THE PINEAPPLE INDUCED BY LOW NIGHT TEMPERATURES.

PMID- 16654161
TI  - POTASSIUM DEFICIENCY AND EXCESS IN GUAYULE I. GROWTH RESPONSES AND MINERAL
      CONTENT.

PMID- 16654162
TI  - EFFECT OF THE ROOTSTOCK ON THE COMPOSITION OF CITRUS TREES AND FRUIT.

PMID- 16654163
TI  - THE CARBOHYDRATE CONSTITUENTS OF SCENEDESMUS IN RELATION TO THE ASSIMILATION OF
      CARBON BY PHOTOREDUCTION.

PMID- 16654164
TI  - THE INFLUENCE OF CERTAIN ROOTSTOCKS AND SCIONS ON THE ASCORBIC ACID CONTENT OF
      POTATO TUBERS.

PMID- 16654165
TI  - THE EFFECT OF THREE FACTORIAL LEVELS OF NITROGEN AND PHOSPHORUS ON THE GROWTH AND
      COMPOSITION OF CINCHONA LEDGERIANA.

PMID- 16654166
TI  - PHOSPHORUS TURNOVER AND PHOTOSYNTHESIS.

PMID- 16654167
TI  - CHANGES IN CHEMICAL COMPOSITION AND BIOLOGICAL ACTIVITY OF DEVELOPING TUNG FRUIT
      WITH REFERENCE TO OIL SYNTHESIS.

PMID- 16654168
TI  - INFLUENCE OF LIGHT INTENSITY UPON THE CONCENTRATION OF THIAMIN AND RIBOFLAVIN IN
      PLANTS.

PMID- 16654170
TI  - PROTOPLASMIC CHANGES DURING NUCLEAR DIVISION IN POLLEN MOTHER-CELLS AND
      MICROSPORES OF TRILLIUM ERECTUM.

PMID- 16654169
TI  - BLOSSOMING AND PIGMENT CONTENT.

PMID- 16654171
TI  - NOTES.

PMID- 16654172
TI  - POTASSIUM DEFICIENCY AND EXCESS IN GUAYULE. II. CATION-ANION BALANCE IN THE
      LEAVES.

PMID- 16654173
TI  - EFFECTS OF POTASSIUM DEFICIENCY AND EXCESS UPON CERTAIN CARBOHYDRATE AND
      NITROGENOUS CONSTITUENTS IN GUAYULE.

PMID- 16654174
TI  - INVESTIGATIONS ON THE FLUOROMETRIC DETERMINATION OF MALIC AND SUCCINIC ACIDS IN
      APPLE TISSUE.

PMID- 16654175
TI  - THE ABSORPTION AND FLUORESCENCE SPECTRA OF TWO RED MARINE ALGAE.

PMID- 16654176
TI  - PHYSIOLOGICAL STUDIES OF WEED SEED GERMINATION.

PMID- 16654177
TI  - RATE OF LEAF ELONGATION AS AFFECTED BY THE INTENSITY OF THE TOTAL SOIL MOISTURE
      STRESS.

PMID- 16654178
TI  - GASEOUS LOSSES OF NITROGEN FROM GREEN PLANTS. I. STUDIES WITH CHLORELLA AND
      LEMNA.

PMID- 16654179
TI  - THE ROLE OF ACTIVE WATER ABSORPTION IN AUXIN-INDUCED WATER UPTAKE BY AERATED
      POTATO DISCS.

PMID- 16654180
TI  - THE EFFECT OF CALCIUM AND OTHER IONS ON THE EARLY DEVELOPMENT OF THE RADICLE OF
      COTTON SEEDLINGS.

PMID- 16654182
TI  - A COMPARISON OF ELECTRIC RESISTANCE UNITS FOR MAKING A CONTINUOUS MEASUREMENT OF
      SOIL MOISTURE UNDER FIELD CONDITIONS.

PMID- 16654181
TI  - THE IDENTIFICATION OF ETHYLENE AS A VOLATILE PRODUCT OF RIPENING AVOCADOS.

PMID- 16654183
TI  - RESPONSE OF KALANCHOE TUBIFLORA TO X-RADIATION.

PMID- 16654184
TI  - A MICROCHEMICAL EXAMINATION OF McINTOSH APPLE LEAVES SHOWING RELATIONSHIP OF CELL
      WALL CONSTITUENTS TO PENETRATION OF SPRAY SOLUTIONS.

PMID- 16654185
TI  - SOIL TEMPERATURE AS A FACTOR IN THE FRENCHING OF TOBACCO (NICOTIANA TABACUM L.).

PMID- 16654186
TI  - UNAVAILABILITY OF IRON AS A CAUSE OF FRENCHING OF TOBACCO (NICOTIANA TABACUM L.).

PMID- 16654187
TI  - PHOTOSYNTHESIS IN RELATION TO STOMATAL FREQUENCY AND DISTRIBUTION.

PMID- 16654188
TI  - GASEOUS LOSSES OF NITROGEN FROM GREEN PLANTS. II. STUDIES WITH EXCISED LEAVES IN
      NUTRIENT MEDIA.

PMID- 16654189
TI  - THE EFFECT OF THE INTERRELATIONSHIP OF BORON AND MANGANESE ON THE GROWTH AND
      CALCIUM UPTAKE OF BLUE LUPINE (LUPINUS ANGUSTIFOLIUS L.) IN SOLUTION CULTURE.

PMID- 16654190
TI  - CONTRIBUTION OF STUDIES WITH THE ELECTRON MICROSCOPE TO STUDIES OF THE
      RELATIONSHIP OF CHROMOPLASTS TO CAROTENE BODIES AND CAROTENE BODIES TO VITAMIN A.

PMID- 16654191
TI  - A FACTOR METHOD FOR THE AREA OF TOMATO LEAVES.

PMID- 16654192
TI  - A TECHNIQUE FOR INTRODUCING RADIOACTIVE PHOSPHORUS INTO THE GRAIN OF GROWING
      CORN.

PMID- 16654193
TI  - NOTES.

PMID- 16654194
TI  - COPPER ENZYMES IN ISOLATED CHLOROPLASTS. POLYPHENOLOXIDASE IN BETA VULGARIS.

PMID- 16654195
TI  - LOCALIZATION OF PHOSPHORYLASE AND OF STARCH FORMATION IN SEEDS.

PMID- 16654196
TI  - CARBON AND NITROGEN BALANCE OF CHLORELLA DURING GROWTH.

PMID- 16654197
TI  - THE CHEMICAL COMPOSITION OF CHLORELLA; EFFECT OF ENVIRONMENTAL CONDITIONS.

PMID- 16654198
TI  - THE EFFECT ON THE GROWTH OF PEANUTS OF NUTRIENT DEFICIENCIES IN THE ROOT AND THE
      PEGGING ZONE.

PMID- 16654199
TI  - INFLUENCE OF FERTILIZER TREATMENT ON THE CHEMICAL COMPOSITION OF MOORE PECAN
      LEAVES DURING NUT DEVELOPMENT.

PMID- 16654200
TI  - TETRAZOLIUM CHLORIDE AS A TEST REAGENT FOR FREEZING INJURY OF SEED CORN.

PMID- 16654201
TI  - SOME ASPECTS OF THE STATE OF CHLOROPHYLL IN CHLOROPLASTS.

PMID- 16654202
TI  - THE ACTION OF GROWTH INHIBITORS ON CARBOHYDRATE METABOLISM IN THE PEA.

PMID- 16654203
TI  - SEVENTIETH ANNIVERSARY OF CHARLES ALBERT SHULL: JANUARY 19, 1949.

PMID- 16654204
TI  - EFFECTS OF PHOTOPERIOD AND TEMPERATURE ON GROWTH AND FLOWERING OF KENTUCKY
      BLUEGRASS.

PMID- 16654206
TI  - RELATION BETWEEN ROOT RESPIRATION AND ABSORPTION.

PMID- 16654205
TI  - THE USE OF GROWTH-REGULATING CHEMICALS TO INDUCE PARTHENOCARPIC FRUIT IN THE
      CALIMYRNA FIG.

PMID- 16654207
TI  - EFFECTS OF 2,4-D ON INBRED LINES AND A SINGLE CROSS OF MAIZE.

PMID- 16654208
TI  - BUFFER INDEX VALUES IN RELATION TO SOIL-pH TOLERANCES.

PMID- 16654209
TI  - OBSERVATIONS ON THE MECHANISM OF AUXIN FORMATION IN PLANT TISSUES.

PMID- 16654210
TI  - SOME FACTORS AFFECTING GERMINATION OF CELERY SEED.

PMID- 16654211
TI  - SOME RESPONSES OF PLANTS TO 2,3,5-TRIIODOBENZOIC ACID.

PMID- 16654212
TI  - THE NATURE OF THE AUXIN IN TOMATO STEM TIPS.

PMID- 16654213
TI  - TIME COURSE OF PHOTOSYNTHESIS IN APPLE LEAVES EXPOSED TO CONTINUOUS ILLUMINATION.

PMID- 16654214
TI  - INHIBITORS OF HEATING AND DETERIORATION IN SEEDS. I. ETHYLENE CHLORHYDRIN AND
      RELATED COMPOUNDS.

PMID- 16654215
TI  - EFFECTS OF STARVATION ON THE METABOLISM OF CHLORELLA.

PMID- 16654217
TI  - EFFECT OF PHYTOHORMONES ON POTATO GROWTH AND THE SIZE OF THE STARCH GRANULES.

PMID- 16654216
TI  - THE RELATIONSHIP OF RIBOFLAVIN AND ASCORBIC ACID TO CARBOHYDRATE AND NITROGEN
      FRACTIONS IN IMMATURE OAT PLANTS AS INFLUENCED BY MINERAL DEFICIENCIES.

PMID- 16654218
TI  - THE APPLICATION OF THE TOTAL AVAILABLE CARBOHYDRATE METHOD TO THE STUDY OF
      CARBOHYDRATE RESERVES OF SWITCH CANE (ARUNDINARA TECTA).

PMID- 16654220
TI  - THE FUNCTION OF MANGANESE IN THE ASSIMILATION OF NITRATES.

PMID- 16654219
TI  - CHANGES IN CHEMICAL COMPOSITION OF THE STEMS OF RED KIDNEY BEAN PLANTS TREATED
      WITH 2, 4-DICHLOROPHENOXYACETIC ACID.

PMID- 16654221
TI  - THE OXIDASE OF THE APRICOT.

PMID- 16654223
TI  - A SIMPLE AERATOR FOR NUTRIENT SOLUTIONS.

PMID- 16654222
TI  - "THERMAL MACERATION" OF PLANT TISSUE.

PMID- 16654224
TI  - DETERMINATION OF CAROTENE IN SWEET POTATOES.

PMID- 16654226
TI  - NOTES.

PMID- 16654225
TI  - CONIFEROUS ROOT EXUDATE.

PMID- 16654227
TI  - THE PROBLEM OF SELECTING UNIFORM SAMPLES OF LEAVES.

PMID- 16654228
TI  - GROWTH AND COMPOSITION OF BILOXI SOYBEAN GROWN IN A CONTROLLED ENVIRONMENT WITH
      RADIATION FROM DIFFERENT CARBON-ARC SOURCES.

PMID- 16654229
TI  - GROWTH REGULATION BY ORGANIC COMPOUNDS.

PMID- 16654230
TI  - THE NITROGEN COMPOSITION OF CEREAL GRASSES. I. PRINCIPAL NITROGEN FRACTIONS.

PMID- 16654231
TI  - ORGANIC ACIDS OF THE COTTON PLANT.

PMID- 16654232
TI  - THE TOPOGRAPHICAL TETRAZOLIUM METHOD FOR DETERMINING THE GERMINATING CAPACITY OF
      SEEDS.

PMID- 16654233
TI  - POTASSIUM IN CITRUS TREES.

PMID- 16654234
TI  - GROWTH AND CHEMICAL COMPOSITION OF ANANAS COMOSUS (L.) MERR., IN SOLUTION
      CULTURES WITH DIFFERENT IRON-MANGANESE RATIOS.

PMID- 16654235
TI  - AUTONOMIC DIURNAL CYCLES IN THE WATER RELATIONS OF NONEXUDING DETOPPED ROOT
      SYSTEMS.

PMID- 16654236
TI  - THE INFLUENCE OF ROOTSTOCK ON THE MINERAL COMPOSITION OF VALENCIA ORANGE LEAVES.

PMID- 16654237
TI  - THE EFFECTS OF SOME INHIBITORS OF PHOTOSYNTHESIS UPON THE PHOTOCHEMICAL REDUCTION
      OF A DYE BY ISOLATED CHLOROPLASTS.

PMID- 16654238
TI  - ORANGE FRUITING IN RELATION TO THE BLOSSOM OPENING PERIOD.

PMID- 16654239
TI  - A STUDY OF CHEMOTROPISM OF POLLEN TUBES IN VITRO.

PMID- 16654241
TI  - MOVEMENT OF P IN MATURING CORN PLANTS.

PMID- 16654240
TI  - THE EFFECT OF TEMPERATURE UPON TRANSLOCATION OF CARBOHYDRATES IN THE TOMATO
      PLANT.

PMID- 16654242
TI  - FLOWER INITIATION IN TOTAL DARKNESS.

PMID- 16654243
TI  - THE EFFECT OF TEMPERATURE ON THE SUSCEPTIBILITY OF PLANTS TO 2,4-D.

PMID- 16654244
TI  - A METHOD FOR THE STUDY OF FOLIAR ABSCISSION IN VITRO.

PMID- 16654245
TI  - RELATION OF WATER TO THE GERMINATION OF BEAN SEEDS.

PMID- 16654247
TI  - NOTES.

PMID- 16654246
TI  - EFFECT OF 2,4-DICHLOROPHENOXYACETIC ACID ON THE CONTENT OF THIAMINE, RIBOFLAVIN,
      NICOTINIC ACID, PANTOTHENIC ACID AND CAROTENE IN STEMS AND LEAVES OF RED KIDNEY
      BEAN PLANTS.

PMID- 16654248
TI  - EFFECT OF CERTAIN GROWTH REGULATORS ON SEED STALK DEVELOPMENT IN LETTUCE AND
      CELERY.

PMID- 16654249
TI  - INDOLEACETIC-NICOTINIC ACID INTERACTIONS IN THE ETIOLATED PEA PLANT.

PMID- 16654250
TI  - THE EFFECT OF ONION JUICE ON THE GROWTH RESPONSE TO AUXIN.

PMID- 16654251
TI  - RESPONSES OF PLANT CELLS TO HERBICIDES.

PMID- 16654252
TI  - STUDIES IN THE METABOLISM OF CRASSULACEAN PLANTS: DIURNAL VARIATION OF ORGANIC
      ACIDS AND STARCH IN EXCISED LEAVES OF BRYOPHYLLUM CALYCINUM.

PMID- 16654253
TI  - EFFECTS OF GROWTH SUBSTANCES ON PHOTOSYNTHESIS.

PMID- 16654254
TI  - FREEZING INJURY OF MAIZE SEED.

PMID- 16654255
TI  - PHOTOPERIODIC CHLOROSIS IN TOMATO.

PMID- 16654256
TI  - INFLUENCE OF POTASSIUM AND BORON ON NUTRIENT-ELEMENT BALANCE IN AND GROWTH OF
      RANGER ALFALFA.

PMID- 16654257
TI  - CARBOHYDRATE FRACTIONS OF LEMON PEEL.

PMID- 16654258
TI  - THE EFFECT OF TEMPERATURE ON THE GROWTH AND COMPOSITION OF THE STUBBLE AND ROOTS
      OF PERENNIAL RYEGRASS.

PMID- 16654259
TI  - EXPERIMENTS ON SUCROSE FORMATION BY POTATO TUBERS AS INFLUENCED BY TEMPERATURE.

PMID- 16654260
TI  - EFFECTS OF VARIATIONS IN THE ROOT-LEAF RATIO ON TRANSPIRATION RATE.

PMID- 16654261
TI  - BIOCHEMICAL CHANGES IN TERMINAL TUNG BUDS DURING THEIR EXPANSION PRIOR TO
      BLOSSOMING.

PMID- 16654262
TI  - EFFECTS OF PHOTOPERIOD AND NITROGEN SUPPLY ON GROWTH AND REPRODUCTION IN THE
      GHERKIN.

PMID- 16654263
TI  - EFFECT OF 2,4-D ON YIELDS OF MAIZE IN THE SUCCEEDING GENERATION AFTER TREATMENT.

PMID- 16654265
TI  - OTIS FREEMAN CURTIS: 1888-1949.

PMID- 16654264
TI  - NOTES.

PMID- 16654266
TI  - THE INFLUENCE OF CALCIUM ION ACTIVITY IN WATER CULTURES ON THE INTAKE OF CATIONS
      BY BEAN PLANTS.

PMID- 16654267
TI  - GREENHOUSE TESTS WITH CHEMICALS FOR SUPPRESSION OF LATERAL BRANCHING OF
      DECAPITATED TOBACCO PLANTS.

PMID- 16654268
TI  - HISTOLOGICAL STRUCTURE OF POTATO STEMS AND LEAVES AS INFLUENCED BY MANGANESE
      TOXICITY.

PMID- 16654269
TI  - THE MOLECULAR WEIGHT OF RUBBER IN DIFFERENT PARTS OF THE GUAYULE PLANT.

PMID- 16654270
TI  - A STUDY OF THE PHYSIOLOGICAL EFFECTS OF ELEMENTAL SULPHUR DUST ON CITRUS FRUITS.

PMID- 16654271
TI  - ON THE THEORETICAL INTERPRETATION OF TURGOR PRESSURE.

PMID- 16654272
TI  - TRANSLOCATION OF EXOGENOUS GROWTH-REGULATORS IN THE BEAN SEEDLING.

PMID- 16654273
TI  - INFLUENCE OF TEMPERATURE ON THE VITAMIN CONTENT OF GREEN PLANTS.

PMID- 16654274
TI  - FURTHER STUDIES ON THE CHEMICAL INDUCTION OF PARTHENOCARPY IN THE CALIMYRNA FIG.

PMID- 16654275
TI  - CHANGES IN THE CARBOHYDRATE METABOLISM OF TARAXACUM KOK-SAGHYZ ROD DURING THE
      FIRST AND SECOND YEARS OF GROWTH.

PMID- 16654276
TI  - ARSENATE AS A SELECTIVE INHIBITOR OF GROWTH SUBSTANCE ACTION.

PMID- 16654277
TI  - SIMPLIFIED EQUIPMENT FOR SUBIRRIGATION EXPERIMENTS IN PLANT NUTRITION.

PMID- 16654278
TI  - NOTES.

PMID- 16654279
TI  - THE INFLUENCE OF MINERAL DEFICIENCY ON VEGETATIVE GROWTH, FLOWER AND FRUIT
      PRODUCTION, AND MINERAL COMPOSITION OF THE PEANUT PLANT.

PMID- 16654280
TI  - CORRELATION BETWEEN LEAF COLOR, LEAF NITROGEN CONTENT, AND GROWTH OF APPLE,
      PEACH, AND GRAPE PLANTS.

PMID- 16654281
TI  - A MODIFIED CIRCUIT FOR SLIMLINE FLUORESCENT LAMPS FOR PLANT GROWTH CHAMBERS.

PMID- 16654282
TI  - RESERVE CARBOHYDRATES IN ORCHARD GRASS CLIPPED PERIODICALLY.

PMID- 16654283
TI  - DENNIS ROBERT HOAGLAND: 1884-1949.

PMID- 16654284
TI  - GROWTH AND NUTRIENT ACCUMULATION AS CONTROLLED BY OXYGEN SUPPLY TO PLANT ROOTS.

PMID- 16654285
TI  - COMPOSITION OF DEVELOPING PEANUT SEED.

PMID- 16654287
TI  - HYGROSCOPIC EQUILIBRIUM AND VIABILITY OF NATURALLY AND ARTIFICIALLY DRIED BLUE
      LUPINE SEEDS.

PMID- 16654286
TI  - BASES FOR THE PREDICTION OF CORN YIELDS.

PMID- 16654288
TI  - THE RELATION OF THE CHARACTERISTICS AND YIELD OF WAX TO PLANT AGE.

PMID- 16654289
TI  - ACCUMULATION OF FREE AMINO ACIDS AS A CHEMICAL BASIS FOR MORPHOLOGICAL SYMPTOMS
      IN TOBACCO MANIFESTING FRENCHING AND MINERAL DEFICIENCY SYMPTOMS.

PMID- 16654290
TI  - CHANGES IN CHEMICAL COMPOSITION OF THE LEAVES AND ROOTS OF RED KIDNEY BEAN PLANTS
      TREATED WITH 2, 4-DICHLOROPHENOXYACETIC ACID.

PMID- 16654291
TI  - CHLOROPHYLL STUDIES ON BARLEY MUTANTS.

PMID- 16654292
TI  - MANGANESE INTERFERENCE IN THE ABSORPTION AND TRANSLOCATION OF RADIOACTIVE IRON
      (Fe) IN ANANAS COMOSUS (L.) MERR.

PMID- 16654293
TI  - THE GROWTH AND METABOLISM OF EXCISED ROOTS IN CULTURE. I. THE MEASUREMENT OF
      GROWTH AND THE ROLE OF CERTAIN VITAMINS.

PMID- 16654294
TI  - THE GROWTH AND METABOLISM OF EXCISED ROOTS IN CULTURE. II. THE RESPIRATORY RATES
      OF EXCISED TOMATO ROOTS.

PMID- 16654296
TI  - A MODIFICATION OF THE WARBURG RESPIROMETER TO MEASURE THE RESPIRATION RATE OF
      TOMATO LEAF DISCS.

PMID- 16654295
TI  - A SOFT X-RAY MUTANT OF ASPERGILLUS NIGER VAN TIEGHEM.

PMID- 16654297
TI  - PRECAUTIONS IN THE USE OF LANOLIN AS AN ASSAY DILUENT FOR PLANT GROWTH
      SUBSTANCES.

PMID- 16654298
TI  - NOTES.

PMID- 16654299
TI  - FURTHER OBSERVATIONS ON THE ABSORPTION AND TRANSLOCATION OF INORGANIC SOLUTES
      USING RADIOACTIVE ISOTOPES WITH PLANTS.

PMID- 16654300
TI  - THE EFFECT OF SOIL TEMPERATURE ON GUAYULE PLANTS.

PMID- 16654301
TI  - THE ORTHO EFFECT IN PLANT GROWTH-REGULATORS.

PMID- 16654302
TI  - THE EFFECT OF NITROGEN AND POTASSIUM LEVELS IN TUNG SEEDLINGS ON GROWTH, APPARENT
      PHOTOSYNTHESIS, AND CARBOHYDRATE COMPOSITION.

PMID- 16654303
TI  - MOISTURE ABSORPTION BY PLANTS FROM AN ATMOSPHERE OF HIGH HUMIDITY.

PMID- 16654304
TI  - SOME GROSS CORRELATIONS BETWEEN GROWTH ENLARGEMENT AND THE SOLUTE AND WATER
      RELATIONS OF PLANTS, WITH SPECIAL EMPHASIS ON THE RELATION OF TURGOR PRESSURE TO
      DISTENTION OF CELLS.

PMID- 16654305
TI  - IS THE AMERICAN ELM (ULMUS AMERICANA) INJURED BY NATURAL GAS?

PMID- 16654306
TI  - THE EFFECT OF IRRIGATION, NITROGEN LEVEL AND SEASON ON THE COMPOSITION OF
      CABBAGE.

PMID- 16654307
TI  - THE EFFECTS OF FLOODING ON THE TRANSPIRATION AND SURVIVAL OF SOME SOUTHEASTERN
      FOREST TREE SPECIES.

PMID- 16654308
TI  - SOME OBSERVATIONS ON NITRITE FORMATION AND THE ABSORPTION OF NITROGEN BY CITRUS.

PMID- 16654309
TI  - EFFECTS OF SOME GROWTH REGULATING SUBSTANCES ON THE TRANSPIRATION OF ZEA MAYS, L.
      AND RICINUS COMMUNIS, L.

PMID- 16654310
TI  - RESPIRATION STUDIES ON CHLORELLA. I. GROWTH EXPERIMENTS WITH ACID INTERMEDIATES.

PMID- 16654311
TI  - MINERAL COMPOSITION OF CHLOROTIC ORANGE LEAVES AND SOME OBSERVATIONS ON THE
      RELATION OF SAMPLE PREPARATION TECHNIQUE TO THE INTERPRETATION OF RESULTS.

PMID- 16654313
TI  - THE CENTRIFUGE METHOD FOR MEASURING NECTAR YIELD.

PMID- 16654312
TI  - GENERAL USES AND METHODS OF THERMISTORS IN TEMPERATURE INVESTIGATIONS, WITH
      SPECIAL REFERENCE TO A TECHNIQUE FOR HIGH SENSITIVITY CONTACT TEMPERATURE
      MEASUREMENT.

PMID- 16654314
TI  - CYTOCHROME OXIDASE IN CORN EMBRYOS.

PMID- 16654315
TI  - EFFECT OF 2,4-DICHLOROPHENOXYACETIC ACID ON THE INVERTASE, PHOSPHORYLASE AND
      PECTIN METHOXYLASE ACTIVITY IN THE STEMS AND LEAVES OF THE RED KIDNEY BEAN
      PLANTS.

PMID- 16654316
TI  - THE STATUS OF PLANT PHYSIOLOGY IN THE UNITED STATES: THE NUMBER, INTERESTS AND
      RATE OF TRAINING OF PLANT PHYSIOLOGISTS.

PMID- 16654317
TI  - THE EFFECT OF PREHARVEST FOLIAGE SPRAYS OF CERTAIN GROWTH REGULATORS ON SPROUT
      INHIBITION AND STORAGE QUALITY OF CARROTS AND ONIONS.

PMID- 16654318
TI  - INTERACTION OF CYSTINE AND CASEIN HYDROLYSATE DURING THE AUTOCLAVING OF A
      MICROBIOLOGICAL ASSAY MEDIUM.

PMID- 16654319
TI  - MOLYBDENUM NUTRITION OF ALFALFA.

PMID- 16654320
TI  - GROWTH OF WALNUT TREES AS AFFECTED BY IRRIGATION AND NITROGEN DEFICIENCY.

PMID- 16654321
TI  - CHELATION OF TRACE METALS IN NUTRIENT SOLUTIONS.

PMID- 16654322
TI  - INHIBITION OF CURVATURE RESPONSES BY SHUNTING THE INHERENT ELECTRICAL FIELD.

PMID- 16654323
TI  - GROWTH OF ANANAS COMOSUS (L.) MERR. AT DIFFERENT LEVELS OF MINERAL NUTRITION
      UNDER GREENHOUSE AND FIELD CONDITIONS. I. PLANT AND FRUIT WEIGHTS AND ABSORPTION
      OF NITRATE AND POTASSIUM AT DIFFERENT GROWTH INTERVALS.

PMID- 16654324
TI  - A STUDY OF CERTAIN NUTRIENT LEVELS FOR RASPBERRIES GROWN IN WATER CULTURES.

PMID- 16654325
TI  - CATALASE ACTIVITY IN CHLOROPLAST PIGMENT DEFICIENT TYPES OF CORN.

PMID- 16654326
TI  - A STUDY OF POTASSIUM ABSORPTION BY BARLEY ROOTS.

PMID- 16654327
TI  - THE ACTION OF INHIBITORS ON WATER UPTAKE BY POTATO TISSUE.

PMID- 16654328
TI  - THE PHOSPHORUS UPTAKE OF ANDROPOGON ISCHAEMUM L. AT VARIOUS STAGES OF
      DEVELOPMENT.

PMID- 16654329
TI  - SULPHUR DIOXIDE FUMIGATION OF WHEAT WITH SPECIAL REFERENCE TO ITS EFFECT ON
      YIELD.

PMID- 16654330
TI  - GROWTH RESPONSES OF TOMATO TO NUTRIENT IONS ADSORBED ON A PUMICE SUBSTRATE.

PMID- 16654332
TI  - IN VITRO TESTS OF ABSCISSION AGENTS.

PMID- 16654331
TI  - SEASONAL FLUCTUATIONS OF ROOT RESERVES IN RED CLOVER, TRIFOLIUM PRATENSE L.

PMID- 16654333
TI  - INHIBITION OF NITRATE ASSIMILATION IN EXCISED WHEAT ROOTS BY VARIOUS RESPIRATORY
      POISONS.

PMID- 16654334
TI  - FLUORINE TOXICITY IN TOMATO AS MODIFIED BY ALTERATIONS IN THE NITROGEN, CALCIUM,
      AND PHOSPHORUS NUTRITION OF THE PLANT.

PMID- 16654336
TI  - THE PHOTOINACTIVATION OF ENZYMES BY RIBOFLAVIN.

PMID- 16654335
TI  - SOIL AERATION AS A FACTOR IN WATER ABSORPTION BY THE ROOTS OF TRANSPIRING PLANTS.

PMID- 16654337
TI  - TECHNIQUE FOR GROWING PLANTS WITH ROOTS IN A STERILE MEDIUM.

PMID- 16654338
TI  - NOTES.

PMID- 16654339
TI  - THE INFLUENCE OF LIGHT, TEMPERATURE, AND SOME ENZYME POISONS UPON THE TOTAL
      ORGANIC ACID CONTENT OF LEAF TISSUE OF KALANCHOE DAIGREMONTIANA (HAMET AND
      PERRIER).

PMID- 16654340
TI  - THE RESPONSE OF YOUNG VALENCIA ORANGE TREES TO DIFFERENTIAL BORON SUPPLY IN SAND
      CULTURE.

PMID- 16654341
TI  - EFFECTS OF DIFFERENT CONCENTRATIONS OF NITRATE ON THE GROWTH AND VITAMIN CONTENT
      OF OAT PLANTS.

PMID- 16654342
TI  - THE AMINO ACIDS OF ALFALFA AS REVEALED BY PAPER CHROMATOGRAPHY WITH SPECIAL
      REFERENCE TO COMPOUNDS LABELLED WITH S.

PMID- 16654343
TI  - HORMONE-INDUCED PARTHENOCARPY IN THE CALIMYRNA FIG AND A COMPARISON OF
      PARTHENOCARPIC AND CAPRIFIED SYCONIA.

PMID- 16654344
TI  - EFFECTS OF SOIL TEMPERATURE AND LIGHT INTENSITY ON ROOT GROWTH OF LOBLOLLY PINE
      SEEDLINGS.

PMID- 16654345
TI  - DYE REDUCTION BY ILLUMINATED CHLOROPLAST FRAGMENTS.

PMID- 16654346
TI  - THE BIOSYNTHESIS OF CARBON-14-LABELED COMPOUNDS. I. THE CHROMATOGRAPHIC
      SEPARATION OF GLUCOSE AND FRUCTOSE.

PMID- 16654347
TI  - THE SUGARS OF THE HEMICELLULOSES OF CORNSTALKS.

PMID- 16654348
TI  - SUCCINIC ACID CONTENT OF THE COTTON PLANT.

PMID- 16654349
TI  - AUXIN IN RELATION TO LEAF BLADE ABSCISSION.

PMID- 16654350
TI  - THE BIOELECTRIC POTENTIAL OF SEEDS AS A FUNCTION OF GROWTH AND OF X-RAY DOSAGE.

PMID- 16654351
TI  - COLORIMETRIC ESTIMATION OF INDOLEACETIC ACID.

PMID- 16654352
TI  - CONSTANT-TEMPERATURE BATHS FOR USE IN FREEZING-POINT MEASUREMENTS.

PMID- 16654353
TI  - NOTES.

PMID- 16654354
TI  - EFFECTS OF RESPIRATION INHIBITORS ON ACCUMULATION OF RADIOACTIVE PHOSPHORUS BY
      ROOTS OF LOBLOLLY PINE.

PMID- 16654355
TI  - INFLUENCE OF ACIDITY, CALCIUM AND MAGNESIUM ON GROWTH OF XANTHI TOBACCO IN WATER
      CULTURE.

PMID- 16654356
TI  - PHOTOSYNTHESIS IN NATURALLY REARED AQUATIC COMMUNITIES.

PMID- 16654357
TI  - EFFECTS OF NON-LETHAL CONCENTRATIONS OF 2,4-D ON BUCKWHEAT.

PMID- 16654358
TI  - THE ISOLATION AND PRELIMINARY FRACTIONATION OF PROTEINS FROM DORMANT AND GROWING
      POTATO TUBERS.

PMID- 16654359
TI  - PHYSIOLOGICAL STUDIES OF THE FRUITS OF THE PINEAPPLE [ANANAS COMOSUS (L.) MERR.]
      WITH SPECIAL REFERENCE TO PHYSIOLOGICAL BREAKDOWN.

PMID- 16654360
TI  - THE NUTRITIONAL STATUS OF THE COTTON PLANT AS INDICATED BY TISSUE TESTS.

PMID- 16654361
TI  - ASCORBIC ACID AND DRY MATTER ACCUMULATION IN TURNIP AND BROCCOLI LEAF DISCS AFTER
      INFILTRATION WITH INORGANIC SALTS, ORGANIC ACIDS, AND SOME ENZYME INHIBITORS.

PMID- 16654362
TI  - STOMATAL MOVEMENT AND PHOTOSYNTHESIS IN PELARGONIUM. I. EFFECTS OF LIGHT AND
      CARBON DIOXIDE.

PMID- 16654363
TI  - PHOTOSYNTHESIS AND METABOLISM OF ORGANIC ACIDS IN HIGHER PLANTS.

PMID- 16654364
TI  - THE EFFECTS OF SOME SPECIAL TREATMENTS IN THE DEGREENING OF FLORIDA ORANGES AS
      MEASURED BY RESPIRATION RATE.

PMID- 16654365
TI  - COMPARISONS OF GROWTH BY TOBACCO AND SUNFLOWER TISSUE ON SYNTHETIC MEDIA
      CONTAINING VARIOUS SOURCES OF ORGANIC NITROGEN.

PMID- 16654366
TI  - RESPIRATION STUDIES ON CHLORELLA. II. INFLUENCE OF VARIOUS ORGANIC ACIDS ON GAS
      EXCHANGE.

PMID- 16654367
TI  - EFFECT OF VARIOUS FACTORS ON THE UTILIZATION OF NITROGEN AND IRON BY SPIRODELA
      POLYRHIZA (L.) SCHLEID.

PMID- 16654368
TI  - IDENTIFICATION OF ETHYLENE AS A VOLATILE PRODUCT OF THE FUNGUS PENICILLIUM
      DIGITATUM.

PMID- 16654369
TI  - STUDIES ON THE PHYSIOLOGY OF LIGHT ACTION. IV. LIGHT ENHANCEMENT OF AUXIN-INDUCED
      GROWTH IN GREEN PEAS.

PMID- 16654370
TI  - PHOTOTUBE-TYPE INTEGRATING LIGHT RECORDERS: A SUMMARY OF PERFORMANCE OVER A FIVE
      YEAR PERIOD.

PMID- 16654371
TI  - BOUND WATER IN ASPERGILLUS NIGER.

PMID- 16654372
TI  - THE STEROLS OF ALFALFA AND CERTAIN CEREAL GRASSES.

PMID- 16654373
TI  - SOME EFFECTS OF DECAPITATION ON ELECTRICAL AND ELONGATION PHENOMENA IN THE AVENA
      COLEOPTILE.

PMID- 16654374
TI  - AVAILABILITY OF SOIL MOISTURE FOR ACTIVE ABSORPTION IN DRYING SOIL.

PMID- 16654375
TI  - EFFECTS OF FLOODED SOIL ON GROWTH OF PINE SEEDLINGS.

PMID- 16654376
TI  - THE RELATIONSHIP OF STRUCTURE AND PLANT-GROWTH ACTIVITY OF SUBSTITUTED BENZOIC
      AND PHENOXYACETIC ACIDS.

PMID- 16654377
TI  - INVESTIGATIONS ON NITROGEN COMPOUNDS AND NITROGEN METABOLISM IN PLANTS. I. THE
      REACTION OF NITROGEN COMPOUNDS WITH NINHYDRIN ON PAPER: A QUANTITATIVE PROCEDURE.

PMID- 16654378
TI  - A BIOCHEMICAL BASIS FOR COPPER-NITROGEN BALANCE IN TUNG.

PMID- 16654379
TI  - THE FATE OF PHOSPHATASE, INVERTASE, AND PEROXIDASE IN AUTOLYZING LEAVES.

PMID- 16654380
TI  - MAINTENANCE OF IRON SUPPLY IN NUTRIENT SOLUTIONS BY A SINGLE ADDITION OF FERRIC
      POTASSIUM ETHYLENEDIAMINE TETRA-ACETATE.

PMID- 16654382
TI  - NOTES.

PMID- 16654381
TI  - DISTRIBUTION OF MICRONUTRIENT METALS IN LEAVES AND CHLOROPLAST FRAGMENTS.

PMID- 16654383
TI  - INVESTIGATIONS ON NITROGEN COMPOUNDS AND NITROGEN METABOLISM IN PLANTS. II.
      VARIABLES IN TWO-DIRECTIONAL PAPER CHROMATOGRAPHY OF NITROGEN COMPOUNDS: A
      QUANTITATIVE PROCEDURE.

PMID- 16654384
TI  - PHYSIOLOGICAL AND BIOCHEMICAL CHANGES ACCOMPANYING POLLINATION IN ORCHID FLOWERS:
      I. GENERAL OBSERVATIONS AND WATER RELATIONS.

PMID- 16654385
TI  - GROWTH OF ANANAS COMOSUS (L.) MERR., AT DIFFERENT LEVELS OF MINERAL NUTRITION
      UNDER GREENHOUSE AND FIELD CONDITIONS. II. CHEMICAL COMPOSITION OF THE TISSUES AT
      DIFFERENT GROWTH INTERVALS.

PMID- 16654386
TI  - EXPERIMENTS ON THE INHERITANCE OF NIACIN IN CORN (MAIZE).

PMID- 16654387
TI  - TRYPTOPHAN, NIACIN, AND INDOLEACETIC ACID IN SEVERAL ENDOSPERM MUTANTS AND
      STANDARD LINES OF MAIZE.

PMID- 16654388
TI  - MORPHOLOGICAL AND PHYSIOLOGICAL RESPONSES OF CARNATION AND TOMATO TO ORGANIC
      PHOSPHORUS INSECTICIDES AND INORGANIC SOIL PHOSPHORUS.

PMID- 16654389
TI  - TRANSLOCATION OF FOOD RESERVES FROM SOYBEAN COTYLEDONS AND THEIR INFLUENCE ON THE
      DEVELOPMENT OF THE PLANT.

PMID- 16654390
TI  - ON THE MASS CULTURE OF ALGAE.

PMID- 16654391
TI  - THE POSITION OF C IN SUNFLOWER LEAF METABOLITES AFTER EXPOSURE OF LEAVES TO SHORT
      PERIOD PHOTOSYNTHESIS AND DARKNESS IN AN ATMOSPHERE OF CO(2).

PMID- 16654392
TI  - THE EFFECT OF PETIOLE TEMPERATURE ON THE TRANSLOCATION OF CARBOHYDRATES FROM BEAN
      LEAVES.

PMID- 16654393
TI  - TEMPERATURE-INDUCED SAP FLOW IN EXCISED STEMS OF ACER.

PMID- 16654394
TI  - STOMATAL MOVEMENT AND PHOTOSYNTHESIS IN PELARGONIUM. II. EFFECTS OF WATER DEFICIT
      AND OF CHLOROFORM: PHOTOSYNTHESIS IN GUARD CELLS.

PMID- 16654395
TI  - AN OUTLINE OF ENERGETICS IN RELATION TO THE MOVEMENT OF MATERIALS THROUGH A TWO
      PHASED SOLUTION SYSTEM.

PMID- 16654396
TI  - PHYTOTOXICITY OF IMIDAZOLINE DERIVATIVES AND RELATED COMPOUNDS.

PMID- 16654397
TI  - A VIRUS TECHNIQUE USEFUL TO DIAGNOSE FOLIAR DEFICIENCIES.

PMID- 16654398
TI  - SOME EFFECTS OF WATER AND OXYGEN ON ABSCISSION IN VITRO.

PMID- 16654399
TI  - EXPANSION OF CHENOPODIUM ALBUM LEAF DISKS AS AFFECTED BY COUMARIN.

PMID- 16654400
TI  - NOTES.

PMID- 16654401
TI  - SULPHUR NUTRITION OF COTTON.

PMID- 16654402
TI  - FURTHER THEORETICAL CONSIDERATIONS OF MODES OF EXPRESSION AND FACTORS POSSIBLY
      CONCERNED IN THE MOVEMENT OF MATERIALS THROUGH A TWO-PHASED SOLUTION SYSTEM.

PMID- 16654403
TI  - BIOCHEMICAL COMPOSITION OF COTTON LEAVES AND THEIR CHEMICAL DEFOLIATION AS
      AFFECTED BY ENVIRONMENT.

PMID- 16654405
TI  - ENZYMATIC CONVERSION OF INDOLE ACETALDEHYDE AND NAPHTHALENE ACETALDEHYDE TO
      AUXINS.

PMID- 16654404
TI  - DIFFERENCE IN ACTIVITY BETWEEN 2,4-DICHLORO-PHENOXYACETIC ACID AND OTHER AUXINS,
      AND ITS SIGNIFICANCE IN HERBICIDAL ACTION.

PMID- 16654406
TI  - PHYSIOLOGICAL AND BIOCHEMICAL CHANGES ACCOMPANYING POLLINATION IN ORCHID FLOWERS.
      II. RESPIRATION, CATALASE ACTIVITY, AND CHEMICAL CONSTITUENTS.

PMID- 16654407
TI  - CAUSES OF INJURY TO PLANTS RESULTING FROM FLOODING OF THE SOIL.

PMID- 16654408
TI  - THE NUTRIENT-ELEMENT BALANCE OF THE TOMATO AND ITS SUSCEPTIBILITY TO PHYTOPHTHORA
      INFESTANS AS AFFECTED BY TWO LEVELS OF ZINC.

PMID- 16654409
TI  - THE EFFECTS OF THE FORM OF NITROGEN AND THE AMOUNT OF BASE SUPPLY ON THE ORGANIC
      ACIDS OF TUNG LEAVES.

PMID- 16654410
TI  - INVESTIGATIONS OF ASCORBIC ACID DEHYDROGENASE OF PEAS (PISUM SATIVUM) AND ITS
      DISTRIBUTION IN THE DEVELOPING PLANT.

PMID- 16654411
TI  - THE RELATIVE HERBICIDAL EFFECTIVENESS OF SEVERAL DERIVATIVES OF 2,4
      DICHLOROPHENOXYACETIC ACID AND 2,4,5-TRICHLOROPHENOXYACETIC ACID.

PMID- 16654412
TI  - THE GROWTH CAPACITY OF THE SUNFLOWER HYPOCOTYL.

PMID- 16654413
TI  - SOME EFFECTS OF PHOSPHORUS ON THE DEVELOPMENT, THE B VITAMIN CONTENT, AND THE
      INORGANIC COMPOSITION OF OATS.

PMID- 16654414
TI  - AUTORADIOGRAPHY AS AN AID IN DETERMINING THE GROSS ABSORPTION AND UTILIZATION OF
      FOLIAR APPLIED NUTRIENTS.

PMID- 16654415
TI  - NITROGEN AND AMINO ACID CONTENT OF THE VARIOUS PARTS OF ANDROPOGON ISCHAEMUM L.

PMID- 16654416
TI  - OCCURRENCE OF BACILLUS CEREUS IN MARYLAND SOILS WITH FRENCHED TOBACCO.

PMID- 16654417
TI  - FURTHER EVIDENCE FOR A CHEMICAL REACTION BETWEEN PLANT GROWTH-REGULATORS AND A
      PLANT SUBSTRATE.

PMID- 16654418
TI  - THE INFLUENCE OF VARIOUS SODIUM AND POTASSIUM SALTS UPON THE GROWTH OF YOUNG
      AVENA SEEDLINGS.

PMID- 16654419
TI  - ASCORBIC ACID AND ASCORBIC ACID OXIDIZING ENZYMES OF GREEN BEAN PLANTS DEFICIENT
      IN MANGANESE.

PMID- 16654420
TI  - SOME RESPONSES OF YOUNG CORN PLANTS TO MALEIC HYDRAZIDE.

PMID- 16654421
TI  - A TECHNIQUE FOR GROWING PLANTS UNDER STERILE CONDITIONS.

PMID- 16654422
TI  - A TECHNIQUE FOR THE CULTIVATION OF HIGHER PLANTS UNDER STERILE CONDITIONS.

PMID- 16654423
TI  - THE EFFECT OF MALEIC HYDRAZIDE ON TOMATO PLANTS IN RELATION TO THEIR AGE AT THE
      TIME OF TREATMENT.

PMID- 16654424
TI  - NOTES.

PMID- 16654425
TI  - The Amino Acid Composition and Distribution of N in Soybean Root Nodules Supplied
      N-Enriched N(2).

PMID- 16654426
TI  - Studies in Plant Carbonic Anhydrase. II. Kinetic Studies.

PMID- 16654427
TI  - Physiological and Morphological Responses of Barley to 2,4-Dichlorophenoxyacetic
      Acid.

PMID- 16654428
TI  - The Effect of Preharvest Foliar Sprays of Maleic Hydrazide on Sprout Inhibition
      and Storage Quality of Potatoes.

PMID- 16654429
TI  - The Absorption and Translocation Of 2,4-Dichlorophenoxyacetic Acid by Bean
      Plants.

PMID- 16654430
TI  - Brittleness and Other Responses of Corn to 2,4-Dichlorophenoxyacetic Acid.

PMID- 16654431
TI  - Nitrogen and Amino Acids in Normal, Habituated, and Bacteria-Free Crown Gall
      Tumor Tissue Cultures of Grape.

PMID- 16654432
TI  - Stimulation of Seedling Growth by Seed Treatments with N-Phenyl Succinimide
      Derivatives.

PMID- 16654433
TI  - Investigation on Injury to Plants from Air Pollution in the Los Angeles Area.

PMID- 16654434
TI  - Percentage of Carbohydrates in Kernels of Station Reid Yellow Dent Corn at
      Several Stages of Development.

PMID- 16654435
TI  - Ionic Accumulation in Citrus as Influenced by Rootstock and Scion and
      Concentration of Salts and Boron in the Substrate.

PMID- 16654436
TI  - Iron-Containing Frit as a Nutriculture Medium.

PMID- 16654437
TI  - The Influence of the Green Mesophyll in Stomatal Movement.

PMID- 16654438
TI  - Albinism Induced by Substituted Benzoic Acids.

PMID- 16654440
TI  - Notes.

PMID- 16654439
TI  - The Hill Reaction: Development of Chloroplast Activity During Greening of
      Etiolated Barley Leaves.

PMID- 16654441
TI  - The Action Spectrum for the Photochemical Evolution of Oxygen by Isolated
      Chloroplasts.

PMID- 16654442
TI  - Relationships of Certain Nutrients, Metabolites, and Inhibitors to Growth in the
      Avena Coleoptile.

PMID- 16654443
TI  - An Improved Electrical Conductivity Method for Accurately Following Changes in
      the Respiratory Quotient of a Single Biological Sample.

PMID- 16654444
TI  - Influence of Storage Temperature on Carotene, Total Carotenoids and Ascorbic Acid
      Content of Sweetpotatoes.

PMID- 16654445
TI  - The Behavior of Isocitric Acid in Excised Leaves of Bryophyllum Calycinum During
      Culture in Alternating Light and Darkness.

PMID- 16654446
TI  - Some Factors Affecting Nectar Secretion in Red Clover.

PMID- 16654447
TI  - Molybdenum Requirement of Leguminous Plants Supplied with Fixed Nitrogen.

PMID- 16654448
TI  - The Formation of Starch in Leaves of Bryophyllum Calycinum Cultured in Darkness.

PMID- 16654449
TI  - Metabolism of Infiltrated Organic Acids by Tobacco Leaves.

PMID- 16654450
TI  - Electrical and Curvature Responses of the Avena Coleoptile to Unilateral
      Illumination.

PMID- 16654451
TI  - Genetic and Chlorophyll Studies of a Yellow-Green Mutant in Muskmelon.

PMID- 16654452
TI  - Effect of Petroleum Oil Spray on Photosynthesis and Respiration in Citrus Leaves.

PMID- 16654453
TI  - The Osmotic Change during Auxin-Induced Water Uptake by Potato Tissue.

PMID- 16654454
TI  - Surface Activity as Related to Physiological Activity of Plant Growth-Regulators.

PMID- 16654455
TI  - Metabolism of 2,4-Dichlorophenoxyacetic Acid. I. CO(2) Production by Bean Plants
      Treated with Labeled 2,4-Dichlorophenoxyacetic Acids.

PMID- 16654456
TI  - Frenching Symptoms Produced in Nicotiana Tabacum and Nicotiana Rustica with
      Optical Isomers of Isoleucine and Leucine and with Bacillus Cereus Toxin.

PMID- 16654457
TI  - Varietal Root and Top Regeneration of Fig Cuttings as Influenced by the
      Application of Indolebutyric Acid.

PMID- 16654458
TI  - Measurement of Metabolic Gas Exchange with a Recording Mass Spectrometer.

PMID- 16654459
TI  - Nitrogen and Phosphorus Fractions, Respiration, and Structure of Normal and Crown
      Gall Tissues of Tomato.

PMID- 16654460
TI  - Pre- and Post-Harvest Changes in Carotene, Total Carotenoids and Ascorbic Acid
      Content of Sweetpotatoes.

PMID- 16654461
TI  - Absorption Spectra of Leaves. I. The Visible Spectrum.

PMID- 16654462
TI  - The Role of Ortho-Substitution in the Synthetic Auxins.

PMID- 16654463
TI  - Further Studies in the Simplification of Equipment for Subirrigation Experiments
      in Plant Nutrition.

PMID- 16654464
TI  - Relationship of the Cobalt and Light Effects on Expansion of Etiolated Bean Leaf
      Disks.

PMID- 16654465
TI  - Light Absorption by Chlorophyll at High Concentrations.

PMID- 16654466
TI  - The Effect of Hypocotyl Temperature on Translocation of Carbohydrates from Bean
      Leaves.

PMID- 16654468
TI  - Notes.

PMID- 16654467
TI  - The Biosynthesis of Carbon-14-Labeled Compounds. II. The Chromatographic
      Separation of the Monosaccharides, Disaccharides, and Trisaccharides from Plant
      Extracts.

PMID- 16654469
TI  - THE UPTAKE OF PHOSPHORUS BY BEAN PLANTS WITH PARTICULAR REFERENCE TO THE EFFECTS
      OF IRON.

PMID- 16654470
TI  - THE MECHANISM OF THE TETRAZOLIUM REACTION IN CORN EMBRYOS.

PMID- 16654471
TI  - A KINETIC STUDY OF THE ABSORPTION OF ALKALI CATIONS BY BARLEY ROOTS.

PMID- 16654472
TI  - A COMPARATIVE STUDY OF GRADUAL AND ABRUPT CHANGES IN ROOT TEMPERATURE ON WATER
      ABSORPTION.

PMID- 16654473
TI  - THE PERMEABILITY OF NON-STOMATE LEAF EPIDERMIS TO CARBON DIOXIDE.

PMID- 16654474
TI  - THE MEASUREMENT OF OXIDATION-REDUCTION POTENTIALS OF COTTONSEED SLURRIES.

PMID- 16654475
TI  - THE RELATION OF ACIDS AND PEROXIDES IN SPRAY OILS TO THE RESPIRATION OF SPRAYED
      BEAN LEAVES AND THE DEVELOPMENT OF INJURY.

PMID- 16654476
TI  - INHIBITION OF GROWTH BY BENZENE HEXACHLORIDE ISOMERS AND PROTECTIVE EFFECT OF
      GLUCOSE AS MEASURED BY CELL COUNTING TECHNIQUE.

PMID- 16654477
TI  - FIBER PROPERTIES AND CARBOHYDRATE AND NITROGEN LEVELS OF COTTON PLANTS AS
      INFLUENCED BY MOISTURE SUPPLY AND FRUITFULNESS.

PMID- 16654478
TI  - A CRITICAL STUDY OF THE COBALT CHLORIDE METHOD OF MEASURING TRANSPIRATION.

PMID- 16654479
TI  - THE EFFECT OF LIGHT AND NITROGEN LEVELS ON GROWTH AND ALKALOID CONTENT OF YOUNG
      PLANTS OF CINCHONA LEDGERIANA.

PMID- 16654480
TI  - THE EFFECT OF CALCIUM ON THE ABSORPTION OF POTASSIUM BY BARLEY ROOTS.

PMID- 16654481
TI  - EFFECTS OF LIGHT ON ELONGATION AND BRANCHING IN PEA ROOTS.

PMID- 16654482
TI  - ABSORPTION AND TRANSLOCATION OF RADIOACTIVE 2,4-DICHLORO-5-IODO-PHENOXYACETIC
      ACID BY GREEN PLANTS.

PMID- 16654483
TI  - CATALASE-CHLOROPHYLL RELATIONSHIP IN BARLEY SEEDLINGS.

PMID- 16654484
TI  - GROWTH REGULATING PROPERTIES OF SOME THIOSEMICARBAZONES.

PMID- 16654485
TI  - INCREASING THE SIZE OF THOMPSON SEEDLESS GRAPES BY MEANS OF 4-CHLOROPHENOXYACETIC
      ACID, BERRY THINNING AND GIRDLING.

PMID- 16654486
TI  - THE EFFECT OF INTERMITTENTLY VARIED PETIOLE TEMPERATURE ON CARBOHYDRATE
      TRANSLOCATION FROM BEAN LEAVES.

PMID- 16654487
TI  - TEMPERATURE RESPONSE OF FUNGI AS A STRAIGHT LINE TRANSFORMATION.

PMID- 16654490
TI  - NOTES.

PMID- 16654488
TI  - EFFECT OF 2,4-DICHLOROPHENOXYACETIC ACID ON PROTEOLYTIC ACTIVITY OF RED KIDNEY
      BEAN PLANTS.

PMID- 16654489
TI  - PHOTOPERIODIC RESPONSE OF LESPEDEZA.

PMID- 16654491
TI  - ENZYMATIC ACTIVITIES AS INDICATIONS OF COPPER AND IRON DEFICIENCIES IN PLANTS.

PMID- 16654492
TI  - LONGITUDINAL GRADIENTS OF P ABSORPTION IN ROOTS.

PMID- 16654494
TI  - EFFECT OF AGE OF LEAVES UPON THE RATE OF PHOTOSYNTHESIS IN SOME CONIFERS.

PMID- 16654495
TI  - THE RELATIVE RATES OF PHOTOSYNTHETIC ASSIMILATION OF ISOTOPIC FORMS OF CARBON
      DIOXIDE.

PMID- 16654493
TI  - THE DISTRIBUTION IN HIGHER PLANTS OF TRIPHOSPHOPYRIDINE NUCLEOTIDE-LINKED ENZYME
      SYSTEMS CAPABLE OF REDUCING GLUTATHIONE.

PMID- 16654496
TI  - TEMPERATURE OF POTATO AND TOMATO LEAVES.

PMID- 16654497
TI  - MALONIC ACID AS AN INHIBITOR OF MAIZE ROOT RESPIRATION.

PMID- 16654499
TI  - PREMATURE BLOSSOMING: EFFECTS OF VERNALIZATION, SEEDLING AGE AND ENVIRONMENT ON
      SUBSEQUENT GROWTH AND FLOWERING OF TRANSPLANTED TOBACCO.

PMID- 16654498
TI  - ASCORBIC ACID FORMATION IN POTATO TUBER SLICES.

PMID- 16654501
TI  - SOME RELATIONSHIPS BETWEEN XEROPHYTISM AND THE CONTENT OF RESIN,
      NORDIHYDROGUAIARETIC ACID AND PROTEIN OF LARREA DIVARICATA CAV.

PMID- 16654500
TI  - COMPOSITIONAL AND PHYSIOLOGICAL CHANGES ASSOCIATED WITH THE CHEMICAL DEFOLIATION
      OF COTTON.

PMID- 16654503
TI  - A RELATIONSHIP BETWEEN PHOTOPERIODISM AND RESPIRATION.

PMID- 16654502
TI  - PHYSIOLOGICAL CHANGES AND FREEZING INJURY IN MATURING MAIZE.

PMID- 16654504
TI  - SOME EFFECTS OF ARTIFICIAL DRYING OF CORN GRAIN.

PMID- 16654505
TI  - EFFECT OF 2,4-DICHLOROPHENOXYACETIC ACID ON MERISTEMATIC TISSUES OF CORN.

PMID- 16654506
TI  - SOME EFFECTS OF ZINC ON SEVERAL SPECIES OF GOSSYPIUM L.

PMID- 16654507
TI  - THE EFFECT OF DIFFERENT TISSUE PRETREATMENTS ON THE PHYSICO-CHEMICAL PROPERTIES
      OF EXPRESSED PLANT SAP.

PMID- 16654508
TI  - THE USE OF CHROMOTROPIC ACID FOR THE QUANTITATIVE DETERMINATION OF 2,4
      DICHLOROPHENOXYACETIC ACID.

PMID- 16654509
TI  - EXTRACELLULAR PHOTOSYNTHETIC REACTIONS. II. IDENTIFICATION OF RADIOACTIVE MALATE.

PMID- 16654510
TI  - DIORTHO SUBSTITUTED PHENOXYACETIC ACIDS AS ANTIAUXINS.

PMID- 16654512
TI  - EUGENE CURTIS AUCHTER 1889-1952.

PMID- 16654511
TI  - NOTES.

PMID- 16654513
TI  - Influence of Visible and Near Infrared Radiant Energy on Organ Development and
      Pigment Synthesis in Bean and Corn.

PMID- 16654514
TI  - Filters for the Isolation of Narrow Regions in the Visible and Near-Visible
      Spectrum.

PMID- 16654515
TI  - Phosphogluconic Dehydrogenase in Higher Plants.

PMID- 16654516
TI  - Frenching of Ragweed (Ambrosia artemisiifolia L.).

PMID- 16654517
TI  - Effect of Stable Boron Isotopes on Growth of Tobacco in Solution Cultures.

PMID- 16654518
TI  - Low Temperature Inductions of Flowering in a Nicotiana rustica X N. tabacum
      Hybrid.

PMID- 16654519
TI  - The Effect of 2,4-Dichlorophenoxyacetic Acid on Phosphorylase, Phosphatase,
      Amylase, Catalase, and Peroxidase Activity in Wheat.

PMID- 16654520
TI  - Optimum Chloride Concentration for Malt Diastase Activity as a Function of
      Temperature.

PMID- 16654522
TI  - Notes.

PMID- 16654521
TI  - An Autoradiographic Technique for Detailed Studies with Plant Tissue.

PMID- 16654523
TI  - Studies on the Chemistry of the Living Bark of the Black Locust in Relation to
      Its Frost Hardiness. III. The Validity of Plasmolysis and Desiccation Tests for
      Determining the Frost Hardiness of Bark Tissue.

PMID- 16654524
TI  - The Sprouting of Sweetgum in Relation to Season of Cutting and Carbohydrate
      Content.

PMID- 16654525
TI  - The Physiological Action of Smog on Plants. I. Initial Growth and Transpiration
      Studies.

PMID- 16654526
TI  - Some Respiratory Characteristics of the Blue-Green Alga, Anabaena.

PMID- 16654527
TI  - The Metabolism of Foliar-Applied Urea. I. Relative Rates of CO(2) Production by
      Certain Vegetable Plants Treated with Labeled Urea.

PMID- 16654528
TI  - The Relation of the Amino Acid Composition to the Development of Oats.

PMID- 16654529
TI  - Electrode Reactions of Isolated Chloroplast Fragments.

PMID- 16654530
TI  - Effect of Inorganic Ions and Their Conductances on Geotropic Curvature of the
      Avena Coleoptile.

PMID- 16654531
TI  - Effect of Quality and Intensity of Solar Radiation on Injury of Lemon Fruit by
      Sulphur Treatment in the Field.

PMID- 16654532
TI  - Studies on the Chemistry of the Living Bark of the Black Locust Tree in Relation
      to Frost Hardiness. IV. Effects of Ringing on Translocation, Protein Synthesis
      and the Development of Hardiness.

PMID- 16654533
TI  - Floral Induction and Development in Ochard Grass.

PMID- 16654534
TI  - On the Mechanism of Action of Growth Regulators.

PMID- 16654535
TI  - Pyridine Nucleotide-Nitrate Reductase from Extracts of Higher Plants.

PMID- 16654536
TI  - Carbohydrate Metabolism in the Tomato Fruit as Affected by Pollination,
      Fertilization and Application of Growth Regulators.

PMID- 16654537
TI  - Factors Affecting Cotyledonal Cracking during the Germination of Beans (Phaseolus
      Vulgaris).

PMID- 16654538
TI  - Accumulation and Distribution of Molybdenum in the Cotton Plant.

PMID- 16654539
TI  - The Use of C in Locating Growth Regions in the Cell Walls of Elongating Cotton
      Fibers.

PMID- 16654540
TI  - Phosphorylase and a Branching Enzyme in Squash.

PMID- 16654541
TI  - The Effects of Maleic Hydrazide on Flower Initiation.

PMID- 16654542
TI  - Preferential Assimilation of Ammonium Ion by Chlorella vulgaris.

PMID- 16654543
TI  - Reserve Carbohydrates in Orchard Grass Cut for Hay.

PMID- 16654544
TI  - The Intracellular Distribution of Ascorbic Acid in Turnip Leaves.

PMID- 16654545
TI  - Absence of Acid Phosphatase from Chloroplasts of Spinach and Iris.

PMID- 16654546
TI  - Symptoms of Molybdenum Deficiency in Tobacco.

PMID- 16654547
TI  - The Use of Seeds with Low Content of Trace Elements in Studies on Essentially of
      Micro-nutrients.

PMID- 16654548
TI  - Partial Separation of the Plastid Pigments by Paper Chromatography.

PMID- 16654549
TI  - The Distribution of C in the Root and Shoot Apices of Young Corn Plants.

PMID- 16654550
TI  - Water-cooled Lamp Systems with Refluxing Aqueous Filters.

PMID- 16654551
TI  - Notes.

PMID- 16654552
TI  - Kinetics of Auxin Interaction.

PMID- 16654553
TI  - The Diurnal Variation in the Translocation of Minerals across Bean Roots.

PMID- 16654554
TI  - Heavy-Metal Nutrition and Iron Chlorosis of Citrus Seedlings.

PMID- 16654555
TI  - Studies on the Chemistry of the Living Bark of the Black Locust in Relation to
      Its Frost Hardiness. V. Seasonal Transformations and Variations in the
      Carbohydrates: Starch-Sucrose Interconversions.

PMID- 16654556
TI  - Investigations of Nitrogen Compounds and Nitrogen Metabolism in Plants. Iii.
      gamma-Aminobutyric Acid in Plants, With Special Reference to the Potato Tuber and
      a New Procedure for Isolating Amino Acids Other Than alpha-Amino Acids.

PMID- 16654557
TI  - An Atypical Growth of Cabbage Seedling Roots. Iii. Tissue Culture and
      Physiological Comparisons of Typical and Atypical Roots.

PMID- 16654558
TI  - Some Relationships of Sterols to Plant Growth.

PMID- 16654559
TI  - The Effect of Sodium Trichloroacetate upon the Metabolism of Wheat Seedlings
      (Triticum Vulgare L.).

PMID- 16654560
TI  - Auxin Relations of a Dwarf Pea.

PMID- 16654561
TI  - The Role of Boron in the Translocation of Sucrose.

PMID- 16654562
TI  - Changes in the Carbohydrate Reserves of Ladino White Clover Following
      Defoliation.

PMID- 16654563
TI  - Bolting and Flowering of Sugar Beets in Continuous Darkness.

PMID- 16654564
TI  - Comparative Stimulation of Parthenocarpy in the Tomato by Various Indole
      Compounds.

PMID- 16654565
TI  - Iron and Copper Enzymes in Leaf Lamina of Tobacco When Deficient in
      Micronutrients or Grown on Calcareous and Organic Soils.

PMID- 16654566
TI  - The Effect of the Dominance of a Metabolic System Requiring Iron or Copper on the
      Development of Lime-Induced Chlorosis.

PMID- 16654567
TI  - Relationship of Seasonal Trends in Carbohydrate and Nitrogen Levels and Effects
      of Girdling and Spraying with Sucrose and Urea to the Nutritional Interpretation
      of Boll Shedding in Cotton.

PMID- 16654568
TI  - The Climacteric Rise in Fruit Respiration as Controlled by Phosphorylative
      Coupling.

PMID- 16654569
TI  - Distribution of Total Soluble Solids, Ascorbic Acid, Total Acid, and Bromelin
      Activity in The Fruit of the Natal Pineapple (Ananas Comosus L. MERR.).

PMID- 16654570
TI  - The Composition of Plant Fractions Extracted with 80% Alcohol.

PMID- 16654571
TI  - Nitrate Reduction by Chlorella.

PMID- 16654572
TI  - Bioelectric Potentials of Tumor-Infected Plants.

PMID- 16654573
TI  - Carotenoids in Grapefruit, Citrus Paradisi.

PMID- 16654574
TI  - Notes.

PMID- 16654575
TI  - The Physical Environment and Oxidative and Phosphorylative Capacities of Higher
      Plant Mitochondria.

PMID- 16654576
TI  - The Absorption and Translocation of Iron.

PMID- 16654577
TI  - The Absorption and Translocation of Strontium by Plants.

PMID- 16654578
TI  - Concentration and Translocation of Nitrogen Compounds in the Corn Plant (Zea
      Mays) During Grain Development.

PMID- 16654579
TI  - Inhibition of Auxin Effects by 2,4,6-Trichlorophenoxyacetic acid.

PMID- 16654580
TI  - Studies on the Chemistry of the Living Bark of the Black Locust Tree in Relation
      to Frost. VI. Amylase and Phosphorylase Systems of the Bark Tissues.

PMID- 16654581
TI  - The Influence of Soil Physical Condition During the Flowering Period on Nectar
      Production in Snapdragon.

PMID- 16654582
TI  - The Effect of Magnesium Concentration on Chlorophyll and Catalase Development in
      Chlorella.

PMID- 16654583
TI  - The Effect of Magnesium Concentration on Growth of Chlorella.

PMID- 16654584
TI  - Aluminum Toxicity Studies with Radioactive Phosphorus.

PMID- 16654585
TI  - Formation of Esters by Yeast. II. Investigations with Cellular Suspensions of
      Hansenula Anomala.

PMID- 16654586
TI  - Further Evidence of Persistence Of the 2,4-D Stimulus in Cotton.

PMID- 16654587
TI  - Photosynthesis in the Potato Under Field Conditions.

PMID- 16654588
TI  - Absorption and Metabolism of Tritium Oxide and Tritium Gas by Bean Plants.

PMID- 16654589
TI  - Enzymatic Synthesis of Glutamine in Higher Plants.

PMID- 16654590
TI  - Enzymatic Synthesis of Gamma-Glutamyl-Cysteine in Higher Plants.

PMID- 16654591
TI  - The Biosynthesis of Carbon-14-Labeled Compounds. III. The Separation and
      Isolation of Sugars by Ion-exchange Chromatography.

PMID- 16654592
TI  - The Use of Cation-exchange Resins for the Hydrolysis of Sucrose in Plant
      Extracts.

PMID- 16654593
TI  - Conversion of C-Labeled Acetate to Citric and Malic Acids in the Tomato Fruit.

PMID- 16654594
TI  - A Technique for Removal of Aseptic Cylinders from Carrot Root.

PMID- 16654595
TI  - Pantothenic Acid and Acetic Acid Utilization in Tomato Fruit-set.

PMID- 16654596
TI  - Growth of Tobacco Seedlings with Nitrate and its Reduction Products.

PMID- 16654598
TI  - Notes.

PMID- 16654597
TI  - Responses of Plants to Rhenium.

PMID- 16654599
TI  - The Metabolism of Nitrogenous Compounds by Sunflower Crown Gall Tissue Cultures.

PMID- 16654600
TI  - The Inhibiting Effect of Root Tips on the Elongation of Excised Pisum Epicotyls
      Cultured in Vitro.

PMID- 16654601
TI  - Leaf and Air Temperatures under Freezing Conditions.

PMID- 16654602
TI  - Some Observations on the Reduction of 2,3,5-Triphenyltetrazolium Chloride in
      Plant Tissue as Influenced by Mineral Nutrition.

PMID- 16654603
TI  - The Extraction and Colorimetric Estimation of Indole-3-Acetic Acid and Its Esters
      in Developing Corn Kernels.

PMID- 16654605
TI  - Auxin Inactivation and Its Relation to Leaf Drop Caused by the Fungus Omphalia
      Flavida.

PMID- 16654606
TI  - Direct Chemical Proof of Ethylene Production by Detached Leaves.

PMID- 16654607
TI  - Metabolism of Sucrose and Related Oligosaccharides by Spores of the Fungus
      Myrothecium Verrucaria.

PMID- 16654608
TI  - Peanut and Oil Palm Foliar Diagnosis Interrelations of N, P, K, Ca, Mg.

PMID- 16654609
TI  - The Respiration of the Pea Plant. Oxidation of Hexose Phosphate and Pentose
      Phosphate by Cell-free Extracts of Pea Leaves.

PMID- 16654610
TI  - Effects of Shade and Partial Defoliation on Carbohydrate Levels and the Growth,
      Fruiting and Fiber Properties of Cotton Plants.

PMID- 16654611
TI  - Respiration of Maize Grain.

PMID- 16654612
TI  - Studies in Plant Metabolism. III. Absorption, Translocation and Metabolism of
      Radioactive 2,4-D in Corn and Wheat Plants.

PMID- 16654613
TI  - Inhibition of Growth of Chlorella Pyrenoidosa by Beta-emitting Radioisotopes.

PMID- 16654614
TI  - Effect of 2,4-Dichlorophenoxyacetic Acid on Photosynthesis and Respiration.

PMID- 16654615
TI  - Organic Acid Metabolism and Ion Absorption in Roots.

PMID- 16654616
TI  - Zinc Content of Bean Plants in Relation to Deficiency Symptoms and Yield.

PMID- 16654617
TI  - The Influence of Cobalt and Sugars upon the Elongation of Etiolated Pea Stem
      Segments.

PMID- 16654618
TI  - Applicability of Poiseuille'S Law to Exudation of Oleoresin from Wounds on Slash
      Pine.

PMID- 16654619
TI  - The Effects of Three Levels of Magnesium on the Nutrient-Element Composition of
      two Inbred Lines of Corn and on their Susceptibility to Helminthosporium Maydis.

PMID- 16654620
TI  - Auxin Relationships of the Rice Coleoptile.

PMID- 16654621
TI  - An Improved Infiltration Series for Studying Stomatal Opening as Illustrated with
      Coffee.

PMID- 16654622
TI  - Studies on the Nitrogenous Nutrition of Rice.

PMID- 16654624
TI  - Seed Vitality and Other Cotton Characters as Affected by the Age of Seed.

PMID- 16654623
TI  - The Estimation of Dehydrogenases in Plant Tissue.

PMID- 16654625
TI  - Vitamin Content of Turnip-green Plants in Relation to Growth.

PMID- 16654626
TI  - The Effect of Temperature on the Conversion of Protochlorophyll to Chlorophyll a
      in Etiolated Barley Leaves.

PMID- 16654627
TI  - The Development of Chlorophyll and Oxygen-evolving Power in Etiolated Barley
      Leaves When Illuminated.

PMID- 16654628
TI  - Measurement of Algal Growth under Controlled Steady-state Conditions.

PMID- 16654629
TI  - Growth Rate of Chlorella in Flashing Light.

PMID- 16654630
TI  - Recording Oxidation-reduction Potentials in Plant Preparations.

PMID- 16654631
TI  - Studies on the Photosynthetic Reaction. II. Sodium Formate and Urea Feeding
      Experiments with Nostoc muscorum.

PMID- 16654632
TI  - Fruit Respiration and Ethylene Production.

PMID- 16654633
TI  - The Effect of X-Rays on Uptake and Loss of Ions by Potato Tuber Tissue.

PMID- 16654634
TI  - The Effect of Light on the Oxygen Metabolism of the Photosynthetic Bacterium,
      Rhodospirillum rubrum.

PMID- 16654635
TI  - Fluctuations in Sensitivity of the Avena Test Due to Air Pollutants.

PMID- 16654636
TI  - A Light Activated Accumulation of Niacin in Tomato Leaf Discs.

PMID- 16654637
TI  - B Vitamins in Starchy and Sugary Maize Endosperms.

PMID- 16654638
TI  - Thicker Aleurone Inadequate Explanation for Higher Niacin in Sugary Maize.

PMID- 16654639
TI  - A Device for Continuous Aeration and Nutrient Renewal of Entire Plants under
      Sterile Conditions.

PMID- 16654641
TI  - A Simple Demonstration of Some Properties of Capillaries.

PMID- 16654640
TI  - Fixation of N(2) by Excised Nodules.

PMID- 16654642
TI  - An Energy Dependent Incorporation of Amino Acids into the Protein of Plant
      Mitochondria.

PMID- 16654643
TI  - INSERTION TO DISCUSSION, PAGE 186, OF THE ARTICLE BY HULL, WENT, AND YAMADA.

PMID- 16654644
TI  - The Growth and Inorganic Nutrition of Scenedesmus obliquus in Mass Culture.

PMID- 16654645
TI  - Some Effects of Deuterium Oxide on the Quinone Hill Reaction of Chlorella
      pyrenoidosa Chick.

PMID- 16654646
TI  - The Interrelation between CO(2) Metabolism and Photoperiodism in Kalanchoe.

PMID- 16654647
TI  - The Absorption of Inorganic Ions by Chlorella pyrenoidosa.

PMID- 16654648
TI  - The Influence of Hydrogen Ion Concentration on Cation Absorption by Barley Roots.

PMID- 16654649
TI  - On the Biosynthesis of Carotenoids.

PMID- 16654650
TI  - Causes of Injury to Flooded Tobacco Plants.

PMID- 16654651
TI  - Subcooling and Ice Nucleation in Lemons.

PMID- 16654652
TI  - The Relative Sensitivity of Xanthium Leaves of Different Ages to Photoperiodic
      Induction.

PMID- 16654653
TI  - Carbohydrate Metabolism and Oxalic Acid Synthesis by Botrytis cinerea.

PMID- 16654654
TI  - Nature and Distribution of Glycolic Acid Oxidase in Plants.

PMID- 16654655
TI  - The Oxidation of Reduced Diphosphopyridine Nucleotide by an Ascorbate System from
      Cucumber.

PMID- 16654656
TI  - The Proteins of Green Leaves. VI. Centrifugal Fractionation of Tobacco Leaf
      Homogenates and Some Properties of Isolated Chloroplasts.

PMID- 16654657
TI  - The Role of Vitamins and Micronutrient Elements in the Nutrition of the Apical
      Meristem of Pea Roots.

PMID- 16654658
TI  - Isolation of Carbon-14-labeled Sedoheptulose and Other Products from Sedum
      spectabile.

PMID- 16654660
TI  - The Electrophoretic Behavior of Lignin.

PMID- 16654659
TI  - The Effect of Auxin on the Flowering Behaviour of Wintex Barley and Petkus Rye.

PMID- 16654662
TI  - Possible Interaction between Light-dark Cycles and Endogenous Daily Rhythms on
      the Growth of Tomato Plants.

PMID- 16654661
TI  - Diphosphopyridine Nucleotide-Nitrate Reductase from Soybean Nodules.

PMID- 16654663
TI  - Metabolism of 2,4-Dichlorophenoxyacetic Acid. III. Metabolism and Persistence in
      Dormant Plant Tissue.

PMID- 16654664
TI  - The Effect of Light Intensity on Photosynthetic Rate in Scotch Pine.

PMID- 16654665
TI  - Nomenclature of Chemical Plant Regulators: Report by a Committee of the American
      Society of Plant Physiologists.

PMID- 16654667
TI  - A Porphyrin Pigment from Photosensitive Non-chlorophyllous Plant Tissues.

PMID- 16654668
TI  - Position of C in Alcohol and Carbon Dioxide Formed from Labeled Glucose by Corn
      Root Tips.

PMID- 16654669
TI  - The Direct Oxidation Pathway in Plant Respiration.

PMID- 16654670
TI  - Investigation into the Function of Pyridoxin as a Growth Factor for Excised
      Tomato Roots.

PMID- 16654671
TI  - Studies on the Chemistry of the Living Bark of the Black Locust in Relation to
      Its Frost Hardiness. VII. A Possible Direct Effect of Starch on the
      Susceptibility of Plants to Freezing Injury.

PMID- 16654672
TI  - The Availability of Magnesium from Organic Carriers in Artificial Substrates.

PMID- 16654673
TI  - Translocation of Radioactive Isotopes from Various Regions of Roots of Barley
      Seedlings.

PMID- 16654674
TI  - Effect of Differential Nitrogen, Potassium, and Magnesium Supply to Young
      Valencia Orange Trees in Sand Culture on Mineral Composition Especially of Leaves
      and Fibrous Roots.

PMID- 16654675
TI  - The Influence of Mineral Nutrition on the Organic Acids of the Tomato,
      Lycopersicum esculentum.

PMID- 16654676
TI  - Nitrogenous Constituents of Sap Exuded from the Sapwood of Acer saccharum.

PMID- 16654677
TI  - Studies in Plant Metabolism. IV. Comparative Effects of 2,4-Dichlorophenoxyacetic
      Acid and Other Plant Growth Regulators on Phosphorus Metabolism in Bean Plants.

PMID- 16654678
TI  - Promotion by Zinc of the Formation of Cytochromes in Ustilago sphaerogena.

PMID- 16654679
TI  - Auxin Physiology in Bean Leaf Stalks.

PMID- 16654680
TI  - Incorporation of Radioactive Glutamic Acid into the Proteins of Higher Plants.

PMID- 16654681
TI  - The Effect of Temperature on the Behavior of Malic Acid and Starch in Leaves of
      Bryophyllum calycinum Cultured in Darkness.

PMID- 16654682
TI  - Smog Injury and Rust Infection.

PMID- 16654683
TI  - Precursor Relationships in Light Activated Accumulation of Niacin in Leaf Disks
      from Normal, Light-starved, and Zinc Deficient Tomato Plants.

PMID- 16654684
TI  - Assay of Cytochrome Oxidase Activity of Sunflower Leaf Tissue in Relation to pH
      Value and Cation Concentration of the Buffer.

PMID- 16654685
TI  - The Effect of Carbon Monoxide on Respiration in Higher Plants.

PMID- 16654686
TI  - Nomenclature of Chemical Plant Regulators-A Criticism.

PMID- 16654687
TI  - The Occurrence of Coenzyme A in Plants.

PMID- 16654688
TI  - Studies on the Chemistry of the Living Bark of the Black Locust in Relation to
      its Frost Hardiness. VIII. Possible Enzymatic Processes Involved in Starch
      Sucrose Interconversions.

PMID- 16654689
TI  - The Interrelation between CO(2) Metabolism and Photoperiodism in Kalanchoe. II.
      Effect of Prolonged Darkness and High Temperatures.

PMID- 16654690
TI  - Some Physiological Characteristics of Ascospore Activation in Neurospora crassa.

PMID- 16654691
TI  - Effect Of Scald On Apple Skin Respiration.

PMID- 16654692
TI  - A Study of Chlorophyll in a White Mutant Strain of Helianthus annuus.

PMID- 16654693
TI  - The Dark Fixation of Carbon Dioxide as a Factor in Photoperiodism.

PMID- 16654694
TI  - Changes in Free Auxin Content during the Photoinduction of Short-day Plants.

PMID- 16654695
TI  - Seasonal and Diurnal Changes in the Water Contents and Water Deficits of Bartlett
      Pear Leaves.

PMID- 16654696
TI  - The Physical Environment of Chloroplasts as Related to their Morphology and
      Activity in Vitro.

PMID- 16654697
TI  - The Terminal Respiratory Enzymes in Neurospora Tetrasperma.

PMID- 16654698
TI  - Effect of Light on the Formation of a Pigment in the Tomato Fruit Cuticle.

PMID- 16654699
TI  - Photosynthesis in Chlorella during Intermittent Illumination of Long Periodicity.

PMID- 16654700
TI  - Phosphorus Nutrition of Soybeans.

PMID- 16654701
TI  - The Effect of Volatile Substances Released by Soil, Humus, and Composts on the
      Growth of Excised Roots.

PMID- 16654703
TI  - Calcium and Magnesium in Citrus Seeds.

PMID- 16654702
TI  - Differences in Survival of Excised Ponderosa Pine Leaves of Various Ages.

PMID- 16654704
TI  - The Immediate Effect of Severing on the Photosynthetic Rate of Norway Spruce
      Branches.

PMID- 16654706
TI  - Turbidimetric Determination of Dry Weight of Algae.

PMID- 16654705
TI  - The Influence of 2,4-Dichlorophenoxyacetic Acid on the Phosphorus Metabolism of
      Cranberry Bean Plants (Phaseolus vulgaris).

PMID- 16654708
TI  - Dehydrogenase Activity and Respiration; a Quantitative Comparison.

PMID- 16654709
TI  - The Carbon Dioxide Content of Field Air.

PMID- 16654710
TI  - A Developmental Study of D-Glyceric Acid Dehydrogenase.

PMID- 16654711
TI  - Partial Reactions in the Formation of the Floral Stimulus in Xanthium.

PMID- 16654712
TI  - Some Effects of Ethanol Extracts of Potatoes on the Activity of a Phosphorylase
      Preparation.

PMID- 16654714
TI  - Chlorine-A Micronutrient Element for Higher Plants.

PMID- 16654713
TI  - The Effect of Abnormally Prolonged Alternating Periods of Light and Darkness upon
      the Composition of Bryophyllum calycinum Leaves.

PMID- 16654715
TI  - Growth Inhibitor Activity in Xanthium in Relation to Photoperiodism.

PMID- 16654716
TI  - The Flowering of Sunflower Explants in Aseptic Culture.

PMID- 16654717
TI  - Studies in Plant Metabolism. IV. Comparative Effects of 2,4-Dichlorophenoxyacetic
      Acid and Other Plant Growth Regulators on Phosphorus Metabolism in Bean Plants
      (Continued).

PMID- 16654719
TI  - Address to the American Society of Plant Physiologists.

PMID- 16654720
TI  - The Properties of Janus Green B as a Hill Oxidant.

PMID- 16654721
TI  - Photocontrol of Lepidium Seed Germination.

PMID- 16654722
TI  - Inhibition of Ion Absorption and Respiration in Barley Roots.

PMID- 16654723
TI  - The Effect of Different Iron and Manganese Nutrient Levels on the Catalase and
      Cytochrome Oxidase Activities of Green and Albino Sunflower Leaf Tissues.

PMID- 16654724
TI  - Free Auxins and Free Tryptophane in the Strawberry.

PMID- 16654725
TI  - Changes in Nitrogen Fractions and Proteolytic Enzymes of Soybean Plants Treated
      with 2,4-Dichlorophenoxyacetic Acid.

PMID- 16654726
TI  - The Calcium and Potassium Nutrition of Cotton as Influenced by Sodium.

PMID- 16654727
TI  - Studies on an Enzyme System from Wheat Germ Catalyzing the Aerobic Oxidation of
      Reduced Triphosphopyridine Nucleotide.

PMID- 16654728
TI  - Fat Metabolism in Higher Plants. III. Enzymatic Oxidation of Glycerol.

PMID- 16654729
TI  - The Enzymatic Oxidation of Ascorbic Acid in the Slime Mold, Physarum
      Polycephalum.

PMID- 16654730
TI  - Oxidation of 2,3',6-Trichloroindophenol by the Lipoxidase System.

PMID- 16654731
TI  - Influence of pH On 2,4-Dichlorophenoxyacetic and Acetic Acid Activity in
      Chlorella.

PMID- 16654732
TI  - Changes in the Activities of Several Enzymes during Germination and Seedling
      Development in Corn (Zea mays L.).

PMID- 16654733
TI  - The Isolation of Plant Cuticle with Pectic Enzymes.

PMID- 16654734
TI  - Studies on the Mineral Nutrition of Cassava (Manihot Utilissima Pohl.).

PMID- 16654735
TI  - A Rapid, Postillumination Deceleration of Respiration in Green Leaves.

PMID- 16654736
TI  - Effect of Boron Deficiency on Nicotine Formation in Tobacco.

PMID- 16654737
TI  - The Role of 2,4-Dichlorophenol in the Destruction of Indoleacetic Acid by
      Peroxidase.

PMID- 16654739
TI  - The Relation of External Rubidium Concentration to Amounts and Rates of Uptake by
      Excised Potato Tuber Tissue.

PMID- 16654740
TI  - Nitrogen Metabolism in Scenedesmus as Affected by Environmental Changes.

PMID- 16654741
TI  - Effects of Micronutrient Deficiencies on Mineral Composition, Nitrogen Fractions,
      Ascorbic Acid and Burn of Tobacco Grown to Flowering in Water Culture.

PMID- 16654742
TI  - Silicon Metabolism in Diatoms. II. Sources of Silicon for Growth of Navicula
      Pelliculosa.

PMID- 16654743
TI  - Role of Molybdenum as a Constituent of Nitrate Reductase from Soybean Leaves.

PMID- 16654744
TI  - Purification of Chloroplasts by a Density Technique.

PMID- 16654745
TI  - Enzymatic Auxin Inactivation by Extracts of the Fern, Osmunda cinnamomea L.

PMID- 16654746
TI  - A Comparison of Auxin Destruction by Tissue Extracts and Intact Tissues of the
      Fern, Osmunda cinnamomea L.

PMID- 16654747
TI  - Effects of Oxygen and Carbon Dioxide Levels upon Absorption of Potassium by
      Plants.

PMID- 16654748
TI  - Inhibition of Excised Tomato Roots by Sulfanilamide and Its Reversal by P
      Aminobenzoic Acid and N-Pteroylglutamic Acid.

PMID- 16654749
TI  - The Distribution of Rutin and Other Flavonoid Substances in Buckwheat Seedlings.

PMID- 16654750
TI  - Ascorbic Acid Oxidase in Barley Roots.

PMID- 16654751
TI  - Determination of Fe in Plant Material by the Thiocyanate Method.

PMID- 16654752
TI  - Translocation from Soybean Leaves, II.

PMID- 16654753
TI  - Oxidation and Decarboxylation of Amino Acids by Squash Preparations.

PMID- 16654755
TI  - The Rise of Sap in Tall Grapevines.

PMID- 16654756
TI  - Ionic Species in Orthophosphate Absorption by Barley Roots.

PMID- 16654757
TI  - Studies on the Mechanism of Phytohormone Damage by Ionizing Radiation. I. The
      Radiosensitivity of Indoleacetic Acid.

PMID- 16654758
TI  - The Correlation of Different Aspects of Auxin Action.

PMID- 16654759
TI  - Calcium-Magnesium Nutrition with Special Reference to Serpentine Soils.

PMID- 16654760
TI  - Effects of Ultraviolet Radiation and Calcium and Their Interaction on Salt
      Absorption by Excised Mung Bean Roots.

PMID- 16654761
TI  - On the Nature of the Enzymatically Catalyzed Oxidation Products of Indoleacetic
      Acid.

PMID- 16654762
TI  - Identification of the Carbon Dioxide Burst in Chlorella Using the Recording Mass
      Spectrometer.

PMID- 16654763
TI  - Fat Metabolism in Higher Plants. VI. Incorporation of P into Peanut Mitochondrial
      Phospholipids.

PMID- 16654764
TI  - The Development of Bean Seeds (Phaseolus vulgaris L.).

PMID- 16654765
TI  - Influence of Night Temperature and Nitrogen Nutrition on the Growth, Sucrose
      Accumulation and Leaf Minerals of Sugar Beet Plants.

PMID- 16654766
TI  - Comparative Physiology of Green and Albino Corn Seedlings.

PMID- 16654767
TI  - Carbon Dioxide Fixation and Ion Absorption in Barley Roots.

PMID- 16654768
TI  - Short-Time Fixation of Labelled Carbon Dioxide by Barley Leaves under Steady
      State Conditions.

PMID- 16654769
TI  - Studies in Plant Metabolism. V. the Metabolism of Radioactive 2,4-D in Etiolated
      Bean Plants.

PMID- 16654770
TI  - Photosynthesis and Respiration of Three Blue-Green Algae.

PMID- 16654771
TI  - Persistent Rhythms of O(2)-Consumption in Potatoes, Carrots and the Seaweed,
      Fucus.

PMID- 16654772
TI  - The Phosphorus-Iron Relationship in Genetical Chlorosis.

PMID- 16654774
TI  - Effect of Soil-Moisture Content on the Rate of Photosynthesis and Respiration in
      Ladino Clover (Trifolium Repens L.).

PMID- 16654775
TI  - A Study of the Role of the Hydrogen Ion in the Mechanism of Potassium Absorption
      by Excised Barley Roots.

PMID- 16654776
TI  - Cytochrome Oxidase Content and Respiratory Rates of Etiolated Wheat and Barley
      Seedlings.

PMID- 16654777
TI  - Effects of Polluted Atmospheres on Organic Acid Composition in Plant Tissues.

PMID- 16654778
TI  - Auxin-Antiauxin Interaction at High Auxin Concentrations.

PMID- 16654779
TI  - The Dual Role of Auxin in Flowering.

PMID- 16654780
TI  - Roles of Embryo and Endosperm in Determining Niacin Content of Starchy and Sugary
      Maize Endosperms.

PMID- 16654781
TI  - Relation of Respiratory and Enzymatic Activity to Corn Seed Viability.

PMID- 16654782
TI  - Glucose Dissimilation in the Higher Plant. Effect of Age of Tissue.

PMID- 16654783
TI  - Effect of Certain Metabolic Inhibitors on Translocation of P in Bean Plants.

PMID- 16654784
TI  - Incorporation of Radioactive Amino Acids into the Proteins of Plant Tissue
      Homogenates.

PMID- 16654785
TI  - Nonvolatile Organic Acids of Crown Galls, Crown Gall Tissue Cultures and Normal
      Stem Tissue.

PMID- 16654786
TI  - Effects of Sporulation Medium and Age on Fungus Spore Physiology.

PMID- 16654787
TI  - Studies on Nitrogen-Fixing Blue-Green Algae. I. Growth and Nitrogen Fixation by
      Anabaena Cylindrica Lemm.

PMID- 16654788
TI  - Conversion of Carbon-14-Labeled Urea into Amino Acids in Leaves.

PMID- 16654789
TI  - Bioassay of Mercury Vapor Arising from a Phenyl Mercury Compound.

PMID- 16654790
TI  - Incorporation of Radioactive Acetate and Sucrose into Amino Acids and Protein of
      Excised Organs of Red Kidney Bean.

PMID- 16654791
TI  - The Formation of Indoleacetylaspartic Acid in Pea Seedlings.

PMID- 16654792
TI  - Inhibition of Plant Growth by 2-Mercaptobenzimidazole Analogs.

PMID- 16654793
TI  - A Survey of the Nonvolatile Organic Acids in Seedlings of Some Grasses and
      Legumes.

PMID- 16654794
TI  - Transpiration and the Absorption and Distribution of Radioactive Phosphorus in
      Plants.

PMID- 16654795
TI  - Studies on Nitrite Metabolism in Higher Plants.

PMID- 16654796
TI  - Flower-Promoting Activity of Pea Seed Diffusates.

PMID- 16654798
TI  - Studies on the Enzymatic Synthesis of Glutamine.

PMID- 16654799
TI  - Succinoxidase and Cytochrome Oxidase in Barley Roots.

PMID- 16654800
TI  - Effects of Antimetabolites of Nucleic Acid Components on the Growth of Diplodia
      natalensis.

PMID- 16654801
TI  - Chlorophyll and Carotenoid Destruction in the Absence of Light in Seedlings of
      Zea Mays L.

PMID- 16654802
TI  - Respiration and Salt Absorption by Excised Barley Roots.

PMID- 16654803
TI  - The Histochemical Localization of Peroxidase in Roots and Its Induction by
      Indoleacetic Acid.

PMID- 16654804
TI  - Some Physiological Aspects of Bunt Resistance in Wheat.

PMID- 16654805
TI  - Studies on Cytochrome Reductase in Higher Plants.

PMID- 16654806
TI  - Riboflavin Synthesis by Epicotyls of White Lupine Seedlings Grown in Sterile
      Culture.

PMID- 16654807
TI  - The Influence of Rate of Cooling and Winter Cover on the Winter Survival of
      Ladino Clover and Alfalfa.

PMID- 16654808
TI  - Iron, the Limiting Element in a Chlorosis: Part I. Availability and Utilization
      of Iron Dependent upon Nutrition and Plant Species.

PMID- 16654809
TI  - Iron, the Limiting Element in a Chlorosis: Part II. Copper-Phosphorus Induced
      Chlorosis Dependent upon Plant Species and Varieties.

PMID- 16654810
TI  - Respiration of the Pea Plant. Metabolism of Hexose Phosphate and Triose Phosphate
      by Cell-free Extracts of Pea Roots.

PMID- 16654811
TI  - Photoreversibility of Leaf and Hypocotyl Elongation of Dark Grown Red Kidney Bean
      Seedlings.

PMID- 16654812
TI  - Interaction of Temperature and Light in Germination of Seeds.

PMID- 16654813
TI  - Culture Studies on Sphaerocarpos. III. The Utilization of Nitrogen by
      Sphaerocarpos texanus.

PMID- 16654814
TI  - Reduction of Ferricyanide by Algal Suspensions.

PMID- 16654815
TI  - Simple Large Scale Ultrafiltration Using Osmotically Forced Dialysis.

PMID- 16654816
TI  - The Promotion of Abscission by Auxin.

PMID- 16654817
TI  - Carbon Dioxide Fixation by Etiolated Plants after Exposure to White Light.

PMID- 16654818
TI  - Phosphorus and Sulfur Compounds in Plant Xylem Sap.

PMID- 16654819
TI  - Transient Changes in Cellular Gas Exchange and the Problem of Maximum Efficiency
      of Photosynthesis.

PMID- 16654820
TI  - Passive Permeation and Active Transport of Ions in Plant Roots.

PMID- 16654821
TI  - The Action of Benzimidazole on Lemna Minor.

PMID- 16654822
TI  - Changes in Catalase Activity and Other Responses Induced in Plants by Red and
      Blue Light.

PMID- 16654823
TI  - Effectiveness of Ethylene Diamine Tetra-Acetic Acid in the Activation of
      Oxidations Mediated by Mitochodria from Broccoli Buds.

PMID- 16654825
TI  - Hydrostatic Pressure in Coconuts.

PMID- 16654824
TI  - Infra-Red Absorption Spectra of Chlorophylls and Derivatives.

PMID- 16654826
TI  - Effect of Aqueous Perchloric Acid on the Xylan Content of Holocellulose from
      Cornstalks.

PMID- 16654827
TI  - Free Ribonucleic Acid Particles in Homogenates of Plant Tissue.

PMID- 16654828
TI  - The Role of Boron in the Translocation of Organic Compounds in Plants.

PMID- 16654829
TI  - Necessity of Indoleacetic Acid for the Duplication of Crown-Gall Tumor Cells.

PMID- 16654830
TI  - Effect of Manganese and Certain Other Metal Cations on Isocitric Dehydrogenase
      and Malic Enzyme Activities in Phaseolus vulgaris.

PMID- 16654831
TI  - The Absorption and Translocation of Sulfur in Red Kidney Bean.

PMID- 16654832
TI  - Studies in Plant Metabolism. VI. Effect of 2,4-D on the Metabolism of Aspartic
      Acid and Glutamic Acid in the Bean Plant.

PMID- 16654833
TI  - Particulate Adenylic Kinase in Higher Plants.

PMID- 16654834
TI  - Auxin-Induced Water Uptake by Avena Coleoptile Sections.

PMID- 16654835
TI  - Effects of Petroleum Oils on the Carbon Dioxide Output in Respiration of Parsnip
      and Mustard.

PMID- 16654836
TI  - Permeability of Avena Coleoptile Sections to Water Measured by Diffusion of
      Deuterium Hydroxide.

PMID- 16654837
TI  - A Statistical Evaluation of Some of the Factors Responsible for the Flow of Sap
      from the Sugar Maple.

PMID- 16654838
TI  - The Salt Respiration and Phosphate Contents of Barley Roots.

PMID- 16654839
TI  - Quantitative Determination of Buckwheat Flavonoid Substances by Direct
      Absorptiometry of Paper Chromatograms.

PMID- 16654840
TI  - Quantitative Changes in Buckwheat Flavonoid Substances During Seedling
      Development.

PMID- 16654841
TI  - Vitamin C Concentration in Developing and Mature Fruits of Mango (Mangifera
      indica L.).

PMID- 16654842
TI  - Effect of Maleic Hydrazide on Pineapple.

PMID- 16654844
TI  - Pathways of Oxidation in Cell-Free Potato Fractions.

PMID- 16654845
TI  - The Effect of 2,4-Dichlorophenoxyacetic Acid and 2,3,5-Triiodobenzoic Acid on the
      Transport of Indoleacetic Acid.

PMID- 16654846
TI  - Water Absorption by Needles of Ponderosa Pine Seedlings and Its Internal
      Redistribution.

PMID- 16654847
TI  - Metabolic Aspects of Neurospora Activation and Germination.

PMID- 16654848
TI  - Dehydrogenase Activity of Hydroxymalonate and Related Acids in Higher Plants.

PMID- 16654849
TI  - The Reactions of the Photoinductive Dark Period.

PMID- 16654850
TI  - Induction of Flowering in Long Day Plants by Applied Indoleacetic Acid.

PMID- 16654851
TI  - Effect of Bicarbonate Ion on the Respiration of Excised Roots.

PMID- 16654852
TI  - Absorption of Ionic Species of Orthophosphate by Barley Roots: Effects of 2,4
      Dinitrophenol and Oxygen Tension.

PMID- 16654853
TI  - Further Studies of Some Plant Indoles and Auxins by Paper Chromatography.

PMID- 16654855
TI  - Effects of Light on the Rate of Respiration in the Stem of Pisum Sativum L.

PMID- 16654854
TI  - An Auxin Inactivation System Involving Tyrosinase.

PMID- 16654857
TI  - Effects of Boron on the Water Relations of Higher Plants.

PMID- 16654858
TI  - Studies on the Growth of Coleoptile and First Internode Sections. A New,
      Sensitive, Straight-Growth Test for Auxins.

PMID- 16654859
TI  - Chlorine, Bromine and Sodium As Nutrients for Sugar Beet Plants.

PMID- 16654860
TI  - The Large Scale Laboratory Culture of Chlorella Under Conditions of Micronutrient
      Element Deficiency.

PMID- 16654861
TI  - Floral Initiation in Cestrum Nocturnum. I. A Long-Short Day Plant.

PMID- 16654862
TI  - The Conversion of CO(2) and CH(3)-CO-COOH to Citric and Malic Acids in the Tomato
      Fruits.

PMID- 16654863
TI  - Relation of Phosphorus Nutrition to the Translocation of 2,4
      Dichlorophenoxyacetic Acid in Tomato Plants.

PMID- 16654864
TI  - The Relation between Iron and Chlorophyll Contents in Chlorotic Sunflower Leaves.

PMID- 16654865
TI  - The Reduction and Oxidation of Glutathione by Plant Mitochondria.

PMID- 16654866
TI  - Pineapple Chlorosis in Relation to Iron and Nitrogen.

PMID- 16654867
TI  - Kinetics of Sulfate Absorption by Barley Roots.

PMID- 16654868
TI  - Plastid Pigment Changes in the Early Seedling Leaves of Zea Mays L.

PMID- 16654869
TI  - Studies on 3-Indoleacetic Acid Metabolism. II. Some Products of the Metabolism of
      Exogenous Indoleacetic Acid in Plant Tissues.

PMID- 16654870
TI  - Studies on 3-Indoleacetic Acid Metabolism. III. The Uptake of 3-Indoleacetic Acid
      by Pea Epicotyls and Its Conversion to 3-Indoleacetylaspartic Acid.

PMID- 16654871
TI  - Wax Deposits on Leaf Surfaces.

PMID- 16654872
TI  - The Physical Nature of Transpirational Pull.

PMID- 16654873
TI  - Effect of Ribonuclease on Salt Absorption by Excised Mung Bean Roots.

PMID- 16654874
TI  - Kinetin and Auxin Activity.

PMID- 16654875
TI  - Anesthetization by Di-Ethyl Ether and the Transport of Foliar Applied
      Radiocalcium.

PMID- 16654876
TI  - Effect of Spray Residues and Other Contaminants on Leaf Analysis.

PMID- 16654878
TI  - Oxidative Activity of Subcell Particles from a Number of Plant Species.

PMID- 16654879
TI  - Effects of a Series of Cycles of Alternating Low and High Soil Water Contents on
      the Rate of Apparent Photosynthesis in Sugar Cane.

PMID- 16654880
TI  - The Influence of Temperature on the Respiration of Cotton Leaf-Discs.

PMID- 16654882
TI  - Exogenous Substrate Utilization and Fermentation by the Pollen of Pinus
      ponderosa.

PMID- 16654881
TI  - Photoreversibility of Flower Initiation.

PMID- 16654883
TI  - Response of the Hypocotyl Hook of Bean Seedlings to Radiant Energy and Other
      Factors.

PMID- 16654884
TI  - Some Factors Affecting Absorption and Translocation of Zinc in Citrus Plants.

PMID- 16654885
TI  - The Metabolism of Glucose by the Alga Ochromonas malhamensis.

PMID- 16654886
TI  - Fat Metabolism in Higher Plants. VII. beta-Oxidation of Fatty Acids by Peanut
      Mitochondria.

PMID- 16654887
TI  - Respiration of Cucumber Fruits Associated with Physiological Injury at Chilling
      Temperatures.

PMID- 16654889
TI  - Absorption of Cobalt by Leaves of Bean Plants in the Dark.

PMID- 16654888
TI  - Effect of 2,4-Dichlorophenoxyacetic Acid and Other Growth-Regulators on the
      Formation of a Red Pigment in Jerusalem Artichoke Tuber Tissue.

PMID- 16654890
TI  - Similarity of Some Kinetin and Red Light Effects.

PMID- 16654891
TI  - Alfalfa Lipoxidase.

PMID- 16654892
TI  - Promotion of Leaf Expansion by Kinetin and Benzylaminopurine.

PMID- 16654893
TI  - Influence of Light and Darkness upon Carbon Dioxide Fixation.

PMID- 16654894
TI  - Atmospheric Fluoride: Its Uptake and Distribution in Tomato and Corn Plants.

PMID- 16654895
TI  - The Biosynthesis of Indoleacetic Acid in the Styles and Ovaries of Tobacco
      Preliminary to the Setting of Fruit.

PMID- 16654896
TI  - Intermediates of the Pentose Phosphate Pathway as Respiratory Substrates.

PMID- 16654897
TI  - Light Effects on the Germination of Seeds of Henbit (Lamium amplexicaule L.).

PMID- 16654898
TI  - The Residual Effect of Auxin on the Cell Wall.

PMID- 16654899
TI  - Experiments on the Biogenesis of the Pyridine Ring in Higher Plants.

PMID- 16654900
TI  - The Influence of Salts on the Activity of Particulate Cytochrome Oxidase from
      Roots of Higher Plants.

PMID- 16654901
TI  - Overwintering Trends of Cold Resistance and Carbohydrates in Medium Red, Ladino,
      and Common White Clover.

PMID- 16654902
TI  - Fluorescence-Spectrum Curves of Chlorophylls, Pheophytins, Phycoerythrins,
      Phycocyanins and Hypericin.

PMID- 16654903
TI  - Utilization of Betaine as a Methyl Group Donor in Tobacco.

PMID- 16654904
TI  - Effect of Micronutrient Deficiencies on Nicotine Formation by Tobacco in Water
      Culture.

PMID- 16654905
TI  - The Fate of 2,4-Dichlorophenoxyacetic Acid in Bean Seedlings. I. Recovery of 2,4
      Dichlorophenoxyacetic Acid and Its Breakdown in the Plant.

PMID- 16654906
TI  - The Intracellular Location of Phosphorylase in Tobacco (Nicotiana Tabacum L.).

PMID- 16654907
TI  - Some Studies of the Adsorption of Zinc Sulfate in Thompson Seedless Grape Canes.

PMID- 16654908
TI  - Vernalization in Peas.

PMID- 16654909
TI  - Effect of Sulfhydryl Inhibitors on Rubidium Absorption by Excised Mung Bean
      Roots.

PMID- 16654911
TI  - Some Phenotypic Effects of Single Gene Mutations on Respiratory Characteristics
      of Maize Leaf Tissue.

PMID- 16654910
TI  - Identification of Phosphoryl Choline as an Important Constituent of Plant Sap.

PMID- 16654912
TI  - Asymmetric Distribution of C in the Glucose Phosphates Formed During
      Photosynthesis.

PMID- 16654914
TI  - The Control of Plastid Pigment Formation by a Virescent Gene, Pale-Yellow-1, of
      maize.

PMID- 16654915
TI  - Oxidative Phosphorylation by Sweet Potato Mitochondria and Its Inhibition by
      Polyphenols.

PMID- 16654916
TI  - Cofactor Requirements for Oxidation of Alpha-Keto Acids by Sweet Potato
      Mitochondria.

PMID- 16654917
TI  - Floral Initiation in Cestrum nocturnum, A Long-Short Day Plant. II. A 24-Hour
      Versus a 16-Hour Photoperiod for Long Day Induction.

PMID- 16654918
TI  - Floral Initiation in Cestrum nocturnum, a Long-Short Day Plant. III. The Effect
      of Temperature upon Long Day and Short Day Induction.

PMID- 16654919
TI  - Studies on Tobacco Alkaloids. I. Changes in Nicotine and Nornicotine Content in
      Nicotiana.

PMID- 16654920
TI  - Utilization of Glycerol in the Tissues of the Castor Bean Seedling.

PMID- 16654921
TI  - The Fate of 2,4-Dichlorophenoxyacetic Acid in Bean Seedlings. II. Translocation.

PMID- 16654922
TI  - Indoleacetic Acid and the Utilization of Radioactive Pyruvate and Acetate by
      Wheat Roots.

PMID- 16654923
TI  - The Capacity of Leaves of Bryophyllum calycinum to Recover from Prolonged
      Exposure to Darkness or to Light.

PMID- 16654924
TI  - The Dark Fixation of CO(2) by Succulent Leaves: The First Products.

PMID- 16654925
TI  - Permeability of Vicia Faba Root Segments to Water as Measured by Diffusion of
      Deuterium Hydroxide.

PMID- 16654926
TI  - Effect of Radiation and Growth Regulators on Leaf Abscission in Seedling Cotton
      and Bean.

PMID- 16654927
TI  - Chlorophyllase in Soybean.

PMID- 16654928
TI  - A Simple Automatic Short Photoperiod Device.

PMID- 16654929
TI  - Photoperiodic Induction of Disbudded Perilla Plants.

PMID- 16654930
TI  - On the Significance of Measurements of Amino Acid Incorporation into the Proteins
      of Cell-free Preparations.

PMID- 16654931
TI  - Use of an Optical Planimeter for Measuring Leaf Area.

PMID- 16654933
TI  - The Rise of Sap in a Tropical Liana.

PMID- 16654934
TI  - Studies on the Growth of Citrus Seedlings with Different Forms of Nitrogen in
      Solution Cultures.

PMID- 16654935
TI  - Growth Repression of Higher Plants by 2-Pyridinethiol, 1-Oxide.

PMID- 16654936
TI  - Effect of Chemical Structure on the Growth Inhibition of Plants with Some Acid
      Analogs of 2-Mercaptobenzimidazole.

PMID- 16654937
TI  - Some Effect of Ascorbic Acid and Metal-Complexing Agents on the Respiration of
      Barley Roots.

PMID- 16654938
TI  - The Indole-3-Acetic Acid Oxidase of Lupinus albus L.

PMID- 16654939
TI  - Some Effects of Gibberellin on Flowering and Fruit Setting.

PMID- 16654940
TI  - Effects of Herbicides and Related Chemicals on Oxidation and Phosphorylation by
      Isolated Soybean Mitochondria.

PMID- 16654941
TI  - The Hexose Monophosphate Shunt as the Major Respiratory Pathway During
      Sporulation of Rust of Safflower.

PMID- 16654942
TI  - Moisture Transfer between Plants through Intertwined Root Systems.

PMID- 16654943
TI  - Translocatable Plant Growth Inhibitors Produced by Penicillium Thomii and
      Arachniotus trisporus.

PMID- 16654944
TI  - The Effect of Biuret on Protein Synthesis in Plants.

PMID- 16654945
TI  - The Effect of Prolonged Shading on the Light Saturation Curves of Apparent
      Photosynthesis in Sun Plants.

PMID- 16654946
TI  - Cell Space and Apparent Free Space in the Red Alga, Porphyra Perforata.

PMID- 16654947
TI  - Plastid Pigments of Gametophytes and Sporophytes of Musci.

PMID- 16654949
TI  - Studies on the Photosynthetic Reaction. III. The Effects of Various Inhibitors
      upon Growth and Carbonate-Fixation in Chlorella Pyrenoidosa.

PMID- 16654950
TI  - Metabolic Processes in Cytoplasmic Particles of the Avocado Fruit. III. The
      Operation of the Tricarboxylic Acid Cycle.

PMID- 16654951
TI  - Aspects of Phosphorus Metabolism in the Cotton Plant.

PMID- 16654952
TI  - Carbohydrate Distribution as Affected by Calcium Deficiency in Cotton.

PMID- 16654953
TI  - Effect of 6-(Substituted)Thio- and Amino-Purines on Germination of Lettuce Seed.

PMID- 16654954
TI  - Effects of Atmospheric Fluoride on the Respiration Rate of Bush Bean and
      Gladiolus Leaves.

PMID- 16654955
TI  - The Isolation of Nuclei and Oxidative Particles from Viable Wheat Embryos.

PMID- 16654956
TI  - Inductive Control of Indoleacetic Acid Oxidase Activity by Red and Near Infrared
      Light.

PMID- 16654957
TI  - The Effect of 2,4-Dichlorophenoxyacetic Acid on Pathways of Glucose Catabolism in
      Higher Plants.

PMID- 16654958
TI  - Comparative Absorption of Cobalt-60 by Upper and Lower Epidermis of Leaves.

PMID- 16654959
TI  - An Electronic Temperature Integrator for Plant Physiological Research.

PMID- 16654960
TI  - Studies of Maleic Hydrazide Interactions with Thiol Compounds.

PMID- 16654961
TI  - Foliar Symptoms of Deficiencies of Inorganic Elements in Tomato.

PMID- 16654962
TI  - Growth- and Enzyme-Inhibiting Properties of Bean Seed Extracts.

PMID- 16654964
TI  - A Paper Chromatographic Method for the Detection of 3-Amino-1,2,4-Triazole in
      Plant Tissues.

PMID- 16654963
TI  - Photosynthesis in Gibberellin-Treated Leaves.

PMID- 16654966
TI  - The Rest Period of Apricot Flower Buds as Described By a Regression of Time of
      Bloom on Temperature.

PMID- 16654967
TI  - Studies on Tobacco Alkaloids. II. The Formation of Nicotine and Nornicotine in
      Tobacco Supplied with N.

PMID- 16654968
TI  - Embryo Dormancy of Pinus jeffreyi Murr. Seed as Affected by Temperature, Water
      Uptake, Stratification, and Seed Coat.

PMID- 16654969
TI  - Analysis of Factors Determining Yield in Crop Plants. I. Varietal Differences in
      Yield of Grain and Straw of Wheat As Influenced by Photoperiodic Treatments.

PMID- 16654970
TI  - Analysis of Factors Determining Yield in Crop Plants. II. The Influence of
      Photoperiodic Treatments on Characters Determining Yield in Wheat with Special
      Reference to the Temperature of the Ripening Period.

PMID- 16654971
TI  - Mineral Nutrition of the Cotton Plant.

PMID- 16654972
TI  - A Re-examination of the Supposed Effect of Riboflavin on Growth.

PMID- 16654973
TI  - Participation of Cytochromes in the Respiration of the Aroid Spadix.

PMID- 16654974
TI  - Growth Stimulation of Avena Coleoptiles.

PMID- 16654975
TI  - The Dark Fixation of CO(2) by Succulent Leaves: Metabolic Changes Subsequent to
      Initial Fixation.

PMID- 16654976
TI  - The Products of CO(2) Fixation in Leaves of Long- and Short-Day Treated Kalanchoe
      blossfeldiana.

PMID- 16654977
TI  - Studies on the Organ of Production of the Natural Gibberellin Factor in Higher
      Plants.

PMID- 16654978
TI  - Mechanical Properties of the Avena Coleoptile As Related to Auxin and to Ionic
      Interactions.

PMID- 16654979
TI  - Effect of Galactose on Growth and Metabolism of Avena Coleoptile Sections.

PMID- 16654980
TI  - Methyl Esterification of Cell Wall Constituents under the Influence of Auxin.

PMID- 16654981
TI  - The Formation of Starch and the Behavior of Isocitric Acid in Excised Leaves of
      Bryophyllum calycinum Cultured in Darkness.

PMID- 16654982
TI  - Absorption and Translocation of 2,4-Dichlorophenoxyacetic Acid and P by Leaves.

PMID- 16654984
TI  - The Role of Cell Sap Concentration in Frost Hardiness.

PMID- 16654983
TI  - Growth in Vitro of Marigold and Tobacco Tissue with Nucleic Acids and Related
      Compounds.

PMID- 16654985
TI  - Altering the Pigments Produced by Tyrosinase and Ortho-Hydroxyphenols with a Meta
      Hydroxyphenol, 4-Chlororesorcinol.

PMID- 16654986
TI  - The Effect of 2,4-Dichlorophenoxyacetic Acid on the Accumulation of Mineral
      Elements in Tobacco Plants.

PMID- 16654989
TI  - Change of Editor-in-Chief.

PMID- 16654987
TI  - A Darkroom Safelight for Research in Plant Physiology.

PMID- 16654990
TI  - Studies of Carboxyl-C-Labeled 3-Indoleacetic Acid in Plants.

PMID- 16654991
TI  - Esterification of Phosphate in Ripening Fruit.

PMID- 16654992
TI  - Conversion of Tryptophan-2-C to Indoleacetic Acid by Watermelon Tissue Slices.

PMID- 16654993
TI  - Sedoheptulose in Coleus.

PMID- 16654994
TI  - Protein Synthesis During Water Uptake by Tuber Tissue.

PMID- 16654995
TI  - Molybdenum as a Plant Nutrient. X. Some Factors Affecting the Activity of Nitrate
      Reductase in Cauliflower Plants Grown with Different Nitrogen Sources and
      Molybdenum Levels in Sand Culture.

PMID- 16654996
TI  - Translocation of Organic Substances in Trees. I. The Nature of the Sugars in the
      Sieve Tube Exudate of Trees.

PMID- 16654997
TI  - Respiration of the Mycelia and Mitochondria of the Filamentous Watermold,
      Allomyces Macrogynus.

PMID- 16654998
TI  - Kinetics of Growth Inhibition by Herbicides.

PMID- 16654999
TI  - The Substitution of Complexing Substances for Boron in Plant Growth.

PMID- 16655001
TI  - Sodium and Silicon as Nutrients for the Tomato Plant.

PMID- 16655000
TI  - The Effect of Calcium on Potassium Accumulation in Corn and Soybean Roots.

PMID- 16655002
TI  - A Comparison of the Light Dependent Metabolism of Carbon Monoxide by Barley
      Leaves with that of Formaldehyde, Formate and Carbon Dioxide.

PMID- 16655003
TI  - Studies on the Formation of Ascorbic Acid in Detached Apple Leaves.

PMID- 16655004
TI  - Studies on the Physiology of Tomato Fruits. II. Ethylene Production at 20 degrees
      C as Related to Respiration, Ripening, and Date of Harvest.

PMID- 16655005
TI  - Changes in the Inositol Content During Germination and Growth of Some Higher
      Plants.

PMID- 16655006
TI  - Tartaric Acid Dehydrogenase Activity in Higher Plants.

PMID- 16655007
TI  - The Influence of Salts on Pyruvate Kinase from Tissues of Higher Plants.

PMID- 16655008
TI  - An Interference-Filter Monochromator System for the Irradiation of Biological
      Material.

PMID- 16655009
TI  - The Relation of Optical Form to the Utilization of Amino Acids. I. Utilization of
      Stereoisomeric Forms of Glutamic Acid by Carrot Root Disks.

PMID- 16655010
TI  - The Influence of Boron on Starch Phosphorylase and its Significance in
      Translocation of Sugars in Plants.

PMID- 16655011
TI  - The Effect of Gibberellic Acid on Enzyme Activity and Oxygen Uptake in Bean
      Plants (Phaseolus Vulgaris).

PMID- 16655012
TI  - A Spectrophotometric Assay of the Hill Reaction with Ferricyanide.

PMID- 16655013
TI  - Oxidative Phosphorylation by Subcellular Particles from Cabbage.

PMID- 16655015
TI  - The European Corn Borer, Pyrausta Nubilalis (Hubn), and Its Principal Host Plant.
      V. A Chemical Study of Host Plant Resistance.

PMID- 16655016
TI  - Properties of a Volatile Fraction from Uredospores of Puccinia graminis var.
      tritici Affecting Their Germination and Development. I. Biological Activity.

PMID- 16655017
TI  - Properties of a Volatile Fraction from Uredospores of Puccinia graminis var.
      tritici Affecting Their Germinaton and Development. II. Some Physical and
      Chemical Properties.

PMID- 16655018
TI  - Photocontrol of Anthocyanin Formation in Turnip and Red Cabbage Seedlings.

PMID- 16655019
TI  - Translocation of Organic Substances in Trees. II. On the Translocation Mechanism
      in the Phloem of White Ash (Fraxinus Americana L.).

PMID- 16655020
TI  - The Effect of Silicon on Yield and Manganese-54 Uptake and Distribution in the
      Leaves of Barley Plants Grown in Culture Solutions.

PMID- 16655021
TI  - Krebs Cycle Activity of Mitochondria from Endosperm of Sugar Pine Seed (Pinus
      Lambertiana Dougl.).

PMID- 16655022
TI  - Enzyme Activity of Mitochondria from Germinating Seedlings of Sugar Pine (Pinus
      Lambertiana Dougl.).

PMID- 16655023
TI  - Respiration and the Oxidative Activity of Particulate Fractions from Developing
      Pepper Fruits (Capsicum Annuum L.).

PMID- 16655024
TI  - Hydrogen Transport and Oxidative Phosphorylation by Particulates from Developing
      Pepper Fruits.

PMID- 16655025
TI  - Absorption and Mobility of Foliar Applied Nutrients.

PMID- 16655026
TI  - The Hill Reaction of Red Kidney Bean Chloroplasts.

PMID- 16655027
TI  - Effect of Gibberellin on Growth, Flowering and Fruiting of the Earlypak Tomato,
      Lycopersicum Esculentum.

PMID- 16655028
TI  - Growth of the Potato Tuber.

PMID- 16655029
TI  - Action Spectra of Photomorphogenic Induction and Its Photoinactivation.

PMID- 16655030
TI  - Factors Affecting Absorption and Translocation of Foliar Applied Phosphorus.

PMID- 16655031
TI  - The Presence of Ornithine Cycle Amino Acids in Some Higher Plants.

PMID- 16655033
TI  - Nicotine Production and Growth of Excised Tobacco Root Cultures.

PMID- 16655032
TI  - A Particulate Pyridine Nucleotide Oxidase System of the Wheat Embryo.

PMID- 16655034
TI  - Nicotine Production and Growth of Tobacco Scions on Tomato Rootstocks.

PMID- 16655036
TI  - Effects of Gibberellic Acid on the Photoperiod-Controlled Growth of Woody plants.

PMID- 16655035
TI  - Comments on the Absorption of Inorganic Ions by Root Cells.

PMID- 16655037
TI  - The Relationship of Temperature and Nutrition to the Growth of Sunflower Tumor
      Tissue in Vitro.

PMID- 16655038
TI  - The Kinetics of Potassium Accumulation by Corn Roots as a Function of Cell
      Maturity.

PMID- 16655039
TI  - Oxidation of Malonate by Peanut Mitochondria.

PMID- 16655040
TI  - Effect of Some Isomeric Purine Analogues on Germination of Lettuce Seed.

PMID- 16655041
TI  - The Role of pH in the Permeability of Chlorella to 2,4-D.

PMID- 16655042
TI  - On the Uptake of Carbon Dioxide and Bicarbonate by Roots, and Its Influence on
      Growth.

PMID- 16655043
TI  - Sulfhydryls in Plants. I. Reactions with Growth Regulators.

PMID- 16655044
TI  - Sulfhydryls in Plants. II. Distribution in Tissues.

PMID- 16655045
TI  - The Effect of 2,4-Dichlorophenoxyacetic Acid on the Respiration of Etiolated Pea
      Seedlings.

PMID- 16655046
TI  - Effects of Oxygen and Red Light upon the Absorption of Visible Light in Green
      Plants.

PMID- 16655047
TI  - Oxygen and Light Induced Oxidations of Cytochrome, Flavoprotein, and Pyridine
      Nucleotide in a Chlamydomonas Mutant.

PMID- 16655048
TI  - Malonyltryptophan in Higher Plants.

PMID- 16655049
TI  - Studies on 3-Indoleacetic Acid Metabolism. IV. Conjugation with Aspartic Acid and
      Ammonia as Processes in the Metabolism of Carboxylic Acids.

PMID- 16655050
TI  - Movement of C-Tagged Alpha-Methoxyphenylacetic Acid out of Roots.

PMID- 16655051
TI  - The Standardization of Poa Annua as an Indicator of Smog Concentrations. I.
      Effects of Temperature, Photoperiod, and Light Intensity during Growth of the
      Test-Plants.

PMID- 16655052
TI  - Physiology of the Cell Surface of Neurospora Ascospores. IV. The Functions of
      Surface Binding Sites.

PMID- 16655053
TI  - Carbon Dioxide Fixation into Oxalacetate in Higher Plants.

PMID- 16655054
TI  - Growth Regulators and Flowering. I. Survey Methods.

PMID- 16655055
TI  - An Analysis of Translocation in the Phloem of the Bean Plant Using Tho, P, And C.

PMID- 16655056
TI  - Electron Transport and Cytochromes of Sub-Cellular Particles from Cauliflower
      Buds.

PMID- 16655057
TI  - Factors Influencing Abscission.

PMID- 16655058
TI  - Growth Responses of Crucifers to Indoleacetic Acid and Indoleacetonitrile.

PMID- 16655059
TI  - The Relation of Optical Form to the Utilization of Amino Acids. II. Utilization
      of Stereoisomeric Varieties of Aspartic Acid and Asparagine by Carrot Root Disks.

PMID- 16655060
TI  - Rubber Biosynthesis in Latex of Hevea brasiliensis.

PMID- 16655061
TI  - Relationship of Boron Nutrition to Radiosensitivity of Sunflower Plants.

PMID- 16655062
TI  - The Effect of pH and Temperature on the Absorption Of Potassium and Bromide by
      Barley Roots.

PMID- 16655063
TI  - Metabolic Processes in Cytoplasmic Particles of the Avocado Fruit. IV. Ripening
      and the Supernatant Fraction.

PMID- 16655064
TI  - Biochemical Changes during Germination of the Tung Seed.

PMID- 16655066
TI  - Editor's Page.

PMID- 16655065
TI  - Catalase and Chlorophyll Depression by 3-Amino-1,2,4-Triazole.

PMID- 16655067
TI  - PLANT PHYSIOLOGISTS IN INDUSTRY: A Report Of The Committee On Professional Status
      And Training Of The American Society Of Plant Physiologists.

PMID- 16655068
TI  - Movement of Chlorine within Plants.

PMID- 16655069
TI  - Anthocyanins in Bracts of Euphorbia Pulcherrima as Revealed by Paper
      Chromatographic and Spectrophotometric Methods.

PMID- 16655070
TI  - Curvatures and Malformations in Bean Plants Caused by Culture Filtrate of
      Aspergillus niger.

PMID- 16655071
TI  - Intracellular Localization of the Tryptophan-indoleacetate Enzyme System.

PMID- 16655072
TI  - Oxidative Phosphorylation and Functional Cytochromes in Skunk Cabbage
      Mitochondria.

PMID- 16655073
TI  - Translocation of Sugars in the Concord Grape.

PMID- 16655074
TI  - Carbohydrate and Organic Acid Metabolism with C Distribution Affected by Copper
      in Thatcher Wheat.

PMID- 16655075
TI  - Beta-Alanine Protection of Yeast Growth Against the Inhibitory Action of Several
      Chlorinated Aliphatic Acid Herbicides.

PMID- 16655076
TI  - A Paper Chromatographic Separation of Gibberellic Acid and Gibberellin A.

PMID- 16655077
TI  - Growth of Etiolated Sections of Pea Internode Following Exposures to Indole-3
      Acetic Acid, 2,4-Dichlorophenoxyacetic Acid and 2,5-Dichlorobenzoic Acid.

PMID- 16655079
TI  - Carbohydrate Content of the Root Tip Cells of Allium Cepa.

PMID- 16655078
TI  - The Relation of the Cotyledons to Root Development of Pine Embryos Grown in
      Vitro.

PMID- 16655080
TI  - Malate Synthesis in Crassulacean Leaves. I. The Distribution of C in Malate of
      Leaves Exposed to CO(2) in the Dark.

PMID- 16655081
TI  - Effect of Triiodobenzoic Acid and Maleic Hydrazide upon the Transport of Foliar
      Applied Calcium and Iron.

PMID- 16655082
TI  - The Action Spectrum for Photosynthetic Phosphorylation by Spinach Chloroplasts.

PMID- 16655084
TI  - Pathways of Oxidation in Cell-free Potato Fractions. II. Properties of the
      Soluble Pyridine Nucleotide Oxidase System.

PMID- 16655085
TI  - An Effect of Gibberellic Acid on the Flowering of Xanthium, a Short Day Plant.

PMID- 16655086
TI  - The Assimilation of N-from Labeled Hyponitrite by Soybean Leaves.

PMID- 16655087
TI  - The Effects of Light Intensity on the Growth Rates of Green Algae.

PMID- 16655088
TI  - The Oxygen Affinity of a Flavin Oxidase Involved in the Respiration of
      Streptococcus faecalis.

PMID- 16655089
TI  - The Relationship of the Kinetin and Red-Light Promotions of Lettuce Seed
      Germination.

PMID- 16655090
TI  - Translocation of Photosynthetic Products to Soybean Nodules and Their Role in
      Nitrogen Fixation.

PMID- 16655091
TI  - The Properties of Cytochrome Oxidase in Cholate Extracts from Soybean Roots.

PMID- 16655092
TI  - Systemic Induction of Sprouting in White Potatoes by Foliar Applications of
      Gibberellin.

PMID- 16655093
TI  - Effects of Chloride and Sulfate Ions on the Growth, Leaf Burn, Composition and
      Anatomical Structure of Tobacco (Nicotiana Tabacum L.).

PMID- 16655094
TI  - Multiple Site Uptake of Individual Cations by Roots as Affected by Hydrogen Ion.

PMID- 16655095
TI  - Growth Substances in Corn Pollen.

PMID- 16655096
TI  - Utilization of D-Glucuronate by Corn Coleoptiles.

PMID- 16655097
TI  - Changes in Oxidative Enzyme Activity During the Curing of Connecticut Shade
      Tobacco.

PMID- 16655098
TI  - Observations on the Incorporation of C into Tartaric Acid and the Labeling
      Pattern of D-Glucose from an Excised Grape Leaf Administered L-Ascorbic Acid-6-C.

PMID- 16655100
TI  - Some Simplified Mathematical Treatments of Translocation in Plants.

PMID- 16655101
TI  - Effects of Indoleacetic Acid on the Utilization of Acetate-1-C by Pea Stem
      Slices.

PMID- 16655102
TI  - The Relationship of Magnesium Ion and Molecular Structure to 2,4
      Dichlorophenoxyacetic Acid and Some Related Compounds to the Inhibition of the
      Respiration of Azotobacter vinelandii.

PMID- 16655103
TI  - Direct Incorporation of Molecular Oxygen into Organic Material by Respiring Corn
      Seedlings.

PMID- 16655104
TI  - A Statistical Evaluation of a Growth Substance Bioassay Method Using Extracts of
      Dormant Peach Buds.

PMID- 16655105
TI  - Effect of Metal Chelates on Growth of Corn in Solution Cultures.

PMID- 16655106
TI  - The Water Content of Maple Stems. I. Application of the Karl Fischer Method for
      the Analyses of Water in Maple Bark and Wood.

PMID- 16655107
TI  - The Water Content of Maple Stems. II. Apparent Changes in the Water Content of
      Maple Stems and the Physiology of Maple Sap Flow.

PMID- 16655108
TI  - Effects of Some Essential Oil Vapors on the Stomata of Eupatorium and Mentha.

PMID- 16655109
TI  - Effects of Rosemary and Thyme Oil Vapors on the Stomata of Cherry Laurel.

PMID- 16655110
TI  - Photocontrol of Anthocyanin Synthesis in Apple Skin.

PMID- 16655111
TI  - Effect of 6-(Substituted) Purines and Gibberellin on the Rate of Seed
      Germination.

PMID- 16655112
TI  - The Fixation of CO(2) into Tartaric and Malic Acids of Excised Grape Leaves.

PMID- 16655113
TI  - Properties of Nolase in Extracts from Pea Seed.

PMID- 16655114
TI  - Enzymatic Formation of Indole-3-Carboxaldehyde from Indole-3-Acetic Acid.

PMID- 16655115
TI  - Translocation of Organic Substances in Trees. III. The Removal of Sugars from the
      Sieve Tubes in the White Ash (Fraxinus Americana L.).

PMID- 16655116
TI  - Fat Utilization and Composition in Germinating Cotton Seeds.

PMID- 16655117
TI  - Physiological Studies on Acid Metabolism in Green Plants. VI. Transaminases in
      Cell-Free Extracts from Kalanchoe Leaves.

PMID- 16655119
TI  - A New Method of Determining Drought Resistance.

PMID- 16655118
TI  - Studies on the Biosynthesis of Pectinic Acid Methyl Esters.

PMID- 16655121
TI  - Manganese Requirement with Respect to Growth, Hill Reaction and Photosynthesis.

PMID- 16655122
TI  - Light-dependent Oxygen Metabolism of Chloroplast Preparations. I. Stimulation
      Following Quinone Reduction.

PMID- 16655123
TI  - Quantitative Assay of Chlorogenic Acid and its Pattern of Distribution within
      Tobacco Leaves.

PMID- 16655124
TI  - Algal Growth in Crossed Gradients of Light Intensity and Temperature.

PMID- 16655125
TI  - Absence of Seed Dormancy in a White Mutant Strain of Helianthus annuus L.

PMID- 16655126
TI  - A Comparison of Chlorogenic Acid and Catechol as Substrates for the Polyphenol
      Oxidase from Tobacco and Mushroom.

PMID- 16655127
TI  - Endogenous Bud and Root Formation by Isolated Roots of Convolvulus Grown in
      Vitro.

PMID- 16655128
TI  - The Osmotic Cell, Solute Diffusibility, and the Plant Water Economy.

PMID- 16655129
TI  - Propagation of Turgor and Other Properties Through Cell Aggregations.

PMID- 16655130
TI  - Osmosis and Diffusion in Tissue: Half-times and Internal Gradients.

PMID- 16655131
TI  - Non-metabolic Uptake of Ions by Barley Roots.

PMID- 16655132
TI  - Chemical Constitution of the Primary Cell Walls of Avena Coleoptiles.

PMID- 16655133
TI  - Effect of Light on the Co(2) Absorption and Evolution by Kalanchoe, Wheat and Pea
      Leaves.

PMID- 16655134
TI  - Circulation Patterns for Phosphorus, Sulfur and Calcium in the Bean Plant.

PMID- 16655135
TI  - Relation of Potassium Nutrition to the Translocation of 2,4-Dichlorophenoxyacetic
      Acid in Tomato Plants.

PMID- 16655137
TI  - Biochemical Studies of Chilling Injury in Sweetpotatoes.

PMID- 16655138
TI  - Auxin Activity of Some Indole Derivatives.

PMID- 16655139
TI  - Depth Controlled Deuteron Irradiation of Lactuca sativa Seeds. I. Effects On
      Germination and Growth.

PMID- 16655140
TI  - Depth Controlled Deuteron Irradiation of Lactuca sativa Seeds. II. Energy Loss in
      the Outer Seed Layers.

PMID- 16655141
TI  - Gibberellic Acid, Part VI. The Biological Activity of alloGibberic Acid and Its
      Identity with Gibberellin B.

PMID- 16655142
TI  - Biosynthesis of Hordenine in Tissue Homogenates of Panicum miliaceum L.

PMID- 16655143
TI  - The Chemical Nature of Silica in Plants.

PMID- 16655144
TI  - Compositional Factors Associated with the Growth Responses of Young Cotton Plants
      to Gibberellic Acid.

PMID- 16655145
TI  - Effects of High Temperature on Yield of Peas.

PMID- 16655146
TI  - Ornithine, Citrulline, and Arginine Metabolism in Watermelon Seedlings.

PMID- 16655147
TI  - Triphosphopyridine Nucleotide Diaphorase from Wheat Germ.

PMID- 16655148
TI  - Action Spectrum of Phototropic Tip-Curvature of Avena.

PMID- 16655149
TI  - Effect of Bicarbonate on the Enzymic Synthesis of Long Chain Fatty Acids.

PMID- 16655150
TI  - Effect of Petroleum Ether Extraction and Readdition of Various Compounds on the
      Photochemical Activity of Isolated Chloroplasts.

PMID- 16655151
TI  - Effects of Temperature on Growth and Dry Matter Accumulation of Peas.

PMID- 16655152
TI  - Production, Translocation and Accumulation of Alkaloids in Tobacco Scions Grafted
      to Tomato Rootstocks.

PMID- 16655154
TI  - Measurement of Sap Flow in Conifers by Heat Transport.

PMID- 16655155
TI  - Identification and Estimation of Catabolic Pathways of Glucose in Fruits.

PMID- 16655156
TI  - Dark Fixation of CO(2) by Succulent Leaves: Conservation of the Dark Fixed CO(2)
      Under Diurnal Conditions.

PMID- 16655157
TI  - Respiration of Developing Rose Petals.

PMID- 16655158
TI  - Photocontrol of Alcohol, Aldehyde, and Anthocyanin Production in Apple Skin.

PMID- 16655159
TI  - Lipid Soluble Pigments of Wheat Plants as Related to Hessian Fly Infestation.

PMID- 16655160
TI  - Effect of Ozone and Ozonated 1-hexene on Respiration and Photosynthesis of
      Leaves.

PMID- 16655161
TI  - Iodine as a Micronutrient for Tomatoes.

PMID- 16655162
TI  - Distribution of Boron in Cells of Dicotyledonous Plants in Relation to Growth.

PMID- 16655163
TI  - On the Action of Plant Growth Regulators. II. Adsorption of MCPA to Plant
      Components.

PMID- 16655164
TI  - Free Amino Acid Levels in Nicotiana glauca, N. Langsdorffii and Their
      Interspecific Hybrid Following Gamma Irradiation.

PMID- 16655165
TI  - Correction to the Paper Entitled "Osmosis and Diffusion in Tissue: Half-times and
      Internal Gradients.".

PMID- 16655167
TI  - Stimulation of Lettuce Seed Germination by 6-(Substituted) Purines.

PMID- 16655169
TI  - An Analysis of Auxin-gibberellin Interaction in Pea Stem Tissue.

PMID- 16655168
TI  - Effects of Atmospheric Fluorides and Various Types of Injury on the Respiration
      of Leaf Tissue.

PMID- 16655170
TI  - Foliar Uptake of Salt Constituents of Water by Citrus Plants During Intermittent
      Sprinkling and Immersion.

PMID- 16655171
TI  - Metabolic Studies of Applied Indoleacetic Acid-1-C in Plant Tissues as Affected
      by Light and 2,4-D Treatment.

PMID- 16655172
TI  - Influence of 2,4-Dichlorophenoxyacetic Acid on Solute Uptake by Chlorella.

PMID- 16655173
TI  - The Electron Transfer System of Skunk Cabbage Mitochondria.

PMID- 16655174
TI  - The Response of The Young Tomato Plant to a Brief Period of Water Shortage. IV.
      Effects of Water Stress on the Ribonucleic Acid Metabolism of Tomato Leaves.

PMID- 16655175
TI  - Chloroplast Isolation in Nonaqueous Media.

PMID- 16655176
TI  - Effect of 2,3,6-Trichlorobenzoic Acid and 2,6-Dichlorobenzoic Acid on the
      Geotropic and Phototropic Responses of Seedlings of Various Species.

PMID- 16655177
TI  - Effects of Growth-regulating Substances on the Carbon Dioxide Evolution and Post
      harvest Ripening of Tomatoes.

PMID- 16655178
TI  - Studies on Sulfate Utilization by Chlorella pyrenoidosa using Sulfate-S; the
      Occurrence of S-Adenosyl Methionine.

PMID- 16655179
TI  - Electron Transport Mechanisms in Tobacco Roots. I. Studies on the Cytochrome and
      Related Systems.

PMID- 16655181
TI  - Comparative Responses of Carbon Dioxide Outburst and Uptake in Tobacco.

PMID- 16655182
TI  - Some Effects of Temperature and Carbon Dioxide Concentration on Photosynthesis of
      Mimulus.

PMID- 16655183
TI  - Effect of Acid Scarification on Lupine Seed Impermeability.

PMID- 16655184
TI  - Some Factors which Affect the Synthesis of Chlorogenic Acid in Disks of Potato
      Tuber.

PMID- 16655185
TI  - Effect of 2,4-Dichlorophenoxyacetic Acid and 2,4-Dinitrophenol on the Uptake and
      Metabolism of Exogenous Substrates by Corn Roots.

PMID- 16655186
TI  - Effect of Some Substituted Benzoic Acids and Related Compounds on the
      Distribution of Callus Growth in Tobacco Stem Explants.

PMID- 16655187
TI  - Dark Fixation of CO(2) by Tobacco Leaves.

PMID- 16655188
TI  - Internal Distribution of Coenzyme Q in Higher Plants.

PMID- 16655190
TI  - Formation of beta-Phenylglucoside in Plant Leaves.

PMID- 16655189
TI  - Studies of the Rest Period. I. Growth, Translocation, and Respiratory Changes in
      the Embryonic Organs of the After-ripening Cherry Seed.

PMID- 16655191
TI  - Oxidation of Indoleacetic Acid by Quackgrass Rhizomes.

PMID- 16655192
TI  - Malonate as a Participant in Organic Acid Metabolism in Bush Bean Leaves.

PMID- 16655193
TI  - Enzymatic Degradation of Adenosine Triphosphate to Adenine by Cabbage Leaf
      Preparations.

PMID- 16655194
TI  - Growth and Development of Isolated Phycomyces Sporangiophores.

PMID- 16655195
TI  - Gibberellin in the Induction of Parthenocarpy in Zephyranthes.

PMID- 16655196
TI  - Metabolism of Citrulline and Ornithine in Mung Bean Mitochondria.

PMID- 16655198
TI  - Effects of Petroleum Oils On the Oxygen Uptake in Respiration of Parsnip and
      Mustard.

PMID- 16655199
TI  - Light Induced Absorption Changes in Photosynthetic Organisms. II. A Split-beam
      Difference Spectrophotometer.

PMID- 16655200
TI  - Influence of Selective Light Scattering on Measurements of Absorption Spectra of
      Chlorella.

PMID- 16655201
TI  - Chromatic Transients in the Photosynthesis of a Green Alga.

PMID- 16655202
TI  - Induction of Fluorescence in Quinone Poisoned Chlorella Cells.

PMID- 16655203
TI  - Quantum Requirement for Phosphopyridine Nucleotide Reduction in Photosynthesis.

PMID- 16655204
TI  - Primary Photochemical and Photophysical Processes in Photosynthesis.

PMID- 16655205
TI  - Further Studies on the Carbon Dioxide Burst in Algae.

PMID- 16655206
TI  - Complexities of Manometric Measurement of Changing Rates of Gas Production.

PMID- 16655207
TI  - Relation Between Respiration and Photosynthesis in the Green Alga, Ankistrodesmus
      braunii.

PMID- 16655208
TI  - Kinetic Relationships Between Photosynthesis and Respiration in the Algal
      Flagellate, Ochromonas Malhamensis.

PMID- 16655210
TI  - Photoreduction of Chlorophyll a in the Presence of Ascorbic Acid in Pyridine
      Solutions.

PMID- 16655209
TI  - Pyocyanine and Phosphorylation with Chloroplasts.

PMID- 16655211
TI  - Photoreduction and Photooxidation of Cytochrome c by Spinach Chloroplast
      Preparations.

PMID- 16655212
TI  - Fractionation and Purification of Cytochrome C Photooxidase of Spinach.

PMID- 16655213
TI  - Comparison of Three Photochemical Activities of Chloroplasts.

PMID- 16655214
TI  - Uncouplers of Spinach Chloroplast Photosynthetic Phosphorylation.

PMID- 16655215
TI  - Comparison of Ferricyanide and 2,3',6-Trichlorophenol Indophenol as Hill Reaction
      Oxidants.

PMID- 16655216
TI  - Stability of Isolated Chloroplast Preparations and its Effect on Hill Reaction
      Measurements.

PMID- 16655217
TI  - A Pyridine Nucleotide-Cytochrome C Reductase Isolated from Chloroplasts.

PMID- 16655218
TI  - The Mechanism of the Photochemical Activity of Isolated Chloroplasts. III.
      Dependence of Velocity on Light Intensity.

PMID- 16655219
TI  - The Mechanism of the Photochemical Activity of Isolated Chloroplasts. V.
      Interpretation of the Rate Parameters.

PMID- 16655220
TI  - Absorption Spectra and Relative Photostability of the Different Forms of
      Chlorophyll in Chlorella.

PMID- 16655221
TI  - Reduction of Chlorophyllides, Chlorophylls and Chlorophyll Derivatives by Sodium
      Borohydride.

PMID- 16655222
TI  - Chloroplast Lipids as Carbohydrate Reservoirs.

PMID- 16655223
TI  - Factors Affecting Light Induced Fixation of Carbon Dioxide by Isolated Spinach
      Chloroplasts.

PMID- 16655224
TI  - Intracellular and Phylogenetic Distribution of Ribulose 1,5-Diphosphate
      Carboxylase and D-Glyceraldehyde-3-Phosphate Dehydrogenases.

PMID- 16655225
TI  - Biosynthesis and Possible Functional Relationships Among the Carotenoids; and
      Between Chlorophyll a and Chlorophyll b.

PMID- 16655226
TI  - Studies on Nitrogen Fixation and Photosynthesis of Rhodospirillum Rubrum.

PMID- 16655227
TI  - Pigment Carrying Structures of the Photosynthetic Non-sulphur Purple Bacterium
      Rhodopseudomonas Spheroides.

PMID- 16655228
TI  - Formation and Bleaching of Chlorophyll in Albino Corn Seedlings.

PMID- 16655229
TI  - On the Mass Culture of Algae. II. Yield as a Function of Cell Concentration Under
      Continuous Sunlight Irradiance.

PMID- 16655230
TI  - A Sensitive Stage in Synchronized Cultures of Chlorella.

PMID- 16655233
TI  - Robert Emerson, 1903-1959.

PMID- 16655231
TI  - Efficiency of Light Energy Conversion in Plant Growth.

PMID- 16655234
TI  - Studies on Auxin-membrane Permeability Relations in Fruit and Leaf Tissues.

PMID- 16655235
TI  - Some Metabolic Responses of Alfalfa Seedlings to Freezing.

PMID- 16655236
TI  - Metabolism of C-Bicarbonate, P-Phosphate, or S-Sulfate by Lettuce Seed during
      Germination.

PMID- 16655237
TI  - Mechanisms of action of Polymyxin B on Chlorella and Scenedesmus.

PMID- 16655238
TI  - On the Occurrence of Free-galacturonic Acid in Apples and Tomatoes.

PMID- 16655239
TI  - Enzyme Activation in Wheat Grains in Relation to Water Content. Glutamic Acid
      Alanine Transaminase, and Glutamic Acid Decarboxylase.

PMID- 16655240
TI  - Methods for the Extraction of Enzymes from Cereal Leaves with Especial Reference
      to the Triosephosphate Dehydrogenases.

PMID- 16655241
TI  - Effects of Artificial Increases in Sugar Content on Frost Hardiness.

PMID- 16655242
TI  - Distribution and Properties of Isocitritase in Plants.

PMID- 16655243
TI  - Changes in Endogenous Growth Substances during Flower Development.

PMID- 16655244
TI  - Inverse Effects of Gibberellin on Peroxidase Activity and Growth in Dwarf Strains
      of Peas and Corn.

PMID- 16655245
TI  - Effect of Light upon the Behaviour of Citric Acid in Leaves of Bryophyllum
      Calycinum Salisb.

PMID- 16655246
TI  - Respiratory and Associated Responses of Carrot Disc to Substituted Phenols.

PMID- 16655247
TI  - Studies on the Mechanism of Herbicidal Action of 2-Chloro-4,6-Bis(Ethylamino)-S
      Triazine.

PMID- 16655248
TI  - Comparison of the Nucleic Acid, Total Nitrogen, and Protein Nitrogen Levels of
      Normal and Tumor Tissue under Similar Growth Conditions.

PMID- 16655249
TI  - Physiology of Growth and Reproduction in Rice. II. Effect of Plant Growth
      Substances on Three Winter Varieties.

PMID- 16655250
TI  - Effects of Iron and Chelating Agents on Dark Carboxylation Reactions in Plant
      Homogenates.

PMID- 16655251
TI  - Loss of Phosphorus-32 by Plant Roots after Foliar Application.

PMID- 16655252
TI  - Germination of Light Sensitive Seed in Crossed Gradients of Temperature and
      Light.

PMID- 16655253
TI  - Studies on the Mechanism of Stem Growth Inhibition by Visible Radiation.

PMID- 16655254
TI  - Growth Responses of Alaska Pea Seedlings to Visible Radiation and Gibberellic
      Acid.

PMID- 16655255
TI  - Endogenous Substrates of Dormant, Activated and Germinating Ascospores of
      Neurospora Tetrasperma.

PMID- 16655256
TI  - Influence of Temperature on the Response of Germinating Barley Grains to
      Potassium Gibberellate.

PMID- 16655257
TI  - Phosphorus Compounds of Cotton Embryos and Their Changes during Germination.

PMID- 16655258
TI  - Winter Freezing in Relation to the Rise of Sap in Tall Trees.

PMID- 16655260
TI  - Tryptophan Synthetase Activity in Pea Seedling Extracts.

PMID- 16655261
TI  - Identification of the Anthocyanins in Petals of Tulip Varieties Smiling Queen and
      Pride of Haarlem.

PMID- 16655262
TI  - Formation of Embryo Starch During Germination as an Indicator of Viability and
      Vigor in Heat-Damaged Barley.

PMID- 16655263
TI  - Nitrogen and Sulfur Changes Associated with Growth Uncoupled from Cell Division
      in Chlorella vulgaris.

PMID- 16655264
TI  - Translocation of Calcium in the Bean Plant.

PMID- 16655265
TI  - Fixation of Carbon Dioxide in Particulate Preparations from Barley Roots.

PMID- 16655266
TI  - Carbon Dioxide Fixation and Salt Uptake in Particulate Preparations from Barley
      Roots.

PMID- 16655267
TI  - Effect of Tissue Age on Hexose Metabolism. I. An Enzyme Study with Pea Root.

PMID- 16655268
TI  - An Airflow Planimeter for Measuring the Area of Detached Leaves.

PMID- 16655269
TI  - Anthocyanin Synthesis in Corn Endosperm Tissue Cultures. I. Identity of the
      Pigments and General Factors.

PMID- 16655270
TI  - Amide Metabolism in Higher Plants. III. Distribution of Glutamyl Tranferase and
      Glutamine Synthetase Activity.

PMID- 16655271
TI  - Isolation of Two Quinones with Coenzyme Q Activity from Alfalfa.

PMID- 16655272
TI  - Kinetics and Properties of Cytochrome c Photooxidase of Spinach.

PMID- 16655273
TI  - Activation of Germination in Douglas Fir Seed by Hydrogen Peroxide.

PMID- 16655274
TI  - Alteration of the Protein Components and other Constituents in the Tobacco Leaf
      by Shading.

PMID- 16655275
TI  - Experimental Modification of Plant Senescence.

PMID- 16655276
TI  - Latitudinal Effect on Respiration in some Northern Plants.

PMID- 16655277
TI  - Factors in Corn Steep Water Promoting Growth of Plant Tissues.

PMID- 16655278
TI  - Use of Specifically Labeled Glucose and Gluconate in the Evaluation of Catabolic
      Pathways for Glucose in Corn Roots.

PMID- 16655279
TI  - An Inhibitor of Oxalic Acid Oxidase in Beet Extracts.

PMID- 16655281
TI  - A Soluble Pyridine Nucleotide Oxidase System from Barley Roots.

PMID- 16655282
TI  - Growth Regulators and Flowering. II. The Cobaltous Ion.

PMID- 16655283
TI  - Flowering in Fruit Trees and Annual Plants as Affected by Purines, Pyrimidines
      and Triiodobenzoic Acid.

PMID- 16655284
TI  - Molybdenum-Manganese-Iron Antagonisms in the Nutrition of Tomato Plants.

PMID- 16655285
TI  - Further Studies on Comparative Mobility of Labeled Herbicides.

PMID- 16655286
TI  - Some Observations on Potassium Accumulation in Corn Root Mitochondria.

PMID- 16655287
TI  - The Aseptic Culture of Isolated Buds of Pseudotsuga Taxifolia.

PMID- 16655288
TI  - An Improved Technique for the Growth of Chlorella in CO(2).

PMID- 16655289
TI  - The Effects of Triiodobenzoic Acid and Urea on the Response of Chlorotic Lemon
      (Citrus Limonia) Trees to Foliar Application of Iron Compounds.

PMID- 16655290
TI  - Effect of Vernalization on Heat Resistance in Two Varieties of Peas.

PMID- 16655291
TI  - The Possible Role of Adenosine Triphosphate in Rubidium Absorption as Revealed by
      the Influence of External Phosphate, Dinitrophenol and Arsenate.

PMID- 16655292
TI  - Ribulose 1,5-Diphosphate Carboxylase Activity in Relation to Photosynthesis by
      Intact Leaves And Isolated Chloroplasts.

PMID- 16655293
TI  - Estimated Contributions of Root and Shoot to the Nicotine Content of the Tobacco
      Plant.

PMID- 16655294
TI  - A Wide-Range A.C. Bridge for Determining Injury and Death.

PMID- 16655295
TI  - Nitrogen Mobilization in Pea Seedlings.

PMID- 16655296
TI  - Bound Water and Frost Hardiness.

PMID- 16655298
TI  - An Analysis of "Dark-osmotic Inhibition" of Germination of Lettuce Seeds.

PMID- 16655299
TI  - Malate Synthetase in Higher Plants.

PMID- 16655300
TI  - Differences Between Lignin-like Polymers Formed by Peroxidation of Eugenol and
      Ferulic Acid in Leaf Sections of Phleum.

PMID- 16655301
TI  - Ethionine Inhibition and Morphogenesis of Excised Tomato Roots.

PMID- 16655302
TI  - Influence of Extended Storage at Constant Low Temperature on Cold Resistance and
      Carbohydrate Reserves of Alfalfa and Medium Red Clover.

PMID- 16655303
TI  - Photocontrol of Formation of Red Kidney Bean Leaf Triphosphopyridine Nucleotide
      Linked Triosephosphate Dehydrogenase.

PMID- 16655304
TI  - Intracellular Mechanism of Growth Inhibition by Radiant Energy.

PMID- 16655305
TI  - Biological Activity of Tetrazole Analogues of Indole-3-Acetic Acid and 2,4
      Dichlorophenoxyacetic Acid.

PMID- 16655306
TI  - Some Relationships Between the Production of Carbon Dioxide by Roots and Lime
      Tolerance of Fruit Trees and Grape Vine Hybrids.

PMID- 16655308
TI  - Arginine-requiring Strains of Tissue Obtained from Ginkgo Pollen.

PMID- 16655309
TI  - Studies on the Ethylene Production of Apple Tissue.

PMID- 16655310
TI  - Stimulation of the Respiration of Chlorella Vulgaris by Purines and Purine
      Analogues.

PMID- 16655311
TI  - Metabolic Responses to Auxin. V. Dissociation by Carbon Monoxide of Effects of
      Indoleacetic Acid on Growth and Respiration.

PMID- 16655312
TI  - The Metabolism of Nitrate and Ammonia by Chlorella.

PMID- 16655313
TI  - Translocation III. Experiments with Carbon 14, Chlorine 36, and Hydrogen 3.

PMID- 16655314
TI  - Radioautography of Tritiated Photosynthate Arising from HTO.

PMID- 16655315
TI  - On the Nature of Glutamic Acid Decarboxylase in Wheat Embryos.

PMID- 16655316
TI  - Uptake and Metabolism of Sulfate by Chlorella. I. Sulfate Accumulation and Active
      Sulfate.

PMID- 16655317
TI  - Studies on Development of Cyanide-resistant Respiration in Potato Tuber Slices.

PMID- 16655318
TI  - Phosphorus Metabolism of Trifolium Hirtum All. As Affected by 2,4
      Dichlorophenoxyacetic Acid and Gibberellic Acid.

PMID- 16655319
TI  - Pectic Metabolism of Growing Cell Walls.

PMID- 16655320
TI  - Interactions of Gibberellin, Vernalization, Photoperiod and Temperature in the
      Flowering of Endive.

PMID- 16655321
TI  - Possible Role of Pectic Enzymes in Abscission.

PMID- 16655322
TI  - Effects of Indoleacetic Acid and Other Oxidation Regulators on in Vitro
      Peroxidation and Experimental Conversion of Eugenol to Lignin.

PMID- 16655323
TI  - Separation of Mechanisms Initiating Cell Division and Cell Expansion in Lettuce
      Seed Germination.

PMID- 16655324
TI  - Inhibition of Photoperiodic Induction by 5-Fluorouracil.

PMID- 16655325
TI  - Effect of 2,4-Dichlorophenoxyacetic acid Application on Activity and Composition
      of Mitochondria from Soybeans.

PMID- 16655326
TI  - Inhibitory Effect of Water on Oxygen Consumption by Plant Materials.

PMID- 16655327
TI  - Photosynthesis by Isolated Chloroplasts IX. Photosynthetic Phosphorylation and
      CO(2) Assimilation in Different Species.

PMID- 16655328
TI  - Action and Transmission Spectra of Phycomyces.

PMID- 16655329
TI  - Oxidative Phosphorylation and Glycolate Oxidation by Particles from Spinach
      Leaves.

PMID- 16655330
TI  - Effect of Growth on Redistribution of Some Mineral Elements in Peppermint.

PMID- 16655331
TI  - Studies on Lateral Movement of Phosphorus 32 in Peppermint.

PMID- 16655332
TI  - Studies on 3-Indoleacetic Acid Metabolism. V. Effect of Calcium Ions on 3
      indoleacetic Acid Uptake and Metabolism by Pea Roots.

PMID- 16655333
TI  - Studies on 3-Indoleacetic Acid Metabolism. VI. 3-Indoleacetic Acid Uptake and
      Metabolism by Pea Roots and Epicotyls.

PMID- 16655334
TI  - A Secondary Photosynthetic Carboxylation.

PMID- 16655335
TI  - Interaction of Endogenous and Environmental Periods in Plant Growth.

PMID- 16655336
TI  - Relationship of Growth and Development to Changes in Sugars, Auxins, and
      Gibberellins in Fruit of Seeded and Seedless Varieties of Vitis Vinifera.

PMID- 16655337
TI  - Influences of Gibberellic Acid on Metabolism of Indoleacetic Acid, Acetate, and
      Glucose in Roots of Higher Plants.

PMID- 16655338
TI  - Separation of Plant Growth Regulating Substances on Silica Gel Columns.

PMID- 16655339
TI  - Growth Promotion in Pea Stem Sections. I. Stimulation of Auxin and Gibberellin
      Action by Alkyl Lipids.

PMID- 16655340
TI  - Biosynthesis of Sucrose and Sucrose-Phosphate by Sugar Beet Leaf Extracts.

PMID- 16655341
TI  - Some Anatomical Effects of Kinetin and Red Light on Disks of Bean Leaves.

PMID- 16655342
TI  - Automatic Device for Controlling Lengths of Light and Dark Periods in Cycles of
      any Desired Duration.

PMID- 16655344
TI  - Net Assimilation Rate and Growth Behavior of Beans as Affected by Gibberellic
      Acid Urea and Sugar Sprays.

PMID- 16655345
TI  - Conditions Affecting Enzyme Synthesis in Cotyledons of Germinating Seeds.

PMID- 16655346
TI  - Physiological Effects of Gibberellic Acid: I. On Carbohydrate Metabolism and
      Amylase Activity of Barley Endosperm.

PMID- 16655347
TI  - Cohesion of Water in Plants.

PMID- 16655348
TI  - Light-Dependent Oxygen Metabolism of Chloroplast Preparations. II. Stimulation by
      Manganous Ions.

PMID- 16655349
TI  - Composition of Developing Primary Wall in Onion Root Tip Cells. I. Quantitative
      Analyses.

PMID- 16655350
TI  - Differential Uptake of 2,4-D Acid and Its Octyl Ester by Seedling Corn Roots and
      Coleoptile Sections.

PMID- 16655351
TI  - Products of Orthophosphate Absorption by Barley Roots.

PMID- 16655352
TI  - Promotion of Lettuce Seed Germination by Gibberellin.

PMID- 16655353
TI  - Transpirational Surges in Tamarix and Eucalyptus as Measured with an Infrared Gas
      Analyzer.

PMID- 16655354
TI  - Separation and Identification of Soluble Nucleotides from Etiolated Corn
      Seedlings as Function of Growth.

PMID- 16655355
TI  - Role of Calcium in Absorption of Monovalent Cations.

PMID- 16655356
TI  - Effect of Gibberellic Acid and Photoperiod on Indoleacetic Acid Oxidase in
      Lupinus Albus L.

PMID- 16655357
TI  - Differential Absorption of Metal Chelate Components by Plant Roots.

PMID- 16655358
TI  - Chlorophyllase Activity of Spinach Chloroplastin.

PMID- 16655359
TI  - Impairment of Respiration, Ion Accumulation, and Ion Retention in Root Tissue
      Treated with Ribonuclease and Ethylenediamine Tetraacetic Acid.

PMID- 16655360
TI  - (2-Chloroethyl) Trimethylammonium Chloride and Related Compounds as Plant Growth
      Substances. II. Effect on Growth of Wheat.

PMID- 16655361
TI  - Formate Oxidation by Particulate Preparations from Higher Plants.

PMID- 16655362
TI  - Evaluation of Light Sources for Plant Growth.

PMID- 16655363
TI  - Factors Affecting Growth of Tobacco Callus Tissue and Its Incorporation of
      Tyrosine.

PMID- 16655364
TI  - Influence of 2,4-Dichlorophenoxyacetic Acid on Pathways of Glucose Utilization in
      Bean Stem Tissues.

PMID- 16655365
TI  - Movement and Distribution of Radiophosphorus in Crowns of Healthy and Pole
      Blighted Western White Pines. (Pinus Monticola D. Don.).

PMID- 16655366
TI  - Uptake and Utilization of Phosphate Associated With Respiratory Changes in Potato
      Tuber Slices.

PMID- 16655367
TI  - Photosynthesis and Respiration in Developing Fruits. I. CO(2) Uptake by Young
      Oranges in Light and in Dark.

PMID- 16655368
TI  - Carbohydrate Metabolism of Citrus Fruits. I. Mechanisms of Sucrose Synthesis in
      Oranges and Lemons.

PMID- 16655369
TI  - Absorption, Distribution, and Destruction of Indoleacetic Acid in Plum Stem
      Cuttings.

PMID- 16655370
TI  - Effect of Water Stress on Cell Wall Metabolism of Avena Coleoptile Tissue.

PMID- 16655371
TI  - An Artifact in Chromatography of Indolic Auxins.

PMID- 16655372
TI  - Physiological Studies on Nodule-Nitrate Reductase.

PMID- 16655373
TI  - Isocitritase, Glycine-Alanine Transaminase, and Development in Blastocladiella
      Emersonii.

PMID- 16655374
TI  - Red Drop and Role of Auxiliary Pigments in Photosynthesis.

PMID- 16655375
TI  - Effects of Gibberellin, Kinetin, Thiourea, and Photomorphogenic Radiation on
      Mitotic Activity in Dormant Lettuce Seed.

PMID- 16655376
TI  - Action of Maleic Hydrazide on Dormancy, Cell Division, and Cell Expansion.

PMID- 16655377
TI  - Effect of Sodium and Potassium Salts on Growth and Oxalate Content of Halogeton.

PMID- 16655378
TI  - Utilization of Exogenous Sugars for Biosynthesis of Carbohydrates in Germinating
      Pollen.

PMID- 16655379
TI  - A Role for Methionine in Division of Chlorella Vulgaris.

PMID- 16655380
TI  - Iron Nutrition of Nicotiana Tabacum L. in Relation to Riboflavin, Riboflavin-5
      phosphate, and Flavin Adenine Dinucleotide Content.

PMID- 16655381
TI  - Influence of Gibberellic Acid on Setting and Development of Fruits in Tomato.

PMID- 16655382
TI  - Influence of Boron on Enzymatic Reactions Associated with Biosynthesis of
      Sucrose.

PMID- 16655383
TI  - Role of Carotenoids in Protecting Chlorophyll From Photodestruction.

PMID- 16655384
TI  - Studies on Cyanogenic Glycoside of Sorghum Vulgare.

PMID- 16655385
TI  - Changes in Certain Nitrogenous Constituents of Winter Wheat as Related to Cold
      Hardiness.

PMID- 16655387
TI  - Absorption of Enzymes and Other Proteins by Barley Roots.

PMID- 16655388
TI  - Action of Gibberellic Acid on Lettuce Seed Germination.

PMID- 16655389
TI  - Binding of Enzymes to Avena Coleoptile Cell Walls.

PMID- 16655390
TI  - Effects of Temperature and Humidity on Foliar Absorption and Translocation of 2,4
      Dichlorophenoxyacetic Acid and Benzoic Acid.

PMID- 16655391
TI  - Effect of Auxin upon Loss of Calcium from Cell Walls.

PMID- 16655392
TI  - Ethionine and Auxin-Action in Avena Coleoptile.

PMID- 16655393
TI  - Apparent Free Space of Plant Roots.

PMID- 16655395
TI  - Some Observations on Absorption of Cesium by Excised Barley Roots.

PMID- 16655394
TI  - Interrelationships of Catalase, Peroxidase, Hematin, and Chlorophyll.

PMID- 16655396
TI  - Simple Method for Continuous Treatment of Plant Material with Metered Traces of
      Ethylene or Other Gases.

PMID- 16655397
TI  - Comparison of Lignin-Like Polymers Produced Peroxidatively by Cinnamic Acid
      Derivatives in Leaf Sections of Phleum.

PMID- 16655398
TI  - Chlorosis in Soybean as Related to Iron, Phosphorus, Bicarbonate, and Cytochrome
      Oxidase Activity.

PMID- 16655399
TI  - Oxidative Enzymes of Spinach Chloroplasts.

PMID- 16655400
TI  - Physiological Studies of Chilling Injury in Citrus Fruits.

PMID- 16655401
TI  - Respiratory Responses to Cations in a Red Alga and Their Relationships to Ion
      Transport.

PMID- 16655402
TI  - Anthocyanin Synthesis in Corn Endosperm Tissue Cultures. II. Effect of Certain
      Inhibitory and Stimulatory Agents.

PMID- 16655403
TI  - Studies in Stomatal Behavior. I. Effects of Moving and Still Air on Stomata of
      Eupatorium and Mentha.

PMID- 16655404
TI  - Effect of Supra-Optimal Boron Levels on Respiration and Carbohydrate Metabolism
      of Helianthus Annuus.

PMID- 16655405
TI  - Influence of Salts on Activity of Malic Dehydrogenase from Spinach Leaves.

PMID- 16655406
TI  - Influence of Certain Cations on Activity of Acetic Thiokinase from Spinach
      Leaves.

PMID- 16655407
TI  - A Carotene Precursor: Its Proposed Structure and Place in Biosynthetic Sequence.

PMID- 16655408
TI  - Some Quantitative Considerations in Iron Nutrition of Higher Plants.

PMID- 16655409
TI  - Demonstration of Two Translocation Mechanisms in Studies of Bidirectional
      Movement.

PMID- 16655410
TI  - Construction of Large Low Cost Filters for Plant Growth Studies.

PMID- 16655411
TI  - Nitrate Reductase Activity in Corn Seedlings as Affected by Light and Nitrate
      Content of Nutrient Media.

PMID- 16655412
TI  - Oxidation and Phosphorylation by Mitochondria from Green Stems.

PMID- 16655413
TI  - Metabolism of Isolated Leaves: I. Changes in the Protein, Soluble Nitrogenous
      Compounds, Sugars, and Organic Acids in Tobacco Leaves in Light and Dark.

PMID- 16655414
TI  - Free Amino Acids in Alfalfa as Related to Cold Hardiness.

PMID- 16655415
TI  - Free Amino Acids in Red Clover as Related to Flowering and Winter Survival.

PMID- 16655416
TI  - Differential Effects of 2,3,6-Trichlorobenzoic Acid on Growth and Geotropic
      Curvature of Avena Coleoptiles.

PMID- 16655417
TI  - Sex Expression and Growth in Muskmelon.

PMID- 16655418
TI  - Role of Glyoxylate in Biosynthesis of Acids in Tomato Fruit.

PMID- 16655419
TI  - Radiorespirometric Studies of Glucose Catabolism in Tomato Fruit.

PMID- 16655420
TI  - Studies on Pyruvate Metabolism and Cytochrome System in Neurospora Tetrasperma.

PMID- 16655421
TI  - Factors Influencing In Vivo Formation of p-Hydroxymandelonitrile-beta-d
      Glucoside.

PMID- 16655422
TI  - Action of Plant Growth Regulators. III. Adsorption of Aromatic Acids to Oat
      Monolayers.

PMID- 16655423
TI  - On the Theory of Osmotic Water Movement.

PMID- 16655424
TI  - Oxidative Activity of Cytoplasmic Particles of Apples: Electron Transfer Chain.

PMID- 16655425
TI  - Activation Spectra of 700 mmu Absorption Change in Photosynthesis.

PMID- 16655426
TI  - Production of Auxotrophs in a Duckweed, Spirodela Polyrhiza.

PMID- 16655427
TI  - Enhancement of Gibberellin Growth-Promoting Activity by Hydrangenol Isolated from
      Leaves of Hydrangea Macrophylla.

PMID- 16655428
TI  - Some Effects of Ammonia on Plant Metabolism and a Possible Mechanism for Ammonia
      Toxicity.

PMID- 16655429
TI  - Accumulation of Potassium, Cesium, and Rubidium in Bean Plants Grown in Nutrient
      Solutions.

PMID- 16655431
TI  - Pentose Phosphate Pathway as a Major Component of Induced Respiration of Carrot
      and Potato Slices.

PMID- 16655430
TI  - Pathways of Glucose Dissimilation in Carrot Slices.

PMID- 16655432
TI  - Penetration of Mannitol into Potato Discs.

PMID- 16655433
TI  - Fat Metabolism in Germinating Soybeans. I. Physiology of Native Fat.

PMID- 16655434
TI  - Mineral Deficiency and Organic Constituents in Tobacco Plants. I. Alkaloids,
      Sugars, and Organic Acids.

PMID- 16655435
TI  - Mineral Deficiency and Organic Constituents in Tobacco Plants. II. Amino Acids.

PMID- 16655436
TI  - 2-Chloroethyl Trimethylammonium Chloride and Related Compounds as Plant Growth
      Substances. V. Growth, Flowering, and Fruiting Responses as Related to Those
      Induced by Auxin and Gibberellin.

PMID- 16655437
TI  - Competition Between Chelating Agents and Roots as Factor Affecting Absorption of
      Iron and Other Ions by Plant Species.

PMID- 16655438
TI  - Biosynthesis of Anabasine and of Nicotine by Excised Root Cultures of Nicotiana
      Glauca.

PMID- 16655439
TI  - Accumulation and Transformation of Sugars in Sugar Cane Stalks.

PMID- 16655440
TI  - Physiological Effects of Gibberellic Acid. II. On Starch Hydrolyzing Enzymes of
      Barley Endosperm.

PMID- 16655441
TI  - Metabolic and Non-Metabolic Uptake of Sodium in Roots of Zea Mays.

PMID- 16655442
TI  - Relative Uptake and Translocation of Potassium and Cesium in Barley.

PMID- 16655443
TI  - Gross Nutritional Contributions of Maize Endosperm and Scutellum to Germination
      Growth of Maize Axis.

PMID- 16655444
TI  - Site of Origin and Extent of Activity of Amylases in Maize Germination.

PMID- 16655445
TI  - Effects of Indoleacetic Acid and Kinetin on Scopoletin-Scopolin Levels in
      Relation to Growth of Tobacco Tissues in Vitro.

PMID- 16655446
TI  - Respiration and Phosphorylation of Mitochondria from Normal and Crown-Gall Tissue
      Cultures of Tomato.

PMID- 16655447
TI  - Translocation of Citrulline in Alnus Glutinosa.

PMID- 16655448
TI  - Light Dosage and Phototropic Responses of Corn and Oat Coleoptiles.

PMID- 16655449
TI  - Relationships Between Time Course, Chromatic Transient, and Enhancement Phenomena
      of Photosynthesis.

PMID- 16655450
TI  - Studies of Rest Period. II. Nitrogen and Phosphorus Changes in Embryonic Organs
      of After-Ripening Cherry Seed.

PMID- 16655451
TI  - Studies of Rest Period. III. Respiratory Changes in Leaf Primordia of Maple Buds
      During Chilling.

PMID- 16655452
TI  - Removal of Heavy Metal and Halide Contamination from Macronutrient Salts.

PMID- 16655453
TI  - Investigation of Hyoscyamus Niger L., A Long-Day Plant, for Endodiurnal
      Periodicity in Flowering Response.

PMID- 16655455
TI  - Anthocyanin production in detached petals of impatiens balsamina L.

PMID- 16655456
TI  - Oligosaccharide production from sucrose by Verticillium albo-atrum.

PMID- 16655458
TI  - Mechanisms by which wind influences transpiration.

PMID- 16655457
TI  - Some effects of tonicity on lupine succinoxidase.

PMID- 16655459
TI  - Action spectra of light-saturated photosynthesis.

PMID- 16655461
TI  - News & notes.

PMID- 16655460
TI  - Cyanide & chelating agent effects on in vitro CO(2) fixation in sweet orange
      leaves.

PMID- 16655462
TI  - Effect of cations on germination & germ tube development of Puccinia coronata
      uredospores.

PMID- 16655463
TI  - Changing respiratory pathways in potato tuber slices.

PMID- 16655464
TI  - Isolation & characterization of malformin.

PMID- 16655465
TI  - Studies on response of bean seedlings & corn roots to malformin.

PMID- 16655466
TI  - Cyclic and non-cyclic photophosphorylation in chloroplasts distinguished by use
      of labeled oxygen.

PMID- 16655468
TI  - Effect of sodium bicarbonate on iron absorption by orange seedlings.

PMID- 16655467
TI  - Naturally occurring growth substances. II. An improved straight growth test & its
      applications.

PMID- 16655469
TI  - Uptake of calcium by excised barley roots.

PMID- 16655470
TI  - Influence of calcium on selectivity of ion absorption process.

PMID- 16655471
TI  - Effect of root to solution ratio in ion absorption experiments.

PMID- 16655472
TI  - Effect of various cations upon absorption of carrier-free cesium.

PMID- 16655473
TI  - Photosynthesis & respiration in developing fruits . II. Comparative rates at
      various stages of development.

PMID- 16655474
TI  - Influence of cobalt on nitrogen fixation by medicago.

PMID- 16655475
TI  - Cytochrome system in Schizophyllum commune.

PMID- 16655476
TI  - Ubiquity of stimulation of endogenous respiration by purines & purine analogs.

PMID- 16655477
TI  - Correlation between inactivation of 2,4-dichlorophenoxyacetic acid & cessation of
      callus growth in bean stem sections.

PMID- 16655478
TI  - Pyrimidine metabolism in germinating seedlings.

PMID- 16655479
TI  - Further studies of synergism in slit pea test.

PMID- 16655480
TI  - Effects of calcium, potassium, & magnesium on oxalic, malic, & citric acid
      content of valencia orange leaf tissue.

PMID- 16655481
TI  - Metabolic fractionation of C & C in plants.

PMID- 16655482
TI  - Analytical study of ipomeamarone & chlorogenic acid alterations in sweet potato
      roots infected by Ceratocystis fimbriata.

PMID- 16655483
TI  - Some effects of 2,4-dichlorophenoxyacetic acid on soluble nucleotides & nucleic
      acid of soybean seedlings.

PMID- 16655484
TI  - Basis of shoot response to root temperature in tomato.

PMID- 16655485
TI  - Nucleotide & ribonucleic acid metabolism of corn seedlings.

PMID- 16655486
TI  - Foliar penetration by chemicals.

PMID- 16655487
TI  - Accumulation & transformation of sugars in stalks of sugar cane. Origin of
      glucose & fructose in the inner space.

PMID- 16655488
TI  - Effects of wax coatings on leaf temperatures & field survival of Pinus taeda
      seedlings.

PMID- 16655489
TI  - Kinetics of rubidium absorption & translocation by barley.

PMID- 16655490
TI  - Effect of 2,4-dichlorophenoxyacetic acid on utilization of labeled acetate by
      bean leaf & stem tissues.

PMID- 16655491
TI  - Production of yellow strapleaf of chrysanthemum & similar disorders by amino acid
      treatment.

PMID- 16655492
TI  - Stimulation of the Hill reaction by carbon dioxide.

PMID- 16655493
TI  - Assimilation of ammonia by nitrogen-starved cells of Chlorella vulgaris.

PMID- 16655494
TI  - Extractability of DNA & its determination in tissues of higher plants.

PMID- 16655495
TI  - DNA Content of broad bean (Vicia faba) internodes in connection with tumor
      induction by Agrobacterium tumefaciens.

PMID- 16655496
TI  - Rapid bioassay for kinetin & kinins using senescing leaf tissue.

PMID- 16655497
TI  - Thiocarbamates as plant growth regulators.

PMID- 16655498
TI  - A naturally occurring chelate of iron in xylem exudate.

PMID- 16655499
TI  - Time course of oxygen evolution during photosynthesis in synchronized cultures of
      algae.

PMID- 16655500
TI  - Pteridines in blue green algae.

PMID- 16655501
TI  - Effect of boron on elongation of tomato root tips.

PMID- 16655502
TI  - Light dependent oxygen metabolism of chloroplast preparations. III.
      Photooxidation of ascorbic acid.

PMID- 16655503
TI  - Variations in starch & total polysaccharide content of Pinus ponderosa needles
      with fluoride fumigation.

PMID- 16655504
TI  - Influence of reproductive organs on secretion of sugars in flowers of
      Streptosolen jamesonii, Miers.

PMID- 16655505
TI  - Entry of phosphate into yeast cell.

PMID- 16655506
TI  - Responses of seeds of Pinus virginiana to light.

PMID- 16655507
TI  - Uptake of magnesium & its interaction with calcium in excised barley roots.

PMID- 16655508
TI  - Translocation & re-use of boron in broccoli.

PMID- 16655509
TI  - Isolation of metabolically-active subcellular particles from etiolated cotton
      seedling hypocotyls using bovine serum albumin in preparative medium.

PMID- 16655510
TI  - Two improved & inexpensive systems for moisture stabilization in seeds or other
      tissues.

PMID- 16655511
TI  - Invertase & invertase inhibitor in potato.

PMID- 16655512
TI  - Mechanism of stimulation of respiration by purines: I. Inhibitor studies.

PMID- 16655513
TI  - Steady state growth of avena coleoptile sections in high auxin concentrations.

PMID- 16655514
TI  - Effect of photochemically produced oxidants on growth of Avena coleoptile
      sections.

PMID- 16655515
TI  - Diffusion of tritiated water into roots as influenced by water status of tissue.

PMID- 16655516
TI  - Cell wall carbohydrates in tobacco pith parenchyma as affected by boron
      deficiency & by growth in tissue culture.

PMID- 16655517
TI  - On the mass culture of algae. III. Light diffusers; high vs low temperature
      Chlorellas.

PMID- 16655518
TI  - Oxidation of reduced diphosphopyridine nucleotide by mitochondria from normal &
      crown-gall tissue cultures of tomato.

PMID- 16655519
TI  - Pigment formation & photosynthesis in dormant lettuce seeds.

PMID- 16655520
TI  - Isolation of indole-3-acetic acid from corn kernels & etiolated corn seedlings.

PMID- 16655521
TI  - News & Notes.

PMID- 16655522
TI  - Influence of 2,3,5-triiodobenzoic acid, indole-3-acetic acid & method of sample
      collection on translocation of foliar applied radiocalcium.

PMID- 16655523
TI  - Mediation of geotropic response by lateral transport of auxin.

PMID- 16655524
TI  - Involvement of adenylate kinase in phosphorylation of ribose-5-phosphate by
      adenosinediphosphate in mitochondria-free preparations from rough lemon leaves.

PMID- 16655525
TI  - An estimate of a minimum quantum yield of photosynthesis based on ecologic data.

PMID- 16655526
TI  - Carbon dioxide fixation by auxin treated tissues.

PMID- 16655527
TI  - Mechanism (s) of fluoride induced chlorosis.

PMID- 16655528
TI  - Fruit-induced & apical senescence in Pisum sativum L.

PMID- 16655529
TI  - Photosynthesis & transpiration from upper & lower surfaces of intact banana
      leaves.

PMID- 16655530
TI  - Reaction of gibberellic acid & gibberellins with Folin-Wu phosphomolybdic acid
      reagent & its use for quantitative assay.

PMID- 16655531
TI  - The reductive pentose phosphate cycle. III. Enzyme activities in cell-free
      extracts of photosynthetic organisms.

PMID- 16655532
TI  - Chlorosis in higher plants as related to organic acid content.

PMID- 16655533
TI  - Distribution of boron in leaves.

PMID- 16655534
TI  - Effect of soil oxygen deficit on iron nutrition of orange seedlings.

PMID- 16655535
TI  - Transpiration stream & ascension of calcium.

PMID- 16655536
TI  - The essential role of calcium in selective cation transport by plant cells.

PMID- 16655537
TI  - Effects of salts on DPNH oxidase activity & structure of sweet potato
      mitochondria.

PMID- 16655538
TI  - Comparative study of phototropic response & pigment content in oat & barley
      coleoptiles.

PMID- 16655539
TI  - Maleic hydrazide-auxin interractions in water uptake of potato discs.

PMID- 16655540
TI  - Osmotic & specific effects of excess salts on beans.

PMID- 16655541
TI  - Salt tolerance & protoplasmic salt hardiness of various woody & herbaceous
      ornamental plants.

PMID- 16655542
TI  - Suspension cultures of higher plant cells in synthetic media.

PMID- 16655543
TI  - Hexitols in coconut milk: Their role in nurture of dividing cells.

PMID- 16655544
TI  - Mass adaptation to selenomethionine in populations of Chlorella vulgaris.

PMID- 16655546
TI  - News & notes.

PMID- 16655545
TI  - Stability & reversibility of adaptation to selenomethionine in Chlorella
      vulgaris.

PMID- 16655548
TI  - A note on efficiency of photon absorption.

PMID- 16655547
TI  - Mechanisms & reversal of gametocide response in cotton.

PMID- 16655549
TI  - Formation of sucrose from malate in germinating castor beans. I. Conversion of
      malate to phosphoenol-pyruvate.

PMID- 16655550
TI  - Further studies on a particulate enzyme preparation from nodules of soybean
      plants.

PMID- 16655551
TI  - Effects of ethylene & oxygen on production of a bitter compound by carrot roots.

PMID- 16655552
TI  - Preparation & some properties of soluble succinic dehydrogenase from higher
      plants.

PMID- 16655553
TI  - Metabolites of 2,4-dichlorophenoxyacetic acid from bean stems.

PMID- 16655554
TI  - Effects of X irradiation on corn seed.

PMID- 16655555
TI  - Effects of moisture stress on absorption, translocation, & distribution of 2,4
      dichlorophenoxyacetic acid in bean plants.

PMID- 16655556
TI  - Photosynthesis & transpiration of banana leaves as affected by severing the
      vascular system.

PMID- 16655557
TI  - Selective translocation of products of photosynthesis in soybean.

PMID- 16655558
TI  - Auxin-phenol complexes.

PMID- 16655559
TI  - Conversion of nicotine to nornicotine in harvested tobacco: Fate of the methyl
      group.

PMID- 16655560
TI  - Studies in valine biosynthesis: II. Enzymatic dehydration of alpha,beta
      dihydroxyisovaleric acid by plant extracts.

PMID- 16655561
TI  - Enzymatic activities associated with cell wall preparations from corn
      coleoptiles.

PMID- 16655562
TI  - Sulfhydryls-a new factor in frost resistance. I. Changes in SH content during
      frost hardening.

PMID- 16655563
TI  - Sulfhydryls-a new factor in frost resistance. II. Relation between sulfhydryls &
      relative resistance of 15 wheat varieties.

PMID- 16655564
TI  - Growth of Parthenocissus tricuspidata tissue cultured on media containing aza
      analogues of indole-3-acetic acid & indole-3-propionic acid.

PMID- 16655565
TI  - Critical phosphorus levels for lima bean growth.

PMID- 16655566
TI  - Negative transport & resistance to water flow through plants.

PMID- 16655567
TI  - Effect of temperature on water transport through plants.

PMID- 16655568
TI  - Dormancy in Betula as a quantitative state.

PMID- 16655569
TI  - Certain properties of hypocotyl of Impatiens balsamina reflecting physiological
      complexity.

PMID- 16655570
TI  - Persistence & transport of flowering stimulus in Xanthium.

PMID- 16655571
TI  - Responses to gibberellin of light-requiring seeds of lettuce & Lepidium
      virginicum.

PMID- 16655572
TI  - A relationship between boron & auxin in C translocation in bean plants.

PMID- 16655573
TI  - Rapid cryoscopic technique for measuring osmotic properties of drop size samples.

PMID- 16655574
TI  - Effects of thermoperiodism on tuber formation in Ipomoea batatas under controlled
      conditions.

PMID- 16655575
TI  - Interaction of gibberellic acid & allyl trimethylammonium bromide upon growth of
      Ulothrix.

PMID- 16655576
TI  - Absorption, distribution, & metabolism of 2,2-dichloropropionic acid in relation
      to phytotoxicity. I. Penetration & translocation of Cl- and C-labeled dalapon.

PMID- 16655577
TI  - Absorption, distribution, & metabolism of 2,2-dichloropropionic acid in relation
      to phytotoxicity. II. Distribution & metabolic fate of dalapon in plants.

PMID- 16655579
TI  - News & notes.

PMID- 16655578
TI  - Selective absorption of iron from iron chelates by soybean plants.

PMID- 16655580
TI  - Translocated heat injury.

PMID- 16655581
TI  - Growth & geotropic curvature of Avena coleoptiles in presence of n-1
      naphthylphthalamic acid.

PMID- 16655582
TI  - Red, far-red response & chlorophyll synthesis.

PMID- 16655583
TI  - Effect of iron chlorosis on protein fractions of corn leaf tissue.

PMID- 16655584
TI  - Germination inhibitors related to dormancy in wheat seeds.

PMID- 16655585
TI  - Identification & mode of action of a component of positively-ionized air causing
      enhanced growth in plants.

PMID- 16655586
TI  - An inhibitor of indoleacetic acid oxidase from pea tips.

PMID- 16655587
TI  - Assimilation of C, N labeled urea by excised apple & peach leaves.

PMID- 16655588
TI  - Effect of soil moisture stress on absorption & translocation of phosphorus
      applied to leaves of sunflower.

PMID- 16655589
TI  - Uptake of calcium & chlorine in roots of Zea mays.

PMID- 16655590
TI  - Changes in nitrogen metabolism in sweet potato with black rot.

PMID- 16655591
TI  - Studies on 3-indoleacetic acid metabolism. VII. Metabolism of radioactive 3
      indoleacetic acid by pea roots.

PMID- 16655592
TI  - Inhibitors of the Hill reaction.

PMID- 16655593
TI  - Oxidative activity of cytoplasmic particles of apples: Krebs cycle oxidations,
      oxidative phosphorylation, & cytochromes.

PMID- 16655594
TI  - Deoxyribonucleic acid of cotton.

PMID- 16655595
TI  - Physiological effects & degradation of S,S,S-tributylphosphorotri-thioate by
      cotton leaves as shown by the P & S labeled compounds.

PMID- 16655596
TI  - Carbohydrate translocation in raspberry & soybean.

PMID- 16655597
TI  - Western X-little cherry virus effects on respiration of host tree.

PMID- 16655598
TI  - Physiological effects of gibberellic acid. III. Observations on its mode of
      action on barley endosperm.

PMID- 16655600
TI  - News & Notes.

PMID- 16655599
TI  - Formation of auxin from tryptophan through action of polyphenols.

PMID- 16655601
TI  - Role of Hexose Monophosphate Pathway in Tomato Catabolism.

PMID- 16655602
TI  - Senescence Factor & Abscission of Coleus Leaves.

PMID- 16655603
TI  - Effects of Indoleacetic Acid on Growth Without Mitosis & on Mitotic Activity in
      Absence of Growth by Expansion.

PMID- 16655604
TI  - Preparing Whole-Leaf Radioautographs for Studying Translocation.

PMID- 16655605
TI  - Ethylene Production, Respiration, & Internal Gas Concentrations in Cantaloupe
      Fruits at Various Stages of Maturity.

PMID- 16655606
TI  - Effects of Temperature & Illuminance on Chlorella Growth Uncoupled From Cell
      Division.

PMID- 16655607
TI  - Ribonucleic Acid Synthesis in the Bud Essential Component of Floral Induction in
      Xanthium.

PMID- 16655608
TI  - Induction of Disease Symptoms in Barley by Powdery Mildew.

PMID- 16655609
TI  - Growth Promoting Effect of Cyclitols on Spruce Tissue Cultures.

PMID- 16655610
TI  - Effects of 2,4-Dichlorophenoxyacetic Acid on Enzymes of Glycolysis & Pentose
      Phosphate Cycle.

PMID- 16655611
TI  - An IAA Oxidase-Inhibitor System in Bean Pods. II. Kinetic Studies of Oxidase &
      Natural Inhibitor.

PMID- 16655612
TI  - Phosphorylation by Barley Root Mitochondria & Phosphate Absorption by Barley
      Roots.

PMID- 16655613
TI  - Fatty Acids of Spinach Chloroplasts.

PMID- 16655614
TI  - Condensing Enzyme from Higher Plants.

PMID- 16655615
TI  - Cytochrome Components & Electron Transfer in Sweet Potato Mitochondria.

PMID- 16655617
TI  - Heat Transfer Analysis of Factors Affecting Plant Leaf Temperature. Significance
      of Leaf Hair.

PMID- 16655616
TI  - Chemical Nature of an Insect Gall Growth-Factor.

PMID- 16655618
TI  - Fat Metabolism in Higher Plants. XVII. Metabolism of Malonic Acid & Its alpha
      Substituted Derivatives in Plants.

PMID- 16655619
TI  - Photooxidase Activity of Heated Chromatophores of Rhodospirillum rubrum.

PMID- 16655620
TI  - Influence of Hormones on Respiratory Metabolism of Healthy & Rust-Affected
      Tissues.

PMID- 16655621
TI  - Uncoupling Phosphorylation in Spinach Chloroplasts by Absence of Cations.

PMID- 16655622
TI  - Photomorphogenetic Responses of Sporelings of Marsilea vestita.

PMID- 16655623
TI  - Physiology of Flowering in Peas.

PMID- 16655624
TI  - Effects of Magnesium Concentrations on in Vitro CO(2) Fixing Reactions.

PMID- 16655625
TI  - Growth Promotion in Pea Stem Sections. II. By Natural Oils & Isoprenoid Vitamins.

PMID- 16655626
TI  - Interaction of Photoperiod & Vernalization in Flowering of Sweet Clover
      (Melilotus).

PMID- 16655627
TI  - Formation of beta-Alanine by Pine Tissues Supplied With Intermediates in Uracil &
      Orotic Acid Metabolism.

PMID- 16655628
TI  - Formation of Sucrose From Malate in Germinating Castor Beans . II. Reaction
      Sequence From Phosphoenol-Pyruvate to Sucrose.

PMID- 16655629
TI  - Role of Ethylene in Fruit Ripening.

PMID- 16655630
TI  - Temperature Control of Physiological Dwarfing in Peach Seedlings.

PMID- 16655631
TI  - Differential Cation & Anion Absorption as Affected by Climate.

PMID- 16655632
TI  - Effects of Calcium, Indoleacetic Acid & Distance From Stem Apex on Potassium &
      Rubidium Absorption by Excised Segments of Etiolated Pea Epicotyl.

PMID- 16655633
TI  - Effects of Plant Growth Regulators & Herbicides on Metabolism of C-Labeled
      Acetate in Pea Root Tissues.

PMID- 16655634
TI  - Growth Inhibition & Bleaching in Higher Plants & Euglena by O-Methylthreonine;
      Reversal by Isoleucine.

PMID- 16655635
TI  - Responses of Seeds of Pinus taeda & P. strobus to Light.

PMID- 16655636
TI  - Effect of Various Herbicides on Glucose Metabolism in Root Tissue of Garden Peas,
      Pisum sativum. I. 2,4-Dichlorophenoxyacetic Acid & Its Analogs.

PMID- 16655637
TI  - Riboflavin Nullification of Inhibitory Actions of 3-Amino-1,2,4-Triazole on
      Seedling Growth.

PMID- 16655638
TI  - Physiological Nature of Gene-Controlled Growth Form in Trifolium fragiferum L.
      II. Auxin-Gibberellin Relationships to Growth Form.

PMID- 16655639
TI  - News & Notes.

PMID- 16655640
TI  - Genetic Tumors of Nicotiana. I. Chemical Composition of N. glauca, N.
      langsdorffii, & Their F(1) Hybrid.

PMID- 16655641
TI  - Protection of Plants Against Airborne Oxidants: Cucumber Seedlings at Extreme
      Ozone Levels.

PMID- 16655642
TI  - Sulfhydryls-A New Factor in Frost Resistance. III. Relation of SH Increase During
      Hardening to Protein, Glutathione, & Glutathione Oxidizing Activity.

PMID- 16655643
TI  - Sulfhydryls-A New Factor in Frost Resistance. IV. Relation of GSH-Oxidizing
      Activity to Flower Induction & Hardiness.

PMID- 16655644
TI  - Effect of Puccinia graminis tritici on Organic Acid Content of Wheat Leaves.

PMID- 16655645
TI  - Diurnal Variations in Some Enzymes of Carbohydrate Metabolism in Tapioca Leaves.

PMID- 16655646
TI  - Measurement of Energy Status of Water in Plants With a Thermocouple Psychrometer.

PMID- 16655647
TI  - Electrophoretic Patterns of Xanthium Leaf Extracts as Affected by Physiological
      Age of Leaf, Photoperiod, & Age of Plant.

PMID- 16655648
TI  - DNA Multiplication as a Requirement for Expression of Floral Stimulus in
      Pharbitis nil.

PMID- 16655649
TI  - Effect of Fluoride on Glucose Catabolism in Plant Leaves.

PMID- 16655650
TI  - Metabolism of Pyruvate by Starved Cells of Chlorella elipsoida.

PMID- 16655651
TI  - Influence of Glucose & Light on Pyruvate Metabolism by Starved Cells of Chlorella
      elipsoida.

PMID- 16655652
TI  - Glutamine Synthesis & Translocation in Pine.

PMID- 16655653
TI  - Influence of Light on Phosphate Metabolism in Lettuce Seed: Spectral Response
      Red, Far-Red Interaction.

PMID- 16655654
TI  - Apparatus for Growing Plants With Aseptic Roots for Collection of Root Exudates &
      CO(2).

PMID- 16655655
TI  - Invertase in Cell Walls of Plant Tissue Cultures.

PMID- 16655656
TI  - Changes in Ascorbic Acid Metabolism Associated With Auxin-Induced Growth.

PMID- 16655657
TI  - Soxhlet-Type Automatic Sand Cultures.

PMID- 16655658
TI  - Leaf Abscission Induced by the Iodide Ion.

PMID- 16655659
TI  - Response of Oxidation & Coupled Phosphorylation in Plant Mitochondria to 2,4
      Dichlorophenoxyacetic Acid.

PMID- 16655660
TI  - Diurnal Variation in Root Respiration.

PMID- 16655661
TI  - Interrelationship Between Photoperiodic Behavior of Grapes & Growth of Plant
      Tissue Cultures.

PMID- 16655662
TI  - Auxin-Gibberellin Interaction in Rice Coleoptile Elongation.

PMID- 16655663
TI  - Growth in Tissue Culture of Single-Cell Clones From Grape Stem & Phylloxera Gall.

PMID- 16655664
TI  - Measuring Transpiration of Undisturbed Tamarisk Shrubs.

PMID- 16655665
TI  - Effects of Amino Acids on Bean Leaf Abscission.

PMID- 16655667
TI  - A Note on Efficiency for Conversion of Light Energy.

PMID- 16655666
TI  - Role of Aldolase in Photosynthesis. I. Enzyme Studies With Photosynthetic
      Organisms With Special Reference to Blue-Green Algae.

PMID- 16655668
TI  - Carbon Dioxide Effects on Fruit Respiration. I. Measurement of Oxygen Uptake in
      Continuous Gas Flow.

PMID- 16655669
TI  - Carbon Dioxide Effects on Fruit Respiration . II. Response of Avocados, Bananas,
      & Lemons.

PMID- 16655670
TI  - Zinc, Growth, & Respiration in Euglena.

PMID- 16655671
TI  - Euglena gracilis, A Test Organism for Study of Zinc.

PMID- 16655672
TI  - Formation & Elimination of Ethanol in Sugar Beet Roots.

PMID- 16655673
TI  - Indole Compounds Synthesized by Diplodia natalensis.

PMID- 16655675
TI  - News & Notes.

PMID- 16655674
TI  - Sodium Chloride Effect on Dark Fixation of CO(2) by Marine & Terrestrial Plants.

PMID- 16655676
TI  - F. G. Gregory 1893-1961.

PMID- 16655677
TI  - An Unusual Stem Bending Response of Xanthium pensylvanicum to Horizontal
      Rotation.

PMID- 16655678
TI  - Absorption of Chelated Iron by Soybean Roots in Nutrient Solutions.

PMID- 16655679
TI  - Kinetic Studies on Growth of Excised Root Tips of Lycopersicum esculentum.

PMID- 16655680
TI  - Effect of Chloramphenicol on Light Dependent Development of Seedlings of
      Phaseolus vulgaris var. Black Valentine, With Particular Reference to Development
      of Photosynthetic Activity.

PMID- 16655681
TI  - Rapid Changes in Permeability of Cell Membranes to Water Brought About by Carbon
      Dioxide & Oxygen.

PMID- 16655682
TI  - Stomatal Action in Plants as Related to Damage From Photochemical Oxidants.

PMID- 16655683
TI  - Some Characteristics of Movement of Indoleacetic Acid in Coleoptiles of Avena. I.
      Uptake, Destruction, Immobilization, & Distribution of IAA During Basipetal
      Translocation.

PMID- 16655684
TI  - Potentiometrically Measured Reduction of Low Concentrations of Dye by Illuminated
      Chloroplasts.

PMID- 16655685
TI  - Effect of N-Benzylaminopurine on Respiration & Storage Behavior of Broccoli
      (Brassica oleracea var. italica).

PMID- 16655687
TI  - Effect of Maturity & Storage on Distribution of Phosphorus Among Starch & Other
      Components of Potato Tuber.

PMID- 16655686
TI  - Use of Carbowaxes (Polyethylene Glycols) as Osmotic Agents.

PMID- 16655688
TI  - Properties of Transaminases in Tissues of the Pear.

PMID- 16655689
TI  - Translocation of Organic Substances in Trees. V. Experimental Double Interruption
      of Phloem in White Ash (Fraxinus americana L.).

PMID- 16655690
TI  - Carbohydrate Metabolism in Higher Plant Tissues Infected With Obligate Parasites.

PMID- 16655691
TI  - Iron Transport in Pea Plants.

PMID- 16655692
TI  - Iron Localization in Pea Plants.

PMID- 16655693
TI  - Kinetin & Kinetin Analogues as Substrates & Inhibitors of Xanthine Oxidase.

PMID- 16655694
TI  - Nucleotide Incorporation Into Nucleic Acid by Tobacco Leaf Homogenates.

PMID- 16655695
TI  - Protein, Nucleotide, & Ribonucleid Acid Metabolism in Corn During Germination
      Under Water Stress.

PMID- 16655696
TI  - Changes in Ribonucleic Acid & Deoxyribonucleic Acid in Developing Orange Leaves.

PMID- 16655697
TI  - Physiological Effects of Gibberellic Acid. IV. On Barley Grain With Normal, X
      Irradiated, & Excised Embryos.

PMID- 16655698
TI  - Quantitative Measurement of Leaf Chlorophylls by Spectrophotometry of Their
      Pheophytins in Aqueous Alcoholic Extracts.

PMID- 16655699
TI  - Evidence for Absence of Diurnal Variation of Chlorophyll Content in Mature Leaves
      of Soybean.

PMID- 16655700
TI  - Effect of Kinetin on Protein & Nucleic Acid Metabolism in Xanthium Leaves During
      Senescence.

PMID- 16655701
TI  - Effect of Peroxyacetyl Nitrate on Growth & Cell Wall Metabolism of Avena
      Coleoptile Sections.

PMID- 16655702
TI  - Effects of High Humidity on Translocation of Foliar-Applied Labeled Compounds in
      Plants Part: I.

PMID- 16655703
TI  - Metabolism of Urea & Ornithine Cycle Intermediates by Nitrogen-Starved Cells of
      Chlorella vulgaris.

PMID- 16655704
TI  - Regreening of Valencia Orange as Influenced by Potassium Gibberellate.

PMID- 16655705
TI  - Ribonucleic Acid-Polyphosphate From Algae. I. Isolation & Physiology.

PMID- 16655706
TI  - On the Pigment Absorbing at 750 mmu Occurring in Some Blue-Green Algae.

PMID- 16655707
TI  - Protein Turnover Rate in Bean Leaf Disks.

PMID- 16655708
TI  - Histochemical & Biochemical Differences Between Lignin-Like Materials in Phleum
      pratense L.

PMID- 16655709
TI  - Ion Competition in Manganese Uptake by Barley Plants.

PMID- 16655710
TI  - Oxidation of Menadiol by Fractions Isolated From Non-Photosynthetic Plant
      Tissues.

PMID- 16655711
TI  - Pattern of Carbohydrate Breakdown in Sweet Potato Roots Infected With
      Ceratocystis fimbriata.

PMID- 16655712
TI  - Nucleic Acid Determination in Storage Tissues of Higher Plants.

PMID- 16655713
TI  - Controlling Influence of Thickness on Development & Type of Respiratory Activity
      in Potato Slices.

PMID- 16655714
TI  - Effect of Malformin on Respiration & Metabolism of Phaseolus vulgaris L. & Zea
      mays L.

PMID- 16655715
TI  - Effects of High Temperatures on Dry Seeds.

PMID- 16655716
TI  - News & Notes.

PMID- 16655717
TI  - Effects of temperature & light intensity on CO(2) uptake, respiration, & growth
      of white clover.

PMID- 16655718
TI  - Photosynthetic & respiratory activities of growing pea leaves.

PMID- 16655719
TI  - Salt balance in mangroves.

PMID- 16655720
TI  - Glycolic acid oxidase formation in greening leaves.

PMID- 16655721
TI  - An endogenous rhythm in the rate of carbon dioxide output of Bryophyllum. IV.
      Effect of intensity of illumination on entrainment of the rhythm by cycles of
      light & darkness.

PMID- 16655722
TI  - Ascorbic acid oxidase of Myrothecium verrucaria.

PMID- 16655723
TI  - Respiratory changes in barley leaves produced by single colonies of powdery
      mildew.

PMID- 16655724
TI  - Kinetic studies of certain anti-gibberellins.

PMID- 16655725
TI  - Measurement of nicotinamide adenine dinucleotide & nicotinamide adenine
      dinucleotide phosphate in tomato leaves.

PMID- 16655726
TI  - Effect of uracil, thiouracil, & guanine on cold resistance & nitrogen metabolism
      of alfalfa.

PMID- 16655727
TI  - Acid & neutral gibberellin-like substances in potato tubers.

PMID- 16655728
TI  - Factors affecting oxidative phosphorylation by subcellular particles isolated
      from cotton seedling hypocotyls.

PMID- 16655729
TI  - Floral inhibition in relation to photoperiodism in Biloxi soybean.

PMID- 16655730
TI  - Some properties of phloem exudate collected from root of sugar beet.

PMID- 16655731
TI  - Potato tuber tissue respiration & ventilation.

PMID- 16655732
TI  - Physiological effects of gibberellic acid. V. Endosperm responses of barley,
      wheat, & oats.

PMID- 16655733
TI  - Mineral deficiency & organic constituents in tobacco plants. III. Plant growth &
      alkaloid contents related to gradual development of calcium or boron deficiency
      symptoms.

PMID- 16655734
TI  - Relationships among cold hardiness, water-soluble protein, anthocyanins, & free
      sugars in Hedera helix L.

PMID- 16655735
TI  - Studies of growth & metabolism of a barley mutant lacking chlorophyll b.

PMID- 16655736
TI  - Buffering effects of benzimidazole in absorption of potassium by excised barley
      roots.

PMID- 16655737
TI  - Carbon metabolism of C-labeled amino acids in wheat leaves. I. A pathway of
      glyoxylate-serine metabolism.

PMID- 16655739
TI  - News & notes.

PMID- 16655738
TI  - Transformations of labeled formic acid, formaldehyde, methanol, & CO(2) absorbed
      by bean & barley leaves from air.

PMID- 16655740
TI  - Further Improvements in Stationary Platinum Electrode of Haxo & Blinks.

PMID- 16655741
TI  - Enhancement in Chlorella.

PMID- 16655742
TI  - Inactivity of Hexitols & Hexoses in Biosynthesis of Auxin From Tryptophan.

PMID- 16655743
TI  - Acetate Utilization by Maize Roots.

PMID- 16655745
TI  - News & Notes.

PMID- 16655744
TI  - Independence of Effects of Auxin on Cell Wall Methylation & Elongation.

PMID- 16655746
TI  - Mode of Action of Growth Retarding Chemicals.

PMID- 16655747
TI  - Photocontrol of Anthocyanin Synthesis in Milo Seedlings.

PMID- 16655748
TI  - Spectrophotometric Estimation of Nucleic Acid of Plant Leaves.

PMID- 16655749
TI  - Design of a Rotary Shaking Machine.

PMID- 16655750
TI  - Kinetic Studies of Anion Absorption by Potato Slices at 0 C.

PMID- 16655751
TI  - Pyridine Nucleotide Content in the Higher Plant. Effect of Age of Tissue.

PMID- 16655752
TI  - Effects of Non-Ionizing Radiation on Expansion of Disks From Leaves of Dark-Grown
      Bean Plants.

PMID- 16655753
TI  - Identification of Cobamide Coenzyme in Nodules of Symbionts & Isolation of the
      B(12) Coenzyme From Rhizobium meliloti.

PMID- 16655754
TI  - Uptake of Dinitrophenol & its Effect on Transpiration & Calcium Accumulation in
      Barley Seedlings.

PMID- 16655755
TI  - Demonstration of Photophosphorylation by Maize Chloroplasts.

PMID- 16655756
TI  - Iron Uptake-Transport of Soybeans as Influenced by Other Cations.

PMID- 16655757
TI  - Morphogenetic Influence of (CO(2) + HCO(3)) on Roots.

PMID- 16655758
TI  - Suppression of Floral Induction by Inhibitors of Steroid Biosynthesis.

PMID- 16655759
TI  - Senescence of Cotyledons of Germinating Peas. Influence of Axis Tissue.

PMID- 16655760
TI  - Growth-Modifying & Antimetabolite Effects of Amino Acids on Chrysanthemum.

PMID- 16655761
TI  - Cobamide Coenzyme Contents of Soybean Nodules & Nitrogen Fixing Bacteria in
      Relation to Physiological Conditions.

PMID- 16655762
TI  - A Chromatographic-Spectrophotometric Method for Determining Nucleotide
      Composition of RNA in Plants.

PMID- 16655763
TI  - Intracellular Distribution of Proteins in Pea Cotyledons.

PMID- 16655764
TI  - Auxin Factor in Branch Epinasty.

PMID- 16655765
TI  - Observations on Enhancement & Inhibition by Light of Triphosphopyridine
      Nucleotide Photoreduction in Preparations of Laurencia obtusa (Hudson) Lam.

PMID- 16655766
TI  - Kinetics of Malic Dehydrogenase Inhibition by 2,4-Dichlorophenoxyacetic Acid.

PMID- 16655767
TI  - Some Factors Influencing Activity of 12 Phenoxy Acids on Mesquite Root
      Inhibition.

PMID- 16655768
TI  - Effect of Temperature on Infection of Isolated Bean Roots by Rhizobia.

PMID- 16655769
TI  - Temperature-Induced Chemical Defects in Higher Plants.

PMID- 16655770
TI  - Uptake of Strontium by Roots of Zea Mays.

PMID- 16655771
TI  - Glycolate Excretion & Uptake by Chlorella.

PMID- 16655772
TI  - Effect of Oxygen Tension on the Course of Ethylene- & Gibberellin-Induced Foliar
      Abscission.

PMID- 16655773
TI  - Stem Pigmentation in Lowbush Blueberry.

PMID- 16655774
TI  - Respiration & Internal Atmosphere of Avocado Fruit.

PMID- 16655775
TI  - Metabolism of Sinapine in Mustard Plants. I. Degradation of Sinapine into Sinapic
      Acid & Choline.

PMID- 16655776
TI  - Metabolism of Sinapine in Mustard Plants. II. Purification & Some Properties of
      Sinapine Esterase.

PMID- 16655777
TI  - Transport & Distribution of Auxin during Tropistic Response. I. The Lateral
      Migration of Auxin in Geotropism.

PMID- 16655778
TI  - News & Notes.

PMID- 16655779
TI  - Mediation of Phototropic Responses of Corn Coleoptiles by Lateral Transport of
      Auxin.

PMID- 16655780
TI  - Phototropic Dosage-Response Curves for Oat Coleoptiles.

PMID- 16655781
TI  - A Kinetic Model for Phototropic Responses of Oat Coleoptiles.

PMID- 16655782
TI  - Analysis of the Auxin Control of Bean Leaf Abscission.

PMID- 16655783
TI  - Auxin Structure & Abscission Activity.

PMID- 16655784
TI  - Sensitization of Chloroplast Reactions. I. Sensitization of Reduction & Oxidation
      of Cytochrome C by Chloroplasts.

PMID- 16655785
TI  - Carbohydrate Metabolism of Avocado. II. Formation of Sugars during Short Periods
      of Photosynthesis.

PMID- 16655786
TI  - Photosynthesis & Respiration in Developing Fruits. III. Variations in
      Photosynthetic Capacities during Color Change in Citrus.

PMID- 16655787
TI  - Auxin-Kinetin Interaction in Tissue Cultures of Nicotiana Species & Tumor
      Conditioned Hybrids.

PMID- 16655788
TI  - Carbon Dioxide & the Hill Reaction.

PMID- 16655789
TI  - Translocation of C in Sugarcane.

PMID- 16655790
TI  - Nicotinic Acid-Ricinine Relationship in Sterile Cultures of Ricinus communis L.

PMID- 16655791
TI  - Action Spectra of O(2) Evolution by Chloroplasts with & without Added Substrate,
      for Regeneration of O(2) Evolving Ability by Far-red, & for O(2) Uptake.

PMID- 16655792
TI  - Citrus Fruit Enzymes. I. Ascorbic Acid Oxidase in Oranges.

PMID- 16655793
TI  - Sugar Accumulation Cycle in Sugar Cane. I. Studies on Enzymes of the Cycle.

PMID- 16655794
TI  - Sugar Accumulation Cycle in Sugar Cane. II. Relationship of Invertase Activity to
      Sugar Content & Growth Rate in Storage Tissue of Plants Grown in Controlled
      Environments.

PMID- 16655795
TI  - Sugar Accumulation Cycle in Sugar Cane. III. Physical & Metabolic Aspects of
      Cycle in Immature Storage Tissues.

PMID- 16655797
TI  - News & Notes.

PMID- 16655796
TI  - Localization of Carboxydismutase & Triosephosphate Dehydrogenases in
      Chloroplasts.

PMID- 16655798
TI  - Harry A. Allard 1880-1963.

PMID- 16655799
TI  - Indoleacetic Acid Oxidizing Enzyme & Inhibitors from Light-Grown Cotton.

PMID- 16655800
TI  - Carbon Monoxide Production by Algae.

PMID- 16655801
TI  - Ethanol Metabolism in Plant Tissues.

PMID- 16655802
TI  - Allagochrome. I. Properties, Purification, & Assay Procedures.

PMID- 16655803
TI  - Some Effects of Metabolic Inhibitors, Temperature, & Anaerobic Conditions on
      Stomatal Movement.

PMID- 16655804
TI  - Effect of Potassium & Other Univalent Cations on Activity of Pyruvate Kinase in
      Pisum sativum.

PMID- 16655805
TI  - Effect of Aluminum on Uptake & Translocation of Phosphorus by Perennial Ryegrass.

PMID- 16655806
TI  - Effects on Zea mays Seedlings of a Strontium Replacement for Calcium in Nutrient
      Media.

PMID- 16655807
TI  - Detection of Phytochrome in Green Plants.

PMID- 16655808
TI  - Inhibition of Metabolism in Avena Coleoptile Tissue by Fluoride.

PMID- 16655809
TI  - Kinetics of Rb Absorption by Excised Barley Roots under Changing Rb
      Concentrations. I. Effects of Other Cations on Rb Uptake.

PMID- 16655810
TI  - Auxin Induced Product Inhibition of Pectin Transeliminase as Shown by Ozonolysis.

PMID- 16655811
TI  - Carbon Metabolism of C-Labeled Amino Acids in Wheat Leaves. II. Serine & its Role
      in Glycine Metabolism.

PMID- 16655812
TI  - Nucleic Acid, Mitochondria, & Enzyme Changes in Cotyledons of Peanut Seeds during
      Germination.

PMID- 16655813
TI  - Formation of Anthocyanin in Leaves of Kalanchoe blossfeldiana-a Photoperiodic
      Response.

PMID- 16655814
TI  - Subcellular Distribution of alpha-Tocopherol in Spinach & Lilac Leaf Tissue.

PMID- 16655815
TI  - Partial Purification & Properties of Xylose & Ribose Isomerase in Higher Plants.

PMID- 16655816
TI  - Permeability of Apricot Leaf Cuticle.

PMID- 16655817
TI  - Effect of Peroxyacetyl Nitrate on CO(2) Fixation by Spinach Chloroplasts & Pinto
      Bean Plants.

PMID- 16655819
TI  - Photoperiodic Responses of Two Cestrum Species and Non-Interchangeability of
      Their Flowering Hormones.

PMID- 16655818
TI  - Ether-Soluble & Ether-Insoluble Auxins from Immature Corn Kernels.

PMID- 16655820
TI  - Inhibitor Studies on Carbon Dioxide Fixation, Adenosine Triphosphate Formation, &
      Triphosphopyridine Nucleotide Reduction by Spinach Chloroplasts.

PMID- 16655821
TI  - Analytical Study of Umbelliferone and Scopoletin Synthesis in Sweet Potato Roots
      Infected by Ceratocystis fimbriata.

PMID- 16655822
TI  - Nicotinamide Adenine Dinucleotide in Potato Tuber Slices in Relation to
      Respiratory Changes with Age.

PMID- 16655823
TI  - Effects of High Humidity on Translocation of Foliar-applied Labeled Compounds in
      Plants. II. Translocation from Starved Leaves.

PMID- 16655824
TI  - Banana Polyphenoloxidase. Preparation and Properties.

PMID- 16655825
TI  - Nonphotochemical Transformations of Phytochrome in Vivo.

PMID- 16655826
TI  - Influence of Chilling upon Seedling Development of Cotton.

PMID- 16655827
TI  - Studies of Effects of Light on Growth Pattern and of Gibberellin Sensitivity in
      Relation to Age, Growth Rate, and Illumination in Intact Wheat Coleoptiles.

PMID- 16655828
TI  - Spore Germination and Carbon Metabolism in Fusarium solani. III. Carbohydrate
      Respiration in Relation to Germination.

PMID- 16655829
TI  - Photosynthetic Reactions by Chloroplast Fragments of Chlamydomonas reinhardi.

PMID- 16655830
TI  - The Dependence of Auxin-induced Growth on Auxin-independent Metabolic Changes in
      Slices of Storage Tissue.

PMID- 16655831
TI  - Utilization of Labeled Glucose in Developing Douglas Fir Seed Cones.

PMID- 16655832
TI  - Evidence for Substances in Higher Plants Interfering with Response of Dwarf Peas
      to Gibberellin.

PMID- 16655833
TI  - Nitrogen Mobilization in Pea Seedlings. II. Free Amino Acids.

PMID- 16655834
TI  - Auxin Transport in Leaf Epinasty.

PMID- 16655835
TI  - The Influence of Light on Synthesis of Protein and of Chlorogenic Acid in Potato
      Tuber Tissue.

PMID- 16655836
TI  - Relationship of Cell Transmembrane Electropotential to Potassium and Sodium
      Accumulation Ratios in Oat and Pea Seedlings.

PMID- 16655837
TI  - Turnover Rates of Phosphate Esters in Fresh and Aged Slices of Potato Tuber
      Tissue.

PMID- 16655838
TI  - Preparation and Properties of Sweet Potato Mitochondria.

PMID- 16655839
TI  - Response of Plants to Air Pollutants. I. Effects of Ozone on Tobacco Plants
      Preconditioned by Light and Temperature.

PMID- 16655840
TI  - Translocation of Calcium. Exchange versus Mass Flow.

PMID- 16655842
TI  - Auxin Oxidase and Growth Control in Tissue Cultures of Ephedra.

PMID- 16655843
TI  - Introduction of Mg into Chlorophylls a and b in vivo.

PMID- 16655844
TI  - Investigations of the Role of Iron in Chlorophyll Metabolism I. Effect of Iron
      Deficiency on Chlorophyll and Heme Content and on the Activities of Certain
      Enzymes in Leaves.

PMID- 16655845
TI  - Investigations of the Role of Iron in Chlorophyll Metabolism. II. Effect of Iron
      Deficiency on Chlorophyll Synthesis.

PMID- 16655846
TI  - Estimation of Nicotinamide Nucleotide Coenzymes in Etiolated Maize Seedlings.

PMID- 16655847
TI  - Effects of Light and Darkness on Biosynthesis of Carotenoid Pigments in Wheat
      Seedlings.

PMID- 16655848
TI  - Endogenous Growth Regulation in Carpophores of Agaricus bisporus.

PMID- 16655849
TI  - Kinetic Studies of Regreening of Iron-deficient Soybeans.

PMID- 16655850
TI  - Comparative Effects of 2,4-Dichlorophenoxyacetic Acid on Nitrate Metabolism in
      Corn and Cucumber.

PMID- 16655851
TI  - Further Studies on the Photochemical Production of Reduced Triphosphopyridine
      Nucleotide and Adenosine Triphosphate by Fragmented Spinach Chloroplasts.

PMID- 16655852
TI  - Malonic Acid Biosynthesis in Bush Bean Roots. I. Evidence for Oxaloacetate as
      Immediate Precursor.

PMID- 16655853
TI  - Malonic Acid Biosynthesis in Bush Bean Roots. II. Purification and Properties of
      Enzyme Catalyzing Oxidative Decarboxylation of Oxaloacetate.

PMID- 16655854
TI  - Effect of Light Quality on the Rhythmic Flowering Response of Biloxi Soybean.

PMID- 16655855
TI  - Resetting the Biological Clock in Gonyaulax with Ultraviolet Light.

PMID- 16655856
TI  - Effect of Chemical Closure of Stomata on Transpiration in Varied Soil and
      Atmospheric Environments.

PMID- 16655857
TI  - Effect of Soil Moisture and Phenylmercuric Acetate upon Stomatal Aperture,
      Transpiration, and Photosynthesis.

PMID- 16655858
TI  - Fat Utilization in Germinating Douglas Fir Seed.

PMID- 16655859
TI  - Paper Chromatography Method for Identification of Ethylene.

PMID- 16655860
TI  - Interaction of Growth-retarding Compounds and Gibberellin on Indoleacetic Acid
      Oxidase and Peroxidase of Cucumber Seedlings.

PMID- 16655861
TI  - The Occurrence of Auxin-induced Pectin Methylation in Plant Tissues.

PMID- 16655862
TI  - Metabolism of Indoleacetic Acid in Rust Diseases. I. Factors Influencing Rates of
      Decarboxylation.

PMID- 16655864
TI  - Metabolism of Indoleacetic Acid in Rust Diseases. II. Metabolites of Carboxyl
      labeled Indoleacetic Acid in Tissues.

PMID- 16655865
TI  - Emerson Enhancement Effect in Chloroplast Reactions.

PMID- 16655866
TI  - Uptake and Transport of Radiochloride and Tritiated Water by Various Zones of
      Onion Roots of Different Chloride Status.

PMID- 16655867
TI  - Chloride Uptake and Transport of Different Salt Status.

PMID- 16655868
TI  - Participation of Sulfhydryl Groups in Fatty Acid Synthesis by Chloroplast
      Preparations.

PMID- 16655869
TI  - Effects of Ethylene on Cantaloupe Fruits Harvested at Various Ages.

PMID- 16655870
TI  - Effects of Wounding on Respiration and Ethylene Production by Cantaloupe Fruit
      Tissue.

PMID- 16655871
TI  - News & Notes.

PMID- 16655872
TI  - Effects of Defoliation, Deradication, and Darkening the Blade upon Translocation
      of C in Sugarcane.

PMID- 16655873
TI  - Paper Chromatographic Study of Diffusible Auxin.

PMID- 16655874
TI  - Penetration of Ions through Isolated Cuticles.

PMID- 16655875
TI  - Light-Dependent Conversions of Endogenous alpha-Tocopherylquinone and
      Plastoquinone-D in Spinacia Oleracea Chloroplasts.

PMID- 16655876
TI  - The Requirement for Organic Nitrogen in Zea mays Embryos.

PMID- 16655877
TI  - Chlorophyllase and Formation of an Atypical Chlorophyllide in Marine Algae.

PMID- 16655878
TI  - Effect of Light on Sodium Influx, Membrane Potential, and Protoplasmic Streaming
      in Nitella.

PMID- 16655879
TI  - Acetolactate and Acetoin Synthesis in Ripening Peas.

PMID- 16655881
TI  - Spectrophotometric Method for Determination of Lipoxidase Activity.

PMID- 16655880
TI  - Exocellular Enzymes of Corn Roots.

PMID- 16655882
TI  - Chemotropic Response of the Pollen of Antirrhinum majus to Calcium.

PMID- 16655883
TI  - Absorption of Sugars by Plant Tissues.

PMID- 16655884
TI  - Modification and Use of an Electric Hygrometer for Estimating Relative Stomatal
      Apertures.

PMID- 16655885
TI  - Use of Pectic Enzymes in a Study of the Nature of Intercellular Cement of Tobacco
      Leaf Cells.

PMID- 16655886
TI  - Beta Ray Gauging Technique for Measuring Leaf Water Content Changes and Moisture
      Status of Plants.

PMID- 16655887
TI  - Uptake of Indole-3-acetic Acid and Indole-3-acetonitrile by Avena Coleoptile
      Sections.

PMID- 16655888
TI  - Enzymic Decarboxylation of Oxalate by Extracts of Plant Tissue.

PMID- 16655889
TI  - Aspects of Nucleic Acid Composition in Gossypium.

PMID- 16655890
TI  - Movement of Auxin in Coleoptiles of Zea mays L. during Geotropic Stimulation.

PMID- 16655891
TI  - Acids in Storage Tissues. Effects of Salts and Aging.

PMID- 16655892
TI  - Cell-free Hydrogenase from Chlamydomonas.

PMID- 16655893
TI  - Studies of Sulfate Utilization by Algae. II. Further Identification of Reduced
      Compounds Formed from Sulfate by Chlorella.

PMID- 16655894
TI  - Direct Evidence for Translocation of Sucrose in Sugarcane Leaves and Stems.

PMID- 16655895
TI  - Relationship of Solute Leakage to Solution Tonicity in Fruits and Other Plant
      Tissues.

PMID- 16655896
TI  - Effect of External K, NH(4), Na, Ca, Mg, and H Ions on the Cell Transmembrane
      Electropotential of Avena Coleoptile.

PMID- 16655897
TI  - Hadacidin, a New Plant-Growth Inhibitor Produced by Fermentation.

PMID- 16655898
TI  - Photosynthesis in Climatic Races of Mimulus. I. Effect of Light Intensity and
      Temperature on Rate.

PMID- 16655899
TI  - Simultaneous Studies of Transpiration Rate and Sap Velocity in Trees.

PMID- 16655900
TI  - Effect of Different Water Pretreatments on Potential Transpiration.

PMID- 16655901
TI  - Studies of Chloroplast Development in Euglena. V. Pigment Biosynthesis,
      Photosynthetic Oxygen Evolution and Carbon Dioxide Fixation during Chloroplast
      Development.

PMID- 16655902
TI  - Studies of Chloroplast Development in Euglena. VI. Light Intensity as a
      Controlling Factor in Development.

PMID- 16655903
TI  - Studies of Chloroplast Development in Euglena. VII. Fine Structure of the
      Developing Plastid.

PMID- 16655904
TI  - Water Uptake and Heat Evolution by Germinating Cotton Seed.

PMID- 16655905
TI  - Biosynthesis of Ricinine in Excised Roots of Ricinus communis.

PMID- 16655906
TI  - Dual Action of White Light in the Photocontrol of Germination of Oryzopsis
      miliacea.

PMID- 16655907
TI  - Influence of the Counter-ion on the Absorption Isotherm for Chloride at Low
      Temperature.

PMID- 16655908
TI  - Relationship between the Physical Nature of Mitochondrial Membranes and Chilling
      Sensitivity in Plants.

PMID- 16655909
TI  - Time-course Study of Translocation of Products of Photosynthesis in Soybean
      Plants.

PMID- 16655910
TI  - Absorption of Cations by Roots. Effects of Hydrogen Ions and Essential Role of
      Calcium.

PMID- 16655911
TI  - Photosynthetic Phosphorylation in the Presence of Spinach Phosphodoxin.

PMID- 16655912
TI  - Test of the Intermediary Role of Nicotine-1'-Oxide in Conversion of Nicotine to
      Nornicotine.

PMID- 16655913
TI  - Physiological Effects of Gibberellic Acid. VI. Other Gibberellins in Three Test
      Systems.

PMID- 16655914
TI  - Metabolism of Threo-D(s)-Isocitric Acid in Detached Leaves of Bryophyllum
      calycinum.

PMID- 16655915
TI  - CHARLES ALBERT SHULL MEMORIAL ISSUE: Charles A. Shull 1879-1962.

PMID- 16655916
TI  - Interaction between Kinetin and Light on Germination of Grand Rapids Lettuce
      Seeds.

PMID- 16655917
TI  - Hydrogen Metabolism in Higher Plants.

PMID- 16655918
TI  - Chemical Factors Affecting Anthocyanin Formation and Morphogenesis in Cultured
      Hypocotyl Segments of Impatiens balsamina.

PMID- 16655919
TI  - Metabolic Processes in Cytoplasmic Particles of the Avocado Fruit. VI. Controlled
      Oxidations and Coupled Phosphorylations.

PMID- 16655920
TI  - Pathways of Respiration in Plant Tumors.

PMID- 16655921
TI  - Effect of Light Quality on Growth and Free Indoleacetic Acid Content in Phaseolus
      vulgaris.

PMID- 16655922
TI  - Biosynthesis of Prunasin, the Cyanogenic Glucoside of Peach.

PMID- 16655923
TI  - Kinetin and Gibberellin Actions on Abscission Processes.

PMID- 16655924
TI  - Ion Absorption by Shoot Tissue: Technique and First Findings with Excised Leaf
      Tissue of Corn.

PMID- 16655925
TI  - Transport and Distribution of Auxin during Tropistic Response. II. The Lateral
      Migration of Auxin in Phototropism of Coleoptiles.

PMID- 16655926
TI  - Comparison of Lignin-like Products Found Naturally or Induced in Tissues of
      Phleum, Elodea, and Coleus, and in a Paper Perioxidase System.

PMID- 16655927
TI  - Enhancement by Auxin of Ribonucleic Acid Synthesis in Excised Soybean Hypocotyl
      Tissue.

PMID- 16655928
TI  - Ribonucleic Acid and Protein Synthesis as Essential Processes for Cell
      Elongation.

PMID- 16655929
TI  - Enzymic Mechanism of Starch Synthesis in Ripening Rice Grains.

PMID- 16655930
TI  - Studies on Water Regime and Nitrogen Metabolism of Citrus Seedlings Grown under
      Water Stress.

PMID- 16655931
TI  - Anion Absorption by Baker's Yeast.

PMID- 16655932
TI  - The Relation of Glucose Absorption to Respiration in Potato Slices.

PMID- 16655933
TI  - Ascorbic Acid Oxidase in Cell Growth.

PMID- 16655934
TI  - Effects of the Growth Retardant CCC on Floral Initiation and Growth in Pharbitis
      nil.

PMID- 16655935
TI  - Mechanism of Protection by Nonpenetrating and Nontoxic Solutes against Freezing
      Injury to Plant Cells.

PMID- 16655936
TI  - Gibberellic Acid Controlled Synthesis of alpha-Amylase in Barley Endosperm.

PMID- 16655937
TI  - Enzymic Assimilation of Nitrate in Tomato Plants. I. Reduction of Nitrate to
      Nitrite.

PMID- 16655938
TI  - Enzymic Assimilation of Nitrate in Tomato Plants. II. Reduction of Nitrite to
      Ammonia.

PMID- 16655939
TI  - The Glyoxylate Cycle in Maize Scutellum.

PMID- 16655940
TI  - Gibberellins and Light Inhibition of Stem Growth in Peas.

PMID- 16655941
TI  - The Appearance of Neoxanthin during the Regreening of Dark-grown Euglena.

PMID- 16655942
TI  - Function of Bean Roots and Stems in Sodium Retention.

PMID- 16655943
TI  - Ion Uptake by Soybean Root Tissue Depleted of Calcium by
      Ethylenediaminetetraacetic Acid.

PMID- 16655944
TI  - Sugar Gradients and Translocation of Sucrose in Detached Blades of Sugarcane.

PMID- 16655945
TI  - Further Studies on the Activation of Acetic Thiokinase by Magnesium and Univalent
      Cations.

PMID- 16655946
TI  - Influences of Stock and Scion on Alkaloid Synthesis and Transformation.

PMID- 16655947
TI  - Alteration of Oxidative Enzymes in Potato Tuber Tissue by Infection with
      Phytophthora infestans.

PMID- 16655948
TI  - The Kinetics of Chloride Accumulation and Transport in Exuding Roots.

PMID- 16655949
TI  - Effect of Water Movement on Ion Movement into the Xylem of Tomato Roots.

PMID- 16655950
TI  - Effects of Nonionic Surfactants on Root Growth and Cation Uptake.

PMID- 16655952
TI  - Photooxidation of Cytochromes c, f, and Plastocyanin by Detergent Treated
      Chloroplasts.

PMID- 16655953
TI  - ATP-Induced Inhibition of Potato Browning. Effect of Ascorbic Acid Oxidase and of
      Reducing Substances.

PMID- 16655954
TI  - Effects of Light and Darkness on Gaseous Exchange of Bean Leaves.

PMID- 16655955
TI  - Purine-Like Substances from Coconut Endosperm and Their Effect on Senescence in
      Excised Cereal Leaves.

PMID- 16655956
TI  - Influence of Foliar Leaching on Root Uptake and Translocation of Calcium-45 to
      the Stems and Foliage of Phaseolus vulgaris.

PMID- 16655957
TI  - Repression of Tissue Culture Growth by Visible and Near Visible Radiation.

PMID- 16655958
TI  - Relationship between Cell Permeability and Respiration in Ripening Banana Fruit
      Tissue.

PMID- 16655959
TI  - Proteins and Plant Cell Walls. Proline to Hydroxyproline in Tobacco Suspension
      Cultures.

PMID- 16655960
TI  - Lipid Transformations in Plastids of Bean Leaves and Pepper Fruits.

PMID- 16655961
TI  - Effects of Moisture Stress on Acid-Soluble Phosphorus Compounds in Trifolium
      subterraneum.

PMID- 16655962
TI  - Influence of Elevated Shoot and Root Temperature on Nitrogen Fixation.

PMID- 16655964
TI  - The Effect of Low Temperature on Ascent of Sap in Trees.

PMID- 16655963
TI  - Response of Plants to Air Pollutants. III. A Relation between Ascorbic Acid
      Levels and Ozone Susceptibility of Light-Preconditioned Tobacco Plants.

PMID- 16655965
TI  - Modification of Plant Transpiration Rate with Chemicals.

PMID- 16655966
TI  - Effect of Chloramphenicol on Light-Dependent Synthesis of Proteins and Enzymes of
      Leaves and Chloroplasts of Phaseolus vulgaris.

PMID- 16655967
TI  - Active Transport of Choline Sulfate by Barley Roots.

PMID- 16655968
TI  - Characterization of Leachate from Plant Foliage.

PMID- 16655969
TI  - Kinetics of Rb Absorption by Excised Barley Roots under Changing Rb
      Concentrations. II. An Interpretation of Kinetic Data.

PMID- 16655970
TI  - Isolation of Plastoquinones C and D from Spinach Chloroplasts.

PMID- 16655971
TI  - Interrelationship of Iron and Manganese Supply in Growth, Chlorophyll, and Iron
      Porphyrin Enzymes in Barley Plants.

PMID- 16655972
TI  - Phosphorus Tolerance and Sensitivity of Soybeans as Related to Uptake and
      Translocation.

PMID- 16655973
TI  - Photosynthesis in Healthy and Rust-Affected Plants.

PMID- 16655974
TI  - Enhancement of the Photosynthesis of Chlorella pyrenoidosa as a Function of Far
      Red and Short-Wave Illuminations.

PMID- 16655975
TI  - Organic Acids in the Ripening Banana Fruit.

PMID- 16655976
TI  - Flavonoid Complexes in Pisum sativum. II. Effects of Red and Far-Red Light on
      Biosynthesis of Kaempferol Complexes and on Growth in Etiolated Plumules.

PMID- 16655977
TI  - Isolation and Distribution of Phosphoglycolate Phosphatase.

PMID- 16655978
TI  - Ferricyanide-Mediated Transport of Chloride by Anaerobic Corn Roots.

PMID- 16655979
TI  - The Onset of Tricarboxylic Acid Cycle Activity with Aging in Potato Slices.

PMID- 16655980
TI  - Translocation of Photosynthetically Assimilated C in Straight-Necked Squash.

PMID- 16655981
TI  - Physiological Effects of Gibberellic Acid. VII. Electron Microscopy of Barley
      Aleurone Cells.

PMID- 16655982
TI  - Carotenoids of Wild Type and Mutant Strains of the Green Aiga, Chlamydomonas
      reinhardi.

PMID- 16655983
TI  - Determinations of the Heat Transfer Coefficient of a Leaf.

PMID- 16655984
TI  - Effects of Certain Growth Substances on the Growth and Morphogenesis of Immature
      Embryos of Capsella in Culture.

PMID- 16655985
TI  - Oxidation of Externally Added NADH by Isolated Corn Root Mitochondria.

PMID- 16655987
TI  - Freeze-Drying Pine Pollen.

PMID- 16655988
TI  - Effects of Indoleacetic Acid and Kinetin on Activities of Enzymes of the Hexose
      Monophosphate Shunt in Tissue Cultures of Nicotiana.

PMID- 16655989
TI  - Loss of Adenosine Triphosphate Synthesis Caused by Freezing and Its Relationship
      to Frost Hardiness Problems.

PMID- 16655990
TI  - Influence of Cobalt on Leaf Expansion and Oxidative Phosphorylation.

PMID- 16655991
TI  - Biosynthesis of the Methoxylated Carotenoids in Rhodospirillum rubrum.

PMID- 16655992
TI  - Studies on the Relationship between Ribonucleic Acid Content and the Rate of
      Growth of Corn Roots.

PMID- 16655993
TI  - Metabolic Changes Associated with the Germination of Corn. I. Changes in Weight
      and Metabolites and their Redistribution in the Embryo Axis, Scutellum, and
      Endosperm.

PMID- 16655994
TI  - Distribution of Indoleacetic Acid Oxidase and Inhibitors in Light-Grown Cotton.

PMID- 16655995
TI  - Photosynthesis in Climatic Races of Mimulus. II. Effect of Time and CO(2)
      Concentration on Rate.

PMID- 16655996
TI  - Ozone Effects on Cell Wall Metabolism of Avena Coleoptile Sections.

PMID- 16655997
TI  - Analysis of Germination Processes of Lettuce Seed by Means of Temperature and
      Anaerobiosis.

PMID- 16655998
TI  - Dormancy Associated with Repression of Genetic Activity.

PMID- 16655999
TI  - C Amino Acid Incorporation by Spinach Chloroplast Preparations.

PMID- 16656000
TI  - Light-Induced Trans to Cis Conversion of beta-d-Glucosyl o-Hydroxycinnamic Acid
      in Melilotus alba Leaves.

PMID- 16656001
TI  - Investigations on the Occurrence and Biosynthesis of Indolepyruvic Acid in Plant
      Tissues and Bacteria.

PMID- 16656002
TI  - Effects of Aging and Temperature on Respiratory Metabolism of Green Leaves.

PMID- 16656003
TI  - Steric Specificity in Synthesis of Heptuloses by Plants.

PMID- 16656004
TI  - Interaction of Nucleotides with Auxins in Growth of Pea Stem Segments.

PMID- 16656005
TI  - Ribonuclease Levels in the Mesocotyl Tissue of Zea mays as a Function of 2,4
      Dichlorophenoxyacetic Acid Application.

PMID- 16656006
TI  - Flash Spectroscopy of Porphyridium.

PMID- 16656007
TI  - Conditions Determining Effects of Far-Red and Red Irradiations on Flowering
      Response of Pharbitis nil.

PMID- 16656008
TI  - Interaction of Growth Substances in Growth and Organ Initiation in the Embryos of
      Capsella.

PMID- 16656010
TI  - Dividing Cells as the Prerequisite for Vernalization.

PMID- 16656009
TI  - Factors Influencing Dormancy of Peanut Seeds.

PMID- 16656011
TI  - Preparation of Indole Extracts from Plants for Gas Chromatography and
      Spectrophotofluorometry.

PMID- 16656012
TI  - Callose Formation and Subsequent Disappearance: Studies in Ultrasound
      Stimulation.

PMID- 16656013
TI  - Photoperiodic Flowering Response of Biloxi Soybean in 72-Hour Cycles.

PMID- 16656014
TI  - The Role of Glycolic Acid Metabolism in Opening of Leaf Stomata.

PMID- 16656015
TI  - Control by Iron of Chlorophyll Formation and Growth in Euglena gracilis.

PMID- 16656016
TI  - Physiological Aspects of Parasitism in Mistletoes (Arceuthobium and
      Phoradendron). II. The Photosynthetic Capacity of Mistletoe.

PMID- 16656017
TI  - The Occurrence of and Effect of Cyanide on Respiratory Drift in the Developing
      Tung Nut.

PMID- 16656018
TI  - Adenosine Triphosphatase Activity of Cauliflower Mitochondria.

PMID- 16656019
TI  - Effect of Temperature and Preconditioning on Photoperiodic Response of Pharbitis
      nil.

PMID- 16656020
TI  - Alkaloids and Plant Metabolism. VII. The Kinetin-Produced Elevation in Tyramine
      Methylpherase Levels.

PMID- 16656021
TI  - External Effect of Combined Nitrogen on Nodulation.

PMID- 16656022
TI  - Reversible Changes in the Hydraulic Permeability of Plant Cell Membranes.

PMID- 16656023
TI  - A Differential Psychrometer for Continuous Measurements of Transpiration.

PMID- 16656024
TI  - Cation, Organic Acid, and pH Relationships in Peel Tissue of Apple Fruits
      Affected with Jonathan Spot.

PMID- 16656026
TI  - Influence of Environment on Metabolism of Organic Acids and Carbohydrates in
      Vitis Vinifera. I. Temperature.

PMID- 16656027
TI  - Lipolysis and the Free Fatty Acid Pool in Seedlings.

PMID- 16656028
TI  - The Effect of Dual Perturbations on the Rhythmic Flowering Response of Biloxi
      Soybean.

PMID- 16656029
TI  - Regulation of Photosynthesis in Chlamydomonas reinhardi.

PMID- 16656030
TI  - The Relation of Oxygen Evolution to Chlorophyll and Protein Synthesis in a Mutant
      Strain of Chlamydomonas reinhardi.

PMID- 16656031
TI  - Studies on the Mode of Action of Malformin: Inhibition of Malformin.

PMID- 16656032
TI  - Anthocyanin Formation in Excised Segments of Buckwheat-Seedling Hypocotyls.

PMID- 16656033
TI  - Synthesis of Extracellular Polysaccharide by Suspensions of Acer Pseudoplatanus
      Cells.

PMID- 16656034
TI  - Comparison of the Uptake of P and K by Intact Alfalfa and Oat Roots.

PMID- 16656035
TI  - Effects of Cotyledon Excision on the Flowering of Five Varieties of Pisum
      sativum.

PMID- 16656036
TI  - Oxidative Enzyme and Protein Changes in Outgrowth Induced on Carrot Phloem by
      Agrobacterium tumefaciens.

PMID- 16656037
TI  - An Extra-Mitochondrial Enzyme System from Peanuts Catalyzing the beta-Oxidation
      of Fatty Acids.

PMID- 16656038
TI  - Enhancement in the Blue-Green Alga, Anacystis nidulans.

PMID- 16656039
TI  - Effect of Ammonium and Nitrate Nutrition on Protein Level and Exudate
      Composition.

PMID- 16656040
TI  - Dependence upon Wavelength of Stomatal Movement in Epidermal Tissue of Senecio
      odoris.

PMID- 16656041
TI  - Effect of Nucleotides on Enzymic Browning in Potato Slices.

PMID- 16656042
TI  - Extraction of Total Available Carbohydrates from Grass and Legume Tissue.

PMID- 16656043
TI  - Regulation of Ethylene Evolution and Leaf Abscission by Auxin.

PMID- 16656044
TI  - Metabolism of the Methyl Group of Nicotine in Nicotiana rustica.

PMID- 16656045
TI  - Stachyose Translocation in Plants.

PMID- 16656046
TI  - Ion Binding by Surfaces of Isolated Cuticular Membranes.

PMID- 16656047
TI  - Auxin Transport in the Physiology of Fruit Development.

PMID- 16656048
TI  - The Reversible Inhibition by Red and Far-Red Light of Auxin-Induced Lateral Root
      Initiation in Isolated Pea Roots.

PMID- 16656049
TI  - Ion Absorption by Shoot Tissue: Kinetics of Potassium and Rubidium Absorption by
      Corn Leaf Tissue.

PMID- 16656050
TI  - Physiological Aspects of Parasitism in Mistletoes (Arceuthobium and
      Phoradendron). I. The Carbohydrate Nutrition of Mistletoe.

PMID- 16656051
TI  - Calcium Accumulation by Maize Mitochondria.

PMID- 16656052
TI  - Photomorphogenic Responses of Dodder Seedlings.

PMID- 16656053
TI  - Auxin Transport in Flowering and Vegetative Shoots of Coleus blumei Benth.

PMID- 16656054
TI  - Translocation of C Metabolites in the Phloem of the Bean Plant.

PMID- 16656055
TI  - Dark Transformations of Phytochrome in vivo. II.

PMID- 16656056
TI  - Changes in Calcium Levels in Cell Walls during Elongation of Oat Coleoptile
      Sections.

PMID- 16656057
TI  - Expansion of Bean Leaves and its Suppression by Salinity.

PMID- 16656058
TI  - Comparison of Mitochondria from Tomato Fruits at Various Stages of Ripeness.

PMID- 16656059
TI  - Penetration of Organic Compounds Through Isolated Cuticular Membranes with
      Special Reference to C Urea.

PMID- 16656060
TI  - Auxin Transport in Geotropic Curvatures of a Branched Plant.

PMID- 16656061
TI  - Formic Acid Activation in Plants. I. Purification, Properties and Distribution of
      Formyltetrahydrofolate Synthetase.

PMID- 16656062
TI  - Formic Acid Activation in Plants. II. Activation of Formyltetrahydrofolate
      Synthetase by Magnesium, Potassium, and Other Univalent Cations.

PMID- 16656064
TI  - Red Light and the Geotropic Response of the Avena Coleoptile.

PMID- 16656065
TI  - Evidence for Translocation of Iron in Plants.

PMID- 16656066
TI  - Catabolism of Pyrimidines in Rape Seedlings.

PMID- 16656067
TI  - Conversion of Nicotine to Nornicotine in Grafts between Cherry-red Tobacco and
      Related Materials.

PMID- 16656068
TI  - Relationship Between Red Light Mediated Glyceraldehyde-3-Phosphate Dehydrogenase
      Formation and Light Dependent Development of Photosynthesis.

PMID- 16656069
TI  - Oxygen Uptake and Evolution Following Monochromatic Flashes in Ulva and an Action
      Spectrum for System I.

PMID- 16656070
TI  - The Effect of Temperature upon Translocation of C in Sugarcane.

PMID- 16656071
TI  - Natural Variations in the Physiological Characteristics of Growing Chlorella
      Cultures.

PMID- 16656072
TI  - The Morphogenetic Effect of Oxygen on Roots.

PMID- 16656073
TI  - Light and Dark CO(2) Fixation by Spinach Leaf Systems.

PMID- 16656074
TI  - Changes in Abscission Processes with Aging.

PMID- 16656075
TI  - Carbon Dioxide Fixation in Sugarcane Leaves.

PMID- 16656076
TI  - Ion Absorption and Retention by Chlorella pyrenoidosa. I. Absorption of
      Potassium.

PMID- 16656077
TI  - Further Studies Concerning Stomatal Diffusion.

PMID- 16656078
TI  - Effects of Osmotic Water Stress on Metabolic Rates of Cotton Plants with Open
      Stomata.

PMID- 16656079
TI  - Comparative Studies of the Hill Activity of Differentially Centrifuged
      Chloroplast Fractions.

PMID- 16656080
TI  - Biochemical Studies of Bud Dormancy in Tanweed.

PMID- 16656081
TI  - Bioassay of Floral Stimulus in Xanthium.

PMID- 16656082
TI  - Initiation of Floral Primordia in Cestrum diurnum and Cestrum nocturnum in
      Response to Various Photoperiodic Patterns.

PMID- 16656083
TI  - Some Effects of Photoperiod on the Biosynthesis of Phenylpropane Derivatives in
      Xanthium.

PMID- 16656084
TI  - Evidence for Conformational Changes in Euglena Chloroplasts.

PMID- 16656085
TI  - Effects of Gibberellic Acid on Utilization of Auxin Precursors by Apical Segments
      of the Avena Coleoptile.

PMID- 16656086
TI  - Carbohydrate and Protein Content of Boron-Deficient Tomato Root Tips in Relation
      to Anatomy and Growth.

PMID- 16656087
TI  - Transient Effects of Indoleacetic Acid on the Absorption and Utilization of
      Radioactive Acetate by Pea Stem Slices.

PMID- 16656088
TI  - Determination of Relative Auxin Content in Hermaphrodite and Andromonoecious
      Cucumis sativus L.

PMID- 16656089
TI  - A Comparison of Methods for the Removal of Cobalt and Vanadium from Salts Used in
      Plant Nutritional Studies.

PMID- 16656090
TI  - Metabolism of Glucose-C by Anabaena cylindrica.

PMID- 16656091
TI  - Effects of d and l Amino Acids on Foliar Abscission.

PMID- 16656092
TI  - Direct and Indirect Effects of Auxin on Cell Wall Synthesis in Oat Coleoptile
      Tissue.

PMID- 16656093
TI  - The Effect of Auxin on Synthesis of Oat Coleoptile Cell Wall Constituents.

PMID- 16656094
TI  - Relation between Effects of Auxin on Cell Wall Synthesis and Cell Elongation.

PMID- 16656095
TI  - The Photooxidation of Uric Acid by Anacystis nidulans.

PMID- 16656096
TI  - d-Xylulokinase and d-Ribulokinase in Higher Plants.

PMID- 16656097
TI  - Movement of Tritiated Water in the Root System of Helianthus annuus in the
      Presence and Absence of Transpiration.

PMID- 16656098
TI  - Movement and Distribution of THO in Tissue Water and Vapor Transpired by Shoots
      of Helianthus and Nicotiana.

PMID- 16656099
TI  - Citric-acid Induced Loss of Rigidity in Potato Tuber Slices.

PMID- 16656100
TI  - Iron Stress as Related to the Iron and Citrate Occurring in Stem Exudate.

PMID- 16656101
TI  - The Metabolism of Indole-3-acetic Acid by Geranium Stem Callus Cultures.

PMID- 16656103
TI  - Effect of Gamma Radiation on Rate of Ethylene and Carbon Dioxide Evolution by
      Lemon Fruit.

PMID- 16656104
TI  - Ion Uptake by Cells Enzymically Isolated from Green Tobacco Leaves.

PMID- 16656105
TI  - Amino Acid Metabolism in Young Pea Seedlings.

PMID- 16656106
TI  - An Analytic Study of the w-3 Genetic Lesion in Zea mays L.

PMID- 16656107
TI  - Correlative Studies on Plant Growth and Metabolism. I. Changes in Protein and
      Soluble Nitrogen Accompanying Gibberellin-Induced Growth in Lettuce Seedlings.

PMID- 16656108
TI  - Isolation and Properties of Gibberellin-like Substances from Citrus Fruits.

PMID- 16656109
TI  - Rates of Photosynthesis in Attached and Detached Bean Leaves, and the Effect of
      Spraying with Indoleacetic Acid Solution.

PMID- 16656111
TI  - Sodium as an Essential Micronutrient Element for a Higher Plant (A triplex
      vesicaria).

PMID- 16656110
TI  - Relative Kinetics of Chlorogenic and Caffeic Acids During the Onset of Boron
      Deficiency in Sunflower.

PMID- 16656112
TI  - Partial Purification of a Cell-Division Factor from Peas.

PMID- 16656113
TI  - Frost Hardiness Studies on Cabbage Grown under Controlled Conditions.

PMID- 16656114
TI  - Conversion of Tryptophan to Indoleacetamide and Further Conversion to
      Indoleacetic Acid by Plant Preparations.

PMID- 16656115
TI  - Lettuce Seed Germination: Evidence for a Reversible Light-Induced Increase in
      Growth Potential and for Phytochrome Mediation of the Low Temperature Effect.

PMID- 16656116
TI  - Effect of Iron Supply on Growth, Chlorophyll, Tissue Iron and Activity of Certain
      Enzymes in Maize and Radish.

PMID- 16656117
TI  - Seasonal Changes in Citrus Auxin and 2 Auxin Antagonists as Related to Fruit
      Development.

PMID- 16656118
TI  - Influence of Light Regime on the Toxicity and Physiological Activity of
      Herbicides.

PMID- 16656119
TI  - Effects of Ca Upon Metabolic and Nonmetabolic Uptake of Na and Rb by Root
      Segments of Zea mays.

PMID- 16656120
TI  - Colony Formation by Isolated Convolvulus Cells Plated on Defined Media.

PMID- 16656121
TI  - Measuring Transpiration Resistance of Leaves.

PMID- 16656122
TI  - Effect of Light Quality on Elongation, Adventitious Root Production and the
      Relation of Cell Number and Cell Size to Bean Seedling Elongation.

PMID- 16656123
TI  - Effect of Light of Several Spectral Bands on the Metabolism of Radioactive IAA in
      Bean Seedlings.

PMID- 16656124
TI  - Studies on the Inhibitor Resistant Respiration of the Fungus Myrothecium
      verrucaria.

PMID- 16656125
TI  - Temperature Controlled Growth Rates and Ribonucleic Acid Characteristics in
      Mimosa. Epicotyl Tissue.

PMID- 16656126
TI  - Isolation, Yield, and Fatty Acid Composition of Intracellular Particles from
      Ripening Fruits.

PMID- 16656127
TI  - Activity of Mitochondrial Preparations Obtained from Faris Sweet Lemon Fruit.

PMID- 16656128
TI  - Effect of Light Quality, Light Intensity and Temperature on Pigment Accumulation
      in Barley Seedlings.

PMID- 16656129
TI  - Some Effects of Phosphon on Germination Induced by Red Radiation and Gibberellic
      Acid in Seeds of Verbascum thapsus.

PMID- 16656130
TI  - Inhibition of Chlorophyll Synthesis by High Concentrations of Carbon Dioxide.

PMID- 16656131
TI  - Nucleic Acid Metabolism in Peanut Cotyledons.

PMID- 16656133
TI  - IN MEMORIUM: David Powell Hackett.

PMID- 16656134
TI  - The Chemical Induction of Parthenocarpy in the Calimyrna Fig and its
      Physiological Significance.

PMID- 16656135
TI  - The Respiratory Pattern in the Tomato Fruit and its Alteration by Infiltration
      with Various Chemicals.

PMID- 16656136
TI  - Absorption of Chloride by Barley Roots: Kinetics and Selectivity.

PMID- 16656137
TI  - Absorption and Transport of Sodium and Potassium in Squash.

PMID- 16656138
TI  - Light-Dependent Ion Translocation in Spinach Chloroplasts.

PMID- 16656139
TI  - Accumulation of Calcium in Exudate of Individual Barley Roots.

PMID- 16656140
TI  - Ribonucleic Acid Content, Boron Deficiency Symptoms, and Elongation of Tomato
      Root Tips.

PMID- 16656141
TI  - Metabolic Changes Associated with the Germination of Corn. III. Effects of
      Gibberellic Acid on Endosperm Metabolism.

PMID- 16656142
TI  - Polarity of Transport of Benzyladenine, Adenine and Indole-3-acetic Acid in
      Petiole Segments of Phaseolus vulgaris.

PMID- 16656143
TI  - Composition of Volatiles in Allium as Related to Habitat, Stage of Growth, and
      Plant Part.

PMID- 16656144
TI  - Sucrose Translocation in the Sugar Beet.

PMID- 16656145
TI  - The Role of Light and Nitrate in the Induction of Nitrate Reductase in Radish
      Cotyledons and Maize Seedlings.

PMID- 16656146
TI  - Auxin Activity of Isatin and Oxindole-3-Acetic Acid.

PMID- 16656147
TI  - Physical Aspects of the Internal Water Relations of Plant Leaves.

PMID- 16656148
TI  - Radial Exchange of Labeled Water in Intact Maize Roots.

PMID- 16656149
TI  - Light and Translocation of C in Detached Blades of Sugarcane.

PMID- 16656150
TI  - Evapotranspiration of Pineapple in Hawaii.

PMID- 16656151
TI  - Selective and Preferential Translocation of C-Labeled Sugars in White Ash and
      Lilac.

PMID- 16656152
TI  - Oxidative and Phosphorylative Activities of Mitochondria Isolated from Pea Root
      Tissues.

PMID- 16656153
TI  - Malonate and Cyanide Insensitivity in Relation to Respiratory Compensation in
      Potato Slices.

PMID- 16656154
TI  - Respiration and Embryogenesis in Cotton.

PMID- 16656155
TI  - Relation of Seededness and Ringing to Gibberellin-like Activity in Berries of
      Vitis vinifera.

PMID- 16656158
TI  - Rapid Changes in Transpiration in Banana Leaves.

PMID- 16656157
TI  - Induction of Phenylalanine Deaminase by Light and its Relation to Chlorogenic
      Acid Synthesis in Potato Tuber Tissue.

PMID- 16656159
TI  - An Action Spectrum for Light Induced Sporulation in the Fungus Ascochyta pisi.

PMID- 16656160
TI  - Effect of Light on the Incorporation of Serine into the Carbohydrates of
      Chloroplasts and Nonchloroplast Fractions of Tobacco Leaves.

PMID- 16656161
TI  - Effect of Light and Dark on the Intracellular Fate of Photosynthetic Products.

PMID- 16656162
TI  - The Influence of Light, Oxygen and Temperature on the Herbicidal Properties of
      Paraquat.

PMID- 16656163
TI  - Changes in Composition during Development and Maturation of Maize Seeds.

PMID- 16656164
TI  - Factors Controlling the Synthesis of Natural and Induced Lignins in Phleum and
      Elodea.

PMID- 16656165
TI  - Studies on Red Light Interruption in Relation to Timing Mechanisms Involved in
      the Photoperiodic Response of Pharbitis nil.

PMID- 16656166
TI  - Effect of Double Red Light Interruptions on the Photoperiodic Response of
      Pharbitis nil.

PMID- 16656167
TI  - Effect of Far-Red Light and its Interaction with Red Light in the Photoperiodic
      Response of Pharbitis nil.

PMID- 16656168
TI  - Kinetic Studies on Pigment Systems Concerned with the Photoperiodic Response in
      Pharbitis nil.

PMID- 16656169
TI  - Quantitative Assay of Photoperiodic Floral Inhibition and Stimulation in Biloxi
      Soybean.

PMID- 16656170
TI  - Survival of Plant Tissue at Super-Low Temperature III. Relation between Effective
      Prefreezing Temperatures and the Degree of Front Hardiness.

PMID- 16656171
TI  - On Antheridial Metabolism in the Fern Species Onoclea sensibilis L.

PMID- 16656172
TI  - Calcium Activation of Orthophosphate Absorption by Barley Roots.

PMID- 16656173
TI  - Effects of Near Ultraviolet and Green Radiations on Plant Growth.

PMID- 16656174
TI  - Temperature Dependence of Photosynthesis of Bean Plants as Affected by
      Decenylsuccinic Acid.

PMID- 16656175
TI  - Effect of Phosphorylated Compounds and Inhibitors on CO(2) Fixation by Intact
      Spinach Chloroplasts.

PMID- 16656176
TI  - Rhizobial-Induced Chlorosis in Soybeans: Isolation, Production in Nodules, and
      Varietal Specificity of the Toxin.

PMID- 16656177
TI  - Production of the Soybean-Chlorosis Toxin by Rhizobium japonicum in Pure Culture.

PMID- 16656178
TI  - Distribution of Phytochrome in Etiolated Seedlings.

PMID- 16656179
TI  - Evaluation of Selected Parameters in a Sugar Beet Translocation System.

PMID- 16656180
TI  - Action of Gravity on Basipetal Transport of Auxin.

PMID- 16656181
TI  - Effect of Gravity Compensation on the Geotropic Sensitivity of Avena Seedlings.

PMID- 16656182
TI  - Auxin Transport and Geoelectric Potential in Corn Coleoptile Sections.

PMID- 16656184
TI  - Studies on the Isolation of Mitochondria from Potato Tuber Tissue.

PMID- 16656185
TI  - Respiratory Activity of the Mitochondrial Fractions Isolated from Healthy Potato
      Tubers and from Tuber Tissue Incubated after Cutting or Infection with
      Ceratocystis fimbriata.

PMID- 16656186
TI  - Effect of Light on the Tricarboxylic Acid Cycle in Scenedesmus.

PMID- 16656187
TI  - Action of Calcium on Corn Mitochondria.

PMID- 16656188
TI  - Nitrogen Fixation by Ceanothus.

PMID- 16656189
TI  - Distribution of C in Serine and Glycine after CO(2) Photosynthesis by Isolated
      Chloroplasts. Modification of Serine-C Degradation.

PMID- 16656190
TI  - Effect of Inhibitors and Uncouplers on the Separate Light and Dark Reactions in
      Photophosphorylation.

PMID- 16656191
TI  - Light-Dependent Volume Changes and Reactions in Chloroplasts. II. Action of
      Anions.

PMID- 16656192
TI  - Fractionation of Chlorophyll Forms from Euglena and Measurement of Light-Induced
      Absorbance Changes.

PMID- 16656193
TI  - Respiratory Chain of Colorless Algae I. Chlorophyta and Euglenophyta.

PMID- 16656194
TI  - Chloroplast Integrity and Biochemical Function.

PMID- 16656195
TI  - Physical Properties of Spinach Chloroplast Lamellar Proteins.

PMID- 16656196
TI  - Isolation of Phytoflavin, A Flavoprotein with Chloroplast Ferredoxin Activity.

PMID- 16656197
TI  - Ion Uptake and Phosphorylation in Mitochondria: Effect of Monovalent Ions.

PMID- 16656198
TI  - Utilization of Reserves in Germinating Phaseolus Seeds.

PMID- 16656199
TI  - Triosephosphate Isomerase of Pea Seeds.

PMID- 16656200
TI  - Effects of DCMU and Antimycin A on Photoassimilation of Glucose in Chlorella.

PMID- 16656201
TI  - Correlation between Photosynthetic Activity and Membrane Integrity in Isolated
      Pea Chloroplasts.

PMID- 16656202
TI  - On the Development of the Ribosomal System in the Endosperm of Germinating Castor
      Bean Seeds.

PMID- 16656203
TI  - Respiratory Metabolism in Detached Rhododendron Leaves.

PMID- 16656204
TI  - Radioactive Tracer Studies of the Metabolic Fates of Intracellularly Generated
      NADH and NADPH in Higher Plant Tissues.

PMID- 16656205
TI  - Kinetics of Cytochrome Oxidation in Skunk Cabbage Mitochondria.

PMID- 16656206
TI  - Control of Triosephosphate Dehydrogenase in Photosynthesis.

PMID- 16656207
TI  - Terminal Respiration of Vegetative Cells and Zygospores in Chlamydomonas
      reinhardi.

PMID- 16656208
TI  - Benzimidazole Effect in Chloroplasts of Wheat Leaves.

PMID- 16656209
TI  - Phosphate Metabolism and Induced Respiration in Washed Carrot Slices.

PMID- 16656210
TI  - Photochemical Activities of Spinach Chloroplasts Following Treatment with the
      Detergent Triton X-100.

PMID- 16656211
TI  - Influence of Growth Conditions on the Enhancement of Photophosphorylation by
      Carbon Dioxide.

PMID- 16656213
TI  - Glycolic Acid Oxidase in Castor Bean Endosperm.

PMID- 16656214
TI  - Calculation of Purity and Yields in the Purification of b-Type Cytochromes from
      Etiolated Seedlings of Phaseolus aureus.

PMID- 16656215
TI  - DAVID POWELL HACKETT MEMORIAL ISSUE: David Powell Hackett 1925-1965.

PMID- 16656216
TI  - Responses of Heterotrophic Cultures of Chlorella vulgaris Beyerinck to Darkness
      and Light. I. Pigment and pH Changes.
AB  - Glucose cultures of Chlorella vulgaris were grown in white light, in
      monochromatic light, and in darkness. Difference spectra showed that all
      wavelengths resulted in increased pigmentation over the dark controls.Cells
      irradiated with the 600 mmu beam showed a much higher absorption in the blue end
      of the spectrum with respect to the red end than is normally found in absorption
      spectra of white-light grown Chlorella cells.Dry weight comparisons between
      monochromatic light and dark controls showed the controls to be somewhat higher.
      This demonstrated that the monochromatic irradiation produced pigment synthesis
      but no increase in growth. Dark growth experiments suggested that cultures
      incubated in darkness on glucose excreted an acidic product.

PMID- 16656217
TI  - Day-night Differences in the Accumulation and Translocation of Ions by Tobacco
      Plants.
AB  - More K(42), Rb(86), and Br(82) was accumulated by intact tobacco plants and root
      systems from detopped plants during the night than during the day when studies
      for both periods were made in dark rooms controlled at 18 degrees . More,
      however, was translocated to shoots during the day than during the night in
      intact plants. This latter effect parallels the periodicity of exudation in root
      systems from detopped plants.

PMID- 16656218
TI  - Effect of chloral hydrate and acetaldehyde on mitochondrial preparations from
      sweet potato.
AB  - The inhibitory effects of chloral hydrate and acetaldehyde have been studied on
      oxidations performed by mitochondrial preparations of sweet potatoes (Ipomea
      batatas). With a variety of substrates, chloral acts very like amytal but only
      between a fifth and a tenth as effectively; it affects those reactions which
      would be expected to depend on the oxidation of intramitochondrial DPNH, more
      than the oxidation of succinate or of added DPNH. It also acts like amytal when
      oxygen is replaced by other electron accepting agents. It is more effective, for
      example, against the malate reduction of cytochrome c than against the malate
      reduction of 2:6-dichlorophenol-indophenol.Inhibitions producd by acetaldehyde
      are more complex. Some DPN-dependent oxidations, especially those of pyruvate and
      alpha-keto-glutarate, are strongly inhibited, while that of citrate is not.It is
      suggested that chloral affects the electron transport sequence of sweet potato
      mitochondria at a similar locus to amytal. Although the present work fails to
      provide unambiguous evidence that acetaldehyde acts in the same manner,
      experiments described in the literature have been interpreted in this way.

PMID- 16656219
TI  - Inheritance of Factors Affecting Floral Primordia Initiation in Cestrum; Hybrids
      of C. elegans and C. nocturnum.
AB  - Photoperiod patterns of hybrids of Cestrum elegans (Brongn.) Schlect., a day
      neutral plant, and C. nocturnum L., a long-short day and long day plant, were
      investigated. Plants of the F(1) generation, F(2) generation, and backcrosses to
      each parent were tested on short day, long day, continuous light, long-short day
      and short-long day for floral primordia initiation. The data recorded suggest 2
      independent genes or gene groups controlling floral primordia initiation in C.
      nocturnum, a single dominant gene that is activated by long-short day treatment
      and a recessive gene or genes responding to long day treatment. Further, these
      data suggest that the day neutral condition in C. elegans is the result of the
      series of independent genes or gene groups that respond to various photoperiods,
      the combination of these genes resulting in floral primordia initiation on all
      photoperiods.

PMID- 16656220
TI  - CO(2) Assimilation by Etiolated Hordeum vulgare Seedlings during the Onset of
      Photosynthesis.
AB  - The assimilation of CO(2) by etiolated Hordeum vulgare seedlings during an
      illumination period indicates a conversion of the organisms to autotrophy.After 1
      hour illumination, increases in the photo-assimilation of CO(2) are observed and
      the distribution of C(14) in the soluble fraction of the plants is predominantly
      in intermediates of the Calvin cycle.

PMID- 16656221
TI  - Pressure and flow relations in vascular bundles of the tomato plant.
AB  - In the tomato plant water flows through primary xylem in accordance with
      Poiseuille's law. This relation and the analogy between Poiseuille's and Ohm's
      law were employed to calculate rates of flow and differences in pressure within
      vascular bundles when transpiration rates from individual leaves were known. The
      resistance of vascular bundles to flow was calculated from a modification of
      Poiseuille's law and from measurements of vessels in all bundles. The rates of
      flow in all bundles were derived from a set of simultaneous linear equations of
      flow, written to correspond with the nature of the vascular network. Values of
      the difference in pressure associated with flow in bundles were derived from
      resistances and flow rates in individual bundles. These agreed substantially with
      values observed in a comparable plant.In large bundles, vessels occur in a
      frequency distribution that is approximately normal with respect either to the
      logarithms of their radii or to the fourth power of their radii. The largest
      vessels in a bundle transport most of the water when they are functioning.The
      tomato plant contains 2 types of vascular bundle. The large bundles of the stem
      form a network by joining above each node in combinations of 2 at a time. The
      small bundles of the stem and petiolar bundles are independent of other bundles
      from their origins at junctions to their termini. The small bundles offer high
      resistance to flow, whereas the resistance of large bundles is low. The average
      conductance of large bundles decreases from the base to the apex of the stem.
      That of small vascular bundles remains low and more or less constant throughout
      the plant.Only a small difference in pressure is required to maintain flow in
      large bundles. For lower leaves, the driving pressure required to move water to
      the base of a petiole is considerably less than that which moves water through
      petioles. The difference in pressure that maintains flow increases steadily for
      successively higher nodes. However, the pressure that drives flow to leaves is
      not always greater for higher leaves than for intermediate ones. For the plant
      examined, the highest leaves required a smaller amount of energy to move water
      from the ground than intermediate leaves did. This was also true of the power
      expended in moving water to individual leaves.In the large network bundles,
      significant cross transfer of flow occurs at junction points from one bundic to
      another. Because of the interconnections between large bundles. pressure and flow
      relations are apparently not greatly altered when localized dysfunction occurs in
      the vessels of large bundles. In small, independent bundles, a localized
      dysfunction in vessels produces a significant effect on pressure and flow
      relations.

PMID- 16656222
TI  - Correlation of alpha-Linolenate to Photosynthetic O(2) Production in Chlorella.
AB  - Photosynthetic oxygen evolution per milligram of chlorophyll in Chlorella
      vulgaris varies with the age of the culture. The rate of oxygen evolution is low
      in the starting cells, it rises to a maximum after 24 hours of growth and then
      declines to the initial low value after 72 to 90 hours. These changes in
      photosynthetic competence of chlorophyll in Chlorella are paralleled by changes
      in alpha-linolenate per milligram of chlorophyll. In general the magnitude of the
      photosynthetic competence of chlorophyll is directly proportional to the
      magnitude of the ratio of alpha-linolenate to chlorophyll, regardless of whether
      high ratios are due to high alpha-linolenates or low chlorophyll values. This
      relationship holds when the cultures are grown either under continuous or
      intermittent illumination.

PMID- 16656223
TI  - Rate of Glycolate Formation During Photosynthesis at High pH.
AB  - The products of C(14)O(2) fixation by Chlamydomonas and Chlorella were studied
      under conditions most favorable for glycolate synthesis. The highest percentage
      of the C(14) was incorporated into glycolate in the pH range of 8 to 9. After 1
      to 2 minutes as much as 40% of the C(14) was found in glycolate products and only
      a trace of C(14) was present as phosphoglycerate. Below pH 8 the rate of
      photosynthesis was much faster, but only a small percent of the C(14) was
      incorporated into glycolate in 1 or 2 minutes, while a high percent of the C(14)
      accumulated in phosphoglycerate. C(14) labeling of glycolate even at pH 8 or
      above did not occur at times shorter than 10 seconds. During the first seconds of
      photosynthesis, nearly all of the C(14) was found in phosphoglycerate and sugar
      phosphates. Thus glycolate appears to be formed after the phosphate esters of the
      photosynthetic carbon cycle.Washing Chlamydomonas with water 2 or 3 times
      resulted in the loss of most of their free phosphate. When a small aliquot of
      NaHC(14)O(3) was added to washed algae in the absence of this buffering capacity,
      the pH of the algal medium became 8 or above and much of the fixed C(14)
      accumulated in glycolate.

PMID- 16656224
TI  - Effect of aluminum on the uptake and metabolism of phosphorus by barley
      seedlings.
AB  - The uptake of P(32) and its incorporation into phosphorylated compounds was
      examined in the roots of barley seedlings which had been pretreated with
      aluminum.The rate at which phosphorus increased in Al-roots was greater than in
      controls, especially during the first 15 minutes of incubation. It was shown that
      the increased phosphorus in Al-roots was P(i) and that it was almost completely
      exchangeable. Similar increases over controls were found when root segments were
      incubated in phosphorus solutions containing 10(-3)m DNP and at low temperature.
      The increased P(i) in Al-roots did not result in an increase in the total amount
      of phosphorus incorporated into phosphorylated compounds.Aluminum treatment
      markedly decreased the incorporation of P(32) into sugar phosphates but increased
      the pool size of ATP and other nucleotide triphosphates present in the roots. The
      specific activities of P(32) in ATP in Al-roots and controls were similar
      indicating that the rates of ATP synthesis were similar in each case.Preliminary
      investigations showed that aluminum citrate inhibited both purified yeast
      hexokinase and phosphorylated sugar production by crude mitochondrial extracts
      from barley roots.The results suggest that there are 2 reactions between aluminum
      and phosphorus: 1) at the cell surface or in the free space which results in the
      fixation of phosphate by an adsorption-precipitation reaction; 2) within the
      cell, possibly within the mitochondria, which results in a marked decrease in the
      rate of sugar phosphorylation, probably effected by the inhibition of hexokinase.
      The evidence does not support the view that aluminum enhances phosphorus uptake
      or that the superficial reaction between aluminum and phosphate interferes with
      phosphorus transport.

PMID- 16656225
TI  - Transport of amino acids to the maize root.
AB  - When 5-mm maize root tips were excised and placed in an inorganic salts solution
      for 6 hours, there was a loss of alcohol-insoluble nitrogen. The levels of
      threonine, proline, valine, isoleucine, leucine, tyrosine, phenylalanine, and
      lysine in the alcohol soluble fraction were severely reduced, whereas those of
      glutamate, aspartate, ornithine, and alanine were scarcely affected. There was a
      4-fold increase in the level of gamma-aminobutyrate. Those amino acids whose
      synthesis appeared to be deficient in excised root tips also showed poor
      incorporation of acetate carbon. In addition, the results show that asparagine
      and the amino acids of the neutral and basic fraction were preferentially
      transported to the root tip region. The results therefore suggest that the
      synthesis of certain amino acids in the root tip region is restricted, and that
      this requirement for amino acids in the growing region could regulate the flow of
      amino acids to the root tip.

PMID- 16656226
TI  - The regulation of sugar uptake and accumulation in bean pod tissue.
AB  - The identity, localization and physiological significance of enzymes involved in
      sugar uptake and accumulation were determined for endocarp tissue of pods of
      Kentucky Wonder pole beans (Phaseolus vulgaris). An intracellular, alkaline
      invertase (pH optimum, 8) was assayed in extracted protein, as well as enzymes
      involved in sucrose synthesis, namely, uridinediphosphate (UDP-glucose
      pyrophosphorylase and UDP-glucose-fructose transglucosylase). Indirect evidence
      indicated the presence also of hexokinase, phosphohexoseisomerase and
      phosphoglucomutase. The data suggested that sucrose synthesis occurred in the
      cytoplasm, and that both sugar storage and an alkaline invertase occurred in the
      vacuole. The latter functions to hydrolyze accumulated sucrose. An outer space
      invertase (pH optimum, 4.0) was detected, but was variable in occurrence.
      Although its activity at the cell surface enhanced sucrose uptake, sucrose may be
      taken up unaltered.Over a wide range of concentrations of exogenous glucose the
      sucrose/reducing sugar ratio of accumulated sugars remained unchanged at about
      20. Synthesis of sucrose appears to be requisite to initial accumulation from
      glucose or fructose, as free hexoses do not increase at the apparent saturating
      concentration for uptake. Sucrose accumulation from exogenous hexose represents a
      steady-state value, in which sucrose is transported across the tonoplast into the
      vacuole at a rate equivalent to its rate of synthesis. Evidence indicates that
      this component of the accumulation process involves active transport of sucrose
      against a concentration gradient. The ratio of sucrose/reducing sugars in the
      accumulated sugars immediately after a period of uptake was inversely related to
      the level of inner space invertase. Within 16 hours after a period of
      accumulation, practically all of the sugar occurs as glucose and fructose.The
      absence of competition among hexoses and sucrose indicated that a common carrier
      was not involved in their uptake. From a series of studies on the kinetics of
      uptake of glucose and fructose, including competition studies, the effects of
      inhibitors, radioactive assay of accumulated sugars and the distribution of label
      in accumulated sucrose it appeared that rate limitation for glucose or fructose
      uptake resides in the sequence of reactions leading to sucrose synthesis, rather
      than in a process mediated by a carrier protein.

PMID- 16656227
TI  - Purification and partial characterization of a factor in cotton wax stimulating
      the germination of self-inhibited wheat stem rust uredospores.
AB  - Filter paper, nonabsorbent cotton, and cotton wax were found to be progressively
      richer sources of germination-stimulatory activity effective in counteracting the
      self-inhibition of Puccinia graminis var. tritici Erikss. and E. Henn
      uredospores. The major stimulatory component of cotton wax was purified and
      partially characterized. It was catalytically effective in stimulating
      germination and oxygen consumption of uredospores and appeared to be as active as
      pelargonaldehyde. Unlike most of the previously reported chemical stimulants,
      however, it was not active across an air gap.Although the active compound was not
      identified, both the ultraviolet spectrum and the nonionic and solubility
      properties of the active fractions were consistent with the infrared spectrum
      which indicated a relatively long-chained. alpha. beta unsaturated carbonyl
      compound such as a ketone or possibly an ester.The purification procedure
      involved deionization of ethanolic extracts from cotton or cotton wax on Dowex 50
      (H(+)) and Dowex 1 (OH(-)) columns followed by chromatography on neutral alumina
      using ethylene dichloride as the developing and eluting solvent.

PMID- 16656228
TI  - Effect of 4,6-Dinitro-o-sec-butylphenol on Phosphorus Accumulation and
      Incorporation in Tomato Leaf Disks.
AB  - The accumulation and incorporation of externally applied P(32) into ATP and the
      effect of 4,6-dinitro-o-sec-butylphenol (DNBP) on these processes was studied,
      using tomato (Lycopersicon esculentum Mill.) leaf disks.P(32) was, in most part,
      actively accumulated into leaf disks with time and was incorporated into ATP and
      other organic phosphates. DNBP inhibited both P(32) accumulation and ATP
      generation. The amount of inhibition increased with time of incubation.It is
      concluded that P(32) accumulation is related to ATP generation. Even though DNBP
      greatly inhibits phosphorus accumulation, there is little or no effect on its
      retention.DNBP has the ability to uncouple oxidative phosphorylation. Therefore,
      it is assumed that its inhibitory effect on phosphate accumulation and generation
      of high-energy phosphorus esters is related to its inhibition of oxidative
      phosphorylation.A method is described which appears to be satisfactory to
      determine the relative amounts of ATP and ADP in leaf disks labeled with P(32).

PMID- 16656229
TI  - Reduction in Turgor Pressure as a Result of Extremely Brief Exposure to CO(2).
AB  - CO(2) depresses water influx into sunflower hypocotyl segments of low water
      potential; by contrast, it stimulates flux into segments of high water potential.
      When segments of high potential were placed in a series of mannitol
      concentrations and allowed to achieve steady rates of water uptake, influx into
      CO(2)-treated tissue in a solution of 3 atm equalled that into control tissue in
      water. Reasons are given for deducing that a change in internal osmotic
      concentration (pi(i)) of the order of 40% would be necessary to account for this
      result on the basis of pi(i). Direct measurements (by cryoscopy and by the
      minimum volume method) detected no difference in the steady state value for pi(i)
      as between CO(2)-treated and control tissue. It was therefore concluded that
      CO(2) had caused some reduction in turgor pressure.Water uptake into tissue
      treated with CO(2) for only the first 2 minutes of a 30-minute period was equal
      to that into tissue treated continuously with CO(2), i.e. 3 times the control
      value. Ten seconds' CO(2) treatment produced a significant stimulation. When the
      cycles of treatment were repeated the samples receiving flashes of CO(2)
      maintained a rate of water uptake superior to that of the control, whereas influx
      into continuously treated tissue fell below the control value after 1 hour.CO(2)
      treatment applied in a moist air chamber stimulated subsequent water influx when
      the tissue was transferred to water. Fifteen seconds' treatment was sufficient to
      produce a marked effect. Even when a transition period of 30 minutes in the moist
      chamber was interposed between CO(2) treatment (5 minutes) and transfer to water,
      a stimulation was observed. The CO(2) effect could be achieved at zero degrees; 5
      minutes' treatment in the moist chamber at zero degrees, followed by a 15-minute
      transition period at the same temperature, substantially increased subsequent
      water uptake at 25 degrees .

PMID- 16656230
TI  - Effects of ethylene on auxin transport.
AB  - The effect of ethylene on the uptake, distribution and polar transport of C(14)
      from indole-3-acetic acid-2-C(14) and naphthalene acetic acid-1-C(14) in tissue
      sections was studied. Test species were cotton (Gossypium hirsutum, L.) and
      cowpea (Vigna sinensis, Endl.). Generally, incubation of tissue or intact plants
      with ethylene reduced the degree of polar auxin transport. Ethylene inhibited the
      movement of both auxins in stem tissue and IAA in petiole tissue of cotton. The
      effect of ethylene on auxin movement in cow-peas was more complex. Ethylene
      apparently inhibited transport in younger petiole and stem tissue, but stimulated
      the process to a small but significant degree in basal petiole segments.Ethylene,
      in some experiments, reduced C(14) (auxin) uptake. This reduction was
      consistently smaller than the inhibition of transport. Effects upon transport
      were observed when uptake was not different. Differences in uptake declined as
      the period of incubation with auxin was lengthened, but transport was inhibited
      for up to 23 hours.It is proposed that ethylene may, through its effect on
      transport, cause localized shortages and surpluses of auxin which in turn
      contribute to symptoms now associated with the response of sensitive species to
      ethylene.

PMID- 16656231
TI  - Isolation, Crystallization, and Partial Identification of Potato Factor II from
      Potato Tubers.
AB  - The isolation, crystallization, and partial identification of potato factor II, a
      stimulator from the chemically neutral fraction of potato extract, is described.
      The compound was originally found to stimulate elongation of dwarf peas grown
      under red light, a gibberellin bioassay. It melts between 137 degrees and 139
      degrees . In paper chromatography it migrates to R(F) 0.62 in isopropyl alcohol:
      ammonium hydroxide: H(2)O (10:1:1, v/v). Based on infrared and NMR data, it does
      not contain a lactone ring and possibly possesses an amide radical and an OH(-)
      group, as well as many methylene radicals. Potato factor II may be similar to
      certain of the fatty acid derivatives previously reported to stimulate growth of
      excised sections, but it is unique in that it stimulates growth of intact plants.
      This effect points to the need for completely separating neutral from acid
      gibberellin-like substances when the latter are assayed on dwarf peas.

PMID- 16656232
TI  - Hormonal Relations in the Phototropic Response: III. The Movement of C-labeled
      and Endogenous Indoleacetic Acid in Phototropically Stimulated Zea Coleoptiles.
AB  - The effect of phototropic stimulation of Zea coleoptile tips on the distribution
      of both endogenous indoleacetic acid (IAA) and applied C(14)-labeled IAA was
      determined. The tips rested on bisected agar blocks. More IAA was found in the
      blocks under the shaded side of the coleoptile tips than those under the
      irradiated side. However, no significant difference was observed between the
      total amounts of IAA, endogenous or labeled, in the irradiated and shaded sides
      of the experimental system. In addition, less endogenous auxin was found in the
      shaded tissues than in their irradiated counterparts. It is suggested that
      phototropism following unilateral irradiation with first positive radiant
      densities might be a consequence of lateral inequalities in the ability of the
      irradiated and shaded tissues to transport auxin basipetally.

PMID- 16656233
TI  - Metabolic transformation of mevalonic Acid by an enzyme system from peas.
AB  - En enzyme system has been found in peas which converts mevalonic acid to
      isoprenoid compounds. Among the intermediates in such conversion are mevalonic
      acid-5-phosphate and pyrophosphate, isopentenyl pyrophosphate and
      dimethylallylpyrophosphate. Among the products formed by the system are the
      pyrophosphates of geraniol, farnesol, nerolidol and higher isoprenoid alcohols.

PMID- 16656234
TI  - Responses of Heterotrophic Cultures of Chlorella vulgaris Beyerinck to Darkness
      and Light. II. Action Spectrum for and Mechanism of the Light Requirement for
      Heterotrophic Growth.
AB  - Chlorella vulgaris Beyerinck (Emerson's strain), fails to grow in the dark even
      when sugars are provided. This phenomenon was clearly demonstrated in the alga,
      C. vulgaris, for which the growth rate in darkness on a glucose medium remained
      constant for 2 days and then declined to approach zero. Pigment concentrations
      also declined in darkness. Changes in flow rate of 1% CO(2)-in-air from zero to 7
      ml per minute caused a progressive increase in the dark growth rate over a 5-day
      period, but did not maintain growth in the dark. Rates above 7 ml per minute
      produced no changes in growth rates.White light intensities below the
      compensation point of the alga maintained heterotrophic growth. The saturation
      value for this response was 0.8 muw/cm(2). White light also initiated growth in
      nongrowing cultures transferred from darkness to light.The action spectrum for
      heterotrophic growth indicated a porphyrin as the active pigment. Light in the
      425 mmu region was 4 times as effective as white light in stimulating
      heterotrophic growth. A secondary peak of growth stimulation occurred in the 575
      mmu region.The respiration of glucose by the alga was stimulated by low
      intensities of white light. This response was not immediate, but was clearly
      present after the third day of incubation.Malonate and cyanide were inhibitory to
      growth of C. vulgaris on inorganic medium or glucose medium under 300 ft-c of
      white light. These data suggested that succinic dehydrogenase and cytochrome
      oxidase systems were present.Substances inhibitory to growth were excreted into
      the medium under dark-growth conditions, and 2 of these substances were
      indentified as formic and acetic acids.The evidence suggested that respiration of
      glucose cannot proceed for an extended period of time in darkness. The reason for
      this is postulated to be the lack of a cytochrome or a cytochrome precursor.

PMID- 16656235
TI  - Transpiration, water absorption, and internal water balance of cotton plants as
      affected by light and changes in saturation deficit.
AB  - In controlled environment studies of cotton plants (Gossypium barbadense L.) a
      light-induced acceleration of transpiration upset the water balance established
      in the dark because of a lag in water absorption. A plant-water deficit could be
      generated either by sudden illumination at a given saturation deficit (sd) of the
      air, or by raising the sd in conjunction with illumination, without different
      effects.Direct water balance measurements were confirmed in every experiment by
      beta ray gauge detection of changes in leaf-water content resulting from unequal
      gain and loss of water by the whole plant.Recovery from the initial loss of
      turgidity always was faster and more complete at the higher than at the lower
      values of sd. Recovery occurred even in the light at the higher values of sd, but
      was enhanced by return to darkness and a lower sd, which at times resulted in
      superhydration.Rehydration in the light could be attributed to at least 2
      processes: A) a diminished transpiration rate if earlier water loss was
      sufficient to induce stomatal closure, and B) an increased rate of water
      absorption. The data suggest that a water deficit, temporary or persisting, does
      not cause a significantly lowered transpiration rate; thus, recovery must depend
      on increased absorption. The communicative link between the 2 processes appears
      weak, transmitting strong signals only.

PMID- 16656236
TI  - Incorporation of a kinin, N, 6-benzyladenine into soluble RNA.
AB  - Kinin requiring tobacco and soybean tissues incubated on a medium containing N,6
      benzyladenine-8-C(14) incorporated C(14) into several RNA components including
      adenylic and guanylic acids. About 15% of the label taken up by the tissues
      appeared in RNA while the remainder was distributed among several metabolites in
      the soluble, nonpolynucleotide fraction. Tissue grown on a kinin labeled in the
      side chain (N,6-benzyladenine-benzyl-C(14)) also incorporated a small, but
      nevertheless repeatable, amount of radioactivity into minor RNA
      components.Ultracentrifugation studies and methylated albumin chromatography
      indicated that the bulk of the label from benzyladenine-benzyl-C(14) is in
      soluble RNA. Approximately 50% of the C(14) in soluble RNA is in a component
      which has chromatographic properties like that of benzyladenine.It is suggested
      that the biological action of the kinins may hinge on their providing substituted
      bases in RNA in tissues which through differentiation no longer synthesize RNA
      methylating enzymes. As an alternative it was hypothesized that a small amount of
      benzyladenine was incorporated into a m-RNA, acting there as a derepressing
      agent, perhaps by preventing its normal repressing function.

PMID- 16656237
TI  - Auxin transport in explants of coleus.
AB  - alpha-Naphthaleneacetic acid-C(14), labeled in the carboxyl group, was applied in
      blocks of agar to the distal and to the proximal (either apical or basal) ends of
      explants of Coleus. The radioactivity in receiver blocks at the opposite ends was
      measured. Acropetal transport was slight, only 4% of the basipetal
      transport.Translocation of NAA-C(14) was polar in basipetal direction. Only 1.4%
      of the radioactivity lost from donor blocks at the apical position reached the
      receiver blocks; the greatest part remained in the tissue and was immobilized
      there. All activity found in receiver blocks at the basal end appeared to be
      still in the form of NAA. There were no differences between petiole tissue and
      stem tissue, so far as the transport of NAA is concerned.

PMID- 16656238
TI  - Separate action spectra for the two photochemical systems of photosynthesis.
AB  - Action spectra have been obtained which are believed to represent the 2
      photochemical systems in the marine green alga, Ulva lobata. Measurement of
      transient rates of O(2) uptake in the presence of DCMU furnished the data for the
      spectrum representing system I. The action spectrum for system II refers to O(2)
      evolution rates after the Ulva was pretreated in an atmosphere of high O(2)
      concentration. Tissue responses after high O(2) exposure suggests an inhibition
      of the photosynthetic functioning of system I.

PMID- 16656239
TI  - Stomatal density and responsiveness of banana fruit stomates.
AB  - Determination of stomatal densities of the banana peel (Musa acuminata L. var
      Hort. Valery) by microscopic observations showed 30 times fewer stomates on fruit
      epidermis than found on the banana leaf. Observations also showed that peel
      stomates were not laid down in a linear pattern as on the leaf.It was
      demonstrated that stomatal responses occurred in banana fruit. Specific
      conditions of high humidity and light were necessary for stomatal opening: low
      humidity and darkness were necessary for closure. Responsiveness of the stomates
      continued for a considerable length of time after the fruit had been severed from
      the host.

PMID- 16656240
TI  - Role of oxygen fixation in hydroxyproline biosynthesis by etiolated seedlings.
AB  - Etiolated maize and soybean seedlings were grown for several days in atmospheres
      enriched with O(18). Hydroxyproline subsequently isolated from the seedlings by
      column and thin-layer chromatography was labeled with excess O(18), but proline
      was not. Control experiments in which seedlings were grown in H(2)O(18) and
      unlabeled atmospheres demonstrated that neither proline nor hydroxyproline was
      labeled with excess O(18). It was concluded that oxygen fixation is an essential
      feature of hydroxyproline biosynthesis in these seedlings, and that the hydroxyl
      oxygen atom in hydroxyproline is derived from molecular oxygen and not from
      water; similar results have been reported previously for sycamore cell
      suspensions.

PMID- 16656241
TI  - Differentiation between indoleacetic Acid and the citrus auxin by column
      chromatography.
AB  - A gradient elution column chromatography technique and a step-wise technique
      succeeded in differentiating between IAA and the citrus auxin. IAA was eluted
      ahead of the citrus auxin in both systems. The highest Avena curvature ever
      obtained from the citrus auxin occurred after the auxin had passed through the 2
      purification techniques and a paper chromatography step. This is probably due to
      the elimination of inhibitors. Fluorometric assay, Ehrlich's reaction, thin-layer
      chromatography, and biological assay were used for the detection of IAA or citrus
      auxin in the column eluates.

PMID- 16656242
TI  - Purification and properties of apple fruit malic enzyme.
AB  - Malic enzyme was isolated and purified from mature apple fruits (Malus
      sylvestris, Miller) by utilizing procedures probably applicable to other soluble
      enzymes in this and similar tissues.The physical properties of apple fruit malic
      enzyme are similar to those reported for malic enzyme from other plant and animal
      sources. It is specific for l-malate, TPN and requires a divalent cation for
      activity. In contrast to the pigeon liver enzyme, supplemental TPN is not
      required for oxalacetic decarboxylase activity of the fruit enzyme. The pH
      optimum of the malic enzyme varied with the l-malate concentration and the nature
      of the divalent cation present. d-Malate activated the oxidation of l-malate at
      rate-limiting concentrations.

PMID- 16656243
TI  - Imbibition period as the critical temperature sensitive stage in germination of
      lima bean seeds.
AB  - Lima bean seeds (Phaseolus lunatus L.) and excised embryonic axes can be injured
      during imbibition at temperatures below 25 degrees . The early imbibitional stage
      is critical; imbibition at 25 degrees followed by low temperature exposure does
      not cause injury. Sensitivity to chilling injury is conditioned by the pre
      harvest seed history. Low vigor (bleached) seeds are most sensitive to injury,
      the effects of which can be intensified by restricted oxygen supply during early
      axis growth. The seed coat, by preventing water uptake, can permit the seed to
      avoid injury. This protective mechanism is most effective at low temperature and
      high moisture stress. Immediately following low temperature imbibition, injured
      axes lose organic materials, probably nucleotides. This organic leachate is a
      potential influence on soil microorganisms and, together with the temperature
      sensitivity, vigor, and seed coat effect undoubtedly is important in controlling
      the potential variability in germination shown by a seed population.

PMID- 16656244
TI  - Monovalent cations and growth regulation. I. Growth responses in cucumber
      hypocotyl segments.
AB  - The elongation of etiolated cucumber (Cucumis sativus L.) hypocotyl segments was
      stimulated by KCl and a number of other potassium salts at a concentration of
      0.02 n K(+). The effect of KCl was not evident until 14 hours after the beginning
      of treatment.NaCl, LiCl, and RbCl enhanced elongation of the segments, and their
      dosage-response curves were similar to that for KCl. At supraoptimal
      concentrations (>/= 0.05 m), LiCl inhibited segment growth. CsCl was inhibitory
      at all concentrations tested and was thus the only alkali metal cation to lack
      growth-promoting activity in this system. NH(4)Cl also promoted elongation, but
      not as effectively as did the alkali cations.CaCl(2), CoCl(2), and MgCl(2) did
      not enhance growth when tested at the same concentrations as the monovalent
      cations. CoCl(2) promoted strongly at 10(3)m, and NiCl(2) was slightly active at
      10(-4)m.It is suggested that the nutritional requirement for K in higher plants
      results from a specific involvement in certain enzyme systems and from a
      relatively nonspecific role related to the elongation response described here.

PMID- 16656245
TI  - Inhibition of the growth of peas by tris-(2-diethylaminoethyl)-phosphate
      trihydrochloride.
AB  - The effects of Tris-(2-diethylaminoethyl)-phosphate trihydrochloride (SK&F 7997
      A(3)) on the development of 4 varieties of Pisum sativum were investigated. The
      compound inhibited shoot elongation of all 4 varieties by as much as 50% or more
      when seeds were soaked in solutions of the inhibitor for 12 hours before
      planting. Seed treatment also affected flowering by causing an increase in the
      number of nodes to the first flower in the early varieties Little Marvel and
      Alaska. The number of nodes preceding the first flower in the late varieties
      Dwarf and Tall Telephone was not affected by high concentrations of SK&F 7997
      A(3), but low concentrations appeared to cause a slight reduction in the number
      of nodes to flower.The inhibitor had little effect on growth when applied to
      established seedlings; some slight inhibition was noted when high doses were
      applied to the shoot tip.SK&F 7997-A(3) suppressed the growth response of dwarf
      and tall peas to exogenous GA(3). The compound did not inhibit biosynthesis of
      gibberellin by Fusarium moniliformc when present in shaken liquid cultures at
      concentrations as high as 10 mg/ml. The inhibitor suppressed the action of
      applied GA(3) on shoot elongation when the 2 chemicals were applied in 3 ways: 1)
      inhibitor on lowermost compound leaf and GA(3) on shoot tip; 2) GA(3) on
      lowermost leaf and inhibitor on shoot tip; and 3) soaking of seeds in the 2
      compounds combined for 12 hours prior to planting. The third method of dual
      treatment yielded evidence that SK&F 7997-A(3) interacts noncompetitively with
      GA(3) in the regulation of shoot elongation.

PMID- 16656246
TI  - A system for measuring penetration of radioactive ions across roots of intact
      plants.
AB  - A technique was developed for estimating penetration of P(32) across roots of
      intact plants (Phaseolus vulgaris) by measuring the level of isotope in the xylem
      stream. Penetration was defined as movement from the root surface to the xylem
      sap. The xylem sap measurement for P(32) was made in the stem as the material
      ascended the plant in the transpiration stream. Stems were held near 0 degrees to
      arrest metabolic concentration of isotope adjacent to the xylem column. A 3 layer
      environment control system was constructed to allow stem chilling in a manner
      that would not interfere with the environments of the roots or foliage. Despite
      these precautions, some extra-xylary build-up of (32)P occurred in the chilled
      stem. The mathematical function of the extra-xylary fraction was derived, and the
      difference between this value and total P(32) in the stem represented xylem sap
      isotope.

PMID- 16656247
TI  - Ion Absorption and Retention by Chlorella Pyrenoidosa. II. Permeability of the
      Cell to Sodium and Rubidium.
AB  - The Na and Rb permeability of Chlorella pyrenoidosa were estimated from the rates
      of radioisotope self-diffusion.The isotopic exchange in absence of net ionic
      movements followed first order kinetics. This suggested that for sodium, which
      reached isotopic equilibrium in approximately 90 minutes, the cell behaved as 1
      compartment with respect to isotopic exchange. Rubidium in 180 minutes approached
      isotopic equilibrium by 67%; thus, the existence of a single compartment for Rb
      has not been demonstrated. Net fluxes, calculated from the isotope exchange data,
      and expressed on a dry weight and surface area base showed that Na fluxes were
      approximately 7 times larger than Rb fluxes. Net Na fluxes of 90 milli
      equivalents per 100 g dry weight per hour were far in excess of the observed
      maximum net accumulation of Na. However, Rb fluxes of 13 milliequivalents per 100
      g dry weight per hour were of similar magnitude as the rate of Rb accumulation.
      Thus, permeability could be a limiting factor for Rb but not for Na accumulation.
      Sodium and Rb fluxes in absence of net ionic movements were inhibited by low
      temperature, dark air and dark N(2) conditions. This change in flux rates was
      explained mainly on the basis of metabolically dependent changes in the cell
      surface layers.Isotope fluxes of Rb were drastically reduced in dark air and dark
      N(2) in the absence or presence of net cation movements. Dark N(2) essentially
      eliminated net cation accumulation, whereas dark air had relatively little effect
      on the net K and Rb accumulation by Chlorella. Thus the 2 major factors involved
      in net cation accumulation in the Chlorella cell, permeability and processes
      leading to cation retention, respond differently to metabolic inhibition
      permitting a separation of these 2 important aspects of cation accumulation.

PMID- 16656248
TI  - Swelling and contraction of corn mitochondria.
AB  - A survey has been made of the properties of corn mitochondria in swelling and
      contraction. The mitochondria swell spontaneously in KCl but not in sucrose. Aged
      mitochondria will swell rapidly in sucrose if treated with citrate or EDTA.
      Swelling does not impair oxidative phosphorylation if bovine serum albumin is
      present.Contraction can be maintained or initiated with ATP + Mg or an oxidizable
      substrate, contraction being more rapid with the substrate. Magnesium is not
      required for substrate powered contraction. Contraction powered by ATP is
      accompanied by the release of phosphate. Oligomycin inhibits both ATP-powered
      contraction and the release of phosphate. However, it does not affect substrate
      powered contraction. Substrate powered contraction is inhibited by electron
      transport inhibitors. The uncoupler, carbonyl cyanide m-chlorophenyl hydrazone,
      accelerates swelling and inhibits both ATP-and substrate-powered contraction.
      However, the concentrations required are well in excess of those required to
      produce uncoupling and to accelerate adenosine triphosphatase; the concentrations
      required inhibit respiration in a phosphorylating medium.Phosphate is a very
      effective inhibitor of succinate-powered contraction. Neither oligomycin nor Mg
      affects the phosphate inhibition. Phosphate is less inhibitory with the ATP
      powered contraction.The results are discussed in terms of a hypothesis that
      contraction is associated with a nonphosphorylated high energy intermediate of
      oxidative phosphorylation.

PMID- 16656249
TI  - Effect of Growth Regulators on CO(2) Assimilation in Leaves, and its Correlation
      with the Bud Break Response in Photosynthesis.
AB  - Experiments have been done to confirm the previously reported effect of
      indoleacetic acid (IAA) on the rate of CO(2) assimilation in bean leaves. It was
      shown that spraying the leaves of a variety of plants caused an increase in the
      rate of CO(2) assimilation from 30% to 100% during the half-hour to 1 hour period
      following spraying. The only plant tested which did not show such an effect was
      corn.The breaking of dormancy of axial buds in the bean plant was correlated with
      an increase in the rate of CO(2) assimilation in adjacent leaves for a brief
      period of time. It has been shown that IAA solution sprayed on 1 leaflet of a
      leaf can cause an increase in the rate of CO(2) assimilation in the other
      leaflets, and that IAA applied to the cut stem of a leaflet or a developing bud
      can be transported to adjacent leaves and cause an increase in the CO(2)
      assimilation rate. The reaction caused by IAA is very similar to that caused by
      the breaking of dormancy of a bud. This indicates that the bud break response in
      CO(2) assimilation in leaves is caused by auxin synthesized in a bud as it begins
      to grow, and exported into adjacent leaves.

PMID- 16656250
TI  - Vegetative Response of Saltcedar (Tamarix pentandra Pall.) to Photoperiod.
AB  - Saltcedar (Tamarix pentandra Pall.) stem cuttings responded vegetatively to
      various photoperiods of 11-, 14-, 17-, and 8 + 1-hour duration. Total stem
      length, average stem length, cuticle thickness, and xylem vessel member outside
      diameter were significantly maximal under a 14-hour photoperiod and less under
      photoperiods above and below this level. Numbers of stems and roots produced were
      significantly less in an 11-hour than under a 14-hour photoperiod; but neither
      was significantly different from responses under 17- and 8 + 1-hour photoperiods.
      Vegetative photoperiodic responses, except for cuticle thickness, were affected
      by a photoperiodic after-effect produced by cuttings collected on various dates.
      Average stem length, total stem length, and number of stems produced were
      significantly correlated with field photoperiods from November to May.

PMID- 16656251
TI  - Metabolic changes associated with vernalization of wheat. I. Carbohydrate and
      nitrogen patterns.
AB  - A spring wheat (Triticum aestivum) and an obligate winter wheat (Triticum
      compactum) variety were each grown for 5 weeks in controlled environments at 2
      degrees and 25 degrees . The threshold for flower induction in the winter wheat
      was 4 to 5 weeks at 2 degrees , whereas the spring wheat had no low temperature
      requirement for flowering. Changes in the levels of carbohydrate and nitrogen
      fractions in the wheat leaves were determined during their growth in the cold and
      warm environments. There was an enhanced accumulation of the 5 carbohydrate
      fractions in both wheat varieties grown at 2 degrees compared to 25 degrees .
      Highly significant differences in the levels of sucrose, oligosaccharides, and
      starch were found between the spring and winter varieties grown at 2 degrees .
      The winter wheat seedlings grown at 2 degrees accumulated much more of these
      carbohydrates than the corresponding spring wheat. The carbohydrate patterns in
      both varieties grown at 25 degrees were nearly identical except for the final 2
      weeks of growth.The level of nitrogenous substances in the tissues grown at 2
      degrees was much higher than in the corresponding tissues grown at 25 degrees .
      The only significant difference between the spring and winter varieties was in
      the soluble protein fraction. This fraction rose nearly 3-fold in the winter
      variety grown at 2 degrees , whereas it remained nearly constant in the similarly
      grown spring wheat. Most of the changing chemical patterns observed in relation
      to the vernalization treatment appear to be metabolic alterations associated with
      low temperature rather than alterations directly related with the vernalization
      response.

PMID- 16656252
TI  - Control of invertase synthesis in sugar cane. Loci of auxin and glucose effects.
AB  - In tissue slices from rapidly expanding internodes of sugar cane the vacuolar
      invertase level is a function of the balance between synthesis and destruction.
      The enzyme is destroyed in the tissue at an approximately constant rate with a
      half time of 2 hours. Invertase synthesis is regulated by both auxin and glucose.
      From studies with inhibitors of protein and RNA synthesis we conclude that auxin
      alters the rate of synthesis and glucose increases the rate of destruction of
      messenger RNA required for the production of invertase.

PMID- 16656253
TI  - Metabolic regulation in diseased leaves. I. The respiratory rise in barley leaves
      infected with powdery mildew.
AB  - Photosynthetic and respiratory activities have been measured in leaves of Hordeum
      vulgare L. var. Manchuria (barley) after infection with Erysiphe graminis var.
      hordei (powdery mildew). Two isogenic lines, one resistant to infection and the
      other highly susceptible, were examined.These isogenic lines showed very
      different physiological responses following infection. Photosynthesis and the
      chlorophyll content of resistant leaves was unaffected by infection. Respiration
      increased slightly and this was accompanied by small increases in activities of
      enzymes of glycolysis, the pentose-P pathway and the tricarboxylic acid cycle.The
      infection of susceptible leaves resulted in a slight increase in photosynthesis
      48 hours after inoculation, but subsequently there was a progressive decrease in
      the photosynthesis of these leaves compared with that of noninfected leaves. The
      capacity of infected leaves for partial reactions of photosynthesis such as the
      Hill reaction and the photoreduction of nicotinamide adenine dinucleotide
      phosphate (NADP(1)) decreased during the later stages of infection. The levels of
      chlorophyll, NADPH-diaphorase and aldolase also declined. There was no detectable
      difference in the respiration of infected and noninfected leaves until 48 hours
      after inoculation. After this time, the infected leaves showed a higher
      respiration, the maximum difference occurring about 144 hours after inoculation.
      The respiratory increase was not accompanied by significant changes in the levels
      of enzymes of glycolysis and the tricarboxylic acid cycle with the exception of
      malate dehydrogenase which was lower in infected leaves. In contrast, the
      activities of glucose-6-P dehydrogenase and 6-P-gluconate dehydrogenase showed
      changes similar to that observed for respiration.The respiration and the
      activities of glucose-6-P dehydrogenase and 6-P-gluconate dehydrogenase did not
      increase in infected leaves of etiolated plants, even when excellent growth of
      the fungus was established by growing the plants in White's basal medium
      supplemented with sucrose. The respiration of a susceptible mutant barley (the
      yellow-green virescent mutant of the variety Himalaya) when grown in the light at
      11 degrees was not changed by infection although the characteristic respiratory
      rise occurred in plants grown at 15 degrees . At the lower temperature
      chloroplasts fail to develop in this mutant, although development is normal at 15
      degrees .It is suggested that the pathogen is not directly responsible for the
      increase in respiration in green leaves, rather that this is a response in the
      host cells to a loss of photosynthetic capacity.

PMID- 16656254
TI  - Germination of phaseolus vulgaris I. Resumption of axis growth.
AB  - Growth of the excised axis of Phaseolus vulgaris L. (var. White Marrowfat) begins
      after a 7-hour incubation in buffer or water at 26 degrees . Growth, as measured
      by axis elongation or fresh weight increase, is linear for at least 8 hours with
      a resultant fresh weight increase of approximately 65%. Cell elongation begins 4
      or 5 hours prior to cell division and 5 or 6 hours prior to radicle protrusion in
      the intact seed.The initiation of axis elongation is apparently dependent on
      synthesis of RNA and protein. Both actinomycin D and puromycin inhibit the
      initiation of elongation. Actinomycin I) inhibits the incorporation of ATP-8
      C(14) into axis RNA and C(14)-leucine into protein, while puromycin inhibits the
      incorporation of C(14)-leucine into axis protein.The respiratory rate of the axes
      increases sharply at about the time of initiation of cell elongation.
      Dinitrophenol initially increases O(2) uptake by the axes, but at the end of 15
      hours the rates of O(2) uptake by control or dinitrophenol-treated axes are
      approximately the same.

PMID- 16656255
TI  - On Autotropism in Botrytis: Measurement Technique and Control by CO(2).
AB  - The mutual orientation of the germination of nearby pairs of Botrytis spores
      growing in a simple, dilute medium was studied. If the medium is equilibrated
      with room air, they show a very strong tendency to germinate both toward each
      other and in a cis arrangement, i.e., toward the same side of the line joining
      their centers. If the medium is equilibrated with air enriched with 0.3% or 3%
      CO(2), (i.e., 10 or 100 times the normal CO(2) concentration) then the cells show
      an equally strong tendency to germinate away from each other. The interaction
      shows little dependence upon pH.

PMID- 16656256
TI  - Nonessentiality of boron in fungi and the nature of its toxicity.
AB  - AN INVESTIGATION WAS UNDERTAKEN TO DETERMINE WHETHER ANY OF THE FOLLOWING FUNGI
      HAD A REQUIREMENT FOR BORON (B): Saccharomyces cerevisiae, Aspergillus niger,
      Neurospora crassa, and Penicillium chrysogenum. Boron was unessential, and hence
      a study was made of the concentrations of B that reduced the growth of S.
      cerevisiae and P. chrysogenum and the mode of action of the B toxicity. Fifty and
      4000 mg B/liter, respectively, significantly (5% level) reduced the growth of the
      latter 2 species.In both, glycolysis appeared to be inhibited by toxic levels of
      B, since the cells accumulated fructose-1,6-diP and ADP, but were low in
      glyceraldehyde-3-P and ATP. With S. cerevisiae growing on glucose, 150 mg B/liter
      significantly reduced CO(2) evolution. When glyceraldehyde was substituted for
      glucose, CO(2) evolution and O(2) consumption were unaffected by this level of
      B.Aldolase was suspected of being inhibited by high B, and this was confirmed
      using a crude aldolase extract from S. cerevisiae and purified rabbit muscle
      aldolase. The inhibition of aldolase by B was uncompetitive.With aldolase
      activity being reduced by toxic levels of B, the fungi were apparently unable to
      utilize carbohydrates at a rate sufficient to maintain the metabolic processes
      involved in growth and reproduction.

PMID- 16656257
TI  - Bacteria, antibiotics and amino Acid incorporation into maize endosperm protein
      bodies.
AB  - The incorporation of C(14)-leucine into protein bodies isolated from developing
      maize endosperm was studied. Protein bodies which incorporated significant
      amounts of C(14)-leucine were found to be contaminated with bacteria, while
      protein bodies prepared with sterile techniques incorporated C(14)-leucine at
      very low rates.Streptomycin, penicillin, puromycin, and actinomycin did not
      completely inhibit the bacterial incorporation, while chloramphenicol was an
      effective inhibitor.

PMID- 16656258
TI  - Chloroplast Fatty Acid transformations in nitrogen-deficient and senescent
      tissues.
AB  - The fatty acids of plastids from several types of mineral-deficient and senescent
      tissues were analyzed. Incorporation of acetate into long-chain fatty acids of
      leaf tissue and of plastids from nitrogen-deficient and normal plants was
      determined. In general, the senescent and nitrogen-deficient chloroplasts
      contained a higher ratio of saturates to unsaturates than did plastids from
      younger tissues and from tissues grown on a complete nutrient.Nitrogen-deficient
      leaf tissue and plastids were capable of rapidly incorporating acetate into some
      of the fatty acids, especially palmitic and oleic acids. However, the comparative
      rate of acetate incorporation into linolenic acid in nitrogen-deficient
      chlorophyllous tissue was less than in tissue grown on a complete nutrient. With
      the addition of UDP-glucose to a reaction mixture containing added cofactors for
      noncyclic photosynthetic phosphorylation the relative incorporation of acetate
      into linolenate as compared to palmitate was increased in both the nitrogen
      deficient and normal leaf tissue. This would indicate that nitrogen-deficient
      tissues have the enzymic systems for forming long-chain fatty acids but that the
      reduced photosynthesis limits the amount of precursors for the formation of
      lipids, especially galactolipids. However, nothing is known about the rate of
      fatty acid degradation under these conditions.

PMID- 16656259
TI  - Bound indoleacetic Acid in Avena coleoptiles.
AB  - When C(14) carboxyl indoleacetic acid (IAA) is transported through Avena
      coleoptile sections a fraction of the activity becomes bound. The nature of this
      bound IAA has been investigated. Upon extraction with solvents and chromatography
      a substance having the R(F) of IAA in 4 solvents was detected. No evidence could
      be found for the formation of indoleacetyl conjugates. In pea stem sections
      subjected to a similar experimental regime good evidence was obtained for the
      occurrence of conjugates. When IAA was supplied exogenously to coleoptile
      sections floating in solutions the occurrence of conjugates was shown to be
      dependent on the presence of the primary leaf. In its absence no conjugates could
      be detected.On grinding coleoptile sections and subsequent centrifugation at 240
      x g the radioactivity was found to be in the tissue fraction as opposed to the
      supernatant. The radioactivity cannot be removed from the tissue by extraction
      with water, buffer solution or treatment with ribonuclease. It is readily removed
      by 10% urea, crystalline trypsin and chymotrypsin. It is therefore concluded that
      IAA becomes bound to a protein. Bound IAA does not appear to be able to cause
      growth in Avena coleoptile sections.

PMID- 16656260
TI  - Production of volatile amines and skatole at anthesis in some arum lily species.
AB  - The odoriferous compounds produced at the time of flowering by the inflorescences
      of 5 arum lily species were condensed in dry ice traps. The components of the
      condensates were separated by paper chromatography and identified on the basis of
      position and color reactions in comparison with known compounds. The
      concentration of free amino acids in the appendix of Sauromatum guttatum Schott
      increased 20-fold during flowering.

PMID- 16656261
TI  - Hydrogenase mediated nitrite reduction in chlorella.
AB  - The assay of the hydrogenase of glucose-grown cells of Chlorella pyrenoidosa,
      strain 7-11-05 by means of nitrite reduction with molecular hydrogen is
      described. The hydrogenase of Chlorella shows maximum activity immediately after
      equilibration in the hydrogen atmosphere. The hydrogenase mediated reduction of
      nitrite to ammonia requires the presence of CO(2). However, at pH 6.4. when the
      reaction proceeds optimally, there is apparently sufficient retention of
      metabolic CO(2) to support the reaction, which goes to completion, at near
      maximum rates.Reduction of nitrite in the hydrogenase system when CO(2) is
      present results in the uptake of 3 moles of H(2) per mole of nitrite and ammonia
      is the product. When CO(2) is absent or limiting, ammonia is also formed from
      nitrite but with the uptake of less than the stoichiometric amount of H(2). It is
      concluded that CO(2) is essential for the uptake of H(2), and that in the absence
      of CO(2) internal hydrogen donors support nitrite reduction.The possibility that
      CO(2) exerts a catalytic effect in all reductions mediated by hydrogenase in
      algae is considered, and a further hypothesis, that hydrogenase arises from that
      portion of the photosynthetic machinery which also shows a catalytic requirement
      for CO(2), is proposed.

PMID- 16656262
TI  - Studies of Frost Hardiness in Woody Plants. II. Effect of Temperature on
      Hardening.
AB  - The effect of temperature on hardening was studied at temperatures ranging from 0
      degrees to -20 degrees using twigs of willow and poplar. In October and in late
      April when the twigs are not very frost hardy, hardening at 0 degrees produced a
      considerable increase in their frost hardiness, although the effectiveness of
      hardening at 0 degrees decreased with a decrease in the environmental
      temperature. In twigs which could withstand continuous freezing without injury,
      hardening at -3 degrees to -5 degrees was most effective in increasing the frost
      hardiness of the twigs. Below -20 degrees , only negligible increase was observed
      either in frost hardiness or sugar content.The rate of starch to sugar conversion
      differed remarkably in different twig tissues. The starch in xylem was more
      slowly converted to sugar than that in the cortex. The optimum temperature for
      converting starch into sugar during frost hardening was also found to be -3
      degrees to -5 degrees . In addition, the greater the effectiveness of the
      hardening treatment, the greater the rate of conversion from starch to sugar. The
      frost hardiness of a twig is closely related to the sugar content of the twig,
      especially in the xylem.

PMID- 16656263
TI  - Relationship of lipid metabolism to the respiration and growth of pea stem
      sections.
AB  - Biologically active lipids increase the growth of pea stem sections within 3
      hours at the same time their respiration is increased and their growth rate is
      more than that of the intact plant. The greater final length of the intact
      internode is due to a longer growth period.BOTH ACTIVE AND INACTIVE LIPIDS ARE
      RAPIDLY TAKEN UP AND ENTER ALL MAJOR METABOLIC FRACTIONS: among centrifugal
      fractions methyl oleate tends to label those that contain metabolically active
      membranes. It is concluded that lipids active in the bioassay are probably the
      effective molecules at the subcellular site of action.No direct effect of lipids
      on isolated mitochondria could be shown. The respiration of stem tissue was not
      influenced by dinitrophenol and carbonyl cyano m-chlorophenyl hydrazone although
      dinitrophenol inhibited growth. Lipid-induced respiration was sensitive to these
      agents as well as to cyanide, indicating cytochrome oxidase is probably
      involved.The promotion of growth and respiration by lipids is not linked to
      protein synthesis, since actinomycin D, puromycin and cycloheximide failed to
      inhibit the respiratory increase even though strongly limiting amino acid
      incorporation into protein. It is most likely that the effect of lipids on growth
      is due to their promotion of respiration.

PMID- 16656265
TI  - Translocation in colored light.
AB  - The translocation of (14)C-photosynthate in detached blades of sugarcane was
      studied under illumination from red, green, blue, and cool-white fluorescent
      lamps; under far-red illumination from the sun, and from incandescent lamps; and
      in total darkness.The percentage of basipetal translocation and the accumulation
      against the concentration gradient were stimulated by light from the red or blue
      lamps more than by green or cool-white fluorescent illumination.Basipetal
      translocation took place equally well in red light lacking blue irradiation and
      in blue light. Since the action spectrum for light-induced change in viscosity is
      a typical blue-type spectrum, the effect of light upon translocation is not due
      merely to changes in the physicochemical properties of protoplasm.Basipetal
      translocation took place in red light lacking blue irradiation better than in
      cool-white fluorescent light, which may suggest a red stimulation of
      translocation.Illumination in the far-red region of the spectrum did not support
      basipetal translocation but acted like total darkness.Because of the wide
      emission characteristics of the fluorescent lamps employed, it is impossible to
      decide whether a chlorophyll-like system or some other pigment is involved in the
      light stimulation of phototranslocation.Whatever the activating wavelength and
      whatever the pigment system involved, these results show that the
      phototranslocation of sucrose in the phloem is influenced by the quality of
      illumination.

PMID- 16656266
TI  - Composition of guttation fluid from rye, wheat, and barley seedlings.
AB  - This work was undertaken to determine the kinds and amount of substances that
      would account for the previously demonstrated differential growth of Claviceps
      purpurea on guttation fluids from Rosen rye, Genesee wheat, and Traill barley
      seedlings. Chromatographic methods were used for determining amino acids and
      sugars, spot tests and spectrometric methods for inorganic materials, and
      microbiological methods for vitamins.Total sugar content is about equal in rye
      and barley fluids, but lower in wheat. Glucose is the principal sugar component
      of the rye and barley fluids and galactose highest in wheat. Most of the amino
      acid in all 3 fluids is aspartic acid or asparagine. Barley fluid is far higher
      than the other 2 in total amino acids, with wheat the lowest. Most inorganic
      elements are found to be highest in barley and lowest in wheat, with the
      exception of iron where rye is highest and barley lowest. Barley fluid is highest
      in choline, p-aminobenzoic acid, thiamine, and uracil, while rye is highest in
      inositol and pyridoxine. Wheat is much lower than the other 2 in choline and
      inositol.

PMID- 16656267
TI  - Stimulation of ethylene production in apple tissue slices by methionine.
AB  - Methionine can induce more than a 100% increase in ethylene production by apple
      tissue slices. The increased amount of ethylene derives from carbons 3 and 4 of
      methionine. Only post-climacteric fruit tissues are stimulated by methionine, and
      stimulation is optimum after 8 months' storage. Copper chelators such as sodium
      diethyl dithiocarbamate and cuprizone very markedly inhibit ethylene production
      by tissue slices. Carbon monoxide does not effect ethylene production by the
      slices. These data suggest that the mechanism for the conversion of methionine to
      ethylene, in apple tissues, is similar to the previously described model system
      for producing ethylene from methionine and reduced copper. Therefore, it is
      suggested that one of the ethylene-forming systems in tissues derives from
      methionine and proceeds to ethylene via a copper enzyme system which may be a
      peroxidase.

PMID- 16656268
TI  - DNA from plant mitochondria.
AB  - DNA WAS ISOLATED FROM A MITOCHONDRIAL FRACTION OF EACH OF THE FOLLOWING PLANT
      MATERIALS: Mung bean (Phaseolus aureus) etiolated hypocotyl; turnip (Brassica
      rapa) root; sweet potato (Ipomoea batatas) root; and onion (Allium cepa) bulb. It
      was found that all of these mitochondrial fractions contained DNA, the densities
      of which were identical (rho=1.706 g.cm(-3)). An additional DNA (rho=1.695) band
      found in the mitochondrial fraction of Brassica rapa, was identical to DNA
      separately isolated from the chloroplast-rich fraction. The origin of the second
      DNA from Allium mitochondrial fraction was not identified.Contrary to the
      identity of the mitochondrial DNA, DNA from nuclear fractions differed not only
      with each other but from the corresponding mitochondrial DNA.DNA from Phaseolus
      and Brassica mitochondria showed the hyperchromicity characteristic of double
      stranded, native DNA upon heating; Tm's in 0.0195 Na(+) were the same; 72.0
      degrees . The amount of DNA within the mitochondrion of Phaseolus was estimated
      to be 5.0 x 10(-10) mug; this estimate was made by isolating the mitochondrial
      DNA concomitantly with the known amount of added (15)N(2)H B. subtilis DNA
      (rho=1.740). Approximately the same amount of DNA was present in the
      mitochondrion of Brassica or Ipomoea.

PMID- 16656269
TI  - Sucrose density gradient distribution of mitochondrial protein and enzymes from
      preclimacteric and climacteric pears.
AB  - Mitochondrial fractions isolated from pears (Pyrus communis L.) at the
      climacteric minimum and peak were subjected to sucrose density gradient
      centrifugation. The distribution of protein and specific activities of 3 enzymes
      from this mitochondrial fraction were investigated.Cytochrome oxidase specific
      activity remained associated with the particulate fraction and increased slightly
      during the period in which respiration of the whole fruit reached its climacteric
      peak. Catalase and acid phosphatase specific activity was associated with both
      the particulate and the least dense region of the gradient and decreased with
      postharvest ripening.Evidence for several differences between the subcellular
      behavior of catalase and acid phosphatase from pear tissue compared to their
      counterparts isolated from mammalian cells is discussed. A general shift of
      maximum specific enzymic activities and protein distribution to lighter regions
      of the density gradient occurs with ripening, suggestive of diminution in size or
      density of intracellular particles.

PMID- 16656270
TI  - Influence of Iron Chlorosis on Pigment and Protein Metabolism in Leaves of
      Nicotiana tabacum L.
AB  - Experiments were conducted on Nicotiana tabacum, L. to study the relation in the
      grana among chlorophylls, carotenoids, and proteins. The effect of iron chlorosis
      on protein and pigment synthesis was studied at different stages of chlorosis
      using glycine-U-C(14). Pigments were separated by thin layer
      chromatography.Chlorophyll a, chlorophyll b, carotenoid, and protein contents of
      chloroplasts from chlorotic tissue were less than those of normal tissues. A 25%
      decrease in protein labeling and a 45% decrease in chlorophyll labeling was noted
      in deficient tissue compared to normal tissue even before chlorosis was
      perceptible. Both normal and iron deficient leaf discs which received iron in the
      incubation medium incorporated higher amounts of radioactive glycine into
      chlorophyll a and chlorophyll b at all stages of development than their
      respective counterparts not supplied with iron in the incubation medium. The
      presence of iron in the incubation medium reduced the amount of glycine
      incorporated into carotenes and xanthophylls, except where the tissue was
      severely chlorotic. This may be attributed to active competition for glycine
      between the iron-dependent- (chlorophyll) and iron-independent-(carotenoid)
      biosynthetic pathways. Incorporation of glycine into chloroplast pigments was
      lowest at severe chlorosis, probably due to a reduction in the overall enzyme
      activity.

PMID- 16656271
TI  - Effect of oxygen on photosynthesis, photorespiration and respiration in detached
      leaves. I. Soybean.
AB  - The effect of O(2) on the CO(2) exchange of detached soybean leaves was measured
      with a Clark oxygen electrode and infrared carbon dioxide analysers in both open
      and closed systems.The rate of apparent photosynthesis was inhibited by O(2)
      while the steady rate of respiration after a few minutes in the dark was not
      affected. Part of the inhibition of apparent photosynthesis was shown to be a
      result of increased photorespiration. This stimulation of photorespiration by
      O(2) was manifested by an increase in the CO(2) compensation point.The
      differential effects of O(2) on dark respiration (no effect) and photorespiration
      (stimulation) indicated that these were 2 different processes.Moreover the
      extrapolation of the CO(2) compensation point to zero at zero O(2) indicated that
      dark respiration was suppressed in the light at least at zero O(2) concentration.

PMID- 16656272
TI  - Effect of Oxygen on Photosynthesis, Photorespiration and Respiration in Detached
      Leaves. II. Corn and other Monocotyledons.
AB  - The effect of O(2) on the CO(2) exchange of detached leaves of corn (Zea mays),
      wheat (Triticum vulgare), oats (Avena sativa), barley (Hordeum vulgare), timothy
      (Phleum pratense) and cat-tail (Typha angustifolia) was measured with a Clark
      oxygen electrode and infrared carbon dioxide analysers in both open and closed
      systems.Corn leaves did not produce CO(2) in the light at any O(2) concentration,
      as was shown by the zero CO(2) compensation point and the absence of a CO(2)
      burst in the first minute of darkness. The rate of photosynthesis was inhibited
      by O(2) and the inhibition was not completely reversible. On the other hand, the
      steady rate of respiration after a few minutes in the dark was not affected by
      O(2).These results were interpreted as indicating the absence of any measurable
      respiration during photosynthesis. Twelve different varieties of corn studied all
      responded to O(2) in the same way.The other 5 monocotyledons studied did produce
      CO(2) in the light. Moreover, the CO(2) compensation point increased linearly
      with O(2) indicating a stimulation of photorespiration.The implications of the
      lack of photorespiration in studies of primary productivity are discussed.

PMID- 16656273
TI  - Chromatographic degradation of phloridzin.
AB  - Phloridzin, the main phenolic glucoside in apple leaves, has been found to
      undergo transformation during chromatography. When chromatographed repeatedly in
      ammoniacal solvents, at least 2 new derivatives appeared. One of these was
      identified as phloretic acid. When bioassayed in the presence of indole-3-acetic
      acid this substance behaved as though it promoted the destruction of the auxin.
      Comparative bioassay with naphthaleneacetic acid suggested that phloretic acid
      acts on indoleacetic acid destruction via stimulation of indoleacetic acid
      oxidase. However, at low concentration and in presence of a small amount of
      phloridzin it also showed a synergistic effect with indoleacetic acid.A substance
      with the same characteristics was obtained directly from apple leaves, which are
      known to contain phloridzin when the extracts were chromatographed only once in
      the same (alkaline) solvent. While not completely confirmed, this suggests that
      phloretic acid is normally present in apple leaves, where it may affect growth
      there by promoting indoleacetic acid oxidation.

PMID- 16656274
TI  - Effect of gamma radiation on the ripening of bartlett pears.
AB  - Gamma radiation at doses of 300 Krad or more inhibits the ripening of Bartlett
      pears (Pyrus communis L.). Immediately after irradiation there is a transitory
      burst of C(2)H(4), which subsequently declines in fruits subjected to inhibitory
      doses. Ethylene production associated with ripening begins at the same time in
      unirradiated fruits and those subjected to noninhibitory doses, but the latter
      produces much more C(2)H(4) at the climacteric peak. Fruits subjected to
      inhibitory doses produce low levels of C(2)H(4) unless subjected to exogenously
      applied C(2)H(4), whereupon they produce enough of the gas to induce ripening in
      unirradiated fruits.Pears subjected to 300 and 400 Krad of gamma rays did not
      ripen even when held in a flowing atmosphere containing 1000 ppm of C(2)H(4) for
      8 days at 20 degrees . It is concluded that the action of gamma rays on Bartlett
      pears involves both an inhibition of C(2)H(4) production and a decreased
      sensitivity of the fruit to the ripening action of the gas. Ripening of Bartlett
      pears is inhibited by gamma radiation only when applied to preclimacteric fruit.

PMID- 16656275
TI  - Accumulation of phosphate, sulfate and sucrose by excised Phloem tissues.
AB  - Excised petiolar vascular bundles and excised phloem tissues have been shown to
      take up phosphate, sulfate and sucrose by a true accumulation process and against
      high concentration ratios. Phosphate was accumulated principally as inorganic
      phosphate, and sucrose principally as sucrose. The rates of accumulation of the 3
      solutes into the phloem-containing tissues were from 4 to 35 times higher than
      into comparable parenchyma tissue. It is suggested that this active accumulation
      mechanism plays an important role in the phenomenon of phloem transport.THE
      EXCISED VASCULAR, PHLOEM AND PARENCHYMA TISSUES SHOW AN AGING PHENOMENON:
      aerating the excised tissues for 18 hours prior to their use causes marked
      changes in the accumulatory behavior of the tissue. The data suggest that 1
      phosphate accumulation system of low affinity but high capacity exists in fresh
      tissue, and that aging allows the development of a second, additional phosphate
      accumulation mechanism of high affinity and low capacity. A possible role in the
      control of phosphate movement is suggested.

PMID- 16656276
TI  - Sites of accumulation in excised Phloem and vascular tissues.
AB  - Excised pieces of vascular bundle and phloem tissue were allowed to accumulate
      radioactive phosphate and sulfate, and were then sectioned and autoradiographed
      so as to detect the sites of accumulation. Special methods were needed to prevent
      any diffusion of the radioisotope. Some autoradiographs obtained are presented.
      In excised celery vascular bundles, the most radioactive area and hence the most
      actively accumulating tissue was the young secondary phloem at the sides of the
      bundle. In intact plants, the same tissue was the most active in translocating.
      In excised apple phloem there was some variation in behavior, but again the young
      secondary phloem was generally the most actively accumulating tissue.
      Accumulation activities of individual cells in the phloem and vascular tissue
      were compared. It appeared that all cell types, ray, phloem and xylem parenchyma,
      cambial cells and sieve tubes, accumulated at least 5 times more actively than
      did the cortical parenchyma cells. The sieve tubes were among the most actively
      accumulating cells present, accumulating 20 times more actively than the cortical
      parenchyma cells. It is concluded that accumulation processes have a primary role
      to play in the mechanism of phloem transport.

PMID- 16656277
TI  - Photochemical and Nonphotochemical Reactions of Phytochrome in vivo.
AB  - The nonphotochemical reactions of phytochrome in the coleoptiles of dark-grown
      corn seedlings were studied at 3 temperatures: 14 degrees , 24 degrees , and 34
      degrees . The data obtained show that the destruction of P(fr) is the only
      measurable reaction occurring; reversion of P(fr) to P(r) was not found. The
      Q(10)'s (2.7 and 3.5) and zero order kinetics found for the destruction reaction
      are consistent with the hypothesis that the reaction is enzyme-mediated.In vivo
      action spectra for phytochrome transformation in the coleoptiles of darkgrown
      corn seedlings were obtained which agree qualitatively with those obtained by
      other workers for phytochrome-mediated physiological responses and in vitro
      action spectra. In vivo conversion of phytochrome by blue light, as determined
      from spectrophotometric measurements of phytochrome itself, is reported. Action
      peaks for P(r) were found at 667 mmu and in the blue in the region of 400 mmu,
      with a broad shoulder from 590 mmu to 640 mmu. Action peaks for P(fr) were found
      at 725 mmu and in the blue in the region of 400 mmu with a minor peak at 670 mmu,
      and a broad shoulder from 590 mmu to 640 mmu. The ratio of the quantum
      efficiencies of P(r) at 667 mmu and P(fr) at 725 mmu (Phi(r667)/Phi(fr725)) was
      estimated to be 1.0.

PMID- 16656278
TI  - Sulfolipid metabolism in chlorella.
AB  - When S-deficient cells of Chlorella cllipsoidea were incubated in radio-sulfate
      in light or in aerobic darkness for 1 hour, equal amounts of radioactivity were
      found in sulfolipid and glutathione but none was detected in sulfoquinovosyl
      glycerol which is one of the major S-compounds in this alga. No assimilation of
      radiosulfate was observed under anaerobic darkness.To elucidate the function of
      sulfolipid in algal cells uniformly (35)S-labeled Chlorella cells were
      transferred to S-deficient culture medium or unlabeled normal culture medium and
      the changes of radioactivity in sulfolipid and the related compounds were
      followed. A) On incubating (35)S-labeled algal cells in S-deficient medium under
      photosynthetic conditions, the amounts of radioactivity in sulfate,
      sulfoquinovosyl glycerol and sulfolipid decreased rapidly. B) When (35)S-labeled
      cells were cultured photoautotrophically in unlabeled medium, no decrease of
      radioactivity was observed in sulfoquinovosyl glycerol and sulfolipid. C) A
      decrease of (35)S-sulfolipid and an increase of (35)S-sulfoquinovosyl glycerol
      were observed when the uniformly (35)S-labeled algal cells were illuminated in
      CO(2)-free air.When S-deficient Chlorella cells were incubated in (35)S
      sulfolipid under photosynthetic conditions, significant radioactivity was found
      in the insoluble fraction of the cells. A similar result was observed when normal
      Chlorella cells were incubated in (14)C-sulfolipid and CO(2)-free air.It is
      inferred from these observations that sulfolipid is a reservoir of sulfur and
      carbon compounds.In order to ascertain if the sulfolipid is involved in the
      mechanism of photosynthetic oxygen evolution, the rate of photosynthesis was
      measured during the incubation of (35)S-labeled cells in a S-deficient medium.
      Parallelism was not observed between the rate of photosynthetic activity and the
      decrease of sulfolipid.

PMID- 16656279
TI  - Effect of gibberellic Acid on elongation and longevity of coleus petioles.
AB  - The effects of gibberellic acid on the longevity and elongation of variously
      aged, debladed petioles of Coleus blumei were studied, with particular reference
      to the hypotheses 1) that auxin increases longevity by increasing growth, and 2)
      that gibberellic acid acts by increasing the endogenous levels of
      auxin.Gibberellic acid, substituted for the leaf blades, significantly decreased
      longevity of younger petioles, as measured by days or hours to abscission.
      Gibberellic acid also decreased the longevity resulting from 0.1% indoleacetic
      acid. This is the opposite of the effect expected if it is increasing auxin
      levels in the petiole.In its effect on elongation of younger petioles, however,
      gibberellic acid did act in the direction expected if it were increasing
      effective levels of auxin in the petiole. The elongation rate from 0.1%
      gibberellic acid plus 0.1% indoleacetic acid in lanolin was as large or larger
      than that for 1.0% indoleacetic acid.Petioles which were 10 or more weeks old
      (i.e., at positions 5+ below the apical bud were not affected by 0.1% gibberellic
      acid in either longevity or rate of elongation, with or without 0.1% indoleacetic
      acid. Since 1.0% indoleacetic acid increases both longevity and elongation rate
      of these petioles over 0.1% indoleacetic acid, gibberellic acid is clearly not
      acting on older petioles as if it were increasing effective auxin levels).

PMID- 16656280
TI  - CO(2) Fixation in Opuntia Roots.
AB  - Nonautotrophic CO(2) metabolism in Opuntia echinocarpa roots was studied with
      techniques of manometry and radiometry. The roots were grown in a one-quarter
      strength nutrient solution for several days; the distal 2 cm was used for
      physiological studies. The roots assimilated significant quantities of (14)CO(2)
      and appeared to show a crassulacean-type acid metabolism with respect to quality
      and quantity. Most of the (14)C activity was associated with the distal portion
      of the elongating root indicating correlation with metabolic activity. The
      (14)CO(2) assimilation was comparable to a crassulacean leaf succulent, but 3
      times greater than that found for stem tissue of the same Opuntia species.The
      rates of O(2) and CO(2) exchange and estimated CO(2) fixation were 180, 123, and
      57 mul/g per hour. A respiratory quotient of 0.66 was found.The products of
      (14)CO(2) fixation were similar in most respects to reported experiments with
      leaf succulents. Equilibration of the predominant malic acid with isocitric,
      succinic, and fumaric acids was not evident. The latter observation was
      interpreted as metabolic isolation of the fixation products rather than poor
      citric acid cycle activity.A rapid turnover of the fixed (14)CO(2) was measured
      by following decarboxlyation kinetics and by product analysis after a
      postincubation period. The first order rate constant for the steady state release
      was 4.4 x 10(-3) min(-1) with a half-time of 157.5 minutes. Amino acids decayed
      at a more rapid rate than organic acids.

PMID- 16656281
TI  - Iron translocation I. Plant culture, exudate sampling, iron-citrate analysis.
AB  - Plant culture, exudate sampling, and analytical methods designed to ascertain the
      form of iron translocated are presented.Restoration of iron to sunflower plants
      precultured at different Fe levels resulted in exudate iron concentrations
      ranging from 0.2 to 31 x 10(-5)m. Citrate was from 3 to 89 x 10(-5)m. Iron and
      citrate were highest in exudates from iron-deficient plants. Citrate/Fe ratios
      were between 1 and 3 for exudates of deficient plants. Exudate from normal plants
      gave a citrate/Fe ratio of 15.Malate, iron, and a fraction of the citrate in stem
      exudates migrated electrophoretically to similar positions in acetate buffer.
      Extracts of narrow bands from the iron-containing areas gave curves suggesting
      that citrate bound the iron. Citrate that was not combined with iron migrated in
      a slower band. The effect of iron on citrate migration was confirmed in several
      related experiments.The stability of Fe-citrate was demonstrated
      electrophoretically in malate buffer. Citrate retained iron against malate.Data
      given in this paper indicate that citrate binds iron in sunflower exudate. The
      data suggest that citrate carries iron in intact plants.

PMID- 16656282
TI  - Iron Translocation II. Citrate/Iron Ratios in Plant Stem Exudates.
AB  - Stem exudates of sunflower, soybean, cucumber, and tomato were analyzed for
      citrate and iron content. Generally, the lowest iron treatments given at
      decapitation were associated with lowest citrate levels in the exudate and
      intermediate treatments with the highest citrate levels. Citrate reached 6.2 x
      10(-4)m in sunflower exudate. 7.3 x 10(-4)m in soybean, 9.4 x 10(-4)m in
      cucumber, and 1.8 x 10(-4)m in tomato. Some of these values represent a doubling
      or tripling of citrate when compared to the lowest ones obtained. High Fe
      depressed the citrate content of exudate in some cases.As iron was raised in the
      nutrient, the increases of iron in the exudate were proportionately greater than
      those of citrate. The highest Fe treatments led to exaggerated uptake of iron by
      sunflower. In some cases iron was translocated in molar excess of citrate. A time
      response experiment with tomato showed a rapid flooding of iron into the roots
      but a relatively slow release of iron into xylem exudate.Similar electrophoretic
      patterns of iron were obtained despite changes in citrate and iron with time.
      Exudates from sunflower, cucumber, and tomato gave iron concentrations in the
      position of iron-citrate.

PMID- 16656283
TI  - Variation of nicotinamide adenine dinucleotide phosphate level in bean hypocotyls
      in relation to o(2) concentration.
AB  - Slices of hypocotyls from 3-day-old seedlings of Vigna sesquipedalis (L.)
      Fruwirth in the germination stage were incubated under various gaseous
      conditions. The NADP+NADPH level in the hypocotyl slices changed with the oxygen
      tension. A high NADP+NADPH level was observed under aerobic conditions and a low
      NADP+NADPH level under anaerobic conditions.The 100 x NADH/NAD+NADH ratio
      increased greatly under anaerobic conditions. In general a low NADP + NADPH level
      corresponded with a high 100 x NADH/NAD+NADH ratio. On the basis of the results
      given in the following paper, it was discussed that the slowness of NADH
      oxidation in hypocotyl tissue due to anaerobic conditions results in the
      inhibition of NADP formation.The variation of the NADP+NADPH level was considered
      to produce a modification of the carbohydrate metabolism.The NADP+NADPH level in
      E. coli cells suspended in glucose solution also changed with the oxygen tension.

PMID- 16656284
TI  - NAD Kinase in Higher Plants.
AB  - NAD kinase was exclusively found in the soluble portion of the cell components.
      The enzyme was purified about 100-fold from sucrose extracts of spinach
      leaves.Plant NAD kinase catalyzes formation of NADP from NAD, ATP, and Mg(++),
      but scarcely any formation of NADPH from NADH. NADH was a very potent competitive
      inhibitor of NAD phosphorylation by plant NAD kinase. The K(i) was 1.0 x 10(
      4)m.The concentration of Mg(++) required to produce maximal activity was 10(-2)m.
      Co(++) or Mn(++) could replace Mg(++) in the system.The pH optimum was 6.8. The
      K(m) for NAD was 2.0 x 10(-3)m and that for ATP was 1.1 x 10(-3)m. No convincing
      demonstration of the reversibility of the reaction was obtained.It was inferred
      from above properties of the enzyme that NADP formation ceases in plant tissues
      in which reduced NAD is accumulated, or in anaerobic tissues.

PMID- 16656285
TI  - Effect of salts and electron transport on the conformation of isolated
      chloroplasts. I. Light-scattering and volume changes.
AB  - Whole chloroplasts isolated from the leaves of spinach (Spinacia oleracea L.)
      exhibit 2 types of conformational change during electron transport. Amine
      uncoupled chloroplasts swell and atebrin-uncoupled chloroplasts shrink.
      Chloroplasts uncoupled by carbonylcyanide phenylhydrazones and by treatment with
      ethylenediamine tetraacetic acid do not change their volumes or light-scattering
      properties during electron transport. Phosphorylating chloroplasts shrink only
      slightly.The rate and extent of the conformational change parallel the rate of
      electron transport; both the decrease in turbidity with methylamine and the
      increase in turbidity with atebrin are rougly proportional to the Hill reaction
      rate. Consequently the great volume and light-scattering changes which occur in
      the presence of these uncouplers can be attributed, in part, to the very high
      rates of uncoupled electron transport. However, for a given rate of electron
      transport the atebrin-induced scattering increase is very much greater than the
      increase observed during photophosphorylation.When uncouplers are combined, the
      carbonylcyanide phenylhydrazone effect (no change) supercedes both the
      methylamine effect (swelling) and the atebrin effect (shrinking). The methylamine
      effect supercedes the atebrin (shrinking) and ethylenediamine tetracetic acid (no
      change) effects. The atebrin effect supercedes the ethylenediamine tetraacetic
      acid effect. A similar hierarchy of effects is observed with regard to the rate
      of the uncoupled electron transport.These light-scattering changes of whole
      chloroplasts reflect similar changes which occur in very small digitonin
      particles of chloroplasts. Therefore one must look among chloroplast
      substructures for the basic mechanism of swelling and shrinking.Many salts
      (including methylamine hydrochloride) cause the chloroplasts to shrink. This
      phenomenon is not osmotic since comparable osmolarities of sucrose are without
      effect. Magnesium chloride and calcium chloride are most effective but all salts
      tested gave major volume decrease when less than 0.05 m. The salt-shrunken
      chloroplasts show greater light-scattering changes during electron transport than
      do low-salt chloroplasts.

PMID- 16656286
TI  - Effect of Salts and Electron Transport on the Conformation of Isolated
      Chloroplasts. II. Electron Microscopy.
AB  - Spinach chloroplasts isolated in media containing salts and the rare chloroplasts
      which are still within their envelopes alike retain grana similar to those seen
      in chloroplasts in situ.Chloroplasts isolated in low-salt media lose their grana
      without losing any chlorophyll. These grana-free chloroplasts are considerably
      swollen and consist almost entirely of continuous sheets of paired-membrane
      structures. These double structures, the lamellae, are only loosely held
      together, primarily at the edges, by tenuous material which does not react with
      permanganate.Addition of salts (methylamine hydrochloride, NaCl, MgCl(2)) to the
      grana-free low-salt chloroplasts provide strong interlamellar attractions. These
      attractions result in a stacking of the lamellae which is sometimes almost random
      but sometimes results in regular structures indistinguishable from the original
      grana.The phosphorylation-uncoupler atebrin causes further swelling of the
      chloroplasts in the absence of electron transport by increasing the space between
      the paired membranes of the lamellae.The rapid electron transport (Hill reaction)
      made possible by atebrin-uncoupling is associated with a great decrease in
      chloroplast volume. This decrease results from a collapsing together of the
      widely separated lamellar membrane pairs. The pairs approach each other so
      closely that they usually appear as a single membrane when viewed with the
      electron microscope. The much slower electron transport which occurs in the
      absence of uncouplers is associated with a similar but smaller decrease in the
      space between the lamellar membrane pairs.Chloroplasts swell during the rapid
      electron transport made possible by the phosphorylation-uncoupler methylamine.
      This swelling is accompanied by a degree of membrane distortion which precludes
      an interpretation of the mechanism. As with atebrin-faciliated electron
      transport, obviously paired membranes disappear but it is not yet clear whether
      this is by association or dissociation of the pairs.

PMID- 16656287
TI  - RNA composition in cotton.
AB  - Nucleotide compositions of soluble (sRNA), whole-cell, and in one instance
      particulate and nonparticulate, RNA of embryos, cotyledons (dark and light
      grown), leaves, stems, and roots of Gossypium hirsutum were compared. Evidence of
      substantial differences in the overall compositions of the RNAs was not obtained.
      However, a tendency for some plant parts to differ, particularly in sRNA
      composition, and that of the cotyledons (including particulate and nonparticulate
      RNA) to change during the formation of chlorophyll, was indicated by small but
      statistically significant shifts in certain nucleotide components.

PMID- 16656288
TI  - Prediction of growth rate at different light levels from measured photosynthesis
      and respiration rates.
AB  - Light integrators with a linear response are not suitable for measuring the light
      climates of plants because plants are not linear integrators. It should be
      possible to make a quantitative allowance for this nonlinearity by using the
      CO(2) uptake curve of the plant. To test this, we have subjected white clover
      plants to different levels of constant light, comparing the rate of increase of
      total dry matter with the net rate of uptake of CO(2) per day. Temperature,
      humidity, daylength and nutrient supply were kept constant. The growth rate
      calculated from CO(2) uptake agreed well with the observed rate over the light
      levels tested (3.7-88 w.m(-2), 0.4-0.7 micron: 1 w.m(-2) = 10(3) erg . sec(-1)
      cm(-2)). All plants put on weight over the few days of the experiment, even those
      placed at light levels below their compensation point. The plants adapted their
      respiration rates to be a constant proportion of their growth rates. Most of the
      adaptation occurred within 24 hours of the light change. The adaptation of
      respiration has implications for models of light/growth relations in plant
      communities, almost all of which assume that respiration is proportional to leaf
      area and independent of growth rate or light level. The only model which does not
      is that of de Wit, and this gave good agreement with our results.

PMID- 16656289
TI  - Purification and Properties of Urease Derived from Hydrated Seeds of Jack Bean,
      Canavalia ensiformis (L) DC.
AB  - Urease from jack bean meal and hydrated seeds has been obtained in 25 to 33%
      yield with specific activity in the range of 1000 to 1070 units/mg protein. A
      purification of 100 to 130-fold was achieved from meal and fully soaked seeds.
      Use of beta-mercaptoethanol and EDTA was found essential to obtain this high
      yield and purity. Amino acid analysis showed all 18 amino acids commonly found in
      proteins. Electrophoresis of urease from soaked seeds (specific activity: 1025
      units/mg protein) on a starch-gel block showed 2 peaks. Upon ultracentrifugation
      of urease samples having a low specific activity (less than 25% pure), the major
      portion of the urease was probably present in a peak having a sedimentation value
      of 11 to 12. With relatively pure samples (55-100% pure). S values in the range
      of 18 to 20 and 24 to 26 were obtained. Usually the purest samples of urease
      tested without any prior storage lacked the 24 to 26 S peak or the higher
      polymeric forms. The percentage areas under none of the ultracentrifuge peaks
      corresponded to the percentage purity of the sample analyzed. It is argued that
      the physical state of urease in the cell when associated with other seed proteins
      is as yet uncertain. In crude extracts, a portion of urease exists in a 12 S form
      but so far data on its origin and specific activity in relation to other species
      of urease are not available.

PMID- 16656290
TI  - Free amino Acid contents of stem and phylloxera gall tissue cultures of grape.
AB  - Free amino acid constituents were determined of grape stem and Phylloxera leaf
      gall callus in tissue culture. Fast, medium and slow growing single cell clones
      of, respectively, stem and gall origins were grown on a mineral salt-sucrose
      medium supplemented with coconut milk and alpha-naphthaleneacetic acid. Stem and
      gall clones showed qualitative similarities and quantitative variations in the
      amino acids and nitrogenous constituents. Nineteen amino acids, glucosamine,
      ethanolamine, sarcosine, methionine sulfoxides and ammonia were identified. Two
      free polypeptides accounted for over 30% of the amino compounds in the stem and
      gall callus tissues which were not found in the intact plant parts. Stem clones
      of different growth rates grown on agar showed generally an excess of amino acid
      constituents over gall tissues of similar growth rates, except for the free
      polypeptides. Fast growing stem clones grown on agar medium contained lower
      amounts of certain amino acids than the fast growing gall clones, but when grown
      in liquid medium they contained higher amounts of these acids than the gall
      clones. The total and nonsoluble nitrogen of stem clones were higher than in the
      gall clones. Tissue cultures differed from the original plant parts with respect
      to their free polypeptides and high amino acid contents.

PMID- 16656291
TI  - Auxin stimulation of ethylene evolution.
AB  - The stimulation of ethylene production from seedling tissue of Phascolus
      vulgaris, Helianthus annuus and Zea mays by growth regulators was inhibited by
      actinomycin D and puromycin and to a lesser extent by 2-thiouracil and p
      fluorophenylalanine. It is concluded that the mechanism of action of growth
      regulators on the enhancement of ethylene production is the formation of enzymes
      involved in ethylene biogenesis.

PMID- 16656292
TI  - Relationships between phytochrome state and photosensitive growth of Avena
      coleoptile segments.
AB  - Using various photostationary state light sources to obtain reproducible
      phytochrome conversion of from 5 to 88% P(FR), assayed by 2 wavelength in vivo
      spectrophotometry, relationships between initial percent P(FR) and elongation of
      apical Avena coleoptile segments over the succeeding 20 hours in darkness were
      studied. With material grown in total darkness, all P(FR) levels promote
      elongation, and maximal promotion requires roughly 50% P(FR). The promotion
      caused by an initial 5 minute red (88% P(FR)) treatment at hour 0 is partially
      reversible at hour 5 by sources forming less than 48% P(FR), but totally
      irreversible at hour 8, though less than 50% of the growth has been accomplished
      by this time. Direct photometric assays at hour 5 indicate a phytochrome state of
      roughly 45% P(FR), consistent with the reversal data. At hour 8, however, 11 to
      22% of the phytochrome still assays as P(FR), an inconsistency suggesting simply
      that the elongation process has proceeded beyond photochemical control. Thus, in
      contrast with results previously reported for Pisum and Phaseolus, there is no
      contradiction between photometric and physiological assays of phytochrome state
      in Avena coleoptile segments.Attempts to expand this study by using segments from
      seedlings pretreated with red light showed that such pretreatment as little as 1
      to 2 hours before drastically reduces subsequent elongation and photoresponse on
      the medium employed. This decline in growth potential can be halted at any time
      before its completion by either excision of the segment or far-red treatment of
      the intact seedling.

PMID- 16656293
TI  - Effects of decenylsuccinic Acid on the permeability and growth of bean roots.
AB  - Decenylsuccinic acid (DSA) at 10(-3)m has been reported to increase the
      permeability of bean root systems to water without seriously injuring the plants.
      We have confirmed the increase in permeability at 10(-3)m, but have found that
      10(-4)m DSA reduces the permeability. Both concentrations cause leakage of salts
      from the roots and cessation of root pressure exudation. The roots of intact bean
      plants are killed by 1 hour's immersion in 10(-3)m DSA, but the plants may
      survive by producing new roots. Up to 4 hours in 10(-4)m DSA causes only
      temporary cessation of growth. Comparisons are made between the effects of DSA
      and some metabolic inhibitors. It is suggested that DSA is acting as a metabolic
      inhibitor, and that increase in water permeability is the result of injury to the
      roots. Experiments with 3 other species indicated variations in response to 10(
      3)m DSA. These could be largely attributed to differences in susceptibility to
      injury.

PMID- 16656294
TI  - A mechanism for the leaching of calcium from foliage.
AB  - Young bean plants (Phaseolus vulgaris) containing root-absorbed (45)Ca and (86)Rb
      were leached to determine the pathway and mechanism of cation loss by leaching.
      Calcium is leached from the exchangeable calcium fraction within the plant by a
      process of ion exchange and diffusion involving exchange sites both within the
      leaf and on the leaf surface. Leaching of cations is primarily a passive process,
      although some metabolites may be deposited upon leaf surfaces by active
      processes. The exchange and diffusion explanation is compatible with current
      theories of ion uptake and translocation and explains the results of numerous
      experiments on leaching reported in the literature.

PMID- 16656295
TI  - Stress and hormone interrelationship in branch growth.
AB  - Calculated stress patterns in lateral branches place the locations of maximum
      flexural stresses at the same places as the maximum concentrations of growth
      hormones. The gradients of stress and hormone concentration also have
      similarity.In branch epinasty and negative geotropism of branches, the directions
      of the stress vectors correlate with the imbalance of auxin in the upper and
      lower portions of the branches.

PMID- 16656296
TI  - Changes during recovery from sodium deficiency in atriplex.
AB  - Although the concentration of sodium in leaves of Atriplex plants increased
      rapidly after receiving sodium, no growth response was detectable for about 6
      days. It was found that respiration rate increased to its maximum within 3 days.
      Chlorophyll content also increased from an early stage, whereas the
      concentrations of sugars and starch did not increase, and ratios of soluble to
      total nitrogen did not decrease until later.The respiratory response appears to
      be specific to sodium as different salts of sodium caused similar responses, and
      no other univalent cation substituted for sodium. In addition, both growth
      response and respiration rate tended towards their maxima with the same
      concentration of applied sodium. The rate of anaerobic CO(2) production increased
      when sodium was fed to leaves, suggesting that the effect of sodium is in the
      glycolytic sequence.

PMID- 16656297
TI  - Variations in endogenous gibberellins in developing bean seeds I. Occurrence of
      neutral and acidic substances.
AB  - Activities of separated and chromatographed substances in the nonacidic, acidic
      ethyl acetate and acidic butanol fractions from bean seeds, Phaseolus vulgaris
      L., cv. Bountiful and Kentucky Wonder, were measured in the Progress No. 9 dwarf
      pea bioassay grown under red light. Activity in the nonacidic fraction was shown
      to be attributable only to neutral substances and was free of acidic gibberellin
      like substances. As the seed matures, neutral substances and one of the acidic
      butanol-soluble substances (B-I) increase in activity. The acidic ethyl acetate
      substances and butanol-soluble substance (B-II) initially increase and then
      almost disappear.

PMID- 16656298
TI  - Variations in Endogenous Gibberellins in Developing Bean Seeds II. Changes
      Induced in Acidic and Neutral Fractions by GA(1).
AB  - Immature (8-mm), medium mature (11-mm), and mature green (16- and 17-mm) bean
      seeds (Phaseolus vulgaris L. cv. Kentucky Wonder and Bountiful) were incubated in
      gibberellin A(1) solutions for 24 hours at 20 degrees . Extracts from the seeds
      were separated into nonacidic, acidic ethyl acetate, and acidic butanol
      fractions. These were chromatographed. The eluates of the chromatograms were
      tested on Progress No. 9 dwarf peas grown under red light. The level of neutral
      gibberellin-like substances remained unchanged in immature seed, but they
      increased markedly in mature green seeds. Coincident with increased levels of the
      neutral substances, there were significant decreases in acidic ethyl acetate
      soluble gibberellin-like substances, including applied GA(1), and in 1 acidic
      butanol-soluble gibberellin-like substance. Seed incubation in GA(1) brought
      about increased activity of substance B-II in immature and medium mature seeds.
      The level of butanol-soluble gibberellin-like substance B-I in seeds of any size
      was not affected by incubation in GA(1). Considering the marked increases in
      activity induced in the neutral fraction and the decreases in activity of certain
      eluates from the chromatograms of the acidic fractions, it was concluded that the
      neutral fraction may serve as a reserve form of gibberellins in the dry seed. The
      acidic ethyl acetate substances and substance B-II may be required for normal
      development of the bean seed.

PMID- 16656299
TI  - Requirement for plastoquinone a in the hill reaction of isolated chloroplasts.
AB  - In order to avoid the problem of an uncoupling effect in stimulation of potential
      Hill reaction activity during extraction with heptane. Hill reaction activity was
      measured with uncoupled spinach chloroplasts. The reactions were also run under
      aerobic conditions. Under these conditions a correction for a 3-(p-chlorophenyl)
      1, 1-dimethylurea insensitive, photostimulated O(2) uptake reaction is necessary,
      especially with extracted chloroplasts. The reaction displayed proper Hill
      reaction stoichiometry in untreated and restored systems if these corrections
      were made. Plastoquinone A always restored some activity to the extracted
      chloroplasts but never restored activity to the original level. Additional
      activity could be restored by the crude extract. It appears that there is a clear
      requirement for plastoquinone A in the Hill reaction but the restoration of
      maximum activity depends upon additional factors. The variability of response to
      plastoquinone A which has been reported in various laboratories may be determined
      by the degree of extraction of the other materials.

PMID- 16656300
TI  - Xylem sap flow as affected by metabolic inhibitors and girdling.
AB  - The flow of sap in Populus tremuloides was studied by the thermoelectric method
      immediately prior to and at several periods of time after radical girdling.
      Similarly, the flow of sap in Betula papyrifera was studied before and after
      girdling or injection with metabolic inhibitors or a filtrate of a culture of
      Ceratocystis ulmi.None of the treatments caused any significant change in the
      speed at which the sap flowed. However, the rate at which the temperature rose at
      the upper (downstream) thermocouple decreased significantly in girdled trees and
      in most trees treated with metabolic inhibitors. That decrease was first noticed
      4 days after poisoning with 0.1 m mercuric chloride, and 1 day after poisoning
      with either 0.01 m picric acid or a culture filtrate of Ceratocystis ulmi. A 0.05
      m trichloroacetic acid solution caused a decrease in the rate of temperature rise
      about 2 hours after the tree was injected. The rate of temperature rise returned
      to normal the next day after the injection with trichloroacetic but again showed
      a decrease after 42 days.Increases in the rate of heat rise were noted the day
      after the birch trees were girdled, and all girdled trees showed a significant
      decrease in the rate of heat rise sometime after they were girdled. Many of the
      girdled trees showed no sap flow or even an apparent downward flow of xylem sap
      sometime after girdling.Laboratory experiments indicated that the blocking of the
      vessels by air emboli would result in a significant change in the rate of
      temperature rise, not accompanied by a significant change in the speed at which
      the sap flowed. Since air emboli caused similar results to those actually
      experienced in the field, the data are interpreted as the result of blocked or
      nonfunctional vessels.All of the data agree with that of earlier workers.
      Cessation of upward flow occurs only in girdled trees after rather long periods
      of time. It is suggested that cessation could be caused by tyloses and air
      emboli. All of the data are also in agreement with the passive theories of sap
      ascent. However, the trichloroacetic acid experiments suggest the existence of a
      repair mechanism or a second means of sap movement.

PMID- 16656301
TI  - Cytokinin activation of thiamine biosynthesis in tobacco callus cultures.
AB  - Bioassays of tissue extracts show that high (500-1000 mug/liter) kinetin
      concentrations which permit growth of tobacco callus cultures on media without
      added thiamine activate the biosynthesis of this vitamin by the tissues. Although
      the tissue concentration of thiamine may fall appreciably, it is maintained at a
      level adequate for survival and slow growth of the cultures, and there is a large
      net increase in total thiamine content per culture with time. In the second and
      subsequent passages of tissue on a thiamine free medium, growth is obtained only
      when high kinetin concentrations are maintained. Effective inhibition of growth
      by antithiamines suggests that thiamine is utilized by the high-kinetin tissue.In
      the presence of low (30-100 mug/liter) kinetin concentrations, which would be
      optimal for growth in the presence of thiamine, growth only occurs early in the
      first passage of tissue from a medium with the vitamin to one without it. The
      thiamine concentration in the tissues falls to low levels, and no net
      biosynthesis is apparent. The tissues turn dark and die after 2 to 3 weeks. In
      contrast with this, in the absence of both added thiamine and kinetin no
      appreciable growth occurs, but the tissues keep their normal appearance, retain
      their thiamine content, and may stay alive for several weeks.

PMID- 16656302
TI  - Metabolism of red beet slices I. Effects of washing.
AB  - The changes in relative participation of pathways of glucose catabolism in red
      beet slices during washing have been examined using specifically (14)C labeled
      glucoses. Washing of these slices brings about an increase in participation of
      the pentose phosphate pathway. The composition of the washing medium influences
      slightly the extent of change in pathway participation. The activity level of
      certain enzymes participating in the initial stages of glucose catabolism has
      been measured in fresh and washed beet slices. Fresh slices which barely
      metabolized gluconate were found to have very little 6-phosphogluconate
      dehydrogenase activity. Washing brings about a dramatic increase in 6
      phosphogluconate dehydrogenase activity and this increase was accompanied by a
      marked increase in the ability of the slices to metabolize gluconate. In red beet
      slices the TPNH generated via pentose phosphate pathway appears to be utilized
      for biosynthetic reductions rather than as respiratory substrate.

PMID- 16656303
TI  - Metabolism of Red Beet Slices II. Effects of Aging.
AB  - The rate of respiration of red beet slices increased 3- to 4-fold when the slices
      were aged in a moist atmosphere for 18 to 24 hours. The respiration of fresh
      slices was severely inhibited by 8 x 10(-5)m HCN but as slices aged the
      sensitivity of respiration to HCN fell rapidly. The presence of HCN stimulated
      the respiration of slices after 8 to 12 hours of aging.The relative participation
      of the pentose phosphate pathway in the glucose catabolism increased very little,
      if any, during aging of slices prepared from beets in the growing phase although
      the total metabolic rate seems to be greatly increased. However, data obtained
      from slices prepared from dormant beets indicated a possible increase in pentose
      phosphate pathway participation in glucose catabolism upon aging. The activity of
      6-phosphogluconate dehydrogenase increased very markedly during aging and a
      corresponding marked increase in the ability of the tissue to metabolize
      gluconate was observed. It is concluded that to associate the aging process of
      storage tissue slices with a specific increase in a particular pathway is not
      justifiable.

PMID- 16656304
TI  - Polarity of IAA Effect on Sieve-Tube and Xylem Regeneration in Coleus and Tomato
      Stems.
AB  - A technique is described for the processing of regenerated xylem and sieve tubes
      from the same wound area for microscopic and quantitative comparison.Regeneration
      was examined in internodes of 2 developmental stages in Coleus: internode 2,
      elongating, characteristic of primary growth; and internode 5, non-elongating,
      characteristic of secondary growth.Transport of indoleacetic acid (IAA) in
      excised number 5 internodes of Coleus is strictly polar, in a basipetal
      direction, judging by a regeneration bioassay involving both sieve tube strands
      and xylem cells. Similar results were obtained with tomato.If isolated number 5
      Coleus internodes are not treated with hormone, they regenerate no xylem cells
      and a small number of sieve tube strands. With increasing concentrations of IAA
      added apically, the number of regenerated sieve tube strands (and, with higher
      concentrations, of xylem cells) increases progressively up to 1% IAA, the highest
      concentration applied.Internode 2 of Coleus regenerates fewer xylem cells or
      sieve tube strands than internode 5, whether on the otherwise intact plant or
      with a given concentration of IAA added apically. The amount of regenerated xylem
      increases with added apical IAA, except that the highest concentration gives no
      further increase. The number of xylem cells regenerated in intact plants occurs
      at the same interpolated IAA concentration as in number 5 internodes. No
      concentration of IAA tried provided replacement of intact number of sieve tube
      strands in internode 2.IAA can exert a regenerative stimulus on both xylem and
      sieve tubes in the area immediately adjacent to the site of its application.

PMID- 16656305
TI  - Distribution of the Products of Photosynthesis between Powdery Mildew and Barley.
AB  - The photosynthetic assimilation of (14)CO(2) has been studied in healthy and
      mildew-infected barley. The parasite was separated from the host by removing the
      mycelium with a camel's hair brush. The ethanol soluble metabolites of the
      parasite, infected host and healthy host were extracted, separated by paper
      chromatography and individually identified. From this work it appears that there
      is a rapid movement of label from host to parasite mainly in the form of sucrose
      which is then quickly metabolized into many compounds. The majority is converted
      into mannitol, and lesser amounts are converted into trehalose, arabitol,
      aspartic acid, and glutamic acid. In conidia the major carbon reserve is arabitol
      instead of mannitol, with lesser amounts of trehalose and mannitol.Photosynthetic
      uptake of (14)CO(2) by the complex decreases steadily after inoculation as
      compared with healthy leaves. However, the ethanol soluble metabolites of the
      infected host tissue differ only slightly from those of healthy host tissue. The
      major differences are a slight decrease in the amount of sucrose and increases in
      malic acid and serine.

PMID- 16656306
TI  - Extraction of nucleic acids from lyophilized plant material.
AB  - Four methods for extracting nucleic acids from lyophilized cotton (Gossypium
      hirsutum L. cv. Stoneville 62) leaves and roots were compared. They were based on
      the use of: (I) HC10(4); (II) KOH; (III) a mixture of 90% phenol, Tris
      (hydroxymethyl) aminomethane buffer, and sodium lauryl sulfate; and (IV) NaCl.
      (I) extracted large amounts of RNA but little DNA and extracted much carbohydrate
      and protein contaminants. (II) gave a good yield of both RNA and DNA but
      extracted such large amounts of contaminating material that purification of RNA
      on an anion exchange column was necessary. (III) extracted only part of the RNA
      and practically no DNA, but extracted contaminating materials. (IV) resulted in
      high yields of both RNA and DNA when modified to omit preliminary acid extraction
      of impurities. The use of cold trichloroacetic acid instead of ethanol, to
      precipitate NaCl-extracted nucleic acids, separated the nucleic acids from most
      of the carbohydrate and acid-soluble phosphate contaminants and resulted in good
      agreement among results by ultraviolet absorbance, pentose tests, and phosphate
      analysis. This method also resulted in lower protein contents and better
      ultraviolet absorption spectra than the other methods tested. Nucleic acids were
      extracted from leaves of 14 other species of plants, in addition to cotton, by
      this modified NaCl procedure.

PMID- 16656307
TI  - Plastoquinone B.
AB  - A compound found in spinach and other higher plants previously referred to as R
      263 has now been found to be a breakdown product of plastoquinone B. This
      quinone, PQ B, is found with 8 other quinones in spinach chloroplasts. These 9
      quinones are PQ A, PQ B, PQ C, PQ D (7, 8, 15) Vitamin K(1) (10, 12), an unknown
      naphthoquinone (13) and alpha-, beta- and gamma-tocopherylquinones (7, 12). An
      improved method for purification of plastoquinone B is described. Previous
      confusion of this compound with other quinoid material on silica gel is described
      and corrected R(F) values are given. The activity of PQ B is similar to the
      activity of PQ C in restoration studies of the photo-reduction of ferricyanide
      and indophenol.

PMID- 16656308
TI  - Permeability Characteristics and Amino Acid Incorporation during Senescence
      (Ripening) of Banana Tissue.
AB  - Changes in free space of banana tissue during ripening were measured using
      radioisotopes. Free space increased significantly about 44 hours before the onset
      of, and rose exponentially during the respiratory climacteric. The increase in
      free space indicates a progressive increase in the proportion of cells which
      becomes completely permeable to solutes in the ambient solution by simple
      diffusion. At the respiratory peak the tissue was essentially 100% free space to
      mannitol, sucrose, fructose and chloride.The capacity for active uptake of
      solutes declined about one day before the onset of the respiratory rise and fell
      to a very low level by the respiratory peak.There was no change in the level of
      protein or amino acids during ripening. Assays of tissue sections before and
      after washing indicated an increased rate of leakage of amino acids during
      ripening.Studies of incorporation of 3 concentrations of (14)C-labeled leucine
      and phenylalanine indicated marked changes in the size and specific activity of
      the amino acid pool at the site of protein synthesis just prior to and during the
      climacteric rise, due to a diffusive mixing of the labeled substrate with the
      previously sequestered endogenous, unlabeled pool of substrate. The use of a high
      concentration of exogenous substrate (above saturation for uptake) resulted in an
      apparent constant specific activity of the metabolic pool through the ripening
      period. Data from these studies indicated a decline in amino acid incorporation
      during the climacteric.It was concluded that the initiation of permeability
      changes marks the onset of senescence in banana. The causative relations between
      alterations in permeability, the respiratory rise and other chemical changes
      attending fruit ripening are discussed.

PMID- 16656309
TI  - Compartmentation of organic acids in corn roots I. Differential labeling of 2
      malate pools.
AB  - Bicarbonate-(14)C and acetate-(3)H were simultaneously provided to corn roots to
      give 2 isotopic forms of malate in the tissue, malate-(14)C produced by dark
      fixation reactions and malate-(3)H produced by reactions of the tricarboxylic
      acid cycle. Following a short pulse of exposure to the isotopes, the
      dissimilation of both isotopic forms of malic acid was followed. The rate of
      utilization of malate-(3)H was much faster than that of malate-(14)C.These
      results are interpreted as showing that the malate produced from (14)CO(2) is in
      a pool physically separated from that in the tricarboxylic acid cycle. The
      introduction of the 2 isotopes through distinct metabolic pathways produced the
      differential labeling of 2 distinct pools of malate.

PMID- 16656310
TI  - Compartmentation of Organic Acids in Corn Roots II. The Cytoplasmic Pool of Malic
      Acid.
AB  - The major conclusion drawn was that malate generated in corn roots during a 15
      minute period of CO(2) fixation and malate introduced into the tissue during a
      similar period from the bathing medium share a common extramitochondrial
      compartment, the cytoplasmic pool. The utilization of these 2 forms of malate is
      normally much slower than that of malate generated in the mitochondria by the
      tricarboxylic acid cycle. By lowering the pH of the medium or treating the tissue
      with malonate or 2,4-dinitrophenol, similar increases in the rates of utilization
      of both forms of cytoplasmic malate were brought about. Changes in (A) the demand
      for acetyl acceptors in the mitochondria and (B) mitochondrial permeability were
      invoked to account for the increased utilization of the cytoplasmic malate under
      the various experimental treatments.

PMID- 16656311
TI  - Effect of manganese toxicity on the indoleacetic Acid oxidase system of cotton.
AB  - The effect of substrate manganese on tissue manganese levels and activity of the
      indoleacetic acid (IAA)-oxidase system of cotton (Gossypium hirsutum, L.) was
      investigated. A sand culture technique was used with 1, 3, 9, 27 and 81 mg
      manganese (MnSO(4)) per liter nutrient solution applied in various
      experiments.The following relationships held for both long-term (126 days) and
      short-term (12-14 days) exposures to manganese treatment: A) There was a direct
      relationship between substrate and tissue manganese. B) Only the 81 mg/liter Mn
      plants exhibited severe manganese toxicity symptoms. C) At the toxic level of
      manganese an increased IAA-oxidase activity and decreased IAA-oxidase inhibitor
      activity was observed. There was a direct relationship between degree of enzyme
      response and severity of visible symptoms. D) With the manganese toxicity plants,
      but none of the other treatments, extracts of the young leaves contained as much
      IAA-oxidase activity as extracts of much older leaves. E) Crude extracts from the
      plants grown with 81 mg manganese per liter solution, in contrast to those of
      other treatments, destroyed IAA without addition of MnCl(2) to the assay medium.A
      hypothesis is advanced stating that manganese toxicity symptoms in cotton are
      expressions of auxin deficiency caused by IAA-oxidase activity increased by the
      abnormal tissue levels of manganese.

PMID- 16656312
TI  - Transport of the Auxin 2,4-Dichlorophenoxyacetic Acid Through Absiccion Zones,
      Pulvini, and Petioles of Phaseolus vulgaris.
AB  - Measurements were made of the transport of 2,4-dichlorophenoxyacetic acid-(14)C
      (2,4-D) through segments cut from the region of the distal abscission zone in
      young and old primary leaves of Phaseolus vulgaris L. When old leaves were used
      basipetal transport of 2,4-D in segments including pulvinar tissue, abscission
      zone, and petiolar tissue was much less than in wholly petiolar segments. In both
      young and old plants, segments consisting entirely of pulvinar tissue transported
      2,4-D basipetally at a velocity about half that in petiolar tissue. At both ages
      the flux of 2,4-D through pulvinar tissue was less than that through petiolar
      tissue. In segments from old leaves the flux through pulvinar tissue was much
      less than in young plants; the flux through petiolar tissue changed little with
      age. There was no change with age in the velocity of basipetal transport. The
      distribution of (14)C along segments including the abscission zone showed no
      marked discontinuity. It was concluded that the pulvinus limited the basipetal
      movement of 2,4-D through segments from old leaves which included both pulvinar
      and petiolar tissue, but there was no evidence that the abscission zone itself
      was a barrier to auxin transport.

PMID- 16656314
TI  - Particulate cytochromes of mung bean seedlings.
AB  - Efforts have been made to solubilize cytochrome components from particulate
      fractions of etiolated mung bean seedlings. Low temperature spectrophotometry
      reveals that the cytochrome composition of mitochondria isolated from whole
      seedlings is the same as that reported by Bonner for mung bean hypocotyls. On the
      basis of the identity in position of the alpha-bands in low temperature
      difference spectra for mitochondria, for a partially purified haemoprotein from
      mitochondria, and for purified cytochrome b-555, it is suggested that cytochrome
      b-555 is an intrinsic component of mung bean mitochondria. Difference spectra
      show that both the mitochondrial and microsomal fractions contain at least 2 b
      type cytochromes. Cytochrome b-555 is almost certainly present in the microsomes,
      since the low temperature difference spectrum for the cytochrome is identical
      with the spectrum for this particulate fraction.By freezing and thawing mung bean
      mitochondria in 4% cholate and centrifuging, cytochrome oxidase activity can be
      concentrated in the supernatant fraction, although it is not completely
      solubilized. The oxidase is inhibited by high concentrations of cytochrome c. A
      particle-bound cytochrome c can be obtained from mitochondria by digestion with
      snake venom. However, the autoxidizability of the preparation indicates that the
      cytochrome has been solubilized in a modified form. A CO-binding pigment can be
      obtained from mung bean microsomes by digestion with snake venom.

PMID- 16656315
TI  - Maintenance of polarity of auxin movement by basipetal transport.
AB  - The polar, basipetal transport of indoleacetic acid helps to maintain polarity of
      auxin movement in coleoptiles of Avena sativa L. by opposing acropetal diffusion.
      This conclusion is supported by 3 different kinds of experiments. In all 3
      experiments, sections took up (14)C carboxyl-labeled indole-3-acetic acid
      anaerobically, and the distribution of auxin within all sections was similar at
      the end of uptake.[LIST: see text].

PMID- 16656316
TI  - Dark CO(2) Fixation and its Role in the Growth of Plant Tissue.
AB  - Experiments were designed to determine the significance of dark CO(2) fixation in
      excised maize roots, carrot slices and excised tomato roots grown in tissue
      culture. Bicarbonate-(14)C was used to determine the pathway and amounts of CO(2)
      fixation, while leucine-(14)C was used to estimate protein synthesis in tissues
      aerated with various levels of CO(2).Organic acids were labeled from bicarbonate
      (14)C, with malate being the major labeled acid. Only glutamate and aspartate
      were labeled in the amino acid fraction and these 2 amino acids comprised over
      90% of the (14)C label in the ethanol-water insoluble residue.Studies with
      leucine-(14)C as an indicator of protein synthesis in carrot slices and tomato
      roots showed that those tissues aerated with air incorporated 33% more leucine
      (14)C into protein than those aerated with CO(2)-free air. Growth of excised
      tomato roots aerated with air was 50% more than growth of tissue aerated with
      CO(2)-free air. These studies are consistent with the suggestion that dark
      fixation of CO(2) is involved in the growth of plant tissues.

PMID- 16656317
TI  - Effects of calcium deficiency on symbiotic nitrogen fixation.
AB  - The mechanism of the effect of mild calcium deficiency on nitrogen metabolism of
      the symbiotic plant was studied from the distribution of calcium and of nitrogen
      and carbohydrate fractions in plant organs.Nitrogen concentrations of all plant
      organs decreased with calcium deficiency. Addition of either a nitrogen or a
      calcium salt increased nitrogen concentrations. For roots as well as whole plants
      the effects of one salt were largely replaced by the other. These effects
      establish that calcium deficiency decreased the supply of fixed nitrogen from
      nodules to other organs. As weight of nodules was independent of calcium it
      follows that nodular efficiency was impaired.Since nitrogen concentrations of
      nodules decreased rather than increased with calcium deficiency it is suggested
      that calcium deficiency interferes with the rate of reduction of nitrogen in the
      nodule rather than with the export of reduced nitrogen. Distribution of alpha
      amino, amide, and ammonium nitrogen are consistent with this suggestion.Nitrogen
      fixation was not limited by translocation of carbohydrates to nodules as calcium
      deficiency had little effect on the concentration of soluble carbohydrates and
      actually increased the concentration of starch in nodules.Calcium deficiency
      depressed the calcium content of nodules so that nitrogen fixation may have been
      impaired by inadequate calcium for nodular structure or metabolism.

PMID- 16656318
TI  - Amino Acid incorporation by wheat chloroplasts.
AB  - Isolated chloroplasts from wheat leaves incorporate radioactive amino acids into
      protein. Both physiological and biochemical evidence show that contaminating
      bacteria are not responsible for the activity. Activity is best in plastids from
      5-day-old or younger seedlings; a sharp drop usually occurs by day 6 or 7. The
      system requires added adenosine triphosphate, guanosine triphosphate and Mg(++),
      and is inhibited by ribonuclease, puromycin and chloramphenicol. Preliminary
      evidence is presented that polyribosomes are present in the young leaf
      chloroplast fraction. Half of the protein that is formed in a 20-minute
      incubation is released in soluble form.

PMID- 16656319
TI  - Gibberellin-like Substances from the Developing Banana Fruit.
AB  - The occurrence of 2 gibberellin-like substances was demonstrated in the
      developing banana fruit, Musa sapientum, Linn. Chemical and biological evidence
      led to the tentative identification of the 2 compounds as GA(7) and GA(x)
      (previously isolated from citrus fruits). Support for such identification was
      obtained from thin layer chromatography, gradient elution column chromatography,
      spectrofluorometry, the dwarf maize test, and the cucumber hypocotyl test.
      Significance of the GA(x) -designated compound increased since it is believed to
      occur in the fungus Fusarium moniliforme, Sheld. in addition to 2 different
      species of higher plants. It does not resemble any of the known gibberellins as
      far as chromatography is concerned.

PMID- 16656320
TI  - Light-dependent modifications in the metabolic responses of squash seedlings.
AB  - Light-induced modifications in lipoxidase metabolism and chlorophyll formation in
      the cotyledon of squash (Cucurbita moscata) seedlings were determined. The enzyme
      activity decreased as light intensity increased, but chlorophyll continued to
      accumulate long after lipoxidase activity had virtually disappeared. Considering
      the differences in the levels of irradiance required to manifest the optimal
      responses, and also from the results obtained with ultraviolet and red, far-red
      light treatments, any causal relationship between lipoxidase disappearance and
      chlorophyll synthesis was ruled out.The observed light-saturation phase in the
      chlorophyll synthesis, indicated that chlorophyll formation was initially
      controlled by the phytochrome system. No similar saturation stage for the enzyme
      responses was observed.The sensitivity of lipoxidase to prolonged light exposures
      suggested a strong correlation with the known photoreactions presumed to be
      controlled by the high energy reactive-phytochrome system. Lipoxidase metabolism
      is, therefore, suggested as a biochemical index for the photomorphogenic
      reactions similar to the ones induced by the high energy reaction.

PMID- 16656321
TI  - Interrelations between photoperiod, frost hardiness and sulfhydryl groups in
      cabbage.
AB  - Hardening of SD (8 and 12 hrs) and LD (18- and 24-hr photoperiods) cabbage plants
      in stages at temperatures starting with + 5 degrees and ending with - 3 degrees
      led to the following changes:Soluble protein plus nonprotein N showed a net
      increase only in the SD plants. In both SD and LD plants, it decreased to a
      minimum toward the end of the first stage of hardening, increased to a maximum in
      the second stage. The degree of this change was proportional to the photoperiod.
      These changes were mainly due to the proteins.As in previous investigations, SH
      content rose during the first 1 to 2 weeks, but only in the SD plants. This rise
      was primarily due to the protein fraction. After the first 1 to 2 weeks both SD
      and LD plants showed a decrease in SH content, most pronouncedly during the
      second stage of hardening.Nonprotein SH content was very low and decreased during
      hardening in both SD and LD plants. Nonprotein SS increased during the first
      stage of hardening. Total nonprotein SH+2SS rose to a maximum during the first
      stage of hardening, paralleling both osmotic potential and hardiness. During the
      second stage the total decreased, in spite of the rise in hardiness. These
      results held true for both SD and LD plants.These results are all explainable on
      the basis of the SHright harpoon over left harpoonSS theory of frost resistance.

PMID- 16656322
TI  - Stimulations of oxygen uptake by electron transfer inhibitors.
AB  - The stimulation of oxygen uptake induced in avocado tissue slices by amytal,
      azide and cyanide has been studied. The effects of these inhibitors on O(2)
      uptake and on phosphorylation suggest the coexistence of phosphorylating and non
      phosphorylating electron transfer systems in the fruit. The reason for the
      stimulations of O(2) uptake is believed to be the result of an increased supply
      of a limiting cofactor to the phosphorylating sites. The increased availability
      of cofactor per site is due to the inhibition of part of the cytochrome chain and
      the consequent reduction in the number of active phosphorylating sites.

PMID- 16656323
TI  - Biogenesis of mitochondria in germinating peanut cotyledons.
AB  - The increase in respiratory activity in germinating peanut cotyledons has been
      correlated with an actual increase in mitochondria. Using sucrose gradient
      centrifugation, it was shown that succinoxidase activity is associated with a
      well-defined band of cell particulates of uniform density, size and
      ultrastructure. During germination the population of succinoxidase-containing
      particles increases, as shown by enzymatic assay, protein assay and direct
      particle counts with the phase contrast microscope.

PMID- 16656324
TI  - Spore Germination and Carbon Metabolism in Fusarium solani V. Changes in
      Anaerobic Metabolism and Related Enzyme Activities during Development.
AB  - Macroconidia of Fusarium solani f. phascoli have no detectable capacity to
      respire glucose anaerobically; germinated spores and mycelium, on the other hand,
      ferment glucose, although slowly.Extracts of ungerminated spores contain
      hexokinase, phosphohexoisomerase, phosphofructokinase, aldolase, triose phosphate
      dehydrogenase, triose phosphate isomerase, phosphoglyceric kinase, enolase,
      phosphoglyceric mutase, pyruvate kinase, and pyruvate decarboxylase. It follows,
      therefore, that the appearance of fermentative capacity during spore germination
      cannot be ascribed to the de novo synthesis of any of these enzymes.During
      germination and mycelial development the specific activity of all of the enzymes
      named except phosphohexoisomerase and aldolase increases 2- to 8-fold. Specific
      activity of all of the enzymes is substantially higher than the fermentative
      capacity of intact cells, i.e., none is limiting to anaerobic respiration.The
      enzymatic assay data are consistent with a conclusion reached earlier on the
      basis of studies of aerobic glucose metabolism, that the process of germination
      involves an acceleration of pre-existing metabolic systems rather than an
      appearance of new pathways.

PMID- 16656325
TI  - Requirement of ginkgo pollen-derived tissue cultures for boron and effects of
      boron deficiency.
AB  - Ginkgo biloba L. pollen-derived tissue, which is made up of small, friable masses
      of homogeneous parenchymatous cells, was shown to require boron in the culture
      medium. If no boron is supplied, growth soon stops. Growth responses to additions
      of boron were observed up to an optimum level of 0.1 mg of boron per
      liter.Histological examination and chemical analyses showed 2 general effects of
      boron deficiency: (1) a reduced rate of cell division, with no significant effect
      on cell size, and (2) some alteration in composition of the cell walls. With the
      exception of a reduction in fructose, the concentration of soluble and of readily
      hydrolyzable carbohydrates, and the concentration of protein in the tissue, were
      not affected by boron deficiency.

PMID- 16656326
TI  - Abscission as a mobilization phenomenon.
AB  - The possibility that leaf abscission might involve a mobilization phenomenon
      leading to a localized cellular senescence was examined by following dry weight
      changes, chlorophyll content, and protein levels in proximal and distal tissue of
      excised pieces of bean petioles from Phaseolus vulgaris L. var. Red Kidney.
      Nucleic acid levels were determined as were phosphate pool sizes in conjunction
      with (32)P labeling patterns. Each of these parameters indicated a mobilization
      into the tissues proximal to the zone of cellular separation at the expense of
      the distal tissues, suggesting that mobilization and the consequent development
      of cellular senescence provide a component in the process of bean leaf
      abscission.

PMID- 16656327
TI  - Hormonal Relations in the Phototropic Response IV. Light-Induced Changes of
      Endogenous Auxins in the Coleoptile.
AB  - Beside indoleacetic acid (IAA), 3 auxins were found by chromatographic resolution
      of acidic fractions of Avena and Zea coleoptile tips. One of these auxins,
      designated P, occurred at levels of activity approaching those of IAA. The other
      2 auxins, termed F and M, occurred at lower levels of activity. When the auxins
      of the excised coleoptile tips were isolated immediately after equilateral or
      unilateral irradiation with blue light at first positive energies, the ratio of
      IAA to the other auxins increases. This rise is the result of a decrease in P and
      F, and probably an increase in IAA. Light did not affect materially the total
      auxin content. It is suggested that P and F might be associated with the
      basipetal transport inequalities of IAA in phototropism.P has been partially
      characterized. Its R(F) on chromatograms developed in ammoniacal isopropanol is
      about 0.65. It is converted to IAA in vitro by heat. The ultraviolet absorption
      spectrum of chromatographically resolved P also suggests an indolyl complex. P is
      not readily transported basipetally, and the slope of its relative concentration
      response curve (Avena section test) is lower than that of IAA. P does not appear
      to be any of the chemically characterized native auxins.

PMID- 16656328
TI  - Acid phosphatase activity of normal and tumor tissue of tobacco grown in vitro
      and in vivo.
AB  - Tissue cultures of Nicotiana labacum consisting of green, albino and habituated
      (normal origin) and teratoma (tomorous origin) were grown under asceptic
      conditions for 6 to 8 weeks and their extracts were analyzed for phosphatase
      activity. Comparative enzyme analyses were also made on crude stem extracts of
      greenhouse-grown normal and tumor tissues of Nicotiana tabacum (var. Wisconsin)
      and a hybrid (N. glauca x N. langsdorffii).All the crude extracts showed acid
      phosphatase activity with a pH optimum at 5.8 to 6.0. The total protein content
      and enzyme acivity of teratoma tissue (tumor) was higher than that of green,
      albino or habituated tissue (normal). Similar increased levels were seen in tumor
      tissue grown in greenhouse in comparison with greenhouse-grown normal tissues.
      The crude extracts of each of the tissues did not exhibit any qualitative
      difference in specificity with the 5 different substrates tested; however,
      differences in the level of activity was observed.The effect of 4 different
      culture media was tested on the growth, protein content and acid phosphatase
      activity of habituated tobacco in tissue culture. Tissues growing in medium
      containing high salt concentrations showed higher activities than tissues grown
      in a basal control medium. From the results, it is suggested that although many
      factors like auxin and other growth factors can influence growth of habituated
      tobacco tissue, they need not necessarily affect this specific enzyme activity.

PMID- 16656329
TI  - Role of leaves in phototropism.
AB  - Experiments with green seedlings of sunflower (Helianthus annuns L.) indicate the
      existence of a phototropic mechanism which involves the leaves or cotyledons, and
      which can produce an asymmetry of auxin content without the involvement of
      lateral auxin transport, the classic explanation of phototropism in etiolated
      seedlings. The basic lines of evidence for the leaf-mediated tropism are: 1)
      darkening of one cotyledon will cause curvature of the stem toward the lighted
      cotyledon: 2) the darkened cotyledon sustains an enhanced growth rate in the stem
      below it: 3) conversely, light suppresses the growth-stimulating effects of a
      single cotyledon: and 4) more diffusible auxin is obtained from the stem below
      darkened cotyledons than below lighted ones.

PMID- 16656330
TI  - A Cobalt Requirement for Symbiotic Growth of Azolla filiculoides in the Absence
      of Combined Nitrogen.
AB  - Cobalt was shown to be essential for the symbiotic growth of Azolla filiculoides
      and Anabacna azollac in the absence of fixed nitrogen. Addition of 0.01 mug/liter
      cobalt resulted in large increases in yield, chlorophyll content and nitrogen
      fixation as compared to control cultures without cobalt. Cobalt was not required
      for the growth of Azolla when nitrate nitrogen was supplied. The number of
      Anabaena azollae cells in the fronds of Azolla appeared to be decreased by
      ommission of cobalt from the culture medium containing nitrate nitrogen. It is
      concluded that cobalt is essential for the symbiotic growth of Azolla in the
      absence of combined nitrogen and it is suggested that the cobalt requirement is
      associated with the growth of Anabaena azollae.

PMID- 16656331
TI  - Reduction of the Gibberellin Content of Pharbitis Seeds by CCC and After-Effects
      in the Progeny.
AB  - Plants of Pharbitis nil were treated with the growth retardant (2-chloroethyl)
      trimethylammonium chloride (CCC) shortly before and after anthesis. Fresh and dry
      weight of immature seeds were not affected by the CCC treatment.The level of
      gibberellin-like activity in Pharbitis seeds as compared to control seeds was
      strongly reduced by CCC application. The progenies of the treated plants also had
      a much reduced GA content in the seedling stage. These results are interpreted to
      indicate that CCC blocks gibberellin biosynthesis in higher plants, as it does in
      the fungus Fusarium.CCC applied via the roots accumulated in the immature seeds
      and was carried over to the following generation. Consequently, growth of CCC
      progenies was dwarfed and flower formation inhibited. Both phenomena were
      overcome by application of gibberellin A(3).Three gibberellin-like substances
      (called fractions I, II, and III) were present in Pharbitis seeds and could be
      separated by thin-layer chromatography. All 3 fractions were also present in
      seeds treated with CCC. Fractions II and III were present in much higher
      quantities than fraction I. Both fractions II and III promoted growth of d5 corn
      but only fraction II was active in dwarf peas grown under red light.

PMID- 16656332
TI  - Dual mechanisms of ion uptake in relation to vacuolation in corn roots.
AB  - Absorption isotherms for chloride and rubidium ions have been determined through
      a wide concentration range for nonvacuolate root tips, and for vacuolate
      subapical sections of corn root. In the range 0 to 0.5 mm, chloride absorption is
      hyperbolic with concentration in both tips and proximal sections. At high
      concentrations, 1 to 50 mm, a second multiple-hyperbolic isotherm for chloride is
      noted in vacuolate tissue, while the isotherm for nonvacuolate tips rises
      exponentially. A linear to exponentially rising isotherm is taken to signify
      diffusive permeation.The same distinction between tip and subapical tissue
      characterizes Rb absorption. Rb uptake is indifferent to the nature of the
      counterion at all concentrations in the tip, while the counterion exerts a
      predictable influence on Rb absorption in proximal tissue. The effect of a poorly
      absorbable anion on Rb uptake is greater in the high concentration range.
      Evidence is presented for the metabolic nature of ion transport into nonvacuolate
      root tips. Verification is offered that ion uptake is mediated by dual
      mechanisms, and the thesis is developed that the high-affinity (low K(s)) system
      mediates ion passage through the plasma membrane while the low-affinity (high
      K(s)) system implements transport through the tonoplast.

PMID- 16656333
TI  - Auxin and gibberellin effects on cell growth and starch during abscission in
      cotton.
AB  - An increase in starch content of cells in the abscission zone of the cotton
      explant appeared correlated with an increase in number of cells. A large increase
      in the number of cells in the abscission zone, concomitant with an increase in
      starch content, followed treatment with gibberellin as compared to auxin. In the
      final stages of abscission starch was hydrolyzed in the cells of the separation
      layer. Some starch remained after the petiole abscised.A positive phloroglucinol
      hydrochloric acid reaction in the cells of the petiole distal to the line of
      separation indicated the presence, not of lignin, but of soluble sugars and
      uronic acids. This reaction was especially intense following gibberellic acid
      treatment.It was concluded that gibberellin in accelerating abscission leads to
      (1) an increase in cell number and starch content in the abscission zone, (2) the
      hydrolysis of starch in the separation layer just before abscission, and (3) the
      breakdown of polysaccharides and the release of soluble sugars and uronic acids.
      Auxin, an abscission retardant, either delays or prevents these events.

PMID- 16656334
TI  - Ethylene as a factor regulating the growth of pea epicotyls subjected to physical
      stress.
AB  - Pea epicotyls (Pisum sativum, cv. Alaska) were enclosed in chambers in which
      their elongation was restricted by means of a foam neoprene stopper or by a
      medium of glass beads. These treatments increased evolution of ethylene and
      resulted in reduced length and increased diameter of both the internodes and the
      cells of the internodes. These responses increased with increasing degrees of
      restriction. A time-sequence study of the emergence of epicotyls through 90 mm of
      glass beads showed that an accelerated evolution of ethylene preceded a reduction
      in elongation. As the epicotyls elongated through the glass bead medium and less
      resistance was encountered, evolution of ethylene declined and rapid elongation
      was resumed. The morphological and anatomical effects of a 120-mm column of glass
      beads were duplicated by applied ethylene concentrations of 0.2 ppm or less.
      Evolution of CO(2) was inhibited slightly by the ethylene treatments. The data
      indicate that production of ethylene by pea epicotyls is increased by nonwounding
      physical stress, and that the ethylene acts as an endogenous growth regulator,
      decreasing elongation and increasing diameter in response to increasing
      increments of stress.

PMID- 16656335
TI  - Regulation of Photosynthetic Capacity in Chlamydomonas mundana.
AB  - A regulatory system has been described in the obligately phototrophic green alga
      Chlamydomonas mundana. Cells grown in acetate media are unable to fix carbon
      dioxide in the light but carry out a photoassimilation of acetate to
      carbohydrate: cells cultured with carbon dioxide as the sole source of cellular
      carbon carry out typical green plant photosynthesis. The control appears to take
      place at the level of the reductive pentose phosphate cycle. The presence of
      sodium acetate in the medium strongly inhibits formation of ribulose-1.5
      diphosphate carboxylase, ribulose-5-phosphate kinase, and one of the 2 fructose
      1,6-diphosphate aldolase activities of the cell. Ribose-5-phosphate isomerase is
      present in higher activity in autotrophic cells. Changes in the levels of triose
      phosphate dehydrogenase were also noted. The total pigment content of the cell
      and the photosynthetic electron transport reactions are not altered under
      different conditions of growth.

PMID- 16656336
TI  - Action spectrum and characteristics of the light activated disappearance of
      phytochrome in oat seedlings.
AB  - The action spectrum for the light-activated destruction of phytochrome in
      etiolated Avena seedlings has been determined. There are 2 broad maxima, one
      between 380 and 440 mmu, the other between 600 and 700 mmu. peaking at about 660
      mmu. On an incident energy basis, the red region of the spectrum is more
      efficient than the blue by about one order of magnitude in activating phytochrome
      disappearance. Both the red absorbing as well as the far-red absorbing forms of
      phytochrome are destroyed after exposure of Avena seedling to either red or blue
      light.From the action spectrum and photoreversibility of pigment loss, we
      conclude that phytochrome acts as a photoreceptor for the photoactivation of its
      metabolically-based destruction. We suggest that another pigment might also be
      associated with the disappearance of phytochrome in oat seedlings exposed to blue
      light.

PMID- 16656337
TI  - Role of Indole-3-acetic Acid in Modification of Geotropic Responses in Clinostat
      Rotated Avena Seedlings.
AB  - Oat seedlings were grown in a sand medium on clinostats with horizontal axes of
      rotation to nullify the directional component of the gravity-force vector.
      Coleoptile segments from such seedlings showed an enhanced absorption of apically
      applied exogenous auxin (indole-3-acetic acid), compared to segments from
      vertically rotated or stationary controls. Absorption of basally applied auxin
      and auxin transport were unaffected by the gravity treatments. Horizontal
      rotation did not materially change the amount of auxin produced and transported
      from excised coleoptile tips: however, plants so rotated showed an enhanced
      curvature response to unilaterally applied auxin.Collectively, these experiments
      indicate that enhanced plant responses to horizontal clinostat rotation, where
      rates of rotation are sufficient to nullify the directional component of the
      gravity-force vector, are caused primarily by increases in metabolism and not by
      a modification of auxin availability. These data do not support recently advanced
      hypotheses that the polarity of auxin transport is based on gravitational
      sedimentation of cell inclusions.

PMID- 16656338
TI  - Direct Assay of IAA Decarboxylation Rate in Excised Tobacco Pith: Relation to
      Aging.

PMID- 16656339
TI  - Transmission error in the photometric estimation of leaf area.

PMID- 16656340
TI  - Responses of Avena and pisum tissues to phytochrome conversion by red light.

PMID- 16656341
TI  - A raffinose-sucrose transgalactosidase from wheat germ.

PMID- 16656343
TI  - Calcium-activated phosphate uptake in contracting corn mitochondria.
AB  - The phosphate inhibition of succinate-powered contraction in corn mitochondria
      can be reversed with calcium. Associated with this reversal is an accumulation of
      phosphate and calcium. Both ions are essential for accumulation, although
      strontium will partially substitute for calcium. Arsenate does not substitute for
      phosphate except in producing the inhibition of contraction.The antibiotics
      oligomycin and aurovertin do not block the phosphate inhibition of contraction or
      the calcium-activated phosphate uptake associated with the release of the
      inhibition. Dinitrophenol uncouples the phosphate uptake but permits full
      contraction.Calcium promotes inorganic phosphate accumulation in root tissue as
      well as in mitochondria.The results are discussed from the viewpoint of theories
      of calcium reaction with high energy intermediates of oxidative phosphorylation.
      It is concluded that calcium probably reacts with X approximately P in corn
      mitochondria, rather than with X approximately I as with animal mitochondria.

PMID- 16656344
TI  - Physiological studies on pea tendrils. I. Growth and coiling following mechanical
      stimulation.
AB  - Unbranched tendrils arising from the fifth node of light grown Alaska pea plants
      were found to reach maturity at the age of 10 days. Such tendrils, when stroked,
      coiled rapidly. They remained maximally irritable for at least 3 days.Coiling was
      separable into 2 components, curvature (measured in degrees) and elongation.
      Coiling reached a maximum from one-half to 3 hours after tactile stimulation.
      This maximum is followed by a decrease, then by a further increase up to 48
      hours.The optimum temperature range for curvature was 16 to 30 degrees after 2
      hours and 16 to 20 degrees after 20 hours. Curvature was minimal and elongation
      optimal at a pH of 6.6. Both curvature and elongation were greater in white light
      than in darkness.Severing the dorsal vascular bundles decreased coiling, whereas
      severing the ventral bundles had no effect. Amputation of the tip of an excised
      tendril increased curvature but decreased elongation. In some cases, coiling of
      tendrils in situ was followed by curvature of the subjacent stem.Various growth
      substances produce effects on elongation and curvature of tendrils in vitro, in
      light and dark. CCC and GA decrease curvature in the light and increase curvature
      in the dark and elongation in the light and in the dark. Kinetin decreases
      curvature in the light, increases it slightly in the dark and has no effect on
      elongation. IAA increases elongation in the light and in the dark at
      concentrations above 10(-6)m. At lower concentrations, curvature was increased in
      the light and decreased in the dark.These data are discussed with a view towards
      explaining the coiling event.

PMID- 16656345
TI  - Photoinhibition of chloroplast reactions. I. Kinetics and action spectra.
AB  - A study was made of photoinhibition of spinach chloroplast reactions. The
      kinetics and spectral characteristics of the photoinhibition over a range between
      230 and 700 mmu have been examined. The decline of activity due to
      preillumination was independent of wavelength, and dependent upon the number of
      quanta applied, not upon the rate of application. The effectiveness spectra of
      photoinhibition indicate that active ultraviolet light is absorbed by a pigment
      which is not a normal light absorber for photosynthesis and acts with a high
      quantum efficiency (> 0.1) for photoinhibition.Active visible light is absorbed
      by the pigments which sensitize photosynthesis (chlorophyll, carotenoids). A very
      low quantum efficiency (about 10(-4)) was observed for the photoinhibition with
      visible light.The action spectrum of the photoinhibition of dye reduction by
      chloroplasts and lyophylized Anacystis cells indicated that the damage caused by
      visible light is due to quanta absorbed by photosystem II. However, since system
      I might not be involved in dye reduction, the spectra may reflect only damage to
      photosystem II.

PMID- 16656346
TI  - Photoinhibition of Chloroplast Reactions. II. Multiple Effects.
AB  - Ultraviolet light inhibits the photoreduction of 2,6-dichlorophenolindo-phenol or
      nicotinamide adenine dinucleotide phosphate with water as the electron donor
      (evolution of oxygen) but not the photoreduction of nicotinamide adenine
      dinucleotide phosphate with ascorbate as the electron donor. It inhibits
      photophosphorylation associated with either system. Experiments undertaken to
      test whether plastoquinone is the site of UV inhibition yielded inconclusive
      results.Visible light (> 420 mmu) causes the loss of all chloroplast activities,
      photosystem I being more sensitive than system II. The data suggests 2 modes of
      action for visible light. The one sensitized by system II results in damage
      resembling that of UV light. The other, sensitized by system I, results in the
      destruction of the reaction center of this system.

PMID- 16656347
TI  - Survival of Plant Tissue at Super-Low Temperatures. IV. Cell Survival with Rapid
      Cooling and Rewarming.
AB  - Thin unmounted cortical tissue sections from winter twigs of the mulberry tree
      were held with a thin forceps and rapidly immersed in liquid nitrogen from room
      temperatures without prefreezing. They were rewarmed; rapidly in water at 10
      degrees to 40 degrees , or slowly, in air at room temperatures. In those sections
      rapidly rewarmed, all survived. None survived in those sections rewarmed slowly
      in air.Tissue sections mounted between coverglasses with water were
      extracellulary prefrozen at the temperatures low enough to dehydrate almost all
      of the freezable water in cells. These sufficiently prefrozen cells could survive
      immersion in liquid nitrogen, and the survival value was very little affected by
      the rates of cooling to and rewarming from super-low temperatures. With
      insufficient prefreezing at higher temperatures, however, the rewarming process
      seriously influenced the survival value of cells frozen at super-low
      temperatures. Slow rewarming in air destroyed all of the cells, while rapid
      rewarming in water at 30 degrees did not affect them. An abrupt decrease in the
      survival value in insufficiently prefrozen cells during rewarming was also
      observed at temperatures above approximately -50 degrees following immersion in
      liquid nitrogen. Very little decrease in the survival value was observed in any
      of the cells that had been sufficiently prefrozen.These results indicate that
      cells which are insufficiently prefrozen may contain freezable water which
      nucleates during rapid cooling in liquid nitrogen and then grows during the
      subsequent slow rewarming into ice masses which destroy the viability of the
      cells. Such fatal intracellular freezing rarely occurs in sufficiently prefrozen
      cells, irrespective of the rate of cooling to or rewarming from super-low
      temperatures.

PMID- 16656348
TI  - Control by phytochrome of C-sucrose incorporation into buds of etiolated pea
      seedlings.
AB  - When etiolated pea epicotyls are excised immediately above the cotyledons and
      dipped basally into (14)C-sucrose, their terminal buds respond to red light by
      increased growth (IG) and enhanced incorporation of sucrose (EIS). Both phenomena
      are phytochrome controlled, showing typical kinetics, reversal by far-red light,
      escape from photochemical control and limitation to leaf tissue. EIS is of
      greater magnitude, occurs more rapidly and is saturated by lower energies of red
      light than IG, suggesting its possible importance as a controlling reaction in
      phytochrome-mediated growth. Both IG and EIS are best shown in the presence of a
      long epicotyl derived from a 5 to 6-day-old seedling in the presence of about 0.1
      m unlabeled sucrose in the medium.Enhanced incorporation is most dramatic with
      sucrose; lesser effects are shown with fructose, glucose, maltose and ribose in
      that order. Both level of incorporation and red light effects are poor for
      labeled tyrosine, phenylalanine, valine, acetic acid, cinnamic acid and alpha
      ketoglutaric acid. The possible connection between carbohydrates and phytochrome
      mediated photomorphogenesis is considered.

PMID- 16656349
TI  - Orientation of wheat seedling organs in relation to gravity.
AB  - Seedlings of wheat (Triticum aestivum L.) were grown in special holders that
      permitted the coleoptile and early roots to develop in moist air. The orientation
      of the organs of seedlings erect to gravity was compared with that of organs
      produced on a horizontal clinostat. Orientation was described by the angular
      position of each organ tip with reference to the axis of the embryo. Comparative
      tests were also made with barley, rye, and oat seedlings.The coleoptile of all
      species developed curvatures in 3 dimensions when geotropic responses were
      eliminated. The primary root was not precise in its positive geotropism.
      Seedlings grew on clinostats with much greater variations in the lateral
      orientation of the central root and with a tendency for it to curve away from the
      endosperm to a greater degree than in erect seedlings.The symmetry of root system
      in wheat was found to depend on a specific mechanism. Under the influence of
      gravity the earliest lateral roots were oriented in a plane at characteristic
      angles of about 57.5 degrees with the ideal primary root. The corresponding
      angles for lateral roots growing on clinostats were greater by about 47.5 degrees
      as a result of epinasty not previously reported in roots. This force also
      appeared to be active in the seminal roots of barley and rye but not of oats.The
      curvatures in coleoptiles grown without the directional effects of gravity
      correspond to the results of growth imbalance in Coleus stems in the absence of
      lateral transport of their auxin by gravity. Root epinasty appears to be based on
      auxin imbalance. Curvatures in the primary root are also interpreted as results
      of asymmetrical distribution of growth hormone.

PMID- 16656350
TI  - Effect of Gibberellic Acid on the Senescence of Leaf Discs of Nasturtium
      (Tropaeolum majus).

PMID- 16656351
TI  - New methods for effecting watertight seals on corn roots.

PMID- 16656352
TI  - Florigenic Acid from fungal culture.
AB  - The extraction procedures which have been successfully employed in the
      preparation of a florigenic principle from the tissues of Xanthium, are
      applicable to the derivation of an entity of similar activity from Calonectria
      culture. The Xanthium principle is acedic, with pK(a) values characteristic of a
      carboxylic acid (6). Although definitive chemical comparisons have not been
      completed, the extraction and solvent partition procedures that have been
      applicable to the extraction of the active entity from higher plant tissues have
      yielded florigenic preparations from fungal culture. The chemical principle from
      higher plant tissue may be the same or similar to the florigenic agent of
      Calonectria.The many responses of higher plants to growth regulators produced by
      micro-organisms are well known. The presence of a flower-producing principle from
      Calonectria (Fusarium) rigidiuscula parallels closely the pattern exhibited by
      those fungal species capable of the production of auxin and gibberellins.

PMID- 16656353
TI  - Pigment composition and optical rotatory dispersion of chloroplast fractions
      obtained by detergent action.

PMID- 16656354
TI  - Intracellular location and possible function of malic dehydrogenase isozymes from
      young maize root tissue.

PMID- 16656355
TI  - Effects of Light Intensity on Photosynthetic Carboxylative Phase Enzymes and
      Chlorophyll Synthesis in Greening Leaves of Hordeum vulgare L.
AB  - The effects of various light intensities on in vivo increases in activities of
      phosphoriboisomerase, phosphoribulokinase and ribulose-1, 5-diP carboxylase and
      on synthesis of chlorophyll were studied in greening leaves of Hordeum vulgare
      L.Each enzyme was already present in dark-grown plants, but further increases in
      activities required both a light treatment of the intact plant and a favorable
      temperature. The amount of enzymatic activity and chlorophyll developed was
      governed by light intensity.Measured activities of phosphoriboisomerase and
      ribulose 1,5-diP carboxylase were highly correlated with synthesis of chlorophyll
      at all intensities studied. Measured activity of phosphoribulokinase was
      correlated with synthesis of chlorophyll only at saturating or near saturating
      light intensities. At decreasing light intensities the response curves of this
      enzyme differed from those of chlorophyll and of phosphoriboisomerase and
      ribulose-1, 5-diP carboxylase. A lag period of phosphoribulokinase increased with
      decreasing light intensity. After the lag period a rapid rate of increase
      occurred which did not level off during 48 hours of illumination. Thus, a
      different control mechanism may be operative in inducing increased activity of
      this enzyme.

PMID- 16656356
TI  - Effects of protein inhibitors and auxin on nucleic Acid metabolism in peanut
      cotyledons.
AB  - The accumulation of labeled phosphorus into newly synthesized nucleic acids or
      peanut cotyledon slices incubated with chloramphenicol, puromycin, or 2,4
      dichlorophenoxyacetic acid (2,4-D) was reduced. Promotion of nucleic acid
      synthesis was not noted by any of these chemicals. Chloramphenicol completely
      inhibited the synthesis of the DNA-RNA fraction at 1.25 x 10(-3)m while soluble
      and ribosomal RNA was inhibited by 70% and 80%, respectively. At the same
      concentration messenger RNA was inhibited by only 40%. These effects suggest that
      chloramphenicol inhibit nucleic acid synthesis in peanut cotyledons in a
      differential manner. Similar results were noted for DNA at low concentrations of
      2,4-D. However, at high concentrations of 2,4-D, DNA as well as RNA fractions
      were inhibited in a similar manner at a given concentration. Puromycin did not
      differentially inhibit nucleic acid synthesis except at 2 x 10(-3)m where DNA was
      least inhibited.Nondifferential inhibition suggests that a common site or
      precursor pool essential for the synthesis of all nucleic acid fractions is
      altered. Differential inhibition may be due to the interference with a specific
      rate-limiting step, directly or indirectly, in the formation of a particular
      nucleic acid.

PMID- 16656357
TI  - Sugars and Organic Acids of Vitis vinifera.
AB  - Glucose, fructose, galactose, sucrose, maltose, melibiose, raffinose, and
      stachyose were identified in the leaves, bark, roots, and berries of Vitis
      vinifera L. var. Thompson Seedless. In addition to these sugars, verbascose and
      manninotriose were found in the leaves and bark.Malic, tartaric, citric,
      isocitric, ascorbic, cis-aconitic, oxalic, glycolic, glyoxylic, succinic, lactic,
      glutaric, fumaric, pyrrolidone carboxylic, alpha-ketoglutaric, pyruvic,
      oxaloacetic, galacturonic, glucuronic, shikimic, quinic, chlorogenic, and caffeic
      acids were identified in the leaves, bark, roots, and berries.Glucose, fructose,
      sucrose, malate, tartrate, and citrate were determined quantitatively in the
      leaf, petiole, xylem, bark, tendril, bud, puduncle pedicel, berry, lateral roots,
      and main roots at 4 separate physiological stages of growth. In addition, changes
      in the concentrations of fructose, glucose, malate, and tartrate in leaves were
      measured during a 36-day period starting from budburst.

PMID- 16656358
TI  - Phytochrome changes correlated to mesocotyl inhibition in etiolated Avena
      seedlings.
AB  - The elongation of etiolated Avena mesocotyls is inhibited by red light (660 mmu).
      Immediately after exposing mesocotyl sections to varying doses of red light the
      ensuing concentrations of phytochrome in the far-red absorbing form (P(730)) were
      measured. The extent of mesocotyl inhibition observed 5 days later is
      proportional to the logarithm of P(730) concentration in mesocotyl tissue at the
      time of red light exposure.The inhibition of mesocotyl growth by red light can be
      reversed partially by subsequent exposure to far-red light (730 mmu). Increasing
      doses of far-red light result in decreasing concentrations of P(730) as compared
      with the original P(730) level due to the preceding red light exposure. The
      reduced mesocotyl inhibition of seedings which had been exposed to red and far
      red light is proportional to the logarithm of P(730) concentration remaining in
      the tissue at the end of the two light exposures.This indicates that the same
      correlation exists between P(730) concentration and growth response whether the
      seedlings had been exposed to red light only or to red followed by far-red light.

PMID- 16656359
TI  - Photoreduction of Pyridine Nucleotide by Subcellular Preparations from
      Rhodopseudomonas spheroides.
AB  - We have investigated the photoreduction of pyridine nucleotides by crude extracts
      and chromatophores of Rhodopseudomonas spheroides.Our findings are as
      follows:NADP is preferentially photoreduced by crude extracts (37,000 x g
      supernatant fraction) and there is no requirement for the addition of exogenous
      substrates. Crude extracts also catalyze a nonphotosensitive reduction of
      NAD.NADP photoreduction is completely inhibited if an NADH trapping system is
      present and indicates that NADH is required for NADP photoreduction.Washed
      chromatophores (150,000 x g pellet) do not catalyze NADP photoreduction unless
      the supernatant fraction is added. The restoring effect of supernatant fraction
      is lost upon boiling and dialysis. However, supernatant materials can be replaced
      by an NADH generating system. There is no requirement for anaerobic
      conditions.Evidence has been presented which suggests that Rhodopseudomonas
      spheroides contains an energy-linked transhydrogenase that can be driven by a
      high energy intermediate generated by light or ATP. This intermediate may also be
      functional in ATP synthesis. The synthesis of ATP and the ATP-supported
      transhydrogenase is inhibited by oligomycin. This inhibitor does not affect the
      light-mediated reaction.

PMID- 16656360
TI  - Substitution of redox chemicals for radiation in phytochrome-mediated
      photomorphogenesis.
AB  - The reducing agents, potassium ferrocyanide, beta-mercaptoethylamine, cysteine,
      reduced DPN, ferrous sulfate, methyl viologen and ascorbic acid caused the
      expansion in darkness of disks of primary leaf tissue cut from dark-grown bean
      plants. The reducing agents interacted synergistically with low irradiances of
      red radiation and additively with high irradiance of red light. Exposure of disks
      treated with reducing agents to far red light repressed disk expansion and the
      decay in sensitivity to far red radiation showed the same time relations as
      sequential exposure to red and far red radiation.The oxidizing agents, 1,4
      naphthoquinone, ferric sulfate, hydrogen peroxide, t-butyl hydroperoxide,
      cystine, and potassium ferricyanide repressed the expansion of leaf disks
      initiated by exposure to red radiation. The oxidizing agents interacted
      synergistically with low irradiances of far red light and additively with
      irradiances of far red light.

PMID- 16656361
TI  - Regulatory Mechanisms in Anthocyanin Biosynthesis in First Internodes of Sorghum
      vulgare: Effect of Presumed Inhibitors of Protein Synthesis.
AB  - There was a 6 to 24-hour lag in the production of anthocyanins in the light after
      excision of 4-day-old etiolated internodes of Sorghum vulgare variety Wheatland
      milo. In internodes infiltrated with water, apigeninidin was formed first at 12
      to 24 hours and continued to be produced slowly. Luteolinidin was formed slightly
      later, but its formation rapidly exceeded that of apigeninidin. Cyanidin was the
      last type to be produced, but equaled the amounts of luteolinidin by 4 days. In
      noninfiltrated internodes, the production of cyanidin was greatly accelerated,
      beginning at about 6 hours.Data from experiments with inhibitors that presumably
      affect protein synthesis at different loci indicated that protein synthesis was
      necessary for maximum production of all 3 anthocyanins, but that different steps
      were rate limiting. Light independent synthesis of apigeninidin and luteolinidin
      was inhibited by chloramphenicol and l-ethionine but not by actinomycin D and 8
      azaguanine. However, the synthesis of these 2 anthocyanins was not inhibited by
      puromycin, but was sometimes stimulated. The light-induced synthesis of cyanidin
      was inhibited by actinomycin, azaguanine, chloramphenicol and ethionine.
      Actinomycin no longer was inhibitory if added after incubation for 6 hours in
      air. All inhibitors were capable of inhibiting to various degrees either the
      incorporation of (14)C-uracil into RNA or (14)C-leucine into protein. The
      inhibitor data suggest that the light insensitive synthesis of apigeninidin and
      luteolinidin may be controlled by enzyme synthesis at the level of ribosomes via
      stable mRNA, while the light-induced production of cyanidin is dependent
      initially on the production of mRNA. The latter hypothesis is similar to that
      recently proposed by Lange and Mohr for a cyanidin produced in Sinapis seedlings.

PMID- 16656362
TI  - Mediation of phytochrome in the inductive action of low temperature on dark
      germination of lettuce seed at supra-optimal temperature.
AB  - The induction of dark germination in light-requiring lettuce (Lactuca sativa)
      seed at supraoptimal temperatures by cold treatment (in darkness) was partly
      reversed by a brief far-red irradiation made at time of transfer, and even more
      so when the irradiation was made at the beginning of the cold pretreatment. When
      the inhibitory far-red irradiation was followed by additional cold treatment, the
      promotion was greatly restored. The promotive effects of brief irradiations with
      red light were further enhanced by a following cold period, before transfer to
      the supraoptimal temperature. These results are interpreted as indicating that
      the active (far-red absorbing) form of phytochrome is pre-existing in the dry
      seed, and interacts with a co-factor which is built-up during imbibition. The
      rate of build-up of this co-factor, as well as of the dark inactivation of active
      phytochrome increase with temperature. The products of the interaction pass
      through a photo-labile thermo-stable phase, before becoming photo-stable as well.

PMID- 16656363
TI  - DNA synthesis in the elongating nondividing cells of the lentil epicotyl and its
      promotion by gibberellin.
AB  - Two-day-old lentil seedlings, (Lens culinaris Med.) were incubated for a 48-hour
      period with and without gibberellin (GA) in the presence and absence of 5
      fluorodeoxyuridine (FUDR). The number of cells per epicotyl did not increase
      during this period. Growth of the epicotyl was thus due to cell elongation
      alone.The elongating cells of this tissue synthesized DNA. GA promoted and FUDR
      inhibited cell elongation, DNA synthesis, and RNA synthesis in the tissue.FUDR
      promoted uptake of thymidine and thymidine incorporation into cellular DNA,
      presumably by inhibiting synthesis of endogenous thymidine. Presence of GA
      promoted thymidine incorporation into cellular DNA and uridine incorporation into
      cellular RNA. In either case, there was no effect on the uptake of the precursor
      into the tissue.Fractionation of thymidine-labeled nucleic acids on a MAK column
      showed that thymidine was exclusively incorporated into the DNA fraction.
      Presence of GA promoted thymidine incorporation into this fraction and also
      increased the amount of ribosomal RNA.The data provide direct evidence for the
      conclusion that DNA synthesis is necessary for elongation of certain plant cells.

PMID- 16656364
TI  - Growth inhibition of tobacco tissue cultures with 6-azauracil, 6-azauridine and
      maleic hydrazide.
AB  - Tissue cultures of Nicotiana tabacum, Nicotiana suaveolens and Nicotiana
      suaveolens x Nicotiana langsdorffii were cultured in the presence of the growth
      inhibitors maleic hydrazide and 6-azauracil as well as 6-azauridine. Inhibition
      of growth was complete at 10(-4) molar concentrations in all 3 genotypes of
      cells. The inhibition due to 6-azauracil could be completely relieved with
      uridine and partially relieved with uracil. The effect with maleic hydrazide was
      irreversible, a fact which indicates a different mechanism or level of
      inhibition. This study supports the concept that derivatives of 6-azauracil
      inhibit the synthesis of uridine derivatives required for ribose nucleic acid
      synthesis and growth.

PMID- 16656365
TI  - Association of D-RNA with Polyribosomes in the Soybean Root.
AB  - Ribosomes from soybean root tips were shown to consist of about 75% polyribosomes
      based on size distribution on sucrose gradients. Electronmicrographs showed the
      presence of ribosome clusters in normal preparations and only monomers and dimers
      in ribonuclease-treated preparations. The polyribosome preparations, but not
      single ribosomes, showed good in vitro amino acid incorporating activity.D-RNA
      was associated with the ribosome preparations, and preferentially in the
      polyribosome structure. It is suggested that at least a part of the soybean D-RNA
      represents a class of messenger RNA.

PMID- 16656366
TI  - Laser activation of rapid absorption changes in spinach chloroplasts and
      chlorella.
AB  - The kinetics of the 520 mmu absorption change in spinach chloroplasts and
      Chlorella vulgaris following a flash from the ruby laser have been determined as
      follows: rise halftime </= 0.3 x 10(-6) second; rapid recovery halftime = 5 to 6
      x 10(-6) second; intermediate recovery halftime = 4 x 10(-4) second (spinach
      chloroplasts only); slow recovery halftime = 12 to 170 x 10(-3) second, dependent
      on the measuring light intensity and aerobicity of the suspension.The rapid phase
      of the 520 mmu reaction is approximately independent of temperature, from 295
      degrees to 77 degrees Absolute.With increasing oxygenation of the sample, the
      extent of the rapid phase decreases, the extent of the slow phase increases,
      while the extent of the intermediate phase in spinach chloroplasts remains
      constant.In spinach chloroplasts, no recovery halftime of the 3 recovery phases
      for the 520 mmu absorption change was observed to correspond to the halftime for
      oxidation of cytochrome f (t((1/2)) = 1.3 x 10(-3) second).

PMID- 16656367
TI  - Effect of Chloramphenicol on Formation of Chloroplast Structure and Protein
      During Greening of Etiolated Leaves of Phaseolus vulgaris.
AB  - Greening of leaves of Phaseolus vulgaris in the presence of chloramphenicol
      inhibits formation of A) total chloroplast protein, B) an easily extractable
      fraction removed during isolation of chloroplasts in isotonic media by
      differential centrifugation, and C) the insoluble lamellar fraction which remains
      after extracting osmotically shocked freeze-dried plastids. The inhibition of
      insoluble chloroplast protein formation is correlated with decreased formation of
      lamellae and increased formation of vesicular structures. In contrast,
      chloramphenicol increases the formation of a fraction not removed during
      differential centrifugation, but removed by water extraction after osmotic shock
      and freeze-drying of chloroplasts. Analysis of this fraction by electrophoresis
      and column chromatography, indicates that the increased accumulation of this
      protein fraction is largely due to accumulation of a protein which is normally
      present in this fraction in small quantities. It was suggested that this protein
      may be a precursor which is normally incorporated into the lamellae. The protein
      extracted from freeze-dried chloroplasts of chloramphenicol treated chloroplasts
      contains a smaller proportion of one or more proteins than a similar extract of
      untreated plastids. However, per plastid, no such difference exists.

PMID- 16656368
TI  - Senescence inhibition and respiration induced by growth retardants and N
      benzyladenine.
AB  - Senescence of Grand Rapids leaf lettuce was greatly reduced at 3 storage
      temperatures by post-harvest treatment with N,N-dimethylaminosuccinamic acid
      (Alar) and 2-chloroethyltrimethylammonium chloride (CCC), but not with (6)N
      benzyladenine (BA). Conversely, Alar and CCC were inactive on broccoli while BA
      was markedly effective. The deterioration and discoloration of mushrooms was
      inhibited by Alar with no effect observed from BA or CCC.The inhibition of
      senescence by BA and the growth retardants was not always associated with a
      reduction in respiration (O(2) uptake, CO(2) evolution). BA stimulated
      respiration and hastened senescence in leaf lettuce accompanied by a
      diametrically opposite effect from Alar and CCC. Thus, BA cannot be considered a
      universal senescence inhibitor. The variability of senescence responses induced
      by different chemicals on a variety of plant tissues suggests a dissimilar mode
      of action or a complex interaction with native growth substances.

PMID- 16656369
TI  - Gibberellins of sugarcane.
AB  - In our hands a phosphate buffered celite column has given an adequate separation
      of GA(1) and GA(3). These 2 gibberellins are normally very difficult to separate.
      Young sugarcane growing under moisture stress contains at least 2 gibberellin
      like substances. One is suspected to be GA(5). The other is unknown but has high
      activity in the barley endosperm assay and is neither GA(1) nor GA(3). Four-month
      old cane contains 2 major growth promoters. From their chromatographic,
      fluorimetric and biological properties these are thought to be GA(1) and GA(3).
      Rapidly growing 6-month-old cane has a surprisingly low level of gibberellin-like
      substances.

PMID- 16656370
TI  - Iron uptake and translocation by tomato plants as influenced by root temperature
      and manganese nutrition.
AB  - The uptake of iron (Fe) by VF-36 tomato plants as influenced by root temperature
      and manganese (Mn) nutrition was studied. Following a 1-week pretreatment period
      of various levels of Fe and Mn in the nutrient solution in a controlled
      temperature room, the uptake of (59)Fe from ferric ethylenediamine di(O
      hydroxyphenylacetate) (FeEDDHA) at 1 mumole per liter was studied for periods of
      1 to 5 days.Both Fe uptake and translocation were enhanced by increases in root
      temperature. Varied levels of Fe in the pretreatment period led to increased
      levels of Fe in the plant, which subsequently depressed further accumulation of
      (59)Fe. The effect of increased root temperature on (59)Fe uptake and
      translocation was decreased by increases in the level of Fe in the pretreatment
      cultures. As Mn in the nutrient solution was increased, (59)Fe uptake and
      translocation were increased to a point and then decreased.The degree of Fe
      saturation of the plant appeared to be a primary factor in regulating Fe uptake
      and translocation in the plant. As the Fe saturation of the plant decreased, the
      uptake of Fe in response to metabolic processes of the plant increased, as
      evidenced by increased response of absorption to root temperature.

PMID- 16656371
TI  - Vascular Regeneration and Long Distance Transport of Indole-3-acetic Acid in
      Coleus Stems.
AB  - Excision of all leaves and buds of Coleus blumei Benth. plants reduced xylem cell
      and sieve tube regeneration a highly significant amount around a wound in
      internode number 5 when compared with regeneration in intact (wounded) plants.
      Application of indoleacetic acid (IAA-(14)C) to the cut surface of internode
      number 2 restores regenerative activity around the wound in internode number 5.
      Radioactivity applied as IAA-(14)C reaches the wound area when applied at the cut
      surface of inter-node number 2 showing a logarithmic decrease with distance from
      the point of application. Chromatography showed that radioactivity was located
      close to the R(F) of IAA as well as near the solvent front.Addition of
      gibberellic acid to IAA-(14)C did not change the pattern of radioactivity
      throughout the stem.

PMID- 16656372
TI  - Auxin Transport in Zea mays L. Coleoptiles I. Influence of Gravity on the
      Transport of Indoleacetic Acid-2-C.
AB  - (14)C-methylene labeled IAA was used to determine the influence of reorientation
      with respect to gravity on auxin transport in Zea mays L. coleoptile segments. It
      was observed that inversion of the segments leads to a decrease in the capacity
      to transport (14)C-IAA basipetally, as well as, in certain instances, the linear
      velocity of that transport. Segments were also reoriented horizontally, and the
      transport velocity and capacity of the upper and lower tissue halves compared
      with vertical halves. There was no significant change in the velocity, but the
      transport capacity of lower halves was higher than that of the vertical halves,
      which in turn was higher than the capacity of the horizontal upper halves. It is
      suggested that the geocurvature of horizontally placed coleoptiles may be caused
      primarily by the effect of reorientation on auxin transport.

PMID- 16656373
TI  - Photosynthate transport using tritiated water.
AB  - The exchange of HTO with aerial portions of the soybean was studied under a
      variety of conditions. When fed to a lone leaf or leaflet in a saturated air
      atmosphere (all other leaves and the growing point having been excised), the HTO
      profile virtually ceases at a distance of 2 cm from the feeding chamber in the
      photosynthetic plant, but is greater and more extensive in the unilluminated
      plant. The differences are accentuated when roots are excised. Under these latter
      conditions the photosynthetic T-fixed gradient virtually disappears.HTO was
      exchanged with darkened petioles. When the rest of the shoot was kept in the
      light (the leaf being in a saturated H(2)O-vapor atmosphere) atmosphere) almost
      half the activity moves acropetally, and under these conditions (35 min, room
      temp) over 8% may be found in the leaf. Approximately one-tenth moves
      basipetally, with none being found in the stem. When the leaf is dark, no
      movement occurs out of the petiolar feeding chamber.An attempt was made to
      distinguish between sucrose transport by diffusion and mass flow of water by
      means of 2 mathematical models. In Model I, self-diffusion of HTO, Fick's Law was
      used, with the water and photosynthate moving independently. Model I consisted of
      an equilibrated, single pool of constant specific activity, generating a
      radioactive profile as a result of self-diffusion. In Model II, mass flow, water
      exchanged freely between the phloem and the surrounding tissues. The conducting
      bundle, 7790 micron(2), (0.25% of the total cross-section) was an average phloem.
      The numerical solution for the second model was obtained by Fortran programming
      on a digital computer and compared with experimental data. Comparison of these
      models with the experimental results suggest that mass flow is not a dominant
      process in soybean photosynthate translocation.

PMID- 16656374
TI  - Apetiolar photosynthate translocation.
AB  - Apetiolar transport of photosynthate (-14)C has been studied by feeding of
      (14)CO(2) to soybean petioles. Translocation occurs in the absence of leaves, but
      both the rate and velocity are diminished. The effect of root excision is not as
      profound as that of leaves. It appears, in some instances, to inhibit transport
      partially, so that accumulation of photosynthate develops, giving a steeper
      isotopic gradient. The effect of leaf darkening is to diminish its uptake of
      photosynthate from the petiole, possibly as a result of decreased transpiration
      in the lowered temperature of the darkened leaf. The data suggest that neither
      mass flow nor active transport provide an adequate basis for normal photosynthate
      transport but that the leaves provide a direct force requiring structural
      continuity, or a translocation carrier.

PMID- 16656375
TI  - Metabolism of corn roots in malonate.
AB  - The rate of O(2) uptake by sub-apical corn roots is largely resistant to 0.1 m Na
      malonate at pH 5.0. The resistance of this tissue, in which the tricarboxylic
      acid cycle is very active, is not due to the compensatory induction of another
      oxidative pathway as seems to be the case in fresh potato slices. In corn roots
      malonate inhibits succinate utilization as expected and the smallness of the
      effect on O(2) uptake is due to the utilization of endogenous (cytoplasmic)
      malate as acetyl acceptor and its conversion to succinate. Malonate uptake stops
      after 2 to 3 hours when only a fraction (roughly 20%) of the root volume has
      equilibrated with external malonate. After this time the accumulated succinate is
      apparently able to overcome the malonate block, the ability to oxidize acetate to
      CO(2) is largely regained and O(2) uptake is maintained at about 80% of the
      control level.Malonate sensitivity at high external concentrations of malonate
      and conditions appropriate for its uptake is therefore fully expressed only under
      conditions where the production or availability of extra-mitochondrial malate (or
      perhaps other precursors of oxaloacetate) is at a minimum.

PMID- 16656376
TI  - Activation of a plant invertase by inorganic phosphate.
AB  - Activation by orthophosphate of a plant invertase from root nodules of Lupinus
      luteus L. has been demonstrated. The activation affects an increase in maximum
      velocity (V(max)) of the reaction. Activation was also achieved with a number of
      similar anions and it has been possible to infer a broad classification of anions
      capable of serving as activators. The possibility of orthophosphate activation in
      vivo has been considered, and there is some evidence to suggest that this could
      regulate invertase activity under physiological conditions.

PMID- 16656377
TI  - Wounding Response in Relation to Polar Transport of Radiocalcium in Isolated Root
      Segments of Zea mays.
AB  - A perfusion bridge technique is described which permits the continuous collection
      of exudations from both ends of corn root segments. By exposing the central
      portion of the segments to radiocalcium, the amounts and rates of tracer movement
      in either direction may be determined. Typically, a peak in both acropetal and
      basipetal transport occurs at about 90 minutes after exposure to tracer. This
      transport peak is followed by a sharp decline to relatively low transport rates.
      Thereafter the 2 perfusates from opposite ends of a segment pair show significant
      differences. The acropetal increments decrease somewhat erratically to 0 at 10 to
      12 hours, while the basipetal increments steadily increase to a steady-state
      value which remains constant from 8 to 24 hours. After a segment pair has reached
      steady-state polar transport, a fresh cut on the apical ends causes the
      resumption of acropetal transport. Such response suggests that polar transport in
      these root segments is at least partially a wound response. A possible
      explanation of the complex transport behavior is advanced.

PMID- 16656378
TI  - Physiological Studies on Pea Tendrils. II. The Role of Light and ATP in Contact
      Coiling.
AB  - Excised pea (Pisum sativum L.) tendrils incubated in the light coil more than
      those incubated in the dark. This light effect, which displays spectral responses
      characteristic of chlorophyll-mediated mechanisms, is increased by at least 8
      hours of prior dark incubation of plants from which the tendrils were derived.
      Considerable evidence indicates a major role of ATP in coiling. For example,
      inhibitors of ATP production decrease contact coiling. Exogenous ATP increases
      curvature in the dark, whereas exogenous adenosine, AMP and ADP are practically
      without effect. The ATP effect can be reversed by the addition of sucrose to the
      bathing solution. Tendrils of plants placed in the dark overnight have lower ATP
      levels than those held in the light. One half hour after stimulation, the
      endogenous ATP level of tendrils on plants kept in the light decreased fourfold.
      In the same period, the endogenous inorganic phosphate level increased markedly,
      indicating high adenosine triphosphatase activity.Curvature is proportional to
      the logarithm of the molarity of applied ATP between 10(-4) and 10(-2)m, whereas
      elongation responds only to the higher dosages. It is inferred that endogenous
      ATP is involved as an energy source in coiling, especially in the initial phase,
      which involves contraction of the tendril. The existence of a higher plant analog
      of actomyosin, suggested by others, is supported.

PMID- 16656379
TI  - The physiological versus the spectrophotometric status of phytochrome in corn
      coleoptiles.
AB  - The influence of red light in altering the phototropic sensitivity of corn
      coleoptiles (Zea mays L., cultivar Burpee Barbecue Hybrid) is compared with the
      spectrophotometric status of the phytochrome they contain. The distribution of
      measurable phytochrome corresponds roughly with the distribution of sensitivity
      to red light for physiological change. Both phytochrome concentration and red
      light sensitivity are maximal in the coleoptile tips. Red light pretreatments
      which reduce total phytochrome by about 50%, however, do not alter subsequent red
      light sensitivity of the phototropic system. Dosages of red light sufficient to
      saturate the physiological system are two orders of magnitude too small to induce
      measurable phytochrome transformation. The log-dosage-response curves for
      physiological change and for phytochrome transformation do not have the same
      slopes. The time course for appearance, mainconcentration of the far-red
      absorbing form of phytochrome over a broad range of tenance, and decay of the
      physiological response is independent of the measurable concentrations. The
      following hypothesis is proposed: the phytochrome mediating the alteration in
      phototropic sensitivity is only a small proportion of the total present. This
      small active fraction is physically and kinetically independent of the bulk
      measurable, and is packaged in some manner which facilitates its transformation
      in both directions.

PMID- 16656380
TI  - Protein Synthesis in Imbibed Seeds III. Kinetics of Amino Acid Incorporation
      Ribosome Activation, and Polysome Formation.
AB  - The kinetics of development of protein-synthesizing capacity in the imbibing
      wheat embryo, were studied both in vivo and in vitro. During the first 30 minutes
      of imbibition protein-synthesizing capacity rises rapidly, lagging about 10
      minutes behind water uptake. This rise in synthesizing capacity is accompanied by
      an increase in polysome content. As imbibition continues, both protein
      synthesizing capacity and polysome content increase. With embryos from aged seed,
      the rate of protein synthesis is initially limited by another, presumably
      nonribosomal, reaction.

PMID- 16656381
TI  - The influence of growth regulating substances on the development of enhanced
      metabolic rates in thin slices of beetroot storage tissue.
AB  - Freshly cut disks of beetroot tissue develop high rates of respiration, uptake of
      phosphate and activity of the enzyme invertase after having been washed for 18
      hours in 0.01 m potassium maleate.Incubation of the disks in solutions of indole
      3-acetic acid or kinetin completely prevented the development of the higher
      activities in all 3 systems assayed, while incubation in gibberellic acid had no
      inhibitory effect. Using a series of synthetic plant growth regulating compounds
      it was possible to establish that there was no correlation between the activity
      of the compound as an auxin and the ability of the compound to prevent the
      development of the enhanced rates of metabolism.

PMID- 16656382
TI  - Increase of Mitochondrial Fraction in Sweet Potato Root Tissue after Wounding or
      Infection with Ceratocystis fimbriata.
AB  - The acid-insoluble nitrogen content, lipid content, and cytochrome oxidase
      activity in the mitochondrial fraction are found to increase during incubation of
      slices of sweet potato (Ipomoea batatas) root tissue. These increases appear to
      be related to an increase in the number of the mitochondrial particles. The
      increase in the mitochondrial fraction is not accompanied by an increase in cell
      number. The nitrogen content in the mitochondrial fraction increases prior to the
      changes in the activity of cytochrome oxidase and lipid content. The increase in
      the numbers of the mitochondrial particles lags behind the increase in the
      cytochrome oxidase activity. Such findings are also found in the tissue infected
      by Ceratocystis fimbriata.The respiratory increase in response to wounding and
      infection appears to be a result of an increase in mitochondrial particles.

PMID- 16656383
TI  - Root environment acidity as a regulatory factor in ammonium assimilation by the
      bean plant.
AB  - Previous experiments have revealed a much greater efficiency of ammonium
      utilization by bean plants (Phaseolus vulgaris L.) when the acidity of the
      ambient medium was maintained at near-neutral conditions with carbonates or
      hydroxides. The present investigation, in which (15)N-labeled ammonium was used,
      permitted an assessment of the origin of nitrogen in tissue nitrogen pools with
      and without acidity control (CaCO(3) treated and untreated, respectively) in the
      root environment. Control of acidity resulted in greater ammonium uptake and
      greater incorporation into the amino fraction, amide, and ethanol-insoluble
      nitrogen by the root tissue. These differences were clearly evident by the fifth
      day after ammonium nitrogen had been applied.Shoots of the untreated plants
      rapidly accumulated free ammonium and amino nitrogen. A substantial portion of
      both fractions came from pre-existing nitrogen in the plants, indicating
      significant protein degradation. No evidence was found for such degradation in
      the roots of the untreated plants or in either roots or shoots of CaCO(3) treated
      plants. The data indicate that control of ambient acidity in the root environment
      during ammonium absorption enhanced the conversion of entering ammonium to
      organic nitrogen compounds in the root tissue thereby restricting movement of
      free ammonium to shoots. Consequently, the detrimental effects of high ammonium
      concentrations in the leaves were largely prevented.

PMID- 16656384
TI  - Partial purification and kinetics of indoleacetic Acid oxidase from tobacco
      roots.
AB  - Extracts from roots of Nicotiana tabacum L var. Bottom Special contain oxidative
      enzymes capable of rapid degradation of indoleacetic acid (IAA) in the presence
      of Mn(2+) and 2, 4-dichlorophenol. Purification of IAA oxidase was attempted by
      means of ammonium sulfate fractionation and elution through a column of SE
      Sephadex. Two distinct fractions, both causing rapid oxidation of IAA in the
      absence of H(2)O(2), were obtained. One fraction exhibited high peroxidase
      activity when guaiacol was used as the electron donor; the other did not oxidase
      guaiacol. Both enzyme fractions caused similar changes in the UV spectrum of IAA;
      absorption at 280 mmu was reduced, while major absorption peaks appeared at 254
      and 247 mmu. The kinetics of IAA oxidation by both fractions were followed by
      measuring the increase in absorption at 247 mmu. The peroxidase-containing
      fraction showed no lag or a slight lag which could be eliminated by addition of
      H(2)O(2) (3 mumoles/ml). The peroxidase-free fraction showed a longer lag, but
      addition of similar amounts of H(2)O(2) inhibited the rate of IAA oxidation and
      did not remove the lag. With purified preparations, IAA oxidation was stimulated
      only at low concentrations of H(2)O(2) (0.03 mumole/ml). A comparison of K(m)
      values for IAA oxidation by the peroxidase-containing and peroxidase-free
      fractions suggests that tobacco roots contain an IAA oxidase which may have
      higher affinity for IAA and may be more specific than the general peroxidase
      system previously described from other plant sources. A similar oxidase is
      present in commercial preparations of horseradish peroxidase. It is suggested
      that oxidation of IAA by horseradish peroxidase may be due to a more specific
      component.

PMID- 16656385
TI  - Substitution of germanium for boron in plant growth.
AB  - The observation was confirmed that the addition of germanium dioxide (soluble
      form) to the nutrient solution can delay for a short time the appearance of boron
      deficiency symptoms on the shoots of sunflower plants (Helianthus annuus L.).
      This appeared to be true, however, only under growing conditions in which the
      plants had a low boron requirement. The delay in the appearance of boron
      deficiency symptoms by administering germanium was demonstrated in sunflower
      plants ranging in age from 7 to 20 days. This effect was noted whether the
      germanium was administered prior to or at the time the plants were transferred to
      minus-boron nutrient solution.It is proposed that germanium does not truly
      substitute for boron in metabolic processes of the plant but rather functions
      through increasing the mobility of soluble boron within the plant and in binding
      nonmetabolic polyhydroxyl sites thus serving in a sparing role for the limited
      quantity of soluble boron in the growth centers.

PMID- 16656386
TI  - Experimental biology of ammonia-rich environments. Germination of allium seed, a
      novel capability among angiosperms.
AB  - Seed populations from a majority of species and cultivars of Allium yield up to
      15% germination under atmospheres containing NH(3) together with equal volumes of
      N(2) or air. Selected onion and leek cultivars tested in a range of NH(3) or O(2)
      compositions show little or no dependency upon quantitative variations in these
      gases.Radicles from seeds germinated in ammonia displayed low frequencies of
      abnormal mitotic activity. Comparisons of NH(4)OH with other bases, and with
      salts indicated that seed behavior could not be accounted for solely by osmolar
      or alkaline factors.Aspects of NH(3) toxicity, tolerance and permeation were also
      considered.

PMID- 16656387
TI  - Amino Acid and protein metabolism in bermuda grass during water stress.
AB  - The ability of Arizona Common and Coastal Bermuda grass [Cynodon dactylon (L.)
      Pers.] to synthesize amino acids and proteins during water stress was
      investigated. Amino acids were continually synthesized during the water stress
      treatments, but protein synthesis was inhibited and protein levels
      decreased.Water stress induced a 10- to 100-fold accumulation of free proline in
      shoots and a 2- to 6-fold accumulation of free asparagine, both of which are
      characteristic responses of water-stressed plants. Valine levels increased, and
      glutamic acid and alanine levels decreased.(14)C labeling experiments showed that
      free proline turns over more slowly than any other free amino acid during water
      stress. This proline is readily synthesized and accumulated from glutamic acid.
      It is suggested that during water stress free proline functions as a storage
      compound.No significant differences were found in the amino acid and protein
      metabolism of the 2 varieties of Bermuda grass.

PMID- 16656388
TI  - Desaspidin: a nonspecific uncoupler of photophosphorylation.
AB  - The inhibitory effect of desaspidin is shown to depend on the oxidation-reduction
      state of the system investigated. The more reducing the conditions, the more
      desaspidin-inhibited the system and vice versa.The effect of desaspidin on
      noncyclic photophosphorylation induced by TPN(+), ferricyanide or DPIP is shown
      to be due to an uncoupling action.The decrease in effectiveness of desaspidin
      under oxidizing condition is shown to depend upon a photooxidation catalyzed by
      photosystem I of chloroplasts, which is prevented, but not reversed, by the
      presence of reducing agents, such as ascorbate + DPIP.These results are
      interpreted as indicating that, contrary to previous suggestions, desaspidin is a
      nonspecific uncoupler of all types of photophosphorylation.

PMID- 16656389
TI  - Photo-oxidation of desaspidin sensitized by chlorophyll.
AB  - The uncoupler desaspidin is labile in the presence of oxidants at alkaline pH
      values. It also undergoes chlorophyll-sensitized photooxidation at a more acid
      pH. The products of the oxidation appear to have negligible activity in
      inhibiting electron transfer and photophosphorylation.Failure of desaspidin to
      uncouple in the presence of oxidants used as cofactors of noncyclic electron flow
      is presumably the result of this irreversible degradation of the desaspidin
      molecule during the early minutes of illumination or preincubation.

PMID- 16656391
TI  - Rapid Destruction of the P(FS) Form of Phytochrome by a Substance in Extracts of
      Pisum Tissue.

PMID- 16656390
TI  - Desaspidin and CO(2) Fixation by Spinach Chloroplasts.

PMID- 16656393
TI  - Effect of Electrolytes on Differentiation in Achlya sp.
AB  - Some factors controlling the differentiation of sporangia and gemmae in an
      isolate of Achlya sp. were investigated by replacement culture technique. Factors
      in the replacement medium which affect differentiation were as follows: A)
      Calcium is required for the differentiation of both sporangia and gemmae. B)
      Calcium cannot be replaced by magnesium, potassium or sodium. C) Gemmae are
      induced when the replacement medium contains salt at 40 to 80 mm. D) The salt
      induction of gemmae is nonspecific, sodium, potassium, magnesium and calcium
      chlorides are equally effective.

PMID- 16656394
TI  - Reduction of alpha-amylase by an inhibitor from carob.
AB  - Inhibitor C, one of the inhibitory fractions of the extract of Carob fruit,
      reduces the amount of alpha-amylase in the culture medium of endosperm halves of
      barley seed which have been treated with gibberellic acid as compared with seed
      halves treated with gibberellic acid alone. A similar reduction is found in the
      alpha-amylase produced by embryo halves of barley seed which have not been
      treated with gibberellic acid.

PMID- 16656395
TI  - Stomata and transpiration of droopy potatoes.
AB  - A diploid potato (Solanum tuberosum) mutant called droopy wilts easily. Excised
      leaves of the mutant lost weight, and hence water, more rapidly and had many more
      open stomata than leaves of a normal sibling. Further, the stomata of abnormal
      plants remained open in wilted leaves. When the stomata of the abnormal mutant
      were closed by a chemical spray, its excised leaves lost water no more rapidly
      than normal. Thus, the wilting of the mutant must be caused by wide stomata. The
      wilting of the abnormal leaves and the small dry weight of the plants indicate
      the advantage of the stomatal hydrostat in the normal plants.

PMID- 16656396
TI  - Glycolic Acid Labeling During Photosynthesis with CO(2) and Tritiated Water.
AB  - Chlorella pyrenoidosa were allowed to photosynthesize for short periods of time
      in the presence of (14)CO(2) and HTO. Analysis of tritium and (14)C labeling of
      photosynthetic intermediate compounds showed that the T/(14)C ratio of glycolic
      acid was comparable to that of intermediate compounds of the photosynthetic
      carbon reduction cycle when photosynthesis was performed in nearly 100% oxygen
      and only slightly higher under steady-state conditions. It is concluded that
      formation of labeled glycolic acid as a consequence of its proposed hydrogen
      transport role in photosynthesis is quantitatively of limited importance compared
      to the net synthesis of glycolic acid from CO(2).

PMID- 16656397
TI  - Relationship of Phenylalanine Ammonia-lyase Activity to o-Hydroxycinnamic Acid
      Content in Melilotus alba.
AB  - Phenylalanine ammonia-lyase activity was investigated in preparations
      representing various parts of sweetclover (Melilotus alba Desr.) plants of CuCu
      and cucu genotypes. In contrast to other plant parts, very young leaves and stems
      of CuCu plants displayed high phenylalanine ammonia-lyase activity. Initial leaf
      samples from CuCu plants were approximately 3 times as high in enzyme activity as
      leaves from cucu plants, but stems were only slightly higher in activity.
      Defoliation of the plants resulted in decreased enzyme activity, increased o
      hydroxycinnamic acid content, and essentially no difference in enzyme activity
      between the genotypes. It appears that phenylalanine ammonia-lyase activity in
      leaves is not primarily controlled by the Cu/cu alleles and that the reaction
      catalyzed by this enzyme is not the limiting step in o-hydroxycinnamic acid
      synthesis.

PMID- 16656398
TI  - Changes in Fatty acids of alfalfa roots during cold hardening.
AB  - The fatty acid composition of nonhardy Caliverde and hardy Vernal alfalfa roots
      as a function of the hardening process was determined by gas-liquid
      chromatography.The fatty acid contents of nonhardy Caliverde and hardy Vernal
      alfalfa root tissue increased approximately 2-fold during hardening. This
      increase was associated with hardening but could not be used to distinguish
      between varieties. The fatty acid composition of the alfalfa root changed during
      hardening due to the preferential accumulation of polyunsaturated fatty acids.
      The preferential deposition of linoleic and linolenic fatty acids caused an
      increase in the average number of unsaturated bonds in the fatty acids.
      Apparently, lipid metabolism of the roots was altered during hardening.

PMID- 16656399
TI  - The chromophore of phytochrome.
AB  - The chromophore of phytochrome, the plant photomorphogenic pigment, was cleaved
      from the associated protein. Chromatographic and spectral properties indicated
      that it was a bilitriene closely similar to but distinct from the chromophore of
      C-phycocyanin and allophycocyanin.

PMID- 16656400
TI  - Biosynthesis of s-methylcysteine in radish leaves.
AB  - Investigation on the biosynthesis of S-methyl-L-cysteine in radish leaves has
      shown that it is formed by the methylation of cysteine. This conclusion is based
      on: A) the relatively high recovery of radioactivity in methylcysteine sulfoxide
      after the administration of cysteine or methyl-labeled methionine to radish
      leaves; B) the nearly complete recovery of label from methyl-labeled methionine
      in the methyl group of methylcysteine sulfoxide; and C) the similarity in the
      ratio of tritium to (14)C in methylcysteine sulfoxide and in its methyl group to
      this ratio in the methyl group of methionine given to radish leaves. Direct
      evidence for the synthesis of methylcysteine in radishes was obtained for the
      first time.Conclusive evidence against the formation of methylcysteine from
      serine and a thiomethyl group from methionine as suggested for garlic was the
      more efficient incorporation of the methyl group of methionine as compared to the
      sulfur atom into methylcysteine sulfoxide.

PMID- 16656401
TI  - Studies on growth regulators. I. Improved Avena coleoptile elongation test for
      auxin.
AB  - A modified procedure is presented for the bioassay of auxin using Avena
      coleoptile segments. The modifications introduced result in a substantial
      improvement of the commonly used coleoptile elongation tests.The proposed test
      retains the simplicity of physical requirements and of manipulation
      characteristic of all elongation tests. The main feature of the proposed test is
      that it permits the measurement of the elongation of coleoptile segments as being
      directly proportional to the concentration rather than to the logarithm of the
      concentration of indoleacetic acid. With an accuracy and a range comparable to
      those of the standard Avena curvature test, the proposed bioassay overcomes the
      limitations for the quantitative assessment of auxin inherent in other coleoptile
      elongation tests. An additional advantage is provided by the present procedure:
      two 5 mm segments from each coleoptile can be utilized thus doubling the number
      of assays hitherto possible with a given number of coleoptiles.

PMID- 16656402
TI  - Compositional changes of douglas fir seeds during germination.
AB  - Changes in weight, water content, nucleic acids, nucleotides, carbohydrates,
      lipids, nitrogenous and phosphorus compounds in embryo and gametophyte of Douglas
      fir seeds (Pseudotsuga menziesii Franco) were studied at 6 stages of germination.
      Lipids, proteins, and reserve phosphorus compounds in the gametophyte were
      utilized for the synthesis of carbohydrates, structural components, and soluble
      compounds in the seedling.The general quantitative metabolic changes that occur
      during germination of Douglas fir seeds are comparable to those known for
      angiosperm seeds.

PMID- 16656403
TI  - Concerning the Preparation of Chloroplasts Active in Hill and Photosynthetic
      Phosphorylation Activities from Leaves of Phaseolus vulgaris.
AB  - When bean plants are cultivated under certain conditions, liberation of cell
      contents by grinding with mortar and pestle yields chloroplasts of low Hill and
      photosynthetic phosphorylation activities, while grinding in a high speed blendor
      yields active chloroplasts. The inactivity of plastids obtained with mortar and
      pestle is due to the presence of an inactivator in the homogenate. The culture
      conditions that determine whether bean leaves ground with mortar and pestle
      contain inactivator were not determined.

PMID- 16656404
TI  - Enzymes of the glyoxylate cycle in rhizobia and nodules of legumes.
AB  - The relatively high level of fatty acids in soybean nodules and rhizobia from
      soybean nodules suggested that the glyoxylate cycle might have a role in nodule
      metabolism. Several species of rhizobia in pure culture were found to have malate
      synthetase activity when grown on a number of different carbon sources.
      Significant isocitrate lyase activity was induced when oleate, which presumably
      may act as an acetyl CoA precursor, was utilized as the principle carbon source.
      Malate synthetase was active in extracts of rhizobia from nodules of bush bean
      (Phaseolus vulgaris L.), cowpea (Vigna sinensis L.), lupine (Lupinus
      angustifolius L.) and soybean (Glycine max L. Merr.). Activity of malate
      synthetase was, however, barely detectable in rhizobia from alfalfa (Medicago
      sativa L.), red clover (Trifolium pratense L.) and pea (Pisum sativum L.)
      nodules. Appreciable isocitrate lyase activity was not detected in rhizobia from
      nodules nor was it induced by depletion of endogenous substrates by incubation of
      excised bush bean nodules. Although rhizobia has the potential for the formation
      of the key enzymes of the glyoxylate cycle, the absence of isocitrate lyase
      activity in bacteria isolated from nodules indicated that the glyoxylate cycle
      does not operate in the symbiotic growth of rhizobia and that the observed high
      content of fatty acids in nodules and nodule bacteria probably is related to a
      structural role.

PMID- 16656405
TI  - Enhancement of RNA synthesis, protein synthesis, and abscission by ethylene.
AB  - Ethylene stimulated RNA and protein synthesis in bean (Phaseolus vulgaris L. var.
      Red Kidney) abscission zone explants prior to abscission. The effect of ethylene
      on RNA synthesis and abscission was blocked by actinomycin D. Carbon dioxide,
      which inhibits the effect of ethylene on abscission, also inhibited the influence
      of ethylene on protein synthesis. An aging period appears to be essential before
      bean explants respond to ethylene. Stimulation of protein synthesis by ethylene
      occurred only in receptive or senescent explants. Treatment of juvenile explants
      with ethylene, which has no effect on abscission also has no effect on protein
      synthesis. Evidence in favor of a hormonal role for ethylene during abscission is
      discussed.

PMID- 16656406
TI  - Turnover and metabolism of chlorogenic Acid in xanthium leaves and potato tubers.
AB  - The active turnover of chlorogenic acid (3-caffeoylquinic acid(3)), a major
      phenolic component of Xanthium leaves and potato tuber disks, has been
      demonstrated in these tissues. Pulse-labelling experiments with radioactive l
      phenylalanine and trans-cinnamic acid as well as direct feeding experiments with
      chlorogenic acid-(14)C labelled in the caffeoyl moiety have been employed in the
      turnover studies. The rate of turnover is calculated to be on the order of 50 to
      100 mmumoles per hour per gram fresh weight of tissue.In Xanthium leaves
      chlorogenic acid is in part converted to an isochlorogenic acid identified by
      silica gel chromatography as 3,5-dicaffeoylquinic acid. Radioactivity of the
      caffeoyl moiety of chlorogenic acid is also incorporated into lignin-like
      insoluble polymers in the leaf. Turnover of chlorogenic acid in tuber tissue is
      largely accounted for by the incorporation of the caffeoyl moiety into insoluble
      polymers in the tissue.The significance of chlorogenic acid turnover is discussed
      in relation to the perception of the photoperiodic stimulus by leaves and to the
      possible role of chlorogenic acid in lignin synthesis.

PMID- 16656407
TI  - Effect of Photoperiodic Floral Induction on the Metabolism of a Gibberellin
      Precursor, (-)-Kaurene, in Pharbitis nil.
AB  - Pharbitis nil seedlings rapidly metabolized (-)-kaurene-17-(14)C administered to
      the cotyledons. Less than 20% of the radioactivity was recovered by extraction of
      the cotyledons on the following day. Of this the major metabolite was an
      unidentified acidic material which did not correspond chromatographically to any
      of the known gibberellins.Significant differences were observed between the
      radioactivity found in the buds of a group of seedlings subjected to
      photoperiodic floral induction and that in a noninduced group. In both cases
      almost all of this radioactivity was in the neutral fraction, but thin-layer
      chromatography of these fractions revealed that the induced group contained 2 or
      more labelled components which were either absent or present in lower
      concentrations in the noninduced group.

PMID- 16656408
TI  - Organs of gibberellin synthesis in light-grown sunflower plants.
AB  - The sites of gibberellin (GA) synthesis in light grown sunflower plants were
      studied. The results of organ excision and the exogenous application of indole
      acetic acid and gibberellic acid indicated that gibberellin synthesis occurred in
      the young leaves of the apical bud. This was substantiated using a combination of
      diffusion and extraction techniques. Diffusion of sunflower apical buds on agar
      for 20 hours revealed a level of gibberellin greater than that obtained by
      solvent extraction of a similar number of apices, indicating that synthesis of
      gibberellin was occurring in those apices during the diffusion period. The
      gibberellin level of apices extracted following a 20 hour diffusion period was
      the same as that obtained from buds extracted immediately following excision from
      the plant, again suggesting that apical buds are sites of gibberellin synthesis.
      A similar experiment was conducted with young internodal sections, the results
      indicating that they were not sites of gibberellin synthesis.The ability of
      various parts of sunflower plants to produce gibberellin as measured by the agar
      diffusion technique was correlated to internode elongation, the region of maximum
      gibberellin production being associated with the region of maximum extension
      growth.Root tips were also shown to be sites of gibberellin synthesis, this
      ability being confined to the apical 3 to 4 mm region of the root.

PMID- 16656409
TI  - Abnormal stomatal behavior in wilty mutants of tomato.
AB  - An attempt was made to explain the excessive wilting tendency of 3 tomato
      mutants, notabilis, flacca, and sitiens. The control varieties in which these
      mutations were induced are Rheinlands Ruhm for flacca and sitiens and Lukullus
      for notabilis. Although all 3 mutants are alleles of separated loci, they seem to
      react similarly to water stress. The mutants wilt faster than the control plants
      when both are subjected to the same water stress. It was demonstrated by
      measurements of water loss from whole plants that all 3 mutants have much higher
      rates of transpiration than the control varieties, particularly at night. The
      extent of cuticular transpiration was compared in both kinds of plants by
      measuring the rate of water loss from detached drying leaves coated with vaseline
      on the lower surface. The difference in cuticular transpiration between the
      mutant and the control plants seems to be negligible. However, various facts
      point to stomata as the main factor responsible for the higher rates of water
      loss in the mutant plants. The stomata of the latter tend to open wider and to
      resist closure in darkness, in wilted leaves, and when treated with
      phenylmercuric acetate. Stomata of the 2 extreme mutants, sitiens and flacca,
      remain open even when the guard cells are plasmolyzed. The stomata of the mutants
      also are more frequent per unit of leaf surface and vary more in their size.

PMID- 16656410
TI  - Inhibition of Flower Initiation in Pharbitis nil by an Inhibitor of Steroid
      Biosynthesis is Dependent on Seedling Age.

PMID- 16656411
TI  - Isozymes of alpha-Amylase Induced by Gibberellic Acid in Embryo-less Grains of
      Barley.

PMID- 16656412
TI  - Effects of Abscisin II and Other Plant Growth Substances on Germination of Seeds
      with Stratification Requirements.

PMID- 16656414
TI  - Potentiation of photosynthetic oxygen evolution in red light by small quantities
      of monochromatic blue light.
AB  - Growth of the giant unicellular green alga, Acetabularia crenulata, stops in red
      light of broad spectral composition, but can be restored by the addition of small
      quantities of blue light. Long-term records of O(2) evolution indicate that the
      photosynthesis of Acetabularia responds in a parallel manner to blue light. Cells
      photosynthesizing at a light-limited rate in white light were given red light at
      an intensity that served to match or somewhat increase the instantaneous rate of
      O(2) production. A rapid decline in the rate commenced within 15 minutes and
      continued for 2 hours or more until it had fallen to 20 to 40% of the initial
      level. Very small doses of violet or blue radiation (<10(-8) Einstein/cm(2)) then
      affected a complete, though temporary, restoration of the original rate of
      photosynthesis. Responses began after a lag of 4 to 5 minutes, regardless of
      their magnitude, and in the most favorable instances persisted 4 to 6 hours after
      the stimulus. Blue light treatments were effective as flashes as brief as 2.5
      seconds, given simultaneously or in sequence with the red measuring light, or as
      low-intensity continuous irradiations. Blue-light induction of the response was
      stable over at least 5 minutes of darkness. After a suitable red-light
      pretreatment, 2 other algae, Chlamydomonas reinhardi and Fucus vesiculosus, were
      shown to respond similarly to low-intensity irradiations with blue or blue-green
      light.Crude action spectra were determined for the response of Acetabularia to
      short wavelength irradiations given simultaneously or sequentially with the red
      measuring light. Two peaks of effectiveness were found, one near 450 mmu, and
      another, as yet ill defined, in the near UV. The data suggest a shoulder around
      490 mmu. All wavelengths above 540 mmu were entirely ineffective.

PMID- 16656415
TI  - Biosynthesis of Protein Amino Acids in Plant Tissue Culture II Further Isotope
      Competition Experiments Using Protein Amino Acids.
AB  - The behavior of exogenously supplied alanine, proline, glutamine, glutamic acid
      and aspartic acid in isotope competition experiments using cells of Paul's
      Scarlet Rose grown in the presence of glucose-U-(14)C was examined at higher
      concentrations than were used in part I of this series.Each amino acid
      contributes significantly to protein above a minimum concentration in the culture
      medium. There is, therefore, no general difference between the behavior of these
      amino acids and the behavior of the remainder of the protein amino acids in
      isotope competition experiments.At higher concentrations increasing amounts of
      carbon from the amino acids in the culture medium was found in other protein
      amino acids. Using the relative sizes of these contributions metabolic inter
      relationships for these amino acids were deduced.

PMID- 16656416
TI  - Hexose-, inositol-, and nucleoside phosphate esters in germinating seeds of
      crested wheatgrass.
AB  - Net synthesis of phosphate esters was measured in crested wheatgrass seeds
      [Agropyron desertorum (Fisch.) Schult.] to learn what phosphorylating reactions
      occur in early stages of germination. Phosphate esters were separated on ion
      exchange columns and identified by cochromatography and chemical analyses.
      Synthesis of adenosine triphosphate and UDP-hexose was detected 6 hours after the
      beginning of water absorption. This synthesis occurred during the period of rapid
      increase in water potential. Synthesis of hexose phosphate and uridine
      triphosphate was detected 12 hours after the beginning of water absorption. The
      concentrations of these esters increased during 48 hours. Increases in
      concentration of inositol di-, tri-, and tetraphosphate suggested that hydrolysis
      of inositol hexaphosphate began after 12 hours.

PMID- 16656417
TI  - A soluble fraction requirement in the transfer reaction of protein synthesis by
      rice embryo ribosomes.
AB  - The requirements for the transfer of (14)C-phenylalanine from yeast soluble
      ribonucleic acid to protein in vitro by rice (Oryza sativa L. var. Bluebonnet)
      ribosomes have been investigated. An absolute requirement for polyuridylic acid,
      2-mercaptoethanol, guanosine triphosphate, magnesium, and potassium or ammonium
      ions and ribosomes has been demonstrated. Ribosomes washed in 0.5% sodium
      deoxycholate also required the presence of rice supernatant. The optimum
      concentration of magnesium ion for the reaction was approximately 7 mm, while 60
      mm of either ammonium or potassium ion gave maximum transfer of phenylalanine in
      this heterologous system. The optimum concentration of guanosine triphosphate
      required varied with the presence or absence of the phosphoenolpyruvate-pyruvate
      kinase generating system. Without the system, the optimum concentration was 1.5
      mm, but in its presence the optimum was approximately 0.1 mm.

PMID- 16656418
TI  - Selenium nutrition of green plants. Effect of selenite supply on growth and
      selenium content of alfalfa and subterranean clover.
AB  - Alfalfa and subterranean clover plants were grown in highly purified nutrient
      solutions to which selenite selenium had been added at 0, 0.025, 0.25, 2.5 or
      25.0 mug-atoms/liter. In both species, yields of tops and roots were
      significantly less at 25.0 mug-atoms/liter than at lower selenium concentrations
      (p < 0.01). The results indicated that growth was adversely affected when the
      concentration of selenium in mature leaf tissue reached 0.2 to 0.8 mug-atom/g dry
      weight.No beneficial effect of selenium was demonstrated on the growth of either
      species. If selenium is required by these species, the critical level will
      probably be below 0.001 mug-atom/g of dry plant material. Results are discussed
      in relation to earlier work on the selenium nutrition of plants.

PMID- 16656419
TI  - Regulation of betacyanin efflux from beet root by poly-L-lysine, ca-ion and other
      substances.
AB  - Poly-l-lysine, poly-alpha, gamma-diaminobutyric acid and basic proteins cause
      efflux of betacyanin from beet root tissues to varying degrees. Membrane
      activities fall in the order: polylysine > poly-alpha, gamma-diaminobutyric acid
      > polyarginine (protamine), suggesting the importance of steric factors in side
      chain to backbone relations. It was also observed that homopolymer activity >
      heteropolymer activity, using ribonuclease and lysozyme as examples of the
      latter. Among polylysines, there appears to be an optimal chain length at a
      molecular weight equal to 50,000. Lowered activity of larger polymers is
      interpreted in terms of a diffusion barrier, the cell wall.Polylysine and Ca(++)
      exhibit competitive kinetics, and Ca(++) otherwise is far more active than other
      cations. It is assumed that polylysine displaces Ca(++) from anionic centers on
      the membrane, but cannot confer equivalent dimensional stability, rendering the
      membrane leaky. The possible role of cationic shielding in ionic stabilization of
      the membrane was also considered. The order of divalent ion activity against
      polylysine was Ca(++) > Sr(++) > Mg(++), suggesting again a specific size-fit
      relationship.

PMID- 16656420
TI  - Effect of Dinitrophenol on the Heats of Respiration of Germinating Seeds of
      Prosopis juliflora, Kochia scoparia, and Oxyria digyna.
AB  - During a 36-hour period, the rate of absorption of oxygen, respiration quotient,
      and rate of evolution of heat have been measured using seeds of Prosopis
      juliflora, Kochia scoparia, and Oxyria digyna. The results obtained in pure water
      were compared with those obtained in dilute solutions of dinitrolphenol. The data
      appear to be reproducible to +/- 10% at the end of the 36-hour period and are
      independent of the amount of seeds used, provided it was 0.05 g or less. For a
      given amount of oxygen absorbed, more heat was liberated when the seeds were in a
      dinitrophenol solution. The results permit an estimate to be made of the heat
      energy stored in oxidative phosphorylation.

PMID- 16656421
TI  - Matric potential of several plant tissues and biocolloids.
AB  - The pressure membrane apparatus was used to study the matric potential
      (imbibition pressure or moisture tension) of plant tissues and of several organic
      colloidal preparations.The moisture release curves of aqueous 2% agar, 12%
      gelatin, and filter paper were smooth parabolic curves between matric potentials
      of -0.1 and -15 bars. When logarithms of the matric potentials were plotted
      against logarithms of the moisture content, the data yielded straight lines for
      agar and filter paper.Slices of fresh tissue lost little water after 2 days in
      the apparatus at maximum pressure of 15 bars. Osmotic forces in conjunction with
      cell membranes are able to retain moisture against pressure of this magnitude.
      After the cells were disrupted by freezing and thawing, up to 90% of the original
      moisture was removed by a 15 bar pressure, with lesser amounts removed at lower
      pressures. The results gave a parabolic relationship, and straight lines could be
      fitted to log-log plots of data from potato tuber and young asparagus stem
      slices. Sections from the tips of asparagus stems held less moisture at all
      matric potentials than more basal sections.The method permits the study of the
      matric potential of tissues independently of the osmotic potential. As measured,
      however, the matric potential is a composite of matric potentials of colloidal
      substances in the protoplasm and cell walls after disruption of cells by freezing
      and mixing of the contents. The value is therefore only an approximation of the
      matric potentials occurring in the living tissues.

PMID- 16656422
TI  - Interactions of phenolic acids, metallic ions and chelating agents on auxin
      induced growth.
AB  - By growth experiments in indoleacetic acid-1-(14)C (IAA), and determination of
      the (14)CO(2) evolved, it has been shown directly that polyphenols synergize IAA
      induced growth by counteracting IAA decarboxylation. Sinapic and ferulic acids
      act like polyphenols. Endogenous polyphenols doubtless exert the same influence
      in intact plants. Monophenols stimulate the decarboxylation of IAA under
      conditions where they depress growth. When Mn(++) is present as well, this effect
      is enhanced. All these growth effects are paralleled by effects on the isolated
      IAA oxidizing enzyme of Avena.EDTA acts like the polyphenols in depressing the
      decarboxylation of IAA, and not synergizing with the growth induced by
      naphthalene-acetic acid (NAA) and 2,4-D. However, since EDTA synergizes with IAA
      for growth even at optimal IAA concentrations, its growth promotion probably
      involves an additional effect.DIECA inhibits powerfully the destruction of IAA,
      but without causing much growth promotion, apparently because its decomposition
      products inhibit respiration.Mn(++) alone stimulates the decarboxylation of IAA,
      i.e. this ion promotes the IAA oxidase in vivo as it does in vitro. Nevertheless,
      it does not inhibit elongation, but at relatively high concentrations even
      stimulates it, both at low and high IAA levels. Since Mn(++) also promotes the
      growth induced by NAA and 2,4-D, its growth action cannot rest primarily on
      modifying the metabolism of the auxins.Cobalt somewhat decreases the
      decarboxylation of IAA, but this cannot explain its growth promotion, since
      Co(++), like Mn(++), stimulates elongation even at optimal IAA concentrations,
      and acts with NAA just as well as with IAA. Ferrous ion, on the other hand, acts
      like the polyphenols.Floating pea stem sections exude enough organic matter to
      support bacteria which after 7 hours cause considerable decarboxylation of IAA.
      Avena coleoptile sections have a comparable though smaller effect after 12
      hours.The present experiments, with those of others, point to a major role for
      polyphenolase in controlling hormone balance, since the introduction into a
      phenolic molecule of a second, adjacent hydroxyl group changes the action from
      auxin-destroying to auxin-preserving. Thus the phenol oxidizing enzymes must act
      as general growth controllers.

PMID- 16656423
TI  - Changes in some nitrogenous components during the germination of pea seeds.
AB  - The changes in major nitrogenous components during the germination of pea seeds
      have been followed. During the period of rapid axis growth, 3 to 8 days following
      germination, the nitrogen content of the cotyledons declines rapidly with an
      accompanying increase of nitrogen in the developing axis. The accumulation of
      alcohol soluble nitrogen, primarily amino nitrogen, in the cotyledons and axis
      during germination indicates that the mobilization of nitrogen is facilitated by
      proteolysis and translocation of the products.Pea cotyledons had an initially
      high RNA content which declined during germination while axis RNA increased. The
      increase in axis RNA was greater than the decline in cotyledonary RNA indicating
      a net nucleic acid synthesis. Thus some of initial nitrogen reserve is
      interconverted to provide for nucleic acid synthesis.During the depletion of
      cotyledonary RNA there was no accumulation of nucleotides in the cotyledons,
      nucleotide content of the axis did, however, increase during the germination
      period.The DNA content of the axis increased with growth of that organ. There was
      also an increase in DNA content of the cotyledons during the early stages of
      germination.

PMID- 16656424
TI  - Phosphorus metabolism of germinating oat seeds.
AB  - An investigation has been made of the changes in the major phosphorus containing
      substances in Avena sativa during the first 8 days of dark germination. The
      endosperm, roots, and shoots were analyzed separately for acid soluble-P, phytic
      acid-P, inorganic-P, lipid-P, nucleic acid-P, and protein-P. Phytic acid-P
      comprised 53% of the total seed phosphate, while the sum of lipid-P, nucleic acid
      P and protein-P comprised 27% of the seed phosphate. All these reserve phosphate
      materials were mobilized and transferred to the developing axis. The phosphate
      from phytic acid appeared almost entirely as inorganic-P in the roots and shoots.
      A close stoichiometry existed between the rate of loss of nucleic acid-P from the
      endosperm and its rate of appearance in the roots and shoots. Thus no net
      synthesis of nucleic acid occurred during the 8-day period examined. The rate of
      synthesis of lipid-P in the roots and shoots exceeded its rate of disappearance
      from the endosperm during the first 4 days of germination. Protein-P increased in
      the roots and shoots during germination, but at a rate less than its rate of
      disappearance from the endosperm. The results provide a relatively complete
      description of the over-all aspects of phosphorus metabolism associated with
      germination of oats.

PMID- 16656425
TI  - Fatty Acid accumulation in maturing flaxseeds as influenced by environment.
AB  - The effects of temperature and light on boll and shoot maturity and on the
      accumulation of fatty acids in developing seeds of flax (Linum usitatissimum L.)
      were determined in controlled environments. Palmitic and linoleic acids decreased
      but linolenic increased in percent as seed formation progressed. In the same
      period, oleic acid increased in percent in 1 variety and decreased in another.
      Increased temperatures hastened these changes and resulted in decreased iodine
      value of the oil at maturity.Calculated on a weight basis (mg per 1000 seeds),
      all 5 major fatty acids increased during seed formation. Increased temperatures
      initially accelerated the accumulation of all fatty acids, but the period of net
      fatty acid synthesis was eventually shortened in comparison with cooler
      temperatures. At 15 degrees and 20 degrees , linolenic acid accumulation closely
      paralleled the rate of boll maturation, measured by boll moisture content; at 30
      degrees linolenic accumulation ceased before maturation could be detected.A
      photoperiod of 20 hours accelerated plant maturity resulting in decreased seed
      weight in comparison with a photoperiod of 16 hours. Eight hour photoperiod
      favored late blossoming and depressed seed weight, oil content, and fatty acid
      content. Weights of linoleic and linolenic acids were high in both the 16 and 20
      hour photoperiods.Linolenic acid was reduced in percent and weight per 1000 seeds
      at light intensities of 1200 ft-c as compared with 2700 ft-c.

PMID- 16656426
TI  - Physiological basis of differential strontium accumulation in two barley
      genotypes.
AB  - Studies of rates of Sr transport from nutrient solutions containing 8
      concentrations of Sr indicate a definite trend towards higher rates of Sr
      transport by roots of intact 12-day-old Regal barley (Hordeum vulgare, L.)
      seedlings as compared with Tregal. Differences in rates of Sr transport between
      the 2 varieties were also indicated by higher concentrations of Sr in fluids
      exuding from decapitated Regal roots as compared to fluids exuding from
      decapitated Tregal roots.No differences between Regal and Tregal were found in
      the physical factors of distance from epidermis to endodermis, number of cortical
      cell layers, or transpiration rate. Furthermore, no relationship was observed
      between transpiration rate and rate of Sr accumulation.Dependence of Sr transport
      on metabolic processes was indicated by marked effects of temperature, cyanide,
      and dinitrophenol on rates of Sr transport. Q(10) values for Sr transport by
      Regal and Tregal approached 2, thereby indicating that metabolic reactions were
      associated with this process. Strontium transport by both Regal and Tregal was
      markedly depressed in the presence of either cyanide or dinitrophenol. These
      results led to the conclusion that the Sr transport process is dependent on
      metabolic energy derived from respiration.

PMID- 16656427
TI  - Mathematical model of polar auxin transport.
AB  - Polar auxin transport can be simulated by a model which achieves polarity through
      the preferential secretion of more auxin from the lower end than from the upper
      end of each cell. Solution of the model using a computer provides a possible
      explanation of the differences between the polarity expressed by different
      tissues and the differences between pieces of different lengths, on the basis of
      small differences in the polarity of auxin secretion from individual cells. A
      method of estimating the polarity of individual cells is described.

PMID- 16656428
TI  - Kinetics of polar auxin transport.
AB  - The movement of auxin in the basipetal and acropetal directions is compared for 4
      types of tissue. It is observed that the transport may proceed in either a linear
      or a non-linear manner with time. The polarity of transport through any given
      type of tissue increases exponentially with increasing lengths of tissue
      traversed, suggesting that the polarity of transport is developed as a
      consequence of the repeated passage through cells. Using the mathematical model
      of Leopold and Hall, the extent of polarity for individual cells is estimated,
      and a very small polarity of individual cells is found to be capable of
      accounting for the marked polarity of whole tissues. It is suggested that
      transport polarity may be functionally a property of the multicellular structure,
      being amplified from very small differences in activities at the 2 ends of
      individual cells.

PMID- 16656429
TI  - Conversion of isatin to isatate as related to growth promotion in Avena
      coleoptile and pisum stem sections.
AB  - Isatin, (indole 2,3-dione), which promotes elongation of Pisum stem sections at
      concentrations exceeding 0.1 mm, promotes elongation of Avena coleoptile sections
      only at higher concentrations, exceeding 1 mm. Aged isatin solutions are more
      active than fresh solutions, due to the slow, spontaneous conversion to isatate
      (o-aminophenylglyoxylate). A concentration of 0.1 mm aged isatin is as active in
      Avena coleoptile sections as in peas. Isatate has been independently synthesized
      and its auxin activity in both Avena coleoptile and Pisum stem sections
      confirmed. The synthetic isatate is more effective than isatin in both systems.
      This suggests that the auxin activity of isatin is due to its conversion to
      isatate.

PMID- 16656430
TI  - Inositol Metabolism in Plants. III. Conversion of Myo-inositol-2-H to Cell Wall
      Polysaccharides in Sycamore (Acer pseudoplatanus L.) Cell Culture.
AB  - Prolonged growth of cell cultures of sycamore (Acer pseudoplatanus L.) on agar
      medium containing myo-inositol-2-(3)H resulted in incorporation of label
      predominately into uronosyl and pentosyl units of cell wall polysaccharides.
      Procedures normally used to distinguish between pectic substance and
      hemicellulose yielded carbohydrate-rich fractions with solubility characteristics
      ranging from pectic substance to hemicellulose yet the uronic acid and pentose
      composition of these fractions was decidedly pectic. Galacturonic acid was the
      only uronic acid present in each fraction. Subfractionation of alkali-soluble
      (hemicellulosic) polysaccharide by neutralization followed by ethanol
      precipitation gave 3 fractions, a water-insoluble, an ethanol-insoluble, and an
      ethanol-soluble fraction, each progressively poorer in galacturonic acid units
      and progressively richer in arabinose units; all relatively poor in xylose
      units.Apparently, processes involved in biosynthesis of primary cell wall
      continued to produce pectic substance during cell enlargement while processes
      leading to biosynthesis of typically secondary cell wall polysaccharide such as 4
      0-methyl glucuronoxylan were not activated.

PMID- 16656431
TI  - Increased disease resistance and enzyme activity induced by ethylene and ethylene
      production of black rot infected sweet potato tissue.
AB  - Exposure of root tissue from a susceptible variety of sweet potato to low
      concentrations of ethylene induced a resistance to infection by Ceratocystis
      fimbriata and an increase in the activity of peroxidase and polyphenoloxidase in
      the tissue. Susceptible tissue that was inoculated with a pathogenic strain of C.
      fimbriata or a nonpathogenic strain that can induce resistance liberated more
      ethylene into closed chambers than tissue inoculated with strains that did not
      induce resistance. It is suggested that ethylene may be a stimulus that diffuses
      from infected areas into adjoining tissue to initiate metabolic changes which may
      lead to disease resistance. Polyphenol oxidase but not peroxidase activity was
      increased in slices of potato tubers and parsnip roots treated with ethylene. The
      activity of these enzymes in root tissue of carrot, radish or turnip was not
      altered by ethylene treatment.

PMID- 16656432
TI  - Role of IAA-Oxidase in Abscission Control in Cotton.
AB  - The potential role of indoleactic acid (IAA)-oxidase as an in vivo abscission
      regulating system in the cotton (Gossypium hirsutum L.) cotyledonary explant was
      investigated. Phenols (usually monophenols), which are cofactors of cotton IAA
      oxidase in vitro, accelerated abscission. Phenols (usually
      orthodihydroxyphenols), which inhibit cotton IAA-oxidase in vitro, inhibited
      abscission. Inhibition or stimulation of abscission was accomplished by phenols
      both with and without IAA. Results were similar when treatments were applied as
      lanolin pastes to the cut petiole ends or as solutions in which explants were
      submerged. An abscission accelerating phenol stimulated the decarboxylation of
      IAA-1-(14)C by explants and an abscission inhibiting phenol inhibited the
      decarboxylation of IAA-1-(14)C.The mechanism of abscission regulation by the
      phenolic compounds was concluded to involve auxin destruction via IAA-oxidase.In
      addition to the direct relationship of this study to abscission, the results
      support the more general hypothesis that IAA-oxidase acts in vivo to regulate
      auxin levels.

PMID- 16656433
TI  - Simulated Low-gravity Environments and Respiratory Metabolism in Avena Seedlings.
AB  - Using horizontal and vertical axis clinostats and sand-grown oat seedlings (Avena
      sativa), it was found that horizontal clinostat rotation at 2 rpm increased
      respiration and inorganic and organic phosphorus content of seedlings. Increased
      coleoptile geotropism and root growth are attributed to rotational nullification
      of the directional component of the gravitational stimulus. These growth
      modifications are mechanistically explicable by the relationship between plant
      metabolism and auxin concentration in these organs.

PMID- 16656434
TI  - Interaction of naphthaleneacetic Acid and kinetin in the senescence of detached
      leaves.
AB  - Kinetin and naphthaleneacetic acid were applied separately and in combination to
      excised leaf disks, localized areas of laminae, and petioles of detached leaves
      of broccoli (Brassica oleracea L., var. italica) and Xanthium (Xanthium
      pensylvanicum Wallr.). Senscence (measured as loss of chlorophyll) was strongly
      retarded by kinetin, but very slightly influenced by naphthaleneacetic acid. When
      the 2 substances were applied concurrently, the effect of kinetin was markedly
      reduced by naphthalene acetic acid. Neither interference with uptake nor
      transport of kinetin appeared to cause the reduction.In broccoli, the response to
      kinetin was as great in young leaves as in old leaves, and the reduction of the
      kinetin effect by naphthaleneacetic acid was greater in young leaves than in old
      leaves. Results indicate that the prevention of loss of critical material may be
      more significantly related to the delay of senescence by kinetin than is directed
      transport and accumulation (mobilization). Kinetin may control 2 or more events
      which contribute independently to the delay of senescence in detached leaves, and
      naphthaleneacetic acid may possibly interfere with only 1 of them.

PMID- 16656435
TI  - Dual mechanisms of ion absorption in relation to long distance transport in
      plants.
AB  - The characteristics of ion transport to the shoots of young corn seedlings were
      studied with respect to the nature of the isotherm through a wide concentration
      range, the competitive influence of closely related ions upon the transport of a
      given ion, and the influence of the counter-ion. Both with respect to (36)Cl and
      (86)Rb transport, the characteristics of the process in every way resemble uptake
      by non-vacuolate root tips wherein the plasma membrane is the only membrane
      involved in absorption, and where system 1 - of the 2 systems which can be shown
      to participate in absorption by vacuolate tissue - is the only system operative.
      Net ion uptake by the roots per se was shown to display both the high affinity
      (system 1) and low affinity (system 2) mechanisms. It is concluded that the
      symplastic theory of ion movement to the xylem is valid, and that the contention
      that system 1 operates at the plasma membrane while system 2 functions at the
      tonoplast is strengthened.

PMID- 16656436
TI  - Biosynthesis of Stachyose in Phaseolus vulgaris.

PMID- 16656437
TI  - Auxin-induced Expansion Growth in Disks of Chicory Root (Cichorium intybus).
AB  - Expansion growth in response to auxin in chicory root slices is greater than that
      reported for any other fleshy tissue. Responsiveness depends on time of harvest
      and duration of root storage.

PMID- 16656438
TI  - Germination of Phaseolus vulgaris II. Stimulation of Axis Growth by dl
      Fluorophenylalanines.

PMID- 16656439
TI  - Gibberellin-Enhanced CO(2) Release from Tryptophan-1-C-14 in Plant Apical Tissue.

PMID- 16656440
TI  - Reaction Properties of the Ascorbic Acid Oxidase from Myrothecium verrucaria.
AB  - Ascorbic acid oxidase activity in Myrothecium verrucaria extracts resulted in
      O(2) uptake exceeding 0.5 mole per mole of ascorbic acid and in CO(2) evolution.
      Measurement of oxidized ascorbic acid at completion of the reaction demonstrated
      that an average of 10% of the oxidized product disappeared. A comparison of the
      gas exchange data with the amount of ascorbic acid not accounted for indicated
      that the reaction could not be explained by independent oxidase and oxygenase
      systems. Chromatographic examination of the reaction mixtures identified l
      threonic acid. Experiments with ascorbic acid-1-(14)C showed that C-1 was
      partially decarboxylated during the oxidation. Test of the fungal extracts for
      enzymes that might explain the deviation from expected stoichiometry showed that
      phenolase, glutathione reductase, cytochrome oxidase, peroxidase and oxalic
      decarboxylase were not involved. Addition of azide in concentrations sufficient
      to block catalase increased excess O(2) consumption about 65%. No enzymes were
      found that could directly attack oxidized ascorbic acid. H(2)O(2) accumulated
      during oxidation in azide-blocked systems.The O(2) excess could be explained by
      assuming the enzyme had peroxidative capacity on a reductant other than ascorbic
      acid. An intermediate of ascorbic acid oxidation appeared to function as the
      substrate yielding CO(2) and l-threonic acid on degradation. The increase in
      excess O(2) utilized in azide-blocked systems and the H(2)O(2) accumulation also
      were explained by the proposed scheme.Another interpretation would involve
      production of free radicals during ascorbic acid oxidation. Evidence for this was
      the ability of extracts to oxidize DPNH in the presence of ascorbic acid. Oxygen
      radicals formed in such reactions were considered possible agents of degradation
      of ascorbic acid.

PMID- 16656441
TI  - Auxin activity of substituted benzoic acids and their effect on polar auxin
      transport.
AB  - Six dichloro-, 3 trichloro-, 2 triiodo-, and 3 heterosubstituted benzoic acids
      (amiben, dinoben, dicamba), and N-1-naphthylphthalamic acid have been tested for
      effects on growth and on polar auxin transport. Growth activity with and without
      kinetin was measured by effects on fresh and dry weights of 30-day cultures of
      fresh tobacco pith. Transport inhibition was measured by following uptake and
      output of IAA-2-(14)C through 10 mm bean epicotyl sections. The distribution of
      callus growth on vascularized tobacco stem segments was also observed. Avena
      first internode extension assays established the relative activities: dicamba >
      amiben > dinoben suggested by pith growth results. Growth effects of active
      compounds were similar with and without kinetin, except that amiben was less
      active with kinetin, while 2,3,6-trichlorobenzoic acid was more active with
      kinetin than alone. The weak auxin activity of NPA was confirmed. Transport
      experiments showed that NPA was the most inhibitory compound tested, followed by
      TIBA. Other compounds tested were at least 300 times less inhibitory to IAA
      transport. The best growth promoters were the least inhibitory to transport, and
      the most effective transport inhibitors were at best poor auxins. It is suggested
      that the weak auxin and auxin synergistic activity of TIBA (and perhaps 2,3
      dichlorobenzoic acid) in extension growth tests arises from its inhibition of
      transport of endogenous or added auxin out of the sections, rather than from its
      intrinsic auxin activity. Chemically induced apolar callus growth on vascularized
      tobacco stem explants can arise from inhibition of native auxin transport, apolar
      growth stimulation by auxinic action of the test compound, or both.

PMID- 16656442
TI  - Investigations on the Role of Boron in Plants III. Anatomical Observations.
AB  - Electron microscopic examination of leaf mesophyll cells of boron-deficient
      sunflower plant reveals that chloroplasts degenerate and cell walls undergo
      profound structural changes before any visual deficiency symptoms become
      apparent. Mitochondria, which increase in number as deficiency develops,
      frequently show myeline figures, while nuclei may develop dense rhombohedral
      structures.

PMID- 16656443
TI  - Changes in amino Acid content of excised leaves during incubation I. The effect
      of water content of leaves and atmospheric oxygen level.
AB  - Excised leaves were incubated at various water contents to determine the effect
      of water status on amino acid composition. Considerable proteolysis took place
      during incubation with a resultant increase in each amino acid in the non-protein
      fraction. However, serine, proline, gamma-aminobutyric acid and methyleysteine
      sulfoxide were the only amino acids in which there was an accumulation (i.e., net
      synthesis). Serine showed a small but consistent accumulation lasting for 6 days.
      Proline showed a greater accumulation but this ceased after 2 days.To learn more
      about the control of the proline accumulation during wilting, turgid and wilted
      leaves were incubated under aerobic and anaerobic conditions. The amino acid
      analyses showed that turgid leaves did not accumulate proline and that proline
      and methylcysteine sulfoxide accumulation was abolished by anaerobiosis. With
      other amino acids, relative concentration changes between wilted and non-wilted
      leaves were less striking than the difference between aerobic and anaerobic
      conditions.Under anaerobic conditions there was an increase in alanine and a
      large increase in gamma-aminobutyric acid which were not evident in air. Serine,
      aspartic acid, glutamic acid, and glutamine disappeared more rapidly and glycine
      disappeared less rapidly under anaerobic than under aerobic conditions.On the
      basis of these results, several pathways of amino acid degradation were
      suggested.

PMID- 16656444
TI  - Changes in Amino Acid Content of Excised Leaves During Incubation. III. Role of
      Sugar in the Accumulation of Proline in Wilted Leaves.
AB  - A previously reported accumulation of proline in wilted turnip leaves has been
      observed in 6 additional species representing 5 different families. The results
      of experiments on the conditions affecting the behavior of proline in wilted
      leaves were interpreted to mean that the supply and metabolism of available
      carbohydrate was essential for proline accumulation.The role of sugar in proline
      accumulation was determined by incubating wilted leaves with different levels of
      carbohydrate (produced either by variations in conditions of preillumination or
      by infiltration with sucrose). The results showed that proline accumulation was
      greater and most prolonged in wilted leaves with higher sugar and starch
      contents. No proline accumulation was observed in unwilted leaves. Also some
      inhibitors of glycolysis and of the tricarboxylic acid cycle prevented proline
      accumulation in wilted leaves.Based on these results, the interpretation of the
      role of sugar in proline accumulation is that the oxidation of sugars furnishes
      alpha-ketoglutarate and NAD(P)H for proline synthesis in wilted leaves.

PMID- 16656445
TI  - Effect of hydrolytic enzymes on the photosynthetic efficiency and morphology of
      chloroplasts.
AB  - Both lipase from runner beans and a protease (pronase) initially cause increased
      intensity dependence of the DCPIP Hill reaction of spinach chloroplasts. This is
      followed by an increase in the extrapolated zero intensity quantum requirement.
      Pronase treatment of the chloroplasts causes rapid changes in absorption and ORD
      spectra, whereas the effect of lipase treatment is much less pronounced. Long
      treatments of the thylakoids with the lipase and protease cause unique
      morphological changes within the membrane. These changes are used to assign
      chemical compositions to some of the structures revealed by freeze-etching.

PMID- 16656446
TI  - Contracted state as an energy source for ca binding and ca + inorganic phosphate
      accumulation by corn mitochondria.
AB  - An investigation has been made of the possibility of utilizing the potential
      energy of the contracted state of corn mitochondria to drive Ca + inorganic
      phosphate accumulation. Contraction was obtained with succinate or NADH
      oxidation. In the succinate experiments the mitochondria were contracted in
      buffered KCl layered over sucrose in centrifuge tubes and centrifuged down
      through distinct wash, reactive and isotope exchange layers. In the NADH
      experiments, ion accumulation was initiated upon exhaustion of the substrate. The
      results show that mitochondria in the contracted state will actively bind some
      (45)Ca, but no real accumulation occurs until inorganic phosphate is available.
      Substrate powered contraction in the presence of inorganic phosphate also
      provides a potential for accumulation upon subsequent reaction of the
      mitochondria with Ca. It is deducted that contraction is due to X approximately I
      formation, to which Ca will bind. Subsequent reaction with inorganic phosphate
      produces CaX approximately P, which is the transport moiety. When X approximately
      P is formed first, Ca also reacts to produce CaX approximately P. Hence it is
      immaterial which ion reacts first with the contracted state. Contraction is
      believed to result from the action of a mechanoenzyme, presumably I approximately
      . The stability of CaX approximately I must be low for the mitochondria swell
      very rapidly upon exhaustion of NADH or blocking of succinate oxidation by
      cyanide.

PMID- 16656447
TI  - Ontogenetic changes in respiratory pathways in cortland apple skin during
      storage.
AB  - Ontogenic changes in respiratory pathways of skins of detached apple fruits were
      measured during a 4 month period. Results showed that an increase in pentose
      pathway occurred with increasing senescence in this tissue. Variation in
      temperature at any given age did not result in an alteration of the C(6)/C(1)
      ratio. CO(2) evolution from the pentose pathway in senescent fruit was directly
      related to O(2) uptake. Glucose uptake increased with increasing senescence
      indicating a change in cell permeability.

PMID- 16656448
TI  - Non-existence of an optimum leaf area index for the production rate of white
      clover grown under constant conditions.
AB  - Single clover plants were grown in the vegetative state, at 20 +/- 1 degrees , 85
      +/- 5% relative humidity, 320 +/- 10 ppm CO(2), 12-hour day, with Hoagland
      nutrient in Perlite, and 100 w . m(-2) of photosynthetically active radiation
      (0.4-0.7 mu) from mercury-fluorescent lamps. Each plant was confined within a
      circle 18 cm in diameter by means of a wire framework. The CO(2) exchange rate of
      the whole plant was measured every second day for 3 months. There was no optimum
      leaf area index for the net photosynthesis rate. The respiration rate was
      determined mainly by the gross photosynthesis rate and only partly by the amount
      of non-photosynthetic or heavily shaded tissue. At the maximum leaf area index,
      when leaves were dying as fast as they were being produced, both photosynthesis
      and respiration remained at or near their maximum rates. At the end of 3 months,
      the whole plant was harvested and the dry weight and carbon content determined.
      The measured dry weight was close to that calculated from the total CO(2) uptake
      and a constant ratio of carbon content to dry weight of 39%. Optimum leaf area
      indices observed in field experiments are attributed to the failure to include
      the material which dies between harvests, and to decreases in the gross
      photosynthesis rate caused by climate changes or lack of nutrient, for example.
      The difference between production rate and growth rate or yield is emphasized.

PMID- 16656449
TI  - Increased rate of net photosynthetic carbon dioxide uptake caused by the
      inhibition of glycolate oxidase.
AB  - There is considerable variation among species in their rate of photorespiration,
      and photorespiration increases greatly at higher temperatures. The addition of an
      inhibitor of glycolate oxidase, alpha-hydroxy-2-pyridinemethanesulfonic acid, to
      tobacco leaf disks at 35 degrees stimulated photosynthetic (14)CO(2) uptake at
      least 3-fold, but (14)CO(2) uptake was not changed by the inhibitor at 25 degrees
      . The inhibitor did not increase photosynthesis in maize leaf disks at either
      temperature.The evolution of CO(2) from glycolate was greatly enhanced in tobacco
      at 35 degrees compared with 25 degrees . Labeling of the glycolate of tobacco
      with glycolate-1-(14)C and -2-(14)C showed that the increased CO(2) evolved in
      the light (photorespiration) arose specifically from the carboxyl-carbon atom of
      glycolate. Maize, a species known to have a negligible photorespiration, produced
      (14)CO(2) poorly from glycolate-1-(14)C in comparison to tobacco.Acetate-1-(14)C,
      a substrate metabolized by dark respiration, produced similar amounts of
      (14)CO(2) in the light in both tobacco and maize. This respiration was changed
      little relative to photosynthesis by increasing temperature.Most plants, such as
      tobacco, have a high photorespiration. The loss of fixed carbon causes an
      increase in the internal concentration of CO(2) especially at higher
      temperatures, and results in a lower CO(2) concentration gradient and therefore a
      lower net photosynthetic CO(2) uptake. Some species, like maize, have a
      negligible photorespiration and are thus more efficient photosynthetically. The
      use of an inhibitor of the oxidation of glycolate, the substrate for
      photorespiration, changed tobacco so that it behaved photosynthetically like
      maize. Thus high rates of photorespiration may limit the net CO(2) uptake in many
      plant species.

PMID- 16656450
TI  - Metabolism of tryptophan in petioles of coleus.
AB  - Auxin precursors retard abscission when applied to debladed petioles of Coleus
      blumei Benth. The d and l forms of tryptophan are equally effective in retarding
      abscission. Tryptamine is more effective than is tryptophan. Both compounds
      apparently are converted to auxin through an aldehyde intermediate. The evidence
      presented suggests that a major pathway of tryptophan metabolism proceeds through
      tryptamine, as can be demonstrated by the use of amine oxidase inhibitors in the
      petiole tissue. Cell free preparations of the tissues metabolize tryptophan-1
      (14)C with the release of carbon dioxide. The rate of tryptophan mtabolism in
      abscission tissue is 5 times that in distal petiole tissue. Radioactivity is
      associated with basic indole conversion products as well as with neutral and
      acidic fractions. The radioactivity is most concentrated in the neutral fraction.
      The results indicate that the Coleus petiole itself is capable of producing
      auxin.

PMID- 16656451
TI  - Photosynthetic Electron Transport Chain of Chlamydomonas reinhardi. IV.
      Purification and Properties of Plastocyanin.
AB  - The copper protein plastocyanin has been found to be an essential component of
      the photosynthetic electron transport chain of Chlamydomonas reinhardi, and in
      this paper we describe a method for its isolation and purification from the wild
      type strain. In addition, we describe some of its properties and compare them
      with those reported for spinach plastocyanin.The plastocyanin was extracted from
      acetone powders prepared from intact cells, and it was purified by ion exchange
      chromatography on DEAE cellulose and gel filtration on Sephadex G-75. The yield
      of the purified protein ranged from plastocyanin equivalent to 2.0 to 2.5 mug
      atoms copper per 1000 mumoles chlorophyll. In general the absorption spectrum of
      plastocyanin from C. reinhardi resembled that of the plastocyanin from spinach.
      Some spectral differences were found in the ultraviolet region where, in contrast
      to spinach plastocyanin, that of C. reinhardi had a greater absorbance (relative
      to peaks in the visible) and less evidence for phenylalanine fine structure. The
      normal oxidation-reduction potential of C. reinhardi plastocyanin was found to be
      + 0.37 volts, the same as reported for spinach plastocyanin. The molecular weight
      of C. reinhardi plastocyanin has been estimated to be 13,000 +/- 2000. In
      contrast, the value for spinach plastocyanin has been found to be 21,000.

PMID- 16656452
TI  - Photosynthetic Electron Transport Chain of Chlamydomonas reinhardi. V.
      Purification and Properties of Cytochrome 553 and Ferredoxin.
AB  - Cytochrome 553 and ferredoxin were isolated and purified from acetone powders
      prepared from intact cells of the wild-type strain of Chlamydomonas reinhardi.
      Purification was achieved by ion exchange chromatography on DEAE cellulose and
      gel filtration on Sephadex G-75.Cytochrome 553 could be oxidized with postassium
      ferricyanide and reduced with sodium ascorbate. The absorption maxima of the
      cytochrome in reduced form were found to be alpha-band 552.5 nm, beta-band 522.5
      nm, and Soret band 416.5 nm. The normal redox potential was +0.37 volt, and the
      molecular weight was estimated to be 12,000 +/- 2000. The cytochrome closely
      resembled that of the c-type cytochromes extracted from Euglena and Porphyra.
      When cultures were harvested after they had entered stationary phase, the
      cytochrome could be extracted in soluble form, and in some cases a yield of one
      cytochrome per 1000 chlorophyll molecules could be obtained.Ferredoxin showed
      absorption maxima at 278, 330, 420 and 460 nm. Thus it resembles the ferredoxin
      extracted from spinach. The molecular weight of the ferredoxin was estimated to
      be 15,000 +/- 2000.

PMID- 16656453
TI  - Photosynthetic Electron Transport Chain of Chlamydomonas reinhardi VI. Electron
      Transport in Mutant Strains Lacking Either Cytochrome 553 or Plastocyanin.
AB  - A mutant strain of Chlamydomonas reinhardi, ac-206, lacks cytochrome 553, at
      least in an active and detectable form. Chloroplast fragments of this mutant
      strain are inactive in the photoreduction of NADP when the source of electrons is
      water, but they are active when the electron source is 2,6
      dichlorophenolindophenol and ascorbate. The addition of either cytochrome 553 or
      plastocyanin, obtained from the wild-type strain, has no effect upon the
      photosynthetic activities of the mutant strain. Cells of the mutant strain lack
      both the soluble and insoluble forms of cytochrome 553, but they possess the
      mitochondrial type cytochrome c. Thus, the loss of cytochrome 553 appears to be
      specific.Another mutant strain, ac-208, lacks plastocyanin, or possesses it in an
      inactive and undetectable form. Chloroplast fragments of ac-208 are inactive in
      the photoreduction of NADP with either water or 2,6-dichlorophenolindophenol and
      ascorbate as electron donors. However, these reactions are restored upon the
      addition of plastocyanin. The addition of cytochrome 553 has no effect. The
      measurement of light-induced absorbance changes with ac-208 reveal that, in the
      absence of plastocyanin, light fails to sensitize the oxidation of cytochrome
      553, but it will sensitize its reduction. However, the addition of plastocyanin
      restores the light-induced cytochrome oxidation.A third mutant strain, ac-208
      (sup.) carries a suppressor mutation that partially restores the wild phenotype.
      This mutant strain appears to possess a plastocyanin that is less stable than
      that of the wild-type strain.The observations with the mutant strains are
      discussed in terms of the sequence of electron transport System II --> cytochrome
      553 --> plastocyanin --> System I.

PMID- 16656454
TI  - Effect of temperature on invertase, invertase inhibitor, and sugars in potato
      tubers.
AB  - The accumulation of reducing sugars in potato tubers exposed to low temperatures
      occurs with concomitant formation of the enzyme invertase. During the initial
      period of cold treatment when reducing sugars increase rapidly, invertase
      formation proceeds until the level of enzyme exceeds that of an endogenous
      macromolecular invertase inhibitor, resulting in a basal invertase activity. As
      the rate of sugar accumulation decreases and the sugar level becomes nearly
      constant, total invertase decreases, the basal activity disappears, and a low
      excess of inhibitor develops. On transfer of cold-stored tubers to warmer
      temperatures, sugars and invertase decrease sharply and a large excess of
      inhibitor develops. These changes in sugars, invertase and inhibitor occur
      reversibly when the tubers are subjected to alternating temperatures.

PMID- 16656455
TI  - Salt hardiness and dye reduction by potato tissue and mitochondrial fractions as
      influenced by previous storage of the tubers.
AB  - Oxygen uptake and tetrazolium reduction occurred at higher rates in discs from
      potato tubers (Solanum tuberosum L.) stored at 0 degrees than in discs from
      tubers stored at 12.8 degrees . Tetrazolium reduction was at a higher rate in
      mitochondrial fractions from tubers stored at 0 degrees than in mitochondrial
      fractions from tubers stored at 12.8 degrees . These physiological activities
      were more resistant to hypertonic KCl treatments in tissue and mitochondrial
      fractions from tubers stored at 0 degrees than in tissue and mitochondrial
      fractions from tubers stored at 12.8 degrees . Inhibition of O(2) uptake and
      tetrazolium reduction progressively increased with increasing concentrations of
      KCl for tissue and mitochondrial fractions from tubers stored at 0 and 12.8
      degrees , but inhibition was more severe and occurred at lower concentrations of
      KCl for the material from tubers stored at 12.8 degrees . Tissue from tubers
      stored at 0 degrees was at the same time more sensitive to hypotonic solutions
      and more resistant to hypertonic solutions than corresponding tissue from tubers
      stored at 12.8 degrees . Adaptive changes brought on in the tubers by the stress
      of cold storage were demonstrated in the discs and mitochondrial fractions
      prepared from cold-stored tubers.

PMID- 16656456
TI  - Effect of sink region cooling on translocation of photosynthate.
AB  - The effect of metabolic inhibition of the sink tissues on translocation of (14)C
      labeled photosynthate was studied by cooling part or all of the sink region in a
      translocating sugar beet plant (Beta vulgaris L. var Klein Wanzleben).When the
      sink region was cooled, 4 phases were observed: a temporary decline, a period of
      translocation at the pre-treatment rate, a period of decline, and a new steady
      rate at 35 to 45% of the original rate. The new rate persisted throughout 26
      hours of cooling.Cooling half the blade of a developing leaf caused a decline in
      translocation to the uncooled half. When a portion of the beet was cooled,
      translocation to a developing leaf located above the supply leaf node increased
      30%.Translocation into the treated region recovered rapidly and completely when
      cooling ceased indicating that cooling had not caused serious damage to tissues.
      Enhancement of the proportion of (14)C as sucrose in the cooled portion of the
      sink leaf as compared with the corresponding warm side indicated that sucrose is
      the chief species of translocate molecule arriving in the sink.The data suggest
      that the translocation process includes active uptake into storage and growing
      areas.

PMID- 16656457
TI  - Propionate in heme biosynthesis in soybean nodules.
AB  - When soybean nodules are incubated with propionate-2-(14)C the heme moiety of
      leghemoglobin becomes labeled. The incorporation of propionate-2-(14)C into heme
      is linear with time and it appears that propionate is utilized without a lag
      period. The rate of incorporation of propionate-2-(14)C into heme is more rapid
      than the rate of incorporation of succinate-2-(14)C and citrate-1,5-(14)C,
      however, these rates of incorporation may be influenced by different sizes of
      endogenous pools of organic acids.Additional radioactive tracer experiments
      demonstrate that the supply of heme precursors from propionate is competitive
      with the supply of heme precursors from the citric acid cycle. When the
      concentration of propionate was high in the incubation mixture, the rate of
      succinate-2-(14)C incorporation into heme was decreased. Furthermore, when a
      large amount of succinate or acetate is added to the incubation mixture
      containing whole nodules, the rate of incorporation of propionate-2-(14)C into
      heme is reduced. The data support the hypothesis that propionate utilization
      makes possible a mechanism for the formation of succinyl-CoA in addition to that
      provided by the citric acid cycle.The fact that propionate is readily utilized by
      bacteroids suggested that this compound may be a normal metabolite in nodules. No
      detectable pool of propionate was found, however, in either soybean nodules or in
      isolated bacteroids suggesting that propionate, if present, is utilized as
      rapidly as it is formed. Experiments in which cell-free extracts of nodule
      bacteroids were used demonstrated the conversion of lactate to propionate. The
      cofactor requirements for these enzymic reactions are adenosine 5-triphosphate,
      Mg(++) and reduced nicotinamide adenine dinucleotide.

PMID- 16656458
TI  - Electrophoretic and Immunological Comparisons of Soluble Root Proteins of
      Medicago sativa L. Genotypes in the Cold Hardened and Non-Hardened Condition.
AB  - Electrophoretic and immunological properties of the soluble root protein
      complement of 6 Medicago sativa L. genotypes in the cold hardened and non
      hardened physiological condition were compared. These 6 genotypes were chosen to
      represent a range of abilities to survive exposure to subfreezing temperatures
      when in the cold hardened condition.A zone of highly charged and/or low molecular
      weight protein components were found to be more prevalent in the protein
      complements of the cold-hardened material than the non-hardened
      material.Immunodiffusion plate tests were not so definitive as the
      electrophoretic patterns for identifying the genotypes or physiological
      conditions, but did corroborate the electrophoretic interpretations.

PMID- 16656459
TI  - Reversible swelling and contraction of isolated spinach chloroplasts.
AB  - By use of a micro technique for producing extracts of spinach mesophyll cells,
      chloroplasts were isolated in a state wherein they displayed microscopically
      visible, reversible osmotic properties. Swollen spherical chloroplasts treated
      with hypertonic sucrose or mannitol media, but not NaCl, could be shrunken to a
      state resembling their disk appearance in living cells. Reversible osmotic
      behavior was more easily demonstrated when the chloroplasts were initially
      isolated from cells in a relatively low osmolar concentration in contrast to
      using 0.25 m sucrose or more concentrated media. Individual chloroplasts could be
      swollen and contracted repeatedly through as many as 4 cycles. The relationship
      between the capacity for osmotic behavior and chloroplast appearance in cell
      extracts is discussed.

PMID- 16656460
TI  - Chlorophyll synthesis in chlorella I. Occurrence of a lag phase on initiation of
      a dilute culture.
AB  - A culture of Chlorella established by 30-fold dilution of a culture already grown
      to a level of 15 ml packed cell volume per liter produces little chlorophyll for
      approximately 12 hours. Investigation of other characteristics such as nitrogen
      incorporation, increase in packed cell volume and dry weight as well as RNA level
      show all of these to increase without any significant lag. alpha-Linolenate,
      which can be considered as a chloroplast marker, increased markedly.
      Photosynthetic oxygen evolution and respiration as well as the heme enzyme,
      catalase, increase also, indicating that the lag in chlorophyll synthesis is not
      due to a general inability to produce the porphyrin moiety.The lag period was
      demonstrated not to be related to a deficiency of culture elements nor to
      inhibitors produced. Neither was there a need for a conditioning period of the
      medium.It is concluded that the lag in chlorophyll synthesis is unique and that
      the reasons for it are related to the response of the cells to environmental
      conditions following dilution.

PMID- 16656461
TI  - Chlorophyll Synthesis in Chlorella II. Effect of Glucose and Light Intensity on
      the Lag Phase.
AB  - Dense cultures of Chlorella grown under our conditions contain large amounts of
      chlorophyll on a packed cell basis. Upon dilution the cells are, in effect, put
      into an environment in which light is not limiting and chlorophyll seemingly in
      excess (at least temporarily). Thus it is not economical for the cell to produce
      more chlorophyll until it is the limiting factor. It is our contention that the
      cell may sense this situation by the piling up of products such as glucose or
      starch. The observed light intensity effect which causes a stimulation of
      chlorophyll production at lowered intensities is analogous to that previously
      reported by others and is felt to be related to the rate of photosynthate
      production.Chlorophyll synthesis commences after a period of about 12 hours. Once
      it has become established, added substrate or light have a smaller effect. At 36
      hours addition of glucose stimulates growth markedly but chlorophyll production
      continues at the control rate. This suggests that the effect of substrate is not
      upon the action of an enzyme involved in the actual synthesis of the chlorophyll
      molecule. Glucose has been known to influence production of certain enzymes
      involved usually in substrate catabolism. It is quite possible that the role of
      glucose here is quite similar. The data are consistent with such an explanation.
      The substrate would have to influence the production of an enzyme in the
      magnesium branch of the biosynthetic pathway of porphyrin compounds and not in
      the portion common to both iron and magnesium porphyrins. Accordingly the lag
      period is viewed as both an inhibitory period as well as a preparatory period for
      subsequent chlorophyll synthesis.

PMID- 16656462
TI  - Effect of method of preparation on the States of chlorophyll in euglena
      chloroplast fragments as determined by fluorescence spectroscopy.
AB  - The state of chlorophyll in chloroplast fragments is affected by such factors as
      the ionic strength and pH of the suspending medium. With increasing ionic
      strength or at pH values other than neutrality, there is a decrease in the
      fluorescence yield of the form of chlorophyll with fluorescence maximum at 715 to
      736 mmu (aggregate) and an increase in the yield of the form with fluorescence
      maximum at 685 mmu (monomer). (Positions of maxima cited are for 77 degrees K.)
      These changes in yield are accompanied by modifications in absorption and
      fluorescence excitation spectra. It is also noted that these effects are similar
      to the ones brought about by pancreatic lipase, wheat germ lipase, pancreatic
      trypsin or urea. An interpretation is given which is consistent with the
      experimental data, namely, that the effects originate in conformational changes
      in the proteins to which the pigments are attached. These conformational changes
      give rise to an increase in the size of the aggregate and a decrease in the
      probability of energy transfer between the monomer and aggregates.

PMID- 16656463
TI  - Effect of red light on the phototropic sensitivity of corn coleoptiles.
AB  - The effect of red light in alteration of the phototropic sensitivity of corn
      coleoptiles (Zea mays L., cultivar Burpee Barbecue Hybrid) is investigated.
      Phototropic dosage-response curves for etiolated coleoptiles are compared with
      those for coleoptiles receiving 1 hour of continuous red light immediately prior
      to phototropic induction. In the former case, only curvature comparable to the
      first positive curvature of oat coleoptiles is obtained. There is no evidence for
      first negative curvature and only minimal second positive curvature. The
      reciprocity law proved valid for all curvatures obtained. With red light, the
      sensitivity of the first positive curvature was decreased over ten-fold and there
      was clear appearance of second positive curvature for which the reciprocity law
      was not valid. Once again there was no evidence for negative curvature. Time
      course studies indicated that within 1 hour of the beginning of red light
      treatment at 25 degrees , reactions leading to the decrease in phototropic
      sensitivity of the first positive component had gone to completion whether the
      red light was continuous or consisted of a single 1 second exposure followed by a
      1 hour dark period. An action spectrum for the red-induced change in phototropic
      sensitivity showed a marked peak near 660 mmu with a small broad shoulder between
      610 and 630 mmu, characteristic of phytochrome-mediated responses. The effect of
      red light could be fully reversed by low dosages of far-red light, but longer
      doses of far red were less effective. Large dosages of far-red light alone
      induced the same alteration in phototropic sensitivity as did red light.

PMID- 16656464
TI  - Potassium Loss and Changes in the Fine Structure of Corn Root Tips Induced by H
      ion.
AB  - The effects of H, Ca, and anaerobiosis upon loss of K to ambient solutions, upon
      changes in the fine structure, and upon the respiration of corn root tissue were
      studied. In the pH range 5.5 to 8.0 losses of K decreased with decreasing H
      concentration. Ca reduced K loss greatly in the lower part of the pH range but
      with increasing pH the effect of Ca declined. Losses of K under N(2) were much
      greater than those measured under air but the same effects of H and Ca were
      found. The effect of phosphate upon K loss was found to depend upon pH,
      temperature and the state of development of the tissue.In pure H(2)O or dilute
      HCl no obvious derangement of the fine structure of meristematic cells was found
      to occur in 3 hours above pH 4.4 except attenuation of the groundplasm. At pH 4.4
      and below, serious injury was found. The presence of CaCl(2) or NaCl in the
      treatment solution greatly ameliorated the effect of H, CaCl(2) being effective
      at minute concentration (0.01 meq per liter). NaH(2)PO(4) was without any great
      effect. Anaerobiosis at neutral pH produced severe tissue damage.In contrast to
      anaerobic treatments, aerobic treatments (pH 5.8) resulting in large losses of K
      were not accompanied by any diminution of the respiratory rate.

PMID- 16656465
TI  - Thermal Inactivation Properties of Enzymes from Typha latifolia L. Ecotypes.
AB  - Irreversible thermal denaturation experiments with 3 enzymes from Typha latifolia
      populations native to distinct thermal climates produced 3 different responses:
      (1) malate dehydrogenase was much more resistant to high temperature inactivation
      when obtained from plants native to a hot climate, (2) glutamate-oxaloacetate
      transaminase was quite resistant to thermal denaturation regardless of origin,
      and (3) aldolase was rapidly inactivated by heat regardless of origin.

PMID- 16656466
TI  - Riboflavin as Photoreceptor in the Induction of Two-dimensional Growth in Fern
      Gametophytes.

PMID- 16656467
TI  - Removal of salt from xylem sap by leaves and stems of guttating plants.
AB  - Although root pressure and guttation presumably result from a high concentration
      of salt in the root xylem, the guttation fluid is very dilute. Measurements of
      the osmotic potential of the guttation liquid and of exudates at various levels
      in guttating plants indicate that salt is removed from the xylem in the upper
      part of plants, particularly in the leaves. The concentration of salt solutions
      forced through individual leaves by an artificial root pressure has no influence
      on the osmotic potential of the guttation fluid. This suggests that leaves play
      an important role in removing salt from the xylem of guttating plants.

PMID- 16656468
TI  - Reduction of acetylene to ethylene by soybean root nodules.

PMID- 16656469
TI  - Independence of morphactin and gibberellin effects upon higher plants.

PMID- 16656471
TI  - Early effects of illumination on the activity of some photosynthetic enzymes.
AB  - Leaves of dark-grown corn (Zea mays) were illuminated for periods ranging from 3
      minutes to 12 hours. The changes in the activities of ribose-5-phosphate
      isomerase, ribulose-5-phosphate kinase, and ribulose-1,5-diphosphate carboxylase
      were followed.The activity of ribose-5-phosphate isomerase did not change
      significantly until between 12 and 24 hours of illumination. An increase in
      ribulose-5-phosphate kinase activity occurred after a lag of about 6 hours. The
      increase in carboxylase activity began after 3 minutes of illumination and
      increased until after 3 to 6 hours in the light, after which it began to decline.
      The increases in these enzymes appear to be the result of protein synthesis.

PMID- 16656472
TI  - Barley endosperm bioassay for gibberellins. I. Parameters of the response system.
AB  - Parameters of the bioassay based on the gibberellin-induced reducing sugar
      release of barley endosperm were investigated. Procedures for the rapid handling
      and processing of up to several hundred treatments without loss in sensitivity of
      the test are described, and the effects of variations in many aspects of the
      bioassay were assessed.In general, the variations in varieties, techniques,
      additives, conditions, and even gibberellins, all illustrate the stability,
      sensitivity, and adaptability of the hormone-induced response and emphasize its
      utility as a gibberellin bioassay.

PMID- 16656473
TI  - Barley Endosperm Bioassay for Gibberellins. II. Application of the Method.
AB  - The use of the modified endosperm bioassay in conjunction with techniques for
      extracting and paper chromatographing extracts, and the application of
      statistical analyses to the results, is reported. The modified procedure has not
      altered the relative response to different gibberellins, though an analysis of
      many standard curves indicates that at least 1 feature of the bioassay system is
      still uncontrolled. A comparison of this bioassay with 15 others indicates that
      the endosperm response may have wide applicability in explorations of the
      physiological effects of gibberellins.

PMID- 16656474
TI  - Carbon Dioxide Production by Dry Grain of Zea mays.
AB  - Use of the gas chromatograph and a mercury-to-glass sealed respirometer adapted
      for gas syringe sampling, allowed the rapid, accurate characterization of CO(2)
      evolution rates from live and from dead-sterile Zea mays L. grain dried to
      moisture levels of 12.6 to 1.4%. The live grain at the lowest moisture level
      showed an elevated rate inconsistent with the exponential increase in rate of
      CO(2) evolution with increasing moisture found for maize with moisture contents
      from 4 to 12.6%. At the lowest moisture level, rates of CO(2) evolution from dead
      sterile grain were greater than for live grain. Moisture had no effect on CO(2)
      evolution from dead-sterile grain. Increasing temperature and increasing levels
      of O(2) in the storage atmosphere resulted in increased rates of CO(2) evolution
      from both live and dead-sterile maize. CO(2) production rates from live and from
      dead-sterile grain decreased with increasing storage time, even though
      respirometer CO(2) concentrations were less than 1% at the end of the experiment.
      Our results indicate that CO(2) production is not a dependable measure of
      respiration in dry seeds. Other experiments indicate that oxygen absorption also
      is not reliable in maize grain.

PMID- 16656475
TI  - An acetaldehyde dehydrogenase from germinating seeds.
AB  - An acetaldehyde dehydrogenase from germinating peanut cotyledons has been
      purified and its properties have been studied. At the highest purification
      achieved the preparation is free of alcohol dehydrogenase activity.The enzyme is
      specific toward diphosphopyridine nucleotide, and can oxidize a variety of
      aldehydes. The highest reaction rate is obtained with acetaldehyde, which is
      oxidized to acetate. All the attempts to demonstrate the formation of an energy
      rich acetyl derivative during the course of the reaction failed. The enzyme is
      inhibited by aldol; it is sensitive toward sulfhydryl reagents, including
      arsenite. Reduced glutathione stabilizes the enzyme, while cysteine,
      mercaptoethanol, and coenzyme A are inhibitory.Acetaldehyde dehydrogenase is
      activated by phosphate and inhibited by fatty acyl-CoA derivatives. It appears to
      be activated by the substrate, as was deduced from the shape of the plot of
      reaction velocity against acetaldehyde. These properties suggest that the enzyme
      is an allosteric protein.The plot of reaction velocity against substrate
      concentration is anomalous. The shape of this plot seems to reflect the presence
      of 2 different enzymatic activities, one with extremely high apparent affinity
      for acetaldehyde. The 2 activities may reflect 2 conformational states of a
      single enzyme or 2 separate enzymes.Experiments with tissue slices indicate that
      the reaction catalyzed by this enzyme is a step in the oxidation of ethanol to
      acetyl-CoA. This enzyme may also participate in the oxidation of pyruvate to
      acetyl-CoA in certain tissues.

PMID- 16656476
TI  - Leaf water potentials measured with a pressure chamber.
AB  - Leaf water potentials were estimated from the sum of the balancing pressure
      measured with a pressure chamber and the osmotic potential of the xylem sap in
      leafy shoots or leaves. When leaf water potentials in yew, rhododendron, and
      sunflower were compared with those measured with a thermocouple psychrometer
      known to indicate accurate values of leaf water potential, determinations were
      within +/- 2 bars of the psychrometer measurements with sunflower and yew. In
      rhododendron. water potentials measured with the pressure chamber plus xylem sap
      were 2.5 bars less negative to 4 bars more negative than psychrometer
      measurements.The discrepancies in the rhododendron measurements could be
      attributed, at least in part, to the filling of tissues other than xylem with
      xylem sap during measurements with the pressure chamber. It was concluded that,
      although stem characteristics may affect the measurements, pressure chamber
      determinations were sufficiently close to psychrometer measurements that the
      pressure chamber may be used for relative measurements of leaf water potentials,
      especially in sunflower and yew. For accurate determinations of leaf water
      potential, however, pressure chamber measurements must be calibrated with a
      thermocouple psychrometer.

PMID- 16656477
TI  - Auxin Transport in Zea mays Coleoptiles II. Influence of Light on the Transport
      of Indoleacetic Acid-2-C.
AB  - The effect of bilateral irradiation with white light (1000 Meter Candle Sec) on
      the basipetal transport of auxin has been investigated. Illumination of either
      the intact shoot or the excised coleoptile tip of the Zea seedling, decreased the
      amount of diffusible auxin obtained from the tip, and decreased Avena curvature
      response to unilaterally applied indoleacetic acid. Irradiation of the intact Zea
      seedling did not affect the absorption of (14)C-labeled indoleacetic acid from an
      agar block subsequently placed on the decapitated coleoptile. However, light
      caused a significant decrease in the amount of labeled auxin basipetally
      transported, without affecting materially the velocity of that transport. These
      and other observations are interpreted as support for the hypothesis that the
      primary hormonal phenomenon in first-positive phototropism is a light-induced
      impairment in the basipetal transport of auxin.

PMID- 16656478
TI  - Molecular requirements for the biological activity of ethylene.
AB  - The molecular requirements for ethylene action were investigated using the pea
      straight growth test. Biological activity requires an unsaturated bond adjacent
      to a terminal carbon atom, is inversely related to molecular size, and is
      decreased by substitutions which lower the electron density in the unsaturated
      position. Evidence is presented that ethylene binds to a metal containing
      receptor site. CO(2) is a competitive inhibitor of ethylene action, and prevents
      high concentrations of auxin (which stimulate ethylene formation) from retarding
      the elongation of etiolated pea stem sections. It is suggested that CO(2) delays
      fruit ripening by displacing the ripening hormone, ethylene, from its receptor
      site. Binding of ethylene to the receptor site is also impeded when the O(2)
      concentration is lowered, and this may explain why fruit ripening is delayed at
      low O(2) tensions.

PMID- 16656479
TI  - Absorption and translocation of foliar-applied iron.
AB  - The absorption of (59)Fe(3+) by the leaves of various plant species was studied.
      Stomata were found to play a major role in foliar absorption when leaves were
      totally submerged in treatment solutions, and a correlation was found to exist
      between stomatal area and absorption. Day treated leaves absorbed much more than
      did night treated leaves. The use of a surfactant markedly increased absorption.
      Translocation from treated leaves was demonstrated and was found to vary with
      species.

PMID- 16656481
TI  - Effects of light and temperature on the monoterpenes of peppermint.
AB  - Peppermint (Mentha piperita L.) was grown in a growth chamber under several
      combinations of temperature and illumination, and the monoterpenes of each leaf
      pair were analyzed by gas chromatography. Effects on the monoterpenes could be
      seen in the new leaves after a few days in the growth chamber. Long-day
      conditions enhanced growth, with a corresponding increase in the total amount of
      monoterpenes. Either short nights or cool nights, combined with full light
      intensity during the day, enhanced the formation of menthone and depressed the
      accumulation of menthofuran and pulegone. Experiments with interrupted night and
      with low light intensity indicated that photoperiod, as such, does not directly
      influence the terpene composition. It is suggested that the oxidation-reduction
      level of the monoterpenes reflects the oxidation-reduction state of the
      respiratory coenzymes of the terpene-producing cells, and that this, in turn,
      depends on the concentrations of respiratory substrates in the cells. This
      suggestion is based on the likelihood that warm nights cause depletion of
      respiratory substrates, resulting in oxidizing conditions, while cool nights
      preserve high levels of respiratory substrates, and thus maintain reducing
      conditions.

PMID- 16656482
TI  - Inactive and protein precursor pools of amino acids in the soybean hypocotyl.
AB  - There are at least 2 amino pools for leucine and for valine in the soybean
      hypocotyl, a small protein precursor pool and a large inactive pool. The
      precursor pool decreased in size during incubation of excised hypocotyls
      presumably because the cotyledonary sources of amino acids had been removed. The
      precursor pool was subject to expansion by supplying the amino acid externally at
      high concentrations. After the transfer of tissue to unsupplemented media, the
      expanded pool was rapidly depleted.

PMID- 16656483
TI  - Mineral ion contents and cell transmembrane electropotentials of pea and oat
      seedling tissue.
AB  - The relationships of concentration gradients to electropotential gradients
      resulting from passive diffusion processes, after equilibration, are described by
      the Nernst equation. The primary criterion for the hypothesis that any given ion
      is actively transported is to establish that it is not diffusing passively. A
      test was made of how closely the Nernst equation describes the electrochemical
      equilibrium in seedling tissues. Segments of roots and epicotyl internodes of pea
      (Pisum sativum var. Alaska) and of roots and coleoptiles of oat (Avena sativa
      var. Victory) seedlings were immersed and shaken in defined nutrient solutions
      containing eight major nutrients (K(+), Na(+), Ca(2+), Mg(2+), Cl(-), NO(3) (-),
      H(2)PO(4) (-) and SO(4) (2-)) at 1-fold and 10-fold concentrations. The tissue
      content of each ion was assayed at 0, 8, 24, and 48 hours. A near-equilibrium
      condition was approached by roots for most ions; however, the segments of shoot
      tissue generally continued to show a net accumulation of some ions, mainly K(+)
      and NO(3) (-). Only K(+) approached a reasonable fit to the Nernst equation and
      this was true for the 1-fold concentration but not the 10-fold. The data suggest
      that for Na(+), Mg(2+), and Ca(2+) the electrochemical gradient is from the
      external solution to the cell interior; thus passive diffusion should be in an
      inward direction. Consequently, some mechanism must exist in plant tissue either
      to exclude these cations or to extrude them (e.g., by an active efflux pump). For
      each of the anions the electrochemical gradient is from the tissue to the
      solution; thus an active influx pump for anions seems required. Root segments
      approach ionic equilibrium with the solution concentration in which the seedlings
      were grown. Segments of shoot tissue, however, are far removed from such
      equilibration. Thus in the intact seedling the extracellular (wall space) fluid
      must be very different from that of the nutrient solution bathing the segments;
      it would appear that the root is the site of regulation of ion uptake in the
      intact plant although other correlative mechanisms may be involved.

PMID- 16656484
TI  - Gibberellin-auxin interaction in pea stem elongation.
AB  - Joint application of gibberellic acid and indole-3-acetic acid to excised stem
      sections, terminal cuttings, and decapitated plants of a green dwarf pea results
      in a markedly synergistic growth response to these hormones. Synergism in green
      tall pea stem sections is comparatively small, although growth is kinetically
      indistinguishable from similarly treated dwarf sections.Gibberellin-induced
      growth does not appear to be mediated through its effect on auxin synthesis,
      since gibberellin pretreatment of dwarf cuttings fails to elicit an enhanced
      tryptophan-induced growth response of sections, whereas auxin-induced growth is
      strongly enhanced. Also, tryptophan-gibberellin synergism is not significant in
      sections and cuttings of green dwarf peas, while auxin-gibberellin synergism
      is.Administration of gibberellic acid prior to indole-3-acetic acid results in
      greatly increased growth. In reversed order, the application fails to produce any
      synergistic interaction. This indicates that gibberellin action must precede
      auxin action in growth regulation.

PMID- 16656485
TI  - Freezing of xylem sap without cavitation.
AB  - Freezing of stem sections and entire twigs of hemlock (Tsuga canadensis) has been
      demonstrated to occur without increasing the resistance to the movement of water
      through the frozen part after rewarming. This was interpreted to mean that
      freezing did not produce cavitation in the xylem sap even though A) the sap was
      unquestionably frozen; B) it contained dissolved gases; and C) it was under
      tension before freezing and after. Freezing stem sections of some other evergreen
      gymnosperms during the summer again produced no evidence for cavitation of the
      xylem sap. On the other hand, freezing stem sections of some angiosperms
      invariably increased the resistance to sap flow leading to wilting and death in a
      few hours when the sap tension was at normal daytime values at the time of
      freezing. These results were interpreted to mean that the bordered pits on the
      tracheids of gymnosperms function to isolate the freezing sap in each tracheid so
      that the expansion of water upon freezing not only eliminates any existing
      tension but also develops positive pressure in the sap. Dissolved gases frozen
      out of solution may then be redissolved under this positive pressure as melting
      occurs. As the bubbles are reduced in size by this ice pressure developed in an
      isolated tracheid, further pressure is applied by the surface tension of the
      water against air. If the bubbles are redissolved or are reduced to sufficient
      small size by the time the tension returns to the sap as the last ice crystals
      melt, then the internal pressure from surface tension in any existing small
      bubbles may exceed the hydrostatic tension of the melted sap and the bubbles
      cannot expand and will continue to dissolve.

PMID- 16656486
TI  - Ionic balance in different tissues of the tomato plant in relation to nitrate,
      urea, or ammonium nutrition.
AB  - An investigation was carried out to study the cation-anion balance in different
      tissues of tomato plants supplied with nitrate, urea, or ammonium nitrogen in
      water culture.Irrespective of the form of nutrition, a very close balance was
      found in the tissues investigated (leaves, petioles, stems, and roots) between
      total cations (Ca, Mg, K and Na), and total anions (NO(3) (-), H(2)PO(4) (-),
      SO(4) (--), Cl(-)) total non-volatile organic acids, oxalate, and uronic acids.
      In comparison with the tissues of the nitrate fed plants, the corresponding
      ammonium tissues contained lower concentrations of inorganic cations, and organic
      acids and a correspondingly higher proportion of inorganic anions. Tissues from
      the urea plants were intermediate between the other 2 treatments. These results
      were independent of concentration or dilution effects, caused by growth. In all
      tissues approximately equivalent amounts of diffusible cations (Ca(++), Mg(++),
      K(+) and Na(+)), and diffusible anions (No(3) (-), SO(4) (--), H(2)PO(4) (-), Cl(
      )) and non-volatile organic acids were found. An almost 1:1 ratio occurred
      between the levels of bound calcium and magnesium, and oxalate and uronic acids.
      This points to the fact that in the tomato plant the indiffusible anions are
      mainly oxalate and pectate. Approximately equivalent values were found for the
      alkalinity of the ash, and organic anions (total organic acids including oxalate,
      and uronic acids).The influence of nitrate, urea, and ammonium nitrogen nutrition
      on the cation-anion balance and the organic acid content of the plant has been
      considered and the effects of these different nitrogen forms on both the pH of
      the plant and the nutrient medium and its consequences discussed.

PMID- 16656487
TI  - Properties of Higher Plant Mitochondria. I. Isolation and Some Characteristics of
      Tightly-coupled Mitochondria from Dark-grown Mung Bean Hypocotyls.
AB  - The mitochondria isolated from dark-grown mung bean hypocotyls oxidize succinate,
      l-malate, and externally added reduced nicotine adenine dinucleotide (NADH) with
      good respiratory control. While the pattern of respiration resembles that of
      animal mitochondria, there are 4 basic differences between the respiratory
      properties of mung bean and animal mitochondria: A) the ability to oxidize NADH,
      B) the pattern of succinate and malate oxidation, C) the rate of oxygen uptake,
      and D) the adenosine-5'-diphosphate to oxygen ratios.The apparent ;Km' for malate
      of mung bean mitochondria is about one order higher than that expected from malic
      dehydrogenase in animal mitochondria, whereas the affinity for phosphate is about
      5 times higher with plant mitochondria than rat-liver mitochondria. While the
      half-maximal stimulation of respiration by adenosine-5'-diphosphate is
      practically identical to that of animal mitochondria, higher concentrations of
      adenosine-5'-diphosphate cause some decrease in its stimulating action.

PMID- 16656488
TI  - Photosynthesis, Transpiration, Leaf Temperature, and Stomatal Activity of Cotton
      Plants under Varying Water Potentials.
AB  - Cotton plants, Gossypium hirsutum L. were grown in a growth room under incident
      radiation levels of 65, 35, and 17 Langleys per hour to determine the effects of
      vapor pressure deficits (VPD's) of 2, 9, and 17 mm Hg at high soil water
      potential, and the effects of decreasing soil water potential and reirrigation on
      transpiration, leaf temperature, stomatal activity, photosynthesis, and
      respiration at a VPD of 9 mm Hg.Transpiration was positively correlated with
      radiation level, air VPD and soil water potential. Reirrigation following stress
      led to slow recovery, which may be related to root damage occurring during
      stress. Leaf water potential decreased with, but not as fast as, soil water
      potential.Leaf temperature was usually positively correlated with light intensity
      and negatively correlated with transpiration, air VPD, and soil water. At high
      soil water, leaf temperatures ranged from a fraction of 1 to a few degrees above
      ambient, except at medium and low light and a VPD of 19 mm Hg when they were
      slightly below ambient, probably because of increased transpirational cooling.
      During low soil water leaf temperatures as high as 3.4 degrees above ambient were
      recorded. Reirrigation reduced leaf temperature before appreciably increasing
      transpiration. The upper leaf surface tended to be warmer than the lower at the
      beginning of the day and when soil water was adequate; otherwise there was little
      difference or the lower surface was warmer. This pattern seemed to reflect
      transpiration cooling and leaf position effects.Although stomata were more
      numerous in the lower than the upper epidermis, most of the time a greater
      percentage of the upper were open. With sufficient soil water present, stomata
      opened with light and closed with darkness. Fewer stomata opened under low than
      high light intensity and under even moderate, as compared with high soil water.
      It required several days following reirrigation for stomata to regain original
      activity levels.Apparent photosynthesis of cotton leaves occasionally oscillated
      with variable amplitude and frequency. When soil water was adequate,
      photosynthesis was nearly proportional to light intensity, with some indication
      of higher rates at higher VPD's. As soil water decreased, photosynthesis first
      increased and then markedly decreased. Following reirrigation, photosynthesis
      rapidly recovered.Respiration was slowed moderately by decreasing soil water but
      increased before watering. Respiration slowed with increasing leaf age only on
      leaves that were previously under high light intensity.

PMID- 16656489
TI  - Translocation of C in the sugarcane plant during the day and night.
AB  - The time-course of translocation of (14)C from the blades of the sugarcane plant
      was investigated by analysis and radioactive counting of successive samples
      punched from a single blade. In 1 experiment, the time-course was studied by
      determining the specific activity of the carbon dioxide respired by the roots.The
      rate of translocation, expressed as percentage, was highest immediately after the
      application of the radioactive carbon dioxide. Morning-made photosynthate
      translocated a higher percentage during the morning than during the afternoon in
      90-minute periods in the light. Afternoon-made photosynthate translocated as well
      or better than morning-made photosynthate for the first hour in the light.The
      leaf-disk data and the specific activity of the carbon dioxide respired by the
      roots corresponded by showing lower rates of translocation by night than by day
      for several successive days. Also, the translocation of (12)C sucrose was slower
      at night.The (14)C sucrose translocated by day was made primarily by
      photosynthesis; the sucrose translocated by night was made primarily by the
      conversion of other labeled compounds, e.g. organic acids, organic phosphates,
      and insoluble residue.The radioactive constituent of the residue, which was
      converted to sucrose, was tentatively identified as a glucose-xylose-glucuronic
      acid hemicellulose, with most or all of the (14)C in the glucose
      moiety.Translocation of sucrose may be triggered by different mechanisms during
      the night than the day. The conversion of insoluble residue to sucrose by
      increasing the osmotic potential at the source would favor a pressure-flow
      mechanism for nocturnal translocation; whereas translocation by day is thought to
      be a process of phototranslocation, a photoactivation of the translocation
      mechanism.

PMID- 16656490
TI  - Inhibition of Flowering of Xanthium pensylvanicum Wallr. by Prolonged Irradiation
      with Far Red.
AB  - Interrupting each long night with a prolonged period of far red radiant energy
      resulted in the inhibition of floral initiation in cocklebur. Irradiations
      inducing different relative levels of P(FR) from 1 to 2% to 80% had about the
      same effect under 4-hour photoperiods. The lower levels of P(FR) induced by
      continuous far red irradiation were not as effective as the higher levels induced
      by red under 8 and 12-hours photoperiods. The critical P(FR) level required to
      induce inhibition of flowering seems to increase with increasing photoperiods.

PMID- 16656491
TI  - Diffusive resistances at, and transpiration rates from leaves in situ within the
      vegetative canopy of a corn crop.
AB  - At several heights and times of day within a crop of Zea mays, internal leaf
      diffusion resistance (r(i)) and external boundary layer diffusion resistance
      (r(a)) were evaluated by measuring the temperature of a transpiring and a non
      transpiring leaf (simulated by covering both sides of a normal leaf with strips
      of poly-ethylene tape), and by measuring the immediate air temperature, humidity
      and windspeed.Both r(a) and r(i) increased with depth into the crop. However,
      r(a) generally was less than 10% of r(i).Profiles of latent-heat flux density and
      source intensity of transpiration showed that transpiration corresponded roughly
      to foliage distribution (with an upward shift) and were not similar to the
      profile of radiation absorption.The data were compared with heat budget data. The
      2 approaches yielded quite similar height distributions of transpiration per unit
      leaf area and total transpiration resistance.The total crop resistance to
      transpiration was computed as 0.027 min cm(-1). This compares to Monteith's
      values of 0.017 to 0.040 min cm(-1) for beans (Phaseolus vulgaris L.), and
      Linacre's values of 0.015 to 0.020 min cm(-1) for turf.

PMID- 16656492
TI  - Sugar uptake and translocation in the castor bean seedling I. Characteristics of
      transfer in intact and excised seedlings.
AB  - Changes in the dry weights of various parts of the castor bean seedling showed
      that the rates of transfer of material through the cotyledons to the embryonic
      axis exceeded 2 mg/hour after 5 to 6 days of germination. The sugar present in
      the endosperm was predominantly, and in the cotyledon almost exclusively,
      sucrose. Anatomical features were described which contribute to the efficiency of
      the cotyledons as organs of absorption and transmittal of sucrose to the
      embryonic axis, where hexoses are much more prevalent.The ability of the
      cotyledons to absorb sucrose survived removal of the endosperm from the seedling.
      A series of experiments is described in which the cotyledons of such excised
      seedlings were immersed in sucrose-(14)C and measurements made of uptake and of
      translocation to various parts of the seedling. Increasing rates of absorption
      were observed as the sucrose concentration was raised to 0.5 m and these rates
      were maintained for several hours. Removal of the embryonic axis (hypocotyl plus
      roots) drastically altered both the response to sucrose concentration and the
      time course of absorption by the cotyledons.More than 80% of the sugar normally
      entering the cotyledons from the endosperm is transmitted to the embryonic axis
      and this extensive turnover was seen also in pulse/chase experiments with excised
      seedlings. The cotyledons of excised seedlings absorbed sucrose against high
      apparent concentration gradients. The absorption was stimulated by phosphate and
      had a pH optimum at about pH 6.4. It was inhibited by arsenate, azide and 2,4
      dinitrophenol.

PMID- 16656493
TI  - Sugar Uptake and Translocation in the Castor Bean Seedling II. Sugar
      Transformations During Uptake.
AB  - During sucrose uptake by the cotyledons of castor bean seedlings excised from
      their endosperms, small amounts of glucose and fructose accumulate in the medium.
      When these hexoses were supplied separately, it was found that the rate of
      fructose uptake exceeded that of glucose at concentrations up to 0.5 m. Sucrose
      uptake exceeded that of both hexoses combined, particularly at concentrations
      greater than 0.1 m. Only minute amounts of labeled hexoses were recovered from
      the cotyledons after exposure to glucose-U-(14)C or fructose-U-(14)C; sucrose
      contained virtually all of the (14)C in the sugar fraction. The fructose and
      glucose moieties of the extracted sucrose were equally labeled when glucose-U
      (14)C was supplied, and the glucose moiety contained 41% of the (14)C when
      fructose-U-(14)C was the substrate.Several considerations led to the conclusion
      that by far the greater part of sucrose absorbed by the cotyledons was not
      hydrolyzed prior to or during uptake. These included the differential responses
      of hydrolysis and uptake to pH, and to Tris(hydroxymethyl) aminomethane, the
      absence of interference of the hexoses on sucrose absorption and particularly the
      demonstration that when the cotyledons were supplied with fructosyl-(14)C
      sucrose, 90% of the (14)C was retained in the fructose residue of sucrose in the
      cotyledons.

PMID- 16656494
TI  - Responses of a Mutant Strain of Chlamydomonas reinhardi to Prolonged
      Organotrophic Growth.
AB  - The responses of the wild type strain and of the y-2 mutant strain of
      Chlamydomonas reinhardi to long term organotrophic growth were studied. It was
      shown that wild type can be cultured as an organotroph for at least a month with
      little decrease in chlorophyll content and no loss of viability. On the other
      hand, the mutant strain y-2 dies during such organotrophic growth, death
      beginning after 5 to 6 days in the dark. The kinetics of death indicate that the
      loss of 95% of the chlorophyll precedes death and that revertants to wild type
      overgrow such a culture. The results suggest that death of y-2 is correlated with
      the loss of chlorophyll rather than simple metabolic response to organotrophy and
      that the chloroplast or a chloroplast related factor may perform certain
      nonphotosynthetic functions in C. reinhardi. The activities of nicotine adenine
      dinucleotide and nicotine adenine dinucleotide phosphate dependent triose
      phosphate dehydrogenases were studied during long term organotrophic growth of y
      2. It was found that the activities of these enzymes varied in a manner
      consistent with previous findings under these conditions. The activity of
      glutamic dehydrogenase was found to vary as a function of chlorophyll content in
      the mutant strain y-2.

PMID- 16656495
TI  - Phloem water relations and translocation.
AB  - Satisfactory measurements of phloem water potential of trees can be obtained with
      the Richards and Ogata psychrometer and the vapor equilibration techniques,
      although corrections for loss of dry weight and for heating by respiration are
      required for the vapor equilibrium values. The psychrometer technique is the more
      satisfactory of the 2 because it requires less time for equilibration, less
      tissue, and less handling of tissue. Phloem water potential of a yellow-poplar
      tree followed a diurnal pattern quite similar to that of leaves, except that the
      values were higher (less negative) and changed less than in the leaves.The
      psychrometer technique permits a different approach to the study of translocation
      in trees. Measurements of water potential of phloem discs followed by freezing of
      samples and determination of osmotic potential allows estimation of turgor
      pressure in various parts of trees as the difference between osmotic potential
      and total water potential. This technique was used in evaluating gradients in
      water potential, osmotic potential, and turgor pressure in red maple trees. The
      expected gradients in osmotic potential were observed in the phloem, osmotic
      potential of the cell sap increasing (sap becoming more dilute) down the trunk.
      However, values of water potential were such that a gradient in turgor pressure
      apparently did not exist at a time when rate of translocation was expected to be
      high. These results do not support the mass flow theory of translocation favored
      by many workers.

PMID- 16656496
TI  - Studies on Cellulose Synthesis by a Cell-free Oat Coleoptile Enzyme System:
      Inactivation by Airborne Oxidants.
AB  - Particulate cell wall polysaccharide synthetase from oat coleoptiles could use
      either guanosine diphosphate glucose or uridine diphosphate glucose; the latter
      was a much more effective glucose donor. The neutral polymer derived from uridine
      diphosphate glucose utilization yielded, after cellulase digestion, mostly
      cellobiose and to a lesser extent a substance tentatively identified as a mixed
      linkage beta1,4 = beta1,3-trisaccharide; only cellobiose was found after
      guanosine diphosphate glucose utilization. The uridine diphosphate glucose
      utilizing system was inactivated by peroxyacetyl nitrate treatment of intact
      tissue and to a lesser extent by ozone treatment suggesting that this system is a
      possible site of interference with cellulose and non-cellulosic glucan
      biosynthesis in vivo. Direct treatment of the enzyme in vitro by peroxyacetyl
      nitrate, iodoacetamide or p-chloromercuribenzoate also inactivated the enzyme,
      indicating that the mechanism of inactivation possibly involves reaction with
      sulfhydryl groups.

PMID- 16656497
TI  - Matric potentials of leaves.
AB  - A pressure chamber was used to measure matric potentials of frozen and thawed
      leaves. Significant matric potentials were demonstrated in sunflower (Helianthus
      annuus L.), yew (Taxus cuspidata Sieb. and Zucc.), and rhododendron (Rhododendron
      roseum Rehd.). Matric potentials were particularly negative in rhododendron and
      were correlated with the amount of cell wall present and with the volume of water
      outside the leaf protoplasts at comparable matric potentials. It was concluded
      that matric forces in leaves are associated mainly with cell walls, at least
      within the physiological range of water contents. Calculations indicated that the
      water potential of the solution in the cell wall could be estimated for living
      tissue from the sum of matric and osmotic potentials acting on water outside the
      protoplasts.

PMID- 16656498
TI  - Oxygen tension a determining factor in the respiration of potato disks of varying
      thickness.
AB  - The effect of temperature on the respiration rate of potato tuber slices has been
      analyzed in terms of the Arrhenius equation. Freshly cut disks, irrespective of
      thickness, show a linear response to increasing temperature up to 30 degrees with
      an activation energy (E) of approximately 12.0 Kcal. Aged disks less than 1.0 mm
      thick also give a linear response with E similar to that of fresh disks. With
      aged disks above 1.0 mm thick there is a loss of linearity above 20 degrees and E
      falls to about 4.0 Kcal indicating that respiration becomes rate-limited by a
      diffusion process. This departure from linearity can be corrected by raising the
      oxygen tension or by subdivision of thick disks to give thin slices. It is
      concluded that the respiration of aged disks is rate-limited by oxygen deficiency
      and that the inverse relationship between respiration rate and disk thickness is
      in large part attributable to this factor.

PMID- 16656499
TI  - Intracellular localization of nitrate reductase, nitrite reductase, and glutamic
      Acid dehydrogenase in green leaf tissue.
AB  - Greenhouse grown seedlings of corn (Zea mays L.) and foxtail (Setaria faberii
      Herrm.) were used as source material in determining the intracellular
      localization of nitrate reductase, nitrite reductase, and glutamic acid
      dehydrogenase, Nonaqueous and aqueous isolation techniques were used to establish
      that nitrite reductase is localized within the chloroplasts, but that nitrate
      reductase and glutamic acid dehydrogenase are not. Nonaqueous isolation gives
      distribution patterns of nitrite reductase which are the same as those observed
      for NADP-dependent 3-phosphoglyceraldehyde dehydrogenase but which differ
      drastically from the patterns observed for pyruvic acid kinase. The distribution
      patterns for nitrate reductase are the same as those of pyruvic acid kinase. The
      techniques used do not eliminate the possibility that nitrate reductase and
      pyruvic acid kinase are localized on the external chloroplast membrane.The data
      obtained establish that glutamic acid dehydrogenase of green leaves is localized
      within the mitochondria.

PMID- 16656500
TI  - Day-night periodicity of exudation in detopped tobacco.
AB  - Exudate was collected periodically from the root systems of detopped tobacco
      plants. Volume, cations, and (42)K or (86)Rb transfer were measured. According to
      measurements of K by (42)K and by the flame photometer, when concentrations of
      KCl and KNO(3) were lower than 10(-2)m, the K in the exudate came mostly from a
      pool in the plant rather than from the external solution. With higher external
      KNO(3) solutions, within a few hours nearly all of the K in the exudate came
      directly from the external solutions. Studies with (86)Rb lead to the same
      conclusion. In contrast the maximum proportion of K in the exudate that came from
      KCl in the external solution was reached usually in many hours after detopping
      and amounted to from 50 to 75%. The higher the external concentration the faster
      it was reached. These data for KCl are indicative of the (42)K passing through a
      K pool in the root cells. K and Rb from high concentrations of KNO(3) and
      RbNO(3), however, may not pass through such a pool. The addition of 10(-2)m
      KNO(3) into the external solution during exudation essentially eliminated the
      effect of periodicity at least for a period of time and under the conditions of
      the experiments. Hydrochloric acid, mercuric chloride, anaerobiosis, and 2,4
      dinitrophenol had the same effect and each resulted in a massive final exudation
      that usually persisted for 1 to 3 days before stopping. These results all lead to
      a hypothesis that periodicity is regulated at the tonoplast.

PMID- 16656501
TI  - Interactions between hydrostatic pressure and oxygen concentration on the
      germination of lettuce seeds.
AB  - Lettuce seeds were germinated at different hydrostatic pressures and O(2)
      concentrations. Some combinations of pressure and O(2) concentration stimulated
      while others retarded germination. The highest germination rates which occurred
      with pressure application and added O(2) were equalled at atmospheric pressure if
      the O(2) concentration was increased sufficiently. Increasing pressure generally
      retarded germination, but the pressure effect was partly offset by added O(2).
      Sustained pressures affected subsequent germination after pressure was released,
      but only when O(2) was present. Seeds to which pressure was applied in the
      absence of O(2) germinated as well after pressure exposure as untreated seeds.

PMID- 16656502
TI  - Transient effects of light on auxin transport in the Avena coleoptile.
AB  - The transport of indole-3-acetic acid-1-(14)C (IAA) through 4 mm segments of
      etiolated Avena coleoptiles was studied as a function of time by applying IAA in
      apical agar blocks and measuring the basal IAA export rate at 5-minute intervals.
      The transport velocity found in this way is at least 15 mm/hour at 26 degrees .
      Following a 30-minute equilibration period, the export rate is nearly constant
      for at least 50 minutes at physiological donor concentrations. Exposure to about
      3 x 10(5) ergs/cm(2) blue light for 15 minutes leads to a transient reduction in
      the export. The export rate reaches a minimum about 25 minutes after the onset of
      illumination, then rises to reach a maximum by 35 minutes, and subsequently
      declines again. The result is a net export depression during the first 80
      minutes, amounting to some 12 to 17%. Its timing closely matches the timing of
      the light growth response elicited by the same light dosage.At higher IAA
      concentrations (0.5 and 1.8 mg/l), the export rate reaches a peak about 60
      minutes after the initial application of auxin, and thereafter declines rapidly.
      Light increases this decline in export rate, without causing peaks and troughs,
      and even at 0.25 mg/l IAA the transient changes in export appear to be
      superimposed on a gradual decline in export rate after illumination. Blue light
      is effective in all these phenomena; the red far-red system appears to exert no
      effect. The results are discussed in relation to the mechanism of action of light
      both in the light growth response and in phototropism.

PMID- 16656503
TI  - Spectrophotometric Measurements of Phytochrome in vivo and Their Correlation with
      Photomorphogenic Responses of Phaseolus.
AB  - Direct in vivo measurements of phytochrome have been made in Phaseolus vulgaris
      by 2-filter difference spectrophotometry (Ratiospect). All measurements were made
      at 730 versus 800 nm and it is assumed that the Delta (DeltaOD) is directly
      proportional to the PFR concentration of phytochrome present. Dose response
      curves were determined for both physiological and spectrophotometric responses
      for red induction and far-red photoinactivation. For induction, saturation occurs
      at 100 mj/cm(2) and for inactivation at 30 mj/cm(2). The rate of hook opening and
      the physiological response measured 20 hours after induction are both shown to be
      directly proportional to the initial amount of PFR present
      spectrophotometrically. The sensitivity of the tissue correlates well with the
      absolute amount of phytochrome present, the inner portion of the hook having the
      maximum concentration of 0.042 Delta (DeltaOD)/g fresh weight. If the total
      reversible phytochrome concentration is reduced by exposure to red light and
      allowing PFR to decay out of the system the remaining sensitivity of the tissue
      is shown to be directly correlated with the amount of PR remaining in the tissue.
      PFR disappears rapidly in the dark at 25 degrees , and is not detectable after 6
      hours. There is no indication that PFR reverts in the system to PR. At 4 degrees
      , PFR does not disappear measurably up to 1 hour and is nearly totally reversible
      to PR.

PMID- 16656504
TI  - Effect of simazine on nitrate reductase activity in corn.
AB  - The nutritional and environmental parameters required for eliciting increases in
      the nitrogen content and growth of corn (Zea mays L.) by non-toxic levels of
      simazine have been established. Corn seedlings with the endosperm removed 10 days
      after germination, proved to be a suitable test species. The addition of simazine
      to the root-zone area of corn plants grown under both sub-optimal temperatures
      and low nitrate levels, increased the nitrogen content and dry weight of the
      plants by 20 to 25%. This increase was found to be associated with an effect on
      nitrate reductase.

PMID- 16656505
TI  - Ultrastructural and Photometric Evidence for Light-Induced Changes in Chloroplast
      Structure in vivo.
AB  - Photometric evidence for a reversible, red-light induced transmission decrease in
      excised leaf tissue or the thalli of certain marine algae has been obtained under
      conditions which correspond to the occurrence of a light-induced shrinkage of
      chloroplasts within the cells. Evidence supporting this conclusion is: A) The
      kinetics of the nonspecific transmission changes are similar to those observed in
      chloroplasts in vitro. B) The magnitude of the response is larger than could be
      accounted for by any known pigment which absorbs at 546 mmu. C) The light-induced
      transmission changes are optimal at pH 5.5 to 6.5 in the presence of electron
      flow cofactors and weak acid anions, conditions which are optimal for light
      induced chloroplast shrinkage in isolated chloroplasts. D) Examination of
      chloroplast ultrastructure in dark incubated and illuminated chloroplasts reveals
      a flattening of the chloroplast structure and shrinkage.

PMID- 16656506
TI  - Relationship of Cell Sap pH to Organic Acid Change During Ion Uptake.
AB  - Excised roots of barley (Hordeum vulgare, var. Campana) were incubated in KCl,
      K(2)SO(4), CaCl(2), and NaCl solutions at concentrations of 10(-5) to 10(-2)n.
      Changes in substrate solution pH, cell sap pH, and organic acid content of the
      roots were related to differences in cation and anion absorption. The pH of
      expressed sap of roots increased when cations were absorbed in excess of anions
      and decreased when anions were absorbed in excess of cations. The pH of the cell
      sap shifted in response to imbalances in cation and anion uptake in salt
      solutions as dilute as 10(-5)n. Changes in cell sap pH were detectable within 15
      minutes after the roots were placed in 10(-3)n K(2)SO(4). Organic acid changes in
      the roots were proportional to expressed sap pH changes induced by unbalanced ion
      uptake. Changes in organic acid content in response to differential cation and
      anion uptake appear to be associated with the low-salt component of ion uptake.

PMID- 16656507
TI  - High Phytochrome Levels in Cultured Tissue of the Wild Carrot, Daucus carota.

PMID- 16656508
TI  - Interactive Effects of CO(2) and O(2) in Soil on Root and Top Growth of Barley
      and Peas.
AB  - Barley and pea plants were grown under several regimens of different compositions
      of soil atmosphere, the O(2) concentration varying from 0 to 21% and the CO(2)
      concentration from 0 to 8%. In absence of CO(2), the effect of O(2) on root
      length in barley was characterized by equal root lengths within the range of 21
      to 7% O(2) and a steep decline between 7 and 0%. In peas, while showing the same
      general response, the decline occurred between 14 and 7% O(2). Root numbers of
      the seminal roots of barley decreased already with reduction in O(2)
      concentration from 21 to 14%. Dry matter production was affected somewhat
      differently by O(2) and CO(2) concentration. Dry matter production in barley was
      reduced at 14% O(2) while root length decreased between 7 and 0%. In peas, dry
      matter production was favored by low CO(2) concentrations except where there was
      no oxygen. At 21% O(2), increasing CO(2) concentrations did not seem to affect
      root length up to concentrations of 2% CO(2). At 8% CO(2), root length was
      decreased. The inter-active effects of CO(2) and O(2) are characterized by a
      reduced susceptibility to CO(2) at O(2) values below 7%, and a very deleterious
      effect of 8% CO(2) at 7% O(2).

PMID- 16656509
TI  - Sodium absorption by barley roots: role of the dual mechanisms of alkali cation
      transport.
AB  - Radioactively labeled Na(+) absorbed by barley roots was sequestered in an
      intracellular compartment or compartments ("inner" spaces) in which it was only
      very slowly exchangeable with exogenous Na(+). Absorption of this fraction
      proceeded at a constant rate for at least 1 hour.When the rate of Na(+)
      absorption was examined over the range of concentrations, 0.005 to 50 mm, the
      isotherm depicting the relation showed dual kinetics as follows. Over the range,
      0.005 to 0.2 mm, a single Michaelis-Menten term describes the relation between
      the concentration of Na(+) and the rate of its absorption. The mechanism of Na(+)
      absorption operating over this range of concentrations, mechanism 1 of alkali
      cation transport, is severely inhibited in the presence of Ca(2+) and virtually
      rendered inoperative for Na(+) transport by the combined presence of Ca(2+) and
      K(+). The mechanism is equally effective in Na(+) transport whether Cl(-) or F(-)
      is the anion, but is somewhat inhibited when the anion is SO(4) (2-).Over the
      high range of concentrations, 0.5 to 50 mm Na(+), a second, low-affinity
      mechanism of Na(+) absorption comes into play. In the presence of Ca(2+) and
      K(+), this mechanism 2 is the only one to transport Na(+) effectively, since
      Na(+) absorption via mechanism 1 is virtually abolished under these
      conditions.Anaerobic conditions, low temperature, and the uncoupler, 2,4
      dinitrophenol, inhibit Na(+) absorption both at low and high Na(+)
      concentrations.

PMID- 16656510
TI  - Sodium absorption by barley roots: its mediation by mechanism 2 of alkali cation
      transport.
AB  - When barley roots absorb Na(+) at concentrations ranging from 1 to 50 mm, in the
      presence of low concentrations of Ca(2+) and K(+), absorption of Na(+) is
      mediated by carrier mechanism 2 of alkali cation transport, mechanism 1 being
      unavailable for Na(+) transport under these conditions. The absorption isotherm
      depicting the rate of Na(+) absorption as a function of the external Na(+)
      concentration, over the 1 to 50 mm range of concentrations, shows several
      inflections. This stepwise response occurs whether Cl(-) or SO(4) (2-) is the
      counterion, but actual rates of Na(+) absorption are lower in the latter
      case.When the concentration of Na(+) is 50 mm, and the concentration of either
      K(+) or Ca(2+) is increased from nil to 50 mm, the rate of absorption of Na(+) is
      diminished not as a smooth function of increasing concentrations of the
      interfering ions but stepwise. Similarly, when the concentration of K(+) is 50
      mm, and the concentration of either Na(+) or Ca(2+) is increased from nil to 50
      mm, the rate of absorption of K(+) is diminished not as a smooth function of
      increasing concentrations of the interfering ions but stepwise.Together, this
      evidence supports the previous conclusion to the effect that mechanism 2 of
      alkali cation transport possesses a spectrum of carrier sites with different
      ionic affinities.When both K(+) and Na(+) are presented at equivalent
      concentrations over the 1 to 50 mm range, mechanism 2 transports Na(+) almost
      exclusively, and mechanism 1 K(+) almost exclusively. These findings support
      previous conclusions to the effect that the active sites of mechanism 2 have
      higher affinity for Na(+) than for K(+), whereas the reverse is true for
      mechanism 1.

PMID- 16656511
TI  - Phytochrome and Seed Germination. I. Temperature Dependence and Relative P(FR)
      Levels in the Germination of Dark-germinating Tomato Seeds.
AB  - Germination of the dark-germinating seeds of 3 varieties of tomato is controlled
      by the phytochrome system. Germination is inhibited by far red radiation and
      repromoted by red applied after far red. At low temperatures, 17 to 20 degrees ,
      a single, low energy far red irradiation is sufficient to inhibit germination in
      all 3 varieties. At higher temperatures far red is less effective in the
      inhibition of the germination of the tomato seeds. The phytochrome fraction
      present as P(FR) in the dark-germinating seeds of the Ace variety is about 40% of
      the total phytochrome present.

PMID- 16656512
TI  - Effect of Moisture Supply upon Translocation and Storage of C in Sugarcane.
AB  - Low moisture supply, controlled by 3 methods (adding NaCl to a complete nutrient
      solution, allowing a cut stalk to wilt, or withholding irrigation in the field),
      decreased the velocity and percentage rate of translocation of (14)C
      photosynthate. The surplus sucrose not used in growth moved more slowly in the
      phloem and was stored in the stalk.Low moisture supply depressed translocation of
      (14)C-photosynthate more severely than it curtailed formation of (14)C
      photosynthate in the same leaf: therefore, the effect of moisture supply upon
      translocation was primary.Low moisture supply retarded profile development in the
      stem, and a loss in moisture gradient was associated with a steepened slope of
      the profile. These results indicate a flow mechanism of translocation rather than
      diffusion.Results reported now and previously point to the operation of a slow
      pressure-flow mechanism particularly during the night but also during the day;
      superimposed upon this general mass transport is the more rapid process of
      phototranslocation which is independent of sugar gradients and which can cause
      the accumulation of sucrose at the storage-sink.During ripening, storage of
      sucrose in the stalk may be increased by withholding water because less sucrose
      is hydrolyzed in transit, less is used in growth, and the slowly moving sucrose
      has more time for transfer from the phloem to the storage parenchyma.

PMID- 16656513
TI  - Biochemical aspects of parasitism by the angiosperm parasites I. Phosphate
      fractions in the leaves of loranthus and hosts.
AB  - The leaves of Dendrophthoe falcata growing on different trees had differing dry
      solid content. With 1 exception, the parasite leaf contained less dry solid than
      host leaf.A characteristic feature of the loranthus parasite was the accumulation
      of phosphate in excess of that present in host leaves. Expressed as percent of
      the total phosphorus, the parasite tissue contained significantly less acid
      insoluble phosphate than the host leaves. When the acid-insoluble material was
      fractionated into phospholipid, RNA, DNA and phosphoprotein, every component was
      found to be present in a smaller amount in parasite than in host leaf, expressed
      as percent of total phosphate in leaves.A comparative study of the phosphate
      fractions in the infected and uninfected branch of infected host tree revealed
      that, without exception, there was a demonstrable increase in the DNA content of
      the infected branch.

PMID- 16656514
TI  - Gravitational compensation and the phototropic response of oat coleoptiles.
AB  - Avena seedlings were germinated and grown while continuously rotated on the
      horizontal axis of a clinostat. The coleoptiles of these gravity-compensated
      plants were phototropically more responsive than those of plants rotated on a
      vertical axis. When the plants were compensated after unilateral irradiation,
      phototropic curvature of the shoot progressed for the next 6 hours, with the rate
      of curving decreasing about 3 hours after irradiation. The decrease in rate was
      less in the plants gravity-compensated before irradiation than in those
      vertically rotated. In the period 70 to 76 hours after planting, the growth rate
      of the compensated coleoptiles was significantly less than that of the vertically
      rotated seedlings. The greater phototropic curvature, the decreased growth rate,
      and the slower rate of straightening of the curved, compensated shoot can be
      correlated with several consequences of compensation: an increase in sensitivity
      to auxin, a lowering of auxin content in the coleoptile tip, and possibly, from
      an interaction between compensation and phototropic stimulation, an enhanced
      difference in auxin transport between the illuminated and shaded halves of the
      unilaterally irradiated shoot.The phototropic response of the vertically rotated
      seedling was significantly different from that of the vertical stationary,
      indicating the importance of vertically rotated controls in clinostat
      experiments.

PMID- 16656515
TI  - Water and salt stresses, kinetin and protein synthesis in tobacco leaves.
AB  - The capacity of tobacco (Nicotiana rustica) leaf discs to incorporate l-leucine
      (14)C into proteins was measured. Leaf discs were obtained from plants which
      experienced soil water depletion, or which were exposed to a saline or osmotic
      stress in the root medium. The stresses were brief of relatively short duration
      and water potential did not decrease below 4 bars in the root media. Leaf discs
      were sampled 2 hours after stress removal, achieved by reirrigation, or
      replacement of saline and osmotic solutions with normal nutrient solution. Plants
      were always turgid when leaves were sampled.All stressed tissues showed reduced
      capacity to incorporate l-leucine (14)C into protein. The reduction was about 50%
      and could not be attributed either to reduced uptake into the discs, or to
      possible isotopic dilution. Incorporation decreased progressively with leaf age
      in control discs as well as in stressed leaf discs. At all ages tested,
      incorporation in stressed discs was lower than that of the control. Full recovery
      of incorporation capacity in stressed discs was obtained when discs were sampled
      72 hours after stress removal but not earlier.Kinetin pretreatment prior to
      incubation with labelled leucine partially restored incorporation in stressed
      discs. The differences in response to kinetin of stressed and control discs
      suggest a lower endogenous level of cytokinins in the stressed discs. The results
      were qualitatively similar regardless of the kind of stress given to the plants
      during pretreatment. This supports the hypothesis that the normal supply of root
      cytokinins is important in shoot metabolism.

PMID- 16656516
TI  - Incorporation of P and C into Photosynthetic Products of Ankistrodesmus braunii
      as Affected by X-Rays.
AB  - The incorporation of (32)P and (14)C into organic compounds by Ankistrodesmus is
      strongly inhibited by X-rays. In the same phosphorylated compounds (32)P
      incorporation apparently is more severely inhibited by X-rays than the (14)C
      labelling. The (32)P-incorporation into organic compounds is more strongly
      inhibited than (32)P-labelling of inorganic phosphate in the cell. The inhibition
      of (32)P-incorporation into a number of compounds is strikingly uniform. It is
      concluded that the inhibition of (32)P-incorporation and of (14)C-incorporation
      into phosphorylated compounds in vivo is due to an uncoupling by X-rays of
      photophosphorylation as in vitro. The difference in X-ray sensitivity of (14)C-
      and (32)P-incorporation into one organic phosphorous compound is attributed to a
      dual action of X-rays on (32)P-incorporation in organic compounds (both via the
      uncoupling of photophosphorylation) and only a single effect on (14)C
      incorporation and (32)P-labelling of inorganic phosphate. The effect of X-rays on
      (14)C-incorporation into organic compounds included inhibition in most cases but
      also stimulation as in the case of glycolic acid. These differences may be due to
      interference in the intercellular regulations following the application of X
      rays. The inhibition of (14)C-incorporation in many cases exhibits different
      behaviour at low (<200 krad) and high doses. These changes are discussed on the
      assumption that at the lower doses X-rays cause uncoupling of
      photophosphorylation and at the higher doses an additional inhibition of electron
      transport.

PMID- 16656517
TI  - Gibberellic Acid-enhanced synthesis and release of alpha-amylase and ribonuclease
      by isolated barley and aleurone layers.
AB  - Gibberellic acid enhances the synthesis of alpha-amylase in isolated aleurone
      layers of barley-seeds (Hordeum vulgare var. Himalaya). In the presence of 20 mm
      calcium chloride the amount of enzyme obtained from isolated aleurone layers is
      quantitatively comparable to that of the half-seeds used in earlier studies.
      After a lag period of 6 to 8 hours enzyme is produced at a linear rate.
      Gibberellic acid does not merely trigger alpha-amylase synthesis, but it is
      continuously required during the period of enzyme formation. Enzyme synthesis is
      inhibited by inhibitors of protein and RNA synthesis. Small amounts of
      actinomycin D differentially inhibit enzyme release and enzyme synthesis
      suggesting 2 distinct processes. Gibberellic acid similarly enhances the
      formation of ribonuclease which increases linearly over a 48 hour period. During
      the first 24 hours the enzyme is retained by the aleurone cells and this is
      followed by a rapid release of ribonuclease during the next 24 hour period. The
      capacity to release the enzyme is generated between 20 and 28 hours after the
      addition of the hormone. Ribonuclease formation is inhibited by inhibitors of
      protein and RNA synthesis. These inhibitors also prevent the formation of the
      release mechanism if added at the appropriate moment.

PMID- 16656518
TI  - Tissue Respiration and Mitochondrial Oxidative Phosphorylation of NaCl-Treated
      Pea Seedlings.
AB  - The effect of sodium chloride added to root medium of pea seedlings on
      respiratory activity of tissue segments and on isolated mitochondria was studied.
      Salinization enhances the respiration of leaves about one-third on a fresh
      weight, dry weight or protein basis. Roots and stems show only 10 to 15%
      respiratory stimulation. The onset of respiratory increase in leaves roughly
      parallels the increase in NaCl content and the decrease in growth rate. At a
      later stage the elevated respiration is apparent in treated plants even though
      the concentration of NaCl reaches a plateau and osmotic adjustment is being
      reached. Stimulation of respiration was found in both etiolated and green plants.
      Experiments with DNP show that simple uncoupling by salt is not involved; the
      respiratory increase in control and treated tissue is proportionally the same.In
      accordance with increased respiration rates observed in vivo, mitochondria from
      salt-treated plants show higher rates of oxygen uptake on several substrates. The
      effect of NaCl added during growth is long term and is distinct from the effect
      of NaCl added to mitochondria isolated from control plants. Since P/O ratios are
      not affected by NaCl, the potential for oxidative phosphorylation in salt
      affected tissue appears to increase. It is postulated that this increase may lead
      to changes in ADP and ATP content, and in turn, affect regulation of metabolic
      pathways.

PMID- 16656519
TI  - An explanation of the inhibition of root growth caused by indole-3-acetic Acid.
AB  - Low concentrations of indole-3-acetic acid inhibit the growth of pea root
      sections by inducing the formation of the growth regulator, ethylene gas.
      Ethylene is produced within 15 to 30 minutes after indole-3-acetic acid is
      applied and roots begin to swell immediately after they are exposed to the gas.
      Carbon dioxide competitively inhibits ethylene action in roots, impedes their
      geotropic response, and partially reinstates auxin inhibited growth. It is
      concluded that ethylene participates in the geotropic response of roots, but not
      that of stems.

PMID- 16656520
TI  - Action and interaction of red and far-red radiation on lipoxidase metabolism of
      squash seedlings.
AB  - Lipoxidase, in the cotyledons of squash (Cucurbita moscata) seedlings grown in
      the dark, reached its peak activity on the fifth day and then declined to its
      lowest activity on the eighth day. Under continuous irradiation, the rate of
      enzyme disappearance was accelerated by red (655 mmu) and was retarded by far-red
      (735 mmu) radiation. Acceleration of enzyme disappearance caused by red light was
      reversed repeatedly by far-red light in seedlings that received an initial
      exposure to red radiation. These responses were independent of the duration of
      irradiation at each of the alternating wavebands. No change was observed when the
      white light was administered either 24 hours before or 24 hours after the red,
      far-red treatment.The lipoxidase system of the seedlings given an initial
      exposure to far-red radiation also responded reversibly to alternating far-red,
      red extended exposures, but it failed to respond reversibly when short exposures
      were employed. Similarly, no change occurred in these seedlings when either pre-
      or post-treatment with the white light was applied.These results demonstrate that
      the capacity of lipoxidase to act reversibly depends primarily on the duration of
      exposure and on the kind of light (red or far-red) to which the seedlings were
      exposed initially. In spite of these variations, lipoxidase metabolism can be
      considered an additional biochemical manifestation of red, far-red reaction that
      operates in the photomorphogenesis of plants.

PMID- 16656521
TI  - Inhibitory oxidation products of indole-3-acetic Acid: 3-hydroxymethyloxindole
      and 3-methyleneoxindole as plant metabolites.
AB  - Extracts of pea seedlings (Pisum sativum, variety Alaska) oxidize indole-3-acetic
      acid to a bacteriostatic compound which has been identified as 3
      hydroxymethyloxindole. At physiological pH this compound is readily dehydrated to
      3-methyleneoxindole, another bacteriostatic agent. The extracts of pea seedlings
      also contain a reduced triphosphopyridine nucleotide-linked enzyme which reduces
      3-methyleneoxindole to 3-methyloxindole, a non-toxic compound.These enzymatic
      reactions also take place in intact seedlings; thus, a pathway of indole-3-acetic
      acid degradation via oxindoles appears to be pertinent to plant metabolism.The
      significance of such metabolism lies in the fact that a key intermediate of this
      pathway, 3-methyleneoxindole, is a sulfhydryl reagent capable of profound effects
      on metabolism and growth.

PMID- 16656522
TI  - Periods of sensitivity to chilling in germinating cotton.
AB  - Cotton seedlings were subjected to a 96 hour chilling treatment (5 degrees or 10
      degrees ) after periods of germination at 31 degrees ranging from 0 to 48 hours.
      Inhibition of subsequent growth at a favorable temperature by chilling was
      dependent on level of low temperature and stage of seedling development when
      chilled. Two periods of chilling hypersensitivity were observed during
      germination: 1) coincident with subjection of seed to a germination environment;
      and 2) after 18 to 30 hours of germination at 31 degrees . Subsequent growth of
      seedlings chilled after 12 to 18 hours or 48 hours of germination at 31 degrees
      was relatively unaffected. It is suggested that chilling alters specifically
      timed events that occur at the initiation of germination and after 18 to 30 hours
      of germination, and that alteration of these germination processes is visited on
      long term subsequent growth of the plant.

PMID- 16656523
TI  - Correlative Studies on Plant Growth and Metabolism II. Effect of Light and of
      Gibberellic Acid on the Changes in Protein and Soluble Nitrogen in Lettuce
      Seedlings.
AB  - Protein and soluble nitrogen distribution in different parts of lettuce seedling
      was studied in light and darkness and in presence and absence of gibberellic
      acid. In dark, applied gibberellic acid failed to show any marked effect on the
      nitrogen changes in lettuce. Light inhibits translocation of nitrogen reserves
      from the cotyledons. Gibberellic acid reverses the light inhibition of
      longitudinal growth but has no effect on the inhibition of translocation from the
      cotyledons. Light grown, gibberellic acid treated seedlings exhibit a pattern of
      protein and soluble-N which is characteristic of the dark grown seedlings. Thus
      gibberellic acid not only causes morphological reversal of light inhibition but
      also shifts the nitrogen metabolism of light grown plants, close to that of
      plants grown in darkness.

PMID- 16656524
TI  - Physiological Effects of Gibberellic Acid. IX. Recovery of Gibberellic Acid
      Following Incubation with Endosperm.
AB  - To determine the fate of gibberellic acid (GA(3)), solutions were incubated for
      24 hours with or without barley endosperm and were subsequently applied to dwarf
      maize seedlings. Hormone activity appeared to increase as a result of incubation
      with endosperm. This apparent increase in GA(3) concentration was probably due to
      a synergistic interaction between GA(3) and endosperm constituents, particularly
      carbohydrate, released during the incubation period. It is concluded that
      relatively little hormone is inactivated during the initiation of endosperm
      mobilization.

PMID- 16656525
TI  - Biosynthesis of phenolic compounds in first internodes of sorghum: lignin and
      related products.
AB  - Lignin biosynthesis in excised tissues of Sorghum vulgare variety Wheatland milo
      incubated in air with and without prior infiltration with H(2)O was presumably
      limited by H(2)O(2) production and was dependent upon an endogenous substrate,
      probably starch. In solution culture without shaking, this conversion of
      endogenous material was partially blocked at some step prior to p-hydroxycinnamic
      acid. The synthesis was light independent and continued protein synthesis was not
      required. The accumulation of lignin products was paralleled by an increase in
      dhurrin, alkaline sensitive esters of p-hydroxycinnamic, ferulic and sinapic
      acids, and flavin coenzymes, especially flavin-adenine dinucleotide. There was no
      detectable evidence of competition for substrates with other phenols such as
      anthocyanins or with the growth of adventitious roots. There was evidence,
      however, of mechanisms limiting lignification in the first internode in the
      intact seedling. Comparisons are made with lignin production in comparable
      tissues of Phleum.

PMID- 16656526
TI  - Development of soluble and insoluble invertase activity in washed storage tissue
      slices.

PMID- 16656527
TI  - Degradation of 2,4,5-trichlorophenoxyacetic Acid in woody plants.
AB  - Woody plants were sprayed with an aqueous homogenate of the n-butyl ester of
      2,4,5-trichlorophenoxyacetic acid. Leaf extracts were studied by gas-liquid
      chromatography, and 2,4,5-trichlorophenol was always present. The formation of
      2,4,5-trichloroanisole apparently did not occur.

PMID- 16656529
TI  - Metabolic Changes in After-Ripening Seed of Prunus cerasus.
AB  - Metabolic changes were studied in embryonic axes and cotyledons isolated from
      after-ripening seeds of Prunus cerasus. During the seventh week of after
      ripening, a striking increase in the respiration rate at 25 degrees of embryonic
      axes occurred along with a sharp change from the dormant to non-dormant state of
      the seed. On the basis of C-6/C-1 ratio determinations this change may be related
      to an increased activity of the pentose phosphate cycle.

PMID- 16656530
TI  - Reversal of hydroxyproline-induced inhibition of elongation of Avena coleoptiles.
AB  - Hydroxy-l-proline-induced inhibition of elongation of Avena coleoptile segments
      was measured in water and in indole-3-acetic acid. This inhibition was completely
      reversed by l-proline.Time-sequence experiments revealed that some time had to
      elapse, or some elongation had to occur, prior to the onset of hydroxyproline
      inhibition. The presence of sucrose supported the rate of auxin-induced
      elongation throughout a 24-hour period, and enhanced the effectiveness of
      hydroxyproline as an inhibitor of elongation.The application of adenosine
      triphosphate effectively counteracted the hydroxy-proline-induced inhibition of
      elongation; completely in water, and partially in indole-3-acetic acid. Optimal
      ATP concentrations were between 0.25 and 0.75 mm. Similarly, guanine-HCL, l
      glutamic acid, and l-ornithine-HCL were capable of reversing the hydroxyproline
      inhibition. Other compounds that were tested but which proved to be less
      effective are tabulated.It is suggested that hydroxyproline may exert its
      inhibitory effect on the protein and/or RNA synthesis necessary for elongation of
      the oat coleoptile by interference with the metabolism of adenosine triphosphate
      or other high energy compounds.

PMID- 16656531
TI  - Flowering Responses of Xanthium pensylvanicum to Long Dark Periods.
AB  - The flowering of Xanthium pensylvanicum Wallr. was investigated using long dark
      periods. Attempts were made to ascertain evidence for the involvement of a
      flowering rhythm in Xanthium by use of variable-dark-length and light
      interruption experiments.It was found that factors such as plant height (age),
      partial defoliation, and various pretreatments had little effect on the general
      nature of the flowering response. Maximum sensitivity to red light occurred at
      the eighth hour of 24-, 48-, and 72-hour dark periods. Temperature had little
      influence on this timing. The time of maximum sensitivity was delayed to the
      tenth hour by a pretreatment with 8 hours of darkness followed by 6 hours of
      light. These properties are similar to those of Pharbitis, which showed a clear
      rhythmic sensitivity to red light interruptions. The possible involvement of a
      rapidly damping rhythm of sensitivity to red light is discussed on the basis of
      this similarity. A distinct flowering rhythm similar to that of soybean and
      Chenopodium was not found. Although the results are inconclusive with respect to
      a rhythm, they do indicate similarities and differences to the responses of other
      short-day plants in which rhythms have been demonstrated.

PMID- 16656532
TI  - Isolation and identification of indole-3-ethanol (tryptophol) from cucumber
      seedlings.
AB  - Crude ether extracts of green shoots of Cucumis sativus L. promoted the
      elongation of cucumber hypocotyl segments. Purification of the extract was
      accomplished by DEAE cellulose, silicic acid, and magnesium silicate
      chromatography followed by gel filtration and preparative thin layer
      chromatography. Identification of the growth promoter as indole-3-ethanol was
      achieved by mass spectrometry, thin layer and gas chromatography, and ultraviolet
      and visible spectroscopy, as well as by physiological characteristics.

PMID- 16656533
TI  - Kinetics of the Daily Rate of Photosynthesis at Low Temperatures for two
      Conifers.
AB  - The daily course of photosynthesis at low temperatures in 2 coniferous species,
      Pinus ponderosa Laws., and Pseudotsuga menziesii (Mirb.) Franco, were studied
      using controlled environment facilities. After having been grown at a 23 degrees
      day, and 19 degrees night for a year, seedlings were acclimatized for 4 months to
      either a 3 degrees , 7 degrees or 11 degrees day all under 1200 ft-c of light and
      followed by a 16-hour night at 3 degrees . Measurement of photosynthesis at 1200
      ft-c revealed 3 separate responses. First, the rapidity at which the plants
      attained their maximum photosynthesis when the lights were turned on depended
      upon the species, the current temperature, and the previous temperature condition
      to which the plants had become acclimatized. The warmer the day temperature the
      sooner the daily maximum was reached. Second, fluctuations in the rate of
      photosynthesis during the day varied with the species and the day temperature.
      Photosynthesis in both fir and pine kept at an 11 degrees day and pines kept at a
      7 degrees day attained a daily peak rate followed by a decline. This decline
      occurred even though temperature and light were kept constant, the CO(2) level
      was returned to 320 ppm from 290 ppm, and the plants were kept well watered. At a
      3 degrees day neither species showed this decline. Third, a plant transferred to
      another temperature acquired a new stable daily photosynthetic pattern. The
      number of days required for stabilization depended upon the previous temperature
      history of the plant. The adjustment rate was faster when the temperature was
      raised than when it was lowered.

PMID- 16656534
TI  - Control of Flowering of Xanthium pensylvanicum by Red and Far-red Light.
AB  - A study was made of the effects of various durations, intensities and
      combinations of red and far-red light interruptions on the flowering responses of
      Xanthium pensylvanicum Wallr. A dual response to treatments of far-red light was
      observed. In short dark periods, far-red light alone did not greatly affect
      flowering but was able to overcome the inhibition of flowering caused by red
      light. In dark periods longer than 15 hours, far-red inhibited flowering and
      added to rather than overcame the inhibition by red light. The dark period length
      required for far-red inhibition remained the same whether far-red was given at
      the start or at the eighth hour of darkness.In 48-hour dark periods Xanthium
      showed 3 responses to additions of red and far-red light breaks: A) response to
      red light; B) response to far-red light; and C) response to red followed by far
      red light. Red light given any time in the first 30 hours of darkness overcame
      the inhibitory effect of far-red light given at either the start or the eighth
      hour of darkness. Red light given later than the thirtieth hour did not overcome
      the far-red effect.Approximately the same energy of red light was required to
      overcome the inhibitory effect of far-red at the second hour of darkness as was
      required to produce maximum red light inhibition at the eighth hour. Although far
      red light was most inhibitory when given early in a long dark period,
      approximately the same energy of far-red light was required to saturate the far
      red response at the fourth, eighth and sixteenth hours.The results are discussed
      in relation to other reports of far-red inhibition of flowering in short-day
      plants.

PMID- 16656535
TI  - Isolation, Purification, and Characterization of an Endogenous Root-promoting
      Factor Obtained from Basal Sections of Pear Hardwood Cuttings.
AB  - Basal segments taken from Old Home and Bartlett pear hardwood cuttings collected
      at intervals during the rooting period in September were extracted with ethanol
      and fractionated by paper chromatography in different solvent systems. Different
      zones on the chromatograms were bioassayed by the mung bean rooting test, which
      showed high levels of promotion in Old Home basal extracts when the cuttings were
      obtained during the period of maximum rooting. Extracts from Bartlett cuttings,
      however, showed considerably less promotion activity in the bioassay but did show
      high levels of inhibitory activity.After the easily-rooted Old Home cuttings had
      been in the rooting medium for 10 days, a highly active endogenous root-promoting
      material was found in extracts from basal segments of cuttings having buds and
      which had been treated with indolebutyric acid. Similar extracts obtained from
      disbudded cuttings, or from cuttings with buds but not treated with indolebutyric
      acid, lacked this rooting-factor. Extracts obtained from all types of the
      difficult-to-root Bartlett cuttings also lacked this rooting-factor. The latter
      is believed to be produced by physiologically active Old Home buds, and is very
      effective in the mung bean bioassay, even at extremely low concentrations.From
      paper chromatographic studies, tests with spray reagents, solubility
      determinations, biological tests, UV spectrum analysis, and infrared
      spectroscopy, it is believed that this rooting factor could be a condensation
      product between exogenous auxin (indolebutyric acid) and a phenolic compound
      produced by physiologically active Old Home pear buds.

PMID- 16656536
TI  - Transpiration as a function of soil temperature and soil water stress.
AB  - An apparatus was developed for the measurement of transpiration rates of
      Trifolium repens. The transpiration rates were measured under controlled
      conditions of soil water stress and soil temperature. Other environmental
      parameters such as air temperature, relative humidity, light intensity and air
      speed were held constant. Diffusive resistances were calculated and stomatal
      aperture changes were recorded for all treatment combinations. A significant
      interaction between soil water stress and soil temperature was observed for
      stomatal closures. Stomatal closure was observed even in the so-called wet range
      of soil water stress. An increase in mesophyll resistance or incipient drying was
      observed for several treatment combinations. The mesophyll resistance was shown
      to increase as soil water stress increased.

PMID- 16656537
TI  - Assay of substances stimulatory to legume nodule formation.
AB  - Two methods were developed for the assay of substances stimulatory to the
      nodulation of bean (Phaseolus vulgaris) roots growing from segments of hypocotyl
      tissue. Coconut water was the chief source of active material, but extracts of
      cotyledons, hypocotyls and leaves of beans and of horse chestnut fruits were also
      stimulatory. High concentrations of nitrate improved nodulation both in the
      presence and absence of coconut water. The ash of coconut water was inactive.
      Whole alfalfa seedlings formed nodules in the dark when grown in the split
      medium, but nodulation was not improved by the addition of coconut water.

PMID- 16656538
TI  - Partial purification of a legume nodulation factor present in coconut water.
AB  - The nodulation of adventitious roots growing from segments of bean hypocotyl
      tissue was used as a bioassay for the material present in coconut water which
      stimulated nodulation. The active material in coconut water is acidic, but it was
      not possible to extract it from an acid solution with organic solvents. A
      purification of approximately 70-fold (on a dry wt basis) was obtained using
      activated charcoal, but at least 10 different compounds were present in the
      active fractions. A purified fraction of coconut water, which is stimulatory to
      the growth of carrot root explants, was active in the nodulation assay at a
      concentration of 2 mug/ml. This represents a 4000-fold purification of the
      diffusible fraction of coconut water. The charcoal fractionation procedure can be
      applied to the active material present in extracts of bean leaves.

PMID- 16656539
TI  - Formation of amylase in disks of bean hypocotyl.
AB  - Amylase activity has been studied in disks of hypocotyl of Phaseolus vulgaris L.
      Although some activity is present in untreated hypocotyls, it is greatly
      increased when disks are incubated 4 days in water containing kinetin (5
      mg/liter). Gibberellic acid and 2,4-dichlorophenoxyacetic acid do not increase
      this activity appreciably. The increased activity can be shown by subsequently
      incubating the disks on starch agar plates and testing these with iodine
      potassium iodide solution, or by using the original incubation medium and
      extracts of the disks in reactions with soluble starch. A variety of tests favor
      the assumption that the enzyme is alpha-amylase and that it is synthesized during
      the incubation period.

PMID- 16656540
TI  - Inhibition of photo-induced electron transport and related reactions in isolated
      chloroplasts by phenol.
AB  - Phenol inhibits the Hill reaction with several Hill oxidants and the accompanying
      non-cyclic phosphorylation. It inhibits also pseudocyclic and cyclic
      phosphorylation. Partial reactions which are dependent on cyclic electron flow
      are inhibited too, but electron flow from ascorbate via dichlorophenolindophenol
      to TPN is not. The activity of various benzene and phenol derivatives was
      compared. It is concluded that the inhibition is a result of interfering with an
      electron carrier which participates in cyclic and non-cyclic electron flow.

PMID- 16656541
TI  - Distribution of an Indoleacetic Acid-oxidase-inhibitor in the Storage Root of
      Daucus carota.
AB  - Indoleacetic acid (IAA)-oxidase from both secondary phloem and xylem was
      dependent on 2,4-dichlorophenol for activity, and was enhanced by addition of
      Mn(2+). The pH optimum was 6.0 from both tissues. IAA-oxidase and its inhibitors
      were distributed differently in the secondary phloem and secondary xylem of
      carrot root. In the phloem a high IAA-oxidase activity was distributed uniformly
      along the radius but in the xylem a somewhat lower concentration decreased from
      the cambium. IAA-oxidase inhibitor in the phloem increased exponentially from a
      very low concentration near the cambium, whereas in the xylem an appreciable
      concentration was present near the cambium, decreasing linearly with distance
      from the cambium. Longitudinal gradients in the xylem parallel studies by other
      workers with the greatest IAA-destroying capacity present in older tissues. In
      the xylem inhibitor decreased and IAA-oxidase increased from the root apex. In
      the phloem IAA-oxidase was uniform, whereas the inhibitor increased in older
      tissue.The IAA-oxidase inhibitors in phloem and xylem may be different. In the
      xylem the IAA-oxidase inhibitor may be a lignin precursor present in young cells
      which disappears as lignification proceeds. In the phloem IAA-oxidase reacting
      with endogenous IAA appears to form a physiologically active product.

PMID- 16656542
TI  - Isolation and characterization of peanut spherosomes.
AB  - Spherosomes of cotyledons of germinating peanuts (Arachis hypogea L.) were
      examined by electron microscopy and found to be particles about 1.0 to 2.0 mu in
      diameter bounded by a limiting membrane. Isolated spherosomes appear similar to
      spherosomes in situ. The isolated spherosomes are composed of 98.1% total lipids,
      0.77% phospholipid and 1.27% protein by dry weight. The amounts of protein and
      phospholipid associated with the isolated spherosomes are sufficient to account
      for limiting membranes. Spherosomes amply account for the lipid in a peanut
      cotyledon. The activity of lipase and fatty acyl-Coenzyme A synthetase is not
      associated with the isolated spherosomes. This suggests that peanut spherosomes
      are principal sites of lipid storage but not of lipid degradation.

PMID- 16656543
TI  - Inhibition of Flowering in Xanthium pensylvanicum Walln. by Ethylene.

PMID- 16656544
TI  - Translocation of radioactive kinetin.
AB  - Kinetin has generally been thought to be immobile in plants. This was confirmed
      in the case of laminar applications in this study, but not in regard to petiole,
      vein, or root applications. Radioactivity from kinetin-8-(14)C (Kn(*)) moved
      freely in the vascular system of several types of leaves. This movement was
      usually distal to the point of application and seemed to occur with the
      transpiration stream. Basipetal as well as acropetal translocation of radioactive
      kinetin was achieved in tobacco leaves. The translocated material was extracted
      from veinal tissue, shown to be radioactive, and to be able to retard senescence.
      Similar but less decisive results were obtained from agar blocks inserted into
      the vascular system of leaves receiving Kn(*) by petiole uptake.A bioassay
      employing disks from primary bean leaves was developed for the qualitative
      determination of substances like kinetin which possess the ability to retard
      chlorophyll breakdown and plant senescence. The use of radioactive kinetin
      provided a refinement in this bioassay because treated non-senescent areas could
      be correlated with exposed areas on radioautographs made from dried leaf
      disks.Root treatments showed that cotton seedlings did not take up Kn(*) but that
      similarly treated tobacco seedlings both absorbed and translocated the isotope
      readily.

PMID- 16656545
TI  - Correlative Studies on Plant Growth and Metabolism. III. Metabolic Changes
      Accompanying Inhibition of the Longitudinal Growth of Stem and Root by Kinetin.
AB  - Kinetin-induced expansion of lettuce (Lactuca sativa) cotyledons and inhibition
      of root are accompanied by parallel changes in protein nitrogen. However, during
      its inhibition of the longitudinal growth and water uptake of hypocotyl and pea
      (Pisum sativum) epicotyl sections kinetin markedly stimulates protein synthesis.
      Kinetin seems to separate auxin induced effects on protein synthesis and water
      uptake and indicates that water uptake and protein synthesis may not necessarily
      be correlated.In contrast to gibberellic acid, kinetin restricts in lettuce
      seedlings, the mobilization of nitrogen reserves from the cotyledons, and kinetin
      induced growth is accompanied by a high protein nitrogen/soluble-nitrogen ratio
      which is characteristic of growth in light. Growth in light may be under the
      dominant control of kinins.

PMID- 16656546
TI  - Formation of a soluble amylopectin-like polysaccharide in potato tubers.
AB  - When potato sprouts or potato tuber slices were incubated with 0.1 m glucose 1
      phosphate, a soluble amylopectin-like polysaccharide was excreted to the medium.
      This polysaccharide was found to be a very good primer for phosphorylase and a
      poor one for starch synthetase. Beside the formation of this extracellular
      polysaccharide, a more branched intracellular polysaccharide could be isolated.
      This polysaccharide was an excellent primer for starch synthetase. Fructose 6
      phosphate, glucose 6-phosphate, fructose 1,6-diphosphate, glucose or sucrose
      could not substitute for glucose 1-phosphate. 2,4-Dinitrophenol or nitrogen did
      not affect the excretion of the polysaccharide. Some properties of these 2
      polysaccharides are described.

PMID- 16656547
TI  - Relative importance of reradiation, convection, and transpiration in heat
      transfer from plants.
AB  - For a plant of average spectral properties and average diffusion resistance (2
      sec/cm), diurnal variations in the energy dissipated by reradiation, convection,
      and transpiration have been explicitly calculated and plotted for certain
      environmental conditions as measured at St. Paul, Minnesota. These conditions
      represent the environments of characteristic types of days and of characteristic
      types of leaves. In all situations reradiation is overwhelmingly the dominant
      mode of heat transfer.A new method for the calculation of Bowen's ratio is also
      presented which gives results in very good agreement with older procedures. For
      certain individual leaves the energy dissipated by convection is found to be
      greater than that dissipated by transpiration. For a crop as a whole, however,
      transpiration is found to be by far the most important.

PMID- 16656548
TI  - Relative permeabilities of plastic films to water and carbon dioxide.
AB  - The permeabilities of several types of plastic films to water and to carbon
      dioxide were measured. No material was found to have a carbon dioxide
      permeability as great as its water permeability.

PMID- 16656549
TI  - Relation Between Calcium and Strontium Transport Rates as Determined
      Simultaneously in the Primary Root of Zea mays.
AB  - Root segments of Zea mays 55 mm long, were exposed to nutrient containing (85)Sr
      and (45)Ca tracers. Translocation rather than uptake was measured, using a newly
      designed glass compartmentation system and validated tracer analytic model. Ca
      transport from solutions containing between 0.25 and 5.0 mm Ca was only slightly
      affected by concentration, but translocation from 0.25 to 0.05 mm solutions was
      markedly reduced. Maximum transport of strontium from nutrient containing 0.05 mm
      Ca was twice that from 2.5 mm Ca, and also twice the maximum calcium transported.
      Thus, under the condition simulating calcium depletion, i.e., 0.05 mm Ca, greater
      amounts of strontium were transported. In these cases the solutions also
      contained stable strontium at concentrations between 0.25 and 5.0 mm. In
      simultaneous determinations, the ratio of Sr to Ca moved was exactly equal to the
      ratio of their concentrations in nutrient solution, and there was no evidence of
      discrimination. Dinitrophenol reduced transport of Sr and Ca to an equivalent
      extent, amounting to between 2 and 9% of non-treated control levels.

PMID- 16656550
TI  - Further studies of the heat transfer from a leaf.
AB  - The resistance to the diffusion of heat and water vapor external to a leaf, can
      be derived from measurement of the rate of change of the leaf temperature, after
      a sudden alteration of the intensity of irradiation. The theory of the method has
      been developed to accommodate the case of a leaf that is freely transpiring,
      exchanging longwave radiation with the environment and with different internal
      resistances on the 2 sides of the leaf. It has been successfully applied to
      measurements on wet blotting paper in the laboratory.

PMID- 16656551
TI  - Inositol Metabolism in Plants. IV. Biosynthesis of Apiose in Lemna and
      Petroselinum.
AB  - The biosynthesis of apiose was investigated in cell wall polysaccharide of Lemna
      gibba G3 (duckweed) and in detached leaves of Petroselinum crispum (parsley).
      Lemna grown either in short days or in continuous light incorporated (14)C from a
      medium containing myo-inositol-2-(14)C into d-apiosyl and d-xylosyl units of cell
      wall polysaccharides. Labeled d-apiose was characterized by paper chromatography,
      by formation of labeled crystalline di-O-isopropylidene d-apiose, and by gas
      chromatography of trimethylsilyl derivatives of apiose and of its sodium
      borohydride reduction product, apiitol. Periodate oxidation of labeled apiose
      revealed 86 to 94% of the (14)C was located in formaldehyde fragments
      corresponding to C3' and C4. Comparison of this result with work reported by
      Grisebach and Doebereiner and by Beck and Kandler supports the conclusion that
      myo-inositol-2-(14)C was converted to d-apiose labeled specifically at C4.When l
      arabinose-l-(14)C was supplied to Lemna, both l-arabinosyl and d-xylosyl units of
      cell wall polysaccharides became labeled, but no (14)C was found in d-apiose.
      Analysis of the medium external to the plants revealed the presence of a
      polysaccharide-like polymer that also contained labeled xylose and
      arabinose.Petroselinum leaves utilized myo-inositol-2-(3)H for the synthesis of
      apiose in apiin.These results provide direct evidence for a pathway of apiose
      biosynthesis involving d-glucuronic acid metabolism.

PMID- 16656552
TI  - Proserpinaca: photoperiodic and chemical differentiation of leaf development and
      flowering.
AB  - Proserpinaca palustris L. produced juvenile leaves on 8-hour photoperiods, adult
      leaves on 12-hour photoperiods, and adult leaves and flowers on 14-hour
      photoperiods. Treatment of plants growing on 8- and 14-hour photoperiods with
      gibberellic acid caused stem elongation and inhibited flowering. The treated
      plants on 8-hour photoperiods produced adult-like leaves.

PMID- 16656553
TI  - A possible role of hydroxyproline-containing proteins in the cessation of cell
      elongation.
AB  - Hydroxyproline-containing proteins increase markedly in the cell walls of the
      Alaska pea epicotyl during the transition of rapidly elongating tissue into non
      elongating, mature tissue. The increase in these proteins may be a factor in the
      cessation of cell elongation.

PMID- 16656554
TI  - Action spectrum for an enhancement of endogenous respiration by light in
      chlorella.
AB  - The oxygen consumption of a starved chlorophyll-free, yellow mutant of Chlorella
      vulgaris is enhanced by very small amounts of blue light (lambda 450 mmu); a
      saturation level is reached at about 500 ergs cm(-2) sec(-1). At that intensity
      the respiration is about 3 times greater than in the dark. An action spectrum for
      the enhancement of respiration shows 2 peaks around lambda 450 and 375 mmu.
      Flavins and cis-carotenoids are discussed as the pigments involved.

PMID- 16656555
TI  - Kinetics of growth retardant and hormone interactions in affecting cucumber
      hypocotyl elongation.
AB  - The capacities of indole-3-acetic acid (IAA) and gibberellin A(3) (GA(3)) to
      counteract the inhibitory effects of (2-chloroethyl) trimethylammonium chloride
      (CCC), 2-isopropyl-4-dimethylamino-5-methylphenyl-1-piperidinecarboxylate methyl
      chloride (Amo-1618), and N,N-dimethylaminosuccinamic acid (B-995) on hypocotyl
      elongation in light-grown cucumber (Cucumis sativus L.) seedlings were
      investigated. One mug of GA(3) applied to the shoot tip was sufficient to
      completely nullify the effect of 10 mug of Amo-1618 or 25 mug of B-995 applied
      simultaneously to the shoot tip, and 10 mug of GA(3) completely counteracted the
      effect of 10(-3)m CCC added to the root medium. One mug of IAA counteracted the
      effect of 10(-3)m CCC in the root medium, but IAA did not nullify the action of
      either Amo-1618 or B-995. Experiments were conducted using 2 growth retardants
      simultaneously, which indicated that Amo-1618 and CCC inhibit a common process,
      namely GA biosynthesis, essential to hypocotyl elongation. However, since the
      effect of CCC was overcome by applications of both GA and IAA, growth retardation
      resulting from treatment with CCC apparently is not due solely to inhibition of
      GA biosynthesis. B-995 did not interact additively with either Amo-1618 or CCC,
      which suggests that B-995 affects a process different from those affected by the
      other 2 retardants. Thus, while inhibition evoked by B-995 is reversible by
      applied GA, the action of B-995 does not appear to be inhibition of GA
      biosynthesis.

PMID- 16656556
TI  - Steady State Sodium and Rubidium Effluxes in Pisum sativum Roots.
AB  - Steady state effluxes of potassium and sodium ions were measured on Pisum sativum
      var. Alaska root segments excised from seedlings which had grown in a nutrient
      solution containing the major inorganic ions and either (86)Rb as a tracer for K
      or (22)Na as a tracer for Na. Fluxes appeared to be from 2 cellular compartments,
      a small compartment with a high flux rate and a larger compartment with a slow
      flux rate. Cell wall exchange fluxes are believed to have been negligible. Efflux
      rates for 11.3% and 88.7% of cellular potassium ions were 6 x 10(-7) and 1.32 x
      10(-7) respectively; rates for 33.7% and 66.3% of cellular sodium ions were 1.48
      x 10(-7) and 3.83 x 10(-8) respectively, (equivalents per gram fr wt per hr). The
      sodium flux measurements, with previous measurements of ionic concentrations and
      transmembrane potentials, support the theory that sodium is transported actively
      from Pisum roots.

PMID- 16656557
TI  - Inhibition of oxidative phosphorylation and respiration by ozone in tobacco
      mitochondria.
AB  - Ozone was found to inhibit oxidative phosphorylation and oxygen uptake in
      mitochondria of tobacco leaves (Nicotiana tabacum, L. var. White Gold). The
      inhibition appeared to occur at both substrate and electron-transport chain
      levels. The inhibition increased with the length of exposure to ozone, however,
      the phosphorylative system was more sensitive to ozone than the respiratory
      system. With mitochondria from detached leaves after being treated with ozone at
      1 ppm for 1 hour, uncoupling of phosphorylation was demonstrated without any
      detectable change in the rate of respiration in the early stage of ozone effect.
      Inhibition of phosphorylation by ozone was also demonstrated in isolated
      mitochondria without apparent change in optical density of the mitochondrial
      suspension at 520 mmu. Therefore, mitochondrial swelling appears not to be a
      necessary first step for ozone-induced uncoupling of phosphorylation. The
      evidence suggests that inhibition of oxidative phosphorylation in mitochondria
      may be a primary effect of ozone in tobacco leaves.Sucrose and glucose, when fed
      to the detached tobacco leaves before ozone treatment, tended to raise the
      phosphorylative activity of mitochondria. Mannitol and lactose were less
      effective.

PMID- 16656558
TI  - On the localization of organic acids in Acid-induced ATP synthesis.
AB  - This study of the penetration and localization in isolated chloroplasts of some
      selected organic acids under inducing and non-inducing conditions has shown that
      there are 4 distinct relationships of acid penetration to ATP synthesis. Succinic
      acid which is effective as an inducer penetrates quite rapidly at pH 4.0 with the
      time course coinciding with that of acid-poise as determined by ATP synthesis. As
      the pH of stage I is raised (acid more dissociated) the penetration is slower,
      and the internal concentration at equilibrium is less. At pH 6.5 where succinic
      acid is fully dissociated there is little or no penetration of the dianion. A
      portion of the succinic acid (presumably the dianion) is retained in the
      chloroplasts on pH transition. This internal acid can be removed by placing
      plastids back in solution whose pH is less than 5.A relatively ineffective
      dicarboxylic acid, e.g. malonic, penetrates quite slowly at pH 4.0. The acid
      poise is maximized and declines (possibly due to acid denaturation of
      phosphorylating enzymes) much before the internal malonate is maximal. This
      dicarboxylic acid also shows little penetration as the dianion and some of it is
      effectively retained on pH transition from 4.0 to 8.4.Acetic, an ineffective
      acid, penetrates quite well both as the acid and the anion and is not retained as
      the anion on transition from pH 4.0 to 8.4.Glutamic acid which produces ATP
      yields comparable to those obtained with HCl was found to penetrate very slowly
      and did not reveal a measurable amount of retained acid on transition from pH 4.0
      to 8.4.

PMID- 16656559
TI  - Organic Acid specificity for Acid-induced ATP synthesis by isolated chloroplasts.
AB  - A study has been made of the structural requirements for organic acids that
      increase the yield of ATP formed by spinach chloroplasts in the dark due to an
      acid-base transition. Dicarboxylic acids of 4 and 5 carbon atoms with 1 pKa in
      the range of 4.2 to 4.4 and the second at 5.3 to 5.5 are most effective. A fairly
      good correlation was found between the fraction of the acid completely
      undissociated at the test pH and the final yield. Other considerations are also
      important, however, since introducing hydroxyl groups or excessive chain length
      decreased yields in spite of pKa considerations. Aromatic acids, except for the
      dicarboxylic phthalic acids, were inhibitory. The diversity of organic acids
      having some effect makes it unlikely that they serve as substrate for a
      chloroplast enzyme system.

PMID- 16656560
TI  - CO(2) Metabolism in Corn Roots. I. Kinetics of Carboxylation and Decarboxylation.
AB  - The kinetics of (14)CO(2) carboxylation and decarboxylation in corn root tips
      were determined to ascertain the sequence of product formation and subsequent
      utilization, and to obtain further evidence to predict the enzymes mediating the
      carboxylation and decarboxylations. The carboxylation data indicated that the
      first product was oxaloacetate followed by malate and aspartate. Malate was the
      first stable product which could be detected. Decarboxylation data indicated that
      a large fraction of the (14)CO(2) release and turnover of (14)C was accountable
      for by a decrease in malate: however, essentially all labeled amino acids turned
      over rapidly and at a greater rate than organic acids. The data generally support
      the hypothesis that CO(2) fixation in corn root tips is via P-enolpyruvate
      carboxylase and malic dehydrogenase and that subsequent malate metabolism is for
      the most part by direct decarboxylation, possibly by the malic enzyme.

PMID- 16656561
TI  - CO(2) Metabolism in Corn Roots. II. Intracellular Distribution of Enzymes.
AB  - Three enzymes assumed to mediate CO(2) metabolism in corn root tips, P
      enolpyruvate carboxylase, malic dehydrogenase, and the malic enzyme, were
      extracted to determine their relative specific activities and their partitioning
      between soluble and particulate fractions. The data indicated that the
      intracellular location of these 3 enzymes is nonparticulate and thus these
      enzymatic reactions of CO(2) metabolism are apparently nonparticulate. The
      soluble malic dehydrogenase fraction differed from the particulate fraction in
      several kinetic properties, viz., response to the thionicotinamide analog of
      nicotinamide-adenine dinucleotide, oxaloacetate substrate inhibition at pH 8.3,
      and Km's for nicotinamide-adenine dinucleotide and l-malate. It was concluded
      that the soluble-malic dehydrogenase differed from the particulate forms in both
      structure and function. The soluble malic dehydrogenase is apparently involved in
      CO(2) metabolism.

PMID- 16656562
TI  - Studies of the Involvement of an Endogenous Rhythm in the Photoperiodic Response
      of Hyoscyamus niger.
AB  - An attempt was made to determine the involvement of an endogenous circadian
      rhythm in the flowering response of the long-day plant Hyoscyamus niger L. grown
      in a modified White's medium. Both variable-cycle-length and light interruption
      experiments were employed in this attempt. In the variable-cycle experiments,
      plants were subjected to light periods of 6, 12, or 18 hours followed by varying
      lengths of darkness. The total lengths of the cycles varied from 12 to 72 hours.
      In experiments utilizing a 6-hour photoperiod, a high level of flowering occurred
      in cycle lengths of 12, 36, and 60 hours. Flowering was suppressed in the 24-, 48
      , and 72-hour cycles. When a 12-hour photoperiod was used the flowering response
      was low between 24 and 36 hours and flowering did not indicate a rhythmic
      response. When an 18-hour photoperiod was used, the flowering response was
      suppressed in the 36- and 60-hour cycles.Light-break experiments were conducted
      to study further the flowering response in Hyoscyamus. These experiments
      consisted of a 6-hour main photoperiod followed by varying lengths of darkness to
      make cycles of 24, 48, and 72 hours. At given intervals the dark period was
      interrupted by 2-hour light breaks. In a 24-hour cycle, flowering was promoted
      when a light break was given at either the twelfth or eighteenth hour of the
      cycle. In a 48-hour cycle, flowering was strongly promoted by light breaks given
      near the beginning or at the end of the dark period. In a 72-hour cycle, light
      breaks given at the eighteenth, forty-second, and sixty-sixth hour of the cycle
      stimulated flowering as compared with light breaks given at the thirtieth and
      fifty-fourth hour. These results are indicative of the involvement of an
      endogenous rhythm in the flowering response of Hyoscyamus niger.

PMID- 16656563
TI  - Chloroplastic ribosome formation: inhibition by 3-amino-1,2,4-triazole.

PMID- 16656564
TI  - Absence of a Causal Relationship between Auxin-Induced Growth and Changes in the
      Content of Ascorbic and Dehydroascorbic Acids in Excised Plant Tissues.
AB  - The data reported indicate that the oxidation-reduction balance of the ascorbic
      acid system is not causally related to the auxin-regulation of cell elongation.
      There was no shift in the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio
      with growth-promoting concentration of auxin in several plant tissues. The AA to
      DHA ratio was experimentally increased without altering the growth rate.
      Inhibition of growth by supra-optimal auxin was associated with a decrease in the
      AA to DHA ratio. Since the AA to DHA ratio was lowered by EDTA treatment without
      altering growth, it seems unlikely that the decrease in the AA to DHA ratio
      related to the inhibition of growth by high levels of auxin.

PMID- 16656565
TI  - Polar transport characteristics of radiostrontium and radiocalcium in isolated
      corn root segments.

PMID- 16656566
TI  - Time course of low temperature inhibition of sucrose translocation in sugar
      beets.
AB  - Further studies are presented characterizing the time-course response of sucrose
      translocation in sugar beet (Beta vulgaris L. cv Klein Wanzleben) to low
      temperature inhibition. Only the temperature of a 2 cm zone of the source-leaf
      petiole was varied (1 degrees vs 25 degrees , approximately). The half-time of
      inhibition, defined as the time required for 50% inhibition of the control or pre
      cooling rate, varied from 4 to 15 minutes, and the half-time of recovery from 30
      to 100 minutes. Maximum inhibition varied from 68 to 92%. Possible uncertainties
      in evaluating these parameters are discussed. When the duration of the low
      temperature period was sufficient to permit essentially full recovery, subsequent
      re-warming of the petiole zone to 25 degrees to 30 degrees effected little or no
      increase in the translocation rate. It is evident that the interposition between
      source and sink of a 2 cm petiole zone maintained at a temperature generally
      inhibitory to physiological processes resulted in little or no impairment to the
      translocation process, after a suitable thermal adaptation period. Thermally
      adapted petiole systems de-adapted after periods as short as 1 hour at 25 degrees
      .

PMID- 16656567
TI  - Growth and respiration patterns of snap bean fruits.
AB  - The relationship of respiration and growth of seed, pericarp tissue and whole
      fruit of snap beans (Phaseolus vulgaris L.) was studied. The whole fruit
      exhibited an apparent climacteric type of respiration pattern. This pattern
      resulted from an increase in CO(2) production by the enlarging seed followed by a
      rapid decrease in CO(2) evolution by the pericarp tissue, and the pattern was not
      associated with any concomitant increase in ethylene production. Therefore, the
      apparent climacteric respiration pattern of a developing bean fruit is not
      comparable to the phenomenon that occurs in other ripening fruits.

PMID- 16656568
TI  - Isolation of phytochrome from the alga mesotaenium and liverwort sphaerocarpos.
AB  - Phytochrome has been isolated from the green alga Mesotaenium and the liverwort
      Sphaerocarpos. The Mesotaenium pigment had absorption peaks at 649 and 710 nm for
      the P(R) and P(FR) forms, respectively. Corresponding difference spectrum maxima
      for the Sphaerocarpos pigment were at 655 and 720 nm. While the absorption maxima
      differ, the reversibility and efficiency with which red and far-red light
      transform the Mesotaenium pigment are very similar to that reported for
      phytochrome isolated from etiolated seedlings of higher plants. Methods are
      described which allow efficient separation of phytochrome from highly pigmented
      light-grown material.

PMID- 16656569
TI  - Tumor and teratoma induction in tobacco plants by debudding.
AB  - Stem and root tumors and teratomata may be induced in tobacco plants (Nicotiana
      tabacum L., var. One Sucker) by total debudding. Intact plants or plants only
      decapitated produced no tumors or teratomata throughout their life time. These
      findings suggest a possibly important oncological relationship between normal
      growth and tumorous growth. Prevention of normal regeneration (apical and
      axillary shoot growth) incites pathological regeneration (formation of tumors and
      tumor shoots). Total bud killing or inactivation by ionizing radiation did not
      incite tumor or teratoma formation.

PMID- 16656570
TI  - Control of chlorophyll production in rapidly greening bean leaves.
AB  - The possible involvement of nucleic acid and protein synthesis in light-regulated
      chlorophyll formation by rapidly greening leaves has been studied.Removing leaves
      from illumination during the phase of rapid greening results in a reduction in
      the rate of pigment synthesis; cessation occurs within 2 to 4 hours. Etiolated
      leaves which exhibit a lag in pigment synthesis when first placed in the light do
      not show another lag after a 4 hour interruption of illumination during the phase
      of rapid greening.Actinomycin D, chloramphenicol, and puromycin inhibit
      chlorophyll synthesis when applied before or during the phase of rapid greening.
      Application of delta-amino-levulinic acid partially relieves the inhibition by
      chloramphenicol.It is suggested that light regulates chlorophyll synthesis by
      controlling the availability of delta-aminolevulinic acid, possibly by mediating
      the formation of an enzyme of delta-aminolevulinate synthesis. This process may
      result from gene activation or derepression; the involvement of RNA synthesis of
      some sort is suggested by the inhibitory effect of actinomycin D on chlorophyll
      production by rapidly greening leaves.

PMID- 16656571
TI  - Studies on the regeneration of protochlorophyllide after brief illumination of
      etiolated bean leaves.
AB  - The effects of various inhibitors of nucleic acid and protein synthesis on
      protochlorophyllide synthesis in dark-grown Phaseolus vulgaris var. Red Kidney
      have been studied. Actinomycin D, chloramphenicol, and puromycin inhibit the
      regeneration of protochlorophyllide holochrome (detected as a 650 mmu absorption
      peak) in vivo in darkness after photoconversion of endogenous protochlorophyllide
      a to chlorophyllide a; this inhibition does not occur in similarly treated leaves
      supplied with delta-aminolevulinic acid.These data suggest that the regeneration
      of protochlorophyllide results from the synthesis of RNA and enzymes required for
      the production of delta-aminolevulinate.

PMID- 16656572
TI  - Effects of Phosfon-S on Nucleic Acid Metabolism in Pisum sativum Alaska.
AB  - Phosfon-S, a substance which inhibits stem elongation, alters nucleic acid
      metabolism in Pisum sativum Alaska. Methylated albumin kieselguhr (MAK) columns
      were used to fractionate (32)P-labeled nucleic acids. Phosfon-S treatment of the
      plants resulted in a decrease in soluble RNA and an increase in ribosomal RNA.
      Specific activities of the various nucleic acid fractions were lower as a result
      of treatment. The nucleic acids from treated tissues were more resistant to RNase
      degradation, and endogenous RNase activity was lower in treated tissues. When
      RNase treated nucleic acids were fractionated on MAK columns, the DNA-RNA
      fractions from treated plants had a higher specific activity than that of the
      control, which was not true before nuclease treatment. Spectrophotometric
      examination of this fraction revealed a difference in absorption spectra,
      possibly indicating a Phosfon-S nucleic acid complex. It is suggested that these
      alterations in nucleic acid metabolism could in turn alter a wide variety of
      metabolic processes, resulting in retarded growth.

PMID- 16656573
TI  - Hormonal control of proteinase activity in squash cotyledons.
AB  - A crude proteolytic enzyme preparation which hydrolyzes casein was isolated from
      the cotyledons of squash seedlings. The presence of ethylene diamine tetraacetate
      or cysteine did not appreciably affect the activity of the preparation. During
      the course of germination, the level of proteolytic activity increased in the
      cotyledons of intact embryos through the third day and then decreased. The
      presence of the embryonic axis during the first 32 hours of germination was a
      prerequisite for the development of maximum proteolytic activity.The presence of
      a cytokinin, such as benzyladenine, kinetin, BTP [6-(benzylamino)-9-(2
      tetrahydropyranyl)-9H-purine], or phenyladenine, in the culture solution could
      reproduce the effect of the embryonic axis. Other growth regulators did not
      produce this stimulation. High concentrations (1 mm) of all growth regulators
      examined were inhibitory. Various combinations of growth regulators failed to
      produce any synergistic effects. 6-Methylpurine inhibited the development of
      proteinase activity, and this inhibition was only partially restored by
      benzyladenine.A proteinase was partially purified from the cotyledons of 2-day
      old squash seedlings and its synthesis was shown to be under the control of the
      embryonic axis.

PMID- 16656574
TI  - Protein bodies of the soybean.
AB  - Some microscope observations of the protein bodies of the cotyledon cells of the
      soybean (Glycine max) are described, together with changes in their appearance
      which occur on germination. Density gradient centrifugation permits the isolation
      of protein bodies from soymeal. They contain about 70% of the protein of the
      bean. Only 1 protein could be detected in them: glycinin, the major soybean
      protein.The protein bodies were fractionated to light and heavy fractions. The
      former contained 97.5% protein, the latter 78.5%. RNA, phytic acid and lipids
      were also present. The 2 fractions probably differ only in the extent of
      contamination by other cell fragments.

PMID- 16656575
TI  - H-thymidine incorporation into nuclear DNA of leaf cells.
AB  - The incorporation of (3)H-thymidine into nuclear DNA of leaf cells of Nanthium
      pennsylvanicum was studied as a function of concentration and specific activity
      of the radioisotope. From the assessment of the average number of grains per
      nucleus and the percent of labeled nuclei, it was concluded that the
      incorporation was a linear function of concentration of the exogenous
      radioisotopic solution and a logarithmic function of the incubation time. Ten
      microcuries per milliliter on the average yielded 20% of labeled nuclei with 18
      grains per nucleus. Seven-fold increase in concentration only doubled the amount
      of (3)H-thymidine incorporated. The lamina regions near the vein incorporated a
      significantly greater amount of the radioisotope than the lamina region at some
      distance from the vein. The specific activities of 2, 3.35, 6.7 and 15.3 c/mmole
      had no effect upon the amount of (3)H-thymidine incorporated, if the amount of
      microcuries of the incubation solution was the same in each activity. Considering
      the total number of molecules, the estimated rates of incorporation indicated
      that at the activity of 2 c/mmole, the system operated with about 7 times higher
      rates as compared with the activity of 15.3 c/mmole.

PMID- 16656576
TI  - Carbon dioxide and the reduction of indophenol and ferricyanide by chloroplasts.
AB  - Pea chloroplasts isolated in salt media show decreased rates of 2:6
      dichlorophenolindophenol (DCPIP) and ferricyanide reduction when depleted of
      CO(2) at pH values below 7.5. The greatest effect of CO(2) was on uncoupled
      systems. The incorporation of 10(-2), 2 x 10(-2) and 4 x 10(-2)m sodium acetate
      into the reaction mixtures progressively increased the bicarbonate concentration
      required for half maximal rates of reduction of DCPIP. The reaction was saturated
      by bicarbonate concentrations of 1 to 4 x 10(-2)m. With both DCPIP and
      ferricyanide, the addition of bicarbonate to illuminated chloroplast systems
      depleted of CO(2) gave very rapid increases in the rates of reduction.
      Bicarbonate also stimulated oxygen uptake by the illuminated chloroplasts when
      added hydrogen acceptors had been reduced. There was no effect of bicarbonate on
      ferricyanide reduction at low light intensities, but with DCPIP reduction, the
      apparent magnitude of the effect was independent of light intensity. This
      suggests that DCPIP reacts with the chloroplast electron transport chain at a
      site nearer to a photochemical stage than does ferricyanide. It also suggests
      that CO(2) has at least 2 sites of action.

PMID- 16656577
TI  - Intracellular Distribution of p-Nitrophenyl-Phosphatase in Plants.
AB  - Less than 10% of the acid p-nitrophenylphosphatase activity of plant extracts was
      sedimentable under a variety of conditions including zonal centrifugation. The
      sedimentable fraction did not show the latency properties characteristic of
      animal lysosomes. We conclude that, at least operationally, plant acid
      phosphatase is a soluble enzyme and that it is not suitable as a lysosomal
      marker. The plant tissues employed were pea cotyledons, cauliflower florets,
      turnip storage organs, onion embryos, and leaves of red oak and soybean.

PMID- 16656578
TI  - Dependence of Basipetal Polar Transport of Auxin upon Aerobic Metabolism.
AB  - The movement of IAA-(14)C through coleoptile segments of Avena and Zea has been
      investigated under aerobic and anaerobic conditions. The results are as follows:
      Zea. Using a 5-mm segment and a 2-hour transport period anaerobic conditions
      reduced the total uptake of (14)C from an apical donor by 74% and the proportion
      of the total found in the receiving block by at least 45%. Anaerobic conditions
      reduced total uptake from a basal donor by 58% but no (14)C reached the apical
      receiving block in either air or N(2). Uptake from apical and basal donor blocks
      in N(2) is closely similar.The presence of (14)C in the basal receiving blocks,
      and its absence in the apical receiving blocks, in N(2) suggests that even in
      anaerobic conditions movement of IAA is polarized basipetally, although the
      movement occurs at only a fraction of the rate found in air.Anaerobic conditions
      induced a similar reduction in basipetal movement of IAA in upper and lower 5-mm
      segments taken from the apical 10 mm of a Zea coleoptile.Using 10-mm Zea segments
      no (14)C was recovered in the receiving blocks at the basal end of the segment
      after 2 and 4 hours in N(2) whereas large amounts were recovered in air.Avena:
      Using 5-mm segments and a 2-hour transport period the total uptake of (14)C from
      an apical donor is reduced by 83%. Movement of (14)C into the basal donor is
      totally inhibited in N(2). Total uptake of (14)C from a basal donor is reduced by
      61% in nitrogen and no (14)C reached the apical receiving blocks regardless of
      the atmospheric conditions.A time course for the movement of (14)C into the basal
      and apical receiving blocks through 5-mm segments showed that in air the amount
      in the basal receivers increased for 4 hours and then remained approximately
      uniform. In N(2) no significant (14)C reached the receivers until 6 to 8 hours
      after the application of donors but even then the amounts were about 12 to 14% of
      that in aerobic receivers. Movement of (14)C into apical receivers was similar in
      air and in nitrogen and even after 6 to 8 hours the amount of radioactivity
      barely reached significant levels.

PMID- 16656579
TI  - Sucrose as a product of photosynthesis in isolated spinach chloroplasts.
AB  - Sucrose has been detected as a seasonal photosynthetic product in spinach
      chloroplast preparations. Sucrose when present accounted for up to 30% of the
      CO(2) fixed. Experiments in which sucrose was formed have been compared with
      experiments in which it was not formed, and a possible control mechanism for
      sucrose synthesis is discussed.

PMID- 16656580
TI  - Physiological Studies on Pea Tendrils. III. ATPase Activity and Contractility
      Associated with Coiling.
AB  - Extracts of the tendrils of Pisum sativum, Var. Alaska, exhibit adenosine
      triphosphatase activity which is inversely proportional to the amount the
      tendrils have coiled. The specific viscosity of the extract decreases when ATP is
      added. This evidence indicates a possible role of a contractile adenosine
      triphosphatase in coiling.

PMID- 16656581
TI  - Physiological Studies on Pea Tendrils. IV. Flavonoids and Contact Coiling.
AB  - Pea tendrils contain high concentrations of flavonoids, mainly quercetin
      triglucosyl-p-coumarate (QGC). QGC is most abundant near the highly responsive
      apex of the tendril, and least abundant at the base. After mechanical
      stimulation, and during coiling of the tendril, the QGC titer drops to about 30%
      of its original value. The kinetics of flavonoid disappearance are significantly
      correlated with the kinetics of coiling.Aqueous extracts of unstimulated pea
      tendrils or 10 mum QGC inhibit contact coiling of excised tendrils. Extracts of
      coiled tendrils do not. The evidence indicates a possible regulatory role for
      flavonoids in contact coiling.

PMID- 16656582
TI  - Analysis and distribution of tocopherols and quinones in the pea plant.
AB  - A procedure is described and evaluated for the analysis of ubiquinone,
      plastoquinone, tocopherols and vitamin K(1) in Pisum sativum L. Vitamin K(1)
      appears to be absent from the roots of this plant. While the pea seed contains
      only gamma-tocopherol, the root and shoot contain only alpha-tocopherol. During
      the greening of etiolated tissue, plastoquinone and vitamin K(1) levels increase
      markedly while ubiquinone and alpha-tocopherol levels are unaffected. On
      homogenization or damage to tissue, considerable losses of alpha-tocopherol occur
      in the pea plant.

PMID- 16656583
TI  - Uptake and metabolism of vitamins e and k by pea stem sections.
AB  - The uptake of alpha-tocopherol and vitamin K(1) by pea stem sections is
      described. Vitamin K(1) appears to be stable within the plant tissue and is found
      distributed in all particulate cell fractions following uptake. Only a small
      proportion of the tocopherol taken up is recoverable and the majority of the
      compound appears to undergo catabolism.The oxidation of tocopherols by a cell
      free system is described. This system requires oxygen and appears to involve
      enzyme activity but does not appear to be linked with the action of lipoxidase.

PMID- 16656584
TI  - Polar transport related to mobilization of plant constituents.
AB  - Indole-3-acetic acid (IAA), 2-methoxy-3,6-dichlorobenzoic acid (dicamba),
      sucrose, and mannitol, were tested for polar transport through 5-mm hypocotyl
      segments of bean (Phaseolus vulgaris var. Pinto) seedlings. All 4 compounds were
      transported in a polar direction. Autoradiographs of segments through which (14)C
      labeled compounds were transported indicated areas of (14)C concentration near
      the morphological base of segments. There was a direct correlation of IAA
      transport with the ability to initiate roots as well as with the degree of (14)C
      accumulation in the morphological base of segments. Unlabeled IAA in lanolin
      applied to segments appeared to reduce transport of IAA-(14)C through those
      segments when measured by the accumulation of (14)C in a receiver-block of agar,
      caused an increase in (14)C accumulation in the region to which the unlabeled IAA
      was applied, and also caused a decrease in accumulation of (14)C at the
      morphological base of upright segments. Histological studies showed that IAA
      accelerated cell division and the formation of root primordia particularly at the
      basal ends, and that these responses sometimes occurred at the expense of cell
      proliferation at the apical ends of segments. The data presented support the
      hypothesis that polar movement of IAA, and other endogenous and exogenous
      substances, in isolated stem segments was controlled by mobilization and
      utilization of plant constituents at the growth centers.

PMID- 16656585
TI  - Rotation axes for analysis of gravity effects on plant organs.
AB  - Epinastic curvatures of branches of Coleus blumei Benth. and the growth pattern
      of wheat (Triticum aestivum L.) seedlings on clinostats were used for bioassay of
      rotation methods for preventing growth responses to gravity. Tumbling a plant end
      over end was found to be just as effective as rotation about its horizontal axis.
      The results support the reliability of data from experiments in which an entire
      plant is rotated about a single horizontal line with only part or none of its
      immature tissues in horizontal orientation to gravity.

PMID- 16656586
TI  - Translocation of Sugars in Cucurbita melopepo IV. Effects of Temperature Change.
AB  - A study has been made of the temperature control of translocation localized to
      regions of the stem, petiole and hypocotyl of Cucurbita melopepo. The basipetal
      and acropetal movement of translocated (14)C-labeled compounds in the phloem
      tissue, measured over a 45-minute period, was almost completely inhibited at 0
      degrees . At 10 degrees a partial inhibition occurred while an extremely variable
      degree of inhibition occurred at 15 degrees . Above 15 degrees to 35 degrees
      temperature ceased to be a limiting factor in the movement of (14)C-labeled
      compounds. At 45 degrees partial inhibition was observed while at 55 degrees
      there was an almost complete cessation. The localized temperature treatment of
      the plant parts did not disturb the rate of (14)CO(2) assimilation or the export
      of (14)C compounds by the leaf blade. Translocated compounds unable to pass a
      temperature inhibited zone were diverted toward other importing regions of the
      plant. The similarity of the translocation response to temperature change in the
      various organs of the plant indicated a uniform mechanism throughout the plant
      controlling movement of the major proportion of the translocated compounds. The
      temperature characteristics of the mechanism were found to closely parallel those
      of protoplasmic streaming in chill-sensitive plants.

PMID- 16656587
TI  - Inhibition and promotive effects of desoxygibberellin C and its methyl ester on
      plant growth.

PMID- 16656588
TI  - Induction of Light Sensitive Dormancy in Seed of Lactuca sativa L. (Lettuce) by
      Patulin.

PMID- 16656589
TI  - Lateral auxin transport in stems and roots.

PMID- 16656590
TI  - Hormonal control of enzyme synthesis: on the mode of action of gibberellic Acid
      and abscisin in aleurone layers of barley.
AB  - Gibberellic acid (GA) enhances the synthesis of alpha-amylase and ribonuclease in
      isolated aleurone layers and this process is inhibited by abscisin. Removal of
      gibberellic acid in mid-course of alpha-amylase production results in a slowing
      down of alpha-amylase synthesis, suggesting a continued requirement of GA for
      enzyme synthesis. This is paralleled by a continuous requirement for RNA
      synthesis. Addition of 6-methylpurine or 8-azaguanine in mid-course results in an
      inhibition of alpha-amylase synthesis within 3 to 4 hours. However, actinomycin D
      added in mid-course is almost without effect. This is not due to its failure to
      enter the cells, because it does inhibit (14)C-uridine incorporation at this
      stage. Addition of abscisin to aleurone layers which are synthesizing alpha
      amylase results in an inhibition of this synthesis within 2 to 3 hours.
      Cycloheximide on the other hand inhibits enzyme synthesis immediately upon its
      addition. These data are consistent with the hypothesis that the expression of
      the GA effect requires the synthesis of enzyme-specific RNA molecules. The
      similarity in the kinetics of inhibition between abscisin on the one hand and 8
      azaguanine or 6-methylpurine on the other suggests that abscisin may exert its
      action by inhibiting the synthesis of these enzyme-specific RNA molecules or by
      preventing their incorporation into an active enzyme-synthesising unit.

PMID- 16656591
TI  - Distribution of Three Auxin Protector Substances in Seeds and Shoots of the
      Japanese Morning Glory (Pharbitis nil).
AB  - The existence of substances which inhibit the enzymatic destruction of auxin in
      shoots of the Japanese morning glory (Pharbitis nil Choisy) has been confirmed,
      as has the fact that these substances are distributed in a gradient diminishing
      from apex to base in a manner indicating a regulatory role in internode
      elongation and tissue maturation. In addition to the 2 auxin protector substances
      reported previously (protectors I and II) which appear to account for most of the
      inhibition of the enzymatic destruction of auxin in young, elongating stem
      tissue, a third substance, designated as protector A, has been found to be highly
      active in seeds, and shoot tips of mature plants: In germinating seeds, no
      protector I or II activity was observed; in stem tips, no protector II and only
      slight protector I activity was observed. In contrast, old tissue contained no
      detectable amounts of protector A, but did contain protectors I and II. Between
      these extremes along the shoot axis, mixtures of the 3 substances were found. The
      evidence can be interpreted to mean that protector A is degraded into protectors
      I and II and perhaps translocated in this form. Gel filtration studies indicate
      that protector A has a molecular weight exceeding 200,000 gm/mole.

PMID- 16656592
TI  - Opposing effects of gibberellin and ethylene.

PMID- 16656593
TI  - Soluble proteins in alfalfa roots as related to cold hardiness.
AB  - Soluble proteins extracted from alfalfa roots of hardy and nonhardy varieties
      were studied in relation to cold hardiness with polyacrylamide gel
      electrophoresis and quantitative enzyme analysis. Soluble protein content of
      alfalfa roots increased during hardening in all varieties. Two new isoenzymes
      with peroxidase activities were found in the fully hardened samples but no large
      shifts in the electrophoretic pattern were detected with polyacrylamide gel
      electrophoresis. Peroxidase and catalase activities increased during hardening in
      all varieties, but only small differences among hardy and nonhardy varieties were
      detectable. The studies indicated that protein metabolism was altered during the
      hardening process.

PMID- 16656594
TI  - The specific nature of plant cell wall polysaccharides.
AB  - Polysaccharide compositions of cell walls were assessed by quantitative analyses
      of the component sugars. Cell walls were hydrolyzed in 2 n trifluoroacetic acid
      and the liberated sugars reduced to their respective alditols. The alditols were
      acetylated and the resulting alditol acetates separated by gas chromatography.
      Quantitative assay of the alditol acetates was accomplished by electronically
      integrating the detector output of the gas chromatograph. Myo-inositol,
      introduced into the sample prior to hydrolysis, served as an internal
      standard.The cell wall polysaccharide compositions of plant varieties within a
      given species are essentially identical. However, differences in the sugar
      composition were observed in cell walls prepared from different species of the
      same as well as of different genera. The fact that the wall compositions of
      different varieties of the same species are the same indicates that the
      biosynthesis of cell wall polysaccharides is genetically regulated. The cell
      walls of various morphological parts (roots, hypocotyls, first internodes and
      primary leaves) of bean plants were each found to have a characteristic sugar
      composition.It was found that the cell wall sugar composition of suspension
      cultured sycamore cells could be altered by growing the cells on different carbon
      sources. This demonstrates that the biosynthesis of cell wall polysaccharides can
      be manipulated without fatal consequences.

PMID- 16656595
TI  - Effect of 2'-deoxyadenosine on thymidine utilization by tradescantia pollen
      grains.
AB  - The uptake of (3)H-thymidine into pollen grains of Tradescantia paludosa was
      studied in the presence of 2'-deoxyadenosine. 1) Millimolar deoxyadenosine caused
      an immediate inhibition of incorporation of (3)H-thymidine into DNA extracted
      with hot trichloroacetic acid. 2) The radioactivity in acid-soluble derivatives
      of (3)H-thymidine was examined by paper chromatography and, following incubation
      of pollen grains in the presence of millimolar deoxyadenosine, was found to be
      increased several-fold in (3)H-deoxythymidine triphosphate. 3) The time-course of
      inhibition showed that the acid-soluble derivatives of (3)H-thymidine accumulated
      initially at a rate unaffected by deoxyadenosine, despite the nearly complete
      inhibition of incorporation of (3)H-thymidine into DNA. This is discussed in
      relation to possible mechanisms of inhibition by deoxyadenosine.

PMID- 16656596
TI  - Identification of Indole-3-Acetic Acid in the Basidiomycete Schizophyllum
      commune.
AB  - Indole-3-acetic acid (IAA) was detected in the ether extracts of culture
      filtrates of indigotin-producing strains of the basidiomycete Schizophyllum
      commune. Several solvents, known to give distinctly different R(F) values for
      IAA, and 3 location reagents gave identical results with synthetic IAA and IAA
      found in the extract. Confirmation was obtained by the Avena straight growth
      test, split pea test, and ultraviolet absorption spectrum.

PMID- 16656597
TI  - Some Effects of Sodium on Nitrate Assimilation and N(2) Fixation in Anabaena
      cylindrica.
AB  - Anabaena cylindrica grown with nitrate required higher levels of sodium (0.4
      meq/l NaCl) to prevent chlorosis than when grown without combined nitrogen (0.004
      meq/l NaCl). Nitrite accumulated in sodium-deficient cultures containing nitrate.
      Amounts of nitrite similar to those found in deficient cultures when added to
      normal cultures resulted in a chlorosis of the cells. Thus loss of chlorophyll
      was caused by nitrite toxicity.A deficiency of sodium resulted in an increased
      incorporation of (15)NO(3), (15)NO(2), (15)NH(3) or (14)C glutamate into protein
      compared with normal cells. The enzyme nitrate reductase was markedly increased
      in cells grown without sodium.Evidence from chloramphenicol treatment of the
      cells suggests that sodium may exert its control of nitrate reductase through a
      protein factor(s).By contrast, N(2) fixation was reduced in sodium deficient
      cells. Since the incorporation of ammonia or glutamate into protein was increased
      under these conditions, it is likely that the element is required for the
      conversion of N(2) gas into ammonia. Various nitrogenous compounds including
      ammonium chloride, amides and amino acids at low concentrations (0.1 mm) greatly
      reduced the nitrite accumulation in sodium-deficient cultures.

PMID- 16656598
TI  - RNA metabolism during light-induced chloroplast development in euglena.
AB  - Methods are described which provide good recoveries of non-degraded chloroplast
      and non-chloroplast RNAs from Euglena gracilis var. bacillaris. These have been
      characterized by comparing the RNA from W(3)BUL (an aplastidic mutant of
      Euglena), with that of wild-type cells which have been resolved into chloroplast
      and non-chloroplast fractions. Using E. coli RNA as a standard, the RNAs from
      W(3)BUL and from the non-chloroplast fraction of green cells exhibit optical
      density peaks, upon sucrose gradient centrifugation, at 4S, 10S, and 19S. The
      chloroplast fraction exhibits optical density peaks at 19S and 14S with the 19S
      component predominating. Application of various techniques for the separation of
      RNAs to the problem of separating the chloroplast and non-chloroplast RNAs,
      without prior separation of the organelle, have not proven successful.(32)P(i) is
      readily incorporated into RNA by cells undergoing light-induced chloroplast
      development, and fractionation at the end of development reveals that although
      chloroplast RNAs have a higher specific activity, the other RNAs of the cells are
      significantly labeled as well. The succession of labeling patterns of total
      cellular RNA as light-induced chloroplast development proceeds are displayed and
      reveal that all RNA species mentioned above eventually become labeled. In
      contrast, cells kept in darkness during this period incorporate little (32)P(i)
      into any RNA fraction. In addition, a heavy RNA component, designated as 28S,
      while representing a negligible fraction of the total RNA, becomes significantly
      labeled during the first 24 hours of illumination. While there is light
      stimulated uptake of (32)P(i) into the cells, this uptake is never limiting in
      the light or dark, for RNA labeling.On the basis of these findings, we suggest
      that extensive activation of non-chloroplast RNA labeling during chloroplast
      development is the result of the activation of the cellular synthetic machinery
      external to the chloroplast necessary to provide metabolic precursors for plastid
      development. Thus the plastid is viewed as an auxotrophic resident within the
      cell during development. Other possibilities for interaction at this and other
      levels are also discussed.

PMID- 16656599
TI  - Modification of apparent phytochrome synthesis in pisum by inhibitors and growth
      regulators.
AB  - The repeated exposure of Pisum (pea) plants to red light brings into operation an
      apparent synthesis of phytochrome which is not observed in material kept in the
      dark. This process shows some temperature compensation but has an optimum at 26
      degrees ; it is irreversibly inhibited by 10(-4)m cycloheximide and 10 mug/ml
      actinomycin D. It is also inhibited by the auxins indoleacetic acid, naphthalene
      acetic acid and 2,4-dichlorophenoxyacetic acid at 10(-4)m but in these cases the
      inhibition is completely reversed when the auxin is washed out of the tissue.
      Antiauxins 2,4,6-trichlorophenoxyacetic acid and p-chlorophenoxy isobutyric acid,
      while strongly inhibiting growth have little effect on apparent synthesis. Other
      growth regulators and the precursor of tetrapyrrole synthesis, delta
      aminolevulinic acid, have no consistent effect on the process, but 3 x 10(-4)m
      cobalt (II) nitrate is inhibitory. The capacity for apparent synthesis decreases
      as the cells approach maturity. The results may be explained by either de novo
      synthesis of phytochrome, or by a transformation process resembling in some
      respects the dark reversion of Pfr to Pr. The physiological role of apparent
      synthesis is suggested.

PMID- 16656600
TI  - Biosynthesis of Protein Amino Acids in Plant Tissue Culture IV Isotope
      Competition Experiments using Glucose-U-C and Potential Intermediates.
AB  - The isotope competition method with glucose-U-(14)C as a carbon source has been
      used to determine whether or not selected compounds contribute carbon to the
      biosynthesis of protein amino acids in cells derived from Paul's Scarlet Rose. Of
      48 compounds tested, 15 contributed carbon to protein amino acids. The results
      show for the first time that homoserine is an intermediate in threonine
      biosynthesis; that homoserine, cystathionine and homocysteine are intermediates
      in methionine biosynthesis and that histidinol is an intermediate in histidine
      biosynthesis in plant cells.

PMID- 16656601
TI  - Growth and synthesis of nucleic Acid and protein by excised radish cotyledons.
AB  - Nutritional and light requirements for growth and synthesis of RNA, DNA, and
      protein by cotyledons excised from 5-day-old seedlings of Raphanus sativus L.
      were investigated, and the course of synthesis was followed through the cell
      cycle. The minimum requirements for a net increase in nucleic acid and protein
      were sugar, nitrate, and light. The cotyledons used nitrite at low concentration,
      but not ammonium ion. Light was required for preliminary steps in synthesis of
      RNA, DNA, and protein, but the actual polymerization reactions occurred in the
      dark. The cotyledons contained sufficient endogenous growth factors for about
      half of the cells to complete 1 cycle on a medium of 1% sucrose, 80 mm KNO(3).
      The increase in DNA was limited to about 50% and was accompanied by a comparable
      increase in cell number. Fresh weight, RNA, and protein tended to increase in
      proportion to DNA. Growth of the isolated cotyledons commenced with cell
      enlargement. RNA began to increase after about 4 hours, DNA after about 12. The
      major increase in protein also began at about 12 hours. The maximum rate of
      increase for all 3 occurred between 12 and 16 hours. Cell counts indicated that
      by 28 hours most of the cells which had replicated DNA had also completed cell
      division.

PMID- 16656602
TI  - Ion Absorption and Retention by Chlorella pyrenoidosa. III. Selective
      Accumulation of Rubidium, Potassium and Sodium.
AB  - The selective preference of Chlorella pyrenoidosa for alkali metal cations was
      found to have the order Rb > K > > > Na. It was demonstrated that a cation of
      higher preference can replace in the cell cations of lower preference by an ion
      interchange process.The replacement of Na from the cell by K or Rb occurred
      against high external Na concentrations up to 450 meq/1 Na.It is suggested that
      the structural selectivity of the Chlorella cell may be amplified by a
      chromatographic type repetitive selection process, driven by metabolically
      dependent unsymmetric shape changes of cellular membranes.

PMID- 16656603
TI  - Relatedness Among Plants as Measured by the DNA-Agar Technique.
AB  - An improved method for extraction of plant DNA is described. Quantitative species
      comparisons based on DNA-DNA hybridization are reported for several members of
      the family Leguminosae and for barley, wheat and rye. A maximum of about 10%
      homology in DNA polynucleotide sequences is found between monocotyledons and
      dicotyledons tested, whereas 20 to 90% homology is observed within a family.
      Species compared using a DNA fraction enriched for redundant polynucleotide
      sequences generally appear to be more closely related than when whole DNA is
      used. DNA-DNA hybridization may be useful in systematic and evolutionary study of
      plants, and also as a possible screening procedure for interfertility of species.

PMID- 16656604
TI  - In vitro autolysis of plant cell walls.
AB  - Primary cell walls of Zea mays prepared in a glycerol medium are capable of
      autolysis in vitro. Autolysis results in solubilization of about 10% of the wall
      substance during an 8 hour incubation period. Approximately 10% of the
      solubilized material is glucose and the remainder consists of an unidentified
      polymer which yields only glucose upon hydrolysis. Cell wall autolysis is a
      linear function of time of incubation and of wall concentration. The autolytic
      process occurs optimally over the pH range of 5.5 to 6.5. The possible
      relationship between autolytic capacity and capacity for elongation is discussed.

PMID- 16656605
TI  - Time Course of Steroid Biosynthesis and Metabolism in Haplopappus heterophyllus.
AB  - A single dose of mevalonic acid-2-(14)C was administered simultaneously to 6
      Haplopappus heterophyllus plants. They were harvested at intervals ranging from 3
      days to 6 months. Four groups of biosynthetically related sterols were found to
      be radioactive in each plant, and the changes in radioactivity with time were
      studied. The most striking finding was a radioactive phenolic material present
      only in the 6-month plant, which had flowered.

PMID- 16656606
TI  - Temperature features of enzymes affecting crassulacean Acid metabolism.
AB  - Enzymes involved in malic acid production via a pathway with 2 carboxylation
      reactions and in malic acid conversion via total oxidation have been demonstrated
      in mitochondria of Bryophyllum tubiflorum Harv. Activation of the mitochondria by
      Tween 40 was necessary to reveal part of the enzyme activities. The temperature
      behavior of the enzymes has been investigated, revealing optimal activity of acid
      producing enzymes at 35 degrees . Even at 53 degrees the optimum for acid
      converting enzymes was not yet reached. From the simultaneous action of acid
      producing and acid-converting enzyme systems the overall result at different
      temperatures was established. Up to 15 degrees the net result was a malic acid
      production. Moderate temperatures brought about a decrease in this accumulation,
      which was partly accompanied by a shift to isocitrate production, while at higher
      temperatures total oxidation of the acids exceeded the production.

PMID- 16656607
TI  - Radial salt transport in corn roots.
AB  - Primary roots of solution-grown, 5-day-old or 6-day-old seedlings of corn (Zea
      mays L.) 10 to 14 cm in length were used to study radial salt transport.
      Measurements were made of the volume of root pressure exudation, salt
      concentration of the exudate, and rate of salt movement into the xylem exudate.
      The (32)P uptake, O(2) consumption, and dehydrogenase activity of the root cortex
      and stele also were studied.These roots produced copious root pressure exudate
      containing 4 to 10 times the concentration of (32)P in the external solution.
      Freshly separated stele from 5-day-old roots accumulated (32)P as rapidly as the
      cortex from which it was separated and the stele of intact roots also accumulated
      (32)P. Separated stele has a higher oxygen uptake than cortex. It also shows
      strong dehydrogenase activity with the tetrazolium test. The high oxygen
      consumption, (32)P uptake and strong dehydrogenase activity indicate that the
      cells of the stele probably play a direct role in salt transport.These data raise
      doubts concerning theories of radial salt transport into the xylem based on the
      assumption that the stele is unable to accumulate salt vigorously.

PMID- 16656608
TI  - Enhanced Dark CO(2) Fixation by Preilluminated Chlorella pyrenoidosa and
      Anacystis nidulans.
AB  - The products of short time photosynthesis and of enhanced dark (14)CO(2) fixation
      (illumination in helium prior to addition of (14)CO(2) in dark) by Chlorella
      pyrenoidosa and Anacystis nidulans were compared. Glycerate 3-phosphate,
      phosphoenolpyruvate, alanine, and aspartate accounted for the bulk of the (14)C
      assimilated during enhanced dark fixation while hexose and pentose phosphates
      accounted for the largest fraction of isotope assimilated during photosynthesis.
      During the enhanced dark fixation period, glycerate 3-phosphate is carboxyl
      labeled and glucose 6-phosphate is predominantly labeled in carbon atom 4 with
      lesser amounts in the upper half of the C(6) chain and traces in carbon atoms 5
      and 6. Tracer spread throughout all the carbon atoms of photosynthetically
      synthesized glycerate 3-phosphate and glucose 6-phosphate. During the enhanced
      dark fixation period, there was a slow formation of sugar phosphates which
      subsequently continued at 5 times the initial rate long after the cessation of
      (14)CO(2) uptake. To explain the kinetics of changes in the labelling patterns
      and in the limited formation of the sugar phosphates during enhanced dark CO(2)
      fixation, the suggestion is made that most of the reductant mediating these
      effects did not have its origin in the preillumination phase.It is concluded that
      a complete photosynthetic carbon reduction cycle operates to a limited extent, if
      at all, in the dark period subsequent to preillumination.

PMID- 16656609
TI  - Studies on the manganese of the chloroplast.
AB  - Manganese deficiency of green plants is known to affect preferentially the
      activity of the oxygen evolving system in the photosynthetic apparatus. Our
      studies showed that the time needed to reactivate photosynthesis in Mn-deficient
      algae varies with each culture, and is often very short when Mn is added not
      before illumination but during the light period. The recent finding by Cheniae
      and Martin that the reactivation requires light, is confirmed. The plain
      incorporation of (54)Mn into deficient algae as distinguished from reactivation
      was barely affected by light, yet was inhibited by uncouplers of phosphorylation.
      Higher plants responded to manganese deficiency either by adjusting the number of
      chloroplasts per cell to the limited Mn supply, or by forming disorganized
      chloroplasts with low chlorophyll content. These 2 types of responses produced
      chlorotic plants which had either a few photosynthetically active or many
      disabled chloroplasts. Photosystem I mediated photophosphorylation turned out to
      be much more sensitive to manganese deficiency than the system I dependent
      photoreduction of NADP(+).

PMID- 16656610
TI  - Thermal conductivity of functional citrus tree wood.
AB  - Thermal conductivity coefficients have been determined for longitudinal and
      transverse flow in 4 varieties of fresh Citrus wood using steady state-methods.
      Equations were developed from which thermal conductivity could be rapidly
      estimated from moisture content or electrical conductivity. The heat balance of
      large and small tree trunks on a freezing night has been calculated on the basis
      of the coefficients.

PMID- 16656611
TI  - Biogenesis of Mitochondria in Germinating Peanut Cotyledons II. Changes in
      Cytochromes and Mitochondrial DNA.
AB  - Biogenesis of mitochondria occurs in the germinating cotyledons of peanuts. This
      process was demonstrated by measuring both constitutive and enzymatic properties
      of mitochondria as a function of germination time. Direct counting by phase
      contrast microscopy of sucrose density gradient preparations showed that the
      number of mitochondria increased markedly during germination. DNA with a buoyant
      density distinct from the major cellular DNA was associated with these
      mitochondrial preparations. During germination the amount of this DNA in
      mitochondrial pellets increased. This increase closely paralleled the increase in
      number of mitochondria.Succinoxidase and succinic dehydrogenase increased during
      germination. Both activities were confined to the mitochondrial fraction. The
      rate of increase of succinoxidase activity was significantly greater than the
      rate of increase of succinic dehydrogenase and both increased at least initially
      at a greater rate than the amount of mitochondrial DNA or numbers of
      mitochondria.The amounts of cytochromes present in mitochondrial preparations
      were measured spectrophotometrically. All of the cytochromes increased in amount
      during germination. The rate of increase of cytochrome a - a(3) very close to the
      rate of increase in succinoxidase activity.

PMID- 16656612
TI  - Respiratory metabolism in buckwheat seedlings.
AB  - Young seedlings of buckwheat (Fagopyrum esculentum) respire in air with an RQ of
      unity. Analysis of respiratory substrates coupled with a study of the utilization
      of acetate-(14)C and glucose-(14)C suggest that both the Embden-Meyerhof-Parnas,
      tricarboxylic acid and pentose phosphate sequences participate in the total
      respiratory catabolism.In anoxia CO(2) dropped to one third of the aerobic rate
      and ethanol accumulated to only about one half the rate of CO(2) output on a
      molar basis. Smaller amounts of lactate, succinate and free amino acids
      (particularly alanine and gamma-aminobutyric acid) accumulated, carboxylic acids
      decreased and there were initial increased in pyruvate and alpha-ketoglutarate.
      The observed changes are consistent with residual tricarboxylic acid and pentose
      phosphate cycle activity in anoxia and may account for the excess CO(2)
      production over ethanol accumulation. CO(2), ethanol and lactate production did
      not account for all of the carbohydrate consumed in anoxia.Relative rates of
      carbon loss were measured in air and in atmospheres containing 3.5%, 2.1%, 1.3%
      and 0.6% oxygen. The extinction point of anaerobic metabolism was 1.5%.On return
      to air from anoxia the CO(2) output increased and the RQ rose from 0.8 to 1.0
      over the first 2-hour period. Ethanol, lactate and succinate were consumed and
      other constituents returned to their previous aerobic level. Some of these
      changes suggest a rather slow resumption of tricarboxylic acid cycle activity on
      return to air.Carbon loss as CO(2) in air was greater than the carbon loss as
      CO(2) at the extinction point. Carbon loss in anoxia as CO(2), ethanol and
      lactate was similar to carbon loss at the extinction point. Assessed in this
      orthodox manner buckwheat seedlings show no Pasteur effect but the complex nature
      of the changes in levels of metabolic substrates and intermediates do not allow
      firm conclusions to be drawn on the effects of oxygen on the rates of glycolysis
      and other respiratory processes.

PMID- 16656613
TI  - Some effects of oxygen concentration on levels of respiratory intermediates in
      buckwheat seedlings.
AB  - Changes in levels of glycolytic and some related respiratory intermediates in
      young seedlings of buckwheat (Fagopyrum esculentum) following transfer A) from
      air to anoxia, B) from air to 1.5% O(2), C) from 1.5% O(2) to anoxia and D) from
      anoxia to air, are recorded and discussed in relation to other measurements made
      with these seedlings.On transfer from air to anoxia the changes are similar to
      those recorded for pea seeds in which it is inferred that glycolysis is faster in
      anoxia than in air. The results with buckwheat however can be explained in terms
      of a decreased rate of glycolysis in anoxia. An alternative hypothesis is
      developed which states that glycolysis is faster in anoxia than in air and that
      it is the contribution of the pentose phosphate cycle to the total respiratory
      catabolism which decreases as the oxygen concentration is reduced towards zero.

PMID- 16656614
TI  - Selective effects of purine and pyrimidine analogues and of respiratory
      inhibitors on perithecial development and branching in sordaria.
AB  - The initiation of perithecia in the homothallic ascomycete Sordaria fimicola was
      completely suppressed, without seriously inhibiting vegetative growth, by growing
      the fungus on an agar medium containing one of the following additions: 1) 1 mum
      5-fluorouracil, 2) 10 to 100 mum 6-azauracil, 8-azaguanine or 8-azaadenine, 3) 50
      to 500 mum cyanide or azide, 4) 5% (w/v) casein hydrolysate. In contrast to the
      selective activity of the analogues of 3 RNA bases, whose inhibition could be
      reversed by the appropriate normal bases only, none of the analogues of thymine
      were active, neither were the thio-derivatives of RNA bases. Other inhibitors of
      RNA and protein synthesis, like actinomycin D, puromycin and cycloheximide, were
      also without selective activity, although the last of these inhibited perithecial
      maturation at 0.1 mum concentration but not initiation. Amino acid analogues were
      inactive, as were the metabolic inhibitors thiourea, 2,4-dinitrophenol and
      fluoride. The compounds which inhibited the formation of perithecia also lowered
      the branching frequency of leading hyphae, but not their linear growth rates.
      Consequently, the branch densities were diminished in their presence. Hypotheses
      to account for these findings are discussed in terms of inhibition of growth in
      general, of the synthesis of some specific messenger RNAs, and of RNA-mediated
      transport across membranes, the last of which seeming the most fruitful for
      further work.

PMID- 16656615
TI  - Relationships Between Seed Respiration During Imbibition and Subsequent Seedling
      Growth in Zea mays L.
AB  - Corn (Zea mays L.) seed respiration rates during the first 30 hours of
      germination were compared with seedling growth 3 to 5 days after planting.
      Significant positive correlations were observed between rates of O(2) uptake
      during imbibition and later stages of germination and seedling growth. Glutamic
      acid decarboxylase activity also was positively correlated with seedling growth.
      The highly significant correlations between respiratory quotients and seedling
      growth were negative.Seed metabolism during the initial hours of germination is
      evidently related somehow to seedling growth rates several days later. Whether
      this relationship is due to the dependence of synthetic processes and growth on
      respiratory energy, the fact that high respiration rates reflect high levels of
      metabolic activity, or to some other cause, remains to be determined.

PMID- 16656616
TI  - An effect of light on the production of ethylene and the growth of the plumular
      portion of etiolated pea seedlings.
AB  - The production of ethylene by etiolated pea epicotyls (Pisum sativum L., cv.
      Alaska) is confined to the plumule and plumular hook portion of the epicotyl, and
      occurs at a rate of about 6 mul.kg(-1).hr(-1). Such a rate is sufficient to give
      physiologically active concentrations of ethylene within the tissue. Exposure of
      etiolated seedlings to a single dose of red light caused a transient decrease in
      ethylene production and a corresponding increase in plumular expansion. Far-red
      irradiation following the red light treatment decreased the red effect to the
      level achieved by the far-red alone, suggesting that the ethylene production
      mechanism is controlled by phytochrome and thus that the ethylene intervenes as a
      regulator in the phytochrome control of plumular expansion.

PMID- 16656617
TI  - Changes in the pattern of protein synthesis induced by 3-indolylacetic Acid.
AB  - Experiments have been performed to investigate whether indoleacetic acid changes
      the balance between the rates of synthesis of different kinds of proteins. Sub
      apical sections of etiolated peas were incubated with (14)C- or (3)H-labeled
      amino acid, and combined to give dual-labeled tissue. Cell fractions were
      prepared by differential centrifugation, and the dual-labeled protein of each
      fraction analyzed by gel-filtration. When 2 x 10(-5)m indoleacetic acid was
      included with (14)C-labeled amino acid, but not with the (3)H-labeled amino acid,
      pronounced changes occurred in the pattern of incorporation of the (14)C label
      into protein. These changes were greatest in the proteins of the particulate
      fraction which included nuclear material. Although the pattern of incorporation
      of lysine was shown to be different from that of leucine, the changes induced by
      indoleacetic acid were quantitatively similar whichever amino acid was used as a
      precursor. Dual-labeled protein was further fractionated using column
      chromatography on DEAE-cellulose. The results suggested that the effect of
      indoleacetic acid may not be completely general, and that the pattern of
      synthesis of many proteins may be unaltered by indoleacetic acid. When tissue was
      preincubated with 10 mug/ml actinomycin D for 30 minutes, incorporation of amino
      acid into protein was reduced but not abolished. Actinomycin D did, however,
      prevent the changes in the pattern of protein synthesis which were induced by
      indoleacetic acid.

PMID- 16656618
TI  - Phytochrome controlled C-sucrose uptake into etiolated pea buds: effects of
      gibberellic Acid and other substances.
AB  - The previously reported red light enhancement of (14)C-sucrose uptake into
      etiolated pea buds is inhibited by gibberellic acid applied no later than 2 hours
      after the light. Auxins, cytokinins and inhibitors of gibberellin biosynthesis
      are without effect, either alone or in the presence of gibberellic acid.

PMID- 16656619
TI  - Conversion of indole-3-ethanol to indole-3-acetic Acid in cucumber seedling
      shoots.
AB  - Indoleethanol-(14)C was applied to intact cucumber seedlings and to hypocotyl
      segments. The presence of indoleacetic acid-(14)C in tissue extracts was
      demonstrated by thin layer radiochromatography. There was no evidence of
      conversion of indoleacetic acid to indoleethanol. It is suggested that the growth
      promoting activity of indoleethanol is due to its conversion to indoleacetic
      acid.

PMID- 16656620
TI  - Abscission: the role of RNA synthesis.
AB  - Ethylene stimulated the incorporation of (32)P into RNA in the abscission zone of
      bean explants (Phaseolus vulgaris L. var. Red Kidney). The enhancement was
      observed in all fractions separated by methylated albumin kieselguhr column
      chromatography, although the magnitude of the increase was not the same for each
      fraction. Differential extraction of the nucleic acids indicated that the
      ethylene stimulation was confined to the fraction extracted with sodium lauryl
      sulfate, with the increase mainly in Fraction III (Ribosomal RNA) and Fraction IV
      (Messenger RNA). Actinomycin D, which blocks ethylene-stimulated abscission,
      inhibited (32)P incorporation into all column fractions. 5-Fluorouracil, which
      blocked 50% of the ethylene-enhanced (32)P incorporation, did not inhibit
      ethylene-enhanced abscission. The results indicate that ethylene may regulate
      abscission through control of specific RNA's.

PMID- 16656621
TI  - Cytochemical demonstration of a sodium-activated and a potassium-activated
      adenosine triphosphatase in loblolly pine seedling root tips.
AB  - Sodium stimulated ATPase activity in the nuclei of the meristematic cells, while
      potassium stimulated it in the mycorrhizae between root cap cells. The detection
      of these 2 mutually exclusive cation-stimulated ATPases, which both require
      magnesium-ATP in equivalents, which have a similar optimum pH of about 5.5, and
      which are located in entirely different parts of the root tip, suggests that
      particular enzyme systems can only be activated by a specific cation and that one
      cation cannot substitute for the other. Such a feature may explain the capacity
      of plants to differentiate between ions as closely similar as sodium and
      potassium. The similarities between the enzyme system described for salt
      transport in animal tissues and that depicted here cytochemically in pine roots
      at the most active site of salt uptake in roots indicate this may be a carrier
      mechanism for salt entry into plant roots. The presence of the potassium
      activated enzyme only in the mycorrhizae may relate to the dependence of pine
      trees on mycorrhizae for growth.

PMID- 16656622
TI  - Geotropic Response of Coleoptiles under Anaerobic Conditions.
AB  - Coleoptiles of Avena sativa and Zea mays do not develop a geotropic response
      under anaerobic conditions.

PMID- 16656623
TI  - Massive synthesis of ribonucleic Acid and cellulase in the pea epicotyl in
      response to indoleacetic Acid, with and without concurrent cell division.
AB  - Measurements were made over a 4-day period of the effect of added indoleacetic
      acid (IAA), puromycin, actinomycin D and 5-fluorodeoxyuridine (FUdR) on growth
      and the levels of total DNA, RNA, protein and cellulase in segments of tissue at
      the apex of decapitated etiolated epicotyls of Pisum sativum, L. var. Alaska.The
      hormone induced swelling of parenchyma cells and cell division. By 3 days after
      IAA application, the amounts of DNA and protein were approximately double, RNA
      triple and cellulase 12 to 16 times the levels in controls. All of these changes
      were prevented by both puromycin and actinomycin D. FUdR prevented DNA synthesis
      and cell division but not swelling or synthesis of RNA, protein and cellulase.It
      is concluded that IAA-induced RNA synthesis is required for cellulase synthesis
      and lateral cell expansion, whether or not cell division takes place.

PMID- 16656624
TI  - Changes in Chlorophyll a/b Ratio and Products of CO(2) Fixation by Algae Grown in
      Blue or Red Light.
AB  - Chlamydomonas and Chlorella were grown for 10 days in white light. 955 muw/cm(2)
      blue light (400-500 mmu) or 685 muw/cm(2) red light (above 600 mmu). Rates of
      growth in blue or red light were initially slow, but increased over a period of 5
      days until normal growth rates were reestablished. During this adaptation period
      in blue light, total chlorophyll per volume of algae increased 20% while the
      chlorophyll a/b ratio decreased. In red light no change was observed in the total
      amount of chlorophyll or in the chlorophyll a/b ratio. After adaptation to growth
      in blue light and upon exposure to (14)CO(2) with either blue or white light for
      3 to 10 minutes, 30 to 36% of the total soluble fixed (14)C accumulated in
      glycolate-(14)C which was the major product. However, with 1 minute experiments,
      it was shown that phosphate esters of the photosynthetic carbon cycle were
      labeled before the glycolate. Glycolate accumulation by algae grown in blue light
      occurred even at low light intensity. After growth of the algae in red light,
      (14)C accumulated in malate, aspartate, glutamate and alanine, whereas glycolate
      contained less than 3% of the soluble (14)C fraction.

PMID- 16656625
TI  - Effect of Root Temperature on Cytokinin Activity in Root Exudate of Vitis
      vinifera L.
AB  - Root exudates of plants of Vitis vinifera L. cv. Thompson Seedless, grown in
      nutrient cultures with root temperatures maintained at either 20 degrees or 30
      degrees and with shoots at a common air temperature, were assayed for cytokinin
      activity. After chromatography of freeze-dried sap on paper with n-butanol/acetic
      acid/water (4:1:1). activity was detected with a soybean callus assay. For both
      root temperatures, major activity appeared between R(F) 0.6 and R(F) 0.8, at
      about the same concentration in each case. The major difference between the 2
      samples was the presence of activity at R(F) 0.1 to 0.2 in the 20 degrees sample
      and its absence in the 30 degrees sample.The higher root temperature resulted in
      increased shoot and root elongation, increased dry matter accumulation by both
      shoots and roots, and also altered the morphological appearance of the roots.

PMID- 16656626
TI  - Relationship between Protein Synthesis in Tuber Discs and the Protein Synthetic
      Activity of a Cell-Free Preparation.
AB  - A cell-free system which synthesizes protein was isolated from ;aged' discs of
      Jerusalem artichoke tubers. The synthetic activity was largely associated with
      the fraction containing mitochondria. Preparations from freshly cut tissue were
      virtually inactive but increasingly active preparations were obtained from discs
      ;aged' for progressively longer periods; those from 24 hour discs showing maximum
      activity. The characteristics of this change are reminiscent of the rate of
      development of invertase, a marker for protein synthesis in the intact disc.
      Extensive investigations showed that bacterial contamination was not a
      significant factor in the synthetic activity.

PMID- 16656627
TI  - Phytochrome and Seed Germination. II. Changes of Pfr Requirement for Germination
      in Tomato Seeds.

PMID- 16656628
TI  - Nature of a rapidly labeled RNA fraction described in higher plant systems.

PMID- 16656629
TI  - Photosynthetic assimilation of carbon dioxide and acetate by isolated
      chloroplasts.

PMID- 16656630
TI  - Four low-cost monochromatic sources of known equal intensities.

PMID- 16656631
TI  - Isolation and properties of the enzyme system forming indoleacetic Acid.

PMID- 16656632
TI  - Synthesis of Indoleacetic Acid via Tryptamine by a Cell-free System from Tobacco
      Terminal Buds.

PMID- 16656634
TI  - Inhibition of formation of protein-bound hydroxyproline by free hydroxyproline in
      Avena coleoptiles.
AB  - Free hydroxyproline inhibits the formation of protein-bound hydroxyproline from
      proline to a considerably greater extent than it does the incorporation of
      proline into protein of auxin-treated Avena coleoptiles. This inhibition is
      greater in the wall than in the cytoplasmic fraction. In the absence of auxin,
      free hydroxyproline exerts little or no inhibition of hydroxyproline formation.
      Furthermore free hydroxyproline has no effect on respiration, RNA synthesis or
      the incorporation of leucine into protein. Hydroxyproline is not a general
      inhibitor of metabolism or protein synthesis in Avena coleoptiles.These results
      suggest that free hydroxyproline may inhibit auxin-induced cell elongation by
      blocking the formation or utilization of a particular hydroxyproline-rich protein
      which must be incorporated into the cell wall during auxin-induced wall
      extension.

PMID- 16656635
TI  - Absorption and translocation of sodium in beans and cotton.
AB  - At the end of a 4 hour absorption period approximately 95% of the sodium absorbed
      by bean plants was retained in the secondary roots. The sodium translocated to
      the shoot was retained in the stem.2,4-Dinitrophenol decreased the amount
      retained in the secondary roots of bean plants and increased the amount
      translocated to the shoot. The stem retained most of the translocated sodium.Bean
      plants without roots absorbed considerably more sodium than plants with roots and
      translocated a greater proportion of the sodium to the petioles and blades. 2,4
      Dinitrophenol reduced the amount of sodium in the stem and petioles and increased
      the amount in the blades.2,4-Dinitrophenol reduced the amount of sodium retained
      by the secondary roots of cotton plants but did not appreciably affect the
      amounts translocated to the shoot.

PMID- 16656636
TI  - Ribonuclease activity of stressed tomato leaflets.
AB  - Homogenates of leaflets of desiccated tomato plants show increased ribonuclease
      activity compared to homogenates of turgid controls. Much of this increase is
      independent of changes in translocation to and from the leaflet. Interruption of
      translocation through living cells by detachment of leaflets or steam damage to
      the petiolules produces increased ribonuclease activity, but this activity is
      increased further when excised leaflets are allowed to wilt. Increases in
      ribonuclease often parallel or precede increases in the soluble nitrogen content.
      Further increases in activity occur when excised leaves become yellow. Exposure
      of leaflets to CO(2)-free air has little effect on activity at low-light
      intensity (120 ft-c). These results suggest that water stress directly affected
      ribonuclease activity at the cellular level.

PMID- 16656637
TI  - In Vitro Protein Synthesis by Plastids of Phaseolus vulgaris. I. Localization of
      Activity in the Chloroplasts of a Chloroplast Containing Fraction from Developing
      Leaves.
AB  - The incorporation of uniformly labeled leucine-(14)C into protein by a
      chloroplast containing fraction from developing primary leaves of bean is
      reported. Chloroplasts, obtained from week old plants grown in darkness, and then
      illuminated with white light for 12 hours, were shown to be the principal sites
      of incorporating activity. Incorporation may continue for 2 hours. Rates of up to
      50 mumumole leucine incorporated per mg protein per hour are observed when a 1
      hour assay period is used. Incorporation is only partially sensitive to
      ribonuclease.

PMID- 16656638
TI  - Effects of Metabolic Inhibitors on the Rates of CO(2) Evolution in Light and in
      Darkness by Detached Spruce Twigs, Wheat, and Soybean Leaves.
AB  - Detached spruce twigs, wheat and soybean leaves were infiltrated with various
      metabolic inhibitors, placed in a closed system in CO(2)-free air and the amounts
      of CO(2) evolved in either light or darkness were determined with an infra-red
      CO(2) analyzer. In light, metabolic inhibitors always greatly suppressed
      evolution of CO(2), the magnitude of suppression varying between 50 to 80% of
      that without an inhibitor. This depressing effect became less pronounced with
      increasing oxygen. In darkness, metabolic inhibitors sometimes suppressed and
      sometimes stimulated CO(2) evolution. These observations have been taken as
      further support for a conclusion made earlier, that evolution of CO(2) in light
      and darkness is not the same process.

PMID- 16656639
TI  - Environmental control of cold hardiness in woody plants.
AB  - The development of cold hardiness in 2 woody plant species (Acer negundo and
      Viburnum plicatum tomentosum) was shown to be independent of the induction of bud
      dormancy. Substantial hardiness levels were obtained under controlled conditions
      with long days and certain low temperatures-without dormancy development as a
      prerequisite.Low temperatures given during the dark period with long days induced
      hardiness to a level not significantly different from that of short days. Giving
      plants continuous 10 degrees temperatures under long days forced plants to harden
      as if they were under short days, even though they were not dormant.Development
      of hardiness was shown to be a photoperiodic response. Increasing weeks of short
      days, followed by a low temperature hardening period in darkness, brought about a
      progressive increase in hardiness. The short day stimulus could be reversed by
      long days. Following 6 weeks of short days, the rate of hardening in darkness at
      5 degrees was over twice that of plants previously exposed to long days.

PMID- 16656640
TI  - Compartmentation of Organic Acids in Corn Roots. III. Utilization of Exogenously
      Supplied Acids.
AB  - The rates of utilization of exogenously supplied (14)C labeled acids by corn
      roots was compared to the utilization of these acids generated endogenously in
      the mitochondria from acetate-(3)H. (14)C-labeled citrate, pyruvate, succinate,
      glutamate or aspartate were supplied with acetate-(3)H in a 15 minute pulse and
      the (14)C and (3)H contents of extracted acids were measured over a 4 hour
      period. It was found, in contrast to previous experiments with malate, that these
      exogenously added acids were used as rapidly as the endogenous forms. Apparently,
      therefore, these acids penetrate readily into the mitochondria and do not enter
      cytoplasmic pools which are not in ready equilibrium with those in the
      mitochondria. Small amounts of labeled glutamate were produced from succinate-2,3
      (3)H by corn root tissue. Since glutamate would not be expected to be labeled by
      reactions of the tricarboxylic acid cycle it was concluded that it was produced
      rather directly from succinate. The minor pool of glutamate generated in this way
      retained its radioactivity while that generated in the cycle was rapidly lost. An
      extra-mitochondrial location of this pool of glutamate is therefore suggested.

PMID- 16656641
TI  - Sodium and rubidium as possible nutrients for sugar beet plants.
AB  - This study concerned the degree to which Na or Rb could substitute for K in the
      growth of sugar beet plants when K in the culture solution was low (1 meq/liter)
      or high (12 meq/liter).Sodium at high concentrations increased the growth of
      plants in a basal nutrient medium when either deficient in K or when adequately
      supplied with K alone. Redistribution of K from petioles to blades could not
      fully explain these results. Therefore, the essentiality of Na per se for growth
      of sugar beet plants may be inferred.Rubidium increased the growth of plants
      significantly when supplied in small doses to a nutrient medium deficient or
      adequately supplied with K. The amount of K added and the mode of Rb addition to
      solution cultures should be carefully considered when studying the effect of Rb
      on growth. High Rb concentrations were toxic, especially to the growth of fibrous
      roots.Sodium or Rb have been shown to enhance the growth of sugar beet plants
      under either low or high K conditions. Essentiality of either Na and/or Rb per se
      for growth of sugar beets may be inferred, but other criteria should be fulfilled
      also for conclusive proof.

PMID- 16656642
TI  - Action of Plant Growth Regulators. IV. Adsorption of Unsubstituted and 2,6
      Dichloro-aromatic Acids to Oat Monolayers.
AB  - The adsorption of chloro-aromatic acids to monomolecular layers of oat squashes
      is reported in earlier papers but it was not possible by the technique used, to
      measure unambiguously the adsorption of unsubstituted and 2,6-dichloro-aromatic
      acids. This has now been achieved by a modification of the earlier method and
      involves assessments of competitive adsorption between the unknown acid and a
      standard acid, using measurements of surface potential.Benzoic and phenoxyacetic
      acids were not adsorbed but phenylacetic acid was weakly adsorbed. The second
      ring in naphthalene and naphthoxyacetic acids greatly increased adsorption.
      Substitution of the 2 and 6 positions in the phenyl and phenoxyacetic acids
      resulted in low adsorption but 2,6-disubstituted phenoxybutyric and benzoic acids
      were more highly adsorbed.The adsorption values from earlier work are combined
      and discussed in relation to the growth-regulating activity of the acids. It is
      conciuded that there is no direct relation embracing all acids between adsorption
      and activity, notable exceptions being those substituted by chlorine in the 3
      position of the aromatic ring. However, for a number of acids it is suggested
      that activity is limited not only by their ability to interact at enzyme sites
      but also by the amount of acid immobilised by adsorption when moving to these
      sites. It is also concluded that the hydrophilic/lipophilic balance of a growth
      regulator sometimes used as a guide to its activity, is an unreliable indication
      of interfacial behaviour.

PMID- 16656643
TI  - Biosynthesis of Alkali Insoluble Polysaccharide from UDP-d-Glucose with
      Particulate Enzyme Preparations from Phaseolus aureus.
AB  - A particulate enzyme system from Phaseolus aureus seedlings catalyzes the
      synthesis of alkali insoluble polysaccharide material from UDP-d-glucose. 80 to
      90% of the d-glucose units are joined by beta-1,4 linkages, the remainder being
      combined by beta-1,3 linkages. It is not known whether the material is a single
      polysaccharide or a mixture.With a substrate concentration of 4 x 10(-3)m the
      enzyme system catalyzes the formation of alkali insoluble polysaccharide from UDP
      d-glucose at a rate 23 times greater than that from GDP-d-glucose. The
      modifications introduced also increase the formation of cellulose from GDP-d
      glucose to 3 times the rate previously reported.None of the glycosyl nucleotides
      containing bases other than guanine or uracil (adenine, cytosine, thymine) served
      as substrate for the production of alkali insoluble polysaccharide with this
      enzyme system. dUDP-d-glucose could also not serve as substrate.

PMID- 16656644
TI  - Structure and function of tomato leaf chloroplasts during ammonium toxicity.
AB  - Ammonium toxicity resulted in morphological modifications of tomato leaf
      chloroplasts. The chloroplasts, which are normally flattened around the
      protoplast periphery, became ellipsoidally rounded and dispersed through the
      protoplasm. The first apparent effect of plastid degradation was development of
      many vesicles from the fretwork. Later the grana lamellae swelled, and some
      disappeared. Eventually, distinct grana could not be detected.Ammonium
      accumulation, chlorophyll loss, and photosynthetic decrease occurred
      simultaneously. Initial changes in these processes preceded the detection of
      modifications of fine structure; however, each continued with further breakdown
      of the chloroplasts.

PMID- 16656645
TI  - Effect of Inversion on Growth and Movement of Indole-3-acetic Acid in
      Coleoptiles.
AB  - The effect of a 180 degrees displacement from the normal vertical orientation on
      longitudinal growth and on the acropetal and basipetal movement of (14)C-IAA was
      investigated in Avena sativa L. and Zea mays L. coleoptile sections. Inversion
      inhibits growth in intact sections (apex not removed) and in decapitated sections
      supplied apically with donor blocks containing auxin. Under aerobic conditions,
      inversion inhibits basipetal auxin movement and promotes acropetal auxin
      movement, whereas under anaerobic conditions, it does not influence the movement
      of auxin in either direction. Inversion retards the basipetal movement of the
      peak of a 30-minute pulse of auxin in corn.The inversion-induced inhibition of
      basipetal auxin movement is not explained by an effect of gravity on production,
      uptake, destruction, exit from sections, retention in tissue, or purely physical
      movement of auxin. It is concluded that inversion (a) inhibits basipetal
      transport, the component of auxin movement that is metabolically dependent, and
      as a result (b) inhibits growth and (c) promotes acropetal auxin movement.

PMID- 16656646
TI  - Comparative Studies on Plastoquinone II. Analysis for Plastoquinones A, B, C, and
      D.
AB  - Two different methods for the extraction and assay of plastoquinones A, B, C and
      D from chloroplasts of green plants have been described. The long procedure
      involves separation of aqueous and lipid phases of extract in a separatory
      funnel, column chromatography, purification on thin-layer plates, and
      spectrophotometric assays for quantitative determination of the various
      plastoquinones. The short procedure is based on spotting lipid extracts from
      chloroplasts on thin layer plates and comparing leucomethylene blue spots of
      unknown quinones with a series of spots produced by known amounts of the 4
      standard plastoquinones on the same plate.Reliability of the 2 procedures is
      shown by presenting recovery data (82% recovery for PQ A by the long method and
      64-100% recovery by the short method). Various solvent systems for quinone
      purification are described. Separation of plastoquinones B and C into 6
      components each is demonstrated for spinach and a tomato mutant, high pigment
      (hp). Plastoquinone C is shown to be equivalent to C(1)-C(4) while D corresponds
      to PQ C(5) and C(6) according to Griffiths, Wallwork and Pennock's designation.
      The term PQ D is therefore redundant and should be abandoned in favor of specific
      designation of PQ C type.

PMID- 16656647
TI  - Comparative Studies on Plastoquinones. III. Distribution of Plastoquinones in
      Higher Plants.
AB  - The distribution of plastoquinones A 45, B and C was studied in representatives
      from 34 different plant families beginning with liverworts and mosses to higher
      plants. All of these species, including many monocots and dicots, contained
      significant amounts of the 3 quinones. Two species of Aesculus contained
      plastoquinone A 20 in addition to plastoquinone A 45, B, and C. Many dicots, such
      as Aesculus, watermelon, tobacco and tomato accumulated increasing quantities of
      plastoquinones A and C(1)-C(4) during the growing season. The concentrations of
      plastoquinones B and C(5)-C(6) tended to remain at a constant low level during
      the season (<0.01 mumole per mg chlorophyll). Preliminary studies with bean
      plants (Vicia faba and Phaseolus sp.) indicate that the levels of quinones varied
      little under different growth conditions (day length and temp.) although Vicia
      faba tended to have higher PQ A values with increased temperature.

PMID- 16656648
TI  - Atrazine metabolism and herbicidal selectivity.
AB  - Metabolism of the herbicide 2-chloro-4-ethylamino-6-isopropylamino-s-triazine
      (atrazine) was investigated in resistant corn (Zea mays L.) and sorghum (Sorghum
      vulgare Pers.), intermediately susceptible pea (Pisum sativum L.), and highly
      susceptible wheat (Triticum vulgare Vill.) and soybean (Glycine max Merril.).
      This study revealed that 2 possible pathways for atrazine metabolism exist in
      higher plants. All species studied were able to metabolize atrazine initially by
      N-dealkylation of either of the 2 substituted alkylamine groups. Corn and wheat,
      which contain benzoxazinone, also metabolized atrazine initially by hydrolysis in
      the 2-position of the s-triazine ring to form hydroxyatrazine. Subsequent
      metabolism by both pathways resulted in the conversion of the parent atrazine to
      more polar compounds and eventually into methanol-insoluble plant residue. No
      evidence for s-triazine ring cleavage was obtained.Both pathways for atrazine
      metabolism appear to detoxify atrazine. The hydroxylation pathway results in a
      direct conversion of a highly phytotoxic compound to a completely non-phytotoxic
      derivative. The dealkylation pathway leads to detoxication through one or more
      partially detoxified, stable intermediates. Therefore, the rate and pathways of
      atrazine metabolism are important in determining the tolerance of plants to the
      herbicide. Both quantitative and qualitative differences in atrazine metabolism
      were detected between resistant, intermediately susceptible, and susceptible
      species. The ability of plants to metabolize atrazine by N-dealkylation and the
      influence of this pathway in determining tolerance of plants to atrazine are
      discussed.

PMID- 16656649
TI  - Evidence for in vivo Light-induced Synthesis of Ribulose-1,5-diP Carboxylase and
      Phosphoribulokinase in Greening Barley Leaves.
AB  - WHEN ACTINOMYCIN D, PUROMYCIN, STREPTOMYCIN, CHLORAMPHENICOL, AND CYCLOHEXIMIDE,
      KNOWN INHIBITORS OF PROTEIN SYNTHESIS, WERE APPLIED TO LEAVES OF INTACT SEEDLINGS
      OR DETACHED LEAVES OF BARLEY PRIOR TO THEIR GREENING, THE SAME GENERAL RESPONSE
      RESULTED: the light-induced increase in activity of ribulose 1,5-diphosphate
      carboxylase was prevented while that of phosphoribulokinase was only partially
      suppressed; synthesis of chlorophyll was arrested. This is taken as preliminary
      evidence that de novo synthesis of protein may be responsible for the observed
      increase in ribulose-1,5-diphosphate carboxylase activity during greening.
      However, other factors may be involved with the light-induced stimulation of
      phosphoribulokinase.Carbohydrate metabolites and substrates of the enzymes failed
      to induce the formation of ribulose-1,5-diphosphate carboxylase and
      phosphoribulokinase in the dark. No evidence was found for the presence of
      inhibitors in etiolated seedlings or activators in illuminated leaves of barley.
      Carboxylase activity almost equal to that of the illuminated water control was
      stimulated by MgCl(2) in the dark; MgCl(2) had no effect on the activity of the
      kinase.

PMID- 16656650
TI  - Detecting mutants that have impaired photosynthesis by their increased level of
      fluorescence.
AB  - A technique is described for detecting mutants of Chlamydomonas reinhardi that
      have impaired photosynthesis. It is based on the fact that when photosynthetic
      electron transport is blocked there may be an increase in the level of
      fluorescence similar to that obtained in the presence of an inhibitor of
      photosynthetic electron transport such as dichlorophenyldimethylurea.

PMID- 16656651
TI  - Physiological effects of gibberellic Acid. X. The release of gibberellin-like
      substances by germinating barley embryos.
AB  - Barley embryos, completely free from endosperm, were excised from germinating
      grain at various times and allowed to diffuse into an aqueous medium for varying
      lengths of time. At the end of this time, the embryos and ambient solutions were
      separately extracted. Gibberellin-like activity in the extracts was determined
      with the barley endosperm bioassay using seed from the same variety, harvest and
      treatment schedule as was employed for the embryo diffusion experiments.
      Gibberellin-like substances were released by embryos throughout the 60 hour
      germination period, though at no time during this period could sufficient
      activity be extracted from the embryos themselves to account for the observed
      release. Solvent partitioning and chromatography identified at least one major
      acidic component migrating at an Rf similar to that of GA(3).It is concluded that
      the endogenous gibberellin-like substance(s) originates within the embryo during
      germination, and that the release of this substance(s) is temporally consistent
      with, and quantitatively sufficient to account for the in vivo endosperm
      mobilization response syndrome. A gibberellin-like substance is undoubtedly the
      endosperm mobilizing hormone.

PMID- 16656652
TI  - Activation of protein synthesis by microsomes from aging beet disks.
AB  - Microsomal fractions isolated from sterile, aged disks of red beetroot
      incorporate leucine into protein when supplemented with the supernatant fraction,
      ATP, GTP, and KCl; the incorporation is sensitive to RNase and is not due to
      bacteria. The microsomal activity is inhibited by puromycin and cycloheximide but
      is virtually insensitive to both d-threo and l-threo-chloramphenicol, as
      predicted from physiological studies.Microsomes isolated from fresh disks have
      much lower incorporating ability than those from disks aged for 1 or 2 days;
      maximal activity occurs when the rate of protein synthesis by the intact disks is
      highest. The low activity of fractions from fresh disks is attributable to a
      deficiency in the microsomal fraction and not to the supernatant fraction; it is
      not due to a dissociable inhibitor. The RNA content of the microsomal fraction
      increases with aging and so the increase in incorporating ability may be due to a
      synthesis of messenger RNA induced by slicing, rather than to an activation of
      pre-existing messenger. These results support the view that the aging phenomenon
      involves a derepression of gene activity.

PMID- 16656653
TI  - Light-induced inhibition of tryptophan decarboxylation in cell-free extracts of
      pea epicotyls.

PMID- 16656654
TI  - Effect of Selected Nitrogen-bases and Boron on the Ribonucleic Acid Content,
      Elongation, and Visible Deficiency Symptoms of Tomato Root Tips.

PMID- 16656655
TI  - Photoreduction sites for 2,6-dichlorophenolindophenol in chloroplasts.

PMID- 16656657
TI  - Comparison of the dye method with the thermocouple psychrometer for measuring
      leaf water potentials.
AB  - The dye method for measuring water potential was examined and compared with the
      thermocouple psychrometer method in order to evaluate its usefulness for
      measuring leaf water potentials of forest trees and common laboratory plants.
      Psychrometer measurements are assumed to represent the true leaf water
      potentials. Because of the contamination of test solutions by cell sap and leaf
      surface residues, dye method values of most species varied about 1 to 5 bars from
      psychrometer values over the leaf water potential range of 0 to -30 bars. The dye
      method is useful for measuring changes and relative values in leaf potential.
      Because of species differences in the relationships of dye method values to true
      leaf water potentials, dye method values should be interpreted with caution when
      comparing different species or the same species growing in widely different
      environments. Despite its limitations the dye method has a usefulness to many
      workers because it is simple, requires no elaborate equipment, and can be used in
      both the laboratory and field.

PMID- 16656658
TI  - Chloroplast Integrity and ATP-Dependent CO(2) Fixation in Spinacia oleracea.
AB  - Washed whole chloroplasts of Spinacia oleracea isolated and assayed in a tris
      (hydroxymethyl aminomethane)-HCl buffered sucrose solution exhibited low dark
      CO(2) fixing activity, whereas washed whole chloroplasts isolated in the same
      buffer but assayed in that buffer without sucrose exhibited much greater dark
      CO(2) fixing activity. The lowered activity could be attributed to the
      impermeability of the chloroplast membrane to ribose-5-phosphate or adenosine
      triphosphate. The preservation of the integrity of the chloroplast membrane, as
      reflected by its impermeability to either or both of the abovementioned
      compounds, was measured by the fixation of (14)CO(2) into acid-stable products in
      the presence of ribose-5-phosphate and adenosine triphosphate by the whole
      chloroplast as compared with fixation by the chloroplast extract. An effect
      (i.e., apparent resistance to the passage of ribose-5-phosphate or adenosine-5
      triphosphate into the chloroplast) similar to, but less pronounced than, that
      produced by the presence of sucrose in the isolation medium was observed upon the
      addition of MnCl(2) or CaCl(2) to the buffered sucrose isolation medium. The
      addition of KCl enhanced slightly the effect produced by addition of sucrose
      alone to the isolation medium. The presence of MgCl(2) in the isolation medium,
      however, either caused the chloroplasts to become leaky or more fragile since
      more of the activity of the carboxylative phase enzymes appeared in the
      cytoplasm. When a mixture of all of the metal ions was added to the buffered
      sucrose suspending medium, the chloroplasts exhibited the same response observed
      with MgCl(2) alone. The addition of ethylene diaminetetraacetate or
      dithiothreitol appeared to alter the permeability of the chloroplast membrane
      nonspecifically when the assay was conducted in the absence of sucrose. Specific
      activities (mumoles CO(2) fixed/mg chlorophyll x hr) as high as 329.6 have been
      observed for dark fixation by chloroplasts. The phosphoenolpyruvate carboxylase
      activity in the chloroplasts was only one-seventh that of ribulose diphosphate
      carboxylase. The phosphoenolpyruvate carboxylase activity in the cytoplasm was 5
      times that of the chloroplasts.

PMID- 16656659
TI  - Auxin-gibberellin interaction in apical dominance.
AB  - Indoleacetic acid and gibberellic acid were added to decapitated light-grown
      ;Alaska' pea seedlings as substitutes for the intact apex in the control of
      apical dominance. Of various concentrations and combinations tried, a combination
      of 1% indoleacetic acid + 1% gibberellic acid was the most inhibiting to side bud
      growth. The greatest degree of hormonally induced side bud inhibition was
      achieved when seedlings were deprived of soil nutrients.

PMID- 16656660
TI  - Senescence: action of auxin and kinetin in control of RNA and protein synthesis
      in subcellular fractions of bean endocarp.
AB  - A comparative study was made of the effects of auxin (alpha-naphthalene acetic
      acid), kinetin (6-furfurylaminopurine) and a mixture of auxin and kinetin applied
      in vivo on synthesis of RNA and protein and the distribution of such synthesis
      amongst the subcellular fractions of sections of endocarp from Kentucky Wonder
      pole beans (Phaseolus vulgaris, L.). Auxin caused considerable enhancement of
      incorporation of labeled precursors into RNA and protein of all subcellular
      fractions, and induced net synthesis of RNA and protein. That auxin-induced net
      synthesis of protein is repressed by actinomycin D indicates that auxin acts
      primarily to stimulate synthesis of RNA, as a result of which synthesis of
      protein is enhanced. The effect of kinetin alone on synthesis of RNA, or of
      kinetin on auxin-induced synthesis of RNA was variable, with either stimulation
      or inhibition observed in different experiments. Kinetin-enhancement of synthesis
      of both RNA and protein in subcellular fractions also varied, with enhancement of
      synthesis in 1 or all subcellular fractions among different experiments. The
      variable effect of kinetin did not seem to be related to the amount of endogenous
      or added auxin. The mode of action of kinetin is discussed.

PMID- 16656661
TI  - Freezing injury and uncoupling of phosphorylation from electron transport in
      chloroplasts.
AB  - Freezing of chloroplast membranes uncouples photophosphorylation from electron
      transport and inactivates the light-dependent and thiol-requiring ATPase,
      conformational changes and the light-dependent proton uptake. All of these energy
      requiring activities can be protected against inactivation by addition of sucrose
      prior to freezing. The direct relation to photophosphorylation is demonstrated by
      the quantitatively similar response of photophosphorylation and the other
      activities to sucrose protection. Salts interfere with the protection afforded by
      sucrose.In contrast to the light-dependent ATPase, the ATPase activities which
      are unmasked by digestion with trypsin show no significant response to freezing.
      Similarly, the chloroplast coupling factor, which is released from the membranes
      by ethylenediamine tetraacetic acid treatment, survives freezing. The membranes,
      which are depleted of the factor, are damaged by freezing.The results suggest
      that uncoupling of phosphorylation from electron transport is caused by
      interference of freezing with a structure involved in the formation of a non
      phosphorylated high energy state of chloroplasts. They are best explained on the
      basis of Mitchell's theory of phosphorylation. Since freezing alters the
      permeability properties of chloroplast membranes-frozen membrane vesicles no
      longer function as osmometers-it may be assumed that freezing uncouples
      phosphorylation from electron transport by preventing the formation of a pH
      gradient across the vesicle membranes owing to proton leakage through the
      membranes. From the results, the basic injury caused by freezing appears to
      consist in the alteration of permeability properties of biological membranes due
      to the dehydration which accompanies freezing.

PMID- 16656662
TI  - Abscission: the role of aging.
AB  - Excision of Phaseolus vulgaris L. c.v. Red Kidney abscission zone explants
      results in senescence, mobilization, and abscission. Because these processes take
      place at about the same time, there has been some question as to whether they are
      causally related or are occurring in an independent but simultaneous fashion.
      Data presented here suggest that the latter interpretation is correct. After
      abscission zone explants are isolated from the leaf an aging process is set into
      motion and a degradation of metabolites in the pulvinus takes place. During the
      aging process the explants also become increasingly sensitive to ethylene which
      in turn promotes cell separation. Indoleacetic acid, cytokinins, and coumarin
      appear to retard aging since both degradative processes and abscission are
      inhibited. However, ethylene increased abscission without increasing degradative
      processes indicating that abscission and senescence are independent processes
      occurring at the same time.

PMID- 16656663
TI  - Phosphorylation in avocado fruit slices in relation to the respiratory
      climacteric.
AB  - The rate of uptake of inorganic phosphate by tissue discs from both
      preclimacteric and climacteric peak avocados is linear for at least 60 minutes.
      The loss of (32)P upon excessive washing was much greater from peak than from
      preclimacteric tissue. Short incubation periods and, most important, rapid
      washing procedures are essential for meaningful comparisons.Phosphate
      esterification proceeded at a much greater rate in climacteric than in
      preclimacteric tissue. The phosphorylation was sensitive to 2,4-dinitrophenol
      (DNP). The ADP to ATP ratio decreased materially with the advance of ripening. It
      was concluded that neither uncoupling nor acceptor control can account for the
      onset of the respiratory rise. Changes in permeability appear to play an
      important role in fruit metabolism during the climacteric.

PMID- 16656664
TI  - Translocation of Indole-3-acetic Acid-1'-C and Tryptophan-1-C in Seedlings of
      Phaseolus coccineus L. and Zea mays L.
AB  - Indole-3-acetic acid-1'-(14)C (IAA-(14)C) and tryptophan-1-(14)C injected in
      small amounts into cotyledons of Phaseolus coccineus L. seedlings were found to
      be translocated acropetally into the epicotyls and young shoots. Similarly IAA
      (14)C was translocated acropetally into coleoptiles of Zea mays following
      injection into the endosperms. Labeled metabolites of the injected compounds were
      also extractable from shoot tissue. However, evidence that IAA-(14)C itself was
      translocated acropetally was obtained by collection in agar blocks applied to cut
      surfaces of coleoptiles of injected seedlings. The acropetal translocation in
      Phaseolus was shown not to occur in the transpiration stream but in living
      tissue. Cotyledons of Phaseolus coccineus and Phaseolus vulgaris contain
      extensive vascular tissue.Tryptophan-(14)C was not actively translocated through
      excised segments of Phaseolus coccineus epicotyl and Zea mays coleoptile when
      supplied from donor agar blocks in concentrations as high as 100 mum. The small
      amount of tryptophan-(14)C which did reach receiver blocks when high
      concentrations were used may be accounted for by passive diffusion through the
      fluid-filled xylem vessels. Translocation of a non-toxic dye, Light Green SF
      Yellowish, through xylem vessels was found to occur when supplied from donor
      blocks placed acropetally or basipetally. Metabolism of the supplied tryptophan
      (14)C by the tissue segments was shown to occur during the 3 to 6 hour
      translocation experiments. IAA-(14)C was transported in a strictly basipetal
      manner in both tissues. Only 1 labeled compound with an R(F) value of IAA was
      found in receiver blocks. Composition of a simple green safelight suitable for
      work in plant physiology is described.

PMID- 16656665
TI  - Causal basis of gravity stimulus nullification by clinostat rotation.
AB  - Using appropriate clinostat rotation methods, it has been shown that increases in
      root growth and geotropic curvature of oat coleoptiles are related to and
      explained (within the limits of auxin economy) by increased rates of plant
      respiration imparted by nullification of the gravitational stimulus. Increased
      respiration with decreased gravitational stimulus, in turn, is explained by
      increased uniformity in intracellular distribution of metabolically active
      graviprecipitable particles.Oat seedlings grown with nullification of the
      gravitational stimulus show a more uniform distribution of graviprecipitable
      protoplasmic inclusions. Respiration involves reactions between particles of
      sufficient mass to be precipitated in 1 x g unidirectional force field and
      particles of such size that they are distributed throughout the protoplasm due to
      thermal energy. When plants are grown without nullification of the gravitational
      stimulus, graviprecipitable protoplasmic inclusions tend to accumulate in the
      lower portions of the cells. Respiration rates are consequently limited due to a
      relatively low concentration of the smaller particles in the region of high
      concentration of the larger particles. Distribution of the larger particles
      throughout the protoplasm negates the reaction rate limiting effects of these
      intracellular concentration gradients.It has been shown using starch particles to
      index graviprecipitation of intracellular particles that enhancement of
      respiration by nullification of the gravitational stimulus may be induced,
      maintained, discontinued, and reinduced by treatments which concomitantly result
      in the more uniform distribution of graviprecipitable protoplasmic inclusions,
      the maintenance of this uniform distribution, the discontinuation of this uniform
      distribution and its reinduction.The degree of uniformity of intracellular
      particle distribution in response to treatments only partially nullifying the
      gravitational stimulus is shown wholly consonant with growth responses of roots
      and coleoptiles when the growth is measured as the expression of increased
      respiration in the absence of auxin limitation.The findings collectively indicate
      that gravity sensing by plants is broadly based on the physicochemical
      relationship between particle distribution and the expression of respiratory
      metabolism as growth.

PMID- 16656666
TI  - The long day leaf as a source of cold hardiness inhibitors.
AB  - Short photoperiods followed by low temperatures induced cold hardiness in Acer
      negundo, Viburnum plicatum tomentosum, and Weigela florida. Hardiness was also
      obtained under long days and natural fall temperatures if the leaves were
      removed, either manually or by low temperature. Similarly, removal of leaves from
      plants exposed to long days at 5 degrees brought about an accelerated rate of
      hardening. These observations suggested the presence of a hardiness inhibitor in
      the leaves which was counteracted by short days or removal of the leaves.

PMID- 16656667
TI  - A rapid technique for isolating chloroplasts with high rates of endogenous
      photophosphorylation.
AB  - THE MAIN FEATURES OF THE PROCEDURE DEVELOPED FOR RAPID CHLOROPLAST ISOLATION ARE:
      1) gentle grinding of the plant material in a special nylon bag which retains
      nearly all whole cells and large debris, 2) osmoticum concentration chosen on the
      basis of the measured endogenous photophosphorylation, 3) a single, brief, low
      speed centrifugation, 4) pellet resuspension by means of a vortex mixer, and 5) a
      total elapsed time from harvesting the plants to the obtaining of a resuspended
      chloroplast pellet of only 2 minutes. The usual isolation medium consists of an
      osmoticum (0.2 m sucrose) and a buffer (0.02 m N-tris-(hydroxymethyl) methyl-2
      aminoethanesulfonate-NaOH, pH 7.9). In addition to these, the incubation medium
      contains only 200 mum ADP and 200 mum phosphate. Photophosphorylation rates of 24
      mumoles ATP formed per mg chlorophyll per hour are consistently obtained using
      chloroplasts isolated from peas (Pisum sativum var. Laxton's Superb). The rate of
      endogenous photophosphorylation is maximal when the isolation and incubation
      media have an osmolarity of about 0.19 made up either with sucrose or with NaCl.
      The high rates and ease of measurement of endogenous photophosphorylation may
      facilitate the study of certain soluble components of chloroplasts as well as the
      general state of the photosynthetic ability of the plant.

PMID- 16656668
TI  - Studies on the oxidation of indole-3-acetic Acid by peroxidase enzymes. I.
      Colorimetric determination of indole-3-acetic Acid oxidation products.
AB  - The method described here is based on a brief report by Harley-Mason and Archer.
      It involves the use of p-dimethylaminocinnamaldehyde (DMACA), a vinylogue of
      Ehrlich's reagent, as a color reagent for indoles. Colorimetric analyses of
      indoleacetic acid (IAA) oxidation reaction mixtures were made with the DMACA
      reagent as a solution rather than a spray. DMACA reagent will yield a wine-red
      color with IAA oxidation products in solution. Under similar conditions DMACA
      reacts with authentic IAA to yield only slight coloration at best. In comparison
      with other indoles, DMACA is more relative with IAA oxidation reaction products
      than either Salkowski or Ehrlich's reagents. Data discussed support a concept
      that the color produced with DMACA is due to the presence of tautomeric oxidation
      product(s) of IAA.

PMID- 16656669
TI  - Properties of Higher Plant Mitochondria. II. Effects of DNP, m-Cl-CCP, and
      Oligomycin on Respiration of Mung Bean Mitochondria.
AB  - Effects of inhibitors of phosphorylation on the oxidation of succinate and of l
      malate were investigated with tightly coupled mitochondria isolated from mung
      bean hypocotyls. When mitochondria were incubated with 2,4-dinitrophenol, or
      carbonyl cyanide m-chlorophenylhydrazone prior to the addition of substrate, the
      uncoupling effects of these chemicals were relatively small. This is probably
      caused by relative lack in these mitochondria of endogenous substrates, ATP,
      and/or "high-energy intermediates". The action of uncoupling agents is,
      therefore, revealed in a more striking manner when they are introduced during the
      second state 4. Of the 2 uncoupling agents tested, malate oxidation consistently
      required 1.5 to 2 times higher concentration of the agents for the half-maximal
      effects than succinate oxidation. From the comparison of the degree of uncoupling
      it is concluded that 2,4-dinitrophenol is a better uncoupler of succinate
      oxidation, whereas carbonyl cyanide m-chlorophenylhydrazone functions as a more
      complete uncoupler of malate oxidation.Oligomycin does not inhibit state 4 rates,
      while the increment of respiration due to added ADP is completely inhibited by
      this antibiotic. Identical half-maximal effects are observed with the same
      concentration of oligomycin in both succinate and l-malate oxidation. The
      oligomycin effect depends on the mitochondrial concentration employed. The
      concentration of this chemical required for the half-maximal effect is 55 to 80
      mmumoles per mg mitochondrial protein. It is suggested that this inhibitor of
      phosphorylation binds all of the phosphorylation sites regardless of whether the
      sites are functional or not.

PMID- 16656670
TI  - Effects of temperature on orthophosphate absorption by excised corn roots.
AB  - The uptake of orthophosphate ((32)P) by excised corn roots, Zea mays L. was
      studied using roots grown on 0.2 mm CaSO(4). Nine concentrations of KH(2)PO(4)
      from 1 to 256 mum were used at temperatures of 20 degrees , 30 degrees , and 40
      degrees . Enzyme kinetic analysis was applied to the data obtained. Two apparent
      mechanisms (sites) of phosphate uptake were observed, 1 dominating at high P
      concentrations and 1 at low P concentrations. A Km of 1.36 x 10(-4) and a Vmax of
      177 x 10(-9) moles per gram of roots per hour at 30 degrees was calculated for
      the mechanism dominating at high P concentrations. Similar calculations gave a Km
      of 6.09 x 10(-6) and a Vmax of 162 x 10(-9) moles per gram of roots per hour at
      30 degrees for the mechanism dominating at low P concentrations. The Q(10) for
      both mechanisms was approximately 2. Calculation of thermodynamic values from the
      data gave DeltaF of - 5200 cal, DeltaH of - 950 to - 1400 cal, and a enthalpy of
      activation (A) of 10,300 to 13,800 cal per mole for the mechanism dominating at
      high P concentrations. Similar calculations from the data for the mechanism
      dominating at low P concentrations gave a DeltaF of - 7300 cal, DeltaH of -
      10,700 to - 8200 cal, and a A of 9300 to 18,900 cal per mole. If the dual
      mechanism interpretation of this kind of data adequately describes this system,
      then both mechanisms of P absorption by corn roots involve chemical reactions.

PMID- 16656671
TI  - Phytochrome Effects in the Nyctinastic Leaf Movements of Albizzia julibrissin and
      Some Other Legumes.
AB  - Participation of phytochrome is evident in the nyctinastic response of leaves of
      Albizzia julibrissin (silk-tree), Albizzia lophantha, Leucaena glauca, Poinciana
      gilliesi and Calliandra inequilatera; closure of excised pairs of pinnules upon
      darkening is rapid following red illumination and slow following far-red. Under
      good conditions the difference is obvious within 10 minutes. These observations
      confirm a report by Fondeville, Borthwick, and Hendricks on the sensitive plant,
      Mimosa pudica, but indicate that the effect bears no necessary relationship to
      the anomalous sensitivity of Mimosa. In A. julibrissin, phytochrome control is
      marked in experiments conducted early in the daily 12-hour light period and
      appears absent, or nearly so, toward the end of the light period, perhaps due to
      interaction with an endogenous circadian rhythm. Effects of leaf maturity and of
      the position of a pinnule-pair within a leaf are also evident.These results are
      not easily reconciled with hypotheses of phytochrome action through gene
      activation and nucleic acid synthesis, but are consistent with hypotheses based
      on permeability changes and membrane properties. The magnitude and
      reproducibility of the response in A. julibrissin suggest its use as a laboratory
      exercise; this and related systems should prove valuable for eventual
      identification of the mechanism of phytochrome action.

PMID- 16656672
TI  - Refinement of the triphenyl tetrazolium chloride method of determining cold
      injury.
AB  - The method of evaluating cold injury in woody plants by the use of triphenyl
      tetrazolium chloride has been refined to eliminate bias associated with visual
      differentiation between varying degrees of tetrazolium reduction and to predict
      tissue survival at a later date. An advantage of the method described here is
      that a small amount of tissue (50-100 mg) is required; this, therefore, allows
      for hardiness determinations at precise locations on the plant. The high
      correlation between cold injury and triphenyl tetrazolium chloride reduction may
      be due to cofactor and substrate limitations rather than inactivation of
      dehydrogenases.

PMID- 16656673
TI  - Translocation of manganese, iron, cobalt, and zinc in tomato.
AB  - Tomato plants in solution culture were treated with 0 to 50 mum Mn, Co, or Zn in
      the presence of 5 mum Fe. Stem exudates were analyzed to determine quantities and
      forms of the metals translocated.Mn had no effect on exudate volume. Co and Zn at
      5 mum and above depressed exudate volumes. Nutrient Mn was concentrated 2 to 5
      times in the exudates. Co and Zn concentrations were between 1 and 3.Tomato roots
      treated with 0 to 10 mum Mn released into the exudate an average of 29% of the Fe
      they absorbed. They released 21% of the absorbed Fe when treated with 50 mum Mn.
      On 50 mum Co or Zn, the roots released only about 1% of the absorbed Fe.The
      exudates contained 12 to 47 mum citrate, which was usually considerably in excess
      of Fe. Electrophoresis of exudate revealed Fe as the only metal in anionic form.
      Mn, Co, and Zn migrated as cations.The concentration of Ca was >3 mm and Mg >1.5
      mm in the exudates. Estimates based on metal-citrate equilibrium constants and
      constants of metal displacement caused by Ca and Mg confirmed that Mn, Co, and Zn
      were transported predominantly as inorganic cations in the stem exudates.

PMID- 16656674
TI  - Purification and Properties of a Phytotoxic Polysaccharide Produced by
      Corynebacterium sepedonicum.
AB  - A polysaccharide possessing a capacity to wilt plant cuttings has been isolated
      and purified from cultures of Corynebacterium sepedonicum. The molecular weight,
      based on the average of molecular weights determined by 3 physical methods, is
      21,450. The empirical formula of the polysaccharide is C(48)H(96)O(48)N. It is
      antigenic and the borate complex migrates in an electric field. It has an
      intrinsic viscosity of 0.125 and an S(20w) of 0.76. A hydrolysate of the compound
      yields glucose, mannose, 2 unidentified reducing compounds and 1 unidentified non
      reducing compound. The nitrogen in the toxin can be accounted for in 6 amino
      acids. Although the toxin is primarily polysaccharide it might more aptly be
      termed a glycopeptide.Some information regarding the physiological activity of
      this compound as well as a discussion of how it acts to bring about wilting is
      included.

PMID- 16656675
TI  - Preparation of Metabolically Active Protoplasts and Particle Preparations from
      the Blue-Green Alga, Phormidium luridum.
AB  - A method is described for the preparation of metabolically active protoplasts
      from the blue-green alga, Phormidium luridum. The isolated protoplasts are stable
      and are capable of endogenous respiration and photoassimilation of carbon dioxide
      at rates not appreciably different from the untreated filaments. The protoplasts
      can be ruptured by dilution of the stabilizing osmoticum and, therefore, they
      provide a convenient starting point for the production of cell-free preparations
      within a biochemical reaction mixture of interest.

PMID- 16656676
TI  - Photosynthetic Reactions by Lysed Protoplasts and Particle Preparations from the
      Blue-Green Alga, Phormidium luridum.
AB  - Reactions of photosynthetic electron transport and photophosphorylation were
      studied in preparations from the blue-green alga, Phormidium luridum. Osmotic
      lysis of protoplasts proved to be a superior technique for the production of cell
      free preparations with high enzymatic activity. Such lysed protoplasts sustain
      high rates of photophosphorylation coupled to the photo-reduction of NADP(+) or
      ferricyanide. P/2e(-) ratios close to unity were routinely observed. The same
      preparations, and also those prepared by grinding the cells in solutions
      containing sucrose or ethylene glycol, are active in cyclic photophosphorylation
      mediated by phenazine methosulfate or dichloro-phenolindophenol. The particles
      prepared by grinding the cells are, however, inactive in non-cyclic
      photophosphorylation.Extensive washing of the membranes with solutions containing
      sucrose removes the majority of the residual soluble fraction of the algal cell
      which includes cytochromes C(554) and C(549) and phycocyanin. Cyclic
      photophosphorylation activity is unimpaired by this treatment, but is abolished
      when the membranes are washed with very dilute buffers. This activity is restored
      by the addition of a soluble protein which is not a known redox constituent such
      as cytochrome C(554) or plastocyanin, and may be a coupling factor.Analysis of
      the well-washed membranes by low temperature (77 degrees K) difference
      spectrophotometry reveals the presence of cytochrome b(6) and a bound form of
      cytochrome C(554) in proportions similar to that found in higher plant
      chloroplasts. The concentration of the membrane-bound cytochrome C(554), relative
      to cytochrome b(6) is not altered by extensive washing, sonication or treatment
      with 1% digitonin. This indicates that this cytochrome is an integral component
      of the cytoplasmic lamellae and we suggest that it is of functional significance.
      The soluble form of cytochrome C(554), which is present in concentrations about 3
      fold higher than the bound form, depending upon growth conditions, is not
      essential for cyclic photophosphorylation. The concentration of cytochrome b(6):
      chlorophyll a was found to be 1:500.Under the conditions employed, we were unable
      to detect a bound form of the low potential cytochrome C(549).

PMID- 16656677
TI  - Sterols of Chlorella. II. The Occurrence of an Unusual Sterol Mixture in
      Chlorella vulgaris.

PMID- 16656678
TI  - Determination of infrared spectra on microgram quantities of some plant growth
      regulating compounds.

PMID- 16656679
TI  - High activity of the glycolic Acid oxidase system in tobacco leaves.

PMID- 16656680
TI  - The Expression of Interionic Relationships in Pinus elliottii.
AB  - The effects of factorial combinations of N, P and Mg on some of the
      interrelationships among nutrient ions as they occurred in seedlings of slash
      pine were investigated. In similar studies, true interactions have not always
      been differentiated from apparent interactions, the result of comparing foliage
      concentrations in plants with widely divergent growth rates. To prevent this,
      nutrient solutions were formulated to produce conditions ranging only from slight
      deficiency through luxury consumption. This relatively narrow range of nutrition
      allowed actual interactions to be separated from those changes in foliage
      concentration that are primarily a result of large differences in growth.The
      needles were analyzed for total and soluble N and total P, K, Ca, Mg and Na. Each
      level of each nutrient variable had a significant effect on the concentration of
      1 or more dissimilar elements. The familiar depressive effect of N on foliar P
      was observed; however this relationship was shown to be primarily the result of
      growth dilution rather than anion antagonism. Increased Mg did antagonistically
      reduce the uptake of Ca and, generally, K. Increments of P not required for
      growth stimulated uptake of N, Ca, Mg and K. No relationship was found between Mg
      supply and P accumulation.

PMID- 16656681
TI  - Relative Activities and Characteristics of Some Oxidative Respiratory Enzymes
      from Conidia of Verticillium albo-atrum.
AB  - Conidia of Verticillium albo-atrum Reinke and Berthold, collected from shake
      cultures grown in Czapek broth, were sonified for 4 or 8 minutes or ground frozen
      in a mortar to obtain cell-free homogenates. These were assayed for certain
      enzymes associated with respiratory pathways. Malic dehydrogenase was the most
      active, glucose-6-P and NADH dehydrogenase were less active, NADH-cytochrome c
      reductase, NADPH dehydrogenase, and cytochrome oxidase were low in activity, and
      succinic dehydrogenase and succinic cytochrome c reductase were very low to
      negligible in activity. No NADH oxidase activity was detected.With the exception
      of NADH-cytochrome c reductase and possibly succinic dehydrogenase and cytochrome
      c reductase, there was no evident increase in specific activity of the enzymes
      during germination. Some NADH-cytochrome c reductase and a small amount of
      succinic-dehydrogenase and cytochrome c reductase were associated with the
      particulate fraction from 105,000 x g centrifugation. The other enzymes,
      including cytochrome oxidase, almost completely remained in the supernatant
      fraction.Menadione and vitamin K-S(II) markedly stimulated NADH-cytochrome c
      reductase activity in the supernatant fraction but had much less effect on NADPH
      cytochrome c reductase in this fraction or on either of these enzyme systems in
      the particulate fraction. Electron transport inhibitors affected particulate NADH
      and NADPH-cytochrome c reductase activity but had no effect on these in the
      supernatant fraction.

PMID- 16656682
TI  - Phytochrome and Seed Germination. III. Action of Prolonged Far Red Irradiation on
      the Germination of Tomato and Cucumber Seeds.
AB  - Prolonged irradiation with continuous or intermittent far red prevents the
      germination of tomato and cucumber seeds. The inhibitory efficiency of
      intermittent far red decreases with the lengthening of the interval between
      successive irradiations, and with the increase of temperature. If each far red
      irradiation is followed by red, germination is restored. Intermittent far red is
      less inhibitory than intermittent red-far red when red is given immediately
      before each far red. This effect is more evident when the interval between
      successive irradiation becomes longer.

PMID- 16656683
TI  - Calcium inhibition of potassium absorption in corn roots.
AB  - Calcium (or magnesium) sulfate or chloride was found to inhibit energy dependent
      potassium transport in excised corn roots. This Ca(2+) inhibition of K(+)
      transport was most pronounced during the initial phases of transport. As the
      absorption periods were lengthened the effect of Ca(2+) gradually changed from an
      inhibition to a typical promotion (after about 30-45 mins) of K(+) transport.
      Kinetic analysis indicated the inhibition to be of a non-competitive
      nature.Identical experiments with excised barley roots showed that CaSO(4) had no
      effect on K(+) absorption whereas CaCl(2) had a typical stimulatory effect on
      K(+) absorption. Kinetic analysis indicated that both corn and barley have
      efficient K(+) transporting systems but barley roots are approximately 5 times
      more active (on a fr wt basis) than corn roots.These results illustrate the
      hazards involved in applying results obtained with 1 (or even several) plant
      species to all species.

PMID- 16656684
TI  - Effects of metabolic poisons on rice: the comparative sensitivity of aerobic and
      anaerobic modes of germination.
AB  - Rice germinates equally well when incubated in air and in nitrogen. It was
      therefore chosen for a comparative study of the effect of oxygen status in a
      single organism upon the activity of conventional metabolic poisons. Inhibitor
      activity was based upon the concentration required for 50% inhibition of
      germination. The inhibitors were: AgNO(3), HgCl(2), phenylmercuric acetate,
      iodoacetamide, KCN, NaN(3), NaF, fluoroacetate, 2,4-dinitrophenol, Na(2)HAsO(4)
      and CO. Only 5 inhibitors out of 11 differed significantly in their effects on
      aerobic and anaerobic germination. These included phenylmercuric acetate (N(2)),
      sodium fluoroacetate (air), NaN(3) (air), and 2,4-dinitrophenol (N(2)). CO
      activity was manifest only in air and it was photo-reversible. The effects of CO,
      NaN(3), and fluoroacetate were consistent with their conventional role in aerobic
      metabolism. The failure of KCN to discriminate was attributed to its relative non
      specificity. 2,4-Dinitrophenol behaved anomalously, requiring a 20-fold lower
      concentration for inhibition under nitrogen than under air. Among sulfhydryl
      poisons, only phenylmercuric acetate differentiated between germination in air
      and nitrogen and was nearly 8 times more active under nitrogen. Uptake
      measurements using phenylmercuric acetate and arsenate showed both compounds to
      be in greater concentration under aerobic conditions, thereby rendering unlikely
      any explanation based upon greater permeability under nitrogen. In addition to
      other anomalies, the fact that NaN(3), fluoroacetate and CO inhibited anaerobic
      germination at any concentration requires explanation. It was concluded that the
      general significance and utility of metabolic inhibitor studies in vivo required
      further evaluation.

PMID- 16656685
TI  - Germination of Excised Fraxinus ornus Embryos With and Without Phleomycin.
AB  - In excised embryos of Fraxinus ornus, the first macroscopic sign of germination
      is a curvature near the root apex. Histological studies show that this curvature
      is due to cell elongation on the convex side and is accompanied by cell division.
      Metabolic changes, manifested by the disintegration of protein bodies and tissue
      differentiation, also occur during this time. In embryos treated with phleomycin
      cell division is completely inhibited but elongation, root hair formation,
      disintegration of protein bodies, and differentiation are still detectable.
      Phleomycin also drastically inhibits the formation of chlorophylls and the fresh
      weight increase of embryos.

PMID- 16656686
TI  - Studies on ribosomes from barley leaves. Changes during senescence.
AB  - The effect of sucrose, Mg(2+) and deoxycholate on the yield of ribosomes from
      barley leaves was determined and the changes in the amount and the composition of
      ribosomes during senescence of intact and excised first seedling leaves were
      examined.The extraction medium containing 20 mm tris-HCl, 0.25 m sucrose, 1 mm
      MgCl(2) and 0.5% deoxycholate (pH 7.8) gave the maximum yield of polyribosomes
      and ribosomes. That polyribosomes were not non-specific aggregates was suggested
      by their capacity to synthesize nascent protein. During senescence of both intact
      and excised leaves polyribosomes and ribosomes were lost and the ribosomes
      polyribosomes which originally contained 48% protein and 52% RNA showed
      substantial decline in the protein content during senescence indicating the
      degradation of ribosomes and the loss of their function.

PMID- 16656687
TI  - The effects of light on a circadian rhythm of conidiation in neurospora.
AB  - The expression of a circadian rhythm of conidiation by timex, a strain of
      Neurospora crassa, is inhibited by growth in continuous white light. The action
      spectrum for this effect has a strong peak (with minor subpeaks) in the blue
      region of the visible spectrum, and a broad shoulder in the near ultraviolet.
      This action spectrum suggests that a carotenoid or flavin compound may be the
      photoreceptor, but does not allow one to determine conclusively whether the
      receptor is indeed a carotenoid, flavin, or some other unrelated pigment. Two
      lines of evidence suggest that a carotenoid is not the photoreceptor. First, the
      in vivo absorption spectrum of timex (representing the sum of the spectra of the
      individual pigments present, predominantly carotenoids) has peaks at wavelengths
      10 to 20 mmu longer than those of the action spectrum peaks. Second, an albino
      timex has normal photosensitivity, a situation requiring that the photoreceptor,
      if carotenoid, be a quantitatively minor constituent of the total carotenoid
      complement.The magnitude and direction of phase-shift resulting from a standard
      dose of white light given at different times in the daily cycle of timex varies
      in the manner reported for other organisms. Additional phase-shift experiments
      have shown that there are no major transients in the attainment of a new
      equilibrium after a phase-shifting perturbation, and that 2 light reactions
      (rapidly and slowly saturating) may be involved in the phase-shift response.

PMID- 16656688
TI  - Floral Inhibition of Biloxi Soybean During a 72-hour Cycle.
AB  - The inhibitory effect of light interruptions given during the photophobe phases
      of a 72-hour cycle was studied with Biloxi soybean [Glycine max (L.) Merr.]. The
      basic 72-hour cycle consisted of 8 hours of light followed by 64 hours of
      darkness and was repeated 7 times. Supplementary white light treatments given at
      the twenty-fourth and/or forty-eighth hour of the cycle (photophil phases)
      promoted the flowering levels of the controls and kept light treatments given at
      the most inhibitory points from inhibiting flowering completely. Such
      supplementary light treatments did not affect the time of maximum sensitivity to
      light interruptions. When 30-minute light breaks were used, maximum inhibition
      occurred at the 16-, 43-, and 63-hour points. The duration of the light breaks
      affected the time of maximum inhibition when given during the second photophobe
      phase. The time of maximum inhibition occurred earlier with 4-hour light breaks
      than with either 3-minute or 2-hour light interruptions.Three-minute red light
      interruptions produced essentially the same effect as 3-minute white light
      interruptions. Such treatments inhibited flowering completely in the first
      photophobe phase, inhibited flowering to only a small degree in the second
      photophobe phase, and inhibited flowering to an intermediate degree in the third
      photophobe phase. Far-red light interruptions strongly inhibited flowering in the
      first photophobe phase, especially when given early in the dark period. Three
      minutes of supplementary white light given at the twenty-fourth or forty-eighth
      hour of the cycle partially overcame the inhibitory effect of far-red light. Four
      hours of supplementary white light at these times completely overcame the far-red
      inhibition.

PMID- 16656689
TI  - Biosynthesis of (-)-Kaurene in Cell-free Extracts of Immature Pea Seeds.
AB  - Mevalonate-(14)C was incorporated into (-)-kaurene-(14)C in cell-free extracts of
      immature pea (Pisum sativum L.) seeds. The identification of (14)C-product as (-)
      kaurene was based on: A) comparison with authentic (-)-kaurene on thin-layer and
      gas-liquid chromatography; and B) oxidation of (14)C-product and (-)-kaurene with
      osmium tetroxide to form the common derivative kaurane-16,17-diol. The enzyme
      system is heat labile and is dependent upon ATP and Mg(2+) or Mn(2-), with Mn(2+)
      being a more effective activator than Mg(2+). The reaction rate was proportional
      to enzyme concentration in reaction mixtures containing 0.45 to 1.8 mg protein
      n/ml, and was linear with time through 120 minutes in standard reaction mixtures.
      Enzyme preparations from immature seeds of tall and dwarf peas appeared to
      synthesize (-)-kaurene at the same rate. Synthesis of (-)-kaurene was readily
      inhibited by Amo-1618. (2-Chloroethyl)-trimethylammonium chloride (CCC) also
      inhibited (-)-kaurene synthesis; however, approximately 1000-fold higher
      concentrations of CCC were required to evoke the same percentages of inhibition
      as Amo-1618.

PMID- 16656690
TI  - Properties of Higher Plant Mitochondria. III. Effects of Respiratory Inhibitors.
AB  - The effects of representative respiratory inhibitors were investigated on the
      coupled respiration of mung bean mitochondria using succinate and l-malate as
      substrates. The inhibitors studied were: (I) malonate, (II) amytal and rotenone,
      (III) antimycin A and 2-n-nonyl-4-hydroxyquinoline N-oxide (NOQNO), and (IV)
      cyanide and azide.Malonate inhibition of succinate oxidation follows a classical
      type of competitive inhibition with an inhibitor dissociation constant of 0.13
      mm. There is no inhibition detectable when malate is used as substrate. In
      contrast to animal mitochondria, amytal is capable of inhibiting 20 to 40% of
      succinate oxidation and 90 to 100% of malate oxidation, but inhibition due to
      rotenone amounts to only 0 to 20% of succinate oxidation and 40 to 50% of malate
      oxidation. The half-maximal inhibition caused by amytal occurs at 2 to 2.5 mm and
      that by rotenone at 3 mmumoles/mg protein.The maximal inhibition caused by either
      antimycin A or NOQNO is 70 to 80% of the state 3 respiration. Very little
      inhibition was observed on the state 4 respiration, and both inhibitors were
      capable of titrating stoichiometrically with mitochondrial protein with identical
      titers, 0.22 mmumoles/mg protein for half-maximal inhibition. They differ,
      however, in that NOQNO does uncouple oxidative phosphorylation in mung bean
      mitochondria, but antimycin A does not do so. Both cyanide and azide inhibit the
      state 3 rate 65 to 80%. Inhibition of state 4 respiration can be up to 50% by
      cyanide, while almost none by azide. Uncoupling action was noted with cyanide,
      but very little with azide.It is concluded that the second state 3 rate of
      succinate oxidation includes 80% succinoxidase, the remaining 20% being
      contributed by the NADH pathway. Malate oxidation apparently does not involve
      succinoxidase. Malate oxidation is completely sensitive to amytal, but only 50%
      inhibited by rotenone. A difference between animal and plant mitochondria appears
      to be in the flavoproteins associated with NADH oxidation.From the observations
      that antimycin A, NOQNO, cyanide, and azide do not cause complete inhibition, it
      is suggested that a leakage of electrons to oxygen exists before the site of
      inhibition of antimycin A or NOQNO.

PMID- 16656691
TI  - Physical nature of irreversible deformation of plant cells.
AB  - Etiolated mung bean hypocotyl segments were incubated in 0.25 m mannitol
      solutions with indoleacetic acid. They were then deformed mechanically with a
      longitudinal tensile force at a constant strain rate. The magnitudes of the
      mechanical forces were comparable to those of the hydrostatic forces existing in
      normally growing tissues. Each segment was repeatedly deformed and returned to
      zero force. The total deformation was increased at each cycle.The irreversible
      and elastic changes in length and diameter were measured for each deformation and
      the changes in surface area and volume calculated. In addition the applied stress
      and the work of irreversible and of elastic deformation were determined as
      functions of deformation.It was found that irreversible elongation, irreversible
      change in surface area and total change in surface area all were linear functions
      of total imposed elongation. However, very little change in volume occurred
      during the deformations.The work of irreversible deformation was found to be
      independent of temperature between 8 degrees and 25 degrees . It was also
      virtually independent of rate of deformation measured over a 5-fold range of
      deformation rates.From these results it is concluded that the irreversible
      deformation of mung bean hypocotyl tissue occurs by plastic deformation rather
      than by viscous flow. Thus, the irreversible deformation occurred as a result of
      breaking cross-links of a cross-linked polymer system.

PMID- 16656692
TI  - Flowering Responses of the Long-day Plant Lemna gibba G3.
AB  - Lemna gibba L., strain G3, exhibits a qualitative long-day flowering response
      with a critical daylength on a 24-hour cycle of about 10 hours. Evidence is
      presented that the onset of daughter frond formation in a given frond inhibits
      the activity of the flowering meristem. Consequently, flower induction can only
      occur in fronds smaller than about 0.05 to 0.07 mm long. Although a minimum of 1
      long day seems to be sufficient to induce the formation of flower primordia, at
      least 6 long days are required to obtain mature flowers since long days are also
      required for the early stages of flower development. The critical night length on
      24, 48 and 72-hour cycles is respectively 14, 16, and 18 to 22 hours. The close
      similarity between the critical night length for the different cycle lengths is
      explained in terms of an inhibitory effect of darkness both on flower initiation
      and flower development. A 10-hour dark period is more inhibitory to flowering on
      a 36-hour cycle than on 24, 48, 60 or 72-hour cycles. It is suggested that
      darkness inhibits flowering through the formation of a light-labile flower
      inhibitor which acts to inhibit the functioning of the flowering stimulus.

PMID- 16656693
TI  - Aspects of clock resetting in flowering of xanthium.
AB  - Flowering is induced in Xanthium strumarium by a single dark period exceeding
      about 8.3 hours in length (the critical night). To study the mechanism which
      measures this dark period, plants were placed in growth chambers for about 2 days
      under constant light and temperature, given a phasing dark period terminated by
      an intervening light period (1 min to several hrs in duration), and finally a
      test dark period long enough normally to induce flowering. In some experiments,
      light interruptions during the test dark period were given to establish the time
      of maximum sensitivity.If the phasing dark period was less than 5 hours long, its
      termination by a light flash only broadened the subsequent time of maximum
      sensitivity to a light flash, but the critical night was delayed. In causing the
      delay, the end of the intervening light period was acting like the dusk signal
      which initiated time measurement at the beginning of the phasing dark period.If
      the phasing dark period was 6 hours or longer, time of maximum sensitivity during
      the subsequent test dark period was shifted by as much as 10 to 14 hours. In this
      case the light terminating the phasing dark period acted as a rephaser or a dawn
      signal.Following a 7.5-hour phasing dark period, intervening light periods of 1
      minute to 5 hours did not shift the subsequent time of maximum sensitivity, but
      with intervening light periods longer than 5 hours, termination of the light acts
      clearly like a dusk signal. The clock appears to be suspended during intervening
      light periods longer than 5 to 15 hours. It is restarted by a dusk signal. There
      is an anomaly with intervening light periods of 10 to 13 hours, following which
      time of maximum sensitivity is actually less than the usual 8 hours after
      dusk.Ability of the clock in Xanthium to be rephased, suspended, restarted, or
      delayed, depending always upon conditions of the experiment, is characteristic of
      an oscillating timer and may confer upon this plant its ability to respond to a
      single inductive cycle. It is suggested that phytochrome may influence only the
      phase of the clock and not other aspects of flowering such as synthesis of
      flowering hormone.

PMID- 16656694
TI  - Gluconeogenesis from amino acids in germinating castor bean endosperm and its
      role in transport to the embryo.
AB  - During germination of the castor bean all of the contents of the endosperm are
      ultimately transported to the embryo through the cotyledon or respired. A net
      loss of nitrogen from the endosperm begins about the fourth day, i.e. at the time
      when embryo growth and fat breakdown are also beginning. Amino acid analysis of
      the exudate from the cotyledons, still enclosed in the endosperm, showed that the
      amounts of aspartate, glutamate, glycine, and alanine were very low and that
      glutamine made up 40% of the amino acids in the exudate.Amino acids labeled with
      (14)C were applied to intact excised endosperms to follow utilization. Aspartate,
      glutamate, alanine, glycine, serine, and leucine were converted to sugar to
      varying extents. Proline, arginine, valine, and phenylalanine were not
      appreciably converted to sugars. Proline and glutamate were converted to
      glutamine. When (14)C-glutamate, aspartate, and alanine were added to the outer
      endosperm of intact seedlings, only sugars and glutamine contained appreciable
      label in the exudate. When (14)C-valine was added, it was virtually the only
      labeled compound in the exudate.The results show that amino acids which on
      deamination can give rise to intermediates in the pathway of conversion of fat to
      sucrose are largely converted to sucrose and the nitrogen transported as
      glutamine. Other amino acids released from the endosperm protein are transported
      intact into the seedling axis. Some carbon from the gluconeogenic amino acids is
      also transported as glutamine.

PMID- 16656695
TI  - Gibberellic Acid-induced synthesis of protease by isolated aleurone layers of
      barley.
AB  - The production of protease by isolated aleurone layers of barley in response to
      gibberellic acid has been examined. The protease arises in the aleurone layer and
      is mostly released from the aleurone cells. The courses of release of amylase and
      protease from aleurone layers, the dose responses to gibberellic acid and the
      effects of inhibitors on the production of both enzymes are parallel. As is the
      case for amylase, protease is made de novo in response to the hormone. These data
      give some credence to the hypothesis that the effect of gibberellic acid is to
      promote the simultaneous synthesis and secretion of a group of hydrolases.

PMID- 16656696
TI  - Preparation of radioactive gibberellin a(1) and its metabolism in dwarf peas.
AB  - Gibberellin A(1)-3,4-(3)H was prepared by selective catalytic reduction of
      gibberellic acid with a mixture of tritium and hydrogen. (3)H-GA(1) was applied
      at physiological concentrations to dwarf peas and the metabolism of the hormone
      was investigated. (3)H-GA(1) was converted to an acidic, biologically active
      compound. Radioactive but biologically inactive compounds were also found in the
      neutral fraction and could not be converted to acidic gibberellins by hydrolysis.
      No attachment of gibberellin to any macromolecular fraction was evident.

PMID- 16656697
TI  - Photosynthetic reactions of chloroplasts with unusual structures.
AB  - Photosynthetic reactions of whole leaves and isolated chloroplasts from various
      mutants of Nicotiana tabacum have been correlated to the lamellar structure seen
      in electron micrographs of the chloroplasts. In this way it could be established
      that a fully active photosystem I can be associated with single unfolded
      thylakoids. The complete photosynthetic electron transport system including the
      oxygen evolving apparatus of photosystem II, on the other hand, appears to
      require a close packing of at least 2 thylakoids. The unusual high capacity for
      photosynthesis observed earlier for leaves of certain aurea mutants is reflected
      by a correspondingly high activity of the isolated chloroplasts in the Hill
      reaction. These chloroplasts contain extended areas where 2 thylakoids touch by
      forming simple lamellar overlappings instead of the familiar stacks of lamellar
      discs.

PMID- 16656698
TI  - Carbohydrate and Lipid Metabolism During Germination of Uredospores of Puccinia
      graminis tritici.
AB  - Uredospores of Puccinia graminis (Pers.) tritici (Eriks. and Henn.) were
      uniformly labeled with (14)C by permitting the host (Triticum aestivum L.) to
      carry out photosynthesis in (14)CO(2) during the process of spore production by
      the obligate parasite. The use of (14)C labeled spores provided advantages in a
      study of the utilization of endogenous substrates at frequent intervals with
      small amounts of spores under conditions conducive to germination.Because of
      previous uncertainties about the nature of the substrates of importance to
      germination, a detailed study of carbohydrate and lipid components, both in the
      spores and in the germination medium, was made during the first 7 hours after
      placing the spores on aqueous media. Diethyl ether and 80% ethanol soluble
      metabolites each constituted approximately 20% of the total spore carbon. During
      the first hour nearly 60% of the 80% alcohol solubles disappeared from the spores
      while the total ether soluble material did not change appreciably. A significant
      part of the 80% ethanol soluble materials appeared in the germination
      medium.During germination and germ tube extension, there was rapid utilization of
      trehalose, arabitol and mannitol even though appreciable amounts of these
      materials were present as exogenous pools in the germination medium. Although the
      total amounts of ether soluble components did not change as drastically as the
      carbohydrate fraction, there was extensive utilization of palmitic, oleic,
      linolenic and 9,10-epoxyoctadecanoic acids.The results indicate that the
      germination process in spores of obligate parasites is not based solely on the
      utilization of lipids and some possible roles of the changes in internal and
      external pools of soluble carbohydrates are discussed.

PMID- 16656699
TI  - An Electron Spin Resonance Study of Manganese in Wild-Type and Mutant Strains of
      Chlamydomonas reinhardi.
AB  - Changes in the intensity of the electron spin resonance signal of divalent
      manganese were found to occur in suspensions of wild-type Chlamydomonas
      reinhardi. The observed manganese signal decreased in the light and increased in
      the dark. Through the use of a continuous-flow system it was possible to
      determine that the manganous ions responsible for the observed signal were
      localized solely in the medium. Changes in the signal intensity associated with
      wild-type cells were independent of the ability of fragments prepared from these
      cells to perform the Hill reaction with 2,6-dichlorophenol-indophenol (DPIP) as
      the oxidant.The manganese signal changes were still evident, though smaller, in
      cell suspensions of wild-type cells treated with 3-(3,4-dichlorophenyl)-1, 1
      dimethylurea, and in mutant strains unable to carry out the Hill reaction, ac-115
      and ac-141.From these data it is concluded that the changes in intensity of the
      manganese resonance are not related to the function of manganese in
      photosynthesis but may reflect the capacity of cells for ion uptake in the light.

PMID- 16656700
TI  - Ethylene and auxin participation in pollen induced fading of vanda orchid
      blossoms.

PMID- 16656701
TI  - Fucosterol Reduction to Clionasterol in vivo by Chlorella ellipsoidea.

PMID- 16656702
TI  - Influence of Purines and Pyrimidines on Cold Hardiness of Plants. III. Associated
      Changes in Soluble Protein and Nucleic Acid Content and Tissue pH.
AB  - When applications of certain purines and pyrimidines enhanced the development or
      maintenance of cold hardiness, the content of water-soluble, trichloroacetic acid
      precipitable protein and nucleic acids and tissue pH were higher in treated
      plants than in controls. The reverse was generally true when the treated plants
      were less cold hardy than the controls. In some instances, the purines and
      pyrimidines increased the content of these nitrogenous constituents in a nonhardy
      variety to a level equal to that found in untreated plants of a hardy variety.

PMID- 16656703
TI  - Localization of the ca-mediated apparent ion selectivity in the cross sectional
      volume of soybean roots.
AB  - A major portion of the calcium in a soybean root appears to be in less than 10%
      of the root volume. Specifically, Ca is considered to be almost entirely
      localized in the epidermal cell layer. This relationship was established from
      consideration of rates and extent of ion absorption and ion interactions during
      the absorption process.Presence of calcium at the root-solution interface was
      associated with a change in the apparent selectivity of K over Mg by soybean
      roots. Accumulation of calcium by soybean roots was negligible.

PMID- 16656704
TI  - Low Energy Effects of Light on Growth and Pigment Content in a Yellow-in-the-Dark
      Mutant of Chlamydomonas reinhardi.
AB  - The y-2 mutant of Chlamydomonas reinhardi differs from the wild type in being
      unable to synthesize chlorophyll in the dark and in a requirement for catalytic
      amounts of light for organotrophic growth. Light-grown y-2 cells given acetate
      are capable of the equivalent of 9 to 10 divisions when placed in darkness.
      Cultures adapt gradually to dim white or monochromatic light and after 8 to 10
      generations assume a steady state with respect to growth and pigment content.Two
      energetically distinct light reactions promote the growth of y-2 on acetate. A
      low energy requirement is satisfied at about 0.1 muw/cm(2) of white light which
      results in a growth rate of 0.5 log unit per day. A high energy response, which
      saturates at 2000 muw/cm(2) and a growth rate of 0.9 log unit per day, is
      probably attributable to net photosynthesis. An action spectrum for the low
      energy growth response contains a broad major peak in the blue between 462 and
      502 nm and a minor peak in the far-red between 700 and 736 nm. All intermediate
      wavelengths have low but positive activity. The action spectrum was investigated
      with y-2 cultures that were grown for many generations under steady-state
      conditions in growth-limiting monochromatic light. Many wavelengths resulted in a
      selection pressure that strongly favored a strain of green-in-the dark cells that
      usually appeared after 5 to 8 generations of light-limited growth. Under the low
      light intensity of these experiments (0.15 +/- 0.05 muw/cm(2)) the green strain
      was much richer in chlorophyll than y-2 and divided more rapidly with the
      consequence that y-2 was generally replaced in the course of a few generations.
      Consideration of the results led to the conclusion that both chlorophyll and
      carotenoids act as photoreceptors in the low energy growth response of y-2.

PMID- 16656705
TI  - Light stimulation of cold acclimation: production of a translocatable promoter.
AB  - The light stimulation of cold acclimation of Hedera helix L. var. Thorndale has
      been shown to result in the production of translocatable promoters of hardiness.
      Movement of the promoters from an illuminated donor portion to a darkened
      receptor portion was demonstrated. The majority of transport was acropetal
      through the phloem and to a much lesser degree basipetal through the xylem. In
      the early stages of hardening, transport was strictly acropetal. It is suggested
      that acropetal transport is under the influence of a mobilizing center located in
      the apex of the plant. Mobilization of the promoters of hardiness was induced by
      applications of (6)N-benzyladenine. Attempts to characterize the light-generated
      promoters through fixation of (14)CO(2) and subsequent translocation of (14)C
      labeled compounds from the illuminated donor to the darkened receptor indicated
      that the translocatable promoting material was either some component of the Dowex
      1 fraction or sucrose. Furthermore, the hardiness of leaves was significantly
      increased by sucrose solutions but not by equi-molar solutions of glucose,
      galactose or mannitol.

PMID- 16656706
TI  - Survival of plant tissue at super-low temperatures v. An electron microscope
      study of ice in cortical cells cooled rapidly.
AB  - Experiments were carried out with cortical cells in twig bark of mulberry trees
      in winter in order to clarify the mechanism of survival at super-low temperatures
      with rapid cooling and rewarming. Attention was given to the relation between the
      existence of intracellular ice crystals and survival.Cortical cells were cooled
      rapidly by direct immersion into liquid nitrogen or isopentane cooled at various
      temperatures. After immersion, they were freeze-substituted with absolute ethanol
      at -78 degrees . They were then embedded, sectioned and examined under the
      electron microscope for the presence and distribution of cavities left after ice
      removal.Cells were found to remain alive and contain no ice cavities when
      immersed rapidly into isopentane baths kept below -60 degrees . Those cells at
      intermediate temperatures from -20 degrees to -45 degrees , were almost all
      destroyed. It was also observed that many ice cavities were contained in the
      cells immersed rapidly into isopentane baths at -30 degrees . The data seem to
      indicate that no ice crystals were formed when cooled rapidly by direct immersion
      into isopentane baths below -60 degrees or into liquid nitrogen.The tissue
      sections immersed in liquid nitrogen were rapidly transferred to isopentane baths
      at temperatures ranging from -70 degrees to -10 degrees before rapid rewarming.
      There was little damage when samples were held at temperatures below -50 degrees
      for 10 minutes or below -60 degrees for 16 hours. No cavities were found in these
      cells. Above -45 degrees , and especially at -30 degrees , however, all cells
      were completely destroyed even when exposed only for 1 minute. Many ice cavities
      were observed throughout these cells. The results obtained may be explained in
      terms of the growth rate of intracellular ice crystals.

PMID- 16656707
TI  - Survival of Plant Tissue at Super-Low Temperature VI. Effects of Cooling and
      Rewarming Rates on Survival.
AB  - The survival rates of the cortical parenchymal cells of mulberry tree were
      determined as a function of cooling and rewarming rates. When cooling was carried
      out slowly at 1 degrees to 15 degrees per minute, all of the cells still remained
      viable even when rewarmed either rapidly or slowly. Survival rates gradually
      decreased to zero as the cooling rate increased from about 15 degrees to 2000
      degrees per minute. In the intermediate cooling rates, when the cells were cooled
      at the rates lower than 14 degrees per minute, from -2.2 degrees to about -10
      degrees , these cells could survive subsequent rapid cooling and
      rewarming.However, at cooling rates above 1000 degrees per minute and with rapid
      rewarming, the effect of cooling rate reversed and survival increased, reaching a
      maximum at about 200,000 degrees per minute. As the cooling rate increased above
      15 degrees per minute, survival rates became increasingly dependent on the
      rewarming rate, with rapid rewarming becoming less deleterious than slow
      rewarming.The temperature range at which damage occurred during rewarming
      following removal from liquid nitrogen and in which growth rate of ice
      crystallization was greatest, was -30 degrees to -40 degrees . The survival rates
      even in the prefrozen cells at -30 degrees decreased considerably by keeping them
      at -30 degrees for 10 minutes after removal from liquid nitrogen. This fact
      indicates that intracellular freezable water remains to some degree even in the
      prefrozen cells at -30 degrees . After removal from liquid nitrogen, all cells
      retained their viability, when they were passed rapidly through a temperature
      range between -50 degrees and -2.5 degrees within about 2 seconds, namely at the
      rates greater than 1000 degrees per minute.These observations are explained in
      terms of the size of the crystals formed within the cortical cells.

PMID- 16656708
TI  - Uncoupling of energy-linked functions of corn mitochondria by linoleic Acid and
      monomethyldecenylsuccinic Acid.
AB  - Linoleic acid and monomethyldecenylsuccinic acid were tested as uncoupling agents
      for energy linked functions of corn mitochondria. 2,4-dinitrophenol was used as a
      standard for comparison. Both compounds uncoupled oxidative phosphorylation,
      released oligomycin-blocked respiration, and accelerated adenosine
      triphosphatase. Linoleic acid uncoupled calcium-activated phosphate accumulation
      and the increase in light scattering that accompanies the accumulation. Unlike
      dinitrophenol, linoleic acid at 0.1 mm had a destructive effect on membrane
      semipermeability. Kinetic studies indicated that dinitrophenol and linoleic acid
      compete with phosphate for active sites in oxidative phosphorylation.Some
      linoleic acid is taken up by respiring mitochondria and a major share of the
      uptake is incorporated into phospholipids. Calcium ion and oligomycin promote the
      uptake, but coenzyme A does not. It is deduced that fatty acid probably attacks
      the non-phosphorylated intermediate, I approximately X, producing X approximately
      acyl. Uncoupling results from breakdown of X approximately acyl, but sufficient X
      approximately acyl is maintained to serve as a source of activated fatty acid.

PMID- 16656709
TI  - Temperature and plant adaptation. I. Interaction of temperature and light in the
      synthesis of chlorophyll in corn.
AB  - The effect of temperature and light intensity have been studied in relation to
      the greening of etiolated corn (Zea mays cv. Pioneer 309-B) seedlings.
      Chlorophyll accumulation is rapid at high temperature (28 degrees ) under all
      conditions of light intensity. At low temperature (16 degrees ), and particularly
      in combination with high light intensity (3000-4500 ft-c), the accumulation of
      both chlorophyll and carotene is inhibited.Low pigment content at 16 degrees is
      not directly due to a block in the pigment synthesizing mechanism, but rather to
      the photodestruction of chlorophyll prior to its stabilization in the membrane
      structure of the chloroplast lamellae. The parallel reduction in carotene content
      at high light intensity is probably a contributing factor, because of its role in
      protecting chlorophyll from photodestruction. The greater severity of photo
      oxidation of chlorophyll at low temperature in corn when compared with wheat,
      appears to be due to a slower rate of protochlorophyllide synthesis and
      subsequent esterification. Thus in corn at 16 degrees there is a prolongation of
      the photosensitive stage during chlorophyll synthesis. Photo-oxidation at 16
      degrees has also been shown to be a function of the incident light energy, with
      the photosynthetic pigments acting as receptors for their own destruction.In
      comparison with the behavior of corn, wheat seedlings green rapidly at high light
      intensity at both 16 degrees and 28 degrees . This contrasting temperature
      response with respect to chlorophyll synthesis may underlie a fundamental
      difference in adaptation of these 2 species to growth in the temperate zones of
      the world.

PMID- 16656710
TI  - Chlorophyll Formation and Photosynthetic Competence in Euglena During Light
      Induced Chloroplast Development in the Presence of 3, (3,4-dichlorophenyl) 1,1
      Dimethyl Urea (DCMU).
AB  - The possibility that photosynthetic competence is gratuitous for light-induced
      chloroplast development in Euglena gracilis var. bacillaris was examined by
      incubating dark-grown resting cells in the light with DCMU, an inhibitor of
      photosynthesis. Under these conditions photosynthetic carbon dioxide fixation was
      inhibited essentially completely at all times during chloroplast development, but
      about 70% of the chlorophyll was formed with essentially the same pattern of
      accumulation found for cells incubated in the absence of the inhibitor. Electron
      microscopy of cells incubated with DCMU in the light revealed the formation of
      morphologically recognizable chloroplasts having comparable overall dimensions
      and structural elements to those found in normally developed chloroplasts, but
      frequently lacking a readily detectable pyrenoid with paramylum sheaths, and
      often containing increased numbers of discs per lamella. Such abnormalities are
      considered minor since upon removal of DCMU by centrifugation, the cells usually
      regained almost full photosynthetic competence on a chlorophyll basis.It is
      concluded that photosynthetic competence is not necessary for chloroplast
      development in Euglena and supports the hypothesis, already suggested from other
      evidence, that light induction results in activation of synthetic machinery
      external to the developing chloroplast.

PMID- 16656711
TI  - The Biosynthesis of Some Isothiocyanates and Oxazolidinethiones in Rape (Brassica
      campestris L.).
AB  - The incorporation of the radioactivity from acetate-1-(14)C, acetate-2-(14)C, dl
      methionine-1-(14)C, dl-methionine-2-(14)C, dl-methionine-3,4-(14)C, dl
      homomethionine-2-(14)C, dl-allyl-glycine-2-(14)C, and dl-2-amino-5
      hydroxyvalerate-2-(14)C into the aglycones of progoitrin, gluconapin, and
      glucobrassicanapin of maturing rape plants (Brassica campestris L.) was
      investigated. Radioactivity from dl-methionine-2-(14)C, dl-methionine-3,4-(14)C,
      dl-homomethionine-2-(14)C, and acetate-2-(14)C were incorporated into the 3 major
      thioglucosides. The other organic compounds were poorly incorporated except for
      dl-allylglycine-2-(14)C into glucobrassicanapin. The results obtained suggest
      that the rape plant can synthesize amino acids by the condensation of acetate (as
      acetyl CoA) to alpha-keto acids to yield a homologue of the original amino acid.
      These newly formed amino acids are then employed to synthesize the 3 major
      thioglucosides.

PMID- 16656712
TI  - Loss of organic acids, amino acids, k, and cl from barley roots treated
      anaerobically and with metabolic inhibitors.
AB  - Excised roots of barley (Hordeum vulgare, var. Campana) lost organic acids, amino
      acids, K(+), and Cl(-) within 15 minutes after initiation of anaerobic treatment
      or treatment with NaCN and 2,4-dinitrophenol. Initial loss of organic acids when
      roots were placed under N(2) is attributed to a decarboxylation reaction,
      possibly catalyzed by phosphoenolpyruvate carboxykinase. Organic and amino acids
      began to leak from the roots to the bathing medium after 1 to 2 hours under N(2),
      indicating injury to cell membranes. During the first hour of anaerobic
      treatment, K(+) loss from low-salt roots was equivalent to organic acid loss.
      Potassium loss from roots containing high levels of KCl was approximately equal
      to organic acid plus amino acid loss; and Cl(-) loss was approximately equal to
      amino acid loss. It is postulated that, within cells, organic acids may
      electrostatically bind an equivalent quantity of cations and that amino acids may
      bind an equivalent quantity of both cations and anions.

PMID- 16656713
TI  - Incorporation of methanol into pectic substance.
AB  - Others have shown that l-methionine is utilized in the biosynthesis of methyl
      ester groups in pectic substance. Methanol, like l-methionine, is used for methyl
      ester biosynthesis by detached parsley leaves (Petroselinum crispum). When a
      combination of methanol-(3)H and methanol-(14)C is given to parsley leaves,
      methanol recovered from pectic substance by alkaline hydrolysis has a (3)H/(14)C
      ratio about one-fourth that of the mixture administered. Unlike l-methionine,
      methanol is oxidized prior to its utilization as a carbon source for methyl ester
      biosynthesis.Parsley leaves given methyl d-galacturonate-methyl-(14)C also form
      pectic substance in which methyl groups are labeled but incorporation appears to
      proceed by way of methanol metabolism after hydrolysis of methyl d-galacturonate.

PMID- 16656714
TI  - Translocation of C Sucrose in Sugar Beet during Darkness.
AB  - The time-course of arrival of (14)C translocate in a sink leaf was studied in
      sugar beet (Beta vulgaris L. cultivar Klein Wanzleben) for up to 480 minutes of
      darkness. Following darkening of the source leaf, translocation rapidly declined,
      reaching a rate approximately 25% of the light period rate by 150 minutes.
      Comparison of data from plants that were girdled 1 cm below the crown with data
      from ungirdled plants indicates that after about 150 minutes darkness the beet
      root becomes a source of translocate to the sink leaf. After about 90 minutes
      darkness, starch-like reserve polysaccharide from the source leaf begins to
      contribute (14)C to ethanol soluble pools in that leaf. Because of a 15% isotope
      mass effect, sucrose, at isotopic saturation, reaches a specific activity which
      is about 85% of the level of the supplied CO(2). The source leaf sucrose specific
      activity remains at the isotopic saturation level for about 150 minutes of
      darkness, after which time input from polysaccharide reserves causes the specific
      activity to drop to about 55% of that of the supplied CO(2). Sucrose specific
      activity determinations, polysaccharide dissolution measurements, and pulse
      labeling experiments indicate that following partial depletion of the sucrose
      pool, source leaf polysaccharide contributes to dark translocation. Respired
      CO(2) from the source leaf appears to be derived from a pool which, unlike
      sucrose, remains at a uniform specific activity.

PMID- 16656715
TI  - Regulation of Nitrate Reductase Activity in Corn (Zea mays L.) Seedlings by
      Endogenous Metabolites.
AB  - Primary and secondary metabolites of inorganic nitrogen metabolism were evaluated
      as inhibitors of nitrate reductase (EC 1.6.6.1) induction in green leaf tissue of
      corn seedlings. Nitrite, nitropropionic acid, ammonium ions, and amino acids were
      not effective as inhibitors of nitrate reductase activity or synthesis.
      Increasing alpha-amino nitrogen and protein content of intact corn seedlings by
      culture techniques significantly enhanced rather than decreased the potential for
      induction of nitrate reductase activity in excised seedlings.Secondary
      metabolites, derived from phenylalanine and tyrosine, were tested as inhibitors
      of induction of nitrate reductase. Of the 9 different phenylpropanoid compounds
      tested, only coumarin, trans-cinnamic and trans-o-hydroxycinnamic acids inhibited
      induction of nitrate reductase.While coumarin alone exhibited a relatively
      greater inhibitory effect on enzyme induction than on general protein synthesis
      (the latter measured by incorporation of labeled amino acids), this differential
      effect may have been dependent upon unequal rates of synthesis and accumulation
      with respect to the initial levels of nitrate reductase and general proteins.
      Because of the short half-life of nitrate reductase, inhibitors of protein
      synthesis in general could still achieve differential regulation of nitrogen
      metabolism. Coumarin did not inhibit nitrate reductase activity when added
      directly to the assay mixture at 5 mm.Carbamyl phosphate and its chemical
      derivative, cyanate, were found to be competitive (with nitrate) inhibitors of
      nitrate reductase. The data suggest that cyanate is the active inhibitor in the
      carbamyl phosphate preparations.

PMID- 16656716
TI  - Regulation of senescence in bean leaf discs by light and chemical growth
      regulators.
AB  - The senescence of excised discs of primary leaves of Phaseolus vulgaris, L., var.
      Red Kidney was followed by measuring the net breakdown of protein and
      chlorophyll. The chemical growth regulators indoleacetic acid, 2,4
      dichlorophenoxy-acetic acid, gibberellic acid, kinetin, and 6-benzylaminopurine
      were relatively ineffective in retarding senescence in this tissue. White light,
      on the other hand, was very effective in senescence retardation. The response to
      light did not have the characteristics of a low energy (phytochrome) response and
      was blocked by concentrations of 3-(3,4-dichlorophenyl)-1, 1-dimethylurea which
      inhibited photosynthesis in the leaf discs. The light-induced retardation of
      senescence was concluded to be dependent on photosynthesis.

PMID- 16656717
TI  - Serine Transhydroxymethylase of Cauliflower (Brassica oleracea var. botrytis L.):
      Partial Purification and Properties.
AB  - Serine transhydroxymethylase (EC 2.1.2.1) has been purified 46-fold from
      cauliflower (Brassica oleracea var. botrytis L.). The enzyme was completely
      dependent on the presence of tetrahydrofolic acid for the conversion of serine to
      glycine. The addition of pyridoxal phosphate gave a large increase in the
      reaction rate. A double pH optimum was observed with maxima at 7.5 and 9.5. The
      enzyme is specific for l-serine. The d-isomer is neither a substrate nor an
      inhibitor. The Michaelis constants for l-serine, tetrahydrofolic acid, and
      pyridoxal phosphate were 300 mum, 760 mum, and 24 mum, respectively. The addition
      of K(+) also stimulated the reaction rate considerably. The effect was quite
      specific since all other metal ions tested either had very little: influence or
      were extremely inhibitory.

PMID- 16656718
TI  - Allagochrome II. Effects of Light and Substrate on Allagochrome and Chlorogenic
      Acid Levels of Incubated Sunflower Leaf Discs.
AB  - Sunflower leaf discs incubated in the light on carbohydrate substrates exhibit
      several-fold increases in amounts of extractable allagochrome and chlorogenic
      acid. These changes are linear with time, and oxygen is required. The light
      effect saturates at approximately 600 muW/cm(2) "white" light, roughly the
      compensation point for photosynthesis. Red light is as effective as white light.
      Incubation in the dark, or in far red light, produces negligible changes in
      allagochrome and chlorogenic acid content.Sucrose (0.2 m) has been used as the
      standard substrate. At this concentration, glucose and fructose are slightly more
      effective. The optimum temperature range for incubation is 20 to 30 degrees .
      Allagochrome and chlorogenic acid values of both light and dark incubated samples
      decrease between 30 and 50 degrees , approaching zero at 50 degrees . Net light
      effects decrease to zero between 40 and 50 degrees .Of the inhibitors tested, 2,4
      dinitrophenol, hydroxylamine and salicylaldoxime have no effect on light enhanced
      allagochrome and chlorogenic acid values except at high concentrations (which are
      generally deleterious to leaf tissues and cause decreased values for both dark
      and light incubated samples). Net light effects are completely inhibited, without
      changes in values of dark incubated discs, by azide (0.1 to 1 mm) and
      dichlorophenyldimethylurea (1 to 10 mum).Leaf tissues from the xantha mutant of
      Helianthus annuus do not exhibit a light effect. The absence of light effects in
      nonphotosynthetic leaf tissue and the inhibiting effects of photosynthetic
      poisons suggest that the photosynthetic apparatus is somehow involved.An
      hypothesis for light regulated metabolism via phenolic synthesis is discussed.

PMID- 16656719
TI  - Invertase inhibitor from potatoes: purification, characterization, and reactivity
      with plant invertases.
AB  - Invertase inhibitor was extracted from potato tubers and purified nearly 1000
      fold. The purification procedure involved precipitation at pH 4.0, fractionation
      with ammonium sulfate, adsorption on alumina Cgamma gel, and gel filtration on
      Sephadex G-100 and DEAE-Sephadex A-50. The product obtained was homogeneous to
      electrophoresis on polyacrylamide gel. Exclusion chromatography on Sephadex G-100
      indicated a molecular weight of about 17,000. The inhibitor did not inhibit
      yeast, Neurospora, and several plant invertases. It completely inhibited potato
      tuber invertase and a number of other plant invertases. Some plant invertases
      were partially inhibited.

PMID- 16656720
TI  - Biosynthesis of Indoleacetic Acid from Tryptophan-C in Cell-free Extracts of Pea
      Shoot Tips.
AB  - A 2-step, 1-dimensional thin-layer chromatographic procedure for isolating
      indoleacetic acid (IAA) was developed and utilized in investigations of the
      biosynthesis of IAA from tryptophan-(14)C in cell-free extracts of pea (Pisum
      sativum L.) shoot tips. Identification of a (14)C-product as IAA was by (a) co
      chromatography of authentic IAA and (14)C-product on thin-layer chromatography,
      and (b) gas-liquid and thin-layer chromatography of authentic and presumptive IAA
      methyl esters. Dialysis of enzyme extracts and addition of alpha-ketoglutaric
      acid and pyridoxal phosphate to reaction mixtures resulted in approximately 2- to
      3-fold increases in net yields of IAA over yields in non-dialyzed reaction
      mixtures which did not contain additives essential to a transaminase reaction of
      tryptophan. Addition of thiamine pyrophosphate to reaction mixtures further
      enhanced net biosynthesis of IAA. It is concluded that the formation of
      indolepyruvic acid and its subsequent decarboxylation probably are sequential
      reactions in the major pathway of IAA biosynthesis from tryptophan in cell-free
      extracts of Pisum shoot tips. Comparison of maximum net IAA biosynthesis in
      extracts of shoot tips of etiolated and light-grown dwarf and tall pea seedlings
      revealed an order, on a unit protein N basis, of: light-grown tall > light-grown
      dwarf > etiolated tall congruent with etiolated dwarf. It is concluded that the
      different rates of stem elongation among etiolated and light-grown dwarf and tall
      pea seedlings are correlated, in general, with differences in net IAA
      biosynthesis and sensitivity of the tissues to IAA.

PMID- 16656721
TI  - Photosynthesis in Chlorophyllus Stem Tissue and Leaves of Cercidium floridum:
      Accumulation and Distribution of C from CO(2).

PMID- 16656722
TI  - Dye and calcium ascent in dogwood trees.

PMID- 16656723
TI  - Effect of ethylene and gibberellic Acid on auxin synthesis in plant tissues.

PMID- 16656725
TI  - Rapid starch synthesis associated with increased respiration in germinating lily
      pollen.
AB  - In vitro studies of germinating Lilium longiflorum pollen showed that starch
      increased more rapidly during the first 30 minutes of incubation than during the
      next several hours. The period of rapid starch formation coincided with the first
      period of high respiration. An estimate was made of the extra ATP utilized to
      form extra starch during the first 30 minutes, and this estimate indicates that
      starch synthesis accounts for a significant portion of the initial high rate of
      respiration. This pattern of respiration and starch synthesis was not altered
      when pollen germinated in a pentaerythritol medium that could not be metabolized
      instead of the standard sucrose medium.Sucrose was the predominant sugar in
      mature lily pollen. This sugar decreased 50% during several hours incubation in
      pentaerythritol culture medium. Reducing sugars remained low during incubation
      which may indicate that sucrose breakdown is regulated by the rate of utilization
      of hexose units.

PMID- 16656726
TI  - Phosphorylases I and II of Maize Endosperm.
AB  - Two phosphorylases have been found in the endosperm of Zea mays. Phosphorylase I
      is found through all stages of endosperm development and seed germination
      investigated. The other enzyme, phosphorylase II appears only at the stage of
      rapid starch biosynthesis and is not found during germination. At 22 days after
      pollination, the activity of phosphorylase II is 10 times that of phosphorylase
      I. These 2 phosphorylases are separable by column chromatography and behave
      differently in several respects.Phosphorylase I cannot utilize maltose as a
      primer while phosphorylase II does so readily. Furthermore, phosphorylase II can
      synthesize an amylose-like polymer from a "primer free" system after a lag
      phase.Phosphorylase II is inhibited severely at pH 5.8 by ATP, GTP, ADP, and GDP,
      and less drastically by UTP, CTP, UDP and CDP. Phosphorylase I is somewhat
      inhibited by purine nucleotides but not by pyrimidine nucleotides. In all cases,
      the inhibition is pH-dependent. Phosphorylase I is inhibited competitively by ATP
      while phosphorylase II is inhibited non-competitively.Phosphorylase II is
      markedly stimulated by 10 mm Mg(2+) and by 2 mm ethylenediamine tetraacetic acid
      while phosphorylase I is relatively little affected.

PMID- 16656727
TI  - Native growth inhibitors from citrus shoots. Partition, bioassay, and
      characterization.
AB  - A partition method has been devised to separate auxins, gibberellins, and their
      respective inhibitors in plant extracts. Inhibitors counteracting gibberellin
      activity have been detected by a modified barley endosperm bioassay. An inhibitor
      found in young citrus shoots counteracts both auxin and gibberellin activities
      and behaves during partition and ohromatography like abscisin II.

PMID- 16656728
TI  - Phytochrome and Seed Germination. IV. Action of Light Sources With Different
      Spectral Energy Distribution on the Germination of Tomato Seeds.
AB  - Germination of tomato seeds exposed to a single, saturating irradiation from
      light sources of different spectral energy distribution seems to be dependent
      upon the photostationary P(FR)/P(R) ratio established by the irradiation.
      Germination of tomato seeds exposed to prolonged irradiations from the same light
      sources does not seem to be controlled solely by the P(FR)/P(R) ratio induced and
      maintained by the irradiation.

PMID- 16656729
TI  - Swelling and contraction of phaseolus hypocotyl mitochondria.
AB  - Isolated Phaseolus mitochondria will swell spontaneously in buffered KCl and
      contract with an oxidizable substrate or ATP + Mg(2+). The conditions under which
      the mitochondria are swollen affect subsequent contraction, substrate oxidation
      and ion accumulation, but not their oxidative phosphorylation ability. Bovine
      serum albumin reduces the rate of swelling and promotes substrate oxidation,
      contraction and ion accumulation. Swelling of these mitochondria is associated
      with the release of malic dehydrogenase and a loss of membrane integrity. The
      beneficial effects of bovine serum albumin in preserving the energy linked
      functions of Phaseolus mitochondria is discussed.

PMID- 16656730
TI  - Photosynthetic CO(2) Fixation by Green Cymbidium (Orchidaceae) Flowers.

PMID- 16656731
TI  - Effect of the Specific Toxin in Helminthosporium victoriae on Host Cell
      Membranes.
AB  - Helminthosporium victoriae toxin, which affects only hosts of the toxin-producing
      fungus, causes loss of electrolytes from roots, leaves, and coleoptiles of
      treated plants. Root hair cells lost the ability to plasmolyze after 20 minutes
      exposure to toxin in solution; comparable resistant cells retained plasmolytic
      ability during 3 hours exposure. Toxin stopped uptake of exogenous amino acids
      and Pi by susceptible but not by resistant tissue. Incorporation of (32)P into
      organic-P and (14)C-amino acids into protein was blocked in susceptible but not
      in resistant tissue. Apparent free space increased in susceptible but not in
      resistant roots. The increase was evident within 30 minutes, and reached 80% free
      space after 2 hours exposure to toxin. When cell wall-free protoplasts were
      exposed to 0.16 mug toxin/ml, protoplasmic streaming stopped and all plasma
      membranes of susceptible protoplasts broke within 1 hour. Resistant protoplasts
      were not affected significantly. Data support the hypothesis of a primary lesion
      of toxin in the plasma membrane. Effects on synthesis could result from lack of
      transport of exogenous solutes to sites of synthesis. It is possible that all
      other observed effects of toxin are secondary to membrane damage.

PMID- 16656732
TI  - Promotion of growth and invertase activity by gibberellic Acid in developing
      Avena internodes.
AB  - Gibberellic acid (GA(3)) induces invertase activity within 6 hours in Avena stem
      segments that are incubated in the dark at 23 degrees . The maximum amount of
      promotion is about 5 times that of invertase activity in untreated segments.
      GA(3) causes significant promotion of invertase activity at concentrations as low
      as 3 x 10(-5) mum GA(3). The increase in invertase activity elicited by GA(3)
      between 3 x 10(-5) mum and 300 mum closely parallels the growth promotion that is
      caused by GA(3) over this concentration range. In control segments, invertase
      activity rises steeply during the first 6 hours of incubation, then decays slowly
      between 12 and 48 hours. In GA(3)-treated segments, the invertase activity also
      rises during the first 6 hours, parallel to that in control segments and
      continues to rise during the next 42 hours. These changes in invertase activity
      during 48-hour incubation periods do not parallel the changes in growth that
      occur in control and GA(3)-treated segments. Cycloheximide at 10 mug/ml abolishes
      all GA(3)-promoted growth and invertase activity in these segments. Actinomycin D
      at 40 and 80 mug/ml decreases GA(3)-promoted growth by 20% and invertase activity
      by 38 and 44%, respectively. The data clearly support the idea that protein
      synthesis is necessary for GA(3)-promoted growth and invertase activity in Avena
      stem segments.

PMID- 16656733
TI  - Far-red Sensitive Dark Processes Essential for Light- and Gibberellin-induced
      Germination of Lettuce Seed.
AB  - The action of prolonged far-red on seed germination was studied in Lactuca sativa
      L. var. Grand Rapids. Exposure of imbibed seeds to 6 hours far-red before the
      application of gibberellic acid (GA(3)) and thiourea completely prevented
      germination. Using GA(3), this far-red was effective after the sixth hour of
      imbibition. At 6, 12, and 18 hours of imbibition equal durations of far-red had
      equal effects. The kinetics of far-red action was investigated: it was found that
      although far-red for several hours, irrespective of the energy level, was needed
      for maximum inhibition, shorter durations (15 and 30 mins) were also appreciably
      effective provided they were followed by several hours darkness before the supply
      of GA(3). This is taken to indicate the existence of labile product(s) of the
      action of a far-red sensitive pigment. Evidence is provided for the existence of
      promotive dark processes controlled by this pigment, which are essential for
      germination whether triggered by GA(3), thiourea or red-light. A model for the
      operation of the pigment system is proposed and its role in the germination
      mechanism of this seed is discussed.

PMID- 16656734
TI  - The composition of soluble nucleotides in the developing wheat grain.
AB  - A method is described for the extraction and measurement of soluble nucleotides
      from wheat grain. Nucleotides were separated (80-90% recovery) by paper
      chromatography followed by electrophoresis. The nucleotides extracted were ADP
      glucose, ATP, ADP, AMP, and NAD; UDP-glucose, UTP, UDP, and UMP with smaller
      quantities of cytidine nucleotides.In grain sampled at 20 days after anthesis,
      70% of the UDP-glucose was present in the endosperm and the remainder in the
      testa and pericarp; 90% of the ADP-glucose was found in the endosperm. Of the
      four uridine nucleotides UDP-glucose was the most plentiful and the level rose
      from about 330 mmumoles per g fresh weight on the third day after flowering to
      430 mmumoles/g on day 12 and then fell steadily to about 140 mmumoles/g just
      before complete ripening. Levels of 250 mmumoles and 200 mmumoles per g fresh
      weight were recorded for UTP and UDP on day 12. Thereafter the content of UTP
      fell relatively more rapidly than either UDP or UDP-glucose.ATP was the most
      abundant adenine nucleotide and from 7 days after anthesis to day 40 the quantity
      per g fresh weight fell from about 350 mmumoles to 100 mmumoles. The level of ADP
      glucose rose to a maximum of 140 mmumoles/g between days 15 and 21 and then fell
      slightly towards maturity while ADP varied between 50 and 80 mmumoles/g. On day
      20, coinciding with the maximum rate of starch synthesis in the endosperm, the
      concentration of ADP-glucose in this tissue was about 0.3 mm, and that of UDP
      glucose 0.7 mm.The relationship of these results to the mechanism of transfer of
      hexose units from sucrose to starch is discussed.

PMID- 16656735
TI  - Partial chemical characterization of corn root cell walls.
AB  - The present study reports on chemical changes which occur in the cell wall of Zea
      mays during early phases of growth. Roots of seedling corn plants were divided
      into a meristematic zone, the zone of elongation, and the maturation zone, and
      the cell wall isolated from each of these zones. The wall preparations were then
      extracted sequentially to obtain pectin, hemicellulose, cellulose, and lignin
      fractions. Each of these, except for the lignin fraction, was hydrolyzed and the
      resultant sugars isolated, identified, and estimated quantitatively. Quantitative
      analysis of the products of hydrolysis of these fractions demonstrated that the
      classical scheme of fractionation is a valuable indicator of the changes in
      solubility properties which the various polysaccharide components for the wall
      undergo. It does not however yield definite chemical entities. For example, the
      "pectin" fraction contains only about 3% galacturonic acid; the bulk of it being
      composed of glucose, xylose, and galactose. By summation of analysis of these
      various fractions, it was found that substances yielding glucose and xylose upon
      hydrolysis increase with advancing age of the tissue. Galactose- and arabinose
      yielding compounds decrease and mannose appears during maturation. Anhydrouronic
      acids first decrease, then increase. Most interestingly, of the total dry weight
      of the cell wall, only 24, 45, and 50% of the meristematic, elongation, and
      maturation zones respectively are accounted for as simple sugars in the acid
      hydrolysates. Oligosaccharides were not encountered in large amounts so that the
      50 to 75% of the wall weight unaccounted for would consist of polysaccharides or
      oligosaccharides not precipitated by ethanol from the extracting solutions
      employed and by polysaccharides in the hemicellulose fraction which are resistant
      to acid hydrolysis.

PMID- 16656736
TI  - Lengthening versus shortening dark periods and blossoming in sugar cane as
      affected by temperature.
AB  - Sugar cane, an intermediate day plant, clearly received a stronger stimulus to
      flower during lengthening nights than during shortening nights. Flowering was
      vigorous under warm, lengthening nights (21 degrees ) but less so under cool,
      lengthening nights (16-17 degrees ). Warm or cool shortening nights either failed
      to induce flowering altogether or reduced it substantially. Under the warmer
      nights the inductive dark period was 10 hours 57 minutes to 11 hours 26 minutes
      whether the nights were lengthening or shortening. Under cooler conditions, it
      was longer by from 20 minutes to nearly 2 hours.

PMID- 16656737
TI  - Phosphorylation in crested wheatgrass seeds at low water potentials.
AB  - Crested wheatgrass seeds [Agropyron desertorum (Fisch. ex Link) Schult.] were
      tested for their ability to carry on phosphorylation reactions at low water
      potentials. Seeds were treated with (32)P labeled sodium phosphate and incubated
      in air having different controlled relative humidities. Ion exchange
      chromatography and radioassay of phosphate esters indicated that some
      phosphorylation occurred at a water potential of -880 atmospheres. Seeds did not
      incorporate (32)P in nicotinamide adenine dinucleotide, adenosine triphosphate,
      and uridine diphosphate hexose until they were moistened to a water potential of 
      130 atmospheres.

PMID- 16656738
TI  - Protochlorophyllide resynthesis in dark-grown bean leaves.
AB  - The protochlorophyllide content of dark-grown bean leaves was determined at
      various ages. It was detectable the second day after germination and reached a
      maximum on about the tenth day.The resynthesis of protochlorophyllide following a
      single irradiation and the rate of the 685 to 673 mmu shift of the newly formed
      chlorophyll was examined. Leaves up to 5-days old show no lag phase in
      protochlorophyllide resynthesis. By the sixth day, a lag phase is evident which
      increases with age. The rate of the 685 to 673 mmu shift is similarly age
      dependent.

PMID- 16656739
TI  - Studies on Auxin Protectors. IV. The Effect of Manganese on Auxin Protector-I of
      the Japanese Morning Glory.
AB  - Auxin protector-I of the Japanese morning glory is inactivated by manganese.
      Experiments carried out in vitro indicate that in the absence of oxygen the
      manganic, but not the manganous, ion rapidly inactivates the protector. It is
      clear from these, and other data described in this report, and the results of
      other workers, that in the presence of oxygen, manganese accelerates auxin
      inactivation by means of 2 separate and distinct mechanisms: 1) manganese
      catalyzes the oxidation of auxin protectors, and 2) following the inactivation of
      the protectors, or in the absence of protectors, accelerates the oxidation of
      indoleacetic acid by endogenous peroxidases.

PMID- 16656740
TI  - Mediation of a plant response to malformin by ethylene.
AB  - Malformin and ethylene stimulate abscission of the primary leaves of Phaseolus
      aureus Roxb. in the dark, and abscission stimulation by both compounds is
      inhibited by indeleacetic acid and CO(2). Ethylene production by malformin
      treated buds is stimulated within 4 hours. and up to 8 days, after treatment.
      Malformin-induced growth disturbances in P. vulgaris L. and abscission in P.
      aureus are considered mediated by ethylene. Although root curvatures of Zea mays
      L. are induced by both malformin and ethylene, and malformin is inhibited by
      CO(2), ethylene production is not stimulated by malformin. A role of ethylene in
      root curvatures induced by malformin is neither proposed nor disproved.

PMID- 16656741
TI  - Tryptophan Biosynthesis in Cell Cultures of Nicotiana tabacum.
AB  - Some of the general features of the pathway for l-tryptophan biosynthesis in cell
      cultures of Nicotiana tabccum var. Wisc. 38 have been investigated. The results
      of both isotope competition and direct-labeling experiments show that shikimic
      acid, anthranilic acid, indoleglycerol phosphate, and indole can serve as
      precursors to l-tryptophan in these cells, indicating that, in terms of its
      biochemical intermediates, the pathway is similar to that described for the
      bacteria and fungi.

PMID- 16656742
TI  - Stable concentrations of phytochrome in pisum under continuous illumination with
      red light.
AB  - In vivo spectrophotometry showed that the phytochrome concentration in pea
      epicotyl hooks decreased at a constant rate for 4 hours when the tissue was
      exposed to continuous red light. Thereafter the rate slowed progressively so that
      a steady concentration of phytochrome was approached at hour 7. Returning the
      plants to darkness resulted in an increase in phytochrome due to the apparent
      synthesis of P(R). A closely similar pattern of changes was found in the amount
      of phytochrome extracted from the tissue. The establishment of the stable
      concentration was inhibited by 2,4-dichlorophenoxyacetic acid and did not occur
      in segments which had been incubated for longer than 24 hours, but was observed
      when segment growth was inhibited by mannitol. The results may be explained by an
      equilibrium between P(FR) destruction and apparent P(R) synthesis.

PMID- 16656743
TI  - Regulation of Cold Hardiness in Acer negundo.
AB  - The application of gibberellin to Acer negundo either during or after a short
      photoperiod strikingly lowered the amount of hardiness obtained after 4 weeks in
      darkness at 5 degrees . Two growth retardants, B9 and Amo 1618, the latter of
      which interferes with gibberellin synthesis, brought about hardiness increases
      under long photoperiods. The naturally occurring inhibitor, dormin, also
      increased hardiness under the usual inhibiting influence of long photo-periods.
      Extracts from plants given long or short days had gibberellin-like compounds in
      largest quantities during LD and lowest quantities under SD, while the inverse
      was true for the inhibitor.

PMID- 16656744
TI  - Phytochemical Studies on the Tobacco Alkaloids. XII. Identification of gamma
      Methylaminobutyraldehyde and its Precursor Role in Nicotine Biosynthesis.
AB  - gamma-Methylaminobutyraldehyde (N-methylpyrroline) labeled with (14)C was
      isolated from tobacco roots which had metabolized ornithine-2-(14)C. It was
      labeled most strongly 4 hours after adding ornithine-2-(14)C to the root, also
      labeled by putrescine-1,4-(14)C and methionine-(14)CH(3), and observed in the
      root but not in the aerial portions of tobacco plants. gamma-Methyl
      aminobutyraldehyde when added back to the root was an efficient precursor of
      nicotine. Identity of gamma-methylaminobutyraldehyde from tobacco roots was
      confirmed by comparison with the authentic compound.The existence of gamma
      methylaminobutyraldehyde (N-methylpyrroline) in the biosynthetic pathway of
      nicotine indicates that the methyl group must be introduced before condensation
      of the pyridine moiety with the pyrrolidine moiety.

PMID- 16656745
TI  - Respiration of oranges and grapefruits harvested at different stages of
      development.
AB  - Young and unripe oranges and grapefruits stored at 15 degrees or 20 degrees
      evidenced shortly after harvest a marked increase in respiratory rate, and then a
      well-defined maximum which was followed by a decrease.Ethylene production by
      oranges (measured by the manometric method) was observed, with curves parallel to
      the respiratory curves.The respiratory upsurge was accompanied by color changes
      typical of maturity in the above fruits, and by abscission of stem-ends.When
      fruit was harvested close to or at commercial maturity, it evidenced a gradual
      respiration decrease without any upsurge. No ethylene production was detected in
      oranges of this stage.

PMID- 16656746
TI  - Effect of ozone on swelling of tobacco mitochondria.
AB  - The swelling of mitochondria isolated from leaves, roots, and callus tissues of
      Nicotiana tabacum, L, var. White Gold, was measured by following changes in
      optical density at 520 mmu in buffered 0.25 m sucrose or 0.125 m KCl. Ozone
      induced rapid swelling of the isolated mitochondria and increased the
      permeability of mitochondrial membranes. The extent of mitochondrial swelling and
      the amount of soluble proteins and other substances absorbing at 260 and 280 mmu
      released from mitochondria into the suspending medium were positively correlated
      with the length of exposure to O(3). The correlation between the extent of
      mitochondrial swelling and the loss of intramitochondrial materials was also
      highly significant.Protocatechuic acid, when initially present in the suspending
      medium, completely prevented O(3)-induced swelling. Reduced glutathione,
      ascorbate, and l-cysteine partially prevented O(3)-induced swelling. But these
      reducing substances failed to reverse mitochondrial swelling when added after
      O(3) treatment.Polyvinylpyrrolidone (PVP) and bovine serum albumin (BSA) induced
      contraction of tobacco mitochondria in the absence of O(3), but did not reverse
      swelling of O(3)-treated mitochondria. PVP and BSA only stopped O(3)-induced
      swelling. Evidently O(3)-induced swelling was osmotically irreversible.
      Hypertonic solutions of sucrose neither induced contraction of tobacco
      mitochondria nor prevented O(3)-induced swelling.Contraction of tobacco
      mitochondria occurred rapidly at acid pH, but the contracting state affected by
      acid pH did not protect mitochondria from O(3)-induced swelling. Although O(3)
      induced greater swelling at acid pH, the O(3)-treated mitochondria were still
      responsive to acid-induced contraction.

PMID- 16656747
TI  - Studies on the role of RNA synthesis in auxin induction of cell enlargement.
AB  - Selective inhibitors were used to study the connection between nucleic acid
      synthesis and indoleacetic acid (IAA) induction of cell enlargement. Actinomycin
      D (act D) and azaguanine (azaG) almost completely inhibit IAA-induced growth in
      aged artichoke tuber disks when they are added simultaneously with IAA. In
      contrast, when they are added 24 hours after the hormone, these inhibitors have
      little or no effect on the induced growth which continues for 48 hours or more
      with little or no inhibition. Inhibitors of protein synthesis still stop growth
      when applied 24 hours after the IAA, thus protein synthesis and presumably
      supporting metabolism are still essential.In corn coleoptile sections auxin
      induced growth did not show any pronounced tendency to become less sensitive to
      act D as the IAA treatment progressed. Act D did not completely inhibit the
      response to IAA unless the sections were pretreated with act D for 6 hours. In
      contrast to act D, cordycepin produced almost complete inhibition of IAA-induced
      growth when added with the IAA.Although IAA has a very large and very rapid
      stimulatory effect (within 10 min) on incorporation of (32)P-orthophosphate into
      RNA in disks, it did not cause a detectable change in the base composition of the
      RNA synthesized. Furthermore, the promotive effect could be accounted for through
      increased uptake of the (32)P. That much of the RNA synthesis in these tissues is
      not necessary for auxin action is indicated by the results with fluorouracil
      (FU). FU strongly inhibits RNA synthesis, probably acting preferentially on
      ribosomal RNA synthesis, without inhibiting auxin-induced growth in the disks or
      coleoptile sections. FU also strongly inhibited respiration in auxin-treated
      disks indicating that the large promotion of respiration by auxin likewise may
      not be entirely necessary for growth.At least in the artichoke disks, RNA
      synthesis is required for auxin induction of cell enlargement and not for cell
      enlargement itself.The possible relationships of auxin induction of cell
      enlargement and RNA synthesis are discussed.

PMID- 16656748
TI  - The Role of Light in Cold Acclimation of Hedera helix L. var. Thorndale.
AB  - The role of light in cold acclimation of Hedera helix L. var. Thorndale appears
      to differ from that reported for winter annuals. Although light greatly enhances
      the degree of hardiness attained, cold acclimation is not obligatorily linked to
      a light requirement. Photoperiods, varying from 8 to 24 hours, received during
      the cold acclimation period were equally effective in promoting maximum
      hardiness. Relatively low light intensities and short photoperiods stimulated
      maximum hardiness, and proportional increases in hardiness in response to
      increased photoperiods were demonstrated only in stems of prestarved plants.
      Exclusion of CO(2) and high concentrations of photosynthetic inhibitors decreased
      hardiness, but in no instance was hardiness reduced to the level of the dark
      control. The data are only compatible with a photosynthetic role of light if it
      is assumed that only a small portion of the total photosynthates are required to
      elicit maximum hardiness. Alternatively, the light stimulation which was elicited
      by low light intensities, short photoperiods, in the absence of CO(2), and in the
      presence of photosynthetic inhibitors, may be a light signal similar to a
      phytochrome response.

PMID- 16656749
TI  - Effect of Low-intensity Red and Far-red Light and High-intensity White Light on
      the Flowering Response of the Long-day Plant Lemna gibba G3.
AB  - The long-day plant Lemna gibba L., strain G3 exhibits a relatively low
      sensitivity to short, white-light interruptions given during the dark period of a
      short-day cycle. However, the plants are fairly sensitive to low-intensity red
      light treatments given during a 15-hour dark period on the third day of a 2LD
      (9L:15D)-2LD-7SD schedule. Far-red light is almost as effective as red light, and
      attempts to reverse the red light response with subsequent far-red light
      treatments have not been successful. Blue light proved to be without effect. When
      plants were grown on a 48-hour cycle with 15 minutes of red light every 4 hours
      during the dark period, the critical daylength was reduced from about 32 hours to
      slightly less than 12 hours.Continuous red light induced a fairly good flowering
      response. However, as little as 1 hour of white light each day gave a significant
      improvement in the flowering response over that of the continuous red light
      control. White light of 600 to 700 ft-c was more effective than white light of 60
      to 70 ft-c. The white light was much more effective when divided into 2 equal
      exposures given 8 to 12 hours apart. These results suggest an increase in light
      sensitivity with regard to flower induction about 8 to 10 hours after the start
      of the light period.

PMID- 16656750
TI  - Inhibition of the formation of photosynthetic enzymes by inhibitors of
      photosynthesis.
AB  - It has been shown previously that an increase in ribulose diphosphate carboxylase
      activity occurs upon brief illumination of leaves of dark-grown Zea mays plants;
      an increase in ribose 5-phosphate isomerase occurs after prolonged illumination.
      Both of these responses to illumination are inhibited by chloramphenicol.The
      administration of p-chlorophenyldimethylurea, an inhibitor of photosynthesis, to
      etiolated maize does not affect the normal early rise in ribulose diphosphate
      carboxylase activity when the leaves are illuminated but does block the increase
      in ribose 5-phosphate isomerase. This pattern of response suggests that
      photosynthetic activity is required for the increase in isomerase-perhaps
      products of photosynthesis induce isomerase synthesis-but that the level of
      ribulose diphosphate carboxylase is controlled by other processes. Chlorophyll
      formation (as has been shown by others) is slightly suppressed by the inhibitor;
      levels of total soluble leaf protein appear to be unaffected.Salicylaldoxime,
      which is a more general inhibitor of metabolism than p-chlorophenyldimethylurea,
      arrests the normally observed increases of ribulose diphosphate carboxylase,
      ribose 5-phosphate isomerase, and chlorophyll during illumination of dark-grown
      maize. The level of soluble leaf protein is also lower in leaves treated with
      this compound.

PMID- 16656751
TI  - Photocontrol of Spirodela intermedia flavonoids.
AB  - Clone 115 of Spirodela intermedia W. Koch grown in Hutner's medium with sucrose
      produces the glycoflavones vitexin and orientin in darkness or in light of
      various wavelengths. The anthocyanin cyanidin-3-monoglucoside was present only
      after prolonged illumination of the plants with white or blue light. No cyanidin
      glucoside was formed under constant red light. The substitution of red, blue, or
      far-red light for the last 24 hours of culture under constant white light reduced
      each flavonoid over those maintained in white light or given 24 hours of
      darkness. Reducing the light intensity from 900 to 400 ft-c of constant cool
      white fluorescent light had no appreciable influence on vitexin (4'-hydroxyl) but
      markedly reduced orientin and cyanidin-glucoside (both 3'4'-hydroxyl).
      Substituting alternate 12-hour periods of light and darkness for continuous light
      reduced the glycoflavones approximately 50% while cyanidin-glucoside was reduced
      about 85%. Most responses to red, blue, or far-red light are consistent with a
      phytochrome-controlled promotion of vitexin synthesis.The evidence suggests that
      in S. intermedia: A) Environmental conditions which elicit cyanidin-glucoside and
      glycoflavone synthesis are different since a prolonged illumination with white
      light is required for the former but not the latter. B) The availability of a
      3'4'-hydroxyl precursor for orientin and anthocyanin probably limits their
      synthesis in low intensity light. Since vitexin is essentially unaltered under
      these conditions this also suggests that acetate or malonate units for the A-ring
      and the deamination products of aromatic amino acids for the B-ring and carbons
      of the C-ring are not limiting factors. C) Light controls the biosynthesis of
      flavonols in the same manner as glycoflavones; under all experimental conditions
      the synthesis of kaempferol paralleled vitexin while quercetin responded in the
      same manner as crientin.

PMID- 16656752
TI  - Fixation of carbon dioxide in the dark by the malic enzyme of bean and oat stem
      rust uredospores.
AB  - Malic enzyme was found in both bean rust and cat stem rust uredospores. In bean
      rust uredospores it was shown to catalyze the formation of pyruvic acid from l
      malic acid and to synthesize malic acid from pyruvic acid and CO(2). The malic
      enzyme from bean rust uredospores was specific for NADP and dependent on
      manganous ions for activity. The specific activity of the bean rust malic enzyme
      in crude extracts of ungerminated uredospores was approximately 6 times greater
      than that found in crude extracts obtained from germinated uredospores. The malic
      enzyme was also found in extracts obtained from healthy and rust-infected bean
      leaves. The specific activity of the enzyme was approximately 2 to 5 times
      greater in partially purified extracts obtained from the infected bean tissue at
      6 days after inoculation. The specific activity of the malic enzyme in crude
      extracts obtained from oat stem rust uredospores was 2 times greater than the
      specific activity of this enzyme in crude extracts obtained from bean rust
      uredospores. Phosphoenolpyruvate carboxylase activity could not be demonstrated
      in crude extracts obtained from the ungerminated uredospores of the bean rust
      fungus.

PMID- 16656753
TI  - Leaf diffusion resistance, illuminance, and transpiration.
AB  - Stepwise increases in fluorescent illuminance, imposed as a single variable in a
      controlled environment, induced progressive stomatal opening in 8 plant species,
      as evidenced by a consistent decrease in leaf diffusion resistance (R(L)),
      ranging from 15 to 70 sec cm(-1) in darkness to about 1 sec cm(-1) at
      approximately 40 kilolux. The minimum R(L) values were the same for the upper and
      the lower epidermis, provided that stomatal density was adequate. Saturation
      illuminance was not achieved in any species; extrapolation indicates that 50
      kilolux would bring about full stomatal opening (R(L) </= 0.1 sec cm(-1)).In 4
      species, reasonable agreement was obtained in a controlled environment between
      transpiration as measured by weight loss and that calculated from determination
      of (a) the difference in water vapor density from leaf to air, (b) the boundary
      layer resistance, and (c) the leaf diffusion resistance. This result confirms the
      physical validity of the resistance measurement procedure.

PMID- 16656754
TI  - Morphogenic responses of debudded tobacco plants to gibberellic Acid and indole-3
      acetic Acid.
AB  - Stem applications of indole-3-acetic acid (IAA) or gibberellic acid (GA) did not
      prevent or alter tumor or teratoma formation in debudded tobacco plants
      (Nicotiana tabacum L., var. One Sucker). The materials produced intense (in case
      of GA) and moderate (in case of IAA) stem proliferations when applied to debudded
      plants but were without effect on intact plants.The results suggest that
      debudding-tumors are probably not related to or a result of an auxin or
      gibberellin deficit and that total debudding has a marked physiological effect on
      the plant. The altered physiological condition of the debudded plant, indicated
      by its responses to IAA and GA, may likely be related to tumor and teratoma
      formation.

PMID- 16656755
TI  - Metabolism of sugars and organic acids in immature grape berries.
AB  - Individual intact excised immature Sultana berries were supplied through the cut
      pedicel with (14)C-sugars and organic acids. When (14)C-hexoses were supplied
      malic and tartaric acids accounted for 25% and 10% of the total activity
      extracted after 24 hours, and sucrose was synthesized. It is proposed that the
      changes in the levels of organic acids during ripening are related to changes in
      the ability of the berry to synthesize them. Although administration of uniformly
      labeled sucrose resulted in the unequal labeling of glucose and fructose, the
      results indicate breakdown of sucrose by invertase. It is suggested that the
      route of entry of the pedicel-fed sugars into the berry may be different from the
      route taken by sugar translocated from the leaf.

PMID- 16656756
TI  - Studies on the ribonucleic Acid from wheat leaves and chloroplasts.
AB  - The chloroplast, leaf ribosomal, and leaf total RNA from seedlings of 2 varieties
      of Triticum durum and 3 varieties of Triticum vulgare were compared. For a given
      RNA preparation the major nucleotide composition was the same for all varieties.
      Irrespective of the variety, the chloroplast total RNA had a higher cytidylic and
      a lower adenylic acid content than the leaf ribosomal RNA, whereas, the guanylic
      and uridylic acid content of all RNA preparations was essentially the same.
      Pseudouridylic acid was present in all RNA preparations and was consistently
      higher in the durum than the vulgare varieties for leaf ribosomal RNA and leaf
      total RNA. The leaf ribosomal RNA of all varieties had 2 sub-units with
      sedimentation coefficients of approximately 18 S and 25 S. The molecular weight
      of the faster sedimenting subunit was about 2 times that of the slower
      sedimenting subunit.

PMID- 16656757
TI  - Oxidized and reduced nicotinamide adenine dinucleotide phosphate levels of plants
      hardened and unhardened against chilling injury.
AB  - Pea plants (Pisum sativum L. var. Alaska) subjected to low temperature (5 degrees
      ) in the light acquired resistance against chilling injury.Unhardened plants
      maintained high NADP and low NADPH levels during illumination at 25 degrees but
      hardened plants had low NADP and high NADPH levels in the light. When the
      unhardened plants were transferred to the dark room at 25 degrees , their NADPH
      levels decreased immediately. On the other hand, hardened plants maintained a
      high NADPH level for a few hours even in the dark.

PMID- 16656758
TI  - Influence of Substrate and Tissue Manganese on the IAA-Oxidase System in Cotton.
AB  - Tissue manganese was found to influence the indoleacetic acid (IAA) system of
      cotton over a wide range of concentrations. The cofactor and inhibitor activities
      of the IAA-oxidase system were affected as the concentration of manganese in the
      tissue was varied. Maximum inhibitor activity was found in leaf extracts from the
      plants grown in 0.5 mg/l manganese (Hoagland's level). The inhibitor activity
      decreased in the leaf extracts of plants grown at concentrations of manganese
      either higher or lower than 0.5 mg/l. Abnormally high IAA-oxidase activity was
      found in the leaves of plants grown in deficient levels of manganese (<0.0005,
      0.005 mg/l) and the extracts from plants in the <0.0005 mg/l Mn treatment showed
      IAA-oxidase cofactor activity.

PMID- 16656759
TI  - Properties of succinate oxidation in tomato fruit mitochondria.
AB  - Mitochondria from tomato fruit (Lycopersicon esculentum Mill.) exhibited a
      respiratory control ratio of 2.5 and an ADP:O ratio of 1.3 for succinate
      oxidation for 24 hours after isolation. They also showed a delay in response to
      the first addition of ADP. The addition of ATP and ADP before succinate
      eliminated the delayed response as did chelation of endogenous cations with
      ethylenediaminetetraacetic acid. The addition of ATP after succinate resulted in
      a longer delay in response than that obtained with ADP. Exogenous oxaloacetate in
      low concentration inhibited respiration in states 3 and 4 with succinate and
      resulted in delayed response to ADP. The function of adenine nucleotide during
      the delay in response may be to promote the metabolism of oxaloacetate or to
      decrease the affinity of oxaloacetate to its site of inhibition.

PMID- 16656760
TI  - The effect soaking pea seeds with or without seedcoats has on seedling growth.
AB  - Pea seeds (Pisum sativum L. ;Alaska') with intact seedcoats (WC) and with
      seedcoats removed (WOC) were soaked in distilled water for 24 hours at 20 degrees
      . The water, containing the pea diffusate, was decanted after the second, fourth,
      sixth, eighth, twelfth, and twenty-fourth hour and analyzed for total nitrogen,
      alpha-amino nitrogen, carbohydrate, and total solute dry weight. The seeds were
      germinated at 20 degrees in a 16 hour photoperiod of 300 foot candles. Stem
      lengths and dry weights of roots, shoots and cotyledons were determined after 4,
      11, and 18 days of growth. WOC seeds imbibed more water than WC seeds during the
      24 hour imbibition period. Diffusates from WOC seeds always contained more solute
      than diffusates from WC seeds. Maltose, glucose, and fructose were not detected
      in the early diffusates from WOC seeds but were found in WC seed diffusates at
      all times. Seedlings from WC seeds had longer stems than those from WOC seeds.
      The dry weight of stems and roots of WC seedlings was greater than those from WOC
      seedlings. The dry weight of cotyledons from 18 day-old WC seedlings was less
      than from WOC seedlings. Water absorption by WC seeds was slower than by WOC
      seeds. Removal of the seedcoat allowed rapid imbibition resulting in seed injury
      presumably because of the loss of solutes which included monosaccharides,
      disaccharides, amino acids, and other nitrogen containing compounds. These
      results are consistent with the hypothesis that rapid imbibition disrupts
      membrane organization leading to reduction of seedling growth.

PMID- 16656761
TI  - Changes in Enzyme Levels During Germination of Seeds of Triticum durum.
AB  - The changes in level of activity during the germination of wheat seedling
      (Triticum durum) in the dark have been investigated with 4 enzymes of glycolysis,
      2 enzymes of the pentose phosphate shunt, 2 of the tricarboxylic acid cycle, 2 of
      amino acid metabolism and acid phosphatase. For some enzymes, which function in
      photosynthesis (fructose diphosphate aldolase, glyceraldehyde phosphate
      dehydrogenase NADP dependent), the level of activity was influenced by the
      presence of light.

PMID- 16656762
TI  - Effect of trifluralin on growth, morphology, and nucleic Acid synthesis.
AB  - Roots and shoots of corn seedlings (Zea mays L. var. Dixie 18) germinated in
      trifluralin (alpha,alpha,alpha-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine)
      solutions are characterized by radial enlargement of the cortical cells and by
      multinucleate cells in the meristematic regions. Trifluralin inhibits elongation
      of Avena coleoptile sections at concentrations of 0.1 mum to 10 mum. Synthesis of
      DNA, RNA, and protein is suppressed in the root tips while no significant effect
      is noticeable in the shoots of corn germinated in trifluralin. A (32)P time
      course study of 48, 72, and 96 hours utilizing phenol extraction and MAK column
      separation of corn root and shoot nucleic acids showed suppression of (32)P
      incorporation in the treated roots; however, the 72 and 96 hour treated shoots
      incorporated a much greater amount than the control with most of the increased
      incorporation found in the sRNA and DNA fractions. The increased activity in the
      DNA may be due to a high G-C type DNA. No selective suppression or enhancement of
      any particular RNA species was noticed in the treated plants.

PMID- 16656763
TI  - Further evidence of oxygen diffusion as the determining factor in the relation
      between disk thickness and respiration of potato tissue.
AB  - The effect of oxygen tension above atmospheric pO(2) on the development of
      respiratory capacity in potato disks has been examined. Raising the oxygen
      tension of the aqueous environment to 40% during the aging of 2.0 mm or 3.0 mm
      thick disks at 25 degrees progressively increased the respiration rate of the
      tissue as shown by subsequent assay in 100% oxygen. Disks 3.0 mm thick showed a
      greater response to increased pO(2) than did 2.0 mm disks. A comparison of center
      1.0 mm sections excised from 3.0 mm disks after aging, showed that the
      respiration rate of internal tissue from disks aged in high pO(2) was
      approximately 40% greater than such tissue aged with atmospheric pO(2). The
      characteristic inverse relationship between respiration rate and thickness in
      aged disks can be modified from a concave-downwards curve to a convex-downwards
      curve by pretreating the tissue with increased pO(2), thus indicating that
      raising the pO(2) during aging can increase the thickness threshold at which the
      transition from tissue manifesting the respiratory characteristics of thin disks
      to that manifesting the characteristics of thick disks, occurs. Similarly
      increased pO(2) during aging can modify the hyperbolic relationship obtaining
      between pretreatment temperature in the range 10 degrees to 25 degrees and
      respiratory capacity of aged 3.0 mm disks, to approximate to the linear
      relationship observed with 0.75 mm disks. It is concluded that the development of
      respiratory capacity in disks between 0.75 mm and 3.0 mm thick is restricted by
      oxygen dificiency and that the characteristic inverse relationship between
      respiration rate and thickness in aged disks is largely attributable to this
      factor, the influence of which is discernible both on the development of
      respiratory capacity and on its subsequent assay.

PMID- 16656764
TI  - Water relations of pine seedlings in relation to root and shoot growth.
AB  - The effects of water stress on growth and water relations of loblolly and white
      pine seedlings were studied during series of drying cycles. As mean soil water
      potential decreased, growth of roots, needles, and buds decreased. Growth of
      roots during successive severe drying cycles was not uniform, however. A study of
      needle and root extension showed that of the total growth of roots for 3 7-day
      drying cycles, only 6% occurred during the third cycle, while needle extension
      was uniform for the 3 cycles. The difference in response of needles and roots to
      drying cycles may be attributed primarily to the effect of water stress on the
      growing region. When subjected to a severe stress, roots matured toward the tip
      and became dormant, resulting in less growth during subsequent drying cycles. The
      intercalary growing region of needles, however, was not altered seriously enough
      by the stress to cause a difference in amount of growth during each drying
      cycle.Transpiration of loblolly pine was lower in the second drying cycle than in
      the first. Needle water potential after rewatering was as high as that of control
      plants watered daily; root resistance was apparently not important in restricting
      transpiration during a second drying cycle. Needle diffusion resistance of
      loblolly pine, measured with a low-resistance diffusion porometer, was slightly
      higher during the second drying cycle than during the first. In addition, many
      primary needles were killed during the first period of stress. These factors
      contributed to the reduction of transpiration during the second drying cycle.
      Diffusion resistance of Coleus increased and transpiration ceased during the
      first drying cycle while water potential remained relatively high. After
      rewatering, both leaf resistance and transpiration returned to the control level,
      presumably because the stress during the first period of drying was not severe.
      The diffusion resistances observed for well-watered plants were 30 to 50 sec.cm(
      1) for loblolly pine, 3 to 5 sec.cm(-1) for Coleus, and 4 to 6 sec.cm(-1) for
      tomato. These values agree closely with those reported by other workers.

PMID- 16656765
TI  - Glycolate oxidase activity in algae.

PMID- 16656766
TI  - Relationships between the development of adventitious roots and the biosynthesis
      of anthocyanins in first internodes of sorghum.
AB  - The initiation and subsequent growth of adventitious roots in excised first
      internodes of Sorghum vulgare var. Wheatland milo were studied to determine the
      effect of these processes on anthocyanin biosyntheses. Segmentation of the
      internodes inhibited both adventitious root growth and accumulation of cyanidin
      equally in all segments; these results can be interpreted as a common requirement
      for bidirectional longitudinal transport. The presence of the coleoptile,
      especially in the absence of the base of the internode, inhibited the growth of
      the roots, but increased the number of root initials. High intensities of white
      and blue light which induced cyanidin synthesis slightly decreased adventitious
      root growth. Anaerobic conditions produced by solution infiltration strongly
      inhibited the growth of adventitious roots and greatly increased the accumulation
      of apigeninidin and luteolinidin. Addition of indoleacetic acid, kinetin and
      cofactors such as pyridoxine produced effects on the initiation and subsequent
      growth of these roots similar to those effects reported in the literature. But
      unlike root formation in hypocotyls, the initiation of adventitious roots in
      Sorghum internodes was not always directly correlated with the accumulation of
      anthocyanins, and the subsequent growth of these roots was frequently inversely
      correlated with some of the anthocyanin biosyntheses. The possible nature of
      these correlations is discussed. Comparisons are made with related Sorghum lines
      and mutants.

PMID- 16656767
TI  - Gibberellin-like Activity in Berries of Seeded and Seedless Tokay Grapes.
AB  - Gibberellin-like activity in berries of both ;Tokay' (seeded) and ;Seedless
      Tokay' grapes (Vitis vinifera L.) at different stages of development was
      determined. Activity in both seeded and seedless berries was mainly in the acidic
      ethyl acetate fraction. In seeded berries there was very high activity beginning
      at the early fruit-set stage and persisting for about 3 weeks after which the
      activity fell to low level and vanished by the middle of July. On August 1 there
      was another activity peak. The activity in ;Seedless Tokay' was similar except
      the decline was considerably more rapid and a secondary peak was reached in mid
      June instead of August. The gibberellin-like substances in the acidic ethyl
      acetate fraction occurred mainly between R(F) 0.3 and 0.6 when the chromatogram
      was developed with ammoniacal isopropanol.The gibberellin-like substances from
      both types of berries were active in dwarf pea, dwarf corn, and lettuce hypocotyl
      bioassays, but not in the cucumber hypocotyl test. The role of gibberellin-like
      substances in berry development is discussed.

PMID- 16656768
TI  - Thresholds for georesponse to acceleration in gravity-compensated Avena
      seedlings.
AB  - The magnitude of acceleration required to induce growth responses in Avena
      seedlings grown in the absence of tropic response to earth gravity has been
      investigated. For this purpose, a clinostat was developed that imposes
      accelerations from about 10(-9) g to 3 g upon the seedling; simultaneously, it
      nullifies, or compensates for, response to the directional component of the
      gravitational-force vector by rotating the seedling on a horizontal axis. When
      accelerations less than 10(-3) g are applied in either the acropetal or the
      basipetal direction, the growth in length and weight of the various organs is not
      materially different from that of compensated seedlings to which no longitudinal
      force is applied. At accelerations between 10(-3) and 10(-2) g, differences in
      growth become highly significant. When the centrifugal forces are transverse to
      the seedling during compensation, the threshold acceleration range for
      geoperception, as manifest by shoot reorientation, is again between 10(-3) and
      10(-2) g. Geotropic reorientation of the root becomes apparent after exposures
      between 10(-4) and 10(-3) g.

PMID- 16656769
TI  - Inhibition of water uptake in sugar beet roots by ammonia.
AB  - Ammonium sulfate, ammonium carbonate or ammonia gas inhibited water uptake in
      sugar beet roots whenever the pH was sufficiently high to cause the production of
      ammonia. When ammonia was removed by aeration, inhibition of the water uptake by
      roots was rapidly reversed. ATP at 0.2 mm appeared to either wholly or partially
      prevent the ammonia-induced inhibition of water uptake by roots. ATP may be
      involved in maintaining the structure of water pathways through the root. In
      roots lacking epidermis, ammonia did not inhibit water uptake by the roots. This
      may indicate that the site of the inhibition lies within the root epidermis.

PMID- 16656770
TI  - Interactions of indoleacetic Acid and gibberellic Acid in leaf abscission
      control.
AB  - Debladed midribs of citrus leaves showed the typical delay of abscission in
      response to indoleacetic acid (IAA), and the typical acceleration of abscission
      in response to gibberellic acid (GA). Interaction experiments with these 2
      hormones indicated that the balance of the 2 hormones may be more important in
      regulating abscission than the quantity of either. The often reported
      acceleration of abscission with low quantities of IAA did not seem to exist in
      citrus. IAA did accelerate abscission in this tissue when its application was
      delayed for at least 24 hours after deblading, which suggests the 2-stage effect
      is also present in citrus.When abscission was first delayed with IAA and then
      allowed to continue, the rate of abscission proceeded at a slower rate than was
      typical for this tissue. This slower rate was also typical of the effect observed
      when GA overcame the abscission retarding effect of IAA. The phenylurethane,
      Barban, blocked the GA acceleration of abscission, but it did not affect the rate
      of abscission of control or IAA treated midribs.

PMID- 16656771
TI  - Protein synthesis in abscission: the distinctiveness of the abscission zone and
      its response to gibberellic Acid and indoleacetic Acid.
AB  - Abscission zone tissue of citrus was shown to have a higher rate of protein
      synthesis than tissue distal or proximal to it, based on the incorporation of
      leucine-1-(14)C. The proximal tissue had the slowest rate of protein synthesis.
      As the tissue approached abscission, the rate of synthesis in the abscission zone
      decreased and the differences in rate of protein synthesis between the 3 zones
      almost disappeared. IAA, which delayed abscission, maintained the protein
      synthesis gradient between the abscission and proximal zones, but the distal zone
      tissue was as active in protein synthesis as the abscission zone. Differences in
      uptake of the leucine were also observed between different zones and treatments.
      Regardless of the tissue or the treatment, there was a sharp increase in uptake
      at the 24 hour point.Direct incubation of abscission zones in IAA and gibberellic
      acid (GA) indicated that the action of gibberellic acid on abscission is probably
      through a stimulation of protein synthesis, while IAA seems to act by maintaining
      the existing rate of protein synthesis in the cells of the abscission zone.

PMID- 16656772
TI  - Sequential Induction of Phenylalanine Ammonia-lyase and a Lyase-inactivating
      System in Potato Tuber Disks.
AB  - The light induced synthesis of phenylalanine ammonia-lyase in disks cut from
      potato tubers is very sensitive to cycloheximide. Synthesis is inhibited 50% in
      disks cultured on 5 mum cycloheximide instead of water and almost completely in
      disks aged in the presence of 10 mum inhibitor. Inhibition is irreversible. Fresh
      disks exposed only 1 hour to 10 mum cycloheximide do not synthesize enzyme during
      the subsequent 24 hours.Normally a maximal enzyme activity develops in disks
      about 24 hours after being cut from the tuber. Thereafter enzyme activity
      declines. The disappearance of enzyme is not affected by concentrations of
      cycloheximide sufficient to inhibit the synthesis of enzyme initially. No
      disappearance of enzyme is noted during the initial phase of induction if enzyme
      synthesis is inhibited by cycloheximide. However, enzyme does disappear from the
      tissue if more than half the maximal enzyme content is allowed to form before
      synthesis is inhibited. If cycloheximide at a concentration 10-fold that needed
      to inhibit synthesis completely is added to disks after they have attained a
      maximal enzyme level, then subsequent loss of enzyme activity from the tissue is
      prevented. The initial stability of the enzyme in the absence of further
      synthesis and the inhibition of enzyme disappearance by high concentrations of
      cycloheximide suggest A) that early phases of induction involve synthesis of
      enzyme protein in the absence of turnover, B) that a system capable of degrading
      or inactivating the lyase subsequently forms in the tissue, and C) that the
      formation of the degrading or inactivating system requires protein synthesis.The
      effect of cycloheximide on uptake and incorporation of l-isoleucine-U-(14)C into
      soluble and insoluble proteins of tuber disks was also examined. During induction
      the rate of uptake increased 3 to 4-fold, and the rate of incorporation into
      protein, corrected for change in uptake, increased 25-fold. Cycloheximide
      inhibited incorporation of isoleucine-(14)C into proteins of fresh disks more
      than 80%. It did not prevent activation of general protein synthesis during
      induction and inhibited incorporation in induced disks only 20%. At all times
      incorporation of amino acid into the soluble, lyase-rich, protein fraction was
      more sensitive to cycloheximide than the insoluble fraction.

PMID- 16656773
TI  - Further evidence for an elongation-decarboxylation mechanism in the biosynthesis
      of paraffins in leaves.
AB  - In isolated tobacco leaves l-valine-U-(14)C gave rise to labeled even-numbered
      isobranched fatty acids containing 16 to 26 carbon atoms and iso C(29), iso
      C(31), and iso C(33) paraffins. l-Isoleucine-U-(14)C on the other hand produced
      labeled odd-numbered anteiso C(17) to C(27) fatty acids and anteiso C(30) and
      C(32) paraffins. Trichloroacetic acid inhibited the incorporation of isobutyrate
      into C(20) and higher fatty acids and paraffins without affecting the synthesis
      of the C(16) and C(18) fatty acids. Thus the very long branched fatty acids are
      biosynthetically related to the paraffins. In Senecio odoris leaves acetate-1
      (14)C was incorporated into the paraffins (mainly n-C(31)) only in the epidermis
      although acetate was readily incorporated into fatty acids in the mesophyll
      tissue. Similarly only the epidermal tissue incorporated acetate into fatty acids
      longer than C(18) suggesting that the epidermis is the site of synthesis of both
      paraffins and the very long fatty acids. In broccoli leaves n-C(12) acid labeled
      with (14)C in the carboxyl carbon and (3)H in the methylene carbons was
      incorporated into C(29) paraffin without the loss of (14)C relative to (3)H.
      Since n-C(18) acid is known to be incorporated into the paraffin without loss of
      carboxyl carbon these results suggest that the condensation of C(12) acid with
      C(18) acid is not responsible for n-C(29) paraffin synthesis in this tissue. Thus
      all the experimental evidence thus far obtained strongly suggests that elongation
      of fatty acids followed by decarboxylation is the most likely pathway for
      paraffin biosynthesis in leaves.

PMID- 16656774
TI  - Relationship of boron to gibberellic Acid-induced proliferation in debudded
      tobacco plants.
AB  - Stem applications of gibberellic acid (GA) to debudded tobacco plants (Nicotiona
      tabacum L., var. One Sucker) produce stem swellings that involve intense
      proliferation of, primarily, xylem tissue. Withholding boron from GA-treated
      debudded plants greatly reduces the GA-induced proliferation. This response
      offers a system for directly demonstrating the effect of boron on xylem formation
      and lignification that is unconfounded by the effect of boron on elongation
      growth.

PMID- 16656775
TI  - Influence of light intensity at different temperatures on rate of respiration of
      douglas-fir seedlings.
AB  - The rate of photorespiration of Douglas-fir seedlings was measured under
      different light intensities by: (1) extrapolating the curve for CO(2) uptake in
      relation to atmospheric CO(2) content to zero CO(2) content, and (2) measuring
      CO(2) evolution of the plants into a CO(2)-free airstream. Different results,
      obtained from these techniques, were believed to be caused by a severe
      restriction of the photosynthetic activity when the latter was used. With the
      first method, CO(2) evolution was lower than the dark respiration rate at low
      light intensity. For all temperatures studied (6 degrees , 20 degrees , 28
      degrees ) a further increase in light intensity raised the CO(2) evolution above
      dark respiration before it leveled off. The rate of CO(2) evolution was
      stimulated by increase in temperature at all light intensities. With the CO(2)
      free air method, CO(2) evolution in the light was less than dark respiration at
      all light intensities.

PMID- 16656776
TI  - Kinetics and Energetics of Light-enhanced Potassium Absorption by Corn Leaf
      Tissue.
AB  - The effect of illumination on the absorption of K(+) by leaf tissue of Zea mays
      was investigated. The rate of K(+) absorption was enhanced by exposure of slices
      of corn leaf tissue to light, even of relatively low intensities. Potassium was
      transported inward, with virtually no efflux of previously accumulated K(+). The
      evidence indicates that the transport mechanism for absorption of K(+) is the
      same in the light as in the dark, but that the source of energy for absorption of
      K(+) is different in the light from that in the dark. Various anti-metabolites
      were used to establish that the energy utilized for active ion transport in the
      light came partly from ATP supplied by cyclic photophosphorylation. Expenditure
      of ATP was required in the dark too, but this ATP was formed by oxidative
      phosphorylation. Establishing the ultimate source of energy for active ion uptake
      by higher plants might be facilitated by demonstration of an ion-transport
      process that is not linked directly with the transfer of electrons in the
      mitochondrial cytochrome chain.

PMID- 16656777
TI  - Aspects of the Drought Tolerance in Creosotebush (Larrea divaricata).
AB  - In order to understand better the physiological adaption of creosotebush (Larrea
      divaricata Cav.) to drought conditions, its carbohydrate and nitrogen metabolism
      after a 7-day desiccation period under controlled conditions were studied.
      Although fructose was not significantly altered in the leaves of desiccated
      plants, as compared to those maintained under normal moisture conditions, both
      glucose and sucrose were significantly reduced. Total amino acids more than
      doubled under moisture stress, the increase being predominantly due to proline,
      phenylalanine, and glutamic acid. Significant increases also occurred in alanine,
      arginine, histidine, isoleucine, and valine. Increases or decreases in other
      amino acids were not significant. These stress-induced changes in certain amino
      acids are considered in relationship to protein hydrolysis, to accumulation of
      nitrogen degradation products translocated from the roots, and to the possible
      function of specific amino acids (e.g., proline) in NH(3) (+) storage.

PMID- 16656778
TI  - Template requirement of maize RNA polymerase.
AB  - Maize RNA polymerase utilizes heated deoxyribonucleic acid more effectively than
      native deoxyribonucleic acid as a template for ribonucleic acid synthesis. A
      ribonucleic acid-deoxyribonucleic acid hybrid accumulates in the presence of
      heated deoxyribonucleic acid. The amount of product formed with either native or
      heat-denatured deoxyribonucleic acid does not exceed the amount of
      deoxyribonucleic acid added as template.

PMID- 16656779
TI  - Dimethyl sulfoxide: reversible inhibitor of pollen tube growth.
AB  - Five percent dimethyl sulfoxide (DMSO) completely inhibited tube initiation,
      stopped tube growth and suppressed the high respiration associated with tube
      growth of lily pollen. The effect of DMSO on respiration was indirect because
      uncoupling concentrations of 2,4-dinitrophenol abolished the inhibition of
      respiration. Five percent DMSO did not inhibit rapid starch synthesis during the
      first 30 minutes of incubation, nor did DMSO inhibit the period of high
      respiration associated with rapid starch synthesis. DMSO did not cause permanent
      damage to the cells since normal pollen tube growth occurred after its removal.
      Dimethyl sulfoxide is not a general inhibitor of pollen metabolism, but it may be
      a specific inhibitor of a process required for tube growth.

PMID- 16656780
TI  - Fatty Acid composition in tobacco I. Green tobacco plants.
AB  - The major fatty acids (16 and 18 carbons) in leaves, flowers, and seeds of
      Nicotiana tabacum L. cv. Catterton have been analyzed at various intervals during
      the growth period. From the pattern of their accumulation and relative
      distribution, it was found that A) the amount of fatty acids in upper young
      leaves attained a maximum about 75 days after transplanting which is the time of
      early flowering, while in older leaves the fatty acids continuously declined; B)
      the relative amount of linolenic acid (18:3) increased progressively with leaf
      development, from 30% at an early stage to 60% at maturity, while other fatty
      acids (18:2, 18:1, 18:0, and 16:0) decreased during the same period, indicating a
      progressive desaturation; and C) a rapid increase of fatty acids was found as
      flowers developed into seedpods, particularly of linoleic acid (18:2), which
      comprises 75% of tobacco seed oil.Air-curing resulted in a loss of fatty acids,
      especially the unsaturated ones.

PMID- 16656781
TI  - A press for anaerobic disintegration of small amounts of tissue.

PMID- 16656782
TI  - Increased root initiation in pinto bean hypocotyls with 2,4-dinitrophenol.

PMID- 16656783
TI  - Ethylene enhanced release of alpha-amylase from barley aleurone cells.

PMID- 16656784
TI  - Ribosomal RNA nucleotide sequence homologies in plants.

PMID- 16656785
TI  - Occurrence of gibberellin a(3) in parthenocarpic apple fruit.

PMID- 16656786
TI  - Cytokinins in tRNA of Corynebacterium fascians.

PMID- 16656787
TI  - Mechanism of Enhancement of IAA Oxidation by 2,4-Dichlorophenol.

PMID- 16656788
TI  - On the light requirement for betalain biogenesis.

PMID- 16656789
TI  - Vein loading and transport in detached leaves.

PMID- 16656790
TI  - Effect of Oxygen on the Rates of CO(2) Evolution in Light and in Darkness by
      Photosynthesizing and Non-Photosynthesizing Leaves.

PMID- 16656791
TI  - Effects of Abscisin II on Phenylalanine Ammonia-Lyase Activity in Excised Bean
      Axes.

PMID- 16656792
TI  - Beta gauging leaf water status: influence of changing leaf characteristics.

PMID- 16656793
TI  - Certain effects of benzimidazole on young tobacco plants.

PMID- 16656794
TI  - Gleb krotkov, 1901-1968.

PMID- 16656795
TI  - Decrease in net photosynthesis caused by respiration.
AB  - CO(2) exchange between air and leaf is conceived as a current along a resistor
      with a respiratory current, unaffected by CO(2) concentration, entering the
      resistor. The conclusion follows that a plant placed in an atmosphere free of
      CO(2) will increase the CO(2) concentration to the compensation concentration
      along a curve determined by the resistor and the volume of the atmosphere. This
      was verified. Also a photosynthesis rate calculated from the parameters of the
      observed curve agreed with an independent observation of photosynthesis in CO(2)
      free air. The decrease in net photosynthesis caused by respiration is, according
      to the model, the CO(2) compensation concentration divided by the concentration
      in the atmosphere.

PMID- 16656796
TI  - Effect of sterols on the permeability of alcohol-treated red beet tissue.
AB  - Alcohols and hydrogen peroxide altered the permeability of membranes of Beta
      vulgaris root cells. Generally alcohols increased the permeability of membranes
      without going through an induction period except methanol which required a 10- to
      15-hour induction period. The membrane effect of methanol could be inhibited with
      CaCl(2), cholesterol, beta-sitosterol, and stigmasterol. Cholesterol was the most
      effective inhibitor, followed by beta-sitosterol and stigmasterol; and at the
      same concentration, the sterols were more effective than CaCl(2), the classic
      membrane stabilizer.Ergosterol increased the methanol-initiated betacyanin
      leakage. Since none of the tested sterols reversed the betacyanin efflux induced
      by hydrogen peroxide, the sterols do not apparently act as antioxidants. The
      results are explained in terms of sterol-phospholipid interaction, based on
      stereochemistry and charge distribution.

PMID- 16656797
TI  - Phytochrome and seed germination. V. Changes of phytochrome content during the
      germination of cucumber seeds.
AB  - Cucumber seeds are light-sensitive, dark-germinating seeds. Inhibition of
      germination can be induced by prolonged exposure to continuous or intermittent
      FR. The dark germination process and the response to FR are phytochrome
      controlled. Phytochrome can be detected in these seeds by differential
      spectrophotometry in vivo. Spectrophotometrically measurable phytochrome
      increases during dark germination. The rate of increase is temperature dependent.
      Light treatments which are inhibitory for germination result in phytochrome
      contents lower than those of the seeds germinating in darkness. Treatments which
      restore germination also restore phytochrome formation.

PMID- 16656798
TI  - In vitro Protein Synthesis by Plastids of Phaseolus vulgaris. II. The Probable
      Relation Between Ribonuclease Insensitive Amino Acid Incorporation and the
      Presence of Intact Chloroplasts.
AB  - Amino acid incorporation into protein by chloroplasts from primary leaves of
      Phaseolus vulgaris L., var. Black Valentine is only partially inhibited by 400
      mug/ml ribonuclease. The rate of incorporation, in the presence of ribonuclease,
      is progressively inhibited with time, and ceases after about half an hour.
      Preincubation of chloroplasts at 25 degrees , in the absence of ribonuclease,
      increases the inhibitory effect of ribonuclease on the initial rate of
      incorporation of amino acid into protein. Examination of electron micrographs of
      freshly prepared chloroplast suspensions shows that chloroplasts are largely
      intact. However, after incubation at 25 degrees for 1 hour the chloroplasts are
      disrupted, as indicated by loss of their stroma contents. It is concluded that
      the intact chloroplast membrane is relatively impermeable to ribonuclease. Amino
      acid incorporating activity probably becomes inhibited as the inside of the
      chloroplast is made accessible to ribonuclease by breakage of membranes during
      incubation at 25 degrees .

PMID- 16656799
TI  - In vitro Protein Synthesis by Plastids of Phaseolus vulgaris. III. Formation of
      Lamellar and Soluble Chloroplast Protein.
AB  - Chloroplasts from leaves of plants which had been grown in the dark, and then
      illuminated for 12 hours were isolated, and allowed to incorporate (14)C-leucine
      into protein, and the products of this incorporation were studied. Lamellar and
      soluble proteins are the principal products, and are formed in about equal
      amounts. Only some of the soluble proteins become heavily labeled. Those with
      highest specific activity have a molecular weight of the order of 140,000, while
      the higher molecular weight Fraction I protein has a much lower specific
      activity. The soluble protein as a whole does not serve as a precursor for the
      lamellar protein, and vice-versa, although a precursor-product relationship
      between a minor component of the soluble fraction and the lamellar fraction has
      not been ruled out. The relative protein synthesizing capabilities of
      chloroplasts and mitochondria are discussed with reference to the data presented.

PMID- 16656800
TI  - Photosynthesis and transpiration of monterey pine seedlings as a function of soil
      water suction and soil temperature.
AB  - Rates of photosynthesis, respiration, and transpiration of Monterey pine (Pinus
      radiata D. Don) were measured under controlled conditions of soil water suction
      and soil temperature. Air temperature, relative humidity, light intensity, and
      air movement were maintained constant. Rates of net photosynthesis, respiration,
      and transpiration decreased with increasing soil water suction. The decrease in
      the rates of net photosynthesis and transpiration as a function of the soil
      temperature at low soil water suctions may be attributed to changes in the
      viscosity of water. At soil water suctions larger than 0.70 bars rates of
      transpiration and net photosynthesis may be affected in the same proportion by
      changes in stomatal apertures.

PMID- 16656801
TI  - Estimates of the diffusion resistance of some large sunflower leaves in the
      field.
AB  - Studies were made of resistance to gaseous exchange between large sunflower
      leaves and the bulk air in a crop canopy. Two components of the diffusive pathway
      for mass and sensible heat were evaluated; A) the resistance from the interior of
      the leaf to the leaf surface, and B) the resistance from the surface of the leaf
      through the leaf boundary air layer to the bulk air.IT WAS FOUND THAT: A) leaf
      resistance not only displays diurnal trends but shorter fluctuations, and B)
      boundary air layer resistance was significantly smaller than predicted from
      classical boundary layer formulae.

PMID- 16656802
TI  - Manganese absorption by excised barley roots.
AB  - Short-term absorption studies with 5-day-old excised barley roots revealed that
      the basic aspects of Mn absorption were similar to those of other metabolically
      absorbed cations. Following an initial non-metabolic equilibration with the root,
      Mn was absorbed for several hours at a slower steady-state rate comparable to
      that of other inorganic cations. Complete or nearly complete inhibition of the
      steady-state phase by low temperature, dinitrophenol, and azide provides strong
      evidence that Mn transport into this tissue was metabolically mediated. Within
      limits, the rate of transport was strongly dependent upon the concentrations of
      Mn and the hydrogen ions in the ambient solution. Absorption increased rapidly
      with increasing concentrations of Mn up to 1 meq per liter. Above this
      concentration, the rate leveled off, apparently due to a saturation of the
      transport mechanism. Within the physiological pH range in which Mn is soluble
      (below pH 7), absorption increased greatly with decreasing hydrogen-ion
      concentration.

PMID- 16656803
TI  - Physiological studies on pea tendrils. V. Membrane changes and water movement
      associated with contact coiling.
AB  - The coiling of excised pea tendrils in response to mechanical stimulation is
      accompanied by an increased efflux from their cut bases of electrolytes and label
      from previously absorbed (14)C-acetate and (14)C-sucrose. The major excreted
      cation is H(+); H(+) loss is potentiated by pretreatment with benzoic acid, which
      also leaves the tendrils during coiling.Label from previously absorbed tritiated
      water is excreted during coiling, mainly from the ventral side of the tendril,
      which contracts in the initial phase of coiling. Such label does not pass from
      the ventral to the dorsal side. Similarities between this and other rapidly
      moving systems in plants are surveyed and a hypothesis to explain turgor
      movements is advanced.

PMID- 16656804
TI  - Metabolic fate of 3,4-dichloropropionanilide in plants: the metabolism of the
      propionic Acid moiety.
AB  - 3,4-Dichloropropionanilide-(14)C (propanil) labeled in either the C-1 or C-3
      carbon atoms of the propionic acid moiety was applied to the roots of pea (Pisum
      sativum L.) and rice (Oryza sativa L.) plants in nutrient solution (0.1 mm-0.28
      mm). Radioactivity was detected throughout the treated plants, but the greatest
      labeling was found in the roots. None of the products that contained aniline were
      radioactive, suggesting that the plants split the propionic acid moiety from
      propanil. The fate of the propionate moiety of propanil was determined by
      recovery of (14)CO(2) from plants exposed to propanil-(14)C. The time-course of
      the (14)CO(2) production demonstrated that the intact propionic acid was cleaved
      from the propanil and subsequently catabolized by the beta-oxidation catabolic
      sequence. The appearance of radioactivity in the shoots was attributed to the
      incorporation of products of propionate metabolism. Both the susceptible pea
      plants and the tolerant rice plants converted a high percentage of the
      administered propanil-(14)C to (14)CO(2).

PMID- 16656805
TI  - Studies of sulfate utilization by algae. 4. Properties of a cell-free sulfate
      reducing system from chlorella.
AB  - A cell-free system from Chlorella pyrenoidosa Chick (Emerson strain 3) which
      produces acid-volatile radioactivity from (35)SO(4) (2-) is described. A high
      speed supernatant from cells broken in the French Press at pH 7.0 shows maximal
      activity when fortified with ATP, an ATP-generating system (creatine phosphate
      and creatine phosphokinase), TPN, a TPN-reducing system (glucose-6-phosphate and
      glucose-6-phosphate dehydrogenase) and MgCl(2). This system is quite labile and
      is not stable to dialysis. Addition of low concentrations of 2,3,
      dimercaptopropan-1-ol (BAL) to the buffers used for enzyme preparation stabilize
      the extracts and permit them to be dialyzed for 4 hours without loss of activity.
      If additional BAL is also added to the incubation mixtures it can replace TPNH as
      a reductant. DPNH also shows appreciable acticity.The system prepared with BAL
      containing buffers shows maximal activity at pH 9.0. At this pH, the system
      requires only ATP, Mg(2+) and additional BAL and has high activity and stability
      compared with the other conditions tried. The optimum concentrations of these
      reactants has been determined and the kinetics of production of acid-volatile
      radioactivity are described. Nucleoside triphosphates other than ATP are not
      appreciably active in this system. In all cases, anaerobic conditions are
      required for maximal activity, the enzyme extracts are labile to heat, and no
      unequivocal requirement for thioctic acid can be demonstrated.

PMID- 16656806
TI  - Studies of sulfate utilization by algae. 5. Identification of thiosulfate as a
      major Acid-volatile product formed by a cell-free sulfate-reducing system from
      chlorella.
AB  - Separation of the products formed from sulfate-(35)S by cell-free extracts of
      Chlorella pyrenoidosa (Emerson Strain 3) has permitted the identification of
      thiosulfate as a major product which yields acid-volatile radioactivity. The
      products formed, as separated by Dowex-1-nitrate chromatography, are
      qualitatively the same whether extracts at pH 7.0 (using TPNH as the reductant)
      or extracts at pH 9 [using 2,3-dimercaptopropan-1-ol, (BAL) as reductant] are
      employed. While thiosulfate can be separated without the addition of carrier, the
      inclusion of carrier improves the recovery. High concentrations of ATP which have
      been shown previously to inhibit the formation of acid-volatile radioactivity
      from radioactive sulfate, inhibit the formation of thiosulfate almost completely.
      Degradation of the thiosulfate formed at normal ATP concentrations reveals that
      most of the radioactivity is in the SO(3)-sulfur of the molecule suggesting that
      the SH-sulfur is derived from the enzyme extracts. If carrier sulfite is present
      during thiosulfate formation from sulfate-(35)S, radioactive sulfite is recovered
      at the expense of radioactive thiosulfate. Reconstruction experiments utilizing
      specifically-labeled thiosulfates indicate that radioactive sulfite formation is
      probably not the result of trapping a normal intermediate, but can be attributed
      to non-enzymatic exchange between labeled thiosulfate formed from sulfate and the
      non-radioactive sulfite added, suggesting that free sulfite is not an
      intermediate in thiosulfate formation from sulfate.

PMID- 16656807
TI  - Studies of Sulfate Utilization by Algae. 6. Adenosine-3'-Phosphate-5'
      Phosphosulfate (PAPS) as an Intermediate in Thiosulfate Formation From Sulfate by
      Cell-Free Extracts of Chlorella.
AB  - When cell-free preparations of Chlorella pyrenoidosa Chick (Emerson strain 3)
      form thiosulfate from labeled sulfate, another radioactive compound also appears.
      This compound has been isolated in quantity and is shown to be identical with
      adenosine-3'-phosphate-5'-phosphosulfate (PAPS) on the basis of its
      chromatographic and electrophoretic behavior, chemical composition, sensitivity
      to selective degradative enzymes, and its ability to serve as a substrate for rat
      liver aryl sulphotransferase. In addition, as expected for PAPS, the compound on
      mild acid treatment yields all of its radioactive sulfur as sulfate, and is
      converted to a compound identical with adenosine-3',5'-diphosphate (PAP).
      Replacement of sulfate and ATP by this PAP(35)S in the usual incubation mixture
      yields the same product, thiosulfate, which can be isolated as such or detected
      as acid-volatile radioactivity. This conversion of PAP(35)S to thiosulfate still
      requires the addition of Mg(2+) and a reductant such as 2,3-dimercaptopropan-1-ol
      (BAL). The cause of our previous result that high concentrations of ATP inhibit
      thiosulfate formation from sulfate can be ascribed to a small amount of PAP
      contaminating the ATP preparations, since PAP proves to be an exceedingly
      effective inhibitor of the conversion of PAP(35)S to thiosulfate. Sulfate
      reduction to thiosulfate by Chlorella extracts is discussed and compared with
      similar systems from other organisms.

PMID- 16656808
TI  - Studies of Sulfate Utilization by Algae. 7. In vivo Metabolism of Thiosulfate by
      Chlorella.
AB  - Chlorella pyrenoidosa Chick (Emerson strain 3) utilizes thiosulfate for growth as
      effectively as sulfate, and more effectively than a variety of organic sulfur
      compounds containing sulfur in various oxidation states. Thiosulfates,
      differentially labeled with (35)S in either the SH- or SO(3) - sulfur moieties,
      were used to follow the incorporation of thiosulfate-sulfur into constituents of
      the insoluble fraction and of the soluble pools. Labeled sulfate was also used
      for purposes of comparison. Label from both sulfur atoms of thiosulfate and from
      sulfate is incorporated into the cysteine, homocysteine, and glutathione of the
      soluble pools, and into the methionine and cystine of protein in the insoluble
      fraction. Label from SO(3)-sulfur of thiosulfate is incorporated more slowly into
      protein methionine and cystine than label from the SH-sulfur. Moreover, the SO(3)
      sulfur of thiosulfate is recovered largely as sulfate in both the soluble pools
      and the insoluble fraction, while only a trace of SH-sulfur is recovered as
      sulfate in either case. Consistent with this, the metabolism of the SO(3)-sulfur
      of thiosulfate more closely resembles the metabolism of sulfate. Thus it would
      appear that exogenous thiosulfate undergoes early dismutation in which the SO(3)
      sulfur is preferentially oxidized, and the SH-sulfur is preferentially
      incorporated in a reduced state. These results are discussed in relation to the
      conversion of sulfate to thiosulfate by cell-free extracts of Chlorella
      previously described.

PMID- 16656809
TI  - Plant leaf and stem proteins. I. Extraction and electrophoretic separation of the
      basic, water-soluble fraction.
AB  - Simplified but highly reproducible extraction and electrophoretic procedures have
      been developed for plant stem and leaf proteins using recent chemical and
      technical advances. The method is applied to the separation of the basic, water
      soluble proteins found in stem and leaf tissues of 3 Dianthus clones. While most
      of the highly reproducible protein bands appear in all 3 selections, and many are
      also common to both leaf and stem tissue, others are characteristic for the
      variety or tissue.

PMID- 16656810
TI  - Transport of rubidium absorbed by the apex of the bean root.
AB  - Rubidium-86 was applied to the terminal 5.0 mm region of intact roots for a 6
      hour period. The plants were then harvested after 0, 18, 24, 48, 72, or 96 hours
      additional growth in a rubidium-free continuously renewed nutrient solution. A
      substantial portion of the rubidium absorbed in a region of the root devoid of
      functional xylem tissue was ultimately transported to more basipetal regions.

PMID- 16656811
TI  - Transitory Aspects of a Single Protein in Tissues of Solanum tuberosum and Its
      Coincidence With the Establishment of New Growth.
AB  - Qualitative and quantitative estimation of a proteinaceous chymotrypsin inhibitor
      in tissues of potato plants has revealed a transitory existence in all tissues
      except xylem, flowers, and seeds, where the inhibitor was not found. The
      distribution pattern in both aerial tissues and in tubers during development and
      senescence suggests that the concentrations of this protein in all tissues are
      influenced by meristematic regions of the plants. The transitory existence
      coinciding with breaking of apical dominance suggests that in the potato plant
      the protein may have some role in the process of establishing and maintaining
      meristematic tissue. A search for the protein in other Solanaceae species and in
      plants from non-related species has proven unsuccessful.

PMID- 16656812
TI  - Respiratory Electron Transport Systems of Aquatic Fungi. I. Leptomitus lacteus
      and Apodachlya punctata.
AB  - The electron transport systems of 2 species of aquatic fungi, Leptomitus lacteus
      and A podachlya punctata, contained cytochrome a-a(3) (605 mmu), 2 b type
      cytochromes (564 and 557 mmu), c type cytochrome (551 mmu), and flavoprotein, but
      they appeared to lack cytochrome c(1). Reduced-minus-oxidized difference spectra
      and difference spectra in the presence of antimycin A or cyanide were used to
      characterize these systems. Studies with the electron microscope revealed that
      hyphae of Leptomitus lacteus contained numerous, conspicuous mitochondria with
      tubular cristae.

PMID- 16656813
TI  - Studies on electron-transport reactions of photosynthesis in plastome mutants of
      oenothera.
AB  - Fluorescence characteristics and light-induced absorbance changes of 5 plastome
      mutants of Oenothera, all having a defect in photosynthesis, were investigated to
      localize the site of the block in their photosynthetic mechanism and to relate
      mutational changes in the plastome to specific biochemical events in
      photosynthesis. In 4 of the mutants examined photosystem 2 was largely, or
      completely, nonfunctional. Excitation of system 2 did not cause reduction of
      oxidized cytochrome f in these mutants. The system-2 dependent absorbance change
      at 518 mmu seen in normal leaves was absent in the mutants. Moreover, the mutants
      had a high initial fluorescence in the presence and in the absence of 3- (3,4
      dichlorophenyl)-1,1-dimethylurea, which did not change during illumination,
      indicating that the reaction centers of system 2 were affected by the mutations.
      Photosystem 1 functioned normally.A fifth mutant had an impaired photosystem 1.
      Even high intensity far-red light did not lead to an accumulation of oxidized
      cytochrome f as was seen in normal plants. Photosystem 2 was functioning, as
      evidenced by the fast reduction of the primary system-2 oxidant, and by the
      characteristics of the 518-mmu absorbance change.Because 1 of the 2 photosystems
      is functional in all mutants, and because they all have the enzymes of the
      photosynthetic carbon cycle, it appears that the effect of the mutation is
      specific. The results suggest that the plastome controls reactions within the
      electron-transport chain of photosynthesis.

PMID- 16656814
TI  - Endogenous gibberellins of a radiation induced single gene dwarf mutant of bean.
AB  - The distribution of endogenous gibberellins in Dwarf-1, a single gene dwarf
      mutant of Mexico 80-R red beans, was studied. Parallel extraction and
      fractionation of seeds of this mutant and those of a normal homozygous line
      followed by thin layer chromatography and bioassays using Rumex obtusifolius,
      wheat seed endosperm and dwarf bean plants revealed that a stem elongation
      control factor was contained in the non-acidic fraction from normal, but not from
      Dwarf-1, seeds. It was concluded that the single gene mutation causes a block
      either in gibberellin precursor formation or in production of a non-acidic
      fraction gibberellin-like substance.

PMID- 16656815
TI  - Metabolism of alpha-Ketoglutarate by Roots of Woody Plants.
AB  - The uptake and metabolism of alpha-ketoglutarate-5-(14)C by peach, apple, and
      privet root tissues were studied over various time intervals. As much as 80% of
      the absorbed (14)C appeared as (14)CO(2) in 320 minutes in peach roots. Apple and
      privet roots were less effective in this conversion with the bulk of the (14)C
      found in the organic acid fraction. This indicates differences in organic acid
      metabolism among species of woody plants.The (14)C accumulated in malate earlier
      and in larger quantities than in citrate. Both glutamate and aspartate were
      labeled in 10 minutes and glutamate was labeled as early as 3 minutes. The
      labeling pattern does not clearly distinguish between the synthesis of glutamate
      by glutamic dehydrogenase or by transamination with oxaloacetate.The rapid
      metabolism of alpha-ketoglutarate to glutamate by the 3 species studied indicates
      the presence of enzyme systems important in amino acid synthesis in the roots of
      woody plants.

PMID- 16656816
TI  - An electrophoretic analysis of the isozymes of malate dehydrogenase in several
      different plants.
AB  - The particulate and soluble fractions of cell-free extracts from seeds, roots,
      and leaves of 10 different plants were examined electrophoretically for isozymes
      of malate dehydrogenase. Distinct isozyme patterns were observed for each plant
      and even for the individual tissues of each species. There were some isozymes in
      several different plant extracts with equal electrophoretic mobilities, but there
      was no isozyme band that was common to all tissues or to all plants.

PMID- 16656817
TI  - Extractable and Diffusible Gibberellins From Light- and Dark-grown Pea Seedlings.
AB  - Gibberellins were obtained from light- and dark-grown peas by solvent extraction
      and agar diffusion. Both A(5)- and A(1)-like gibberellins were obtained by
      extraction; however, by diffusion only the A(1)-like gibberellin was found. There
      was no significant quantitative difference in the levels of diffusible or
      extractable gibberellin obtained from light- and dark-grown tall and dwarf peas.
      Several possible explanations for the discrepancy between diffusible and
      extractable gibberellin were investigated. Of these, only I was supported by
      experimental evidence, namely, that GA(5) can be converted to GA(1).

PMID- 16656818
TI  - Respiratory Response of Acer pseudoplatanus Cells to Pyruvate and 2,4
      Dinitrophenol.
AB  - The endogenous respiration rate of unstarved cultured cells of Acer pseudo
      platanus L. is markedly stimulated by 2,4-dinitrophenol. Pyruvate is also
      stimulatory but to a lesser degree than dinitrophenol. Exogenously supplied
      sugars cause no short-term stimulation. Pyruvate does not enhance the elevated
      rate of O(2) uptake in the presence of dinitrophenol but does cause additional
      CO(2) evolution. The endogenous concentration of pyruvate is elevated in the
      presence of dinitrophenol. These observations suggest that the rate of O(2)
      uptake by the unstarved intact cells is limited by the rate of glycolysis and
      that rate of glycolysis is regulated by the intracellular concentration of
      adenine nucleotides or inorganic phosphate. Dinitrophenol stimulation of
      endogenous respiration is due in part to an indirect acceleration of glycolysis
      but also to a more direct facilitation of oxidation in the presence of excess
      mitochondrial substrate.

PMID- 16656819
TI  - Inhibitory Effects of Dichlorophenoxyacetones on Auxin-induced Growth of Avena
      Coleoptile Sections.
AB  - Six dichlorophenoxyacetones were synthesized and examined as potential metabolic
      antagonists utilizing Avena coleoptile sections and the straight growth assay
      procedure. Supplements of indoleacetic acid promoted growth of the sections which
      were inhibited by the analogs; the most inhibitory derivatives were 2,3-; 2,4-;
      2,5-; and 3,4-dichlorophenoxyacetone which produced half-maximal growth responses
      (relative to the unaug-mented control growth) at concentrations of 106, 86, 80,
      and 62 mug/ml, respectively. A Lineweaver-Burk plot of the data for the
      inhibition by 2,4-dichlorophenoxyacetone and its reversal by indoleacetic acid
      appeared to represent an uncompetitive-like inhibition.

PMID- 16656820
TI  - Adenine phosphoribosyltransferase in plant tissues: some effects of kinetin on
      enzymic activity.
AB  - Adenine phosphoribosyltransferase activity was measured in extracts of soybean
      (Glycine max var. Acme) callus and of senescing barley leaves (Hordeum distichon
      c.v. Prior). The enzyme from soybean callus had Michaelis constants for adenine
      and 5-phosphoribosyl pyrophosphate of 1.5 and 7.5 mum respectively and was
      inhibited by AMP and stimulated by ATP. The presence of kinetin was found to
      considerably increase the activity of adenine phosphoribosyltransferase in
      extracts of soybean callus and senescing barley leaves.

PMID- 16656821
TI  - Evidence for the participation of the reductive pentose phosphate cycle in
      photoreduction and the oxyhydrogen reaction.
AB  - The assimilation of (14)C-sodium bicarbonate has been measured in Scenedesmus
      obliquus as 1) photosynthesis, 2) photoreduction (light dependent incorporation
      of carbon dioxide by hydrogen adapted cells under conditions where photosynthesis
      is inoperative), and 3) the oxyhydrogen reaction (dark assimilation of carbon
      dioxide by hydrogen adapted cells in an atmosphere of hydrogen and 1% oxygen).
      Degradation of the glucose formed in each of these reactions using the
      Leuconostoc technique establishes the participation of the reductive pentose
      phosphate cycle.

PMID- 16656822
TI  - De Novo Synthesis of Isocitritase in Peanut (Arachis hypogaea L.) Cotyledons.
AB  - Germination of peanut seed is accompanied by a rapid increase in isocitritase
      (isocitrate lyase, EC 4.1.3.1) during the first 4 days. The presence of
      cycloheximide (50 mug/ml) during water imbibition inhibited the increase in
      isocitritase activity. Actinomycin D conversely did not inhibit isocitritase
      activity until the second day of imbibition while RNA synthesis was inhibited.
      Germination of peanut seed in (14)C-reconstituted amino acids followed by
      fractionation of a 20 to 35% ammonium sulfate preparation on a Sephadex G-200
      column (57-fold purification) showed that the active enzymic fraction coincided
      with a large peak of radioactivity. Germination of peanut seed in 45% D(2)O
      followed by enzyme purification and CsCl equilibrium centrifugation revealed that
      all the enzyme from D(2)O seed had a higher density than normal isocitritase.
      These data indicate that isocitritase in peanut seed is synthesized de novo.

PMID- 16656823
TI  - Evidence for de novo synthesis of isocitratase and malate synthesis in
      germinating peanut cotyledons.
AB  - Evidence for de novo synthesis of isocitratase and malate synthetase in
      cotyledons of germinating peanut (Arachis hypogaea L.) was obtained by the
      density labeling method. When dry peanut cotyledons were cultured in H(2) (18)O,
      a 2.4% increase in the buoyant density of malate synthetase in a cesium chloride
      gradient was observed. In 100% D(2)O the buoyant density shift was 5.5% for
      isocitratase and 3.5% for malate synthetase in comparison to the water controls.
      These data suggest that isocitratase and malate synthetase do not pre-exist in
      some inactive form in the cotyledons, but are completely synthesized after onset
      of germination from a pool of amino acids which do not derive directly from
      hydrolysis of storage proteins.

PMID- 16656824
TI  - Gas chromatography of carbohydrates in alfalfa nectar.

PMID- 16656825
TI  - Effect of fluoride on nucleotides and ribonucleic Acid in germinating corn
      seedling roots.
AB  - Investigation was made for the effect of fluoride on plant growth, acid soluble
      nucleotides, and RNA in germinating corn seedling roots. Fluoride suppresses root
      growth as measured by changes in fresh weight. Column chromatographic analyses
      demonstrated that fluoride modifies ratios of acid soluble nucleotide species.
      The relative amount of nucleotides is altered mainly due to triphosphate
      nucleotides of which ATP is most accumulated. Paper chromatographic analyses
      showed that fluoride induces changes of RNA structure. The RNA is characterized
      by lowered relative content of cytosine and by increased ratio of cytosine to
      guanine. Adenine is depressed significantly only in the root tissue treated by
      the highest fluoride concentration.

PMID- 16656826
TI  - Polar Movement of Indole-3-acetic Acid-C in Roots of Lens and Phaseolus.
AB  - A critical review of the few papers on IAA-(14)C movement in roots revealed
      apparent contradictions, as well as flaws in experimental design that would be
      apt to cause artifacts. The movement of (14)C from IAA-(14)C was studied in
      sections of Lens and Phaseolus roots, using a system 20 or more times as
      sensitive as any previously used. To make sure that our results with roots could
      be compared validly with published work on petioles and stems, we used the same
      techniques as we had earlier used for shoot structures. The results with Lens
      were similar in many ways to those for shoots: net movement into receiver blocks
      was very strongly polar, followed a linear course for several hours, and showed a
      velocity of the same order of magnitude as in shoots (and, in fact, very close in
      absolute value to that found in Coleus stem cylinders). Also, as with shoots, all
      the radioactivity in receiver blocks ran to the R(F) of IAA. The time-course of
      loss of counts from donor blocks was similar to that found in shoots. The 2 most
      striking differences from shoots were 1) the very low percentage of added (14)C
      that was moved into the receivers (about one-tenth of the values for bean
      petioles), and 2) the fact that the polar movement was acropetal in roots, rather
      than basipetal as in shoots. Results with Phaseolus roots were similar to those
      for Lens, although an additional complication with Phaseolus roots was the
      indication of a transitory stage of weak basipetal polarity in the first few
      hours after excising the section. This stage was followed in a few hours by a
      stronger acropetal polarity.

PMID- 16656827
TI  - Metabolic Regulation in Diseased Leaves II. Changes in Nicotinamide Nucleotide
      Coenzymes in Barley Leaves Infected With Powdery Mildew.
AB  - Nicotinamide nucleotide coenzymes were estimated spectrophotometrically in
      noninfected barley leaves and leaves infected with Erysiphe graminis var hordei
      (powdery mildew). Amounts of NADH, NADP(+) and NADPH were not altered by
      infection. In contrast, the NAD(+) content rose sharply and at 144 hours was 100%
      greater than in noninfected leaves. The respiratory rate was increased in
      infected leaves and the pattern of this increase was similar to that of
      NAD(+).The effect of infection on the intracellular distribution of NADP(+) was
      examined by fractionating lyophilized leaves in a nonaqueous medium. In
      noninfected leaves almost all of the NADP(+) was localized in the chloroplasts.
      In infected leaves where some chloroplast breakdown occurs, about 60% of the
      NADP(+) was detected in the nonchloroplast part of the cell. This intracellular
      redistribution of NADP(+) is discussed in relation to the increased pentose-P
      pathway activity occuring after infection.

PMID- 16656828
TI  - Light sensitivity of plastids and plastid pigments present in the albescent maize
      mutant.
AB  - Dark grown albescent corn seedlings are deficient in colored carotenoids but
      accumulate phytoene, phytofluene and an unidentified substance in the carotenol
      fraction. They bleach upon exposure to bright light and appear albino. Seedlings
      grown under low level incandescent light are normal in appearance and contain
      almost as much colored carotenoid as control seedlings. The existing leaf tissue
      of seedlings grown under low level light does not bleach upon exposure to bright
      light. The enhanced carotenoid synthesis and stabilization of plastids is not
      affected by brief illumination with red light but requires several hours of low
      level incandescent light.

PMID- 16656829
TI  - Pulvini as the Photoreceptors in the Phytochrome Effect on Nyctinasty in Albizzia
      julibrissin.
AB  - The fact that far-red pretreatment slows the closing response of Albizzia
      julibrissin pinnules to darkness was used to locate the photoreceptor region for
      the role of phytochrome in nyctinasty, and to determine whether the effect is
      localized or translocated. Illumination of pinnule tissue alone induced no
      response, while illumination of an area as narrow as 1 mm, including only the
      tertiary pulvini and adjacent portions of rachilla and pinnules, was sufficient
      for a full response. This suggests that the pulvini themselves, the sites of the
      response, act as photoreceptors. In experiments with various shielding devices,
      pinnules on the same rachilla responded independently to local illumination,
      suggesting the absence of any translocatable effects.

PMID- 16656830
TI  - Characterization of glyoxysomes from castor bean endosperm.
AB  - Electron micrographs are presented which establish the identity of the components
      of the 3 major bands observed after sucrose density centrifugation of the crude
      particulate fraction from the endosperm of germinating castor bean seedlings.
      These are: mitochondria (density 1.19 g/cc), proplastids (density 1.23 g/cc) and
      glyoxysomes (density 1.25 g/cc). Further evidence is provided on the enzymatic
      composition of the glyoxysomes. Essentially all of the particulate malate
      synthetase, isocitrate lyase, catalase, and glycolic oxidase is present in these
      organelles. The distribution of glyoxysomal enzymes on sucrose density gradients
      is contrasted with that of the strictly mitochondrial enzymes fumarase, NADH
      oxidase, and succinoxidase. Malate dehydrogenase and citrate synthetase are
      present in both organelles. The functional role of glyoxysomes and their
      relationship to cytosomes from other tissues is discussed.

PMID- 16656831
TI  - Effects of Light on the Growth and Development of the Liverwort, Sphaerocarpos
      donnellii Aust.
AB  - Fragments of thalli of the liverwort, Sphaerocarpos donnellii Aust., inoculated
      into liquid medium containing sucrose and mineral salts, attain a much greater
      dry weight after 9 days growth in continuous white light than in darkness. Light
      causes this difference by increasing the rate of growth of the plants. This
      growth response is mediated by the pigment systems of photosynthesis and
      phytochrome. An inhibitor of photosynthesis, DCMU, at concentrations which
      inhibit light-mediated CO(2) fixation, decreases the growth rate of light-grown
      but not dark-grown plants. Light still slightly increases the growth rate of
      plants in the presence of DCMU. This latter response is mediated by phytochrome,
      since it can be effected by a 2 minute exposure to low intensity red light every
      12 hours, and far-red light reverses the effect of red. The increased growth rate
      effected by red light is related to a change in the morphology of the plants.
      Dark-grown plants form compact balls of tissue consisting of lobes. These lobes
      are rounded and thick and exhibit an abnormal callus-type growth, with few well
      defined meristematic regions. Plants grown in red light form fluffy balls of
      tissue. The lobes of these plants have a morphology more typical of Sphaerocarpos
      in nature. They are 2 cell layers thick, flattened, and have numerous well
      defined meristematic areas. The greater number of meristems allows for the
      increased growth rate of the plants grown in red light.

PMID- 16656832
TI  - Light Mediated Changes in the Chloroplasts of the Liverwort, Sphaerocarpos
      donnellii Aust.
AB  - Dark-grown plants of Sphaerocarpos, incubated in a liquid medium containing
      sucrose and mineral salts, have a much lower chlorophyll and nitrogen content
      than do light-grown plants. Two minutes of red light per 12 hours is about two
      thirds as effective in increasing chlorophyll and nitrogen content as is
      continuous white light. These red light-induced increases are mediated by
      phytochrome, as they are reversible by alternating exposures to red and far-red
      light. They appear to be related to differences in the ultrastructure of the
      chloroplasts. Plastids from dark-grown plants are full of starch and develop few
      lamellae, while light-grown plastids contain little starch and have many
      lamellae. The ultrastructural studies are supported by starch determinations
      which revealed a phytochrome-mediated decrease in starch content. The effect of
      white light in increasing the chlorophyll and nitrogen content above the level
      attained in red light-treated plants is not mediated by photosynthetic activity.
      These results are related to similar responses in other archegoniates and
      angiosperm seedlings.

PMID- 16656833
TI  - Pyruvate Kinase Activity of Wheat Plants Grown under Potassium Deficient
      Conditions.
AB  - The activity of pyruvate kinase was determined in the first leaves of wheat
      plants grown under K(+)-deficient conditions. An enhancement of the enzyme
      activity compared with the normal plants was found to start from eighth day of
      growth, and about 4-fold increase in the enzyme activity was observed in 14-day
      wheat leaves. The addition of K(2)SO(4) to the nutrient solution given to the
      K(+)-deficient plants at tenth day resulted in the restoration of the enzyme
      activity to the normal level after 3 days. The levels of K(+) as well as
      carbohydrates and chlorophyll were found to return normal over the same period.
      These findings are discussed in relation to the metabolic pattern of plants at
      the early stages of K(+)-deficiency.

PMID- 16656834
TI  - Indoleacetic Acid and the synthesis of glucanases and pectic enzymes.
AB  - Indoleacetic acid (IAA) and/or inhibitors of DNA, RNA or protein synthesis were
      added to the apex of decapitated seedlings of Pisum sativum L. var. Alaska. At
      various times up to 4 days, enzymic protein was extracted from a segment of
      epicotyl immediately below the apex and assayed for its ability to hydrolyse
      polysaccharides or their derivatives. With the exception of amylase, the total
      amounts per segment of all of the tested enzymes increased due to IAA treatment.
      The development of beta-1,4-glucanase (cellulase) activity per unit of protein or
      fresh weight proceeded according to a typical sigmoid induction curve. Pectinase
      was formed for about 2 days in control segments and IAA treatment resulted in
      continued synthesis for at least another 2 days provided cell division took
      place. beta-1,3-glucanase and pectinesterase activities were only enhanced by IAA
      to the extent that total protein levels increased. Reaction mechanisms for these
      effects and functions for the enzymes during growth are discussed.

PMID- 16656835
TI  - Induction and prevention of chilling injury to radicle tips of imbibing
      cottonseed.
AB  - Cottonseed exposed to a temperature of 5 degrees during hydration are killed, or
      the subsequent germination performance of surviving seed is seriously inhibited.
      Exposure to chilling for periods as short as 30 minutes reduces germination speed
      and induces root abnormalities, while chilling for 12 hours may kill all seed.
      Sensitivity to chilling persists during the initial 2 to 4 hours of hydration.
      Seeds imbibed 4 hours at 31 degrees , then dried, retain immunity to chilling. An
      irreversible event that is blocked or disrupted by chilling apparently occurs
      during early seed hydration.

PMID- 16656836
TI  - Interpretation of the dual isotherm for ion absorption in beet tissue.
AB  - Beet discs aged in 0.5 mM CaSO(4) develop a capacity to absorb K(+) and Cl(-)
      from solutions of low concentration. The initial influx of these ions is
      described by a hyperbolic relationship with concentration in the range 0.01 to
      0.5 mM KCl, which is identical with the system 1 absorption isotherm found in
      other tissues. A second hyperbolic isotherm, attributable to system 2, is found
      at higher concentrations (1-50 mM KCl).When the transport of labeled ion to the
      vacuole is studied by wash-exchanging the bulk of the cytoplasmic label following
      the absorption period, it is noted that in the range of system 1, isotope influx
      to the vacuole increases with time as the concentration of labeled ions in the
      cytoplasm increases, while in the range of system 2, influx to the vacuole is
      constant from the beginning. Diminution of the cytoplasmic specific activity
      during radio-isotope absorption by prefilling the cytoplasm with the analogous
      unlabeled salt, markedly reduces subsequent radioisotope uptake to the vacuole
      only in the range of system 1. These experiments suggest that the cytoplasm
      serves as a mixing chamber, and that the plasma membrane controls ion uptake to
      the tissue at low concentrations, indicating that the system 1 isotherm reflects
      ion movement into the cytoplasm through the plasma membrane. Flux experiments
      support this conclusion, showing that development with age of the system 1
      isotherm corresponds to a quantitatively similar increase in plasma membrane
      influx in 0.2 mM KCl.At higher concentrations the outer membrane no longer rate
      limits entry of ions to the vacuole. Isotope influx under these conditions,
      described by the system 2 isotherm, presumably reflects movement across the
      tonoplast.

PMID- 16656837
TI  - The respiratory chain components of higher plant mitochondria.
AB  - TIGHTLY COUPLED MITOCHONDRIA HAVE BEEN PREPARED FROM A VARIETY OF PLANT SOURCES:
      white potato (Solanum tuberosum), Jerusalem artichoke (Heliantus tuberosus),
      cauliflower buds (Brassica oleracea), and mung bean hypocotyls (Phaseolus
      aureus). Mitochondria with no appreciable coupling were also prepared from skunk
      cabbage spadices (Symplocarpus foetidus).Room temperature difference spectra show
      that these mitochondria are very similar in the qualitative and quantitative
      composition of their electron carriers. The different cytochromes are present in
      the amounts of 0.1 to 0.3 mmumole per mg of mitochondrial protein. The molar
      ratios of the different electron carriers are, on the average: 0.7:0.7:1.0:3 to
      4:10 to 15 respectively for cytochrome aa(3), cytochromes b, cytochromes c,
      flavoproteins, and pyridine nucleotides.From low temperature difference spectra
      carried out under particular experimental conditions, it can be deduced that
      these mitochondria contain 3 b cytochromes whose alpha bands are located at 552,
      557, and 561 mmu, and 2 c cytochromes, one of which, a c(1)-like cytochrome, is
      firmly bound to the mitochondrial membrane. Cytochrome oxidase can be optically
      resolved into its 2 components a and a(3).For all kinds of mitochondria, the
      rates of oxidation of succinate are similar as well as the turnover of cytochrome
      oxidase (50-70 sec(-1)), regardless of the metabolic activities of the tissues.
      The number of mitochondria per cell appears to be the controlling factor of the
      intensity of tissue respiration.

PMID- 16656838
TI  - In vitro phytochrome dark reversion process.
AB  - Thermal reversion of the far-red absorbing form of phytochrome to the red
      absorbing form in darkness has been investigated in crude and partially purified
      isolates from a number of etiolated and light grown higher plants. The influence
      of temperature, aging and urea on the rate of reversion was also
      determined.Phytochrome isolated from all higher plants underwent reversion. The
      reversion proceeded in at least 2 distinct stages; a short rapid initial phase
      being followed a slow phase which continued for many hours. Reversion rate was
      highest in phytochrome isolated from green leaves of parsnip (Pastinacea sativa)
      and lowest in that isolated from etiolated oats (Avena sativa). Although the rate
      of reversion could be changed by modifying the tertiary structure of the protein
      component, the large differences in rate appeared to be characteristic of the
      plant source. Observed in vitro rates of reversion are slower than those
      occurring in vivo. Removal of other buffer solubilized material during
      purification had little effect on the rate of reversion of phytochrome isolated
      from etiolated material.

PMID- 16656839
TI  - Evidence for a role of calcium in nitrate assimilation in wheat seedlings.
AB  - Severely Ca-deficient Triticum aestivum L. seedlings accumulated high levels of
      nitrite and moderate levels of nitrate and organic nitrogen, but contained
      unaltered levels of hydroxylamine. Nitrite accumulation was not related to
      molybdenum deficiency, or altered cellular pH. Nitrate reductase was decreased by
      Ca deficiency, apparently by repression of enzyme synthesis from accumulated
      nitrite and not by inhibition of enzyme activity. Nitrite reductase and NADP
      diaphorase activities were not affected by Ca deficiency, and Ca did not restore
      activity to nitrite reductase inactivated by cyanide. The results indicated that
      the role of Ca is in intracellular transport of nitrite and not in induction or
      activity of enzymes.

PMID- 16656840
TI  - Light-Induced Chloroplast Shrinkage in vivo Detectable After Rapid Isolation of
      Chloroplasts From Pisum sativum.
AB  - A light-induced shrinkage of chloroplasts in vivo could be detected with
      chloroplasts isolated within 2 minutes of harvesting pea plants. As determined
      both by packed volume and Coulter counter, the mean volume of chloroplasts from
      plants in the dark was 39 mu(3), whereas it was 31 mu(3) for chloroplasts from
      plants in the light. Upon illumination of the plants, the half-time for the
      chloroplast shrinkage in vivo was about 3 minutes, and the half-time for the
      reversal in the dark was about 5 minutes. A plant growth temperature of 20
      degrees was optimal for the volume change. The chloroplast shrinkage was half
      maximal for a light intensity of 400 lux incident on the plants and was light
      saturated near 2000 lux. The light-absorbing pigment responsible for the volume
      change was chlorophyll. This light-induced shrinkage resulted in a flattening and
      slight indenting of the chloroplasts. This chloroplast flattening upon
      illumination of the plants may accompany an increase in the photosynthetic
      efficiency of chloroplasts.

PMID- 16656841
TI  - Role of Aldolase in Photosynthesis. II Demonstration of Aldolase Types in
      Photosynthetic Organisms.
AB  - Spinach leaves and photoautotrophically grown Euglena and Chlorella possess
      fructose 1,6-diphosphate aldolases inhibited by p-chloromercuribenzoate but
      insensitive to K(+) or ethylenediamine tetraacetate (Type I). Dark grown Euglena
      and Chlorella have aldolases inhibited by p-chloromercuribenzoate and
      ethylenediamine tetraacetate but stimulated by K(+) (Type II). The red alga,
      Chondrus, and the golden-brown alga, Ochromonas, appear to possess both types.
      Bean, pea, and spinach seeds and the leaves and cotyledons of etiolated bean
      seedlings contain a p-chloromercuribenzoate insensitive, apparently non
      sulfhydryl variant of Type I. Sensitivity of leaf aldolase to p
      chloromercuribenzoate occurs in etiolated bean seedlings only after an extended
      period of illumination. Type II aldolase activity in cell-free extracts of 4 blue
      green algae has been demonstrated.

PMID- 16656842
TI  - Immunochemical study of changes in reserve proteins of germinating soybean seeds.
AB  - Changes in the reserve proteins of soybean seeds (Glycine max) were investigated
      by the techniques of disc electrophoresis and disc immunoelectrophoresis. Three
      different antisera were used in these studies, an anti-whole soybean extract
      serum 129, an anti-11S soybean protein monospecific serum 102, and an anti-7S
      soybean protein monospecific serum 132. At least 6 antigenically distinct
      components were found to be present in the proteins of the isolated soybean
      protein bodies. These components are metabolized at different rates during
      germination. The major soybean protein (11S component) is found to be present
      even after 16 days of germination, whereas the 7S component disappears after the
      ninth day. Histochemical observations of cotyledon sections during germination
      are also reported.

PMID- 16656843
TI  - Contents and recovery of gibberellins in monoecious and gynoecious cucumber
      plants.
AB  - Diffusates from seedlings and root exudates from 6-week-old plants of a
      monoecious line of cucumber, Cucumis sativus L., contained considerably higher
      levels of gibberellin-(GA-) like substances than did those from plants of an
      isogenic gynoecious line. Most of the GA-like activity was found in a
      chromatogram region typical of GA(1) and GA(3); some activity, particularly in
      root exudates, appeared also at an R(F) similar to that of GA(4) and GA(7).When
      seedlings were treated with (3)H-labeled GA(1), more radioactivity was found in
      the diffusates from monoecious seedlings than from gynoecious ones. The same was
      true of biological activity in root diffusates from older plants which had been
      treated with gibberellin A(4+7).In conjunction with evidence present in
      literature, these results support the idea that endogenous GAs play a part in the
      regulation of sex expression in cucumber, relatively high levels favoring the
      formation of staminate flowers.

PMID- 16656844
TI  - Uncoupling of respiration-linked contraction in corn mitochondria.
AB  - Respiration-linked contraction of corn mitochondria is not noticeably reduced by
      low, uncoupling concentrations of dinitrophenol. However, if a
      contraction/respiration ratio is calculated, the contraction proves to be
      uncoupled. Previous statements that contraction cannot be uncoupled from
      respiration are in error.The uncoupling of contraction is consistent with the
      concept that dinitrophenol attacks a primary non-phosphorylated high energy
      intermediate (I approximately X). It is proposed that this intermediate is linked
      to some contractile mechanism such that the degree of contraction reflects the
      level of intermediate.

PMID- 16656845
TI  - Fate of radioactive gibberellin a(1) in maturing and germinating seeds of peas
      and Japanese morning glory.
AB  - Radioactive gibberellin A(1) ((3)H-GA(1)) was injected into excised fruits of
      peas and Japanese morning glory. These were then grown in sterile culture to
      maturity and the label was followed in the seeds during further development and
      subsequent germination. During development of both pea and morning-glory seeds a
      large part of the radioactivity became associated with the aqueous fraction,
      while another part of the (3)H-GA(1) was converted into 2 new, acidic,
      biologically active compounds, designated X(1) and X(2). A relatively small part
      of the neutral compounds could be converted back to (3)H-GA(1), X(1), and X(2) by
      means of mild acid hydrolysis. During germination of pea and morning-glory seeds,
      part of the bound compounds was released in the form of (3)H-GA(1), X(1) and X(2)
      while, particularly during rapid seedling growth, a further conversion of (3)H
      GA(1), mainly to X(1), took place. In pea seedlings, growth during the first 2 to
      3 days after imbibition was not affected by Amo-1618, an inhibitor of gibberellin
      biosynthesis. This, in conjunction with the findings on the interconversions
      between free and bound (3)H-GA(1) suggests that, at least in peas, early seedling
      growth may at least partly be regulated by gibberellins released from a bound
      form which was formed during seed development.

PMID- 16656846
TI  - Response of tissue with different phytochrome contents to various initial
      photostationary States.
AB  - Pretreatment of etiolated pea plants with red light and with red combined with
      far-red light produced morphologically similar plants having 4-fold differences
      in spectrophotometrically detectable phytochrome. Stem segments from the
      variously pretreated plants respond in the same way to different percentage
      conversions of phytochrome to P(FR). These results suggest that the P(FR)./P(R)
      ratio, rather than the concentration of P(FR), governs pea stem segment
      elongation. However, the ratio hypothesis does not explain contradictions between
      spectrophotometric and physiological assays previously obtained with this tissue,
      nor does it explain similar contradictions obtained in other systems. The only
      hypothesis consistent with the data to date is that of the existence of bulk and
      active phytochrome fractions, with the latter present in insufficient quantities
      to be spectrophotometrically detectable.

PMID- 16656847
TI  - Studies on cytokinin-controlled bud formation in moss protonemata.
AB  - Application of cytokinins to moss protonemata of the proper physiological age
      causes bud formation on specific cells (caulonema). During the early stages of
      their development, buds revert to protonemal filaments if the cytokinin has been
      removed by washing the protonemata. This indicates that the hormone is not acting
      as a "trigger" but has to be present during a critical period of time until
      differentiation is stabilized. Autoradiographs of protonemata treated with a
      labeled cytokinin, benzyladenine-benzyl-7-(14)C, show a striking accumulation of
      the radioactivity in caulonema cells which are in the stage of bud formation, and
      in the buds themselves. Cells which did not react to the hormone contained very
      little radioactivity. The accumulation of benzyladenine in the "target cells" may
      be due to the presence of binding sites which, in turn, may distinguish
      responding cells from non-responding ones.

PMID- 16656848
TI  - Vacuolar and Cytoplasmic Potassium Concentrations in Pea Roots in Relation to
      Cell-to-Medium Electrical Potentials.

PMID- 16656849
TI  - Effect of cultivation temperature on peroxidase isozymes of plant cells grown in
      suspension.

PMID- 16656850
TI  - Wheat seedling growth in the absence of gravitational force.

PMID- 16656851
TI  - Inhibition of in vitro DNA Synthesis by Auxins.

PMID- 16656852
TI  - Seasonal Changes in the Distribution of Photo-assimilated C in Young Pine Plants.
AB  - Pinus strobus L. plants in their third year of growth were permitted to
      photoassimilate (14)CO(2) for about 1 hour at monthly intervals between April and
      October, and the subsequent distribution of (14)C in these plants was determined
      8 hours, 1 month, 2 months or 4 months after photo-assimilation. In this way, the
      fate of (14)CO(2) photo-assimilated during different months of the growing season
      was observed.In the spring, old needles played a significant role in photo
      assimilating (14)CO(2) and exporting current photosynthate to the developing new
      shoots and roots. By July, the new shoot had replaced the old shoot both as the
      primary photo-assimilating part of the plant and as an exporter, particularly to
      the root.The root received current photosynthate from the shoot throughout the
      entire growing season, although plant analysis only 8 hours after photo
      assimilation did not always reveal this. Translocation of recent photosynthate
      from shoot to root was particularly high in August, September, and October.The
      amounts of photo-assimilated (14)C lost from the plants over a 4 month interval,
      principally through respiration and photorespiration, were about one-half of that
      absorbed during photo-assimilation, with the greatest loss occurring within the
      first month.

PMID- 16656853
TI  - Inhibitors from Carob (Ceratonia siliqua L.) I. Nature of the Interaction With
      Gibberellic Acid on Shoot Growth.
AB  - Concentrated whole extracts of the immature fruit of carob and 3 fractions
      derived from this extract have been shown to inhibit the gibberellic acid induced
      growth of pea seedlings. The inhibition can be completely reversed by increasing
      the amount of gibberellic acid. The inhibitors do not reduce the endogenous
      growth of seedlings but only that induced by gibberellic acid. One of the
      fractions is a newly separated one not previously reported.

PMID- 16656854
TI  - Distribution and metabolism of protein-bound hydroxyproline in an elongating
      tissue, the Avena coleoptile.
AB  - A study has been made of the distribution and metabolism of protein-bound
      hydroxyproline in an elongating tissue, the excised Avena coleoptile. The
      hydroxyproline-containing proteins of this tissue have been separated into 3
      fractions on the basis of their solubilities. The cytoplasmic, trichloroacetic
      acid-insoluble proteins (S-fraction) contain the bulk of the proline of the cells
      but only 20% of the hydroxyproline. The cytoplasm also contains a previously
      unrecognized trichloroacetic acid-soluble, non-dialyzable fraction (DS-fraction)
      which is low in proline but contains 20% of the hydroxyproline. The remaining 60%
      of the hydroxyproline is in the wall-bound, cold alkali-soluble fraction
      (extensin).Incorporation of free proline into the proline and hydroxyproline of
      all fractions is linear with time for at least 12 hours. The specific activity of
      the proline at any time is the same in all 3 fractions while the specific
      activity of the hydroxyproline is 4-times greater in the S-fraction than in the W
      fraction. During a pulse-chase experiment the specific activity of the proline
      decreases 25 to 40% in all fractions during the chase. The labeling of
      hydroxyproline in the wall increases during the chase while that of the DS
      fraction remains constant. In the S-fraction, the labeling in hydroxyproline
      rapidly drops 30 to 35% during the chase but then remains constant. It is
      concluded that the majority of the hydroxyproline-proteins in the cytoplasm are
      not transported to the wall. It is suggested that a sizeable portion of the
      cytoplasmic hydroxyproline may be located in enzymatic proteins.

PMID- 16656855
TI  - Physical forces in dormancy and germination of xanthium seeds.
AB  - The germination of seeds of Xanthium pensylvanicum Wallr. occurs in 2 phases, an
      initial passive phase of water uptake followed by an active phase of growth.
      These 2 phases have been separated experimentally, and shown to occur similarly
      in isolated cotyledons and embryonic axes. Measurements of the physical thrust
      generated by the entire seed and its separate components of cotyledon and axis
      reveal that non-dormant Xanthium seeds develop more than twice the thrust of
      dormant seeds, and that this difference develops principally in the second phase
      of enlargement of the axis. Measurement of the forces required for piercing the
      testa of these seeds establishes that whereas the thrust developed by non-dormant
      seed is adequate to cause testa rupture, that developed by dormant seeds is not.
      It is concluded that the dormancy of Xanthium involves an inadequacy in the
      embryo for rupture of the testa.

PMID- 16656856
TI  - Bidirectional translocation of sugars in sieve tubes of squash plants.
AB  - Two streams of sugars moving in opposite directions in the petiole of a half
      grown leaf were demonstrated by feeding tritiated glucose to a fully grown leaf
      of a squash plant (Cucurbita melopepo Bailey) and (14)CO(2) to the half-grown
      one. Autoradiographic evidence indicates that the movement of both streams
      occurred within the same sieve tubes. The data do not fit the mass flow theory of
      translocation which requires unidirectional flow of sugar solution in the lumen
      of the sieve tube.

PMID- 16656857
TI  - Isolation of active mitochondria from tomato fruit.
AB  - An improved method for isolating mitochondria from tomato fruit (Lycopersicon
      esculentum Mill.) is described. The fruit is chilled, and the tissue of the fruit
      wall cut by hand into very thin slices with a razor blade while immersed in a
      buffer containing 0.4 m sucrose, 2 mm MgCl(2), 8 mm EDTA, 4 mm cysteine, 10 mm
      KCl, 0.5 mg per ml bovine serum albumin 50 mm tris-HCl, pH 7.6. The pH is
      monitored and kept within the range of 7.0 to 7.2 by dropwise addition of 1 n KOH
      during cutting. The tissue is strained through 8 layers of cheesecloth and
      centrifuged at 2000 x g for 15 minutes. The supernatant is then centrifuged at
      11,000 x g for 20 minutes, and the sediment is washed once with a medium
      containing 0.4 m sucrose, 10 mm KCl, 1 mm MgCl(2), 10 mm tris-HCl, 10 mm
      KH(2)PO(4) and bovine serum albumin (0.5 mg per ml), pH 7.2. Electron microscope
      studies show that this method gives homogeneous, relatively intact mitochondria;
      they have a higher respiratory control ratio than those reported by other
      workers. The method was also tested successfully on fruits of cantaloupe and
      ;Honey Dew' melon.

PMID- 16656858
TI  - Electropotential in excised pea epicotyls.
AB  - In contrast to intact etiolated pea seedling tissue (Pisum sativum L.), excised
      segments immersed in a complete nutrient solution show marked increases in ion
      content, largely of K(+) and NO(3) (-), over a 72-hour period. During this time
      there is increase in cell electropotential difference, PD. During the initial 6
      to 8 hours there is a lag in ion uptake; cell PD, however, increases rapidly from
      approximately -50 to -100 mv then increases more slowly. The increase in PD
      precedes and thus may be a prerequisite for the rapid ion accumulation phase.
      Cell PD increases in either water or nutrient solution but eventually reaches
      higher levels in the latter. Following water pretreatment of sufficient duration
      K(+) accumulation shows no lag period. The lag phase noted here appears
      dissimilar to that of storage tissues.

PMID- 16656859
TI  - Electrostatic association and donnan phenomena as mechanisms of ion accumulation.
AB  - Excised roots of barley (Hordeum vulgare, var. Campana) were incubated for
      periods up to 24 hours in salt solutions of various concentrations and ion
      accumulation was determined at various time intervals. The data were consistent
      with the existence of 2 components of ion uptake, one accounting for ion uptake
      from solutions below 1 mm and both components contributing to uptake from
      solutions of concentrations higher than 1 mm.It is proposed that organic and
      amino acids play an important role in ion accumulation by providing nondiffusible
      charges which may bind or retain inorganic ions within the cell. Ions would enter
      the cell by diffusion or exchange from salt solutions of low concentration and
      become associated with nondiffusible organic ions, principally organic and amino
      acids. The electrostatic association between inorganic and organic ions would
      maintain a gradient and diffusion-exchange would occur until equilibrium between
      the cell and the external solution was reached. It is proposed that the
      additional component of ion uptake which becomes important at salt concentrations
      higher than 1 mm is a result of diffusion of neutral salts according to Donnan
      phenomena. Ion uptake by this proposed mechanism would not necessarily involve
      the action of carriers.

PMID- 16656860
TI  - Effect of Temperature, CO(2) Concentration, and Light Intensity on Oxygen
      Inhibition of Photosynthesis in Wheat Leaves.
AB  - The effect of 21% O(2) and 3% O(2) on the CO(2) exchange of detached wheat leaves
      was measured in a closed system with an infrared carbon dioxide analyzer.
      Temperature was varied between 2 degrees and 43 degrees , CO(2) concentration
      between 0.000% and 0.050% and light intensity between 40 ft-c and 1000 ft-c. In
      most conditions, the apparent rate of photosynthesis was inhibited in 21% O(2)
      compared to 3% O(2). The degree of inhibition increased with increasing
      temperature and decreasing CO(2) concentration. Light intensity did not alter the
      effect of O(2) except at light intensities or CO(2) concentrations near the
      compensation point. At high CO(2) concentrations and low temperature, O(2)
      inhibition of apparent photosynthesis was absent. At 3% O(2), wheat resembled
      tropical grasses in possessing a high rate of photosynthesis, a temperature
      optimum for photosynthesis above 30 degrees , and a CO(2) compensation point of
      less than 0.0005% CO(2). The effect of O(2) on apparent photosynthesis could be
      ascribed to a combination of stimulation of CO(2) production during
      photosynthesis, and inhibition of photosynthesis itself.

PMID- 16656861
TI  - A detailed evaluation of the possible contribution of bacteria to radioactive
      precursor incorporation into nucleic acids of plant tissues.
AB  - An investigation of the possible contribution of bacteria to the labeling
      patterns of soybean seedling nucleic acid was made. The results using sucrose
      gradient, MAK column, and acrylamide gel electrophoretic fractionation together
      with base composition analyses of nucleic acid preparations show that
      contaminating bacteria do not contribute to the incorporation of (32)P
      orthophosphate into the RNA of excised hypocotyl or soybean root tip. Sterile,
      non-sterile, and CM-treated soybean hypocotyl synthesize D-RNA to the same
      extent. The contaminating bacteria do not synthesize an AMP-rich RNA. The G-C
      rich (32)P-DNA component of the soybean tissues used in these studied results, at
      least primarily, from the incorporation by contaminating bacteria. CM can be used
      successfully to eliminate the contribution of bacteria to the labeling of nucleic
      acids by etiolated plant tissues. Bacterial counts, although valuable, are not
      sufficient to determine if contaminating bacteria will significantly contribute
      to nucleic acid labeling in plants.

PMID- 16656862
TI  - Changes in cell wall polysaccharides associated with growth.
AB  - Changes in the polysaccharide composition of Phaseolus vulgaris, P. aureus, and
      Zea mays cell walls were studied during the first 28 days of seedling development
      using a gas chromatographic method for the analysis of neutral sugars. Acid
      hydrolysis of cell wall material from young tissues liberates rhamnose, fucose,
      arabinose, xylose, mannose, galactose, and glucose which collectively can account
      for as much as 70% of the dry weight of the wall. Mature walls in fully expanded
      tissues of these same plants contain less of these constituents (10%-20% of dry
      wt). Gross differences are observed between developmental patterns of the cell
      wall in the various parts of a seedling, such as root, stem, and leaf. The
      general patterns of wall polysaccharide composition change, however, are similar
      for analogous organs among the varieties of a species. Small but significant
      differences in the rates of change in sugar composition were detected between
      varieties of the same species which exhibited different growth patterns. The cell
      walls of species which are further removed phylogenetically exhibit even more
      dissimilar developmental patterns. The results demonstrate the dynamic nature of
      the cell wall during growth as well as the quantitative and qualitative exactness
      with which the biosynthesis of plant cell walls is regulated.

PMID- 16656863
TI  - Photorespiration and Glycolate Metabolism: A Re-examination and Correlation of
      Some Previous Studies.
AB  - Some previous studies of photorespiration and glycolate oxidation were re
      examined and correlated by infra-red CO(2) analysis. Data about rate of
      photosynthesis and oxygen sensitivity indicated that complete inhibition of
      photosynthesis with 3-(3,4-dichlorophenyl)-1,1 dimethyl urea (DCMU) allowed dark
      respiration to continue in the light. Photorespiration was also inhibited. The
      oxygen sensitivity of glycolate-stimulated CO(2) production was found to be
      compatible with the proposal that glycolate is a substrate of photorespiration.
      Both ;in vivo' and ;in vitro' studies of the alga Nitella flexilis have revealed
      a pathway of glycolate oxidation similar to that of higher plants. DCMU
      inhibition of photosynthesis by Nitella gave results similar to those for the
      monocotyledons tested. Under very low light intensity, carbon dioxide
      compensation in corn was measurable but was not sensitive to high oxygen
      concentration. It appears that the lack of photorespiration in this plant is not
      the end result of efficient internal recycling of CO(2) to photosynthesis.

PMID- 16656864
TI  - Some characteristics of nitrate reductase from higher plants.
AB  - With respect to cofactor requirements, NADH, and FMNH(2) were equally effective
      as electron donors for nitrate reductase obtained from leaves of maize, marrow,
      and spinach, when the cofactors were supplied in optimal concentrations. The
      concentration of FMNH(2) required to obtain half-maximal activity was from 40- to
      100-fold higher than for NADH. For maximal activity with the corn enzyme, 0.8
      millimolar FMNH(2) was required. In contrast, NADPH was functional only when
      supplied with NADP:reductase and exogenous FMN (enzymatic generation of
      FMNH(2)).All attempts to separate the NADH(2)- and FMNH(2)-dependent nitrate
      reductase activities were unsuccessful and regardless of cofactor used equal
      activities were obtained, if cofactor concentration was optimal. Unity of NADH to
      FMNH(2) activities were obtained during: A) purification procedures (4 step, 30
      fold); B) induction of nitrate reductase in corn seedlings with nitrate; and C)
      inactivation of nitrate reductase in intact or excised corn seedlings. The NADH-
      and FMNH(2)-dependent activities were not additive.A half-life for nitrate
      reductase of approximately 4 hours was estimated from the inactivation studies
      with excised corn seedlings. Similar half-life values were obtained when
      seedlings were incubated at 35 degrees in a medium containing nitrate and
      cycloheximide (to inhibit protein synthesis), or when both nitrate and
      cycloheximide were omitted.In those instances where NADH activity but not FMNH(2)
      activity was lost due to treatment (temperature, removal of sulfhydryl agents,
      addition of p-chloromercuribenzoate), the loss could be explained by inactivation
      of the sulfhydryl group (s) required for NADH activity. This was verified by
      reactivation with exogenous cysteine.Based on these current findings, and
      previous work, it is concluded that nitrate reductase is a single moiety with the
      ability to utilize either NADH or FMNH(2) as cofactor. However the high
      concentration of FMNH(2) required for optimal activity suggests that in vivo NADH
      is the electron donor and that nitrate reductase in higher plants should be
      designated NADH:nitrate reductase (E.C. 1.6.6.1).

PMID- 16656865
TI  - Amino Acid incorporation in developing fucus embryos.
AB  - The incorporation of (14)C-leucine and (14)C-amino acid mixture into protein in
      unfertilized eggs and developing embryos of the brown alga Fucus vesiculosus L.
      was studied. Bacterial contamination was initially a problem, but it was found
      that the addition of 40 mug/ml chloramphenicol to the incubation medium would
      inhibit bacterial protein synthesis without affecting early development of the
      Fucus embryos. The kinetics of uptake and incorporation of (14)C-leucine into the
      trichloroacetic acid-soluble and -insoluble fractions indicated that the
      exogenous precursor did not equilibrate with the main soluble leucine pool before
      incorporation into protein. Uptake and incorporation of leucine by embryos 90 to
      175 minutes old were proportional to exogenous leucine concentration over the
      range 5 x 10(-6)m to 5 x 10(-3)m. Unfertilized eggs will incorporate (14)C
      leucine into protein. The rate of this incorporation increases dramatically in
      newly fertilized eggs with a maximum rate at 3.5 hours, a period of cell wall
      formation and increasing metabolic rates. Thereafter, the rate of incorporation
      declines until approximately 15 to 17 hours when it increases again concurrently
      with the onset of rhizoid initiation and cell division.

PMID- 16656866
TI  - Short-term Changes in Hexose Phosphates and ATP in Intact Cells of Acer
      pseudoplatanus L. Subjected to Anoxia.
AB  - Endogenous concentrations of hexosemonophosphates and ATP decline sharply and
      rapidly in intact cells of Acer pseudoplatanus subjected to anoxia, whereas
      fructose-1,6-diphosphate and pyruvate accumulate markedly. In view of gas
      exchange data indicating an apparent acceleration of glycolysis under anoxic
      conditions, the observed changes in glycolytic metabolite concentrations indicate
      regulation of glycolysis by phosphofructokinase.

PMID- 16656867
TI  - Photomorphogenesis in Sinningia speciosa, cv. Queen Victoria I. Characterization
      of Phytochrome Control.
AB  - The morphological development of Sinningia speciosa plants that were exposed to
      supplementary far red light was very different from that of plants receiving dark
      nights. After several nights of such irradiation, stems and petioles were
      elongated, petioles were angulated, leaf blade expansion was inhibited, plants
      were chlorotic and the accumulation of shoot dry weight was retarded.Red
      reversibility of the morphological changes potentiated by far red light indicated
      control by the phytochrome system. A high P(FR) level during the last half of the
      night inhibited stem elongation and promoted leaf blade expansion, but both of
      these processes were hardly affected by the P(FR) level during the first half of
      the night. Thus sensitivity to P(FR) was cyclic.The interpretation of our
      experiments was complicated by quantitative morphological differences resulting
      from long, as compared to short, far red irradiations.

PMID- 16656868
TI  - Photomorphogenesis in Sinningia speciosa, cv. Queen Victoria II. Stem Elongation:
      Interaction of a Phytochrome Controlled Process and a Red-requiring, Energy
      Dependent Reaction.
AB  - When Sinningia plants were grown with fluorescent light of photosynthetic
      intensity for 8 hours each day, stems became abnormally elongated when the P(FR)
      level was lowered by far red light given during the last half of several
      consecutive nights. However, plants were even taller if the source also emitted
      red light. Elongation was independent of the red/far red energy ratio if it was
      lower than one, but dependent upon irradiance at all values tested.Elongation of
      plants irradiated by a well filtered far red source was presumed to be limited by
      a shortage of respiratory substrate. Enhancement by radiation shorter than 700
      mmu was attributed to promotion of processes leading to increased substrate
      supply. Protochlorophyllide was regarded as the primary photoreceptor. Its
      photoreduction promoted chlorophyll synthesis which, in turn, increased
      photosynthetic capacity and thus substrate supply.

PMID- 16656869
TI  - Internal water balance of barley under soil moisture stress.
AB  - Leaf water potential, leaf relative water content, and relative transpiration of
      barley were determined daily under greenhouse conditions at 3 growth stages:
      tillering to boot, boot to heading, and heading to maturity. The leaf moisture
      characteristic curve (relative water content versus leaf water potential) was the
      same for leaves of the same age growing in the same environment for the first 2
      stages of growth, but shifted at the heading to maturity stage to higher leaf
      relative water content for a given leaf water potential. Growth chamber
      experiments showed that the leaf moisture characteristic curve was not the same
      for plants growing in different environments.Relative transpiration data
      indicated that barley stomates closed at a water potential of about -22 bars at
      the 3 stages studied.The water potential was measured for all the leaves on
      barley to determine the variation of water potential with leaf position. Leaf
      water potential increased basipetally with plant leaf position. In soil with a
      moisture content near field capacity a difference of about 16.5 bars was observed
      between the top and bottom leaves on the same plant, while in soil with a
      moisture content near the permanent wilting point the difference was only 5.6
      bars between the same leaf positions.

PMID- 16656870
TI  - Effects of changing stomatal width in a red pine forest on soil water content,
      leaf water potential, bole diameter, and growth.
AB  - Spraying a 16 meter tall stand of red pine (Pinus resinosa Ait.) with 10(-3)m
      phenylmercuric acetate in early June and again in mid-July resulted in the water
      use between June 1 and October 25 being reduced by almost 10%. It was
      demonstrated that this was caused by an increase in the leaf resistance with
      partial stomatal closure, which reduced absolute water potential in the needles
      by 1 to 3 bars in the middle of the day. Smaller demands were made upon the
      reserves of water in the bole of the tree as shown by the smaller bole
      contraction in the treated trees. Although needle length and dry weight were
      unaffected by the spray, radial growth was reduced by approximately 32%. The
      dependence of leaf resistance on light intensity is shown, and its independence
      from leaf water potential discussed.

PMID- 16656871
TI  - Inositol Metabolism in Plants. V. Conversion of Myo-inositol to Uronic Acid and
      Pentose Units of Acidic Polysaccharides in Root-tips of Zea mays.
AB  - The metabolism of myo-inositol-2-(14)C, d-glucuronate-1-(14)C, d-glucuronate-6
      (14)C, and l-methionine-methyl-(14)C to cell wall polysaccharides was
      investigated in excised root-tips of 3 day old Zea mays seedlings. From myo
      inositol, about one-half of incorporated label was recovered in ethanol insoluble
      residues. Of this label, about 90% was solubilized by treatment, first with a
      preparation of pectinase-EDTA, then with dilute hydrochloric acid. The only
      labeled constituents in these hydrolyzates were d-galacturonic acid, d-glucuronic
      acid, 4-O-methyl-d-glucuronic acid, d-xylose, and l-arabinose, or larger
      oligosaccharide fragments containing these units. Medium external to excised root
      tips grown under sterile conditions in myo-inositol-2-(14)C contained labeled
      polysaccharide.When label was supplied in the form of d-glucuronate, the pattern
      of labeled uronic acid and pentose units in cell wall polysaccharides resembled
      that obtained from labeled myo-inositol, indicating that both substances were
      metabolized along a common path during polysaccharide formation, and that
      methylation occurred at a step subsequent to uronic acid formation. When label
      was supplied in the form of l-methionine-methyl-(14)C, 4-O-methyl-d-glucuronic
      acid was the only labeled monosaccharide component that survived enzymatic or
      acid hydrolysis.Zea mays endosperm, a known source of phytin, developed maximal
      phytase activity after the third day of germination. Results obtained here
      suggest that myo-inositol released by hydrolysis of phytin represents the initial
      precursor of a normal, possibly predominant pathway for the formation of uronic
      acids in plants.

PMID- 16656872
TI  - Purification of protochlorophyllide holochrome.
AB  - Phototransformable protochlorophyllide holochrome was prepared from etiolated
      bean leaves. The detergent Triton X-100 in the presence of glycerol and tricine
      KOH buffer (pH 8) enhanced the extractability, specific activity, and
      phototransformability of the holochrome. Purification was achieved by
      polyethylene glycol-6000 precipitation and hydroxyl-apatite, DEAE-cellulose, and
      agarose chromatography. The presence of Triton X-100 permitted removal of the
      carotenoid contamination from the holochrome. The 678-nm absorption maximum of
      newly formed chlorophyllide a holochrome shifts to 672 nm in a temperature
      dependent manner. The purified holochrome contains 0.24 g of protein per mumole
      of protochlorophyllide. Estimation of the molecular weight of the holochrome by
      gel filtration on agarose revealed the presence of aggregates of approximately
      550,000 and 300,000. There are at least 2 chromophores per 550,000 molecular
      weight.

PMID- 16656873
TI  - The Non-essentiality of Boron for Scenedesmus.

PMID- 16656874
TI  - Active mitochondria do not produce ethylene.

PMID- 16656875
TI  - Ribosomal RNA synthesis in newly sliced discs of potato tuber.
AB  - A burst of ribosomal RNA synthesis is induced in potato tissue by slicing, and
      continues at a decreasing rate for about 12 hours. Ribosomal RNA synthesis in
      potato discs is sensitive to puromycin, in contrast to non-ribosomal RNA
      synthesis. Thus, the influence of puromycin on total RNA synthesis is significant
      only during the first 12 hours following slicing. The function of RNA made after
      12 hours in a puromycin-insensitive manner is unknown. However, it is apparently
      unrelated to protein synthesis, since it has been shown that total inhibition of
      RNA synthesis by addition of actinomycin D to potato tissue after 12 hours of
      aging has no effect upon protein synthesis during the ensuing 12 hours.

PMID- 16656876
TI  - Mutual diffusional interference between adjacent stomata of a leaf.
AB  - The mutual diffusional interference between adjacent stomata in laminar flow over
      a leaf is shown to play a decisive role in determining overall transpiration. The
      magnitude of this interference varies with the interaction of the vapor
      diffusional shells forming above each stoma and the air flow over the leaf. The
      interference decreases with increasing incident radiation and wind velocity. The
      effect of interference on the stomatal resistance to diffusion plays a major role
      in the overall variations in transpiration.

PMID- 16656877
TI  - Transport of 3-o-Methylglucose Into and Out of Storage Cells of Daucus carota.
AB  - The movement of labeled 3-o-methylglucose (MeG) into and out of thin carrot discs
      has been followed in order to gain information on sugar entry and exit
      mechanisms. Little or no metabolism of this derivative appears to occur in the
      tissue, since no products were detected either by chromatography or by analysis
      of respiratory CO(2).The curve relating entry to external concentration deviated
      somewhat from a rectangular hyperbola but suggested a carrier mechanism. Glucose
      and MeG each competitively inhibited the uptake of the other. K(i) for MeG was
      estimated to be 3 times the K(m) for its uptake.When discs incubated in MeG were
      transferred to H(2)O, MeG lost to the solution from the Free Space was re
      absorbed against a 7-fold concentration gradient.The addition of unlabeled MeG or
      glucose to the medium surrounding discs which had been maintaining a ratio of
      internal to external MeG of 75:1 brought about release of stored isotope. This
      was probably not due to exchange diffusion stricto sensu.Efflux of previously
      absorbed isotopic MeG into a medium containing unlabeled MeG or glucose was
      temperature-sensitive. The kinetics of efflux were complex and did not suggest a
      simple diffusion process related to overall MeG content. However there is
      evidence (including the falling rate of exit with time) that slow diffusion (or
      slow release from adsorption) contributed substantially to efflux. The source of
      this flow appeared to be neither the readily accessible Free Space nor the main
      storage compartment. Calculation indicated that the volume of this "slow
      diffusion compartment" might be about 1% of the total volume of the discs.

PMID- 16656878
TI  - Lateral movement of auxin in phototropism.
AB  - Lateral movement of indoleacetic acid-1-(14)C in corn coleoptiles was measured as
      radioactivity moving laterally following unilateral application of the auxin. The
      data suggest that there is an endogenous lateral movement of auxin, and that
      phototropic stimulation of the coleoptile depresses lateral movement towards the
      light and enhances lateral movement away from the light. The lateral movement was
      found to be principally as indoleacetic acid. In experiments using sunflower
      hypocotyl sections, evidence is also presented to support the suggestion that
      lateral redistribution of auxin may be effected by a deflection of auxin around a
      barrier to basipetal transport.

PMID- 16656879
TI  - Peroxidases from the extreme dwarf tomato plant. Identification, isolation, and
      partial purification.
AB  - Utilizing starch-gel electrophoresis, 12 discrete peroxidases were identified in
      purified extracts of the dwarf tomato shoot (Lycopersicon esculentum). Nine of
      the peroxidases moved toward the anode while 3 moved toward the cathode. In
      addition, a continuous peroxidase smear was separated from the above 12
      peroxidases. This smear moved toward the anode and accounted for 50% of the total
      peroxidase activity in the crude extract.Four of the major peroxidases were
      isolated and partially purified, using acetone and ammonium sulfate
      precipitations, preparative starch-gel electrophoresis and chromatography on DEAE
      and CM-cellulose.

PMID- 16656880
TI  - Measurement of turgor pressure and its gradient in the Phloem of oak.
AB  - A direct method is described for measuring the pressure in secondary phloem sieve
      tubes of oak trees. One end of a 26-gauge stainless steel tube was shaped such
      that when it penetrated the outer bark and transected a few sieve elements, it
      was stopped by the xylem so that small openings in the end allowed phloem sap to
      enter the tube. The other end of the stainless tube (phloem needle) was joined to
      a long glass capillary sealed at its other end to form a manometer for measuring
      phloem sap pressure. A method for measuring the average osmotic and turgor
      pressures in cells of leaves is also described. Phloem turgor pressures varied
      greatly in a series of phloem punctures around the trunk at 1.5 and at 6.3
      meters. The variation in turgor pressure was always greater than the variation in
      osmotic pressure. In a series of turgor pressures arranged in descending order,
      the values in a sequence for the upper level was usually a little (0-3 atm)
      larger than the values for the lower level. These results may suggest that
      translocation of assimilate is favored by a small turgor pressure gradient, but
      they do more to emphasize the complications in measuring gradients in an elastic
      low resistance distribution system composed of contiguous longitudinal conduits.
      The results also imply that the sieve tubes are inflated with assimilate fluid
      under high pressure which can readily move longitudinally and with less pressure
      drop than would be necessary if the sieve tubes were rigid.

PMID- 16656881
TI  - Fluorescence Properties of Wild-Type Chlamydomonas reinhardi and Three Mutant
      Strains Having Impaired Photosynthesis.
AB  - The wild-type strain of Chlamydomonas reinhardi and 3 mutant strains ac-21, ac
      141, and ac-115 have been compared for their fluorescence (and luminescence)
      properties. The different fluorescence levels, the rapid and slow photochemical
      responses affecting fluorescence, and the intensity of luminescence have been
      studied under various conditions: air, nitrogen, 3(p-chlorophenyl)-1,1
      dimethylurea. The strain ac-21 exhibits fluorescence properties only
      quantitatively different from those of the wild-type strain, and it is believed
      to be affected in some component of the electron transport chain between the 2
      light reactions. Both ac-141 and ac-115 have an abnormally high initial
      fluorescence level; ac-115 does not show the normal photochemical response
      associated with System II and has a very low luminescence. Mutant strains ac-141
      and ac-115 both seem to be modified in the System II photochemical center. These
      conclusions are compared with a previous analysis based on absorbance changes of
      cytochrome 559.

PMID- 16656882
TI  - Relationship of water potential to growth of leaves.
AB  - A thermocouple psychrometer that measures water potentials of intact leaves was
      used to study the water potentials at which leaves grow. Water potentials and
      water uptake during recovery from water deficits were measured simultaneously
      with leaves of sunflower (Helianthus annuus L.), tomato (Lycopersicon esculentum
      Mill.), papaya (Carica papaya L.), and Abutilon striatum Dickson. Recovery
      occurred in 2 phases. The first was associated with elimination of water
      deficits; the second with cell enlargement. The second phase was characterized by
      a steady rate of water uptake and a relatively constant leaf water potential.
      Enlargement was 70% irreversible and could be inhibited by puromycin and
      actinomycin D. During this time, leaves growing with their petioles in contact
      with pure water remained at a water potential of -1.5 to -2.5 bars regardless of
      the length of the experiment. It was not possible to obtain growing leaf tissue
      with a water potential of zero. It was concluded that leaves are not in
      equilibrium with the potential of the water which is absorbed during growth. The
      nonequilibrium is brought about by a resistance to water flow which requires a
      potential difference of 1.5 to 2.5 bars in order to supply water at the rate
      necessary for maximum growth.Leaf growth occurred in sunflower only when leaf
      water potentials were above -3.5 bars. Sunflower leaves therefore require a
      minimum turgor for enlargement, in this instance equivalent to a turgor of about
      6.5 bars. The high water potentials required for growth favored rapid leaf growth
      at night and reduced growth during the day.

PMID- 16656883
TI  - Some Properties of Potato Tuber UDPGd-fructose-2-glucosyltransferase (E.C.
      2.4.1.14) and UDPGd-fructose-6-phosphate-2-glucosyltransferase (E.C. 2.4.1.13).
AB  - Sucrose and sucrose 6-phosphate synthetase were isolated from potato tubers,
      partially purified and their properties studied. The sucrose synthetase showed
      optimum activity at 45 degrees and was inhibited competitively by ADP and some
      phenolic glucosides. The Ki's for these inhibitors were determined. Mg(2+) was
      found to activate this enzyme. Activity toward UDP-glucose or ADP-glucose
      formation was measured. The optimum conditions for sucrose and UDP-glucose
      formation were found to differ. The specificity for the glucosyl donor and
      acceptor were determined.The optimum conditions for sucrose 6-phosphate
      synthetase activity were studied. This enzyme was not inhibited by either ADP or
      phenolic glucosides; UDP-glucose was the only glucosyl donor for sucrose 6
      phosphate formation.

PMID- 16656884
TI  - Ethylene formation in pea seedlings; its relation to the inhibition of bud growth
      caused by indole-3-acetic Acid.
AB  - Indole-3-acetic acid stimulates ethylene production in the nodal region of pea
      stems, and the gas inhibits bud growth. At all concentrations of IAA there is a
      close correlation between the intensity and duration of ethylene production and
      the bud inhibition which results. Kinetin reverses the inhibitory actions of
      ethylene and IAA on bud growth. It is concluded that auxins suppress bud
      development by stimulating ethylene formation. The possibility that auxin induced
      ethylene formation controls apical dominance is considered.

PMID- 16656885
TI  - Invertase activity and cell growth in lentil epicotyls.
AB  - The activity of invertase and its relation to growth were studied in the
      epicotyls of lentil seedlings incubated in the presence and absence of
      gibberellic acid (GA(3)).Invertase activity per epicotyl increases relatively
      more rapidly than does length, reaches a maximum during most active elongation,
      and declines upon cessation of growth.GA(3) enhances both growth and increase in
      invertase activity, without altering the kinetics of the 2 processes. If GA(3) is
      added during incubation invertase activity increases more rapidly than does
      elongation rate.Incubation of the seedlings in solutions of polyethyleneglycol
      inhibits the increase of both growth and invertase activity, the latter actually
      undergoing a decline, but causes no great change in the relative effect of GA(3).
      In presence of polyethyleneglycol GA(3) has however a relatively greater effect
      on invertase activity than on growth.Sugars in the incubation medium have no
      significant effect on growth and invertase activity in the epicotyl, except
      inhibition at relatively high concentrations.Cycloheximide, actinomycin D, and 5
      fluorodeoxyuridine (FUDR) inhibit both growth and the increase in invertase
      activity. Added during incubation cycloheximide causes complete inhibition of
      growth and a decrease in invertase activity with no appreciable lag phase. With
      actinomycin D and FUDR the inhibition occurs after lag periods of 2 to 3 and of
      at least 10 hours, respectively. Thus the increase in enzyme activity is very
      probably based on de-novo synthesis, and the enzyme is in a state of turnover
      during growth.The enzyme is present in soluble form in the cytoplasm, not firmly
      bound to any cell structures.

PMID- 16656886
TI  - Proteolytic activity in the genus ficus.
AB  - The latices of only 13 of a total of 46 species of Ficus examined contained
      appreciable proteolytic activity. Therefore, high proteolytic activity in the
      latex is not a distinguishing feature of the genus. The latex of F. stenocarpa
      had the highest specific activity followed closely by the latices of F. carica
      and F. glabrata. Latices of 6 species of Ficus were examined by chromatography on
      CM-cellulose and compared with the results obtained for 9 varieties of F. carica.
      All of the latices were found to contain multiple proteolytic enzymes.
      Chromatographically, the multiple enzyme components of the several varieties of
      F. carica were more similar than those of the several species examined. The
      latices of 16 varieties of F. carica were all different as determined by free
      boundary electrophoresis although the specific proteolytic activity of the
      latices was reasonably constant.

PMID- 16656887
TI  - Cellular senescence, radiation damage to mitochondria, and the compensatory
      response in ripening pear fruits.
AB  - A compensatory response, viz. in vivo recovery from radiation damage to
      mitochondria, occurs in preclimacteric pear fruits (Pyrus communis L.) treated
      with ionizing radiation. The compensatory response is absent or markedly impaired
      in senescent fruits irradiated at or near the climacteric peak. Senescent cells
      failed to recover from harmful effects of radiation on: 1) mitochondrial yield,
      2) in vivo incorporation of amino acids into mitochondrial protein, and 3)
      mitochondrial respiratory control and ADP/O. A diminished response to "split
      dose" irradiation and a delayed rate of recovery confirmed the degeneracy and
      loss of compensatory power with cell age.A loss of restorative activity,
      especially in mitochondria that supply the cell with essential energy, may
      underlie the more obvious signs of cumulative stress that accompany cellular
      senescence. Use of ionizing radiation as an investigative tool and the molecular
      implications of radiation damage, recovery, and cellular senescence are
      discussed.

PMID- 16656888
TI  - Pathway of Uridine Diphosphate N-Acetyl-d-Glucosamine Biosynthesis in Phaseolus
      aureus.
AB  - Studies with extracts obtained from mung beans (Phaseolus aureus) showed that UDP
      N-acetyl d-glucosamine is formed from d-fructose 6-phosphate by a series of the
      following enzymic reactions: [Formula: see text]UDP-N-acetyl-d-glucosamine
      inhibits the first reaction in the multistep pathway leading to its biosynthesis.

PMID- 16656889
TI  - Characterization of energy-dependent ca transport in maize mitochondria.
AB  - Experimental conditions which optimize both substrate- and ATP-dependent Ca(2+)
      transport in corn (Zea mays) mitochondria have been determined. It has been found
      that a substrate (pyruvate + succinate) dependent, Pi independent, binding of
      Ca(2+) occurs. This reaction is very rapid and complete in less than 30 seconds.
      For massive accumulation of calcium, Pi is essential. Phosphate is accumulated
      along with the calcium and the ratio of Ca:Pi accumulated is about 1.6:1
      indicating the precipitation of hydroxyapatite inside the mitochondria.The
      activation energies and Michaelis constants for both the substrate- and ATP
      driven reactions have been determined. It has also been shown that the substrate
      driven system is more efficient in Ca(2+) accumulation than the ATP-driven
      system. This is partially due to the fact that Mg(2+) is essential for the ATP
      driven system but not for the substrate-driven system and that Mg(2+) acts as a
      strong competitor of Ca(2+) transport. The effect of other inorganic ions on
      Ca(2+) transport energized by both substrate and ATP were examined.The results
      lend support to the hypothesis that high energy intermediates of oxidative
      phosphorylation participate directly in Ca(2+) binding and transport in plant
      mitochondria.

PMID- 16656890
TI  - Effect of substrate salinity on the ability for protein synthesis in pea roots.
AB  - THE EFFECT OF SALINITY ON INCORPORATION OF AMINO ACIDS INTO ROOT TIP PROTEIN IS
      APPARENTLY OF DUAL NATURE: in presence of salts the uptake is depressed and the
      normal metabolic pathways are disturbed. If the roots were grown at high salt
      concentration, uptake and incorporation are affected even if they are carried out
      in the absence of salt. NaCl and Na(2)SO(4) affect uptake, incorporation, and
      metabolism of (14)C leucine in different ways. There are also preliminary
      indications that in pea roots grown at different types of salinity, different
      proteins may be synthesized. Kinetin was found to inhibit incorporation of amino
      acids into non stressed and Na(2)SO(4) stressed roots, but promotes uptake and
      incorporation of amino acids into protein in NaCl stressed tissue. It seems that
      there are some pronounced differences between the effects of NaCl and Na(2)SO(4)
      salinities on the metabolism of pea root tissue.

PMID- 16656891
TI  - l-Phenylalanine Ammonia-Lyase Activity During Germination of Phaseolus vulgaris.
AB  - l-Phenylalanine ammonia-lyase (PAL) activity develops in excised bean axes after
      approximately 5 hours of incubation and reaches a maximum level after 14 hours of
      incubation. Light does not affect the development of activity, but puromycin,
      cycloheximide, actinomycin D, and 5-fluorouracil inhibit.During this period of
      incubation both d- and l-p-fluorophenylalanine stimulate fresh weight increase
      and both inhibit the development of PAL activity. Neither l- nor d-phenylalanine
      stimulates fresh weight increase while the former inhibits development of PAL
      activity and the latter has no effect. Neither d isomer is deaminated while l-p
      fluorophenylalanine is deaminated at about one-half the rate of l-phenylalanine.
      It is suggested that fluorophenylalanine does not stimulate the fresh weight
      increase by its effects on the phenolics pathway.Trans-cinnamic acid was found to
      inhibit both the development of PAL activity and the in vitro deamination of l
      phenylalanine. Various hydroxycinnamic acids, although inhibiting the development
      of PAL activity, had little or no effect on the in vitro deamination of l
      phenylalanine.No tyrosine ammonia-lyase activity was found in the axes and l
      tyrosine had no effect on the in vitro deamination of l-phenylalanine.The pattern
      of PAL development in intact seedlings differs markedly from that which occurs in
      the excised axes, although light also has no effect on the course of activity.

PMID- 16656892
TI  - Enzymes of glyoxylate in conifers.
AB  - The high level of lipids in seeds of some species of conifers suggested that the
      glyoxylate cycle might have a role in conifer seed metabolism.Six species (Pinus
      pinea, Pinus pinaster, Pinus canariensis, Pinus strobus, Abies alba, and
      Cupressus sempervirens) were investigated for their lipid content and malate
      synthase and isocitrate lyase level. The fatty acid composition of the
      triglyceride fraction was also investigated. The correlation between lipid
      content of germinating seed with the presence of the cycle was confirmed. The
      enzymes of the glyoxylate cycle were not detected in Cupressus sempervirens where
      the lipid content is very low.

PMID- 16656893
TI  - Photorespiration in Green Plants During Photosynthesis Estimated by Use of
      Isotopic CO(2).
AB  - Photosynthetic re-absorption of photorespired CO(2) causes underestimation in
      measured photorespiration and turnover rate of the substrate for
      photorespiration. Actual values of photorespiration exceed the measured by a
      factor greater than 1 + R'(w)/r(p) + [C(L)](x)/(r(p).L(x)). (R'(w) and r(p) are
      the partial resistances to CO(2) uptake between atmosphere, mesophyll evaporating
      surface, and photosynthetic sink, respectively; L(x) is the measured flux of
      photorespired CO(2) and [C(L)](x) is the ambient conc of photorespired CO(2)). In
      8 species, 1 + R'(w)/r(p) alone amounted to a correction ranging between 148% and
      233%.

PMID- 16656894
TI  - Inhibition of apple ripening by succinic Acid, 2,2-dimethyl hydrazide and its
      reversal by ethylene.
AB  - Ripening of McIntosh apples (Malus sylvestris L.) was delayed by treatments of
      succinic acid 2,2-dimethyl hydrazide (B-9) applied 2 weeks after bloom. The
      extent of retardation was dependent on concentration to 7.4 x 10(-2)m, at which
      level complete inhibition of ripening occurred under the conditions applied. The
      onset of the respiratory climacteric and fruit firmness changes were factors used
      to assess ripening.The inhibitory effect of B-9 was counteracted by 100 ppm of
      ethylene. This counteraction was independent of B-9 concentration or
      chronological age of fruit during the period of July 4 to September 20, 1967. The
      data suggest that B-9 suppresses ethylene biosynthesis or action within the fruit
      and that this suppression is not related to fruit maturity.

PMID- 16656895
TI  - Effects of salt secretion on psychrometric determinations of water potential of
      cotton leaves.
AB  - Thermocouple psychrometers gave lower estimates of water potential of cotton
      leaves than did a pressure chamber. This difference was considerable for turgid
      leaves, but progressively decreased for leaves with lower water potentials and
      fell to zero at water potentials below about -10 bars. The conductivity of
      washings from cotton leaves removed from the psychrometric equilibration chambers
      was related to the magnitude of this discrepancy in water potential, indicating
      that the discrepancy is due to salts on the leaf surface which make the
      psychrometric estimates too low. This error, which may be as great as 400 to
      500%, cannot be eliminated by washing the leaves because salts may be secreted
      during the equilibration period. Therefore, a thermocouple psychrometer is not
      suitable for measuring the water potential of cotton leaves when it is above
      about -10 bars.

PMID- 16656896
TI  - Studies on Auxin Protectors. V. On the Mechanism of IAA Protection by Protector-I
      of the Japanese Morning Glory.
AB  - The mechanism of auxin protection by auxin protector-I (Pr-I) of the Japanese
      morning glory was studied in vitro. Four lines of evidence indicate that Pr-I
      acts as a strong reductant which prevents the peroxidase-catalyzed oxidation of
      IAA: 1) The kinetics of the reaction are best explained on this basis. 2) The Pr
      I-induced lag preceding auxin destruction by peroxidase is completely eliminated
      by a strong oxidant such as H(2)O(2) at a concentration which does not
      appreciably affect the reaction rate. 3) Strong organic reductants mimic the Pr-I
      induced lag. And 4) when the reaction rate is altered by varying the
      concentrations of the reactants, or the temperature, the length of the Pr-I
      induced lag varies inversely with the reaction rate.

PMID- 16656897
TI  - Protein synthesis in relation to ripening of pome fruits.
AB  - Protein synthesis by intact Bartlett pear fruits was studied with ripening as
      measured by flesh softening, chlorophyll degradation, respiration, ethylene
      synthesis, and malic enzyme activity. Protein synthesis is required for normal
      ripening, and the proteins synthesized early in the ripening process are, in
      fact, enzymes required for ripening. (14)C-Phenylalanine is differentially
      incorporated into fruit proteins separated by acrylamide gel electrophoresis of
      pome fruits taken at successive ripening stages. Capacity for malic enzyme
      synthesis increases during the early stage of ripening. Fruit ripening and
      ethylene synthesis are inhibited when protein synthesis is blocked by treatment
      with cycloheximide at the early-climacteric stage. Cycloheximide became less
      effective as the climacteric developed. Ethylene did not overcome inhibition of
      ripening by cycloheximide. The respiratory climacteric is not inhibited by
      cycloheximide. It is concluded that normal ripening of pome fruits is a highly
      coordinated process of biochemical differentiation involving directed protein
      synthesis.

PMID- 16656898
TI  - Metabolic Changes in Excised Fruit Tissue. IV. Changes Occurring in Discs of
      Apple Peel During the Development of the Respiration Climacteric.
AB  - It is shown that a sequential development of a series of enzyme systems occurs in
      the peel of the apple as the respiration climacteric develops in the whole fruit.
      The sequence of development of these systems, i.e. acetate incorporation into
      lipid, production of ethylene, incorporation of amino acid into protein and,
      finally, the decarboxylation of added malate (malate effect) is the same as that
      shown earlier for the short term (24 hr) aging of peel discs from pre-climacteric
      apples. As these systems appear in the initial discs from fruit passing through
      the climacteric they gradually cease to increase during the 24 hour aging period.
      Uptake studies show that none of the changes in these systems can be due solely
      to changes in the permeability of the tissue over the climacteric period. On the
      basis of these results it is tentatively suggested that the aging of discs from
      pre-climacteric tissue might provide a model system for a detailed study of the
      physiological and biochemical changes occurring during the climacteric of apple
      fruits.

PMID- 16656899
TI  - Biosynthesis of cytidine diphosphate diglyceride by cauliflower mitochondria.

PMID- 16656900
TI  - Is Riboflavin the Photoreceptor in the Induction of Two-dimensional Growth in
      Fern Gametophytes?

PMID- 16656901
TI  - Growth Physics in Nitella: a Method for Continuous in Vivo Analysis of
      Extensibility Based on a Micro-manometer Technique for Turgor Pressure.
AB  - THE VIEW THAT THE PLANT CELL GROWS BY THE YIELDING OF THE CELL WALL TO TURGOR
      PRESSURE CAN BE EXPRESSED IN THE EQUATION: rate = cell extensibility x turgor.
      All growth rate responses can in principle be resolved into changes in the 2
      latter variables. Extensibility will relate primarily to the yielding properties
      of the cell wall, turgor primarily to solute uptake or production. Use of this
      simple relationship in vivo requires that at least 2 of the 3 variables be
      measured in a growing cell. Extensibility is not amenable to direct measurement.
      Data on rate and turgor for single Nitella cells can, however, be continuously
      gathered to permit calculation of extensibility (rate/turgor). Rate is accurately
      obtained from measurements on time-lapse film. Turgor is estimated in the same
      cell, to within 0.1 atm or less, by measurement of the ability of the cell to
      compress gas trapped in the closed end of a capillary the open end of which is in
      the cell vacuole. The method is independent of osmotic equilibrium. It operates
      continuously for several days, over a several fold increase in cell length, and
      has response time of less than one minute. Rapid changes in turgor brought on by
      changes in tonicity of the medium, show that extensibility, as defined above, is
      not constant but has a value of zero unless the cell has about 80% of normal
      turgor. Because elastic changes are small, extensibility relates to growth. Over
      long periods of treatment in a variety of osmotica the threshold value for
      extensibility and growth is seen to fall to lower values to permit resumption of
      growth at reduced turgor. A brief period of rapid growth (5x normal) follows the
      return to normal turgor. All variables then become normal and the cycle can be
      repeated. The cell remains essentially at osmotic equilibrium, even while growing
      at 5x the normal rate. The method has potential for detailed in vivo analyses of
      "wall softening."

PMID- 16656902
TI  - The acetylene-ethylene assay for n(2) fixation: laboratory and field evaluation.
AB  - The methodology, characteristics and application of the sensitive C(2)H(2)
      C(2)H(4) assay for N(2) fixation by nitrogenase preparations and bacterial
      cultures in the laboratory and by legumes and free-living bacteria in situ is
      presented in this comprehensive report. This assay is based on the N(2)ase
      catalyzed reduction of C(2)H(2) to C(2)H(4), gas chromatographic isolation of
      C(2)H(2) and C(2)H(4), and quantitative measurement with a H(2)-flame analyzer.
      As little as 1 mumumole C(2)H(4) can be detected, providing a sensitivity 10(3)
      fold greater than is possible with (15)N analysis.A simple, rapid and effective
      procedure utilizing syringe-type assay chambers is described for the analysis of
      C(2)H(2)-reducing activity in the field. Applications to field samples included
      an evaluation of N(2) fixation by commercially grown soybeans based on over 2000
      analyses made during the course of the growing season. Assay values reflected the
      degree of nodulation of soybean plants and indicated a calculated seasonal N(2)
      fixation rate of 30 to 33 kg N(2) fixed per acre, in good agreement with
      literature estimates based on Kjeldahl analyses. The assay was successfully
      applied to measurements of N(2) fixation by other symbionts and by free living
      soil microorganisms, and was also used to assess the effects of light and
      temperature on the N(2) fixing activity of soybeans. The validity of measuring
      N(2) fixation in terms of C(2)H(2) reduction was established through extensive
      comparisons of these activities using defined systems, including purified N(2)ase
      preparations and pure cultures of N(2)-fixing bacteria.With this assay it now
      becomes possible and practicable to conduct comprehensive surveys of N(2)
      fixation, to make detailed comparisons among different N(2)-fixing symbionts, and
      to rapidly evaluate the effects of cultural practices and environmental factors
      on N(2) fixation. The knowledge obtained through extensive application of this
      assay should provide the basis for efforts leading to the maximum agricultural
      exploitation of the N(2) fixation reaction.

PMID- 16656903
TI  - Role of gibberellins in stem elongation and flowering in radish.
AB  - The relationship among gibberellins, CCC, vernalization, and photoperiod in the
      flowering response of radish, Raphanus sativus L., cv. Miyashige-sofuto, was
      studied. The optimal condition for flowering was vernalization and a 16-hour
      photoperiod; GA(3) had no additional effect. Gibberellin A(3) (60 mug total) was
      not able to induce flowering in nonvernalized plants grown on 8-hour days, but it
      did increase the percentage of nonvernalized plants that flowered under long days
      from 60 to 100.Gibberellin content of vernalized seedlings increased within the
      first 24 hours after seedlings were transferred to the greenhouse. Content
      reached a peak in the first 4 days after transfer and thereafter remained
      constant. Essentially no gibberellin was found in 2 day-old non-vernalized
      (control) seedlings of comparable size to the vernalized ones. Gibberellin
      content in the controls reached a peak on the fourth day of growth in the
      greenhouse; thereafter, it decreased steadily.Bolting was inhibited slightly by
      CCC when applied during vernalization; it was almost completely inhibited when
      CCC was applied after seed vernalization. Extraction experiments revealed that
      CCC actually reduced the gibberellin content when applied during or after
      vernalization. The dwarfing agent, however, had essentially no effect on
      flowering. We concluded that gibberellins likely play a direct role in bolting of
      ;Miyashige-sofuto' radish, but probably are not directly functional in initiating
      flowering.

PMID- 16656904
TI  - Carbon-14 Distribution in Carbohydrates of Immature Zea mays. Kernels Following
      CO(2) Treatment of Intact Plants.
AB  - Shortly after Zea mays L. plants were exposed to (14)CO(2), most of the
      radioactivity in the kernel occurred in the free monosaccharides, glucose and
      fructose. Later the proportion of (14)C in sucrose increased and that in the
      monosaccharides declined. These data have been interpreted as showing that the
      translocated sugar is hydrolyzed prior to or during its movement into the storage
      cells of the endosperm. This hydrolysis appears to occur in the "pedicel region"
      of the kernel. After entry into the endosperm tissue, sucrose was rapidly
      resynthesized from the monosaccharides prior to its utilization in starch
      synthesis.

PMID- 16656905
TI  - Metabolism of cytidine and uridine in bean leaves.
AB  - The metabolism of cytidine-2-(14)C and uridine-2-(14)C was studied in discs cut
      from leaflets of bean plants (Phaseolus vulgaris L.). Cytidine was degraded to
      carbon dioxide and incorporated into RNA at about the same rates as was uridine.
      Both nucleosides were converted into the same soluble nucleotides, principally
      uridine diphosphate glucose, suggesting that cytidine was rapidly deaminated to
      uridine and then metabolized along the same pathways. However, cytidine was
      converted to cytidine diphosphate and cytidine triphosphate more effectively than
      was uridine. Cytidine also was converted into cytidylic acid of RNA much more
      extensively and into RNA uridylic acid less extensively than was uridine.
      Azaserine, an antagonist of reactions involving glutamine (including the
      conversion of uridine triphosphate to cytidine triphosphate), inhibited the
      conversion of cytidine into RNA uridylic acid with less effect on its
      incorporation into cytidylic acid. On the other hand, it inhibited the conversion
      of orotic acid into RNA cytidylic acid much more than into uridylic acid. The
      results suggest that cytidine is in part metabolized by direct conversion to
      uridine and in part by conversion to cytidine triphosphate through reactions not
      involving uridine nucleotides.

PMID- 16656906
TI  - Phospholipid synthesis in aging potato tuber tissue.
AB  - The effect of activation ("aging") of potato tuber slices on their phospholipid
      metabolism was investigated. Aged slices were incubated with (14)C labeled
      choline, ethanolamine, methionine, serine, and acetate. In all cases, the
      incorporation of radioactivity into the lipid fraction increased with the length
      of time the slices were aged. This incorporation was shown to be true synthesis
      and not exchange between precursors and existing phospholipids.The increased
      incorporation of labeled choline into lipids was mainly due to an increase in its
      uptake by the tissue, the presence of actidione during aging prevented this
      increased uptake. The increase in the incorporation of labeled acetate into
      lipids resulted from the development of a fatty acid synthetase during aging. In
      the case of ethanolamine, both its uptake into the tissue and its incorporation
      into the lipid fraction increased.The phospholipids formed from these precursors
      were identified by paper and thin-layer chromatography. The major compound formed
      from choline was lecithin, while phosphatidylethanolamine and a small amount of
      lecithin were formed from ethanolamine.

PMID- 16656907
TI  - Some Properties of Phytochrome Isolated From Dark-grown Oat Seedlings (Avena
      sativa L.).
AB  - Phytochrome was partially purified from etiolated seedlings of Avena sativa L.
      Several properties of the red-absorbing (P(R)) and far-red absorbing (P(FR))
      forms of the pigment were compared. The 2 forms could not be shown to differ with
      respect to their sedimentation velocity in sucrose density gradients, elution
      volume from Sephadex G-200 columns, binding properties on calcium phosphate, or
      electrophoretic mobility. P(FR), however, was more labile than P(R) during
      precipitation with 50% ammonium sulfate. Sephadex G-200 elution diagrams obtained
      with fresh phytochrome preparations revealed 2 components of different molecular
      weights, 1 roughly 180,000, and 1 roughly 80,000. Native phytochrome had an
      absorption spectrum in vivo showing an absorption maximum for P(R) of 667 nm.
      Both the large and small forms of phytochrome mentioned above can be maintained
      with an absorption maximum for P(R) of 667 nm. However, allowing them to remain
      for several hours as P(FR), even at 4 degrees , shifted this peak to 660 nm. The
      protein conformational change during phytochrome transformation may be quite
      small, though the various comparative techniques used do not strictly rule out a
      fairly large one. The need for maintaining the pigment as P(R) during all steps
      of purification, but particularly during ammonium sulfate precipitation is
      underscored.

PMID- 16656908
TI  - Abscission: the role of ethylene, ethylene analogues, carbon dioxide, and oxygen.
AB  - Ethylene was the most effective abscission accelerant examined, with decreasing
      activity shown by propene, carbon monoxide, acetylene, vinyl fluoride, 1-butene,
      and 1,3-butadiene. Carbon dioxide inhibited abscission, but its effect was
      overcome by ethylene. Oxygen was required for abscission as an electron acceptor
      for respiration and not as a potentiator or activator of the ethylene attachment
      site. The molecular requirements for abscission were similar to those shown by
      other workers for other biological processes under the influence of ethylene.

PMID- 16656909
TI  - Kinetically distinguishable populations of phytochrome.
AB  - Two or more kinetically distinguishable populations of phytochrome molecules were
      observed in living tissues of oat, pea, maize, and cauliflower, as well as in
      extracts of oat. At least 3 different populations occurred in cauliflower
      florets, while 2 were observed in each of the other species. In extracted oat
      phytochrome, the relative proportions of the 2 forms remained constant during
      successive stages of purification. The physiological significance of this
      multiplicity of forms remains unclear.

PMID- 16656910
TI  - Levels of phosphate esters in spirodela.
AB  - The duckweed Spirodela oligorrhiza was grown in sterile nutrient solutions that
      contained 1 mm phosphate-(32)P at various specific activities. In solutions with
      activities higher than 2 muc per mumole per ml, plant growth was inhibited after
      a time, and the physical appearance of the plants was affected. The critical
      level of radiation, at which growth was first affected, corresponded to 5
      kilorads.Plants were grown for 9 days (5 generations) in a culture solution
      containing phosphate at 0.5 muc per mumole per ml (radiation load approx 0.5
      kilorads) so that all phosphorus-containing materials in the tissue became
      uniformly labeled. The various radioactive compounds were extracted,
      chromatographed, identified, and their radioactivity was measured. From this
      radioactivity plus the specific activity of the supplied phosphate, the amount of
      each compound was calculated. The data constitute a complete balance-sheet for
      phosphorus in a plant tissue. The identity of 98% of the phosphorus in the tissue
      was determined. Inorganic phosphate (32,700 mmumoles/g fr wt) was the predominant
      phosphorus-containing compound; RNA (5100 mmumoles P/g fr wt) was the main
      organic phosphate; phosphatidyl choline (1600 mmumoles/g fr wt) was the main
      phospholipid, and glucose-6-phosphate (500 mmumoles/g fr wt) the main acid
      soluble phosphate ester. Amounts of other phosphorus compounds are given.

PMID- 16656911
TI  - Effect of phosphorus deficiency on levels of phosphorus compounds in spirodela.
AB  - When Spirodela plants are transferred to a phosphate-deficient medium, growth
      slows down immediately, and ceases after 14 days. During this time, inorganic
      phosphate content falls from 30 to 0.7 mumoles/g fresh weight of tissue,
      phosphate ester content from 3.5 to 0.6 mumoles/g, phospholipid content from 3.5
      to 1.2 mumoles/g, and residual phosphate (mainly RNA) content from 7.5 to 2.0
      mumoles/g. Relative proportions of the various phosphate esters, and relative
      proportions of the various phospholipids, are not markedly affected by phosphate
      deficiency. Turnover rates of phosphate esters are somewhat higher in phosphate
      deficient tissue. In control tissue, inorganic phosphate is present in 2 pools; a
      metabolic (12%) and a non-metabolic pool (88%). In phosphate-deficient tissues,
      most of the inorganic phosphate (>90%) is in the metabolic pool. Non-metabolic
      phosphate is presumably stored in the vacuole, and is not readily accessible to
      the tissue, so that growth normally occurs at the expense of external phosphate.
      During deficiency, growth is limited by the rate at which phosphate can be
      transported through the tonoplast and tissue to the growing point. Growth ceases
      when the supply of non-metabolic phosphate is exhausted. Metabolic phosphate is
      presumably located in the cytoplasm: it can not be used for growth. Nor can the
      plant respond to deficiency by making some phosphorus compounds at the expense of
      others. In this respect, phosphorus deficiency and nitrogen deficiency are
      dissimilar.

PMID- 16656912
TI  - Light Induced Concentration Changes of ATP From Phycomyces Sporangiophores: A Re
      examination.

PMID- 16656913
TI  - The response of wild type male gametes of allomyces to sirenin.

PMID- 16656914
TI  - Auxin transport and conjugation in cotton explants.

PMID- 16656915
TI  - Continuity of the Chloroplast Membrane Systems in Zea mays L.
AB  - Ultrastructural studies of the chloroplasts of the normal, yellow-green, and pale
      green phenotypes of Zea mays L. indicate that the internal membrane system is
      continuous with the plastid envelop. The intramembraneous spaces, loculi, and
      fret channels are also continuous with inner component of the plastid envelop.
      High energy compounds or other photosynthates, formed in the grana or frets are
      thus separated from both stroma and cytoplasm by a single membrane, either the
      fret membrane or the outer component of the plastid envelop. Since this type of
      plastid ultrastructure is apparently found only in plants exhibiting the Hatch
      and Slack pathways of photosynthesis there may be a relation between plastid
      ultrastructure and the pathways of photosynthetic carbon fixation.

PMID- 16656916
TI  - Plant nucleases. I. Separation and purification of two ribonucleases and one
      nuclease from corn.
AB  - Three enzymes with ribonuclease activity, one of which also had deoxyribonuclease
      activity, have been isolated and partially purified from corn seeds and
      seedlings. The purification of Ribonuclease I from mature seed was previously
      reported. This enzyme has a pH optimum near 5.0, is loosely adsorbed to
      carboxymethyl-cellulose, and has a molecular weight of 23,000, determined by gel
      filtration.Ribonuclease II was isolated from the microsomes of corn roots, and
      was partially purified by gel filtration. It has a pH optimum plateau from 5.4 to
      7.0, and molecular weight of 17,000.Nuclease I hydrolyzes both RNA and DNA. It
      was isolated from the large particles of a corn root homogenate and was partially
      purified on a carboxymethyl-cellulose column. It has a pH optimum at 6.2 and a
      molecular weight of 31,000.The relative activities of the 3 enzymes for
      deoxyribonuclease and at pH 5 and pH 6.2 for ribonuclease may be used to
      characterize them during purification operations. Assays on homogenates of corn
      roots, and especially of the root tips, suggested that a fourth enzyme, which
      possesses deoxyribonuclease activity, is also present.

PMID- 16656917
TI  - Plant Nucleases. II. Properties of Corn Ribonucleases I and II and Corn Nuclease
      I.
AB  - A classification system is presented to distinguish 3 corn nucleases-Ribonuclease
      I, Ribonuclease II, and Nuclease I-which were described in the first paper of
      this series. The 2 ribonucleases are specific for RNA, are endonucleases, and
      liberate purine and pyrimidine cyclic nucleotides from dinucleotide
      monophosphates as well as from RNA. Ribonuclease I and II hydrolyze the purine
      cyclic nucleotides to 3'-nucleotides, while Ribonuclease II may also act on the
      pyrimidine cyclic nucleotides. Ribonuclease II is best characterized by its
      molecular weight of 17,000, by a higher pH optimum than Ribonuclease I, and by
      its absorption onto microsomes.Nuclease I is a partially purified endonuclease
      which produces 5'-nucleotides from RNA, DNA, and dinucleotide monophosphates. The
      same enzyme may also be a 3'-nucleotidase.The corn nucleases were compared with
      nucleases found in other plant species.

PMID- 16656918
TI  - The Differentiation of Pigmentation in Flower Parts, IV. Flavonoid Elaborating
      Enzymes From Petals of Impatiens balsamina s.
AB  - Extracts of the flower petals of Impatiens balsamina L. contain enzymes which
      catalyze the glycosylation of phenolic compounds. Enzymes have been extracted
      which glycosylate hydroquinone to arbutin and at least 3 different flavonols to
      the 3-monoglucoside. The hydroquinone glucosylating enzyme is similar to enzymes
      previously described except that it requires an unidentified low molecular weight
      cofactor. The glucosylation of flavonols follows normal enzyme kinetics; it
      requires a nucleotide diphosphate glucose donor for activity, and is made more
      evident by the presence of glucono-1:5-lactone, an inhibitor of endogenous
      glucosidases. It is suggested that the flavonol glucosylating enzyme acts
      naturally to glucosylate a precursor of both flavonols and anthocyanins to the 3
      monoglucoside. The only elaboration of an anthocyanin observed with petal
      extracts was an acylation of pelargonidin-3-monoglucoside.

PMID- 16656920
TI  - Calcium and Nodulation in Subterranean Clover (Trifolium subterraneum L.).
AB  - From a study of the effects of Ca ions on the nodulation of subterranean clover
      in flowing culture solutions it is concluded that root infection or nodule
      initiation has a higher Ca requirement than either nodule development or host
      plant growth in the presence of fixed nitrogen.Increasing Ca concentration from
      246 to 720 mum had no effect on growth of the host plant but increased the number
      of nodules from 7 to 24 per plant. Decreasing Ca concentration from 246 to 4 mum
      progressively decreased both plant growth and nodule numbers.It is suggested that
      nodule infection or initiation required higher solution concentration of Ca than
      nodule development since transferring plants after 10 days in lower Ca treatments
      to 720 mum Ca for 7 days did not increase nodule numbers above those on plants
      treated continuously at low Ca. Similarly transferring plants from 720 mum Ca to
      lower Ca treatments did not decrease nodule numbers much below those on plants
      grown continuously at 720 mum Ca even though growth was depressed. Once
      initiated, nodule development proceeded at concentrations of Ca too low for plant
      growth.The high Ca requirement for root infection or nodule initiation was not
      thought to be due to effects on survival or growth of Rhizobium and could not be
      related to effects of Ca on a number of relevant processes:-tap root length, root
      hair development, or lateral root initiation.

PMID- 16656919
TI  - Ribonuclease Activity Associated With Ribosomes of Zea mays.
AB  - At pH 6.5, a ribonuclease(s) is associated with ribosomes isolated from corn (Zea
      mays L.) and cannot be removed by repeated differential centrifugation or by
      sedimenting through the sucrose gradient. The enzyme is active under conditions
      favoring the maintenance of integrity of the ribosomes. Little or no latent
      ribonuclease appears to be present. The activity of the enzyme at pH 5.8 is
      stimulated by KCl and inhibited by polyvinyl sulfate, zinc, and bentonite.
      Deoxyribonuclease is also found on the particles.The enzyme can be removed from
      ribosomes by adsorption onto bentonite. Ribosomes are also adsorbed but to a much
      lesser extent at low bentonite concentrations. The enzyme is easily dissociated
      from ribosomes by raising the pH to 8.5, and readsorbed when the pH is
      lowered.The ribonuclease activity on ribosomes shows a sharp increase with cell
      age that parallels closely the increase in total activity in the homogenate. The
      ratio of activities of deoxyribonuclease to ribonuclease on ribosomes also
      changes with cell age and again the changes appear to reflect changes in the
      homogenate. It is suggested that most of the association of ribonuclease with
      corn ribosomes may not be meaningful in vivo and occurs only after the cells are
      ruptured.

PMID- 16656921
TI  - Lipids in grape roots in relation to chloride transport.
AB  - A comparison was made between the lipids of the roots of 5 grape rootstocks which
      differ markedly in the extent to which they permit chloride accumulation in
      leaves. Monogalactose diglyceride concentration was directly related to chloride
      accumulation in the leaves of the 5 rootstocks. Phosphatidylcholine and
      phosphatidylethanolamine were inversely related to chloride accumulation. The
      variety with the highest chloride accumulation contained an unusually small
      amount of sterols. A striking negative correlation between content of lignoceric
      acid and chloride accumulation was observed. The lignoceric acid concentration
      ranged from 11.9% in the rootstock with the lowest chloride accumulation to 0.8%
      in the rootstock with the highest chloride accumulation. This fatty acid was
      found mainly in the phosphatidylcholine and the phosphatidylethanolamine lipid
      fractions.

PMID- 16656922
TI  - Ion transport characteristics of grape root lipids in relation to chloride
      transport.
AB  - Ion transport properties of grape root lipids were measured as liquid-membrane
      permeability. Phosphatidylcholine exchanged chloride very slowly against
      carbonate and bicarbonate but more rapidly against nitrate, phosphate, and
      sulfate. Exchange of chloride against nitrate was rather low for the
      phosphatidylcholine and phosphatidylethanolamine lipid fractions; monogalactose
      diglyceride was by far the most effective chloride transporter studied.
      Comparison between the lipid composition of the roots of the 5 grape rootstocks
      and the chloride transport capacity of the specific membranes strongly suggests
      that, indeed, the chloride transport capacity of the lipids present in the
      membranes of the root cells accounts for the observed differences in chloride
      transport to the leaves. Whereas monogalactose diglyceride had a high chloride
      transport capacity, compared with phosphatidylcholine, the reverse was true for
      exchange of sodium against potassium. Thus, phosphatidylcholine has more the
      properties of a cation exchanger, and monogalactose diglyceride those of an anion
      transporter.

PMID- 16656923
TI  - Does ethylene mediate root growth inhibition by indole-3-acetic Acid?
AB  - The effects of ethylene and of indole-3-acetic acid (IAA) on growth of excised
      pea root sections have been compared under a variety of conditions. After 16
      hours treatment the inhibitory action of IAA is fully reversible on transfer of
      the root sections to IAA-free solutions. In contrast, inhibition by ethylene is
      almost totally irreversible. IAA inhibits growth from zero time; ethylene is
      generally without effect during the first 3 to 6 hours. The inhibitory action of
      ethylene is dependent on factors such as tissue age and solution composition
      which have no major effect on IAA inhibition. Ethylene production is enhanced by
      100 mum IAA, but conditions which reduce the rate of ethylene evolution 2 to 3
      fold at the same IAA concentration fail to affect the inhibitory action of IAA on
      elongation. It seems unlikely that ethylene can play more than a minor role in
      mediating inhibition of pea root growth by IAA.

PMID- 16656924
TI  - Translocation of assimilates and phosphate in detached bean leaves.
AB  - (14)C-assimilates were accumulated by the veins in the blades and transported
      basipetally into the petioles of detached leaves of Red Kidney bean (Phaseolus
      vulgaris L.). Neither process was greatly affected by mild moisture stress, age
      of fully enlarged leaves, or period in the dark prior to exposure to (14)CO(2).
      However, both vein loading and transport into petioles were greatly reduced by
      oxygen deficiency. The basipetal transport of (32)PO(4) also did not appear to be
      greatly reduced by 6 or 8 days of darkness prior to the application of phosphate
      (32)P, followed by a transport period of 1 day in the dark. Endothall at 5 x 10(
      3)m was effective in stopping basipetal flow of (32)P. It is considered that
      transport in leaves may be powered by forces in the plasmodesmata of the cell
      walls between the border parenchyma and phloem.

PMID- 16656925
TI  - Gas-liquid chromatography of trimethylsilyl derivatives of abscisic Acid and
      other plant hormones.
AB  - This paper describes a new method for qualitative and quantitative assay of
      abscisic acid and other acidic plant hormones, such as indoleacetic acid and the
      gibberellins, by the gas-liquid chromatography of their trimethylsilyl
      derivatives. Interfering substances in plant extracts were largely removed by
      preliminary column chromatography with carbon-celite and elution of the abscisic
      acid with 60% acetone, permitting direct determination of abscisic acid by gas
      liquid chromatography using a flame ionization detector. (A level of 0.65 mg/kg
      fr wt was found.) This method enables measurement of amounts of abscisic acid as
      low as 0.025 mug. In impure samples collected by gas-liquid chromatography the
      abscisic acid recovered could be measured quantitatively by use of its
      ultraviolet absorption maximum at 260 mmu.

PMID- 16656926
TI  - Oxido-Reduction States and Natural Homologue of Ubiquinone (Coenzyme Q) in
      Submitochondrial Particles From Etiolated Mung Bean (Phaseolus aureus) Seedlings.
AB  - A procedure for the isolation of submitochondrial particles in quantity from
      etiolated Mung bean (Phaseolus aureus) seedlings is described. Using a
      combination of acetone extraction and 2 systems of thin layer chromatography
      ubiquinone has been isolated. The isolated ubiquinone migrates coincident with
      authentic ubiquinone-10 in reversed phase thin layer partition chromatography,
      gives a positive Craven's test, and has oxidized and reduced spectra
      characteristic of ubiquinone. The quinone is partially reduced under steady-state
      electron transfer conditions with both succinate and NADH as substrates and is
      almost completely reduced under anaerobic conditions with either substrate. The
      concentration of ubiquinone in the particle is of the order of 4.4 mmumoles per
      mg particle protein, approximately equal to that found in similar
      submitochondrial particles from beef heart. It is tentatively concluded that
      ubiquinone-10 is a functional member of the mitochondrial electron transfer chain
      of Phaseolus aureus.

PMID- 16656927
TI  - Uptake of Carrier-free Cs by Ramalina reticulata.
AB  - The uptake of carrier-free (137)Cs by Ramalina reticulata Kremp. does not appear
      to be directly linked to metabolism. The results indicate the presence of a
      barrier to entry of (137)Cs. The barrier is stabilized by Ca ions. Removal of Ca
      by pretreatment of the tissue in monovalent salt solutions increases the uptake
      of (137)Cs. Uptake under anaerobiosis is also greater than normal, but in this
      case, Ca displaced from the barrier membrane is not lost from the tissue and
      normal permeability is rapidly re-established when aerobic conditions are
      restored. Under anaerobiosis Ca(2+) increases damage to the respiratory mechanism
      presumably by increasing retention of toxic products.

PMID- 16656928
TI  - On methods of isolation of active, tightly coupled mitochondria of wheat
      seedlings.
AB  - Tightly coupled mitochondria can be isolated from wheat seedlings 1) if young
      seedlings are used, 2) if the grinding medium is buffered and contains bovine
      serum albumin (BSA), 3) if the isolation procedure, including centrifugation is
      10 to 11 minutes long. Mitochondria isolated in this manner oxidize alpha
      ketoglutarate, malate and NADH. Respiratory control (R.C.) values are around 6,
      3, and 10, respectively. ADP:O values with those substrates are 4.0, 2.9, and
      1.7, respectively. Mitochondria are stable for 3 hours. It is suggested that the
      technique may be used for preparation of mitochondria for comparative studies
      since activities of these mitochondria are highly reproducible.

PMID- 16656929
TI  - delta-Aminolevulinic Acid Transaminase in Chlorella vulgaris.
AB  - An enzyme catalyzing the formation of delta-aminolevulinic acid by transamination
      of gamma,delta-dioxovaleric acid with l-alpha-alanine, l-glutamic acid, or l
      phenylalanine has been detected in extracts of Chlorella vulgaris. The activity
      of this enzyme does not appear to parallel changes in chlorophyll content in a
      Chlorella mutant which requires light for chlorophyll production. The role of
      this enzyme in delta-aminolevulinic acid metabolism in plants is not clearly
      understood.

PMID- 16656930
TI  - The isolation of spinach chloroplasts in pyrophosphate media.
AB  - A simplified procedure (involving disruption in sorbitol-pyrophosphate mixtures)
      permits the separation of spinach chloroplasts which retain the ability to
      catalyze the photosynthetic assimilation of carbon dioxide and its associated
      oxygen evolution.

PMID- 16656931
TI  - Photosynthesis by isolated chloroplasts, simultaneous measurement of carbon
      assimilation and oxygen evolution.
AB  - Photosynthetic carbon assimilation by isolated chloroplasts and its associated
      oxygen evolution were measured simultaneously in a single simplified reaction
      mixture. Each showed an initial lag prior to the attainment of the maximal rate
      and the photosynthetic quotient was unity during the period of illumination.
      Following illumination an oxygen uptake was observed in the dark which was not
      accompanied by any net release of newly fixed carbon dioxide.

PMID- 16656932
TI  - Species specificity in the biosynthesis of branched paraffins in leaves.
AB  - Isobutyrate-1-(14)C and l-isoleucine-U-(14)C fed through the petiole labeled the
      surface lipids of broccoli leaves, but the incorporation was much less than from
      straight chain precursors. Not more than one-third of the (14)C incorporated into
      the surface lipids was found in the C(29) paraffin and derivatives, whereas more
      than two-thirds of the (14)C from straight chain precursors are usually found in
      these compounds. The small amount of (14)C incorporated into the paraffin
      fraction was found in the n-C(29) paraffin rather than branched paraffins showing
      that the (14)C in the paraffin must have come from degradation products. Radio
      gas-liquid chromatography of the saturated fatty acids showed that, in addition
      to the n-C(16) acid which was formed from both branched precursors, isoleucine-U
      (14)C gave rise to branched C(15), C(17), and C(19) fatty acids, and isobutyrate
      1-(14)C gave rise to branched C(16) and C(18) acids. Thus the reason for the
      failure of broccoli leaf to incorporate branched precursors into branched
      paraffins is not the unavailability of branched fatty acids, but the absolute
      specificity of the system that synthesizes paraffins, probably the elongation
      decar-boxylation enzyme complex. Consistent with this view, no labeled branched
      fatty acids longer than C(19) could be found in the broccoli leaf. The branched
      fatty acids were also found in the surface lipids indicating that the epidermal
      layer of cells did have access to branched chains. Thus the paraffin synthesizing
      enzyme system is specific for straight chains in broccoli, but the fatty acid
      synthetase is not.

PMID- 16656933
TI  - Invertase inhibitors from red beet, sugar beet, and sweet potato roots.
AB  - Invertase inhibitors have been isolated and partially purified from red beets,
      sugar beets, and sweet potatoes. These inhibitors are thermolabile proteins with
      molecular weights of 18,000 to 23,000. They do not inhibit yeast and Neurospora
      invertases, but they are reactive with potato tuber invertase and other plant
      invertases with pH optima near 4.5. There are differences in reactivity of the
      inhibitors with some of the plant invertases, however. For most invertases, red
      beet and sugar beet inhibitors are most effective at pH 4.5 while sweet potato
      inhibitor is most effective at pH 5.

PMID- 16656934
TI  - Relationship Between Metabolism and the Lateral Transport of IAA in Corn
      Coleoptiles.
AB  - The lateral movement of IAA in coleoptiles of Zea mays has been investigated
      under aerobic and anaerobic conditions. The IAA-1-(14)C was supplied
      asymmetrically to the apical end of the segment. The results were as follows: A)
      In air more (14)C was found in the lower half of horizontal segments supplied
      with an upper donor than in the half opposite the donor in vertical segments. The
      enhanced lateral movement of (14)C in geotropically stimulated segments of corn
      coleoptiles under aerobic conditions has thus been confirmed. B) This increased
      lateral movement of (14)C in geotropically stimulated segments is greatly
      reduced, but is not completely abolished, under anaerobic conditions. C) The
      lateral movement of (14)C in vertical segments is significantly less under
      anaerobic conditions than in air. D) Under anaerobic conditions, the lateral
      movement of (14)C in horizontal segments can be reduced to the level found in
      vertical segments by pre-soaking the tissue in a 1 mm solution of the metabolic
      inhibitor sodium fluoride for 2 hours. The inhibitor has no effect on lateral
      movement of (14)C in vertical anaerobic segments. E) In air, sodium fluoride has
      no effect on the lateral movement of (14)C in either vertical or horizontal
      segments.On the assumption that the movement of (14)C reflects the movement of
      IAA, these results show that the enhanced polarized lateral movement of IAA
      observed in horizontal corn coleoptile segments is totally abolished only when
      both aerobic and anaerobic metabolism are arrested. In addition, there appears to
      be a small metabolically dependent component in the lateral movement of IAA in
      vertical segments supplied with an asymmetric donor in air.

PMID- 16656935
TI  - Abscisic Acid levels and seed dormancy.
AB  - Dormant seeds from Fraxinus species require cold-temperature after-ripening prior
      to germination. Earlier, we found that abscisic acid (ABA) will inhibit
      germination of excised nondormant embryos and that this can be reversed with a
      combination of gibberellic acid and kinetin. Using Milborrow's quantitative
      "racemate dilution" method the ABA concentration in 3 types of Fraxinus seed and
      pericarp were determined. While ABA was present in all tissues, the highest
      concentration was found in the seed and pericarp of dormant F. americana. During
      the chilling treatment of F. americana the ABA levels decreased 37% in the
      pericarp and 68% in the seed. The ABA concentration of the seed of the nondormant
      species, F. ornus, is as low as that found in F. americana seeds after cold
      treatment. Experiments with exogenously added ABA solutions indicate that it is
      unlikely that the ABA in the pericarp functions in the regulation of seed
      dormancy. However, the ABA in the seed does seem to have a regulatory role in
      germination.

PMID- 16656936
TI  - Synthesis and Stability of Chloroplast Ribosomal-RNA's.
AB  - The chloroplast ribosomal-RNAs (1.1 x 10(6) and 0.56 x 10(6) mol wt) are
      synthesized in the normal ratio of 2:1. The non-ribosomal distribution observed
      after extraction and fractionation results from the lability of the 1.1 x 10(6)
      component, and a correction for this breakdown can be applied in certain cases.
      Newly synthesized 1.1 x 10(6) RNA is more stable than the older accumulated 1.1 x
      10(6) RNA. Accumulation of the chloroplast RNA during growth of radish cotyledons
      occurs at a later time than the accumulation of cytoplasmic RNA, and its turnover
      is much less than that of the cytoplasmic ribosomal-RNA.

PMID- 16656937
TI  - Effect of 2,4-dichlorophenoxyacetic Acid on the cytokinin requirement of soybean
      cotyledon and tobacco stem pith callus tissues.

PMID- 16656938
TI  - An electron donor system for nitrogenase-dependent acetylene reduction by
      extracts of soybean nodules.

PMID- 16656939
TI  - Cytochrome oxidase of cactus.

PMID- 16656940
TI  - Inhibition of Gibberellic Acid-induced Germination by Abscisic Acid and Reversal
      by Cytokinins.

PMID- 16656941
TI  - Tests Whether a Head to Head Condensation Mechanism Occurs in the Biosynthesis of
      n-Hentriacontane, the Paraffin of Spinach and Pea Leaves.

PMID- 16656942
TI  - Changes in enzymatic activities in etiolated bean seedling leaves after a brief
      illumination.
AB  - The phytochrome controlled increase in total protein in the primary leaf pair of
      etiolated bean (Phaseolus vulgaris var. Black Valentine) seedlings, which occurs
      during growth in the dark subsequent to a brief illumination, was investigated.
      Enzymes from the chloroplasts, the mitochondria, and the soluble cytoplasm all
      increase in total activity after the illumination.The total protein and the
      ribulose carboxylase increases are not inhibited by FUdR, an inhibitor of DNA
      synthesis. Cycloheximide, an inhibitor of protein synthesis, applied at a time
      when the ribulose carboxylase activity increase has already commenced, blocks
      further increase. It was concluded that the total protein and the enzyme
      increases in the leaf are the result of increases in the per cell levels.The
      initial brief illumination is saturating, but 40 minutes later the seedlings have
      acquired the ability to respond to a second brief illumination. The rate of
      increase in ribulose carboxylase activity in seedlings that have been illuminated
      twice is greater than the rate in seedlings that have been illuminated only
      once.Far-red light prevents further increase in enzyme activity 48 hours after
      the initial illumination. There is a lag period interposed between the time of
      illumination with far-red light and the time at which the seedlings show the
      greatest effect of far-red light. It was concluded that the phytochrome influence
      on protein synthesis is not at the terminal steps.

PMID- 16656943
TI  - Oxygen evolution and the permeability of the outer envelope of isolated whole
      chloroplasts.
AB  - A rapid oxygraph method of studying the permeability of the envelope of isolated
      chloroplasts was used. The outer envelope of aqueously isolated whole spinach
      (Spinacia oleracea L.) chloroplasts in buffer is readily permeable to 3
      phosphoglyceric acid, which induces an immediate light dependent oxygen
      evolution. This light dependent oxygen evolution was completely eliminated by
      swelling these plastids in an osmotically dilute solution. Exogenous adenosine
      diphosphate, but not inorganic phosphate, strongly stimulated this oxygen
      evolution. This indicated that the chloroplast envelope is relatively permeable
      to adenosine diphosphate.Oxygen evolution and swelling studies indicated that the
      chloroplast envelope is relatively impermeable to NADP and to ferredoxin.A method
      is described whereby the percent of whole chloroplasts present in a chloroplast
      preparation may be rapidly estimated.

PMID- 16656944
TI  - Comparison of upward and downward translocation of C from a single leaf of
      sunflower.
AB  - When single leaves attached at a given node were allowed to carry on
      photosynthesis in (14)CO(2) for 30 min, younger plants showed a higher proportion
      of upward translocation than did older plants. Downward translocation of (14)C
      photosynthate was stimulated by ATP pre-treatment of the translocating leaf,
      while upward translocation was not affected by ATP. A similar phenomenon was
      observed in the translocation of (14)C-sucrose infiltrated into a leaf with or
      without ATP. Downward translocation of photosynthate was inhibited by DNP pre
      treatment of a fed leaf. Upward translocation, however, was not affected by DNP.
      Thirty min after infiltration of (14)C-glucose into a leaf, almost all the (14)C
      translocated upwards was found to be in the form of glucose, while a great part
      of the (14)C translocated downwards was in the form of sucrose. In the case of
      translocation of infiltrated (14)C-sucrose, (14)C found both above and below the
      fed leaf was mainly in the form of sucrose.

PMID- 16656945
TI  - Characteristics of a virescent cotton mutant.
AB  - The virescent cotton (Gossypium hirsutum) mutant described here differs from
      normal cultivated cotton by a single mutation in the nucleus. The mutant exhibits
      nuclear control of chlorophyll and carotenoid development. Young leaves are
      distinctly yellow and become green with age. There is no unusual photometabolism
      of (14)CO(2) or (14)C-acetate in this mutant. It is probable that the nuclear
      virescent mutation is in a locus concerned with making structural units. The
      yellow leaves do show a high photosynthetic capacity on a chlorophyll basis. At
      saturating light intensity the rate of CO(2) fixation is 8 fold higher than the
      green control leaves. Thus, impaired pigment synthesis which could be lethal is
      offset by a high photosynthetic capacity in the virescent leaves.

PMID- 16656946
TI  - Seasonal Course of Photosynthesis, Respiration, and Distribution of C in Young
      Pinus resinosa Trees as Related to Wood Formation.
AB  - Rates of net photosynthesis and dark respiration, and distribution of (14)C were
      determined for new (current season's) and old (previous season's) needles at 10
      times during the seasonal development of young Pinus resinosa Ait. trees. The
      seasonal changes in these factors associated with the development of the new
      shoot were related to known seasonal patterns of wood formation.Net
      photosynthesis per gram of needle dry weight (photosynthetic efficiency) was
      maximum in the old needles at the time of first new needle elongation; at the
      same time translocation of (14)C from old to new needles was greatest.
      Photosynthetic efficiency of new needles was maximum at the end of the period of
      rapid new needle elongation, when the new needles also began exporting much
      greater quantities of (14)C to other plant parts. In particular, the amount
      translocated from the new needles to the stem was greatly increased. At this time
      thick-walled xylem cells were first observed in the stem.These results, together
      with those of previous studies, indicate that the production of thick-walled
      xylem tracheids normally associated with latewood is physiologically correlated
      with maturation of the current season's needles. Because there is a lesser demand
      for photosynthate in the new shoot and a high rate of photosynthesis in the whole
      plant at the time of new needle maturity, a sharply increased amount of
      photosynthate becomes available for wall synthesis by cambial derivatives.

PMID- 16656947
TI  - Hydroxyproline Formation and Its Relation to Auxin-induced Cell Elongation in the
      Avena Coleoptile.
AB  - A study has been made of the effects on hydroxyproline formation of 4 factors
      that influence the rate of cell elongation in the Avena coleoptile; auxin,
      sugars, an external osmoticum, and actinomycin D. Hydroxyproline formation is
      increased by a combination of auxin and sucrose, but is affected to a much lesser
      extent by either factor alone. Its formation is inhibited by an external
      osmoticum but is scarcely affected by actinomycin D. The lack of correlation
      between the amount of hydroxyproline synthesis and the growth rate suggests that
      hydroxyproline formation is not involved in the actual process of wall loosening.
      It is suggested, instead, that if the wall is to retain its capacity for rapid
      extension, those hemicelluloses which are incorporated into it by intussusception
      rather than by apposition must be attached to a hydroxyproline-protein.

PMID- 16656948
TI  - Labeling pattern of translocated stachyose in squash.
AB  - One mature blade of each squash plant was continuously labeled with (14)CO(2) for
      15, 30, or 70 minutes in light. The ethanol soluble materials from serial
      sections of petioles were extracted and separated by paper chromatography. The
      ratios of label in the various components of this fraction were determined.
      Stachyose, which contained the major portion of the label of this fraction, was
      hydrolyzed and the resultant hydrolysate was separated by paper chromatography.
      Specific activities of the hexoses derived from stachyose were determined. It was
      found that the glucose and fructose moieties of stachyose became labeled at the
      same rates; however, the galactose moiety became labeled more rapidly.

PMID- 16656949
TI  - Fat Metabolism in Higher Plants XXXVI: Long Chain Fatty Acid Synthesis in
      Germinating Peas.
AB  - A low lipid, high starch containing tissue, namely cotyledons of germinating pea
      seedlings was examined for its capacity to synthesize fatty acid. Intact tissue
      slices readily incorporate acetate-(14)C into fatty acids from C(16) to C(24).
      Although crude homogenates synthesize primarily 16:0 and 18:0 from malonyl CoA,
      subsequent fractionation into a 10,000g pellet, a 10(5)g pellet and supernatant
      (soluble synthetase) revealed that the 10(5)g pellet readily synthesizes C(16) to
      C(28) fatty acids whereas the 10,000g and the supernatant synthesize primarily
      C(16) and C(18). All systems require acyl carrier protein (ACP), TPNH, DPNH if
      malonyl CoA is the substrate and ACP, Mg(2+), CO(2), ATP, TPNH, and DPNH if
      acetyl CoA is the substrate. The cotyledons of germinating pea seedlings appear
      to have a soluble synthetase and 10,000g particles for the synthesis of C(16) and
      C(18) fatty acid, and 10(5)g particles which specifically synthesize the very
      long chain fatty acid from malonyl CoA, presumably via malonyl ACP.

PMID- 16656950
TI  - Rotational streaming in fiber cells and its role in translocation.
AB  - All visible protoplasmic streaming in sections of various plant stems was
      reversibly stopped by 2,4-dinitrophenol (DNP). Sections contained epidermal,
      cortical, and fiber cell types. Cells treated with DNP retained their
      semipermeability as evidenced by their plasmolysis in sucrose solutions. Washing
      out the DNP resulted in the rapid resumption of protoplasmic streaming in all 3
      cell types. Both the rate of movement of sodium fluorescein and the shape of the
      advancing dye front were greatly altered by DNP treatment. Dye transport was
      decreased in the fibers and little affected in cortical cells. The results
      suggest that rotational streaming accelerates the translocation of soluble
      substances in fiber cells.

PMID- 16656951
TI  - Effect of N-tris (Hydroxymethyl) Methylglycine and N-2-Hydroxyethyl-piperazine-N'
      2-Ethanesulfonic Acid Buffers on Linolenic Acid as a Substrate for Flaxseed
      Lipoxidase.
AB  - The delay in, or loss of, flaxseed lipoxidase activity in N-tris (hydroxymethyl)
      methylglycine and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffers
      with linolenic acid as a substrate appears due to an alteration of the lipid
      micelle. Flaxseed lipoxidase activity is dependent on the ionic strength of the
      assay solution. These effects are not observed with linoleic acid as substrate.
      The influence of these 2 buffers on linolenic acid micelles may have a direct
      bearing on recent reports of chloroplast structure and activity in these buffers.

PMID- 16656952
TI  - A Study of Plastoquinones in Photochemical Reactions in the Chloroplasts of
      Euglena gracilis Strain Z.
AB  - Plastoquinone-9 (PQ-9) was isolated from the chloroplasts of Euglena gracilis
      Strain Z and spinach. The functional involvement and the structural specificity
      of PQ-9 in photochemical reactions was investigated in the isolated chloroplasts
      of Euglena gracilis. It was found that PQ-9 was required for both photoreduction
      of ferricyanide and photosynthetic phosphorylation in Euglena chloroplasts. The
      structural integrity of PQ-9 was not required to the same degree in the 2
      photochemical reactions. Photosynthetic phosphorylation seemed to require the
      entire molecular structure of PQ-9 for the activity, whereas shortening in
      isoprenoid chain and modification of quinoid nucleus of PQ-9 do not seem to alter
      the photoreduction activity significantly. Addition of PQ-9 to the lyophilized
      Euglena chloroplasts inhibited the photoreduction of ferricyanide significantly,
      while it stimulated photosynthetic phosphorylation activity.

PMID- 16656953
TI  - Effect of Infection by Hypomyces solani f. sp. Cucurbitac on Apparent Free Space,
      Cell Membrane Permeability, and Respiration of Squash Hypocotyls.
AB  - Initial symptoms and increases in respiration, apparent free space, and rate of
      leakage of amino acids occurred concomitantly in squash (Cucurbita maxima Dcne)
      hypocotyls infected by Hypomyces solani f. sp. cucurbitae Snyd. and Hans. Young,
      rapidly expanding lesions had greater respiratory rates and apparent free space
      than comparable tissues from healthy plants.Hypocotyl tissues above (1-45 mm)
      lesions possessed greater endogenous respiratory rates (2-3 times) and lower
      respiratory quotients than similar tissues from healthy plants. But no
      differences were found in membrane permeability to nonelectrolytes and water and
      in apparent free space between cells above lesions and healthy hypocotyls.Host
      cells contiguous to fungal hyphae at lesion margins were completely permeable to
      solutes and failed to accumulate neutral red or exhibit cyclosis.

PMID- 16656954
TI  - Biological Activity of a Phytotoxic Glycopeptide Produced by Corynebacterium
      sepedonicum.
AB  - A purified toxic glycopeptide from Corynebacterium sepedonicum (Speick.) Dows.,
      possesses the capacity to wilt plant cuttings. The toxin induces a rapid general
      flaccidity in stem tissues followed by a leaf wilt making its effects
      significantly different from that induced by high molecular weight substances
      (dextrans). In the latter case, the initial effect of a dextran induced wilt is a
      leaf wilt presumably caused by the plugging of xylem elements. However,
      physiological experiments including dye transport studies, plasmolytic studies,
      measurements on electrolytes, studies on the movement of (3)H(2)O through tomato
      cuttings, and toxin binding studies all strongly suggest that the primary effect
      of the toxin is to destroy the integrity of cellular membranes resulting in the
      net loss of water from the cell. Membrane damage in toxin treated plants was
      confirmed by electron microscopic observations. Evidence of damage were seen in
      chloroplasts, mitochondria, the plasma membrane, and the structural integrity of
      the cell wall. These effects appeared to be a direct cause and not a secondary
      result of the toxin as shown by autoradiographic studies using (3)H-toxin.

PMID- 16656955
TI  - The effects of ultraviolet irradiation on a coccoid blue-green alga: survival,
      photosynthesis, and photoreactivation.
AB  - The effects of UV irradiation (254 mmu) on a coccoid blue-green alga Agmenellum
      quadruplicatum, Strain PR-6, have been examined in terms of the survival curve
      and measurement of short time photosynthetic rates. From study of survival
      evidence has been found for a strong photoreactivation centered near 430 mmu.
      Measurements of photosynthetic rate suggest that there is a correlation between
      decay of photosynthesis and survival after UV exposure. The UV induced decay in
      photosynthetic activity is reversed by the identical photoreactivation conditions
      that increase the survival level. The photosynthetic data are interpreted as
      demonstrating a photoreactivation of photosynthesis in blue-green algae.

PMID- 16656956
TI  - The association of carbohydrate changes in the shoot tip of cauliflower with
      flowering.
AB  - Changes in levels of sugars and starch in the shoot tip of cauliflower, Brassica
      oleracea L. var. botrytis D. C. cv. Main Crop were studied during periods of
      growth which were inductive or non-inductive to flowering. Flowering was induced
      by growing plants for 2 weeks under 16 hr of light at 5 degrees . During this
      period of floral induction there was a significant increase in sugar and starch
      content compared to that in vegetative plants grown at 20 to 26 degrees . Sugar
      and starch content did not increase and flowering was prevented when light and
      CO(2) were excluded during growth at 5 degrees . A 3-day dark period at 20
      degrees or a high temperature treatment at 33 degrees with light following growth
      at 5 degrees reduced the carbohydrate level and prevented flowering.

PMID- 16656957
TI  - Stimulation of indoleacetic Acid oxidase and inhibition of catalase in cotton
      extracts by plant acids.
AB  - Activity of indoleacetic acid oxidase in partially purified extracts from cotton
      is stimulated by small amounts of malate, succinate, fumarate, and other plant
      acids. The stimulation is apparently due to inhibition of catalase, which is
      detectable in certain preparations. The lag phase of indoleacetic acid oxidation
      by crude preparations is eliminated by steps in processing which conceivably
      either denatures or dilutes catalase, or concentrates inhibitors to catalase.

PMID- 16656958
TI  - Biosynthesis of Insoluble Glucans From Uridine-Diphosphate-d-Glucose With Enzyme
      Preparations From Phaseolus aureus and Lupinus albus.
AB  - Particulate, and digitonin-solubilized, enzyme systems from Phaseolus aureus and
      Lupinus albus catalyze the biosynthesis of aqueous-insoluble glucans from UDP-d
      glucose. The digitonin treatment greatly increases the enzymic activity of (per
      unit protein) both the 34,000g pellet and the supernatant liquid as compared with
      that of the original particles. Most of the polymer produced (90-95%) is soluble
      in hot, dilute alkali; the interglucosidic linkages of the alkali-soluble and
      alkali-insoluble polymers are identical. The optimum concentration for the
      incorporation of radioactivity from UDP-d-glucose-(14)C into soluble glucan is
      high; at 10(-3)m at least 50% of the added radioactive glucosyl donor is
      incorporated.Careful examination of the products of degradation of the polymers
      produced by various enzymic preparations showed that beta-(1-->3)-glucans are
      produced. No evidence was obtained for any measurable amount of beta-(1-->4)-d
      glucose linkages.

PMID- 16656959
TI  - Inositol Metabolism in Plants. VI. Conversion of Myo-Inositol to Phytic Acid in
      Wolffiella floridana.
AB  - When Wolffiella floridana, an aquatic angiosperm in the family, Lemnaceae, was
      grown in axenic culture under continuous light in E medium containing 1.0%
      sucrose and a micromolar amount of (14)C-labeled myo-inositol (MI), MI was taken
      up by the growing plants and converted to phytic acid. After 13 weeks in labeled
      medium during which time there was a 1000-fold increase in fresh weight, 30% of
      the (14)C was recovered in ethanol insoluble residue. Extraction of this residue
      with EDTA released 70% of the label into solution. Phytic acid, identified by
      paper electrophoresis, ion exchange chromatography, and hydrolysis with phytase,
      accounted for most of this radioactivity although some label was also found in
      pentaphosphate and lower phosphate esters of MI. Very little MI was converted to
      cell wall polysaccharides under the conditions used. Results of this study
      indicate that Wolffiella floridana is a convenient tissue for the study of phytic
      acid biosynthesis under laboratory conditions.Lemna gibba G3, grown under short
      day conditions in medium of the same composition as that used for W. floridana,
      also formed labeled phytic acid as well as other labeled lower phosphate esters
      of MI.

PMID- 16656960
TI  - Interactions between potassium and calcium in their absorption by intact barley
      plants. I. Effects of potassium on calcium absorption.
AB  - Increasing concentrations of K (20, 200, 2000 mum) in the nutrient solution
      depressed Ca content and concentration in barley plants growing in nutrient
      solutions of low Ca concentrations (250 and 2500 mum). Increasing K from 20 to
      200 mum depressed Ca absorption more than increasing K from 200 to 2000 mum K.The
      strong depression of Ca absorption by low concentrations of K must involve a
      different process from that studied by other workers at high concentrations of K.
      Since the depression in net absorption of Ca was as great at 250 as at 2500 mum
      Ca the results fail to support previous suggestions that a specific mechanism for
      Ca absorption operates at low Ca concentrations. It is suggested that, at the low
      concentrations of K and Ca likely to be found at the root surface in many soil
      solutions, the above mentioned effect of K in inhibiting Ca absorption may be
      important in the Ca nutrition of plants.

PMID- 16656961
TI  - Interaction Between Potassium and Calcium in Their Absorption by Intact Barley
      Plants. II. Effects of Calcium and Potassium Concentration on Potassium
      Absorption.
AB  - Rates of K absorption by young barley plants grown for 20 days in flowing
      nutrient solutions have been studied at 3 solution K concentrations (20, 200, and
      2000 mum) and at 2 Ca concentrations (250 and 2500 mum). Increasing solution K
      increased plant K content, concentration, and rate of absorption: solution Ca
      concentrations had no effect at any K level.Rates of K absorption were only one
      half to one-fifth of those reported for excised barley roots at similar K
      concentrations in solution. If the reported rates of K absorption by the high
      affinity mechanism in excised barley roots were maintained in growing plants they
      would have given, within 3 days, the equilibrium concentrations of K in plants of
      the present experiment. Thereafter the rates of K absorption by the high-affinity
      mechanism would have been more than adequate to maintain plant K and would need
      to have been compensated by K efflux.It is suggested that, for all concentrations
      of K in solution, the high-affinity mechanism dominates the absorption of K by
      barley plants grown for more than a few days.

PMID- 16656962
TI  - A Hexokinase-initiated Inhibition of Oxygen Uptake in Tomato Fruit Mitochondria
      Uncoupled by Dinitrophenol.

PMID- 16656963
TI  - Invasion of plant tissue by bacteria under in vitro conditions.

PMID- 16656964
TI  - Increased DNA template and RNA polymerase associated with the breaking of seed
      dormancy.

PMID- 16656965
TI  - Formation, Chromophore Composition, and Labeling Specificity of Cyanidium
      caldarium Phycocyanin.

PMID- 16656966
TI  - Determination of root exudates in a steril continuous flow culture. I. The
      culture method.
AB  - A sterile plant culture consisting of culture vessels, culture solution
      container, collecting flasks for percolating nutrient solution, illumination and
      aeration systems and a suitable pump is described. Its difference with other
      culture methods is a very slow, continuous percolation of the nutrient solution
      through the rooting medium. Well defined and controllable conditions can thus be
      established in the rhizosphere over long culture periods. Samples can be
      collected at short intervals without disturbing the rhizosphere in any way nor
      endangering the sterility of the culture. One of the fundamental factors
      determining the special ecological characteristics of the plant rhizosphere is
      the liberation of organic and inorganic substances by the plant root. During the
      study of this phenomenon it became evident that the amount of substances
      liberated varies within wide limits (factors 100 to 1000) according to the
      conditions in which the root is developing.

PMID- 16656967
TI  - Determination of Root Exudates in a Steril Continuous Flow Culture. II. Short
      Term and Long-Term Variations of Exudation Intensity.
AB  - The exudate production of alfalfa under the conditions of the sterile flow
      culture was quantitatively measured. In the first 40 days 3.10(-3) mumoles amino
      N, 2.5 muequivalents of organic acids and approximately 10(-4) mumoles of
      reducing sugars were liberated per plant and per day into the percolating
      nutrient solution. The amino acid concentration in the outflow varies according
      to a daily periodicity. The exudation of a colored substance also shows daily
      periodical variations. This pattern is different from the pattern of the amino
      acid exudation, however, and directly coupled to shoot illumination. Short-term
      2,4-dinitrophenol additions to the nutrient lower the liberation of amino acids
      into the percolating solution.

PMID- 16656968
TI  - Gibberellic Acid-Promoted Lignification and Phenylalanine Ammonia-lyase Activity
      in a Dwarf Pea (Pisum sativum).
AB  - The effects of gibberellic acid on lignification in seedlings of a dwarf and a
      tall cultivar of pea (Pisum sativum) grown under red or white light or in the
      darkness, were studied. Gibberellic acid (10(-6)-10(-4)m) promoted stem
      elongation in both light and dark and increased the percentage of lignin in the
      stems of the light-grown dwarf pea. The gibberellin had no effect on the lignin
      content of the tall pea although high concentrations (10(-4)m) promoted growth of
      the tall plants. Time course studies indicated that the enhanced lignification in
      the gibberellin-treated dwarf plants occurred only after a lag period of several
      days. It was concluded that gibberellic acid-enhanced ligmification had no direct
      relation to gibberellic acid-promoted growth. The activity of phenylalanine
      ammonia-lyase (E.C. 4.3.1.5) was higher in gibberellin-treated dwarf plants grown
      under white or red light than in untreated dwarf plants. Gibberellic acid had no
      detectable effect on the activity of this enzyme when the plants were grown in
      darkness, just as it had no effect on lignification under dark conditions. The
      data suggest that in gibberellin-deficient peas the activity of phenylalanine
      ammonia-lyase is one of the limiting factors in lignification.

PMID- 16656969
TI  - Structural physiological, and biochemical gradients in tobacco pith tissue.
AB  - Explants of tobacco pith taken at various distances from the apex of a mature
      stem show a sharp gradient in growth potential in vitro; growth is highest in the
      extreme apical and basal explants, and is minimal in explants removed ca. 75 cm
      from the apex. Calluses produced by the vigorously growing basal explants are
      harder and more compact than those produced from more apical explants. The
      gradient in growth potential is directly correlated with gradients in RNA,
      protein of cell sap and soluble N per unit fresh weight, but is inversely
      correlated with peroxidase activity. Cell size increases from apex to base of
      plants.The peroxidase activity of pith explants is electrophoretically resolvable
      into 2 isoperoxidases, moving anodically at pH 9.0. During in vitro culture, this
      activity rises, due to the formation of several new isozymes moving toward the
      cathode. The appearance of these isozymes occurs most rapidly in apical and
      extreme basal explants.

PMID- 16656970
TI  - Developmental Physiology of Bean Leaf Plastids II. Negative Contrast Electron
      Microscopy of Tubular Membranes in Prolamellar Bodies.
AB  - Proplastids and prolamellar bodies with tubular membranes were isolated from the
      dark grown primary leaves of bean seedlings (Phaseolus vulgaris L.). The
      combination of fluorescence microscopy and negative contrast electron microscopy
      provided the tentative identification of protochlorophyll holochrome as a
      constituent of prolamellar body membranes and new evidence for solution-filled
      channels within the tubular membrane systems of prolamellar bodies.

PMID- 16656971
TI  - Developmental Physiology of Bean Leaf Plastids III. Tube Transformation and
      Protochlorophyll (ide) Photoconversion by a Flash Irradiation.
AB  - A light flash of about 1 millisecond duration elicits tube transformation in
      paracrystalline prolamellar bodies as well as maximal protochlorophyll(ide)
      photoconversion in etiolated bean leaves (Phaseolus vulgaris L.). These findings
      support a more detailed hypothesis on the linkage between tube transformation and
      protochlorophyll(ide) photoconversion than has been offered previously.

PMID- 16656972
TI  - Second positive phototropism in the Avena coleoptile.
AB  - A method has been developed whereby the second positive phototropism can be
      observed separately from the first positive and negative phototropic responses
      which also occur in oat coleoptiles. Although the second positive phototropic
      response has often been referred to as the base response, photoreception for it
      is shown to occur mainly in the apical 3 mm of the coleoptile. The Bunsen-Roscoe
      reciprocity law, so typical of first positive phototropism, does not apply to the
      second positive responses, and the amount of curvature increases linearly with
      the duration of the stimulus. However, although this linear proportionality
      between stimulus duration and response is the major factor determining response
      at all intensities tested, the intensity of the stimulus does influence the
      response somewhat. The action spectrum for the response shows no activity above
      510 nm and has peaks at 375 and 450 nm. In all but one particular it closely
      resembles the action spectrum for the first positive phototropism, and it is
      concluded that the same, or similar, pigments may well be the photoreceptors for
      both types of response. The identity of this blue light absorbing pigment is not
      known.

PMID- 16656973
TI  - The metabolism of C-labeled isatin and anthranilate in pisum stem sections.
AB  - Isatin, previously shown to promote growth in green and etiolated pea stems, is
      converted mainly to anthranilate in those tissues; small quantities of isatate
      are also formed. Fed anthranilate is converted mainly to its beta-d-glucoside;
      smaller amounts are metabolized to anthranilamide, tryptophan and kynurenine.
      These data provide some basis for understanding the growth promoting activity of
      isatin.

PMID- 16656974
TI  - Differences in Photoresponse and Phytochrome Spectrophotometry Between Etiolated
      and De-etiolated Pea Stem Tissue.
AB  - Morphologically similar pea plants having a 4-fold difference in spectrophoto
      metrically detectable phytochrome can be produced by pretreatment of etiolated
      plants with red light (R) or with red and far-red light combined (RF). A search
      for response differences which could be ascribed to differences in phytochrome
      content has resulted only in the establishment of differences due to de
      etiolation. Segments of etiolated plants differ from those of plants de-etiolated
      by R and RF pretreatments in 2 ways. Segments from etiolated plants appear to
      respond rapidly to the far-red absorbing form of phytochrome (P(FR)), while
      segments from de-etiolated plants do not respond rapidly to P(FR). This statement
      is based upon 2 observations: (i) the red light induced growth inhibition in
      segments from etiolated plants rapidly escapes reversibility by far-red light,
      while with segments from R or RF pretreated plants, the red light effect is fully
      reversed by subsequent far-red light for up to 2 hr; and (ii) segments from
      etiolated plants were inhibited to a greater degree than were segments from RF
      pretreated plants when various photostationary state levels of P(FR) were
      maintained for 30 or 90 min and then removed by photoconversion to P(R). The in
      vivo nonphotochemical transformation curves of the phytochrome of etiolated and
      RF pretreated plants appear to differ in 2 related respects: (i) the amount of
      phytochrome destroyed in de-etiolated tissue is greater than that in etiolated
      tissue, perhaps as a result of the fact that (ii) the rate and extent of apparent
      reversion of P(FR) to P(R) in etiolated tissue is about twice that in de
      etiolated tissue.

PMID- 16656975
TI  - Biogenesis of oxalate in plant tissues.
AB  - Red beet root discs aerated in potassium phosphate for 2 to 3 days and young
      spinach leaves actively produce oxalate. A series of labeled compounds was
      supplied to each of these tissues to determine the extent of conversion to
      oxalate. Similar results were obtained with the 2 tissues except that in the leaf
      tissue glyoxylate and glycolate were outstandingly good precursors. Carbon from
      glucose, acetate, and particularly from some acids of the tricarboxylic acid
      cycle was recovered in oxalate. Extracts from both tissues were found to contain
      an enzyme which converts oxaloacetate to oxalate and acetate. The enzyme was
      partially purified and some of its properties are described. A pathway of oxalate
      synthesis which does not include glycolate or its oxidase is therefore proposed.

PMID- 16656976
TI  - Investigation on photorespiration with a sensitive C-assay.
AB  - A leaf disk assay for photorespiration has been developed based on the rate of
      release of recently fixed (14)CO(2) in light in a rapid stream of CO(2)-free air
      at 30 degrees to 35 degrees . In tobacco leaves (Havana Seed) photorespiration
      with this assay is 3 to 5 times greater than the (14)CO(2) output in the dark. In
      maize, photorespiration is only 2% of that in tobacco.The importance of open leaf
      stomata, rapid flow rates of CO(2)-free air, elevated temperatures, and oxygen in
      the atmosphere in order to obtain release into the air of a larger portion of the
      (14)CO(2) evolved within the tissue in the light was established in tobacco.
      Photorespiration, but not dark respiration, was inhibited by alpha-hydroxy-2
      pyridinemethanesulfonic acid, an inhibitor of glycolate oxidase, and by 3-(4
      chlorophenyl)-1,1-dimethylurea (CMU), an inhibitor of photosynthetic electron
      transport, under conditions which did not affect the stomata. These experiments
      show that the substrates of photorespiration and dark respiration differ and also
      provide additional support for the role of glycolate as a major substrate of
      photorespiration. It was also shown that at 35 degrees the quantity of (14)CO(2)
      released in the assay may represent only 33% of the gross (14)CO(2) evolved in
      the light, the remainder being recycled within the tissue.It was concluded that
      maize does not evolve appreciable quantities of CO(2) in the light and that this
      largely accounts for the greater efficiency of net photosynthesis exhibited by
      maize. Hence low rates of photorespiration may be expected to be correlated with
      a high rate of CO(2) uptake at the normal concentrations of CO(2) found in air
      and at higher light intensities.

PMID- 16656977
TI  - Variation in photorespiration. The effect of genetic differences in
      photorespiration on net photosynthesis in tobacco.
AB  - The hypothesis that net photosynthesis is diminished in many plant species
      because of a high rate of CO(2) evolution in the light has been tested further.
      High rates of CO(2) output in CO(2)-free air in comparison with dark respiration
      were found in Chlamydomonas reinhardi, wheat leaves, tomato leaves, and to a
      lesser extent in Chlorella pyrenoidosa by means of the (14)C-photorespiration
      assay. In tobacco leaves high photorespiration was characteristic of a standard
      variety, Havana Seed, and a possibly still higher rate was found in a yellow
      heterozygous mutant, JWB Mutant. However, the dark homozygous sibling of the
      latter, JWB Wild, had a low photorespiration for the tobacco species. The
      relative rates of photorespiration were in the same sequence when measured by the
      (14)CO(2) released in normal air from leaf disks supplied with glycolate-1-(14)C
      in the light.As would be predicted by the hypothesis, the maximal net rate of
      photosynthesis at 300 ppm of CO(2) in the air in JWB Wild leaves was greater
      (24%) than in Havana Seed, while JWB Mutant had less CO(2) uptake than the
      standard variety (21%). At 550 ppm of CO(2) the differences in net photosynthesis
      were not as great between the 2 siblings as at 200 ppm. The relative leaf
      expansion rates of seedlings of the 3 tobacco varieties in a greenhouse had the
      same relationship as their rates of CO(2) assimilation.Thus within the tobacco
      species, as in a comparison between tobacco and maize, low photorespiratory CO(2)
      evolution was correlated with higher photosynthetic efficiency. Therefore it
      seems that increased CO(2) uptake should be achieved by genetic interference with
      the process of photorespiration.

PMID- 16656978
TI  - Translocation of sugar and tritiated water in squash plants.
AB  - When (14)C-sugar and THO were simultaneously introduced through a cut side vein
      or flap of a squash leaf (Cucurbita melopepo, Bailey cv. torticollis) concurrent
      translocation of (14)C-sugars, T-photosynthates and THO with parallel, almost
      flat, gradients was observed in the petiole for periods of 1 to 3 hr. Parallel
      translocation gradients were not observed when (14)C was introduced as (14)CO(2)
      and T by painting a leaf with THO. Autoradiography of frozen sections to locate
      the tissues in which THO was moving was unsuccessful. Steam-girdling blocked the
      movement of (14)C and T when (14)C-glucose and THO were introduced simultaneously
      by the flap-feeding technique. If THO moved as liquid water in the phloem along
      with the (14)C-sugars, as blockage by steam girdling suggests, then solution flow
      of sugar cannot be excluded as a mechanism of translocation.

PMID- 16656979
TI  - Control of senescence in rumex leaf discs by gibberellic Acid.
AB  - The kinetics of chlorophyll and protein decomposition and the effect of
      gibberellic acid (GA) were examined in senescing leaf discs of Rumex crispus and
      R. obtusifolius. Loss of Rumex total chlorophyll proceeds at a slow rate for
      about 2 days followed by a period of rapid logarithmic decline. Chlorophyll b is
      lost at a slightly faster rate than chlorophyll a during senescence in discs as
      well as in situ. GA causes a complete cessation of net chlorophyll and protein
      degradation for several days in Rumex, in contrast to the incomplete senescence
      inhibition generally observed with cytokinins. GA is fully effective even when
      added at the middle of the logarithmic phase of chlorophyll loss. Senescence
      inhibition by GA is apparently gradually reversed upon GA removal. The
      cytokinins, kinetin and 6-benzylaminopurine, were also effective in Rumex leaf
      discs, indicating that the senescence retarding effect was not restricted to the
      gibberellins.

PMID- 16656980
TI  - Dormancy, Turion Formation, and Germination by Different Clones of Spirodela
      polyrrhiza.
AB  - Some clones of Spirodela polyrrhiza form dormant bodies called turions which
      require several weeks of chilling treatment before they proceed to renew growth
      and develop into vegetative fronds. The individual fronds of Spirodela are less
      than 5 mm long and can be grown aseptically in liquid culture. Turion formation
      and germination can serve as a bioassay for the various compounds involved in
      dormancy development.Turion formation can be induced by manipulation of light
      intensity during the day, photoperiod, night temperature, day temperature, and
      concentration of nitrate in the culture medium. Different clones of Spirodela
      from northeastern United States, Puerto Rico, and Argentina had different
      requirements for turion formation. The clones from Argentina and Puerto Rico did
      not form turions under any of the experimental conditions imposed. Turions of
      some clones required chilling treatments for renewed vegetative growth while
      others did not. Both gibberellic acid and long photoperiods were required to
      bypass the chilling requirements of some clones, but not others.

PMID- 16656981
TI  - Sap tension in flooded trees and bushes of the Amazon.
AB  - The water relations of the inundated forest of the Rio Negro in the Amazon have
      been investigated. The sap pressure in trees and bushes standing in several
      meters of water was found to average between -15 and -20 atm in sunshine. and
      above -10 in overcast. In rainy weather and at night. the pressure would remain
      close to ambient. Submerged leaves had ambient or sometimes very slightly
      positive pressure. Pinnate leaves of legumes folded when the pressure rose above
      a critical level characteristic of the species. Dehydration curves from full
      turgor to negative turgor showed 3 characteristic phases: A) a steep decline in
      pressure when the turgor disappeared; B) a linear decline at zero turgor
      proportional to the increase in osmotic pressure; and C) a steep decline as
      negative turgor (intracellular packing) developed. The tensions in the drowned
      forests were similar to those found in inundated plants of temperate lakes. and
      hence like many plants in a humid forest. However, in the daytime many flooded
      plants of the Amazon reached zero turgor without any external sign of wilting.

PMID- 16656982
TI  - Ribosome particles in corn mitochondria.

PMID- 16656983
TI  - Isolation of Plant Cuticles With Zinc Chloride-hydrochloric Acid Solution.

PMID- 16656984
TI  - An inducible protein in potato and tomato leaflets.

PMID- 16656985
TI  - The Circadian Rhythm of Leaf Movement of Coleus blumei x C. frederici, a Short
      Day Plant. I. Under Constant Light Conditions.
AB  - A new instrument for the recording of leaf movement rhythm is described. Coleus
      blumei x C. frederici, a short day plant, exhibits a circadian rhythm of leaf
      movement. The period length of the free running rhythm is shortest in continuous
      darkness and is increased with an increase in the light intensity. The amplitude
      of the rhythm tends to damp in continuous bright light.

PMID- 16656986
TI  - The Circadian Rhythm of Leaf Movement of Coleus blumei x C. frederici, a Short
      Day Plant. II. The Effects of Light and Temperature Signals.
AB  - The phase response curve for the circadian rhythm of leaf movement of Coleus
      blumei x C. frederici, a short day plant, is generally similar to those reported
      for other organisms. An increase in the duration of the light signal caused an
      increase in the extreme values of the phase response curve and shortened the time
      for transition from maximum delays to maximum advances. Experiments with 2 light
      signals showed that the overt rhythm of leaf movement represents the rhythm of
      the light sensitive oscillator even during the transient period that followed the
      first light signal. A temperature decrease of 7 degrees for 8 hr caused only a
      transient phase shift in the following 2 cycles but not in the steady state. The
      combination of such a temperature decrease and a light signal showed that only
      the overt rhythm of leaf movement was disturbed by the temperature decrease
      whereas the light sensitive oscillator was free running. A temperature decrease
      of 11 degrees for 10 hr caused a steady state phase shift and affected the light
      sensitive oscillator as well.

PMID- 16656987
TI  - The flowering response of coleus in relation to photoperiod and the circadian
      rhythm of leaf movement.
AB  - The flowering response of Coleus frederici and Coleus blumei x C. frederici is
      dependent on the photoperiod; both plants have a critical day length of about 12
      hr. The inductive phase, defined as the period when light signals inhibit floral
      development, started 10 hr after the onset of darkness under 4 and 8-hr
      photoperiods, and 8 hr after the onset of darkness under a 12-hr photoperiod.
      However, a fixed temporal relationship between the inductive phase and the
      minimum leaf position was observed for Coleus frederici. The inductive phase
      always started 5 hr after the minimum leaf position. This evidence supports the
      theory that a circadian clock participates in the time measurement process of
      photoperiodic floral induction.

PMID- 16656988
TI  - Enzymic mechanism of starch breakdown in germinating rice seeds I. An analytical
      study.
AB  - Time-sequence analyses of carbohydrate breakdown in germinating rice seeds shows
      that a rapid breakdown of starch reserve in endosperm starts after about 4 days
      of germination. Although the major soluble carbohydrate in the dry seed is
      sucrose, a marked increase in the production of glucose and maltooligosaccharides
      accompanies the breakdown of starch. Maltotriose was found to constitute the
      greatest portion of the oligosaccharides throughout the germination stage. alpha
      Amylase activities were found to parallel the pattern of starch breakdown. Assays
      for phosphorylase activity showed that this enzyme may account for much smaller
      amounts of starch breakdown per grain, as compared to the amounts hydrolyzed by
      alpha-amylase. There was a transient decline in the content of sucrose in the
      initial 4 days of seed germination, followed by the gradual increase in later
      germination stages. During the entire germination stage, sucrose synthetase
      activity was not detected in the endosperm, although appreciable enzyme activity
      was present in the growing shoot tissues as well as in the frozen rice seeds
      harvested at the mid-milky stage. We propose the predominant formation of glucose
      from starch reserves in the endosperm by the action of alpha-amylase and
      accompanying hydrolytic enzyme(s) and that this sugar is eventually mobilized to
      the growing tissues, shoots or roots.

PMID- 16656989
TI  - Purification and Some Properties of the Nitrogenase From Soybean (Glycine max
      Merr.) Nodules.
AB  - The nitrogenase system in cell-free extracts of soybean nodule bacteroids was
      fractionated into 2 components by use of protamine sulfate or polypropylene
      glycol precipitation followed by chromatography on DEAE-cellulose. Iron and
      molybdenum were concentrated in 1 fraction and iron in the other. Combination of
      fractions resulted in a striking stimulation in activity relative to the activity
      of individual fractions. The effect of different proportions of the 2 fractions
      on specific activities was studied. The ratios of the rates of reduction of
      acetylene and N(2) by extracts or fractions of different purities were relatively
      constant. Extracts or fractions retained most of their nitrogenase activities
      when stored in liquid N(2).

PMID- 16656990
TI  - CO(2) Metabolism in Corn Roots. III. Inhibition of P-enolpyruvate Carboxylase by
      l-malate.
AB  - Phosphoenolpyruvate carboxylase was purified from corn root tips about 80-fold by
      centrifugation, ammonium sulfate fractionation, and anion exchange and gel
      filtration chromatography. The resulting preparation was essentially free from
      malate dehydrogenase, isocitrate dehydrogenase, malate enzyme, NADH oxidase, and
      pyruvate kinase activity. Kinetic analysis indicated that l-malate was a
      noncompetitive inhibitor of P-enolpyruvate carboxylase with respect to P
      enolpyruvate (K(I) = 0.8 mm). d-Malate, aspartate, and glutamate inhibited to a
      lesser extent; succinate, fumarate, and pyruvate did not inhibit. Oxaloacetate
      was also a noncompetitive inhibitor of P-enolpyruvate carboxylase with an
      apparent K(I) of 0.4 mm. A comparison of oxaloacetate and l-malate inhibition
      suggested that the mechanisms of inhibition were different. These data indicated
      that l-malate may regulate CO(2) fixation in corn root tips by a feedback or end
      product type of inhibition.

PMID- 16656991
TI  - Atrazine metabolism in resistant corn and sorghum.
AB  - The metabolism of 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (atrazine) in
      the resistant species, corn (Zea mays L.) and sorghum (Sorghum vulgare Pers.) was
      not the same. In corn, atrazine was metabolized via both the 2-hydroxylation and
      N-dealkylation pathways while sorghum metabolized atrazine via the N-dealkylation
      pathway. Atrazine metabolism in corn yielded the metabolites, 2-hydroxy-4
      ethylamino-6-isopropylamino-s-triazine (hydroxyatrazine), 2-hydroxy-4-amino-6
      isopropylamino-s-triazine (hydroxycompound I), and 2-hydroxy-4-amino-6-ethylamino
      s-triazine (hydroxycompound II). None of these hydroxylated derivatives appeared
      as metabolites of atrazine in sorghum.Hydroxycompounds I and II were formed in 2
      ways in corn: (1) by benzoxazinone-catalyzed hydrolysis of 2-chloro-4-amino-6
      isopropylamino-s-triazine (compound I) and 2-chloro-4-amino-6-ethylamino-s
      triazine (compound II) that were formed by N-dealkylation of atrazine and (2) by
      N-dealkylation of hydroxyatrazine, the major atrazine metabolite in corn. The
      interaction of the 2-hydroxylation and N-dealkylation pathways in corn results in
      the formation of the 3 hydroxylated non-phytotoxic derivatives of atrazine.

PMID- 16656992
TI  - Diurnal pattern of water potential in woody plants.
AB  - The dynamic relationship between the rates of water loss and uptake controls
      plant water status. Marked diurnal variations in water potential of both leaves
      and fruit occurred in all plants studied. Variations in water status during the
      day were most clearly related to changes in evaporative demand of the air and
      were different for the east and west sides of a tree. At night, the plant water
      potential reflected the soil moisture status.Changes in the water potential of
      pear fruit were correlated with changes in fruit diameter. Since water loss from
      fruit occurred mostly through the pedicel into the xylem of the tree, the fruit
      could be used as a crude gauge of xylem water potential, which also showed
      dramatic changes during the day.

PMID- 16656993
TI  - Comparative Studies on Plastoquinones. IV. Plastoquinones in Algae.
AB  - Plastoquinones A and C have been found in all classes of algae, including
      representatives of greens, yellow-greens, blue-greens, reds, browns and the
      flagellate, Euglena. Plastoquinone C from red and brown algae can be separated
      into 6 different types. An additional plastoquinone C has been found in Gigartina
      and Rhydomela. From chromatographic evidence this may be equivalent to
      plastoquinone C(o), a C type with a hydroxyl group on the first isoprene unit of
      the terpenoid sidechain of this substituted benzo-quinone. The ubiquinone,
      vitamin K and alpha-tocopherylquinone content of several algae is also reported.
      The presence of plastoquinone A in all green plants and many algae indicates that
      it may be a functional element in photosynthesis. Our study shows that
      plastoquinone C is more regularly present in algae than has been previously
      shown.

PMID- 16656994
TI  - Effects of Potassium Nutrition on Ribonucleic Acid and Ribonuclease in Zea mays
      L.
AB  - Potassium deficiency decreased the total RNA per shoot in corn (Zea mays L.)
      seedlings due to the reduced sizes of the plant, but increased the ratio of RNA
      to dry matter as much as 40%. Total base composition of RNA was unaffected by
      K(+) deficiency. Thus K(+) deficiency does not appear to alter RNA metabolism to
      such an extent that a lack of RNA becomes a factor limiting growth. The RNA
      contents of leaves were followed as deficiency developed or as the plant
      recovered from deficiency. Such time-course studies, although extremely useful in
      microbial work, did not yield as much information with higher plants. The ratio
      of RNA to dry matter in younger leaves was much higher than that in older leaves.
      The ribonuclease level in corn shoots was increased as much as threefold by K(+)
      deficiency.

PMID- 16656995
TI  - Stomatal Opening in Isolated Epidermal Strips of Vicia faba. I. Response to Light
      and to CO(2)-free Air.
AB  - This paper reports a consistent and large opening response to light + CO(2)-free
      air in living stomata of isolated epidermal strips of Vicia faba. The response
      was compared to that of non-isolated stomata in leaf discs floating on water;
      stomatal apertures, guard cell solute potentials and starch contents were similar
      in the 2 situations. To obtain such stomatal behavior, it was necessary to float
      epidermal strips on dilute KCl solutions. This suggests that solute uptake is
      necessary for stomatal opening.The demonstration of normal stomatal behavior in
      isolated epidermal strips provides a very useful system in which to investigate
      the mechanism of stomatal opening. It was possible to show independent responses
      in stomatal aperture to light and to CO(2)-free air.

PMID- 16656996
TI  - Stomatal Opening in Isolated Epidermal Strips of Vicia faba. II. Responses to KCl
      Concentration and the Role of Potassium Absorption.
AB  - The stimulation by KCl of stomatal opening in isolated epidermal strips of Vicia
      faba was examined. In dark + normal air the opening response was maximal at 100
      mm KCl while in light + CO(2)-free air it was maximal at about 10 mm KCl. CO(2)
      free air was more influential than light in reducing the KCl concentration
      required for maximal opening. K(+) was essential while Cl(-) seemed to be of
      secondary importance in these processes.The use of (86)Rb(+) as a tracer for K(+)
      showed that the increase in stomatal aperture under various conditions was well
      correlated with K(+) uptake. The estimated amount of K(+) taken up by guard
      cells, along with a counter ion, was sufficient to account for the changes in
      solute potential associated with opening. It is suggested that the absorption of
      extracellular solutes, such as K(+), may be the primary mechanism of stomatal
      opening. Both opening and K(+) absorption are stimulated by light + CO(2)-free
      air.The increase in stomatal aperture was also well correlated with the decrease
      in stainable starch in guard cells under all conditions. It is suggested that
      this is a secondary change, although perhaps closely linked to K(+) absorption.

PMID- 16656997
TI  - Studies on a maize mutant sensitive to low temperature I. Influence of
      temperature and light on the production of chloroplast pigments.
AB  - A mutant inbred line of Zea mays L. (M11) in which chlorophyll accumulation is
      particularly sensitive to low temperature is described. Under natural light
      conditions the chlorophyll content of seedlings is negligible below 17 degrees
      but is normal at high temperature. Seedlings of M11 can synthesize chloroplast
      pigments at 16 degrees but at a rate slower than normal. When photo-oxidation is
      minimized, chlorophyll accumulates, and seedlings can photosynthesize efficiently
      at low temperature. The primary site of low temperature sensitivity in M11 is the
      shoot apex where new leaves are developing and undergoing rapid cell expansion.
      It seems that there is impaired development and associated impaired function of
      chloroplasts in M11 grown at low temperatures which sensitizes them to rapid
      photo-oxidation in the light.

PMID- 16656998
TI  - The auxin induced curvature of citrus petals.
AB  - The curvature of citrus petals was studied, using petals implanted in an agar
      sucrose medium. Applications of indoleacetic acid and p-chlorophenoxyisobutyric
      acid and determinations of endogenous auxins indicate that the bending of citrus
      petals is an auxin-mediated process.

PMID- 16656999
TI  - The induction of biplanar growth in fern gametophytes in the presence of RNA base
      analogues.
AB  - The RNA base analogues, 5-fluorouracil, 2-thiouracil, and 8-azaguanine, inhibit
      the growth of Dryopteris borreri, but do not prevent the transition from
      filamentous to biplanar growth. Transition, which occurs only when the filament
      has developed to 4 or 5 cells, may be considerably delayed, due to inhibition of
      filamentous growth, but it always occurs when the critical cell number of the
      filament is reached. Furthermore, the inhibitors show only a marginal
      differential effect on biplanar compared to filamentous growth when the growth
      rates are determined from kinetic studies. It is suggested that the selective
      effects previously reported may result from the experimental techniques used,
      coupled with the actual growth characteristics of the gametophyte.

PMID- 16657000
TI  - Photosynthetic Enhancement in the Diatom Phaeodactylum tricornutum.
AB  - Enhancement phenomena in photosynthesis of the diatom Phaeodactylum tricornutum
      Lewin were studied by means of a Haxo oxygen electrode and 2 monochromatic light
      beams. It was necessary to correct for a minor non-linearity in rate oxygen
      evolution vs. intensity similar to that reported for Chlorella. Action spectra on
      complementary backgrounds and derived enhancement spectra were compared to in
      vivo absorption spectra in identifying the character of pigment systems 1 and 2.
      Fucoxanthin, chlorophyll c, and chlorophyll a-670 are clearly assignable to
      pigment system 2 which absorbs in excess at wavelengths 400 to 678 mmu.
      Chlorophyll a-1 (and a portion of the fucoxanthin) are assignable to pigment
      system 1 which absorbs in excess at wavelengths 678 to 750 mmu. Enhancement
      values were generally lower than those observed in Chlorella or Anacystis and
      lead to conclusion that diatom pigmentation provides an effective light
      harvesting apparatus.

PMID- 16657001
TI  - Oxidative and phosphorylative activities of mitochondria isolated from cotton
      hypocotyls.
AB  - Mitochondria isolated from 2 strains of cotton plant hypocotyls (Gossypium
      hirsutum L. var. Rex smooth leaf and Rex glandless) were examined for their
      oxidative phosphorylation activities. Bovine serum albumin at a relatively high
      concentration was essential in the extraction medium for the isolation of
      oxidatively active mitochondria from both strains of cotton. Phosphorylation was
      obtained only with Rex glandless cotton mitochondria. This activity was low in
      comparison to the mitochondria isolated from soybeans (Glycine max L. var. Lee).
      The endogenous gossypol content was found to be much higher in the Rex smooth
      leaf tissue than in the Rex glandless tissue. In turn, comparable gossypol
      differences were found associated with their respective mitochondrial fractions.
      Exogenous gossypol uncoupled succinate oxidation with active mitochondria
      isolated from soybeans. Gossypol as a possible uncoupler is discussed and
      compared to carbonyl cyanide, m-chlorophenyl hydrazone and 2,4-dinitrophenol.

PMID- 16657002
TI  - Studies on ultrastructure and purification of isolated plant mitochondria.
AB  - Sweetpotato mitochondria, that showed respiratory control, were studied with
      respect to ultrastructure. If fixed in media containing sucrose at 0.4 M, the
      cristae were dilated and the matrix was highly condensed. A more orthodox
      ultrastructural form was observed when the mitochondria were fixed in a medium
      containing sucrose at 0.25 M, i.e., the matrix was more expanded, the cristae
      were less dilated, and peripherally, the inner membrane element lay adjacent to
      the outer membrane element. These results are discussed in terms of a sucrose
      accessible space (space between outer and inner membrane elements including
      intracristal space), and a space relatively inaccessible to sucrose (matrix).
      Ultrastructural shifts were not observed with change in metabolic steady state of
      the mitochondria. High resolution electron micrographs showed that the
      ultrastructure of sweetpotato mitochondria is very similar to that of animal
      mitochondria.Purity and homogeneity of mitochondrial fractions were followed both
      by phase-contrast and electron microscopy. Preparations from sweetpotato, using
      older methods, were relatively homogeneous with respect to particle type and
      size, whereas avocado preparations contained a high proportion of chloroplasts
      and cellular debris. A method of purification involving sucrose-density-gradient
      centrifugation was developed. Purified mitochondria exhibited respiratory control
      and appeared similar to unpurified mitochondria under the electron microscope.

PMID- 16657003
TI  - Opposing Actions of Light in Seed Germination of Poa pratensis and Amaranthus
      arenicola.
AB  - Action spectra were measured for suppression of germination of Poa pratensis L.
      and Amaranthus arenicola I. M. Johnston seed under prolonged or continuous
      irradiation. The action maxima for both types of seeds are near 720 nm. The
      maxima are unchanged in position or magnitude in the presence of radiation in the
      region of 600 to 670 nm adequate to maintain phytochrome predominantly in the far
      red-absorbing form. A reversible potentiation of germination to change in form of
      phytochrome was observed for both seeds. The bearing of these findings on a high
      energy regulatory light response is discussed.

PMID- 16657004
TI  - Effects of Kinetin, IAA, and Gibberellin on Ethylene Production, and Their
      Interactions in Growth of Seedlings.
AB  - Kinetin in concentrations of 10(-8) to 10(-4)m, stimulated ethylene production in
      3 and 4-day old etiolated seedlings of Alaska pea (Pisum sativum L. var. Alaska).
      Seedlings of other species responded similarly. The response to kinetin depended
      on the age of the seedlings.Kinetin alone did not influence ethylene production
      in 6-day old stem sections, but it greatly increased the enhancing effect of
      IAA.Gibberellic acid had no effect on ethylene production by pea seedlings during
      the first 6 days of growth. Ethylene and gibberellic acid are antagonistic in
      their effects on growth of the seedlings; ethylene interfered severely with the
      action of gibberellic acid but did not completely suppress it.The inhibitors
      cycloheximide, cupferron, and N-ethylmaleimide, caused considerable inhibition of
      kinetin-induced ethylene production but were much less effective in the
      endogenous ethylene-forming system.

PMID- 16657005
TI  - ATP Sulfurylase Activity in the Soybean [Glycine max (L.) Merr.].
AB  - ATP sulfurylase activity was assayed in soybean leaf extracts. A simple, rapid
      assay system using molybdate as an analogue of sulfate was developed. The assay
      was coupled to inorganic pyrophosphatase. The high pyrophosphatase level in
      soybean leaf extracts obviated the necessity of adding this enzyme to the assay
      system. ATP sulfurylase has a pH maximum above 7.5, uses molybdate and ATP as
      substrates, and requires magnesium ions for activity.

PMID- 16657006
TI  - Transport of the auxin, picloram, through petioles of bean and coleus and stem
      sections of pea.
AB  - The transport of the synthetic auxin, picloram (4-amino-3,5,6-trichloropicolinic
      acid) was investigated in sections of petioles of Phaseolus vulgaris L. and
      Coleus blumei Benth. and stems of Pisum sativum L. Transport of (14)C-picloram
      was basipolar in all tissues, although the degree of polarity was dependant on
      age. The velocity of picloram movement was calculated at between 0.75 and 1.11
      mm/hr. The amount moved in a given time, the flux, was dependant on the
      concentration applied and the length of the sections used. Picloram did not
      appear to be metabolized by the tissues during the transport experiments. When
      compared to the movement of other growth regulators, picloram transport bears
      marked similarities to that of 2,4-dichlorophenoxyacetic acid.

PMID- 16657007
TI  - Gibberellin-like Substances From Vegetative Tissue of a Conifer, Arizona Cypress.
AB  - Vegetative shoots of Arizona cypress (Cupressus arizonica Greene) were found to
      contain an estimated 40 to 70 mug of gibberellin-like activity per kg. Based on
      elution patterns of silicic acid and celite partition columns, mobilities on thin
      layer chromatograms and specificity of the cucumber, d-3 dwarf maize, dwarf pea,
      and barley half seed bioassays it was possible to determine that the tissue
      contained at least 5 acidic, ethyl acetate-soluble gibberellin-like substances.
      The major one would appear to be GA(3). In addition, GA(9), GA(4), and/or GA(7)
      like compounds, and 2 unidentified gibberellin-like substances are present.

PMID- 16657008
TI  - Uptake of rb and k by excised maize roots.

PMID- 16657009
TI  - Freeze-preservation of cultured flax cells utilizing dimethyl sulfoxide.

PMID- 16657010
TI  - Structure of microbodies in abscission cells.

PMID- 16657011
TI  - Effects of storage and aging on properties of phosphofructokinase from jerusalem
      artichoke tubers.

PMID- 16657012
TI  - Substances essential for a red, far-red light reversible attachment of mung bean
      root tips to glass.

PMID- 16657013
TI  - Environmental factors in the physiology of abscission.
AB  - This paper reviews the physiological effects of the principal environmental
      factors which can influence the process of leaf abscission. The factors include
      temperature, light, water, gases, mineral elements, soil conditions, and
      parasitic organisms. These factors influence a variety of internal physiological
      conditions and processes which in turn may either accelerate or retard the
      process of abscission. The most important internal factors include A) sugar,
      pectin, cellulose, and other carbohydrates; B) energy-yielding respiration; C)
      enzymic reactions; D) amino acids, purines, and other nitrogenous substances; E)
      levels of plant hormones; and F) the molecular biological pathway. The current
      information is consistent with the hypothesis that the environmental factors act
      in leaf abscission via direct or indirect influences on the synthesis or reaction
      rate of enzymes.

PMID- 16657014
TI  - Hormonal regulation of leaf abscission.
AB  - A review is given of the progress made during the last 6 years in elucidating the
      nature, locus of action, and transport properties of the endogenous hormones that
      control leaf abscission.

PMID- 16657015
TI  - Senescence processes in leaf abscission.
AB  - There is a large body of evidence which correlates the development of some phases
      of senescence with the ability of petioles to experience abscission. We have
      suggested that the change-over from stage 1 to stage 2 in the aging of bean
      petiole explants may be a reflection of initial stages of senescence in the
      pulvinar tissue. The abscission-inhibiting effect of auxin in interpretable as a
      retardation of pulvinar senescence. Senescence of cells in the separation layer
      has not been unequivocally established, and it seems unlikely that separation is
      itself a consequence of cellular senescence in the separation zone. More
      probably, senescence plays a role in the preparatory phases of abscission, that
      is, in the development of a condition of responsiveness to ethylene. In bean
      explants, ethylene responsiveness for abscission is associated with an ethylene
      stimulated production of ethylene in the pulvinar tissues.

PMID- 16657016
TI  - Ethylene, plant senescence and abscission.
AB  - Evidence supporting the hypothesis that ethylene is involved in the control of
      senescence and abscission is reviewed. The data indicate that ethylene causes
      abscission in vivo by inhibiting auxin synthesis and transport or enhancing auxin
      destruction, thus lowering the diffusible auxin level. Studies with isolated
      leaves and explants suggest that the gas also may influence abscission by
      accelerating senescence and through an action on plant cell walls. Freshly
      prepared explants produce ethylene at a rate which must be high enough to
      maximally affect the tissue and this may explain why these explants (stage I)
      cannot respond to applied ethylene.

PMID- 16657017
TI  - Anatomical aspects of abscission.
AB  - Anatomical aspects of abscission are reviewed mainly on the basis of experimental
      studies on Coleus, Gossypium, and Phaseolus. In Phaseolus histological studies of
      explants show that petiolar abscission is correlated with the formation of
      tyloses in the vessels proximal to the zone of separation, and that the
      abscission zone is much less well demarcated than in Coleus or Gossypium.
      Radioautographic studies of Phaseolus petiole explants indicate little initial
      difference in the distribution of nucleolar RNA and in nuclear and cytoplasmic
      protein in cells distal (toward the blade) or proximal (toward the stem) to the
      region of separation. However, in ethylene-treated explants an increase in
      nucleolar RNA and in nuclear and cytoplasmic protein is evident in cortical cells
      immediately proximal to the abscission zone, and binucleate cells commonly occur.
      Abscission occurs by dissolution of newly formed cell walls and disruption of the
      mother cell walls in the zone of recently divided cells. It is suggested that the
      experimental results can be explained on the basis of changes induced in levels
      of ethylene in the petiole, the experimental application of ethylene becoming
      effective in expediting abscission only after the endogenous ethylene level in
      explants has declined.

PMID- 16657018
TI  - Cell wall dissolution and enzyme secretion during leaf abscission.
AB  - Cell wall changes leading to the formation of the separation layer during
      abscission of unifoliate (Phaseolus vulgaris) leaves are reviewed. Based on
      evidence from explants and intact plants, dissolution of pectic substances
      between cells of adjacent tissue regions (petiole and pulvinus) is necessary and
      may be sufficient to form the separation layer. Initially, the abscission zone is
      not structurally weak. The decline in break strength accompanying formation of
      the separation layer correlates with the appearance of pectinase activity.
      Pectinase activity is not detectable in freshly harvested explants but increases
      to about 0.09 mug per abscission zone at the time of 50% separation. At the same
      time, water extractable pectin fractions increase with a corresponding decline in
      the pectin fraction extractable with dilute acid. Separation is aided by internal
      shear forces generated by differential growth and hydrostatic pressure or both.

PMID- 16657019
TI  - Control of abscission in agricultural crops and its physiological basis.
AB  - Some naphthalene and phenoxy compounds prevent preharvest drop of apples, pears,
      and citrus fruits. These studies have been complicated by an unrecognized high
      level of ethylene produced by leaves and fruit on trees sprayed with these growth
      regulators. An apparent contradiction is the effectiveness of both 2,4
      dichlorophenoxyacetic acid and n-dimethylaminosuccinamic acid (a growth retardant
      which retards biosynthesis of auxin) in preventing abscission of apples. Thus, in
      the presence of low auxin concentrations in the tissue, this growth retardant
      prevents fruit abscission even more effectively than 2,4-dichlorophenoxyacetic
      acid at high auxin concentrations in the tissue. This anomaly is clarified on the
      basis that n-dimethylaminosuccinamic acid, in the presence of a known low
      ethylene biosynthesis, delays maturity of the fruit and thus prevents fruit
      abscission. On the other hand, 2,4-dichlorophenoxyacetic acid prevents abscission
      by direct growth hormone action, in spite of the side effects of ethylene
      production which speeds ripening of the fruit. With the promotion of abscission
      of leaves and fruit of agricultural crops, attention is given to the use of
      chemicals which induce ethylene production when applied to the plant, but which
      have no growth promotion effect to retard abscission. We can distinguish 5 kinds
      of such chemicals. One group includes gibberellic and abscisic acids that induce
      treated leaves to produce ethylene and abscise (under certain circumstances).
      However, they do not induce ethylene production by fruit and do not promote fruit
      abscission. A second group includes ascorbic acid, which, when used at relatively
      high levels, induces fruit to produce enough ethylene to promote abscission.
      Ascorbic acid-treated leaves also produce ethylene but not enough to cause much
      defoliation. A third group includes protein-synthesis inhibitors, such as
      cycloheximide. When low concentrations (about 30 mumoles/l) are sprayed on the
      fruit, the rapid effect of the freely moving ethylene (produced by the treated
      fruit) appears to mask temporarily any potential effect of the slowly moving
      inhibitor. A fourth group includes 2-chloroethylphosphonic and cupric
      ethylenediaminetetracetic acids, which induce ethylene production of fruit and
      leaves; production by leaves is substantially greater than by fruit and
      substantial defoliation results. A fifth group includes the cotton defoliation
      chemicals which clearly produce ethylene primarily as a result of chemical injury
      to the leaf blade. Another group of compounds, represented by beta
      hydroxyethylhydrazine, produces ethylene by a chemical reaction with formaldehyde
      and water, and the presence of leaves or fruit is not required. At this time we
      are unaware of how chemicals in groups one to four act to promote ethylene
      evolution in leaves and fruit, but possible biological and chemical paths of
      ethylene production are discussed.

PMID- 16657020
TI  - Role of RNA and protein synthesis in abscission.
AB  - The cell separation aspect of abscission is thought to involve the action of
      specific cell wall degrading enzymes. Enzymes represent synthesis which in turn
      is preceded by the synthesis of specific RNA molecules, and it follows that
      inhibition of either of these processes would also block abscission. Since
      abscission is a localized phenomenon usually involving 2 or 3 cell layers, RNA
      and protein synthesis should also be localized. Manipulations of plant material
      which either accelerate or retard abscission may be due to the regulation of RNA
      and protein synthesis. This paper is a review of literature concerned with these
      and related questions.

PMID- 16657021
TI  - Inhibition of Gibberellic Acid-induced alpha-Amylase Formation by Polyethylene
      Glycol and Mannitol.
AB  - Both polyethylene glycol (PEG) and mannitol inhibit gibberellic acid-induced
      alpha-amylase production in barley aleurone layers. The effect of the osmotic
      solution is on enzyme synthesis rather than alpha-amylase secretion. The
      inhibition of alpha-amylase synthesis does not appear to be mediated via an
      indirect effect on respiration or protein synthesis. Rather it seems that the
      osmotic solutions reduce the extent of proteolysis of the stored aleurone grain
      protein thus making available less substrate for new protein synthesis.

PMID- 16657022
TI  - Evidence for bound phytochrome in oat seedlings.
AB  - Phytochrome is consistently observed in pellets centrifuged from homogenates of
      etiolated, 5-day-old oat seedlings. The majority of pigment associated with the
      pellet cannot be removed by buffer washes, nor can appreciable quantities of
      additional phytochrome be adsorbed onto the sedimented material. Over 70% of
      phytochrome in the pellet is released by 1% Triton X-100.Storage at 0 degrees ,
      irradiation by white light, and Triton treatment all cause much greater loss of
      photoreversibility in pelleted phytochrome than in supernatant phytochrome. We
      conclude that the phytochrome in the 1500 to 40,000g (30 min) pellet is distinct
      from the soluble phytochrome in the supernatant.

PMID- 16657023
TI  - The occurrence of nitrate reductase in apple leaves.
AB  - Nitrate reductase utilizing NADH or reduced flavin mononucleotide (FMNH(2)) as
      electron donor was extracted from the leaves, stems and petioles, and roots of
      apple seedlings. Successful extraction was made possible by the use of insoluble
      polyvinylpyrrolidone (Polyclar AT) which forms insoluble complexes with
      polyphenols and tannins. The level of nitrate reductase per gram fresh weight was
      highest in the leaf tissue although the nitrate content of the roots was much
      higher than that of the leaves. Nitrite reductase activity was detected only in
      leaf extracts and was 4 times higher than nitrate reductase activity. Nitrate was
      found in all parts of young apple trees and trace amounts were also detected in
      mature leaves from mature trees. Nitrate reductase was induced in young leaves of
      apple seedlings and in mature leaves from 3 fruit-bearing varieties. An inhibitor
      of polyphenoloxidase, 2-mercaptobenzothiazole was used in both the inducing
      medium and the extracting medium in concentrations from 10(-3) to 10(-5)m with no
      effect upon nitrate reductase activity.

PMID- 16657024
TI  - Phytochrome in Embryos of Pinus palustris.

PMID- 16657025
TI  - Local metabolic autonomy in phycomyces sporangiophores.
AB  - The degree of dependence of the growing zone of the Phycomyces sporangiophore
      upon other parts of the stalk was tested by inhibiting glycolysis and oxidative
      phosphorylation in the stalk below the growing zone. Initially the growing zone
      is capable of nearly normal growth when the metabolism in the rest of the stalk
      is inhibited in this way. However, the growing zone appears to become depleted of
      something normally supplied from below, because after 3 to 4 hr its growth rate
      slows down and the growth stops much sooner than in normal sporangiophores. The
      rest of the sporangiophore appears to have a similar degree of local autonomy
      because isolated sections from below the growing zone can support protoplasmic
      streaming for 10 to 20 hr.

PMID- 16657026
TI  - Xanthium leaf movements in light and dark.

PMID- 16657027
TI  - A technique for the assay of enzymes in intact plant cells in the presence of
      dimethylsulfoxide.

PMID- 16657028
TI  - Ethylene evolution from 2-chloroethylphosphonic Acid.

PMID- 16657029
TI  - Pectin esterase in relation to leaf abscission in coleus and phaseolus.
AB  - Pectin esterase (PE) activities in abscission zones, other portions of leaves,
      and adjacent stem tissues were compared in attached leaves and abscissing
      petioles (previously debladed) of Coleus blumei Benth. and Phaseolus vulgaris L.,
      cv. Canadian Wonder. Earlier findings of Osborne in bean were confirmed and
      changes in PE activity in coleus were shown to resemble those in bean in some
      respects. In both plants PE was lower in the distal portion of abscission zones
      of abscissing petioles than in that portion of attached leaves but this
      difference was not as large or as consistently clear-cut in coleus as in bean.
      The general level of PE activity was an order of magnitude lower and changes
      associated with abscission were smaller in coleus than in bean. Auxin treatment
      of debladed petioles of coleus prevented abscission and resulted in small
      increases in PE activity in abscission zones and most of the other regions
      sampled. The largest increase was observed in the stem tissue adjacent to the
      attached leaf opposite the debladed, auxin treated one.The activity of coleus PE
      was highest in the pH range from 7.3 to 7.6. The pH of distal tissue from
      abscission zones of abscissing petioles was 5.8. This was 0.7 pH units lower than
      that of proximal tissue from the same zones.PE from both coleus and bean appears
      to be denatured by freezing and/or thawing.

PMID- 16657030
TI  - Radioautographic analysis of the distribution of label from h-indoleacetic Acid
      supplied to isolated coleus internodes.
AB  - Isolated fifth internodes of Coleus blumei Benth. were supplied with (3)H-IAA at
      their apical ends. Microradioautography, using thin sections (0.25-0.5 microns)
      of Epon embedded tissue and liquid emulsion techniques, revealed extremely
      specific localization of the acetone-insoluble derivatives of IAA. Changes in the
      patterns of labeling were followed over periods of 3, 24, and 48 hr at various
      distances from the source of applied auxin. Progressively basipetal labeling of
      the cell walls of the youngest xylem elements was evident with time. At the end
      of 24 hr the label was detected also within the cytoplasm or slime of phloem
      elements. After 24 to 48 hr, labeling of plastids was evident. The results
      suggest a continued incorporation of IAA derivatives into cell wall precursors.

PMID- 16657031
TI  - Multiple freezing points as a test for viability of plant stems in the
      determination of frost hardiness.
AB  - A technique is presented for a simple, rapid, and reliable means of determining
      the viability of plant tissue subjected to freezing temperatures. Freezing curves
      of excised stems of Cornus stolonifera Michx., and several other genera were
      studied. Tissue temperature was recorded during freezing of plant stem sections.
      The heat of crystallization deflected the resultant freezing curves at points
      where tissue froze. Living stem sections of all genera studied revealed 2
      freezing points, while dead tissue exhibited only 1. The influence of variables
      such as moisture content, sample size, thermocouple placement, and cooling rate
      on freezing curves was analyzed. Stem samples wrapped in moisture-proof film with
      a thermocouple inserted into the pith were frozen to a predetermined test
      temperature, thawed, and subjected to a second freezing cycle. The presence or
      absence of 2 freezing points in the second freezing cycle was used as a criterion
      for establishing viability. The results were immediately available and identical
      to results from regrowth tests which took about 20 days.

PMID- 16657032
TI  - Leaf structure and translocation in sugar beet.
AB  - Anatomical and ultrastructural details of a translocating 10-cm leaf of sugar
      beet (Beta vulgaris L. var. Klein Wanzleben) were correlated with translocation
      rate data. The minor veins were found to be 13 times as extensive as the major
      veins and measure 70 cm/cm(2) leaf lamina. Measurements disclosed that a 33-mu
      length of minor vein services 29 mesophyll cells with the result that translocate
      moves an average of 73 mu or 2.2 cell diameters during transport from mesophyll
      cells to a minor vein. High-resolution, freeze-dry autoradiography revealed that
      assimilates accumulate in organelle-rich cells of the minor vein phloem.
      Correlation of phloem volume and loading rate for minor veins yielded an uptake
      rate of 735 mumoles of sucrose per g fresh weight of phloem. The arrangement and
      structural features of minor veins appeared to be consistent with the concept
      that vein loading precedes translocation.

PMID- 16657033
TI  - A Study of the Aminoacyl-sRNA Synthetases of Phaseolus vulgaris in Relation to
      Germination.
AB  - Optimum conditions for the extraction and assay by ATP-pyrophosphate exchange of
      the aminoacyl-sRNA synthetases of the various tissues of french bean (Phaseolus
      vulgaris) seeds and seedlings are described. Extracts of plumules, after passage
      through Sephadex G-25, were assayed for synthetase activity using an amino acid
      mixture as substrate, when a 30 to 100-fold stimulation of exchange above the
      endogenous level was obtained. This marked enhancement of exchange by added amino
      acids is largely attributed to the use of dilute extracts.The total synthetase
      activity of the cotyledons was studied in relation to germination. Synthetase
      activity was highest in the dry cotyledon; activity decreased in proportion to
      the loss of protein during germination, i.e. the specific activity of the
      synthetases remained constant for at least the first 6 days of germination. With
      a few minor exceptions, the specific activity of the individual synthetases
      remained constant during germination.The absolute activity of the synthetases of
      the plumule and radicle increased exponentially during germination. The specific
      activity of the synthetases in both tissues increased approximately 2-fold during
      the first 2 to 3 days of germination, then gradually decreased. However the
      asparaginyl-, valyl-, and histidinyl-sRNA synthetases in the plumule did not
      conform with this general pattern.

PMID- 16657034
TI  - Nitrogen assimilation and protein synthesis in wheat seedlings as affected by
      mineral nutrition. I. Macronutrients.
AB  - Deficiencies of each macronutrient (N, P, K, Ca. Mg, S, and Fe) decreased the
      specific activity of nitrate reductase from Triticum aestivum L. seedlings.
      Nitrate content was decreased by N, P, K, Ca, and Mg deficiencies and unaffected
      by S and Fe deficiencies. Glutamic acid dehydrogenase activity was decreased by
      N, P, and S deficiencies, unchanged by K deficiency, and increased by Ca, Mg, and
      Fe deficiencies. Glutamine synthetase activity closely paralleled nitrate
      reductase activity and was decreased by deficiencies of N, P, K, Ca, Mg, and S.
      Glutamic-oxaloacetic transaminase was not sensitive to macronutrient
      deficiencies. High (14)C-leucine incorporation into tissue sections of N-, P-, K
      , Ca-, and S-deficient seedlings did not appear indicative of protein synthesis
      rates in intact seedlings. Nutritional deficiencies apparently depleted
      endogenous amino acid pools and caused less inhibition of exogenous (14)C-leucine
      incorporation into protein.

PMID- 16657035
TI  - Compartmentation of malate in relation to ion absorption in beet.
AB  - Malate in beet discs treated in different salt solutions was labeled by a 30 min
      pulse of (14)CO(2), and subsequent changes in specific activity were followed for
      several hr. In treatments which resulted in net acid synthesis in response to
      excess cation absorption, malate specific activity fell slowly after removal of
      (14)CO(2). In solutions where no net acid synthesis occurred, and from which
      cation and anion were absorbed equally, malate specific activity fell rapidly
      when (14)CO(2) was removed. The foregoing suggests that the net synthesis of
      organic acids in response to excess cation absorption leads to the removal of
      organic anions from cytoplasmic metabolic pools as counter-ions in salt transport
      to the vacuole.The latter hypothesis was further examined by direct measurement
      of the distribution of labeled malate between cytoplasm and vacuole using the
      wash-exchange method of compartmental analysis, previously described for
      inorganic ions. The method satisfied the criterion of exchange specificity
      necessary for this purpose. Much higher retention of label in the cytoplasm was
      observed in KCl solutions (no net synthesis) than in K(2)SO(4) solutions (net
      synthesis) after 3 hr (14)CO(2) fixation and subsequent wash-exchange. The
      observed distribution is consistent with the rapid removal of organic anions to
      the vacuole during net acid synthesis. The significance of organic acid transport
      in relation to metabolism is discussed.

PMID- 16657036
TI  - Phorbic Acid biosynthesis in the latex vessel system of euphorbia.
AB  - Evidence is presented that phorbic acid is formed in the latex producing cell
      system, rather than in photosynthetic or chlorophyll-free tissues of Euphorbia
      resinifera Berg. When a branch of the plant was kept first in a (14)CO(2)
      atmosphere with 12 hr light-dark periods for 2 days and then left under natural
      conditions in the air outside for at least 2 to 3 days, radioactive phorbic acid
      was found in the latex. Phorbic acid synthesis appeared to be independent of the
      photosynthetic and respiratory activities of the plant.Besides phorbic acid 2
      other major radioactive compounds were recognized in the latex, a glycoside or
      oligosaccharide, and a lipid belonging to the group of triterpenoid compounds
      characteristic of the latex in several species of Euphorbia.

PMID- 16657037
TI  - Substrate induction of nitrate reductase in barley aleurone layers.
AB  - Nitrate induces the formation of nitrate reductase activity in barley (Hordeum
      vulgare L. cv. Himalaya) aleurone layers. Previous work has demonstrated de novo
      synthesis of alpha-amylase by gibberellic acid in the same tissue. The increase
      in nitrate reductase activity is inhibited by cycloheximide and 6-methylpurine,
      but not by actinomycin D. Nitrate does not induce alpha-amylase synthesis, and it
      has no effect on the gibberellic acid-induced synthesis of alpha-amylase. Also,
      there is little or no direct effect of gibberellic acid (during the first 6 hr of
      induction) or of abscisic acid on the nitrate-induced formation of nitrate
      reductase. Gibberellic acid does interfere with nitrate reductase activity during
      long-term experiments (greater than 6 hr). However, the time course of this
      inhibition suggests that the inhibition may be a secondary one. Barley aleurone
      layers therefore provide a convenient tissue for the study of both substrate- and
      hormone-induced enzyme formation.

PMID- 16657038
TI  - Biosynthesis of Fatty acids by a soluble extract from developing soybean
      cotyledons.
AB  - Fractionation of developing soybean cotyledons into cellular components
      demonstrates that most of the activity necessary to incorporate acetate-1-(14)C
      into lipid remains in the supernatant from a 198,000g spin for 1 hr. The system
      studied is dependent upon ATP, CoA, and CO(2). Concentrations of ATP greater than
      4 x 10(-3)m are inhibitory, while 1 x 10(-4)m CoA is needed for optimal activity.
      Avidin inhibition of acetate incorporation into lipid could be reversed by
      biotin. Studies indicated that NADPH is a better source of reducing power than
      NADH. The system studied is inhibited by p-chloromercuribenzoic acid and this
      inhibition can be reversed by an excess of GSH. The system studied shows maximum
      activity in tris buffer at pH 8.6 or in glycine buffer, pH 9.4.The distribution
      of acetate into the various fatty acids is greatly influenced by the temperature
      of incubation. Cooler incubation temperatures favor the distribution of acetate
      into the more unsaturated fatty acids.

PMID- 16657039
TI  - Selective Inhibition by Actinomycin D of the Synthesis in Photosynthetic and Non
      photosynthetic Enzymes During the Greening of Etiolated Bean Leaves.
AB  - The effect of actinomycin D on the synthesis of the photosynthetic apparatus
      during illumination of etiolated leaves of Phaseolus vulgaris was studied. The
      increase of chlorophyll content and of the activities of some photosynthetic
      enzymes (NADPH diaphorase, ferredoxin, NADP(+) glyceraldehyde-3-phosphate
      dehydrogenase) was compared with simultaneous measurements of the level of other
      enzymes not considered associated with photosynthesis (ornithine
      transcarbamylase, glucose-6-phosphate dehydrogenase, NAD(+) glyceraldehyde-3
      phosphate dehydrogenase).The effect of the inhibitor on the synthesis of the
      components of the photosynthetic apparatus is much larger than its effect on the
      synthesis of non-photosynthetic enzymes when the antibiotic is supplied 2 hr
      before illumination. The same selective action is also obtained if actinomycin D
      is added after 20 hr of exposure of the leaves to light.The markedly different
      sensitivity to the inhibitor of the synthesis of photosynthetic enzymes, as
      compared to non-photosynthetic ones, is interpreted as a selective inhibition at
      the level of DNA-directed synthesis of RNA molecules.This RNA may be involved
      either in the regulation of chloroplast differentiation or in the specification
      of some component essential for the formation of the plastidial structure or for
      the activity of plastidial ribosomes.

PMID- 16657040
TI  - Effects of freezing and hardening on the sulfhydryl groups of protein fractions
      from cabbage leaves.
AB  - Disc electrophoresis was used to separate water soluble proteins from hardy, non
      hardy, and frost killed cabbage (Brassica oleracea var. capitata) leaves.
      Amidoschwarz staining failed to reveal any new bands as a result of hardening
      although the relative amounts of proteins in individual bands changed. Sulfhydryl
      groups in the protein bands were stained with 2,2-dihydroxy-6,6-dinaphthyl
      disulfide and labeled with (14)C p-chloromercuribenzoate. Significant decreases
      in the sulfhydryl content of the total water soluble protein were found during
      hardening and as a result of frost death. The decrease during hardening was
      paralleled by a significant increase in the water soluble protein. There was a
      significant increase in the sulfhydryl content per unit high molecular weight
      protein but a decrease in the sulfhydryl content per total protein as a result of
      frost death. This was interpreted as evidence for intermolecular disulfide bond
      formation during freezing.

PMID- 16657041
TI  - Evidence for metabolic turnover of monoterpenes in peppermint.
AB  - Two types of experimental evidence are presented which suggest that the
      monoterpenes of peppermint (Mentha piperita L.) are subject to metabolic
      turnover. In kinetic studies with (14)CO(2), peppermint cuttings rapidly
      incorporate label into the monoterpenes and then lose most of the label from the
      monoterpenes, without corresponding changes in the amount of monoterpenes
      present. When peppermint plants are grown in a controlled environment (16-hr
      photoperiod, 24 degrees day, 8 degrees night) and analyzed at intervals leaf pair
      by leaf pair, there is a steady increase in monoterpenes until the time of floral
      initiation, followed by a rapid decrease. It is suggested that monoterpenes may
      serve as substrates for energy metabolism in the secretory cells after other
      stored substrates have been depleted.

PMID- 16657042
TI  - Effectiveness of certain sterilizing agents for seedling incubation in
      radiothymidine.
AB  - Failure of seed sterilization methods and breakdown in sterile technique can
      result in catabolism of thymidine by microorganisms during seedling incubation in
      radioisotope. The effectiveness of some sterilizing agents was monitored by
      microbiological methods and by thin layer chromatography for the presence of
      thymidine degradation products. Sodium hypochlorite and ethylene oxide each
      sterilized pea and sunflower seeds. Sodium hypochlorite failed to sterilize onion
      seeds while ethylene oxide was only occasionally effective and often retarded
      germination. Captan, commonly used before germination to prevent fungal blight of
      seedlings, did not reduce the bacterial flora of onion seeds.

PMID- 16657043
TI  - Growth regulator induced movement of photosynthetic products into fruits of
      ;black corinth' grapes.
AB  - The effect of exogenous growth regulators on movement of assimilates into flowers
      and young fruits of ;Black Corinth' grapes was studied. Clusters were treated
      with growth regulator and after 0.5 hr to 5 days the leaves above the clusters
      were exposed to (14)CO(2). Control shoots received (14)CO(2) but no growth
      regulator. At harvest, counting and radioautographic techniques were used to
      ascertain amount and distribution of activity in clusters. Clusters were dipped
      in 4-CPA (4-chlorophenoxyacetic acid), GA(3) (gibberellic acid), or BA
      (benzyladenine). All berries were heavier than controls within 3 days. Total
      counts in the fruits were increased by 4-CPA, and the distribution of
      radioactivity among the sugar, organic acid, and amino acid fractions was usually
      altered by all treatments. In a time series experiment, within 6 hr after
      treatment of fruits with GA(3) there was almost an 8-fold increase in total
      counts relative to the control. After 12 hr there was about a 9-fold and 6-fold
      increase in counts in tartaric and malic acids, respectively, and in gamma
      aminobutyric acid, pipecolic acid, and valine increases of 56, 150, and 330%.
      Radioactivity in fructose was increased 70% in gibberellin-treated clusters over
      the controls. After 96 hr there were only about 1000 cmp per g fr wt in controls,
      but there were about 31,000 cpm counts in treated clusters. Treatment of clusters
      with gibberellin attracted less assimilates into the fruits when shoots had also
      been sprayed with gibberellin. Dipping portions of clusters in gibberellin
      increased the movement of (14)C assimilates into the treated portions. Hormonal
      control of mobilization is discussed.

PMID- 16657044
TI  - Ethylene production from propanal.
AB  - Tracer studies using a model system consisting of Cu(2+) and ascorbate indicate
      that carbons 2 and 3 of propanal are converted to ethylene, and carbon 1 is
      converted to formic acid and CO(2). A mechanism accounting for this reaction is
      described. In apple tissue, methionine but not propanal is readily incorporated
      into ethylene. It is therefore concluded that propanal is not a precursor of
      ethylene in this fruit.

PMID- 16657045
TI  - Control of logarithmic growth rates of tobacco callus tissue by cytokinins.
AB  - The growth rates of tobacco callus tissues on media containing 10(-6) to 10 mum 6
      (gamma,gamma-dimethylallylamino)purine (2iP) were measured. At concentrations of
      10(-4) mum and above growth rates were exponential and dependent on cytokinin
      concentration. At 2iP concentrations of 10(-4) to 0.33 mum, the exponential rate
      was maintained for 4 to 5 doublings of fresh and dry weight. After this period a
      linear phase, resulting in approximately 1 doubling of weight, occurred. The
      growth of tissues on media containing higher than 0.33 mum 2iP was exponential
      for only about 15 days. At the end of this time, and well before they achieved
      half their final weight, they exhibited growth which was less rapid than
      logarithmic but more rapid than linear. Comparisons with zeatin, 6
      benzylaminopurine and kinetin indicated that, although the maximum growth rates
      obtained with relatively high concentrations (0.1-1 mum) were similar, the
      naturally occurring cytokinins, 2iP and zeatin, promoted faster rates at lower
      concentrations (10(-3)-10(-2) mum) than did 6-benzylaminopurine and kinetin.

PMID- 16657046
TI  - Studies on polyphenol content, activities and isozymes of polyphenol oxidase and
      peroxidase during air-curing in three tobacco types.
AB  - The change in polyphenol content in the primed leaves of burley, flue-cured, and
      Turkish tobaccos during air-curing was related to the activities and isozymes of
      polyphenol oxidase and peroxidase. The quantity of chlorogenic acid was rapidly
      reduced during the first week of curing. The decrease in rutin content during
      curing was less significant, especially when the concentration of chlorogenic
      acid was high in leaf tissues. This result was further confirmed by in vitro
      assays with partially purified tobacco polyphenol oxidase.The polyphenol oxidase
      activity did not differ at any stage of curing in the 3 tobaccos. When the
      activity was measured by the oxidation of 3,4-dihydroxyphenylalanine it rose
      rapidly during the first day of curing and then decreased sharply so that in the
      fully cured leaf only 15% activity remained. The increase in activity was not
      observed when chlorogenic acid was used as the substrate. A similar level of
      peroxidase activity was found in the 3 tobaccos before curing. Peroxidase
      activities increased rapidly during the first 24 hr of curing, declined
      thereafter, and remained highest in the flue-cured tobacco, less in the Turkish
      line, and least in the burley at the end of curing process.By polyacrylamide gel
      block electrophoresis, 10 peroxidase isozyme bands, 2 cationic and 8 anionic,
      appeared identical in all 3 tobaccos. When catechol replaced benzidine-2 HCl as
      the electron donor, 1 cationic and 2 anionic peroxidase isozymes did not form. Of
      interest is that the same 10 peroxidase isozyme bands also exhibited polyphenol
      oxidase activities when treated with 3,4-dihydroxyphenylalanine or chlorogenic
      acid. Results suggest that in the crude tobacco leaf extract the peroxidase and
      polyphenol oxidase may associate as protein complexes, and peroxidase isozymes
      may differ in electron-donor requirements. Isozyme patterns for both oxidases at
      various curing intervals differed only quantitatively.

PMID- 16657047
TI  - Biological and chemical properties of the epidioxide isomer of abscisic Acid and
      its rearrangement products.
AB  - The growth inhibitory activity of the epidioxide (II), a precursor in the
      synthesis of abscisic acid (ABA), has been confirmed with additional assay
      systems. Under physiological conditions the epidioxide is rearranged to give ABA
      and an isomer of ABA which has probably the structure V. This major product has
      very low, if any, biological activity. The biological activity of the epidioxide
      is explained by its partial conversion (about 20%) to ABA. The reaction rate was
      enhanced by heavy metal ions and decreased by EDTA. At pH 12.5, the decomposition
      of the epidioxide is slower than it is near neutrality and ABA is the predominant
      product. In the biological systems studied the activity of the epidioxide can be
      accounted for by nonenzymatic conversion to ABA.

PMID- 16657048
TI  - Plant Leaf and Stem Proteins. II. Isozymes and Environmental Cabbage.
AB  - The activity of 10 enzymes separated by acrylamide disc gel electrophoresis of
      leaf and stem extracts from Dianthus grown under summer and winter conditions was
      studied. While banding was constant and highly reproducible under each
      environment, differences between the 3 cultivars and between the tissues were
      evident. No significant differences in the isozyme patterns of glutamate
      dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate
      dehydrogenase, malate dehydrogenase, and catalase were observed between the 2
      environments. Loss of activity was observed under winter conditions with amylase
      and lactate dehydrogenase and loss of certain isozymic components was evident
      with acid phosphatase and esterase. Prominent changes were observed in peroxidase
      isozymes, the hardy cultivars developing additional isozymic components under
      winter conditions. Only minor changes in the total protein banding were seen. The
      enzymes showed considerable stability in those tissues killed by the freezing
      conditions.

PMID- 16657049
TI  - Host-Pathogen Interactions: I. A Correlation Between alpha-Galactosidase
      Production and Virulence.
AB  - Resistance or susceptibility of Red Kidney, Pinto and Small White beans
      (Phaseolus vulgaris) to the alpha, beta, and gamma strains of Colletotrichum
      lindemuthianum was either confirmed or established. These fungal strains secrete
      alpha-galactosidase, beta-galactosidase and beta-xylosidase when grown on cell
      walls isolated from the hypocotyls of any of the above bean varieties. These
      enzymes effectively degrade cell walls isolated from susceptible 5-day old
      hypocotyls but degrade only slightly the walls isolated from resistant 18-day old
      hypocotyls. The amounts of the beta-galactosidase and beta-xylosidase secreted by
      the 3 fungal strains are relatively low and are approximately equivalent. The
      secretion of these 2 enzymes is not dependent upon the bean variety from which
      the hypocotyl cell walls used as a carbon source were isolated. However, the
      fungal strains secrete greater amounts of alpha-galactosidase when grown on
      hypocotyl cell walls isolated from susceptible plants than when grown on walls
      from resistant plants. Virulent isolates of the fungus, when grown on hypocotyl
      cell walls isolated from a susceptible plant, secrete more alpha-galactosidase
      than do attenuated (avirulent) isolates of the same fungal strain grown under the
      same conditions. The alpha-galactosidase secreted by each of the fungal strains
      is capable of removing galactose from the hypocotyl cell walls of each bean
      variety tested. Galactose is removed from the cell walls of each variety at the
      same rate regardless of whether the cell walls were isolated from a susceptible
      or resistant plant.

PMID- 16657050
TI  - Gene locus specificity of the glucose effect in the thiamine pathway of the
      angiosperm, Arabidopsis.
AB  - All mutants at 3 loci in Arabidopsis thaliana (L.) Heynh., a higher plant, that
      are associated with the synthesis or coupling of the thiazole moiety of thiamine
      are susceptible to reversible glucose inhibition. In contrast, several different
      alleles involved in the synthesis of the pyrimidine moiety of the vitamin are
      insensitive to glucose. Glucose and maltose are equally effective inhibitors
      while fructose, lactose, ribose, and xylose are toxic. This toxicity is not
      released by added thiamine.

PMID- 16657051
TI  - Specific requirement of potassium for light-activated opening of stomata in
      epidermal strips.
AB  - The effect of various ions on stomatal opening was studied in isolated epidermal
      strips of Vicia faba L. Stomata in strips floating on 10 mm KCl and in CO(2)-free
      air opened in light, closed in subsequent darkness, then opened fully again when
      illuminated. A light-activated highly specific effect of K(-) (and Rb(+)) on
      opening was found. When strips were floated on high concentrations (50 or 100
      meq/liter) of Li(+), Na(+) or Cs(+), stomata opened but light had very little
      effect on the concentrations required for opening. With K(+), the opening
      produced in the dark was the same as with the other alkali ions. Light, however,
      lowered more than 100-fold the concentration of K(+) required for maximal
      opening. Thus only the effect of K(+) (and Rb(+)) was greatly accentuated by
      light. NH(4) (+) and Mg(2+) did not produce opening.No specific anion is required
      in association with K(+). Opening was the same when Cl(-), Br, and NO(3) (-) were
      used as counter ions, but was less when SO(4) (2-) was used, particularly at
      higher concentrations and in the dark.The results are discussed in relation to
      the recent proposal that the basis for stomatal opening is K(+) uptake in amounts
      sufficient to act as an osmotic agent. This work also demonstrates, for the first
      time, a physiological process specifically requiring K(+). Assuming that ion
      uptake is an integral part of stomatal opening, guard cells would appear to have
      an ion uptake mechanism of a degree of specificity previously unknown in higher
      plants.

PMID- 16657052
TI  - Ethylene-induced Isocoumarin Formation in Carrot Root Tissue.
AB  - The concentrations of 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin (MMHD)
      formed in carrot roots inoculated with certain fungi or treated with indole-3
      acetic acid, 2,4-dichlorophenoxyacetic acid, or 2,4,5-trichlorophenoxyacetic acid
      (2,4,5-T), were related to the amount of ethylene produced by the root tissue.
      Ethylene applied exogenously in concentrations above 0.3 ppm induced the
      formation of MMHD in carrot root discs. Continued production of MMHD required the
      continued presence of ethylene. The amounts of MMHD in the discs were reduced by
      CO(2), an inhibitor of ethylene action, and by reduction of the partial pressure
      of ethylene in fungus-inoculated or 2,4,5-T-treated carrot root discs. The
      results indicate that ethylene is required for the induction of MMHD formation by
      carrot root tissue.

PMID- 16657053
TI  - Glycolate and glyoxylate metabolism by isolated peroxisomes or chloroplasts.
AB  - Chloroplasts, mitochondria, and peroxisomes from leaves were separated by
      isopycnic sucrose density gradient centrifugation. The peroxisomes converted
      glycolate-(14)C or glyoxylate-(14)C to glycine, and contained a glutamate:
      glyoxylate aminotransferase as indicated by an investigation of substrate
      specificity. The pH optimum for the aminotransferase was between 7.0 and 7.5, and
      the Km for l-glutamate was 3.6 mm and for glyoxylate, 4.4 mm. The reaction of
      glutamate plus glyoxylate was not reversible. The isolated peroxisomes did not
      convert glycine to glyoxylate nor glycine to serine.Peroxisomes did not oxidize
      glycolate or glyoxylate to CO(2). Chloroplasts could very slowly oxidize
      glyoxylate, but not glycolate, to CO(2). Chloroplast oxidation of glyoxylate was
      heat labile and widely distributed among plants. Oxidation was stimulated by
      light and oxygen. but was not inhibited by 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU).A scheme for the distribution of enzymes associated with
      glycolate metabolism and photorespiration is presented. Glycolate biosynthesis
      occurs in the chloroplasts. In the peroxisomes, glycolate is oxidized with O(2)
      uptake to glyoxylate by glycolate oxidase, and the glyoxylate is converted to
      glycine by glutamate:glyoxylate aminotransferase. Further metabolism of glycine
      does not occur in the peroxisomes. It is possible that excess glyoxylate from the
      peroxisomes could return to the chloroplasts to be reduced to glycolate or
      oxidized to account for part of the CO(2) loss during photorespiration.

PMID- 16657054
TI  - Kinetics of abscission in the bean petiole explant.
AB  - The progress of bean petiole abscission has been followed using quantitative
      measurements of the mechanical force required to break explants at the separation
      zone. It is found that the shortest time for a measurable effect of ethylene (1
      ppm) in stimulating the development of frangibility is about 1 hr. Removal of the
      ethylene is followed by a return to the endogenous rate of weakening, the slower
      rate being established in 1 hr. Application of the inhibitor cycloheximide leads
      to a cessation of abscission development within one-half hr. As in the
      stimulations of certain plant processes with auxins, gibberellins, and
      cytokinins. ethylene stimulation of abscission requires the continuous presence
      of the regulator.

PMID- 16657055
TI  - Absorption of copper, zinc, and manganese by sugarcane leaf tissue.
AB  - The absorption of Cu(2+), Zn(2+), and Mn(2+) by leaf tissue of 4-month old
      sugarcane plants (Saccharum officinarum L., var. H53-263) has been investigated.
      After the "apparent free space" fraction was desorbed, the absorption of Cu(2+),
      Mn(2+), and Zn(2+) yielded a curve typical of many ion uptake processes when
      measured as a function of the external concentration. However, only 1 absorption
      mechanism was evident for each cation. The pH optimum for Cu(2+) and Zn(2+)
      uptake was 5.0 to 6.0, whereas that for Mn(2+) absorption was 4.5 to 6.0.
      Absorption was competitively inhibited by H(+), and this inhibition was
      reversible when 0.5 mm Ca(2+) was present. Cu(2+) and Zn(2+) were absorbed
      through the same carrier sites, as concluded from their mutually competitive
      activities. Mn(2+) was absorbed through a second, independent mechanism. Uptake
      of each cation was strongly inhibited by uncouplers of oxidative phosphorylation,
      by Amytal and Nembutal(2), by 5 x 10(-2)m succinate, and by ADP and P(i).
      Absorption of Cu(2+), Zn(2+), and Mn(2+) was concluded to be coupled to oxidative
      phosphorylation, and specifically to energy-conservation Site I.

PMID- 16657056
TI  - Stimulation of lettuce seed germination by ethylene.
AB  - Ethylene increased the germination of freshly imbibed lettuce (Lactuca sativa L.
      var. Grand Rapids) seeds. Seeds receiving either red or far-red light or darkness
      all showed a positive response to the gas. However, ethylene was apparently
      without effect on dormant seeds, those which failed to germinate after an initial
      red or far-red treatment. Carbon dioxide, which often acts as a competitive
      inhibitor of ethylene, failed to clearly reverse ethylene-enhanced seed
      germination. While light doubled ethylene production from the lettuce seeds, its
      effect was not mediated by the phytochrome system since both red and far-red
      light had a similar effect.

PMID- 16657057
TI  - Avena coleoptile elongation: stimulation by fluorophenylalanine.
AB  - A 100 to 150% stimulation of Avena coleoptile segment elongation by the amino
      acid analogue p-fluorophenylalanine (FPA) has been observed. The effect is
      reversed by phenylalanine and is not seen with comparable concentrations of
      sodium fluoride. FPA does not alter elongation of red-irradiated segments.
      Stimulation by FPA occurs only when the apex is intact and the segments are
      incubated in the absence of exogenous auxin. In the presence of FPA, (14)C
      leucine uptake by coleoptile segments is reduced by 34% and protein synthesis by
      42%. When pre-incubated on labeled media and subsequently transferred to
      unlabeled media, segments fail to incorporate into the protein fraction any of
      the previously absorbed label. It is therefore difficult to ascertain whether FPA
      results in a genuine inhibition of protein synthesis in apical coleoptile
      segments. Possible mechanisms for the action of FPA and its relationship to light
      dependent elongation are considered.

PMID- 16657058
TI  - Respiratory metabolism in mangrove seedlings.
AB  - The respiratory gaseous exchanges of detached whole mangrove seedlings
      (Avicennia, Bruguiera, Rhizophora) in a range of O(2) concentrations from 0 to
      21% (air) were markedly reduced by the presence of external CO(2). Aerobic
      respiration decreased steadily for 16 days but the RQ remained at unity.In anoxia
      CO(2) output fell to half that in air. Ethanol accumulation was negligible but,
      relatively, acetaldehyde values were higher than in other tissues. Lactate
      accumulated initially but later decreased. On return to air CO(2) output was
      elevated above control values in a pattern resembling the previous lactate
      accumulation. The extent of the burst was too great, and the RQ too low, to be
      explained entirely by lactate oxidation.In 5 or 10% O(2) the CO(2) outputs were
      below those in anoxia and the RQ eventually rose to 1.4, suggesting the induction
      of fermentation. The absence of ethanol, acetaldehyde or lactate indicates that
      CO(2) was released from reactions other than those in the Embden-Meyerhof
      pathway.Tissue slice CO(2) outputs decreased with lowered O(2) concentrations and
      the RQ was always above unity except in air. The burst on return to air was
      absent, suggesting that slicing affects decarboxylation mechanisms.

PMID- 16657059
TI  - Enzyme activities of the carbon reduction cycle in some photosynthetic organisms.
AB  - Profile analyses of the enzymes comprising the photosynthetic carbon reduction
      cycle have been performed in extracts of dark grown and greening Euglena gracilis
      var. bacillaris. Chlorella pyrenoidosa grown photoautotrophically, in the light
      with glucose or in the dark with glucose, Tolypothrix tenuis, Chromatium and
      leaves of spinach. Amounts of activity are compared with the level of
      photosynthetic CO(2) fixation. Only in Chromatium were all enzyme activities
      sufficient to support the in vivo rate of CO(2) fixation. In organisms other than
      Chromatium, some enzymes and particularly fructose 1,6-phosphatase and ribulose
      1.5-diphosphate carboxylase appeared to be present in insufficient amounts to
      support the photosynthetic rate of the intact cell. Developmental studies with
      Euglena and growth studies with Chlorella led to the conclusion that these
      enzymes were associated with the cycle. Suppression of CO(2) fixation in
      heterotrophically grown Chlorella was accompanied by a striking decrease in the
      same enzymes whose activities increased in greening Euglena.

PMID- 16657060
TI  - The plasmalemma: seat of the type 2 mechanisms of ion absorption.

PMID- 16657061
TI  - Ethylene and ripening of mangoes.

PMID- 16657062
TI  - Isolation of tightly coupled mitochondria from acidic plant tissues.

PMID- 16657063
TI  - Hormonal Control of Senescence of Bean Endocarp: Auxin-suppression of RNase.

PMID- 16657064
TI  - Oxidation of paraffins by plant tissues.

PMID- 16657065
TI  - Ethylene as a Component of the Emanations From Germinating Peanut Seeds and Its
      Effect on Dormant Virginia-type Seeds.
AB  - The embryonic axes of Spanish-type peanut seeds that do not exhibit dormancy to
      any extent were found to produce ethylene during germination. Virginia-type
      peanut seeds of the extremely dormant variety NC-13 produced low levels of
      ethylene when imbibed but not germinating. Treatments that released dormancy of
      NC-13 peanut seeds resulted in increased ethylene production by the embryonic
      axis. The estimated internal concentration of ethylene in Virginia-type peanut
      seeds was 0.4 ppm at 24 hr of germination. Fumigation with an external
      concentration of 3.0 to 3.5 ppm for 6 hr was sufficient to break dormancy of
      Virginia-type peanut seeds. These results suggest that ethylene is associated
      with the germination processes of non-dormant seeds and participates in the
      breaking of seed dormancy of dormant peanut varieties.

PMID- 16657066
TI  - Stimulation of ethylene evolution and abscission in cotton by 2
      chloroethanephosphonic Acid.
AB  - Ethrel, a mixture of 2-chloroethanephosphonic acid and its ethyl ester, hastens
      abscission of leaves, debladed petioles, and flower buds of cotton plants
      (Gossypium hirsutum, L.). Both young and old leaves abscissed while still green.
      Application of Ethrel stimulated evolution of ethylene, and this response
      preceded abscission. Air concentrations of ethylene around enclosed, treated
      plants were adequate to produce abscission in plants. Non-treated plants
      defoliated when enclosed with plants sprayed with Ethrel. The stimulation of
      abscission of explant petioles by Ethrel was reversed by naphthalene acetic acid.
      The stimulation of abscission by Ethrel was concluded to be mediated by ethylene.

PMID- 16657067
TI  - Prunin identification, biological activity and quantitative change in comparison
      to naringenin in dormant peach buds.
AB  - Prunin (naringenin 7-glucoside), which was identified in dormant peach buds, was
      found to act as a growth inhibitor of wheat coleoptile elongation.Quantitative
      estimation on a fresh weight basis of the flavonoid in peach buds revealed a high
      level in late summer, a steep decrease in autumn that became more moderate during
      the winter, with lowest values near bud swell in spring. Two periods of
      reaccumulation of prunin during October and January fitted 2 periods of arrested
      growth of the resting bud. A negative correlation was demonstrated between prunin
      and naringenin levels during August through October. It is proposed that prunin
      might act as a precursor for naringenin that accumulates in resting buds in
      autumn. It is suggested that the system glucoside-aglucone-beta glucosidase might
      have regulatory properties in the dormant bud.

PMID- 16657068
TI  - Influence of Certain Cations on Activity of Succinyl CoA Synthetase From Tobacco.
AB  - Succinyl CoA synthetase from Nicotiana tabacum exhibited a requirement for
      univalent and divalent cations. Mn(2+) replaced Mg(2+) in the assay medium and
      Co(2+) and Ca(2+) partially replaced Mg(2+). Addition of Zn(2+) resulted in no
      enzyme activity. The enzyme was activated by univalent cations K(+), Rb(+), NH(4)
      (+), and Na(+); Li(+) showed little or no activation. Maximum enzyme activity
      varied significantly with potassium salts of different anions. Greatest
      activation was obtained with K(3)PO(4) and, respectively, KCl, KNO(3), K(2)SO(4)
      and KF exhibited steadily decreasing enzyme activation.

PMID- 16657069
TI  - Photoreaction of manganese catalyst in photosynthetic oxygen evolution.
AB  - The formation of active O(2) evolving centers following addition of Mn(2+) to Mn
      deficient Anacystis nidulans cells yielded an estimate of 6 to 12 Mn atoms
      associated with each O(2) evolving reaction center. Restoration of activity upon
      addition of Mn ions is affected in 3 ways: (1) Stimulation of the uptake of
      exogenous Mn into the cells-this uptake occurs in darkness, but is enhanced 5 to
      10 fold by light; a high concentration of DCMU (1 x 10(-5)m) decreases this light
      enhanced influx no more than 50 to 75%; (2) Photoreactivation of the O(2)
      evolving centers, after excess Mn has been accumulated in the cells essentially
      no increase in Hill activity is observed unless the cells are illuminated. This
      photoreactivation is fully inhibited by 10(-6)m DCMU and partially by
      benzoquinone. The Q(10) of photoreactivation proper is close to 1; (3)
      Photoinhibition of the activation-photoreactivation occurs most effectively in
      weak intensities (< one-fiftieth photosynthetic saturation in normal cells).
      Apparently at higher intensities an inhibitory photoprocess is overriding. This
      inhibition proved reversible. The photoreactivation leads to new stable O(2)
      evolving centers as evidenced by an increase in the rate at saturating intensity,
      quantum yield, and the O(2) gush.

PMID- 16657070
TI  - Metabolism of arginine by aging and 7 day old pumpkin seedlings.
AB  - The metabolism of arginine by etiolated pumpkin (Cucurbita moschata) seedlings
      was studied over various time and age intervals by injecting arginine-U-(14)C
      into the cotyledons. At most, 25% of the (14)C was transported from the cotyledon
      to the axis tissue and the amount of this transport decreased with increasing age
      of the seedlings. The cotyledons of 25 day old plants contained 60% of the
      administered (14)C as unmetabolized arginine. Little (14)C was in sugars and it
      appeared that arginine was the primary translocation product. Time course studies
      showed that arginine was extensively metabolized and the labeling patterns
      suggest that different pathways were in operation in the axis and cotyledons. The
      amount of arginine incorporated into cotyledonary protein show that synthesis and
      turnover were occurring at rapid rate. Only 25% of the label incorporated into
      protein by 1.5 hr remained after 96 hr. The label in protein was stable in the
      axis tissue. By 96 hr 50% of the administered label occurred as (14)CO(2) and it
      appeared that arginine was metabolized, through glutamate, by the citrio acid
      cycle in the cotyledons. The experiments showed that an extensive conversion of
      arginine carbon into other amino acids did not occur.

PMID- 16657071
TI  - Digestive Secretion of Dionaea muscipula (Venus's Flytrap).
AB  - The digestive fluid of Dionaea muscipula has been studied with respect to its
      protein content as a function of time after entrapment of protein material and
      some enzymes of the secretion. Maximum secretion of enzyme occurs within the
      first 3 days of the digestive cycle and protein reaches its maximum at 4 days.
      Phosphatase, proteinase, nuclease and amylase have been observed in the
      secretion. The enzymes have acid pH optima and the proteinase has a molecular
      weight of about 40,000.

PMID- 16657072
TI  - 6-(gamma,gamma-Dimethylallylamino)Purine As A Precursor of Zeatin.
AB  - A 6-(gamma,gamma-dimethylallylamino) purine-like compound was found in the
      culture medium of Rhizopogon roseolus, which had been shown earlier to synthesize
      zeatin. The role of 6-(gamma,gamma-dimethylallylamino) purine as a precursor of
      zeatin was studied. Rhizopogon was furnished with 6-(gamma,gamma
      dimethylallylamino) purine-8-(14)C. Cochromatography, oxidation studies with
      potassium permanganate, and bromination indicated that labeled zeatin
      ribonucleoside was isolated from the medium. The fungus also incorporated labeled
      adenine, hypoxanthine, and 4-amino-5-imidazole carboxamide into zeatin
      ribonucleoside.

PMID- 16657073
TI  - Monovalent ion stimulated adenosine triphosphatase from oat roots.
AB  - Monovalent ion stimulated ATPase activity from oat (Avena sativa) roots has been
      found to be associated with various membrane fractions (cell wall, mitochondrial
      and microsomal) of oat roots. The ATPase requires Mg(2+) (or Mn(+2)) but is
      further stimulated by K(+) and other monovalent ions. The monovalent ions are
      ineffective in the absence of the divalent activating cation. The ATPase has been
      described with respect to monovalent ion specificity, temperature, pH, substrate
      specificity, and Mg(2+) and K(+) concentrations. It was further shown that
      oligomycin inhibits a part of the total ATPase activity and on the basis of the
      oligomycin sensitivity it appears that at least 2 membrane associated ATPases are
      being measured. The mitochondrial fraction is most sensitive to oligomycin and
      the microsomal fraction is least sensitive to oligomycin. The oligomycin
      insensitive ATPase appears to be stimulated more by K(+) than the oligomycin
      sensitive ATPase.It was further shown that per gram fresh weight of roots,
      approximately 0.7 to 0.8 mumoles of K(+) were absorbed per mumole of K(+)
      stimulated ATP hydrolysis. This result was obtained for a variety of K(+)
      concentrations and was taken to mean that sufficient membrane associated ATPase
      exists to account for K(+) transport in the oat roots.

PMID- 16657074
TI  - Level of photosynthetic intermediates in isolated spinach chloroplasts.
AB  - The level of intermediates of the photosynthetic carbon cycle was measured in
      intact spinach chloroplasts in an attempt to determine the cause of the induction
      lag in CO(2) assimilation. In addition, transient changes in the level of the
      intermediates were determined as affected by a light-dark period and by the
      addition of an excess amount of bicarbonate during a period of steady
      photosynthesis. Assayed enzymically were: ribulose 1,5-diphosphate, pentose
      monophosphates (mixture of ribose 5-phosphate, ribulose 5-phosphate and xylulose
      5-phosphate, hexose monophosphates (mixture of glucose 6-phosphate, glucose 1
      phosphate, and fructose 6-phosphate), glyceraldehyde 3-phosphate,
      dihydroxyacetone phosphate, glycerate acid 3-phosphate, a mixture of fructose 1,6
      diphosphate and sedoheptulose 1,7-diphosphate, adenosine triphosphate (ATP),
      adenosine diphosphate (ADP), and adenosine monophosphate (AMP).The lag in CO(2)
      fixation appeared to be the result of low levels of pentose monophosphates. The
      level of ribulose 1,5-diphosphate was roughly equal in chloroplasts showing
      immediate linear kinetics with respect to CO(2) fixation and chloroplasts which
      exhibited an initial lag.Following a light-dark transition, CO(2) fixation ceased
      immediately but the level of glycerate 3-phosphate increased while ribulose 1,5
      diphosphate was only slightly effected. The increase in level of glycerate 3
      phosphate was correlated with a decrease in triose phosphate. Within 3 to 5 min
      in the light, ATP reached a maximum concentration while in darkness, all was
      utilized in 30 to 60 sec. The rapid loss of ATP was ascribed to an ATPase rather
      than to its utilization in kinase reactions.A rapid increase in CO(2)
      concentration enhanced the level of triose phosphate, but the level of glycerate
      3-phosphate showed only a small overshoot and was considered as evidence that
      reducing power was not a rate limiting factor. Data were obtained indicating that
      triose phosphates similar to pentose monophosphates and in contrast to fructose 6
      phosphate, glucose 6-phosphate and glucose 1-phosphate could be transported
      between chloroplast and suspending medium. Differential import and export of
      phosphorylated compounds may serve as routes alternative to starch and sucrose
      for the flow of carbon into biosynthetic pathways.

PMID- 16657075
TI  - Temperature Regulation of Endogenous Gibberellin Activity and Development of
      Tulipa gesneriana L.
AB  - The changes in the contents of free and bound gibberellin-like activity (GA) of
      Tulipa gesneriana L. cv. Ralph during development under 2 temperature conditions
      were studied. The results show that the content of free GA of bulbs grown at 18
      degrees increased by 67% over the initial level during development. The bound GA
      showed a slight initial increase and was followed by a rapid decrease. In
      contrast, bulbs treated at 13 degrees showed a marked decline in free GA and a 2
      fold increase in the content of bound GA. However, after the transfer of these
      bulbs from 13 degrees to 18 degrees the free GA increased to the initial level
      while the bound GA decreased to a low level.The rate of floral shoot and root
      development and time of flowering were accelerated at 18 degrees as compared to
      13 degrees .From the data obtained, it was suggested that a temperature-sensitive
      interconversion mechanism between free and bound GA exists in tulip bulbs and
      that there is apparent synthesis or transformation of these phytohormones during
      development of the bulbs.

PMID- 16657076
TI  - Modification of metabolic pattern by variation of nicotinamide adenine
      dinucleotide phosphate level.
AB  - The experiments were designed to get some information on the metabolism
      controlled by variation of the NADP level, which is known to change with the
      variation of environmental factors.The exogenous NADP added to the mitochondria
      prepared from Vigna sesquipedalis cotyledons was associated with and/or
      penetrated into the mitochondria. The combined NADP served in the operation of
      the mitochondrial NADP-isocitric acid dehydrogenase.The variation of NADP level
      by exogenous NADP was observed to modify the rates of metabolic processes. The
      increase of exogenous NADP in Vigna hypocotyl slices lowered malic- and citric
      acid contents and raised the alpha-ketoglutaric acid content. The incorporation
      of (14)C from acetate-2-(14)C into lipid, organic acid, amino acid, was promoted
      with the exogenous NADP. The (14)C-incorporation into glycolic acid, malic acid
      and glutamic acid was accelerated.In the mannitol homogenate of Vigna cotyledon,
      (14)CO(2) evolution and (14)C-incorporation into lipid, sugar, and glycolic acid
      from acetate-2-(14)C were promoted with the exogenous NADP. Endogenous citric
      acid content was lowered by NADP, while malic acid content was increased.The
      activation of NADP-enzymes by NADP was discussed to be involved in these
      variations.

PMID- 16657077
TI  - The Respiratory Chain of Plant Mitochondria. III. Oxidation Rates of the
      Cytochromes c and b in Mung Bean Mitochondria Reduced With Succinate.
AB  - Oxidation rates of the 2 cytochromes c and the 3 cytochromes b in mitochondria
      from the hypocotyls of etiolated mung beans (Phaseolus aureus) have been measured
      with a rapid mixing flow apparatus coupled to a dual wavelength
      spectrophotometer. The mitochondria were depleted with uncoupler and ADP prior to
      starting the experiments to minimize the complications caused by energy-linked
      processes on electron transport. The half-time for oxidation and absorbance
      change at a given wavelength for the rapidly oxidized cytochromes was plotted as
      a function of wavelength, with 570 mmu as reference, to yield a spectrum in which
      absorbance maxima and half-times were correlated. The 2 cytochrome c components
      have oxidation half-times of 2 milliseconds for c(549) and 3 milliseconds for
      c(547). (The subscripts refer to the difference absorbance maxima observed for
      these cytochromes in reduced-minus-oxidized difference spectra obtained at -196
      degrees . The maxima observed at room temperature are 550 mmu for c(547) and 552
      mmu for c(549).) Cytochrome b(557) (room temperature maximum 560 mmu) was
      oxidized with a half-time of 8 milliseconds, while b(553) (room temperature
      maximum 556 mmu) was oxidized relatively slowly with a half-time of 0.5 sec.
      Cytochrome b(562) (room temperature maximum 565 mmu) was oxidized with half-times
      in the range 15 to 35 milliseconds, depending on mitochondrial preparation. It
      was shown that b(562) is only partially reduced by succinate in anaerobic
      mitochondria previously depleted with uncoupler and ADP; this cytochrome can be
      fully reduced by succinate in coupled mitochondria under conditions where
      endogenous pyridine nucleotide is also reduced. Both b(553) and b(557) in
      depleted mitochondria are reduced in anaerobiosis by succinate. With ascorbate
      plus N,N'-tetramethylphenylenediamine as substrate, b(553) is only partially
      reduced in anaerobiosis, while b(557) is completely reduced in depleted
      mitochondria. This observed difference in ease of reducibility provides another
      method for differentiating the 3 cytochromes b of mitochondria isolated from
      plant tissues.

PMID- 16657078
TI  - Cyclic Photophosphorylation in Vivo and its Relation to Photosynthetic CO(2)
      Fixation.
AB  - Salicylaldoxime (2 x 10(-3)m and less) inhibits cyclic photophosphorylation in
      intact Chlorella cells severely whereas photosynthetic O(2)-evolution and
      (14)CO(2)-fixation is hardly affected. Cyclic photophosphorylation in vivo was
      measured by following anaerobic light dependent glucose uptake. A similar
      difference in susceptibility has been observed with carbonylcyanide-p
      trifluoromethoxyphenylhydrazone. Various controls exclude the possibility that
      the difference in inhibition was caused by differing experimental conditions or,
      in the case of glucose assimilation, by an inhibition of a reaction other than
      photophosphorylation.There also exists a great difference in light saturation of
      cyclic photophosphorylation and photosynthesis. Evidence is reported that at
      light saturation of glucose uptake light driven cyclic phosphorylation is indeed
      the limiting reaction.The results are considered as evidence that cyclic
      photophosphorylation does not contribute ATP stoichiometrically to photosynthetic
      CO(2)-fixation.

PMID- 16657079
TI  - Effects of 3,5-Dihalogenated-4-hydroxybenzonitriles on the Activity of
      Mitochondria From White Potato Tubers.
AB  - Effects of the herbicide 3,5-diiodo-4-hydroxybenzonitrile (ioxynil), and its
      dibromo and dichloro analogs, upon the respiration of mitochondria isolated from
      white potato tubers (Solanum tuberosum L.) were investigated. Mitochondrial
      mediated oxygen uptake was monitored polarographically with a platinum oxygen
      electrode.With succinate as substrate for mitochondrial oxidation, ioxynil
      stimulated both ADP-limited and ADP + phosphate-deficient oxygen utilization.
      Ioxynil also circumvented oligomycin-inhibited respiration and slightly
      stimulated mitochondrial ATPase activity. Responses produced by ioxynil on
      respiration were similar to, but occurred at lower concentrations than, those of
      2,4-dinitrophenol.The dibromo- and dichloro-substituted analogs of ioxynil also
      stimulated ADP-limited respiration and released oligomycin-inhibited oxygen
      uptake. Based on concentration, the decreasing order of uncoupling activity was I
      > Br > Cl with respect to the halogen substituents.

PMID- 16657080
TI  - Inhibition of the Hill Reaction by Tris and Restoration by Electron Donation to
      Photosystem II.
AB  - Experiments in which chloroplasts were washed with tris and tricine buffers at
      different pH's indicated that the non-protonated (uncharged) form of tris was
      inhibitory to the Hill reaction while the protonated form of tris and the
      zwitterionic forms of tricine were non-inhibitory. Buffers analogous to tris and
      tricine gave similar results. Photoreduction of NADP could be restored to the
      inhibited chloroplasts by adding the reduced forms of p-hydroquinone, p
      aminophenol, p-phenylenediamine, benzidine, semicarbazide, and dihydroxydiphenyl,
      all of which donated electrons to photosystem II. Photoreduction of ferricyanide
      was shown with those donor systems (benzidine and semicarbazide) which did not
      react chemically with ferricyanide. Photophosphorylation was also restored with
      all of the electron donors except semicarbazide.

PMID- 16657081
TI  - Sterol biosynthesis in sub-cellular particles of higher plants.
AB  - Mevalonic acid-2-(14)C was administered to cut stems of bean seedlings (Phaseolus
      vulgaris L.) for time intervals varying from 20 min to 24 hr. The plants were
      homogenized in a pH 7.8 tris-sucrose buffer and the homogenates separated into
      chloroplast, mitochondrial, microsomal, and supernatant fractions by means of
      differential centrifugation. The distribution of radioactivity into non
      saponifiable material in each of the fractions was then determined. After short
      incubation periods labeled squalene was localized in the supernatant fraction.
      Labeled sterol was limited at all incubation periods to the microsomal and
      supernatant fractions. The data presented clearly implicate the microsomal and
      supernatant fractions in sterol biosynthesis in higher plants.

PMID- 16657082
TI  - Abscission: role of cellulase.
AB  - Cellulase (beta-1,4-glucan-glucanohydrolase EC 3.2.1.4) activity increased during
      abscission and was localized in the cell separation layer of Phaseolus vulgaris
      L. cv. Red Kidney (bean), Gossypium hirsutum L. cv. Acala 4-42 (Cotton) and
      Coleus blumei Benth. Princeton strain (Coleus) abscission zone explants.
      Cellulase activity was optimum at pH 7, was reduced by one-half after heating to
      55 degrees for 10 min, and was associated with the soluble components of the
      cell. Explants treated with aging retardants (indoleacetic acid, (6)N
      benzyladenine, and coumarin), CO(2), actinomycin D or cycloheximide had less
      cellulase activity than untreated controls. Ethylene increased cellulase activity
      of aged explants after a 3-hr lag period but had no effect on cellulase activity
      of freshly excised explants. It was concluded that 1 of the roles of ethylene in
      abscission is to regulate the production of cellulase which in turn is required
      for cell separation.

PMID- 16657083
TI  - Isoenzymes of glutamate dehydrogenase in plants.
AB  - Glutamate dehydrogenase of several different plants was resolved by
      polyacrylamide gel electrophoresis into separate molecular forms and the
      isoenzymic patterns detected by the tetrazolium technique were compared. The
      number of isoenzymes and their electrophoretic mobilities varied among the
      different plants studied. The isoenzymes were found to have the same coenzyme
      specificity and to localize in the mitochondrial fraction of the cell in all the
      plants examined. Electrophoretic heterogeneity in tissue homogenates was observed
      in some of the plants studied. The pattern of isoenzymes of mungbean hypocotyl
      was followed and shown to change during germination.

PMID- 16657084
TI  - Response of pea stem tissues with different phytochrome contents to red light
      dosage.

PMID- 16657085
TI  - Artifacts in intracellular enzyme distribution caused by alkaline homogenates.

PMID- 16657086
TI  - Actions of gibberellic and abscisic acids on lettuce seed germination without
      actions on nuclear DNA synthesis.

PMID- 16657087
TI  - Immunochemical Studies on Arachis hypogaea Proteins With Particular Reference to
      the Reserve Proteins. I. Characterization, Distribution, and Properties of alpha
      Arachin and alpha-Conarachin.
AB  - Fourteen antigenic constituents have been detected in Arachis hypogaea seeds. The
      major proteins of the classic arachin and conarachin fractions have been
      identified. Arachin contains 4 antigens (the major one called alpha-arachin) and
      conarachin contains 2 which have been called alpha(1), and alpha(2)-conarachin.
      Structural differences between alpha-arachin, alpha(1) and alpha(2)-conarachin
      are indicated by their different antigenic specificities. alpha-Arachin
      precipitates as a separate entity at low temperature. The action of trypsin on
      this protein induces an increase in electrophoretic mobility and prevents
      precipitation at low temperature. This enzyme has no detectable effect on
      alpha(1) and alpha(2)-conarachin.The proteins of the cotyledon and of the entire
      axis are quite similar in their immunoelectrophoretic patterns. However,
      quantitative and qualitative differences occur between the proteins found in the
      cotyledon and those of the 1-millimeter tip of the axis. In the latter, there is
      a 4-fold smaller proportion of alpha-arachin than in the cotyledon.
      Immunoelectrophoretic analysis of subcellular preparations from cotyledons
      confirms that alpha-arachin is an aleurin and that alpha(1)-conarachin is a
      typical cytoplasmic protein. Large and small aleurone grains appear very similar
      in their qualitative antigenic composition.

PMID- 16657088
TI  - Immunochemical Studies on Arachis hypogaea Proteins With Particular Reference to
      the Reserve Proteins. II. Protein Modification During Germination.
AB  - alpha-Conarachin and alpha-arachin are metabolized differently during
      germination. The amount of alpha-conarachin decreases without the appearance of
      antigenic intermediary compounds. alpha-Arachin retains its original antigenic
      structure and becomes more anodic during germination, but a number of
      intermediary proteins, differing widely in electrophoretic mobility, form up to
      14 days germination. The electrophoretic shift of alpha-arachin, detectable after
      1 day of germination, might be caused by progressive deamidation of glutamine and
      asparagine. Decreases in amide content of protein extracted after germination
      support the hypothesis and suggest that alpha-arachin provides the first source
      of ammonia to the new seedling.New antigenic proteins are synthesized in both
      roots and cotyledons during germination. Some appear organ specific, whereas
      others are identical in both the cotyledons and the roots. Appearance and
      disappearance of each new protein is unique with respect to period of germination
      and hence might correspond to specific events of germination.

PMID- 16657089
TI  - Carrier-mediated Potassium Efflux Across the Cell Membrane of Red Beet.
AB  - The flux ratio (influx/efflux) of K(+) across the plasmalemma of beet cells at an
      external potassium concentration of 0.6 mm does not respond to changes of
      membrane potential in the manner expected for the free diffusion of ions. The
      K(+) efflux is affected by the presence of adsorbed Ca(2+), but is apparently
      unrelated to the electrical potential or to the net uptake of potassium. The K(+)
      efflux is greater than the efflux of the sulfate and organic anions which are
      accumulated with potassium, and is partially dependent on the presence of
      external potassium. Thus the loss of (42)K from the cell does not appear to be a
      leakage of freely diffusing K(+) ions, nor a leakage of ion pairs, but a carrier
      mediated transport or exchange of potassium across the cell membrane.

PMID- 16657090
TI  - Phototropism and photoinhibition of basipolar transport of auxin in oat
      coleoptiles.
AB  - We have proposed that the lateral inequality of auxin associated with the
      phototropic response is a consequence of a light-induced impairment of basipolar
      transport of the hormone. If this is so, the dose-response curve for
      photoinhibition of auxin transport should resemble that for phototropism.
      Further, the wavelength dependencies of the transport and tropic response should
      also be similar. Oat coleopilles were irradiated equilaterally with white light
      and with broad- and narrow-spectral bands of blue light. Indoleacetic acid 2
      (14)C was then applied apically to the intact coleoptile. Irradiation by the 3
      sources inhibited basipolar transport of the auxin. The photoinhibition of
      transport increases with exposure, reaches a maximum at radiant energies
      depending on the source used, and then decreases. The dose response for transport
      inhibition matches that for phototropism. A correspondence in the spectral
      response of the 2 phenomena is also found for coleoptiles exposed to first
      positive energies at various wavelengths from 340 to 730 nm. We interpret these
      correlations as support for the hypothesis that phototropism is mediated by a
      photoinhibition of basipolar transport of auxin.

PMID- 16657091
TI  - Phosphorus compounds in translocating Phloem.
AB  - Phosphate-(32)P was introduced into a turnip leaf, and 3 hr later, the vascular
      bundles were stripped from the petiole and their phosphate ester pattern was
      studied. The pattern did not alter along their length and was like that of other
      tissues. Pumpkin leaves were painted with phosphate-(32)P; and later, the
      petioles were cut, the sieve tube exudates were collected and their phosphate
      ester patterns were studied. Exudates collected after 10 min had a high
      proportion of their (32)P present in P(i) and nucleoside triphosphates, while
      exudates collected after long translocation times (4-22 hr) had a lower
      proportion in these, and a higher proportion in hexose monophosphates and UDP
      glucose. In general, the ester patterns were like those of other tissues. The
      results indicate that sieve tubes are metabolically active, and that P(i) is the
      primary form in which phosphorus moves in the phloem.

PMID- 16657092
TI  - Gibberellin and CCC Effects on Flowering and Growth in the Long-day Plant Lemna
      gibba G3.
AB  - The application of gibberellic acid (GA(3)) to the non-rosette long-day plant
      Lemna gibba G3 at concentrations from 0.1 to 100 mg/l did not induce flowering on
      short days and inhibited flowering on long days at concentrations of 1 mg/l and
      higher. On both short and long days GA(3) concentrations above 1 mg/l caused a
      decrease in frond size and fresh and dry weight, but an increase in the rate of
      frond production and thus an increase in the # VF (number of vegetative fronds).
      Identical results were obtained when gibberellin A(7) was used instead of
      GA(3).The addition of the plant growth retardant CCC [(2-chloroethyl)
      trimethylammonium chloride] to the culture medium on long days resulted in almost
      complete inhibition of flowering at 10(-3) M. Vegetative growth was also
      inhibited to some extent. With CCC at 10(-3) M the simultaneous addition of GA(3)
      resulted in partial reversal of flower inhibition with 0.3 mg/l GA(3) being
      optimal. The inhibition of vegetative growth as measured by fresh and dry weight
      was also partially reversed by GA(3), but the threshold concentration for
      reversal of flower inhibition was at least 10 times lower than that for
      inhibition of vegetative growth.These results are interpreted as indicating that
      gibberellins are important for flowering in the non-rosette long-day plant L.
      gibba G3, but apparently are present in non-limiting concentrations on short
      days.

PMID- 16657093
TI  - Fat Metabolism in Higher Plants. XXXVII. Characterization of the beta-Oxidation
      Systems From Maturing and Germinating Castor Bean Seeds.
AB  - In the maturing castor bean seed (Ricinus communis), maximum beta-oxidation
      appears at 28 days after flowering and in the germinating seed, 4 days after
      germination. Highest specific activities for both beta-oxidation systems and
      their component enzymes are associated with cytosomal particles banding at a
      density of 1.25 g/ml in a sucrose gradient. Substrate specificity studies
      indicate that of several fatty acids, ricinoleate is oxidized most rapidly by the
      preparation from the maturing seed (28 days after flowering) while palmitate and
      linoleate are oxidized most rapidly by extracts obtained from tissue germinated
      for 4 days. The beta-oxidation activities observed in both systems reflect the
      expression of activity of at least 3 of the component enzymes, crotonase, beta
      hydroxyacyl dehydrogenase and beta-keto-thiolase, which rise and fall co
      ordinately. Acyl thiokinase does not appear to play a limiting role in regulating
      beta-oxidation per se under the conditions employed here.

PMID- 16657094
TI  - Penetration of iron and some organic substances through isolated cuticular
      membranes.
AB  - Cuticular membranes were isolated enzymically from tomato fruits and from the
      dorsal and ventral surfaces of the leaves of Euonymus japonicus. Penetration of
      Fe from FeSO(4) and FeEDDHA (ferric ethylenediamine di(o-hydroxyphenylacetate) in
      the absence and presence of urea through the isolated cuticular membranes was
      studied. Fe from FeSO(4) penetrated more rapidly through the cuticles than Fe
      from FeEDDHA. Urea reduced the penetration of Fe from FeSO(4) and FeEDDHA.
      Binding of Fe on the inner surfaces of tomato fruit cuticles was also reduced by
      EDDHA.The results on the rates of penetration of (14)C-labeled organic substances
      suggest a possible relationship with their molecular weights. Permeability
      coefficients for these solutes have been derived for the 3 types of cuticles,
      using Fick's equation. The penetration rates of all substances through stomatous
      cuticles far exceeded those through astomatous cutioles.

PMID- 16657095
TI  - Metabolism of the alpha-Pyridone Ring of Ricinine in Ricinus communis L.
AB  - Chemically synthesized ricinine-3,5-(14)C was used to study the metabolism of
      this alkaloid in the plant which produces it, Ricinus communis L. In a time
      course study, ricinine-3,5-(14)C was administered to a series of castor plants
      (Ricinus communis L.) and the radioactivity recovered in the ricinine samples
      showed a decrease with increase in time. It was also observed that the alkaloid
      was translocated to the seed. The in vivo conversion of ricinine-3,5-(14)C to
      respiratory (14)CO(2) occurred in both light and dark and indicated that the
      alpha-pyridone ring of ricinine could be degraded.In a comparison of the ricinine
      content of the various tissues it was observed that in the yellow leaf only a
      trace amount of the alkaloid was present. Preliminary results indicated that the
      yellow leaf can also metabolize ricinine-3,5-(14)C to (14)CO(2).

PMID- 16657096
TI  - Energy and Electron Transfer Systems of Chlamydomonas reinhardi. I.
      Photosynthetic and Respiratory Cytochrome Systems of the Pale Green Mutant.
AB  - The role of cytochromes in photosynthetic electron transfer system has been
      studied using the pale green mutant of Chlamydomonas reinhardi (ATCC 18302). The
      existence of cytochromes b(563) and f is confirmed, while no significant amount
      of ascorbate-reducible cytochrome b(559) is detected in this mutant. The presence
      of cytochrome c and a small amount of a-type cytochrome is determined in these
      cells.Light-induced oxidation of cytochrome b(563) is eliminated by oxygen
      induced oxidation, and oxygen-induced oxidation is greatly diminished under
      illumination. Antimycin A diminishes the oxygen-induced oxidation of cytochrome
      b(563), but does not affect light-induced oxidation. In the aerobic state in the
      presence of 2-heptyl-4-hydroxyquinoline-N-oxide, cytochrome b(563) is reduced by
      illumination with far red light; this reduction is not inhibited by 3-(4'
      chlorophenyl)-1,1-dimethylurea.A tentative scheme for the electron transfer
      system in chloroplasts, which involves a cyclic pathway via cytochrome b(563) and
      its interaction with oxygen, is proposed.

PMID- 16657097
TI  - Photosynthetic Light Reactions in Chemically Fixed Anacystis nidulans, Chlorella
      pyrenoidosa, and Porphyridium cruentum.
AB  - The photochemical activities of various species of unicellular algae (Anacystis
      nidulans, Chlorella pyrenoidosa, and Porphyridium cruentum) were studied
      following chemical fixation. Fixation with formaldehyde and glutaraldehyde
      yielded cells which retained their ability to perform photosystem I and
      photosystem II reactions. The photochemical efficiencies of some fixed algae are
      as great as those of unfixed spinach chloroplasts. Fixed algae containing
      accessory pigments appear to be useful models for further studies of the light
      reactions of photosynthesis.

PMID- 16657098
TI  - Action Spectra for Photosystems I and II in Formaldehyde Fixed Algae.
AB  - Action spectra were obtained for photosystems I and II in chemically fixed algal
      cells and for photosystem I in unfixed lysozyme treated cells. Untreated algal
      cells yielded neither of the 2 light reactions with the reaction mixtures used.
      The action spectra for photosystem I in the blue-green alga Anacystis nidulans
      and red alga Porphyridium cruentum follow the absorption spectrum of chlorophyll
      a with a small peak in the region of the accessory pigments. In the green alga
      Chlorella pyrenoidosa the photosystem I action spectrum follows the absorption
      spectrum of chlorophyll a. Photosystem II action spectra in A. nidulans and P.
      cruentum follow the absorption spectra of the accessory pigments while that in C.
      pyrenoidosa is shifted slightly toward the blue spectral region. These results
      provide additional evidence that formaldehyde fixed cells are valid models for
      studying the light reactions of photosynthesis.

PMID- 16657099
TI  - Photosynthetic light reactions in chemically fixed spinach thylakoids.
AB  - After proper fixation with glutaraldehyde, spinach thylakoids retain both
      photosystem I and photosystem II activity. The photochemical activity of fixed
      thylakoids is highly resistant to 1% triton. This indicates that fixed thylakoids
      may be useful starting material for isolation of functional components which can
      be related to the original structure of the membrane.

PMID- 16657100
TI  - Sodium and potassium absorption by bean stem tissue.
AB  - The effect of various periods of pretreatment in CaSO(4) solutions (aging) on the
      absorption of Na and K by bean stem slices was investigated. Freshly sliced
      tissue absorbed Na over the entire range of concentrations studied (0.02-50 mm).
      Potassium absorption by fresh tissue was nil at concentrations below 0.5 mm but
      at higher concentrations was similar to that of Na. When tissue was aged by
      aerating slices for 20 hr in 0.5 mm CaSO(4), K absorption was substantial over
      the entire range (0.01-50 mm), with evidence of a dual mechanism of absorption,
      whereas Na absorption was nil at concentrations below 0.2 mm. The formation of K
      absorbing capacity with aging, and the loss of Na-absorbing capacity at low
      concentrations, were temperature-dependent and did not result from significant
      changes in rates of efflux of either ion. The absorption of Na by fresh tissue
      and K by aged tissue was sensitive to antimetabolites, with K uptake the more
      sensitive. Benzyladenine, an analog of kinetin, suppressed the formation of K
      absorbing capability in aged tissue but did not prevent the loss of Naabsorbing
      capacity. Possible mechanisms for this alteration in ion-specificity of transport
      mechanisms are discussed.

PMID- 16657101
TI  - Auxins and Gibberellin-like Substances in Parthenocarpic and Non-parthenocarpic
      Syconia of Ficus carica L., cv. King.
AB  - In the King cultivar of fig, the first crop is parthenocarpic, develops on
      previous year's growth, and a series of supernumerary ovules develops within the
      original ovules. The second crop, formed on current-season's growth, requires
      fertilization. To determine whether the 2 crops differed in types, and in
      patterns of concentrations of total ;free' auxins and acidic gibberellins, they
      were extracted from weekly fruit samples. Timing of the 3 peaks of total auxins
      and the single peak of gibberellins was identical in the 2 crops. The first auxin
      peak in both occurred at the end of fruit growth period I (first rapid growth
      period), the second shortly before the end of period II (period of slow growth),
      and the rise and fall in concentrations of the third peak accompanied the rise
      and fall of the fruit growth rate in period III. The end of period II was marked
      by the single gibberellin peak. Additional peaks before the first sampling dates,
      of auxins in the first crop, of gibberellins in the second, were indicated by
      high concentrations in the first samples and subsequent rapid decline. The same 4
      individual auxins appeared in both crops. Auxins I and II were highest in
      concentration in the first total auxin peak of both crops. In the second peak of
      the first crop, auxins II and III were highest, whereas in that peak of the
      second crop auxins II and IV were highest. Qualitative differences in
      gibberellins occurred in the 2 crops. In general, auxin concentrations were
      higher in the first than the second crop, and gibberellin concentrations higher
      in the second. High concentrations of gibberellins coincided with low ones of
      auxins, and vice versa.

PMID- 16657102
TI  - Inhibitory Effect of Carbohydrate on Flowering in Lemna perpusilla. I.
      Interaction of Sucrose With Calcium and Phosphate Ions.
AB  - Flowering in Lemna perpusilla 6746 grown on tenth-strength Hutner's medium under
      short days was inhibited by 30 mM sucrose, glucose or fructose, but not by
      mannitol. The inhibition by sucrose does not appear to be due to sucrose-induced
      acidification of the medium during growth, or to trace metal contaminants of the
      sugar. Inhibition was partially prevented by raising either Ca(2+) or phosphate
      to levels used in half-strength medium. Possible mechanisms for these effects are
      discussed.

PMID- 16657103
TI  - Studies on a Maize Mutant Sensitive to Low Temperature II. Chloroplast Structure,
      Development, and Physiology.
AB  - In the Zea mays L. mutant M11 grown in the dark at 15 degrees , the
      ultrastructure of the etioplast is abnormal. The pigment content of the
      etioplasts is reduced but the in vivo absorption characteristics suggest that the
      normal protochlorophyll (ide)-holochrome is present. The lowered synthetic
      ability of the etioplasts is not primarily due to a reduced complement of plastid
      ribosomes. The plastids of mutant M11 grown in the light at 15 degrees contain
      little pigment, are markedly deficient in ribosomes and their ultrastructure is
      abnormal. In mutant M11 grown at 15 degrees , an extreme sensitivity of the
      plastid membranes to light was observed.

PMID- 16657104
TI  - Biosynthesis of Mustard Oil Glucosides: Sodium Phenylacetothiohydroximate and
      Desulfobenzylglucosinolate, Precursors of Benzylglucosinolate in Tropaeolum
      majus.
AB  - The biosynthesis of the mustard oil glucoside, benzylglucosinolate, was studied
      in Tropaeolum majus L. A number of labeled compounds were administered to plant
      shoots and the incorporation of tracer into benzylglucosinolate, isolated as the
      crystalline tetramethyl-ammonium salt, was measured. In order of decreasing
      efficiency of conversion into benzyl-glucosinolate the compounds fed were S-(beta
      d-glucopyranosyl)phenylacetothiohydroximic acid (desulfobenzylglucosinolate),
      sodium phenylacetothiohydroximate, dl-phenylalanine, d-glucose, and sodium-d-1
      glucopyranosyl mercaptide (1-thioglucose). The results are consistent with the
      hypothesis that the thioglucosyl group of benzylglucosinolate is derived by
      glucosylation of phenylacetothiohydroximate and not from 1-thioglucose. The
      results also suggest that benzylglucosinolate is formed by sulfation of
      desulfobenzylglucosinolate as the final step in its biosynthesis.A method for the
      isolation of a number of glucosinolates (mustard oil glucosides) is described
      which utilizes anion exchange chromatography on diethylaminoethyl (DEAE)
      cellulose. Potassium allylglucosinolate, tetramethylammonium benzylglucosinolate,
      potassium 2-hydroxy-2-phenylethylglucosinolate and potassium 2
      phenylethylglucosinolate were obtained on recrystallization of the glucosinolate
      fraction eluted from the column.

PMID- 16657105
TI  - The Occurence of delta-Tocopherylquinone in Higher Plants and Its Relation to
      Senescence.
AB  - delta-Tocopherylquinone (deltaTQ) content was determined in tobacco and yellow
      maple leaves, green ivy leaves and cactus tissues. It was found that the
      concentration of delta-TQ was highest in mature or senescent tissues, such as
      white tobacco leaves (0.02 mumole/g dry wt) while its detection was uncertain in
      young, green leaves from the apex of tobacco plants. Fractionation by
      centrifugation of senescent tobacco leaves showed that the osmiophilic globule
      fraction was enriched in delta-TQ. Electron microscope studies of young, mature
      and senescent tobacco tissues showed progressive changes in the size and number
      of osmiophilic globules. After chloroplast breakdown in senescent tobacco leaves,
      these globules became the predominant constituents of the organelle. delta-TQ
      which is associated with osmiophilic globules may play a role in the development
      of plants, particularly during senescence.

PMID- 16657106
TI  - Nucleoside Diphosphate-sugar 4-Epimerases I. Uridine Diphosphate Glucose 4
      Epimerase of Wheat Germ.
AB  - Uridine diphosphate (UDP)-glucose 4-epimerase (EC 5.1.3.2) has been purified over
      1000-fold from extracts of wheat germ by MnCl(2) treatment, (NH(4))(2)SO(4)
      fractionation, Sephadex column chromatography, and adsorption onto and elution
      from calcium phosphate gel. The enzyme has a pH optimum of 9.0. Km values are 0.1
      mm for UDP-d-galactose and 0.2 mm for UDP-d-glucose. NAD is required for
      activity; K(a) = 0.04 mm. NADH is an inhibitor strictly competitive with NAD;
      K(i) = 2 mum. Wheat germ also contains UDP-l-arabinose 4-epimerase (EC 5.1.3.5)
      and thymidine diphosphate (TDP)-glucose 4-epimerase which are distinct from UDP
      glucose 4-epimerase.

PMID- 16657107
TI  - Chilling injury and changes in adenosine triphosphate of cotton seedlings.
AB  - Young Gossypium hirsutum L. seedlings chilled at 5 degrees showed a continual
      decrease in ATP concentration with time of chilling. Chilled plants returned to
      optimum conditions were able to restore the initial ATP concentration when
      chilled only 1 day, but not when chilled 2 days. The decrease in ATP with
      chilling was prevented by hardening the seedlings at 15 degrees for 2 days (14-hr
      day-length) immediately before chilling. The ATP level of hardened plants was
      higher than of unhardened plants. When hardened plants were chilled at 5 degrees
      , the ATP level increased in the leaves but decreased in the roots.A mechanism of
      chilling injury is discussed in relation to the decrease in ATP concentration at
      low temperature.

PMID- 16657108
TI  - Ficin-Catalyzed Reactions. Hydrolysis of alpha-N-Benzoyl-l-Arginine Ethyl Ester
      and alpha-N-Benzoyl-l-Argininamide.
AB  - The effect of pH on the hydrolysis of alpha-N-benzoyl-l-arginine ethyl ester
      (BAEE) and alpha-N-benzoyl-l-argininamide (BAA) by a proteolytic enzyme component
      purified from Ficus carica var. Kadota latex has been studied in detail over the
      pH range of 3 to 9.5. k(cat) (lim) values for the hydrolysis of BAEE and BAA were
      essentially identical (5.20 and 5.01 sec(-1), respectively at 30 degrees ).
      k(cat) values for hydrolysis of BAEE and BAA were dependent on prototropic groups
      with apparent pK values of 4.24 and 8.53 and 4.10 and 8.59, respectively. k(cat)
      (lim) values for tht hydrolysis of BAEE and BAA were essentially identical (5.20
      and groups of pK 4.33 and 8.60 and 4.55 and 8.51, respectively. Thus the pH
      optimum is 6.5 for both substrates. K(m) (app) values for BAEE and BAA were 3.32
      x 10(-2)m and 6.03 x 10(-2)m respectively over the pH range of 3.9 to 8.0. These
      data are interpreted in terms of the involvement of a carboxyl and a sulfhydryl
      group in the active center of the enzyme. The data do not support the concept
      that deacylation of the acyl-enzyme is completely the rate controlling step in
      the hydrolyses. Rather, it appears that the magnitude of k(2) and k(3) are not
      greatly different.

PMID- 16657109
TI  - Modification of 2,4-dichlorophenoxyacetic Acid movement in bean petioles by
      light.

PMID- 16657110
TI  - Cotyledon expansion as a bioassay for cytokinins.

PMID- 16657111
TI  - The synthesis of ribulose-1,5-diphosphate carboxylase and chlorophyll in
      virescent cotton leaves.

PMID- 16657112
TI  - Changes in photosensitive stem growth in intact peas following irradiation.
AB  - Etiolated pea seedlings given a short red-light pretreatment followed by 30 hr of
      darkness no longer showed a typical red-light inhibition of internode elongation.
      The induction of phytochrome-insensitive growth was itself mediated by
      phytochrome, since far-red light reversed the effect of the short red-light
      pretreatment. Peas grown in white light showed a similar insensitivity to red
      light. However, in this instance the phytochrome system exerted some control over
      internode elongation since far-red light promoted growth slightly, and this
      effect was red-reversible.The loss of sensitivity to red light was correlated
      with a decrease in the amount of spectrophotometrically assayable phytochrome.
      However, the loss of phytochrome occurred in a relatively short time compared to
      the period necessary to attain maximal insensitive growth (2 hr versus about 30
      hr). Also, after the red-light and dark pretreatment, although 40% of the
      original amount of phytochrome remained, red light had no effect on elongation.
      Neither loss of phytochrome nor loss of red-light sensitive growth was observed
      at 0 to 1 degrees .

PMID- 16657113
TI  - Ethylene-controlled Induction of Phenylalanine Ammonia-lyase in Citrus Fruit
      Peel.
AB  - l-Phenylalanine ammonia-lyase (PAL) activity is low in the external layers
      (flavedo) of intact mature grapefruit peel. Flavedo discs evince upon incubation
      increasing PAL activity and ethylene production. Light has no effect in enhancing
      PAL activity in discs. Exogenous ethylene stimulates PAL activity in the flavedo
      of intact mature grapefruits (half maximum stimulation at 15 ppm); such activity
      rapidly decreases when fruit is removed from the ethylene containing atmosphere.
      Carbon dioxide inhibits both ethylene production and PAL activity of discs;
      exogenous ethylene only partly relieves PAL inhibition. Cycloheximide inhibits
      both PAL activity and ethylene production by flavedo discs. The same
      concentration of cycloheximide also inhibits PAL activity of discs in the
      presence of exogenous ethylene. Protein synthesis seems therefore to be needed at
      both levels of ethylene evolution and enhancement of PAL activity.

PMID- 16657114
TI  - Nitrogen Assimilation and Protein Synthesis in Wheat Seedlings as Affected by
      Mineral Nutrition. II. Micronutrients.
AB  - Activity of nitrate reductase from Triticum aestivum L. seedlings was decreased
      by deficiencies of molybdenum, zinc, and chlorine. Nitrate accumulated in
      molybdenum-deficient seedlings, declined in zinc-deficient seedlings, and was
      unaffected by the other micronutrient treatments. Glutamic acid dehydrogenase
      activity was decreased by deficiency of molybdenum, the only nutrient that
      affected the enzyme. Glutamine synthetase activity was decreased only by copper
      deficiency, and glutamic-oxaloacetic transaminase was not affected by any
      micronutrient deficiencies. Incorporation of (14)C-leucine into protein by wheat
      seedlings was increased by molybdenum deficiency, apparently because of decreased
      inhibition from endogenous amino acids, and was decreased by copper deficiency.
      Protein content was not affected significantly by the micronutrient treatments.

PMID- 16657115
TI  - Susceptibility to Enzymatic Degradation of Cell Walls From Bean Plants Resistant
      and Susceptible to Rhizoctonia solani Kuhn.
AB  - Enzymes in culture filtrates of Rhizoctonia solani Kuhn grown using 4-day old or
      20-day old bean (Phaseolus vulgaris L.) hypocotyl cell walls as a carbon source
      degraded xylan, galactan, galactomannan, araban, polygalacturonic acid, and
      carboxymethylcellulose. Extracts of lesions from R. solani infected plants, but
      not healthy plants, contained similar enzymatic activities. These enzyme sources
      readily solubilized cell wall constituents containing arabinose, galactose, and
      glucose from 4-day old, but not from 20-day old, bean cell walls. Analysis of
      cell walls prepared from infected plants revealed that the alterations in cell
      wall composition in the diseased host were limited largely to the immediate
      lesion areas and occurred during the early phases of pathogenesis. The cell walls
      of young susceptible bean seedlings could be degraded by R. solani enzymes, but
      the cell walls of older plants which are resistant to this pathogen were not
      susceptible to enzymatic destruction by the same enzyme preparation.

PMID- 16657116
TI  - Photosynthetic Activity of Chloroplasts Isolated From Bermudagrass (Cynodon
      dactylon L.), a Species With a High Photosynthetic Capacity.
AB  - Chloroplasts have been isolated from bermudagrass (Cynodon dactylon L.) leaves
      and assayed for photophosphorylation and electron transport activity. These
      chloroplasts actively synthesize adenosine triphosphate during cyclic electron
      flow with phenazine methosulfate and noncyclic electron flow concurrent with the
      reduction of such Hill oxidants as nicotinamide adenosine dinucleotide phosphate,
      cytochrome c, and ferricyanide. Apparent Km values for the cofactors of
      photophosphorylation have been determined to be 5 x 10(-5) M for phosphate and
      2.5 x 10(-5) M for adenosine diphosphate. The influence of light intensity on
      photophosphorylation has been studied and the molar ratio of cyclic to noncyclic
      phosphorylation calculated. It is concluded that the high photosynthetic capacity
      of bermudagrass leaves probably could be supported by the photophosphorylation
      capacities indicated in these chloroplast studies and the anomalous lack of data
      in chlorolast studies on the production of sufficient reductant for CO(2)
      assimilation at high light intensities has been noted.

PMID- 16657117
TI  - Initial ATP Formation, NADP Reduction, CO(2) Fixation, and Chloroplast Flattening
      Upon Illuminating Pea Leaves.
AB  - Chloroplasts in living cells of detached and sectioned leaves of Pisum sativum
      had a thickness of 2.68 +/- 0.04 mu in the dark as determined from photographs
      made using a phase contrast microscope. Upon illumination with 4000 lux for 10
      min, the chloroplasts flattened to 2.15 +/- 0.04 mu. There was a short lag period
      of about 11 sec at 1000 lux and 2 sec at 4000 lux before appreciable light
      induced flattening occurred. Both ATP and reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) in detached pea leaves increased upon illumination
      and then fell during the initial 60 sec. The maximum ATP level was attained in 16
      sec at 1000 lux and 10 sec at 4000 lux, while NADPH required about twice as long
      to reach a maximum. A sustained rate of carbon dioxide fixation occurred after a
      lag period coinciding in time with the drop in the NADPH level. ATP appeared to
      be involved not only with carbon dioxide fixation, but also with some reaction
      beginning sooner, perhaps the light-induced chloroplast flattening. Considering
      the initial photophosphorylation and the sustained CO(2) fixation rates, the ATP
      formation rate in vivo apparently increased after the leaves had been in the
      light for a few min.

PMID- 16657118
TI  - Determination of the Rate of CO(2) Evolution by Green Leaves in Light.
AB  - The rate of CO(2) evolution in light by green leaves was determined by 2 methods
      in a closed system of gas analysis and by measuring the amount of CO(2) evolved
      into a CO(2) free air stream in an open system. All methods gave similar results
      under comparable conditions.A light stimulated CO(2) evolution from green leaves
      was found in all the plant species studied except corn where there was no
      apparent CO(2) evolution in the light.The magnitude of CO(2) evolution in light
      was markedly dependent on air flow rate and light intensity. At high light
      intensity and high flow rate, the rate of CO(2) evolution from green leaves was
      1.4 to 1.7 times greater than that in darkness.

PMID- 16657119
TI  - Effects of Temperature on Photosynthesis and CO(2) Evolution in Light and
      Darkness by Green Leaves.
AB  - Using an open and a closed system of gas analysis, it was found that CO(2)
      evolution in light and in darkness from plant leaves (sunflower, soybean,
      watermelon, eggplant, and jackbean) have a different response to temperature.
      While the rate of CO(2) evolution in light increased with increasing temperature
      from 17 to 35 degrees and then declined, the rate of CO(2) evolution in darkness
      increased continuously up to 40 degrees . The rate of CO(2) evolution in light
      was affected by light intensity. At 1800 ft-c and below 35 degrees the rate of
      CO(2) evolution in light was greater than in darkness, but above 35 degrees it
      became lower than in darkness. The Q(10) for CO(2) evolution in light was
      consistently lower than that in darkness.Apparent photosynthesis decreased with
      increasing temperature, from 20 to 40 degrees and its rate was affected by both
      light intensity and oxygen concentration. In leaves of dicotyledonous plants
      studied the decrease in apparent photosynthesis between 20 to 30 degrees at 21%
      O(2) was shown to be due primarily to an increase in CO(2) evolution in light
      with relatively little effect on photosynthesis.In corn which does not evolve
      CO(2) during illumination there was little effect of increasing temperature on
      the rate of apparent photosynthesis.The different response to temperature of
      CO(2) evolution in light and in darkness support the earlier conclusion that
      these are 2 different processes.

PMID- 16657120
TI  - Photosynthesis: action spectra for leaves in normal and low oxygen.
AB  - The action spectrum of apparent photosynthesis for attached radish (Raphanus
      sativus L. var. Early Scarlet Globe) and corn (Zea mays L. var. Pride V.) leaves
      was measured at 300 mul/l CO(2) and both 21% and 2% O(2). The spectra were
      measured at light intensities where apparent photosynthesis was proportional to
      intensity. For radish, a high compensation point plant, oxygen had an inhibiting
      effect on photosynthesis at all wavelengths from 402 to 694 mmu. If a constant
      rate of photosynthesis at 21% O(2) for the different wavelengths was chosen, then
      the percent increase in net CO(2) fixation at 2% O(2) was constant. For corn, a
      low compensation point plant, no inhibitory effect of oxygen concentration from
      2% to 21% O(2) was found over the visible spectrum. The CO(2) compensation point
      for light intensities greater than the light compensation point was found to be
      constant and independent of wavelength for both radish and corn leaves. For
      radish, the lowering of the oxygen concentration from 21% to 2% at these
      intensities was found to reduce the CO(2) compensation point by the same amount
      for the wavelengths studied.

PMID- 16657121
TI  - Effects of Phenylmercuric Acetate on Stomatal Movement and Transpiration of
      Excised Retula papyrifera Marsh. Leaves.
AB  - Effects of 10(-3)m, 10(-4)m, and 10(-5)m phenylmercuric acetate (PMA) on stomatal
      movement and transpiration of excised Betula papyrifera leaves were investigated.
      Duco cement leaf prints and transpiration decline curves were used for the
      analysis of stomatal condition. PMA induced stomatal closure and decreased
      transpiration. Stomata of leaves treated with any of the 3 PMA concentrations
      closed earlier and at a higher relative water content than did stomata of
      untreated leaves. As determined from transpiration decline curves, PMA at 10(-3)m
      caused an increase in apparent "cuticular" transpiration. However, the increase
      appeared to result largely from some PMA-poisoned stomata which remained open for
      prolonged periods. Considerable PMA toxicity was observed, with 10(-3)m and 10(
      4)m concentrations causing browning of leaves. PMA treatment caused a decrease in
      chlorophyll content, even at a low PMA concentration (10(-5)m) which influenced
      stomatal response only slightly and did not cause evident browning of leaves. The
      time and degree of stomatal opening varied with stomatal size. Large stomata
      tended to open earlier and close later than small stomata. Hence, in Betula
      papyrifera stomata of various size classes were considered as physiologically
      different populations.

PMID- 16657122
TI  - Effect of adsorbed cations on phosphorus uptake by excised roots.
AB  - Pretreatment of excised roots of Hordeum vulgare, Zea mays, and Glycine max with
      various salt solutions affected their subsequent rate of phosphorus absorption
      from 2 x 10(-5)m KH(2)PO(4). The rate of absorption was greatest for roots
      pretreated with trivalent cations, intermediate with divalent cations and lowest
      with monovalent cations. It appeared that the pretreatment involved a rapid
      exchange reaction at the root surface which was reversible. A 1 min pretreatment
      was effective for more than 20 min. The acceleration of phosphorus uptake by
      roots produced by polyvalent cations may be due partly or entirely to a greater
      reduction in the electrical potential at the root surface or within the pores of
      the negatively charged cell wall by polyvalent cations than by monovalent
      cations.

PMID- 16657123
TI  - Distribution of calcium absorbed by all or part of the root system of beans.
AB  - When either the whole root system or a single root of the bean plant (Phaseolus
      vulgaris L.), at different stages of maturity, was fed (45)Ca for a period of 6
      hr, the leaves exhibited a definite pattern of (45)Ca acquisition with maximum
      acquisition for the primary, first, second, and third trifoliolate leaves at 12,
      16, 18, and 22 days of growth, respectively. This maximum acquisition occurred
      when a leaf approached full expansion. A liquid scintillation spectrometer was
      employed for (45)Ca analysis.Autoradiograms indicated that when (45)Ca was
      applied to the terminal 5 cm portion of specific lateral roots for a period of 6
      hr, specific areas of the shoot were preferentially supplied with (45)Ca. The
      amount of (45)Ca transported upward, when the terminal 5 cm portion of a single
      lateral root was treated, greatly decreased in plants older than 20 days, and the
      growth rate of these roots was also reduced at about the same time. When the
      whole lateral root was involved in (45)Ca uptake, the amount of (45)Ca
      transported to the shoot increased with increasing plant age until after day 22.
      A continuous increase in (45)Ca transport to the shoot occurred when the whole
      root system was subjected to (45)Ca treatment. One factor involved in the
      decreased movement of (45)Ca into a particular leaf may be a decreased absorptive
      capacity of that part of the root which preferentially supplies Ca to this leaf.
      Other possible factors are discussed.

PMID- 16657124
TI  - Sugar transport in conducting elements of sugar beet leaves.
AB  - Autoradiography was used to determine the distribution of labeled sugar in
      conducting elements of the blade and petiole of sugar beet leaves at intervals
      ranging from 5 sec to 24 hr. The processes of assimilation by the green cells,
      collection of sugar in the minor veins and export in phloem elements were
      demonstrated visually. It appears that in minor veins sugar is translocated in
      companion cells rather than sieve tubes. In major veins translocation occurs in
      sieve tubes.

PMID- 16657125
TI  - Metabolism of barley seed during early hours of germination.
AB  - The growth process in germinating barley seeds and its inhibition by actinomycin
      D and puromycin were investigated. Soon after seeds are imbided, their
      respiratory activity increases several fold, and the protein- and carbohydrate
      synthesizing systems become active. The immediate activation of protein synthesis
      and its inhibition by actinomycin D and puromycin suggest that the dry seed has
      all the components necessary for protein synthesis.Although a good correlation
      exists between the rate of oxygen uptake and that of protein synthesis during the
      first 12 hr of germination, respiration appears to be independent of protein
      synthesis during the first 8 hr, as reflected by the insensitivity of the
      respiratory process to actinomycin D and puromycin. However, after 8 hr both
      antibiotics reduce oxygen uptake as well as subsequent seedling growth.The
      distribution of (14)C, derived from labeled glucose during the early hours of
      barley germination, among various fractions of metabolites, indicated that 50 to
      70% of the utilized glucose appeared in (14)CO(2). The rest of the incorporated
      label appeared in hemicelluloses and starch, water-soluble ethanol-insoluble
      carbohydrates, and to a lesser extent in proteins and cellulose.

PMID- 16657126
TI  - A Short-lived Intermediate Form in the in Vivo Conversion of Protochlorophyllide
      650 to Chlorophyllide 684.
AB  - When dark-grown leaves of Phaseolus vulgaris, Hordeum vulgare, Zea mays and Pisum
      sativum were irradiated for 3 sec at 2 degrees the first product of
      protochlorophyllide 650 conversion had an absorption maximum at 678 nm. This form
      was then converted in a dark reaction to chlorophyllide 684, the form generally
      observed and regarded as the in vivo product of the photoreaction. The dark
      conversion at 2 degrees was complete in 6 to 10 min in the various plants. The
      time course of the dark reaction was followed at 690 nm near the maximum of the
      difference spectrum for the conversion. There was a constant relationship between
      the initial amount of chlorophyllide 678 and the final amount of chlorophyllide
      684. The rates of the dark reaction at 2 degrees varied 3-fold among the plants
      treated. The reaction was not first order. At 25 degrees the reaction followed at
      690 nm was complete in 20 to 60 sec. Q(10)'s varied from 2.8 to 3.7 between 2
      degrees and 25 degrees . Phytochrome absorbancy changes were shown to be too low
      to interfere with these measurements except in pea leaves. In a subsequent stage
      of greening newly regenerated protochlorophyllide went through the same sequence
      upon photoconversion. Chlorophyllide 678 probably corresponds to the product
      formed in vitro from the protochlorophyllide holochrome. The dark reaction
      appears to represent the first interaction between the photoconverted holochrome
      and other elements of the proplastid. The lack of this dark reaction could also
      account for the spectral properties of certain albino mutants.

PMID- 16657127
TI  - Translocation of sugars into infected cabbage tissues during clubroot
      development.
AB  - Sucrose, glucose, and inositol were the major sugars in cabbage hypocotyls
      infected by Plasmodiophora brassicae and in noninfected hypocotyls, based on
      paper, thin-layer, and gas-liquid chromatography. Small amounts of trehalose were
      tentatively identified in extracts from noninfected hypocotyls, whereas up to 20x
      this level occurred in extracts from infected hypocotyls. Inositol declined in
      the infected hypocotyls while glucose increased to about 4x the level in
      noninfected hypocotyls. Fructose and mannose concentrations increased about 2
      fold in the diseased hypocotyls, whereas the galactose concentration was about
      one-third that of noninfected hypocotyls.Translocation of (14)CO(2) sugar
      photosynthates into infected hypocotyls was more rapid than that into noninfected
      hypocotyls. The infected tissues also exported less sugar than the non-infected
      tissues. Sucrose was the major sugar translocated into the hypocotyls of both
      infected and noninfected plants.

PMID- 16657128
TI  - Potato sucrose synthetase: purification, properties, and changes in activity
      associated with maturation.
AB  - Sucrose synthetase activity is high in young potato tubers but decreases markedly
      during maturation. The activity decreases rapidly after the tubers are harvested
      and remains low regardless of storage temperature. This enzyme was purified 34
      fold from freshly harvested immature potatoes. It catalyzes both cleavage and
      synthesis of sucrose but the 2 activities differ in a number of ways. The pH
      optima are 6.6 and 8.8 for sucrose cleavage and synthesis. respectively. Sucrose
      cleavage is activated 4-fold by mercaptoethanol and is inhibited by Mn(2+). In
      contrast, sucrose synthesis is activated only slightly by either mercaptoethanol
      or Mn(2+) alone but 2-fold in the presence of both reagents. However, it was not
      possible to resolve the 2 activities, their stabilities to partial thermal
      inactivation are identical, and their ratios are constant over a wide range of
      activities.

PMID- 16657129
TI  - Enzymic Mechanism of Starch Breakdown in Germinating Rice Seeds II. Scutellum as
      the Site of Sucrose Synthesis.
AB  - In a close parallel to the developmental pattern of alpha-amylase activity, a
      rapid increase of maltase activity occurred in the endosperm tissue of
      germinating rice seeds after about 4 days of the seed imbibition. The overall
      pattern of the 2 hydrolytic enzyme activities strongly suggest that amylolytic
      breakdown is the major metabolic route of starch utilization in the germinating
      rice seeds. Results of the chemical analyses of sugar constituents as well as the
      measurements of sucrose synthetase activity show that the scutellum is the site
      of sucrose synthesis in the germinating rice seeds. It is thus supported that
      glucose derived from the reserve starch in endosperm is transported to scutellum,
      where it is converted to sucrose. Sucrose is further mobilized to the growing
      tissues, shoots and roots.

PMID- 16657130
TI  - Metabolism of C-Maltose in Avena fatua Seeds During Germination.
AB  - Non-dormant and dormant seeds of Avena fatua metabolize (14)C-maltose in
      different ways: in non-dormant seeds, (14)C-maltose administered to the endosperm
      is readily converted to sucrose in the scutellum and translocated to the embryo;
      in dormant seeds, little sucrose is synthesized from (14)C-maltose, and maltose
      and glucose tend to accumulate in the endosperm. It is suggested that
      biosynthesis of sucrose is essential for effective transport of the endosperm
      reserve to the embryonic axis in germinating seeds.

PMID- 16657131
TI  - Changes in Succinyl CoA Synthetase Activity in Etiolated Bean Leaves Caused by
      Illumination.
AB  - The illumination of etiolated bean leaves (Phaseolus vulgaris) causes an increase
      in the activity of succinyl coenzyme A synthetase. Continuous white light or
      short periods of red or blue light followed by darkness will induce an increase
      with the highest activity at about 6 hr after the onset of illumination.
      Thereafter the activity decreases so that at 12 hr it is the same as the initial
      dark activity. Treatment with cycloheximide before illumination prevents the
      increase in activity. A number of other enzymes have been studied in an attempt
      to determine the significance of the transient nature of the changes in succinyl
      CoA synthetase activity.

PMID- 16657132
TI  - Delta-aminolevulnic Acid dehydrase in greening bean leaves.

PMID- 16657133
TI  - Turion Induction in Spirodela polyrrhiza by Abscisic Acid.

PMID- 16657134
TI  - Metabolism of carbon-14-labeled benzene and tolueue in avocado fruit.

PMID- 16657135
TI  - Characterization and Role of an Endogenous Inhibitor in the Induction of Cold
      Hardiness in Acer negundo.
AB  - An inhibitor extracted from short day treated Acer negundo leaves was compared to
      abscisic acid in 4 different solvent systems. The chromatographic properties of
      abscisic acid and the inhibitor were in very close agreement. Treatment of Acer
      negundo plants under non-hardening preconditions (long days) with either the
      inhibitor or abscisic acid increased hardiness after a hardening period of 3
      weeks at 40 degrees . A gibberellin-inhibitor relationship was further studied by
      making comparison of extracts of plants subjected to either 4 weeks of long days,
      long days + 5 degrees nights, or short days. These tests indicated that
      gibberellin-like activity was greatest when the treatment included long days.
      Abscisic acid-like levels were highest when the treatments consisted of short
      days or long days + 5 degrees nights. Since the latter groups are the most
      capable of developing hardiness, the hardening process appears to be more closely
      related to a build-up of abscisic acid levels than a reduction of gibberellin
      levels.

PMID- 16657136
TI  - Action of Phytochrome During Prechilling of Amaranthus retroflexus L. Seeds.
AB  - Dark germination of Amaranthus retroflexus L. seeds at 35 degrees increased after
      several days of prechilling at 20 degrees or lower. Irradiation with far-red
      light for short periods during the early hours of a prechilling period at 10
      degrees inhibited subsequent dark germination at 35 degrees . The inhibition was
      completely reversible with red light. Far-red irradiation in the latter part of
      the prechilling period was less effective. Increased dark germination of A.
      retroflexus seeds following a prechilling period at 20 degrees or less is
      attributed to action of preexistent P(FR), the far-red absorbing form of
      phytochrome, within the seeds. Inactivation of P(FR) was found to proceed ca. 4
      times more rapidly at 25 degrees than at 20 degrees . Failure of imbibition
      temperatures above 20 degrees to increase dark germination of A. retroflexus
      seeds is attributed to the rapid thermal reversion of pre-existent P(FR). We
      suggest that the action of prechilling (layering) on many other seed kinds arises
      in a similar way.

PMID- 16657137
TI  - Leaf water balance during oscillation of stomatal aperture.
AB  - Continuous transpiration and beta-guage measurements were made on cotton plants,
      the stomatal apertures of which had been induced to oscillate, thus allowing a
      water balance to be made, and leaf potential to be measured as functions of
      time.Analyses showed phase differences between the water entering and leaving the
      leaf. Also, from the phase relationship between the flow into the leaf and the
      water potential in the leaf it was shown that the water potential in the xylem of
      the plant also oscillated. This is proposed as a necessary condition for the
      stomates of all the leaves of a plant to oscillate in phase.It is convenient to
      describe the dynamics of the phenomena using a simple electrical analogue, and
      the usefulness and limitations of the model are discussed.

PMID- 16657138
TI  - Effects of picloram and ethylene on leaf movement in huisache and mesquite
      seedlings.
AB  - Application of 4-amino-3,5,6-trichloropicolinic acid (picloram) to roots
      stimulated the production of ethylene in both mesquite [Prosopis juliflora
      (Swartz) DC. var. glandulosa (Torr.) Cockerell] and huisache [Acacia farnesiana
      (L.) Willd.] seedlings. Herbicide levels rose in tissues before we detected
      increased ethylene production. Rates of ethylene production by various parts of
      the plant paralleled herbicide concentrations. In both species, picloram caused
      loss of leaf movement and epinastic curvature of leaves and stems. Only huisache
      was defoliated by picloram. Rates of ethylene production increased before we
      observed any leaf movement or defoliation responses. Fumigation of plants with
      levels of ethylene, calculated to approximate those in herbicide-treated plants
      at the initial loss of leaf movement, caused the same symptoms as picloram
      treatment. The time sequence of ethylene fumigation and loss of the ability for
      leaf movement is compatible with the hypothesis that there is a causal
      relationship between picloram and ethylene production and loss of leaf movement.

PMID- 16657139
TI  - The osmotic behavior of corn mitochondria.
AB  - The volume changes undergone by corn (Zea mays L.) mitochondria suspended in
      solutions of constant or varying osmolarity were studied. Within the range of
      osmotic pressure from 1.8 to 8.4 atmospheres, corn mitochondria behave as
      osmometers, if allowance is made for an osmotic "dead space" of about 6.9 mul/mg
      protein. The final equilibrium volume of mitochondria swollen in solutions
      containing both ribose and sucrose were shown to depend upon the concentration of
      impermeable solute (sucrose) present and not upon the concentration of ribose
      present. Osmotic reversibility was found for mitochondria swollen in isotonic
      solutions of KCI or ribose. The passive swelling of corn mitochondria may be due
      to the osmotic flow of water coupled to the diffusion of a permeable solute.

PMID- 16657140
TI  - The kinetics of amiben absorption and metabolism as related to species
      sensitivity.
AB  - The rates of absorption and metabolism of 3-amino-2,5-dichlorobenzoic acid
      (amiben) were investigated in 3-day-old roots of amiben-sensitive velvetleaf
      (Abutilon theophrasti Medic.) and amiben-tolerant morningglory [Ipomoea hederacea
      (L.) Jacq.].The initial rates of amiben absorption and binding were identically
      concentration dependent for both species for external concentrations from 0.02 to
      500 mg/liter.THE RATES AT WHICH THE ABSORBED AMIBEN WAS: 1) bound; 2)
      incorporated into an unidentified amiben complex (amiben-X) and N-(3-carboxy-2,5
      dichlorophenyl)-glucosylamine (N-glucosyl amiben); and 3) accumulated in these
      tissues during a 24-hr period was investigated at widely different concentrations
      for both species. There were no salient differences between the species in their
      amiben absorption rate at 5 mg/liter, but the absorbed amiben was complexed as N
      glucosyl amiben more rapidly and to a greater extent in morningglory; maximum
      rate of glucosylation was attained earlier after exposure to amiben in
      morningglory than in velvetleaf. At nearly equitoxic concentrations (100 and 1
      mg/l, 5 and 0.05 mg/l for morningglory and velvetleaf, respectively), the rates
      at which the absorbed amiben was distributed among N-glucosyl amiben, amiben-X
      and amiben were very similar for both species, although morningglory absorbed
      amiben at the faster rate. At amiben concentrations required for equal expression
      of the herbicidal effect, morningglory conjugates amiben at a faster rate and
      tolerates higher levels of free amiben than velvetleaf. Amiben toxicity in a
      species is expressed at that concentration which saturates the glucosylation
      process, and results in amiben accumulation at sufficiently high levels to exert
      its toxic effect. A scheme for amiben metabolism in plants is presented.

PMID- 16657141
TI  - Crystalloids of phycomyces sporangiophores: nature and photosensitive
      accumulation.
AB  - Crystalloids accumulate in the vacuoles of the giant sporangiophores of
      Phycomyces blakesleeanus Burgeff during growth. On the basis of solubility in
      alkaline solutions, cytochemical staining reactions, trypsin sensitivity, optical
      absorption and response in the Lowry protein test, the crystalloids have been
      judged to consist principally of an acidic protein. In assays by Lowry test and
      by reference to optical absorption at 280 mmu, dark-grown sporangiophores were
      consistently found to contain from 2 to 4 times as much crystalloid material as
      light-grown counterparts. Concurrent assays of soluble phenolic materials
      revealed no significant effect of culture illumination, while carotene content of
      sporangiophores and mycelium was found to be raised from 2 to 4-fold by
      illumination during growth.

PMID- 16657142
TI  - Design calibration and field use of a stomatal diffusion porometer.
AB  - Modifications of the design and calibration procedure of a diffusion porometer
      permit determinations of stomatal resistance which agree well with results
      obtained by leaf energy balance. The energy balance and the diffusion porometer
      measurements indicate that the boundary layer resistances of leaves in the field
      are substantially less than those predicted from heat transport formulas based on
      wind flow and leaf size.

PMID- 16657143
TI  - Abscission of cotton flower buds and petioles caused by protein from boll weevil
      larvae.
AB  - Protein extracted from boll weevil larvae causes abscission of cotton flower buds
      and debladed petioles. Abscission of buds is preceded by a rapid and persistent
      flaring of bracts; cell proliferation is induced in the abscission zone of
      debladed petioles. A possible mode of transmission of the agent from larva to bud
      tissue is discussed.

PMID- 16657144
TI  - Imbibition temperature sensitivity of lima bean seeds controlled by initial seed
      moisture.
AB  - Excised embryonic axes and whole seeds of Phaseolus lunatus L. were previously
      shown to be injured if exposed to low (5 degrees -15 degrees ) temperature during
      the initial stages of imbibition. Present data show that this chilling injury
      during imbibition of liquid water can be prevented if axes are first allowed to
      absorb water vapor. The increase of initial water content to 20% increases growth
      even of unchilled axes, and reduces leaching of 264 mmu absorbing compounds.
      Protection resulting from increased water content is at first independent of the
      temperature at which water vapor was absorbed. However, longer exposure of high
      moisture axes to low temperature results in typical chilling injury. The response
      to initial seed moisture is repeatedly reversible with changes in water content.
      Because the same response occurs in intact seeds, it may be possible both to
      protect them against low temperature injury and to increase vigor by increasing
      seed water-content prior to planting.

PMID- 16657145
TI  - Direct relation between growth and frost hardening in cabbage leaves.
AB  - Potted cabbage plants were grown in growth chambers at 25 degrees day and 15
      degrees night and hardened successively at 5, 0, and -3 degrees . Leaf growth was
      determined by measuring leaf area, hardiness by freezing at a series of
      temperatures and determining percent survival. Leaf growth increased progessively
      with leaf number, reaching a maximum rate of growth and final area in the tenth
      and eleventh leaves when the plants become potbound. Leaf growth continued at
      hardening temperatures of 5 or 0 degrees , the Q(10) being 2.0 to 2.5. Ability to
      harden also increased with leaf number, paralleling the growth rate of the leaves
      just before hardening as well as the growth rate and the total growth during
      hardening. The above results were similar whether prolonged (several weeks) or
      brief (24 hr) hardening was utilized.

PMID- 16657146
TI  - Light as a source of error in estimates of water potential by vapor
      equilibration.

PMID- 16657147
TI  - Photosynthetic Properties of ac-31, a Mutant Strain of Chlamydomonas reinhardi
      Devoid of Chloroplast Membrane Stacking.
AB  - A pale-green mutant strain of Chlamydomonas reinhardi, ac-31, is characterized by
      the absence of any stacking of its chloroplast membranes. The capacity for
      photosynthetic electron transport, phosphorylation, and CO(2) fixation in ac-31
      is substantial, and it is concluded that these photosynthetic activities occur
      within the single membrane. The photosynthetic capacities of wild type and ac-31
      as a function of increasing light intensity are compared. Saturation is attained
      at higher light intensities in ac-31, and the kinetics of the 2 sets of curves
      are distinctly different. The possibility that energy transfer is enhanced by
      membrane stacking is suggested by these results. The repeatedly-observed
      correlation between reduced stacking and disfunctional Photosystem II activities
      is discussed in view of the observation that ac-31 has no stacking but retains a
      functional Photosystem II.

PMID- 16657148
TI  - Short term influx as a measure of influx across the plasmalemma.
AB  - It is shown that the influx of tracer to a plant cell must be measured for less
      than one third of the half-time for exchange of cytoplasmic tracer, and any
      subsequent wash must be negligibly brief, if the initial influx measured over a
      finite period is to be a good estimate of the plasmalemma influx. Complications
      due to lack of knowledge of the cytoplasmic exchange rate constant and to
      extracellular contents make it difficult to make such an estimate from influx
      measurements alone. The use of influx measurements is further discussed.

PMID- 16657149
TI  - Magnesium nutrition of two species of sunflower.
AB  - Helianthus annuus L., the common cultivated sunflower, and Helianthus bolanderi
      Gray subspecies exilis Heiser, a form endemic on serpentine soils, were grown in
      culture solutions with widely varying Mg levels. For comparable development, H.
      bolanderi exilis required higher levels of Mg in the solution than H. annuus,
      both in the range of visual deficiency symptoms and in higher ranges.With 0.5 mm
      Ca in the solutions, H. annuus reached a plateau in yield in the range of 0.25 to
      2.0 mm Mg in the solution, then declined in weight markedly as Mg was increased
      further. This decline was probably caused by the marked "luxury" consumption of
      Mg. Conversely, H. bolanderi exilis increased steadily in yield as Mg was raised
      up to 10 mm and tolerated up to 50 mm Mg in the solution with only about 30%
      decline in yield. The increasing yield of H. bolanderi exilis in solutions of
      increasing Mg level is attributable to the steadily rising Mg content of the
      plants. A high level of external Mg is apparently needed to bring internal Mg to
      the sufficiency range. This characteristic of the species also serves to obviate
      luxury consumption of Mg, thus contributing to its tolerance of very high
      external levels of this ion.

PMID- 16657150
TI  - Metabolism of Glutamic Acid and N-Acetylglutamic Acid in Leaf Discs and Cell-free
      Extracts of Higher Plants.
AB  - Radioactive glutamic acid and N-acetylglutamic acid have been incubated with
      normal and wilted leaf discs and radioactivity recovered in uncombined proline.
      The discs which had been placed under moisture stress incorporated considerably
      more label in uncombined proline than did normal discs.In extracts of swiss chard
      leaves, both (14)C-N-acetylglutamic acid and glutamic acid are metabolized to
      their corresponding semialdehyde as evidenced by a recovery of proline after
      appropriate treatment. There is also incorporation of label in N(a)
      acetylornithine from N-acetylglutamic acid. These reactions require ATP, Mg(2+),
      and NADH or NADPH.

PMID- 16657151
TI  - Zea shoot development in response to red light interruption of the dark-growth
      period. I. Inhibition of first internode elongation.
AB  - Brief, low energy (approximately 400 Kerg cm(-2)) red light interruption of the
      early dark-growth period of Zea mays L. cv F-M Cross induced inhibition of first
      internode elongation which was maximal whenever light interruption occurred from
      2.5 to 4 days of seedling age. Two-thirds of the maximal inhibition occurred in
      the tissues constituting the region 0 to 2 mm below the coleoptilar node at time
      of light treatment. The coleoptile tip showed the greatest sensitivity for red
      light reception in the internode response. Far-red light exposures following red
      light treatments reversed the red light effect. However, far-red light alone
      inhibited first internode elongation as effectively as red light of similar
      dosage.

PMID- 16657152
TI  - The effect of salinity on the malic dehydrogenase of pea roots.
AB  - Effect of salinity on malate dehydrogenase activity was studied.Pea root tips
      contain 2 different malate dehydrogenases. One is located in the particulate,
      mitochondrial fraction, the other in the soluble, cytoplasmic fraction. Both can
      act when coupled with either NAD or NADP.Growing plants in Na(2)SO(4) salinated
      medium did not affect the pattern of the malate dehydrogenases in the root tips.
      Growing plants in NaCl salinated media resulted in the appearance of a new, third
      isoenzyme. This new isoenzyme was located in the cytoplasmic fraction.Salinity of
      both types, when present in growth medium, induced increases in the NADP coupled
      activity of the mitochondrial malate dehydrogenase. The NAD coupled activity,
      however, was depressed except in the cytoplasmic fraction of plants grown in
      media salinated with NaCl to 1 atmosphere. Addition of either of the salts to
      assay media of enzymes, isolated from plants grown in non salinated substrate,
      did not have any significant effect.

PMID- 16657153
TI  - Cytokinins from a variant strain of cultured soybean cells.
AB  - A strain of soybean cells capable of growing on a tissue culture medium lacking a
      cytokinin produced at least 3 compounds active in the soybean cytokinin assay.
      The characteristics of these compounds were consistent with their being zeatin in
      the free form, zeatin ribonucleoside and zeatin ribonucleotide. Although the
      conversion from a cytokinin dependent to independent condition in this strain
      parallels the change of normal cells to crown gall tumor state in terms of the
      capacity to synthesize cell division substances, the soybean factors are distinct
      from the nicotinamide derivatives reported for tumor cells of Vinca.

PMID- 16657154
TI  - Oligomycin inhibition of phosphate uptake and ATP labeling in excised maize
      roots.
AB  - ATP labeling by newly absorbed (32)P in excised maize roots was reduced 34% by
      the presence of oligomycin during a 4-min uptake period with no reduction in rate
      of phosphorus absorption. Longer exposure to oligomycin, during pretreatment
      periods or longer uptake periods, reduced phosphorus absorption and further
      reduced ATP synthesis. In these tissues it appears that oligomycin inhibits ATP
      production at the mitochondria, that ATP is the energy source for phosphorus
      uptake at the plasmalemma, and that a depletion in the ATP supply causes a
      reduced rate of uptake.

PMID- 16657155
TI  - Computer analysis of the leaf movements of pinto beans.
AB  - Computer analysis was used for the detection of rhythmic components and the
      estimation of period length in leaf movement records. The results of this study
      indicated that spectral analysis can be profitably used to determine rhythmic
      components in leaf movements.In Pinto bean plants (Phaseolus vulgaris L.) grown
      for 28 days under continuous light of 750 ft-c and at a constant temperature of
      28 degrees , there was only 1 highly significant rhythmic component in the leaf
      movements. The period of this rhythm was 27.3 hr. In plants grown at 20 degrees ,
      there were 2 highly significant rhythmic components: 1 of 13.8 hr and a much
      stronger 1 of 27.3 hr. At 15 degrees , the highly significant rhythmic components
      were also 27.3 and 13.8 hr in length but were of equal intensity. Random
      movements less than 9 hr in length became very pronounced at this temperature. At
      10 degrees , no significant rhythm was found in the leaf movements. At 5 degrees
      , the leaf movements ceased within 1 day.

PMID- 16657156
TI  - Growth Promotion in Pea Stem Sections. III. By Alkyl Nitriles, Alkyl Acetylenes
      and Insect Juvenile Hormones.
AB  - C(14), C(15), and C(16) alkyl nitriles, and C(16) and C(18) alkyl acetylenes at
      10 to 105 micromolar concentrations promote the growth of stem sections from red
      light-exposed seedlings of dwarf peas (Pisum sativum L. cv. Progress No. 9).
      Similar results were obtained with substances active as insect juvenile hormones,
      namely farnesol, the racemic ethyl ester of 1 of the natural hormones, and a
      "synthetic juvenile hormone" mixture, the latter 2 having as high an activity in
      the pea assay as any lipid reported previously. A sterically nearly identical
      compound, methyl-RS-10,11-epoxyfarnesoate, is a weak insect hormone and did not
      promote plant growth. Thus activity in peas and in insects is in some cases
      parallel. Other similarities and some differences are discussed. Peas appear to
      require molecules longer than 20A, while insect activity is maximal at that
      length. All active molecules are ineffective in promoting pea stem elongation by
      themselves, indole acetic acid must also be present. The lipid effect in plants
      and the juvenile hormone response in insects have much in common and the evidence
      suggests they could have a similar locus of action in a membrane controlling
      respiratory function.

PMID- 16657157
TI  - Presence of ADP-Glucose Pyrophosphorylase in Shrunken-2 and Brittle-2 Mutants of
      Maize Endosperm.
AB  - ADP-Glucose pyrophosphorylase activity has been detected in relatively low
      amounts in the embryos and endosperms of sh(2) and bt(2) mutant maize seeds. The
      total enzyme activities in sh(2) and bt(2) were about 12% and 17% respectively,
      of that found in starchy maize seeds (Dekalb 805). The ADP-glucose
      pyrophosphorylases from the starchy and mutant maize seeds were activated by 3
      phosphoglycerate. However, the extent of the activation of the sh(2) enzyme was
      not as great as that observed with the bt(2) and Dekalb 805 enzymes. The low
      levels of ADP-glucose pyrophosphorylase activity in the maize mutants correlate
      well with the low levels of starch found in the endosperm of these mutants.

PMID- 16657158
TI  - Cellular Localization of CO(2) Fixation and Translocation of Metabolites.
AB  - Leaves of maize (Zea mays L.) and sugar beet (Beta vulgaris L.) were enclosed in
      an illuminated chamber in air for 30 min after which time (14)CO(2) was released
      into the chamber. Two min after the (14)CO(2) was released, the leaves were
      removed from the chamber, and small sections were cut from them. The sections
      were put in small wire baskets and frozen in isopentane cooled by liquid
      nitrogen. Approximately 1.5 min elapsed from the removal of the leaf from the
      illuminated chamber until the tissue was frozen. The tissue was freeze-dried,
      embedded in paraffin and the cellular location of the isotopic activity was
      determined by radiography of leaf cross sections. Isotopic activity in maize
      leaves was localized in bundle sheath parenchyma. In contrast, the label in sugar
      beet leaves was generally distributed in the mesophyll cells. The bundle sheath
      cells in maize contain specialized chloroplasts which appear to have a unique
      capacity to incorporate CO(2). Translocation from leaves of maize was 3-fold as
      rapid as from sugar beet leaves in the same environment. Low light intensity did
      not alter the distribution pattern of fixed CO(2).

PMID- 16657159
TI  - Physiological Comparisons of Pith Callus With Crown-Gall and Genetic Tumors of
      Nicotiana glauca, N. langsdorffii, and N. glauca-langsdorffii Grown in Vitro. I.
      Tumor Induction and Proliferation.
AB  - Agrobacterium tumefaciens B-6 and T-37 strains, inoculated into Nicotiana glauca,
      N. langsdorffii, and their interspecific hybrid, which forms genetic
      (spontaneous) tumors as well, initiate amorphous tumors from the B-6 strain and
      organoid tumors (aberrant roots, stems, and buds) from the T-37 strain. In the
      hybrid, the critical point was to induce crown gall tumors at the site of
      wounding and not spontaneous genetic tumors. To succeed, this inoculation had to
      be made at a very early (5-6 leaf stage of development). It is observed that
      genetic organoid tumors readily formed at the nodes following flowering or leaf
      abscission. Furthermore, it was noted that genetic tumor derivatives are
      obtainable from hybrid pith callus or hybrid seedlings cultured in vitro.A marked
      difference in stem elongation was observed in hybrid tobacco plants inoculated
      with different strains of Agrobacterium tumefaciens or distilled water, and
      uninoculated controls. Inoculation of hybrid plants with the B-6-G2 avirulent
      strain of Agrobacterium tumefaciens stimulated stem elongation over controls, the
      T-37 inoculated stems were slightly stunted, and the B-6 inoculated stems were
      quite stunted and succumbed at an early age.

PMID- 16657160
TI  - Physiological Comparisons of Pith Callus With Crown-Gall and Genetic Tumors of
      Nicotiana glauca, N. langsdorffii, and N. glauca-langsdorffii Grown in Vitro. II.
      Nutritional Physiology.
AB  - Explants of genetic tumors, tumors initiated by Agrobacterium tumefaciens strains
      B-6 and T-37, and excised pith plugs from Nicotiana glauca, N. langsdorffii, and
      N. glauca-langsdorffii were cultured on Murashige and Skoog medium. All cultures,
      pith callus and tumors with the exception of N. langsdorffii pith grew on this
      medium. Addition of glutamine to the medium resulted in highly organoid growth in
      N. langsdorffii pith. In order to have material comparable to other pith
      cultures, N. langsdorffii was initiated on 2,4-dichlorophenoxyacetic acid medium,
      after which it grows on complete medium as amorphous pith callus. Except for the
      initiation of N. langsdorffii (and N. glauca) pith, the 2,4-dichlorophenoxyacetic
      acid medium, caused bleaching in cultures of T-37 induced tumors and death of B-6
      induced tumors. Tumor cultures, except for the seedling tumor, grew well on a
      minimal medium lacking kinetin, indoleacetic acid, vitamins, glycine, and
      inositol. Glycine was necessary only in the growth of N. langsdorffii pith
      callus. A tissue culture model is presented which permits comparison of the
      various tissue types.

PMID- 16657161
TI  - The effect of reduced water potential on soybean mitochondria.
AB  - The respiration of excised hypocotyls and of isolated hypocotyl mitochondria from
      soybean [Glycine max (L.) Merr., var. Wayne] was determined in various
      concentrations of sucrose and potassium chloride. Hypocotyl oxygen uptake
      declined with increasing solute concentration; no specific effects of either
      solute were apparent. Mitochondrial state III respiration was strongly inhibited
      as the solute concentrations were raised and there was in addition a specific
      inhibitory effect of the salt. State IV respiration, however, was unaffected by
      the presence of osmoticum. ADP/O ratios were also unaffected, except at high
      potassium chloride concentrations (470 mm). The primary effect of solutes was
      thus to limit the rate of substrate oxidation.Hydrostatic pressure did not
      reverse the decline in net phosphorylation accompanying reduced oxidation. It was
      inferred therefore that the inhibition was not due to lower water potential per
      se, but rather to some other effect of water or solute concentration.The effect
      of solutes on a mitochondrial enzyme, malate dehydrogenase, was also examined.
      Sucrose inhibited malate oxidation by both the mitochondria and the isolated
      enzyme in parallel, while potassium chloride was more inhibitory on the isolated
      enzyme. It was concluded that although the addition of solute lowers the water
      potential, the primary effects are exerted through specific effects of the solute
      on enzyme activity.

PMID- 16657162
TI  - Photosynthesis, Photorespiration and Respiration of Chloroplasts From
      Acetabularia mediterrania.
AB  - A chloroplast fraction isolated from Acetabularia mediterrania carries on
      photosynthesis at rates essentially equal to those of whole cells. Electron and
      phase contrast microscopy reveals that the chloroplasts are intact and well
      preserved. Preparations contain no identifiable peroxisomes, but some cytoplasmic
      and mitochondrial contamination is present. Photosynthesis and CO(2) production
      in light by chloroplast preparations are in many respects similar to that of bean
      leaves, although the measured rates are somewhat lower. Respiration and
      photosynthesis of chloroplast preparations and whole cells of Acetabularia is
      essentially similar except that cells have a strong dark-type respiration which
      continues in light and is CO(2) dependent, the substrate being mainly recent
      photosynthate. The data suggest that chloroplasts are the site of
      photorespiration.

PMID- 16657163
TI  - Ethylene, seed germination, and epinasty.
AB  - Ethylene activity in lettuce seed (Lactuca satina) germination and tomato
      (Lycopersicon esculentum) petiole epinasty has been characterized by using heat
      to inhibit ethylene synthesis. This procedure enabled a separation of the
      production of ethylene from the effect of ethylene. Ethylene was required in
      tomato petioles to produce the epinastic response and auxin was found to be
      active in producing epinasty through a stimulation of ethylene synthesis with the
      resulting ethylene being responsible for the epinasty. In the same manner, it was
      shown that gibberellic acid stimulated ethylene synthesis in lettuce seeds. The
      ethylene produced then in turn stimulated the seeds to germinate. It was
      hypothesized that ethylene was the intermediate which caused epinasty or seed
      germination. Auxin and gibberellin primarily induced their response by
      stimulating ethylene production.

PMID- 16657164
TI  - Water potential increase in sliced leaf tissue as a cause of error in vapor phase
      determinations of water potential.
AB  - Earlier reports that the water potential of sliced leaf tissue is higher than
      that of unsliced control tissue are confirmed. The effect is shown to increase as
      damage to the tissue due to slicing is increased. However, there is some evidence
      that increase in damage beyond a certain point causes water potentials to fall
      again towards the control value. The electrical resistance of washings from
      sliced leaf tissue increases with increase in the time interval between slicing
      and washing. Both the rise in water potential of sliced tissue and the rise in
      electrical resistance of washings are partially and reversibly inhibited by low
      temperature. These results suggest that the remaining intact cells actively
      accumulate solutes released from the cells cut open on slicing. The sap from the
      sliced cells is thereby diluted and flows passively into the intact cells. Since
      pressure potential changes more rapidly with cell volume than does osmotic
      potential, the net result is a rise in the total water potential of sliced
      tissue. It is concluded that this effect may cause spuriously high water
      potential values to be measured if excessively small pieces of leaf tissue are
      used. This is demonstrated with stacks of annuli cut from leaves.

PMID- 16657165
TI  - Effect of light intensity and plant size on rate of development of early boron
      deficiency symptoms in tomato root tips.
AB  - Young tomato plants (Lycopersicon esculentum Miller, cultivar Rutgers) grown in
      solution culture at 27 degrees at 2 light intensities with adequate boron (0.1
      mg/l) and treated with these 2 intensities in the absence of adequate boron
      developed root boron deficiency symptoms. The typical deficiency symptoms of
      decreased root elongation, increased depth of brown color and decreased RNA
      content of tips developed more rapidly at high than at low light intensity, and
      plant size influenced results. Plants supplied with adequate boron did not
      exhibit deficiency symptoms.

PMID- 16657166
TI  - Effect of lipids on chloride and sodium transport in bean and cotton plants.
AB  - This paper describes experiments on Cl transport into the roots, stem and leaves
      of bean plants, the roots of which have been exposed to lipids in the root
      solution. Monoand digalactose diglyceride strongly increased Cl transport into
      all plant parts, probably by transport of the glycolipids further into the plant.
      Phosphatidyl choline increased Cl absorption by the roots, but transport into the
      stem and leaves was not affected. This phospholipid was only absorbed by the root
      tissue. (32)P-glycerophosphoryl choline added to the root solution was readily
      transported and esterified as phospholipid in all plant parts. This chemical did
      increase Cl uptake by the roots but Cl accumulation in the leaves was reduced by
      as much as 40%. Phosphatidyl glycerol, phosphatidyl inositol, and sulfolipid
      increased Cl transport into roots, stem, and leaves, and a high mobility of (32)P
      phosphatidyl glycerol was demonstrated. Generally no significant effect of the
      above lipids on Na transport in beans and cotton was noted except that
      monogalactose diglyceride did increase Na transport in cotton.

PMID- 16657167
TI  - Effects of light quality on the circadian rhythm of leaf movement of a short-day
      plant.
AB  - Studies were made of the effects of blue, green, red and far-red (FR) light on
      the circadian rhythm of leaf movement of Coleus blumei x C. frederici, a short
      day plant. Under continuous illumination with blue light, there was a significant
      lengthening of the period of the rhythm to about 24.0 hr, as compared to 22.5 hr
      in continuous darkness. Under continuous red light, the period length was
      significantly shortened to 20.5 hr. Under continuous green or FR, the period
      length was not significantly different from the dark control. It was observed
      that under continuous FR illumination, the leaves tended to oscillate in a more
      downward position. Eight-hr red light signals were effective in advancing the
      phase of the rhythm as compared to a control under continuous green light. Blue
      light signals were effective in delaying the phase of the rhythm. FR light
      signals were ineffective in producing either delay or advance phase shifts. Far
      red light did not reverse the effects of either red or blue light signals. On the
      basis of these results it is suggested, that pigments which absorb blue or red
      light, rather than phytochrome, mediate the effect of light on the circadian
      rhythm of leaf movement.

PMID- 16657168
TI  - The Use of Nucleoside Phosphotransferase and (P) p-Nitrophenyl Phosphate in the
      Determination of the 5'-Linked Termini of Ribosomal RNA.
AB  - A method for the identification of the 5'-linked termini of ribosomal RNA is
      described. The method involves the phosphorylation of the nucleosides released
      from the 5'-linked termini after hydrolysis of the ribonucleic acid chain with
      alkali. The radioactive 5'-nucleotide derivatives are formed by a nucleoside
      phosphotransferase mediated phosphoryl transfer from ((32)P) p-nitrophenyl
      phosphate to the nucleosides. The sensitivity of the method allows the use of
      small amounts of ribosomal RNA.Phosphorylation of the terminal nucleosides
      released from unfractionated cauliflower ribosomal RNA yielded radioactive
      adenylic acid and uridylic acid primarily, with the amount of adenylic acid being
      approximately twice that of uridylic acid.

PMID- 16657169
TI  - Calcium uptake by excised maize roots and interactions with alkali cations.
AB  - Ca(2+) uptake was studied in short-term experiments using 5-day-old excised maize
      roots. This tissue readily absorbs Ca(2+), and inhibition by dinitrophenol and
      low temperature shows that the process is metabolically mediated. The uptake of
      Ca(2+), like that of other cations, is influenced by the counter ion, the pH and
      concentration of the ambient solution, and the presence of other cations. The
      rate of uptake from various salts decreases in the following order: NO(3) (-) >
      Cl(-) = Br(-) > SO(4) (2-). K(+) and H(+) greatly interfere with Ca(2+)
      absorption, while Li(+) and Na(+) have only slight effects.

PMID- 16657170
TI  - Chloroplast Ultrastructure in Mutant Strains of Chlamydomonas reinhardi Lacking
      Components of the Photosynthetic Apparatus.
AB  - The fine structure of the chloroplast of wild-type and 9 photosynthetic mutant
      strains of Chlamydomonas reinhardi is described. The chloroplast phenotypes of
      the mutant strains are clearly distinct from the wild type in all but 2 cases.
      Moreover, strains with similar photosynthetic disabilities have structurally
      similar chloroplasts. These differences are apparently not the result of altered
      chlorophyll content, nor of photosynthetic inactivity. It is therefore proposed
      that the structural alterations are in some way related to the mutant strains'
      inability to synthesize active components of the photosynthetic electron
      transport chain.

PMID- 16657171
TI  - Long-lived Intermediates in Phytochrome Transformation I: In Vitro Studies.
AB  - Irradiation of phytochrome solutions with a high-intensity mixed red and far red
      light source causes measurable absorbancy increases at 543 nm. Evidence is
      presented that these absorbancy increases are caused by accumulation of
      intermediates on the P(R) to P(FR) pathway with relatively slow thermal decay
      constants. Kinetic analysis of the decay signals is consistent with the
      interpretation that the signals represent simultaneous independent and parallel
      decay of 2 species by first order kinetics to P(FR). If actinic light intensity
      is kept constant and exposure time changed, the relative amounts of the 2
      components change, with proportionately more of the rapidly decaying species
      present following short exposure times. If the amount of the intermediates is
      decreased by decreasing actinic light intensity at constant exposure time,
      however, the relative amounts of the 2 remain constant. The Q(10) for
      intermediate decay following illumination is approximately 2.0, while that for
      complete phototransformation of the pigment in either direction is very close to
      1.0. Incomplete transformation of P(R) to P(FR), caused by overlapping absorption
      of the 2 forms, is shown by the presence of intermediates (indicating cycling of
      the pigment) in continuous red light. Such intermediates do not appear in
      continuous far red, indicating a rate of pigment cycling below detection by the
      available instrumentation.

PMID- 16657172
TI  - Long-lived Intermediates in Phytochrome Transformation II: In Vitro and In Vivo
      Studies.
AB  - Conditions of illumination which cause phytochrome to cycle rapidly from P(R) to
      P(FR) and back lead to the accumulation in vivo of detectable amounts of long
      lived intermediates on the P(R) to P(FR) pathway in oat coleoptile tissue. They
      appear to decay independently and in parallel to P(FR). Their behavior under
      different intensities of illumination and exposure time suggests that they are
      homologous with 2 similar intermediates previously observed in vitro. Available
      evidence favoring this suggestion is discussed. Equivalent illumination
      apparently causes far higher steady state levels of absorption by intermediates
      in vivo than in vitro, suggestion that native phytochrome is in a different
      physical state in the cell than it is in solution. A difference spectrum for the
      intermediates in vitro between 365 and 580 nm is presented. It has a maximum at
      380 nm, a minimum at 418 nm, and crossover points at 398 and 485 nm. Glycerol in
      the phytochrome sample enhances the signal without otherwise changing the
      spectrum in any way. The difference spectrum represents the difference in
      absorption between the combined intermediates and P(FR).

PMID- 16657173
TI  - Radial transport of ions in roots.
AB  - Measurements were made of the relative amounts of (86)Rb, (36)Cl, and (32)P
      accumulated in the cortex and stele of intact roots of corn (Zea mays), either
      detached or attached to their shoots. Both 4- and 7-day-old roots accumulated as
      much or more (86)Rb in the stele as in the cortex. In experiments with (36)Cl,
      cortex and stele accumulated the same amount, except for 4-day-old and 7-day-old
      attached roots, in which the cortex contained more (36)Cl than the stele after 23
      hr. An additional study of (32)P uptake showed greater accumulation in the cortex
      than the stele for a short period of time, but as much in the stele as in the
      cortex after 8 to 24 hr. Transport of (86)Rb, (36)Cl, and (32)P into the xylem
      exudate increased with increasing accumulation of these ions in stele and cortex
      of the root. These experiments show no consistent difference between cortex and
      stele of intact corn roots with respect to their ability to accumulate several
      kinds of ions.

PMID- 16657174
TI  - Mechanism of the Seismonastic Reaction in Mimosa pudica.
AB  - The efflux of K(+) from the pulvinar cells of Mimosa pudica was shown to increase
      substantially during the seismonastic reaction. This result is shown to indicate
      a decrease in sigma (reflection coefficient) of pulvinar cell membrane for
      potassium salts which could account for the pulvinar cell turgor decrease during
      the seismonastic reaction.Membrane potentials and concentrations of Ca(2+), K(+),
      Cl(-), S, and P were measured in the top and bottom halves of pulvini. Pulvinar
      cells showed a large negative membrane potential, cell vacuole relative to
      external solution, but no significant difference in membrane potential could be
      detected between upper and lower pulvinar cells. A large difference in K(+) and
      Cl(-) concentration between top and bottom pulvinar halves was evident in
      reactive pulvini but not in unreactive pulvini. The effect of K(+) concentration
      on plant growth and leaf reactivity was also investigated.

PMID- 16657175
TI  - Iron accumulation, root peroxidase activity, and varietal interactions in soybean
      genotypes that differ in iron nutrition.
AB  - Four soybean genotypes (Glycine max L. Merrill) differing in their ability to
      accumulate iron were studied: the efficient genotypes Hawkeye (HA) and A62-9 (E
      9) and the inefficient genotypes PI-54619-5-1 (PI) and A62-10 (I-10).The
      distribution of iron in the tissues of plants grown in a growth chamber in
      nutrient solutions containing various levels of iron was determined. A greater
      amount of iron was associated with the roots of inefficient plants than with
      roots of efficient plants, indicating a slower rate of iron translocation in the
      former. After determination of the amount of iron in the shoots at low levels of
      nutrient iron, the ability of the several genotypes to accumulate iron was rated
      HA> E-9> I-10>/= PI. At the highest level of nutrient iron the rated efficiencies
      were E-9> HA> I-10> PI. Accumulation of iron in the primary leaves provided an
      excellent indication of whole-plant iron accumulation. A reduction in
      accumulation of iron by efficient plants occurred when the plants were grown
      together in the same solution as inefficient ones.

PMID- 16657176
TI  - Inhibition of photosynthesis by oxygen in isolated spinach chloroplasts.
AB  - The inhibition of photosynthetic CO(2) fixation by O(2), commonly referred to as
      the Warburg effect, was examined in isolated intact spinach (Spinacia oleracea)
      chloroplasts. The major characteristics of this effect in isolated chloroplasts
      are rapid reversibility when O(2) is replaced by N(2), an increased inhibition by
      O(2) at low concentrations of CO(2) and a decreased effect of O(2) with increased
      concentrations of CO(2).Both the DPN- and TPN-linked glyceraldehyde 3-phosphate
      dehydrogenases but not aldolase were inhibited by O(2). The photoreduction of TPN
      measured in fragmented chloroplast preparations was similar in N(2) and O(2) down
      to a concentration of 5 micromolar TPN. The effect of 100% O(2) on (14)CO(2)
      assimilation was overcome completely by fructose 1,6-diphosphate and by ribose 5
      phosphate but not by ascorbate, cysteine, dithiothreitol and reduced lipoate.
      Glycolate became the major photosynthetic product at high partial pressures of
      O(2) or at low CO(2) concentrations. It is concluded that O(2) depresses
      photosynthesis primarily by causing a shift of a major portion of the total
      carbon into glycolate and impairing the functioning of the photosynthetic carbon
      reduction cycle. The mechanism whereby O(2) alters the flow of carbon into
      glycolate remains unknown.

PMID- 16657177
TI  - Calibration of Infra-red CO(2) Gas Analyzers.
AB  - Precision gas mixing pumps produce CO(2) gas mixtures for the calibration of
      infra-red CO(2) gas analyzers equivalent in accuracy to the standard CO(2) gas
      mixtures (+/- 1%) supplied by the National Bureau of Standards, Washington, D.
      C.The calibration of infra-red gas analyzers by the pressure difference method
      and by concentration differences did not agree. A factor of 0.709 was necessary
      to correct the pressure difference method for the effects of pressure broadening
      with our analyzer.

PMID- 16657178
TI  - Control of apple ripening by succinic Acid 2,2-dimethyl hydrazide, 2
      chloroethyltrimethylammonium chloride, and ethylene.
AB  - Ripening of ;Tydeman's Early' apples (Malus sylvestris L.) assessed by the
      occurrence of the respiratory climacteric was delayed by succinic acid 2,2
      dimethyl hydrazide (B-9) but not by 2-chloroethyltrimethylammonium chloride
      (CCC), each applied 14 days after bloom. B-9 also inhibited ethylene production
      by fruits exhibiting the climacteric rise. Inhibition of the climacteric by B-9
      was overcome by exogenous ethylene, but the latter treatment failed to completely
      reverse the B-9 inhibition of endogenous ethylene production.In apple fruitlets
      harvested within 6 weeks of bloom, ethylene stimulated respiration but did not
      initiate a climacteric respiratory pattern, did not induce a color change, and
      did not give rise to any measurable increase in endogenous ethylene production.
      However, all of these changes did occur in more mature fruit. These data suggest
      that apples have 2 physiological stages with regard to their reaction to
      exogenous ethylene.

PMID- 16657179
TI  - Involvement of Aminoacyl-tRNA Transfer Factors in Polyphenylalanine Synthesis by
      Rice Embryo Ribosomes.
AB  - Two distinct heat labile factors (I and II) were found to be required for the in
      vitro synthesis of polyphenylalanine by rice ribosomes (Oryza sativa var.
      Bluebonnct) and polyuridylic acid. These factors were present in both the crude
      supernatant and on crude ribosomes. Factor I was removed from the crude ribosomes
      by [ill] (0.6%), while factor II was eliminated from deoxycholate washed
      ribosomes by a 0.5 m KCl wash.Factor I was purified from crude supernatant by
      calcium phosphate absorption and elution followed by polyacrylamide gel
      electrophoresis. Purified factor I was able to substitute for crude supernatant
      in supporting polyphenylalanine synthesis with deoxycholate washed ribosomes.The
      supernatant fraction from a KCl wash of deoxycholate ribosomes was found to
      contain factor II but no factor I activity. Factor II activity was also present
      in the calcium elutant fraction prepared from crude supernatant. Both factors I
      and II were required in order to substitute for crude supernatant in supporting
      polyphenylalanine synthesis with KCl washed ribosomes.The optimum Mg
      concentration for polyphenylalanine synthesis with d-oxycholate ribosomes was 4.5
      mm with crude supernatant, and 6.5 mm with purified factor I. However, with KCl
      ribosomes supplemented with factors I and II, the optimum was 8.5 mm.Analytical
      ultracentrifugation Schlieren patterns indicated that KCl washed ribosomes
      contained a significant quantity of ribosomal subunits.

PMID- 16657180
TI  - Abscission: quantitative measurement with a recording abscissor.
AB  - The construction, operation, and effectiveness of an abscission measuring
      instrument called an abscissor is described. The device measured the force
      required for a spring-opposed plunger to shear abscission zone explants and was
      capable of automatically recording break strength data. Examples of data obtained
      with the abscissor are presented to demonstrate its capability of rapidly
      measuring significant changes in explant break strength.

PMID- 16657181
TI  - Abscission: role of abscisic Acid.
AB  - The effect of abscisic acid on cotton (Gossypium hirsutum L. cv. Acala 4-42) and
      bean (Phaseolus vulgaris L. cv. Red Kidney) explants was 2-fold. It increased
      ethylene production from the explants, which was found to account for some of its
      ability to accelerate abscission. Absci is acid also increased the activity of
      cellulase. Increased synthesis of cellulase was not du to an increase in aging of
      the explants but rather was an effect of abscisic acid on the processes that lead
      to cellulase synthesis or activity.

PMID- 16657182
TI  - Evidence for an Inactivating System of Nitrate Reductase in Hordeum vulgare L.
      during Darkness That Requires Protein Synthesis.
AB  - The disappearance of nitrate reductase activity in leaves of Hordeum vulgare L.
      during darkness was inhibited by cycloheximide, actinomycin D, and low
      temperature. Thus, protein synthesis was probably required for the disappearance
      of nitrate reductase in the dark. Since chloramphenicol did not affect the rate
      of loss of activity, the degradation or inactivation apparently required protein
      synthesis by the cytoplasmic ribosomal system. Consistent with this observation,
      nitrate reductase is also reportedly located in the cytoplasm. Thus, the amount
      of nitrate reductase activity present in leaves of barley may be controlled by a
      balance between activating and inactivating systems.

PMID- 16657183
TI  - Transport and metabolism of indole-3-acetic Acid in coleus petiole segments of
      increasing age.
AB  - Transport and metabolism of IAA-1-(14)C in Coleus blumei Benth. was studied by
      means of a combination of liquid scintillation counting, autoradiography and thin
      layer chromatography. Transport of IAA in petiole segments of increasing age (No.
      2-8) was strictly polar in a basipetal direction. No acropetal movement occurred
      in either young or old tissues. The greatest amount, expressed as a percentage of
      the radioactivity lost from the donor block, was found in basal receivers on
      petiole number 2. There was gradually less transport in older segments. The
      recovery as a percentage of the radioactivity not accounted for by donor and
      receiver blocks, measured by counting the radioactivity in an acetonitrile
      extract of petiole segments, was low: 25 to 50%. In this acetonitrile-soluble
      fraction evidence for different radioactive compounds was found, depending on the
      age of the tissue. A possible relationship between the amounts of auxin
      transported in the tissue and its corresponding metabolism is discussed.

PMID- 16657184
TI  - Studies on Auxin Protectors. VII. Association of Auxin Protectors With Crown Gall
      Development in Sunflower Stems.
AB  - Mature sunflower internodes contain only very low concentrations of auxin
      protectors. Wounding such internodes results in a temporary increase of protector
      substances. Inoculating the wounds with a virulent strain of Agrobacterium
      tumefaciens Conn results in a dramatic rise in protector substances, particularly
      the very high molecular weight protector "A", which continues as the tumors
      develop. The levels attained in tumor tissue are comparable to those normally
      encountered in meristematic tissue. Since the auxin protectors are antioxidants
      which inhibit the peroxidase-catalyzed oxidation of IAA, and in view of the
      findings by other workers that the meristematic tissues are maintained in a
      relatively reduced state, the presence of such large quantities of protector
      substances in the tumor tissue could explain the physiological and morphological
      similarity of tumor tissue to young meristematic tissue.

PMID- 16657185
TI  - A Quantitative Estimation of Alkali-labile Indole-3-Acetic Acid Compounds in
      Dormant and Germinating Maize Kernels.
AB  - An estimate has been made of the quantities of alkali-labile esters of
      indoleacetic acid (IAA) in kernels of sweet corn (Zea mays). The amount is
      between 70 to 90 mg of IAA per kilogram of dry kernels. About one-half of the IAA
      is present as high molecular weight esters and the remaining one-half as esters
      of myo-inositol. Free IAA, which may have existed in the kernels, or may have
      resulted from ester hydrolysis during isolation or storage, amounts to between 1
      to 10% of the esterified IAA. Five newly observed low molecular weight
      indoleacetyl compounds are described and their chromatographic behavior reported.
      The total IAA content of corn kernels and intact seedlings decreases during
      germination, declining to about 10% of the original content during 96 hr of
      germination. Difficulties in obtaining quantitative results and the possible
      physiological significance of these results is discussed.

PMID- 16657186
TI  - Magnesium uptake by soybeans.
AB  - Magnesium contents of soybean (Glycine max) roots increase and the K and Ca
      contents decrease with increased MgCl(2) concentrations in ambient solutions. The
      Mg uptake is inhibited when both Ca and K are present in the solution, but not by
      K or Ca alone. Chloride uptake, which is very low from the MgCl(2) solution, is
      greatly enhanced by the presence of K. The selectivity against Mg imparted by K +
      Ca appears to be at an external barrier for cation uptake as shown by its
      dependence on the presence of Ca in the external solution. The Ca content of
      roots is influenced only slightly by changes in external Ca concentrations from
      10(-4) to 10(-2)m, but that of shoots is greatly enhanced as the Ca concentration
      is increased or the K concentration is decreased. These effects on Ca contents
      are explained as arising from transport to the shoot without involvement of
      vacuoles of root cells.

PMID- 16657187
TI  - Synthesis and secretion of hydroxyproline containing macromolecules in carrots.
      I. Kinetic analysis.
AB  - When disks of carrot (Daucus carota) phloem parenchyma are incubated for 6 days
      there is a 10-fold increase in cell wall hydroxyproline due to the synthesis and
      secretion of hydroxyproline-containing macromolecules. The synthesis of these
      molecules and their secretion are demonstrated by measuring the kinetics of
      incorporation and of chase of (14)C-proline and hydroxyproline in different
      fractions of the cytoplasm and the cell wall. The hydroxyproline-containing
      molecules which are secreted are associated with the membranous organelles of the
      cytoplasm. They can be fractionated into trichloroacetic acid-soluble and
      trichloroacetic acid-precipitated fractions. The properties of the
      trichloroacetic acid-soluble fraction associated with the membranous organelles
      are consistent with its role as a cell wall precursor.

PMID- 16657188
TI  - Ethylene evolution stimulated by chilling in citrus and persea sp.

PMID- 16657189
TI  - The effect of tungstate on nitrate assimilation in higher plant tissues.

PMID- 16657190
TI  - Regulation of the Onset of Dormancy in Tubers of Begonia evansiana.

PMID- 16657191
TI  - Ethylene evolution from 2-chloroethylphosphonic Acid.

PMID- 16657192
TI  - Removal of zinc from phosphate solutions by anion-exchange.

PMID- 16657193
TI  - Blockage by gibberellic Acid of phytochrome effects on growth, auxin responses,
      and flavonoid synthesis in etiolated pea internodes.
AB  - Red light inhibits the growth of etiolated pea internodes, causes a shift toward
      higher indoleacetic acid (IAA) concentrations in the IAA dose-response curve of
      excised sections, and promotes the synthesis in intact internodes of kaempferol-3
      triglucoside. Gibberellic acid (GA(3)) prevents all 3 effects, the first effect
      substantially and the last 2 completely. This suggests GA(3) blockage of an early
      or basic event initiated by the active form of phytochrome. The red light-induced
      shift in the IAA dose-response curve of excised sections is consistent with a
      light-induced increase in the activity of an IAA destruction system, since the
      magnitude of the red light inhibition varied with IAA concentration. The red
      light and GA(3) effects on growth and on flavonoid synthesis are consistent with
      the view that phytochrome may control growth by regulating the synthesis of
      phenolic compounds which act as cofactors in an IAA-oxidase system. GA(3)
      reversal of the red light-induced shift in the IAA dose-response curve involves
      both growth promotion and inhibition by GA(3) at different IAA concentrations and
      this, together with the GA(3) reversal of light-induced flavonoid synthesis,
      supports the suggested regulatory role of phenolic compounds in growth.

PMID- 16657194
TI  - beta-Alanine as an Ethylene Precursor. Investigations Towards Preparation, and
      Properties, of a Soluble Enzyme System From a Subcellular Particulate Fraction of
      Bean Cotyledons.
AB  - A method is described for the preparation, from a subcellular particulate
      fraction of wax bean cotyledons, of a soluble enzyme system that is capable of
      converting beta-alanine to ethylene. In the presence of ATP, CoA, thiamine
      pyrophosphate, MgSO(4), and pyridoxal phosphate, ethylene production is maximum
      at a 0.5 mm concentration of beta-alanine. The system exhibits a pH optimum at
      7.0 but when the pH is raised above 8, evolution of the volatile again increases
      and continues to do so up to pH 12. The enzyme system is stimulated by either
      NADPH or NADH; the concentration of NADPH necessary to obtain maximum activity is
      twice that of NADH. The requirement for a reducing agent is in agreement with the
      proposal that malonate semialdehyde, formed by an aminotransferase reaction from
      beta-alanine, is reduced to beta-hydroxypropionate. Both malonate semialdehyde
      and beta-hydroxypropionate are better stimulators of production of the volatile
      in the soluble system than is beta-alanine, and beta-hydroxypropionate is a
      better stimulator than malonate semialdehyde. This system is also able to
      incorporate tritium from tritiated water into ethylene; this supports the
      proposal that ethylene is formed by the decarboxylation of acrylate, the latter
      being formed from beta-hydroxypropionate.Experiments with both cold and labeled
      malonate suggest that this compound stimulates ethylene production by acting as
      an end product inhibitor that prevents the loss of malonate semialdehyde from the
      pathway. Malonate does not appear to serve as a precursor.Addition of cytoplasmic
      enzymes to the ;soluble system' (prepared from particulate enzymes) results in a
      considerable boost in ethylene production, but the specific activity (mmu1 / mg
      protein) is lowered from that of the particulate enzymes alone.

PMID- 16657195
TI  - A survey of the sequence of some effects of gibberellic Acid in the metabolism of
      cereal grains.
AB  - The sequence in which a variety of enzymes and metabolites are affected by
      gibberellic acid after application of the hormone to aleurone layers of half
      seeds of barley (Hordeum vulgare var. Betzes) and half seeds of wheat (Triticum
      aestivum var. Gensee) was investigated. With barley aleurone layers the first
      hormonal effect observed was the increased secretion of soluble carbohydrate,
      some of which appears to be a glucan containing some beta-1,3 linkages. This was
      followed by increased oxygen consumption and increased secretion of ATPase,
      GTPase, phytase, phosphomonoesterase, phosphodiesterase, inorganic phosphate,
      carbohydrates other than amylase, peroxidase and amylase. Similar sequential
      effects were seen in wheat half seeds. Increased activity of alcohol
      dehydrogenase in barley seeds was elicited by the hormone but there was no effect
      on glucose-6-phosphate isomerase.

PMID- 16657196
TI  - Adaptation of barley roots to low oxygen supply and its relation to potassium and
      sodium uptake.
AB  - The uptake of Na(+) and K(+) by barley seedlings grown on aerated or non-aerated
      solutions was studied. Plants growing in culture solution took up K(+) with high
      selectivity whether the solution was aerated or not. Roots of plants grown on
      aerated CaSO(4) and transferred to a solution of KCl and NaCl had a lower
      preference for K(+) than roots of plants grown on non-aerated CaSO(4). Both kinds
      of low-salt roots were much less able to discriminate between K(+) and Na(+) than
      high-salt roots grown on a culture solution. The different levels of K(+)
      selectivity are suggested to be related to H(+) release from the tissue.

PMID- 16657197
TI  - Influence of age and sulfur metabolism on ATP sulfurylase activity in the soybean
      and a survey of selected species.
AB  - ATP sulfurylase activity varied greatly among different leaves on the soybean
      plant [Glycine max (L.) Meer.], and high levels of activity did not appear in the
      leaves until the seedlings were about 3 weeks old. In general, leaves from the
      top of the plant had a higher activity than leaves from the bottom of the plant.
      A much greater activity was found in soybean leaves than in soybean roots. The
      absence of sulfate in the nutrient solution resulted in higher enzyme activity in
      leaves from young plants and in lower activity in leaves from older plants. Over
      the growing season, however, ATP sulfurylase activity appeared to be related to
      sulfur content of the leaf. Several other plant species also had measurable
      levels of ATP sulfurylase.

PMID- 16657198
TI  - Influence of Benzyladenine, Leaf Darkening, and Ringing on Movement of C-labeled
      Assimilates Into Expanded Leaves of Vitis vinifera L.
AB  - Leaves of Vitis vinifera L., nearly fully expanded, imported only trace amounts
      of (14)C following assimilation of (14)CO(2) by a lower leaf on the same shoot,
      but benzyladenine (BA) application at 4.4 x 10(-3)m caused a marked increase in
      the movement of (14)C into these leaves. Older leaves near the shoot base were
      less responsive; BA treatment alone had little effect on import of labeled
      assimilates from adjacent leaves but when the BA-treated leaves were darkened
      there was an increased import of labeled materials. When these 2 treatments were
      combined and applied to leaves on shoots with ringed bases, relatively high
      levels of radioactivity were detected in the BA-treated leaves but under these
      conditions darkening, without the application of BA, also resulted in an
      increased import of (14)C. Accumulation of imported (14)C was found to be
      restricted to the area of the leaf blade treated with BA. Separation of labeled
      compounds in ethanol extracts of treated leaves showed a lower percentage of
      radioactivity present in the sugar fraction from BA-treated leaves and an
      increased percentage present in the amino acid fraction.

PMID- 16657199
TI  - Regulation of sulfate uptake by amino acids in cultured tobacco cells.
AB  - The sulfur requirements of tobacco (Nicotiana tabacum L. var. Xanthi) XD cells
      grown in chemically defined liquid media can be satisfied by sulfate,
      thiosulfate, l-cyst(e)ine, l-methionine or glutathione, and somewhat less
      effectively by d-cyst (e) ine, d-methionine or dl-homocyst (e)ine. Sulfate uptake
      is inhibited after a 2 hr lag by l-cyst (e)ine, l-methionine, l-homocyst(e)ine or
      l-isoleucine, but not by any of the other protein amino acids, nor by d
      cyst(e)ine. l-cyst(e)ine is neither a competitive nor a non-competitive inhibitor
      of sulfate uptake. Its action most closely resembles apparent uncompetitive
      inhibition. Inhibition of sulfate uptake by l-cyst(e)ine can be partially
      prevented by equimolar l-arginine, l-lysine, l-leucine, l-phenylalanine, l
      tyrosine or l-tryptophan, but is little affected by any of the other protein
      amino acids. The effective amino acids are apparent competitive inhibitors of l
      cyst(e)ine uptake after a 2 hr lag. Inhibition of sulfate uptake by l-methionine
      cannot be prevented, nor can uptake of l-methionine be inhibited by any single
      protein amino acid. The results suggest the occurrence of negative feedback
      control of sulfate assimilation by the end products, the sulfur amino acids, in
      cultured tobacco cells.

PMID- 16657200
TI  - Effects of univalent cations on the activity of particulate starch synthetase.
AB  - An investigation was made to determine the univalent cation requirements of
      starch synthetase from a variety of plant species of economic importance. The
      particulate enzyme from sweet corn was shown to have an absolute requirement for
      potassium, with the optimum activation occurring at 0.05 M KCl. Rubidium, cesium,
      and ammonium were 80% as effective as potassium while sodium and lithium were
      respectively 21% and 8% as effective as potassium. The K(A) for potassium was
      determined to be 6 mM. In the case of the particulate starch synthetase from
      wheat, bush beans, field corn, soybeans, peas, or potatoes, considerable
      stimulation of enzyme activity was obtained by the addition of potassium to the
      reaction mixture. In these studies, low enzyme activity was observed in the
      absence of added potassium, but the content of endogenous univalent cations in
      the reactions may be sufficient to account for the activities observed. Anions of
      various types had no effect on starch synthetase activity. Divalent cations
      produced slight activation in the presence or absence of potassium. All efforts
      to show a potassium requirement for glycogen synthetase from rat liver have been
      negative.

PMID- 16657201
TI  - Uptake of 3-o-Methylglucose by Healthy and Hypomyces-infected Squash Hypocotyls.
AB  - Rates of uptake of 3-o-methylglucose (MeG) by squash (Cucurbita maxima) hypocotyl
      sections from above lesions caused by Hypomyces solani f. sp. cucurbitae, race 1,
      are 2-fold greater than uptake by comparable tissues from healthy plants. Kinetic
      analyses indicate (i) that a single (constitutive) carrier system, with a
      Michaelis constant (Km) of 25 to 30 mm, mediates the transport of MeG into
      healthy hypocotyl cells and (ii) that an additional (inducible) system with a
      much lower Km (ca. 2 mm) is present in diseased hypocotyls. In both systems MeG
      uptake is inhibited competitively by glucose. The inducible transport system (s)
      in diseased tissues has a higher temperature coefficient, greater sensitivity to
      metabolic inhibitors and larger accumulation capacity than the one in healthy
      plants. While the nature of the constitutive system is ambiguous, the inducible
      carrier mechanism is a typical active transport system. These results indicate
      that increased rates of uptake and accumulation of metabolites by diseased
      tissues can be caused by new transport systems.

PMID- 16657202
TI  - Pear bud metabolism: seasonal changes in glucose utilization.
AB  - Utilization of glucose, uracil and valine by flower and leaf buds of seedling
      pear trees (Pyrus calleryana Decne.) from the time of flower bud initiation to
      flowering was investigated. A very high rate of glucose utilization through the
      pentose phosphate pathway was observed throughout the development of buds. There
      was no difference in the type of glucose metabolism between flower and leaf buds
      except immediately before flowering, when the metabolism in flower buds was
      shifted toward the glycolytic pathway. Such a shift did not occur in leaf buds.
      The incorporation of uracil and valine into the nucleic acid and protein fraction
      of buds, respectively, was high throughout bud development, perhaps indicating a
      high rate of turnover in the resting buds. Incorporation of both compounds
      decreased when buds started to expand prior to flowering.

PMID- 16657203
TI  - Movement and metabolism of kinetin-C and of adenine-C in coleus petiole segments
      of increasing age.
AB  - To see if polar movement was typical of growth-regulators other than auxins, the
      movement of adenine-8-(14)C and of kinetin-8-(14)C was studied in segments cut
      from petioles of increasing age. No polarity was found. In time-course
      experiments lasting 24 hr, kinetin showed a progressive increase of radioactivity
      in receiver blocks, while adenine showed a maximum at 8 hr with a decline
      thereafter. More kinetin moved through older segments than through younger ones.
      There was no difference in net loss as far as the position of the donor block is
      concerned. However, the loss of radioactivity from adenine donor blocks was much
      higher than the loss of radioactivity from kinetin donor blocks.The radioactivity
      in receiver blocks after 24 hr treatment with kinetin-(14)C was still with
      kinetin, judging by location on chromatograms. By the same criterion, adenine and
      a smaller amount of some other compound were in receiver blocks after a 6 hr
      transport with adenine-(14)C in the donors. By contrast, more zones of
      radioactivity were extracted from petiole segments to which kinetin or adenine
      had been added. For both purine derivatives the original compound represented no
      more than 20% of the total radioactivity extracted from the tissue after a
      transport period of 24 hr.

PMID- 16657204
TI  - Photosynthetic Studies on a Pea-mutant Deficient in Chlorophyll.
AB  - A chlorophyll-deficient mutant of pea (Pisum sativum) was found as a spontaneous
      mutation of the variety Greenfeast. Total chlorophyll of the mutant leaves was
      about one-half that of normal pea leaves per mg dry weight, and the ratio of chl
      a:chl b ranged from 10 to 18, compared with 3 for normal pea. In each generation
      the mutant plants gave rise to normal and mutant plants and lethal plants with
      yellow leaves.For a normal pea plant, CO(2) uptake was saturated at about 60,000
      lux, whereas with mutant leaves, the rate of CO(2) uptake was still increasing at
      113,000 lux. At 113,000 lux the mutant and normal leaves showed similar rates of
      CO(2) fixation per unit area of leaf surface, but on a chlorophyll basis the
      mutant leaves were twice as active. Hill reaction measurements on isolated
      chloroplasts also showed that the mutant chloroplasts were saturated at higher
      intensities than the normal, and that the activity of the mutant was at least
      double that of the normal on a chlorophyll basis.It is suggested that the
      photosynthetic units of the mutant chloroplasts contain about half the number of
      chlorophyll molecules as compared to the normal photosynthetic units.Electron
      microscopy of leaf sections of normal and mutant leaves showed that the mutant
      chloroplasts contain fewer lamellae per chloroplast and fewer lamellae per
      granum. The lethal chloroplasts, which were virtually devoid of chlorophyll, were
      characterized by an absence of grana.

PMID- 16657205
TI  - Effect of Vanadium on Growth, Chemical Composition, and Metabolic Processes of
      Mature Sugar Beet (Beta vulgaris L.) Plants.
AB  - As measured 7, 14, and 21 days after the application of 10(-2) M vanadyl sulfate
      solution to the foliage of 4.5-month-old sugar beet plants, significantly less
      growth of the leaves and an increase in the sucrose content of the storage root
      resulted. Accompanying these alterations were a higher rate of carbon dioxide
      fixation, a lower rate of respiration, and a decreased rate of nitrate reductase,
      glutamic-pyruvic transaminase, phosphatase, and invertase activity. The enzymes
      of sucrose synthesis, sucrose synthetase, sucrose phosphate synthetase and
      uridine diphosphate glucose-pyrophosphorylase were stimulated. The content of
      reducing sugar, nitrite N, amino acids and protein was less, and that of nitrate
      N was greater in the vanadium-treated plants. In the majority of cases the
      greatest magnitude of change occurred during the first 7 days following
      treatment. The changes in growth and chemical composition are believed to be
      closely related to the stimulation or inhibition of the various enzymes by
      vanadyl sulfate.

PMID- 16657206
TI  - Carbon Dioxide Exchanges in Leaves. I. Discrimination Between CO(2) and CO(2) in
      Photosynthesis.
AB  - In order to measure CO(2) exchange reactions by leaves using isotopes of CO(2),
      it is necessary to know precisely the discrimination against (14)CO(2) by leaves.
      Earlier determinations of discrimination are at variance, and may be inaccurate
      because of assumptions made about the rate of photorespiration. Maize leaves
      evolve little or no CO(2) in light, and so provide suitable material for this
      measurement. Discrimination against (14)CO(2) in photosynthesis by maize leaves
      is almost precisely the same as in CO(2) absorption by NaOH solution, amounting
      to 2.1 and 2.0% respectively. The agreement between these values and their close
      approximation to the relative rates of diffusion of (12)CO(2) and (14)CO(2),
      calculated from Graham's law, shows that diffusion into the leaf is primarily
      responsible for discrimination against (14)CO(2) in photosynthesis.

PMID- 16657207
TI  - Precursors of ethylene.

PMID- 16657208
TI  - Direct determination of potassium ion accumulation in guard cells in relation to
      stomatal opening in light.

PMID- 16657209
TI  - A site with an affinity for heavy metals on the thylakoid membranes of
      chloroplasts.

PMID- 16657210
TI  - Apparent changes in rate of kaurene biosynthesis during the development of pea
      seeds.

PMID- 16657211
TI  - Oxygen Requirement for Ethane Production In Vitro by Phaseolus vulgaris.

PMID- 16657212
TI  - Comparative studies of effect of auxin and ethylene on permeability and synthesis
      of RNA and protein.
AB  - The effects of ethylene on permeability and RNA and protein synthesis were
      assayed over a 6 to 26 hr period in tissue sections from avocado (Persea
      gratissima Gaertn. F., var. Fuerte), both pulp and peel of banana (Musa sapientum
      L., var. Gros Michel), bean endocarp (Phaseolus vulgaris L., var. Kentucky Wonder
      Pole beans) and leaves of Rhoeo discolor. Ethylene had no effect on permeability
      in 4 of the 5 tissues, but sometimes enhanced solute uptake in banana peel; it
      had either no effect or an inhibitory effect on synthesis of RNA and protein in
      sections from fruits of avocado and banana. Auxin (alpha-naphthalene acetic acid)
      stimulated synthesis of RNA and protein in bean endocarp and Rhoeo leaf sections,
      whereas ethylene inhibited both basal and auxin-induced synthesis. It is
      concluded that in these tissues the auxin effect is not an ethylene effect.

PMID- 16657213
TI  - Leaf water potential of differentially salinized plants.
AB  - Water and osmotic potential energies were measured with thermocouple
      psychrometers, at intervals during a 4-week period, in growing leaves of bean
      (Phaseolus vulgaris, var. Blue Lake) and barley (Hordeum vulgare, var. Liberty)
      plants having roots equally split between 2 differentially salinized nutrient
      solutions. The osmotic potentials of plants with half their roots in saline
      solutions were about halfway between the osmotic potentials of plants grown in
      nonsaline solutions and those grown in saline solutions. By the end of the 4-week
      measurement period, the beans and barley were almost mature. The final dry
      weights of shoots of plants with half their roots in saline solutions were about
      halfway between the dry weights of the shoots of plants grown in nonsaline
      solutions and the dry weights of those in saline solutions. The results obtained
      showed that the degree of osmotic adjustment and the rate of growth were
      functions of the proportion of the root system exposed to saline conditions.

PMID- 16657214
TI  - Effects of external cations and respiratory inhibitors on electrical potential of
      the xylem exudate of excised corn roots.
AB  - Glass capillary microelectrodes were used to study the electrical potential
      difference (PD) between the xylem exudate of excised corn roots, Zea mays L.
      Golden Bantam hybrid, and the external solution. A survey of the effects of
      various ions on the PD was made. With 1 mm single salt solutions, the PD was
      between 25 and 50 mv, exudate negative. The PD responded to concentration
      differences in single salt solutions of K(+), Na(+), and Ca(2+) in a manner
      suggestive of cation selectivity and cation diffusion potentials. With Ca(2+)
      present, the PD was insensitive to concentration changes of other cations.
      Substitution of NO(3) (-) for Cl(-) in K(+) solutions increased the PD by 2 to 5
      mv, although in general the PD showed little response to anion concentration
      changes. The PD was partially abolished by cyanide. The remaining fraction of the
      PD was sensitive to concentration changes in external K(+), and we postulate that
      the PD is the result of both a diffusion potential and an electrogenic pump.

PMID- 16657215
TI  - Translocation and distribution of picloram in bean plants associated with nastic
      movements.
AB  - Nastic responses in bean plants (Phaseolus vulgaris L. var. Black Valentine)
      occur rapidly when very low concentrations of picloram (4-amino-3,5,6
      trichloropicolinic acid) are applied to the root systems. The distribution of
      picloram associated with nastic responses was quantitatively determined in root
      treated plants.Sixty-seven micrograms of (14)C-labeled picloram and 72 mug of
      unlabeled picloram in 300 ml of nutrient solution were applied to roots of 9-day
      old bean plants growing in an environmental growth chamber at 24 degrees and 56%
      relative humidity. Plants were removed from the treatment solution after uptake
      periods of 3, 6, and 11 hr. Sections were excised from 10 locations on each plant
      and (14)C content was determined by liquid scintillation techniques. As a
      qualitative indication of picloram mobility, additional plants were treated for 3
      hr and subjected to autoradiographic analysis.The accumulation of picloram within
      various parts of the plant increased with treatment time. After 3 hr of picloram
      uptake, a curvature of 60 to 80 degrees from vertical in the upper 50 to 60 mm of
      stem corresponded to an accumulation in that part of the plant of 0.300 (second
      internode sample) to 1.065 (terminal bud sample) ng of picloram per mg fresh
      weight. The appearance of hyponasty in the trifoliolate leaflets after 6 hr of
      treatment corresponded to a picloram concentration in the leaf of 0.803 to 0.855
      ng per mg fresh weight.As evidenced by the (14)C count data, the translocation of
      picloram from the roots to the apical part of the plant was very rapid. Picloram
      was preferentially accumulated in the terminal bud and first trifoliolate
      leaflets. Very little picloram was transported to the primary leaves and only at
      the longer treatment periods. Autoradiographs of plants treated for 3 hr showed a
      qualitatively similar distribution of (14)C in the plant.

PMID- 16657216
TI  - Movement and Fate of p-Nitrophenyl-alpha,alpha,alpha-Trifluoro-2-Nitro-p Tolyl
      Ether-1'-C in Peanut Seedlings.
AB  - Autoradiographs and liquid scintillation counts of peanut (Arachis hypogaea L.,
      var. Starr) seedlings indicate that p-nitrophenyl-alpha,alpha,alpha-trifluoro-2
      nitro-p-tolyl ether-1'-(14)C (C-6989) is rapidly absorbed from nutrient solution
      but only 6.5% of the radioactivity absorbed is translocated to the shoot after
      144 hr, with the acropetal movement being confined to the stem and
      petiole.Metabolism of C-6989 by peanut seedlings proceeds rapidly, the major
      pathway being hydrolysis of the ether linkage and reduction of the 4-nitrophenol
      formed to 4-aminophenol. After 48 hr 4-aminophenol, C-6989 and 4-nitrophenol
      comprised 67.8, 17.4, and 13.5% of the total radioactivity recovered,
      respectively. After 144 hr these compounds comprised 94.3, 4.0, and 0.9% of the
      radioactivity, respectively.Reduction of one of the nitro groups of C-6989
      followed by hydrolysis of the ether linkage is a minor pathway of metabolism in
      peanut seedlings. Small amounts (less than 1.0% of the total radioactivity) of
      both p-mitrophenyl-alpha,alpha,alpha-trifluoro-2-amino-p-tolyl ether and p-amino
      phenyl-alpha,alpha,alpha-trifluoro-2-nitro-p-tolyl ether were present but no p
      aminophenyl-alpha,alpha,alpha-trifluoro-2-amino-p-tolyl ether was detected. Two
      very minor metabolites (less than 0.1% of the radioactivity) were detected which
      were not identified. These metabolites were possibly conjugates of the phenol
      derivatives with natural plant constituents, or products of substitution on, or
      ring cleavage of, the phenols.

PMID- 16657217
TI  - Flower formation in excised tobacco stem segments; I. Methodology and effects of
      plant hormones.
AB  - The formation of flowers has been studied in stem tissue excised from flowering
      plants of Nicotiana tabacum variety Wisconsin No. 38, and cultured in vitro on
      Murashige and Skoog nutrient medium. A procedure for quantitative evaluation of
      factors influencing floral expression has been developed and effects of the
      growth substances, indole-3-acetic acid (IAA), kinetin and gibberellic acid
      (GA(3)), on the process are reported.Although a low (1 mum) level of IAA was
      required for the development of normal flowers on stem segments, higher
      concentrations tended to inhibit flowering. The decrease in floral buds was rapid
      in the 3 to 15 mum range. IAA concentrations up to 75 mum increased vegetative
      bud formation so as to effect a transition from floral to vegetative buds rather
      than merely an inhibition of bud formation. Higher IAA concentrations inhibited
      both vegetative and floral bud formation.Kinetin in high concentrations greatly
      increased the number of vegetative buds but had no significant effect on the
      number of floral buds per segment. High kinetin concentrations also permitted
      branching of floral shoots so that flower clusters were formed.GA(3) applied in
      the medium from the start, strongly inhibited bud formation on the stem segments,
      but when applied to young floral buds after they had formed, it promoted their
      further development ("bolting").Flower formation occurred in complete darkness,
      but light of moderate intensity was required for the development of normal
      flowers.

PMID- 16657218
TI  - Flower Formation in Excised Tobacco Stem Segments; II. Reversible Removal of IAA
      Inhibition by RNA Base Analogues.
AB  - The RNA base analogues, 2-thiouracil, 6-azauracil and 8-azaguanine incorporated
      singly into the medium, increased the number of floral buds in excised stem
      segments of Nicotiana tabacum variety Wisconsin No. 38 cultured in vitro.
      Combined treatments with 2 and 3 base analogues were even more effective. The
      effects were prevented by the corresponding natural counterparts, uracil,
      uridine, and guanosine respectively. These nucleic acid constituents added to
      cultures without base analogues did not affect the number of floral buds formed.
      In stem segments from the lower internodes treatments with the analogues effected
      a transition from vegetative to floral bud formation, thus in a sense removing
      the floral gradient as defined by Chouard and Aghion.The inhibition of flower bud
      formation ordinarily achieved even with low concentrations of indole-3-acetic
      acid (IAA) was counteracted by low concentrations of 2-thiouracil, 6-azauracil
      and 8-azaguanine. Reversal to vegetative bud formation was not achieved even with
      high IAA concentrations in the presence of the base analogues.Stem segments
      excised from young, vegetative tobacco plants never formed floral buds in vitro.
      Thus, the inhibiting effect of IAA and the promoting effect of base analogues
      seem to be on the expression and not on the induction of flowering. The
      regulatory action of the IAA and base analogues in flower bud formation is
      tentatively ascribed to their differential effects on RNA synthesis.

PMID- 16657219
TI  - Environmentally-induced changes in the Fatty acids of chlorella.
AB  - Qualitative and quantitative analyses were made of the major fatty acids of
      Chlorella fusca, Shihira and Krauss, in both autotrophic and heterotrophic
      culture. Cells grown heterotrophically were subjected to CO(2) concentrations as
      great as 40%-in-air.The major fatty acids of autotrophic cells grown under a 1%
      environmental concentration of CO(2), in order of concentration were 16:0, 18:3,
      16:4, 18:2, 18:1, and 16:3. The analysis of heterotrophic cells at 1% CO(2), by
      comparison, indicated a complete absence of 16:4, reduced amounts of 18:3, and
      increased amounts of the other major acids.An increase in the environmental
      concentration of CO(2) (from 1%-30%) over the heterotrophic cultures produced a
      40% increase in total lipids and nearly a 50% increase in fatty acids. Palmitic
      acid (16:0) and 18:1 largely account for the fatty acid change by increasing from
      12 mg to 33 mg/g dry wt and 8 mg to 17 mg/g dry wt respectively. Possible
      explanations for this enhanced synthesis of fatty acids are suggested.

PMID- 16657220
TI  - Simulation of Cl Uptake by Low-salt Barley Roots as a Test of Models of Salt
      Uptake.
AB  - Computing techniques are used to simulate the course of uptake of K(+), Na(+),
      and Cl(-) by low-salt roots. Measurements of the fluxes of these ions in high
      salt roots are used to calculate membrane permeabilities, which are then used to
      calculate cell uptake. In this way it is possible to test the predictive value of
      different models for the location of sites of salt uptake in the cell.On the
      basis of the permeability data used, it is suggested that anion transport at the
      plasmalemma must be larger than that provided by Mechanism I and that there is a
      need for transport of both cations and anions at the tonoplast. To account for
      the observation that the level of salt at equilibrium in the tissue is very
      nearly independent of concentration, it is suggested that there must be some
      feedback from vacuolar content to rate of transport at the tonoplast.

PMID- 16657221
TI  - The effect of ultracentrifugation on fine structure and alpha-amylase production
      in barley aleurone cells.
AB  - Ultracentrifugation of barley aleurone cells results in the stratification of
      organelles thus allowing for a quantitation of those organelles. Gibberellic acid
      (GA(3))-stimulated alpha-amylase production in stratified cells is reduced by
      centrifugation at gravitational forces greater than 40,000g. Forces below 30,000g
      do not affect GA(3)-stimulated alpha-amylase production although stratification
      of organelles occurs at these forces. The ability of centrifuged cells to respond
      maximally to GA(3) by producing alpha-amylase is related to the degree of
      redistribution of organelles within these cells. Thus, recovery of cells from
      centrifugation at forces below 30,000g is rapid, while recovery from forces above
      40,000g is slow.

PMID- 16657222
TI  - On the Molecular Identity of ESR Signal II Observed in Photosynthetic Systems:
      The Effect of Heptane Extraction and Reconstitution With Plastoquinone and
      Deuterated Plastoquinone.
AB  - Speculation as to the identity of Signal II, the light-induced, broad, slow
      decaying electron spin resonance signal with hyperfine structure observed in
      photosynthetic materials, has tended to center on the semiquinone of
      plastoquinone. Experiments reported here were designed to give direct evidence
      bearing on that speculation. Heptane extraction of lipids from lyophilized
      spinach and tobacco chloroplast fragments reduced the amplitude of Signal II and
      increased the ratio of Signal I:Signal II. Reconstitution of the system by the
      addition of plastoquinone partially restored Signal II as well as the ratio of
      Signal I:Signal II to its pre-extraction condition. Addition of totally
      deuterated plastoquinone to extracted chloroplasts in which considerable Signal
      II had survived heptane extraction resulted in a spectrum which showed the
      characteristic hallmarks of Signal II observed in totally deuterated organisms.
      These results establish that a free radical immediately derived from
      plastoquinone contributes to Signal II. The data taken by themselves are
      consistent with plastochromanoxyl as well as plastosemiquinone free radicals
      giving rise to Signal II. Other contributors to Signal II are not ruled out.

PMID- 16657223
TI  - Stimulation of ethylene production in tomato tissue by propionic Acid.
AB  - Propionic acid (10(-3)m) increases ethylene production by about 30 to 60% in
      tissue from green and half-ripe tomatoes (Lycopersicon esculentum Mill. var.
      Homestead) but does not increase ethylene production in tissue from ripe fruit.
      Stimulation is not due to the conversion of propionic acid to ethylene but
      appears to be secondary in nature and to operate on the endogenous ethylene
      forming system. Thus conversion of methionine to ethylene in green and half-ripe
      tomato tissue is increased in the presence of propionic acid. Inhibitors which
      affect the normal endogenous ethylene-forming system similarly affect the
      propionic acid-stimulated system. Endogenous propionic acid may play a role in
      the regulation of ethylene production in tomato tissues.

PMID- 16657224
TI  - Photosynthetic studies with leaf cell suspensions from higher plants.
AB  - A technique for obtaining intact mesophyll cell suspensions derived from higher
      plant leaves is described. A large number of taxonomically unrelated plants were
      found suitable for cell ;extraction' including several plant species from
      monocotyledonous group.The absorption spectra of leaf cells in suspension
      differed only slightly from that of Chlorella cells. The higher plant cells
      respired and photosynthesized in aqueous solutions very much like algal cell
      suspensions. Only osmotically intact cells photosynthesized maximally and their
      activity was stimulated by 2 to several fold by the addition of bicarbonate to
      the medium. The isolated cells when stored at low temperature with proper
      aeration maintained their initial activity for a minimum of 9 hr. Cells stored at
      the room temperature (27 +/- 2 degrees ) lost their activity rather rapidly. The
      isolated cells were physiologically intact as tested by their metabolic response
      to diverse inhibiting chemicals and growth regulating substances.

PMID- 16657225
TI  - Factors related to iron absorption by enzymically isolated leaf cells.
AB  - The rate of Fe absorption by cells enzymically isolated from tobacco leaves is
      correlated with the age of the leaves from which the cells are derived. The cells
      obtained from younger leaves absorb Fe more rapidly than those from older ones.
      Ca inhibits Fe and Mn absorption. Fe and Mn are mutually antagonistic in their
      absorption by leaf cells. Ca enhances the inhibition of Mn absorption by Fe, but
      reduces the inhibition of Fe absorption by Mn. The affinity constant for Fe
      absorption by leaf cells is low. The chelate EDDHA (ethylenediamine di(o
      hydroxyphenylacetate) competitively inhibits Fe absorption.

PMID- 16657226
TI  - Effect of potassium deficiency upon translocation of C in attached blades and
      entire plants of sugarcane.
AB  - A deficiency in potassium decreased the translocation of labeled photosynthate
      from the leaf to the rest of the plant. Translocation was inhibited in blades
      which exhibited no visible symptoms of potassium deficiency and in which no
      decrease in photosynthesis was detected. In more severe deficiency both the rate
      of photosynthesis and the conversion of intermediates to end products decreased.
      The rate of respiration in deficient blades increased. The decrease in
      translocation caused by potassium deficiency is considered to be a primary effect
      and not secondary to the development of the well-known symptoms of potassium
      deficiency.

PMID- 16657227
TI  - Dormancy regulation in subterranean clover seeds by ethylene.

PMID- 16657228
TI  - Postharvest response of oranges to ethylene.

PMID- 16657229
TI  - Occurrence of RNA in glyoxysomes from castor bean endosperm.

PMID- 16657230
TI  - Evidence for the presence of protochlorophyllase in etiolated wheat seedlings.

PMID- 16657231
TI  - Independence of Lateral and Differential Longitudinal Movement of Indoleactic
      Acid in Geotropically Stimulated Coleoptiles of Zea mays.
AB  - The possible interdependence of the differential longitudinal, and the lateral
      movement of indoleacetic acid (IAA) in horizontal Zea coleoptile segments has
      been examined. The coleoptiles have been opened out into flat pieces of tissue
      and supplied apically with IAA-1-(14)C.Opened-out segments orientated so that all
      the cells correspond with those at the ;bottom' of a normal horizontal
      coleoptile, transport more IAA basipetally than do segments in which all the
      cells are equivalent to those at the ;top' of the horizontal coleoptile.In opened
      out segments orientated so that all the cells are equivalent to those at the side
      of the horizontal coleoptile cylinder, there is no difference in the basipetal
      transport capacity of the upper and lower halves. This is so even if the tissue
      has been in the horizontal position for 90 min before being bisected into its
      upper and lower halves. In this ;side' tissue, however, there is a polarized
      downward movement of IAA. At least 95% of the (14)C in both the upper and lower
      halves of the tissue is confined to the IAA molecule.In horizontal Zea
      coleoptiles the polarized lateral movement of IAA can therefore occur
      independently of the differential basipetal transport of IAA in the upper and
      lower halves of the organ.

PMID- 16657232
TI  - Acid-soluble nucleotides of pinto bean leaves at different stages of development.
AB  - Acid-soluble nucleotides of unifoliate leaves of Pinto bean plants (Phaseolus
      vulgaris L.) were determined at young, mature, and senescent stages of
      development. At least 25 components could be distinguished on the basis of
      inorganic phosphorus determinations and 37 or more fractions on the basis of
      (32)P labeling, with adenosine di- and triphosphates accounting for 60% of the
      total moles of nucleotide. The total nucleotide P and inorganic P, on a fresh
      weight basis, decreased about 44% between each stage of leaf development, but
      decrements in the levels of individual nucleotides varied from this over-all
      pattern.Minor changes in the relative abundance of the individual nucleotides
      accompanied aging although the percentage of purine-containing nucleotides
      decreased with age. Total (32)P activity per leaf in the nucleotide pool
      increased about 3-fold between the young and mature leaves and decreased slightly
      as leaves became senescent. In general, the specific activities of the
      nucleotides increased with increased age and adenosine-, guanosine-, uridine-,
      and cytidine triphosphates and adenosine diphosphate accounted for approximately
      90% of the total activity. The changes in the relative sizes and energy status of
      the nucleotide pools were not so obvious as the changes in other metabolites that
      have been reported to accompany aging in leaf tissue.

PMID- 16657233
TI  - Effect of pyrophosphate on photosynthetic electron transport reactions.
AB  - Inorganic pyrophosphate is found to inhibit the ferredoxin-dependent
      photoreduction of NADP by isolated chloroplasts. The reduction of ferricyanide is
      not inhibited, nor is the activity of photosystem 1 as measured with methyl
      viologen as the electron acceptor. All other ferredoxin-depended reactions are
      inhibited, such as cytochrome c photoreduction and the reaction sequence: NADPH -
      >Flavoprotein-->ferredoxin-->cytochrome c. The inhibition by pyrophosphate is, in
      all cases, competitive with ferredoxin and independent of NADP concentration.
      Pyrophosphate inhibition of the formation of the ferredoxin-flavoprotein complex
      is demonstrated spectrophotometrically.

PMID- 16657234
TI  - Photophosphorylation during Chloroplast Development in Red Kidney Bean. I.
      Characterization of the Mature System and the Effect of BSA and Sulfhydryl
      Reagents.
AB  - Optimal conditions were determined for photophosphorylation and reduction in
      mature chloroplasts from Phaseolus vulgaris var. Red Kidney. Bovine serum albumin
      (BSA) at 1 mg/ml and various sulfhydryl reagents (0.1-0.5 mm) greatly enhanced
      cyclic and noncyclic phosphorylation, but had little effect on photoreduction.
      BSA and reduced glutathione also stimulated cyclic phosphorylation in spinach
      chloroplasts. BSA was needed in the reaction from the start to provide high rates
      of phosphorylation. BSA also protected against atebrin uncoupling but not against
      uncoupling by ammonium ions or inhibition by 3,-(3,4-dichlorophenyl)-1,1
      dimethylurea. Similarly, BSA and glutathione protected against atebrin inhibition
      of cyclic phosphorylation. Chloroplasts incubated at 0 degrees rapidly lost the
      ability to catalyze phosphorylation and BSA did not protect against inactivation.

PMID- 16657235
TI  - Accumulation of potassium and sodium by barley roots in a k-na replacement
      series.
AB  - Excised roots of barley (Hordeum vulgare, var. Campana) were incubated for 24 hr
      in solutions containing constant total concentrations of KCl and NaCl but in
      which the mole fractions of K and Na were varied in replacement series. In
      solutions containing 1, 10, or 50 mm concentrations of K(+) plus Na(+), total
      cation accumulation was dependent upon the total salt concentration but was
      relatively independent of the mole fractions of K(+) and Na(+). These results
      imply that accumulation of K(+) and Na(+) was limited by a common factor. In
      solutions containing 0.01 mm K(+) plus Na(+) there was a strong preference for
      K(+) over Na(+) and the sum of K(+) and Na(+) accumulation increased with
      increasing K(+) concentration.In the replacement series utilizing 0.1 mm K(+)
      plus Na(+), K(+) accumulation reached a peak at solution concentrations of 0.04
      mm K(+) and 0.06 mm Na(+). Potassium accumulation then decreased as Na(+) was
      further replaced by K(+) to concentrations of 0.06 mm K(+) and 0.04 mm Na(+).
      Potassium accumulation again increased with additional replacement of Na(+) by
      K(+).

PMID- 16657236
TI  - The Formation of Ribulose Diphosphate Carboxylase Protein during Chloroplast
      Development in Barley.
AB  - Ribulose 1,5-diphosphate carboxylase is synthesized in barley leaves growing in
      the dark. Upon illumination there is a marked increase in the rate of synthesis
      of the enzyme. The specific activity of the enzyme expressed as cpm incorporated
      into phosphoglyceric acid per mug of fraction I protein, after isolation shows no
      change either during dark growth or greening. During early stages of illumination
      of 7 day dark grown leaves with 320 foot-candles the enzymic activity in the
      water soluble protein fraction of the leaf shows a short term decline after 15
      min which lasts for 30 min. Leaves greening at 2 foot-candles show a similar
      decline which is shifted to a time between the fourth and eighth hr after the
      onset of illumination.

PMID- 16657237
TI  - Kinetic Behavior of Electron Paramagnetic Resonance Signal I. II Comparison of
      Wild Type and Mutant (ac-206) Chlamydomonas reinhardtii.
AB  - The electron paramagnetic resonance (EPR) characteristics of wild type
      Chlamydomonas reinhardtii are compared with those of a mutant strain (ac-206)
      which lacks cytochrome 553. The steady-state signals I and II are similar but
      differ in their responses to light of long and short wavelengths, reflecting the
      fact that the electron transport chain linking photosystems I and II is
      interrupted. The kinetic behavior of signal I is simpler in the mutant, which
      lacks induction effects prominent in the wild type. The decay of the signal when
      light ceases is not dependent on the length or intensity of illumination in the
      mutant, whereas it is in the wild type. These data can be interpreted in terms of
      signal I being a reflection of cyclic flow in a pathway which does not involve
      cytochrome 553 in the mutant, whereas in the wild type there is also a
      contribution of electrons from photosystem II.

PMID- 16657238
TI  - Stomatal Diffusion Resistance of Snap Beans. II. Effect of Light.
AB  - The effect of light on the stomatal resistance of abaxial and adaxial leaf
      surfaces of snap beans (Phaseolus vulgaris L.) was studied in the growth chamber
      and in the field. The adaxial stomata required more light to open than the
      abaxial stomata; the abaxial stomatal apertures were still about 50% open at 1%
      full sunlight and light-induced closure was never observed under daytime field
      conditions. A given value of abaxial stomatal resistance was obtained at a given
      illumination of the abaxial guard cells whether illumination was adaxial or
      abaxial.

PMID- 16657239
TI  - Stomatal diffusion resistance of snap beans. I. Influence of leaf-water
      potential.
AB  - Concurrent measurements of abaxial and adaxial stomatal resistance and leaf-water
      potentials of snap beans (Phaseolus vulgaris L.) in the field and growth chamber
      show that the stomata on the 2 surfaces of the leaflet react differently to water
      deficit. The stomata on the abaxial surface, which are about 7 times more
      numerous than on the adaxial surface, are not significantly affected at leaf
      water potentials greater than -11 bars, but with further decrease in leaf-water
      potential, the resistance rapidly increases. On the other hand, the resistance of
      the adaxial stomata increases sharply at a leaf-water potential of about -8 bars
      and is constant at higher water potentials. The average stomatal resistance for
      both surfaces of the leaf, which is the major diffusive resistance to water
      vapor, to a first approximation acts as an on-off switch and helps prevent
      further decline in leaf-water potential. The relation between the leaf-water
      potential and the stomatal resistance links the soil-water potential to the
      transpiration stream as needed for soil-plant-atmosphere models.

PMID- 16657240
TI  - IAA Oxidase Inhibitors from Normal and Mutant Maize Plants.
AB  - Extracts of maize (Zea mays L.) plants contain substances which, in vitro,
      inhibit an indoleacetic acid (IAA) oxidase enzyme from maize. The extracts can be
      freed of inhibitors by dialysis or by passage through columns of
      polyvinylpyrrolidone powder. Inhibitor-free extracts contain an IAA oxidase
      enzyme which requires a phenolic co-factor and is stimulated by Mn(2+).IAA
      oxidase inhibitor and total phenol levels were compared for normal maize and for
      the maize mutant Knotted (Kn). In plants up to 18 days old the level of heat
      stable, water soluble IAA oxidase inhibitors increases with increasing dosage of
      the Kn allele. Increased inhibitor content is accompanied, but not paralleled, by
      increased content of total phenols. Although several inhibitors are present in
      crude extracts, most inhibition can be attributed to 1 compound. This compound is
      not destroyed by horseradish peroxidase in the absence of IAA. At pH 3.5 it is
      not extracted into ether, but it is rendered ether-extractable by incubation in 2
      n KOH for 5 hr at room temperature. This compound is tentatively identified as an
      ester of ferulic acid and some unknown moiety.

PMID- 16657241
TI  - Multiple molecular forms of ficin-evidence against autolysis as explanation.
AB  - While the total amount of proteolytic enzyme activity in the latex from Ficus
      carica varieties Kadota and Black Mission showed seasonal variation and was
      different between the 2 crops of figs in the latex collected at the same time and
      from the same tree, there is no difference in the number of multiple molecular
      forms of ficin present as demonstrated by chromatography on carboxymethyl
      cellulose. The number of multiple forms of ficin is also the same, with 1
      exception, among samples of latex which have been collected with no protection
      against proteolysis, samples which have been collected directly into sodium p
      chloromercuribenzoate to inhibit all proteolysis and samples which have been held
      at an elevated temperature so as to encourage proteolysis. Evidence is presented
      to support the proposal that component C of Ficus carica variety Kadota is not
      present in the original latex but that it is produced from component D during the
      purification procedure. The data support the hypothesis that, with the possible
      exception of 1 component, the multiple molecular forms of ficin are not the
      result of artifacts produced by autolysis during collection, storage and
      purification of the sample.

PMID- 16657242
TI  - Nature of the Conversion of Ficus carica Variety Kadota Ficin Component D to
      Component C. Some Physicochemical Properties of Components C and D.
AB  - Component C can be formed from component D under the experimental conditions used
      during purification of Ficus carica variety Kadota latex. By use of the
      inhibitor, sodium p-chloromercuribenzoate, the 2 components have been purified to
      chromatographic homogeneity. The 2 components have identical molecular weights
      and amino acid composition. The only difference found between the 2 components is
      the presence of 3 to 6 more amide groups in component D than in component C.
      There also appears to be a conformational difference between the 2 since
      component C is not as acidic, with respect to component D, as would be expected
      from the comparative amide contents. Conformational differences between the 2 are
      also indicated by the chromatographic behavior of the 2 in the presence and
      absence of sodium-p-chloromercuribenzoate.

PMID- 16657243
TI  - Multiple Molecular Forms of Ficus glabrata Ficin. Their Separation and Relative
      Physical, Chemical, and Enzymatic Properties.
AB  - Six of the proteolytic enzyme components of Ficus glabrata ficin have been
      isolated and shown to be chromatographically homogeneous. The molecular weights,
      the amino acid compositions, the electrophoretic and chromatographic behavior of
      the tryptic peptides, and the relative specificities of these 6 components have
      been determined. Within the experimental precision of the methods all 6
      components are identical. They also have identical solubilities in sodium
      chloride and ammonium sulfate solutions. However, they are markedly different in
      their chromatographic properties. These multiple molecular forms of Ficus
      glabrata ficin may differ only in their conformational forms (conformers) or they
      may have minor differences in amino acid sequences which are sufficient to give
      different conformations and yet not be detected by the usual peptide mapping
      techniques. At the moment, we favor the latter possibility.

PMID- 16657244
TI  - Ethylene and carbon dioxide in the growth and development of cultured radish
      roots.
AB  - Ethylene is produced by cultured radish roots in amounts large enough to be
      physiologically important. When roots were grown in controlled atmospheres,
      applied ethylene was generally inhibitory to elongation, lateral root initiation,
      and cambial activity. 1% CO(2) similarly affected roots not given ethylene. In
      contrast, elongation and lateral root production of ethylene-treated roots were
      stimulated by 1% CO(2). The results suggest that the often-observed stimulation
      of root growth by CO(2) is due to an interaction with endogenous ethylene.

PMID- 16657245
TI  - Cytochrome Oxidase Activity in Blastocladiella emersonii.
AB  - Studies of cytochrome oxidase in isolated mitochondria of Blastocladiella
      emersonii Cant. and Hyatt show that the enzyme was present in zoospores and
      throughout the development of ordinary colorless sporangia and of resistant
      sporangia. The enzyme activity was present in KCl, NaCl, NH(4)Cl, and KHCO(3)
      induced resistant sporangia, and was shown to be as active or more active than
      the enzyme found in ordinary colorless sporangia and zoospores. Interfering
      substances causing difficulties in the measurement of cytochrome oxidase activity
      were found in whole cell homogenates of KHCO(3) grown resistant sporangia, but
      not in KCl, NaCl, or NH(4)Cl grown thalli. These substances could be removed by
      dialysis or by sedimentation of the mitochondria.

PMID- 16657246
TI  - Plant suspension culture media macromolecules-pectic substances, protein, and
      peroxidase.
AB  - Macromolecules secreted into the media by a nondifferentiating suspension culture
      of tobacco cells were found to be composed of protein and polysaccharide, and to
      account for the viscosity of the media. The concentration, composition, and
      viscosity of these macromolecules changed significantly with the age of the
      culture and growth temperature. The concentration changed from 0.02 mg/ml in
      newly inoculated cultures to over 1 mg/ml in older cultures. The macromolecules
      contained from 6 to 18% protein and 3 to 4 mumoles hydroxy-proline/mg nitrogen,
      more than 20 times the level found in whole cells. The macromolecules contained 5
      to 25% pectic substances whose carboxyl groups were either methyl esterified or
      combined with calcium. Arabinose, xylose, glucose, galactose, and mannose were
      identified in acid hydrolysates of the macromolecules. Peroxidase activity of the
      macromolecules increased as cultures became older. Peroxidase isoenzyme patterns
      changed with culture age and growth temperature. The relation of the
      macromolecules to cell walls and intercellular substances is discussed.

PMID- 16657247
TI  - Synergistic effects of metabolically related amino acids on the growth of a
      multicellular plant.
AB  - The effects of several amino acids related to the metabolism of aspartic acid on
      the growth and development of gemmalings of the liverwort Marchantia polymorpha
      were investigated under axenic conditions. Lysine and theonine synergistically
      inhibit the growth of these plants and cause a loss of normal pigmentation at
      concentrations as low as 1 mum. These effects are highly specific for this pair
      of amino acids, are partially reversible upon removal of the effectors, and can
      be prevented by low concentrations of methionine or its metabolic precursor,
      homoserine. Alterations in the growth and development of gemmalings in the
      presence of natural amino acids are discussed in relation to metabolic regulatory
      mechanisms which have been well established in microorganisms.

PMID- 16657248
TI  - Plastid development in albescent maize.
AB  - Plastid development in albescent (al/al) and wild-type (+/al) strains of Zea mays
      has been studied in the electron microscope. Etiolated seedlings of the mutant
      are severely deficient in colored carotenoid pigments and accumulate carotenoid
      precursors tentatively identified as phytoene and phytofluene. The fine structure
      of proplastids in etiolated wild-type and mutant leaves is similar with 1 notable
      exception. Osmiophilic bodies found in the wild-type were lacking in all sections
      of albescent proplastids examined suggesting that these structures may be storage
      centers for carotenoid pigments. Plastid pigments are destroyed, chlorophyll
      synthesizing potential is lost, and the ultrastructure of plastids is
      irreversibly altered when mutant seedlings are placed directly in high intensity
      light. However, synthesis of plastid pigments and development of the
      photosynthetic apparatus as seen in the electron microscope is normal, and
      indistinguishable from that in the wild-type, in seedlings of the albescent
      mutant preilluminated with low intensity light prior to high intensity
      illumination. During treatment in low intensity light carotenogenesis is
      initiated in the mutant and proceeds normally thereafter.

PMID- 16657249
TI  - Nonphotosynthetic retardation of chloroplast senescence by light.
AB  - Excised apical portions of green wheat leaf sections were treated with
      aminotriazole to prevent formation of new chloroplasts. Illumination retarded the
      decline in chlorophyll content per leaf section, the disintegration of
      chloroplast ultrastructure, and the loss of capacity for photosynthetic carbon
      fixation. We interpret these 3 effects of illumination as facets of a single
      light effect in retarding chloroplast senescence. This light effect in retarding
      chloroplast senescence has features differing from characteristics of
      photosynthetic carbon fixation. For example, A) application of the photosynthetic
      inhibitor 3-(3,4-dichlorophenyl)-1, 1-dimethylurea did not decrease, and may have
      even slightly increased, the effectiveness of light; B) although the action
      spectrum contains peaks in the blue and red regions, it differs from the action
      spectrum for photosynthetic CO(2) assimilation in wheat; C) in
      nonphotosynthesizing tissue, application of sugars did not retard chloroplast
      senescence; D) light saturation was achieved by only a few hundred
      microwatts/cm(2). Considered together with the well-known light requirement for
      chloroplast formation, our results indicate that light has a dual,
      photomorphogenetic control in maintaining the green status of the plant by also
      exerting a second effect: retarding of senescence of chloroplasts already
      present.

PMID- 16657250
TI  - Properties and Ultrastructure of Phycoerythrin From Porphyridium cruentum.
AB  - Phycoerythrin, a photosynthetic accessory pigment, was isolated from Porphyridium
      cruentum and examined by electron microscopy and disc gel electrophoresis. The
      absorption monomer, with maxima at 563, 545, and a shoulder at 500 nm, has a
      molecular weight of about 300,000. With phosphotungstic acid staining it appears
      as a tightly structured disc-shaped particle possessing a mean diameter of 101 +/
      0.4A and height of 54 +/- 0.7A. The absorption maxima remained the same in
      glutaraldehyde fixed material, and in dimer and trimer aggregates. Treatment with
      sodium dodecyl sulfate caused a breakdown into smaller units accompanied by a
      loss of the 563 nm peak. It is suggested that this absorption monomer is the in
      vivo functional species and comparable to the phycocyanin hexamer, but
      structurally distinguishable at the ultrastructural level. It has been calculated
      that about 35 phycobiliprotein molecules can be contained within each
      phycobilisome. There are 1.4 x 10(3) chlorophyll molecules per phycobilisome, but
      not contained within it.

PMID- 16657251
TI  - Role of the accompanying anion in the effect of calcium salts on potassium uptake
      by excised barley roots.
AB  - The effect of addition of Ca salts on accumulation of K from 5 mN KCl or
      K(2)SO(4) solutions was found to depend on whether Ca was added as Cl or SO(4)
      salt. Chloride as well as K uptake was increased when Ca and Cl concentrations in
      culture solutions were increased. Pre-treatment of roots with CaCl(2) stimulated
      subsequent K uptake from K(2)SO(4) solutions as compared to pre-treatment with
      distilled water but pre-treatment with CaSO(4) did not. The results indicate that
      addition of Ca salts to KCl or K(2)SO(4) solutions increased anion uptake and the
      effect of the addition of the Ca salts on K uptake was in part the result of
      increased anion uptake and not entirely a direct effect of Ca.In contrast,
      accumulation of Na and K from solutions containing these ions as SO(4) or Cl
      salts was changed from preferential uptake of Na to preferential uptake of K by
      addition of either CaCl(2) or CaSO(4). Thus, while Ca salts may influence K
      accumulation partly as a result of effects on anion uptake, the selectivity for K
      uptake depends on the presence of Ca and is influenced little by the accompanying
      anion.

PMID- 16657252
TI  - Photoreduction of 2,6-dichlorophenolindophenol by diphenylcarbazide: a
      photosystem 2 reaction catalyzed by tris-washed chloroplasts and subchloroplast
      fragments.
AB  - The use of diphenylcarbazide as an electron donor coupled to the photoreduction
      of 2,6-dichlorophenolindophenol by tris-washed chloroplasts or subchloroplast
      fragments provides a simple and sensitive assay for photosystem 2 of
      chloroplasts. By varying the concentration of tris buffer at pH 8.0 during an
      incubation period it is shown that the destruction of oxygen evolution activity
      is accompanied by a corresponding emergence of an ability to photooxidize
      diphenylcarbazide, as evidenced by absorbance changes due to diphenylcarbazide at
      300 nm. The temperature-sensitive oxidation of diphenylcarbazide is inhibited by
      DCMU and by high ionic strengths. This activity appears to measure the primary
      photochemical reaction of photosystem 2.

PMID- 16657253
TI  - The induction of nitrate reductase and the preferential assimilation of ammonium
      in germinating rice seedlings.
AB  - Nitrate reduotase is induced by nitrate in excised embryos and germinating intact
      seedlings of rice (Oryza sativa L.). The enzyme is induced 24 hr after
      imbibition. The rate of enzyme formation increases with the age of seedlings.
      There is a lag period of 30 to 40 min between the addition of substrate and the
      formation of nitrate reductase. Formation of the enzyme is promoted by the
      presence of ammonium. Chloramphenicol, actinomycin D and cycloheximide
      effectively inhibit the formation of nitrate reductase.Rice seedlings can
      assimilate nitrate from the beginning of germination. However, the utilization of
      nitrate is completely suppressed by the presence of ammonium. As soon as ammonium
      is depleted from the medium, nitrate utilization is resumed. Ammonium inhibits
      the first step of nitrate reduction, i.e., NO(-) (3) --> NO(-) (2), but does not
      inhibit the assimilation of nitrite. This provides an example of feedback
      inhibition in higher plants.

PMID- 16657254
TI  - Translocation and accumulation of translocate in the sugar beet petiole.
AB  - Accumulation of translocate during steady-state labeling of photosynthate was
      measured in the source leaf petioles of sugar beet (Beta vulgaris L. monogerm
      hybrid). During an 8-hr period, 2.7% of the translocate or 0.38 mug carbon/min
      was accumulated per cm petiole. Material was stored mainly as sucrose and as
      compounds insoluble in 80% ethanol. The minimum peak velocity of translocation
      approached an average of 54 cm/hr as the specific activity of the (14)CO(2) pulse
      was progressively increased. The ratio of cross sectional area required for
      translocation to actual sieve tube area in the petiole was 1.2. A regression
      analysis of translocation rate versus sieve tube cross sectional area yielded a
      coefficient of 0.76. The specific mass transfer rate in the petiole was 1.4 g/hr
      cm(2) phloem or 4.8 g/hr cm(2) sieve tube. Histoautoradiographic studies
      indicated that translocation occurs through the area of phloem occupied by sieve
      tubes and companion cells while storage occurs in these cells plus cambium and
      phloem parenchyma cells. The ability of the petiole to act as a sink for
      translocate is consistent with the concept that storage along path tissue serves
      to buffer sucrose concentration in the translocate during periods of fluctuating
      assimilation.

PMID- 16657255
TI  - Symbiotic effectiveness and n(2) fixation in nodulated soybean.

PMID- 16657256
TI  - Simultaneous reactivation of ultraviolet damage in xanthium leaves.
AB  - Experiments on Xanthium leaf discs were carried out to determine whether
      concomitant photoreactivation could be detected and if so, to compare its effects
      with photoreactivation due to post-irradiation treatments. Attempts mere made to
      simulate certain intensities of unfiltered solar radiation. A small but definite
      amount of simultaneous reactivation was observed. The dose reduction factor
      averaged 0.57. It was not clear whether the reactivation was due mainly to direct
      photoreactivation, photoprotection, or to heating effects. A much larger amount
      of reactivation due to post-irradiation treatments (direct photoreactivation) was
      noted with the dose reduction factor averaging 0.30.

PMID- 16657257
TI  - Effect of sublethal and lethal temperature on plant cells.
AB  - Soybean, Glycine max L., and elodea, Elodea canadensis Michx, leaves were exposed
      to sublethal and lethal temperatures and examined by light microscopy. Loss of
      chlorophyll and swollen chloroplasts were observed in cells of elodea leaves
      exposed to sublethal temperatures. At the thermal death point of leaf cells of
      elodea and soybean, there was a disorganization of the tonoplast membrane,
      plasmalemma, and chloroplast membranes. Approximately 40% of the cells in elodea
      and 50% of the cells in soybean leaves exhibited oriteria of cell death when
      exposed to a temperature which induced necrotic leaf tissue. Plasmolysis of leaf
      cells of elodea and soybean occurred at lethal temperatures, but did not appear
      to be the primary cause of cellular death. The primary effect of lethal
      temperatures on the leaf cells used in these experiments is disintegration of the
      cellular membranes.Following exposure of attached elodea leaves to lethal
      temperatures, changes in leaf cells were periodically observed with a light
      microscope. In low temperature treatments, (43 through 52 degrees ), the
      percentages of cells exhibiting criteria of death 12 days after treatment did not
      change from the percentages determined immediately after treatment. All
      treatments above 52 degrees resulted in 40% or more of the cells exhibiting
      criteria of cell death immediately after treatment. In these treatments, this
      resulted in all cells exhibiting criteria of death on the fourth day after
      treatment.

PMID- 16657258
TI  - Ethylene modification of an auxin pulse in cotton stem sections.
AB  - The effect of ethylene on the basipetal movement of indole-3-acetic acid-1-(14)C
      through cotton stem sections (Gossypium hirsutum, L. var. Stoneville 213) was
      studied apart from processes involved in the uptake and exit of auxin by the
      section. Stem sections 60 mm in length were pretreated with ethylene or placed in
      room air (control) and pulse labeled for 20 min with IAA-1-(14)C. In both the
      ethylene treated and control sections, the IAA-1-(14)C taken up moved basipetally
      as a peak of radioactivity. Generally, the applied pulse moved down the stem
      sections at an average velocity of approximately 5.8 mm per hr. In some
      experiments, however, ethylene slightly reduced the velocity of auxin transport.
      Although the peak of radioactivity became broader and more dispersed during its
      migration through the section, it was still distinguishable after 7 hr of
      transport.As the ethylene pretreatment periods were increased from 1.5 to 3.0 hr
      there was a progressively greater loss of activity from the pulse of applied IAA
      1-(14)C during its basipetal movement. On the average, 4% more activity was lost
      from the applied pulse at 1.5 hr, 15% more at 2.0 hr and 26% more at 3.0 hr when
      compared to control stem sections.The data establish that ethylene inhibits auxin
      transport in vivo, and it is proposed that the effect is due possibly to
      increased rates of auxin immobilization.

PMID- 16657259
TI  - Similarities between gibberellins and related compounds in inducing Acid
      phosphatase and reducing sugar release from barley endosperm.
AB  - Barley endosperm halves release acid phosphatase in response to several
      gibberellins and gibberellin precursors. Seed halves incubated with 10(-7)m GA(3)
      at 29 degrees begin to release phosphatase after 11 hr and release it for another
      26 hr in response to GA(3). After 37 hr, the rate of release slows to that of
      seed halves incubated without GA(3). GA(3) is active at 10(-10)m and maximally
      active at 10(-7)m. Comparative activity of 12 gibberellins and gibberellin
      precursors is GA(1) = GA(3) > GA(2) > GA(4) = GA(7) > GA(5) = GA(13) > GA(14) >
      GA(8) = GA(9) > (-)kaurenoic acid > (-)-kaurene. These compounds show the same
      order of activity and approximately the same relative activity in inducing
      reducing sugar release as in inducing phosphatase activity. The activity of each
      compound increases with its presumed position in a biosynthetic pathway leading
      from kaurene to GA(3). This correlation suggests that activity may be a
      reflection of the efficiency of conversion to an active form within the seed
      half.The ease of measuring the acid phosphatase response and the sensitivity of
      the seed halves to low concentrations of many gibberellins and gibberellin
      precursors makes this a useful bioassay for gibberellin-like substances.

PMID- 16657260
TI  - The Control of Growth Habit of Marquillo x Kenya Farmer Wheat Dwarf I by
      Temperature.
AB  - The Marquillo x Kenya Farmer 1 "grass-clump" dwarf selection of Triticum aestivum
      L. was grown under continuous 2000 foot candle light and several regimes of
      alternating 16 degrees and 26 degrees temperatures combined in total cycle
      lengths of 6, 12, 24, or 48 hr. Plants at 26 degrees grew as normal wheat. Those
      exposed to 0.25 to 2 hr of 16 degrees per cycle showed typical "grass-clump"
      dwarf characteristics which were independent of the cycle length. Treatments with
      16 degrees exposures of 4 to 8 hr per 24 hr and 12 to 16 hr per 48 hr exhibited
      vegetative "grass-clump" dwarfness for 40 days but later displayed extensive
      reproductive development. Longer 16 degrees treatments killed the plants at a
      very early stage of vegetative development before floral initiation. The data
      supported an hypothesis that all 4 growth habits were related to the temperature
      sensitivity of the vegetative meristem. The cessation of meristem development was
      possibly due to the accumulation of a stable inhibitory substance produced at low
      temperatures.

PMID- 16657261
TI  - Activity of pectin esterase and cellulase in the abscission zone of citrus leaf
      explants.
AB  - The activity of pectin esterase and cellulase in abscission of citrus explants
      was studied. No relation was established between pectin esterase and abscission,
      while cellulase activity was markedly increased before abscission and for a
      certain period after excision. IAA and cycloheximide delay abscission and
      cellulase activity, while ethylene and, to a lesser extent, GA(3) accelerate
      them. Application of cycloheximide during the lag period and before cellulase
      activity can be measured, inhibits to a certain extent the formation of
      cellulase. An escape from the inhibitory effect of cycloheximide is detected when
      inhibitor is supplied at the end of the lag period.

PMID- 16657262
TI  - Relation of CO(2) Compensation Concentration to Apparent Photosynthesis in Maize.
AB  - Significant differences in CO(2) compensation concentration measured in the field
      among varieties of the species Zea mays L. are reported for the first time. CO(2)
      compensation concentrations were significantly (P</= 0.01) and negatively
      correlated with apparent photosynthesis at 300 mul CO(2)/liter air. The Michaelis
      constant (as defined) for a leaf was significantly (P</= 0.01) and positively
      correlated with apparent photosynthesis among varieties. While the first
      correlation is similar to behavior of CO(2) compensation among species of
      different photosynthetic efficiency, the latter correlation is the converse of
      the behavior of Km among species.

PMID- 16657263
TI  - Changes in Nucleic Acid Fractions of Seed Components of Red Pine (Pinus resinosa
      Ait.) during Germination.
AB  - Changes in nucleic acid fractions of Pinus resinosa during seed germination were
      studied. At various stages of seed germination, embryos and megagametophytes were
      surgically separated and nucleic acids were extracted separately by a phenol
      method. Total nucleic acids were fractionated on single-layer methylated albumin
      kieselguhr (MAK) columns. Total nucleic acids in embryos increased significantly
      2 days after seeds were moistened, whereas, in megagametophytes, total nucleic
      acids stayed almost at a constant level until they degenerated at the time of
      shedding. In embryos, ribosomal RNAs (rRNA) increased 2 days after seeds were
      sown, whereas soluble RNA (sRNA) increased at 3 days. By comparison, nucleic acid
      fractions of megagametophytes did not show any quantitative changes during
      germination, except that rRNA fractions decreased shortly before shedding of seed
      coats. In dormant embryos the proportion of DNA was high and the proportions of
      sRNA and rRNA were low, whereas in megagametophytes at dormancy the proportions
      were completely reversed. As seed germination progressed, proportions of nucleic
      acid fractions in embryos changed significantly. In megagametophytes, although
      proportions of individual fractions remained almost constant throughout the
      experimental period, incorporation of (32)P into sRNA and rRNA of
      megagametophytes indicated turnover of these fractions.

PMID- 16657264
TI  - Phytochrome in cultured wild carrot tissue. I. Synthesis.
AB  - Stable levels of P(FR) occur in light-grown suspension cultures of wild carrot.
      Upon darkening such tissue, P(R) accumulates until the high P(R) level
      characteristics of dark-grown tissue is reached. Data are compatible with the
      idea of an equilibrium between processes of synthesis and destruction in tissue
      grown in the light. Reappearance of phytochrome also follows light-induced
      pigment destruction in dark-grown tissue. The rate of P(R) appearance is similar
      in both cases. The rate of disappearance of P(FR), however, is slower in light
      grown tissue than in dark-grown tissue.

PMID- 16657265
TI  - A Simple Method to Obtain High Frequency of Stalk Division in Acetabularia
      mediterranea.

PMID- 16657266
TI  - Methyl chlorophyllide a as a probable intermediate in the chlorophyll a pathway.

PMID- 16657267
TI  - Isolation of octopamine from annual rye grass.

PMID- 16657268
TI  - Floral Induction in a Short-Day Plant, Plumbago indica L., by 2
      Chloroethanephosphonic Acid.

PMID- 16657269
TI  - Studies on Flowering Responses of Urena lobata.
AB  - Urena lobata L. is a qualitative short-day plant with a critical dark period of
      about 12 hr. A minimum of 12 short days are required for floral initiation.
      Gibberellic acid (GA(3)) sprayed onto the leaves promoted flowering. The growth
      retardant, (2-chloroethyl)-trimethylammonium chloride (CCC) markedly inhibited
      flowering and stem elongation. This inhibition was reversed by subsequent
      application of GA(3).

PMID- 16657270
TI  - Effects of decenylsuccinic Acid on p uptake and translocation by barley and
      winter wheat.
AB  - After 3 days of exposure to 10(-3) and 10(-4) M decenylsuccinic acid, winter
      wheat plants wilted and died. Decenylsuccinate at 10(-3) M inhibited (32)P uptake
      by barley roots and wheat roots and resulted in significant (P </= 0.05) leakage
      of previously absorbed (32)P and total phosphorus (barley roots).
      Decenylsuccinate effects on (32)P uptake and retention were attributed to
      increased permeability resulting from injury. Decenylsuccinate at 10(-4) M did
      not inhibit root uptake of (32)P but decreased movement into the shoot. This
      could be interpreted as an indication of reduced transpiration or inhibition of
      (32)P loading into the transpiration stream. Decenylsuccinate did not increase
      cold hardiness in winter wheat in a nonhardening environment.

PMID- 16657271
TI  - Ribosomes during Development of Root Cells of Zea mays.

PMID- 16657272
TI  - Cytokinins in seeds of pumpkin.
AB  - Extracts of seeds of pumpkin (Cucurbita pepo Linn.) contain three
      chromatographically distinguishable cytokinins which are held on Dowex 50-W and
      are extractable by ethanol and n-butanol. Two of the active factors are
      precipitable by silver nitrate at acidic pH. The chromatographic behavior and the
      spectral characteristics of one of these cytokinins are similar to those of
      zeatin. However, the R(F) values of the other two active compounds do not match
      with those of any of the known natural cytokinins.

PMID- 16657273
TI  - The transportable auxin pool.
AB  - Evidences from experiments with stem sections of sunflower seedlings suggest that
      the transport of auxin may be limited by a restricted pool size of transportable
      auxin and restrictions in the availability of transport sites. A steady state of
      transport is observed over a range of lengths of stem sections, and over a wide
      range of auxin contents. The capacity of the sections to transport a pulse of
      auxin declines with aging after cutting, 50% decline occurring at about 10(+)
      hours; the transportability of a pulse of auxin declines rapidly after the
      completion of uptake, 50% decline occurring at about 1 hour. A chase treatment
      with unlabeled auxin does not alter transport, but a pretreatment with auxin
      depressed subsequent transport for about 1 hour. In depleted tissues such
      pretreatment is not inhibitory but rather is promotive of transport. The
      interpretation offered is that transport is limited by the pool size and
      transport sites, and roles for these factors are suggested in relation to the
      auxin transport gradient and the tropistic responses.

PMID- 16657274
TI  - Regulation of Bud Rest in Tubers of Potato, Solanum tuberosum L: VII. Effect of
      Abscisic and Gibberellic Acids on Nucleic Acid Synthesis in Excised Buds.
AB  - The effect of gibberellin A(3) (10(-4)m) and abscisic acid (10(-4)m), applied
      separately and together, on incorporation of (3)H-thymidine and (3)H-uridine into
      DNA and RNA of buds from freshly harvested potatoes was investigated. In some
      treatments apical buds in intact tubers were treated three times daily for 3 days
      with test solution before the buds were excised and treated an additional 12
      hours in Petri dishes. In other treatments, untreated buds were excised and
      treated 12 hours. Irrespective of length of treatment, gibberellin A(3) slightly
      promoted synthesis of DNA and RNA, and abscisic acid essentially blocked such
      synthesis, in both the presence and absence of gibberellin A(3).

PMID- 16657275
TI  - The effects of abscisic Acid on growth and nucleic Acid synthesis in excised
      embryonic bean axes.
AB  - Abscisic acid (ABA) is an effective inhibitor of cell elongation in excised
      embryonic bean axes whether added prior to or after the initiation of cell
      elongation. Zeatin partially reverses this growth inhibition. ABA inhibits (32)P
      incorporation into ribosomal RNA, transfer RNA, and DNA but not into the
      tenaciously bound fraction of elongating axes in a manner resembling 5
      fluorouracil, a compound which does not inhibit axis growth. The methylated
      albumin on kie-selguhr elution profiles of nucleic acids obtained from axes
      treated with either ABA, 5-fluorouracil, or a combination of the two are similar,
      and zeatin treatment has little apparent effect on these results. Our results
      suggest that the inhibition of growth in the axes by ABA is not due to its
      inhibition of DNA synthesis.ABA (1.9 x 10(-5)m) inhibits growth by 30 and 70%
      within 1 and 2 hours, respectively, after its addition to elongating axes. Its
      kinetics of inhibition are similar to those obtained with cycloheximide, and both
      compounds are more effective than 8-azaadenine. Based on these results, it is
      suggested that one possible effect of ABA may be at the level of translation.

PMID- 16657276
TI  - Metabolism of Inositol Phosphates: I. Phytase Synthesis during Germination in
      Cotyledons of Mung Beans, Phaseolus aureus.
AB  - The degradation of phytin in germinating mung bean seeds has been found to be
      associated with the increased activity of phytase in the cotyledon. In the
      differentiated embryo the increase of this activity is very low all throughout
      the growth periods studied. Phytase appears in the cotyledon during germination.
      No activity has been detected in the cotyledons of unsoaked seeds. Cycloheximide
      (10(-6) M) inhibits the appearance of phytase by 61% during 24 and 48 hours after
      the start of germination. This phytase increase is dependent on the synthesis of
      new RNA in the cotyledon. Synthesis of DNA is not detected in the cotyledon
      during germination.

PMID- 16657277
TI  - The Influence of Auxin and Ethylene on Chromatin-directed Ribonucleic Acid
      Synthesis in Soybean Hypocotyl.
AB  - Soybean seedlings treated with ethylene exhibited small increases in ribonucleic
      acid content in the elongating section of the hypocotyl. Chromatin isolated from
      the elongating section of ethylene-treated seedlings showed a 35 to 60% increase
      in the capacity for RNA synthesis. The ethylene-induced response was saturated at
      1 microliter/liter of ethylene and was fully expressed after 3 hours. Auxin
      caused marked accumulation of RNA and DNA in the elongating and basal tissue of
      the hypocotyl. Chromatin isolated from these auxin-treated tissues showed an 8-
      to 10- fold increase in RNA synthetic capacity as measured in vitro. Ethylene
      added with auxin reduced the auxin enhancement of nucleic acid synthesis in the
      elongating and basal tissues. Both ethylene and auxin treatment of the seedlings
      inhibited nucleic acid accumulation and chromatin activity in the apical tissue.
      Ethylene did not appear to mediate the auxin effects on nucleic acid synthesis in
      soybean hypocotyl with the possible exception of inhibition in the apical
      tissue.The RNA which was synthesized by chromatin isolated from control and auxin
      and ethylene-treated tissues was characterized by nearest neighbor analyses. The
      nearest neighbor frequencies of the RNA products synthesized by chromatin
      isolated from auxin- and ethylene-treated hypocotyl tissue were different from
      each other and different from the control RNA product.Seedlings treated in sealed
      containers exhibited growth, RNA, and DNA responses, especially to ethylene,
      different from those of seedlings treated in continuous flow containers.

PMID- 16657278
TI  - Metabolism and binding of C-maleic hydrazide.
AB  - Maleic hydrazide (MH) is taken up by corn and pea seedling roots and bound to
      some material which is insoluble in 80% ethanol or 5% trichloroacetic acid. (14)C
      MH is stable metabolically; chromatography of the 80% ethanol-soluble (14)C from
      treated corn roots and tobacco pith gives no indication of degradation. Very
      little (14)C-MH is bound in the zone of cell division (where MH acts to inhibit
      root elongation) or even in the region of cell enlargement in corn roots and most
      is bound 1 or more centimeters behind the tip. Likewise, very little MH is bound
      in corn coleoptile and tobacco pith sections. About 90% of (14)C-MH bound in corn
      roots is associated with large particles which may be cell wall fragments. The
      binding is blocked by azide and dinitrophenol, indicating a requirement for
      metabolic energy; however, inhibitors of protein synthesis (chloramphenicol,
      puromycin, cycloheximide) and DNA synthesis (fluorodeoxyuridine) do not inhibit
      binding. Only very small amounts of MH are bound in root homogenates, providing
      further evidence that the binding process is active. Once the MH is bound in the
      roots, the complex is stable for at least 1 week. Treatment with 2-aminoethanol
      releases MH.

PMID- 16657279
TI  - Comparative Studies on Plastoquinones: V. Changes in Lipophilic Chloroplast
      Quinones during Development.
AB  - Changes of lipophilic chloroplast quinones in corn, oats, peas, and Vicia faba
      are reported after 0, 4, 8, 12, 16, 20, 24, 48, 72, or 96 hours of exposure to
      light. There is a pronounced increase in plastoquinone A and chlorophyll levels
      and slight increase, in plastoquinone C(1-6), vitamin K(1), and alpha
      tocopherylquinone content. Coenzyme Q levels, on the other hand, show little
      change upon exposure to light.THE SEQUENCE IN WHICH INDIVIDUAL QUINONES APPEAR
      DURING DEVELOPMENT IS AS FOLLOWS: plastoquinone A instantaneously after exposure
      to light, plastoquinone C(1-6) from 4 to 24 hours, vitamin K(1) from 12 to 24
      hours, alpha-tocopherylquinone from 0 to 24 hours of illumination. Small amounts
      (<0.01 mumole/g, dry wt) of plastoquinone A and plastoquinone B are found in
      seeds and etiolated tissues. After exposure to light, the quinone tentatively
      identified as a member of the plastoquinone B series by reverse phase thin layer
      chromatography disappears and can be detected again in small amounts during
      maturity and toward senescence of the leaf.

PMID- 16657280
TI  - Radioactive gibberellin a(5) and its metabolism in dwarf peas.
AB  - Radioactive gibberellin A(5) ((3)H-GA(5)) was synthesized from gibberellic acid.
      When it was applied to dwarf peas grown in the dark, an average of 3% was
      converted to another acid gibberellin within 48 hours. The biological activity of
      the metabolite did not account for the response to applied GA(5). GA(5) is
      therefore assumed to be biologically active per se.(3)H-GA(5) did not appear to
      form a stable complex with a macromolecule in pea shoots. When injected into
      dwarf pea pods, (3)H-GA(5) was readily metabolized by maturing seed to more water
      soluble substances and to two other acidic compounds. This metabolism continued
      even throughout germination of the seed without reconversion of the metabolites
      to GA(5). It is concluded that "bound" GA(5) plays no part in the germination of
      dwarf pea seeds.

PMID- 16657281
TI  - Vesiculated Hairs: A Mechanism for Salt Tolerance in Atriplex halimus L.
AB  - The concentration of salts in the vesiculated hairs of Atriplex halimus L. was
      measured and was remarkably higher than that of the leaf sap and xylem exudate.
      In spite of their unusually high salt content, these hairs when immersed seemed
      unable to absorb water, in apparent contradiction to the previously held
      hypothesis that vesiculated hairs make it possible for such plants to absorb
      water from the atmosphere. Although growing the plants under saline conditions
      increased the salt content of the hairs from 2.3 m Na+K to 11.6 m, salt content
      of the expressed leaf sap from young leaves did not change significantly. This
      observation indicates that in A. halimus the vesiculated hairs play a significant
      role in removing salt from the remainder of the leaf and preventing the
      accumulation of toxic salts in the parenchyma and vascular tissues. Thus, a
      nearly constant salt content is maintained in leaf cells other than the hairs.

PMID- 16657282
TI  - Spectral similarities and kinetic differences of two tomato plant peroxidase
      isoenzymes.
AB  - The kinetic and spectral properties of peroxidases A and B from the dwarf tomato
      plant were compared. The absolute absorption spectra were essentially the same
      for peroxidases A and B and their derivatives. Peroxidases A and B had different
      pH optima with guaiacol as the hydrogen donor but essentially the same optimum
      when pyrogallol was the substrate. The substrate concentrations required for
      optimum activity were different not only for the different substrates but also
      for each isoenzyme. When pyrogallol was used as the substrate, peroxidases A and
      B were 80% active when assayed under conditions optimal for the other isoenzyme.
      When guaiacol was used as the substrate, peroxidase A was completely inactive
      when assayed under conditions optimal for peroxidase B. In this case the pH was
      not optimum and the H(2)O(2) concentration was inhibitory. Similarly, peroxidase
      B retained only 9% of its peroxidase activity toward guaiacol when assayed under
      conditions optimum for peroxidase A. In this case the pH was not optimum and the
      H(2)O(2) was limiting. A possible role for peroxidase isoenzymes is discussed.

PMID- 16657283
TI  - Regulation of Bud Rest in Tubers of Potato, Solanum tuberosum L: VI. Biochemical
      Changes Induced in Excised Potato Buds by Gibberellic Acid.
AB  - The rest period of the potato tuber was studied in relation to certain
      biochemical changes that are induced by gibberellic acid (GA(3)). The
      concentration of reducing sugars in excised plugs with buds treated with 10(-4)m
      GA(3) decreased in the first 4 hours after treatment and then rapidly increased
      up to 70 hours. The pattern in control buds was similar, but the changes occurred
      more slowly. The response to GA(3) is temperature-dependent and is not limited to
      any particular tissue of the tuber. The concentration of reducing sugars in
      excised buds increased proportionally to the log of the concentration of GA(3) in
      a range from 10(-8) to 10(-4)m. At 10(-3)m, GA(3) slightly inhibited production
      of reducing sugars. Malonate inhibits the initial decrease and the subsequent
      increase in reducing sugars in control buds, but not the increase induced by
      GA(3).Total protein in buds was not influenced by 10(-4)m GA(3) over a period of
      40 hours, nor did activity of alpha-amylase increase significantly until 20 hours
      after beginning of treatment. Invertase activity was present initially and, in
      the presence of GA(3), increased after 20 hours. GA(3) had no effect on starch
      phosphorylase activity, which was always present and remained steady over the 20
      hour test period.In short term experiments the rate of protein synthesis and
      synthesis of specific protein fractions were not affected by 10(-4)m GA(3), as
      measured by the incorporation of l-phenylalanine-U-(14)C or by experiments with
      (14)C- and (3)H- labeled l-phenylalanine or l-leucine.

PMID- 16657284
TI  - The aggregation States of phytochrome from etiolated rye and oat seedings.
AB  - Initial extracts from etiolated plants contained two aggregates of phytochrome. A
      major fraction was almost excluded by Sephadex G-200 and was within the
      fractionation range of Sepharose 4 B. A minor fraction was within the
      fractionation range of Sephadex G-200. Modifications of a previous isolation
      procedure which allowed retention of this aggregation state are reported. With
      respect to gel filtration, the major fraction of phytochrome from oat and rye
      seedlings was identical. The aggregates of rye and oat phytochrome were also
      separated by diethylaminoethyl cellulose chromatography.

PMID- 16657285
TI  - Effect of carbon dioxide, osmotic potential of nutrient solution, and light
      intensity on transpiration and resistance to flow of water in pepper plants.
AB  - The rate of transpiration, temperature of the leaves, and relative water content
      of leaves of pepper plants were measured in a small chamber in which the
      temperature, relative humidity, and carbon dioxide concentration of recirculated
      air were controlled and measured. The data reported were obtained by noting the
      response of pepper plants to all combinations of the following treatments: high
      light, 1.5 x 10(6) ergs per square centimeter per second; low light, 3.0 x 10(4)
      ergs per square centimeter per second; three levels of CO(2): 50, 268, and 730
      parts per million; nutrient solution osmotic potentials of -0.5, -5.0, -7.5, and 
      9.5 bars.The rate of transpiration of pepper plants was reduced by a decrease in
      osmotic potential of the nutrient solution, an increase in CO(2) concentration in
      the ambient air, and a decrease in light intensity. The response, as measured by
      transpiration, to the three variables, light, CO(2), and osmotic potential
      indicated that each variable influenced a different and independent mechanism. A
      change in a single variable produced essentially the same percentage change at
      all levels of the other variables. The rate of movement of water from roots to
      leaves was in response to water potential gradient and not the actual potential
      in the leaves.The resistance to flow of water through the plants (R) was
      estimated by dividing the difference between the water potentials of the solution
      and the leaves by the rate of transpiration. The data indicated an increase in R
      as the rate of transpiration decreased. The type and size of errors encountered
      in the estimation of R and location of R within the plant are discussed.

PMID- 16657286
TI  - Kinetics of C-14 translocation in soybean: I. Kinetics in the stem.
AB  - A kinetic study was made of the translocation of (14)C-photosynthate through
      soybean stems following pulse labeling and during steady state labeling of the
      first trifoliolate leaf. The translocation profile proceeded down the stem with
      little or no change in shape. Following pulse labeling, sucrose accounted for 90
      to 95% of the radioactivity in the stem at all times up to 2 hours, at which time
      less than 3% of the activity was in an insoluble form. Kinetic data on the
      relative specific activities of sucrose in the leaf and petiole indicated that
      two-thirds of the petiolar sucrose was in the translocation stream and the
      remaining one-third was in a stationary pool which slowly accumulated sucrose
      from the translocation stream. With this assumption, the rate of sucrose efflux
      from the leaf was calculated to be 22 micrograms per minute, which was equivalent
      to a sucrose mass flux in the sieve tubes of 20 grams per square centimeter per
      hour.It is concluded that translocation proceeded without a net radial velocity
      distribution and with slight loss of translocate, mainly as sucrose, from the
      translocation stream. The kinetics of (14)C translocation must, therefore, be
      determined primarily by factors operating within the leaf rather than in the
      stem. One of these factors may be the presence in the soybean leaf of a
      specialized paraveinal mesophyll. Since there was no spreading of the profile,
      the results were inconsistent with an "active diffusion" mechanism of
      translocation (i.e., a mechanism describable by diffusion equations). The data
      and conclusions are in substantial agreement with those of Moorby, Ebert, and
      Evans.

PMID- 16657287
TI  - Kinetics of C-14 Translocation in Soybean: II. Kinetics in the Leaf.
AB  - The kinetics of (14)C-assimilates in the soybean leaf were studied in pulse
      labeling and steady state labeling experiments. (14)C-Sucrose apparently served
      as the ultimate source, at least, of translocated (14)C-sucrose. However, since
      the specific activity of leaf sucrose reached a maximum within 5 minutes after
      pulse labeling, whereas that of exported sucrose did not reach a maximum until at
      least 20 minutes, it appeared that there were two sucrose compartments in the
      leaf. A possible physical basis for the two compartments may be the mesophyll (a
      photosynthetic compartment) and a specialized "paraveinal mesophyll" (a
      nonphotosynthetic compartment), through which photosynthate must pass on its way
      to the veins.The (14)C kinetics of sterol glucoside, and probably esterified
      sterol glucoside, were similar to those for (14)C-sucrose export. Sterol
      glucoside was labeled only in its glucose moiety and was the only stem lipid
      which became strongly labeled during (14)C-sucrose translocation. These sterol
      derivatives may act as membrane carriers of sucrose between the translocation
      stream and surrounding cells.The kinetics of (14)C-sucrose and its movement to
      the veins are discussed with reference to compartmentation within the leaf and
      metabolic exchange with other compounds, particularly with starch. Although a
      simple compartmental model gave a fairly accurate description of (14)C-sucrose
      kinetics, an entirely accurate model could not be provided, primarily because of
      loss of (14)C from sucrose, at an unknown rate, to starch.

PMID- 16657288
TI  - Kinetics of C-14 Translocation in Soybean: III. Theoretical Considerations.
AB  - Based largely on data from soybean, some mathematical models are derived to
      describe the transport kinetics of (14)C-photosynthate. The effects of leaf size,
      leaf shape, and translocation velocity on the rate of tracer efflux from the leaf
      are considered, and it is shown that the duration of these effects will
      approximate the time required for tracer to reach the petiole from the farthest
      point of the leaf. This duration is designated as the "kinetic size" of the leaf.
      Although its effect will be slight in the case of soybean (about 2 to 3 minutes),
      a considerable effect of the kinetic size will be found in the case of large
      leaves, or when the translocation velocity is low.Source pool kinetics in soybean
      are described by a two-compartment model, one compartment representing a
      photosynthetic compartment and the second (the source pool) a nonphotosynthetic
      compartment next to the veins. The kinetics in the petiole are approximated by a
      two-compartment model representing the translocation stream and tissues outside
      the translocation stream. A combination of the models predicts fairly accurately
      the translocation kinetics observed in soybean.The models are compared with
      others in the literature. Although the assumptions are in substantial agreement
      with those made by Evans, Ebert, and Moorby, they are inconsistent with the model
      based on the movement of transcellular strands presented by Canny and Phillips.

PMID- 16657289
TI  - Diffusion and osmotic transfer in corn mitochondria.
AB  - An equation based on the assumption of solute diffusion into an expanding sink is
      derived and describes the passive swelling of corn shoot (Zea mays L.)
      mitochondria. The experimental data show that corn mitochondria not only swell
      due to diffusive forces but also contract according to osmotic phenomena,
      provided sufficient impermeant solute is included to prevent lysis.

PMID- 16657290
TI  - Active and passive transport of potassium in cells of excised pea epicotyls.
AB  - The Ussing-Theorell equation, which provides a fundamental test for the
      independent passive movement of ions under conditions of nonequilibrium, has been
      used to assess the active and passive components of K(+) uptake by segments of
      pea epicotyl (Pisum sativum L. cultivar Alaska), incubated for 24 hours in both 1
      fold and 10-fold concentrations of a complete nutrient solution. Measurements of
      the rates at which (42)K diffused out of the segments provided data from which
      were estimated the K(+) content of, and the fluxes to and from, the nonfree space
      compartments, interpreted as being cytoplasm and vacuole. For this analysis the
      serial model of MacRobbie and Dainty and Pitman for the spatial arrangement of
      cell compartments was used. On the basis of these values, and measurements of
      electrical potential across the cell membranes, the vacuolar K(+) concentration
      was found to be fairly close to that expected as a result of passive diffusion
      between the cytoplasm and vacuole provided that no potential exists across the
      tonoplast. Cytoplasmic K(+) concentration, however, was much too high in both
      treatments to be accounted for in passive terms. It was concluded, therefore,
      that, on the basis of the model, the high ratio of influx to efflux was
      maintained in the cells by an active K(+) pump located at the plasmalemma. There
      is some reason to question the applicability of this model for flux analysis to
      the conditions of high net influx as encountered here; nonetheless, it provides a
      first approach to an over-all flux analysis in pea stem tissue.

PMID- 16657291
TI  - Some observations on the carbon dioxide burst in chlorella and chlamydomonas.
AB  - In the course of mass spectrometer studies with the algae Chlorella and
      Chlamydomonas, data were obtained which indicate that the CO(2) burst and gulp
      are sensitive to oxygen. Furthermore, the CO(2) burst was found to be strongly
      suppressed when wave lengths shorter than 460 nanometers were blocked at
      intensities adequate to saturate photosynthesis. Under appropriate conditions at
      30 degrees , the CO(2) burst was interrupted by a brief CO(2) gulp and the post
      illumination gulp by a brief burst of CO(2). The post illumination gulp of CO(2)
      could be induced during illumination by interposition of a filter blocking wave
      lengths shorter than 460 nanometers. These data are discussed in relation to
      earlier reports of the phenomenon and briefly as they affect the detection of
      photorespiration.

PMID- 16657292
TI  - Timing of the auxin response in etiolated pea stem sections.
AB  - The short term growth response of etiolated pea stem segments (Pisum sativum L.,
      var. Alaska) was investigated with the use of a high resolution growth-recording
      device. The immediate effect of treatment with indole-3-acetic acid is an
      inhibition of growth. This inhibition lasts about 10 minutes, and then the rate
      of elongation rises abruptly to a new steady rate about 4 times the rate of
      elongation before auxin treatment. This rapid steady rate of elongation, however,
      continues for only about 25 minutes before declining suddenly to a lower steady
      rate of growth about 2 times the rate of elongation before the addition of auxin.
      Pretreatment of the segments with cycloheximide or actinomycin strongly inhibits
      both phases of auxin-promoted elongation without altering the length of the
      latent period in response to the hormone.

PMID- 16657293
TI  - Deuterium oxide as a density label of peroxidases in germinating barley embryos.
AB  - Density labeling with deuterium oxide, gel electrophoresis, and isopycnic
      equilibrium sedimentation were used to study the appearance and disappearance of
      individual peroxidases in the embryos of germinating barley. No detectable label
      was incorporated into those peroxidases which are present in the embryo of the
      dry seed and disappear during germination. Deuterium was incorporated into the
      additional peroxidases which appeared in the embryo during germination. This
      incorporation is not due to deuterium-hydrogen exchange into preformed proteins.
      The results indicate that the newly appearing peroxidases arise by synthesis
      during germination.

PMID- 16657294
TI  - The Mechanism of Hydrogen Evolution by Chlamydomonas moewusii.
AB  - Using manometric techniques, H(2) evolution in both darkness and light has been
      studied in the green alga, Chlamydomonas moewusii.Hydrogen evolution in the dark
      is accompanied by the release of only CO(2) in manometrically detectable amounts.
      It is depressed by dark starvation and inhibited both by monofluoroacetic acid
      and by uncouplers of phosphorylation. This evidence suggests that the reaction is
      dependent on oxidative carbon metabolism for reductant and phosphorylation for
      energy to raise the reductant to a redox potential capable of reducing
      H(+).Photoevolution of H(2) is also accompanied by the release of only CO(2). It
      is depressed by dark starvation and stimulated by acetate or a period of
      photosynthesis. Monofluoroacetic acid causes complete inhibition, while 3-(3,4
      dichlorophenyl)-1,1-dimethylurea causes no or only slight inhibition. These
      results indicate that oxidative carbon metabolism is the source of reductant for
      the reaction. Photoevolution of H(2) does not show Emerson enhancement, and it
      has an action spectrum peaking at a longer wave length than that of
      photosynthesis. These characteristics, together with the slight effect of 3-(3,4
      dichlorophenyl)-1,1-dimethylurea on the reaction, show that only system I of
      photosynthetic electron transport is involved in the reaction. Photoevolution of
      H(2) is stimulated by uncouplers; this indicates that the role of light is not to
      provide energy by phosphorylation. Rather, the results support an electron flow
      driven directly by light through system I from reductant produced in oxidative
      carbon metabolism to a redox potential capable of reducing H(+).

PMID- 16657295
TI  - Grafting and gibberellin effects on the growth of tall and dwarf peas.
AB  - Tall peas var. Alaska and dwarf peas var. Progress No. 9 were grafted onto their
      own roots or reciprocally grafted to determine the rootstock effect on the growth
      of the stem. In all cases the grafted stems grew the same as their ungrafted
      controls regardless of which rootstock they were grown on. When similarly grafted
      plants were supplied with gibberellic acid, good graft unions did not inhibit its
      translocation. This evidence supports the thesis that the mechanism controlling
      stem growth in peas is located in the stem and that the roots have no direct
      control over this mechanism.

PMID- 16657296
TI  - Starch Synthesis Studies in Zea mays: II. Molecular Distribution of Radioactivity
      in Starch.
AB  - The amylose and amylopectin fractions from kernel starch synthesized shortly
      after exposure of intact Zea mays L. plants to (14)CO(2) had similar specific
      radioactivities (counts per min per mg of carbohydrate). In both fractions the
      radioactivity was distributed throughout the molecules. These data are consistent
      with a model in which the polysaccharides are synthesized in the matrix of the
      amyloplast followed by crystallization of the completed molecules onto the starch
      granule.

PMID- 16657297
TI  - Adenosine Triphosphatase Activities in Leaves of the Mangrove Avicennia nitida
      Jacq: Influence of Sodium to Potassium Ratios and Salt Concentrations.
AB  - Homogenates from the salt-excreting leaves of the mangrove Avicennia nitida were
      subjected to differential centrifugation and investigated for adenosine
      triphosphatase activities. At pH 6.75 a salt stimulation with peaks at three
      different sodium to potassium ratios could be demonstrated above the activity due
      to Mg(2+) ions. The stimulation by sodium and potassium depends on the ionic
      strength of the test medium, higher salt concentrations being inhibitory. The
      plant system seems thus more complicated than the animal activities. Technically,
      this means that a search for (Na(+) + K(+))-activated ATPases in plants should be
      performed with a close spacing of Na:K ratios at several constant levels of salt.
      Literature data on the transport of Na(+) and K(+) indicate that the
      physiological situation is rather complex in plants.

PMID- 16657298
TI  - The effect of water stress on mitochondria of root cells: a biochemical and
      cytochemical study.
AB  - Water loss from root cells of Zea mays induced by exposure to severe water
      stress, caused a reduction in the respiratory rate (O(2) consumption) and at the
      same time an increase in activity of the mitochondrial cytochrome oxidase
      (histochemical oxidation of diaminobenzidine). The connections between these
      changes and the changes in the fine structure of the mitochondria occuring in the
      stressed roots are discussed.

PMID- 16657299
TI  - Effect of Oxygen on the Light-enhanced Dark Carbon Dioxide Fixation in Chlorella
      Cells.
AB  - With Chlorella ellipsoidea cells, the effect of oxygen was investigated on the
      products of enhanced dark (14)CO(2) fixation immediately following
      preillumination in the absence of CO(2). When the reaction mixture was made
      aerobic by bubbling air (CO(2)-free) throughout preillumination and the following
      dark (14)CO(2) fixation periods, the initial fixation product was mainly 3
      phosphoglyceric acid. When nitrogen gas had been used instead of air, only about
      one-half of the total radioactivity in the initial fixation products was in 3
      phosphoglyceric acid and the rest in aspartic, phosphoenolpyruvic, and malic
      acids. The percentage distribution of radioactivity incorporated in these initial
      products rapidly decreased during the rest of the dark period. Concurrent with
      the decrease in the initial (14)CO(2) fixation products, some increase was
      observed in the radioactivities of the sugar phosphates. The maximal
      radioactivity incorporated in sugar mono- and diphosphates accounted for only 10%
      of total (14)C, under either the aerobic or anaerobic conditions. Under anaerobic
      conditions most of the (14)C incorporated was eventually transferred to alanine,
      whereas the main end products under aerobic conditions were aspartate and
      glutamate. The pattern of (14)CO(2) fixation products was unaffected by the
      atmospheric condition during the period of preillumination. The preferential flow
      of the fixed carbon atom to alanine or aspartate depended on the presence or
      absence of oxygen during the period of dark CO(2) fixation.

PMID- 16657300
TI  - Effect of Potassium Deficiency upon Translocation of C in Detached Blades of
      Sugarcane.
AB  - The translocation of radioactive photosynthate was studied in blades detached
      from plants which had been grown in nutrient solution with and without potassium.
      Basipetal translocation decreased in the blades of plants deprived of potassium,
      even when deficiency symptoms were not visible. In such slightly potassium
      deficient leaves, translocation was decreased in the light but not in the dark.
      More severe potassium deficiency decreased translocation both in darkness and in
      light. Potassium deficiency decreased translocation at light intensities giving
      no difference in rate of photosynthesis between plus and minus potassium leaves
      and even at light intensities at which there was no net fixation of carbon
      dioxide. At all levels of deficiency, the relative decrease in translocation was
      greater than the relative decrease in photosynthesis. Translocation was affected
      at potassium deficiency levels which had no effect upon photosynthesis.Potassium
      deficiency decreased translocation relatively more than it decreased moisture
      content. There was a much better correlation between the decrease in potassium
      and translocation than between the decrease in moisture and translocation.An
      experiment with radioactive phosphorus indicated an upset in phosphorylation in
      the stems of potassium-deficient plants.

PMID- 16657301
TI  - Dipyridyl-induced Cell Elongation and Inhibition of Cell Wall Hydroxyproline
      Biosynthesis.
AB  - Incubation of soybean hypocotyl sections with 0.1 millimolar 2,2'-dipyridyl in
      the absence of auxin results in increases in growth rate and in cell wall
      extensibility lasting for about 3 hours. This is accompanied by greatly decreased
      biosynthesis of hydroxyproline, which ultimately appears in the wall, and in
      slightly reduced oxygen uptake, both of which continue for at least 9 hours.
      Continuous synthesis of hydroxyproline which appears in the cell wall is thus not
      necessary for short term growth. The decrease in growth and cell wall
      extensibility that occurs between the 3rd and 9th hours of dipyridyl inhibition
      cannot be attributed to cross-linking of newly synthesized hydroxyproline, since
      its synthesis is still inhibited.

PMID- 16657302
TI  - Regulation of root growth by auxin-ethylene interaction.
AB  - A large portion of indoleacetic acid (IAA)-induced inhibition of excised root
      tips and virtually all such inhibition of intact roots are the result of IAA
      dependent ethylene production. Under certain conditions an additional effect of
      IAA accounts for a small portion of the inhibition of excised root tips. Ethylene
      production in response to applied IAA is governed by the level of applied auxin
      found inside the root. Evidence is presented to confirm the participation of
      ethylene in the geotropic response of roots.

PMID- 16657303
TI  - Rapid regeneration of protochlorophyllide(650).
AB  - The rate of regeneration of protochlorophyllide(650) was examined
      spectrophotometrically after a saturating light flash using 8- to 9-day-old dark
      grown bean leaves. The regeneration occurred to the extent of 15% with a half
      rise time of about 20 seconds. Feeding delta-aminolevulinic acid to the excised
      leaves in the dark increased protochlorophyllides(635) but not the absorption at
      650 nanometers, suggesting that the holochrome was normally saturated with
      protochlorophyllide and that the holochrome protein was not controlled by the
      level of protochlorophyllide. After a light flash, the excess
      protochlorophyllide, formed from exogenous delta-aminolevulinic acid, readily
      combined to regenerate the 650 nanometer absorbing species; the regeneration
      occurred to the extent of 60 to 80% with a half rise time of about 50 seconds.
      Regeneration was blocked at 0 degrees , suggesting that there was some enzymic
      process required for regeneration, possibly the formation of a reductant
      component of the protochlorophyllides(650) holochrome.

PMID- 16657304
TI  - Effects of growth substances on the absorption and transport of iron plants.
AB  - The effects of a number of growth substances on the absorption and translocation
      of iron were studied in bean plants. Gibberellic acid application to the
      trifoliate leaf enhanced absorption of Fe applied to the primary leaf. 2
      Chloroethyltrimethylammonium chloride increased absorption by the primary leaf
      while 6-furfurylaminopurine (kinetin) increased the transport of Fe from the
      primary leaf to other parts. When the roots were pretreated with gibberellic
      acid, the absorption of Fe by the primary leaf and subsequent transport to the
      trifoliate leaves were increased. Triiodobenzoic acid reduced the absorption and
      transport of Fe.Absorption of Fe by roots and transport to other parts were
      increased by pretreatment of the roots with gibberellic acid, 2
      chloroethyltrimethylammonium chloride or N,N-dimethylaminosuccinamic acid for 3
      days. An increase in the transport to other parts of Fe absorbed by roots was
      obtained when roots were exposed to the growth substances following Fe
      absorption.Absorption and transport of Fe in corn plants were much less than
      those of Rb and phosphate. Absorption and transport of Fe were greater in plants
      with decorticated roots than in those with intact roots. N,N
      Dimethylaminosuccinamic acid significantly promoted the transport of root
      absorbed Fe to the shoots of corn plants.

PMID- 16657305
TI  - An Autoinhibitory Substance Produced by Platydorina caudata Kofoid.
AB  - An inhibitory substance was obtained from culture filtrates of Platydorina
      caudata Kofoid, (a colonial, green flagellate), in which death of the culture had
      occurred. The cessation of growth occurs before, and is seemingly independent of,
      medium depletion. The substance can be detected as early as the 15th day, and by
      the 25th day growth is completely suppressed. A bioassay method for quantitating
      the activity of the substance was devised. The substance is heat-labile,
      nondialyzable, acid-labile, and apparently specific for Platydorina. The
      substance resists short periods of freezing and bacterial contamination.
      Preliminary results suggest that trypsin destroys activity of the substance.

PMID- 16657306
TI  - A monophenol oxidase activity in extracts of sorghum.
AB  - A p-hydroxycinnamic acid oxidase activity was present in enzyme preparations from
      first internodes of Sorghum vulgare variety Wheatland milo when incubated in
      phosphate buffer at pH 7.5. This preparation had no classical polyphenolase
      activity but had both peroxidase and catalase activities. Since horseradish
      preparations catalyzed the same reaction, the oxidation probably is another
      example of a peroxidase-oxidase reaction. A second substrate was p
      hydroxyphenylpyruvic acid. Ferulic acid was slightly active at low concentrations
      and inhibitory at higher ones. Diphenols such as caffeic and chlorogenic acids
      were inactive and inhibitory to p-hydroxycinnamic acid oxidation. A variety of
      monophenols such as tyrosine and cinnamic acid were inactive. An active substrate
      must have a free monophenolic group and para to this a C(3) side chain with a
      double bond and probably a free terminal acid group. A sulfhydryl reducing agent
      at the 5 millimolar level such as mercaptoethanol, reduced glutathione, or
      dithiothreitol was obligatory. Products were varied and were found in both the
      ethyl acetate-soluble and insoluble fractions after acidification of the
      incubation mixtures. With internode extracts, about 1 micromole of O(2) was
      consumed per micromole of p-hydroxycinnamic acid that disappeared in the presence
      of mercaptoethanol. Tetrahydrafolic acid plus mercaptoethanol were required for a
      second step oxidation or a parallel reaction; about 2 micromoles of O(2) were
      consumed per micromole of p-hydroxycinnamic acid that disappeared. Potassium
      cyanide, diethyldithiocarbamate, ascorbic acid, and ethylenediaminetetraacetate
      were inhibitory. A similar mercaptoethanol-dependent monophenol oxidase was
      present in preparations from green shoots that also contained a classical
      polyphenolase activity. The activity was present in both soluble and particulate
      (500 to 100,000 gravity) fractions of internodes. Preliminary studies were made
      of enzyme complexes in the particulate fractions capable of converting
      phenylalanine and tyrosine to the level of ferulic acid when the above p
      hydroxycinnamic acid oxidase was blocked with ascorbic acid. The ratelimiting
      step was the hydroxylation of p-hydroxycinnamic acid.

PMID- 16657307
TI  - Synthesis and Secretion of Hydroxyproline-containing Macromolecules in Carrots:
      II. In vivo Conversion of Peptidyl Proline to Peptidyl Hydroxyproline.
AB  - The chelator alpha,alpha'-dipyridyl prevents the formation of protein-bound
      hydroxyproline without affecting protein synthesis as measured by the
      incorporation of (14)C-proline. The inhibitory effect can be overcome by
      exogenous ferrous ions. Neither alpha,alpha'-dipyridyl nor Fe(2+) interferes in
      any other known way with the synthesis and secretion of the hydroxyproline-rich
      proteins normally found in the cell wall. This reversal by Fe(2+) of the
      inhibition of proline hydroxylation by alpha,alpha'-dipyridyl is used for a study
      in vivo of the hydroxylation reaction. This reaction has a temperature
      coefficient of 2.2, suggesting that it is an enzymatic process. Reversal by
      Fe(2+) of the alpha,alpha'-dipyridyl inhibition can occur after protein synthesis
      has been arrested with cycloheximide, indicating that peptidyl proline is the
      substrate of the hydroxylation reaction. Hydroxylation occurs in the cytoplasm,
      and not in the cell wall, and only for a limited time after the incorporation of
      proline into the polypeptide chain. This suggests a spatial separation of the
      enzyme and the substrate.

PMID- 16657308
TI  - Inhibition of the beta-Carboxylation Pathway of CO(2) Fixation by Bisulfite
      Compounds.

PMID- 16657309
TI  - Rotation axes for clinostat studies in light.

PMID- 16657310
TI  - Determination of Linkages of beta-d-Glucans from Lupinus albus and Avena sativa
      by exo-beta-(1 --> 3)-d-Glucanase.

PMID- 16657311
TI  - Photoreactions Controlling Flowering of Chrysanthemum morifolium (Ramat. and
      Hemfl.) Illuminated with Fluorescent Lamps.
AB  - Flowering of chrysanthemum plants under short photoperiods, as is well known, is
      prevented when the plants are illuminated near the middle of the long night. Such
      illumination inhibits flowering whether it is given continuously or
      intermittently, and whether it comes from incandescent or from fluorescent lamps.
      We discovered, however, that fluorescent light applied intermittently
      (cyclically) throughout the entire 16-hour long night was far less inhibitory
      than when applied during only part of this dark period. By contrast, incandescent
      filament illumination is strongly inhibitory under these conditions. The cycles
      of fluorescent light usually lasted 15 minutes, 1.5 minutes of light followed by
      13.5 minutes of dark. When such cycles were applied for only 12 hours, leaving 4
      hours of uninterrupted darkness in each long night, inhibition of flowering was
      complete again.

PMID- 16657312
TI  - Physiology of oil seeds: I. Regulation of dormancy in virginia-type peanut seeds.
AB  - The germination and ethylene production by dormant Virginia-type peanut seeds
      were observed in relation to phytohormone treatments that could conceivably
      release the dormancy of these seeds. A comparison was made between the effects of
      these treatments on the less dormant apical seeds and the more dormant basal
      seeds. Indole-3-acetic acid did not stimulate ethylene production by, or
      germination of, the dormant seeds to any extent. Gibberellic acid at 5 x 10(-4) M
      stimulated ethylene production by apical seeds to 17 millimicroliters per hour
      and germination to only 40% above the control. The more dormant basal seeds were
      affected even less by gibberellic acid than the seeds. Ethylene gas at 8
      microliters per liter stimulated germination to 85% above the control for both
      apical and basal seeds. At this ethylene concentration the physiology of the more
      dormant basal seeds was altered, so that they behaved in a manner similar to the
      inherently less dormant apical seeds. 2-Chloroethylphosphonic acid at 10(-3) and
      5 x 10(-4) M provided results similar to ethylene gas. Both apical and basal
      seeds germinated 100% at 48 hours. Among the phytohormones tested in this study,
      ethylene gas produced the greatest germination at low concentrations, and it
      appears must directly related to initiating the reactions required for converting
      the quiescent cells to an active state of growth.

PMID- 16657313
TI  - Translocation of iron citrate and phosphorus in xylem exudate of soybean.
AB  - Soybean plants, Glycine max (L.) Merrill, in standard solution received 2.5 mum
      ferric ethylenediamine di(o-hydroxyphenylacetate (FeEDDHA) and 0 to 128 mum
      phosphorus. Their stem exudates contained: 32 to 52 mum Fe, 120 to 5000 mum P,
      and 120 to 165 mum citrate. Electrophoresis of exudates with high P caused Fe
      trailing that precluded identification of any major form of Fe. Exudate with low
      P gave an anodic band of Fe citrate as the major Fe compound. Phosphate added to
      exudate in vitro depressed the Fe citrate peak and cause Fe trailing. EDDHA added
      to exudate in vitro pulled Fe from Fe citrate; citrate then migrated as a slower
      form and Fe migrated as FeEDDHA. A modified preculture system, involving 2-day
      renewals of 0.2 mum FeEDDHA with 3.2, 9.6, or 16 mum P and low levels of other
      ions, controlled pH depression and produced considerable change in citrate and P
      levels. The exudates contained: 45 to 57 mum Fe, 200 to 925 mum P, and 340 to
      1025 mum citrate. The high citrate was from plants grown with low P. The major
      form of Fe in the exudates was Fe citrate. This is probably the form translocated
      in the plants.

PMID- 16657314
TI  - Mobilization and Incorporation of Photoassimilated C by Growing Vegetative and
      Reproductive Tissues of Adult Pinus resinosa Ait. Trees.
AB  - Variations in translocation and incorporation of (14)C-labeled photosynthate in
      actively growing vegetative and reproductive tissues of 20-year-old Pinus
      resinosa trees with time were investigated. Five hours after exposure of 1-year
      old needles on second order branches to (14)CO(2), 90% of the recoverable
      activity was still in the needles. The 1-year-old bark showed a small amount of
      activity, but terminal sinks had accumulated little (14)C. After 24 hours,
      activity in the 1-year-old needles decreased to 59% while actively growing
      terminal and lateral shoots and 2nd year cones had accumulated considerable
      tracer. Whereas activity in the 1-year-old bark increased, recovery from the 1
      year-old wood was only 1.8%. After 1 week, relative activity in the 1-year-old
      needles had declined to 27%. Recovery of (14)C from various sinks was high and in
      the following order: 2nd year cones > terminal needles > lateral needles >
      terminal internode > lateral internodes > 1-year-old wood. Ninety per cent of the
      (14)C recovered after 5 hours was in the ethanol-soluble form, but by the end of
      1 week only half was in the soluble fraction. Incorporation of tracer into
      insoluble compounds was high in expanding internodes and in 1-year-old xylem, and
      low in 2nd year cones. Total activity in the terminal internode generally
      declined toward the distal end while specific radioactivity increased. Only 5% of
      the (14)C recovered from cones was localized in developing seeds, but specific
      radioactivity of seeds was higher than in the cone scales and axis.

PMID- 16657315
TI  - Effect of cycloheximide, gamma irradiation, and phosphorus deficiency on root
      pressure exudation in tobacco.
AB  - Cycloheximide drastically reduced the rate of root pressure exudation in detopped
      tobacco (Nicotiana tabacum L.), and the effect was more pronounced for nitrate
      salts in the external solution than for some other salts or when the roots were
      in water. Diurnal periodicity was greatly decreased, and its phase was changed.
      Effects began within an hour. Cation uptake was reduced by relatively low levels
      of cycloheximide. The effects of cycloheximide seemed to be reversible. Mild
      phosphorus deficiency resulted in decreased exudation rates from detopped tobacco
      and in no response to nitrate. Periodicity of exudation was not greatly affected
      by phosphorus deficiency, however. Gamma ray irradiation with a (60)Co source at
      levels (up to 40-50 kiloroentgens) which are considered disruptive of moderately
      large molecules had relatively little effect on the exudation rate. Higher levels
      of irradiation, which disrupt most protein molecules, decreased exudation and
      obscured periodicity. The results indicate either that new protein (or peptide)
      synthesis is needed for the rapid nitrate transport or that the deficiency and
      inhibitor disrupt cellular membranes. Phosphorus deficiency increased the
      sensitivity of the plants to inhibition by irradiation of the exudation process.

PMID- 16657316
TI  - Growth Regulator Changes in Cotton Associated with Defoliation Caused by
      Verticillium albo-atrum.
AB  - Cotton plants, variety Acala 4-42 family 77 (Gossypium hirsutum L.,), were stem
      puncture-inoculated with either a defoliating isolate (T9) or a nondefoliating
      isolate (SS4) of Verticillium albo-atrum (Reinke and Berth.). As symptoms
      developed, growth regulators were assayed in diseased plants to discern their
      importance in the disease syndrome.An Avena coleoptile straight growth bioassay
      demonstrated the presence of several growth-regulatory compounds in cotton tissue
      extracts. Indoleacetic acid was among the compounds whose effects on coleoptile
      growth were influenced by disease development. Coleoptile growth due to
      indoleacetic acid was greater in extracts of diseased stems and leaves than in
      extracts of comparable healthy tissues. During the defoliation period the T9 and
      SS4 isolates appeared equally effective in increasing indoleacetic acid and
      reducing indoleacetic acid decarboxylation. Preceding defoliation, however, in
      plants showing equivalent symptoms the degradation of auxin was reduced more by
      infection with T9, the defoliating isolate. The reduced auxin degradation
      appeared to be releated to concomitant increases in caffeic acid and other
      indoleacetic acid-oxidase inhibitors in the affected tissues.Abscisic acid in
      tissue extracts strongly inhibited coleoptile growth. During the defoliation
      period gas-liquid chromatographic and ultraviolet absorption measurements
      revealed that abscisic acid levels were approximately doubled in T9-infected
      leaves but were relatively unaffected in leaves infected with the nondefoliating
      isolate and in stems infected with either isolate.The onset of epinasty and
      especially defoliation was also accompanied by increased ethylene production in
      diseased plants. Ethylene in gas samples taken from jars confining plants
      infected with SS4 or T9, respectively, was increased 2- and 5-fold over
      uninoculated controls. Ethylene supplied exogenously to healthy plants in
      concentrations as low as 0.2 microliter per liter induced both the epinasty and
      defoliation symptoms characteristic of Verticillium infection. Ethylene treatment
      did not, however, induce other symptoms of Verticillium infection and did not
      affect endogenous levels of abscisic acid.Defoliation of T9-but not SS4-infected
      plants apparently is related to the differential alterations in abscisic acid and
      ethylene levels induced by each isolate, and perhaps to differential alterations
      in initial rates of indoleacetic acid decarboxylation. These growth regulator
      alterations apparently are reflections of altered host metabolism rather than
      direct contributions of the invading fungus.

PMID- 16657317
TI  - Interaction between Antheridogens and Fatty Acids in Fern Spore Germination.
AB  - Certain fatty acids in the C(5) to C(18) range, at concentrations as low as 10(
      5) M, were found to inhibit the germinations of spores of the sensitive fern,
      Onoclea sensibilis L. The addition of gametophytic culture flltrates of the
      bracken fern, Pteridium aquilinum (L.) Kuhn, containing antheridogen A, was found
      to overcome this inhibition and allow the spores to germinate and the
      gametophytes to develop in a normal fashion. Some fatty acids were found to
      increase the antheridium-inducing potency of antheridogen A as much as 10-fold.
      An effect similar to this may promote the diecious reproduction of ferns.

PMID- 16657318
TI  - Promotion and inhibition of iron accumulation in soybean plants.
AB  - Plants of four soybean (Glycine max L. Merrill) genotypes differing in their
      ability to accumulate iron were studied. The efficient genotypes were Hawkeye
      (HA) and A62-9 (E-9), and the inefficient ones were PI-54619-5-1 (PI) and A62-10
      (I-10). When plants of opposite efficiency were grown in the same solution, iron
      accumulation decreased in the primary leaves of efficient plants, but it was
      unaffected or slightly reduced in the leaves of inefficient plants.Absorption of
      iron during a 24-hour period by 17-day-old plants indicated that solutions in
      which either HA or PI plants had been previously cultured contained a heat-labile
      factor which increased iron accumulation by iron-stressed HA plants. Also, it was
      found that HA plants from mixed culture accumulated about 50% less iron than HA
      plants grown in pure culture, independent of the absorption solution used. The
      conditions described, therefore, may either stimulate or inhibit iron
      accumulation in efficient soybean plants.

PMID- 16657319
TI  - Respiratory Response, Ethylene Production, and Response to Ethylene of Citrus
      Fruit during Ontogeny.
AB  - The initial respiratory rates at 20 centrigrade of detached oranges (Valencia and
      navel), grapefruit, and lemons decreased during ontogeny. Small attached oranges
      respired at the same rate as detached fruits of the same weight, and cutting the
      pedicel produced no shock or injury stimulus to the respiratory rate. Small
      oranges and grapefruit (average weight about 15 grams) showed pseudoclimacteric
      respiratory patterns and produced ethylene. The height of the respiratory rise
      and the amount of ethylene produced decreased as the fruit increased in weight
      until the September 4th harvest, when the fruit weights were 120, 64, and 87
      grams for grapefruit, Valencia, and navel oranges, respectively; at that time no
      respiratory rise or ethylene production was observed. The pattern for all
      subsequent harvest revealed no postharvest rise in the respiratory rates. Lemon
      fruit, in contrast, had a continuously decreasing respiratory rate at all stages
      of ontogeny. Exposure to 20 microliters of ethylene per liter induced an increase
      in the respiratory rate of all varieties at every stage of ontogeny; this was
      true also in young oranges and grapefruit following their respiratory rise and
      decline.Evidence is presented that citrus fruits are nonclimacteric fruits.

PMID- 16657320
TI  - The growth of and organ formation from callus tissue of sorghum.

PMID- 16657321
TI  - The effects of amino acids and ammonium on the growth of plant cells in
      suspension culture.
AB  - A suspension culture of soybean (Glycine max L.) was grown on a defined medium in
      which the nitrogen sources were nitrate (25 mM) and ammonium (2 mM). The cells
      did not grow on nitrate unless the medium was supplemented with ammonium or
      glutamine. The l- and d-isomers of 12 amino acids tested singly could not replace
      ammonium. Most amino acids (4 mM) inhibited growth when the cells were cultured
      on nitrate and ammonium. Cells from five other plants (Reseda luteoli L.;
      Triticum monococcum L.; flax, Linum usitatissimum L.; horseradish, Amoracia
      lapathifolia Gilib; Haplopappus gracilis L.) grew on the defined medium with
      nitrate (25 mM) as the sole nitrogen source. Higher cell yields were obtained
      when ammonium (2 mM) or glutamine also was present. Supplementing the defined
      medium with high concentrations of ammonium (20 mM) inhibited growth of soybean,
      Haplopappus, and wheat cells. Addition of citrate (5 mM) relieved the inhibitory
      effects of ammonium in soybean and wheat cells but not in the Haplopappus cells.

PMID- 16657322
TI  - The role of phytic Acid in the wheat grain.
AB  - The concentrations of adenosine triphosphate and phytic acid in testa, embryo
      plus scutellum, aleurone, and endosperm fractions from grain of Triticum vulgare
      cv. Insignia have been determined during development under both normal conditions
      and those of water stress. Phytic acid was not detected in the endosperm. In the
      embryo plus scutellum and aleurone fractions there was a rapid build-up of phytic
      acid, but the adenosine triphosphate level did not change markedly at this time.
      These results are not consistent with physiological roles previously suggested
      for phytic acid other than the role of phytin as a phosphorus and cation store
      for the germinating seed.

PMID- 16657323
TI  - The environmental control of cold acclimation in apple.
AB  - The role of photoperiod and temperature in the cold acclimation of living
      Haralson apple (Pyrus malus L.) bark was studied in the autumn under field
      conditions in Minnesota. Whole trees, or different parts of the same tree, were
      exposed to either natural conditions, artifically lengthened days, or
      artificially warmed nights, or they were subjected to manual leaf removal. The
      results indicate that acclimation occurs in two stages which are induced by short
      days and frost (or low temperature), respectively. Leaves were stimulated by
      short days to produce translocatable substance(s) which promoted cold acclimation
      of the living bark. Leaves of plants grown under long days were the source of a
      translocatable substance(s) which inhibited acclimation. The second stage of
      hardiness, induced by frost (or low temperature), did not involve translocatable
      factors.Inductive short days could overcome the effect of high temperatures, and
      low temperatures could overcome the effect of noninductive long days in promoting
      the first stage of acclimation to -30 C. Frost was necessary for maximum
      hardiness to -55 C. Plants grown in a greenhouse, in the autumn, under long days
      and high temperatures acclimated slightly in spite of the noninductive
      conditions. Short days and frost (or low temperatures) appeared to regulate
      different and independent endogenous acclimation processes.

PMID- 16657324
TI  - An anomaly in potassium accumulation by barley roots: I. Effect of anions, sodium
      concentration, and length of absorption period.
AB  - Excised barley roots accumulated 40 to 50% more K(+) from 0.04 mm than from 0.06
      mm KCl when incubated for 24 hours in KCl solutions containing 0.2 mm CaSO(4).
      This phenomenon was not markedly influenced by the rate of absorption of the
      counteranion. The presence of Na(+) in the treatment solutions decreased total K
      accumulation but did not alter the K(+) concentration at which the accumulation
      peak occurred. Short interval studies indicated that this phenomenon is easily
      observable after 4 hours and begins to become apparent within 2 hours. In
      comparison with barley, accumulation of K(+) by excised wheat roots decreased as
      KCl concentration was increased from 0.02 to 0.06 mm; but K(+) accumulation curve
      for corn roots showed no peaks or depressions in the concentration range of 0.01
      to 0.1 mm. A normal hyperbolic curve was noted for the accumulation of Na(+) from
      0.01 to 1 mm NaCl by barley roots.

PMID- 16657325
TI  - An Anomaly in Potassium Accumulation by Barley Roots: II. Effect of Calcium
      Concentration and Rubidium-86 Labeling.
AB  - When excised barley roots were incubated in 0.01 to 0.1 mm KCl solutions
      containing 0.2 mm CaSO(4), there was a peak in the K(+) accumulation against
      concentration curve at 0.02 to 0.04 mm KCl. The peak in the K(+) accumulation
      curve was shifted to lower K(+) concentrations when Ca(2+) concentration was
      decreased and to higher K(+) concentrations when Ca(2+) concentration was
      increased. Increasing Ca(2+) concentration in the treatment solution was observed
      to be stimulatory, inhibitory, or neutral depending on the K(+)
      concentration.When (86)Rb was used as an isotopic tracer for K(+), accumulation
      of K(+) was grossly overestimated, and the apparent K(+) accumulation curve, as
      estimated with (86)Rb-labeled K(+), was hyperbolic over the concentration range
      of 0.01 to 0.1 mm. It was concluded that (86)Rb is a poor tracer for K(+) over
      the concentration range of 0.01 to 0.1 mm. Accumulation of Rb(+) in the presence
      of K(+) was accurately measured by (86)Rb.

PMID- 16657326
TI  - Stomatal Responses to Pressure Changes and Interruptions in the Water Supply of
      Detached Leaves of Zea mays L.
AB  - Stomata of Zea mays L. respond to changes in hydrostatic pressure in the water
      supply of the leaves almost instantaneously and in all leaf parts simultaneously.
      Therefore, the leaf is a hydraulic unit. The stomata are part of it and their
      aperture is controlled by the water potential in the water-conducting system.
      Stomatal aperture is not uniquely related to the relative water content of a
      leaf. The relation depends also on the humidity in the air and is different for
      the upper and the lower epidermis.

PMID- 16657327
TI  - Increase in indoleacetic Acid oxidase activity of winter wheat by cold treatment
      and gibberellic Acid.
AB  - The activity of indoleacetic acid oxidase increased 10-fold during 40 days of
      cold treatment of winter wheat seedlings. Puromycin and 6-methyl purine inhibited
      indoleacetic acid oxidase development in the cold. Addition of gibberellic acid
      stimulated indoleacetic acid oxidase development during germination at room
      temperature and during cold treatment. Amo-1618 inhibited indoleacetic acid
      oxidase development before and during cold treatment. Indoleacetic acid treatment
      increased indoleacetic acid oxidase activity during germination at room
      temperature while no significant effect on activity was observed during cold
      treatment.

PMID- 16657328
TI  - Glycolate formation in intact spinach chloroplasts.
AB  - Photosynthetic (14)CO(2) fixation and the accumulation of photosynthetic products
      and the response of each process to both 3-(3,4-dichlorophenyl)-1, 1-dimethylurea
      (DCMU) and ascorbate were investigated in the intact spinach
      chloroplast.Ascorbate increased the rate of CO(2) uptake with an increase in all
      photosynthetic products, but, proportionally, there was a much larger increase in
      glycolate formation. CO(2) fixation inhibited by DCMU was partially restored on
      addition of ascorbate. Under conditions not optimal for glycolate formation, such
      as saturating levels of CO(2) and an anaerobic atmosphere, ascorbate in the
      presence of DCMU restored the formation of all photosynthetic products excluding
      glycolate. This effect of ascorbate on glycolate synthesis in the presence of
      DCMU was diminished under conditions which favored glycolate formation.
      Externally added glycerate 3-phosphate and fructose 1,6-diphosphate depressed the
      appearance of radioactivity in glycolate.The data are interpreted to indicate
      that glycolate is produced during photosynthesis as a result of a reaction
      between a 2-carbon piece derived from a sugar phosphate and an oxidant generated
      by the photochemical act. The oxidant may be an intermediate of photosystem 2 or
      a peroxide generated by a mechanism of the Mehler type involving molecular
      oxygen.

PMID- 16657329
TI  - Carbowax 6000 compared with mannitol as a suppressant of cucumber hypocotyl
      elongation.

PMID- 16657330
TI  - Retention of calcium-45 by dogwood trees.

PMID- 16657331
TI  - Quinone Changes during Bud Opening.

PMID- 16657332
TI  - Incorporation of p in seeds at low water potentials: evaluation of
      microbiological contamination.

PMID- 16657333
TI  - Effect of Indole-3-acetic Acid on Membrane Potentials of Oat Coleoptile Cells.

PMID- 16657334
TI  - Diurnal variations in root diameter.

PMID- 16657335
TI  - Ethylene production by citrus fruit peel: stimulation by phenol derivatives.

PMID- 16657336
TI  - Interaction of kinetin and abscisic Acid in the growth of soybean callus.

PMID- 16657337
TI  - The use of dimethylsulfoxide as a solvent in the tobacco bioassay for cytokinins.

PMID- 16657338
TI  - Polar Movement of Gibberellic Acid through Young Coleus Petioles.

PMID- 16657339
TI  - Gas-Liquid Chromatographic Isolation of Cytokinins from Natural Sources: 6-(3
      Methyl-2-butenylamino) purine from Agrobacterium Tumefaciens.
AB  - Gas-liquid chromatographic retention times for 20 purines or purine nucleosides,
      14 of which are highly active cytokinins, are reported. With one exception, all
      of the naturally occurring cytokinins are separated.Ethyl acetate extraction of
      yeast transfer RNA hydrolysates and of culture filtrates of Agrobacterium
      tumefaciens gave sufficient concentration of the naturally occurring cytokinins
      for immediate gas-liquid chromatography. This procedure permitted the detection
      of 6-(3-methyl-2-butenylamino)-9-beta, d-ribofuranosylpurine in yeast transfer
      RNA extracts. An active cytokinin was isolated from A. tumefaciens culture
      filtrates and was tentatively identified as 6-(3-methyl-2-butenylamino)purine.

PMID- 16657340
TI  - Factors involved in the opening of the hypocotyl hook of cotton and beans.
AB  - Conditions influencing the opening of the bean (Phaseolus vulgaris L.) and cotton
      (Gossypium hirsutum L.) hypocotyl hook were defined. Such hooks were shown to
      undergo geotropic curvature; orientation of the hook with respect to gravity
      greatly affected the observed opening. Cotton and bean hooks behaved exactly
      opposite in regard to the presence of the cotyledons and apical bud. The cotton
      hook required the cotyledons for opening, but the corresponding tissue slowed or
      inhibited opening of the bean hook. With cotton, lower hypocotyl and root tissues
      stimulated hook opening, but with bean, the tissues below the hook section had
      little effect. Kinetin and gibberellic acid both modified hook opening in light
      and dark; the former was inhibitory and the latter was stimulatory. Indoleacetic
      acid, at concentrations above 10(-5) M, caused pronounced hook closing in red
      light but not in the dark. These effects were generally the same with both
      plants. In opening of the cotton hook, the cotyledons were not necessary as a
      light receptor tissue. None of the growth substances tested were able to
      substitute completely for the cotton cotyledon. Coumarin was a pronounced
      inhibitor of opening of the cotton hook, and this response was expressed to such
      a degree as to cause hook closure with bean tissue. Reduced oxygen levels
      inhibited hook opening in bean. Oxygen was required in processes subsequent to
      the light reaction, but not for the photochemical process.

PMID- 16657341
TI  - Involvement of ethylene in responses of etiolated bean hypocotyl hook to
      coumarin.
AB  - Coumarin, at concentrations between 1.0 and 0.1 mm, inhibited red light-induced
      opening of the etiolated bean hypocotyl hook. In addition, anthocyanin synthesis
      and geotropic bending were inhibited. Coumarin stimulated ethylene synthesis, and
      ethylene was shown to mediate the inhibitory actions of coumarin. This conclusion
      was supported by: (a) the parallel concentration dependence and time sequence of
      hook closing and ethylene synthesis, (b) the restriction of the bulk of coumarin
      induced ethylene production to the curved portion of the hook where opening is
      expressed, (c) the ability of both coumarin and ethylene to reclose partially
      opened hooks, and (d) the ability of exogenous ethylene, in the amounts produced
      by coumarintreated hooks, to duplicate the inhibitory effects of coumarin. There
      was an increasing stimulation of growth of the straight portion of the hypocotyl
      hook section as coumarin concentrations were increased from 0.1 to 1.0 mm. This
      action of coumarin was not duplicated by ethylene and occurred regardless of the
      presence or absence of added ethylene. The results of this study suggest that
      many actions of coumarin in growth systems are mediated by ethylene produced in
      response to the coumarin.

PMID- 16657342
TI  - Some effects of hydrolytic enzymes on coupled and uncoupled electron flow in
      chloroplasts.
AB  - Digestion of spinach chloroplasts with pancreatic lipase or trypsin effectively
      uncoupled electron transport. Continued digestion led to inhibition of saturated
      rates of Hill reaction activity and a decrease in quantum yield. Irradiation with
      ultraviolet light decreased the quantum yield and inhibited Hill activity, but
      did not uncouple. Ascorbate-dichlorophenol-indophenol-mediated reduction of
      nicotinamide adenine dinucleotide phosphate was not appreciably inhibited by
      treatment with either of the enzymes or by ultraviolet
      irradiation.Carbonylcyanide m-chlorophenylhydrazone became a potent inhibitor of
      electron transport after trypsin treatment of chloroplasts. It also inhibited,
      rather than uncoupled, electron transport in glutaraldehyde-fixed chloroplasts.
      No other uncouplers tested showed these effects. Glutaraldehyde fixation of
      chloroplasts also greatly reduced the inhibitory effects of lipase and trypsin
      digestion but not the inhibition by ultraviolet irradiation.The inhibitory
      effects of trypsin and pancreatic lipase, and probably ultraviolet irradiation as
      well, appear to be due to a general breakdown of the membrane structure rather
      than inactivation of specific sites in the electron transport chain.

PMID- 16657343
TI  - Immunochemical and spectroscopic evidence for protein conformational changes in
      phytochrome transformations.
AB  - Phytochrome was examined by immunochemical and spectroscopic techniques to detect
      differences between the protein moieties of red- and far red-absorbing
      phytochrome (P(r) and P(fr)). No differences in the reaction of P(r) and P(fr)
      with phytochrome antibody were discernible on Ouchterlony double diffusion
      plates. However, the microcomplement fixation assay showed a greater degree of
      antibody reaction with P(fr) than with P(r), indicating some difference in the
      surface characteristics of the two forms. Circular dichroism spectroscopy between
      300 and 200 nanometers revealed differences between P(r) and P(fr) which may
      reflect differences in the protein conformation. The circular dichroism spectrum
      of P(r) showed a negative band at 285 nanometers which was not present in the
      spectrum of P(fr), and the large negative circular dichroism band at 222
      nanometers with P(fr), associated with the alpha-helical content, was shifted 2
      nanometers to shorter wave length with P(r) although there was no change of
      magnitude of this band. The absorbancy of P(r) and P(fr) is very nearly the same
      in the 280 nanometer spectral region, but sensitive difference spectra between
      P(r) and P(fr) did reveal spectra which were similar to solvent perturbation
      spectra obtained by others with different proteins. In total, the experiments
      indicate that there are conformational differences between the protein moieties
      of P(r) and P(fr) but that these differences are rather slight from a standpoint
      of gross structure.

PMID- 16657344
TI  - Time course of exudation from excised corn root segments of different stages of
      development.
AB  - Xylem exudates were collected at hourly intervals from short segments which had
      been excised from two portions of the primary root of corn (Zea mays L.)
      seedlings and partially immersed in experimental salt solution containing (86)Rb.
      All segments showed variation in rates of output of both volume and ions for
      several hours, after which a steady state was attained which persisted for many
      hours. Apical segments produced little or no exudate for several hours and did
      not reach a steady state until 18 or more hours after excision. Basal segments
      produced exudate containing detectable quantities of isotope within an hour and
      they reached a steady state about 12 hours after excision. During their
      respective steady states, apical segments produced three times the volume per
      hour and translocated eight times as much Rb per hour as did basal segments.These
      differences in the time course of exudation and the large differences in output
      are interpreted as indicating that two independent systems of ion transport
      operate simultaneously in intact roots. If this interpretation is correct, then
      it would appear that one of these systems has a greater potential capacity for
      ion transport than the other.

PMID- 16657345
TI  - Movement of (RS)-Abscisic Acid in the Cotton Explant.
AB  - The movement of abscisic acid in the cotton explant was investigated by bioassay
      and radioisotope techniques. The rate of movement was 20 to 30 millimeters per
      hour with most of the abscisic acid moving unchanged through the explant into the
      basal agar. The rate of movement was the same through the abscission zone as
      through petiole tissue. Patterns of accumulation and metabolic products are
      discussed.

PMID- 16657346
TI  - Influence of age and illumination on distribution of several calvin cycle enzymes
      in greening barley leaves.
AB  - Activities of phosphoriboisomerase, phosphoribulokinase, and ribulose 1,5
      diphosphate carboxylase, protein content, and chlorophyll accumulation in dark
      grown barley seedlings were measured before and after illumination. Enzymatic
      activities, levels of soluble protein, and accumulation (upon illumination) of
      chlorophyll in leaves declined from tips toward the base. In response to
      increasing time of illumination, chlorophyll accumulation and activities of
      phosphoribulokinase and ribulose 1,5-diphosphate carboxylase (enzymes located in
      chloroplasts) increased most in tip portions whereas activity of
      phosphoriboisomerase and levels of soluble protein (constituents not confined to
      chloroplasts) increased similarly in all sections of the leaf. Maximum activity
      of phosphoribulokinase and maximum accumulation of chlorophyll shifted toward
      median portions of the leaf blade with increased age of seedling before
      illumination. Maximum activity of ribulose 1,5-diphosphate carboxylase and
      maximum level of soluble protein occurred in all leaf sections when the seedlings
      were 7 days of age before illumination.

PMID- 16657347
TI  - Chloroplast and cytoplasmic enzymes: three distinct isoenzymes associated with
      the reductive pentose phosphate cycle.
AB  - Three pea (Pisum sativum) leaf chloroplast enzymes-triose phosphate isomerase,
      glyceric acid 3-phosphate kinase, and fructose 1,6-diphosphate aldolase-have been
      separated from the corresponding cytoplasmic enzymes by isoelectric focusing.
      These three enzymes of the reductive pentose phosphate cycle are therefore
      distinct proteins, not identical with the analogous enzymes of the Embden
      Meyerhof-Parnas pathway.

PMID- 16657348
TI  - Effects of Helminthosporium victoriae Toxin on Germination and Aleurone Secretion
      by Resistant and Susceptible Seeds.
AB  - Oat seeds of cultivars susceptible and resistant to Helminthosporium victoriae
      were held for various times in pathogen-produced, host-specific toxin solutions;
      control seeds were in water. Seeds were then washed thoroughly and incubated on
      moist paper, or dried and stored for 2-3 weeks before germination was attempted.
      In both cases, germination of susceptible seeds was prevented by previous
      exposure to toxin for 1 hour or more. Control seeds and treated resistant seeds
      grew normally. Toxin did not affect O(2) uptake or loss of carbohydrates from
      seeds for the first 12 hours of imbibition. After 12 hours, toxin-treated
      susceptible seeds had higher respiration and lost more carbohydrates than did
      control seeds. Experiments with embryoless seeds showed that toxin blocked
      synthesis and secretion of alpha-amylase by susceptible but not by resistant
      aleurone cells. Resting aleurone cells were exposed briefly to toxin, then dried
      and stored until all toxin was gone. Susceptible aleurone cells treated in this
      way failed to produce alpha-amylase following exposure to gibberellic acid, while
      controls and resistant treated aleurone tissues produced amylase. Susceptibility
      or resistance to toxin appears to be expressed in resting and metabolically
      active tissues.

PMID- 16657349
TI  - Influence of nickel on the detection of nitrate reductase activity in sorghum
      extracts.
AB  - The addition of nickel (4 x 10(-3)m) to the extracting buffer enhances the
      nitrate reductase activity in preparations of young grain sorghum (Sorghum
      bicolor L. [Moench] leaf tissue by as much as 6-fold. Activities comparable to
      other plant species are obtained over an extraction pH range of 7 to 8 with tris
      buffer and reduced nicotinamide adenine dinucleotide as a cofactor for the
      reaction when the ratio of plant material to extraction medium is 1:20. The
      method also enhances nitrate reductase activity in sudangrass (Sorghum sudanense
      P. [Stapf]).

PMID- 16657350
TI  - The culture of plant cells with ammonium salts as the sole nitrogen source.
AB  - Soybean cell suspension cultures grew on defined media with ammonium as the sole
      nitrogen source if Krebs cycle acids were added. Satisfactory growth was obtained
      with ammonium salts of citrate, malate, fumarate, or succinate, when compared
      with the regular medium containing nitrate and ammonium. Little or no growth
      occurred when ammonium salts of shikimate, tartrate, acetate, carbonate, or
      sulfate were used. The cells also grew well with l-glutamine as nitrogen source.
      The specific activities of glutamine synthetase and isocitrate dehydrogenase
      (nicotinamide adenine dinucleotide phosphate) were lower than in cells grown on a
      nitrate medium, but ammonium enhanced the activity of glutamate dehydrogenase.
      Cells of soybean, wheat, and flax have been cultured for an extended period on
      the ammonium citrate medium.

PMID- 16657351
TI  - Potassium Fluxes during Potassium Absorption by Intact Barley Plants of
      Increasing Potassium Content.
AB  - The presence of previously absorbed K in plants caused a marked reduction in the
      short term influx of (86)Rb-labeled K into roots of barley seedlings. The influx
      values agreed with net K absorption rates into intact plants, thus suggesting
      that K efflux was negligible in comparison with influx.Earlier interpretations of
      a large K efflux component from excised roots approaching equilibrium K
      concentrations are considered to be due to an underestimation of net K absorption
      rates resulting from xylem exudation as the K status of the roots increased.

PMID- 16657352
TI  - Effects of iron and copper ions in promotion of selective abscission and ethylene
      production by citrus fruit and the inactivation of indoleacetic Acid.
AB  - Application of Cu(2+) (<10(-2) M) and Fe(3+) ions as aqueous solutions of
      chloride salts promoted fruit abscission, erratic rind damage, and ethylene
      production of various citrus species with little to no defoliation. Mixing of 10(
      5) M Cu(2+) or Fe(3+) ions with equimolar indole-3-acetic acid resulted in a
      reduction of the ultraviolet absorption at 220 nanometers, and an increase at 245
      nanometers. Ultraviolet irradiation accelerated the change by Fe(3+) and Cu(2+)
      ions in the absorption of indole-3-acetic acid. Pretreatment of indole-3-acetic
      acid with Fe(3+) and Cu(2+) ions for 6 hours resulted in more than 90% reduction
      in its growth-promoting activity in the Avena bioassay, even when cations were
      removed by chromatography. Acceleration of abscission by Fe(3+) and Cu(2+) ions
      could be related to both promotion of ethylene production and direct inactivation
      of auxin.

PMID- 16657353
TI  - Deoxyribonucleic Acid-dependent Ribonucleic Acid Polymerase Activity of Nuclei
      and Plastids from Etiolated Peas and their Response to Red and Far Red Light in
      Vivo.
AB  - DNA-dependent RNA polymerase activity has been found in both the nuclei and
      etioplasts of dark-grown pea seedlings (Pisum sativum). Although these enzymes
      had similar over-all characteristics with respect to substrate, pH, and inhibitor
      responses, they could be distinguished by their different sensitivities to
      sonication.Brief irradiation of the seedlings with red light resulted in an
      increase in the activity of both the nuclear and plastid enzymes, but the time
      course of this response showed it to be too slow to be considered an early result
      of phytochrome control of metabolism. Far red light following red treatment
      largely prevented the increase in the activity of the nuclear enzyme. The plastid
      enzyme responded to far red light in a manner similar to its response to red
      light so that no reversal was observed when far red treatment followed red.

PMID- 16657354
TI  - Inhibition of oxygen evolution in chloroplasts isolated from leaves with low
      water potentials.
AB  - Chloroplasts were isolated from pea and sunflower leaves having various water
      potentials. Oxygen evolution by the chloroplasts was measured under identical
      conditions for all treatments with saturating light and with dichloroindophenol
      as oxidant. Evolution was inhibited when leaf water potentials were below -12
      bars in pea and -8 bars in sunflower and the inhibition was proportional to leaf
      water potential below these limits. Inhibition was more severe in sunflower than
      in pea chloroplasts. In sunflower, it could be detected after 5 minutes of leaf
      desiccation, and, up to 1 hour, the effect was independent of the duration of low
      leaf water potential.In high light, the reduction in activity of sunflower
      chloroplasts paralleled the reduction in CO(2) fixation by intact sunflower
      plants having low leaf water potentials. Stomatal apertures and transpiration
      rates were also reduced under these conditions and were probably limiting. In low
      light, intact sunflowers required more light per unit of CO(2) fixed when leaf
      water potentials were low than when they were high. This increased light
      requirement in the intact system was of a magnitude which could be predicted from
      the reduced oxygen evolution by the isolated chloroplasts. It was concluded that
      moderately low leaf water potential affects photosynthesis in at least two ways:
      first, through an inhibition of oxygen evolution by chloroplasts and, second, by
      closure of stomata in intact leaves.

PMID- 16657355
TI  - Physicochemical studies on the proteins of the peanut cotyledon and embryonic
      axis.
AB  - Subcellular fractions from the cotyledon obtained by differential and density
      gradient centrifugation, and extracts of total proteins from both cotyledon and
      axial tissues were analyzed by diethylaminoethyl cellulose chromatography, zone
      electrophoresis, ultracentrifugation, immunodiffusion, and immunoelectrophoresis.
      Fractionation and characterization of proteins in subcellular organelles of the
      peanut reaffirm that alpha-arachin is located in the protein bodies of the cells.
      Results obtained by diethylaminoethyl cellulose chromatography of subcellular
      fractions suggest that some of the conarachin proteins are cytoplasmic. alpha(1)
      Conarachin is cytoplasmic, and alpha(2)-conarachin is particle-bound. alpha
      Arachin and alpha(2)-conarachin predominate in the cotyledon. Quantitative
      differences for other proteins were also observed. Although qualitative
      similarities are apparent by immunoelectrophoresis, major differences were
      observed in the sedimentation patterns, zone electrophoreograms, and in the
      diethylaminoethyl cellulose chromatograms of total protein extracts from the
      cotyledon and the axis.

PMID- 16657356
TI  - Effects of ethylene and 2-chloroethylphosphonic Acid on the ripening of grapes.
AB  - The effects of ethylene gas, 2-chloroethylphosphonic acid, and the auxin,
      benzothiazole-2-oxyacetic acid, on the ripening of grapes (Vitis vinifera L.) was
      investigated. Ethylene hastened the start of ripening of Doradillo grapes when it
      was aplied for 10 days starting midway through the slow growth phase. 2
      Chloroethylphosphonic acid applied to Shiraz grapes showed the same effect, but
      when it was applied earlier, during the second half of the first rapid growth
      phase or at the start of the slow growth phase of berry development, it delayed
      ripening. 2-Chloroethylphosphonic acid and benzothiazole-2-oxyacetic acid delayed
      the ripening of Doradillo grapes, and ethylene partially reversed the effect of
      benzothiazole-2-oxyacetic acid. The results demonstrate the importance of the
      slow growth stage in grape berry development and suggest that an auxin-ethylene
      relationship may be involved in the regulation of grape ripening.

PMID- 16657357
TI  - Photoreduction of alpha-Ketoglutarate to Glutamate by Vicia faba Chloroplasts.
AB  - Intact chloroplasts isolated from leaves of Vicia faba L. var. the Sutton show a
      decline in the endogenous level of alpha-ketoglutarate upon illumination. alpha
      Ketoglutarate supplied to the chloroplasts is similarly utilized in this light
      dependent reaction, and its consumption is paralleled by a concomitant increase
      in the level of glutamate. There is no photostimulation of glutamate synthesis in
      chloroplasts broken by osmotic shock, but it can be somewhat restored by addition
      of ferredoxin and NADP. These results suggest that in the isolated chloroplast
      the synthesis of glutamate from alpha-ketoglutarate is regulated by the
      availability of reduced pyridine nucleotide generated by photosynthetic electron
      transport. This conclusion is supported by the finding of an apparent competition
      between the photoreduction of phosphoglycerate to triose phosphate and the
      photoutilization of alpha-ketoglutarate.

PMID- 16657358
TI  - Ethylene production by autoclaved rubber injection caps used in biological
      systems.

PMID- 16657359
TI  - Effect of chloramphenicol on amino Acid incorporation by chloroplasts and
      comparison with the effect of chloramphenicol on chloroplast development in vivo.

PMID- 16657360
TI  - Sterol Changes in Maize Leaves Infected with Helminthosporium carbonum.

PMID- 16657361
TI  - Effect of ethionine on invertase development and methylation of ribonucleic Acid.

PMID- 16657362
TI  - Transport of potassium and rubidium in plant roots: the significance of calcium.

PMID- 16657363
TI  - Turnover in the transportable pool of auxin.

PMID- 16657364
TI  - Ethylene inhibition of auxin transport by gravity in leaves.

PMID- 16657365
TI  - Circadian leaf movements in biloxi soybeans.

PMID- 16657366
TI  - Divalent cation stimulation of substrate oxidation by corn mitochondria.
AB  - The oxidation of reduced nicotinamide adenine dinucleotide, malate-pyruvate, and
      succinate by corn mitochondria in buffered 0.2 m KCl was determined as a function
      of divalent cations. Ni(2+), Mg(2+), Co(2+), Ca(2+), Mn(2+), Sr(2+), and Ba(2+)
      stimulated reduced nicotinamide adenine dinucleotide oxidation in the absence of
      inorganic phosphate, with Ca(2+) and Sr(2+) having the greatest effect. Malate
      pyruvate and succinate oxidation was stimulated by Ca(2+), Ba(2+), and Sr(2+),
      but only in the presence of inorganic phosphate. Ca(2+), Sr(2+), and Ba(2+)
      produced a simulated state 4 to state 3 transition with all three substrates, but
      only with malate-pyruvate and succinate was there a return to state 4. The order
      of divalent cation effectiveness suggests that the rate of water substitution
      from the cation inner coordination hydration sphere may be a rate-limiting step
      in certain mitochondrial reactions involving electron transport and
      phosphorylation.

PMID- 16657367
TI  - Applied auxin gradients and abscission in explants.
AB  - The influence of applied auxin on abscission in explants (excised cotyledonary
      nodes) of cotton was investigated.Proximal applications to the stem stump
      accelerated abscission with all concentrations applied. Distal applications to
      the petiole stumps retarded abscission with all concentrations
      applied.Simultaneous applications to petiole and stem stumps accelerated,
      retarded, or were without effect on abscission depending on the relative amounts
      applied. Relatively high concentrations proximal on stem stumps accelerated
      abscission whereas relatively high concentrations distal on petiole stumps
      retarded abscission. The abscission rates from various combinations resulted in a
      multiphasic abscission response curve as the amounts applied were
      increased.Consideration of these and related data in the literature indicates
      that many factors can have profound effects on the nature of abscission responses
      to auxin.

PMID- 16657368
TI  - Metabolically active glucosides in oleaceae seeds: I. The effects of germination,
      growth, and hormone treatments.
AB  - The seeds of six woody species of Oleaceae representing three genera, contain
      high concentrations of water-soluble glucosides, with major absorption maxima
      below 240 nanometers. In Fraxinus americana seeds three of these compounds,
      designated GL-3, GL-5, and GL-6, account for almost 10% of the dry weight. They
      are found in the endosperm and embryo but not in the pericarp. While the level of
      GL-5 is not particularly influenced by the physiological state of the embryo,
      that of GL-3 and GL-6 decreases as a result of germination and growth during a 10
      day period. As the concentrations of GL-3 and GL-6 decrease, new ultraviolet
      absorbing compounds are formed. The changes in the concentration of the
      ultraviolet-absorbing glucosides during cold temperature after-ripening, prior to
      germination, are small. When germination of dormant embryos is induced with
      gibberellic acid, the concentrations of GL-3 and GL-6 decrease in a manner
      similar to that observed with nondormant embryos. In the presence of abscisic
      acid no losses of GL-3 and GL-6 were observed. It is suggested that GL-3 and GL-6
      fulfill some definite functions in the germination and growth of F. americana
      embryos, and that gibberellic acid and abscisic acid can exert a regulatory
      effect on the metabolism of these glucosides.

PMID- 16657369
TI  - Sterol distribution in intracellular organelles isolated from tobacco leaves.
AB  - All membrane-containing fractions isolated from tobacco leaves contained free
      sterols, sterol glycosides, and sterol esters. The three sterol forms increased,
      on a dry weight basis, with a decrease in particle size. The supernatant fraction
      contained only trace amounts of sterol. The major sterols in all cellular
      fractions, in the order of decreasing amounts, were: stigmasterol, beta
      sitosterol, campesterol, and cholesterol. The 500g pellet contained the largest
      percentage of free sterol, while the 46,000g pellet contained the largest
      percentage of esterified sterol. The individual sterol composition of the free
      sterol and sterol glycoside fraction was very similar; however, the composition
      of the sterol ester fraction varied widely among intracellular fraction. The
      intracellular distribution pattern of cholesterol-(14)C added to the isolation
      medium provided evidence that the intracellular sterol distribution pattern is
      not an artifact. These results support the suggestion that sterols in plant cells
      may have a physiological function associated with membranes.

PMID- 16657370
TI  - Radial movement of oxygen in plant roots.
AB  - The radial movement of oxygen in excised corn and jack bean roots was measured
      with a platinum wire electrode embedded in the root tissue. Measurements were
      made with the roots exposed to air and with the roots immersed in nutrient
      solution in the presence and absence of millimolar sodium azide. Effective rates
      of oxygen diffusion in the root tissue were also measured from 5 to 30 C and
      compared to the respiration rates of similar root segments over the same
      temperature range. Under conditions which allow the roots to exude freely, the
      interior of the root operates under an oxygen deficit. Inhibition of respiratory
      oxygen uptake by low temperature or azide treatment increased the flux of oxygen
      to the root interior.

PMID- 16657371
TI  - Calcium transport in apple trees.
AB  - (45)Ca, applied to roots of apple seedlings, moved readily to the developing
      leaves. Kinetin, benzyladenine, and B sprays increased movement. NO(3) (-) as the
      source of N increased movement and accumulation of Ca into mature leaves; NH(4)
      (+) increased movement into new leaves. Translocation in the stem is effected by
      a nonspecific ion exchange. Any divalent cation can free Ca for ascent. The
      exchange may be a property of lignin. Genetic differences in the uptake and
      translocation of Ca exist among apple seedlings. Those which show juvenile leaf
      characteristics translocate Ca into mature leaves more readily. Translocation of
      Ca in woody species appears to be similar to that reported for herbaceous plants.

PMID- 16657372
TI  - The Involvement of Glycosidases in the Cell Wall Metabolism of Suspension
      cultured Acer pseudoplatanus Cells.
AB  - Several glycosidases have been isolated from suspensioncultured sycamore (Acer
      pseudoplatanus) cells. These include an alpha-galactosidase, an alpha
      mannosidase, a beta-N-acetyl-glucosaminidase, a beta-glucosidase, and two beta
      galactosidases. The pH optimum of each of these enzymes was determined. The pH
      optima, together with inhibition studies, suggest that each observed glycosidase
      activity represents a separate enzyme. Three of these enzymes, beta-glucosidase,
      alpha-galactosidase, and one of the beta-galactosidases, have been shown to be
      associated with the cell surface. The enzyme activities associated with the cell
      surface were shown to possess the ability to degrade to a limited extent isolated
      sycamore cell walls. It was found that the activities of beta-glucosidase and of
      one of the beta-galactosidases increase as the cells go through a period of
      growth and decrease as cell growth ceases.

PMID- 16657373
TI  - Some spectral properties of pea phytochrome in vivo and in vitro.
AB  - The transformation difference spectrum for phytochrome (Pr spectrum minus Pfr
      spectrum) in pea tissue is determined below 560 nanometers and compared with
      similar data on phytochrome in vitro The difference spectrum in vivo between
      phytochrome intermediates and Pfr is also shown for comparison with the data on
      phytochrome solutions. These comparisons show that the peaks in the spectra
      occurring in the blue wave lengths are shifted to shorter wave lengths and are
      much enhanced when phytochrome is extracted from the cell and placed in solution.
      The results indicate that the physicochemical state of phytochrome in the cell
      may be different from that of the extracted pigment.

PMID- 16657374
TI  - Lipids in alfalfa leaves in relation to cold hardiness.
AB  - The lipid composition of the leaves of hardy Vernal and cold-sensitive Caliverde
      alfalfa plants, grown at different temperatures, was determined. Phosphatidyl
      glycerol, phosphatidyl inositol, and the sulfolipid content were directly related
      to growth temperature. Mono- and digalactose diglyceride and phosphatidyl choline
      and ethanolamine were inversely related to temperature. At corresponding growth
      temperatures Vernal plants showed higher percentages of mono- and digalactose
      diglyceride and phosphatidyl choline and ethanolamine than Caliverde plants,
      while the opposite was true for phosphatidyl glycerol and inositol and
      sulfolipid. Differences in fatty acid composition of corresponding leaf lipid
      fractions of plants grown at different temperatures or differences in fatty acid
      composition between lipid fractions of plants of different varieties in general
      were negligible.

PMID- 16657375
TI  - Inhibitory Effect of Carbohydrate on Flowering in Lemna perpusilla: II. Reversal
      by Glycine and l-Aspartate. Correlation with Reduced Levels of beta-Carotene and
      Chlorophyll.
AB  - Flowering of Lemna perpusilla strain 6746 grown on 0.1 strength Hutner's medium
      in short days was inhibited by sucrose, glucose, fructose, and mannose, but not
      by various other sugars or metabolic intermediates. Only those sugars that
      inhibited flowering supported heterotrophic growth. Experiments with a single
      inductive long night indicated that an early stage in flowering was the sugar
      sensitive process. Inhibition of flowering by carbohydrates was accompanied by
      reduced levels of chlorophyll and beta-carotene. The inhibitory effects of
      carbohydrates on flowering were partially reversed by iminodiacetate, glycine,
      and l-aspartate but not by d-aspartate, ethylenediaminetetraacetate, acetate,
      delta-aminolevulinic acid, or mevalonic acid. The possibility is discussed that
      carbohydrate repression of flowering and of chloroplast pigments resulted from
      inadequate levels of amino acids.

PMID- 16657376
TI  - Abscisic Acid in tobacco plants: tentative identification and its relation to
      stunting induced by pseudomonas solanaccarum.
AB  - In tobacco plants inoculated with the wilt-inducing bacterium, Pseudomonas
      solanacearum, there was a correlation between decreased internode elongation,
      maximum multiplication of the bacterium, and an increase in the growth inhibitor
      content of stems 4 to 12 days after inoculation, as determined by a wheat
      coleoptile assay. Initial wilting of the upper leaves was also correlated with an
      increase in inhibitor content of these tissues.Application of either the
      partially purified inhibitor from tobacco or pure (+)-abscisic acid to roots,
      terminal buds, or petioles of tobacco plants caused a reduction of internode
      length which lasted from 8 to 10 days following a single treatment. Repeated
      treatment was necessary to obtain growth retardation over a longer period of
      time.The tobacco inhibitor was tentatively identified as abscisic acid, based on
      a comparison with authentic abscisic acid on paper, thin layer, column, and gas
      liquid chromatography. On the basis of optical rotatory dispersion, circular
      dichroism, and ultraviolet spectra, the tobacco inhibitor was indistinguishable
      from abscisic acid. Increases in the inhibitor content of infected tissues are
      attributed primarily to abscisic acid although other substances, not separable
      from abscisic acid by the procedures used, could also play a role. The inhibitor
      was not found in P. solanacearum culture medium.

PMID- 16657377
TI  - Changes in Respiration and Cyanide Sensitivity of the Barley Floret during
      Development and Maturation.
AB  - The 6-week period of development and maturation of the barley (Hordeum vulgare
      L.) floret from anthesis to harvest is characterized by two phases: an early
      phase of rapid increase in respiration rate and dry weight, and a late phase
      during which respiration decreased rapidly whereas dry weight remained unchanged.
      Consumption of O(2) by the embryo changed little during the entire developmental
      period, whereas O(2) uptake by the endosperm and the lemma and palea decreased
      significantly during the late phase.Maximal inhibition of O(2) uptake by cyanide
      in whole florets and floret parts coincided with maximal respiration and growth
      rates. Differences in sensitivity of embryo and endosperm to cyanide, as the
      floret matured, appeared to be related to developmental differences between these
      two tissues. Electron micrographs of embryo and endosperm cells are presented to
      illustrate some of their ultrastructural features, both at early and late stages
      of development. Increases in O(2) uptake and cyanide sensitivity of the caryopsis
      after the lemma and palea were removed suggested that the lemma, palea, and
      pericarp contributed partly to the increased resistance of the mature floret to
      cyanide by acting as barriers to gas exchange, thus restricting the movement of
      both cyanide and oxygen into the caryopsis.

PMID- 16657378
TI  - Photosynthesis and Photorespiration in Typha latifolia.
AB  - Photosynthetic rates of Typha latifolia, the broad-leaved cattail, are the
      equivalent of rates reported in tropical grasses and other plants which
      assimilate carbon by the phosphopyruvate carboxylase reaction, but photosynthesis
      in T. latifolia proceeds by a typical Calvin cycle. Glycolate oxidase, the
      photorespiratory enzyme, is present in high concentration in this species, but
      only minor quantities of the assimilated carbon pass through the photorespiratory
      pathway. However, continued operation of the pathway is apparently essential in
      the maintenance of assimilatory capacity. Glycolate oxidase function is not
      closely coupled to stomatal operation in T. latifolia.

PMID- 16657379
TI  - The structure and biosynthesis of phosphatidyl inositol in cauliflower
      inflorescence.
AB  - Phosphatidyl inositol has been isolated from cauliflower inflorescence and
      soybean. Analysis of the fatty acid distribution showed that unsaturated fatty
      acids were preferred at position 2, and that saturated fatty acids were preferred
      at position 1.Mitochondrial preparations from cauliflower inflorescence were
      capable of synthesizing phosphatidyl inositol from myo-inositol and cytidine
      diphosphate diglyceride. The optimal pH for the reaction was 9.0. Metal ions were
      required for the reaction: Mn(2+) ions were optimally effective at 1.5 mm, and
      Mg(2+) ions were maximally effective at 30 mm. The maximal rate in the presence
      of Mn(2+) was 9 times as great as that in the presence of Mg(2+). Phosphatidyl
      inositol could also be synthesized when cytidine diphosphate diglyceride was
      replaced by cytidine triphosphate, but the pH optimum then shifted to 8.1.

PMID- 16657380
TI  - Biosynthesis of cytidine diphosphate diglyceride by enzyme preparations from
      cauliflower.
AB  - The activity of the enzyme responsible for the synthesis of cytidine diphosphate
      diglyceride has been found in the 20,000g pellet of a cauliflower (Brassica
      oleracea) inflorescence homogenate. Greater enzyme activity was found in the
      pellet after treatment with 0.02% Triton X-100, or after freezing and thawing.
      Activity was greater when fluoride was included in the reaction mixture. The
      enzyme has a pH optimum of 5.6, an optimal Mn(2+) concentration of 1mm and an
      optimal Mg(2+) concentration of 30 mm. At the optimal concentration, Mn(2+) was 4
      times better than Mg(2+). The utilization of biosynthesized cytidine diphosphate
      diglyceride can be enhanced by addition of inositol, thereby causing the
      formation of phosphatidyl inositol.

PMID- 16657381
TI  - The Cytochromes of Prototheca zopfii.
AB  - The respiratory pigments of Prototheca zopfii include seven cytochromes: two c
      type cytochromes, a soluble c(549) and a membrane bound c(551); three b-type
      cytochromes, b(555), b(559) and b(564); and cytochromes a and a(3). Cytochromes a
      and a(3) could be resolved spectrally in the alpha-band region by reducing the
      cells in the presence of methanol and cyanide. Methanol shifted the absorption
      maximum of cytochrome a from 598 to 603 nanometers and permitted dithionite (or
      substrate) to reduce the cyanide-cytochrome a(3) complex to give a well defined
      595-nanometer absorption band. Methanol did not interfere with CO binding by
      cytochrome a(3), and CO did not alter the methanol effect on cytochrome a. Azide
      and cyanide, which partially inhibited exogenous respiration, stimulated
      endogenous respiration. Frozen steady states of the electron transport chain in
      the presence of cyanide and azide indicated that the stimulation by these
      inhibitors was due to an increased autooxidation of one of the b-type
      cytochromes, possibly b(564).

PMID- 16657382
TI  - Inhibition of Respiration in Prototheca zopfii by Light.
AB  - Irradiation of cells of Prototheca zopfii with blue light inhibited the
      respiratory capacity of the cells. The inhibition of respiration was correlated
      with a photodestruction of cytochrome c(551), cytochrome b(559), and cytochrome
      a(3). Cytochrome c(549), cytochrome b(555), and cytochrome b(564) were unaffected
      by the irradiation treatment. The alpha-band of reduced cytochrome a was shifted
      from 599 to 603 nm by irradiation, an effect similar to that observed when
      methanol was added to nonirradiated cells. The presence of oxygen was required
      during irradiation for both photoinhibition of respiration and photodestruction
      of the cytochromes. Cytochrome a(3) was protected against photodestruction by
      cyanide. Photodestruction of these same cytochromes also occurred when washed
      mitochondria of P. zopfii were irradiated.

PMID- 16657383
TI  - Glycolic Acid Oxidase Activity in Cell-free Preparations of Blue-Green Algae.
AB  - Glycolic acid oxidase activity was detected in cell-free preparations of Anabaena
      flos-aquae and Oscillatoria sp. by the reduction of 2,6-dichlorophenolindophenol
      and by the formation of glyoxylate. Enzyme activity was localized in the 20,000
      times gravity supernatant fraction, and optimal activity was obtained at pH 8.0.
      Activity was lost on storing the preparation at 4 C and could not be restored by
      addition of flavin mononucleotide.Oxidase activity of the supernatant fraction of
      Oscillatoria sp. was slightly stimulated by addition of flavin mononucleotide,
      but that of A. flos-aquae was unaffected by addition of this cofactor. The
      formation of glyoxylate by supernatant fractions of either alga was markedly
      inhibited by the addition of alpha-hydroxysulfonates.

PMID- 16657384
TI  - P(700) activity and chlorophyll content of plants with different photosynthetic
      carbon dioxide fixation cycles.
AB  - Representative plants containing either the reductive pentose phosphate cycle or
      the C(4) dicarboxylic acid cycle of photosynthetic carbon dioxide fixation have
      distinctly different contents of P(700) and chlorophylls a and b. With leaf
      extracts and isolated chloroplasts from C(4) cycle plants, the mean value of the
      relative ratio of P(700) to total chlorophyll was 1.83 and the mean value of the
      ratio of chlorophyll a to b was 3.89. The respective values in similar extracts
      and chloroplasts from pentose cycle plants are 1.2 and 2.78.It seems likely that
      these results are indicative of a more active Photosystem I or a different size
      photosynthetic unit in C(4) cycle plants than in the reductve pentose phosphate
      cycle plants.

PMID- 16657385
TI  - The Turnover of Nucleic Acids in Lemna minor.
AB  - A method is described for measuring the rate constants of both synthesis and
      degradation of nucleic acids in sterile growing cultures of Lemna minor which
      avoids the difficulties of environmental changes in isotope uptake and precursor
      pool size. In fast growing cultures the half-life of ribosomal RNA has been
      estimated to be between 5 and 8 days.This half-life has been shown to consist of
      two components, cytoplasmic ribosomal RNA with a half-life of about 4 days and
      chloroplast ribosomal RNA with a half-life of about 15 days. The possible
      interference of recycling has been checked, and the evidence indicates its likely
      insignificance. "Heavy" labeling of Lemna with D(2)O and (15)NO(-) (3) has
      provided evidence for the conservation of ribosomal RNA in fast growing cultures
      and has also provided an alternative assessment of recycling. When Lemna is
      placed on water, the rate of degradation of ribosomal RNA is increased and that
      of synthesis is decreased. Under partial "step down" conditions it has been found
      that omission of either nitrate or phosphate, or calcium or magnesium leads to an
      increase in the rate of degradation of ribosomal RNA. In Lemna grown on water,
      benzyladenine increases both the synthetic and degradative rates of nucleic acid
      metabolism. Abscisic acid, on the other hand, markedly reduces the rate of
      synthesis of ribosomal RNA but leaves the degradative rate unaltered.

PMID- 16657386
TI  - Freezing injury and resistance in spinach chloroplast grana.
AB  - Spinach grana appear to be injured by the same mechanism and by the same degree
      of dehydration and volume reduction that injures animal cells. Winter-hardened or
      artificially protected grana avoid injury by permitting a reversible influx of
      solute which forestalls excessive dehydration and shrinkage.

PMID- 16657387
TI  - Physiological Studies on Pea Tendrils: VI. The Characteristics of Sensory
      Perception and Transduction.
AB  - Tendrils may be said to possess a sense of touch, and the direction and amplitude
      of the coiling response can be used to define the characteristics of this sense.
      These characteristics are, first, that the tendril will coil only in response to
      ventral mechanical stimulation, that this coiling can be inhibited by subsequent
      dorsally presented stimulation, and that dorsal stimulation alone causes no
      coiling. This phenomenon seems to be due to some asymmetry in the response
      system. Second, the nature of the response is always determined by the location
      (i.e., dorsal or ventral) of the last stimulation the tendril experienced. Third,
      the ability of dorsally presented stimulation to reverse ventrally stimulated
      coiling is gradually lost. Complete escape from reversibility is attained if the
      interval between ventral and dorsal stimulation reaches 9 minutes. Fourth, the
      magnitude of response is determined by both the number and the frequency of the
      stimuli. Both ventrally stimulated coiling and dorsally stimulated inhibition of
      coiling can be temporarily stopped by a 9-minute cold break at 10 C, given
      immediately after stimulation. As soon as the tendrils are restored to room
      temperature, they proceed to respond to the stimulus.The pulling ability of the
      tendrils generated by contact coiling, as measured by an electronic monitoring
      system, is of the order of 6 milligrams per minute. Whenever these two factors
      have been compared, pulling weight parallels contact coiling, regardless of
      treatment.The relationship between the stimulus and the response appears to
      follow rules very similar to those followed by various sensory response systems
      in animals. It is therefore proposed that many of these systems may have
      functional characteristics in common.

PMID- 16657388
TI  - The Active Site on the Phytotoxin of Corynebacterium sepedonicum.
AB  - Corynebacterium sepedonicum produces an extracellular phytotoxic glycopeptide
      that possesses a capacity to wilt plant cuttings. It has been previously
      demonstrated that the integrity of some of the membranes of the host cells is
      destroyed, suggesting the possibility that a biologically active site is present
      on the toxin molecule. The toxin was chemically altered in the following ways and
      then tested for biological activity: (a) the NH(2)-terminal group on the peptide
      portion of the toxin was blocked by the dansylation technique; (b) the OH groups
      on the sugar and amino acid residues as well as the NH groups on the amino acid
      residues were blocked by exhaustive methylation; (c) the COO(-) groups were
      converted to their respective methyl esters; (d) the peptide moiety was removed
      by pronase digestion. Experimental results indicate that the carboxyl groups of
      the nonpeptide portion of the molecule are responsible for the biological
      activity of the toxin. Other experiments showed that the toxin does not affect
      the membranes of animal cells.The biological activity of the glycopeptide, as
      well as its chemically altered derivatives, was determined by an instrument
      designated as a wilt-o-meter that quantitatively measures the strength of plant
      cuttings. A description of this instrument, how it is used, and how it can be
      manufactured is also included in this report.

PMID- 16657389
TI  - Acetate metabolism in cell suspension cultures.
AB  - Cell suspension cultures of Paul's Scarlet rose were grown over a 14-day period,
      during which a 50-fold increase in fresh weight occurred. Three phases could be
      recognized from weight, DNA determinations, and microscopic examination. From
      days 0 to 7, cell division was accompanied by cell expansion; from days 7 to 10,
      only cell expansion occurred; and from days 10 to 14, there was no further
      growth.When acetate-1-(14)C was supplied continuously to 4-day and 12-day cells,
      (14)C was readily incorporated into lipid, CO(2), organic acids, amino acids, and
      protein. In the older cells, relatively greater amounts of (14)C were recovered
      in organic and amino acids, and accumulation of (14)C in these components
      continued after a steady rate of incorporation of (14)C into protein and
      (14)CO(2) had been established.Glutamate-(14)C was the most heavily labeled
      compound recovered after a pulse of acetate-1-(14)C in both cell types and was
      depleted when acetate-1-(14)C was removed, particularly rapidly in 4-day cells.
      (14)C was rapidly lost from the malate-(14)C labeled during the pulse of acetate
      1-(14)C in 4-day cells, whereas malate-(14)C continued to increase in 12-day
      cells after the pulse. Glutamate-(14)C was shown to be the source of the (14)C
      accumulating in malate in 12-day cells.Several other soluble amino acids were
      labeled during a pulse of acetate-(14)C in both cell types. After the pulse most
      of the (14)C lost from these was recovered in the corresponding amino acid in
      protein, showing that only protein precursor pools had been labeled. The behavior
      of asparagine was exceptional since its (14)C content increased after the pulse
      and no turnover was apparent. The kinetics of labeling of aspartate, malate, and
      CO(2) showed that oxaloacetate generated in the tricarboxylic acid cycle
      following the pulse was not in equilibrium with aspartate.

PMID- 16657390
TI  - Necessary conditions for isolation of tightly coupled higher plant mitochondria.
AB  - A number of parameters associated with the isolation of plant mitochondria were
      carefully examined in the hope of optimizing the isolation technique. Dark-grown
      mung bean (Phaseolus aureus var. Jumbo) hypocotyls were used as the source of
      mitochondria. Necessary conditions for the isolation of tightly coupled plant
      mitochondria include: (a) gentle tissue disruption; (b) rigorous exclusion of
      contaminating particles from the mitochondrial fraction; (c) the use of an
      optimal grinding medium containing a high concentration of mannitol, 10 mm
      phosphate or triethanolamine buffer to maintain the pH above 7.2,
      ethylenediaminetetraacetic acid at 1 mm level, cysteine at a low concentration (0
      5 mm), and a high concentration of bovine serum albumin (0.1-1.0%); and (d) the
      use of the proper wash and suspending medium consisting of mannitol, buffer, and
      bovine serum albumin at the same concentration as in the grinding medium.

PMID- 16657391
TI  - The Biosynthesis of Sucrose and Nucleoside Diphosphate Glucoses in Phaseolus
      aureus.
AB  - Sucrose-phosphate synthetase is detectable only in intact chloroplast
      preparations of Phaseolus aureus. In contrast, sucrose synthetase and uridine
      diphosphate glucose (UDP-glucose) pyrophosphorylase activities are low in
      extracts of photosynthetic tissues of P. aureus but are high in extracts of
      nonphotosynthetic tissues. Activities for ADP-, dTDP-, CDP-, and GDP-glucose
      pyrophosphorylases are generally higher in extracts of photosynthetic tissues of
      P. aureus than in extracts of nonphotosynthetic tissues. The high levels of
      sucrose synthetase and of UDP-glucose pyrophosphorylase found in dark-grown
      hypocotyls begin to decline about 4 hours after exposure to light at a rate of
      50% every 3 hours.The data suggest that sucrose-phosphate synthetase and sucrose
      phosphatase are the enzymes responsible for the biosynthesis of sucrose from
      photosynthetically fixed CO(2), and that the major function of sucrose synthetase
      is to catalyze the synthesis of UDP-, ADP-, dTDP-, CDP-, and GDP-glucose from
      translocated sucrose in nonphotosynthetic tissues; in photosynthetic tissues the
      pyrophosphorylases may replace sucrose synthetase in catalyzing the synthesis of
      these nucleoside diphosphate glucoses. We offer the suggestion that sucrose
      synthetase and UDP-glucose pyrophosphorylase play a major role in the uptake and
      metabolism of sucrose in nonphotosynthetic tissues. Results are presented from
      preliminary studies on the conversion in vitro of sucrose to glucose 1-phosphate
      by the coupled reactions of sucrose synthetase and UDP-glucose pyrophosphorylase
      with highly purified preparations of these enzymes.

PMID- 16657392
TI  - Active H Efflux from Cells of Low-salt Barley Roots during Salt Accumulation.
AB  - Measurements were made of net H(+) loss from low-salt barley roots accumulating
      salt. Comparison of rates of loss from roots in different concentrations of KCl
      showed that H(+) loss increased in the same way as the Mechanism II component of
      salt uptake. This H(+) loss appeared to be coupled to salt uptake and was not due
      to increased respiration or metabolic breakdown of sugars. In view of the large
      negative potential of the cells (-60 millivolts), it is suggested that the H(+)
      loss is due to an outward proton transport process.

PMID- 16657393
TI  - In vivo incorporation of radioactive metabolites by Golgi apparatus and other
      cell fractions of onion stem.
AB  - Incorporation in vivo of various (14)C-labeled substrates into dictyosomes of
      onion (Allium cepa) stem was determined, and comparisons were made with other
      cell fractions on a nitrogen basis. Tissue explants were incubated for varying
      times in the presence of the radioactive metabolites supplied in the external
      medium. Fractions were then obtained from homogenates stabilized with
      glutaraldehyde. Purified fractions containing dictyosomes (individual stacks of
      cisternae) of the Golgi apparatus were obtained by centrifugation in a sucrose
      gradient also yielding a smooth membrane fraction free of dictyosomes.
      Dictyosomes were preferentially labeled with choline-1,2-(14)C and acetate-2
      (14)C, suggesting that plant Golgi apparatus participate in the synthesis or
      modification of membrane lipids. Dictyosomes were also labeled with glucose-U
      (14)C and leucine-U-(14)C, but on a molar basis incorporation was less than with
      choline or acetate.

PMID- 16657394
TI  - Lecithin Biosynthetic Enzymes of Onion Stem and the Distribution of
      Phosphorylcholine-Cytidyl Transferase among Cell Fractions.
AB  - Enzymatic activities of the cytidine 5'-diphosphate choline pathway for lecithin
      biosynthesis were demonstrated in homogenates of onion stem (Allium cepa).
      Choline kinase activity was present in the postmicrosomal supernatant, with less
      than 3% sedimenting with the particulate fractions. Phosphorylcholine-cytidyl
      transferase was distributed among all fractions, and phosphorylcholine-glyceride
      transferase was predominantly found in the particulate fraction.The
      phosphorylcholine-cytidyl transferase activity of onion stem required a divalent
      ion (Mg(2+) or Mn(2+)) for activity, was inhibited by Ca(2+), and was specific
      for cytidine triphosphate, with optimal activity in the range pH 6 to 7. To
      evaluate the distribution among cell fractions, conditions of pH, cofactors,
      substrate, and assay were optimized for each fraction. One-third of the
      transferase activity sedimented with the mitochondria-proplastids fraction, and
      one-third was in the microsomal supernatant. The dictyosome fraction contained
      about 10% of the total activity but showed a greater specific activity than the
      other fractions. Similar results were obtained with homogenates from rat liver,
      in that purified Golgi apparatus fractions contained the highest
      phosphorylcholine-cytidyl transferase activity on a protein basis when compared
      with other cell fractions at pH 7.2.

PMID- 16657395
TI  - Kinetics of Phytochrome Phototransformation: A Re-examination.

PMID- 16657396
TI  - Chloroplast Development in 4-Chloro-5-(dimethylamino)-2-(alpha,alpha,alpha
      trifluoro-m-tolyl)-3 (2H)-pyridazinone (Sandoz 6706)-treated Wheat Seedlings: A
      Pigment, Ultrastructural, and Ultracentrifugal Study.

PMID- 16657397
TI  - The photosynthetic action spectrum of the bean plant.
AB  - The photosynthetic action spectrum of the bean plant leaf, Phaseolus vulgaris L.
      (variety Red Kidney), has been determined with a diffraction grating illuminated
      by a 6500-watt xenon arc. An infrared CO(2) analyzer was used to determine the
      gross photosynthetic rate of the terminal leaflet of the first trifoliate leaf.
      The rate was measured as a function of the light intensity at steps of 12.5
      nanometers which approximates the length of the leaflet used. Twenty-five curves
      between 400 and 700 nanometers were used to establish the action spectrum. All
      light curves were some linear function of the incident intensity, and all were
      extrapolated to zero. The action spectrum shows the following features. (a) there
      are two peaks (i.e., at about 670 and 630 nanometers) and a shoulder between 600
      and 612 nanometers in the red region where the highest rate of photosynthesis is
      found. Lower peaks in descending order are found in the blue (at about 437
      nanometers) and the green (at about 500 nanometers) regions. (b) There are two
      small minima at about 650 nanometers and between 470 and 480 nanometers, and a
      broad minimum is found between 540 and 530 nanometers. (c) The photosynthetic
      rate declines rapidly above 680 nanometers, reaching the lowest value at 700
      nanometers. (d) At wave lengths below the blue maximum, the rate decreases
      progressively to 400 nanometers.

PMID- 16657398
TI  - Glutathione conjugation: atrazine detoxication mechanism in corn.
AB  - Glutathione conjugation (GS-atrazine) of the herbicide, 2-chloro-4-ethylamino-6
      isopropylamino-s-triazine (atrazine) is another major detoxication mechanism in
      leaf tissue of corn (Zea mays, L.). The identification of GS-atrazine is the
      first example of glutathione conjugation as a biotransformation mechanism of a
      pesticide in plants. Recovery of atrazine-inhibited photosynthesis was
      accompanied by a rapid conversion of atrazine to GS-atrazine when the herbicide
      was introduced directly into leaf tissue. N-De-alkylation pathway is relatively
      inactive in both roots and shoots. The nonenzymatic detoxication of atrazine to
      hydroxyatrazine is negligible in leaf tissue. The hydroxylation pathway
      contributed significantly to the total detoxication of atrazine only when the
      herbicide was introduced into the plant through the roots. The metabolism of
      atrazine to GS-atrazine may be the primary factor in the resistance of corn to
      atrazine.

PMID- 16657399
TI  - Respiration and Protein Synthesis in Dormant and After-ripened Seeds of Avena
      fatua.
AB  - Dormant seeds of Avena fatua, which do not germinate when allowed to imbibe
      water, have a respiration rate only about 20% less than that of imbibed
      nondormant (after-ripened) seeds in the period before actual germination and are
      capable of synthesizing protein at a rate comparable to that of the nondormant
      seeds. An increase of protein synthesis is observed in nondormant seeds at the
      beginning of root protrusion. Autoradiography of seeds administered (3)H-leucine
      shows that protein synthesis occurs in the axis part of the embryo, the
      scutellum, the coleorhiza, and the aleurone layer. Dormancy in seeds is not a
      state of general inactivity; rather, it must be due to some specific metabolic
      block.

PMID- 16657400
TI  - Modification of logarithmic growth rates of tobacco callus tissue by gibberellic
      Acid.
AB  - Logarithmic growth rates (either fresh or dry weight basis) of tobacco callus
      tissues grown on 10(-4) to 10(-1) mum cytokinin are increased if gibberellic acid
      (10(-3)-2 mum) is incorporated into the medium. At higher (1-10 mum) cytokinin
      concentrations gibberellic acid has little effect on growth rate but extends the
      duration of logarithmic growth. The gibberellic acid effect is noticeable only
      after one weight doubling, is dependent on concentration, and occurs when either
      glucose or sucrose is used as carbon source. The gibberellic acid response
      includes a decrease in percentage of dry weight relative to control tissues. The
      maximum dry weight yield, although achieved sooner than controls, does not differ
      appreciably from yields of tissue not treated with gibberellic acid.

PMID- 16657401
TI  - Limitation of tobacco callus tissue growth by carbohydrate availability.
AB  - Growth rate, maximum dry weight yield, and carbohydrate utilization were measured
      with pith callus derived from Nicotiana tabacum L. var. Wisconsin No. 38. Maximum
      tissue dry weights increased as carbohydrate (either glucose or sucrose) in the
      medium was increased. The time at which maximum growth was obtained coincided
      with the time at which carbohydrate was exhausted from the medium. The addition
      of carbohydrate to the medium before the end of log phase growth supported that
      amount of additional growth which would have been obtained if all of the
      carbohydrate had been added to the medium prior to planting the tissue. Maximum
      obtainable dry weights at logarithmic growth rates greater than 0.16 doubling per
      day depended on the amount of carbohydrate in the medium and not on a particular
      hormonal regime.

PMID- 16657402
TI  - N-Malonyl-d-tryptophan in Apple Fruits Treated with Succinic Acid 2,2
      Dimethylhydrazide.
AB  - Fruit from Red Delicious apple trees treated with the growth retardant succinic
      acid 2,2-dimethylhydrazide contained more N-malonyl-d-tryptophan than control
      fruit. When succinic acid 2,2-dimethylhydrazide and tryptophan were injected into
      immature fruits, more N-methyl-d-tryptophan was produced than when dl-tryptophan
      was injected alone. Our results suggest that succinic acid 2,2-dimethylhydrazide
      may control fruit and vegetative growth by interfering with auxin production.

PMID- 16657403
TI  - Adenosine Diphosphate-Glucose Pyrophosphorylase Control of Starch Accumulation in
      Rust-infected Wheat Leaves.
AB  - The variation in starch content in healthy and Puccinia striiformsi-infected
      wheat leaves was measured from 5 to 15 days after inoculation. The starch content
      of diseased leaves relative to healthy leaves decreased from 5 to 9 days,
      increased from 9 to 12 days to twice that of healthy leaves, and decreased from
      12 to 15 days after inoculation. Electron micrographs of plant tissues indicated
      that the starch accumulated in the chloroplasts of host cells adjacent to fungal
      hyphae. Variations in sugar phosphates, ATP, and inorganic phosphate were
      measured during the infection process. ADP-glucose pyrophosphorylase was
      extracted and partially purified from healthy and diseased leaves. When
      proportionate concentrations of sugar phosphates and inorganic phosphate found in
      healthy and diseased leaves during the infection process were placed in the assay
      mixture, ADP-glucose pyrophosphorylase activity was similar to the pattern of
      starch accumulation and was almost the inverse of the variation observed in
      inorganic phosphate in diseased leaves during the infection process. A mechanism
      to explain the accumulation of starch is presented and discussed. This mechanism
      is based on the regulation of ADP-glucose pyrophosphorylase by changes in
      effector molecule concentrations during the infection process. Reasons for these
      changes are presented.

PMID- 16657404
TI  - The Respiratory Chain of Plant Mitochondria: VI. Flavoprotein Components of the
      Respiratory Chain of Mung Bean Mitochondria.
AB  - Redox changes of the flavoproteins of mung bean (Phaseolus aureus) mitochondria
      were measured by differential absorbance at 468 to 493 nanometers and by
      fluorescence emission above 500 nanometers excited at 436 nanometers. Four
      flavoproteins are distinguishable by the ratio of their fluorescence to
      absorbance changes, and by their requirement, or lack of it, for energy-linked
      reverse electron transport for reduction by succinate. Two flavoproteins are
      reduced by succinate in fully depleted mitochondria which lack the capacity for
      reverse electron transport. These are designated Fp(ha) and Fp(hf) and have
      fluorescence to absorbance ratios of 0 and 1.4, respectively. The two
      flavoproteins have the same half-time for oxidation, but Fp(hf) is reduced more
      slowly than Fp(ha) by substrate in the presence of cyanide. One flavoprotein with
      a fluorescence to absorbance ratio of 0 is not reduced by succinate in anaerobic,
      fully depleted mitochondria, but is rapidly reduced on subsequent addition of
      malate; it is designated Fp(m). The fourth distinguishable flavoprotein component
      is reducible by succinate in an energy-linked reaction, even in partially
      depleted mitochondria. This component has a fluorescence to absorbance ratio of
      3.8 and is designated Fp(1f). In addition to these four flavoproteins reducible
      by substrates, there is a highly fluorescent flavin-containing component in or
      associated with these mitochondria, which is rapidly reduced by dithionite.

PMID- 16657405
TI  - In Vitro Protein Synthesis by Plastids of Phaseolus vulgaris: V. Incorporation of
      C-Leucine into a Protein Fraction Containing Ribulose 1,5-Diphosphate
      Carboxylase.
AB  - A crude chloroplast preparation of primary leaves of Phaseolus vulgaris was
      allowed to incorporate (14)C-leucine into protein. A chloroplast extract was
      prepared and purified for ribulose 1,5-diphosphate carboxylase by ammonium
      sulfate precipitation, chromatography on Sephadex G-200, and chromatography on
      Sepharose 4B. The distribution of radioactive protein and enzyme in fractions
      eluted from Sepharose 4B was nearly the same. The radioactivity in the product
      was in peptide linkage, since it was digested to a trichloroacetic acid-soluble
      product by Pronase. Whole cells in the plastid preparation were not involved in
      the incorporation of amino acid into the fraction containing ribulose 1,5
      diphosphate carboxylase, since incorporation still occurred after removal of
      cells. The incorporation into the fraction containing ribulose 1,5-diphosphate
      carboxylase occurs on ribosomes of plastids, since this incorporation is
      inhibited by chloramphenicol. These plastid preparations may be incorporating
      amino acid into ribulose 1,5-diphosphate carboxylase, but the results are not
      conclusive on this point.

PMID- 16657406
TI  - Ribonuclease Activity in Normal, opaque-2, and floury-2 Maize Endosperm during
      Development.
AB  - The elevated ribonuclease activity produced in the endosperm of a maize (Zea mays
      L.) inbred, W64A, by homozygous opaque-2, results from a more than doubled rate
      of ribonuclease accumulation occurring prior to 16 days post-pollination; after
      16 days the rates in opaque-2 and normal are the same, suggesting that opaque-2
      is no longer active. The pattern of ribonuclease increase in the opaque-2 dosage
      series indicates that opaque-2 is not fully recessive. Ribonuclease accumulation
      is not affected by floury-2 in a second inbred, B14. The results are discussed
      with reference to other proteins, notably zein, the net synthesis of which is
      affected by opaque-2.

PMID- 16657407
TI  - Water potential components in growing citrus fruits.
AB  - Growing navel orange fruits (Citrus sinensis) 5.4 to 5.7 centimeters in diameter
      were used as a model system to determine the effects of transpiration and
      carbohydrate translocation on water and osmotic potentials in fruit tissues.
      Evidence supported the hypothesis that osmotic potential in the vesicles would be
      affected little by changes in transpiration or carbohydrate translocation because
      the vesicles are anatomically isolated from the transpiration stream and are at
      the end of the carbohydrate translocation pathway. In the mesocarp tissue, which
      contains a vascular network, osmotic potential decreased during the daytime when
      environmental conditions favored transpiration and increased at night. Exocarp
      water potential followed a similar pattern. Girdling of the stem above the fruits
      5 days before sampling caused an increase of osmotic potential in the mesocarp
      but had no effect on exocarp water potential. Neither diurnal changes in
      transpiration nor girdling of the stem affected the osmotic potential of the
      vesicles.Osmotic potentials in all tissues of the fruit were in the range of -10
      to -15 bars. Measurements of osmotic potential at 16 locations along a
      longitudinal plant through the fruit axis showed that osmotic potential increased
      from the stem to the stylar end, but it decreased from the pericarp tissues to
      the vesicles. As exocarp water potential decreased during a 20-day period after
      watering, osmotic potential decreased in the vesicles and exocarp. Turgor
      pressure, calculated as the difference between water and osmotic potentials,
      decreased with water potential in the vesicles but not in the exocarp. The lack
      of decrease of turgor pressure in the exocarp may result from a measurement error
      caused by pectins or from osmotic adjustment related to carbohydrate accumulation
      at low water potentials.

PMID- 16657408
TI  - The Composition of Stigmatic Exudate from Lilium longiflorum: Labeling Studies
      with Myo-inositol, d-Glucose, and l-Proline.
AB  - Stigmatic exudate, a secretion product recovered from the upper surface of Lilium
      longiflorum pistils, has been examined. Over 99% of the exudate is accounted for
      as water, carbohydrate, and protein. Exclusive of water, 95% is a high molecular
      weight, protein-containing polysaccharide composed of galactose, arabinose,
      rhamnose, glucuronic acid, and galacturonic acid.Detached pistils supplied with
      myo-inositol-U-(14)C, myo-inositol-2-(3)H, d-glucose-1-(14)C, or l-proline-U
      (14)C produce labeled stigmatic exudate. When myo-inositol is supplied, the
      exudate is rich in labeled arabinose and uronic acids, but some label also
      recycles through the hexose phosphate pool of secreting cells, causing label to
      appear in galactose and rhamnose residues. When glucose is provided, galactose is
      the major constituent labeled but all of the other carbohydrate constituents are
      also labeled. Proline produces a pattern very similar to that obtained with
      glucose.Stigmatic exudate also contains a small amount of low molecular weight
      carbohydrate. If myo-inositol is used to label exudate, free labeled myo-inositol
      cannot be detected in the low molecular weight fraction until it has been
      subjected to acid hydrolysis. Similarly, if d-glucose is the source of label,
      free labeled glucose is found in the low molecular weight fraction only after
      acid hydrolysis.

PMID- 16657409
TI  - Effect of ethylene on the uptake, distribution, and metabolism of indoleacetic
      Acid-1-C and -2-C and naphthaleneacetic Acid-1-C.
AB  - The effect of ethylene on the uptake, distribution, and metabolism of
      indoleacetic acid (IAA)-1-(14)C, IAA-2-(14)C, and naphthaleneacetic acid (NAA)-1
      (14)C in cotton stem sections (Gossypium hirsutum L., var. Stoneville 213) was
      studied. Stem sections excised from plants pretreated with ethylene for 15 hours
      transported significantly less (14)C-IAA and (14)C-NAA than control sections.
      Concomitant features of the reduction of (14)C-IAA transport were an increase in
      decarboxylation and a trend toward a reduction in total uptake. With (14)C-NAA,
      however, total uptake was significantly increased, and decarboxylation was
      unaffected.(14)C-IAA was rapidly converted to indoleacetylaspartic acid and many
      other metabolites in both control and ethylene-pretreated stem sections.
      Following transport, similar amounts of (14)C-IAA were recovered in the apical
      absorbing portion of the control and ethylene-pretreated sections. Significantly
      more (14)C-IAA metabolites, however, were recovered in this region of the
      ethylene-pretreated sections.Conversely, (14)C-NAA was metabolized more slowly
      than (14)C-IAA under identical experimental conditions, with the only major
      metabolite being naphthaleneacetylaspartic acid. Following transport the apical
      absorbing portion of ethylene-pretreated stem sections contained significantly
      more (14)C-NAA than the controls. These results suggested that the disruption of
      auxin transport by ethylene cannot be explained in terms of a more rapid
      metabolism of auxin in the treated sections. The increased (14)C-IAA metabolites
      in the absorbing portion of ethylene-pretreated sections appear to be the result,
      rather than the cause, of the ethylene-mediated disruption of IAA transport.

PMID- 16657410
TI  - Energy and Electron Transfer Systems of Chlamydomonas reinhardi: II. Two Cyclic
      Pathways of Photosynthetic Electron Transfer in the Pale Green Mutant.
AB  - Light- and oxygen-induced changes of cytochromes f, b(563), and b(559) and
      ferredoxin-flavoprotein were studied by a double beam spectrophotometer with
      combinations of inhibitors and lowered temperatures in the whole cells of the
      pale green mutant of Chlamydomonas reinhardi (ATCC 18302). At room temperature,
      the steady state changes of cytochrome f and ferredoxin-flavoprotein are small,
      but at low temperature slightly above 0 C, they are clearly defined.
      Phenylmercuric acetate inhibits photoreduction of ferredoxin-flavoprotein and
      cytochrome f simultaneously but not that of cytochrome b(563). 2-Heptyl-4
      hydroxyquinoline-N-oxide shows a crossover point between cytochromes f and b(563)
      and partially inhibits photoreduction of cytochrome f. Two cyclic pathways
      operating in C. remhardi are postulated: (a) photosystem I --> x --> b(563) --> f
      --> photosystem I; and (b) photosystem I --> x --> ferredoxin-flavoprotein --> f 
      -> photosystem I.

PMID- 16657411
TI  - Abscisic Acid and transpiration in leaves in relation to osmotic root stress.

PMID- 16657412
TI  - Induction of peroxidase activity by ethylene in sweet potato.

PMID- 16657413
TI  - Analysis of operation and calibration of a ventilated diffusion porometer.

PMID- 16657414
TI  - The constancy of the buoyant density of chloroplast and mitochondrial
      deoxyribonucleic acids in a range of higher plants.

PMID- 16657415
TI  - Effects of guanidine inhibitors on mung bean mitochondria.
AB  - The effects of phenylethylbiguanidide, decamethylenediguanidide, and
      octylguanidine have been studied with mung bean hypocotyl mitochondria (Phaseolus
      aureus var. Jumbo) supplied with malate, reduced nicotinamide adenine
      dinucleotide, succinate, or ascorbate-tetramethyl-p-phenylenediamine as
      substrates. The guanidines act as energy transfer inhibitors, all three
      inhibiting all three phosphorylation sites. Phenylethylbiguanidide causes only
      partial inhibition even at relatively high concentrations.
      Decamethylenediguanidide inhibits about 70% of the malate respiration, 55% of the
      succinate respiration, and 35% of the ascorbate-tetramethyl-p-phenylenediamine
      respiration.Octylguanidine inhibits all three phosphorylation sites and the
      cyanide-insensitive respiration, but to differing extents and at different
      concentrations. Both states 3 and 4 are inhibited by octylguanidine. Inhibition
      of state 4 is preceded by an uncoupling action at lower concentrations of
      inhibitor, while inhibition of state 3 is influenced by the state of the
      mitochondria when the inhibitor is added. Application of the guanidine to state 4
      mitochondria is more effective than application to mitochondria already in state
      3.

PMID- 16657416
TI  - Preparation and some properties of submitochondrial particles from tightly
      coupled mung bean mitochondria.
AB  - Osmotic shock was found to be better than freezing and thawing, a French press,
      or sonic oscillation for the preparation of submitochondrial particles from mung
      bean (Phaseolus aureus) hypocotyl mitochondria. Particles prepared by osmotic
      shock rapidly oxidize reduced nicotinamide adenine dinucleotide and succinate,
      but they oxidize malate slowly. NADH oxidation was slightly stimulated by
      cytochrome c, ATP, and ADP; succinate oxidation was markedly increased by ATP,
      slightly by ADP and cytochrome c; and malate oxidation required the addition of
      NAD(+) NADH oxidation is inhibited weakly by amytal, completely by antimycin A
      and KCN, but not by rotenone. Chlorsuccinate, malonate, antimycin A, and KCN
      inhibit succinate oxidation. The action of antimycin A and KCN is incomplete,
      while chlorsuccinate and malonate were competitive inhibitors. Antimycin A
      combined stoichiometrically with particle protein in the ratio of 0.23
      millimicromole per milligram of protein.Oligomycin and bis(hexafluoroacetonitryl)
      acetone, a potent uncoupler of oxidative phosphorylation, were without effect on
      oxygen uptake but did influence the ATP-stimulated onset of respiration when
      succinate was substrate. Fresh particles were markedly inhibited by
      oxtylguanidine, indicating energy conservation, but this inhibition decreased on
      storage of the particles.Spectra show the presence of cytochrome components the
      same as those of the intact mung bean mitochondrion, but present at higher
      concentrations. The molar concentrations of the particle cytochromes were two to
      three times those of the intact mitochondrion and the molar ratios were
      calculated as 0.9:1.0:1.0:2.8 for cytochromes a:b:c:flavoprotein, respectively.

PMID- 16657417
TI  - Energy-linked Functions of Submitochondrial Particles Prepared from Mung Bean
      Mitochondria.
AB  - Submitochondrial particles from mung bean mitochondria (Phaseolus aureus) are
      able to catalyze an energy-linked reduced nicotinamide adenine dinucleotide
      nicotinamide adenine dinucleotide phosphate transhydrogenase reaction supported
      by ATP or by aerobically generated high energy intermediates. The energy transfer
      pathway appears to differ from that utilized for oxidative phosphorylation.Mung
      bean submitochondrial particles will also reduce nicotinamide adenine
      dinucleotide by reversed electron transport from succinate or ascorbate
      tetramethyl-p-phenylenediamine. The energy requirement can be met by ATP or by
      aerobically generated high energy intermediates.A scheme for the energy
      transduction pathway in mung beans is postulated from the effects of inhibitors
      and uncouplers of energy transfer on transhydrogenase and reversed electron
      transfer reactions.

PMID- 16657418
TI  - A Lack of Specificity for Ethylene-induced Mitochondrial Changes.
AB  - A critical evaluation was made of the hypothesis that the primary mode of action
      of ethylene in inducing physiological responses is by changing the permeability
      of cell organelles. The parameter investigated was the evaluation of the
      influence of ethylene and other gases on mitochondrial oxidation and swelling.
      Spectrometric evidence demonstrated that mitochondria prepared with good
      respiratory control can be induced to swell more rapidly with ethylene and other
      aliphatic gases (ethane, propene, propane, I-butene) in test solutions of 0.125 m
      KCl. The fact that saturated as well as unsaturated hydrocarbon gases elicited
      similar changes provides evidence that ethylene does not directly alter membrane
      permeability as its mechanism of action.

PMID- 16657419
TI  - Changes in the Respiratory, Enzymatic, and Swelling and Contraction Properties of
      Mitochondria from Colytedons of Phaseolus vulgaris L. during Germination.
AB  - Mitochondria isolated from cotyledons of germinating wax beans (Phaseolus
      vulgaris L.) showed fairly good respiratory control on days 1 and 2 after
      planting. The respiratory control was completely lost from days 3 to 5. During
      this period mitochondria were shown to be very leaky, losing about 88% of their
      total nicotinamide adenine dinucleotide to the suspending medium in a short time.
      The respiratory control was partially recovered by day 7, after which it
      completely disappeared again. By the use of differential centrifugation, the
      mitochondria were divided into subfractions by sequential centrifugation: 10,000g
      for 5 minutes, 25,000g for 5 minutes, and 40,000g for 5 minutes. The 10,000g
      subfraction was responsible for the recovery of mitochondrial activity
      (respiratory control value, adenosine diphosphate to oxygen ratio, and rate of
      oxygen utilization), on day 7. Activities of succinate dehydrogenase, cytochrome
      oxidase, pyruvate dehydrogenase, and isocitrate dehydrogenase from different
      mitochondrial subfractions of aging cotyledons were determined. In general, the
      enzyme activities, adenosine diphosphate to oxygen ratios, and the ability of
      mitochondria to swell and contract followed the same pattern as for respiratory
      control.

PMID- 16657420
TI  - Phloem mobility of magnesium.
AB  - Magnesium-28 was applied to specific leaves of bean (Phaseolus vulgaris) and
      barley (Hordeum vulgare) plants. After 24 hours, as much as 7% of the absorbed Mg
      was exported from the treated bean leaves and 11% was transported basipetally
      from the treated zone of the barley leaves. Transport of Mg did not occur past a
      heat-killed section of the treated leaf, thereby indicating that translocation
      took place via the phloem. Mg movement in the phloem was also evident in
      autoradiograms of bean stem segments in which the xylem was separated from the
      phloem by a thin sheet of plastic.

PMID- 16657421
TI  - Stimulation of Solute Loss from Radicles of Gossypium hirsutum L. by Chilling,
      Anaerobiosis, and Low pH.
AB  - The loss of organic substances from cotton (Gossypium hirsutum L.) radicles is
      enhanced by chilling, low pH, or anaerobic conditions. Solute loss returns to a
      low level when the stimulus is removed, indicating no permanent injury to
      membranes. Loss of solute induced by chilling or anaerobiosis is reversed or
      prevented by calcium or magnesium. These cations did not reduce the solute loss
      resulting from low pH. The site of loss appears to be localized at or near the
      root tip. If the seedling cotyledons are removed, the loss is greatly reduced,
      indicating the need for a reserve pool of organic substances.

PMID- 16657422
TI  - Photochlorophyll Biosynthesis in Cucumber (Cucumis sativus, L.) Cotyledons.
AB  - The formation of protochlorophyllide and protochlorophyllide phytyl ester was
      investigated during etioplast biogenesis in order to study the biosynthetic
      relation of these two compounds. Protochlorophyllide accumulates slowly during
      the first 2 days of germination, its rate of formation increases sharply during
      the 3rd day, and then it decreases. Protochlorophyllide phytyl ester starts
      accumulating a day later; its formation coincides with the initiation of
      xanthophyll biosynthesis. Kinetic analysis of specific radioactivities after
      (14)C labeling of the protochlorophyll pools does not support the currently
      accepted conversion of protochlorophyllide into protochlorophyllide phytyl ester,
      but suggests that both compounds originate simultaneously from a common precursor
      pool.

PMID- 16657423
TI  - Variability in Complementarity for Chloroplastic and Cytoplasmic Ribosomal
      Ribonucleic Acid among Plant Nuclear Deoxyribonucleic Acids.
AB  - The nuclear DNAs from a number of angiosperm species were tested for
      hybridization to the RNAs contained in 70 S (chloroplastic) and 80 S
      (cytoplasmic) ribosomes. All of the DNAs contained regions complementary to RNAs
      from chloroplastic as well as cytoplasmic ribosomes. DNAs from closely related
      plants varied widely in their proportion of coding for these RNAs. About 0.15% of
      the DNAs from a number of different species of Nicotiana were found to be
      complementary to the RNAs of each kind of ribosome; however, DNAs from some other
      members of this genus had more than three times this proportion of coding for
      ribosomal RNAs. These and other data suggest that hybridization percentage for
      ribosomal RNA is not a familial or generic characteristic.DNAs with high amounts
      of coding for ribosomal RNAs have thus far been found to contain satellite DNAs
      of base composition more like ribosomal RNA than the main DNA component. The
      satellite DNA from pumpkin has been isolated and shown to contain cistrons for
      both chloroplastic and cytoplasmic ribosomal RNAs.

PMID- 16657424
TI  - The time course of xylem differentiation and its relation to deoxyribonucleic
      Acid synthesis in cultured coleus stem segments.
AB  - The relationship between DNA synthesis and wound xylem differentiation was
      investigated in cultured stem segments of Coleus blumei. The addition of 50
      micrograms of indoleacetic acid per liter to the culture medium resulted in a 400
      to 500% increase in the number of wound vessel members formed in 7 days. However,
      the time course of wound vessel member formation was similar in segments cultured
      in the presence and absence of auxin. In either case, no wound vessel members
      appeared before the 3rd day of culture, while the majority of wound vessel
      members appeared on the 4th and 5th days of culture. (3)H-Thymidine incorporation
      into DNA was used to measure changes in the DNA synthetic activity of the tissues
      during the culture period. Comparatively little (3)H-thymidine incorporation
      occurred during the 1st day of culture. Maximum (3)H-thymidine incorporation was
      observed on the 2nd day of culture, 2 days before the peak period of xylem
      differentiation. The rate of incorporation of (3)H-thymidine into DNA decreased
      with increasing time in culture after the 2nd day. Auxin at 50 micrograms per
      liter had no effect on the time course of (3)H-thymidine incorporation, although
      somewhat more (3)H-thymidine was incorporated into DNA throughout the culture
      period in the presence of auxin. The magnitude of this effect was small when
      compared to the effect of auxin on xylem differentiation. The antimetabolite 5
      fluorodeoxyuridine was shown to block DNA synthesis in the cultured stem
      segments. When the tissues were isolated on media containing 10(-6)m 5
      fluorodeoxyuridine, wound vessel member differentiation was inhibited by
      approximately 80%, in both the presence and absence of auxin. Thymidine at 10(
      5)m completely overcame the 5-fluorodeoxyuridine inhibition of wound vessel
      member formation. 5-Fluorodeoxyuridine was effective in blocking xylogenesis only
      when this substance was supplied to the tissues during the early part of the
      culture period. 5-Fluorodeoxyuridine had no effect on xylem differentiation when
      it was applied after the 3rd day of culture.

PMID- 16657425
TI  - Polysaccharide-degrading Enzymes are Unable to Attack Plant Cell Walls without
      Prior Action by a "Wall-modifying Enzyme".
AB  - A study of the degradation of plant cell walls by the mixture of enzymes present
      in Pectinol R-10 is described. A "wall-modifying enzyme" has been purified from
      this mixture by a combination of diethylaminoethyl cellulose, Bio Gel P-100, and
      carboxymethyl cellulose chromatography. Treatment of cell walls with the "wall
      modifying enzyme" is shown to be a necessary prerequisite to wall degradation
      catalyzed by a mixture of polysaccharide-degrading enzymes prepared from Pectinol
      R-10 or by an alpha-galactosidase secreted by the pathogenic fungus
      Colletotrichum lindemuthianum. The action of the "wall-modifying enzyme" on cell
      walls is shown to result in both a release of water-soluble, 70% ethanol
      insoluble polymers and an alteration of the residual cell wall. A purified
      preparation of the "wall-modifying enzyme" is unable to degrade a wide variety of
      polysaccharide, glycoside, and peptide substrates. However, the purified
      preparation of wall-modifying enzyme has a limited ability to degrade
      polygalacturonic acid. The fact that polygalacturonic acid inhibits the ability
      of the "wall-modifying enzyme" to affect cell walls suggests that the "wall
      modifying enzyme" may be responsible for the limited polygalacturonic acid
      degrading activity present in the purified preparation. The importance of a wall
      modifying enzyme in developmental processes and in pathogenesis is discussed.

PMID- 16657426
TI  - Polyacrylamide gel analysis of high molecular weight ribonucleic Acid from
      etiolated and green cucumber cotyledons.
AB  - Cucumis sativus L. seeds and 5-day-old dark-grown cotyledons contain 25 and 18 S
      cytoplasmic ribosomal RNAs as main components. The major increase in nucleic acid
      content in both green and etiolated cotyledons occurs between days 5 and 7 of
      germination. This increase is characterized by an important synthesis of 23 and
      16 S plastid (chloroplast and proplastid) ribosomal RNAs. Proplastid RNA
      synthesis appears to continue for a longer period in the dark-grown cotyledons,
      despite a total RNA content considerably less than in the light-grown
      cotyledons.The nonribosomal distribution of the chloroplast and proplastid
      ribosomal RNAs observed in all cases (after extraction and fractionation) results
      from the lability of the 23 S component. This degradation increases if the
      chloroplasts and proplastids are isolated prior to extraction of their nucleic
      acid.

PMID- 16657427
TI  - The relation of the 515 nanometers absorbance change to adenosine triphosphate
      formation in chloroplasts and digitonin subchloroplast particles.
AB  - The flash-induced absorbance changes at 515 nanometers has been studied in
      chloroplasts and in digitonin subchloroplast particles of lettuce. The effect of
      various conditions and uncouplers was tested on the decay kinetics of this
      absorbance change and on ATP formation in the presence of phenazine
      methosulphate, either by continuous or flash illumination. It has been found that
      in chloroplasts, carbonyl cyanide m-chloromethoxyphenylhydrazone and nigericin in
      the presence of K(+) accelerate the decay of the 515 change and inhibit ATP
      formation. However, under a variety of conditions the rate of decay of the 515
      absorbance change was found to be unrelated to ATP formation. Preillumination,
      addition of valinomycin in the presence of K(+), addition of Na(+), or divalent
      cations accelerate the decay of the 515 absorbance change markedly but have no
      effect on ATP formation. Addition of phosphorylation reagents has no effect on
      the decay rate beyond that obtained by Mg(2+) and inorganic phosphate. NH(4)Cl,
      and to some extent atebrin, while inhibiting ATP formation, do not affect the
      decay of the 515 absorbance change.In digitonin subchloroplast particles the
      decay kinetics of the absorbance change resemble that of chloroplasts, but the
      magnitude of the change is smaller. The pH change in this preparation is reduced
      much more than the 515 absorbance change.According to the chemiosmotic
      hypothesis, the sum of DeltaE(membrane potential) and DeltapH is the driving
      force for ATP formation. The lack of an increase in DeltaE in digitonin
      subchloroplast particles, which are practically devoid of DeltapH and have a
      normal ATP-forming activity, is inconsistent with the chemiosmotic hypothesis.

PMID- 16657428
TI  - Influence of calcium on sodium and potassium absorption by fresh and aged bean
      stem slices.
AB  - The influence of Ca on the aging processes of bean stem (Phaseolus vulgaris)
      slices and on the absorption of K and Na by fresh and aged slices was
      investigated. In the presence of Ca, fresh tissue showed a preferential Na
      uptake. The preference for Na over K resulted from a differential depressive
      effect of Ca on absorption of these two ions. In aged tissue Na uptake was also
      depressed, but K absorption was accelerated, with a net result of a much greater
      absorption of K than Na.The presence of Ca in the aging medium promoted the
      development of K-absorbing capacity as well as an increase in the rate of
      respiration but did not influence the loss of capacity to absorb Na as tissue
      aged. This, along with the demonstration that protein synthesis is involved in
      the development of K-absorbing capacity by aging tissue, suggests that Ca may
      have an effect on basic physiological processes concerned with development of ion
      absorption by aging tissue. The influences that Ca may have on the physical and
      physiological aspects of ion transport are discussed.

PMID- 16657429
TI  - Circadian Rhythm of Leaves of Phaseolus angularis Plants Grown in a Controlled
      Carbon Dioxide and Humidity Environment.
AB  - Leaf movements of primary leaves of Phaseolus angularis Wight. were studied in an
      environment with controlled levels of CO(2), relative humidity, temperature,
      light, nutrient concentrations, and water tension. Rhythmic circadian movements
      and irregular short period movements were evident as the leaves unfolded and
      persisted during development of the leaves. The mean period in rhythmic circadian
      movement was 27.3 hours with no significant differences in period between plants
      of the same or different experiments. The leaf movements of separate plants were
      not closely synchronized.A system is described for growing plants for extended
      periods while collecting data with time lapse photography. The system was
      developed to minimize disturbances to the plants.The occurrence of leaf movements
      in plants grown from the time of seeding in an environment free of any recognized
      fluctuation which could stimulate leaf movements supports the hypothesis that
      leaf movement rhythms originate spontaneously within the plant.

PMID- 16657430
TI  - Observations on the mechanism of copper damage in chlorella.
AB  - Addition of excess copper to nongrowing cells of a normal, green Chlorella caused
      a reduction in total pigments and a blue shift of chlorophyll absorption,
      concurrent with the inhibition of photosynthesis. Chlorophylless yellow and white
      mutant strains of the same alga showed a rise in nonspecific absorption (i.e.,
      change in light scatter) within 5 to 10 minutes after the addition of CuSO(4);
      concomitantly a lowering of packed cell volume and a rise in respiration
      occurred. Glutathione prevented all copper-induced changes, whereas MnCl(2)
      protected only partially. Selective inhibition of some responses to copper was
      observed when O(2) was absent or an antioxidant present.

PMID- 16657431
TI  - Time course of auxin stimulations of growth.
AB  - Measurements of the time course of growth responses of corn coleoptile sections
      to pulses of auxin (10(-5)m indoleacetic acid) establish that the growth rate
      changes in a regular pattern around the auxin pulse: a latent phase of 12 to 15
      minutes is followed by an acceleration of growth rate lasting 15 to 20 minutes,
      after which a fairly steady rate is maintained. When the auxin source is
      withdrawn, there is an after-effect of about 15 minutes followed by a decay of
      growth rate, which reaches 50% decay after a further 15 to 40 minutes. The decay
      phase appears to be a function of the transport of auxin out of the sections. The
      50% decay of growth for single cells is estimated at 30 minutes from the time of
      withdrawal of an exogenous supply of auxin. The regulation of growth by auxin is
      rapidly imposed or dissipated as auxin enters and exits, respectively, suggesting
      a facile association and disassociation of auxin with a growth-limiting site in
      the cell. It is proposed that the growth-stimulated state is dissipated at once
      when the transportable auxin has passed out of the cell.

PMID- 16657432
TI  - A thermistor leaf thermometer.
AB  - An instrument is described which allows measurements of leaf temperature within
      about 0.3 C. It consists of a special thermistor probe, a small circuit box, and
      a standard ammeter. The circuit box can easily be fixed to the meter and contains
      a battery, which passes 0.3 milliampere through the thermistor, and also contains
      an integrated circuit amplifier, so that the meter reads 20 C full scale
      deflection, with ranges adjustable in 10 C steps. Calibration experiments show
      the superiority of the thermistor leaf thermometer to a thermocouple pressed onto
      a rubber surface with a resilience resembling that of a leaf.

PMID- 16657433
TI  - Synthesis of Cellulase during Abscission of Phaseolus vulgaris Leaf Explants.
AB  - When abscission in leaf explants from Phaseolus vulgaris, cultivar Red Kidney,
      was allowed to proceed while the explants were in (2)H(2)O, a 1.25% increase in
      the buoyant density of cellulase in a cesium chloride gradient was observed.
      These data indicate that the increase in cellulase activity during abscission is
      a result of the synthesis of new protein. Two differentially soluble forms of
      cellulase are present in the abscission zone. The form which is soluble only in a
      high salt buffer seems more closely related to the abscission process than the
      form which is soluble in dilute buffer. The correlation between changes in pull
      force and increase in cellulase activity and the effects of several hormones on
      cellulase activity are discussed.

PMID- 16657434
TI  - Freezing damage to isolated tomato fruit mitochondria as modified by
      cryoprotective agents and storage temperature.
AB  - Isolated tomato (Lycopersicon esculentum var. Kc 146) fruit mitochondria could be
      stored successfully in the frozen state without a cryoprotective agent if the
      mitochondria were frozen quickly by immersion in liquid nitrogen and later thawed
      quickly at 30 C. Criteria of freezing damage were rate of respiration, adenosine
      diphosphate to oxygen ratio, and respiratory control ratio. Marked reduction in
      respiration and loss of respiratory control occurred when mitochondria were
      transferred from liquid nitrogen to -5, -10, or -18 C for 15 minutes prior to
      thawing at 30 C. Dimethylsulfoxide (5%) prevented freezing damage when
      mitochondria were incubated at -5 C but did not prevent freezing damage at -10 or
      -18 C. Isolated tomato mitochondria show promise as a model system for studying
      the nature of freezing damage and the mode of action of cryo-protective agents.

PMID- 16657435
TI  - A simplified purification and some properties of ribulose 1,5-diphosphate
      carboxylase from barley.
AB  - A rapid procedure was developed for purifying ribulose 1,5-diphosphate
      carboxylase from barley leaves. After (NH(4))(2)SO(4) fractionation, the unique
      sedimentation properties of the enzyme were exploited to effect a single step
      purification to 90% homogeneity. High speed centrifugation pelleted the enzyme
      with complete recovery of activity. Residual impurities were then removed by
      diethylaminoethyl cellulose chromatography and density gradient centrifugation.
      The purified protein exhibited size heterogeneity due to polymerization. The
      polymerization products were enzymatically active aggregates of ribulose 1,5
      diphosphate carboxylase and were precipitated by an antibody specific for the
      enzyme.

PMID- 16657436
TI  - Senescense: association of synthesis of Acid phosphatase with banana ripening.
AB  - During ripening of banana (Musa sapientum L., var. Gros Michel or Valery) acid
      phosphatase activity increases 13-to 26-fold in the precipitate and 2- to 4-fold
      in the supernatant fraction of tissue homogenates. These increases are closely
      correlated with the onset and peak of the climacteric. The precipitate enzyme may
      be extracted with Triton X-100, CaCl(2) or NaCl; about 80% of it is in a 500g
      precipitate. Studies on effect of tonicity of the grinding medium indicate that
      the precipitate enzyme is desorbed from membrane or cell wall surfaces, and is
      not released as a result of lysis of membranes. The development of acid
      phosphatase during aging of tissue slices is the same as in intact fruit. Short
      term studies of tissue slices with cycloheximide and actinomycin D indicate that
      the increase in activity is owed to new enzyme synthesis, which is dependent upon
      synthesis of RNA. The possible effects of the increase in acid phosphatase on
      ripening are discussed.

PMID- 16657437
TI  - Antagonisms between Kinetin and Amino Acids: Experiments on the Mode of Action of
      Cytokinins.
AB  - The maintenance of chlorophyll in darkened first leaves of oats was used as a
      bioassay for cytokinins in pea (Pisum sativum) roots. No cytokinin was found (in
      contrast with earlier reports on sunflower roots); however, the extracts
      contained two or more substances antagonistic to cytokinin, i. e., promoting the
      yellowing in this test. Because the most active of these appeared to be an amino
      acid, individual amino acids were examined for their ability to modify the
      greening reaction. As a result, l-serine was found to have these properties. It
      promotes yellowing whether the greening agent is kinetin, indoleacetic acid, or
      adenine; it is, therefore, not functioning as a specific cytokinin antagonist.
      Its action is due to promoting proteolysis. Its d-isomer is inactive. l-Arginine,
      which alone does not cause chlorophyll retention and only weakly inhibits
      proteolysis, strongly antagonizes the action of l-serine, and thus prevents the
      yellowing; this effect is specific, and the only other effective serine
      antagonist found, although much weaker, is l-threonine. The action of arginine is
      not due to its preventing serine uptake, but rather the action parallels the
      serine-arginine antagonism previously described for nitrate reductase induction.
      A novel interpretation of the effect of amino acids on this process is therefore
      put forward. In studies of the RNase in darkened oat leaves, serine was found to
      have no effect; however, kinetin strongly inhibits the normal rise in the level
      of RNase which occurs in the isolated leaf. Kinetin also maintains the integrity
      of the cell membranes. A variety of evidence leads to the conclusion that the
      primary action of kinetin on the leaf is to inhibit proteolysis, rather than to
      promote protein synthesis.

PMID- 16657438
TI  - Increased ribonucleic Acid polymerase activity associated with chromatin from
      internodes of dwarf pea plants treated with gibberellic Acid.
AB  - Gibberellic acid increases the level of RNA polymerase associated with chromatin
      isolated from expanding internodes of light-grown, dwarf pea plants (Pisum
      sativum L.), without a detectable increase in the amount of DNA template
      available.

PMID- 16657439
TI  - Defined Media for Growth and Gamete Production by the Green Alga, Oedogonium
      cardiacum.
AB  - Defined media consisting of inorganic salts and vitamin B(12) are described for
      the male and female filaments of the green alga, Oedogonium cardiacum. These
      media provide for a maximal growth rate and for the induction of oogonia and
      antheridia under the prescribed conditions. The maximal amounts of growth, based
      on dry weight measurements, compare favorably with other green algae.

PMID- 16657440
TI  - Specificity of cycloheximide in higher plant systems.
AB  - Although cycloheximide is extremely inhibitory to protein synthesis in vivo in
      higher plants, the reported insensitivity of some plant ribosomes suggests that
      it may not invariably act at the ribosomal level. This suggestion is reinforced
      by results obtained with red beet storage tissue disks, the respiration of which
      is stimulated by cycloheximide at 1 microgram per milliliter. Inorganic ion
      uptake by these disks is inhibited by cycloheximide at 1 microgram per milliliter
      while the uptake of organic compounds, by comparison, is unaffected. Ion uptake
      by all nongreen tissues tested is inhibited by cycloheximide, but leaf tissue is
      unaffected, indicating that the ion absorption mechanism in the leaf may differ
      fundamentally from that in the root. It is concluded that cycloheximide can
      affect cellular metabolism other than by inhibiting protein synthesis and that
      the inhibition of ion uptake may be due to disruption of the energy supply.

PMID- 16657441
TI  - Leaf enlargement and metabolic rates in corn, soybean, and sunflower at various
      leaf water potentials.
AB  - Rates of photosynthesis, dark respiration, and leaf enlargement were studied in
      soil-grown corn (Zea mays), soybean (Glycine max), and sunflower (Helianthus
      annuus) plants at various leaf water potentials. As leaf water potentials
      decreased, leaf enlargement was inhibited earlier and more severely than
      photosynthesis or respiration. Except for low rates of enlargement, inhibition of
      leaf enlargement was similar in all three species, and was large when leaf water
      potentials dropped to about -4 bars.Intact sunflower leaves were held for 4 days
      at leaf water potentials which permitted maximal photosynthesis and respiration,
      but which inhibited leaf enlargement. Although leaf enlargement did not occur
      initially, enlargement resumed toward the end of the desiccation period. However,
      the rate of enlargement was not as rapid as in the well watered control, nor did
      it return to the control rate when the plant was rewatered.

PMID- 16657442
TI  - Differing sensitivity of photosynthesis to low leaf water potentials in corn and
      soybean.
AB  - Rates of net photosynthesis were studied in soil-grown corn (Zea mays) and
      soybean (Glycine max) plants having various leaf water potentials. Soybean was
      unaffected by desiccation until leaf water potentials were below -11 bars. Rates
      of photosynthesis in corn were inhibited whenever leaf water potentials dropped
      below -3.5 bars.The differences in photosynthetic behavior could be attributed
      solely to differences in stomatal behavior down to leaf water potentials of -16
      bars in soybean and -10 bars in corn. Below these potentials, other factors in
      addition to stomatal closure caused inhibition, although their effect was
      relatively small.Corn, which has the C(4)-dicarboxylic acid pathway for carbon
      fixation, generally had a higher rate of photosynthesis than soybean during
      desiccation. Nevertheless, since inhibition of photosynthesis began at higher
      potentials than in soybean, and since corn was less able to withstand severe
      desiccation without tissue death, it was concluded that the C(4) pathway confers
      no particular ability to withstand low leaf water potentials.

PMID- 16657443
TI  - Controls on chlorophyll synthesis in barley.
AB  - In 7- to 10-day-old leaves of etiolated barley (Hordeum vulgare), all of the
      enzymes that convert delta-aminolevulinic acid to chlorophyll are nonlimiting
      during the first 6 to 12 hours of illumination, even in the presence of
      inhibitors of protein synthesis. The limiting activity for chlorophyll synthesis
      appears to be a protein (or proteins) related to the synthesis of delta
      aminolevulinic acid, presumably delta-aminolevulinic acid synthetase. Protein
      synthesis in both the cytosol and plastids may be required to produce nonlimiting
      amounts of delta-aminolevulinic acid. The half-life of a limiting protein
      controlling the synthesis of delta-aminolevulinic acid appears to be about 1(1/2)
      hours, when determined with inhibitors of protein synthesis. Acceleration of
      chlorophyll synthesis by light is not inhibited by inhibitors of nucleic acid
      synthesis, but is inhibited by inhibitors of protein synthesis. A model for
      control of chlorophyll synthesis is proposed, based on a light-induced activation
      at the translational level of the synthesis of proteins forming delta
      aminolevulinic acid, as well as the short half-life of these proteins. Evidence
      is presented confirming the idea that the holochrome on which protochlorophyllide
      is photoreduced to chlorophyllide functions enzymatically.

PMID- 16657444
TI  - Photoinduced changes in the chlorophyll a to chlorophyll B ratio in young bean
      plants.
AB  - An alternating light-dark system is described under which etiolated bean
      (Phaseolus vulgaris) leaves form selectively chlorophyll a.This system consists
      of cycles of 2 minutes of white light alternating with 98-minute dark
      periods.Etiolated tissue exposed to a series of such light-dark cycles
      accumulates chlorophyll a predominantly, with no lag phase in its biosynthesis. A
      very high ratio of chlorophyll a:chlorophyll b is thus established. The ratio
      increases with the number of light exposures up to about 45 such exposures and
      then it declines. Transfer of the etiolated tissue to continuous illumination
      after a number of such light exposures results in a dramatic drop of the
      chlorophyll a:chlorophyll b ratio to values normally found in green plants.

PMID- 16657445
TI  - Enhancement of wall loosening and elongation by Acid solutions.
AB  - The ability of low pH and CO(2) to induce rapid cell elongation and wall
      loosening in the Avena coleoptile has been examined with the use of a continuous
      growth-recording technique and an Instron extensometer, respectively. In
      particular, the properties of the response to hydrogen ions have been examined in
      detail and have been compared with the responses initiated by CO(2) and auxin.
      The optimal pH for growth is about 3.0, and both the maximal growth rate and wall
      extensibility are similar to that produced by optimal auxin. The timing
      (initiated in less than 1 minute) and duration (up to 2 hours) of the response to
      hydrogen ions, as well as certain other aspects of the growth and wall-loosening
      responses, are described. It is shown that the pH response can be clearly
      separated from the CO(2) response. Possible mechanisms for the initiation of the
      growth response to low pH are briefly discussed.

PMID- 16657446
TI  - Effects of slowly permeating osmotica on metabolism of vacuolated and
      nonvacuolated tissues.
AB  - Vacuolated and nonvacuolated root tissues of Zea mays were exposed to low water
      potentials by addition of mannitol or glycerol. Temporary increases were observed
      for O(2) uptake, but CO(2) evolution remained steady. This increase in O(2)
      uptake ceased after 15 minutes. Further treatment induced decreases in
      respiration, with similar reductions in O(2) uptake and CO(2) evolution.Removal
      of osmotica from nonvacuolated tissues restored high rates of respiration, uptake
      of glucose, and synthesis of methanol-insoluble compounds. In contrast, rates of
      all these processes decreased to very low values when vacuolated tissues were
      returned to high water potentials. Deplasmolysis also induced rapid leakage of
      metabolic intermediates from vacuolated tissues, but leakage from nonvacuolated
      tissues was only slightly increased. It is suggested that these contrasting
      responses of vacuolated and nonvacuolated tissues are related to differences in
      structural changes, during either plasmolysis or deplasmolysis.

PMID- 16657447
TI  - Effects of rapidly and slowly permeating osmotica on metabolism.
AB  - Zea mays was exposed to solutions of low water potentials by addition of ethylene
      glycol or mannitol. Intact seedlings were treated for 1 hr at potentials between 
      10 and -20 atmospheres and then returned to high water potentials. Subsequent
      root extension was slow after mannitol treatment, but rapid when ethylene glycol
      had been used as the osmoticum. Cellular activity of excised roots was also
      affected much less by ethylene glycol than by mannitol. Processes studied
      included respiration, glucose uptake, and synthesis of methanol-insoluble
      compounds. These differences in response to various osmotica applied both during
      and after treatment at low water potentials.Ethylene glycol penetrated the
      tissues much more rapidly than mannitol. Rapid penetration of the osmoticum would
      minimize turgor loss and plasmolysis. Thus, the data suggest that adverse effects
      were induced by water loss or structural changes, or both, during plasmolysis,
      rather than by low water potentials, demonstrating the crucial importance of
      osmotic adjustment.

PMID- 16657448
TI  - Auxin transport in Avena: I. Indoleacetic Acid-C distributions and speeds.
AB  - Measurements have been made on the initial stages of the transport of carbon-14
      labeled indoleacetic acid in the coleoptile of Avena sativa L. Concentrations of
      mobile and immobilized indoleacetic acid are related to both distance and time
      during the first 2 hours after application of the indoleacetic acid at several
      concentrations to the top of the decapitated coleoptile.At the lowest
      concentration of indoleacetic acid applied (0.3 mum), the graphs of concentration
      against distance are linear from near the top of the coleoptile to the front of
      the indoleacetic acid stream. The indoleacetic acid possesses a definite front
      moving at constant speed. In the region of the front the graphs are linear even
      with concentrations above 1 mum applied.A large proportion of the mobile
      indoleacetic acid in the coleoptile does not move with the speed of the front of
      the stream. The rate of immobilization of indoleacetic acid by a cell increases
      with time after the arrival of the indoleacetic acid. Each cell must pass on to
      the next nearly all the indoleacetic acid it initially receives.Effects of
      indoleacetic acid application for a short time are investigated, as is the effect
      of triiodobenzoic acid on indoleacetic acid transport. It is deduced that
      diffusion does not play a major part in the normal transport of auxin in the
      coleoptile.

PMID- 16657449
TI  - Investigations of Canavanine Biochemistry in the Jack Bean Plant, Canavalia
      ensiformia (L.) DC: I. Canavanine Utilization in the Developing Plant.
AB  - An ontogenetic study of the canavanine and soluble protein pools in the
      developing jack bean plant, Canavalia ensiformis (L.) DC., was conducted.
      Evidence was presented which clearly established the conversion of canavanine to
      canaline and urea as the principal pathway of canavanine utilization. The
      catabolic reactions of certain bacteria involving the formation of guanidine or
      hydroxyguanidine from canavanine are not operative in the cotyledons of jack
      bean. Evidence was obtained which indicates that a second, minor reaction is
      functioning in canavanine degradation.

PMID- 16657450
TI  - Rapid Changes in Levels of Polyribosomes in Zea mays in Response to Water Stress.
AB  - Sucrose gradient profiles of polyribosomes from the coleoptilar node region of
      seedlings of Zea mays L. were obtained without pelleting and redispersion of the
      particles. Water stress caused a shift of ribosomes from the polymeric to the
      monomeric form, starting about 30 minutes after stress initiation and when the
      water potential of the tissue began to decrease measurably. After about 4 hours
      of stress (a decrease in tissue water potential of about 5 bars), most of the
      higher polymers of ribosomes had shifted to monoribosomes. Release of stress
      caused the ribosomes to revert from monomeric to polymeric form after a lag
      period apparently determined by the extent of prior stress. Use of bentonite and
      isolation of polyribosomes from combined stressed and control tissue gave results
      indicating that the reduced polyribosomal level was not an artifact caused by
      ribonuclease during isolation.Incubating roots in cycloheximide (2 micrograms per
      milliliter) had no effect on the proportion of polyribosomes in control roots,
      but it prevented the loss of polyribosomes caused by stress. Since cycloheximide
      inhibits the release of nascent polypeptide from polyribosomes, it appears
      possible that stress-effected loss in polyribosomes occurs only if polypeptides
      can be terminated and released.

PMID- 16657451
TI  - Effect of Growth Temperature on the Lipid Composition of Cyanidium caldarium: I.
      Class Separation of Lipids.
AB  - Cyanidium caldarium was cultured at 20 and 55 C and harvested during exponential
      growth phase. Comparative lipid studies on each cell type show a decrease by one
      half of the total lipid in cells grown at 55 C over cells grown at 20 C. While
      the distribution of lipid into each of five lipid classes was not influenced by
      high temperature (55 C), the degree of unsaturation was greatly affected. Ratios
      of unsaturated to saturated fatty acids in these cells decreased 3-fold with
      increased temperature in the growth environment. Cells cultured at 20 C contained
      30% of their fatty acids as linolenic while this fatty acid could not be detected
      in cells cultured at 55 C.

PMID- 16657452
TI  - Effect of Growth Temperature on the Lipid Composition of Cyanidium caldarium: II.
      Glycolipid and Phospholipid Components.
AB  - Cyanidium caldarium was grown at 20 and 55 C and harvested during exponential
      growth phase. Lipids were extracted and separated by silicic acid column and thin
      layer chromatography. The major glycolipids were identified as mono- and
      digalactosyl diglyceride and sulfolipid. Major phospholipids were identified as
      phosphatidyl choline and phosphatidyl ethanolamine. The cells grown at 20 C
      contained significantly larger quantities of these glycolipids and phospholipids
      than cells grown at 55 C.Fatty acid analysis showed that in all cases the cells
      grown at 20 C contained more unsaturated fatty acids than the cells grown at 55
      C. Cells grown at 55 C were shown to lack linolenic acid, in contrast to cells
      grown at 20 C, which contained appreciable quantities in certain lipid
      components. For example, monogalactosyl diglyceride had 57% of its fatty acids in
      the form of linolenic acid. Cells grown at 55 C were 10 to 15 C more stable to
      disruption by heating than cells grown at 20 C. The greater thermostability of
      the latter was attributed to a higher degree of saturation of their membrane
      fatty acids.

PMID- 16657453
TI  - The fractionation of transfer ribonucleic Acid from roots of pea seedlings.
AB  - Isoaccepting transfer RNA species for several amino acids were fractionated by
      reverse phase column chromatography. Transfer RNA from dividing cells of pea
      (Pisum sativum) root was compared to that from nondividing cells, and no relative
      quantitative or qualitative differences were noted for the transfer RNA species
      for leucine, lysine, proline, threonine, methionine, serine, and phenylalanine.
      However, certain artifactual differences for serine and phenylalanine were noted.
      Quantitative differences were observed in tyrosyl-transfer RNA's. Ribonuclease
      action on tRNA did not contribute to the tRNA species observed.

PMID- 16657454
TI  - Enzymes of carbohydrate metabolism in the developing endosperm of maize.
AB  - A number of enzymes presumably implicated in starch synthesis were assayed at
      various stages of endosperm development ranging from 8 days to 28 days after
      pollination. Activity for invertase, hexokinase, the glucose phosphate
      isomerases, the phosphoglucomutases, phosphorylase I, uridine diphosphate glucose
      pyrophosphorylase, and the starch granule-bound nucleoside diphosphate glucose
      starch glucosyltransferase was present at the earliest stage of development (8
      days) studied. Activity was detectable for phosphorylase III, the soluble
      adenosine diphosphate glucose-starch glucosyltransferase, adenosine diphosphate
      glucose pyrophosphorylase, and sucrose-uridine diphosphate glucosyltransferase at
      12 days. For phosphorylase II and cytidine diphosphate glucose pyrophosphorylase,
      activity was first detectable at the 14- and 16-day stages, respectively. Rapid
      increases in starch content are observed prior to detectable activity for
      adenosine diphosphate glucose pyrophosphorylase, the soluble adenosine
      diphosphate glucose-starch glucosyltransferase and phosphorylases II and III. For
      all enzymes, except invertase, activity per endosperm rises to a peak at 22 or 28
      days. Greatest activity for invertase is found at 12 days with a steady decline
      thereafter. The pattern of invertase activity in comparison with that of sucrose
      uridine diphosphate glucosyltransferase supports previous suggestions, that the
      latter plays a key role in the conversion of sucrose to starch. In addition to
      phosphorylases I, II, and III, multiple forms of glucosephosphate isomerase and
      phosphoglucomutase were detected.

PMID- 16657455
TI  - Plant epicuticular lipids: alteration by herbicidal carbamates.
AB  - The effect of several carbamates and trichloroacetic acid on the biosynthesis of
      epicuticular lipids from leaves of pea (Pisum sativum) was tested by chemical and
      visual methods. The carbamates tested included S-(2,3-dichloroallyl)
      diisopropylthiocarbamate (diallate), N-(3-chlorophenyl) isopropylcarbamate
      (chloropropham), S-ethyl dipropylthiocarbamate, and 2-chloroallyl
      diethyldithiocarbamate. Diallate reduced epicuticular lipids by 50% when the
      plants were root-treated and by 80% when vapor-treated. These results were
      supported by scanning electron microscopy and carbon replica techniques with
      transmission electron microscopy. The ratio of wax lipid components in the
      diallate-treated plants remained unchanged, with the exception of the primary
      alcohols, which were reduced. Diallate appears to interfere with the biosynthesis
      of a precursor to the elongation-decarboxylation pathway of lipid synthesis. N-(3
      Chlorophenyl)isopropylcarbamate had no significant effect on total amounts of
      extractable epicuticular lipids, nor did it alter the structure of the wax
      formation on the leaves. The scanning electron microscopy micrographs indicated
      that S-ethyl dipropylthiocarbamate significantly reduced wax formation on pea
      leaves. 2-Chloroallyl diethyldithiocarbamate altered the structure of the wax
      formations, but not the total amount of wax (scanning electron microscopy).
      Trichloroacetic acid had little effect on wax deposition compared to diallate or
      S-ethyl dipropylthiocarbamate (scanning electron microscopy). The implication of
      the effect of the carbamates on epicuticular lipids and penetration of subsequent
      topically applied chemicals is discussed.

PMID- 16657456
TI  - Nucleic Acid Metabolism during Greening and Unrolling of Barley Leaf Segments.
AB  - Barley (Hordeum vulgare) leaf segments unroll and green when illuminated.
      Illuminated segments also have an increased capacity for RNA synthesis. Part of
      this increased RNA synthesis may be attributed to an increased RNA polymerase
      activity. In addition, following illumination there is an increased formation of
      polysomes.Analyses of RNA synthesized during illumination showed that the
      radioactive RNA which accumulated was predominantly associated with cytoplasmic
      ribosomal RNAs. It appears that the early phases of greening are achieved without
      chloroplast RNA synthesis. Following extended illumination there was evidence of
      chloroplast ribosomal RNA synthesis; however, this occurred after appreciable
      chlorophyll synthesis. Actinomycin D, which effectively inhibits RNA synthesis
      and leaf unrolling, restricts chlorophyll synthesis only during the later stages
      of illumination. 5-Fluorouracil inhibits the bulk of RNA synthesis but not
      greening, unrolling, or polysome formation. Studies with inhibitors of protein
      synthesis have demonstrated a requirement for protein synthesis concomitant with
      chlorophyll production and leaf unrolling.

PMID- 16657457
TI  - Effect of zinc on translocation of iron in soybean plants.
AB  - Zinc interfered with translocation of iron from roots to above ground parts of
      Glycine max. (L.) Merrill var. Hawkeye. During periods in which zinc impeded iron
      translocation, it also suppressed the production of reductant by roots. Addition
      of iron, as a ferric metal chelate (iron ethylenediaminedihydroxyphenylacetic
      acid), to the growth medium overcame the interference of zinc. In the root
      epidermis, potassium ferricyanide formed a precipitate (Prussian blue) with
      ferrous iron derived from the previously supplied iron
      ethylenediaminedihydroxyphenylacetic acid. The reduction of ferric iron was
      suppressed by zinc.

PMID- 16657458
TI  - Temperature and transpiration resistances of xanthium leaves as affected by air
      temperature, humidity, and wind speed.
AB  - Transpiration and temperatures of single, attached leaves of Xanthium strumarium
      L. were measured in high intensity white light (1.2 calories per square
      centimeter per minute on a surface normal to the radiation), with abundant water
      supply, at wind speeds of 90, 225, and 450 centimeters per second, and during
      exposure to moist and dry air. Partitioning of absorbed radiation between
      transpiration and convection was determined, and transpiration resistances were
      computed.Leaf resistances decreased with increasing temperature (down to a
      minimum of 0.36 seconds per centimeter). Silicone rubber replicas of leaf
      surfaces proved that the decrease was due to increased stomatal apertures. At
      constant air temperature, leaf resistances were higher in dry than in moist air
      with the result that transpiration varied less than would have been predicted on
      the basis of the water-vapor pressure difference between leaf and air.The
      dependence of stomatal conductance on temperature and moisture content of the air
      caused the following effects. At air temperatures below 35 C, average leaf
      temperatures were above air temperature by an amount dependent on wind velocity;
      increasing wind diminished transpiration. At air temperatures above 35 C, leaf
      temperatures were below air temperatures, and increasing wind markedly increased
      transpiration. Leaf temperatures equaled air temperature near 35 C at all wind
      speeds and in moist as well as in dry air.

PMID- 16657459
TI  - Cytokinin Activity in Avocado Seeds during Fruit Development.
AB  - The soybean callus bioassay was used to determine levels of cytokinin activity in
      avocado (Persea americana) seeds.In the embryo, levels are high during the early
      stages of development, but diminish as the fruit grows. The level of cytokinin
      activity in the endosperm is very high throughout the period that this tissue
      exists. The seed coats have very high activity levels while the fruit is young,
      reaching values comparable with those found in the endosperm. The activity level
      falls as the rate of fruit growth slows down and disappears completely by the
      time the seed coats shrivel at approximately the same time the fruit reaches
      "horticultural maturity".

PMID- 16657460
TI  - Cytokinin and inhibitor activities in the avocado fruit mesocarp.
AB  - No cytokinin activity was found in methanolic mesocarp extracts after
      purification with petroleum ether and ethyl acetate. Cytokinin activity did
      appear, however, in aqueous fraction after acid hydrolysis or passage through
      Dowex 50 (H(+)) ion exchange columns. The level of this activity, the fruit
      growth rate, and the cell division rate were found to be positively correlated
      (with each other).An inhibitor to cytokinin activity in soybean callus bioassay
      was found in the petroleum ether fraction; this inhibitor is not abscisic acid.
      The activity of the inhibitor could be considerably reduced by raising the level
      of kinetin in the nutrient medium. The intensity of inhibition was found to be
      positively correlated with reduction in the rate of mesocarp growth.The reduction
      in fruit growth rate may be considered to be due to the diminution of bound
      cytokinin activity and (or) increased activity of an endogenous inhibitor.

PMID- 16657461
TI  - Stomatal dimensions and resistance to diffusion.
AB  - In the past, relations of diffusive resistance to stomatal geometry have
      concerned circular pores or pores that are replaced by equivalent circles of the
      same area. We calculated the resistance for general shapes that include the
      realistic slit. The resistance comprises two terms. The first is an outer
      resistance that depends only on ventilation and leaf geometry and is independent
      of stomata. The second is an inner resistance and is a function of stomatal
      interference and of stomatal geometry only. If interstomatal spacing is at least
      three times stomatal length, interstomatal interference is negligible. The inner
      resistance can then be calculated by adding the resistance of the two ends and
      the throat of each stoma. In the case of an elongated stoma, the part of the
      diffusive resistance per square centimeter determined by stomatal geometry is
      [Formula: see text] where a, b, d, and n are the semilength, semiwidth, depth,
      and density of the stomata, and D is the diffusivity. This is the familiar Brown
      and Escombe result applied to slits.

PMID- 16657462
TI  - Water potential gradients in field tobacco.
AB  - A pressure chamber was used to establish the vertical gradients of leaf water
      potential (Psi(Leaf)) and stem water potential (Psi(Stem)) in field-grown tobacco
      (Nicotiana tabacum L. var. Havanna seed 211) at three different times of day.
      Leaves enclosed in polyethylene bags and aluminum foil the previous afternoon and
      left to equilibrate overnight were used to determine Psi(Stem). The greatest
      difference between Psi(Leaf) and Psi(Stem) occurred in the upper part of the
      plant at 1100 hours Eastern Standard Time and was 5.5 bars. The largest vertical
      gradient in Psi(Stem) occurred at 1300 hours. The soil water potential
      (Psi(Soil)), extrapolated from the potential of leaves on a completely enclosed
      plant, was higher than -1 bar. The vertical gradient in Psi(Stem) and the
      difference between Psi(Leaf) and Psi(Stem) showed the existence of a resistance
      to water movement within the stem (r(stem)) and a further resistance between the
      stem and leaf (r(petiole)). The r(petiole) and root resistance (r(root)) were
      estimated to be 931 and 102 bars seconds per cubic centimeter, respectively. The
      r(stem) was low (94 bars seconds per cubic centimeter) at 1100 hours but
      increased to 689 bars seconds per cubic centimeter at 1300 hours.

PMID- 16657463
TI  - Influence of Water Activity, Temperature, and Their Interaction on Germination of
      Verticillium albo-atrum Conidia.
AB  - Conidia were germinated at three temperatures in media in which available water,
      expressed as water activity, was controlled at three levels. Rate of germination
      in the basal medium (0.9964 water activity) was most rapid at 25 C and was
      inhibited at 15 and 30 C. Lowering the water activity at a particular temperature
      decreased rates of germination. However, at a low water activity (0.9778)
      germination rate was greater at 30 C than at 25 C. Thus, the effect of
      temperature on germination appears to be dependent on the water activity of the
      medium.

PMID- 16657464
TI  - Phytochrome in Cultured Wild Carrot Tissue: II. Dark Transformations.
AB  - Disappearance and transformation of phytochrome in light-treated, dark-grown
      cultured tissue of wild carrot (Daucus carota L.) have been analyzed. Evidence is
      presented for the existence of two populations of far red-absorbing phytochromes:
      one which is subject to reversion, and a second which undergoes loss of
      photoreversibility. Phytochrome levels and transformation characteristics have
      been compared for several strains and developmental stages of cultured wild
      carrot tissue.

PMID- 16657465
TI  - A method for determining the concentration of ethylene in the gas phase of
      vegetative plant tissues.

PMID- 16657466
TI  - Choice of rotation rate for the horizontal clinostat.
AB  - A series of nine rates of rotation of the clinostat were tested to determine
      optimal and acceptable conditions for simulating weightlessness in plants. Young
      seedlings of wheat (Triticum aestivum L.) developed roots and coleoptiles of
      equal lengths and with the same orientation angles over a range of rotation rates
      from 0.25 to 480 minutes per revolution. Rates from 0.25 to 3 minutes per
      revolution provided for maximal epinastic curvatures of leaves and branches of
      Coleus blumei Benth. except for a reduced mean curvature of branches at 0.25
      minute per revolution, due probably to physical disturbances in their growth.
      Smaller epinastic curvatures developed in both leaves and branches rotated at 15
      minutes per revolution or more slowly. Indoleacetic acid-2-(14)C was used for
      measurements of extractable radioactivity in determining the reason for smaller
      curvatures of Coleus branches and tomato (Lycopersicon esculentum Mill.) leaves
      at the rotation rate of 60 minutes per revolution than at 1 minute per
      revolution. The cause was determined to be movement of some auxin from the upper
      into the lower side of a plagiotropic leaf or branch under the transient
      influence of gravity during rotation on the slower clinostat. A rotation period
      of 1 to 3 minutes was found to be acceptable for most plants.

PMID- 16657467
TI  - Prior illumination and the respiration of maize leaves in the dark.
AB  - The course of respiration of attached maize (Zea mays L.) leaves was measured by
      infrared gas analysis of CO(2) efflux in the dark following illumination in
      atmospheres of 300 microliters of CO(2) per liter of air, CO(2)-free air, and
      CO(2)-free N(2) containing 400 microliters of O(2) per liter. CO(2) efflux from
      control leaves started 3 to 4 minutes after darkening, increased to a maximum
      after about 20 minutes, and returned to a steady minimum after 2 to 3 hours.
      Respiration was quantitatively related to prior illumination, independent of net
      CO(2) fixation in the light, and depressed by N(2). Light, but not air, was
      required to produce a substrate for respiration in the subsequent dark period;
      air was required for oxidation of the substrate to CO(2). The stimulation of
      respiration by prior illumination in maize leaves differs in its slower onset and
      greater duration from the postillumination burst of photorespiration.

PMID- 16657468
TI  - Synthesis and Secretion of Hypoxyproline-containing Macromolecules in Carrots:
      III. Metabolic Requirements for Secretion.
AB  - Using pulse-chase experiments with radioactive proline, it is possible to study
      the rapid transfer from the cytoplasm to the cell wall of the hydroxyproline-rich
      protein found in the cell walls of higher plants. The secretion of this protein
      is not obligatorily coupled to protein synthesis. Secretion is completely
      inhibited by uncouplers of oxidative phosphorylation and strongly inhibited by
      the inhibitors of electron transport, cyanide and azide. It is concluded that the
      transfer of proteins from the cytoplasm to the cell wall is an energy-requiring
      step.

PMID- 16657469
TI  - Abnormal Stomatal Behavior and Hormonal Imbalance in flacca, a Wilty Mutant of
      Tomato: I. Root Effect and Kinetin-like Activity.
AB  - The wilty tomato mutant, flacca, and the normal variety, Rheinlands Ruhm, were
      compared for kinetin-like activity in ontogeny. The mutant wilts easily because
      its stomata resist closure. This stomatal resistance decreases with age. The
      occurrence of a root factor which induces stomatal opening was inferred from
      grafting experiments. It was hypothesized that the excessive stomatal openings in
      the mutant may result from excess of kinetin-like activity in the leaf of that
      plant. In addition, it was suggested that the closure of stomata in the aging
      mutant is due to a decrease of kinetin-like activity with age. Kinetin-like
      activity in the leaf was determined by incorporation of labeled leucine. The
      concentration of cytokinins in root exudate and leaf extract was determined by
      the soybean callus assay. Evidence was presented of higher kinetin-like activity
      in the leaves of the mutant and higher cytokinin concentration in its root
      exudate. Cytokinin concentration in the shoot was found to be only slightly
      higher in the mutant than in the normal plants. Kinetin-like activity in the leaf
      and cytokinin concentration of root exudate decreased with age in both mutant and
      normal plants. Kinetin-like activity in the leaves of mutant plants, which
      phenocopy the normal variety as a result of continuous application of abscisic
      acid, was lower than in control mutant plants. The significance of these findings
      per se and in connection with stomatal behavior is discussed.

PMID- 16657470
TI  - Abnormal Stomatal Behavior and Hormonal Imbalance in flacca, a Wilty Mutant of
      Tomato: II. Auxin- and Abscisic Acid-like Activity.
AB  - The wilty tomato mutant, flacca, and the control variety, Rheinlands Ruhm, were
      compared with regard to the endogenous activity and concentration of auxin- and
      abscisic acid-like substances during ontogeny. The mutant wilts fast under water
      deficit because of inability to close its stomata. Symptoms characteristic of
      excessive auxin are evident in the developing mutant. Among these symptoms are
      branch and leaf epinasty, excessive rooting along the stem, and increased apical
      dominance. By using a leucine-incorporation assay, spray of whole plants with 2,4
      dichlorophenoxyacetic acid, and wheat coleoptile bioassay, indications were found
      of an excess of activity and concentration of auxin-like substances in shoots of
      young and mature mutant plants. The wheat coleoptile bioassay also revealed a
      much lower amount of substances with abscisic acid-like activity in the mutant
      compared with the normal plant. In contrast to the appearance during ontogeny of
      morphological symptoms characteristic of auxin excess in the mutant, the absolute
      amount of auxin-like substances and their activity in incorporation of leucine
      decreased with age. A parallel decrease of the concentration and activity of
      auxin-like compounds was also found in the normal plant. The concentration of
      abscisic acid-like substances increased with age in both genotypes. The
      disagreement between the increasing morphological symptoms and the decrease of
      auxin-like activity and concentration is discussed, together with the possibility
      of a causal relationship between auxin-and abscisic acid-like activity and
      stomatal behavior.

PMID- 16657471
TI  - Excretion of Glycolate, Mesotartrate and Isocitrate Lactone by Synchronized
      Cultures of Ankistrodesmus braunii.
AB  - Fixation of (14)CO(2) by synchronized cultures of Ankistrodesmus braunii was
      highest for young growing cells, low for mature cells, and lowest for dividing
      cells. The amount of (14)C excreted during photosynthesis followed the same
      trend. Cells at the end of the growing phase, after 10 hours of a 16-hour light
      phase, excreted nearly 35% of the total (14)C fixed as one product, glycolate.
      Dividing cells from the dark phase, when tested in the light, excreted only 4% as
      much glycolate-(14)C as the young growing cells. Dividing cells also excreted as
      much mesotartrate as glycolate and also some isocitrate lactone and an
      unidentified acid. None of these excreted acids were found inside the cells in
      significant amounts. Methods for isolation and identification of the excreted
      acids are present. With (14)C-labeled algae, it was shown that the excretion of
      glycolate was light-dependent and inhibited by 1,1-dimethyl-3-(p-chlorophenyl)
      urea. The excretion of labeled mesotartrate, isocitrate lactone, and an unknown
      acid, but not glycolate, also occurred in the dark. The excreted mesotartrate was
      predominantly carboxyl-labeled even after long periods of (14)CO(2) fixation.
      Since glycolate is known to be uniformly labeled, glycolate could not be the
      precursor of the carboxyl-labeled mesotartrate. The reason for the specific
      excretion of glycolate, mesotartrate, and isocitrate lactone is not known, but
      the metabolism of all three acids by the algae may be limited and each can form
      dilactides or lactones by dehydration. In this context isocitrate lactone was
      excreted rather than the free acid.

PMID- 16657472
TI  - Glycolate pathway in green algae.
AB  - By three criteria, the glycolate pathway of metabolism is present in unicellular
      green algae. Exogenous glycolate-1-(14)C was assimilated and metabolized to
      glycine-1-(14)C and serine-1-(14)C. During photosynthetic (14)CO(2) fixation the
      distributions of (14)C in glycolate and glycine were similar enough to suggest a
      product-precursor relationship. Five enzymes associated with the glycolate
      pathway were present in algae grown on air. These were P-glycolate phosphatase,
      glycolate dehydrogenase (glycolate:dichloroindophenol oxidoreductase), l
      glutamate:glyoxylate aminotransferase, serine hydroxymethylase, and glycerate
      dehydrogenase. Properties of glycerate dehydrogenase and the aminotransferase
      were similar to those from leaf peroxisomes. The specific activity of glycolate
      dehydrogenase and serine hydroxymethylase in algae was 1/5 to 1/10 that of the
      other enzymes, and both these enzymes appear ratelimiting for the glycolate
      pathway.Labeling patterns for products of the glycolate pathway during (14)CO(2)
      fixation are not the same as those obtained with higher plants. In higher plants
      glycolate, glycine, and serine are uniformly labeled at shortest time periods. In
      algae, serine was predominately carboxyl-labeled, similarly to 3
      phosphoglycerate. This result, plus the lower specific activity of serine
      hydroxymethylase, indicates that the glycine-serine interconversin in algae is
      slower than in plants. Initially (2 to 4 seconds) glycolate and glycine were more
      C-2 labeled. They rapidly became uniformly labeled, with glycine becoming
      uniformly labeled first. In the presence of isonicotinylhydrazide, labeled
      glycolate and glycine accumulated, and only a trace of serine-(14)C was detected.
      Then glycolate and glycine were initially carboxyl-labeled, and glycolate became
      uniformly labeled almost immediately and before glycine. These results suggest
      rapid metabolism of glycolate and glycine, in addition to the glycolate pathway.

PMID- 16657473
TI  - Gibberellins in Relation to Flowering and Stem Elongation in the Long Day Plant
      Silene armeria.
AB  - Two long days induced some flowering and 4 or more long days caused 100%
      flowering in Silene armeria. On long days microscopically detectable flower
      primordia were first seen after 6 days, which is at least 1 day before the start
      of stem elongation. Both gibberellin A(3) and A(7) caused flowering on short
      days, but the results were variable and flowering was never 100%. Three different
      gibberellins were detected in Silene extracts. The pattern of gibberellins
      extracted from plants on short and long days was qualitatively the same, but on
      long days gibberellin content was up to 100% higher than on short days. Only
      small amounts of diffusible gibberellins were obtained from Silene shoot tips
      (including very young leaves) on short days. However, on long days the diffusible
      gibberellins increased by as much as 10-fold after 4 to 6 long days but then
      declined somewhat after 10 long days. The gibberellins extracted from the shoot
      tips at the completion of the diffusion period also increased under long days,
      although the increase was not as large as for the diffusible gibberellins. An
      A(5)-like gibberellin present in extracts was not detected in
      diffusates.Treatment with AMO 1618 (2-isopropyl-4-dimethylamino-5-methylphenyl-1
      piperidine-carboxylate methyl chloride) completely inhibited stem elongation on
      long days but had no effect on flowering. In addition, treatment with AMO 1618
      caused at least an 80% decrease in the level of extractable gibberellin, while
      the diffusible gibberellin was reduced below the limits of detection in the d5
      corn bioassay. When endogenous gibberellin levels were suppressed by pretreatment
      with AMO 1618 on short days, gibberellin A(3) caused more stem elongation in
      plants moved to long days than in plants left on short days. Thus the sensitivity
      of Silene plants to gibberellin with respect to stem growth is affected by
      photoperiod. It is concluded that in Silene endogenous gibberellins are a
      controlling factor for stem elongation but apparently are not required for flower
      formation.

PMID- 16657474
TI  - Some Characteristics of a Lipase Preparation from the Uredospores of Puccinia
      graminis tritici.
AB  - The characteristics of a lipase preparation from the uredospores of Puccinia
      graminis (pers.) f. sp. tritici (Eriks. and Henn.) have been investigated. The
      majority of the lipolytic activity in disrupted uredospores was found to be
      associated with a lipid-containing, particulate fraction which sedimented at
      5000g. With triolein as a substrate, both 1,3- and 1,2-diglycerides were formed.
      Ethylenediaminetetraacetate, p-chloromercuribenzoic acid, and Hg(2+) strongly
      inhibited the activity. A pH optimum of 6.7 was observed. The sensitivity of the
      preparation to higher temperatures was indicated by a complete loss of activity
      when the preparation was preincubated at 25 C or above for 30 minutes. A
      temperature optimum of 15 C for the enzyme is strikingly similar to the
      temperature optimum for germination of the uredospores. The possible relationship
      between the sensitivity of the enzyme and the germination process is discussed.

PMID- 16657475
TI  - Studies on the pyrophosphorylases of wheat.
AB  - Adenosine diphosphoglucose and uridine diphosphoglucose pyrophosphorylase
      activities (class EC 2.7.7.9) were assayed radiochemically in ammonium sulfate
      fractions prepared from mature and germinating wheat grain. Both enzymes showed
      similar pH optima and metal ion requirements but differed markedly in their
      response to activation by d-glycerate 3-phosphate and inhibition by sulfate and
      phosphate.Their stability characteristics also differed greatly. While UDP
      glucose pyrophosphorylase was very stable, ADP-glucose pyrophosphorylase rapidly
      lost activity in dilute solution and upon desalting on columns of Sephadex and
      was only partially stabilized when stored as a suspension in ammonium sulfate.
      Relatively high salt concentrations were required to maintain even short term
      stability. ADP-glucose and UDP-glucose pyrophosphorylases had apparent K(m)
      values for alpha-d-glucose 1-phosphate of 4.4 x 10(-5)m and 10(-3)m,
      respectively. In extracts from dry grain, the number of units of UDP-glucose
      pyrophosphorylase were about 30-fold greater than the number of units of ADP
      glucose pyrophosphorylase. During germination, the activity of UDP-glucose
      pyrophosphorylase increased markedly in both the embryo and the endosperm, while
      ADP-glucose pyrophosphorylase fell slightly over the initial 4 days of
      germination.

PMID- 16657476
TI  - Sex expression in cucumber plants as affected by 2-chloroethylphosphonic Acid,
      ethylene, and growth regulators.
AB  - The effects of 2-chloroethylphosphonic acid (Ethrel), ethylene, and some growth
      retardants on sex expression of cucumber plants (Cucumis sativus L.) were
      investigated, with the use of a monoecious cultivar (Improved Long Green) which
      has a strong tendency toward maleness.Ethrel caused increased femaleness when
      applied at 50 milligrams per liter at the first to the third leaf stage, but when
      applied at the cotyledon stage it was ineffective. The later the time of
      application, the higher the node at which the first female flower appeared. The
      total number of female flowers was about the same regardless of application time.
      A mixture of gibberellins A(4) and A(7) caused maleness, and Ethrel caused
      femaleness. However, when applied in combination at the first leaf stage the
      interaction was not significant. It seems, therefore, that Ethrel and
      gibberellins are not antagonistic but rather have different sites of action,
      although they have opposing effects on sex expression.Ethylene caused femaleness
      but was far less effective than Ethrel. Alar (N-dimethylaminosuccinamic acid),
      CCC((2-chloroethyl)trimethylammonium chloride), Phosphon D(2, 4-dichlorobenzyl
      tributylphosphonium chloride), and abscisic acid did not affect sex expression of
      cucumber.

PMID- 16657477
TI  - Light-induced de Novo Synthesis of Ribulose 1,5-Diphosphate Carboxylase in
      Greening Leaves of Barley.
AB  - An antibody specific for ribulose 1,5-diphosphate carboxylase was used to isolate
      the enzyme from greening barley (Hordeum vulgare L.) leaves. The increase in
      enzymatic activity during greening was due to de novo synthesis of the enzyme.
      Increases in enzymatic activity were accompanied by corresponding increases in
      enzyme protein and by incorporation of radioactive leucine, all of which were
      inhibited by low concentrations of cycloheximide. (14)C-Labeled amino acids were
      incorporated into the enzyme by covalent peptide bonding.

PMID- 16657478
TI  - Effect of Nitrogen Deficiency upon Translocation of C in Sugarcane.
AB  - Withholding nitrogen decreased the percentages of nitrogen and chlorophyll in the
      blades; reduced the total fixation of radioactive carbon dioxide at 15, 37, and
      178 seconds; and changed the relative composition of fixation products.
      Translocation of radioactive photosynthate from the fed part down the attached
      blade and into the stalk was less in the plants deprived of nitrogen than in the
      control plants supplied with nitrogen. Both the percentage of total activity
      translocated and the velocity of transport were decreased by nitrogen deficiency.
      During a translocation period of 90 minutes the minus nitrogen blade retained
      more (14)C-sucrose than the control in the fed part and the blade below the fed
      part, but it sent less (14)C-sucrose to the sheath of the fed leaf. Thus
      translocation decreased with nitrogen deficiency not for lack of sucrose but for
      some other reason. Although withholding nitrogen decreased translocation of
      labeled carbon in and from attached blades, there was no effect upon transport in
      detached blades. The effect of nitrogen deficiency upon translocation may be
      indirect and secondary to the effect upon growth of the plant as a whole.

PMID- 16657479
TI  - The Relationship between the Kinetics of Ribonucleic Acid Accumulation and the
      Morphological Development of the Fern Gametophyte, Dryopteris borreri.
AB  - Fern gametophytes were grown under blue light with and without the addition of 5
      fluorouracil or 8-azaguanine, and under red light. Nucleic acids were extracted
      by either the detergent-chloroform or the detergent-diethylpyrocarbonate method
      and analyzed by polyacrylamide gel electrophoresis. No significant differences in
      the relative distribution of the stable RNA components accompanied the transition
      to biplanar growth. The RNA content per average cell decreased with growth and
      also varied between the cultural conditions, yet it was independent of the
      pattern of morphological development. The falling RNA content per average cell
      resulted from a progressive reduction of the RNA content of the apical cell, as
      determined histochemically. Since filamentous growth occurred by division of this
      apical cell, the rate of cell division was independent of the RNA content of the
      dividing cell.

PMID- 16657480
TI  - Enzymes of starch metabolism in the developing rice grain.
AB  - The levels of starch, soluble sugars, protein, and enzymes involved in starch
      metabolism-alpha-amylase, beta-amylase, phosphorylase, Q-enzyme, R-enzyme, and
      starch synthetase -were assayed in dehulled developing rice grains (Oryzasativa
      L., variety IR8). Phosphorylase, Q-enzyme, and R-enzyme had peak activities 10
      days after flowering, whereas alpha- and beta-amylases had maximal activities 14
      days after flowering. Starch synthetase bound to the starch granule increased in
      activity up to 21 days after flowering. These enzymes (except the starch
      synthetases) were also detected by polyacrylamide gel electrophoresis. Their
      activity in grains at the midmilky stage (8-10 days after flowering) was
      determined in five pairs of lines with low and high amylose content from
      different crosses. The samples had similar levels of amylases, phosphorylase, R
      enzyme, and Q-enzyme. The samples consistently differed in their levels of starch
      synthetase bound to the starch granule, which was proportional to amylose
      content. Granule-bound starch synthetase may be responsible for the integrity of
      amylose in the developing starch granule.

PMID- 16657481
TI  - Effect of absence of developing grain on carbohydrate content and senescence of
      maize leaves.
AB  - In maize (Zea mays L.) grown under normal conditions in Rhodesia, prevention of
      pollination or removal of the ears after flowering caused premature senescence of
      the leaves above the ear, preceded by the appearance of a purplish red color. In
      plants from which the ears had been removed the concentration of sugars and
      starch increased markedly in both upper and lower leaves, the increase being
      greater in the upper leaves.

PMID- 16657482
TI  - Some effects of triton x-100 on pea etioplasts.
AB  - When pea etioplast preparations were treated with Triton X-100, the membranes
      disappeared, the pigments were solubilized, and the organelles appeared to
      disintegrate. Low speed centrifugation (2000g) of the preparations following
      treatment with Triton X-100 resulted in a pellet which contained considerable
      quantities of plastid material. This included RNA polymerase and DNA polymerase
      activity, much of the DNA, about 30% of the RNA, and 50% of the protein of the
      washed plastid. The amount of RNA polymerase and DNA polymerase activity
      associated with the low speed pellet was dependent on the pH during Triton
      treatment. Significant quantities of the RNA polymerase activity of chloroplasts
      from spinach, peas, and tobacco were also recovered in the pellet after Triton
      treatment.

PMID- 16657483
TI  - The effects of simazine and temperature on photosynthesis in rye.
AB  - Temperature during growth had a strong influence on light-saturated rates of
      photosynthesis and respiration in rye (Secale cereale). Carbon dioxide uptake was
      depressed at the low temperatures and reached maximal values higher than 30
      milligrams of carbon dioxide per square decimeter per hour at the intermediate
      temperatures. Respiration rates increased substantially while growth temperature
      decreased. Simazine treatment (0.00, 0.03, 0.08, 0.12 milligrams per liter)
      resulted in no significant stimulatory or inhibitory effects at low temperatures,
      but progressively inhibited growth and photosynthesis at the higher temperatures.
      Respiration rates were not significantly influenced. Thus, the effect of simazine
      is strongly temperature-dependent and is more pronounced on photosynthesis than
      respiration.

PMID- 16657484
TI  - Hydroperoxide isomerase: a new enzyme of lipid metabolism.
AB  - An enzyme has been isolated from flaxseed (Linum usitatissimum) which utilizes
      the product of lipoxidase for its substrate. The enzyme, termed hydroperoxide
      isomerase, converts the conjugated diene hydroperoxide of linoleic acid to the
      corresponding monoenoic ketohydroxy fatty acid. The structure of the latter has
      been determined by ultraviolet, infrared, and nuclear magnetic resonance
      spectroscopy; periodate and permangate oxidation; gas chromatography; and thin
      layer chromatography. Hydroperoxide isomerase activity has also been demonstrated
      in crude extracts from barley (Hordeum vulgare), wheat germ (Triticum aestivum),
      mung beans (Phaseolus aureus), and corn (Zea mays) and from partially purified
      extracts of soybean (Glycine max).The hydroperoxide isomerase enzyme from
      flaxseed has a pH optimum of 7.0. The enzyme was not inhibited by
      nordihydroguairetic acid, p-chloromercuribenzoic acid, or cyanide, but it was
      inhibited by cupric ion. One hundred per cent of the activity was lost by heating
      the enzyme for 1 minute at 68 C. Both linoleic and linolenic acid hydroperoxides
      can serve as substrates for the enzyme. The pH optimum for the hydroperoxide
      isomerase enzyme from barley is 6.2; from wheat germ, 6.1; and from soybean,
      6.1.The identification of the hydroperoxide isomerase enzyme clarifies the role
      of lipoxidase in plant tissue and suggests a participation of lipid in the
      electron transport system.

PMID- 16657485
TI  - Studies on Auxin Protectors: IX. Inactivation of Certain Protectors by Polyphenol
      Oxidase.
AB  - Protector-II (Pr-II) of the Japanese morning glory (Pharbitis nil Choisy) was
      inactivated by exposure to polyphenol oxidase. An unidentified protector in the
      same molecular weight range obtained from sunflower was also inactivated by this
      enzyme. Earlier speculations that protectors might be lipoprotein in nature were
      negated by the fact that neither lipase nor protease inactivated the protectors.
      The protectors were also not inactivated by incubating with alpha-amylase, DNase,
      or RNase. Catechol mimics Pr and is inactivated by polyphenol oxidase. The
      oxidation of catechol to o-quinone is accompanied by a loss of chromophores that
      absorb ultraviolet light and the appearance of a reddish brown color. Similarly,
      when the relatively low molecular weight auxin protectors (Pr-II class) were
      incubated with polyphenol oxidase, their oxidation was also frequently associated
      with the formation of brown color, and oxidation with H(2)O(2) caused a loss of
      ultraviolet-absorbing chromophores. The data indicate that auxin protectors
      contain o-dihydroxyphenolic groups at their active site.That o-dihydroxyphenols
      inhibit indoleacetic acid oxidation has been demonstrated by numerous workers. It
      is suggested that the high molecular weight auxin protectors and the phenolic
      compounds described by other authors comprise part of a metabolic system
      concerned with the regulation of peroxidase-catalyzed redox reactions.

PMID- 16657486
TI  - Relation of glycosidases to bean hypocotyl growth.
AB  - The enzymes beta-glucosidase, alpha-glucosidase, beta-galactosidase, alpha
      galactosidase, and beta-xylosidase were detected in Phaseolus vulgaris L. var.
      Red Kidney bean hypocotyl tissue throughout the first 13 days of development with
      p-nitrophenyl glycosides as substrates. Activities of all enzymes except beta
      glucosidase declined as a function of increasing tissue age. In contrast, beta
      glucosidase activity increased rapidly 3 days after imbibition to a maximal
      activity at 5 days and then subsided to one-third the maximum by day 7. This
      activity peak immediately preceded the logarithmic phase of hypocotyl growth.
      This enzyme is strongly associated with cell walls during extraction, suggesting
      that it is wall-bound in situ. Various polysaccharide substrates were used to
      evaluate the specificity of this enzyme.

PMID- 16657487
TI  - Sicklepod Fatty Acid response to photoperiod.
AB  - Sicklepod (Cassia obtusifolia L.) grew taller and heavier in a 12-hour
      photoperiod than in photoperiods longer or shorter. Total vegetative fatty acid
      content was maximal under 14-hour photoperiods as were unsaturated and branched
      chain fatty acids. Odd-numbered fatty acid content was highest under 16-hour
      photoperiods, and evennumbered fatty acids tended to be more concentrated under
      14-hour photoperiods. Age of plant influenced total vegetative fatty acid
      content.

PMID- 16657488
TI  - Enzyme levels in pea seedlings grown on highly salinized media.
AB  - The levels of 18 enzymes were determined in leaves, stems, and roots of 11-day
      old pea seedlings grown in a liquid medium or in the same medium containing, in
      addition, 5 atmospheres of either NaCl, KCl, Na(2)SO(4), or K(2)SO(4). Though the
      plants grown in saline media were stunted, the specific activities of the enzymes
      were the same in the given tissues of all plants. Also, the electrophoretic
      pattern of isozymes of malate dehydrogenase was not altered by growth of the
      plants in a saline medium. However, the isozyme pattern of peroxidase from roots
      of salt-grown plants was altered in that two of the five detectable isozymes
      migrated a little more slowly than those in extracts from nonsaline plant
      tissues.

PMID- 16657489
TI  - Glyoxysomes in megagamethophyte of germinating ponderosa pine seeds.
AB  - Decoated ponderosa pine (Pinus ponderosa Laws) seeds contained 40% lipids, which
      were mainly stored in megagametophytic tissue and were utilized or converted to
      sugars via the glyoxylate cycle during germination. Mitochondria and glyoxysomes
      were isolated from the tissue by sucrose density gradient centrifugation at
      different stages of germination. It was found that isocitrate lyase, malate
      synthase, and catalase were mainly bound in glyoxysomes. Aconitase and fumarase
      were chiefly localized in mitochondria, whereas citrate synthase was common for
      both. Both organelles increased in quantity and specific activity of their
      respective marker enzymes with the advancement of germination. When the
      megagametophyte was exhausted at the end of germination, the quantity of these
      organelles and the activity of their marker enzymes decreased abruptly. At the
      stage of highest lipolysis, the isolated mitochondria and glyoxysomes were able
      to synthesize protein from labeled amino acids. Both organellar fractions
      contained RNA and DNA. Some degree of autonomy in glyoxysomes is indicated.

PMID- 16657490
TI  - Light-dependent Influx and Efflux of Potassium of Guard Cells during Stomatal
      Opening and Closing.
AB  - Stomata in epidermal strips of Vicia faba opened in light and closed in darkness
      when floated on dilute K(+) solutions. Opening and closing, respectively,
      paralleled the fluxes of labeled K(+) into and out of the strips. The gain and
      loss of K(+) by the strips were shown by colbaltinitrite stain to be centered at
      guard cells. Intact epidermal cells, however, appeared to take up K(+),
      complicating interpretation of the data.The specific requirement of K(+) for
      stomatal opening in light appeared to be related to the specific uptake of K(+).
      There was little or no light stimulation of opening in strips on Na(+), nor was
      there stimulation of Na(+) uptake. The marked light stimulation of opening on
      K(+) was generally matched by stimulation of K(+) uptake.Anaerobiosis markedly
      reduced opening in leaf discs but not in strips. Under anaerobic conditions,
      opening in strips was not appreciably affected by 3(3,4-dichlorophenyl)-1,1
      dimethylurea (diuron) but was completely inhibited by carbonyl cyanide m
      chlorophenylhydrazone plus diuron. Inhibition of opening was generally correlated
      with inhibition of K(+) uptake by the strips. Also stomata in strips opened well
      under far red light (>700 nanometers). These data suggest that photosystem I and
      cyclic electron flow can supply the necessary energy for K(+) uptake and stomatal
      opening.

PMID- 16657491
TI  - Studies on the kinetics of photosynthetic products synthesized by different
      preparations of intact spinach chloroplasts.

PMID- 16657492
TI  - Relation of the Light-dependent Potassium Uptake by Pea Leaf Fragments to the pK
      of the Accompanying Organic Acid.

PMID- 16657493
TI  - Abscisic Acid-induced Changes in Nucleotide Composition of Rapidly Labeled
      Ribonucleic Acid Species of Lentil Root: Reversal by Kinetin.

PMID- 16657494
TI  - Cytokinin activity in rose petals and its relation to senescence.
AB  - Cytokinin activity in young rose petals was higher than in old ones. The content
      of endogenous cytokinins in petals of a short-lived variety (Golden Wave) was
      lower than in a long-lived variety (Lovita). Application of the cytokinin, N(6)
      benzyladenine, increased longevity of the short-lived variety. This strengthens
      the view that cytokinins participate in the endogenous regulation of senescence
      in rose petals.

PMID- 16657495
TI  - Fat Metabolism in Higher Plants: XL. Synthesis of Fatty Acids in the Initial
      Stage of Seed Germination.
AB  - To understand more fully organelle membrane assemblage, the synthesis of the
      first fatty acids by the germinating pea, Pisum sativum, was studied by the
      incorporation of either tritiated water or acetate-1-(14)C into lipids by the
      intact, initially dry seed. After a lag phase, labeling proceeded linearly. This
      lag phase ended when uptake of water had increased the seed weight to 185% of its
      original weight. The first fatty acids synthesized were palmitic and stearic
      followed shortly after by long chain saturated fatty acids (C(20)-C(26)). The
      synthesis of very long chain acids was consistently characteristic of several
      other seeds in early stages of germination. The majority of the radioactive acids
      were present in phospholipids and were localized in particulate fractions. The
      acyl components of phosphatidyl glycerol were highly labeled. The very long chain
      acids were found predominantly in the waxes. Pulse labeling indicated little
      turnover of the labeled fatty acids. Evidence is presented indicating that the
      enzymes for fatty acid synthesis are already present in the dry seed and
      participate in the synthesis of fatty acids once a critical water content of the
      seed is achieved.

PMID- 16657496
TI  - Effects of light and growth regulators on leaf unrolling in barley.
AB  - The influence of light, gibberellic acid, and abscisic acid on unrolling of
      etiolated barley leaf segments was investigated. Gibberellic acid stimulated
      unrolling of both illuminated and nonilluminated leaf segments. In contrast,
      abscisic acid prevented light-stimulated unrolling and abolished the slight
      unrolling of segments maintained in the dark.Analysis of the time course of
      photoinduced unrolling showed a lag period of 6 hours before the onset of rapid
      leaf unrolling. The application of gibberellic acid to illuminated segments
      shortened this lag phase. Also, incubating the segments in buffer in darkness
      prior to illumination eliminated the lag period. Inhibitors of RNA and protein
      synthesis prevented light- and gibberellic acid induced unrolling, indicating a
      requirement for macromolecular synthesis. The possibilities that the lag period
      of unrolling following illumination represents the time required for the removal
      of endogeneous inhibitor or the synthesis of essential macromolecules are
      discussed.

PMID- 16657497
TI  - Measuring Osmotic Pressure of Sap within Live Cells by Means of a Visual Melting
      Point Apparatus.
AB  - A freezing slide apparatus is described for visual observation of freezing water
      and melting ice within plant cells. The slide consists of an ordinary microscope
      slide glued into a Plexiglass jacket, through which cold 90% ethyl alcohol is
      pumped at varying rates for temperature control. Temperature is recorded by means
      of an iron-constantan thermocouple wire (25-micron diameter) connected to a
      recording potentiometer. Tissue strips were quick frozen (at a cooling rate of 33
      C per (1/2) minute) and then warmed very slowly (at a rate of 2 C per minute) for
      observation of melting points. This apparatus has been used to determine osmotic
      pressures of cell sap of guard and adjoining epidermal cells of Chrysanthemum
      morifolium and Pelargonium hortorum. An accuracy of +/- 1.2 atmospheres is
      possible. Wide variations among osmotic pressures of both guard and epidermal
      cells were found at any one stomatal aperture in both species.

PMID- 16657498
TI  - Protein and Ribonucleic Acid Synthesis during Germination of Uredospores.
AB  - Existing evidence suggests that there is no net synthesis of protein during
      germination of spores of some obligate parasites. The problem was reinvestigated
      with enzymatic hydrolysis, rather than acid hydrolysis or solubility properties,
      to estimate changes in protein and RNA. Procedures are detailed for the use of
      uniformly labeled (14)C-uredospores for the isolation and quantitative assay of
      amino acids and nucleosides resulting from hydrolysis.During early stages of
      germination in the absence of exogenous substrates, nucleosides derived
      enzymatically from RNA do not increase nor does the base composition vary. The
      bases of the free nucleotide pool, although varying in concentration from the RNA
      bases, also remain constant during this time. After 16 or 24 hours, bases from
      both sources decrease appreciably, and the decline is correlated with leakages to
      the external medium.In contrast to previous reports, amino acids released by
      proteases increased 20 to 25% during the first 3 to 5 hours of germination but
      decreased after 16 to 24 hours. The results suggest that spores of obligate
      parasites have a functional protein synthetic system which is involved in
      germination. Previous negative findings may have resulted from a lack of
      specificity in the analytic procedures employed, coupled with the possibility
      that protein or amino acid is associated with the walls of spores and the walls
      of germ tubes.

PMID- 16657499
TI  - Modification of Pattern of Photosynthate Movement within and between Shoots of
      Vitis vinifera L.
AB  - During the prebloom and bloom stages, no movement of labeled photosynthates
      occurred from a shoot of Vitis vinifera L. fed with (14)CO(2), to an adjacent
      shoot on the same spur. Movement of labeled assimilates into the unfed shoot was
      induced when this shoot was sprayed with 2.89 x 10(-3)m gibberellic acid during
      the prebloom stage. During the bloom stage darkening or defoliation of the unfed
      shoot resulted in the import of labeled photosynthates from the adjacent fed
      shoot. Similarly, movement of (14)C into an untreated shoot was induced by
      removing the terminal 7.5 centimeters and deblossoming the fed shoot. During the
      berry set stage, translocation of labeled photosynthates from a newly exporting
      leaf was upwards to the shoot tip, but the direction of movement was reversed by
      removal of the shoot tip or by darkening or removal of the leaves below the fed
      leaf. Translocation of photosynthates was predominantly basipetal from a fed leaf
      near the base of the shoot during the berry set stage, but upward movement was
      induced by darkening or defoliation of the upper part of the shoot.

PMID- 16657500
TI  - Inhibitors from Carob (Ceratonia siliqua L.): II. Effect on Growth Induced by
      Indoleacetic Acid or Gibberellins A(1), A(4), A(5), and A(7).
AB  - Two inhibitory fractions (B(1) and C) from extracts of immature fruit of carob
      were tested for their ability to inhibit the action of indoleacetic acid (IAA) in
      three bioassays. There was no reduction of IAA-induced reactions in the Avena
      curvature test, abscission of debladed coleus petioles, or growth of cucumber
      hypocotyls. The highest ratio of inhibitor to IAA was 10,000 times greater than
      the ratio necessary to inhibit by 50% the growth caused by an equivalent amount
      of gibberellin A(3) in pea seedlings. At the highest concentration used, fraction
      C alone caused curvature of Avena coleoptiles. The inhibitory fractions appeared
      to enhance the effect of IAA in the cucumber test.Concentrated whole extract and
      fractions B(1) and C were tested for reduction of growth caused by gibberellins
      A(1), A(4), A(5), A(7), and a neutral gibberellin-like substance from beans in
      the dwarf-5 maize bioassay. Each gibberellin was inhibited and required the same
      amount of inhibitor for a 50% reduction of the induced growth. The inhibiting
      effect could be completely overcome by increasing the amount of gibberellin while
      maintaining the same concentration of inhibitor. Fractions B(1) and C were also
      tested with gibberellins A(2) and A(4) in the cucumber hypocotyl test. Both
      inhibitory fractions reduced growth but were more effective against gibberellin
      A(3) than gibberellin A(4) in the assay. The ability to reduce gibberellin
      induced growth and not reduce IAA-induced growth indicates that the inhibitors
      from carob have a greater specificity of action than that previously reported for
      any inhibitor.

PMID- 16657501
TI  - Plant gas exchange at high wind speeds.
AB  - High altitude Rhododendron ferrugineum L. and Pinus cembra L. seedlings were
      exposed to winds at 15 meters per second for 24-hour periods. Wind-sensitive
      stomata of Rhododendron seedlings immediately initiated a closing response which
      resulted in decreased photosynthesis and an even greater reduction in
      transpiration. Stomatal aperture and transpiration rates of P. cembra were only
      slightly reduced by high speed winds. However, photosynthesis was substantially
      reduced because of changes in needle display to available irradiation.

PMID- 16657502
TI  - Effects of organic acids on ion uptake and retention in barley roots.
AB  - Effects of several organic acids on ion uptake and retention and on respiration
      in barley roots having low and high KCl contents were assayed by measurements of
      K(+), Na(+), Ca(2+), Cl(-), and oxygen uptake. Organic acids with high pK(a)
      values increase the permeability of roots to ions and decrease respiration when
      present in sufficient concentrations at pH 5 but have no inhibitory effects at pH
      7. Absence of respiratory inhibition in short times and at lower organic acid
      concentrations, under conditions that immediately produce a permeability
      increase, indicate that the permeability change is not a result of respiratory
      inhibition. Effects of formate, acetate, propionate, and glutarate are attributed
      to entry of undissociated acid molecules into the effective membranes. Lack of a
      permeability increase with succinate, which has lower distribution coefficients
      to lipid solvents than do the aliphatic acids, can be explained by failure of
      sufficient amounts of the hydrophilic succinic acid molecules to penetrate the
      membranes involved. These experiments suggest that undissociated acid in root
      membranes can increase permeability of the roots.

PMID- 16657503
TI  - Porphyrin Biosynthesis in Cell-free Homogenates from Higher Plants.
AB  - The porphyrin and phorbin biosynthetic activity of etiolated cucumber (Cucumis
      sativus, L.) cotyledons was compared to that of cotyledonary homogenates.
      Etiolated cotyledons incubated with delta-aminolevulinic acid accumulate
      protoporphyrin, coproporphyrin, small amounts of Mg protoporphyrin monoester, and
      trace amounts of uroporphyrin. They also incorporate 4-(14)C-delta-aminolevulinic
      acid into free porphyrins, protochlorophyllide, protochlorophyllide phytyl ester,
      and Mg protoporphyrin monoester. Homogenates incubated with delta-aminolevulinic
      acid likewise accumulate coproporphyrin, uroporphyrin, Mg coproporphyrin, and
      trace amounts of protoporphyrin. They also incorporate 4-(14)C-delta
      aminolevulinic acid into Mg protoporphyrin monoester, Mg coproporphyrin, and free
      porphyrins. However, the capacity to synthesize protochlorophyllide and
      protochlorophyllide phytyl ester is lost and the endogenous protochlorophylls
      gradually disappear. Mg protoporphyrin monoester represents the terminal
      biosynthetic step in this cell-free system.

PMID- 16657504
TI  - Mechanics of the compression wood response: I. Preliminary analyses.
AB  - Righting of two tilted white pine (Pinus strobus L.) stem leaders by compression
      wood formation was followed for 16 weeks. The natural curves and three deflection
      curves under added end loads were determined from weekly field photographs. Data
      for self-loading and cross sectional diameters were interpolated from original
      estimated and final measurements. A mechanical-mathematical model was developed
      to predict curves under zero gravity for each stem each week. The model estimated
      stiffness of the leaders independently for each week, and the stiffnesses were
      consistent throughout the experiment. A second model was developed to simulate
      the deflection curves assumed when the zero gravity curves were subjected to
      different end loads. These predicted curves were nearly identical to the observed
      curves from the photographs, thus verifying the assumptions in the first model.
      Data from this study will be used to investigate the mechanical aspects of
      compression wood induction and action as the stem is bent upward toward the
      vertical.

PMID- 16657505
TI  - Transient heat and mass transfer from a leaf undergoing stomatal closure in a low
      pressure environment.
AB  - Stomatal control of water loss was studied in a low pressure environment by using
      detached leaves of Crassula argentea Thunb., Peperomia obtusifolia (L.) A.
      Dietr., and Setcreasea pallida Rose cv. ;Purple Heart.' The transient behavior of
      temperature and rate of mass loss were determined. A model based on free molecule
      gas flow was developed and used to predict mass loss to within the same order of
      magnitude of experimentally obtained results. By utilizing this model, the
      transient behavior of stomatal aperture was determined. The "nonphysiological"
      experimental conditions do not inhibit the closing process; therefore, this new
      experimental technique is a valid method of studying stomatal closure.

PMID- 16657506
TI  - The relation of carbon dioxide compensation and chlorenchymatous vascular bundle
      sheaths in leaves of dicots.
AB  - Low CO(2) compensation points have been found to be associated with several
      unusual characteristics related to photosynthesis. One such characteristic is a
      prominent, chlorenchymatous vascular bundle sheath in the leaves. It has been
      suggested that the presence of this sheath in dicotyledons can serve as a means
      of detecting low CO(2)-compensating species. We collected 88 dicotyledon species
      from 22 families reported to have chlorenchymatous sheaths. Of the 88, only
      three, Tribulus terrestris, L., Boerhaavia paniculata, L. C. Rich, and Trianthema
      portulacastrum L., had low CO(2) compensation points. Cross sections of the
      leaves of the other species revealed that they did have chlorenchymatous vascular
      bundle sheaths. However, these sheath cells contained chloroplasts which were not
      specialized for starch formation as were the bundle sheath chloroplasts of the
      low CO(2)-compensating species.

PMID- 16657507
TI  - The photosynthetic response to a shift in the chlorophyll a to chlorophyll B
      ratio of chlorella.
AB  - The chlorophyll a:b ratio was shifted in Chlorella vannielii by varying the
      illuminance under which the cells were cultured-the ratio increased from 2.9,
      3.0, 4.0, and 4.8 to 6.2, respectively, at 100, 300, 900, 2,700 and 6,000 foot
      candles. The 6,000-foot candle cells retained an optimal growth rate at the
      chlorophyll a:b ratio of 6.2 which was the upper limit of normal growth.
      Comparisons were made between the 300-and 6,000-foot candle cultures to determine
      the significance to the photosynthetic mechanism of a shift in the chlorophyll
      a:b ratio.The high light cells (6,000 foot candles) contained only one-tenth the
      total amount of chlorophyll of the low light cells (300 foot candles) based on
      dry weight. The total chlorophyll per cell of the high light cells was one-fifth
      of that in the low light cells. Electron micrographs indicated differences in
      chloroplast structure. An average of five or six thylakoids composed a granum
      like region of the low light chloroplasts, whereas only a pair of thylakoids at
      most was found in the high light chloroplasts. The high light chloroplasts had
      more starch. On a dry weight basis, the high light cells had a respiration rate 3
      times that of the low light cells. Based on chlorophyll, the respiration rate of
      the high light cells was 26 times greater. Based on dry weight, the oxygen
      evolution for both cultures was essentially the same at 6,000 foot candles;
      however, at 300 foot candles the rate for the low light cells was about 5 times
      faster than that of the high light cells. With chlorophyll as the index, the
      rates of the high light cells were higher than those of the low light cells-7
      times faster at 6,000 and 2 times faster at 300 foot candles. At 10,000 foot
      candles, the low light-grown cells underwent photooxidation, whereas the high
      light grown cells photosynthesized at a rate slightly higher than at 6,000 foot
      candles.Action spectra of system II (oxygen evolution) from a modulated
      polarograph indicated photochemical participation of chlorophyll b in the high
      light deficient cells, although the participation was much less than in the low
      light cells. Enhancement was 1.11 for the low light cells, and 1.05 for the high
      light cells.In order to account for the energy balance in the two cultures it was
      concluded that perhaps oxidative phosphorylation supplemented a reduced
      photophosphorylation in the high light cells. Experiments with peroxyacetyl
      nitrate support the view that cyclic photophosphorylation is less in the
      chlorophyll b-deficient cells. Chlorophyll b served also to broaden absorption
      for the photosynthetic unit-a detrimental role when cells are illuminated above
      saturation.

PMID- 16657508
TI  - Characterization of a Photosynthetic Mutant Strain of Chlamydomonas reinhardi
      Deficient in Phosphoribulokinase Activity.
AB  - A mutant strain of the unicellular green alga, Chlamydomonas reinhardi, is unable
      to fix carbon dioxide by photosynthesis because it is deficient in
      phosphoribulokinase activity. The absence of light-dependent carbon dioxide
      fixation in cells of the mutant strain supports the operation of the Calvin
      Benson scheme of photosynthetic carbon dioxide fixation in this organism. No
      deficiency other than low phosphoribulokinase activity was found which would
      account for the inability of cells of the mutant strain to fix carbon dioxide by
      photosynthesis. Activities comparable to those in the wild-type strain were found
      for eight other enzymes of the Calvin cycle and two enzymes associated with the
      C(4) dicarboxylic acid pathway. The normal rates of nicotinamide adenine
      dinucleotide phosphate photoreduction and of photosynthetic phosphorylation
      observed in chloroplast fragments prepared from cells of the mutant strain
      indicated that the photosynthetic electron transport chain in the mutant is
      intact.

PMID- 16657509
TI  - Ribonucleic Acid Synthesis by Cucumber Chromatin: Developmental and Hormone
      induced Changes.
AB  - When intact etiolated 2-day cucumber (Cucumis sativus) embryos were treated with
      indoleacetic acid (IAA), gibberellin A(7) (GA(7)), or kinetin, chromatin derived
      from the embryonic axes exhibited an increased capacity to support RNA synthesis
      in either the presence or the absence of bacterial RNA polymerase. An IAA effect
      on cucumber RNA polymerase activity was evident after 4 hours of hormone
      treatment; the IAA effect on DNA template activity (bacterial RNA polymerase
      added) occurred after longer treatments (12 hours). GA(7) also promoted template
      activity, but again only after a prior stimulation of endogenous chromatin
      activity. After 12 hours of kinetin treatment, both endogenous chromatin and DNA
      template activities were substantially above control values, but longer kinetin
      treatments caused these activities to decline in magnitude. When chromatin was
      prepared from hypocotyl segments that were floated on a GA(7) solution, a GA
      induced increase in endogenous chromatin activity occurred, but only if cotyledon
      tissue was left attached to the segments during the period of hormone
      treatment.Age of the seedling tissue had a profound influence on the chromatin
      characteristics. With progression of development from the 2-day to the 4-day
      stage, the endogenous chromatin activity declined while the DNA template activity
      increased.

PMID- 16657510
TI  - alpha-Amylase Isozymes in Gibberellic Acid-treated Barley Half-seeds.
AB  - The presence of multiple forms of alpha-amylase in gibberellic acid-treated
      embryoless barley half-seeds was demonstrated by separation on diethylaminoethyl
      Sephadex and isoelectric focusing polyacrylamide gel disc electrophoresis. Two
      major alpha-amylase fractions (A and B), each consisting of two to three isozyme
      components, were purified. alpha-Amylase fractions A and B were distinguishable
      in their reaction patterns. The optimal pH of fraction A alpha-amylase was found
      to reside in the acidic side (pH 5.0), as was determined by analyzing the
      reducing sugars formed as well as the paper chromatographic detection of reaction
      products. At neutral pH, 6.9, fraction A exhibited weak amylolytic activity in
      forming maltose. The alpha-amylase activity in fraction A was markedly stimulated
      by heat treatment (70 C/15 minutes). Fraction B, constituting a major part of
      amylases in the endosperm extract, was also found to be composed of alpha
      amylase, as evidenced by the loss of enzyme activity upon allowing fractions A
      and B to stand at pH 3.3 for a prolonged period. The possible physiological
      function of the two different types of alpha-amylase in the carbohydrate
      breakdown of barley seeds is discussed.

PMID- 16657511
TI  - Dark Reversion of Phytochrome in Sinapis alba L.
AB  - Phytochrome in Sinapis alba L. (white mustard) seedlings undergoes both decay and
      reversion after an exposure to red light. This is typical of other crucifers and
      of dicotyledons in general. In the presence of sodium azide, decay is inhibited,
      and reversion continues at about the same rate as in buffer alone. The reversion
      has been demonstrated both in cotyledon plus hypocotyl hook and in hypocotyl hook
      samples alone and is of the same order of magnitude in both. Contrary conclusions
      in the literature that there is no reversion in Sinapis are based on indirect
      measurements and are unjustified.

PMID- 16657512
TI  - The development of glyoxysomes in maize scutellum: changes in morphology and
      enzyme compartmentation.
AB  - Changes in the ultrastructural aspect of the glyoxysome fraction obtained from
      maize scutella by density gradient centrifugation were followed during the first
      6 days of germination. During the first 2 days the fraction consists of very
      electron-dense bodies about 0.3 to 0.5 micron in size while at the 4th day it is
      formed by larger and less dense membrane-bound particles. Some intermediate form
      between the two types of organelles can be seen at the 3rd day. Between the 4th
      and the 6th days of germination the glyoxysomes are destroyed, and their enzymes
      are released into the cytosol. At the peak of their development (4th day) the
      glyoxysomes contain 75 to 80% of the total isocitratase and 65% of the total
      malate synthetase of the scutellum. These values drop to very low levels during
      the next 2 days. Catalase bound to glyoxysomes amounts to 30 to 35% of the total
      activity present in the scutellum at the 1st day of germination: this value
      decreases steadily during the following days.

PMID- 16657513
TI  - Metabolic Changes in Partially Dormant Wheat Seeds during Storage.
AB  - Changes in germination, seedling growth, respiration, response to applied
      gibberellic acid, and glucose-U-(14)C utilization were investigated in partially
      dormant wheat (Triticum aestivum L., Pa 151 x 107) seeds which were stored under
      various conditions for periods up to 1 year. Only seeds stored at -20 C and 12.4%
      moisture maintained partial dormancy, which was overcome by germinating in 10(
      3)m gibberellic acid. Germination and seedling growth of seeds stored at 25 C and
      15.1% moisture declined within 12 weeks and the percentage of seeds infected with
      storage fungi increased. Gibberellic acid produced faster growing seedlings,
      particularly from those seeds with partial dormancy, but did not overcome growth
      reduction which was caused by deterioration. Seeds kept under laboratory
      conditions (B), 25 C and 12.1% moisture (C), and 25 C and 15.1% moisture (D) for
      12 weeks utilized 35, 55, and 80% less glucose, respectively, than those stored
      at -20 C and 12.4% moisture (A). Seeds stored under B and C consistently had
      higher germination, growth, and respiratory rates than seeds from A and D. The
      respiratory rate declined as deterioration advanced under D. Respiratory
      quotients ranged from 1.0 for seeds stored under A to 1.6 for seeds stored under
      D.

PMID- 16657514
TI  - Response of Spirodela oligorrhiza to Phosphorus Deficiency.
AB  - The duckweed Spirodela oligorrhiza, growing in sterile defined nutrient media,
      was used to study some responses of plants to phosphorus deficiency. On a
      phosphate-deficient medium, growth of Spirodela soon slowed and eventually
      ceased. Older leaves became chlorotic, but newly formed leaves were dark green
      and contained much anthocyanin. The photosynthesis rate fell gradually, roots
      elongated, and chloroplasts became filled with starch.NITROGEN METABOLISM WAS NOT
      MARKEDLY AFFECTED: the total protein content changed only slightly, and, although
      levels of glutamine and asparagine increased, the concentrations of the other
      amino acids remained constant. The effects of phosphorus deficiency on Spirodela
      are discussed in relation to those found in other higher plants.

PMID- 16657515
TI  - Retardation of bean leaf senescence by benzyladenine and its influence on
      phosphate metabolism.
AB  - The levels of glucose, sugar phosphates, and adenosine phosphates were determined
      in primary leaves of intact bean plants during normal senescence and compared to
      leaves in which senescence was delayed by application of benzyladenine (BA). In
      both cases there was a rise with time in the levels of glucose 1-phosphate,
      glucose 6-phosphate, and fructose 6-phosphate, and a decline in 2-phosphoglyceric
      acid, inorganic phosphate, and the adenosine phosphates (AMP, ADP, ATP). The
      levels of fructose 1,6-diphosphate remained fairly constant. Although the levels
      of hexose phosphates, adenosine phosphates, and inorganic phosphate were lower in
      the BA-treated leaves, the incorporation of (32)P into these compounds by 3- and
      6-week-old plants was higher than in the controls. These results suggest that the
      retardation of leaf senescence by BA in intact bean plants is associated with
      increased utilization of metabolites, indicating a more rapid turnover of the
      adenosine phosphates. It is concluded that this effect is brought about by a
      regulatory coordination of metabolic processes in relation to energy production
      and utilization.

PMID- 16657516
TI  - The Respiratory Chain of Plant Mitochondria: VII. Kinetics of Flavoprotein
      Oxidation in Skunk Cabbage Mitochondria.
AB  - The oxidation kinetics of the two high potential flavo-proteins, one (Fp(hf))
      fluorescent and the other (Fp(ha)) nonfluorescent, in mitochondria from skunk
      cabbage (Symplocarpus foetidus) spadices have been measured by combined
      spectrophotometry and fluorimetry. In the absence of respiratory inhibitors, both
      flavoproteins are oxidized at nearly the same rate with half-times between 120
      and 160 milliseconds at 24 C. When slight differences in rate are observed, it is
      Fp(ha) which consistently has the shorter half-time. The presence of 0.3
      millimolar KCN has no perceptible effect on the oxidation rate of either
      component. Antimycin A (2 nanomoles per milligram of protein) increases the
      oxidation half-time of Fp(ha) about 3-fold, but it has no effect on the oxidation
      half-time of Fp(hf). In contrast to these two inhibitors, m-chlorobenzhydroxamic
      acid-an inhibitor specific to the cyanide insensitive, alternate oxidase pathway
      in these mitochondria-increases the oxidation half-time of Fp(hf) 10-fold to
      about 2 seconds, while increasing that of Fp(ha) only some 20%. This result
      implies that the flavoprotein Fp(hf) mediates electron transport to the alternate
      oxidase from the region of the mitochondrial respiratory chain encompassing
      Fp(ha), ubiquinone, and the cytochromes b. The oxidation rate of cytochrome
      b(557) is unaffected by either m-chlorobenzhydroxamic acid or cyanide but is
      strongly inhibited by antimycin A. This result implies that cytochrome b(557)
      plays no direct role in the respiratory pathway to the alternate oxidase and is
      different from cytochrome b(7) found in mitochondria from the spadices of Arum
      maculatum.

PMID- 16657517
TI  - The Respiratory Chain of Plant Mitochondria: VIII. Reduction Kinetics of the
      Respiratory Chain Carriers of Mung Bean Mitochondria with Reduced Nicotinamide
      Adenine Dinucleotide.
AB  - Addition of 90 micromolar reduced nicotinamide adenine dinucleotide (NADH) in the
      presence of cyanide to a suspension of aerobic mung bean (Phaseolus aureus)
      mitochondria depleted with ADP and uncoupler gives a cycle of reduction of
      electron transport carriers followed by reoxidation, as NADH is oxidized to
      NAD(+) through the cyanide-insensitive, alternate oxidase by excess oxygen in the
      reaction medium. Under these conditions, cytochrome b(553) and the
      nonfluorescent, high potential flavoprotein Fp(ha) of the plant respiratory chain
      become completely reduced with half-times of 2.5 to 2.8 seconds for both
      components. Reoxidation of flavoprotein Fp(ha) on exhaustion of NADH is more
      rapid than that of cytochrome b(553). There is a lag of 1.5 seconds after NADH
      addition before any reduction of ubiquinone can be observed, whereas there is no
      lag perceptible in the reduction of flavoprotein Fp(ha) and cytochrome b(553).
      The half-time for ubiquinone reduction is 4.5 seconds, and the extent of
      reduction is 90% or greater. About 30% of cytochrome b(557) is reduced under
      these conditions with a half-time of 10 seconds; both cytochrome b(562) and the
      fluorescent, high potential flavoprotein Fp(hf) show little, if any, reduction.
      The two cytochromes c in these mitochondria, c(547) and c(549), are reduced in
      synchrony with a half-time of 0.8 second. These two components are already 60%
      reduced in the presence of cyanide but absence of substrate, and they become
      completely reduced on addition of NADH. These results indicated that reducing
      equivalents enter the respiratory chain from exogenous NADH at flavoprotein
      Fp(ha) and are rapidly transported through cytochrome b(553) to the cytochromes
      c; once the latter are completely reduced, reduction of ubiquinone begins.
      Ubiquinone appears to act as a storage pool for reducing equivalents entering the
      respiratory chain on the substrate side of coupling site 2. It is suggested that
      flavoprotein Fp(ha) and cytochrome b(553) together may act as the branching point
      in the plant respiratory chain from which forward electron transport can take
      place to oxygen through the cytochrome chain via cytochrome oxidase, or to oxygen
      through the alternate, cyanide-insensitive oxidase via the fluorescent, high
      potential flavoprotein Fp(hf).

PMID- 16657518
TI  - Physiological Studies on Pea Tendrils: VII. Evaluation of a Technique for the
      Asymmetrical Application of Ethylene.
AB  - A technique has been devised for the asymmetrical application of ethylene to
      specific surfaces of plant tissue. 2-Chloroethylphosphonic acid (CEPA) was
      dissolved in a phosphate buffer (pH 6.5) containing Tween-20 or dimethylsulfoxide
      as adjuvant. Ethylene evolution from tendrils of Pisum sativum cv. Alaska was
      greater during coiling than when they were at rest; and via topical application
      to the ventral surface, CEPA was able to stimulate contact coiling. Within 1 day
      of application of CEPA, the tendrils showed symptoms of senescence. It is
      concluded that ethylene participates in the control of contact coiling stimulated
      by touch, and it is suggested that this control may be exerted via permeability
      changes in the membranes of the motor cells.

PMID- 16657519
TI  - Response of cultivars of soybean to synthetic abscisic Acid.

PMID- 16657520
TI  - Embryo Expansion without Protrusion in Lettuce Seeds.

PMID- 16657521
TI  - Cytokinin-induced Growth Responses by Fenugreek Cotyledons.

PMID- 16657522
TI  - Response of Lemma perpusilla to Periodic Transfer to Distilled Water.
AB  - The flowering of Lemma perpusilla grown on half-strength Hutner's medium with
      sucrose under inductive photo-periods is inhibited in a periodic manner by daily
      transfers to water for short periods of time. The phase of maximal inhibition of
      flowering caused by water treatment is about 1 to 2 hours after the time of
      maximal sensitivity to light pulses. The rhythm of sensitivity to water
      treatments does not persist under continuous blue light. Supplementing the water
      with either Ca(NO(3))(2) or K(2)HPO(4) partially reverses the inhibition of
      flowering, with the first salt being more effective. Supplementation with
      NH(4)NO(3) or MgSO(4) increases the inhibition. The water effect on flowering is
      not observed in plants grown on half-strength Hutner's medium without sucrose.
      The water treatments may act by removing or destroying a crucial precursor for
      photoperiodic induction, with the other conditions modifying permeability. The
      system provides a new technique for investigating the mechanism of photoperiodic
      induction.

PMID- 16657523
TI  - Interactions of rubidium, sodium, and potassium on the nutrition of sugar beet
      plants.
AB  - The effect of Rb on the growth and the development of sugar beet plants (Beta
      vulgaris, var. MS NB1 x NB4) depends on the Rb concentration, the K supply, and
      the relative abundance of Na. Rubidium added either to a low or high K solution
      with or without added Na increased leaf blade size greatly, possibly through an
      effect on phytohormones or through a "partitioning effect" on the distribution of
      carbohydrates, with top growth favored over storage roots.Sodium increased the
      growth of sugar beet plants when they were either K-deficient or adequately
      supplied with K. Sodium or Rb added to a high K solution increased the sucrose
      percentage and total sucrose of the storage roots significantly. Sodium and Rb
      supplied simultaneously to the nutrient solution resulted in synergetic effects
      only at low K supply.Potassium was translocated in mature leaves from the petiole
      to the blade when Na was added to a low K solution, or when Rb was added either
      to a low or a high K solution. Rb + K had little to no effect on Na
      redistribution.

PMID- 16657524
TI  - Enzymic Mechanism of Starch Breakdown in Germinating Rice Seeds: III. alpha
      Amylase Isozymes.
AB  - The formation of amylase isozymes in germinating rice (Oryza sativa) seeds was
      studied by isoelectric focusing on polyacrylamide gel disc electrophoresis. Time
      sequence comparisons of the amylase zymogram were made between extracts from
      gibberellic acid-treated embryoless and embryo-attached half-endosperm of rice
      seeds. In both cases, 4 major and 9 to 10 minor isozyme bands were detectable at
      the maximal stage of the enzyme induction. However, in the embryo-attached half
      seeds, bands started to diminish after the 5th day of incubation, in agreement
      with the results of time sequence analyses of enzyme activities. Nearly identical
      patterns of amylase isozyme bands on a polyacrylamide gel disc electrophoresis in
      combination with isoelectric focusing indicate the intrinsic role of gibberellic
      acid in the starch breakdown in germinating rice seeds. We tentatively assign the
      newly synthesized enzymes to be alpha-amylases based on experimental results
      concerning the lability of the preparation on a prolonged treatment at pH 3.3 and
      the stability on heat treatment for 15 minutes at 70 C.

PMID- 16657525
TI  - Involvement of Ethylene in Picloram-induced Leaf Movement Response.
AB  - The relationship of root-applied 4-amino-3,5,6-trichloropicolinic acid (picloram)
      to ethylene production and the leaf movement response in honey mesquite (Prosopis
      juliflora [Swartz] DC. var. glandulosa [Torr.] Cockerell) and huisache (Acacia
      farnesiana [L.] Willd.) was studied in detail. The threshold and saturation
      levels of exogenous ethylene and root-applied picloram necessary to inhibit leaf
      movement were determined. Internal levels of ethylene in excess of those
      necessary to saturate the leaf movement inhibition response occurred in tops of
      treated plants before and after symptom expression. These internal levels of
      ethylene, while averages for the entire plant tops, probably occur at the
      specific site of action and thus account for the action of picloram in inhibition
      of leaf movement and related responses. Quantitative differences in the leaf
      movement response of both species to picloram and ethylene were observed. In
      huisache alone, a very small change in ethylene levels was necessary to produce a
      major blockage of the leaf movement response, suggesting that the gas may have a
      natural function in that species.

PMID- 16657526
TI  - Changes in Nucleic Acids in Phytochrome-dependent Elongation of the Alaska Pea
      Epicotyl.
AB  - Red light, which produces the physiologically active form of phytochrome (Pfr),
      inhibited epicotyl elongation in intact dark-grown Alaska pea seedlings. This red
      light response was detectable 3 hours after the light treatment and became
      pronounced after 5 hours. The growth inhibition was completely reversed by far
      red light applied immediately after the red or by pretreatment of the seedlings
      with the plant hormone gibberellin A(3).Comparison of the total (32)P-labeled
      nucleic acids from control and red light-treated Alaska pea epicotyls on
      methylated albumin-kieselguhr columns revealed a marked alteration of the pattern
      of nucleic acid synthesis in this plant material with little or no effect on
      total isotope incorporation into nucleic acids. A single 5-minute red light
      perturbation caused a 2-fold stimulation of (32)P incorporation into the tRNA
      fraction while, simultaneously, (32)P incorporation into tenaciously bound RNA
      was reduced to 50% of control levels. Red light treatment had no effect on (32)P
      incorporation into the DNA-RNA, rRNA, or mRNA fractions. Far red light reversed
      the effect of red light on tRNA synthesis but did not restore tenaciously bound
      RNA levels to the control value. Gibberellin A(3) treatment did not cause
      reversal of any of the red light effects on RNA synthesis.These light-induced
      changes in nucleic acids were measurable before any changes in the physiological
      response (epicotyl elongation) could be detected. These results are consistent
      with a phytochrome-mediated differential gene activation mechanism in the Alaska
      pea epicotyl elongation system.

PMID- 16657527
TI  - Compartments and Fluxes of K, NA, and CL in Avena Coleoptile Cells.
AB  - By the compartmental analysis method of MacRobbie and Dainty, and Pitman,
      estimates of K(+), Na(+), and Cl(-) concentrations and fluxes were obtained for
      the cytoplasm and vacuole of coleoptile cells of oat, Avena sativa L. cv.
      Victory. Double labeling was used in experiments with (42)K plus (22)Na and with
      (42)K plus (36)Cl in a complete nutrient solution. At the plasmalemma, according
      to the Ussing-Teorell flux ratio equation, Na(+) is pumped out and Cl(-) is
      actively transported inward. The results with K(+) are less conclusive, but it is
      probably pumped in. At the tonoplast there is an active inward transport of Na(+)
      and probably of K(+), but the status of Cl(-) is uncertain, depending upon
      whether there is an electrical potential difference between the cytoplasm and
      vacuole. The results suggest that ion selectivity resides mostly in the
      plasmalemma. Possible errors in the estimates and interpretations are discussed.

PMID- 16657528
TI  - Endogenous gibberellins and inhibitors in relation to flower induction and
      inflorescence development in the olive.
AB  - Comparative analyses of reproductive and vegetative tissues of the olive (Olea
      europaea L. cv. Manzanillo) for endogenous hormones, particularly inhibitors and
      gibberellin like substances, were made to study the relation between such
      hormones and thermoinduction of flowering. Qualitative and quantitative changes
      in gibberellin-like subtance(s) were observed in lateral buds (potential flower
      buds) but not in leaves or terminal buds (potential vegetative buds) sampled from
      orchard trees at intervals during the winter and spring. At least two types of
      gibberellin-like substances were found in extracts of lateral buds; their levels
      increased progressively during the low temperature induction period, reaching a
      maximum shortly before floral initiation. Two types of inhibitors were extracted
      from buds and leaves. A nonacidic type did not change during the induction stage
      but decreased considerably during the initiation period. An acidic inhibitor,
      which was identified as an abscisic acid-like substance, was present at a
      relatively lower level in lateral (flower) buds than in terminal (vegetative)
      buds during the induction period.It was concluded that winter chilling induces
      flowering in the olive possibly by altering a balance between endogenous
      gibberellins and inhibitors, including abscisic acid.Inflorescence development
      following the winter chilling period was associated with an increase in the level
      of endogenous inhibitors and gibberellins. Shoot growth, however, was correlated
      with a decrease in the inhibitor(s) level. A rise in gibberellin-like activity is
      believed to be a result, not a cause, of shoot growth.

PMID- 16657529
TI  - Quantitative distribution and metabolism of auxin herbicides in roots.
AB  - The internal concentrations of four auxin herbicides- 2,4-dichlorophenoxyacetic
      acid, dicamba, picloram, and naphthaleneacetic acid-were measured in the roots of
      treated pea seedlings. Intact seedlings were immersed in solutions of labeled
      herbicides at concentrations sufficient to produce toxic symptoms (inhibition of
      elongation, radial enlargement, and lateral root proliferation). Measurements of
      volume and herbicide content of segments taken sequentially along the root showed
      that an acropetal concentration gradient of each herbicide was established within
      the root immediately following treatment. Although there was a net loss of
      herbicide in the following 24 hours, the gradient was maintained. Initially, the
      concentration of herbicide in the root tips exceeded that in the external
      medium.In support of the contention that toxic symptoms due to herbicide
      treatment are caused by the presence of unmetabolized chemical at the site of
      action, it was found that metabolism was negligible for all herbicides except
      naphthaleneacetic acid.

PMID- 16657530
TI  - Photoinduced Carotenogenesis in Chlorotic Euglena gracilis.
AB  - Light induces beta-carotene synthesis in streptomycin-bleached Euglena gracilis
      Z. Light-adapted, chemostat-grown cells have up to 10-fold as much beta-carotene
      and 25% more protein than similarly grown, dark-adapted cells. Carotenogenesis
      does not occur under anaerobic conditions or in the presence of diphenylamine,
      cyanide, or cycloheximide. The blue portion of the spectrum (360-560 nm) is most
      active in initiating carotenogenesis. The level of cellular carotenoids is
      influenced by the type of carbon source and to some degree by pH. Phytofluence
      and zeta-carotene are present in dark-grown cells but not in cells grown
      aerobically in white light (360-1120 nm). These pigments, however, were present
      in cells grown in yellow or green light (above 486 nm) or in cells exposed to
      white light anaerobically. The carotenoids are localized in two types of
      structures at the light microscope level. A protoporphyrin was isolated from
      Euglena, and its role as a possible photoreceptor during carotenogenesis is
      suggested.

PMID- 16657531
TI  - Chloroplast composition and structure differences in a soybean mutant.
AB  - A nuclear mutation of Glycine max (soybean) segregates 1:2:1 in regard to
      chlorophyll content. The heterozygous (LG) leaf blade contains about one-half the
      pigment content of the wild type (DG) per gram fresh weight. A lethal yellow (LY)
      type contains about 1 to 2% of the DG leaf pigment values. The chlorophyll a/b
      ratio in the LG is about 5 compared to about 2 in the DG. Protein/leaf values are
      lower in the LG and LY types when compared to DG. The LG plastid lamellae contain
      more protein/chlorophyll, cytochromes/chlorophyll, and quinones/chlorophyll than
      the DG. P(700)/chlorophyll values are similar in the DG and LG types.The
      chlorophyll-depleted LG and LY types had less total acyl lipids per leaf weight
      when compared to the DG type. Similar amounts of sulfolipid and phosphatidyl
      glycerol per protein residue weight were found in the LG and DG plastids;
      however, the monogalactosyl and digalactosyl diglycerides were reduced in the LG
      paralleling the chlorophyll depletion.Thin sections of leaf tissue show similar
      sized LG and DG plastids but reduced grana formation in the LG. The LY has very
      few grana and very small grana compared to either DG or LG. The two
      characteristic particles revealed in higher plant chloroplasts by freeze-etching
      are about 15% smaller in the LG compared to the DG plants.

PMID- 16657532
TI  - Photochemical characteristics in a soybean mutant.
AB  - Chloroplasts were isolated from wild type (DG) and heterozygous mutant (LG)
      soybean (Glycine max) leaves, and various biochemical functions were compared.
      Noncyclic electron transport, and its coupled phosphorylation, cyclic
      phosphorylation and H(+) ion transport in both systems, were 3 to 5 times faster
      in rate (on a chlorophyll basis) in the mutant plastids. On a chloroplast
      lamellar protein basis, the mutant plastid rates were 1.5 to 2.5 times the wild
      type rates.Plastoquinone (PQ) reduction and oxidation (rates and extent) were
      measured by following absorbance changes at 260 nanometers with the repetitive
      flash technique. Mutant plastids have about a 2-fold greater apparent first order
      rate constant for PQ oxidation and a 3- to 5-fold larger pool of rapidly
      reducible PQ. Plastoquinone oxidation has been identified by other workers as the
      rate-limiting step in electron transport. Assuming the PQ oxidation is a first
      order process (d(PQH(2))/dt = k(D)[PQH(2)]t), the observed increase in k(d) for
      the LG (k(d) (LG) approximately 2k(d) (DG)) and the greater steady state amount
      of rapidly turning over PQ, [PQH(2)](LG)>[PQH(2)](DG), could account for the 3-
      to 5-fold greater rates of electron transport and phosphorylation found in the
      mutant chloroplasts.Light saturation for noncyclic photophosphorylation and
      photosystem 2 plus 1 electron transport occurred at similar intensities for both
      LG and DG plastids. Relative quantum requirements extrapolated to zero intensity
      were similar in the LG and DG, although at finite light intensities the LG had a
      better relative quantum efficiency.Ammonium chloride concentrations needed to
      inhibit cyclic photophosphorylation 50% were similar in both LG and DG plastids.
      Nigericin, poly-l-lysine, and chlorotri-n-butyltin, were needed in concentrations
      5 to 10 times greater in the LG to yield 50% inhibition at comparable chlorophyll
      concentrations.

PMID- 16657533
TI  - Effect of the hypocotyl hook on greening in etiolated cucumber cotyledons.
AB  - Four-day-old etiolated cucumber cotyledons (Cucumis sativus, L.) were excised and
      allowed to green in white fluorescent light at 28 C. Cotyledons excised with a
      full hypocotyl hook exhibited a lag phase of 1 hour before entering the rapid
      greening phase, whereas cotyledons excised without any hypocotyl hook exhibited a
      lag phase of 6 hours. Cotyledons excised with varying lengths of hypocotyl hook
      accumulated chlorophyll roughly in proportion to the hook length. When cotyledons
      were excised with a full hook and were partially or totally shielded from light
      with aluminum foil, the samples with the hook covered accumulated more
      chlorophyll than the wholly exposed samples. The samples with the cotyledons
      covered showed no net accumulation of chlorophyll irrespective of hook's exposure
      to light. These data suggest the contribution of some factor or factors by the
      hypocotyl hook which reduce the lag phase during greening.

PMID- 16657534
TI  - Bioassay and attributes of a growth factor associated with crown gall tumors.
AB  - An improved bioassay is described for a factor that promotes tumor growth which
      was first obtained from extracts of pinto bean leaves with crown gall tumors.
      Sixteen primary pinto bean leaves per sample are inoculated with sufficient
      Agrobacterium tumefaciens to initiate about 5 to 10 tumors per leaf and treated
      with tumor growth factor at day 3 after inoculation. The diameters of 30 to 48
      round tumors (no more than 3 randomly selected per leaf) are measured per test
      sample at day 6. Mean tumor diameter increased linearly with the logarithm of the
      concentration of tumor growth factor applied. The tumor growth factor was
      separated by column chromatography from an ultraviolet light-absorbing compound
      previously reported to be associated with fractions having maximal tumor growth
      factor activity. Partly purified tumor growth factor showed no activity in a
      cytokinin bioassay or an auxin bioassay, and negligible activity in gibberellin
      bioassays. Representatives of these three classes of growth factors did not
      promote tumor growth. Extracts from crown gall tumors on primary pinto bean
      leaves, primary castor bean leaves, Bryophyllum leaves, carrot root slices, and
      tobacco stems showed tumor growth factor activity, whereas extracts from healthy
      control tissues did not. Extracts from actively growing parts of healthy pinto
      beans, Bryophyllum, and tobacco, however, showed tumor growth factor activity.
      Tumor growth factor is proposed to be a normal plant growth factor associated
      with rapidly growing tissues. Its synthesis may be activated in nongrowing
      tissues by infection with Agrobacterium sp.

PMID- 16657535
TI  - Gas-Liquid Chromatographic Analysis of Indole-3-acetic Acid Myoinositol Esters in
      Maize Kernels.
AB  - An improved method of fractionating the myoinositol esters of indoleacetic acid
      (IAA) from maize kernels by gas-liquid chromatography has been developed. Mass
      spectrometry was employed as an aid in identification of the esters. Maize
      kernels contain three groups of esters of IAA: (a) IAA myoinositols, (b) IAA
      myoinositol arabinosides, and (c) IAA myoinositol galactosides. Each group has
      three chromatographically distinguishable isomers. The glycosylinositols
      described are unique in that carbon 1 of the sugar is attached to the hydroxyl at
      C-5 of the myoinositol.

PMID- 16657536
TI  - Regulation of sulfate transport in filamentous fungi.
AB  - Inorganic sulfate enters the mycelia of Aspergillus nidulans, Penicillium
      chrysogenum, and Penicillium notatum by a temperature-, energy-, pH-, ionic
      strength-, and concentration-dependent transport system ("permease"). Transport
      is unidirectional. In the presence of excess external sulfate, ATP sulfurylase
      negative mutants will accumulate inorganic sulfate intracellularly to a level of
      about 0.04 m. The intracellular sulfate can be retained against a concentration
      gradient. Retention is not energy-dependent, nor is there any exchange between
      intracellular (accumulated) and extracellular sulfate. The sulfate permease is
      under metabolic control. Sulfur starvation of high methionine-grown mycelia
      results in about a 1000-fold increase in the specific sulfate transport activity
      at low external sulfate concentrations. l-Methionine is a metabolic repressor of
      the sulfate permease, while intracellular sulfate and possibly l-cysteine (or a
      derivative of l-cysteine) are feedback inhibitors. Sulfate transport follows
      hyperbolic saturation kinetics with a Michaelis constant (Km) value of 6 x 10(-5)
      to 10(-4)m and a V(max) (for maximally sulfurstarved mycelia) of about 5
      micromoles per gram per minute. Refeeding sulfur-starved mycelia with sulfate or
      cysteine results in about a 10-fold decrease in the V(max) value with no marked
      change in the Km. Azide and dinitrophenol also reduce the V(max.).

PMID- 16657537
TI  - Investigation of plant water relations with divided root systems of soybean.
AB  - Soybean (Glycine max) was grown with root systems divided between adjacent
      cartons containing nutrient solution or soil. By adding polyethylene glycol
      (Carbowax 6000) to reduce solute potential or withholding water to reduce soil
      matric potential until water absorption from that side stopped, the root xylem
      water potential could be ascertained. Carbowax appeared to increase root
      resistance. An imbalance technique is described with which soil moisture contents
      of adjacent containers were followed individually. The patterns of water
      absorption obtained following repeated additions of water or addition of CaCl(2)
      solutions to one side indicated soil hydraulic conductivity became limiting at a
      soil water potential of -2 bars. A high concentration of CaCl(2) added to one
      side greatly reduced transpiration and produced severe plant injury. With part of
      the root system developing in nutrient solution, growth of roots into and water
      absorption from soil were slow; however, reduction of solute potential in the
      solution side greatly increased water absorption from the soil side.

PMID- 16657538
TI  - Mechanism for the differential translocation of amiben in plants.
AB  - The proportion of the total plant radioactivity present in shoots at the end of a
      24-hour exposure of the roots to 0.5 milligram per liter (14)C-3-amino-2,5
      dichlorobenzoic acid ((14)C-amiben) ranged from 1.4 to 74.3% in 13 species. When
      roots of 10-day-old wheat (Triticum aestivum L. em. Thell., Triumph) and 13-day
      old barnyard grass (Echinochloa crusgalli L. Beauv.) plants were treated with 0.5
      milligram per liter (14)C-amiben for 12 or 24 hours, barnyard grass shoots
      contained at least eight times more of the total plant radioactivity than did
      wheat shoots. In similar experiments with (14)C-2-chloro-4-(ethylamino)-6
      (isopropylamine)-s-triazine ((14)C-atrazine), there were no differences in
      translocation between these two species.The rates of (14)C-amiben absorption into
      the plants and translocation to shoots in both species were constant with time
      for 10 hours. When the bases of excised shoots were exposed to (14)C-amiben, both
      species transported the radioactivity into leaves and metabolized the amiben
      similarly to intact shoot tissues. Amiben was the only radioactive compound
      identified in guttation fluid obtained from (14)C-amiben-treated barnyard grass.
      When treated for 10 hours with (14)C-amiben at concentrations of 0.05 to 200.0
      milligrams per liter, a significant correlation between log [shoot amiben] (in
      amiben equivalents) and log [root amiben concentration] was obtained with no
      species differences.The postulated mechanism for the species differences in (14)C
      amiben translocation is that the tolerant species, wheat, fixes the (14)C-amiben
      in the roots, principally as nontransportable N-(carboxy-2,5
      dichlorophenyl)glycosylamine (N-glucosyl amiben), while only "free" amiben is
      translocated to shoots. Wheat converted more absorbed amiben to N-glucosyl amiben
      or amiben-X than barnyard grass in both roots and shoots.The amiben concentration
      required to inhibit radicle elongation 50% in 4-day-old seedlings was about 50
      milligrams per liter for wheat and 1 milligram per liter for barnyard grass.

PMID- 16657539
TI  - Biogeochemistry of the stable isotopes of hydrogen and carbon in salt marsh
      biota.
AB  - Deuterium to hydrogen ratios of 14 plant species from a salt marsh and lagoon
      were 55 per thousand depleted in deuterium relative to the environmental water.
      Carbon tetrachloride-extractable material from these plants was another 92 per
      thousand depleted in deuterium. This gave a fractionation factor from water to
      CCl(4) extract of 1.147. This over-all fractionation was remarkably constant for
      all species analyzed. Plants also discriminate against (13)C, particularly in the
      lipid fraction. Data suggest that different mechanisms for carbon fixation result
      in different fractionations of the carbon isotopes. Herbivore tissues reflected
      the isotopic ratios of plants ingested. Apparently different metabolic processes
      are responsible for the different degrees of fractionation observed for hydrogen
      and carbon isotopes.

PMID- 16657540
TI  - Biochemical factors affecting protein accumulation in the rice grain.
AB  - Rice grains (Oryza sativa L.) from three varieties and three pairs of lines with
      different protein content were collected at 4-day intervals from 4 to 32 days
      after flowering. The samples were analyzed for protein, free amino nitrogen,
      ribonucleic acid, protease activity, and ribonuclease activity. In addition, the
      capacity of the intact grain to incorporate amino acids was determined for the
      three pairs of lines. The maximal level of free amino nitrogen and the capacity
      of the developing grain to incorporate amino acids were consistently found to be
      higher in the samples with the high protein content in the mature grain. The
      ribonucleic acid content of the grain tended to be higher in the high protein
      samples.

PMID- 16657541
TI  - Lipid composition of cyanidium.
AB  - The major lipids in Cyanidium caldarium Geitler are monogalactosyl diglyceride,
      digalactosyl diglyceride, plant sulfolipid, lecithin, phosphatidyl glycerol,
      phosphatidyl inositol, and phosphatidyl ethanolamine. Fatty acid composition
      varies appreciably among the lipids, but the major ones are palmitic acid, oleic
      acid, linoleic acid, and moderate amounts of stearic acid. Trace amounts of other
      acids in the C(14) to C(20) range were also present. Moderate amounts of
      linolenic acid were found in two strains, but not in a third. The proportion of
      saturated acid is relatively high in all lipids ranging from about a third in
      monogalactosyl diglyceride to three-fourths in sulfolipid. This may be a result
      of the high growth temperature. Lipases forming lysosulfolipid, and
      lysophosphatidyl glycerol are active in ruptured cells; galactolipid is degraded
      with loss of both acyl residues. Thus the lipid and fatty acid composition of
      Cyanidium more closely resembles that of green algae than that of the blue-green
      algae, although there are differences of possible phylogenetic interest.

PMID- 16657542
TI  - Inhibition of Ornithin Carbamyl Transferase from Bean Plants by the Toxin of
      Pseudomonas phaseolicola.

PMID- 16657543
TI  - Tissue distribution of microbody, mitochondrial, and soluble malate dehydrogenase
      isoenzymes.

PMID- 16657544
TI  - Phytochrome and the inductive dark period in coleus.

PMID- 16657545
TI  - Cutin Biosynthesis in Vicia faba Leaves: Effect of Age.

PMID- 16657546
TI  - Extensibility of pericarp tissue in growing citrus fruits.
AB  - The tensile force existing in the pericarp of a growing citrus (Citrus sinensis)
      fruit 17 to 19 centimeters in circumference was sufficiently high to cause a 3%
      shrinkage of the pericarp when it was excised. When a fruit was cut along the
      equator to the central axis, shrinkage of the pericarp resulted in the formation
      of a wedge-shaped gap at the cut. Stretch modulus of the pericarp was determined
      by measuring the force required to stretch excised strips of tissue to 1% longer
      than their excised length. Measurements were made on successive layers of
      pericarp tissue 5 millimeters wide and 1 millimeter thick taken from the fruit
      equator. All layers required more force for extension at lower temperatures and
      high water potentials than at high temperatures and low water potentials. The
      stretch modulus ranged from 0.88 to 2.16 kilograms per square millimeter
      depending upon the layer, temperature, and water potential. The inner layers,
      consisting primarily of mesocarp, had stretch moduli only 60 to 70% as great as
      the outer layer which consisted of exocarp tissue. Measurements of the stretch
      modulus of tissues from the pericarp support the hypothesis that changes in the
      tension existing in the pericarp depend upon conditions in the pericarp and are
      not related to changes in volume or pressure in the juice vesicles.

PMID- 16657547
TI  - Ethylene production of ethyl propylphosphonate, niagara 10637.
AB  - The response of pea seedlings (Pisum sativum var. Alaska) to ethyl
      propylphosphonate is similar to the effects of low levels of ethylene. Since
      ethyl propylphosphonate generates ethylene when exposed to oxygen in combination
      with a reduced metal ion, it seems probable that its plant growth-retardant
      properties are due to ethylene.

PMID- 16657548
TI  - Abscission: movement and conjugation of auxin.
AB  - A 1-hour application of indole-3-acetic acid to bean (Phaseolus vulgaris L. cv.
      Red Kidney) explants inhibited abscission for an 8-hour aging period. Use of
      indole-3-acetic acid-(14)C showed that the applied indole-3-acetic acid was
      conjugated within explant tissue and that this conjugation mechanism accounts for
      loss of effectiveness of indole-3-acetic acid in inhibiting abscission after 8
      hours. Reapplication of indole-3-acetic acid to an explant at a later time,
      before the induced aging requirement was completed reinhibited abscission. 2,4
      Dichlorophenoxyacetic acid, which is not destroyed or conjugated by this system,
      did not lose its ability to inhibit abscission. It was concluded that indole-3
      acetic acid destruction is one of the processes involved in the aging stage of
      abscission in explants.

PMID- 16657549
TI  - Studies on seeds: v. Microbodies, glyoxysomes, and ricinosomes of castor bean
      endosperm.
AB  - Glyoxysomes, a form of microbody, are present in castor bean endosperm during the
      first 8 days of seed germination. They have a "typical" microbody form and are
      shown histochemically to contain catalase. The catalase label is distributed
      throughout the microbody and is not an exclusive feature of the crystalline or
      amorphous core.Castor bean endosperm contain a second cytosome, only slightly
      larger than the glyoxysomes, which is bound by a rough-surfaced membrane and
      which does not label for catalase. We have not observed these cytosomes in other
      tissues, suggesting that they may have a specific cellular function
      characteristic of castor bean endosperm.

PMID- 16657550
TI  - Light-induced Development of Polyribosomes and the Induction of Nitrate Reductase
      in Corn Leaves.
AB  - Nitrate reductase activity was induced by nitrate in green corn (Zea mays) leaves
      in either light or darkness. The induction process required oxygen in darkness
      but not in light. A light treatment was required before the enzyme could be
      induced in etiolated leaves.The capacity for nitrate reductase induction by
      nitrate was positively correlated with the level of cytoplasmic polyribosomes
      under a variety of experimental conditions. (a) Light-grown leaves contained high
      levels of polyribosomes (84% of the total population, most of which were of the
      80 S type); similarly high levels of nitrate reductase activity were induced. (b)
      The level of polyribosomes and the ability to form nitrate reductase activity
      rapidly decreased in light-grown leaves following transfer to an anaerobic
      environment in the dark; both parameters were maintained at a high level when
      light-grown leaves were kept in the light under anaerobic conditions. (c) The
      ability of light-grown leaves, previously placed in darkness under nitrogen to
      dissociate polyribosomes to monoribosomes, to form nitrate reductase activity
      again correlated with the level of reformed polyribosomes following transfer of
      the leaves back to light. (d) Etiolated leaves contained a low level of
      cytoplasmic polyribosomes (27%), and nitrate reductase activity was induced
      following exposure to light only after a lag of 2 to 4 hours. During this lag
      period there was a marked increase in the level of polyribosomes.The ability of
      leaves to form nitrate reductase activity and the level of polyribosomes also
      correlated with the level of in vitro incorporation of amino acids into protein
      by the isolated ribosome preparations. Thus, the apparent requirement of light
      for nitrate reductase induction in etiolated leaves seems not to be specific.
      Rather an influence of light upon the development of an active protein
      synthesizing apparatus as evidenced by the state of polyribosomes is
      indicated.The results also show that energy from photosynthetic phosphorylation
      can be used to maintain cytoplasmic polyribosomes (and thus to drive cytoplasmic
      protein synthesis), at least under anaerobic conditions.

PMID- 16657551
TI  - Effect of environmental factors on cuticular transpiration resistance.
AB  - Measurements of the various diffusive resistances to water vapor transport within
      the leaves of sunflower plants (Helianthus annuus) growing in a controlled
      environment chamber, were used to calculate values of cuticular resistance under
      a range of environmental conditions. Cuticular resistance to water loss was found
      to be inversely related to the relative humidity of the surrounding air, and it
      is suggested that such a mechanism would form a useful adaptation to arid
      conditions, enabling plants to maintain a more favorable internal water balance.

PMID- 16657552
TI  - Synthesis and Transport of Hydroxyproline-rich Components in Suspension Cultures
      of Sycamore-Maple Cells.
AB  - Plant cell walls contain a glycoprotein rich in hydroxyproline. To determine how
      Acer pseudoplatanus L. cells transport this glycoprotein to the wall, the pulse
      chase technique was used to follow changes in specific radio-activity of
      hydroxyproline and proline in isolated, mitochondrial, Golgi, microsomal, soluble
      protein, and wall fractions. The turnover rates or changes in specific
      radioactivity of cytoplasmic hydroxyproline in these cell fractions indicated
      that the bulk of this hydroxyproline was transferred not by the Golgi apparatus
      but by a smooth membranous component.

PMID- 16657553
TI  - Glucose metabolism of various tissues of pear buds.
AB  - Various tissues in flower buds of Pyrus calleryana Decne. differ in their
      metabolic activity. Brown outer scales utilized more exogenously supplied
      glucose, particularly through the pentose phosphate pathway, than did the central
      axes and the green inner scales. They also contained more endogenous reducing
      sugars, and glucose leaked out more readily from the brown scales than from the
      other tissues. In contrast, respiration of the central axes was nine times as
      great as that of the brown scales, and two to four times as much glucose was
      metabolized through glycolysis. Membranes of the central axes were less permeable
      to glucose. Because the brown scales are 75% of the dry weight of the bud, they
      dominate its pattern of glucose metabolism.

PMID- 16657554
TI  - A technique for the axenic culture and feeding of excised woody stems.

PMID- 16657555
TI  - Temporary inhibition of translocation velocity and mass transfer rate by petiole
      cooling.

PMID- 16657556
TI  - A Simple Technique for the Rapid Determination of Plant CO(2) Compensation
      Points.

PMID- 16657557
TI  - Detergent Fractionation of Glutaraldehyde-fixed Spinach Thylakoids.

PMID- 16657558
TI  - The effect of light quality on glycolate formation and excretion in algae.

PMID- 16657559
TI  - Ultrastructural changes of embryos in wheat infected with storage fungi.

PMID- 16657560
TI  - Peptide hydrolase C in germinating barley.

PMID- 16657561
TI  - Recipe for ferric salts of ethylenediaminetetraacetic Acid.

PMID- 16657562
TI  - Host-Pathogen Interactions: II. Parameters Affecting Polysaccharide-degrading
      Enzyme Secretion by Colletotrichum lindemuthianum Grown in Culture.
AB  - The effect of a number of physiological variables on the secretion of
      polysaccharide-degrading enzymes by culture-grown Colletotrichum lindemuthianum
      (Saccardo and Magnus) Scribner was determined. The number of spores used to
      inoculate cultures grown on isolated bean hypocotyl cell walls affects the time
      after inoculation at which enzyme secretion occurs, but has no significant effect
      on the maximal amount of enzyme ultimately secreted. Cell walls isolated from
      bean leaves, first internodes, or hypocotyls (susceptible to C. lindemuthianum
      infection), when used as carbon source for C. lindemuthianum growth, stimulate
      the fungus to secrete more alpha-galactosidase than do cell walls isolated from
      roots (resistant to infection). The concentration of carbon source used for
      fungal growth determines the final level of enzyme activity in the culture fluid.
      The level of enzyme secretion is not proportional to fungal growth; rather,
      enzyme secretion is induced. Maximal alpha-galactosidase activity in the culture
      medium is found when the concentration of cell walls used as carbon source is 1%
      or greater. A higher concentration of cell walls is necessary for maximal alpha
      arabinosidase activity. Galactose, when used as the carbon source, stimulates
      alpha-galactosidase secretion but, at comparable concentrations, is less
      effective in doing so than are cell walls. Polysaccharide-degrading enzymes are
      secreted by C. lindemuthianum at different times during growth of the pathogen on
      isolated cell walls. Pectinase and alpha-arabinosidase are secreted first,
      followed by beta-xylosidase and cellulase, then beta-glucosidase, and, finally,
      alpha-galactosidase.

PMID- 16657563
TI  - A unique adenosine diphosphoglucose pyrophosphorylase associated with maize
      embryo tissue.
AB  - A comparison of heat stabilities and various kinetic properties between the
      adenosine diphosphoglucose pyrophosphorylases isolated from endosperm and embryo
      tissues from starchy maize seeds indicates that the adenosine diphosphoglucose
      pyrophosphorylase associated with the embryo is distinct from the enzyme isolated
      from the endosperm. The embryo enzyme is more stable to incubation for 5 minutes
      at 60 C while the endosperm enzyme is labile to this treatment. Both enzymes are
      activated by glycerate-3-P. The embryo enzyme is more sensitive to inhibition by
      phosphate than is the endosperm enzyme. Glycerate-3-P, which reverses the
      inhibition of the endosperm enzyme by phosphate, has little effect on the
      phosphate inhibition of the embryo enzyme. Other kinetic studies distinguish the
      two enzymes.

PMID- 16657564
TI  - Content of adenosine phosphate compounds in pea roots grown in saline media.
AB  - The levels of ATP, ADP and AMP, the activity of phosphatases, and the ability for
      oxidative phosphorylation were studied in roots of pea (Pisum sativum) plants
      grown in media salinized either with NaCl or Na(2)SO(4). In response to salinity,
      the ATP level in the roots decreased, whereas the ADP level increased slightly.
      As a result, the ADP:ATP ratio in the tissue increased with increasing salinity
      in the growth medium. The AMP level in the tissue was not affected by
      salinity.Phosphatase activity (using p-nitrophenyl phosphate and ATP as
      substrates), in the soluble and in the mitochondrial fractions from roots grown
      in NaCl-salinized media, was considerably higher than in the control roots. In
      the mitochondrial fraction of the roots grown in Na(2)SO(4)-salinized media, such
      an increase was not observed.The phosphorylating activity of mitochondria was
      depressed by the two types of salinity, but was more sensitive to NaCl salinity.
      In mitochondrial suspensions prepared from roots exposed to salinity, practically
      no phosphorylation could take place if nicotinamide adenine dinucleotide was
      omitted from the reaction mixture; but even when added, the restoration of
      phosphorylative ability was not complete. Addition of NaCl to the reaction
      mixture did not affect the activity of the phosphatases. Addition of Na(2)SO(4)
      to the reaction mixture depressed, in some cases, the activity of the acid
      phosphatase. Phosphorylative activity was affected, however, by both types of
      salinity: presence of either NaCl or Na(2)SO(4) at - 1 atm in the reaction
      mixture increased phosphorylative activity, and higher concentrations (-3 and -5
      atm) depressed it.

PMID- 16657565
TI  - Assay of adenosine 5-triphosphate sulfurylase by pyrophosphate exchange.
AB  - The sulfate-dependent pyrophosphate exchange reaction has been re-examined and
      confirmed. Standard assay conditions for measuring ATP sulfurylase by sulfate
      dependent pyrophosphate exchange are described and some properties of the enzyme
      (measured in crude dialyzed extracts) are reported. This method has many
      advantages over the well established molybdate method.

PMID- 16657566
TI  - The Fate of l-Phenylalanine Fed to Germinating Pea Seeds, Pisum sativum (L.) var.
      Alaska, during Imbibition.
AB  - Radioactive l-phenylalanine-l-(14)C or -U-(14)C was fed to pea seeds during
      imbibition. More than 95% was imbibed. Less than 1% of the radioactivity was
      respired as CO(2). Of the radioactivity taken into the embryos, 80% was still in
      the cotyledons by 3 days. About half of this was unchanged phenylalanine: 5%
      free, 10 to 20% in soluble proteins, 1 to 6% in cell wall proteins, and 14%
      released by mild acid hydrolysis. No other radioactive amino acid was found.
      About 0.3% of the radioactivity was identified as free caffeic, ferulic, and
      coumaric acids or their glycosides, and a further 5% was released by mild acid
      hydrolysis into a phenolic acid fraction. About half of the radioactivity in the
      cotyledons was lost in the fractionation procedures.About 20% of the
      radioactivity was found in the shootroot axes to which it had been translocated.
      Phenylalanine accounted for nearly all the identifiable radioactivity: about 1%
      free, 1 to 3% in soluble proteins, 1 to 5% in cell wall proteins, and 1% bound to
      insoluble fractions from which it was released by mild acid hydrolysis. About 1%
      was released into a phenolic acid fraction. About half of the radioactivity in
      the shoot-root axes was lost in the fractionation procedures.

PMID- 16657567
TI  - Preparation and purification of glucanase and chitinase from bean leaves.
AB  - Glucanase (endo-beta-1, 3-glucan 3-glucanohydrolase, EC 3.2.1.6, laminarinase,
      callase) and chitinase (poly-beta-1, 4-[2-acetamido-2-deoxy] -d-glucoside
      glycanohydrolase, EC 3.2.1.14) were extracted from ethylene-treated bean
      (Phaseolus vulgaris L. cv. Red Kidney) leaves and purified on hydroxyapatite and
      carboxymethyl Sephadex columns. The glucanase prepared was homogeneous as judged
      by analytical centrifugation data, electrophoresis, and antibody-antigen
      reactions. On the basis of gel filtration, antibody-antigen reactions, and amino
      acid analysis, the molecular weight was estimated to be between 11,500 and
      12,500. However, ultracentrifugation gave a higher estimate of 34,000. The
      glucanase had an isoelectric point near pH 11 and was specific for beta-1, 3
      linkages. The chitinase was only partially purified as judged by electrophoretic
      behavior.

PMID- 16657568
TI  - A Lipid Requirement for Photosystem I Activity in Heptane-extracted Spinach
      Chloroplasts.
AB  - A lipid requirement for photosystem I activity in Spinacia oleracea chloroplasts
      has been characterized. The transfer of electrons from tetramethyl-p
      phenylenediamine through the chloroplast photosystem to viologen dye was used as
      an assay of photosystem I activity. Activity is diminished by prolonged heptane
      extraction and is partially restored by readdition of the extracted lipid.
      Extracted chloroplasts require plastocyanin for maximal restoration of activity.
      The effect of lipid extract in restoration is partially replaced by triglycerides
      containing unsaturated, C(18) fatty acids. Various potential redox carriers which
      occur naturally in chloroplasts do not substitute for extracted lipid. Galacto
      lipids, sulfolipids, and phospholipids are not involved in the restoration of
      activity.

PMID- 16657569
TI  - On the Role of Manganese in Photosynthesis: Kinetics of Photoinhibition in
      Manganese-deficent and 3-(4-Chlorophenyl)-1, 1-dimethylurea-inhibited Euglena
      gracilis.
AB  - Euglena gracilis (Klebs) cultures were grown under conditions where limitation in
      supply of manganese limited chlorophyll content much more than growth. Although
      the initial rates of photosynthetic oxygen evolution were not affected by the
      level of manganese, photoinhibition in high intensity light was markedly
      influenced. All cultures showed first order kinetics for photoinhibition, with
      the half-time exponentially related to the Mn concentration in the medium.
      Treatment with 3-(4-chlorophenyl)-1, 1-dimethylurea (CMU) also increased the rate
      of photoinhibition. Manganese-deficient cells were also more sensitive to CMU
      inhibition of photosynthesis. The similar effects on photoinhibition of manganese
      deficiency and of CMU treatment and the protective action of manganese against
      photoinhibition and CMU poisoning are interpreted to indicate a site of action of
      manganese on the reducing side of photosystem II, close to the CMU-sensitive
      site. This manganese-affected site may represent a secondary structural or
      metabolic consequence of manganese deficiency, not necessarily involved in
      quantum yields of oxygen.

PMID- 16657570
TI  - Inhibition of carotenoid synthesis as a mechanism of action of amitrole,
      dichlormate, and pyriclor.
AB  - Amitrole (3-amino-s-triazole), dichlormate (3,4-dichlorobenzyl methylcarbamate),
      and pyriclor (2,3,5-trichloro-4-pyridinol) inhibited normal carotenogenesis in
      etiolated wheat (Triticum aestivum L. var. Coker 65-20) seedlings. Carotenoid
      precursors accumulated in treated plants. In dichlormate-treated plants, zeta
      carotene accumulated, whereas phytofluene, phytoene, and zeta-carotene
      accumulated in amitrole- and pyriclor-treated plants. None of the herbicides
      interfered with protochlorophyllide synthesis or its conversion to chlorophyllide
      when etiolated plants were illuminated. Chlorophyll accumulated in treated plants
      exposed to light at 60 foot candles, but was unstable and partially destroyed by
      illumination at 4000 foot candles. These data suggest that the phytotoxicity of
      amitrole, pyriclor, and dichlormate is due to inhibition of the synthesis of
      carotenoids and to the consequent photodestruction of chlorophyll and chloroplast
      disruption.

PMID- 16657571
TI  - Isolation of Mesophyll Cells and Bundle Sheath Cells from Digitaria sanguinalis
      (L.) Scop. Leaves and a Scanning Microscopy Study of the Internal Leaf Cell
      Morphology.
AB  - A technique is described for the separation of mesophyll and bundle sheath cells
      from Digitaria sanguinalis leaves and evidence for separation is given with light
      and scanning electron micrographs. Gentle grinding of fully differentiated leaves
      in a mortar releases mesophyll cells which are isolated on nylon nets by
      filtration. More extensive grinding of the remaining tissue yields bundle sheath
      strands which are isolated by filtration with stainless steel sieves and nylon
      nets. Further grinding of bundle sheath strands in a tissue homogenizer releases
      bundle sheath cells which are collected on nylon nets. Percentage of purity
      derived from cell counts and yield data on a chlorophyll basis are given.The
      internal leaf cell morphology is presented in scanning electron micrographs and
      compared with light micrographs of fully-differentiated D. sanguinalis leaves. In
      leaves of plants which possess the C(4)-dicarboxylic acid cycle of
      photosynthesis, the relationship of leaf morphology to photosynthesis in
      mesophyll and bundle sheath cells is considered, and the hypothesis is presented
      that as atmospheric CO(2) enters a leaf about 85% is fixed by the C(4)
      dicarboxylic acid cycle in the mesophyll cells and 10 to 15% is fixed by the
      reductive pentose phosphate cycle in the bundle sheath cells.A technique also is
      given for the isolation of mesophyll cells from spinach leaves.

PMID- 16657572
TI  - Structure and distribution of chloroplasts and other organelles in leaves with
      various rates of photosynthesis.
AB  - The ultrastructure and distribution of chloroplasts, mitochondria, peroxisomes,
      and other cellular constituents have been examined in cross sections of leaves
      from plants with either high or low photosynthetic capacity. Photosynthetic
      capacity of a given plant cannot be correlated with the presence or absence of
      grana in bundle sheath cell chloroplasts, the presence or absence of starch
      grains in bundle sheath or mesophyll cell chloroplasts, the chloroplast size in
      bundle sheath or mesophyll cells, or the location of chloroplasts within bundle
      sheath cells. We conclude that the number and concentration of chloroplasts,
      mitochondria, and peroxisomes in bundle sheath cells is the most reliable
      anatomical criterion presently available for determining the photosynthetic
      capacity of a given plant.

PMID- 16657573
TI  - Some characteristics of the uptake of glutamine by corn scutellum.
AB  - Slices of corn scutellum were used to study amino acid uptake, a natural function
      of this tissue. The uptake of glutamine was found to be inhibited by several
      monovalent cations. The accompanying anion did not affect the inhibition.
      Divalent cations stimulated glutamine uptake, particularly at high glutamine
      concentrations. The inhibition by monovalent cations was reversed by divalent
      cations.There was a broad pH optimum (4.3-5.2), and a wide range of pH values
      over which substantial rates of glutamine uptake were observed (3-7).Seventeen
      protein amino acids were tested for their effects on glutamine uptake. l-Alanine,
      l-cysteine, l-glutamic acid, glycine, l-serine, and l-methionine were the only
      inhibitory amino acids. The inhibition by alanine and methionine was overcome at
      high glutamine concentrations whereas the inhibition by monovalent cations was
      not. The inhibition by amino acids was not reversed by divalent cations. d
      Alanine and d-methionine had no effect on glutamine uptake.High concentrations of
      sucrose (0.5 m) did not affect glutamine uptake. Thus, osmotic shock did not
      cause a dissociation of a transport protein from a membrane. Mannose inhibited
      glutamine uptake but glucose, galactose, and fructose did not. In addition to
      respiratory inhibitors, N-ethylmaleimide inhibited glutamine uptake. Ouabain did
      not affect glutamine uptake.

PMID- 16657574
TI  - Ethylene-induced Rough Endoplasmic Reticula in Abscission Cells.

PMID- 16657575
TI  - A translocatable cold hardiness promoter.

PMID- 16657576
TI  - Multisample enzyme extraction from cultured plant cell suspensions.
AB  - Operational and constructional details are given of an apparatus which permits
      simultaneous enzyme extraction from up to 16 cell samples under standardized
      conditions. The main advantages of the method are: (a) individual samples remain
      in the same container throughout the whole operation; (b) the samples can be
      stirred continuously and uniformly during extraction; (c) rapid changes of
      extractant are facilitated by a simple draining operation; (d) the extraction
      temperature can be strictly controlled. The method is rapid, efficient, and
      reproducible in extracting a number of enzymes from cultured rose cells. Other
      uses of the apparatus are discussed, particularly in relation to the extraction
      of protein, nucleic acids, and some low molecular weight materials.

PMID- 16657577
TI  - Gluconeogenesis in the castor bean endosperm: I. Changes in glycolytic
      intermediates.
AB  - The control points of the Embden-Meyerhof-Parnas pathway in germinating castor
      bean (Ricinus communis) endosperms are sought in two ways: (a) by measuring the
      amounts of various glycolytic intermediates at intervals during the germination;
      (b) by determining the crossover points appearing during anoxia.A significant
      departure from thermodynamic equilibrium between substrates and products is found
      at the level of fructose 1,6-diphosphatase and phosphofructokinase. A definite
      shift of this ratio is observed at the onset of active gluconeogenesis. The
      concentrations of phosphoenolpyruvate and 3-phosphoglyceric acid increase at the
      same time. Another departure from the expected equilibrium is also observed at
      the level of the pyruvate kinase.The imposition of anoxia on 5-day-old endosperms
      reveals two crossover points, at the level of the same enzymes. It is therefore
      concluded that they regulate the glycolytic flow.The maximal glycolytic flow,
      however, is only 1/10 of the gluconeogenic one. To account for this high
      gluconeogenic efficiency, it is postulated that gluconeogenesis and glycolysis
      occur in separate intracellular regions. The consistent departure from
      equilibrium between adenylates observed during the early stages of anoxia
      supports the concepts that the pools of glycolytic and gluconeogenic
      intermediates are indeed compartmented and that the two processes are
      independently regulated.

PMID- 16657578
TI  - Action of kinetin on cotyledons of fenugreek.
AB  - Isolated cotyledons of fenugreek (Trigonella foenum graecum L.), which respond
      rapidly and specifically to the application of cytokinins with stimulated
      expansion, have been used to study the primary action of kinetin. Gross chemical
      analysis showed that ribonucleic acid increased within 24 hours in response to
      kinetin application. 8-Azaguanine inhibited both kinetin-induced expansion and
      RNA synthesis; 5-fluorodeoxyuridine inhibited only the RNA synthesis.Cotyledons
      produced nitrate reductase activity in response to 20 mm nitrate only in the
      presence of either light or kinetin and especially in the presence of both.
      Abscisic acid and inhibitors of RNA and protein synthesis depressed this
      response. Inhibitors affecting chloroplast development and function did not
      reduce the response in the presence of light and kinetin.In vitro incorporation
      of (14)C-l-leucine and (14)C-l-phenyl-alanine into protein by various
      recombinations of microsomal and 160,000g supernatant fractions varied according
      to the pretreatment which the cotyledons had received before the preparation of
      the fractions. Stimulatory effects were mainly associated with the microsomal
      fractions.The formation of leucine-, valine-, and tyrosine-tRNA complexes by high
      speed supernatant fractions from differently pretreated cotyledons was also
      compared. The sharp stimulation of the process by adding tRNA was found to be
      independent of the kind of preincubation that the cotyledons used for the tRNA
      extraction had received.It is concluded that the evidence is not in favor of
      kinetin correcting specific tRNA deficiencies. Kinetin removes a limitation that
      prevents the synthesis of RNA and genome expression.

PMID- 16657579
TI  - The effect of water stress on indoleacetic Acid oxidase in pea plants.
AB  - Activity of indoleacetic acid oxidase was shown to increase following a period of
      water stress. Two fractions of indoleacetic acid oxidase were extracted from
      plant extracts. Similarly, two protein peaks (determined by ultraviolet
      absorption) were isolated. One peak, associated with an indoleacetic acid oxidase
      peak, increased following water stress. The second peak, not associated with
      extractable indoleacetic acid oxidase, decreased after water stress. The results
      are discussed in terms of general growth effects.

PMID- 16657580
TI  - Endogenous Short Period Rhythms in the Movements of Unifoliate Leaves of
      Phaseolus angularis Wight.
AB  - Rhythmic rotational movements with the midvein as the axis have been observed in
      the unifoliate leaves of Phaseolus angularis Wight grown under controlled
      environmental conditions with continuous light. The mean period of this movement
      for all leaves was 53.2 +/- 4.3 minutes and remained constant as the leaf
      matured, except after removal of the apical meristem and emerging trifoliate leaf
      when the period increased by about 5 minutes. The amplitude of the movement also
      remained constant as the leaf matured. These rotational movements were pronounced
      when the leaf blade was in a horizontal position and were not evident during the
      downward or "sleep" movements of the leaf. This movement began 3 days after leaf
      unfolding and continued for at least 6 days. It was most pronounced at the time
      of inflection of the leaf length growth curve after the logarithmic phase of
      growth.

PMID- 16657581
TI  - Abscission: the phytogerontological effects of ethylene.
AB  - The role of ethylene in the aging of bean (Phaseolus vulgaris L. cv. Red Kidney)
      petiole abscission zone explants was examined. The data indicate that ethylene
      does accelerate aging in addition to inducing changes in break strength.
      Application of ethylene during the aging stage (stage 1) promoted abscission when
      followed by a second ethylene treatment during the cell separating stage (stage
      2). The half-maximal effective concentration of ethylene to induce aging was
      around 0.3 microliter per liter; 10 microliters per liter was a saturating dose.
      CO(2) reversal of ethylene action during stage 1 was incomplete and gave
      ambiguous results. CO(2) (10%) reversed the effect of 10 microliters per liter
      ethylene but not 1 microliter per liter ethylene. The possibility that ethylene
      not only accelerated aging but was also a requirement for it was tested, and
      experimental evidence in favor of this idea was obtained. It was concluded that
      ethylene plays a dual role in the abscission of bean petiole explants: a
      phytogerontological effect and a cellulase-inducing effect.

PMID- 16657582
TI  - Pyrimidine metabolism in cotyledons of germinating alaska peas.
AB  - Cotyledons from Pisum sativum L. cv. Alaska seeds were excised 12, 36, 108, 132,
      and 156 hours after imbibition in aerated distilled water. They were then
      incubated under aseptic conditions for 6 hours in solutions containing either
      uridine-2-(14)C or orotic acid-6-(14)C. Uridine was more extensively degraded to
      (14)CO(2) at all germination stages than was orotate, and these rates remained
      essentially constant at each stage. Incorporation of each compound into RNA
      increased about 2-fold from the 12th to the 156th hour, although the total RNA
      present decreased slightly over this interval. Paper chromatography of soluble
      labeled metabolites produced from orotate showed that the capacity to metabolize
      this pyrimidine increased markedly as germination progressed. Radioactivity in
      uridine-5'-P, uridine diphosphate-hexoses, and uridine diphosphate increased
      most, while smaller or less consistent increases in uridine, uracil, uridine
      triphosphate, and an unidentified UDPX compound were also observed. The data
      suggest that orotate metabolism was initially limited by orotidine-5'-phosphate
      pyrophosphorylase or by 5-phosphoribosyl-1-pyrophosphate. Incorporation of
      uridine into RNA appeared to be limited at the earliest germination periods by
      conversion of uridine-5'-P to uridine diphosphate. Thus, during the 1st week of
      germination the orotic acid pathway and a salvage pathway converting uridine into
      RNA become activated.

PMID- 16657583
TI  - Electrical potential differences in cells of barley roots and their relation to
      ion uptake.
AB  - Single cell electropotentials of barley (Hordeum vulgare L., cv. ;Compana') root
      cortex were measured at different external concentrations of KCl in the presence
      of Ca(2+). The roots were low in salt from seedlings grown on 0.5 mm aerated
      CaSO(4) solution. Thus, the conditions were equivalent to those used to define
      the dual mechanisms found with radioactive tracer-labeled ion uptake. In 0.5 mm
      CaSO(4) alone, there is an increase with time of cell negativity from about -65
      millivolts 15 minutes after cutting segments to about -185 millivolts in 6 to 8
      hours. Two possible hypotheses, not mutually exclusive, are offered to explain
      this aging effect: that cutting exposes plasmodesmata which are leaky initially
      but which seal in time, and that some internal factors, e.g., hormones diffusing
      from the apex, have a regulatory effect on the cell potential, an influence which
      becomes dissipated in isolated segments and permits the development of a higher
      potential difference. In any case changes in selective ion transport must be
      involved. The cell potentials at KCl concentrations above 2.0 mm are more
      negative than would be expected for a passive diffusion potential. It is
      suggested that this discrepancy may be due to an electrogenic pump or to a higher
      K(+) concentration in the cytoplasm than in the remainder of the cell, or perhaps
      to both. Whether there is a clear relationship between cell potential and
      mechanisms 1 and 2 of cation transport depends upon whether the cell potentials
      of freshly cut or of aged tissue represent the values relevant to intact roots.

PMID- 16657584
TI  - Dissociation of ribosomes and seed germination.
AB  - Ribosomes from rice embryos (Oryza sativa) were dissociated into ribosomal
      subunits in vitro by systematic reduction of the Mg(2+) concentration. Ribosomes
      from imbibed (28 C) embryos were more easily dissociated than those from
      nonimbibed embryos. This was not observed with ribosomes from either imbibed,
      nonviable embryos, or from embryos imbibed at 0 C. Ribosomes from embryos which
      had been imbided and subsequently dehydrated resembled ribosomes from nonimbibed
      embryos in their resistance to dissociation. The change in the resistance to
      dissociation was essentially complete after the first 20 minutes of imbibition at
      28 C, and accompanied activation in vivo of protein synthesis as determined by
      amino acid incorporation in vitro. Ribosomes from either imbibed or nonimbibed
      embryos could be dissociated into subunits by 0.5 m KCl. These subunits were
      separated by density gradient centrifugation, and, if recombined, were active for
      polyphenylalanine synthesis in vitro. The individual subunits prepared from
      nonimbibed embryos could be replaced by the corresponding subunit fraction from
      imbibed embryos without loss of capacity to support polyphenylalanine synthesis.
      The change in the ease of dissociation of ribosomes appears to be a physiological
      process, and its possible relationship to the initiation of protein synthesis
      during seed germination is discussed.

PMID- 16657585
TI  - Cytokinin Activity in Water-stressed Shoots.
AB  - Water stress applied to the plant shoot through enhanced evaporative demands
      reduced cytokinin activity in extracts of xylem exudate and leaves. This
      reduction resembled the changes in cytokinin activity caused by water stress
      applied to the root. Cytokinin activity in detached wilting leaves decreased
      rapidly. Recovery took place after several hours in a humid chamber. Experiments
      with (14)C-kinetin indicated that the mechanism of the inactivation and its
      reversal involve a chemical transformation of the cytokinin molecule.

PMID- 16657586
TI  - Induction of Cold Acclimation in Cornus stolonifera Michx.
AB  - A warm (20 to 15 Celsius day or night) preconditioning treatment enhanced cold
      acclimation of Cornus stolonifera bark under short-day conditions when plants
      were preconditioned for at least 4 weeks. Warm preconditioning inhibited the
      acclimation of plants subjected to long photoperiods. Removing leaves from plants
      exposed to low temperatures and short days inhibited acclimation. Removal of buds
      did not affect acclimation. Plants did not acclimate unless they were exposed to
      at least 4 weeks of short photoperiods prior to defoliation. Plants began to
      acclimate to cold at the time of growth cessation but not before. When half of
      the leaves were removed from plants, the defoliated and foliated branches both
      acclimated as well as branches on completely foliated plants. Girdling the phloem
      between foliated and defoliated branches prevented acclimation of the latter
      regardless of the position of the girdle in relation to the root system and the
      defoliated branch. When all of the leaves of plants were covered with aluminum
      foil to exclude light after 0 or 4 weeks of exposure to short days, the results
      resembled a defoliation study, i.e., plants with leaves covered at the start of
      the experiment failed to acclimate, and those covered after 4 weeks acclimated to
      some extent but less than uncovered control plants. Under longday conditions
      plants with all leaves covered failed to acclimate, and plants with none or half
      of their leaves covered acclimated equally and to a limited extent. Under short
      day conditions, however, the covered branches of partially covered plants
      acclimated more than their uncovered counterparts or branches of totally
      uncovered plants.

PMID- 16657587
TI  - Effect of indoleacetic Acid and hydroxyproline on isoenzymes of peroxidase in
      wheat coleoptiles.
AB  - Indoleacetic acid at 0.017 millimolar inhibited the formation of three peroxidase
      isoenzymes in both soluble and wall-bound enzyme fractions of wheat coleoptile
      (Triticum vulgare) tissue. Hydroxyproline at 1 millimolar prevented the
      indoleacetic acid-induced inhibition. Indoleacetic acid oxidase activity in the
      soluble fraction was decreased by indoleacetic acid and was restored by
      hydroxyproline. Most of the indoleacetic acid oxidase activity was located in the
      electrophoretic zones occupied by two of the peroxidase isoenzymes influenced by
      indoleacetic acid and hydroxyproline. At least part of the effect of
      hydroxyproline on auxin-induced elongation of coleoptile tissue may be through
      control of auxin levels by indoleacetic acid oxidase.

PMID- 16657588
TI  - Effect of sink region anoxia on translocation rate.
AB  - Translocation rate, ATP level, and CO(2) production of a developing leaf (sink
      leaf) were studied in sugar beet (Beta vulgaris) plants prior to and during
      anaerobic treatment of the sink leaf. Within 3 to 5 minutes after onset of
      treatment with a N(2) atmosphere, translocation into the sink leaf decreased to
      near zero and then recovered to a level of about 50% of the control over the next
      2 hours. A decline in CO(2) output and ATP levels coincided with the attainment
      of the new translocation rate. All three quantities returned to near control
      levels within 60 to 120 minutes after the sink leaf was returned to air. Swelling
      and ultrastructural changes in mitochondria coincided with the observed ATP level
      changes during inhibition and recovery periods. The first phase of marked
      inhibition of translocation did not coincide with low ATP level and appeared to
      be caused by decreased membrane permeability during the transition to anaerobic
      metabolism, possibly as a result of a temporary build up of toxic products. The
      correlation between ATP level and translocation rate suggests that ATP-dependent
      active transport in the sink leaf augments the driving force for translocation.

PMID- 16657589
TI  - Cold Acclimation of Hedera helix: Evidence for a Two Phase Process.
AB  - The light-enhanced production and accumulation of sugars is only one step in the
      process of cold acclimation in Hedera helix L. var. Thorndale (English ivy).
      Applications of 2,4-dinitrophenol to plants with different portions exposed to
      light and dark indicated that the mere presence or accumulation of the light
      generated promoters did not invoke an increase in hardiness. Kinetics of cold
      acclimation during alternating periods of light and dark also indicate that the
      light stimulation of cold acclimation is only a partial component of the total
      process. Incubation on 50 mm solutions of sucrose can replace the light
      requirement. A second phase which can proceed in the dark is thought to result in
      the production of proteins which, due to an altered composition or configuration,
      have a greater capacity to bind sugars. This is evidenced by the fact that
      protein from cold acclimated tissue exhibited a higher sugar-binding capacity
      than protein from nonacclimated tissue. Furthermore, the two phases can proceed
      independently of each other, but only upon complementation of the products of the
      two phases is an increase in cold hardiness manifested.

PMID- 16657590
TI  - Cytokinin-controlled Indoleacetic Acid Oxidase Isoenzymes in Tobacco Callus
      Cultures.
AB  - Indoleacetic acid oxidase in tobacco callus tissues (Nicotiana tabacum L.,
      cultivar White Gold) was resolved into seven anionic isoenzymes by polyacrylamide
      gel disc electrophoresis. Different concentrations of kinetin and zeatin in the
      presence of indoleacetic acid affected the level of this enzyme, particularly two
      fast-moving isoenzymes, A(5) and A(6). The optimal concentration of kinetin was
      0.2 mum; increasing concentrations above this level progressively lowered the
      total activity of indoleacetic acid oxidase and repressed the development of
      isoenzymes A(5) and A(6). Actinomycin D and cycloheximide inhibited the
      development of these two isoenzymes under the influence of 0.2 mum kinetin,
      suggesting a requirement for RNA and protein synthesis. The cytokinin-promoted
      indoleacetic acid oxidase isoenzymes A(5) and A(6) increased with time and
      paralleled the dry weight increase of tobacco callus tissues, but the total
      activity of indoleacetic acid oxidase per unit dry weight of tobacco callus
      varied with time depending on the stage of plant growth.

PMID- 16657591
TI  - Water Content and Phytochrome-induced Potential Germination Responses in Lettuce
      Seeds.
AB  - Grand Rapids lettuce seeds (Lactuca sativa L.) with 6 to 8% water content show no
      light-induced germination responses, whereas in seeds with 15% or more water
      content, germination is promoted or retarded by red and far red light
      respectively. By adjusting seed water content, persistent potentiated responses
      to light are induced in the seeds at seed water levels much below that required
      for germination itself. Alternate moistening and drying of seeds in conjunction
      with red and far red irradiations show that potentiated responses may be
      phototransformed only with sufficient seed water. However, the process of drying
      and remoistening has no effect on potentiated responses.

PMID- 16657592
TI  - Nitrate and Nitrite Reduction by Wolffia arrhiza.
AB  - Nitrate reductase was not found to be present in or associated with partially
      purified, intact chloroplasts aqueously isolated from Wolffia arrhiza. Such
      chloroplasts are capable of using nitrite but not nitrate as an electron acceptor
      during light-stimulated electron transport in the absence of additional
      cytoplasmic components. When nitrite acts as an electron acceptor under these
      conditions, on the average 1.5 moles of oxygen are evolved per mole of nitrite
      reduced by the chloroplasts, indicating a probable reduction of nitrite to
      ammonia. Chloroplasts ruptured by osmotic shock fail to reduce nitrite in the
      absence of additional components.

PMID- 16657593
TI  - The plasma membrane of Avena coleoptile protoplasts.
AB  - Treatment of living protoplasts from the Avena coleoptile with enzymes and
      chemicals has provided new information about the external surface of the plasma
      membrane. Treatments with selected detergents and polyene antibiotics indicate
      that little sterol is present. The lysis of protoplasts in carboxymethyl-RNase
      which is enzymatically almost inactive provides strong evidence that the lysis
      previously observed in RNase is not an indication of RNA in the membrane.
      Divalent cations inhibit the RNase-induced lysis, indicating that such lysis
      involves the interaction of RNase with negatively charged sites on the plasma
      membrane surface. Tyrosinase treatment gives no lysis, showing that tyrosine does
      not play the role in these plasma membranes attributed to it in some animal
      cells. Peroxidase does not harm coleoptile protoplasts.

PMID- 16657594
TI  - Developmental changes in ribosomal ribonucleic Acid and fraction I protein in
      wheat leaves.
AB  - In light-grown wheat (Triticum aestivum L.) seedlings, the amount of chloroplast
      and cytoplasmic ribosomal RNA increased to a maximum in the first leaf near the
      end of its growth and declined by about 60% in the following 3 days. While total
      ribosomal RNA was declining, labeled uracil was still incorporated into
      cytoplasmic ribosomal RNA, but the rate of incorporation into chloroplast
      ribosomal RNA fell by more than 80%, as did the incorporation of labeled leucine
      into fraction I protein. Either there is greater replacement of cytoplasmic
      ribosomal RNA than chloroplast ribosomal RNA in mature leaves, or chloroplasts
      are able to repress the incorporation of exogenous precursor when there is no net
      synthesis of RNA.

PMID- 16657595
TI  - Photosynthetic CO(2) Fixation Products and Activities of Enzymes Related to
      Photosynthesis in Bermudagrass and Other Plants.
AB  - After a 5-second exposure of illuminated bermudagrass (Cynodon dactylon L. var.
      ;Coastal') leaves to (14)CO(2), 84% of the incorporated (14)C was recovered as
      aspartate and malate. After transfer from (14)CO(2)-air to (12)CO(2)-air under
      continuous illumination, total radioactivity decreased in aspartate, increased in
      3-phosphoglyceric acid and alanine, and remained relatively constant in malate.
      Carbon atom 1 of alanine was labeled predominantly, which was interpreted to
      indicate that alanine was derived from 3-phosphoglyceric acid. The activity of
      phosphoenolpyruvate carboxylase, alkaline pyrophosphatase, adenylate kinase,
      pyruvate-phosphate dikinase, and malic enzyme in bermudagrass leaf extracts was
      distinctly higher than those in fescue (Festuca arundinacea Schreb.), a reductive
      pentose phosphate cycle plant. Assays of malic enzyme activity indicated that the
      decarboxylation of malate was favored. Both malic enzyme and NADP(+)-specific
      malic dehydrogenase activity were low in bermudagrass compared to sugarcane
      (Saccharum officinarum L.). The activities of NAD(+)-specific malic dehydrogenase
      and acidic pyrophosphatase in leaf extracts were similar among the plant species
      examined, irrespective of the predominant cycle of photosynthesis. Ribulose-1, 5
      diphosphate carboxylase in C(4)-dicarboxylic acid cycle plant leaf extracts was
      about 60%, on a chlorophyll basis, of that in reductive pentose phosphate cycle
      plants.We conclude from the enzyme and (14)C-labeling studies that bermudagrass
      contains the C(4)-dicarboxylic acid cycle and that pyruvate-phosphate dikinase
      does not exist exclusively in C(4)-dicarboxylic acid cycle plants, and we propose
      that in C(4)-dicarboxylic acid cycle plants the transfer of carbon from a
      dicarboxylic acid to 3-phosphoglyceric acid involves a decarboxylation reaction
      and then a refixation of carbon dioxide by ribulose-1, 5-diphosphate carboxylase.

PMID- 16657596
TI  - Relationship of Electrical Conductance at Two Frequencies to Cold Injury and
      Acclimation in Cornus stolonifera Michx.
AB  - The ratio of electrical conductance measured at two frequencies can be used to
      predict the cold hardiness of stem sections of Cornus stolonifera Michx. during
      the first stage of cold acclimation. Electrical conductance at 50 hertz divided
      by electrical conductance at 100 kilohertz gave a better estimate of hardiness
      than measurements at either frequency alone. The observed increase in the
      electrical conductance ratio as hardiness increased is consistent with an
      increase in membrane permeability. After plants were exposed to nonlethal frost,
      hardiness increased rapidly, and the relation between the conductance ratio and
      hardiness changed. This change indicates that ice crystallization induces a
      significant physiological alteration in the plants. Contrary to expectations,
      stem sections exposed to lethal temperatures could not consistently be separated
      from sections exposed to nonlethal temperatures by electrical conductance ratio
      measurements made immediately after thawing.

PMID- 16657597
TI  - An Ontogenetic Study of Canavanine Formation in the Fruit of Jack Bean, Canavalia
      ensiformis (L.) DC.
AB  - An ontogenetic study of canavanine formation in the fruit of jack bean, Canavalia
      ensiformis (L.) DC. was conducted. Evidence was presented to show that the ovary
      wall is the reservoir for seed canavanine. The testa possesses sufficient
      canavanine to account for the continued elevation in seed canavanine after the
      pod senesces. The seed canavanine concentration is not constant inasmuch as the
      canavanine content per milligram dry weight or soluble protein increases abruptly
      with seed growth and levels off only with the onset of fruit ripening.

PMID- 16657598
TI  - Translocation and Metabolic Conversion of C-Labeled Assimilates in Detached and
      Attached Leaves of Phaseolus vulgaris L. in Different Phases of Leaf Expansion.
AB  - Leaf excision greatly affected the actual levels of (14)C-assimilates in laminas
      and petioles of primary bean leaves (Phaseolus vulgaris L.) following a transport
      period. However, it did not affect the percentage of starch in the insoluble
      residue; starch decreased from 20% of the insoluble residue after exposure to
      (14)CO(2) to 3% after 5 hr in both attached and detached leaves. The transition
      from import to export of attached and detached leaves was at the same stage,
      i.e., when the cotyledons were 63 to 85% depleted. The composition of the (14)C
      assimilates in importing leaves was different from that in exporting leaves. In
      the former, only 5% of the soluble label was free sugar, while 74% was free sugar
      in the latter. The failure of importing leaves to export was not due to the
      labeled substances being nontransferable. Extracts from importing leaves applied
      to exporting leaves were exported; these extracts were high in amino acids and
      organic acids but low in free sugar. However, exporting leaves exposed to
      (14)CO(2) appeared to export sugars more readily than amino acids. Cotyledon
      excision did not delay transition of leaves from import to export. Actually,
      excision seemed to enhance slightly the transition of the primary leaves from
      import to export.

PMID- 16657599
TI  - Isolation of Intact Chloroplasts from Euglena gracilis by Zonal Centrifugation.
AB  - Chloroplasts were separated from Euglena gracilis by zonal centrifugation at low
      speed in density gradients of Ficoll or dextran. The chloroplasts were intact by
      the criteria of ultrastructure and their content of ribulose diphosphate
      carboxylase and soluble protein. The chloroplasts also contained ribosomes and
      ribosomal RNA uncontaminated by the corresponding cytoplasmic particles.

PMID- 16657600
TI  - Enhancement models at high light intensities.
AB  - The separate package and spillover models of photosynthetic enhancement are
      generalized and extended to light saturation assuming hyperbolic or exponential
      rate versus intensity curves. The available data are more consistent with the
      exponential model at high light intensities. Two significant conclusions follow:
      (a) the decreases in enhancement observed at high light intensities are accounted
      for by the curvatures of the light intensity curves for photosynthesis, and (b)
      nonlinearity of rate versus intensity curves may be sufficient to reduce
      enhancement greatly even when the intensity curves appear linear.

PMID- 16657601
TI  - Effects of Flashes of Red or Blue Light on the Composition of Starved Chlorella
      pyrenoidosa.
AB  - Autotrophically grown cells of Chlorella pyrenoidosa (211-8b) were starved 3 to 4
      days in darkness, flashes of blue light, or flashes of red light. The blue
      flashes were sufficient to maintain the maximal rate of light-stimulated oxygen
      uptake during short term experiments. However, after 24 hours, the respiration
      rate in red flashes was equal to, or greater than, the rate in blue flashes.
      Starvation in darkness reduced the chlorophyll content by 11%, altered the blue
      absorbance of the nonsaponifiable material only 1 to 2%, and reduced the dry
      weight by 13%. Starvation in the presence of blue or red flashes reduced the dry
      weight by an additional 11 or 12% respectively. Protein per unit cell volume was
      not changed significantly during 3 to 4 days starvation in darkness or in blue
      flashes, even though dry weight per unit cell volume decreased 13% in darkness
      and 23% in blue flashes. In contrast, cells starved under red flashes showed a
      20% decrease in protein per unit cell volume and a 24% decrease in dry weight per
      unit cell volume.

PMID- 16657602
TI  - Chlorophyll synthesis in chlorella: regulation by degree of light limitation of
      growth.
AB  - The degree of light limitation of growth is the primary controlling factor of
      chlorophyll synthesis during photoautotrophic growth of Chlorella. The
      chlorophyll content of the cells increases when light is limiting for growth as
      occurs in dense cultures, or in cultures under low incident light, or when the
      light is used less efficiently through partial inhibition of photosynthesis by 3
      (p-chlorophenyl)-1, 1-dimethylurea. The chlorophyll content decreases when light
      is not limiting for growth, as occurs in cells in high light intensity and in
      dilute suspensions. The initial lag in rate of chlorophyll synthesis in a freshly
      inoculated culture can be attributed to light at first not being growth limiting,
      and then becoming growth limiting as the cell suspension becomes denser.
      Continuous culture experiments support the above conclusions by showing that
      under steady state conditions the chlorophyll content is inversely related to the
      relative available light.

PMID- 16657603
TI  - Cyanide-insensitive Respiration in Plant Mitochondria.
AB  - Pathways of electron transport have been studied in mitochondria isolated from
      hypocotyls of etiolated mung bean seedlings and skunk cabbage spadices that show
      cyanide-resistant respiratory activity. The residual flux through cytochrome c
      oxidase is shown to be small in comparison with the flux through an unidentified
      alternative oxidase that is known to have a high affinity for oxygen. This
      alternative oxidase is not a cytochrome. Skunk cabbage and mung bean mitochondria
      contain cytochromes a and a(3) that have absorption peaks differing slightly from
      those of animal preparations. A slow oxidation-reduction of cytochrome a(3)-CN
      has been demonstrated. Cytochromes b undergo oxidation and reduction in the
      presence of cyanide but play no essential role in the cyanide-resistant pathway.
      Antimycin inhibits to an extent similar to that of cyanide; the respiratory chain
      bifurcates on the substrate side of the antimycin-sensitive site. Evidence is
      presented for the selective inhibition by thiocyanate, alpha, alpha'-dipyridyl,
      and 8-hydroxyquinoline of the alternative oxidase pathway, which may therefore
      contain a non-heme iron protein.

PMID- 16657604
TI  - Uricase and allantoinase in glyoxysomes.
AB  - In fat-degrading tissues of seedlings of seven different plant species examined,
      uricase activity (urate:O(2) oxidoreductase, EC 1.7.33) was associated with
      particulate fractions. After equilibrium density centrifugation on sucrose
      density gradients the enzyme activity was recovered in the glyoxysomal band
      (density: 1.25 grams per cubic centimeter). Allantoinase is also present in
      glyoxysomes but, equally, in the proplastid region (density: 1.22 grams per cubic
      centimeter). Xanthine oxidase, xanthine dehydrogenase, allantoicase, and urease
      were not detected in glyoxysomes from castor bean endosperm. Uricase in these
      particles shows its maximal activity at pH 8.9. The apparent K(m) is 7.4 mum.
      Urate concentrations greater than 120 mum as well as certain other purine
      compounds inhibit the enzyme. Cyanide at a concentration of 10 mum is a potent
      inhibitor. 2,6-Dichlorophenolindophenol did not substitute for oxygen as electron
      acceptor.

PMID- 16657605
TI  - Formation of chlorophyll B, and the fluorescence properties and photochemical
      activities of isolated plastids from greening pea seedlings.
AB  - Chlorophyll b was first detectable after 10 minutes of illumination of etiolated
      pea seedlings (Pisum sativum L. var Greenfeast) with continuous white light. The
      chlorophyll a/b ratio decreased from 300 at 10 minutes to 15 after 1 hour. There
      was little change in the chlorophyll a/b ratio between 1 and 2 hours, and it
      declined to 3 between 2 and 5 hours of illumination. In red light, the time
      courses of total chlorophyll synthesis and chlorophyll a/b ratio were similar to
      those in white light for the first 5 hours of illumination. But with increasing
      time of illumination with red light, there was an increase in the chlorophyll a/b
      ratio to 7 after 30 hours. Illumination with white light of very low intensity
      also gave high chlorophyll a/b ratios. Seedlings which had been illuminated for
      varying periods and then returned to darkness always showed an increase in
      chlorophyll a/b ratio during the dark period. It is concluded that the synthesis
      of chlorophyll b is controlled by light.The onset of the transfer of excitation
      energy from carotenoids to chlorophyll a correlated with the appearance of
      chlorophyll b. The detection of chlorophyll b and the onset of energy transfer
      from carotenoids to chlorophyll a preceded by several hours the appearance of
      Hill activity in the isolated pea plastids. The detection of the large
      fluorescence emission band at 735 nm at 77 K also preceded the observation of
      Hill activity, but it correlated with the phase of rapid chlorophyll synthesis.
      There was a good correlation between Hill activity and the formation of grana.
      The fluorescence kinetics which are characteristic of mature chloroplasts
      appeared considerably later than grana or the observation of Hill activity.It is
      concluded that the formation of photosynthetic membranes and the assembly of the
      photosystems is not a single step process, at least in the initial stages of
      chloroplast development from the etioplast.

PMID- 16657606
TI  - Chromatin- and nuclei-directed ribonucleic Acid synthesis in sugar beet root.
AB  - The synthesis of RNA by chromatin-bound RNA polymerase prepared from sugar beet
      (Beta vulgaris) root tissue is completely dependent on the presence of a divalent
      metal (Mg(2+) or Mn(2+)) and the presence of four ribonucleoside triphosphates.
      Accumulation of labeled acid-insoluble product is inhibited by the addition of
      RNase and actinomycin D to the reaction. When beet root slices are washed for 25
      hours, chromatin-associated RNA polymerase activity increases 7-fold over that of
      unwashed tissue. This enzyme activity declines with further washing. DNA template
      availability, as measured by saturating levels of added Escherichia coli RNA
      polymerase, was also found to follow a pattern similar to that for RNA
      polymerase. Nearest neighbor frequencies of the RNA synthesized by chromatin
      isolated from unwashed and washed tissue are different.Washing tissue in
      solutions of gibberellic acid and auxin enhances template availability of the
      isolated chromatin. Experiments with isolated nuclei indicate an effect of these
      hormones on RNA synthesis.

PMID- 16657607
TI  - Effect of Errors in Measuring Leaf Temperature and Ambient Gas Concentration on
      Calculated Resistances to CO(2) and Water Vapor Exchanges in Plant Leaves.
AB  - Errors as small as 1 C in the measurement of leaf temperature (T(leaf)) are shown
      to cause significant changes in the estimated value of the stomatal resistance
      (expressed in terms of total resistance to water vapor transfer, summation
      operatorrH(2)O). The effect increases as T(leaf) increases and as ambient
      relative humidity increases, if other conditions are maintained constant. The
      effect on the key CO(2) exchange parameter, the intracellular (or mesophyll)
      resistance, r(int), tends to be small under open stomata conditions but increases
      rapidly as stomatal closure occurs, particularly if the true value of r(int) is
      relatively small.Errors in the determination of the ambient water vapor and CO(2)
      concentrations can also significantly affect the calculated value of summation
      operatorrH(2)O and r(int). The effect on summation operatorrH(2)O and summation
      operatorrCO(2) increases as the ratio of the inlet/outlet concentration departs
      from unity and also increases as the assumed leaf-air concentration difference
      decreases. The combined effect on r(int) tends to be less than the individual
      effects on summation operatorrH(2)O and summation operatorrCO(2) since both are
      in the same direction.

PMID- 16657608
TI  - The metabolism and biological activity of a 9-substituted cytokinin.
AB  - In order to test the metabolic stability of 9-substituted cytokinins, 6
      benzylamino-9-methyl purine has been synthesized and labeled with (14)C in the 9
      methyl carbon or doubly labeled with (14)C in the 9-methyl carbon and (3)H in the
      methylene moiety of the side chain. Although the 6-benzylamino-9-methylpurine is
      chemically stable, cytokinin-requiring tissues begin removing the 9-substituent
      in as little as 10 minutes. Among the various metabolic products is free
      benzylaminopurine. Thus, the biological activity of 9-substituted cytokinins
      could be accounted for by their conversion to the free base.

PMID- 16657609
TI  - The Respiratory Chain of Plant Mitochondria: IX. Oxidation-Reduction Potentials
      of the Cytochromes of Mung Bean Mitochondria.
AB  - The oxidation-reduction potentials of the cytochromes of the respiratory chain of
      mung bean (Phaseolus aureus) mitochondria have been measured under strictly
      anaerobic conditions with a combined spectrophotometric/potentiometric method.
      The midpoint potentials at pH 7.2 are as follows: cytochrome a: +190 millivolts;
      a(3): +380 millivolts; b(553): +75 millivolts; b(557): +42 millivolts; b(562): 
      77 millivolts; c(547) and c(549): +235 millivolts. (The subscripts refer to the
      difference absorbance maxima observed for these cytochromes in reduced-minus
      oxidized difference spectra recorded at 77 K.) The same values of midpoint
      potentials at pH 7.2 are obtained with mitochondria depleted of energy by aerobic
      incubation with ADP and uncoupler in the presence of inorganic phosphate, or with
      coupled mitochondria energized with ATP in the absence of inorganic phosphate.
      Coupling site II is placed between b(553)/b(557) and c(549)/c(547) in these
      mitochondria, and coupling site III is placed between a and a(3).

PMID- 16657610
TI  - The Nature of Cold-induced Dormancy in Urediospores of Puccinia graminis tritici.
AB  - When air-dry urediospores of the wheat stem rust, Puccinia graminis f. sp.
      tritici, are exposed to temperatures below freezing, their germinability is
      markedly reduced, even after prolonged thawing at room temperature. Germinability
      is fully restored by a brief heat-shock or by vapor phase hydration. We have
      found that this "cold dormancy" cannot be reversed once the spores contact liquid
      water. Enhanced loss of metabolites occurs immediately upon suspension of cold
      dormant urediospores in liquid without a prior heat-shock. Such leakage is two to
      three times greater than from untreated or heatshocked cold-dormant spores and
      accounts for up to 70% of the soluble pool of metabolites normally present in
      germinating urediospores. Respiratory activity of cold-dormant urediospores
      declines rapidly during incubation in liquid. Incorporation of isotopic carbon
      into cold-dormant urediospores is only a fraction of that of untreated or heat
      activated spores. Thus, cold shock transforms the spores into a state of
      supersensitivity to liquid water, which is reversed by heat-shock or slow
      hydration by vapor phase equilibration. The primary cause of damage to cold
      dormant cells exposed to liquid water appears to be irreversible permeability
      damage, followed by metabolic injury.

PMID- 16657611
TI  - Studies of sulfate utilization by algae: 8. The ubiquity of sulfate reduction to
      thiosulfate.
AB  - Cell-free extracts from several microorganisms, when prepared by methods
      originally devised for Chlorella pyrenoidosa (Emerson strain 3) and incubated
      anaerobically with ATP, Mg(2+), and 2, 3-dimercaptopropan-1-ol, are capable of
      reducing sulfate-(35)S to thiosulfate. These microorganisms include, in addition
      to C. pyrenoidosa (Emerson strain 3), several other strains of C. pyrenoidosa,
      Chlorella protothecoides, Chlorella vulgaris, Anacystis sp., Chlamydomonas
      reinhardi, Escherichia coli, Salmonella typhimurium, and baker's yeast. Three of
      these organisms, E. coli, S. typhimurium, and baker's yeast, were previously
      reported by others to reduce sulfate to sulfite. Moreover, three mutant strains
      of S. typhimurium (Ba-25, Ce-363, and Bc-482) previously reported by other
      workers to be unable to reduce sulfate to sulfite also cannot form thiosulfate,
      and one mutant strain (Cd-68) reportedly able to form sulfite can also form
      thiosulfate. Taken together, this suggests that thiosulfate-forming activity may
      be a common feature of sulfate-reducing systems, and it may be present in
      enzymatic systems previously thought to be forming sulfite. Reasonably conclusive
      identification of thiosulfate is provided by ion exchange chromatography and by
      paper electrophoresis; the ambiguities associated with other analytical methods
      are discussed.

PMID- 16657612
TI  - Studies of Sulfate Utilization by Algae: 9. Fractionation of a Cell-free System
      from Chlorella into Two Activities Necessary for the Reduction of Adenosine 3'
      Phosphate 5'-Phosphosulfate to Acid-Volatile Radioactivity.
AB  - Further properties of the enzymatic system obtained from Chlorella pyrenoidosa
      (Emerson strain 3) which reduces adenosine 3'-phosphate 5'-phosphosulfate-(35)S
      to acid-volatile radioactivity, when fortified with Mg(2+) and 2, 3
      dimercaptopropan-1-ol as reductant, are described. Optimal concentrations of
      adenosine 3'-phosphate 5'-phosphosulfate-(35)S and Mg(2+) and the pH optimum have
      been determined. 2,3-Dimercaptopropan-1-ol can be replaced by dithiothreitol,
      mercaptoethanol, reduced glutathione, cysteine, and cysteamine. Treatment of the
      crude extracts with ammonium sulfate and alumina C-gamma gel yields two
      fractions, designated "S" and "A," which must be recombined to obtain acid
      volatile radioactivity. Further fractionation of fraction S by ammonium sulfate
      gradient elution and diethylaminoethyl cellulose chromatography yields
      approximately a 50-fold increase in specific activity compared to that found in
      the crude extract. This material appears to contain an active component with a
      molecular weight estimated by agarose gel chromatography of about 330,000.

PMID- 16657613
TI  - Studies of sulfate utilization by algae: 10. Nutritional and enzymatic
      characterization of chlorella mutants impaired for sulfate utilization.
AB  - Seven mutants of Chlorella pyrenoidosa (Emerson strain 3) impaired for sulfate
      utilization have been isolated after treatment of the wild-type organism with
      nitrosoguanidine by replica plating on media containing thiosulfate and l
      methionine. These mutants fall into three classes based on their ability to grow
      on sulfate, accumulate compounds labeled from sulfate-(35)S, and reduce adenosine
      3'-phosphate 5'-phosphosulfate-(35)S (PAPS-(35)S) to thiosulfate-(35)S. Mutant
      Sat(2) (-) cannot grow on sulfate, but it accumulates thiosulfate-(35)S and
      homocysteic acid-(35)S from sulfate-(35)S in vivo. In addition, extracts of
      mutant Sat(2) (-) reduce PAPS-(35)S to thiosulfate-(35)S, indicating the
      possession of enzyme fractions S and A, both of which are required for
      thiosulfate formation. Mutants Sat(1) (-), Sat(3) (-), Sat(4) (-), Sat(5) (-),
      and Sat(6) (-) cannot grow on sulfate, and their extracts lack the ability to
      reduce PAPS-(35)S to thiosulfate-(35)S. Mutant Sat(7) (-)R(1), a probable
      revertant, can grow on sulfate but still lacks the ability to reduce PAPS-(35)S
      to thiosulfate-(35)S in vitro. Complementation experiments in vitro show that the
      block in formation of acid-volatile radioactivity in every case is due to the
      absence of activity associated with fraction S. All mutants can grow on
      thiosulfate and all possess the activating enzymes which convert sulfate to PAPS.
      Through a comparison of nutritional and enzymatic characteristics, the first
      outlines of a branched and complicated pathway for sulfate reduction in Chlorella
      are beginning to emerge.

PMID- 16657614
TI  - Effects of Seselin and Coumarin on Growth, Indoleacetic Acid Oxidase, and
      Peroxidase, with Special Reference to Cucumber (Cucumis sativa L.) Radicles.
AB  - Seselin, a natural coumarin derivative isolated from citrus roots, inhibited
      radicle growth in seedlings of cucumber (Cucumis sativa), lettuce (Lactuca
      sativum), radish (Raphanus sativus), and wheat (Triticum aestivum) grown in the
      dark. Coumarin similarly inhibited radicle growth of cucumber seedlings. Growth
      retardation of the cucumber radicles was accompanied by an increased activity of
      peroxidase and indole-3-acetic acid oxidase. Both compounds antagonized indole-3
      acetic acid-induced growth of wheat coleoptiles, whereas coumarin was much less
      effective than seselin in antagonizing gibberellic acid-induced release of
      reducing sugars from barley endosperm. It is suggested that seselin plays an
      important role in the regulation of root growth, and that it is the indole-3
      acetic acid oxidase cofactor previously detected in citrus roots.

PMID- 16657615
TI  - Ribosomes and Polysomes in Cucumber Leaves during Growth and Senescence.
AB  - The quantity of RNA in the ribosomal fraction of the first leaf of cucumber
      (Cucumis sativus) increases during growth, reaches a maximum before the final
      fresh weight is attained, and then decreases. The main changes are in the free
      ribosome fraction, the quantity of membrane-bound ribosomes remaining about
      constant. Few 65.5S chloroplast ribosomes are present in small leaves; however,
      they increase in quantity rapidly during growth and form about half of the
      ribosomes present in the mature fully green leaf. The cytoplasmic ribosomes have
      a sedimentation coefficient of 77.6S. Ribonuclease-sensitive polysomes were
      present in leaves of all ages except possibly the very oldest. The proportion of
      ribosomes in polysome form decreases during growth and then remains roughly
      constant during senescence. Following maturation of the leaf, the rate of
      incorporation of (32)P into ribosomal-fraction RNA begins to decline. This
      decline could account for the loss of ribosomes during the early stages of
      senescence. The possibility that leaf ribonuclease might be responsible for the
      final, more rapid loss of RNA, is discussed.

PMID- 16657616
TI  - Translocation of carbon in powdery mildewed barley.
AB  - This paper compares translocation in healthy and powdery mildew (Erysiphe
      graminis f. sp. hordei, race CR3) infected barley (Hordeum vulgare, variety
      Manchuria). The sink-like properties of the powdery mildew infection were used to
      determine what effect imposing a sink in the midst of normal source tissue
      (mature primary leaf) had on the translocation process. The pattern of
      translocation was determined by monitoring the movement of (14)C which was
      photosynthetically incorporated from (14)C either by the primary or second leaf.
      In the healthy primary leaf of barley, (14)C fixed in the tip section of the
      blade was preferentially translocated to the root, whereas (14)C fixed in the
      basal section was primarily translocated to the shoot. When a sporulating powdery
      mildew infection was present in the mid-section of the primary leaf, (14)C fixed
      in that section or in the acropetal healthy tip section readily accumulated in
      the infection area. Labeled carbon fixed in the healthy basal section was
      translocated into the other parts of the plant with only a small fraction moving
      acropetally into the infected mid-section. The (14)C fixed by the second leaf was
      translocated to the root and younger shoot with very little entering the primary
      leaf. The presence of the mildew infection did not alter this pattern.

PMID- 16657617
TI  - Changes in Lipid Composition during Greening of Etiolated Pea Seedlings.
AB  - After 7 days of germination in the dark, the three sections of pea seedlings
      studied (cotyledons, stems, and young leaves) are rich in linoleic acid; after
      illumination of the seedlings a very significant increase in linolenic acid is
      observed in the young leaves section, whereas only small variations are noted in
      the fatty acid composition of the other sections. The increase in linolenic acid
      results from the increase in galactolipid content of the young leaves; these
      already linolenic acid-rich galactolipids are present but only in small amounts
      in the etiolated seedlings (10% of total lipid).Variations in composition of the
      other lipid classes (phospholipids and neutral fats) were also studied. The
      possibility of fatty acid transport from the cotyledons toward the young leaves
      during the synthesis of the photosynthetic apparatus is discussed.

PMID- 16657618
TI  - Induction of coleoptile elongation by carbon dioxide.
AB  - The ability of CO(2) to induce elongation of Avena sativa coleoptile segments was
      examined with the use of a high resolution growth-recording device. CO(2)
      saturated water causes an 8- to 16-fold promotion in the rate of elongation
      within 1 minute. This elongation is insensitive to a variety of metabolic
      inhibitors that suppress auxin-induced elongation, and the CO(2) effect cannot be
      prevented by pretreatment with these inhibitors. Buffers of pH 3 to 4 also
      stimulate elongation quickly, and it seems that at least a major part of the
      action of CO(2) depends upon its ability to reduce pH. The rate of elongation of
      auxin-promoted segments can be further enhanced by treatment with CO(2) but not
      vice versa.The response to CO(2) can be inhibited by mannitol at osmotic
      concentrations that inhibit normal growth, by calcium, and by brief pretreatment
      with heavy water (D(2)O). The elongation rate that results from CO(2) treatment
      is sensitive to temperature, but the induction by CO(2) itself appears to be
      almost temperature-independent.Elongation following treatment with CO(2) may be a
      physical flow phenomenon, essentially independent of immediate biochemical
      participation, which occurs when wall polymer interactions that normally restrict
      strain in the cell wall are weakened or broken by CO(2) in a manner that in
      effect substitutes for the role of metabolism in normal auxin-inducible cell
      enlargement.

PMID- 16657619
TI  - Electrophoretic Analysis of Histones from Gibberellic Acid-treated Dwarf Peas.
AB  - Histones from the epicotyls of light-grown dwarf peas (Pisum sativum L. cv.
      Little Marvel) which had been treated with gibberellic acid were compared to
      histones from control dwarf peas by the method of polyacrylamide gel
      electrophoresis. The histone complements were found to be unaltered in the
      electrophoretic mobility and relative quantity of the individual fractions. The
      ratio of histone to DNA was also unaffected by treatment with gibberellic acid.
      The investigation confirmed earlier reports that over 95% of the histone of peas
      is contained in seven molecular species and that one of these can exist both as
      an oxidized disulfide dimer and as a reduced monomer. Evidence is presented which
      indicates that only the monomer form exists in vivo in the pea epicotyl tissue
      and that the oxidized dimer is an artifact of extraction. The implications of the
      data concerning the mechanism of action of gibberellic acid are discussed.

PMID- 16657620
TI  - Specificity of deoxyribonucleic Acid intercalating compounds in the control of
      phenylalanine ammonia lyase and pisatin levels.
AB  - Compounds with planar triple ring systems such as acridine orange, 9-amino
      acridine, 9-amino-1,2,3,4-tetrahydroacridine (tacrine), 6,9-diamino-2
      ethoxyacridine lactate monohydrate (DE-acridine), 6-chloro-9-(3'-diethylamino-2'
      hydroxypropylamino) -2-methoxyacridine.2 HCl (CDM-acridine), quinacrine, 6-chloro
      9-(4'-diethylamino-1'-methylbutylamino) -2-methoxy-1,10-diazaanthracene (CDM 1,10
      diazaanthracene), thionine, azure A, methylene blue, and pyronine Y when applied
      to excised pea pods were potent inducers of phenylalanine ammonia lyase or of
      pisatin, or of both. Compounds with an array of structural variation around the
      planar three-ring system were tested for their ability to induce these responses
      in pea tissue. In general, dimethylamino, diethylamino, or amino substitutions at
      position 2 and 6 or an amino (with or without an aliphatic side chain)
      substitution at position 9 of the three-ring system augmented induction
      potential. Methyl green, methylene blue, 2,7-diaminofluorene, nile blue, neutral
      red, pyrogallol red, ethidium bromide, nogalamycin, quinine, chloroquine,
      spermine, 8-azaguanine, gliotoxin, chromomycin A(3), actinomycin D, and mitomycin
      C were also potent inducers. The inhibition of phenylalanine ammonia lyase
      induction by the application of actinomycin D (300 micrograms per milliliter) or
      6-methylpurine (1 milligram per milliliter) within 1 hour after inducer
      application indicated that newly synthesized RNA is necessary for induction.
      Phenylalanine ammonia lyase induction was also inhibited by cycloheximide (150
      micrograms per milliliter).

PMID- 16657621
TI  - Phytochrome-controlled Leaf Unrolling and Protein Synthesis.
AB  - In the primary leaf sections of etiolated wheat (Triticum aestivum L.) seedlings,
      red light-induced unrolling is accompanied by an increase in incorporation of
      (14)C-leucine into protein. By differential centrifugation, the unrolling
      response was found to be closely related to incorporation of the amino acid into
      the supernatant fraction (105,000g). Cycloheximide and chloramphenicol inhibit
      both leaf unrolling and synthesis of the supernatant protein, although
      chloramphenicol exerts its effect more strongly on the fraction which presumably
      contains the plastids. In a barley (Hordeum vulgare L.) albino mutant completely
      devoid of ribulose diphosphate carboxylase activity, only incorporation of (14)C
      leucine into the supernatant fraction is substantially promoted by red light.
      This mutant exhibits the photoresponse of leaf unrolling.Both unrolling and
      increased incorporation of (14)C-leucine induced by red light are prevented by
      indoleacetic and abscisic acids. Kinetin promotes leucine incorporation into
      protein and can induce unrolling in complete darkness. Protein synthesis is still
      promoted by red light when unrolling is almost completely inhibited by an
      osmoticum. It is suggested that the action of red light on leaf unrolling is
      dependent on synthesis of a soluble protein in the tissue.

PMID- 16657622
TI  - Absorption of magnesium and chloride by excised corn root.
AB  - Absorption characteristics of Mg(2+) and Cl(-) were investigated with 5-day-old
      excised corn (Zea mays) roots. Uptake from both 0.5 and 10 milliequivalents per
      liter MgCl(2) solutions occurred at steady state rates for the first 6 hours.
      Inhibition by dinitrophenol and low temperatures established that absorption
      during this period was metabolically mediated in the absence and presence of
      Ca(2+). Absorption isotherms indicated dual mechanisms of Mg(2+) and Cl(-)
      absorption from solutions above 1 milliequivalent per liter. The effect of H(+)
      on absorption of Mg(2+) and Cl(-) was typical of that generally reported for
      other plant roots and other ions. In the physiological pH range, Ca(2+) greatly
      suppressed the rate of Mg(2+) absorption but had little effect on Cl(-). The
      influence of Ca(2+) on Mg(2+) appeared to be noncompetitive and independent of
      its effect on membrane permeability.

PMID- 16657623
TI  - Method for determining solutes in the cell walls of leaves.
AB  - A perfusion method is described whereby large discs of amphistomatous leaves are
      vacuum-perfused with water so that either successive fractions of perfusate may
      be analyzed for solutes or the infused water may be displaced and collected after
      equilibration with the leaf cells. With castor bean leaves, estimates of
      electrolyte concentration in cell wall water by the two methods were similar.
      Total electrolytes in leaf cell wall water of castor beans (Ricinus communis),
      sunflower (Helianthus annuus), and cabbage (Brassica oleracea capitata) from
      nonsaline cultures were about 2, 2, and 10 milliequivalents per liter,
      respectively, increasing to 4, 10, and 30 milliequivalents per liter under saline
      conditions. Electrolytes recovered in successive fractions were similar in
      composition, and continuous perfusion resulted in a steady release of solutes,
      the concentration in the perfusate varying inversely with the perfusion rate.
      Diffusional release of solutes from cells was less than expected at low perfusion
      rates, suggesting that solute reabsorption may increase as solute concentration
      in the perfusate increases with decreased perfusion rates. Perfusate
      concentration and composition were essentially unaffected by temperature (2 and
      23 C) or by perfusing with 0.5 mm CaSO(4) rather than with water. Electrolytes in
      perfusates on an equivalent basis were Ca(2+), 30%; Mg(2+), 10%; and Na(+) +
      K(+), 60%, the proportions of sodium increasing from 10 to 50% in leaves
      (cabbage) that accumulated sodium under saline conditions. Salinity (added NaCl)
      of the root culture medium caused a 3- to 5-fold increase in total cell wall
      electrolyte concentration, but this amounted to an increase from less than 1 or a
      few per cent to no more than 7% (in cabbage) of the cell sap electrolyte
      concentrations. Solutes in the cell wall appear to be in dynamic equilibrium with
      intracellular solutes.

PMID- 16657624
TI  - Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.).
AB  - Five conspicuous indole derivatives are present in leaves and other tissues of
      woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B,
      glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter
      three indole glucosinolates are present at levels of at least 260, 69, and 200
      milligrams per kilogram fresh weight and were isolated as crystalline salts.
      Comparison of physical and chemical properties, particularly NMR spectral
      analysis, confirms that the 1-methoxyglucobrassicin structure suggested for
      neoglucobrassicin is correct, whereas further evidence for the even more unusual
      sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained.
      Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that
      of glucobrassicin. As it too releases thiocyanate, it must be added to the list
      of known plant goitrogens. These studies and the techniques described establish
      woad as exceptionally suitable higher plant material for metabolic studies of
      indoles related to goitrogens and auxins.

PMID- 16657625
TI  - The Kok Effect in Chlamydomonas reinhardi.
AB  - A Haxo-Blinks rate-measuring oxygen electrode together with a modulated light
      source gave an average current signal (change in net O(2) exchange) and a
      modulated current signal (photosynthetic O(2) evolution). Using this apparatus,
      net O(2) exchange and photosynthetic O(2) evolution at low intensities have been
      studied in the green alga, Chlamydomonas reinhardi. At both 645 nm and 695 nm,
      the curves of net O(2) exchange as a function of light intensity were steeper at
      lowest intensities than about compensation, indicative of the Kok effect. The
      effect was greater at 695 nm than at 645 nm. The corresponding curves of
      photosynthetic O(2) evolution, on the other hand, showed no Kok effect; here, the
      slope was lowest at lowest intensity. The absence of the Kok effect in O(2)
      evolution, together with its sensitivity to monofluoroacetic acid, show that it
      is due to an interaction of photosynthesis and respiration. The effect was
      exaggerated by 3-(3,4-dichlorophenyl)-1,1-dimethylurea. In the presence of
      concentrations of this inhibitor sufficient to inhibit O(2) evolution completely,
      a light-induced change in net O(2) exchange remained. This was interpreted as a
      system I dependent depression of respiratory O(2) uptake. The Kok effect remained
      undiminished in concentrations of carbonyl cyanide m-chlorophenylhydrazone and
      2,4-dinitrophenol which partially uncoupled either oxidative phosphorylation
      alone or both oxidative and photosynthetic phosphorylations. The above results
      can be explained within a model of the Kok effect in which O(2) uptake is
      depressed by diversion of reductant away from respiratory electron transport and
      into photosystem I. The same photodepression of O(2) uptake also appears to
      account for a transient in net O(2) exchange seen in several algae upon turning
      off the light.

PMID- 16657626
TI  - Two categories of c/c ratios for higher plants.
AB  - (13)C/(12)C ratios have been determined for plant tissue from 104 species
      representing 60 families. Higher plants fall into two categories, those with low
      delta(PDBI) (13)C values (-24 to -34 per thousand) and those with high delta
      (13)C values (-6 to -19 per thousand). Algae have delta (13)C values of -12 to 
      23 per thousand. Photosynthetic fractionation leading to such values is
      discussed.

PMID- 16657627
TI  - The Effect of Red Irradiation on Plastid Ribosomal RNA Synthesis in Dark-grown
      Pea Seedlings.
AB  - Dark-grown pea seedlings (Pisum sativum L.) were irradiated for a short period
      each day with low intensity red light (662 nm), red light immediately followed by
      far red light (730 nm), or far red light alone. Other plants were transferred to
      a white light regime (14 hours light/10 hours dark). There was no change in the
      amount of RNA in the tissue on a fresh weight basis after the various treatments.
      However, compared with dark-grown seedlings, those plants irradiated with red
      light showed an increase in the net RNA content per stem apex. In addition there
      was a two- to three-fold increase in ribosomal RNA of the etioplasts relative to
      the total ribosomal RNA. These increases were comparable to those found in plants
      grown in the white light regime. The changes were much smaller if the dark-grown
      plants were irradiated either with red light followed by far red light, or with
      far red light alone. Thus continuous light is not essential for the production of
      ribosomal RNA in plastids, and the levels of ribosomal RNA found in chloroplasts
      can also be attained in etioplasts of pea leaves in the dark provided the leaf
      phytochrome is maintained in its active form.

PMID- 16657628
TI  - Reversibility of chilling injury to corn seedlings.
AB  - Seedlings of corn (Zea mays) were tested for recovery from chilling injury
      incurred at 0.3 +/- 0.3 C. At 0.3 C visual leaf injury appeared in 36 hours,
      whereas stem and root injuries appeared later. Appearance of leaf injury was
      preceded by a rise in O(2) uptake and a lessened effect of 2,4-dinitrophenol on
      O(2) uptake by leaf segments and was accompanied by increased ion leakage from
      the leaves. These effects were reversible, in that transfer of seedlings to 21 C
      after 36 hours at 0.3 C produced a return of O(2) uptake, 2,4-dinitrophenol
      stimulation, and ion leakage to the levels of unchilled leaves, as well as a
      disappearance of leaf symptoms, within 72 hours. For most seedlings, transfer to
      21 C after 48 to 60 hours at 0.3 C reversed the chilling effects on O(2) uptake,
      2,4-dinitrophenol stimulation, and injury symptoms but not on ion leakage within
      108 hours. However, some seedlings collapsed during 48 to 60 hours of chilling,
      and these never recovered. Transfer to 21 C after 72 hours at 0.3 C did not
      produce recovery from any symptom of chilling injury examined, and these
      seedlings soon died. No growth occurred at 0.3 C, but growth began soon after
      transfer to 21 C. Seedlings chilled 24 or 36 hours grew at reduced rates during
      the first 72 hours at 21 C, but within 96 hours at 21 C were growing at the same
      rate as nonchilled seedlings. These results demonstrate considerable capacity of
      growing plants to recover from short chilling treatments even though significant
      physiological changes occurred at low temperatures.

PMID- 16657629
TI  - Photomorphogenesis in Arabidopsis thaliana (L.) Heynh: Threshold Intensities and
      Blue-Far-red Synergism in Floral Induction.
AB  - Arabidopsis seeds were germinated on sterile mineral agar supplemented with 1%
      glucose and cultured under continuous light regimes. With 4-hour incandescent
      plus 20-hour monochromatic illumination in the region from 400 to 485 nanometers
      there was effective floral induction at an intensity of 100 microwatts per square
      centimeter. Exclusion of far red wave lengths from the 4-hour incandescent period
      sharply reduced the effectiveness of subsequent monochromatic blue light in
      promoting floral induction. Delayed floral induction occurred under continuous
      incandescent light lacking far red and was attributable to the blue wave lengths.
      Continuous 485 nanometer (100 microwatts per square centimeter) exposure without
      any white light treatment during the postgermination growth period was
      ineffective in floral induction and meristem development. Light at 730 nanometers
      under the same conditions was partially effective, whereas energy between 500 and
      700 nanometers was completely ineffective. When continuous monochromatic light at
      a 3-fold higher energy level was administered, all photomorphogenic responses
      were accomplished with 485 nanometer light, including germination and 100% floral
      induction without any white light treatment at any time during the experiment.
      Almost equal quantum effectiveness was calculated when equivalent quantum flux
      densities in the region from 710 to 740 nanometers or at 485 nanometers were
      used. It is postulated that floral induction in Arabidopsis may be the result of
      a continuous excitation of a stable form of far red-absorbing phytochrome
      localized in or on a membrane, and that excitation can be either by direct
      absorption of energy by far red-absorbing phytochrome or by transfer from an
      accessory pigment.

PMID- 16657630
TI  - Kinetin inhibition of h-uracil and C-leucine incorporation by tobacco cells in
      suspension culture.
AB  - The rate of (14)C-leucine and (3)H-uracil incorporation by tobacco cells
      (Nicotiana tabaccum var. Samsun N.N.) in suspension culture was simultaneously
      decreased by the addition of kinetin at concentrations above 2.5 x 10(-5)m.
      Ribosomal RNA was the first RNA species affected by kinetin. The purine
      derivatives, adenine and N(6)-methyl-aminopurine, which exhibit low cytokinin
      activity overcame the inhibitory effects of kinetin. However, purine derivatives
      without cytokinin activity, guanine, N(6,6)-dimethyl-aminopurine, and 2
      aminopurine, did not relieve kinetin inhibition.

PMID- 16657631
TI  - Starch metabolism in the leaf sheaths and culm of rice.
AB  - The levels of starch and dextrin, free sugars, soluble protein, and enzymes
      involved in starch metabolism-alpha-amylase, beta-amylase, phosphorylase, Q
      enzyme, R-enzyme, and ADP-glucose starch synthetases-were assayed in the leaf
      sheaths and culm of the rice plant (Oryza sativa L., variety IR8) during
      growth.Starch accumulation in the leaf sheaths reached a maximum 10 to 11 weeks
      after transplanting, the time of development of the rice panicle. Maximal
      concentration of free sugars occurred earlier. Starch and sugars in the leaf
      sheaths and culm decreased rapidly during grain development.During starch
      accumulation, the starch granules of the leaf sheaths increased slightly in size
      and its gelatinization temperature decreased. The molecular size of amylose and
      amylopectin and amylose content of the starch were similar in both culm and leaf
      sheaths.Changes in the level of soluble protein paralleled changes in starch
      level in the leaf sheaths. Among the enzymes, only synthetase bound to the starch
      granule paralleled the level of starch in the leaf sheaths and in the culm. ADP
      glucose, but not UDP-glucose, was utilized as a glucosyl donor by these starch
      synthetases. Zymograms of these extracts showed only one alpha-amylase band, one
      beta-amylase band, two phosphorylase bands, and one Q-enzyme band.

PMID- 16657632
TI  - Nonsynchronized Oscillations in Stomatal Resistance among Sclerophylls of
      Eucalyptus umbra.
AB  - Oscillations in stomatal resistance to viscous air flow have been recorded in the
      juvenile and adult sclerophylls of Eucalyptus umbra R. T. Baker, in both
      controlled and natural environments. Under constant illumination, temperature,
      and humidity, irregular oscillations in stomatal resistance with a periodicity of
      approximately 20 to 30 minutes occurred spontaneously, when the soil water
      potential was approximately -0.2 bar. In the natural summer environment, similar
      stomatal oscillations developed with periods ranging from 60 to 100 minutes only
      after imposition of soil moisture stress equivalent to -2 to -3 bars water
      potential. These cycles in stomatal resistance were not synchronized among the
      leaves of a given plant in any of the experiments.

PMID- 16657633
TI  - Gibberellic Acid-enhanced Release of beta-1,3-Glucanase from Barley Aleurone
      Cells.
AB  - A beta-1, 3-glucanase of barley (Hordeum vulgare) aleurone cells accumulates when
      half-seeds are imbibed on water, and accumulation continues when the aleurone
      layers are incubated in buffer solution. The release of the enzyme is a
      gibberellic acid-dependent process, however. Although gibberellic acid stimulates
      glucanase release, it does not markedly affect the total amount of glucanase
      obtained from these cells when compared with water controls. beta-1, 3-Glucanase
      release from aleurone cells is a function of gibberellic acid concentration and
      commences after a 4-hour lag period. Processes occurring during this lag period
      are also dependent upon gibberellic acid concentration. Removal of gibberellic
      acid from the incubation medium at the end of the lag period, however, does not
      affect subsequent release of glucanase. The release of glucanase from aleurone
      cells is an active process with a Q(10) greater than 3. Inhibitors of respiration
      and protein and RNA synthesis effectively inhibit the formation and release of
      glucanase. It is concluded that gibberellic acid functions primarily to enhance
      glucanase release rather than its formation.

PMID- 16657634
TI  - The regulation of cambial division and secondary xylem differentiation in
      xanthium by auxins and gibberellin.
AB  - Cambial division continued in decapitated Xanthium plants without concomitant
      xylem fiber differentiation. The application of indoleacetic acid to these plants
      did not affect the production of cambial derivatives or induce xylem fiber
      differentiation. When naphthaleneacetic acid was applied either to the second
      internode or to the stump of a lateral shoot, xylem fiber differentiation was
      induced in the newly formed cambial derivatives on the xylem side of the cambium
      in the stem. When naphthaleneacetic acid was applied unilaterally, xylem fiber
      differentiation was restricted to that side of the stem in the first internode
      and hypocotyl. Naphthaleneacetic acid also enhanced the production of cambial
      derivatives. Gibberellic acid enhanced cambial derivative production but did not
      affect the differentiation of xylem fibers. Similar numbers of cambial
      derivatives were produced in some naphthaleneacetic acid-treated plants in which
      xylem fiber differentiation was induced and in gibberellic acid-treated plants
      which did not differentiate xylem. When naphthaleneacetic acid was applied 72
      hours after decapitation, the oldest of the cambial derivatives on the xylem side
      failed to develop into fibers although younger cells did. These results suggest
      that auxin has its direct effect on the induction of xylem differentiation rather
      than the induction of divisions prerequisite to differentiation.

PMID- 16657635
TI  - Metabolic and physical control of cell elongation rate: in vivo studies in
      nitella.
AB  - Several levels of control of elongation rate are revealed through the detailed
      study of responses of the Nitella internode to abrupt shifts in turgor. The
      immediate response, which apparently reflects the physical state of the cell, is
      approximately described by the equation r = (P - Y)m where r is rate, P is
      pressure, Y is the wall's yielding threshold, and m is related to the wall's
      apparent fluidity (reciprocal viscosity). Because P and Y are in the range 5 to 6
      atmospheres, and (P - Y) is roughly 0.2 atmosphere, elongation rate is initially
      extremely sensitive to changes in P. A small step-down in turgor (0.7 atmosphere)
      stops growth, and a similar rise greatly accelerates it. These initial responses
      are, however, soon (15 minutes) compensated by changes in Y. An apparent
      metabolism-dependent reaction (azide-sensitive) lowers Y; strain hardening (azide
      insensitive) raises it. These two opposing processes, acting on Y, serve as a
      governor on (P - Y), tending to maintain it at a given value despite changes in
      P. This ability to compensate is itself a function of turgor. Turgor step-downs
      are less and less well compensated, leading to lower rate, as turgor falls from 5
      atmospheres to about 2 atmospheres where growth appears not to resume. This is
      the lowest attainable yield value, Y(1). The turgor dependency of compensation
      reflects a turgor requirement of the Y-lowering ("wall-softening") process. Thus
      the relation between steady state, r(s), and turgor is an indirect one, derived
      from time-dependent alterations of the cell wall. This relationship superficially
      resembles the instantaneously valid one in that, roughly, r(s) = (P - Y(1))m(s).
      Y(1) and m(s), however, have much lower values than Y and m. The duality of the
      elongation rate versus turgor relation and the prominent role of Y in regulating
      rate are the major features of growth control in Nitella.

PMID- 16657636
TI  - Nitrate and the Course of Lemna perpusilla Carbon Dioxide Output under Daily
      Photoperiodic Cycles.
AB  - The carbon dioxide output of Lemna perpusilla 6746 on modified Hutner's media
      under light (dark) cycles of 8 (16) hours is entrained in either of two forms
      depending on the level of nitrate. With nitrate low or absent, the peak occurs
      shortly after the start of each dark period, and the minimum, shortly after the
      start of each light period. With high (about 10 mm) nitrate, an additional or
      sole major peak occurs about 17 hours after the start of each light period; the
      minimum does not shift. This generalization probably also holds for cycles at
      least from 3 (21) to 18 (6). Apparent slow or unstable entrainment in some
      earlier data was undoubtedly a result of the progressive lowering of nitrate in
      the medium and, thus, of the nitrate peak. Future work under stable conditions,
      with or without the nitrate peak, should make possible the more accurate testing
      of models of entrainment and hypotheses concerning photoperiodic timing in this
      and related systems.

PMID- 16657637
TI  - Labeled indole-macromolecular conjugates from growing stems supplied with labeled
      indoleacetic Acid : I. Fractionation.
AB  - Pea (Pisum sativum var. Alaska) and bean (Phaseolus vulgaris var. Red Kidney)
      stem sections treated with indoleacetic acid-1-(14)C, indoleacetic acid-2-(14)C,
      and indoleacetic acid-5-(3)H were homogenized, extracted with phenol, and the
      water-soluble, ethanol-insoluble material subjected to further fractionation.
      Following an 18-hour incubation period in indoleacetic acid-1-(14)C, most of the
      label was found as nonindole-(14)C in high molecular weight polysaccharide, as
      phenol extraction is specific for both RNA and polysaccharides. With indoleacetic
      acid-2-(14)C and -5-(3)H, and to a lesser extent with indoleacetic acid-1-(14)C,
      radioactive indoles were obtained by hydrolysis from a heterogeneous fraction
      between about 500 and 30,000 molecular weight, possibly polysaccharide in nature.
      Indoleacetic acid accounted for 8% and indole aldehyde accounted for 21% of the
      total radioactivity in the extract.

PMID- 16657638
TI  - Induction of phenylalanine ammonia-lyase in xanthium leaf discs: increased
      inactivation in darkness.

PMID- 16657639
TI  - Glutamate dehydrogenase changes in lemna not due to enzyme induction.

PMID- 16657640
TI  - Isolation and Partial Characterization of Ferredoxin from Zea mays.

PMID- 16657641
TI  - Ethylene production from peptides and protein containing methionine.

PMID- 16657642
TI  - Evaluation of water stress control with polyethylene glycols by analysis of
      guttation.
AB  - The water relations of pepper plants (Capsicum frutescens L.) under conditions
      conducive to guttation were studied to evaluate the control of plant water stress
      with polyethylene glycols. The addition of polyethylene glycol 6000 to the
      nutrient solution resulted in water relations similar to those expected in soil
      at the same water potentials. Specifically, xylem pressure potential in the root
      and leaf became more negative during a 24-hour treatment period, while osmotic
      potential of the root xylem sap remained constant. The decrease in pressure
      potential was closely correlated with the decrease in osmotic potential of the
      nutrient solution. In contrast, the addition of polyethylene glycol 400 to the
      nutrient medium resulted in a reduction of osmotic potential in the root xylem
      sap; this osmotic adjustment in the xylem was large enough to establish an
      osmotic gradient for entry of water and cause guttation at a nutrient solution
      osmotic potential of -4.8 bars. Pressure potential in the root and leaf xylem
      became negative only at nutrient solution osmotic potentials lower than -4.8
      bars. About half of the xylem osmotic adjustment in the presence of polyethylene
      glycol 400 was caused by increased accumulation of K(+), Na(+), Ca(2+), and
      Mg(2+) in the root xylem. These studies indicate that larger polyethylene glycol
      molecules such as polyethylene glycol 6000 are more useful for simulating soil
      water stress than smaller molecules such as polyethylene glycol 400.

PMID- 16657643
TI  - Greening of etiolated bean leaves in far red light.
AB  - Eight-day-old dark-grown bean leaves were greened by prolonged irradiation with
      far red light. Growth, chlorophyll content, oxygen-evolving capacity,
      photophosphorylation capacity, chloroplast structure (by electron microscopy),
      and in vivo forms of chlorophyll (by low temperature absorption and derivative
      spectroscopy on intact leaves) were followed during the greening process.
      Chlorophyll a accumulated slowly but continuously during the 7 days of the
      experiment (each day consisted of 12 hours of far red light and 12 hours of
      darkness). Chlorophyll b was not detected until the 5th day. The capacity for
      oxygen evolution and photophosphorylation began at about the 2nd day. Electron
      microscopy showed little formation of grana during the 7 days but rather unfused
      stacks of primary thylakoids. The thylakoids would fuse to give grana if the
      leaves were placed subsequently in white light. The low temperature spectroscopy
      of intact leaves showed that the chlorophyll a was differentiated into three
      forms with absorption maxima near 670, 677, and 683 nanometers at -196 C during
      the first few hours and that these forms accumulated throughout the greening
      process. Small amounts of two longer wavelength forms with maxima near 690 and
      698 nanometers appeared at about the same time as photosynthetic activity.

PMID- 16657644
TI  - Biogenesis and Degradation of Starch: I. The Fate of the Amyloplast Membranes
      during Maturation and Storage of Potato Tubers.
AB  - Storage of mature or developing potato tubers (Solanum tuberosum "Up-to-Date"
      variety) at 4 C causes a reduction in the starch content and the elevation in the
      level of free sugars. This phenomenon is not observed when the tubers are stored
      at 25 C. Changes in the morphology of cells from developing or mature tubers
      after storage at 4 or 25 C have been followed by electron microscopy. During all
      stages of the tuber development the starch granules are surrounded by a membrane
      derived from the plastid envelope. Storage in the cold induces disintegration of
      this membrane. A membrane fraction isolated from starch granules of tubers stored
      at 4 C has a lower buoyant density, and the electrophoretic pattern of its
      proteins is different from that of a similar membrane fraction obtained from
      tubers stored at 25 C. It is suggested that the cold-induced changes in the
      starch and sugar content during storage of potato tubers might be correlated with
      damage to the membranes surrounding the starch granules and changes in their
      permeability to degradative enzymes and substrates.

PMID- 16657645
TI  - Potentiation and inhibition of the effects of 2-chloroethylphosphonic Acid by
      malformin.
AB  - Malformin completely inhibited Ethrel-induced swelling and fresh weight increase
      on the basal stem portion of Phaseolus vulgaris L. cuttings, but markedly
      potentiated Ethrel- or ethylene-induced abscission. With regard to abscission,
      malformin reacted synergistically with ethylene and dark aging, and in a manner
      which appeared to differ from that of ethylene and dark aging. The numerous
      effects of malformin on plant growth and development cannot be explained in
      simple terms of enhanced ethylene production.

PMID- 16657646
TI  - The Conversion of d-Tryptophan to l-Tryptophan in Cell Cultures of Tobacco.
AB  - d-Tryptophan was converted to l-tryptophan in tissue cultures of tobacco, in
      whole cells treated with dimethylsulfoxide, and in cell-free extracts treated by
      Sephadex G-25 filtration. Evidence was obtained that tryptophanase, tryptophan
      pyrrolase, and transaminase activities were not involved. The data were best
      explained by the presence of a tryptophan racemase as the enzyme catalyzing the
      reaction. The possible role of d-tryptophan in the biosynthesis of indoleacetic
      acid is discussed.

PMID- 16657647
TI  - Physiology of Oil Seeds: II. Dormancy Release in Virginia-type Peanut Seeds by
      Plant Growth Regulators.
AB  - Germination, ethylene production, and carbon dioxide production by dormant
      Virginia-type peanuts were determined during treatments with plant growth
      regulators. Kinetin, benzylaminopurine, and 2-chloroethylphosphonic acid induced
      extensive germination above the water controls. Benzylaminopurine and 2
      chloroethylphosphonic acid increased the germination of the more dormant basal
      seeds to a larger extent above the controls than the less dormant apical seeds.
      Coumarin induced a slight stimulation of germination while abscisic acid, 2,4
      dichlorophenoxyacetic acid, and succinic acid 2,2-dimethylhydrazide did not
      stimulate germination above the controls. In addition to stimulating germination,
      the cytokinins also stimulated ethylene production by the seeds. In the case of
      benzylaminopurine, where the more dormant basal seeds were stimulated to
      germinate above the control to a larger extent than the less dormant apical
      seeds, correspondingly more ethylene production was induced in the basal seeds.
      However, the opposite was true of kinetin for both germination and ethylene
      production. When germination was extensively stimulated by the cytokinins,
      maximal ethylene and carbon dioxide evolution occurred at 24 and 72 hours,
      respectively. Abscisic acid inhibited ethylene production and germinaton of the
      seeds while carbon dioxide evolution was comparatively high. The crucial
      physiological event for germination of dormant peanut seeds was enhancement of
      ethylene production by the seeds.

PMID- 16657648
TI  - De novo synthesis of peroxidase isozymes in sweet potato slices.
AB  - The peroxidase content of sweet potato slices (Ipomoea batatas Lam.) increased
      nearly 100-fold following 84 hours incubation in an air atmosphere containing
      ethylene, 1 microliter per liter. The object of experiments reported here is to
      determine if this increase in peroxidase activity results from synthesis de novo
      of the enzyme or from activation of a preexisting inactive form of the enzyme.The
      enzymatic activity of each peroxidase isozyme increased during the incubation
      period, and each peroxidase isozyme appeared to incorporate (14)C-leucine.
      Polyacrylamide gel electrophoresis of the neutral peroxidase fraction showed that
      all peroxidase activity and essentially all radioactivity migrated as a single
      superimposable band. The other peroxidase fractions were less pure. Treatment of
      fresh slices, or slices collected midway in the time course with the inhibitor of
      protein synthesis, blasticidin S, (1 microgram per milliliter for one minute)
      caused an abrupt cessation of peroxidase formation and simultaneously an abrupt
      cessation of incorporation of (14)C-leucine into peroxidase isozymes. These
      observations indicate that the rapid increase in peroxidase activity in sweet
      potato slices results from synthesis de novo of the enzyme.

PMID- 16657649
TI  - Mass isolation of pea nuclei.
AB  - Improvements in conventional filtration and centrifugation procedures made it
      possible to increase the yield of intact cytoplasm-free pea (Pisum sativum)
      nuclei from the usual 3 to 10% to 32% (6 x 10(8) nuclei per 7 grams fresh weight
      of pea apices) and to complete the isolation in 80 to 90 minutes. The isolated
      nuclei appeared to retain their structural integrity as revealed in electron
      photomicrographs, and remained intact for at least 5 hours at 20 Celsius.The
      DNA:RNA: protein ratio of isolated pea nuclei was found to be 3.1:1:9.9. Their
      RNA polymerase activity, monitored by incorporation of (14)C into RNA from (14)C
      UTP, was linear for about 10 minutes, and then gradually declined over the next
      15 to 20 minutes.

PMID- 16657650
TI  - Mechanism of Auxin-induced Ethylene Production.
AB  - Indoleacetic acid-induced ethylene production and growth in excised segments of
      etiolated pea shoots (Pisum sativum L. var. Alaska) parallels the free
      indoleacetic acid level in the tissue which in turn depends upon the rate of
      indoleacetic acid conjugation and decarboxylation. Both ethylene synthesis and
      growth require the presence of more than a threshold level of free endogenous
      indoleacetic acid, but in etiolated tissue the rate of ethylene production
      saturates at a high concentration and the rate of growth at a lower concentration
      of indoleacetic acid. Auxin stimulation of ethylene synthesis is not mediated by
      induction of peroxidase; to the contrary, the products of the auxin action which
      induce growth and ethylene synthesis are highly labile.

PMID- 16657651
TI  - Fat Metabolism in Higher Plants: XLV. Some Factors Regulating Fatty Acid
      Synthesis by Isolated Spinach Chloroplasts.
AB  - In the biosynthesis of fatty acids from 1-(14)C-acetate by intact spinach
      chloroplasts, ATP and Triton X-100 exert opposing effects on the conversion of
      palmitic acid to stearic acid; thus, ATP decreases the conversion and Triton X
      100 increases the conversion. Changes in the availability of photosynthetically
      generated reduced nicotinamide adenine dinucleotide phosphate apparently does not
      markedly affect the C(16)-C(18) ratio. Various H(2)O(2)-generating systems, such
      as viologen dyes, inhibit oleate synthesis from acetate and cause stearate to
      accumulate. Catalase partially reverses the effect of these days.

PMID- 16657652
TI  - The Metabolism of Hormones during Seed Germination and Dormancy: II. The
      Metabolism of 8-C-Zeatin in Bean Axes.
AB  - 8-(14)C-Zeatin is taken up rapidly and is extensively metabolized by excised bean
      axes during a 12-hour incubation at 26 C. Most of the radioactivity is found in
      the 80% ethanol soluble fraction and consists of zeatin, zeatin riboside, zeatin
      5'-ribotide, as well as corresponding dihydrozeatin derivatives. The
      characterization of (14)C-dihydrozeatin included crystallization to constant
      specific radioactivity. No cleavage of the zeatin side chain to adenine,
      hypoxanthine, their ribosides, or glycylpurine was detected. Dihydrozeatin has
      been previously isolated from yellow lupin seeds, and our experiments indicate
      that it can be derived through reduction of the side chain from preexisting
      cytokinin. While the total amount of zeatin metabolized is not affected by growth
      inhibiting concentrations of abscisic acid or cycloheximide, the conversion to
      dihydrozeatin derivatives is curtailed. Although somewhat less effective than
      zeatin and zeatin riboside, dihydrozeatin and dihydrozeatin riboside also
      counteract the abscisic acid-induced growth inhibition.

PMID- 16657653
TI  - Enhancement of germination rate of aged seeds by ethylene.
AB  - Naturally and artificially aged seeds of rape, Brassica napus L., produced less
      ethylene than freshly harvested seed during the early stage of germination. With
      freshly harvested seeds one peak of ethylene production was observed during
      germination, which coincided with the emergence and elongation of root and
      cotyledon, accompanied by splitting of the seed coat. Application of exogenous
      ethylene was effective in accelerating germination in aged seeds but did not
      significantly improve the percentage of germination. Ethylene as a hormone was
      considered to serve as a stimulator of germination and growth. One of the factors
      causing seed aging might be the degeneration of an ethylene-producing system in
      the seed. Exogenous ethylene may be effective only for the seeds in which the
      ethylene-producing system is weakened but the following responding systems are
      still functional.

PMID- 16657654
TI  - Bicarbonate Fixation and Malate Compartmentation in Relation to Salt-induced
      Stoichiometric Synthesis of Organic Acid.
AB  - The relationship of malate synthesis to K(+) absorption from solutions of
      K(2)SO(4) and KHCO(3) was compared in nonvacuolate barley (Hordeum vulgare) root
      tips and whole excised roots. The comparison has permitted separation of the
      process which evokes organic acid synthesis from that which leads to
      stoichiometry between net acid equivalents formed and excess K(+) absorbed from
      K(2)SO(4), on the one hand, and total K(+) absorbed from KHCO(3), on the other.
      Both in tips and in roots K(+) uptake from 20 mN salt solution exceeds malate
      synthesis in the first hour. In vacuolate roots the expected stoichiometry is
      achieved with time. When root tips are transferred to dilute CaSO(4), malate is
      rapidly metabolized, and K(+) is lost to the solution. By contrast, in excised
      whole roots the malate level remains unchanged, the salt-induced organic acid
      presumably being retained in the vacuole. In excised roots malonate leads to a
      marked drop in malate levels in untreated roots as well as in roots which have
      experienced salt-induced net malate synthesis. In consequence, it is contended
      that malonate makes available normally sequestered vacuolar malate.The general
      hypothesis is offered that the bicarbonate level of the cytoplasm controls
      organic acid synthesis by phosphoenolpyruvate carboxylase, and that the
      cytoplasmic bicarbonate level is raised either by exchange of cytoplasmic H(+)
      for external cation, or by bicarbonate absorption directly. Stoichiometry, in
      turn, is achieved by the accumulation in the vacuole of the double salt of
      malate.

PMID- 16657655
TI  - Adenosine triphosphatase activity associated with mung bean mitochondria.
AB  - The properties of the adenosine triphosphatase activity associated with tightly
      coupled, time-stable mung bean (Phaseolus aureus Roxb.) mitochondria resemble
      those of intact animal mitochondria. Induction of adenosine triphosphatase
      activity by 2,4-dinitrophenol was inhibited by oligomycin, oxidizable substrates,
      and high concentrations of sucrose. Upon sonication, high rates of endogenous
      adenosine triphosphate hydrolysis resulted, an absolute requirement for Mg(2+)
      was manifested, stimulation by 2,4-dinitrophenol and inhibition by sucrose were
      eliminated, but sensitivity to oligomycin was retained.

PMID- 16657656
TI  - Regulation by auxin of carbohydrate metabolism involved in cell wall synthesis by
      pea stem tissue.
AB  - Promotion of cell wall synthesis (from glucose) in pea (Pisum sativum) stem
      segments by indoleacetic acid (IAA) develops over a period of 1 to 2 hours and is
      comprised of a promotion of glucose uptake plus a promotion of the utilization of
      absorbed glucose. The effect of IAA resembles, in these and other respects, its
      effect on cell wall synthesis in oat coleoptile segments, but the pea system
      differs in not being inhibited by galactose or mannose, in involving considerably
      more isotope dilution by endogenous substrates, and in certain other
      respects.EFFECTOR INFLUENCES UPON AND TOTAL ACTIVITIES OF THE FOLLOWING ENZYMES
      OBTAINED FROM ETIOLATED PEA STEM SEGMENTS PRETREATED WITH OR WITHOUT IAA WERE
      EXAMINED: phosphoglucomutase, uridine diphosphate glucose (UDP-glucose)
      pyrophosphorylase, nucleoside diphosphokinase, UDP-glucose dehydrogenase,
      inorganic pyrophosphatase, hexokinase (particulate and soluble), and UDP-glucose
      beta-1,4-glucan-glucosyl transferase (beta-glucan synthetase). The first three
      enzymes mentioned exhibit high activity relative to the flux in vivo, do not
      appear to show physiologically significant effector responses, and are concluded
      not to be control points. UDP-glucose dehydrogenase activity is regulated by UDP
      xylose. Hexokinase is a potential control point but does not exhibit regulatory
      effects related to the IAA response. beta-Glucan synthetase is the only one of
      these enzymes with activity which is increased by treatment of tissue with IAA,
      and this may be responsible for the effect of IAA on wall synthesis.Assays of
      metabolite pools support the conclusion that stimulation of polysaccharide
      synthesis by IAA is due partly to changes in hexokinase reaction rate resulting
      from an increase in metabolic glucose pool size caused by increased glucose
      uptake, and partly to increased activity at the polysaccharide synthetase level.

PMID- 16657657
TI  - Response to selenium by callus cultures derived from astragalus species.
AB  - Callus cultures were obtained from five selenium accumulator and three
      nonaccumulator species of Astragalus. Their morphological characteristics and
      their growth responses to light, sucrose, kinetin, and 2,4-dichlorophenoxyacetic
      acid are described. Calluses derived from accumulator species characteristically
      retained their tolerance to high concentrations of selenate and selenite, whereas
      calluses derived from nonaccumulator species were markedly inhibited by these two
      forms of selenium. Competition between sulfate and selenate was demonstrated. The
      two types of calluses could not be distinguished on the basis of (75)Se-labeled
      selenate or selenite uptake. Neutron activation analysis failed to show
      differences in selenium content between the two types of calluses grown on media
      to which no selenium had been added.

PMID- 16657658
TI  - Induction of alpha-amylase in barley endosperm by substrate levels of glutamate
      and aspartate.
AB  - Incubation of embryoless barley (Hordeum vulgare) half-seeds for 24 hours with
      0.1 m glutamate or aspartate resulted in the release of 17 to 48% as much alpha
      amylase as did incubation with 260 mmum gibberellin. With incubation periods of
      48 to 51 hours these amino acids were on the average about half as active as
      response-saturating concentrations of gibberellin, and in some experiments they
      were essentially as active. Citric acid cycle intermediates, glycolytic pathway
      intermediates, and cofactors of these pathways failed to induce alpha-amylase
      synthesis, while the following compounds were active: asparagine, homoserine,
      diaminopimelate, isoleucine, methionine, glutamine, ornithine, citrulline,
      argininosuccinate, and delta-aminolevulinate. However, threonine, lysine, beta
      alanine, alanine, gamma-aminobutyrate, alpha-ketobutyrate, proline, arginine,
      glycine, leucine, and putrescine were inactive. Two patterns were noted in the
      list of active and inactive compounds: (a) all of the active compounds contain an
      amino group and are biosynthetically derived from citric acid cycle
      intermediates; and (b) biosynthetic precursors of the amino acids arginine,
      proline, threonine, and lysine were active whereas these amino acids were not.

PMID- 16657659
TI  - Role of Potassium in Stomatal Opening in the Leaf of Vicia faba.
AB  - With isolated epidermal strips of Vicia faba, the intensity of potassium-staining
      in the guard cells of stomata was calibrated against the uptake of radioactively
      labeled potassium. By using this calibration, the quantity of potassium that had
      accumulated in the guard cells, as stomata of leaves of Vicia open in the light,
      was estimated. Results support the hypothesis that in leaves, as well as in
      isolated epidermal strips, potassium and an accompanying anion comprise the
      major, osmotically active solutes in the guard cells of open stomata.

PMID- 16657660
TI  - Leaf temperature effects on measurements of diffusive resistance to water vapor
      transfer.
AB  - Substantial errors can be introduced to estimates of leaf resistance (r(l))
      obtained from diffusion porometers unless precautions are taken to reduce the
      leaf-cup temperature difference (T(leaf) - T(cup)) to acceptable levels prior to
      measurement. When T(leaf) > T(cup), underestimation of leaf resistance occurs;
      the reverse applies when T(leaf) < T(cup).The effect is most pronounced under
      open-stomata conditions and declines as stomatal resistance increases. Under
      typical measurement conditions, T(leaf) - T(cup) values of the order of 1 C
      induce a reduction in the ratio of the apparent to true leaf resistance to about
      0.8 when the leaf resistance is low (r(l) = 1-2 sec cm(-1)). When T(leaf) -
      T(cup) = 5 C, the ratio drops below 0.5. Under high leaf resistance conditions
      (r(l) = 10-50 sec cm(-1)) the comparable ratios are approximately 0.9 and 0.7,
      respectively.

PMID- 16657661
TI  - Kinetin and carbohydrate metabolism in chinese cabbage.
AB  - The effects of kinetin on starch and sugar levels and on (14)CO(2) and (32)P
      orthophosphate labeling patterns of floated Chinese cabbage (Brassica pekinensis)
      leaf discs were investigated. Kinetin caused gross starch degradation. Neutral
      sugars were depressed by 30 to 40% in leaf tissue treated with kinetin for 24
      hours. (14)CO(2) labeling of leaf discs pretreated with kinetin for 24 hours
      showed increased radioactivity in chloroform-soluble material and most sugar
      phosphates, and a 35 to 40% decrease in radioactivity in the neutral sugars,
      glucose, sucrose, and fructose. Incorporation into ATP was increased by 40% by
      kinetin. (32)P-Orthophosphate uptake was inhibited 30% by kinetin. When corrected
      for uptake, kinetin stimulated incorporation into chloroform-soluble material but
      had little effect on other cell fractions. These results indicate that kinetin
      mobilizes starch reserves and increases the flow of sugars required for the
      synthesis of lipids and structural materials in floated discs.

PMID- 16657662
TI  - Effects of Hydroxylamine on Photosystem II: I. Factors Affecting the Decay of
      O(2) Evolution.
AB  - Illumination of chloroplasts in the presence of NH(2)OH (2 mm) leads to the
      destruction of all system II activities without affecting system I activity. The
      system II primary charge separation remains intact when incubated with this agent
      in the dark with release of one of the system II Mn pools and simultaneous
      destruction of O(2) evolving capacity. The size of the Mn pool associated with
      the O(2) evolving center is calculated to be 4 Mn/O(2)-evolving center.We
      observed the following properties of the hydroxylamine-induced destruction of
      O(2) centers in darkness: [List: see text]Chloroplasts from summer greenhouse
      spinach (4-5 Mn/400 chl(total) or 50 to 60% of the Mn pool of the O(2)-evolving
      center) showed high quantum requirement for O(2) evolution (5-6 hv/equivalent)
      yet photooxidized NH(2)OH with low quantum requirement ( approximately 2
      hv/equivalent).

PMID- 16657663
TI  - An evaluation of 4-s-methyl-2-keto-butyric Acid as an intermediate in the
      biosynthesis of ethylene.
AB  - Stimulation of ethylene production by cauliflower (Brassica oleracea var.
      botrytis L.) tissue in buffer solution containing 4-S-methyl-2-keto-butyric acid
      is not due to activation of the natural in vivo system. Increased ethylene
      production derives from an extra-cellular ethylene-forming system, catalyzed by
      peroxidase and other factors, which leak from the cauliflower tissue and cause
      the degradation of 4-S-methyl-2-keto-butyric acid. This exogenous ethylene
      forming system is similar to the ethylene-forming horseradish peroxidase system
      which utilizes methional or 4-S-methyl-2-keto-butyric acid as substrate. We
      conclude that 4-S-methyl-2-keto-butyric acid is probably not an intermediate in
      the biosynthetic pathway between methionine and ethylene.

PMID- 16657664
TI  - Chromatographic analysis of a cytokinin from tissue cultures of crown-gall.
AB  - Extracts from tissue cultures of crown-gall from Parthenocissus tricuspidata
      (Sieb. and Zucc.) Planch. exhibited cell division activity in the soybean
      cytokinin assay. The chromatographic migration of one component, responsible for
      most of the activity, is similar to that of zeatin ribonucleoside. In addition,
      acid hydrolysis of the active region taken from chromatograms and of an eluate
      from a cation-exchange resin column resulted in the production of an active free
      base-like derivative. Since the derivative and the parent compound lose activity
      after KMnO(4) treatment, they are believed to possess an unsaturated constituent
      essential for biological activity. The major active factor present in crown-gall
      from Parthenocissus tricuspidata is therefore distinct from the nicotinamide
      derivative reported to be present in Vinca rosea L. tumor cells.

PMID- 16657665
TI  - Ammonium Ion and the Flowering of Lemna perpusilla.

PMID- 16657666
TI  - Ultraviolet Light-induced Formation of Pisatin and Phenylalanine Ammonia Lyase.

PMID- 16657667
TI  - Large Effects of Small Water Deficits on Chlorophyll Accumulation and Ribonucleic
      Acid Synthesis in Etiolated Leaves of Jack Bean (Canavalia ensiformis [L.] DC.).

PMID- 16657668
TI  - Changes in total nitrogen, soluble protein, and peroxidases in the expanding leaf
      zone of eastern cottonwood.
AB  - Nitrogen content and soluble protein and anodal peroxidase banding in acrylamide
      gel changed with leaf and internode development in the expanding leaf zone of
      eastern cottonwood (Populus deltoides Bartr.). Nitrogen per unit leaf area was
      high near the apex and decreased to a constant value at the sixth node below it.
      Soluble protein banding was qualitatively similar for leaves and internodes in
      this zone, but anodal peroxidases differed between leaves and internodes. The
      major leaf peroxidase band was absent from the second leaf below the apex but
      present in the fourth and sixth leaves; its appearance and intensification seemed
      to parallel the development of photosynthetic activity. The major internode
      peroxidase band was present in the apex, second, fourth, and sixth internodes,
      and intensified during internodal development. It is suggested that these two
      "isoenzymes" may have different functions in vivo.

PMID- 16657669
TI  - Spectral, Physical, and Electron Transport Activities in the Photosynthetic
      Apparatus of Mesophyll Cells and Bundle Sheath Cells of Digitaria sanguinalis
      (L.) Scop.
AB  - Isolated mesophyll cells and bundle sheath cells of Digitaria sanguinalis were
      used to study the light-absorbing pigments and electron transport reactions of a
      plant which possesses the C(4)-dicarboxylic acid cycle of photosynthesis.
      Absorption spectra and chlorophyll determinations are presented showing that
      mesophyll cells have a chlorophyll a-b ratio of about 3.0 and bundle sheath cells
      have a chlorophyll a-b ratio of about 4.5. The absorption spectrum of bundle
      sheath cells has a greater absorption in the 700 nm region at liquid nitrogen
      temperature, and there is a relatively greater amount of a pigment absorbing at
      670 nm in the bundle sheath cells compared to the mesophyll cells. Fluorescence
      emission spectra, at liquid nitrogen temperature, of mesophyll cells have a
      fluorescence 730 nm-685 nm ratio of about 0.82 and bundle sheath cells have a
      ratio of about 2.84. The reversible light-induced absorption change in the region
      of P(700) absorption is similar in both cell types but bundle sheath cells
      exhibit about twice as much total P(700) change as mesophyll cells on a total
      chlorophyll basis. The delayed light emission of bundle sheath cells is about one
      half that of mesophyll cells. Both mesophyll cells and bundle sheath cells evolve
      oxygen in the presence of Hill oxidants with the mesophyll cells exhibiting about
      twice the activity of bundle sheath cells, and both activities are inhibited by 1
      muM 3-(3,4-dichlorophenyl)-1, 1-dimethylurea. Ferredoxin nicotinamide adenine
      dinucleotide phosphate reductase is present in both cells although it is about 3-
      or 4-fold higher in mesophyll cells than in bundle sheath cells. Glyceraldehyde 3
      P dehydrogenases, both nicotinamide adenine dinucleotide and nicotinamide adenine
      dinucleotide phosphate, are equally distributed in the two cell types on a
      chlorophyll basis. Malic enzyme is localized in the bundle sheath cells.We
      interpret the data as evidence for the presence of a complete chloroplast
      electron transport system from oxygen evolution to pyridine nucleotide reduction
      in both mesophyll and bundle sheath cells. However, there is a quantitative
      difference in the distribution of photosystem I and photosystem II components in
      the two photosynthetic cells with about a 3-fold higher photosystem I-II ratio in
      the bundle sheath cells than in the mesophyll cells. A scheme is proposed to
      accommodate photosynthetic CO(2) fixation and electron transport activities in
      the mesophyll cells via a beta-carboxylation and in the bundle sheath cells via
      carboxylation of ribulose-1, 5-diphosphate.

PMID- 16657670
TI  - Inhibition of Auxin-induced Deoxyribonucleic Acid Synthesis and Chromatin
      Activity by 5-Fluorodeoxyuridine in Soybean Hypocotyl.
AB  - Rootless soybean (Glycine max) seedlings were used as a test system to examine
      the action of auxin on chromatin-directed RNA synthesis. Chromatin from the basal
      tissue of rootless seedlings (both control and auxin-treated) had RNA synthetic
      capacity similar to that of chromatin from comparably treated intact seedlings.
      When DNA synthesis normally induced in the basal tissue by auxin was blocked in
      the rootless seedlings by 5-fluorodeoxyuridine, the auxin enhancement of
      chromatin activity was inhibited 70%. This level was still three times the
      control level, indicating that auxin influenced the synthetic activity of
      existing DNA template. Experiments with Escherichia coli RNA polymerase revealed
      that chromatin from both auxin- and auxin plus 5-fluorodeoxyuridine-treated
      tissue saturated at higher levels than chromatin from control tissue.

PMID- 16657671
TI  - Purification and Properties of Chlorophyllase from Ailanthus altissima (Tree-of
      Heaven).
AB  - Chlorophyllase from Ailanthus altissima leaves has been purified 63-fold by a
      combination of heat treatment, ultracentrifugation, gel filtration, and
      chromatography on diethylaminoethyl cellulose. While the enzyme is inhibited to
      some degree by Triton X-100, a modification of the assay procedure of Klein and
      Vishniac has been shown to be far superior to the use of aqueous acetone systems.
      The enzyme was found to have a pH optimum on pheophytin a of 4.5. Chlorophylls a
      and b, pheophytins a and b, and pyropheophytin a were hydrolyzed by the enzyme
      while protochlorophyll a and 4-vinyl protochlorophyll a were not hydrolyzed but
      were competitive inhibitors. p-Nitrophenyl acetate was not hydrolyzed. The enzyme
      does not appear to contain an essential sulfhydryl group since sodium
      tetrathionate and p-chloromercuribenzoate did not affect its activity.

PMID- 16657672
TI  - Changes in Phytochrome Expressed by Germination of Amaranthus retroflexus L.
      Seeds.
AB  - Effects of red (600 to 680 nanometers) and far red (700 to 760 nanometers)
      irradiances on Amaranthus retroflexus L. seeds indicate that synthesis of
      phytochrome in the red-absorbing form takes place in water-imbibed nongerminating
      seeds at 35 C. After 96 hours in darkness, conversion of about 0.10% phytochrome
      to the far red-absorbing form induces 50% germination. Continuous far red
      radiation at 35 C with an irradiance of 0.4 x 10(-10) Einsteins per square
      centimeter per second caused photoinactivation of phytochrome about equal to the
      rate of synthesis. Germination of seeds at 35 C, following far red irradiation
      adequate to establish the photostationary state, is enhanced by holding at 26 C
      for 16 minutes. Germination is unaffected relative to controls at constant
      temperature, if the period at 26 C precedes irradiation. The results indicate a
      quick response to action of phytochrome in a germination process.

PMID- 16657673
TI  - Invertase Activity in Normal and Mutant Maize Endosperms during Development.
AB  - A bound invertase and two soluble invertases are found in the developing
      endosperm of maize (Zea mays L.). The two soluble invertases can be separated on
      diethylaminoethyl-cellulose and Sephadex columns and distinguished by their
      kinetic constants. One soluble invertase, invertase I, is present from the 10- to
      28-day stages of endosperm development with maximal activity per normal endosperm
      at the 12-day stage. In two endosperm mutant lines, shrunken-1 and shrunken-2,
      there is a second increase in invertase I activity later in development which
      could be a secondary effect caused by the abnormal metabolism in these lines.
      Another soluble invertase, invertase II, is present in the embryo upon
      germination and is also found in the very young developing endosperm (6-day
      stage). The third form of invertase, bound invertase, is present in the endosperm
      by the 6-day stage, and its activity remains approximately constant during
      development.

PMID- 16657674
TI  - An invertase inactivator in maize endosperm and factors affecting inactivation.
AB  - A protein present in the developing endosperm of maize (Zea mays L.) causes a
      loss of invertase activity under certain conditions of incubation. This protein,
      designated an inactivator, inactivates invertase I of maize even in the presence
      of other proteins. No inactivation of invertase II of maize or yeast invertase
      has been observed. The inactivator and invertase I are found only in the
      endosperm. The quantity of inactivator increases in the normal endosperm during
      development while invertase I activity decreases. However, the altered levels of
      invertase I activity in several endosperm mutant lines do not result from
      different quantities of inactivator. The inactivator can decrease invertase I
      activity during a preincubation period before addition of sucrose; inactivation
      is noncompetitive. Invertase I activity decreases curvilinearly with an increase
      in inactivator concentration. At high buffer concentrations or low inactivator
      concentrations in the reaction mixture, a latent period is observed when
      invertase I is not inactivated. Inactivation increases with an increase in
      temperature and a decrease in pH.

PMID- 16657675
TI  - Photosynthetic products of division synchronized cultures of euglena.
AB  - Rates and products of photosynthetic (14)CO(2) fixation by division synchronized
      cultures of Euglena gracilis strain Z were determined over the cycle. Rate of
      (14)CO(2) fixation doubled in a continuous manner throughout the light phase
      followed by a slight reduction of photosynthetic capacity in the dark phase.
      Greater (14)C incorporation into the nucleic acid-polysaccharide fraction
      occurred with mature cells. Products of (14)CO(2) fixation varied markedly over
      the cycle: although with mature cells (14)C-labeled sucrose was not detected,
      with dividing cells this was the main sugar labeled; in young cells (14)C maltose
      was formed. Cells removed at end of dark phase accumulated (14)C in glycolate,
      whereas at other stages over the cycle less (14)C was present in glycolate, and
      this was accompanied by a rapid incorporation of (14)C into glycine and serine.
      Glycerate was an early and major product of photosynthesis with cells at the
      mature stage of the cycle.Changes in ribulose 1,5-diphosphate carboxylase
      activity paralleled changes in photosynthetic rate, but activity was not great
      enough to account for the observed rates of CO(2) fixation at most stages of the
      division cycle investigated.

PMID- 16657676
TI  - The regulation of glycolate metabolism in division synchronized cultures of
      euglena.
AB  - Phosphoglycolate and phosphoglycerate phosphatases and glycolate dehydrogenase
      activities were determined in division synchronized Euglena gracilis strain Z
      cultures. Phosphoglycolate phosphatase activity remained nearly constant in the
      light but doubled in the dark, whereas phosphoglycerate phosphatase activity
      decreased by half in the light and increased 4-fold over the dark phase of the
      cycle. Glycolate dehydrogenase activity assayed by dye reduction increased over
      the light and remained constant during the dark phase, but when determined by the
      phenylhydrazone method, an assay dependent upon the presence of a natural
      hydrogen acceptor, activity decreased in the dark phase. The acceptor decayed in
      the dark in all cell-free extracts and 3-(3,4-dichlorophenyl)-1, 1-dimethylurea
      inhibited light regeneration.Enzyme activity regulated flow of carbon via the
      glycolate pathway; with cells at end of light phase and early dark phase, high
      levels of glycolate dehydrogenase activity were accompanied by an early and rapid
      labeling of glycerate. Degradation of early samples gave uniformly labeled
      glycolate and glycerate while phosphoglycerate was predominantly carboxyl
      labeled. At these stages in the division cycle, glycerate was formed from
      glycolate via the glycolate pathway, all the enzymes of the pathway being
      recorded in Euglena. In contrast to cells from end of dark phase and early light
      phase, times of maximum phosphoglycerate phosphatase activity, glycerate was
      predominantly carboxyl labeled as was phosphoglycerate, but glycolate was still
      uniformly labeled.Glycolate excretion varied over the cycle, being maximal at end
      of dark phase, decreasing throughout the light phase until not detectable in
      early dark phase. When alpha-hydroxy-2-pyridinemethanesulfonate was used as a
      measure of glycolate biosynthesis, sufficient glycolate dehydrogenase was present
      to oxidize the glycolate produced at all stages over the cycle.

PMID- 16657677
TI  - Purification and Properties of Amine Oxidase from Epicotyls of Pisum sativum.
AB  - A procedure has been developed for the purification of amine oxidase (E.C.
      1.4.3.4) from etiolated pea epicotyls (Pisum sativum cv. Little Marvel). The
      enzyme is sensitive to copper chelating reagents and carbonyl reagents, but is
      not inhibited by sulfhydryl reagents. The purified enzyme has a molecular weight
      of 1.85 x 10(5), as determined by sedimentation equilibrium centrifugation, and
      has been shown to be specifically stimulated by phosphate.

PMID- 16657678
TI  - An Analysis of Phytochrome-mediated Anthocyanin Synthesis.
AB  - Phytochrome (far red form) alone can mediate anthocyanin synthesis in the mustard
      seedling (Sinapis alba L.). Complete photoreversibility and reciprocity, for both
      red and far red light exposures over a period of at least 5 minutes, demonstrate
      this phytochrome involvement.The duration of the initial lag-phase is constant
      (about 3 hours at 25 C) for seedlings more than 30 hours old and is specific for
      the system, being independent of the dose or quality of light. Since a complete
      reversal by far red of a red light induction is possible only during a 5 minute
      period, phytochrome (far red form) obviously mediates anthocyanin synthesis
      during the lag-phase although the actual synthesis of pigment can proceed only
      after the lag-phase is overcome. We suggest that phytochrome (far red form)
      exerts a double function during the initial lag-phase. It mediates both the build
      up of a biosynthetic potential ("capacity") and anthocyanin synthesis. However,
      the sequence of events leading to anthocyanin is arrested at some intermediate
      stage until this "capacity" is built up after 3 hours. Once "capacity" is
      achieved it does not decay readily. Therefore, no significant "secondary lag
      phase" occurs if the seedling, under appropriate conditions, is reirradiated
      after an intervening dark period. The rate or extent of synthesis for both
      anthocyanin and lipoxygenase, previously reported (32), are functions of the
      amount of phytochrome (far red form). No "phytochrome paradoxes," i.e.,
      nonrational relationships between the amount of phytochrome (far red form) and
      rate or extent of response, were detected. This fact suggests that the mustard
      seedling is especially well suited for investigating the biophysical and
      molecular mechanisms of phytochrome action.

PMID- 16657679
TI  - Reflectance and transmittance of light by leaves.
AB  - Spectrophotometric transmittance and reflectance curves were recorded for
      wavelengths from 0.45 (in some cases 0.34) to 2.7 micrometers for faces and backs
      of leaves and for stacked leaves of several plant species. Measurements were made
      at different angles of illumination. Leaf spectrophotometric curves were compared
      with curves for leaf extracts, potato tuber tissue, glass beads in water, and
      frozen leaves to demonstrate the physical bases for the leaf curves. Leaves were
      infiltrated with liquids of different refractive indices for further comparison
      of spectrophotometric curves. Goniophotometric reflectance curves were recorded,
      giving visible reflectance and degree of polarization as functions of viewing
      angle for two different angles of illumination.No retroreflection was observed,
      and no phenomena were observed which could be attributed to interference because
      of similarity between leaf structural sizes and wavelengths used.

PMID- 16657680
TI  - Investigation of respiratory and ion transport properties of aging bean stem
      slices.
AB  - Ion and oxygen uptake were studied on aging bean stem slices. Oxygen uptake was
      high immediately after slicing, decreased to a minimum at 100 minutes, and then
      increased again. Ion uptake per unit of O(2) uptake data suggested that metabolic
      energy was utilized almost exclusively for sodium transport in fresh tissue but
      was diverted to potassium transport as the slices aged. Oxygen and ion uptake in
      fresh slices was less sensitive to 2,4-dinitrophenol as compared to the aged
      slices, indicating major metabolic and physiological changes occurred during
      aging. This was further substantiated by the tissue response to cyanide and
      antimycin A. Oxygen uptake was decreased by cyanide (22% by 1 mm) and antimycin A
      (14% by 1 microgram per milliliter) in fresh slices but not in aged slices.
      Potassium uptake that developed during aging was sensitive to cyanide and
      antimycin A. The results are pertinent to understanding the role of the stem in
      regulating ion transport in plants.

PMID- 16657681
TI  - Red and far red effects on phenylalanine ammonia-lyase in raphanus and sinapis
      seedlings do not correlate with phytochrome spectrophotometry.
AB  - In seedlings of Raphanus sativus (radish) and Sinapis alba (mustard), irradiation
      for 6 hours with far red light significantly increases the extractable activity
      of phenylalanine ammonia-lyase by the end of the light period. A schedule of 10
      minutes red light-110 minutes darkness-10 minutes red-110 minutes darkness-10
      minutes red-110 minutes darkness has no effect as compared to dark controls.
      However, the red light program maintains a level of far red-absorbing phytochrome
      always measurable by in vivo spectrophotometry during the 6-hour experimental
      period. We conclude that the far red effect on this enzyme and for this specific
      material cannot be explained solely by formation and maintenance of far red
      absorbing phytochrome.

PMID- 16657682
TI  - The pentose phosphate pathway in relation to fat synthesis in the developing
      castor oil seed.
AB  - Slices of 25- to 28-day-old developing castor bean endosperm were incubated with
      various (14)C- and (3)H-labeled substrates to determine the amount of glucose
      dissimilated in the pentose phosphate pathway and to determine the use of the
      reduced nucleotides so produced in fatty acid synthesis. Ten to 12% of the
      metabolized glucose traversed the pentose phosphate pathway, and reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) production would be
      sufficient to supply 51 to 68% of the reducing equivalents required for fat
      synthesis. However, using (3)H-NADPH produced from 3-(3)H-glucose as a tracer, it
      was found that only 40% of the NADPH produced in the pentose phosphate pathway
      was used in fat synthesis. Thus the actual contribution of the reducing
      equivalents generated from the pentose phosphate pathway to fat synthesis was 20
      to 27% of that required. Because of the methods and assumptions, this value
      represents a minimal estimate of NADPH used in fat synthesis, and the actual
      contribution may be somewhat higher. However, tritium from (3)H-NADH generated
      from 1-(3)H-ethanol was incorporated into fatty acids, and it is contended that
      NADH may supply a large proportion of the reducing equivalents necessary for fat
      synthesis in this tissue.

PMID- 16657683
TI  - Rhythmic leaf movements in biloxi soybean and their relation to flowering.
AB  - The rhythmic leaf movement of Biloxi soybean (Glycine max) and its relationship
      to the rhythmic flowering response were studied. The movements of fully expanded
      trifoliate leaves were recorded with kymographs and time lapse photography in
      growth chambers. A comparison between the leaf movement rhythm and the rhythmic
      flowering response indicates that a high degree of similarity exists between the
      two rhythms. A definite relationship was shown to exist between the direction of
      the leaf movement and the photophil-photophobe phases of the rhythmic flowering
      response.Short light perturbations may affect flowering by interacting directly
      with the flowering process while not affecting the basic endogenous rhythm. Long
      light perturbations may affect flowering by phase shifting the basic endogenous
      rhythm. Thus, light perturbations appear to have a dual effect on the flowering
      response of Biloxi soybean. The hypothesis that both the flowering rhythm and the
      leaf movement rhythm are coupled to the same basic oscillator is supported by the
      similarity of the phase shifts induced in the two rhythms by identical light
      perturbations.

PMID- 16657684
TI  - Modification of the Period of a Noncircadian Rhythm in Nectria cinnabarina.
AB  - The sporulation rhythm in Nectria cinnabarina Tode ex Fr. is expressed by either
      concentric rings or spirals. The period is inversely proportional to the
      temperature and does not approach 24 hours; the rhythm is therefore noncircadian.
      The period of the zonation rhythm is lengthened by culturing the fungus on a
      dialysis membrane over the agar surface, on media solidified with an increased
      amount of agar, or on media containing deuterium oxide. These observations
      suggest that the transfer of materials by diffusion between the colony and the
      substrate is a significant factor in regulating the period of the rhythm.

PMID- 16657685
TI  - Photoactive Subunits of Protochlorophyll(ide) Holochrome.
AB  - A stable, soluble, and photoactive protochlorophyll(ide) complex has been
      extracted from dark-grown barley (Hordeum vulgare L.) leaves with buffer
      containing saponin and glycerol. After ammonium sulfate precipitation, the
      redissolved pigment complex was partially purified by chromatography on Sephadex
      gels in the presence of saponin. With the assumptions that the pigment complex
      from barley has the same shape and density as the proteins used for calibration,
      its molecular weight is 63,000. Photoactive protochlorophyll(ide) complex
      isolated from bean (Phaseolus vulgaris L.) and chromatographed by the same
      procedures has an aparent molecular weight of 100,000 or greater. No
      chromatographic separation of photoactive and inactive protochlorophyll(ide)
      complexes was observed. Photoconversion of protochlorophyll(ide) to
      chlorophyll(ide) did not change the chromatographic behavior of the pigment
      complex.The protochlorophyll(ide) complex had an absorption maximum at 644
      nanometers and a corresponding fluorescence emission maximum at 652 nanometers.
      Photoconversion yielded chlorophyll(ide) complex with an absorption maximum at
      678 nanometers and a main fluorescence emission maximum at 685 nanometers.
      Spectrofluorometry on partially photoconverted preparations gave no indication of
      energy transfer from protochlorophyll(ide) to chlorophyll(ide). This result is
      consistent with the presence of a single protochlorophyll(ide) molecule per
      active unit of the pigment complex.It is concluded that the protochlorophyll(ide)
      complex obtained from barley represents an active subunit of protochlorophyll
      holochrome.

PMID- 16657686
TI  - Effects of sucrose and kinetin on growth and chlorophyll synthesis in tobacco
      tissue cultures.
AB  - Investigations were carried out on the effects of various combinations of sucrose
      and kinetin concentrations on growth and chlorophyll production in a green and a
      nongreen clone of pith callus of Nicotiana tabacum L. It was found that 2
      milligrams per liter or higher amounts of kinetin induced greening in the
      nongreen tissue. The observations suggested that growth of the callus and
      synthesis of chlorophyll and soluble protein are controlled by relative
      concentrations of sucrose and kinetin in the medium. Kinetin was found to be
      inhibitory for chlorophyll synthesis in the green callus.

PMID- 16657687
TI  - Ethylene biosynthesis in fruit tissues.
AB  - Tracer studies with avocado tissues indicate that methionine is converted to
      ethylene at stages of the climacteric rise and the climacteric peak, but not at
      the preclimacteric stage. The results suggest that the control of ethylene
      biosynthesis is at a step after methionine is synthesized. The endogenous content
      of methionine was found to be so low that methionine must be actively turned over
      for ethylene biosynthesis during the stages when the rate of ethylene production
      is high. Oxygen was found to be essential for this conversion, indicating that at
      least one of the steps in conversion of methionine to ethylene is oxygen
      dependent. The ability of methionine and its keto analogue (alpha-keto-gamma
      methylthiobutyric acid) to serve as ethylene precursors by apple tissues was
      compared. Chemical and kinetic evidence support the view that methionine is a
      closer precursor of ethylene than its keto analogue.

PMID- 16657688
TI  - Reversible pH Changes in Cells of Chlamydomonas reinhardi Resulting from CO(2)
      Fixation in the Light and Its Evolution in the Dark.
AB  - Illumination of a suspension of Chlamydomonas reinhardi causes an increase in the
      pH of the medium which is reversed in the dark. This pH change is a manifestation
      of CO(2) uptake in the light and its evolution in the dark. Simultaneous
      measurements of pH changes and oxygen evolution reveal that the photosynthetic
      coefficient approaches one.Intact cells of F-60, a mutant strain of C. reinhardi
      that lacks an active phosphoribulokinase, do not exhibit the light-dependent pH
      increase or oxygen evolution. However, chloroplast fragments prepared from the
      cells of the mutant strain exhibit a normal "proton pump" activity.The light
      dependent pH increase shown by intact cells can be inhibited by KCN, by
      uncouplers of photosynthetic phosphorylation, and by Dio-9. It is markedly
      increased upon the addition of potassium bicarbonate, and all inhibitors tested
      inhibit the pH increase in both the presence and absence of potassium
      bicarbonate.The results of the present work negate the conclusion of other
      workers that the light-dependent pH changes in intact cells of C. reinhardi (and
      probably in other algae as well) are due to the operation of the "proton pump."

PMID- 16657689
TI  - Effect of the Hypocotyl Hook on Chlorophyll Accumulation in Excised Cotyledons of
      Cucumis sativus L.
AB  - Hypocotyl hooks have been shown to influence greening in excised cucumber
      (Cucumis sativus) cotyledons. The properties of the lag phase are greatly
      affected by the presence or absence of the hook tissue. A 45-second light
      pretreatment followed by 4 hours of darkness is sufficient to remove the lag
      phase from cotyledons with hooks, while hookless cotyledons require 2 hours of
      continuous illumination followed by 1 hour of dark incubation to break the lag
      phase. The effect of hooks on cotyledon greening is enhanced if the hooks are
      shielded from light. Cutting off the hooks after lag phase removal caused a
      marked decrease in chlorophyll accumulation in the cotyledons. These observations
      may indicate that the hypocotyl hooks produce a substance or substances needed in
      the greening process, which are translocated to the cotyledons. Indoleacetic
      acid, abscisic acid, gibberellin A(3), 6-benzylamino purine and delta
      aminolevulinic acid do not show any activity; on the other hand, ethylene appears
      to replace partially the hypocotyl hooks.

PMID- 16657690
TI  - Interaction of rubidium or sodium with potassium in absorption by intact sugar
      beet plants.
AB  - This study concerns the selective absorption of K and Rb or of K and Na by intact
      sugar beet (Beta vulgaris) plants from modified conventional nutrient solutions
      over an extended period of plant growth. Long term results agreed with those of
      short term experiments by other investigators using excised root systems and
      simple salt solutions. Potassium and Rb were mutually competitive in their
      absorption. High selectivity of K relative to Na absorption was observed. Sodium
      was excluded during the early growth period of sugar beets.

PMID- 16657691
TI  - Plants under Climatic Stress: I. Low Temperature, High Light Effects on
      Photosynthesis.
AB  - Photosynthetic rates of both C(4)- and C(3)-pathway plants grown at 25 C were
      measured before and during a period of chilling stress at 10 C, and then again at
      25 C following various periods at 10 C. When temperatures are first lowered
      photosynthetic rates drop immediately, then undergo a further reduction which is
      quite rapid in species such as Sorghum, maize, and Pennisetum; slower in soybean;
      and very slow in Paspalum and ryegrass. Visible light causes progressive
      permanent damage to the photosynthetic capacity of leaves during this period of
      lowered photosynthesis. The extent of damage increases with light intensity and
      the length of time leaves are held at 10 C but varies greatly between species,
      being roughly correlated with the extent to which chilling initially and
      subsequently lowers photosynthesis. Three days of chilling (10 C) at 170 w.m(-2)
      reduces the photosynthetic capacity of youngest-mature Paspalum leaves only 30 to
      40% while Sorghum leaves are essentially inoperative when returned to 25 C after
      the same stress. Root temperature has a substantial rapid effect on
      photosynthesis of soybean and little immediate effect on Sorghum. Photosynthesis
      of stress-intolerant species (Sorghum) is reduced only slightly more than that of
      semitolerant species (Paspalum) when temperatures are lowered at mid-photo
      period, but to a far greater extent if temperatures are reduced at the
      commencement of a photoperiod.

PMID- 16657692
TI  - Plants under Climatic Stress: II. Low Temperature, High Light Effects on
      Chloroplast Ultrastructure.
AB  - Mesophyll chloroplasts of the C(4)-pathway grasses Sorghum and Paspalum and of
      the C(3)-pathway legume soybean undergo ultrastructural changes under moderate
      light intensities (170 w.m(-2), 400-700 nanometers) at a tme when photosynthesis
      is much reduced by low temperature (10 C). The pattern of ultrastructural change
      was similar in these species, despite some differences in the initial sites of
      low temperature action on photosynthesis and differences in their mechanisms of
      CO(2) fixation. Starch grains in the chloroplasts rapidly reduce in size when
      chilling stress is applied. At or before the time starch grains completely
      disappear the membranes of the individual stromal thylakoids close together,
      reducing the intraspace between them while the chloroplast as a whole begins to
      swell. Extensive granal stacking appears to hold the thylakoids in position for
      some time, causing initial swelling to occur in the zone of the peripheral
      reticulum, when present. At more advanced stages of swelling the thylakoid system
      unravels while the thylakoid intraspaces dilate markedly. Initial thylakoid
      intraspace contraction is tentatively ascribed to an increase in the
      transmembrane hydrogen ion gradient causing movement of cations and undissociated
      organic acids from the thylakoid intraspace to the stroma. Chloroplast swelling
      may be caused by a hold-up of some osmotically active photosynthetic product in
      the chloroplast stroma. After granal unraveling and redilation of the thylakoid
      intraspaces, chloroplasts appear similar to those isolated in low salt hypotonic
      media. At the initial stages of stress-induced ultrastructural change, a marked
      gradient in degree of chloroplast swelling is seen within and between cells,
      being most pronounced near the surface of the leaf directly exposed to light.

PMID- 16657694
TI  - Fungus spore germination inhibited by blue and far red radiation.

PMID- 16657693
TI  - A Comparison of the Effects of Autoclaved and Nonautoclaved Gibberellic Acid on
      Lemna perpusilla 6746.

PMID- 16657695
TI  - Effect of sodium on potassium fluxes at the cell membrane and vacuole membrane of
      red beet.
AB  - Slices of red beet (Beta vulgaris) washed for 5 to 6 days are known to accumulate
      Na(+) in preference to K(+) from solutions containing both ions. The present
      work, using ion concentrations of 1.0 mm or less, with Ca(2+) added in some
      cases, shows that Na(+) strongly inhibits K(+) influx at the cell membrane
      (plasmalemma) while K(+) efflux is increased to a lesser extent. This result from
      compartmental analysis is confirmed by short (15-minute) influx experiments,
      which indicate an immediate inhibitory effect of Na(+) on K(+) influx at the cell
      membrane. It is concluded that cation selectivity, even when Na(+) is favored for
      uptake, is primarily determined at the cell membrane. Nevertheless, a high level
      of K(+) in the cytoplasm is maintained during Na(+) influx, by an inhibition of
      K(+) transfer to the vacuole.

PMID- 16657696
TI  - Development and Characteristics of Sodium-selective Transport in Red Beet.
AB  - Slices of storage tissue of red beet (Beta vulgaris L.) washed for only 1 day in
      distilled water readily absorb K(+) but lack a mechanism for rapid Na(+) uptake.
      A Na(+) transport mechanism develops if the tissue is washed for several days,
      and the tissue then excludes K(+) during Na(+) uptake.Both the high affinity and
      low affinity absorption mechanisms show a development of Na(+) transport with
      washing, and, in contrast to barley roots, cation selectivity in beet is not
      affected by the presence of calcium ions.K(+) and Na(+) do not appear to compete
      for binding sites at the surface of the cells, but, as in barley roots, the
      cations compete in some way for electrically balancing transported ions.
      Nevertheless, the development of Na(+) transport and the interaction of Na(+)
      with K(+) occur in the same way whether cation transport is balanced by Cl(-)
      uptake or by H(+) or HCO(3) (-) transport.

PMID- 16657697
TI  - Solubilization and Separation of Uridine Diphospho-d-glucose: beta-(1 --> 4)
      Glucan and Uridine Diphospho-d-glucose:beta-(1 --> 3) Glucan Glucosyltransferases
      from Coleoptiles of Avena sativa.
AB  - The particulate glucan synthetase preparation isolated from a homogenate of oat
      coleoptiles at 4 C lost 65% of its original activity after 1 day when the UDP-d
      glucose substrate concentration was 5 x 10(-7)m to 1.0 x 10(-6)m. Storage of the
      particulate enzyme at -20 C or in liquid nitrogen did not prevent the enzyme from
      losing its activity. Incorporation of 0.5% hovine serum albumin into the medium
      stabilized the particulate enzyme at 0 C for 6 days and for at least 2 weeks in
      liquid nitrogen.When the particulate enzyme was treated with 8% digitonin, 40 to
      50% of its activity appeared in the 100,000g supernatant fraction. The
      particulate and digitonin-solubilized enzyme preparations synthesized both beta
      (1 --> 4) and beta-(1 --> 3) glucosyl linkages from UDP-d-glucose, but beta-(1 -
      > 3) glucan was the main product at 1 x 10(-3)m UDP-d-glucose substrate. The
      activity of beta-(1 --> 4) glucan synthetase was stimulated at least 10-fold in
      the presence of MgCl(2). A separation of beta-(1 --> 4) and beta-(1 --> 3) glucan
      synthetase activities could be achieved at 1 x 10(-3)m UDP-d-glucose when the
      digitonin-solubilized enzyme was adsorbed on a hydroxylapatite gel and then
      eluted with concentrated potassium phosphate buffer. The results indicate that
      the particulate enzyme contains two enzymes, one responsible for the synthesis of
      beta-(1 --> 4) and another beta-(1 --> 3) linkages in the glucan or glucans
      synthesized from UDP-d-glucose.

PMID- 16657698
TI  - Changes in Sterol Composition during Greening of Etiolated Barley Shoots.
AB  - THE FOLLOWING STEROLS WERE IDENTIFIED IN BARLEY SHOOTS: stigmasterol, beta
      sitosterol, campesterol, and cholesterol. The total sterol content of green and
      etiolated tissue was 2.84 and 3.20 milligrams per gram dry weight, respectively.
      The free sterols accounted for most of the difference in total sterol content.
      The sterol ester, sterol glycoside, and acylated sterol glycoside contents of
      green and etiolated barley shoots were essentially the same. Etiolated tissue had
      twice as much total beta-sitosterol as stigmasterol, while green tissue had equal
      amounts of these two sterols. The campesterol and cholesterol content was the
      same in green and etiolated tissue. This same sterol composition pattern held
      true for the free, glycosidic, and acylated glycosidic sterols; however, the
      sterol ester fraction had a completely different composition pattern. The
      esterified stigmasterol content was quite low in green and etiolated tissue, and
      campesterol was the second largest esterfied sterol component in etiolated
      tissue. Etiolated barley seedlings exposed to light had a shift in the ratio of
      free stigmasterol to beta-sitosterol in favor of stigmasterol; however, no
      correlation was observed between chlorophyll synthesis and shift in sterol
      composition.

PMID- 16657699
TI  - Poly-beta-hydroxybutyrate Utilization by Soybean (Glycine max Merr.) Nodules and
      Assessment of Its Role in Maintenance of Nitrogenase Activity.
AB  - Soybean (Glycine max) nodule bacteroids contain high concentrations of poly-beta
      hydroxybutyrate and possess a depolymerase system that catalyzes the hydrolysis
      of the polymer. Changes in poly-beta-hydroxybutyrate content and in activities of
      nitrogenase, beta-hydroxybutyrate dehydrogenase, and isocitrate lyase in nodule
      bacteroids were investigated under conditions in which the supply of carbohydrate
      from the soybean plants was interrupted. The poly-beta-hydroxybutyrate content of
      bacteroids did not decrease appreciably until the carbohydrate supply from the
      host plants was limited by incubation of excised nodules, incubation of plants in
      the dark, or by senescence of the host plant. Isocitrate lyase activity in
      bacteroids was not detected until poly-beta-hydroxybutyrate utilization appeared
      to begin. The presence of a supply of poly-beta-hydroxybutyrate in nodule
      bacteroids was not sufficient for maintenance of high nitrogenase activity under
      conditions of limited carbohydrate supply from the host plant. An unusually high
      activity of beta-hydroxybutyrate dehydrogenase was observed in bacteroid extracts
      but no significant change in the activity of this enzyme was observed as a result
      of apparent utilization of poly-beta-hydroxybutyrate by nodule bacteroids.

PMID- 16657700
TI  - The physical basis of gravity stimulus nullification by clinostat rotation.
AB  - The question of how rotation on a horizontal axis clinostat removes plants from
      the influence of the gravitational stimulus is answered. It is shown that
      appropriate horizontal axis clinostat rotation restricts the fall of
      intracellular particles to a quasi-circular path such that the position of the
      particle remains virtually stationary within cells. The displacement of the path
      of fall, due to centrifugal force, is then considered, and a method of
      determining the optimal rotation rate is developed from physical principles. This
      method selects the rotation rate which minimizes the volume of cytoplasm through
      which particles pass under the joint influence of centrifugal and gravitational
      forces. With the recognition that single axis clinostats are ineffective with
      large plants or for long experiments, a new type of clinostat is proposed on
      which intracellular conditions can be rendered virtually identical to those of
      plants in satellite free fall regardless of plant size or duration of
      experiment.It is shown that most low gravity biological responses can be studied
      using clinostats with only occasional satellite free fall experiments for
      verification. It is further inferred that most of these responses can be
      effectively and economically studied by computer simulation.

PMID- 16657701
TI  - Ethylene-enhanced Synthesis of Phenylalanine Ammonia-Lyase in Pea Seedlings.
AB  - The effect of ethylene on the development of phenylalanine ammonia-lyase activity
      in segments excised from the epicotyl apex of pea seedling was studied. Although
      there was some increase in phenylalanine ammonia-lyase activity in segments not
      treated with ethylene, a marked increase in phenylalanine ammonia-lyase activity
      occurred in ethylene-treated tissues during the incubation. The induction period
      was estimated to be about 6 hours. The activity reached a maxmum at 30 hours and
      then declined. On withdrawal of ethylene, the increase was sustained for a short
      period and then stopped. After retreatment with ethylene, the increase was
      resumed. Addition of CO(2) reduced the effect of ethylene. Administration of
      cycloheximide or actinomycin D at an early period almost completely suppressed
      the increase in phenylalanine ammonia-lyase activity. However, if these
      inhibitors were administered at a later period, while phenylalanine ammonia-lyase
      activity was approaching a maximum, they not only failed to reduce but rather
      stimulated the activity. These results are consistent with the view that there
      exist both phenylalanine ammonia-lyase-synthesizing and -inactivating systems,
      and that the development of both systems may involve de novo synthesis of
      protein.

PMID- 16657702
TI  - Effects of gamma irradiation on chromatin activity of sugar beet tissue.
AB  - Chromatin-associated RNA polymerase activity increases during washing of sugar
      beet tissue to a maximum by 20 hours. This increase was inhibited by dosages of
      gamma irradiation between 50 and 400 krad. Template availability, as measured by
      saturating levels of added Escherichia coli RNA polymerase, also increased with
      washing and was inhibited, although to a lesser extent, by the above irradiation
      dosages. Neither endogenous polymerase activity nor template availability was
      affected by high dosages (300 krad) in unwashed tissue. Exposure of tissue to
      irradiation (300 krad) at different times during a 20-hour washing period
      severely inhibited the development of RNA polymerase activity during the early
      stages of washing. The inhibition of template availability, however, was
      independent of time of irradiation. The data presented are discussed in relation
      to the mechanisms involved in the inhibitory effects of gamma irradiation on RNA
      production and subsequent protein synthesis.

PMID- 16657703
TI  - Spectral Distribution of Light in a Tobacco Canopy and Effects of End-of-Day
      Light Quality on Growth and Development.
AB  - Shifts in spectral distribution of light were determined within and below a
      canopy of field-grown burley tobacco (Nicotiana tabacum L. cv. Burley 21). The
      leaves transmitted much far red light relative to red and blue light. Thus,
      shaded leaves received more far red light, relative to red and blue, than was
      received by unshaded leaves. Under field conditions, tobacco plants within rows
      grew taller than did those at the west end of rows.Developmental effects of end
      of-day red and far red light were studied in the controlled environment
      laboratory. Plants that received far red light last, each day, resembled plants
      shaded by other plants. The far red-irradiated plants developed longer
      internodes, were lighter green in color, and had thinner leaves than the red
      irradiated ones. Plants of both treatments had the same number of leaves on the
      main axis. However, the red-irradiated plants developed branches from axils of
      lower leaves, while no branching occurred on plants that received far red
      radiation last each day.

PMID- 16657704
TI  - The Effect of pH on the Products of Photosynthesis in CO(2) by Chloroplast
      Preparations from Acetabularia mediterranea.
AB  - The effect of pH on the pathways of carbon in photosynthesis was examined in
      chloroplast preparations from Acetabularia mediterranea. The flow of carbon into
      a number of photosynthetic intermediates, particularly sucrose, glycine, serine,
      glycolate, and the insoluble fraction, was strongly influenced by pH. At higher
      pH a much larger portion of the (14)C entered intermediates of the glycolate
      pathway. Although maximal apparent photosynthesis occurred at pH 7.6 to 7.7,
      cytoplasmic pH was found to be 8.0 to 8.4, using indicators. The pattern of
      distribution of (14)C in intermediates of whole cells was closest to that in
      chloroplasts at the higher pH range.

PMID- 16657705
TI  - Participation of Long-Day Inhibition in Flowering of Xanthium strumarium L.
AB  - Two basic experiments defined a long-day inhibitory effect on Xanthium flowering:
      the basal half of a single leaf on long day inhibits response of the tip half to
      a short day; and a long-day leaf inhibits response of a short-day leaf, providing
      it is between the short-day leaf and a receptive bud (whether above or below the
      short-day leaf). Five hypotheses were explored with the conclusions that the tip
      half can synthesize florigen, and inhibition is not due to prevention of florigen
      synthesis, translocational effects, or a translocatable long-day inhibitor.
      Inhibition is localized and may be a condition of the leaf or a relatively
      immobile substance. Studies of critical dark period, light intensity, and
      interruption of a dark period show that, when the leaf is not producing florigen,
      it is actively inhibitory. Immature leaves are more inhibitory than older leaves.
      The effect was found not to pass dead tissue, and iron-deficient tissue will
      cause inhibition, though it will not cause promotion.

PMID- 16657706
TI  - Intact tissue assay for nitrite reductase in barley aleurone layers.
AB  - A method has been devised for the detection and measurement of nitrite reductase
      activity in intact barley (Hordeum vulgare L. cv. Himalaya) aleurone layers. The
      technique involves feeding aleurone layers nitrite and measuring nitrite
      disappearance after a given time period. The method also allows simultaneous
      determination of nitrite uptake by the tissue. Quantitative recovery of nitrite
      is obtained by rapid heating of tissue in the presence of dimethyl
      sulfoxide.Using the procedure described, nitrite reductase activity in intact
      barley aleurone layers was determined. Enzyme activity was increased by prior
      incubation of the tissue with nitrate, but considerable activity was present in
      tissue incubated without nitrate. Nitrate-induced activity was inhibited by
      cycloheximide but not by actinomycin D. Enzyme activity in induced layers was
      inhibited by 2,4-dinitrophenol, and partially by antimycin A and 2-n-heptyl-4
      hydroxyquinoline N-oxide. Activity in noninduced tissue appeared to be less
      sensitive to these respiratory inhibitors. In contrast, both activities were
      inhibited more than 90% by anaerobiosis; but nitrate-induced and noninduced
      aleurone layers were able to reduce nitrite anaerobically when the concentration
      of substrate in the assay medium was reduced from 250 mum to 25 mum. Nitrite
      uptake was relatively insensitive to anaerobiosis and to the inhibitors
      tested.Nitrite depletion from the medium by aleurone layers was rapid at pH 4.5
      and negligible at pH 7.5. Nitrite accumulated at pH 4.5 under anaerobic
      conditions was rapidly released when the tissue was transferred to medium at pH
      7.5. Nitrite release at pH 7.5 occurred whether the tissue was maintained under
      anaerobic or aerobic conditions.

PMID- 16657707
TI  - The influence of auxin, cacodylic Acid, and amitrole on the abscission of petiole
      explants.
AB  - The influence of indoleacetic acid, cacodylic acid (hydroxy-dimethylarsine
      oxide), and amitrole (3-amino-1,2,4-triazole) on the petiole explant abscission
      rate was studied in three species. Indoleacetic acid increased the abscission
      rate in both bean (Phaseolus vulgaris L. var. Red Kidney) and Coleus (Coleus
      blumei Benth) at 10(-3) and 10(-4)m but had no effect on abscission in privet
      (Ligustrum ovalifolium). Cacodylic acid was found to stimulate abscission in
      explants of beans and privet, but not in Coleus. Amitrole did not stimulate
      abscission under any circumstance tested. In no case was the abscission rate
      dependent on the time at which any of the chemicals was applied. These data do
      not support the two-phase response of explants to applied auxin.

PMID- 16657708
TI  - Calcium Deficiency of Dark-grown Seedlings of Phaseolus vulgaris L.
AB  - Hypocotyl collapse in dark-grown seedlings of Phaseolus vulgaris cv. Pinto was
      due to calcium deficiency. There was no evidence of an associated pathogen. The
      number of seedlings with hypocotyl collapse decreased and the mean hypocotyl
      length increased when increasing levels of calcium (0-100 micrograms per gram)
      were supplied in an external nutrient solution to seedlings grown under sterile
      conditions.When seedlings were supplied with a complete nutrient solution,
      containing calcium at 100 micrograms per gram, but minus potassium, magnesium,
      sulfur, nitrogen, or phosphorus, occasional plants developed hypocotyl collapse
      symptoms; however, the lengths of hypocotyls varied little from those of controls
      grown in complete nutrient. When the calcium level in the deficient nutrient
      solutions was raised to 200 micrograms per gram, the number of plants with
      hypocotyl collapse was reduced markedly.With complete nutrient solution minus
      calcium, seedlings developed symptoms of calcium deficiency irrespective of seed
      size, i.e., irrespective of whether or not the seed contained a total calcium
      content that was low or relatively high.An increase in hypocotyl length in
      response to an external supply of calcium was obtained with five cultivars of
      Phaseolus vulgaris L. and with one of Soja max Piper. A similar response to
      calcium was obtained for epicotyl growth of a cultivar of Vicia faba L., but not
      for a cultivar of Pisum sativum L.

PMID- 16657709
TI  - The mechanical behavior of isolated Avena coleoptile walls subjected to constant
      stress: properties and relation to cell elongation.
AB  - In order to assess the role of the mechanical properties of the wall in auxin
      induced cell elongation, a study has been made of the ability of isolated Avena
      coleoptile walls to extend (creep) when subjected to a constant applied stress.
      Creep occurs as a viscoelastic extension which has the following characteristics:
      the extension is proportional to log time and is partly reversible, and the
      extension rate has a Q(10) of about 1.05 and is markedly greater in auxin
      pretreated walls. In nonconditioned walls the extension rate is proportional to
      applied stress, but pre-extension causes the appearance of an apparent yield
      strain. The similarity of creep and instantaneous plastic deformation in response
      to temperature or to pretreatment with auxin or KCN suggests that the
      instantaneous deformation is simply the viscoelastic extension which occurs at
      very short times. A comparison of these viscoelastic properties with the
      properties of auxin-induced cell elongation indicates that cell elongation
      requires more than just a physical extension of the wall. It is suggested that
      elongation occurs as a series of extension steps, each of which involves a
      viscoelastic extension preceded or accompanied by an auxin-dependent biochemical
      change in the wall properties.

PMID- 16657710
TI  - The effect of auxin on stress relaxation in isolated Avena coleoptiles.
AB  - In order to characterize further the mechanical properties of coleoptile cell
      walls, stress relaxation measurements were made on methanol-boiled sections of
      Avena coleoptiles. Relaxation was measured both in mechanically conditioned
      specimens and in specimens which had not been previously extended. In both cases
      the relaxation was proportional to log time. Mechanical conditioning increased
      the relaxation modules and decreased the relative rate of relaxation. In
      contrast, pretreatment of the live coleoptiles with indoleacetic acid reduced the
      relaxation modulus and the absolute rate of relaxation but did not affect the
      relative rate of relaxation. Essentially similar pictures of the mechanical
      properties of coleoptile walls are obtained from stress relaxation and creep
      tests; the wall behaves as a nonlinear viscoelastic material.

PMID- 16657711
TI  - Recovery of photosynthesis in sunflower after a period of low leaf water
      potential.
AB  - Photosynthesis was studied in sunflower plants subjected to 1 to 2 days of
      desiccation and then permitted to recover. The leaf water potential to which
      leaves returned after rewatering was dependent on the severity of desiccation and
      the evaporative conditions. Under moderately evaporative conditions, leaf water
      potential returned to predesiccation levels after 3 to 5 hours when desiccation
      was slight. Leaf water potentials remained below predesiccation levels for
      several days after rewatering when leaf water potentials decreased to -13 to -19
      bars during desiccation. Leaf water potential showed no sign of recovery when
      leaf water potentials decreased to -20 bars or below during desiccation. The lack
      of full recovery of leaf water potential was attributable to increased resistance
      to water transport in the roots and stem. The resistance ultimately became large
      enough to result in death of the leaves because net water loss continued even
      after the soil had been rewatered.Measurements of photosynthesis were made at
      high light intensities, where stomatal aperture often affects photosynthesis, and
      at low light intensities, where the photochemical activity of the leaves limits
      photosynthesis. Providing leaf water potentials remained above -12 bars during
      the desiccation period and returned to predesiccation levels during recovery,
      photosynthesis under both low and high light paralleled the recovery in leaf
      water potential after rewatering. After desiccation to leaf water potentials
      below -12 bars, recovery was incomplete under high light and could be attributed
      to lack of full stomatal opening. Lack of full opening persisted for 3 days and
      showed no sign of eventual recovery even though leaf water potentials recovered
      fully. Under low light, however, recovery in photochemical activity was complete
      within 15 hours after desiccation to leaf water potentials as low as -17 bars.

PMID- 16657712
TI  - Effects of photoperiod on growth rate and endogenous gibberellins in the long-day
      rosette plant spinach.
AB  - The earliest visible responses of spinach plants (Spinacia oleracea L., cv. Savoy
      Hybrid 612) transferred from short to long days (8 hours of high intensity light
      supplemented with 16 hours of low intensity illumination from incandescent lamps)
      were upright leaf orientation and increased elongation of the petioles. The
      effect of long days on growth rate was direct; i.e., there was no after-effect if
      the plants were transferred to short days. Gibberellin A(3) applied to plants
      under short days had an effect similar to that of long days, whereas application
      of the growth retardant AMO-1618 [2'-isopropyl-4'-(trimethylammonium chloride)-5'
      methylphenyl piperidinel-carboxylate] under long days caused a growth habit
      typical of short-day conditions. Gibberellin A(3) caused more stem growth in
      plants under long days in which the endogenous gibberellin content had been
      reduced by AMO-1618 than in plants under short days not treated with the growth
      retardant.Three gibberellin-like substances, called I, II, and III in order of
      increasing R(F) value, were present in acidic extracts of spinach under short
      days. After transfer to long days, II increased, whereas I and III decreased, the
      latter below the level of detection in the d5 corn assay. Following application
      of AMO-1618 the gibberellin content of plants under long days fell off more
      rapidly than in those under short days, indicating that gibberellin turnover was
      markedly higher under long days. This increased rate of gibberellin metabolism
      was established after 2 long days. When plants were returned to short days, the
      turnover of gibberellins declined. It is suggested that a higher rate of
      gibberellin biosynthesis combined with increased sensitivity to gibberellin is
      responsible for the observed growth responses in spinach under long days.

PMID- 16657713
TI  - Effects of water stress on the activities of three enzymes in maize seedlings.
AB  - Changes in the activities of three enzymes (nitrate reductase, l-phenylalanine
      ammonia-lyase, and a dehydronicotinamide adenine dinucleotide-oxidase complex)
      were measured during development of water stress in young maize (Zea mays)
      plants.l-Phenylalanine ammonia-lyase and nitrate reductase activities decreased
      markedly with water deficits of 10 to 20%. The activities did not reach zero at
      water deficits as high as 50%, but appeared to approach a new steady state.
      Partial to complete recovery of enzyme activity occurred 24 hours after
      rehydration of the stressed plants. The oxidase activity did not respond to water
      stress in the same manner as that of the other two enzymes.It is suggested that
      the level of enzyme activity is a consequence of an equilibrium between the rates
      of synthesis and degradation, and that progressive tissue dehydration reduces
      both the enzyme synthesis and the enzyme-inactivating systems.

PMID- 16657714
TI  - The effect of calcium and inhibitors on corn mitochondrial respiration.
AB  - The effects of KCN, antimycin A, malonate, rotenone, and amytal on the oxidation
      of malate, succinate, and extramitochondrial reduced nicotinamide adenosine
      dinucleotide (NADH) by corn mitochondria were studied. Potassium cyanide and
      antimycin A inhibited the oxidation of all three substrates. Rotenone and amytal
      inhibited only the oxidation of malate, and malonate inhibited only the oxidation
      of succinate. Rotenone, amytal, and malonate did not inhibit the oxidation of
      extramitochondrial NADH. The calcium stimulation of the oxidation of
      extramitochondrial NADH was prevented by KCN and antimycin A but not by amytal,
      rotenone, or malonate. It is suggested that corn mitochondria possess a
      flavoprotein specific for extramitochondrial NADH and that this flavoprotein is
      sensitive to divalent cations.

PMID- 16657715
TI  - Effect of iron on the transport of citrate into the xylem of soybeans and
      tomatoes.
AB  - Iron transport in soybeans (Glycine max [L] Merr.) and tomatoes (Lycopersicum
      esculentum) is controlled by factors that are altered manyfold as the plant
      experiences an iron stress (deficiency). Depending on their response to an Fe
      stress, plants in this study are classed (a) Fe-inefficient or (b) Fe-efficient.
      The Fe-efficient plants transport more Fe and concomitantly more citrate than the
      Fe-inefficient plants.An available supply of Fe added to the plant root will
      facilitate the release of citrate to the stem exudate in both soybeans and
      tomatoes. Also, when the iron supply is decreased by trapping Fe(2+) at the root,
      Fe transport decreases with a concomitant decrease of citrate in the stem
      exudate. Factors other than citrate appear to affect movement of Fe from the
      external solution into root cells where Fe is chelated with citrate and moves
      thereafter as Fe citrate. This makes some of the citrate that is transported in
      the stem exudate dependent on the amount of Fe made available at the root.

PMID- 16657716
TI  - Effect of Light on the Rate of Glycolysis in Scenedesmus obliquus.
AB  - The production of d-lactic acid, a major fermentation product of Scenedesmus
      obliquus strain D(3), is inhibited by light. This inhibition has been observed in
      the wild type as well as in Bishop's mutant 11. However, in mutant 8, which lacks
      photophosphorylation, light stimulated the formation of d-lactic acid.

PMID- 16657717
TI  - Promotion of callus formation by abscisic Acid in citrus bud cultures.

PMID- 16657718
TI  - CO(2) Compensation Concentration in Maize (Zea mays L.) Genotypes.

PMID- 16657719
TI  - Abnormal Stomatal Behavior and Hormonal Imbalance in Flacca, a Wilty Mutant of
      Tomato: III. Hormonal Effects on the Water Status in the Plant.

PMID- 16657721
TI  - Phytochrome Control of Germination of the Spores of Asplenium nidus.

PMID- 16657720
TI  - Inhibition of ethylene production by rhizobitoxine.
AB  - Rhizobitoxine, an inhibitor of methionine biosynthesis in Salmonella typhimurium,
      inhibited ethylene production about 75% in light-grown sorghum seedlings and in
      senescent apple tissue. Ethylene production stimulated by indoleacetic acid and
      kinetin in sorghum was similarly inhibited. With both apple and sorghum, the
      inhibition could only be partially relieved by additions of methionine. A
      methionine analogue, alpha-keto-gamma-methylthiobutyric acid, which has been
      suggested as an intermediate between methionine and ethylene, had no effect on
      the inhibition.Incorporation of (14)C from added methionine-(14)C into ethylene
      was curtailed by rhizobitoxine to about the same extent as was ethylene
      production. These results suggest that rhizobitoxine interferes with ethylene
      biosynthesis by blocking the conversion of methionine to ethylene and not
      indirectly by inhibiting the biosynthesis of methionine. Ethylene production by
      Penicillium digitatum, a fungus which produces ethylene via pathways not
      utilizing methionine as a precursor, was not affected by rhizobitoxine.

PMID- 16657722
TI  - Abscisic Acid raises the permeability of plant cells to water.

PMID- 16657723
TI  - Comparison of pressure chamber and thermocouple psychrometer determinations of
      leaf water status in tomato.

PMID- 16657724
TI  - Amperometric measurement of hydrogen evolution in chlamydomonas.

PMID- 16657725
TI  - Metabolism of Separated Leaf Cells: II. Uptake and Incorporation of Protein and
      Ribonucleic Acid Precursors by Tobacco Cells.
AB  - Enzymatically separated tobacco leaf cells took up amino acids, uracil, and
      uridine from the incubation medium and incorporated them into proteins and RNA,
      respectively, at a linear rate for approximately 30 hours. Both uptake and
      incorporation were light-dependent, although cells prepared from preilluminated
      plants or preillumination of cells allowed some uptake and incorporation to occur
      in the dark. The light was necessary to satisfy a photosynthetic requirement, but
      could be replaced in part by ATP in the medium.Several lines of evidence support
      the conclusion that the rate of uptake of amino acids, uracil, and uridine was
      dependent upon the subsequent incorporation of these compounds into
      macromolecules.

PMID- 16657726
TI  - Isolation and characterization of polyphenol oxidase isozymes of clingstone
      peach.
AB  - The polyphenol oxidase system in clingstone peach (Prunus persica) was
      investigated. Polyacrylamide disc-gel electrophoresis indicated four bands with
      polyphenol oxidase activity in extracts from acetone powder of clingstone peach.
      These four isozymes were then isolated from a buffer extract of peach acetone
      powder by cold acetone precipitation, followed by diethylaminoethyl cellulose
      column chromatography. All isozymes had different heat stabilities. At 55 C,
      polyphenol oxidases A, B, and D had half-lives of 5.4, 14.6, and 14.1 minutes,
      respectively. Polyphenol oxidase C was stable over a period of 50 minutes of
      incubation at 55 C, but had a half-life of 2.2 minutes at 76 C. None of the
      isozymes had monophenolase activity, and they varied in their specificity for
      several diphenols. The following values were found for polyphenol oxidases A, B,
      C, and D, respectively, with catechol as substrate: optimal pH: 6.8, 6.5, 7.2,
      and 7.0; Michaelis constant: 6.6, 4.2, 7.0, and 36 mm; V(max)/(E(0)): 4.95, 39.4,
      2.16, and 80.0 (DeltaA min(-1) mg(-1)). Each isozyme showed a different amount of
      inhibition by NaHSO(3), NaCl, NaCN, l-ascorbic acid, glutathione,
      ethylenediaminetetraacetate, and sodium diethyldithiocarbamate.

PMID- 16657727
TI  - Effect of Phloroglucinol and Resorcinol on the Clingstone Peach Polyphenol
      Oxidase-catalyzed Oxidation of 4-Methylcatechol.
AB  - Phloroglucinol and resorcinol are not substrates for clingstone peach (Prunus
      persica) polyphenol oxidase, but they react with 4-methyl-o-quinone, produced
      either enzymatically or nonenzymatically, to give an intense red or red-brown
      color with a maximal absorption at about 470 nanometers. Several colored products
      were isolated from an ethyl acetate extract of the reaction by two-dimensional
      thin layer chromatography. Based on thin layer chromatographic and spectral
      studies of the enzymatic and nonenzymatic reactions, polyphenol oxidase does not
      play a role in the reaction between 4-methyl-o-quinone and phloroglucinol,
      resorcinol, d-catechin, or orcinol. In such reactions, the function of polyphenol
      oxidase is the formation of 4-methyl-o-quinone which then reacts nonenzymatically
      with the above phenols. Activation energies of both enzymatic and nonenzymatic
      reactions were determined.

PMID- 16657728
TI  - Regulation of Bud Rest in Tubers of Potato, Solanum tuberosum L: VIII. Early
      Effects of Gibberellin A(3) and Abscisic Acid on Ultrastructure.
AB  - Using the electron microscope, we compared the effects of abscisic acid and
      gibberellin A(3) on excised buds from resting potato (Solanum tuberosum L.)
      tubers. Cells of abscisic acid-treated buds became progressively more vacuolated
      during a 12-hour time course study as compared with control (water) and
      gibberellin A(3)-treated buds. Concentric configurations of endoplasmic reticulum
      were present in apical cells of freshly excised buds. After about 6 hours these
      configurations began to open and disperse, and after 12 hours, intact concentric
      configurations were no longer evident. Both abscisic acid and gibberellin A(3)
      induced opening and dispersal of the concentric configurations, sometimes as
      early as 0.5 hour after excision and treatment with hormones.

PMID- 16657729
TI  - Growth Inhibition and Metabolite Pool Levels in Plant Tissues Fed d-Glucosamine
      and d-Galactose.
AB  - The growth of corn (Zea mays) roots and barley (Hordeum vulgare) coleoptiles is
      sensitive to the presence of external d-glucosamine and d-galactose. In order to
      investigate this effect, tissues were fed the radioactive monosaccharides at
      concentrations that ranged from those that were strongly inhibitory to those that
      had little influence on growth. At low concentrations, d-glucosamine is converted
      to uridine diphosphate-N-acetyl-d-glucosamine, phosphate esters of N
      acetylglucosamine, and free N-acetylglucosamine. As the external concentrations
      were increased, the pool levels of each of these metabolites rose several fold;
      and, in corn roots, two unidentified compounds, which had not been detected
      previously, began to accumulate in the tissues. The major products of d-galactose
      metabolism were uridine diphosphate-d-galactose and d-galactose 1-phosphate at
      all the concentrations tested. Both these compounds showed a marked increase as
      the external galactose concentrations were raised to inhibitory levels. The
      experiments indicate that efficient pathways exist in plants for the metabolism
      of d-glucosamine and d-galactose. These pathways, however, do not appear to be
      under strict control, so that metabolites accumulate in unusually high amounts
      and presumably interfere competitively with normal carbohydrate metabolism.

PMID- 16657730
TI  - Enhanced deoxyribonucleic Acid polymerase activity of chromatin from soybean
      hypocotyls treated with 2,4-dichlorophenoxyacetic Acid.
AB  - Chromatin isolated from soybean (Glycine max L., var. Wayne) hypocotyls was
      capable of catalyzing the polymerization of labeled deoxyribonucleoside
      triphosphate in the presence of the three other deoxyribonucleoside triphosphates
      into a trichloroacetic acid-insoluble product. This product was insensitive to
      base hydrolysis and ribonuclease, but was sensitive to acid hydrolysis and
      deoxyribonuclease. Chromatin-DNA polymerase required Mg(2+) and all four
      deoxyribonucleoside triphosphates for maximal activity. Inorganic pyrophosphate
      and actinomycin D inhibited the polymerase activity, but 2, 4
      dichlorophenoxyacetic acid had no effect in vitro. Chromatin from plants
      previously treated with 2, 4-dichlorophenoxyacetic acid supported a greater level
      of DNA synthesis than did chromatin from untreated plants.